PMID- 27652724 TI - Mixed response to initiatives. AB - Health care unions gave a mixed reponse to the Government's Citizen's Charter and the announcement that a Patient's Charter will be launched in September. PMID- 27652723 TI - ? AB - Young at heart: Derrick Morris, the longest surviving heart transplant patient in Europe and skin transplant patient Ferrial Sycd pictured at the launch of National Transplant Week at St Mary's Hospital. Paddington, last week. PMID- 27652725 TI - NVQs. AB - The Department of Health's decision to go ahead with its National Vocational Qualifications for care workers has been welcomed by nursing unions. PMID- 27652726 TI - ? AB - First course: About 20 Oxford nurses were recently presented with their certificates after attending the first ever resource management course, organised jointly by the Royal College of Nursing and Oxford Regional Health Authority . PMID- 27652727 TI - Survey reveals major gaps in nurse education. AB - Urgent action is needed to improve some nurses' knowledge of HIV and AIDS, according to a major new survey. PMID- 27652728 TI - New appointments. AB - Jennette Golding is the new RCN North Hast Thames Senior Officer. PMID- 27652729 TI - Nurses pay for vandalised cars. AB - Community midwives at Guy's Hospital say they are having to pay up to L150 a month towards the cost of repairs to lease cars vandalised while they are on duty. PMID- 27652731 TI - Forum told Standards are 'practically useless'. AB - Standards have taken the 'academically respectable and practically useless' role previously filled by the 'Nursing Process', a speaker told the RCN's General Managers' Forum Conference last week. PMID- 27652730 TI - Obituary. AB - The Royal College of Nursing has paid tribute to Jack Steinberg, who died recently. He was benefactor of the Steinberg nursing research collection at the RCN library. A businessman, Mr Steinberg was Chair of both the King's College Hospital Research Trust and the King's Medical Research Trust. PMID- 27652732 TI - ? AB - Norma Major, left, joined the Prime Minister at a topping out' ceremony for the third phase of the rebuilding programme at Guy's Hospital in London. PMID- 27652734 TI - Nurses condemn'alarmist' POA reaction to escape. AB - The Prison Officers' Association at Broadmoor Hospital has been criticised for making 'inflammatory statements' after an escape from the hospital. PMID- 27652733 TI - Audit commission. AB - An Audit Commission report due out in October is likely to recommend that nurse management needs to become leaner and more clinically based while maintaining a role at the highest levels in the health service. PMID- 27652735 TI - Care of the elderly. AB - The King's Fund Grants Committee has set aside L400,000 to improve services for elderly people. Applications for a share of the money are invited from any organisation which is either a commissioner or provider of such services. PMID- 27652736 TI - ? AB - Art transplant: An exhibition of paintings by Addenbrooke's surgeon Sir Roy Caine opened last week at the Barbican to coincide with National Transplant Week. Robert Blades, pictured, was one of the patients at the launch. PMID- 27652737 TI - RCN welcomes guidelines for minimum standards. AB - A minimum of two registered sick children's nurses should be on duty at all times in hospital paediatric departments and wards, new Department of Health guidelines on the 'Welfare of children and young people in hospital' recommend. PMID- 27652739 TI - Parliament. AB - Theft, fraud and arson cost the NHS in England over L3.4 million last year, Junior Health Minister Stephen Dorrell told the all-party select committee on health last week. PMID- 27652740 TI - ? AB - In focus: Nursing Standard Editor, Norah Casey, second left, hosted a reception in Cambridge to launch our East Anglian Focus. PMID- 27652741 TI - UK should be leaders in European mental health. AB - British psychiatric nurses should be at the forefront of nursing initiatives as European nations prepare for the development of an open market in 1992, it was claimed last week. PMID- 27652743 TI - Call to earmark education money. AB - Midwives are demanding health authorities earmark cash for their continuing education and professional development. PMID- 27652742 TI - ? AB - RCM President Margaret Brain announced plans to launch a 'Midwives Manifesto' prior to the General Election to motivate midwives to lobby local candidates on policies which will affect women. Any party wishing to form a new Government must have women's issues at the forefront of their manifesto if they are to succeed,' she said, warning delegates that now is the time for us to be setting out our wares'. PMID- 27652744 TI - Delegates oppose more responsibility for HCAs. AB - Proposals to give health care assistants more responsibility in midwifery units were opposed by delegates. PMID- 27652746 TI - Cash available for NDUs. AB - Nurses are being encouraged to apply for funds to establish Nursing Development Units by junior health minister, Stephen Dorrell. He was speaking at a Department of Health/London post-graduate teaching hospitals' conference organised by Nursing Standard. PMID- 27652745 TI - Vote to delay reforms. AB - National Health Service reforms should be put on hold until the Trusts approved this year are fully evaluated, delegates agreed. PMID- 27652747 TI - Excellence in contemporary clinical nursing. AB - Chief Nursing Officer Anne Poole, who chaired the conference, with Hewlyn Heywood. Assistant Director of Nursing Services, Moorfields Eye Hospital. PMID- 27652749 TI - Nurse specialists could lead to fragmentation. AB - The increasing number of clinical nurse specialists could result in a return to task orientation and fragmentation of care, it was claimed. Sophie Thomas, a senior nurse from the Hammersmith Hospital Haematology Unit, described this as one of the threats posed to nursing by an increasingly specialised, high technology health service. PMID- 27652748 TI - ? AB - Helen Ference, Director of the American-based Nightingale Society, holds an unpublished letter written by Florence Nightingale. The Nightingale Society was just one of the exhibitors at the 'Excellence in contemporary clinical nursing' conference. PMID- 27652752 TI - World news. AB - United States The American Nurses Association has moved to safeguard the rights of patients to demand protection against HIV transmission in hospitals and clinics. PMID- 27652750 TI - Reality orientation can be 'distressing and cruel'. AB - Reality orientation (RO) can be very distressing for many elderly, severely demented patients, the conference was told. PMID- 27652753 TI - Cure for Alzheimer's disease 'in 50 years'. AB - A genetic cure for Alzheimer's disease and improved drug treatments will be within reach in 50 years time, a nurse specialist from the Department of Genetics at Nottingham's City Hospital told a conference organised by the Community Psychiatric Nursing Association. PMID- 27652755 TI - ? AB - A presentation flip-chart designed to help practice nurses in counselling clients on the risks associated with heart disease, endorsed by the RCN, has been produced by the The Flora Project for Heart Disease Prevention. Practice nurses can get a free copy of the Primary Care Presenter from: Flora Project for Heart Disease Prevention, PO Box 1392, Sudbury, Suffolk CO10 6FS. PMID- 27652754 TI - Milk extract used to reduce tooth decay. AB - Tests on a compound extracted from milk show it reduces the incidence of dental cavities and helps repair tooth decay. PMID- 27652756 TI - Folic acid 'prevents neural tube defects'. AB - Folic acid supplements prevent neural tube defects and should be given to women who have previously had an affected pregnancy, the Medical Research Council's vitamin study shows. The Council has called for a public health campaign to ensure the diet of all women of child-bearing age contains an adequate amount of the B-group vitamin. PMID- 27652758 TI - Stroke prevention in people over sixty. AB - In people aged 60 or more with isolated systolic hypertension, treatment can reduce the incidence of stroke and major cardiovascular events. PMID- 27652757 TI - Study links diabetes risk to deprivation. AB - Studies attempting to show a link between the incidence of diabetes and social class have so far proved inconclusive but researchers from the north of England have established that the incidence of childhood diabetes is related to material deprivation. PMID- 27652759 TI - Volume size and pain of insulin injection. AB - The pain of insulin injection is associated with the bluntness of the needle rather than the volume injected. PMID- 27652761 TI - Evidence for vertical spread of hepatitis C. AB - It is possible for hepatitis C virus (HCV) to be transmitted vertically, researchers from California claim. PMID- 27652760 TI - Insulin misuse in diabetic women. AB - Clinical eating disorders are no more common in diabetic women than in non diabetics but disturbed eating is associated with insulin misuses to influence body weight. PMID- 27652763 TI - Learning bullseye. AB - Peter Newberry reckons that since he qualified six years ago, a grand total of L60 has been invested in his postregistration education by various health authorities. He is probably typical of many nurses; he could, in fact, be one of the lucky ones. PMID- 27652762 TI - Ribavarin efficacy in HIV disease. AB - Ribavarin might be a useful drug, used in combination, to prevent progression of HIV disease, researchers say. PMID- 27652764 TI - College of steel. AB - Did you hear about the Swazi chief, the Catalunian Giant and the Sheffield 'buffer girl? Probably not unless you are a Project 2000 student from the Sheffield and North Trent College of Nursing and Midwifery. PMID- 27652765 TI - Coming up roses. AB - Nearly 40 years ago a group of entrepreneurial nurses formed a small network of home-based nursing agencies which has grown to become the largest in the United Kingdom. The British Nursing Association is now arguably the best- known nursing agency in the country and its parent company is spreading its wings in the international scene. PMID- 27652766 TI - The dilemma of 'them' and 'us'. AB - It would seem that Pamela Chari wood, Director of the Institute of Health Service Management, cannot or will not believe the evidence before her (Letters, Nursing Standard July 17). If she'd read all the articles by Catherine Williams et al in Nursing Standard on why nurses leave the profession, she would have seen that it is indeed a question of 'them' and 'us', and very much so. PMID- 27652768 TI - Information exchange. AB - As part of an ongoing assessment of the effectiveness of practice, we are researching the function/usefulness of community meetings in an acute psychiatric admission ward setting. We are currently searching for information from other wards and units. Does anyone have any information sheets for staff or clients or any other information/ references they could share with us? PMID- 27652767 TI - 'Ear waxing lyrical'. AB - In response to Rosemary Cook's article 'Ear waxing lyrical' (Nursing Standard July 3), there is a lot more to ears than just syringing and there are a lot more joys to find than helping one elderly person. My survey among the elderly population of the area I work in showed that between 64-80 per cent of elderly people examined had some kind of ear problem. PMID- 27652769 TI - Commenting on hepatitis. AB - The interesting article by Marie Kedzierski on 'Management of viral hepatitis' (Nursing Standard July 10) referred to several practices in relation to hepatitis A infection which are not always required in modern hospitals. PMID- 27652770 TI - Nurse's Pocket Guide: Nursing Diagnoses with Interventions M Doenges M Moorbouse Nurse's Pocket Guide: Nursing Diagnoses with Interventions F A Davis 548pp L12.00 0-8036-2666-5 [Formula: see text]. AB - My first thought when I began to read the Nurse's Pocket Guide: Nursing Diagnoses with Interventions was 'at last, a nursing dictionary instead of the usual medical dictionary for nurses!' Unfortunately, it did not live up to my expectations. The book starts out with a good idea but, like so many others, fails to communicate it effectively and simply. PMID- 27652771 TI - Pain Control, 2nd edition J Latham Pain COntrol, 2nd edition Austen Cornish 122pp L6.50 1-870065-16-6. AB - Pain Control introduces the complex and multifaceted problem of pain control with which nurses are daily confronted. The opening chapters relate to the appropriate anatomy, physiology and development of pain theories. The explanation of the Gate Control Theory, in particular, is easily read and informative. PMID- 27652772 TI - Case Studies in Critical Care Nursing B Mims Case Studies in Critical Care Nursing Williams & Wilkins 556pp L26.00 0-683-06051-7 [Formula: see text]. AB - Case Studies in Critical Care Nursing is an exciting book for the critical care nurse who is striving to develop skills in analysing the complex needs of the critically ill patient. It will enable nurses to play a vital role in co ordinating and focusing the efforts of the many health care workers toward realistic patient-orientated goals. PMID- 27652773 TI - Feeling the pinch. PMID- 27652774 TI - Listings. PMID- 27652775 TI - A new frontier in CO2 flux measurements using a highly portable DIAL laser system. AB - Volcanic CO2 emissions play a key role in the geological carbon cycle, and monitoring of volcanic CO2 fluxes helps to forecast eruptions. The quantification of CO2 fluxes is challenging due to rapid dilution of magmatic CO2 in CO2-rich ambient air and the diffuse nature of many emissions, leading to large uncertainties in the global magmatic CO2 flux inventory. Here, we report measurements using a new DIAL laser remote sensing system for volcanic CO2 (CO2DIAL). Two sites in the volcanic zone of Campi Flegrei (Italy) were scanned, yielding CO2 path-amount profiles used to compute fluxes. Our results reveal a relatively high CO2 flux from Campi Flegrei, consistent with an increasing trend. Unlike previous methods, the CO2DIAL is able to measure integrated CO2 path amounts at distances up to 2000 m using virtually any solid surface as a reflector, whilst also being highly portable. This opens a new frontier in quantification of geological and anthropogenic CO2 fluxes. PMID- 27652776 TI - Introduction to Purinergic Regulation in the Eye Special Issue. PMID- 27652777 TI - Structure and catalytic mechanism of monodehydroascorbate reductase, MDHAR, from Oryza sativa L. japonica. AB - Ascorbic acid (AsA) maintains redox homeostasis by scavenging reactive oxygen species from prokaryotes to eukaryotes, especially plants. The enzyme monodehydroascorbate reductase (MDHAR) regenerates AsA by catalysing the reduction of monodehydroascorbate, using NADH or NADPH as an electron donor. The detailed recycling mechanism of MDHAR remains unclear due to lack of structural information. Here, we present the crystal structures of MDHAR in the presence of cofactors, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), and complexed with AsA as well as its analogue, isoascorbic acid (ISD). The overall structure of MDHAR is similar to other iron sulphur protein reductases, except for a unique long loop of 63-80 residues, which seems to be essential in forming the active site pocket. From the structural analysis and structure-guided point mutations, we found that the Arg320 residue plays a major substrate binding role, and the Tyr349 residue mediates electron transfer from NAD(P)H to bound substrate via FAD. The enzymatic activity of MDHAR favours NADH as an electron donor over NADPH. Our results show, for the first time, structural insights into this preference. The MDHAR-ISD complex structure revealed an alternative binding conformation of ISD, compared with the MDHAR-AsA complex. This implies a broad substrate (antioxidant) specificity and resulting greater protective ability of MDHAR. PMID- 27652778 TI - Lysosomal storage disorders. PMID- 27652779 TI - Myriad maladies. PMID- 27652780 TI - Biomedicine: A rare opportunity. PMID- 27652781 TI - Perspective: The rare must become common. PMID- 27652782 TI - Advocacy: Strong foundations. PMID- 27652783 TI - Drug development: Through the barrier. PMID- 27652784 TI - Gene therapy: A new chapter. PMID- 27652785 TI - Perspective: Finding common ground. PMID- 27652786 TI - Screening: Baby's first test. PMID- 27652787 TI - Lysosomal storage disorders: 4 big questions. PMID- 27652788 TI - Theory of tailorable optical response of two-dimensional arrays of plasmonic nanoparticles at dielectric interfaces. AB - Two-dimensional arrays of plasmonic nanoparticles at interfaces are promising candidates for novel optical metamaterials. Such systems materialise from 'top down' patterning or 'bottom-up' self-assembly of nanoparticles at liquid/liquid or liquid/solid interfaces. Here, we present a comprehensive analysis of an extended effective quasi-static four-layer-stack model for the description of plasmon-resonance-enhanced optical responses of such systems. We investigate in detail the effects of the size of nanoparticles, average interparticle separation, dielectric constants of the media constituting the interface, and the nanoparticle position relative to the interface. Interesting interplays of these different factors are explored first for normally incident light. For off-normal incidence, the strong effects of the polarisation of light are found at large incident angles, which allows to dynamically tune the reflectance spectra. All the predictions of the theory are tested against full-wave simulations, proving this simplistic model to be adequate within the quasi-static limit. The model takes seconds to calculate the system's optical response and makes it easy to unravel the effect of each system parameter. This helps rapid rationalization of experimental data and understanding of the optical signals from these novel 'metamaterials', optimised for light reflection or harvesting. PMID- 27652789 TI - Laparoscopic repair of congenital duodenal obstruction is feasible even in small volume centres. AB - INTRODUCTION It has been suggested that laparoscopic repair of congenital duodenal obstruction (CDO) should be restricted to a limited number of designated centres of expertise. After gaining extensive experience with intracorporeal suturing in other procedures, we evaluated the feasibility of this approach at the Royal Hospital for Sick Children (RHFSC; Edinburgh, UK). METHODS We conducted a retrospective review of all cases of CDO presenting to the RHFSC from 2012 to 2014. Cases were identified from our electronic database using standardised codes. Data comprised: gestation; birth weight; associated anomalies; patient age and weight at surgery; operative time; complications; postoperative course. RESULTS Five consecutive non-selected cases of isolated CDO were repaired laparoscopically, and all were carried out by the senior surgeon. The male:female ratio was 4:1. Corrected gestational age at surgery was 35-38 weeks, and the weight at surgery was 1.7-3.1 kg. None of our patients had significant associated anomalies. CONCLUSIONS The present study demonstrates the feasibility of laparoscopic repair of CDO in small-volume centres, and is the first report of laparoscopically managed congenital duodenal atresia in twins. PMID- 27652791 TI - Virtual fracture clinic delivers British Orthopaedic Association compliance. AB - INTRODUCTION The British Orthopaedic Association recommends that patients referred to fracture clinic are thereafter reviewed within 72 hours. With the aim of improving care by seeking to meet this target, waiting times for fracture clinic appointments in a district general hospital were audited prospectively against this national guideline, with the intervening implementation of a virtual fracture clinic. MATERIALS AND METHODS The study was conducted as a prospective closed-loop audit in which the second cycle took place several months after a change in the clinical pathway for all referrals from the emergency department to fracture clinic. Data were gathered in real-time via a pro forma during fracture clinic consultations. RESULTS The first cycle demonstrated a non-compliant mean waiting time of 10.7 days, with 6% of patients being seen within the 72-hour target. Following the implementation of the virtual fracture clinic, the second cycle found that all patients were reviewed within the 72-hour target (mean 1.3 days). DISCUSSION The improvement in performance was delivered with no increase in clinic capacity. The cost of implementation was negligible. CONCLUSION A simple virtual fracture clinic model delivered a significant reduction in waiting times and achieved compliance with the British Orthopaedic Association guideline. Similar results could be achieved in subsequent deployment elsewhere in the NHS. PMID- 27652790 TI - Comparison of magnetic resonance arthrography with arthroscopy for imaging of shoulder injuries: retrospective study. AB - BACKGROUND Arthroscopy is the established 'gold standard' diagnostic investigation for detection of shoulder disorders. We aimed to compare the diagnostic accuracy of arthroscopy with magnetic resonance arthrography (MRA) for detection of shoulder disorders. METHODS Patients who underwent arthroscopy by a single surgeon and preoperative MRA between February 2011 and March 2012 for shoulder instability were identified. MRAs were reported by experienced musculoskeletal radiologists. Labral tears, anterior labral tears, superior labral anterior posterior (SLAP) lesions, posterior labral tears, rotator-cuff tears (RCTs), osteoarthritis, loose bodies and Hill-Sachs lesions were identified. Sensitivity, specificity, positive predictive value and negative predictive value, positive likelihood ratio and negative likelihood ratio were calculated. RESULTS A total of 194 patients were identified. The sensitivity and specificity for anterior labral tears was 0.60 and 0.92, SLAP lesions was 0.75 and 0.81, posterior labral tears was 0.57 and 0.96, any labral tear was 0.87 and 0.76, Hill-Sachs lesions was 0.91 and 0.91, RCTs was 0.71 and 0.86, osteoarthritis was 0.72 and 0.95, and loose bodies was 0.22 and 0.96, respectively. The positive predictive value and negative predictive value for anterior labral tears were 0.88 and 0.71, SLAP lesions was 0.64 and 0.88, posterior labral tears was 0.74 and 0.45, any labral tear was 0.89 and 0.71, Hill Sachs lesions was 0.66 and 0.98, RCTs was 0.47 and 0.95, osteoarthritis was 0.70 and 0.95, and loose bodies was 0.27 and 0.95, respectively. CONCLUSIONS MRA has high diagnostic accuracy for labral tears and Hill-Sachs lesions, but whether MRA should be the first-line imaging modality is controversial. PMID- 27652792 TI - Specimen 'sandwich' - orientating the operative specimen in breast surgery. PMID- 27652793 TI - Transition from paediatric surgery: how many patients do we need to plan for? AB - INTRODUCTION Transitional care is an NHS priority with newly published NICE guidance. Many paediatric surgical patients need quality care to continue into adulthood. We undertook an evaluation of our departmental activity to assess the magnitude of this issue. METHODS We identified all outpatients >= 15 years (potentially requiring imminent transition) seen over a 12 month period for all five general paediatric surgery consultants in our tertiary centre. Those patients requiring transition were highlighted and the appropriate adult team for referral recorded. RESULTS There were 2989 general paediatric surgery clinic appointments within the year; 289 (9.7%) were for young people aged 15 years or older; 62 patients (28% of those >= 15years) were deemed to require transition into adult care. Significantly more patients having colorectal surgery required follow-up (P = 0.0009 Chi-square test) compared with patients in other subspecialties. CONCLUSIONS More patients than expected required transition. This may be the case in other units. Current best practice includes time intensive preclinic planning, careful preparation of patient and family, followed by joint clinics. A joint clinic appointment takes 30 minutes, allowing for comprehensive handover and forging new relationships. In our department, we need at least ten transition clinics across 2 years. Coalition with adult colleagues is vital. These data enable us to plan services to provide quality care for our adolescent patients and highlights colorectal surgery as a priority. PMID- 27652794 TI - Choosing between the modified Ravitch and Nuss procedures for pectus excavatum: Considering the patients's perspective. AB - INTRODUCTION Pectus excavatum (PE) is the most common paediatric chest wall deformity. The majority of patients are treated for cosmetic purposes, with the modified Ravitch and Nuss procedures the most commonly performed. We tested the preferences of healthy individuals over their choice of procedure. METHODS The study was conducted from February to August 2014. A five-item illustrated questionnaire was administered to teenagers and young adults aged 14-26 years over their willingness to seek medical advice if they had PE, provided its cosmetic appearance was the only complaint. They were asked about their preference over the modified Ravitch and Nuss procedures, with the surgical details for both procedures explained by medical professionals, alongside illustrated outcomes. RESULTS Two hundred and two healthy individuals were interviewed. The median age was 19.5 years (14-26 years) and 141 (69.8%) were male. Sixty seven (33.2%) participants refused any intervention, while 11 (5.4%) initially wanted an intervention but refused after understanding the surgical procedures available. Of the 135 respondents who chose surgical correction, 84 (62.2%) preferred the modified Ravitch operation, while 51 (37.8%) preferred the Nuss procedure. The main reason for choosing the modified Ravitch technique was not having something metal in the chest, while most participants who chose the Nuss procedure felt that it was "cosmetically better". CONCLUSIONS Patients have preferences over the choice of procedure for PE repair that can affect the treatment decision. Paediatric and thoracic surgeons should therefore be experienced in performing both procedures. PMID- 27652795 TI - Portal vein thrombosis following laparoscopic gastric plication. AB - Portal vein thrombosis (PVT) following laparoscopic surgery including Roux-en-Y bypass, sleeve gastrectomy and Nissen's fundoplication is a rare but recognised complication. Laparoscopic gastric plication in a new procedure that is popular in some parts of the world. We report a case of a patient suffering PVT as a complication of this surgery. PMID- 27652796 TI - An atypical case of medial radial head dislocation. AB - Radial head dislocations are common in children who fall onto outstretched hands. We present a case of medial radial head dislocation without a concomitant ulna fracture in a 14-year-old girl and the long-term sequelae of the injury. PMID- 27652797 TI - Tension pneumoperitoneum: a very rare complication of acute gangrenous appendicitis. AB - Tension pneumoperitoneum is a very rare consequence of acute gangrenous appendicitis. We report a case of a 32-year-old woman who presented with abdominal pain, progressively increasing abdominal distension, profound hemodynamic instability and ventilatory compromise. The diagnosis of tension pneumoperitoneum was confirmed by computed tomography, which showed compression of the intra-abdominal viscera and liver (saddlebag sign) by a large volume of intraperitoneal free air. Urgent needle decompression was done as an emergency measure. Exploratory laparotomy, planned due to persistent peritonitis, revealed gangrenous appendicitis with perforation near its base. Appendicectomy with excision of gangrenous portion of caecum was performed. The purpose of the reporting this case is to highlight that the tension pneumoperitoneum can be, very rarely, associated with gangrenous appendicitis and timely diagnosis is very important for the emergency management of this deadly condition. PMID- 27652798 TI - Transanal total mesorectal excision: technical aspects of approaching the mesorectal plane from below. AB - Standardization of transanal total mesorectal excision requires the delineation of the principal procedural components before implementation in practice. This technique is a bottom-up approach to a proctectomy with the goal of a complete mesorectal excision for optimal outcomes of oncologic treatment. A detailed stepwise description of the approach with technical pearls is provided to optimize one's understanding of this technique and contribute to reducing the inherent risk of beginning a new procedure. Surgeons should be trained according to standardized pathways including online preparation, observational or hands-on courses as well as the potential for proctorship of early cases experiences. Furthermore, technological pearls with access to the "video-in-photo" (VIP) function, allow surgeons to link some of the images in this article to operative demonstrations of certain aspects of this technique. PMID- 27652800 TI - Factors influencing insulin usage among type 2 diabetes mellitus patients: A study in Turkish primary care. AB - BACKGROUND: DM (diabetes mellitus) patients with poorly regulated blood glucose levels are at risk of increased morbidity and mortality. There are different factors that cause resistance to the initiation of insulin therapy such as beliefs and perceptions concerning diabetes and its treatment and the nature and consequences of insulin therapy. OBJECTIVES: We aimed to explore the reasons for this reluctance and how these obstacles could be overcome so that DM patients who require insulin could initiate therapy. METHODS: This was a cross-sectional, descriptive study of diabetic patients with glycated haemoglobin A1c (HbA1C) levels above 7.0%, who were followed-up at a primary care and endocrinology outpatient clinic. RESULTS: Ninety-four patients (57.4% females, 42.6% males) were recruited for this study. Most patients (57.4%) considered that insulin was a drug of last resort. Among all patients, 34.1% thought that insulin lowered blood glucose levels to an extreme degree and 14.9% disagreed. The patients thought that self-injection was hard (27.6%), required someone else to administer the injection (27.6%), insulin injection was painful (33.0%). 59.6% of all patients believed that their religion did not restrict the use of insulin, 52.1% stated that their family physicians had sufficiently informed them. CONCLUSION: Our most significant finding is that a lack of adequate information relating to insulin appears to be the major factor behind DM patients' refusal of insulin treatment. The fact that patients consider insulin treatment as a final solution to DM could be related to resistance to the initiation of insulin therapy. [Box: see text]. PMID- 27652799 TI - What's a SNP between friends: The influence of single nucleotide polymorphisms on virulence and phenotypes of Clostridium difficile strain 630 and derivatives. AB - Clostridium difficile is a major cause of antibiotic induced diarrhea worldwide, responsible for significant annual mortalities and represents a considerable economic burden on healthcare systems. The two main C. difficile virulence factors are toxins A and B. Isogenic toxin B mutants of 2 independently isolated erythromycin-sensitive derivatives (630E and 630Deltaerm) of strain 630 were previously shown to exhibit substantively different phenotypes. Compared to 630, strain 630E and its progeny grow slower, achieve lower final cell densities, exhibit a reduced capacity for spore-formation, produce lower levels of toxin and are less virulent in the hamster infection model. By the same measures, strain 630Deltaerm and its derivatives more closely mirror the behavior of 630. Genome sequencing revealed that 630Deltaerm had acquired 7 unique Single Nucleotide Polymorphisms (SNPs) compared to 630 and 630E, while 630E had 9 SNPs and a DNA inversion not found in the other 2 strains. The relatively large number of mutations meant that the identification of those responsible for the altered properties of 630E was not possible, despite the restoration of 3 mutations to wildtype by allelic exchange and comparative RNAseq analysis of all 3 strains. The latter analysis revealed large differences in gene expression between the 3 strains, explaining in part why no single SNP could restore the phenotypic differences. Our findings suggest that strain 630Deltaerm should be favored over 630E as a surrogate for 630 in genetic-based studies. They also underline the importance of effective strain curation and the need to genome re-sequence master seed banks wherever possible. PMID- 27652801 TI - Histologic and metabolic assessment in a cohort of patients with genital prolapse: preoperative stage and recurrence investigations. AB - BACKGROUND: Biological basis of prolapse development and recurrence are still unclear. Aim of this observational and prospective study is to correlate clinical stage of anterior vaginal wall prolapse and anatomical recurrence to histological and metabolic characteristics of vaginal tissue. METHODS: Patients undergoing surgery were divided into two groups according to anterior stage <=II (group A) and >=III (group B). Full-thickness excisional biopsies of the anterior vaginal wall were obtained after hysterectomy. Hystological characteristics and metalloproteinases activity (MMP-2) were analyzed. RESULTS: Sixty-nine patients (35 group A; 34 group B) completed evaluation. Mean follow-up was 35 months. Collagen amount and organization were significantly higher in group B both in lamina propria and fascia specimens, but MMP-2 activity was significantly lower in this group. Recurrence rate of anterior compartment was 10.1%. Collagen cellularity of fascia was higher in recurrence groups. On the contrary MMP-2 activity showed a close to significant correlation to surgical success (P=0.07). CONCLUSIONS: Patients with advanced stages of prolapse have increased collagen amount associated to decreased MMP-2 activity. This suggests that connective tissue is more abundant but less metabolically active in patients with severe prolapse. A similar trend can be found in recurrences. PMID- 27652802 TI - Distance between Great Vessels and the Lumbar Spine: MRI Study for Anterior Longitudinal Ligament Release Through a Lateral Approach. AB - Objective Anterior column reconstruction using the lateral transpsoas approach requires sectioning of the anterior longitudinal ligament while protecting the great vessels. Our aim was to study the anatomical plane of separation between the retroperitoneal vessels and the anterior aspect of the lumbar spine as they relate to safety in the lateral transpsoas anterior column reconstruction procedure. Method A total of 100 T2-weighted magnetic resonance imaging (MRI) examinations were studied. Measurements were obtained for each vertebral body and for each intervertebral disk levels from L1-L2 to L4-L5, and for these vessels: abdominal aorta, inferior vena cava , and common iliac vessels. The following parameters were obtained: (sagittal) total lumbar lordosis and segmental lordosis; (axial) closest distance (areolar space [AS]) between the lumbar spine and vessels; and position of the great vessels. Results The AS was differently distributed for the abdominal aorta and the inferior vena cava. Average values for the inferior vena cava were larger at upper levels (p < 0.001; range: 0.2-9.2 mm), and there were differences between the arteries among the levels (p < 0.001; range: 1.0-4.3 mm) but with no clear difference between the upper and lower lumbar spine. A narrower AS was found at the intervertebral disk level compared with the adjacent vertebral body. At L4-L5, the veins usually lay over the anterior border of the lumbar spine, with substantially wider AS at other lumbar levels. Conclusion The plane between the great vessels and the lumbar spine is differently distributed along the lumbar spine and is especially narrow at lower lumbar levels and in front of the intervertebral disk. The results shown here may help guide surgical decision making for the lateral anterior column reconstruction and may aggregate data from dislocation of the vessels in the lateral decubitus and individualized analysis. PMID- 27652803 TI - Minimally Invasive Direct Lateral Corpectomy of the Thoracolumbar Spine for Metastatic Spinal Cord Compression. AB - Objectives To evaluate the feasibility, safety, clinical, and radiologic outcomes of a minimally invasive direct lateral-approach corpectomy (MIDLaC) for decompression and stabilization of symptomatic metastatic spinal cord compression (MSCC). Methods A retrospective study on a prospective cohort was conducted. Nineteen patients were consecutively treated with MIDLaC and posterior pedicle screw fixation between May 2012 and July 2014. Demographic information and radiologic outcomes including sagittal deformity correction and vertebral body height were recorded. Operative variables (operative duration, blood loss) and clinical variables (Tokuhashi score, mortality, complication rate, pain visual analogue scale [VAS], opioid usage, and Frankel grade) were recorded and analyzed. Results All nineteen patients (mean age: 67.6 +/- 12.7 years) successfully underwent MIDLaC with excellent neural decompression. Operative duration was 188.4 +/- 30.3 minutes for single-level MIDLaC and 327.2 +/- 71.9 minutes for multilevel surgery (p < 0.0001). Mean blood loss per spinal level was 390.8 mL with a decrease to 102.3 mL excluding renal cell MSCC. A total of 47.4% of patients had a Tokuhashi score of 0 to 8. There was one approach-related complication and one perioperative mortality. The overall complication rate was 15.8% (n = 3) with no postoperative wound infections. Kaplan-Meier survival estimates at 6 months were 0.50. Overall, 31.6% of patients improved by one or more Frankel grades, and no patients demonstrated worsening neurology postoperatively. VAS was significantly improved postoperatively (p < 0.05). Vertebral body height was significantly increased (+7.6 +/- 8.1 mm; p = 0.002), with improvements in lumbar lordosis (8.3 +/- 7.3 degrees) and thoracic kyphosis (2.4 +/- 7.1 degrees) postoperatively. Conclusion MIDLaC is a safe and feasible palliative approach in the management of MSCC with encouraging early clinical outcomes. Further prospective studies are required to define the role of MIDLaC in the management of MSCC vis-a-vis other mini-open or minimally invasive techniques. PMID- 27652804 TI - Biportal Endoscopic Lumbar Decompression for Lumbar Disk Herniation and Spinal Canal Stenosis: A Technical Note. AB - Background and Study Aims Endoscopic lumbar diskectomy through the interlaminar window is gaining recognition. Most of the literature describes these endoscopic procedures using specialized uniportal multichannel endoscopes. However, a single portal limits the motion of the instruments and obscures visualization of the operating field. To overcome this limitation, we propose a new technique that utilizes two portals to access the spinal canal. The biportal endoscopic lumbar decompression (BELD) technique uses two portals to treat difficult lumbar disk herniations and also lumbar spinal stenoses. Patients and Methods Seventeen patients were treated with BELD for 11 lumbar disk herniations and 6 lumbar spinal stenoses. Preoperative back and leg visual analog scale (VAS-B and VAS-L, respectively) scores and the Oswestry Disability Index (ODI) were recorded and compared with corresponding values on final follow-up. Results There was an average follow-up of 14 months. For the disk herniation group, preoperative VAS-L (7.8750 +/- 1.24) and ODI (51.73 +/- 18.57) was significantly different from follow-up postoperative VAS-L (0.87 +/- 0.64, p = 0.000) and ODI (9.37 +/- 4.83, p = 0.001). For the stenosis group, preoperative VAS-B (6.17 +/- 1.94), VAS L(7.83 +/- 1.47), and ODI (63.27 +/- 7.67) were significantly different from follow-up postoperative values (2.5 +/- 1.04, p = 0.022; 2.00 +/- 1.67, p = 0.001; 24.00 +/- 6.45, p = 0.000, respectively). One patient underwent revision microdiskectomy for incomplete decompression. Conclusions BELD can achieve a similar decompression effect as microdiskectomy and unilateral laminotomy for bilateral decompression with a smaller incision than tubular diskectomy. PMID- 27652805 TI - A favorable outcome from dengue hemorrhagic fever: Teaching Hospital Kandy, Sri Lanka, May 2016. PMID- 27652806 TI - A Novel Platelet-Repellent Polyphenolic Surface and Its Micropattern for Platelet Adhesion Detection. AB - Surface patterning provides a powerful tool to the diagnosis of platelet adhesion. However, the current methodologies of constructing platelet-patterned surfaces require laborious and complicated steps. Herein, a novel and simple platelet-repellent surface was reported by metal (Fe3+ ions)-polyphenol (tannic acid, TA) coordination interaction. The platelet-repellent effect was significantly better than that of poly(ethylene glycol) (PEG) in a long-term. Moreover, the platelet-repellent behavior could extend to other polyphenols functionalized surfaces. On the basis of these observations, a TA-based micropattern was fabricated in situ by one-step microcontact printing for well defined platelet adhesion, which can effectively avoid the traditional introduction of inert hydrophilic polymers and bioactive ligands. Afterward, the TA-based micropattern was applied to monitor the adhesion of defective platelets treated with an antiplatelet drug (tirofiban). This work provided a facile, versatile, and environmentally friendly strategy to construct platelet-repellent polyphenolic surfaces and their micropattern. We expect that this simple micropattern could act as a low-cost and label-free platform for biomaterials and biosensors, and could be widely used in the clinical diagnoses of platelet adhesive functions and the evaluation of antiplatelet therapies. PMID- 27652807 TI - Photoinduced Electron Transfer and Hole Migration in Nanosized Helical Aromatic Oligoamide Foldamers. AB - A series of photoactive triads have been synthesized and investigated in order to elucidate photoinduced electron transfer and hole migration mechanism across nanosized, rigid helical foldamers. The triads are comprised of a central helical oligoamide foldamer bridge with 9, 14, 18, 19, or 34 8-amino-2 quinolinecarboxylic acid repeat units, and of two chromophores, an N-terminal oligo(para-phenylenevinylene) electron donor and a C-terminal perylene bis-imide electron acceptor. Time-resolved fluorescence and transient absorption spectroscopic studies showed that, following photoexcitation of the electron acceptor, fast electron transfer occurs initially from the oligoquinoline bridge to the acceptor chromophore on the picosecond time scale. The oligo(para phenylenevinylene) electron donor is oxidized after a time delay during which the hole migrates across the foldamer from the acceptor to the donor. The charge separated state that is finally generated was found to be remarkably long-lived (>80 MUs). While the initial charge injection rate is largely invariant for all foldamer lengths (ca. 60 ps), the subsequent hole transfer to the donor varies from 1 * 109 s-1 for the longest sequence to 17 * 109 s-1 for the shortest. In all cases, charge transfer is very fast considering the foldamer length. Detailed analysis of the process in different media and at varying temperatures is consistent with a hopping mechanism of hole transport through the foldamer helix, with individual hops occurring on the subpicosecond time scale (kET = 2.5 * 1012 s-1 in CH2Cl2). This work demonstrates the possibility of fast long-range hole transfer over 300 A (through bonds) across a synthetic modular bridge, an achievement that had been previously observed principally with DNA structures. PMID- 27652808 TI - How long should dual antiplatelet therapy be used in diabetic patients after implantation of drug-eluting stents? AB - PURPOSE OF REVIEW: To analyze evidence from randomized clinical trials (RCTs) that identifies the optimal duration of dual antiplatelet therapy (DAPT) after implantation of newer generation drug-eluting stents (DESs) in diabetic patients. RECENT FINDINGS: Patients with diabetes mellitus have increased risk of ischemic events and bleeding after DES implantation. The optimal duration of DAPT for this population is currently unknown. In a subgroup analysis of 8542 diabetic patients enrolled in eight RCTs of DAPT duration after implantation of newer generation DESs, prolonged courses of DAPT of 12-36 months in duration resulted in rates of major adverse cardiac events that were no different from those seen after shorter courses of DAPT of 3-12 months in duration (odds ratio 1.00, 95% Bayesian credible interval 0.74-1.33). SUMMARY: Prolonged DAPT up to 36 months after newer generation DES implantation in diabetic subgroups has not been associated with better outcomes than shorter courses of 3-12 months. Until dedicated trials are completed in diabetic populations, DAPT duration after newer generation DES implantation in patients with diabetes mellitus should follow recommendations for the general population. PMID- 27652809 TI - Aortic disease and pregnancy. AB - PURPOSE OF REVIEW: During pregnancy, cardiac disease is the most important cause of maternal mortality, with aortic disease being the most important contributor. This review describes the impact of pregnancy, risk stratification for and the management of aortic diseases during pregnancy and delivery. RECENT FINDINGS: The most common aortic diseases with an increased risk of complications during pregnancy are genetic syndromes such as Marfan, Loeys-Dietz, vascular Ehlers Danlos, Turner syndrome and bicuspid aortic valve. The key management of aortic dilatation consists of prepregnancy counseling, including imaging of the entire aorta and preventive treatment when indicated. The possible treatment options for aortic dissection during pregnancy are medication and surgical treatment. Percutaneous interventions are associated with a high risk. SUMMARY: The heterogeneity of aortic diseases underlines the need for an individual risk assessment and management. A dedicated plan for diagnosis, management, follow-up, labor and delivery should be formulated by an experienced multidisciplinary team. PMID- 27652810 TI - Primary tumors of the heart. AB - PURPOSE OF REVIEW: Primary cardiac tumors are a rare disease, which may have severe clinical consequences. Malignant tumors may be misdiagnosed as mixomas, with improper treatment. The aim of this review is to report how to make a differential diagnosis using old and modern tools, the latest trends in tumor classification and treatment, and their possible impact on prognosis. RECENT FINDINGS: Papillary fibroelastomas seem to be more frequent than previously reported, and surgery is also suggested in asymptomatic patients. A genetic background has been identified for some myxomas and angiosarcomas. Malignant tumors are now classified as soft-tissue sarcomas of other organs. Immunohistochemistry and molecular diagnosis aid in recognizing several subtypes of sarcomas, leading to the possibility of targeted chemotherapy. The reports of single-center and multicenter experiences, collecting a large number of treated patients, analyzed the impact on prognosis of different approaches. The best results for survival and event-free survival are obtained with the multimodality approach. SUMMARY: Before referring a patient with cardiac tumor to the cardiac surgeon, a presumptive diagnosis of benignity or malignancy should be obtained. Malignant tumors should be referred to a cardiac tumor team with special expertise, in order to plan the best therapeutic approach. PMID- 27652812 TI - Cardiovascular consequences of obstructive sleep apnea. AB - PURPOSE OF REVIEW: There is an increased awareness of obstructive sleep apnea (OSA) and its potential impact on cardiovascular diseases (CVDs). The number of patients diagnosed with OSA is likely to increase as the obesity epidemic continues to grow. We review recent publications that have examined the links between OSA and CVD. RECENT FINDINGS: The cardiovascular consequences of OSA include hypertension, strokes, atrial fibrillation, and heart failure. It is likely that these are related to OSA-induced changes in endothelial dysfunction, oxidative stress, and systemic inflammation. The mainstay of treatment of OSA remains positive airway pressure devices (PAP), but issues of adherence continue to plague effective management. Oral appliances may also be a suitable alternative and may have a similar effect on blood pressure as PAP. To date, randomized trials have verified a significant (though relatively modest) impact of PAP on blood pressure, and some have shown an improvement in glucose control in diabetic individuals. However, it is unclear whether PAP prevents cardiovascular events in patients with OSA, although patients well managed and adherent with PAP seem to do better than those who are nonadherent. SUMMARY: The mortality and morbidity associated with OSA are reduced in patients well managed with PAP. However, we await the results of large randomized clinical trials to definitely determine whether PAP reduces the rate of cardiovascular events. Current efforts aimed at identifying biomarkers in OSA may offer a strategy for personalized treatment plans of OSA patients. PMID- 27652811 TI - Microvascular dysfunction in patients with diabetes after cardioplegic arrest and cardiopulmonary bypass. AB - PURPOSE OF REVIEW: The purpose of the current review is to describe the changes of microvascular function in patients with diabetes after cardioplegic arrest and cardiopulmonary bypass (CPB) and cardiac surgery. RECENT FINDINGS: Cardiac surgery, especially that involving cardioplegia and CPB, is associated with significant changes in vascular reactivity of coronary/peripheral microcirculation, vascular permeability, gene/protein expression, and programmed cell death, as well as with increased morbidity and mortality after surgical procedures. In particular, these changes are more profound in patients with poorly controlled diabetes. SUMMARY: Because alterations in vasomotor regulation are critical aspects of mortality and morbidity of cardioplegia/CPB, a better understanding of diabetic regulation of microvascular function may lead to improved postoperative outcomes of patients with diabetes after cardioplegia/CPB and cardiac surgery. PMID- 27652813 TI - The value of noninvasive computed tomography derived fractional flow reserve in our current approach to the evaluation of coronary artery stenosis. AB - PURPOSE OF REVIEW: Contemporary diagnosis and management of stable chest pain symptoms possibly due to coronary ischemia is a frequent clinical challenge that involves a variety of test options, based upon either coronary angiographic (anatomic) or functional imaging. This review will discuss the evolution of coronary computed tomography derived fractional flow reserve (FFRCT) from basic science to a currently clinically approved diagnostic test. RECENT FINDINGS: In recent years, FFR measured invasively in the coronary catheterization lab has demonstrated clinical outcome benefit for coronary revascularization decisions. Both coronary angiographic (anatomic) and functional myocardial imaging have been limited by an inability to reliably estimate physiologic significance determined by FFR. However, advances in computational fluid dynamics have led to interest in FFR estimated by coronary angiograms obtained noninvasively through coronary CT angiography. SUMMARY: The current use of FFRCT has been mostly limited to research applications due to lack of availability and cost, as well as limited outcomes and cost-effectiveness data. Nevertheless, interest remains in the potential role of FFRCT for coronary revascularization treatment decisions, and thus, ongoing and future studies will continue to investigate this technology. PMID- 27652814 TI - Clinical significance of noninvasive coronary flow reserve assessment in patients with ischemic heart disease. AB - PURPOSE OF REVIEW: The importance of physiologic assessments in ischemic heart disease is well recognized. Coronary flow reserve (CFR) is a novel physiologic imaging biomarker that complements both anatomic and semiquantitative perfusion assessments of coronary artery disease (CAD) severity. RECENT FINDINGS: Beyond this, assessment of CFR may provide clinical insights useful for refining diagnosis, prognosis, and eventually, management of patients along the full range of ischemic heart disease phenotypes, from multivessel obstructive CAD to diffuse coronary microvascular dysfunction. SUMMARY: We begin by defining the concept of noninvasive CFR, specifically focusing on quantification of blood flow using PET, for which robust observational data exist. Next, we describe the continuum of cardiovascular risk by CFR values in patients across the anatomic spectrum of CAD, including those with diabetes, chronic kidney disease, and nonobstructive CAD and coronary microvascular dysfunction. Finally, we summarize the impact of CFR on prognosis, with a focus on future directions for management strategies and potential novel therapies, particularly in patients with very low CFR and less obstructive CAD. This latter phenotype may provide a critical link to understanding hidden biological risk of ischemic heart disease in vulnerable populations, including women and patients with heart failure with preserved ejection fraction, metabolic syndrome, cardio-oncologic complications, and inflammatory-related disease. PMID- 27652815 TI - Two-Photon-Induced Isomerization of Spiropyran/Merocyanine at the Air/Water Interface Probed by Second Harmonic Generation. AB - Photochromic molecules often exhibit switchable hyperpolarizabilities upon photoisomerization between two molecular states and can be widely applied in nonlinear optical materials. Photoisomerization can occur through either one photon or two-photon processes. Two-photon-induced isomerization has several advantages over one-photon process but has not been fully explored. In the present study, we have used second harmonic generation to investigate the two photon-induced isomerization between spiropyran and merocyanine at the air/water interface. We show that spiropyran and merocyanine can be converted into each other reversibly with 780-nm laser-beam irradiation through two-photon processes. We also investigated the isomerization rates under various incident laser powers. Quantitative analysis revealed that the isomerization rates of spiropyran and merocyanine depend differently on the laser power. We attribute the difference to the distinct molecular structures of spiropyran and merocyanine. At the interface, nonplanar spiropyran molecules exist mainly as monomers, whereas planar merocyanine molecules form aggregates. Upon aggregation, steric hindrance effects and excitonic coupling efficiently arrest the photoisomerization of merocyanine. This work provides an in-depth understanding of two-photon-induced isomerization at the interface, which is beneficial for designing and controlling optical thin-film materials. PMID- 27652817 TI - New frontiers in interventional cardiology: percutaneous treatment of tricuspid regurgitation. PMID- 27652816 TI - Silent large vegetative mitral-aortic enterococcal endocarditis. AB - : In spite of the evolution of diagnostic and imaging tools, infective endocarditis still remains a challenging diagnostic problem. We report the case of a 77-year-old heart failure patient with a very large mitral vegetative lesion but without fever or any other clinical or microbiological 'endocarditis criteria' except the echocardiographic findings. In this scenario, the second more likely differential diagnosis was neoformation of the mitral valve but despite an exhaustive preoperative diagnostic cardiac imaging, this hypothesis could not be excluded before surgical excision and microbiological examination of the surgical specimen. PMID- 27652818 TI - How important is to reduce sodium and increase potassium in patients with hypertension? PMID- 27652819 TI - NSAIDs and cardiovascular risk. AB - NSAIDs are the most largely used class of drugs in the world, due to their large use in many diseases, in particular for the systemic inflammatory diseases. Nevertheless, today NSAIDs are less used for some of these diseases, due to several side-effects correlated to these drugs. The antiinflammatory mechanism of NSAIDs consist in the inibhition of two forms of cyclooxygenase, namely COX-1 (its block contributes to an antiplatelet effect) and COX-2 (its block has a greater antiinflammatory, antipyretic and analgesic effect). The COX-2 inhibition might reduce the risk of gastrointestinal toxicity, but several studies have shown the cardiovascular side effects of this inhibition. Mechanisms of the cardiovascular side effects are controversial yet, so the aim of this document is to review side-effects profile of NSAIDs and, specifically, to investigate cardiovascular consequences of NSAIDs use in clinical practice. PMID- 27652820 TI - MULTIMODAL IMAGING AND ELECTRORETINOGRAPHY IN LONG-CHAIN 3-HYDROXYACYL COENZYME A DEHYDROGENASE DEFICIENCY. AB - PURPOSE: To report a case of pigmentary retinopathy in long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency using multimodal imaging techniques. METHODS: Case report. RESULTS: An 8-year-old boy with a history of failure to thrive and a diagnosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency was referred for examination. Examination revealed a pigmentary retinopathy with macular atrophy; electroretinography results were consistent with a rod-cone dystrophy. Fundus autofluorescence and optical coherence tomography revealed retinal pigment epithelium atrophy. Follow-up examination findings showed increased severity of retinopathy on electroretinography, with optical coherence tomography angiography revealing enhanced visualization of choroidal vessels. CONCLUSION: This report reveals that long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency can be characterized as a progressive rod-cone dystrophy, with multi-modal imaging techniques used to describe this condition. In particular, optical coherence tomography angiography can be used to further characterize this condition. PMID- 27652821 TI - Full-Color Plasmonic Metasurface Holograms. AB - Holography is one of the most attractive approaches for reconstructing optical images, due to its capability of recording both the amplitude and phase information on light scattered from objects. Recently, optical metasurfaces for manipulating the wavefront of light with well-controlled amplitude, phase, and polarization have been utilized to reproduce computer-generated holograms. However, the currently available metasurface holograms have only been designed to achieve limited colors and record either amplitude or phase information. This fact significantly limits the performance of metasurface holograms to reconstruct full-color images with low noise and high quality. Here, we report the design and realization of ultrathin plasmonic metasurface holograms made of subwavelength nanoslits for reconstructing both two- and three-dimensional full-color holographic images. The wavelength-multiplexed metasurface holograms with both amplitude and phase modulations at subwavelength scale can faithfully produce not only three primary colors but also their secondary colors. Our results will advance various holographic applications. PMID- 27652822 TI - Nazarov Cyclization/Internal Redox Cyclization Sequence for the Synthesis of N Heterocyclic Bridged Ring Systems. AB - A 1,6 conjugate addition/Nazarov electrocyclization/internal redox cyclization sequence was developed. Various 5-hydroxycyclopentenones were made through the 1,6-conjugate addition initiated Nazarov reaction with excellent diastereoselectivities. Under thermal conditions, these underwent a through-space 1,5-hydride-transfer/ring-closure reaction to form bridged bicyclic N heterocyclic compounds with up to four stereogenic centers. It was also possible to convert simple acyclic dienyl diketones into the bicyclo[3.2.1] products in a one-pot process (with a solvent switch). PMID- 27652823 TI - Highly Efficient Thermally Activated Delayed Fluorescence in Dinuclear Ag(I) Complexes with a Bis-Bidentate Tetraphosphane Bridging Ligand. AB - A series of highly emissive neutral dinuclear silver complexes [Ag(PPh3)(X)]2(tpbz) (tpbz = 1,2,4,5-tetrakis(diphenylphosphanyl)benzene; X = Cl (1), Br (2), I (3)) was synthesized and structurally characterized. In the complexes, the silver atoms with tetradedral geometry are bridged by the tpbz ligand, and the ends of the molecules are coordinated by a halogen anion and a terminal triphenylphosphine ligand for each silver atom. These complexes exhibit intense white-blue (lambdamax = 475 nm (1) and 471 nm (2)) and green (lambdamax = 495 nm (3)) photoluminescence in the solid state with quantum yields of up to 98% (1) and emissive decay rates of up to 3.3 * 105 s-1 (1) at 298 K. With temperature decreasing from 298 to 77 K, a red shift of the emission maximum by 9 nm for all these complexes is observed. The temperature dependence of the luminescence for complex 1 in solid state indicates that the emission originates from two thermally equilibrated charge transfer (CT) excited states and exhibits highly efficient thermally activated delayed fluorescence (TADF) at ambient temperature. At 77 K, the decay time is 638 MUs, indicating that the emission is mainly from a triplet state (T1 state). With temperature increasing from 77 to 298 K, a significant decrease of the emissive decay time by a factor of almost 210 is observed, and at 298 K, the decay time is 3.0 MUs. The remarkable decrease of the decay time indicates that thermal population of a short-lived singlet state (S1 state) increases as the temperature increases. The charge transfer character of the excited states and TADF behavior of the complexes are interrogated by DFT and TDDFT calculations. The computational results demonstrate that the origin of TADF can be ascribed to 1,3(ILCT + XLCT+ MLCT) states in complexes 1 and 2 and 1,3(XLCT) states mixed with minor contributions of MLCT and ILCT in complex 3. PMID- 27652824 TI - Acceptability of physiotherapists as primary care practitioners and advanced practice physiotherapists for care of patients with musculoskeletal disorders: a survey of a university community within the province of Quebec. AB - BACKGROUND: Musculoskeletal (MSK) disorders represent a great burden on the health care system. The use of physiotherapists in their autonomous roles and in advanced practice roles may help increase access to care. Thus, the aim of this survey was to assess the perceptions of a university community sample within the province of Quebec about physiotherapists as primary care practitioners and advanced practice physiotherapists (APPs) for the treatment of patients with musculoskeletal disorders. METHODS: An electronic survey was sent in February 2014 via a web platform to members of the Laval University community (Quebec City, Canada). The survey included questions about knowledge and perceptions on current physiotherapists' autonomous role in primary care and on APP future model of care for patients with MSK disorders. Survey results were synthetized with descriptive statistics. Differences in responses according to demographics, personal characteristics and previous physiotherapy care experience were evaluated using Chi-Square tests. RESULTS: A total of 513 participants completed the online survey (1 % response rate). The majority of respondents were women (74 %) and aged 18 to 24 (39 % of all respondent). About 90 % of respondents believed that physiotherapists were skilled and competent and 91 % answered that they had trust in physiotherapists for the treatment of MSK disorders in primary care. A total of 90 % of respondents supported the idea of introducing APPs for the treatment of patients with MSK disorders. Over 90 % of respondents were in favour of the delegation of medical acts such as: communicating a medical diagnosis, ordering imaging tests, triaging surgical candidates or prescribing medication such as NSAIDS. CONCLUSIONS: Respondents are satisfied and have confidence in physiotherapists as primary care practitioners; they also support the intended new roles of the APPs in the health care system. Caution should be taken in generalizing these results from this particular sample. These results need to be corroborated in the general population. PMID- 27652825 TI - Is imatinib a prototypical example of targeted drug therapy? PMID- 27652826 TI - Radiation track, DNA damage and response-a review. AB - The purpose of this paper has been to review the current status and progress of the field of radiation biophysics, and draw attention to the fact that physics, in general, and radiation physics in particular, with the aid of mathematical modeling, can help elucidate biological mechanisms and cancer therapies. We hypothesize that concepts of condensed-matter physics along with the new genomic knowledge and technologies and mechanistic mathematical modeling in conjunction with advances in experimental DNA (Deoxyrinonucleic acid molecule) repair and cell signaling have now provided us with unprecedented opportunities in radiation biophysics to address problems in targeted cancer therapy, and genetic risk estimation in humans. Obviously, one is not dealing with 'low-hanging fruit', but it will be a major scientific achievement if it becomes possible to state, in another decade or so, that we can link mechanistically the stages between the initial radiation-induced DNA damage; in particular, at doses of radiation less than 2 Gy and with structural changes in genomic DNA as a precursor to cell inactivation and/or mutations leading to genetic diseases. The paper presents recent development in the physics of radiation track structure contained in the computer code system KURBUC, in particular for low-energy electrons in the condensed phase of water for which we provide a comprehensive discussion of the dielectric response function approach. The state-of-the-art in the simulation of proton and carbon ion tracks in the Bragg peak region is also presented. The paper presents a critical discussion of the models used for elastic scattering, and the validity of the trajectory approach in low-electron transport. Brief discussions of mechanistic and quantitative aspects of microdosimetry, DNA damage and DNA repair are also included as developed by the authors' work. PMID- 27652827 TI - Identifying adults' valid waking wear time by automated estimation in activPAL data collected with a 24 h wear protocol. AB - The activPAL monitor, often worn 24 h d-1, provides accurate classification of sitting/reclining posture. Without validated automated methods, diaries burdensome to participants and researchers-are commonly used to ensure measures of sedentary behaviour exclude sleep and monitor non-wear. We developed, for use with 24 h wear protocols in adults, an automated approach to classify activity bouts recorded in activPAL 'Events' files as 'sleep'/non-wear (or not) and on a valid day (or not). The approach excludes long periods without posture change/movement, adjacent low-active periods, and days with minimal movement and wear based on a simple algorithm. The algorithm was developed in one population (STAND study; overweight/obese adults 18-40 years) then evaluated in AusDiab 2011/12 participants (n = 741, 44% men, aged >35 years, mean +/- SD 58.5 +/ 10.4 years) who wore the activPAL3TM (7 d, 24 h d-1 protocol). Algorithm agreement with a monitor-corrected diary method (usual practice) was tested in terms of the classification of each second as waking wear (Kappa; kappa) and the average daily waking wear time, on valid days. The algorithm showed 'almost perfect' agreement (kappa > 0.8) for 88% of participants, with a median kappa of 0.94. Agreement varied significantly (p < 0.05, two-tailed) by age (worsens with age) but not by gender. On average, estimated wear time was approximately 0.5 h d-1 higher than by the diary method, with 95% limits of agreement of approximately this amount +/-2 h d-1. In free-living data from Australian adults, a simple algorithm developed in a different population showed 'almost perfect' agreement with the diary method for most individuals (88%). For several purposes (e.g. with wear standardisation), adopting a low burden, automated approach would be expected to have little impact on data quality. The accuracy for total waking wear time was less and algorithm thresholds may require adjustments for older populations. PMID- 27652828 TI - Sacrospinous ligament suspension with transobturator mesh versus sacral colpopexy for genital prolapse. AB - OBJECTIVE: To compare the safety and efficacy of abdominal sacral colpopexy and sacrospinous ligament suspension with the use of vaginal mesh for apical prolapse. METHOD: This retrospective study was conducted from 2005 to 2012 and included 89 women with apical prolapse who underwent surgery. Assessments included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage. Rates of objective cure and immediate/late complications were compared. RESULTS: In total, 41 of the 89 women underwent sacrospinous ligament suspension, and 48 of the women underwent abdominal sacral colpopexy. A total of 40.4% of the women had vault prolapse (p=0.9361). Most of them had no complications (93.2%) (p=0.9418). Approximately 30% of the women had late complications; local pain was the main symptom and was found only in women who underwent the abdominal procedure (25.6%) (p=0.001). Only the women who were submitted to the vaginal procedure had mesh exposure (18.4%). The objective success rate and the rate of anterior vaginal prolapse (p=0.2970) were similar for both techniques. CONCLUSION: Sacrospinous ligament suspension was as effective and had a similar objective success rate as abdominal sacral colpopexy for the treatment of apical prolapse. Sacrospinous ligament suspension performed with the use of vaginal mesh in the anterior compartment was effective in preventing anterior vaginal prolapse after surgery. PMID- 27652829 TI - Hypertension and arterial stiffness in heart transplantation patients. AB - OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension. PMID- 27652830 TI - Mothers' conceptions about excess weight in infancy and the nutritional status of their children. AB - OBJECTIVE: To analyze maternal conceptions about excess weight in infancy and the nutritional status of their preschool-aged children. METHODS: A mixed, exploratory study was performed using semi-structured interviews. Two study groups were defined: a group of 16 mothers of children with excess weight and a group of 15 mothers of eutrophic children. The interviews were submitted to content analysis using CHIC software (Classification Hierarchique Implicative et Cohesitive-). RESULTS: The mothers of children with excess weight tended to conceive thin children as malnourished, while those of normal weight children emphasized the influence of family and genetics as determinants of a child's nutritional status. Although there was a certain consensus among the mothers that an unhealthy diet contributes to the risk of a child developing excess weight, the concept of genetics as a determinant of a child's nutritional status was also present in the dialogue from the mothers of both groups. This result indicates a lack of clarity regarding the influence of eating behavior and family lifestyle on weight gain and the formation of a child's eating habits. Both groups indicated that the mother has a decisive role in the eating habits of her child; however, the mothers of children with excess weight did not seem to take ownership of this concept when addressing the care of their own children. CONCLUSION: Differences in conceptions, including taking ownership of care, may contribute to the development of excess weight in preschool-aged children. PMID- 27652831 TI - Is polysomnographic examination necessary for subjects with diaphragm pathologies? AB - OBJECTIVES: While respiratory distress is accepted as the only indication for diaphragmatic plication surgery, sleep disorders have been underestimated. In this study, we aimed to detect the sleep disorders that accompany diaphragm pathologies. Specifically, the association of obstructive sleep apnea syndrome with diaphragm eventration and diaphragm paralysis was evaluated. METHODS: This study was performed in Sureyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital between 2014-2016. All patients had symptoms of obstructive sleep apnea (snoring and/or cessation of breath during sleep and/or daytime sleepiness) and underwent diaphragmatic plication via video-assisted mini thoracotomy. Additionally, all patients underwent pre- and postoperative full night polysomnography. Pre- and postoperative clinical findings, polysomnography results, Epworth sleepiness scale scores and pulmonary function test results were compared. RESULTS: Twelve patients (7 males) with a mean age of 48 (range, 27-60) years and a mean body mass index of 25 (range, 20-30) kg/m2 were included in the study. Preoperative polysomnography showed obstructive sleep apnea syndrome in 9 of the 12 patients (75%), while 3 of the patients (25%) were regarded as normal. Postoperatively, patient complaints, apnea hypopnea indices, Epworth sleepiness scale scores and pulmonary function test results all demonstrated remarkable improvement. CONCLUSION: All patients suffering from diaphragm pathologies with symptoms should undergo polysomnography, and patients diagnosed with obstructive sleep apnea syndrome should be operated on. In this way, long-term comorbidities of sleep disorders may be prevented. PMID- 27652832 TI - Prenatal natural history of isolated fetal mild bilateral pyelectasis. AB - OBJECTIVE: To analyze the prenatal outcomes in a cohort of fetuses with mild bilateral pyelectasis and determine whether performing serial ultrasounds is a good follow-up strategy. METHODS: A prospective longitudinal study was conducted on 62 fetuses with mild bilateral pyelectasis. Fetal mild bilateral pyelectasis was considered when the renal pelvis measured (in millimeters) >=5.0 to 10.0, >=7.0 to 10.0, and >=10.0 to 15 at <=23 weeks 6 days, 24 to 31 weeks 6 days, and >=32 weeks, respectively, with no uretero-calyceal dilatation. Ultrasounds were performed every 3 weeks to assess whether the mild bilateral pyelectasis regressed, remained unchanged (Group 1) or progressed (Group 2). RESULTS: Group 1 consisted of 53 fetuses (85.4%), and progression was observed in 9 cases (Group 2, 14.6%). The initial renal pelvis diameter was significantly larger in fetuses with progression (p=0.028). Statistically significant differences in the renal pelvis diameter were also found at weeks 31 and 35 for both kidneys (p<0.05). The cases requiring intrauterine procedures or early delivery were not observed. CONCLUSION: Fetal mild bilateral pyelectasis with no calyceal dilatation is a benign condition that can be managed in the postnatal period. The initial renal pelvis diameter and the diameter in week 31 or 35 were valuable parameters for identifying cases that would eventually need specific postnatal procedures. PMID- 27652833 TI - Peak expiratory flow mediates the relationship between handgrip strength and timed up and go performance in elderly women, but not men. AB - OBJECTIVE: The aim of the present study was to verify if there is sex difference in the associations among handgrip strength, peak expiratory flow (PEF) and timed up and go (TUG) test results. METHODS: The sample included 288 consecutive elderly men (n=93) and women (n=195). Functional capacity was measured using the TUG test, and muscle strength was measured based on handgrip. Moreover, as a measure of current health status, PEF was evaluated. Linear regression procedures were performed to analyze the relationships between handgrip and both PEF and TUG test results, with adjustment for confounders, and to identify the possible mediating role of PEF in the association between handgrip strength and TUG test results. RESULTS: In men, handgrip strength was associated with both PEF and TUG performance (p<0.01). After adjustment for PEF, the relationship between handgrip strength and TUG performance remained significant. In women, handgrip strength was also associated with both PEF and TUG performance (p<0.01). However, after adjustment for PEF, the relationship between handgrip strength and TUG performance was no longer significant. CONCLUSION: Mobility in the elderly is sex dependent. In particular, PEF mediates the relationship between handgrip strength and TUG performance in women, but not in men. PMID- 27652834 TI - Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy. AB - OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure. PMID- 27652835 TI - Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue? AB - OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats. PMID- 27652836 TI - Review of developments in corneal transplantation in the regions of Brazil - Evaluation of corneal transplants in Brazil. AB - The aim of this study was to identify inequalities in corneal donation and transplantation among the regions of Brazil. A transversal and retrospective study was specifically conducted using data from the Brazilian Transplant Registry collected by the Brazilian Association of Organ Transplantation between January 2002 and December 2014. The collected data were processed using descriptive statistical methods, and p<0.05 was the rate of rejection of the null hypothesis. From 2002 to 2014, there was an increase in the absolute number of corneal transplants, the annual rate of transplants per million people and the percentage of needed transplants performed in each of the five regions of Brazil. Family refusal and medical contraindication were the most frequent reasons for a lack of corneal donation. Although remarkable progress has been made in the last decade in each of the five Brazilian regions, health professionals' lack of preparation to approach families with donation requests at the death of a family member appears to be the main obstacle to increasing the number of corneal donations. Thus, the present study suggests the implementation of public policies to make corneal transplants more effective, particularly given that there are considerable disparities in the effectiveness with which regional needs are met and in health professionals' ability to perform transplants among the Brazilian regions, with higher rates in the South, Southeast and Midwest regions and lower rates in the North and Northeast regions. PMID- 27652837 TI - Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia reperfusion injury? AB - Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID- 27652839 TI - Estimates of first-generation women and girls with female genital mutilation in the European Union, Norway and Switzerland. AB - BACKGROUND: Female genital mutilation (FGM) is the practice of partial or total removal of female genitalia for non-medical reasons. The procedure has no known health benefits but can cause serious immediate and long-term obstetric, gynaecological and sexual health problems. Health workers in Europe are often unaware of the consequences of FGM and lack the knowledge to treat women adequately. OBJECTIVE: Our goal was to estimate the number of first-generation girls and women in the European Union, Norway and Switzerland who have undergone FGM. Before migration from FGM-practicing countries began, FGM was an unknown phenomenon in Europe. METHODS: Secondary analysis of data from the 2011 EU census and extrapolation from age-specific FGM prevalence rates in the immigrants' home countries to these data were used to provide our estimates. Estimates based on census and other demographic data were compared to our results for Belgium. RESULTS: In 2011 over half a million first-generation women and girls in the EU, Norway and Switzerland had undergone FGM before immigration. One in two was living in the UK or France, one in two was born in East-Africa. CONCLUSIONS: For the first time, scientific evidence gives a reliable estimate of the number of first-generation women and girls in Europe coming from countries where FGM is practiced. The use of census data proves reliable for policy makers to guide their actions, e.g., regarding training needs for health workers who might be confronted with women who have undergone FGM, or the need for reconstructive surgery. PMID- 27652838 TI - Clinical features and outcomes of diffuse endocapillary proliferation Henoch Schonlein purpura nephritis in children. AB - OBJECTIVE: To investigate the outcomes of childhood diffuse endocapillary proliferation Henoch-Schonlein purpura nephritis (DEP-HSPN) in response to early diagnosis and prompt treatment. METHODS: Eleven cases of DEP-HSPN in children were investigated in comparison to HSPN without diffuse endocapillary proliferation (non-DEP-HSPN). RESULTS: DEP-HSPN had a higher prevalence of nephrotic syndrome but a lower prevalence of hematuria compared to non-DEP-HSPN. IgA, IgG and IgM antibody deposition was found in DEP-HSPN by histopathological examination. Proteinuria cleared in all 11 cases through treatment with steroids and/or immunosuppressive drugs. However, half of the DEP-HSPN patients continuously had hematuria after treatment. CONCLUSION: The early diagnosis and prompt initiation of immunosuppressive treatment based on renal biopsy are important for achieving favorable outcomes. PMID- 27652841 TI - Success story. AB - The development of the role of the specialist continence adviser hits been one of the greatest success stories of the profession. Any reservations expressed in the early days that the role was superfluous have long been overcome. Continence advisers have played a major part in altering the emphasis of care from passive management of incontinence to positive attempts to promote continence. They have earned the gratitude of countless clients and the respect of their colleagues. PMID- 27652840 TI - Epilepsy and electroencephalographic abnormalities in C9orf72 repeat expansion. AB - A patient has been recently described with frontotemporal cognitive decline and C9orf72 repeat expansion who presented abnormally slowed background and photoparoxysmal response at electroencephalographic (EEG) recording. Our data, based on five patients with repeat expansions in C9orf72 and EEG recordings suggest that abnormally slowed background and epilepsy represent previously unrecognized features of the C9orf72 phenotype in some patients. PMID- 27652842 TI - How European are you? AB - Green issues have been nudged from the top of the small-talk hit list: it's far more fashionable now to have a view on Europe. With Sir Geoffrey Howe joining the growing band of deserters from the Tory camp over the vexed European question, chasms in the Cabinet have resulted in divisions at the dinner table. But Sir Geoffrey's walk-out came at the end of a week when euphoria mingled with indignation as France and Britain were linked by the Channel Tunnel. Shock waves rippled through the country with the realisation that Britain is 'no longer an island'. The euphoria had more to do with the glimmer of hope that the 'Chunnel was at some stage going to reach its objective. PMID- 27652843 TI - Prescribing rights. AB - The report of the advisory group on nurse prescribing (1) has met a mixed response from continence advisers. There is much to be welcomed in this report which, if implemented, will undoubtedly improve many aspects of patient care. In this interim period between the end of the consultation exercise and the issue of any revisions based upon that consultation, it is impossible to know what the final terms of nurse prescribing will be. If implemented unchanged, some serious anomalies and problems can be foreseen. PMID- 27652844 TI - Nurses stop work to protest captivity. AB - British and Irish nurses held hostage in Iraq have stopped work at one of Baghdad's largest hospitals, in protest at not being allowed home. PMID- 27652845 TI - Education changes to be funded by DoH? AB - There were hints last week that major changes in post-registration education could be funded by extra cash from the Government. PMID- 27652846 TI - Clarke moved from Health Department. AB - Kenneth Clarke's surprise departure from the Department of Health in last week's Cabinet reshuffle met a mixed reaction from nursing organisations. PMID- 27652847 TI - Nursing care audit. AB - A new nursing audit initiative was launched last week to teach all grass-roots staff how to measure the quality of their care. PMID- 27652848 TI - What prescribing powers mean. AB - From April 1992 it has been recommended that nurses working in the community will be able to prescribe from a Nurses' Formulary a limited list of drugs, dressings, appliances and chemical reagents ( 1 ). This article describes some of the key recommendations from the report, discusses their implications for continence advisers and presents the necessary educational initiatives required for continence advisers to prepare themselves for these changes. PMID- 27652850 TI - Overweight nurses given slim chance of work. AB - Overweight nurses applying for jobs in Cleveland have been told they are not fit enough for work on the wards, it was revealed last week. PMID- 27652851 TI - ? AB - Pictured at the launch of the Maternity Alliance/Persil hirthplan and midwives' teaching notes are (left to right) Jennette Golding, RCN Adviser to the General Secretary on Race and Ethnicity: Dr Miriam Stoppard; and Angela Phillips, MA Vice chair. PMID- 27652852 TI - Era of practice nursing 'beckons health visitors'. AB - More health visitors are likely to become practice nurses or be employed by GPs in future, Health Minister Virginia Bottomley predicted last week. PMID- 27652853 TI - ? AB - Patient services, the National Health Service reforms and clinical grading were on the agenda when labour's Chief Spokesman for Wales, MP Barry Jones, visited the Royal College of Nursing Welsh Board recently. Nurses told Mr Jones about their concerns over waiting lists and said no hospital should become an NHS Trust unless there are real benefits for the community. He is pictured with Anne Pegington. Board Secretary, left, and Chairman Meg Edwards. PMID- 27652854 TI - Nurses 'must not be loss leaders' in pay rounds. AB - Nurses must not be used as 'loss leaders' by the Government in its attempt to keep wages down in the economy as a whole, RCN General Secretary Christine Hancock has told Employment Secretary Michael Howard. PMID- 27652855 TI - Call for stronger nursing links in Europe. AB - United Kingdom nurses share the same concerns and hopes for the future as their European colleagues, according to new research findings. PMID- 27652857 TI - 'Children suffer' due to undertreatment by nurses. AB - Older children are suffering unnecessarily in hospital because nurses underestimate the pain they feel, a Dutch child psychologist said last week. PMID- 27652856 TI - Deprived Welsh areas targeted for community care. AB - A project which targets the work of community nurses in deprived parts of Wales was launched last week. PMID- 27652858 TI - ? AB - Footballer Garth Crooks was one of the guest speakers at a Camberwell Community Health Council public meeting on the treatment of patients with sickle cell anaemia last week. He is pictured with Sandra Gordon, who chaired the meeting. PMID- 27652859 TI - Nurses told to mobilise for future. AB - Working with elderly people is nursing's greatest challenge and one of the biggest political issues confronting the profession, according to Professor June Clark, RCN President Elect. PMID- 27652861 TI - Parliament. AB - Hopes of funding community care for mentally ill or handicapped people through large land sales are set to be dashed according to the Commons Social Services Committee. PMID- 27652860 TI - Trophic stimulation. AB - Recent research papers show that the female pelvic floor muscles make stereotypical adaptations to poor usage, pain and in some 50 per cent of cases studies pudendal nerve lesion. These adaptations involve a selective loss of the deep muscle fibres which give the pelvic floor the postural tone to support the weight of the pelvic contents. They have also been shown to aid in the transmission of abdominal pressure increase during coughing and sneezing to support the external sphincter and allow the superficial, fast-acting fibres to have maximal efficiency in preventing urine leakage. PMID- 27652862 TI - Catheter choice. AB - While catheterisation is usually a medical decision, in the community setting it is frequently the district nurse who selects the catheter with advice from the local continence adviser. With nurse prescribing on the horizon, those of us responsible for selection should make use of relevant research to ensure we choose the correct product for our patients and clients. The Nursing Practice Research Unit report ( 1 ) on procedures for catheter care made several recommendations, including. PMID- 27652863 TI - More training needed for fertility nurses. AB - Two thirds of fertility nurses believe they need specialised training in order to carry out many of the tasks expected of them, a major survey has revealed. PMID- 27652864 TI - New cancer test to undergo trials. AB - A new test to detect early cancers from blood samples is to be introduced at Southampton General Hospital as part of an international trial next year. PMID- 27652866 TI - Dispensing advice. AB - Helen Ball and Joy Chapman are, respectively, the centre manager and an appliance practice nurse (APN) at the Thackraycare dispensing appliance centre in Wolverhampton. Both are qualified RGNs who joined the company from posts within the health service. PMID- 27652868 TI - Project 2000 may face stumbling block. AB - Fear of change among the hierarchies in nursing could present a major stumbling block to the success of Project 2000, the new RCN Director of Education Tom Bolger believes. PMID- 27652869 TI - Struggling towards the thinking practitioner. AB - Nursing must rid itself of its traditional task-orientated approach to practice and its over-obsession with rules, according to leading nurse educator Professor Maureen Lahitf. PMID- 27652870 TI - NHS reforms viewed as harmful to nurses. AB - Former Royal College of Nursing General Secretary Trevor Clay slammed the NHS reforms and claimed it would be one of the major issues at the next general election. PMID- 27652872 TI - Cutting down on decibels. AB - Noise pollution is an ever-increasing problem in the hospital environment, which can be both distressing and damaging to health. PMID- 27652871 TI - Linking study, education and practice. AB - If you are the kind of nurse who thinks study is only for students, the launch last week of the UK Central Council's major report on continuing education could leave you deeply shaken. PMID- 27652873 TI - Give peace a chance. AB - After eight weeks in hospital, Mrs Gertrude Apthorpe, is serene and charming despite having suffered several sleepless nights due to bed pumps creaking, chairs screeching across the floor and nurses carrying out their usual night routines. PMID- 27652874 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should be sent to us on an official listings form and contain all relevant details. Listings forms can be obtained from Clare Ward at Nursing Standard, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. PMID- 27652875 TI - Registering dismay. AB - Although I did note that Richard Miller's Debate article ('Abolish RMN Specialisms', Nursing Standard, October 24) was intended to be provocative, I had to read his article twice and then check the date to make sure it wasn't an April Fool's joke. PMID- 27652876 TI - ? PMID- 27652877 TI - Specialism sadness. AB - I am somewhat saddened by Richard Miller's apparently well researched article ('Abolish RMN Specialisms', ! Nursing Standard October 24). PMID- 27652878 TI - Professional status. AB - In response to D J Brown's letter Professional recognition' (Nursing Standard October 24). PMID- 27652879 TI - The wrong reign. AB - Astute readers will have noticed that in last week's nursing history article, 'Waiting for the Bombs to Fall', we catapulted the reigning monarch back in time. King George VI became King George IV due to an error of transposition. We apologise to the author, Dame Kathleen Raven for any embarrassment. PMID- 27652880 TI - Trained anger. AB - I read with dismay the letter Helpers must support nurses' (Nursing Standard October 24). Here we go again - 'I am trained you are not' - the I am a trained nurse syndrome'. PMID- 27652881 TI - Information exchange. AB - I and other interested colleagues are planning to initiate a Cognitive Behavioural Therapy Interest Group in our district. PMID- 27652882 TI - Issue of the moment. AB - Current media attention to the Graham Pink case has implied that nursing academics and researchers (among others) fail to get involved in the issues of the moment, namely the struggle for resources and power. As a result, it is claimed, informed commentary from this section of the nursing community is noteable by its absence. PMID- 27652883 TI - Answers to last week's crossword. PMID- 27652885 TI - Unity is strength. AB - The nursing profession finally appears to be waking up to the reality of that new breed of community nurse - the practice nurse. PMID- 27652884 TI - Points of view. AB - About a year ago, when the ' billboard adverts declaring 'Drugs - the effects can last forever' first appeared, I thought: 'Oh good, at last someone is having a go at the pharmaceutical industry for the way it markets dangerous drugs.' PMID- 27652886 TI - Effect of graphene oxide ratio on the cell adhesion and growth behavior on a graphene oxide-coated silicon substrate. AB - Control of living cells on biocompatible materials or on modified substrates is important for the development of bio-applications, including biosensors and implant biomaterials. The topography and hydrophobicity of substrates highly affect cell adhesion, growth, and cell growth kinetics, which is of great importance in bio-applications. Herein, we investigate the adhesion, growth, and morphology of cultured breast cancer cells on a silicon substrate, on which graphene oxides (GO) was partially formed. By minimizing the size and amount of the GO-containing solution and the further annealing process, GO-coated Si samples were prepared which partially covered the Si substrates. The coverage of GO on Si samples decreases upon annealing. The behaviors of cells cultured on two samples have been observed, i.e. partially GO-coated Si (P-GO) and annealed partially GO-coated Si (Annealed p-GO), with a different coverage of GO. Indeed, the spreading area covered by the cells and the number of cells for a given culture period in the incubator were highly dependent on the hydrophobicity and the presence of oxygenated groups on GO and Si substrates, suggesting hydrophobicity-driven cell growth. Thus, the presented method can be used to control the cell growth via an appropriate surface modification. PMID- 27652887 TI - Drug-Loaded Nanoparticles Embedded in a Biomembrane Provide a Dual-Release Mechanism for Drug Delivery to the Eye. AB - PURPOSE: Topical delivery by eye drops, which accounts for ~90% of all ophthalmic formulations, is inefficient for drug delivery to the posterior segment. Only 5% of the drug applied as drops reaches the target, whereas the rest is lost through tear drainage. A number of conditions such as glaucoma and proliferative retinopathy need sustained drug release to be therapeutically effective. The purpose of this study was to develop a novel dual-release drug delivery system to meet this requirement. METHODS: Our system consists of lidocaine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles suspended within a thin collagen membrane. This system provides constant contact with the cornea, and the nanoparticles supply a continuous release of medication, resulting in more drug reaching the target. This system provides dual release of the drug, from both the nanoparticles and the membrane. RESULTS: The nanoparticles loaded into the membrane did not have a significant effect on light transmittance through the membrane compared with a commercial contact lens. The membranes containing nanoparticles showed a lesser burst release of 16.2% of the initial lidocaine loading than the free nanoparticles with a burst release of 41.8% of the initial lidocaine loading. The membrane containing nanoparticles showed a slow and continuous release of lidocaine of up to 23.4% of the initial loading after 7 days compared with 64% for the free nanoparticles. CONCLUSIONS: The dual-release membrane system shows promise for a new drug delivery method to the eye with limited burst release and sustained delivery. PMID- 27652888 TI - Curli mediate bacterial adhesion to fibronectin via tensile multiple bonds. AB - Many enteric bacteria including pathogenic Escherichia coli and Salmonella strains produce curli fibers that bind to host surfaces, leading to bacterial internalization into host cells. By using a nanomechanical force-sensing approach, we obtained real-time information about the distribution of molecular bonds involved in the adhesion of curliated bacteria to fibronectin. We found that curliated E. coli and fibronectin formed dense quantized and multiple specific bonds with high tensile strength, resulting in tight bacterial binding. Nanomechanical recognition measurements revealed that approximately 10 bonds were disrupted either sequentially or simultaneously under force load. Thus the curli formation of bacterial surfaces leads to multi-bond structural components of fibrous nature, which may explain the strong mechanical binding of curliated bacteria to host cells and unveil the functions of these proteins in bacterial internalization and invasion. PMID- 27652889 TI - Distinct and Overlapping Requirements for Cyclins A, B, and B3 in Drosophila Female Meiosis. AB - Meiosis, like mitosis, depends on the activity of the cyclin dependent kinase Cdk1 and its cyclin partners. Here, we examine the specific requirements for the three mitotic cyclins, A, B, and B3 in meiosis of Drosophila melanogaster We find that all three cyclins contribute redundantly to nuclear envelope breakdown, though cyclin A appears to make the most important individual contribution. Cyclin A is also required for biorientation of homologs in meiosis I. Cyclin B3, as previously reported, is required for anaphase progression in meiosis I and in meiosis II. We find that it also plays a redundant role, with cyclin A, in preventing DNA replication during meiosis. Cyclin B is required for maintenance of the metaphase I arrest in mature oocytes, for spindle organization, and for timely progression through the second meiotic division. It is also essential for polar body formation at the completion of meiosis. With the exception of its redundant role in meiotic maturation, cyclin B appears to function independently of cyclins A and B3 through most of meiosis. We conclude that the three mitotic cyclin-Cdk complexes have distinct and overlapping functions in Drosophila female meiosis. PMID- 27652890 TI - Genomic Prediction of Resistance to Pasteurellosis in Gilthead Sea Bream (Sparus aurata) Using 2b-RAD Sequencing. AB - Gilthead sea bream (Sparus aurata) is a species of paramount importance to the Mediterranean aquaculture industry, with an annual production exceeding 140,000 metric tons. Pasteurellosis due to the Gram-negative bacterium Photobacterium damselae subsp. piscicida (Phdp) causes significant mortality, especially during larval and juvenile stages, and poses a serious threat to bream production. Selective breeding for improved resistance to pasteurellosis is a promising avenue for disease control, and the use of genetic markers to predict breeding values can improve the accuracy of selection, and allow accurate calculation of estimated breeding values of nonchallenged animals. In the current study, a population of 825 sea bream juveniles, originating from a factorial cross between 67 broodfish (32 sires, 35 dams), were challenged by 30 min immersion with 1 * 105 CFU virulent Phdp. Mortalities and survivors were recorded and sampled for genotyping by sequencing. The restriction-site associated DNA sequencing approach, 2b-RAD, was used to generate genome-wide single nucleotide polymorphism (SNP) genotypes for all samples. A high-density linkage map containing 12,085 SNPs grouped into 24 linkage groups (consistent with the karyotype) was constructed. The heritability of surviving days (censored data) was 0.22 (95% highest density interval: 0.11-0.36) and 0.28 (95% highest density interval: 0.17 0.4) using the pedigree and the genomic relationship matrix respectively. A genome-wide association study did not reveal individual SNPs significantly associated with resistance at a genome-wide significance level. Genomic prediction approaches were tested to investigate the potential of the SNPs obtained by 2b-RAD for estimating breeding values for resistance. The accuracy of the genomic prediction models (r = 0.38-0.46) outperformed the traditional BLUP approach based on pedigree records (r = 0.30). Overall results suggest that major quantitative trait loci affecting resistance to pasteurellosis were not present in this population, but highlight the effectiveness of 2b-RAD genotyping by sequencing for genomic selection in a mass spawning fish species. PMID- 27652891 TI - The Selective Maintenance of Allelic Variation Under Generalized Dominance. AB - Simple models of viability selection acting on variation at a single diploid locus only maintain multiple alleles for very restricted sets of fitnesses. Most of these models assume that fitnesses are independent, even if the genotypes share alleles. Here, we extend this result to a model with generalized dominance interactions, in which fitnesses are strongly affected by what we call the "primary effects" of the genotype's component alleles, so that genotypes with shared alleles have correlated fitnesses. Nevertheless, in keeping with previously reported results, we also show that such fitness sets are easily constructed over time if recurrent mutation is occurring simultaneously. We find that such models maintain less variation over time than do (previous) models with independently sampled fitnesses, especially when the effects of genetic drift are taken into account. We also show that there is a weak tendency for greater weighting of primary effects to evolve over time. PMID- 27652893 TI - Inversion of diffraction data for amorphous materials. AB - The general and practical inversion of diffraction data-producing a computer model correctly representing the material explored-is an important unsolved problem for disordered materials. Such modeling should proceed by using our full knowledge base, both from experiment and theory. In this paper, we describe a robust method to jointly exploit the power of ab initio atomistic simulation along with the information carried by diffraction data. The method is applied to two very different systems: amorphous silicon and two compositions of a solid electrolyte memory material silver-doped GeSe3. The technique is easy to implement, is faster and yields results much improved over conventional simulation methods for the materials explored. By direct calculation, we show that the method works for both poor and excellent glass forming materials. It offers a means to add a priori information in first-principles modeling of materials, and represents a significant step toward the computational design of non-crystalline materials using accurate interatomic interactions and experimental information. PMID- 27652892 TI - Extensive Epigenetic Changes Accompany Terminal Differentiation of Mouse Hepatocytes After Birth. AB - DNA methylation is traditionally thought to be established during early development and to remain mostly unchanged thereafter in healthy tissues, although recent studies have shown that this epigenetic mark can be more dynamic. Epigenetic changes occur in the liver after birth, but the timing and underlying biological processes leading to DNA methylation changes are not well understood. We hypothesized that this epigenetic reprogramming was the result of terminal differentiation of hepatocyte precursors. Using genomic approaches, we characterized the DNA methylation patterns in mouse liver from E18.5 until adulthood to determine if the timing of the DNA methylation change overlaps with hepatocyte terminal differentiation, and to examine the genomic context of these changes and identify the regulatory elements involved. Out of 271,325 CpGs analyzed throughout the genome, 214,709 CpGs changed DNA methylation by more than 5% (e.g., from 5 to 10% methylation) between E18.5 and 9 wk of age, and 18,863 CpGs changed DNA methylation by more than 30%. Genome-scale data from six time points between E18.5 and P20 show that DNA methylation changes coincided with the terminal differentiation of hepatoblasts into hepatocytes. We also showed that epigenetic reprogramming occurred primarily in intergenic enhancer regions while gene promoters were less affected. Our data suggest that normal postnatal hepatic development and maturation involves extensive epigenetic remodeling of the genome, and that enhancers play a key role in controlling the transition from hepatoblasts to fully differentiated hepatocytes. Our study provides a solid foundation to support future research aimed at further revealing the role of epigenetics in stem cell biology. PMID- 27652895 TI - 2016 APMA Annual Scientific Meeting (The National) Abstract Competition Winners. PMID- 27652894 TI - A basal ganglia circuit for evaluating action outcomes. AB - The basal ganglia, a group of subcortical nuclei, play a crucial role in decision making by selecting actions and evaluating their outcomes. While much is known about the function of the basal ganglia circuitry in selection, how these nuclei contribute to outcome evaluation is less clear. Here we show that neurons in the habenula-projecting globus pallidus (GPh) in mice are essential for evaluating action outcomes and are regulated by a specific set of inputs from the basal ganglia. We find in a classical conditioning task that individual mouse GPh neurons bidirectionally encode whether an outcome is better or worse than expected. Mimicking these evaluation signals with optogenetic inhibition or excitation is sufficient to reinforce or discourage actions in a decision-making task. Moreover, cell-type-specific synaptic manipulations reveal that the inhibitory and excitatory inputs to the GPh are necessary for mice to appropriately evaluate positive and negative feedback, respectively. Finally, using rabies-virus-assisted monosynaptic tracing, we show that the GPh is embedded in a basal ganglia circuit wherein it receives inhibitory input from both striosomal and matrix compartments of the striatum, and excitatory input from the 'limbic' regions of the subthalamic nucleus. Our results provide evidence that information about the selection and evaluation of actions is channelled through distinct sets of basal ganglia circuits, with the GPh representing a key locus in which information of opposing valence is integrated to determine whether action outcomes are better or worse than expected. PMID- 27652896 TI - The putative flavin carrier family FlcA-C is important for Aspergillus fumigatus virulence. AB - Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. The signaling by calcium is very important for A. fumigatus pathogenicity and it is regulated by the transcription factor CrzA. We have previously used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA. We have identified among several genes regulated by calcium stress, the putative flavin transporter, flcA. This transporter belongs to a small protein family composed of FlcA, B, and C. The DeltaflcA null mutant showed several phenotypes, such as morphological defects, increased sensitivity to calcium chelating-agent ethylene glycol tetraacetic acid (EGTA), cell wall or oxidative damaging agents and metals, repre-sentative of deficiencies in calcium signaling and iron homeostasis. Increasing calcium concentrations improved significantly the DeltaflcA growth and conidiation, indicating that DeltaflcA mutant has calcium insufficiency. Finally, DeltaflcA-C mutants showed reduced flavin adenine dinucleotide (FAD) and were avirulent in a low dose murine infection model. PMID- 27652898 TI - Overview of the potent cyanobacterial neurotoxin beta-methylamino-L-alanine (BMAA) and its analytical determination. AB - Blue-green algae are responsible for the production of different types of toxins which can be neurotoxic, hepatotoxic, cytotoxic and dermatotoxic and that can affect both aquatic and terrestrial life. Since its discovery the neurotoxin beta methylamino-L-alanine (BMAA) has been a cause for concern, being associated with the neurodegenerative disease amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC). The initial focus was on Guam where it was observed that a high number of people were affected by the ALS/PDC complex. Subsequently, researchers were surprised to find levels of BMAA in post mortem brains from Canadian patients who also suffered from ALS/PDC. Recent research demonstrates that BMAA has been found at different levels in the aquatic food web in the brackish waters of the Baltic Sea. There is emerging evidence to suggest that sand-borne algae from Qatar can also contain BMAA. Furthermore, there is now concern because BMAA has been found not only in warmer regions of the world but also in temperate regions like Europe. The aim of this review is to focus on the methods of extraction and analysis of the neurotoxic non-protein amino acid BMAA. We also consider the neurotoxicity, aetiology, and diverse sources and routes of exposure to BMAA. In recent years, different methods have been developed for the analysis of BMAA. Some of these use HPLC-FD, UPLC-UV, UPLC-MS and LC-MS/MS using samples that have been derivatised or underivatised. To date the LC-MS/MS approach is the most widely used analytical technique as it is the most selective and sensitive method for BMAA determination. PMID- 27652897 TI - BMI-specific associations between health-related behaviours and overweight - a longitudinal study among Norwegian adolescents. AB - OBJECTIVE: To investigate BMI-specific associations between health-related behaviours in early adolescence and the likelihood of overweight in mid adolescence in a sample of Norwegian adolescents. DESIGN: Longitudinal study of 393 adolescents recruited from schools in Telemark County, Norway. Parents reported baseline data on children's behavioural variables and background data (at age 12-13 years). Dietary data were reported by means of a retrospective FFQ. Eating patterns were identified using principal component analysis. Height and weight were measured at baseline and 3-year follow-up. BMI-specific differences in health-related behaviours (eating patterns, physical activity and screen time) at baseline were analysed using cross-tabulation and Pearson's chi 2 test (Fisher's test). Associations between early health-related behaviours and the likelihood of later overweight were examined using multiple logistic regression. SETTING: Primary and secondary schools, Telemark, Norway. SUBJECTS: Children (n 393) in 7th grade (mean age 12.7 (sd 0.3) years), followed up in 10th grade, and parents. RESULTS: A moderate to high intake of a varied Norwegian eating pattern combined with moderate-to-vigorous physical activity >=1 h/d in the 7th grade were associated with a reduced likelihood of being overweight in the 10th grade, but only among already overweight adolescents (adjusted OR=0.2; 95 % CI 0.1, 1.0). Screen time of >3 h/d in the 7th grade was associated with an increased likelihood of subsequent overweight only among adolescents with an initial normal weight (adjusted OR=2.8; 95 % CI 1.1, 7.3). CONCLUSIONS: BMI-specific associations were observed between health-related behaviours in early adolescence and the likelihood of being overweight in mid-adolescence. PMID- 27652899 TI - The frequency and outcome of acute dyspnoea in primary care: An observational study. AB - BACKGROUND: Little is known about the occurrence of acute dyspnoea in primary care and its underlying causes. OBJECTIVES: What are the occurrence and most frequent causes of acute dyspnoea in primary care, predictors of referral, hospitalization, death and possible underlying causes? METHODS: Twenty-five general practitioners (GPs) in Flanders (Belgium) recorded patient contacts for four periods of two weeks during one year. They recorded patients presenting with acute dyspnoea, location of contact (surgery versus home visit), new dyspnoea versus exacerbation, tentative diagnosis, referral to a specialist and hospital, and one month later final diagnosis, its justification, referral, hospitalization and death. RESULTS: Twenty-two GPs recorded 14,620 patient contacts. Acute dyspnoea was encountered in 317 patient-doctor contacts (2.2%; 95%CI: 1.9-2.4), without significant association between the acute dyspnoea frequency, and age and gender. Immediate referral and hospitalization were most frequent in patients 61 to 90 years old. Forty-five patients (14.2%; 95%CI: 10.4-18.0) were referred to a specialist immediately and an additional 34 (10.7%; 95%CI: 7.3-14.1) by one month follow-up. Fourteen patients (4.4%) were hospitalized immediately, and 11 (3.5%) within one month. Six patients (1.9%), all 61 to 90 years old, died within one month. CONCLUSION: Dyspnoea occurs in about two per cent of consultations. Serious cases are rare and are much more likely in the older age group. Twenty five per cent of the contacts concerning acute or worsening dyspnoea were referred to a specialist or hospitalized. In daily practice, the risk of immediate referral, hospitalization and death is higher in men and older patients, especially if the contact is at the patient's home. [Box: see text]. PMID- 27652901 TI - Current views of pediatric B Cell Precursor Acute Leucoyteic Leukemia: a review. AB - The most common type cancer prevailing in pediatric patients worldwide is acute lymphoblastic leukemia (ALL). The characteristic feature of this cancer is the accumulation of immature lymphoid cell in the bone marrow. Further a subtype of ALL namely B-cell precursor (BCP) ALL has raised in the recent years and is the most common subtype of ALL prevalent in children worldwide. The present review article will put light on the current aspects of BCP ALL including etiology, causative factors, diagnostic and treatment. PMID- 27652900 TI - Pediatric cardiovascular risk factors. AB - The dominant cause of mortality, morbidity and hospitalization worldwide is cardiac complications, and are the major public health problem in adult populations. The worldwide research is being focused on the idea that cardiovascular disease is an early life pathological state. Early unfavorable exposures, acting in different periods of fetal and early postnatal life, have been observed to be responsible for permanent editions in the cardiac system. This idea has been confirmed by preclinical experimental studies confirming the early life growth restriction leading to developmental adaptations in cardiovascular form and system. All these editions results in elevated susceptibility to cardiovascular disease. The present review article will put emphasis on these risk factors, which lead to the deadly cardiac pathology state in young infants. PMID- 27652902 TI - Antiretroviral therapy in HIV affected children: a review. AB - The pediatric Highly Active Antiretroviral Therapy (HAART) has shown enormous progress in recent years but still, a high percentage of children continue to experience treatment failure. The main causes found responsible are the development of drug resistance, inadequate dosing and poor adherence. This review is aimed at exploring the current status of antiretroviral therapy in children with focus on the interaction between disease, drug and patient behavior, all of which are strongly correlated .An overview of HIV viral characteristics and of the available antiretroviral drug classes currently combined to avoid development of resistance has been also discussed. PMID- 27652903 TI - A Sensitive Triple Quadrupole Liquid Chromatography Mass Spectrometric Method for the Estimation of Valproic Acid in K2EDTA Human Plasma using Furosemide as the Internal Standard. AB - A valproic acid is primarily being used in the treatment of epilepsy is a histone deacetylase inhibitor and it is under investigation for treatment of HIV and various cancer indications. A specific, sensitive and fast bioanalytical LC-MS/MS method was developed with furosemide as an internal standard (IS) and thoroughly validated for the quantitation of valproic acid using turbo ion spray in negative ion mode. The analyte and IS was extracted using protein precipitation. The chromatographic separation of analytes from extracted matrix was achieved using a Chromolith RP 18e (2.0*50 mm) column with a gradient mobile phase comprising of acetonitrile and purified water with acetic acid. The elution of both peaks was achieved within 5.2 min, with retention times of 2.55 min and 1.67 min for valproic acid and IS, respectively. Quantitation of valproic acid was achieved by the pseudo SRM transition pairs (m/z 142.8->m/z 142.8), and SRM transition pair (m/z 328.8 ->m/z 204.6) for internal standard.The calibration standards of valproic acid showed linear over a range from 50 to 40 000 ng/mL, with a lower limit of quantitation of 50 ng/mL with accuracy of 3.74% and precision of 5.06%. The bias for inter- and intra-batch assays was 1.24-6.14% and 3.85-11.84%, respectively; while the corresponding precision was 2.56-16.37% and 1.29-11.34%, respectively. The developed method was used to monitor valproic acid levels in clinical samples. Because of higher sensitivity, this method can be used for therapeutic drug monitoring in pediatric subjects. PMID- 27652905 TI - Biomimetic Multi-Functional Superamphiphobic FOTS-TiO2 Particles beyond Lotus Leaf. AB - It is widely known that natural examples like lotus leaves can only repel room temperature water but cannot repel hot water and oils. Even though superamphiphobic surfaces composed of re-entrant "mushroom-like" or "T-shaped" structures are promising, they are generally regarded as substrate-dependent and difficult to fabricate, and hence, their practical use on various materials has been limited. Here, we synthesize a flower-like superamphiphobic FOTS-TiO2 powder by solvothermal process and self-assembly functionalization. These structured and functionalized submicron particles can repel the liquids with surface tension as low as 23.8 mN.m-1 (n-decane), which is the lowest among powder samples. With respect to the biomimetic aspect, the surface morphology of FOTS-TiO2 particle is similar to the hierarchical micro/nano-structures of the lotus leaf surface, but it is beyond the lotus leaf for superoleophobic capacity. The difference in the oleophobicity is suggested to be the interplay of quasi-spherical re-entrant structure and perfluorined modification. Because of superior superamphiphobicity of the powder, a facile yet versatile strategy is developed, adhesive-assisted sieve deposition fabrication (AASDF), for preparing superamphiphobic coatings on various substrates. The investigation results pertaining to the water/oil proofing, mechanical durability, self-cleaning, and antifouling performances prove that the FOTS-TiO2 coating is robust and multifunctional, which will enable more opportunities for practical applications. Apart from these general applications, we find that the superamphiphobic FOTS-TiO2 powders when coated on sponge as anti-icing surface have good ice delay and icephobic performances. Furthermore, they can be used to prepare magnetic Fe3O4&FOTS-TiO2 composite particles through liquid marbles, implying significant scientific value. PMID- 27652904 TI - Inference of gene regulation functions from dynamic transcriptome data. AB - To quantify gene regulation, a function is required that relates transcription factor binding to DNA (input) to the rate of mRNA synthesis from a target gene (output). Such a 'gene regulation function' (GRF) generally cannot be measured because the experimental titration of inputs and simultaneous readout of outputs is difficult. Here we show that GRFs may instead be inferred from natural changes in cellular gene expression, as exemplified for the cell cycle in the yeast S. cerevisiae. We develop this inference approach based on a time series of mRNA synthesis rates from a synchronized population of cells observed over three cell cycles. We first estimate the functional form of how input transcription factors determine mRNA output and then derive GRFs for target genes in the CLB2 gene cluster that are expressed during G2/M phase. Systematic analysis of additional GRFs suggests a network architecture that rationalizes transcriptional cell cycle oscillations. We find that a transcription factor network alone can produce oscillations in mRNA expression, but that additional input from cyclin oscillations is required to arrive at the native behaviour of the cell cycle oscillator. PMID- 27652906 TI - Developing a Modern Approach To Account for Steric Effects in Hammett-Type Correlations. AB - The effects of aryl ring ortho-, meta-, and para-substitution on site selectivity and enantioselectivity were investigated in the following reactions: (1) enantioselective Pd-catalyzed redox-relay Heck reaction of arylboronic acids, (2) Pd-catalyzed beta-aryl elimination of triarylmethanols, and (3) benzoylformate decarboxylase-catalyzed enantioselective benzoin condensation of benzaldehydes. Through these studies, it is demonstrated that the electronic and steric effects of various substituents on selectivities obtained in these reactions can be described by NBO charges, the IR carbonyl stretching frequency, and Sterimol values of various substituted benzoic acids. An extended compilation of NBO charges and IR carbonyl stretching frequencies of various substituted benzoic acids was used as an alternative to Hammett values. These parameters provide a correlative tool that allows for the analysis of a much greater range of substituent effects because they can also account for proximal and remote steric effects. PMID- 27652907 TI - Optical Rotation Calculations for Fluorinated Alcohols, Amines, Amides, and Esters. AB - We have calculated the optical rotation at lambda = 589 nm for 45 fluorinated alcohols, amines, amides, and esters using both time-dependent density functional theory (TDDFT) with the CAM-B3LYP functional and the second-order approximate coupled-cluster singles and doubles (CC2) method, where the aug-cc-pVDZ basis set was adopted in both methods. Comparison of CAM-B3LYP and CC2 results to experiments illustrates that both methods are able to reproduce the experimental optical rotation results for both sign and magnitude. Several conformers for molecules containing the benzyloxy and naphthalene groups needed to be considered to obtain consistent signs with experiments, and these conformers are discussed in detail. We have also used a two-point inverse power extrapolation of the basis set to investigate the optical rotation in the basis set limit at the CC2 level, however, we only found small differences compared to the aug-cc-pVTZ results. Our results demonstrate that the least computationally expensive method investigated here, the CAM-B3LYP functional with the aug-cc-pVDZ basis set, is a reliable method to predict the optical rotation for large molecules and thereby the absolute configuration of chiral molecules. PMID- 27652908 TI - Computer decision support for acute kidney injury: current and future. AB - PURPOSE OF REVIEW: Growing awareness regarding the impact of acute kidney injury (AKI) as a grave consequence of critical illnesses resulted in the expansion of the need for early detection and appropriate management strategies. Clinical decision support systems (CDSS) can generate information to improve the care of AKI patients by providing point-of-care accurate patient-specific information and recommendations. Our objective is to describe the characteristics of CDSS and review the current knowledge regarding the impact of CDSS on patients in the acute care settings, and specifically for AKI. RECENT FINDINGS: Several recent systematic analyses showed the positive impact of CDSS on critically ill patients care processes. These studies also highlighted the scarcity of data regarding the effect of CDSS on the patient outcomes. In the field of AKI, there have been several reports to describe development and validation of homegrown CDSS and electronic alert systems. A large number of investigations showed the implementation of CDSS could improve the quality of AKI care; although, only in a very small subgroup of these studies patient outcomes improved. SUMMARY: The heterogeneity of these studies in their size, design, and conduct has produced controversial findings; hence, this has left the field completely open for further investigations. PMID- 27652909 TI - Cracking of Polycrystalline Graphene on Copper under Tension. AB - Roll-to-roll manufacturing of graphene is attractive because of its compatibility with flexible substrates and its promise of high-speed production. Several prototype roll-to-roll systems have been demonstrated, which produce large-scale graphene on polymer films for transparent conducting film applications.1-4 In spite of such progress, the quality of graphene may be influenced by the tensile forces that are applied during roll-to-roll transfer. To address this issue, we conducted in situ tensile experiments on copper foil coated with graphene grown by chemical vapor deposition, which were carried out in a scanning electron microscope. Channel cracks, which were perpendicular to the loading direction, initiated over the entire graphene monolayer at applied tensile strain levels that were about twice the yield strain of the (annealed) copper. The spacing between the channel cracks decreased with increasing applied strain, and new graphene wrinkles that were parallel to the loading direction appeared. These morphological features were confirmed in more detail by atomic force microscopy. Raman spectroscopy was used to determine the strain in the graphene, which was related to the degradation of the graphene/copper interface. The experimental data allowed the fracture toughness of graphene and interfacial properties of the graphene/copper interface to be extracted based on classical channel crack and shear-lag models. This study not only deepens our understanding of the mechanical and interfacial behavior of graphene on copper but also provides guidelines for the design of roll-to-roll processes for the dry transfer of graphene. PMID- 27652910 TI - Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure. AB - BACKGROUND: Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertrophy and failure. METHODS: Wistar rats were subjected to pulmonary trunk banding to induce compensated RV hypertrophy (n = 32) or manifest RV failure (n = 32). Rats without banding served as healthy controls (n = 30). The hearts were excised and perfused in a Langendorff system and subjected to iloprost, treprostinil, epoprostenol, or MRE-269 in increasing concentrations. The effect on RV function was evaluated using a balloon-tipped catheter inserted into the right ventricle. RESULTS: In control hearts, iloprost, treprostinil, and MRE-269 improved RV function. The effect was, however, absent in hearts with RV hypertrophy and failure. Treprostinil and MRE-269 even impaired RV function in hearts with manifest RV failure. CONCLUSIONS: Iloprost, treprostinil, and MRE-269 improved RV function in the healthy rat heart. RV hypertrophy abolished the positive inotropic effect, and in the failing right ventricle, MRE-269 and treprostinil impaired RV function. This may be related to changes in prostanoid receptor expression and reduced coronary flow reserve in the hypertrophic and failing right ventricle. PMID- 27652911 TI - Dexmedetomidine Depresses Sinoatrial and Atrioventricular Nodal Function Without Any Change in Atrial Fibrillation Inducibility. AB - It has been reported that dexmedetomidine (dex) has an impact on the cardiac conduction system and even has potential antiarrhythmic actions. We examined the influence of dex on the cardiac electrophysiological properties and atrial fibrillation (AF) inducibility. Adult paroxysmal AF patients were randomly assigned to receive (N = 107) or not receive (N = 108) dex during cardiac electrophysiological studies. The corrected sinus node recovery time (558 +/- 331 vs. 459 +/- 260 milliseconds; P = 0.02), Wenckebach cycle length (P < 0.001), atrioventricular nodal effective refractory period (317 +/- 76 vs. 252 +/- 54 milliseconds; P < 0.001), and atrio-His interval (P < 0.001) were longer in patients with dex than in those without. We tested the induction of repetitive atrial firing (RFA) defined as the occurrence of >=2 successive atrial activities induced by single premature atrial stimuli to determine the AF inducibility. RFA was seen with a similar proportion (41.1% vs. 44.4%), yet it was evoked at a longer stimulus coupling interval in the dex patients, which was potentially attributed to the longer atrial effective refractory period (237 +/- 36 vs. 213 +/- 27 milliseconds; P < 0.001) and more prolonged atrial conduction delay seen in the dex group. In conclusion, dex may depress the sinus and atrioventricular nodal function, however, it may not reduce the AF inducibility. PMID- 27652912 TI - HORIZONTAL RIDGE AS A POSTERIOR POLE FINDING IN A HIGHLY MYOPIC EYE WITH DOME SHAPED MACULA. AB - PURPOSE: This article describes a case with a highly myopic eye and a posterior pole with ridge-like lesions. METHODS: Case report. RESULTS: A 72-year-old man with unilateral high myopia showed poor vision and an extremely elongated axial length in his right eye, but normal vision and normal axial length in his left eye. He was examined using fundus examination and optical coherence tomography, and revealed to have dome-shaped macula with two horizontal ridges connecting the optic disc and the macula in his highly-myopic eye. CONCLUSION: The findings suggest that a dome-shaped macula may not be limited to the macula area, but may involve the whole posterior pole and is potentially involved in the elongation of highly myopic eyeballs. PMID- 27652914 TI - RISK FACTORS FOR DEVELOPMENT OF MACULAR HOLE RETINAL DETACHMENT AFTER PARS PLANA VITRECTOMY FOR PATHOLOGIC MYOPIC FOVEOSCHISIS. AB - PURPOSE: To identify the risk factors for the development of macular hole retinal detachment (MHRD) after vitrectomy without internal limiting membrane peeling for pathologic MF. METHODS: We retrospectively reviewed the records of 131 eyes (115 patients) treated with vitrectomy for pathologic MF from 2009 to 2014. The best corrected visual acuity (BCVA), refractive error, axial length, and spectral domain optical coherence tomography findings were analyzed. RESULTS: Postoperative MHRD developed in 7 eyes (5.3%). Between patients with or without secondary MHRD after vitrectomy, there were no significant differences in age, sex, axial length, preoperative BCVA, refractive error, lens status, and presence of posterior staphyloma. Spectral-domain optical coherence tomography showed all 7 eyes (100%) had foveal detachment, while only 47 patients (37.9%) of 124 eyes had foveal detachment (P = 0.004). There was no significant difference between preoperative and postoperative BCVA in the 7 eyes with MHRD. The postoperative BCVA in the 124 eyes without MHRD was significantly improved (P < 0.001). Among the 124 eyes, both preoperative and postoperative BCVA of eyes with foveal detachment was worse than the eyes without foveal detachment (P < 0.001, respectively). CONCLUSION: Preoperative foveal detachment is a risk factor for the development of MHRD after vitrectomy for pathologic MF. PMID- 27652915 TI - INTRAVITREAL AFLIBERCEPT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH LIMITED RESPONSE TO RANIBIZUMAB: A Treat-and-Extend Trial. AB - PURPOSE: To evaluate aflibercept treat-and-extend regimen for treatment of neovascular age-related macular degeneration in patients with limited response to ranibizumab. METHODS: This prospective single-arm trial included 33 patients with neovascular age-related macular degeneration pretreated with treat-and-extend regimen ranibizumab for >=6 months who failed to be extended to a 6-week interval at least twice. All patients received aflibercept (2 mg/0.05 mL) at baseline, and were subsequently treated according to treat-and-extend regimen, starting with a 4-week interval and extending in 2-week steps. Evaluations included mean maximum recurrence-free treatment interval; best-corrected visual acuity; central retinal thickness; and pigment epithelium detachment height and horizontal diameter. RESULTS: At Week 24, the maximum recurrence-free treatment interval increased to >=6 weeks in ~35% of patients, whereas the mean interval was 4.9 +/- 1.3 weeks. Best-corrected visual acuity score remained stable, but significant reductions in central retinal thickness (P < 0.001) and pigment epithelium detachment height (P = 0.001) were observed compared with baseline, as was a small decrease in horizontal pigment epithelium detachment diameter (P = 0.035). CONCLUSION: After switching patients with limited ranibizumab response to aflibercept, signs of choroidal neovascularization activity regressed, and an increased duration of treatment effects was seen in approximately one-third of lesions, but visual acuity was unchanged. PMID- 27652913 TI - CLINICAL ENDPOINTS FOR THE STUDY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: To summarize the recent literature describing the application of modern technologies in the study of patients with geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: Review of the literature describing the terms and definitions used to describe GA, imaging modalities used to capture and measure GA, and the tests of visual function and functional deficits that occur in patients with GA. RESULTS: In this paper, we describe the evolution of the definitions used to describe GA. We compare imaging modalities used in the characterization of GA, report on the sensitivity and specificity of the techniques where data exist, and describe the correlations between these various modes of capturing the presence of GA. We review the functional tests that have been used in patients with GA, and critically examine their ability to detect and quantify visual deficits. CONCLUSION: Ophthalmologists and retina specialists now have a wide range of assessments available for the functional and anatomic characterization of GA in patients with age-related macular degeneration. To date, studies have been limited by their unimodal approach, and we recommend that future studies of GA use multimodal imaging. We also suggest strategies for the optimal functional testing of patients with GA. PMID- 27652916 TI - ELECTRORETINOGRAPHIC AND VISUAL-EVOKED POTENTIAL CHANGES IN RELATION TO CHELATION MODALITY IN CHILDREN WITH THALASSEMIA. AB - PURPOSE: To evaluate possible benefits of using electrophysiological investigations for detecting retinal and visual pathway changes and correlating them with chelation modality in children with thalassemia. METHODS: This study included 60 patients on single oral iron chelator (deferasirox) (Group 1), 60 on deferoxamine chelator (Group 2), and 60 controls (Group 3). Participants underwent full ophthalmologic examination, pattern visual-evoked potential, pattern electroretinogram, and multifocal electroretinogram. RESULTS: Fundus showed no abnormalities. Multifocal electroretinogram mean P1 amplitude showed statistically significant differences in all 5 rings, amplitudes being significantly lower in Groups 1 and 2 than Group 3; moreover, significantly lower in Group 2 than Group 1. There was a statistically significant difference between groups regarding P50 wave latency and N35-P50 of pattern electroretinogram amplitude (P < 0.001 and P < 0.001, respectively). However, there were no statistically significant differences between groups regarding N95 wave of pattern electroretinogram and pattern visual-evoked potential waves' amplitude and latency. Multiple regression analyses illustrated that chelator was the most important determinant for multifocal electroretinogram and P50 parameters. CONCLUSION: Preclinical electrophysiologic changes existed in thalassemics, more obvious in those on deferoxamine. Electrophysiologic studies analysis denotes an early toxic macular insult rather than optic nerve affection. Thus, regular follow-up using multifocal electroretinogram and pattern electroretinogram is recommended. PMID- 27652918 TI - Michael Addition-Lactonization of Arylacetyl Phosphonate to beta,gamma Unsaturated alpha-Keto Esters for the Synthesis of Chiral syn-3,4 Dihydropyranones and 5,6-Dihydropyranones. AB - Catalytic asymmetric Michael addition-lactonization of arylacetyl phosphonates to beta,gamma-unsaturated alpha-keto esters by a chiral bifunctional thiourea tertiary amine was established. Using the developed protocol, a range of optically pure syn-3,4-dihydropyranones were generated in good yields with good to excellent stereoselectivities (up to >20:1 dr and 99% ee). Meanwhile, when stoichiometric diisopropylethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene were used as the base for the same reaction, a series of 5,6-dihydropyranones could be obtained in moderate to good yields (53-75% yield). PMID- 27652919 TI - Isophthalate-Hydrazone 2D Zinc-Organic Framework: Crystal Structure, Selective Adsorption, and Tuning of Mechanochemical Synthetic Conditions. AB - A new layered mixed-linker metal-organic framework [Zn2(iso)2(pcih)2]n (MOF) built from isophthalate ions (iso2-) and 4-pyridinecarbaldehyde isonicotinoyl hydrazone (pcih) was prepared using both solution and mechanochemical methods. By use of the latter, the 2D MOF is obtained either in a one-mortar three-component grinding or on the way of a two-step mechanosynthesis. Tuning of mechanochemical synthetic conditions allowed us to identify both necessary and favorable factors for the solid-state formation of the MOF. Single-crystal X-ray diffraction reveals the presence of interdigitated layers in the ABAB arrangement and interlayer 0D cavities filled with guest molecules. Upon thermal activation, the dynamic framework exhibits stepwise and selective adsorption of CO2 over N2 as well as high-pressure H2 adsorption reaching maximum excess of 1.15 wt% at 77 K. The mechanochemical synthetic protocol is expanded to a few other interdigitated structures. PMID- 27652920 TI - Empirically derived cut-points for sedentary behaviour: are we sitting differently? AB - Sedentary behaviour (SB) is associated with a number of adverse health outcomes. Studies that have used ActiGraph monitors to define sedentary time tend to use a threshold of <100 counts per minute (cpm) for classifying SB; however, this cut point was not empirically derived for adults. It is not known whether ActiGraph cut-points for SB differ depending on the context in which it occurs. We aimed to: (1) empirically derive an optimal threshold for classifying SB, using the cpm output from the ActiGraph GT3X+, compared to the sedentary classification from the activPAL3TM; and (2) ascertain whether this varied by day of the week and in working time versus non-working time. A convenience sample of 30 office-based university employees (females (66.67%); age 40.47 +/- 10.95 years; BMI 23.93 +/- 2.46 kg m-2) wore the ActiGraph GT3X+ and activPAL3TM devices simultaneously for seven days. Data were downloaded in 1 min epochs and non-wear time was removed. Generalised estimating equations were used to make minute by minute comparisons of sedentary time from the two devices, using sedentary minutes (when all 60 s were classified as sitting/lying) from the activPAL3TM as the criterion measure. After data reduction participants provided on average 11 h 27 min of data per day. The derived cut-points from the models were significantly higher on a Saturday (97 cpm) compared to weekdays (60 cpm) and Sunday (57 cpm). Derived cpm for sedentary time during working time were significantly lower compared to non-working time (35 (95%CI 30-41) versus 73 (54-113)). Compared to the 100 cpm and 150 cpm thresholds, the empirically derived cut-points were not significantly different in terms of area-under-the-curve, but had lower mean bias for working and non-working times. Accelerometer cut-points for SB can depend on day and also domain, suggesting that the nature of sitting differs depending on the context in which sedentary time is accrued. PMID- 27652921 TI - Nasopharyngeal dimensions in normal individuals: normative data. AB - OBJECTIVE: To establish normative values of minimum cross-sectional nasopharyngeal area in individuals without craniofacial anomalies at different age ranges. MATERIAL AND METHOD: Ninety-six individuals of both genders, without craniofacial anomalies, and with normal body mass index and neck circumference were evaluated. Participants were divided into 4 age groups: children, aged 6 to 10 years (G1); adolescents, aged 11 to 17 years (G2); young adults, 18 to 39 years (G3), and middle-aged adults, 40 to 59 years (G4). Minimum cross-sectional nasopharyngeal area (nasopharyngeal area - NPA) was assessed by means of modified anterior rhinomanometry (pressure-flow technique) using a PERCI-SARS system (version 3.50 - Microtronics Corp.). RESULTS: Mean+/-SD values of NPA were 1.025+/-0.054cm2, 1.055+/-0.081cm2, 1.050+/-0.083cm2, and 1.054+/-0.081cm2, respectively for groups G1, G2, G3, and G4, showing that there were no differences between the four age groups. CONCLUSION: Normative data of NPA were established for individuals without craniofacial anomalies from different age ranges, and they may be used as reference values in the clinical routine and for future studies regarding nasopharyngeal obstruction diagnosis, particularly in cases of craniofacial anomalies. PMID- 27652922 TI - Editorial. PMID- 27652923 TI - Variables in P300 recording: task type and electrode position. AB - PURPOSE: To analyze the latency and amplitude of P300 responses obtained with electrodes positioned at Cz and Fz and in different tasks of infrequent stimulus identification in normal hearing individuals. METHODS: Forty adults of both genders participated in the study. Three recordings with three different tasks were obtained for the identification of the infrequent stimulus; simultaneous recordings were obtained from Cz and Fz positions. RESULTS: Cz position showed significantly greater amplitudes and lower latencies than Fz. Regarding the three tasks, only "pronouncing the word 'thin'" was different from "raising a finger", with lowest latencies for the verbal task. Regarding amplitude, significantly higher values were observed for "raising a finger", followed by "pronouncing the word 'thin'" and mental counting. CONCLUSION: Cz obtained the best values, highest amplitude and lowest latency. Lowest latencies were obtained for the task of "pronouncing the word 'thin'" and the highest amplitudes were obtained for "raising a finger". PMID- 27652924 TI - Nouns and verbs used by preschoolers with language impairment. AB - PURPOSE: To compare the functional use of verbs and nouns by Brazilian Portuguese speaking children with language impairment (LI) and to verify whether their use of these word classes is different from that of children with typical language development (TLD). This study also aimed to compare the use of each verb type between groups. METHODS: Participants were 80 preschool children, 20 of them diagnosed with LI and 60 with TLD. The age ranges of participants were 3 to 6 years for children with LI and 2 to 4 years for children with TLD. Individuals were paired based on their expressive language age. Ludic interaction was used to elicit the speech sample from which nouns and verbs were selected from spontaneous speech. All nouns and verbs were tabulated and verbs were classified. RESULTS: Preschoolers with LI use verbs more often than nouns in their production of spontaneous speech. The use of nouns presented no difference between the groups, but verb use frequency was higher in children with LI for the 3-year-old subgroup. The verbs most frequently used by children with LI were copula, intransitive, and transitive direct. Comparison between the groups revealed few differences regarding the use of transitive direct, bitransitive, and copular verbs. Only transitive circumstantial verbs were more often used by children with TLD at all ages. CONCLUSION: The use of nouns and verbs by children with LI complies with the typical development standard, but it occurs more slowly. The use of verbs with fewer complements is predominant in these children. PMID- 27652925 TI - Impact of specific language impairment and type of school on different language subsystems. AB - PURPOSE: This study aimed to explore quantitative and qualitative effects of type of school and specific language impairment (SLI) on different language abilities. METHODS: 204 Brazilian children aged from 4 to 6 years old participated in the study. Children were selected to form three groups: 1) 63 typically developing children studying in private schools (TDPri); 2) 102 typically developing children studying in state schools (TDSta); and 39 children with SLI studying in state schools (SLISta). All individuals were assessed regarding expressive vocabulary, number morphology and morphosyntactic comprehension. RESULTS: All language subsystems were vulnerable to both environmental (type of school) and biological (SLI) effects. The relationship between the three language measures was exactly the same to all groups: vocabulary growth correlated with age and with the development of morphological abilities and morphosyntactic comprehension. Children with SLI showed atypical errors in the comprehension test at the age of 4, but presented a pattern of errors that gradually resembled typical development. CONCLUSION: The effect of type of school was marked by quantitative differences, while the effect of SLI was characterised by both quantitative and qualitative differences. PMID- 27652926 TI - Work process, performance and professional profile of a Hearing Health Network: reference for satisfaction. AB - PURPOSE: To analyze the correlation between the satisfaction of professionals from the Hearing Health Care network in two micro-regions of Minas Gerais state and the sociodemographic profile, work process, and work performance in the health service. METHODS: This is a cross-sectional, observational, analytic study with a non-probabilistic sample including 34 professionals from the Hearing Health Care services. Data collection occurred through individual interviews in the municipality of professional practice. Associations between the Professional Satisfaction variable and the explanatory variables Sociodemographic Data, Work Routine, and Developed Actions were conducted. RESULTS: Professionals with graduate studies were more satisfied with the human resources policy and the activities developed, whereas health civil servants showed more satisfaction with the wage policy and the work schedule. The correlation analysis between work process and satisfaction revealed a moderate positive correlation between items such as Health Promotion Actions, Satisfaction with Diagnostic Equipment, and Satisfaction with Maintenance Equipment. CONCLUSION: The present study revealed a higher level of satisfaction among professionals with graduate studies (human resources policy and activities developed) and civil servants (wage policy and work schedule). The relevance of this study lies on the important role that health professionals play on the Health Care Network. Additionally, the study of satisfaction level can provide a search for improvements, considering that satisfied professionals not only improve service quality, but also show greater creativity, commitment, and performance. PMID- 27652927 TI - Aspects of the speaking voice of elderly women with choral singing experience. AB - INTRODUCTION: Despite several studies related to singing and aging voice found in the literature, there is still the need for investigation seeking to understand the effects of this practice in the speaking voice of the elderly. OBJECTIVE: To compare the characteristics of the speaking voice of elderlies with experience in choral singing with those of elderlies without this experience. METHOD: Participants were 75 elderly women: 50 with experience in choral singing - group of singers (SG) and 25 without experience - group of nonsingers (NSG). A questionnaire was applied to characterize the elderly and collect data with respect to lifestyle and voice. Speech samples (sustained vowels, repetition of sentences, and running speech excerpts) were collected in a quiet room in sitting position. The voices were analyzed by three expert speech-language pathologists according to the protocol Consensus Auditory-Perceptual Evaluation of Voice (CAPE V). Data were submitted to descriptive and statistical analysis. RESULTS: The voices of elderly nonsingers (NSG) showed significant increase in scores related to the overall degree of deviance and presence of roughness and strain. CONCLUSION: Analysis of the aspects of the speaking voice of subjects in the SG, compared with that of subjects in the NSG, showed better overall degree of deviance due to lower roughness and strain. PMID- 27652928 TI - Voice care knowledge by dysphonic and healthy individuals of different generations. AB - The purpose of this study was to identify the opinions of both dysphonic and vocally healthy individuals regarding the factors that affect their voices positively and negatively, analyzing them according to the generation to which the participants belong. Eight hundred sixty-six individuals (304 dysphonic and 562 vocally healthy; 196 men and 670 women) categorized by generation: 22 individuals in Silent Generation (1926/-/1945), 180 in Baby Boomers (1946/ /1964), 285 in Generation X (1965/-/1981), and 379 in Generation Y (1982/-/2003) responded to two open questions: "Cite five things that you believe are good/bad to your voice". Five thousand, two hundred sixty answers were identified (2478 positive and 2782 negative) and organized in 365 factors related to voice care. The three most prevalent positive and negative factors for each generation were as follows: Silent Generation - positive factors: 1 - water, honey and pomegranate, 2 - apple, and 3 - ginger tea, voice exercises and gargling; negative factors: 1 - cold drinks, 2 - excessive speaking, and 3 - alcoholic drinks, smoking and screaming; Baby Boomers - positive factors: 1 - water, 2 - apple, and 3 - sleeping well; negative factors: 1 - cold drinks, 2 - screaming, and 3 - smoking; Generation X - positive factors: 1 - water, 2 - apple, and 3 - vocal warm-up; negative factors: 1 - screaming, 2 - smoking, and 3 - alcoholic drinks; and Generation Y - positive factors: 1 - water, 2 - apple, and 3 - vocal warm-up; negative factors: 1 - screaming, 2 - smoking, and 3 - alcoholic drinks. The impact of generation was greater on the frequency of the responses than on their type. Water and apple were the most frequently cited positive factors for all the generations investigated, whereas screaming and smoking were the most frequently mentioned negative factors. Behavioral aspects related to popular beliefs were reported more frequently by the older generations. PMID- 27652929 TI - Language development and its relation to social behavior and family and school environments: a systematic review. AB - PURPOSE: To conduct a systematic review of the literature on the relationship between language development, social behavior, and family and school environments in children aged 4 to 6 years. RESEARCH STRATEGY: Papers published between March 2009 and March 2014 were searched in electronic databases. The first phase of the study consisted in preparing the guiding question. Subsequently, survey and selection of studies were conducted. To this end, descriptors were defined by groups of themes. SELECTION CRITERIA: The following types of publications were included in the search: complete scientific articles available in full and freely and original research papers or literature reviews published in the past five years covering the 4 to 6-year age range. DATA ANALYSIS: The analysis of the papers was conducted through critical reading and selection of the results that responded to the guiding question. RESULTS: Fourteen articles were selected. Most of the studies used at least one standardized instrument. Research indicates that the family environment is related to language development, mainly regarding socioeconomic status and parental education; number of adults who live with the child; parental health; language motivation; and interaction between parents and children. Only one article showed association between quality of the school environment and language development, and none showed evidence of an association between social behavior and language development. CONCLUSION: Most of the studies analyzed focus on the relationship between family environment and language development. Very few studies with this approach are available in the specific literature. PMID- 27652930 TI - Is targeted therapy possible for patients with gastric adenocarcinoma? PMID- 27652931 TI - Mesenchymal Stem/Stromal Cells seeded on cartilaginous endplates promote Intervertebral Disc Regeneration through Extracellular Matrix Remodeling. AB - Intervertebral disc (IVD) degeneration is characterized by significant biochemical and histomorphological alterations, such as loss of extracellular matrix (ECM) integrity, by abnormal synthesis of ECM main components, resultant from altered anabolic/catabolic cell activities and cell death. Mesenchymal Stem/Stromal Cell (MSC) migration towards degenerated IVD may represent a viable strategy to promote tissue repair/regeneration. Here, human MSCs (hMSCs) were seeded on top of cartilaginous endplates (CEP) of nucleotomized IVDs of bovine origin and cultured ex vivo up to 3 weeks. hMSCs migrated from CEP towards the lesion area and significantly increased expression of collagen type II and aggrecan in IVD, namely in the nucleus pulposus. Concomitantly, hMSCs stimulated the production of growth factors, promoters of ECM synthesis, such as fibroblast growth factor 6 (FGF-6) and 7 (FGF-7), platelet-derived growth factor receptor (PDGF-R), granulocyte-macrophage colony-stimulating factor (GM-CSF) and insulin like growth factor 1 receptor (IGF-1sR). Overall, our results demonstrate that CEP can be an alternative route to MSC-based therapies for IVD regeneration through ECM remodeling, thus opening new perspectives on endogenous repair capacity through MSC recruitment. PMID- 27652933 TI - Editorial. AB - the family of nursing is worldwide. That's because people's need for nursing is basic and universal, and because, like the best families, its members are bound together by common values and shared knowledge. Our regular family gathering' in the form of the Quadrennial Congress of the International Council of Nurses takes place this year in Madrid - the first time for 25 years that it has been held in Europe. PMID- 27652932 TI - A Wound Closed: A Memoir. PMID- 27652934 TI - Behind closed doors. AB - With the unemployment total reaching three million last week, nurses are going to have to learn to compete in the job market. But to do so they need good career advice and training to equip them for the search for employment. PMID- 27652935 TI - Global unity. AB - the headquarters of the International Council of Nurses in Geneva, Switzerland, is part of a new building near the lake. There are 17 staff members and only four of us are nurses, yet we have a pretty productive team. PMID- 27652937 TI - Growing evidence of cuts in services and nursing posts. AB - * People who are out of work are more likely to become ill, be depressed and to commit suicide, according to a Liberal Democrats' report which coincided with the announcement that unemployment has topped three million in Britain. The Liberal Democrats have just completed a nationwide survey of the wider consequences for those without work. It found evidence of a disturbing link between early death and unemployment, with the death rate some 21 per cent above the national average. PMID- 27652936 TI - Mixed reaction to revised London hospital closure plan. AB - Nursing unions have given a mixed response to government plans for health services in London, which propose the closure of at least five hospitals in the capital and about 2,500 beds. PMID- 27652938 TI - Spotlight on congress. AB - With over 100 national nurses' associations in membership of the International Council of Nurses - of which the Royal College of Nursing is the largest - ICN Congress provides an unrivalled opportunity to meet with nurses from all over the world. It's a networker's paradise. PMID- 27652939 TI - Independent midwifery challenges medical myth. AB - Midwives who have left the 'safe' environment of the NHS to practise independently offer women choice, continuity and control, Royal College of Midwives General Secretary Ruth Ashton told a business seminar last week. It was 'sad' that the only way women could be assured of personalised, individual care during the antenatal, intrapartum and postnatal periods was to look outside the NHS, she said. Independent midwives 'have shown us what can be done'. PMID- 27652940 TI - Experiment reveals increased responsibility improves care. AB - An experimental project in which nurses perform tasks previously the preserve of junior doctors has improved patient care and saved money, a regional practice development manager claimed last week. But nurses' workloads have increased, especially at night, and doctors are reluctant to devolve decision-making resp onsibility, said Frances Pickers- gill of SE Thames RIIA. PMID- 27652941 TI - Little overlap with technicians' work. AB - There is little evidence of an overlap between nurses and technicians in high technology areas of care, according to a report commissioned by the Department of Health. PMID- 27652942 TI - Call to guarantee support for mentally disturbed offenders. AB - Funding for the support of mentally disturbed offenders must be ringfenced to ensure they receive adequate care after the shake-up of community services on April 1, the National Association for the Care and Resettlement of Offenders (Nacro) has warned. PMID- 27652944 TI - Congress highlights. AB - as ICN Executive Director Constance Holleran points out: Nurses from the UK have always been at the forefront of the work of ICN, starting with Ethel Bedford Fenwick in 1899. The Royal College of Nursing is the largest member of ICN and RCN President Dr June Clark is working with the ICN Professional Services Committee on the Classification of Nursing Practice project. Former RCN General Secretary Trevor Clay is first vice president and Robert Tiffany [formerly Chief Nurse at The Royal Marsden Hospital] is a member of the Board of Directors.' PMID- 27652943 TI - Scots satisfied with services. AB - A survey of NHS patients across Scotland has confirmed a high level of satisfaction with the services provided. PMID- 27652945 TI - The days of DHAs and FHSAs may be numbered. AB - The days of District Health Authorities and Family Health Service Authorities are numbered, the Audit Commission's David Browning told delegates. PMID- 27652946 TI - CNs need more responsibility to manage own workloads. AB - Community nurses need fewer managers and more responsibility to manage their own workloads, an RCN conference heard last week. PMID- 27652947 TI - 'Golden handshake' for RHA chief in financial scandal. AB - Health Secretary Virginia Bottomley has given a 'golden handshake' to a regional health chief who quit amid a series of financial scandals. PMID- 27652948 TI - Auxiliaries to perform routine nursing tasks? AB - Nursing auxiliaries could administer insulin and perform other tasks traditionally the preserve of qualified nurses under plans being considered in South East Kent, the RCN London conference heard last week. PMID- 27652949 TI - ? AB - Russia More than two in five hospitals have no hot water and 12 per cent have no water supply at all, according statistics published in Nezavisimaya Gazeta, a Russian daily paper. PMID- 27652951 TI - World news. AB - United States More than half of nurses in the Milwaukee area have been verbally abused by both doctors and patients, a survey has found. But getting them and other health workers to whistleblow on their abusers remains a problem, the American journal Health Wire reports. PMID- 27652952 TI - Viva espana. AB - Situated in the heart of Spain, its capital since 1606 and a cultural centre with more than 50 museums and art galleries, Madrid is the country's second largest industrial centre (Barcelona being the first). A university city, seat of a royal residence and see of an archbishop, it was also one of the first cities in Europe to boast a branch of that now ubiquitous hamburger house - McDonald's. PMID- 27652953 TI - Parliament. AB - MIS managers' wage bills have increased almost eight times as much as nurses' have during the past two years, according to figures comparing NHS wage costs since 1989. PMID- 27652955 TI - Only certified personnel can practise occupational health. AB - Nurses who call themselves 'occupational health nurses' but do not hold the Occupational Health Nursing Certificate (OHNC) are breaking the law, according to legal expert Gillian Howard. PMID- 27652954 TI - Nursing a Spanish ambition. AB - for most of us, Spain has traditionally been a holiday destination, a country of sun and beaches where we can lay aside our cares and just relax. Occasionally, as we pack our bags to come home, we may wonder what it would be like to live and work there. Then we head for the airport having decided that this would be about as realistic as expecting a holiday romance to last. PMID- 27652956 TI - OH nurses must promote their value. AB - The time is ripe for occupational health nurses to 'sell themselves' to employers, according to Dr Ewan Mac Donald, Senior Lecturer at Glasgow University. He cited the removal of Crown immunity, the introduction of the Control of Substances Hazardous to Health (COSHH) and new EC Directives among the changes that have increased the need for OH nurses. PMID- 27652958 TI - Jam tomorrow... AB - There was no surprise, of course. It was known since the Autumn Statement last year, when John Major wrote to Review Body (RB) Chair Michael Bett, saying I the RB's remit was to be altered 'for the coming year', that the pay award was to be imposed rather than negotiated. PMID- 27652957 TI - A better London? AB - In a blaze of publicity, the Government finally launched its proposals last week for the future of health care in London. A cure for the capital's ills, the Health Secretary called it. A very bad day for London, said Labour. PMID- 27652959 TI - Careers out of control? AB - The ENB's Resource and Careers Service is the only one of its kind available to nurses, midwives and health visitors seeking advice on courses and career development in England. The ENB states in its Applicant Handbook: 'This office can provide detailed information about pre-registration courses and opportunities for career development in England.' PMID- 27652960 TI - Getting back to work. AB - Unemployment and fear of unemployment are not traditional problems for nurses. Until recently there had always been too many jobs chasing too few nurses. But the climate has changed and unemployment is now a real fear for many. The traditional sources for job hunting, such as advertisements in professional journals, offer one source of reemployment possibilities, but by no means the only one. The Employment Service has a wide range of support services at its fingertips. PMID- 27652961 TI - A community nurse at heart. AB - Although the job finding initiatives outlined are available to all, in the Employment Service nurses have something of a 'secret weapon' - the Nursing Employment Service (NES). PMID- 27652962 TI - Life exists outside London's confines. AB - I am in full agreement with the Nurses workcampaign. If patient care and safety is not to become compromised, then the government must review its attitude to the nursing profession. PMID- 27652963 TI - Feeling of being kicked in the teeth. AB - As a 42 year old married woman, I recently qualified following three years on a Project 2000 course. Unfortunately, I am unemployed. PMID- 27652964 TI - The challenge of evaluating skills. AB - I am writing with reference to the report about a recently published research study undertaken within Somerset Health District, which indicated that district nurses may be failing to assess and reassess the needs of their physically disabled clients (Clinical News, January 20). community care requirements which take effect from April. PMID- 27652965 TI - ? AB - "She thinks all this new lifting equipment is a waste of money." PMID- 27652966 TI - Employing foreign nurses is outrageous. AB - I was enraged at the report that a hospital in Newcastle may have to recruit paediatric nurses overseas to fill vacancies ('Paediatric recruitment crisis', News, February 10). I understand that a number of hospitals nationwide have run on low numbers within the paediatric environment. PMID- 27652967 TI - A question of national recognition. AB - I was very interested to read that Virginia Bottomley had announced cash help from the NILS Management Executive for nurse managers who want to undertake a Master's degree course (News, February 3). PMID- 27652968 TI - Time to act on staffing cutbacks. AB - As a full-time auxiliary for over 20 years with the same health authority, I work with an efficient, hard-working and dedicated team of qualified nurses whose main aim is our clients' well-being. PMID- 27652970 TI - Points of view. AB - The Care Sector Consortium (CSC) is the Industry Lead Body responsible for developing the occupational standards which form the basis of National Vocational Qualifications (NVQs). Several thousand health care assistants and health care support workers are currently being assessed for NVQs. PMID- 27652969 TI - Are you in need of information? AB - A number of members of the RCN Rheumatology Forum are complaining that they are not receiving information from the Forum. As well as the usual problems such as changes of address, surnames or not quoting RCN numbers, some of our members were inadvertently deleted from our membership list. PMID- 27652971 TI - Microchips on shoulders. AB - The name's Health. Nat Health, digitised investigator into services rhat care. Computers are easy, it's only the people involved that make them impossible. Particularly the computer experts. They've sold health authorities so many lemons, they could teach Pete Deale how to run his fruit stall in Albert Square. PMID- 27652972 TI - Caring for Children in Hospital J Cleary Caring for Children in Hospital Scutari Press I74pp L14.50 1-871364-67-1. AB - Caring for Children in Hospital contains information that should be of interest to all paediatric nurses. It argues that parents may take over the responsibility for care of their children in hospital. If this view is accepted, it has great implications for paediatric practice. PMID- 27652974 TI - Case Studies in Law and Nursing Case Studies in Law and Nursing A P Young Chapman & Hall 259pp L14.95 0-412-44130-6. AB - Case Studies in Law and Nursing is not, in the author's words, 'a conventional book, more a learning pack'. With the growing recognition that nurses need a sound knowledge of the law as it affects them and their practice, the book will serve to take much of mystique, confusion and even tedium out of that learning. PMID- 27652973 TI - Economics of Health Care Financing Economics of Health Care Financing C Donaldson et al . Macmillan Press 218pp L14.99 0-333-53870-6 [Formula: see text]. AB - Economics of Health Care Financing will be of interest to nurses undertaking a DMS or MBA, and to those who are interested in an international perspective on different ways of financing health care, and the continuing debate regarding the moral dilemmas of both consumers and providers of health care. PMID- 27652975 TI - ? PMID- 27652976 TI - Graphene as a Reversible and Spectrally Selective Fluorescence Quencher. AB - We report reversible and spectrally selective fluorescence quenching of quantum dots (QDs) placed in close proximity to graphene. Controlling interband electronic transitions of graphene via electrostatic gating greatly modifies the fluorescence lifetime and intensity of nearby QDs via blocking of the nonradiative energy transfer between QDs and graphene. Using ionic liquid (IL) based electrolyte gating, we are able to control Fermi energy of graphene in the order of 1 eV, which yields electrically controllable fluorescence quenching of QDs in the visible spectrum. Indeed, our technique enables us to perform voltage controllable spectral selectivity among quantum dots at different emission wavelengths. We anticipate that our technique will provide tunable light-matter interaction and energy transfer that could yield hybrid QDs-graphene based optoelectronic devices with novel functionalities, and additionally, may be useful as a spectroscopic ruler, for example, in bioimaging and biomolecular sensing. We propose that graphene can be used as an electrically tunable and wavelength selective fluorescence quencher. PMID- 27652977 TI - Predictive value of DCE-MRI for early evaluation of pathological complete response to neoadjuvant chemotherapy in resectable primary breast cancer: A single-center prospective study. AB - OBJECTIVE: This study proposed to establish a predictive model using dynamic enhanced MRI multi-parameters for early predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: In this prospective cohort study, 170 breast cancer patients treated with NAC were enrolled and were randomly grouped into training sample (136 patients) and validation sample (34 patients). DCE-MRI parameters achieved at the end of the first cycle of NAC were screened to establish the predictive model by using multivariate logistic regression model according to pCR status. Receiver operating characteristic curves were conducted to assess the predictive capability. The association between MRI-predicted pCR and actual pCR in survival outcomes was estimated by using the Kaplan-Meier method with log-rank test. RESULTS: Multivariate analysis showed DeltaAreamax and DeltaSlopemax were independent predictors for pCR, odds ratio were 0.939 (95%CI, 0.915 to 0.964), and 0.966 (95%CI, 0.947 to 0.986), respectively. A predictive model was established using training sample as "Y = -0.063*DeltaAreamax - 0.034*DeltaSlopemax", a cut-off point of 3.0 was determined. The AUC for training and validation sample were 0.931 (95%CI, 0.890-0.971) and 0.971 (95%CI, 0.923 1.000), respectively. MRI-predicted pCR patients showed similar RFS (p = 0.347), DDFS (p = 0.25) and OS (p = 0.423) with pCR patients. CONCLUSION: The multi parameter MRI model can be potentially used for early prediction of pCR status at the end of the first NAC cycle, which might allow timely regimen refinement before definitive surgical treatment. PMID- 27652978 TI - Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson's Disease. AB - Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in substantia nigra pars compacta, alpha-synuclein (alpha-syn)-rich intraneuronal inclusions (Lewy bodies), and microglial activation. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is dopaminergic substitution therapy and dopamine is an established transmitter connecting nervous and immune systems, we examined CD4+ T naive and memory lymphocytes in PD patients and in healthy subjects (HS), with specific regard to dopaminergic receptor (DR) expression. In addition, the in vitro effects of alpha-syn were assessed on CD4+ T naive and memory cells. Results showed extensive association between DR expression in T lymphocytes and motor dysfunction, as assessed by UPDRS Part III score. In total and CD4+ T naive cells expression of D1-like DR decrease, while in T memory cells D2-like DR increase with increasing score. In vitro, alpha-syn increased CD4+ T memory cells, possibly to a different extent in PD patients and in HS, and affected DR expression with cell subset-specific patterns. The present results support the involvement of peripheral adaptive immunity in PD, and may contribute to develop novel immunotherapies for PD, as well as to better use of current dopaminergic antiparkinson drugs. PMID- 27652979 TI - Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities. AB - Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug-drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to resistance treatment of viral infections. PMID- 27652980 TI - A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection. AB - We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and Colombia; data from a Thai population were retrieved from the literature. Across all cohorts, homozygosity for the short TIM-1 allele was more common in HESNs than in HIV-1 infected subjects. A meta-analysis of the four association analyses yielded a p value of 0.005. In vitro infection assays of CD4+ T lymphocytes indicated that homozygosity for the short allele is associated with lower rate of HIV-1 replication. These results suggest that the deletion allele protects from HIV-1 infection with a recessive effect. PMID- 27652982 TI - Pulmonary Manifestations of Acute Lung Injury: More Than Just Diffuse Alveolar Damage. AB - CONTEXT: - Acute pulmonary injury may occur as a result of myriad direct or indirect pulmonary insults, often resulting in hypoxemic respiratory failure and clinical acute respiratory distress syndrome. Histologically, most patients will exhibit diffuse alveolar damage on biopsy, but other histologic patterns may be encountered, such as acute eosinophilic pneumonia, acute fibrinous and organizing pneumonia, and diffuse alveolar hemorrhage with capillaritis. OBJECTIVE: - To review the diagnostic features of various histologic patterns associated with a clinical picture of acute lung injury, and to discuss key features in the differential diagnosis. DATA SOURCES: - The review is drawn from pertinent peer reviewed literature and the personal experience of the authors. CONCLUSIONS: - Acute pulmonary injury is a significant cause of morbidity and mortality. In addition to diffuse alveolar damage, pathologists should be aware of alternate histologic patterns of lung disease that may present with a similar clinical presentation because this may impact treatment decisions and disease outcome. PMID- 27652981 TI - Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936. AB - It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study. PMID- 27652983 TI - Outcomes of a conservative approach to management in amoebic liver abscess. AB - CONTEXT: Unfortunately, there is confusion among the medical community regarding the management of amoebic liver abscess (ALA). Therapeutic options range from simple pharmacotherapy to use of interventions like a needle or catheter aspiration under ultrasound guidance to surgical intervention. There is a plethora of thresholds for parameters such as the maximum diameter of the abscess and volume on ultrasound examination suggested by various authors to serve as a criterion to help to decide when to use which modality in these cases. AIMS: To assess the outcome of patients with uncomplicated ALA treated using a conservative approach. Moreover, to identify factors associated with its failure. SETTINGS AND DESIGN: A prospective, observational study was carried out at a large municipal urban health care center over a period of 3-year (2011-2014) in India. MATERIALS AND METHODS: Patients with uncomplicated ALA were recruited. All patients were managed with pharmacotherapy initially for a period of 72 h. Response to treatment was assessed by resolution of symptoms within the given time frame. Failure to respond was considered an indication for intervention. Needle aspiration was offered to these patients and response assessed within 72 h. Failure to respond to aspiration was considered an indication for catheter drainage. STATISTICAL ANALYSIS USED: Data recorded were entered in a Microsoft Office Excel Sheet and analyzed using the SPSS version 16.0 (IBM). RESULTS: Sixty patients with ALA were included in the study over its duration. Forty-nine (81.67%) patients were managed conservatively, while 11 (18.33%) patients needed an intervention for relief. Patients who required intervention had deranged liver function at presentation, a larger abscess diameter (10.09 +/- 2.23 vs. 6.33 +/- 1.69 cm P < 0.001) and volume (399.73 +/- 244.46 vs. 138.34 +/- 117.85 ml, P < 0.001) compared to those who did not need it. Patients that required intervention had a longer length of hospital stay (7.1 +/- 2.4 vs. 4.8 +/- 0.9 days, P < 0.001). On post hoc analysis, a maximum diameter of >7.7 cm was found to be the optimal criterion to predict the need of intervention in cases of ALA. CONCLUSIONS: A conservative approach is effective in the management of ALA for a majority of patients. Failure of conservative management was predicted by the size of the abscess (maximum diameter >7.7 cm). Even in the cases of failure, a gradual step-up with interventions was found to be safe and effective. PMID- 27652987 TI - Right atrial mural thrombi: An autopsy study of an under-diagnosed complication at an unusual site. AB - BACKGROUND: Right atrial mural thrombi (RAMT) are often seen in association with cardiac diseases or foreign bodies. Unusual locations at the flutter isthmus and the atrial appendage prompted us to evaluate our 2-year autopsy data on such thrombi. MATERIALS AND METHODS: In the 2-year retrospective autopsy, the clinical and autopsy records of patients with RAMT were reviewed, with particular reference to the presence of central venous catheter (CVC), its site of insertion, its type, material and size, its duration of placement, and the drugs infused through the catheter. RESULTS: Of the 940 autopsies performed in 2 years, RAMT was seen in 24 hearts and was related to an insertion of a CVC in 23 patients (95.8%). The risk and/or associated factors for this complication were tunneled and polyethylene catheters, Intensive Care Unit admission, infused drugs, underlying cardiac diseases, and pregnancy. A noteworthy feature was the location of the thrombi in the flutter isthmus in 16 hearts (66.7%) and atrial appendage in another six hearts. Localized endocarditis/myocarditis and pulmonary thromboembolism were observed in six and four patients, respectively. CONCLUSIONS: This autopsy study, which has a high incidence of catheter-related RAMT, does not reflect the true incidence but reiterates the importance of guided insertion of central venous and prompt recognition of thrombus formation. PMID- 27652991 TI - First Virtual Live Conference in Healthcare. AB - BACKGROUND: Conferences and meetings bring together thousands of doctors from diverse locations. However, the traveling, accommodation, and arrangement of venues for conferences and meetings are expensive and a lot of time needs to be devoted to these logistics. The purpose of this article was to present our own virtual live conference experience using web conferencing and to briefly outline the basics and advantages of this technology in organization of healthcare conferences. METHODS: Web conferencing technology was used to organize an international bariatric surgery conference, allowing a large number of attendees to participate and interact from wherever they were, using merely an Internet connection with a video player on their personal computers, laptops, or smartphones. RESULTS: A virtual live conference saves a lot of time and cost and simplifies the logistics needed to organize a learning conference with worldwide participation. CONCLUSION: As far as we know, this is the first report of a virtual live conference in healthcare. We see it as the future of organizing experts as well as medical teaching conferences. PMID- 27652986 TI - Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy. AB - The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future. PMID- 27652993 TI - Breastfeeding during the first year of life: estimates using records generated in general paediatrics. AB - INTRODUCTION: The monitoring of breastfeeding during a child's first year of life is highly recommended. The proportion of children who are exclusively breastfed for at least six months is a strong indicator of breastfeeding promotion in the community. The objectives of the study were to survey the exclusive breastfeeding of children during the first year of life for cohorts born in Trentino (north eastern Italy) in 2009 to 20013, evaluate the decrease of exclusive breastfeeding at six months and analyse possible relationships between the maintenance of breastfeeding up to the age of six months and certain maternal socio-demographic characteristics, as well as clinical aspects of the pregnancy and birth. EVIDENCE ACQUISITION: Cohorts born in Trentino between 2009 and 2013 were studied, calculating the proportion of infants who were breastfed upon discharge from the hospital (source: data on the CedAP informative flow, that is the Italian Certificate of Delivery Assistance data-base). The data provided on the 12-month health evaluation form found in the PEDIATRIC HEALTH BOOKLET, completed by regional family paediatricians, was linked with that of the respective CedAP (96.7% linkage). The trend for exclusive breastfeeding and its monthly decrease was analyzed. The maintenance of exclusive breastfeeding until the age of 6 months was analyzed in relation to citizenship, area of residence, maternal education level and employment status, parity, single or multiple birth, infant exposure to passive smoke and attendance or non-attendance of a state-promoted childbirth preparation course. This final variable was studied solely for primiparous women, who are generally most likely to attend a childbirth preparation course. All results were adjusted for the following potential confounding variables: "birth type", "prematurity" and "feeding method upon discharge from the hospital". EVIDENCE SYNTHESIS: CedAP data revealed that 83.5% of live infants were exclusively breastfed and that this percentage decreased to 34.7% by the age of 6 months (35.4% among full-term infants and 27% among premature infants). Data from the Province of Trento demonstrates that exclusive breastfeeding up to the age of 6 months is influenced by the mother's citizenship, area of residence and education level, but not by her employment status. In addition, the study revealed a significant association with parity, passive smoke exposure and attendance of a childbirth preparation course. CONCLUSIONS: The paediatric health booklet with its information on the state of health of children (in combination with data from the CedAP) offers a valid tool for monitoring breastfeeding during the first year of life. Data confirmed a decrease in the rate of breastfeeding between birth and the first month of life and between the first and sixth months of living at home. The results regarding the conditions that favour and discourage breastfeeding suggest potential public health care measures to improve children's health. PMID- 27652992 TI - Australia's evolving food practices: a risky mix of continuity and change. AB - OBJECTIVE: To investigate trends in five key aspects of Australian food practice which have been implicated in diet-related health risks, specifically energy intake. They are: the replacement of home-prepared foods by commercially prepared foods; consumer reliance on ultra-processed foods; de-structured dining; increased pace of eating; and a decline in commensal eating. DESIGN: Data were from repeated cross-sections from the national Household Expenditure and Time Use Surveys. Trends in food practice aspects were examined using indicators of food expenditure across different food groups and time spent eating and cooking, including where, when and with whom eating activities took place. SETTING: Australia, 1989-2010. SUBJECTS: Nationally representative samples of Australian households. RESULTS: The share of the total food budget spent on food away from home rose steadily from 22.8 % in 1989 to 26.5 % in 2010, while spending on ultra processed foods increased. The basic patterning of meals and the pace of eating changed little, although people spent more time eating alone and at restaurants. Cooking time declined considerably, particularly for women. CONCLUSIONS: These changes have occurred over the same time that obesity and diet-related, non communicable diseases have increased rapidly in Australia. Some aspects are implicated more than others: particularly the shift from domestic cooking to use of pre-prepared and ultra-processed foods, a reduction in time spent in food preparation and cooking, as well as an upsurge in time and money devoted to eating away from home. These are all likely to operate through the higher energy content of commercially prepared, compared with unprocessed or lightly processed, foods. PMID- 27652994 TI - Rehabilitation during congenital heart disease in pediatric patients. AB - Cardiac rehabilitation is an important part of daily routine for cardiac disorder patients in adults. However, pediatric rehabilitation is an emerging field, and is totally different and new field in case of pediatric patients. The main reason of variability is the Pediatric patients differ from adult patients in several ways. The main difference is they are dependent on their parents for meeting their needs, including for transportation and following of rehabilitation initiatives. Furthermore, rehabilitation initiatives are often connected to large urban university hospitals and unavailable to children whose parents cannot bring them for exercise training on a regular basis. The present review article is focused on these aspects of rehabilitation during congenital heart disease. PMID- 27652995 TI - Association between Number of Formed Embryos, Embryo Morphology and Clinical Pregnancy Rate after Intracytoplasmic Sperm Injection. AB - Introduction Infertility has a high prevalence in the general population, affecting ~ 5 to 15% of couples in reproductive age. The assisted reproduction techniques (ART) include in vitro manipulation of gametes and embryos and are an important treatment indicated to these couples. It is well accepted that the implantation rate is positively influenced by the morphology of transferred embryos. However, we question if, apart from the assessment of embryo morphology, the number of produced embryos per cycle is also related to pregnancy rates in the first fresh transfer cycle. Purpose To evaluate the clinical pregnancy rate according to the number of formed embryos and the transfer of top quality embryos (TQEs). Methods In a retrospective cohort study, between January 2011 and December 2012, we evaluated women who underwent intracytoplasmic sperm injection (ICSI), aged < 40 years, and with at least 1 formed embryo fresh transferred in cleavage stage. These women were stratified into 3 groups according to the number of formed embryos (1 embryo, 2-3 and >= 4 embryos). Each group was divided into 2 subgroups according to the presence or not of at least 1 transferred TQE (1 with TQE; 1 without TQE; 2-3 with TQE, 2-3 without TQE; >= 4 with TQE; >= 4 without TQE). The clinical pregnancy rates were compared in each subgroup based on the presence or absence of at least one transferred TQE. Results During the study period, 636 women had at least one embryo to be transferred in the first fresh cycle (17.8% had 1 formed embryo [32.7% with TQE versus 67.3% without TQE], 42.1% of women had 2-3 formed embryos [55.6% with TQE versus 44.4% without TQE], and 40.1% of patients had >= 4 formed embryos [73.7% with TQE versus 26.3% without TQE]). The clinical pregnancy rate was significantly higher in the subgroup with >= 4 formed embryos with at least 1 transfered TQE (45.2%) compared with the subgroup without TQE (28.4%). Conclusions Having at least two available embryos and at least one TQE for embryo transfer are predictors of the pregnancy rates. PMID- 27652996 TI - A General Strategy for Decoupled Hydrogen Production from Water Splitting by Integrating Oxidative Biomass Valorization. AB - Conventional water electrolyzers produce H2 and O2 simultaneously, such that additional gas separation steps are needed to prevent H2/O2 mixing. The sluggish anodic O2 evolution reaction (OER) always results in low overall energy conversion efficiency and the product of OER, O2, is not of significant value. In addition, the potential formation of reactive oxygen species (ROS) may lead to degradation of cell membranes and thus premature device failure. Herein we report a general concept of integrating oxidative biomass upgrading reactions with decoupled H2 generation from water splitting. Five representative biomass substrates, ethanol, benzyl alcohol, furfural, furfuryl alcohol, and 5 hydroxymethylfurfural (HMF), were selected for oxidative upgrading catalyzed by a hierarchically porous Ni3S2/Ni foam bifunctional electrocatalyst (Ni3S2/NF). All the five organics can be oxidized to value-added liquid products at much lower overpotentials than that of OER. In particular, the electrocatalytic oxidation of HMF to the value-added 2,5-furandicarboxylic acid (FDCA) was further studied in detail. Benefiting from the more favorable thermodynamics of HMF oxidation than that of OER, the cell voltage for integrated H2 production and HMF oxidation was significantly reduced by ~200 mV relative to pure water splitting to achieve 100 mA cm-2, while the oxidation product (FDCA) at the anode was much more valuable than O2. When utilized as electrocatalysts for both cathode and anode, Ni3S2/NF demonstrated outstanding durability and nearly unity Faradaic efficiencies for both H2 and FDCA production. Overall, such an integration of oxidative biomass valorization and HER via earth-abundant electrocatalysts not only avoids the generation of explosive H2/O2 mixture and ROS, but also yields products of high value at both electrodes with lower voltage input, maximizing the energy conversion efficiency. PMID- 27652997 TI - Polarity-Tunable Host Materials and Their Applications in Thermally Activated Delayed Fluorescence Organic Light-Emitting Diodes. AB - A series of polarity-tunable host materials were developed based on oligocarbazoles and diphenylphosphine oxide, and their polarities can be tuned through increasing distance of acceptor and donor units. Density functional theory calculations were employed, and photoluminescence spectra in different polar solvents were measured to illustrate different polarities of these host materials. As CZPO has relatively stronger polarity, electroluminescence (EL) spectrum of solution-processed device based on 6 wt % PXZDSO2:CZPO is 7 nm red shifted relative to that of other host materials based devices. Besides, a comparable impressive external quantum efficiency (EQE) value of 18.7% is achieved for an evaporation-processed yellow device consisting of FCZBn, which is superior to that of the device based on CBP (4,4'-dicarbazolyl-1,1'-biphenyl) (17.0%), and its efficiency roll-off is also obviously reduced, giving an EQE value as high as 16.3% at the luminance of 1000 cd/m2. In addition, from CZPO to FCZBn as the polarities of host materials decrease, EL spectra of solution processed devices based on DMAC-DPS emitter blue-shift constantly from 496 to 470 nm. The current work gives a constructive approach to control EL spectra of organic light-emitting diodes with a fixed thermally activated delayed fluorescence emitter by tuning the polarities of host materials. PMID- 27652998 TI - Nitrate Photolysis in Salty Snow. AB - Nitrate photolysis from snow can have a significant impact on the oxidative capacity of the local atmosphere, but the factors affecting the release of gas phase products are not well understood. Here, we report a systematic study of the amounts of NO, NO2, and total nitrogen oxides (NOy) emitted from illuminated snow samples as a function of both nitrate and total salt (NaCl and Instant Ocean) concentration. The results provide experimental evidence that the release of nitrogen oxides to the gas phase is directly related to the expected nitrate concentration in the brine at the surface of the snow crystals. With no added salts, steady-state release of gas-phase products increases to a plateau value with increasing prefreezing nitrate concentration; with the addition of salts, the steady-state gas-phase nitrogen oxides generally decrease with increasing prefreezing NaCl or Instant Ocean concentration. In addition, for these frozen mixed nitrate (25 mM)-salt (0-500 mM) solutions, there is an increase in gas phase NO2 seen at low added salt amounts, with NO2 production enhanced by up to 42% at low prefreezing [NaCl] (<=25 mM) and by up to 89% at prefreezing Instant Ocean concentrations lower than 200 mM [Cl-]. This enhancement may be important to the atmospheric oxidative capacity in polar regions. PMID- 27652999 TI - FGF-23 and cardiovascular disease: review of literature. AB - PURPOSE OF REVIEW: This review examines associations between fibroblast growth factor 23 (FGF-23) and cardiovascular disease. RECENT FINDINGS: FGF-23 is a hormone produced by osteocytes and osteoblasts that aids with phosphate excretion by the kidney and acts as a negative feedback regulator for activated vitamin D synthesis. Recent studies have found associations between elevated FGF-23 levels and a number of cardiovascular diseases, including hypertension, left ventricular hypertrophy, endothelial dysfunction, cardiovascular events and mortality. CONCLUSION: Recent studies have explored the possible effects of FGF-23 on the cardiovascular system. In animal and observational human studies, there is a link between elevated FGF-23 levels and multiple cardiovascular outcomes, including hypertension, left ventricular hypertrophy and cardiovascular events and mortality. Further studies are required to evaluate whether decreasing FGF-23 levels improves cardiovascular outcomes. PMID- 27653001 TI - Ethics of medical and nonmedical oocyte cryopreservation. AB - PURPOSE OF REVIEW: To assess the effectiveness and ethical dimensions of oocyte cryopreservation for both medical and social indications. RECENT FINDINGS: As more women are postponing motherhood for a variety of reasons, including lack of partner, for completing career plans and reaching financial stability, they are resorting to oocyte cryopreservation. To make informed choices, women rely on their primary care physicians (PCPs) for initial advice, but PCPs are not always fully prepared to discuss oocyte cryopreservation. Interestingly, there are mixed feelings among obstetricians/gynecologists on whether oocyte cryopreservation should be used for elective reasons, whereas it is fully supported for medical indications. SUMMARY: Oocyte vitrification has become an established procedure for safeguarding future reproductive chances for medical reasons, and its use is progressively expanding. There is an urgent need in preparing future PCPs and obstetricians/gynecologists as to how to initiate discussions with their patients about elective oocyte banking consistent with fully respecting patient autonomy so as to facilitate informed decisions. PMID- 27653000 TI - An update on vitamin D for clinicians. AB - PURPOSE OF REVIEW: The clinical benefits of vitamin D therapy have received substantial attention over the past decade. Recently, several trials looked to clarify the optimal vitamin D dose or serum level needed to promote human health. The purpose of this review is to highlight selected studies published since January 2015. RECENT FINDINGS: Several recent trials challenge whether serum vitamin D levels at least 30 ng/ml promote human health. In postmenopausal women with 25-hydroxyvitamin D [25(OH)D] levels 21 +/- 3 ng/ml, high-dose vitamin D for 1 year increased calcium absorption by 1%, without changes in bone mineral density, physical function, or falls when compared with low-dose vitamin D and placebo. High-dose vitamin D increased risk of falling in 200 adults 78 +/- 5 years old with baseline 25(OH)D levels of ~19 +/- 9 ng/ml. High-dose vitamin D in adults increased the number and duration of upper respiratory tract infections compared with placebo. Asthma patients achieving 25(OH)D levels more than 30 ng/ml during a trial experienced more respiratory infections than those not achieving such levels. SUMMARY: Recent studies are congruent with the Institute of Medicine's conclusion that humans are vitamin D replete when their serum 25(OH)D levels are at least 20 ng/ml. Higher levels seem to promote falls and respiratory infections. PMID- 27653002 TI - Evolution of human oocyte cryopreservation: slow freezing versus vitrification. AB - PURPOSE OF REVIEW: The purpose is to determine the efficiency and efficacy of oocyte cryopreservation by slow freezing versus vitrification, recent data collected from the Italian National Assisted Reproductive Technology Register during the period 2009-2014 will be presented and reviewed. The data on oocyte cryopreservation were also compared with the results obtained with embryo cryopreservation and relative IVF with fresh oocytes. RECENT FINDINGS: During the period 2009-2014 preservation of oocytes by vitrification had a significantly higher survival rate, implantation, and pregnancy rate than slow freezing; however, there are still large variations in success rates among centers in relation to the number of procedures performed. SUMMARY: Vitrification has now become the method of choice for oocyte cryopreservation because of better results than slow freezing, but still requires a more standardized utilization. The transfer of fresh or cryopreserved embryo still shows a statistically significant better performance than transfers with embryos obtained with cryopreserved oocytes. Only in a few centers with much experience in cryopreservation are the results between transfers of frozen embryos or embryos obtained from oocyte cryopreservation comparable. PMID- 27653003 TI - Bisphosphonates and atypical femoral fractures. AB - PURPOSE OF REVIEW: Bisphosphonates are used widely for the treatment of osteoporosis and prevention of fractures. Although generally well tolerated and effective, bisphosphonates (and denosumab, a newer antiresorptive agent) have been associated with unusual fractures of the femoral shaft. RECENT FINDINGS: New information about the incidence, pathophysiology, and management of atypical femoral fractures (AFFs) are reviewed. Histomorphometric studies have shown variable amounts of bone turnover suppression, but new studies suggest that healing near bone cracks may not occur in patients with AFF. Some studies suggest that hip and femur geometry make certain people more at risk for AFF. In some but not all studies, the risk of AFF appears to be related to duration of treatment. Thus, the benefit/risk ratio needs to be reassessed as bisphosphonate therapy is prolonged. SUMMARY: If we can better understand the pathogenesis of AFF, it may be possible to identify those patients at highest risk. In the meantime, clinicians must periodically assess risk for osteoporotic fracture versus risk for AFF in managing patients with osteoporosis. PMID- 27653004 TI - Crossword Puzzle. PMID- 27653005 TI - Clinical Effect of Sex-Specific Cutoff Values of High-Sensitivity Cardiac Troponin T in Suspected Myocardial Infarction. AB - Importance: It is currently unknown whether the uniform (universal clinical practice for more than 2 decades) or 2 sex-specific cutoff levels are preferable when using high-sensitivity cardiac troponin T (hs-cTnT) levels in the diagnosis of acute myocardial infarction (AMI). Objective: To improve the management of suspected AMI in women by exploring sex-specific vs uniform cutoff levels for hs cTnT. Design, Setting, and Participants: In an ongoing prospective, diagnostic, multicenter study conducted at 9 emergency departments, the present study evaluated patients enrolled from April 21, 2006, through June 5, 2013. The participants included 2734 adults presenting with suspected AMI. Duration of follow-up was 2 years, and data analysis occurred from June 5 to December 21, 2015. Interventions: The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including measurements of serial hs-cTnT blood concentrations twice: once using the uniform 99th percentile cutoff value level of 14 ng/L and once using sex-specific 99th percentile levels of hs-cTnT (women, 9 ng/L; men, 15.5 ng/L). Main Outcomes and Measures: Diagnostic reclassification in women and men using sex-specific vs the uniform cutoff level in the diagnosis of AMI. Results: Of the 2734 participants, 876 women (32%) and 1858 men (68%) were included. Median (interquartile range) age was 68 (55-77) and 59 (48-71) years, respectively. With the use of the uniform cutoff value, 127 women (14.5%) and 345 men (18.6%) received a final diagnosis of AMI. Among these, at emergency department presentation, levels of hs cTnT were already above the uniform cutoff value in 427 patients (sensitivity, 91.3% [95% CI, 85%-95.6%] in women vs 90.7% [95% CI, 87.1%-93.5% in men]; specificity, 79.2% [95% CI, 76.1%-82.1%] in women vs 78.5% [95% CI, 76.4%-80.6%] in men). After readjudication using sex-specific 99th percentile levels, diagnostic reclassification regarding AMI occurred in only 3 patients: 0.11% (95% CI, 0.02-0.32) of all patients and 0.6% (95% CI, 0.13-1.85) of patients with AMI. The diagnosis in 2 women was upgraded from unstable angina to AMI, and the diagnosis in 1 man was downgraded from AMI to unstable angina. These diagnostic results were confirmed when using 2 alternative pairs of uniform and sex-specific cutoff values. Conclusions and Relevance: The uniform 99th percentile should remain the standard of care when using hs-cTnT levels for the diagnosis of AMI. PMID- 27653007 TI - Codman, Hawthorne, and End Results of a Watched System. PMID- 27653006 TI - Association Between Hospital Participation in a Medicare Bundled Payment Initiative and Payments and Quality Outcomes for Lower Extremity Joint Replacement Episodes. AB - IMPORTANCE: Bundled Payments for Care Improvement (BPCI) is a voluntary initiative of the Centers for Medicare & Medicaid Services to test the effect of holding an entity accountable for all services provided during an episode of care on episode payments and quality of care. OBJECTIVE: To evaluate whether BPCI was associated with a greater reduction in Medicare payments without loss of quality of care for lower extremity joint (primarily hip and knee) replacement episodes initiated in BPCI-participating hospitals that are accountable for total episode payments (for the hospitalization and Medicare-covered services during the 90 days after discharge). DESIGN, SETTING, AND PARTICIPANTS: A difference-in differences approach estimated the differential change in outcomes for Medicare fee-for-service beneficiaries who had a lower extremity joint replacement at a BPCI-participating hospital between the baseline (October 2011 through September 2012) and intervention (October 2013 through June 2015) periods and beneficiaries with the same surgical procedure at matched comparison hospitals. EXPOSURE: Lower extremity joint replacement at a BPCI-participating hospital. MAIN OUTCOMES AND MEASURES: Standardized Medicare-allowed payments (Medicare payments), utilization, and quality (unplanned readmissions, emergency department visits, and mortality) during hospitalization and the 90-day postdischarge period. RESULTS: There were 29 441 lower extremity joint replacement episodes in the baseline period and 31 700 in the intervention period (mean [SD] age, 74.1 [8.89] years; 65.2% women) at 176 BPCI-participating hospitals, compared with 29 440 episodes in the baseline period (768 hospitals) and 31 696 episodes in the intervention period (841 hospitals) (mean [SD] age, 74.1 [8.92] years; 64.9% women) at matched comparison hospitals. The BPCI mean Medicare episode payments were $30 551 (95% CI, $30 201 to $30 901) in the baseline period and declined by $3286 to $27 265 (95% CI, $26 838 to $27 692) in the intervention period. The comparison mean Medicare episode payments were $30 057 (95% CI, $29 765 to $30 350) in the baseline period and declined by $2119 to $27 938 (95% CI, $27 639 to $28 237). The mean Medicare episode payments declined by an estimated $1166 more (95% CI, -$1634 to -$699; P < .001) for BPCI episodes than for comparison episodes, primarily due to reduced use of institutional postacute care. There were no statistical differences in the claims-based quality measures, which included 30-day unplanned readmissions (-0.1%; 95% CI, -0.6% to 0.4%), 90-day unplanned readmissions (-0.4%; 95% CI, -1.1% to 0.3%), 30-day emergency department visits (-0.1%; 95% CI, -0.7% to 0.5%), 90-day emergency department visits (0.2%; 95% CI, -0.6% to 1.0%), 30-day postdischarge mortality (-0.1%; 95% CI, -0.3% to 0.2%), and 90-day postdischarge mortality (-0.0%; 95% CI, -0.3% to 0.3%). CONCLUSIONS AND RELEVANCE: In the first 21 months of the BPCI initiative, Medicare payments declined more for lower extremity joint replacement episodes provided in BPCI-participating hospitals than for those provided in comparison hospitals, without a significant change in quality outcomes. Further studies are needed to assess longer-term follow-up as well as patterns for other types of clinical care. PMID- 27653008 TI - Minimally Invasive Spine Surgery (MISS) in China. PMID- 27653009 TI - Minimally Invasive Pedicle Screws Fixation and Percutaneous Vertebroplasty for the Surgical Treatment of Thoracic Metastatic Tumors With Neurologic Compression. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: To describe minimally invasive pedicle screw fixation (MIPS) combined with percutaneous vertebroplasty (PVP), minimally invasive decompression and partial tumor resection for the treatment of thoracic metastasis with symptoms of neurologic compression and evaluate the feasibility, efficacy, and safety. SUMMARY OF BACKGROUND DATA: Neurologic decompression, spinal tumor resection, and stabilization with instrumentation should be performed from an anterior, a posterior, or a combined approach for spinal metastatic tumors with symptoms of neurologic compression. These operations, however, have significant morbidity related to the surgical approach, potential blood loss, extensive dissection, or biomechanical instability. METHODS: Eighteen patients who sustained single-level thoracic vertebral metastasis and neurologic compression underwent MIPS (The minimal-access in a paraspinal sacrospinalis muscle-splitting approach was performed to insert the pedicle screws into the vertebrae under direct vision and two rods of appropriate size were placed over the pedicle screws through subcutaneous soft tissues and muscles) combined with PVP, minimally invasive neurologic decompression, and partial tumor resection. The patients were evaluated preoperatively according to the Tomita, revised Tokuhashi, Bilsky grading system, and Spinal Instability Neoplastic Score. Pre- and postoperative VAS score, American Spinal Injury Association grade, ambulatory status, and urinary continence were also recorded. The Cobb angles, central, and anterior vertebral body height were measured on the lateral radiographs before surgery and during the follow-up. RESULTS: Clinical follow-up was available for 17 patients in this study ranging from 12 to 16 months (mean time, 14.2 months), and 1 patient died 8 months after surgery. The Visual Analog Scale was significantly decreased after surgery. Improvement of paraplegia was observed after surgery in all of these patients. Spine stability was observed in all of the surviving patients during the follow-up. CONCLUSION: MIPS combined with PVP, minimally invasive decompression, and partial tumor resection is a good choice of surgical treatment of thoracic metastatic tumors with neurologic compression. LEVEL OF EVIDENCE: 2. PMID- 27653010 TI - Application of Laparoscopic Lumbar Discectomy and Artificial Disc Replacement: At Least Two Years of Follow-Up. AB - STUDY DESIGN: This prospective observational study included 22 patients who were diagnosed with symptomatic degenerative disc disease treated via artificial disc replacement (ADR) with a laparoscopic technique. OBJECTIVE: The current study aimed to assess the safety and efficacy of ADR using a laparoscopic technique for lumbar disc herniation. SUMMARY OF BACKGROUND DATA: Symptomatic degenerative disc disease is the major cause of low back pain with lumbar segmental instability. ADR has increased in popularity as an alternative treatment for lumbar disc herniation. However, the traditional approach to spinal surgery carries the risk of catastrophic bleeding from injury to major vessels, as well as iatrogenic injury to the viscera and associated structures. Therefore, laparoscopic lumbar discectomy and ADR may represent a useful alternative. METHODS: Twenty-two patients (8 males and 14 females) who were diagnosed with symptomatic degenerative disc disease were included in this study. Seven cases involved the L4/5 level, and 15 cases involved the L5/S1 level. All patients were ineffective after at least 6 months of conservative treatments; all patients were informed of the surgery before the operation and provided consent. Three-dimensional computed tomographic angiography (3D-CTA) of the iliac great blood vessels was completed before the surgery. All surgical procedures were performed under a laparoscope. All patients were followed up. RESULTS: All surgeries were successfully completed. The average operation time was 120 minutes (range 110-150 min), and the average hemorrhage was 145 mL (range 80-360 mL). All cases underwent X-rays at 3 days, 3 months, 6 months, 1 year, and the final postoperative follow-up. The outcome indicated that there was no mobilization, displacement, or subsidence in all patients with the exception of one case with prosthesis migration. The follow up time was 43.8 months (range 24-64 months). The mean visual analog scale (VAS) and Oswestry scores were decreased postoperatively. The mean improvement rate of the VAS score was 73.5%. CONCLUSION: Lumbar ADR using a laparoscope represents a novel, minimally invasive treatment for symptomatic degenerative disc disease and severe lumbar discogenic pain. PMID- 27653011 TI - Cyclo[4]carbazole, an Iodide Anion Macrocyclic Receptor. AB - A novel preorganized and rigid iodide anion macrocyclic receptor, cyclo[4]carbazole (Cy[4]C), is reported here. The structure of Cy[4]C was confirmed by single-crystal X-ray analysis. The binding affinity of Cy[4]C for iodide anion was investigated by UV-vis and 1H NMR spectroscopic techniques. The crystal structure of the complex between Cy[4]C and chloroform also provided evidence for the recognition ability of Cy[4]C toward iodide anion. Furthermore, the 1:1 complexation stoichiometry between Cy[4]C and iodide anion was confirmed by high-resolution mass spectrometry and molecular modeling. PMID- 27653012 TI - Processes and conditions underlying the link between shyness and school adjustment among Turkish children. AB - This study examined the underlying processes and conditions that contribute to the school adjustment of shy children in Turkey, where children's interpersonal relationships in social settings and academic achievement are highly emphasized. First, we examined the unique mediating roles of children's feelings of social anxiety, depressive symptoms, and loneliness in the associations between shyness and indices of school outcomes (academic achievement and school liking/avoidance). Second, we explored the moderating role of children's peer acceptance in these associations. Fourth- and fifth-grade children (N = 599; Mage = 10.11 years, SD = 0.65; 48% girls) provided information on shyness, social anxiety, depressive symptoms, loneliness, and school liking/avoidance. Head teachers in each classroom reported on students' academic performance. The peer nomination method was used to assess children's peer relationships. Results revealed that when children displayed shy behaviours, they reported more depressive symptoms that were, in turn, associated with poorer academic performance, less school liking, and higher school avoidance. Moreover, shyness negatively predicted school liking at low levels of peer acceptance, suggesting that difficulties in peer relationships increased shy children's risk of school dissatisfaction. Overall, our findings support the importance of the interpersonal relationship context for children's adjustment within the Turkish cultural context. Statement of contribution What is already known on this subject? Shy children have difficulties initiating and maintaining social interactions, which put them at risk for a wide range of socio-emotional difficulties. Shy children have poor academic performance and experience school adjustment difficulties in North America. What does this study add? Shyness is an important risk factor for poorer academic performance and adjustment among children in Turkey. The association between shyness and difficulties at school is explained by children's experience of depressive symptoms. Difficulties with peer relationships increase shy children's risk of school dissatisfaction. PMID- 27653013 TI - Enhancing self-care, adjustment and engagement through mobile phones in youth with HIV. AB - AIM: To evaluate the effectiveness of mobile phones in enhancing self-care, adjustment and engagement in non-disclosed youth living with HIV. BACKGROUND: Youth aged 15-24 years represent 42% of new HIV infections globally. Youth who are aware of their HIV status generally do not disclose it or utilize HIV-related facilities because of fear of stigma. They rely on the Internet for health maintenance information and access formal care only when immune-compromised and in crisis. INTRODUCTION: This study shows how non-disclosed youth living with HIV can be reached and engaged for self-management and adjustment through mobile phone. STUDY DESIGN: One-group pre-test/post-test experimental design was used. METHODS: Mobile phones were used to give information, motivation and counselling to 19 purposively recruited non-disclosed youth with HIV in Calabar, South-South Nigeria. Psychological adjustment scale, modified self-care capacity scale and patient activation measure were used to collect data. Data were analysed using PASW 18.0. RESULTS: Scores on self-care capacity, psychological adjustment and engagement increased significantly at post-test. HIV-related visits to health facilities did not improve significantly even at 6 months. Participants still preferred to consult healthcare providers for counselling through mobile phone. DISCUSSION: Mobile phone-based interventions are low cost, convenient, ensure privacy and are suitable for youth. Such remote health counselling enhances self management and positive living. CONCLUSION AND IMPLICATIONS FOR HEALTH POLICY: Mobile phones enhance self-care, psychological adjustment and engagement in non disclosed youth living with HIV, and can be used to increase care coverage. Findings underline the importance of policies to increase access by locating, counselling and engaging HIV-infected youth in care. PMID- 27653014 TI - Interesting microorganism. PMID- 27653016 TI - Crystal Growth, Structure, Resistivity, Magnetic, and Photoelectric Properties of One-Dimensional Selenometallate Ba2 BiFeSe5. AB - Low-dimensional materials have attracted extensive research interest in recent years owing to their interesting structural chemistry and physical properties, which will greatly deepen our knowledge of these materials and could lead to additional breakthroughs in the future. Herein we have synthesized and characterized Ba2 BiFeSe5 , which adopts a quasi-one-dimensional structure and possesses some fascinating physical properties. The sharp divergences between the field-cooled (FC) and the zero-field-cooled (ZFC) data and the rather small magnetic moment per Fe3+ (0.07 MUB ) strongly suggest that the title compound is weakly ferromagnetic with a high magnetic transition temperature above room temperature, which is controlled by competing super-exchange interactions within and between [FeBiSe5 ]infinity anionic ladders. Moreover, with its narrow bandgap of 0.95 eV, Ba2 BiFeSe5 shows photoelectric properties with a photocurrent density of approximately 30 mA cm2 at 5 V. Our study demonstrates that Ba2 FeBiSe5 might be a new type of multifunctional material that deserves further investigation. PMID- 27653017 TI - Herpes simplex infection on a recent tattoo. A new case of "herpes compuctorum". PMID- 27653018 TI - Extremely Active Organocatalysts Enable a Highly Enantioselective Addition of Allyltrimethylsilane to Aldehydes. AB - The enantioselective allylation of aldehydes to form homoallylic alcohols is one of the most frequently used carbon-carbon bond-forming reaction in chemical synthesis and, for several decades, has been a testing ground for new asymmetric methodology. However, a general and highly enantioselective catalytic addition of the inexpensive, nontoxic, air- and moisture-stable allyltrimethylsilane to aldehydes, the Hosomi-Sakurai reaction, has remained elusive. Reported herein is the design and synthesis of a highly acidic imidodiphosphorimidate motif (IDPi), which enables this transformation, thus converting various aldehydes with aromatic and aliphatic groups at catalyst loadings ranging from 0.05 to 2.0 mol % with excellent enantioselectivities. Our rationally constructed catalysts feature a highly tunable active site, and selectively process small substrates, thus promising utility in various other challenging chemical reactions. PMID- 27653015 TI - Peroxiredoxin 1 - an antioxidant enzyme in cancer. AB - Peroxiredoxins (PRDXs), a ubiquitous family of redox-regulating proteins, are reported of potential to eliminate various reactive oxygen species (ROS). As a major member of the antioxidant enzymes, PRDX1 can become easily over-oxidized on its catalytically active cysteine induced by a variety of stimuli in vitro and in vivo. In nucleus, oligomeric PRDX1 directly associates with p53 or transcription factors such as c-Myc, NF-kappaB and AR, and thus affects their bioactivities upon gene regulation, which in turn induces or suppresses cell death. Additionally, PRDX1 in cytoplasm has anti-apoptotic potential through direct or indirect interactions with several ROS-dependent (redox regulation) effectors, including ASK1, p66Shc , GSTpi/JNK and c-Abl kinase. PRDX1 is proven to be a versatile molecule regulating cell growth, differentiation and apoptosis. Recent studies have found that PRDX1 and/or PRDX1-regulated ROS-dependent signalling pathways play an important role in the progression and metastasis of human tumours, particularly in breast, oesophageal and lung cancers. In this paper, we review the structure, effector functions of PRDX1, its role in cancer and the pivotal role of ROS in anticancer treatment. PMID- 27653019 TI - The learning curves in living donor hemiliver graft procurement using small upper midline incision. AB - The learning curve for performing living donor hemiliver procurement (LDHP) via small upper midline incision (UMI) has not been determined. Living donors (n=101) who underwent LDHP via UMI were included to investigate the learning curve using cumulative sum analysis. The cumulative sum analysis showed that nine cases for right lobe (case #23) and 19 cases for left lobe (case #32 in the whole series) are needed for stable and acceptable surgical outcomes in LDHP via UMI. The established phase (n=69, since case #33) had a significantly shorter operative time, a smaller incision size, and less blood loss than the previous learning phase (n=32, serial case number up to the last 19th left lobe case). Multivariate analysis showed that the learning phase, high body mass index >=25 kg/m2 , and left lobe graft procurement are the factors associated with surgical events including operative blood loss >=400 mL, operative time >=300 minutes, or surgical complications >=Clavien-Dindo grade II. There is an obvious learning curve in performing LDHP via UMI, and 32 cases including both 19 cases for left lobe and nine cases for right lobe are needed for having stable and acceptable surgical outcomes. PMID- 27653020 TI - Adopting an external focus of attention alters intracortical inhibition within the primary motor cortex. AB - AIM: Although it is well established that an external (EF) compared to an internal (IF) or neutral focus of attention enhances motor performance, little is known about the underlying neural mechanisms. This study aimed to clarify whether the focus of attention influences not only motor performance but also activity of the primary motor cortex (M1) when executing identical fatiguing tasks of the right index finger (first dorsal interosseous). Transcranial magnetic stimulation (TMS) at intensities below motor threshold was applied over M1 to assess and compare the excitability of intracortical inhibitory circuits. METHODS: In session 1, 14 subjects performed an isometric finger abduction at 30% of their maximal force to measure the time to task failure (TTF) with either an IF or EF. In session 2, the same task was performed with the other focus. In sessions 3 and 4, subthreshold TMS (subTMS) and paired-pulse TMS were applied to the contralateral M1 to compare the activity of cortical inhibitory circuits within M1 during EF and IF. RESULTS: With an EF, TTF was significantly prolonged (P = 0.01), subTMS-induced electromyographical suppression enhanced (P = 0.001) and short-interval intracortical inhibition (SICI) increased (P = 0.004). CONCLUSION: The level of intracortical inhibition was previously shown to influence motor performance. Our data shed new light on the ability to instantly modulate the activity of inhibitory circuits within M1 by changing the type of attentional focus. The increased inhibition with EF might contribute to the better movement efficiency, which is generally associated with focusing externally. PMID- 27653021 TI - Mathematics as a conduit for translational research in post-traumatic osteoarthritis. AB - Biomathematical models offer a powerful method of clarifying complex temporal interactions and the relationships among multiple variables in a system. We present a coupled in silico biomathematical model of articular cartilage degeneration in response to impact and/or aberrant loading such as would be associated with injury to an articular joint. The model incorporates fundamental biological and mechanical information obtained from explant and small animal studies to predict post-traumatic osteoarthritis (PTOA) progression, with an eye toward eventual application in human patients. In this sense, we refer to the mathematics as a "conduit of translation." The new in silico framework presented in this paper involves a biomathematical model for the cellular and biochemical response to strains computed using finite element analysis. The model predicts qualitative responses presently, utilizing system parameter values largely taken from the literature. To contribute to accurate predictions, models need to be accurately parameterized with values that are based on solid science. We discuss a parameter identification protocol that will enable us to make increasingly accurate predictions of PTOA progression using additional data from smaller scale explant and small animal assays as they become available. By distilling the data from the explant and animal assays into parameters for biomathematical models, mathematics can translate experimental data to clinically relevant knowledge. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:566-572, 2017. PMID- 27653022 TI - Management of Hypertension With a Fixed-Dose (Single-Pill) Combination of Bisoprolol and Amlodipine. AB - Hypertension is currently one of the greatest global health care challenges. Although many effective drugs are available, combinations of 2 or more medications are often required to meet clinical targets. Combination therapy has several advantages over monotherapy: lower doses of each drug can be used to achieve therapeutic goals; lower doses may lead to fewer adverse events, facilitating patient adherence; and using multiple drugs with different modes of action may be more effective in treating multifactorial diseases, including hypertension. Adherence is an important consideration when requiring patients to self-administer multiple medications; as the number of concurrent medications increases, patient adherence tends to decrease. Recent evidence suggests that fixed-dose combinations (FDCs) may be more effective than free-dose combinations, as they provide all necessary medications in a single convenient tablet/single pill combination. Among combinations of hypertension medications, a beta-blocker such as bisoprolol with a calcium channel blocker such as amlodipine is an effective combination therapy for hypertension, with distinct and complimentary modes of action. With advantages over free-dose combinations, the FDC of bisoprolol/amlodipine is thus an effective and convenient treatment for hypertension, allowing more patients to achieve their therapeutic goals, while potentially reducing the burden of hypertension on health care systems. PMID- 27653024 TI - Retinal microcirculation in association with caffeinated and alcoholic drinks in subjects at increased cardiovascular risk. AB - OBJECTIVES: The association of caffeinated and alcoholic drinks with microcirculation is poorly investigated. The aim of the study was to investigate the associations of daily consumption of caffeinated and alcoholic drinks with retinal vessel calibers. METHODS: In consecutive adults at increased risk but free of CVD and diabetes mellitus, (n=181, age: 51.32+/-12.42 y, 51.4% women), we determined CRAE, CRVE and AVR, respectively. Daily consumption of caffeinated and alcoholic drinks was assessed through 24 h recalls. RESULTS: After adjustment for potential confounders: (i) caffeine was positively associated with CRVE (b=0.177, P=.006 for left, b=0.208, P=.002 for right eye, respectively) (ii) decaffeinated coffee was positively associated with CRAE (b=0.141, P=.035 for left eye) and negatively associated with CRVE (b=-0.234, P<.001 for left, b=-0.189, P=.006 for right eye, respectively). Regular coffee, tea, alcohol, and any type of alcoholic drink did not associate with retinal vessel calibers. CONCLUSIONS: Alcohol and alcoholic drinks' consumption were not associated, while decaffeinated coffee and caffeine consumption were associated in an opposing pattern with retinal vessel calibers. The reason of this controversy merits further investigation. PMID- 27653025 TI - Erratum. PMID- 27653023 TI - DDR2-CYR61-MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast-Like Synoviocytes. AB - Regulation of matrix metalloproteinases (MMPs) by collagen in the fibroblast-like synoviocytes (FLSs) plays a critical role in joint destruction in rheumatoid arthritis (RA). Our previous study indicated that discoidin receptor 2 (DDR2) mediated collagen upregulation of MMPs. However, the precise underlying mechanism remains unclear. We report here that CYR61, a secreted, extracellular matrix associated signaling protein which is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, and apoptosis, is significantly upregulated in collagen II-stimulated RA FLS. Further studies found that collagen II-activated phosphorylated-DDR2 induces CYR61 through activation of transcription factor activator protein 1 (AP-1). The elevated CYR61, in turn, accelerates MMP1 production via ETS1 (ETS proto-oncogene 1). In addition, CYR61 significantly promotes FLS invasion and migration. Blockade of CYR61 by an adenovirus expressing CYR61 shRNA (Ad-shCYR61) in vivo remarkably ameliorated the severity of arthritis, reduced inflammatory cytokine secretion, and attenuated bone erosion as detected by micro-computed tomography (MUCT), in collagen-induced arthritis (CIA) rats. Taken together, we uncovered the Collagen II-DDR2-AP-1-CYR61-ETS1-MMP1 loop in RA FLS. In which, CYR61 acts as a hinge to promote cartilage damage through regulating FLS invasion, migration, and MMP1 production and the inflammatory cascade in RA. Thus, CYR61 may be a promising diagnostic and therapeutic target for RA treatment. (c) 2016 American Society for Bone and Mineral Research. PMID- 27653026 TI - Isotopic Combinatomer Analysis Provides in Vivo Evidence of the Direct Epimerization of Monoglucosyl Diacylglycerol in Cyanobacteria. AB - Galactolipids constitute the majority of photosynthetic membranes called thylakoid membranes in cyanobacteria and chloroplasts of land plants and algae. The galactolipids, although identical in headgroup structure, are synthesized by significantly different pathways in cyanobacteria and chloroplasts. In the cyanobacterial pathway, monoglucosyl diacylglycerol (GlcDG) is synthesized first and then converted to monogalactosyl diacylglycerol (MGDG). On the basis of circumstantial evidence, the mechanism of conversion was thought to be epimerization at C-4, but no direct evidence has yet been provided, because there is no in vitro enzymatic system of the putative membrane-bound reaction. Labeling studies with 14C and 13C suggested that the labels in the headgroup and the acyl groups were kept at a reasonably constant ratio before and after the conversion. We then provide in vivo evidence of the direct epimerization based on detailed isotopomer analysis of the conversion, named "combinatomer analysis". The different types of molecules formed by the combination of labeled or unlabeled parts (sn-1 acyl, sn-2 acyl, glycerol, and hexose) are called here "combinatomers". Combinatomer analysis of the experiments with pulse labeling with 13C and chase in Anabaena sp. PCC 7118 indicated that the composition of combinatomers in the precursor GlcDG was kept unchanged in the product MGDG. Production of combinatomers resulting from exchange of hexose was minimal. This provides solid evidence of the epimerization of the glucose moiety of GlcDG, as well as the direct desaturation of acyl groups at the sn-1 position. PMID- 27653028 TI - Erratum. PMID- 27653029 TI - Muscle activation and energy expenditure of sedentary behavior alternatives in young and old adults. AB - The physiological mechanisms that underlie the metabolic benefits of breaking up sedentary behavior (SB) have yet to be determined. The purpose of this study is to compare energy expenditure (EE) and muscle activation (MA) responses to sitting and four SB alternatives in younger and older adults. Twenty-two adults, grouped by age (21-35 and 62-76 years), completed five randomly ordered 20 min tasks: (1) continuous sitting (Sit), (2) sitting on a stability ball (Ball), (3) continuous standing (Stand), (4) sitting interrupted by walking (S/W), and (5) sitting interrupted by standing (S/S). Muscle activation of two upper (trapezius and erector spinae) and two lower (rectus femoris and medial gastrocnemius) body muscles and total body EE were measured continuously. A linear mixed model using gender and age as a covariate with Bonferroni adjustment were used to determine significant differences between tasks. Collectively, S/W produced significantly higher MA and EE compared with Sit (p < 0.001). Stand and Ball provided significantly greater EE, but not MA, compared to Sit (p < 0.05), while S/S did not significantly change EE or MA compared to Sit. There were no net EE differences when comparing age groups across the tasks. Upper body MA was not consistent in both age groups across tasks. Specifically, during S/W the upper body MA of older adults (9.7 +/- 1.5% MVC) was double that of young adults (4.8 +/- 0.7% MVC, p = 0.006). Lower body MA responded similarly to all tasks in both age groups. Disrupting sitting with walking produced the largest increase in EE and MA compared to other SB alternatives in both age groups. These results are important considering the wide use of SB alternatives by researchers and public health practitioners. PMID- 27653030 TI - Adverse childhood experiences and autonomic regulation in response to acute stress: the role of the sympathetic and parasympathetic nervous systems. AB - BACKGROUND AND OBJECTIVES: After a previous report demonstrated blunted heart rate (HR) reactivity in association with adverse childhood experiences (ACEs) [Voellmin, A., Winzeler, K., Hug, E., Wilhelm, F. H., Schaefer, V., Gaab, J., ... Bader, K. (2015). Blunted endocrine and cardiovascular reactivity in young healthy women reporting a history of childhood adversity. Psychoneuroendocrinology, 51, 58-67. doi: 10.1016/j.psyneuen.2014.09.008 ], the present analysis aimed at clarifying the role of the sympathetic and parasympathetic branches of the autonomic nervous system in this relationship. DESIGN AND METHODS: One hundred eighteen healthy young women provided data on ACEs and underwent psychosocial stress testing. Systolic blood pressure (SBP) and respiratory sinus arrhythmia (RSA, quantified by high-frequency HR variability) were assessed as measures of sympathetic and parasympathetic cardiovascular activity, respectively. A mediation model was calculated to test the indirect effects of ACEs on HR via SBP and RSA. RESULTS: The effect of ACEs on HR reactivity was mediated by SBP reactivity but not by RSA reactivity. ACEs were associated with reduced SBP at rest. CONCLUSIONS: ACEs were associated with down regulation in a measure of sympathetic but no alteration in a measure of parasympathetic cardiovascular stress reactivity in adulthood. Future research will need to clarify whether this indicates risk or resilience. PMID- 27653031 TI - Relationship Between Different Subpopulations of Circulating CD4+ T-lymphocytes and Microvascular Structural Alterations in Humans. AB - BACKGROUND: Different components of the immune system, including innate and adaptive immunity (T-effector lymphocytes and T-regulatory lymphocytes-TREGs) may be involved in the development of hypertension. In addition, it was demonstrated in animal models that TREGs may prevent angiotensin II-induced hypertension and vascular injury/inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular structural alterations. METHODS: For this purpose, in the present study, we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and the media to lumen ratio (M/L) was calculated. In addition, retinal arteriolar structure was evaluated noninvasively by scanning laser Doppler flowmetry. Capillary density in the nailfold, dorsum of the finger, and forearm were evaluated by videomicroscopy. A peripheral blood sample was obtained before surgery for assessment of T-lymphocyte subpopulations by flow cytometry. RESULTS: Significant negative correlations were observed between indices of microvascular structure (M/L of subcutaneous small arteries and wall to lumen ratio of retinal arterioles) and circulating TREG lymphocytes. A direct correlation was observed between M/L of subcutaneous small arteries and circulating Th17 lymphocytes. In addition, total capillary density was correlated with a TREG effector memory subpopulation. CONCLUSION: Our data suggest that some lymphocyte subpopulations may be related to microvascular remodeling, confirming previous animal data, and opening therapeutic possibilities. PMID- 27653032 TI - Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum. AB - BACKGROUND: There is evidence of cerebral involvement among women with preeclampsia. Levels of the cerebral biomarkers neuron-specific enolase (NSE) and S100B are elevated during pregnancy in women developing preeclampsia. It is although not known if these biomarkers return to normal range postpartum. The aim with this study was to compare levels of S100B and NSE during pregnancy and 1 year postpartum in women who have had preeclampsia to women with normal pregnancies. METHODS: This study was a longitudinal study of cases (n = 53) with preeclampsia and controls (n = 58) consisted of normal pregnant women in matched gestational weeks. Plasma samples were collected at inclusion during pregnancy and 1 year postpartum. Plasma samples were analyzed for levels of S100B and NSE by enzyme-linked immunosorbent assays kits. RESULTS: Levels of NSE and S100B in women with preeclampsia were higher during pregnancy than in women with normal pregnancies. One year postpartum, women who have had preeclampsia still had a higher median level of both NSE (5.07 vs. 4.28 ug/l, P < 0.05) and S100B (0.07 vs. 0.06 ug/l, P < 0.05) compared to women with previous normal pregnancies. High levels of NSE and S100B postpartum remained associated with previous preeclampsia after adjustment for confounding factors. Levels of NSE correlated to S100B during pregnancy and postpartum. CONCLUSIONS: Levels of NSE and S100B are still elevated 1 year postpartum in women who have had preeclampsia in contrast to women with previous normal pregnancies. We hypothesize that there might be a persistent cerebral involvement among women with preeclampsia even 1 year postpartum. PMID- 27653033 TI - Effects of 17beta-Estradiol and Androgen on Glucose Metabolism in Skeletal Muscle. AB - Diabetes develops predominantly in males in experimental models, and extensive evidence suggests that 17beta-estradiol (E2) modulates progression of diabetes in humans. We previously developed a severely diabetic transgenic (Tg) mouse model by beta-cell-specific overexpression of inducible cAMP early repressor (ICER) and found that male ICER-Tg mice exhibit sustained severe hyperglycemia, but female ICER-Tg mice gradually became normoglycemic with aging. This implies that differences in circulating androgen and E2 levels might influence skeletal muscle glucose uptake and glycemic status. Here we examined whether a decrease of androgen or E2 excess can improve muscle glucose uptake in hyperglycemic male ICER-Tg mice and, conversely, whether a decrease of E2 or androgen excess can elevate blood glucose levels and impair muscle glucose uptake in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX) or ORX+E2 pellet implantation and normoglycemic female ICER-Tg mice with ovariectomy (OVX) or OVX+5alpha-DHT pellet implantation to alter the androgen to E2 ratio. ORX+E2 treatment of male ICER-Tg mice caused a rapid drop in blood glucose via both a dramatic increase of beta-cells and significantly improved muscle glucose uptake due to the induction of glucose transporter type 4 (GLUT4) expression and translocation of GLUT4 to the cell membrane. In contrast, OVX+5alpha-DHT-treated female ICER-Tg mice showed an elevation of blood glucose without any decrease of beta-cells; instead, they showed decreased muscle glucose uptake due to decreased activation of serine/threonine-specific protein kinase AKT and GLUT4 expression. These findings suggest that androgen (5alpha-DHT) promotes insulin resistance in females, whereas E2 improves insulin sensitivity in severely diabetic male mice. PMID- 27653035 TI - Maternal Obesity Programs Senescence Signaling and Glucose Metabolism in Osteo Progenitors From Rat and Human. AB - Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases, presumably via epigenetic mechanisms. However, evidence on the impact of gestational events on regulation of embryonic bone cell fate is sparse. We investigated the effects of maternal obesity on fetal osteoblast development in both rodents and humans. Female rats were fed control or an obesogenic high-fat diet (HFD) for 12 weeks and mated with male rats fed control diets, and respective maternal diets were continued during pregnancy. Embryonic rat osteogenic calvarial cells (EOCCs) were taken from gestational day 18.5 fetuses from control and HFD dams. EOCCs from HFD obese dams showed increases in p53/p21-mediated cell senescence signaling but decreased glucose metabolism. Decreased aerobic glycolysis in HFD-EOCCs was associated with decreased osteoblastic cell differentiation and proliferation. Umbilical cord human mesenchymal stem cells (MSCs) from 24 pregnant women (12 obese and 12 lean) along with placentas were collected upon delivery. The umbilical cord MSCs of obese mothers displayed less potential toward osteoblastogenesis and more towards adipogenesis. Human MSCs and placenta from obese mothers also exhibited increased cell senescence signaling, whereas MSCs showed decreased glucose metabolism and insulin resistance. Finally, we showed that overexpression of p53 linked increased cell senescence signaling and decreased glucose metabolism in fetal osteo-progenitors from obese rats and humans. These findings suggest programming of fetal preosteoblastic cell senescence signaling and glucose metabolism by maternal obesity. PMID- 27653034 TI - Administration of Melatonin and Metformin Prevents Deleterious Effects of Circadian Disruption and Obesity in Male Rats. AB - Circadian disruption and obesity synergize to predispose to development of type 2 diabetes mellitus (T2DM), signifying that therapeutic targeting of both circadian and metabolic dysfunctions should be considered as a potential treatment approach. To address this hypothesis, we studied rats concomitantly exposed to circadian disruption and diet-induced obesity (CDO), a rat model recently shown to recapitulate phenotypical aspects of obese T2DM (eg, circadian disruption, obesity, insulin resistance, and islet failure). CDO rats were subsequently treated daily (for 12 wk) by timed oral gavage with vehicle, melatonin (a known chronobiotic), metformin, or combination treatment of both therapeutics. Melatonin treatment alone improved circadian activity rhythms, attenuated induction of beta-cell failure, and enhanced glucose tolerance. Metformin alone did not modify circadian activity but enhanced insulin sensitivity and glucose tolerance. Importantly, the combination of melatonin and metformin had synergistic actions to modify progression of metabolic dysfunction in CDO rats through improved adiposity, circadian activity, insulin sensitivity, and islet cell failure. This study suggests that management of both circadian and metabolic dysfunctions should be considered as a potential preventative and therapeutic option for treatment of obesity and T2DM. PMID- 27653036 TI - Human Parturition Involves Phosphorylation of Progesterone Receptor-A at Serine 345 in Myometrial Cells. AB - The hypothesis that phosphorylation of progesterone receptor (PR) isoforms, PR-A and PR-B, in myometrial cells affects progesterone action in the context of human parturition was tested. Immunodetection of phosphoserine (pSer) PR forms in term myometrium revealed that the onset of labor is associated with increased phosphorylation of PR-A at serine-345 (pSer345-PRA) and that pSer345-PRA localized to the nucleus of myometrial cells. In explant cultures of term myometrium generation of pSer345-PRA was induced by interleukin-1beta and dependent on progesterone, suggesting that pSer345-PRA generation is induced by a proinflammatory stimulus. In the hTERT-HMA/B human myometrial cell line, abundance of pSer345-PRA was induced by progesterone in a dose- (EC50 ~1 nM) and time-dependent manner. Prevention of pSer345 (by site-directed mutagenesis) abolished the capacity for PR-A to inhibit anti-inflammatory actions of progesterone mediated by PR-B but had no effect on the transrepressive activity of PR-A at a canonical progesterone response element. Taken together, the data show that human parturition involves the phosphorylation of PR-A at serine-345 in myometrial cells and that this process is ligand dependent and induced by a proinflammatory stimulus. We also found that in myometrial cells, pSer345 activates the capacity for PR-A to inhibit antiinflammatory actions of progesterone mediated by PR-B. Phosphorylation of PR-A at serine-345 may be an important functional link between tissue-level inflammation and PR-A-mediated functional progesterone withdrawal to trigger parturition. PMID- 27653038 TI - A bilinear pairing based anonymous authentication scheme in wireless body area networks for mHealth. AB - Wireless body area networks (WBANs) have become one of the key components of mobile health (mHealth) which provides 24/7 health monitoring service and greatly improves the quality and efficiency of healthcare. However, users' concern about the security and privacy of their health information has become one of the major obstacles that impede the wide adoption of WBANs. Anonymous and unlinkable authentication is critical to protect the security and privacy of sensitive physiological information in transit from the client to the application provider. We first show that the anonymous authentication scheme of Wang and Zhang based on bilinear pairing is prone to client impersonation attack. Then, we propose an enhanced anonymous authentication scheme to remedy the flaw in Wang and Zhang's scheme. We give the security analysis to demonstrate that the enhanced scheme achieves the desired security features and withstands various known attacks. PMID- 27653037 TI - G6PC2 Modulates the Effects of Dexamethasone on Fasting Blood Glucose and Glucose Tolerance. AB - The glucose-6-phosphatase catalytic subunit 2 (G6PC2) gene encodes an islet specific glucose-6-phosphatase catalytic subunit. G6PC2 forms a substrate cycle with glucokinase that determines the glucose sensitivity of insulin secretion. Consequently, deletion of G6pc2 lowers fasting blood glucose (FBG) without affecting fasting plasma insulin. Although chronic elevation of FBG is detrimental to health, glucocorticoids induce G6PC2 expression, suggesting that G6PC2 evolved to transiently modulate FBG under conditions of glucocorticoid related stress. We show, using competition and mutagenesis experiments, that the synthetic glucocorticoid dexamethasone (Dex) induces G6PC2 promoter activity through a mechanism involving displacement of the islet-enriched transcription factor MafA by the glucocorticoid receptor. The induction of G6PC2 promoter activity by Dex is modulated by a single nucleotide polymorphism, previously linked to altered FBG in humans, that affects FOXA2 binding. A 5-day repeated injection paradigm was used to examine the chronic effect of Dex on FBG and glucose tolerance in wild-type (WT) and G6pc2 knockout mice. Acute Dex treatment only induces G6pc2 expression in 129SvEv but not C57BL/6J mice, but this chronic treatment induced G6pc2 expression in both. In 6-hour fasted C57BL/6J WT mice, Dex treatment lowered FBG and improved glucose tolerance, with G6pc2 deletion exacerbating the decrease in FBG and enhancing the improvement in glucose tolerance. In contrast, in 24-hour fasted C57BL/6J WT mice, Dex treatment raised FBG but still improved glucose tolerance, with G6pc2 deletion limiting the increase in FBG and enhancing the improvement in glucose tolerance. These observations demonstrate that G6pc2 modulates the complex effects of Dex on both FBG and glucose tolerance. PMID- 27653039 TI - Secured Medical Images - a Chaotic Pixel Scrambling Approach. AB - In this paper, a cryptosystem is proposed to encrypt 16-bit monochrome DICOM image using enhanced chaotic economic map. A new enhanced chaotic economic map (ECEM) is designed from the chaotic economic map which has better bifurcation nature and positive Lyapunov exponent values. In order to improve the sternness of the encryption algorithm, the enhanced chaotic map is employed to generate the pixel permutation, masking, and swapping sequences. The substitution operation is introduced in-between the standard permutation and diffusion operations. The robustness of the proposed image encryption algorithm is measured by various analyses such as histogram, key sensitivity, key space, number of pixel change rate (NPCR), unified average change intensity (UACI), information entropy and correlation coefficient. The results of the security analyses are compared with existing algorithms to validate that the proposed algorithm is better in terms of larger key space to resist brute force attacks and other common attacks on encryption. PMID- 27653040 TI - A Secure Dynamic Identity and Chaotic Maps Based User Authentication and Key Agreement Scheme for e-Healthcare Systems. AB - Secure user authentication schemes in many e-Healthcare applications try to prevent unauthorized users from intruding the e-Healthcare systems and a remote user and a medical server can establish session keys for securing the subsequent communications. However, many schemes does not mask the users' identity information while constructing a login session between two or more parties, even though personal privacy of users is a significant topic for e-Healthcare systems. In order to preserve personal privacy of users, dynamic identity based authentication schemes are hiding user's real identity during the process of network communications and only the medical server knows login user's identity. In addition, most of the existing dynamic identity based authentication schemes ignore the inputs verification during login condition and this flaw may subject to inefficiency in the case of incorrect inputs in the login phase. Regarding the use of secure authentication mechanisms for e-Healthcare systems, this paper presents a new dynamic identity and chaotic maps based authentication scheme and a secure data protection approach is employed in every session to prevent illegal intrusions. The proposed scheme can not only quickly detect incorrect inputs during the phases of login and password change but also can invalidate the future use of a lost/stolen smart card. Compared the functionality and efficiency with other authentication schemes recently, the proposed scheme satisfies desirable security attributes and maintains acceptable efficiency in terms of the computational overheads for e-Healthcare systems. PMID- 27653041 TI - Simulation of Trauma Incidents : Modelling the Evolution of Patients and Resources. AB - Mathematical modeling and simulation with medical applications has gained much interest in the last few years, mainly due to the widespread availability of low cost technology and computational power. This paper presents an integrated platform for the in-silico simulation of trauma incidents, based on a suite of interacting mathematical models. The models cover the generation of a scenario for an incident, a model of physiological evolution of the affected individuals, including the possible effect of the treatment, and a model of evolution in time of the required medical resources. The problem of optimal resource allocation is also investigated. Model parameters have been identified according to the expertise of medical doctors and by reviewing some related literature. The models have been implemented and exposed as web services, while some software clients have been built for the purpose of testing. Due to its extendability, our integrated platform highlights the potential of model-based simulation in different health-related fields, such as emergency medicine and personal health systems. Modifications of the models are already being used in the context of two funded projects, aiming at evaluating the response of health systems to major incidents with and without model-based decision support. PMID- 27653042 TI - Fine-grained Database Field Search Using Attribute-Based Encryption for E Healthcare Clouds. AB - An effectively designed e-healthcare system can significantly enhance the quality of access and experience of healthcare users, including facilitating medical and healthcare providers in ensuring a smooth delivery of services. Ensuring the security of patients' electronic health records (EHRs) in the e-healthcare system is an active research area. EHRs may be outsourced to a third-party, such as a community healthcare cloud service provider for storage due to cost-saving measures. Generally, encrypting the EHRs when they are stored in the system (i.e. data-at-rest) or prior to outsourcing the data is used to ensure data confidentiality. Searchable encryption (SE) scheme is a promising technique that can ensure the protection of private information without compromising on performance. In this paper, we propose a novel framework for controlling access to EHRs stored in semi-trusted cloud servers (e.g. a private cloud or a community cloud). To achieve fine-grained access control for EHRs, we leverage the ciphertext-policy attribute-based encryption (CP-ABE) technique to encrypt tables published by hospitals, including patients' EHRs, and the table is stored in the database with the primary key being the patient's unique identity. Our framework can enable different users with different privileges to search on different database fields. Differ from previous attempts to secure outsourcing of data, we emphasize the control of the searches of the fields within the database. We demonstrate the utility of the scheme by evaluating the scheme using datasets from the University of California, Irvine. PMID- 27653043 TI - On-line monitoring of electrolytes in hemodialysis: on the road towards individualizing treatment. AB - INTRODUCTION: End-stage renal disease (ESRD) patients depend on dialysis for removal of toxic waste products, fluid overload relief and maintenance of electrolyte balance. Dialysis prolongs millions of lives. To some extent, ESRD has become a manageable disease with a steadily growing dialysis population of increasing average age and associated comorbidity. During 7 decades many technical refinements have been developed e.g. sodium profiling, blood volume, ultrafiltration variation based on blood pressure measurement, urea kinetics etc. Despite its large potentials, in-line electrolyte monitoring lags behind in dialysis treatment. Areas covered: In this paper, we review the state of technologies available for in-line monitoring of the electrolytes sodium, potassium and calcium during hemodialysis. Expert commentary: We concluded that individual optimization of dialysate composition should be able to improve hard medical outcomes, but practical clinical implementation stands/falls with reliable and affordable in-line ion-selective sensing technology. Optical ion selective microsensors and microsystems form a promising pathway for individualizing the dialysis treatment. PMID- 27653044 TI - Arterial stiffness is not increased in patients with short duration rheumatoid arthritis and ankylosing spondylitis. AB - Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is an independent predictor of CV events. The aim of the study was to assess arterial stiffness and inflammatory markers in patients with short duration chronic arthritis. We assessed carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), traditional CV risk factors and inflammatory and endothelial markers in 71 chronic arthritis patients (RA and AS) and in 29 healthy controls. We did not find differences in PWV (for RA, AS and controls, respectively: 10 [8.8-10.9] versus 10.7 [9.1-11.8] versus 9.2 [8.3-11.4] m/s; p = .14) and AIx (for RA, AS and controls, respectively: 24.3 +/- 11.5 versus 5.7 +/- 12.4 versus 10 +/- 12.8%; p = .22). Both groups of arthritis patients had active disease with significantly elevated inflammatory markers compared to controls. There were no correlations between endothelial and inflammatory markers and parameters of arterial stiffness in arthritis patients. When analyzing arthritis patients according to median of PVW, there were no significant differences in inflammatory and endothelial markers. We found that in patients with short duration active RA and AS arterial stiffness was not increased and furthermore, there was no association between markers of systemic inflammation and arterial stiffness. PMID- 27653045 TI - Performance of Bemisia tabaci Biotype B on Soybean Genotypes. AB - Bemisia tabaci (Genn.) (Hemiptera: Aleyrodidae) has been recognized as an important pest of many agricultural systems including soybean [Glycine max (L.) Merrill] crops. As an alternative to chemical control, the use of resistant genotypes represents an important tool for integrated pest management (IPM). This study aimed to evaluate the biological development of Bemisia tabaci biotype B confined on 13 soybean genotypes under greenhouse conditions. Initially, the nymphal period, complete development period (egg-adult), and the viability of the silverleaf whitefly nymphs were evaluated in all genotypes. Then, four genotypes promising for resistance ('Jackson,' UX-2569-159, 'P98Y11,' and 'TMG132 RR') and a susceptible genotype (PI-227687) were selected for further assays, where two insect populations were compared: a first population from the initial rearing (cabbage plants) and another corresponding to insects previously reared out on the selected genotypes. In addition to the parameters evaluated in preliminary tests, we also determined the viability and incubation period of eggs. Moderate levels of resistance (antibiosis/antixenosis) to B. tabaci biotype B were found in three genotypes. 'P98Y11' and 'TMG132 RR' were less suitable for insect development, extending the development cycle, and UX-2569-159 caused high nymphal mortality. We did not observe a significant increase in the level of plant resistance by the use of previously stressed insects. This suggests that the evaluation of a single whitefly generation may be sufficient to make correct decisions on promising soybean genotypes. PMID- 27653047 TI - The Mais Medicos (More Doctors) Program: assessments and prospects. PMID- 27653046 TI - Pharmacological inhibitors of TRPV4 channels reduce cytokine production, restore endothelial function and increase survival in septic mice. AB - Sepsis is characterized by systemic inflammation, edema formation and hypo perfusion leading to organ dysfunction and ultimately death. Activation of the transient receptor potential vanilloid type 4 (TRPV4) channel is associated with edema formation and circulatory collapse. Here, we show that TRPV4 channels are involved in the hyper-inflammatory response and mortality associated with sepsis. Pharmacological inhibition of TRPV4 channels in mice reduced mortality in lipopolysaccharide and cecal-ligation-and-puncture models of sepsis, but not in a tumor necrosis factor-alpha (TNFalpha)-induced sepsis model. These protective effects of TRPV4 channel inhibition were attributable to prevention of the sepsis induced surge of a broad spectrum of pro-inflammatory cytokines, including TNFalpha, interleukin (IL)-1 and IL-6, and subsequent preservation of endothelial cell function, including Ca2+ signaling, integrity and endothelium-dependent vasodilation. These results suggest that TRPV4 antagonists may be of therapeutic utility in the management of sepsis. PMID- 27653048 TI - Primary care in Brazil, and the Mais Medicos (More Doctors) Program in the Unified Health System: achievements and limits. AB - An historical analysis of Brazil's policies in Primary Healthcare, with emphasis on the Family Health Strategy (FHS), and the Mais Medicos Program (PMM). Studies were made of documents and secondary official data, and the bibliography that has been produced on this theme. It was found that primary healthcare has been established and successfully consolidated as an option in healthcare for a great part of the population of Brazil. There have, however, been structural hurdles, which have tended to compromise the effectiveness and sustainability of this policy. It was identified that these obstacles arise principally from insufficient financing and from inefficient modes of planning and management. The Mais Medicos Program has widened care coverage and made the distribution of primary healthcare doctors more equitable, although it has not resolved the structural problems of the public system. PMID- 27653049 TI - Beyond the Mais Medicos (More Doctors) Program. PMID- 27653050 TI - Family and Community Medicine: now more than ever! PMID- 27653051 TI - Some risks connected with medical training in the Mais Medicos (More Doctors) Program. PMID- 27653052 TI - Where now for the Mais Medicos (More Doctors) Program? PMID- 27653053 TI - Impact of the Mais Medicos (More Doctors) Program in reducing physician shortage in Brazilian Primary Healthcare. AB - The Mais Medicos (More Doctors) Program (PMM) was put in place in Brazil aiming to reduce inequalities in access to Primary Healthcare. Based on diverse evidence that pointed to a scenario of profound shortage of doctors in the country, one of its central thrusts was emergency provision of these professionals in vulnerable areas, referred to as the Mais Medicos para o Brasil (More Doctors for Brazil) Project. The article analyses the impact of the PMM in reducing shortage of physicians in Brazilian municipalities. To do this, it uses the Primary Healthcare Physicians Shortage Index, which identifies and measures the shortage in the periods of March 2003 and September 2015, before and after implementation of the program. The results show that there was a substantial increase in the supply of physicians in primary healthcare in the period, which helped reduce the number of municipalities with shortage from 1,200 to 777. This impact also helped reduce inequalities between municipalities, but the inequities in distribution persisted. It was also found that there was a reduction in the regular supply of doctors made by municipalities, suggesting that these were being simply substituted by the supply coming from the program. Thus, an overall situation of insecurity in care persists, reflecting the dependence of municipalities on the physician supply from the federal government. PMID- 27653054 TI - Primary Health Care in Brazil and the Mais Medicos (More Doctors) Program: an analysis of production indicators. AB - This study analyzes the number of medical appointments and referrals performed in primary health care in Brazil focusing on the Mais Medicos Program (More Doctors Program). It is a cross-sectional study on the work of physicians included, or not, to the Mais Medicos Program in 2014. Based on validation protocols, a unified database was created from two health information system databases - SIAB and ESUS. Absolute indicators were defined: the total of medical appointments per month; medical referrals and community health education activities. In addition, other indicators were considered, such as weekly rates and productivity of appointments, in line with the profile of Brazilian municipalities. The mean of all appointments was 285 per month corresponding to an average of 14.4 appointments/day. In the poorest municipalities, the figures for the Mais Medicos Program physicians were higher than national rates. The educational activities provided by primary care teams that included a Mais Medicos Program professional were higher in Brazilian capital cities. The Mais Medicos Program achieved one of its main goals, which was to increase health access for vulnerable populations and to contribute towards the consolidation of primary health care in Brazil. PMID- 27653055 TI - Emergency supply of doctors by the Mais Medicos (More Doctors) Program and the quality of the structure of primary health care facilities. AB - The health policy context in Brazil has featured a series of measures to improve primary health care (PHC), including a national access and quality improvement program (Programa Nacional de Melhoria do Acesso e Qualidade, PMAQ-AB) and the Mais Medicos Program (More Doctors, PMM) and upgrading PHC centers ('Requalifica UBS'). The paper examines the PMM's placement of doctors, by quality of PHC structure, in an endeavor to identify synergies among the three programs. It reports on a transverse study based on secondary data from PMAQ-AB Cycles 1 and 2, the PMM and 'Requalifica UBS'. The PHC facilities inventoried during PMAQ-AB Cycle 1 were classified, on pre-established typology, into five groups ranked from A (best) to E (failed). They were then compared in terms of PMM personnel allocated and Requalifica UBS proposals. The results point to convergences in investments by the three programs. Incentives targeted predominantly PHC facilities of types B and C, indicating a concentration of efforts on PHC facilities with potential for structural quality improvements. In addition to expanding access, the provision of doctors by the PMM, added to infrastructure upgrades and work process improvements, contributes to addressing high turnover and guaranteeing retention of doctors in PHC. PMID- 27653056 TI - The Mais Medicos (More Doctors) Program, the infrastructure of Primary Health Units and the Municipal Human Development Index. AB - The main objective of this article was to examine the context in which professionals working within the Mais Medicos (More Doctors) Program operate. This study used the infrastructure scale of primary health units (PHUs), which was recently developed by Soares Neto and colleagues to provide more information regarding the relationship between the infrastructure of PHUs and the Municipal Human Development Index (MHDI) of municipalities that received Mais Medicos Program doctors. Using exploratory and inferential statistics, the article shows that 65.2% of the PHUs that received Mais Medicos Program doctors had medium quality infrastructure and only 5.8% of them had low-quality infrastructure. The correlation of 0.50 between the infrastructure indicator and the MHDI points to a moderate tendency for municipalities with low MHDIs to have more precarious PHUs. Using multiple linear regression analysis it can be inferred that the main factor that contributed to the increase in the infrastructure indicator of the PHUs was the average municipal income. On the other hand, the factor that negatively affected the infrastructure of the PHUs was being located in the north or northeast regions. PMID- 27653057 TI - The Mais Medicos (More Doctors) Program: the placement of physicians in priority municipalities in Brazil from 2013 to 2014. AB - The inadequate placement and distribution of health professionals are problems that occur in various countries. The scope of the "Programa Mais Medicos" (More Doctors Program) was to reduce the shortfall of physicians and diminish regional inequalities in health. A descriptive study on the placement of physicians between 2013 and 2014 using the Ministry of Health database is presented. There was an allocation of 14,168 physicians to the 3,785 municipalities that signed up to the program: 2,377 met the priority and/or vulnerability criteria and received 77.7% of the physicians; 1,408 received 22.3% of the physicians, but did not meet the established priorities. This study reveals the reduction in the lack of physicians, mainly in the North and Northeast. These regions account for 36% of the Brazilian population and 46.3% of the physicians were allocated there. However, the introduction of an eligibility profile, which allocated 3,166 physicians in 1,408 non-priority municipalities is questionable. The conclusion drawn is that this may have hindered the ability of the Mais Medicos Program to fully achieve its objectives as a public policy aimed at reducing regional inequalities of access to primary healthcare. Further studies are necessary to evaluate the impact of the Mais Medicos Program. PMID- 27653058 TI - The implementation of the Mais Medicos (More Doctors) Program and comprehensiveness of care in the Family Health Strategy. AB - The Mais Medicos (More Doctors) Program is a Brazilian government program that aims to expand access to medical care and thus improve the quality of primary healthcare delivery. This study aims to analyze the perceptions of nondoctor members of the Family Health Strategy teams regarding comprehensiveness of care after the inclusion of doctors from the program. The study encompassed 32 poor municipalities in Brazil's five geographical regions. A total of 78 health workers were interviewed. The interviews were transcribed and analyzed using content analysis and the software Atlas.ti Version 1.0.36. The study found that the program led to: an increase in access to and accessibility of services provided under the Family Health Strategy; humanized care and the establishment of bonds - understanding, partnership, friendship and respect; going back to clinical approaches - dedicated time, listening attentively, and detailed physical examination; the desire and willingness to resolve problems; continuity of care; guarenteeing home visits; and coordination of multidisciplinary teams in networks. It was concluded that the Mais Medicos Program contributed to the enhancement of comprehensiveness, thus leading to improvements in primary health care delivery. PMID- 27653059 TI - Assessment of the scope of practice of physicians participating in the Mais Medicos (More Doctors) Program, and associated factors. AB - The purpose of this study was to characterize the scope of practice of physicians working in primary healthcare participating in the Mais Medicos (More Doctors) Program ('PMM') and investigate the factors associated with execution of a larger number of clinical activities. It is an exploratory study carried over January to March 2016, through a self-applied questionnaire containing a list of 49 procedures, activities and actions carried out in primary healthcare. A total of 1,241 physicians took part in the study, most of them female, between age 40 and 49, and of Cuban nationality. The physicians carried out an average of 22.8 +/- 8.2 procedures; they reported knowing how to carry out a larger number of procedures. Factors associated with executing a larger number of procedures were: being male, having graduated more recently, two years or less practicing in their primary healthcare unit, practicing in the North or South geographical regions, in small towns and more distant from the regional health headquarters. The main reason for not carrying out the procedures and activities that they reported knowing how to do was the lack of materials and inadequate infrastructure. The results show that the scope of practice of the physicians of the PMM is lower than their capacities, and that interventions with the intention of widening their scope are necessary. PMID- 27653060 TI - Evaluation of user satisfaction and service responsiveness in municipalities enrolled in the Mais Medicos (More Doctors) Program. AB - The Mais Medicos (More Doctors) Program (PMM) addresses shortages of doctors, one of whose objectives is to reduce regional inequalities in access to health care. This descriptive cross-sectional study evaluated service responsiveness and user satisfaction with PMM doctors among 263 users of the public health system in 32 municipalities with 20% or more of extreme poverty. Questionnaires of open and closed questions were used. Users were satisfied with patient-doctor relationships, information about diseases and treatment and the clarity and comprehensibility of medical indications. The doctors' technical and humanised conduct helped ensure satisfaction among users, who stressed the importance of the programme's continuance. As regards responsiveness, most users were pleased with the non-medical aspects of care: prompt scheduling of appointments, waiting times of less than one hour and privacy. Users suggested improving infrastructure and making more medicines and more doctors available, which should be considered by SUS managers to help ensure access to the right to health guaranteed in Brazil's constitution. PMID- 27653061 TI - Analysis of the Mais Medicos (More Doctors) Program in terms of its institutional arrangements: sector cooperation, federative relations, social participations and territoriality. AB - This article analyzes the Mais Medicos (More Doctors) program based on the concept of an institutional arrangement, understood as the set of rules, organizations and processes that define the specific design of a given public policy, defining how it will articulate across players and interests. This concept will allow us to understand the dynamics of the players in this arrangement, as well as their governance, decision-making and governability, and how these factors reflect on public policy performance. A deeper analysis is based on four categories considered essential to understand an organizational arrangement in Brazil: sector cooperation (sometimes referred to as intersecoriality), federative relationships, social involvement and territoriality. PMID- 27653062 TI - Mais Medicos (More Doctors) Program: its contribution in view of WHO recommendations for provision of doctors. AB - In order to examine whether Brazil's Mais Medicos (More Doctors) Programme (PMM) reflected World Health Organisation (WHO) recommendations for improved attraction, retention and recruitment of health workers in remote and rural areas, this descriptive, qualitative study drew on document analysis in order to compare the WHO recommendations published in 2010 with Brazil's Law No. 12,871/13, which instituted the PMM. Of the 16 WHO recommendations systematised here, the PMM met 37.5%. Recommendations not incorporated into the PMM include career development programmes and public recognition strategies. Although reflecting WHO recommendations and already in place elsewhere in the SUS prior to announcement of the PMM, the National Retention Grant Programme and multi professional teams (as in the Family Health Strategy) were not implemented by the PMM. The programme contains innovative components such as a new curriculum for medical schools and compulsory medical service. On the other hand, the PMM could have invested more in personal and professional support. PMID- 27653063 TI - The Mais Medicos (More Doctors) Program: panorama of the scientific output. AB - Despite the progress achieved by the Primary Health Care and Family Health Strategy in the Unified Health System (SUS) challenges still remain with regard to the universality of access and the quality of services, one of the factors being the unequal distribution of physicians. The Brazilian Government established the Mais Medicos Program (More Doctors Program), in order to move forward in the provision, placement and training of physicians in the SUS. This study consists of a review of the literature of the Mais Medicos Program, in order to map and assess the scientific production on the Program, as well as summarize the findings and present the results of the analysis. Fifty-four publications were selected, which evaluate the Program in terms of effectiveness, analysis of the implementation process, the media and the statements of the actors and assessment of the legal and constitutional precepts. The criticisms and limitations found were also systematically analyzed. With respect to the analysis, evaluations of the Program are overwhelmingly positive, showing important changes in the work processes in services and training. The studies that show the Program as being an important instrument for the effective implementation of the right to health are highlighted. PMID- 27653064 TI - Academic tutorship of the Mais Medicos para o Brasil (More Doctors to Brazil) Project in Santa Catarina: the ethical-political viewpoint. AB - This study aims to identify the fundamentals that drive the academic tutorship of the Mais Medicos para o Brasil (More Doctors for Brazil) project in Santa Catarina, based on the unit of analysis entitled values achieved. It is an exploratory and comprehensive study carried out in 2015, with tutors of the State of Santa Catarina, decentralized reference professionals of the Education and Health Ministries, and key reference professionals of the Education Ministry. Focus groups were used as the instrument for collection of data, through semi structured interview. Based on the category Emergency care as a force of innovation in the Mais Medicos Program, the analysis was conducted from an ethical-political approach. Three fundamentals emerged: 'Putting out fires', 'Qualification of the Project', and 'the procedural point of view'. It was concluded that academic tutorship of the productive activities of doctors in emergency care is not an isolated pedagogical approach, since it is a part and a consequence of the historic development of the theory and of the practice. The activity corresponds, dialectically, to movements of rupture, resistance, emancipation and also requires collective reflection about the values chosen and achieved in the acts of decision. PMID- 27653065 TI - Physicians' reflections on the personal learning process and the significance of distance learning in family health. AB - The scope of the article is to present the reflections of professionals from the Mais Medicos Program (More Doctors Program) on the significance of the specialization course in Family Health in terms of professional practice and learning the most important concepts. This is an empirically based qualitative study on the statements recorded in the "Critical reflection on their personal learning process" of the final work of the specialization course at the Federal University of Pelotas. For textual analysis, 101 reports were randomly selected from a total of 1,011 reports completed in seven states of the North, Northeast and South of Brazil from June to December 2015. The initial barriers were overcome with tutor support and team integration, with emphasis on teaching tools for the improvement of clinical practice and strategic organization of work and greater understanding of the public health system. Fostering the learning of the Portuguese language and the exchange of experience in the forums were considered valuable positive aspects. Despite the difficulty in Internet access in some municipalities it reaffirmed the central role of ongoing education and the viability of the problem-solving methodology, even from a distance. PMID- 27653066 TI - The Mais Medicos (More Doctors) Program in Northeast: evaluation of hospitalizations for Primary Healthcare-sensitive conditions. AB - This paper analyzes the increase in professionals in Brazil's Northeastern Region resulting from the Mais Medicos (More Doctors) Program. The scale of the increase was analyzed through the indicator Hospitalizations for Primary-Care Sensitive Conditions (HPSCs). The method used was a quantitative approach, based on data on distribution of doctors and service they provided in these states, and on hospitalizations for diarrhea and gastroenteritis in the period September 2012 to August 2015. The choice of this condition took into account the aspects of: its high frequency in the period; the simplicity of intervention; and its historic occurrence in the Northeast. The results show that the Mais Medicos Program had an influence on the reduction of hospitalizations for this type of condition - they fell by 35% in the period investigated, with important differences between the states. In spite of the significant scale of the entry of medical professionals into the health system, it is known that in isolation simply increasing the number of professionals of a particular type has a limited effect in improving primary healthcare. PMID- 27653067 TI - Analysis of the experience of Cuban physicians in a Brazilian metropolis in accordance with the Paideia Method. AB - We had hoped that the Mais Medicos Program (More Doctors Program) would have generated several changes and reflections in each municipality in which it was deployed. In order to observe those changes, we sought to analyze the experience of Cuban physicians in the Mais Medicos program from an actor-centered perspective, based on the Paideia Method - an approach that seeks to enhance the ability of the subjects to analyze and intervene in their practice. We performed semi-structured interviews to analyze our research object that consisted in the experience of those actors included professionally in the Mais Medicos program in a metropolis with unique characteristics. In order to assess the interviews, we applied Content Analysis followed by Thematic Analysis. From the discourse of the actors, of which illustrative excerpts are transcribed in this article, we can affirm that the program's potential surpassed any initial barriers, presenting itself as fine-tuning instrument for replacing the biomedical model in line with the Paideia Method. PMID- 27653068 TI - A comparative analysis of the implementation of the Mais Medicos (More Doctors) Program in municipalities in the State of Rio Grande do Sul, Brazil. AB - The Mais Medicos (More Doctors) Program has led to an increase in the number of doctors and medical treatment in primary health care services across Brazil. This article presents the results of a case-control study of groups of municipalities based on secondary data sources. It aims to explore and discuss a set of indicators of primary health care service delivery. An improvement in performance against structural indicators was observed in municipalities where the program was implemented. With respect to the outcome indicators, a slight improvement in service delivery was observed in municipalities where the program was implemented. However, no difference was observed in impacts between the case and control municipalities. These results may have been influenced by the fact that the program has only been underway for a limited time, by underreporting of doctors by the National Health Facilities Register (CNES, acronym in Portuguese), and the predominantly substitutive nature of the allocation of medical professionals under the program in the selected municipalities. PMID- 27653069 TI - Effectiveness of the Family Health Strategy in units with, and without, the Mais Medicos (More Doctors) Program in a municipality in the west of Parana state, Brazil. AB - Two years after the Mais Medicos (More Doctors) Program, (Programa Mais Medicos - PMM) was put in place in Brazil, there is a need to study its feasibility. This study aims to evaluate the effectiveness of the primary healthcare service offered, from the point of view of the health professionals, comparing units which have, and which do not have, doctors from the Mais Medicos Program. It is a quantitative survey, using for data collection the instrument Primary Care Assessment Tool - Brazil, Version for Health Professionals, applied across the totality of the family health units in a medium sized municipality in the interior of the southern Brazilian State of Parana, from November 2015 to February 2016. It covered 72 professionals, 47 of them allocated in Family Health Strategy (FHS) units and 25 in FHS units containing the Program. In both groups the scores for core attributes (6.93) and general attributes (7.10) were considered to be appropriate to the precepts of primary healthcare. However, the attributes accessibility (4.17), in both groups, and coordination - information system (6.57), in units with the Mais Medicos Program, did not reach the satisfactory level, indicating a need to alter the organization of the Family Health Strategy, whether the PMM program is implemented or not. PMID- 27653070 TI - Service users' perceptions of the Mais Medicos (More Doctors) Program in the Municipality of Mossoro, Brazil. AB - The Mais Medicos (More Doctors) Program (MMP), which was launched in 2013, sought to provide doctors to work in primary health care in priority areas within the Brazilian Unified Health System (SUS). This article analyzes the perception of MMP service users through the results of a qualitative study that consisted of interviews with service users of the Family Health Strategy (ESF) in which doctors from the MMP worked. The service users who were interviewed had a positive view of the MMP because it had expanded access to health care, although there still remained organizational and technical problems that limited the use of services. The performance of foreign doctors was well viewed, with an emphasis on a humanized relationship between doctor and service user, which was characterized by listening, attention and dialogue. In terms of communication with these professionals, some service users referred to language as being a barrier, which was ameliorated by the use of communication strategies within the ESF. The MMP offered a quick and satisfactory resolution to the historical problem of difficulty of access to doctors in Brazil. However, the effectiveness of the Brazilian health system requires that weaknesses are overcome, such as access to specialized services, organizational problems and the implementation of service production models that are centered on illness. PMID- 27653071 TI - Strengthening Primary Health Care in the municipalities in the Metropolitan Region of Porto Alegre, Brazil, after the introduction of the Mais Medicos (More Doctors) Program: an inter-municipal comparison. AB - This article aims to propose an adaptation of the methodology used by Starfield and Shy (2002) to assess the quality of health care in the municipalities which joined the Mais Medicos (More Doctors) Program. The indicators were adapted for each one of the nine criteria proposed in the methodology and were applied to medium and large municipalities in the Metropolitan Region of Porto Alegre before and after they were integrated in the Mais Medicos Program. In 2014, the municipalities were grouped into three groups according to their scores. An analysis concerning any correlations between the different group scores for the municipalities and the health indicators that were evaluated, did not reveal anything significant. However the averages of the evaluated indicators were better in the group of municipalities characterized through having the best APS scores. In relation to the income indicator, the highest amount of money spent per capita in health is related to the best APS performance in the municipalities. An adaption of this methodology may be able to provide a better understanding of the policies related to health care. PMID- 27653072 TI - The Mais Medicos (More Doctors) Program in Mato Grosso State, Brazil: implementation analysis. AB - Although the 224 health professionals engaged by the More Doctors for Brazil Project (Projeto Mais Medicos para o Brazil, PMMB) to strengthen the National Primary Health Care Policy (Politica Nacional de Atencao Basica, PNab) in 104 municipalities of Mato Grosso (MT) State have encountered significant problems in the work process, important advances have resulted in the health of populations served by the More Doctors Programme (Programa Mais Medicos, PMM). This article analyses the implementation and development of the PMM in MT, from 2013 to 2015, on the basis of primary data from focus groups and interviews of social stakeholders at the institutions involved and secondary data from reports by supervisors, tutors, managers and institutions on the MT State Coordinating Committee (CCE) of the PMM. Despite political difficulties in managing implementation, the results show that the endeavour was beneficial in that it surmounted previous obstacles, afforded users greater access, prompted discussion of the problem and proposed and experimented with ways to strengthen primary health care. We conclude that there is a need for broader academic discussion of the provision and training of doctors, of the model of care and of human resource capacity-building by continuing professional development with integration among teaching, service and community. PMID- 27653073 TI - Characteristics of the distribution of doctors in the Mais Medicos (More Doctors) Program in the states of Brazil's Northeast. AB - Inequalities in access to health, reflecting shortages and inadequate geographical distribution of health professionals, have been indicated as a challenge for Brazil. This paper analyzes the geographical distribution of professionals of the Mais Medicos Program allocated in the Northeastern Region of Brazil, through a descriptive cross-sectional study. Secondary data provided by the Health Ministry were used, and thematic maps of distribution of doctors in the Region were prepared. Data on 4,716 doctors who became members of health teams in 1,294 municipalities in six Indigenous Health Districts in the years 2013 and 2014 were analyzed. The greater part of the municipalities of the Region received between one and five doctors. The municipalities most benefited had, at least, 20% of their population in extreme poverty. 99.9% of the doctors were allocated in a Health Center or Primary Healthcare Unit. The majority were women (57%), predominantly of the 45-49 age group (24%). In spite of the advances achieved by the Program - such as distribution of the doctors in locations with greater vulnerability - some States continue to have significant shortages of healthcare. PMID- 27653074 TI - Expanding health access in the more vulnerable region in the state of Sao Paulo, Brazil: is this a reflection of the Mais Medicos (More Doctors) Program? AB - The Mais Medicos (More Doctors) Program seeks to broaden access to health by providing medical professionals, investments in health units and multi professional integration geared to the Family Health Strategy. Vale do Ribeira includes 25 cities and is among the most vulnerable regions in Sao Paulo. It has been allocated 41 physicians from the Program. This study is to evaluate access to health, comparing health indicators before and after the Program. We collected data from DATASUS, SIAB, and the Ministry of Health. There was a marked increase in the number of appointments for infants under one year of age, adults, the elderly, STD/HIV patients and group patient care. There was a decrease in appointments outside the catchment area, as well as hospital admissions for other causes, mothers exclusively breastfeeding their infants up to four months. We concluded that after deployment of the Program, there was an increase in health access and health promotion focused on an area that presents an enormous challenge for Primary Health Care (PHC). It would seem that, since this is a high vulnerability area with a large area for care, hospital admissions for PHC care sensitive conditions, as well as referrals for secondary services, did not decrease. PMID- 27653075 TI - Participation of small municipalities in the Mais Medicos para o Brasil (More Doctors to Brazil) Program in the macro-region of Northern Parana. AB - Doctor shortage is a constant problem in smaller cities and towns, which tend to be more vulnerable from a social and economic point of view, and located in geographically isolated areas. The goal of this study was to establish the share and characteristics of the small cities and towns in the macro-region of northern Parana that subscribed to the Mais Medicos para o Brasil (PMMB) program. This is a quantitative study of 82 cities and towns using primary and secondary data. Results show that only a few of them (6.1%) had any adherence criteria, which was not an impediment for other cities and towns (75%) to adhere to the project. Cities and towns with over five thousand inhabitants, lower municipal HDI (Human Development Index), some adherence criteria and more geographically isolated, either from the main city in the region or the closest large or mid-sized city, tended to adhere to the PMMB. It is undeniable that the PMMB significantly reduced the uneven distribution of doctors in Brazil and the study region. However, the sustainability of this policy is linked to addressing other remaining challenges in the SUS system. PMID- 27653076 TI - Interview: Evaluating the impact of the of the Mais Medicos (More Doctors) Program: how can we measure outcomes? PMID- 27653077 TI - Mais Medicos (More Doctors) Program - a view from England. AB - The Programa Mais Medicos (PMM) is a national strategy to increase the numbers of Brazilian trained doctors entering primary care and is possibly the most significant human resource intervention in Latin America in recent years. From an English perspective, there are clearly opportunities to learn the PMM. First, PAHO's role in the PMM provides an exemplar for an overarching human resource migration and recruitment role throughout the EU. The role of the WHO in influencing and overseeing the recruitment of doctors throughout the EU could be an opportunity for improved distribution, avoiding a reliance on market forces. Secondly, a centrally-coordinated and governed process following well-established criteria and guidance laid out in law has helped to ensure that doctors are allocated to regions of the greatest need. Finally, the deployment of primary care doctors to ensure that the needs of the whole population are met, including in hard-to-reach areas. However, Brazil should not fall into the trap of doing much, and evaluating little. Brazil is in an exciting position to conduct robust before-after studies regarding the improvement in access, outcomes and equity that the ESF has already been credited with. Evaluation must include the impact of the PMM on Cuba. PMID- 27653078 TI - Monitoring and evaluation of the PAHO/WHO cooperation project, the Mais Medicos (More Doctors) Program: a mid-term assessment. AB - Working relations between the Pan- American Health Organization/World Health Organization (PAHO/WHO) and Brazilian health institutions accumulated a long history of cooperation with mutual benefits, which in many cases were shared with other nations under various cooperation frameworks among countries for health development. A milestone in this relationship is the technical cooperation provided by PAHO/WHO to the More Doctors Program (Programa Mais Medicos - PMM). This cooperation has added both strategic value in reducing gaps in health equality and has capitalized on the unique nature of the Cuba-Brazil South-South cooperation experience, triangulated through PAHO/WHO. This paper discusses PAHO/WHO's role in the evaluation of its technical cooperation within PMM. A Monitoring and Evaluation (M&E) Framework has been developed in order to progressively identify the advances in coverage and quality of primary health care provided by the Unified Health System (Sistema Unico de Saude - SUS) through the PMM. Special attention was given to identify best practices in health services, to analyze results and impacts of the PMM, and to manage and share knowledge that has been produced by its implementation, through a web-based knowledge platform. Some relevant results of PMM are briefly presented and discussed. PMID- 27653079 TI - Impact of educational strategies in low-risk prenatal care: systematic review of randomized clinical trials. AB - This study aimed to analyze the impact of educational strategies developed in low risk prenatal care on obstetric outcomes from a systematic literature review. This review consulted databases PubMed, Medline, SciELO and Lilacs, analyzing randomized clinical trials with the following birth outcomes: birth weight, prematurity and breastfeeding, using the following combination of keywords: pre natal, antenatal visits, education, health education, pregnancy outcomes, birth weight, prematurity, breastfeeding and randomized clinical trial. Nine studies were included following quality evaluation. Actions prove to be more effective when extended to the postpartum period. Most of them occurred during home visits and had a positive impact on breastfeeding and birth weight. The establishment of groups of pregnant women contributed to lower prevalence of prematurity. Breastfeeding was found to be the outcome most sensitive to educational strategies. Educational practices during the prenatal period contributed to favorable obstetric outcomes as they minimized pregnant women concerns and anxiety during the pregnancy process, preparing them for childbirth and postpartum, and should be incorporated into health services' work process. PMID- 27653080 TI - Teaching-Service integration within the National Professional Health Education Reorientation Program. AB - This integrative literature review aimed at identifying the characteristics and describing how teaching-service integration is expressed in studies on Pro-Saude (Charitable institution for social and hospital assistance) published in Brazil in the period 2007-2012. For the search, the term National Professional Health Education Reorientation Program was entered in the following databases: Virtual Health Library (BVS), Google Scholar and the Bank of Theses of the Coordination for the Improvement of Higher Education Personnel (CAPES). Forty-one publications were selected with the following inclusion criteria: scientific papers; theses and dissertations; studies in English, Portuguese or Spanish. The critical review of studies was performed through a comprehensive reading of the texts. Outcomes are presented in two categories: Dialogue and partnership as tools for teaching service integration and Movements of change in teaching-service through Pro Saude. Studies have shown that changes in professional education and practice are possible and necessary, especially when supported by strategies that encourage active participation of subjects and confirm teaching-service integration as opportunity for dialogue, promoted by this inducing policy. PMID- 27653082 TI - New Media, Part One: Tool Apps for Palliative Care Providers. PMID- 27653081 TI - Children's Health in Brazil: orienting basic network to Primary Health Care. AB - This is an integrative literature review that analyzed the scientific knowledge produced on the orientation of Brazilian basic care services to primary health care focusing on child health. Searches were carried out in SciELO, Lilacs and Medline databases using descriptors "primary health care", "family health program", "child health" and "evaluation of health services". Studies published in Portuguese, English and Spanish between 2000 and 2013 were selected. A total of 32 studies were chosen and characterized in relation to the features of primary health care, region of the country, type of study and authors' practice area. A thematic review of studies was conducted and resulted in two categories: child care in the context of Brazilian primary health care and primary health care features: limitations to child care. It can be understood that Brazilian primary health care services are heterogeneous regarding the presence and scope of essential child care characteristics. There is a lack of structural and process changes in the services to substantially plan child care actions in basic care. PMID- 27653083 TI - Introduction of the American Pediatric Society's 2016 John Howland Award Recipient, Barbara J. Stoll, MD. PMID- 27653084 TI - Evaluation of four commercial virological assays for early infant HIV-1 diagnosis using dried blood specimens. AB - BACKGROUND: Early infant diagnosis (EID) of HIV-1 is necessary to reduce HIV related mortality. As maternal antibodies transferred across the placenta may persist up to 18 mo, commercial virological assays (CVAs) are needed. This study compares four CVAs for EID using dried blood specimens (DBS) from HIV-1-exposed infants. METHODS: DBS from 68 infants born to HIV-1-infected women were collected from November 2012 to December 2013 in Equatorial Guinea. Four CVAs were performed: Siemens VERSANT HIV-1 RNA 1.0 kPCR assay, Roche CAP/CTM Quantitative Test v2.0, CAP/CTM Qualitative Tests v1.0 and v2.0. Definitive diagnosis was established following World Health Organization (WHO) recommendations. RESULTS: Two HIV-1-infected infants (2.9%) were detected by the four CVAs while 49 (72%) resulted negative. Discordant results were observed in 17 (25%) infants and HIV-1 infection was excluded in 14 patients when virological and serological testing was performed in additional DBS. Different false-positive rates HIV-1 were observed with Roche assays. CONCLUSION: CVAs using DBS were useful for EID, although discrepant results were common. Further research is required to reduce false-positive results that could result in wrong diagnosis and unneeded treatment. We propose caution with low viral load (VL) values when using VL assays. Clear guidelines are required for EID of HIV-exposed infants with discrepant virological results. PMID- 27653085 TI - Assessing resting energy expenditure in overweight and obese adolescents in a clinical setting: validity of a handheld indirect calorimeter. AB - BACKGROUND: Accurately determining energy requirements is key for nutritional management of pediatric obesity. Recently, a portable handheld indirect calorimeter, MedGem (MG) has become available to measure resting energy expenditure (REE). Our work aims to determine the clinical validity and usefulness of MG to measure REE in overweight and obese adolescents. METHODS: Thirty-nine overweight and obese adolescents (16 male (M): 23 female (F), 15.2 +/ 1.9 y, BMI percentile: 98.6 +/- 2.2%) and 15 normal weight adolescents (7M: 8F, age 15.2 +/- 2.0 y, BMI percentile: 39.2 +/- 20.9%) participated. REE was measured with both MG and standard indirect calorimeter (VMax) in random order. RESULTS: MG REE (1,600 +/- 372 kcal/d) was lower than VMax REE (1,727 +/- 327 kcal/) in the overweight and obese adolescents. Bland Altman analysis (MG -VMax) showed a mean bias of -127 kcal/d (95% CI = -72 to -182 kcal/d, P < 0.001), and a proportional bias existed such that lower measured REE by VMax was underestimated by MG, and higher measured REE by VMax were overestimated by MG. CONCLUSION: MG systematically underestimates REE in the overweight and adolescent population, thus the MG portable indirect calorimeter is not recommended for routine use. Considering that it is a systematic underestimation of REE, MG may be clinically acceptable, only if used with caution. PMID- 27653086 TI - Medical morbidities and DNA methylation of NR3C1 in preterm infants. AB - BACKGROUND: Although there are no accepted "normal" levels of circulating cortisol in preterm infants, critically ill preterm infants show lower cortisol levels than healthy preterm infants. The regulation of cortisol reactivity by epigenetic changes in glucocorticoid receptor gene (NR3C1) expression has been demonstrated. This study aims to examine the relationship between medical morbidities in preterm infants and DNA methylation of NR3C1. METHODS: Pyrosequencing was used to determine DNA methylation in CpG sites 1-4 of promoter region 1F of NR3C1. Cluster analysis placed 67 preterm infants born <1,500 g into groups based on medical morbidities. The DNA methylation pattern was compared across groups. RESULTS: Cluster analysis identified a high medical risk cluster and a low medical risk cluster. A Mann-Whitney U-test showed lower methylation at CpG1 for infants in the high-risk group (M = 0.336, SE = 0.084) than infants in the low-risk group (M = 0.617, SE = 0.109, P = 0.032). The false discovery rate was low (q = 0.025). Cohen's D effect size was moderate (0.525). CONCLUSION: Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels. PMID- 27653087 TI - American Pediatric Society's 2016 John Howland Award acceptance lecture: every newborn matters-progress and promise. PMID- 27653088 TI - Association of desaturase activity and C-reactive protein in European children. AB - BACKGROUND: Desaturase enzymes influence the fatty acid (FA) composition of body tissues and their activity affects the conversion rate of saturated to monounsaturated FA and of polyunsaturated FA (PUFA) to long-chain PUFA. Desaturase activity has further been shown to be associated with inflammation. We investigate the association between delta-9 (D9D), delta-6 (D6D) and delta-5 desaturase (D5D) activity and high-sensitive C-reactive protein (CRP) in young children. METHODS: In the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort study children were examined at baseline (T0) and after 2 y (T1). D9D, D6D, and D5D activities were estimated from T0 product-precursor FA ratios. CRP was measured at T0 and T1. In a subsample of 1,943 children with available information on FA, CRP, and covariates, the cross-sectional and longitudinal associations of desaturase activity and CRP were analyzed. RESULTS: Cross-sectionally, a D9D increase of 0.01 units was associated with a 11% higher risk of having a serum CRP >= Percentile 75 (P75) (OR, 99% CI: 1.11 (1.01; 1.22)) whereas D6D and D5D were not associated with CRP. No significant associations were observed between baseline desaturase activity and CRP 2 y later. CONCLUSION: Cross-sectionally, our results indicate a positive association of D9D and CRP independent of weight status. High D9D activity may increase the risk of subclinical inflammation which is associated with metabolic disorders. As D9D expression increases with higher intake of saturated FA and carbohydrates, dietary changes may influence D9D activity and thus CRP. However, it remains to be investigated whether there is a causal relationship between D9D activity and CRP. PMID- 27653091 TI - Thousands wait for A&E beds, says RCN. AB - Thousands of patients are spending the night on trolleys in A&E departments while they wait for beds, the RCN claimed this week. PMID- 27653090 TI - Waiting for God? AB - 'Wet leaves on the line', may not be the most plausible of explanations for British Rail delays, but at least it is an excuse. The NHS doesn't even have 'wet leaves' to fall back on to justify the endless waiting that now permeates the service. PMID- 27653089 TI - Comparing nodal versus bony metastatic spread using tumour phylogenies. AB - The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extraprostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extraprostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage. PMID- 27653092 TI - Regraded nurses face huge tax bills. AB - Nurses receiving lump sum payments after winning clinical regrading appeals are being hit with massive tax bills. PMID- 27653093 TI - DoH nursing division at risk. AB - An uncertain future hangs over the Department of Health's nursing division following the announcement of the latest NHS management review. PMID- 27653094 TI - ? AB - Edinburgh opthalmic nurse Caron Jenkins has just returned front the heat of a Zimbabwean summer where she worked on a project to help restore the sight of people suffering from cataracts. As a volunteer with the youth development charity Raleigh International, Caron managed the programme for the American charity Scientific Eye Expeditions (SEE). She led a team of volunteers who helped to screen nearly 2,500 people. 'It has been a real challenge and I feel honoured to be involved in something so worthwhile,' she said. Caron also helped to build a clinic in a remote rural area. PMID- 27653095 TI - Pay review bodies resignation rumours. AB - Rumours were rife last week that the health sector's pay review bodies were set to resign en masse in protest at the government's public sector pay clampdown. PMID- 27653096 TI - Sacked staff win compensation battle. AB - A group of nurses and auxiliaries unfairly dismissed from an independent Yorkshire hospital have won their fight for compensation - four years after they were sacked. PMID- 27653097 TI - ? AB - Nurses from Glasgow's Western Infirmary feature in a Channel Four Cutting Edge programme to be broadcast next Monday. Filmed over a two-month period last summer, the documentary begins as the nurses prepare for their early shift and explores some of the feelings the staff have about the work. 'Outside of my shift I'm probably one of the least caring people out. But because you're paid to be caring, anyone could do it,' says staff nurse Ian Molloy. Another staff nurse, Liz Marshall, describes herself as 'a glorified waitress, a glorified cleaner and a glorified social worker'. 'You do all these jobs and you just wear a nurse's uniform,' she says. [Figure: see text]. PMID- 27653098 TI - ENB report on Project 2000 to lose critical foreword. AB - The ENB confirmed last week that it would publish in the spring a controversial report which highlights major problems with Project 2000. PMID- 27653099 TI - Morale slumps after job cuts threat. AB - Morale among nurses at a Cheshire trust hospital has hit rock bottom as up to 40 nursing posts are set to go, the RCN claimed last week. PMID- 27653100 TI - Councils slam policy on mental health. AB - Confusion over government policy on mental health is causing major problems, including poor access and fierce competition for scarce resources, with the prospect of an even bleaker future for service users, it was claimed this week. PMID- 27653101 TI - Hospitals 'ignore standards for patient nutrition'. AB - Many hospitals are failing to meet basic nutrition standards, while over a third of doctors believe their patients are nor routinely weighed, according to a survey of more than 1,000 medical staff. PMID- 27653102 TI - Nurse set for operating theatre roadshow. AB - A theatre nurse is preparing to I take to the road as part of a unique project that will see a travelling operating theatre taken to GP surgeries. PMID- 27653104 TI - DoH 'wasted drug misuse cash'. AB - A nurse expert has criticised a Department of Health campaign to prevent drug and solvent misuse by young people, saying the money could have been better spent on local drug prevention and treatment initiatives. PMID- 27653105 TI - Study awards. AB - Five nurses from West Yorkshire have won awards worth L10,000 to develop their studies. Jacqueline Broadbent from Leeds, Carol Hendrick from Halifax, Kathryn Robinson from Huddersfield, Lilian Saunders from Dewsbury and Elaine Weforzewski from Bradford all received Smith and Nephew Foundation awards. PMID- 27653106 TI - Allitt inquiry to report soon. AB - The Clothier Inquiry into the Beverley Allitt murders looks set to publish its findings at the end of this month. PMID- 27653107 TI - Braer study reveals ongoing ill-health. AB - Some Shetland Islanders are continuing to experience health problems which they attribute to the Braer disaster a year after the tanker went aground off the South Mainland, a nurse researcher said last week. PMID- 27653108 TI - Help your patients to quit the habit. AB - A handbook for nurses, health visitors and midwives to help patients stop smoking has been launched by QUIT, the UK charity which aims to motivate people to break the habit. PMID- 27653109 TI - A&E advice line 'can save time and money'. AB - A nurse-run advice line in accident and emergency departments can benefit patients and save both time and money, according to recent research in Cambridgeshire. PMID- 27653110 TI - Call to press MPs over tobacco ads. AB - Nurses are being asked to write to their MPs to secure their support for a private members bill that proposes a ban on tobacco advertising. PMID- 27653112 TI - World news. AB - Japan Abortion is the main method of birth control because most men will not use condoms and other contraceptive methods are not widely available, a member of the Japanese Parliament has claimed. PMID- 27653113 TI - HEA fears complacency over immunisation. AB - The Health Education Authority has called on nurses and health professionals to support its new year Immunisation Promotion Campaign aimed at eradicating vaccine preventable childhood diseases. PMID- 27653114 TI - ? AB - Not to be sneezed at: London's Science Museum staged a special exhibition showing the history and effects of Beijing flu. which was first identified in the Chinese capital in 1992. PMID- 27653115 TI - Epilepsy liaison nurse programme launched. AB - UK nurses are to play a key role in improving epilepsy care through the formation of a new epilepsy liaison nurse programme. PMID- 27653117 TI - Hope for TS sufferers as gene is discovered. AB - The UK's 6,000 tuberous sclerosis (TS) sufferers have been given hope with the discovery of a gene thought to cause the disorder. TS affects more than a million people worldwide and causes a range of conditions, including epilepsy, learning difficulties, autism and kidney problems. PMID- 27653118 TI - Preconditioning effect from angina pectoris? AB - The reduced blood flow which causes the pain of angina pectoris might have a protective effect, researchers report. PMID- 27653119 TI - Artificial surfactant in cases of near drowning. AB - Artificial surfactant might be a useful treatment for cases of near drowning, according to a report from Kettering. PMID- 27653120 TI - Metoprolol benefits in cardiomyopathy. AB - Giving metoprolol to patients with symptomatic idiopathic dilated cardiomyopathy prevents clinical deterioration, improves symptoms, cardiac function, and quality of life. PMID- 27653121 TI - Vitamin intake and vascular disease. AB - Increasing vitamin intake might reduce the risk of vascular disease in older people, American researchers suggest. PMID- 27653122 TI - Instrument coating cuts down risk of clots. AB - Coating instruments with a lipid compound might reduce the risks of blood clotting and infection. PMID- 27653123 TI - Wilson's model of family caregiving. AB - The stresses and burdens imposed upon the carers of relatives with Alzheimer's disease are well understood, but effective strategies to enable health professionals to assess the effects of these stressors appropriately hat e not been widely utilised. The authors describe one such approach and through the use of short case histories demonstrate how it can be used to represent the carer's perspective accurately. PMID- 27653124 TI - Save your arts from the elbow. AB - Over the past 35 years, I have witnessed an apparent quest to make nursing into something which it isn't, and to ignore the simple natural healing process which it is. I believe that nursing (nurturing) effectively promotes self-healing. PMID- 27653125 TI - Back from the grave - saved by Bristol. AB - Nat Health, the private investigator featured in Viewpoint's columns, does not of course, exist. I invented him more or less as a laugh about the NI IS - God knows we need it at times. PMID- 27653126 TI - There's no need to envy NVQs. AB - Your news article, NVQ plans could deskill OH nursing (December 8), quotes a Sarah Dymott as speaking vehemently about a subject that I feel she knows little about. PMID- 27653127 TI - Acute nurse on rotating split. AB - Linda Nazarko's article, Losing the battle of all NHS mothers (Viewpoint, November 24) stuck a chord with me as it echoed the plights I have experienced. PMID- 27653128 TI - Don't relax with sex-mix patients. AB - Jackie De Rochas quite rightly referred to the anxiety caused to many people allocated to mixed sex wards, 'particularly adults and senior citizens who find this objectionable and are not prepared to be cared for in such environments' (Mixed sex feeling ignored by NHS, Letters, December 8). PMID- 27653129 TI - Information exchange. AB - *We use aromatherapy at the hospital where I am a staff nurse, but have noticed that after using lavender essential oil, four patients have had convulsions. Each had some cerebral involvement - a brain tumour or cerebral metastases, and we are concerned whether lavender oil had anything to do with it. PMID- 27653130 TI - Taken further to task over NVQs. AB - Nursing will not become a 'deskilled and mechanistic profession', as Sarah Dymott claimed. PMID- 27653131 TI - Pulling up the pill pushers. AB - The meal was superb. What a spread - quality ingredients, expertly cooked, efficiently and unobtrusively served, and all in a delightful setting, with soft music, intimate tables and knee-deep carpets. PMID- 27653133 TI - The Nursing of Families Feetham S L The nursing of families et al SAGE 308pp L14.50 0-8039-4715-1. AB - The Nursing of Families uses selected papers from the Second International Conference on Family Nursing held in the USA. PMID- 27653132 TI - In Charge of the Ward, 3rd edition A Matthews J Whelan In Charge of the Ward, 3rd edition Blackwell Scientific 278pp L11.99 0-632-03448-3. AB - The only 'negative' criticism that I can make of In Charge of the Ward, 3rd edition, is that it is not pocket-sized to allow for continual use. It is an invaluable source of practical and professional information on a variety of issues, reflecting the considerable changes in nursing. The style of the book makes it easy to read, each chapter being packed full of relevant information for managing a ward. PMID- 27653134 TI - Nursing practice in the UK and North America E Levine P Leatt and K Poulton Nursing practice in the UK and north america Chapman & Hall 328pp L15.50 0-412 33490-9. AB - Nursing Practice in the UK and North America is divided into five parts and considers first the conceptual background to the book, an interesting and illuminating account of statistics and factors which have led to the development of the health care systems in the United Kingdom, the USA and Canada. PMID- 27653135 TI - Top tips by the ton Jamsa K Jama's 100I doS and PC Tips 1992 . Osborne , McGraw Hill . L31.97 . Jamsa K Jama's 1001 Windows Tips . 1993 . Jamsa Press . L36.95 . AB - Kris Jamsa undertook a courageous enterprise when he set out to find 1,001 tips for the world's most used operating system, and then another 1,001 tips for Windows. PMID- 27653136 TI - Caring for the family hit by HIV. AB - The World Health Organization has estimated that ten million adults in the developing countries of Africa, Asia and Latin America are infected with HIV. The ratio of infected males and females is almost equal, indicating the predominance of heterosexual transmission. PMID- 27653138 TI - What's on. PMID- 27653137 TI - HIV and the long-term mentally ill. AB - As Project 2000 students we were allocated to a psychiatric rehabilitation hospital tor people with long-term mental illness for a module of the common foundation programme. During our stay we were required to examine the health needs of the clients, identify those that were not being met and suggest ways of addressing them. PMID- 27653139 TI - Career listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. PMID- 27653141 TI - Radiological and Clinical Evaluation of the Transosseous Cortical Button Technique in Distal Biceps Tendon Repair. AB - PURPOSE: One of the options to repair a ruptured distal biceps tendon to the radial tuberosity is by means of a transosseous cortical button. Although excellent functional outcomes have been reported, no studies have been performed to quantify the effect of the transosseous fixation technique on the radius. Our study evaluated the clinical outcome and radiological outcome of this technique. The main goal of this study was to evaluate the radiographic evolution of the bone tunnel in the radius. METHODS: Patients with an acute distal biceps tendon rupture treated with a transosseous cortical button were invited to take part in the study. Fourteen patients were included in the final analysis. All patients were evaluated both clinically and by computed tomography scanning of the proximal radius after a minimum follow-up of 2 years. Outcomes were recorded using the visual analog scale score for pain, the Mayo Elbow Performance Score, and Disabilities of the Arm, Shoulder, and Hand scores. Bone tunnel volume was measured with semiautomated computed tomography segmentation using image processing software. RESULTS: There were no failures of fixation in the patient group examined. Elbow mobility, arm, and forearm circumference were symmetric for all patients. Average visual analog scale for pain was less than 2. Mean Disabilities of the Arm, Shoulder, and Hand score and Mayo Elbow Performance Score were 2.3 and 97.6, respectively. Computed tomography images showed an average closure of the radial bony tunnel of 64% of the initial volume. CONCLUSIONS: Biceps tendon repair with cortical button fixation only shows partial tunnel closure. This could reduce the risk of potential complications due to osteolysis, such as radius fracture or hardware failure. Functional results were excellent and comparable to other fixation methods. The role of interference screws in transosseous cortical button techniques to strengthen the repair and to avoid osteolysis may therefore be questioned. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 27653142 TI - Extensor Carpi Ulnaris Subsheath Reconstruction. AB - Acute extensor carpi ulnaris (ECU) subsheath injury and chronic subsheath insufficiency may result in symptomatic ECU instability at the level of the distal ulna osseous sulcus. Associated ulnocarpal (ie, triangular fibrocartilage complex) and ECU intrinsic tendinopathic changes may accompany subsheath pathologies and require concomitant treatment. Surgical treatment is indicated in refractory cases despite nonoperative treatment and may consist of repair of the torn edge of the ECU subsheath or, more frequently, reconstruction utilizing a radially based extensor retinacular sling. An ECU subsheath reconstructive technique is detailed. PMID- 27653140 TI - Effect of Intermittent versus Chronic Calorie Restriction on Tumor Incidence: A Systematic Review and Meta-Analysis of Animal Studies. AB - Both chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) have shown anticancer effects. However, the direct evidence comparing ICR to CCR with respect to cancer prevention is controversial and inconclusive. PubMed and Web of Science were searched on November 25, 2015. The relative risk (RR) [95% confidence interval (CI)] was calculated for tumor incidence, and the standardised mean difference (95% CI) was computed for levels of serum insulin like growth factor-1 (IGF-1), leptin, and adiponectin using a random-effects meta analysis. Sixteen studies were identified, including 11 using genetically engineered mouse models (908 animals with 38-76 weeks of follow-up) and 5 using chemically induced rat models (379 animals with 7-18 weeks of follow-up). Compared to CCR, ICR decreased tumor incidence in genetically engineered models (RR = 0.57; 95% CI: 0.37, 0.88) but increased the risk in chemically induced models (RR = 1.53, 95% CI: 1.13, 2.06). It appears that ICR decreases IGF-1 and leptin and increases adiponectin in genetically engineered models. Thus, the evidence suggests that ICR exerts greater anticancer effect in genetically engineered mouse models but weaker cancer prevention benefit in chemically induced rat models as compared to CCR. Further studies are warranted to confirm our findings and elucidate the mechanisms responsible for these effects. PMID- 27653143 TI - Dupuytren in a Child: Rare Presentation of a Rare Clinical Entity. AB - Dupuytren disease in children younger than 10 years is rare and only 8 histologically proven cases have been reported. A histologically proven Dupuytren disease in a 10-year-old with an uncommon clinical presentation as a nodule on the radial side of the middle phalanx of the little finger is documented. Dupuytren's disease should be in the differential diagnosis in cases of nodules and contractures in the palm and fingers of children. PMID- 27653145 TI - Candida tropicalis biofilm inhibition by ZnO nanoparticles and EDTA. AB - OBJECTIVE: Biofilm of Candida tropicalis denote as a complex cellular congregation with major implication in pathogenesis. This lifestyle of fungus as a biofilm can inhibit immune system and antifungal therapy in treatment of infectious disease especially medical device associated chronic disease. In this study effects of Zinc Oxide (ZnO) nanoparticles and EDTA were evaluated on C. tropicalis biofilm by using different techniques. ZnO nanoparticles were synthesized from Egg albumin. DESIGN: To assay the formation of biofilm of yeast cells like Fluconazole-susceptible C. tropicalis (ATCC 13,803) and fluconazole resistant standard strains of C. tropicalis (ATCC 750) were grown in 24 well plates and antifungal effect of ZnO and EDTA were evaluated on C. tropicalis biofilm using ATP bioluminescence and tetrasodium salt (XTT) reduction assays. RESULTS: Synthesized ZnO NPs and EDTA had effective antifungal properties at the concentration of 5.2, 8.6MUg/ml for Fluconazole susceptible strain and 5.42, 10.8MUg/ml Fluconazole resistant strains of C. tropicalis biofilms compared to fluconazole drug. CONCLUSION: In present study we conclude, ZnO considered as a new agent in field of prevention C. tropicalis biofilms especially biofilms formed surface of medical device. PMID- 27653146 TI - The role of osteocytes during experimental orthodontic tooth movement: A review. AB - OBJECTIVE: To explore the types of orthodontic force-induced mechanical stimuli that regulate osteocyte function. DESIGN: In orthodontics, a tooth can be moved through the alveolar bone when an appropriate orthodontic force is applied. These mechanical loads stimulate cells within the bone tissue around the tooth. These cellular responses lead to bone resorption on the side of the tooth where the pressure has been applied and bone deposition on the side of the tooth experiencing tension. Recently, osteocytes were identified to function as mechano sensory cells in bone tissue that direct bone resorption and bone formation. Based on recent literature, the proposed function of osteocytes during orthodontic tooth movement is explored with better understanding. RESULTS: Several stimuli regulating osteocyte function have been highlighted, and their potential roles in events initiating osteocyte sensing of orthodontic force have been explored in detail. The most popular hypotheses for osteocyte response include stress-induced bone matrix deformation/microcrack formation and fluid flow shear stress. CONCLUSIONS: Understanding osteocyte function under mechanical stress may have profound implications in future orthodontic treatments. PMID- 27653147 TI - Examination of stride-to-stride independence of selected lower extremity kinematic and temporal variables during treadmill walking. AB - The purpose of this study was to examine the nature of the intra-subject independence among strides during treadmill walking. We investigated the strength of the relationships among strides sampled in different ways from a population of observed strides. Eighteen asymptomatic subjects walked on a treadmill at 1.4+/ 0.1m/s. Maximum angles and ranges of motion from the ankle, knee and hip joints, as well as stride duration were obtained and autocorrelation coefficients (AC) for 3 lags were calculated among 12 strides sampled consecutively (CS), in order but non-adjacently (NA), and randomly (RA). Ninety-nine percent of AC values were within Bartlett's 95% confidence interval limits and thus the strides were not considered significantly autocorrelated. The results support the hypothesis that strides obtained from an individual walking on a treadmill can be statistically independent. This supports the theoretical assumption that in some circumstances humans can be modeled as random sample generators due to inherent movement variability. The ability to assess statistically clinical intervention provides objective rigor for evaluating rehabilitation outcomes. PMID- 27653144 TI - GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation. AB - Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-beta) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior-posterior patterning disorder. Here we show a role for GDF11 in bone remodelling. GDF11 treatment leads to bone loss in both young and aged mice. GDF11 inhibits osteoblast differentiation and also stimulates RANKL-induced osteoclastogenesis through Smad2/3 and c-Fos-dependent induction of Nfatc1. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Our data demonstrate that GDF11 is a previously unrecognized regulator of bone remodelling and suggest that GDF11 is a potential target for treatment of osteoporosis. PMID- 27653148 TI - Development of a smartphone application to measure reaction times during walking. AB - Dual-task methodology is useful to assess walking ability. We developed a smartphone application to measure reaction times (RTs) during walking. We can assess the attentional demands for a task from the RTs. In experiment 1, the accuracy and precision of the RT application were evaluated in two subjects. We investigated the agreement between the RTs calculated based on the external inertial sensor and the RT application; the application was installed in two smartphone models with different levels of performance. Additionally, in experiment 2, we investigated the RTs under 4 conditions: sitting, overground walking, treadmill walking, and auditory cued overground walking (n=19). The constant systematic error and low standard deviation of the difference between the two methods was demonstrated; this depended on the sampling interval of each sensor. The RTs in overground walking were increased compared with sitting and decreased compared with treadmill walking and auditory cued overground walking. Overall, the RTs were more decreased in the smartphone model with the shorter sampling interval. The RT application would be valid within a smartphone with a similar level of performance, because bias and precision are strongly dependent on the sampling interval. In field tests under different walking conditions, the RT application obtained results similar to those seen in previous studies and could identify even slight differences if there were many trials. The developed RT application will be a simple tool that is able to assess attentional demands during dual-task walking. PMID- 27653149 TI - Long-term changes in femoral anteversion and hip rotation following femoral derotational osteotomy in children with cerebral palsy. AB - BACKGROUND: Excessive femoral anteversion is common in cerebral palsy (CP), is often associated with internal hip rotation during gait, and is frequently treated with a femoral derotational osteotomy (FDO). Concerns exist regarding long-term maintenance of surgical outcomes. Past studies report varying rates of recurrence, but none have employed a control group. METHODS: We conducted a retrospective analysis examining long-term (~5 years) changes in anteversion and hip rotation following FDO in children with CP. We included a control group that was matched for age and exhibited excessive anteversion (>30 degrees ) but did not undergo an FDO. Anteversion, mean stance hip rotation, and rates of problematic remodeling and recurrence were assessed (>15 degrees change and final level outside of normal limits). RESULTS: The control group was reasonably well matched, but exhibited 9 degrees less anteversion and 3 degrees less internal hip rotation at the pre time point. At a five year follow-up, the FDO group had less anteversion than the control group (20 degrees vs. 35 degrees , p<0.05). The mean stance phase hip rotation did not differ between the groups (4 degrees vs. 5 degrees , p=0.17). Over one third of limbs remained excessively internal in both groups (FDO: 34%, Control: 37%). Rates of problematic recurrence and remodeling were low (0%-11%). CONCLUSIONS: An FDO is an effective way to correct anteversion in children with CP. Long-term hip rotation is not fully corrected by the procedure, and is not superior to a reasonably well matched control group. Rates of problematic recurrence and remodeling are low, and do not differ between the groups. PMID- 27653150 TI - A validation of neural co-activation as a measure of attentional focus in a postural task. AB - Postural threat can induce conscious involvement in movement control. This internal focus has been implicated in compromising attentional processing efficiency during postural control, leading to behavioral adaptations that might increase the risk of falling in the elderly. It is suggested that electroencephalography (EEG) coherence, or 'communication', between T3 (verbal analytical) and Fz (motor-planning) regions may provide an objective measure of internal focus in learned movement skills. However, it is currently unknown whether this experimental technique can be applied to the control of gait and posture; skills which develop early in life, without the use of declarative knowledge/explicit verbal cues to guide performance. We validate the utility of the EEG T3-Fz coherence analysis in a postural task. A total of 24 young adults produced small voluntary swaying movements in medial-lateral or anterior posterior direction under conditions that directed their attentional focus either internally or externally. Although EEG coherence was sensitive to voluntary changes in attentional focus, the lack of observed between-group (High/Low-trait reinvestment) difference in coherence may suggest that younger adults cannot be assumed to utilize explicit verbal cues to control voluntary postural sway unless explicitly instructed to do so. As a result, while these results indicate that EEG T3-Fz is a valid technique for assessing attentional focus in postural tasks, our data do not support the clinical application of this method of analysis in providing an objective indication of trait-reinvestment in tasks involving voluntary postural sway. PMID- 27653151 TI - Control of false positives in randomized phase III clinical trials. AB - Randomized Phase III clinical trials serve as the gold-standard for the evaluation of the efficacy of a medical intervention. Although research and development in earlier stages together with rigorous statistical examination assure a small probability of false positive for a given trial, it is unclear how many false positives were generated from the large number of randomized Phase III trials from the biopharmaceutical industry in the United States. The proportion of comparisons in Phase III trials where the medical intervention has null or negative efficacy, or proportion of null or negative (PNN), is at the central position for the estimation and control of the number of false positives. We seek to estimate PNN using a new Bayesian deconvolution method. Using data from clinicaltrials.gov and other data sources, we identified 1393 trials completed in 2008-2012 that meet our study entry criteria, which are dominated by trials on drugs for treatment purpose. Among the 1221 trials with results available on the selected comparisons, 789 (64.6%) show statistically significant superiority of the intervention, with 561 (45.9%) having a two-sided p-value less than 0.001. The PNN is estimated to be no more than 7-9%. Based on the PNN, we estimated that 18-22% of the trials have at least one comparison with null or negative efficacy, leading to an expectation of no more than 6-8 trials with at least one false positive comparison over a 5-year period. PMID- 27653152 TI - Electron Microscopy Findings in N-Methyl-N-Nitrosourea-Induced Mammary Tumors. AB - Although the rat model of mammary tumors chemically induced by N-methyl-N nitrosourea (MNU) has been frequently used by several research teams, there is a lack of ultrastructural studies in this field. The main aim of this work was to perform an ultrastructural characterization of MNU-induced mammary tumors in female rats. Some alterations previously reported in human mammary tumors, such as nucleus size and shape, accumulation of heterochromatin in the perinuclear region, and interdigitating cytoplasmic processes between cancer cells were also observed in MNU-induced mammary tumors. Although a low number of samples were analyzed by transmission electron microscopy in the present study, we consider that it may contribute to a better understanding of MNU-induced mammary carcinogenesis in a rat model. The ultrastructural characteristics of the two most frequently diagnosed mammary carcinomas described in the present work can be useful to differentiate them from other histological patterns. In addition, the loss of cytoplasm in neoplastic cells and formation of vacuoles were described. PMID- 27653153 TI - Influence of 12-week Nordic Walking training on biomarkers of endothelial function in healthy postmenopausal women. AB - BACKGROUND: The aim of this study was to evaluate the effects of a 12-week Nordic Walking (NW) intervention on nitric oxide synthase activity (eNOS), levels of antibodies against oxidatively modified low-density lipoproteins (oLAb), plasma antioxidant capacity (TAC), thiobarbituric acid reactive substance (TBARS) concentration, carbohydrate and lipid metabolism, and atherosclerosis risk factors (AIP) in postmenopausal women. METHODS: A sample of 39 women, divided into two comparable groups: training (N.=20) and control (N.=19), took part in the study. Participants in the training group performed a 12-week supervised NW training: 60-minute sessions of exercise, repeated three times per week. The biochemical and anthropometric data were obtained before and after the intervention. During the first and the last training sessions, the individual walking distance in trained group was measured. RESULTS: After the intervention, significant differences in covered distance, body mass, BMI, fat mass, insulin level (P<0.01), systolic blood pressure and TBARS concentration (P<0.05) were found in trained women. CONCLUSIONS: Applied training was able to improve functional capacity and body composition in healthy postmenopausal women. It appears to be no direct link between a significant decrease in the level of systolic blood pressure, the level of eNOS activity, TAC, oLAb and plasma TBARS concentration in trained women. It seems probable that NW training would be more effective for postmenopausal women with more severely impaired endothelial function. PMID- 27653154 TI - Validation of the iPhone app using the force platform to estimate vertical jump height. AB - BACKGROUND: Vertical jump performance has been evaluated with several devices: force platforms, contact mats, Vertec, accelerometers, infrared cameras and high velocity cameras; however, the force platform is considered the gold standard for measuring vertical jump height. The purpose of this study was to validate an iPhone app called My Jump, that measures vertical jump height by comparing it with other methods that use the force platform to estimate vertical jump height, namely, vertical velocity at take-off and time in the air. METHODS: A total of 40 sport sciences students (age 21.4+/-1.9 years) completed five countermovement jumps (CMJs) over a force platform. Thus, 200 CMJ heights were evaluated from the vertical velocity at take-off and the time in the air using the force platform, and from the time in the air with the My Jump mobile application. The height obtained was compared using the intraclass correlation coefficient (ICC). RESULTS: Correlation between APP and force platform using the time in the air was perfect (ICC=1.000, P<0.001). Correlation between APP and force platform using the vertical velocity at take-off was also very high (ICC=0.996, P<0.001), with an error margin of 0.78%. CONCLUSIONS: Therefore, these results showed that application, My Jump, is an appropriate method to evaluate the vertical jump performance; however, vertical jump height is slightly overestimated compared with that of the force platform. PMID- 27653155 TI - The acute effects of interval exercise on oxidative stress and antioxidant status in volleyball players. AB - BACKGROUND: Volleyball is briefly described as an "interval" sport with both aerobic and anaerobic components. Exercise may influence antioxidant/prooxidant balance, which leads to differences in oxidative stress status between athletes in different sport disciplines, but the results of the previous studies are inconsistent. In this study, we aimed to determine the acute effects of exercise on oxidative stress parameters such as serum total oxidant status (TOS) and total antioxidant status (TAS) levels in volleyball players. METHODS: Thirteen male volleyball players from the same team participated in this study. The volleyball game lasted approximately 95 minutes including warm-up and cool-down periods. Blood samples were taken before the warm-up and after the cool down. Serum TOS and TAS levels were measured. Oxidative stress index (OSI), a predictor of antioxidant/prooxidant balance (TOS/TAS), was also calculated. RESULTS: The following data were revealed as median: TOS 6.84 MUmol H2O2 Eq/L (95% CI: 5.80 8.13) and 5.15 (95% CI: 4.20-6.02); TAS 1.96 mmol Trolox Eq/L (95% CI: 1.91-2.08) and 1.95 (95% CI: 1.86-2.00); and OSI indexes, 3.31 (arbitrary unit) (95% CI: 2.84-4.00) and 2.64 (95% CI: 2.26-3.18) before and after the match with respectively. Serum TOS and OSI levels were significantly lower after volleyball match when compared to before (P<0.05). There was no significant difference in serum TAS levels (P>0.05). CONCLUSIONS: In individuals who exercise active sports, TOS level has been found to be decreased while TAS level has not been affected significantly after volleyball match. Our results suggested that volleyball training may not cause oxidative stress in these players. Regular physical exercise especially, volleyball training may provide adequate protection against exercise-induced oxidative stress. PMID- 27653156 TI - The validity of forceplate data as a measure of rapid and targeted volitional movements of the centre of mass in transtibial prosthesis users. AB - PURPOSE: To validate outcome variables from the limits of stability protocol that are derived from the center of pressure with those same variables derived from the center of mass during rapid, volitional responses in transtibial prosthesis users. METHOD: Prosthesis users (n = 21) and matched controls (n = 21) executed movements while force and motion data were collected. Correlation coefficients were used to investigate relationships between center of pressure and center of mass for: x/y coordinates positions, limits of stability outcome variables and muscular reaction times. RESULTS: Significant differences were seen in correlation between x/y coordinate positions toward the intact limb (mean effect size of differences: r = .38). Limits of stability variables were positively correlated (reaction time and maximum excursion range rs: .585-.846; directional control and mean velocity range rs: .307-.472). Muscular reaction times correlated weakly with those from center of pressure (mean rs prosthesis users: .186 and controls: .101). CONCLUSIONS: Forceplate measures are valid in describing rapid, volitional movements in unilateral transtibial prosthesis users. Limits of stability outcomes extracted from center of pressure and center of mass are highly correlated, but can be sensitive to direction. Muscular reaction time correlates very little with reaction times extracted from the other variables. Implications for rehabilitation Rehabilitation programs utilizing limits of stability are valid measures of postural control in transtibial prosthesis users. Clinicians interpreting the outcomes from limits of stability need to be aware of their varying validity. Muscular reaction times correlate weakly with other measures of reaction time, highlighting the complexity of rapidly coordinating volitional movements in prosthesis users. PMID- 27653157 TI - A novel method to determine valnemulin in feedingstuffs for several animal species by liquid chromatography-electrospray tandem mass spectrometry. AB - A new method specific for the determination and unambiguous confirmation of the antibiotic valnemulin in feed for all animal species is described. Simple clean up based on solvent extraction and liquid partition is carried out prior to determination by liquid chromatography coupled to electrospray tandem mass spectrometry on a hybrid QTRAP 4000 system, in multiple reaction monitoring mode. Valnemulin is licensed in the European Union as a veterinary drug for use in feed for pigs and rabbits, but unavoidable carryover in feed for non-target species should be monitored. The method is rapid and reliable, and was validated in-house at 10, 100 and 750 ng g-1, evaluating the analytical performances according to Commission Regulation (EC) No. 882/2004. Good mean recoveries from 79.7% to 92.6%, and within-laboratory reproducibility RSDs, ranging from 6.2% to 12.1%, were measured; the limit of quantification at 10.0 ng g-1 also allows for sensitive evaluation of undesirable carryover in feed for non-target species. The results of monitoring 24 compound feeds for several animal species are also reported. PMID- 27653158 TI - Manipulating the Interfacial Energetics of n-type Silicon Photoanode for Efficient Water Oxidation. AB - The photoanodes with heterojunction behavior could enable the development of solar energy conversion, but their performance largely suffers from the poor charge separation and transport process through the multiple interfacial energy levels involved. The question is how to efficiently manipulate these energy levels. Taking the n-Si Schottky photoanode as a prototype, the undesired donor like interfacial defects and its adverse effects on charge transfer in n-Si/ITO photoanode are well recognized and diminished through the treatment on electronic energy level. The obtained n-Si/TiOx/ITO Schottky junction exhibits a highly efficient charge transport and a barrier height of 0.95 eV, which is close to the theoretical optimum for n-Si/ITO Schottky contact. Then, the holes extraction can be further facilitated through the variation of surface energy level, with the NiOOH coated ITO layer. This is confirmed by a 115% increase in surface photovoltage of the photoanodes. Eventually, an unprecedentedly low onset potential of 0.9 V (vs RHE) is realized for water oxidation among n-Si photoanodes. For the water oxidation reaction, the n-Si/TiOx/ITO/NiOOH photoanode presents a charge separation efficiency up to 100% and an injection efficiency greater than 90% at a wide voltage range. This work identifies the important role of interfacial energetics played in photoelectrochemical conversion. PMID- 27653160 TI - Rutile TiO2(011)-2 * 1 Reconstructed Surfaces with Optical Absorption over the Visible Light Spectrum. AB - The stable structures of the reconstructed rutile TiO2(011) surface are explored based on an evolutionary method. In addition to the well-known "brookite(001) like" 2 * 1 reconstruction model, three 2 * 1 reconstruction structures are revealed for the first time, all being more stable in the high Ti-rich condition. Importantly, the predicted Ti4O4-2 * 1 surface model not only is in excellent agreement with the reconstructed metastable surface detected by Tao et al. [Nat. Chem. 3, 296 (2011)] from their STM experiment but also gives a consistent formation mechanism and electronic structures with the measured surface. The computed imaginary part of the dielectric function suggests that the newly predicted reconstructed surfaces are capable of optical absorption over the entire visible light spectrum, thereby offering high potential for photocatalytic applications. PMID- 27653161 TI - Relaxation Processes of Potassium Tantalate Doped by Lithium. AB - The results of an investigation of dielectric properties of perovskite-type single crystals with solid solutions of potassium-lithium tantalate K1-xLixTaO3 are presented. Particular attention is focused on two selected concentrations of x, 2% and 4.3%, which are representative for the samples with lower and higher concentration of lithium ions, respectively. While a peak in dielectric losses, as observed at higher temperature, has just been revealed for low Li content, it becomes well developed for high lithium concentration. In such crystals there exist noticeable oxygen vacancies, and additional defects associated with lithium ions have a great influence on the dielectric losses in low temperature scope. The consideration pertains to the temperature dependence of the activation energy of the possible polaronic state in the context of lithium ion content. PMID- 27653159 TI - Sex and gender disparity in pathology, disability, referral pattern, and wait time for surgery in workers with shoulder injury. AB - BACKGROUND: The role of sex as an important biological determinant of vulnerability to sustaining injury and gender as a social determinate of access to resources, referral for medical care and perceived disability remains conflicted in injured workers. The purpose of this study was to examine sex and gender disparity following a compensable work-related shoulder injury. METHODS: This study involved cross-sectional analyses of data of two independent samples of workers with shoulder injury. Measures of disability and pain were the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and Numerical Pain Rating Scale (NPRS) for patients seen at an Early Shoulder Physician Assessment (ESPA) program and the American Shoulder and Elbow Surgeons (ASES) assessment form and Visual Analogue Scale (VAS) for the sample who underwent surgery. RESULTS: The files of 1000 (443 females, 557 men) consecutive patients seen at an ESPA program and 150 (44 females, and 106 men) consecutive patients who underwent rotator cuff surgery (repair or decompression) were reviewed. Significant gender disparity was observed in the referral pattern of injured workers seen at the ESPA program who were referred for surgical consultation (22 vs. 78 % for females and males respectively, p < 0.0001). The independent rotator cuff surgical group had a similar gender discrepancy (29 % vs. 71 %, p < 0.0001). The timeframe from injury to surgery was longer in women in the surgical group (p = 0.01). As well, women waited longer from the date of consent to date of surgery (p = 0.04). Women had higher incidence of repetitive injuries (p = 0.01) with men reporting higher incidence of falls (p = 0.01). Women seen at the ESPA program were more disabled than men (p = 0.02). Women in both samples had a higher rate of medication consumption than men (p = 0.01 to <0.0001). Men seen at the ESPA program had a higher prevalence of full thickness rotator cuff tears (p < 0.0001) and labral pathology (p = 0.01). However, these pathologies did not explain gender disparity in the subsample of ESPA who were referred for surgical consultation or those who had surgery. CONCLUSIONS: Sex and gender disparity exists in workers with shoulder injuries and is evident in the mechanism of injury, perceived disability, medication consumption, referral pattern, and wait time for surgery. PMID- 27653162 TI - Update on innate immunity and perspectives on metabolite regulation in acute pancreatitis. AB - PURPOSE OF REVIEW: Acute pancreatitis is a major cause of gastrointestinal morbidity for which specific therapy is greatly needed to prevent progression to and induce resolution of severe disease. RECENT FINDINGS: Innate immune components and metabolite signaling are recently identified as strong determinants of disease severity and resolution in acute pancreatitis and this work will be discussed herein. SUMMARY: Targeting innate immune cell populations and metabolite signaling pathways in acute pancreatitis may result in broader and ultimately more efficacious re-direction of the inflammatory programme toward disease resolution and improved clinical outcomes. PMID- 27653163 TI - Gastrointestinal defense mechanisms. AB - PURPOSE OF REVIEW: To summarize and illuminate the recent findings regarding gastroduodenal mucosal defense mechanisms and the specific biomolecules involved in regulating this process, such as glucagon-like peptides (GLPs). RECENT FINDINGS: There has been a growing interest in luminal nutrient chemosensing and its physiological effects throughout the digestive system. From the ingestion of food in the oral cavity to the processing and absorption of nutrients in the intestines, nutrient chemosensing receptors signal the production and release of numerous bioactive peptides from enteroendocrine cells, such as the proglucagon derived peptides. There has been a major emphasis on two proglucagon-derived peptides, namely GLP-1 and GLP-2, due to their apparent beneficial effect on gut structure, function, and on metabolic processes. As an incretin, GLP-1 not only enhances the effect and release of insulin on pancreatic betacells but also has been implicated in having trophic effects on the intestinal epithelium. In addition, GLP-2, the other major proglucagon-derived peptide, has potent intestinotrophic effects, such as increasing the rate of mucosal stem cell proliferation, mucosal blood flow, and fluid absorption, as well as augmenting the rate of duodenal bicarbonate secretion to improve gastric mucosal health and longevity. SUMMARY: Understanding the mechanisms underlying nutrient chemosensing and how it relates to GLP release can further elucidate how the gut functions in response to cellular changes and disturbances. Furthermore, a more in-depth comprehension of GLP release and its tissue-specific effects will help improve the utility of GLP-1 and GLP-2 receptor agonists in clinical settings. This, in turn, should help patients suffering from intestinal failure, malabsorption, and mucosal injury. PMID- 27653164 TI - Fixed-dose combination of zofenopril plus hydrochlorothiazide vs. irbesartan plus hydrochlorothiazide in hypertensive patients with established metabolic syndrome uncontrolled by previous monotherapy. The ZAMES study (Zofenopril in Advanced MEtabolic Syndrome). AB - OBJECTIVE: Whether all antihypertensive drugs are equally effective in patients with metabolic syndrome is still unclear. The goal of the Zofenopril in Advanced MEtabolic Syndrome (ZAMES) study was to investigate whether treatment with the fixed-dose combination of sulphydril-containing angiotensin-converting enzyme inhibitor zofenopril plus hydrochlorothiazide is at least as effective as that with the angiotensin receptor blocker irbesartan plus hydrochlorothiazide in patients with metabolic syndrome and essential hypertension, uncontrolled by a previous monotherapy. METHODS: We enrolled 721 patients in a multicenter, international (Italy and Romania), randomized, double-blind, parallel group, phase III study. Following a 1-week screening withdrawal period, 482 patients (mean age 59 +/- 10 years, 53% men) bearing a SBP at least 140 mmHg and/or DBP at least 90 mmHg plus metabolic syndrome (ATP-III criteria) were randomly allocated to a fixed-dose combination of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or irbesartan 150 mg plus hydrochlorothiazide 12.5 mg once daily for a cumulative period of 24 weeks. After 8 and 16 weeks, zofenopril and irbesartan doses were doubled in nonnormalized study participants. The study endpoint was the office DBP reduction at study end. In 20% of patients, an ambulatory blood pressure monitoring was performed. RESULTS: The prevalence of diabetes at baseline was significantly (P < 0.05) greater in the zofenopril plus hydrochlorothiazide group (82%) than in the irbesartan plus hydrochlorothiazide (73%) group. Baseline adjusted DBP reductions were superimposable (P = 0.370) with zofenopril plus hydrochlorothiazide [n = 231; 9.8 (95% confidence interval: 11.1, 8.4) mmHg] and irbesartan plus hydrochlorothiazide [n = 235; 10.4 (11.8, 9.0) mmHg]. The same was for SBP [17.0 (19.2, 14.8) mmHg zofenopril plus hydrochlorothiazide vs. 18.8 (21.0, 16.6) mmHg irbesartan plus hydrochlorothiazide, P = 0.113]. Rate of normalized and responder patients (SBP/DBP < 140/90 mmHg or SBP reduction more than 20 mmHg or DBP reduction more than 10 mmHg) did not differ at study end (65.8% and 77.5% zofenopril plus hydrochlorothiazide vs. 67.7% and 81.5% irbesartan plus hydrochlorothiazide; P = 0.695, P = 0.301). These results were confirmed in the 69 study participants undergoing ambulatory blood pressure monitoring (35 zofenopril plus hydrochlorothiazide; 34 irbesartan plus hydrochlorothiazide), with a comparable 24-h average BP reduction [BP difference between-treatment: SBP: 0.1 (-5.7, 5.9) mmHg, P = 0.975; DBP: -0.9 (-3.8, 2.0) mmHg, P = 0.541]. Both drugs attained similar BP reductions also in the last 6 h of the dosing interval [between-treatment difference SBP: 0.1 (-7.4, 7.5) mmHg P = 0.990; DBP: -0.9 (-4.4, 2.6) mmHg, P = 0.602]. Metabolic and renal indexes were not altered. Few patients were withdrawn for moderate adverse events (5% zofenopril plus hydrochlorothiazide; 5% irbesartan plus hydrochlorothiazide). CONCLUSION: This is the first study supporting the comparable antihypertensive and metabolic response to fixed-dose combinations of sulphydril-containing angiotensin-converting enzyme inhibitors (zofenopril) or angiotensin receptor blockers (Irbesartan) with a diuretic in patients with advanced metabolic syndrome and nonresponders to monotherapy. The results of this study can further improve the clinical management of high cardiovascular risk patients with hypertension and metabolic syndrome, because these two drug combinations increase the number of available combinations, which may significantly improve patients' adherence in this special clinical condition that is frequently found in everyday practice. PMID- 27653165 TI - Safety of Preoperative Use of Ticagrelor With or Without Aspirin Compared With Aspirin Alone in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Grafting. AB - Importance: The optimal timing of discontinuation of ticagrelor before cardiac surgery is controversial. Objective: To evaluate the safety of preoperative use of ticagrelor with or without aspirin in patients with acute coronary syndromes (ACS) undergoing isolated coronary artery bypass grafting (CABG) compared with aspirin alone. Design, Setting, and Participants: This prospective, multicenter clinical trial was performed at 15 European centers of cardiac surgery. Participants were patients with ACS undergoing isolated CABG from the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry between January and September 2015. Exposures: Before surgery, patients received ticagrelor with or without aspirin or aspirin alone. Main Outcomes and Measures: Severe bleeding as defined by the Universal Definition of Perioperative Bleeding (UDPB) and E-CABG bleeding classification criteria. A propensity score-matched analysis was performed to adjust for differences in baseline and operative covariates. Results: Of 2482 patients from the E-CABG registry, the study cohort included 786 (31.7%) consecutive patients with ACS (mean [SD] age, 67.1 [9.3] years; range, 32-88 years), and 132 (16.8%) were female. One-to-one propensity score matching provided 215 pairs, whose baseline and operative covariates had a standardized difference of less than 10%. Preoperative use of ticagrelor was associated with a similar risk of bleeding according to the UDPB and E-CABG bleeding classifications, but the incidence of platelet transfusion was higher in the ticagrelor group (13.5% [29 of 215] vs 6.0% [13 of 215]). Compared with those receiving aspirin alone, continuing ticagrelor up to the time of surgery or discontinuing its use less than 2 days before surgery was associated with a higher risk of platelet transfusion (22.7% [5 of 22] vs 6.4% [12 of 187]) and E CABG bleeding grades 2 and 3 (18.2% [4 of 22] vs 5.9% [11 of 187]) and tended to have an increased risk of UDPB grades 3 and 4 (22.7% [5 of 22] vs 9.6% [18 of 187]). Among patients in whom antiplatelet drug use was discontinued at least 2 days before surgery, the incidence of platelet transfusion was 12.4% (24 of 193) in the ticagrelor group and 3.6% (1 of 28) in the aspirin-alone group. Conclusions and Relevance: In propensity score-matched analyses among patients with ACS undergoing CABG, the use of preoperative ticagrelor with or without aspirin compared with aspirin alone was associated with more platelet transfusion but similar degree of bleeding; in patients receiving ticagrelor 1 day before or up until surgery, there was an increased rate of severe bleeding. PMID- 27653166 TI - The CMS Comprehensive Care Model and Racial Disparity in Joint Replacement. PMID- 27653167 TI - Improved Recovery After Laparoscopic Bilateral Inguinal Hernia Repair: Perception vs Function Improvement? PMID- 27653168 TI - A decade of hospital-based violence intervention: Benefits and shortcomings. AB - INTRODUCTION: Initial analyses of hospital-based violence intervention programs (VIPs) have demonstrated decreased violent injury recidivism. Long-term VIP performance has not been assessed. Violence intervention program quality improvement requires evaluation to identify shortcomings and client subpopulations warranting additional resources. We evaluated our case manager based VIPs to identify modifiable risk factors that most impact violent injury recidivism and determine subpopulations that need modification of targeted services. METHODS: Data on demographic variables, socioeconomic factors, needs, and injury recidivism from 2005 to 2014 were collected through our VIP database. Possible client needs included housing, education, employment, court advocacy, driver's license obtainment, and "other." Case managers assessed needs as "not needed," "identified (unmet)," and "met." chi And nonparametric tests were used to identify factors associated with recidivism reduction. RESULTS: Over the 10 year period, 466 clients were enrolled in VIP. During the program period, the violent reinjury rate was 4%, as compared with a historical control of 8% from 2000 to 2004. Women had lower rates of reinjury than men (3% vs 13%, respectively, p = 0.023). Blacks had the lowest recidivism (2%, p < 0.0001), whereas a higher rate (11%) was observed among Latinos. Although a minority of clients (5%), 100% of white clients were reinjured. Mental health services (51%), victim-of-crime compensation (48%), employment (36%), and housing (30%) were the most frequently identified needs. Expressing the need for education was significantly associated with likelihood of reinjury, an effect that was completely reversed when the need was met. CONCLUSION: This evaluation of a VIP demonstrates sustained recidivism reduction and success in addressing client needs from a traditionally underserved population. Efforts to identify and address root causes of Latino and white client reinjury should be increased. Violence intervention program prioritization of housing needs may reduce future reinjury. This study demonstrating sustainable success underscores the importance of increased integration of VIP into trauma centers nationally. LEVEL OF EVIDENCE: Therapeutic study, level III. PMID- 27653169 TI - Preperitoneal balloon tamponade for lethal closed retroperitoneal pelvic hemorrhage in a swine model: A comparable and minimally invasive alternative to open pre-peritoneal pelvic packing. AB - BACKGROUND: The management of massive pelvic fracture-associated hemorrhage is extremely challenging, particularly in the unstable patient. We sought to characterize and compare the efficacy of a minimally invasive preperitoneal balloon technique (MIB) to standard open packing. METHODS: Twenty-six swine were randomized to control (C), open preperitoneal packing technique (OP), and MIB groups. A closed extraperitoneal iliac vascular injury followed by intervention + resuscitation over a 120-minute OP and MIB efficacy was assessed by procedure time, hemodynamics, extraperitoneal tamponade pressures (ETPs), blood loss, and survival. Angiography was performed in select animals, and ETPs were also measured in humans undergoing MIB placement for an elective procedure. RESULTS: Baseline parameters (mean arterial pressure [MAP] 29, 38, and 38 mm Hg; cardiac index [CI] 3.5, 3.8, and 4.2; and EPTs 5, 4, and 5 mm Hg) were similar among C, OP, and MIB groups, respectively (all p's > 0.05). The OP and MIB groups had markedly improved MAP and CI versus C. MIB generated significantly higher ETP (28 vs 17 mm Hg), was faster to deploy (164 vs 497 seconds), and had lower total blood loss versus OP (0.7 vs 1.2 L, all p's < 0.05). OP and MIB had equivalent survival times that were significantly improved versus C (91 and 116 vs 43 minutes, p < 0.05). Survival to 2 hours was 80% with OP versus 100% in the MIB group. Angiography showed no active extravasation in both study groups, but controlled partial deflation of the MIB allowed easy visualization of extravasation. Minimally invasive preperitoneal balloon inflation in five human subjects demonstrated a significant increase in mean ETP from 2.4 to 31 mm Hg (p < 0.01). CONCLUSION: Minimally invasive preperitoneal balloon tamponade was as effective as OP in improving hemodynamics and prolonging survival times, and performed superiorly to OP in time to placement, blood loss, and generation of tamponade pressures. The MIB allows for controlled deflation and reinflation to facilitate angiographic interventions, and may represent a promising new bedside intervention in this patient population. PMID- 27653170 TI - AlCl3-Catalyzed Annulations of Ynamides Involving a Torquoselective Process for the Simultaneous Control of Central and Axial Chirality. AB - A highly torquoselective process for simultaneous control of central and axial chirality by the annulation of terminally substituted ynamides with o-quinone methides is reported. In the presence of AlCl3, a sequence comprising a [2 + 2] cycloaddition followed by the torquoselective 4pi-electrocyclic ring opening and 6pi-electrocyclic ring closure leads to highly stereoselective formation of diastereoisomeric 4-amino-2H-chromenes. Terminally unsubstituted ynamides undergo AlCl3-catalyzed [4 + 2] cycloaddition with o-quinone methides providing 2-amino 4H-chromenes. PMID- 27653171 TI - Ensifer alkalisoli sp. nov. isolated from root nodules of Sesbania cannabina grown in saline-alkaline soils. AB - A group of Sesbania cannabina rhizobia belonging to four recA genotypes of a novel group was further characterized in comparison with the related Ensifer species. They showed 98.2 to 99.9 % similarities among themselves and 92.9 to 93.3 % similarities with the most related strain Ensifer sojae CCBAU 05684T in multilocus sequence analysis of recA, atpD and glnII. The genome average nucleotide identity values between representative strain YIC4027T and the type strains of its closely related species were 81.6 to 88.9 %. Identical symbiotic gene (nodA, nodC and nifH) sequences highly similar with those in other Sesbania nodulating strains (Rhizobium sp. SIN-1, Neorhizobium huautlense S02T, Ensifer saheli ORS609T and Rhizobium sp. IRBG74) were detected. The representative strain YIC4027T could form effective nodules on its original host Sesbaniacannabina, but not on Sophora flavescens, Trifolium repens, Glycine max, Glycyrrhiza uralensis, Phaseolus vulgaris or Medicago sativa. The use of lactulose as sole carbon source, possession of C13 : 0 2-OH, C13 : 1 at 12-13, C15 : 1 iso omega9c, C17 : 0 anteiso and C18 : 0 iso and absence of C14 : 0 anteiso, C15 : 0 anteiso and C18 : 0 3-OH in fatty acids distinguished the strain YIC4027T from the type strains of its closely related species. Based on all the analyses mentioned above, we propose a novel species Ensifer alkalisoli sp. nov. and designate YIC4027T (=HAMBI 3655T=LMG 29286T) as the type strain. The genome size of YIC4027T is 5.97 Mbp, comprising 5588 predicted genes, and the DNA G+C content is 62.2 mol%. PMID- 27653172 TI - From imitation to implementation: How two- and three-year-old children learn to enforce social norms. AB - Young children enforce social norms from early on, but little research has examined how this enforcement behaviour emerges. This study investigated whether observing an adult's norm enforcement influences children's own enforcement of that norm compared with observing an action demonstration without enforcement. Additionally, children experienced enforcement either following their own (second party) or a third-party's transgression (N = 120). Results revealed that observing enforcement increased two- and three-year-old children's protest against the sanctioned action regardless of second- or third-party context. However, only three-year-olds generalized their enforcement to a novel action not matching the norm, whereas two-year-olds only protested against the previously sanctioned action. Importantly, without any enforcement demonstration, two-year olds rarely protested at all while three-year-olds did so quite frequently. Thus, providing an opportunity to imitate enforcement seems to give rise to enforcement behaviour in two-year-olds while three-year-olds already understand normative implications following a variety of cues and even apply norm enforcement without any demonstration of how to do it. Statement of contribution What is already known on this subject? Children conform to social norms from early in development. Young children from 2 to 3 years of age also enforce social norms on third parties. What does this study add? Observing enforcement by an adult increases two- and three-year-olds' protest against the sanctioned action. It does not matter whether children experienced enforcement on their own or a third party's action. Three-, but not two-year-olds, generalize their enforcement to novel actions that do not match the norm. PMID- 27653173 TI - Percutaneous coronary intervention and heart surgery learning needs of patients in Jordan. AB - AIM: This study aimed to identify and prioritize the perceived learning needs of patients who underwent percutaneous coronary intervention or open-heart surgery. BACKGROUND: Identifying learning needs for post-cardiac intervention patients is essential to establish successful health education programmes based on patient central care. METHODS: A descriptive comparative design was employed on a convenience sample of 260 patients who underwent a percutaneous coronary intervention and 105 patients who underwent open-heart surgery patients. Participants had completed the Patient Learning Needs Scale. Data were collected between 1 October 2014 and 31 June 2015. RESULTS: Patients from the two groups highly requesting health and recovery related information. They scored all learning need topics as important or highly important for them. The top priority learning need for both patient groups was 'information about wound care', and the lowest priority learning need topic was 'physical activity'. CONCLUSIONS: The learning needs of both groups were very close, which indicated that educational secondary prevention programmes' content can be prepared in a unified structure for those patients. Although, specific headings can be used to address the unique needs that emerge from having a specific cardiac interventional procedure. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The fact that wound care and medications are areas of highest learning needs for patients requires health policy decision makers to address these topics at the time of hospital discharge. In addition, a policy focus on considering patients' actual learning needs requires establishment and managerial support. As patients' learning needs might change later after discharge, the health services should be proactive and focus on continuous support for patients after hospital discharge. Secondary prevention programmes should incorporate health education topics based on patients' own views. This can be done by giving higher priority to understand patients' needs, put much more effort into how to meet patients' information needs and to create a more engaging learning environment for patients and their families. PMID- 27653174 TI - Protective effects of melatonin on bovine sperm characteristics and subsequent in vitro embryo development. AB - We aimed to investigate the effect of melatonin on bovine frozen-thawed semen and its impact on fertilization outcome. Plasma membrane integrity, mitochondrial activity, acrosome integrity, and levels of intracellular reactive oxygen species (ROS) were measured in spermatozoa treated with different concentrations of melatonin. Melatonin-treated spermatozoa were then used for in vitro fertilization, followed by analysis of subsequent embryo development and the expression of apoptosis- and antioxidant-related genes. The results revealed that 10-5 and 10-3 M melatonin led to higher plasma membrane integrity, mitochondrial activity, and acrosome integrity, and significantly decreased intracellular ROS levels (P < 0.05). The blastocyst development rate of in vitro-produced bovine embryos originating from 10-3 M melatonin-treated spermatozoa was significantly higher, while the incidence of apoptotic nuclei in blastocysts was markedly lower than for embryos from any other group (P < 0.05). CASP3 and BAX mRNA abundance were significantly reduced whereas BCL2, XIAP, and CAT transcript abundance were significantly increased in embryos produced from spermatozoa treated with 10-3 M melatonin; GPX4 expression, however, was comparable in all treatment groups. Thus, 10-3 M melatonin can improve the quality of bovine frozen-thawed semen. These beneficial effects appear to influence preimplantation embryos, given the correlation with its anti-apoptotic and anti-oxidative properties. Mol. Reprod. Dev. 83: 993-1002, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27653175 TI - Balancing the risks and benefits of prophylaxis: a reply to "Pneumocystis jiroveci pneumonia in patients treated with systemic immunosuppressive agents for dermatologic conditions". PMID- 27653176 TI - The Thr-His Connection on the Distal Heme of Catalase-Related Hemoproteins: A Hallmark of Reaction with Fatty Acid Hydroperoxides. AB - This review focuses on a group of heme peroxidases that retain the catalase fold in structure, yet show little or no reaction with hydrogen peroxide. Instead of having a role in oxidative defense, these enzymes are involved in secondary metabolite biosynthesis. The prototypical enzyme is catalase-related allene oxide synthase, an enzyme that converts a specific fatty acid hydroperoxide to the corresponding allene oxide (epoxide). Other catalase-related enzymes form allylic epoxides, aldehydes, or a bicyclobutane fatty acid. In all catalases (including these relatives), a His residue on the distal face of the heme is absolutely required for activity. Its immediate neighbor in sequence as well as in 3 D space is conserved as Val in true catalases and Thr in the fatty acid hydroperoxide metabolizing enzymes. Thr-His on the distal face of the heme is critical in switching the substrate specificity from H2 O2 to fatty acid hydroperoxide. PMID- 27653177 TI - Preformed donor-specific HLA antibodies are associated with increased risk of early mortality after liver transplantation. AB - There is limited evidence for a negative impact of preformed, donor-specific HLA antibodies (DSA) identified by cross-matching on outcomes after liver transplantation. Three recent studies have suggested an association between preformed DSA detected by Luminex and reduced graft or recipient survival in liver transplant cohorts with a high prevalence of hepatitis C. This study investigated the impact of preformed DSA identified by Luminex in the Scottish liver transplant population. All recipients of liver transplants in Scotland between 2007 and 2015 with samples available for day of transplant antibody testing and donor HLA typing were included (n=459); 96% of the cohort were white and 19% had a primary diagnosis of hepatitis C. The median follow-up time was 36 months. Preformed DSA were detected in 88 recipients. In multivariate analysis, preformed DSA with a median fluorescent intensity >=10 000 were associated with recipient mortality at 1 year. There was no association between DSA and overall graft or recipient survival. This study adds to the growing body of evidence supporting a detrimental impact of preformed, high-level DSA in a subset of liver transplant recipients by identifying an association in an ethnically and demographically distinct liver transplant population. PMID- 27653178 TI - Long-term vascular effects of anaesthesia in mice - What does it mean for our data and our patients? PMID- 27653179 TI - Osteoclast depletion with clodronate liposomes delays fracture healing in mice. AB - Osteoclasts are abundant within the fracture callus and also localize at the chondro-osseous junction. However, osteoclast functions during fracture healing are not well defined. Inhibition of osteoclast formation or resorptive activity impairs callus remodeling but does not prevent callus formation. Interestingly, though anti-osteoclast therapies differentially affect resolution of callus cartilage into bone. Treatments that inhibit osteoclast formation or viability tend to impair callus cartilage resolution, while treatments that target inhibition of bone resorption generally do not affect callus cartilage resolution. Here, we tested whether depletion of osteoclasts by systemic treatment with clodronate liposomes would similarly impair callus cartilage resolution. ICR mice were treated by intraperitoneal injections of clodronate laden liposomes or control liposomes and subjected to closed femur fracture. Femurs were resected at multiple times after fracture and analyzed by radiography, histology, and mechanical testing to determine effects on healing. Clodronate liposome treatment did not prevent callus formation. However, radiographic scoring indicated that clodronate liposome treatment impaired healing. Clodronate liposome treatment significantly reduced callus osteoclast populations and delayed resolution of callus cartilage. Consistent with continued presence of callus cartilage, torsional mechanical testing found significant decreases in callus material properties after 28 days of healing. The results support a role for osteoclasts in the resolution of callus cartilage into bone. Whether the cartilage resolution role for osteoclasts is limited to simply resorbing cartilage at the chondro-osseous junction or in promoting bone formation at the chondro-osseous junction through another mechanism, perhaps similar to the reversal process in bone remodeling, will require further experimentation. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1699-1706, 2017. PMID- 27653181 TI - High-throughput sequencing to identify microRNA signatures during hepatic differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells. AB - AIM: MicroRNAs (miRNAs) constitute a class of small non-coding RNAs involved in regulation of cognate mRNAs post-transcriptionally. MicroRNAs have been implicated in regulating the stem cell differentiation process. Limited regulatory miRNAs have been reported to date during hepatic differentiation of stem cells. The present study was designed to identify the signature miRNAs implicated in hepatic differentiation of stem cells using next-generation sequencing methods. METHODS: We undertook sequencing of miRNAs isolated from three different time points during hepatic differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUC-MSCs) from two biological replicates. RESULTS: Out of a total known 2588 miRNAs (according to miRBase version 21), 880 miRNAs were identified in our study. A total of 63 significantly expressed miRNAs during hepatic differentiation, with at least 2 fold change and a false discovery rate value <0.05, were considered for further analysis. The putative target genes of significantly downregulated miRNAs during hepatic differentiation appeared to be mostly associated with biological processes that are essential for hepatic differentiation and maintenance of mature hepatic phenotype-like liver development, stem cell differentiation, Wnt receptor signaling pathway, and drug and cholesterol metabolic processes. Putative target genes of significantly upregulated miRNAs are highly enriched in regulating processes that block hepatic differentiation of hUC-MSCs like epithelial-mesenchymal transition, transforming growth factor-beta receptor signaling pathway, and stem cell maintenance. CONCLUSION: The study provides a new insight for investigation of miRNA-regulated pathways during the differentiation process. PMID- 27653180 TI - Pembrolizumab: Role of Modeling and Simulation in Bringing a Novel Immunotherapy to Patients With Melanoma. AB - Recently, immunotherapy has yielded promising results in several cancer types. Contrary to the established classical chemotherapy-dosing paradigm, a maximum tolerated dose approach does not always produce better clinical outcomes for novel targeted therapies, as their efficacy is frequently robust at pharmacologically active doses below the maximum tolerated dose. Integrated safety and efficacy assessments are needed to inform clinical dose and trial design, and to support an early identification of potentially safe and efficacious combination treatments. PMID- 27653182 TI - Senescent Osteocytes: Do They Cause Damage and Can They Be Targeted to Preserve the Skeleton? PMID- 27653183 TI - Does serelaxin treatment alter passive mechanical wall properties in small resistance arteries? AB - The peptide hormone relaxin is recognized for its connective tissue remodeling actions in the reproductive tract during pregnancy and parturition, but it also has vascular remodeling actions independent of pregnancy. Recombinant human relaxin (serelaxin) treatment in male and non-pregnant female rodents enhances passive arterial compliance in the renal vasculature. This review focuses on serelaxin's actions on passive mechanical wall properties in small arteries and highlights the diversity of responses to serelaxin treatment in rodents. Different experimental approaches (duration of serelaxin treatment, rat strain, age) and animal models of disease (obesity, hypertension) will be considered. Most studies in young rodents demonstrate that serelaxin treatment fails to alter passive compliance in resistance-size arteries (mesenteric and femoral arteries and cerebral parenchymal arterioles), suggesting that serelaxin's beneficial effects are minimal in healthy animals. Short-term serelaxin treatment (5d) in aged, obese, and spontaneously hypertensive rats (SHRs) is largely without effect on passive mechanical wall properties. However, a longer duration of serelaxin treatment in SHRs (14d) enhances passive compliance in large muscular arteries as well as resistance-size arteries. In conclusion, serelaxin is capable of vascular remodeling. Its actions are vascular bed-dependent, more prominent in disease, and likely requires a longer duration of treatment to be effective. PMID- 27653184 TI - Simple tests for the diagnosis of childhood obesity: a systematic review and meta analysis. AB - There is a need to accurately quantify levels of adiposity in order to identify overweight and obesity in children. This systematic review aimed to identify all diagnostic accuracy studies evaluating simple tests for obesity and adiposity, including body mass index (BMI), skin-fold thickness and waist circumference, compared against high-quality reference tests. Twenty-four cohort studies including 25,807 children were included. BMI had good performance when diagnosing obesity: a sensitivity of 81.9% (95% confidence interval [CI]: 73.0 to 93.8) for a specificity of 96.0% (95% CI: 93.8 to 98.1). It was less effective at diagnosing overweight (sensitivity: 76.3%, 95% CI: 70.2 to 82.4; specificity: 92.1% 95% CI: 90.0 to 94.3). When diagnosing obesity, waist circumference had similar performance (sensitivity: 83.8%; specificity: 96.5%). Skin-fold thickness had slightly poorer performance (sensitivity: 72.5%; specificity: 93.7%). Few studies considered any other tests. There was no conclusive evidence that any test was generally superior to the others. BMI is a good simple diagnostic test for identifying childhood adiposity. It identifies most genuinely obese and adipose children while misclassifying only a small number as obese. There was no conclusive evidence that any test should be preferred to BMI, and the extra complexity of skin-fold thickness tests does not appear to improve diagnostic accuracy. PMID- 27653185 TI - Standard Gibbs Energy of Metabolic Reactions: I. Hexokinase Reaction. AB - The standard Gibbs energy of reaction enables calculation of the driving force of a (bio)chemical reaction. Gibbs energies of reaction are required in thermodynamic approaches to determine fluxes as well as single reaction conversions of metabolic bioreactions. The hexokinase reaction (phosphorylation of glucose) is the entrance step of glycolysis, and thus its standard Gibbs energy of reaction (DeltaRg degrees ) is of great impact. DeltaRg degrees is accessible from equilibrium measurements, and the very small concentrations of the reacting agents cause usually high error bars in data reduction steps. Even worse, works from literature do not account for the nonideal behavior of the reacting agents (activity coefficients were assumed to be unity); thus published DeltaRg degrees values are not standard data. Consistent treatment of activity coefficients of reacting agents is crucial for the accurate determination of standard Gibbs energy from equilibrium measurements. In this work, equilibrium molalities of hexokinase reaction were measured with an enzyme kit. These results were combined with reacting agents' activity coefficients obtained with the thermodynamic model ePC-SAFT. Pure-component parameters for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were fitted to experimental osmotic coefficients (water + Na2ATP, water + NaADP). DeltaRg degrees of the hexokinase reaction at 298.15 K and pH 7 was found to be -17.83 +/- 0.52 kJ.mol 1. This value was compared with experimental literature data; very good agreement between the different DeltaRg degrees values was obtained by accounting for pH, pMg, and the activity coefficients of the reacting agents. PMID- 27653186 TI - The accuracy of claims data for measuring transfusion rates. AB - OBJECTIVE: To determine if billing records accurately report the receipt of red blood cell transfusions. BACKGROUND: Many red blood transfusions are given inappropriately, but efforts to monitor transfusion rates are hampered by a lack of data that facilitate benchmarking. METHODS: Using billing records and electronic medical records from 53 community hospitals, we estimated the sensitivity and specificity of billing records for measuring the receipt of transfusions in patients undergoing surgery for hip fractures. RESULTS: The sample included 12 091 patients, of whom 5215 received red blood cell transfusions according to electronic medical records. The sensitivity of billing data for measuring transfusions was 71.6% (95% CI: 60.4-82.8%). The specificity was 92.6% (95% CI: 88.3-97.0%). CONCLUSIONS: Researchers can use billing records to measure transfusion rates but should consider excluding hospitals with very low transfusion rates, which may indicate that the hospitals do not accurately report transfusions in billing data. PMID- 27653187 TI - Reverse Size Dependences of the Cellular Uptake of Triangular and Spherical Gold Nanoparticles. AB - Gold nanoparticles (GNPs) show promise as both drug and imaging carriers with applications in both diagnosis and therapy. For the safe and effective use of such gold nanomaterials in the biomedical field, it is crucial to understand how the size and shape of the nanomaterials affect their biological features, such as in vitro cellular uptake speed and accumulation as well as cytotoxicity. Herein, we focus on triangular gold nanoparticles (TNPs) of four different sizes (side length 46, 55, 72, and 94 nm; thickness 30 nm) and compare the cellular internalization efficiency with those of spherical nanoparticles (SNPs) of various diameters (22, 39, and 66 nm). Both surfaces were coated with anionic thiol ligands. Inductively coupled plasma-emission spectrometry (ICP-ES) data demonstrated that TNPs with longer sides showed higher levels of uptake into RAW264.7 and HeLa cells. On the other hand, in the case of SNPs, those with smaller diameters showed higher levels of uptake in both cells. Our results support the notion of a reverse size dependence of TNPs and SNPs in terms of cellular uptake. For HeLa cells, in particular, 20-fold more efficient internalization was observed for TNPs with longer sides (72 nm side length) compared to SNPs (66 nm) with a similar surface area. These results highlight the importance of the shape of nanomaterials on their interactions with cells and provide a useful guideline for the use of TNPs. PMID- 27653188 TI - Validity of wrist worn accelerometers and comparability between hip and wrist placement sites in estimating physical activity behaviour in preschool children. AB - Wrist-worn accelerometers can increase compliance with wearing accelerometers, however, several large scale studies continue to use hip-worn accelerometers and it is unclear how comparable data is from the two sites. The study aims were: to investigate agreement between wrist- and hip- worn accelerometers and to determine the validity of Johansson et al cut-points for wrist worn accelerometers in preschool children. A sample of 32 preschool children (21 boys, 4.2 (0.5) years, BMI 16.6 (1.1)) were videoed wearing GT3X+ accelerometers on their wrist and hip while they engaged in 1 h of free-play in their nursery. Children's activity were coded using, the children's activity rating scale (CARS): with CARS, level 1 'sedentary' and levels 2-5 were classified as time spent in total physical activity (TPA). Accelerometry data were processed using Johansson et al cut-points for the wrist data and Evenson et al cut-points for the hip data, into time spent in different intensities of physical activity (PA). The mean counts per minute (cpm) from the hip and wrist were compared. There was a strong correlation between the hip and wrist cpm (r = 0.81, p < 0.01) and total count data (r = 0.83 p < 0.01), however there was a large systematic bias with wide limits of agreement. Good agreement (mean difference (LOA) 1.1 ( 9.9, 12.1) was found between the CARS estimate of TPA (29.5 (10.4) mins) and the wrist estimate, using the Johansson et al cut points (28.4 (9.8) mins). There was also a reasonable agreement between the hip estimates with the Evenson et al cut points and Johansson et al estimate (mean difference (LOA):6.3 (-8.8, 21.4) mins. In conclusion, the findings suggest that the Johansson et al (2013 Pediatr. Obes. 10 1-6) cut-points applied to wrist worn accelerometers provides a valid estimate of TPA in preschool children and have reasonable agreement with Evenson et al cut points applied to hip accelerometers. PMID- 27653189 TI - Chemotherapy-induced cardiotoxicity: importance of early detection. PMID- 27653190 TI - Technological trends and market perspectives for production of microbial oils rich in omega-3. AB - In recent years, foods that contain omega-3 lipids have emerged as important promoters of human health. These lipids are essential for the functional development of the brain and retina, and reduction of the risk of cardiovascular and Alzheimer's diseases. The global market for omega-3 production, particularly docosahexaenoic acid (DHA), saw a large expansion in the last decade due to the increasing use of this lipid as an important component of infant food formulae and supplements. The production of omega-3 lipids from fish and vegetable oil sources has some drawbacks, such as complex purification procedures, unwanted contamination by marine pollutants, reduction or even extinction of several species of fish, and aspects related to sustainability. A promising alternative system for the production of omega-3 lipids is from microbial metabolism of yeast, fungi, or microalgae. The aim of this review is to discuss the various omega-3 sources in the context of the global demand and market potential for these bioactive compounds. To summarize, it is clear that fish and vegetable oil sources will not be sufficient to meet the future needs of the world population. The biotechnological production of single-cell oil comes as a sustainable alternative capable of supplementing the global demand for omega-3, causing less environmental impact. PMID- 27653191 TI - Stable, Free-space Optical Trapping and Manipulation of Sub-micron Particles in an Integrated Microfluidic Chip. AB - We demonstrate stable, free-space optical trapping and manipulation in an integrated microfluidic chip using counter-propagating beams. An inverted ridge type waveguide made of SU8 is cut across by an open trench. The design of the waveguide provides low propagation losses and small divergence of the trapping beam upon emergence from the facet, and the trench designed to be deeper and wider than the optical mode enables full utilization of the optical power with an automatic alignment for counter-propagating beams in a trap volume away from all surfaces. After integration with polydimethylsiloxane (PDMS) microfluidic channel for particle delivery, 0.65 MUm and 1 MUm diameter polystyrene beads were trapped in free space in the trench, and manipulated to an arbitrary position between the waveguides with a resolution of < 100 nm. Comparison with numerical simulations confirm stable trapping of sub-micron particles, with a 10 kBT threshold power of less than 1 mW and a stiffness that can be 1 order of magnitude larger than that of comparable fiber-based trapping methods. PMID- 27653192 TI - [Development and validation of indicators for best patient safety practices: the ISEP-Brazil Project]. AB - Efficacious patient safety monitoring should focus on the implementation of evidence-based practices that avoid unnecessary harm related to healthcare. The ISEP-Brazil project aimed to develop and validate indicators for best patient safety practices in Brazil. The basis was the translation and adaptation of the indicators validated in the ISEP-Spain project and the document Safe Practices for Better Healthcare (U.S. National Quality Forum), recommending 34 best practices. A 25-member expert panel validated the indicators. Reliability and feasibility were based on a pilot study in three hospitals with different management formats (state, federal, and private). Seventy-five best practice indicators were approved (39 structure; 36 process) for 31 of the 34 recommendations. The indicators were considered valid, reliable, and useful for monitoring patient safety in Brazilian hospitals. PMID- 27653193 TI - [Neonatal adverse events and near misses reported in Brazil from 2007 to 2013]. AB - This study aimed to analyze adverse events and near misses in newborns up to 28 days of life, reported to the Brazilian National Notification System for Sanitary Surveillance (NOTIVISA) system from 2007 to 2013. This was a quantitative, descriptive, retrospective study with analysis of secondary data. A total of 355 incidents were reported: 118 (33.3%) related to medical devices, 4 (1.1%) medical equipment, and 233 (65.6%) medicines. Silver nitrate and antibiotics were the most frequently reported medicines, and among medical devices and equipment, phlebitis associated with IV lines was the most frequently reported adverse event. The study unveils the reporting of adverse events and near misses, fostering discussion on what actually constitutes harm according to the person that reports the event. The challenge for NOTIVISA is to improve the system, and as with other information systems, this results from its use, critical analysis, and interaction with users - incident reporters and interested parties like teaching and research institutions. PMID- 27653194 TI - [Effectiveness of the National Strategy for Healthy Complementary Feeding to improve complemantary feeding of infants in a municipality in Southern Brazil]. AB - The aim of this study was to assess the effectiveness of the National Strategy for Healthy Complementary Feeding (ENPACS) in improving complementary feeding in the first year of life in a Brazilian municipality (county). This was an impact evaluation study that enrolled 340 infants from 6 to 12 months of age, followed at primary healthcare units. The target outcomes were prevalence rates for the consumption of vegetables, legumes, fruits, and unhealthy foods, and the prevalence of foods with adequate consistency for age. Poisson regression showed that the strategy was associated with reductions of 32% in the consumption of sodas and/or industrialized juices, 35% of industrialized foods, and 5% of unhealthy foods. There was no increase in the consumption of fruits, legumes, vegetables, or foods with adequate consistency for age. In conclusion, the strategy's positive effect was partial, but it has the potential to help improve infant nutrition, based on its effectiveness in reducing the consumption of unhealthy foods. PMID- 27653195 TI - [Watching TV and eating habits: the results from 2006 to 2014 in Brazilian state capitals]. AB - The objectives were to analyze trends in TV watching in Brazil and to identify the association between this habit and food consumption in the Brazilian adult population from 2006 to 2014. Data were obtained from the Surveillance System for Risk and Protective Factors for Chronic Illnesses Using a Telephone Survey (VIGITEL) for the years 2006 to 2014. The daily habit of watching TV and consumption of fruits, vegetables, beans, meat, milk, sodas, and/or sweetened beverages were analyzed over the period, and their association was investigated using regression models. The proportion of adults that reported watching more than three hours of TV per day did not vary significantly over the years, but these individuals showed declining consumption of healthy foods and increasing consumption of unhealthy foods. This situation was observed in both sexes and in all age and schooling brackets. The habit of watching TV is associated with unhealthy eating. PMID- 27653196 TI - [Environmental, social, and roadway vulnerability in accidents involving transportation of hazardous products: a case study of the BR-101 highway between Osorio and Torres in Rio Grande do Sul State, Brazil]. AB - This study aimed to assess the environmental and social vulnerability and identify critical highway stretches for accidents involving transportation of hazardous products on the BR-101 highway between the cities of Osorio and Torres in Rio Grande do Sul State, Brazil. The study's approach consisted of a multiple criteria analysis combining highway safety analysis and environmental and social vulnerability analysis in the occurrence of accidents with hazardous products, plus cartographic analysis techniques. Thirty-eight kilometers of the highway showed high vulnerability, of which 8 kilometers with critical vulnerability, associated with bridges over rivers, water uptake points, a tunnel, environmental preservation areas, and an urban area. These stretches should be prioritized when developing action plans for accident mitigation and development of public policies for this highway. This proved to be an unprecedented approach when compared to existing studies and a potentially useful tool for decision-making in emergency operations. PMID- 27653197 TI - [Association between malaria and anemia in an urban area with Plasmodium transmission: Mancio Lima, Acre State, Brazil]. AB - The aim of this study was to analyze the prevalence of malaria-attributable anemia in the urban population of Mancio Lima, Acre State, Brazil. This was a non concurrent cohort study of 1,167 persons followed for the three months prior to the interview using data from the SIVEP-Malaria database. Anemia frequency and prevalence rates were calculated in patients with and without a recent history of malaria, according to target variables. 50.2% of the individuals were males, and 67.96% were 15 years or older. Overall anemia prevalence was 7.1%, higher in the 6 months to 5 years age bracket. Some 8.3% of men with a recent history of malaria presented anemia. Overall, prevalence of malaria-attributable anemia was negligible, except in men (2.4%) and the Cobal neighborhood (51.4%). The results showed that anemia prevalence was low and that malaria's contribution to anemia only existed in men and in specific geographic areas. PMID- 27653198 TI - [Analysis of researchers' implication in a research-intervention in the Stork Network: a tool for institutional analysis]. AB - This qualitative study is based on institutional analysis as the methodological theoretical reference with the objective of analyzing researchers' implication during a research-intervention and the interferences caused by this analysis. The study involved researchers from courses in medicine, nursing, and dentistry at two universities and workers from a Regional Health Department in follow-up on the implementation of the Stork Network in Sao Paulo State, Brazil. The researchers worked together in the intervention and in analysis workshops, supported by an external institutional analysis. Two institutions stood out in the analysis: the research, established mainly with characteristics of neutrality, and management, with Taylorist characteristics. Differences between researchers and difficulties in identifying actions proper to network management and research were some of the interferences that were identified. The study concludes that implication analysis is a powerful tool for such studies. PMID- 27653199 TI - [Evaluation of the cascade of care in prevention of mother-to-child HIV transmission in Brazil]. AB - This study aimed to assess the cascade of care in the reduction of mother-to child HIV transmission in the states of Amazonas, Ceara, Espirito Santo, Rio de Janeiro, and Rio Grande do Sul and the Distrito Federal, Brazil, using data from the Brazilian Information System on Diseases of Notification (SINAN). From 2007 to 2012, there was an increase (from 7.3% in Distrito Federal to 46.1% in Amazonas) in intra-gestational detection of HIV in 5 states, with a 18.6% reduction in Rio de Janeiro. Fewer than 90% of the women received antiretroviral therapy during their prenatal care, including those that already knew they were HIV-positive. The elective cesarean rate was low. The AIDS detection rate in children under 5 years as a proxy for mother-to-child HIV transmission showed a reduction of 6.3% from 2007 to 2012, and was highest in Rio Grande do Sul (50%), the state with the highest rates in the period, while Espirito Santo showed the highest increase (50%). Evaluation of the cascade of HIV care in pregnant women identified flaws in all the points. A link is needed between primary care and referral centers for HIV/AIDS, organizing care for the family and better outcomes for the children. PMID- 27653200 TI - [Psychosocial stressors, sense of community, and subjective wellbeing in children and adolescents in urban and rural areas in Northeast Brazil]. AB - The study's overall objective was to investigate the relationship between psychosocial stressors, sense of community, and subjective wellbeing in urban and rural schoolchildren in Northeast Brazil, focusing on differences according to territorial context. The sample consisted of 757 participants, 495 from urban schools and 262 from rural schools, enrolled in the 6th and 7th grades (9 to 18 years of age) in 21 municipal and state public schools, of which 13 urban and 8 rural, in 7 municipalities (counties) in Ceara State, Brazil. The study instruments were inventory of stressful events, scale of life satisfaction for students, index of sense of community, and satisfaction indices by life domains (family, material goods, relations, neighborhood/zone, health, time, school, and personal). The results indicate that socioeconomically underprivileged public schoolchildren from urban areas are more exposed to daily stress and score lower on satisfaction in specific domains of life and on sense of community. This latter is an important indicator for evaluating wellbeing in this young population. PMID- 27653201 TI - ["Hormone bomb": risks of emergency contraception from the perspective of pharmacy attendants in Rio de Janeiro, Brazil]. AB - This study focused on views towards emergency contraception among pharmacy attendants in Greater Metropolitan Rio de Janeiro, Brazil. The empirical material came from a socio-anthropological study with 20 semi-structured interviews of pharmacy attendants of both sexes (8 females and 12 males). The interviews showed negative views of emergency contraception, emphasizing its potential health risks. Interviews considered emergency contraception a "hormone bomb" that can harm the female reproductive organs and other organ systems. The pharmacy attendants highlighted the risks of "uncontrolled" or "indiscriminate" use, especially by adolescents and young women. Since they considered it "dangerous" to women's bodies, they assigned the responsibility for orientation and counseling on use of the method to gynecologists rather than to pharmacists. The article discusses the need to expand the public debate on emergency contraception in Brazil to include pharmacists and pharmacy attendants, in addition to health professionals in general and teachers. PMID- 27653202 TI - [Collective memories of women who have experienced maternal near miss: health needs and human rights]. AB - The collective memories of women that have experienced maternal near miss can help elucidate serious obstetric events, like maternal death. Their experience is authentic and representative, with the construction of a common identity. This identity lends quality to a group's memory, and such memory is thus a social phenomenon. The study analyzed the experience of twelve women who nearly died during the gestational and postpartum cycle. The thematic oral history method was used, from the perspective of health needs and human rights. Six collective memories comprised the discourses: unmet health needs; healthcare deficiencies; denial of contact with the newborn child; violation of rights; absence of demand for rights; and compensation for unmet rights and needs. To understand these women's health needs is to acknowledge the women as bearers of rights and to individualize care, respecting their autonomy, guaranteeing access to technologies, and establishing an effective bond with health professionals. PMID- 27653203 TI - [Health and school: thoughts on the medicalization of education]. AB - Children and youth reach school with different starting points. It is not known for sure how far these children and youth will go, and what path the school holds for them, particularly at a stage in which teachers are divided in multi-tasking (with some tasks that are merely administrative). Meanwhile, it is increasingly common to explain students' "inappropriate" behavior in biomedical terms. The increasing emergence of disorders and deficits calls for critical reflection on what they actually involve in public health terms. Thisarticle addresses the school's role in the educational achievement and comprehensive development of students flagged for or with clinical indication of medication based on "fuzzy" diagnoses. The concept of medicalization acquires a central position, and the article discusses its implications based on a set of field notes and interviews with parents and teachers in the North of Portugal. PMID- 27653204 TI - What CSP expects of systematic reviews in the future. PMID- 27653206 TI - Erratum: High current density GaAs/Si rectifying heterojunction by defect free Epitaxial Lateral overgrowth on Tunnel Oxide from nano-seed. PMID- 27653205 TI - Factors Affecting Sexual Activity in Midlife Women: Results from the Midlife Health Study. AB - BACKGROUND: The objective of this study was to identify (1) the importance of a number of potential factors affecting the likelihood of sexual activity in perimenopausal women and (2) the likelihood of a number of barriers to sexual activity. METHODS: A cohort of 780 women undergoing menopausal transition was surveyed annually for up to 7 years. Data were collected on sexual activity and, if not sexually active, reasons for no sexual activity, as well as a number of potential risk factors. Height and weight were measured at an annual clinic visit; serum hormone concentrations were assayed using blood samples donated annually. Data were examined with logistic regression models using the individual as a random effect, with subset analysis of nonsexually active women to determine the likelihood of each barrier. All factors with univariate associations of p < 0.1 were considered in multivariate model building with stepwise addition. RESULTS: A total of 2440 woman-years were included in the analysis of sexual activity. The likelihood of sexual activity increased for women living with a partner, with perceived quality of life, and with less frequent hot flashes. Among 513 woman-years reporting no sexual activity, women living with a partner and women reporting frequent fatigue were less likely to lack a sexual partner, but were more likely to have sexual difficulties. Women with more physical work than average and women with higher serum estradiol levels were less likely to have sexual difficulties. CONCLUSIONS: The factors associated with sexual activity in menopausal women are complex, indicating that an individualized approach to improving sexual activity is required. PMID- 27653208 TI - Attention and interpretation processes and trait anger experience, expression, and control. AB - This study explored attention and interpretation biases in processing facial expressions as correlates of theoretically distinct self-reported anger experience, expression, and control. Non-selected undergraduate students (N = 101) completed cognitive tasks measuring attention bias, interpretation bias, and Spielberger's State-Trait Anger Expression Inventory (STAXI-2). Attention bias toward angry faces was associated with higher trait anger and anger expression and with lower anger control-in and anger control-out. The propensity to quickly interpret ambiguous faces as angry was associated with greater anger expression and its subcomponent of anger expression-out and with lower anger control-out. Interactions between attention and interpretation biases did not contribute to the prediction of any anger component suggesting that attention and interpretation biases may function as distinct mechanisms. Theoretical and possible clinical implications are discussed. PMID- 27653207 TI - Increased aqueous flare is associated with thickening of inner retinal layers in eyes with retinitis pigmentosa. AB - Retinitis pigmentosa(RP) is a hereditary retinal disease that causes photoreceptor, outer retinal, degeneration. Although the pathogenesis is still unclear, there have been numerous reports regarding inner retinal changes in RP eyes. The aim of this study is to retrospectively evaluate the changes in the thicknesses of different retinal layers of RP eyes, and its association with aqueous flare, which is used for measuring the intensity of intraocular inflammation. A total of 125 eyes of 64 patients with RP and 13 normal eyes were studied. The thicknesses of total neural retina,nerve fiber layer(NFL),ganglion cell layer(GCL),inner plexiform layer(IPL),inner nuclear layer(INL),outer layers and foveal thickness were measured in the optical coherence tomographic images. Aqueous flare was measured with a laser flare-cell meter. The associations between those parameters, visual acuity and visual field were determined in RP eyes using multivariate analysis. The results of this study showed the significant thickening of NFL, GCL and INL, the significant thinning of outer layers and the association of them with increased aqueous flare, whereas NFL and INL thickening associated with outer retinal thinning. These results can suggest the involvement of intraocular inflammation in the pathogenesis of inner retinal thickening as a secondary change following outer retinal degeneration. PMID- 27653209 TI - Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs. AB - Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19 depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19. PMID- 27653210 TI - An improved in vitro method for screening toxin and medicine targeting CYP2E1. AB - The cytochrome P450 enzyme 2E1 (CYP2E1) presents in both microsome and mitochondrion, which influences the metabolism of many xenobiotics. The mice active liver homogenate was prepared for the medicinal incubation and mitochondrion was extracted for chemical screening targeting CYP2E1 enzyme. Representative CYP2E1 inducers (ethanol and pyrazole) and inhibitors (diallyldisulfide and kaempferol) were applied to evaluate the effectiveness of homogenate-mitochondrial system. In parallel, the in-vitro microsomal method targeting CYP2E1 was also operated for comparison. The results showed that in homogenate-mitochondrial method, the protein level and activity of CYP2E1 were increased by ethanol and pyrazole; reduced by diallyldisulfide and kaempferol, and this homogenate-mitochondrial method is convenient with good repeatability and reproducibility in screening chemicals targeting CYP2E1, especially for the inducers. Thus, the homogenate-mitochondrial method might be effective in screening both CYP2E1 inhibitor and inducer. PMID- 27653211 TI - The effects of chlormequat chloride on the development of pubertal male rats. AB - Chlormequat Chloride (CCC) is a plant growth regulator that is widely applied in agriculture. Previous studies have shown that long-term exposure of CCC could decrease body weight in animals. However, the underlying mechanisms have not been studied. In this study, CCC was administered to rats daily by gavage on postnatal days 23-60 at doses of 0, 75, 150 and 300mg/kg bw/d. The results showed that body weight and the length of the right femur were significantly decreased in the 300mg/kg bw/d group. Histological analysis of proximal growth plates of the right femurs showed narrowed proliferative zones and hypertrophic zones in CCC-treated groups. The mRNA expression of growth hormone, growth hormone receptor and insulin like growth factor 1 were decreased in the CCC-treated group. The results indicated that CCC may affect the expression of growth hormone and insulin-like growth factor 1 and subsequently cause a decrease in body weight and bone length. PMID- 27653212 TI - Screening, brief intervention, and referral to treatment: a 5-year comparison of staff buy-in. PMID- 27653214 TI - Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers. AB - CONTEXT: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system. OBJECTIVE: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats. MATERIAL AND METHODS: Animals were randomized into control, kernel extract (100 and 200 mg/kg/d, orally), dexamethasone (0.03 mg/kg/d, subcutaneously), dexamethasone + kernel (100 and 200 mg/kg/d, separately), and dexamethasone + captopril (25 mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX). RESULTS: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128 +/- 7 vs. 105 +/- 3 mmHg, p < 0.05 and 0.2 +/- 0.046 vs. 0.08 +/- 0.02, p < 0.05). Combination of dexamethasone and walnut (200 mg/kg) prevented the dexamethasone-induced diastolic hypertension (109 +/- 3 vs. 128 +/- 7 mmHg; p < 0.05), increased the GPX level (14.8 +/- 1.46 vs. 5.1 +/- 0.64 unit/mg, p < 0.05), reduced the MDA/GPX ratio (0.16 +/- 0.015 vs. 0.2 +/- 0.046) and improved serum NO level. CONCLUSION: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production. PMID- 27653213 TI - Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome. AB - Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCbeta1 palmitoylation and signalling activity, effects significantly reduced in Zdhhc21dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCbeta1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCbeta1 palmitoylation in endothelial inflammation. PMID- 27653215 TI - Reformulations of practice: beyond experience in paramedic airway management. AB - OBJECTIVE: "Deliberate practice" and "feedback" are necessary for the development of expertise. We explored clinical performance in settings where these features are inconsistent or limited, hypothesizing that even in algorithmic domains of practice, clinical performance reformulates in ways that may threaten patient safety, and that experience fails to predict performance. METHODS: Paramedics participated in two recorded simulation sessions involving airway management, which were analyzed three ways: first, we identified variations in "decision paths" by coding the actions of the participants according to an airway management algorithm. Second, we identified cognitive schemas driving behavior using qualitative descriptive analysis. Third, clinical performances were evaluated using a global rating scale, checklist, and time to achieve ventilation; the relationship between experience and these metrics was assessed using Pearson's correlation. RESULTS: Thirty participants completed a total of 59 simulations. Mean experience was 7.2 (SD=5.8) years. We observed highly variable practice patterns and identified idiosyncratic decision paths and schemas governing practice. We revealed problematic performance deficiencies related to situation awareness, decision making, and procedural skills. There was no association between experience and clinical performance (Scenario 1: r=0.13, p=0.47; Scenario 2: r=-0.10, p=0.58), or the number of errors (Scenario 1: r=.10, p=0.57; Scenario 2: r=0.25, p=0.17) or the time to achieve ventilation (Scenario 1: r=0.53, p=0.78; Scenario 2: r=0.27, p=0.15). CONCLUSION: Clinical performance was highly variable when approaching an algorithmic problem, and procedural and cognitive errors were not attenuated by provider experience. These findings suggest reformulations of practice emerge in settings where feedback and deliberate practice are limited. PMID- 27653216 TI - Metrics in academic profiles: a new addictive game for researchers? AB - This study aims to promote reflection and bring attention to the potential adverse effects of academic social networks on science. These academic social networks, where authors can display their publications, have become new scientific communication channels, accelerating the dissemination of research results, facilitating data sharing, and strongly promoting scientific collaboration, all at no cost to the user.One of the features that make them extremely attractive to researchers is the possibility to browse through a wide variety of bibliometric indicators. Going beyond publication and citation counts, they also measure usage, participation in the platform, social connectivity, and scientific, academic and professional impact. Using these indicators they effectively create a digital image of researchers and their reputations.However, although academic social platforms are useful applications that can help improve scientific communication, they also hide a less positive side: they are highly addictive tools that might be abused. By gamifying scientific impact using techniques originally developed for videogames, these platforms may get users hooked on them, like addicted academics, transforming what should only be a means into an end in itself. PMID- 27653217 TI - Hypolipidemic effects of crude green tea polysaccharide on rats, and structural features of tea polysaccharides isolated from the crude polysaccharide. AB - Crude tea polysaccharide (crude TPS) was prepared from instant green tea by ethanol precipitation followed by ultrafiltration membrane treatment and its effects on blood lipid, liver lipid, and fecal lipid levels were examined with Sprague-Dawley rats fed a high-fat diet. Although crude TPS showed no effects on the serum lipid levels, it suppressed the liver lipid accumulation and increased the fecal excretion of dietary fat. Then, the structural features of crude TPS were investigated. After separation of crude TPS by DEAE-cellulose and gel filtration column chromatography, two kinds of neutral tea polysaccharides (NTPS LP and NTPS-HH) and an acidic polysaccharide (ATPS-MH) were obtained. According to monosaccharide composition, methylation, and NMR analyses, NTPS-LP, NPTS-HH, and ATPS-MH were presumed to be starch, arabinogalactan with beta-1,3-linked galactosyl backbone blanched at position 6 and with 1,5-linked arabinofuranosyl residues, and alpha-1,4-linked galacturonic acid backbone with arabinogalactan region, respectively. PMID- 27653218 TI - The Substrate is a pH-Controlled Second Gate of Electrolyte-Gated Organic Field Effect Transistor. AB - Electrolyte-gated organic field-effect transistors (EGOFETs), based on ultrathin pentacene films on quartz, were operated with electrolyte solutions whose pH was systematically changed. Transistor parameters exhibit nonmonotonic variation versus pH, which cannot be accounted for by capacitive coupling through the Debye Helmholtz layer. The data were fitted with an analytical model of the accumulated charge in the EGOFET, where Langmuir adsorption was introduced to describe the pH dependent charge buildup at the quartz surface. The model provides an excellent fit to the threshold voltage and transfer characteristics as a function of the pH, which demonstrates that quartz acts as a second gate controlled by pH and is mostly effective from neutral to alkaline pH. The effective capacitance of the device is always greater than the capacitance of the electrolyte, thus highlighting the role of the substrate as an important active element for amplification of the transistor response. PMID- 27653220 TI - HDL infusion for the management of atherosclerosis: current developments and new directions. AB - PURPOSE OF REVIEW: Because human genetic studies and large clinical trials have demonstrated that HDL-cholesterol levels are not causally related to cardiovascular disease risk, attention has shifted toward the functional properties of HDL. Infusion of HDL mimetics containing apolipoprotein A-I remains a potential strategy to exploit the atheroprotective effects of HDL. RECENT FINDINGS: Three HDL mimetic drugs are under development and currently being evaluated in clinical trials. Upon infusion, these drugs increase cholesterol efflux capacity. Although proof-of-concept studies are promising, large outcome studies are awaited. Alternatively, HDL particles may be used for targeted drug delivery in a nanomedicine approach. Finally, links between cholesterol efflux and myelopoeisis may prove to be a target for HDL infusion in the future. SUMMARY: Clinical studies are currently ongoing to evaluate the potential of several HDL mimetic drugs. Novel nanomedicinal approaches and emerging pathophysiological insights may further expand the relevance of HDL infusion. PMID- 27653219 TI - The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes. AB - The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology. PMID- 27653221 TI - Absence of Neuropathology With Prolonged Isoflurane Sedation in Healthy Adult Rats. AB - BACKGROUND: The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation. METHODS: Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with alpha-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7. RESULTS: Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged. CONCLUSIONS: No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology. PMID- 27653223 TI - Angiotensin Neprilysin Inhibition for Patients With Heart Failure: What If Sacubitril/Valsartan Were a Treatment for Cancer? PMID- 27653224 TI - A Reversible Cause of Left Ventricular Dysfunction. PMID- 27653222 TI - A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients. AB - BACKGROUND: Dexamethasone is reported to induce both tumor-suppressive and tumor promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. METHODS: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. RESULTS: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included "role of breast cancer 1 in DNA damage response" (P=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and -3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing "stem-like" cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. CONCLUSIONS: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID- 27653225 TI - Outcomes of Patients Undergoing Endoscopic Endonasal Skull Base Surgery at a VA Hospital. PMID- 27653226 TI - Comparative Study of the Immunoregulatory Capacity of In Vitro Generated Tolerogenic Dendritic Cells, Suppressor Macrophages, and Myeloid-Derived Suppressor Cells. AB - BACKGROUND: Regulatory myeloid cell (RMC) therapy is a promising strategy for the treatment of immunological disorders such as autoimmune disease and allograft transplant rejection. Various RMC subsets can be derived from total bone marrow using different protocols, but their phenotypes often overlap, raising questions about whether they are truly distinct. METHODS: In this study, we directly compared the phenotype and function of 3 types of RMCs, tolerogenic dendritic cells, suppressor macrophages, and myeloid-derived suppressor cells, generated in vitro from the same mouse strain in a single laboratory. RESULTS: We show that the 3 RMC subsets tested in this study share some phenotypic markers, suppress T cell proliferation in vitro and were all able to prolong allograft survival in a model of skin transplantation. However, our results highlight distinct mechanisms of action that are specific to each cell population. CONCLUSIONS: This study shows for the first time a side-by-side comparison of 3 types of RMCs using the same phenotypic and functional assays, thus providing a robust analysis of their similarities and differences. PMID- 27653228 TI - Influence of Donor and Recipient CYP3A4, CYP3A5, and ABCB1 Genotypes on Clinical Outcomes and Nephrotoxicity in Liver Transplant Recipients. AB - BACKGROUND: This study investigated the influence of the CYP3A4*22, CYP3A5*3, and ABCB1 exons 12, 21, and 26 polymorphisms in donors and recipients on clinical outcomes and renal function in 170 liver transplant patients on cyclosporin A (CsA) or tacrolimus (Tac). METHODS: Allelic discrimination assays were used for genotyping. Multivariate time-dependent Cox proportional hazard models, multiple linear regression using the generalized estimating equation and linear mixed effect models were used for statistical analysis. RESULTS: Expression of CYP3A5 by either or both the donor and the recipient was significantly associated with lower Tac, but not CsA, dose-normalized trough levels. In the whole population, graft loss was only significantly associated with longer exposure to high calcineurin inhibitor (CNI) concentrations (hazard ratio, 6.93; 95% confidence interval, 2.13-22.55), P = 0.00129), whereas in the Tac subgroup, the risk of graft loss was significantly higher in recipient CYP3A5*1 expressers (hazard ratio, 3.39; 95% confidence interval, 1.52-7.58; P = 0.0028). Renal function was significantly associated with: (1) baseline modification of diet in renal disease (beta = 0.51 +/- 0.05; P < 0.0001); (2) duration of patient follow-up (per visit, beta = -0.98 +/- 0.22; P < 0.0001); and (3) CNI exposure (per quantile increase, beta = -2.42 +/- 0.59; P < 0.0001). No genetic factor was associated with patient survival, acute rejection, liver function test results, recurrence of viral or other initial liver disease, or renal function. CONCLUSIONS: This study confirms the effect of CYP3A5*3 on tacrolimus dose requirement in liver transplantation and shows unexpected associations between the type of, and exposure to, CNI and either chronic rejection or graft loss. None of the genetic polymorphisms studied had a noticeable impact on renal function degradation at 10 years. PMID- 27653229 TI - Controlling Diabetes After Liver Transplantation: Room for Improvement. AB - BACKGROUND: Diabetes mellitus is a chronic illness with great impact on long-term outcome after liver transplantation (LT). Despite this, the current level of glycemic control and quality of screening strategies for diabetes-associated conditions that are being provided to liver transplant recipients with diabetes have not yet been assessed. METHODS: We performed a cross-sectional, multicenter study that included 344 liver transplant recipients and examined the level of glycemic control and its associated factors, as well as the quality of screening strategies for diabetes-associated conditions. RESULTS: Seventy-five patients (21.8%) suffered from diabetes before transplantation, and 82 (23.8%) developed diabetes mellitus after transplantation. Adequate glycemic control (HbA1c < 7%) was achieved in 66.7% of the patients. Forty-eight percent of patients underwent regular screening for retinopathy, 47.1% for nephropathy, 4.5% for neuropathy, and 5.7% for foot ulcers. Diabetes was associated with higher frequency of cardiovascular disease and dyslipidemia both before and after LT. Multivariate analysis revealed association between poor glycemic control and arterial hypertension, presence of diabetes before transplantation, elevated GGT, and insulin use. CONCLUSIONS: Glycemic control was inadequate in 33.3% of LT recipients with diabetes, and screening protocols for diabetes-associated conditions did not meet the standards for medical care set by the American Diabetes Association in any of the participating centers. Consequently, this study reveals a clear deficiency in the quality of diabetes care provided to patients after LT and, hence, we predict that future progress in this area will have a significant impact on medium-term to long-term outcome of these patients. PMID- 27653230 TI - Metal/Benzoyl Peroxide (BPO)-Controlled Chemoselective Cycloisomerization of (o Alkynyl)phenyl Enaminones: Synthesis of alpha-Naphthylamines and Indeno[1,2 c]pyrrolones. AB - Synthetic methods involving chemoselective tandem reactions for the synthesis of alpha-naphthylamines and indeno[1,2-c]pyrrolones starting from (o-aklynyl)phenyl enaminones are described. When reactions were carried out in N,N dimethylformamide (DMF) using a AgNO3 catalyst, alpha-naphthylamines were obtained in up to 89% isolated yields within 2 h. Whereas indeno[1,2-c]pyrrolones were produced in high isolated yields in the presence of benzoyl peroxide (BPO) and CuCl catalysis. PMID- 27653227 TI - Adherence to and Acceptance of Once-Daily Tacrolimus After Kidney and Liver Transplant: Results From OSIRIS, a French Observational Study. AB - BACKGROUND: Adherence to immunosuppressive treatments is a major concern in transplanted patients. METHODS: This 6-month French observational, longitudinal, prospective study aimed to assess patient adherence to and acceptance of once daily tacrolimus (Advagraf) initiation in kidney and liver transplant recipients. Data from 1106 patients initiating once-daily tacrolimus during posttransplant follow-up were analyzed. Adherence and acceptance were assessed using self administered questionnaires at inclusion and at 3 and 6 months. RESULTS: Mean age was 52.4 +/- 13.2 years, 61.5% were men. For 94.9% of patients, once-daily tacrolimus was prescribed after switching from twice-daily tacrolimus. At inclusion, 20.9% of patients reported good treatment adherence, 72.0% minor nonadherence, and 7.1% were nonadherent. Mean general acceptance score (range, 0 100) was 77.7 (+/-24.7). At 3 months, adherence was improved in 21.1%, unchanged in 69.2%, and worsened in 9.7% of patients. Mean general acceptance score was 75.4 (+/-26.5). General acceptance score was improved in 28.0%, unchanged in 39.4%, and worsened in 32.7% of patients. At 6 months, similar changes in adherence and acceptance were observed. Higher general acceptance score at month 3 was significantly associated with better adherence at month 6. CONCLUSIONS: Conversion to once-daily tacrolimus led to an improved rate of adherence at month 3 in more than 20% of patients and a worsened rate of adherence in less than 10% of patients. PMID- 27653231 TI - Buzz off! An evaluation of ultrasonic acoustic vibration for the disruption of marine micro-organisms on sensor-housing materials. AB - : Biofouling is a process of ecological succession which begins with the attachment and colonization of micro-organisms to a submerged surface. For marine sensors and their housings, biofouling can be one of the principle limitations to long-term deployment and reliability. Conventional antibiofouling strategies using biocides can be hazardous to the environment, and therefore alternative chemical-free methods are preferred. In this study, custom-made testing assemblies were used to evaluate ultrasonic vibration as an antibiofouling process for marine sensor-housing materials over a 28-day time course. Microbial biofouling was measured based on (i) surface coverage, using fluorescence microscopy and (ii) bacterial 16S rDNA gene copies, using Quantitative polymerase chain reaction (PCR). Ultrasonic vibrations (20 KHz, 200 ms pulses at 2-s intervals; total power 16.08 W) significantly reduced the surface coverage on two plastics, poly(methyl methacrylate) and polyvinyl chloride (PVC) for up to 28 days. Bacterial gene copy number was similarly reduced, but the results were only statistically significant for PVC, which displayed the greatest overall resistance to biofouling, regardless of whether ultrasonic vibration was applied. Copper sheet, which has intrinsic biocidal properties was resistant to biofouling during the early stages of the experiment, but inhibited measurements made by PCR and generated inconsistent results later on. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, ultrasonic acoustic vibration is presented as a chemical free, ecologically friendly alternative to conventional methods for the perturbation of microbial attachment to submerged surfaces. The results indicate the potential of an ultrasonic antibiofouling method for the disruption of microbial biofilms on marine sensor housings, which is typically a principle limiting factor in their long-term operation in the oceans. With increasing deployment of scientific apparatus in aquatic environments, including further offshore and for longer duration, the identification and evaluation of novel antifouling strategies that do not employ hazardous chemicals are widely sought. PMID- 27653232 TI - AHNS series - Do you know your guidelines? Diagnosis and management of cutaneous squamous cell carcinoma. AB - This article is the next installment of the series "Do You Know Your Guidelines" presented by the Education Committee of the American Head and Neck Society. Guidelines for the prevention, diagnosis, workup, and management of cutaneous squamous cell carcinoma (SCC) are reviewed. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016. PMID- 27653234 TI - Weighing the risks and benefits of Pneumocystis pneumonia prophylaxis in iatrogenically immunosuppressed dermatology patients. PMID- 27653233 TI - Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling. AB - Photodynamic therapy (PDT) is known as a non-invasive treatment modality that is based on photochemical reactions between oxygen, photosensitizer, and a special wavelength of light. However, a dosimetric predictor for PDT outcome is still elusive because current dosimetric quantities do not account for the differences in the PDT oxygen consumption rate for different fluence rates. In this study, we evaluate several dose metrics, total fluence, photobleaching ratio, PDT dose, and mean reacted singlet oxygen (mean [1 O2 ]rx ) for predicting the PDT outcome and a clinically relevant tumor re-growth endpoint. For this reason, radiation induced fibrosarcoma (RIF) mice tumors are treated with 2-(1-Hexyloxyethyl)-2 devinyl pyropheophorbide (HPPH) and different in-air fluences (30 J/cm2 , 50 J/cm2 , 135 J/cm2 , 250 J/cm2 , and 350 J/cm2 ) and in-air fluence rates (20, 50, 75, 150 mW/cm2 ). Explicit measurements of HPPH and oxygen concentration as well as tissue optical properties are performed pre- and post-treatment. Then, this information is incorporated into a macroscopic model to calculate the photobleaching, PDT dose, and mean [1 O2 ]rx . Changes in tumor volume are tracked following the treatment and compared with the dose metrics. The correlation demonstrates that mean [1 O2 ]rx serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor re growth endpoint. PMID- 27653235 TI - Immunohistochemical markers for hepatocellular carcinoma prognosis after liver resection and liver transplantation. AB - AIM: There were differences in progression and prognosis of hepatocellular carcinoma (HCC) after surgery between liver resection (LR) and liver transplantation (LT). In this study, immunohistochemical (IHC) markers associated with the prognosis of HCC were assessed. METHODS: Data were collected from 167 patients who underwent LT (n=41) or LR (n=126) for HCC. IHC markers including alpha-fetoprotein (AFP), p53, Ki-67, cytokeratin 7 (CK7), and cytokeratin 19 (CK19) were compared between the treatment methods in tumor tissue. RESULTS: AFP- and p53-negative patients had a significantly higher survival rate than AFP- and p53-positive patients (AFP: disease-free survival [DFS] P=.006, overall survival [OS] P=.016; p53: DFS P=.005, OS P=.038) in the LR group. CK19 was related to DFS (P=.005), while CK7 (P=.014) and CK19 (P=.06) were related to OS in the LT group. When we combined factors that were significant in both groups (LR: AFP and p53, LT: CK7 and CK19), all-negative patients had a higher survival rate (LR: DFS P=.025, OS P=.043, LT: DFS P=.034, OS P=.008). CONCLUSION: p53 and AFP were predictors for poor prognosis of HCC after LR; CK7 and CK19 could be predictors for poor prognosis of patients with HCC after LT. PMID- 27653236 TI - Increasing the salience of fluency cues does not reduce the recognition memory impairment in Alzheimer's disease! AB - In Alzheimer's disease (AD), it is now well established that recollection is impaired from the beginning of the disease, whereas findings are less clear concerning familiarity. One of the most important mechanisms underlying familiarity is the sense of familiarity driven by processing fluency. In this study, we attempted to attenuate recognition memory deficits in AD by maximizing the salience of fluency cues in two conditions of a recognition memory task. In one condition, targets and foils have been created from the same pool of letters (Overlap condition). In a second condition, targets and foils have been derived from two separate pools of letters (No-Overlap condition), promoting the use of letter-driven visual and phonetic fluency. Targets and foils were low-frequency words. The memory tasks were performed by 15 patients with AD and 16 healthy controls. Both groups improved their memory performance in the No-Overlap condition compared to the Overlap condition. Patients with AD were able to use fluency cues during recognition memory as older adults did, but this did not allow to compensate for dysfunction of recognition memory processes. PMID- 27653237 TI - New perspectives on ACL injury: On the role of repetitive sub-maximal knee loading in causing ACL fatigue failure. AB - In this paper, we review a series of studies that we initiated to examine mechanisms of anterior cruciate ligament (ACL) injury in the hope that these injuries, and their sequelae, can be better prevented. First, using the earliest in vitro model of a simulated single-leg jump landing or pivot cut with realistic knee loading rates and trans-knee muscle forces, we identified the worst-case dynamic knee loading that causes the greatest peak ACL strain: Combined knee compression, flexion, and internal tibial rotation. We also identified morphologic factors that help explain individual susceptibility to ACL injury. Second, using the above knee loading, we introduced a possible paradigm shift in ACL research by demonstrating that the human ACL can fail by a sudden rupture in response to repeated sub-maximal knee loading. If that load is repeated often enough over a short time interval, the failure tended to occur proximally, as observed clinically. Third, we emphasize the value of a physical exam of the hip by demonstrating how limited internal axial rotation at the hip both increases the susceptibility to ACL injury in professional athletes, and also increases peak ACL strain during simulated pivot landings, thereby further increasing the risk of ACL fatigue failure. When training at-risk athletes, particularly females with their smaller ACL cross-sections, rationing the number and intensity of worst-case knee loading cycles, such that ligament degradation is within the ACL's ability to remodel, should decrease the risk for ACL rupture due to ligament fatigue failure.(c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2059-2068, 2016. PMID- 27653239 TI - Rosuvastatin limits the activation of hepatic stellate cells in diet-induced obese mice. AB - AIM: The aim of this study was to investigate the effects of rosuvastatin in a model of diet-induced obesity and non-alcoholic fatty liver disease, with attention to the activation of hepatic stellate cells (HSCs). METHOD: Male C57BL/6 mice received a control diet (C; 10% energy as lipids) or a high-fat diet (HF; 50% energy as lipids) for 12 weeks, followed by 7 weeks of treatment. Group CR received control diet + rosuvastatin; group HFR received high-fat diet + rosuvastatin. RESULTS: The HF group showed higher insulin, total cholesterol, triacylglycerol, and leptin levels than the C group, all of which were significantly diminished by rosuvastatin in the HFR group. The HF group had greater steatosis and activated HSCs than the C group, whereas rosuvastatin diminished the steatosis (less 21%, P < 0.001) and significantly inhibited the activation of the HSCs in the HFR group compared to the HF group. The sterol regulatory element-binding protein-1 and the peroxisome proliferator-activated receptor (PPAR)-gamma protein expressions were increased in HF animals and reduced after treatment in the HFR group. By contrast, low PPAR-alpha and carnitine palmitoyltransferase-1 expressions were found in the HF group, and were restored by rosuvastatin treatment in the HFR group. CONCLUSION: Rosuvastatin mitigated hepatic steatosis by modulating PPAR balance, favoring PPAR-alpha over PPAR-gamma downstream effects. The effects were accompanied by a diminishing of insulin resistance, the anti-inflammatory adipokine profile, and HSC activation, avoiding non-alcoholic fatty liver disease progression and non-alcoholic steatohepatitis onset in this model. PMID- 27653238 TI - Applied Concepts in PBPK Modeling: How to Build a PBPK/PD Model. AB - The aim of this tutorial is to introduce the fundamental concepts of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling with a special focus on their practical implementation in a typical PBPK model building workflow. To illustrate basic steps in PBPK model building, a PBPK model for ciprofloxacin will be constructed and coupled to a pharmacodynamic model to simulate the antibacterial activity of ciprofloxacin treatment. PMID- 27653240 TI - Bone Density Loss Is Associated With Blood Cell Counts. AB - Hematopoiesis depends on a supportive microenvironment. Preclinical studies in mice have demonstrated that osteoblasts influence the development of blood cells, particularly erythrocytes, B lymphocytes, and neutrophils. However, it is unknown whether osteoblast numbers or function impact blood cell counts in humans. We tested the hypothesis that men with low BMD or greater BMD loss have decreased circulating erythrocytes and lymphocytes and increased myeloid cells. We performed a cross-sectional analysis and prospective analysis in the Osteoporotic Fractures in Men (MrOS) study, a multisite longitudinal cohort study. A total of 2571 community-dwelling men (>=65 years) who were able to walk without assistance, did not have a hip replacement or fracture, and had complete blood counts (CBCs) at the third study visit were analyzed. Multivariable (MV)-adjusted logistic regression estimated odds of white blood cell (WBC) subtypes (highest and lowest quintile versus middle), and anemia (clinically defined) associated with BMD by DXA scan (at visit 3), annualized percent BMD change (baseline to visit 3), and high BMD loss (>0.5%/year, from baseline to visit 3) at the femoral neck (FN) and total hip (TH). MV-adjusted models included age, BMI, cancer history, smoking status, alcohol intake, corticosteroid use, self-reported health, thiazide use, and physical activity. At visit 3 greater TH BMD loss (per 1 SD) was associated with increased odds of anemia, high neutrophils, and low lymphocytes. Annualized BMD loss of >0.5% was associated with increased odds of anemia, high neutrophils, and low lymphocytes. Similar results were observed for FN BMD regarding anemia and lymphocytes. We conclude that community-dwelling older men with declining hip BMD over about 7 years had increased risks of anemia, lower lymphocyte count, and higher neutrophil count, consistent with preclinical studies. Bone health and hematopoiesis may have greater interdependency than previously recognized. (c) 2016 American Society for Bone and Mineral Research. PMID- 27653241 TI - Endothelial-smooth muscle cell interactions in the regulation of vascular tone in skeletal muscle. AB - The SMCs of skeletal muscle arterioles are intricately sensitive to changes in membrane potential. Upon increasing luminal pressure, the SMCs depolarize, thereby opening VDCCs, which leads to contraction. Mechanisms that oppose this myogenic tone can involve voltage-dependent and independent dilator pathways, and can be endothelium-dependent or independent. Of particular interest are the pathways leading to hyperpolarization of SMCs, as these can potentially evoke both local and conducted dilation. This review focuses on three agonists that cause local and conducted dilation in skeletal muscle: ACh, ATP, and KCl. The mechanisms for the release of these agonists during motor nerve stimulation and/or hypoxia, and their actions to open either Ca2+ -activated K+ channels (KCa ) or inwardly rectifying K+ channels (KIR ) are described. By causing local and conducted dilation, each agonist has the ability to improve skeletal muscle blood flow during exercise and ischemia. PMID- 27653244 TI - Capillary Displacement of Viscous Liquids in Geometries with Axial Variations. AB - Axial variations in geometry and presence of viscous displaced fluid are known to alter the diffusive-dynamics of capillary imbibition of a wetting liquid. We here show that the coupled effect of axially varying capillary geometry and finite viscosity of the displaced fluid can lead to significant variations in both short and long time dynamics of imbibition. Based on a theoretical model and lattice Boltzmann simulations, we analyze capillary displacement of a viscous liquid in straight and diverging capillaries. At short times, the imbibition length scales proportionally with time as opposed to the diffusive-dynamics of imbibition of a single wetting liquid. Whereas, at long times, geometry-dependent power-law behavior occurs which qualitatively resembles single liquid imbibition. The distance at which the crossover between these two regimes occurs depends strongly on the viscosities of the imbibing and the displaced liquid. Additionally, our simulations show that the early time imbibition dynamics are also affected by the dynamic contact angle of the meniscus. PMID- 27653243 TI - Effect of Hydroxymethylcytosine on the Structure and Stability of Holliday Junctions. AB - 5-Hydroxymethylcytosine (5hmC) is an epigenetic marker that has recently been shown to promote homologous recombination (HR). In this study, we determine the effects of 5hmC on the structure, thermodynamics, and conformational dynamics of the Holliday junction (the four-stranded DNA intermediate associated with HR) in its native stacked-X form. The hydroxymethyl and the control methyl substituents are placed in the context of an amphimorphic GxCC trinucleotide core sequence (where xC is C, 5hmC, or the methylated 5mC), which is part of a sequence also recognized by endonuclease G to promote HR. The hydroxymethyl group of the 5hmC junction adopts two distinct rotational conformations, with an in-base-plane form being dominant over the competing out-of-plane rotamer that has typically been seen in duplex structures. The in-plane rotamer is seen to be stabilized by a more stable intramolecular hydrogen bond to the junction backbone. Stabilizing hydrogen bonds (H-bonds) formed by the hydroxyl substituent in 5hmC or from a bridging water in the 5mC structure provide approximately 1.5-2 kcal/mol per interaction of stability to the junction, which is mostly offset by entropy compensation, thereby leaving the overall stability of the G5hmCC and G5mCC constructs similar to that of the GCC core. Thus, both methyl and hydroxymethyl modifications are accommodated without disrupting the structure or stability of the Holliday junction. Both 5hmC and 5mC are shown to open the structure to make the junction core more accessible. The overall consequences of incorporating 5hmC into a DNA junction are thus discussed in the context of the specificity in protein recognition of the hydroxymethyl substituent through direct and indirect readout mechanisms. PMID- 27653245 TI - The accuracy of the SenseWear Pro3 and the activPAL3 Micro devices for measurement of energy expenditure. AB - Activity monitors such as the SenseWear Pro3 (SWP3) and the activPAL3 Micro (aP3M) are regularly used by researchers and practitioners to provide estimates of the metabolic cost (METs) of activities in free-living settings. The purpose of this study is to examine the accuracy of the MET predictions from the SWP3 and the aP3M compared to the criterion standard MET values from indirect calorimetry. Fifty-six participants (mean age: 39.9 (+/-11.5), 25M/31F) performed eight activities (four daily living, three ambulatory and one cycling), while simultaneously wearing a SWP3, aP3M and the Cosmed K4B2 (K4B2) mobile metabolic unit. Paired samples T-tests were used to examine differences between device predicted METs and criterion METs. Bland-Altman plots were constructed to examine the mean bias and limits of agreement for predicted METs compared to criterion METs. SWP3 predicted MET values were significantly different from the K4B2 for each activity (p ? 0.004), excluding sweeping (p = 0.122). aP3M predicted MET values were significantly different (p < 0.001) from the K4B2 for each activity. When examining the activities collectively, both devices underestimated activity intensity (0.20 METs (SWP3), 0.95 METs (aP3M)). The greatest mean bias for the SWP3 was for cycling (-3.25 METs), with jogging (-5.16 METs) producing the greatest mean bias for the aP3M. All of the activities (excluding SWP3 sweeping) were significantly different from the criterion measure. Although the SWP3 predicted METs are more accurate than their aP3M equivalent, the predicted MET values from both devices are significantly different from the criterion measure for the majority of activities. PMID- 27653246 TI - Genome-wide identification and expression analysis of the apple ASR gene family in response to Alternaria alternata f. sp. mali. AB - The ABA/water stress/ripening-induced (ASR) gene family exists universally in higher plants, and many ASR genes are up-regulated during periods of environmental stress and fruit ripening. Although a considerable amount of research has been performed investigating ASR gene response to abiotic stresses, relatively little is known about their roles in response to biotic stresses. In this report, we identified five ASR genes in apple (Malus * domestica) and explored their phylogenetic relationship, duplication events, and selective pressure. Five apple ASR genes (Md-ASR) were divided into two clades based on phylogenetic analysis. Species-specific duplication was detected in M. domestica ASR genes. Leaves of 'Golden delicious' and 'Starking' were infected with Alternaria alternata f. sp. mali, which causes apple blotch disease, and examined for the expression of the ASR genes in lesion areas during the first 72 h after inoculation. Md-ASR genes showed different expression patterns at different sampling times in 'Golden delicious' and 'Starking'. The activities of stress related enzymes, peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), phenylalanine ammonia lyase (PAL), and polyphenoloxidase (PPO), and the content of malondialdehyde (MDA) were also measured in different stages of disease development in two cultivars. The ASR gene expression patterns and theses physiological indexes for disease resistance suggested that Md-ASR genes are involved in biotic stress responses in apple. PMID- 27653247 TI - A shot in the arm for front line staff. AB - Emergency department matron Amanda Webb was among the first front line staff at University College Hospital, London, to receive the swine flu vaccine as part of a mass immunisation programme launched last month. PMID- 27653248 TI - Introduction of CCTV expected to reduce violence against staff. AB - Closed circuit television cameras are to be introduced into emergency departments across Wales to protect nurses against violent attacks. PMID- 27653242 TI - Prevalence of personal weight control attempts in adults: a systematic review and meta-analysis. AB - The purpose of this systematic review and meta-analysis was to estimate the prevalence of personal weight control attempts (weight loss and/or maintenance) worldwide and to identify correlates, personal strategies used and the underlying motives. We included epidemiological/observational studies of adults (>=18 years) reporting prevalence of weight control attempts in the past-year. Seventy-two studies (n = 1,184,942) met eligibility criteria. Results from high quality studies showed that 42% of adults from general populations and 44% of adults from ethnic-minority populations reported trying to lose weight, and 23% of adults from general populations reported trying to maintain weight annually. In general population studies, higher prevalence of weight loss attempts was observed in the decade of 2000-2009 (48.2%), in Europe/Central Asia (61.3%) and in overweight/obese individuals and in women (p < 0.01). Of the 37 strategies (grouped in 10 domains of the Oxford Food and Activity Behaviours Taxonomy) and 12 motives reported for trying to control weight, exercising and dieting (within the energy compensation and restraint domains, respectively) and wellbeing and long-term health were the most prevalent. To our knowledge, this is the first systematic review to investigate weight control attempts worldwide. Key strategies and motives were identified which have implications for future public health initiatives on weight control. PMID- 27653251 TI - Board's eye view. AB - Many of us who work in emergency care ensure daily that the four-hour operational standard is met. And, as more patients are admitted over the coming winter, meeting this challenge will become harder. PMID- 27653250 TI - Urgent care patients with alcohol problems to receive 'binge packs'. AB - Turning point, a leading UK social care organisation, is distributing 'binge packs' to emergency departments (EDs) to tackle increasing levels of alcohol misuse among members of the public. PMID- 27653252 TI - Diary. AB - Our roundup of what's on. PMID- 27653254 TI - Wound care. AB - Wounds UK, at www.wounds-uk.com is a site devoted to the promotion of good practice in wound care and the provision of affordable and accessible educational resources. PMID- 27653253 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27653255 TI - Patient experience. AB - The Division of Public Health and Primary Health Care, at the University of Oxford, runs an award-winning website, at www.healthtalkonline.org , concerning people's experiences of health and illness. PMID- 27653256 TI - Web scan. AB - Do you know how to use dressings correctly so that you do not waste money by making them ineffective? Many staff are unfamiliar with the properties of the dressings they use regularly but it is possible to obtain all the important information from www.dressings.org. PMID- 27653257 TI - New developments in work-related asthma. AB - INTRODUCTION: Work-related asthma includes two subtypes: occupational asthma or asthma caused by specific agents (sensitizers or irritants) in the workplace, and work-exacerbated asthma or pre-existing asthma worsened by workplace exposures. Areas covered: This review provides an update on the definitions and the clinical features of the different work-related asthma subtypes as well as new insights into their etiology and the pathophysiological mechanisms involved. The diagnosis of work-related asthma should be made on objective basis using a constellation of clinical, physiologic and allergologic tests. Specific inhalation challenge with the suspected occupational agent(s) remains as the reference standard for diagnosis. A literature search was performed using the following terms: work related asthma, occupational asthma, work-exacerbated asthma, irritant-induced asthma and etiological agents. Expert commentary: Studies focusing on the biological effects and mechanisms of environmental exposures in the development of sensitizer-induced or irritant-induced asthma in various workplace settings are of greatest interest. An integrative approach that combines clinical parameters with component-resolved diagnosis as well as inflammatory biomarkers appears to be very promising. Occupational allergy provides a good opportunity to understand the complex relationships between exposure to allergens in the workplace, interaction with genes and the co-exposures to other factors in the working environment. PMID- 27653258 TI - Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2 FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1 relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology. PMID- 27653259 TI - Science and impact: the challenge faced by Dental Press Journal of Orthodontics. PMID- 27653260 TI - Miniscrew-assisted rapid palatal expander (MARPE): the quest for pure orthopedic movement. AB - The midpalatal suture has bone margins with thick connective tissue interposed between them, and it does not represent the fusion of maxillary palatal processes only, but also the fusion of palatal processes of the jaws and horizontal osseous laminae of palatal bones. Changing it implies affecting neighboring areas. It has got three segments that should be considered by all clinical analyses, whether therapeutic or experimental: the anterior segment (before the incisive foramen, or intermaxillary segment), the middle segment (from the incisive foramen to the suture transversal to the palatal bone ) and the posterior segment (after the suture transversal to the palatal bone ). Rapid palatal expansion might be recommended for patients at the final pubertal growth stage, in addition to adult patients with maxillary constriction. It represents a treatment solution that can potentially avoid surgical intervention. When performed in association with rapid palatal expanders, it might enhance the skeletal effects of the latter. Of the various designs of expansion appliances, MARPE (miniscrew-assisted rapid palatal expander) has been modified in order to allow its operational advantages and outcomes to become familiar in the clinical practice. PMID- 27653261 TI - An interview with Kotaro Tanimoto. PMID- 27653262 TI - Influence of ligation method on friction resistance of lingual brackets with different second-order angulations: an in vitro study. AB - OBJECTIVE: To evaluate stainless steel archwire static friction in active and passive self-ligating lingual and conventional brackets with second-order angulations. METHODS: Two conventional lingual brackets for canines (STb light/Ormco; PSWb/Tecnident), and two self-ligating brackets, one active (In Ovation L/GAC) and the other passive (3D/ Forestadent), were evaluated. A stainless steel archwire was used at 0 degrees , 3 degrees and 5 degrees angulations. Metal ligatures, conventional elastic ligatures, and low friction elastic ligatures were also tested. A universal testing machine applied friction between brackets and wires, simulating sliding mechanics, to produce 2-mm sliding at 3 mm/minute speed. RESULTS: Two-way analysis of variance demonstrated a significant effect of the interaction between brackets and angulations (p < 0.001). Tukey test indicated that the highest frictional resistance values were observed at 5 degrees angulation for In-Ovation L, PSWb bracket with non conventional ligature, and STb bracket with metal ligature. As for 3D, PSWb with conventional or metal ligatures, and STb brackets with non conventional ligature, showed significantly lower static frictional resistance with 0 degrees angulation. At 0 degrees angulation, STb brackets with metal ties, In-Ovation L brackets and 3D brackets had the lowest frictional resistance. CONCLUSIONS: As the angulation increased from 0 degrees to 3 degrees , static friction resistance increased. When angulation increased from 3 degrees to 5 degrees , static friction resistance increased or remained the same. Self-ligating 3D and In-Ovation L brackets, as well as conventional STb brackets, seem to be the best option when sliding mechanics is used to perform lingual orthodontic treatment. PMID- 27653263 TI - Diagnostic performance of various cephalometric parameters for the assessment of vertical growth pattern. AB - INTRODUCTION: Multiple cephalometric analyses are used to diagnose vertical skeletal facial discrepancy. A multitude of times, these parameters show conflicting results, and a specific diagnosis is hard to reach. OBJECTIVE: Hence, this study aimed to identify the skeletal analysis that performs best for the identification of vertical skeletal pattern in borderline cases. METHODS: The sample consisted of 161 subjects (71 males and 90 females; mean age = 23.6 +/- 4.6 years). Y-axis, Sella-Nasion to mandibular plane angle (SN.MP), maxillary plane to mandibular plane angle (MMA), Sella-Nasion to Gonion-Gnathion angle (SN.GoGn), Frankfort to mandibular plane angle (FMA), R-angle and facial height ratio (LAFH.TAFH) were used to evaluate vertical growth pattern on lateral cephalograms. The subjects were divided into three groups (hypodivergent, normodivergent and hyperdivergent groups), as indicated by the diagnostic results of the majority of parameters. Kappa statistics was applied to compare the diagnostic accuracy of various analyses. To further validate the results, sensitivity and positive predictive values (PPV) for each parameter were also calculated. RESULTS: SN.GoGn showed a substantial interclass agreement (k = 0.850). In the hypodivergent group, MMA showed the highest sensitivity (0.934), whereas FMA showed the highest PPV (0.964). In the normodivergent group, FMA showed the highest sensitivity (0.909) and SN.GoGn had the highest PPV (0.903). SN.GoGn showed the highest sensitivity (0.980) and PPV (0.87) in the hyperdivergent group. CONCLUSIONS: SN.GoGn and FMA were found to be the most reliable indicators, whereas LAFH.TAFH is the least reliable indicator in assessing facial vertical growth pattern. Hence, the cephalometric analyses may be limited to fewer analyses of higher diagnostic performance. PMID- 27653264 TI - Comparative evaluation of soft tissue changes in Class I borderline patients treated with extraction and nonextraction modalities. AB - OBJECTIVE: To compare soft tissue changes in Class I borderline cases treated with extraction and nonextraction modalities. METHODS: A parent sample of 150 patients with Class I dental and skeletal malocclusion (89 patients treated with premolar extraction and 61 patients without extraction) was randomly selected and subjected to discriminant analysis which identified the borderline sample of 44 patients (22 extraction and 22 nonextraction patients). Pretreatment and post treatment cephalograms of the borderline subsample were analyzed using 22 soft tissue parameters. RESULTS: Upper and lower lips were more retracted and thickness of the upper lip increased more in the borderline extraction cases (p < 0.01). The nasolabial angle became more obtuse and the interlabial gap was reduced in the borderline extraction cases (p < 0.01). Lower lip, interlabial gap and nasolabial angle showed no changes in the borderline nonextraction cases. CONCLUSION: The soft tissue parameters which can be used as guideline in decision making to choose either extraction or nonextraction in Class I borderline cases are upper and lower lip protrusion in relation to the E-plane and Sn-Pg' line, lower lip protrusion in relation to the true vertical line (TVL), upper lip thickness, nasolabial angle and interlabial gap. PMID- 27653265 TI - Cleansing orthodontic brackets with air-powder polishing: effects on frictional force and degree of debris. AB - INTRODUCTION: Debris buildup on the bracket-wire interface can influence friction. Cleansing brackets with air-powder polishing can affect this process. OBJECTIVE: The aim of this study was to evaluate the frictional force and amount of debris remaining on orthodontic brackets subjected to prophylaxis with air powder polishing. METHODS: Frictional force and debris buildup on the surface of 28 premolar brackets were evaluated after orthodontic treatment. In one hemiarch, each bracket was subjected to air-powder polishing (n = 14) for five seconds, while the contralateral hemiarch (n = 14) served as control. Mechanical friction tests were performed and images of the polished bracket surfaces and control surfaces were examined. Wilcoxon test was applied for comparative analysis between hemiarches at p < 0.05. RESULTS: Brackets that had been cleaned with air powder polishing showed lower friction (median = 1.27 N) when compared to the control surfaces (median = 4.52 N) (p < 0.01). Image analysis showed that the control group exhibited greater debris buildup (median = 2.0) compared with the group that received prophylaxis with air-powder polishing (median = 0.5) (p < 0.05). CONCLUSION: Cleansing orthodontic brackets with air-powder polishing significantly reduces debris buildup on the bracket surface while decreasing friction levels observed during sliding mechanics. PMID- 27653266 TI - Digital orthodontic radiographic set versus cone-beam computed tomography: an evaluation of the effective dose. AB - OBJECTIVE: The aim of this study was to compare the equivalent and effective doses of different digital radiographic methods (panoramic, lateral cephalometric and periapical) with cone-beam computed tomography (CBCT). METHODS: Precalibrated thermoluminescent dosimeters were placed at 24 locations in an anthropomorphic phantom (Alderson Rando Phantom, Alderson Research Laboratories, New York, NY, USA), representing a medium sized adult. The following devices were tested: Heliodent Plus (Sirona Dental Systems, Bernsheim, Germany), Orthophos XG 5 (Sirona Dental Systems, Bernsheim, Germany) and i-CAT (Imaging Sciences International, Hatfield, PA, USA). The equivalent doses and effective doses were calculated considering the recommendations of the International Commission of Radiological Protection (ICRP) issued in 1990 and 2007. RESULTS: Although the effective dose of the radiographic set corresponded to 17.5% (ICRP 1990) and 47.2% (ICRP 2007) of the CBCT dose, the equivalent doses of skin, bone surface and muscle obtained by the radiographic set were higher when compared to CBCT. However, in some areas, the radiation produced by the orthodontic set was higher due to the complete periapical examination. CONCLUSION: Considering the optimization principle of radiation protection, i-CAT tomography should be used only in specific and justified circumstances. Additionally, following the ALARA principle, single periapical radiographies covering restricted areas are more suitable than the complete periapical examination. PMID- 27653267 TI - Is there an association between skeletal asymmetry and tooth absence? AB - INTRODUCTION: Facial skeletal asymmetry is commonly found in humans and its main characteristic is menton deviation. The literature suggests that occlusal and masticatory problems arising from tooth absence could be related to the development of such asymmetries. OBJECTIVE: The aim of this cross-sectional study was to estimate the prevalence of mandibular skeletal asymmetries and to investigate its association with posterior tooth absences. METHODS: Tomographic images of 952 individuals aged from 18 to 75 years old were used. Asymmetry was the analyzed outcome, and it was categorized into three groups according to gnathion displacement in relation to the midsagittal plane (relative symmetry, moderate asymmetry, and severe asymmetry). Patients were sorted by the presence of all posterior teeth, unilateral posterior tooth absence, or bilateral posterior tooth absence. Chi-square test with a significance level of 5% was used to verify the association between posterior tooth absence and asymmetry. RESULTS: Results show relative symmetry present in 55.3% of the sample, as well as the prevalence of 27.3% for moderate mandibular asymmetry and 17.4% for severe asymmetry. Moderate and severe mandibular asymmetries occurred in a higher proportion in patients with unilateral posterior tooth absence. However, there was no statistically significant difference between the analyzed groups (p = 0.691). CONCLUSIONS: In this study, mandibular asymmetries did not present any association with the absence of teeth on the posterior area of the arch. PMID- 27653268 TI - A comparison between two lingual orthodontic brackets in terms of speech performance and patients' acceptance in correcting Class II, Division 1 malocclusion: a randomized controlled trial. AB - OBJECTIVE: To compare speech performance and levels of oral impairment between two types of lingual brackets. METHODS: A parallel-group randomized controlled trial was carried out on patients with Class II, Division 1 malocclusion treated at the University of Hama School of Dentistry in Hama, Syria. A total of 46 participants (mean age: 22.3 +/- 2.3 years) with maxillary dentoalveolar protrusion were randomly distributed into two groups with 23 patients each (1:1 allocation ratio). Either STb (Ormco) or 7th Generation (Ormco) lingual brackets were applied. Fricative sound/s/ spectrograms were analyzed directly before intervention (T0), one week following premolar extraction prior to bracket placement (T1), within 24 hours of bracket bonding (T2), one month after (T3), and three months after (T4) bracket placement. Patients' acceptance was assessed by means of standardized questionnaires. RESULTS: After bracket placement, significant deterioration in articulation was recorded at all assessment times in the 7th Generation group, and up to T3 in the STb group. Significant intergroup differences were detected at T2 and T3. No statistically significant differences were found between the two groups in reported tongue irritation levels, whereas chewing difficulty was significantly higher in the 7th Generation group one month after bracket placement. CONCLUSIONS: 7th Generation brackets have more interaction with sound production than STb ones. Although patients in both groups complained of some degree of oral impairment, STb appliances appeared to be more comfortable than the 7th Generation ones, particularly within the first month of treatment. PMID- 27653269 TI - Orthodontic camouflage of skeletal Class III malocclusion with miniplate: a case report. AB - INTRODUCTION: Skeletal Class III malocclusion is often referred for orthodontic treatment combined with orthognathic surgery. However, with the aid of miniplates, some moderate discrepancies become feasible to be treated without surgery. OBJECTIVE: To report the case of a 24-year-old man with severe skeletal Angle Class III malocclusion with anterior crossbite and a consequent concave facial profile. METHODS: The patient refused to undergo orthognathic surgery; therefore, orthodontic camouflage treatment with the aid of miniplates placed on the mandibular arch was proposed. RESULTS: After 18 months of treatment, a Class I molar and canine relationship was achieved, while anterior crossbite was corrected by retraction of mandibular teeth. The consequent decrease in lower lip fullness and increased exposure of maxillary incisors at smiling resulted in a remarkable improvement of patient's facial profile, in addition to an esthetically pleasing smile, respectively. One year later, follow-up revealed good stability of results. PMID- 27653270 TI - Class II malocclusion associated with mandibular deficiency and maxillary and mandibular crowding: follow-up evaluation eight years after treatment completion. AB - This report describes the correction of a clinical case of malocclusion with anteroposterior discrepancy and transverse, sagittal and vertical deficiencies. A nonextraction technique was used to preserve space in the dental arches and control facial growth for the correction of the sagittal skeletal relationship and of overbite. The mechanics adopted efficiently corrected malocclusion: all functional and esthetic goals were achieved, and results remained stable eight years after treatment completion. This case was presented to the Committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO) as part of the requirements necessary to obtain the BBO Diploma. PMID- 27653271 TI - Functional Aesthetic Occlusal Plane (FAOP). AB - INTRODUCTION: A reasonable exposure of incisors and gingival tissues is generally considered more attractive than excess or lack of exposure. A reasonable gingival exposure is considered to be around 0 to 2 mm when smiling and 2-4 mm exposure of the maxillary incisor edge when the lips are at rest. OBJECTIVE: The aim of this paper is to present the Functional Aesthetic Occlusal Plane (FAOP), which aims to help in the diagnosis of the relationships established among molars, incisors and the upper lip. CONCLUSION: FAOP can complement an existing and established orthodontic treatment plan, facilitating the visualization of functional and aesthetic demands by giving a greater focus on the position of incisors in the relationship established among the incisors, molars and the upper lip stomion. PMID- 27653272 TI - Structural basis for the phosphorylation of FUNDC1 LIR as a molecular switch of mitophagy. AB - Mitophagy is a fundamental process that determines mitochondrial quality and homeostasis. Several mitophagy receptors, including the newly identified FUNDC1, mediate selective removal of damaged or superfluous mitochondria through their specific interaction with LC3. However, the precise mechanism by which this interaction is regulated to initiate mitophagy is not understood. Here, we report the solution structure of LC3 in complex with a peptide containing the FUNDC1 LC3 interacting region (LIR) motif. The structure reveals a noncanonical LC3-LIR binding conformation, in which the third LIR residue (Val20) is also inserted into the hydrophobic pocket of LC3, together with the conserved residues Tyr18 and Leu21. This enables Tyr18 to be positioned near Asp19 of LC3, and thus phosphorylation of Tyr18 significantly weakens the binding affinity due to electrostatic repulsion. Functional analysis revealed that mitochondrial targeting of the LIR-containing cytosolic portion of FUNDC1 is necessary and sufficient to initiate mitophagy when Tyr18 is unphosphorylated, even in the absence of mitochondrial fragmentation. Thus, we demonstrated that phosphorylation of Tyr18 of FUNDC1 serves as a molecular switch for mitophagy. This may represent a novel target for therapeutic intervention. PMID- 27653274 TI - Fluorescence-based assay as a new screening tool for toxic chemicals. AB - Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID- 27653275 TI - Corrigendum: Paired arrangement of kinetochores together with microtubule pivoting and dynamics drive kinetochore capture in meiosis I. PMID- 27653273 TI - Non-professional marathon running: RAGE axis and ST2 family changes in relation to open-window effect, inflammation and renal function. AB - Conflicting data exist on the relevance of marathon (M) and half marathon (HM) running for health. The number of non-professional athletes finishing M and HM events is steadily growing. In order to investigate molecular changes occurring in amateur athletes, we enrolled 70 non-professional runners finishing a single M (34) or HM (36) event at baseline, the finish line and during recovery, and 30 controls. The measurement of the Receptor for Advanced Glycation Endproducts, Interleukin 1 receptor antagonist, ST2 and cytokeratin 18 was combined with molecules measured during clinical routine. Results were analyzed in the light of blood cell analysis, lactate measurements, correction for changes in plasma volume and body composition assessments. There were intrinsic differences in body mass index, abdominal body fat percentage and training time between M and HM runners. C-reactive protein changes in M and HM runners. While soluble RAGE, AGEs and ST2 increased immediately after the race in HM runners, HMGB1 increased in HM and M after the race and declined to baseline after a recovery period. We give insights into the regulation of various molecules involved in physical stress reactions and their possible implications for the cardiovascular system or renal function. PMID- 27653276 TI - Recognition for peer review. PMID- 27653277 TI - Interaction between 8-methoxypsoralen and trypsin: Monitoring by spectroscopic, chemometrics and molecular docking approaches. AB - 8-Methoxypsoralen (8-MOP) is a naturally occurring furanocoumarin with various biological activities. However, there is little information on the binding mechanism of 8-MOP with trypsin. Here, the interaction between 8-MOP and trypsin in vitro was determined by multi-spectroscopic methods combined with the multivariate curve resolution-alternating least squares (MCR-ALS) chemometrics approach. An expanded UV-vis spectral data matrix was analysed by MCR-ALS, the concentration profiles and pure spectra for the three reaction species (trypsin, 8-MOP and 8-MOP-trypsin) were obtained to monitor the interaction between 8-MOP and trypsin. The fluorescence data suggested that a static type of quenching mechanism occurred in the binding of 8-MOP to trypsin. Hydrophobic interaction dominated the formation of the 8-MOP-trypsin complex on account of the positive enthalpy and entropy changes, and trypsin had one high affinity binding site for 8-MOP with a binding constant of 3.81*104Lmol-1 at 298K. Analysis of three dimensional fluorescence, UV-vis absorption and circular dichroism spectra indicated that the addition of 8-MOP induced the rearrangement of the polypeptides carbonyl hydrogen-bonding network and the conformational changes in trypsin. The molecular docking predicted that 8-MOP interacted with the catalytic residues His57, Asp102 and Ser195 in trypsin. The binding patterns and trypsin conformational changes may result in the inhibition of trypsin activity. This study has provided insights into the binding mechanism of 8-MOP with trypsin. PMID- 27653278 TI - Representational changes of latent strategies in rat medial prefrontal cortex precede changes in behaviour. AB - The ability to change behavioural strategies in the face of a changing world has been linked to the integrity of medial prefrontal cortex (mPFC) function in several species. While recording studies have found that mPFC representations reflect the strategy being used, lesion studies suggest that mPFC is necessary for changing strategy. Here we examine the relationship between representational changes in mPFC and behavioural strategy changes in the rat. We found that on tasks with a forced change in reward criterion, strategy-related representational transitions in mPFC occurred after animals learned that the reward contingency had changed, but before their behaviour changed. On tasks in which animals made their own strategic decisions, representational transitions in mPFC preceded changes in behaviour. These results suggest that mPFC does not merely reflect the action-selection policy of the animal, but rather that mPFC processes information related to a need for a change in strategy. PMID- 27653279 TI - Differential proteomic analysis of platelets suggested target-related proteins in rabbit platelets treated with Rhizoma Corydalis. AB - CONTEXT: Corydalis yanhusuo W.T. Wang (Papaveraceae) (Rhizoma Corydalis) showed inhibitory effects on rabbit platelet aggregation induced by ADP, thrombin (THR) or arachidonic acid (AA). OBJECTIVE: This study separates and identifies the possible target-related platelet proteins and suggests possible signal cascades of RC antiplatelet aggregation. MATERIALS AND METHODS: Based on comparative proteomics, the differentially expressed platelet proteins treated before and after with 50 mg/mL RC 90% ethanol extract (for 15 min at 37 degrees C) were analyzed and identified by two dimensional gel electrophoresis (2-DE) and MALDI TOF-MS/MS. To further verify the possible signalling pathways of RC antiplatelet aggregation function, the concentration of calcium (Ca2+) was measured by Fura 2/AM fluorescence (Ex 340/380 nm, Em 500 nm) (RC final concentrations of 0.0156 0.1563 mg/mL), the levels of P-selectin and cyclic guanosine monophosphate (cGMP) were quantified by ELISA (OD. 450 nm) (RC final concentrations of 0.0156-1.5625 mg/mL), and the 5-hydroxytryptamine (5-HT) level was measured using ortho phthalaldehyde (OPT) fluorescence (Ex 340 nm, Em 470 nm) (RC final concentrations of 0.3125-1.5625 mg/mL). RESULTS: The expression of 52 proteins were altered in rabbit platelets after the treatment and the MALDI-TOF-MS analysis indicated that those proteins include 12 cytoskeleton proteins, 7 cell signalling proteins, 3 molecular chaperone proteins, 6 proteins related to platelet function, 16 enzymes and 7 other related proteins. Furthermore, RC extract could decrease the levels of 5-HT [inhibition rate of 96.80% (p < 0.05, vs. THR-activated group) treated with 0.7813 mg/mL of RC], Ca2+ [172.73 +/- 5.07 to 113.56 +/- 5.46 nM (p < 0.001, vs. THR-activated group) treated with 0.0313 mg/mL of RC] and P-selectin [13.48 +/- 0.96 ng/3 * 108 to 11.64 +/- 0.17 ng/3 * 108 (p < 0.05, vs. THR-activated group) treated with 0.0156 mg/mL of RC], and increase in cGMP level [38.93 +/- 0.57 to 50.26 +/- 4.05 ng/3 * 108 (p < 0.05, vs. THR-activated group) treated with 1.5165 mg/mL of RC] in ADP (10 MUmol/L), THR (0.25 u/mL) or AA-(0.205 mmol/L) activated rabbit platelets. DISCUSSION AND CONCLUSION: The present study indicated that P2Y12 receptor might be one of the direct target proteins of RC in platelets. The signal cascades network of RC after binding with P2Y12 receptor is mediating Galphai proteins to activate downstream signalling pathways (AC and/or PI3K signalling pathways) for the inhibition of platelet aggregation. PMID- 27653280 TI - The impact of adding assistants in nursing to acute care hospital ward nurse staffing on adverse patient outcomes: An analysis of administrative health data. AB - OBJECTIVES: The aim of this study was to assess the impact of adding assistants in nursing to acute care hospital ward nurse staffing on adverse patient outcomes using administrative health data. DESIGN: Logistic regression modelling was used with linked administrative health data to examine the association between seven adverse patient outcomes and use of assistants in nursing utilising a pre test/post-test design. Outcomes included were in-hospital 30-day mortality, failure to rescue, urinary tract infection, pressure injury, pneumonia, sepsis and falls with injury. SETTING: Eleven acute care metropolitan hospitals in Western Australia. SAMPLE: Patients were retained in the dataset if they spent any time on a medical, surgical or rehabilitation ward during their admission and excluded if they only spent time on other ward types, as the outcomes used in this study are only validated for these patient populations. There were 256,302 patient records in the total sample with 125,762 in the pre-test period (2006 2007) and 130,540 in the post-test period (2009-2010). RESULTS: The results showed three significant increases in observed to expected adverse outcomes on the assistant in nursing wards (failure to rescue, urinary tract infection, falls with injury), with one significant decrease (mortality). On the non-assistant in nursing wards there was one significant decrease (pneumonia) in the observed to expected adverse outcomes and one significant increase (falls with injury). Post test analysis showed that spending time on assistant in nursing wards was a significant predictor for urinary tract infection and pneumonia. For every 10% of extra time patients spent on assistant in nursing wards they had a 1% increase in the odds of developing a urinary tract infection and a 2% increase in the odds of developing pneumonia. CONCLUSION: The results suggest that the introduction of assistants in nursing into ward staffing in an additive role should be done under a protocol which clearly defines their role, scope of practice, and working relationship with registered nurses, and the impact on patient care should be monitored. PMID- 27653282 TI - A retrospective cohort study examining treatments and operative interventions for frostbite in a tertiary care hospital. AB - BACKGROUND: Frostbite is a common yet challenging injury to both diagnose and treat. McCauley's frostbite treatment protocol consists of 12 treatments that might well represent the standard of care. However, its effectiveness in preventing operative intervention has yet to be examined. Our objectives were to characterize frostbite injuries in Eastern Ontario, identify risk factors for deep injuries, and assess the protocol's efficacy in preventing operative outcomes. METHODS: This cohort study examined patients with frostbite over ten years at a tertiary care hospital. Demographics and predisposing factors were recorded. Frostbite severity was categorized into superficial or deep. Treatments were recorded, including adherence to protocol and operative outcome. RESULTS: Of the 265 frostbite patients identified, deep frostbite accounted for 56 (21.1%, 95% CI: 16.2-26.1%), of whom 20 (35.7%) had an operative outcome. Amputation occurred in 16 (28.6%) of deep injuries and debridement in 5 (8.9%). Risk factors for deep frostbite were older age (p =0.002), smoking (p <0.001), male sex (p =0.056) and alcohol abuse (p =0.056). None of the patients with deep frostbite had all 12 treatments performed. Adherence to protocol ranged from 0.0% to 48.2% per treatment. The rate of operative intervention was 7.7% in patients with deep frostbite who did not have any McCauley's frostbite treatments and ranged from 0.0% to 100.0% per treatment in those who did receive treatments. CONCLUSIONS: The frostbite protocol was not regularly followed and therefore its efficacy in preventing operative intervention could not be determined. Further, none of the individual treatments in the protocol were associated with preventing operative intervention. We recommend that future research focus on identifying effective individual treatments. PMID- 27653281 TI - A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder. AB - BACKGROUND: Exposure to ambient air pollution is widespread and may be detrimental to human brain development and a potential risk factor for Autism Spectrum Disorder (ASD). We conducted a systematic review of the human evidence on the relationship between ASD and exposure to all airborne pollutants, including particulate matter air pollutants and others (e.g. pesticides and metals). OBJECTIVE: To answer the question: "is developmental exposure to air pollution associated with ASD?" METHODS: We conducted a comprehensive search of the literature, identified relevant studies using inclusion/exclusion criteria pre-specified in our protocol (registered in PROSPERO, CRD # 42015017890), evaluated the potential risk of bias for each included study and identified an appropriate subset of studies to combine in a meta-analysis. We then rated the overall quality and strength of the evidence collectively across all air pollutants. RESULTS: Of 1,158 total references identified, 23 human studies met our inclusion criteria (17 case-control, 4 ecological, 2 cohort). Risk of bias was generally low across studies for most domains; study limitations were related to potential confounding and accuracy of exposure assessment methods. We rated the quality of the body of evidence across all air pollutants as "moderate." From our meta-analysis, we found statistically significant summary odds ratios (ORs) of 1.07 (95% CI: 1.06, 1.08) per 10-MUg/m3 increase in PM10 exposure (n = 6 studies) and 2.32 (95% CI: 2.15, 2.51) per 10-MUg/m3 increase in PM2.5 exposure (n = 3 studies). For pollutants not included in a meta-analysis, we collectively evaluated evidence from each study in rating the strength and quality of overall evidence considering factors such as inconsistency, imprecision, and evidence of dose-response. All included studies generally showed increased risk of ASD with increasing exposure to air pollution, although not consistently across all chemical components. CONCLUSION: After considering strengths and limitations of the body of research, we concluded that there is "limited evidence of toxicity" for the association between early life exposure to air pollution as a whole and diagnosis of ASD. The strongest evidence was between prenatal exposure to particulate matter and ASD. However, the small number of studies in the meta analysis and unexplained statistical heterogeneity across the individual study estimates means that the effect could be larger or smaller (including not significant) than these studies estimate. Our research supports the need for health protective public policy to reduce exposures to harmful airborne contaminants among pregnant women and children and suggests opportunities for optimizing future research. PMID- 27653283 TI - Effects of whey protein supplement in the elderly submitted to resistance training: systematic review and meta-analysis. AB - AIM: We performed a systematic review to map the evidence and analyze the effect of whey protein supplementation in the elderly submitted to resistance training. METHODS: A comprehensive search on Medline, LILACS, EMBASE, and the Cochrane Library for relevant publications was conducted until August 2015. The terms used in the search were: "Resistance training"; "Whey protein"; "Elderly". RESULTS: A total of 632 studies were screened. Five studies were included composing a sample of 391 patients. The supplement whey protein was associated with higher total protein ingestion 9.40 (95% CI: 4.03-14.78), and with an average change in plasma leucine concentration. The supplementation was also associated with increased mixed muscle protein synthesis 1.26 (95% CI: 0.46-2.07) compared to the control group. CONCLUSION: We observed an increase in total protein intake, resulting in increased concentration of leucine and mixed muscle protein fractional synthesis rate. PMID- 27653284 TI - A self-report version of the Ways of Responding: Reliability and validity in a clinical sample. AB - OBJECTIVE: The Ways of Responding (WOR) instrument measures compensatory skills, a central construct in some theories of the mechanism of cognitive therapy for depression. However, the instrument is time-consuming and expensive to use in community settings, because it requires trained independent judges to rate subjects' open-ended written responses to depressogenic scenarios. The present study evaluated the reliability and validity of a self-report version of the WOR (WOR-SR) in a community mental health sample with depressive symptoms (N = 467). METHOD: Subjects completed the WOR-SR, a modified version of the original WOR, and other measures of depressive symptoms, dysfunctional cognitions, functioning, quality of life, and interpersonal problems at multiple time points. RESULTS: An exploratory factor analysis confirmed the two-factor structure of the WOR-SR. The positive and negative subscales both demonstrated excellent internal consistency (Cronbach's alphas = .91) and moderate convergent validity with other measures. CONCLUSION: The WOR-SR is a reliable and valid measure of compensatory skills in patients receiving treatment for depression at community mental health centers. PMID- 27653285 TI - Inhibition of the TWEAK/Fn14 pathway attenuates autoimmune arthritis in a SKG mouse model. AB - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that is involved in pathogenesis of abnormal or disregulated inflammation. To verify how TWEAK/fibroblast growth factor-inducible gene 14 (Fn14) signals affect development of Th17 cells in arthritis, we utilized the SKG mouse, which spontaneously develops Th17-mediated autoimmune arthritis. Fn14-Fc was administered to zymosan A-induced arthritogenic SKG mice, and the effects in vivo were examined. Destruction of cartilage and bone damage was assessed by Hematoxylin and Eosin, and safranin O staining of the affected tissues. Phenotypic analysis of cells expressing inflammatory cytokines and angiogenesis related factors, and the expression of transcription factor STAT3 in the affected joints were determined by immunohistochemistry. Blockade of Fn14 with Fn14-Fc reduced the clinical and histologic scores of inflammatory arthritis in the mouse model of spontaneously developed chronic autoimmune arthritis. Fn14-Fc suppressed production of inflammatory cytokines and angiogenesis-promoting factors, such as vascular endothelial growth factor and matrix metalloproteinase 3. Moreover, blocking of the TWEAK signal inhibited expression of STAT3 as well as interleukin 17 and -21 produced by Th17 cells. These results implicate TWEAK as a potential molecular target for treatment or prevention of inflammatory arthritis and autoimmune diseases such as rheumatoid arthritis. PMID- 27653287 TI - Correction to "Best Face Forward: Crystal-Face Competition at the Ice-Water Interface". PMID- 27653286 TI - Structural Aspects of Heparan Sulfate Binding to Robo1-Ig1-2. AB - Roundabout 1, or Robo1, is a cell surface signaling molecule important in axon guidance. Its interaction with heparan sulfate (HS) and members of the Slit protein family is essential to its activity, making characterization of these interactions by structural methods, such as NMR, highly desirable. However, the fact that Robo1 is a glycosylated protein prevents employment of commonly used bacterial hosts for expression of properly glycosylated forms with the uniform 15N, 13C, and 2H labeling needed for NMR studies. Here, we apply an alternative methodology, based on labeling with a single amino acid type and high structural content NMR data, to characterize a two-domain construct of glycosylated Robo1 (Robo1-Ig1-2) interacting with a synthetic HS tetramer (IdoA-GlcNS6S-IdoA2S GlcNS6S-(CH2)5NH2). Significant chemical shift perturbations of the crosspeak from K81 on titration with the tetramer provide initial evidence for the location of a binding site and allow determination of a 255 MUM disassociation constant. The binding epitopes, bound conformation, and binding site placement of the HS tetramer have been further characterized by saturation transfer difference (STD), transferred nuclear Overhauser effect (trNOE), and paramagnetic perturbation experiments. A model of the complex has been generated using constraints derived from the various NMR experiments. Postprocessing energetic analysis of this model provides a rationale for the role each glycan residue plays in the binding event, and examination of the binding site in the context of a previous Robo-Slit structure provides a rationale for modulation of Robo-Slit interactions by HS. PMID- 27653288 TI - Gut microbiota, 1013 new pieces in the Parkinson's disease puzzle. AB - PURPOSE OF REVIEW: Gastrointestinal dysfunction is highly prevalent in Parkinson's disease and may precede motor symptoms by more than a decade. It has been proposed that the neurodegenerative cascade may actually be initiated in the gut with subsequent spreading to the brain and that gut microbiota could be involved in this process. This review provides a short introduction into the methodology of microbiome-wide association studies and discusses the recently published first comprehensive assessments of gut microbiota in Parkinson's disease. RECENT FINDINGS: Three case-control studies have studied gut microbiota composition in Parkinson's disease and all found significant differences between Parkinson's disease patients and controls. However, most of the differentially abundant taxa as well as associations of microbiota with clinical variables differed between studies. This may at least in part be explained by methodological differences between studies in terms of selection of participants, analysis pipelines, statistical analysis, and confounder control. SUMMARY: Current evidence suggests that there are alterations of gut microbiota in Parkinson's disease, but the exact nature of these changes is not established. Future larger studies should assess gut microbiota in Parkinson's disease covering diverse geographical regions, ethnicities, disease stages, and phenotypes using well-defined selection criteria for patients and controls and standardized methodology. PMID- 27653289 TI - Neurooncology: a Swiss army knife specialty. PMID- 27653290 TI - Neurologic complications of immune checkpoint inhibitors. AB - PURPOSE OF REVIEW: In recent years, advances in the understanding of the regulatory mechanisms of the immune system has led to the development of new approaches for cancer treatment. Currently, immune checkpoint inhibitors are the first successful examples of this approach and several agents that target cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) have been approved for various oncologic situations. The aim of this review is to describe the neurologic adverse event profiles for these new immune therapeutic approaches and to discuss their appropriate management. RECENT FINDINGS: The immune checkpoint inhibitor ipilimumab against CTLA-4 and nivolumab or pembrolizumab against PD-1 show a unique spectrum of toxic effects. The most common toxicities include rash, colitis, hepatitis, endocrinopathies, and pneumonitis. Neurologic side-effects are rare but include cases of immune polyneuropathies, Guillain Barre syndrome, myasthenia gravis, posterior reversible encephalopathy syndrome, aseptic meningitis, enteric neuropathy, transverse myelitis as well as immune encephalitis. SUMMARY: It is essential that neurologic immune-related adverse events are recognized and treated as soon as possible, as early treatment increases the odds of a complete recovery. PMID- 27653291 TI - The United Nations and the Urgent Need for Coordinated Global Action in the Fight Against Antimicrobial Resistance. PMID- 27653292 TI - AZALEA Trial Highlights Antibiotic Overuse in Acute Asthma Attacks. PMID- 27653293 TI - Efficacy of Local Anesthetic With Dexamethasone on the Quality of Recovery Following Total Extraperitoneal Bilateral Inguinal Hernia Repair: A Randomized Clinical Trial. AB - Importance: Quality of recovery (directly associated with patient satisfaction) is an important clinical outcome measurement and a surrogate of anesthetic/surgical care quality. Objectives: To compare the efficacy of a transversus abdominis plane (TAP) block with dexamethasone sodium phosphate and preperitoneal instillation of local anesthetic (PILA) with dexamethasone vs control on postoperative quality of recovery following a bilateral total extraperitoneal inguinal hernia repair (TEP-IHR) (>24 hours). Secondary objectives included efficacy of this technique on postoperative opioid use, nausea and vomiting, and pain scores. Design, Setting, and Participants: Conducted from November 2013 to August 2015, this randomized, prospective, single blinded study compared 2 groups (a TAP block and PILA) with a standard anesthetic technique with no regional technique (control) following bilateral TEP-IHR. This study at the Veterans Affairs Medical Center (Indianapolis, Indiana) included patients ages 18 to 80 years with an American Society of Anesthesiologists physical status of 1 to 3 scheduled for an outpatient bilateral TEP-IHR. Nurses assigning pain scores and administrating opioids for pain and staff anesthesiologists administering the Quality of Recovery-40 (QoR-40) questionnaire were blinded. Interventions: Patients randomized to receive a TAP block with local anesthetics and dexamethasone, PILA with dexamethasone, or no regional technique (3 groups). Main Outcomes and Measures: Patient's response to the QoR 40 questionnaire following a TEP-IHR surgery. Results: The mean (SD) ages in the TAP block (n = 19), PILA (n = 24), and control (n = 23) groups were 58.2 (9.4) years, 62.5 (8.1) years, and 62.9 (7.8) years, respectively. The global QoR-40 scores on postoperative day 1 for the TAP block group (median [interquartile range (IQR)], 178 [173-188]) were comparable with the control group (median [IQR], 174 [150-181]), while the PILA group had better global QoR-40 scores (median [IQR], 184 [175.5-190.75]) (P = .002). The effects of the TAP block and PILA on pain in the postoperative care unit (PACU) (median [IQR], 1 [0-5] and 3.5 [0-6.8], respectively), pain after discharge (median [IQR], 3 [2-5] and 3 [1 5.5], respectively), opiate use after discharge (median [IQR], 6.7 [5-10] and 6.7 [3.3-10], respectively), and incidence of nausea and vomiting in the PACU (4 of 19 [21.1%] and 6 of 24 [25%], respectively) were not significantly different from the control group (median [IQR], 4 [3-6] for pain scores in the PACU; 4 [3-7] for pain scores after discharge; 6.7 [3.3-10] for opioid use after discharge; and 6 of 23 [26.1%] for incidence of nausea/vomiting in the PACU). While there was a significant reduction of opioid use in the PACU in the TAP block group (median [IQR], 0 [0-1.3]) when compared with the control group (median [IQR], 4 [1.3 6.7]) (P = .001), this was not seen in the PILA group (median [IQR], 2 [0-6.4]). Conclusions and Relevance: This study demonstrates a better quality of recovery in patients' receiving PILA with dexamethasone compared with control for a TEP IHR surgery. Trial Registration: clinicaltrials.gov Identifier: NCT02036983. PMID- 27653295 TI - 21st Nantes Actualites Transplantation: "When Stem Cells Meet Immunology". AB - "When Stem Cells Meet Immunology" has been the topic of the 21st annual "Nantes Actualites en Transplantation" meeting (June 9-10, 2016, Nantes, France). This meeting brought together pioneers and leading experts in the fields of stem cells, biomaterials and immunoregulation. Presentations covered multipotent (mesenchymal and hematopoietic) and pluripotent stem cells (embryonic and induced) for regenerative medicine of incurable diseases, immunotherapy and blood transfusions. An additional focus had been immune rejections and responses of allogeneic or autologous stem cells. Conversely, stem cells are also able to directly modulate the immune response through the production of immunoregulatory molecules. Moreover, stem cells may also provide an unlimited source of immune cells (DCs, NK cells, B cells, and T cells) that can operate as "super" immune cells, for example, through genetic engineering with chimeric antigen receptors.This meeting report puts presentations into an overall context highlighting new potential biomarkers for potency prediction of mesenchymal stem cell-derived and pluripotent stem cell-derived multicellular organoids. Finally, we propose future directions arising from the flourishing encounter of stem cell and immune biology. PMID- 27653298 TI - MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy. AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Because of its clinically silent progression and lack of symptoms, detection is often difficult and invasive coronary angiography is performed routinely. To date, there are no established noninvasive biomarkers available for prediction of CAV in transplanted patients.MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that negatively regulate gene expression. As they are detectable in peripheral blood, recent studies have suggested miRNAs as biomarkers for various cardiovascular diseases. Thus, we hypothesized that circulating miRNAs may serve as noninvasive biomarkers for CAV. METHODS: To determine the regulation of circulating miRNAs, we performed miRNA profiling studies in plasma samples of OHT patients with confirmed high-degree CAV and a matched control group consisting of patients without any signs of CAV at least 5 years after OHT. Candidate miRNAs were verified by quantitative reverse transcriptase polymerase chain reaction. RESULTS: Microarray analysis revealed 5 candidate miRNAs (miR-34a, miR-98, miR 155, miR-204, miR-628-5p) that were differentially regulated in plasma samples of patients with CAV and therefore were selected for verification by quantitative reverse transcriptase polymerase chain reaction. In CAV patients, plasma levels of miR-628-5p and miR-155 were significantly increased (P = 0.001 and P = 0.028, respectively). A miR628-5p value above 1.336 was able to predict CAV with a sensitivity of 72% and a specificity of 83%. CONCLUSIONS: For the first time, the present study identifies the circulating miRNA miR-628-5p as a novel potential biomarker of CAV in patients after OHT. PMID- 27653300 TI - In Vivo Costimulation Blockade-Induced Regulatory T Cells Demonstrate Dominant and Specific Tolerance to Porcine Islet Xenografts. AB - BACKGROUND: Although islet xenotransplantation is a promising therapy for type 1 diabetes, its clinical application has been hampered by cellular rejection and the requirement for high levels of immunosuppression. The aim of this study was to determine the role of Foxp3 regulatory T (Treg) cells in costimulation blockade-induced dominant tolerance to porcine neonatal islet cell cluster (NICC) xenografts in mice. METHODS: Porcine-NICC were transplanted under the renal capsule of BALB/c or C57BL/6 recipients and given a single dose of CTLA4-Fc at the time of transplant and 4doses of anti-CD154 mAb to day 6. Depletion of Foxp3Treg cell was performed in DEpletion of REGulatory T cells mice at day 80 posttransplantation. Foxp3Treg cell from spleens of treated BALB/c mice (tolerant Treg cell), and splenocytes were cotransferred into islet transplanted nonobese diabetic background with severe combined immunodeficiency mice to assess suppressive function. RESULTS: In treated mice, increased numbers of Foxp3Treg cell were identified in the porcine-NICC xenografts, draining lymph node, and spleen. Porcine-NICC xenografts from treated mice expressed elevated levels of TGF-beta, IL-10 and IFN-gamma. Porcine-NICC xenograft tolerance was abrogated after depletion of Foxp3Treg cell. Tolerant Treg cell produced high levels of IL 10 and had diverse T cell receptor Vbeta repertoires with an oligoclonal expansion in CDR3 of T cell receptor Vbeta14. These tolerant Treg cells had the capacity to transfer dominant tolerance and specifically exhibited more potent regulatory function to porcine-NICC xenografts that naive Treg cell. CONCLUSIONS: This study demonstrated that short-term costimulation blockade-induced dominant tolerance and that Foxp3Treg cell played an essential role in its maintenance. Foxp3Treg cells were activated and had more potent regulatory function in vivo than naive Treg cells. PMID- 27653301 TI - Clinical Outcome of Patients With De Novo C1q-Binding Donor-Specific HLA Antibodies After Renal Transplantation. AB - BACKGROUND: De novo donor specific anti-HLA antibodies (dnDSA) may cause graft loss in renal transplant recipients. The capability to bind the complement may help to stratify the risk for inferior outcomes associated with dnDSA. We developed a modified C1q-binding assay and hypothesized that C1q-binding dnDSA could differentiate between indolent and harmful dnDSA causing antibody-mediated rejection (AMR) and graft loss. METHODS: We retrospectively identified 59 renal transplant recipients who developed dnDSA and had serum available and complete follow-up. All patients were analyzed for C1q-binding dnDSA at the time of dnDSA detection, and 1-year later or at time of AMR. AMR-positive patients were also tested 6 to 12 months before the event if IgG dnDSA was present. RESULTS: Thirty seven of 59 dnDSA patients developed AMR during 5.9 +/- 3.1 years follow-up. AMR positive patients had more dnDSA with a significant higher frequency of class I, a higher frequency and a higher mean fluorescence intensity value of C1q-dnDSA at all time-points. Death-censored AMR-free and allograft survivals were significantly lower in C1q-dnDSA patients. In multivariate analysis, C1q-dnDSA was an independent risk factor for AMR. CONCLUSIONS: C1q-binding dnDSA is associated with inferior outcomes, yet not in all patients. Nevertheless, C1q dnDSA was shown to be an independent risk factor of AMR and graft loss and may be a useful tool to stratify the immunological risk for AMR. PMID- 27653302 TI - [Primary malignant small bowel tumors]. AB - INTRODUCTION: Small bowel presents 75% of the gut length and 90% of the gut surface. However, primary malignant tumors of the small bowel represent only 1-3% of all malignant gastrointestinal tumors. The aim of the present paper is to offer a current review of primary malignant small bowel tumors - their epidemiology, localization, symptoms, diagnostic and treatment options. METHODS: The authors have performed a comprehensive review of databases Medline, Scopus and Google Scholar focusing on studies regarding small bowel cancer. RESULTS: The most frequent small bowel tumors are adenocarcinoma (30-40%), neuroendocrine tumors (35-44%), lymphomas (10-20%) and gastrointestinal stromal tumors (12-18%). Symptomatology is non-specific and varies widely, which is why small bowel cancer is usually diagnosed in a locally advanced stage of the disease. Diagnosis is determined through standard methods (gastroscopy, colonoscopy, CT) and complementary special diagnostic modalities (capsule enteroscopy, enteroscopy, octreotide scan, etc.). Diagnostic process with a negative outcome frequently leads to diagnostic laparoscopy/laparotomy.The treatment of small bowel cancer in patients operated in acute settings is done according to acute abdomen management guidelines. Elective surgery of small bowel cancer differs with respect to the tumor type. Adenocarcinomas and neuroendocrine tumors should be treated with surgical R0 resection with radical lymphadenectomy (and multivisceral resection if necessary). Patients with GIST should undergo en bloc resection with 2-3cm safety resection margins (lymphadenectomy is not necessary). Palliative resection of neuroendocrine tumors can be associated with a significant clinical effect. On the other hand, palliative resection of adenocarcinomas of GIST is not advocated. CONCLUSION: Small bowel cancer is an infrequent condition. Symptoms are non specific; patients are often diagnosed in an advanced stage of the disease. Achieving R0 surgical resection is usually difficult due to locally advanced stage of the disease. Besides the tumor type, patients prognosis is influenced by very late diagnosis of the tumor. KEY WORDS: primary tumor - small intestine - diagnostics - treatment options - surgical resection. PMID- 27653303 TI - [Postpancreatectomy haemorrhage (PPH), prevalence, diagnosis and management]. AB - INTRODUCTION: Postpancreatectomy haemorrhage (PPH) is considered to be the most severe specific postoperative complication following pancreatic resections and its treatment is difficult and requires coordinated interdisciplinary collaboration. PPH causes 11-38% of all post-pancreatectomy deaths. The aim of this study was to determine the prevalence of PPH in a set of patients operated on within the last 10 years, and to analyze the diagnostic methods, treatment modalities and the outcomes. METHODS: A retrospective analysis of patients undergoing pancreatic resections between 2006 and 2015. Clinically relevant PPH (types B and C) were the subject of interest. The onset, location and severity of PPH were analysed. Other factors analysed included operation diagnosis of PPH, diagnostic methods along with signs of sentinel bleeding, treatment options undertaken including the number of transfusions. 30-day, 90-day and in-hospital mortality, as well as the length of hospital stay and readmission rate were calculated. A descriptive statistical method was used. RESULTS: A total of 449 patients were operated on. Pancreatoduodenectomy (DPE) or pylorus-preserving pancreatoduodenectomy (PPPD) was done in 76.4%, left sided pancreatectomy (LPE) in 19.8% and total pancreatectomy (TPE) in 3.8%. 190 of the patients (42.3%) were women and 259 (57.7%) men, with the mean age of 61.5+/-11.1 years. A total of 23 (5.1%) PPH cases were identified, 21 (4.7%) were clinically relevant. Eight patients (35%) developed early PPH with direct reoperation, late PPH was seen in 14 patients after DPE and in one after LPE. Sentinel bleeding was present in 53.3% of late PPH cases. CT/CTA was performed in four patients with subsequent DSA performed in three. DSA identified a gastroduodenal artery stump pseudoaneurysm in one patient, which was resolved using a stent. Surgical intervention for late PPH was required in 10 patients in total, six of whom needed direct surgery due to the rapid development of circulatory instability and 3 due to inconclusive radiological management. One patient needed surgical drainage of both an abscess and haematoma. In two patients the origin of bleeding was due to a gastric ulcer, which was proven and solved endoscopically and 2 patients required conservative treatment only. The specific mortality for PPH was 17.4%. In the group of patients that suffered with any PPH following DPE and PPDPE the mortality rate was 22.2%, and 28.6% for late PPH. If late PPH developed coincidentally with postoperative pancreatic fistula (POPF), the mortality was 44%. In the early PPH group, an average of 10.1+/-2.5 transfusion units (TUs) were used with an average length of hospital stay 17.5+/-4.8 days and zero mortality in comparison to an average of 11.7+/-10 TUs and 29.9+/-14.6 days in hospital and 26.6% mortality in the late PPH group. CONCLUSION: PPH is a severe complication, which has a high mortality rate. It also often coincidentally develops with POPFs. Early clinical diagnosis with identification of its cause plays a key role in management. The use of interventional radiology in the treatment of PPH has begun to dominate other treatment modalities due to a very high success rate, and close collaboration with interventional radiologists is necessary in order to reduce the rate of surgical intervention required in PPH. KEY WORDS: haemorrhage - pancreas - resection - complications - mortality. PMID- 27653304 TI - [Quality of life after extensive pelvic surgery]. AB - INTRODUCTION: Multiorgan resections in the small pelvis are standard procedures in oncosurgery and some indications have no alternative. In advanced pelvic cancer, pelvic exenteration with en bloc resection of the involved organs and structures, including portions of the bony pelvis, is indicated. The 5-year survival rate is fairly good, around 50%, but little is known about the long-term quality of life. The aim was to describe the quality of life of long-term total pelvic exenteration survivors. METHOD: In total, 63 pelvic exenterations were performed between 2000 to 2015 at the Department of Surgery, Thomayer Hospital, First Faculty of Medicine, Charles University in Prague, mostly for primary or relapsed rectal cancer. In this retrospective cohort study, the quality of life was assessed using the EORTC QLQ-C30 (version 3.0) and the EORTC QLQ-CR29 questionnaires. The completed questionnaires were scored according to EORTC instructions. RESULTS: At the time of this survey, 24 patients after TPE were surviving longer than one year after the surgery. The five-year survival of all patients was 49%, median survival 4.6 years, and median follow-up 15 months. Most of our patients reported a good level of their physical, emotional, cognitive and social functions. Some patients reported a worse body image, and of course a worsening in their sexual life. Regarding symptom-oriented questions, some patients evaluated the necessity of more frequent care of the stomia as slightly problematic; most patients reported impotence (men) or painful sexual intercourse (women). CONCLUSION: Long-term quality of life in survivors of pelvic exenteration for rectal cancer is comparable with reported results following primary rectal cancer resection with the exception of the sexual function. The quality of life gradually improves in the course of weeks to months from the surgery. KEY WORDS: pelvic exenteration quality of life. PMID- 27653305 TI - [Circumscribed and diffuse peritonitis: severe complications in bariatric and metabolic surgery; specifics related to their diagnosis and therapy]. AB - INTRODUCTION: Cases of localized and diffuse peritonitis are severe surgical conditions. Despite expanding possibilities for the diagnosis and therapy, patients with peritonitis, its diffuse form in particular, still suffer from high morbidity and mortality. The management of this condition, both in the healthy and especially seriously ill population, is not satisfactory. Recently, we have witnessed an increase in bariatric and metabolic surgery in response to an ever rising number of extremely obese patients worldwide. Bariatric patients belong to a group of seriously ill patients with a significant risk of post-operative complications due to an infection. Although their treatment is identical to that of the normal population, a great emphasis is put on early recognition of complications, and the decision on any potential surgical revision should be actively approached, often necessitating the absence of frequently lengthy paraclinical assessments. METHODS: We conducted a retrospective analysis of 346 obese bariatric patients undergoing surgical treatment for morbid obesity between August 2011 and August 2015. RESULTS: A total of 6 patients experienced severe complications including two cases of diffuse peritonitis, two cases of localized peritonitis and two cases of intraperitoneal bleeding. One patient died after her discharge from hospital due to toxic shock caused by stomach perforation. We describe two case reports in greater detail to highlight the importance of early detection of complications and a timely surgical intervention. CONCLUSION: In principle, bariatric patients are a severely ill population where standard diagnostic procedures for post-operative complications often fail. Clinical findings and the surgeons experience are commonly the only diagnostic signs that trigger a surgical revision. In contrast, surgical treatment of post-operative complications in obese patients with peritonitis is virtually identical to that in patients with normal or slightly increased BMI. It involves thorough toilette of the abdominal cavity, lavage and drainage. Due to high morbidity and large peritoneal surface, obese patients may deteriorate rapidly. Timely surgical intervention is thus the only proper therapeutic approach, even without any, often lengthy paraclinical assessments. KEY WORDS: peritonitis - bariatric surgery - complications in bariatric surgery. PMID- 27653306 TI - [Synchronous colorectal carcinoma and non-Hodgkin lymphoma - two case reports]. AB - : Colorectal carcinoma represents an important cause of morbidity and mortality in adults, and its incidence in the Czech Republic is one of the world's highest. The basic therapeutic approach is surgery: surgical removal of the affected part of the bowel together with regional lymph nodes dissection. The lymph nodes are routinely examined by means of histopathology. In this paper, we present two patients whose histological examination of mesocolic lymph nodes revealed an infiltration by synchronous malignant B-non-Hodgkin-lymphoma. Mantle cell lymphoma was present in the first case, and small cell lymphoma CLL/SLL in the other. Relevant literature is reviewed. KEY WORDS: synchronous - malignancy - colorectal - lymphoma - lymph node. PMID- 27653307 TI - [Corpus alienum - migrating foreign body]. AB - Our case study presents a case of foreign body migration through the vascular system of the human body. The following paper is a comprehensive overview of different diagnostic approaches, extraction indications, common ways in which a foreign body can migrate via the vascular system and possible complications caused by the migration or extraction of the foreign body. PMID- 27653308 TI - [Coincidence of colonic lymphoma and gallstone ileus - case report]. AB - INTRODUCTION: Primary colonic lymphoma is a very rare malignant disease of the gastrointestinal tract, accounting for 14% of all malignant diseases in this location. It is classified in the group of extranodal lymphomas; its long-term asymptomatic progression makes it different from common colorectal carcinomas making its diagnosis very difficult, more often accidental. Gallstone ileus is quite an uncommon complication of cholecystolithiasis diagnosed with difficulty. Up to 50% of cases are diagnosed during surgery. The obturated location depends on the size of the stone, location of the conjunction between the biliary and gastrointestinal tracts, and also on any preexisting stenosis due to another unknown pathology. CASE REPORT: We present a case of an 86-year-old man treated for acute diverticulitis with typical clinical symptoms. Following further examination (colonoscopy, computed tomography) revealed a tumour-like infiltration in the sigmoid colon wall and a voluminous polyp was suspected according to the colonoscopy. Computed tomography described an obstruction by a biliary stone tumbling through the cholecystocolonic fistula. Subsequent biopsy supported the suspected malignant etiology. The patient underwent resection of the sigmoid colon sec. Hartmann; an infiltration was found in the subhepatic space, which corresponded to the described fistulisation between the biliary tract and the colon. A large 40 mm gallstone was found in the resected sigmoid colon over the stenosis and the bowel wall showed diffuse thickening with several polyps; final histopathological assessment confirmed malignant lymphoma of the plasmocytoma type. No serious complications occurred in the postoperative period; after healing, the patient was transferred to hematooncology care. CONCLUSION: The article describes the presence of two rare diseases - colonic lymphoma and gallstone ileus. Clearly, without the biliary stone obstruction in the preexisting tumorous stenosis in the sigmoid colon, the malignant hematooncology disease would not have been diagnosed. KEY WORDS: primary colonic lymphoma - gallstone ileus - complication of the cholecystolithiasis - extranodal lymphoma - acute diverticulitis. PMID- 27653309 TI - Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer. AB - BACKGROUND: Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. METHODS: In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. RESULTS: CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. CONCLUSION: Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017. PMID- 27653310 TI - Optimization and therapeutic effects of PDT mediated by ALA and MAL in the treatment of cutaneous malignant lesions: A comparative study. AB - 5-aminolevulinic acid (ALA) and its methylated ester (MAL) are the most common topical agents used in photodynamic therapy (PDT) as precursors of the photosensitizer protoporphyrin IX (PpIX). The induction of newly PpIX depends on incubation time of each photosensitizer in the tissue and the presence of high intralesional porphyrin levels is an important parameter for the PDT effectiveness. This study used laser-induced fluorescence (LIF) spectroscopy to evaluate the optimum time to light exposure of PDT mediated by ALA (20% w/w) and MAL (10% w/w) to treat malignant lesions precursors of cutaneous squamous cell carcinoma induced in mice. The therapeutic effects obtained by optimized ALA- and MAL-PDT were assessed 10 and 20 days after treatments. Higher PpIX levels were evidenced in the lesions photosensitized by ALA than MAL and according to LIF measurements the PDT irradiation was performed, respectively, at 300 and 330 minutes after ALA and MAL incubation. Histopathological analysis evidenced necrosis and epithelial atrophy after 10 days of PDT using both prodrugs, as well as reepitelization and collagen deposition at 20 days. Thus, despite the distinct concentration of ALA and MAL used in the formulation of each photosensitizing cream, PDT mediated by both photosensitizing agents obtained similar therapeutic outcomes. PMID- 27653311 TI - A case of occipital neuralgia in a vemurafenib-treated melanoma patient. PMID- 27653314 TI - Poster. PMID- 27653315 TI - Abstracts Published Only. PMID- 27653312 TI - Transfusion with packed red blood cells while awaiting lung transplantation is associated with reduced survival after lung transplantation. AB - BACKGROUND: The effect of pretransplant transfusion of red blood cells on survival after lung transplantation (LTx) has not been studied. METHODS: The UNOS database was queried from 2005 to 2013 to compare survival in recipients receiving a transfusion while on the LTx wait list. RESULTS: Of 12 283 adult patients undergoing single or bilateral LTx from May 2005 onwards, 11 801 met inclusion criteria, among whom 512 required transfusion while on the LTx wait list. Transfusion was associated with a higher mortality hazard in unadjusted Cox proportional hazards analysis (HR=1.296; 95% CI: 1.124, 1.494; P<.001), and in a multivariable Cox model (HR=1.178; 95% CI: 1.013, 1.369; P=.033) after multiple imputation was used to complete data on covariates. Propensity score matching was used to match transfusion recipients to nonrecipients on the likelihood of having received transfusions on the wait list, calculated from characteristics at the time of listing. Unadjusted Cox regression stratified on the matched pairs also demonstrated an association between transfusion receipt on the wait list and higher post-transplant mortality hazard (HR=1.494; 95% CI: 1.127, 1.979; P=.005). CONCLUSIONS: Blood transfusion while on the LTx wait list was associated with diminished patient survival after transplantation. PMID- 27653316 TI - Others. PMID- 27653319 TI - Nutrient content and nutrient availability of sorghum wet distiller's grain in comparison with the parental grain for ruminants. AB - BACKGROUND: The present study aimed to compare wet sorghum distiller's grain (WSDG) with sorghum grain (SG) in terms of: (i) chemical composition; (ii) in situ rumen degradation kinetics of organic matter (OM) and neutral detergent fiber (NDF); (iii) crude protein (CP) sub-fractions; (iv) in situ disappearance at 12 and 48 h; and (v) energy values. The WSDG intestinal digestibility (ID) of undegradable crude protein (UCP) was compared to soybean meal (SBM). RESULTS: Compared to SG, WSDG exhibited: (i) lower (P < 0.01) dry matter and non-fiber carbohydrate content, whereas the other chemical components were higher (P < 0.01); (ii) higher (P < 0.01) degradation rates of OM and NDF and lower (P < 0.01) degradable fraction of OM and NDF; (iii) lower (P < 0.05) contents of CP sub-fractions A, B1 and B2, and higher (P < 0.05) contents of B3 and C; (iv) lower (P < 0.05) protein disappearance at 12 and 48 h and higher UCP; and (v) lower (P < 0.05) energy content. The ID of UCP for WSDG was lower (P < 0.05) compared to SBM. CONCLUSION: The WSDG as a supplement provides a good source of energy. To enable its use as a protein supplement, further studies should be performed. (c) 2016 Society of Chemical Industry. PMID- 27653318 TI - PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology. AB - Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1707-1715, 2017. PMID- 27653320 TI - Osteocyte-Secreted Wnt Signaling Inhibitor Sclerostin Contributes to Beige Adipogenesis in Peripheral Fat Depots. AB - Cells of the osteoblast lineage are increasingly identified as participants in whole-body metabolism by primarily targeting pancreatic insulin secretion or consuming energy. Osteocytes, the most abundant bone cells, secrete a Wnt signaling inhibitor called sclerostin. Here we examined three mouse models expressing high sclerostin levels, achieved through constitutive or inducible loss of the stimulatory subunit of G-proteins (Gsalpha in mature osteoblasts and/or osteocytes). These mice showed progressive loss of white adipose tissue (WAT) with tendency toward increased energy expenditure but no changes in glucose or insulin metabolism. Interestingly beige adipocytes were increased extensively in both gonadal and inguinal WAT and had reduced canonical beta-catenin signaling. To determine if sclerostin directly contributes to the increased beige adipogenesis, we engineered an osteocytic cell line lacking Gsalpha which has high sclerostin secretion. Conditioned media from these cells significantly increased expression of UCP1 in primary adipocytes, and this effect was partially reduced after depletion of sclerostin from the conditioned media. Similarly, treatment of Gsalpha-deficient animals with sclerostin-neutralizing antibody partially reduced the increased UCP1 expression in WAT. Moreover, direct treatment of sclerostin to wild-type mice significantly increased UCP1 expression in WAT. These results show that osteocytes and/or osteoblasts secrete factors regulating beige adipogenesis, at least in part, through the Wnt-signaling inhibitor sclerostin. Further studies are needed to assess metabolic effects of sclerostin on adipocytes and other metabolic tissues. (c) 2016 American Society for Bone and Mineral Research. PMID- 27653322 TI - A review of software applications and non-software approaches in JAN. PMID- 27653325 TI - Fetal scalp blood sampling should be abandoned: FOR: FBS does not fulfil the principle of first do no harm. PMID- 27653327 TI - Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: FOR: The use of antenatal corticosteroids should be restricted if we are to avoid causing harm. PMID- 27653326 TI - Fetal scalp blood sampling should be abandoned: AGAINST: Fetal scalp blood sampling in conjunction with electronic fetal monitoring reduces the risk of unnecessary operative delivery. PMID- 27653328 TI - Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: AGAINST: Current use of antenatal corticosteroids effectively reduces neonatal morbidity and mortality. PMID- 27653329 TI - Re-evaluating the eVALuate study and the NICE guidelines: a personal review. PMID- 27653321 TI - Defining biotypes for depression and anxiety based on large-scale circuit dysfunction: a theoretical review of the evidence and future directions for clinical translation. AB - Complex emotional, cognitive and self-reflective functions rely on the activation and connectivity of large-scale neural circuits. These circuits offer a relevant scale of focus for conceptualizing a taxonomy for depression and anxiety based on specific profiles (or biotypes) of neural circuit dysfunction. Here, the theoretical review first outlines the current consensus as to what constitutes the organization of large-scale circuits in the human brain identified using parcellation and meta-analysis. The focus is on neural circuits implicated in resting reflection (default mode), detection of "salience," affective processing ("threat" and "reward"), "attention," and "cognitive control." Next, the current evidence regarding which type of dysfunctions in these circuits characterize depression and anxiety disorders is reviewed, with an emphasis on published meta analyses and reviews of circuit dysfunctions that have been identified in at least two well-powered case:control studies. Grounded in the review of these topics, a conceptual framework is proposed for considering neural circuit-defined "biotypes." In this framework, biotypes are defined by profiles of extent of dysfunction on each large-scale circuit. The clinical implications of a biotype approach for guiding classification and treatment of depression and anxiety is considered. Future research directions will develop the validity and clinical utility of a neural circuit biotype model that spans diagnostic categories and helps to translate neuroscience into clinical practice in the real world. PMID- 27653330 TI - Authors' reply. PMID- 27653332 TI - Re: Trends in urinary incontinence in women between 4 and 24 months postpartum in the EDEN cohort. PMID- 27653331 TI - Re: Pelvic organ function before and after laparoscopic bowel resection for rectosigmoid endometriosis: a prospective, observational study. PMID- 27653333 TI - Re: Frequency, severity and risk factors for urinary and faecal incontinence at 4 years postpartum: a prospective cohort. PMID- 27653334 TI - Authors' reply. PMID- 27653335 TI - Authors' reply. PMID- 27653336 TI - A report from #BlueJC: How to avoid excessive weight gain during pregnancy? PMID- 27653337 TI - Erratum. PMID- 27653338 TI - Centimeter-Scale Surface Interactions Using Hydrodynamic Flow Confinements. AB - We present a device and method for selective chemical interactions with immersed substrates at the centimeter-scale. Our implementations enable both, sequential and simultaneous delivery of multiple reagents to a substrate, as well as the creation of gradients of reagents on surfaces. The method is based on localizing submicroliter volumes of liquids on an immersed surface with a microfluidic probe (MFP) using a principle termed hydrodynamic flow confinement (HFC). We here show spatially defined, multiplexed surface interactions while benefiting from the probe capabilities such as non-contact scanning operation and convection-enhanced reaction kinetics. Three-layer glass-Si-glass probes were developed to implement slit-aperture and aperture-array designs. Analytical and numerical analysis helped to establish probe designs and operating parameters. Using these probes, we performed immunohistochemical analysis on individual cores of a human breast cancer tissue microarray. We applied alpha-p53 antibodies on a 2 mm diameter core within 2.5 min using a slit-aperture probe (HFC dimension: 0.3 mm * 1.2 mm). Further, multiplexed treatment of a tissue core with alpha-p53 and alpha-beta actin antibodies was performed using four adjacent HFCs created with an aperture array probe (HFC dimension: 4 * 0.3 mm * 0.25 mm). The ability of these devices and methods to perform multiplexed assays, present sequentially different liquids on surfaces, and interact with surfaces at the centimeter-scale will likely spur new and efficient surface assays. PMID- 27653339 TI - Investigating optimal accelerometer placement for energy expenditure prediction in children using a machine learning approach. AB - Accurate measurement of energy expenditure (EE) is imperative for identifying and targeting health-associated implications. Whilst numerous accelerometer-based regression equations to predict EE have been developed, there remains little consensus regarding optimal accelerometer placement. Therefore, the purpose of the present study was to validate and compare artificial neural networks (ANNs) developed from accelerometers worn on various anatomical positions, and combinations thereof, to predict EE. Twenty-seven children (15 boys; 10.8 +/- 1.1 years) participated in an incremental treadmill test and 30 min exergaming session wearing a portable gas analyser and nine ActiGraph GT3X+ accelerometers (chest and left and right wrists, hips, knees, and ankles). Age and sex-specific resting EE equations (Schofield) were used to estimate METs from the oxygen uptake measures. Using all the data from both exergames, incremental treadmill test and the transition period in between, ANNs were created and tested separately for each accelerometer and for combinations of two or more using a leave-one-out approach to predict EE compared to measured EE. Six features (mean and variance of the three accelerometer axes) were extracted within each 15 s window as inputs in the ANN. Correlations and root mean square error (RMSE) were calculated to evaluate prediction accuracy of each ANN, and repeated measures ANOVA was used to statistically compare accuracy of the ANNs. All single accelerometer ANNs and combinations of two-, three-, and four-accelerometers performed equally (r = 0.77-0.82), demonstrating higher correlations than the 9 accelerometer ANN (r = 0.69) or the Freedson linear regression equation (r = 0.75). RMSE did not differ between single-accelerometer ANNs or combinations of two, three, or four accelerometers (1.21-1.31 METs), demonstrating lower RMSEs than the 9-accelerometer ANN (1.46 METs) or Freedson equation (1.74 METs). These findings provide preliminary evidence that ANNs developed from single accelerometers mounted on various anatomical positions demonstrate equivalency in the accuracy to predict EE in a semi-structured setting, supporting the use of ANNs in improving EE prediction accuracy compared with linear regression. PMID- 27653340 TI - Linking adults and immatures of South African marine fishes. AB - The early life-history stages of fishes are poorly known, impeding acquisition of the identifications needed to monitor larval recruitment and year-class strength. A comprehensive database of COI sequences, linked to authoritatively identified voucher specimens, promises to change this situation, representing a significant advance for fisheries science. Barcode records were obtained from 2526 early larvae and pelagic eggs of fishes collected on the inshore shelf within 5 km of the KwaZulu-Natal coast, about 50 km south of Durban, South Africa. Barcodes were also obtained from 3215 adults, representing 946 South African fish species. Using the COI reference library on BOLD based on adults, 89% of the immature fishes could be identified to a species level; they represented 450 species. Most of the uncertain sequences could be assigned to a genus, family, or order; only 92 specimens (4%) were unassigned. Accumulation curves based on inference of phylogenetic diversity indicate near-completeness of the collecting effort. The entire set of adult and larval fishes included 1006 species, representing 43% of all fish species known from South African waters. However, this total included 189 species not previously recorded from this region. The fact that almost 90% of the immatures gained a species identification demonstrates the power and completeness of the DNA barcode reference library for fishes generated during the 10 years of FishBOL. PMID- 27653341 TI - On the buses. AB - Urgent care staff launched a publicity campaign last month to highlight the centralisation of children's emergency care services at Leeds General Infirmary (LGI). The move, which is advertised on local buses, is part of a L35 million reconfiguration of services at Leeds Teaching Hospitals NHS Trust over the next year. Pictured, left to right, are nursery nurse Sandra Barker, senior sister Julie Walker and paediatric staff nurse Roxanne Spoiverato, all of whom work in the LGI emergency department. According to trust plans, all children's inpatient care is being brought together at LGI while adult acute and elderly medicine services are centralising at St James's University Hospital. PMID- 27653342 TI - Use of care checklist set to become standard practice. AB - EMERGENCY NURSES must soon undertake a standardised list of clinical checks for all patients, according to proposals being considered at the Department of Health (DH). PMID- 27653343 TI - Care scandal trust staff may lose licence to provide services. AB - MID STAFFORDSHIRE NHS Foundation Trust is among the organisations that have been warned that they may lose their licences to provide healthcare services. PMID- 27653345 TI - ED under scrutiny for 'unreported breaches' of operational standard. AB - ONE OF the busiest emergency departments in England has come under scrutiny for failing to report breaches of the four-hour operational standard. PMID- 27653344 TI - Uk implementation of needlestick injury law faces three-year delay. AB - NURSES MAY have to wait up to three years before European Union legislation to protect them against needlestick injuries is implemented in the UK. PMID- 27653347 TI - Someone has died suddenly: for children and adults to read together Mary Williams Amy & Tom Someone has died suddenly: for children and adults to read together L4.99 45pp 9781906409098 1906409099 [Formula: see text]. AB - SOMEONE HAS Died suddenly is an e-resource to help children of all ages cope with the trauma of sudden death. PMID- 27653351 TI - Diary. AB - Trauma care 2010 May 10-14, Telford Further details: Gillian Robins at Trauma Care Management. Tel: 07847 124727 Email: trauma.care@stees.nhs.uk. PMID- 27653349 TI - No laughing matter. AB - THE WIDESPREAD popularity of social networking websites may lull people into a false sense of security about their safety and confidentiality. PMID- 27653352 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27653354 TI - Disaster response. AB - This article highlights the need for nurses to understand and appreciate the uniqueness of older people affected by disasters. PMID- 27653353 TI - Eye injuries. AB - The authors of this paper highlight a growing number of children's eye injuries caused by liquid detergent capsules. PMID- 27653355 TI - Emergency contraception. AB - This study of access to emergency contraception reviewed 11 trials and involved a total of 7,695 women from China, India, Sweden and the United States. PMID- 27653356 TI - Macro-economic factors influencing the architectural business model shift in the pharmaceutical industry. AB - INTRODUCTION: Technological innovations, new regulations, increasing costs of drug productions and new demands are only few key drivers of a projected alternation in the pharmaceutical industry. The purpose of this review is to understand the macro economic factors responsible for the business model revolution to possess a competitive advantage over market players. Areas covered: Existing literature on macro-economic factors changing the pharmaceutical landscape has been reviewed to present a clear image of the current market environment. Expert commentary: Literature shows that pharmaceutical companies are facing an architectural alteration, however the evidence on the rationale driving the transformation is outstanding. Merger & Acquisitions (M&A) deals and collaborations are headlining the papers. Q1 2016 did show a major slowdown in M&A deals by volume since 2013 (with deal cancellations of Pfizer and Allergan, or the downfall of Valeant), but pharmaceutical analysts remain confident that this shortfall was a consequence of the equity market volatility. It seems likely that the shift to an M&A model will become apparent during the remainder of 2016, with deal announcements of Abbott Laboratories, AbbVie and Sanofi worth USD 45billion showing the appetite of big pharma companies to shift from the fully vertical integrated business model to more horizontal business models. PMID- 27653357 TI - Current driven spin-orbit torque oscillator: ferromagnetic and antiferromagnetic coupling. AB - We consider theoretically the impact of Rashba spin-orbit coupling on spin torque oscillators (STOs) in synthetic ferromagnets and antiferromagnets that have either a bulk multilayer or a thin film structure. The synthetic magnets consist of a fixed polarizing layer and two free magnetic layers that interact through the Ruderman-Kittel-Kasuya-Yosida interaction. We determine analytically which collinear states along the easy axis that are stable, and establish numerically the phase diagram for when the system is in the STO mode and when collinear configurations are stable, respectively. It is found that the Rashba spin-orbit coupling can induce anti-damping in the vicinity of the collinear states, which assists the spin transfer torque in generating self-sustained oscillations, and that it can substantially increase the STO part of the phase diagram. Moreover, we find that the STO phase can extend deep into the antiferromagnetic regime in the presence of spin-orbit torques. PMID- 27653358 TI - Scientific journal publishing is too complex to be measured by a single metric: time to review the role of the impact factor! PMID- 27653360 TI - Mapping the global geographic potential of Zika virus spread. AB - The Americas are presently experiencing the most serious known outbreak of Zika virus (ZIKV). Here, we present a novel set of analyses using environmental characteristics, vector mosquito distributions, and socioeconomic risk factors to develop the first map to detail global ZIKV transmission risk in multiple dimensions based on ecological niche models. Our model predictions were tested against independent evaluation data sets, and all models had predictive ability significantly better than random expectations. The study addresses urgent knowledge gaps regarding (1) the potential geographic scope of the current ZIKV epidemic, (2) the global potential for spread of ZIKV, and (3) drivers of ZIKV transmission. Our analysis of potential drivers of ZIKV distributions globally identified areas vulnerable in terms of some drivers, but not for others. The results of these analyses can guide regional education and preparedness efforts, such that medical personnel will be better prepared for diagnosis of potential ZIKV cases as they appear. PMID- 27653359 TI - Mechanisms of carbapenem resistance in endemic Pseudomonas aeruginosa isolates after an SPM-1 metallo-beta-lactamase producing strain subsided in an intensive care unit of a teaching hospital in Brazil. AB - Carbapenem-resistance mechanisms are a challenge in the treatment of Pseudomonas aeruginosa infections. We investigated changes in P. aeruginosa carbapenem resistance determinants over a time period of eight years after the emergence of Sao Paulo metallo-beta-lactamase in a university hospital in Rio de Janeiro, Brazil. Patients admitted to the intensive care unit (ICU) were screened for P. aeruginosa colonisation and followed for the occurrence of infections from April 2007 to April 2008. The ICU environment was also sampled. Isolates were typed using random amplified polymorphic DNA, pulsed-field gel electrophoresis and multilocus sequence typing. Antimicrobial susceptibility was determined by disk diffusion and E-test, production of carbapenemases by a modified-CarbaNP test and presence of carbapenemase-encoding genes by polymerase chain reaction. Non carbapenemase resistance mechanisms studied included efflux and AmpC overexpression by PAbetaN and cloxacillin susceptibility enhancement, respectively, as well as oprD mutations. From 472 P. aeruginosa clinical isolates (93 patients) and 17 isolates from the ICU environment, high genotypic diversity and several international clones were observed; one environment isolate belonged to the blaSPM-1 P. aeruginosa epidemic genotype. Among isolates from infections, 10 (29%) were carbapenem resistant: none produced carbapenemases, three exhibited all non-carbapenemase mechanisms studied, six presented a combination of two mechanisms, and one exclusively displayed oprD mutations. Carbapenem-resistant P. aeruginosa displayed a polyclonal profile after the SPM-1 epidemic genotype declined. This phenomenon is connected with blaSPM-1 P. aeruginosa replaced by other carbapenem-resistant pathogens. PMID- 27653361 TI - High malaria transmission in a forested malaria focus in French Guiana: How can exophagic Anopheles darlingi thwart vector control and prevention measures? AB - In French Guiana, malaria vector control and prevention relies on indoor residual spraying and distribution of long lasting insecticidal nets. These measures are based on solid epidemiological evidence but reveal a poor understanding of the vector. The current study investigated the behaviour of both vectors and humans in relation to the ongoing prevention strategies. In 2012 and 2013, Anopheles mosquitoes were sampled outdoors at different seasons and in various time slots. The collected mosquitoes were identified and screened for Plasmodium infection. Data on human behaviour and malaria episodes were obtained from an interview. A total of 3,135 Anopheles mosquitoes were collected, of which Anopheles darlingi was the predominant species (96.2%). For the December 2012-February 2013 period, the Plasmodium vivax infection rate for An. darlingi was 7.8%, and the entomological inoculation rate was 35.7 infective bites per person per three month span. In spite of high bednet usage (95.7%) in 2012 and 2013, 52.2% and 37.0% of the participants, respectively, had at least one malaria episode. An. darlingi displayed heterogeneous biting behaviour that peaked between 20:30 and 22:30; however, 27.6% of the inhabitants were not yet protected by bednets by 21:30. The use of additional individual and collective protective measures is required to limit exposure to infective mosquito bites and reduce vector densities. PMID- 27653362 TI - Draft genome sequence of Acinetobacter pittii ST643 shared by cystic fibrosis patients. AB - Acinetobacter pittii has emerged as an important hospital pathogen that is associated with outbreaks and drug resistance. In cystic fibrosis (CF) patients, the detection of Acinetobacter spp. is rare; however, we isolated the A. pittii sequence type ST643 in several Brazilian CF patients treated in the same centre. The current study describes the draft genome of A. pittii ST643. PMID- 27653363 TI - Genome-wide analyses of HTLV-1aD strains from Cape Verde, Africa. AB - We characterised and reported the first full-length genomes of Human T-cell Lymphotropic Virus Type 1 subgroup HTLV-1aD (CV21 and CV79). This subgroup is one of the major determinants of HTLV-1 infections in North and West Africa, and recombinant strains involving this subgroup have been recently demonstrated. The CV21 and CV79 strains from Cape Verde/Africa were characterised as pure HTLV-1aD genomes, comparative analyses including HTLV-1 subtypes and subgroups revealed HTLV-1aD signatures in the envelope, pol, and pX regions. These genomes provide original information that will contribute to further studies on HTLV-1a epidemiology and evolution. PMID- 27653364 TI - Emergence of Acinetobacter baumannii ST730 carrying the blaOXA-72 gene in Brazil. AB - Over the last decade, Acinetobacter baumannii resistant to carbapenems has emerged in many medical centres and has been commonly associated with high morbimortality. In Brazil, this resistance is mainly attributed to the spread of OXA-23-producing clones and, to a lesser extent, to OXA-143-producing clones. Here, we describe, for the first time, two OXA-72-producing A. baumannii isolates in southern Brazil to a broad spectrum of antibiotics, except polymyxin B and tigecycline. Molecular typing by multilocus sequence typing (MLST) demonstrated that both OXA-72-producing isolates belong to a new sequence type (ST), ST730, which was recently identified in OXA-23-producing A. baumannii isolates in Sao Paulo, Brazil. We demonstrate that the two A. baumannii ST730 isolates carrying blaOXA-72share a common ancestral origin with the blaOXA-23producers in Brazil. This observation reinforces the importance of strain-typing methods in order to clarify the dynamics of the emergence of new clones in a geographic region. PMID- 27653366 TI - Analysis of Sogatella furcifera proteome that interact with P10 protein of Southern rice black-streaked dwarf virus. AB - Southern rice black-streaked dwarf virus (SRBSDV) is transmitted efficiently only by white-backed planthopper (WBPH, Sogatella furcifera) in a persistent propagative manner. Here we used a yeast two-hybrid system to investigate the interactions between the SRBSDV- P10 and the cDNA library of WBPH. Of 130 proteins identified as putative interactors, 28 were further tested in a retransformation analysis and beta-galactosidase assay to confirm the interaction. The full-length gene sequences of 5 candidate proteins: vesicle associated membrane protein 7 (VAMP7), vesicle transport V-SNARE protein (Vti1A), growth hormone-inducible transmembrane protein (Ghitm), nascent polypeptide associated complex subunit alpha, and ATP synthase lipid-binding protein) were amplified by 5' rapid amplification of cDNA ends (RACE) and used in a GST fusion protein pull-down assay. Three of these proteins interacted with SRBSDV-P10 in vitro experiment GST pull-down assay. In a gene expression analysis of 3 different growth stages and 6 different tissue organs of S. furcifera, the mRNA level of VAMP7 was high in adult males and gut. Vti1A was abundant in adult female, and malpighian tubule, gut and ovary. Ghitm was predominantly found in adult male and the malpighian tubule. These research findings are greatly helpful to understand the interaction between SRBSDV and insect vector. PMID- 27653367 TI - Associations between metabolic syndrome and clinical benign prostatic hyperplasia in a northern urban Han Chinese population: A prospective cohort study. AB - Biologic rationales exist for the associations between metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH). However, epidemiologic studies have yield inconsistent results. The aim of the present study was to prospectively evaluate the associations of MetS with the risk of BPH. The presence of MetS, the number of MetS components, and the individual MetS components were evaluated. After adjusting for potential confounders, MetS was associated with increased risk of BPH (HR: 1.29; 95% CI, 1.08-1.50; p < 0.001). Compared with subjects without any MetS components, the HRs were 0.88 (95% CI, 0.67-1.09; p = 0.86), 1.18 (95% CI, 0.89-1.47; p = 0.29) and 1.37 (95% CI, 1.08-1.66; p = 0.014) for subjects with 1, 2, or >=3 MetS components, and there was a biologic gradient between the number of MetS components and the risk of BPH (p-trend < 0.001). Central obesity and low high-density lipoprotein cholesterol were the two main divers of the associations between these two conditions, with HRs of 1.93 (95% CI, 1.14-2.72; p = 0.001) for central obesity, and 1.56 (95% CI, 1.08-2.04; p = 0.012) for low HDL-C. Our findings support the notion that MetS may be an important target for BPH prevention and intervention. PMID- 27653365 TI - Thyroid hormone suppresses hepatocarcinogenesis via DAPK2 and SQSTM1-dependent selective autophagy. AB - Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DEN-induced hepatotoxicity or carcinogenesis. PMID- 27653368 TI - ? PMID- 27653369 TI - ? PMID- 27653370 TI - ? PMID- 27653371 TI - ? PMID- 27653372 TI - ? PMID- 27653374 TI - Identification of miRNAs and their targets in wild tomato at moderately and acutely elevated temperatures by high-throughput sequencing and degradome analysis. AB - MicroRNAs (miRNAs) are 19-24 nucleotide (nt) noncoding RNAs that play important roles in abiotic stress responses in plants. High temperatures have been the subject of considerable attention due to their negative effects on plant growth and development. Heat-responsive miRNAs have been identified in some plants. However, there have been no reports on the global identification of miRNAs and their targets in tomato at high temperatures, especially at different elevated temperatures. Here, three small-RNA libraries and three degradome libraries were constructed from the leaves of the heat-tolerant tomato at normal, moderately and acutely elevated temperatures (26/18 degrees C, 33/33 degrees C and 40/40 degrees C, respectively). Following high-throughput sequencing, 662 conserved and 97 novel miRNAs were identified in total with 469 conserved and 91 novel miRNAs shared in the three small-RNA libraries. Of these miRNAs, 96 and 150 miRNAs were responsive to the moderately and acutely elevated temperature, respectively. Following degradome sequencing, 349 sequences were identified as targets of 138 conserved miRNAs, and 13 sequences were identified as targets of eight novel miRNAs. The expression levels of seven miRNAs and six target genes obtained by quantitative real-time PCR (qRT-PCR) were largely consistent with the sequencing results. This study enriches the number of heat-responsive miRNAs and lays a foundation for the elucidation of the miRNA-mediated regulatory mechanism in tomatoes at elevated temperatures. PMID- 27653375 TI - Non-linear scaling of a musculoskeletal model of the lower limb using statistical shape models. AB - Accurate muscle geometry for musculoskeletal models is important to enable accurate subject-specific simulations. Commonly, linear scaling is used to obtain individualised muscle geometry. More advanced methods include non-linear scaling using segmented bone surfaces and manual or semi-automatic digitisation of muscle paths from medical images. In this study, a new scaling method combining non linear scaling with reconstructions of bone surfaces using statistical shape modelling is presented. Statistical Shape Models (SSMs) of femur and tibia/fibula were used to reconstruct bone surfaces of nine subjects. Reference models were created by morphing manually digitised muscle paths to mean shapes of the SSMs using non-linear transformations and inter-subject variability was calculated. Subject-specific models of muscle attachment and via points were created from three reference models. The accuracy was evaluated by calculating the differences between the scaled and manually digitised models. The points defining the muscle paths showed large inter-subject variability at the thigh and shank - up to 26mm; this was found to limit the accuracy of all studied scaling methods. Errors for the subject-specific muscle point reconstructions of the thigh could be decreased by 9% to 20% by using the non-linear scaling compared to a typical linear scaling method. We conclude that the proposed non-linear scaling method is more accurate than linear scaling methods. Thus, when combined with the ability to reconstruct bone surfaces from incomplete or scattered geometry data using statistical shape models our proposed method is an alternative to linear scaling methods. PMID- 27653376 TI - The effect of the extensor mechanism on maximum isometric fingertip forces: A numerical study on the index finger. AB - The extensor mechanism is a tendinous network connecting intrinsic and extrinsic muscles of the finger and its function has not yet been fully understood. The goal of this study was to assess the effect of the extensor mechanism on the maximum isometric fingertip forces - a parameter which is essential for grasping. For this purpose, maximum fingertip forces in all directions (i.e. feasible force sets) of two musculoskeletal models of the index finger were compared: the wEM model included a full representation of the extensor mechanism, whereas in the noEM model the extensor mechanism was replaced by a single extensor tendon without connectivity to intrinsic muscles. The feasible force sets were computed in the flexion-extension plane for nine postures. Forces in four predefined directions (palmar, proximal, dorsal, and distal), and the peak resultant forces were evaluated. Averaged forces in all four predefined directions were considerably larger in the wEM model (+187.6%). However, peak resultant forces were slightly lower in the wEM model (-4.3% on average). The general advantage of the wEM model could be explained by co-contraction of intrinsic and extrinsic extensor muscles which allowed reaching larger activation levels of the extrinsic flexors. Only within a narrow range of force directions the co-contraction of intrinsic muscles limited the fingertip forces and lead to lower peak resultant forces in the wEM model. Rather than maximizing peak resultant forces, it appears that the extensor mechanism is a sophisticated tool for increasing maximum fingertip forces over a broad range of postures and force directions - making the finger more versatile during grasping. PMID- 27653377 TI - Decrease of the electrical potentials measured on the surface of the knee and produced by cartilage compression during successive loading cycles. AB - Electroarthrography (EAG) is a new technique for measuring electrical potentials appearing on the knee surface during loading that reflects cartilage quality and joint contact force. Our objective was to investigate the evolution of EAG signals during successive loading cycles. The study was conducted on 20 standing subjects who shifted their body weight to achieve knee loading. Their EAG signals were recorded during 10 successive loading cycles, and during a subsequent sequence of 10 cycles recorded after a 15min exercise period. Multiple linear regression models estimated the electro-mechanical ratio (EMR) interpreting the ability of cartilage to generate a certain potential for a given ground reaction force by taking into account this force and the center of pressure displacements during unipedal stance. The results showed that the EMR values slowly decreased with successive cycles: during the initial sequence, the correlation coefficients between EMR values and sequence numbers were significant at 3 of the 4 electrode sites (p<0.05); for the post-exercise sequence, the EMR values still decreased and were significantly lower than during the initial sequence (p<0.001). The reduction of EMR values could arise from muscle activity and habituation of the stretch reflex, and also from the time dependent electromechanical properties of cartilage. In conclusion, refraining from physical activity before the EAG measurements is important to improve measurement repeatability because of the EMR decrease. The electromechanical model confirmed the role of EAG as a natural sensor of the changes in the knee contact force and also improved EAG measurement accuracy. PMID- 27653378 TI - Identification of tonsillar CD4+CD25-LAG3+ T cells as naturally occurring IL-10 producing regulatory T cells in human lymphoid tissue. AB - IL-10-producing regulatory T cells (IL-10-producing Tregs) are one of the regulatory T cell subsets characterized by the production of high amounts of IL 10, the lack of FOXP3 expression and the strong immunosuppressive capabilities. IL-10-producing Tregs have been primarily reported as induced populations thus far, in part because identifying naturally occurring IL-10-producing Tregs was difficult due to the lack of definitive surface markers. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue that we have identified as being expressed on IL 10 producing Tregs. In human PBMC, LAG3 combined with CD49b efficiently identifies IL-10-producing Tregs. However, naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue have not been described. In this report, we identified CD4+CD25-LAG3+ T cells in human tonsil. This T cell subset produced high amounts of IL-10 and expressed low levels of FOXP3. Surface markers and microarray analysis revealed that this is a distinct tonsillar CD4+ T cell subset. CD4+CD25-LAG3+ T cells expressed interleukin 10 (IL10), PR/SET domain 1 (PRDM1), and CD274 at high levels and chemokine receptor 5 (CXCR5) at low levels. CD4+CD25-LAG3+ T cells suppressed antibody production more efficiently than CD4+CD25+ T cells, and CD4+CD25-LAG3+ T cells induced B cell apoptosis. Moreover, analysis of humanized mice revealed that this cell subset suppressed a graft versus-host disease (GVHD) reaction in vivo. Our study reveals the existence of naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue and their function in immune regulation. PMID- 27653379 TI - A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques. AB - As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types. PMID- 27653380 TI - Value of 18F-FDG heterogeneity for discerning metastatic from benign lymph nodes in nasopharyngeal carcinoma patients with suspected recurrence. AB - OBJECTIVE: This study investigated the value of fluorine-18 fludeoxyglucose (18F FDG) heterogeneity as an indicator of metastatic lymph nodes (LNs) in patients with nasopharyngeal carcinoma (NPC). We further assessed whether addition of this parameter improves diagnostic performance beyond that provided by maximum standardized uptake value (SUVmax). METHODS: We analyzed 74 LNs that were suspicious for metastasis. These LNs were measured for coefficient of variation (CV) of 18F-FDG uptake, which was used as a parameter for 18F-FDG heterogeneity. RESULTS: Multivariate logistic regression analyses revealed that a high CV (hazard ratio, 20.97; 95% confidence interval, 2.26-194.62; p = 0.007) was an independent predictor of metastatic LNs. However, receiver-operating characteristic curve analysis (p = 0.278) and net reclassification (p = 0.539) were unable to show improved diagnostic performance by addition of CV to SUVmax. CONCLUSION: High CV of 18F-FDG uptake is an independent risk factor for metastatic LNs in patients with NPC displaying suspicious LNs following treatment. Advances in knowledge: Heterogeneity of 18F-FDG uptake has a potential as a biomarker of metastatic LNs. PMID- 27653381 TI - Erratum to 'The TIDieR checklist will benefit the physiotherapy profession' [Manual Therapy 24C (2016) V-VI]. PMID- 27653382 TI - The Role of PIEZO2 in Human Mechanosensation. AB - BACKGROUND: The senses of touch and proprioception evoke a range of perceptions and rely on the ability to detect and transduce mechanical force. The molecular and neural mechanisms underlying these sensory functions remain poorly defined. The stretch-gated ion channel PIEZO2 has been shown to be essential for aspects of mechanosensation in model organisms. METHODS: We performed whole-exome sequencing analysis in two patients who had unique neuromuscular and skeletal symptoms, including progressive scoliosis, that did not conform to standard diagnostic classification. In vitro and messenger RNA assays, functional brain imaging, and psychophysical and kinematic tests were used to establish the effect of the genetic variants on protein function and somatosensation. RESULTS: Each patient carried compound-inactivating variants in PIEZO2, and each had a selective loss of discriminative touch perception but nevertheless responded to specific types of gentle mechanical stimulation on hairy skin. The patients had profoundly decreased proprioception leading to ataxia and dysmetria that were markedly worse in the absence of visual cues. However, they had the ability to perform a range of tasks, such as walking, talking, and writing, that are considered to rely heavily on proprioception. CONCLUSIONS: Our results show that PIEZO2 is a determinant of mechanosensation in humans. (Funded by the National Institutes of Health Intramural Research Program.). PMID- 27653383 TI - Recent Internet Use and Associations with Clinical Outcomes among Patients Entering Addiction Treatment Involved in a Web-Delivered Psychosocial Intervention Study. AB - The acceptability and clinical impact of a web-based intervention among patients entering addiction treatment who lack recent internet access are unclear. This secondary analysis of a national multisite treatment study (NIDA Clinical Trials Network-0044) assessed for acceptability and clinical impact of a web-based psychosocial intervention among participants enrolling in community-based, outpatient addiction treatment programs. Participants were randomly assigned to 12 weeks of a web-based therapeutic education system (TES) based on the community reinforcement approach plus contingency management versus treatment as usual (TAU). Demographic and clinical characteristics, and treatment outcomes were compared among participants with recent internet access in the 90 days preceding enrollment (N = 374) and without internet access (N = 133). Primary outcome variables included (1) acceptability of TES (i.e., module completion; acceptability of web-based intervention) and (2) clinical impact (i.e., self reported abstinence confirmed by urine drug/breath alcohol tests; retention measured as time to dropout). Internet use was common (74 %) and was more likely among younger (18-49 years old) participants and those who completed high school (p < .001). Participants randomized to TES (n = 255) without baseline internet access rated the acceptability of TES modules significantly higher than those with internet access (t = 2.49, df = 218, p = .01). There was a near significant interaction between treatment, baseline abstinence, and internet access on time to dropout (chi 2(1) = 3.8089, p = .051). TES was associated with better retention among participants not abstinent at baseline who had internet access (X 2(1) = 6.69, p = .01). These findings demonstrate high acceptability of this web based intervention among participants that lacked recent internet access. PMID- 27653385 TI - Physical and/or Cognitive Impairment, Out-of-Pocket Spending, and Medicaid Entry among Older Adults. AB - While Medicare provides health insurance coverage for those over 65 years of age, many still are underinsured, experiencing substantial out-of-pocket costs for covered and non-covered services as a proportion of their income. Using the Health and Retirement Study (HRS), this study found that being underinsured is a significant predictor of entering into Medicaid coverage over a 16-year period. The rate of entering Medicaid was almost twice as high for those who were underinsured and with physical and/or cognitive impairment than those who were not, while supplemental health insurance reduced the rate of entering Medicaid by 30 %. Providing more comprehensive coverage through the traditional Medicare program, including a ceiling on out-of-pocket expenditures or targeted support for those with physical or cognitive impairment, could postpone becoming covered by Medicaid and yield savings in Medicaid. PMID- 27653384 TI - Accelerated Health Declines among African Americans in the USA. AB - The weathering hypothesis, an explanation for race disparities in the USA, asserts that the health of African Americans begin to deteriorate prematurely compared to whites as a consequence of long-term exposure to social and environmental risk factors. Using data from 2000-2009 National Health Interview Surveys (NHIS), we sought to describe differences in age-related health outcomes in 619,130 African Americans and whites. Outcome measures included hypertension, diabetes, stroke, and cardiovascular disease. Using a mixed models approach to age-period-cohort analysis, we calculated age- and race-specific prevalence rates that accounted for the complex sampling design of NHIS. African Americans exhibited higher prevalence rates of hypertension, diabetes, and stroke than whites across all age groups. Consistent with the weathering hypothesis, African Americans exhibited equivalent prevalence rates for these three conditions 10 years earlier than whites. This suggests that African Americans are acquiring age related conditions prematurely compared to whites. PMID- 27653386 TI - Dietary Resistant Starch Supplementation Increases High-Density Lipoprotein Particle Number in Pigs Fed a Western Diet. AB - Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total HDL particle number. PMID- 27653387 TI - War Metaphors in Health Care: What Are They Good For? PMID- 27653388 TI - Healing Without Waging War: Beyond Military Metaphors in Medicine and HIV Cure Research. AB - Military metaphors are pervasive in biomedicine, including HIV research. Rooted in the mind set that regards pathogens as enemies to be defeated, terms such as "shock and kill" have become widely accepted idioms within HIV cure research. Such language and symbolism must be critically examined as they may be especially problematic when used to express scientific ideas within emerging health-related fields. In this article, philosophical analysis and an interdisciplinary literature review utilizing key texts from sociology, anthropology, history, and Chinese and African studies were conducted to investigate the current proliferation of military metaphors. We found the use of these metaphors to be ironic, unfortunate, and unnecessary. To overcome military metaphors we propose to (1) give them less aggressive meanings, and/or (2) replace them with more peaceful metaphors. Building on previous authors' work, we argue for the increased use of "journey" (and related) metaphors as meaningful, cross culturally appropriate alternatives to military metaphors. PMID- 27653389 TI - Metaphors as Equipment for Living. PMID- 27653390 TI - Journeys as Shared Human Experiences. PMID- 27653391 TI - Military Metaphors in Health Care: Who Are We Actually Trying to Help? PMID- 27653392 TI - Medical Metaphors Matter: Experiments Can Determine the Impact of Metaphors on Bioethical Issues. PMID- 27653393 TI - Military Metaphors and Their Contribution to the Problems of Overdiagnosis and Overtreatment in the "War" Against Cancer. PMID- 27653394 TI - Asking More of Our Metaphors: Narrative Strategies to End the "War on Alzheimer's" and Humanize Cognitive Aging. PMID- 27653395 TI - Killing the Pain and Battling the Lethargy: Misleading Military Metaphors in Palliative Care. PMID- 27653396 TI - Of HIV, Kings, and Cures: Troubling the Apocryphal Apothecary. PMID- 27653397 TI - HIV/AIDS: The Challenging Journey. PMID- 27653398 TI - Governance of Transnational Global Health Research Consortia and Health Equity. AB - Global health research partnerships are increasingly taking the form of consortia of institutions from high-income countries and low- and middle-income countries that undertake programs of research. These partnerships differ from collaborations that carry out single projects in the multiplicity of their goals, scope of their activities, and nature of their management. Although such consortia typically aim to reduce health disparities between and within countries, what is required for them to do so has not been clearly defined. This article takes a conceptual approach to explore how the governance of transnational global health research consortia should be structured to advance health equity. To do so, it applies an account called shared health governance to derive procedural and substantive guidance. A checklist based on this guidance is proposed to assist research consortia determine where their governance practices strongly promote equity and where they may fall short. PMID- 27653399 TI - Justice and Global Health Research. PMID- 27653400 TI - More Than One Way to Be Global: Globalization of Research and the Contest of Ideas. PMID- 27653401 TI - Deliberation to Promote Shared Sovereignty in Health Research: Four Questions to Clarify Goals, Methods, and Scope. PMID- 27653402 TI - Consistency in the Structure of Global Health Research Consortia. PMID- 27653403 TI - No "Shared Governance" Without Attention to Law, Broadly Conceived. PMID- 27653404 TI - Global Health Research Partnerships-Shared Responsibility Regulative Model. PMID- 27653405 TI - Governance and Standards in International Clinical Research: The Role of Transnational Consortia. PMID- 27653406 TI - The Role of Development Research Funders in Promoting Equity in Research Consortia. PMID- 27653407 TI - Shared Governance Embedded in Population Ethics Can Enhance Health Equity Research at Both Micro and Macro Levels. PMID- 27653408 TI - When a Clinical Trial Is the Only Option. PMID- 27653409 TI - "Respect for Persons," Not "Respect for Citizens". PMID- 27653410 TI - The Potentially High Cost of a Free Clinical Trial. PMID- 27653411 TI - Contextualizing "Choice" for Undocumented Immigrants in U.S. Clinical Trials Research. PMID- 27653412 TI - Studying the Role of Financial Incentives to Promote Hepatitis B Vaccination in a Community Clinic. PMID- 27653413 TI - Treatment Incentives and the Nature of the Doctor-Patient Relationship. PMID- 27653414 TI - The Ethics of Studying Financial Incentives in Public Health Implementation: Study Design Challenges. PMID- 27653416 TI - Response to Open Peer Commentaries on "Human Germline CRISPR-Cas Modification: Toward a Regulatory Framework". PMID- 27653415 TI - You Can Lead a Horse to Water, But Can You Pay to Make Him Drink? An Ethical Analysis of Research on Using Incentives to Promote Patient Health. PMID- 27653419 TI - Real-Time Kinetic Probes Support Monothiol Glutaredoxins As Intermediate Carriers in Fe-S Cluster Biosynthetic Pathways. AB - Iron-sulfur (Fe-S) clusters are protein cofactors that are required for many essential cellular functions. Fe-S clusters are synthesized and inserted into target proteins by an elaborate biosynthetic process. The insensitivity of most Fe-S assembly and transfer assays requires high concentrations for components and places major limits on reaction complexity. Recently, fluorophore labels were shown to be effective at reporting cluster content for Fe-S proteins. Here, the incorporation of this labeling approach allowed the design and interrogation of complex Fe-S cluster biosynthetic reactions that mimic in vivo conditions. A bacterial Fe-S assembly complex, composed of the cysteine desulfurase IscS and scaffold protein IscU, was used to generate [2Fe-2S] clusters for transfer to mixtures of putative intermediate carrier and acceptor proteins. The focus of this study was to test whether the monothiol glutaredoxin, Grx4, functions as an obligate [2Fe-2S] carrier protein in the Fe-S cluster distribution network. Interestingly, [2Fe-2S] clusters generated by the IscS-IscU complex transferred to Grx4 at rates comparable to previous assays using uncomplexed IscU as a cluster source in chaperone-assisted transfer reactions. Further, we provide evidence that [2Fe-2S]-Grx4 delivers clusters to multiple classes of Fe-S targets via direct ligand exchange in a process that is both dynamic and reversible. Global fits of cluster transfer kinetics support a model in which Grx4 outcompetes terminal target proteins for IscU-bound [2Fe-2S] clusters and functions as an intermediate cluster carrier. Overall, these studies demonstrate the power of chemically conjugated fluorophore reporters for unraveling mechanistic details of biological metal cofactor assembly and distribution networks. PMID- 27653420 TI - Simultaneous liver kidney transplantation. AB - PURPOSE OF REVIEW: Simultaneous liver kidney transplantation (SLK) has taken center stage since the initiation of the new kidney allocation system (KAS). This review places SLK in the context of the changing landscape of organ allocation. RECENT FINDINGS: The introduction of the Mayo End-Stage Liver Disease score into liver allocation policy in 2002 resulted in a significant increase in the number of SLKs performed in the United States. Except for a brief respite in 2009, the rate of SLK has continued to increase with 2015 seeing 626 SLKs. KAS did not mandate sharing kidneys with regionally shared livers. It was anticipated this would reduce the number of SLKs. Additionally, the Kidney Donor Profile Index in KAS made possible a more granular assessment of the quality of the kidneys being allocated to SLK recipients. This revealed that nearly 50% of Kidney Donor Profile Index kidneys 0.35 or less, those to be allocated to children, were given to SLK recipients and that a significant proportion of them may not need a kidney. SUMMARY: Medical eligibility criteria, rules for the allocation of kidneys simultaneously with livers, and the establishment of a safety net, will provide nephrologists with the framework and authority to decide which liver disease patients truly need a kidney. PMID- 27653421 TI - Current status of pancreas transplantation. AB - PURPOSE OF REVIEW: To review recent pancreas transplantation outcomes and indications and describe studies of the impact of pancreas transplant upon patient survival and secondary complications. RECENT FINDINGS: A number of surgical advances have occurred that have improved the early success rate of transplant, and modern immunosuppressive strategies have improved the rate of longer term allograft survival. Pancreas transplant is associated with a mortality benefit when performed in patients with end-stage renal disease in combination with kidney transplant, but questions regarding the impact upon secondary diabetic complications together with the risk assumed by the surgical procedure and the attendant immunosuppression in the nonuremic patient may have tempered enthusiasm for broader expansion of transplantation. Thus, despite these advances, the number of pancreas transplants performed annually is falling consistently. Efforts to define optimal donor and recipient characteristics and understand the pathophysiological impact of pancreas transplant are active areas of research that may lead to greater expansion of pancreas transplant in the future. SUMMARY: The review summarizes these advances, including the utilization patterns of pancreas transplant and current concepts of patient selection and graft monitoring, and places into perspective the current and future role of pancreas transplantation as a therapeutic option in diabetes. PMID- 27653422 TI - Getting Pharmacogenomics Into the Clinic. PMID- 27653423 TI - Breakthrough cancer pain: twenty-five years of study. AB - Breakthrough cancer pain (BTcP) is an episode of severe pain that "breaks through" a period of persistent pain at least partly controlled by a stable opioid regimen. Although mentioned in the literature decades ago, it has been only 25 years since the first effort to define and measure it. Controversy about the definition of BTcP continues despite an international effort to achieve consensus. Nevertheless, common approaches to measurement of BTcP have led to a robust literature, including many surveys that have described prevalence, characteristics, and association with adverse outcomes. Measurement also has been important for clinical trials of new drug formulations specifically designed for BTcP. Several approaches have been reported in the literature, although most of them have never been substantiated with appropriate studies. Administration of an opioid as needed is the most common treatment. Twenty-five years of research has produced a more refined understanding of the safety and efficacy of oral opioids in this context, and provided the clinical trials data necessary to attain regulatory approval of multiple new formulations specifically developed for BTcP. Transmucosal formulations of fentanyl may provide meaningful analgesia within 5 to 15 minutes. Given the difference in cost, transmucosal formulations should be considered in a subset of patients with BTcP, including those with pain that are not adequately controlled with an oral drug and those with distress associated with the rapid pain onset. The long-term use of opioids for BTcP remains to be clarified. Future studies should assess the potential of personalized treatment of BTcP. PMID- 27653424 TI - Incentive and Restriction in Combination-Make Food Assistance Healthier With Carrots and Sticks. PMID- 27653425 TI - Urologist-Level Correlation in the Use of Observation for Low- and High-Risk Prostate Cancer. AB - Importance: The reporting of individual urologist rates of observation for localized prostate cancer may be a valuable performance measure with important downstream implications for patient and payer stakeholder groups. However, few studies have examined the urologist-level variation in the use of observation across all risk strata of prostate cancer. Objectives: To measure variation in the use of observation at the urologist level by disease risk strata and to evaluate the association between the urologist-level rates of observation for men with low-risk and high-risk prostate cancer. Design, Setting, and Participants: With the use of linked Surveillance, Epidemiology, and End Results (SEER) Medicare data, a population-based study of men diagnosed with prostate cancer from January 1, 2004, to December 31, 2009, was performed in SEER catchment areas of the United States. A total of 57 639 men with prostate cancer with 1884 diagnosing urologists were identified. Data were analyzed from October 1 to December 31, 2015. Main Outcomes and Measures: The main outcome was observation, which is defined as the absence of definitive treatment within 1 year of diagnosis. In each risk stratum, a multivariable mixed-effects model was fit to characterize associations between observation and selected patient characteristics. From these models, the estimated probability of observation was calculated for each urologist within each risk stratum, and the association between the physician-level estimated rates of observation for low-risk and high risk disease was assessed. Results: Among the 57 639 men included in the study, the estimated probability of observation for low-risk disease varied impressively (mean, 27.8%; range, 5.1%-71.2%) at the individual urologist level. Considerably less urologist-level variation was seen in the use of observation for intermediate-risk disease (11.1%; range, 4.8%-31.5%) and high-risk disease (5.8%; range, 3.2%-16.5%). Furthermore, the estimated rates of observation for low- and high-risk disease were correlated at the urologist level (Spearman rho = 0.17; P < .001). A comparable correlation was likewise observed among urologists with high-volume prostate cancer practices (Spearman rho = 0.24; P < .001). Conclusions and Relevance: Considerable urologist-level variation is seen in the use of observation for men with low-risk prostate cancer. More important, the use of observation for low-risk and high-risk patients with prostate cancer is correlated at the urologist level. This study reveals the strikingly variable use of observation among US urologists and establishes a framework for the use of urologist-level treatment signatures as a quality measure in the emerging value based health care environment. PMID- 27653426 TI - Lactobacillus pentosus expressing porcine lactoferrin elevates antibacterial activity and improves the efficacy of vaccination against Aujeszky's disease. AB - In this study, Lactobacillus pentosus expressing porcine lactoferrin (pLF) was tested for in vitro antibacterial activity and for its ability to enhance immunity induced by an orally administered Aujeszky's disease virus (ADV) vaccine. The cDNA encoding N-terminus of pLF was cloned into a Lactobacillus specific plasmid to produce L. pentosus pLF expressing transformants (pPG612.1 pLFN/ L. pentosus). The antimicrobial activity of the recombinant pLF protein inhibited bacterial growth in vitro. The supernatant of pPG612.1-pLF-N/L. pentosus had an inhibitory effect on Staphylococcus aureus strain CVCC26003, Bacillus subtilis strain CVCC63501, Escherichia coli strain CVCC10141 and Salmonella enterica ssp. enterica Choleraesuis strain CVCC79102, while it did not inhibit the growth of Lactobacillus casei strain ATCC393. A mouse model was established to test the effectiveness of the orally administered probiotic L. pentosus recombinant strain in the gastrointestinal tract. Mice were immunised with an attenuated porcine Aujeszky's disease virus (ADV) vaccine. Serum antibody levels determined using a mouse Aujeszky's disease IgG ELISA showed that IgG levels were significantly higher in the pPG612.1-pLFN/L. pentosus group than in the PBS and Lactobacillus pentosus groups at days 7 and 21 (P < 0.01) and at day 14 (P < 0.05), indicating that this oral recombinant strain can improve the effectiveness of the vaccine and play a role in immune enhancement through humoral immunity. These results suggest that the recombinant Lactobacillus pentosus not only has the beneficial characteristics of lactic acid bacteria but also produces biologically functional lactoferrin. PMID- 27653427 TI - Effects of subclinical Mycobacterium avium ssp. paratuberculosis infection on some physiological parameters, health status and production in dairy cows. AB - Milk yield, milk ingredients, health and other, production-related parameters of subclinically infected, Mycobacterium avium ssp. paratuberculosis (MAP-) shedding (positive faecal PCR, n = 20) and non-shedding (negative faecal PCR, n = 10) dairy cows were compared in the period from 10 days prepartum to 120 days postpartum. Body condition, rumen fill and faeces scores were lower in the MAP shedding cows. There was no significant difference in plasma or urine metabolic parameters between the groups. Milk yield and lactose content tended to be lower (P = 0.074 and 0.077, respectively), somatic cell count tended to be higher (P = 0.097), while milk fat content was significantly higher (P = 0.006) in MAP shedding cows than in the controls. Milk protein content did not differ between the groups. All other health and production parameters [number of reproductive tract treatments, number of udder treatments, number of artificial inseminations (AIs), calving interval, and service period] were significantly better in the control group. It is concluded that MAP infection, even in a subclinical form, has a significant impact on some production and health parameters of dairy cows. PMID- 27653428 TI - Comparative clinical evaluation of tacrolimus and cyclosporine eye drops for the treatment of canine keratoconjunctivitis sicca. AB - The aim of this study was to evaluate the efficacy of tacrolimus eye drops in alleviating the clinical symptoms of canine keratoconjunctivitis sicca (KCS) and to compare this efficacy with that of cyclosporine. The clinical study was conducted on 40 dogs diagnosed with idiopathic KCS. The dogs were divided into two groups of 20 animals each. In Group I, 0.75% cyclosporine eye drops were administered three times a day, while in Group II 0.02% tacrolimus eye drops were given twice daily. In addition, each group was subdivided into three subgroups based on the results of Schirmer tear test I (STT I). Clinical and ophthalmologic examinations were performed prior to the treatment as well as after one and two months of therapy. The application of both tacrolimus and cyclosporine resulted in a significant reduction of neovascularisation after the first and second month of treatment (P < 0.05, P < 0.001); however, in moderate and advanced stages, the observed efficacy of tacrolimus was higher. Across all patients, a significant increase in STT I values was observed after both the first and second month of treatment with tacrolimus (P < 0.01), as well as after two months of treatment with cyclosporine (P < 0.05). In both groups, some patients were observed to exhibit inhibited development of pigmentation, but an analysis of particular clinical cases and statistical data revealed no statistically significant discrepancies in the course of the study. In cases of advanced canine KCS, the efficacy of tacrolimus may be higher than that of cyclosporine. PMID- 27653429 TI - Congenital and acquired anomalies of the caudal vertebrae in dogs: Radiographic classification and prevalence evaluation. AB - A prospective study to create radiographic classification of caudal vertebral anomalies in dogs was performed and the prevalence of the disorders estimated. Radiographic examination of the caudal vertebrae was performed in 595 client owned dogs undergoing routine radiological examination of the hip joints. Anomalies of the caudal vertebrae were divided into four groups: (1) congenital anomalies with aberrant fusion of the vertebral epiphysis, like hemivertebra, block or transitional vertebra; (2) morphological anomalies like vertebra curva and dysplastic vertebral epiphysis; (3) post-traumatic changes, represented by fracture or luxation; and (4) degenerative changes, represented by spondylosis, osteophyte formation and mineralisation of intervertebral spaces. A total of 303 caudal vertebral anomalies were detected in 259 dogs (43.53% of all dogs examined). A single type of vertebral anomaly was present in 215 dogs and a combination of two pathologies was recorded in 44 dogs, which represents 83.01% and 16.99%, respectively, of the affected dogs. Congenital anomaly was present in 11.09% of the dogs examined. Sacrocaudal transitional vertebra was the most common congenital anomaly, present in 12.74% of the affected dogs. Radiographic examination of the caudal vertebrae is recommended as an essential part of any screening process to confirm the presence of congenital anomaly as a cause of kinked tail. PMID- 27653430 TI - Impacts of urbanisation level and distance from potential natural mosquito breeding habitats on the abundance of canine dirofilariosis. AB - Dirofilariosis is an emerging mosquito-borne veterinary and medical problem in the Northern hemisphere. The ecological investigation of 56 canine dirofilariosis cases in new endemic locations was performed in Szeged, Hungary. The aim was to analyse the influence of the spatial patterns of dog abundance and the potential mosquito breeding habitats on the spatial occurrence patterns of dirofilariosis in the city of Szeged. The limnoecological characterisation was based on the fluvial habitat classification of Amoros of natural water bodies; the built environment was evaluated using the UrbanisationScore urbanisation intensity measuring software. Dirofilaria immitis accounted for 51% and D. repens for 34.3% of the dirofilariosis cases, and in 20% of the cases only the Knott's test was positive. It was concluded that most of the cases were related to locations with a medium to high urbanisation index, although the proximity of mosquito-bearing waters also played an important role in the observed spatial infection patterns. We found that the distance from potential mosquito habitats and the urbanisation intensity determine the abundance of dirofilariosis in urban environments. PMID- 27653431 TI - Multiple congenital cardiovascular defects including type IV persistent truncus arteriosus in a Shetland pony - Short communication. AB - This case report describes the pathological findings of multiple congenital cardiac defects in a 2-year-old female Shetland pony with clinical signs of chronic respiratory distress. Persistent truncus arteriosus (PTA) type IV, interventricular septal defect, overriding aorta, pulmonary trunk agenesis, pulmonary arteries arising from the descending aorta, and compensatory right ventricular hypertrophy were observed. PMID- 27653432 TI - Effect of ELISA kit manufacturing process and incubation time on progesterone concentration measured in dog serum for ovulation diagnosis - Short communication. AB - Twenty-two serum samples of healthy bitches were tested with the frozen and lyophilised version of the same ELISA kit (Quanticheck, Faculty of Veterinary Science, Budapest, Hungary). Samples were chosen on the basis of their progesterone (P4) concentrations, which were between 1.00 and 20.00 ng/mL. As it is well known, this range has the highest clinical relevance in ovulation diagnosis. Both types of microplates were read at 15-min intervals from the 15th until the 90th minute (min) of incubation, and the results were compared with those of frozen plates at 60 min of incubation as 100 percent. Lyophilised microplates gave on average 18 percent higher results than the frozen version at equal incubation times. The highest difference between lyophilised and frozen samples was observed at 45 and 60 min of incubation. Ninety-four percent of the reaction in the frozen microplate occurred in the first 15 min, and during the subsequent 30 min the reaction seemingly stopped. After the 45th min of incubation, this 94 percent increased to 108 percent in the subsequent 30 min, which remained the final approximate result at the end of the 90 min of incubation. In contrast to the frozen microplate, the measured concentration increased continuously in the lyophilised version and reached the highest level at the 60th min. The results of the lyophilised microplate reached the same level at 30 min of incubation as those of the frozen version at 60 min. In conclusion, a mechanical increase or decrease of the incubation time does not generate a linear change in the test results. This study demonstrated that the results of a series of samples collected from the same bitch cannot be compared if they are measured with different laboratory methods or different ELISA kits. PMID- 27653433 TI - Quick cytogenetic screening of breeding bulls using flow cytometric sperm DNA histogram analysis. AB - The aim of the present study was to test the FXCycle PI/RNase kit for routine DNA analyses in order to detect breeding bulls and/or insemination doses carrying cytogenetic aberrations. In a series of experiments we first established basic DNA histogram parameters of cytogenetically healthy breeding bulls by measuring the intraspecific genome size variation of three animals, then we compared the histogram profiles of bulls carrying cytogenetic defects to the baseline values. With the exception of one case the test was able to identify bulls with cytogenetic defects. Therefore, we conclude that the assay could be incorporated into the laboratory routine where flow cytometry is applied for semen quality control. PMID- 27653434 TI - Correlation of carcass meat content with development of the reproductive system in sexually immature gilts. AB - This study evaluated the correlation of carcass meat content with the development of the reproductive system in sexually immature gilts of Polish Large White (PLW) and Polish Landrace (PL) breeds. The results, obtained from three groups (I, II, III) of gilts differing in lean meat percentage, indicate an effect on fattening and slaughtering traits as well as on the morphometric characteristics of the uterus. There were statistically significant differences in the values of fattening and slaughtering traits in the groups of gilts tested. Studies on the relationship between morphometric characteristics of the reproductive system and carcass meat content showed that there was a correlation between the weight of the uterus with and without the broad ligament and the meat content of the carcass. The weight of the uterus was higher (P <= 0.05) in gilts with lower meat content. The negative influence of high gilt meatiness on development of the reproductive system was more pronounced in PLW gilts. PMID- 27653435 TI - T-2 mycotoxin slows down the development of mouse blastocysts, decreases their blastomere number and increases chromatin damage. AB - The mycotoxin T-2 has many harmful effects on mammalian cells and reproductive functions. In the present study, the in vitro effect of T-2 toxin on mouse blastocysts was examined. Embryos were cultured in media supplemented with 0.5, 0.75 and 1 ng/ml T-2. Different exposure times were applied [96 h (treatment I) or 24 h following 72 h in toxin-free media (treatment II)]. Blastomere number, nuclear chromatin status and blastocoel formation were investigated in blastocysts. Our data show that the effect of T-2 toxin may vary depending on the stage of the embryo at the start of exposure. At 96 h of exposure, the blastocysts had blastomeres with normal chromatin quality but their developmental potential was decreased. After 24 h of exposure applied following a 72-h culture, blastomeres had a higher level of chromatin damage, although their developmental potential was the same as in the control embryos. In both cases, decreased mitotic rate was found, which resulted in decreased blastomere number even at low toxin concentration. PMID- 27653436 TI - Demonstration of homologous recombination events in the evolution of bovine viral diarrhoea virus by in silico investigations. AB - Complete genome sequences of bovine viral diarrhoea virus types 1 and 2 (BVDV-1 and 2) deposited in the GenBank were submitted to bioinformatic analysis using a recombination-detecting software. The results indicate that recombination events are not rare in the case of BVDV, which frequently causes immunotolerance and, consequently, persistent infection in calves. The lack of specific immunity provides an ideal possibility for multiple infections by antigenically related but genetically different BVDV strains, and hence recombinations may occur. Among the 62 BVDV-1 genomes five recombinants and their possible parent strains, while among the 50 BVDV-2 genomes one simple recombinant and its parent strains were identified, which were supported by extremely strong probability values (P values varying between 1.26 * 10-4 and 1.58 * 10-310). Besides the newly identified recombinants, recombination events described previously were confirmed, but in some of these cases former information was completed with new data, or different parent(s) were suggested by the programme (RDP 4.46 BETA) used in this study. PMID- 27653437 TI - Primary payer status, individual patient characteristics, and hospital-level factors affecting length of stay and total cost of hospitalization in total laryngectomy. AB - BACKGROUND: Medicaid and uninsured patients anecdotally incur higher cost and length of stay because of nonmedical, discharge-related factors. The purpose of this study was to investigate the association between primary payer and length of stay and cost, controlling for comorbidities and complications, in patients undergoing total laryngectomy. METHODS: The sample included 4128 patients who underwent total laryngectomy in the 2005 to 2010 National Inpatient Sample (NIS). Patients were categorized into 4 subgroups based on payer status: Medicare, Medicaid, uninsured, and private insurance. Using multilevel modeling, we examined differences in length of stay and hospitalization costs. RESULTS: The odds of being in the top quartile of length of stay increased for Medicaid patients by 41% (odds ratio [OR] = 1.41; 95% confidence interval [CI] = 1.03 1.92) compared with privately insured patients. CONCLUSION: After controlling for medical factors, Medicaid patients had increased lengths of stay. Overall costs were highest for those with public insurance, but no difference was seen for the adjusted cost. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 311-319, 2017. PMID- 27653438 TI - Accuracy of weight loss information in Spanish search engine results on the internet. AB - OBJECTIVE: To systematically assess the quality of online information related to weight loss that Spanish speakers in the U.S. are likely to access. METHODS: This study evaluated the accessibility and quality of information for websites that were identified from weight loss queries in Spanish and compared this with previously published results in English. The content was scored with respect to five dimensions: nutrition, physical activity, behavior, pharmacotherapy, and surgical recommendations. RESULTS: Sixty-six websites met eligibility criteria (21 commercial, 24 news/media, 10 blogs, 0 medical/government/university, 11 unclassified sites). Of 16 possible points, mean content quality score was 3.4 (SD = 2.0). Approximately 1.5% of sites scored greater than 8 (out of 12) on nutrition, physical activity, and behavior. Unsubstantiated claims were made on 94% of the websites. Content quality scores varied significantly by type of website (P < 0.0001) with unclassified websites scoring the highest (mean = 6.3, SD = 1.4) and blogs scoring the lowest (mean = 2.2, SD = 1.2). All content quality scores were lower for Spanish websites relative to English websites. CONCLUSIONS: Weight loss information accessed in Spanish Web searches is suboptimal and relatively worse than weight loss information accessed in English, suggesting that U.S. Spanish speakers accessing weight loss information online may be provided with incomplete and inaccurate information. PMID- 27653440 TI - Raman Spectroscopy for the Endoscopic Diagnosis of Esophageal, Gastric, and Colonic Diseases. AB - Globally white-light endoscopy with biopsy sampling is the gold standard diagnostic modality for esophageal, gastric, and colonic pathologies. However, there is overwhelming evidence to highlight the deficiencies of an approach based predominantly on eyeball visualization. Biopsy sampling is also problematic due in part to excessive sampling and hence attendant cost. Various innovations are currently taking place in the endoscopic domain to aid operators in diagnosis forming. These include narrow band imaging which aims to enhance the surface anatomy and vasculature, and confocal laser endomicroscopy which provides real time histological information. However, both of these tools are limited by the skill of the operator and the extensive learning curve associated with their use. There is a gap therefore for a new form of technology that relies solely on an objective measure of disease and reduces the need for biopsy sampling. Raman spectroscopy (RS) is a potential platform that aims to satisfy these criteria. It enables a fingerprint capture of tissue in relation to the protein, DNA, and lipid content. This focused review highlights the strong potential for the use of RS during endoscopic gastroenterological examination. PMID- 27653439 TI - Perineural and intraneural cutaneous granulomas in granulomatous mycosis fungoides mimicking tuberculoid leprosy. AB - BACKGROUND: Histological similarities between granulomas and granulomatous mycosis fungoides (GMF) may lead to misdiagnoses of sarcoidosis or leprosy. METHODS: This report presents four patients with GMF in whom skin biopsies showed perineural and intraneural granulomas that were confused with tuberculoid leprosy granulomas. RESULTS: Patient 1 presented with erythematous plaques and bulky nodules. Biopsy findings suggested cutaneous sarcoidosis. Tumor resection showed granulomatous infiltrate extending to the fascia and skeletal muscle. Clinicopathological correlations permitted a diagnosis of GMF. Patient 2 presented with erythematous plaques. Skin biopsies had indicated sarcoidosis. Resection of a thigh nodule excluded leprosy, and GMF was diagnosed. Patient 3 presented with scaly, hyperpigmented plaques. Biopsy showed diffuse granulomatous inflammation with epithelioid and giant cells, abundant lymphocytes, and some eosinophils, and indicated GMF. Patient 4 presented with pruritic, erythematous plaques. Biopsy of an indurated mammary plaque initially indicated sarcoid granulomatous inflammation. Biopsy review suggested GMF. CONCLUSIONS: This study highlights both the diagnosis of GMF, and granulomatous cutaneous nerve injury in GMF and its possible confusion with leprosy granulomas. The histological diagnosis of GMF includes: (i) a granulomatous infiltrate rich in giant cells, emperipolesis, histiocytic cells, and scattered eosinophils, which may reach the fascia and muscle; (ii) the absence of elastic fibers or their phagocytosis by giant cells; and (iii) lymphocytes that may show atypia and epidermotropism. Deep biopsies reveal GMF diagnostic changes and, in conjunction with clinicopathological correlations, exclude a diagnosis of leprosy and support one of GMF, thus facilitating its appropriate management. PMID- 27653441 TI - Colon Capsule Endoscopy: Where Are We and Where Are We Going. AB - Colon capsule endoscopy (CCE) is a noninvasive technique for diagnostic imaging of the colon. It does not require air inflation or sedation and allows minimally invasive and painless colonic evaluation. The role of CCE is rapidly evolving; for example, for colorectal screening (colorectal cancer [CRC]) in average-risk patients, in patients with an incomplete colonoscopy, in patients refusing a conventional colonoscopy, and in patients with contraindications for conventional colonoscopy. In this paper, we comprehensively review the technical characteristics and procedure of CCE and compare CCE with conventional methods such as conventional colonoscopy or computed tomographic colonography. Future expansion of CCE in the area of CRC screening for the surveillance of polyps and adenomatous lesions and for assessment of inflammatory bowel disease is also discussed. PMID- 27653442 TI - Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP. AB - The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C-terminal "follower" sequence, rather than the canonical N-terminal "leader" sequence. We report herein the structural and biochemical characterization of BotP, a leucyl aminopeptidase-like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro- mycin. PMID- 27653443 TI - Is universal antifungal prophylaxis mandatory in adults after lung transplantation? A review and meta-analysis of observational studies. AB - BACKGROUND: Lung transplant (LTX) recipients are at high risk of invasive Aspergillus infections (IAI). However, no randomized-controlled trials (RCT) or international guidelines on antifungal prophylaxis (AFP) in the LTX population exist. METHODS: A meta-analysis was performed to determine whether AFP reduces the rate of IAI after LTX. A total of six eligible observational studies (five with no prophylaxis, one with targeted prophylaxis, three studies including heart/lung transplantation) with a total of 748 patients were included. RESULTS: The pooled odds ratio (OR) for IAI (62 IFI in the intervention arm and 82 in the control group) was 0.234 (95% confidence interval [CI] 0.097-0.564, P=0.001, z= 3.237). Pooled studies were characterized by substantial heterogeneity (I2 =66.64%); number needed to treat was 6.8. A subgroup analyses with exclusion of heart transplant recipients also showed a statistically significant reduction in IAI with AFP (OR 0.183, 95% CI 0.0449-0.744, P=0.018). CONCLUSION: This study suggests that universal antifungal prophylaxes reduces incidence of IAI after LTX. However, included studies are limited by small sample size, single-center structure without randomization, mixed population (including heart/heart-lung transplant), and heterogeneity due to variations in immunosuppression, type, and duration of AFP. Therefore, there is a clear need for an adequately powered RCT. PMID- 27653444 TI - Standard-dose versus low-dose azathioprine in the treatment of Crohn's disease: A prospective randomized study. AB - OBJECTIVE: Azathioprine (AZA) is widely used to treat Crohn's disease (CD) with a recommended dose of 2-2.5 mg/kg per day for Westerners. Asian patients are suggested to take a lower dose. However, many clinicians reported poor efficacy with a reduced dose. This study aimed to explore a efficient and safe dose of AZA providing the best efficacy for Chinese CD patients. METHODS: Fifty patients with active CD were enrolled and randomized into two groups (n = 25 each). All other treatments were the same except that group A received 1 mg/kg per day and group B took 2 mg/kg per day of AZA. Complete remission (CR) rate and response rate at weeks 12, 24 and 48 were assessed by using intent-to-treat (ITT) and per-protocol (PP) analyses. Adverse events and recurrence rate were also evaluated. RESULTS: At week 48, CR rate and response rate in group B (ITT: 50.0% and 59.1%; PP: 57.9% and 68.4%) were significantly higher than those in group A (ITT: 13.0% and 17.4%; PP: 16.7% and 22.2%) (P < 0.05). Nine adverse events occurred, including pancreatitis (n = 1), arthritis (n = 2) and myelosuppression (n = 6). There was no significant difference in adverse events between the two groups. However, recurrence rate was significantly higher in group A than in group B (P = 0.042). CONCLUSION: AZA 2 mg/kg per day is more appropriate than 1 mg/kg per day for Chinese CD patients with a high efficacy, a low recurrence rate and not increased adverse events. PMID- 27653446 TI - A reporting system for endometrial cytology: Cytomorphologic criteria-Implied risk of malignancy. AB - BACKGROUND: There have been various attempts to assess endometrial lesions on cytological material obtained via direct endometrial sampling. The majority of efforts focus on the description of cytological criteria that lead to classification systems resembling histological reporting formats. These systems have low reproducibility, especially in cases of atypical hyperplasia and well differentiated carcinomas. Moreover, they are not linked to the implied risk of malignancy. METHODS: The material was collected from women examined at the outpatient department of four participating hospitals. We analyzed 866 consecutive, histologically confirmed cases. The sample collection was performed using the EndoGyn device, and processed via Liquid Based Cytology, namely ThinPrep technique. The diagnostic categories and criteria were established by two cytopathologists experienced in endometrial cytology; performance of the proposed reporting format was assessed on the basis of histological outcome; moreover, the implied risk of malignancy was calculated. RESULTS: The proposed six diagnostic categories are as follows: (i) nondiagnostic or unsatisfactory; (ii) without evidence of hyperplasia or malignancy; (iii) atypical cells of endometrium of undetermined significance; (iv) atypical cells of endometrium of low probability for malignancy; (v) atypical cells of endometrium of high probability for malignancy; and (vi) malignant. The risk of malignancy was 1.42% +/- 0.98%, 44.44% +/- 32.46% (nine cases), 4.30% +/- 4.12%, 89.80% +/- 8.47%, and 97.81% +/- 2.45%, respectively. CONCLUSION: We propose a clinically oriented classification scheme consisting of diagnostic categories with well determined criteria. Each diagnostic category is linked with an implied risk of malignancy; thus, clinicians may decide on patient management and eventually reduce unnecessary interventional diagnostic procedures. Diagn. Cytopathol. 2016;44:888 901. (c) 2016 Wiley Periodicals, Inc. PMID- 27653445 TI - A Case of Cutaneous Inflammatory Myofibroblastic Tumor. AB - Inflammatory myofibroblastic tumor (IMT) rarely occurs as a primary cutaneous lesion. We report a case of cutaneous IMT in an 8-year-old girl presenting with an ulcerated nodule on the cheek. Although cutaneous IMT poses a diagnostic challenge because of its rarity, excision of the lesion is likely to be curative. PMID- 27653447 TI - Heart failure outcomes in clinical trials of glucose-lowering agents in patients with diabetes. AB - Diabetes is a major risk factor for heart failure (HF). Patients with diabetes have a high incidence of both clinical HF and subclinical LV dysfunction. Although intensive glucose lowering does not appear to impact on HF outcomes, the choice of glucose-lowering agents plays an important role in the development of HF and related cardiovascular outcomes. Whilst metformin and insulin appear to have little impact on HF progression, the role of sulphonylurea agents in this patient population remains uncertain. Thiazolidinediones (TZDs) are associated with a significant risk of HF progression and are best avoided in patients at risk. The incretin-based therapies (GLP agonists and DPP-4 inhibitors) are generally not associated with any HF interaction. However, a small increase in HF admissions was observed with the DPP-4 inhibitor saxagliptin. The GLP-1 agonist liraglutide was recently shown to reduce cardiovascular and all-cause mortality, yet hospitalization for HF was not significantly reduced. The SGLT2 inhibitor empagliflozin was shown to reduce HF admissions and cardiovascular mortality in patients with prior cardiovascular disease including HF. These recent data showing improved outcomes with a glucose-lowering category provide a novel strategy to improve survival and reduce morbidity in diabetic patients at high cardiovascular disease risk. PMID- 27653448 TI - Efficacy and safety of abobotulinumtoxinA liquid formulation in cervical dystonia: A randomized-controlled trial. AB - BACKGROUND: Approved botulinum toxin A products require reconstitution. AbobotulinumtoxinA solution for injection is a ready-to-use liquid formulation of abobotulinumtoxinA. OBJECTIVES: The objective of this study was to demonstrate the superior efficacy of abobotulinumtoxinA solution for injection to placebo and to test the noninferior efficacy of abobotulinumtoxinA solution for injection versus abobotulinumtoxinA (dry formulation) in cervical dystonia. METHODS: This was a phase-3, multicenter, prospective, double-blind, randomized, active, and placebo-controlled study (N = 369). Patients with cervical dystonia were randomized (3:3:1) to abobotulinumtoxinA solution for injection 500 U, abobotulinumtoxinA 500 U, or placebo. Following the double-blind phase, patients received abobotulinumtoxinA solution for injection, open-label, for up to 4 cycles. The primary outcome was change from baseline at week 4 of the Toronto Western Spasmodic Torticollis Rating Scale total score. Secondary measures included change from baseline or cycle baseline in Toronto Western Spasmodic Torticollis Rating Scale scores. RESULTS: At week 4, both products were superior to placebo (Toronto Western Spasmodic Torticollis Rating Scale total score least square mean decrease from baseline, abobotulinumtoxinA solution for injection 500 U -12.5, abobotulinumtoxinA 500 U -14.0, placebo -3.9; P < .0001 vs placebo). The noninferiority limit of 3 points in the Toronto Western Spasmodic Torticollis Rating Scale total score at week 4 was not met for abobotulinumtoxinA solution for injection versus abobotulinumtoxinA. Toronto Western Spasmodic Torticollis Rating Scale total score reductions were maintained for up to 4 cycles of abobotulinumtoxinA solution for injection open-label follow-up treatment. Safety profiles of abobotulinumtoxinA solution for injection and abobotulinumtoxinA were similar, with dysphagia and injection-site pain the most frequent drug-related adverse events. CONCLUSIONS: Although the predefined noninferiority criterion was not met, abobotulinumtoxinA solution for injection was similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale total scores with a similar safety profile. AbobotulinumtoxinA solution for injection efficacy was maintained with chronic open-label treatment, and this novel formulation may add convenience as well as dosing accuracy to treatment with abobotulinumtoxinA. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27653449 TI - Do metabolic derangements in end-stage polycystic kidney disease differ versus other primary kidney diseases? AB - AIM: Autosomal dominant polycystic kidney disease (ADPKD), a systemic disorder caused by mutation in genes encoding polycystins, has been reported to lead to metabolic derangements including new-onset diabetes mellitus after kidney transplantation. We analyzed markers of insulin resistance (IR), inflammation, nutritional status and insulin-like growth factor-1 (IGF-1) in end-stage renal disease (ESRD) patients with ADPKD and ESRD patients with other primary kidney diseases. METHODS: In a post hoc cross-sectional analysis in 254 non-diabetic CKD 5 patients starting on dialysis, glucose metabolism (insulin, IGF-1, homeostasis model assessment of IR, HOMA-IR), inflammation (high sensitivity C-reactive protein, interleukin-6, and tumour necrosis factor), nutritional status, and bone mineral density (BMD), were assessed. Survival was recorded for median time of 28 months (IQR 15-48 months). RESULTS: Neither indices of IR, nor IGF-1, inflammatory status, nutritional status, or BMD were different in patients with ADPKD as compared to other aetiologies of ESRD. Kaplan-Meier curves showed better survival among the ADPKD group versus other aetiologies, even after an exclusion of diabetic patients. CONCLUSIONS: The ESRD phenotype did not differ in ADPKD versus other primary kidney diseases in terms of markers of IR, inflammation, and nutritional status. This argues against the proposition that ADPKD patients are more prone to develop metabolic derangements beyond those generally observed in advanced CKD. However, additional studies are warranted to further elucidate systemic metabolic aspects of ADPKD. PMID- 27653450 TI - Feasibility, appropriateness, meaningfulness and effectiveness of patient participation at bedside shift reporting: mixed-method research protocol. AB - AIM: To evaluate the feasibility, appropriateness, meaningfulness and effectiveness of bedside shift reporting in a minimum of five interventions and five control wards. BACKGROUND: Hospitals continually improve their quality of care. Next to improvements in clinical performance, more patient participation is stimulated through different methods. Methods to enhance patient participation such as bedside shift reporting lack rigorously performed research to determine their feasibility, appropriateness, meaningfulness and effectiveness. Small-scale research and a previous pilot study indicate that bedside shift reporting improves patient participation, nurse-nurse communication and nurse-patient communication. DESIGN: The development, implementation and evaluation of bedside shift report are based on the Medical Research Council framework for complex interventions in health care. A matched, controlled, mixed-method, longitudinal study design will be used. The Feasibility-Appropriateness-Meaningfulness Effectiveness framework will be applied for the quantitative and qualitative evaluation of bedside shift report. METHODS: A tailored intervention and implementation process for bedside shift report will be developed using diagnostic interviews, co-design and acceptability testing. The intervention will be evaluated before implementation and three times after implementation. Individual and focus group interviews will be performed. Questionnaires, observations and analysis of the medical records and administrative databases will be completed. This study was funded in October 2015. Research Ethics Committee approval was granted in March 2016. DISCUSSION: There is a pressing need for rigorous research into the effects of interventions for improving patient participation. This study addresses the significance of bedside shift report as an intervention to improve quality of care, communication and patient participation within a large-scale, matched, controlled research design. PMID- 27653451 TI - Beneficial effects of moderate alcohol use-a case for Occam's razor? PMID- 27653452 TI - Micropipette Technique Study of Natural and Synthetic Lung Surfactants at the Air Water Interface: Presence of a SP-B Analog Peptide Promotes Membrane Aggregation, Formation of Tightly Stacked Lamellae, and Growth of Myelin Figures. AB - The present study is a microscopic interfacial characterization of a series of lung surfactant materials performed with the micropipette technique. The advantages of this technique include the measurement of equilibrium and dynamic surface tensions while acquiring structural and dynamic information at microscopic air-water interfaces in real time and upon compression. Here, we characterized a series of animal-derived and synthetic lung surfactant formulations, including native surfactant obtained from porcine lungs (NS); the commercial Curosurf, Infasurf, and Survanta; and a synthetic Super Mini-B (SMB) containing formulation. It was observed that the presence of the natural hydrophobic proteins and, more strikingly, the peptide SMB, promoted vesicle condensation as thick membrane stacks beneath the interface. Only in the presence of SMB, these stacks underwent spontaneous structural transformations, consisting of the nucleation and growth of microtubes and in some cases their subsequent coiling into helices. The dimensions of these tubes (2-15 MUm diameter) and their linear (2-3 MUm/s) and volumetric growth rates (20-30 MUm3/s) were quantified, and no specific effects were found on them for increasing SMB concentrations from 0.1 to 4%. Nevertheless, a direct correlation between the number of tubes and SMB contents was found, suggesting that SMB molecules are the promoters of tube nucleation in these membranes. A detailed analysis of the tube formation process was performed following previous models for the growth of myelin figures, proposing a combined mechanism between dehydration-rehydration of the lipid bilayers and induction of mechanical defects by SMB that would act as nucleation sites for the tubes. The formation of tubes was also observed in Infasurf, and in NS only after subsequent expansion and compression but neither in the other clinical surfactants nor in protein-free preparations. Finally, the connection between this data and the observations from the lung surfactant literature concerning the widely reported "near-zero surface tension" for lung surfactant films and intact alveolar surfaces is also discussed. PMID- 27653453 TI - Accuracy of a low-cost global positioning system receiver for estimating grade during outdoor walking. AB - The aim of this study was to assess, for the first time, the accuracy of a low cost global positioning system (GPS) receiver for estimating grade during outdoor walking. Thirty subjects completed outdoor walks (2.0, 3.5 and 5.0 km . h-1) in three randomized conditions: 1/level walking on a 0.0% grade; 2/graded (uphill and downhill) walking on a 3.4% grade; and 3/on a 10.4% grade. Subjects were equipped with a GPS receiver (DG100, GlobalSat Technology Corp., Taiwan; ~US$75). The GPS receiver was set to record at 1 Hz and its antenna was placed on the right shoulder. Grade was calculated from GPS speed and altitude data (grade = altitude variation/travelled distance * 100). Two methods were used for the grade calculation: one using uncorrected altitude data given by the GPS receiver and another one using corrected altitude data obtained using map projection software (CartoExploreur, version 3.11.0, build 2.6.6.22, Bayo Ltd, Appoigny, France, ~US$35). Linear regression of GPS-estimated versus actual grade with R 2 coefficients, bias with 95% limits of agreement (+/-95% LoA), and typical error of the estimate with 95% confidence interval (TEE (95% CI)) were computed to assess the accuracy of the GPS receiver. 444 walking periods were performed. Using uncorrected altitude data, we obtained: R 2 = 0.88 (p < 0.001), bias = 0.0 +/- 6.6%, TEE between 1.9 (1.7-2.2)% and 4.2 (3.6-4.9)% according to the grade level. Using corrected altitude data, we obtained: R 2 = 0.98 (p < 0.001), bias = 0.2 +/- 1.9%, TEE between 0.2 (0.2-0.3)% and 1.0 (0.9-1.2)% according to the grade level. The low-cost GPS receiver used was weakly accurate for estimating grade during outdoor walking when using uncorrected altitude data. However, the accuracy was greatly improved when using corrected altitude data. This study supports the potential interest of using GPS for estimating energy expenditure during outdoor walking. PMID- 27653454 TI - Synthesis and fungicidal activity of tryptophan analogues - the unexpected calycanthaceous alkaloid derivatives. AB - A series of 21 N-protected tryptophan derivatives were synthesised from tryptophan in good yields. Their structures were characterised by IR, 1H NMR, 13C NMR, DEPT (90 degrees and 135 degrees ) and MS analysis. The synthesised compounds were evaluated against a wide variety of plant pathogen fungi. Compounds a19 and a21 displayed activity against Fusarium oxysporum (F. oxysporum), and compound a21 showed high activity against F. oxysporum and Eggplant Verticillium, with EC50 values of 58.27 and 77.39 MUg mL-1, respectively. Considering that the bioassay of the title compounds was evaluated, effects of the chain alkyl substituents may contribute to the significant variations in fungicidal potency. Their structure-antifungal activity relationships were also discussed. These results will pave the way for further design, structural modification and development of calycanthaceous alkaloids as antimicrobial agents. PMID- 27653455 TI - Strategies to develop vaccines of pediatric interest. AB - INTRODUCTION: The success of the vaccines available on the market has significantly increased interest in vaccine development. Areas covered: The main aim of this paper is to discuss the most important vaccines of pediatric interest that are currently being developed. New pneumococcal vaccines and vaccines against group B Streptococcus, Staphylococcus aureus and respiratory syncytial virus are analyzed in detail. Expert commentary: Advances in understanding human immunology, including human monoclonal antibody identification, sequencing technology, and the ability to solve atomic level structures of vaccine targets have provided tools to guide the rational design of future vaccines. It is likely that some of these vaccines will reach the market in the future and will thus partially contribute to the prevention of very severe diseases that significantly affect the morbidity and mortality of children. However, further studies in animals and several clinical trials in children must be performed before new vaccines become licensed. PMID- 27653456 TI - Systematic analysis of genetic variants in Han Chinese patients with sporadic Parkinson's disease. AB - Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Accumulated evidence confirms that genetic factors play a considerable role in PD pathogenesis. To examine whether point variants or haplotypes are associated with PD development, genotyping of 35 variants in 22 PD-related genes was performed in a well-characterized cohort of 512 Han Chinese PD patients and 512 normal controls. Both Pearson's chi2 test and haplotype analysis were used to evaluate whether variants or their haplotypes were associated with PD in this cohort. The only statistically significant differences in genotypic and allelic frequencies between the patients and the controls were in the DnaJ heat shock protein family (Hsp40) member C10 gene (DNAJC10) variant rs13414223 (P = 0.004 and 0.002, respectively; odds ratio = 0.652, 95% confidence interval: 0.496-0.857). No other variants or haplotypes exhibited any significant differences between these two groups (all corrected P > 0.05). Our findings indicate that the variant rs13414223 in the DNAJC10 gene, a paralog of PD-related genes DNAJC6 and DNAJC13, may play a protective role in PD. This suggests it may be a PD-associated gene. PMID- 27653457 TI - Polycyclic Eruption of the Thighs. PMID- 27653458 TI - Violation of the transit-time limit toward generation of ultrashort electron bunches with controlled velocity chirp. AB - Various methods to generate ultrashort electron bunches for the ultrafast science evolved from the simple configuration of two-plate vacuum diodes to advanced technologies such as nanotips or photocathodes excited by femtosecond lasers. In a diode either in vacuum or of solid-state, the transit-time limit originating from finite electron mobility has caused spatiotemporal bunch-collapse in ultrafast regime. Here, we show for the first time that abrupt exclusion of transit-phase is a more fundamental origin of the bunch-collapse than the transit time limit. We found that by significantly extending the cathode-anode gap distance, thereby violating the transit-time limit, the conventional transit-time related upper frequency barrier in diodes can be removed. Furthermore, we reveal how to control the velocity chirp of bunches leading to ballistic bunch compression. Demonstration of 0.707 THz-, 46.4 femtosecond-bunches from a 50 MUm wide diode in three-dimensional particle-in-cell simulations shows a way toward simple and compact sources of ultrafast electron bunches for diverse ultrafast sciences. PMID- 27653459 TI - Corrigendum: Staircase Quantum Dots Configuration in Nanowires for Optimized Thermoelectric Power. PMID- 27653460 TI - Bioelectronic interfaces by spontaneously organized peptides on 2D atomic single layer materials. AB - Self-assembly of biological molecules on solid materials is central to the "bottom-up" approach to directly integrate biology with electronics. Inspired by biology, exquisite biomolecular nanoarchitectures have been formed on solid surfaces. We demonstrate that a combinatorially-selected dodecapeptide and its variants self-assemble into peptide nanowires on two-dimensional nanosheets, single-layer graphene and MoS2. The abrupt boundaries of nanowires create electronic junctions via spatial biomolecular doping of graphene and manifest themselves as a self-assembled electronic network. Furthermore, designed peptides form nanowires on single-layer MoS2 modifying both its electric conductivity and photoluminescence. The biomolecular doping of nanosheets defined by peptide nanostructures may represent the crucial first step in integrating biology with nano-electronics towards realizing fully self-assembled bionanoelectronic devices. PMID- 27653461 TI - Thoracic wall reconstruction with bioabsorbable plates in pediatric malignant thoracic wall tumors. AB - AIM: Childhood malignant chest wall tumors may require extensive surgical resection and reconstruction with musculoskeletal flaps or non-resorbable prosthetic materials. Implant-related complications and scoliosis often occur. This study analyzes the outcomes of chest wall reconstruction using resorbable plates as an alternative approach. METHODS: Retrospective review (2007-2015) of patients who underwent resection of malignant primary chest wall tumors in 2 tertiary pediatric centers. Reconstruction was performed using copolymer (l lactic and glycolic acid) plates, fixed to the ribs and surrounding structures with copolymer screws and/or polyglactin sutures. RESULTS: Eight patients aged 10.6+2.6years were treated. There were no operative complications, and implant removal was not required in any case. Six patients received postoperative radiotherapy. Over follow-up (39.6months, range 9.4-78), chest wall shape was maintained in all, and there were no radiological artifacts. Three patients developed scoliosis (Cobb 17 degrees -33 degrees ), but treatment was needed only in one, who had undergone hemivertebrectomy. There were no cases of local tumor relapse. One patient died because of metastatic spread. CONCLUSIONS: Implantation of bioabsorbable l-lactic and glycolic acid copolymer plates with a relatively simple technique provided a rigid, stable reconstruction with only mild mid-/long term complications. Resorbable plates may be a good alternative for pediatric chest wall reconstruction. LEVEL OF EVIDENCE: IV. PMID- 27653462 TI - Metabolic switches during the first steps of adipogenic stem cells differentiation. AB - The understanding of metabolism during cell proliferation and commitment provides a greater insight into the basic biology of cells, allowing future applications. Here we evaluated the energy and oxidative changes during the early adipogenic differentiation of human adipose tissue-derived stromal cells (hASCs). hASCs were maintained under differentiation conditions during 3 and 7days. Oxygen consumption, mitochondrial mass and membrane potential, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) and catalase activities, non-protein thiols (NPT) concentration and lipid peroxidation were analyzed. We observed that 7days of adipogenic induction are required to stimulate cells to consume more oxygen and increase mitochondrial activity, indicating organelle maturation and a transition from glycolytic to oxidative energy metabolism. ROS production was only increased after 3days and may be involved in the differentiation commitment. ROS source was not only the mitochondria and we suggest that NOX proteins are related to ROS generation and therefore adipogenic commitment. ROS production did not change after 7days, but an increased activity of catalase and NPT concentration as well as a decreased lipid peroxidation were observed. Thus, a short period of differentiation induction is able to change the energetic and oxidative metabolic profile of hASCs and stimulate cytoprotection processes. PMID- 27653463 TI - Urinary dopamine in psychotic disorders is similar to that of pheochromocytoma and paraganglioma. PMID- 27653465 TI - Hollow manganese oxide nanoparticle-enhanced MRI of hypoxic-ischaemic brain injury in the neonatal rat. AB - OBJECTIVE: To determine the utility of hollow manganese oxide nanoparticle (HMON) enhanced MRI in depicting and monitoring apoptotic area following hypoxic ischaemic injury in a neonatal rat brain and to evaluate the longitudinal evolution of hypoxic-ischaemic brain injury (HII) up to 21 days. METHODS: The institutional animal care and use committee approval was obtained. The Rice Vannucci model of HII was used in 7-day-old rat pups (n = 17). MRI was performed 1, 3, 7, 14 and 21 days after HII with intraperitoneal injection of HMON. Relative contrast values in the injured hemisphere and mean apparent diffusion coefficient values were calculated at each time point. Apoptosis and reactive astrogliosis were detected by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labelling (TUNEL) and glial fibrillary acidic protein staining, and the distribution and intensity of immunohistochemical staining were directly compared with those of HMON enhancement on MRI. RESULTS: The dorsolateral thalamus, hippocampus and remaining cortex of the injured hemisphere showed HMON enhancement from 3 to 21 days after HII. The mean relative contrast values in the dorsolateral thalamus showed an increase from a negative value at 1 day to 16.5 +/- 4.8% at 21 days. The apoptotic cells and reactive astrocytes were observed on immunohistochemical staining from 1 to 21 days after HII. The accumulation of apoptotic cells regionally matched with the areas of HMON enhancement, while that of reactive astrocytes did not. CONCLUSION: The areas of HMON enhancement showed best spatial agreement with those of apoptosis on TUNEL staining. Both HMON enhancement and TUNEL-positive cells were observed up to 21 days after HII. Advances in knowledge: The strength of our study is the visualization of apoptotic area in vivo using HMON-enhanced MRI, and we also showed that HII has a prolonged evolution lasting for several weeks. PMID- 27653464 TI - Comparative genomics reveals adaptive evolution of Asian tapeworm in switching to a new intermediate host. AB - Taenia saginata, Taenia solium and Taenia asiatica (beef, pork and Asian tapeworms, respectively) are parasitic flatworms of major public health and food safety importance. Among them, T. asiatica is a newly recognized species that split from T. saginata via an intermediate host switch ~1.14 Myr ago. Here we report the 169- and 168-Mb draft genomes of T. saginata and T. asiatica. Comparative analysis reveals that high rates of gene duplications and functional diversifications might have partially driven the divergence between T. asiatica and T. saginata. We observe accelerated evolutionary rates, adaptive evolutions in homeostasis regulation, tegument maintenance and lipid uptakes, and differential/specialized gene family expansions in T. asiatica that may favour its hepatotropism in the new intermediate host. We also identify potential targets for developing diagnostic or intervention tools against human tapeworms. These data provide new insights into the evolution of Taenia parasites, particularly the recent speciation of T. asiatica. PMID- 27653467 TI - Disentangling the ACA's Coverage Effects - Lessons for Policymakers. PMID- 27653466 TI - Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke. AB - Somatic cells can be directly converted into induced neural stem cells (iNSCs) by defined transcription factors. However, the therapeutic effect of undifferentiated iNSCs on ischemic stroke has not been demonstrated. In this study, we used a mouse model of transient middle cerebral artery occlusion (tMCAO). iNSCs (5 * 105) were injected directly into the ipsilateral striatum and cortex 24 h after tMCAO. Histological analysis was performed at 7 days, 28 days, and 8 months after tMCAO. We found that iNSC transplantation successfully improved the survival rate of stroke model mice with significant functional recovery from the stroke. The fate of engrafted iNSCs was that the majority of iNSCs had differentiated into astroglial cells but not into neural cells in both the sham-operated brain and the poststroke brain without forming a tumor up to 8 months after tMCAO. Our data suggest that the directly converted iNSCs can be regarded as a candidate of safe cell resource for transplantation therapy in patients suffering from ischemic stroke. PMID- 27653468 TI - Continuous venovenous hemofiltration combined with hemoperfusion for toxic epidermal necrolysis: a retrospective cohort study. AB - AIM: The current treatments of toxic epidermal necrolysis (TEN) are limited to the discontinuation of a suspect medication and supportive measures. We conducted a retrospective study to evaluate the efficacy of adding continuous venovenous hemofiltration (CVVH) and hemoperfusion (HP) to the conventional treatment for TEN. METHODS: TEN patients who were admitted to our center between January 2008 and May 2016 were considered as candidates. The included patients were divided into the CVVH&HP group (n = 34) and the conventional group (n = 34) according to their accepted therapies during hospital stay. RESULTS: The patients in the conventional group had a significantly reduced 28-day survival proportion compared with patients in the CVVH&HP group (73.5 versus 91.2%, p = .047). The adjusted results demonstrated that the conventional group had a significantly higher risk of 28-day mortality as well. Moreover, patients in the CVVH&HP group were associated with significantly shorter hospital stay, rash, fever, and antibiotic durations. However, the addition of CVVH&HP to conventional treatment did not significantly increase the in-hospital cost. CONCLUSIONS: In conclusion, CVVH&HP might be a safe and effective adjuvant therapy for TEN. Further well designed studies are warranted to obtain robust evidence. PMID- 27653469 TI - Developing particle emission inventories using remote sensing (PEIRS). AB - : Information regarding the magnitude and distribution of PM2.5 emissions is crucial in establishing effective PM regulations and assessing the associated risk to human health and the ecosystem. At present, emission data is obtained from measured or estimated emission factors of various source types. Collecting such information for every known source is costly and time-consuming. For this reason, emission inventories are reported periodically and unknown or smaller sources are often omitted or aggregated at large spatial scale. To address these limitations, we have developed and evaluated a novel method that uses remote sensing data to construct spatially resolved emission inventories for PM2.5. This approach enables us to account for all sources within a fixed area, which renders source classification unnecessary. We applied this method to predict emissions in the northeastern United States during the period 2002-2013 using high-resolution 1 km * 1 km aerosol optical depth (AOD). Emission estimates moderately agreed with the EPA National Emission Inventory (R2 = 0.66-0.71, CV = 17.7-20%). Predicted emissions are found to correlate with land use parameters, suggesting that our method can capture emissions from land-use-related sources. In addition, we distinguished small-scale intra-urban variation in emissions reflecting distribution of metropolitan sources. In essence, this study demonstrates the great potential of remote sensing data to predict particle source emissions cost effectively. IMPLICATIONS: We present a novel method, particle emission inventories using remote sensing (PEIRS), using remote sensing data to construct spatially resolved PM2.5 emission inventories. Both primary emissions and secondary formations are captured and predicted at a high spatial resolution of 1 km * 1 km. Using PEIRS, large and comprehensive data sets can be generated cost effectively and can inform development of air quality regulations. PMID- 27653471 TI - Identifying N-Glycan Biomarkers in Colorectal Cancer by Mass Spectrometry. AB - Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Delineating biological markers (biomarkers) for early detection, when treatment is most effective, is key to prevention and long-term survival of patients. Development of reliable biomarkers requires an increased understanding of the CRC biology and the underlying molecular and cellular mechanisms of the disease. With recent advances in new technologies and approaches, tremendous efforts have been put in proteomics and genomics fields to deliver detailed analysis of the two major biomolecules, genes and proteins, to gain a more complete understanding of cellular systems at both genomic and proteomic levels, allowing a mechanistic understanding of the human diseases, including cancer, and opening avenues for identification of novel gene and protein based prognostic and therapeutic markers. Although the importance of glycosylation in modulating protein function has long been appreciated, glycan analysis has been complicated by the diversity of the glycan structures and the large number of potential glycosylation combinations. Driven by recent technological advances, LC-MS/MS based glycomics is gaining momentum in cancer research and holds considerable potential to deliver new glycan-based markers. In our laboratory, we investigated alterations in N-glycosylation associated with CRC malignancy in a panel of CRC cell lines and CRC patient tissues. In an initial study, LC-MS/MS-based N-glycomics were utilized to map the N-glycome landscape associated with a panel of CRC cell lines (LIM1215, LIM1899, and LIM2405). These studies were subsequently extended to paired tumor and nontumorigenic CRC tissues to validate the findings in the cell line. Our studies in both CRC cell lines and tissues identified a strong representation of high mannose and alpha2,6-linked sialylated complex N-glycans, which corroborate findings from previous studies in CRC and other cancers. In addition, certain unique glycan determinants such as bisecting beta1,4 GlcNAcylation and alpha2,3-sialylation, identified in the metastatic (LIM1215) and aggressive (LIM2405) CRC cell lines, respectively, were shown to be associated with epidermal growth factor receptor (EGFR) expression status. In this Account, we will describe the mass spectrometry based N-glycomics approach utilized in our laboratory to accurately profile the cell- and tissue-specific N glycomes associated with CRC. We will highlight altered N-glycosylation observed by our studies, consistent with findings from other cancer studies, and discuss how the observed alterations can provide insights into CRC pathogenesis, opening new avenues to identify novel disease-associated glycan markers. PMID- 27653470 TI - Bioactivity of Ruta graveolens and Satureja montana Essential Oils on Solanum tuberosum Hairy Roots and Solanum tuberosum Hairy Roots with Meloidogyne chitwoodi Co-cultures. AB - As a nematotoxics screening biotechnological system, Solanum tuberosum hairy roots (StHR) and S. tuberosum hairy roots with Meloidogyne chitwoodi co-cultures (StHR/CRKN) were evaluated, with and without the addition of the essential oils (EOs) of Satureja montana and Ruta graveolens. EOs nematotoxic and phytotoxic effects were followed weekly by evaluating nematode population density in the co cultures as well as growth and volatile profiles of both in vitro cultures types. Growth, measured by the dissimilation method and by fresh and dry weight determination, was inhibited after EO addition. Nematode population increased in control cultures, while in EO-added cultures numbers were kept stable. In addition to each of the EOs main components, and in vitro cultures constitutive volatiles, new volatiles were detected by gas chromatography and gas chromatography coupled to mass spectrometry in both culture types. StHR with CRKN co-cultures showed to be suitable for preliminary assessment of nematotoxic EOs. PMID- 27653472 TI - Angling for A Better View. PMID- 27653473 TI - Microfluidic Cold-Finger Device for the Investigation of Ice-Binding Proteins. AB - Ice-binding proteins (IBPs) bind to ice crystals and control their structure, enlargement, and melting, thereby helping their host organisms to avoid injuries associated with ice growth. IBPs are useful in applications where ice growth control is necessary, such as cryopreservation, food storage, and anti-icing. The study of an IBP's mechanism of action is limited by the technological difficulties of in situ observations of molecules at the dynamic interface between ice and water. We describe herein a new, to our knowledge, apparatus designed to generate a controlled temperature gradient in a microfluidic chip, called a microfluidic cold finger (MCF). This device allows growth of a stable ice crystal that can be easily manipulated with or without IBPs in solution. Using the MCF, we show that the fluorescence signal of IBPs conjugated to green fluorescent protein is reduced upon freezing and recovers at melting. This finding strengthens the evidence for irreversible binding of IBPs to their ligand, ice. We also used the MCF to demonstrate the basal-plane affinity of several IBPs, including a recently described IBP from Rhagium inquisitor. Use of the MCF device, along with a temperature-controlled setup, provides a relatively simple and robust technique that can be widely used for further analysis of materials at the ice/water interface. PMID- 27653475 TI - Can Dissipative Properties of Single Molecules Be Extracted from a Force Spectroscopy Experiment? AB - We performed dynamic force spectroscopy of single dextran and titin I27 molecules using small-amplitude and low-frequency (40-240 Hz) dithering of an atomic force microscope tip excited by a sine wave voltage fed onto the tip-carrying piezo. We show that for such low-frequency dithering experiments, recorded phase information can be unambiguously interpreted within the framework of a transparent theoretical model that starts from a well-known partial differential equation to describe the dithering of an atomic force microscope cantilever and a single molecule attached to its end system, uses an appropriate set of initial and boundary conditions, and does not exploit any implicit suggestions. We conclude that the observed phase (dissipation) signal is due completely to the dissipation related to the dithering of the cantilever itself (i.e., to the change of boundary conditions in the course of stretching). For both cases, only the upper bound of the dissipation of a single molecule has been established as not exceeding 3?10(-7)kg/s. We compare our results with previously reported measurements of the viscoelastic properties of single molecules, and we emphasize that extreme caution must be taken in distinguishing between the dissipation related to the stretched molecule and the dissipation that originates from the viscous damping of the dithered cantilever. We also present the results of an amplitude channel data analysis, which reveal that the typical values of the spring constant of a I27 molecule at the moment of module unfolding are equal to 4+/-1.5mN/m, and the typical values of the spring constant of dextran at the moment of chair-boat transition are equal to 30-50mN/m. PMID- 27653476 TI - Identification of HIV-1-Based Virus-like Particles by Multifrequency Atomic Force Microscopy. AB - Virus-like particles (VLPs) have become a promising platform for vaccine production. VLPs are formed by structural viral proteins that inherently self assemble when expressed in a host cell. They represent a highly immunogenic and safe vaccine platform, due to the absence of the viral genome and its high protein density. One of the most important parameters in vaccine production is the quality of the product. A related bottleneck in VLP-based products is the presence of cellular vesicles as a major contaminant in the preparations, which will require the set up of techniques allowing for specific discrimination of VLPs from host vesicular bodies. In this work novel, to our knowledge, multifrequency (MF) atomic force microscopy (AFM) has permitted full structural nanophysical characterization by its access to the virus capsid of the HIV-based VLPs. The assessment of these particles by advanced amplitude modulation frequency modulation (AM-FM) viscoelastic mapping mode has enhanced the imaging resolution of their nanomechanical properties, opening a new window for the study of the biophysical attributes of VLPs. Finally, the identification and differentiation of HIV-based VLPs from cellular vesicles has been performed under ambient conditions, providing, to our knowledge, novel methodology for the monitoring and quality control of VLPs. PMID- 27653474 TI - Domain Organization in the 54-kDa Subunit of the Chloroplast Signal Recognition Particle. AB - Chloroplast signal recognition particle (cpSRP) is a heterodimer composed of an evolutionarily conserved 54-kDa GTPase (cpSRP54) and a unique 43-kDa subunit (cpSRP43) responsible for delivering light-harvesting chlorophyll binding protein to the thylakoid membrane. While a nearly complete three-dimensional structure of cpSRP43 has been determined, no high-resolution structure is yet available for cpSRP54. In this study, we developed and examined an in silico three-dimensional model of the structure of cpSRP54 by homology modeling using cytosolic homologs. Model selection was guided by single-molecule Forster resonance energy transfer experiments, which revealed the presence of at least two distinct conformations. Small angle x-ray scattering showed that the linking region among the GTPase (G domain) and methionine-rich (M-domain) domains, an M-domain loop, and the cpSRP43 binding C-terminal extension of cpSRP54 are predominantly disordered. Interestingly, the linker and loop segments were observed to play an important role in organizing the domain arrangement of cpSRP54. Further, deletion of the finger loop abolished loading of the cpSRP cargo, light-harvesting chlorophyll binding protein. These data highlight important structural dynamics relevant to cpSRP54's role in the post- and cotranslational signaling processes. PMID- 27653477 TI - Ultraslow Water-Mediated Transmembrane Interactions Regulate the Activation of A2A Adenosine Receptor. AB - Water molecules inside a G-protein coupled receptor (GPCR) have recently been spotlighted in a series of crystal structures. To decipher the dynamics and functional roles of internal water molecules in GPCR activity, we studied the A2A adenosine receptor using microsecond molecular-dynamics simulations. Our study finds that the amount of water flux across the transmembrane (TM) domain varies depending on the receptor state, and that the water molecules of the TM channel in the active state flow three times more slowly than those in the inactive state. Depending on the location in solvent-protein interface as well as the receptor state, the average residence time of water in each residue varies from ~O(10(2)) ps to ~O(10(2)) ns. Especially, water molecules, exhibiting ultraslow relaxation (~O(10(2)) ns) in the active state, are found around the microswitch residues that are considered activity hotspots for GPCR function. A continuous allosteric network spanning the TM domain, arising from water-mediated contacts, is unique in the active state, underscoring the importance of slow water molecules in the activation of GPCRs. PMID- 27653478 TI - Cardiac Calcium ATPase Dimerization Measured by Cross-Linking and Fluorescence Energy Transfer. AB - The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation or changes in calcium or ATP. Fluorescence lifetime data are compatible with a model in which PLB interacts with a SERCA homodimer in a stoichiometry of 1:2. Together, these results suggest that SERCA forms constitutive homodimers in live cells and that dimer formation is not modulated by SERCA conformational poise, PLB binding, or PLB phosphorylation. PMID- 27653479 TI - A Dynamic Picture of the Early Events in Nociceptin Binding to the NOP Receptor by Metadynamics. AB - Nociceptin (NCC, also known as FQ (N/OFQ)) is the 17-amino acid neuropeptide, endogenous ligand for the G-protein-coupled receptor (NOP, also known as ORL-1). In this study, starting from the recently reported x-ray structure at pH 7 of NOP in complex with an antagonist, new insights, to our knowledge, on the binding geometry of NCC to NOP have been provided in silico. After a rigid docking of NCC in an alpha-helix conformation, molecular dynamics (MD) and metadynamics (METAD), a method for the analysis of free-energy surfaces (FES), were performed on the protein-peptide complex. Free-energy profiles were obtained as a function of the alpha-helix content of different segments of the 17-mer ligand, and a structural ensemble of conformations of NCC, corresponding to the minimum of the FES, was extracted, thus representing the NCC bound to the inactive form of NOP. The structural features were compared with many known experimental data. The pose of the "message" domain (residues 1-4) of NCC differs from that of the known NOP antagonists, as being slightly slipped deeper inside the protein core. A residual alpha-helix content in the central part of the peptide (residues 4-9) is maintained, whereas the C-terminal segment (residues 13-17) is unstructured and highly flexible. An important stabilization due to interactions with residues D130 and D110 of the receptor has been found, in agreement with the large decrease in agonist potency reported for the D130A and D110A mutants. The importance of the extracellular domain 2 (ECL2) in the selectivity toward the endogenous ligand has been confirmed. A pivotal role for the conserved residue N133 is suggested and further supported by a study of the N133A in silico mutant. Accordingly, N133 can work as a molecular microswitch driving the change between the inactive and active NOP conformations, in the framework of an extended H-bond and water network rearrangement in the deep binding site. PMID- 27653480 TI - Energetics of Ion Permeation in an Open-Activated TRPV1 Channel. AB - Ion channels enable diffusion of ions down physiological electrochemical gradients. Modulation of ion permeation is crucial for the physiological functioning of cells, and misregulation of ion channels is linked to a myriad of channelopathies. The ion permeation mechanism in the transient receptor potential (TRP) ion channel family is currently not understood at an atomistic level. In this work, we employed a simulation strategy for ion permeation (molecular dynamics simulations with bias-exchange metadynamics) to study and compare monovalent (Na(+), K(+)) ion permeation in the open-activated TRP vanniloid-1 (TRPV1) ion channel. Using ~3.6 MUs of simulation trajectories, we obtained atomistic evidence for the nonselective nature of TRPV1. Our analysis shows that solvated monovalent ions permeate through the selectivity filter with comparable energetic barriers via a two-site mechanism. Finally, we confirmed that an intracellular binding site is located between the intracellular gate residues I679 and E684. PMID- 27653481 TI - Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1. AB - The voltage-dependent anion channel 1 (VDAC-1) is an important protein of the outer mitochondrial membrane that transports energy metabolites and is involved in apoptosis. The available structures of VDAC proteins show a wide beta-stranded barrel pore, with its N-terminal alpha-helix (N-alpha) bound to its interior. Electrophysiology experiments revealed that voltage, its polarity, and membrane composition modulate VDAC currents. Experiments with VDAC-1 mutants identified amino acids that regulate the gating process. However, the mechanisms for how these factors regulate VDAC-1, and which changes they trigger in the channel, are still unknown. In this study, molecular dynamics simulations and single-channel experiments of VDAC-1 show agreement for the current-voltage relationships of an "open" channel and they also show several subconducting transient states that are more cation selective in the simulations. We observed voltage-dependent asymmetric distortions of the VDAC-1 barrel and the displacement of particular charged amino acids. We constructed conformational models of the protein voltage response and the pore changes that consistently explain the protein conformations observed at opposite voltage polarities, either in phosphatidylethanolamine or phosphatidylcholine membranes. The submicrosecond VDAC-1 voltage response shows intrinsic structural changes that explain the role of key gating amino acids and support some of the current gating hypotheses. These voltage-dependent protein changes include asymmetric barrel distortion, its interaction with the membrane, and significant displacement of N-alpha amino acids. PMID- 27653482 TI - Single-Molecule Imaging of Nav1.6 on the Surface of Hippocampal Neurons Reveals Somatic Nanoclusters. AB - Voltage-gated sodium (Nav) channels are responsible for the depolarizing phase of the action potential in most nerve cells, and Nav channel localization to the axon initial segment is vital to action potential initiation. Nav channels in the soma play a role in the transfer of axonal output information to the rest of the neuron and in synaptic plasticity, although little is known about Nav channel localization and dynamics within this neuronal compartment. This study uses single-particle tracking and photoactivation localization microscopy to analyze cell-surface Nav1.6 within the soma of cultured hippocampal neurons. Mean-square displacement analysis of individual trajectories indicated that half of the somatic Nav1.6 channels localized to stable nanoclusters ~230 nm in diameter. Strikingly, these domains were stabilized at specific sites on the cell membrane for >30 min, notably via an ankyrin-independent mechanism, indicating that the means by which Nav1.6 nanoclusters are maintained in the soma is biologically different from axonal localization. Nonclustered Nav1.6 channels showed anomalous diffusion, as determined by mean-square-displacement analysis. High-density single-particle tracking of Nav channels labeled with photoactivatable fluorophores in combination with Bayesian inference analysis was employed to characterize the surface nanoclusters. A subpopulation of mobile Nav1.6 was observed to be transiently trapped in the nanoclusters. Somatic Nav1.6 nanoclusters represent a new, to our knowledge, type of Nav channel localization, and are hypothesized to be sites of localized channel regulation. PMID- 27653483 TI - Simulations of Membrane-Disrupting Peptides I: Alamethicin Pore Stability and Spontaneous Insertion. AB - An all-atom molecular dynamics simulation of the archetype barrel-stave alamethicin (alm) pore in a 1,2-dioleoyl-sn-glycero-3-phosphocholine bilayer at 313 K indicates that ~7 MUs is required for equilibration of a preformed 6 peptide pore; the pore remains stable for the duration of the remaining 7 MUs of the trajectory, and the structure factors agree well with experiment. A 5 MUs simulation of 10 surface-bound alm peptides shows significant peptide unfolding and some unbinding, but no insertion. Simulations at 363 and 413 K with a -0.2 V electric field yield peptide insertion in 1 MUs. Insertion is initiated by the folding of residues 3-11 into an alpha-helix, and mediated by membrane water or by previously inserted peptides. The stability of five alm pore peptides at 413 K with a -0.2 V electric field demonstrates a significant preference for a transmembrane orientation. Hence, and in contrast to the cationic antimicrobial peptide described in the following article, alm shows a strong preference for the inserted over the surface-bound state. PMID- 27653484 TI - Simulations of Membrane-Disrupting Peptides II: AMP Piscidin 1 Favors Surface Defects over Pores. AB - Antimicrobial peptides (AMPs) that disrupt bacterial membranes are promising therapeutics against the growing number of antibiotic-resistant bacteria. The mechanism of membrane disruption by the AMP piscidin 1 was examined with multimicrosecond all-atom molecular dynamics simulations and solid-state NMR spectroscopy. The primary simulation was initialized with 20 peptides in four barrel-stave pores in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol bilayer. The four pores relaxed to toroidal by 200 ns, only one porelike structure containing two transmembrane helices remained at 26 MUs, and none of the 18 peptides released to the surface reinserted to form pores. The simulation was repeated at 413 K with an applied electric field and all peptides were surface-bound by 200 ns. Trajectories of surface-bound piscidin with and without applied fields at 313 and 413 K and totaling 6 MUs show transient distortions of the bilayer/water interface (consistent with (31)P NMR), but no insertion to transmembrane or pore states. (15)N chemical shifts confirm a fully surface-bound conformation. Taken together, the simulation and experimental results imply that transient defects rather than stable pores are responsible for membrane disruption by piscidin 1, and likely other AMPs. PMID- 27653486 TI - Optimal Background Estimators in Single-Molecule FRET Microscopy. AB - Single-molecule total internal reflection fluorescence (TIRF) microscopy constitutes an umbrella of powerful tools that facilitate direct observation of the biophysical properties, population heterogeneities, and interactions of single biomolecules without the need for ensemble synchronization. Due to the low signal/noise ratio in single-molecule TIRF microscopy experiments, it is important to determine the local background intensity, especially when the fluorescence intensity of the molecule is used quantitatively. Here we compare and evaluate the performance of different aperture-based background estimators used particularly in single-molecule Forster resonance energy transfer. We introduce the general concept of multiaperture signatures and use this technique to demonstrate how the choice of background can affect the measured fluorescence signal considerably. A new, to our knowledge, and simple background estimator is proposed, called the local statistical percentile (LSP). We show that the LSP background estimator performs as well as current background estimators at low molecular densities and significantly better in regions of high molecular densities. The LSP background estimator is thus suited for single-particle TIRF microscopy of dense biological samples in which the intensity itself is an observable of the technique. PMID- 27653485 TI - Membrane Binding and Oligomerization of the Lipopeptide A54145 Studied by Pyrene Fluorescence. AB - A54145 is a lipopeptide antibiotic related to daptomycin that permeabilizes bacterial cell membranes. Its action requires both calcium and phosphatidylglycerol in the target membrane, and it is accompanied by the formation of membrane-associated oligomers. We here probed the interaction of A54145 with model membranes composed of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol, using the steady-state and time-resolved fluorescence of a pyrene-labeled derivative (Py-A54145). In solution, the labeled peptide was found to exist as a monomer. Its membrane interaction occurred in two stages that could be clearly distinguished by varying the calcium concentration. In the first stage, which was observed between 0.15 and 1 mM calcium, Py-A54145 bound to the membrane, as indicated by a strong increase in pyrene monomer emission. At the same calcium concentration, excimer emission increased also, suggesting that Py-A54145 had oligomerized. A global analysis of the time resolved pyrene monomer and excimer fluorescence confirmed that Py-A54145 forms oligomers quantitatively and concomitantly with membrane binding. When calcium was raised beyond 1 mM, a distinct second transition was observed that may correspond to a doubling of the number of oligomer subunits. The collective findings confirm and extend our understanding of the action mode of A54145 and daptomycin. PMID- 27653487 TI - The Effect of Temperature on Microtubule-Based Transport by Cytoplasmic Dynein and Kinesin-1 Motors. AB - Cytoplasmic dynein and kinesin are both microtubule-based molecular motors but are structurally and evolutionarily unrelated. Under standard conditions, both move with comparable unloaded velocities toward either the microtubule minus (dynein) or plus (most kinesins) end. This similarity is important because it is often implicitly incorporated into models that examine the balance of cargo fluxes in cells and into models of the bidirectional motility of individual cargos. We examined whether this similarity is a robust feature, and specifically whether it persists across the biologically relevant temperature range. The velocity of mammalian cytoplasmic dynein, but not of mammalian kinesin-1, exhibited a break from simple Arrhenius behavior below 15 degrees C-just above the restrictive temperature of mammalian fast axonal transport. In contrast, the velocity of yeast cytoplasmic dynein showed a break from Arrhenius behavior at a lower temperature (~8 degrees C). Our studies implicate cytoplasmic dynein as a more thermally tunable motor and therefore a potential thermal regulator of microtubule-based transport. Our theoretical analysis further suggests that motor velocity changes can lead to qualitative changes in individual cargo motion and hence net intracellular cargo fluxes. We propose that temperature can potentially be used as a noninvasive probe of intracellular transport. PMID- 27653488 TI - A Beetle Flight Muscle Displays Leg Muscle Microstructure. AB - In contrast to major flight muscles in the Mecynorrhina torquata beetle, the third axillary (3Ax) muscle is a minor flight muscle that uniquely displays a powerful mechanical function despite its considerably small volume, ~1/50 that of a major flight muscle. The 3Ax muscle contracts relatively slowly, and in flight strongly pulls the beating wing to attenuate the stroke amplitude. This attenuation leads to left-right turning in flight or wing folding to cease flying. What enables this small muscle to be so powerful? To explore this question, we examined the microstructure of the 3Ax muscle using synchrotron x ray diffraction, optical microscopy, and immunoblotting analysis. We found that the 3Ax muscle has long (~5 MUm) myofilaments and that the ratio of thick (myosin) filaments to thin (actin) filaments is 1:5 or 1:6. These characteristics are not observed in the major flight muscles, which have shorter myofilaments (~3.5 MUm) with a smaller ratio (1:3), and instead are more typical of a leg muscle. Furthermore, the flight-muscle-specific troponin isoform, TnH, is not expressed in the 3Ax muscle. Since such a microstructure is suitable for generating large tension, the 3Ax muscle is appropriately designed to pull the wing strongly despite its small volume. PMID- 27653489 TI - Electrophysiological Determination of Submembrane Na(+) Concentration in Cardiac Myocytes. AB - In the heart, Na(+) is a key modulator of the action potential, Ca(2+) homeostasis, energetics, and contractility. Because Na(+) currents and cotransport fluxes depend on the Na(+) concentration in the submembrane region, it is necessary to accurately estimate the submembrane Na(+) concentration ([Na(+)]sm). Current methods using Na(+)-sensitive fluorescent indicators or Na(+) -sensitive electrodes cannot measure [Na(+)]sm. However, electrophysiology methods are ideal for measuring [Na(+)]sm. In this article, we develop patch clamp protocols and experimental conditions to determine the upper bound of [Na(+)]sm at the peak of action potential and its lower bound at the resting state. During the cardiac cycle, the value of [Na(+)]sm is constrained within these bounds. We conducted experiments in rabbit ventricular myocytes at body temperature and found that 1) at a low pacing frequency of 0.5 Hz, the upper and lower bounds converge at 9 mM, constraining the [Na(+)]sm value to ~9 mM; 2) at 2 Hz pacing frequency, [Na(+)]sm is bounded between 9 mM at resting state and 11.5 mM; and 3) the cells can maintain [Na(+)]sm to the above values, despite changes in the pipette Na(+) concentration, showing autoregulation of Na(+) in beating cardiomyocytes. PMID- 27653490 TI - Topography of Cells Revealed by Variable-Angle Total Internal Reflection Fluorescence Microscopy. AB - We propose an improved version of variable-angle total internal reflection fluorescence microscopy (vaTIRFM) adapted to modern TIRF setup. This technique involves the recording of a stack of TIRF images, by gradually increasing the incident angle of the light beam on the sample. A comprehensive theory was developed to extract the membrane/substrate separation distance from fluorescently labeled cell membranes. A straightforward image processing was then established to compute the topography of cells with a nanometric axial resolution, typically 10-20 nm. To highlight the new opportunities offered by vaTIRFM to quantify adhesion process of motile cells, adhesion of MDA-MB-231 cancer cells on glass substrate coated with fibronectin was examined. PMID- 27653491 TI - Saturation Dynamics Measures Absolute Cross Section and Generates Contrast within a Neuron. AB - The intensity required to optically saturate a chromophore is a molecular property that is determined by its absorption cross section (sigma) and the excited state lifetime. We present an analytical description of such a system and show that fluorescence around the onset of saturation is characterized by product of absorption cross section and lifetime. Using this approach we formulate a generalized method for measuring the multiphoton cross section of fluorophores and use it to obtain the absolute three-photon cross-section spectra of tryptophan. We find that the tryptophan three-photon cross section ranges from 0.28 S.I. units (m(6)s(2)photon(-2)) at 870 nm to 20 S.I. units at 740 nm. Further, we show that the product of molecular rate of excitation and de excitation, denoted as beta, serves as a vital contrasting agent for imaging local environment. Our contrast parameter, beta, is related to fraction of the population present in the excited state and is independent of the fluorophore concentration. We show that beta-imaging can be carried out in a regular two photon microscope setup through a series of intensity scans. Using enhanced green fluorescent protein (EGFP) fluorescence from the brain slices of Thy-1 EGFP transgenic mice, we show that there is an inherent, concentration independent, variation in contrast across the soma and the dendrite. PMID- 27653492 TI - New Biological Frontiers Illuminated by Molecular Sensors and Actuators. PMID- 27653493 TI - Tracheoesophageal fistula: open versus endoscopic repair. AB - PURPOSE OF REVIEW: The management of primary or recurrent tracheoesophageal fistula (TEF) remains an important challenge for airway surgeons. RECENT FINDINGS: The accuracy of prenatal detection can be significantly improved in specialized centers. Routine preoperative and postoperative airway endoscopy is recommended to detect a proximal fistula and evaluate vocal cord motility. Minimally invasive thoracoscopic approaches have equal success and improved cosmesis and visualization as compared with thoracostomy. Novel open approaches for complex TEF include a transcervical, transtracheal approach, and slide tracheoplasty.Endoscopic closure of TEF carries less morbidity. Options include de-epithelialization of the tract, interposed material, and combinations. The mean operative time is 30 min; however multiple treatments are required (average 2.1). Use of continuous positive airway pressure in the immediate postoperative period was not associated with increased leak or recurrence. Children post-TEF repair continue to have frequent gastrointestinal and respiratory symptoms. SUMMARY: Prenatal diagnosis is beneficial both for prenatal counseling and for planning care. The ideal endoscopic approach is undecided but remains an interesting alternative to open surgery provided failures are anticipated and prompt repeated treatments initiated to preclude ongoing respiratory complications. Transtracheal approaches and slide tracheoplasty are well tolerated and effective in complex/recurrent cases. Long-term follow-up of patients with TEF is important. PMID- 27653494 TI - Use of Baby Isao Simulator and Standardized Parents in Hearing Screening and Parent Counseling Education. AB - PURPOSE: The primary purpose of this study was to test the effect of the combined use of trained standardized parents and a baby simulator on students' hearing screening and parental counseling knowledge and skills. METHOD: A one-group pretest-posttest quasi-experimental study design was used to assess self-ratings of confidence in knowledge and skills and satisfaction of the educational experience with standardized parents and a baby simulator. The mean age of the 14 audiology students participating in this study was 24.79 years (SD = 1.58). Participants completed a pre- and postevent questionnaire in which they rated their level of confidence for specific knowledge and skills. Six students (2 students in each scenario) volunteered to participate in the infant hearing screening and counseling scenarios, whereas others participated as observers. All participants participated in the briefing and debriefing sessions immediately before and after each of 3 scenarios. After the last scenario, participants were asked to complete a satisfaction survey of their learning experience using simulation and standardized parents. RESULTS: Overall, the pre- and post simulation event questionnaire revealed a significant improvement in the participants' self-rated confidence levels regarding knowledge and skills. The mean difference between pre- and postevent scores was 0.52 (p < .01). The mean satisfaction level was 4.71 (range = 3.91-5.00; SD = 0.30) based on a Likert scale, where 1 = not satisfied and 5 = very satisfied. CONCLUSIONS: The results of this novel educational activity demonstrate the value of using infant hearing screening and parental counseling simulation sessions to enhance student learning. In addition, this study demonstrates the use of simulation and standardized parents as an important pedagogical tool for audiology students. Students experienced a high level of satisfaction with the learning experience. PMID- 27653495 TI - Patient Safety During Chest Drain Insertion-A Survey of Current Practice. AB - OBJECTIVES: The aim of this study was to identify the degree of awareness of the current guidelines and common practices for pleural drain insertion. METHODS: A 10-item questionnaire was sent electronically to junior physicians from 4 different hospitals in the South Eastern Sydney and Illawarra Shoalhaven Local Health District. Participants were asked to give their level of experience and management practices for chest drain insertion. RESULTS: A total of 94 junior medical officers from 4 hospitals in the district completed the survey. More than 20% had never inserted a chest drain at the time; 72% had primarily learned from bedside teaching and peer learning, but 11% had no training at all. More than 50% of physicians felt that the biggest threat to the procedure was their own lack of confidence for drain insertion. Despite current guidelines, 25% insert chest drains routinely without the aid of ultrasound. A third of interviewees were aware of local guidelines but had not read them. Most physicians (86%) believe that formal standardized training should be available for junior physicians. CONCLUSIONS: Our findings demonstrate the ongoing need for improved procedural training in chest drain insertion, with emphasis on mandatory thoracic ultrasound. We consider it important to continue to raise concern and awareness that chest drain insertion is not a harmless procedure, and further physician procedural competence is required. PMID- 27653496 TI - Identifying Patient Characteristics Associated With Deficits in Surgical Decision Making. AB - BACKGROUND: Patient involvement in surgical decisions is formalized in the informed consent process, which should reflect that the patient understands their diagnosis, planned procedure, and the associated risks and benefits before consenting to treatment. If high-quality shared decision making has occurred, the treatment chosen should best match the goals and preferences of the patient. Little information currently exists that analyzes factors associated with decisional quality in surgery. Identifying patient factors correlated with specific deficits in preoperative decision making is essential for improvement of the shared decision-making process. This study aims to identify patient characteristics and coping strategies associated with the presence of knowledge deficits regarding their diagnosis and procedure so that interventions can be targeted to these vulnerable groups. METHODS: Approximately 882 preoperative patients were assessed regarding understanding of their diagnosis and procedure. Sociodemographic and decision-making variables were evaluated using validated measures. Univariate analysis and logistic regression models assessed factors associated with lower decisional quality. RESULTS: Approximately 136 (15%) of 882 patients had deficits in knowledge of diagnosis and/or procedure. Older patients were more likely to demonstrate these deficits (P = 0.0002). Using multivariate analysis, independent predictors of knowledge deficits included patients who identified themselves as Black, Asian, or other race (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.19-5.85; and OR, 1.88; 95% CI, 1.00-3.55, respectively); were older (OR, 1.02; 95% CI, 1.01-1.04); and used denial as a coping strategy (OR, 2.61; 95% CI, 1.29-5.28). The use of acceptance as a coping strategy negatively predicted knowledge deficits (OR, 0.55; 95% CI, 0.36-0.84). CONCLUSIONS: Specific patient factors and coping strategies are associated with deficiencies in decisional quality. Identifying vulnerable groups at risk for these issues can help target methodologies and resources to ensure high-quality surgical decision making. PMID- 27653497 TI - Tipping the Balance Toward Fewer Antibiotics. PMID- 27653499 TI - The New USA NIH Strategic Plan for Complementary and Integrative Health: Interview with Josephine Briggs, MD. PMID- 27653498 TI - Complications and Failure to Rescue After Inpatient Noncardiac Surgery in the Veterans Affairs Health System. AB - Importance: The quality of surgical care in the Veterans Health Administration improved markedly in the 1990s after implementation of the Veterans Affairs (VA) National Surgical Quality Improvement Program (now called the VA Surgical Quality Improvement Program). Although there have been many recent evaluations of surgical care in the private sector, to date, a contemporary global evaluation has not been performed within the VA health system. Objective: To provide a contemporaneous report of noncardiac postoperative outcomes in the VA health system during the past 15 years. Design, Setting, and Participants: A retrospective cohort study was conducted using data from the VA Surgical Quality Improvement Program among veterans who underwent inpatient general, vascular, thoracic, genitourinary, neurosurgical, orthopedic, or spine surgery from October 1, 1999, through September 30, 2014. Main Outcomes and Measures: Rates of 30-day morbidity, mortality, and failure to rescue (FTR) over time. Results: Among 704 901 patients (mean [SD] age, 63.7 [11.8] years; 676 750 [96%] male) undergoing noncardiac surgical procedures at 143 hospitals, complications occurred in 97 836 patients (13.9%), major complications occurred in 66 816 (9.5%), FTR occurred in 12 648 of the 97 836 patients with complications (12.9%), FTR after major complications occurred in 12 223 of the 66 816 patients with major complications (18.3%), and 18 924 patients (2.7%) died within 30 days of surgery. There were significant decreases from 2000 to 2014 in morbidity (8202 of 59 421 [13.8%] vs 3368 of 32 785 [10.3%]), major complications (5832 of 59 421 [9.8%] vs 2284 of 32 785 [7%]), FTR (1445 of 8202 [17.6%] vs 351 of 3368 [10.4%]), and FTR after major complications (1388 of 5832 [23.8%] vs 343 of 2284 [15%]) (trend test, P < .001 for all). Although there were no clinically meaningful differences in rates of complications and major complications across hospital risk-adjusted mortality quintiles (any complications: lowest quintile, 20 945 of 147 721 [14.2%] vs highest quintile, 18 938 of 135 557 [14%]; major complications: lowest quintile, 14 044 of 147 721 [9.5%] vs highest quintile, 12 881 of 135 557 [9.5%]), FTR rates (any complications: lowest quintile, 2249 of 20 945 [10.7%] vs highest quintile, 2769 of 18 938 [14.6%]; major complications: lowest quintile, 2161 of 14 044 [15.4%] vs highest quintile, 2663 of 12 881 [20.7%]) were significantly higher with increasing quintile (P < .001). However, across hospital quintiles, there were significant decreases in morbidity (20.6%-29.9% decrease; trend test, P < .001 for all) and FTR (29.2%-50.6% decrease; trend test, P < .001 for all) during the study period. After hierarchical modeling, the odds of postoperative mortality, FTR, and FTR after a major complication were approximately 40% to 50% lower in the most recent study year compared with 15 years ago (P < .001 for all). Conclusions and Relevance: For the past 15 years, morbidity, mortality, and FTR have improved within the VA health system. Other integrated health systems providing a high volume of surgical care for their enrollees may benefit by critically evaluating the system-level approaches of the VA health system to surgical quality improvement. PMID- 27653500 TI - Photochemical Nickel-Catalyzed C-H Arylation: Synthetic Scope and Mechanistic Investigations. AB - An iridium photocatalyst and visible light facilitate a room temperature, nickel catalyzed coupling of (hetero)aryl bromides with activated alpha heterosubstituted or benzylic C(sp3)-H bonds. Mechanistic investigations on this unprecedented transformation have uncovered the possibility of an unexpected mechanism hypothesized to involve a Ni-Br homolysis event from an excited-state nickel complex. The resultant bromine radical is thought to abstract weak C(sp3) H bonds to generate reactive alkyl radicals that can be engaged in Ni-catalyzed arylation. Evidence suggests that the iridium photocatalyst facilitates nickel excitation and bromine radical generation via triplet-triplet energy transfer. PMID- 27653501 TI - Genomic alterations in human epidermal growth factor receptor 2 (HER2/ERBB2) in head and neck squamous cell carcinoma. AB - BACKGROUND: Despite recent advances, survival outcomes for those with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) have remained poor. Novel approaches should be investigated to improve outcomes. METHODS: A retrospective chart review was performed of a patient who presented with a TNM classification III HNSCC of the oropharynx, positive for human papillomavirus (HPV) who had a complete response to a human epidermal growth factor receptor 2 (HER2)-targeted therapy. Amplification rates of HER2 in the HNSCC Cancer Genome Atlas Network (TCGA) dataset and the FoundationOne genomic profiling dataset were evaluated. RESULTS: Comprehensive genomic profiling of the tumor obtained from the dermal metastasis identified amplification of HER2. Data from TCGA and FoundationOne showed that the frequency of HER2 alteration was not observed to vary significantly with HPV tumor status. CONCLUSION: This case demonstrates the application of genomic profiling to guide treatments in a patient with HNSCC with advanced metastatic disease refractory to standard of care therapies. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: E15-E19, 2017. PMID- 27653504 TI - A personality and impairment approach to examine the similarities and differences between avoidant personality disorder and social anxiety disorder. AB - The current study examined whether avoidant personality disorder (AvPD) and social anxiety disorder (SAD) should be considered distinct disorder constructs, which is a persistent and controversial issue in the clinical literature. We examined whether relative scores on SAD and AvPD were associated with the same personality profile and severity of impairment. The current research used a cross sectional design and self-report inventories, including multiple measures of personality, impairment and psychopathology. Results from a mixed sample of 402 university and community participants found that scores on AvPD and SAD were similarly associated with personality traits and impairment indices. Moreover, a latent construct accounting for the shared variance for AvPD and SAD was associated with personality traits and impairment, whereas the residuals representing the uniquenesses of these disorder constructs were not. These findings support the view that AvPD and SAD are similar disorders from a phenotypic personality trait and impairment perspective. These findings are contrary to a prevalent view in the literature, known as severity continuum hypothesis, because the two disorders could not be meaningfully differentiated based on severity of impairment. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27653503 TI - Endometriosis and its global research architecture: an in-depth density equalizing mapping analysis. AB - BACKGROUND: Endometriosis is one of the most common gynecological diseases. It is still a chameleon in many aspects and urges intense research activities in the fields of diagnosis, therapy and prevention. Despite the need to foster research in this area, no in-depth analysis of the global architecture of endometriosis research exists yet. METHODS: We here used the NewQIS platform to conduct a density equalizing mapping study, using the Web of Science as database with endometriosis related entries between 1900 and 2009. Density equalizing maps of global endometriosis research encompassing country-specific publication activities, and semi-qualitative indices such as country specific citations, citation rates, h-Indices were created. RESULTS: In total, 11,056 entries related to endometriosis were found. The USA was leading the field with 3705 publications followed by the United Kingdom (952) and Japan (846). Concerning overall citations and country-specific h-Indices, the USA again was the leading nation with 74,592 citations and a modified h-Index of 103, followed by the UK with 15,175 citations (h-Index 57). Regarding the citation rate, Sweden and Belgium were at top positions with rates of 22.46 and 22.26, respectively. Concerning collaborative studies, there was a steep increase in numbers present; analysis of the chronological evolution indicated a strong increase in international collaborations in the past 10 years. CONCLUSIONS: This study is the first analysis that illustrates the global endometriosis research architecture. It shows that endometriosis research is constantly gaining importance but also underlines the need for further efforts and investments to foster research and ultimately improve endometriosis management on a global scale. PMID- 27653502 TI - The Biophysical Basis Underlying Gating Changes in the p.V1316A Mutant Nav1.7 Channel and the Molecular Pathogenesis of Inherited Erythromelalgia. AB - The Nav1.7 channel critically contributes to the excitability of sensory neurons, and gain-of-function mutations of this channel have been shown to cause inherited erythromelalgia (IEM) with neuropathic pain. In this study, we report a case of a severe phenotype of IEM caused by p.V1316A mutation in the Nav1.7 channel. Mechanistically, we first demonstrate that the Navbeta4 peptide acts as a gating modifier rather than an open channel blocker competing with the inactivating peptide to give rise to resurgent currents in the Nav1.7 channel. Moreover, there are two distinct open and two corresponding fast inactivated states in the genesis of resurgent Na+ currents. One is responsible for the resurgent route and practically existent only in the presence of Navbeta4 peptide, whereas the other is responsible for the "silent" route of recovery from inactivation. In this regard, the p.V1316A mutation makes hyperpolarization shift in the activation curve, and depolarization shift in the inactivation curve, vividly uncoupling inactivation from activation. In terms of molecular gating operation, the most important changes caused by the p.V1316A mutation are both acceleration of the transition from the inactivated states to the activated states and deceleration of the reverse transition, resulting in much larger sustained as well as resurgent Na+ currents. In summary, the genesis of the resurgent currents in the Nav1.7 channel is ascribable to the transient existence of a distinct and novel open state promoted by the Navbeta4 peptide. In addition, S4-5 linker in domain III where V1316 is located seems to play a critical role in activation inactivation coupling, chiefly via direct modulation of the transitional kinetics between the open and the inactivated states. The sustained and resurgent Na+ currents may therefore be correlatively enhanced by specific mutations involving this linker and relevant regions, and thus marked hyperexcitability in corresponding neural tissues as well as IEM symptomatology. PMID- 27653505 TI - Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses. AB - BACKGROUND: Current knowledge of human immunological responses to pregnancy associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. METHODS: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5 specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. RESULTS: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. CONCLUSIONS: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria. PMID- 27653506 TI - Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections. AB - It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer's patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum, inhibition of Ca signaling associated with decreased phagosome-lysosome fusion as well as phagocytosis inhibition, bias toward Th2 cell immune response accompanied by cell recruitment, cell proliferation and cell differentiation; leading to persistent infection. Contrarily, MAA infection was related to cellular responses associated with activation of molecular pathways that release chemicals and cytokines involved with containment of infection and a strong bias toward Th1 immune response, resulting in a transient infection. PMID- 27653507 TI - Efficacy and safety of rituximab therapy in patients with pemphigus vulgaris: first report from Turkey. AB - BACKGROUND: Pemphigus vulgaris (PV) is a severe, chronic, and potentially life threatening autoimmune blistering disease that affects the skin and mucous membranes. Rituximab is a monoclonal anti-CD20 antibody which has been used increasingly in the therapy of PV. METHODS: The present study sought to test the efficacy and safety of rituximab as an adjuvant therapy by retrospective analysis of clinical and immunological data for 29 patients with PV who were treated with rituximab between 2010 and 2015. Response to therapy, duration of clinical remission, serology of the response, and adverse effects of rituximab were evaluated. RESULTS: The mean +/- standard deviation (SD) follow-up time was 17.48 +/- 13.18 months. In all patients, findings showed either a decrease in antibody titers or that antibodies were completely undetectable after therapy. Rituximab use resulted in a significant reduction in steroid dosage during follow-up. At the end of the follow-up period, 26 patients (96.2%) had achieved complete remission with or without therapy (one patient had no follow-up and one patient had died, most probably as the result of a thromboembolic event). In 44.4% of patients, a clinical relapse occurred after a mean +/- SD period of 13.1 +/- 4.7 months after the initiation of rituximab therapy. Relapses were managed with additional infusions of rituximab. CONCLUSIONS: Rituximab is a beneficial and relatively safe adjuvant treatment for PV that facilitates prolonged clinical remission and has a significant steroid-sparing effect. PMID- 27653508 TI - A Second, Druggable Binding Site in UDP-Galactopyranose Mutase from Mycobacterium tuberculosis? AB - UDP-galactopyranose mutase (UGM), a key enzyme in the biosynthesis of mycobacterial cell walls, is a potential target for the treatment of tuberculosis. In this work, we investigate binding models of a non-substrate-like inhibitor, MS-208, with M. tuberculosis UGM. Initial saturation transfer difference (STD) NMR experiments indicated a lack of direct competition between MS-208 and the enzyme substrate, and subsequent kinetic assays showed mixed inhibition. We thus hypothesized that MS-208 binds at an allosteric binding site (A-site) instead of the enzyme active site (S-site). A candidate A-site was identified in a subsequent computational study, and the overall hypothesis was supported by ensuing mutagenesis studies of the A-site. Further molecular dynamics studies led us to propose that MS-208 inhibition occurs by preventing complete closure of an active site mobile loop that is necessary for productive substrate binding. The results suggest the presence of an A-site with potential druggability, opening up new opportunities for the development of novel drug candidates against tuberculosis. PMID- 27653509 TI - Myocardial injury in patients with hemodynamic derangements during and/or after liver transplantation. AB - Myocardial injury, defined as an elevation of cardiac troponin (cTn) resulting from ischemia, is associated with substantial mortality in surgical patients, and its incidence, risk factors, and impact on patients undergoing liver transplantation (LT) are poorly understood. In this study, adult patients who experienced perioperative hemodynamic derangements and had cTn measurements within 30 days after LT between 2006 and 2013 were studied. Of 502 patients, 203 (40.4%) met the diagnostic criteria (cTn I >=0.1 ng/mL) of myocardial injury. The majority of myocardial injury occurred within the first three postoperative days and presented without clinical signs or symptoms of myocardial infarction. Thirty day mortality in patients with myocardial injury was 11.4%, significantly higher compared with that in patients without myocardial injury (3.4%, P<.01). Cox analysis indicated the peak cTn was significantly associated with 30-day mortality. Multivariable logistic analysis identified three independent risk factors: requirement of ventilation before transplant (odds ratios (OR) 1.6, P=.006), RBC>=15 units (OR 1.7, P=.006), and the presence of PRS (OR 2.0, P=.028). We concluded that post-LT myocardial injury in this high-risk population was common and associated with mortality. Our findings may be used in pretransplant stratification. Further studies to investigate this postoperative cardiac complication in all LT patients are warranted. PMID- 27653510 TI - Open Microcomedone Extraction Facilitated by Polarized Dermoscopy. AB - Microcomedonal lesions can be aesthetically and psychologically displeasing. The burden of comedones increases when considering their frequency and demand for time-consuming attention. The objective of the current study was to describe a novel technique to facilitate open microcomedone extraction. The instrumentation used includes smartphone photography with dermatoscopy. The dermatoscope is an effective tool for diagnosing a broad range of dermatologic conditions. The polarized dermatoscope can facilitate execution of cutaneous procedures whenever magnification and optimal illumination are necessary. Its connection to a smartphone with a unique adapter enabled single-handed examination of microcomedones. Under magnification with this unit, the involved lesions are photographed to clearly demonstrate the condition and achieve informed consent. The complete procedure can be recorded on video for documentation. In this case, four separate lesions of the left auricle of a young man were treated using direct pressure extraction. The procedure undertaken was rapid, convenient, and completed without any adverse sequelae. This procedure is recommended for similar cases using the dermatoscope, which does not require additional specific training and is readily available at no extra cost. This technique could be used in various dermatologic conditions. PMID- 27653512 TI - Fostering trusting relationships with older immigrants hospitalised for end-of life care. AB - BACKGROUND: Trust has been identified as a vital value in the nurse-patient relationship. Although increasingly the subject of empirical inquiries, the specific processes used by nurses to foster trust in nurse-patient relationships with older immigrants of non-English speaking backgrounds hospitalised for end-of life care have not been investigated. AIMS: To explore and describe the specific processes that nurses use to foster trust and overcome possible cultural mistrust when caring for older immigrants of non-English speaking backgrounds hospitalised for end-of-life care. RESEARCH DESIGN: A qualitative descriptive approach was used. Twenty-two registered nurses were recruited from four metropolitan health services in Melbourne, Australia. Ethical considerations: Research approval was granted by the Human Research Ethics Committees of the host institution and four participating health services. FINDINGS: Thematic analysis revealed that fostering trust encompassed the following three commensurate stages: establishing trust, strengthening trust and sustaining trust. Underpinning the successful achievement of these stages was the nurses' moral commitment (reflected in their intentional, conscious and conscientious approach) to fostering trust as an essential ingredient of quality end-of-life care. DISCUSSION: This study has shown that while professional competencies are important to providing quality end of-life care to older immigrant patients of non-English speaking backgrounds, it is a nurse's moral commitment to fostering trust that may ultimately lay the foundations for a trusting quality care relationship to be established and sustained. CONCLUSION: This study has captured the processes used by nurses to foster trust as an essential element of quality end-of-life care in older immigrants. The characteristics of trust and the different factors influencing its expression in diverse cultural contexts are, however, under-researched. Accordingly, gaps remain in the knowledge and understanding of the specific cultural nuances and manifestations of trust across and within different cultures. This is an area that is germane to further cross-cultural and international collaborative scholarly inquiry and research. PMID- 27653511 TI - Laryngeal T regulatory cells in the setting of smoking and reflux. AB - OBJECTIVES/HYPOTHESIS: The larynx is a mucosal organ rich in lymphatic tissue that is regularly exposed to a multitude of inhaled, ingested, and refluxed microorganisms and irritants. The first line of mucosal immune defense is the barrier, including resident immune cells. T regulatory (Treg) cells are a specialized subset of CD4+ T cells that suppress or dampen immune responses to prevent damaging immunopathology. As Treg cells have been shown to preferentially accumulate at sites of infection, and Treg responses may contribute to persistence of infection by impairing antibacterial immunity, we sought to quantify these cells in laryngeal tissue exposed to smoking and reflux. STUDY DESIGN: Cross-sectional study. METHODS: Using an epigenetic assay, we quantified Treg and T cells and calculated the ratio of Treg to T cells (i.e., cellular ratio of immune tolerance [ImmunoCRIT]) in disease-free laryngeal biopsies representing four inflammatory states: 1) tobacco-exposed tissue, 2) refluxate and tobacco-exposed tissue, 3) refluxate-exposed tissue, and 4) unexposed tissue. RESULTS: There was epigenetic evidence of Treg cells in all tissues, and we found no differences in Treg cell frequency relative to smoking and reflux in laryngeal tissue collected from 42 non-treatment-seeking participants. There was a decrease in total T cell frequency and an increase in ImmunoCRIT values in smokers regardless of reflux status. CONCLUSIONS: In this study, laryngeal tissue from smokers show decreased overall T cells and increased ImmunoCRIT values. Our findings indicate that laryngeal inflammation is not directly mediated by loss of Treg cells in response to smoking and reflux in local tissue and increased ImmunoCRIT values in smokers implicate a role for this environmental exposure in modulating laryngeal immune homeostasis. More studies are indicated to explore Treg cell dysfunction in the pathophysiology of laryngeal disease. LEVEL OF EVIDENCE: NA Laryngoscope, 127:882-887, 2017. PMID- 27653513 TI - Ethics of rationing of nursing care. AB - BACKGROUND: Rationing of various needed services, for example, nursing care, is inevitable due to unlimited needs and limited resources. Rationing of nursing care is considered an ethical issue since it requires judgment about potential conflicts between personal and professional values. OBJECTIVES: The present research sought to explore aspects of rationing nursing care in Iran. RESEARCH DESIGN: This study applied qualitative content analysis, a method to explore people's perceptions of everyday life phenomena and interpret the subjective content of text data. Data collection was performed through in-depth, unstructured, face-to-face interviews with open-ended questions. Participants and research context: The study population included Iranian nurses of all nursing positions, from clinical nurses to nurse managers. Purposive sampling was employed to select 15 female and 3 male nurses (11 clinical nurses, 3 supervisors, 1 matron, 1 nurse, and 2 members of the Nursing Council) working in hospitals of three cities in Iran. Ethical considerations: The study protocol was approved by Tehran University of Medical Sciences (91D1302870). Written informed consent was also obtained from all participants. FINDINGS: According to the participants, rationing of nursing care consisted of two categories, that is, causes of rationing and consequences of rationing. The first category comprised three subcategories, namely, patient needs and demands, routinism, and VIP patients. The three subcategories forming the second category were missed nursing care, patient dissatisfaction, and nurses' feeling of guilt. CONCLUSION: Levels at which healthcare practices are rationed and clarity of the rationing are important structural considerations in the development of an equal, appropriate, and ethical healthcare system. Moreover, the procedure of rationing is critical as it not only influences people's lives but also reflects the values that dominate in the society. Therefore, in order to minimize the negative consequences of rationing of nursing care, further studies on the ethical dimensions of this phenomenon are warranted. PMID- 27653515 TI - Symposium Summaries. PMID- 27653514 TI - Pediatric Pulmonology. PMID- 27653516 TI - Poster Session Abstracts. PMID- 27653518 TI - Program & Papers. PMID- 27653519 TI - Structural and Biochemical Analysis of Protein-Protein Interactions Between the Acyl-Carrier Protein and Product Template Domain. AB - In fungal non-reducing polyketide synthases (NR-PKS) the acyl-carrier protein (ACP) carries the growing polyketide intermediate through iterative rounds of elongation, cyclization and product release. This process occurs through a controlled, yet enigmatic coordination of the ACP with its partner enzymes. The transient nature of ACP interactions with these catalytic domains imposes a major obstacle for investigation of the influence of protein-protein interactions on polyketide product outcome. To further our understanding about how the ACP interacts with the product template (PT) domain that catalyzes polyketide cyclization, we developed the first mechanism-based crosslinkers for NR-PKSs. Through in vitro assays, in silico docking and bioinformatics, ACP residues involved in ACP-PT recognition were identified. We used this information to improve ACP compatibility with non-cognate PT domains, which resulted in the first gain-of-function ACP with improved interactions with its partner enzymes. This advance will aid in future combinatorial biosynthesis of new polyketides. PMID- 27653521 TI - "I would have preferred more options": accounting for non-binary youth in health research. AB - As a research team focused on vulnerable youth, we increasingly need to find ways to acknowledge non-binary genders in health research. Youth have become more vocal about expanding notions of gender beyond traditional categories of boy/man and girl/woman. Integrating non-binary identities into established research processes is a complex undertaking in a culture that often assumes gender is a binary variable. In this article, we present the challenges at every stage of the research process and questions we have asked ourselves to consider non-binary genders in our work. As researchers, how do we interrogate the assumptions that have made non-binary lives invisible? What challenges arise when attempting to transform research practices to incorporate non-binary genders? Why is it crucial that researchers consider these questions at each step of the research process? We draw on our own research experiences to highlight points of tensions and possibilities for change. Improving access to inclusive health-care for non binary people, and non-binary youth in particular, is part of creating a more equitable healthcare system. We argue that increased and improved access to inclusive health-care can be supported by research that acknowledges and includes people of all genders. PMID- 27653520 TI - Nigral and striatal connectivity alterations in asymptomatic LRRK2 mutation carriers: A magnetic resonance imaging study. AB - BACKGROUND: The study of functional connectivity by means of magnetic resonance imaging (MRI) in asymptomatic LRRK2 mutation carriers could contribute to the characterization of the prediagnostic phase of LRRK2-associated Parkinson's disease (PD). The objective of this study was to characterize MRI functional patterns during the resting state in asymptomatic LRRK2 mutation carriers. METHODS: We acquired structural and functional MRI data of 18 asymptomatic LRRK2 mutation carriers and 18 asymptomatic LRRK2 mutation noncarriers, all first degree relatives of LRRK2-PD patients. Starting from resting-state data, we analyzed the functional connectivity of the striatocortical and the nigrocortical circuitry. Structural brain data were analyzed by voxel-based morphometry, cortical thickness, and volumetric measures. RESULTS: Asymptomatic LRRK2 mutation carriers had functional connectivity reductions between the caudal motor part of the left striatum and the ipsilateral precuneus and superior parietal lobe. Connectivity in these regions correlated with subcortical gray-matter volumes in mutation carriers. Asymptomatic carriers also showed increased connectivity between the right substantia nigra and bilateral occipital cortical regions (occipital pole and cuneus bilaterally and right lateral occipital cortex). No intergroup differences in structural MRI measures were found. In LRRK2 mutation carriers, age and functional connectivity correlated negatively with striatal volumes. Additional analyses including only subjects with the G2019S mutation revealed similar findings. CONCLUSIONS: Asymptomatic LRRK2 mutation carriers showed functional connectivity changes in striatocortical and nigrocortical circuits compared with noncarriers. These findings support the concept that altered brain connectivity precedes the onset of classical motor features in a genetic form of PD. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27653522 TI - A qualitative meta-synthesis: public health nurses role in the identification and management of perinatal mental health problems. AB - AIM: To report findings of a systematic review and meta-synthesis of qualitative studies exploring public health nurses' perceptions and experiences of identifying and managing women with perinatal mental health (PMH) problems. BACKGROUND: Public health nurses play a key role in supporting women who experience PMH problems and several qualitative studies have explored their role. DESIGN: Systematic review and meta-synthesis DATA SOURCES: A comprehensive search was developed and multiple databases were searched from 2000-2015. REVIEW METHODS: Studies that employed qualitative methods to explore experiences of public health nurses in identifying and managing women with PMH problems were included. Two reviewers independently assessed the methodological quality of studies. Themes, concepts and interpretations were extracted and synthesized using the process of thematic analysis. RESULTS: Fifteen papers including 14 unique qualitative studies were included. Two overarching themes were identified: 'conceptualization and detection of PMH problems' and 'barriers and facilitators to management'. The former of these comprised several subthemes including the use of formal screening tools vs. clinical intuition and challenges encountered in detection. The latter theme, barriers to management included availability of referral pathways and time. In terms of facilitators, training, public health nursing interventions, support groups and referral pathways were identified as factors that optimize management. CONCLUSIONS: Public health nurses use a variety of methods to identify women with PMH problems. However, several support structures are needed to optimize management including access to appropriate referral pathways, support groups and relationship continuity. PMID- 27653524 TI - Hepatic glucose utilization in hepatic steatosis and obesity. AB - Hepatic steatosis is associated with obesity and insulin resistance. Whether hepatic glucose utilization rate (glucose phosphorylation rate; MRglu) is increased in steatosis and/or obesity is uncertain. Our aim was to determine the separate relationships of steatosis and obesity with MRglu. Sixty patients referred for routine PET/CT had dynamic PET imaging over the abdomen for 30 min post-injection of F-18-fluorodeoxyglucose (FDG), followed by Patlak-Rutland graphical analysis of the liver using abdominal aorta for arterial input signal. The plot gradient was divided by the intercept to give hepatic FDG clearance normalized to hepatic FDG distribution volume (ml/min per 100 ml) and multiplied by blood glucose to give hepatic MRglu (MUmol/min per 100 ml). Hepatic steatosis was defined as CT density of <=40 HU measured from the 60 min whole body routine PET/CT and obesity as body mass index of >=30 kg/m2 Hepatic MRglu was higher in patients with steatosis (3.3+/-1.3 MUmol/min per 100 ml) than those without (1.7+/-1.2 MUmol/min per 100 ml; P<0.001) but there was no significant difference between obese (2.5+/-1.6 MUmol/min per 100 ml) and non-obese patients (2.1+/-1.3 MUmol/min per 100 ml). MRglu was increased in obese patients only if they had steatosis. Non-obese patients with steatosis still had increased MRglu. There was no association between MRglu and chemotherapy history. We conclude that MRglu is increased in hepatic steatosis probably through insulin resistance, hyperinsulinaemia and up-regulation of hepatic hexokinase, irrespective of obesity. PMID- 27653523 TI - Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice. AB - Selenium (Se) is a trace metalloid essential for life, but its nutritional and physiological roles during the aging process remain elusive. While telomere attrition contributes to replicative senescence mainly through persistent DNA damage response, such an aging process is mitigated in mice with inherently long telomeres. Here, weanling third generation telomerase RNA component knockout mice carrying short telomeres were fed a Se-deficient basal diet or the diet supplemented with 0.15 ppm Se as sodium selenate to be nutritionally sufficient throughout their life. Dietary Se deprivation delayed wound healing and accelerated incidence of osteoporosis, gray hair, alopecia, and cataract, but surprisingly promoted longevity. Plasma microRNA profiling revealed a circulating signature of Se deprivation, and subsequent ontological analyses predicted dominant changes in metabolism. Consistent with this observation, dietary Se deprivation accelerated age-dependent declines in glucose tolerance, insulin sensitivity, and glucose-stimulated insulin production in the mice. Moreover, DNA damage and senescence responses were enhanced and Pdx1 and MafA mRNA expression were reduced in pancreas of the Se-deficient mice. Altogether, these results suggest a novel model of aging with conceptual advances, whereby Se at low levels may be considered a hormetic chemical and decouple healthspan and longevity. PMID- 27653525 TI - Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway. AB - Cucurbitacin E (CuE), a potent member of triterpenoid family isolated from plants, has been confirmed as an antitumour agent by inhibiting proliferation, migration and metastasis in diverse cancer. However, the effects and mechanisms of CuE on osteosarcoma (OS) have not been well understood. The present study aimed to test whether CuE could inhibit growth and invasion of OS cells and reveal its underlying molecular mechanism. After various concentrations of CuE treatment, the anti-proliferative effect of CuE was assessed using the cell counting Kit-8 assay. Flow cytometry analysis was employed to measure apoptosis of OS cells. Cell cycle distribution was analysed by propidium iodide staining. Transwell assay was performed to evaluate the effect of CuE on invasion potential of OS cells. The protein levels were measured by western blot. In addition, the potency of CuE on OS cells growth inhibition was assessed in vivo Our results showed that CuE inhibited cell growth and invasion, induced a cell cycle arrest and triggered apoptosis and modulated the expression of cell growth, cell cycle and cell apoptosis regulators. Moreover, CuE inhibited the PI3K/Akt/mTOR pathway and epithelial-mesenchymal transition (EMT), which suppressed the invasion and metastasis of OS. In addition, we also found that CuE inhibited OS cell growth in vivo Taken together, our study demonstrated that CuE could inhibit OS tumour growth and invasion through inhibiting the PI3K/Akt/mTOR signalling pathway. Our findings suggest that CuE can be considered to be a promising anti-cancer agent for OS. PMID- 27653527 TI - Developing the Surface Chemistry of Transparent Butyl Rubber for Impermeable Stretchable Electronics. AB - Transparent butyl rubber is a new elastomer that has the potential to revolutionize stretchable electronics due to its intrinsically low gas permeability. Encapsulating organic electronic materials and devices with transparent butyl rubber protects them from problematic degradation due to oxygen and moisture, preventing premature device failure and enabling the fabrication of stretchable organic electronic devices with practical lifetimes. Here, we report a methodology to alter the surface chemistry of transparent butyl rubber to advance this material from acting as a simple device encapsulant to functioning as a substrate primed for direct device fabrication on its surface. We demonstrate a combination of plasma and chemical treatment to deposit a hydrophilic silicate layer on the transparent butyl rubber surface to create a new layered composite that combines Si-OH surface chemistry with the favorable gas-barrier properties of bulk transparent butyl rubber. We demonstrate that these surface Si-OH groups react with organosilanes to form self-assembled monolayers necessary for the deposition of electronic materials, and furthermore demonstrate the fabrication of stretchable gold wires using nanotransfer printing of gold films onto transparent butyl rubber modified with a thiol-terminated self assembled monolayer. The surface modification of transparent butyl rubber establishes this material as an important new elastomer for stretchable electronics and opens the way to robust, stretchable devices. PMID- 27653526 TI - Prevalence of arterial stiffness and the risk of myocardial diastolic dysfunction in women. AB - The present study determines the prevalence of vascular dysfunction and arterial stiffness (ASt) in a female urban population by measuring the brachial augmentation index (AIx) and aortic pulse wave velocity (PWV). The study tests the hypothesis that the measurement of AIx and PWV is useful in addition to that of traditional cardiovascular risk factors when assessing the risk for left ventricular diastolic dysfunction (LVDD). This cross-sectional study recruited 965 women aged 25-75 years from 12 districts of Berlin. The ASt indices, brachial AIx, aortic PWV and the central blood pressure were measured by an oscillometric method. A randomly selected subgroup (n=343) was examined by echocardiography. Trans-mitral inflow E/A ratio and diastolic mitral annulus velocity (e) were assessed. Questionnaires, medical history and blood sampling were used for the evaluation of individual risk factors. Normal vascular function was found in 55% of the women included. The prevalence of women with pathological AIx only (AIx ? 10%, PWV normal) was 21.5%, whereas 17.9% were affected by increased AIx and PWV (AIx ? -10%, PWV ?9.7 m/s), and 6% with only pathological PWV values. The prevalence of LVDD was 31.7%. LVDD was significantly associated with pathological PWV ? 9.7 m/s [OR: 1.27, 95%CI: 1.02-1.57], age [OR: 4.17, 95%CI: 2.87-6.07] and a waist circumference >80 cm [OR: 3.61, 95%CI: 1.85-7.04] in multiple regression analysis. The high prevalence of markers for vascular dysfunction and ASt in a general female population and their importance as a mediator of diastolic dysfunction should encourage implementation of aortic PWV measurement to improve cardiovascular-risk assessment in particular to identify subclinical myocardial diastolic dysfunction. PMID- 27653528 TI - Automatic car driving detection using raw accelerometry data. AB - Measuring physical activity using wearable devices has become increasingly popular. Raw data collected from such devices is usually summarized as 'activity counts', which combine information of human activity with environmental vibrations. Driving is a major sedentary activity that artificially increases the activity counts due to various car and body vibrations that are not connected to human movement. Thus, it has become increasingly important to identify periods of driving and quantify the bias induced by driving in activity counts. To address these problems, we propose a detection algorithm of driving via accelerometry (DADA), designed to detect time periods when an individual is driving a car. DADA is based on detection of vibrations generated by a moving vehicle and recorded by an accelerometer. The methodological approach is based on short-time Fourier transform (STFT) applied to the raw accelerometry data and identifies and focuses on frequency vibration ranges that are specific to car driving. We test the performance of DADA on data collected using wrist-worn ActiGraph devices in a controlled experiment conducted on 24 subjects. The median area under the receiver-operating characteristic curve (AUC) for predicting driving periods was 0.94, indicating an excellent performance of the algorithm. We also quantify the size of the bias induced by driving and obtain that per unit of time the activity counts generated by driving are, on average, 16% of the average activity counts generated during walking. PMID- 27653529 TI - Comparative evaluation of patients' and physicians' satisfaction with interferon beta-1b therapy. AB - BACKGROUND: Due to the preventive nature of disease-modifying therapies for multiple sclerosis, treatment success particularly depends on adherence to therapeutic regimens and patients' perception of treatment efficacy. The latter is strongly influenced by the confidence in the involved health care professionals and the relationship to the treating physician. METHODS: In this report, we considered physicians' and patients' evaluation of satisfaction with interferon beta-1b treatment efficacy for assessing the congruence in ratings. Data were queried in a study conducted between 2009 and 2013. RESULTS: After 6 months of therapy, > 80 % of the patients and physicians (N = 445) showed high degrees of satisfaction regarding interferon beta-1b treatment, with only few physicians and patients (<=2.0 %) rating "not satisfied". The proportion of patients rating with the same category as their physicians was similar after 6 months (47 % congruence) and at the 24 months/study end visit (49 %). Discrepancies between ratings were observed with respect to study end: for patients with premature study end, more patients and physicians rated being not satisfied with the therapy, accompanied by a considerably lower congruence of 33 % compared to 54 % for patients receiving the therapy for at least 2 years and completing the study regularly. CONCLUSIONS: Regular communication between physicians and patients about their perception of therapy might improve alignment of treatment evaluation and could result in increased therapy persistence. In addition, patients' willingness to perform a long-term therapy - even in the absence of disease symptoms - might be promoted by repeated exchange between health care providers and patients with regard to realistic treatment expectations. TRIAL REGISTRATION: ClinicalTrials.gov NCT00902135 (registered May 13, 2009). PMID- 27653530 TI - Fast analysis of volatile compounds from Lippia citriodora with nanoporous aluminum wire as solid-phase microextraction fibres. AB - In this study, the efficiency of nanoporous aluminium wires as fibres for headspace solid-phase microextraction (HS-SPME) of volatile compounds from Lippia citriodora was investigated and compared with two anodised methods. The prepared fibres are durable with very good chemical and thermal stability which can be coupled to GC and GC/MS. A one at-a-time optimisation strategy was applied for optimising the important extraction parameters such as extraction temperature, extraction time, sample mass and added water. Compared with hydrodistillation (HD), HS-SPME provide the advantages of a small amount of sample, time-saving, simplicity and cheapness. PMID- 27653531 TI - Calls for cycle helmet campaign to reduce injuries to children. AB - TRIAGE NURSES should alert GPs, school nurses and other professionals when children repeatedly attend emergency departments (EDs) with injuries, according to draft guidance. PMID- 27653534 TI - Too many interruptions can affect patient care adversely, study finds. AB - INTERRUPTIONS TO care in emergency departments (EDs) have a negative impact on patient satisfaction, research has found. PMID- 27653533 TI - Total ban on driving after drinking alcohol debated at RCN congress. AB - A BAN on drinking and driving to reduce the number of alcohol-related road deaths was backed by nurses at RCN congress. PMID- 27653535 TI - Preventing and reducing aggression and violence in health and social care Ford Kelvin Preventing and reducing aggression and violence in health and social care Richard Byrt James Dooher M&K L28 280pp 9781905539574 1905539576 [Formula: see text]. AB - This book will find a worthy place in hospital libraries around the country but, because most of the scenarios it presents occur in psychiatric hospitals, its value for emergency department nurses may be more limited. PMID- 27653536 TI - Board's eye view. AB - HISTORICALLY, ACCIDENT and emergency nursing courses were granted regional funding, and nurses who took part in them were given supernumerary status and rotational clinical experience. Today, nurses usually attend such courses on day release, often without study leave or funding. PMID- 27653537 TI - Anthony's textbook of anatomy & physiology Kevin T Patton Anthony's textbook of anatomy & physiology Gary A Thibodeau Elsevier L49.99 1224pp 9780323055390 0323055397 [Formula: see text]. AB - EXCEPTIONALLY WELL presented, this book on anatomy and physiology clarifies complex and difficult material. PMID- 27653539 TI - Diary. AB - Our roundup of what's on. PMID- 27653538 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27653540 TI - Emergency scenarios. AB - The ambulance technician study site, at www.ambulancetechnicianstudy.co.uk , has been devised to help nurses develop their skills and knowledge of how to deal with emergency care scenarios. PMID- 27653542 TI - Learning disabilities. AB - Easyhealth, at www.easyhealth.org.uk , provides a wide range of online educational material, including short films and a list of useful contacts to help healthcare professionals provide timely care to people with learning disabilities who attend emergency departments (EDs) or acute hospitals. PMID- 27653541 TI - Image interpretation. AB - The Norwich image interpretation course website, at www.imageinterpretation.co.uk , is aimed primarily at radiographers who provide a 'red dot' service to EDs. PMID- 27653543 TI - M2-based influenza vaccines: recent advances and clinical potential. AB - INTRODUCTION: Current influenza vaccines can prevent disease caused by influenza viruses but require annual administration and almost yearly reformulation. An attractive alternative approach would be to use a vaccine that provides broad and, ideally, lifelong protection against all influenza A and B virus strains. The extracellular domain of matrix protein 2 (M2e) of influenza A viruses is conserved and thus fits well in such a broadly protective vaccine. Areas covered: Recent advances in M2e vaccine design, the mode of action of M2e-based immunity and clinical progress of M2-based influenza vaccines. Expert commentary: Many M2e vaccine have been successfully tested for efficacy against a panel of divergent influenza viruses in animal models. More recently, clinical studies have been conducted with M2e vaccine candidates, which demonstrated their safety and immunogenicity in humans. Efficacy studies in humans are still needed to provide evidence that an M2e-based vaccine can protect against human influenza. PMID- 27653544 TI - Pulmonary injury at the anhepatic phase without veno-venous bypass in portal hypertensive rats. AB - OBJECTIVE: In order to understand the characterization and evolution of pulmonary injury, a portal hypertension rat model was used to imitate the anhepatic phase during standard orthotopic liver transplantation without veno-venous bypass. METHODS: In this study, 135 healthy male Wistar rats were selected; in which 15 rats were assigned in the normal control (NC) group and the remaining 120 rats were used to establish a recoverable prehepatic portal hypertension model, which were further evenly divided into eight groups after ischemia-reperfusion: portal hypertensive control group (PHTC), R0h, R6h, R12h, R24h, R48h, R72h, and R7d groups. Meanwhile, arterial blood pressure, dry-to-wet weight ratios of the lung, alanine aminotransferase (ALT) level in serum, arterial oxygen pressure (PaO2), and myeloperoxidase (MPO) activity in lung tissue were measured. Morphology changes of the lung were observed using an optical microscope and a transmission electron microscope. RESULTS: The portal hypertension rat model was successfully established three weeks after the first operation. These portal hypertensive rats could withstand 1 hour at the anhepatic phase. Pulmonary injury severity increased to the most at 12-24 hours, and decreased to normal at seven days after reperfusion. CONCLUSION: Ischemia-reperfusion injury is an important mechanism that results in pulmonary injury after liver transplantation. It is safe for portal hypertensive rats to tolerate 1 hour at the anhepatic phase. Pulmonary injury was the most severe within 12-24 hours after ischemia-reperfusion. PMID- 27653545 TI - Factors associated with mortality among patients with active pulmonary tuberculosis requiring intensive care. AB - INTRODUCTION: The aim of this study was to identify patient characteristics and risk factors associated with in-hospital mortality of patients with pulmonary tuberculosis (PTB) requiring intensive care unit (ICU) management. METHODS: A retrospective chart review was conducted of all patients with active PTB admitted to the ICU at Singapore General Hospital, Singapore, between January 2005 and December 2010. RESULTS: There were 2,155 patients with active PTB diagnosed, of whom 83 (3.9%) patients were admitted to the ICU, but eight were excluded because their admission to the ICU was unrelated to PTB. The most common comorbidities were diabetes mellitus (n = 23, 30.7%) and immunocompromised host (n = 25, 33.3%). A few (n = 4, 5.3%) of the patients had HIV coinfection. A majority (n = 67, 89.3%) of patients required mechanical ventilation and the mean duration of mechanical ventilation was 8.05 +/- 14.43 days. Mean duration of ICU stay and hospital stay were 10.23 +/- 15.8 days and 33.7 +/- 50.7 days, respectively. In hospital mortality was 62.7% (n = 47), and 36 of these patients died while in the ICU (ICU mortality, 48.0%). Univariate analysis identified ischaemic heart disease, low albumin, Acute Physiology and Chronic Health Evaluation score, disseminated intravascular coagulation, shock and multiorgan failure as significantly associated with mortality. Multivariate analysis showed that low albumin on the day of ICU admission was the only significant independent predictor of death (p = 0.033). CONCLUSION: In-hospital mortality from active PTB requiring ICU admission was 62.7%, and low albumin was an independent predictor of mortality in this study. PMID- 27653547 TI - Characteristics and Practices of Adults Who Use Tanning Beds in Private Residences. PMID- 27653546 TI - Body mass index and the risk of postoperative cerebrospinal fluid leak following transsphenoidal surgery in an Asian population. AB - INTRODUCTION: Postoperative cerebrospinal fluid (CSF) leak is a serious complication following transsphenoidal surgery for which elevated body mass index (BMI) has been implicated as a risk factor, albeit only in two recent North American studies. Given the paucity of evidence, we sought to determine if this association holds true in an Asian population, where the BMI criteria for obesity differ from the international standard. METHODS: A retrospective study of 119 patients who underwent 123 transsphenoidal procedures for sellar lesions between May 2000 and May 2012 was conducted. Univariate and multivariate logistic regression analyses were performed to investigate the impact of elevated BMI and other risk factors on postoperative CSF leak. RESULTS: 10 (8.1%) procedures in ten patients were complicated by postoperative CSF leak. The median BMI of patients with postoperative leak following transsphenoidal procedures was significantly higher than that of patients without postoperative CSF leak (27.0 kg/m2 vs. 24.6 kg/m2; p = 0.018). Patients categorised as either moderate or high risk under the Asian BMI classification were more likely to suffer from a postoperative leak (p = 0.030). Repeat procedures were also found to be significantly associated with postoperative CSF leak (p = 0.041). CONCLUSION: Elevated BMI is predictive of postoperative CSF leak following transsphenoidal procedures, even in an Asian population, where the definition of obesity differs from international standards. Thus, BMI should be considered in the clinical decision-making process prior to such procedures. PMID- 27653548 TI - Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats. AB - Epidemiological evidence links recurrent dehydration associated with periodic water intake with chronic kidney disease (CKD). However, minimal attention has been paid to the long-term impact of periodic water intake on the progression of CKD and underlying mechanisms involved. Therefore we investigated the chronic effects of recurrent dehydration associated with periodic water restriction on arterial pressure and kidney function and morphology in male spontaneously hypertensive rats (SHR). Arterial pressure increased and glomerular filtration rate decreased in water-restricted SHR. This was observed in association with cyclic changes in urine osmolarity, indicative of recurrent dehydration. Additionally, water-restricted SHR demonstrated greater renal fibrosis and an imbalance in favour of pro-inflammatory cytokine-producing renal T cells compared to their control counterparts. Furthermore, urinary NGAL levels were greater in water-restricted than control SHR. Taken together, our results provide significant evidence that recurrent dehydration associated with chronic periodic drinking hastens the progression of CKD and hypertension, and suggest a potential role for repetitive bouts of acute renal injury driving renal inflammatory processes in this setting. Further studies are required to elucidate the specific pathways that drive the progression of recurrent dehydration-induced kidney disease. PMID- 27653549 TI - Novel anti-EPHA2 antibody, DS-8895a for cancer treatment. AB - Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors. DS-8895a exhibited markedly increased antibody dependent cellular cytotoxicity (ADCC) in vitro and also inhibited tumor growth in EPHA2-positive human breast cancer MDA-MB-231 and human gastric cancer SNU-16 xenograft mouse models. Moreover, DS-8895a in combination with cisplatin (CDDP) showed better efficacy than each of the monotherapies did in the human gastric cancer model. These results suggest that a novel antibody, DS-8895a has therapeutic potential against EPHA2-expressing tumors. PMID- 27653550 TI - Spatial Distribution of the Cannabinoid Type 1 and Capsaicin Receptors May Contribute to the Complexity of Their Crosstalk. AB - The cannabinoid type 1 (CB1) receptor and the capsaicin receptor (TRPV1) exhibit co-expression and complex, but largely unknown, functional interactions in a sub population of primary sensory neurons (PSN). We report that PSN co-expressing CB1 receptor and TRPV1 form two distinct sub-populations based on their pharmacological properties, which could be due to the distribution pattern of the two receptors. Pharmacologically, neurons respond either only to capsaicin (COR neurons) or to both capsaicin and the endogenous TRPV1 and CB1 receptor ligand anandamide (ACR neurons). Blocking or deleting the CB1 receptor only reduces both anandamide- and capsaicin-evoked responses in ACR neurons. Deleting the CB1 receptor also reduces the proportion of ACR neurons without any effect on the overall number of capsaicin-responding cells. Regarding the distribution pattern of the two receptors, neurons express CB1 and TRPV1 receptors either isolated in low densities or in close proximity with medium/high densities. We suggest that spatial distribution of the CB1 receptor and TRPV1 contributes to the complexity of their functional interaction. PMID- 27653551 TI - Retinal expression of small non-coding RNAs in a murine model of proliferative retinopathy. AB - Ocular neovascularization is a leading cause of blindness in proliferative retinopathy. Small non-coding RNAs (sncRNAs) play critical roles in both vascular and neuronal development of the retina through post-transcriptional regulation of target gene expression. To identify the function and therapeutic potential of sncRNAs in retinopathy, we assessed the expression profile of retinal sncRNAs in a mouse model of oxygen-induced retinopathy (OIR) with pathologic proliferation of neovessels. Approximately 2% of all analyzed sncRNAs were significantly altered in OIR retinas compared with normoxic controls. Twenty three microRNAs with substantial up- or down-regulation were identified, including miR-351, -762, -210, 145, -155, -129-5p, -150, -203, and -375, which were further analyzed for their potential target genes in angiogenic, hypoxic, and immune response-related pathways. In addition, nineteen small nucleolar RNAs also revealed differential expression in OIR retinas compared with control retinas. A decrease of overall microRNA expression in OIR retinas was consistent with reduced microRNA processing enzyme Dicer, and increased expression of Alu element in OIR. Together, our findings elucidated a group of differentially expressed sncRNAs in a murine model of proliferative retinopathy. These sncRNAs may exert critical post-transcriptional regulatory roles in regulating pathological neovascularization in eye diseases. PMID- 27653552 TI - The effect of contextual auditory stimuli on virtual spatial navigation in patients with focal hemispheric lesions. AB - Topographical disorientation is a frequent deficit among patients suffering from brain injury. Spatial navigation can be explored in this population using virtual reality environments, even in the presence of motor or sensory disorders. Furthermore, the positive or negative impact of specific stimuli can be investigated. We studied how auditory stimuli influence the performance of brain injured patients in a navigational task, using the Virtual Action Planning Supermarket (VAP-S) with the addition of contextual ("sonar effect" and "name of product") and non-contextual ("periodic randomised noises") auditory stimuli. The study included 22 patients with a first unilateral hemispheric brain lesion and 17 healthy age-matched control subjects. After a software familiarisation, all subjects were tested without auditory stimuli, with a sonar effect or periodic random sounds in a random order, and with the stimulus "name of product". Contextual auditory stimuli improved patient performance more than control group performance. Contextual stimuli benefited most patients with severe executive dysfunction or with severe unilateral neglect. These results indicate that contextual auditory stimuli are useful in the assessment of navigational abilities in brain-damaged patients and that they should be used in rehabilitation paradigms. PMID- 27653553 TI - Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model. AB - Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Abeta), predominantly the Abeta1-42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Abeta1-42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Abeta-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances. PMID- 27653554 TI - Formulation and Coating of Alginate and Alginate-Hydroxypropylcellulose Pellets Containing Ranolazine. AB - The formulation and the coating composition of biopolymeric pellets containing ranolazine were studied to improve their technological and biopharmaceutical properties. Eudragit L100 (EU L100) and Eudragit L30 D-55-coated alginate and alginate-hydroxypropylcellulose (HPC) pellets were prepared by ionotropic gelation using 3 concentrations of HPC (0.50%, 0.65%, and 1.00% wt/wt) and applying different percentages (5%, 10%, 20%, and 30% wt/wt) of coating material. The uncoated pellets were regular in shape and had mean diameter between 1490 and 1570 MUm. The rate and the entity of the swelling process were affected by the polymeric composition: increasing the HPC concentration, the structure of the pellets became more compact and slowed down the penetration of fluids. Coated alginate-HPC formulations were able to control the drug release at neutral pH: a higher quantity of HPC in the system determined a slower release of the drug. The nature of the coating polymer and the coating level applied affected the drug release in acidic environment: EU L100 gave better performance than Eudragit L30 D-55 and the best coating level was 20%. The pellets containing 0.65% of HPC and coated with 20% EU L100 represented the best formulation, able to limit the drug release in acidic environment and to control it at pH 6.8. PMID- 27653555 TI - Space-time variation of respiratory cancers in South Carolina: a flexible multivariate mixture modeling approach to risk estimation. AB - PURPOSE: Many types of cancer have an underlying spatiotemporal distribution. Spatiotemporal mixture modeling can offer a flexible approach to risk estimation via the inclusion of latent variables. METHODS: In this article, we examine the application and benefits of using four different spatiotemporal mixture modeling methods in the modeling of cancer of the lung and bronchus as well as "other" respiratory cancer incidences in the state of South Carolina. RESULTS: Of the methods tested, no single method outperforms the other methods; which method is best depends on the cancer under consideration. The lung and bronchus cancer incidence outcome is best described by the univariate modeling formulation, whereas the "other" respiratory cancer incidence outcome is best described by the multivariate modeling formulation. CONCLUSIONS: Spatiotemporal multivariate mixture methods can aid in the modeling of cancers with small and sparse incidences when including information from a related, more common type of cancer. PMID- 27653556 TI - Adaptive radiation by waves of gene transfer leads to fine-scale resource partitioning in marine microbes. AB - Adaptive radiations are important drivers of niche filling, since they rapidly adapt a single clade of organisms to ecological opportunities. Although thought to be common for animals and plants, adaptive radiations have remained difficult to document for microbes in the wild. Here we describe a recent adaptive radiation leading to fine-scale ecophysiological differentiation in the degradation of an algal glycan in a clade of closely related marine bacteria. Horizontal gene transfer is the primary driver in the diversification of the pathway leading to several ecophysiologically differentiated Vibrionaceae populations adapted to different physical forms of alginate. Pathway architecture is predictive of function and ecology, underscoring that horizontal gene transfer without extensive regulatory changes can rapidly assemble fully functional pathways in microbes. PMID- 27653557 TI - Injuries observed in a prospective transition from traditional to minimalist footwear: correlation of high impact transient forces and lower injury severity. AB - OBJECTIVES: Minimalist running is increasing in popularity based upon a concept that it can reduce impact forces and decrease injury rates. The purpose of this investigation is to identify the rate and severity of injuries in runners transitioning from traditional to minimalist footwear. The secondary aims were to identify factors correlated with injuries. METHODS: Fourteen habitually shod (traditional running shoes) participants were enrolled for this prospective study investigating injury prevalence during transition from traditional running shoes to 5-toed minimalist shoes. Participants were uninjured, aged between 22-41 years, and ran at least twenty kilometers per week in traditional running shoes. Participants were given industry recommended guidelines for transition to minimalist footwear and fit with a 5-toed minimalist running shoe. They completed weekly logs for identification of injury, pain using Visual Analogue Scale (VAS), injury location, and severity. Foot strike pattern and impact forces were collected using 3D motion analysis at baseline, 4 weeks, and 12 weeks. Injuries were scored according to a modified Running Injury Severity Score (RISS). RESULTS: Fourteen runners completed weekly training and injury logs over an average of 30 weeks. Twelve of 14 (86%) runners sustained injuries. Average injury onset was 6 weeks (range 1-27 weeks). Average weekly mileage of 23.9 miles/week prior to transition declined to 18.3 miles/week after the transition. The magnitude of the baseline impact transient peak in traditional shoes and in minimalist shoes negatively correlated with RISS scores (r = -0.45, p = 0.055 and r = -0.53, p = 0.026, respectively). CONCLUSION: High injury rates occurred during the transition from traditional to minimalist footwear. Non-compliance to transition guidelines and high injury rates suggest the need for improved education. High impact transient forces unexpectedly predicted lower modified RISS scores in this population. PMID- 27653558 TI - Evaluation of mitigation measures to reduce hydropeaking impacts on river ecosystems - a case study from the Swiss Alps. AB - New Swiss legislation obligates hydropower plant owners to reduce detrimental impacts on rivers ecosystems caused by hydropeaking. We used a case study in the Swiss Alps (hydropower company Kraftwerke Oberhasli AG) to develop an efficient and successful procedure for the ecological evaluation of such impacts, and to predict the effects of possible mitigation measures. We evaluated the following scenarios using 12 biotic and abiotic indicators: the pre-mitigation scenario (i.e. current state), the future scenario with increased turbine capacity but without mitigation measures, and future scenarios with increased turbine capacity and four alternative mitigation measures. The evaluation was based on representative hydrographs and quantitative or qualitative prediction of the indicators. Despite uncertainties in the ecological responses and the future operation mode of the hydropower plant, the procedure allowed the most appropriate mitigation measure to be identified. This measure combines a basin and a cavern at a total retention volume of 80,000m3, allowing for substantial dampening in the flow falling and ramping rates and in turn considerable reduction in stranding risk for juvenile trout and in macroinvertebrate drift. In general, this retention volume had the greatest predicted ecological benefit and can also, to some extent, compensate for possible modifications in the hydropower operation regime in the future, e.g. due to climate change, changes in the energy market, and changes in river morphology. Furthermore, it also allows for more specific seasonal regulations of retention volume during ecologically sensitive periods (e.g. fish spawning seasons). Overall experience gained from our case study is expected to support other hydropeaking mitigation projects. PMID- 27653559 TI - First study on oyster-shell-based phosphorous removal in saltwater - A proxy to effluent bioremediation of marine aquaculture. AB - The efficiency of oyster-shell waste for the removal of phosphorous (P) in saltwater was herein evaluated. For that, different factors were tested, being attained >56% and >98% P removal by natural oyster shell (NOS)-fraction <0.125mm and COS (calcined oyster shell)-fraction 0.5mm, respectively. Adsorption was the main mechanism suggested for NOS, whilst a co-mechanism of precipitation occurred with COS. NOS adsorption was consistent with Langmuir model and followed both the Elovich and Intraparticle Difusion kinetic models. COS followed only Pseudo Second Order and, mainly, the Elovich model. Overall, optimal conditions for P removal from saltwater were established for NOS and COS, which will unquestionably allow to comply with regulated P levels for the discharge of wastewater from saltwater RAS. PMID- 27653560 TI - T1 hyperintensity on brain imaging subsequent to gadolinium-based contrast agent administration: what do we know about intracranial gadolinium deposition? AB - There is growing evidence for the accumulation of gadolinium (Gd) in patients administered with intravenous Gd-based contrast agents, even in the absence of renal impairment. This review of the literature will discuss what has been found to date in cadaveric human studies, clinical studies of patients and from animal models. Evidence for the potential route of entry into the brain will be examined. The current state of knowledge of effects of Gd accumulation in the brain is discussed. We will then discuss what the possible implications may be for the choice of Gd-based contrast agents in clinical practice. PMID- 27653562 TI - Incentives for Clinical Trialists to Share Data. PMID- 27653561 TI - Toward a Shared Vision for Cancer Genomic Data. PMID- 27653563 TI - Data Sharing at a Crossroads. PMID- 27653564 TI - Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. AB - BACKGROUND: Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. METHODS: In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, >=28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. RESULTS: Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. CONCLUSIONS: When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12613000303741 .). PMID- 27653565 TI - Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. AB - BACKGROUND: KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. METHODS: We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). RESULTS: Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (+/-SD) KAF156 terminal elimination half-life was 44.1+/-8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. CONCLUSIONS: KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .). PMID- 27653567 TI - IMAGES IN CLINICAL MEDICINE. Regression of Clubbing after Treatment of Lung Cancer. PMID- 27653566 TI - Primary Sclerosing Cholangitis. PMID- 27653568 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 29-2016. A 53-Year-Old Woman with Pain and a Mass in the Breast. PMID- 27653569 TI - The Importance - and the Complexities - of Data Sharing. PMID- 27653570 TI - Engineering Reversal - Finding an Antidote for Direct Oral Anticoagulants. PMID- 27653571 TI - Obesity and Management of Weight Loss. PMID- 27653572 TI - Blood-Pressure and Cholesterol Lowering in the HOPE-3 Trial. PMID- 27653573 TI - Blood-Pressure and Cholesterol Lowering in the HOPE-3 Trial. PMID- 27653574 TI - Blood-Pressure and Cholesterol Lowering in the HOPE-3 Trial. PMID- 27653575 TI - Blood-Pressure and Cholesterol Lowering in the HOPE-3 Trial. PMID- 27653576 TI - Blood-Pressure and Cholesterol Lowering in the HOPE-3 Trial. PMID- 27653577 TI - Acute HIV-1 Infection in Adults in East Africa and Thailand. PMID- 27653578 TI - Acute HIV-1 Infection in Adults in East Africa and Thailand. PMID- 27653579 TI - Elimination of Taenia solium Transmission in Peru. PMID- 27653580 TI - Elimination of Taenia solium Transmission in Peru. PMID- 27653581 TI - Upper Gastrointestinal Bleeding Due to a Peptic Ulcer. PMID- 27653582 TI - Upper Gastrointestinal Bleeding Due to a Peptic Ulcer. PMID- 27653583 TI - Upper Gastrointestinal Bleeding Due to a Peptic Ulcer. PMID- 27653584 TI - The Hidden Lesion. PMID- 27653585 TI - The Hidden Lesion. PMID- 27653586 TI - More on Viral Bronchiolitis in Children. PMID- 27653587 TI - More on Viral Bronchiolitis in Children. PMID- 27653588 TI - Weight Gain over the Holidays in Three Countries. PMID- 27653590 TI - Viral Bronchiolitis in Children. PMID- 27653589 TI - Prolonged Shedding of Zika Virus Associated with Congenital Infection. PMID- 27653591 TI - IMAGES IN CLINICAL MEDICINE. In Vitro Exflagellation of Plasmodium vivax. PMID- 27653592 TI - Participants' Role Expectations in Genetics Research and Re-consent: Revising the Theory and Methods of Mental Models Research Relating to Roles. AB - The rise of large cohort-based health research that includes genetic components has increased the communication challenges for researchers. Controversies have been amplified over requirements for re-consent, return of results, and privacy protections, among other issues. This study extended research on the impact that the perceived role of "research participant" might have on communication expectations to illuminate research participants' preferences for re-consent. The study employed an online survey of participants in a long-standing cancer genetics registry. Results confirmed previous exploratory findings that research participants endorse multiple mental models of participant roles in research (doctor-patient, collaborator, donor, legal contract, etc.). Regression analyses indicated that high and low salience of different models of the role of research participant are related to different communication expectations. However, the pattern of relationships among roles is relevant. The results of the regression analysis also indicated that preference for mandatory re-consent and its relationship to mental models of roles are related to attitudes of trust, benefits, and informational risks. The discussion identifies implications as including the use of explicit approaches to address role relationships in communication with research participants. It also points to implications for methodological approaches in mental model research. PMID- 27653593 TI - Gene Expression Patterns Are Altered in Athymic Mice and Metabolic Syndrome Factors Are Reduced in C57BL/6J Mice Fed High-Fat Diets Supplemented with Soy Isoflavones. AB - Soy isoflavones exert beneficial health effects; however, their potential to ameliorate conditions associated with the metabolic syndrome (MetS) has not been studied in detail. In vitro and in vivo models were used to determine the effect of isoflavones on lipid metabolism, inflammation, and oxidative stress. In nude mice, consumption of Novasoy (NS) increased cholesterol and lipid metabolism gene expression, including Scd-1 (27.7-fold), Cyp4a14 (35.2-fold), and Cyp4a10 (9.5 fold), and reduced anti-inflammatory genes, including Cebpd (16.4-fold). A high fat (HF) diet containing 0.4% (w/w) NS for 10 weeks significantly reduced percent weight gain (74.6 +/- 2.5 vs 68.6 +/- 3.5%) and hepatic lipid accumulation (20 +/ 1.2 vs 27 +/- 1.5%), compared to HF alone (p < 0.05) in C57BL/6J mice. NS also increased lipid oxidation and antioxidant gene expression while decreasing inflammatory cytokines. In vitro analysis in HepG2 cells revealed that genistein dose-dependently decreases oleic acid-induced lipid accumulation. Soy isoflavones may ameliorate symptoms associated with MetS via anti-inflammatory, antioxidant, and hypolipidemic modulation. PMID- 27653594 TI - Multiple Curricula for B Cell Developmental Programming. AB - B-1 B cells differ from conventional B-2 B cells functionally, but how these differences relate to the ontogeny of these lineages has been unclear. Two recent Immunity articles, Kristiansen et al. (2016) and Montecino-Rodriguez et al. (2016), now provide insight into the origins of B-1 and B-2 B cells, revealing a multi-layered developmental program and successive waves of B cell precursors. PMID- 27653595 TI - Looping around Bcl6 in Germinal Center to Sharpen B Cell Immunity. AB - We are beginning to understand the function of 3D genome architecture in the immune system. In this issue, Bunting et al. (2016) reported massive multi-layer genome reorganization from naive B cells to germinal center B cells, centered on a locus control region of Bcl6. PMID- 27653596 TI - Identity Crisis: CD301b(+) Mononuclear Phagocytes Blur the M1-M2 Macrophage Line. AB - Obesity shifts the immune phenotype from M2 macrophage polarization to M1, which causes metabolic dysfunction. In this issue of Immunity, Kumamoto et al. (2016) identify a tissue-resident mononuclear phagocyte population that promotes weight gain and glucose intolerance but are defined by the M2 marker CD301b. PMID- 27653597 TI - HSC Contribution in Making Steady-State Blood. AB - In homeostasis, whether blood cells are derived from committed progenitor or mutipotent stem cell activity remains controversial. In this issue of Immunity, Sawai et al. (2016) describe murine HSCs as the major contributor to the maintenance of multilineage hematopoiesis, both in the steady state and during cytokine response. PMID- 27653598 TI - CD8(+) T Cells and cART: A Dynamic Duo? AB - A new macaque study by Cartwright et al. (2016) suggests that CD8(+) T cells could play a previously unrecognized role in the suppression of HIV-1 during ongoing antiretroviral therapy. PMID- 27653599 TI - Homegrown Macrophages. AB - Macrophages residing in different organs have diverse gene-expression programs. Mass et al. (2016) propose that this diversity develops "at home"-within those organs-after the recruitment of a common precursor that had not made prior commitments to diversity. PMID- 27653602 TI - The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction. PMID- 27653603 TI - The QuEChERS Approach for the Determination of Pesticide Residues in Soil Samples: An Overview. AB - Soil samples are complex matrixes; therefore, soil sample preparation is a critical step, and one that is usually expensive, time-consuming, and labor intensive. The quick, easy, cheap, effective, rugged, and safe (QuEChERS) method, originally developed for the determination of pesticides in fruits and vegetables, has been recently modified and adopted for the analysis of pesticides in soil. This paper reviews all aspects of sample preparation, including extraction and clean-up, and describes the applications of conventional and modified QuEChERS techniques. It also presents a comparison of the QuEChERS method with other methods used for sample preparation for determination of pesticides in soil. PMID- 27653604 TI - Intraoperative management of anterior capsular tear. AB - PURPOSE OF REVIEW: The article reviews the current literature on intraoperative techniques to properly manage anterior capsular tears during cataract surgery. RECENT FINDINGS: Femtosecond laser-assisted cataract surgery creates a more consistent capsulorhexis than traditional capsulotomies, but can also present with new challenges. Irregularities, like microadhesions and tags, can lead to anterior tears if not properly treated. New technology, like the Zepto (Mynosys, Fremont, CA, USA) pulse precision capsulotomy, may produce a smoother edge and reduce the incidence of capsular tears. However, there are novel rescue techniques in the case that a tear-out does occur. SUMMARY: Anterior capsular tears can occur at any stage of cataract surgery. The proper management of these tears will prevent them from extending into the posterior capsule and compromising the structural integrity of the capsular bag. This is essential for endocapsular placement of artificial lenses and for optimal visual outcomes for the patient. PMID- 27653601 TI - CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy. AB - Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals. PMID- 27653600 TI - Germinal Center B Cell Dynamics. AB - Germinal centers (GCs) are the site of antibody diversification and affinity maturation and as such are vitally important for humoral immunity. The study of GC biology has undergone a renaissance in the past 10 years, with a succession of findings that have transformed our understanding of the cellular dynamics of affinity maturation. In this review, we discuss recent developments in the field, with special emphasis on how GC cellular and clonal dynamics shape antibody affinity and diversity during the immune response. PMID- 27653605 TI - Update on congenital cataract surgery management. AB - PURPOSE OF REVIEW: The basic procedure of pediatric cataract surgery has not dramatically changed over the past few years. Recent multicenter study results along with technological innovations, however, have increased our understanding and armamentarium of techniques and devices used to improve outcomes. RECENT FINDINGS: We review surgical techniques that have been recently applied to the management of pediatric cataracts and describe newer intraocular lenses that have become available for use in the pediatric population. The 5-year results of the Infant Aphakia Treatment Study, including visual outcomes and complications, as well as other studies comparing intraocular lens implants with contact lenses for infants have shaped our management of congenital cataract. We also discuss how ocular imaging with optical coherence tomography has enhanced our understanding of the microstructural effects on pediatric eyes after cataract surgery and touch on other future innovations. SUMMARY: We review updates in the management of congenital cataract, which remains a major cause of preventable childhood blindness. PMID- 27653606 TI - Clinical outcomes after injection of a compounded pharmaceutical for prophylaxis after cataract surgery: a large-scale review. AB - PURPOSE OF REVIEW: To evaluate relevant clinical outcomes following a transzonular intravitreal injection of a compounded triamcinolone-moxifloxacin vancomycin (TMV) formulation for postoperative prophylaxis after cataract surgery in a retrospective review of medical records from a private practice, single specialty ambulatory center in New Jersey, USA. RECENT FINDINGS: The analysis included 1541 cases from 922 patients who underwent cataract surgery with an intravitreal injection of TMV from November 2013 to December 2014. Cataract surgery was performed by a standard clear corneal phacoemulsification technique. Transzonular injection was used to deliver TMV directly into the anterior vitreous after implantation of an intraocular lens. SUMMARY: There were no major intraoperative complications associated with the transzonular injection technique. There were no cases of postoperative endophthalmitis. Nearly 92% of cases (n = 1413/1541) did not require supplemental medication after surgery. The rate of breakthrough inflammation at Days 14-21 was 9.2% (n = 132/1429). The rate of visually significant postoperative cystoid macular edema was 2.0% (n = 28/1429). The rate of clinically significant postoperative intraocular pressure increase was low: 0.9% (n = 13/1425) of cases had an at least 10 mmHg increase at Days 14-21 or 90. Four of these cases had intraocular pressure at least 30 mmHg. The rates of infection and inflammation reported in this retrospective review of a transzonular injection of TMV for prophylaxis after cataract surgery appear similar to reported rates with alternative prophylactic therapies such as topical drops. The transzonular injection of TMV may have advantages in terms of patient compliance. PMID- 27653607 TI - Floppy iris syndrome and cataract surgery. AB - PURPOSE OF REVIEW: Intraoperative floppy iris syndrome (IFIS) occurs in 2% of cataract surgeries and is associated with an increased risk of surgical complications. These complications can be avoided when high-risk patients are identified by preoperative screening and appropriate measures are used intraoperatively. The purpose of this article is to review emerging risk factors for IFIS and to summarize management strategies used in IFIS. RECENT FINDINGS: Although alpha1-antagonists in general, and tamsulosin (Flomax, Jalyn) in particular, have long been associated with IFIS, recent studies have more firmly demonstrated the elevated risk of IFIS attributed to tamsulosin. This resulted in a revision of the American Society of Cataract and Refractive Surgery/American Academy of Ophthalmology guidelines on IFIS. Our understanding of additional medications and medical conditions involved in IFIS is also evolving, including an appreciation that women are also susceptible to IFIS. New modifications of techniques used in the intraoperative management of IFIS are also discussed. SUMMARY: Preoperative screening should include both men and women. Current or prior use of alpha1-antagonists and antipsychotics should be documented, along with hypertension. Surgeons should be prepared to employ a range of perioperative interventions in a graded response to IFIS of different severities. PMID- 27653608 TI - Benefits and barriers of accommodating intraocular lenses. AB - PURPOSE OF REVIEW: Presbyopia and cataract development are changes that ubiquitously affect the aging population. Considerable effort has been made in the development of intraocular lenses (IOLs) that allow correction of presbyopia postoperatively. The purpose of this review is to examine the benefits and barriers of accommodating IOLs, with a focus on emerging technologies. RECENT FINDINGS: True accommodation of an IOL involves a dynamic increase in dioptric power to affect a shift from distance to intermediate or near focus. The Crystalens (Crystalens Bausch and Lomb, Inc., Rochester, NY, USA) was the first IOL labeled by the FDA as an accommodating IOL. Further studies have suggested that the Crystalens and several other single optic presbyopia-correcting IOLs may be providing improved intermediate or near vision predominantly through pseudoaccommodative mechanisms, in addition to small changes in axial translation. In light of these findings, a more objective demonstration of accommodation is now required for an IOL to have an accommodative label. Newer technology accommodating IOLs in development have embraced design strategies using dual optics, shape-changing optics, and IOLs with dynamic changes in refractive index. Prevention and treatment algorithms for capsular contraction syndromes unique to Crystalens and Trulign IOL designs will be discussed. SUMMARY: Accommodating IOLs that are in current use are constrained by their low and varied amplitude of accommodation. Such limitations may be circumvented in the future by accommodative design strategies that rely more on shape-related changes in the surfaces of the IOLs or in dynamic changes in refractive index than by forward translation alone. PMID- 27653609 TI - Five-Year Hearing Outcomes in Bilateral Simultaneously Cochlear-Implanted Adult Patients. AB - OBJECTIVE: To report the speech performance and sound localization in adult patients 5 years after bilateral simultaneous cochlear implantation and to evaluate the change in speech scores between 1 and 5 years. DESIGN: In this prospective multicenter study, 26 patients were evaluated 5 years after implantation using long straight electrode arrays (MED-EL Combi 40+, standard electrode array, 31 mm). Speech perception was measured using disyllabic words in quiet and noise, with the speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Speech localization measurements were performed in noise under the same test conditions. These results were compared to those obtained at 1 year reported in a previous study. RESULTS: Five years after implantation, an improvement in speech performance scores compared to 1 year after implantation was found for the poorer ear both in quiet and in noise (+12.1 +/- 2.6%, p < 0.001). The lower the speech score of the poorer ear at 1 year, the greater the improvement at 5 years, both in quiet (r = -0.62) and at a signal-to-noise ratio of +15 dB (r = -0.58). The sound localization on the horizontal plane in noise provided by bilateral implantation was better than the unilateral one and remained stable after the results observed at 1 year. CONCLUSION: In adult patients simultaneously and bilaterally implanted, the poorest speech scores improved between 1 and 5 years after implantation. These findings are an additional element to recommend bilateral implantation in adult patients. The use of both cochlear implants and speech training sessions for patients with poor performance should continue in the period after 1 year following implantation, since the speech scores will improve over time. PMID- 27653610 TI - Repeated Oral or Subcutaneous LMWH Has similar Antithrombotic Activity in a Rat Venous Thrombosis Model: Antithrombotic Activity Correlates With Heparin on Endothelium When Orally Administered. AB - Low-molecular-weight heparins (LMWHs) endure as important drugs for thromboprophylaxis. Although clinical use relies on the subcutaneous (SC) route, our previous studies show that single-dose orally administered LMWHs have antithrombotic activity. Since thromboprophylaxis requires long-term treatment, we examined antithrombotic effects of subacute oral LMWHs in a rat venous thrombosis model and compared results to SC or single-dose oral administration. We measured LMWH in endothelium and plasma, weight change and complete blood counts (CBC). Oral LMWH tinzaparin (3 * 0.1 mg/kg/12 or 24 hours) or reviparin (3 * 0.025 mg/kg/24 hours) significantly decreased thrombosis compared to saline. In the subacute study (60 * 0.1 mg/kg/12 hours), oral or SC tinzaparin significantly reduced thrombosis compared to saline but not to single or 3 * 0.1 mg/kg/12 hours oral tinzaparin. Antithrombotic effects were similar between oral and SC administration. LMWH was found on endothelium following oral but not SC administration. Endothelial concentrations were significantly correlated with incidence of stable thrombi ( P = 0.021 and 0.04 for aortic and vena cava endothelium respectively, chi2 test) and total thrombi ( P = 0.003 for vena cava endothelium). Anti-Xa activity was significantly greater for oral or SC LMWH than saline and significantly greater for SC versus oral LMWH. Values for CBCs were within normal ranges (mean +/- 2 SD). There was no evidence of bleeding. Weight gain was similar between groups. In conclusion, subacute oral and SC LMWH have similar antithrombotic effects. Antithrombotic activity with oral administration is correlated with endothelial LMWH concentrations but not with plasma anticoagulant activity. PMID- 27653611 TI - Executive Functions in Children With Specific Language Impairment: A Meta Analysis. AB - Purpose: Mounting evidence demonstrates deficits in children with specific language impairment (SLI) beyond the linguistic domain. Using meta-analysis, this study examined differences in children with and without SLI on tasks measuring inhibition and cognitive flexibility. Method: Databases were searched for articles comparing children (4-14 years) with and without SLI on behavioral measures of inhibition or cognitive flexibility. Weighted average effect size was calculated using multilevel modeling to measure potential group differences. Results: The analysis included 46 studies. Of those, 34 included inhibitory control measures and 22 included cognitive flexibility tasks. Children with SLI performed below same-aged peers on both inhibitory control tasks (g = -.56) and cognitive flexibility tasks (g = -.27). Moderator analyses showed no effect of linguistic task demands, participant age, or severity of language impairment on the degree of difference between children with SLI and controls on measures of inhibitory control. Conclusion: Reliable differences between children with and without SLI were found on inhibition and cognitive flexibility tasks. A moderate group effect was found for inhibition tasks, but there was only a small effect for cognitive flexibility tasks. Results of moderator analyses suggest that these deficits are present throughout development despite task demands or severity of linguistic impairment. PMID- 27653612 TI - To Maintain Pediatric Competence, Walk With Our Patients and Families. PMID- 27653613 TI - Inclusion of Hypoglycemia in Clinical Practice Guidelines and Performance Measures in the Care of Patients With Diabetes. PMID- 27653614 TI - Automatic segmentation of mandibular canal in cone beam CT images using conditional statistical shape model and fast marching. AB - PURPOSE: Accurate segmentation of the mandibular canal in cone beam CT data is a prerequisite for implant surgical planning. In this article, a new segmentation method based on the combination of anatomical and statistical information is presented to segment mandibular canal in CBCT scans. METHODS: Generally, embedding shape information in segmentation models is challenging. The proposed approach consists of three main steps as follows: At first, a method based on low rank decomposition is proposed for preprocessing. Then, a conditional statistical shape model is trained, and mandibular bone is segmented with high accuracy. In the final stage, fast marching with a new speed function is utilized to find the optimal path between mandibular and mental foramen. Fast marching tries to find the darkest tunnel close to the initial segmentation of the canal, which was obtained with conditional SSM model. In this regard, localization of mandibular canal is performed more accurately. RESULTS: The method is applied to the identification of mandibular canal in 120 sets of CBCT images. Conditional statistical model is evaluated by calculating the compactness capacity, specificity and generalization ability measures. The capability of the proposed model is evaluated in the segmentation of mandibular bone and canal. The framework is effective in noisy scans and is able to detect canal in cases with mild bone resorption. CONCLUSION: Quantitative analysis of the results shows that the method performed better than two other recent methods in the literature. Experimental results demonstrate that the proposed framework is effective and can be used in computer-guided dental implant surgery. PMID- 27653615 TI - Evaluation of a robotic system for irreversible electroporation (IRE) of malignant liver tumors: initial results. AB - OBJECTIVE: Comparison of conventional CT-guided manual irreversible electroporation (IRE) of malignant liver tumors and a robot-assisted approach regarding procedural accuracy, intervention time, dose, complications, and treatment success. METHODS: A retrospective single-center analysis of 40 cases of irreversible electroporation of malignant liver tumors in 35 patients (6 females, 29 males, average age 60.3 years). Nineteen of these ablation procedures were performed manually and 21 with robotic assistance. A follow-up (ultrasound, CT, and MRI) was performed after 6 weeks in all patients. RESULTS: The time from the planning CT scan to the start of the ablation as well as the dose-length product were significantly lower under robotic assistance (63.5 vs. 87.4 min, [Formula: see text]; 2132 vs. 4714 mGy cm, [Formula: see text]). The procedural accuracy, measured as the deviation of the IRE probes with respect to a defined reference probe, was significantly higher using robotic guidance (2.2 vs. 3.1 mm, [Formula: see text]). There were no complications. There was one incomplete ablation in the manual group. CONCLUSION: Robotic assistance for IRE of liver tumors allows for faster procedure times with higher accuracy while reducing radiation dose as compared to the manual placement of IRE probes. PMID- 27653616 TI - A framework for automatic creation of gold-standard rigid 3D-2D registration datasets. AB - PURPOSE: Advanced image-guided medical procedures incorporate 2D intra interventional information into pre-interventional 3D image and plan of the procedure through 3D/2D image registration (32R). To enter clinical use, and even for publication purposes, novel and existing 32R methods have to be rigorously validated. The performance of a 32R method can be estimated by comparing it to an accurate reference or gold standard method (usually based on fiducial markers) on the same set of images (gold standard dataset). Objective validation and comparison of methods are possible only if evaluation methodology is standardized, and the gold standard dataset is made publicly available. Currently, very few such datasets exist and only one contains images of multiple patients acquired during a procedure. To encourage the creation of gold standard 32R datasets, we propose an automatic framework. METHODS: The framework is based on rigid registration of fiducial markers. The main novelty is spatial grouping of fiducial markers on the carrier device, which enables automatic marker localization and identification across the 3D and 2D images. RESULTS: The proposed framework was demonstrated on clinical angiograms of 20 patients. Rigid 32R computed by the framework was more accurate than that obtained manually, with the respective target registration error below 0.027 mm compared to 0.040 mm. CONCLUSION: The framework is applicable for gold standard setup on any rigid anatomy, provided that the acquired images contain spatially grouped fiducial markers. The gold standard datasets and software will be made publicly available. PMID- 27653618 TI - Erratum. PMID- 27653617 TI - Association of biofilm production with colonization among clinical isolates of Acinetobacter baumannii. AB - BACKGROUND/AIMS: The pathogen Acinetobacter baumannii is increasingly causing healthcare-associated infections worldwide, particularly in intensive care units. Biofilm formation, a factor contributing to the virulence of A. baumannii, is associated with long-term persistence in hospital environments. The present study investigates the clinical impact of biofilm production on colonization and acquisition after patient admission. METHODS: Forty-nine A. baumannii isolates were obtained between August and November 2013 from Keimyung University Dongsan Medical Center, Daegu, Korea. All isolates were obtained from sputum samples of new patients infected or colonized by A. baumannii. The microtiter plate assay was used to determine biofilm formation. RESULTS: Twenty-four A. baumannii isolates (48%) demonstrated enhanced biofilm formation capacity than that of the standard A. baumannii strain (ATCC 19606). All isolates were resistant to carbapenem, 38 isolates (77%) were collected from patients in an intensive care unit, and 47 isolates (95%) were from patients who had been exposed to antibiotics in the previous month. The median duration of colonization was longer for biofilm-producing isolates than that of the biofilm non-biofilm producing isolates (18 days vs. 12 days, p < 0.05). Simultaneous colonization with other bacteria was more common for biofilm-producing isolates than that for the non biofilm producing isolates. The most prevalent co-colonizing bacteria was Staphylococcus aureus. CONCLUSIONS: Biofilm-producing isolates seem to colonize the respiratory tract for longer durations than the non-biofilm producing isolates. During colonization, biofilm producers promote co-colonization by other bacteria, particularly S. aureus. Additional research is required to determine possible links between biofilm formation and nosocomial infection. PMID- 27653619 TI - Direct intralesional ethanol sclerotherapy of extensive venous malformations with oropharyngeal involvement after a temporary tracheotomy in the head and neck: Initial results. AB - BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of direct intralesional ethanol sclerotherapy for venous malformations (VMs) with oropharyngeal involvement after a temporary tracheotomy. METHODS: A retrospective assessment was carried out to evaluate the efficacy of direct intralesional ethanol sclerotherapy on 21 consecutive patients presenting with extensive VMs involving the oropharynx in the head and neck and who had undergone tracheotomy. RESULTS: Of the 21 patients, 4 were treated once and 17 were treated from 2 to 5 times. The duration of follow-up was, on average, 9.1 months. Of the 21 patients, 7 (33.3%) had complete palliation, whereas the rest (66.7%) achieved partial palliation. Minor complications occurred in 12 of the 21 patients. CONCLUSION: Direct intralesional ethanol sclerotherapy after a temporary tracheotomy is a safe and effective treatment for extensive VMs involving oropharyngeal areas of the head and neck. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 288-296, 2017. PMID- 27653620 TI - Dyspraxia in ASD: Impaired coordination of movement elements. AB - Children with autism spectrum disorders (ASD) have long been known to have deficits in the performance of praxis gestures; these motor deficits also correlate with social and communicative deficits. To date, the precise nature of the errors involved in praxis has not been clearly mapped out. Based on observations of individuals with ASD performing gestures, we hypothesized that the simultaneous execution of multiple movement elements is especially impaired in affected children. We examined 25 school-aged participants with ASD and 25 age matched controls performing seven simultaneous gestures that required the concurrent performance of movement elements and nine serial gestures, in which all elements were performed serially. There was indeed a group * gesture-type interaction (P < 0.001). Whereas both groups had greater difficulty performing simultaneous than serial gestures, children with ASD had a 2.6-times greater performance decrement with simultaneous (vs. serial) gestures than controls. These results point to a potential deficit in the simultaneous processing of multiple inputs and outputs in ASD. Such deficits could relate to models of social interaction that highlight the parallel-processing nature of social communication. Autism Res 2016,. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 648-652. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27653621 TI - Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs. AB - OBJECTIVES: This study was designed to examine the association between loss-of function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. METHODS: A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations in FLG (R501X, 2282del4 and R2447X) most common among northern Europeans. Subjects were examined for symptoms of atopic diseases as well as for lung function, airway responsiveness, and atopy. RESULTS: In the whole population of twins, the risk for AD was significantly increased in individuals with FLG mutations in comparison with wild-type carriers (34.3% vs. 21.8%) after adjustment for possible confounders (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.07 3.41; P = 0.028). A significant association was also observed for persistent AD (OR 2.10, 95% CI 1.02-4.36; P = 0.046). There were no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had developed AD) than in the non carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45 13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). CONCLUSIONS: Filaggrin gene mutations are risk factors for the presence and persistence of AD and explain the discordance of AD within dizygotic twin pairs. PMID- 27653622 TI - Herringbone Pattern and CH-pi Bonding in the Crystal Architecture of Linear Polycyclic Aromatic Hydrocarbons. AB - The herringbone pattern is a pervasive structural motive found in most molecular crystals involving aromatic compounds. A plot of the experimental sublimation enthalpies of members of increasing size of the acene, phenacene and p-phenyl families versus the number of carbons uncovers a linear relationship between the two magnitudes, suggesting a major role of CH-pi bonding. In this work we undertake the task of evaluating the relevance of the edge-to-face interaction (or CH-pi bond) in the overall reticular energy of the crystal, to quantitatively assess the importance of this structural element. Following a heuristic approach, we considered the series of acenes, phenacenes and p-phenyls and analyzed the edge-to-face interaction between the molecules as they occur in the experimental crystal network. Isolation of the relevant molecular dimers allows to incorporate some of the most sophisticated tools of quantum chemistry and get a reliable picture of the isolated bond. When compared to the experimental sublimation energy, our results are conclusive: this sole interaction is the largest contribution to the lattice energy, and definitively dictates the crystal architecture in all the studied cases. Elusive enough, the edge-to-face interaction is mainly dominated by correlation interactions, specifically in the form of dispersion and, to a less extent, of charge-transfer terms. A suggestive picture of the bond has been obtained by displaying the differences in local electron densities calculated by either correlated or non-correlated methods. PMID- 27653624 TI - A study on negative and depressive symptom prevalence in individuals at ultra high risk for psychosis. AB - BACKGROUND: Negative symptoms are known to be present in the prodromal stage of psychotic disorders, yet little is known about their prevalence. Studies examining the presence of negative symptoms in ultra-high risk (UHR) populations have shown some limitations, notably failing to control depression. The objective of this study was to examine the prevalence of negative symptoms in the presence of significant levels of depression and in the absence of such symptoms (primary negative symptoms) over 1 year and to examine differences in negative symptoms in psychosis converters and non-converters. METHODS: Participants were 123 individuals at UHR for the development of psychosis receiving follow-up for a period of 2 years. Negative symptoms and depression were measured using the Scale for the Assessment of Negative Symptoms and the Montgomery-Asberg Depression Scale at baseline, 6 and 12 months post-admission. RESULTS: At baseline, the prevalence of negative symptoms and primary negative symptoms was 76.4% and 32.7%, respectively. Whereas the prevalence of negative symptoms was significantly decreased at 6 months, the prevalence of primary negative symptoms was similar at all time points. Negative symptoms at baseline were not different between later converters and non-converters to psychosis. CONCLUSION: Our findings confirm the presence of secondary and primary negative symptoms in individuals at UHR, but suggest a differential trajectory of both measures over time. Future studies should include larger UHR groups and focus on the investigation of intra-individual changes in primary negative symptoms over time and further explore their potential role for psychosis conversion. PMID- 27653623 TI - Allergen immunotherapy for the prevention of allergy: A systematic review and meta-analysis. AB - BACKGROUND: There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease. METHODS: Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random effects meta-analyses. RESULTS: A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile. CONCLUSIONS: AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT. PMID- 27653625 TI - Sudden Onset of Papular Elastorrhexis After Immunologic Recovery in a Boy with Human Immunodeficiency Virus. AB - Papular elastorrhexis (PE) is an uncommon elastic tissue disorder clinically characterized by the onset of asymptomatic flesh-colored to whitish papules over the trunk and upper limbs in children. Its etiology remains unknown, although isolated familial cases have suggested that acquired and inherited forms of the disease may exist. We present the case of a 13-year-old boy with human immunodeficiency virus who presented with such lesions after immunological recovery from very low CD4+ counts after introducing highly active antiretroviral therapy. Because neutrophils and macrophages are implicated in elastin metabolism and degradation pathways, immune dysregulation might be another etiologic factor to be considered in this rare disease. PMID- 27653626 TI - A cost-effectiveness analysis of nasal surgery to increase continuous positive airway pressure adherence in sleep apnea patients with nasal obstruction. AB - OBJECTIVES/HYPOTHESIS: Nasal surgery has been implicated to improve continuous positive airway pressure (CPAP) compliance in patients with obstructive sleep apnea (OSA) and nasal obstruction. However, the cost-effectiveness of nasal surgery to improve CPAP compliance is not known. We modeled the cost effectiveness of two types of nasal surgery versus no surgery in patients with OSA and nasal obstruction undergoing CPAP therapy. STUDY DESIGN: Cost effectiveness decision tree model. METHODS: We built a decision tree model to identify conditions under which nasal surgery would be cost-effective to improve CPAP adherence over the standard of care. We compared turbinate reduction and septoplasty to nonsurgical treatment over varied time horizons from a third-party payer perspective. We included variables for cost of untreated OSA, surgical cost and complications, improved compliance postoperatively, and quality of life. RESULTS: Our study identified nasal surgery as a cost-effective strategy to improve compliance of OSA patients using CPAP across a range of plausible model assumptions regarding the cost of untreated OSA, the probability of adherence improvement, and a chronic time horizon. The relatively lower surgical cost of turbinate reduction made it more cost-effective at earlier time horizons, whereas septoplasty became cost-effective after a longer timespan. CONCLUSIONS: Across a range of plausible values in a clinically relevant decision model, nasal surgery is a cost-effective strategy to improve CPAP compliance in OSA patients with nasal obstruction. Our results suggest that OSA patients with nasal obstruction who struggle with CPAP therapy compliance should undergo evaluation for nasal surgery. LEVEL OF EVIDENCE: 2c Laryngoscope, 127:977-983, 2017. PMID- 27653628 TI - Folding and Unfolding Kinetics of Unpurified Proteins by Pulse Proteolysis. AB - It has been reported that pulse proteolysis may be used to investigate protein unfolding kinetics in cell lysate. However, the method has not become popular and we could not judge whether or not it is effective for protein folding study. In this work, we examined the folding and unfolding kinetics of a protein and its variants without purification by pulse proteolysis. The unfolding and refolding rates of the unpurified proteins were similar to those of the purified proteins determined by pulse proteolysis and circular dichroism. Furthermore, because we used a super-stable subtilisin as a protease, we could evaluate the kinetics at 50 degrees C. The present work demonstrates the validity of pulse proteolysis for folding and unfolding studies of unpurified proteins. PMID- 27653627 TI - EDA-Fibronectin Originating from Osteoblasts Inhibits the Immune Response against Cancer. AB - Osteoblasts lining the inner surface of bone support hematopoietic stem cell differentiation by virtue of proximity to the bone marrow. The osteoblasts also modify their own differentiation by producing various isoforms of fibronectin (FN). Despite evidence for immune regulation by osteoblasts, there is limited knowledge of how osteoblasts modulate cells of the immune system. Here, we show that extra domain A (EDA)-FN produced by osteoblasts increases arginase production in myeloid-derived cells, and we identify alpha5beta1 as the mediating receptor. In different mouse models of cancer, osteoblasts or EDA-FN was found to up-regulate arginase-1 expression in myeloid-derived cells, resulting in increased cancer growth. This harmful effect can be reduced by interfering with the integrin alpha5beta1 receptor or inhibiting arginase. Conversely, in tissue injury, the expression of arginase-1 is normally beneficial as it dampens the immune response to allow wound healing. We show that EDA-FN protects against excessive fibrotic tissue formation in a liver fibrosis model. Our results establish an immune regulatory function for EDA-FN originating from the osteoblasts and identify new avenues for enhancing the immune reaction against cancer. PMID- 27653629 TI - The Nearest-Neighbor Effect on Random-Coil NMR Chemical Shifts Demonstrated Using a Low-Complexity Amino-Acid Sequence. AB - In NMR experiments, the chemical shift is typically the first parameter measured and is a source of structural information for biomolecules. Indeed, secondary chemical shifts, the difference between the measured chemical shifts and those expected for a randomly oriented sequence of peptides (the "random coil"), are correlated with the secondary structure of proteins; secondary shift analysis is thereby a standard approach in structural biology. For intrinsically disordered or denatured proteins furthermore, secondary chemical shifts reveal the propensity of particular segments to form different secondary structures. However, because the atoms in unfolded proteins all have very similar chemical environments, the chemical shifts measured for a certain atom type vary less than in globular proteins. Since chemical shifts can be measured precisely, the secondary chemical shifts calculated for an unfolded system depend mainly on the particular random coil chemical shift database chosen as a point of reference. Certain databases correct the random coil shift for a given residue based on its neighbors in the amino acid sequence. However, these corrections are typically derived from the analysis of model peptides; there have been relatively few direct and systematic studies of the effect of neighboring residues for specific amino acid sequences in disordered proteins. For the study reported here, we used the intrinsically disordered C-terminal domain of TDP-43, which has a highly repetitive amino-acid sequence, as a model system. We assigned the chemical shifts of this protein at low pH in urea. Our results demonstrate that the identity of the nearest neighbors is decisive in determining the value of the chemical shift for atoms in a random coil arrangement. Based on these observations, we also outline a possible approach to construct a random-coil library of chemical shifts that comprises all possible arrangement of tripeptides from a manageable number of polypeptides. PMID- 27653630 TI - Functions of Type II Thioesterases in Bacterial Polyketide Biosynthesis. AB - Many polyketides show biological activities and have thus been applied in clinics, as food additives, and in agriculture. Type II thioesterases (TEIIs) play an important role in polyketide biosynthesis. Most TEIIs belong to alpha/beta-hydrolase family and usually contain a catalytic triad Ser-His-Asp. In polyketide biosynthesis, TEIIs can play an editing role by removal of aberrant non-extendable acyl units in elongation steps, a starter unit selection role by removal of unfavored starter acyl units in initiation steps, and a releasing role by removal of final product in termination steps. Complementation of TEIIs has been observed and applied. PMID- 27653631 TI - Transition of Solvent Interaction Research from Basic Science to Applied Science. AB - As a graduate course student, I studied the aggregation behavior of the wheat protein gluten, induced by changes in pH and ionic strength, thus beginning my research career in the field of solvent effects. The following 5 years were spent as a post-doctoral reseracher in the U.S., focused on protein-solvent interactions, which, according to my advisor, Dr. Timasheff, was too basic to be supported by academic grants. This study, however, answered a number of questions about how different solvents affect behavior of proteins in solution, e.g., a solubility behavior known as Hofmeister series. This research experience landed me an R&D position at a startup biotech company, Amgen, where knowledge on solvents played a fundamental role in protein refolding, formulation and chromatography. This demonstrates the unanticipated possibility that an un funded, basic academic science study earlier can be transitioned later into an industrially-significant applied science. PMID- 27653632 TI - The effect of brisk walking on postural stability, bone mineral density, body weight and composition in women over 50 years with a sedentary occupation: a randomized controlled trial. AB - BACKGROUND: To assess the effect of brisk walking on postural stability, bone mineral density (BMD) and body composition in women over 50 years of age with a sedentary occupation. METHODS: A 10-week walking intervention based on self regulated brisk walking (BW) to or from work of 30-35 min at least 5 times per week. The research included a total of 104 women (58 women in intervention group). The mean center of pressure (COP) velocity in medial-lateral and anterior posterior directions, mean total COP velocity with eyes open and closed, BMD of the distal forearm and the calcaneus, body weight, fat mass, and lean body mass were assessed. RESULTS: The BW intervention was completed by 76 % of participants. A significant effect (time * group interaction) was confirmed only in the mean COP velocity in the anterior-posterior direction with eyes closed (F = 7.41, P = 0.008). The effect of BW was not confirmed in BMD, body weight, or body composition. The results indicate that the effect of the intervention is influenced by baseline body mass index in body weight, fat mass and visceral adipose tissue. CONCLUSIONS: BW prevents the deterioration of postural stability with eyes closed, which can have a direct effect on reducing the risk of falls under worse spatial orientation and visibility. The presented intervention model is insufficient for weight loss, changes in BMD, or body composition, and its effect should be assessed during a longer period of time. TRIAL REGISTRATION: German Clinical Trials Register DRKS00007638 , registered March 10, 2015 (retrospectively registered). PMID- 27653633 TI - Erratum to: Maternally-derived antibodies do not prevent transmission of swine influenza A virus between pigs. PMID- 27653634 TI - A Convenient Late-Stage Fluorination of Pyridylic C-H Bonds with N Fluorobenzenesulfonimide. AB - Pyridine features prominently in pharmaceuticals and drug leads, and methods to selectively manipulate pyridine basicity or metabolic stability are highly sought after. A robust, metal-free direct fluorination of unactivated pyridylic C-H bonds was developed. This convenient reaction shows high functional-group tolerance and offers complimentary selectivity to existing C-H fluorination strategies. Importantly, this late-stage pyridylic C-H fluorination provides opportunities to rationally modulate the basicity, lipophilicity, and metabolic stability of alkylpyridine drugs. PMID- 27653635 TI - Elevational Distribution and Ecology of Small Mammals on Tanzania's Second Highest Mountain. AB - Mt. Meru is Tanzania's second highest mountain and the ninth highest in Africa. The distribution and abundance of small mammals on this massif are poorly known. Here we document the distribution of shrews and rodents along an elevational gradient on the southeastern versant of Mt. Meru. Five sites were sampled with elevational center points of 1950, 2300, 2650, 3000, and 3600 m, using a systematic methodology of standard traps and pitfall lines, to inventory the shrews and rodents of the slope. Ten species of mammal were recorded, comprising 2 shrew and 8 rodent species with the greatest diversity for each group at 2300 m. No species previously unrecorded on Mt. Meru was observed. Two rodent genera that occur in nearby Eastern Arc Mountains (Hylomyscus and Beamys) were not recorded. The rodent Lophuromys verhageni and a recently described species of shrew, Crocidura newmarki, are the only endemic mammals on Mt. Meru, and were widespread across the elevational gradient. As in similar small mammal surveys on other mountains of Tanzania, rainfall positively influenced trap success rates for shrews, but not for rodents. This study provides new information on the local small mammal fauna of the massif, but numerous other questions remain to be explored. Comparisons are made to similar surveys of other mountains in Tanzania. PMID- 27653636 TI - Dystonia in ATP2B3-associated X-linked spinocerebellar ataxia. PMID- 27653637 TI - Nursing care in multifunctional small group homes providing day, visiting and overnight services for older people living at home. AB - Home care programs for older people have been developed around the world. Nurses are key to these programs. The aim of this study is to explore details of the nursing activities used in group homes to provide a basis for describing effective nursing practices in such facilities. A self-administered questionnaire was sent to 240 randomly selected facilities throughout Japan in 2013. Responses indicated that the activities of nurses in managing the health of older people included determining the need for medical consultations, dealing with emergencies, and making arrangements for the use of flexible care services. Nursing activities were directly related to the percentage of older people in each facility with diagnoses such as dementia or heart disease. Nurses reported low general self-efficacy for some of the more specialized nursing activities they performed. Nursing activities are performed with the aim of supporting older people with high health care needs to continue living at home; are tailored to the characteristics of residents and contribute to the provision of timely health examinations and flexible arrangement of services. Findings indicate that it might be advantageous to increase the nursing staffing at these facilities, to provide care guidelines and training opportunities to increase nurse self efficacy. PMID- 27653638 TI - Patterns of behaviour in families of critically ill patients in the emergency room: a focused ethnography. AB - AIM: The aim of this study was to understand the patterns of behaviour from relatives of critically ill patients admitted to the emergency room. BACKGROUND: Admission of a critically ill family member to an accident and emergency department is often a sudden and unexpected experience for the family. This stressful event often creates feelings of instability and intense suffering in relatives. Understanding the experiences of these families is essential for the provision of comprehensive health care in the emergency room. DESIGN: A focused ethnography design was applied to the study. METHODS: Peripheral participant observation and informal conversations were conducted in an emergency room in southern Brazil during January 2015. Analysis of data was based on Leininger. FINDINGS: Suffering was recurrent among family members of critically ill patients admitted to the emergency room. The environment, which was conditioned by the patient's life-threatening situation and professionals' attitudes, resulted in relatives experiencing a range of feelings from suffering to calm. A distant approach and poor communication of professionals made relatives confused and silent. Factors that seemed to foster feelings of calm in families were the establishment of a continuous and close communication with professionals and the possibility to remain with the patient outside the established visiting hours. CONCLUSION: The findings of this study challenge emergency department providers and managers to promote comprehensive care in the emergency room by inviting family members to be with the patient and by engaging in family-centred care. PMID- 27653639 TI - Is There a Difference in Tachycardia Cycle Length during SVT in Children with AVRT and AVNRT? AB - BACKGROUND: There are limited adult data suggesting the tachycardia cycle length (TCL) of atrioventricular reentry tachycardia (AVRT) is shorter than atrioventricular nodal reentry tachycardia (AVNRT), though little data exist in children. We sought to determine if there is a difference in TCL between AVRT and AVNRT in children. METHODS: A single-center retrospective review of children with supraventricular tachycardia (SVT) from 2000 to 2015 was performed. INCLUSION CRITERIA: Age <= 18 years, invasive electrophysiology study (EPS) confirming AVRT or AVNRT. EXCLUSION CRITERIA: Atypical AVNRT, congenital heart disease, antiarrhythmic medication use at time of EPS. Data were compared between patients with AVRT and AVNRT via t-test, chi2 test, and linear regression. RESULTS: A total of 835 patients were included (12 +/- 4 years, 52 +/- 31 kg, TCL 321 +/- 55 ms), 539 (65%) with AVRT (270 Wolff-Parkinson-White, 269 concealed pathways) and 296 (35%) with AVNRT. Patients with AVRT were younger (11.7 +/- 4.1 years vs 13.0 +/- 3.6 years, P < 0.001) and smaller (49 +/- 22 kg vs 57 +/- 43 kg, P < 0.001). In the baseline state, the TCL was shorter in AVRT than AVRNT (329 +/- 51 ms vs 340 +/- 60 ms, P = 0.04). In patients requiring isoproterenol to induce SVT, there was no difference in TCL (290 +/- 49 ms vs 297 +/- 49 ms, P = 0.26). When controlling for age, there was no difference in TCL between AVRT and AVNRT at baseline or on isoproterenol. The regression equation for TCL in the baseline state was TCL = 290 + 4 (age), indicating the TCL will increase by 4 ms above a baseline of 290 ms for each year of life. CONCLUSIONS: When controlling for age, there is no difference in the TCL between AVRT and AVNRT in children. Age, not tachycardia mechanism, is the most significant factor in predicting TCL. PMID- 27653640 TI - Culture of Tumorigenic Cells on Protein Fibers Reveals Metastatic Cell Behaviors. AB - Tumorigenic cell behaviors can be suppressed or enhanced by their physicochemical environment. As a first step toward developing materials that allow tumorigenic behaviors to be observed and manipulated, we cultured related MCF10 breast cell lines on fibers composed of the Drosophila protein Ultrabithorax (Ubx). These cell lines, originally derived from fibrocystic breast tissue, represent a continuum of tumorigenic behavior. Immortal but nontumorigenic MCF10A cells, as well as semitumorigenic MCF10AT cells, attached and spread on Ubx fibers. MCF10CA 1a cells, the most highly transformed line, secreted high concentrations of matrix metalloproteinases when cultured on Ubx materials, resulting in differences in cell attachment and cytoskeletal structure, and enabling invasive behavior. Because the mechanical and functional properties of Ubx fibers can be genetically manipulated, these materials provide a valuable tool for cancer research, allowing creation of diverse microenvironments that allow assessment of invasive, metastatic behavior. PMID- 27653642 TI - Wrist-independent energy expenditure prediction models from raw accelerometer data. AB - PURPOSES: (1) Develop artificial neural network (ANN) models for wrist accelerometer data which can predict energy expenditure (EE) using data collected from either wrist. (2) Develop ANNs for detecting the wrist on which the accelerometer was worn. Forty-four adults wore GENEActiv accelerometers on the left and right wrists and a portable metabolic analyzer while participating in a 90 min semi-structured activity protocol. Participants performed 14 sedentary, lifestyle, exercise, and ambulatory activities and were allowed to choose activity order, duration, and intensity. ANNs were created to predict EE and wrist detection using a leave-one-out cross-validation. In total, 12 combinations of feature sets (mean and variance of raw, vector magnitude, and absolute value data), training methods (left- and right- wrist), and testing methods (left- and right-wrist data) were used to develop EE prediction ANNs. Accuracy of the ANNs was evaluated using correlations, root mean square error (RMSE), and bias, using metabolic analyzer data as the criterion for EE. ANNs using raw data from the same wrist (e.g. EE predicted from right wrist ANNs using accelerometer data from right wrist) had the highest accuracy for EE prediction (r = 0.84, RMSE = 1.25-1.26 METs); conversely, opposite-wrist prediction accuracy (e.g. EE predicted from right wrist ANNs using accelerometer data from left wrist) was lower (r = 0.60-0.64, RMSE = 1.93-2.01 METs). Preprocessing into absolute values prior to ANN development allowed for, high EE prediction accuracy, with no difference in accuracy for same- versus opposite-wrist prediction (r = 0.80 0.83, RMSE = 1.30-1.49 METs). Wrist detection ANNs correctly determined wrist placement 100% of the time. Highly accurate, wrist-independent EE prediction ANNs were developed by computing absolute values of raw acceleration data prior to ANN development. This method provides a potential approach for advancing predictive accuracy of wrist-worn accelerometers. PMID- 27653641 TI - Eurobarometer survey and e-cigarettes: unsubstantiated claims. PMID- 27653645 TI - Staff cuts: there is an alternative. AB - As you read this, another RCN Emergency Care Association (ECA) conference will have ended and participants will have been energised for another year. It is always a pleasure to meet people for whom emergency care is a genuine passion, not simply a job. PMID- 27653644 TI - Essential oil composition of Ajuga comata Stapf. from Southern Zagros, Iran. AB - The chemical composition of essential oil obtained from the aerial parts of Ajuga comata Stapf. was analyzed by GC and GC/MS. Thirty-seven components were identified in the oil. (E)-beta-caryophyllene (30.9%), caryophyllene oxide (24.9%), (E)-beta-farnesene (12.6%), beta-eudesmol (3.2%), delta-cadinene (3.1%) and germacrene D (3.0%) were the main compounds in the EOs. The chemical composition of A. comata Stapf. from the Southern Zagros of Iran is reported for the first time. PMID- 27653648 TI - Changes to guidelines on resuscitation and advanced life support. AB - RESUSCITATION GUIDELINES that place greater emphasis on chest compressions in cardiopulmonary resuscitation (CPR) and the use of automated external defibrillators have been published. PMID- 27653649 TI - Driven to distraction. AB - A drive to raise funds for a 3D sensory pain distraction system for children in the emergency department (ED) at James Cook University Hospital, Middlesbrough, has been launched by a local shopping centre. About 20,000 children present at the ED every year. PMID- 27653646 TI - Donor scheme launched to meet demand for organs in Scotland. AB - A CAMPAIGN to encourage people to sign up to the organ-donor register has been launched in Scotland. PMID- 27653650 TI - Waiting around. AB - After reading the article by Julian Newell (Emergency Nurse 18, 6, 8), I had to smile. Discussing the abolition of the four-hour emergency department (ED) standard, he says: 'We may see the return to the days of patients lying on trolleys for hours as they wait for a bed to become available.' PMID- 27653651 TI - Coping with death. AB - Benjamin Franklin said that 'in this world nothing can be said to be certain, except death and taxes'. Death is something that nurses, particularly those working in emergency departments, have to deal with sometimes on a daily basis, as most serious accidents and emergencies can result in loss of life. PMID- 27653652 TI - Numeracy in nursing and healthcare: calculations and practice Pearl Shihab Numeracy in nursing and healthcare: calculations and practice Pearson Education L17.99 248pp 9780273720744 0273720740 [Formula: see text]. AB - THE AUTHOR of this well-written book explains the calculations nurses must make, from the basic to the most complicated. PMID- 27653653 TI - Law and Professional Issues in Nursing Richard Griffith Law and Professional Issues in Nursing Cassam Tengnah Learning Matters L20 248pp 9781844453726 1844453723 [Formula: see text]. AB - LEGAL ISSUES concerning essential nursing care are demystified in this useful book, which covers accountability, equality and human rights, consent to treatment, confidentiality, and the protection of vulnerable clients including children. PMID- 27653654 TI - Clinical Teaching Made Easy Judy McKimm , Tim Swanwick Clinical Teaching Made Easy Quay Books L22.99 250pp 9781856424081 [Formula: see text]. AB - THIS EASY-TO-USE reference guide offers a broad overview of medical education, including the importance of curriculum design and quality assurance. PMID- 27653655 TI - Diary. AB - Our roundup of what's on. PMID- 27653657 TI - Diagnosing the cause of blackouts. AB - About half of the UK population will experience blackouts, or transient loss of consciousness (TLoC), at some point in their lives, and some will attend emergency departments as a result, according to the National Institute for Health and Clinical Excellence (NICE). PMID- 27653656 TI - Notice board. AB - Courses, events, grants, and awards to progress your career. PMID- 27653658 TI - Patient group directions. AB - The patient group directions (PGD) website, which is part of the National electronic Library for Medicines (NeLM), is the national resource in England for healthcare professionals who work with, or who are involved in the development or review of, PGDs. PMID- 27653659 TI - Safeguarding website. AB - Safeguarding is part of everyday nursing practice in all settings and, according to the Nursing and Midwifery Council (NMC), nurses should have the skills to confidently recognise and effectively manage situations where they suspect people in their care are at risk of harm, abuse or neglect, including poor practice. PMID- 27653660 TI - Policies and practice. AB - NHS Evidence, a website that allows all health and social care workers to access a wide range of information on quality patient care, has a dedicated emergency and urgent care section that provides high quality and up-to-date information and resources on all aspects of emergency and urgent health care, including clinical and organisational issues. PMID- 27653661 TI - Relationship between cardio-ankle vascular index and homocysteine in hypertension subjects with hyperhomocysteinemia. AB - BACKGROUND: Arteriosclerosis evaluated by arterial stiffness is the basic pathophysiological change during the development of hypertension. Cardio-ankle vascular index (CAVI) is an index of arterial stiffness. Hyperhomocysteinemia (HHcy) is an independent risk factor for vascular diseases. However, there was little research about the relationship between CAVI and homocysteine (Hcy) in hypertension subjects with HHcy. METHODS: A total of 330 subjects (M/F 133/197) from Vascular Medicine of Peking University Shougang Hospital were divided into four groups: control group (group 1, normotensive with normal Hcy, n = 149), hypertension group (group 2, n = 113), HHcy group (group 3, n = 30), and hypertension with HHcy group (group 4, n = 38). CAVI was measured by VS-1000 apparatus. RESULTS: Our results showed that CAVI was significantly higher in group 4 than in group 1 and group 2 (8.41 +/- 1.08 vs. 7.79 +/- 1.14; 8.41 +/- 1.08 vs. 7.87 +/- 1.02, both p < 0.05, respectively). Positive correlation between CAVI and Hcy was found in the entire study group (r = 0.109, p = 0.049) and hypertension subjects (group 2 + group 4; r = 0.202, p = 0.014). Multivariate analysis showed that Hcy was an independent associating factor of CAVI in all subjects (beta = 0.251, p = 0.034). CONCLUSIONS: The present study showed that CAVI was significantly higher in hypertension subjects with HHcy compared to hypertension group. There was significant correlation between CAVI and Hcy, indicating the relationship between arterial stiffness and biomarkers in vascular related diseases. PMID- 27653662 TI - Cutaneous Gamma-Delta T-Cell Lymphoma Successfully Treated With Brentuximab Vedotin. PMID- 27653663 TI - A computational lens for sexual-stage transmission, reproduction, fitness and kinetics in Plasmodium falciparum. AB - BACKGROUND: The burden of falciparum malaria remains unacceptably high in much of sub-Saharan Africa and massive efforts are underway to eliminate the parasite. While symptoms of malaria are caused by asexual reproduction of the parasite, transmission to new human hosts relies entirely on male and female sexual-stage parasites, known as gametocytes. Successful transmission can be observed at very low gametocyte densities, which raises the question of whether transmission enhancing mechanisms exist in the human host, the mosquito, or both. METHODS: A new computational model was developed to investigate the probability of fertilization over a range of overdispersion parameters and male gamete exploration rates. Simulations were used to fit a likelihood surface for data on rates of mosquito infection across a wide range of host gametocyte densities. RESULTS: The best fit simultaneously requires very strong overdispersion and faster gamete exploration than is possible with random swimming in order to explain typical prevalence levels in mosquitoes. Gametocyte overdispersion or clustering in the human host and faster gamete exploration of the mosquito blood meal are highly probably given these results. CONCLUSIONS: Density-dependent gametocyte clustering in the human host, and non-random searching (e.g., chemotaxis) in the mosquito are probable. Future work should aim to discover these mechanisms, as disrupting parasite development in the mosquito will play a critical role in eliminating malaria. PMID- 27653664 TI - Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries. AB - We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD. PMID- 27653666 TI - Genome-wide analysis of Dof transcription factors reveals functional characteristics during development and response to biotic stresses in pepper. AB - The DNA-binding with one zinc finger proteins (Dofs) are a plant-specific family of transcription factors. The Dofs are involved in a variety of biological processes such as phytohormone production, seed development, and environmental adaptation. Dofs have been previously identified in several plants, but not in pepper. We identified 33 putative Dof genes in pepper (CaDofs). To gain an overview of the CaDofs, we analyzed phylogenetic relationships, protein motifs, and evolutionary history. We divided the 33 CaDofs, containing 25 motifs, into four major groups distributed on eight chromosomes. We discovered an expansion of the CaDofs dated to a recent duplication event. Segmental duplication that occurred before the speciation of the Solanaceae lineages was predominant among the CaDofs. The global gene-expression profiling of the CaDofs by RNA-seq analysis showed distinct temporal and pathogen-specific variation during development and response to biotic stresses (two TMV strains, PepMoV, and Phytophthora capsici), suggesting functional diversity among the CaDofs. These results will provide the useful clues into the responses of Dofs in biotic stresses and promote a better understanding of their multiple function in pepper and other species. PMID- 27653667 TI - Intein mediated hyper-production of authentic human basic fibroblast growth factor in Escherichia coli. AB - Human basic fibroblast growth factor is a functionally versatile but very expensive polypeptide. In this communication, employing a novel amplification method for the target gene and genetic optimization of a previously engineered expression construct, pWK3R, together with a refined fed-batch fermentation protocol, we report an achievement of a phenomenal yield of 610 mg/L of the 146 aa authentic human basic fibroblast growth factor (bFGF) in Escherichia coli. Construct pWK3R was first modified to form plasmid pWK311ROmpAd, which was devoid of the ompA leader sequence and possessed two copies of a DNA segment encoding a fusion product comprising an intein, Saccharomyces cerevisiae vascular membrane ATPase (VMA), and bFGF. When E. coli transformant JM101 [pWK311ROmpAd] was cultivated using the refined fed-batch fermentation protocol, superb expression resulting in a total yield of 610 mg/L of bFGF was detected. Despite existing in high levels, the bFGF remained to be soluble and highly bioactive. PMID- 27653665 TI - T-type calcium channels in synaptic plasticity. AB - The role of T-type calcium currents is rarely considered in the extensive literature covering the mechanisms of long-term synaptic plasticity. This situation reflects the lack of suitable T-type channel antagonists that till recently has hampered investigations of the functional roles of these channels. However, with the development of new pharmacological and genetic tools, a clear involvement of T-type channels in synaptic plasticity is starting to emerge. Here, we review a number of studies showing that T-type channels participate to numerous homo- and hetero-synaptic plasticity mechanisms that involve different molecular partners and both pre- and post-synaptic modifications. The existence of T-channel dependent and independent plasticity at the same synapse strongly suggests a subcellular localization of these channels and their partners that allows specific interactions. Moreover, we illustrate the functional importance of T-channel dependent synaptic plasticity in neocortex and thalamus. PMID- 27653668 TI - Inhibition in task switching: The reliability of the n - 2 repetition cost. AB - The n - 2 repetition cost seen in task switching is the effect of slower response times performing a recently completed task (e.g. an ABA sequence) compared to performing a task that was not recently completed (e.g. a CBA sequence). This cost is thought to reflect cognitive inhibition of task representations and as such, the n - 2 repetition cost has begun to be used as an assessment of individual differences in inhibitory control; however, the reliability of this measure has not been investigated in a systematic manner. The current study addressed this important issue. Seventy-two participants performed three task switching paradigms; participants were also assessed on rumination traits and processing speed-measures of individual differences potentially modulating the n 2 repetition cost. We found significant n - 2 repetition costs for each paradigm. However, split-half reliability tests revealed that this cost was not reliable at the individual-difference level. Neither rumination tendencies nor processing speed predicted this cost. We conclude that the n - 2 repetition cost is not reliable as a measure of individual differences in inhibitory control. PMID- 27653669 TI - The nuclear genome of Rhazya stricta and the evolution of alkaloid diversity in a medically relevant clade of Apocynaceae. AB - Alkaloid accumulation in plants is activated in response to stress, is limited in distribution and specific alkaloid repertoires are variable across taxa. Rauvolfioideae (Apocynaceae, Gentianales) represents a major center of structural expansion in the monoterpenoid indole alkaloids (MIAs) yielding thousands of unique molecules including highly valuable chemotherapeutics. The paucity of genome-level data for Apocynaceae precludes a deeper understanding of MIA pathway evolution hindering the elucidation of remaining pathway enzymes and the improvement of MIA availability in planta or in vitro. We sequenced the nuclear genome of Rhazya stricta (Apocynaceae, Rauvolfioideae) and present this high quality assembly in comparison with that of coffee (Rubiaceae, Coffea canephora, Gentianales) and others to investigate the evolution of genome-scale features. The annotated Rhazya genome was used to develop the community resource, RhaCyc, a metabolic pathway database. Gene family trees were constructed to identify homologs of MIA pathway genes and to examine their evolutionary history. We found that, unlike Coffea, the Rhazya lineage has experienced many structural rearrangements. Gene tree analyses suggest recent, lineage-specific expansion and diversification among homologs encoding MIA pathway genes in Gentianales and provide candidate sequences with the potential to close gaps in characterized pathways and support prospecting for new MIA production avenues. PMID- 27653670 TI - Effects of structured testing versus routine testing of blood glucose in diabetes self-management: A randomized controlled trial. AB - AIMS: To compare the effects of structured and routine testing regimens used in self-monitoring of blood glucose (SMBG) on glycemic control and diabetes self management in insulin-naive type 2 diabetes patients. METHODS: Sixty-two outpatients with insulin-naive type 2 diabetes were randomly allocated into two less-frequent SMBG usage groups: a structured testing group (STG) and a routine testing group (RTG). Subjects in STG measured 7-points on SMBG for 3 consecutive days once every two months without daily testing; subjects in RTG measured SMBG 3 times each week before breakfast on Monday and Friday and before dinner on Wednesday. The primary endpoint was HbA1c reduction. The secondary endpoints were change in body weight, blood pressure, treatment change, and self-management performance change. RESULTS: HbA1c levels were significantly decreased by 0.32% (3.50mmol/mol) in STG, partly because physicians changed medications more actively. In contrast, body weight and systolic/diastolic blood pressure were significantly reduced by 0.94kg and 6.8/4.7mmHg, respectively, in RTG, possibly related to the increased diet and exercise score in RTG. CONCLUSIONS: Structured testing without daily testing is beneficial for glycemic control; routine testing 3 times a week is more helpful for daily self-management. In low SMBG frequency usage, these two regimens can be utilized according to individual diabetic conditions. PMID- 27653671 TI - Unusual lattice vibration characteristics in whiskers of the pseudo-one dimensional titanium trisulfide TiS3. AB - Transition metal trichalcogenides form a class of layered materials with strong in-plane anisotropy. For example, titanium trisulfide (TiS3) whiskers are made out of weakly interacting TiS3 layers, where each layer is made of weakly interacting quasi-one-dimensional chains extending along the b axis. Here we establish the unusual vibrational properties of TiS3 both experimentally and theoretically. Unlike other two-dimensional systems, the Raman active peaks of TiS3 have only out-of-plane vibrational modes, and interestingly some of these vibrations involve unique rigid-chain vibrations and S-S molecular oscillations. High-pressure Raman studies further reveal that the AgS-S S-S molecular mode has an unconventional negative pressure dependence, whereas other peaks stiffen as anticipated. Various vibrational modes are doubly degenerate at ambient pressure, but the degeneracy is lifted at high pressures. These results establish the unusual vibrational properties of TiS3 with strong in-plane anisotropy, and may have relevance to understanding of vibrational properties in other anisotropic two-dimensional material systems. PMID- 27653672 TI - Low-dose radiation differentially regulates protein acetylation and histone deacetylase expression in human coronary artery endothelial cells. AB - PURPOSE: Ionizing radiation induces cardiovascular disease, the endothelium being the main target. The exact mechanism of the damage is unclear but the involvement of multiple signaling pathways is probable. Reversible lysine acetylation is a posttranslational protein modification that regulates activity across a broad range of signaling pathways. The aim of this study was to determine if a low radiation dose results in acetylome alteration in endothelial cells. MATERIALS AND METHODS: Human coronary artery endothelial cell line was irradiated with Cs 137 gamma-rays (0.5 Gy) and proteomics analysis was performed using enriched acetylated peptides and all peptides. Data were validated using immunoblotting, deacetylase activity assay, and RhoA activity assay. RESULTS: Nearly a hundred proteins were found to have an altered acetylation status 24 h after irradiation, primarily due to an overall decrease in acetylation. The expression of specific deacetylases was significantly increased, coinciding with an enhancement in global deacetylase activity. Proteins changed in their acetylation status belonged to several pathways including protein synthesis, cytoskeleton-related processes, protein folding and calcium signaling. The predicted changes in the RhoA/actin cytoskeleton pathway were validated by immunoassay. CONCLUSIONS: This study shows that protein acetylation is an important mediator of radiation responses in human cardiac coronary endothelial cells. Increased knowledge of the endothelial response to radiation is crucial for the development of normal tissue sparing modalities during radiation therapy. PMID- 27653674 TI - Use of Visible and Short-Wave Near-Infrared Hyperspectral Imaging To Fingerprint Anthocyanins in Intact Grape Berries. AB - In red grape berries, anthocyanins account for about 50% of the skin phenols and are responsible for the final wine color. Individual anthocyanin levels and compositional profiles vary with cultivar, maturity, season, region, and yield and have been proposed as chemical markers to differentiate wines and to provide valuable information regarding the adulteration of musts and wines. A fast, easy, solvent-free, nondestructive method based on visible, short-wave, and near infrared hyperspectral imaging (HSI) in intact grape berries to fingerprint the color pigments in eight different grape varieties was developed and tested against HPLC. Predictive models based on modified partial least-squares (MPLS) were built for 14 individual anthocyanins with coefficients of determination of cross-validation (R2CV) ranging from 0.70 to 0.93. For the grouping of total and nonacylated anthocyanins, external validation was conducted with coefficient of determination of prediction (R2P) of 0.86. HSI could potentially become an alternative to HPLC with reduced analysis time and labor costs while providing reliable and robust information on the anthocyanin composition of grape berries. PMID- 27653673 TI - Comparison of oblique coronal images in knee of three-dimensional isotropic T2 weighted turbo spin echo MRI versus two-dimensional fast spin echo T2-weighted sequences for evaluation of posterior cruciate ligament injury. AB - OBJECTIVE: To compare image quality between three-dimensional volume isotropic turbo spin echo acquisition (3D VISTA) with the posterior cruciate ligament (PCL) view and two-dimensional (2D) fast spin echo (FSE) for evaluation of PCL injury. METHODS: This retrospective study included 60 patients with clinical suspicion of PCL injury who underwent both 2D FSE and 3D VISTA of the knee between January 2015 and December 2015. The diagnostic performance of each oblique coronal view and the combined images was evaluated for sensitivity, specificity and accuracy for diagnosing a PCL tear. The arthroscopically confirmed diagnoses were used as the reference standard. Data were analyzed using the McNemar test. RESULTS: The mean contrast-to-noise ratio was significantly higher for 3D VISTA than for 2D FSE. The two imaging modalities did not differ significantly in anatomical identification ability, with the exception of margin sharpness, which was inferior for 3D VISTA with Reader 2 (p = 0.038). When we classified the diagnoses of PCL injury as normal or abnormal, there were no significant differences in sensitivity, specificity or accuracy between the PCL view of 3D VISTA and 2D FSE images (p > 0.05). CONCLUSION: 3D VISTA had a superior contrast-to-noise ratio than 2D FSE and similar image quality in the evaluation of the PCL. The PCL view of 3D VISTA has the same diagnostic ability as 2D FSE in the diagnosis of PCL injury and can thus replace 2D FSE. Advances in knowledge: The oblique coronal view 3D VISTA MRI has similar diagnostic ability to 2D FSE in the diagnosis of PCL injury, and therefore 3D VISTA image can replace 2D FSE. PMID- 27653675 TI - COOLAIR Antisense RNAs Form Evolutionarily Conserved Elaborate Secondary Structures. AB - There is considerable debate about the functionality of long non-coding RNAs (lncRNAs). Lack of sequence conservation has been used to argue against functional relevance. We investigated antisense lncRNAs, called COOLAIR, at the A. thaliana FLC locus and experimentally determined their secondary structure. The major COOLAIR variants are highly structured, organized by exon. The distally polyadenylated transcript has a complex multi-domain structure, altered by a single non-coding SNP defining a functionally distinct A. thaliana FLC haplotype. The A. thaliana COOLAIR secondary structure was used to predict COOLAIR exons in evolutionarily divergent Brassicaceae species. These predictions were validated through chemical probing and cloning. Despite the relatively low nucleotide sequence identity, the structures, including multi-helix junctions, show remarkable evolutionary conservation. In a number of places, the structure is conserved through covariation of a non-contiguous DNA sequence. This structural conservation supports a functional role for COOLAIR transcripts rather than, or in addition to, antisense transcription. PMID- 27653676 TI - The Ribosome Cooperates with the Assembly Chaperone pICln to Initiate Formation of snRNPs. AB - The formation of macromolecular complexes within the crowded environment of cells often requires aid from assembly chaperones. PRMT5 and SMN complexes mediate this task for the assembly of the common core of pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs). Core formation is initiated by the PRMT5 complex subunit pICln, which pre-arranges the core proteins into spatial positions occupied in the assembled snRNP. The SMN complex then accepts these pICln-bound proteins and unites them with small nuclear RNA (snRNA). Here, we have analyzed how newly synthesized snRNP proteins are channeled into the assembly pathway to evade mis-assembly. We show that they initially remain bound to the ribosome near the polypeptide exit tunnel and dissociate upon association with pICln. Coincident with its release activity, pICln ensures the formation of cognate heterooligomers and their chaperoned guidance into the assembly pathway. Our study identifies the ribosomal quality control hub as a site where chaperone mediated assembly of macromolecular complexes can be initiated. PMID- 27653677 TI - Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5 UFM1 Complex. AB - Modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is a critical cellular process implicated in a variety of cellular states and outcomes. A prerequisite for target protein modification by a UBL is the activation of the latter by activating enzymes (E1s). Here, we present the crystal structure of the non-canonical homodimeric E1, UBA5, in complex with its cognate UBL, UFM1, and supporting biochemical experiments. We find that UBA5 binds to UFM1 via a trans-binding mechanism in which UFM1 interacts with distinct sites in both subunits of the UBA5 dimer. This binding mechanism requires a region C-terminal to the adenylation domain that brings UFM1 to the active site of the adjacent UBA5 subunit. We also find that transfer of UFM1 from UBA5 to the E2, UFC1, occurs via a trans mechanism, thereby requiring a homodimer of UBA5. These findings explicitly elucidate the role of UBA5 dimerization in UFM1 activation. PMID- 27653678 TI - IFN-gamma Induces Histone 3 Lysine 27 Trimethylation in a Small Subset of Promoters to Stably Silence Gene Expression in Human Macrophages. AB - The mechanisms by which IFN-gamma activates expression of interferon-stimulated genes that have inflammatory and host defense functions are well understood. In contrast, little is known about how IFN-gamma represses gene expression. By using transcriptomic and epigenomic analysis, we found that stable repression of a small group of genes by IFN-gamma is associated with recruitment of the histone methyltransferase EZH2 and deposition of the negative mark histone 3 lysine 27 trimethylation (H3K27me3) at their promoters. Repressed genes included MERTK, PPARG, and RANK, which have anti-inflammatory functions and promote osteoclast differentiation. Gene repression and H3K27me3 persisted after IFN-gamma signaling was terminated, and these silenced genes were no longer responsive to glucocorticoids, IL-4, and M-CSF. These results identify cytokine-induced H3K27 trimethylation as a mechanism that stabilizes gene silencing in macrophages. IFN gamma-induced macrophage activation is thus reinforced by a chromatin-based mechanism that blocks anti-inflammatory and opposing pathways. PMID- 27653679 TI - The Role of Dendritic Cells in S. pneumoniae Transport to Follicular Dendritic Cells. AB - Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells. PMID- 27653680 TI - Reprogramming by De-bookmarking the Somatic Transcriptional Program through Targeting of BET Bromodomains. AB - One critical event in reprogramming to pluripotency is erasure of the somatic transcriptional program of starting cells. Here, we present the proof of principle of a strategy for reprogramming to pluripotency facilitated by small molecules that interfere with the somatic transcriptional memory. We show that mild chemical targeting of the acetyllysine-binding pockets of the BET bromodomains, the transcriptional bookmarking domains, robustly enhances reprogramming. Furthermore, we show that chemical targeting of the transcriptional bookmarking BET bromodomains downregulates or turns off the expression of somatic genes in both naive and reprogramming fibroblasts. Chemical blocking of the BET bromodomains also results in loss of fibroblast morphology early in reprogramming. We therefore experimentally demonstrate that cell fate conversion can be achieved by chemically targeting the transcriptional bookmarking BET bromodomains responsible for transcriptional memory. PMID- 27653682 TI - Increased Persistent Sodium Current Causes Neuronal Hyperexcitability in the Entorhinal Cortex of Fmr1 Knockout Mice. AB - Altered neuronal excitability is one of the hallmarks of fragile X syndrome (FXS), but the mechanisms underlying this critical neuronal dysfunction are poorly understood. Here, we find that pyramidal cells in the entorhinal cortex of Fmr1 KO mice, an established FXS mouse model, display a decreased AP threshold and increased neuronal excitability. The AP threshold changes in Fmr1 KO mice are caused by increased persistent sodium current (INaP). Our results indicate that this abnormal INaP in Fmr1 KO animals is mediated by increased mGluR5-PLC-PKC (metabotropic glutamate receptor 5/phospholipase C/protein kinase C) signaling. These findings identify Na(+) channel dysregulation as a major cause of neuronal hyperexcitability in cortical FXS neurons and uncover a mechanism by which abnormal mGluR5 signaling causes neuronal hyperexcitability in a FXS mouse model. PMID- 27653681 TI - Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation. AB - Cancer genomics has provided an unprecedented opportunity for understanding genetic causes of human cancer. However, distinguishing which mutations are functionally relevant to cancer pathogenesis remains a major challenge. We describe here a mammary stem cell (MaSC) organoid-based approach for rapid generation of somatic genetically engineered mouse models (GEMMs). By using RNAi and CRISPR-mediated genome engineering in MaSC-GEMMs, we have discovered that inactivation of Ptpn22 or Mll3, two genes mutated in human breast cancer, greatly accelerated PI3K-driven mammary tumorigenesis. Using these tumor models, we have also identified genetic alterations promoting tumor metastasis and causing resistance to PI3K-targeted therapy. Both Ptpn22 and Mll3 inactivation resulted in disruption of mammary gland differentiation and an increase in stem cell activity. Mechanistically, Mll3 deletion enhanced stem cell activity through activation of the HIF pathway. Thus, our study has established a robust in vivo platform for functional cancer genomics and has discovered functional breast cancer mutations. PMID- 27653683 TI - Parent-of-Origin DNA Methylation Dynamics during Mouse Development. AB - Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults. To test this hypothesis, we targeted a reporter for genomic methylation to the imprinted Dlk1-Dio3 intergenic DMR (IG-DMR) to assess the methylation of both parental alleles at single-cell resolution. Biallelic gain or loss of IG-DMR methylation occurred in a small fraction of mouse embryonic stem cells, significantly affecting developmental potency. Mice carrying the reporter in either parental allele showed striking parent-specific changes in IG-DMR methylation, causing substantial and consistent tissue- and cell-type-dependent signatures in embryos and postnatal animals. Furthermore, dynamics in DNA methylation persisted during adult neurogenesis, resulting in inter-individual diversity. This substantial cell-cell DNA methylation heterogeneity implies that dynamic DNA methylation variations in the adult may be of functional importance. PMID- 27653686 TI - Quantitative Lipid Droplet Proteome Analysis Identifies Annexin A3 as a Cofactor for HCV Particle Production. AB - Lipid droplets are vital to hepatitis C virus (HCV) infection as the putative sites of virion assembly, but morphogenesis and egress of virions remain ill defined. We performed quantitative lipid droplet proteome analysis of HCV infected cells to identify co-factors of that process. Our results demonstrate that HCV disconnects lipid droplets from their metabolic function. Annexin A3 (ANXA3), a protein enriched in lipid droplet fractions, strongly impacted HCV replication and was characterized further: ANXA3 is recruited to lipid-rich fractions in HCV-infected cells by the viral core and NS5A proteins. ANXA3 knockdown does not affect HCV RNA replication but severely impairs virion production with lower specific infectivity and higher density of secreted virions. ANXA3 is essential for the interaction of viral envelope E2 with apolipoprotein E (ApoE) and for trafficking, but not lipidation, of ApoE in HCV infected cells. Thus, we identified ANXA3 as a regulator of HCV maturation and egress. PMID- 27653685 TI - Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase. AB - MORC3 is linked to inflammatory myopathies and cancer; however, the precise role of MORC3 in normal cell physiology and disease remains poorly understood. Here, we present detailed genetic, biochemical, and structural analyses of MORC3. We demonstrate that MORC3 is significantly upregulated in Down syndrome and that genetic abnormalities in MORC3 are associated with cancer. The CW domain of MORC3 binds to the methylated histone H3K4 tail, and this interaction is essential for recruitment of MORC3 to chromatin and accumulation in nuclear bodies. We show that MORC3 possesses intrinsic ATPase activity that requires DNA, but it is negatively regulated by the CW domain, which interacts with the ATPase domain. Natively linked CW impedes binding of the ATPase domain to DNA, resulting in a decrease in the DNA-stimulated enzymatic activity. Collectively, our studies provide a molecular framework detailing MORC3 functions and suggest that its modulation may contribute to human disease. PMID- 27653684 TI - Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. AB - B cell CLL/lymphoma 11A (BCL11A) is a transcription factor and regulator of hemoglobin switching that has emerged as a promising therapeutic target for sickle cell disease and thalassemia. In the hematopoietic system, BCL11A is required for B lymphopoiesis, yet its role in other hematopoietic cells, especially hematopoietic stem cells (HSCs) remains elusive. The extensive expression of BCL11A in hematopoiesis implicates context-dependent roles, highlighting the importance of fully characterizing its function as part of ongoing efforts for stem cell therapy and regenerative medicine. Here, we demonstrate that BCL11A is indispensable for normal HSC function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. We find that downregulation of cyclin-dependent kinase 6 (Cdk6), and the ensuing cell-cycle delay, correlate with HSC dysfunction. Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A. PMID- 27653687 TI - IL-4 Induces Metallothionein 3- and SLC30A4-Dependent Increase in Intracellular Zn(2+) that Promotes Pathogen Persistence in Macrophages. AB - Alternative activation of macrophages promotes wound healing but weakens antimicrobial defenses against intracellular pathogens. The mechanisms that suppress macrophage function to create a favorable environment for pathogen growth remain elusive. We show that interleukin (IL)-4 triggers a metallothionein 3 (MT3)- and Zn exporter SLC30A4-dependent increase in the labile Zn(2+) stores in macrophages and that intracellular pathogens can exploit this increase in Zn to survive. IL-4 regulates this pathway by shuttling extracellular Zn into macrophages and by activating cathepsins that act on MT3 to release bound Zn. We show that IL-4 can modulate Zn homeostasis in both human monocytes and mice. In vivo, MT3 can repress macrophage function in an M2-polarizing environment to promote pathogen persistence. Thus, MT3 and SLC30A4 dictate the size of the labile Zn(2+) pool and promote the survival of a prototypical intracellular pathogen in M2 macrophages. PMID- 27653688 TI - iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation. AB - iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against bacterial infections, including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the specific iNKT cell ligand alpha galactosylceramide or S. pneumoniae infection. In untreated mice, the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either alpha-GalCer or S. pneumoniae induced CD1d dependent rapid recruitment of neutrophils out of the vasculature. The neutrophils guided iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell recruitment by blocking CCL17 increased susceptibility to S. pneumoniae infection, suggesting a critical role for the influx of iNKT cells in host defense. PMID- 27653689 TI - Human iNKT Cells Promote Protective Inflammation by Inducing Oscillating Purinergic Signaling in Monocyte-Derived DCs. AB - Invariant natural killer T (iNKT) cells are innate T lymphocytes that promote host defense against a variety of microbial pathogens. Whether microbial ligands are required for their protective effects remains unclear. Here, we show that iNKT cells stimulate human-monocyte-derived dendritic cells (DCs) to produce inflammatory mediators in a manner that does not require the presence of microbial compounds. Interleukin 2 (IL-2)-exposed iNKT cells selectively induced repeated cytoplasmic Ca(2+) fluxes in DCs that were dependent on signaling by the P2X7 purinergic receptor and mediated by ATP released during iNKT-DC interactions. Exposure to iNKT cells led to DC cyclooxygenase 2 (PTGS2) gene transcription, and release of PGE2 that was associated with vascular permeabilization in vivo. Additionally, soluble factors were released that induced neutrophil recruitment and activation and enhanced control of Candida albicans. These results suggest that sterile interactions between iNKT cells and monocyte-derived DCs lead to the production of non-redundant inflammatory mediators that promote neutrophil responses. PMID- 27653690 TI - Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection. AB - Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection. PMID- 27653692 TI - Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity. AB - How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine tuning of CD8alphabeta co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A) is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. KAT6A-deficient CD8(+) T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding linked to reduced Cd8alpha transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR signaling intensity and accelerated contraction of the effector-like memory compartment, whereas the long-lived memory compartment appeared unaffected, a result phenocopied by the removal of the Cd8 E8I enhancer element. These findings suggest a direct role of CD8alphabeta co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool. PMID- 27653691 TI - Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKClambda/iota. AB - Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5(+) stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here, we show that PKClambda/iota is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKClambda/iota in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKClambda/iota expression in human Paneth cells decreases with progression of Crohn's disease. Kaplan-Meier survival analysis of colorectal cancer (CRC) patients revealed that low PRKCI levels correlated with significantly worse patient survival rates. Therefore, PKClambda/iota is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis. PMID- 27653694 TI - Sterile Inflammation Enhances ECM Degradation in Integrin beta1 KO Embryonic Skin. AB - Epidermal knockout of integrin beta1 results in complete disorganization of the basement membrane (BM), resulting in neonatal lethality. Here, we report that this disorganization is exacerbated by an early embryonic inflammatory response involving the recruitment of tissue-resident and monocyte-derived macrophages to the dermal-epidermal junction, associated with increased matrix metalloproteinase activity. Remarkably, the skin barrier in the integrin beta1 knockout animals is intact, suggesting that this inflammatory response is initiated in a sterile environment. We demonstrate that the molecular mechanism involves de novo expression of integrin alphavbeta6 in the basal epidermal cells, which activates a TGF-beta1 driven inflammatory cascade resulting in upregulation of dermal NF kappaB in a Tenascin C-dependent manner. Importantly, treatment of beta1 KO embryos in utero with small molecule inhibitors of TGF-betaR1 and NF-kappaB results in marked rescue of the BM defects and amelioration of immune response, revealing an unconventional immuno-protective role for integrin beta1 during BM remodeling. PMID- 27653693 TI - Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs. AB - DYT1 dystonia is a neurodevelopmental disease that manifests during a discrete period of childhood. The disease is caused by impaired function of torsinA, a protein linked to nuclear membrane budding. The relationship of NE budding to neural development and CNS function is unclear, however, obscuring its potential role in dystonia pathogenesis. We find NE budding begins and resolves during a discrete neurodevelopmental window in torsinA null neurons in vivo. The developmental resolution of NE budding corresponds to increased torsinB protein, while ablating torsinB from torsinA null neurons prevents budding resolution and causes lethal neural dysfunction. Developmental changes in torsinB also correlate with NE bud formation in differentiating DYT1 embryonic stem cells, and overexpression of torsinA or torsinB rescues NE bud formation in this system. These findings identify a torsinA neurodevelopmental window that is essential for normal CNS function and have important implications for dystonia pathogenesis and therapeutics. PMID- 27653695 TI - The RNA Exosome Channeling and Direct Access Conformations Have Distinct In Vivo Functions. AB - The RNA exosome is a 3'-5' ribonuclease complex that is composed of nine core subunits and an essential catalytic subunit, Rrp44. Two distinct conformations of Rrp44 were revealed in previous structural studies, suggesting that Rrp44 may change its conformation to exert its function. In the channeling conformation, (Rrp44(ch)), RNA accesses the active site after traversing the central channel of the RNA exosome, whereas in the other conformation, (Rrp44(da)), RNA gains direct access to the active site. Here, we show that the Rrp44(da) exosome is important for nuclear function of the RNA exosome. Defects caused by disrupting the direct access conformation are distinct from those caused by channel-occluding mutations, indicating specific functions for each conformation. Our genetic analyses provide in vivo evidence that the RNA exosome employs a direct-access route to recruit specific substrates, indicating that the RNA exosome uses alternative conformations to act on different RNA substrates. PMID- 27653696 TI - APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S Phase Entry. AB - The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems. PMID- 27653697 TI - Molecular and Biological Compatibility with Host Alpha-Synuclein Influences Fibril Pathogenicity. AB - The accumulation and propagation of misfolded alpha-synuclein (alpha-Syn) is a central feature of Parkinson's disease and other synucleinopathies. Molecular compatibility between a fibrillar seed and its native protein state is a major determinant of amyloid self-replication. We show that cross-seeded aggregation of human (Hu) and mouse (Ms) alpha-Syn is bidirectionally restricted. Although fibrils formed by Hu-Ms-alpha-Syn chimeric mutants can overcome this inhibition in cell-free systems, sequence homology poorly predicts their efficiency in inducing alpha-Syn pathology in primary neurons or after intracerebral injection into wild-type mice. Chimeric alpha-Syn fibrils demonstrate enhanced or reduced pathogenicities compared with wild-type Hu- or Ms-alpha-Syn fibrils. Furthermore, alpha-Syn mutants induced to polymerize by fibrillar seeds inherit the functional properties of their template, suggesting that transferable pathogenic and non pathogenic states likely influence the initial engagement between exogenous alpha Syn seeds and endogenous neuronal alpha-Syn. Thus, transmission of synucleinopathies is regulated by biological processes in addition to molecular compatibility. PMID- 27653698 TI - RNF4-Dependent Oncogene Activation by Protein Stabilization. AB - Ubiquitylation regulates signaling pathways critical for cancer development and, in many cases, targets proteins for degradation. Here, we report that ubiquitylation by RNF4 stabilizes otherwise short-lived oncogenic transcription factors, including beta-catenin, Myc, c-Jun, and the Notch intracellular-domain (N-ICD) protein. RNF4 enhances the transcriptional activity of these factors, as well as Wnt- and Notch-dependent gene expression. While RNF4 is a SUMO-targeted ubiquitin ligase, protein stabilization requires the substrate's phosphorylation, rather than SUMOylation, and binding to RNF4's arginine-rich motif domain. Stabilization also involves generation of unusual polyubiquitin chains and docking of RNF4 to chromatin. Biologically, RNF4 enhances the tumor phenotype and is essential for cancer cell survival. High levels of RNF4 mRNA correlate with poor survival of a subgroup of breast cancer patients, and RNF4 protein levels are elevated in 30% of human colon adenocarcinomas. Thus, RNF4-dependent ubiquitylation translates transient phosphorylation signal(s) into long-term protein stabilization, resulting in enhanced oncoprotein activation. PMID- 27653699 TI - Elucidating the Neuronal Architecture of Olfactory Glomeruli in the Drosophila Antennal Lobe. AB - Olfactory glomeruli are morphologically conserved spherical compartments of the olfactory system, distinguishable solely by their chemosensory repertoire, anatomical position, and volume. Little is known, however, about their numerical neuronal composition. We therefore characterized their neuronal architecture and correlated these anatomical features with their functional properties in Drosophila melanogaster. We quantitatively mapped all olfactory sensory neurons (OSNs) innervating each glomerulus, including sexually dimorphic distributions. Our data reveal the impact of OSN number on glomerular dimensions and demonstrate yet unknown sex-specific differences in several glomeruli. Moreover, we quantified uniglomerular projection neurons for each glomerulus, which unraveled a glomerulus-specific numerical innervation. Correlation between morphological features and functional specificity showed that glomeruli innervated by narrowly tuned OSNs seem to possess a larger number of projection neurons and are involved in less lateral processing than glomeruli targeted by broadly tuned OSNs. Our study demonstrates that the neuronal architecture of each glomerulus encoding crucial odors is unique. PMID- 27653700 TI - The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate. PMID- 27653701 TI - The Histone Chaperone FACT Contributes to DNA Replication-Coupled Nucleosome Assembly. PMID- 27653702 TI - DNA Barcoding of Philippine Herbal Medicinal Products. AB - The Philippine government established the Traditional and Alternative Medicine Act in 1997 to promote traditionally used herbal products and to provide an effective yet affordable alternative to conventional medicines. However, government regulation of herbal medicinal products (HMPs) is not stringent, relying only on submitted quality data from the manufacturer. In this study we validated the taxonomic identity of 26 plant samples contained within 22 HMPs, each produced by different local manufacturers, through DNA barcoding of the nuclear internal transcribed spacer-2 (ITS2) region. We recovered 19 ITS2 barcodes from 26 samples. These were compared to sequences in GenBank using MEGABLAST, but ambiguous results (similar max scores for different species) were phylogenetically analyzed. Twelve of the 19 samples matched the indicated species on the product label, three were equivocal in specific identity but were placed in the expected genus, and four other samples from three manufacturers contained contamination and/or substitution. GenBank's reference database was at times problematic because some sequences were lacking or were misidentified, but the database was still useful. Overall, ITS2 barcoding was successful in authenticating the HMPs, and it is recommended during the premarket evaluation process so as to obtain a certificate of registration from the government. The government should also develop a comprehensive database of barcodes for Philippine plants, and should prioritize the development of the traditional pharmacopeia because many locally produced HMPs are not indigenous. PMID- 27653703 TI - Indoor allergen exposure and asthma outcomes. AB - PURPOSE OF REVIEW: The aim of the present review is to discuss updates on research regarding the relationship between indoor allergen exposure and childhood asthma with a focus on clinical effects, locations of exposure, and novel treatments. RECENT FINDINGS: Recent data continue to demonstrate that early life sensitization to indoor allergens is a predictor of asthma development later in life. Furthermore, avoidance of exposure to these allergens continues to be important especially given that the vast majority of children with asthma are sensitized to at least one indoor allergen. New research suggests that mouse allergen, more so than cockroach allergen, may be the most relevant urban allergen. Recent evidence reminds us that children are exposed to clinically important levels of indoor allergens in locations away from their home, such as schools and daycare centers. Exposure to increased levels of indoor mold in childhood has been associated with asthma development and exacerbation of current asthma; however, emerging evidence suggests that early exposure to higher fungal diversity may actually be protective for asthma development. Novel treatments have been developed that target TH2 pathways thus decreasing asthmatic responses to allergens. These therapies show promise for the treatment of severe allergic asthma refractory to avoidance strategies and standard therapies. SUMMARY: Understanding the relationship between indoor allergens and asthma outcomes is a constantly evolving study of timing, location, and amount of exposure. PMID- 27653705 TI - Diradical Character-Based Design for Singlet Fission of Bisanthene Derivatives: Aromatic-Ring Attachment and pi-Plane Twisting. AB - We demonstrate a diradical character-based molecular design for singlet fission using polycyclic aromatic hydrocarbons, bisanthene derivatives. Two types of chemical modifications-aromatic-ring attachment and pi-plane twisting-are examined in order to satisfy the energy level matching condition for singlet fission. Detailed analysis of the electronic structures of the model molecules using nucleus-independent chemical shift, molecular orbitals, and their energies has demonstrated the usefulness of the relationship between the resonance structure and aromaticity and that between nonplanarity of pi-conjugated systems and reduction of orbital overlap for tuning the diradical character. This result provides a novel design guideline for polycyclic aromatic hydrocarbons toward efficient singlet fission. PMID- 27653706 TI - Diagnosis of Latent Tuberculous Infection. PMID- 27653707 TI - Diagnosis of Latent Tuberculous Infection. PMID- 27653708 TI - Diagnosis of Latent Tuberculous Infection. PMID- 27653709 TI - Acupuncture for Menopausal Hot Flashes. PMID- 27653710 TI - Acupuncture for Menopausal Hot Flashes. PMID- 27653711 TI - Acupuncture for Menopausal Hot Flashes. PMID- 27653713 TI - Radiation-Induced Breast Cancer. PMID- 27653712 TI - Acupuncture for Menopausal Hot Flashes. PMID- 27653704 TI - Methylmalonic and propionic acidemias: clinical management update. AB - PURPOSE OF REVIEW: Recent clinical studies and management guidelines for the treatment of the organic acidopathies methylmalonic acidemia (MMA) and propionic acidemia address the scope of interventions to maximize health and quality of life. Unfortunately, these disorders continue to cause significant morbidity and mortality due to acute and chronic systemic and end-organ injury. RECENT FINDINGS: Dietary management with medical foods has been a mainstay of therapy for decades, yet well controlled patients can manifest growth, development, cardiac, ophthalmological, renal, and neurological complications. Patients with organic acidopathies suffer metabolic brain injury that targets specific regions of the basal ganglia in a distinctive pattern, and these injuries may occur even with optimal management during metabolic stress. Liver transplantation has improved quality of life and metabolic stability, yet transplantation in this population does not entirely prevent brain injury or the development of optic neuropathy and cardiac disease. SUMMARY: Management guidelines should identify necessary screening for patients with methylmalonic acidemia and propionic acidemia, and improve anticipatory management of progressive end-organ disease. Liver transplantation improves overall metabolic control, but injury to nonregenerative tissues may not be mitigated. Continued use of medical foods in these patients requires prospective studies to demonstrate evidence of benefit in a controlled manner. PMID- 27653714 TI - Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression. PMID- 27653715 TI - Radiation-Induced Breast Cancer. PMID- 27653716 TI - Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression. PMID- 27653718 TI - Flight: For Sophia. PMID- 27653717 TI - Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression. PMID- 27653719 TI - Web Exclusives. The Consult Guys - Risk With Atrial Fibrillation: A Guy Thing? PMID- 27653720 TI - Annals for Educators - 20 September 2016. PMID- 27653721 TI - Annals for Hospitalists - 20 September 2016. PMID- 27653722 TI - Web Exclusives. Annals for Hospitalists Inpatient Notes - Oral Anticoagulation for the Hospitalist-Expanded Choices Improve Patient-Centered Care. PMID- 27653723 TI - Evidence-Based Guideline: The USPSTF recommends screening for colorectal cancer in adults 50 to 75 years of age. PMID- 27653724 TI - Pooled RCTs: After ischemic stroke or TIA, aspirin for secondary prevention reduced early recurrence and severity. PMID- 27653725 TI - Review: Omega-3 HUFAs added to antidepressant therapy may reduce depression symptoms. PMID- 27653727 TI - Telephone-based CBT reduced insomnia severity more than menopause education in menopausal women. PMID- 27653726 TI - Review: In patients with depressive disorders, EPA-predominant omega-3 HUFAs improve depression symptoms. PMID- 27653728 TI - Review: In severe aortic stenosis, TAVI and conventional surgery do not differ for <= 30-day or <= 1-year mortality. PMID- 27653729 TI - Intensive lowering of systolic BP did not reduce death or disability more than standard lowering in ICH. PMID- 27653730 TI - Intensive glucose-lowering in type 2 diabetes was linked to hypoglycemia in high complexity patients. PMID- 27653731 TI - Long-acting opioids for chronic noncancer pain were linked to mortality. PMID- 27653732 TI - 4 risk assessment models had good calibration but poor discrimination for VTE in hospitalized medical patients. PMID- 27653733 TI - Myoclonic movements of the elbow and wrist as a rare complication of supracondylar humerus fracture in a child. AB - Supracondylar humerus fractures are associated with neurological complications. This report describes a child who suffered from persistent myoclonus-like movements of the elbow and wrist as a consequence of a previous displaced fracture. Symptoms were progressive. Seven years later, sensation was decreased in the ulnar nerve distribution. Palpation of the ulnar nerve exacerbated the myoclonic jerks. As symptoms progressed, electoneuromyography became abnormal. Cubital tunnel release and anterior transposition of the ulnar nerve were required to reach full recovery. Long-term outcome was excellent. In conclusion, myoclonus-like movements are a rare complication of supracondylar humerus fractures, resulting from ulnar nerve injury. PMID- 27653734 TI - Supplemental Feedings for High-Risk Preterm Infants. PMID- 27653736 TI - Complications and Near-Miss Events After Hepatectomy for Living-Related Liver Donation: An Italian Single Center Report of One Hundred Cases. AB - BACKGROUND In healthy individuals, such as liver living donors, potential complications may occur during surgery. Reporting such complications and near miss events is mandatory to improve living donor management and safety. MATERIAL AND METHODS This retrospective study was performed on a prospective database with the aim of providing a brief analysis of the perioperative, medium-term, and long term complications, and the near-miss events in a single center series of 100 consecutive liver resections for adult-to-adult living-donor liver transplantation. RESULTS Only 23.3% of potential living donors underwent surgery. No living donor mortality was reported; 29 patients (29%) experienced at least one complication. Five patients developed mild long-term dysfunction; two aborted hepatectomies, and there were two near-miss events reported. CONCLUSIONS A strategy for an accurate assessment of living donor complications and strict selection criterion cannot be overemphasized, as well as the need to continuously update center patient outcome reports. PMID- 27653735 TI - Effects of Subsidies and Prohibitions on Nutrition in a Food Benefit Program: A Randomized Clinical Trial. AB - Importance: Strategies to improve the nutritional status of those participating in the Supplemental Nutrition Assistance Program (SNAP) are of interest to policymakers. Objective: To evaluate whether the proposed policy of incentivizing the purchase of fruits and vegetables and prohibiting the purchase of less nutritious foods in a food benefit program improves the nutritional quality of participants' diets. Design, Setting, and Participants: Lower income participants (n = 279) not currently enrolled in SNAP were randomized to 1 of 4 experimental financial food benefit conditions: (1) incentive (30% financial incentive for fruits and vegetables purchased using food benefits); (2) restriction (not allowed to buy sugar sweetened beverages, sweet baked goods, or candies with food benefits); (3) incentive plus restriction (30% financial incentive on fruits and vegetables and restriction of purchase of sugar sweetened beverages, sweet baked goods, or candy with food benefits); or (4) control (no incentive or restrictions on foods purchased with food benefits). Participants in all conditions were given a study-specific debit card where funds were added every 4 weeks for a 12-week period. Outcome measures were collected at baseline and in the final 4 weeks of the experimental period. Main Outcomes and Measures: Primary outcomes (from 24 hour dietary recalls) included intake of energy, discretionary calories, and overall diet quality. Results: A number of favorable changes were observed in the incentive plus restriction condition that were significantly different from changes in the control condition. These included (1) reduced intake of energy ( 96 kcal/d, standard error [SE], 59.9); (2) reduced intake of discretionary calories (-64 kcal/d, SE 26.3); (3) reduced intake of sugar sweetened beverages, sweet baked goods, and candies (-0.6 servings/d, SE 0.2); (4) increased intake of solid fruit (0.2 servings/d, SE 0.1); and (5) improved Healthy Eating Index score (4.1 points, SE 1.4). Fewer improvements were observed in the incentive only and restriction only arms. Conclusions and Relevance: A food benefit program that pairs incentives for purchasing more fruits and vegetables with restrictions on the purchase of less nutritious foods may reduce energy intake and improve the nutritional quality of the diet of participants compared with a program that does not include incentives or restrictions. Clinical Trial Registration: clinicaltrials.gov Identifier: NCT02643576. PMID- 27653737 TI - Physical Activity, Air Pollution, and the Risk of Asthma and Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Physical activity enhances uptake of air pollutants in the lung, possibly augmenting their harmful effects on chronic lung disease during exercise. OBJECTIVES: To examine whether benefits of physical activity with respect to the risk of asthma and chronic obstructive pulmonary disease (COPD) are moderated by exposure to high air pollution levels in an urban setting. METHODS: A total of 53,113 subjects (50-65 yr) from the Danish Diet, Cancer, and Health cohort reported physical activity at recruitment (1993-1997) and were followed until 2013 in the National Patient Register for incident hospitalizations for asthma and COPD. Levels of nitrogen dioxide (NO2) were estimated at subject residences at the time of recruitment. We used Cox regression to associate physical activities and NO2 (high/medium/low) with asthma and COPD, and then introduced an interaction term between each physical activity and NO2. MEASUREMENTS AND MAIN RESULTS: A total of 1,151 subjects were hospitalized for asthma and 3,225 for COPD during 16 years. We found inverse associations of participation in sports (hazard ratio [95% confidence interval]: 0.85 [0.75-0.96]) and cycling (0.85 [0.75-0.96]) with incident asthma, and of participation in sports (0.82 [0.77-0.89]), cycling (0.81 [0.76-0.87]), gardening (0.88 [0.81-0.94]), and walking (0.85 [0.75-0.95]) with incident COPD admissions. We found positive associations between NO2 and incident asthma (1.23 [1.04-1.47]) and COPD (1.15 [1.03-1.27]) hospitalizations (comparing >=21.0 MUg/m3 to <14.3 MUg/m3). We found no interaction between associations of any physical activity and NO2 on incident asthma or COPD hospitalizations. CONCLUSIONS: Increased exposure to air pollution during exercise does not outweigh beneficial effects of physical activity on the risk of asthma and COPD. PMID- 27653738 TI - Direct C(sp3)-H Cross Coupling Enabled by Catalytic Generation of Chlorine Radicals. AB - Here we report the development of a C(sp3)-H cross-coupling platform enabled by the catalytic generation of chlorine radicals by nickel and photoredox catalysis. Aryl chlorides serve as both cross-coupling partners and the chlorine radical source for the alpha-oxy C(sp3)-H arylation of cyclic and acyclic ethers. Mechanistic studies suggest that photolysis of a Ni(III) aryl chloride intermediate, generated by photoredox-mediated single-electron oxidation, leads to elimination of a chlorine radical in what amounts to the sequential capture of two photons. Arylations of a benzylic C(sp3)-H bond of toluene and a completely unactivated C(sp3)-H bond of cyclohexane demonstrate the broad implications of this manifold for accomplishing numerous C(sp3)-H bond functionalizations under exceptionally mild conditions. PMID- 27653740 TI - Neurotypical subjective experience is caused by a hippocampal simulation. AB - We propose that the phenomenon known to neurologically intact people as 'Subjective Experience' is best understood as the activation of various sites in both extrinsic and intrinsic networks by a brand new episodic memory engram (i.e., a complex theta wave coding pattern originating from field CA1 of the hippocampus). Like a media news outlet, the hippocampal complex receives reportage from widely distributed structures around the brain and organizes and binds those reports together into a brand new episodic memory (i.e., a virtual reality, movie-like, unified, contextualized, but vastly simplified summation of what just happened). This memory pattern is then 'broadcast' back to structures across the brain (via bidirectional pathways to and from the entorhinal cortex and perirhinal area) for error correction, to expedite predictive processing, and to inform sites in both extrinsic and intrinsic networks of one unified history. It is the cortical activation by the new episodic memory engram that gives rise to the event of experiencing. Because episodic memory is the only unified and contextualized representation of self-in-the-world in the brain, and because it informs most of the major cortices about 'what just happened,' it is subjectively misinterpreted as the actual interaction of the body/mind with its environment. This misinterpretation offers insight into many of the distinct and mysterious features of neurotypical subjective experience and the pathologies of consciousness. WIREs Cogn Sci 2017, 8:e1412. doi: 10.1002/wcs.1412 For further resources related to this article, please visit the WIREs website. PMID- 27653741 TI - A 92,XXXY Miscarriage Consecutive to a Digynic Triploid Pregnancy. AB - The patient was referred for prenatal diagnosis due to the sonographic finding of a polymalformed male fetus, and an amniocentesis was performed before termination of pregnancy. The pathological study of the placenta did not show morphological alterations. In her next pregnancy, sonographic examination disclosed a missed abortion with a visible embryo, and a chorionic villi sample was obtained for cytogenetic analysis before evacuation. Macroscopic examination of the villi sample did not reveal molar vesicular appearance. QF-PCR and cytogenetic analyses were performed on amniotic fluid (first pregnancy) and chorionic villi samples (second pregnancy). A 69,XXY and 92,XXXY karyotype was found, respectively. QF PCR results disclosed 2 maternal and 1 paternal alleles in the first pregnancy (digynic triploidy), and double maternal and double paternal contribution to the tetraploid pregnancy. Among the few reported cases of 92,XXXY tetraploidy, those associated with partial moles show a PPPM genotype (3 paternal and 1 maternal alleles), and the only case with a PPMM genotype was found in a spontaneously aborted fetus similar to our case. We are not aware of other cases with combination of a digynic triploid pregnancy and a tetraploid pregnancy with a PPMM contribution. Our case adds evidence to the influence of the balance between paternal and maternal genomic doses on the phenotype. PMID- 27653742 TI - Investigating the role of dissolved and droplet oil in aquatic toxicity using dispersed and passive dosing systems. AB - Characterization of the aquatic toxicity of oil is needed to support hazard assessment and inform spill response. Natural processes and mitigation strategies involving dispersant use can result in exposures to both dissolved and droplet oil that are not typically differentiated when oil exposures are characterized in toxicity tests. Thus, the impact of droplets on aquatic toxicity is largely uncharacterized. To improve the understanding of the role of droplets, acute toxicity tests with Daphnia magna and Americamysis bahia were performed with Endicott crude oil in low-energy mixing systems with and without Corexit 9500 dispersant. Exposures were also prepared by placing crude oil in silicone tubing and passively dosing test media to provide dissolved oil exposures without droplets. A framework is described for characterizing dissolved phase exposures using both mechanistic modeling and passive sampling measurements. The approach is then illustrated by application to data from the present study. Expression of toxicity in terms of toxic units calculated from modeled dissolved oil concentrations or passive sampling measurements showed similar dose responses between exposure systems and organisms, despite the gradient in droplet oil. These results indicate that droplets do not appreciably contribute to toxicity for the 2 species investigated and further support hazard evaluation of dispersed oil on the basis of dissolved exposure metrics. Environ Toxicol Chem 2017;36:1020 1028. (c) 2016 SETAC. PMID- 27653743 TI - Lichen planus after rabies vaccination: an example of isovaccinetopic response. PMID- 27653744 TI - Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti coagulant the dicumarol. AB - Chemotherapeutic response is critical for the successful treatment and good prognosis in cancer patients. In this study, we analysed the gene expression profiles of preoperative samples from oestrogen receptor (ER)-negative breast cancer patients with different responses to taxane-anthracycline-based (TA-based) chemotherapy, and identified a group of genes that was predictive. Pregnancy specific beta-1-glycoprotein 1 (PSG1) played a central role within signalling pathways of these genes. Inhibiting PSG1 can effectively reduce chemoresistance via a transforming growth factor-beta (TGF-beta)-related pathway in ER-negative breast cancer cells. Drug screening then identified dicumarol (DCM) to target the PSG1 and inhibit chemoresistance to TA-based chemotherapy in vitro, in vivo, and in clinical samples. Taken together, this study highlights PSG1 as an important mediator of chemoresistance, whose effect could be diminished by DCM. PMID- 27653745 TI - Reversible Electrocatalytic Activity of Carbon-Supported Ptx Ni1-x in Hydrogen Reactions. AB - Hydrogen oxidation and evolution reactions (HOR and HER) are studied on Ptx Ni1-x /C materials synthesized by the bromide anion exchange method. Physicochemical characterization shows that this surfactant-free method enables the preparation of well-dispersed and effective catalysts for the processes involved in the anode of H2 /O2 fuel cells (HOR) and the cathode of water electrolyzers (HER). The Pt based materials are modified with different Ni contents to decrease the amount of costly precious metal in the electrode materials. These modified Pt-based materials are found to be electroactive for both reactions without additional overpotential. Kinetic parameters such as the Tafel slope, exchange (j0 ) and kinetic current densities, and the rate-determining steps of the reaction mechanisms are determined for each Pt-Ni catalyst and compared to those obtained at the Pt/C surface in alkaline medium. The high j0 values that are obtained indicate a probable contribution of the surface structure of the catalysts due to their roughness and the presence of oxygenated Ni species even at low potentials. PMID- 27653746 TI - A model for perception-based identification of sensitive skin. AB - BACKGROUND: With high prevalence of sensitive skin (SS), lack of strong evidence on pathomechanisms, consensus on associated symptoms, proof of existence of 'general' SS and tools to recruit subjects, this topic attracts increasing attention of research. OBJECTIVE: To create a model for selecting subjects in studies on SS by identifying a complete set of self-reported SS characteristics and factors discriminatively describing it. METHODS: A survey (n = 3058) was conducted, comprising questions regarding socio-demographics, atopy, skin characteristics, personal care, degree of self-assessed SS and subjective and objective reactions to endogenous and exogenous factors. Exploratory factor analysis on 481 questionnaires was performed to identify underlying dimensions and multivariate logistic regression to find contributing variables to the likelihood of reporting SS. RESULTS: The prevalence of SS was found to be 41%, and 56% of SS subjects reports a concomitant atopic condition. The most discriminative were the eliciting factors toiletries and emotions, and not specific skin symptoms in general. CONCLUSION: Triggers of different origins seem to elicit SS, it is not defined by concomitant skin diseases only, suggesting existence of 'general' SS. A multifactorial questionnaire could be a better diagnostic than a one-dimensional provocative test. PMID- 27653747 TI - Coughing a fragment without stent failure: a rare presentation of airway stent damage. PMID- 27653748 TI - Genetic Testing in Dermatology: A Survey Analyzing Obstacles to Appropriate Care. AB - BACKGROUND/OBJECTIVES: The past several decades have witnessed unprecedented advances in genomic technology, bringing genetic testing to the forefront of medical practice and moving us towards the practice of personalized medicine. Genetic testing has become an important aspect in preempting and successfully treating diseases in dermatology, yet difficulty remains in regards to obtaining genetic testing for patients. We conducted a survey for pediatric dermatologists in order to try to gauge and understand where difficulties lie in obtaining genetic testing and to analyze how best these issues can be resolved. METHODS: An 18-question survey was emailed to 480 dermatologists who have attended at least one of the last three annual Society for Pediatric Dermatology (SPD) meetings. RESULTS: Virtually all providers encountered at least one situation in which they required genetic testing for a patient (97.3% [n = 108]) and 37.4% indicated needing genetic testing more than six times per year. Of the respondents who had attempted to obtain genetic testing, half were unsuccessful in obtaining coverage more than 75% of the time (45% [n = 32]) and only 7.0% (n = 5) achieved success 75% to 100% of the time. The most common reasons for obtaining genetic testing included the need to provide an accurate diagnosis, followed by the need to provide prognostic information and appropriate medical management. CONCLUSION: The role of genetic testing in the practice of dermatology is expanding, yet obtaining coverage for genetic testing remains a challenge. We propose several solutions as to how this can be remedied. PMID- 27653749 TI - Treatment delay and facility case volume are associated with survival in early stage glottic cancer. AB - OBJECTIVE: To identify and compare treatment and system factors associated with survival in early-stage glottic cancer. STUDY DESIGN: Retrospective study of cases in the Commission on Cancer National Cancer Database. METHODS: Adult patients with early glottic cancer (stage I or II) diagnosed between January 1, 2004, and December 31, 2012, were included. Demographic, tumor, and survival variables were included in the analyses. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. RESULTS: In total, 5,627 patients were included in the study. Treatment factors associated with improved survival included larynx-preserving surgery alone (hazard ratio [HR] 0.740; P = 0.001) and larynx-preserving surgery with radiation (HR 0.837; P = 0.010) when compared to radiotherapy alone. System factors associated with worse survival included intermediate- (HR 1.123; P = 0.047) or low- (HR 1.458; P = 0.017) volume centers; Medicaid (HR 1.882; P < 0.001), Medicare (HR 1.532; P < 0.001), or other government insurance (HR 2.041; P < 0.001); and delay between diagnosis and treatment greater than 100 days (HR 1.605; P = 0.006). CONCLUSION: A number of treatment and system factors were found to be significantly associated with survival when controlling for patient and tumor factors. These may present targets for the improvement of outcomes in early-stage glottic cancers. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:616-622, 2017. PMID- 27653750 TI - Catalytic Asymmetric Synthesis of N-Chiral Amine Oxides. AB - Direct asymmetric synthesis of N-chiral amine oxides was accomplished (up to 91:9 e.r.) by means of a bimetallic titanium catalyst. A hydroxy group situated at the gamma-position of the N stereocenter enables the desired N-oxidation through dynamic kinetic resolution of the trivalent amine substrates. The method was further extended to the kinetic resolution of racemic gamma-amino alcohols with a preexisting stereocenter, giving an important class of enantioenriched (up to 99.9:0.1 e.r.) building blocks that are otherwise difficult to synthesize. PMID- 27653752 TI - The mediating effect of emotional intelligence between emotional labour, job stress, burnout and nurses' turnover intention. AB - This study was designed to construct and test the structural equation modelling on nurses' turnover intention including emotional labour, job stress, emotional intelligence and burnout in order to identify the mediating effect of emotional intelligence between those variables. Emotional labour, job stress and burnout increase turnover intention of nurses. However, emotional intelligence is negatively correlated with emotional labour and reduces job stress, burnout and turnover intention. Structural equation modelling was used to analyse the goodness of fit of the hypothetical model of nurses' turnover intention. Research data were collected via questionnaires from 4 to 22 August 2014 and analysed using SPSS version 18.0 and AMOS version 20.0. The model fit indices for the hypothetical model were suitable for recommended. Emotional intelligence has decreasing effect on turnover intention through burnout, although its direct effect on turnover intention is not significant. Emotional intelligence has mediation effect between emotional labour and burnout. This study's results suggest that increasing emotional intelligence might critically decrease nurses' turnover intention by reducing the effect of emotional labour on burnout. PMID- 27653751 TI - The usefulness of cone-beam computed tomography during chemoembolization of hepatocellular carcinomas fed exclusively by the cystic artery. AB - PURPOSE: To evaluate the usefulness of cone-beam computed tomography (CBCT) for monitoring the transcatheter arterial chemoembolization (TACE) of hepatocellular carcinomas supplied by the cystic artery. MATERIALS AND METHODS: In seven tumors (mean diameter: 19 mm), the iodized oil distributions in the tumor and gallbladder wall were evaluated by CBCT after injecting iodized oil emulsion (LipCBCT) through the cystic artery. Gelatin sponge particles were injected to completely obstruct the tumor-feeding vessel when iodized oil deposition was seen in less than one third of the wall circumference. The following parameters were retrospectively investigated: (1) the iodized oil distribution during LipCBCT and on CT scans 1 week after TACE; (2) local tumor control; and (3) complications. RESULTS: LipCBCT showed iodized oil accumulation throughout the entire tumor in all cases, and iodized oil deposition in the gallbladder wall in three cases (43 %) (less than one third of the circumference). Therefore, gelatin sponge particles were used in all cases. CT 1 week after TACE showed an almost identical iodized oil distribution to intraoperative LipCBCT. None of the tumors recurred during follow-up, and no complications occurred. CONCLUSION: CBCT is useful for evaluating the distribution of iodized oil in TACE via the cystic artery. PMID- 27653753 TI - A randomized controlled trial of a home-based training programme to decrease depression in family caregivers of persons with dementia. AB - AIMS: The aim of this study was to explore distinct trajectories of caregivers' depressive symptoms and the effects of a training programme on these trajectories over 18 months after the programme. BACKGROUND: Overall effects of caregiver training programmes on family caregivers' depressive symptoms have been reported, but few studies explored distinct courses of changes in caregivers' depressive symptoms and followed up intervention effects on these distinct courses. DESIGN: Randomized clinical trial. METHODS: Family caregivers (n = 116) were randomly assigned into experimental (n = 57) and control (n = 59) groups. The experimental group received the training programme with telephone consultation and the control group received written educational materials and social telephone follow-ups. Caregivers' depressive symptoms were assessed from June 2009 - March 2012 by self completed questionnaires before, at 2 weeks and 3, 6, 12 and 18 months after the intervention. Groups of individual trajectories were distinguished using group based trajectory modelling. RESULTS: Caregivers' depressive symptoms fell into three stable trajectories: non-depressed, mildly blue and depressed. After controlling for covariates, caregivers who received the caregiver-training programme were less likely than those who did not experience persistent depressive symptoms (b = -1.92, odds ratio = 0.15, P < 0.05). CONCLUSION: Depressive symptoms of family caregivers of persons with dementia were relatively stable and followed three distinct courses: non-depressed, mildly blue and depressed. Therefore, caregivers' depressive symptoms should be assessed as early as possible. Caregivers in the experimental group had a lower probability of persistent depressive symptoms than caregivers in the control group. Therefore, this training programme can be used by healthcare providers for persons with dementia and their caregivers. TRIAL REGISTRATION NUMBER: NCT02667951. PMID- 27653754 TI - Nonlinear Flow Rate Response to Pumping Frequency and Reduced Hemolysis in the Drastically Under-Occluded Pulsatile Roller Pump. AB - Roller pumps are widely used in many medical procedures including cardiopulmonary bypass, left/right ventricular assist, and hemodialysis. However, to date, the problem of the roller pumping mechanism causing significant hemolysis remains unresolved. It has been shown that with under-occlusion of the roller pump, hemolysis can be reduced, but significant reduction of the mean flow rate also takes place due to backflow through the under-occlusion. We performed an investigation of the flow dynamics of an under-occluded roller pump which featured significantly higher amount of under-occlusion than previously investigated. Our results showed that the mean flow rate produced by the pump has a strong, nonlinear dependence on pumping frequency. Mean flow rate generally increases with the pumping frequency and the degree of maximum occlusion except at certain frequencies where sharp reductions were observed. These frequencies coincide with the fundamental frequency of the system and its harmonics, bearing resemblance to the impedance pump, suggesting that the drastically under-occluded roller pump is a unique device that employs the pumping mechanisms of both roller pumping and impedance pumping. At the appropriate frequencies, this under occluded roller pump could sustain sufficiently high flow rates for clinical uses. Blood damage potential of the under-occluded roller pump was compared to a fully occluded roller pump via the assay of free-plasma hemoglobin, and it was found that the under-occlusion reduced hemolysis by about half for any given flow rate. The drastically under-occluded roller pumping reported in this study, therefore, has the potential of being translated into an improved clinical blood pump. PMID- 27653755 TI - Progress of Chiral Schiff Bases with C1 Symmetry in Metal-Catalyzed Asymmetric Reactions. AB - In this Personal Account, various chiral Schiff base-metal-catalyzed enantioselective organic reactions are reported; the Schiff bases used were O,N,O as well as N,N,P-tridentate ligands and N,N-bidentate ligands having C1 symmetry. In particular, the enantioselective addition of trimethylsilyl cyanide, dialkylzinc, and organozinc halides to aldehydes, enantioselective 1,4-addition of dialkylzinc to cyclic and acyclic enones, and asymmetric allylic oxidation are reported. Typically, ketimine-type Schiff base-metal complexes exhibited higher reactivity and enantioselectivity compared with the corresponding aldimine-type Schiff base-metal complexes. Notably, remarkable ligand acceleration was observed for all reactions. The obtained products can be used as key intermediates for optically active natural products and pharmaceuticals. PMID- 27653756 TI - Informal caregivers of people with an intellectual disability in England: health, quality of life and impact of caring. AB - There is wide variation in reported impact of caring on caregiver well-being, and often a negative appraisal of caregiving. Researchers are beginning to question the robustness of the evidence base on which negative appraisals are based. The present study aimed to draw on data from a population-representative sample to describe the health, quality of life and impact of caring of informal caregivers of people with an intellectual disability. Informal carers of people with intellectual disability (N = 260) were identified among 2199 carers in the English Survey of Carers in Households 2009/10. Generalised estimating equations explored the association between socio-demographic and caring profile with quality of life, physical health status, and impact on psychological health and personal life. Compared to other caregivers, providing care to a person with intellectual disability was not associated with reduced quality of life. There was an 82% increased risk of reporting poorer health status, even though poorer health was not likely to be attributed to care-giving. A higher risk of negative impact on personal life was seen in comparison with the wider group of caregivers, but not in comparison with more similar-sized caregiver groups (mental health or dementia). Carers of people with intellectual disability were more likely to be struggling financially and have a high caring load. These factors were systematically related to lower well-being. A uniformly negative appraisal of caring for people with intellectual disability was not supported by these English population-representative data. Poverty and long care-giving hours may make caregivers more susceptible to negative well-being. Support for caregivers of people with intellectual disability should focus on alleviating those two factors. PMID- 27653759 TI - Solid-State Spectroscopic Investigation of Molecular Interactions between Clofazimine and Hypromellose Phthalate in Amorphous Solid Dispersions. AB - It has been technically challenging to specify the detailed molecular interactions and binding motif between drugs and polymeric inhibitors in the solid state. To further investigate drug-polymer interactions from a molecular perspective, a solid dispersion of clofazimine (CLF) and hypromellose phthalate (HPMCP), with reported superior amorphous drug loading capacity and physical stability, was selected as a model system. The CLF-HPMCP interactions in solid dispersions were investigated by various solid state spectroscopic methods including ultraviolet-visible (UV-vis), infrared (IR), and solid-state NMR (ssNMR) spectroscopy. Significant spectral changes suggest that protonated CLF is ionically bonded to the carboxylate from the phthalyl substituents of HPMCP. In addition, multivariate analysis of spectra was applied to optimize the concentration of polymeric inhibitor used to formulate the amorphous solid dispersions. Most interestingly, proton transfer between CLF and carboxylic acid was experimentally investigated from 2D 1H-1H homonuclear double quantum NMR spectra by utilizing the ultrafast magic-angle spinning (MAS) technique. The molecular interaction pattern and the critical bonding structure in CLF-HPMCP dispersions were further delineated by successfully correlating ssNMR findings with quantum chemistry calculations. These high-resolution investigations provide critical structural information on active pharmaceutical ingredient-polymer interaction, which can be useful for rational selection of appropriate polymeric carriers, which are effective crystallization inhibitors for amorphous drugs. PMID- 27653758 TI - Apixaban: A Review in Venous Thromboembolism. AB - Apixaban (Eliquis(r)) is an oral, direct factor Xa inhibitor that is available for use in the treatment and secondary prevention of venous thromboembolism (VTE). Like other direct oral anticoagulants (DOACs), apixaban has generally predictable pharmacological properties and does not require routine anticoagulation monitoring. In large phase III trials, oral apixaban was noninferior to subcutaneous enoxaparin sodium overlapped with and followed by oral warfarin (enoxaparin/warfarin) in the treatment of adults with acute VTE over 6 months with regard to the incidence of recurrent VTE or VTE-related death (AMPLIFY), and was significantly more effective than placebo in the prevention of recurrent VTE or all-cause mortality over 12 months in patients who had completed 6-12 months' anticoagulation treatment for VTE (AMPLIFY-EXT). Apixaban was generally well tolerated in these trials; the risks of major bleeding and the composite endpoint of major or clinically relevant nonmajor (CRNM) bleeding with apixaban were significantly lower than enoxaparin/warfarin in AMPLIFY and not significantly different from that of placebo in AMPLIFY-EXT. Similarly, in Japanese adults with acute VTE (AMPLIFY-J), apixaban was associated with a significantly lower risk of major or CRNM bleeding than unfractionated heparin plus warfarin, and no cases of recurrent VTE or VTE-related death over 24 weeks. Thus, apixaban is useful therapeutic alternative for the management of adults with VTE. PMID- 27653760 TI - Measuring gait with an accelerometer-based wearable: influence of device location, testing protocol and age. AB - Wearables such as accelerometers are emerging as powerful tools for quantifying gait in various environments. Flexibility in wearable location may improve ease of use and data acquisition during instrumented testing. However, change of location may impact algorithm functionality when evaluating associated gait characteristics. Furthermore, this may be exacerbated by testing protocol (different walking speed) and age. Therefore, the aim of this study was to examine the effect of an accelerometer-based wearable(s) (accW) location, walking speed, age and algorithms on gait characteristics. Forty younger (YA) and 40 older adults (OA) were recruited. Participants wore accW positioned at the chest, waist and lower back (L5, gold standard) and were asked to walk continuously for 2 min at preferred and fast speeds. Two algorithms, previously validated for accW located on L5, were used to quantify step time and step length. Mean, variability and asymmetry gait characteristics were estimated for each location with reference to L5. To examine impact of locations and speed on algorithm-dependant characteristic evaluation, adjustments were made to the temporal algorithm. Absolute, relative agreement and difference between measurements at different locations and L5 were assessed. Mean step time and length evaluated from the chest showed excellent agreement compared to L5 for both age groups and speeds. Agreement between waist and L5 was excellent for mean step time for both speeds and age groups, good for mean step length at both speeds for YA and at preferred speed for OA. Step time and length asymmetry evaluated from the chest showed moderate agreement for YA only. Lastly, results showed that algorithm adjustment did not influence agreement between results obtained at different locations. Mean spatiotemporal characteristics can be robustly quantified from accW at the locations used in this study irrespective of speed and age; this is not true when estimating variability and asymmetry characteristics. PMID- 27653757 TI - Predictors of Response to Multiple Sclerosis Therapeutics in Individual Patients. AB - Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Several disease-modifying therapies have been shown to ameliorate the disease course; however, the individual treatment response and the occurrence of adverse events remain highly unpredictable. In the last 2 decades, a multitude of studies have aimed to identify biomarkers that enable treatment allocation in the individual patient or subgroup of patients with regard to treatment efficacy and safety profile. Following a PubMed database search, we provide an overview on what is presently known about body fluid markers for the prediction of response to the currently approved MS therapeutics. We also discuss the potential use of biomarkers with regard to drug-induced adverse events. To date, only a few molecules have been introduced in clinical routine: anti-drug antibodies against interferon (IFN)-beta and natalizumab that are associated with abolished drug levels and treatment failure; anti-JC virus (JCV) antibody index that allows risk stratification for the development of progressive multifocal leukoencephalopathy (PML), a rare but severe adverse event during natalizumab treatment; and serostatus of varicella zoster virus as screening examination prior to fingolimod therapy to prevent the infection. A few candidate biomarkers still need closer examination, such as type I IFN signature and T-helper cell (Th)-17 reactivity for prediction of IFN-beta treatment response, L-selectin expression for prediction of natalizumab-associated PML, interleukin (IL)-21 levels for prediction of secondary autoimmunity after exposure to alemtuzumab, lymphocyte count with regard to PML risk while receiving dimethyl fumarate or N-terminal-pro B-type natriuretic peptide (NT-proBNP) for monitoring of cardiac side effects during mitoxantrone therapy. PMID- 27653762 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27653761 TI - Bioactive new metabolites from the green alga Udotea orientalis growing on the Gorgonian coral Pseudopterogorgia rigida. AB - As part of our continued search for bioactive secondary metabolites from marine sources using a bioassay-guided fractionation technique (Cytotoxic and anti trypanosome activities), we have examined the organic extract of Papua New Guinean collection of the green alga Udotea orientalis growing on the Gorgonian coral Pseudopterogorgia rigida. Successive HPLC investigations resulted in isolation of three new compounds, (+) curcuepoxide A, (+) curcuepoxide B and (+) 10alpha-hydroxycurcudiol. Analysis of different spectroscopic data e.g. UV, IR, LRMS, HRMS, 1D NMR and 2D NMR on the isolated compounds allowed for construction of the planar structures. Stereochemistry assignment at C-7 and C-10 in the new compounds was discussed. Isolated compounds were found to be active in an in vitro assay of antitrypanosome activity. The isolated compounds were found to have variable cytotoxic activity in human lung cancer cell lines. PMID- 27653764 TI - Alcohol-related injuries. AB - Alcohol is a common presenting factor among patients at EDs and alcohol consumption is especially widespread in people with injuries. PMID- 27653765 TI - Cognitive impairment. AB - The rise in incidence and prevalence of dementia will have a large impact on healthcare systems. Canadian researchers report on a scoping and integrative review of research on cognitive impairment in adults aged 65 and above who visited emergency departments (EDs) between 1990 and 2008, to determine the effectiveness of interventions for this population. PMID- 27653763 TI - Diary. AB - Our roundup of what's on. PMID- 27653766 TI - Septic shock in children. AB - Delayed recognition and inadequate fluid resuscitation in children with septic shock results in suboptimal care. PMID- 27653767 TI - Clinical approach to the diagnosis and treatment of cystic fibrosis and CFTR related disorders. AB - INTRODUCTION: Cystic fibrosis (CF) is the most frequent life-shortening autosomal recessive disorder in Caucasians. Defects or absence of the CF-transmembrane conductance regulator impair ion transport in apical membranes of exocrine glands. Leading symptoms of typical CF are exocrine pancreatic insufficiency and progressive pulmonary destruction, causing premature death. Additionally, patients can suffer from chronic rhinosinusitis, hepatic and intestinal involvement, diabetes and predominantly male infertility. Areas covered: CFTR related disorders affect only one or several different organ systems, often to a milder degree. The definition and usage of the term has seen some variations in the last years, aiming to improve differentiation of the broad clinical spectrum associated with CFTR defects. In this review we present disease characteristics, diagnostic criteria, and treatment options of CFTR-related disorders for a multidisciplinary readership. Expert commentary: CFTR-related disorders are often diagnosed late, leading to lack of specialized attendance and adequate therapy. In clinical care, monitoring of the nutritional status, lung function, airway pathogen colonization and laboratory parameters is necessary to optimize therapy and the course of the disease. PMID- 27653768 TI - Target organ damage in primary hypertensive patients: role of the morning heart rate surge. AB - BACKGROUND: The morning heart rate surge (MHRS) and morning blood pressure surge (MBPS) may be responsible for the high prevalence of cardiovascular events during the morning period. The clinical significance of the MBPS has been well established, but that of the MHRS remains unclear. Thus, we evaluated the association between the MHRS and target organ damage (TOD). METHODS: A cross sectional study of 580 hypertensive patients was performed. MHRS and heart rate variability (HRV) were analyzed by 24 h electrocardiogram. TOD was assessed by estimated glomerular filtration rate, carotid intima-media thickness (IMT), and left ventricular mass index. RESULTS: The prevalence of TOD tended to decrease with sleep-trough MHRS (first to fourth quartiles: 71%, 70.3%, 58.6%, and 52.7%, respectively) or prewaking MHRS quartiles (first to fourth quartiles: 65.3%, 73.6%, 61.4%, and 54.2%, respectively), whereas the opposite trend was observed for standard deviation of all normal NN intervals (SDNN). Moreover, sleep-trough MHRS, prewaking MHRS, SDNN, and SDNN index were significantly lower in patients with TOD than in those without TOD. According to four logistic regression models, the associations of prewaking MHRS, SDNN, and SDNN index with TOD were lost after adjustment for age and BP. Patients in the first (<=11.125 bpm) and second sleep trough MHRS quartiles (11.125-15.75 bpm) had a 1.95-2.06-fold increased risk of TOD compared with those in the fourth quartile (p < 0.05). CONCLUSION: A blunted sleep-trough MHRS, which may serve as a surrogate marker for autonomic imbalance, was independently associated with TOD in primary hypertensive patients. PMID- 27653769 TI - Nonmelanoma Skin Cancer in Nonwhite Organ Transplant Recipients. AB - Importance: Organ transplant recipients have a higher incidence of skin cancer. This risk is magnified over time and with continued exposure to immunosuppression. Skin cancer in nonwhite patients is associated with greater morbidity and mortality owing to diagnosis at a more advanced stage, which suggests that nonwhite organ transplant recipients are at even higher risk. Objective: To describe demographic and clinical factors and the incidence of skin cancer in nonwhite organ transplant recipients. Design, Setting, and Participants: We performed a retrospective medical record review of patients who were organ transplant recipients (154 were white and 259 nonwhite [black, Asian, Hispanic, Pacific Islander]) seen from November 1, 2011, to April 18, 2016 at an academic referral center. Main Outcomes and Measures: Variables were analyzed and compared between racial groups, including sex, age, race/ethnicity, Fitzpatrick type, type and location of skin cancer, type of organ transplanted, time to diagnosis of skin cancer after transplantation, and history of condyloma acuminata and/or verruca vulgaris. Results: Most of the 413 patients (62.7%) evaluated were nonwhite organ transplant recipients; 264 were men, and 149 were women. Their mean (SD) age was 60.09 (13.59) years. Nineteen skin cancers were identified in 15 patients (5.8%) representing 3 racial/ethnic groups: black (6 patients), Asian (5), and Hispanic (4). All squamous cell carcinomas in blacks were diagnosed in the in situ stage, located on sun-protected sites, and occurred in patients whose lesions tested positive for human papilloma virus (HPV) and/or who endorsed a history of condyloma acuminata or verruca vulgaris. Most skin cancers in Asians were located on sun-exposed areas and occurred in individuals who emigrated from equatorial locations. Conclusions and Relevance: Nonwhite organ transplant recipients are at risk for developing skin cancer posttransplantation. Follow-up in a specialized transplant dermatology center and baseline total-body skin examination should be part of posttransplantation care in all organ transplant recipients, including nonwhite patients. A thorough inspection of the groin and genitalia is imperative in black organ transplant recipients. History of HPV infection, particularly in black organ transplant recipients, and sun exposure/emigration history in Asian organ transplant recipients should be documented. Vigilant photoprotection may be of lesser importance in the prevention of skin cancer in black organ transplant recipients. Risk factors for nonwhite organ transplant recipients differ between races/ethnicities and warrant further study in efforts to better counsel and prevent skin cancer in these patients. PMID- 27653770 TI - Dynamics of single photon transport in a one-dimensional waveguide two-point coupled with a Jaynes-Cummings system. AB - We study the dynamics of an ultrafast single photon pulse in a one-dimensional waveguide two-point coupled with a Jaynes-Cummings system. We find that for any single photon input the transmissivity depends periodically on the separation between the two coupling points. For a pulse containing many plane wave components it is almost impossible to suppress transmission, especially when the width of the pulse is less than 20 times the period. In contrast to plane wave input, the waveform of the pulse can be modified by controlling the coupling between the waveguide and Jaynes-Cummings system. Tailoring of the waveform is important for single photon manipulation in quantum informatics. PMID- 27653771 TI - Lasting immune memory against hepatitis B in 12-13-year-old adolescents previously vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. AB - BACKGROUND: Vaccinating infants against hepatitis B virus (HBV) is the most effective way of preventing the disease. However, since HBV exposure can increase during adolescence, it is essential that antibody persistence is maintained. We evaluated the antibody persistence and immune memory against hepatitis B, in 12 13 y olds who had received complete primary + booster vaccination with diphtheria tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b (DTPa-HBV-IPV/Hib) vaccine in infancy. METHODS: Open phase-IV study conducted at 12 centers in Germany [NCT02052661]. Adolescents aged 12-13 y, vaccinated with 4 doses of DTPa-HBV-IPV/Hib (Infanrix hexaTM, GSK Vaccines) in infancy, received a single challenge dose of monovalent pediatric hepatitis B vaccine (EngerixTM-B Kinder; GSK Vaccines). Blood samples were taken before and 1 month post-challenge to measure anti-hepatitis B (anti-HBs) antibodies using a chemiluminescence immunoassay (seroprotection cut-off: >=10 mIU/ml). Post challenge adverse events (AEs) were monitored. RESULTS: 300 subjects were vaccinated; of 293 subjects in the ATP immunogenicity cohort, 60.5% had pre challenge anti-HBs antibodies >=10 mIU/ml, which rose to 97.6% post-challenge (>=100 mIU/ml in 94.1%). An anamnestic response was seen in 96.5% subjects. A 150 fold increase in antibody geometric mean concentrations was observed (22.4 to 3502.6 mIU/ml). Pain (44%) and fatigue (24.3%) were the most frequent solicited local and general AEs, respectively; 14.7% subjects reported unsolicited symptoms during the 31-day post-vaccination period. Two vaccine-unrelated serious AEs occurred. CONCLUSION: Vaccination with DTPa-HBV-IPV/Hib in infancy induces sustained seroprotection and immune memory against HBV, as shown by the strong anamnestic response to the hepatitis B vaccine challenge in 12-13 year-old adolescents. PMID- 27653772 TI - Mouse Specific Cleavage-Resistant RAGE Splice Variant. PMID- 27653773 TI - Third trimester phthalate exposure is associated with DNA methylation of growth related genes in human placenta. AB - Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2 ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth. PMID- 27653774 TI - Improving Initiation and Tracking of Research Projects at an Academic Health Center: A Case Study. AB - Research service cores at academic health centers are important in driving translational advancements. Specifically, biostatistics and research design units provide services and training in data analytics, biostatistics, and study design. However, the increasing demand and complexity of assigning appropriate personnel to time-sensitive projects strains existing resources, potentially decreasing productivity and increasing costs. Improving processes for project initiation, assigning appropriate personnel, and tracking time-sensitive projects can eliminate bottlenecks and utilize resources more efficiently. In this case study, we describe our application of lean six sigma principles to our biostatistics unit to establish a systematic continual process improvement cycle for intake, allocation, and tracking of research design and data analysis projects. The define, measure, analyze, improve, and control methodology was used to guide the process improvement. Our goal was to assess and improve the efficiency and effectiveness of operations by objectively measuring outcomes, automating processes, and reducing bottlenecks. As a result, we developed a web-based dashboard application to capture, track, categorize, streamline, and automate project flow. Our workflow system resulted in improved transparency, efficiency, and workload allocation. Using the dashboard application, we reduced the average study intake time from 18 to 6 days, a 66.7% reduction over 12 months (January to December 2015). PMID- 27653775 TI - Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining. AB - Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug. PMID- 27653777 TI - Teachers' conceptions of learning and teaching in student-centred medical curricula: the impact of context and personal characteristics. AB - BACKGROUND: Gibbs and Coffey (2004) have reported that teaching practices are influenced by teachers' conceptions of learning and teaching. In our previous research we found significant differences between teachers' conceptions in two medical schools with student-centred education. Medical school was the most important predictor, next to discipline, gender and teaching experience. Our research questions for the current study are (1) which specific elements of medical school explain the effect of medical school on teachers' conceptions of learning and teaching? How? and (2) which contextual and personal characteristics are related to conceptions of learning and teaching? How? METHODS: Individual interviews were conducted with 13 teachers of the undergraduate curricula in two medical schools. Previously their conceptions of learning and teaching were assessed with the COLT questionnaire. We investigated the meanings they attached to context and personal characteristics, in relation to their conceptions of learning and teaching. We used a template analysis. RESULTS: Large individual differences existed between teachers. Characteristics mentioned at the medical school and curriculum level were 'curriculum tradition', 'support by educational department' and 'management and finances'. Other contextual characteristics were 'leadership style' at all levels but especially of department chairs, 'affordances and support', 'support and relatedness', and 'students' characteristics'. Personal characteristics were 'agency', 'experience with PBL (as a student or a teacher)','personal development', 'motivation and work engagement'and 'high content expertise'. CONCLUSION: Several context and personal characteristics associated with teachers' conceptions were identified, enabling a broader view on faculty development with attention for these characteristics, next to teaching skills. PMID- 27653778 TI - Plasmodium falciparum proteins involved in cytoadherence of infected erythrocytes to chemokine CX3CL1. AB - Malaria caused by Plasmodium falciparum is associated with cytoadherence of infected red blood cells (iRBC) to endothelial cells. Numerous host molecules have been involved in cytoadherence, including the adhesive chemokine CX3CL1. Most of the identified parasite ligands are from the multigenic and hypervariable Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family which makes them poor targets for the development of a broadly protective vaccine. Using proteomics, we have identified two 25-kDa parasite proteins with adhesive properties for CX3CL1, called CBP for CX3CL1 Binding Proteins. CBPs are coded by single-copy genes with little polymorphic variation and no homology with other P. falciparum gene products. Specific antibodies raised against epitopes from the predicted extracellular domains of each CBP efficiently stain the surface of RBC infected with trophozoites or schizonts, which is a strong indication of CBP expression at the surface of iRBC. These anti-CBP antibodies partially neutralize iRBC adherence to CX3CL1. This adherence is similarly inhibited in the presence of peptides from the CBP extracellular domains, while irrelevant peptides had no such effect. CBP1 and CBP2 are new P. falciparum ligands for the human chemokine CX3CL1. The identification of this non-polymorphic P. falciparum factors provides a new avenue for innovative vaccination approaches. PMID- 27653776 TI - Incidence and Risk Factors for Health-Care Associated Infections after Hip Operation. AB - BACKGROUND: Hip operation reduces pain and improves mobility and quality of life for more than 300,000 people annually, most of whom are more than 65 years old. Substantial increases in surgical volume are projected between 2005 and 2030 in primary total (174%) and revision (137%) procedures. This projection demands that the impact of increasing age on the relative risk of health-care associated infections (HAI) after hip surgical procedures be assessed. Our aim was to examine the incidence and risk factors of HAI among patients who underwent hip operations between 2006 and 2012. PATIENTS AND METHODS: This secondary analysis included data from patients 18 years old or older and having a hip prosthesis procedure in three New York City hospitals between 2006 and 2012. Procedures were categorized as total or partial hip replacements or revision and re-surfacing procedures. Outcomes of interest were blood stream infections (BSI), urinary tract infections (UTI), or surgical site infections (SSI). Patients in whom an infection developed during the hospital visit in which the hip procedure occurred were counted as cases. RESULT: Of 2021 patients, approximately 11% (n = 218) had an HAI. There was no difference in infection rates by admission year despite an increase in surgical volume. SSI was associated with younger age, previous hospitalization, and hip revision surgical procedure whereas UTI and BSI were associated with older age, greater co-morbidity, longer pre-operative length of stay and intensive care unit stay, (p < 0.05). CONCLUSION: HAI after hip operation affected approximately one in 10 patients over a 7-year period in three high-volume hospitals. SSI occurred least frequently, predominantly among patients who underwent revision surgery (without previous SSI), were younger, and had a history of previous hospitalization. Infections such as BSI and UTI, although rare, occurred more frequently and in patients with more co-morbidities, longer pre-operative length of stay, and who required higher level care. Further research to understand these unexpected findings and target interventions is warranted. PMID- 27653779 TI - A covert authentication and security solution for GMOs. AB - BACKGROUND: Proliferation and expansion of security risks necessitates new measures to ensure authenticity and validation of GMOs. Watermarking and other cryptographic methods are available which conceal and recover the original signature, but in the process reveal the authentication information. In many scenarios watermarking and standard cryptographic methods are necessary but not sufficient and new, more advanced, cryptographic protocols are necessary. RESULTS: Herein, we present a new crypto protocol, that is applicable in broader settings, and embeds the authentication string indistinguishably from a random element in the signature space and the string is verified or denied without disclosing the actual signature. Results show that in a nucleotide string of 1000, the algorithm gives a correlation of 0.98 or higher between the distribution of the codon and that of E. coli, making the signature virtually invisible. CONCLUSIONS: This algorithm may be used to securely authenticate and validate GMOs without disclosing the actual signature. While this protocol uses watermarking, its novelty is in use of more complex cryptographic techniques based on zero knowledge proofs to encode information. PMID- 27653780 TI - A novel dendrochronological approach reveals drivers of carbon sequestration in tree species of riparian forests across spatiotemporal scales. AB - Aboveground carbon (C) sequestration in trees is important in global C dynamics, but reliable techniques for its modeling in highly productive and heterogeneous ecosystems are limited. We applied an extended dendrochronological approach to disentangle the functioning of drivers from the atmosphere (temperature, precipitation), the lithosphere (sedimentation rate), the hydrosphere (groundwater table, river water level fluctuation), the biosphere (tree characteristics), and the anthroposphere (dike construction). Carbon sequestration in aboveground biomass of riparian Quercus robur L. and Fraxinus excelsior L. was modeled (1) over time using boosted regression tree analysis (BRT) on cross-datable trees characterized by equal annual growth ring patterns and (2) across space using a subsequent classification and regression tree analysis (CART) on cross-datable and not cross-datable trees. While C sequestration of cross-datable Q. robur responded to precipitation and temperature, cross-datable F. excelsior also responded to a low Danube river water level. However, CART revealed that C sequestration over time is governed by tree height and parameters that vary over space (magnitude of fluctuation in the groundwater table, vertical distance to mean river water level, and longitudinal distance to upstream end of the study area). Thus, a uniform response to climatic drivers of aboveground C sequestration in Q. robur was only detectable in trees of an intermediate height class and in taller trees (>21.8m) on sites where the groundwater table fluctuated little (<=0.9m). The detection of climatic drivers and the river water level in F. excelsior depended on sites at lower altitudes above the mean river water level (<=2.7m) and along a less dynamic downstream section of the study area. Our approach indicates unexploited opportunities of understanding the interplay of different environmental drivers in aboveground C sequestration. Results may support species-specific and locally adapted forest management plans to increase carbon dioxide sequestration from the atmosphere in trees. PMID- 27653781 TI - Psychological and neuropsychological assessment of regular hoasca users. AB - BACKGROUND: Hoasca (also called ayahuasca) is a N,N-dimethyltryptamine (DMT) - containing psychedelic brew originally used for magico-religious purposes by Amerindian populations of the Amazon Basin. Recently, Brazilian syncretic churches have helped spread the ritual use of hoasca to Western societies. The aim of this study was to evaluate substance use, and neuropsychological and psychological functioning of regular hoasca users within a religious setting. METHODS: Assessment of socio-economic status, mood, personality traits, impulsiveness, drug use, quality of life, extrinsic and intrinsic religiosity, and neuropsychological function was performed on 30 volunteers from a U.S. branch of Uniao do Vegetal (UDV), a Brazilian religion which uses hoasca ritually. We also assessed 27 non-hoasca-using control subjects matched by socio-demographic profile and church attendance. Mann-Whitney U, chi-squared and Fisher tests were used to analyze differences between groups. Spearman's association and simple logistic regression tests were used to analyze the impact of frequency of hoasca use on dependent variables. RESULTS: Relative to the control group, the UDV group demonstrated lower scores for depression (p=0.043, r=.27) and confusion (p=0.032, r=.29) as assessed by the Profile of Mood States (POMS); higher scores on the instrument Big Five Inventory (BFI) for the personality traits agreeableness (p=0.028, r=.29) and openness (p=0.037, r=.28); higher scores on the quality life domain role limitations due to physical health as determined by the instrument Medical Outcomes Study Short Form-36 - SF-36 (p=0.035, r=.28); less recent use of alcohol (p<0.001, phic=.57), greater past use of alcohol to intoxication (p=0.007, phic=.36) and past use of cannabis (p=0.001, phic=.45) as measured by the Addiction Severity Index (ASI), 5th edition; better score on a measure of memory vulnerability to proactive interference as measured by the California Verbal Learning Test - CVLT (p=0.040, r=.27). Lifetime use of hoasca was positively correlated with role limitations due to physical health (p=0.032, rs=.39) and negatively associated with lifetime heavy alcohol use (p=0.034, OR=0.979). CONCLUSIONS: The findings indicate that religious use of hoasca does not adversely affect neuropsychological functioning and may have positive effects on substance abuse and mood. PMID- 27653782 TI - The communicative impairment as a core feature of schizophrenia: Frequency of pragmatic deficit, cognitive substrates, and relation with quality of life. AB - BACKGROUND: Impairments in specific aspects of pragmatic competence, supporting the use of language in context, are largely documented in schizophrenia and might represent an indicator of poor outcome. Yet pragmatics is rarely included in clinical settings. This paper aims to promote a clinical consideration of pragmatics as a target of assessment and intervention. We investigated the frequency of the pragmatic deficit, its cognitive substrates, and the relation with quality of life. METHODS: Pragmatic abilities were compared in a sample of patients with schizophrenia and healthy controls based on a comprehensive pragmatic test (APACS). We assessed also for psychopathology, cognition, social cognition, and quality of life. We explored the co-occurrence of deficits in different domains, and we used multiple regressions to investigate the effect of cognition and social cognition on pragmatics, and of pragmatics on quality of life. RESULTS: Pragmatic abilities, especially comprehending discourse and non literal meanings, were compromised in schizophrenia, with 77% of patients falling below cutoff. Pragmatic deficit co-occurred with cognitive or socio-cognitive deficits in approximately 30% of cases. Multiple regression analysis confirmed the interplay of cognition and social cognition in pragmatic behavior. Quality of life was predicted by symptoms and by pragmatic abilities. CONCLUSIONS: The high frequency of impairment suggests that the pragmatic deficit is a core feature of schizophrenia, associated with quality of life. Cognitive and socio-cognitive abilities might represent necessary though not sufficient building blocks for the acquisition of pragmatic abilities throughout development. Therefore, a more precise incorporation of pragmatics in the description of the pathology is of high clinical and translational relevance. PMID- 27653783 TI - Acupuncture for osteoporosis: a systematic review protocol. AB - BACKGROUND: Osteoporosis is a global high prevalence of chronic metabolic disease with serious disability-adjusted life years losing. Acupuncture is used to treat osteoporosis broadly in China and other countries although the evidence on effectiveness cannot give a certain answer. The aim of this systematic review protocol is to appraise the efficacy and safety of acupuncture for osteoporosis. METHODS: A literature search of randomized controlled trials focusing on acupuncture for osteoporosis will be performed in the databases of Medline, Cochrane Library, Web of Science, EBASE, Springer, WHO International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan fang, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP), and other possible resources with a valid search strategy. Outcomes of pain, bone mineral density, fracture, mortality, improvement proportion, biochemical indicators, quality of life, adverse event, and other valid will be extracted and merged for quantitative analysis using Review Manager software (V.5.3.5) or descriptive analysis correspondingly. DISCUSSION: This is the first systematic review to estimate the effect of acupuncture on osteoporosis, and the result may provide evidence to clinical doctor. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037829. PMID- 27653785 TI - Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines. AB - PURPOSE: To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following gamma-ray exposure. MATERIALS AND METHODS: Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells. RESULTS: We report data suggesting that gamma-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy. CONCLUSION: These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals. PMID- 27653784 TI - H2A.Z controls the stability and mobility of nucleosomes to regulate expression of the LH genes. AB - The structure and dynamics of promoter chromatin have a profound effect on the expression levels of genes. Yet, the contribution of DNA sequence, histone post translational modifications, histone variant usage and other factors in shaping the architecture of chromatin, and the mechanisms by which this architecture modulates expression of specific genes are not yet completely understood. Here we use optical tweezers to study the roles that DNA sequence and the histone variant H2A.Z have in shaping the chromatin landscape at the promoters of two model genes, Cga and Lhb. Guided by MNase mapping of the promoters of these genes, we reconstitute nucleosomes that mimic those located near the transcriptional start site and immediately downstream (+1), and measure the forces required to disrupt these nucleosomes, and their mobility along the DNA sequence. Our results indicate that these genes are basally regulated by two distinct strategies, making use of H2A.Z to modulate separate phases of transcription, and highlight how DNA sequence, alternative histone variants and remodelling machinery act synergistically to modulate gene expression. PMID- 27653787 TI - Anatomic and dosimetric changes in patients with head and neck cancer treated with an integrated MRI-tri-60Co teletherapy device. AB - OBJECTIVE: Prior studies have relied on CT to assess alterations in anatomy among patients undergoing radiation for head and neck cancer. We sought to determine the feasibility of using MRI-based image-guided radiotherapy to quantify these changes and to ascertain their potential dosimetric implications. METHODS: 6 patients with head and neck cancer were treated with intensity-modulated radiotherapy (IMRT) on a novel tri-60Co teletherapy system equipped with a 0.35-T MRI (VR, ViewRay Incorporated, Oakwood Village, OH) to 66-70 Gy in 33 fractions (fx). Pre-treatment MRIs on Fx 1, 5, 10, 15, 20, 25, 30 and 33 were imported into a contouring interface, where the primary gross tumour volume (GTV) and parotid glands were delineated. The centre of mass (COM) shifts for these structures were assessed relative to Day 1. Dosimetric data were co-registered with the MRIs, and doses to the GTV and parotid glands were assessed. RESULTS: Primary GTVs decreased significantly over the course of IMRT (median % volume loss, 38.7%; range, 29.5-72.0%; p < 0.05) at a median rate of 1.2%/fx (range, 0.92-2.2%/fx). Both the ipsilateral and contralateral parotid glands experienced significant volume loss (p < 0.05, for all) and shifted medially during IMRT. Weight loss correlated significantly with parotid gland volume loss and medial COM shift (p < 0.05). CONCLUSION: Integrated on-board MRI can be used to accurately contour and analyze primary GTVs and parotid glands over the course of IMRT. COM shifts and significant volume reductions were observed, confirming the results of prior CT based exercises. Advances in knowledge: The superior resolution of on-board MRI may facilitate online adaptive replanning in the future. PMID- 27653786 TI - Dengue Contingency Planning: From Research to Policy and Practice. AB - BACKGROUND: Dengue is an increasingly incident disease across many parts of the world. In response, an evidence-based handbook to translate research into policy and practice was developed. This handbook facilitates contingency planning as well as the development and use of early warning and response systems for dengue fever epidemics, by identifying decision-making processes that contribute to the success or failure of dengue surveillance, as well as triggers that initiate effective responses to incipient outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: Available evidence was evaluated using a step-wise process that included systematic literature reviews, policymaker and stakeholder interviews, a study to assess dengue contingency planning and outbreak management in 10 countries, and a retrospective logistic regression analysis to identify alarm signals for an outbreak warning system using datasets from five dengue endemic countries. Best practices for managing a dengue outbreak are provided for key elements of a dengue contingency plan including timely contingency planning, the importance of a detailed, context-specific dengue contingency plan that clearly distinguishes between routine and outbreak interventions, surveillance systems for outbreak preparedness, outbreak definitions, alert algorithms, managerial capacity, vector control capacity, and clinical management of large caseloads. Additionally, a computer-assisted early warning system, which enables countries to identify and respond to context-specific variables that predict forthcoming dengue outbreaks, has been developed. CONCLUSIONS/SIGNIFICANCE: Most countries do not have comprehensive, detailed contingency plans for dengue outbreaks. Countries tend to rely on intensified vector control as their outbreak response, with minimal focus on integrated management of clinical care, epidemiological, laboratory and vector surveillance, and risk communication. The Technical Handbook for Surveillance, Dengue Outbreak Prediction/ Detection and Outbreak Response seeks to provide countries with evidence-based best practices to justify the declaration of an outbreak and the mobilization of the resources required to implement an effective dengue contingency plan. PMID- 27653789 TI - How Do Adult Survivors of Childhood Sexual Abuse Experience Formally Delivered Talking Therapy? A Systematic Review. AB - This systematic review explored how adult survivors of child sexual abuse experienced nonspecific and trauma-focused talking therapies. Following extensive systematic searches of academic databases, 23 qualitative empirical studies were chosen for review. Using a line-by-line thematic synthesis, four analytical themes developed. These themes were: The Therapeutic Process as a Means for Forming Connections, which discusses therapeutic relationships; Developing a Sense of Self Through the Therapeutic Processes, which identifies stages of developmental recovery; Therapeutic Lights and Black Holes in the Shadows of child sexual abuse, which reflects on how a history of child sexual abuse influenced experiences of therapy; and Healing or Harrowing: Connecting With Others and First-time Experiences, which explores what was helpful, hindering, and new throughout the therapeutic journey. Findings related to participants developing new options for interpersonal relationships through the experience of authentic trust and the experiential learning of control and choice. Recommendations are discussed in relation to developing therapeutic practice and future research. PMID- 27653788 TI - Parasite dynamics in the peripheral blood and the placenta during pregnancy associated malaria infection. AB - BACKGROUND: Malaria infections during pregnancy lead to sequestration of parasite infected red blood cells in the placenta. Placental infection can result in adverse outcomes for mothers and infants. Despite many studies, it remains unclear which peripheral blood infections during pregnancy lead to development of placental malaria. Understanding the timing of peripheral infections that lead to placental malaria and the ability of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP-IPT) and artemisinin-based combination therapy to clear infections will enable the rational design of new interventions to decrease the burden of malaria in pregnancy. METHODS: Microsatellite markers were used to genotype peripheral and placental malaria infections in an observational cohort in Blantyre, Malawi. Genotypes were compared to determine the timing of infections that sequester in the placenta. The effects of SP-IPT and artemether lumefantrine as curative treatment were also evaluated by assessing the occurrence of peripheral infections or matching genotypes between peripheral and placental parasites following treatment. RESULTS: Genotypes from 92 peripheral samples prior to delivery, 26 peripheral samples at delivery, and 29 placental samples were compared. Thirty percent of women with genotyped parasites in their placentas that had peripheral infections detected during pregnancy had matching peripheral-placental genotypes. Matching genotypes were not associated with gestational age and occurred from 13 to 39 weeks. Among women with more than one genotyped peripheral infection during pregnancy, 80 % had persistent infection with the same genotype while the remaining were new infections. Among infections treated with SP or artemether-lumefantrine, 28/84 (33 %) and 9/56 (16 %) had infection detected after treatment, respectively. Recrudescent infections were detected after both treatments and occurred up to 76 days after treatment. Women treated with SP-IPT and artemether-lumefantrine had genotypes matching treated infections detected in the placenta. CONCLUSIONS: Placental malaria can occur at any time during pregnancy. In the context of late enrollment in antenatal care, interventions that protect all women of childbearing age and throughout pregnancy are needed. Currently used medications do not always clear peripheral or placental infections. The ability of anti-malarial drugs to prevent or clear placental infections should be considered in the development of future interventions. PMID- 27653790 TI - Electrochemical Determination of Albendazole at Glassy Carbon Electrode. AB - In this article, the electrochemical behavior on a glassy carbon electrode (GCE) was investigated and the electrochemical parameters of albendazole (ALB) were calculated. ALB effectively accumulated on the GCE surface and caused a pair of redox peaks at around 1.095 V and 1.028 V and an oxidation peak at 0.844 V (versus saturated calomel electrode) in 0.2 M phosphate buffer solution (pH 3.0). Under optimized conditions, the anodic peak current was linear to the ALB concentration the range of 1.5 * 10-7 M to 4.0 * 10-5 M. The regression equation was: Ipa (10-6 A) = 0.79 [ALB] (MUM) + 0.84 (R2 = 0.982). The detection limit 6.08 * 10-8 M was obtained. The proposed method was successfully used to determine ALB content in tablet samples, with satisfactory results. PMID- 27653791 TI - Multistate Mechanism of Lysozyme Denaturation through Synchronous Analysis of Raman Spectra. AB - The denaturation mechanism of hen egg lysozyme is still controversial. In this study, Raman spectroscopy was employed to study the thermal and chemical denaturation mechanisms of lysozyme. All of the Raman bands were synchronously recorded and analyzed during the denaturation process. It was found that the Raman bands of the side groups changed before the bands of skeleton groups. This directly reveals the three-state mechanism of thermal denaturation of lysozyme. The preferential change of the side groups was also observed in the chemical denaturation of lysozyme by guanidine hydrochloride. Moreover, it was found that the Raman bands of the groups on the surface of lysozyme changed before those of the other groups. This indicates that the chemical denaturants interact with the protein surface before the protein core in each step and the chemical denaturation of lysozyme conforms to the multistate and outside-in mechanisms. The synchronous Raman study not only reveals the multistate mechanism of lysozyme denaturation but also demonstrates that this synchronous Raman analysis is a powerful method to study the denaturation mechanisms of other proteins. PMID- 27653792 TI - Aspirin-exacerbated respiratory disease: an update. AB - PURPOSE OF REVIEW: The pathophysiology of aspirin-exacerbated respiratory disease (AERD) is not fully understood and diagnostic methods and so far, treatments for AERD have not been standardized. We summarize recent research into the pathological mechanisms of AERD, diagnostic methods, and treatments for AERD patients. RECENT FINDINGS: In AERD pathophysiology, not only the reduced expression of E prostanoid 2 but also the dysfunction of its pathway could be involved. Moreover, eosinophils of AERD patients could be directly activated by aspirin to produce prostaglandin D2. Platelet activations are well known to be involved in AERD; however, plasma markers do not change during aspirin challenge tests. Additionally, novel genetic polymorphisms, such as P2RY12 and dipeptidyl peptidase 10 gene, and epigenetic predispositions of AERD were found. In AERD diagnosis, bronchial and nasal aspirin challenges have been applied in addition to oral challenge. Serum periostin has been suggested as a potential biomarker for AERD. Apart from standard pharmacological treatment and aspirin desensitization, biologics, including omalizumab and mepolizumab, as well as CRTH2 antagonists have been suggested as promising therapies for AERD treatment. SUMMARY: AERD is usually associated with severe asthma phenotypes. AERD pathophysiology mainly involves the dysregulation of eicosanoid metabolisms, activations of effector cells, which could be influenced by genetic/epigenetic factors. Understanding the pathophysiology of AERD is key to improve the diagnostic methods and proper management of AERD patients. PMID- 27653793 TI - Widefield fluorescence microscopy with sensor-based conjugate adaptive optics using oblique back illumination. AB - We describe a wavefront sensor strategy for the implementation of adaptive optics (AO) in microscope applications involving thick, scattering media. The strategy is based on the exploitation of multiple scattering to provide oblique back illumination of the wavefront-sensor focal plane, enabling a simple and direct measurement of the flux-density tilt angles caused by aberrations at this plane. Advantages of the sensor are that it provides a large measurement field of view (FOV) while requiring no guide star, making it particularly adapted to a type of AO called conjugate AO, which provides a large correction FOV in cases when sample-induced aberrations arise from a single dominant plane (e.g., the sample surface). We apply conjugate AO here to widefield (i.e., nonscanning) fluorescence microscopy for the first time and demonstrate dynamic wavefront correction in a closed-loop implementation. PMID- 27653794 TI - Adaptive optics full-field optical coherence tomography. AB - We describe a simple and compact full-field optical coherence tomography (FFOCT) setup coupled to a transmissive liquid crystal spatial light modulator (LCSLM) to induce or correct aberrations. To reduce the system complexity, strict pupil conjugation was abandoned because low-order aberrations are often dominant. We experimentally confirmed a recent theoretical and experimental demonstration that the image resolution was almost insensitive to aberrations that mostly induce a reduction of the signal level. As a consequence, an image-based algorithm was applied for the optimization process by using the FFOCT image intensity as the metric. Aberration corrections were demonstrated with both an USAF resolution target and biological samples for LCSLM-induced and sample-induced wavefront distortions. PMID- 27653795 TI - Supplemental Feedings for High-Risk Preterm Infants. PMID- 27653796 TI - Estimating National Trends in Inpatient Antibiotic Use Among US Hospitals From 2006 to 2012. AB - Importance: The rising threat of antibiotic resistance and other adverse consequences resulting from the misuse of antibiotics requires a better understanding of antibiotic use in hospitals in the United States. Objective: To use proprietary administrative data to estimate patterns of US inpatient antibiotic use in recent years. Design, Setting, and Participants: For this retrospective analysis, adult and pediatric in-patient antibiotic use data was obtained from the Truven Health MarketScan Hospital Drug Database (HDD) from January 1, 2006, to December 31, 2012. Data from adult and pediatric patients admitted to 1 of approximately 300 participating acute care hospitals provided antibiotic use data for over 34 million discharges representing 166 million patient-days. Main Outcomes and Measures: We retrospectively estimated the days of therapy (DOT) per 1000 patient-days and the proportion of hospital discharges in which a patient received at least 1 dose of an antibiotic during the hospital stay. We calculated measures of antibiotic usage stratified by antibiotic class, year, and other patient and facility characteristics. We used data submitted to the Centers for Medicare and Medicaid Services Healthcare Cost Report Information System to generate estimated weights to apply to the HDD data to create national estimates of antibiotic usage. A multivariate general estimating equation model to account for interhospital covariance was used to assess potential trends in antibiotic DOT over time. Results: During the years 2006 to 2012, 300 to 383 hospitals per year contributed antibiotic data to the HDD. Across all years, 55.1% of patients received at least 1 dose of antibiotics during their hospital visit. The overall national DOT was 755 per 1000 patient-days. Overall antibiotic use did not change significantly over time. The multivariable trend analysis of data from participating hospitals did not show a statistically significant change in overall use (total DOT increase, 5.6; 95% CI, -18.9 to 30.1; P = .65). However, the mean change (95% CI) for the following antibiotic classes increased significantly: third- and fourth-generation cephalosporins, 10.3 (3.1-17.5); macrolides, 4.8 (2.0-7.6); glycopeptides, 22.4 (17.5-27.3); beta-lactam/beta lactamase inhibitor combinations, 18.0 (13.3-22.6); carbapenems, 7.4 (4.6-10.2); and tetracyclines, 3.3 (2.0-4.7). Conclusions and Relevance: Overall DOT of all antibiotics among hospitalized patients in US hospitals has not changed significantly in recent years. Use of some antibiotics, especially broad spectrum agents, however, has increased significantly. This trend is worrisome in light of the rising challenge of antibiotic resistance. Our findings can help inform national efforts to improve antibiotic use by suggesting key targets for improvement interventions. PMID- 27646850 TI - Effect of Fibrin Glue on the Incidence of Surgical Complications After Living Related-Donor Kidney Transplantation: Results of a Randomized Clinical Trial. AB - BACKGROUND The incidence of surgical complications after kidney transplantation ranges from 10-25%. The purpose of this study was to evaluate if the application of fibrin glue as a preventive agent reduces surgical morbidity after a living related-donor kidney transplantation. MATERIAL AND METHODS A controlled clinical trial involving 78 recipients randomly assigned to receive fibrin glue and 79 in the control group without the application of fibrin glue. Patients were followed for six months after surgery. RESULTS The average ages were 24.8+/-9.4 and 27.4+/ 11.3 years in the control and study groups, respectively (p=0.11). Individual morbidities, such as urologic, lymphatic, vascular, and wound complications, were not statistically different between groups; however, the total number of surgical complications observed were in five patients in the study group and 16 patients in the control group. This difference was statistically significant (p<0.01, relative risk 0.44, 95% CI 0.20-0.97). There was no mortality or adverse reaction to fibrin glue. One kidney graft was lost because of uncontrollable bleeding secondary to tearing of the renal capsule. The incidence of early medical complications was similar between groups. CONCLUSIONS Applications of the biological adhesive reduced the incidence of surgical complications. PMID- 27653799 TI - Domino-Like Intercellular Delivery of Undecylenic Acid-Conjugated Porous Silicon Nanoparticles for Deep Tumor Penetration. AB - Improving the intratumoral distribution of anticancer agents remains the critical challenge for developing efficient cancer chemotherapy. Luminescent porous silicon nanoparticles (PSiNPs) have attracted considerable attention in the biomedical field especially in drug delivery. Here, we described the lysosomal exocytosis-mediated domino-like intercellular delivery of undecylenic acid conjugated PSiNPs (UA-PSiNPs) for deep tumor penetration. UA-PSiNPs with significantly improved stability in physiological conditions were internalized into tumor cells by macropinocytosis-, caveolae-, and clathrin-mediated endocytosis and mainly colocalized with Golgi apparatus and lysosomes. Substantial evidence showed that UA-PSiNPs was excreted from cells via lysosomal exocytosis after cellular uptake. The exocytosed UA-PSiNPs induced a domino-like infection of adjacent cancer cells and allowed encapsulated doxorubicin (DOX) to deeply penetrate into both three-dimensional tumor spheroids and in vivo tumors. In addition, DOX-loaded UA-PSiNPs exhibited strong antitumor activity and few side effects in vivo. This study demonstrated that UA-PSiNPs as a drug carrier might be applied for deep tumor penetration, offering a new insight into the design of more efficient delivery systems of anticancer drugs. PMID- 27653798 TI - Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients. AB - RATIONALE: Assessment of fluid responsiveness relies on dynamic echocardiographic parameters that have not yet been compared in large cohorts. OBJECTIVES: To determine the diagnostic accuracy of dynamic parameters used to predict fluid responsiveness in ventilated patients with a circulatory failure of any cause. METHODS: In this multicenter prospective study, respiratory variations of superior vena cava diameter (?SVC) measured using transesophageal echocardiography, of inferior vena cava diameter (?IVC) measured using transthoracic echocardiography, of the maximal Doppler velocity in left ventricular outflow tract (?VmaxAo) measured using either approach, and pulse pressure variations (?PP) were recorded with the patient in the semirecumbent position. In each patient, a passive leg raise was performed and an increase of aortic velocity time integral greater than or equal to 10% defined fluid responsiveness. MEASUREMENTS AND MAIN RESULTS: Among 540 patients (379 men; age, 65 +/- 13 yr; Simplified Acute Physiological Score II, 59 +/- 18; Sequential Organ Failure Assessment, 10 +/- 3), 229 exhibited fluid responsiveness (42%). ?PP, ?VmaxAo, ?SVC, and ?IVC could be measured in 78.5%, 78.0%, 99.6%, and 78.1% of cases, respectively. ?SVC greater than or equal to 21%, ?VmaxAo greater than or equal to 10%, and ?IVC greater than or equal to 8% had a sensitivity of 61% (95% confidence interval, 57-66%), 79% (75-83%), and 55% (50-59%), respectively, and a specificity of 84% (81-87%), 64% (59-69%), and 70% (66-75%), respectively. The area under the receiver operating characteristic curve of ?SVC was significantly greater than that of ?IVC (P = 0.02) and ?PP (P = 0.01). CONCLUSIONS: ?VmaxAo had the best sensitivity and ?SVC the best specificity in predicting fluid responsiveness. ?SVC had a greater diagnostic accuracy than ?IVC and ?PP, but its measurement requires transesophageal echocardiography. PMID- 27653800 TI - One Too Many? Understanding the Influence of Risk Factor Quantity on Perceptions of Risk. AB - Forming a subjective risk judgment in circumstances that feature multiple risk factors is a common, yet complex task. One would expect variations in the number of risk factors in a given situation to have an important influence on risk judgments, yet the exact nature of this influence remains empirically untested. We conducted three studies to address this issue. In Study 1, we found that, when individuals were confronted with a preset number of risk factors (zero, one, two, or three) in the same scenario, their risk judgments were virtually identical for zero, one, and two risk factors, yet markedly higher for three risk factors. By contrast, Study 2 showed that when confronted with variations in the number of risk factors (zero, one, two, and three) for that same scenario, individuals' risk judgments increased/decreased in relatively even increments concurrent with increases/decreases in the number of risk factors. Study 3 identified that pronounced increases in risk judgments, like those observed in Study 1, may occur when the numbers of factors is "high" relative to the potential victim's vulnerability to those factors. Our results show that the number of risk factors in given circumstances can have an important influence on risk judgments and that this influence can differ based on the characteristics of the situation. We discuss how these findings provide a better understanding of subjective risk judgments and highlight the importance of those who seek to communicate risk information being mindful of how data about multiple risk factors could be (mis)interpreted. PMID- 27653801 TI - Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons. AB - Reelin, an extracellular glycoprotein secreted in embryonic and adult brain, participates in neuronal migration and neuronal plasticity. Extensive evidence shows that reelin via activation of the ApoER2 and VLDLR receptors promotes dendrite and spine formation during early development. Further evidence suggests that reelin signaling is needed to maintain a stable architecture in mature neurons, but, direct evidence is lacking. During activity-dependent maturation of the neuronal circuitry, the synaptic protein PSD95 is inserted into the postsynaptic membrane to induce structural refinement and stability of spines and dendrites. Given that ApoER2 interacts with PSD95, we tested if reelin signaling interference in adult neurons reactivates the dendritic architecture. Unlike findings in developing cultures, the presently obtained in vitro and in vivo data show, for the first time, that reelin signaling interference robustly increase dendritogenesis and reduce spine density in mature hippocampal neurons. In particular, the expression of a mutant ApoER2 form (ApoER2-tailless), which is unable to interact with PSD95 and hence cannot transduce reelin signaling, resulted in robust dendritogenesis in mature hippocampal neurons in vitro. These results indicate that reelin/ApoER2/PSD95 signaling is important for neuronal structure maintenance in mature neurons. Mechanistically, obtained immunofluorescent data indicate that reelin signaling impairment reduced synaptic PSD95 levels, consequently leading to synaptic re-insertion of NR2B-NMDARs. Our findings underscore the importance of reelin in maintaining adult network stability and reveal a new mode for reactivating dendritogenesis in neurological disorders where dendritic arbor complexity is limited, such as in depression, Alzheimer's disease, and stroke. J. Cell. Physiol. 232: 1187-1199, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27653803 TI - Evaluation of efficiency and trapping capacity of restricted access media trap columns for the online trapping of small molecules. AB - Restricted access media are generally composed from multi-modal particles that combine a size excluding outer surface and an inner-pore retention mechanism for small molecules. Such materials can be used for either online isolation and pre concentration of target small molecules or removal of small molecule interferences from large macromolecules, such as proteins in complex biological matrices. Thus, they are considered as enhanced online solid-phase extraction materials. We evaluated the efficiency and trapping capacity of different semi permeable surface restricted access media columns (C18 , C8 , and C4 inner pores) for four model small molecule compounds (dopamine hydrochloride, acetaminophen, 4 hydroxybenzoic acid, and diethyl phthalate) having variable physicochemical properties. We further studied the effect of mobile phase flow rate (0.25, 0.5, 1, and 2 mL/min) and pH, using 98:2 0.5% acetic acid in water/ methanol (pH 2.88) and 5 mM ammonium acetate in 98:2 water/methanol (pH 6.61) as mobile phases. Breakthrough curves generated using frontal analysis were analyzed to determine important chromatographic parameters specific for each of the studied compounds. Experimental determination of these parameters allowed selection of the most efficient trap column and the best loading mobile phase conditions for maximal solute enrichment and pre-concentration on restricted access media trap columns. PMID- 27653802 TI - Fiberoptic Contact-Force Sensing Electrophysiological Catheters: How Precise Is the Technology? AB - BACKGROUND: Contact-force (CF) sensing catheters are increasingly used in electrophysiological procedures due to their efficacy and safety profile. As data about the accuracy of fiberoptic CF technology are scarce, we sought to quantify it using in vitro experiments. METHODS AND RESULTS: A force sensor was built with a flexible membrane to allow exact reference force measurements for each set of experiments. A TactiCath Quartz (TCQ) ablation catheter was brought in contact with the force sensor membrane in order to compare the TCQ force measurements to sensor reference force measurements. Measurements were performed at different tip angles (0 degrees /perpendicular contact, 45 degrees , 90 degrees /parallel contact), with fluid irrigation, different degrees of catheter deflection, and using a sheath. The accuracy of the TCQ force measurements was 0.9 +/- 0.9 g (0 degrees ), 0.8 +/- 0.8 g (45 degrees ) and 1.2 +/- 1.3 g (90 degrees ), 0.8 +/- 0.7 g (irrigation), 0.8 +/- 0.8 g (deflection), and 0.8 +/- 0.9 g (sheath); this was not significantly different among all experimental conditions. The precision was <=3.8%. CONCLUSION: CF measurements using a fiberoptic sensing technology show a high level of accuracy and precision, without being significantly influenced by tip angle, fluid irrigation, catheter deflection or use of a sheath. PMID- 27653804 TI - Models of neuromodulation for computational psychiatry. AB - Psychiatry faces fundamental challenges: based on a syndrome-based nosology, it presently lacks clinical tests to infer on disease processes that cause symptoms of individual patients and must resort to trial-and-error treatment strategies. These challenges have fueled the recent emergence of a novel field-computational psychiatry-that strives for mathematical models of disease processes at physiological and computational (information processing) levels. This review is motivated by one particular goal of computational psychiatry: the development of 'computational assays' that can be applied to behavioral or neuroimaging data from individual patients and support differential diagnosis and guiding patient specific treatment. Because the majority of available pharmacotherapeutic approaches in psychiatry target neuromodulatory transmitters, models that infer (patho)physiological and (patho)computational actions of different neuromodulatory transmitters are of central interest for computational psychiatry. This article reviews the (many) outstanding questions on the computational roles of neuromodulators (dopamine, acetylcholine, serotonin, and noradrenaline), outlines available evidence, and discusses promises and pitfalls in translating these findings to clinical applications. WIREs Cogn Sci 2017, 8:e1420. doi: 10.1002/wcs.1420 For further resources related to this article, please visit the WIREs website. PMID- 27653805 TI - ICI-RS 2015-Is a better understanding of sleep the key in managing nocturia? AB - AIMS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom. However, the applied treatment modalities do not improve symptoms in about half of the patients. The aim of this report is to generate new ideas for future nocturia research, with special emphasis on the role of sleep physiology and sleep disorders. METHODS: The following is a report of the presentations and subsequent discussion of the Nocturia Think Tank session at the annual meeting of the International Consultation on Incontinence Research Society (ICI-RS), which took place in September 2015 in Bristol. General information about the organization of the ICI-RS meeting can be found on the website "www.ici-rs.org." An overview of challenges within the existing evidence, future research ideas, and results of research with regard to nocturia and sleep were presented. RESULTS AND CONCLUSION: In order to optimize the management of nocturia and nocturnal polyuria (NP), future research has to focus on the development of unambiguous terminology regarding nocturia and NP, the role of renal function profiles and simplified frequency volume charts as guidance of individualized therapy and the role of sleep disorders such as periodic limb movements during sleep and habitual voiding as a response to awakening. Neurourol. Urodynam. 37:2048-2052, 2018. (c) 2016 Wiley Periodicals, Inc. PMID- 27653806 TI - Tumors on periorbital, axilla, and groin areas. PMID- 27653807 TI - On the Stability of Cyclophane Derivates Using a Molecular Fragmentation Method. AB - A molecular fragmentation method is used to study the stability of cyclophane derivates by decomposing the molecular energy into the molecular strain and intramolecular interaction energies. The molecular strain energies obtained by utilising the fragmentation method are in good agreement with existing experimental data. The intramolecular interaction energies calculated as the difference between the supermolecular energy and the bonded fragment energies are repulsive in the cyclophanes studied. The nature of this interaction is studied for groups of systematically extended doubled layered paracyclophane systems using the random-phase approximation (RPA), two recently developed extensions to the RPA and standard density functional theory (DFT) methods including dispersion corrections. Upon a systematic increase in conjugation the strongly repulsive intramolecular interaction energy reduces and thus leads to an increase in the stability. Finally, existing experimental and theoretical estimates of the molecular strain are compared with the results of this work. PMID- 27653808 TI - Annular Lichenoid Dermatitis of Youth: A Chronic Case Managed Using Pimecrolimus. AB - Annular lichenoid dermatitis of youth, first described in 2003, is a rare and occasionally chronic skin disease. We report a case of annular lichenoid dermatitis of youth relapsing over the course of 5 years successfully treated and maintained with topical pimecrolimus cream. PMID- 27653809 TI - Leaf anatomy mediates coordination of leaf hydraulic conductance and mesophyll conductance to CO2 in Oryza. AB - Leaf hydraulic conductance (Kleaf ) and mesophyll conductance (gm ) both represent major constraints to photosynthetic rate (A), and previous studies have suggested that Kleaf and gm is correlated in leaves. However, there is scarce empirical information about their correlation. In this study, Kleaf , leaf hydraulic conductance inside xylem (Kx ), leaf hydraulic conductance outside xylem (Kox ), A, stomatal conductance (gs ), gm , and anatomical and structural leaf traits in 11 Oryza genotypes were investigated to elucidate the correlation of H2 O and CO2 diffusion inside leaves. All of the leaf functional and anatomical traits varied significantly among genotypes. Kleaf was not correlated with the maximum theoretical stomatal conductance calculated from stomatal dimensions (gsmax ), and neither gs nor gsmax were correlated with Kx . Moreover, Kox was linearly correlated with gm and both were closely related to mesophyll structural traits. These results suggest that Kleaf and gm are related to leaf anatomical and structural features, which may explain the mechanism for correlation between gm and Kleaf . PMID- 27653810 TI - (5,6-Dihydro-1,4-dithiin-2-yl)methanol as a Versatile Allyl-Cation Equivalent in (3+2) Cycloaddition Reactions. AB - The title heterocyclic alcohol readily generates a sulfur-substituted allylic cation upon simple treatment with a protic acid, thus facilitating a synthetically useful stepwise (3+2) cycloaddition reaction pathway with a range of conjugated-olefin-type substrates. The introduction of an allyl fragment in this way provided rapid access to a variety of cyclopentanoid scaffolds. The cyclic nature of the cation precursor alcohol was shown to be instrumental for efficient cycloaddition reactions to take place, thus indicating an attractive strategy for controlling the reactivity of heteroatom-substituted allyl cations. The formal cycloaddition reaction is highly regio- and stereoselective and was also used for a short total synthesis of the natural product cuparene in racemic form through a cycloaddition-hydrodesulfurization sequence. PMID- 27653811 TI - Aging perceptions and self-efficacy mediate the association between personality traits and depressive symptoms in older adults. AB - OBJECTIVE: Personality traits have been shown to be predictors of depressive symptoms in late life. Thus, we examined whether other more modifiable sources of individual differences such as self-efficacy and self-perceptions of aging would mediate the association between personality traits and depressive symptoms in older adults. METHOD: Data were obtained from 3,507 older adult participants who took part in the 2012 Health and Retirement Study. The "Big Five" personality traits, self-efficacy, aging perceptions, and depressive symptoms were assessed. Mediation analyses tested the hypothesis that self-efficacy and aging perceptions would mediate the relationship between personality traits and depressive symptoms. RESULTS: All five personality traits were significant predictors of depressive symptoms. Neuroticism was positively associated with depressive symptoms and had the greatest effect compared with the other personality traits. There was a significant indirect effect of neuroticism, extraversion, and conscientiousness on depressive symptoms (including both mediators). The mediating effect of aging perceptions on the relationship between neuroticism and depressive symptoms was the strongest compared with self-efficacy, accounting for approximately 80% of the total indirect effect. CONCLUSION: Our results provide support for interventions aimed at improving self-perceptions related to efficacy and aging in order to reduce depressive symptoms in older adults. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27653812 TI - Mixed method systematic review: the relationship between breast cancer risk perception and health-protective behaviour in women with family history of breast cancer. AB - AIM: The aim of this study was to determine and explore the relationship between risk perception and health-protective behaviour in individuals with family history of breast cancer. BACKGROUND: Women with increased risk of breast cancer due to inherited predisposition can use health-protective behaviours to facilitate prevention or early detection of cancer. DATA SOURCES: Four scientific literature databases (CINAHL, Medline, AMED, PsychInfo) and three systematic review databases were searched. DESIGN: Mixed method systematic review. REVIEW METHODS: The systematic review of peer-reviewed literature was conducted following the method described by the Centre of Reviews and Dissemination. Research studies published in English between January 2004-December 2014 focussing on individuals with family history of breast cancer were included. Of 210 papers identified, 10 studies were eligible for inclusion. Studies were assessed for their quality. Due to the diversity of the studies, a three-step analysis was undertaken involving narrative summary of the quantitative data, thematic analysis and presentation of integrated results in narrative form. RESULTS: A clear link between breast cancer risk perception and some health protective behaviour was identified. Screening administered by health professionals (mammogram screening, chemoprevention) were appropriately adopted. However, behaviours requiring high individual input (breast self-examination, lifestyle changes) were not as appropriately adopted and the decision process was not as clearly linked to risk perception. CONCLUSIONS: There is limited understanding about the complex relationship between risk perception and health protective behaviour. Risk communication and health promotion need to be further developed to assist individuals to better engage with their actual risk and risk appropriate behaviours, particularly those that require regular personal effort. PMID- 27653813 TI - Comparison of Two Miniaturized Cardiopulmonary Bypass Systems Regarding Inflammatory Response. AB - Cardiopulmonary bypass (CPB) is a known mediator of systemic inflammatory response. Extracorporeal circulations are undergoing continuous modifications and optimizations to achieve better results. Hence we aim to compare the inflammatory response associated with two recent miniature extracorporeal circulation systems during normothermic CPB. We measured plasma levels of cytokines including interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha, migration inhibitory factor (MIF), receptor for advanced glycation endproduct, and cluster of differentiation 40 ligand in 60 consecutive patients during the first 24 h after CPB. The patients were prospectively randomized to one of three trial groups: patients in group A were operated with the minimal extracorporeal circulation circuit (MECC, Maquet, Rastatt, Germany), group B operated with the extracorporeal circulation circuit optimized (ECC.O, Sorin, Italy), and group C operated with a conventional extracorporeal circuit (CECC, Maquet). Arterial blood samples were collected at intervals before, 30 min after initiation, and after termination of CPB. Further samples were collected 6 and 24 h after CPB. IL 10 levels were significantly raised in the CECC group as compared with either of the mini ECC-circuits with a peak concentration at 6 h postoperatively. Human MIF concentrations were significantly higher in the CECC group starting 30 min after CPB and peaking at the end of CPB. The overall reduction in cytokine concentrations in the mini-ECC groups correlated with a lower need for blood transfusion in MECC and a shorter mechanical ventilation time for ECC.O. Normothermic CPB using minimally invasive extracorporeal circulation circuits can reduce the inflammatory response as measured by cytokine levels, which may be beneficial for perioperative preservation of pulmonary function and hemostasis in low risk patients. PMID- 27653814 TI - Effects of autologous platelet transfusion on platelet inhibition in ticagrelor treated and clopidogrel-treated subjects. AB - : Essentials Limited data on hemostatic benefits of platelet transfusion (PT) exist. 44 healthy subjects had a single dose of ticagrelor or clopidogrel +/- autologous PT post-dosing. PT did not reverse ticagrelor's antiplatelet effects and had minimal impact post clopidogrel. Post-ticagrelor, PT is unlikely to be beneficial, and the benefits post-clopidogrel are unknown. SUMMARY: Background Antiplatelet agents increase bleeding risk. Few data on hemostatic benefits of platelet transfusion exist. Objective To assess the effect of autologous platelet transfusion on ticagrelor-mediated and clopidogrel-mediated platelet inhibition in a single-center, open-label, randomized, cross-over study (NCT01744288). Methods Forty-four healthy subjects received ticagrelor (180 mg) or clopidogrel (600 mg; two functional CYP2C19 alleles [*1 or *17] required) with or without platelet transfusion (14-day washout). Subjects received one autologous platelet apheresis unit (approximately six pooled donor platelet units) 24 h (n = 15) or 48 h (n = 13) after ticagrelor or 48 h after clopidogrel (n = 16). Platelet apheresis was conducted 72 h before transfusion. Aspirin (81 mg per day) was taken from after apheresis until 24 h before transfusion. P2Y12 reaction units (PRUs) and inhibition of platelet aggregation (IPA) induced by ADP were measured. Results Mean age and body mass index were 30 years (standard deviation [SD] 6 years) and 26.9 kg m-2 (SD 4.0 kg m-2 ), respectively; 98% of subjects were men, and 39 of 44 completed treatment. Platelet transfusion 24 h after ticagrelor had minimal effects on IPA or PRU values within 48 h after transfusion. Platelet transfusion 48 h after ticagrelor also had minimal effects on IPA or PRU values at most post-transfusion times. Platelet transfusion 48 h after clopidogrel, versus no transfusion, had a small reversing effect on IPA (24 h, 36 h, and 48 h) and PRU values (12 h, 24 h, and 36 h) after transfusion. Conclusions Autologous platelet transfusion is unlikely to be of clinical benefit in reversing the antiplatelet effects of ticagrelor. The clinical relevance of the small effects seen with clopidogrel is unknown. PMID- 27653815 TI - Differential actigraphy for monitoring asymmetry in upper limb motor activities. AB - Most applications of accelerometry-based actigraphy require a single sensor, properly located onto the body, to estimate, for example, the level of activity or the energy expenditure. Some approaches adopt a multi-sensor setup to improve those analyses or to classify different types of activity. The specific case of two symmetrically placed actigraphs allowing, by some kind of differential analysis, for the assessment of asymmetric motor behaviors, has been considered in relatively few studies. This article presents a novel method for differential actigraphy, which requires the synchronized measurements of two triaxial accelerometers (programmable eZ430-Chronos, Texas Instruments, USA) placed symmetrically on both wrists. The method involved the definition of a robust epoch-related activity index and its implementation on-board the adopted programmable platform. Finally, the activity recordings from both sensors allowed us to define a novel asymmetry index AR24 h ranging from -100% (only the left arm moves) to +100% (only the right arm moves) with null value marking a perfect symmetrical behavior. The accuracy of the AR24 h index was 1.3%. Round-the-clock monitoring on 31 healthy participants (20-79 years old, 10 left handed) provided for the AR24 h reference data (range -5% to 21%) and a fairly good correlation to the clinical handedness index (r = 0.66, p < 0.001). A subset of 20 participants repeated the monitoring one week apart evidencing an excellent test retest reliability (r = 0.70, p < 0.001). Such figures support future applications of the methodology for the study of pathologies involving motor asymmetries, such as in patients with motor hemisyndromes and, in general, for those subjects for whom a quantification of the asymmetry in daily motor performances is required to complement laboratory tests. PMID- 27653819 TI - Dosage calculations for nurses June L Olsen Dosage calculations for nurses et al Pearson Education L14.99 312pp 9780132068840 0132068842 [Formula: see text]. AB - A COMPREHENSIVE review of dosage calculation for nursing staff, this covers accurate calculation skills and interpretation of units of measurement in the context of safe medication-administration practice. PMID- 27653817 TI - Predicting the aquatic toxicity mode of action using logistic regression and linear discriminant analysis. AB - The paper highlights the use of the logistic regression (LR) method in the construction of acceptable statistically significant, robust and predictive models for the classification of chemicals according to their aquatic toxic modes of action. Essentials accounting for a reliable model were all considered carefully. The model predictors were selected by stepwise forward discriminant analysis (LDA) from a combined pool of experimental data and chemical structure based descriptors calculated by the CODESSA and DRAGON software packages. Model predictive ability was validated both internally and externally. The applicability domain was checked by the leverage approach to verify prediction reliability. The obtained models are simple and easy to interpret. In general, LR performs much better than LDA and seems to be more attractive for the prediction of the more toxic compounds, i.e. compounds that exhibit excess toxicity versus non-polar narcotic compounds and more reactive compounds versus less reactive compounds. In addition, model fit and regression diagnostics was done through the influence plot which reflects the hat-values, studentized residuals, and Cook's distance statistics of each sample. Overdispersion was also checked for the LR model. The relationships between the descriptors and the aquatic toxic behaviour of compounds are also discussed. PMID- 27653820 TI - Tracheostomies: the complete guide Linda L Morris Tracheostomies: the complete guide and M Sherif Afifi Springer Publishing Company L59.95 384pp 97808266105172 97808266105172 [Formula: see text]. AB - The chapters of this book are well structured with easy-to-understand diagrams, and each gives a supporting conclusion and a key-points-to-remember section. PMID- 27653821 TI - The lost art of listening: how learning to listen can improve relationships Michael P Nichols The lost art of listening: how learning to listen can improve relationships Guilford Press L11.95 314pp 9781593859862 1593859864 [Formula: see text]. AB - It is good to talk, but better to talk and listen. This truism is the subject of this self-help guide, in which the author asserts that talking without listening is merely the first level of interchange. he goes on to explain what it means to listen, and differences of interpretation between men and women. PMID- 27653816 TI - Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity. AB - Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naive immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific and sex-specific. Bioinformatic analysis of the genetically controlled transcript networks reveals reduced cell type specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS (genome-wide association study candidate genes for MS susceptibility) genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared with PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T-cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease. PMID- 27653822 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27653824 TI - Simulation practice. AB - As practice placements for students become difficult to find, nurse educators increasingly turn to high-fidelity patient simulation (HFPS) programmes to enhance psychomotor and cognitive skills in controlled environments. PMID- 27653823 TI - Diary. AB - Our roundup of what's on. PMID- 27653825 TI - Temporary staff. AB - This article is based on a comparative study of the work done by temporary and permanent staff. Using non-participant observation and document analysis of interviews, data from 605 general and specialist staff, including permanent and temporary staff, were collected between 2004 and 2009. PMID- 27653826 TI - Radiographic markers. AB - Radiographic markers, which are personal to each radiographer and used with every patient, are among the most frequently handled objects in radiology departments. Radiographers who fail to clean these accessories do not consider their potential as vectors for cross-contamination. PMID- 27653827 TI - Intrabronchial valves for persistent air-leaks: what's the verdict? PMID- 27653829 TI - Postdischarge Suicides: Nightmare and Disgrace. PMID- 27653828 TI - Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot. AB - In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats. We observed insulin being released into the bloodstream after a 2 min trans cutaneous irradiation of this site by a compact LED light source. Control animals treated with the same material, but in which light was blocked from the site, showed no release of insulin into the bloodstream. We also demonstrate that additional pulses of light from the light source result in additional pulses of insulin being absorbed into circulation. A significant reduction in blood glucose was then observed. Together, these results demonstrate the feasibility of using light to allow for the continuously variable control of insulin release. This in turn has the potential to allow for the tight control of blood glucose without the invasiveness of insulin pumps and cannulas. PMID- 27653830 TI - Roll-to-Roll sputtered ITO/Cu/ITO multilayer electrode for flexible, transparent thin film heaters and electrochromic applications. AB - We fabricate high-performance, flexible, transparent electrochromic (EC) films and thin film heaters (TFHs) on an ITO/Cu/ITO (ICI) multilayer electrode prepared by continuous roll-to-roll (RTR) sputtering of ITO and Cu targets. The RTR sputtered ICI multilayer on a 700 mm wide PET substrate at room temperature exhibits a sheet resistance of 11.8 Omega/square and optical transmittance of 73.9%, which are acceptable for the fabrication of flexible and transparent EC films and TFHs. The effect of the Cu interlayer thickness on the electrical and optical properties of the ICI multilayer was investigated in detail. The bending and cycling fatigue tests demonstrate that the RTR-sputtered ICI multilayer was more flexible than a single ITO film because of high strain failure of the Cu interlayer. The flexible and transparent EC films and TFHs fabricated on the ICI electrode show better performances than reference EC films and TFHs with a single ITO electrode. Therefore, the RTR-sputtered ICI multilayer is the best substitute for the conventional ITO film electrode in order to realize flexible, transparent, cost-effective and large-area EC devices and TFHs that can be used as flexible and smart windows. PMID- 27653831 TI - Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMABTM antibody antibiotic conjugate against Staphylococcus aureus in mice. AB - DSTA4637A, a novel THIOMABTM antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as a potential therapy against S. aureus infections. Structurally, TAC is composed of an anti-S. aureus antibody linked to a potent antibiotic, dmDNA31. The goal of the current study was to characterize the pharmacokinetics (PK) of TAC in mice, assess the effect of S. aureus infection on its PK, and evaluate its pharmacodynamics (PD) by measuring the bacterial load in various organs at different timepoints following TAC treatment. Plasma concentrations of 3 analytes, total antibody (TAb), antibody-conjugated dmDNA31 (ac-dmDNA31), and unconjugated dmDNA31, were measured in these studies. In non-infected mice (target antigen absent), following intravenous (IV) administration of a single dose of TAC, systemic concentration-time profiles of both TAb and ac-dmDNA31 were bi-exponential and characterized by a short distribution phase and a long elimination phase as expected for a monoclonal antibody-based therapeutic. Systemic exposures of both TAb and ac-dmDNA31 were dose proportional over the dose range tested (5 to 50 mg/kg). In a mouse model of systemic S. aureus infection (target antigen present), a single IV dose of TAC demonstrated PK behavior similar to that in the non-infected mice, and substantially reduced bacterial load in the heart, kidney, and bones on 7 and 14 d post dosing. These findings have increased our understanding of the PK and PK/PD of this novel molecule, and have shown that at efficacious dose levels the presence of S. aureus infection had minimal effect on TAC PK. PMID- 27653833 TI - The evolution of morbidity and mortality conferences. PMID- 27653832 TI - Radiation endurance in Al2O3 nanoceramics. AB - The lack of suitable materials solutions stands as a major challenge for the development of advanced nuclear systems. Most issues are related to the simultaneous action of high temperatures, corrosive environments and radiation damage. Oxide nanoceramics are a promising class of materials which may benefit from the radiation tolerance of nanomaterials and the chemical compatibility of ceramics with many highly corrosive environments. Here, using thin films as a model system, we provide new insights into the radiation tolerance of oxide nanoceramics exposed to increasing damage levels at 600 degrees C -namely 20, 40 and 150 displacements per atom. Specifically, we investigate the evolution of the structural features, the mechanical properties, and the response to impact loading of Al2O3 thin films. Initially, the thin films contain a homogeneous dispersion of nanocrystals in an amorphous matrix. Irradiation induces crystallization of the amorphous phase, followed by grain growth. Crystallization brings along an enhancement of hardness, while grain growth induces softening according to the Hall-Petch effect. During grain growth, the excess mechanical energy is dissipated by twinning. The main energy dissipation mechanisms available upon impact loading are lattice plasticity and localized amorphization. These mechanisms are available in the irradiated material, but not in the as deposited films. PMID- 27653834 TI - Multiple introductions and onward transmission of non-pandemic HIV-1 subtype B strains in North America and Europe. AB - Most HIV-1 subtype B infections in North America and Europe seem to have resulted from the expansion of a single pandemic lineage (BPANDEMIC) disseminated from the United States (US). Some non-pandemic subtype B strains of Caribbean origin (BCAR) may have also reached North America and Europe, but their epidemiological relevance in those regions remains largely unknown. Here we analyze a total of 20,045 HIV-1 subtype B pol sequences from the US, Canada, and Europe, to estimate the prevalence and to reconstruct the spatiotemporal dynamics of dissemination of HIV-1 BCAR strains in those regions. We find that BCAR strains were probably disseminated from the Caribbean into North America and Europe at multiple times since the early 1970s onwards. The BCAR strains reached the US, Canada and at least 16 different European countries, where they account for a very low fraction (<5%) of subtype B infections, with exception of the Czech Republic (7.7%). We also find evidence of the onward transmission of BCAR clades in the US, Canada, the Czech Republic, Germany, Italy, Spain and the UK, as well as short-distance spreading of BCAR lineages between neighboring European countries from Central and Western Europe, and long-distance dissemination between the US and Europe. PMID- 27653836 TI - Mislocalisation of BEST1 in iPSC-derived retinal pigment epithelial cells from a family with autosomal dominant vitreoretinochoroidopathy (ADVIRC). AB - Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare, early-onset retinal dystrophy characterised by distinct bands of circumferential pigmentary degeneration in the peripheral retina and developmental eye defects. ADVIRC is caused by mutations in the Bestrophin1 (BEST1) gene, which encodes a transmembrane protein thought to function as an ion channel in the basolateral membrane of retinal pigment epithelial (RPE) cells. Previous studies suggest that the distinct ADVIRC phenotype results from alternative splicing of BEST1 pre mRNA. Here, we have used induced pluripotent stem cell (iPSC) technology to investigate the effects of an ADVIRC associated BEST1 mutation (c.704T > C, p.V235A) in patient-derived iPSC-RPE. We found no evidence of alternate splicing of the BEST1 transcript in ADVIRC iPSC-RPE, however in patient-derived iPSC-RPE, BEST1 was expressed at the basolateral membrane and the apical membrane. During human eye development we show that BEST1 is expressed more abundantly in peripheral RPE compared to central RPE and is also expressed in cells of the developing retina. These results suggest that higher levels of mislocalised BEST1 expression in the periphery, from an early developmental stage, could provide a mechanism that leads to the distinct clinical phenotype observed in ADVIRC patients. PMID- 27653837 TI - Preemptive kidney transplantation is associated with survival benefits among pediatric patients with end-stage renal disease. AB - Kidney transplantation is the preferred treatment for pediatric end-stage renal disease (ESRD). Preemptive transplantation avoids the increased morbidity and mortality of dialysis. Yet, previous studies have not demonstrated significant graft or patient survival benefits for children undergoing transplantation preemptively versus nonpreemptively. These previous studies were limited by small samples sizes and low rates of adverse events. Here we compared graft failure and mortality rates using Kaplan-Meier methods and Cox regression among a large national cohort of children with ESRD undergoing preemptive versus nonpreemptive kidney transplantation between 2000 and 2012. Among 7527 pediatric kidney transplant recipients in the United States Renal Data System, 1668 underwent preemptive transplantation. Over a median 4.8 years follow-up, 1314 experienced graft failure, and over a median 5.2 years of follow-up, 334 died. Dialysis exposure versus preemptive transplantation conferred a higher risk of graft failure (hazard ratio 1.32; 95% confidence interval: 1.10-1.56) and a higher risk of death (hazard ratio 1.69; 95% confidence interval: 1.22-2.33) in multivariable analysis. Compared with children undergoing preemptive transplantation, children on dialysis for >1 year had a 52% higher risk of graft failure and those on dialysis >18 months had an 89% higher risk of death, regardless of donor source. Thus, preemptive transplantation is associated with substantial benefits in allograft and patient survival among children with ESRD, particularly when compared with children who receive dialysis for >1 year. These findings support policies to promote early access to transplantation and avoidance of dialysis for children with ESRD whenever feasible. PMID- 27653839 TI - A single weekly Kt/Vurea target for peritoneal dialysis patients does not provide an equal dialysis dose for all. AB - Dialysis adequacy is traditionally based on urea clearance, adjusted for total body volume (Kt/Vurea), and clinical guidelines recommend a Kt/Vurea target for peritoneal dialysis. We wished to determine whether adjusting dialysis dose by resting and total energy expenditure would alter the delivered dialysis dose. The resting and total energy expenditures were determined by equations based on doubly labeled isotopic water studies and adjusted Kturea for resting energy expenditure and total energy expenditure in 148 peritoneal dialysis patients (mean age, 60.6 years; 97 male [65.5%]; 54 diabetic [36.5%]). The mean resting energy expenditure was 1534 kcal/d, and the total energy expenditure was 1974 kcal/day. Using a weekly target Kt/V of 1.7, Kt was calculated using V measured by bioimpedance and the significantly associated (r = 0.67) Watson equation for total body water. Adjusting Kt for resting energy expenditure showed a reduced delivered dialysis dose (ml/kcal per day) for women versus men (5.5 vs. 6.2), age under versus over 65 years (5.6 vs. 6.4), weight <65 versus >80 kg (5.8 vs. 6.1), low versus high comorbidity (5.9 vs. 6.2), all of which were significant. Adjusting for the total energy expenditure showed significantly reduced dosing for those employed versus not employed (4.3 vs. 4.8), a low versus high frailty score (4.5 vs. 5.0) and nondiabetic versus diabetic (4.6 vs. 4.9). Thus, the current paradigm for a single target Kt/Vurea for all peritoneal dialysis patients does not take into account energy expenditure and metabolic rate and may lead to lowered dialysis delivery for the younger, more active female patient. PMID- 27653840 TI - Parathyroid hormone metabolism and signaling in health and chronic kidney disease. AB - Circulating parathyroid hormone (PTH) shows a complex relationship with hard outcomes in subjects with chronic kidney disease (CKD). Moreover, intervention studies directly targeting PTH failed to yield unequivocal results. Disturbed PTH metabolism, posttranslational modifications of PTH, and end-organ hyporesponsiveness to PTH may explain the poor performance of PTH as an outcome biomarker and precise target of therapy in the setting of CKD, at least in the gray middle target zone. PTH fragments accumulate in CKD patients and may exert effects that are distinct from, if not opposite to biointact (1-84)PTH. Posttranslational modification of PTH and especially oxidation may alter the interaction of PTH with its receptor. Its clinical relevance, however, remains a matter of ongoing debate. Less controversial is the issue of end-organ hyporesponsiveness to PTH. This phenomenon, formally referred to as PTH resistance, has long been recognized in CKD, but factors and mechanisms contributing to it remain poorly defined. Subsequent evidence identified downregulation of the PTH receptor and competing downstream signals as underlying pathophysiologic mechanisms. End-organ hyporesponsiveness to PTH in CKD, along with important analytical and biological variability, renders defining the PTH target range in CKD challenging. Although this may still be accomplished at the population level, it may prove to be very difficult at the individual level. This is a disillusioning thought in an era of personalized medicine. Parallel to the search of a functional and readily available assay quantifying PTH signaling tone or sensitivity, additional biomarkers (or a panel of biomarkers) should be formally evaluated. PMID- 27653838 TI - The pathway to muscle fibrosis depends on myostatin stimulating the differentiation of fibro/adipogenic progenitor cells in chronic kidney disease. AB - Fibrosis in skeletal muscle develops after injury or in response to chronic kidney disease (CKD), but the origin of cells becoming fibrous tissue and the initiating and sustaining mechanisms causing muscle fibrosis are unclear. We identified muscle fibro/adipogenic progenitor cells (FAPs) that potentially differentiate into adipose tissues or fibrosis. We also demonstrated that CKD stimulates myostatin production in muscle. Therefore, we tested whether CKD induces myostatin, which stimulates fibrotic differentiation of FAPs leading to fibrosis in skeletal muscles. We isolated FAPs from mouse muscles and found that myostatin stimulates their proliferation and conversion into fibrocytes. In vivo, FAPs isolated from EGFP-transgenic mice (FAPs-EGFP) were transplanted into muscles of mice with CKD or into mouse muscles that were treated with myostatin. CKD or myostatin stimulated FAPs-EGFP proliferation in muscle and increased alpha smooth muscle actin expression in FAP-EGFP cells. When myostatin was inhibited with a neutralizing peptibody (a chimeric peptide-Fc fusion protein), the FAP proliferation and muscle fibrosis induced by CKD were both suppressed. Knocking down Smad3 in cultured FAPs interrupted their conversion into fibrocytes, indicating that myostatin directly converts FAPs into fibrocytes. Thus, counteracting myostatin may be a strategy for preventing the development of fibrosis in skeletal muscles of patients with CKD. PMID- 27653841 TI - Sizing nanomaterials in bio-fluids by cFRAP enables protein aggregation measurements and diagnosis of bio-barrier permeability. AB - Sizing nanomaterials in complex biological fluids, such as blood, remains a great challenge in spite of its importance for a wide range of biomedical applications. In drug delivery, for instance, it is essential that aggregation of protein-based drugs is avoided as it may alter their efficacy or elicit immune responses. Similarly it is of interest to determine which size of molecules can pass through biological barriers in vivo to diagnose pathologies, such as sepsis. Here, we report on continuous fluorescence recovery after photobleaching (cFRAP) as a analytical method enabling size distribution measurements of nanomaterials (1-100 nm) in undiluted biological fluids. We demonstrate that cFRAP allows to measure protein aggregation in human serum and to determine the permeability of intestinal and vascular barriers in vivo. cFRAP is a new analytical technique that paves the way towards exciting new applications that benefit from nanomaterial sizing in bio-fluids. PMID- 27653845 TI - In Memoriam Dr. Kenneth S. Bowers (1937-1996). PMID- 27653846 TI - In Memoriam Dr. William S. Kroger (1906-1995). PMID- 27653843 TI - Optimizing z-axis coverage of abdominal CT scans of the urinary tract: a proposed alternative proximal landmark for acquisition planning. AB - OBJECTIVE: To evaluate an alternative method to reduce the acquisition coverage of urinary tract CT. METHODS: This retrospective study included 365 abdominopelvic CT studies. Three radiographers simulated shortened acquisition coverages using three methods to determine the upper limit of the acquisition: Method 1 used the renal contours; Method 2 used the inferior margin of the 10th thoracic vertebra; and Method 3 used the point of intersection of the left diaphragmatic dome and the anterior margin of the vertebral bodies. Reductions in acquisition coverage and number of CT scans with a portion of the kidney excluded from the simulated reduced acquisition were compared between the three methods. RESULTS: The mean +/- standard deviation reduction of acquisition coverage for the three readers with Methods 1, 2 and 3 were 20.5 +/- 4.8, 15.1 +/- 6.5 and 18.2 +/- 5.3%, respectively. Compared with Method 2, Method 3 allowed a mean scan length reduction of 3.6%. The proportions of CT scans with a portion of the kidney excluded from the simulated reduced acquisition with Methods 1, 2 and 3 and averaged over the three readers were 6.7, 0.7 and 1.4%, respectively, with no significant difference between Methods 2 and 3. Interreader and intrareader agreements were excellent with all methods, but interclass correlation coefficients were higher with Method 3. CONCLUSION: The method using the renal contours should not be used owing to its high proportion of kidneys with a portion excluded from the acquisition. Using the intersection of the left diaphragmatic dome and the anterior margin of the vertebral bodies for proximal landmark for urinary tract CT represents a new alternative method with a better reduction of scan length compared with the method using the inferior margin of T10 and with no significant increase in the number of kidneys with a portion excluded from the reduced acquisition. Advances in knowledge: A new method using the point of intersection of the left diaphragmatic dome and the anterior border of the vertebral bodies on the lateral scout radiograph is introduced to reduce the z-axis coverage of urinary tract CT scans. PMID- 27653847 TI - An Invitation to Submit Letters to the Editor. PMID- 27653848 TI - An Invitation to Submit Questions Relevant to Clinical Practice for the Master Class Commentary. PMID- 27653850 TI - Editorial board page for "International Journal of Clinical and Experimental Hypnosis", Volume 44, Number 4. AB - This is a scanned image of the original Editorial Board page(s) for this issue. PMID- 27653851 TI - Central or overall obesity: which one is a better predictor of depressive symptoms in children, adolescents, and youths? AB - BACKGROUND AND PURPOSE: Despite the strong effect of central obesity on individuals' physical health outcomes, there is little evidence underlying the relationship between central obesity and mental disorders such as depression, especially in children, adolescents, and youths of the developing countries. This study explores the relationship between depressive symptoms (DS) with central and overall obesity in a sample of Iranian children, adolescents, and youths. METHODS: One thousand and fifty-two male participants ranging from 7 to 24 years old underwent standard anthropometry, and filled the DS questionnaire. RESULTS: Having controlled the potential confounders (e.g., age, socioeconomic status, pubertal maturation status, and physical activity), we found waist circumference (WC) significantly related to DS in the children (standardized beta = 0.14; P < 0.05) and adolescents (standardized beta = 0.13; P < 0.05). No significant relationship was observed between WC and DS in the youths (standardized beta = 0.09; P = 0.22). In addition, no significant relationship was observed between DS and the percentage of fat in the sampled children (standardized beta = 0.085; P = 0.13), adolescents (standardized beta = 0.10; P = 0.10), and youths (standardized beta = -0.02; P = 0.75). CONCLUSION: Central obesity (but not overall obesity) was a significant predictor of DS in the children and adolescents (7-18 years). However, DS in the youths (19-24 years) were not significantly associated with both the central and overall body obesity indices. PMID- 27653853 TI - 'Growing Old' in Shelters and 'On the Street': Experiences of Older Homeless People. AB - Homelessness among older people in Canada is both a growing concern, and an emerging field of study. This article reports thematic results of qualitative interviews with 40 people aged 46 to 75, carried out as part of a mixed-methods study of older people who are homeless in Montreal, Quebec, Canada. Our participants included people with histories of homelessness (n = 14) and persons new to homelessness in later life (n = 26). Interviews focused on experiences at the intersections of aging and homelessness including social relationships, the challenges of living on the streets and in shelters in later life, and the future. This article outlines the 5 main themes that capture the experience of homelessness for our participants: age exacerbates worries; exclusion and isolation; managing significant challenges; shifting needs and realities; and resilience, strength, and hope. Together, these findings underscore the need for specific programs geared to the unique needs of older people who are homeless. PMID- 27653852 TI - Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children. AB - BACKGROUND: Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABAB receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. CASE REPORT: We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. CONCLUSION: Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis. PMID- 27653854 TI - Patients' and healthcare providers' perceptions of a mobile portal application for hospitalized patients. AB - BACKGROUND: Hospital-based patient portals have the potential to better inform and engage patients in their care. We sought to assess patients' and healthcare providers' perceptions of a hospital-based portal and identify opportunities for design enhancements. METHODS: We developed a mobile patient portal application including information about the care team, scheduled tests and procedures, and a list of active medications. Patients were offered use of tablet computers, with the portal application, during their hospitalization. We conducted semi structured interviews of patients and provider focus groups. Text from transcribed interviews and focus groups was independently coded by two investigators using a constant comparative approach. Codes were reviewed by a third investigator and discrepancies resolved via consensus. RESULTS: Overall, 18 patients completed semi-structured interviews and 21 providers participated in three focus groups. Patients found information provided by the portal to be useful, especially regarding team members and medications. Many patients described frequent use of games and non-clinical applications and felt the tablet helped them cope with their acute illness. Patients expressed a desire for additional detail about medications, test results, and the ability to record questions. Providers felt the portal improved patient engagement, but worried that additional features might result in a volume and complexity of information that could be overwhelming for patients. Providers also expressed concern over an enhanced portal's impact on patient-provider communication and workflow. CONCLUSIONS: Optimizing a hospital-based patient portal will require attention to type, timing and format of information provided, as well as the impact on patient provider communication and workflow. PMID- 27653855 TI - SIPA1L2, MIR4697, GCH1 and VPS13C loci and risk of Parkinson's diseases in Iranian population: A case-control study. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder. Prevalence of PD increases steadily with age. A recent meta-analysis of genome wide association studies has identified six new loci to be linked with PD. Here we investigated the association of four of these new loci, SIPA1L2, MIR4697, GCH1 and VPS13C with PD in an Iranian population. Through a case-control study a total of 1800 subjects comprising 600 PD patients and 1200 unrelated healthy controls were recruited. Rs10797576, rs329648, rs11158026 and rs2414739 related to SIPA1L2, MIR4697, GCH1 and VPS13C loci respectively, were genotyped in all subjects. The difference of genotype and allele frequencies between case and control groups were investigated using chi-square test and logistic regression models with R software. Genotype and allele frequencies were significantly different in PD patients and control group for rs329648, rs11158026 and rs2414739 (p-value=0.018, 0.025, and 0.009 respectively for allele frequency differences). There was no difference in genotype nor allele frequencies between the two groups for rs10797576. We replicated the association of three new loci which are proposed for PD. More studies in other populations and also functional analysis are required to clear the role of these variants in PD. PMID- 27653856 TI - Abnormal sexuality in Parkinson's disease: fact or fancy? AB - PURPOSE: Patients with Parkinson's disease (PD) variably report sexual dysfunctions. We assessed sexuality in PD by comparing sexual function between a large group of patients with idiopathic PD and a group of subjects without PD. METHODS: We recruited 121 patients with mild-to-moderate PD (aged 40-80years) from four Italian Movement Disorder Clinics and 123 non-Parkinsonian controls (NPC) (aged 40-80years). Sexual function was assessed with four scales: the Brief Index of Sexual Functioning (BISF-M for men; BISF-W for women), the International Index of Erectile Function (IIEF), and the Female Sexual Function Index (FSFI). Both groups also underwent assessment with the Beck Depression Inventory (BDI) and the Mini Mental State Examination (MMSE), and patients were assessed with the Parkinson's Disease Questionnaire-8 (PDQ-8). RESULTS: No differences in total score were found between PD and NPC for any sexual function scale (BISF-M, BISF W, IIEF, FSFI: p>0.05). However, the Orgasm/Pleasure Domain (BISF, D5) was significantly lower in male patients than in controls. CONCLUSION: Our findings fail to confirm previous findings that PD is associated with a significant sexual impairment. NPC and patients with PD have comparable sexual function in both sexes. Thus, rather than dismissing sexual dysfunction as a normal parkinsonian symptom, physicians should refer patients to sexual medicine specialists who can investigate and discuss problems fully, diagnose possible comorbidities, and suggest appropriate treatments. PMID- 27653857 TI - Long-term effects of white matter changes on the risk of stroke recurrence after carotid artery stenting in patients with symptomatic carotid artery stenosis. AB - INTRODUCTION: Cerebral white matter changes (WMC) are associated with increased 30-day perioperative risk of stroke in patients undergoing carotid artery stenting (CAS). However, there is no data showing their impact on postoperative long-term stroke recurrence or survival. It remains unknown whether this effect is independent of classic cardiovascular risk factors or not. We tried to assess the effects of WMC on long-term stroke recurrence after CAS in patients with symptomatic carotid stenosis. METHODS: A database of patients with symptomatic carotid stenosis who had undergone CAS was sampled in a single Chinese medical center from 2007 to 2014. Copies of baseline brain imaging were analyzed by two investigators to evaluate the severity of WMC. We analyzed the association between WMC and stroke recurrence after CAS by reviewing case histories and conducting telephone interviews, with a mean follow-up time of 28months. RESULTS: 107 patients with an average age of 66years fulfilled the inclusion criteria, of which 70 were examined with CT and the remainder by MRI. In our cohort, 91.6% of the participants were male. There were 29 patients with diffuse WMC. In univariate analysis, patients with diffuse WMC had more contralateral occlusion than those with non-diffuse WMC. In patients with diffuse WMC, more stroke recurrences were observed compared with those with non-diffuse WMC (hazard ratio [HR] 3.516; 95% CI 1.176, 10.510, P=0.024). CONCLUSIONS: In patients with symptomatic carotid artery stenosis, diffuse WMC were a risk factor for stroke recurrences after CAS. Larger studies are warranted to confirm this finding and explore the potential clinical impact of WMC so as to better determine treatment strategies for patients with symptomatic carotid artery stenosis. PMID- 27653858 TI - High-sensitivity cardiac troponin T levels and risk of cerebral microbleeds in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. AB - BACKGROUND AND OBJECTIVE: Elevated high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with coronary disease and small-vessel ischemic stroke through their associations with atherosclerosis. Considering the relationship between atherosclerosis and cerebral microbleeds (CMBs), the purpose of this study was to examine associations between serum hs-cTnT levels and risk of CMBs in acute ischemic stroke patients. METHODS: This prospective study involved consecutively recruited acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease treated at a large tertiary care hospital in southwestern China. Clinico-demographic data were collected and analyzed by logistic regression to identify the relationship between serum hs-cTnT levels and CMB occurrence and location. RESULTS: In the final analysis, of 66 patients (27 males; mean age, 68.7years), 39 (59.1%) had CMBs. Hs-cTnT levels were not associated with risk of strictly lobar CMBs. However, after adjusting age, sex, current alcohol consumption, total cholesterol, hypertension, diabetes mellitus, prior antithrombotic therapy and NIHSS on admission, patients in the higher tertile were more likely to have CMBs and deep or infratentorial CMBs (P<0.05) compared with the lower hs-cTnT tertile. CONCLUSION: Hs-cTnT may be an independent predictor for the occurrence of CMBs, particularly of deep or infratentorial CMBs. This finding justifies further research into how hs-cTnT levels may contribute to CMBs and potentially other subclinical small-vessel diseases. PMID- 27653859 TI - Pallidal stimulation in dystonia affects cortical but not spinal inhibitory mechanisms. AB - BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna is an effective tool for the treatment of dystonia with possible distant effects reaching beyond the basal ganglia network. AIM: We analyzed the cortical silent period (CoSP) to test inhibitory circuits at the cortical level, and the cutaneous silent period (CuSP) and the H-reflex to test inhibitory circuits at the spinal level. METHODS: The upper limb muscles of 16 patients (9F, aged 54+/ (SD)16years) with generalized (N=9) and cervical (N=7) dystonia treated with DBS bilaterally were examined by the CoSP, CuSP and H-reflex in two states with random order: (i) in DBS ON and (ii) in DBS OFF condition two hours later, and compared with healthy controls. RESULTS: While the CuSP and H-Reflex did not differ between groups and remained unaffected by DBS, the CoSP was influenced significantly in dystonia. The CoSP onset latency was shortened (p<0.05 corrected) and the CoSP duration prolonged (p<0.01 corrected) in ON versus OFF condition. This effect was especially larger in generalized or phasic type of dystonia. Compared to healthy controls, the CoSP latency and duration became shorter in patients during the OFF condition only. CONCLUSION: The pallidal DBS did not affect the spinal inhibitory circuitry in dystonia. However, the abnormally low cortical inhibition was normalized after DBS possibly offering more efficient suppression of aberrant dystonic movements. PMID- 27653860 TI - Transcutaneous auricular vagus nerve stimulation regulates expression of growth differentiation factor 11 and activin-like kinase 5 in cerebral ischemia/reperfusion rats. AB - Growth differentiation factor 11 (GDF11), as a rejuvenation factor in heterochronic parabiosis, can increase proliferation of primary brain capillary endothelial cells (ECs). However, the angiogenic role of GDF11 in ischemia induced brain injury is still unclear. There are no previous reports on the spatiotemporal expression of GDF11 in cerebral ischemia/reperfusion (I/R) rats. Our recent work has strongly suggested that transcutaneous auricular vagus nerve stimulation (ta-VNS) reduces infarct size and induces angiogenesis in focal cerebral I/R rats. This study focused on expression of GDF11 and activin-like kinase 5 (ALK5) and the effects of ta-VNS in a rat cerebral I/R model. For ta VNS, electrical stimulation of the left cavum concha (1h duration) using percutaneous needles was initiated 30min after induction of ischemia. Expression of GDF11 was analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, real-time polymerase chain reaction, and western blot 24h, 3d, and 7d after reperfusion. In addition, neurobehavioral function, EC proliferation, and expression of ALK5 in ECs in the peri-infarct cortex were measured. Results showed that levels of GDF11 were significantly elevated after cerebral I/R, both in plasma and the peri-infarct cerebral cortex. Interestingly, splenic GDF11 levels decreased after ischemia. ALK5 was expressed in ECs in the peri-infarct cerebral cortex where active vessel remodeling was noted. ta-VNS improved neurobehavioral recovery, upregulated cerebral GDF11 and downregulated splenic GDF11, indicating a brain-spleen communication during stroke. ta-VNS also increased expression of ALK5 in ECs and stimulated proliferation of ECs. These results suggest that, after cerebral ischemia, GDF11 redistributes and participates in angiogenesis as an angiogenic factor that acts at least in part through ALK5. GDF11/ALK5 may represent a new potential therapy target for stroke. PMID- 27653861 TI - Interleukins 17 and 10 in a sample of Egyptian relapsing remitting multiple sclerosis patients. AB - BACKGROUND: Cytokines are major contributors in the immune disruption in multiple sclerosis (MS). OBJECTIVE: Evaluating the proinflammatory (IL-17A) and anti inflammatory (IL-10) cytokines in relapsing-remitting (RR) MS patients at time of relapse and during remission. SUBJECTS AND METHOD: A case-control study including 30 RRMS patients and 15 controls. Patients were recruited from the Kasr Al-Ainy MS research unit (KAMSU), Cairo University, Egypt. Levels of IL-17A and IL-10 were assessed in patients' sera, during relapse and 30days after IV methylprednisolone, and in control subjects using enzyme linked immunosorbent assays (ELISA). RESULTS: IL-17 was higher in patients during relapse and remission phases when compared with controls (P=0.001), whereas, IL-10 was higher in patients during remission but normal during relapse (P=0.01; 0.86 respectively). IL-17 increased during relapses (P=0.001) while IL-10 increased during remissions (P=0.028). No significant correlations were found between both interleukins and age at onset; disease duration, number of relapses; or EDSS. CONCLUSION: RRMS patients can have a regulatory imbalance between both pro-and antiinflammatory cytokines, which could be a target for treatment strategies rather than focusing on a single cytokine. PMID- 27653862 TI - Polymorphisms in exon 2 of CD1 genes are associated with susceptibility to Guillain-Barre syndrome. AB - Guillain-Barre syndrome (GBS) is a post-infectious autoimmune peripheral neuropathy. Studies have shown that a T cell-mediated immune response to peripheral nerve is associated with the pathogenesis of GBS. CD1 molecules are MCH-like glycoproteins specialized to capture and present glycolipids to T cells. Polymorphisms of CD1 genes may affect susceptibility to GBS. We investigated the polymorphisms of CD1 genes in GBS patients in a Chinese Han population. In 126 patients and in 138 controls we genotyped exon 2 of the CD1A and CD1E genes. The results indicated that polymorphisms of CD1A genes are associated with GBS. Furthermore, subjects with CD1A*01/02 had a 2.9 times lower risk of developing GBS, and those with CD1A*02/02 had a 2.5 times higher risk to developing GBS than the controls, while there was no association between polymorphisms of CD1E genes and the susceptibilities to GBS. PMID- 27653863 TI - Clinical classification of 103 Japanese patients with Guillain-Barre syndrome. AB - Guillain-Barre syndrome (GBS) is the commonest cause of flaccid paralysis worldwide. Miller Fisher syndrome (MFS) is a variant of GBS characterized by ophthalmoplegia and ataxia. Together GBS and MFS form a continuum of discrete and overlapping subtypes, the frequency of which remains unknown. We retrospectively analysed the clinical features (antecedent symptoms, pattern of neurological weakness or ataxia, presence of hypersomnolence) of 103 patients at a single hospital in Japan. Patients were then classified according to new diagnostic criteria (Wakerley et al., 2014). Laboratory data (neurophysiology and anti ganglioside antibody profiles) were also analysed. According to the new diagnostic criteria, the 103 patients could be classified as follows: classic GBS 73 (71%), pharyngeal-cervical-brachial weakness 2 (2%), acute pharyngeal weakness 0 (0%), paraparetic GBS 1 (1%), bifacial weakness with paraesthesias 1 (1%), polyneuritis cranialis 0 (0%), classic MFS 18 (17%), acute ophthalmoparesis 1 (1%), acute ptosis 0 (0%), acute mydriasis 0 (0%), acute ataxic neuropathy 1 (1%), Bickerstaff brainstem encephalitis 3 (3%), acute ataxic hypersomnolence 0 (0%), GBS and MFS overlap 1 (1%), GBS and Bickerstaff brainstem encephalitis overlap 1 (1%), MFS and pharyngeal-cervical-brachial weakness overlap 1 (1%). Application of the new clinical diagnostic criteria allowed accurate retrospective diagnosis and classification of GBS and MFS subtypes. PMID- 27653864 TI - Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT. AB - OBJECTIVE: Orolingual angioedema (OA) is a well known early complication of treatment with alteplase in ischemic stroke patients. Our aim was to study risk factors for OA in these patients, namely insular cortex ischemia. METHODS: Retrospective case-cohort study using the prospective registry of all consecutive ischemic stroke patients submitted to intravenous thrombolysis with alteplase. Clinical data was retrieved from the registry and medical records. Two independent observers evaluated early signs of insular cortex ischemia on pre thrombolysis computed tomography (CT) and of insular cortex infarct on early follow-up imaging. Univariate and multivariate analysis were performed to identify predictors of OA. RESULTS: Of the 659 patients with acute ischemic stroke treated with alteplase, 32 developed OA (4.9%, 95%CI=3.3-6.6). Frequency of early signs of insular cortex ischemia on pre-thrombolysis CT and of insular cortex infarct on follow-up imaging was similar in patients with and without OA (p=0.241 and p=0.145, respectively). The only independent predictors of OA occurrence were female sex (OR=5.47, 95%CI=1.98-15.10) and angiotensin-converting enzyme inhibitor (ACE-I) use (OR=3.87, 95%CI=1.71-8.75). CONCLUSIONS: Female sex and ACE-I use are independent risk factors for OA occurrence in ischemic stroke patients treated with alteplase. Early signs of insular cortex ischemia on pre thrombolysis CT were not significantly associated with OA. PMID- 27653865 TI - Newly diagnosed ganglioglioma in an adult patient with multiple sclerosis. PMID- 27653866 TI - Dravet syndrome with autism inherited from a paternal mosaic heterozygous mutation on SCN1A. PMID- 27653867 TI - Does mild cognitive impairment always lead to dementia? A review. AB - Mild cognitive impairment (MCI) has often been studied in its association with dementia, yet higher rates of reversion to normal cognition than progression to dementia suggest that MCI does not necessarily lead to dementia. Compared to the numerous studies on MCI progression, relatively few have examined reversion. This paper highlights the current literature on characteristics and predictive factors of MCI reversion, along with an overview of studies on MCI patients who remain diagnostically stable (i.e., MCI stability). Of the available studies, predictors of reversion have been noted in areas of cognitive/global functioning, demographic/genetic/biomarker data, and personality/lifestyle factors. However, there is a need for increased study of MCI reversion, considering that patients in this group can fluctuate between different trajectories of MCI (e.g., normal cognition back to MCI or even progression to dementia) within a given follow-up time period. Further examination of reversion via a longitudinal, multifactorial approach would better inform clinicians regarding the likelihood of reversion amongst MCI patients and subsequently modify treatment methods accordingly. Furthermore, researchers would have greater power in detecting treatment effects in their clinical intervention studies of early dementia by improving selection criteria to exclude MCI participants who are more likely to revert and remain cognitively normal than progress to a dementia. PMID- 27653868 TI - Biomarkers of migraine: Part 1 - Genetic markers. AB - BACKGROUND: Migraine is a multifactorial socially significant disease affecting the peripheral and central nervous system. The diagnosis of "migraine" is still the only clinical, and additional methods of inspection are only required to avoid secondary headaches if certain "signs of danger". Accordingly, the search for biomarkers of migraine, confirming the diagnosis, rather than refuting others, is the leading vector in this scientific field. AIM: In this paper we have analyzed the literature data on the genetic markers associated with migraine. METHODS: List of genes was compiled using Pathway Studio 10(r) software and abstract database ResNet12 (r) made by Elsevier. Addition search (last time on 15 March 2016) was performed by using PubMed or TargetInsights. Information about 185 polymorphic loci in 98 genes associated with migraine was extracted and described. RESULTS: The genes associated with migraine could be classified into 8 major groups: homeostasis of blood vessels - 26.5%, metabolism of neurotransmitters - 11.2%, transport and reception of neurotransmitters - 24.5%, neurogenesis - 5.1%, inflammation - 8.2%, sex hormones - 5.1%, ion channels and membrane potential - 11.2%, other - 8.2%. CONCLUSION: These findings parallel the range of mechanisms implicated in migraine pathogenesis. PMID- 27653869 TI - Subacute lesion volume as a potential prognostic biomarker for acute ischemic stroke after intravenous thrombolysis. AB - BACKGROUND: The aim of this study was to identify whether subacute diffusion weighted imaging (DWI) lesion volume could predict long-term outcome in patients who had undergone intravenous thrombolysis. METHOD: Patients underwent DWI at baseline and 7days after thrombolysis. Outcomes included complete independence (modified Rankin scale [mRS] score 0 to 1), unfavorable outcome (mRS score 4 to 6) at 90days, and mortality within 90days. Multivariate logistic regression analysis was used to identify outcome predictors. RESULTS: Of 164 patients, 72 patients (43%) achieved complete independence. Poor outcomes were observed in 45 patients (27%) with an unfavorable outcome and 10 patients (6%) who died. Subacute DWI lesion volume was 3.4mL (interquartile range, 1.1-11.6) in patients with complete independence, 90.1mL (23.8-180.2) in patients with unfavorable outcome and 155.5mL (78.4-377.5) in patients who died. In multivariate logistic regression analysis, subacute DWI lesion volume was an independent predictor of complete independence (odds ratio [OR], 0.939; 95% confidence interval [CI], 0.914-0.965; p<0.001), unfavorable outcome (OR, 1.023; 95% CI, 1.014-1.033; p<0.001), and mortality (OR, 1.016; 95% CI, 1.005-1.028; p=0.005). CONCLUSION: Subacute DWI lesion volume is a critical determinant of 90-day functional outcome and mortality after thrombolysis. PMID- 27653870 TI - Usage of SWI (susceptibility weighted imaging) acquired at 7T for qualitative evaluation of temporal lobe epilepsy patients with histopathological and clinical correlation: An initial pilot study. AB - OBJECTIVES: Ultra high field MRI at 7T is able to provide much improved spatial and contrast resolution which may aid in the diagnosis of hippocampal abnormalities. This paper presents a preliminary experience on qualitative evaluation of 7T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology. METHODS: 7T ultra high field MRI data, using T1 weighted, T2*-weighted and susceptibility-weighted images (SWI), were acquired for 13 patients with drug resistant temporal lobe epilepsy (TLE) during evaluation for potential epilepsy surgery. Qualitative evaluation of the imaging data for scan quality and presence of hippocampal and temporal lobe abnormalities were scored while blinded to the clinical data. Correlation of imaging findings with the clinical data was performed. Blinded evaluation of 1.5T scans was also performed. RESULTS: On the 7T MRI findings, eight out of 13 cases demonstrated concordance with the clinically suspected TLE. Among these concordant cases, three exhibited supportive abnormal 7T MRI findings which were not detected by the clinical 1.5T MRI. Of the ten cases that progressed to epilepsy surgery, seven showed concordance between 7T MRI findings and histopathology; of these, four cases had hippocampal sclerosis. SWI had the highest concordance with the clinical and histopathological findings. Similar clinical and histopathological concordance was found with 1.5T MRI. CONCLUSIONS: There was moderate and high concordance between the 7T imaging findings with the clinical data and histopathology respectively. PMID- 27653871 TI - Oriented growth of rat Schwann cells on aligned electrospun poly(methyl methacrylate) nanofibers. AB - Transplanted Schwann cells have the potential to serve as a support for regenerating neurites after spinal cord injury. However, implanted Schwann cells die off rapidly once transplanted partly owing to the absence of a proper matrix support, with a glia scar and a cavity being present instead at the injury site. For this report, we evaluated aligned electrospun poly(methyl methacrylate) nanofibers as a Schwann cell-loading scaffold in vitro. By monitoring the fluorescence of green fluorescence protein-containing Schwann cells cultured on nanofibers, we found that aligned nanofibers provided better support for the cells than did non-aligned nanofibers. The cells elongated along the long axes of the aligned nanofibers and formed longer cell processes than when the substrate was non-aligned nanofibers. By coculturing Schwann cells with dorsal root ganglion neurons, it was also found that Schwann cells and neurites of dorsal root ganglion neurons could share and both elongate along the orientation of aligned nanofibers and thus they had a higher chance of colocalization than cocultured on film and non-aligned fibers, which might be beneficial to the ensuring process of myelination. The results of the study indicate that aligned electrospun nanofibers may serve as a Schwann cell-loading scaffold for future implantation research. PMID- 27653872 TI - Vibration training improves disability status in multiple sclerosis: A pretest posttest pilot study. AB - The purpose of this study was to examine the effects of an 8-week vibration training program on changing the disability level in people with multiple sclerosis (MS). Twenty-five adults with clinically-confirmed MS underwent an 8 week vibration training on a side-alternating vibration platform. The vibration frequency and peak-to-peak displacement were set at 20Hz and 2.6mm, respectively. Prior to and following the training course, the disability status was assessed for all participants characterized by the Patient Determined Disability Steps (PDDS) and MS Functional Composite (MSFC) scores. The training program significantly improved the PDDS (3.66+/-1.88 vs. 3.05+/-1.99, p=0.009) and the MSFC scores (0.00+/-0.62 vs 0.36+/-0.68, p<0.0001). All three MSFC components were improved: lower extremity function (9.37+/-4.92 vs. 8.13+/-4.08s, p=0.011), upper extremity function (dominant hand: 27.81+/-5.96 vs. 26.20+/-5.82s, p=0.053; non-dominant hand: 28.47+/-7.40 vs. 27.43+/-8.33s, p=0.059), and cognitive function (30.55+/-13.54 vs. 36.95+/-15.07 points, p=0.004). Our findings suggested that vibration training could be a promising alternative modality to reduce the disability level among people with MS. PMID- 27653873 TI - Characteristics of mild cognitive impairment tending to convert into Alzheimer's disease or dementia with Lewy bodies: A follow-up study in a memory clinic. AB - AIM: To determine characteristics of MCI that can predict whether patients will go on to develop AD or DLB. METHODS: Ninety-three patients diagnosed with MCI underwent neuropsychological and neuroimaging examinations, and were followed-up for a mean of 44.9+/-19.3months. They were divided into four MCI subtypes (amnestic/non-amnestic MCI, single/multiple domain) according to neuropsychological findings, and into three other MCI categories (AD-type PET, DLB-type PET, and unknown-type PET) based on (18)F-fluorodeoxyglucose PET findings. Patients who were eventually diagnosed with AD, DLB, other dementia, or remained MCI were analyzed in relation to the groups to which they had initially been allocated at the MCI stage. RESULTS: Clinical diagnosis after follow-up determined AD in 21 patients (22.6%), DLB in 12 patients (12.9%), other dementia in 2 patients (2.2%), and non-converter in 58 patients (62.3%). Amnestic single domain MCI and AD-type PET tended to convert into AD. Amnestic multiple-domain MCI and DLB-type PET tended to convert into DLB. A few patients with AD-type PET later developed DLB, and some with DLB-type PET later developed AD. CONCLUSIONS: Predicting which type of dementia a person with MCI will later develop might be possible based on early assessment with clinical symptoms in conjunction with neuropsychological and (18)F-fluorodeoxyglucose PET findings. PMID- 27653874 TI - NS1619 regulates the expression of caveolin-1 protein in a time-dependent manner via ROS/PI3K/PKB/FoxO1 signaling pathway in brain tumor microvascular endothelial cells. AB - NS1619, a calcium-activated potassium channel (Kca channel) activator, can selectively and time-dependently accelerate the formation of transport vesicles in both the brain tumor capillary endothelium and tumor cells within 15min of treatment and then increase the permeability of the blood-brain tumor barrier (BTB). However, the mechanism involved is still under investigation. Using a rat brain glioma (C6) model, the expression of caveolin-1, FoxO1 and p-FoxO1 protein were examined at different time points after intracarotid infusion of NS1619 at a dose of 30MUg/kg/min. Internalization of Cholera toxin subunit (CTB) labeled fluorescently was monitored by flow cytometry. The expression of caveolin-1 and FoxO1 protein at tumor microvessels was enhanced and caveolae-mediated CTB endocytosis was increased by NS1619 infusion for 15min. Compared with the 15min group, the expression of caveolin-1 protein was significantly decreased and the level of phosphorylation of FoxO1 was significantly increased in the NS1619 2h group. In addition, inhibitors of reactive oxygen species (ROS) or PI3K or PKB significantly attenuated the level of FoxO1 phosphorylation and also increased the expression of caveolin-1 protein in Human Brain Microvascular Endothelial Cells (HBMECs) cocultured with human glioma cells (U87) 2h after NS1619 treatment. This led to the conclusion that NS1619-mediated transport vesicle increase is, at least partly, related to the ROS/PI3K/PKB/FoxO1 signaling pathway. PMID- 27653875 TI - Callosal disconnection syndrome after ischemic stroke of the corpus callosum due to meningococcal meningitis: A case report. PMID- 27653876 TI - Lobar intracerebral haematomas: Neuropathological and 7.0-tesla magnetic resonance imaging evaluation. AB - BACKGROUND AND PURPOSE: The Boston criteria for cerebral amyloid angiopathy (CAA) need validation by neuropathological examination in patients with lobar cerebral haematomas (LCHs). In "vivo" 1.5-tesla magnetic resonance imaging (MRI) is unreliable to detect the age-related signal changes in LCHs. This post-mortem study investigates the validity of the Boston criteria in brains with LCHs and the signal changes during their time course with 7.0-tesla MRI. MATERIALS AND METHODS: Seventeen CAA brains including 26 LCHs were compared to 13 non-CAA brains with 14 LCHs. The evolution of the signal changes with time was examined in 25 LCHs with T2 and T2* 7.0-tesla MRI. RESULTS: In the CAA group LCHs were predominantly located in the parieto-occipital lobes. Also white matter changes were more severe with more cortical microinfarcts and cortical microbleeds. On MRI there was a progressive shift of the intensity of the hyposignal from the haematoma core in the acute stage to the boundaries later on. During the residual stage the hyposignal mildly decreased in the boundaries with an increase of the superficial siderosis and haematoma core collapse. CONCLUSIONS: Our post-mortem study of LCHs confirms the validity of the Boston criteria for CAA. Also 7.0 tesla MRI allows staging the age of the LCHs. PMID- 27653877 TI - Elevated cerebrospinal fluid levels of thrombospondin-1 correlate with adverse clinical outcome in patients with aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Thrombospondin-1 (TSP-1) is a homotrimeric glycoprotein which modulates a wide range of biological functions. Elevated level of TSP-1 in plasma was reported to be correlated with intracerebral hemorrhage. Our study was designed to investigate the relationship between cerebrospinal fluid (CSF) TSP-1 levels and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: CSF TSP-1 levels were measured in 31 aSAH patients on days 1-3, days 5-7 and days 8-10 after aSAH onset using enzyme-linked immunosorbent assay. Patients were under a close follow-up until death or completion of three months after aSAH. Binary logistic regression analyses were performed to determine independent risk factors for the clinical outcomes. RESULTS: TSP-1 levels peaked on days 1-3 after aSAH, kept up high on days 5-7 and remained elevated until days 8-10 (p<0.05). Significant elevation of CSF TSP-1 levels were found in patients both with and without vasospasm. Modified Rankin Scale at 3months after aSAH showed a significant correlation with CSF TSP-1 levels on days 1-3 and days 5-7 (both p<0.01). Binary logistic regression analysis showed that higher TSP-1 level on days 1-3 (p<0.05) and on days 5-7 (p<0.05) was a predictive marker of cerebrovasospasm and poor outcome of patient with aSAH. CONCLUSIONS: Upregulation of TSP-1 may involve in the pathological process of aSAH and might be a risk factor of future adverse prognosis of aSAH. PMID- 27653878 TI - Delayed iron deposit and atrophy of the putamen in a case with osmotic demyelination syndrome. PMID- 27653879 TI - Comparison of neuropsychological profiles in patients with Alzheimer's disease and mixed dementia. AB - OBJECTS: We designed this study to extensively compare the neuropsychological profiles of Alzheimer's disease (AD) and mixed dementia (MD) in a large multicenter cohort of patients. Specifically, we performed subgroup analyses to examine group differences associated with dementia severity. METHODS: A total of 1021 AD patients and 577 MD patients were included from the Clinical Research Center for Dementia of South Korea (CREDOS) Study. All patients underwent comprehensive neuropsychological and functional ratings, as well as complete physical and neurological examinations. To avoid floor confounds, only patients with Clinical Dementia Rating (CDR) scores of 0.5-2.0 were included. RESULTS: Overall, MD patients showed worse performance in frontal/executive function than those with AD. Stratification by dementia severity revealed a significant difference in global cognitive function scores between AD and MD patients only in the low severity groups (CDR 0.5). Also, MD patients showed worse performance in frontal/executive function domains in the CDR 0.5 groups whereas they had better performance in the memory domain in the CDR 1 groups than did AD patients. Additionally, AD patients showed better performance than MD patients with respect to activities of daily living at CDR levels 0.5 and 1. All differences had disappeared at the CDR 2 level of global dementia severity. CONCLUSION: This study suggests that there are significant differences in neuropsychological profiles between AD and MD patients, with the pattern of this difference varying distinctively according to dementia severity. PMID- 27653880 TI - Severe articular and musculoskeletal pain: An unexpected side effect of dimethyl fumarate therapy for multiple sclerosis. PMID- 27653881 TI - Computational models and motor learning paradigms: Could they provide insights for neuroplasticity after stroke? An overview. AB - Computational approaches for modelling the central nervous system (CNS) aim to develop theories on processes occurring in the brain that allow the transformation of all information needed for the execution of motor acts. Computational models have been proposed in several fields, to interpret not only the CNS functioning, but also its efferent behaviour. Computational model theories can provide insights into neuromuscular and brain function allowing us to reach a deeper understanding of neuroplasticity. Neuroplasticity is the process occurring in the CNS that is able to permanently change both structure and function due to interaction with the external environment. To understand such a complex process several paradigms related to motor learning and computational modeling have been put forward. These paradigms have been explained through several internal model concepts, and supported by neurophysiological and neuroimaging studies. Therefore, it has been possible to make theories about the basis of different learning paradigms according to known computational models. Here we review the computational models and motor learning paradigms used to describe the CNS and neuromuscular functions, as well as their role in the recovery process. These theories have the potential to provide a way to rigorously explain all the potential of CNS learning, providing a basis for future clinical studies. PMID- 27653882 TI - Transcranial magnetic stimulation combined with upper-limb training for improving function after stroke: A systematic review and meta-analysis. AB - BACKGROUND: Several neuromodulation treatments have been developed, and their effects have been studied in recent years in order to improve neurological rehabilitation after a stroke. The association between upper-limb training and repetitive transcranial magnetic stimulation (rTMS) has provoked controversies and produced inconclusive results. OBJECTIVE: The purpose of this study was to investigate the effects of rTMS combined with upper-limb training versus sham rTMS combined with upper-limb training on the upper-limb recovery after a stroke. METHODS: A systematic review with meta-analysis was performed. The eligible studies were randomized controlled trials with stroke subjects, and the outcomes were related to upper-limb motor/functional status and spasticity. RESULTS: A total of 3234 citations were identified, and 11 studies were included. The meta analysis included eight studies with 199 participants and did not show any difference between groups, neither for upper-limb function nor for spasticity (upper-limb function [0.03 (95% CI: -0.25 to 0.32; I(2) 0%)] and Modified Ashworth Scale [-0.31 (95% CI: -0.78 to 0.17; I(2) 43%)]). CONCLUSION: The current state of the literature is not enough to support the hypothesis that a combination of rTMS and upper-limb training has a stronger effect on upper-limb function than upper-limb training alone. PMID- 27653884 TI - Changes in effective connectivity of sensorimotor rhythms in thalamocortical circuits during the induction and recovery of anesthesia in mice. AB - The thalamocortical network serves a role in both consciousness and sensorimotor processing. However, little is known regarding how changes in conscious states, via induction of and recovery from anesthesia, affect the processing of sensorimotor information in the thalamocortical network. To address this, we investigated the dynamics of causal interactions among sensorimotor rhythms (SMR; frequency range of 3-12Hz) across the thalamocortical network during transitions into and out of ketamine-induced unconsciousness. Two local field potentials from the ventral lateral and ventrobasal thalamic nuclei, as well as two intracranial electroencephalography signals from the primary sensory and primary motor regions, were recorded in 10 mice. Spectral Granger causality analysis revealed two distinct frequency-specific patterns in sensorimotor rhythms. For the low frequency (3-6.5Hz) SMR, loss of consciousness evoked causal influences directed from the cortex to the thalamus. For the high-frequency (6.5-12Hz) SMR, causal influences from the primary sensory cortex to other regions during the conscious period were abruptly altered by loss of consciousness and gradually regenerated following recovery of consciousness. The results of the present study indicate that anesthesia alters the flow of sensorimotor information in the thalamocortical network and may provide evidence of the neural basis of loss and recovery of sensorimotor function associated with anesthesia. PMID- 27653883 TI - Epidemiology and prognostic factors of inpatient mortality of Guillain-Barre syndrome: A nationwide population study over 14years in Asian country. AB - OBJECTIVE: The present study aimed to evaluate the characteristics of inpatient mortality from Guillain-Barre syndrome (GBS), which is a rare and potentially life-threatening polyradiculoneuropathy, in an Asian country, as there are few big-data studies regarding this topic. METHODS: We obtained data regarding patients with GBS from Taiwan's National Health Insurance Research Database admission records. We identified patients with a discharge diagnosis of GBS during 2000-2013 using the International Classification of Diseases, 9th Revision, Clinical Modification code (357.0), and evaluated their baseline characteristics, clinical complications, and risk factors. RESULTS: We identified 5469 patients with GBS, and the crude incidence of GBS was 1.71 per 100,000 person-years. The inpatient mortality rate was 1.61% (88/5469) and 55 deaths (62.5% of all deaths) occurred before day 19 of the hospitalization (mainly during the progressive phase). The predictors of inpatient mortality included older age, a greater comorbidity burden (especially catastrophic illness), endotracheal intubation, mechanical ventilation, cardiac complications, and systemic infection. In contrast, patients who were admitted to a medical center or Neurology Department exhibited a higher survival rate. CONCLUSIONS: This 14 year nationwide study included the largest analysis of Asian patients with GBS to date, and identified various prognostic factors that predicted inpatient mortality. PMID- 27653885 TI - Characteristic lesion pattern and echocardiographic findings in extra-cardiac shunt-related stroke. AB - Among embolic strokes of undetermined source, under-recognized etiology such as extra-cardiac shunt could be a potential risk factor. We sought to characterize infarction patterns on diffusion-weighted imaging (DWI) and transesophageal echocardiography (TEE) findings in extra-cardiac shunt-related stroke. We enrolled 96 consecutive patients with cryptogenic stroke who had an extra- or intra-cardiac shunt. Diagnosis of the shunt was performed using TEE with agitated saline contrast and pulmonary vein isolation. Infarction patterns on DWI and total lesion volume were analyzed. Bubble amounts through the shunt were classified via the International Consensus Criteria (ICC). Short-term prognosis, patterns and size of DWI lesions, and involved vascular territories were not significantly different between two groups. Multivariate analysis revealed that extra-cardiac shunt group has a smaller total infarct volume (odds ratio [OR]=0.427, 95% confidence interval [95% CI] 0.228-0.799, p=0.008), and significantly higher bubble grade during resting state and lower grade during the Valsalva maneuver (OR= 0.539, 95% CI 0.438-0.663, p<0.001). Stroke related to an extra-cardiac shunt presented smaller infarct volume, favorable clinical outcomes and characteristic finding on TEE with agitated saline contrast. Further study is needed to confirm whether the extra-cardiac shunt is an independent risk factor. PMID- 27653886 TI - Adult moyamoya-atherosclerosis syndrome: Clinical and vessel wall imaging features. AB - INTRODUCTION: We sought to incorporate high-resolution magnetic resonance imaging (HRMRI) into the diagnostic process of intracranial atherosclerosis associated moyamoya syndrome in adult patients. METHODS: From March 2013 to March 2014, HRMRI was consecutively performed on adult patients with angiographic moyamoya. The patients were classified as moyamoya - plaques (MMD-P) if a plaque could be identified or as moyamoya - no plaques (MMD-NP) if a plaque could not be identified. The angiography, HRMRI findings and atherogenic risk factors of these patients were analyzed. RESULTS: Fifty-one patients (mean age 39+/-9, 20 males) were enrolled. On traditional angiography, probable intracranial atherosclerosis was identified in 5 patients, no definite diagnosis in 12 patients, and moyamoya disease in 34 patients. On HRMRI, 15 out of 32 patients with risk factors and 4 out of 19 patients without risk factors were found to have plaques and were diagnosed as MMD-P, while the other 32 patients were diagnosed as MMD-NP. The MMD P patients were more likely to be older (P=0.033) and male (P=0.0353) and were less likely to have cerebral hemorrhage (P=0.0066) and a history of disease progression (P=0.0012). CONCLUSIONS: Our study suggests that HRMRI can help diagnose intracranial atherosclerosis more accurately in moyamoya disease patients with atherogenic risk factors. The distinct clinical features between MMD-P and MMD-NP patients suggest different underlying pathophysiology and therefore potentially different treatment strategies. PMID- 27653887 TI - At-home tDCS of the left dorsolateral prefrontal cortex improves visual short term memory in mild vascular dementia. AB - OBJECTIVES: Previous studies have shown that anodal transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) led to an improvement of various cognitive functions in patients with Alzheimer dementia, early affected by short-term memory deficits. Since this approach has not been evaluated in the context of vascular dementia, which rather affects the velocity of cognitive responses, we aimed at improving these functions by applying repetitive sessions of anodal tDCS. METHODS: Four 20-minute sessions of 2mA anodal or sham at-home tDCS were applied to the left DLPFC in a single-blinded randomised study of 21 patients with mild vascular dementia, with parallel-group design. The effect of tDCS on cognitive testing was assessed up to two weeks beyond the stimulation time. RESULTS: A similar clinically meaningful improvement of various cognitive and behavioral dysfunction characteristics could be observed following either active or sham tDCS, whereas visual recall, and reaction times in the n-back task as well as in the go/no-go test improved only in the active tDCS group. CONCLUSIONS: In patients with mild vascular dementia, anodal tDCS of the left DLPFC is able to produce additional effects to cognitive training on visual short-term memory, verbal working memory, and executive control. PMID- 27653888 TI - Environmental, dietary and case-control study of Nodding Syndrome in Uganda: A post-measles brain disorder triggered by malnutrition? AB - Nodding Syndrome (NS) is an epileptic encephalopathy characterized by involuntary vertical head nodding, other types of seizures, and progressive neurological deficits. The etiology of the east African NS epidemic is unknown. In March 2014, we conducted a case-control study of medical, nutritional and other risk factors associated with NS among children (aged 5-18years) of Kitgum District, northern Uganda (Acholiland). Data on food availability, rainfall, and prevalent disease temporally related to the NS epidemic were also analyzed. In NS Cases, the mean age of reported head nodding onset was 7.6years (range 1-17years). The epidemiologic curve of NS incidence spanned 2000-2013, with peaks in 2003 and 2008. Month of onset of head nodding was non-uniform, with all-year-aggregated peaks in April and June when food availability was low. Families with one or more NS Cases had been significantly more dependent on emergency food and, immediately prior to head nodding onset in the child, subsistence on moldy plant materials, specifically moldy maize. Medical history revealed a single significant association with NS, namely prior measles infection. NS is compared with the post measles disorder subacute sclerosing panencephalitis, with clinical expression triggered by factors associated with poor nutrition. PMID- 27653889 TI - Disease activity in chronic inflammatory demyelinating polyneuropathy. AB - INTRODUCTION: Evaluation of disease status in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is often done by a combination of clinical evaluation and electrodiagnostic studies. A CIDP disease activity status (CDAS) was developed to standardize outcomes in CIDP patients. We aimed to determine if the CDAS was concordant with classical evaluation and whether CDAS enables benchmarking of CIDP. METHODS: We performed a retrospective chart review of 305 CIDP patients and identified 206 patients with >1 visit and applied the CDAS to this cohort. We examined relationships between the CDAS and classical evaluation as to outcomes and compared our cohort to other CIDP cohorts who had CDAS. RESULTS: We found that the CDAS mirrored disease severity as measured by electrophysiology and vibration perception thresholds in that CDAS class 5 had more severe neuropathy. Our results are similar to other cohorts in the middle CDAS strata with the exception of fewer subjects in CDAS 1 and more in CDAS 5. The only demographic factor predicting CDAS 5 in our cohort was age, and the overall treatment response rate using the CDAS classification was 79.3%. CONCLUSIONS: CDAS appears to have sufficient face-validity as a grading system to assess disease activity in relation to treatment status. The use of CDAS appears to allow benchmarking of patients with CIDP that may be useful in subject selection for clinical trials and also to highlight differences in practice. PMID- 27653890 TI - Acquired hemophilia A associated with myasthenia gravis and Isaacs' syndrome. PMID- 27653891 TI - Increased likelihood of anxiety and poor sleep quality in Parkinson's disease patients with pain. AB - BACKGROUND: Pain is a bothersome non-motor symptom in patients with Parkinson's disease (PD), but the relationships between PD, presence of pain, different pain characteristics, and other non-motor symptoms such as mood and sleep disturbances are unclear. OBJECTIVE: To investigate the relationship between PD and pain as well as specific subtypes of pain with anxiety, depression and sleep quality. METHODS: This cross-sectional case-control study included two groups of PD patients; one with (n=37) and one without pain (n=37). Healthy controls with (n=37) and without pain (n=37) were recruited and matched to the PD groups for age and gender. All participants completed questionnaires regarding pain, mood and sleep. RESULTS: PD patients with pain showed significantly higher anxiety severity and poorer sleep quality than PD patients without pain. Compared to controls with pain, PD patients with pain had more anxiety, depression and worsened sleep quality. PD patients with pain were more likely to report akathisic, tension and sharp pain compared to controls with pain, but these three pain characteristics did not correlate with each other. There were no differences in depression, anxiety, or sleep between PD patients with akathisic, tension and sharp pain and those without. CONCLUSION: Pain in PD seems to be linked with specific pain characteristics (akathisic, tension and sharp pain) as well as heightened anxiety and worsened sleep quality. Integrative approach treatments which address pain in PD may also improve anxiety and sleep quality. PMID- 27653892 TI - Effect of CYP2C19*2 and *3 on clinical outcome in ischemic stroke patients treated with clopidogrel. AB - BACKGROUND: Despite clopidogrel has been widely applied to patients with ischemic stroke combined with aspirin, decreased metabolic activation of clopidogrel still occurs because of genetic variations in CYP2C19. METHODS: Three hundred twenty one patients completed a genetic test for CYP2C19 loss of function (LOF) alleles in hospital. Cox regression models were used to assess the relationship between CYP2C19 genotypes with the primary endpoint, which was a composite of nonfatal ischemic stroke, myocardial infarction, or vascular death. Functional outcome was measured by the modified Rankin Scale (mRS) at 3months, 6months and 12months intervals. Binary logistic regression was used to analyze the correlation between poor functional outcome and CYP2C19 LOF alleles. RESULTS: The CYP2C19 LOF alleles were independently associated with the primary endpoint. There was no significant association between poor functional outcome and CYP2C19 LOF allele (*2 and *3) in overall patients. After the participants were stratified by stent treatment into two groups, the polymorphisms of CYP2C19 had significant impact on poor prognosis at 3months and 6months but not at 12months in patients without stent. No correlation was found in patients with stent. CONCLUSIONS: The CYP2C19 LOF alleles may increase the recurrent risk of ischemic events. The polymorphisms of CYP2C19 may be predictors of poor functional outcome of patients without stent, and the effect may be weakened by time. PMID- 27653894 TI - Acute reversible seronegative cerebellar ataxia in a young woman with ovarian teratoma. PMID- 27653893 TI - Outcome of antiepileptic drug treatment of 1282 patients with epilepsy, their pharmacovigilance reports and concomitant medication on CNS in an East-Hungarian adult database. AB - OBJECTIVE: The aim of this study was to determine the outcome of antiepileptic drug (AED) treatment based on seizure freedom, pharmacovigilance reports and effects of concomitant medication on the central nervous system (CNS) of adult epileptic patients registered in the East-Hungarian Epilepsy Database. METHODS: Prospective cross-sectional database was compiled from outpatient files between 1992 and 2011. RESULTS: The majority of 1282 treated patients were on monotherapy 894 patients (70%), 286 (22%) on bitherapy and 102 (8%) on polytherapy. Of all treated patients, seizure freedom was achieved by 603 (47%). Among the seizure free patients 464 (77%) were on monotherapy, 115 (19%) on bitherapy and only 24 (4%) on polytherapy. The overall rate of adverse drug reactions (ADRs) was 16.2%. From patients on AED, 279 (22%) took concomitant drugs acting on the CNS. In a logistic regression model, other CNS-related drugs and a number of prescribed antiepileptic drugs had a significant influence on the desired outcome of seizure freedom. On comparing the Proportional Reporting Ratio and 95%CI of older and newer AEDs, no significant superiority of newer AEDs was detected. CONCLUSION: Careful drug selection for epileptic patients must be highlighted in order to improve outcome, reduce ADRs and improve patient compliance. PMID- 27653895 TI - Editor's update and selected articles from the Journal of the Neurological Sciences. PMID- 27653896 TI - Mortality of advanced Parkinson's disease patients treated with deep brain stimulation surgery. AB - OBJECTIVE: Despite the widespread use of deep brain stimulation (DBS) for patients with Parkinson's disease (PD), long-term outcomes remain unclear. We aimed to analyze the mortality of advanced PD patients who received DBS surgery. METHODS: We assessed the survival rate of 158 consecutive advanced PD patients who underwent DBS surgery between April 2002 and May 2014. Kaplan-Meier survival curves were constructed using death as the endpoint. Cox proportional hazards regression models were used to assess the association of clinical risk factors with survival. RESULTS: Twenty-seven (17.1%) PD patients (13 men and 14 women) died during the mean follow-up period of 5.3+/-3.1years. The survival rate was 97% at 3years and 85% at 5years after DBS surgery. Pneumonia (n=7) was the most common specific cause of death. Orthostatic hypotension was more frequent in deceased patients than in survivors (P=0.026). In a step-wise Cox regression analysis, male sex (hazard ratio (HR) = 2.58; 95% confidence interval (CI) = 1.19 5.60; P = 0.016), visual hallucination (HR = 9.53; 95% CI = 3.50-26.01; P < 0.001), and nursing home admission (HR = 6.76; 95% CI = 2.40-18.99; P < 0.001) predicted poor survival. CONCLUSION: The poor survival of advanced PD patients who underwent DBS surgery was associated with male sex, orthostatic hypotension, visual hallucination, and nursing home admission. PMID- 27653897 TI - Association between high biomarker probability of Alzheimer's disease and improvement of clinical outcomes after shunt surgery in patients with idiopathic normal pressure hydrocephalus. AB - We examined the effect of the pathology of Alzheimer's disease (AD) on improvement of clinical symptoms after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). Forty-four iNPH patients were classified into 18 patients with (iNPH/AD+) and 26 patients without (iNPH/AD-) combination with low amyloid beta42 and high total tau in cerebrospinal fluid (CSF). We compared improvements after lumbo-peritoneal shunt surgery (LPS) between the two groups in Timed Up & Go Test, 10-m reciprocating walking test, Digit Symbol Substitution Test, attention test, delayed recall test, Mini-Mental State Examination, iNPH grading scale, Neuropsychiatric Inventory, Zarit Burden Interview, and other evaluations. Three months after LPS, gait, urination, overall cognition, psychomotor speed, attention, and neuropsychiatric symptoms significantly improved in both groups, but the improvement in delayed recall and reduction of caregiver burden were significantly greater in iNPH/AD- than iNPH/AD+. In addition, improvement in delayed recall score after LPS was significantly and negatively correlated with the probability of AD as judged by amyloid beta42 and total tau levels in CSF. Three months after LPS, almost all of the triad symptoms decreased in iNPH patients with and without AD pathology but memory improved only in iNPH patients without AD pathology. PMID- 27653898 TI - Chitinase expression in Alzheimer's disease and non-demented brains regions. AB - BACKGROUND: Alzheimer disease is the most typical form of dementia. The causes of AD are not yet completely understood, but they include a combination of genetic, environmental and lifestyle factors that influence ja person's risk for developing the disease. New biomarkers related to these processes could be important for the diagnosis and follow-up of AD patients. OBJECTIVE: The intent of this study was to weigh the expression levels of chitinases genes in brain regions of late-onset AD (LOAD) patients. MATERIALS AND METHODS: We analysed three microarray datasets obtained from the NCBI in order to verify the expression levels of chitinase genes family in brain biopsies (CR, DLPFC and VC) of LOAD patients compared to healthy subjects. We also divided the sample in function of sex difference and ages. RESULTS: The analysis showed that all chitinases genes were modulated in LOAD brain regions compared to healthy subjects. Furthermore positively correlation was identified between chitinases gene expression and healthy age's subjects. Moreover, it has been shown that CHI3L1 and CHI3L2 were regulated differently in healthy and LOAD brain depending on the sex. CONCLUSION: It is possible to conclude that all chitinases could be considered new potential markers for LOAD disease. PMID- 27653899 TI - Paroxysmal supraventricular tachycardia in anti-musk Myasthenia gravis: A case report. PMID- 27653900 TI - Periodic alternating nystagmus in a patient on long-term lithium medication. PMID- 27653901 TI - A case of non-dystrophic myotonia with concomitant mutations in the SCN4A and CLCN1 genes. AB - Non-dystrophic myotonias are caused by mutations of either the skeletal muscle chloride (CLCN1) or sodium channel (SCN4A) gene. They exhibit several distinct phenotypes, including myotonia congenita, paramyotonia congenita and sodium channel myotonia, and a genotype-phenotype correlation has been established. However, there are atypical cases that do not fit with the standard classification. We report a case of 27-year-old male who had non-dystrophic myotonia with periodic paralysis and two heterozygous mutations, E950K in CLCN1 and F1290L in SCN4A. His mother, who exhibited myotonia without paralytic attack, only harbored E950K, and no mutations were identified in his asymptomatic father. Therefore, the E950K mutation was presumed to be pathogenic, although it was reported as an extremely rare genetic variant. The proband experienced paralytic attacks that lasted for weeks and were less likely to be caused by CLCN1 mutation alone. Functional analysis of the F1290L mutant channel heterologously expressed in cultured cells revealed enhanced activation inducing membrane hyperexcitability. We therefore propose that the two mutations had additive effects on membrane excitability that resulted in more prominent myotonia in the proband. Our case stresses the value of performing genetic analysis of both CLCN1 and SCN4A genes for myotonic patients with an atypical phenotype. PMID- 27653902 TI - RAR-related orphan receptor A (RORA): A new susceptibility gene for multiple sclerosis. AB - Retinoic acid receptor-related orphan receptor alpha (RORA) is proposed to promote Th17 cells differentiation that play a crucial role in many inflammatory diseases, including multiple sclerosis (MS). The gene is also involved in regulation of inflammatory responses and neuronal cell development. The aim of the present study is to determine if any relation exists between RORA rs11639084 and rs4774388 gene polymorphisms on the individual susceptibility of multiple sclerosis. 410 patients with clinically definite MS and 500 ethnically-matched healthy controls participated in this study. Genotyping was performed using tetra primer-amplification refractory mutation system-PCR (4P-ARMS-PCR) method for the mentioned polymorphisms in the RORA gene. Both variants showed significant differences in allele and genotype distributions between the studied groups. Genotypes were risk associated in additive (P-value of 0.0003 and odds ratio equal to 1.7 (95% CI: 1.27-2.26)), dominant (P-value of <0.0001 and odds ratio equal to 0.55 (95% CI: 0.41-0.73)) and recessive (P-value of 0.04 and odds ratio equal to 0.33 (95% CI: (0.12-0.96)) models for rs11639084. However, the rs4774388 genotypes were risk associated in recessive model with a P-value of 0.036 and an odds ratio of 0.62 (95% CI: (0.4-0.97)). To the best of our knowledge this is the first report concerning the association between RORAlpha gene polymorphisms and MS. The further study of RORAlpha related pathways and gene networks might result in the better understanding of the pathophysiology of MS and related symptoms. PMID- 27653903 TI - Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study. AB - Cerebral microbleeds (CMBs) are a potential predictor of future stroke risk with clinical relevance for antithrombotic treatments, especially in ischaemic stroke patients with atrial fibrillation. However, prospective data on CMBs and risk of stroke in this particular stroke population remain scarce. We therefore performed a single centre longitudinal study to investigate CMBs and white matter hyperintensities (WMH) and the risk of future stroke. Consecutive acute stroke patients, admitted during 2008-2012 for presumed cardioembolic stroke due to non valvular atrial fibrillation with available follow-up for the occurrence of recurrent stroke were included in our study. The rate of future stroke between patients with vs. without CMBs and moderate to severe WMH at baseline MRI was compared in separate survival and multivariable Cox regression analyses. A total of 119 cardioembolic stroke patients (49% female, median age: 76; IQR: 68 82years) were included. CMBs were found at baseline in 26/119 (21.8%; 95% CI: 14.8-30.4%) patients. Moderate to severe WMH were present in 27/119 (22.7%; 95% CI: 15.5-31.3%) cases. During a median follow-up time of 17months (IQR: 3 50months), 17 of 119 patients experienced a symptomatic stroke: 14 patients had an ischaemic stoke and 3 had intracerebral haemorrhage. The overall incidence rate for ischaemic stroke and intracerebral haemorrhage was 4.2 (95% CI: 2.3-7.1) and 0.9 (95% CI: 0.5-2.6) per 1000 patient-year of follow-up respectively. In multivariable Cox regression analysis the hazard ratio for total CMB number and the risk of stroke during follow-up was 1.05 (95% CI: 0.99-1.11; p=0.137, per each additional CMB increase), after adjusting for CHAD2S. A similar regression analysis demonstrated that moderate to severe WMHs were independently associated with increased risk of symptomatic stroke at follow-up, after adjusting for CHAD2S (HR: 2.99; 95% CI: 1.01-8.30; p=0.036). Despite the small sample size, our study provides useful data to guide power calculations and likely effect sizes relevant for ongoing and future larger studies and clinical trials. PMID- 27653905 TI - Zika virus associated with sensory polyneuropathy. PMID- 27653904 TI - A case of POEMS mimicking a "Guillain-Barre like" syndrome. PMID- 27653906 TI - An autopsy case of intravascular large B-cell lymphoma with subcortical U-fiber sparing and unique lymphocyte markers. PMID- 27653907 TI - Lumbar disc herniation exacerbating venous hypertension from a spinal perimedullary arteriovenous fistula of the filum terminale. PMID- 27653908 TI - Differences between the behavioral and psychological symptoms of Alzheimer's disease and Parkinson's disease. AB - AIM: We compared the behavioral and psychological symptoms of Alzheimer's disease (AD) and Parkinson's disease (PD) in order to determine the characteristic features of each disorder. METHODS: For this retrospective cohort study, we compared the behavioral and psychological symptoms of 288AD patients and 189 PD patients (mean age, 74.6+/-5.9 and 73.0+/-8.7years respectively). Symptoms were evaluated using the geriatric depression scale (GDS), apathy scale (AS), and Abe's behavioral and psychological symptoms of dementia score (ABS). RESULTS: AD patients had higher AS and ABS scores than PD patients. A gender-dependent comparison showed that ABS scores were worse in female AD patients than in female PD patients (p=0.001). A subscale analysis of ABS scores revealed that male AD patients were only significantly different from male PD patients in 1 item, whereas female AD patients were significantly different from female PD patients in 4 items. Among patients with mild cognitive decline, no differences in affective scores were observed. Alternatively, among patients with moderate cognitive decline, affective scores on all 3 scales were worse in PD patients than in AD patients. CONCLUSIONS: The present age- and gender-matched retrospective analysis identified greater behavioral and psychological disease severity in female AD patients relative to female PD patients, and greater affective severity in PD patients versus AD patients with a similar degree of cognitive decline. PMID- 27653909 TI - Small lymphocytic lymphoma associated with extensive myelopathy: Case report and review of the literature. PMID- 27653910 TI - Bradykinesia in early and advanced Parkinson's disease. AB - BACKGROUND: Motor impairment in Parkinson's disease (PD) includes slowness (bradykinesia), decreased amplitude (hypokinesia), impaired rhythm and a progressive reduction in speed and amplitude during movement repetition (sequence effect). In the present study we aimed to analyse bradykinesia features in newly diagnosed and drug-naive patients with PD. Kinematic data were compared with PD patients in the advanced stages of the disease and with healthy controls. We also investigated the effect of selegiline on motor impairment in early PD. METHODS: Fourteen newly-diagnosed and drug-naive PD patients in the early stage of the disease, 11 patients with advanced PD and 20 healthy controls performed a repetitive finger tapping task. Early PD patients were assessed in two separate sessions at baseline and four weeks after treatment with selegiline (10 mg taken daily). The repetitive finger movement was analysed using kinematic techniques. RESULTS: The speed and amplitude of repetitive finger movement were lower in early PD patients than in healthy controls. Early PD patients also had a progressive decrement of movement amplitude (sequence effect). Patients with advanced PD had lower speed, amplitude and movement regularity during finger tapping in comparison to early PD and healthy controls but no sequence effect. In early PD, selegiline improved both the movement speed and amplitude though it did not influence the sequence effect. CONCLUSIONS: The study yields an objective characterization of motor impairment in early and advanced PD. The kinematic assessment of the effects of selegiline on movement abnormalities in early PD provides a better understanding and interpretation of their pathophysiological mechanisms. PMID- 27653911 TI - New potential-treatment options in brain injury due to acute carbon monoxide poisoning in future. PMID- 27653912 TI - Maintenance immunosuppression in myasthenia gravis. AB - Therapies for myasthenia gravis (MG) include symptomatic and immunosuppressive treatment. Options for immunosuppression include corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, methotrexate, rituximab, cyclophosphamide, intravenous immunoglobulin, plasmapheresis, and thymectomy. The practical aspects of long-term immunosuppressive therapy in MG will be critically reviewed in this article. Treatment for ocular and generalized myasthenia gravis will be discussed. Application of these therapies needs to be considered in conjunction with their efficacy, disease subtypes and severity, and patient co morbidities. PMID- 27653913 TI - Brain glucose metabolism changes in Parkinson's disease patients with CHCHD2 mutation based on (18)F-FDG PET imaging. PMID- 27653914 TI - Effect of the 2013 AHA/ASA guidelines on TPA use in acute ischemic stroke at Assaf Harofeh Medical Center in Israel. AB - BACKGROUND: Use of TPA to treat patients with acute ischemic stroke was introduced in Assaf Harofeh Medical Center (AHMC) in Israel in November 2007 initially with strict adherence to the inclusion/exclusion criteria of the pivotal NINDS TPA studies published in 1995. The treatment window was expanded in 2010 to 4.5h following the results of ECASS-III. Application of the 2013 AHA/ASA Guidelines resulted in further expanded inclusion and relaxed exclusion criteria. DESIGN/METHODS: A retrospective chart review was conducted of patients who received TPA at AHMC to evaluate the additional impact of applying the 2013 guidelines. Number of patients treated, outcomes at discharge, and safety were compared between two periods: May 2011-January 2013 (the 21months preceding the 2013 Guidelines); and February 2013-October 2014 (the 21months after publication of the 2013 Guidelines). Statistical analysis was done using z-tests for differences between proportions, and t-tests to compare means. RESULTS: 63 patients were treated during the immediate pre-2013 Guideline period (36/year, or approximately 5% of patients with ischemic stroke), and 105 during the post-2013 Guidelines period (60/year, approximately 8.3% of patients with ischemic stroke) (p<0.001). During the two periods, respectively: discharges home were 22(34%) and 55(52%) (p<0.05); facility discharges were 29(46%) and 33(31%); and inter hospital transfers were 6(9%), and 11(10% of treated patients). Most transfers were for endovascular treatment. Total treatment-related symptomatic bleeds in the two periods, respectively, was: 4(6%) and 4(4%), and the number of in hospital deaths was 6 (9%) and 6 (6%) (unchanged). CONCLUSIONS: Application of the 2013 AHA/ASA Guidelines resulted in a 64% increase in the number of acute ischemic stroke patients treated with TPA at AHMC with no worsening of aggregate outcomes and no increase in bleeds or deaths. PMID- 27653915 TI - Ranolazine: A potential treatment for refractory neuropathic pain. PMID- 27653916 TI - Factors that impact medical student and house-staff career interest in brain related specialties. AB - PURPOSE: There is a national shortage of physicians in brain related specialties (neurology, neurosurgery and psychiatry), with fewer students training in these specialties. This study explored socio-economic and experiential factors that determined medical trainees' interest in brain related specialties. METHOD: Medical students and house-staff at a state university medical school completed a 46-item questionnaire sent as an anonymous email survey. RESULTS: Survey response rate was 22% (n=258). Eighty-eight (34.1%) trainees were interested in brain related specialties. Prior neuroscience experience (29.6%) and effective medical school neuroscience courses (23.9%) were identified as important by those interested in brain related specialties, while "neurophobia" was reported by 30% of those not interested. Multivariate regression model showed that effective college neuroscience course increased the likelihood for interest in brain related specialties (OR=2.28, 95% CI 1.22, 4.28). Factors which decreased the likelihood included parent's possessing professional degree (OR=0.37, 95% CI 0.17, 0.80), personal annual income>$50,000 (OR=0.40, 0.18, 0.87) and current debt level>=$100,000 (OR=0.33, 0.17, 0.64). The proportion of trainees interested in brain related specialties decreased from 51.7% (1st year medical students) to 27% (4th year students) and 25.3% among house-staff (chi(2) test of trend p=0.001). CONCLUSIONS: Socioeconomic (current personal debt and annual income) and experiential factors (college neuroscience course) influence a medical trainee's interest in brain related specialties. Career guidance and improved, better and early exposure to neurosciences may help mitigate trend for decreased interest in brain related specialties. PMID- 27653917 TI - Identification of novel TFG mutation in HMSN-P pedigree: Emphasis on variable clinical presentations. AB - We aimed to identify the genetic cause of neurological disease in an Iranian pedigree whose manifestations suggested hereditary motor and sensory neuropathy with proximal predominance (HMSN-P). Identification of a p.Gly269Val mutation in TFG, the known HMSN-P causative gene, provided supportive evidence. Subjective, biochemical, electrodiagnostic, and imaging data were compared with previously reported HMSN-P patients, including patients of an earlier described Iranian pedigree. Although notable clinical variability was found, comparable involvement of proximal and distal muscles was observed in both Iranian pedigrees. Interestingly, the same p.Gly269Val mutation was recently reported as cause of Charcot-Marie-Tooth disease type 2 in a Taiwanese pedigree. The likelihood that the two pedigrees with the p.Gly269Val mutation are not affected with different diseases is discussed. Identification of a second Iranian HMSN-P pedigree further confirms that HMSN-P is not confined to the Far East. Furthermore, p.Pro285Leu that has been the only TFG mutation thus far reported in HMSN-P patients is not the only mutation that can cause the disease. It is emphasized HMSN-P is a neuronopathy. PMID- 27653919 TI - Remote preoperative tonic-clonic seizures do not influence outcome after surgery for temporal lobe epilepsy. AB - OBJECTIVES: Tonic-clonic seizures are associated with greater chance of seizure relapse after anterior temporal lobectomy. We investigated whether the interval between the last preoperative tonic-clonic seizure and surgery relates to seizure outcome in patients with drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: In this retrospective study, patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was categorized as seizure freedom or relapse. The relationship between surgical outcome and the interval between the last preoperative tonic-clonic seizure and surgery was investigated. RESULTS: One-hundred seventy-one patients were studied. Seventy nine (46.2%) patients experienced tonic-clonic seizures before surgery. Receiver operating characteristic curve of timing of the last preoperative tonic-clonic seizure was a moderate indicator to anticipate surgery failure (area under the curve: 0.657, significance; 0.016). The best cutoff that maximizes sensitivity and specificity was 27months; with a sensitivity of 0.76 and specificity of 0.60. Cox-Mantel analysis confirmed that the chance of becoming free of seizures after surgery in patients with no or remote history of preoperative tonic-clonic seizures was significantly higher compared with patients with a recent history (i.e., in 27months before surgery) (p=0.0001). CONCLUSIONS: The more remote the occurrence of preoperative tonic-clonic seizures, the better the postsurgical seizure outcome, with at least a two year gap being more favorable. A recent history of tonic-clonic seizures in a patient with MTLE may reflect more widespread epileptogenicity extending beyond the borders of mesial temporal structures. PMID- 27653918 TI - Intracranial atherosclerosis and cerebral small vessel disease in intracerebral hemorrhage patients. AB - BACKGROUND: The association between cerebral small vessel diseases (cSVD) and intracranial atherosclerosis is debated and conflicting results have been reported. We sought to investigate this association in patients with intracerebral hemorrhage (ICH), due to severe cSVD. METHODS: Consecutive ICH patients were divided into those meeting criteria for cerebral amyloid angiopathy (CAA) and those with deep hypertensive ICH consistent with hypertensive cSVD (HTN SVD). White matter hyperintensity volumes (WMH) and microbleed counts (MB) were measured on MRI. CTA was rated for severity of intracranial carotid calcifications and for presence of >50% intracranial stenosis (ICS). Associations of intracranial atherosclerosis severity with type of SVD (CAA vs HTN-cSVD) and with imaging and clinical markers of cSVD burden were analyzed. RESULTS: The cohort included 253 CAA and 90 HTN-SVD patients. In multivariable models, the type of cSVD (CAA vs. HTN-cSVD) was not associated with calcification severity (OR=1.04, 95% CI [0.62-3.5], p=0.37) or presence of ICS (OR=0.84, 95% CI [0.21 2.74], p=0.78). We found no association between intracranial atherosclerosis (calcifications and stenoses) and parenchymal markers of cSVD severity (WMH and MB, adjusted p>=0.2 for all comparisons) and no association with presence of dementia before ICH (adjusted p>=0.2 for both comparisons). CONCLUSIONS: We found no association between intracranial atherosclerosis and parenchymal or clinical consequences of cSVD, suggesting that cSVDs while sharing some risk factors are not influenced by upstream larger vessel pathologies. PMID- 27653920 TI - Osteopathic manipulative treatment in neurological diseases: Systematic review of the literature. AB - OBJECTIVE: The aim of the present systematic review is to critically evaluate the effectiveness of OMT as an adjuvant therapy in the management of patients with neurological diseases. METHODS: A systematic review was conducted and the findings were reported following the PRISMA statement. Twelve databases were searched for articles reporting the use of osteopathic manipulative treatment in neurological disorders. Each article was assessed using the Cochrane risk of bias tool and the Jadad score. RESULTS: 10 articles were included. OMT was used to test its efficacy and/or effectiveness in treating tension-type headache, migraine, cerebral palsy and gait analysis in patients affected by Parkinson's Disease. The general quality of the included trials ranged from very low, to low and moderate according to Cochrane standards. High heterogeneity between studies was found for the type of intervention, control and outcome measures used. CONCLUSION: Results showed that studies on the efficacy and/or effectiveness of OMT treatments are scarce, heterogeneous, and of low methodological quality. Further studies should be conducted including a more pragmatic methodology, an exhaustive description of all investigated and concurrent interventions, and a systematic report of adverse events, so as to obtain robust and generalizable results. PMID- 27653921 TI - Prevalence of anti-SOX1 reactivity in various neurological disorders. AB - OBJECTIVES: Anti-SOX1 antibodies are associated with small cell lung cancer (SCLC) and predict a paraneoplastic etiology in Lambert-Eaton myasthenic syndrome (LEMS). In 2010, a study described these antibodies in a small cohort of putative non-paraneoplastic, immune-mediated neuropathies. In this respect, we investigated the seroprevalence and specificity of anti-SOX1 antibodies in a large cohort of neurological disorders. METHODS: Overall, serum samples of 1493 consecutive patients were screened for anti-SOX1 reactivity by an ELISA: 471 with well-defined neurological disorders (multiple sclerosis, motor neuron disease, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyneuropathy), 185 with polyneuropathy (PNP) of unknown origin, and 837 with neurological syndromes of suspicious paraneoplastic etiology. These were compared to eight positive controls with definite paraneoplastic neurological syndromes (PNS) and 92 healthy individuals. We also collected demographic and clinical data, including well-characterized onconeural antibodies in anti-SOX1-positive patients. RESULTS: Fifteen patients (1.0%) showed anti-SOX1 reactivity: two with multiple sclerosis, two with PNP of unknown origin, and 11 suspicious PNS cases. Remarkably, 9/15 anti-SOX1-positive patients had a PNP. However, antibody concentrations were significantly lower compared to positive controls, and none additionally harbored well-characterized onconeural antibodies. During a follow up of at least four years, only five patients had cancer: one thyroid, one Hodgkin lymphoma, two breast, and one patient had multiple malignancies - prostate, penis, cecum, liver, and non-small cell lung cancer. However, none had SCLC, typically associated with SOX1 antibodies. CONCLUSIONS: The seroprevalence of anti-SOX1 antibodies in patients with various neurological disorders is low. These patients predominantly have PNPs, which might represent a group of immune mediated diseases. PMID- 27653923 TI - When the word doesn't come out: A synthetic overview of dysarthria. AB - Motor speech disorders are common in a number of neurological conditions including diseases involving impairment of the pyramidal, extrapyramidal, and cerebellar pathways, cranial nerves, muscular apparatus, neuromuscular plaque, and of cognitive, symbolic and mnestic activities. The diagnosis of speech disorders, namely the dysarthrias, involves the assessment of characteristic structural cerebral, prosodic, phonetic and phonemic changes, often flanked by concomitant functional, clinical, neuroradiological, neurophysiological and behavioral impairment. This paper presents a brief outline of the most significant associations to facilitate prompt differential diagnosis and thereby reduce the number of instrumental examinations required for diagnostic testing. PMID- 27653922 TI - Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease. AB - OBJECTIVE: The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias. METHODS: Cognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions. RESULTS: The COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women. CONCLUSIONS: Our results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication. PMID- 27653925 TI - Reliability of the functional measures of the corticospinal pathways to dorsiflexor muscles during maximal voluntary contractions. AB - This study aimed to evaluate the intra- and inter-day reliability of transcranial magnetic stimulation (TMS)-related measurements recorded from the tibialis anterior (TA) muscle. Thirteen healthy young men and women (23+/-4years) performed 3 testing sessions to assess intra- (i.e., two sessions performed the same day) and inter-day (i.e. two sessions performed one week apart) reliability of (i) dorsiflexion cortical maximal voluntary activation level (VATMS), (ii) TA corticospinal excitability assessed through the amplitude of the motor evoked potentials (MEP) recorded during 100, 75 and 50% maximal voluntary contractions (MVC), and (iii) intracortical inhibition investigated via the cortical silent period (CSP) recorded at the same % MVC. Absolute (i.e., coefficient of variation (CV) and standard error of the mean (SEM)), and relative (i.e., intraclass correlation coefficients (ICC)) reliability parameters were calculated. VATMS demonstrated excellent intra- and inter-day reliabilities (ICC: 0.80 and 0.99; CV: 1.7 and 0.8%, respectively). MEPs and CSPs presented moderate to excellent intra- and inter-day reliabilities, while input-output curves extracted parameters presented highly variable outcomes. These results suggest that most TA corticospinal measurements during voluntary contractions can be used to quantify corticospinal adaptations after acute (e.g. fatigue) or long term (e.g. training) interventions. PMID- 27653924 TI - Neuroprotective effects of methane-rich saline on experimental acute carbon monoxide toxicity. AB - BACKGROUND: Methane has been reported to play a protective role in ischemia reperfusion injury via anti-oxidation, anti-inflammatory and anti-apoptotic activities. This study was designed to determine the protective effects of methane-rich saline (MRS) on acute carbon monoxide (CO) poisoning. METHODS: A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups: sham group, CO group and MRS group. Acute CO poisoning was induced by exposing rats to 1000ppm CO in air for 40min and then to 3000ppm CO for an additional 20min until they lost consciousness. MRS at 10ml/kg was intraperitoneally administered at 0h, 8h and 16h after CO exposure. Rats were sacrificed 24h after CO exposure. Brains were collected for Nissl staining. The cortex and hippocampus were separated for the detections of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8 hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-alpha), interleukin1-beta (IL-1beta), interleukin-6 (IL-6) and superoxide dismutase (SOD) activities. RESULTS: The results showed that MRS treatment improved neuronal injury, reduced MDA, 3-NT and 8-OHdG, and increased SOD activity of the hippocampus and cortex compared with normal saline-treated rats. In addition, MRS reduced the expression of TNF-alpha and IL-1beta in the brain but had no effect on IL-6 expression. CONCLUSION: These findings suggest that MRS may protect the brain against acute CO poisoning-induced injury via its anti-oxidative and anti inflammatory activities. PMID- 27653926 TI - Superior binasal quadrantanopsia due to acute ischemic stroke. PMID- 27653928 TI - Sensitive Determination of Sertraline in Commercial Drugs and Its Stability Check in Simulated Gastric Juice. AB - A sensitive analytical method was developed for the determination of sertraline in commercial drug samples by using GC-MS. The selected-ion monitoring mode was used at the most sensitive m/z 274 to obtain a lower detection limit. LOD/LOQ values were obtained as 1.6/5.4 ng/mL for sertraline under the optimum conditions. The calibration plot was linear between 5.0 and 2000 ng/mL with the correlation coefficient of 0.9999. The validated method was successfully applied to three different brands of drug samples for both qualitative and quantitative measurement of sertraline. In this experiment, four replicate extractions were performed for each brand, and the results were compared to the values written on the labels of the drug brands. Spiking experiments were also performed to check the effect of the matrixes on the determination, and it was observed that there was no shift in the retention time of the analyte. In addition, simulated gastric juice experiments were performed to check the stability of sertraline in the stomach for 240 min, and it was observed that there was no change in the structure of the analyte. PMID- 27653927 TI - Inflammatory myopathies and lymphoma. AB - The inflammatory myopathies comprise a group of immune-mediated muscle diseases. Lymphoma is a term for a variety of lymphatic system malignancies. Autoimmune diseases and lymphoproliferative malignancies share a complex bidirectional relationship. A causal relationship between inflammatory mypathies and lymphoma has not been established. The diagnosis/treatment of inflammatory myopathy usually precedes the detection/diagnosis of lymphoma. Immune system dysregulation presumably underlies the evolution of lymphoma in patients with inflammatory myopathies. Inflammatory activity with chronic B-cell activation and/or antigen stimulation is deemed the major risk factor for lymphoma in patients with autoimmunity. A "paraneoplastic" phenomenon or the effects of immunosuppressive therapy may be alternative immune-based mechanisms. In chronic lymphocytic leukemia immune system disturbance rarely results in non-hematological autoimmune disease, including inflammatory myopathies. PMID- 27653929 TI - Mesoscale Polymer Dissolution Probed by Raman Spectroscopy and Molecular Simulations. AB - The diffusion of various solvents into a polystyrene (PS) matrix was probed experimentally by monitoring the temporal profiles of the Raman spectra and theoretically from molecular dynamics simulations. The simulation results assist in providing a fundamental, molecular-level connection between the mixing/dissolution processes and the difference, Deltadelta = deltasolvent - deltaPS, in the values of the Hildebrand parameter (delta) between the two components of the binary systems: solvents having values of delta similar to those for PS (small Deltadelta) exhibit fast diffusion into the polymer matrix, whereas the diffusion slows down considerably when the delta's are different (large Deltadelta). To this end, the Hildebrand parameter was identified as a useful descriptor that governs the process of mixing in polymer-solvent binary systems. The experiments also provide insight into further refinements of the models specific to non-Fickian diffusion phenomena that need to be used in the simulations. PMID- 27653930 TI - Lysosome-Targeted Turn-On Fluorescent Probe for Endogenous Formaldehyde in Living Cells. AB - As one of the simplest reactive carbonyl species, formaldehyde is implicated in nervous system diseases and cancer. Organelles play crucial roles in various physiological processes in living cells. Accordingly, the detection of endogenous formaldehyde at the subcellular level is of high interest. We herein describe the development of the first organelle-targeted fluorescent formaldehyde probe (Na-FA Lyso). The new probe exhibits favorable features including a large fluorescence enhancement (about 350-fold) and a fast response to formaldehyde. Significantly, the novel probe Na-FA-Lyso was employed to visualize the endogenous formaldehyde in the lysosomes in living cells for the first time. PMID- 27653931 TI - Quantifying tissue viscoelasticity using optical coherence elastography and the Rayleigh wave model. AB - This study demonstrates the feasibility of using the Rayleigh wave model (RWM) in combination with optical coherence elastography (OCE) technique to assess the viscoelasticity of soft tissues. Dispersion curves calculated from the spectral decomposition of OCE-measured air-pulse induced elastic waves were used to quantify the viscoelasticity of samples using the RWM. Validation studies were first conducted on 10% gelatin phantoms with different concentrations of oil. The results showed that the oil increased the viscosity of the gelatin phantom samples. This method was then used to quantify the viscoelasticity of chicken liver. The Young's modulus of the chicken liver tissues was estimated as E=2.04+/ 0.88??kPa with a shear viscosity ?=1.20+/-0.13??Pa?s. The analytical solution of the RWM correlated very well with the OCE-measured phased velocities (R2=0.96+/ 0.04). The results show that the combination of the RWM and OCE is a promising method for noninvasively quantifying the biomechanical properties of soft tissues and may be a useful tool for detecting disease. PMID- 27653932 TI - Profiling of individual human red blood cells under osmotic stress using defocusing microscopy. AB - We use a quantitative phase imaging technique, defocusing microscopy (DM), to measure morphological, chemical, and mechanical parameters of individual red blood cells (RBCs) immersed in solutions with different osmolalities. We monitor the RBCs' radius, volume, surface area, sphericity index, and hemoglobin content and concentration. The complete shape of cells is recovered and the effects of their adhesion to the glass substrate are observed. Finally, membrane fluctuation measurements give us information about the cells deformability. PMID- 27653933 TI - Effect of the antimicrobial photodynamic therapy on microorganism reduction in deep caries lesions: a systematic review and meta-analysis. AB - This study aimed to perform a systematic review to assess the effectiveness of antimicrobial photodynamic therapy (aPDT) in the reduction of microorganisms in deep carious lesions. An electronic search was conducted in Pubmed, Web of Science, Scopus, Lilacs, and Cochrane Library, followed by a manual search. The MeSH terms, MeSH synonyms, related terms, and free terms were used in the search. As eligibility criteria, only clinical studies were included. Initially, 227 articles were identified in the electronic search, and 152 studies remained after analysis and exclusion of the duplicated studies; 6 remained after application of the eligibility criteria; and 3 additional studies were found in the manual search. After access to the full articles, three were excluded, leaving six for evaluation by the criteria of the Cochrane Collaboration's tool for assessing risk of bias. Of these, five had some risk of punctuated bias. All results from the selected studies showed a significant reduction of microorganisms in deep carious lesions for both primary and permanent teeth. The meta-analysis demonstrated a significant reduction in microorganism counts in all analyses (p<0.00001). Based on these findings, there is scientific evidence emphasizing the effectiveness of aPDT in reducing microorganisms in deep carious lesions. PMID- 27653934 TI - Estimation of optical properties by spatially resolved reflectance spectroscopy in the subdiffusive regime. AB - We propose and objectively evaluate an inverse Monte Carlo model for estimation of absorption and reduced scattering coefficients and similarity parameter ? from spatially resolved reflectance (SRR) profiles in the subdiffusive regime. The similarity parameter ? carries additional information on the phase function that governs the angular properties of scattering in turbid media. The SRR profiles at five source-detector separations were acquired with an optical fiber probe. The inverse Monte Carlo model was based on a cost function that enabled robust estimation of optical properties from a few SRR measurements without a priori knowledge about spectral dependencies of the optical properties. Validation of the inverse Monte Carlo model was performed on synthetic datasets and measured SRR profiles of turbid phantoms comprising molecular dye and polystyrene microspheres. We observed that the additional similarity parameter ? substantially reduced the reflectance variability arising from the phase function properties and significantly improved the accuracy of the inverse Monte Carlo model. However, the observed improvement of the extended inverse Monte Carlo model was limited to reduced scattering coefficients exceeding ?15??cm?1, where the relative root-mean-square errors of the estimated optical properties were well within 10%. PMID- 27653935 TI - Image recombination transform algorithm for superresolution structured illumination microscopy. AB - Structured illumination microscopy (SIM) is an attractive choice for fast superresolution imaging. The generation of structured illumination patterns made by interference of laser beams is broadly employed to obtain high modulation depth of patterns, while the polarizations of the laser beams must be elaborately controlled to guarantee the high contrast of interference intensity, which brings a more complex configuration for the polarization control. The emerging pattern projection strategy is much more compact, but the modulation depth of patterns is deteriorated by the optical transfer function of the optical system, especially in high spatial frequency near the diffraction limit. Therefore, the traditional superresolution reconstruction algorithm for interference-based SIM will suffer from many artifacts in the case of projection-based SIM that possesses a low modulation depth. Here, we propose an alternative reconstruction algorithm based on image recombination transform, which provides an alternative solution to address this problem even in a weak modulation depth. We demonstrated the effectiveness of this algorithm in the multicolor superresolution imaging of bovine pulmonary arterial endothelial cells in our developed projection-based SIM system, which applies a computer controlled digital micromirror device for fast fringe generation and multicolor light-emitting diodes for illumination. The merit of the system incorporated with the proposed algorithm allows for a low excitation intensity fluorescence imaging even less than 1??W/cm2, which is beneficial for the long-term, in vivo superresolved imaging of live cells and tissues. PMID- 27653936 TI - In vivo optical coherence tomography of stimulus-evoked intrinsic optical signals in mouse retinas. AB - Intrinsic optical signal (IOS) imaging promises a noninvasive method for advanced study and diagnosis of eye diseases. Before pursuing clinical applications, it is essential to understand anatomic and physiological sources of retinal IOSs and to establish the relationship between IOS distortions and eye diseases. The purpose of this study was designed to demonstrate the feasibility of 0.5 International Units (IU)/mL was chosen as the threshold of seroconversion. Participants with titers <=0.5 IU/mL or Equivalent Units (EU)/mL at enrollment or at subsequent annual visits received booster doses of purified Vero cell rabies vaccine (PVRV). Adherence of the participants from this Amazonian community to the study protocol was excellent, with 428 of the 509 (84%) who attended the first interview in 2007 returning for the final visit in 2009. The long-term RVNA persistence was good, with 85-88.0% of the non-boosted participants evaluated at each yearly follow-up visit remaining seroconverted. Similar RVNA persistence profiles were observed in participants originally given PEP or PrEP in 2005, and the GMT of the study population remained >1 IU/mL 4 years after vaccination. At the end of the study, 51 subjects (11.9% of the interviewed population) had received at least one dose of booster since their vaccination in 2005. CONCLUSIONS/SIGNIFICANCE: This study and the events preceding it underscore the need for the health authorities in rabies enzootic countries to decide on the best strategies and timing for the introduction of routine rabies PrEP vaccination in affected areas. PMID- 27653950 TI - Mindfulness and dermatology. PMID- 27653949 TI - Lay knowledge and management of malaria in Baringo county, Kenya. AB - BACKGROUND: Malaria, a disease caused by protozoan parasites of the genus Plasmodium and transmitted by female anopheline mosquitoes, is a major cause of morbidity, mortality and loss in productivity in humans. Baringo County is prone to seasonal transmissions of malaria mostly in the rainy seasons. METHODS: This cross-sectional study used a mixed methods approach to collect data on knowledge and lay management of malaria. A questionnaire survey was administered to 560 respondents while qualitative data was collected through 20 focus group discussions in four ecological zones covering Baringo North, Baringo South and Marigat sub-Counties of Baringo County. Analyses were done through summary and inferential statistics for quantitative data and content analysis for qualitative data. RESULTS: The study communities were knowledgeable of malaria signs, symptoms, cause and seasonality but this biomedical knowledge co-existed with other local perceptions. This knowledge, however, did not influence their first (p = 0.77) or second choice treatments (p = 0.49) and compliance to medication (p = 0.84). Up to 88 % of respondents reported having suffered from malaria. At the onset of a suspected malaria case community members reported the following: 28.9 % visited a health facility, 37.2 % used analgesics, 26.6 % herbal treatments, 2.2 % remnant malaria medicines, 2.2 % over the counter malaria medicines, 1 % traditional healers and 1.8 % other treatments. Nearly all respondents (97.8 %) reported visiting a health facility for subsequent treatments. Herbal treatments comprised of infusions and decoctions derived from roots, barks and leaves of plants believed to have medicinal value. Compliance to conventional malaria treatment regime was, however, identified as a challenge in malaria management. Quick relief from symptoms, undesirable qualities like drug bitterness and bad smell, undesirable side-effects, such as nausea and long regimen of treatment were some of the contributors to non-compliance. Men and women exhibited different health-seeking behaviours based on the cultural expectations of masculinity, femininity, gender roles and acceptability of health services. CONCLUSIONS: While knowledge of malaria is important in identifying the disease, it does not necessarily lead to good management practice. Treatment-seeking behaviour is also influenced by perceived cause, severity of disease, timing, anticipated cost of seeking treatment and gender, besides the availability of both traditional and conventional medicines. PMID- 27653951 TI - One-Component Dual Actuation: Poly(NIPAM) Can Actuate to Stable 3D Forms with Reversible Size Change. AB - A rare example of a one-component dual actuator is provided, which displays irreversible change in shape by rolling on contact with water and reversible size change on changing the temperature. The actuator has a bilayer structure with aligned and randomly oriented fibers of poly(N-isopropyl acrylamide). A combination of anisotropic E modulus and temperature dependent swelling/shrinkage provides the dual actuation. PMID- 27653952 TI - European Society of Cardiology 2016 Congress. PMID- 27653953 TI - Juxtapapillary Duodenal Diverticulum Impacted with Enterolith. AB - A 64-year-old man underwent abdominal computed tomography (CT) as periodic follow up following a distal gastrectomy with lymphadenectomy for gastric cancer and mucosal-associated lymphoid tissue (MALT) lymphoma conducted 31 months earlier. Contrast-enhanced CT demonstrated a well-circumscribed mass lesion with heterogeneous density measuring 2.2 cm in diameter located between the second segment of the duodenum and uncinate process of the pancreas. Esophagogastroduodenoscopy revealed no remarkable findings in the remnant stomach; however, the scope could not reach the duodenum due to altered anatomy by Roux-en-Y reconstruction after the distal gastrectomy. The patient underwent surgical resection of the mass lesion under the clinical diagnosis of MALT lymphoma relapse. An orange calculus was apparent in the thinly extended duodenal wall on stretching, and the hall was closed by meticulous primary suture after the duodenal resection. Macroscopically, the extracted calculus was solid and quite hard, measured 2.2 * 2.1 * 2.1 cm, and the cut surface revealed a layered structure in the outer areas with granulated contents in the center. Although duodenal diverticula are relatively common, an enterolith developing within a juxtapapillary duodenal diverticulum is rare, and to the best of our knowledge, this is the first such case due to altered anatomy after gastrectomy reported in the English literature. PMID- 27653954 TI - Xanthogranulomatous Cholecystitis. PMID- 27653955 TI - A New Scale for Assessing the Severity of Uncomplicated Diaper Dermatitis in Infants: Development and Validation. AB - BACKGROUND: One methodologic challenge in conducting research relating to diaper dermatitis (DD) is the absence of a reliable, objective, validated scale for assessing severity. The aim of this study was to develop and validate such a scale. METHODS: Scale development was based on experience of DD assessment and clinical and photographic data collected during the early stages of a randomized controlled trial of two DD treatments. The severity score is the sum of scores of four domains: severity of erythema and irritation, area with any DD, papules or pustules, and open skin. Possible scores range from 0 (clear skin) to 6 (extensive DD including intense erythema, papules or pustules, and open skin with damage to the dermis). Assessors used the scale to attribute severity scores using high-definition photographs of infants and babies with DD. Interrater reliability (IRR), internal consistency, and test-retest reliability were considered using intraclass correlation coefficients (ICCs), Cronbach's alpha, and Cohen kappa statistics. RESULTS: IRR was very good between assessors familiar with the scale (ICC = 0.949, p < 0.001) and between assessors unfamiliar with the scale (ICC = 0.850, p < 0.001). Test-retest reliability at 2 weeks was good (kappa = 0.603, p < 0.001). Cronbach's alpha for internal consistency was 0.702. Collation of photographs according to severity score revealed a visible continuum of DD severity, suggesting good construct validity. CONCLUSION: The newly developed scale appears to be easy to use, reliable, and effective in detecting increasing or lessening DD severity. PMID- 27653957 TI - Ultra-Fast Degradation of Chemical Warfare Agents Using MOF-Nanofiber Kebabs. AB - The threat associated with chemical warfare agents (CWAs) motivates the development of new materials to provide enhanced protection with a reduced burden. Metal-organic frame-works (MOFs) have recently been shown as highly effective catalysts for detoxifying CWAs, but challenges still remain for integrating MOFs into functional filter media and/or protective garments. Herein, we report a series of MOF-nanofiber kebab structures for fast degradation of CWAs. We found TiO2 coatings deposited via atomic layer deposition (ALD) onto polyamide-6 nanofibers enable the formation of conformal Zr-based MOF thin films including UiO-66, UiO-66-NH2 , and UiO-67. Cross-sectional TEM images show that these MOF crystals nucleate and grow directly on and around the nanofibers, with strong attachment to the substrates. These MOF-functionalized nanofibers exhibit excellent reactivity for detoxifying CWAs. The half-lives of a CWA simulant compound and nerve agent soman (GD) are as short as 7.3 min and 2.3 min, respectively. These results therefore provide the earliest report of MOF nanofiber textile composites capable of ultra-fast degradation of CWAs. PMID- 27653956 TI - Durum wheat seedling responses to simultaneous high light and salinity involve a fine reconfiguration of amino acids and carbohydrate metabolism. AB - Durum wheat plants are extremely sensitive to drought and salinity during seedling and early development stages. Their responses to stresses have been extensively studied to provide new metabolic targets and improving the tolerance to adverse environments. Most of these studies have been performed in growth chambers under low light [300-350 umol m-2 s-1 photosynthetically active radiation (PAR), LL]. However, in nature plants have to face frequent fluctuations of light intensities that often exceed their photosynthetic capacity (900-2000 umol m-2 s-1 ). In this study we investigated the physiological and metabolic changes potentially involved in osmotic adjustment and antioxidant defense in durum wheat seedlings under high light (HL) and salinity. The combined application of the two stresses decreased the water potential and stomatal conductance without reducing the photosynthetic efficiency of the plants. Glycine betaine (GB) synthesis was inhibited, proline and glutamate content decreased, while gamma-aminobutyric acid (GABA), amides and minor amino acids increased. The expression level and enzymatic activities of Delta1-pyrroline-5-carboxylate synthetase, asparagine synthetase and glutamate decarboxylase, as well as other enzymatic activities of nitrogen and carbon metabolism, were analyzed. Antioxidant enzymes and metabolites were also considered. The results showed that the complex interplay seen in durum wheat plants under salinity at LL was simplified: GB and antioxidants did not play a main role. On the contrary, the fine tuning of few specific primary metabolites (GABA, amides, minor amino acids and hexoses) remodeled metabolism and defense processes, playing a key role in the response to simultaneous stresses. PMID- 27653958 TI - Predicting the functional motions of p97 using symmetric normal modes. AB - p97 is a protein complex of the AAA+ family. Although functions of p97 are well understood, the mechanism by which p97 performs its unfolding activities remains unclear. In this work, we present a novel way of applying normal mode analysis to study this six-fold symmetric molecular machine. By selecting normal modes that are axial symmetric and give the largest movements at D1 or D2 pore residues, we are able to predict the functional motions of p97, which are then validated by experimentally observed conformational changes. Our results shed light and provide new understandings on several key steps of the p97 functional process that were previously unclear or controversial, and thus are able to reconcile multiple previous findings. Specifically, our results reveal that (i) a venous valve-like mechanism is used at D2 pore to ensure a one-way exit-only traffic of substrates; (ii) D1 pore remains shut during the functional process; (iii) the "swing-up" motion of the N domain is closely coupled with the vertical motion of the D1 pore along the pore axis; (iv) because of the shut D1 pore and the one-way traffic at D2 pore, it is highly likely that substrates enter the chamber through the gaps at the D1/D2 interface. The limited chamber volume inside p97 suggests that a substrate may be pulling out from D2 while at the same time being pulling in at the interface; (v) lastly, p97 uses a series of actions that alternate between twisting and pulling to remove the substrate. Proteins 2016; 84:1823 1835. (c) 2016 Wiley Periodicals, Inc. PMID- 27653959 TI - Higher prevalence of wheezing and lower FEV1 and FVC percent predicted in adults with sickle cell anaemia: A cross-sectional study. AB - BACKGROUND AND OBJECTIVE: Respiratory symptoms including wheezing are common in adults with sickle cell anaemia (SCA), even in the absence of asthma. However, the prevalence of spirometry changes and respiratory symptoms in adults with SCA is unknown. METHODS: Using a cross-sectional study design, we tested the hypothesis that adults with SCA (cases) would have higher rates of lower airway obstruction and wheezing than those without SCA (controls) using the American Thoracic Society Division of Lung Diseases' questionnaire. Patients were adults with SCA aged between 18 and 65 years. Controls were consecutive unselected individuals without SCA who presented to an outpatient general medicine clinic. RESULTS: We enrolled 150 adults with SCA and 287 consecutive controls without SCA. The median age was 23.0 and 27.0 years for adults with and without SCA, respectively. Cases were more likely to report cough without a cold (35.0% vs 18.6%, P < 0.001), lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.1% vs 82.1%, P = 0.001) and lower forced vital capacity (FVC) % predicted (67.4% vs 74.9%, P = 0.001) than controls. In the multivariable model, wheezing was significantly associated with SCA status (OR = 1.69, 95% CI = 1.08-2.65, P = 0.024). Similarly, FEV1 % predicted was significantly associated with SCA status and wheezing (P = 0.001 for both). CONCLUSION: Adults with SCA experience a higher rate of wheezing and impaired respiratory functions compared with controls from the same region. PMID- 27653960 TI - Systematic literature review on effectiveness of self-management support interventions in patients with chronic conditions and low socio-economic status. AB - AIM: To assess the quality of evidence and determine the effect of patient related and economic outcomes of self-management support interventions in chronically ill patients with a low socio-economic status. BACKGROUND: Integrated evidence on self-management support interventions in chronically ill people with low socio-economic status is lacking. DESIGN: Systematic literature review. DATA SOURCES: Cochrane database of trials, PubMed, CINAHL, Web of Science, PsycINFO and Joanna Briggs Institute Library were searched (2000-2013). Randomized controlled trials addressing self-management support interventions for patients with cardiovascular disease, stroke, cancer, diabetes and/or chronic respiratory disease were included. REVIEW METHODS: Data extraction and quality assessment were performed by independent researchers using a data extraction form. RESULTS: Studies (n = 27) focused mainly on diabetes. Fourteen studies cited an underlying theoretical basis. Most frequently used self-management support components were lifestyle advice, information provision and symptom management. Problem-solving and goal-setting strategies were frequently integrated. Eleven studies adapted interventions to the needs of patients with a low socio-economic status. No differences were found for interventions developed based on health behaviour theoretical models. CONCLUSION: Limited evidence was found for self-management support interventions in chronically ill patients with low socio-economic status. Essential characteristics and component(s) of effective self-management support interventions for these patients could not be detected. Rigorous reporting on development and underlying theories in the intervention is recommended. PMID- 27653962 TI - Atherogenic high cholesterol/high fat diet induces TLRs-associated pulmonary inflammation in C57BL/6J mice. AB - OBJECTIVE: To explore the effects of high cholesterol/high fat diet-induced hypercholesterolemia on pulmonary homeostasis of wild-type C57BL/6J mice. MATERIALS AND METHODS: Six- to eight-week-old male C57BL/6J mice were randomly divided into two groups and treated with either high cholesterol/high fat diet (HCD, containing 20 % fat, 1.25 % cholesterol and 0.5 % sodium cholate) or a matching regular diet (RD, containing 4 % fat with no cholesterol and cholate added) for 12-16 weeks. RESULTS: Twelve to sixteen weeks after HCD diet feeding, hypercholesterolemia and pulmonary lipid accumulation were progressively exacerbated in C57BL/6J mice. Meanwhile, the HCD-fed mice showed distinctive signs of inflammation in the lung, which includes macrophage accumulation in alveolar lumen and lymphocyte infiltration around perivascular area. Simultaneously, the mRNA and protein expression of TLR2 and TLR4 were significantly up-regulated, and the translocation of NFkappaB into nucleus was activated in HCD-fed mice lung. In vitro, oxidized low-density lipoprotein (oxLDL) could directly up-regulate the expression of TLR2 and TLR4 in both A549 and MLE-12 lung epithelial cell lines. CONCLUSIONS: These findings suggested that high cholesterol/high fat diet-induced hypercholesterolemia could result in TLRs/NFkappaB pathway-associated low-grade pulmonary inflammation in C57BL/6J mice, which might alter the lung's immune responsiveness to a variety of environmental exposures. PMID- 27653963 TI - Differential Characteristics of Kidney Transplant Recipients According to 1-Year Chronic Kidney Disease Stage 3a and Stage 3b Graft Function. AB - The outcomes of transplantation have improved, but more than 50% of kidney transplantation (KT) recipients are still reported to have renal function of chronic kidney disease (CKD) stage 3 at 1 year after KT. We reviewed all 1235 patients who received a KT in our institution between 2008 and 2012. Among these recipients, 77 and 289 cases were included in the estimated glomerular filtration rate (eGFR) at 1 year after KT 30-44 (CKD stage 3b) group and eGFR 45-59 (CKD stage 3a) group, respectively. Longer duration of dialysis (odds ratio [OR] = 1.007, 95% confidence interval [CI], 1.000-1.014, P = 0.047), older donors (OR = 1.064, 95% CI, 1.031-1.098, P < 0.001), delayed graft function (OR = 3.601, 95% CI, 1.031-1.098, P < 0.001), BK virus infection (OR = 2.567, 95% CI, 1.242-5.305, P = 0.011), and pneumonia (OR = 4.451, 95% CI, 1.388-14.279, P = 0.012) were contributing factors to eGFR 30-44 mL/min. Especially, ureteral stricture occurred more frequently in eGFR 30-44 group of deceased donor KT. However, acute rejection was not a significant risk factor of lower eGFR. Graft survival was better in the eGFR 45-59 group. However, this difference was smaller in deceased donor KT. Infections and urologic complications are also important contributing factors of lower graft function in CKD stage 3. In addition, dividing CKD stage 3 into subgroups might be more useful in living donor kidney transplantation. PMID- 27653964 TI - The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns. AB - There is a widespread exposure of general population, including pregnant women and developing fetuses, to the endocrine disrupting chemicals (EDCs). These chemicals have been reported to be present in urine, blood serum, breast milk, and amniotic fluid. Endocrine disruptions induced by environmental toxicants have placed a heavy burden on society, since environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life-a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical, and cellular events. Humans may encounter EDCs daily and during all stages of life, from conception and fetal development through adulthood and senescence. Nevertheless, prenatal and early postnatal windows are the most critical for proper development, due to rapid changes in system growth. Although there are still gaps in our knowledge, currently available data support the urgent need for health and environmental policies aimed at protecting the public and, in particular, the developing fetus and women of reproductive age. Birth Defects Research (Part C) 108:224-242, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27653961 TI - Prolonged inflammatory microenvironment is crucial for pro-neoplastic growth and genome instability: a detailed review. AB - INTRODUCTION: Chronic inflammation can affect the normal cell homeostasis and metabolism by rendering the cells susceptible to genomic instability that may lead to uncontrolled cellular growth and proliferation ensuing tumorigenesis. The causal agents for inflammation may be pathogenic infections like microbial agents ranging from viruses to bacteria. These infections lead to DNA damage or disruption of normal cell metabolism and alter the genome integrity. FINDINGS: In this review, we have highlighted the role of recurrent infections in tumor microenvironment can lead to recruitment of pro-inflammatory cells, cytokines and growth factors to the site of inflammation. This makes the environment rich in cytokines, chemokines, DNA-damaging agents (ROS, RNS) and growth factors which activate DNA damage response pathway and help in sustained proliferation of the tumor cells. In any inflammatory response, the production of cytokines and related signaling molecules is self-regulating and limiting. But in case of neoplastic risk, deregulation of these factors may lead to abnormalities and related pathogenesis. CONCLUSION: The scope of the present review is to explore the probable mechanistic link and factors responsible for chronic inflammation. The relation between chronic inflammation and DNA damage response was further elucidated to understand the mechanism by which it makes the cells susceptible to carcinogenesis. PMID- 27653965 TI - The impact of rate heterogeneity on inference of phylogenetic models of trait evolution. AB - Rates of trait evolution are known to vary across phylogenies; however, standard evolutionary models assume a homogeneous process of trait change. These simple methods are widely applied in small-scale phylogenetic studies, whereas models of rate heterogeneity are not, so the prevalence and patterns of potential rate variation in groups up to hundreds of species remain unclear. The extent to which trait evolution is modelled accurately on a given phylogeny is also largely unknown because studies typically lack absolute model fit tests. We investigated these issues by applying both rate-static and variable-rates methods on (i) body mass data for 88 avian clades of 10-318 species, and (ii) data simulated under a range of rate-heterogeneity scenarios. Our results show that rate heterogeneity is present across small-scaled avian clades, and consequently applying only standard single-process models prompts inaccurate inferences about the generating evolutionary process. Specifically, these approaches underestimate rate variation, and systematically mislabel temporal trends in trait evolution. Conversely, variable-rates approaches have superior relative fit (they are the best model) and absolute fit (they describe the data well). We show that rate changes such as single internal branch variations, rate decreases and early bursts are hard to detect, even by variable-rates models. We also use recently developed absolute adequacy tests to highlight misleading conclusions based on relative fit alone (e.g. a consistent preference for constrained evolution when isolated terminal branch rate increases are present). This work highlights the potential for robust inferences about trait evolution when fitting flexible models in conjunction with tests for absolute model fit. PMID- 27653966 TI - Actigraphy features for predicting mobility disability in older adults. AB - Actigraphy has attracted much attention for assessing physical activity in the past decade. Many algorithms have been developed to automate the analysis process, but none has targeted a general model to discover related features for detecting or predicting mobility function, or more specifically, mobility impairment and major mobility disability (MMD). Men (N = 357) and women (N = 778) aged 70-89 years wore a tri-axial accelerometer (Actigraph GT3X) on the right hip during free-living conditions for 8.4 +/- 3.0 d. One-second epoch data were summarized into 67 features. Several machine learning techniques were used to select features from the free-living condition to predict mobility impairment, defined as 400 m walking speed <0.80 m s-1. Selected features were also included in a model to predict the first occurrence of MMD-defined as the loss in the ability to walk 400 m. Each method yielded a similar estimate of 400 m walking speed with a root mean square error of ~0.07 m s-1 and an R-squared values ranging from 0.37-0.41. Sensitivity and specificity of identifying slow walkers was approximately 70% and 80% for all methods, respectively. The top five features, which were related to movement pace and amount (activity counts and steps), length in activity engagement (bout length), accumulation patterns of activity, and movement variability significantly improved the prediction of MMD beyond that found with common covariates (age, diseases, anthropometry, etc). This study identified a subset of actigraphy features collected in free-living conditions that are moderately accurate in identifying persons with clinically assessed mobility impaired and significantly improve the prediction of MMD. These findings suggest that the combination of features as opposed to a specific feature is important to consider when choosing features and/or combinations of features for prediction of mobility phenotypes in older adults. PMID- 27653967 TI - Development of an optimized AAV2/5 gene therapy vector for Leber congenital amaurosis owing to defects in RPE65. AB - Leber congenital amaurosis is a group of inherited retinal dystrophies that cause severe sight impairment in childhood; RPE65-deficiency causes impaired rod photoreceptor function from birth and progressive impairment of cone photoreceptor function associated with retinal degeneration. In animal models of RPE65 deficiency, subretinal injection of recombinant adeno-associated virus (AAV) 2/2 vectors carrying RPE65 cDNA improves rod photoreceptor function, and intervention at an early stage of disease provides sustained benefit by protecting cone photoreceptors against retinal degeneration. In affected humans, administration of these vectors has resulted to date in relatively modest improvements in photoreceptor function, even when retinal degeneration is comparatively mild, and the duration of benefit is limited by progressive retinal degeneration. We conclude that the demand for RPE65 in humans is not fully met by current vectors, and predict that a more powerful vector will provide more durable benefit. With this aim we have modified the original AAV2/2 vector to generate AAV2/5-OPTIRPE65. The new configuration consists of an AAV vector serotype 5 carrying an optimized hRPE65 promoter and a codon-optimized hRPE65 gene. In mice, AAV2/5-OPTIRPE65 is at least 300-fold more potent than our original AAV2/2 vector. PMID- 27653969 TI - Multiparametric Analysis of Oncology Drug Screening with Aqueous Two-Phase Tumor Spheroids. AB - Spheroids present a biologically relevant three-dimensional model of avascular tumors and a unique tool for discovery of anticancer drugs. Despite being used in research laboratories for several decades, spheroids are not routinely used in the mainstream drug discovery pipeline primarily due to the difficulty of mass producing uniformly sized spheroids and intense labor involved in handling, drug treatment, and analyzing spheroids. We overcome this barrier using a polymeric aqueous two-phase microtechnology to robotically microprint spheroids of well defined size in standard 384-microwell plates. We use different cancer cells and show that resulting spheroids grow over time and display characteristic features of solid tumors. We demonstrate the feasibility of robotic, high-throughput screening of 25 standard chemotherapeutics and molecular inhibitors against tumor spheroids of three different cancer cell lines. This screening uses over 7000 spheroids to elicit high quality dose-dependent drug responses from spheroids. To quantitatively compare performance of different drugs, we employ a multiparametric scoring system using half-maximum inhibitory concentration (IC50), maximum inhibition (Emax), and area under the dose-response curve (AUC) to take into account both potency and efficacy parameters. This approach allows us to identify several compounds that effectively inhibit growth of spheroids and compromise cellular viability, and distinguish them from moderately effective and ineffective drugs. Using protein expression analysis, we demonstrate that spheroids generated with the aqueous two-phase microtechnology reliably resolve molecular targets of drug compounds. Incorporating this low-cost and convenient to-use tumor spheroid technology in preclinical drug discovery will make compound screening with realistic tumor models a routine laboratory technique prior to expensive and tedious animal tests to dramatically improve testing throughput and efficiency and reduce costs of drug discovery. PMID- 27653968 TI - Examining the Pathologic Adaptation Model of Community Violence Exposure in Male Adolescents of Color. AB - The current study examined a model of desensitization to community violence exposure-the pathologic adaptation model-in male adolescents of color. The current study included 285 African American (61%) and Latino (39%) male adolescents (W1 M age = 12.41) from the Chicago Youth Development Study to examine the longitudinal associations between community violence exposure, depressive symptoms, and violent behavior. Consistent with the pathologic adaptation model, results indicated a linear, positive association between community violence exposure in middle adolescence and violent behavior in late adolescence, as well as a curvilinear association between community violence exposure in middle adolescence and depressive symptoms in late adolescence, suggesting emotional desensitization. Further, these effects were specific to cognitive-affective symptoms of depression and not somatic symptoms. Emotional desensitization outcomes, as assessed by depressive symptoms, can occur in male adolescents of color exposed to community violence and these effects extend from middle adolescence to late adolescence. PMID- 27653970 TI - Association Between Levels of High-Sensitivity C-Reactive Protein and General Psychological Distress Symptoms. PMID- 27653971 TI - The E3 ubiquitin ligase Hace1 is required for early embryonic development in Xenopus laevis. AB - BACKGROUND: HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) regulates a wide variety of cellular processes. It has been shown that one of the targets of HACE1 is the GTP-bound form of the small GTPase Rac1. However, the role of HACE1 in early development remains unknown. RESULTS: In situ hybridization revealed that Xenopus laevis hace1 is specifically expressed in the ectoderm at the blastula and gastrula stages and in the epidermis, branchial arch, kidney, and central nervous system at the tailbud stage. Knockdown of hace1 in Xenopus laevis embryos via antisense morpholino oligonucleotides led to defects in body axis elongation, pigment formation, and eye formation at the tadpole stage. Experiments with Keller sandwich explants showed that hace1 knockdown inhibited convergent extension, a morphogenetic movement known to be crucial for body axis elongation. In addition, time lapse imaging of whole embryos during the neurula stage indicated that hace1 knockdown also delayed neural tube closure. The defects caused by hace1 knockdown were partly rescued by knockdown of rac1. Moreover, embryos expressing a constitutively active form of Rac1 displayed phenotypes similar to those of embryos with hace1 knocked down. CONCLUSIONS: Our results suggest that Xenopus laevis hace1 plays an important role in early embryonic development, possibly via regulation of Rac1 activity. PMID- 27653972 TI - 24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure. AB - In the central nervous system, 24(S)-hydroxycholesterol (24(S)-HC) is an oxysterol synthesized from cholesterol by cholesterol 24-hydroxylase (CYP46A1) encoded by the cyp46a1 gene. In the present study using a rat ex vivo glaucoma model, we found that retinal 24(S)-HC synthesis is facilitated by pressure elevation. Moreover, we found that 24(S)-HC is neuroprotective against pressure mediated retinal degeneration. Quantitative real-time RT-PCR, ELISA, and immunohistochemistry revealed that elevated pressure facilitated the expression of cyp46a1 and CYP46A1. Immunohistochemically, the enhanced expression of CYP46A1 was mainly observed in retinal ganglion cells (RGC). LC-MS/MS revealed that 24(S) HC levels increased in a pressure-dependent manner. Axonal injury and apoptotic RGC death induced by 75 mmHg high pressure was ameliorated by exogenously administered 1 MUM 24(S)-HC. In contrast, voriconazole, a CYP46A1 inhibitor, was severely toxic even at normobaric pressure. Under normobaric conditions, 30 MUM 24(S)-HC was required to prevent the voriconazole-mediated retinal damage. Taken together, our findings indicate that 24(S)-HC is facilitated by elevated pressure and plays a neuroprotective role under glaucomatous conditions, while voriconazole, an antifungal drug, is retinotoxic. 24(S)-HC and related compounds may serve as potential therapeutic targets for protecting glaucomatous eyes from pressure-induced injuries. PMID- 27653974 TI - Impact of oncologist payment method on health care outcomes, costs, quality: a rapid review. AB - BACKGROUND: The incidence of cancer and the cost of its treatment continue to rise. The effect of these dual forces is a major burden on the system of health care financing. One cost containment approach involves changing the way physicians are paid. Payers are testing reimbursement methods such as capitation and prospective payment while also evaluating how the changes impact health outcomes, resource utilization, and quality of care. The purpose of this study is to identify evidence related to physician payment methods' impacts, with a focus on cancer control. METHODS: We conducted a rapid review. This involved defining eligibility criteria, identifying a search strategy, performing study selection according to the eligibility criteria, and abstracting data from included studies. This process was accompanied by a gray literature search for special topics. RESULTS: The incentives in fee-for-service payment systems generally lead to health care services being applied inconsistently because providers practice independently with few systems in place for developing treatment protocols and practice reviews. This inconsistency is pronounced in cancer care because much of the total per patient spending occurs in the last month of life. Some insurers are predicting that this variation can be reduced through the use of prospective or bundled payments combined with decision support systems. Workload, recruitment, and retention are all affected by changes to physician payment models; effects seem to be magnified in the specialist context as their several extra years of training lower their overall supply. CONCLUSIONS: Experimentation with physician payment methods has tended to neglect cancer care providers. Policymakers designing cancer-focused physician reimbursement pilot programs should incorporate quality measurement since very ill patients may receive too little treatment when payment models do not cover oncologists' total costs, e.g., fee-for-service systems whose prices do not account for the possible presence of other diseases. PMID- 27653975 TI - Microstructure, local dynamics, and flow behavior of colloidal suspensions with weak attractive interactions. AB - We present a comprehensive micro- and macrorheological study of the effect of weak depletion attraction (Psidep ~ 1-10 kBT) on dense colloidal suspensions stabilized by short-range repulsive interactions. We used aqueous polymer dispersions as model system and demonstrated the unique capabilities of multiple particle tracking (MPT) to disclose structural changes in such technically important systems exhibiting many characteristic features of hard sphere systems. Below the hard sphere freezing point phic, viscosity increases monotonically with increasing Psidep due to the transition from a fluid to a fluid/crystalline and finally to a gel state. Above phic, increasing attraction strength first results in a viscosity reduction corresponding to the formation of large, permeable crystals and then in a viscosity increase when a network of dense, small crystals forms. The fraction of the fluid and crystal phase, particle concentration in each phase as well as the modulus of the micro-crystals are obtained, the latter decreases with Psidep. Above the colloidal glass transition strong heterogeneities and different local particle mobility in the repulsive and attractive arrested states are found. Particles are trapped in the cage of neighboring particles rather than in an attractive potential well. The intermediate ergodic state exhibits uniform tracer diffusivity. PMID- 27653976 TI - Highly reliable wind-rolling triboelectric nanogenerator operating in a wide wind speed range. AB - Triboelectric nanogenerators are aspiring energy harvesting methods that generate electricity from the triboelectric effect and electrostatic induction. This study demonstrates the harvesting of wind energy by a wind-rolling triboelectric nanogenerator (WR-TENG). The WR-TENG generates electricity from wind as a lightweight dielectric sphere rotates along the vortex whistle substrate. Increasing the kinetic energy of a dielectric converted from the wind energy is a key factor in fabricating an efficient WR-TENG. Computation fluid dynamics (CFD) analysis is introduced to estimate the precise movements of wind flow and to create a vortex flow by adjusting the parameters of the vortex whistle shape to optimize the design parameters to increase the kinetic energy conversion rate. WR TENG can be utilized as both a self-powered wind velocity sensor and a wind energy harvester. A single unit of WR-TENG produces open-circuit voltage of 11.2 V and closed-circuit current of 1.86 MUA. Additionally, findings reveal that the electrical power is enhanced through multiple electrode patterns in a single device and by increasing the number of dielectric spheres inside WR-TENG. The wind-rolling TENG is a novel approach for a sustainable wind-driven TENG that is sensitive and reliable to wind flows to harvest wasted wind energy in the near future. PMID- 27653973 TI - Decoding sORF translation - from small proteins to gene regulation. AB - Translation is best known as the fundamental mechanism by which the ribosome converts a sequence of nucleotides into a string of amino acids. Extensive research over many years has elucidated the key principles of translation, and the majority of translated regions were thought to be known. The recent discovery of wide-spread translation outside of annotated protein-coding open reading frames (ORFs) came therefore as a surprise, raising the intriguing possibility that these newly discovered translated regions might have unrecognized protein coding or gene-regulatory functions. Here, we highlight recent findings that provide evidence that some of these newly discovered translated short ORFs (sORFs) encode functional, previously missed small proteins, while others have regulatory roles. Based on known examples we will also speculate about putative additional roles and the potentially much wider impact that these translated regions might have on cellular homeostasis and gene regulation. PMID- 27653977 TI - Imagery May Arise from Associations Formed through Sensory Experience: A Network of Spiking Neurons Controlling a Robot Learns Visual Sequences in Order to Perform a Mental Rotation Task. AB - Mental imagery occurs "when a representation of the type created during the initial phases of perception is present but the stimulus is not actually being perceived." How does the capability to perform mental imagery arise? Extending the idea that imagery arises from learned associations, we propose that mental rotation, a specific form of imagery, could arise through the mechanism of sequence learning-that is, by learning to regenerate the sequence of mental images perceived while passively observing a rotating object. To demonstrate the feasibility of this proposal, we constructed a simulated nervous system and embedded it within a behaving humanoid robot. By observing a rotating object, the system learns the sequence of neural activity patterns generated by the visual system in response to the object. After learning, it can internally regenerate a similar sequence of neural activations upon briefly viewing the static object. This system learns to perform a mental rotation task in which the subject must determine whether two objects are identical despite differences in orientation. As with human subjects, the time taken to respond is proportional to the angular difference between the two stimuli. Moreover, as reported in humans, the system fills in intermediate angles during the task, and this putative mental rotation activates the same pathways that are activated when the system views physical rotation. This work supports the proposal that mental rotation arises through sequence learning and the idea that mental imagery aids perception through learned associations, and suggests testable predictions for biological experiments. PMID- 27653978 TI - A double-lyophilization method for the preparation of CS/GO-COOH scaffold and its application in blood detoxification. AB - The accumulation of uremic toxins in blood might induce chronic renal failure (CRF). The incidence of CRF was as high as 10%. The traditional therapy for CRF was hemodialysis, which was more effective to remove small molecules, such as urea and creatinine. However, this detoxification method ignored the tissue functional adaption due to the retention of macromolecule uremic toxins. To solve this problem, this paper developed a new kind of chitosan/carboxyl graphite oxide (CS/GO-COOH) scaffold via a double-lyophilization method. Then, this synthetic scaffold was characterized by Fourier transform infrared spectroscopy, scanning electron microscope, hydrophilic test, mechanical property, and in vitro detoxification test. Covalent bonding and hydrogen bonding were formed, indicating the strong interactions between CS and GO-COOH. There were interconnected networks in the synthesized scaffold. The mechanical test suggested that the GO-2500 scaffold had excellent mechanical strength, which was 7.41 +/- 0.82 MPa with 25% shrink. What is more, GO-2500 could totally rebound within 1s, after compressed to 90% shrink. The rates of GO-2500 were 1587 +/- 60 and 246 +/- 10% according to the water uptake and retention data, respectively. Furthermore, the detoxification of GO-2500 to urea, creatinine, VB12, and beta2-m were 67.59 +/- 2.31, 39.67 +/- 2.95, 31.51 +/- 2.62, and 83.82 +/- 7.76 mg/g, respectively. The resulting CS/GO-COOH scaffold held great potential for the detoxification of uremic toxins. PMID- 27653979 TI - Complete mitochondrial genomes of Trisidos kiyoni and Potiarca pilula: Varied mitochondrial genome size and highly rearranged gene order in Arcidae. AB - We present the complete mitochondrial genomes (mitogenomes) of Trisidos kiyoni and Potiarca pilula, both important species from the family Arcidae (Arcoida: Arcacea). Typical bivalve mtDNA features were described, such as the relatively conserved gene number (36 and 37), a high A + T content (62.73% and 61.16%), the preference for A + T-rich codons, and the evidence of non-optimal codon usage. The mitogenomes of Arcidae species are exceptional for their extraordinarily large and variable sizes and substantial gene rearrangements. The mitogenome of T. kiyoni (19,614 bp) and P. pilula (28,470 bp) are the two smallest Arcidae mitogenomes. The compact mitogenomes are weakly associated with gene number and primarily reflect shrinkage of the non-coding regions. The varied size in Arcidae mitogenomes reflect a dynamic history of expansion. A significant positive correlation is observed between mitogenome size and the combined length of cox1 3, the lengths of Cytb, and the combined length of rRNAs (rrnS and rrnL) (P < 0.001). Both protein coding genes (PCGs) and tRNA rearrangements is observed in P. pilula and T. kiyoni mitogenomes. This analysis imply that the complicated gene rearrangement in mitochondrial genome could be considered as one of key characters in inferring higher-level phylogenetic relationship of Arcidae. PMID- 27653980 TI - Technique to 'Map' Chromosomal Mosaicism at the Blastocyst Stage. AB - The purpose of this study was to identify a technique that allows for comprehensive chromosome screening (CCS) of individual cells within human blastocysts along with the approximation of their location in the trophectoderm relative to the inner cell mass (ICM). This proof-of-concept study will allow for a greater understanding of chromosomal mosaicism at the blastocyst stage and the mechanisms by which mosaicism arises. One blastocyst was held by a holding pipette and the ICM was removed. While still being held, the blastocyst was further biopsied into quadrants. To separate the individual cells from the biopsied sections, the sections were placed in calcium/magnesium-free medium with serum for 20 min. A holding pipette was used to aspirate the sections until individual cells were isolated. Individual cells from each section were placed into PCR tubes and prepped for aCGH. A total of 18 cells were used for analysis, of which 15 (83.3%) amplified and provided a result and 3 (16.7%) did not. Fifteen cells were isolated from the trophectoderm; 13 (86.7%) provided an aCGH result, while 2 (13.3%) did not amplify. Twelve cells were euploid (46,XY), while 1 was complex abnormal (44,XY), presenting with monosomy 7, 10, 11, 13, and 19, and trisomy 14, 15, and 21. A total of 3 cells were isolated from the ICM; 2 were euploid (46,XY) and 1 did not amplify. Here, we expand on a previously published technique which disassociates biopsied sections of the blastocyst into individual cells. Since the blastocyst sections were biopsied in regard to the position of the ICM, it was possible to reconstruct a virtual image of the blastocyst while presenting each cell's individual CCS results. PMID- 27653981 TI - Cerebrospinal fluid-induced retardation of amyloid beta aggregation correlates with Alzheimer's disease and the APOE epsilon4 allele. AB - Misfolding and aggregation of amyloid beta (Abeta) are key features of Alzheimer's disease (AD) pathogenesis, but the molecular events controlling this process are not known in detail. In vivo, Abeta aggregation and plaque formation occur in the interstitial fluid of the brain extracellular matrix. This fluid communicates freely with cerebrospinal fluid (CSF). Here, we examined the effect of human CSF on Abeta aggregation kinetics in relation to AD diagnosis and carrier status of the apolipoprotein E (APOE) epsilon4 allele, the main genetic risk factor for sporadic AD. The aggregation of Abeta was inhibited in the presence of CSF and, surprisingly, the effect was more pronounced in APOE epsilon4 carriers. However, by fractionation of CSF using size exclusion chromatography, it became evident that it was not the ApoE protein itself that conveyed the inhibition, since the retarding species eluted at lower volume, corresponding to a much higher molecular weight, than ApoE monomers. Cholesterol quantification and immunoblotting identified high-density lipoprotein particles in the retarding fractions, indicating that such particles may be responsible for the inhibition. These results add information to the yet unresolved puzzle on how the risk factor of APOE epsilon4 functions in AD pathogenesis. PMID- 27653982 TI - Cancer and treatment-related symptoms are associated with mobility disability in women with ovarian cancer: A cross-sectional study. AB - OBJECTIVE: To examine the prevalence of symptom-related mobility disability and identify specific symptoms and other factors associated with mobility disability among a national sample of ovarian cancer (OC) survivors. METHODS: Descriptive, correlational secondary analysis of a National Ovarian Cancer Coalition mailed survey of women with a history of OC (n=713). We used the Symptom Representation Questionnaire (SRQ), the MD Anderson Symptom Inventory (MDASI) Interference Scale, and medical and demographic information to determine prevalence of symptom related mobility disability. We constructed a multiple linear regression model to determine the relative contributions of specific symptoms and other factors to mobility disability. RESULTS: A majority of the sample (60.0%) reported symptom related mobility disability. Independent predictors included: > one comorbidity (beta=0.112, p=0.001), active OC (beta=0.111, p=0.037), abdominal bloating (beta=0.097, p=0.006), fatigue (beta=0.314, p<0.001), lack of appetite (beta=0.072, p=0.045), numbness/tingling (beta=0.134, p<0.001), and pain (beta=0.194, p<0.001). The model explained 41.5% of the variance in symptom related mobility disability (R2=0.415). Unexpectedly, age (beta=-0.028, p=0.412) and current chemotherapy (beta=0.107, p=0.118) were not significant predictors. CONCLUSIONS: Symptom-related mobility disability is common among women with OC and is associated with medical comorbidities, abdominal bloating, fatigue, lack of appetite, numbness/tingling, and pain. Longitudinal research should clarify the relationship of these symptoms to mobility disability and determine whether effective symptom management minimizes disability. PMID- 27653985 TI - RACK1 is required for adipogenesis. AB - Adipose tissue plays a critical role in metabolic diseases and the maintenance of energy homeostasis. RACK1 has been identified as an adaptor protein involved in multiple intracellular signal transduction pathways and diseases. However, whether it regulates adipogenesis remains unknown. Here, we reported that RACK1 is expressed in 3T3-L1 cells and murine white adipose tissue and that RACK1 knockdown by shRNA profoundly suppressed adipogenesis by reducing the expression of PPAR-gamma and C/EBP-beta. Depletion of RACK1 increased beta-catenin protein levels and activated Wnt signaling. Furthermore, RACK1 knockdown also suppressed the PI3K-Akt-mTOR-S6K signaling pathway by reducing the PI3K p85alpha, pAkt T473, and S6K p70. Taken together, these results demonstrate that RACK1 is a novel factor required for adipocyte differentiation by emerging Wnt/beta-catenin signaling and PI3K-Akt-mTOR-S6K signaling pathway(s). PMID- 27653986 TI - NaV-igating the MAP from PACAP to excitement. Focus on "Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability". PMID- 27653984 TI - Defects in brainstem neurons associated with breathing and motor function in the Mecp2R168X/Y mouse model of Rett syndrome. AB - Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder caused mostly by disruption of the MECP2 gene. Among several RTT-like mouse models, one of them is a strain of mice that carries an R168X point mutation in Mecp2 and resembles one of the most common RTT-causing mutations in humans. Although several behavioral defects have previously been found in the Mecp2R168X/Y mice, alterations in nerve cells remain unknown. Here we compare several behavioral and cellular outcomes between this Mecp2R168X/Y model and a widely used Mecp2Bird/Y mouse model. With lower body weight and shorter lifespan than their wild-type littermates, the Mecp2R168X/Y mice showed impairments of breathing and motor function. Thus we studied brainstem CO2-chemosensitive neurons and propriosensory cells that are associated with these two functions, respectively. Neurons in the locus coeruleus (LC) of both mutant strains showed defects in their intrinsic membrane properties, including changes in action potential morphology and excessive firing activity. Neurons in the mesencephalic trigeminal nucleus (Me5) of both strains displayed a higher firing response to depolarization than their wild-type littermates, likely attributable to a lower firing threshold. Because the increased excitability in LC and Me5 neurons tends to impact the excitation inhibition balances in brainstem neuronal networks as well as their associated functions, it is likely that the defects in the intrinsic membrane properties of these brainstem neurons contribute to the breathing abnormalities and motor dysfunction. Furthermore, our results showing comparable phenotypical outcomes of Mecp2R168X/Y mice with Mecp2Bird/Y mice suggest that both strains are valid animal models for RTT research. PMID- 27653983 TI - Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis. AB - In the shark rectal gland (SRG), apical chloride secretion through CFTR channels is electrically coupled to a basolateral K+ conductance whose type and molecular identity are unknown. We performed studies in the perfused SRG with 17 K+ channel inhibitors to begin this search. Maximal chloride secretion was markedly inhibited by low-perfusate pH, bupivicaine, anandamide, zinc, quinidine, and quinine, consistent with the properties of an acid-sensitive, four-transmembrane, two-pore-domain K+ channel (4TM-K2P). Using PCR with degenerate primers to this family, we identified a TASK-1 fragment in shark rectal gland, brain, gill, and kidney. Using 5' and 3' rapid amplification of cDNA ends PCR and genomic walking, we cloned the full-length shark gene (1,282 bp), whose open reading frame encodes a protein of 375 amino acids that was 80% identical to the human TASK-1 protein. We expressed shark and human TASK-1 cRNA in Xenopus oocytes and characterized these channels using two-electrode voltage clamping. Both channels had identical current-voltage relationships (outward rectifying) and a reversal potential of 90 mV. Both were inhibited by quinine, bupivicaine, and acidic pH. The pKa for current inhibition was 7.75 for shark TASK-1 vs. 7.37 for human TASK-1, values similar to the arterial pH for each species. We identified this protein in SRG by Western blot and confocal immunofluorescent microscopy and detected the protein in SRG and human airway cells. Shark TASK-1 is the major K+ channel coupled to chloride secretion in the SRG, is the oldest 4TM 2P family member identified, and is the first TASK-1 channel identified to play a role in setting the driving force for chloride secretion in epithelia. The detection of this potassium channel in mammalian lung tissue has implications for human biology and disease. PMID- 27653987 TI - Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer's disease, mild cognitive impairment, or healthy controls: a two year follow-up study. AB - BACKGROUND: alpha-Synuclein has been proposed as a potential biomarker for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, results from alpha-synuclein measurements in cerebrospinal fluid (CSF) have been inconclusive, and to our knowledge, longitudinal studies of changes prior to the AD diagnosis have not been investigated. METHODS: Levels of alpha-synuclein at baseline and after one and two years were measured in CSF, by enzyme-linked immunosorbent assay. Twenty-six patients with early AD (AD-AD), 48 patients with aMCI, subdivided as 23 that developed AD during follow-up (MCI-AD), and 25 that did not (MCI-MCI), and 25 healthy control individuals, were included. One-way ANOVA was applied to compare mean alpha-synuclein baseline values between all four study groups, and a linear mixed model was used to compare mean change over time between the three patient groups. Linear associations between alpha synuclein and amyloid-beta 1-42 (Abeta42), amyloid-beta 1-40 (Abeta40), total tau and phosphorylated tau were also examined. RESULTS: A large variation in individual alpha-synuclein CSF levels was observed, particularly in the MCI-AD group. No significant differences were found in mean alpha-synuclein levels between all the study groups at baseline. When using a linear mixed model, no significant differences were found at follow-up for estimated mean changes between the patient groups. MCI-AD patients with short duration of symptoms prior to inclusion in the study (<=2 years) had considerably higher mean CSF alpha synuclein levels compared to patients with a longer symptom duration (802.2 vs. 442.8 pg/mL, p = 0.01). No such difference was seen in the MCI-MCI or AD-AD groups. Significant linear associations (p < 0.0005) between alpha-synuclein and Abeta40, total tau and phosphorylated tau were found. CONCLUSION: The observed difference in mean CSF alpha-synuclein level according to duration of symptoms in the MCI-AD group, may be an indication of changes related to disease progression. However, the lack of significant differences between groups, as well as the large individual variation in CSF levels of alpha-synuclein in the present study, suggest that alpha-synuclein is not a useful biomarker for AD. PMID- 27653988 TI - Transitioning From Cigarettes to Electronic Cigarettes Increases Alcohol Consumption. AB - OBJECTIVE: Electronic cigarettes (e-cigs) are a nicotine delivery device that have recently been linked to alcohol use. Many individuals that smoke cigarettes transition to e-cigs as an alternative to cigarette use, despite potential negative health effects of e-cigs. No research to date has examined how former smokers that have transitioned to e-cigs differ from former smokers that do not use e-cigs, particularly in relation to alcohol use. Further, no research has examined how former smokers that use e-cigs regularly or socially may differ in alcohol consumption. METHOD: Using an online community dwelling sample (Former smokers N = 198, mean age = 34.70, SD = 11.45, 56.1% female, 78.3% Caucasian, 37.9% e-cig users), the present study assessed smoking status and alcohol use, with the latter assessed using a timeline followback calendar and the alcohol use disorder identification test (AUDIT). RESULTS: In all former smokers, total drinks (b = 4.01, p = 0.02) and average drinks per drinking day (b = 0.61, p =.01) were both related to e-cig use status, with e-cig users reporting higher alcohol consumption. Among e-cig using former smokers, social users, but not regular users, showed positive relationships with AUDIT scores, b = 1.90, p =.02, total drinks, b = 9.12, p <.001, average drinks, b = 0.98, p =.006, and hazardous drinking status, OR = 3.21, p =.01. CONCLUSIONS: Findings suggest that: (1) former smokers who use e-cigs may have a potential for higher alcohol use; and (2) those who use e-cigs socially may be at heightened risk for hazardous patterns of alcohol consumption. This should be taken into consideration by healthcare providers. PMID- 27653990 TI - The use of carbon dioxide angiography for renal sympathetic denervation: a technical report. AB - OBJECTIVE: Hypertension is the leading attributable cause of cardiovascular mortality worldwide. Patients with hypertension have multiple comorbidities including high rates of concomitant renal disease. Current pharmacological approaches are inadequate in the treatment of resistant hypertension. Renal sympathetic denervation (RDN) has been shown to effectively treat resistant hypertension. The traditional use of iodinated contrast in RDN is contraindicated in patients with significant renal insufficiency. In patients with renal impairment, carbon dioxide (CO2) can be used as an alternative contrast material for RDN. This article describes the technical aspects of RDN using CO2 angiography. METHODS: Our centre is experienced in the innovative RDN procedure using CO2 angiography. We describe the protocol for CO2 angiography for RDN using a home-made CO2 delivery system and the SymplicityTM (Minneapolis MN 55432 USA) catheter (Medtronic) device. RESULTS: CO2 angiography is an excellent alternative to iodinated contrast for RDN procedures. CONCLUSION: CO2 angiography for RDN is a safe and effective alternative to iodinated contrast. RDN using CO2 angiography is an easy and feasible procedure that can be used in patients with renal insufficiency or iodinated contrast allergies. Advances in knowledge: There is a paucity of descriptive reports for CO2 angiography for RDN and we provide details of the optimal protocol for the procedure. In particular, we describe the use of a Symplicity SpyralTM catheter (Medtronic), which has not been reported to date for use in this procedure. PMID- 27653991 TI - Language lateralization of a bilingual person with epilepsy using a combination of fMRI and neuropsychological assessment findings. AB - This report describes the findings of language functional magnetic resonance imaging (fMRI) in a left-handed Urdu and English speaker with right hemisphere originating epilepsy and unclear language dominance. fMRI is a reliable method for determining hemispheric language dominance in presurgical planning. However, the effects of bilingualism on language activation depend on many factors including age of acquisition and proficiency in the tested language, and morphological properties of the language itself. This case demonstrates that completing fMRI in both spoken languages and interpreting the results within the context of a neuropsychological assessment are essential in arriving at accurate conclusions about language distribution in bilingual patients. PMID- 27653992 TI - Generalized Potential Energy Finite Elements for Modeling Molecular Nanostructures. AB - The potential energy of molecules and nanostructures is commonly calculated in the molecular mechanics formalism by superimposing bonded and nonbonded atomic energy terms, i.e. bonds between two atoms, bond angles involving three atoms, dihedral angles involving four atoms, nonbonded terms expressing the Coulomb and Lennard-Jones interactions, etc. In this work a new, generalized numerical simulation is presented for studying the mechanical behavior of three-dimensional nanostructures at the atomic scale. The energy gradient and Hessian matrix of such assemblies are usually computed numerically; a potential energy finite element model is proposed herein where these two components are expressed analytically. In particular, generalized finite elements are developed that express the interactions among atoms in a manner equivalent to that invoked in simulations performed based on the molecular dynamics method. Thus, the global tangent stiffness matrix for any nanostructure is formed as an assembly of the generalized finite elements and is directly equivalent to the Hessian matrix of the potential energy. The advantages of the proposed model are identified in terms of both accuracy and computational efficiency. In the case of popular force fields (e.g., CHARMM), the computation of the Hessian matrix by implementing the proposed method is of the same order as that of the gradient. This analysis can be used to minimize the potential energy of molecular systems under nodal loads in order to derive constitutive laws for molecular systems where the entropy and solvent effects are neglected and can be approximated as solids, such as double stranded DNA nanostructures. In this context, the sequence dependent stretch modulus for some typical base pairs step is calculated. PMID- 27653994 TI - Synthetic Biology: Innovative approaches for pharmaceutics and drug delivery. PMID- 27653993 TI - Higher education in gerontology: A comparison of master's programs in Japan, Taiwan, and Turkey. AB - As of 2015, there is only one master's program of gerontology acknowledged by each of the following countries: Japan, Taiwan, and Turkey. All three programs have fewer than 15 years of history. These three countries differ in society types based on the proportion of older adults, rate of population aging, and population size. However, in terms of gerontological education, they seem to share great commonalities. Common challenges are a lack of awareness of the field of gerontology, insufficient numbers of gerontology programs and faculty members to produce trained gerontologists within society, and the inadequacy of opportunities for trained gerontologists to play an active role in various fields. This study intends not only to compare the differences and similarities among three countries and programs, but also to elucidate characteristics of a unique gerontology program in each country and identify challenges and possibilities from the perspective of gerontological educators. PMID- 27653995 TI - Residue Analysis of Benzobicyclon in Soil and Sediment Samples by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry. AB - A reliable and rapid method was developed to determine benzobicyclon residue in different soil and sediment samples. After extraction via a modified quick, easy, cheap, effective, rugged, and safe method, samples were purified by SPE cleanup with HLB cartridges. Quantitative determination was performed by ultra-HPLC (UPLC)-tandem MS (MS/MS) in electrospray positive ionization and multiple reaction monitoring modes. When samples were fortified at concentrations of 5, 50, and 500 ug/L, recoveries of 80.2 to 114.5% were obtained, with the repeatability (intraday RSDr) and reproducibility (interday RSDR) <14.1 and <21.4%, respectively. The instrumental LODs and LOQs for matrix-matched standards and the method LOQs for sample test were 0.19-1.34 MUg/L, 0.64-4.48 MUg/L, and 0.32-2.24 MUg/kg, respectively. The linear range was 5-1000 MUg/L (R2 > 0.99). The established UPLC-MS/MS method was applied in the detection of benzobicyclon in real soil samples, which were collected during the supervised field trial. Results showed that the maximum concentration of benzobicyclon in the soil was 4.87 mg/kg and its degradation half-life (t0.5) was 6.7 days. Generally, the proposed method could be an effective tool for controlling and monitoring the risks posed by benzobicyclon to human health and environmental safety. PMID- 27653996 TI - Comment on "Multiple Independent Binding Sites for Small-Molecule Inhibitors on the Oncoprotein c-Myc". PMID- 27653998 TI - Special Section Guest Editorial:Clinical near-infrared spectroscopy and imaging of the brain. PMID- 27653997 TI - Soft Surfaces for Fast Characterization and Positioning of Scanning Electrochemical Microscopy Nanoelectrode Tips. AB - The testing of nanoelectrode tips for scanning electrochemical microscopy (SECM) is a slow and cumbersome task that often results in untimely electrode breakage due to crashing against a substrate. Here, we evaluated approach curves of nano- and microelectrodes to soft surfaces using SECM for a rapid and more convenient characterization and positioning protocol. Soft surfaces consisted of either a submerged argon bubble or a thin polydimethylsiloxane (PDMS) layer. While approach curves to Ar bubbles in the presence of a surfactant were promising for the characterization of microelectrode tips, their performance with nanoelectrodes was deficient. In contrast, approach curves to PDMS films allowed the rapid positioning of nanoelectrodes as small as 30 nm radius at speeds up to 5 MUm/s without the risk of breakage. The nanoelectrodes were able to approach the polymer films multiple times without affecting their electrochemical performance. Furthermore, using a half-coated substrate with PDMS, nanoelectrodes could be retracted and positioned very close to the bare, hard substrate for characterization with traditional approach curves. We estimate time savings on tip characterization/positioning on the order of 10- to 100-fold. This simple procedure is easily implemented without the requirement of additional devices supplementing existing commercial SECM instruments. PMID- 27653999 TI - Comprehensive vascular imaging using optical coherence tomography-based angiography and photoacoustic tomography. AB - Studies have proven the relationship between cutaneous vasculature abnormalities and dermatological disorders, but to image vasculature noninvasively 15% in both EuroSCORE and STS score) was associated with reduced 1-year survival (P = 0.046). Thus, patients treated via IL/Fm access had acceptable outcome regardless of preoperative risk levels while patients with low surgical risk (<15%) had favorable outcome irrespective of access route. Since the remaining patients with combined risk factors, high preoperative risk level (>15%) requiring alternative access, had a prohibitive risk in our experience, they might have been considered untreatable or not amenable even to TAVI and offered medical or alternative managements. PMID- 27654025 TI - Human and server docking prediction for CAPRI round 30-35 using LZerD with combined scoring functions. AB - We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues' spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, that is whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. Proteins 2017; 85:513-527. (c) 2016 Wiley Periodicals, Inc. PMID- 27654028 TI - Lack of immunocytological GD2 expression on neuroblastoma cells in bone marrow at diagnosis, during treatment, and at recurrence. AB - BACKGROUND: Loss of disialoganglioside 2 (GD2) expression in neuroblastoma (NB) bone marrow cells has been reported in rare cases. This study investigated prospectively the frequency and the patterns of visible GD2 loss at diagnosis, during treatment, and at recurrence. METHODS: Bone marrow aspirates of patients with new or recurrent stage 4 and 4S NB diagnosed between January 1, 2002 and August 31, 2013 were investigated in parallel by cytology and GD2 immunocytology. Complete negative immunostaining was defined if staining was absent in all and partial if absent in a portion and/or in case of atypical faint staining. RESULTS: Of 1,261 investigated trial patients of all stages, 474 had unequivocal cytological bone marrow infiltration at initial diagnosis. Thirty-seven patients had tumor cells with complete or partial negative GD2 staining at initial diagnosis, nine during chemotherapy, and 11 at recurrence (altogether 12.0%). The percentage of GD2 negativity in stages 4 and 4S were similar (13% and 9%, respectively). Complete negativity was seen in 14 and partial in 43 cases. Twenty one cases changed from positive to negative (15 to partial and six to complete) and three cases from negative to positive staining (two to partial and one to complete). The GD2 negative and positive groups were not different regarding tumor sites, molecular characteristics, histology, and tumor markers. Children with stage 4 and GD2 negativity tended to be older at diagnosis (42 vs. 32 months, P = 0.056). Event-free survival and overall survival comparing negative versus positive staining did not show any differences. CONCLUSIONS: Complete or partial lack of GD2 staining on NB cells in bone marrow is more frequent than currently recognized. PMID- 27654029 TI - Limited gene dispersal and spatial genetic structure as stabilizing factors in an ant-plant mutualism. AB - Comparative studies of the population genetics of closely associated species are necessary to properly understand the evolution of these relationships because gene flow between populations affects the partners' evolutionary potential at the local scale. As a consequence (at least for antagonistic interactions), asymmetries in the strength of the genetic structures of the partner populations can result in one partner having a co-evolutionary advantage. Here, we assess the population genetic structure of partners engaged in a species-specific and obligatory mutualism: the Neotropical ant-plant, Hirtella physophora, and its ant associate, Allomerus decemarticulatus. Although the ant cannot complete its life cycle elsewhere than on H. physophora and the plant cannot live for long without the protection provided by A. decemarticulatus, these species also have antagonistic interactions: the ants have been shown to benefit from castrating their host plant and the plant is able to retaliate against too virulent ant colonies. We found similar short dispersal distances for both partners, resulting in the local transmission of the association and, thus, inbred populations in which too virulent castrating ants face the risk of local extinction due to the absence of H. physophora offspring. On the other hand, we show that the plant populations probably experienced greater gene flow than did the ant populations, thus enhancing the evolutionary potential of the plants. We conclude that such levels of spatial structure in the partners' populations can increase the stability of the mutualistic relationship. Indeed, the local transmission of the association enables partial alignments of the partners' interests, and population connectivity allows the plant retaliation mechanisms to be locally adapted to the castration behaviour of their symbionts. PMID- 27654030 TI - Novel technology to help understand the context of physical activity and sedentary behaviour. AB - When used in large, national surveillance programmes, objective measurement tools provide prevalence estimates of low physical activity guideline compliance and high amounts of sedentary time. There are undoubtedly a plethora of reasons for this but one possible contributing factor is the current lack of behavioural context offered by accelerometers and posture sensors. Context includes information such as where the behaviour occurs, the type of activity being performed and is vital in allowing greater refinement of intervention strategies. Novel technologies are emerging with the potential to provide this information. Example data from three ongoing studies is used to illustrate the utility of these technologies. Study one assesses the concurrent validity of electrical energy monitoring and wearable cameras as measures of television viewing. This study found that on average the television is switched on for 202 min d-1 but is visible in just 90 min of wearable camera images with a further 52 min where the participant is in their living room but the television is not visible in the image. Study two utilises indoor location monitoring to assess where older adult care home residents accumulate their sedentary time. This study found that residents were highly sedentary (sitting for an average of 720 min d-1) and spent the majority of their time in their own rooms with more time spent in communal areas in the morning than in the afternoon. Lastly, study three discusses the use of proximity sensors to quantify exposure to a height adjustable desk. These studies are example applications of this technology, with many other technologies available and applications possible. The adoption of these technologies will provide researchers with a more complete understanding of the behaviour than has previously been available. PMID- 27654031 TI - Sexual dysfunction in women with migraine and tension-type headaches. AB - Primary headaches (PHAs) prominently affect the performance and life quality of people. Sexual dysfunction (SD) is an important health problem caused by several factors. This study aimed to compare the sexual function of women who have PHAs. Forty-one female patients who were diagnosed with migraine, 39 female patients who were diagnosed with tension-type headache (TTHA) and 41 healthy subjects were included in study. Sexual function of the cases were evaluated by using the 'Female Sexual Function Index (FSFI)'. Beck Depression Scale was applied to subjects and those who were diagnosed with depression were excluded from the study. SD was detected in both the migraine and TTHA groups. FSFI subgroup scores were statistically significantly lower in the migraine and TTHA groups compared with the control group. No significant differences were detected between the migraine and TTHA groups in terms of FSFI and its components. In addition, no significant differences were detected between the blood prolactin levels or SD and headache. It was concluded that primary headaches (which are chronic diseases) itself may cause SD in female patients with migraine and TTHA independently of factors that may cause development of SD such as comorbid condition, depression, drug use and age. PMID- 27654032 TI - Erectile dysfunction in young men with type 1 diabetes. AB - Erectile dysfunction (ED) is a common comorbidity of diabetes mellitus, but few studies investigated its prevalence in type 1 diabetes. The objective of this study was to evaluate the prevalence and correlates of ED in young men with type 1 diabetes treated with different intensive insulin regimens. The study population included 151 type 1 diabetic men, aged 18-35 years, and 60 healthy age matched controls. Ninety-four men were treated with multiple daily injections of insulin (MDI), and the remaining 71 with continuous subcutaneous insulin infusion (CSII). All participants in the study completed the International Index of Erectile function (IIEF-5), and other validated multiple-choice questionnaires assessing quality of life, physical activity, depressive symptoms and diabetes related problems. The overall prevalence of ED was higher in diabetic men (37%), as compared with controls (6%, P<0.001). ED prevalence rates were similar in both MDI (36%) and CSII (39%) groups (P=0.326); both were higher compared with controls (P<0.001 for both). More than half of diabetic men (58%) had mild ED. Compared with men without ED, diabetic men with ED showed lower weight, body mass index, fasting glucose, insulin dose and high-density lipoprotein cholesterol levels, and higher self-rating depression score (SRDS). In the multiple regression analysis only the SRDS (P=0.032) were independent predictors of IIEF-5 score in the overall diabetic men. Young men with type 1 diabetes treated with MDI or CSII show a higher prevalence of ED, as compared with healthy age-matched men. Depression was associated with ED in diabetic population. PMID- 27654033 TI - Effects of the start time of glycemic control on erectile function in streptozotocin-induced diabetic rats. AB - Diabetes-induced ED correlates with diabetes duration and glycemic control. This study evaluated the effect of glycemic control start time on erectile function in streptozotocin-induced diabetic rats. Rats were divided into normal controls (C); untreated diabetic rats (DM); and rats treated after 7 weeks (7W), and 10 weeks (10W) from DM. Treated diabetic rats received a timed daily injection of insulin. After 14 weeks of lab-controlled diabetes, experiments were performed. Group DM showed the ratio of intracavernosal pressure, significantly lower than other groups (10W vs DM; P<0.001). Groups 7W and 10W responded similarly, but did not recover to normal level (group C vs 7W; P<0.001). The percentage of alpha-smooth muscle actin increased more with earlier start times, and group DM's percentages decreased significantly (group 10W vs DM; P<0.001). Apoptosis recovered significantly only in group 7W, comparable to group C. As start times became earlier, for all molecules (eNOS, Akt, MYPT1 and PECAM-1), treatment groups' results neared those of group C. In conclusion, erectile function of diabetic rats recovered closer to normal controls if diabetic treatment started earlier. And the level of glycemic control was expected to be more important than the start time of diabetic treatment. PMID- 27654034 TI - An experimental study: evaluating the tissue structure of penis with 2D ShearWaveTM Elastography. AB - The aim of this study was to investigate the feasibility of two-dimensional ShearWaveTM Elastography (2D-SWE) on evaluating the change of tissue structure of penis. Twenty healthy male Sprague Dawley rats were divided into penis-developed group (PDG, 52 weeks) and penis-underdeveloped group (PUDG, 5 weeks). The ultrafast ultrasound device-Aixplorer(r) (SuperSonic Imagine) was used for 2D-SWE imaging of the penis, the measurement index was shear wave stiffness (SWS, kPa). All rat penises were cut off immediately after ultrasonic examination. After paraffin embedding, slicing and hematoxylin-eosin staining, the tissue structure of the penis was observed under light microscope. SWS of all rat penises were measured successfully. The results showed that SWS of PDG was significantly lower than PUDG (P=0.008). At the same time, the pathological results found that there were significant differences in the tissue structures (sinusoids, smooth muscle cells and fibrocytes) of the penises between the two groups. These results suggest that there are significant differences in SWS between different tissue structures of penis. 2D-SWE is expected to be used on the etiological diagnosis of erectile dysfunction by serving as a new noninvasive method of evaluating the change of tissue structure of penis. PMID- 27654035 TI - Sexual function and hormonal profiles in women with and without polycystic ovary syndrome: a population-based study. AB - There is no consensus regarding the impact of polycystic ovary syndrome (PCOS) and its hormonal profile on sexual function of affected women; majority of data documented are not population based and there is a lack of studies investigating the association between hormonal profiles with sexual function in women with PCOS. We aimed to compare the sexual function of PCOS women with controls in a population-based study based on their hormonal profiles. In this cross-sectional study, sexual function (using the Female Sexual Function Index (FSFI) questionnaire) and hormonal profiles were determined in 63 PCOS subjects and 216 healthy women (controls); aged 18-45 years. A comparison of PCOS women and controls showed no statistically significant difference in total FSFI and each of its specific domain scores. There were significant positive correlations between dehydroepiandrosterone sulfate and total FSFI, orgasm and satisfaction domains in controls (r=0.156, r=0.206, r=0.275, respectively). No significant correlations between hormonal profiles and FSFI scores were found in the PCOS group, except for prolactin and orgasm (r=-0.250). In conclusion, sexual function did not differ between PCOS women and controls. High levels of androgens in women with PCOS were not associated with an improvement in sexual function. PMID- 27654036 TI - Sleep Duration and Child Well-Being: A Nonlinear Association. AB - Although numerous studies among adults have shown a U-shaped association between sleep duration and health outcomes, fewer studies have investigated the theory that children also have an optimal sleep duration range, with both lower and upper limits. We evaluated whether children's sleep duration at ages 5 and 9 has a U-shaped association with both behavioral problems and physical health at age 9. We analyzed data from 1,965 participants in a longitudinal birth cohort, the Fragile Families and Child Wellbeing Study. This sample of children was 52% male and approximately 22% non-Hispanic White, 52% non-Hispanic Black, 23% Hispanic, and 3% some other race/ethnicity. The child's primary caregiver reported the predictor of interest: sleep duration at age 5 and age 9. Both children and primary caregivers reported on outcomes of the child's behavior problems (internalizing and externalizing) and overall physical health. We found that the association between children's sleep duration and well-being was typically nonlinear and U-shaped. Adjusting for their sleep duration at age 5, children who sleep either too much or too little at age 9 had higher levels of behavior problems and scored lower on a global measure of physical health. These nonlinear patterns were similar whether children or primary caregivers reported child outcomes, with the exception that there was a linear and increasing association of longer sleep duration and caregiver-rated child health. This study highlights that both short and long sleep duration may be risk factors for adverse behavioral and health outcomes in school-age children. PMID- 27654037 TI - An Extended Multilocus Sequence Typing (MLST) Scheme for Rapid Direct Typing of Leptospira from Clinical Samples. AB - BACKGROUND: Rapid typing of Leptospira is currently impaired by requiring time consuming culture of leptospires. The objective of this study was to develop an assay that provides multilocus sequence typing (MLST) data direct from patient specimens while minimising costs for subsequent sequencing. METHODOLOGY AND FINDINGS: An existing PCR based MLST scheme was modified by designing nested primers including anchors for facilitated subsequent sequencing. The assay was applied to various specimen types from patients diagnosed with leptospirosis between 2014 and 2015 in the United Kingdom (UK) and the Lao Peoples Democratic Republic (Lao PDR). Of 44 clinical samples (23 serum, 6 whole blood, 3 buffy coat, 12 urine) PCR positive for pathogenic Leptospira spp. at least one allele was amplified in 22 samples (50%) and used for phylogenetic inference. Full allelic profiles were obtained from ten specimens, representing all sample types (23%). No nonspecific amplicons were observed in any of the samples. Of twelve PCR positive urine specimens three gave full allelic profiles (25%) and two a partial profile. Phylogenetic analysis allowed for species assignment. The predominant species detected was L. interrogans (10/14 and 7/8 from UK and Lao PDR, respectively). All other species were detected in samples from only one country (Lao PDR: L. borgpetersenii [1/8]; UK: L. kirschneri [1/14], L. santarosai [1/14], L. weilii [2/14]). CONCLUSION: Typing information of pathogenic Leptospira spp. was obtained directly from a variety of clinical samples using a modified MLST assay. This assay negates the need for time consuming culture of Leptospira prior to typing and will be of use both in surveillance, as single alleles enable species determination, and outbreaks for the rapid identification of clusters. PMID- 27654038 TI - Care Transitions Measure and Readmissions. PMID- 27654040 TI - Are Upper-Body Axial Symptoms a Feature of Early Parkinson's Disease? AB - BACKGROUND: Axial disorders are considered to appear late in the course of Parkinson's disease (PD). The associated impact on quality of life (QoL) and survival and the lack of an effective treatment mean that understanding and treating axial disorders is a key challenge. However, upper-body axial disorders (namely dysarthria, swallowing and breathing disorders) have never been prospectively assessed in early-stage PD patients. OBJECTIVES: To characterize upper-body axial symptoms and QoL in consecutive patients with early-stage PD. METHODS: We prospectively enrolled 66 consecutive patients with early-stage PD (less than 3 years of disease progression) and assessed dysarthria, dysphagia and respiratory function (relative to 36 controls) using both objective and patient reported outcomes. RESULTS: The mean disease duration was 1.26 years and the mean UPDRS motor score was 19.4 out of 108. 74% of the patients presented slight dysarthria (primarily dysprosodia). Men appeared to be more severely affected (i.e. dysphonia). This dysfunction was strongly correlated with low swallowing speed (despite the absence of complaints about dysphagia), respiratory insufficiency and poor QoL. Videofluorography showed that oral-phase swallowing disorders affected 60% of the 31 tested patients and that pharyngeal-phase disorders affected 21%. 24% of the patients reported occasional dyspnea, which was correlated with anxiety in women but not in men. Marked diaphragmatic dysfunction was suspected in 42% of the patients (predominantly in men). CONCLUSION: Upper body axial symptoms were frequent in men with early-stage PD, whereas women presented worst non-motor impairments. New assessment methods are required because currently available tools do not reliably detect these upper body axial disorders. PMID- 27654041 TI - [Postresuscitation care]. AB - Witnessed collapse, bystander resuscitation and the use of automated external defibillators for defibrillatable arrhythmias, are recognized as strong predictors for a good prognosis after cardiac arrest. In addition, patient care after return of spontaneous circulation (ROSC), i.e. postresuscitation care, has been identified as an important factor for survival. It is necessary to differentiate between measures for treating the underlying cause of the cardiac arrest and measures for limiting reperfusion injury after global hypoxia and ischemia. The importance of urgent coronary angiography in cases of ST-elevation myocardial infarction (STEMI) and for patients with suspected cardiac origin without STEMI, especially with hemodynamic instability is emphasized in the current European Resuscitation Council (ERC) guidelines. In order to minimize reperfusion injury targeted temperature management (32-36 degrees C) is advised, rewarming must be controlled and fever and hyperthermia avoided. The mean arterial pressure should be adjusted to allow sufficient urine production (1 ml/kg/h) and blood glucose should be <=10 mmol/l (<=180 mg/dl). Analgosedation is necessary in most patients, especially with the use of targeted temperature management. Convulsive seizures must be consistently treated. Cardiac arrest centers provide a treatment strategy for postresuscitation care involving emergency percutaneous coronary angiography, targeted temperature management and comprehensive neurological evaluation for estimating the prognosis. Whether establishing these centers will actually lead to improved survival still needs to be proven. PMID- 27654042 TI - Soft-Tissue Reconstruction Without Fibular Reconstruction in Traumatic Injuries of the Ankle With Fibular Loss. PMID- 27654043 TI - Endoscopy-Assisted Achilles Tendon Reconstruction With a Central Turndown Flap and Semitendinosus Augmentation. AB - BACKGROUND: The objective of this study was to report the results of a new minimally invasive Achilles reconstruction technique and to assess the perioperative morbidity, medium- to long-term outcomes, and functional results. METHODS: Our series was comprised 14 patients (11 men and 3 women), with a mean age of 45.6 years at surgery. Each patient had a chronic Achilles tendon rupture. The mean interval from rupture to surgery was 5.5 months (range, 2-10). The mean total follow-up was 30.1 months (range, 12-78). All patients were operated with a central turndown flap augmented with free semitendinosus tendon graft and percutaneous sutures in a minimally invasive approach assisted by endoscopy. The patients underwent retrospective assessment by clinical examination, the American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hindfoot score, and the Achilles Tendon Total Rupture Score (ATRS). Paired t tests were used to assess the preoperative and postoperative AOFAS scores, ATRS scores, and ankle range of motion. RESULTS: The length of the defect ranged from 3 to 8 cm (mean, 5.1), while the length of the turndown flap ranged from 8 to 13 cm (mean, 10.1). The mean AOFAS score improved from 64.5 points preoperatively to 96.9 points at last follow-up. The mean ATRS score improved from 49.4 preoperatively to 91.4 points at last follow-up. None of the patients developed a wound complication. No patient had a rerupture or sural nerve damage. CONCLUSION: All patients in our study had a favorable outcome with no complications. We believe that with this triple-repair technique, one can achieve a strong and robust repair such as in open surgery while at the same time reducing the incidence of complications. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 27654044 TI - Percutaneous Method to Determine Optimal Surgical Approach for Delayed Treatment of Calcaneus Fracture. PMID- 27654045 TI - Development of an Expectations Survey for Patients Undergoing Foot and Ankle Surgery. AB - BACKGROUND: Many authors have reported on patient satisfaction from foot and ankle surgery, but rarely on expectations, which may vary widely between patients and strongly affect satisfaction. In this study, we aimed to develop a patient derived survey on expectations from foot and ankle surgery. METHODS: We developed and tested our survey using a 3-phase process. Patients with a wide spectrum of foot and ankle diagnoses were enrolled. In phase 1, patients were interviewed preoperatively with open-ended questions about their expectations from surgery. Major concepts were grouped into categories that were used to form a draft survey. In phase 2, the survey was administered to preoperative patients on 2 occasions to establish test-retest reliability. In phase 3, the final survey items were selected based on weighted kappa values for response concordance and clinical relevance. RESULTS: In phase 1, 94 preoperative patients volunteered 655 expectations. Twenty-nine representative categories were discerned by qualitative analysis and became the draft survey. In phase 2, another 60 patients completed the draft survey twice preoperatively. In phase 3, 23 items were retained for the final survey. For retained items, the average weighted kappa value was 0.54. An overall score was calculated based on the amount of improvement expected for each item on the survey and ranged from zero to 100, with higher scores indicating more expectations. For patients in phase 2, mean scores for both administrations were 65 and 66 and approximated normal distributions. The intraclass correlation coefficient between scores was 0.78. CONCLUSION: We developed a patient-derived survey specific to foot and ankle surgery that is valid, reliable, applicable to diverse diagnoses, and includes physical and psychological expectations. The survey generates an overall score that is easy to calculate and interpret, and thus offers a practical and comprehensive way to record patients' expectations. We believe this survey may be used preoperatively by surgeons to help guide patients' expectations and facilitate shared decision making. LEVEL OF EVIDENCE: Level II, cross-sectional study. PMID- 27654046 TI - Three-Dimensional Analysis of Fibular Motion After Fixation of Syndesmotic Injuries With a Screw or Suture-Button Construct. AB - BACKGROUND: Suture-button constructs are an alternative to screw fixation for syndesmotic injuries, and proponents advocate that suture-button constructs may allow physiological motion of the syndesmosis. Recent biomechanical data suggest that fibular instability with syndesmotic injuries is greatest in the sagittal plane, but the design of a suture-button construct, being a rope and 2 retention washers, is most effective along the axis of the rope (in the coronal plane). Some studies report that suture-button constructs are able to constrain fibular motion in the coronal plane, but the ability of a tightrope to constrain sagittal fibular motion is unknown. The purpose of this study was to assess fibular motion in response to an external rotation stress test in a syndesmotic injury model after fixation with a screw or suture-button constructs. METHODS: Eleven fresh frozen cadaver whole legs with intact tibia-fibula articulations were secured to a custom fixture. Fibular motion (coronal, sagittal, and rotational planes) in response to a 6.5-Nm external rotation moment applied to the foot was recorded with fluoroscopy and a high-resolution motion capture system. Measures were taken for the following syndesmotic conditions: intact, complete lateral injury, complete lateral and deltoid injury, repair with a tetracortical 4.0-mm screw, and repair with a suture button construct (Tightrope; Arthrex, Naples, FL) aimed from the lateral fibula to the anterior medial malleolus. RESULTS: The suture button construct allowed significantly more sagittal plane motion than the syndesmotic screw. Measurements acquired with mortise imaging did not detect differences between the intact, lateral injury, and 2 repair conditions. External rotation of the fibula was significantly increased in both injury conditions and was not restored to intact levels with the screw or the suture-button construct. CONCLUSION: A single suture-button placed from the lateral fibula to the anterior medial malleolus was unable to replicate the motion observed in the intact specimen when subjected to an external rotation stress test and allowed significantly more posterior motion of the fibula than when fixed with a screw in simulated highly unstable injuries. CLINICAL RELEVANCE: Fixation of a syndesmotic injury with a single suture-button construct did not restore physiological fibular motion, which may have implications for postoperative care and clinical outcomes. PMID- 27654049 TI - Adult emergency medicine at a glance Thomas Hughes and Jaycen Cruickshank Adult emergency medicine at a glance Wiley-Blackwell L21.99 120pp 9781405189019 1405189010 [Formula: see text]. AB - AN IDEAL text for junior doctors, nurses or students of any discipline who work in emergency departments (eds), this book encapsulates complex subject areas into easily digestible, bite-sized pieces that would not overwhelm even the most anxious learner. PMID- 27654047 TI - Geographic distribution of amino acid mutations in DHFR and DHPS in Plasmodium vivax isolates from Lao PDR, India and Colombia. AB - BACKGROUND: Non-synonymous mutations in dhfr and dhps genes in Plasmodium vivax are associated with sulfadoxine-pyrimethamine (SP) resistance. The present study aimed to assess the prevalence of point mutations in P. vivax dhfr (pvdhfr) and P. vivax dhps (pvdhps) genes in three countries: Lao PDR, India and Colombia. METHODS: Samples from 203 microscopically diagnosed vivax malaria were collected from the three countries. Five codons at positions 13, 57, 58, 61, and 117 of pvdhfr and two codons at positions 383 and 553 of pvdhps were examined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The largest number of 58R/117 N double mutations in pvdhfr was observed in Colombia (94.3 %), while the corresponding wild-type amino acids were found at high frequencies in Lao PDR during 2001-2004 (57.8 %). Size polymorphism analysis of the tandem repeats within pvdhfr revealed that 74.3 % of all the isolates carried the type B variant. Eighty-nine per cent of all the isolates examined carried wild-type pvdhps A383 and A553. CONCLUSIONS: Although SP is not generally used to treat P. vivax infections, mutations in dhfr and dhps that confer antifolate resistance in P. vivax are common. The data strongly suggest that, when used primarily to treat falciparum malaria, SP can exert a substantial selective pressure on P. vivax populations, and this can lead to point mutations in dhfr and dhps. Accurate data on the global geographic distribution of dhfr and dhps genotypes should help to inform anti-malarial drug-use policies. PMID- 27654050 TI - 500 tips for communicating with the public Maggie Kindred 500 tips for communicating with the public and Michael Kindred Jessica Kingsley L14.99 160pp 9781849051750 1849051755 [Formula: see text]. AB - LogicaLLy structured and divided into well-organised sections on topics such as listening, giving advice and setting a tone, this book covers all the issues nurses may encounter when communicating with people. PMID- 27654051 TI - The ECG Workbook Angela Rowlands The ECG Workbook and Andrew Sargent M&K Publishing L25 108pp 9781905539772 1905539770 [Formula: see text]. AB - THIS IS the second edition of an informative guide for several tasks associated with electrocardiography, from attaching electrodes to patients to interpreting the results of 12-lead electrocardiograms (ecgs). PMID- 27654052 TI - Complete mental health: the go-to guide for clinicians and patients John Ingram Walker Complete mental health: the go-to guide for clinicians and patients WW Norton and Company L19.99 338pp 9780393706239 0393706230 [Formula: see text]. AB - PRESENTED IN a witty and engaging style, this book is a primer for doctors and non-medical practitioners whose areas of expertise lie primarily outside the management of mental health disorders but who are presented regularly with clients with mental health issues. PMID- 27654053 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27654048 TI - Fusion Molecules of Heat Shock Protein HSPX with Other Antigens of Mycobacterium tuberculosis Show High Potential in Serodiagnosis of Tuberculosis. AB - Variable individual response against the antigens of Mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. Fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. Antigens of M. tuberculosis HSPX and PE35 were expressed in a soluble form whereas tnPstS1 and FbpC1 were expressed as inclusion bodies at 37 degrees C. Heat shock protein HSPX when attached to the N-termini of the antigens PE35, tnPstS1 and FbpC1, all the fusion molecules were expressed at high levels in E. coli in a soluble form. ELISA analysis of the plasma samples of TB patients against HSPX-tnPstS1 showed 57.7% sensitivity which is nearly the same as the expected combined value obtained after deducting the number of plasma samples (32) containing the antibodies against both the individual antigens. Likewise, the 54.4% sensitivity of HSPX-PE35 was nearly the same as that expected from the combined values of the contributing antigens. Structural analysis of all the fusion molecules by CD spectroscopy showed that alpha-helical and beta-sheet contents were found close to those obtained through molecular modeling. Molecular modeling studies of HSPX-tnPstS1 and HSPX-PE35 support the analytical results as most of the epitopes of the contributing antigens were found to be available for binding to the corresponding antibodies. Using these fusion molecules in combination with other antigenic molecules should reduce the number of antigenic proteins required for a more reliable and economical serodiagnosis of tuberculosis. Also, HSPX seems to have potential application in soluble expression of heterologous proteins in E. coli. PMID- 27654056 TI - Forgetting dementia? AB - It is increasingly understood that care for older adults with cognitive impairment who attend EDs should be improved. PMID- 27654054 TI - Diary. AB - Our roundup of what's on. PMID- 27654055 TI - Ultrasound and fractures. AB - Ultrasound use by nurse practitioners may have a place in nurse-led minor injury units or community hospital EDs that have no continuous radiography services, or at triage in larger departments. PMID- 27654057 TI - Frequent attenders. AB - In most emergency departments (EDs), a few patients account for a considerable number of attendances and hospital admissions. Newton and colleagues describe how to reduce these numbers by introducing individual care plans. PMID- 27654058 TI - Physical fitness and resuscitation. AB - Would a muscle-strength exercise programme for ED staff improve patient survival rates after cardiac arrest? Ock and colleagues from the Catholic University of Korea think that it could. They studied the physical fitness of 47 medical students, 25 men and 22 women with a mean age of 22 years, by assessing their ability to perform uninterrupted chest compressions on a manikin for five minutes. PMID- 27654059 TI - Optimum treatment for mediastinal lymph node positive (N2) resectable non-small cell lung cancer: what is the role for surgery? AB - INTRODUCTION: A third of patients with Non-Small Cell Lung Cancer (NSCLC) present with Stage III disease with mediastinal (N2) nodal involvement representing an extremely heterogeneous population with a generally poor prognosis. Areas covered: This article describes the complexity of Stage III-N2 patients reviewing the outcomes of key clinical trials while highlighting the trial designs and subtleties that have created controversy in management. Both bimodality approaches combining chemotherapy with either surgery or radiation and trimodality approaches combining chemotherapy with both local therapies are reviewed. Finally, prognostic factors and future directions are explored for the management of this population. Expert commentary: Upfront surgery is not recommended for patients with Stage III-N2 NSCLC. Neoadjuvant approaches with both chemotherapy and chemoradiation are acceptable in a multidisciplinary setting if appropriate surgery is performed by a dedicated thoracic surgeon. Non operative candidates should receive definitive concurrent chemoradiation. Innovative approaches are necessary to improve outcomes in this population. PMID- 27654060 TI - Precise Targeting of Liver Tumor Using Glycol Chitosan Nanoparticles: Mechanisms, Key Factors, and Their Implications. AB - Herein, we elucidated the mechanisms and key factors for the tumor-targeting ability of nanoparticles that presented high targeting efficiency for liver tumor. We used several different nanoparticles with sizes of 200-300 nm, including liposome nanoparticles (LNPs), polystyrene nanoparticles (PNPs) and glycol chitosan-5beta-cholanic acid nanoparticles (CNPs). Their sizes are suitable for the enhanced permeation and retention (EPR) effect in literature. Different in vitro characteristics, such as the particle structure, stability, and bioinertness, were carefully analyzed with and without serum proteins. Also, pH-dependent tumor cell uptakes of nanoparticles were studied using fluorescence microscopy. Importantly, CNPs had sufficient stability and bioinertness to maintain their nanoparticle structure in the bloodstream, and they also presented prolonged circulation time in the body (blood circulation half-life T1/2 = about 12.2 h), compared to the control nanoparticles. Finally, employing liver tumor bearing mice, we also observed that CNPs had excellent liver tumor targeting ability in vivo, while LNPs and PNPs demonstrated lower tumor-targeting efficiency due to the nonspecific accumulation in normal liver tissue. Liver tumor models were produced by laparotomy and direct injection of HT29 tumor cells into the left lobe of the liver of athymic nude mice. This study provides valuable information concerning the key factors for the tumor-targeting ability of nanoparticles such as stability, bioinertness, and rapid cellular uptake at targeted tumor tissues. PMID- 27654061 TI - Neural Mechanisms of Harm-Avoidance Learning: A Model for Obsessive-Compulsive Disorder? PMID- 27654062 TI - Circulating free fatty acids inhibit food intake in an oleate-specific manner in rats. AB - Previous rodent studies showed that when injected into the brain, free fatty acids (FFAs) reduced food intake in an oleate-specific manner. The present study was performed to test whether food intake is regulated by circulating FFAs in an oleate-specific manner. Male Wistar rats received an intravenous infusion of olive, safflower, or coconut oil (100mg/h), together with heparin, to raise circulating oleate, linoleate, or palmitate, respectively, and their effects on overnight food intake were evaluated. Compared to other oils, olive oil infusion showed a significantly greater effect to reduce food intake (P<0.01). Total caloric intake, the sum of the calories from the diet and infused oil, was significantly reduced with olive oil (P<0.01) but not with coconut or safflower oil infusion, suggesting an oleate-specific effect on caloric intake. To further test this idea, different groups of rats received an intravenous infusion of oleate, linoleate, or octanoate (0.5mg/h). Oleate infusion decreased overnight food intake by 26% (P<0.001), but no significant effect was seen with linoleate, octanoate, or vehicle infusion (P>0.05). The effects of olive oil or oleate infusion could not be explained by changes in plasma glucose, insulin, leptin, or total FFA levels. The olive oil effect on food intake was not reduced in vagotomized rats, suggesting that oleate sensing may not involve peripheral sensors. In contrast, olive oil's effect was attenuated in high-fat-fed rats, suggesting that this effect is regulated (or impaired) under physiological (or pathological) conditions. Taken together, the present study provides evidence that circulating oleate is sensed by the brain differentially from other FFAs to control feeding in rats. PMID- 27654064 TI - Bound exciton and free exciton states in GaSe thin slab. AB - The photoluminescence (PL) and absorption experiments have been performed in GaSe slab with incident light polarized perpendicular to c-axis of sample at 10 K. An obvious energy difference of about 34 meV between exciton absorption peak and PL peak (the highest energy peak) is observed. By studying the temperature dependence of PL and absorption spectra, we attribute it to energy difference between free exciton and bound exciton states, where main exciton absorption peak comes from free exciton absorption, and PL peak is attributed to recombination of bound exciton at 10 K. This strong bound exciton effect is stable up to 50 K. Moreover, the temperature dependence of integrated PL intensity and PL lifetime reveals that a non-radiative process, with activation energy extracted as 0.5 meV, dominates PL emission. PMID- 27654063 TI - Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia. AB - OBJECTIVES: Hyperprolactinaemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 subtype receptors in the pituitary gland. Although dopamine is considered the primary factor inhibiting prolactin release, the activity of prolactin-producing lactotrophs is also regulated by the secretagogues thyrotrophin releasing hormone, vasoactive intestinal polypeptide and serotonin (5-hydroxytryptamine; 5 HT). METHODS: We describe the association between HPRL and a set of 29 SNPs from 5-HT receptor genes HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6 in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) who were treated with classical and/or atypical antipsychotic drugs. RESULTS: None of the studied autosomal markers were found to be associated with HPRL. However, a significant association was established between various HTR2C polymorphisms and HPRL. CONCLUSIONS: This study revealed an association between HPRL and X-chromosome haplotypes comprised of the rs569959 and rs17326429 polymorphisms. PMID- 27654065 TI - One material, multiple functions: graphene/Ni(OH)2 thin films applied in batteries, electrochromism and sensors. AB - Different nanocomposites between reduced graphene oxide (rGO) and Ni(OH)2 nanoparticles were synthesized through modifications in the polyol method (starting from graphene oxide (GO) dispersion in ethylene glycol and nickel acetate), processed as thin films through the liquid-liquid interfacial route, homogeneously deposited over transparent electrodes and spectroscopically, microscopically and electrochemically characterized. The thin and transparent nanocomposite films (112 to 513 nm thickness, 62.6 to 19.9% transmittance at 550 nm) consist of alpha-Ni(OH)2 nanoparticles (mean diameter of 4.9 nm) homogeneously decorating the rGO sheets. As a control sample, neat Ni(OH)2 was prepared in the same way, consisting of porous nanoparticles with diameter ranging from 30 to 80 nm. The nanocomposite thin films present multifunctionality and they were applied as electrodes to alkaline batteries, as electrochromic material and as active component to electrochemical sensor to glycerol. In all the cases the nanocomposite films presented better performances when compared to the neat Ni(OH)2 nanoparticles, showing energy and power of 43.7 W h kg-1 and 4.8 kW kg-1 (8.24 A g-1) respectively, electrochromic efficiency reaching 70 cm2 C-1 and limit of detection as low as 15.4 +/- 1.2 MUmol L-1. PMID- 27654066 TI - Microbial degradation, cytotoxicity and antibacterial activity of polyurethanes based on modified castor oil and polycaprolactone. AB - The objective of this study was to assess the effects of type of polyol and concentration of polycaprolactone (PCL) in polyurethanes (PUs) on microbial degradability, cytotoxicity, biological properties and antibacterial activity to establish whether these materials may have biomedical applications. Chemically modified and unmodified castor oil, PCL and isophorone diisocyanate in a 1:1 ratio of NCO/OH were used. PUs were characterized by stress/strain fracture tests and hardness (ASTM D 676-59). Hydrophilic character was determined by contact angle trials and morphology was evaluated by scanning electron microscopy. Degradability with Escherichia coli and Pseudomonas aeruginosa was evaluated by measuring variations in the weight of the polymers. Cytotoxicity was evaluated using the ISO 10993-5 (MTT) method with mouse embryonic fibroblasts L-929 (ATCC(r) CCL-1) in direct contact with the PUs and with NIH/3T3 cells (ATCC(r) CRL-1658) in indirect contact with the PUs. Antimicrobial activity against E. coli and P. aeruginosa was determined. PUs derived from castor oil modified (P0 and P1) have higher mechanical properties than PUs obtained from castor oil unmodified (CO). The viability of L-929 mouse fibroblasts in contact with polymers was greater than 70%. An assessment of NIH/3T3 cells in indirect contact with PUs revealed no-toxic degradation products. Finally, the antibacterial effect of the PUs decreased by 77% for E. coli and 56% for P. aeruginosa after 24 h. These results indicate that PUs synthesized with PCL have biocidal activity against Gram-negative bacteria and do not induce cytotoxic responses, indicating the potential use of these materials in the biomedical field. PMID- 27654068 TI - Integrated ZnO Nano-Electron-Emitter with Self-Modulated Parasitic Tunneling Field Effect Transistor at the Surface of the p-Si/ZnO Junction. AB - The development of high performance nano-electron-emitter arrays with well reliability still proves challenging. Here, we report a featured integrated nano electron-emitter. The vertically aligned nano-emitter consists of two segments. The top segment is an intrinsically lightly n-type doped ZnO nano-tip, while the bottom segment is a heavily p-type doped Si nano-pillar (denoted as p-Si/ZnO nano emitter). The anode voltage not only extracted the electron emission from the emitter apex but also induced the inter-band electron tunneling at the surface of the p-Si/ZnO nano-junction. The designed p-Si/ZnO emitter is equivalent to a ZnO nano-tip individually ballasted by a p-Si/ZnO diode and a parasitic tunneling field effect transistor (TFET) at the surface of the p-Si/ZnO junction. The parasitic TFET provides a channel for the supply of emitting electron, while the p-Si/ZnO diode is benefit for impeding the current overloading and prevent the emitters from a catastrophic breakdown. Well repeatable and stable field emission current were obtained from the p-Si/ZnO nano-emitters. High performance nano emitters was developed using diamond-like-carbon coated p-Si/ZnO tip array (500 * 500), i.e., 178 MUA (4.48 mA/cm2) at 75.7 MV/m. PMID- 27654067 TI - tRNA-mimicry in IRES-mediated translation and recoding. AB - Viruses maintain compact genomes that must be packaged within capsids typically less than 200 nanometers in diameter. Therefore, instead of coding for a full set of genes needed for replication, viruses have evolved remarkable strategies for co-opting the host cellular machinery. Additionally, viruses often increase the coding capacity of their own genomes by employing overlapping open reading frames (ORFs). Some overlapping viral ORFs involve recoding events that are programmed by the viral RNA. During these programmed recoding events, the ribosome is directed to translate in an alternative reading frame. Here we describe how the Dicistroviridae family of viruses utilize an internal ribosome entry site (IRES) in order to recruit ribosomes to initiate translation at a non-AUG codon. The IRES accomplishes this in part by mimicking the structure of a tRNA. Recently, we showed that the Israeli Acute Paralysis Virus (IAPV) member of the Dicistroviridae family utilizes its IRES to initiate translation in 2 different reading frames. Thus, IAPV has evolved an apparently novel recoding mechanism that reveals important insights into translation. Finally, we compare the IAPV structure to other systems that utilize tRNA mimicry in translation. PMID- 27654069 TI - Stress and temperature dependence of the avalanche dynamics during creep deformation of metallic glasses. AB - The understanding of the mesoscopic origin of plasticity in metallic glasses remains still an open issue. At the microscopic level, Shear Transformation Zones (STZ), composed by dozens of atoms, have been identified as the basic unit of the deformation process. Macroscopically, metallic glasses perform either homogeneous or inhomogeneous flow depending on the experimental conditions. However, the emergence of macroscopic behavior resulting from STZ interactions is still an open issue and is of great interest. In the current work we present an approach to analyze the different interaction mechanisms of STZ's by studying the statistics of the avalanches produced by a metallic glass during tensile creep deformation. We identified a crossover between different regimes of avalanches, and we analyzed the dependence of such crossover on the experimental conditions, namely stress and temperature. We interpret such crossover as a transition from 3D random STZ activity to localized 2D nano-shear bands. The experimental time at which the crossover takes place seems to depend on the overall strain and strain rate in the sample. PMID- 27654070 TI - Treg cells as potential cellular targets for functionalized nanoparticles in cancer therapy. AB - Treg cell-mediated immune suppression appears to represent a significant barrier to effective anticancer immune responses and their inactivation or removal is viewed as a potential therapeutic approach. Although suitable tools for selective Treg cell manipulation in man are missing, their number and function can be altered by a number of drugs and biologicals and by reprogramming tumor infiltrating antigen presenting cells. Nanoparticles offer exceptional new options in drug and gene delivery by prolonging the circulation time of their cargo, protecting it from degradation and promoting its local accumulation in cells and tissues. In tumor therapy, the use of nanoparticles is expected to overcome limitations in drug delivery and provide novel means for cell-specific functional alteration. In this perspective, we summarize strategies suitable for interference with Treg-mediated suppression, discuss the potential use of nanoparticles for this purpose and identify additional, unexplored opportunities. PMID- 27654071 TI - Fostering the exchange of real-life data across different countries to answer primary care research questions: a protocol for an UNLOCK study from the IPCRG. PMID- 27654072 TI - Risk behavior and access to HIV/AIDS prevention services in a community sample of homeless persons entering permanent supportive housing. AB - Homeless persons suffer disproportionately high rates of HIV infection, and moving into permanent supportive housing (PSH) can provide a stable base from which to access needed prevention services. However, little is known about HIV risk or prevention behavior during this critical time of transition. The current study investigated STI and HIV risk and prevention behavior and recent use of prevention and treatment services (i.e., education, testing, medication) among homeless persons preparing to move into PSH. Data come from interviews with 421 homeless adults before they moved into PSH. Thirty-seven percent of the respondents were sexually active; of those, 75.7% reported unprotected sex. Nearly two-thirds (64%) reported past year HIV testing and 40% reported testing for another STI. Fewer than one-third (31%) of respondents reported receiving posttest counseling at their last HIV test. HIV seropositivity was self-reported by 10%. Among those persons who were HIV-positive, 57.1% reported less than 100% antiretroviral (ARV) adherence. Among HIV-negative respondents, less than 1% had been prescribed preexposure prophylaxis (PrEP). Less than half (46.4%) of the sample reported any HIV prevention education in the past year. This population of homeless adults about to move into PSH report high rates of HIV risk behavior, but low rates of HIV prevention education and very little PrEP utilization. Further, low rates of ARV adherence among HIV-positive respondents indicate significant risk for HIV transmission and acquisition. Entering PSH is a period of transition for homeless persons when integrated care is critically important to ensure positive health outcomes, but these data suggest that PrEP and other HIV prevention services are poorly accessed among this population. As such, multipronged services that integrate PrEP and other HIV prevention services are needed to prevent transmission and acquisition of HIV in this high-risk, vulnerable population and ensure the health and wellbeing of PSH residents. PMID- 27654073 TI - Clinical and bacteriological analyses of bacteremia due to Corynebacterium striatum. AB - BACKGROUND: Corynebacterium striatum was recently recognized as a potential pathogen of various infectious diseases. However, the clinical entity of this microorganism has not been clearly identified. Therefore, we analyzed C. striatum isolates from blood culture and explored their clinical determinants. METHODS: We reviewed the medical records of all patients from whom C. striatum isolates were recovered from blood culture for analysis of the patients' backgrounds and clinical course including response to antimicrobial therapy and prognosis. RESULTS: During the 5-year study period (January 2010 to December 2014), 24 C. striatum strains were isolated from blood samples, and the frequency of C. striatum bacteremia increased. The majority of the strains were multidrug resistant. All of the tested strains were susceptible to only vancomycin. The age at onset of C. striatum bacteremia encompassed all adult age groups, and at least one underlying condition was documented in all patients. Thirteen of the 24 patients were cured using appropriate antibiotics (true infection group); however, 11 of the 24 patients were cured using inappropriate antibiotic therapy or no antibiotics (contamination group). Malignancy and neutropenia significantly increased the odds of true C. striatum bloodstream infection. CONCLUSIONS: The Corynebacterium species is often considered a contaminant when isolated in culture. Instead, particularly when the strain is isolated from blood, the species should be considered clinically relevant and identified to the species level; in addition, antimicrobial susceptibility testing is recommended. PMID- 27654075 TI - Introduction. AB - No abstract available for this article. PMID- 27654074 TI - Postpartum stress urinary incontinence, is it related to vaginal delivery? AB - A postpartum stress urinary incontinence is highly prevalent in Chinese women. Both pregnancy and delivery can damage muscular, fascial, and neural mechanisms of urinary continence. Elective cesarean section (CS) is not completely protective against postpartum stress urinary incontinence. PMID- 27654078 TI - Estimation of GHG Emissions from Water Reclamation Plants in Beijing. AB - A procedure for estimating Greenhouse gas (GHG) emissions from a wastewater reclamation plant in Beijing was developed based on the process chain model. GHG emissions under two typical water reclamation treatment processes, the coagulation-sedimentation-filtration traditional process and advanced biological treatment process, were examined. The total on-site GHG emissions were estimated to be 0.0056 kg/m3 and 0.6765 kg/m3 respectively, while total off-site GHG emissions were estimated to be 0.3699 kg/m3 and 0.4816 kg/m3. The overall GHG emissions were 0.3755 kg/m3 under the type 1 treatment, which is much lower than that under the type 2 of 1.1581 kg/m3. Emissions from both processes were lower than that from the tap water production. Wastewater reclamation and reuse should be promoted as it not only saves the water resources but also can reduce the GHG emissions. Energy consumption was the most significant source of GHG emissions. Biogas recovery should be employed as it can significantly reduce the GHG emissions, especially under the type 2 treatment process. Considering the wastewater treatment and reclamation process as a whole, the type 2 treatment process has advantages in reducing the GHG emissions per unit of pollutant. This paper provides scientific basis for decision making. PMID- 27654079 TI - Pyrolysis of Dried Wastewater Biosolids Can Be Energy Positive. AB - Pyrolysis is a thermal process that converts biosolids into biochar (a soil amendment), py-oil and py-gas, which can be energy sources. The objectives of this research were to determine the product yield of dried biosolids during pyrolysis and the energy requirements of pyrolysis. Bench-scale experiments revealed that temperature increases up to 500 degrees C substantially decreased the fraction of biochar and increased the fraction of py-oil. Py-gas yield increased above 500 degrees C. The energy required for pyrolysis was approximately 5-fold less than the energy required to dry biosolids (depending on biosolids moisture content), indicating that, if a utility already uses energy to dry biosolids, then pyrolysis does not require a substantial amount of energy. However, if a utility produces wet biosolids, then implementing pyrolysis may be costly because of the energy required to dry the biosolids. The energy content of py-gas and py-oil was always greater than the energy required for pyrolysis. PMID- 27654080 TI - Modeling the Economic Feasibility of Large-Scale Net-Zero Water Management: A Case Study. AB - While municipal direct potable water reuse (DPR) has been recommended for consideration by the U.S. National Research Council, it is unclear how to size new closed-loop DPR plants, termed "net-zero water (NZW) plants", to minimize cost and energy demand assuming upgradient water distribution. Based on a recent model optimizing the economics of plant scale for generalized conditions, the authors evaluated the feasibility and optimal scale of NZW plants for treatment capacity expansion in Miami-Dade County, Florida. Local data on population distribution and topography were input to compare projected costs for NZW vs the current plan. Total cost was minimized at a scale of 49 NZW plants for the service population of 671,823. Total unit cost for NZW systems, which mineralize chemical oxygen demand to below normal detection limits, is projected at ~$10.83 / 1000 gal, approximately 13% above the current plan and less than rates reported for several significant U.S. cities. PMID- 27654081 TI - A Spike Cocktail Approach to Improve Microbial Performance Monitoring for Water Reuse. AB - Water reuse, via either centralized treatment of traditional wastewater or decentralized treatment and on-site reuse, is becoming an increasingly important element of sustainable water management. Despite advances in waterborne pathogen detection methods, low and highly variable pathogen levels limit their utility for routine evaluation of health risks in water reuse systems. Therefore, there is a need to improve our understanding of the linkage between pathogens and more readily measured process indicators during treatment. This paper describes an approach for constructing spiking experiments to relate the behavior of viral, bacterial, and protozoan pathogens with relevant process indicators. General issues are reviewed, and the spiking protocol is applied as a case study example to improve microbial performance monitoring and health risk evaluation in a water reuse system. This approach provides a foundation for the development of novel approaches to improve real or near-real time performance monitoring of water recycling systems. PMID- 27654082 TI - High Permeate Recovery for Concentrate Reduction by Integrated Membrane Process in Textile Effluent. AB - The textile dyeing industry consumes a significant amount of high-quality water for processing, which stresses water resources. In recent decades, technologies have been developed to recover water from wastewater. This study describes the high recovery (greater than 92%) of reusable water from an industrial-scale hosiery dye-water recovery facility, consisting of three stages of reverse osmosis and ultrafiltration. The effluent was pre-treated before the membrane process was performed to prevent biofouling. The process performance results in the generation of a consistent water quality that is required for dyeing operations. An average feed flux of 15 l/m2h was maintained in the reverse osmosis membrane by regular chemical dosing and cleaning. The integrated membrane process achieved a permeate with a pH of 6.5 and total dissolved solids (TDS) of 160 mg/l, with no other contaminants, which is of sufficient quality for reuse in the cotton hosiery dyeing process. PMID- 27654083 TI - Potential Water Reuse for High Strength Fruit and Vegetable Processor Wastewater with an MBR. AB - High strength food processing wastewater from two processing plants was studied to determine the effectiveness of an aerobic membrane bioreactor (MBR) to reduce BOD, TSS and nutrients below municipal sewer discharge limits. The MBR comprised a 20 L lab-scale reactor combined with a flat sheet, ultrafiltration membrane module. The parameters studied included the operational flux, solids and hydraulic retention times and recirculation ratio with regards to nitrification/denitrification. The MBR system provided excellent removal efficiency at 97% COD, 99% BOD, 99.9% TSS, 90% TKN, and 60% TP for both processing plants, which eliminated the surcharges, allowing the firms to stay competitive. Effluent reuse tests showed that activated carbon proved effective in removing color from the MBR permeate, while UV treatment was able to achieve a 5 log reduction in bacteriophage. Overall, these treatment successes show the potential for water reuse in the agrifood sector. PMID- 27654084 TI - Hospital and Municipal Wastewater: Identification of Relevant Pharmaceutical Compounds. AB - The interest in the presence of pharmaceutical compounds (PhC) in the environment has increased significantly because of their potential impact on human health. Many studies have demonstrated that PhCs can be found in hospital and municipal wastewaters, mainly due to the inefficiency of the treatment plants. However, the question is how significant the hospital contribution represents in the total municipal wastewater generated. Therefore, the objective of this paper is to perform a comparison between hospital and municipal wastewaters based on literature review, serving as a base for the implementation of more efficient management policies in hospitals and municipal wastewater treatment plants. Results indicate that there are some compounds found in higher concentrations in hospital effluents than in municipal inffluent, particularly the class of antibiotics. PMID- 27654085 TI - Evaluation of an Industrial Byproduct Glycol Mixture for Denitrification. AB - In this study, the effectiveness of an industrial byproduct that contained ethylene and propylene glycols to serve as a denitrification carbon source was investigated. Use of the byproduct was compared to methanol on the basis of denitrification rate and yield. Three sequencing batch reactors (SBR) were studied; one was fed methanol, the other two were fed with low and high dosages of the byproduct separately. The low dosage reactor (GLYL) exhibited the highest denitrification rate of 11.55 mg NOx-N/g MLVSS*h and the lowest yield of 0.21 mg VSS/mg COD, while the high dosage reactor (GLYH) had the lowest denitrification rate of 8.56 mg NOx-N/g MLVSS*h and the highest yield of 0.55 mg VSS/mg COD. The results of this study showed that the industrial byproduct can be used to effect efficient nitrogen removal, but excess dosage can cause poor performance. PMID- 27654086 TI - Phosphorus Removal in Constructed Stormwater Wetland Mesocosms Amended with Water Treatment Residuals. AB - Constructed stormwater wetlands (CSWs) reduce stormwater volume and improve water quality. One quality improvement is the removal of soluble reactive phosphorus (SRP). There has been limited study on SRP fate and transport or on the mechanisms to improve SRP removal due to the difficulty in quantifying the complex, spatially heterogeneous removal processes in two-dimensional flow. The present research analyzed the ability of wetland soil (Control) and wetland soil amended with 2%, 5%, and 8% (by mass) of aluminum-based water treatment residuals (AlWTRs) to remove SRP in surface-flow vegetated CSW mesocosms. Batch adsorption experiments showed increasing SRP sorption capacity with increased AlWTR content (590-850 mg/kg soil) compared to the Control (385 mg/kg soil); however, AlWTR amended flowing mesocosms removed only 6.0-8.8 mg/kg SRP compared to 9.3 mg/kg SRP for the Control. The lack of increased SRP removal in AlWTR-amended mesocosms was attributed to flow dynamics (only 20% of the surface outflow was quantified as subsurface flow). These results suggest the extent of infiltration versus surface flow is key to soil amendments improving SRP removal in a CSW. PMID- 27654087 TI - Nanodomains in Biomembranes with Recycling. AB - Cell membranes are out of thermodynamic equilibrium notably because of membrane recycling, i.e., active exchange of material with the cytosol. We propose an analytically tractable model of biomembrane predicting the effects of recycling on the size of protein nanodomains also called protein clusters. The model includes a short-range attraction between proteins and a weaker long-range repulsion which ensures the existence of so-called cluster phases in equilibrium, where monomeric proteins coexist with finite-size domains. Our main finding is that, when taking recycling into account, the typical cluster size at steady state increases logarithmically with the recycling rate at fixed protein concentration. Using physically realistic model parameters, the predicted 2-fold increase due to recycling in living cells is most likely experimentally measurable with the help of super-resolution microscopy. PMID- 27654088 TI - Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma. AB - OBJECTIVES: Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-gamma, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial. METHODS: The pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas. RESULTS: In squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P < 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 +/- 13.0 vs 53.3 +/- 30.5 months; P = 0.004) and disease-specific survival (226.45 +/- 11.5 vs 75.8 +/- 27.6 months; P = 0.002). CONCLUSIONS: Upregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors. PMID- 27654089 TI - The use of SBIRT in substance abuse screening. AB - There are many barriers to screening for alcohol and drug abuse. Screening, brief intervention, and referral to treatment (SBIRT) principles can be used in identifying and helping patients with substance abuse problems. This article introduces SBIRT, discusses barriers to implementation, and reviews current practice recommendations. PMID- 27654090 TI - Paternal perinatal depression: Making a case for routine screening. PMID- 27654093 TI - Assessing suicide risk in older adults. PMID- 27654091 TI - Type 1 diabetes & cardiovascular disease. PMID- 27654094 TI - Herbal supplements for health promotion and disease prevention. AB - This three-part series is designed to provide clinicians with a working knowledge of using herbal supplements for health and disease states. Common herbal preparations used for health promotion or disease prevention will be featured in this part of the series. PMID- 27654095 TI - Evaluation and treatment of the acutely injured worker. AB - The primary care NP has a significant opportunity to meet the special healthcare needs of the occupational community. While NPs routinely diagnose and treat workers, writing return-to-work restrictions can pose a challenge. PMID- 27654097 TI - Supplemental Feedings for the High-Risk Preterm Infants-Reply. PMID- 27654098 TI - Urethral Trauma After Foley Catheter Placement: A Teachable Moment. PMID- 27654099 TI - Acute stroke endovascular treatment: tips and tricks. AB - Acute ischemic stroke is a leading cause of death and disability in the United States, responsible for 1 of every 20 deaths. The efficacy of intravenous tissue plasminogen activator (tPA) alone for recanalization of large-vessel occlusion (LVO) is low. Several randomized trials have now established endovascular treatment of LVO as a standard of care. Endovascular techniques continue to evolve at a rapid pace. This review seeks to report recent advances in endovascular technology, discuss the correlation between speed of reperfusion and patient outcomes, and present mobile stroke care, shortcoming of the recent technology (such as clot fragmentation), and potential solutions to overcome these drawbacks, as well as anesthetic considerations and cost-effectiveness. PMID- 27654100 TI - Drug-eluting balloons in below the knee treatment. AB - The endovascular treatment of atherosclerotic disease of the infra-inguinal arteries has changed significantly since the introduction of drug-eluting balloon technology. The role of angioplasty using drug-eluting balloons for lesions of the superficial femoral and popliteal artery is now well established. The positive results of the use of drug-eluting balloons in the above knee segment could not be achieved in the below-the-knee segment. This paper will give an overview of the current status of drug-eluting balloon angioplasty for below-the knee lesions, and will present a review of 2 single center registry, 5 randomized trials and a meta-analysis. PMID- 27654101 TI - New tools in endovascular surgery. PMID- 27654102 TI - Total aortic endovascular repair. AB - Endovascular repair has an established role in aortic treatment and has with evolving technologies expanded its applicability to the whole aorta. Whereas open repair is still the standard treatment for aortic arch and ascending aortic pathology, in high-risk patients, endovascular treatment has gained an increasing role. Endovascular options range from hybrid procedures to total endovascular repair using chimney grafts, branched and fenestrated stent grafts. Thoracic endovascular repair (TEVAR) for descending aortic pathologies including aneurysms, traumatic aortic transection, and complicated type B aortic dissection (TBAD) have also been firmly established and in many cases shown superior to open alternatives. For uncomplicated type B aortic dissection, TEVAR is controversial weighing the benefits of the long-term outcomes with increased short-term morbidity and mortality. Endovascular thoracoabdominal aortic aneurysm repair with fenestrated and branched stent grafts have also established its role with excellent short-term results and promising long-term durability. Staging of extensive repairs is widely adopted to prevent spinal cord ischemia. Off-the shelf (OTS) devices have a complimentary role in emergency situations where custom-made device (CMD) are not available. Chimney and parallel graft techniques also still have a place in emergency situations. Fenestrated stent graft is a solid treatment for pararenal aneurysms with the trend toward more complex repair that aims for durability without compromising the operative outcomes. OTS fenestrated repair for juxtarenal aneurysms have shown its feasibility in the short-term but long-term results are yet to be published. Techniques for infrarenal aneurysm repair have reached a plateau. New devices have been developed to overcome the anatomical limitations of current stent grafts, especially for unfavorable neck anatomy. New polymer-based endovascular sealing (EVAS) technique has shown its feasibility and promising early outcomes, however long-term evidence is needed to define its role in the treatment armamentarium. Lastly, hypogastric artery preservation is now more feasible when iliac-branched devices have shown a good long-term patency and some new devices are available in clinical trial. This article gives an overview of available options and the results of endovascular solutions for the entire aorta from the ascending aorta to the iliac artery. PMID- 27654104 TI - Cu(OAc)2-Mediated Reaction of [60]Fullerene with Aldehydes and Primary Amines for the Synthesis of Fulleropyrrolines. AB - The facile one-step reaction of [60]fullerene with aldehydes and primary amines in the presence of cheap and easily available Cu(OAc)2.H2O afforded a series of new types of fulleropyrrolines with trisubstituted C?C bonds in good to excellent yields, which would be difficult to prepare by known methods. The formed fulleropyrroline under the assistance of Pd(OAc)2 and CuCl2.2H2O could be further converted to 1-fulleropyrrolidine by the chlorohydroxylation reaction of C?C bond. Subsequent elimination reaction of 1-fulleropyrrolidine with the aid of TsOH.H2O generated the scarce 1-fulleropyrroline derivative. PMID- 27654105 TI - Extent of Extrathyroidal Extension as a Significant Predictor of Nodal Metastasis and Extranodal Extension in Patients with Papillary Thyroid Carcinoma. AB - BACKGROUND: Extrathyroidal extension (ETE) and extranodal extension (ENE) indicate poor prognosis for patients with papillary thyroid carcinoma (PTC). The relationships among ETE, ENE, and nodal metastasis (N1) have not been thoroughly studied. In this study, we examined the relationships among the extent of ETE, N1, ENE, and posttreatment recurrence in patients with PTC. METHODS: This study enrolled 1693 consecutive patients with previously untreated PTC who underwent thyroidectomy between 2006 and 2009. The extent of ETE was graded based on intraoperative and pathological findings, and central and lateral neck (N1b) nodal metastases and ENE were pathologically determined. Univariate and multivariate analyses were used to identify the association of clinicopathological factors with recurrence-free survival (RFS) and to define the relationships among the extent of ETE, N1, and ENE. RESULTS: Of 1693 patients, 1087 (64.2 %) had ETE and 201 (11.9 %) had ENE. Pathologically positive lymph nodes were found in 783 patients (46.2 %), of whom 236 (30.1 %) had N1b. During the median follow-up of 86 months, 90 (5.3 %) patients had recurrences. Multivariate analyses showed that multifocality, ETE, T and N classification, the risk of structural recurrence proposed by the American Thyroid Association, and ENE were independent variables for RFS (P < .05). Patients with macroscopic ETE had a 13-fold increased risk of recurrence, and ETE had significant relationships with N1, N1b, and ENE (all P < .001). CONCLUSIONS: Local extension, nodal involvement, and ENE contribute to posttreatment recurrence of PTC. Macroscopic ETE predicts nodal metastasis and ENE, which are adverse pathologic features. PMID- 27654103 TI - Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families. AB - RATIONALE: Maternal depression and prenatal and early life stress may influence childhood wheezing illnesses, potentially through effects on immune development. OBJECTIVES: To test the hypothesis that maternal stress and/or depression during pregnancy and early life are associated with recurrent wheezing and aeroallergen sensitivity and altered cytokine responses (enhanced type 2 or reduced virus induced cytokine responses) from stimulated peripheral blood mononuclear cells at age 3 years. METHODS: URECA (Urban Environment and Childhood Asthma) is a birth cohort at high risk for asthma (n = 560) in four inner cities. Maternal stress, depression, and childhood wheezing episodes were assessed by quarterly questionnaires beginning at birth. Logistic and linear regression techniques were used to examine the relation of maternal stress/depression to recurrent wheezing and peripheral blood mononuclear cell cytokine responses at age 3 years. MEASUREMENTS AND MAIN RESULTS: Overall, 166 (36%) children had recurrent wheeze at age 3 years. Measures of maternal perceived stress at Years 2 and 3 were positively associated with recurrent wheeze (P < 0.05). Maternal depression (any year) was significantly associated with recurrent wheezing (P <= 0.01). These associations were also significant when considered in a longitudinal analysis of cumulative stress and depression (P <= 0.02). Neither stress nor depression was significantly related to aeroallergen sensitization or antiviral responses. Contrary to our original hypothesis, prenatal and Year 1 stress and depression had significant inverse associations with several type 2 cytokine responses. CONCLUSIONS: In urban children at high risk for asthma, maternal perceived stress and depression were significantly associated with recurrent wheezing but not increased atopy or reduced antiviral responses. PMID- 27654106 TI - Prognosis of Fibrosarcoma in Patients With and Without a History of Radiation for Nasopharyngeal Carcinoma. AB - PURPOSE: To determine whether radiation-induced fibrosarcoma (RIF) in patients with a history of radiotherapy for nasopharyngeal carcinoma (NPC) was associated with an inferior prognosis compared to sporadic fibrosarcoma of the head and neck. METHODS: Forty-two patients with RIF who previously received radiotherapy for NPC and 124 patients with sporadic fibrosarcoma of the head and neck were identified between January 1965 and December 2013 at our institution. Information on clinicopathologic characteristics and treatment was abstracted from medical records. The primary end point was disease-specific survival (DSS). RESULTS: The median latency from NPC diagnosis to RIF diagnosis was 9.9 years (range 3.1-36.8 years). RIF was diagnosed at an older age than sporadic fibrosarcoma. Treatment modality was significantly different between the two groups, with only 64.3 % of the RIF group receiving surgery +/- adjuvant treatment versus 91.1 % in the sporadic fibrosarcoma group (P < 0.001). Patients with RIF had poorer 5-year DSS compared to the sporadic fibrosarcoma group (36.2 vs. 50.4 %; P = 0.026). Multivariate analysis of the combined group indicated that patient group (P = 0.032), tumor, node, metastasis classification system stage (P = 0.019), histologic grade (P = 0.046) and treatment modality (P < 0.001) were independent variables affecting DSS. CONCLUSIONS: Compared to patients with sporadic fibrosarcoma, NPC survivors who develop RIF are older at diagnosis of fibrosarcoma and have an inferior prognosis. PMID- 27654107 TI - Is Radiotherapy Warranted Following Intrahepatic Cholangiocarcinoma Resection? The Impact of Surgical Margins and Lymph Node Status on Survival. AB - BACKGROUND: The role of radiotherapy (RT) for surgically resected intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Radiotherapy is often considered when positive resection margins exist. The present study sought to examine the impact of radiotherapy following ICC resection. METHODS: Patients with early stage disease, who underwent surgical resection, were identified from the National Cancer Database (1998-2013). Patients were stratified by the receipt of RT. Survival outcomes were examined following propensity score matching (PS), and a Cox regression for survival analysis was used to examine predictors of survival. RESULTS: A total of 2897 patients were identified. R0 status was achieved in 1951 patients (67.3 %). RT was delivered to 525 patients (R0 = 255, R1/R2 = 230, unknown = 43). Following PS matching, the overall survival for R0 versus R1/R2 resection was 31.2 versus 19.5 months (p < .001), respectively. RT was associated with a trend toward improved survival for R1/R2 lymph node negative patients (39.5 vs. 21.1 months; p = .052). In a multivariate model accounting for different patient and disease characteristics, RT was not associated with survival. In contrast, age, comorbidities, tumor grade, resection margins, lymph nodes status, and tumor's T stage were identified as negative predictors of survival. CONCLUSIONS: Patients with negative resection margins demonstrated improved survival outcome among ICC patients. In patients with positive resection margins and node negative disease, radiotherapy did not provide a survival benefit. Further studies are warranted to confirm and further define these results. PMID- 27654108 TI - Impact of an In-visit Decision Aid on Patient Knowledge about Contralateral Prophylactic Mastectomy: A Pilot Study. AB - BACKGROUND: Studies have reported that breast cancer patients have limited understanding about the oncologic outcomes following contralateral prophylactic mastectomy (CPM). We hypothesized that an in-visit decision aid (DA) would be associated with higher patient knowledge about the anticipated short and long term outcomes of CPM. METHODS: We piloted a DA which used the SCOPED: (Situation, Choices, Objectives, People, Evaluation and Decision) framework. Knowledge, dichotomized as "low" (<=3 correct) versus "high" (>=4 correct), was assessed immediately after the visit by a 5 item survey. There were 97 DA patients (response rate 62.2 %) and 114 usual care (UC) patients (response rate 71.3 %). RESULTS: Patient demographic factors were similar between the two groups. Twenty one (21.7 %) patients in the DA group underwent CPM compared with 18 (15.8 %) in the UC group (p = 0.22). Mean and median knowledge levels were significantly higher in the DA group compared with the UC group for patients of all ages, tumor stage, race, family history, anxiety levels, worry about CBC, and surgery type. Eighty-six (78.9 %) of UC versus 35 (37.9 %) DA patients had low knowledge. Of patients who underwent CPM, 15 (83.3 %) in the UC cohort versus 5 (25.0 %) of DA patients had "low" knowledge. CONCLUSIONS: Knowledge was higher in the DA group. The UC group had approximately three times the number of patients of the DA group who were at risk for making a poorly informed decision to have CPM. Future studies should assess the impact of increased knowledge on overall CPM rates. PMID- 27654109 TI - Shear-Wave Elastography for Papillary Thyroid Carcinoma can Improve Prediction of Cervical Lymph Node Metastasis. AB - BACKGROUND: This study aimed to investigate whether the elasticity index of shear wave elastography (SWE) can predict cervical lymph node (LN) metastasis of papillary thyroid carcinoma (PTC). METHODS: This retrospective study included 363 patients with a surgical diagnosis of PTC who underwent preoperative SWE evaluation. The elasticity indices of PTC (E mean, E max, E min, E ratio-p, and E ratio-m) and gray-scale ultrasound (US) parameters (extrathyroidal extension, multifocality, and cervical LN metastasis) were correlated with the pathologic staging parameters. The optimal cutoff values for the elasticity indices were determined for the prediction of cervical LN metastasis, and diagnostic performance was compared between gray-scale US and the combined application of gray-scale US and SWE. RESULTS: The findings showed E mean and E max to be associated with central LN metastasis (P = 0.037) and E min to be associated with lateral LN metastasis (P = 0.015). An E mean value higher than 124 kPa or an E max value higher than 138 kPa with suspicious gray-scale US findings improved the sensitivity and area under the curve (AUC) for predicting central LN metastasis (sensitivity, 45.4 and 44.6 % vs. 28 %, P < 0.001; AUC, 0.659 and 0.667 vs. 0.615, P = 0.011 and 0.019), whereas an E min value higher than 63 kPa with suspicious gray-scale US findings improved the sensitivity and AUC for predicting lateral LN metastasis (sensitivity, 95.8 vs. 75 %, P = 0.025; AUC, 0.924 vs. 0.871, P = 0.047). CONCLUSION: The quantitative elasticity index of PTC on preoperative SWE could be useful for predicting cervical LN metastasis. PMID- 27654110 TI - Outcomes After Mastectomy and Lumpectomy in Elderly Patients with Early-Stage Breast Cancer. AB - INTRODUCTION: Survival in elderly patients undergoing mastectomy or lumpectomy has not been specifically analyzed. METHODS: Patients older than 70 years of age with clinical stage I invasive breast cancer, undergoing mastectomy or lumpectomy with or without radiation, and surveyed within 3 years of their diagnosis, were identified from the Surveillance, Epidemiology, and End Results and medicare health outcomes survey-linked dataset. The primary endpoint was breast cancer specific survival (CSS). RESULTS: Of 1784 patients, 596 (33.4 %) underwent mastectomy, 918 (51.4 %) underwent lumpectomy with radiation, and 270 (15.1 %) underwent lumpectomy alone. Significant differences were noted in age, tumor size, American Joint Committee on Cancer (AJCC) stage, lymph node status (all p < 0.0001) and number of positive lymph nodes between the three groups (p = 0.003). On univariate analysis, CSS for patients undergoing lumpectomy with radiation [hazard ratio (HR) 0.61, 95 % confidence interval (CI) 0.43-0.85; p = 0.004] was superior to mastectomy. Older age (HR 1.3, 95 % CI 1.09-1.45; p = 0.002), two or more comorbidities (HR 1.57, 95 % CI 1.08-2.26; p = 0.02), inability to perform more than two activities of daily living (HR 1.61, 95 % CI 1.06-2.44; p = 0.03), larger tumor size (HR 2.36, 95 % CI 1.85-3.02; p < 0.0001), and positive lymph nodes (HR 2.83, 95 % CI 1.98-4.04; p < 0.0001) were associated with worse CSS. On multivariate analysis, larger tumor size (HR 1.89, 95 % CI 1.37-2.57; p < 0.0001) and positive lymph node status (HR 1.99, 95 % CI 1.36-2.9; p = 0.0004) independently predicted worse survival. CONCLUSIONS: Elderly patients with early stage invasive breast cancer undergoing breast conservation have better CSS than those undergoing mastectomy. After adjusting for comorbidities and functional status, survival is dependent on tumor-specific variables. Determination of lymph node status remains important in staging elderly breast cancer patients. PMID- 27654111 TI - Routine Level 2b Dissection may be Recommended Only in N1b Papillary Thyroid Carcinoma with Three- or Four-Level Lateral Lymph Node Metastasis. AB - BACKGROUND: Due to the low incidence of level 2b metastasis and the risk of spinal accessory nerve injury, previous studies have argued against routine level 2b dissection for N1b papillary thyroid carcinoma (PTC). However, other studies have suggested the importance of including level 2b during lateral neck dissection. Therefore, this study aimed to determine the necessity of routine level 2b dissection. METHODS: The study retrospectively reviewed 327 N1b PTC patients who underwent unilateral modified radical neck dissection between January 1997 and May 2016. RESULTS: The incidence of level 2b metastasis was 10.4 %, compared with 53.5 % for level 2a metastasis. The univariate analysis showed that large tumor size (p = 0.027) and simultaneous lateral lymph node metastasis (LLNM) (p = 0.002) were significantly associated with level 2b metastasis. The multivariate analysis showed that three-level (adjusted odds ratio [OR] 6.032; p = 0.020) and four-level (adjusted OR 9.398; p = 0.012) simultaneous LLNM were independent predictors for level 2b metastasis. CONCLUSIONS: Due to the low incidence of level 2b metastasis, routine level 2b dissection may not be necessary for N1b PTC patients. Level 2b dissection may be reserved for patients with more than three-level simultaneous LLNM or clinical/radiological evidence of level 2b metastasis. PMID- 27654112 TI - Utilization of Diurnal Rodents in the Research of Depression. AB - Preclinical Research Most neuropsychiatric research, including that related to the circadian system, is performed using nocturnal animals, mainly laboratory mice and rats. Mood disorders are known to be associated with circadian rhythm abnormalities, but the mechanisms by which circadian rhythm disruptions interact with depression remain unclear. As the circadian system of diurnal and nocturnal mammals differs, we previously suggested that the utilization of diurnal animal models may be advantageous for understanding these relations. During the last 10 years, we and others established the validity of several diurnal rodent species as a model for the interactions between circadian rhythms and depression. Diurnal rodents respond to photoperiod manipulation in a similar way to humans, the behavioral outcome is directly related to the circadian system, and treatment that is effective in patients is also effective in the model. Moreover, less effective treatments in patients are also less effective in the model. We, therefore, suggest that using diurnal animal models to study circadian rhythms related affective disorders, such as depression, will provide new insights that will hopefully lead to the development of more effective treatments. Drug Dev Res 77 : 347-356, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27654113 TI - Supramolecule-Inspired Fabrication of Carbon Nanoparticles In Situ Anchored Graphene Nanosheets Material for High-Performance Supercapacitors. AB - The remarkable electrochemical performance of graphene-based materials has drawn a tremendous amount of attention for their application in supercapacitors. Inspired by supramolecular chemistry, the supramolecular hydrogel is prepared by linking beta-cyclodextrin to graphene oxide (GO). The carbon nanoparticles anchored graphene nanosheets are then assembled after the hydrothermal reduction and carbonization of the supramolecular hydrogels; here, the beta-cyclodextrin is carbonized to carbon nanoparticles that are uniformly anchored on the graphene nanosheets. Transmission electron microscopy reveals that carbon nanoparticles with several nanometers are uniformly anchored on both sides of graphene nanosheets, and X-ray diffraction spectra demonstrate that the interlayer spacing of graphene is enlarged due to the anchored nanoparticles among the graphene nanosheets. The as-prepared carbon nanoparticles-anchored graphene nanosheets material (C/r-GO-1:3) possesses a high specific capacitance (310.8 F g-1, 0.5 A g 1), superior rate capability (242.5 F g-1, 10 A g-1), and excellent cycle stability (almost 100% after 10 000 cycles, at the scan rate of 50 mV s-1). The outstanding electrochemical performance of the resulting C/r-GO-1:3 is mainly attributed to (i) the presence of the carbon nanoparticles, (ii) the enlarged interlayer spacing of the graphene sheets, and (iii) the accelerated ion transport rates toward the interior of the electrode material. The supramolecule inspired approach for the synthesis of high-performance carbon nanoparticles modified graphene sheets material is promising for future application in graphene based energy storage devices. PMID- 27654114 TI - Catalytic Use of Elemental Gallium for Carbon-Carbon Bond Formation. AB - The first catalytic use of Ga(0) in organic synthesis has been developed by using a Ag(I) cocatalyst, crownether ligation, and ultrasonic activation. Ga(I) catalyzed C-C bond formations between allyl or allenyl boronic esters and acetals, ketals, or aminals have proceeded in high yields with essentially complete regio- and chemoselectivity. NMR spectroscopic analyses have revealed novel transient Ga(I) catalytic species, formed in situ through partial oxidation of Ga(0) and B-Ga transmetalation, respectively. The possibility of asymmetric Ga(I) catalysis has been demonstrated. PMID- 27654116 TI - MR-based prognostic nomogram for prostate cancer after radical prostatectomy. AB - PURPOSE: To assess a magnetic resonance imaging (MRI)-based nomogram in the prediction of prostate cancer (PCa) biochemical recurrence (BCR) within 3 years after prostatectomy. MATERIALS AND METHODS: Between 2009 and 2013, 205 patients with biopsy-confirmed PCa had MRI before prostatectomy. BCR was defined as a PSA failure (>0.2 ng/ml) after prostatectomy. MR features (cancer location, diameter, apparent diffusion coefficients [ADCs], PI-RADS v2 score, dynamic contrast enhanced [DCE] type, and MR T-stage) were retrospectively evaluated for predicting 3-year BCR based on partial least square regression analysis. Second, imaging features were added to a popularized D'Amico and CAPRA scheme to determine imaging contribution to published nomograms. Lastly, a multivariable Cox regression analysis was employed to determine the independent risk factors of time to BCR. RESULTS: Three-year BCR rate (median follow-up of 44.9 mo) was 25.4% (52/205). The area under receiver operating characteristic (ROC) curve (Az) for MR nomogram (0.909, 95% confidence interval [CI]: 0.861-0.944) was higher than popularized D'Amico (0.793, 95% CI: 0.731-0.846, P = 0.001) and CAPRA (0.809, 95% CI: 0.748-0.860, P = 0.001). The performance of D'Amico (Az: 0.901, 95% CI: 0.852 0.938, P < 0.001) and CAPRA (Az: 0.894, 95% CI: 0.843-0.932, P = 0.004) was significantly improved by adding MR findings. Tumor ADCs (hazard ratio [HR] = 1.747; P = 0.011), PI-RADS score (HR = 4.123; P = 0.039), pathological Gleason score (HR = 3.701; P = 0.004), and surgical-T3b (HR = 6.341; P < 0.001) were independently associated with time to BCR. CONCLUSION: Multiparametric MRI, when converted into a prognostic nomogram, can predict the clinical outcome in patients with PCa after prostatectomy. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:586-596. PMID- 27654115 TI - The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets. AB - The minimum information required for a glycomics experiment (MIRAGE) project was established in 2011 to provide guidelines to aid in data reporting from all types of experiments in glycomics research including mass spectrometry (MS), liquid chromatography, glycan arrays, data handling and sample preparation. MIRAGE is a concerted effort of the wider glycomics community that considers the adaptation of reporting guidelines as an important step towards critical evaluation and dissemination of datasets as well as broadening of experimental techniques worldwide. The MIRAGE Commission published reporting guidelines for MS data and here we outline guidelines for sample preparation. The sample preparation guidelines include all aspects of sample generation, purification and modification from biological and/or synthetic carbohydrate material. The application of MIRAGE sample preparation guidelines will lead to improved recording of experimental protocols and reporting of understandable and reproducible glycomics datasets. PMID- 27654118 TI - Phenylboronic Acid-Cross-Linked Nanoparticles with Improved Stability as Dual Acid-Responsive Drug Carriers. AB - Herein, a kind of dual acid-sensitive nanoparticles based on monomethoxy poly(ethylene glycol)-imine-beta-cyclodextrin is constructed by a facile phenylboronic acid-cross-linked way. The data of dynamic light scattering and transmission electron microscope reveal the cross-linked nanoparticles have improved stability. The cross-linked nanoparticles could easily self-assemble and load the anticancer drug at neutral pH condition. However, when the drug-loaded nanoparticles are delivered to extracellular tumor sites (pH ~6.8), the surface of the nanoparticles would be amino positively charged and easily internalized by tumor cell due to the cleavage of the acid-labile benzoic-imine. Subsequently, with the acidity in subcellular compartments significantly increasing (such as the endosome pH ~5.3), the loaded drug would fast release from the endocytosis carriers due to the hydrolysis of boronate ester. These features suggest that these dual acid-sensitive cross-linked nanoparticles not only possess excellent biocompatibility but also can efficiently load and deliver anticancer drug into tumor cells to enhance the inhibition of cellular proliferation, outlining a favorable platform as drug carriers. PMID- 27654117 TI - HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus. AB - Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16-monoinfected invasive anogenital cancers from Europe, Asia, and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the nonsynonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of HPV16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1-3, except in Asia, where HPV16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accounted for less than 3% of the variance. Despite containing similar repertoires of HPV16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties). Frequencies for alleles in the HPV16 E6 T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenital cancers from Central/South America displayed higher 350G allele frequencies also within HPV16_A1-3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers. PMID- 27654119 TI - The Gestational Diabetes Management System (GooDMomS): development, feasibility and lessons learned from a patient-informed, web-based pregnancy and postpartum lifestyle intervention. AB - BACKGROUND: Gestational diabetes mellitus (GDM) contributes to the epidemic of diabetes and obesity in mothers and their offspring. The primary objective of this pilot study was to: 1) refine the GDM Management System (GooDMomS), a web based pregnancy and postpartum behavioral intervention and 2) assess the feasibility of the intervention. METHODS: In phase 1, ten semi-structured interviews were conducted with women experiencing current or recent GDM mellitus GDM to garner pilot data on the web based intervention interface, content, and to solicit recommendations from women about refinements to enhance the GooDMomS intervention site. Interviews were audiotaped, transcribed and independently reviewed to identify major themes with Atlas.ti v7.0. In phase 2, a single-arm feasibility study was conducted and 23 participants were enrolled in the GooDMomS program. Participants received web lessons, self-tracking of weight and glucose, automated feedback and access to a message board for peer support. The primary outcome was feasibility, including recruitment and retention and acceptability. Secondary outcomes included the proportion of women whose gestational weight gain (GWG) was within the Institute of Medicine (IOM) guidelines and who were able to return to their pre-pregnancy weight after delivery. RESULTS: Comments from semi structured interviews focused on: 1) usability of the on-line self-monitoring diary and tracking system, 2) access to a safe, reliable social network for peer support and 3) ability of prenatal clinicians to access the on-line diary for clinical management. Overall, 21 (91 %) completed the pregnancy phase. 15/21 (71 %) of participants were within the Institute of Medicine (IOM) guidelines for GWG. Sixteen (70 %) completed the postpartum phase. 7/16 (43 %) and 9/16 (56 %) of participants returned to their pre-pregnancy weight at 6 and 30 weeks postpartum, respectively. CONCLUSIONS: This study documents the feasibility of the GooDMomS program. The results can have implications for web technology in perinatal care and inform the current care paradigm for women with GDM. Findings are supportive of further research with recruitment of a larger sample of participants and comparison of the outcomes with the intervention and standard care. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov on May 15, 2012 under protocol no. NCT01600534 . PMID- 27654121 TI - Prospective follow-up study of artificial urinary sphincter placement preserving the bulbospongiosus muscle. AB - AIMS: Artificial urinary sphincter (AUS) AMS-800(r) is an effective treatment for male stress urinary incontinence. The aim of the study was to assess the long term effectiveness and complications of artificial urinary sphincter placement preserving the bulbospongiosus muscle. METHODS: From April 2004 to March 2014, all consecutive male patients with urinary incontinence who underwent an AUS prosthesis insertion were prospectively evaluated. Surgical technique consisted of a perineal incision for cuff placement around the bulbous urethra preserving the bulbospongiosus muscle. Cure rate was defined as no pad use. RESULTS: A total of 82 consecutive patients (median age 68 years, range: 54-78) were prospectively evaluated (median follow-up 46 months, range: 12-135). Bulbospongiosus muscles were preserved intact in all cases with no intraoperative complications. Postoperative complications were reported in 14 patients (1 urethral erosion). The overall cure rate (dry rate) was 76.8% and the median ICIQ-UI score improved from 18 (range: 8-21) to 4 (range: 0-17) (P < 0.001). Artificial urinary sphincter survival rate was 95.5% (95%CI 89.4-100%) at 24 months and 62.6% (95%CI 45.5-79.6%) at 60 months. The mechanical failure rate was 6.3% (median 46.1 months, range: 22.2-100.9) and urethral atrophy and/or inadequate compression rate was 9.5% (median 58.6 months, range: 39-101.4 months). CONCLUSIONS: Our study suggests that placement of AUS preserving the bulbospongiosus muscle is technically easy and efficient, reports excellent continence rates and lower urethral erosion rates, and could delay the onset of urethral atrophy compared to other surgical procedures used for sphincter placement. PMID- 27654120 TI - GlycA Is a Novel Biomarker of Inflammation and Subclinical Cardiovascular Disease in Psoriasis. AB - RATIONALE: GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown. OBJECTIVE: To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD. METHODS AND RESULTS: Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8+/-75.4 versus 289.4+/-60.2, P<0.0001; NIH: 415.8+/-63.2 versus 346.2+/-46, P<0.0001]) and demonstrated a dose-response with psoriasis severity. In stage 2, VI (beta=0.36, P<0.001) and coronary artery disease (beta=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7+/-92.5 versus 370.1+/-78.5, P<0.001) and VI (1.93+/-0.36 versus 1.76+/-0.19, P<0.001), whereas GlycA remained associated with VI (beta=0.56, P<0.001) post treatment. CONCLUSIONS: GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases. PMID- 27654123 TI - Electrochemical Synthesis and Catalytic Properties of Encapsulated Metal Clusters within Zeolitic Imidazolate Frameworks. AB - It is very interesting and also a big challenge to encapsulate metal clusters within microporous solids to expand their application diversity. For this target, herein, we present an electrochemical synthesis strategy for the encapsulation of noble metals (Au, Pd, Pt) within ZIF-8 cavities. In this method, metal precursors of AuCl42- , PtCl62- , and PdCl42- are introduced into ZIF-8 crystals during the concurrent crystallization of ZIF-8 at the anode. As a consequence, very small metal clusters with sizes around 1.2 nm are obtained within ZIF-8 crystals after hydrogen reduction; these clusters exhibit high thermal stability, as evident from the good maintenance of their original sizes after a high-temperature test. The catalytic properties of the encapsulated metal clusters within ZIF-8 are evaluated for CO oxidations. Because of the small pore window of ZIF-8 (0.34 nm) and the confinement effect of small pores, about 80 % of the metal clusters (fractions of 0.74, 0.77, and 0.75 for Au, Pt, and Pd in ZIF-8, respectively) retain their catalytic activity after exposure to the organosulfur poison thiophene (0.46 nm), which is in contrast to their counterparts (fractions of 0.22, 0.25, and 0.20 for Au, Pt, and Pd on the SiO2 support). The excellent performances of metal clusters encapsulated within ZIF-8 crystals give new opportunities for catalytic reactions. PMID- 27654122 TI - Molecular phylogeny and timing of diversification in Alpine Rhithrogena (Ephemeroptera: Heptageniidae). AB - BACKGROUND: Larvae of the Holarctic mayfly genus Rhithrogena Eaton, 1881 (Ephemeroptera, Heptageniidae) are a diverse and abundant member of stream and river communities and are routinely used as bio-indicators of water quality. Rhithrogena is well diversified in the European Alps, with a number of locally endemic species, and several cryptic species have been recently detected. While several informal species groups are morphologically well defined, a lack of reliable characters for species identification considerably hampers their study. Their relationships, origin, timing of speciation and mechanisms promoting their diversification in the Alps are unknown. RESULTS: Here we present a species-level phylogeny of Rhithrogena in Europe using two mitochondrial and three nuclear gene regions. To improve sampling in a genus with many cryptic species, individuals were selected for analysis according to a recent DNA-based taxonomy rather than traditional nomenclature. A coalescent-based species tree and a reconstruction based on a supermatrix approach supported five of the species groups as monophyletic. A molecular clock, mapped on the most resolved phylogeny and calibrated using published mitochondrial evolution rates for insects, suggested an origin of Alpine Rhithrogena in the Oligocene/Miocene boundary. A diversification analysis that included simulation of missing species indicated a constant speciation rate over time, rather than any pronounced periods of rapid speciation. Ancestral state reconstructions provided evidence for downstream diversification in at least two species groups. CONCLUSIONS: Our species-level analyses of five gene regions provide clearer definitions of species groups within European Rhithrogena. A constant speciation rate over time suggests that the paleoclimatic fluctuations, including the Pleistocene glaciations, did not significantly influence the tempo of diversification of Alpine species. A downstream diversification trend in the hybrida and alpestris species groups supports a previously proposed headwater origin hypothesis for aquatic insects. PMID- 27654124 TI - Global Salmonidae introductions reveal stronger ecological effects of changing intraspecific compared to interspecific diversity. AB - The introduction of organisms within the native range of wild conspecifics is a widespread phenomenon and locally modifies patterns in intraspecific diversity. However, our knowledge of the resulting ecological effects, as opposed to those caused by invasion-induced changes in interspecific diversity, is still limited. Here, we investigated the ecological effects of native and non-native invaders across levels of biological organisations and recipient organisms using the global and long history introductions of salmonids. Our meta-analysis demonstrated that the global effects of native species introductions exceeded those induced by non-native invaders. The impacts of native invaders were primarily manifested at the individual level on wild conspecifics, but remained largely unexplored on other native organisms and at the community and ecosystem levels. Overlooked and poorly appreciated, quantifying the impacts of native invaders has important implications because human-assisted introductions of domesticated organisms are ubiquitous and likely to proliferate in the future. PMID- 27654125 TI - Complete mitochondrial genomes of eleven extinct or possibly extinct bird species. AB - Natural history museum collections represent a vast source of ancient and historical DNA samples from extinct taxa that can be utilized by high-throughput sequencing tools to reveal novel genetic and phylogenetic information about them. Here, we report on the successful sequencing of complete mitochondrial genome sequences (mitogenomes) from eleven extinct bird species, using de novo assembly of short sequences derived from toepad samples of degraded DNA from museum specimens. For two species (the Passenger Pigeon Ectopistes migratorius and the South Island Piopio Turnagra capensis), whole mitogenomes were already available from recent studies, whereas for five others (the Great Auk Pinguinis impennis, the Imperial Woodpecker Campehilus imperialis, the Huia Heteralocha acutirostris, the Kauai Oo Moho braccathus and the South Island Kokako Callaeas cinereus), there were partial mitochondrial sequences available for comparison. For all seven species, we found sequence similarities of >98%. For the remaining four species (the Kamao Myadestes myadestinus, the Paradise Parrot Psephotellus pulcherrimus, the Ou Psittirostra psittacea and the Lesser Akialoa Akialoa obscura), there was no sequence information available for comparison, so we conducted blast searches and phylogenetic analyses to determine their phylogenetic positions and identify their closest extant relatives. These mitogenomes will be valuable for future analyses of avian phylogenetics and illustrate the importance of museum collections as repositories for genomics resources. PMID- 27654126 TI - Reduced field-of-view DWI with robust fat suppression and unrestricted slice coverage using tilted 2D RF excitation. AB - PURPOSE: Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) using 2D echo-planar radiofrequency (2DRF) excitation has been widely and successfully applied in clinical settings. The purpose of this work is to further improve its clinical utility by overcoming slice coverage limitations without any scan time penalty while providing robust fat suppression. THEORY AND METHODS: During multislice imaging with 2DRF pulses, periodic sidelobes in the slice direction cause partial saturation, limiting the slice coverage. In this work, a tilting of the excitation plane is proposed to push the sidelobes out of the imaging section while preserving robust fat suppression. The 2DRF pulse is designed using Shinnar Le Roux algorithm on a rotated excitation k-space. The performance of the method is validated via simulations, phantom experiments, and high in-plane resolution in vivo DWI of the spinal cord. RESULTS: Results show that rFOV DWI using the tilted 2DRF pulse provides increased signal-to-noise ratio, extended coverage, and robust fat suppression, without any scan time penalty. CONCLUSION: Using a tilted 2DRF excitation, a high-resolution rFOV DWI method with robust fat suppression and unrestricted slice coverage is presented. This method will be beneficial in clinical applications needing large slice coverage, for example, axial imaging of the spine, prostate, or breast. Magn Reson Med 76:1668-1676, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27654127 TI - Oligomerization of N-Heterocyclic Silylene into Zwitterionic Silenes. AB - N-Heterocyclic carbenes (NHC's) are known to serve as efficient substrates for the stabilization of various transient species possessing low-valent Group 14 elements and for the generation of double E=C bonds. Herein, we report that the thermal tri- and tetramerizations of pyridoannulated silylene 1 lead to the formation of remarkably stable silenes 2 and 3 featuring zwitterionic distribution of electron density. Co-oligomerization of 1 and its germanium analogue gives a related tetrameric product 4 containing low-valent germanium atom stabilized by binding with the partial carbene-character C atom. Bonding situations in 2-4 are best described as silene or germene with the significant zwitterionic distribution of electron density. The singlet diradical electronic state of 2 is 10 kcal mol-1 higher than the ground state configuration. PMID- 27654128 TI - Freedom of information: can researchers still promise control of participants' data? PMID- 27654129 TI - Patients with Metastatic Colorectal Cancer and Hyperbilirubinemia Treated with FOLFIRI plus Bevacizumab as First-Line Treatment. AB - Metastatic colorectal cancer (mCRC) combined with hyperbilirubinemia is typically considered a contraindication to irinotecan-based therapy, a proven first-line treatment of mCRC. Herein, we present 6 consecutive patients with mCRC combined with hyperbilirubinemia who underwent UGT1A1 genotyping before receiving FOLFIRI plus bevacizumab. Dose escalation of irinotecan was performed according to the results of UGT1A1 genotyping in all patients. Improvement in the serum total bilirubin level to a normal range was noted in all 6 patients. Disease control was 100%. The median progression-free survival was 7.5 months and the median overall survival was 8.5 months. FOLFIRI plus bevacizumab as a first-line chemotherapy may achieve effective disease control and be safe in patients with mCRC and hyperbilirubinemia based on UGT1A1 genotyping. More prospective clinical studies are necessary to evaluate the clinical benefits and safety of this treatment approach. PMID- 27654130 TI - Social network characteristics and resource access among formerly displaced households in Lira, Uganda. AB - In rural African communities, the support of extended family, friends, and neighbours is essential in borrowing or leveraging land, labour, food, and money, especially at times of social and financial turmoil. Little is known, though, about the nature of the networks and the conditions under which they may generate greater support in post-conflict communities. This study, conducted in the Lira district of northern Uganda, examined the composition, proximity, and size of the networks that households utilise to gain access to resources during and after resettlement. Network structures with more kin and co-resident ties were found to offer greater resource access to households in post-conflict settings. Furthermore, there was a lack of meaningful linkages outside of a person's own village, especially with regard to households whose head has no or a low level of education. These findings enhance understanding of the specific role of relationships in social support for resource access among households in post conflict communities. PMID- 27654131 TI - Oculomotor, Vestibular, and Reaction Time Tests in Mild Traumatic Brain Injury. AB - OBJECTIVE: Mild traumatic brain injury is a major public health issue and is a particular concern in sports. One of the most difficult issues with respect to mild traumatic brain injury involves the diagnosis of the disorder. Typically, diagnosis is made by a constellation of physical exam findings. However, in order to best manage mild traumatic brain injury, it is critically important to develop objective tests that substantiate the diagnosis. With objective tests the disorder can be better characterized, more accurately diagnosed, and studied more effectively. In addition, prevention and treatments can be applied where necessary. METHODS: Two cohorts each of fifty subjects with mild traumatic brain injury and one hundred controls were evaluated with a battery of oculomotor, vestibular and reaction time related tests applied to a population of individuals with mild traumatic brain injury as compared to controls. RESULTS: We demonstrated pattern differences between the two groups and showed how three of these tests yield an 89% sensitivity and 95% specificity for confirming a current diagnosis of mild traumatic brain injury. INTERPRETATION: These results help better characterize the oculomotor, vestibular, and reaction time differences between those the mild traumatic brain injury and non-affected individuals. This characterization will allow for the development of more effective point of care neurologic diagnostic techniques and allow for more targeted treatment which may allow for quicker return to normal activity. PMID- 27654132 TI - Knowledge of Kidney Donation Among Care Givers in Two Tertiary Hospitals in Southwest Nigeria. AB - One of the major challenges of kidney transplantation is shortage of kidney donors. Care givers (CGs) are potential kidney donors, but the majority of them are unwilling to donate due to inadequate knowledge on kidney donation. This study evaluated the knowledge of kidney donation and its determinants among CGs in two tertiary hospitals in Southwest Nigeria. This was a cross-sectional study that was carried out in the Kidney Care Centre (KCC), Ondo and Babcock University Teaching Hospital (BUTH), Ilishan-Remo using a self-administered pretested questionnaire that assessed knowledge of kidney donation and its determinants. Pvalue of <0.05 was taken as significant. A total of 244 respondents participated in the study. The majority were below 40 years, married, and female. The proportion of respondents with adequate knowledge of kidney donation was 63.4%. More respondents from BUTH compared to KCC had adequate knowledge of kidney donation (80% vs. 46.7%, P <= 0.001). Similarly, the mean knowledge score was higher in respondents from BUTH (P <= 0.001). Factors that determined knowledge of kidney donation were female gender (AOR: 3.43, 95% CI: 1.25-9.40, P = 0.02) and social class (AOR: 1.22, 95% CI: 0.50-2.95, P <= 0.001). There was positive correlation between knowledge of kidney donation among the respondents from both hospitals and their willingness to donate kidneys (r = 0.439, P <= 0.001). Knowledge of kidney donation was better among BUTH's respondents. Gender and social class were predictors of knowledge of kidney donation. Improving knowledge of kidney donation may improve willingness to donate among the public. PMID- 27654133 TI - Is screening for abnormal ECG patterns justified in long-term follow-up of childhood cancer survivors treated with anthracyclines? AB - BACKGROUND: ECG and echocardiography are noninvasive screening tools to detect subclinical cardiotoxicity in childhood cancer survivors (CCSs). Our aims were as follows: (1) assess the prevalence of abnormal ECG patterns, (2) determine the agreement between abnormal ECG patterns and echocardiographic abnormalities; and (3) determine whether ECG screening for subclinical cardiotoxicity in CCSs is justified. PROCEDURE: We retrospectively studied ECG and echocardiography in asymptomatic CCSs more than 5 years after anthracycline treatment. Exclusion criteria were abnormal ECG and/or echocardiogram at the start of therapy, incomplete follow-up data, clinical heart failure, cardiac medication, and congenital heart disease. ECG abnormalities were classified using the Minnesota Code. Level of agreement between ECG and echocardiography was calculated with Cohen kappa. RESULTS: We included 340 survivors with a mean follow-up of 14.5 years (range 5-32). ECG was abnormal in 73 survivors (21.5%), with ventricular conduction disorders, sinus bradycardia, and high-amplitude R waves being most common. Prolonged QTc (>0.45 msec) was found in two survivors, both with a cumulative anthracycline dose of 300 mg/m2 or higher. Echocardiography showed abnormalities in 44 survivors (12.9%), mostly mild valvular abnormalities. The level of agreement between ECG and echocardiography was low (kappa 0.09). Male survivors more often had an abnormal ECG (corrected odds ratio: 3.00, 95% confidence interval: 1.68-5.37). CONCLUSIONS: Abnormal ECG patterns were present in 21% of asymptomatic long-term CCSs. Lack of agreement between abnormal ECG patterns and echocardiographic abnormalities may suggest that ECG is valuable in long-term follow-up of CCSs. However, it is not clear whether these abnormal ECG patterns will be clinically relevant. PMID- 27654137 TI - Discriminative Scale Space Tracking. AB - Accurate scale estimation of a target is a challenging research problem in visual object tracking. Most state-of-the-art methods employ an exhaustive scale search to estimate the target size. The exhaustive search strategy is computationally expensive and struggles when encountered with large scale variations. This paper investigates the problem of accurate and robust scale estimation in a tracking-by detection framework. We propose a novel scale adaptive tracking approach by learning separate discriminative correlation filters for translation and scale estimation. The explicit scale filter is learned online using the target appearance sampled at a set of different scales. Contrary to standard approaches, our method directly learns the appearance change induced by variations in the target scale. Additionally, we investigate strategies to reduce the computational cost of our approach. Extensive experiments are performed on the OTB and the VOT2014 datasets. Compared to the standard exhaustive scale search, our approach achieves a gain of 2.5 percent in average overlap precision on the OTB dataset. Additionally, our method is computationally efficient, operating at a 50 percent higher frame rate compared to the exhaustive scale search. Our method obtains the top rank in performance by outperforming 19 state-of-the-art trackers on OTB and 37 state-of-the-art trackers on VOT2014. PMID- 27654138 TI - Clustering by Minimum Cut Hyperplanes. AB - Minimum normalised graph cuts are highly effective ways of partitioning unlabeled data, having been made popular by the success of spectral clustering. This work presents a novel method for learning hyperplane separators which minimise this graph cut objective, when data are embedded in Euclidean space. The optimisation problem associated with the proposed method can be formulated as a sequence of univariate subproblems, in which the optimal hyperplane orthogonal to a given vector is determined. These subproblems can be solved in log-linear time, by exploiting the trivial factorisation of the exponential function. Experimentation suggests that the empirical runtime of the overall algorithm is also log-linear in the number of data. Asymptotic properties of the minimum cut hyperplane, both for a finite sample, and for an increasing sample assumed to arise from an underlying probability distribution are discussed. In the finite sample case the minimum cut hyperplane converges to the maximum margin hyperplane as the scaling parameter is reduced to zero. Applying the proposed methodology, both for fixed scaling, and the large margin asymptotes, is shown to produce high quality clustering models in comparison with state-of-the-art clustering algorithms in experiments using a large collection of benchmark datasets. PMID- 27654134 TI - Seasonal variation in male alternative reproductive tactics. AB - Genetic parentage analyses reveal considerable diversity in alternative reproductive behaviours (e.g. sneaking) in many taxa. However, little is known about whether these behaviours vary seasonally and between populations. Here, we investigate seasonal variation in male reproductive behaviours in a population of two-spotted gobies (Gobiusculus flavescens) in Norway. Male two-spotted gobies guard nests, attract females and care for fertilized eggs. We collected clutches and nest-guarding males early and late in the breeding season in artificial nests and used microsatellite markers to reconstruct parentage from a subset of offspring from each nest. We hypothesized that mating, reproductive success and sneaking should be more prevalent early in the breeding season when competition for mates among males is predicted to be higher. However, parentage analyses revealed similar values of mating, reproductive success and high frequencies of successful sneaking early (30% of nests) and late (27% of nests) in the season. We also found that multiple females with eggs in the same nest were fertilized by one or more sneaker males, indicating that some males in this population engage in a satellite strategy. We contrast our results to previous work that demonstrates low levels of cuckoldry in a population in Sweden. Our results demonstrate marked stability in both the genetic mating system and male alternative reproductive tactics over the breeding season. However, sneaking rates may vary geographically within a species, likely due to local selection influencing ecological factors encountered at different locations. PMID- 27654139 TI - Saliency Detection on Light Field. AB - Existing saliency detection approaches use images as inputs and are sensitive to foreground/background similarities, complex background textures, and occlusions. We explore the problem of using light fields as input for saliency detection. Our technique is enabled by the availability of commercial plenoptic cameras that capture the light field of a scene in a single shot. We show that the unique refocusing capability of light fields provides useful focusness, depths, and objectness cues. We further develop a new saliency detection algorithm tailored for light fields. To validate our approach, we acquire a light field database of a range of indoor and outdoor scenes and generate the ground truth saliency map. Experiments show that our saliency detection scheme can robustly handle challenging scenarios such as similar foreground and background, cluttered background, complex occlusions, etc., and achieve high accuracy and robustness. PMID- 27654140 TI - Daily physical activity patterns from hip- and wrist-worn accelerometers. AB - Accelerometer wear location may influence physical activity estimates. This study investigates this relationship through the examination of activity patterns throughout the day. Participants from the aging research evaluating accelerometry (AREA) study (n men = 37, n women = 47, mean age (SD) = 78.9 (5.5) years) were asked to wear accelerometers in a free-living environment for 7 d at three different wear locations; one on each wrist and one on the right hip. During waking hours, wrist-worn accelerometers consistently produced higher median activity counts, about 5 * higher, as well as wider variability compared to hip worn monitors. However, the shape of the accrual pattern curve over the course of the day for the hip and wrist are similar; there is a spike in activity in the morning, with a prolonged tapering of activity level as the day progresses. The similar patterns of hip and wrist activity accrual provide support that each location is capable of estimating total physical activity volume. The examination of activity patterns over time may provide a more detailed way to examine differences in wear location and different subpopulations. PMID- 27654141 TI - Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort. AB - OBJECTIVE: We aimed to determine the prevalence of melanocortin-4 receptor (MC4R) variants in a large German cohort of children with obesity in a pediatric outpatient clinic and to ascertain whether there is a specific phenotype associated with loss-of-function variants as previously reported. STUDY DESIGN: Eight hundred and ninety-nine patients from our pediatric obesity clinic were screened for MC4R variants by DNA sequencing after PCR amplification. Retrospective statistical analysis of anthropometric and metabolic characteristics was performed, comparing patients with and without MC4R variants across the entire cohort (n=586) as well as in case-control analysis using patients with common sequence MC4R individually matched for age, sex and body mass index standard deviation score (SDS) (n=11 case-control pairs). RESULTS: We identified heterozygous variants within the coding region of the MC4R gene in n=22 (2.45%) patients. Fourteen (1.56%) had a variant that impaired receptor function. One new frameshift (p.F152Sfs), an yet unpublished nonsense mutation (p.Q156X) and one nonsynonymous variation (p.V65E) described in the Mouse Genome Database were detected. Across the whole cohort, at all ages, mean height SDS in subjects with impaired receptor function was higher than in patients with common sequence MC4R. In matched individuals, this trend persisted (8 of the 11 pairs) within the case-control setting. No differences were found regarding metabolic characteristics. CONCLUSIONS: The observed prevalence of mutations causing impaired receptor function in this large cohort is comparable to other pediatric cohorts. MC4R deficiency tends to lead to a taller stature, confirming previous clinical reports. The association of MC4R mutations with a distinct phenotype concerning metabolic characteristics remains questionable. PMID- 27654142 TI - Obesity and developmental delay in a patient with uniparental disomy of chromosome 2. AB - OBJECTIVE: Uniparental disomy (UPD) is an unusual situation wherein two homologous chromosomes are inherited from the same parent. UPDs can cause clinical abnormalities owing to the aberrant dosage of genes regulated by epigenetic imprinting or homozygosity of variants for recessive phenotypes. The aim of this study was to identify the genetic cause of the obesity and developmental delay phenotype in a 3-year-old Chinese boy. STUDY DESIGN: Chromosomal microarray analysis (CMA) was used for detecting potential copy number variations (CNVs) and homozygous segments. Whole-exome sequencing (WES) identified sequence variants. Sanger sequencing further confirmed the variants in GPBAR1 and CAPN10 both in the patient and the parents. RESULTS: No clinically significant CNVs were identified by CMA but a complete UPD of chromosome 2 (UPD2) was revealed in the patient. WES identified a total of 13 rare homozygous single nucleotide variants (SNVs) on chromosome 2. Among the 13 SNVs, a nonsense variation in GPBAR1 (c.753T>G; p.Y251*) and a missense variation in CAPN10 (c.413C>T; p.S138F) were evaluated as candidate disease-causing variants based on their functional impacts to their respective protein and the biological relevance of the genes to the clinical presentation of our patient. Both GPBAR1 and CAPN10 variants were detected in the patient's mother in a heterozygous state, indicating that the patient had maternal UPD2. No other clinically relevant variants were identified. CONCLUSIONS: Homozygosity of rare recessive variations caused by UPD2 likely contributed to the phenotypes of our patient. Based on emerging evidence, the nonsense variation in GPBAR1 and the missense variation in CAPN10 are considered as causally related to our patient's phenotype, that is, obesity and delayed development, respectively. The present study further supports the role of GPBAR1 in obesity and the role of calpain-10 in neurological function. PMID- 27654144 TI - Coping with perceived weight discrimination: testing a theoretical model for examining the relationship between perceived weight discrimination and depressive symptoms in a representative sample of individuals with obesity. AB - BACKGROUND: The association between obesity and perceived weight discrimination has been investigated in several studies. Although there is evidence that perceived weight discrimination is associated with negative outcomes on psychological well-being, there is a lack of research examining possible buffering effects of coping strategies in dealing with experiences of weight discrimination. The present study aims to fill that gap. We examined the relationship between perceived weight discrimination and depressive symptoms and tested whether problem-solving strategies and/or avoidant coping strategies mediated this effect. METHODS: Using structural equation modeling, we analyzed representative cross-sectional data of n=484 German-speaking individuals with obesity (BMI?30 kg m-2), aged 18 years and older. RESULTS: Results revealed a direct effect of perceived weight discrimination on depressive symptoms. Further, the data supported a mediational linkage for avoidant coping strategies, not for problem-solving strategies. Higher scores of perceived weight discrimination experiences were associated with both coping strategies, but only avoidant coping strategies were positively linked to more symptoms of depression. CONCLUSIONS: Perceived weight discrimination was associated with increased depressive symptoms both directly and indirectly through situational coping strategies. Avoidant coping has the potential to exacerbate depressive symptoms, whereas problem solving strategies were ineffective in dealing with experiences of weight discrimination. We emphasize the importance of coping strategies in dealing with experiences of weight discrimination and the need to distinguish between using a strategy and benefiting from it without detriment. PMID- 27654143 TI - Television food advertisement exposure and FTO rs9939609 genotype in relation to excess consumption in children. AB - BACKGROUND/OBJECTIVE: Exposure to food advertisements may cue overeating among children, especially among those genetically predisposed to respond to food cues. We aimed to assess how television food advertisements affect eating in the absence of hunger among children in a randomized trial. We hypothesized that the fat mass and obesity-associated gene (FTO) rs9939609 single-nucleotide polymorphism would modify the effect of food advertisements. SUBJECTS/METHODS: In this randomized experiment, 200 children aged 9-10 years were served a standardized lunch and then shown a 34-min television show embedded with either food or toy advertisements. Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake. Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype. A formal test for interaction of the food advertisement effect on consumption by rs9939609 was conducted. RESULTS: About 172 unrelated participants were included in this analysis. Children consumed on average 453 (s.d.=185) kcals during lunch and 482 (s.d.=274) kcals during the experimental exposure. Children who viewed food advertisements consumed an average of 48 kcals (95% confidence interval: 10, 85; P=0.01) more of a recently advertised food than those who viewed toy advertisements. There was a statistically significant interaction between genotype and food advertisement condition (P for interaction=0.02), where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele, even after controlling for body mass index percentile. CONCLUSIONS: Food advertisement exposure was associated with greater caloric consumption of a recently advertised food, and this effect was modified by an FTO genotype. Future research is needed to understand the neurological mechanism underlying these associations. PMID- 27654145 TI - Examination of the Intolerance of Uncertainty Construct in Youth With Generalized Anxiety Disorder. AB - Intolerance of uncertainty (IU) is a dispositional characteristic reflecting negative cognitive, behavioral, and emotional reactivity in response to events or situations that are uncertain. Although closely associated with a generalized anxiety disorder (GAD) diagnosis in adulthood, IU has received little attention in youth. The goal of this study was to examine the construct in children with GAD and nonanxious children, including its incremental validity in predicting GAD severity and worry beyond anxiety. Ninety-eight children 6 to 11 years of age (51% male; 57% Caucasian) were assessed. The sample included 24 with a GAD diagnosis only (i.e., pure GAD), 36 with GAD plus at least one other disorder (i.e., comorbid GAD), and 38 healthy control children. Clinician, parent, and child reports of IU, anxiety, worry, and GAD severity were collected. Significant differences in levels of IU were found across all three groups; the highest levels in children with comorbid GAD, followed by children with pure GAD, and healthy controls. IU significantly contributed to worry but not GAD severity beyond the effects of anxiety. A significantly larger proportion of self-reported IU data were missing for younger (e.g., 6-8 years) as compared to older children, raising question about the validity of the construct in younger children. Overall findings suggest that IU is not specific to a GAD diagnosis in childhood. IU may instead serve as a broad cognitive risk factor for more severe (e.g., comorbid) forms of affective psychopathology. Future directions for research, including developmental considerations, are discussed. PMID- 27654146 TI - Effects of public and private health insurance on medical service utilization in the National Health Insurance System: National panel study in the Republic of Korea. AB - BACKGROUND: Moral hazard or utilization hazard refers to the phenomenon during which patients overuse medical services under national health insurance (NHI) because the services are free or the patients are required to pay only a portion of the utilization costs. The aim of this study is to investigate how NHI and private health insurance (PHI) systems influence increases in health care utilization rates. METHODS: We designed a longitudinal study to examine the utilization of healthcare services between those insured with NHI or PHI and uninsured Koreans using nationally representative four-year panel data from 13,798 participants. This study was conducted using hierarchical multivariate Poisson regression analyses in which covariates and interaction terms are applied after adjusting for the heterogeneous treatment effect. RESULTS: After adjusting covariates including disease status, lower income Koreans who were covered by medical aid were respectively 2.26 and 1.23 times more likely to receive inpatient care and outpatient care than those who were covered by NHI. When the interaction term of type of insurance was included in the model, those were covered by both medical aid and PHI were respectively 2.38 and 1.25 times more likely to receive inpatient care and outpatient care than those who were covered by only NHI. CONCLUSIONS: The moral hazard behind insurance membership, depending on how NHI maintains policies to confer benefits, may give rise to differences in medical utilization. This phenomenon must be closely monitored to find a way to reform NHI when the rights of medical service consumers are solidified through PHI. PMID- 27654147 TI - Proceedings of the 13th annual conference of INEBRIA. PMID- 27654148 TI - Drug discovery and development in the era of Big Data. PMID- 27654149 TI - Metastatic epidural spinal cord compression. AB - INTRODUCTION: Metastatic epidural spinal cord compression (MESSC) is a frequent event in patients affected by solid tumor metastases. Current available approaches for MESCC include corticosteroids, radiotherapy and surgery. In the last few years, surgery has evolved from decompression by laminectomy alone, with the introduction of instrumentation systems by metalware (screws and hooks), and this has been associated to an improvement of clinical results compared to radiotherapy alone. Areas covered: In this narrative review, we outline the phases of management of cancer patients affected by MESSC, and discuss the timing of treatments, their impact on the Quality of life (QoL), and the relative benefits and harms of surgery and radiotherapy. Expert commentary: Despite the fact that clinical and surgical trials will be required to determine the most appropriate surgical technique and timing of surgery, we do expect a newer and more important role for radiotherapy in the management of MESCC patients in the next future. In particular, the implementation of radiotactic stereosurgery as adjuvant to decompressive surgery is expected to increase in the next few years, above all in those patients that can be candidate to the so called separation surgery. PMID- 27654150 TI - VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells. AB - Targeted delivery of anticancer drugs to brain tumors, especially glioblastoma multiforme, which is the most frequent and aggressive type, is one of the important objectives in nanomedicine. Vascular endothelial growth factor (VEGF) and its receptor type II (VEGFR2) are promising targets because they are overexpressed by not only core tumor cells but also by migrated glioma cells, which are responsible for resistance and rapid progression of brain tumors. The purpose of the present study was to develop the liposomal drug delivery system combining enhanced loading capacity of cisplatin and high binding affinity to glioma cells. This was achieved by using of highly soluble cisplatin analogue, cis-diamminedinitratoplatinum(II), and antibodies against the native form of VEGF or VEGFR2 conjugated to liposome surface. The developed drug delivery system revealed sustained drug release profile, high affinity to antigens, and increased uptake by glioma C6 and U-87 MG cells. Pharmacokinetic study on glioma C6-bearing rats revealed prolonged blood circulation time of the liposomal formulation. The above features enabled the present drug delivery system to overcome both poor pharmacokinetics typical for platinum formulations and low loading capacity typical for conventional liposomal cisplatin formulations. PMID- 27654151 TI - Short-term Suicide Risk After Psychiatric Hospital Discharge. AB - Importance: Although psychiatric inpatients are recognized to be at increased risk for suicide immediately after hospital discharge, little is known about the extent to which their short-term suicide risk varies across groups with major psychiatric disorders. Objective: To describe the risk for suicide during the 90 days after hospital discharge for adults with first-listed diagnoses of depressive disorder, bipolar disorder, schizophrenia, substance use disorder, and other mental disorders in relation to inpatients with diagnoses of nonmental disorders and the general population. Design, Setting, and Participants: This national retrospective longitudinal cohort included inpatients aged 18 to 64 years in the Medicaid program who were discharged with a first-listed diagnosis of a mental disorder (depressive disorder, bipolar disorder, schizophrenia, substance use disorder, and other mental disorder) and a 10% random sample of inpatients with diagnoses of nonmental disorders. The cohort included 770 643 adults in the mental disorder cohort, 1 090 551 adults in the nonmental disorder cohort, and 370 deaths from suicide from January 1, 2001, to December 31, 2007. Data were analyzed from March 5, 2015, to June 6, 2016. Main Outcomes and Measures: Suicide rates per 100 000 person-years were determined for each study group during the 90 days after hospital discharge and the demographically matched US general population. Adjusted hazard ratios (ARHs) of short-term suicide after hospital discharge were also estimated by Cox proportional hazards regression models. Information on suicide as a cause of death was obtained from the National Death Index. Results: In the overall population of 1 861 194 adults (27% men; 73% women; mean [SD] age, 35.4 [13.1] years), suicide rates for the cohorts with depressive disorder (235.1 per 100 000 person-years), bipolar disorder (216.0 per 100 000 person-years), schizophrenia (168.3 per 100 000 person-years), substance use disorder (116.5 per 100 000 person-years), and other mental disorders (160.4 per 100 000 person-years) were substantially higher than corresponding rates for the cohort with nonmental disorders (11.6 per 100 000 person-years) or the US general population (14.2 per 100 000 person-years). Among the cohort with mental disorders, AHRs of suicide were associated with inpatient diagnosis of depressive disorder (AHR, 2.0; 95% CI, 1.4-2.8; reference cohort, substance use disorder), an outpatient diagnosis of schizophrenia (AHR, 1.6; 95% CI, 1.1-2.2), an outpatient diagnosis of bipolar disorder (AHR, 1.6; 95% CI, 1.2-2.1), and an absence of any outpatient health care in the 6 months preceding hospital admission (AHR, 1.7; 95% CI, 1.2-2.5). Conclusions and Relevance: After psychiatric hospital discharge, adults with complex psychopathologic disorders with prominent depressive features, especially patients who are not tied into a system of health care, appear to have a particularly high short-term risk for suicide. PMID- 27654153 TI - In This Issue * October 1, 2016. PMID- 27654152 TI - A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase based nerve agent bioscavengers. AB - A well-considered treatment of acute nerve agents poisoning involves the exogenous administration of butyrylcholinesterase (BChE, EC 3.1.1.8) as a stoichiometric bioscavenger efficient in preventing cholinergic crises caused by acetylcholinesterase (AChE, EC 3.1.1.7) inhibition. An additional improvement in medical countermeasures would be to use oximes that could reactivate BChE as well to upgrade bioscavenging from stoichiometric to oxime-assisted catalytic. Therefore, in this paper we investigated the potency of 39 imidazolium and benzimidazolium oximes (36 compounds synthesized for the first time) to be considered as the reactivators specifically designed for reactivation of phosphylated human BChE. Their efficiency in the reactivation of paraoxon-, VX-, and tabun-inhibited human BChE, as well as human AChE was tested and compared with the efficiencies of HI-6 and obidoxime, used in medical practice today. A comprehensive analysis was performed for the most promising oximes defining kinetic parameters of reactivation as well as interactions with uninhibited BChE. Furthermore, experimental data were compared with computational studies (docking, QSAR analysis) as a starting point in future oxime structure refinement. Considering the strict criteria set for in vivo applications, we determined the cytotoxicity of lead oximes on two cell lines. Among the tested oxime library, one imidazolium compound was selected for preliminary in vivo antidotal study in mice. The obtained protection in VX poisoning outlines its potential in development oxime-assisted OP-bioscavenging with BChE. PMID- 27654154 TI - A golden jubilee for animal welfare protection. PMID- 27654156 TI - Letters to the Editor. PMID- 27654157 TI - Pets and human suicide. PMID- 27654158 TI - What Is Your Diagnosis? PMID- 27654159 TI - Animal Behavior Case of the Month. PMID- 27654160 TI - Pathology in Practice. PMID- 27654161 TI - Pathology in Practice. PMID- 27654162 TI - Vocational choices made by alumni of the Leadership Program for Veterinary Students at Cornell University. AB - OBJECTIVE To compare vocational aspirations and outcomes of participants in the 10-week Leadership Program for Veterinary Students at Cornell University. DESIGN Survey. SAMPLE Veterinary students who participated in the program between 1990 and 2013. PROCEDURES Questionnaires that sought information about the career aspirations of participants at the beginning and end of the program were reviewed, along with records documenting the career progression of participants, audio recordings of interviews conducted with students, and notes of vocation oriented counseling sessions held during each year's program. RESULTS At the conclusion of the program, 143 of 174 (82%) participants indicated they were more likely than not to undertake research training after completing their veterinary degree, compared with 106 of 174 (61%) at the beginning. Participation also stimulated interest in residency training and industry, but did little to promote interest in careers in government or the military. The percentage of participants who indicated they were more likely than not to pursue additional training in private practice decreased from 97 of 174 (56%) at the beginning of the program to 75 of 174 (43%) at the end. Information on career progression was available for 391 individuals, of whom 177 (45%) were pursuing careers of the kind envisioned by the program. However, 189 (48%) participants had a career in general or specialty clinical practice. CONCLUSIONS AND CLINICAL RELEVANCE The Leadership Program appeared to have a short-term influence on careers anticipated by program participants. However, a substantial proportion pursued careers in clinical practice after graduation. PMID- 27654163 TI - Comparison of clinical signs and outcomes between dogs with presumptive ischemic myelopathy and dogs with acute noncompressive nucleus pulposus extrusion. AB - OBJECTIVE To compare clinical signs and outcomes between dogs with presumptive ischemic myelopathy and dogs with presumptive acute noncompressive nucleus pulposus extrusion (ANNPE). DESIGN Retrospective study. ANIMALS 51 dogs with ischemic myelopathy and 42 dogs with ANNPE examined at 1 referral hospital. PROCEDURES Medical records and MRI sequences were reviewed for dogs with a presumptive antemortem diagnosis of ischemic myelopathy or ANNPE. Information regarding signalment, clinical signs at initial examination, and short-term outcome was retrospectively retrieved from patient records. Long-term outcome information was obtained by telephone communication with referring or primary care veterinarians and owners. RESULTS Compared with the hospital population, English Staffordshire Bull Terriers and Border Collies were overrepresented in the ischemic myelopathy and ANNPE groups, respectively. Dogs with ANNPE were significantly older at disease onset and were more likely to have a history of vocalization at onset of clinical signs, have spinal hyperesthesia during initial examination, have a lesion at C1-C5 spinal cord segments, and be ambulatory at hospital discharge, compared with dogs with ischemic myelopathy. Dogs with ischemic myelopathy were more likely to have a lesion at L4-S3 spinal cord segments and have long-term fecal incontinence, compared with dogs with ANNPE. However, long-term quality of life and outcome did not differ between dogs with ischemic myelopathy and dogs with ANNPE. CONCLUSIONS AND CLINICAL RELEVANCE Results revealed differences in clinical signs at initial examination between dogs with ischemic myelopathy and dogs with ANNPE that may aid clinicians in differentiating the 2 conditions. PMID- 27654164 TI - Sensitivity and specificity of manual and automated measurements of reticulocyte parameters for classification of anemia in dogs: 174 cases (1993-2013). AB - OBJECTIVE To assess sensitivity and specificity of manual and automated measurements of reticulocyte percentage, number, and production index for classification of anemia in dogs. DESIGN Retrospective case series SAMPLE 174 blood smears from client-owned dogs with anemia collected between 1993 and 2013 for which reticulocyte parameters were determined manually (nonregenerative anemia, 22; preregenerative anemia, 23; regenerative anemia, 28) or with an automated laser-based counter (nonregenerative anemia, 66; preregenerative anemia, 17; regenerative anemia, 18). PROCEDURES Diagnostic performance was evaluated with receiver operating characteristic (ROC) curves by considering preregenerative anemia as nonregenerative or regenerative. Sensitivity, specificity, and positive likelihood ratio were calculated by use of cutoffs determined from ROC curves or published reference limits. RESULTS Considering preregenerative anemia as non regenerative, areas under the curve (AUCs) for reticulocyte percentage, number, and production index were 97%, 93%, and 91% for manual counting and 93%, 90%, and 93% for automated counting. Sensitivity, specificity, and positive likelihood ratio were 82% to 86%, 82% to 87%, and 4.6 to 6.4, respectively. Considering preregenerative anemia as regenerative, AUCs were 77%, 82%, and 80% for manual counting and 81%, 82%, and 92% for automated counting. Sensitivity, specificity, and positive likelihood ratio were 72% to 74%, 76 to 87%, and 2.7 to 6.2, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Whereas all reticulocyte parameters identified regeneration in anemic dogs, the performance of specific parameters was dependent on the method used. Findings suggested that lower cutoffs than published reference limits are preferred for reticulocyte number and production index and higher cutoffs are preferred for reticulocyte percentage. Reticulocyte production index may be useful when the pretest probability of regeneration is moderate. PMID- 27654165 TI - Perioperative morbidity and outcome of esophageal surgery in dogs and cats: 72 cases (1993-2013). AB - OBJECTIVE To evaluate perioperative morbidity and outcome in dogs and cats undergoing esophageal surgery. DESIGN Retrospective case series. ANIMALS 63 client-owned dogs and 9 client-owned cats. PROCEDURES Medical records of dogs and cats that underwent esophageal surgery were reviewed for information on signalment, history, results of preoperative diagnostic testing, condition treated, details of surgery, intraoperative complications, and postoperative complications. Long-term follow-up data were obtained via veterinarian and client telephone conversations. The relationship between complications and survival to hospital discharge was evaluated by means of regression analysis. RESULTS The most common indication for surgical intervention was an esophageal foreign body in dogs (50/63 [79%]) and esophageal stricture in cats (3/9). Complications were documented in 54% (34/63) of dogs and 3 of 9 cats. The most common immediate postoperative complications were respiratory in nature (9 dogs, 1 cat). Partial esophagectomy and resection with anastomosis were significantly associated with the development of immediate postoperative complications in dogs. The most common delayed postoperative complications were persistent regurgitation (7 dogs) and esophageal stricture formation (3 dogs, 1 cat). For dogs, a mass lesion and increasing lesion size were significantly associated with the development of delayed postoperative complications. Six dogs (10%) and 1 cat died or were euthanized prior to discharge, and pneumomediastinum and leukopenia were negative prognostic factors for dogs being discharged from the hospital. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that the short-term prognosis for dogs and cats that survive surgery for treatment of esophageal lesions is favorable, with 90% of patients discharged from the hospital (57/63 dogs; 8/9 cats). However, dogs treated for more extensive esophageal lesions as well as those undergoing esophagectomy or resection and anastomosis were more likely to develop postoperative complications. PMID- 27654166 TI - Treatment of a perforating thoracic bite wound in a dog with negative pressure wound therapy. AB - CASE DESCRIPTION A 4-year-old male Dachshund was examined following a bite attack that had occurred 5 days previously. The dog had acutely deteriorated despite IV antimicrobial treatment and fluid therapy. CLINICAL FINDINGS On initial examination, the patient was recumbent with signs of septic shock and a flail chest. Three penetrating wounds in the left thoracic wall with malodorous discharge were evident. The animal trauma triage score was 8 out of 18. Thoracic and abdominal radiography revealed displaced fractures of the left seventh, eighth, and ninth ribs and extensive subcutaneous emphysema. Additionally, a marked diffuse bronchointerstitial pattern, areas of alveolar pattern, and pneumothorax were present bilaterally. TREATMENT AND OUTCOME Open surgical debridement with left lateral lung lobectomy and resection of portions of the left thoracic wall were performed. Extensive soft tissue loss precluded primary reconstruction. The defect was stabilized with a polypropylene mesh implant, and negative pressure wound therapy (NPWT) at -100 mm Hg was initiated. Microbial culture and susceptibility testing of tissue samples indicated the presence of multidrug-resistant Staphylococcus pseudintermedius. The NPWT dressing was changed 2, 5, and 7 days after surgery. Treatment was well tolerated, and the mesh was completely covered with granulation tissue 10 days after surgery. On follow-up 5, 7, 12, and 19 months after surgery, the dog was clinically normal with no apparent complications. CLINICAL RELEVANCE Findings suggested that NPWT may be a valuable adjunct when treating small animal patients with severe thoracic trauma. PMID- 27654168 TI - Survey of referring veterinarians' perceptions of and reasons for referring patients to rehabilitation facilities. AB - OBJECTIVE To identify patterns of referral to US small animal rehabilitation facilities, document referring veterinarians' perceptions of rehabilitation services, and examine factors that encouraged and impeded referral of veterinary patients to rehabilitation facilities. DESIGN Cross-sectional survey. SAMPLE 461 completed surveys. PROCEDURES Referral lists were obtained from 9 US rehabilitation facilities, and surveys were emailed or mailed to 2, 738 veterinarians whose names appeared on those lists. Data obtained from respondents were used to generate descriptive statistics and perform chi(2) tests to determine patterns for referral of patients to rehabilitation facilities. RESULTS 461 surveys were completed and returned, resulting in a response rate of 16.8%. The margin of error was < 5% for all responses. Most respondents (324/461 [70.3%]) had referred patients for postoperative rehabilitation therapy. Respondents ranked neurologic disorder as the condition they would most likely consider for referral for future rehabilitation therapy. The most frequently cited reason for not referring a patient for rehabilitation therapy was perceived cost (251/461 [54.4%]) followed by distance to a rehabilitation facility (135/461 [29.3%]). Specialists were more likely than general practitioners to refer patients for rehabilitation therapy. The majority (403/461 [87.4%]) of respondents felt that continuing education in the field of veterinary rehabilitation was lacking. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated a need for continuing education in small animal rehabilitation for veterinarians. Improved knowledge of rehabilitation therapy will enable veterinarians to better understand and more specifically communicate indications and benefits for pets receiving this treatment modality. PMID- 27654167 TI - Surgical management of multiple metatarsal fractures in a chinchilla (Chinchilla lanigera). AB - CASE DESCRIPTION A 3-month-old sexually intact female chinchilla (Chinchilla lanigera) was examined for sudden onset of non-weight-bearing lameness of the right hind limb. CLINICAL FINDINGS On physical examination, the right pes was swollen. An open wound on the medial aspect of the metatarsal region exposed the second metatarsal bone, and the pes was displaced laterally. Radiographs of the right pes revealed oblique displaced fractures of the 4 metatarsal bones. TREATMENT AND OUTCOME Surgical treatment was elected, and enrofloxacin was administered prior to surgery. The protruding fragment of the second metatarsal bone was excised, and the third and fourth metatarsal bones were repaired with intramedullary pins and external skeletal fixation. The chinchilla was bearing weight on the affected limb 9 days after surgery with only mild lameness. The implants were removed 35 days after surgery when radiographs showed bony union of the third and fourth metatarsal bones and continued reduction of the fractures of the second and fifth metatarsal bones. Fifty-six days after surgery, the chinchilla was bearing full weight on the limb, and radiographs showed bony union of the third, fourth, and fifth metatarsal bones. CLINICAL RELEVANCE Findings suggested that intramedullary pinning combined with an epoxy resin external fixator may be an effective technique for metatarsal fracture repair in chinchillas. This method allowed physiologic positioning of the limb and functional hind limb use during fracture healing. Prospective studies of fracture healing in exotic small mammals are indicated. PMID- 27654169 TI - A conjugate of methotrexate and an analog of luteinizing hormone releasing hormone shows increased efficacy against prostate cancer. AB - LHRH receptor, is over-expressed in a variety of human tumors and, is a potential binding site for targeted metastatic prostate cancer therapy. The objectives of our study were to synthesize a bioconjugate of the LHRH analog [DLys6]-LHRH and the anti-tumor agent methotrexate and test the hypothesis that [DLys6]-LHRH-MTX targets and inhibits prostate cancer cell growth in vitro and in vivo. The results of in vitro studies, showed that both [DLys6]-LHRH-MTX and MTX displayed superior cytotoxicity against prostate cancer cells in a concentration-dependent manners, with IC50 concentrations for PC-3 cells of, 1.02 +/- 0.18 MUmol/L and 6.34 +/- 1.01 MUmol/L; for DU-145 cells, 1.53 +/- 0.27 MUmol/L and 8.03 +/- 1.29 MUmol/L; and for LNCaP cells, 1.93 +/- 0.19 MUmol/L and 9.68 +/- 1.24 MUmol/L, respectively. The IC50 values of [DLys6]-LHRH-MTX and MTX were 110.77 +/- 15.31 MUmol/L and 42.33 +/- 7.25 MUmol/L, respectively. Finally, [DLys6]-LHRH-MTX significantly improved the anti-tumor activity of MTX in nude mice bearing PC-3 tumor xenografts. The inhibition ratios of tumor volume and tumor weight in the [DLys6]-LHRH-MTX treated group were significantly higher than those in the MTX treated group. Tumor volume doubling time was also significantly extended from 6.13 days in control animals to 9.67 days in mice treated with [DLys6]-LHRH-MTX. In conclusion, [DLys6]-LHRH -MTX may be useful in treating prostate cancer. PMID- 27654171 TI - Fabrication of magnetic nanoparticles armed with quaternarized N-halamine polymers as recyclable antibacterial agents. AB - Magnetic recyclable bactericidal nanocomposites (Fe3O4@PDMC) were well-designed and prepared by coating of Fe3O4 nanoparticles with quaternarized N-halamine polymers via the free radical polymerization process. In which, 5,5 dimethylhydantoinyl-(3-ethyl-methacrylamine)propyl dimethylammonium bromide (DEMPA), a new monomeric N-halamine precursor, was used as a coating material as well as the dual-functional bactericidal agent. The developed Fe3O4@PDMC nanocomposites exhibited suitable size and super-paramagnetic responsibility. The antibacterial results showed that the Fe3O4@PDMC nanocomposites had excellent biocidal abilities against Staphylococcus aureus (gram-positive) and Escherichia coli (gram-negative). Furthermore, the TTC (Triphenyl Tetrazolium Chloride) dehydrogenase activity assay confirmed that the reductions of the bacteria were mainly attributed to powerful biocidal effects of the coating polymer instead of bacteria capture by the cationic surface. Interestingly, due to the magnetic responsive performance of Fe3O4, the as-prepared Fe3O4@PDMC nanocomposites can be recycled by a magnet and reused for antibacterium through the quenching/rechlorination procedure. All the results presented in this study show that the proposed Fe3O4@PDMC nanocomposites could be a competitive candidate for water purification systems and household sanitation. PMID- 27654170 TI - Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation. AB - Autoimmune diseases mediated by a type of white blood cell-T lymphocytes-are currently treated using mainly broad-spectrum immunosuppressants that can lead to adverse side effects. Antioxidants represent an alternative approach for therapy of autoimmune disorders; however, dietary antioxidants are insufficient to play this role. Antioxidant carbon nanoparticles scavenge reactive oxygen species (ROS) with higher efficacy than dietary and endogenous antioxidants. Furthermore, the affinity of carbon nanoparticles for specific cell types represents an emerging tactic for cell-targeted therapy. Here, we report that nontoxic poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), known scavengers of the ROS superoxide (O2*-) and hydroxyl radical, are preferentially internalized by T lymphocytes over other splenic immune cells. We use this selectivity to inhibit T cell activation without affecting major functions of macrophages, antigen-presenting cells that are crucial for T cell activation. We also demonstrate the in vivo effectiveness of PEG-HCCs in reducing T lymphocyte-mediated inflammation in delayed-type hypersensitivity and in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Our results suggest the preferential targeting of PEG-HCCs to T lymphocytes as a novel approach for T lymphocyte immunomodulation in autoimmune diseases without affecting other immune cells. PMID- 27654173 TI - SmedOB1 is Required for Planarian Homeostasis and Regeneration. AB - The planarian flatworm is an emerging model that is useful for studying homeostasis and regeneration due to its unique adult stem cells (ASCs). Previously, planaria were found to share mammalian TTAGGG chromosome ends and telomerases; however, their telomere protection proteins have not yet been identified. In Schmidtea mediterranea, we identified a homologue of the human protection of telomeres 1 (POT1) with an OB-fold (SmedOB1). SmedOB1 is evolutionarily conserved among species and is ubiquitously expressed throughout the whole body. Feeding with SmedOB1 double-stranded RNAs (dsRNAs) led to homeostasis abnormalities in the head and pharynx. Furthermore, several ASC progeny markers were downregulated, and regeneration was impaired. Here we found that SmedOB1 is required for telomeric DNA-protein complex formation and it associates with the telomere TTAGGG sequence in vitro. Moreover, DNA damage and apoptosis signals in planarian were significantly affected by SmedOB1 RNAi. We also confirmed these phenotypes in Dugesia japonica, another flatworm species. Our work identified a novel telomere-associated protein SmedOB1 in planarian, which is required for planarian homeostasis and regeneration. The phylogenetic and functional conservations of SmedOB1 provide one mechanism by which planarians maintain telomere and genome stability to ensure their immortality and shed light on the regeneration medicine of humans. PMID- 27654172 TI - Mobile small RNAs and their role in regulating cytosine methylation of DNA. AB - Small (s)RNAs of 21 to 24 nucleotides are associated with RNA silencing and methylation of DNA cytosine residues. All sizes can move from cell-to-cell and long distance in plants, directing RNA silencing in destination cells. Twenty four nucleotide sRNAs are the predominant long-distance mobile species. Thousands move from shoot to root, where they target methylation of transposable elements both directly and indirectly. We derive several classes of interaction between small RNAs and methylation and use these to explore the mechanisms of methylation and gene expression that associate with mobile sRNA signaling. PMID- 27654175 TI - Editorial. AB - A 'care lottery' is how the health committee branded the current inequities in health and social care provision for elderly people. In a report which was highly critical of the government's stance, the health committee called for national guidelines on eligibility criteria for NHS funded care. The committee also called for better discharge procedures, which ensured a 'package of care' for elderly people, and a charter for long term care to be established, which would set minimum standards for patients regardless of where they live. PMID- 27654176 TI - MPs say NHS must fund long term care. AB - Nurses have welcomed recommendations from the Commons health committee last week which call for people to have the right to NHS funded, long term nursing care. PMID- 27654174 TI - Removal of proprioception by BCI raises a stronger body ownership illusion in control of a humanlike robot. AB - Body ownership illusions provide evidence that our sense of self is not coherent and can be extended to non-body objects. Studying about these illusions gives us practical tools to understand the brain mechanisms that underlie body recognition and the experience of self. We previously introduced an illusion of body ownership transfer (BOT) for operators of a very humanlike robot. This sensation of owning the robot's body was confirmed when operators controlled the robot either by performing the desired motion with their body (motion-control) or by employing a brain-computer interface (BCI) that translated motor imagery commands to robot movement (BCI-control). The interesting observation during BCI-control was that the illusion could be induced even with a noticeable delay in the BCI system. Temporal discrepancy has always shown critical weakening effects on body ownership illusions. However the delay-robustness of BOT during BCI-control raised a question about the interaction between the proprioceptive inputs and delayed visual feedback in agency-driven illusions. In this work, we compared the intensity of BOT illusion for operators in two conditions; motion-control and BCI control. Our results revealed a significantly stronger BOT illusion for the case of BCI-control. This finding highlights BCI's potential in inducing stronger agency-driven illusions by building a direct communication between the brain and controlled body, and therefore removing awareness from the subject's own body. PMID- 27654177 TI - Nurses under pressure after West trial. AB - Health visitors in Gloucester are under pressure because publicity surrounding the Rosemary West trail has encouraged more families to disclose sexual and physical abuse. PMID- 27654178 TI - ? AB - NHS cuts, 1840s style: the amputation of a child's leg in the early 19th century was reconstructed by staff at the Thackray Medical Museum, Leeds, last week. The museum has just been awarded L3 million pounds of National lottery money and Ls due to open at Easter 1997. PMID- 27654181 TI - Evidence shows more patients prefer to be treated by nurses. AB - Calls for more specialist training to enable nurses to substitute for doctors have been made by an influential parliamentary inquiry. PMID- 27654179 TI - Employers complacent over growing shortage of nurses. AB - Nursing shortages are worsening according to the government's own figures, the Royal College of Nursing claims in new evidence to the pay Review Body published this week. PMID- 27654182 TI - ? AB - Health Visitors' Association director Margaret Buttigieg, above, Is to resign early next year to become regional nurse director for the NHS Executive's south and west region. PMID- 27654183 TI - Widow sues over stress-related suicide. AB - The widow of a mental health nurse who hanged himself is suing an NHS trust for L50,000. PMID- 27654184 TI - No-smoking message to soaps. AB - Trainee scriptwriters are being encouraged by the Royal College of Nursing to include no-smoking messages in storylines. PMID- 27654185 TI - Hospital's 'no lifting' policy reduces back injuries by half. AB - Back injuries to nurses at a top Glasgow hospital have halved since a 'no lifting' policy was introduced, a Royal College of Nursing safety officers conference was told last week. PMID- 27654187 TI - RCN presses for action on racism. AB - The Royal College of Nursing will press for legal action to tackle racial harassment of nurses at a meeting with the Commission for Racial Equality next week. PMID- 27654186 TI - Washing uniforms at home may break rules. AB - Nurses were warned last week that they may be in breach of health and safety regulations if they take their uniforms home to wash. PMID- 27654188 TI - ? AB - Five nurses, including Amanda McCay, Geraldine Dunne, Jane James and Ruth Blackburn, pictured from left, last week became the first recipients of a BSc in child health studies from the RCN Institute. PMID- 27654190 TI - Move to help nurses rejoin NHS pension scheme. AB - Nurses mislead into opting out of the NHS pension scheme received a boost last week when the government made it easier for them to rejoin by cutting charges levied to insurance companies. PMID- 27654191 TI - Ombudsman criticises staff for poor communication. AB - Nurses who gave a stroke patient the wrong diet and did not supervise her properly at night were among NHS staff criticised in the latest report by the health service ombudsman. PMID- 27654193 TI - Nursing unions in ireland to ballot on action over pay. AB - Ireland's four nursing unions are to ballot their 25,000 members in January for a strike mandate to secure a major upgrade in pay scales. PMID- 27654192 TI - Danish government doubles pay offer. AB - Nurses in Denmark are claiming victory in their long running pay dispute after they won a rise double the government's initial 3.5 per cent offer. PMID- 27654194 TI - Patient controlled analgesia means better pain control. AB - Nurses need a better understanding of pain management and the benefits of patient controlled analgesia (PCA), nurses were told at the launch of a new PCA resource pack. PMID- 27654195 TI - Guidelines improve nutrition in ITU. AB - The introduction of nutritional guidelines has resulted in a significant reduction in the time taken to initiate feeding of intubated patients. PMID- 27654196 TI - Helping people cope in the community. AB - Psychological treatment in addition to drugs might help people with schizophrenia cope better in community settings, according to researchers. PMID- 27654197 TI - Teachers' input with asthmatic children. AB - An increased knowledge of asthma among teachers is associated with an improved ability to help asthmatic children lead a normal life and potentially reduces the risks of an attack. PMID- 27654198 TI - Photographic screening for retinopathy. AB - A photographic method for detecting diabetic eye disease should be the preferred option in national, community based screening programmes, Liverpool researchers report. PMID- 27654199 TI - Crisis of silence. AB - HIV infection and AIDS are overwhelmingly perceived as a younger persons' issue, but the latest statistics show that 7 per cent of men with HIV are aged over 50 rising to 11 per cent of those with AIDS ( 1 ), and there is no reason to expect these proportions to decline in the near future; some predict that they will increase. PMID- 27654200 TI - Doing it for themselves. AB - There is a cornucopia of writing about clinical supervision, with assertions about how important it is and how it ensures safe practice. There have been recommendations from the Allitt inquiry about its introduction, yet there is only the sketchiest information about how to do it and introduce it effectively within a trust to the satisfaction of both professional clinical staff and managers with an eye to the financial bottom line. PMID- 27654201 TI - Quality of life affects nurses' morale too. AB - Well done Ruth Greene ('The machine breaks', Viewpoint November 8). PMID- 27654202 TI - Where is the evidence to back counselling? AB - The responses to my letter regarding counselling have so far been disappointing since neither has really addressed the issue of whether it is effective or a waste of limited resources. PMID- 27654203 TI - More prejudice over rank than colour. AB - On the subject of racism and prejudice ('Nursing in a multi-ethnic NHS,' News and editorial November 8), I have experienced more prejudice because I am an EN than because I am an Asian. PMID- 27654204 TI - Bring your own blankets in new NHS. AB - I did enjoy reading the comments of newly qualified staff in 'What do you miss about the old-style NHS?' (Viewpoint November 1). PMID- 27654205 TI - Take comfort that you are saving lives. AB - I was recently admitted to St Peter's Hospital, Chertsey with a serious complication of pregnancy, eclampsia. PMID- 27654206 TI - Inter-agency training gets positive response. AB - It was interesting to read the article by Professor Wendy Couchman, 'Joint education for mental health teams' (Clinical November 8). PMID- 27654208 TI - Let's fight cutbacks and not each other. AB - After reading 'Essential skills being lost in new NHS' (Letters November 15) I feel I have to comment in defence of auxiliary staff and NVQs. PMID- 27654207 TI - Some things don't add up. AB - Further to Malcolm Wing's letter about the Unison- brokered pay deal 'Pay deal secures RB's future' (Letters November 8), the RCN represents 75 per cent of registered nurses in the NHS, Unison's claim to represent 240,000 nurses is simply not possible. Presumably, they meant to say 240,000 nursing and related staff? PMID- 27654209 TI - Mixed feelings over pill warnings. AB - It has been with confused feelings that I followed the recent coverage of the government's supposedly alarmist announcement that seven brands of contraceptive pill increase the risk of blood clots. PMID- 27654210 TI - Information exchange. AB - * We are staff nurses working within the Day Case Unit at Blackburn Royal Infirmary. As our unit is relatively new, we are looking towards improving our nursing care by devising new nursing care plans for our clients. We would like copies of nursing care plans and details of the nursing model on which it is based. PMID- 27654212 TI - David's story. AB - David has had six previous admissions to hospital. On each admission he had been violent towards nursing staff. PMID- 27654211 TI - Nurses valued! AB - Is it me or has anyone else noticed that doctors and the medical profession have finally woken up to the fact that nursing has value? PMID- 27654214 TI - Listing. AB - As there is such a huge demand for the publication of free listings, readers may wish to take advantage of a new service being launched by Nursing Standard, for further details see the coupon in the appointments section or contact Kim Boudler, telephone 0181 423 1066. PMID- 27654213 TI - Readers panel - Should we all be nurse pracitioners? AB - Our experts consider a hot topic of the day. PMID- 27654216 TI - Adolescent Cannabinoid Use and Cognition; Unexpected Results from a Rat Model of Cannabinoid Self-Administration. PMID- 27654217 TI - Are women more likely to self-test? A short report from an acceptability study of the HIV self-testing kit in South Africa. AB - This study assessed the acceptability of, as well as the facilitators of and barriers to the HIV self-testing kit in the Gauteng province, South Africa. An exploratory qualitative cross-sectional study was conducted using focus group discussions (FGDs) among a sample of 118 respondents selected from the Braamfontein and Soweto areas of Johannesburg. Sixteen FGDs were conducted in order to assess the acceptability of the HIV self-testing kit. Respondent groups were segmented according to area (Soweto or Braamfontein), gender (male or female), age (20-34 and 35-49 years of age) and HIV testing status (have previously tested for HIV or have never tested for HIV) in order to achieve maximum variability. The main advantage identified was that the self-testing kit allows for privacy and confidentiality with regard to HIV status, and does not require a visit to a health facility - two of the main barriers to current HIV counselling and testing uptake. However, respondents, predominantly males, were concerned about the lack of counselling involved, which they thought could lead to suicide ideation among testers. The HIV self-testing kit was found to be acceptable among the majority of respondents. However, there is still a need for follow-up services for self-testers. The idea of a hotline for telephonic counselling within the self-testing model seemed to be favourable among many respondents and is an alternative to traditional face-to-face counselling, although some respondents felt that this was not sufficient. PMID- 27654218 TI - Synthesis and biological evaluation of a series of N-alkylated imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors. AB - In this paper, we report the synthesis and biological evaluation of a series of 1,5- and 1,4- substituted derivatives of 1H-imidazol-4-ylacetic acid, a series of 1,2-substituted 3-(1H-imidazol-2-yl)propanoic acid and an N-substituted (2E)-3 (1H-imidazol-2-yl)prop-2-enoic acid as new mGAT3 inhibitors. The lipophilic moieties attached to the N-atom of the parent structures were delineated from the 2-[9-(4-methoxyphenyl)-9H-fluoren-9-yl]oxyethyl residue, known from a prototypic mGAT3 inhibitor. For the structure-activity-relationship studies, the spacer between the N-atom of the imidazole ring and the 2-[9-(4-methoxyphenyl)-9H fluoren-9-yl] moiety was varied in length from three to six atoms, and in nature being either a pure saturated or unsaturated alkyl chain or an alkyl chain containing up to two ether functions. The compounds were characterized for inhibitory potencies at mouse GABA transporter proteins mGAT1-mGAT4. Among the 1,2-substituted compounds, the N-alkylated (2E)-3-(1H-imidazol-2-yl)prop-2-enoic acid 12e containing a C5O spacer exhibits a pIC50 value of 5.13 +/- 0.04 at mGAT3, but is devoid of significant selectivity for this GABA transporter. However, the inhibitory potency displayed by 12e at mGAT3 nominally surpasses that of SNAP-5294 reported as the most potent inhibitor of mGAT3 so far. PMID- 27654219 TI - Protective effects of the selective alpha1A-adrenoceptor antagonist silodosin against cyclophosphamide-induced cystitis in rats. AB - We investigated the protective effects of a selective alpha1A-adrenoceptor antagonist, silodosin (Silod) on urinary bladder function in cyclophosphamide (CYP)-induced cystitis rats, with and without desensitization of the capsaicin (CAP)-sensitive afferent nerve pathway. Male Wistar rats (310-400 g) were pretreated with Silod (0, 100, or 300 MUg/kg/day, p.o.) for 1 week before cystometry, and were administered either CYP (150 mg/kg, i.p.) or saline 2 days before the experiment. In another experiment, the rats were treated with CAP (125 mg/kg, s.c.) 4 days before the cystometry. The rat bladders were harvested, weighed, and evaluated histologically. The cystometric evaluation showed significant reductions in the intercontraction interval (ICI), single voided volume (SVV), and bladder compliance in CYP-treated rats compared to those in the vehicle-treated rats. High-dose Silod or CAP treatment significantly increased the ICI and SVV in the CYP rats. However, high-dose Silod treatment did not increase the ICI and SVV in CAP-treated CYP rats. Treatment with Silod did not improve the bladder weight, edema, and leukocyte infiltration resulting from the CYP-induced bladder inflammation. These data suggest that blockade of alpha1 adrenoceptors by Silod inhibited the CAP-sensitive afferent pathway in rats with cystitis. PMID- 27654220 TI - Superhydrophobic Surface With Shape Memory Micro/Nanostructure and Its Application in Rewritable Chip for Droplet Storage. AB - Recently, superhydrophobic surfaces with tunable wettability have aroused much attention. Noticeably, almost all present smart performances rely on the variation of surface chemistry on static micro/nanostructure, to obtain a surface with dynamically tunable micro/nanostructure, especially that can memorize and keep different micro/nanostructures and related wettabilities, is still a challenge. Herein, by creating micro/nanostructured arrays on shape memory polymer, a superhydrophobic surface that has shape memory ability in changing and recovering its hierarchical structures and related wettabilities was reported. Meanwhile, the surface was successfully used in the rewritable functional chip for droplet storage by designing microstructure-dependent patterns, which breaks through current research that structure patterns cannot be reprogrammed. This article advances a superhydrophobic surface with shape memory hierarchical structure and the application in rewritable functional chip, which could start some fresh ideas for the development of smart superhydrophobic surface. PMID- 27654221 TI - Beta-agonist residues in cattle, chicken and swine livers at the wet market and the environmental impacts of wastewater from livestock farms in Selangor State, Malaysia. AB - Fourteen beta-agonists were quantitatively analyzed in cattle, chicken and swine liver specimens purchased at 14 wet markets in Selangor State, Malaysia, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The health risks of ractopamine and clenbuterol residues in the Malaysian population were assessed based on quantitative data and meat consumption statistics in Malaysia. Wastewater samples collected at swine farms (n = 2) and cattle/cow farms (n = 2) in the Kuala Langat district were analyzed for the presence for the 14 compounds. Wastewater in chicken farms was not collected because there was negligible discharge during the breeding period. The environmental impacts caused by beta agonists discharged from livestock farms were spatially assessed in the Langat River basin using a geographic information system (GIS). As a result, 10 compounds were detected in the liver specimens. Ractopamine, which is a permitted compound for swine in Malaysia, was frequently detected in swine livers; also, 9 other compounds that are prohibited compounds could be illegally abused among livestock farms. The health risks of ractopamine and clenbuterol were assessed to be minimal as their hazard quotients were no more than 7.82 * 10-4 and 2.71 * 10 3, respectively. Five beta-agonists were detected in the wastewater samples, and ractopamine in the swine farm resulted in the highest contamination (30.1 MUg/L). The environmental impacts of the beta-agonists in the Langat River basin were generally concluded to be minimal, but the ractopamine contamination released from swine farms was localized in coastal areas near the estuary of the Langat River basin because most swine farms were located in that region. PMID- 27654215 TI - Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions. AB - The evidence to date, coupled with advances in immunology and genetics has afforded the field an unparalleled opportunity to investigate the hypothesis that a subset of patients with schizophrenia may manifest an immunophenotype, toward new potential diagnostics and therapeutics to reduce risk, alleviate symptoms, and improve quality of life in both at-risk populations and patients with established schizophrenia. In this paper, we will first summarize the findings on immune dysfunction in schizophrenia, including (1) genetic, prenatal, and premorbid immune risk factors and (2) immune markers across the clinical course of the disorder, including cytokines; C-reactive protein; immune cells; antibodies, autoantibodies and comorbid autoimmune disorders; complement; oxidative stress; imaging of neuroinflammation; infections; and clinical trials of anti-inflammatory agents and immunotherapy. We will then discuss a potential mechanistic framework toward increased understanding of a potential schizophrenia immunophenotype. We will then critically appraise the existing literature, and discuss suggestions for the future research agenda in this area that are needed to rigorously evaluate this hypothesis. PMID- 27654222 TI - Effect of oxidation and catalytic reduction of trace organic contaminants on their activated carbon adsorption. AB - The combination of ozonation and activated carbon (AC) adsorption is an established technology for removal of trace organic contaminants (TrOCs). In contrast to oxidation, reduction of TrOCs has recently gained attention as well, however less attention has gone to the combination of reduction with AC adsorption. In addition, no literature has compared the removal behavior of reduction vs. ozonation by-products by AC. In this study, the effect of pre ozonation vs pre-catalytic reduction on the AC adsorption efficiency of five TrOCs and their by-products was compared. All compounds were susceptible to oxidation and reduction, however the catalytic reductive treatment proved to be a slower reaction than ozonation. New oxidation products were identified for dinoseb and new reduction products were identified for carbamazepine, bromoxynil and dinoseb. In terms of compatibility with AC adsorption, the influence of the oxidative and reductive pretreatments proved to be compound dependent. Oxidation products of bromoxynil and diatrizoic acid adsorbed better than their parent TrOCs, but oxidation products of atrazine, carbamazepine and dinoseb showed a decreased adsorption. The reductive pre-treatment showed an enhanced AC adsorption for dinoseb and a major enhancement for diatrizoic acid. For atrazine and bromoxynil, no clear influence on adsorption was noted, while for carbamazepine, the reductive pretreatment resulted in a decreased AC affinity. It may thus be concluded that when targeting mixtures of TrOCs, a trade-off will undoubtedly have to be made towards overall reactivity and removal of the different constituents, since no single treatment proves to be superior to the other. PMID- 27654223 TI - Reverse osmosis brine for phosphorus recovery from source separated urine. AB - Phosphorus (P) recovery from waste streams has recently been recognized as a key step in the sustainable supply of this indispensable and non-renewable resource. The feasibility of using brine from a reverse osmosis (RO) membrane unit treating cooling water as a precipitant for P recovery from source separated urine was evaluated in the present study. P removal efficiency, process parameters and precipitate properties were investigated in batch and continuous flow experiments. More than 90% of P removal was obtained from both undiluted fresh and hydrolyzed urines by mixing with RO brine (1:1, v/v) at a pH over 9.0. Around 2.58 and 1.24 Kg of precipitates could be recovered from 1 m3 hydrolyzed and fresh urine, respectively, and the precipitated solids contain 8.1-19.0% of P, 10.3-15.2% of Ca, 3.7-5.0% of Mg and 0.1-3.5% of ammonium nitrogen. Satisfactory P removal performance was also achieved in a continuous flow precipitation reactor with a hydraulic retention time of 3-6 h. RO brine could be considered as urinal and toilet flush water despite of a marginally higher precipitation tendency than tap water. This study provides a widely available, low - cost and efficient precipitant for P recovery in urban areas, which will make P recovery from urine more economically attractive. PMID- 27654224 TI - An efficient approach for phosphorus recovery from wastewater using series coupled air-agitated crystallization reactors. AB - Homogeneous nucleation of hydroxyapatite (HAP) crystallization in high levels of supersaturation solution has a negative effect on phosphorus recovery efficiency because of the poor settleability of the generated HAP microcrystalline. In this study, a new high-performance approach for phosphorus recovery from anaerobic supernatant using three series-coupled air-agitated crystallization reactors was developed and characterized. During 30-day operation, the proposed process showed a high recovery efficiency (~95.82%) and low microcrystalline ratio (~3.11%). Particle size analysis showed that the microcrystalline size was successively increased (from 5.81 to 26.32 MUm) with the sequence of series-coupled reactors, confirming the conjectural mechanism that a multistage-induced crystallization system provided an appropriate condition for the growth, aggregation, and precipitation of crystallized products. Furthermore, the new process showed a broad spectrum of handling ability for different concentrations of phosphorus containing solution in the range of 5-350 mg L-1, and the obtained results of phosphorus conversion ratio and recovery efficiency were more than 92% and 80%, respectively. Overall, these results showed that the new process exhibited an excellent ability of efficient phosphorus recovery as well as wide application scope, and might be used as an effective approach for phosphorus removal and recovery from wastewater. PMID- 27654226 TI - Perspectives in Psychiatric Nursing: Thoughts From Our Early Leaders. PMID- 27654227 TI - Posttraumatic Stress Disorder and Its Predictors in Disaster-Bereaved Survivors. PMID- 27654225 TI - Exacerbation of pre-existing diabetes insipidus during pregnancy, mechanisms and management. AB - During pregnancy, physiological changes in osmotic homeostasis cause water retention. If excessive, this can cause gestational diabetes insipidus (DI), particularly in patients with already impaired vasopressin secretion. We present the case of a 34-year-old patient with pre-existing hypopituitarism who experienced a transient exacerbation of her DI during a twin pregnancy. In contrast to typical gestational DI, polyuria and polydipsia occurred during the first trimester and remained stable thereafter. This case highlights a challenging clinical entity of which pathophysiology, diagnostic approach and treatment will be discussed. PMID- 27654228 TI - Coping with Violence in Mental Health Care Settings: Patient and Staff Member Perspectives on De-escalation Practices. AB - This multiple case study explored de-escalation processes in threatening and violent situations based on patients and staff members perspectives. Our post hoc analysis indicated that de-escalation included responsive interactions influenced by the perspectives of both patients and staff members. We assembled their perspectives in a mental model consisting of three interdependent stages: (1) memories and hope, (2) safety and creativity and (3) reflective moments. The data indicated that both patients and staff strived for peaceful solutions and that a dynamic and sociological understanding of de-escalation can foster shared problem solving in violent and threatening situations. PMID- 27654229 TI - Effects of Relaxation Exercises and Music Therapy on the Psychological Symptoms and Depression Levels of Patients with Schizophrenia. AB - PURPOSE: This study aims to identify the effects of relaxation exercises and music therapy on the psychological symptoms and depression levels of patients with chronic schizophrenia. MATERIALS AND METHODS: This semi-experimental study was conducted using pre- and post-tests with a control group. The study population consists of patients with schizophrenia who regularly attended community mental health centers in the Malatya and Elazig provinces of Turkey between May 2015 and September 2015. The study's sample consists of 70 patients with schizophrenia (n=35 in the control group; n=35 in the experimental group) who were selected randomly based on power analysis. The "Patient Information Form," the "Brief Psychiatric Rating Scale (BPRS)" and the "Calgary Depression Scale for Schizophrenia (CDSS)" were used for data collection. Patients in the experimental group participated in relaxation exercises and music therapy 5 times a week for 4 weeks. The experimental group of 35 persons was divided into three groups of approximately 10-12 individuals in order to enable all participants to attend the program. No intervention was applied to the patients in the control group. The data were evaluated using percentage distribution, arithmetic means, standard deviations, Chi-square and independent samples t-tests. RESULTS: The study found that patients in the experimental group showed a decrease in total mean scores on the BPRS and CDSS; the difference between the post-test scores of the experimental group and the post-test scores of the control group was statistically significant (p<0.05). The practice of relaxation exercises and music therapy was proven to be effective in reducing schizophrenic patients' psychological symptoms and levels of depression. CONCLUSION: Relaxation exercises and music therapy can be used as a complementary therapy in the medical treatment of patients with chronic schizophrenia. PMID- 27654230 TI - Predictors of Depression Among Community-Dwelling Older Women Living Alone in Korea. AB - This study examined the prevalence and predicting factors of depression among community-dwelling older women living alone in Korea. Of the 2054 older women living alone in this study, 42.9% (881) were experiencing depression. Factors associated with a higher prevalence of depression were overall difficulty with living alone, taking more than six medications, limitations of instrumental activities of daily living, limitations of muscle strength, limitations of exercise performance in upper extremities, trouble with hearing, and perceptions of poor health status. These results provide a basis for designing preventive interventional programs to decrease depression among older women living alone in Korea. PMID- 27654231 TI - Psychological Adjustment of Infertile Men Undergoing Fertility Treatments: An Association With Sperm Parameters. AB - BACKGROUND: The difficulties in the psychological adaptation to the infertility diagnosis and assisted reproductive technology (ART) treatments have shown influence on the sperm quality. The biological and psychological aspects of infertility seem not to be independent. OBJECTIVE: To analyze the impact of depressive symptoms, anxiety, dyadic adjustment and infertility stress on the sperm quality of the men proposed to ART first or repeated experience. MATERIALS AND METHODS: This transversal study was conducted in the Medically Assisted Reproduction Unit of Centro Hospitalar de Sao Joao, in Porto, Portugal. 112 men with infertility diagnosis were included to initiate an ART cycle. Participants completed the Inventory State-Trait Anxiety-Form Y (STAI-Y), the Beck Depression Inventory-II (BDI-II), the Dyadic Adjustment Scale (DAS) and the Inventory of Fertility Problems (IFP) before the beginning of the treatment. RESULTS: The state-anxiety had a negative linear impact on the slow progressive motility (p<0.05). However, depressive symptoms assumed a suppressor effect on this variable, enhancing its importance as a predictor. CONCLUSION: Results show that psychopathological symptoms before an ART cycle can influence the sperm motility. However, this association seems to only be present in men undergoing first experience ART treatments. Thus, this research shows the need for mental health professionals to respond to emotional difficulties of the male gender, through the development of psychological interventions adjusted, so as to minimize the impact of exposure to ART treatments. PMID- 27654232 TI - Responses and Results to Ethical Problems by Psychiatric Nurses in Japan. AB - The aim of this study was to investigate the responses of Japanese psychiatric nurses to ethical problems, and the results of those issues. The participants were 130 nurses who worked in psychiatry wards in a hospital. The nurses answered the question "how did you respond when you faced an ethical problem and what results did you get?" in free description. Seven categories were selected qualitatively from their responses: "Lack of action and no change," "Experiencing problems and feeling gloomy," "Pointing out misconduct and being hurt," "Consultation among staff and resolution or not," "Consultation with physicians and getting positive or negative responses," and "Searching for and providing evidence-based care," and "Thinking for themselves." The facts that some nurses do not cope with ethical problems and some face moral distress without knowing what to do suggest that "improvement of moral efficacy to cope with ethical problems", "proposing resolution methods", and "organizational ethics support" may be useful. PMID- 27654233 TI - Stress in Persons with Dementia: Benefits of a Memory Center Day Program. AB - Most persons with dementia are cared for by family members who are so overwhelmed that their mental and physical health declines. Adult day care programs (ADC) are growing in number to meet caregivers' needs for respite but little is known about their effect on enrollee mental health. We examined mental health of enrollees (stress, anxiety, mood, emotions) and arousal (blood pressure and salivary cortisol) from day program enrollment to 3 months following enrollment. Results showed significant decreases in morning cortisol level at 1 and 3 months (p=.047). Perceived stress decreased at 1 and 3 months measured by Perceived Stress Scale (p=.03) and Index of Clinical Stress (p=.01). Results provide support for ADC as a stress-reducing environment for individuals with mild to moderate cognitive impairment. Future studies should be conducted to examine which elements of ADC are beneficial. PMID- 27654234 TI - Factors Affecting Suicidal Ideation Among Middle-Aged Korean Women in an Urban Rural Province. AB - PURPOSE: This study aimed to investigate the factors that affect suicidal ideation among middle-aged Korean women in an urban-rural province. METHODS: This study used a convenience sample consisting of 196 middle-aged Korean women who live in Gyeonggi Province. Data were collected between November 2013 and January 2014. RESULTS: There were significant correlations among social relationships (r= .18, p=.013), previous experiences of violence (r=.15, p=.032), subjective happiness (r=-.36, p<.001), depression (r=.44, p<.001), and suicidal ideation. Economic status, subjective happiness, and depression were found to have an effect on suicidal ideation (R(2)=.26). CONCLUSIONS: The study's results demonstrate that there needs to be greater focus on middle-aged women when considering mental health interventions in rural areas of Korea. The results may also contribute to the development of improved interventions for psychological health care. PMID- 27654235 TI - Perceptions and Feelings of Fathers of Children With Down Syndrome. AB - PURPOSE: This study aimed to obtain information about the lives of families with children with Down syndrome through interviews with the fathers. METHODS: The participants were 9 fathers who were recruited from the local Association of Parents of Down syndrome. Their children were born between 1996 and 2009. The study used a descriptive exploratory design utilizing a focus group. RESULTS: Through analysis of the fathers' transcripts, 7 major themes emerged: 1) crisis of life, 2) emotional turmoil, 3) attitudes toward the disability, 4) parental responsibility, 5) realization of fatherhood, 6) difference of feelings between mother and father, and 7) contact with people. CONCLUSIONS: Fathers were upset with the fact that their children were born with Down syndrome. However, they accepted fatherhood through child-rearing in cooperation with others. The experience of fathers in this study provides practical points for caring for families with children with Down syndrome. PMID- 27654237 TI - Finding Identity and Meaning as a Nurse with a Mental Illness. AB - Through professional acculturation, nurses establish their identities as nurses. They also develop of an understanding what mental illness and associated phenomena mean. When nurses themselves develop mental illness, they must learn to establish a new identity as a patient and more specifically as a nurse-patient, and come to a new understanding of what mental illness means to them. This autoethnographic paper focuses on the author's own experience of finding an identity as nurse-patient and discovering what that really meant, at the same time incorporating analysis to connect the personal and the cultural. PMID- 27654236 TI - How the Illness Management and Recovery Program Enhanced Recovery of Persons With Schizophrenia and Other Psychotic Disorders: A Qualitative Study. AB - This study aims to describe how the Illness Management and Recovery program enhanced recovery of persons with schizophrenia and other psychotic disorders from their own perspective. Participants valued learning how to divide huge goals into attainable steps, how to recognize and prevent a relapse by managing symptoms, practicing skills, and talking openly about illness related experience. They learned from the exchange with peers and from the information in the IMR textbook. Nurses should have continuous attention and reinforcement for progress on goals, skills practice and exchange of peer information. A peer-support specialist can contribute to keep this focus. PMID- 27654238 TI - Perceived Control among People with Severe Mental Illness: A Comparative Study. AB - BACKGROUND: Given the importance of perceived control to mental health and recovery, research is needed to determine strategies to increase perceived control for people with a mental illness. AIM: Investigate the implications of a therapeutic recreation program on the perceived control of people with a mental illness. METHOD: Participants of an intervention group (n=27) and comparison group (n=18) completed the Perceived Control Across Domains Scale at three time intervals. Subscale and total scores were analysed. RESULTS AND DISCUSSION: Significant variation occurred in the perceived control areas of substance use, personal cognition and personal empowerment. IMPLICATIONS: A unique nurse led therapeutic recreation initiative, such as Recovery Camp, can improve and maintain facets of perceived control among people with mental illness. PMID- 27654239 TI - Toward Treatment Integrity: Developing an Approach to Measure the Treatment Integrity of a Dialectical Behavior Therapy Intervention With Homeless Youth in the Community. AB - The current paper discusses an approach to measuring treatment integrity of dialectical behavioral therapy (DBT) when implemented within two programs providing services to street-involved youth in the community. Measuring treatment integrity is a critical component of effective implementation of evidence-based interventions in clinical practice, since sound treatment integrity increases confidence in client outcomes and intervention replicability. Despite being an essential part of implementation science, few studies report on treatment integrity, with limited research addressing either measurement tools or maintenance of treatment integrity. To address the lack of available treatment integrity measures, researchers in the current study developed and piloted a treatment integrity measure which pertain to the individual and group components of DBT. A total of 20 recordings were assessed using the treatment integrity measure. Results indicate that the community agency staff (e.g. youth workers, social workers & nurses) implemented the intervention as intended; increasing confidence in the outcome variables, the staffs' training and the replicability of the intervention. This article offers one approach to addressing treatment integrity when implementing evidence-based interventions, such as DBT in a community setting, and discusses the need for effective and feasible integrity measures that can be adopted in order to strengthen mental health practice in community settings. PMID- 27654240 TI - Exploring the Experience of Self-Diagnosis of Autism Spectrum Disorder in Adults. AB - One in 68 Americans has autism spectrum disorder (ASD), and diagnosis is often delayed into adulthood in individuals without comorbid intellectual disability. Many undiagnosed adults resort to self-diagnosis. The purpose of this descriptive phenomenology was to explore the experience of realizing a self-diagnosis of ASD among 37 individuals who were not formally diagnosed. Results revealed five themes: feeling "othered," managing self doubt, sense of belonging, understanding myself, and questioning the need for formal diagnosis. Healthcare professionals must have an understanding of self-diagnosis to help individuals transition to formal diagnosis and to adequately educate, support, and screen this population for comorbidities. PMID- 27654241 TI - Effects of the Nursing Psychoeducation Program on the Acceptance of Medication and Condition-Specific Knowledge of Patients with Schizophrenia. AB - The objective of this study was to evaluate the clinical utility of the nursing psychoeducation program (NPE) for improving the acceptance of medication of inpatients with schizophrenia as well as their knowledge regarding their illness and the effects of medication on it. This study was a quasi-experimental study involving a convenience sample and was performed at the acute treatment units of two Japanese psychiatric hospitals. The subjects were recruited from among the inpatients being treated at the acute treatment units and were assigned to either the experimental or control group. The experimental group took part in the NPE, and the control group received the standard treatments for schizophrenia. Data were collected using structured questionnaires; i.e., the Medication Perception Scale for Patients with Schizophrenia (MPS), Drug Attitude Inventory-10 Questionnaire (DAI-10), and Knowledge of Illness and Drugs Inventory. Forty-three patients (13 men and 30 women) agreed in writing to participate in this study. During pre-/postintervention comparisons, the total MPS score, the 'efficacy of medication' subscale score, and the total DAI-10 score exhibited significant group*time interactions. PMID- 27654242 TI - Social Functioning and Self-Esteem of Substance Abuse Patients. AB - AIM: This descriptive study was conducted to examine the levels of social functioning and self-esteem in individuals diagnosed with substance abuse. MATERIAL AND METHOD: The study was conducted at the AMATEM (Alcohol and Substance Abuse Treatment Center) service of a psychiatry clinic in the Elazig province in eastern Turkey between September 1, 2014 and February 1, 2015. The population is comprised of 249 patients being treated in this clinic, and the sample included 203 patients who comply with the research criteria and agreed to participate in the study. A Socia-Demographic Questionnaire, Coopersmith Self-esteem Scale (CSI) and Social Functioning Scale (SFS) were used for data collection. Percentages, averages, standard deviations and Pearson's correlation were used for data analysis. RESULTS: This study found that the patients' mean sore on the Self esteem Scale is 50.97+/-18.01. Their score on the Social Functioning Scale is 115.76+/-22.41. A significant correlation between the patients' self-esteem and the age of first substance use was detected (p=0.001). A significant correlation was detected between their social functioning and the duration of their substance use (p<0.005). This study found a positive significant correlation between social functioning and self-esteem (p<0.001). CONCLUSION: This study found that substance abuse patients have a medium level of self-esteem and social functioning. A significant positive correlation between social functioning and self-esteem was found. It was also found that the age of first substance use and self-esteem are directly correlated. Counseling to increase patients' levels of self-esteem and improve their social functioning is recommended. PMID- 27654243 TI - Post-Traumatic Stress Disorder and It's Predictors Among Tibetan Adolescents 3Years After the High-Altitude Earthquake in China. AB - This study examined post-traumatic stress disorder(PTSD) and it's predictors among 4072 Tibetan adolescents 3years after the highaltitude earthquake. The instruments included The PTSD Checklist-Civilian version, The Internality, Powerful others, and Chance Scale and The Coping Style Scale. The results indicated the prevalence rate of probable PTSD was 17.8%.The predicting factors for PTSD were found to being aged 14 or older, being senior student, being monitor, being buried/injured, have family member died/amputated, have severer property loss, have witnessed death, have negative coping skills, and have power others locus of control. Effective mental health services should be developed to facilitate post-disaster recovery. PMID- 27654244 TI - Mothering a Child with Autism. PMID- 27654245 TI - Impact of Social Support on Symptoms of Depression and Loneliness in Survivors Bereaved by Suicide. AB - According to the latest statistics from the American Association of Suicidology, there were approximately 41,000 suicides in the United States, accounting for 112 suicides per day or one every 12.8minutes (Drapeau & McIntosh, 2015). Survivors bereaved by suicide often experience complicated grief and feelings of social isolation. The study was a secondary data analysis from a study which involved 44 participants over the age of 18 from Southwestern Pennsylvania. Symptoms of depression and loneliness were assessed in relation to reported social support available to participants. The findings support the notion that increased availability of support can decrease symptoms of depression. PMID- 27654247 TI - Psychological Distress and Violence Towards Parents of Patients with Schizophrenia. AB - The present study investigated the relationship between violence and psychological distress experienced by parents of patients with schizophrenia. Questionnaire data from 379 parents were analyzed. A total of 151 parents (39.8%) had not experienced violence in the past year, whereas 96 (25.3%) and 132 (34.8%) had experienced psychological violence only or physical violence, respectively. A total of 216 (57.0%) of parents reported being psychologically distressed. Multiple logistic regression revealed that the risk of psychological distress significantly increased with the experience of psychological and physical violence, lower household income, greater family stigma, and the increasing age of patients. PMID- 27654246 TI - Effects of Resourcefulness on Sleep Disturbances, Anxiety, and Depressive symptoms in Family Members of Intensive Care Unit Patients. AB - The study aimed to investigate the relationships among psychological distresses, resourcefulness, sleep disturbances, anxiety and depressive symptoms in family members of intensive care unit (ICU) patients. A cross-sectional, descriptive correlational design was employed. Using structural equation modeling (SEM) approach, relationships among factors, mediators, and outcomes were analyzed. The SEM explained 59% of the variances in depressive symptoms and 36% in anxiety. Family members with greater learned resourcefulness had fewer sleep disturbances, depressive and anxiety symptoms. Nursing professionals need to detect psychiatric disease of family members and must be especially vigilant with people who have low resourcefulness and sleep disturbances. PMID- 27654248 TI - Domestic Violence Against Women In Turkey: A Systematic Review And Meta Analysis. AB - AIM: This study was performed to determine the prevalence of and risk factors for domestic violence against women in Turkey. BACKGROUND: The data about domestic violence against women point out a serious problem all around the world along with including cultural differences. DESIGN: The prevalence of domestic violence against women was determined through a meta-analysis, and the risk factors were determined through a systematic review. A systematic search of eight electronic databases was conducted. In this study, 34 primary studies that were published between January 2000 and January 2015 were examined. RESULTS: The highest prevalence belonged to verbal violence followed by physical, emotional, economic, and sexual violence. Despite different questioning methods, it was determined that 22 risk factors were most commonly examined in the studies, and these risk factors were summed up under three separate categories: socio demographical characteristics, well-being related characteristics and marriage related characteristics. It is of further interest that the most commonly examined characteristics were socio demographic characteristics. CONCLUSION: Just as throughout the world, domestic violence is a common problem in Turkey. RELEVANCE TO CLINICAL PRACTICE: Nurses and midwives should focus not only on women's disorders but also on the difficulties the patient faces in regard to being a family. It presents valid evidence to produce policies on violence prevention. PMID- 27654249 TI - Black and Blue: Depression and African American Men. AB - Depression is a common mental disorder affecting individuals. Although many strides have been made in the area of depression, little is known about depression in special populations, especially African American men. African American men often differ in their presentation of depression and are often misdiagnosed. African American men are at greater risk for depression, but they are less likely to participate in mental health care. This article explores depression in African American by looking at environmental factors, sigma, role, and other unique to this populations, such as John Henryism. Interventions to encourage early screening and participation in care are also discussed. PMID- 27654250 TI - Adolescents' and Young Adults' Beliefs about Mental Health Services and Care: A Systematic Review. AB - BACKGROUND: Adolescents and young people are known to hold negative views about mental illness. There is less known about their beliefs about mental health services and care. OBJECTIVE: The aim of this study was to systematically examine literature on the beliefs of adolescents and young people from the general population about mental health services and care. Factors that positively and negatively influence these beliefs are also explored. METHODS: Relevant electronic databases were searched for papers published in the English language between January 2004 and October 2015. RESULTS: Culture seemed to influence how adolescents and young adults perceived mental health interventions. This was particularly evident in countries such as Palestine and South Africa where prayer was highly valued. Adolescents and young people were uninformed about psychiatric medication. They believed that accessing mental health care was a sign of weakness. Furthermore, they viewed psychiatric hospitals and various mental health professionals negatively. Film was found to have a negative impact on how adolescents and young people perceived mental health services, whereas open communication with family members was found to have a positive impact. CONCLUSION: Adolescents and young adults hold uninformed and stigmatizing beliefs about mental health treatments, mental health professionals, and access to care. The sources of these beliefs remain unclear although some at least seem influenced by culture. Further research, (particularly qualitative research) in this area is recommended in order to address current gaps in knowledge. PMID- 27654251 TI - Timing of Clinical Improvement in Assertive Community Treatment for Adolescents: A Pilot Naturalistic Observational Study. PMID- 27654252 TI - Determining Factors for the Unfolding Pathway of Peptides, Peptoids, and Peptidic Foldamers. AB - We present a study of the mechanical unfolding pathway of five different oligomers (alpha-peptide, beta-peptide, delta-aromatic-peptides, alpha/gamma peptides, and beta-peptoids), adopting stable helix conformations. Using force probe molecular dynamics, we identify the determining structural factors for the unfolding pathways and reveal the interplay between the hydrogen bond strength and the backbone rigidity in the stabilization of their helix conformations. On the basis of their behavior, we classify the oligomers in four groups and deduce a set of rules for the prediction of the unfolding pathways of small foldamers. PMID- 27654254 TI - Response to letter to Editor: "The clinical course of recurrent respiratory papillomatosis after the use of cidofovir is influenced by multiple factors" by Michel R. M. San Giorgi et al. PMID- 27654253 TI - Increased Plasma Dipeptidyl Peptidase-4 Activities in Patients with Coronary Artery Disease. AB - Dipeptidyl peptidase-4 (DPP4) is one of the most potent mammalian serine proteases participated in the pathogenesis of subclinical atherosclerosis. Here we investigated whether the plasma soluble form of DPP4 is associated with the prevalence of coronary artery disease (CAD) with and without diabetes mellitus (DM). A cross-sectional study was conducted of 496 aged 26-81 years with (n = 362) and without (n = 134) CAD. Plasma DPP4 activity, high sensitive C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein levels were measured. The coronary atherosclerotic plaques were evaluated by coronary angiography. The CAD patients with (n = 84) and without (n = 278) DM had significantly higher DPP4 levels (11.8 +/- 3.1 vs. 6.9 +/- 3.5 ng/mL, P<0.01) than the nonCAD subjects. The acute coronary syndrome patients (n = 299) had elevated DPP4 levels than those with stable angina patients (n = 83). CAD patients even without DM had increased plasma DPP4 activities as compared with nonCAD subjects (10.9 +/- 4.9 vs. 6.4 +/- 3.1, ng/L, P< 0.01). A linear regression analysis revealed that overall, the DPP4 levels were positively associated with LCL-C and hs-CRP levels as well as syntax scores. A multiple logistic regression analysis demonstrated that plasma DPP4 activity was independent predictor of CAD (odds ratio, 1.56; 95% CI, 1.19-1.73; P<0.01). Our study shows that increased DPP4 activity levels are associated with the presence of CAD and that the plasma DPP4 level serves as a novel biomarker for CAD even without DM. PMID- 27654255 TI - Adverse Event Profile by Folate Receptor Status for Vintafolide and Pegylated Liposomal Doxorubicin in Combination, Versus Pegylated Liposomal Doxorubicin Alone, in Platinum-Resistant Ovarian Cancer: Exploratory Analysis of the Phase II PRECEDENT Trial. AB - OBJECTIVE: This exploratory analysis evaluated the incidence of adverse events (AEs) by folate receptor (FR) status in the randomized, multicenter, open-label PRECEDENT study in women with platinum-resistant ovarian cancer receiving pegylated liposomal doxorubicin (PLD) +/- the small-molecule drug conjugate vintafolide. METHODS: Women 18 years or older with platinum-resistant ovarian cancer were randomized 2:1 to vintafolide (2.5 mg intravenously, 3 times per week, weeks 1 and 3, every 28 days) + PLD (50 mg/m intravenously, day 1, every 28 days) or PLD alone (same dose/schedule). The expression of functionally active FR was evaluated by single-photon emission computed tomography with etarfolatide. Patients were categorized according to FR positivity: patients with all target lesions positive for FR expression (FR 100%), patients with 1 or more but not all target lesions positive for FR expression (FR 10%-90%), and patients with all lesions negative for FR expression (FR 0%). RESULTS: Data on FR status were available for 94 patients: 38 were FR 100%, 36 were FR 10% to 90%, and 20 were FR 0%. Across all FR subgroups, the duration of treatment was longer, and the number of cycles was higher in combination-therapy arms than PLD-alone arms. Although the frequency of AEs was relatively consistent across subgroups, the FR 100% subgroup had a higher incidence of patients with at least 1 AE for combination therapy versus PLD alone. No surprising safety signals were shown according to FR status. The incidence of grade 3 or 4 treatment-emergent drug-related AEs was generally low across all FR subgroups and treatment arms. CONCLUSIONS: This exploratory analysis suggests that FR status does not influence the AE profile of vintafolide + PLD combination therapy or PLD alone in patients with platinum resistant ovarian cancer. Future a priori analyses in larger populations are needed to confirm these findings. PMID- 27654256 TI - Prognostic Significance of Cytokeratin 19 and Squamous Cell Cancer Antigen in Histologically Negative Sentinel Lymph Nodes of Cervical Squamous Cell Carcinoma. AB - OBJECTIVE: The aim of the study was to evaluate the prognostic value of positive cytokeratin 19 (CK19) and squamous cell cancer antigen (SCCAg) expression in histologically negative sentinel lymph nodes after surgery for cervical squamous cell carcinoma. METHODS: Immunohistochemistry was performed to detect the expression of CK19 and SCCAg using polyclonal antibody on 149 pair of formalin fixed, paraffin-embedded cervical squamous cell carcinoma and histologically negative sentinel lymph node tissue samples, and results were compared with data from the prospectively registry of cervical squamous cell carcinoma by univariate and multivariate logistic regression model focusing specifically on recurrence. The survival was assessed by the Kaplan-Meier method and proportional hazards model. RESULTS: Cytokeratin 19 and SCCAg expression in histologically negative sentinel lymph nodes were documented in 15.4% (n = 23) and 20.8% (n = 31) patients and were associated with a higher incidence of tumor progression and poorer disease-free survival (DFS, P < 0.05). Multivariate logistic regression analysis demonstrated that CK19 (P = 0.001) and SCCAg (P = 0.001) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.000), and cervical stroma infiltration depth (P = 0.005) were independent predictive factors for recurrence. The proportional hazards model identified CK19 (P = 0.001) and SCCAg (P = 0.005) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.003), and cervical stroma infiltration depth (P = 0.005), as independently related to DFS. Using subgroup analysis, we found that the CK19+/SCCAg + subgroup has the poorest prognosis, whereas the CK19-/SCCAg - subgroup has the best prognosis (P = 0.000). CONCLUSIONS: Immunohistochemical assessment of both CK19 and SCCAg status in histologically negative sentinel lymph nodes may be a valuable approach for predicting recurrence and survival after curative surgery for cervical squamous cell carcinoma. PMID- 27654257 TI - Dutch Risk Classification and FIGO 2000 for Gestational Trophoblastic Neoplasia Compared. AB - OBJECTIVE: Over the years, there has been a wide variety of classification systems in use worldwide to stratify patients between single-agent versus multi agent chemotherapy, hindering comparison of international research results. The study presents a retrospective comparison of the International Federation of Gynecology and Obstetrics 2000 and Dutch risk classification system for gestational trophoblastic neoplasia. METHODS AND MATERIALS: All patients diagnosed with gestational trophoblastic neoplasia between January 2003 and December 2012 at the trophoblastic disease centre in London were retrospectively scored according to the Dutch classification system (N = 813). RESULTS: An extensive overlap between both scoring systems was seen, even though items and relative value of items were quite distinct. The Dutch system seems to be simpler and easier to apply in all situation; a degree of overtreatment can however be presumed with the use of either system. CONCLUSIONS: Although it is likely that outcome is indeed affected by the individual factors used in both systems, many factors relate to tumor bulk and may not be independently prognostic. We therefore believe that further refinement of the classification systems and their underlying prognostic items plus any new items that seem promising would be useful. PMID- 27654258 TI - Predicting Model of Lymph Node Metastasis Using Preoperative Tumor Grade, Transvaginal Ultrasound, and Serum CA-125 Level in Patients With Endometrial Cancer. AB - OBJECTIVE: The purpose of this study was to evaluate the predicting model for lymph node metastasis using preoperative tumor grade, transvaginal sonography (TVS), and serum cancer antigen 125 (CA-125) level in patients with endometrial cancer. MATERIALS AND METHODS: Between January 2000 and February 2013, we identified 172 consecutive patients with surgically staged endometrial cancer. Transvaginal sonography was performed by an expert gynecologic radiologist in all patients. All patients had complete staging surgery including total hysterectomy with bilateral pelvic and para-aortic lymphadenectomy and were staged according to the 2009 International Federation of Gynecology and Obstetrics classification. Various clinicopathologic data were obtained from medical records and were retrospectively analyzed. RESULTS: Of 172 patients, 138 patients presented with stage I (118 IA and 20 IB), 12 had stage II, 18 had stage III (2 IIIA, 1 IIIB, 8 IIIC1, and 7 IIIC2), and 2 had stage IV diseases. Most patients had endometrioid adenocarcinoma (88.4%), and others (12.6%) had nonendometrioid histology. Eighteen patients (10.5%) were found to have lymph node metastasis. Deep myometrial invasion on preoperative TVS (>=50%), high serum CA-125 level (>= 35 IU/mL), preoperative grade 2 or 3 tumors were significant preoperative factors predicting lymph node metastasis. There was no significant association between preoperative histology and lymph node metastasis. We calculated the simple model predicting lymph node metastasis based on preoperative tumor grade, TVS findings, and CA-125 level using logistic regression analysis. The sensitivity and specificity of this model were 94% and 57%, respectively (area under the curve, 0.84; 95% confidence interval [CI], 0.74-0.93; P < 0.01). CONCLUSIONS: Preoperative tumor grade, myometrial invasion on preoperative TVS, and CA-125 can accurately predict lymph node metastasis in patients with endometrial cancer. The current study suggests the possibility that TVS could be positively used for preoperative evaluation strategy in the low-resource countries instead of expensive imaging modalities such as magnetic resonance imaging or positron emission tomography-computed tomography. PMID- 27654259 TI - Insulin-Like Growth Factor 1/Mammalian Target of Rapamycin and AMP-Activated Protein Kinase Signaling Involved in the Effects of Metformin in the Human Endometrial Cancer. AB - BACKGROUND: Metformin is a well-tolerated biguanide drug used for decades to treat type 2 diabetes mellitus. In recent years, long-term administration of metformin has been found to reduce carcinogenic risk for cancers derived from various tissues. However, its cellular and molecular mechanisms of anticancer action in the endometrial cancer (EC) have not yet been fully elucidated. PATIENTS AND METHODS: Sixty patients diagnosed as endometrial carcinoma were grouped into (n = 30) and non-treatment mixed (n = 30) for analysis. Thirty healthy donors are control groups. We attempt to investigate the interaction of metformin, insulin-like growth factor 1 (IGF-1) expression, and phosphorylated mammalian target of rapamycin (p-mTOR) and AMP-activated protein kinase (p-AMPK). RESULTS: We found that high IGF-1 plasma concentrations in women with EC were reversed by conventional antidiabetic doses of metformin in the present work. In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC. CONCLUSIONS: This pilot trial presents biological evidence consistent with antiproliferative effects of metformin in women with EC in the clinical setting. PMID- 27654260 TI - Effect of Physical Activity on Quality of Life as Perceived by Endometrial Cancer Survivors: A Systematic Review. AB - PURPOSE: A combination of the relatively high prevalence among gynecologic cancers, high survival, and the myriads of factors that negatively impact the quality of life (QoL) among endometrial cancer (EC) survivors underscores the potential benefits of meeting guideline physical activity (PA) guidelines of 150 minutes per week among EC survivors. The objective of the present systematic review was to collate and critically evaluate the currently available literature on the effects of PA on QoL among EC survivors. METHODS: Medline and Web of Science databases were searched for articles on EC, QoL, and PA. We also inspected bibliographies of relevant publications to identify related articles. Our search criteria yielded 70 studies, 7 of which met the inclusion criteria. RESULTS: Of the 7 studies examined, 2 of them were intervention studies, whereas 5 were cross-sectional studies. Meeting guideline PA was significantly associated with better QoL score in 4 of the 5 cross-sectional studies. CONCLUSIONS: Results from the cross-sectional studies suggest that EC survivors' inactivity is significantly correlated with poorer QoL. This correlation was worse among obese survivors compared with normal weight survivors. Endometrial cancer survivors may benefit from interventions that incorporate PA. More randomized intervention studies among EC survivors are needed to add to this body of evidence. PMID- 27654261 TI - Statin Use Significantly Improves Overall Survival in High-Grade Endometrial Cancer. AB - OBJECTIVE: Preclinical data and recent epidemiological studies suggest that statins have antiproliferative and antimetastatic effects in various cancer cells, and reduce cancer mortality and recurrence. We study the effect of statin use on survival outcomes and recurrence rates in patients with endometrial cancer with high-risk histology. MATERIALS AND METHODS: All patients receiving definitive therapy for high-risk endometrial cancer from 1995 to 2014 were retrospectively reviewed. Health characteristics at baseline were collected, and statin use was determined from medical records. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models were used for univariate and multivariate analysis to determine independent factors associated with OS and PFS. RESULTS: A total of 199 patients were included in the study, of which 76 were hyperlipidemic and 50 used statins. The median follow-up time was 31 months from time of diagnosis. Hyperlipidemic patients who used statins had improved OS compared with hyperlipidemic patients not using statins (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87; P = 0.02). Statin use was also associated with improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23-0.95; P = 0.04) on multivariate analysis. Hyperlipidemic patients who used statins had borderline improved freedom from local failure compared with hyperlipidemic cases not using statins (P = 0.08, log-rank test). Statin use was not found to be associated with improved cancer-specific mortality. CONCLUSIONS: Statin use is independently associated with significant improvements in PFS for the overall group and PFS and OS in the hyperlipidemic group. PMID- 27654262 TI - Long-Term Oncologic and Reproductive Outcomes in Young Women With Early Endometrial Cancer Conservatively Treated: A Prospective Study and Literature Update. AB - OBJECTIVE: This study aimed to analyze the long-term oncologic and reproductive outcomes in endometrial cancer (EC) in young patients conservatively treated by combined hysteroscopic resection (HR) and levonorgestrel intrauterine device (LNG IUD). METHODS: Twenty-one patients (age <= 40 years; Stage IA, G1-2 endometrioid EC), wishing to preserve their fertility, were enrolled into this prospective study. The HR was used to resect (1) the tumor lesion, (2) the endometrium adjacent to the tumor, and (3) the myometrium underlying the tumor. Hormonal therapy consisted of LNG-IUD (52 mg) for at least 6 months. RESULTS: The median follow-up time is 85 months (range, 30-114). After 3 months from the progestin start date, 18 patients (85.7%) showed a complete regression (CR), 2 (9.5%) showed persistent disease, whereas 1 patient (4.8%) presented with progressive disease and underwent definitive surgery (Stage IA, G3 endometrioid). At 6 months, 1 of the 2 persistences underwent definitive surgery (Stage IA, G1 endometrioid), whereas the other was successfully re-treated. Two recurrences (10.5%) were observed, both involving the endometrium and synchronous ovarian cancer (OC) (atypical hyperplasia and Stage IIB G1 endometrioid OC; Stage IA endometrioid G1 EC, and Stage IA G1 endometrioid OC). The median duration of complete response was 85 months (range, 8-117). Sixty-three percent of complete responders attempted to conceive with 92% and 83% pregnancy and live birth rates, respectively. To date, all patients are alive and have no evidence of disease. CONCLUSIONS: After a long follow-up, combined HR and LNG-IUD would seem to improve the efficacy of progestin alone. High pregnancy and live birth rates were observed in women attempting to conceive. This approach is still experimental and should be offered only in the framework of scientific protocols conducted in cancer centers. PMID- 27654263 TI - Impact of Abdominal Wall Metastases on Prognosis in Epithelial Ovarian Cancer. AB - OBJECTIVE: Epithelial ovarian cancer (EOC) patients with the presence of abdominal wall metastasis (AWM) are categorized as stage International Federation of Gynecology and Obstetrics (FIGO) IVB, irrespective of other biologic factors or preceding invasive intervention before final surgery. We evaluated the impact of AWM on patients' overall survival (OS). PATIENTS AND METHODS: In this exploratory study, 634 consecutive patients with advanced EOC treated in our center from 2000 to 2014 were included. Patients were categorized into FIGO IIIC (n = 308), FIGO IVB AWM only (n = 86), and FIGO IV others (metastases other than AWM, n = 240). Clinicopathological parameters and survival data were extracted from our prospectively maintained tumor registry. Survival analyses were calculated using Kaplan-Meier method and Cox regression models. RESULTS: In 75 (87.2%) of 86 cases, AWM was seen after a preceding intervention, and only in 12.7%, the deposits were spontaneously established. The median OS in patients with stage FIGO IIIC, FIGO IVB AWM only, and FIGO IV others was 37, 58, and 25 months (P < 0.001), respectively. Patients with FIGO IVB AWM only had a significantly better OS than patients with FIGO IV others (P < 0.001). The numeric longer OS of patients with FIGO IVB AWM only compared with patients with FIGO IIIC was not statistically significant (P = 0.151). In multivariate analysis considering all confounding factors including residual disease, OS of patients with FIGO IIIC did not differ from patients with FIGO AWM only (hazard ratio, 0.84; 95% confidence interval, 0.56-12.26; P = 0.398). CONCLUSIONS: Most AWM are acquired after preceding intervention (puncture or laparoscopy). Prognosis of patients with AWM as the only site of distant metastasis is superior compared with other stage FIGO IV patients. Therefore, up-staging of patients only because of AWM to FIGO IVB may be questioned. A revision/clarification of the FIGO classification system should be considered to avoid unnecessary stigmatization of patients and to classify these patients more appropriately according to prognosis. PMID- 27654264 TI - Valproic Acid as a Promising Co-Treatment With Paclitaxel and Doxorubicin in Different Ovarian Carcinoma Cell Lines. AB - OBJECTIVE: The current preferred treatment of ovarian cancer is combination chemotherapy, usually a platinum-based drug coupled with paclitaxel (PTX). Here, we investigated whether co-treatment with valproic acid (VPA) could increase the efficiency of various ovarian cancer drugs-PTX, doxorubicin (DOX), carboplatin (CBP), and cyclophosphamide (CP)-in different ovarian cancer cell lines. METHODS: Three different ovarian cancer cell lines (OVCAR-3, TOV-21G, and TOV-112D) were treated with chemotherapeutic drugs, alone or in combination with VPA. Cell viability (XTT assay), caspase-3 activity, and the expression of cell cycle- and apoptosis-related genes and proteins were assessed. Furthermore, the effects of these drugs on alpha-tubulin acetylation and DNA fragmentation were investigated. RESULTS: Paclitaxel and DOX decreased cell viability and increased caspase-3 activity, and co-treatment with VPA enhanced this effect. Carboplatin and CP had no effect. Responses to treatment with PAX and DOX together with VPA on gene expression profile were highly variable and depended on the cell line investigated. However, a common feature in all cell lines was an increased expression of CDKN1A, CCNE1, PARP1, and PARP3. Co-treatment with VPA enhanced the effect of DOX and PAX on most protein expressions investigated in TOV-21G and TOV 112D cell lines, whereas in OVCAR-3, the most effect was seen with DOX with VPA. Valproic acid did not increase PTX-induced alpha-tubulin acetylation. An additive effect of DOX with VPA on DNA fragmentation was observed in TOV-21G and TOV-112D cell lines but not in the OVCAR-3. CONCLUSIONS: Our results indicate that VPA could be a promising agent in combined anticancer therapy for ovarian cancer, with the combination of VPA and DOX being the most effective. Certainly, additional in vivo and ex vivo experiments are necessary to investigate the molecular mechanisms of action underlying the cellular effects reported here and to study possible clinically relevant effects in ovarian cancer explants. PMID- 27654265 TI - Central Nervous System Metastases in Patients With Cervical Carcinoma. AB - INTRODUCTION: Cervical cancer (CC) is the most common malignancy throughout developing countries, although considered rare, central nervous system metastasis (CNSm) does occur. OBJECTIVE: This study aimed to describe our experiences and compare them to other published cases. MATERIALS AND METHODS: From May 2009 to August 2015, the files of all patients with CC treated at our referral center were reviewed. RESULTS: We found 27 patients with CC and CNSm. Mean age at the time of CNS diagnosis was 50 +/- 11 years, mean interval between initial CC and CNSm was 46 months; the most frequent initial International Federation of Gynecology and Obstetrics stage was IIB with 17 patients followed by IB in 4. Fifty-nine percent of patients had lung metastases at the time CNSm were diagnosed. Headache was the most common symptom, followed by weakness, altered mental status, and ataxia/cerebellar. Mean survival was 8.2 months after CNSm was discovered; 3 patients are still alive. CONCLUSIONS: The present study describes the largest series of patients with CNSm from CC; this rare complication should be suspected in patients with CC who present with headache, ataxia, cranial nerve palsy, visual disturbance, altered mental status, focal weakness, or other neurological symptom, without other plausible explanation. PMID- 27654266 TI - Phase II Study Evaluating PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecologic Sarcomas and Mixed Epithelial-Mesenchymal Tumors A Phase II Protocol of the Arbeitsgemeinschaft Gynaekologische Onkologie Study Group (AGO-GYN 7). AB - BACKGROUND: Gynecologic sarcomas are rare diseases with still undefined optimal treatment. Platinum and anthracyclines were reported as active agents in gynecologic sarcoma and carcinosarcoma. So far, data regarding the combination of carboplatin and pegylated liposomal doxorubicin for this patient population are missing. METHODS: This prospective single-arm multicenter phase II trial evaluated the efficacy of carboplatin AUC 6 in combination with pegylated liposomal doxorubicin 40 mg/m q28 in 40 patients with newly diagnosed or recurrent gynecologic sarcoma or carcinosarcoma. RESULTS: Twenty patients with carcinosarcoma and 20 patients with leiomyosarcoma or endometrial stromal sarcoma were included. The percentage of patients with grade 3/4 neutropenia was 50%, but we did not observe any febrile neutropenia. The rates of grade 1 and 2 palmo plantar erythema were moderate with 25% and 10%, respectively. Response rate was 33.3%. The 12-month progression-free and overall survival times were 32.5% and 77.0%, respectively. CONCLUSIONS: The combination of carboplatin and pegylated liposomal doxorubicin is feasible and has activity within the investigated study cohort. PMID- 27654267 TI - Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis. AB - Long wavelength ultraviolet radiation (UVA, 320-400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA-protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions. PMID- 27654268 TI - Spatial Heterogeneity of Habitat Suitability for Rift Valley Fever Occurrence in Tanzania: An Ecological Niche Modelling Approach. AB - BACKGROUND: Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. MATERIALS AND METHODS: Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. PRINCIPAL FINDINGS: Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). CONCLUSION/SIGNIFICANCE: The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics. PMID- 27654272 TI - Help your patients downsize with bariatric surgery. AB - Your patient has probably tried everything else. Now she's chosen to have weight loss surgery. Do you know how to help her succeed? PMID- 27654273 TI - Help your patients downsize with bariatric surgery. PMID- 27654274 TI - Tighten your glycemic control. AB - Follow the development of a hyperglycemic insulin protocol for a cardiovascular surgical program. PMID- 27654269 TI - Combined Analysis of ChIP Sequencing and Gene Expression Dataset in Breast Cancer. AB - Breast cancer is a common malignancy in women and contribute largely to the cancer related death. The purpose of this study is to confirm the roles of GATA3 and identify potential biomarkers of breast cancer. Chromatin Immunoprecipitation combined with high-throughput sequencing (ChIP-Seq) (GSM1642515) and gene expression profiles (GSE24249) were downloaded from the Gene Expression Omnibus (GEO) database. Bowtie2 and MACS2 were used for the mapping and peak calling of the ChIP-Seq data respectively. ChIPseeker, a R bioconductor package was adopted for the annotation of the enriched peaks. For the gene expression profiles, we used affy and limma package to do normalization and differential expression analysis. The genes with fold change >2 and adjusted P-Value <0.05 were screened out. Besides, BETA (Binding and Expression Target Analysis) was used to do the combined analysis of ChIP-Seq and gene expression profiles. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for the functional enrichment analysis of overlapping genes between the target genes and differential expression genes (DEGs). What's more, the protein-protein interaction (PPI) network of the overlapping genes was obtained through the Human Protein Reference Database (HPRD). A total of 46,487 peaks were identified for GATA3 and out of which, 3256 ones were found to located at -3000 ~ 0 bp from the transcription start sites (TSS) of their nearby gene. A total of 236 down- and 343 up-regulated genes were screened out in GATA3 overexpression breast cancer samples compared with those in control. The combined analysis of ChIP-Seq and gene expression dataset showed GATA3 act as a repressor in breast cancer. Besides, 68 overlaps were obtained between the DEGs and genes included in peaks located at -3000 ~ 0 bp from TSS. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cancer progression and gene regulation were found to be enriched in those overlaps. In the PPI network, NDRG1, JUP and etc. were found to directly interact with large number of genes, which might indicate their important roles in the progression of breast cancer. PMID- 27654275 TI - Preventing venous thromboembolism. AB - Learn to recognize who's at risk for potentially fatal complications and how to reduce your patient's risks. PMID- 27654276 TI - Extreme makeover-OR edition. AB - With an eye toward becoming a center for orthopedic excellence, one hospital's surgical-services team took the helm of redeveloping the facility's surgical suite. PMID- 27654277 TI - Slash sharps risk for surgical personnel. AB - Injury patterns for OR staff members differ from those in other healthcare settings. For this reason, tailor safety strategies to the OR environment to reduce injuries and blood exposures in this setting. PMID- 27654278 TI - Association of Peripheral Blood Levels of Brain-Derived Neurotrophic Factor With Autism Spectrum Disorder in Children: A Systematic Review and Meta-analysis. AB - Importance: Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) may be implicated in the developmental outcomes of children with autism spectrum disorder (ASD). Objective: To use meta-analysis to determine whether children with ASD have altered peripheral blood levels of BDNF. Data Source: A systematic search of PubMed, PsycINFO, and Web of Science was performed for English-language literature through February 7, 2016. The search terms included brain-derived neurotrophic factor or BDNF in combination with autism, without year restriction. Two additional records were retrieved after a review of the reference lists of selected articles. Study Selection: Studies were included if they provided data on peripheral blood levels of BDNF in children with ASD and healthy control children. Studies that included adults or with overlapping samples were excluded. Data Extraction and Synthesis: Data were extracted by 2 independent observers from 19 included studies. Data were pooled using a random effects model with Comprehensive Meta-analysis software. Main Outcomes and Measures: Blood levels of BDNF in children with ASD compared with healthy controls. Altered levels of BDNF were hypothesized to be related to ASD. Results: This meta-analysis included 19 studies with 2896 unique participants. Random effects meta-analysis of all 19 studies showed that children with ASD had significantly increased peripheral blood levels of BDNF compared with healthy controls (Hedges g, 0.490; 95% CI, 0.185-0.794; P = .002). Subgroup analyses in 4 studies revealed that neonates diagnosed with ASD later in life had no association with blood levels of BDNF (Hedges g, 0.384; 95% CI, -0.244 to 1.011; P = .23), whereas children in the nonneonate ASD group (15 studies) demonstrated significantly increased BDNF levels compared with healthy controls (Hedges g, 0.524; 95% CI, 0.206 to 0.842; P = .001). Further analysis showed that children in the nonneonate ASD group had increased BDNF levels in serum (10 studies) (Hedges g, 0.564; 95% CI, 0.168 to 0.960; P = .005) but not in plasma (5 studies) (Hedges g, 0.436; 95% CI, -0.176 to 1.048; P = .16). Meta-regression analyses revealed that sample size had a moderating effect on the outcome of the meta analysis in the nonneonate group. In addition, no publication bias was found in the meta-analysis. Conclusions and Relevance: Children with ASD have increased peripheral blood levels of BDNF, strengthening the clinical evidence of an abnormal neurotrophic factor profile in this population. PMID- 27654279 TI - Characteristics of Plasmonic Bragg Reflectors with Graphene-Based Silicon Grating. AB - We propose a plasmonic Bragg reflector (PBR) composed of a single-layer graphene based silicon grating and numerically study its performance. An external voltage gating has been applied to graphene to tune its optical conductivity. It is demonstrated that SPP modes on graphene exhibit a stopband around the Bragg wavelengths. By introducing a nano-cavity into the PBR, a defect resonance mode is formed inside the stopband. We further design multi-defect PBR to adjust the characteristics of transmission spectrum. In addition, through patterning the PBR unit into multi-step structure, we lower the insertion loss and suppress the rippling in transmission spectra. The finite element method (FEM) has been utilized to perform the simulation work. PMID- 27654280 TI - High-Performance Self-powered Photodetectors Based on ZnO/ZnS Core-Shell Nanorod Arrays. AB - In recent years, there is an urgent demand for high-performance ultraviolet photodetectors with high photosensitivity, fast responsivity, and excellent spectral selectivity. In this letter, we report a self-powered photoelectrochemical cell-type UV detector using the ZnO/ZnS core-shell nanorod array as the active photoanode and deionized water as the electrolyte. This photodetector demonstrates an excellent spectral selectivity and a rapid photoresponse time of about 0.04 s. And the maximum responsivity is more than 0.056 (A/W) at 340 nm, which shows an improvement of 180 % compared to detectors based on the bare ZnO nanorods. This improved photoresponsivity can be understood from the step-like band energy alignment of the ZnO/ZnS interface, which will accelerate the separation of photoexcited electron-hole pairs and improve the efficiency of the photodetector. Considering its uncomplicated low-cost fabrication process, and environment-friendly feature, this self-powered device is a promising candidate for UV detector application. PMID- 27654281 TI - Plasmonic Probe With Circular Nano-Moat for far-Field Free Nanofocusing. AB - In this work, a metallic probe with a sharp tip and two half-circular nanostructures on its base is introduced and investigated. The proposed design aims at improving the detection performance of a probe for scattering scanning near-field optical microscopy in terms of enhanced signal-to-noise ratio. Under the premise of processing feasibility, the structure of the probe is designed and optimized with three-dimensional finite-difference time-domain method. And then the performance and optical property of the probe are theoretically investigated and experimentally demonstrated using a scanning near-field optical microscope with aperture probe. It is indicated that a tightly confined optical field with significantly reduced far-field background can be achieved at the tip apex of the probe. PMID- 27654282 TI - Potential of the Antibody Against cis-Phosphorylated Tau in the Early Diagnosis, Treatment, and Prevention of Alzheimer Disease and Brain Injury. AB - Alzheimer disease (AD) and chronic traumatic encephalopathy (CTE) share a common neuropathologic signature-neurofibrillary tangles made of phosphorylated tau-but do not have the same pathogenesis or symptoms. Although whether traumatic brain injury (TBI) could cause AD has not been established, CTE is shown to be associated with TBI. Until recently, whether and how TBI leads to tau-mediated neurodegeneration was unknown. The unique prolyl isomerase Pin1 protects against the development of tau-mediated neurodegeneration in AD by converting the phosphorylated Thr231-Pro motif in tau (ptau) from the pathogenic cis conformation to the physiologic trans conformation, thereby restoring ptau function. The recent development of antibodies able to distinguish and eliminate both conformations specifically has led to the discovery of cis-ptau as a precursor of tau-induced pathologic change and an early driver of neurodegeneration that directly links TBI to CTE and possibly to AD. Within hours of TBI in mice or neuronal stress in vitro, neurons prominently produce cis-ptau, which causes and spreads cis-ptau pathologic changes, termed cistauosis. Cistauosis eventually leads to widespread tau-mediated neurodegeneration and brain atrophy. Cistauosis is effectively blocked by the cis-ptau antibody, which targets intracellular cis-ptau for proteasome-mediated degradation and prevents extracellular cis-ptau from spreading to other neurons. Treating TBI mice with cis-ptau antibody not only blocks early cistauosis but also prevents development and spreading of tau-mediated neurodegeneration and brain atrophy and restores brain histopathologic features and functional outcomes. Thus, cistauosis is a common early disease mechanism for AD, TBI, and CTE, and cis-ptau and its antibody may be useful for early diagnosis, treatment, and prevention of these devastating diseases. PMID- 27654283 TI - Simultaneous transapical transcatheter mitral and aortic valve replacement for native valve stenosis. PMID- 27654284 TI - Early Secretory Antigenic Target-6 Drives Matrix Metalloproteinase-10 Gene Expression and Secretion in Tuberculosis. AB - Tuberculosis (TB) causes disease worldwide, and multidrug resistance is an increasing problem. Matrix metalloproteinases (MMPs), particularly the collagenase MMP-1, cause lung extracellular matrix destruction, which drives disease transmission and morbidity. The role in such tissue damage of the stromelysin MMP-10, a key activator of the collagenase MMP-1, was investigated in direct Mycobacterium tuberculosis (Mtb)-infected macrophages and in conditioned medium from Mtb-infected monocyte-stimulated cells. Mtb infection increased MMP 10 secretion from primary human macrophages 29-fold, whereas Mtb-infected monocytes increased secretion by 4.5-fold from pulmonary epithelial cells and 10.5-fold from fibroblasts. Inhibition of MMP-10 activity decreased collagen breakdown. In two independent cohorts of patients with TB from different continents, MMP-10 was increased in both induced sputum and bronchoalveolar lavage fluid compared with control subjects and patients with other respiratory diseases (both P < 0.05). Mtb drove 3.5-fold greater MMP-10 secretion from human macrophages than the vaccine strain bacillus Calmette-Guerin (P < 0.001), whereas both mycobacteria up-regulated TNF-alpha secretion equally. Using overlapping, short, linear peptides covering the sequence of early secretory antigenic target 6, a virulence factor secreted by Mtb, but not bacillus Calmette-Guerin, we found that stimulation of human macrophages with a single specific 15-amino acid peptide sequence drove threefold greater MMP-10 secretion than any other peptide (P < 0.001). Mtb-driven MMP-10 secretion was inhibited in a dose-dependent manner by p38 and extracellular signal-related kinase mitogen-activated protein kinase blockade (P < 0.001 and P < 0.01 respectively), but it was not affected by inhibition of NF-kappaB. In summary, Mtb activates inflammatory and stromal cells to secrete MMP-10, and this is partly driven by the virulence factor early secretory antigenic target-6, implicating it in TB-associated tissue destruction. PMID- 27654285 TI - Influenza Virus Susceptibility of Wild-Derived CAST/EiJ Mice Results from Two Amino Acid Changes in the MX1 Restriction Factor. AB - : The interferon-regulated Mx1 gene of the A2G mouse strain confers a high degree of resistance against influenza A and Thogoto viruses. Most other laboratory inbred mouse strains carry truncated nonfunctional Mx1 alleles and, consequently, exhibit high virus susceptibility. Interestingly, CAST/EiJ mice, derived from wild Mus musculus castaneus, possess a seemingly intact Mx1 gene but are highly susceptible to influenza A virus challenge. To determine whether the enhanced influenza virus susceptibility is due to intrinsically reduced antiviral activity of the CAST-derived Mx1 allele, we generated a congenic C57BL/6J mouse line that carries the Mx locus of CAST/EiJ mice. Adult animals of this line were almost as susceptible to influenza virus challenge as standard C57BL/6J mice lacking functional Mx1 alleles but exhibited far more pronounced resistance to Thogoto virus. Sequencing revealed that CAST-derived MX1 differs from A2G-derived MX1 by two amino acids (G83R and A222V) in the GTPase domain. Especially the A222V mutation reduced GTPase activity of purified MX1 and diminished the inhibitory effect of MX1 in influenza A virus polymerase activity assays. Further, MX1 protein was substantially less abundant in organs of interferon-treated mice carrying the CAST Mx1 allele than in those of mice carrying the A2G Mx1 allele. We found that the CAST-specific mutations reduced the metabolic stability of the MX1 protein although Mx1 mRNA levels were unchanged. Thus, the enhanced influenza virus susceptibility of CAST/EiJ mice can be explained by minor alterations in the MX1 restriction factor that negatively affect its enzymatic activity and reduce its half-life. IMPORTANCE: Although the crystal structure of the prototypic human MXA protein is known, the importance of specific protein domains for antiviral activity is still incompletely understood. Novel insights might come from studying naturally occurring MX protein variants with altered antiviral activity. Here we identified two seemingly minor amino acid changes in the GTPase domain that negatively affect the enzymatic activity and metabolic stability of murine MX1 and thus dramatically reduce the influenza virus resistance of the respective mouse inbred strain. These observations highlight our current inability to predict the biological consequences of previously uncharacterized MX mutations in mice. Since this is probably also true for naturally occurring mutations in Mx genes of humans, careful experimental analysis of any natural MXA variants for altered activity is necessary in order to assess possible consequences of such mutations on innate antiviral immunity. PMID- 27654286 TI - The Glycosylphosphatidylinositol-Anchored Variable Region of Llama Heavy Chain Only Antibody JM4 Efficiently Blocks both Cell-Free and T Cell-T Cell Transmission of Human Immunodeficiency Virus Type 1. AB - : The variable regions (VHHs) of two heavy chain-only antibodies, JM2 and JM4, from llamas that have been immunized with a trimeric gp140 bound to a CD4 mimic have been recently isolated (here referred to as VHH JM2 and VHH JM4, respectively). JM2 binds the CD4-binding site of gp120 and neutralizes HIV-1 strains from subtypes B, C, and G. JM4 binds gp120 and neutralizes HIV-1 strains from subtypes A, B, C, A/E, and G in a CD4-dependent manner. In the present study, we constructed glycosylphosphatidylinositol (GPI)-anchored VHH JM2 and JM4 along with an E4 control and transduced them into human CD4+ cell lines and primary CD4 T cells. We report that by genetically linking the VHHs with a GPI attachment signal, VHHs are targeted to the lipid rafts of the plasma membranes. Expression of GPI-VHH JM4, but not GPI-VHH E4 and JM2, on the surface of transduced TZM.bl cells potently neutralizes multiple subtypes of HIV-1 isolates, including tier 2 or 3 strains, transmitted founders, quasispecies, and soluble single domain antibody (sdAb) JM4-resistant viruses. Moreover, transduction of CEMss-CCR5 cells with GPI-VHH JM4, but not with GPI-VHH E4, confers resistance to both cell-free and T cell-T cell transmission of HIV-1 and HIV-1 envelope mediated fusion. Finally, GPI-VHH JM4-transduced human primary CD4 T cells efficiently resist both cell-free and T cell-T cell transmission of HIV-1. Thus, we conclude that VHH JM4, when targeted to the lipid rafts of the plasma membrane, efficiently neutralizes HIV-1 infection via both cell-free and T cell-T cell transmission. Our findings should have important implications for GPI anchored antibody-based therapy against HIV-1. IMPORTANCE: Lipid rafts are specialized dynamic microdomains of the plasma membrane and have been shown to be gateways for HIV-1 budding as well as entry into T cells and macrophages. In nature, many glycosylphosphatidylinositol (GPI)-anchored proteins localize in the lipid rafts. In the present study, we developed GPI-anchored variable regions (VHHs) of two heavy chain-only antibodies, JM2 and JM4, from immunized llamas. We show that by genetically linking the VHHs with a GPI attachment signal, VHHs are targeted to the lipid rafts of the plasma membranes. GPI-VHH JM4, but not GPI-VHH JM2, in transduced CD4+ cell lines and human primary CD4 T cells not only efficiently blocks diverse HIV-1 strains, including tier 2 or 3 strains, transmitted founders, quasispecies, and soluble sdAb JM4-resistant strains, but also efficiently interferes T cell-T cell transmissions of HIV-1 and HIV-1 envelope-mediated fusion. Our findings should have important implications in GPI anchored antibody-based therapy against HIV-1. PMID- 27654287 TI - Tetherin Antagonism by HIV-1 Group M Nef Proteins. AB - : Although Nef is the viral gene product used by most simian immunodeficiency viruses to overcome restriction by tetherin, this activity was acquired by the Vpu protein of HIV-1 group M viruses due to the absence of sequences in human tetherin that confer susceptibility to Nef. Thus, it is widely accepted that HIV 1 group M uses Vpu instead of Nef to counteract tetherin. Challenging this paradigm, we identified Nef alleles of HIV-1 group M isolates with significant activity against human tetherin. These Nef proteins promoted virus release and tetherin downmodulation from the cell surface, and in the context of vpu-deleted HIV-1 recombinants, enhanced virus replication and resistance to antibody dependent cell-mediated cytotoxicity (ADCC). Further analysis revealed that the Vpu proteins from several of these viruses lack anti-tetherin activity, suggesting that under certain circumstances, HIV-1 group M Nef may acquire the ability to counteract tetherin to compensate for the loss of this function by Vpu. These observations illustrate the remarkable plasticity of HIV-1 in overcoming restriction by tetherin and challenge the prevailing view that all HIV 1 group M isolates use Vpu to counteract tetherin. IMPORTANCE: Most HIV-1 group M viruses, the main group of HIV-1 responsible for the global AIDS pandemic, use their Vpu proteins to overcome restriction by tetherin (BST-2 or CD317), which is a transmembrane protein that inhibits virus release from infected cells. Here we show that the Nef proteins of certain HIV-1 group M isolates can acquire the ability to counteract tetherin. These results challenge the current paradigm that HIV-1 group M exclusively uses Vpu to counteract tetherin and underscore the importance of tetherin antagonism for efficient viral replication. PMID- 27654288 TI - Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV 1 Envelope Glycoprotein and Display a Preference for Quaternary Binding. AB - : One of the goals of HIV-1 vaccine development is the elicitation of neutralizing antibodies against vulnerable regions on the envelope glycoprotein (Env) viral spike. Broadly neutralizing antibodies targeting the Env glycan-V3 region (also called the N332 glycan supersite) have been described previously, with several single lineages each derived from different individual donors. We used a high-throughput B-cell culture method to isolate neutralizing antibodies from an HIV-1-infected donor with high serum neutralization breadth. Clonal relatives from three distinct antibody lineages were isolated. Each of these antibody lineages displayed modest breadth and potency but shared several characteristics with the well-characterized glycan-V3 antibodies, including dependence on glycans N332 and N301, VH4 family gene utilization, a heavy chain complementarity-determining region 2 (CDRH2) insertion, and a longer-than-average CDRH3. In contrast to previously described glycan-V3 antibodies, these antibodies preferentially recognized the native Env trimer compared to monomeric gp120. These data indicate the diversity of antibody specificities that target the glycan-V3 site. The quaternary binding preference of these antibodies suggests that that their elicitation likely requires the presentation of a native-like trimeric Env immunogen. IMPORTANCE: Broadly neutralizing antibodies targeting the HIV-1 glycan-V3 region with single lineages from individual donors have been described previously. Here we describe three lineages from a single donor, each of which targets glycan-V3. Unlike previously described glycan-V3 antibodies, these mature antibodies bind preferentially to the native Env trimer and weakly to the gp120 monomer. These data extend our knowledge of the immune response recognition of the N332 supersite region and suggest that the mode of epitope recognition is more complex than previously anticipated. PMID- 27654289 TI - The P Protein of Spring Viremia of Carp Virus Negatively Regulates the Fish Interferon Response by Inhibiting the Kinase Activity of TANK-Binding Kinase 1. AB - : Spring viremia of carp virus (SVCV) is an efficient pathogen causing high mortality in the common carp. Fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral response; therefore, the strategies that SVCV uses to avoid the cellular IFN response were investigated. Here, we report that the SVCV P protein is phosphorylated by cellular TANK-binding kinase 1 (TBK1), which decreases IFN regulatory factor 3 (IRF3) phosphorylation and suppresses IFN production. First, overexpression of P protein inhibited the IFN promoter activation induced by SVCV and the IFN activity activated by the mitochondrial antiviral signaling protein (MAVS) although TBK1 activity was not blocked by P protein. Second, P protein colocalized and interacted with TBK1. Dominant negative experiments suggested that the TBK1 N-terminal kinase domain interacted with P protein and was essential for P protein and IRF3 phosphorylation. Finally, P protein overexpression reduced the IRF3 phosphorylation activated by TBK1 and reduced host cellular ifn transcription. Collectively, our data demonstrated that the SVCV P protein is a decoy substrate for the host phosphokinase TBK1, preventing IFN production and facilitating SVCV replication. IMPORTANCE: TBK1 is a pivotal phosphokinase that activates host IFN production to defend against viral infection; thus, it is a potential target for viruses to negatively regulate IFN response and facilitate viral evasion. We report that the SVCV P protein functions as a decoy substrate for cellular TBK1, leading to the reduction of IRF3 phosphorylation and suppression of IFN expression. These findings reveal a novel immune evasion mechanism of SVCV. PMID- 27654290 TI - Multiple Strategies Reveal a Bidentate Interaction between the Nipah Virus Attachment and Fusion Glycoproteins. AB - : The paramyxoviral family contains many medically important viruses, including measles virus, mumps virus, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and the deadly zoonotic henipaviruses Hendra and Nipah virus (NiV). To both enter host cells and spread from cell to cell within infected hosts, the vast majority of paramyxoviruses utilize two viral envelope glycoproteins: the attachment glycoprotein (G, H, or hemagglutinin-neuraminidase [HN]) and the fusion glycoprotein (F). Binding of G/H/HN to a host cell receptor triggers structural changes in G/H/HN that in turn trigger F to undergo a series of conformational changes that result in virus-cell (viral entry) or cell-cell (syncytium formation) membrane fusion. The actual regions of G/H/HN and F that interact during the membrane fusion process remain relatively unknown though it is generally thought that the paramyxoviral G/H/HN stalk region interacts with the F head region. Studies to determine such interactive regions have relied heavily on coimmunoprecipitation approaches, whose limitations include the use of detergents and the micelle-mediated association of proteins. Here, we developed a flow-cytometric strategy capable of detecting membrane protein-protein interactions by interchangeably using the full-length form of G and a soluble form of F, or vice versa. Using both coimmunoprecipitation and flow-cytometric strategies, we found a bidentate interaction between NiV G and F, where both the stalk and head regions of NiV G interact with F. This is a new structural biological finding for the paramyxoviruses. Additionally, our studies disclosed regions of the NiV G and F glycoproteins dispensable for the G and F interactions. IMPORTANCE: Nipah virus (NiV) is a zoonotic paramyxovirus that causes high mortality rates in humans, with no approved treatment or vaccine available for human use. Viral entry into host cells relies on two viral envelope glycoproteins: the attachment (G) and fusion (F) glycoproteins. Binding of G to the ephrinB2 or ephrinB3 cell receptors triggers conformational changes in G that in turn cause F to undergo conformational changes that result in virus-host cell membrane fusion and viral entry. It is currently unknown, however, which specific regions of G and F interact during membrane fusion. Past efforts to determine the interacting regions have relied mainly on coimmunoprecipitation, a technique with some pitfalls. We developed a flow-cytometric assay to study membrane protein protein interactions, and using this assay we report a bidentate interaction whereby both the head and stalk regions of NiV G interact with NiV F, a new finding for the paramyxovirus family. PMID- 27654291 TI - Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission. AB - : Multiple novel members of the genus Hepacivirus have recently been discovered in diverse mammalian species. However, to date, their replication mechanisms and zoonotic potential have not been explored in detail. The NS3/4A serine protease of hepatitis C virus (HCV) is critical for cleavage of the viral polyprotein. It also cleaves the cellular innate immune adaptor MAVS, thus decreasing interferon (IFN) production and contributing to HCV persistence in the human host. To investigate the conservation of fundamental aspects of the hepaciviral life cycle, we explored if MAVS cleavage and suppression of innate immune signaling represent a common mechanism employed across different clades of the genus Hepacivirus to enhance viral replication. To estimate the zoonotic potential of these nonhuman hepaciviruses, we assessed if their NS3/4A proteases were capable of cleaving human MAVS. NS3/4A proteases of viruses infecting colobus monkeys, rodents, horses, and cows cleaved the MAVS proteins of their cognate hosts and interfered with the ability of MAVS to induce the IFN-beta promoter. All NS3/4A proteases from nonhuman viruses readily cleaved human MAVS. Thus, NS3/4A dependent cleavage of MAVS is a conserved replication strategy across multiple clades within the genus Hepacivirus Human MAVS is susceptible to cleavage by these nonhuman viral proteases, indicating that it does not pose a barrier for zoonotic transmission of these viruses to humans. IMPORTANCE: Virus infection is recognized by cellular sensor proteins triggering innate immune signaling and antiviral defenses. While viruses have evolved strategies to thwart these antiviral programs in their cognate host species, these evasion mechanisms are often ineffective in a novel host, thus limiting viral transmission across species. HCV, the best-characterized member of the genus Hepacivirus within the family Flaviviridae, uses its NS3/4A protease to disrupt innate immune signaling by cleaving the cellular adaptor protein MAVS. Recently, a large number of HCV related viruses have been discovered in various animal species, including wild, livestock, and companion animals. We show that the NS3/4A proteases of these hepaciviruses from different animals and representing various clades of the genus cleave their cognate host MAVS proteins in addition to human MAVS. Therefore, cleavage of MAVS is a common strategy of hepaciviruses, and human MAVS is likely unable to limit replication of these nonhuman viruses upon zoonotic exposure. PMID- 27654292 TI - Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication. AB - : Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse side effects, including nephrotoxicity and hematological toxicity. Thus, there is a medical need for safer and more effective CMV therapeutics. Using a high-content screen, we identified the cardiac glycoside convallatoxin as an effective compound that inhibits CMV infection. Using a panel of cardiac glycoside variants, we assessed the structural elements critical for anti-CMV activity by both experimental and in silico methods. Analysis of the antiviral effects, toxicities, and pharmacodynamics of different variants of cardiac glycosides identified the mechanism of inhibition as reduction of methionine import, leading to decreased immediate-early gene translation without significant toxicity. Also, convallatoxin was found to dramatically reduce the proliferation of clinical CMV strains, implying that its mechanism of action is an effective strategy to block CMV dissemination. Our study has uncovered the mechanism and structural elements of convallatoxin, which are important for effectively inhibiting CMV infection by targeting the expression of immediate early genes. IMPORTANCE: Cytomegalovirus is a highly prevalent virus capable of causing severe disease in certain populations. The current FDA-approved therapeutics all target the same stage of the viral life cycle and induce toxicity and viral resistance. We identified convallatoxin, a novel cell targeting antiviral that inhibits CMV infection by decreasing the synthesis of viral proteins. At doses low enough for cells to tolerate, convallatoxin was able to inhibit primary isolates of CMV, including those resistant to the anti-CMV drug ganciclovir. In addition to identifying convallatoxin as a novel antiviral, limiting mRNA translation has a dramatic impact on CMV infection and proliferation. PMID- 27654293 TI - Resistance to Mutant Group 2 Influenza Virus Neuraminidases of an Oseltamivir Zanamivir Hybrid Inhibitor. AB - : Influenza virus neuraminidase (NA) drug resistance is one of the challenges to preparedness against epidemic and pandemic influenza virus infections. NA N1- and N2-containing influenza viruses are the primary cause of seasonal epidemics and past pandemics. The structural and functional basis underlying drug resistance of the influenza virus N1 NA is well characterized. Yet drug resistance of the N2 strain is not well understood. Here, we confirm that replacement of N2 E119 or I222 results in multidrug resistance, and when the replacements occur together, the sensitivity to NA inhibitors (NAI) is reduced severely. Using crystallographic studies, we showed that E119 replacement results in a loss of hydrogen bonding to oseltamivir and zanamivir, whereas I222 replacement results in a change in the hydrophobic environment that is critical for oseltamivir binding. Moreover, we found that MS-257, a zanamivir-oseltamivir hybrid inhibitor, is less susceptible to drug resistance. The binding mode of MS-257 shows that increased hydrogen bonding interactions between the inhibitor and NA active site anchor the inhibitor within the active site and allow adjustments in response to active-site modifications. Such stability is likely responsible for the observed reduced susceptibility to drug resistance. MS-257 serves as a next generation anti-influenza virus drug candidate and serves also as a scaffold for further design of NAIs. IMPORTANCE: Oseltamivir and zanamivir are the two major antiviral drugs available for the treatment of influenza virus infections. However, multidrug-resistant viruses have emerged in clinical cases, which pose a challenge for the development of new drugs. N1 and N2 subtypes exist in the viruses which cause seasonal epidemics and past pandemics. Although N1 drug resistance is well characterized, the molecular mechanisms underlying N2 drug resistance are unknown. A previous report showed that an N2 E119V/I222L dual mutant conferred drug resistance to seasonal influenza virus. Here, we confirm that these substitutions result in multidrug resistance and dramatically reduced sensitivity to NAI. We further elucidate the molecular mechanism underlying N2 drug resistance by solving crystal structures of the N2 E119V and I222L mutants and the dual mutant. Most importantly, we found that a novel oseltamivir zanamivir hybrid inhibitor, MS-257, remains more effective against drug-resistant N2 and is a promising candidate as a next-generation anti-influenza virus drug. PMID- 27654294 TI - The Cytoskeletal Adaptor Obscurin-Like 1 Interacts with the Human Papillomavirus 16 (HPV16) Capsid Protein L2 and Is Required for HPV16 Endocytosis. AB - : The human papillomavirus (HPV) capsid protein L2 is essential for viral entry. To gain a deeper understanding of the role of L2, we searched for novel cellular L2-interacting proteins. A yeast two-hybrid analysis uncovered the actin depolymerizing factor gelsolin, the membrane glycoprotein dysadherin, the centrosomal protein 68 (Cep68), and the cytoskeletal adaptor protein obscurin like 1 protein (OBSL1) as putative L2 binding molecules. Pseudovirus (PsV) infection assays identified OBSL1 as a host factor required for gene transduction by three oncogenic human papillomavirus types, HPV16, HPV18, and HPV31. In addition, we detected OBSL1 expression in cervical tissue sections and noted the involvement of OBSL1 during gene transduction of primary keratinocytes by HPV16 PsV. Complex formation of HPV16 L2 with OBSL1 was demonstrated in coimmunofluorescence and coimmunoprecipitation studies after overexpression of L2 or after PsV exposure. We observed a strong colocalization of OBSL1 with HPV16 PsV and tetraspanin CD151 at the plasma membrane, suggesting a role for OBSL1 in viral endocytosis. Indeed, viral entry assays exhibited a reduction of viral endocytosis in OBSL1-depleted cells. Our results suggest OBSL1 as a novel L2 interacting protein and endocytosis factor in HPV infection. IMPORTANCE: Human papillomaviruses infect mucosal and cutaneous epithelia, and the high-risk HPV types account for 5% of cancer cases worldwide. As recently discovered, HPV entry occurs by a clathrin-, caveolin-, and dynamin-independent endocytosis via tetraspanin-enriched microdomains. At present, the cellular proteins involved in the underlying mechanism of this type of endocytosis are under investigation. In this study, the cytoskeletal adaptor OBSL1 was discovered as a previously unrecognized interaction partner of the minor capsid protein L2 and was identified as a proviral host factor required for HPV16 endocytosis into target cells. The findings of this study advance the understanding of a so far less well characterized endocytic pathway that is used by oncogenic HPV subtypes. PMID- 27654296 TI - Extragenic Suppression of a Mutation in Herpes Simplex Virus 1 UL34 That Affects Lamina Disruption and Nuclear Egress. AB - : Nuclear egress of herpesviruses is accompanied by changes in the architecture of the nuclear membrane and nuclear lamina that are thought to facilitate capsid access to the inner nuclear membrane (INM) and curvature of patches of the INM around the capsid during budding. Here we report the properties of a point mutant of pUL34 (Q163A) that fails to induce gross changes in nuclear architecture or redistribution of lamin A/C. The UL34(Q163A) mutant shows a roughly 100-fold defect in single-step growth, and it forms small plaques. This mutant has a defect in nuclear egress, and furthermore, it fails to disrupt nuclear shape or cause observable displacement of lamin A/C despite retaining the ability to recruit the pUS3 and PKC protein kinases and to mediate phosphorylation of emerin. Extragenic suppressors of the UL34(Q163A) phenotype were isolated, and all of them carry a single mutation of arginine 229 to leucine in UL31. Surprisingly, although this UL31 mutation largely restores virus replication, it does not correct the lamina disruption defect, suggesting that, in Vero cells, changes in nuclear shape and gross displacements of lamin A/C may facilitate but are unnecessary for nuclear egress. IMPORTANCE: Herpesvirus nuclear egress is an essential and conserved process that requires close association of the viral capsid with the inner nuclear membrane and budding of the capsid into that membrane. Access to the nuclear membrane and tight curvature of that membrane are thought to require disruption of the nuclear lamina that underlies the inner nuclear membrane, and consistent with this idea, herpesvirus infection induces biochemical and architectural changes at the nuclear membrane. The significance of the nuclear membrane architectural changes is poorly characterized. The results presented here address that deficiency in our understanding and show that a combination of mutations in two of the viral nuclear egress factors results in a failure to accomplish at least two components of lamina disruption while still allowing relatively efficient viral replication, suggesting that changes in nuclear shape and displacement of lamins are not necessary for herpes simplex virus 1 (HSV-1) nuclear egress. PMID- 27654295 TI - HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike. AB - : The trimeric HIV-1 envelope glycoprotein spike (Env) mediates viral entry into cells by using a spring-loaded mechanism that allows for the controlled insertion of the Env fusion peptide into the target membrane, followed by membrane fusion. Env is the focus of vaccine research aimed at inducing protective immunity by antibodies as well as efforts to develop drugs that inhibit the viral entry process. The molecular factors contributing to Env stability and decay need to be understood better in order to optimally design vaccines and therapeutics. We generated viruses with resistance to VIR165, a peptidic inhibitor that binds the fusion peptide of the gp41 subunit and prevents its insertion into the target membrane. Interestingly, a number of escape viruses acquired substitutions in the C1 domain of the gp120 subunit (A60E, E64K, and H66R) that rendered these viruses dependent on the inhibitor. These viruses could infect target cells only when VIR165 was present after CD4 binding. Furthermore, the VIR165-dependent viruses were resistant to soluble CD4-induced Env destabilization and decay. These data suggest that VIR165-dependent Env proteins are kinetically trapped in the unliganded state and require the drug to negotiate CD4-induced conformational changes. These studies provide mechanistic insight into the action of the gp41 fusion peptide and its inhibitors and provide new ways to stabilize Env trimer vaccines. IMPORTANCE: Because of the rapid development of HIV-1 drug resistance, new drug targets need to be explored continuously. The fusion peptide of the envelope glycoprotein can be targeted by anchor inhibitors. Here we describe virus escape from the anchor inhibitor VIR165. Interestingly, some escape viruses became dependent on the inhibitor for cell entry. We show that the identified escape mutations stabilize the ground state of the envelope glycoprotein and should thus be useful in the design of stabilized envelope-based HIV vaccines. PMID- 27654297 TI - Comprehensive Genome Scale Phylogenetic Study Provides New Insights on the Global Expansion of Chikungunya Virus. AB - : Since the India and Indian Ocean outbreaks of 2005 and 2006, the global distribution of chikungunya virus (CHIKV) and the locations of epidemics have dramatically shifted. First, the Indian Ocean lineage (IOL) caused sustained epidemics in India and has radiated to many other countries. Second, the Asian lineage has caused frequent outbreaks in the Pacific islands and in 2013 was introduced into the Caribbean, followed by rapid spread to nearly all of the neotropics. Further, CHIKV epidemics, as well as exported cases, have been reported in central Africa after a long period of perceived silence. To understand these changes and to anticipate the future of the virus, the exact distribution, genetic diversity, transmission routes, and future epidemic potential of CHIKV require further assessment. To do so, we conducted the most comprehensive phylogenetic analysis to date, examined CHIKV evolution and transmission, and explored distinct genetic factors associated with the emergence of the East/Central/South African (ECSA) lineage, the IOL, and the Asian lineage. Our results reveal contrasting evolutionary patterns among the lineages, with growing genetic diversities observed in each, and suggest that CHIKV will continue to be a major public health threat with the potential for further emergence and spread. IMPORTANCE: Chikungunya fever is a reemerging infectious disease that is transmitted by Aedes mosquitoes and causes severe health and economic burdens in affected populations. Since the unprecedented Indian Ocean and Indian subcontinent outbreaks of 2005 and 2006, CHIKV has further expanded its geographic range, including to the Americas in 2013. Its evolution and transmission during and following these epidemics, as well as the recent evolution and spread of other lineages, require optimal assessment. Using newly obtained genome sequences, we provide a comprehensive update of the global distribution of CHIKV genetic diversity and analyze factors associated with recent outbreaks. These results provide a solid foundation for future evolutionary studies of CHIKV that can elucidate emergence mechanisms and also may help to predict future epidemics. PMID- 27654298 TI - The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation. AB - : Virus-like particles (VLPs) are attractive as a vaccine concept. For human respiratory syncytial virus (hRSV), VLP assembly is poorly understood and appears inefficient. Hence, hRSV antigens are often incorporated into foreign VLP systems to generate anti-RSV vaccine candidates. To better understand the assembly, and ultimately to enable efficient production, of authentic hRSV VLPs, we examined the associated requirements and mechanisms. In a previous analysis in HEp-2 cells, the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) were required for formation of filamentous VLPs, which, similar to those of wild-type virus, were associated with the cell surface. Using fluorescence and electron microscopy combined with immunogold labeling, we examined the surfaces of transfected HEp-2 cells and further dissected the process of filamentous VLP formation. Our results show that N is not required. Coexpression of P plus M plus F, but not P plus M, M plus F, or P plus F, induced both viral protein coalescence and formation of filamentous VLPs that resembled wild-type virions. Despite suboptimal coalescence in the absence of P, the M and F proteins, when coexpressed, formed cell surface-associated filaments with abnormal morphology, appearing longer and thinner than wild-type virions. For F, only the carboxy terminus (Fstem) was required, and addition of foreign protein sequences to Fstem allowed incorporation into VLPs. Together, the data show that P, M, and the F carboxy terminus are sufficient for robust viral protein coalescence and filamentous VLP formation and suggest that M-F interaction drives viral filament formation, with P acting as a type of cofactor facilitating the process and exerting control over particle morphology. IMPORTANCE: hRSV is responsible for >100,000 deaths in children worldwide, and a vaccine is not available. Among the potential anti-hRSV approaches are virus-like particle (VLP) vaccines, which, based on resemblance to virus or viral components, can induce protective immunity. For hRSV, few reports are available concerning authentic VLP production or testing, in large part because VLP production is inefficient and the mechanisms underlying particle assembly are poorly understood. Here, we took advantage of the cell-associated nature of RSV particles and used high-resolution microscopy analyses to examine the viral proteins required for formation of wild type-virus-resembling VLPs, the contributions of these proteins to morphology, and the domains involved in incorporation of the antigenically important viral F protein. The results provide new insights that will facilitate future production of hRSV VLPs with defined shapes and compositions and may translate into improved manufacture of live-attenuated hRSV vaccines. PMID- 27654299 TI - Assessment of the PrPc Amino-Terminal Domain in Prion Species Barriers. AB - : Chronic wasting disease (CWD) in cervids and bovine spongiform encephalopathy (BSE) in cattle are prion diseases that are caused by the same protein-misfolding mechanism, but they appear to pose different risks to humans. We are interested in understanding the differences between the species barriers of CWD and BSE. We used real-time, quaking-induced conversion (RT-QuIC) to model the central molecular event in prion disease, the templated misfolding of the normal prion protein, PrPc, to a pathogenic, amyloid isoform, scrapie prion protein, PrPSc We examined the role of the PrPc amino-terminal domain (N-terminal domain [NTD], amino acids [aa] 23 to 90) in cross-species conversion by comparing the conversion efficiency of various prion seeds in either full-length (aa 23 to 231) or truncated (aa 90 to 231) PrPc We demonstrate that the presence of white-tailed deer and bovine NTDs hindered seeded conversion of PrPc, but human and bank vole NTDs did the opposite. Additionally, full-length human and bank vole PrPcs were more likely to be converted to amyloid by CWD prions than were their truncated forms. A chimera with replacement of the human NTD by the bovine NTD resembled human PrPc The requirement for an NTD, but not for the specific human sequence, suggests that the NTD interacts with other regions of the human PrPc to increase promiscuity. These data contribute to the evidence that, in addition to primary sequence, prion species barriers are controlled by interactions of the substrate NTD with the rest of the substrate PrPc molecule. IMPORTANCE: We demonstrate that the amino-terminal domain of the normal prion protein, PrPc, hinders seeded conversion of bovine and white-tailed deer PrPcs to the prion forms, but it facilitates conversion of the human and bank vole PrPcs to the prion forms. Additionally, we demonstrate that the amino-terminal domain of human and bank vole PrPcs requires interaction with the rest of the molecule to facilitate conversion by CWD prions. These data suggest that interactions of the amino terminal domain with the rest of the PrPc molecule play an important role in the susceptibility of humans to CWD prions. PMID- 27654300 TI - PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features. AB - : Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features. IMPORTANCE: The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model. PMID- 27654303 TI - Dimensional Effects of MoS2 Nanoplates Embedded in Carbon Nanofibers for Bifunctional Li and Na Insertion and Conversion Reactions. AB - Controlling structural and morphological features of molybdenum disulfide (MoS2) nanoplates determines anode reaction performance for Li-ion and Na-ion batteries. In this work, we investigate dimensional effects of MoS2 nanoplates randomly embedded in twisted mesoporous carbon nanofibers (MoS2@MCNFs) on Li and Na storage properties. Considering dimensions of the MoS2 nanoplates (e.g., interlayer, lateral distance, and slabs of stacking in number), we controlled thermolysis temperature to synthesize the MoS2 nanoplates with different geometry and optimize them in the hybrid anode for delivering high performance. The MoS2@MCNFs electrode exhibits reversible Li and Na capacities greater than 1000 cycles even at high current density of 1.0 A g-1 (1221.94 mAh g-1 with capacity retention of 95.6% for Li-ion batteries and 447.29 mAh g-1 with capacity retention of 87.11% for Na-ion batteries). We elucidated the insertion, conversion, and interfacial reaction characteristics of the thermosensitive MoS2 nanoplates in the MCNFs, especially associated with a reversible capacity. Our study will hint at rational design of the nanostructured MoS2 electrodes and focus on significance of their dimensional effects on anode performance. PMID- 27654302 TI - Fucoidan Induces ROS-Dependent Apoptosis in 5637 Human Bladder Cancer Cells by Downregulating Telomerase Activity via Inactivation of the PI3K/Akt Signaling Pathway. AB - Preclinical Research Fucoidan, a sulfated polysaccharide, is a compound found in various species of seaweed that has anti-viral, anti-bacterial, anti-oxidant, anti-inflammatory, and immunomodulatory activities; however, the underlying relationship between apoptosis and anti-telomerase activity has not been investigated. Here, we report that fucoidan-induced apoptosis in 5637 human bladder cancer cells was associated with an increase in the Bax/Bcl-2 ratio, the dissipation of the mitochondrial membrane potential (MMP, Deltapsim), and cytosolic release of cytochrome c from the mitochondria. Under the same experimental conditions, fucoidan-treatment decreased hTERT (human telomerase reverse transcriptase) expression and the transcription factors, c-myc and Sp1. This was accompanied by decreased telomerase activity. Fucoidan-treatment also suppressed activation of the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling enhanced fucoidan-induced apoptosis and anti-telomerase activity. Meanwhile, fucoidan treatment increased the generation of intracellular ROS, whereas the over-elimination of ROS by N-acetylcysteine, an anti-oxidant, attenuated fucoidan-induced apoptosis, inhibition of hTERT, c-myc, and Sp1 expression, and reversed fucoidan-induced inactivation of the PI3K/Akt signaling pathway. Collectively, these data indicate that the induction of apoptosis and the inhibition of telomerase activity by fucoidan are mediated via ROS-dependent inactivation of the PI3K/Akt pathway. Drug Dev Res 78 : 37-48, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27654301 TI - A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein. AB - : Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 MUM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. IMPORTANCE: Yellow fever is an acute viral hemorrhagic disease which threatens approximately one billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than seven decades, the low vaccination rate fails to prevent outbreaks in at-risk regions. It has been estimated that up to 1.7 million YFV infections occur in Africa each year, resulting in 29,000 to 60,000 death. Thus far, there is no specific antiviral treatment for yellow fever. To cope with this medical challenge, we identified a benzodiazepine compound that selectively inhibits YFV by targeting the viral NS4B protein. To our knowledge, this is the first report demonstrating in vivo safety and antiviral efficacy of an YFV NS4B inhibitor in an animal model. We have thus reached a critical milestone toward the development of specific antiviral therapeutics for clinical management of yellow fever. PMID- 27654304 TI - Selective Growth of Subnanometer Diameter Single-Walled Carbon Nanotube Arrays in Hydrogen-Free CVD. AB - Small diameter single-walled carbon nanotube (SWNT) arrays with larger bandgap are more desirable as near-infrared optical absorbers for the fabrication of high performance photovoltaic and photodetector devices. We report herein a rational approach to selective growth of well-aligned subnanometer diameter (~84% between 0.75 and 0.95 nm) SWNT arrays with a density of 0.3-0.5 tubes/MUm on quartz surfaces using solid Mo2C catalysts for short-time growth by low carbon feeding in hydrogen-free CVD. These subnanometer diameter SWNTs have a narrow chirality distribution (the ratio of (8,4), (8,5) and (7,6) is higher than 73%). During nanotube growth, only small size Mo nanoparticles are carbonized into stable Mo2C for catalyzing the growth of SWNTs through low carbon feeding rate over short time in the hydrogen-free environment, whereas larger catalysts are inactive due to underfeeding. Meanwhile, solid Mo2C catalysts are effective in reducing the chirality distributions of the as-grown SWNTs. Additionally, combining an annealing process after loading catalyst on the sapphire substrates, the average density is increased to ~15 tubes/MUm while maintaining small diameter and narrow chirality distribution. Our results offer more choices for structurally controlled growth of aligned-SWNTs, with potential applications in nanoelectronics. PMID- 27654306 TI - Opinion of Spanish Consumers on Hydrosustainable Pistachios. AB - Fruits and vegetables cultivated under controlled deficit irrigation (CDI) are called hydrosustainable (hydroSOS) products and have its own personality and are environmentally-friendly. Focus groups helped in classifying key farming, sensory, and health concepts associated with CDI-grown pistachios. Besides, focus groups also helped in stating that a logo was needed for these special foods, and that a hydroSOS index is also essential to certify that the products have been controlled by a control board. Conjoint analysis was used to check which attributes could be helpful in promoting CDI-grown pistachios among Spanish consumers in a 1st step toward the European Union (EU) market. It was clearly proved that the main silo of properties driving the attention of Spanish consumers was that related to health. The most important attributes for pistachios were "product of Spain," "rich in antioxidant," and "crunchy"; this finding was clearly related to the popularity of regional foods, the preoccupation of European consumers for their health, and the joy related to the crunchiness of toasted nuts, respectively. The use of these 3 concepts, together with the use of the hydroSOS logo, will be essential to promote hydroSOS pistachios among Spanish and EU consumers. Finally, it is important to highlight that in general Spanish consumers were willing to pay an extra amount of 1.0 euros per kg of hydroSOS pistachios. These earnings will be essential to convince Spanish farmers to implement CDI strategies and have a sustainable and environmental-friendly use of the irrigation water. PMID- 27654307 TI - Application of texture analysis based on apparent diffusion coefficient maps in discriminating different stages of rectal cancer. AB - PURPOSE: To explore the potential of texture analysis based on apparent diffusion coefficient (ADC) maps, as a predictor of local invasion depth (stage pT1-2 versus pT3-4) and nodal status (pN0 versus pN1-2) of rectal cancer. MATERIALS AND METHODS: Sixty-eight patients with rectal cancer underwent preoperative magnetic resonance (MR) imaging including diffusion weighted imaging (DWI) at a 3.0 Tesla system. Routine ADC variables (ADCmean , ADCmin , ADCmax ), histogram features (skewness, kurtosis) and gray level co-occurrence matrix features (entropy, contrast, correlation) were compared between pT1-2 and pT3-4 stages, between pN0 and pN1-2 stages. RESULTS: Skewness, entropy, and contrast were significantly lower in patients with pT1-2 as compared to those with pT3-4 tumors (0.166 versus 0.476, P = 0.015; 3.212 versus 3.441 P = 0.004; 10.773 versus 13.596, P = 0.017). Furthermore, skewness and entropy were identified as independent predictors for extramural invasion of tumors (stage pT3-4). Significant differences were observed between pN0 and pN1-2 tumors with respect to ADCmean (1.152 versus 1.044, P = 0.029), ADCmax (1.692 versus 1.460, P = 0.006) and entropy (3.299 versus 3.486, P = 0.015). ADCmax. and entropy were independent predictors of positive nodal status. CONCLUSION: Texture analysis on ADC maps could provide valuable information in identifying locally advanced rectal cancer. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1798-1808. PMID- 27654305 TI - Antioxidant Response of Chronic Wounds to Hyperbaric Oxygen Therapy. AB - We analyzed the effects of the clinical hyperbaric oxygen therapy (HBOT) on the plasma antioxidant response and levels of endothelin-1, Interleukine-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic wounds (20.2+/ 10.0 months without healing). They received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20 before and 2 hours after the HBOT. An additional blood sample was collected 1 month after wound recovery. Serum creatine kinase activity decreased progressively in accordance with the wound healing. Plasma catalase activity significantly increased after the first and fifth sessions of HBOT. Plasma myeloperoxidase activity reported significantly lower values after sessions. Plasma VEGF and IL-6 increased after sessions. Endothelin-1 levels were progressively decreasing during the HBOT, being significant at the session 20. Plasma malondialdehyde concentration was significantly reduced at the last session. Both creatine kinase activity and malondialdehyde levels were maintained lower 1 month after wound recovery respect to initial values. In conclusion, HBOT enhanced the plasma antioxidant defenses and may contribute to activate the healing resolution, angiogenesis and vascular tone regulation by increasing the VEGF and IL-6 release and the endothelin-1 decrease, which may be significant factors in stimulating wound healing. PMID- 27654308 TI - Polyphosphoesters: New Trends in Synthesis and Drug Delivery Applications. AB - Polymers with repeating phosphoester linkages in the backbone are biodegradable materials that emerge as a promising class of novel biomaterials, especially in the field of drug delivery systems. In contrast to aliphatic polyesters, the pentavalency of the phosphorus atom offers a large diversity of structures and as a consequence a wide range of properties for these materials. In this paper, it is focused on the synthesis of well-defined polyphosphoesters (PPEs) by organocatalyzed ring-opening polymerization, improving the functionalities by combination with click reactions, degradation of functional PPEs and their cytotoxicity, and inputs for applications in drug delivery. PMID- 27654309 TI - Lemont B. Kier: Art, Science and Green Cheese. PMID- 27654311 TI - Reverse Takotsubo syndrome in a patient with diagnosed multiple sclerosis. PMID- 27654310 TI - Perioperative complications of conduit urinary diversion with concomitant cystectomy for benign indications: A population-based analysis. AB - AIMS: Beyond single-institution case series, limited data are available to describe risks of performing a concurrent cystectomy at the time of urinary diversion for benign end-stage lower urinary tract dysfunction. Using a population-representative sample, this study aimed to analyze factors associated with perioperative complications in patients undergoing urinary diversion with or without cystectomy. METHODS: A representative sample of patients undergoing urinary diversion for benign indications was identified from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1998 to 2011. Perioperative complications of urinary diversion with and without concomitant cystectomy were identified and coded using the International Classification of Diseases, version 9. Multivariate logistic regression models identified hospital and patient-level characteristics associated with complications of concomitant cystectomy with urinary diversion. RESULTS: There were 15,717 records for urinary diversion identified, of which 31.8% demonstrated perioperative complications: urinary diversion with concurrent cystectomy (35.0%) and urinary diversion without concomitant cystectomy (30.6%). Comparing the two groups, a concomitant cystectomy at the time of urinary diversion was significantly associated with a complication (OR = 1.23, 95%CI: 1.03-1.48). Comorbid conditions of obesity, pulmonary circulation disease, drug abuse, weight loss, and electrolyte disorders were positively associated with a complication, while private insurance and southern geographic region were negatively associated. CONCLUSIONS: A concomitant cystectomy with urinary diversion for refractory lower urinary tract dysfunction elevates risk in this population-representative sample, particularly in those with certain comorbid conditions. This analysis provides critical information for preoperative patient counseling. PMID- 27654312 TI - Cardiac contractility modulation: a new treatment option for chronic heart failure in Poland. PMID- 27654313 TI - "Grafting" of Coordination Complex Modified Polyoxometalate on Ethylenediamine Planted Polyvinylidene Fluoride: Superhydrophilic Composite Membrane for Oxytetracycline Treatment. AB - Under the guide of chemical bonding, a composite membrane had been fabricated successfully through grafting of a coordination complex modified polyoxometalate to an ethylenediamine planted polyvinylidene fluoride. Compared with neat polyvinylidene fluoride membrane, the oxytetracycline adsorption capacity of the polyoxometalate grafted composite membrane has been improved to a great extent. In addition, this polyoxometalate grafted composite membrane also exhibits excellent hydrophilicity, which leads to a clear enhancement in its antifouling properties. Besides oxytetracycline, its performances in the removal of other tetracycline-type antibiotics, such as tetracycline and doxycycline, also looks outstanding. Furthermore, after successive adsorption and desorption experiments, the pollutant removal activity and antifouling property of this composite membrane are well retained, which suggests it is stable for removing tetracycline type antibiotics in waste water treatment processes. PMID- 27654314 TI - Hydrogen peroxide is a central determinant of oral polymicrobial synergy. PMID- 27654316 TI - The Cost-Effectiveness of Integrating HIV Counseling and Testing into Primary Health Care in the Ukraine. AB - We estimate the number of HIV cases diagnosed, costs, and cost per HIV case detected associated with integrating HIV counseling and testing (HCT) into primary health care facilities in Ukraine. The study uses a difference-in difference design with four districts implementing the intervention compared to 20 districts where HCT were offered only at specialized HIV clinics. There was a 2.01 (95 % CI: 1.12-3.61) times increase in the number of HIV cases detected per capita in intervention districts compared to other districts. The incremental cost of the intervention was $21,017 and the incremental cost per HIV case detected was $369. The average cost per HIV case detected before the intervention was $558. Engaging primary health care facilities to provide HCT is likely desirable from an efficiency point-of-view. However, the affordability of the intervention needs to be assessed because expansion will require additional investment. PMID- 27654317 TI - Integrated Photoelectrochemical Solar Energy Conversion and Organic Redox Flow Battery Devices. AB - Building on regenerative photoelectrochemical solar cells and emerging electrochemical redox flow batteries (RFBs), more efficient, scalable, compact, and cost-effective hybrid energy conversion and storage devices could be realized. An integrated photoelectrochemical solar energy conversion and electrochemical storage device is developed by integrating regenerative silicon solar cells and 9,10-anthraquinone-2,7-disulfonic acid (AQDS)/1,2-benzoquinone 3,5-disulfonic acid (BQDS) RFBs. The device can be directly charged by solar light without external bias, and discharged like normal RFBs with an energy storage density of 1.15 Wh L-1 and a solar-to-output electricity efficiency (SOEE) of 1.7 % over many cycles. The concept exploits a previously undeveloped design connecting two major energy technologies and promises a general approach for storing solar energy electrochemically with high theoretical storage capacity and efficiency. PMID- 27654315 TI - Optimal echo time for functional MRI of the infant brain identified in response to noxious stimulation. AB - PURPOSE: Blood oxygen level dependent (BOLD) brain activity, measured using functional MRI (fMRI), is dependent on the echo time (TE) and the reversible spin spin relaxation time constant ( T2*) that describes the decay of transverse magnetization. Use of the optimal TE during fMRI experiments allows maximal sensitivity to BOLD to be achieved. Reports that T2* values are longer in infants (due to higher water concentrations and lower lipid content) have led to the use of longer TEs during infant fMRI experiments; however, the optimal TE has not been established. METHODS: In this study, acute experimental mildly noxious stimuli were applied to the heel in 12 term infants (mean gestational age = 40 weeks, mean postnatal age = 3 days); and the percentage change in BOLD activity was calculated across a range of TEs, from 30 to 70 ms, at 3 Tesla. In addition, T2* maps of the whole brain were collected in seven infants. RESULTS: The maximal change in BOLD occurred at a TE of 52 ms, and the average T2* across the whole brain was 99 ms. CONCLUSION: A TE of approximately 50 ms is recommended for use in 3T fMRI investigations in term infants. Magn Reson Med 78:625-631, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID- 27654318 TI - Patterns of preference and practice: bridging actors in wildfire response networks in the American Northwest. AB - The roles of bridging actors in emergency response networks can be important to disaster response outcomes. This paper is based on an evaluation of wildfire preparedness and response networks in 21 large-scale wildfire events in the wildland-urban interface near national forests in the American Northwest. The study investigated how key individuals in responder networks anticipated seeking out specific people in perceived bridging roles prior to the occurrence of wildfires, and then captured who in fact assumed these roles during actual large scale events. It examines two plausible, but contradictory, bodies of theory similarity and dissimilarity-that suggest who people might seek out as bridgers and who they would really go to during a disaster. Roughly one-half of all pre fire nominations were consistent with similarity. Yet, while similarity is a reliable indicator of how people expect to organise, it does not hold up for how they organise during the real incident. PMID- 27654319 TI - A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney. AB - Normothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ. Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters. The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid-base environment in this small series. In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid-base environment. PMID- 27654321 TI - Minimum Variance Approaches to Ultrasound Pixel-Based Beamforming. AB - We analyze the principles underlying minimum variance distortionless response (MVDR) beamforming in order to integrate it into a pixel-based algorithm. There is a challenge posed by the low echo signal-to-noise ratio (eSNR) when calculating beamformer contributions at pixels far away from the beam centreline. Together with the well-known scarcity of samples for covariance matrix estimation, this reduces the beamformer performance and degrades the image quality. To address this challenge, we implement the MVDR algorithm in two different ways. First, we develop the conventional minimum variance pixel-based (MVPB) beamformer that performs the MVDR after the pixel-based superposition step. This involves a combination of methods in the literature, extended over multiple transmits to increase the eSNR. Then we propose the coherent MVPB beamformer, where the MVDR is applied to data within individual transmits. Based on pressure field analysis, we develop new algorithms to improve the data alignment and matrix estimation, and hence overcome the low-eSNR issue. The methods are demonstrated on data acquired with an ultrasound open platform. The results show the coherent MVPB beamformer substantially outperforms the conventional MVPB in a series of experiments, including phantom and in vivo studies. Compared to the unified pixel-based beamformer, the newest delay-and-sum algorithm in [1], the coherent MVPB performs well on regions that conform to the diffuse scattering assumptions on which the minimum variance principles are based. It produces less good results for parts of the image that are dominated by specular reflections. PMID- 27654320 TI - Unsupervised Learning for Robust Respiratory Signal Estimation From X-Ray Fluoroscopy. AB - Respiratory signals are required for image gating and motion compensation in minimally invasive interventions. In X-ray fluoroscopy, extraction of a respiratory signal can be challenging due to characteristics of interventional imaging, in particular injection of contrast agent and automatic exposure control. We present a novel method for respiratory signal extraction based on dimensionality reduction that can tolerate these events. Images are divided into patches of multiple sizes. Low-dimensional embeddings are generated for each patch using illumination-invariant kernel PCA. Patches with respiratory information are selected automatically by agglomerative clustering. The signals from this respiratory cluster are combined robustly to a single respiratory signal. In the experiments, we evaluate our method on a variety of scenarios. If the diaphragm is visible, we track its superior-inferior motion as ground truth. Our method has a correlation coefficient of more than 91% with the ground truth irrespective of whether or not contrast agent injection or automatic exposure control occur. Additionally, we show that very similar signals are estimated from biplane sequences and from sequences without visible diaphragm. Since all these cases are handled automatically, the method is robust enough to be considered for use in a clinical setting. PMID- 27654323 TI - Spatial Prediction Filtering of Acoustic Clutter and Random Noise in Medical Ultrasound Imaging. AB - One of the major challenges in array-based medical ultrasound imaging is the image quality degradation caused by sidelobes and off-axis clutter, which is an inherent limitation of the conventional delay-and-sum (DAS) beamforming operating on a finite aperture. Ultrasound image quality is further degraded in imaging applications involving strong tissue attenuation and/or low transmit power. In order to effectively suppress acoustic clutter from off-axis targets and random noise in a robust manner, we introduce in this paper a new adaptive filtering technique called frequency-space (F-X) prediction filtering or FXPF, which was first developed in seismic imaging for random noise attenuation. Seismologists developed FXPF based on the fact that linear and quasilinear events or wavefronts in the time-space (T-X) domain are manifested as a superposition of harmonics in the frequency-space (F-X) domain, which can be predicted using an auto-regressive (AR) model. We describe the FXPF technique as a spectral estimation or a direction-of-arrival problem, and explain why adaptation of this technique into medical ultrasound imaging is beneficial. We apply our new technique to simulated and tissue-mimicking phantom data. Our results demonstrate that FXPF achieves CNR improvements of 26% in simulated noise-free anechoic cyst, 109% in simulated anechoic cyst contaminated with random noise of 15 dB SNR, and 93% for experimental anechoic cyst from a custom-made tissue-mimicking phantom. Our findings suggest that FXPF is an effective technique to enhance ultrasound image contrast and has potential to improve the visualization of clinically important anatomical structures and diagnosis of diseased conditions. PMID- 27654322 TI - Isotropic Total Variation Regularization of Displacements in Parametric Image Registration. AB - Spatial regularization is essential in image registration, which is an ill-posed problem. Regularization can help to avoid both physically implausible displacement fields and local minima during optimization. Tikhonov regularization (squared l2 -norm) is unable to correctly represent non-smooth displacement fields, that can, for example, occur at sliding interfaces in the thorax and abdomen in image time-series during respiration. In this paper, isotropic Total Variation (TV) regularization is used to enable accurate registration near such interfaces. We further develop the TV-regularization for parametric displacement fields and provide an efficient numerical solution scheme using the Alternating Directions Method of Multipliers (ADMM). The proposed method was successfully applied to four clinical databases which capture breathing motion, including CT lung and MR liver images. It provided accurate registration results for the whole volume. A key strength of our proposed method is that it does not depend on organ masks that are conventionally required by many algorithms to avoid errors at sliding interfaces. Furthermore, our method is robust to parameter selection, allowing the use of the same parameters for all tested databases. The average target registration error (TRE) of our method is superior (10% to 40%) to other techniques in the literature. It provides precise motion quantification and sliding detection with sub-pixel accuracy on the publicly available breathing motion databases (mean TREs of 0.95 mm for DIR 4D CT, 0.96 mm for DIR COPDgene, 0.91 mm for POPI databases). PMID- 27654324 TI - Outcomes of children with rhabdomyosarcoma treated with intensive chemotherapy, surgery, and radiotherapy through a period of protocol revision at a South African center, 1990-2010. AB - A total of 75 children with biopsy-proven rhabdomyosarcoma were treated at our institution between 1990 and 2010. Five-year overall survival (OS) for the entire cohort was 58.7%. OS by stage was as follows: Stage 1 (80%), Stage 2 (80%), Stage 3 (54.1%), and Stage 4 (38.5%). There was a trend to suggest that revision of treatment approaches improved crude survival over time: pre-2003 (OS 42.1%); 2003 2005 (OS 50.0%); 2005-2010 (OS 60.8%). PMID- 27654325 TI - Evolution of dark colour in toucans (Ramphastidae): a case of molecular adaptation? AB - In the last decades, researchers have been able to determine the molecular basis of some phenotypes, to test for evidence of natural selection upon them, and to demonstrate that the same genes or genetic pathways can be associated with convergent traits. Colour traits are often subject to natural selection because even small changes in these traits can have a large effect on fitness via camouflage, sexual selection or other mechanisms. The melanocortin-1 receptor locus (MC1R) is frequently associated with intraspecific coat colour variation in vertebrates, but it has been far harder to demonstrate that this locus is involved in adaptive interspecific colour differences. Here, we investigate the contribution of the MC1R gene to the colour diversity found in toucans (Ramphastidae). We found divergent selection on MC1R in the clade represented by the genus Ramphastos and that this coincided with the evolution of darker plumage in members of this genus. Using phylogenetically corrected correlations, we show significant and specific relationships between the rate of nonsynonymous change in MC1R (dN) and plumage darkness across Ramphastidae, and also between the rate of functionally significant amino acid changes in MC1R and plumage darkness. Furthermore, three of the seven amino acid changes in MC1R that occurred in the ancestral Ramphastos branch are associated with melanism in other birds. Taken together, our results suggest that the dark colour of Ramphastos toucans was related to nonsynonymous substitutions in MC1R that may have been subject to positive selection or to a relaxation of selective pressure. These results also demonstrate a quantitative relationship between gene and phenotype evolution, representing an example of how MC1R molecular evolution may affect macroevolution of plumage phenotypes. PMID- 27654326 TI - Moderate to vigorous physical activity, not sedentary time, is associated with total and regional adiposity in a sample of UK adults at risk of type 2 diabetes. AB - How sedentary time (ST) relates to total and regional adiposity and whether these associations are independent of moderate- to vigorous-intensity physical activity (MVPA) are of clinical and public health interest. We assessed the relationship between objectively measured MVPA, ST and ST breaks in adults at risk of type 2 diabetes. The sample consisted of 163 adults (37-75 years) recruited from primary care. Dual energy x-ray absorptiometry (iDXA, GE Corp) was used to estimate total and regional (appendages and trunk) fat mass as well as fat mass in the abdominal (android) and hip/thigh (gynoid) regions. The Actigraph GT3X was worn for 7 days (participants with ?4 valid days included herein) and published cut-points were applied to 15 s epoch data to estimate mean MVPA, ST and breaks in ST. Multiple regression investigated associations between both ST and MVPA with total and regional adiposity without and with adjustment for known and potential confounders (including total lean mass) and for each other. MVPA was negatively and significantly associated with total (b = -62; p = 0.002), and regional (p < 0.05) adiposity before and after adjusting for confounders including ST. Although ST was positively and significantly associated with total (b = 46.4; p = 0.002) and regional adiposity (all p ? 0.007), these relationships disappeared after adjustment for MVPA (p > 0.05). Sedentary breaks were not significantly related to adiposity before or after adjustment. An age-by-MVPA interaction for total, android, gynoid and trunk fat revealed that MVPA did not remain significant when controlling for ST and other covariates in the adults over 65 years old. In this sample of adults at risk of type 2 diabetes, MVPA, and not ST, was associated with total and regional adiposity after adjustment for each other. However, in older adults at risk of T2D weight related benefits may be gained from reducing daily ST and increasing MVPA. PMID- 27654327 TI - Impact of telephone nursing education program for equity in healthcare. AB - BACKGROUND: The Swedish Healthcare Act prescribes that healthcare should be provided according to needs and with respect for each person's human dignity. The goal is equity in health for the whole population. In spite of this, studies have revealed that Swedish healthcare is not always provided equally. This has also been observed in telephone nursing. Therefore, the aim of the present study was to investigate if and how an educational intervention can improve awareness of equity in healthcare among telephone nurses. METHODS: The study had a quasi experimental design, with one intervention group and one control group. A base line measurement was performed before an educational intervention and a follow-up measurement was made afterwards in both groups, using a study specific questionnaire in which fictive persons of different age, gender and ethnicity were assessed concerning, e.g., power over one's own life, quality of life and experience of discrimination. The educational intervention consisted of a web based lecture, literature and a seminar, covering aspects of inequality in healthcare related to gender, age and ethnicity, and gender and intersectionality theories as explaining models for these conditions. RESULTS: The results showed few significant differences before and after the intervention in the intervention group. Also in the control group few significant differences were found in the second measurement, although no intervention was performed in that group. The reason might be that the instrument used was not sensitive enough to pick up an expected raised awareness of equity in healthcare, or that solely the act of filling out the questionnaire can create a sort of intervention effect. Fictive persons born in Sweden and of young age were assessed to have a higher Good life index than the fictive persons born outside Europe and of higher age in all assessments. CONCLUSION: The results are an imperative that equity in healthcare still needs to be educated and discussed in different healthcare settings. The intervention and questionnaire were designed to fit telephone nurses, but could easily be adjusted to suit other professional groups, who need to increase their awareness of equity in healthcare. PMID- 27654328 TI - Pre- and undiagnosed-hypertension in urban Chinese adults: a population-based cross-sectional study. AB - Hypertension is common in adults and often undiagnosed, and the prevalence of pre and undiagnosed-hypertension remains unclear. We aimed to investigate the prevalence of pre- and undiagnosed-hypertension and their correlates among urban Chinese adults. A total of 7435 participants aged 20-79 were included in this study. Data on demographics, lifestyle and medical history were collected through a structured interview. Pre- and undiagnosed-hypertension was defined as systolic blood pressure/ diastolic blood pressure (SBP/DBP) of 120-139/80-89 mm Hg and SBP?140 mm Hg and/or DBP?90 mm Hg, respectively, in participants without a history of hypertension and use of antihypertensive medication. Prevalence rates were calculated and standardized using local age- and gender-specific census data. Data were analysed using multinomial logistic regression with adjustment for potential confounders. Of all the participants, 2726 (36.7%) were diagnosed with pre-hypertension and 919 (12.3%) with undiagnosed-hypertension. Undiagnosed hypertension accounted for 37.3% of all participants with hypertension. The prevalence of pre-hypertension gradually decreased with age, while undiagnosed hypertension increased, although presenting different changing patterns among men and women. In a fully adjusted multinomial logistic regression, age, male sex, low socio-economic status (SES), abdominal obesity, alcohol drinking, physical inactivity and type 2 diabetes mellitus (T2DM) were significantly associated with increased odds of pre- and undiagnosed-hypertension. In conclusions, the prevalence of pre- and undiagnosed-hypertension was ~50% among urban Chinese adults. Abdominal obesity, low SES, alcohol drinking, physical inactivity and T2DM may be indicators for pre- and undiagnosed-hypertension. PMID- 27654329 TI - Effects of blueberry supplementation on blood pressure: a systematic review and meta-analysis of randomized clinical trials. AB - Blueberries belong to the genus Vaccinium of the family Ericaceae. A series of epidemiological studies have demonstrated that blueberry polyphenols, particularly blueberry anthocyanins provide significant beneficial effects for humans. However, the findings of clinical studies have been equivocal. Therefore, we sought to assess the potential anti-hypertensive effects of blueberry supplementation through a meta-analysis of available randomized controlled trials (RCTs). A comprehensive literature search of PubMed, The Cochrane Library, AMED (Allied and Complementary Medicine Database), Embase, Web of Science, Wanfang Database, and China National Knowledge Infrastructure were performed to identify potential studies published before June 2015. The standardized mean difference and 95% confidence interval (CI) were used as summary statistics. Net changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) between the blueberry and placebo groups were calculated by subtracting the values at the end of follow-up from those at baseline. Meta-regression was used to identify potential moderators of effect size. Six RCT studies with 204 participants were included in our meta-analysis. There was no significant effect of blueberry supplementation on changes in blood pressure (BP) relative to baseline, and there was a mean difference of -0.28 (95% CI: -1.11 to 0.56, I2=87%) and -0.5 (95% CI: 1.24 to 0.24, I2=84%) mmHg for SBP and DBP, respectively. In summary, the results from this meta-analysis do not favor any clinical efficacy of blueberry supplementation in improving BP. Further well-designed larger RCTs are required to verify the association between blueberry supplementation and BP. PMID- 27654330 TI - Eye-Gaze Analysis of Facial Emotion Recognition and Expression in Adolescents with ASD. AB - Impaired emotion recognition and expression in individuals with autism spectrum disorder (ASD) may contribute to observed social impairment. The aim of this study was to examine the role of visual attention directed toward nonsocial aspects of a scene as a possible mechanism underlying recognition and expressive ability deficiency in ASD. One recognition and two expression tasks were administered. Recognition was assessed in force-choice paradigm, and expression was assessed during scripted and free-choice response (in response to emotional stimuli) tasks in youth with ASD (n = 20) and an age-matched sample of typically developing youth (n = 20). During stimulus presentation prior to response in each task, participants' eye gaze was tracked. Youth with ASD were less accurate at identifying disgust and sadness in the recognition task. They fixated less to the eye region of stimuli showing surprise. A group difference was found during the free-choice response task, such that those with ASD expressed emotion less clearly but not during the scripted task. Results suggest altered eye gaze to the mouth region but not the eye region as a candidate mechanism for decreased ability to recognize or express emotion. Findings inform our understanding of the association between social attention and emotion recognition and expression deficits. PMID- 27654332 TI - Antibiotics: where to throw the spanner in the ribosomal machinery? AB - The sheer molecular scale of the ribosome is intimidating to the traditional drug designer. By analyzing the ribosome as a series of 12 key target sites, this review seeks to make the ribosome ligand design process more manageable. Analysis of recently evaluated ribosomal structures, particularly those with bound antibiotics, indicates where the ligand target sites are located. This review employs current research data to map antibiotic binding across the ribosome. A number of neighboring ligand-binding sites are often contiguous and can be combined. Ligands that bind in close proximity can be combined into hybrid structures. The different ways antibiotics disrupt ribosomal function are also discussed. Antibiotics tend to inhibit conformational changes that are essential to the ribosomal mechanism. PMID- 27654333 TI - Stabilization of Paclitaxel-Conjugated Micelles by Cross-Linking with Cystamine Compromises the Antitumor Effects against Two- and Three-Dimensional Tumor Cellular Models. AB - Paclitaxel (PTX)-conjugated micelles provide a promising tool for the treatment of prostate cancer. Core cross-linking by incorporating a disulfide bridge is a useful approach to improving the in vivo stability of polymeric micelles. This paper aims to investigate the effects of different degrees of cross-linking on the antitumor efficacy of micelles formed by poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer. Both two-dimensional (2D) and three-dimensional (3D) in vitro prostate tumor cell models were used to evaluate the un-cross-linked and cross-linked micelles. The cytotoxicity decreased with an increase in the degree of cross-linking upon being tested with 2D cultured cells, and all micelles remained less cytotoxic than free PTX. In the 3D prostate MCTS model, however, there was no statistical difference between the performance of un-cross-linked micelles and free PTX, while increasing cross-linking densities led to significantly relevant decreases in the antitumor efficacy of micelles. These results are contradictory to our previous research using an irreversible cross-linker (1,8-diaminooctane) to stabilize POEGMEA-b-PCEA-PTX conjugate micelles where it was shown that cross-linking accelerates and improves the effects of the micelles when compared to those of un cross-linked micelles. Further studies that aim to investigate the underlying mechanisms of disulfide bonds when micelles are internalized into cells are desired. PMID- 27654331 TI - The application of transcriptomic data in the authentication of beef derived from contrasting production systems. AB - BACKGROUND: Differences between cattle production systems can influence the nutritional and sensory characteristics of beef, in particular its fatty acid (FA) composition. As beef products derived from pasture-based systems can demand a higher premium from consumers, there is a need to understand the biological characteristics of pasture produced meat and subsequently to develop methods of authentication for these products. Here, we describe an approach to authentication that focuses on differences in the transcriptomic profile of muscle from animals finished in different systems of production of practical relevance to the Irish beef industry. The objectives of this study were to identify a panel of differentially expressed (DE) genes/networks in the muscle of cattle raised outdoors on pasture compared to animals raised indoors on a concentrate based diet and to subsequently identify an optimum panel which can classify the meat based on a production system. RESULTS: A comparison of the muscle transcriptome of outdoor/pasture-fed and Indoor/concentrate-fed cattle resulted in the identification of 26 DE genes. Functional analysis of these genes identified two significant networks (1: Energy Production, Lipid Metabolism, Small Molecule Biochemistry; and 2: Lipid Metabolism, Molecular Transport, Small Molecule Biochemistry), both of which are involved in FA metabolism. The expression of selected up-regulated genes in the outdoor/pasture-fed animals correlated positively with the total n-3 FA content of the muscle. The pathway and network analysis of the DE genes indicate that peroxisome proliferator activated receptor (PPAR) and FYN/AMPK could be implicit in the regulation of these alterations to the lipid profile. In terms of authentication, the expression profile of three DE genes (ALAD, EIF4EBP1 and NPNT) could almost completely separate the samples based on production system (95 % authentication for animals on pasture-based and 100 % for animals on concentrate- based diet) in this context. CONCLUSIONS: The majority of DE genes between muscle of the outdoor/pasture-fed and concentrate-fed cattle were related to lipid metabolism and in particular beta-oxidation. In this experiment the combined expression profiles of ALAD, EIF4EBP1 and NPNT were optimal in classifying the muscle transcriptome based on production system. Given the overall lack of comparable studies and variable concordance with those that do exist, the use of transcriptomic data in authenticating production systems requires more exploration across a range of contexts and breeds. PMID- 27654335 TI - Assessment of Microbiological Diagnosis of Active Pulmonary Tuberculosis: Culture on Liquid Medium with or without Solid Medium. PMID- 27654334 TI - Clinical Utility of On-Demand Multiplex Respiratory Pathogen Testing among Adult Outpatients. AB - Multiplex tests for respiratory tract infections include up to 20 targets for common pathogens, predominantly viruses. A specific therapeutic intervention is available for individuals testing positive for influenza viruses (oseltamivir), and it is potentially beneficial to identify non-influenza viruses to avoid unnecessary antibiotic use. We evaluated antimicrobial prescriptions following respiratory pathogen testing among outpatients at a large Veterans Administration (VA) medical center. Results of the FilmArray respiratory panel (BioFire, Salt Lake City, UT) from 15 December 2014 to 15 April 2015 were evaluated among 408 outpatients, and patient medical records were reviewed. Differences in antibiotic and oseltamivir prescription rates were analyzed. Among 408 patients tested in outpatient centers (emergency departments, urgent care clinics, and outpatient clinics), 295 (72.3%) were managed as outpatients. Among these 295 outpatients, 105 (35.6%) tested positive for influenza virus, 109 (36.9%) tested positive for a non-influenza virus pathogen, and 81 (27.5%) had no respiratory pathogen detected. Rates of oseltamivir and antibiotic prescriptions were significantly different among the three test groups (chi-squared values of 167.6 [P < 0.0001] and 10.48 [P = 0.005], respectively), but there was no significant difference in antibiotic prescription rates between the non-influenza virus pathogen group and those who tested negative (chi-square value, 0; P = 1.0). Among adult outpatients, testing positive for influenza virus was associated with receiving fewer antibiotic prescriptions, but no such effect was seen for those who tested positive for a non-influenza virus. These data suggest that testing for influenza viruses alone may be sufficient and more cost-effective than multiplex pathogen testing for outpatients. PMID- 27654336 TI - Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory. AB - Melioidosis is a potentially fatal infection caused by the bacterium Burkholderia pseudomallei Clinical diagnosis of melioidosis can be challenging since there is no pathognomonic clinical syndrome, and the organism is often misidentified by methods used routinely in clinical laboratories. Although the disease is more prevalent in Thailand and northern Australia, sporadic cases may be encountered in areas where it is not endemic, including the United States. Since the organism is considered a tier 1 select agent according to the Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service, clinical laboratories must be proficient at rapidly recognizing isolates suspicious for B. pseudomallei, be able to safely perform necessary rule-out tests, and to refer suspect isolates to Laboratory Response Network reference laboratories. In this minireview, we report a case of melioidosis encountered at our institution and discuss the laboratory challenges encountered when dealing with clinical isolates suspicious for B. pseudomallei or clinical specimens from suspected melioidosis cases. PMID- 27654337 TI - A Multilaboratory, Multicountry Study To Determine Bedaquiline MIC Quality Control Ranges for Phenotypic Drug Susceptibility Testing. AB - The aim of this study was to establish standardized drug susceptibility testing (DST) methodologies and reference MIC quality control (QC) ranges for bedaquiline, a diarylquinoline antimycobacterial, used in the treatment of adults with multidrug-resistant tuberculosis. Two tier-2 QC reproducibility studies of bedaquiline DST were conducted in eight laboratories using Clinical Laboratory and Standards Institute (CLSI) guidelines. Agar dilution and broth microdilution methods were evaluated. Mycobacterium tuberculosis H37Rv was used as the QC reference strain. Bedaquiline MIC frequency, mode, and geometric mean were calculated. When resulting data occurred outside predefined CLSI criteria, the entire laboratory data set was excluded. For the agar dilution MIC, a 4-dilution QC range (0.015 to 0.12 MUg/ml) centered around the geometric mean included 95.8% (7H10 agar dilution; 204/213 observations with one data set excluded) or 95.9% (7H11 agar dilution; 232/242) of bedaquiline MICs. For the 7H9 broth microdilution MIC, a 3-dilution QC range (0.015 to 0.06 MUg/ml) centered around the mode included 98.1% (207/211, with one data set excluded) of bedaquiline MICs. Microbiological equivalence was demonstrated for bedaquiline MICs determined using 7H10 agar and 7H11 agar but not for bedaquiline MICs determined using 7H9 broth and 7H10 agar or 7H9 broth and 7H11 agar. Bedaquiline DST methodologies and MIC QC ranges against the H37Rv M. tuberculosis reference strain have been established: 0.015 to 0.12 MUg/ml for the 7H10 and 7H11 agar dilution MICs and 0.015 to 0.06 MUg/ml for the 7H9 broth microdilution MIC. These methodologies and QC ranges will be submitted to CLSI and EUCAST to inform future research and provide guidance for routine clinical bedaquiline DST in laboratories worldwide. PMID- 27654338 TI - A Multilaboratory, Multicountry Study To Determine MIC Quality Control Ranges for Phenotypic Drug Susceptibility Testing of Selected First-Line Antituberculosis Drugs, Second-Line Injectables, Fluoroquinolones, Clofazimine, and Linezolid. AB - Our objective was to establish reference MIC quality control (QC) ranges for drug susceptibility testing of antimycobacterials, including first-line agents, second line injectables, fluoroquinolones, and World Health Organization category 5 drugs for multidrug-resistant tuberculosis using a 7H9 broth microdilution MIC method. A tier-2 reproducibility study was conducted in eight participating laboratories using Clinical Laboratory and Standards Institute (CLSI) guidelines. Three lots of custom-made frozen 96-well polystyrene microtiter plates were used and prepared with 2* prediluted drugs in 7H9 broth-oleic acid albumin dextrose catalase. The QC reference strain was Mycobacterium tuberculosis H37Rv. MIC frequency, mode, and geometric mean were calculated for each drug. QC ranges were derived based on predefined, strict CLSI criteria. Any data lying outside CLSI criteria resulted in exclusion of the entire laboratory data set. Data from one laboratory were excluded due to higher MIC values than other laboratories. QC ranges were established for 11 drugs: isoniazid (0.03 to 0.12 MUg/ml), rifampin (0.03 to 0.25 MUg/ml), ethambutol (0.25 to 2 MUg/ml), levofloxacin (0.12 to 1 MUg/ml), moxifloxacin (0.06 to 0.5 MUg/ml), ofloxacin (0.25 to 2 MUg/ml), amikacin (0.25 to 2 MUg/ml), kanamycin (0.25 to 2 MUg/ml), capreomycin (0.5 to 4 MUg/ml), linezolid (0.25 to 2 MUg/ml), and clofazimine (0.03 to 0.25 MUg/ml). QC ranges could not be established for nicotinamide (pyrazinamide surrogate), prothionamide, or ethionamide, which were assay nonperformers. Using strict CLSI criteria, QC ranges against the M. tuberculosis H37Rv reference strain were established for the majority of commonly used antituberculosis drugs, with a convenient 7H9 broth microdilution MIC method suitable for use in resource limited settings. PMID- 27654339 TI - High intraspecies heterogeneity within Staphylococcus sciuri and rejection of its classification into S. sciuri subsp. sciuri, S. sciuri subsp. carnaticus and S. sciuri subsp. rodentium. AB - A polyphasic taxonomic approach was applied to strains of the species Staphylococcus sciuri in order to clarify the taxonomic legitimacy of the delineation of S. sciuri into S. sciurisubsp.sciuri, S. sciurisubsp.carnaticus and S. sciurisubsp.rodentium. A group of 81 S. sciuri isolates obtained from human (n=62) and veterinary (n=17) clinical materials and foods (n=2) and ten reference and type strains obtained from the Czech Collection of Microorganisms were characterized by extensive biotyping using conventional tests and commercial identification kits (ID 32 Staph, STAPHYtest, Biolog Microbial ID System), matrix assisted laser-desorption/ionization time-of-flight mass spectrometry, automated ribotyping with EcoRI restriction enzyme, 16S-23S rRNA gene intergenic transcribed spacer PCR fingerprinting and repetitive sequence-based PCR fingerprinting with the (GTG)5 primer. Selected strains representing different ribotypes were further characterized using sequencing of the beta-subunit of RNA polymerase (rpoB) gene. Individual techniques revealed high heterogeneity within the analysed S. sciuri strains but differentiation of the investigated strains into groups corresponding to the aforementioned S. sciuri subspecies and supported by these techniques was not clearly revealed. Based on obtained results and data retrieved from literature we propose rejecting the separation of S. sciuri species into S. sciurisubsp.sciuri, S. sciurisubsp.carnaticus and S. sciurisubsp.rodentium and we suggest reclassification these subspecies as S. sciuri with the type strain W.E. Kloos SC 116T (=ATCC 29062T=BCRC 12927T=CCM 3473T=CCUG 15598T=CNCTC 5683T=DSM 20345T=JCM 2425T=NCTC 12103T). PMID- 27654340 TI - GRADE Methods for Guideline Development: Time to Evolve? PMID- 27654341 TI - Pain in the body. Altered interoception in chronic pain conditions: A systematic review. AB - Interoception is the sense of the physiological condition of the body. Modern definitions differentiated three separated sub-constructs: accuracy (IAc), i.e., the ability to detect physiological states, sensibility (IAs), i.e., a self evaluated measure of interoception, and awareness (IAw) i.e., a metacognitive awareness of the accuracy. Preliminary researches correlated pain with alterations in the interoceptive matrix albeit, to the best of our knowledge, interoceptive alterations in chronic pain conditions have never been studied systematically. We searched for studies that assessed interoception in subjects with chronic pain and compared it to healthy population. Eleven studies were included among different chronic pain conditions. Results suggested that chronic pain subjects might present low IAc and, allegedly, that IAc negatively correlates with symptoms severity in specific disorders. Data were inconclusive for IAs and IAw. The high risk of bias across multiple dimensions suggests to consider these conclusions with cautions. Nonetheless, deficits in interoceptive processes indicate a promising path for new form of therapies, and they require further attention and a more defined line of research. PMID- 27654342 TI - Junior doctors' strikes: BMA responds to your questions. PMID- 27654343 TI - Psychometric Evaluation of an Adolescent and Young Adult Module of the Impact of Cancer Instrument. AB - PURPOSE: To develop and evaluate a new instrument that measures unique aspects of long-term survivorship for people diagnosed with cancer as Adolescent and Young Adult (AYA), not measured by existing tools. METHODS: A new candidate instrument the Impact of Cancer for Adolescent and Young Adult (IOC-AYA) cancer survivors was developed and administered to AYA cancer survivors aged 18-35 years who were 15-29 years old when diagnosed with cancer. Psychometric properties of newly derived scales were assessed. RESULTS: Factor analyses of items derived seven new and specific subscales: Social Life; Uncertainties, Worries and Wonders; Cognitive Function; Sense of Purpose/Life Goals; Identity; Health Behaviors; and Health Literacy. Two separate and conditional subscales were formed: Relationship Concerns (partnered/unpartnered) and Having Children (at least one child/no children). Internal consistency measurements for these subscales ranged from 0.70 to 0.90. Expected associations within and among IOC-AYA subscales and standardized measures of quality of life were observed. CONCLUSION: Psychometric analyses indicated that this initial version of the IOC-AYA measures distinct and relevant constructs for survivors diagnosed with cancer in adolescence and young adulthood. Future work is needed to confirm the responsiveness to change and further validate the instrument in multiple and representative samples. Use of the IOC-AYA instrument in research and clinical practice will inform the development of psychosocial and supportive care interventions that not only minimize or prevent long-term deleterious effects of cancer but also promote positive adaptation, resilience, and the achievement of age-specific developmental tasks. PMID- 27654345 TI - A shape tailored gold-conductive polymer nanocomposite as a transparent electrode with extraordinary insensitivity to volatile organic compounds (VOCs). AB - In this study, the transparent conducting polymer of poly (3,4 ethylenendioxythiophene): poly(styrene sulphonate) (PEDOT:PSS) was nanohybridized via inclusion of gold nanofillers including nanospheres (NSs) and nanorods (NRs). Such nanocomposite thin films offer not only more optimum conductivity than the pristine polymer but also excellent resistivity against volatile organic compounds (VOCs). Interestingly, such amazing properties are achieved in the diluted regimes of the nanofillers and depend on the characteristics of the interfacial region of the polymer and nanofillers, i.e. the aspect ratio of the latter component. Accordingly, a shape dependent response is made that is more desirable in case of using the Au nanorods with a much larger aspect ratio than their nanosphere counterparts. This transparent nanocomposite thin film with an optimized conductivity and very low sensitivity to organic gases is undoubtedly a promising candidate material for the touch screen panel production industry. Considering PEDOT as a known material for integrated electrodes in energy saving applications, we believe that our strategy might be an important progress in the field. PMID- 27654344 TI - Point-of-Care Hemostatic Testing in Cardiac Surgery: A Stepped-Wedge Clustered Randomized Controlled Trial. AB - BACKGROUND: Cardiac surgery is frequently complicated by coagulopathic bleeding that is difficult to optimally manage using standard hemostatic testing. We hypothesized that point-of-care hemostatic testing within the context of an integrated transfusion algorithm would improve the management of coagulopathy in cardiac surgery and thereby reduce blood transfusions. METHODS: We conducted a pragmatic multicenter stepped-wedge cluster randomized controlled trial of a point-of-care-based transfusion algorithm in consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at 12 hospitals from October 6, 2014, to May 1, 2015. Following a 1-month data collection at all participating hospitals, a transfusion algorithm incorporating point-of-care hemostatic testing was sequentially implemented at 2 hospitals at a time in 1-month intervals, with the implementation order randomly assigned. No other aspects of care were modified. The primary outcome was red blood cell transfusion from surgery to postoperative day 7. Other outcomes included transfusion of other blood products, major bleeding, and major complications. The analysis adjusted for secular time trends, within-hospital clustering, and patient-level risk factors. All outcomes and analyses were prespecified before study initiation. RESULTS: Among the 7402 patients studied, 3555 underwent surgery during the control phase and 3847 during the intervention phase. Overall, 3329 (45.0%) received red blood cells, 1863 (25.2%) received platelets, 1645 (22.2%) received plasma, and 394 (5.3%) received cryoprecipitate. Major bleeding occurred in 1773 (24.1%) patients, and major complications occurred in 740 (10.2%) patients. The trial intervention reduced rates of red blood cell transfusion (adjusted relative risk, 0.91; 95% confidence interval, 0.85-0.98; P=0.02; number needed to treat, 24.7), platelet transfusion (relative risk, 0.77; 95% confidence interval, 0.68-0.87; P<0.001; number needed to treat, 16.7), and major bleeding (relative risk, 0.83; 95% confidence interval, 0.72-0.94; P=0.004; number needed to treat, 22.6), but had no effect on other blood product transfusions or major complications. CONCLUSIONS: Implementation of point-of-care hemostatic testing within the context of an integrated transfusion algorithm reduces red blood cell transfusions, platelet transfusions, and major bleeding following cardiac surgery. Our findings support the broader adoption of point-of-care hemostatic testing into clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02200419. PMID- 27654346 TI - Contrasting diets reveal metabolic plasticity in the tree-killing beetle, Anoplophora glabripennis (Cerambycidae: Lamiinae). AB - Wood-feeding insects encounter challenging diets containing low protein quantities, recalcitrant carbohydrate sources, and plant defensive compounds. The Asian longhorned beetle (Anoplophora glabripennis) is a wood-feeding insect that attacks and kills a diversity of hardwood tree species. We compared gene expression of midguts collected from larvae feeding in a preferred tree, sugar maple, to those consuming a nutrient-rich artificial diet, to identify genes putatively involved in host plant utilization. Anoplophora glabripennis larvae exhibited differential expression of ~3600 genes in response to different diets. Genes with predicted capacity for plant and microbial carbohydrate usage, detoxification, nutrient recycling, and immune-related genes relevant for facilitating interactions with microbial symbionts were upregulated in wood feeding larvae compared to larvae feeding in artificial diet. Upregulation of genes involved in protein degradation and synthesis was also observed, suggesting that proteins incur more rapid turnover in insects consuming wood. Additionally, wood-feeding individuals exhibited elevated expression of several mitochondrial cytochrome C oxidase genes, suggesting increased aerobic respiration compared to diet-fed larvae. These results indicate that A. glabripennis modulates digestive and basal gene expression when larvae are feeding in a nutrient-poor, yet suitable host plant compared to a tractable and nutrient-rich diet that is free of plant defensive compounds. PMID- 27654347 TI - Spheroidal Organoids Reproduce Characteristics of Longitudinal Depth Zones in Bovine Articular Cartilage. AB - Articular cartilage has multiple histologically distinct longitudinal depth zones. Development and pathogenesis occur throughout these zones. Cartilage explants, monolayer cell culture and reconstituted 3-dimensional cell constructs have been used for investigating mechanisms of pathophysiology in articular cartilage. Such models have been insufficient to reproduce zone-dependent cellular characteristics and extracellular matrix (ECM) upon investigation into cartilage development and pathogenesis. Therefore, we defined a chondrocyte spheroid model consistently formed with isolated chondrocytes from longitudinal depth zones without extrinsic materials. This spheroid showed zone-dependent characteristics of size, cartilage-specific ECM (collagen types I and II, aggrecan and keratan sulfate) and gene expressions of anabolic and catabolic molecules (matrix molecules and matrix metalloproteinase-13). In addition, the spheroid model is small enough to maintain the viability of cells and point symmetry to analyze the gradient of diffusive molecules. This spheroid organoid model will be useful to elucidate the mechanism of histogenesis and pathogenesis in articular cartilage. PMID- 27654349 TI - The origin of neutron biological effectiveness as a function of energy. AB - The understanding of the impact of radiation quality in early and late responses of biological targets to ionizing radiation exposure necessarily grounds on the results of mechanistic studies starting from physical interactions. This is particularly true when, already at the physical stage, the radiation field is mixed, as it is the case for neutron exposure. Neutron Relative Biological Effectiveness (RBE) is energy dependent, maximal for energies ~1 MeV, varying significantly among different experiments. The aim of this work is to shed light on neutron biological effectiveness as a function of field characteristics, with a comprehensive modeling approach: this brings together transport calculations of neutrons through matter (with the code PHITS) and the predictive power of the biophysical track structure code PARTRAC in terms of DNA damage evaluation. Two different energy dependent neutron RBE models are proposed: the first is phenomenological and based only on the characterization of linear energy transfer on a microscopic scale; the second is purely ab-initio and based on the induction of complex DNA damage. Results for the two models are compared and found in good qualitative agreement with current standards for radiation protection factors, which are agreed upon on the basis of RBE data. PMID- 27654348 TI - The temporally controlled expression of Drongo, the fruit fly homolog of AGFG1, is achieved in female germline cells via P-bodies and its localization requires functional Rab11. AB - To achieve proper RNA transport and localization, RNA viruses exploit cellular vesicular trafficking pathways. AGFG1, a host protein essential for HIV-1 and Influenza A replication, has been shown to mediate release of intron-containing viral RNAs from the perinuclear region. It is still unknown what its precise role in this release is, or whether AGFG1 also participates in cytoplasmic transport. We report for the first time the expression patterns during oogenesis for Drongo, the fruit fly homolog of AGFG1. We find that temporally controlled Drongo expression is achieved by translational repression of drongo mRNA within P bodies. Here we show a first link between the recycling endosome pathway and Drongo, and find that proper Drongo localization at the oocyte's cortex during mid-oogenesis requires functional Rab11. PMID- 27654350 TI - A New Chronology for Rhafas, Northeast Morocco, Spanning the North African Middle Stone Age through to the Neolithic. AB - Archaeological sites in northern Africa provide a rich record of increasing importance for the origins of modern human behaviour and for understanding human dispersal out of Africa. However, the timing and nature of Palaeolithic human behaviour and dispersal across north-western Africa (the Maghreb), and their relationship to local environmental conditions, remain poorly understood. The cave of Rhafas (northeast Morocco) provides valuable chronological information about cultural changes in the Maghreb during the Palaeolithic due to its long stratified archaeological sequence comprising Middle Stone Age (MSA), Later Stone Age (LSA) and Neolithic occupation layers. In this study, we apply optically stimulated luminescence (OSL) dating on sand-sized quartz grains to the cave deposits of Rhafas, as well as to a recently excavated section on the terrace in front of the cave entrance. We hereby provide a revised chronostratigraphy for the archaeological sequence at the site. We combine these results with geological and sedimentological multi-proxy investigations to gain insights into site formation processes and the palaeoenvironmental record of the region. The older sedimentological units at Rhafas were deposited between 135 ka and 57 ka (MIS 6 MIS 3) and are associated with the MSA technocomplex. Tanged pieces start to occur in the archaeological layers around 109 ka, which is consistent with previously published chronological data from the Maghreb. A well indurated duricrust indicates favourable climatic conditions for the pedogenic cementation by carbonates of sediment layers at the site after 57 ka. Overlying deposits attributed to the LSA technocomplex yield ages of ~21 ka and ~15 ka, corresponding to the last glacial period, and fall well within the previously established occupation phase in the Maghreb. The last occupation phase at Rhafas took place during the Neolithic and is dated to ~7.8 ka. PMID- 27654352 TI - Editorial. AB - SHOULD RAPISTS ever be restored to the register? Most people would say no. Indeed, over 90 per cent of nurses at this year's Royal College of Nursing Congress voted in favour of a resolution to ban nurses convicted of rape and other serious offences from nursing for life. The question is - do the proposals that the UKCC have devised and are most likely to be approved at this week's Council meeting go far enough in protecting patients and nursing's reputation? PMID- 27654351 TI - Corrigendum: Mammalian Mon2/Ysl2 regulates endosome-to-Golgi trafficking but possesses no guanine nucleotide exchange activity toward Arl1 GTPase. PMID- 27654353 TI - Proposed rules fall short of permanent ban on convicts. AB - NEW RULES drawn up after convicted rapist Yuen How Choy was restored to the nursing register will be considered by the UK Central Council (UKCC) this week. PMID- 27654354 TI - Opinion still split over composition of UKCC for next term of office. AB - The consultation exercise on the make up of the UKCC for its next term of office has brought no consensus on what the proportion of nurses, midwives and health visitors should be. PMID- 27654355 TI - Antenatal care row continues. AB - The UKCC's bid to clear up controversy over practice nurses giving antenatal care has failed to settle differences between nurses and midwives. PMID- 27654356 TI - Fury as second trust moves to a 'generic worker' scheme. AB - Nursing unions are furious at plans by a second NHS trust to use cleaners for nursing tasks. PMID- 27654358 TI - Inadequate information leads to baby milk scare. AB - Nursing unions have attacked the government for failing to give health practitioners and the public adequate information about whether some brands of baby milk formulae contain contarminants. PMID- 27654357 TI - ? AB - Bikini bare: TV presenter Toyah Wilcox with the bikini condom, once used in America and now just one of the items on display at the History of Contraception Museum, which opened in London last week. Other rare and unusual exhibits include crocodile dung, weasels' testicles and bones, a wooden pessary, and lucky charms, such as mules' ear wax and a bone taken from the right side of a totally black cat. PMID- 27654359 TI - It's time Gary the guide dog had his day, says College steward. AB - A nurse is calling for a guide dog to be made an honorary member of the Royal College of Nursing. PMID- 27654362 TI - Nominations requested for RCN posts. AB - Nominations for the next RCN president, deputy president and student member of Council are now being requested. PMID- 27654360 TI - Ancillaries to get pay rise denied to nurses. AB - Nurses at an Essex trust have been told they will get nothing to top up the 2 per cent national pay award, so that low pay among ancillary staff can be tackled. PMID- 27654363 TI - Extended roles need national standards. AB - NATIONAL STANDARDS and qualifications are urgently required for nurses in extended roles, the Association of Surgeons annual meeting was told. PMID- 27654364 TI - On the move. AB - Promotions / new appointments. PMID- 27654365 TI - Depressed older people not getting proper care. AB - A STUDY of older people receiving home care found almost half of them had a mental disorder and many were not getting appropriate treatment. PMID- 27654367 TI - US nurses help terminally ill patients to die. AB - ONE IN FIVE intensive care nurses in the United States have intentionally hastened the death of a terminally ill patient without telling the patient's doctor, says a report in The New England Journal of Medicine. PMID- 27654366 TI - ? AB - No sucker: Unison general secretary Rodney Bickerstaffe joined in at a celebration to mark the union's sponsorship of the National Jazz Youth Orchestra, which will receive L35,000 over the next three years. PMID- 27654368 TI - Government cuts funds for breast cancer screening in older women. AB - FUNDING FOR breast cancer screening for women over 65 was cut by 40 per cent last year, according to figures discovered by the chair of the parliamentary all-party breast cancer group. PMID- 27654369 TI - More cash to train paediatric ITU nurses. AB - HEALTH secretary Stephen Dorrell is to make an extra L2 million available to train children's nurses in intensive care in time for the expected peak in demand this winter. PMID- 27654370 TI - ? AB - Nurses from Bradford Royal Infirmary joined Geoff Thompson, the BBC TV Good Morning self defence expert, in a workshop to learn how to use self defence skills to deal with aggressive patients. PMID- 27654371 TI - Joining a gun club helped my son. AB - I would like to offer my views on guns, following Mike Lehane's article (Opinion May 15). At the age of 13 my son Martin was, like many teenagers, aggressive and difficult at home and school. PMID- 27654372 TI - A&E nurses best for emergency patients. AB - After reading the article,'Heart to heart' (Features May 15) I congratulate Andrew Mooraby and his colleagues for demonstrating how the nurse's role can be developed to enhance patient care. PMID- 27654373 TI - Legal responsibility for midwives. AB - In 'Do birthplans empower women? A study of their views' (Art & Science April 24), Sooi-Ken Too states that in making a successful birthplan the woman 'retains autonomy for decision making and accepts responsibility for any decisions made'. PMID- 27654374 TI - Systematic reviews help practice. AB - The systematic review of the research on the preventative use of compression stockings by Dickson and her colleagues (Art & Science April 17) is to be welcomed. Nurses often do not have time to read the overwhelming amount of clinical research pertinent to their practice and this can detract from their ability to provide evidence- based health care. This article did much to demystify the analytic outcomes of recent research. PMID- 27654375 TI - Children have the right to play free from the perils of fouled parks and pavements. AB - I am so incensed by the report about the shortsighted view expressed by the RCN officer in Northern Ireland and her objection to the anti-dog fouling poster showing a boy squatting (News May 22). She's right about one tiling - it is an abuse of children, but only because they cannot play freely without getting dog muck on their shoes and on their hands They can't even tumble off their trikes without fear of dog excreta infecting a small graze. I applaud Lisburn council's poster. Sort out the real abuse of children and defend their right to play free of dog muck. PMID- 27654376 TI - Excellent service needs extra funding. AB - From reading the article 'Heart to heart', (Features May 15) it is apparent that this service is excellent. It was stated, however, that no cover is provided between 10pm and 7am, yet this is precisely the time when variation in circadian rhythms can prove responsible for chest pains and indeed acute myocardial infarction. Surely it is time extra funding was injected into this project and then perhaps other hospitals would adopt a similar response. PMID- 27654377 TI - The law and extended roles. AB - As someone working in practice development I have been involved in discussions regarding the use of the UKCC's Scope of Professional Practice and how it relates to certain aspects of midwifery practice. For example, topping up of epidurals and IV cannulation. PMID- 27654378 TI - ? AB - In October, the emergency admissions ward at Southampton general hospital is being moved to a new area and we are using the opportunity to re-think procedures. I have drawn up a short questionnaire consisting of yes and no answers concerning admission documentation and patients' length of stay. The questionnaire is already being piloted at one hospital. Would any trained staff working on an emergency admissions ward be willing to participate in our study? An SAE will be enclosed and information will be seen only by tine senior clinical nurses working on the unit. We hope to be able to publish some results of this survey later on. PMID- 27654379 TI - Sidelines. AB - Nurses with a flair for writing may have been tempted to combine their talents by becoming medical copywriters. But it would appear they would have no joy if they applied for a post at Lane, Earl & Cox, who describe themselves as 'one of the UK's leading healthcare advertising agencies, with a client list that's left the competition feeling pretty sick'. For their latest recruitment ad is headed 'Goat wanted for position of junior medical copywriter', and explains that a copy test will be set with the aim of separating the sheep from the goats. 'The goats will send back a copy test full of innovative, hard selling ideas and will be a pleasure to interview,' the ad concludes. 'The sheep will be sent a map of Wales.' PMID- 27654380 TI - Acting the scapegoat. AB - THE NATIONAL Health Service has seen the emergence of a new trend of 'customer relations', which has been accompanied by a rising number of complaints about its services. PMID- 27654382 TI - Readers Panel - A word for it. AB - Our experts consider a hot topic of the day. PMID- 27654381 TI - Divine intervention. AB - THE ROLE OF the hospital chaplain has had to change perhaps more them most in order to survive the NHS reforms. It is no longer enough to turn up on a ward beaming benignly, blessing everything that moves. PMID- 27654383 TI - The implementation and development of lecturer practitioner roles in nursing Judith Lathlean The implementation and development of lecturer practitioner roles in nursing Ashdale Press 205pp L12.95 1-870899-06-7 1870899067 [Formula: see text]. AB - In these clays of innovation, there are frequently too many fashions which are not subjected to tire rigour of academic scrutiny. Judith Lathlean, a highly respected academic, has subjected one such innovation - that of lecturer/practitioner (LP) - to a longitudinal indepth ethnographic study over three years and she has produced a fascinating insight into evolving roles in an evolving profession. PMID- 27654384 TI - Bank on it? AB - Traditionally, nurses working on the bank have been seen as nonemployees or self employed in that they have not been afforded the same employment rights, including statutory lights, in such matters as unfair dismissal and redundancy. PMID- 27654385 TI - Soundbites. AB - Quotable quotes from the world of health. PMID- 27654387 TI - Nurses' use of nonnecessary touch. AB - When and why do nurses and older patients use spontaneous touch? PMID- 27654386 TI - Treatment for radiation enteritis. AB - Hyperbaric oxygen might be useful for treating intestinal radiation injury, German researchers say. PMID- 27654388 TI - Nurses' attitudes to people with IBS. AB - Nurses hold negative attitudes towards people with irritable bowel syndrome (IBS) which can only be detrimental to a patient's treatment. PMID- 27654389 TI - Rheumatoid arthritis. PMID- 27654390 TI - Reply: Platelet noradrenaline uptake is unrelated to renal denervation. PMID- 27654391 TI - Reply: Platelet noradrenaline overload - cause of increased noradrenaline spillover in hypertension? PMID- 27654392 TI - Filarial nematode infection in eclectus parrots (Eclectus roratus) in Taiwan. AB - A total of 166 psittacines belonging to 22 species were received by the Animal Hospital of National Pingtung University of Science & Technology (NPUST) from 2013 to 2015. Only eclectus parrots (Eclectus roratus) were identified as hosts for microfilariae. All eclectus parrots were adult birds and had been kept in Taiwan for more than three years. The relevance of filariae to eclectus parrots is evident as indicated by the 35.7% (5/14) infection rate. At necropsy, adult filarial nematodes 57-75 mm in length and 0.4-0.7 mm in width were found in the hepatic veins. The microfilariae were 170-230 MUm in length. Histopathological examination confirmed that eggs and larvae were observed in the ovaries and uteri of female filariae. These nematodes were closely related to an unidentified Filaria sp. (KJ612514.1) as indicated by polymerase chain reaction (PCR) analysis and phylogenetic analysis of nucleotide sequences from 18S ribosomal DNA gene (18S rDNA), mitochondrial cytochrome c oxidase subunit 1 (COX1) gene, and internal transcribed spacers 1-5.8S ribosomal DNA gene (ITS 1-5.8S rDNA). However, structurally the filarial nematodes were similar to that of the Pelecitus sp. Eclectus parrot species are important pet birds and are highly traded, resulting in high uncertainty of the origin of the parasite infection. This study is the first of its kind to report the presence and potential impact of filarial nematode infection on eclectus parrots, suggesting parasite inspection prior to the international trade of these pet birds. PMID- 27654393 TI - Pyrazolo[1,5-a]pyridine-3-carboxamide hybrids: Design, synthesis and evaluation of anti-tubercular activity. AB - A series of pyrazolo[1,5-a]pyridine-3-carboxamide hybrids were designed and evaluated as novel anti-tubercular agents. The representative hybrid 7 exhibited promising in vitro activity against susceptive strain H37Rv and a panel of drug resistant Mtb strains with MIC values of 0.006 MUg/mL and ranged from 0.003 to 0.014 MUg/mL, respectively. More importantly, the hybrid 7 also showed very low cytotoxicity, and could significantly reduce the mycobacterial burden in a mouse model infected with autoluminescent H37Ra strain, which may serve as a lead compound for further development of new anti-tubercular agents. PMID- 27654394 TI - Fluorescein hydrazones: A series of novel non-intercalative topoisomerase IIalpha catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells. AB - Fluorescein hydrazones (5 and 7) were synthesized in three/four steps with 82-92% yields. All synthesized compounds were evaluated by topoisomerase I (topo I) and topoisomerase IIalpha (topo IIalpha)-mediated relaxation and cell viability assays. Among them, most of the compounds showed topo I & IIalpha inhibitory activity and nineteen compounds showed strong anti-proliferative activity against various cell lines. In brief, 5e inhibited 53% topo IIalpha (etoposide 29%) at 20 MUM and showed excellent antiproliferative activity against DU145 (1.43 +/- 0.04 MUM), HCT15 (2.4 +/- 0.03 MUM) and MCF7 (11.4 +/- 0.5 MUM) cell lines in comparison with adriamycin, etoposide, and camptothecin. Compounds 5e, 5g and 5h were further evaluated to determine their mode of action. Compounds 5e, 5g and 5h functioned as non-intercalative topo IIalpha catalytic inhibitor with induction of G1 arrest and activation of apoptotic proteins in dose-dependent manner. PMID- 27654395 TI - Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold. AB - From 4 antiplasmodial hit-molecules identified in 2-trichloromethylquinazoline series, we conducted a global Structure-Activity relationship (SAR) study involving 26 compounds and covering 5 molecular regions (I - V), aiming at defining the corresponding pharmacophore and identifying new bioactive derivatives. Thus, after studying the aniline moiety in detail, thienopyrimidine, quinoline and quinoxaline bio-isosters were synthesized and tested on the K1 multi-resistant P. falciparum strain, along with a cytotoxicity evaluation on the human HepG2 cell line, to define selectivity indecies. SARs first showed that thienopyrimidines and quinolines were globally more cytotoxic, while quinoxaline analogs appeared as active as- and less cytotoxic than their quinazoline counterparts. Such pharmacomodulation in quinoxaline series not only provided a new antiplasmodial reference hit-molecule (IC50 = 0.4 MUM, selectivity index = 100), but also highlighted an active (IC50 = 0.4 MUM) and quite selective (SI = 265) synthesis intermediate. PMID- 27654397 TI - Predominant cause of prolonged low-frequency force depression changes during recovery after in situ fatiguing stimulation of rat fast-twitch muscle. AB - To investigate time-dependent changes in sarcoplasmic reticulum (SR) Ca2+ release and myofibrillar (my-) Ca2+ sensitivity during recovery from prolonged low frequency force depression (PLFFD), rat gastrocnemius muscles were electrically stimulated in situ. After 0 h (R0), 0.5 h (R0.5), 2 h (R2), 6 h (R6), or 12 h of recovery, the superficial gastrocnemius muscles were excised and used for biochemical and skinned fiber analyses. At R0, R0.5, R2, and R6, the ratio of force at 1 Hz to that at 50 Hz was decreased in the skinned fibers. The ratio of depolarization-induced force to the maximum Ca2+-activated force (depol/Ca2+ force ratio) was utilized as an indicator of SR Ca2+ release. At R0, both the depol/Ca2+ force ratio and my-Ca2+ sensitivity were decreased. At R0.5 and R2, my Ca2+ sensitivity was recovered, while the depol/Ca2+ force ratio remained depressed. At R6, my-Ca2+ sensitivity was decreased again, whereas the depol/Ca2+ force ratio was nearly restored. Western blot analyses demonstrated that decreased my-Ca2+ sensitivity at R6 and reduced depol/Ca2+ force ratio at R0, R0.5, and R2 were accompanied by depressions in S-glutathionylated troponin I and increases in dephosphorylated ryanodine receptor 1, respectively. These results indicate that, in the early stage of recovery, reduced SR Ca2+ release plays a primary role in the etiology of PLFFD, whereas decreased my-Ca2+ sensitivity is involved in the late stage, and suggest that S-glutathionylation of troponin I and dephosphorylation of ryanodine receptor 1 contribute, at least partly, to fatiguing contraction-induced alterations in my-Ca2+ sensitivity and SR Ca2+ release, respectively. PMID- 27654398 TI - Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope. AB - Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 +/- 5.0 yr) and 15 matched controls (22.8 +/- 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ~40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS. PMID- 27654399 TI - Cholinergic and beta-adrenergic control of cardiovascular reflex responses to brief repeated asphyxia in term-equivalent fetal sheep. AB - The role of cholinergic and beta-adrenergic activity in mediating fetal cardiovascular recovery from brief repeated episodes of asphyxia consistent with established labor, remains unclear. In this study, we tested the effect of cholinergic and beta-adrenergic blockade on the fetal chemoreflex and fetal heart rate (FHR) overshoot responses during brief repeated asphyxia at rates consistent with early or active labor. Chronically instrumented fetal sheep at 0.85 of gestation received either i.v. atropine sulfate (cholinergic blockade, n=8) or vehicle (n=7) followed by 3 x 1-minute umbilical cord occlusions repeated every 5 minutes (1:5; consistent with early labor), or i.v. propranolol hydrochloride (beta-adrenergic blockade, n=6) or vehicle (n=6) followed by 3 x 2-minute occlusions repeated every 5 minutes (2:5; consistent with active labor). In vehicle-controls, 1:5 occlusions were associated with rapid and sustained FHR decelerations followed by rapid return of FHR to baseline values after release of the occlusion. Cholinergic blockade abolished FHR decelerations during occlusions and caused FHR overshoot after release of the occlusion (P<0.05 vs. control 1:5). In vehicle-controls, 2:5 occlusions caused rapid and sustained FHR decelerations followed by FHR overshoot after release of the occlusion. beta-adrenergic blockade was associated with greater reduction in FHR during occlusions and attenuated FHR overshoot (P<0.05 vs. control 2:5). These data demonstrate that the FHR overshoot pattern after asphyxia is mediated by a combination of attenuated parasympathetic activity and increased beta-adrenergic stimulation of the fetal heart. PMID- 27654400 TI - International Journal of Psychiatry in Clinical Practice. PMID- 27654396 TI - Maternal Western diet increases adiposity even in male offspring of obesity resistant rat dams: early endocrine risk markers. AB - Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. PMID- 27654401 TI - Relationship between impulsivity and obsession types in obsessive-compulsive disorder. AB - OBJECTIVE: Impulsivity is an important aspect of obsessive-compulsive disorder (OCD) which is classified under a new heading in DSM-5 with other impulsivity related disorders like trichotillomania. Due to its heterogeneous nature, different obsessions may be linked to varying impulsivity profiles. Aim of this study was to investigate the impulsivity traits and their relationship with obsession types by comparing OCD subjects who display sexual, religious and aggressive obsessions or other obsessions to healthy controls. METHODS: Outpatients with OCD (n = 146) and healthy controls (n = 80) were evaluated with Sociodemographic Data Form, SCID-I, SCID non-patient version, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Barratt Impulsiveness Scale (BIS-11). RESULTS: BIS-11 attention scores of the OCD group were significantly higher than healthy subjects. In patients with sexual, aggressive, religious obsessions, BIS 11 attention scores were significantly higher than those who have other obsession types and that of controls. CONCLUSIONS: Higher levels of attentional impulsivity, particularly in patients suffering from sexual, aggressive or religious obsessions suggest a common diathesis for a dysfunction in neural correlates corresponding to these symptoms. The results of our study may promote further studies conducted with more advanced and objective neuropsychometric tests evaluating features of the clinical course, neurobiology and the response to OCD treatment. PMID- 27654402 TI - Early adolescents' motivations to defend victims in school bullying and their perceptions of student-teacher relationships: A self-determination theory approach. AB - The aim of this study was to investigate whether various dimensions of student teacher relationships were associated with different types of motivation to defend victims in bullying and to determine the association between these types of motivations and various bystander behaviors in bullying situations among early adolescents in Italy. Data were collected from 405 Italian adolescents who completed a survey in their classroom. Results showed that warm student-teacher relationships were positively associated with defending victims and with autonomous motivation to defend victims. In contrast, conflictual student-teacher relationships were positively associated with passive bystanding and with extrinsic motivation to defend victims. Different forms of motivation to defend were found to be mediators between student-teacher relationship qualities and bystander behaviors in school bullying. Our findings suggest that teachers should build warm and caring student-teacher relationships to enhance students' autonomous motivation to defend victims of bullying as well as their inclination to defend the victims in practice. PMID- 27654403 TI - Pneumonia: Features registered in autopsy material. AB - BACKGROUND: Despite improvements in clinical practice, pneumonia remains one of the leading causes of death worldwide. Pathologic findings from autopsy reports could provide more precise and valid data on characteristics of pneumonia patients. METHODS: We retrospectively reviewed autopsy reports of deceased patients admitted to the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica, Serbia, between 1994 and 2003. The patients were classified into two groups: group 1 (n = 161) comprised patients in whom pneumonia was the main cause of death, while group 2 (n = 165) consisted of patients in whom pneumonia was confirmed at autopsy but had various different causes of death. RESULTS: From 1776 patients who underwent autopsy 326 (18.3%) were diagnosed with pneumonia. The most common underlying diseases were atherosclerosis (29.4%), chronic obstructive pulmonary disease (COPD) (26.7%), and malignancies (20.2%). Pneumonia was the main cause of death in 161 cases (group 1) while in group 2 major causes of death were heart failure (HF) (26.7%), acute myocardial infarction (AMI) (16.4%), and pulmonary embolism (PE) (10.9%). Multilobar involvement (91% vs.27%), pulmonary effusion (29% vs.14%), and lung abscess (23.6% vs.8.5%) were more frequently found in group 1, compared to group 2. CONCLUSION: In patients with pneumonia who underwent autopsy most common underlying diseases were atherosclerosis, COPD, and malignancies, while major causes of death were: progression of pneumonia, HF, AMI, and PE. PMID- 27654404 TI - Public health facility resource availability and provider adherence to first antenatal guidelines in a low resource setting in Accra, Ghana. AB - BACKGROUND: Lack of resources has been identified as a reason for non-adherence to clinical guidelines. Our aim was to describe public health facility resource availability in relation to provider adherence to first antenatal visit guidelines. METHODS: A cross-sectional analysis of the baseline data of a prospective cohort study on adherence to first antenatal care visit guidelines was carried out in 11 facilities in the Greater Accra Region of Ghana. Provider adherence was studied in relation to health facility resource availability such as antenatal workload for clinical staffs, routine antenatal drugs, laboratory testing, protocols, ambulance and equipment. RESULTS: Eleven facilities comprising 6 hospitals (54.5 %), 4 polyclinics (36.4 %) and 1 health center were randomly sampled. Complete provider adherence to first antenatal guidelines for all the 946 participants was 48.1 % (95 % CI: 41.8-54.2 %), varying significantly amongst the types of facilities, with highest rate in the polyclinics. Average antenatal workload per month per clinical staff member was higher in polyclinics compared to the hospitals. All facility laboratories were able to conduct routine antenatal tests. Most routine antenatal drugs were available in all facilities except magnesium sulphate and sulphadoxine-pyrimethamine which were lacking in some. Antenatal service protocols and equipment were also available in all facilities. CONCLUSION: Although antenatal workload varies across different facility types in the Greater Accra region, other health facility resources that support implementation of first antenatal care guidelines are equally available in all the facilities. These factors therefore do not adequately account for the low and varying proportions of complete adherence to guidelines across facility types. Providers should be continually engaged for a better understanding of the barriers to their adherence to these guidelines. PMID- 27654405 TI - Simulating the Function of the MjNhaP1 Transporter. AB - The structures of transport proteins have been steadily revealed in the last few decades, and yet the conversion of this information into molecular-level understanding of their function is still lagging behind. In this study, we try to elucidate how the action of the archaeal sodium/proton antiporter MjNhaP1 depends on its structure-energy relationship. To this end, we calculate the binding energies of its substrates and evaluate the conformational change barrier, focusing on the rotation of the catalytic residue D161. We find that sodium ions and protons compete against a common binding site and that the accessibility of this binding site is restricted to either the inside or outside of the cell. We suggest that the rotation of D161 chi1 angle correlates with the conformational change and is energetically unfavorable when D161 does not bind any substrate. This restriction ensures coupling between the sodium ions and the protons, allowing MjNhaP1 and probably other similar transporters to exchange substrates with minimal leak. Using Monte Carlo simulations we demonstrate the feasibility of our model. Overall we present a complete picture that reproduces the electroneutral (at 1:1 substrate ratio) and coupled transport activity of MjNhaP1 including the energetic basis for the criteria provided by Jardetzky half a century ago. PMID- 27654406 TI - Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management. AB - Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery. PMID- 27654408 TI - Glaucoma Diagnostic Ability of Layer-by-Layer Segmented Ganglion Cell Complex by Spectral-Domain Optical Coherence Tomography. AB - Purpose: To evaluate the diagnostic ability of layer-by-layer segmented macular ganglion cell complex (GCC) using spectral-domain optical coherence tomography (OCT) for detection of glaucoma and to analyze the topographic patterns of the segmented thicknesses in open-angle glaucoma. Methods: Seventy-seven open-angle glaucoma patients and 59 healthy subjects were enrolled in this cross-sectional study. Spectral-domain OCT with automated segmentation was used to measure the separate thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). We compared the specific diagnostic abilities of the GCC (RNFL+GCL+IPL), ganglion cell-inner plexiform layer (GCIPL: GCL+IPL), and circumpapillary RNFL (cpRNFL) to discriminate between normal eyes and glaucoma. Results: The mRNFL, GCL, IPL, and cpRNFL thicknesses in glaucoma patients were all significantly thinner compared with healthy subjects and showed different topographic patterns. The GCC, mRNFL, and GCL thicknesses were best able to discriminate between the glaucoma and normal groups. The areas under the curve of receiver operating characteristics (AUROCs) of the mRNFL and GCL did not show significant difference from that of the cpRNFL. The AUROC of the GCL did not show significant difference from that of GCIPL after Bonferroni correction. The global IPL thickness had the smallest AUROC and showed lower diagnostic performance than the GCL, GCIPL, and GCC. Conclusions: The diagnostic ability of segmented mRNFL and GCL to discriminate between normal and glaucoma eyes is high and comparable to that of cpRNFL thickness. The measurement and monitoring of GCL could be a practical and effective approach to glaucoma diagnostics. PMID- 27654407 TI - Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning. AB - Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection. PMID- 27654409 TI - Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease. AB - Purpose: To assess whether tear hyperosmolarity, being diagnostic of dry eye disease (DED), is associated with specific alterations to the cytokine content of human tears that may provide a biomarker for DED. Methods: In this prospective, cross-sectional, clinical study, participants (n = 77) were recruited from a single clinical site and categorized into groups based upon tear osmolarity status (n = 62 hyperosmolar, n = 15 normo-osmolar). Comprehensive anterior eye clinical assessments were undertaken. Concentrations of seven cytokines (IL-2, IL 4, IL-6, IL-10, IL-17A, IFN-gamma, and TNF-alpha) in basal tears were assayed using multiplex cytometric bead array. The main outcome measure was difference in cytokine concentration between groups. Group comparisons were undertaken using 2 tailed t-tests. Cohen's effect size was calculated for each finding. Spearman correlations between cytokine concentrations, clinical symptoms, and clinical parameters of DED were calculated. Results: Tear hyperosmolarity was specifically associated with increased tear IFN-gamma levels (13.3 +/- 2.0 vs. 4.4 +/- 1.4 pg/mL, P = 0.03). Cohen's effect size was large (0.8) for changes to tear IFN gamma levels. Significant correlations were observed between IFN-gamma concentration and each of: tear osmolarity (r = 0.34; P = 0.007), total ocular surface staining (r = 0.56, P < 0.0001), and Schirmer test score (r = -0.33, P = 0.003). Conclusions: Tear hyperosmolarity is specifically associated with higher levels of the proinflammatory cytokine IFN-gamma, which correlate with key clinical parameters of DED. The calculated effect size (0.8) suggests that this assay has diagnostic power as a biomarker for evaporative DED. PMID- 27654410 TI - Assessment of Transepidermal Water Loss From the Ocular Area in Dry Eye Disease. AB - Purpose: To investigate transepidermal water loss (TEWL) from the ocular area in dry eye disease (DED) and evaluate the correlation between ocular TEWL and other DED parameters. Methods: Transepidermal water loss from the ocular area in 56 eyes with DED and 38 healthy eyes was measured using a Tewameter TM300 that was equipped with custom made goggles (measuring temperature 24 degrees C-26 degrees C and relative humidity 35%-45%). The DED group was classified into two subgroups, aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE). Correlations between ocular TEWL and other DED parameters, such as tear osmolarity, tear break-up time (TBUT), corneal staining, conjunctival staining, Schirmer I test, Ocular Surface Disease Index (OSDI), and Visual Analogue Scale score were evaluated. Results: Ocular TEWL was significantly higher in the DED group (63.0 +/- 12.2 g/h/m2) than in the control group (54.7 +/- 14.2 g/h/m2; P = 0.003). Although there was no significant difference, TEWL was higher in the ADDE subgroup (64.0 +/- 10.7 g/h/m2) compared with the EDE subgroup (61.1 +/- 14.9 g/h/m2). Tear break-up time, corneal staining score, and OSDI were significantly correlated with ocular TEWL (P < 0.05) in all participants. Ocular TEWL loss was negatively correlated with Schirmer I test value in the DED group. Conclusions: Ocular TEWL was significantly higher in DED patients compared with controls, reflecting higher tear evaporation in DED patients. Patients who have shorter Schirmer I test values tend to have higher TEWL values. Not only EDE but also ADDE patients may have increased tear evaporation. PMID- 27654411 TI - Complexity of the Class B Phenotype in Autosomal Dominant Retinitis Pigmentosa Due to Rhodopsin Mutations. AB - Purpose: Previously, patients with RHO mutations and a class A phenotype were found to have severe early-onset loss of rod function, whereas patients with a class B phenotype retained rod function at least in certain retinal regions. Here class B patients were studied at different disease stages to understand the topographic details of the phenotype in preparation for therapies of this regionalized retinopathy. Methods: A cohort of patients with RHO mutations and class B phenotype (n = 28; ages 10-80 years) were studied with rod and cone perimetry and optical coherence tomography (OCT). Results: At least three components of the phenotype were identified in these cross-sectional studies. Patients could have hemifield dysfunction, pericentral loss of function, or a diffuse rod sensitivity loss across the visual field. Combinations of these different patterns were also found. Colocalized photoreceptor layer thicknesses were in agreement with the psychophysical results. Conclusions: These disorders with regional retinal variation of severity require pre-evaluations before enrollment into clinical trials to seek answers to questions about where in the retina would be appropriate to deliver focal treatments, and, for retina-wide treatment strategies, where in the retina should be monitored for therapeutic efficacy (or safety). PMID- 27654412 TI - Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin. AB - Purpose: We determined whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration. Methods: Using an animal model of Pelizaeus-Merzbacher disease (shp) bilateral longitudinal measurements of the peripapillary RNFL (spectral domain OCT), electroretinograms (ERG), and visual evoked potentials (VEP) were performed in affected and control animals from 5 months to 2 years and in individual animals at single time points. Light and electron microscopy of the optic nerve and retina and histomorphometric measurements of the RNFL were compared to OCT data. Results: Of the shp animals, 17% had an average reduction of OCT RNFL thickness on the superior retinal quadrant compared to controls (P < 0.05). Electroretinograms showed normal photopic A- and B-waves but flash VEPs were disorganized in shp animals. Morphologically, the shp retinas and optic nerves revealed significant RNFL thinning (P < 0.001) without retinal ganglion cell (RGC) loss, decrease total and relative retinal axonal area, and loss of optic nerve axons. There was strong positive correlation between OCT and morphometric RNFL thickness measurements (r = 0.878, P = 0.004). Conclusion: The loss of optic nerve axons demonstrated in the shp model resulted in moderate thinning of the RNFL confirmed by OCT and histology. These results indicate that OCT-derived RNFL measurement can be a useful surrogate biomarker of optic nerve axon loss and potentially disease progression in demyelinating diseases. PMID- 27654414 TI - Characterization of Antigen-Presenting Macrophages and Dendritic Cells in the Healthy Human Sclera. AB - Purpose: The sclera is mainly made of collagen and fibroblasts. The aim of this study was to analyze whether immune cells are present in the healthy human sclera. Methods: Ten human anterior episcleral or stromal tissue samples from globe donors were immunohistochemically examined using confocal microscopy. The expression of the macrophage markers CD68, CD163 and CD11b, CD45 (a general leukocyte marker), MHCII (expressed by antigen-presenting cells [APCs]), CD11c (dendritic cell marker), lymphatic endothelium hyaluronan receptor-1 (LYVE1; expressed on lymphatic endothelium and macrophage subsets), chemokine receptor 7 (CCR7, a homing receptor for leukocytes), CXCL12 (expressed by activated leukocytes), CCR2 (a marker for inflammatory monocytes), and glial fibrillary acidic protein (GFAP; expressed by astrocytes) was analyzed and quantified. Results: In the episclera, a high number of cells (>=40 cells/mm2) were immunoreactive for CD68, CD45, MHCII, CCR7, LYVE1, and CD11b. Lower numbers (<20 cells/mm2) were positive for CXCL12, CCR2, and GFAP. The episclera showed a significantly higher number of cells compared to the stroma (P = 0.008). MHCII+ cells could be double positive for CCR7, CD45, CD11c, or CD11b and seldom CXCL12. Macrophages were most likely from the M1 type (CD68+, CD163-). Conclusions: The healthy human sclera contains several macrophage populations, which can function as APCs, with the highest density being present in the episclera. Most cells express macrophage markers and may function as APCs. The presence of these cells might indicate that scleral immune cells are important for maintaining physiological functions in the eye and may potentially contribute to blood vessel homeostasis. PMID- 27654413 TI - Shape Changes of the Anterior Lamina Cribrosa in Normal, Ocular Hypertensive, and Glaucomatous Eyes Following Acute Intraocular Pressure Elevation. AB - Purpose: The purpose of this study was to estimate and compare changes in anterior lamina cribrosa (LC) morphology in normal, ocular hypertensive (OHT), and glaucomatous eyes following acute elevations in intraocular pressure (IOP). Methods: The optic nerve heads (ONHs) of 97 subjects (17 OHT, 19 primary open angle glaucoma [POAG], 31 primary angle-closure glaucoma [PACG], and 30 normal subjects) were imaged using optical coherence tomography (OCT). Intraocular pressure was raised twice by applying forces to the anterior sclera, using an ophthalmodynamometer. After each IOP elevation, IOP was held constant and measured; each ONH was rescanned with OCT. In each OCT volume, the anterior LC was enhanced, delineated, and its global shape index (GSI) calculated and compared across groups. Results: The baseline IOP was 17.5 +/- 3.5 mm Hg and was increased to 38 +/- 5.9 mm Hg and then to 46.5 +/- 5.9 mm Hg. At the first IOP increment, mean GSI was significantly smaller than that at baseline in normal subjects and glaucoma subjects (P < 0.05) but not in OHT subjects (P = 0.12). For the second IOP increment, the mean GSI was significantly smaller than that at baseline in normal subjects and in OHT eyes (P < 0.05). After adjusting for age, sex, and baseline IOP, the LC of POAG eyes was found to be significantly more posteriorly curved than that of normal subjects (P = 0.04). Conclusions: Acute IOP elevations altered anterior LC shape in a complex nonlinear fashion. The LC of POAG eyes was more cupped following acute IOP elevations compared to that of normal subjects. PMID- 27654417 TI - Comparison of Several Parameters in Two Optical Coherence Tomography Systems for Detecting Glaucomatous Defects in High Myopia. AB - Purpose: To compare the diagnostic powers of parameters of the RTVue and Cirrus HD optical coherence tomography (OCT) systems in detecting glaucoma in highly myopic eyes. Methods: For this study, 28 glaucoma patients with high myopia (HM G) and 28 high-myopia controls (HM-C) were enrolled. The circumpapillary retinal nerve fiber layer (cp-RNFL) and ganglion cell complex (GCC) parameters in the RTVue-OCT, and the ganglion cell-inner plexiform layer (GCIPL) and cp-RNFL parameters in the Cirrus HD-OCT, were obtained for each subject. The receiver operating characteristics curve (ROC) was used to assess the diagnostic ability of each parameter, and the areas under the curves (AUROCs) of those parameters were compared. Results: In both OCTs, the macular parameters showed significantly higher diagnostic power than the cp-RNFL thickness. The minimum GCIPL (0.977), inferotemporal GCIPL (0.947), and vertical cup/disc (C/D) ratio (0.968) showed the best performances among all of the Cirrus HD-OCT parameters. The focal loss volume (FLV) (0.964), global loss volume (GLV) (0.899), and vertical C/D ratio (0.899) showed the best performances among all of the RTVue-OCT parameters. Among the parameters with high diagnostic ability in each protocol of the two OCTs, the superior sector of the cp-RNFL had significantly lower abilities than the FLV and the minimum of the GCIPL (P < 0.05) in detecting glaucoma in high myopia. Conclusions: The macular measurements had significantly better glaucoma detection abilities than the cpRNFL thickness in the high-myopia subjects in both RTVue-OCT and Cirrus HD-OCT, with no significant differences in the diagnostic ability between the two macular parameters. PMID- 27654415 TI - Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia. AB - Purpose: Increases in retinaldehyde dehydrogenase 2 (RALDH2) transcript in the chick choroid suggest that RALDH2 may be responsible for increases observed in all-trans-retinoic acid (atRA) synthesis during recovery from myopic defocus. The purpose of the present study was to examine RALDH2 protein expression, RALDH activity, and distribution of RALDH2 cells in control and recovering chick ocular tissues. Methods: Myopia was induced in White Leghorn chicks for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of RALDH isoforms in chick ocular tissues was evaluated by Western blot. Catalytic activity of RALDH was measured in choroidal cytosol fractions using an in vitro atRA synthesis assay together with HPLC quantification of synthesized atRA. Distribution of RALDH2 cells throughout the choroid was evaluated by immunohistochemistry. Results: RALDH2 was expressed predominately in the chick choroid (P < 0.001) and increased after 24 hours and 4 days of recovery (76%, 74%, and 165%, respectively; P < 0.05). Activity of RALDH was detected solely in the choroid and was elevated at 3 and 7 days of recovery compared to controls (70% and 48%, respectively; P < 0.05). The number of RALDH2 immunopositive cells in recovering choroids was increased at 24 hours and 4 to 15 days of recovery (P < 0.05) and were concentrated toward the RPE side compared to controls. Conclusions: The results of this study suggest that RALDH2 is the major RALDH isoform in the chick choroid and is responsible for the increased RALDH activity seen during recovery. PMID- 27654416 TI - Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy. AB - Purpose: The role of R-Ras in retinal angiogenesis and vascular permeability was evaluated in an oxygen-induced retinopathy (OIR) model using R-Ras knockout (KO) mice and in human diabetic neovascular membranes. Methods: Mice deficient for R Ras and their wild-type (WT) littermates were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. At P17 retinal vascularization was examined from whole mounts, and retinal vascular permeability was studied using Miles assay. Real-time RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of R-Ras in retina during development or in the OIR model. The degree of pericyte coverage and vascular endothelial (VE)-cadherin expression on WT and R-Ras KO retinal blood vessels was quantified using confocal microscopy. The correlation of R-Ras with vascular endothelial growth factor receptor 2 (VEGFR2) and human serum albumin on human proliferative diabetic retinopathy membranes was assessed using immunohistochemistry. Results: In retina, R-Ras expression was mostly restricted to the vasculature. Retinal vessels in the R-Ras KO mice were significantly more permeable than WT controls in the OIR model. A significant reduction in the direct physical contact between pericytes and blood vessel endothelium as well as reduced VE-cadherin immunostaining was found in R-Ras-deficient mice. In human proliferative diabetic retinopathy neovascular membranes, R-Ras expression negatively correlated with increased vascular leakage and expression of VEGFR2, a marker of blood vessel immaturity. Conclusions: Our results suggest that R-Ras has a role in controlling retinal vessel maturation and stabilization in ischemic retinopathy and provides a potential target for pharmacologic manipulation to treat diabetic retinopathy. PMID- 27654418 TI - Combination of Carboplatin and Bevacizumab Is an Efficient Therapeutic Approach in Retinoblastoma Patient-Derived Xenografts. AB - Purpose: Retinoblastoma (Rb) is a rare childhood cancer of the retina with a survival rate of 95% in children living in high-income countries, after appropriate therapies such as chemotherapy, local ophthalmologic treatment, and radiotherapy. However, due to inactivation of the RB1 gene, all bilateral and almost 15% of unilateral retinoblastoma patients have a higher risk of s econdary cancers, especially sarcomas. Hence, new nonmutagen treatments are warranted. Therefore, we investigated the efficacy of therapy using anti-VEGF antibody bevacizumab, either alone or with carboplatin, in well-characterized Rb patient derived xenografts (PDXs). Methods: Three Rb PDXs previously established and characterized, RB102, RB111, and RB200, have been treated using carboplatin, bevacizumab, or carboplatin + bevacizumab. In order to define antitumor responses, various quantitative PCR and histopathologic analyses have then been performed on tumors collected at the end of experiments. Results: In all treated PDX models, we have observed a high and significant improvement of chemotherapy induced in vivo efficacy by the antiangiogenic antibody. The overall response rate, lower than -0.5, was 48%, 27%, and 86% after carboplatin, bevacizumab, and carboplatin + bevacizumab, respectively (carboplatin versus carboplatin + bevacizumab; P < 10-2; bevacizumab versus carboplatin + bevacizumab; P < 10-3). In the Rb200 PDX, such a result was also observed when bevacizumab was combined with lower doses of carboplatin. Quantitative PCR and histopathologic analyses have been performed and confirmed the impact of the bevacizumab-based treatments on various angiogenic markers. Conclusions: Overall, our in vivo results confirm the interest in antiangiogenic therapy for the treatment of Rb in combination with carboplatin and provide a robust rationale for testing this combination in the clinical setting for Rb patients. PMID- 27654419 TI - Separate and Combined Effects of Hypoxia and Horizontal Bed Rest on Retinal Blood Vessel Diameters. AB - Purpose: To assess the separate and combined effects of exposure to prolonged and sustained recumbency (bed rest) and hypoxia on retinal microcirculation. Methods: Eleven healthy male subjects (mean +/- SD age = 27 +/- 6 years; body mass index [BMI] = 23.7 +/- 3.0 kg m-2) participated in a repeated-measures crossover design study comprising three 21-day interventions: normoxic bed rest (NBR; partial pressure of inspired O2, PiO2 = 133.1 +/- 0.3 mm Hg); hypoxic ambulation (HAMB; PiO2 = 90.0 +/- 0.4 mm Hg), and hypoxic bed rest (HBR; PiO2 = 90.0 +/- 0.4 mm Hg). Central retinal arteriolar (CRAE) and venular (CRVE) equivalents were measured at baseline and at regular intervals during each 21-day intervention. Results: Normoxic bed rest caused a progressive reduction in CRAE, with the change in CRAE relative to baseline being highest on day 15 (DeltaCRAE = -7.5 MUm; 95% confidence interval [CI]: -10.8 to -4.2; P < 0.0001). Hypoxic ambulation resulted in a persistent 21-day increase in CRAE, reaching a maximum on day 4 (DeltaCRAE = 9.4 MUm; 95% CI: 6.0-12.7; P < 0.0001). During HBR, the increase in CRAE was highest on day 3 (DeltaCRAE = 4.5 MUm; 95% CI: 1.2-7.8; P = 0.007), but CRAE returned to baseline levels thereafter. Central retinal venular equivalent decreased during NBR and increased during HAMB and HBR. The reduction in CRVE during NBR was highest on day 1 (DeltaCRVE = -7.9 MUm; 95 CI: -13.3 to -2.5), and the maximum DeltaCRVE during HAMB (24.6 MUm; 95% CI: 18.9-30.3) and HBR (15.2 MUm; 95% CI: 9.8-20.5) was observed on days 10 and 3, respectively. Conclusions: The diameters of retinal blood vessels exhibited a dynamic response to hypoxia and bed rest, such that retinal vasodilation was smaller during combined bed rest and hypoxia than during hypoxic exposure. PMID- 27654420 TI - Choroidal Structural Changes in Myopic Choroidal Neovascularization After Treatment With Antivascular Endothelial Growth Factor Over 1 Year. AB - Purpose: To evaluate choroidal structural changes in eyes with myopic choroidal neovascularization (mCNV) treated with anti-VEGF over 12 months. Methods: We prospectively evaluated subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) using spectral-domain optical coherence tomography (SD OCT) at baseline, 6, and 12 months in both eyes in patients presenting with unilateral mCNV. Choroidal vascularity index was defined as the ratio of luminal area to total choroidal area after SD-OCT images were binarized digitally. Results: We included 20 patients (20 eyes with mCNV and 20 fellow eyes without mCNV) with mean age of 60.35 +/- 10.85 years. At baseline, mean SFCT and CVI was similar between eyes with mCNV and fellow eyes (69.20 +/- 63.04 MUm vs. 67.10 +/- 65.74 MUm, P = 0.713 for SFCT and 59.44 +/- 3.92% vs. 59.03 +/-. 5.58%, P = 0.958 for CVI). Subfoveal choroidal thickness decreased significantly in the mCNV eyes to 54.75 +/- 45.43 MUm (P = 0.017) at 12 months after anti-VEGF therapy, whereas SFCT in the contralateral eyes did not change significantly. There was no significant change in CVI in mCNV eyes or contralateral eyes from baseline to 12 months. Thinning of SFCT did not influence final BCVA. Conclusions: Thinning of subfoveal choroid without alteration in CVI was observed in eyes with mCNV treated with anti-VEGF therapy over 12 months. This finding may be explained by mechanical stretching in response to globe expansion. PMID- 27654421 TI - Fractal Dimensional Analysis of Optical Coherence Tomography Angiography in Eyes With Diabetic Retinopathy. AB - Purpose: We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). Methods: A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. Results: The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 * 10-3) and deep (P = 2.653 * 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 * 10-5) and deep (P = 3.120 * 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. Conclusions: The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology. PMID- 27654422 TI - The Appearance of Phosphenes Elicited Using a Suprachoroidal Retinal Prosthesis. AB - Purpose: Phosphenes are the fundamental building blocks for presenting meaningful visual information to the visually impaired using a bionic eye device. The aim of this study was to characterize the size, shape, and location of phosphenes elicited using a suprachoroidal retinal prosthesis. Methods: Three patients with profound vision loss due to retinitis pigmentosa were implanted with a suprachoroidal electrode array, which was used to deliver charge-balanced biphasic constant-current pulses at various rates, amplitudes, and durations to produce phosphenes. Tasks assessing phosphene appearance, location, overlap, and the patients' ability to recognize phosphenes were performed using a custom psychophysics setup. Results: Phosphenes were reliably elicited in all three patients, with marked differences in the reported appearances between patients and between electrodes. Phosphene shapes ranged from simple blobs to complex forms with multiple components in both space and time. Phosphene locations within the visual field generally corresponded to the retinotopic position of the stimulating electrodes. Overlap between phosphenes elicited from adjacent electrodes was observed with one patient, which reduced with increasing electrode separation. In a randomized recognition task, two patients correctly identified the electrode being stimulated for 57.2% and 23% of trials, respectively. Conclusions: Phosphenes of varying complexity were successfully elicited in all three patients, indicating that the suprachoroidal space is an efficacious site for electrically stimulating the retina. The recognition scores obtained with two patients suggest that a suprachoroidal implant can elicit phosphenes containing unique information. This information may be useful when combining phosphenes into more complex and meaningful images that provide functional vision. PMID- 27654423 TI - Glial Endothelin-1 Regulates Retinal Blood Flow During Hyperoxia in Cats. AB - Purpose: To investigate the role of endothelin-1 (ET-1) in retinal glial cells in regulating retinal blood flow (RBF) during hyperoxia in cats. Methods: We measured the vessel diameter (D), blood velocity (V), and blood flow (F) simultaneously in first-order retinal arterioles using a laser Doppler velocimetry system. The animals were under general anesthesia during hyperoxia (100% oxygen) for 10 minutes 24 hours after intravitreal injection of L-2 aminoadipic acid (LAA), a gliotoxic compound, or diluted hydrochloric acid (0.01 N) used as the vehicle control. We also measured the changes in the RBF after intravitreal injection of BQ-123, a specific ET type A receptor antagonist, in LAA-treated eyes. To examine if endothelin-converting enzyme-1 (ECE-1), as an ET 1-generating enzyme located in retinal glial cells, immunohistochemical examinations with costaining of antiglial fibrillary acidic protein (GFAP) antibody and anti-ECE-1 antibody were performed in whole-mount retinas. Results: During hyperoxia, the decreases in D, V, and F in response to hyperoxia were attenuated significantly (P < 0.01 for all comparisons) in the LAA-treated eyes compared with the vehicle control (LAA, D, -8.5 +/- 1.5%; V, -13.8 +/- 1.5%; F, 27.8 +/- 3.0% versus vehicle control, D, -16.8 +/- 1.3%; V, -26.3 +/- 2.0%; F, 48.9 +/- 2.4%). In LAA-treated eyes, intravitreal injections of BQ-123 did not change the rate of hyperoxia-induced RBF compared to LAA-treated eyes. The anti ECE-1 antibody was costained with anti-GFAP antibody in the whole-mount retinas. Conclusions: The current findings suggest that retinal glial ET-1 may play an important role in regulating RBF during hyperoxia in cats. PMID- 27654425 TI - Erratum. PMID- 27654424 TI - The Antiproliferative Effect of Bevacizumab on Human Tenon Fibroblasts Is Not Mediated by Vascular Endothelial Growth Factor Inhibition. AB - Purpose: Vascular endothelial growth factor-signaling in human tenon fibroblasts (hTFs) has recently become a target for antifibrotic treatment in glaucoma filtration surgery. The anti-VEGF antibody bevacizumab (BVC) has been shown to increase filtration bleb size. Given the relatively high concentration of BVC needed to obtain an effect, we investigated whether BVC acts through VEGF inhibition or via non-antigen-dependent ways. Methods: Human tenon fibroblast primary cultures were obtained from strabismus surgery subjects. Under low (0.2%) and high (10%) serum conditions, cells were incubated with BVC, ranibizumab (RNB), aflibercept (AFB), or rituximab (RTX) at different concentrations. Total number of cells and number of dead or proliferating (5-bromo-2-deoxy-uridine positive) cells were assessed after 24 hours. Concentrations of VEGF-A in cell culture media was measured with ELISA. Intracellular IgG was detected with immunostaining and Western blot analysis. Results: In quiescent hTF culture (0.2% serum) the addition of 5 mg/mL BVC induced widespread cell death. Under proliferative conditions (10% serum), BVC reduced the number of proliferating cells. No such effect was observed with 2.5 mg/mL BVC or with 10 mg/mL AFB or 2.5 mg/mL RNB, although they were equally effective in binding free VEGF-A in the culture media. Instead, the CD20 antibody RTX, which did not bind VEGF, induced hTF death and inhibited proliferation in a BVC-comparable fashion. Bevacizumab, AFB, and RTX were detected intracellularly in a concentration-dependent manner. Conclusions: The cell death-inducing and antiproliferative effect of 5 mg/mL BVC appeared not to depend on VEGF inhibition. Our data question a direct role of VEGF for hTF survival and proliferation. PMID- 27654426 TI - Retinal Degeneration in Mice Deficient in the Lysosomal Membrane Protein CLN7. AB - Purpose: Neuronal ceroid lipofuscinoses comprise a genetically heterogeneous group of mainly childhood-onset neurodegenerative lysosomal storage disorders. Progressive loss of vision is among the typical clinical symptoms of these fatal disorders. Here, we performed a detailed analysis of retinal degeneration in mice deficient in the lysosomal membrane protein CLN7, a novel animal model of CLN7 disease. Methods: Immunohistochemical analyses of retinas at different ages were performed to qualitatively and quantitatively characterize retinal degeneration in CLN7-deficient mice. Storage material in mutant retinas was analyzed by electron microscopy, and expression levels of various lysosomal proteins were studied using immunohistochemistry, immunoblot analyses, and quantitative real time PCR. Results: We observed an early onset and rapidly progressing degeneration of photoreceptor cells in CLN7-deficient mice, resulting in the loss of more than 70% rod photoreceptors in 4-month-old animals. The number of cone photoreceptors was not detectably altered at this age. Loss of rod photoreceptors was accompanied by reactive astrogliosis and microgliosis. Immunohistochemical and immunoblot analyses revealed accumulation of subunit c of mitochondrial ATP synthase and saposin D in mutant retinas, and electron microscopic analyses demonstrated the presence of curvilinear bodies or fingerprint-like profiles in various cell types of CLN7-deficient retinas. We also found a marked dysregulation of various lysosomal proteins in mutant retinas. Conclusions: We conclude that the retina of CLN7-deficient mice represents a useful model to elucidate the pathomechanisms ultimately leading to neurodegeneration in CLN7 disease, and to evaluate the efficacy of strategies aimed at developing treatments for this fatal neurodegenerative lysosomal storage disorder. PMID- 27654427 TI - Reduction of the Lamina Cribrosa Curvature After Trabeculectomy in Glaucoma. AB - Purpose: To investigate whether the lamina cribrosa (LC) curvature is decreased after trabeculectomy. Methods: Thirty-nine eyes of 39 patients with primary open angle glaucoma who underwent trabeculectomy were included. Optic nerves were scanned by using enhanced-depth-imaging spectral-domain optical coherence tomography before and after trabeculectomy. The LC curvature was assessed by measuring the LC curvature index (LCCI) in seven horizontal B-scan images in each eye. Results: The LCCI was significantly smaller at postoperative 6 months than at the preoperative level in all seven planes (all P < 0.001). Preoperative LCCI was associated with younger age at superior midperiphery, midhorizontal plane, inferior midperiphery (all P <= 0.005) and higher preoperative intraocular pressure (IOP) at superior and inferior midperiphery (both P = 0.039). Younger age and larger preoperative LCCI were associated with a larger reduction of the LCCI at all three locations (P = 0.003 and 0.031 at superior midperiphery, P = 0.011 and 0.001 at midhorizontal plane, and P = 0.014 and 0.005 at inferior midperiphery, respectively), whereas the percentage IOP lowering was associated at superior and inferior midperiphery (P = 0.017 and 0.047, respectively). Conclusions: Lamina cribrosa curvature was reduced after trabeculectomy. This finding suggests that LC curvature may have value as a parameter relevant to optic nerve head biomechanics. PMID- 27654428 TI - Concurrent Investigation of Global Motion and Form Processing in Amblyopia: An Equivalent Noise Approach. AB - Purpose: Directly comparing the motion and form processing in neurologic disorders has remained difficult due to the limitations in the experimental stimulus. In the current study, motion and form processing in amblyopia was characterized using random dot stimuli in different noise levels to parse out the effect of local and global processing on motion and form perception. Methods: A total of 17 amblyopes (8 anisometropic and 9 strabismic), and 12 visually normal subjects monocularly estimated the global direction of motion and global orientation in random dot kinematograms (RDK) and Glass patterns (Glass), whose directions/orientations were drawn from normal distributions with a range of means and variances that served as external noise. Direction/orientation discrimination thresholds were measured without noise first then variance threshold was measured at the multiples of the direction/orientation threshold. The direction/orientation and variance thresholds were modelled to estimate internal noise and sampling efficiency parameters. Results: Overall, the thresholds for Glass were higher than RDK for all subjects. The thresholds for both Glass and RDK were higher in the strabismic eyes compared with the fellow and normal eyes. On the other hand, the thresholds for anisometropic amblyopic eyes were similar to the normal eyes. The worse performance of strabismic amblyopes was best explained by relatively low sampling efficiency compared with other groups (P < 0.05). Conclusions: A deficit in global motion and form perception was only evident in strabismic amblyopia. Contrary to the dorsal stream deficiency hypothesis assumed in other developmental disorders, deficits were present in both motion (dorsal) and form (ventral) processing. PMID- 27654430 TI - Letters. PMID- 27654429 TI - Heterozygous Pitx2 Null Mice Accurately Recapitulate the Ocular Features of Axenfeld-Rieger Syndrome and Congenital Glaucoma. AB - Purpose: The purpose of this analysis was to assess the utility of Pitx2+/- mice as a model for the ocular features of Axenfeld-Rieger Syndrome and for congenital glaucoma. Methods: Eyes of Pitx2+/- and wild-type littermates were examined clinically using optical coherence tomography (OCT) and fundus photography. Intraocular pressures were measured using a TonoLab rebound tonometer. Eyes were examined histologically to assess PITX2 expression, structural integrity, and optic nerve and ganglion cell content. Results: PITX2 is present postnatally in the corneal endothelium and stroma, iris stroma, trabecular meshwork, and Schlemm's canal. Reduced central corneal thickness, iris defects, and iridicorneal adhesions are all prevalent in Pitx2+/- eyes. Although optic nerve heads appear normal at postnatal day 7, IOP is elevated and optic nerve head cupping is fully penetrant in Pitx2+/- eyes by 3 weeks of age. Neurodegeneration is present in a significant percentage of optic nerves from Pitx2+/- mice by 3 weeks of age, and is fully penetrant by 2 months of age. Pitx2+/- eyes show significant reductions in specifically ganglion cell density in all four quadrants by 2 months of age. Conclusions: Pitx2+/- mice model the major ocular features of Axenfeld-Rieger Syndrome and will be an important resource for understanding the molecular mechanisms leading to anterior segment dysgenesis and a high prevalence of glaucoma in this disease. In addition, these mice may provide an efficient new model for assessing the molecular events in glaucoma more generally, and for developing and testing new treatment paradigms for this disease. PMID- 27654433 TI - Check your local listings. PMID- 27654435 TI - Conquering plagiarism in clinical practice. PMID- 27654434 TI - Preparing nurses to respond to in-house emergencies as a team. PMID- 27654436 TI - Semantic interoperability: The good, the bad, and the ugly. PMID- 27654438 TI - Diving deep into hyperbaric oxygen therapy. PMID- 27654439 TI - Evidence-based safe practice guidelines for I.V. push medications. PMID- 27654440 TI - Pain isn't always physical. PMID- 27654441 TI - Servant leadership: A model for emerging nurse leaders. PMID- 27654442 TI - Using a 3-question algorithm to interpret heart blocks. PMID- 27654443 TI - Nurses' most important role this flu season: Get vaccinated. PMID- 27654445 TI - The ethics of opioids for chronic noncancer pain. PMID- 27654444 TI - Amiodarone administration for refractory ventricular fibrillation or pulseless ventricular tachycardia. PMID- 27654446 TI - Today's nurses need genetics education. PMID- 27654447 TI - Online resources for opioid addiction. PMID- 27654449 TI - The Costs and Cost-effectiveness of Collaborative Care for Adolescents With Depression in Primary Care Settings: A Randomized Clinical Trial. AB - Importance: Depression is one of the most common adolescent chronic health conditions and can lead to increased health care use. Collaborative care models have been shown to be effective in improving adolescent depressive symptoms, but there are few data on the effect of such a model on costs. Objective: To evaluate the costs and cost-effectiveness of a collaborative care model for treatment of adolescent major depressive disorder in primary care settings. Design, Setting, and Participants: This randomized clinical trial was conducted between April 1, 2010, and April 30, 2013, at 9 primary care clinics in the Group Health system in Washington State. Participants were adolescents (age range, 13-17 years) with depression who participated in the Reaching Out to Adolescents in Distress (ROAD) collaborative care intervention trial. Interventions: A 12-month collaborative care intervention included an initial in-person engagement session, delivery of evidence-based treatments, and regular follow-up by master's level clinicians. Youth in the usual care control condition received depression screening results and could access mental health services and obtain medications through Group Health. Main Outcomes and Measures: Cost outcomes included intervention costs and per capita health plan costs, calculated from the payer perspective using administrative records. The primary effectiveness outcome was the difference in quality-adjusted life-years (QALYs) between groups from baseline to 12 months. The QALYs were calculated using Child Depression Rating Scale-Revised scores measured during the clinical trial. Cost and QALYs were used to calculate an incremental cost-effectiveness ratio. Results: Of those screened, 105 youths met criteria for entry into the study, and 101 were randomized to the intervention (n = 50) and usual care (n = 51) groups. Overall health plan costs were not significantly different between the intervention ($5161; 95% CI, $3564-$7070) and usual care ($5752; 95% CI, $3814-$7952) groups. Intervention delivery cost an additional $1475 (95% CI, $1230-$1695) per person. The intervention group had a mean daily utility value of 0.78 (95% CI, 0.75-0.80) vs 0.73 (95% CI, 0.71-0.76) for the usual care group. The net mean difference in effectiveness was 0.04 (95% CI, 0.02-0.09) QALY at $883 above usual care. The mean incremental cost effectiveness ratio was $18 239 (95% CI, dominant to $24 408) per QALY gained, with dominant indicating that the intervention resulted in both a net cost savings and a net increase in QALYs. Conclusions and Relevance: Collaborative care for adolescent depression appears to be cost-effective, with 95% CIs far below the strictest willingness-to-pay thresholds. These findings support the use of collaborative care interventions to treat depression among adolescent youth. Trial Registration: clinicaltrials.gov Identifier: NCT01140464. PMID- 27654450 TI - The social, psychological, emotional morbidity and adjustment techniques for women with anal incontinence following Obstetric Anal Sphincter Injury: use of a word picture to identify a hidden syndrome. AB - BACKGROUND: To identify the emotional, social and psychological consequences and recovery process of anal incontinence (AI) following obstetric anal sphincter injuries (OASIS) and explore if this can be identified as a recognisable syndrome with visual representation. METHODS: A qualitative approach was adopted for this study. Data derived from case studies (n = 81) and interviews (n = 14) with women with AI after OASIS was used to identify the emotional, social and psychological consequences of AI after OASIS. Keywords and synonyms were extracted and the power of these statements displayed as a 'word picture'. The validity and authenticity of the word picture was then assessed by: a questionnaire sent to a group of mothers who had experienced this condition (n = 16); a focus group attended by mothers (n = 14) and supported by health professionals (n = 6) and via interviews with health professionals (n = 12) who were involved with helping mothers with AI following OASIS. RESULTS: Women with AI resulting from OASIS have a specific syndrome - the 'OASIS Syndrome' - which we have uniquely visualised as a 'word picture'. They feel unclean which results in dignity loss, psychosexual morbidity, isolation, embarrassment, guilt, fear, grief, feeling low, anxiety, loss of confidence, a feeling of having been mutilated and a compromised role as a mother. Coping relies on repetitive washing (which may become a ritual), planning daily activities around toiletry needs, sharing, family support, employment if possible and attention to the baby. Recovery and healing is through care of the child and hope generated by love within the family. CONCLUSIONS: This study has identified a previously unrecognised 'OASIS Syndrome' and, by way of a new and unique 'word picture', revealed a hidden condition. There should be greater awareness by the public and profession about the 'OASIS Syndrome' and a mechanism for early identification of the condition and referral for management. This, if successful, would overcome the barrier of silence which surrounds this currently unspoken taboo. PMID- 27654452 TI - A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity. AB - BACKGROUND: ( 177)Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during (177)Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2 GBq (3.5-8.3 GBq) of (177)Lu DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168 h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of (177)Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period. RESULTS: The mean absorbed dose to the bone marrow was estimated to 0.20 Gy (0.11-0.37 Gy) per 7.4 GBq of (177)Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p = 0.01), WBC (p < 0.01) and PLT (p < 0.01) counts. The total mean absorbed dose to the bone marrow was 0.64 Gy (0.30-1.5 Gy) per 24 GBq (8.2-37 GBq) of (177)Lu-DOTATATE and also correlated with a decrease in Hb (p < 0.01), WBC (p = 0.01) and PLT (p < 0.01) counts. CONCLUSIONS: The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in (177)Lu-DOTATATE treatment without the need for blood and urine sampling. PMID- 27654451 TI - Diversity of MHC class I alleles in Spheniscus humboldti. AB - The major histocompatibility complex locus (MHC) is a gene region related to immune response and exhibits a remarkably great diversity. We deduced that polymorphisms in MHC genes would help to solve several issues on penguins, including classification, phylogenetic relationship, and conservation. This study aimed to elucidate the structure and diversity of the so far unknown MHC class I gene in a penguin species. The structure of an MHC class I gene from the Humboldt penguin (Spheniscus humboldti) was determined by using an inverse PCR method. We designed PCR primers to directly determine nucleotide sequences of PCR products from the MHC class I gene and to obtain recombinant clones for investigating the diversity of the MHC class I gene in Humboldt penguins. A total of 24 MHC class I allele sequences were obtained from 40 individuals. Polymorphisms were mainly found in exons 2 and 3, as expected from the nature of MHC class I genes in vertebrate species including birds and mammals. Phylogenetic analyses of MHC class I alleles have revealed that the Humboldt penguin is closely related to the Red Knot (Calidris canutus) belonging to Charadriiformes. PMID- 27654453 TI - Is body mass index relevant to prognosis of papillary thyroid carcinoma? A clinicopathological cohort study. AB - PURPOSE: Obesity appears to be related to papillary thyroid carcinoma (PTC) in the observational studies, although its relationship concerning the PTC prognosis has not been established. We investigated the association between body mass index (BMI) and the prognosis of PTC. METHODS: The WHO BMI classification was used to stratify the degree of obesity. The final outcome was disease status, including recurrence and persistence, of 783 PTC patients. We reviewed patients' BMI, disease status, and other prognostic factors retrospectively. RESULTS: The mean BMI was 24.2 kg/m2. When stratified according to the WHO BMI classification, 21 were Underweight, 482 were Normal, 232 were Overweight, and 48 were Obese. We divided patients into two groups: <25.0 kg/m2 (n = 503) vs. >=25.0 kg/m2 (n = 280). The BMI >=25.0 group was older and more likely to be male in a multivariate analysis (p < 0.001). For those with BMI <25.0 and >=25.0, recurrence occurred in 3.0 and 2.1 % (p = 0.486), persistence in 7.2 and 5.1 % (p = 0.265), and either recurrence or persistence in 9.9 and 7.1 %, respectively (p = 0.189). A multivariate analysis revealed that older age and male gender in Overweight vs. Normal, older age in Obese vs. Normal, and advanced T stage in Normal vs. Underweight were statistically significant prognostic factors. CONCLUSIONS: There was no significant difference in the prognosis according to BMI in PTC patients. However, old age, male gender, and advanced T-stage patients were found more frequently in the higher BMI group than in the lower BMI group. PMID- 27654455 TI - Cerebrospinal Fluid Biomarkers in Postconcussion Syndrome: Measuring Neuronal Injury and Distinguishing Individuals at Risk for Persistent Postconcussion Syndrome or Chronic Traumatic Encephalopathy. PMID- 27654454 TI - Comparison of postoperative early and late complications between pancreas-sparing duodenectomy and pancreatoduodenectomy. AB - PURPOSE: Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreatoduodenectomy (PD) for patients with duodenal neoplasms. METHODS: The postoperative early and late complications of 21 patients who underwent PSD between 1992 and 2014 were compared with those of 44 patients with soft pancreatic parenchyma who underwent PD between 2009 and 2014. RESULTS: The median operation time and blood loss were less in the PSD group than in the PD group (P < 0.001). The overall incidence of early complications was less in the PSD group than in the PD group (PSD with ampullectomy vs. PSD without ampullectomy vs. PD; 45.5 vs. 20.0 vs. 56.8 %). The incidence of pancreatic fistula formation and overall incidence of late complications were also less in the PSD group than in the PD group (P = 0.031, 0.020). There were no complications related to the pancreatic endocrine or exocrine functions in the PSD group. CONCLUSION: PSD is a less-invasive procedure and has the advantage over PD of preserving the pancreas. PMID- 27654456 TI - Pineal granuloma masking a germinoma: do not hesitate to repeat the biopsy. PMID- 27654457 TI - Immunotherapy Added to Antibiotic Treatment Reduces Relapse of Disease in a Mouse Model of Tuberculosis. AB - Immune-modulating drugs that target myeloid-derived suppressor cells or stimulate natural killer T cells have been shown to reduce mycobacterial loads in tuberculosis (TB). We aimed to determine if a combination of these drugs as adjunct immunotherapy to conventional antibiotic treatment could also increase therapeutic efficacy against TB. In our model of pulmonary TB in mice, we applied treatment with isoniazid, rifampicin, and pyrazinamide for 13 weeks alone or combined with immunotherapy consisting of all-trans retinoic acid, 1,25(OH)2 vitamin D3, and alpha-galactosylceramide. Outcome parameters were mycobacterial load during treatment (therapeutic activity) and 13 weeks after termination of treatment (therapeutic efficacy). Moreover, cellular changes were analyzed using flow cytometry and cytokine expression was assessed at the mRNA and protein levels. Addition of immunotherapy was associated with lower mycobacterial loads after 5 weeks of treatment and significantly reduced relapse of disease after a shortened 13-week treatment course compared with antibiotic treatment alone. This was accompanied by reduced accumulation of immature myeloid cells in the lungs at the end of treatment and increased TNF-alpha protein levels throughout the treatment period. We demonstrate, in a mouse model of pulmonary TB, that immunotherapy consisting of three clinically approved drugs can improve the therapeutic efficacy of standard antibiotic treatment. PMID- 27654458 TI - Impact of Redox Reactions on Colloid Transport in Saturated Porous Media: An Example of Ferrihydrite Colloids Transport in the Presence of Sulfide. AB - Transport of colloids in the subsurface is an important environmental process with most research interests centered on the transport in chemically stable conditions. While colloids can be formed under dynamic redox conditions, the impact of redox reactions on their transport is largely overlooked. Taking the redox reactions between ferrihydrite colloids and sulfide as an example, we investigated how and to what extent the redox reactions modulated the transport of ferrihydrite colloids in anoxic sand columns over a range of environmentally relevant conditions. Our results reveal that the presence of sulfide (7.8-46.9 MUM) significantly decreased the breakthrough of ferrihydrite colloids in the sand column. The estimated travel distance of ferrihydrite colloids in the absence of sulfide was nearly 7-fold larger than that in the presence of 46.9 MUM sulfide. The reduced breakthrough was primarily attributed to the reductive dissolution of ferrihydrite colloids by sulfide in parallel with formation of elemental sulfur (S(0)) particles from sulfide oxidation. Reductive dissolution decreased the total mass of ferrihydrite colloids, while the negatively charged S(0) decreased the overall zeta potential of ferrihydrite colloids by attaching onto their surfaces and thus enhanced their retention in the sand. Our findings provide novel insights into the critical role of redox reactions on the transport of redox-sensitive colloids in saturated porous media. PMID- 27654460 TI - Open Reduction Internal Fixation of Posterior Malleolus Fractures and Iatrogenic Injuries: A Cadaveric Study. AB - : Open reduction internal fixation of posterior malleolus fractures from a posterior approach is gaining popularity. One concern that has not been studied is the risk of iatrogenic injury to anatomical structures on the anterior ankle. The purpose of this study is to determine the proximity of these anterior structures with relation to K-wires advanced through the anterior cortex. A total of 10 cadaver ankles were utilized in the study. A posterolateral approach to the ankle was used. K-wires were advanced at varying levels above the articular surface, and then, the proximity of the wires to the following structures was determined: the neurovascular bundle, tibialis anterior (TA), and extensor hallucis longus. Overall, the structure most in danger of being injured was the TA (P < .001). This tendon was injured by 52% of all K-wires. These data suggest that K-wires should be advanced under direct fluoroscopic visualization to minimize the risk of iatrogenic injury. LEVELS OF EVIDENCE: Level IV. PMID- 27654459 TI - Prevalence and severity of depressive symptoms in relation to rural-to-urban migration in India: a cross-sectional study. AB - BACKGROUND: Migration is a major life event, which may also be a risk factor for depression. However, little is known regarding the relationship between these phenomena in low and middle income settings. This study explores the frequency and severity of depressive symptoms among rural-to-urban migrants compared to permanent rural and to urban residents in India. METHODS: We assessed 884 subjects; urban non-migrants (n = 159), urban migrants (n = 461) and rural non migrants (n = 264) in Hyderabad, India, in 2009-2010. The frequency and severity of depressive symptoms was assessed with the validated Telugu version of the Brief Patient Health Questionnaire. Multivariable logistic regression was used to examine the association between the presence of depressive symptoms and migration status while adjusting for gender, age and several sociodemographic and health related parameters using Stata v.12. RESULTS: The prevalence of mild to severe depressive symptoms was higher in women (11.3, 95 % confidence interval (CI) 8.3 14.3 %) compared to men (5.8 %, 95 % CI 3.7-7.9 %). Rural residents reported the highest prevalence of mild to severe depressive symptoms (women: 16.7 %, 95 % CI 9.8-23.5 %; men: 8.0 %, 95 % CI 3.7-12.3 %). Among women, the lowest prevalence was reported by migrants (8.2 %, 95 % CI 4.6-11.9 %). Among men, prevalence was similar in migrants (5.0 %, 95 % CI 2.2-7.7 %) and urban residents (3.9 %, 95 % CI 0-8.3 %). Multivariable logistic regression analyses showed no evidence for increased prevalence of mild to severe depressive symptoms among migrants compared to either rural or urban residents. CONCLUSIONS: There was no evidence for an increased prevalence of mild to severe depressive symptoms among rural urban migrants compared to rural or urban residents. PMID- 27654461 TI - Leiomyoma of the Foot and Ankle: A Case Series. AB - : Leiomyoma is a benign soft-tissue tumor that can arise in any soft tissue; however, in the extremities, it is usually a subcutaneous mass. Masses in the foot and ankle in general are rare, and few reports in the literature describe leiomyoma in this region of the body. We present a series of 8 cases of leiomyoma of the foot and ankle, 4 of which are subclassified as angioleiomyomas. The characteristic patient presentation, imaging, and histological findings are presented here to increase awareness of this soft-tissue mass in the foot and ankle. LEVELS OF EVIDENCE: Level V. PMID- 27654462 TI - Size Effect of the Interfacial Mechanical Behavior of Graphene on a Stretchable Substrate. AB - The size effect and deformation transfer of the interface between graphene and a polymer substrate are experimentally investigated. Eight composite specimens, containing polyethylene terephthalate substrate (PET) and eight different sizes of graphene, are designed. The specimens are studied by a series of experiments to explore how the mechanical properties of the tangential interface between graphene and the substrates can be influenced by the size of graphene. Micro Raman spectroscopy is employed to measure the full-field strain of graphene subjected to a uniaxial tensile loading process, based on which the evolution of the bonding states of the interface is obtained. The existence of a size effect in the interfacial strain transfer process at the graphene/PET interface is observed, and this phenomenon is characterized by a size threshold and an innovatively defined parameter called the critical relative transfer length. Combined with previous experimental results on the tangential interface of graphene, we observe that the size effect of the interfacial shear stress of graphene is the main cause for the inconformity of experimental data published in previous reports. PMID- 27654463 TI - An Isolable Bismabenzene: Synthesis, Structure, and Reactivity. AB - A stable bismabenzene was synthesized, isolated, and structurally characterized. The prospective aromaticity of this heavy benzene, bearing a sixth-row element, was examined by X-ray crystallography and NMR and UV-vis spectroscopy, as well as theoretical DFT calculations. Structural analysis of this bismabenzene revealed a planar ring containing unsaturated Bi-C and C-C bonds. As bond alternations could not be observed, these results are consistent with the formal criteria of aromaticity. Theoretical calculations also support the aromatic nature of this bismabenzene, which reacted with an alkyne to form the corresponding [4+2] cycloadduct, thus demonstrating a small yet tangible aromatic stabilization energy. PMID- 27654464 TI - Electrical impedance tomography to determine optimal positive end-expiratory pressure in severe chronic obstructive pulmonary disease. PMID- 27654465 TI - Comparing Homicide-Suicides in the United States and Sweden. AB - Research on homicides followed by suicides has largely relied on very localized samples and relatively short time spans of data. As a result, little is known about the extent to which patterns within cases of homicide-suicides are geographically specific. The current study seeks to help fill this gap by comparing twenty years of homicide-suicide data for Sweden and a large U.S. county. Although some of the underlying patterns in the two countries are similar (e.g., decreasing rates), a number of important differences emerge, particularly with respect to incidence, weapons used, perpetrator age, and relationship of the perpetrator to the victim. PMID- 27654466 TI - Is the daily use of vacuum erection device for a month before penile prosthesis implantation beneficial? a randomized controlled trial. AB - Patient concerns about penile length after penile prosthesis (PP) implantation for erectile dysfunction (ED) have significant impact on patients and their partners. In addition, corporal fibrosis is associated with difficult PP implantation. The preoperative use of vacuum erectile devices (VED) is an uncommon physical treatment for such concerns. Therefore, the current randomized controlled study assessed two outcomes: whether pre-operative VED use for a month before surgery would significantly increase flaccid stretched penile length (SPL) on the day of surgery, and facilitate easier corporal dilatation intraoperatively. Fifty-one patients scheduled for PP implantation for ED were randomized to either intervention group (pre-operative VED use; 10-15 min/day for >=30 days; Group A; n = 25), or control group (no intervention; Group B; n = 26). A research assistant (blinded to the treatment assignments) recorded SPL at baseline (initial consultation) and on day of surgery. The surgeons performing the PP implantation (also blinded to the treatment assignments) provided subjective assessments of the ease of corporal dilatation. Baseline patient characteristics, demographics, and comorbidities were the same in both groups. Baseline measurements (SPL-1) were 10.71 +/- 1.28 and 10.87 +/- 1.26 cm in Group A and Group B, respectively; and the day of surgery measurements (SPL-2) were 11.50 +/- 1.33 and 11.06 +/- 1.34 cm in Group A and Group B, respectively. In terms of outcomes: mean SPL increase in Group A was significantly more by a mean of 0.80 +/- 0.38 cm (p < 0.05) compared to Group B; and surgeons' subjective report of surgical ease indicated smoother corporal dilatation for Group A compared to Group B. VED use (10-15 min/day during the month prior to PP implantation) was associated with significantly increased SPL on day of surgery, and facilitated easier corporal dilatation intraoperatively. Future studies should examine the long-term outcomes of penile prosthesis implantation after pre operative use of vacuum erectile devices. PMID- 27654467 TI - Passive Tumor Targeting of Polymer Therapeutics: In Vivo Imaging of Both the Polymer Carrier and the Enzymatically Cleavable Drug Model. AB - The enzymatic release of a model drug from a polymer carrier inside a tumor using multispectral optical imaging in vivo in nude mice bearing colorectal carcinomas HT-29 and DLD-1 is demonstrated. Much higher release rate in vivo from a linear (30 kDa) (N-2-hydroxypropyl)methacrylamide-based polymer compared with a high molecular weight branched (170 kDa) polymer conjugate is observed, probably due to steric hindrance of the cleavable spacer of the latter polymer to proteolytic enzymes. There is no significant difference in the relative biodistribution of the two polymers, but the branched polymer circulates much longer. Both polymers are labeled with two different fluorophores. Dyomics-676 as a drug model is attached to the polymer via an enzymatically cleavable Gly-Phe-Leu-Gly spacer; Dyomics 782 is bound to the same polymer via a nondegradable amide bond, enabling the tracking of the polymer carrier after i.v. application to mice. PMID- 27654468 TI - Inability of 'Whole Genome Amplification' to Improve Success Rates for the Biomolecular Detection of Tuberculosis in Archaeological Samples. AB - We assessed the ability of whole genome amplification (WGA) to improve the efficiency of downstream polymerase chain reactions (PCRs) directed at ancient DNA (aDNA) of members of the Mycobacterium tuberculosis complex (MTBC). Using extracts from a variety of bones and a tooth from human skeletons with or without lesions indicative of tuberculosis, from multiple time periods, we obtained inconsistent results. We conclude that WGA does not provide any advantage in studies of MTBC aDNA. The sporadic nature of our results are probably due to the fact that WGA is itself a PCR-based procedure which, although designed to deal with fragmented DNA, might be inefficient with the low concentration of templates in an aDNA extract. As such, WGA is subject to similar, if not the same, restrictions as PCR when applied to aDNA. PMID- 27654469 TI - Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience. AB - AIMS: The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS: Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade G2(r) and recorded real-time sensation (0-100% scale) and standardized verbal sensory thresholds using a novel, touch-screen "sensation meter." 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS: Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. >=3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS: This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity-sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way. PMID- 27654470 TI - Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I. AB - Glycosaminoglycans are known to be associated with extracellular amyloid deposits of various amyloidogenic proteins. In this study, we found that the glycosaminoglycan heparin greatly accelerates the elongation step in fibril formation by the N-terminal 1-83 fragment of human apolipoprotein A-I (apoA-I), especially in the amyloidogenic W50R variant. Using fragment peptides, we demonstrate that heparin significantly promotes beta-transition and fibril formation of the highly amyloidogenic region spanning residues 44-65 and colocalizes with fibrils formed by the W50R variant. These results suggest the possible role of glycosaminoglycans in fibril formation by amyloidogenic apoA-I variants. PMID- 27654471 TI - [2016 European Guidelines on cardiovascular disease prevention in clinical practice]. PMID- 27654472 TI - Massive On-X mitral mechanical prosthetic valve thrombosis in NYHA class I patient. PMID- 27654473 TI - From heart to lung cancer. PMID- 27654474 TI - Severe acute cardiotoxicity following two intravenous doses of cyclophosphamide in an adolescent treated for rapidly progressive glomerulonephritis. PMID- 27654475 TI - First implantation of a HeartMate 3 left ventricular assist device in Poland. PMID- 27654476 TI - [Liposomal doxorubicin in patients with breast cancer and concomitant cardiovascular diseases - interdisciplinary expert opinion]. AB - The use of liposomal doxorubicin in place of conventional form can significantly reduce the risk of clinically important cardiovascular complications of chemotherapy. The use of liposomal doxorubicin-containing regimen seems to be the most justified in treatment of breast cancer patients with coexisting cardiovascular diseases. The document defines the possible clinical scenarios for the use of chemotherapy with liposomal doxorubicin and presents the optimal cardiac monitoring of this therapy. PMID- 27654477 TI - Water mass mixing shapes bacterial biogeography in a highly hydrodynamic region of the Southern Ocean. AB - Even though compelling evidences indicate that marine microbes show biogeographic patterns, very little is known on the mechanisms driving those patterns in aquatic ecosystems. In the present study, bacterial community structure was examined in epipelagic waters of a highly hydrodynamic area of the Southern Ocean to gain insight into the role that biogeochemical factors and water mass mixing (a proxy of dispersal) have on microbial biogeography. Four water masses that converge and mix around the South Shetland Islands (northern tip of the Antarctic Peninsula) were investigated. Bacterioplankton communities were water-mass specific, and were best explained by dispersal rather than by biogeochemical factors, which is attributed to the relatively reduced environmental gradients found in these cold and nutrient rich waters. These results support the notion that currents and water mixing may have a considerable effect in connecting and transforming different water bodies, and consequently, in shaping communities of microorganisms. Considering the multidimensional and dynamic nature of the ocean, analysis of water mass mixing is a more suitable approach to investigate the role of dispersal on the biogeography of planktonic microorganisms rather than geographical distance. PMID- 27654479 TI - A Faster, Unbiased Path Opening by Upper Skeletonization and Weighted Adjacency Graphs. AB - The path opening is a filter that preserves bright regions in the image in which a path of a certain length L fits. A path is a (not necessarily straight) line defined by a specific adjacency relation. The most efficient implementation known scales as O(min(L, d, Q) N) with the length of the path, L , the maximum possible path length, d , the number of graylevels, Q , and the image size, N . An approximation exists (parsimonious path opening) that has an execution time independent of path length. This is achieved by preselecting paths, and applying 1D openings along these paths. However, the preselected paths can miss important structures, as described by its authors. Here, we propose a different approximation, in which we preselect paths using a grayvalue skeleton. The skeleton follows all ridges in the image, meaning that no important line structures will be missed. An H-minima transform simplifies the image to reduce the number of branches in the skeleton. A graph-based version of the traditional path opening operates only on the pixels in the skeleton, yielding speedups up to one order of magnitude, depending on image size and filter parameters. The edges of the graph are weighted in order to minimize bias. Experiments show that the proposed algorithm scales linearly with image size, and that it is often slightly faster for longer paths than for shorter paths. The algorithm also yields the most accurate results-as compared with a number of path opening variants-when measuring length distributions. PMID- 27654480 TI - Pedestrian Detection Inspired by Appearance Constancy and Shape Symmetry. AB - Most state-of-the-art methods in pedestrian detection are unable to achieve a good trade-off between accuracy and efficiency. For example, ACF has a fast speed but a relatively low detection rate, while checkerboards have a high detection rate but a slow speed. Inspired by some simple inherent attributes of pedestrians (i.e., appearance constancy and shape symmetry), we propose two new types of non neighboring features: side-inner difference features (SIDF) and symmetrical similarity features (SSFs). SIDF can characterize the difference between the background and pedestrian and the difference between the pedestrian contour and its inner part. SSF can capture the symmetrical similarity of pedestrian shape. However, it is difficult for neighboring features to have such above characterization abilities. Finally, we propose to combine both non-neighboring features and neighboring features for pedestrian detection. It is found that non neighboring features can further decrease the log-average miss rate by 4.44%. The relationship between our proposed method and some state-of-the-art methods is also given. Experimental results on INRIA, Caltech, and KITTI data sets demonstrate the effectiveness and efficiency of the proposed method. Compared with the state-of-the-art methods without using CNN, our method achieves the best detection performance on Caltech, outperforming the second best method (i.e., checkerboards) by 2.27%. Using the new annotations of Caltech, it can achieve 11.87% miss rate, which outperforms other methods. PMID- 27654482 TI - Multi-View 3D Object Retrieval With Deep Embedding Network. AB - In multi-view 3D object retrieval, each object is characterized by a group of 2D images captured from different views. Rather than using hand-crafted features, in this paper, we take advantage of the strong discriminative power of convolutional neural network to learn an effective 3D object representation tailored for this retrieval task. Specifically, we propose a deep embedding network jointly supervised by classification loss and triplet loss to map the high-dimensional image space into a low-dimensional feature space, where the Euclidean distance of features directly corresponds to the semantic similarity of images. By effectively reducing the intra-class variations while increasing the inter-class ones of the input images, the network guarantees that similar images are closer than dissimilar ones in the learned feature space. Besides, we investigate the effectiveness of deep features extracted from different layers of the embedding network extensively and find that an efficient 3D object representation should be a tradeoff between global semantic information and discriminative local characteristics. Then, with the set of deep features extracted from different views, we can generate a comprehensive description for each 3D object and formulate the multi-view 3D object retrieval as a set-to-set matching problem. Extensive experiments on SHREC'15 data set demonstrate the superiority of our proposed method over the previous state-of-the-art approaches with over 12% performance improvement. PMID- 27654481 TI - Hierarchical Representation Learning for Kinship Verification. AB - Kinship verification has a number of applications such as organizing large collections of images and recognizing resemblances among humans. In this paper, first, a human study is conducted to understand the capabilities of human mind and to identify the discriminatory areas of a face that facilitate kinship-cues. The visual stimuli presented to the participants determine their ability to recognize kin relationship using the whole face as well as specific facial regions. The effect of participant gender and age and kin-relation pair of the stimulus is analyzed using quantitative measures such as accuracy, discriminability index d' , and perceptual information entropy. Utilizing the information obtained from the human study, a hierarchical kinship verification via representation learning (KVRL) framework is utilized to learn the representation of different face regions in an unsupervised manner. We propose a novel approach for feature representation termed as filtered contractive deep belief networks (fcDBN). The proposed feature representation encodes relational information present in images using filters and contractive regularization penalty. A compact representation of facial images of kin is extracted as an output from the learned model and a multi-layer neural network is utilized to verify the kin accurately. A new WVU kinship database is created, which consists of multiple images per subject to facilitate kinship verification. The results show that the proposed deep learning framework (KVRL-fcDBN) yields the state-of the-art kinship verification accuracy on the WVU kinship database and on four existing benchmark data sets. Furthermore, kinship information is used as a soft biometric modality to boost the performance of face verification via product of likelihood ratio and support vector machine based approaches. Using the proposed KVRL-fcDBN framework, an improvement of over 20% is observed in the performance of face verification. PMID- 27654478 TI - Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial mesenchymal transition of gastric cancer. AB - LncRNAs play critical roles in gastric cancer (GC). In this study, the expression of fourteen cancer related lncRNAs were investigated in paired tissues of 66 patients with GC, real-time RT-PCR revealed that ZFAS1 was significantly upregulated. We then examined the expression of ZFAS1 in plasmas derived from 77 GC patients before- and post-operations and 60 healthy individuals, and found that circulating ZFAS1 was also upregulated in GC patients and operation can reduce its presence in plasma. To investigate the potential mechanisms, we compared the expression of ZFAS1 in multiple gastric cell lines and one normal cell line and found that ZFAS1 was up-regulated in GC cell lines. Furthermore, circulating tumor cells (CTC) were simulated by mixing GC cells with peripheral blood. After EpCAM antibody-based cell sorting, we found that the expression of ZFAS1 was positively correlated with EMT property of CTCs. In GC patient tissue samples, we found that Twist was positively correlated with ZFAS1 by immunohistochemical staining. Taken together, our results suggested that ZFAS1 was up-regulated in both tissues and plasmas of GC patients, and may be involved in regulation of EMT in GC progression. Thus, ZFAS1 might serve as a potential diagnostic marker and/or therapeutic target for GC. PMID- 27654483 TI - Structure Integral Transform Versus Radon Transform: A 2D Mathematical Tool for Invariant Shape Recognition. AB - In this paper, we present a novel mathematical tool, Structure Integral Transform (SIT), for invariant shape description and recognition. Different from the Radon Transform (RT), which integrates the shape image function over a 1D line in the image plane, the proposed SIT builds upon two orthogonal integrals over a 2D K cross dissecting structure spanning across all rotation angles by which the shape regions are bisected in each integral. The proposed SIT brings the following advantages over the RT: 1) it has the extra function of describing the interior structural relationship within the shape which provides a more powerful discriminative ability for shape recognition; 2) the shape regions are dissected by the K -cross in a coarse to fine hierarchical order that can characterize the shape in a better spatial organization scanning from the center to the periphery; and 3) it is easier to build a completely invariant shape descriptor. The experimental results of applying SIT to shape recognition demonstrate its superior performance over the well-known Radon transform, and the well-known shape contexts and the polar harmonic transforms. PMID- 27654485 TI - Unsupervised Domain Adaptation With Label and Structural Consistency. AB - Unsupervised domain adaptation deals with scenarios in which labeled data are available in the source domain, but only unlabeled data can be observed in the target domain. Since the classifiers trained by source-domain data would not be expected to generalize well in the target domain, how to transfer the label information from source to target-domain data is a challenging task. A common technique for unsupervised domain adaptation is to match cross-domain data distributions, so that the domain and distribution differences can be suppressed. In this paper, we propose to utilize the label information inferred from the source domain, while the structural information of the unlabeled target-domain data will be jointly exploited for adaptation purposes. Our proposed model not only reduces the distribution mismatch between domains, improved recognition of target-domain data can be achieved simultaneously. In the experiments, we will show that our approach performs favorably against the state-of-the-art unsupervised domain adaptation methods on benchmark data sets. We will also provide convergence, sensitivity, and robustness analysis, which support the use of our model for cross-domain classification. PMID- 27654484 TI - Dynamic Parallel and Distributed Graph Cuts. AB - Graph cuts are widely used in computer vision. To speed up the optimization process and improve the scalability for large graphs, Strandmark and Kahl introduced a splitting method to split a graph into multiple subgraphs for parallel computation in both shared and distributed memory models. However, this parallel algorithm (the parallel BK-algorithm) does not have a polynomial bound on the number of iterations and is found to be non-convergent in some cases due to the possible multiple optimal solutions of its sub-problems. To remedy this non-convergence problem, in this paper, we first introduce a merging method capable of merging any number of those adjacent sub-graphs that can hardly reach agreement on their overlapping regions in the parallel BK-algorithm. Based on the pseudo-boolean representations of graph cuts, our merging method is shown to be effectively reused all the computed flows in these sub-graphs. Through both splitting and merging, we further propose a dynamic parallel and distributed graph cuts algorithm with guaranteed convergence to the globally optimal solutions within a predefined number of iterations. In essence, this paper provides a general framework to allow more sophisticated splitting and merging strategies to be employed to further boost performance. Our dynamic parallel algorithm is validated with extensive experimental results. PMID- 27654486 TI - Self-Organized Stationary Patterns in Networks of Bistable Chemical Reactions. AB - Experiments with networks of discrete reactive bistable electrochemical elements organized in regular and nonregular tree networks are presented to confirm an alternative to the Turing mechanism for the formation of self-organized stationary patterns. The results show that the pattern formation can be described by the identification of domains that can be activated individually or in combinations. The method also enabled the localization of chemical reactions to network substructures and the identification of critical sites whose activation results in complete activation of the system. Although the experiments were performed with a specific nickel electrodissolution system, they reproduced all the salient dynamic behavior of a general network model with a single nonlinearity parameter. Thus, the considered pattern-formation mechanism is very robust, and similar behavior can be expected in other natural or engineered networked systems that exhibit, at least locally, a treelike structure. PMID- 27654487 TI - Right Ventricular Dysfunction Complicates Time in Therapeutic Range in Heart Failure Patients Receiving Warfarin. AB - AIM: We aimed to evaluate the effect of echocardiographically demonstrated right ventricular dysfunction (RVD) on time in therapeutic range (TTR) in heart failure (HF) patients receiving warfarin therapy. METHODS: A total of 893 consecutive HF patients were included and classified into 4 different subgroups: HF with preserved ejection fraction (HFpEF) without RVD (n = 373), HF with reduced EF (HFrEF) without RVD (n = 215), HFpEF with RVD (n = 106) and HFrEF with RVD (n = 199). Groups were compared according to baseline, demographic and clinical data and the characteristics of warfarin therapy. RESULTS: Presence of RVD yielded lower median TTR values both in HFpEF and HFrEF patients. RVD, current smoking, New York Heart Association functional class III/IV, hypertension, diabetes mellitus, pulmonary disease, prior transient ischemic attack or stroke, chronic kidney disease (CKD) stage 4/5 and CKD stage 3 were found to be independent predictors of poor anticoagulation control in multivariate logistic regression analysis. CONCLUSIONS: The present study demonstrated that presence of RVD in HF increases the risk for poor anticoagulation. PMID- 27654488 TI - Assessing non-metro recovery across two continents: issues and limitations. AB - Rural and remote areas of countries such as Australia and the United States are less well-resourced and often poorer than their city counterparts. When a disaster strikes, therefore, their long-term recovery can be impeded by being situated 'over the horizon'. Nonetheless, they are likely to enjoy higher social capital, with 'locals' banding together to help restore economic and social life in the wake of a calamitous incident. At the same time, a repeat of extreme events, springing in part from alteration to the landscape through intense human occupation, threatens to derail sustainable recovery processes everywhere, suggesting that renewed emphasis needs to be placed on preparedness. Improved metrics are also required, spanning both pre- and post-disaster phases, to determine effectiveness. Moreover, a focus on the 'hardening' of towns offers a better return in limiting damage and potentially hastens the speed of recovery should these places later fall victim to extreme events. PMID- 27654489 TI - Deairing Techniques for Double-Ended Centrifugal Total Artificial Heart Implantation. AB - The unique device architecture of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) requires dedicated and specific air-removal techniques during device implantation in vivo. These procedures comprise special surgical techniques and intraoperative manipulations, as well as engineering design changes and optimizations to the device itself. The current study evaluated the optimal air-removal techniques during the Cleveland Clinic double-ended centrifugal CFTAH in vivo implants (n = 17). Techniques and pump design iterations consisted of developing a priming method for the device and the use of built-in deairing ports in the early cases (n = 5). In the remaining cases (n = 12), deairing ports were not used. Dedicated air-removal ports were not considered an essential design requirement, and such ports may represent an additional risk for pump thrombosis. Careful passive deairing was found to be an effective measure with a centrifugal pump of this design. In this report, the techniques and design changes that were made during this CFTAH development program to enable effective residual air removal and prevention of air embolism during in vivo device implantation are explained. PMID- 27654490 TI - A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials. AB - BACKGROUND: Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic agents have reported objective response rates (ORRs) and toxic death rates of 7.9-9.6% and 0.5%, respectively. These data may not reflect safety and efficacy in phase I trials of molecularly targeted (targeted) drugs. METHODS: A systematic review of pediatric phase I solid tumor trials published in 1990-2013 was performed. The published reports were evaluated for patient characteristics, toxicity information, and response numbers. RESULTS: A total of 143 phase I pediatric clinical trials enrolling 3,896 children involving 53 targeted and 48 cytotoxic drugs were identified. A meta-analysis demonstrated that the ORR is 2.1-fold higher with cytotoxic drugs (0.066 vs. 0.031 per subject; P = 0.007). By contrast, the pooled estimate of the stable disease rate (SDR) is similar for cytotoxic and targeted drugs (0.2 vs. 0.23 per subject; P = 0.27). The pooled estimate of the dose-limiting toxicity rate is 1.8-fold larger with cytotoxic drugs (0.24 vs. 0.13 per subject; P = 0.0003). The hematologic grade 3-4 (G3/4) toxicity rate is 3.6-fold larger with cytotoxic drugs (0.43 vs. 0.12 per treatment course; P = 0.0001); however, the nonhematologic G3/4 toxicities and toxic deaths occur at similar rates for cytotoxic and targeted drugs. CONCLUSIONS: In phase I pediatric solid tumor trials, ORRs were significantly higher for cytotoxic versus targeted agents. SDRs were similar in targeted and cytotoxic drug trials. Patients treated with cytotoxic agents were more likely to experience hematologic G3/4 toxicities than those patients receiving targeted drugs. PMID- 27654491 TI - From Macromolecular to Small-Molecular Triggers: Facile Method toward Photoinduced LCST Phase Behavior of Thermoresponsive Polymers in Mixed Ionic Liquids Containing an Azobenzene Moiety. AB - Instead of the reported photoinduced lower critical solution temperature (LCST) phase transition behavior in ionic liquids (ILs) achieved by photofunctional polymers, this study reports the facile photoinduced LCST phase behavior of nonfunctionalized polymers (poly(benzyl methacrylate) (PBnMA) and poly(2 phenylethyl methacrylate) (PPhEtMA)) in mixed ILs (1,3-dimethylimidazolium bis(trifluoromethanesulfonyl)amide; [C1 mim][NTf2 ] and a newly designed functionalized IL containing an azobenzene moiety (1-butyl-3-(4 phenylazobenzyl)imidazolium bis(trifluoromethanesulfonyl)amide; [Azo][NTf2 ])) as a small-molecular photo trigger. Interestingly, the length of the alkyl spacer between the ester and aryl groups, which is the only structural difference between the two polymers, leads to two different photoresponsive LCST phase transition behaviors. On the basis of spectroscopic studies, the different phase transition behaviors of PBnMA and PPhEtMA may attribute to the different cooperative interactions between the polymers and [C1 mim][NTf2 ]. PMID- 27654492 TI - Walking in hospital is associated with a shorter length of stay in older medical inpatients. AB - Evidence suggests that inactivity during a hospital stay is associated with poor health outcomes in older medical inpatients. We aimed to estimate the associations of average daily step-count (walking) in hospital with physical performance and length of stay in this population. Medical in-patients aged ?65 years, premorbidly mobile, with an anticipated length of stay ?3 d, were recruited. Measurements included average daily step-count, continuously recorded until discharge, or for a maximum of 7 d (Stepwatch Activity Monitor); co morbidity (CIRS-G); frailty (SHARE F-I); and baseline and end-of-study physical performance (short physical performance battery). Linear regression models were used to estimate associations between step-count and end-of-study physical performance or length of stay. Length of stay was log transformed in the first model, and step-count was log transformed in both models. Similar models were used to adjust for potential confounders. Data from 154 patients (mean 77 years, SD 7.4) were analysed. The unadjusted models estimated for each unit increase in the natural log of step-count, the natural log of length of stay decreased by 0.18 (95% CI -0.27 to -0.09). After adjustment of potential confounders, while the strength of the inverse association was attenuated, it remained significant (beta log(steps) = -0.15, 95%CI -0.26 to -0.03). The back-transformed result suggested that a 50% increase in step-count was associated with a 6% shorter length of stay. There was no apparent association between step-count and end-of study physical performance once baseline physical performance was adjusted for. The results indicate that step-count is independently associated with hospital length of stay, and merits further investigation. PMID- 27654493 TI - Placental transfusion: a review. AB - Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID- 27654495 TI - A free parking trial to increase visitation and improve extremely low birth weight infant outcomes. AB - OBJECTIVE: Frequent parental visits are likely to benefit infants in a neonatal intensive care unit (NICU), particularly extremely low birth weight (ELBW; ?1000 g) survivors. Parking costs (?$10 per visit in our center) may deter visitation, especially for low-income parents. We assessed whether free parking (FP) decreased survivors' length of stay (LOS). STUDY DESIGN: Parents (N=138) of ELBW infants (7 to 14 days old) were randomized to usual care (UC; n=66) or FP (n=72). The primary outcome was LOS. RESULTS: Among survivors (n=116), LOS was not significantly less with FP than UC (means: FP=89, UC=102 days, P=0.22; medians: FP=82, UC=84 days, P=0.30). Groups did not differ significantly on proportion of visit days (FP=0.69, UC=0.72, P=0.47), parental involvement, knowledge/skills and satisfaction. Post hoc analyses found that parents with a greater income, a car and fewer children visited more. CONCLUSION: More potent interventions than FP are needed to increase parental visits and reduce LOS for ELBW infants in disadvantaged urban populations. PMID- 27654496 TI - CBT for Child PTSD is Associated with Reductions in Maternal Depression: Evidence for Bidirectional Effects. AB - Cognitive behavioral therapy techniques are empirically supported for posttraumatic stress disorder (PTSD) in youth, but the role of parents in such treatments is less clear. Theoretically there may be a reciprocal relationship such that as children improve, their parents may feel better, and conversely as parents feel better, psychologically the child may improve or improve at a greater rate. This study tested if there were indirect effects of change in child PTSD symptoms on change in parent depression symptoms, and vice versa, across treatment sessions. The data came from a randomized trial of treatment for PTSD and included youth (N = 47) 7-18 years old (51.1% female; ethnicity was reported as 40.4% White and 40.4% Black, with the remainder reporting Mixed [17%] or other ethnicity [2.1%]) who had been exposed to trauma and experienced significant PTSD symptoms. Maternal depression and child PTSD symptoms were assessed at each session. Maternal perceptions of who changed first were also assessed at posttreatment. Maternal depression significantly decreased over the course of treatment, and maternal depression had an indirect effect on child PTSD symptom change. Evidence for the reciprocal relationship, child symptom change having an indirect effect on parent symptom change, was also found. Age, gender, and treatment condition did not moderate these indirect effects. Findings highlight the potential benefits of child therapy on parents and the reciprocal benefits of improved parent symptoms on the child. PMID- 27654494 TI - The role of post-mortem MRI in the neonatal intensive care unit. AB - OBJECTIVE: Post-mortem examination can provide important information about the cause of death and play a significant role in the bereavement process. Autopsies reveal previous unknown medical problems approximately 20 to 30% of the time. A non-invasive magnetic resonance imaging-based post-mortem examination (PM-MRI) may provide an alternative for families who do not consent to an autopsy. STUDY DESIGN: This study was a prospective observational study of recently expired neonates and infants. Subjects underwent a full body MRI scan (brain, chest, abdomen and pelvis) followed by conventional autopsy if the family desired to have one. MRI results were compared with autopsy findings and the ante-mortem clinical diagnosis. A follow-up survey was conducted to investigate family perceptions of the PM-MRI process. RESULTS: Thirty-one infants underwent full PM MRI. Of 31 infants, 19 (61%) had complete agreement between the clinician's impression and PM-MRI. Twenty-four infants also had conventional autopsy, with 14/24 (58%) infants having PM-MRI results consistent with autopsy findings. PM MRI was superior at detection of free intraperitoneal/intrathoracic air and hepatic iron overload. Whole-body PM-MRI did not have the resolution to detect focal/microscopic injury, vascular remodeling and some forms of brain injury. Of those families who remembered the PM-MRI findings, the majority felt that the information was useful. CONCLUSIONS: PM-MRI studies may provide an important adjunct to conventional autopsy and a substitute when the latter is not possible for personal or religious reasons. Clinicians should be aware of, and communicate with the family, the resolution limits of the whole-body PM-MRI to detect certain types of injury. PMID- 27654497 TI - The World Health Organization Recommendations for Trachoma Surveillance, Experience in Nepal and Added Benefit of Testing for Antibodies to Chlamydia trachomatis pgp3 Protein: NESTS Study. AB - BACKGROUND: The World Health Organization (WHO) now requires a second surveillance survey for trachoma after an impact assessment has found follicular trachoma (TF) <5% to determine if re-emergence has occurred. Using new WHO guidelines, we undertook surveillance surveys, and determined the prevalence of infection and antibody positivity, in two districts in Nepal. METHODS: 20 clusters were randomly selected within each district, 15 were randomly selected for antibody testing. In each cluster, we randomly selected 50 children ages 1-9 years and 100 adults >=15 years. TF and trachomatous trichiasis (TT) were evaluated. Conjunctival swabs to test for chlamydial infection using GenXpert platform were obtained, and dried blood spots were collected to test for antibodies to Chlamydia Trachomatis pgp3 using the Luminex platform. FINDINGS: 3 cases of TF were found in the two districts, and one case of infection. Pgp3 antibody positivity was 2.4% (95% confidence interval: 1.4%, 3.7%), and did not increase with age (P = 0.24). No clustering of antibody positivity within communities was found. TT prevalence was <1/1,000 population. INTERPRETATION: The surveillance surveys, as proposed by WHO, showed no evidence for re-emergence of trachoma in two districts of Nepal. The low level and no significant increase by age in seroprevalence of antibodies to C trachomatis pgp3 antigen deserve further investigation as a marker of interruption of transmission. PMID- 27654499 TI - Anti-inflammatory trends of new benzimidazole derivatives. AB - AIM: In present study, the anti-inflammatory activities of a new series of benzimidazole derivatives were studied, investigating their inhibition of secretory phospholipase A2, lipoxygenase, COXs and lipopolysaccharide-induced secretion of TNF-alpha and IL-6 in mouse RAW264.7 macrophages. RESULTS: Synthesized compounds effectively inhibited proinflammatory enzymes and cytokines. CONCLUSION: A strong inhibition of secretory phospholipases A2 was exhibited by benzimidazole derivatives with trifluoromethyl and methoxy substitutions at position 4 of attached phenyl, whereas compound 8 containing pyridine ring substituted with amino group showed very potent 5-lipoxygenase inhibition. Molecular docking experiments were carried out to elucidate the molecular basis of the observed inhibitory activities. PMID- 27654500 TI - [History of anesthesia : "From narcosis to perioperative homeostasis"]. AB - In the western World 16 October 1846 is often called "Ether Day", marking the beginning of anesthesia. Before that date, for physicians there was only a struggle against pain. In the following 170 years all fields of general anesthesia as well as regional and local anesthesia were continuously developed. Pharmacological developments and technical innovations made this evolution possible. The complexity of this field of medicine requires a specialist: the anesthesiologist, whose selection of the most suitable form of anesthesia for the patient makes the surgical intervention painless. In addition, the history of anesthesia was characterized by personalities who were responsible for the progress of this medical field. Anesthesia is one part of the discipline of anesthesiology, which also includes resuscitation, intensive care medicine, emergency medicine and pain therapy. PMID- 27654498 TI - Participation of Children in Medical Decision-Making: Challenges and Potential Solutions. AB - Participation in healthcare decision-making is considered to be an important right of minors, and is highlighted in both international legislation and public policies. However, despite the legal recognition of children's rights to participation, and also the benefits that children experience by their involvement, there is evidence that legislation is not always translated into healthcare practice. There are a number of factors that may impact on the ability of the child to be involved in decisions regarding their medical care. Some of these factors relate to the child, including their capacity to be actively involved in these decisions. Others relate to the family situation, sociocultural context, or the underlying beliefs and practices of the healthcare provider involved. In spite of these challenges to including children in decisions regarding their clinical care, we argue that it is an important factor in their treatment. The extent to which children should participate in this process should be determined on a case-by-case basis, taking all of the potential barriers into account. PMID- 27654501 TI - Renal infarction due to ergotamine. PMID- 27654502 TI - Age and the economics of an emergency medical admission-what factors determine costs? AB - Background: The ageing of the population may be anticipated to increase demand on hospital resources. We have investigated the relationship between hospital episode costs and age profile in a single centre. Methods: All Emergency Medical admissions (33 732 episodes) to an Irish hospital over a 6-year period, categorized into three age groups, were evaluated against total hospital episode costs. Univariate and adjusted incidence rate ratios (IRRs) were calculated using zero truncated Poisson regression. Results: The total hospital episode cost increased with age ( P < 0.001). The multi-variable Poisson regression model demonstrated that the most important drivers of overall costs were Acute Illness Severity-IRR 1.36 (95% CI: 1.30, 1.41), Sepsis Status -1.46 (95% CI: 1.42, 1.51) and Chronic Disabling Disease Score -1.25 (95% CI: 1.22, 1.27) and the Age Group as exemplified for those 85 years IRR 1.23 (95% CI: 1.15, 1.32). Conclusion: Total hospital episode costs are a product of clinical complexity with contributions from the Acute Illness Severity, Co-Morbidity, Chronic Disabling Disease Score and Sepsis Status. However age is also an important contributor and an increasing patient age profile will have a predictable impact on total hospital episode costs. PMID- 27654503 TI - Orbital emphysema after nose blowing. PMID- 27654504 TI - Tension pneumoventricle and cerebrospinal fluid rhinorrhea. PMID- 27654505 TI - Risk for Congenital Malformation With H1N1 Influenza Vaccine: A Cohort Study With Sibling Analysis. AB - Background: Earlier studies reporting varying risk estimates for congenital malformation in offspring of mothers undergoing vaccination against H1N1 influenza during pregnancy did not consider the potential role of confounding by familial (genetic and shared environmental) factors. Objective: To evaluate an association between maternal H1N1 vaccination during pregnancy and offspring malformation, with familial factors taken into account. Design: Population-based prospective study. Setting: Sweden. Participants: Liveborn offspring born between 1 October 2009 and 1 October 2011 to mothers receiving monovalent AS03-adjuvanted H1N1 influenza vaccine (Pandemrix [GlaxoSmithKline]) during pregnancy. A total of 40 983 offspring were prenatally exposed to the vaccine, 14 385 were exposed within the first trimester (14 weeks), and 7502 were exposed during the first 8 weeks of pregnancy. Exposed offspring were compared with 197 588 unexposed offspring. Corresponding risks in exposed versus unexposed siblings were also estimated. Measurements: Congenital malformation, with subanalyses for congenital heart disease, oral cleft, and limb deficiency. Results: Congenital malformation was observed in 2037 (4.97%) exposed offspring and 9443 (4.78%) unexposed offspring. Adjusted risk for congenital malformation was 4.98% in exposed offspring versus 4.96% in unexposed offspring (risk difference, 0.02% [95% CI, 0.26% to 0.30%]). The corresponding risk differences were 0.16% (CI, -0.23% to 0.56%) for vaccination during the first trimester and 0.10% (CI, -0.41% to 0.62%) for vaccination in the first 8 weeks. Using siblings as comparators yielded no statistically significant risk differences. Limitations: The study was based on live births, and the possibility that data on miscarriage or induced abortion could have influenced the findings cannot be ruled out. Study power was limited in analyses of specific malformations. Conclusion: When intrafamilial factors were taken into consideration, H1N1 vaccination during pregnancy did not seem to be linked to overall congenital malformation in offspring, although risk increases for specific malformations could not be ruled out completely. Primary Funding Source: Swedish Research Council and Swedish Council for Working Life and Social Research. PMID- 27654506 TI - No haste, more taste: An EMA study of the effects of stress, negative and positive emotions on eating behavior. AB - OBJECTIVES: Stress and emotions alter eating behavior in several ways: While experiencing negative or positive emotions typically leads to increased food intake, stress may result in either over- or undereating. Several participant characteristics, like gender, BMI and restrained, emotional, or external eating styles seem to influence these relationships. Thus far, most research relied on experimental laboratory studies, thereby reducing the complexity of real-life eating episodes. The aim of the present study was to delineate the effects of stress, negative and positive emotions on two key facets of eating behavior, namely taste- and hunger-based eating, in daily life using ecological momentary assessment (EMA). Furthermore, the already mentioned individual differences as well as time pressure during eating, an important but unstudied construct in EMA studies, were examined. METHODS: Fifty-nine participants completed 10days of signal-contingent sampling and data were analyzed using multilevel modeling. RESULTS: Results revealed that higher stress led to decreased taste-eating which is in line with physiological stress-models. Time pressure during eating resulted in less taste- and more hunger-eating. In line with previous research, stronger positive emotions went along with increased taste-eating. Emotional eating style moderated the relationship between negative emotions and taste-eating as well as hunger-eating. BMI moderated the relationship between negative as well as positive emotions and hunger-eating. CONCLUSIONS: These findings emphasize the importance of individual differences for understanding eating behavior in daily life. Experienced time pressure may be an important aspect for future EMA eating studies. PMID- 27654508 TI - Being Young and Getting Cancer: Development of a Questionnaire Reflecting the Needs and Experiences of Adolescents and Young Adults with Cancer. AB - PURPOSE: Cancer is the leading cause of nonaccidental deaths among adolescents and young adults (AYAs). In Denmark, there are substantial gaps in knowledge concerning how AYAs with cancer perceive their diagnostic and therapeutic trajectory and report health-related outcomes. The aim of this study is to describe the development of a questionnaire targeting AYAs with cancer aiming to evaluate treatment and survivorship from the perspective of the patients. METHODS: Identification of themes and development of items included in the questionnaire were based on a synthesis of literature and qualitative interviews with AYAs in an iterative process involving both a professional advisory panel and a youth panel. During the development process, items were validated through cognitive interviews. RESULTS: The final questionnaire contained 151 closed- and open-ended items divided into 6 sections regarding: (1) "Time before treatment," (2) "Being told about your illness," (3) "Being a young patient," (4) "Your treatment," (5) "Receiving help living with and after Cancer," and (6) "How are you feeling today?." One hundred one items were specifically developed for this study, while 50 were standardized validated indexes. The questionnaire combined different types of items such as needs, preferences, experiences, and patient reported outcomes. CONCLUSION: This is one of few developed questionnaires aiming to evaluate the perspective of AYAs with cancer through their whole cancer trajectory. Results from the questionnaire survey are intended for quality improvements and research in AYA cancer care. The study highlights the importance of an extensive patient involvement in all steps of a questionnaire development process. PMID- 27654507 TI - The Primary Effect on the Proteome of ARID1A-mutated Ovarian Clear Cell Carcinoma is Downregulation of the Mevalonate Pathway at the Post-transcriptional Level. AB - Inactivating mutations in ARID1A, which encodes a subunit of the SWI/SNF chromatin-remodeling complex, are found in over half of ovarian clear cell carcinoma cases and more broadly across most types of cancers. To identify ARID1A dependent changes in intracellular signaling pathways, we performed proteome analyses of isogenic ovarian clear cell carcinoma cell lines with or without ARID1A expression. Knockout of ARID1A in an ovarian clear cell carcinoma cell line with wild-type ARID1A, OVCA429, primarily resulted in downregulation of the mevalonate pathway, an important metabolic pathway involved in isoprenoid synthesis, cholesterol synthesis, and other downstream pathways. In a complementary experiment, expression of wild-type ARID1A in an ovarian clear cell carcinoma cell line containing mutated ARID1A, OVISE, affected the mevalonate pathway in a reciprocal manner. A striking aspect of these analyses was that, although only 5% of the detected proteome showed significant abundance changes, most proteins in the mevalonate pathway were coordinately affected by ARID1A status. There were generally corresponding changes when comparing the proteomics data to our previously published microarray data for ectopic expression of ARID1A in the OVISE cell line. However, ARID1A-dependent changes were not detected for genes within the mevalonate pathway. This discrepancy suggests that the mevalonate pathway is not regulated directly by ARID1A-mediated transcription and may be regulated post-transcriptionally. We conclude that ARID1A status indirectly influences the mevalonate pathway and probably influences other processes including glycogen metabolism and 14-3-3-mediated signaling. Further, our findings demonstrate that changes in mRNA levels are sometimes poor indicators of signaling pathways affected by gene manipulations in cancer cells. PMID- 27654509 TI - Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Reunion Island, 2011-2012. AB - In Reunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner's network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Reunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI. PMID- 27654510 TI - UbC-StarTrack, a clonal method to target the entire progeny of individual progenitors. AB - Clonal cell analysis defines the potential of single cells and the diversity they can produce. To achieve this, we have developed a novel adaptation of the genetic tracing strategy, UbC-StarTrack, which attributes a specific and unique color code to single neural precursors, allowing all their progeny to be tracked. We used integrable fluorescent reporters driven by a ubiquitous promoter in PiggyBac based vectors to achieve inheritable and stable clonal cell labeling. In addition, coupling this to an inducible Cre-LoxP system avoids the expression of non-integrated reporters. To assess the utility of this system, we first analyzed images of combinatorial expression of fluorescent reporters in transfected cells and their progeny. We also validated the efficiency of the UbC-StarTrack to trace cell lineages through in vivo, in vitro and ex vivo strategies. Finally, progenitors located in the lateral ventricles were targeted at embryonic or postnatal stages to determine the diversity of neurons and glia they produce, and their clonal relationships. In this way we demonstrate that UbC-StarTrack can be used to identify all the progeny of a single cell and that it can be employed in a wide range of contexts. PMID- 27654511 TI - Cyclooxygenase-2 induced beta1-integrin expression in NSCLC and promoted cell invasion via the EP1/MAPK/E2F-1/FoxC2 signal pathway. AB - Cyclooxygenase-2 (COX-2) has been implicated in cell invasion in non-small-cell lung cancer (NSCLC). However, the mechanism is unclear. The present study investigated the effect of COX-2 on beta1-integrin expression and cell invasion in NSCLC. COX-2 and beta1-integrin were co-expressed in NSCLC tissues. COX-2 overexpression or Prostaglandin E2 (PGE2) treatment increased beta1-integrin expression in NSCLC cell lines. beta1-integrin silencing suppressed COX-2 mediated tumour growth and cancer cell invasion in vivo and in vitro. Prostaglandin E Receptor EP1 transfection or treatment with EP1 agonist mimicked the effect of PGE2 treatment. EP1 siRNA blocked PGE2-mediated beta1-integrin expression. EP1 agonist treatment promoted Erk1/2, p38 phosphorylation and E2F-1 expression. MEK1/2 and p38 inhibitors suppressed EP1-mediated beta1-integrin expression. E2F-1 silencing suppressed EP1-mediated FoxC2 and beta1-integrin upregulation. ChIP and Luciferase Reporter assays identified that EP1 agonist treatment induced E2F-1 binding to FoxC2 promotor directly and improved FoxC2 transcription. FoxC2 siRNA suppressed beta1-integrin expression and EP1-mediated cell invasion. Immunohistochemistry showed E2F-1, FoxC2, and EP1R were all highly expressed in the NSCLC cases. This study suggested that COX-2 upregulates beta1 integrin expression and cell invasion in NSCLC by activating the MAPK/E2F-1 signalling pathway. Targeting the COX-2/EP1/PKC/MAPK/E2F-1/FoxC2/beta1-integrin pathway might represent a new therapeutic strategy for the prevention and treatment of this cancer. PMID- 27654512 TI - Enhancement of anaerobic digestion of grass by pretreatment with imidazolium based ionic liquids. AB - In this work, the toxicity of imidazolium-based ionic liquids (ILs) and the enhancement of high-solid anaerobic digestion by pretreatment were studied. Compared with [Bmim]Cl, [Bmim]OAc and [Bmim]BF4, [Bmim]PF6 had the highest toxicity. When the mass ratio of [Bmim]PF6 to grass was higher than 1:10, biogas was not produced within 30 days. The ability to remove lignin and hemicellulose followed the sequence of [Bmim]OAc, [Bmim]Cl, [Bmim]BF4 and [Bmim]PF6. The crystallinity index of grass pretreated with [Bmim]OAc, [Bmim]Cl, [Bmim]BF4 and [Bmim]PF6 reduced by 73.83%, 54.44%, 17.52% and 7.47%, respectively. The pretreatment with ILs enhanced the methane yield of grass by reducing crystallinity and particle size. The grass pretreated with [Bmim]OAc had the highest methane yield, about 221 mL/g volatile solids, due to its good lignin removal ability and relative low toxicity. After 10 times recycling, the cumulative methane yield of grass pretreated by recycled [Bmim]OAc decreased by 11.95%. PMID- 27654513 TI - Erratum. PMID- 27654514 TI - NOR-1/NR4A3 regulates the cellular inhibitor of apoptosis 2 (cIAP2) in vascular cells: role in the survival response to hypoxic stress. AB - Vascular cell survival is compromised under pathological conditions such as abdominal aortic aneurysm (AAA). We have previously shown that the nuclear receptor NOR-1 is involved in the survival response of vascular cells to hypoxia. Here, we identify the anti-apoptotic protein cIAP2 as a downstream effector of NOR-1. NOR-1 and cIAP2 were up-regulated in human AAA samples, colocalizing in vascular smooth muscle cells (VSMC). While NOR-1 silencing reduced cIAP2 expression in vascular cells, lentiviral over-expression of this receptor increased cIAP2 mRNA and protein levels. The transcriptional regulation of the human cIAP2 promoter was analyzed in cells over-expressing NOR-1 by luciferase reporter assays, electrophoretic mobility shift analysis and chromatin immunoprecipitation, identifying a NGFI-B site (NBRE-358/-351) essential for NOR 1 responsiveness. NOR-1 and cIAP2 were up-regulated by hypoxia and by a hypoxia mimetic showing a similar time-dependent pattern. Deletion and site-directed mutagenesis studies show that NOR-1 mediates the hypoxia-induced cIAP2 expression. While NOR-1 over-expression up-regulated cIAP2 and limited VSMC apoptosis induced by hypoxic stress, cIAP2 silencing partially prevented this NOR 1 pro-survival effect. These results indicate that cIAP2 is a target of NOR-1, and suggest that this anti-apoptotic protein is involved in the survival response to hypoxic stress mediated by NOR-1 in vascular cells. PMID- 27654515 TI - Outbreaks of colistin-resistant and colistin-susceptible KPC-producing Klebsiella pneumoniae in a Brazilian intensive care unit. AB - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE), especially those that produce Klebsiella pneumoniae carbapenemase (KPC) and are associated with colistin resistance, pose a severe health threat due to the limited treatment options. AIM: To describe two outbreaks of KPC-producing K. pneumoniae in an adult intensive care unit (AICU) in Brazil. In May 2015, 14 patients had colistin susceptible KPC-producing strains (ColS-KPC), and in July 2015, nine patients had colistin-resistant KPC-producing strains (ColR-KPC). METHODS: Between September 2014 and August 2015, we performed surveillance at a university hospital and all CRE were tested for blaKPC genes. Clonality was investigated by pulsed-field gel electrophoresis. Resistance to colistin was confirmed by broth microdilution method. Consumption of carbapenems and colistin was expressed as defined daily doses. FINDINGS: In all, 111 patients with CRE were identified during the surveillance period; K. pneumoniae was the major isolate (77.13%). The two outbreaks were identified when infection rates (KPC per 1000 patient-days) exceeded the background level. Rates of carbapenem and colistin consumption were high. Control measures (bedside alcohol gel, contact precautions, regular rectal swabs) did not curtail the outbreaks. Mortality rates were 42.9% and 44.4% for ColS-KPC- and ColR-KPC-infected patients, respectively. After the death of four infected patients with ColR-KPC, the unit was closed to new admissions. CONCLUSION: Our experience demonstrates the serious risks presented by KPC, and especially ColR-KPC, in Brazilian AICUs. Selective pressure from excessive antibiotic use and transmission on healthcare workers' hands were likely the major factors in transmission. PMID- 27654516 TI - Corrigendum: Screening for protein-protein interactions using Forster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM). PMID- 27654517 TI - Our exclusive survey of nurse directors reveals worrying turnover statistics. AB - Nursing Standard's annual survey of nurse directors has revealed that turnover in the boardrooms of trusts and health boards continues to be at worrying levels. PMID- 27654518 TI - A banner year. AB - A special service has been held at York Minster to mark 100 years of the RCN. PMID- 27654519 TI - Mentors 'manipulated, even threatened' by some students. AB - Placement mentors are being 'manipulated' and some even subjected to violent threats by nursing students, new research reveals. PMID- 27654520 TI - Ebola nurse 'relieved' after NMC clears her of misconduct in airport screening process. AB - Scottish nurse Pauline Cafferkey (pictured right), who recovered from the Ebola virus, spoke of her relief after being cleared of misconduct by the Nursing and Midwifery Council. PMID- 27654522 TI - Staff cuts leave FGM vulnerable 'exposed'. AB - School nursing cuts and workforce pressures are hampering efforts to end female genital mutilation (FGM). PMID- 27654523 TI - 'Come back' letter sent to 54,000 former registrants. AB - Letters have been sent to tens of thousands of former practising nurses in England urging them to return to the profession. PMID- 27654525 TI - Pension opt-out scheme 'immoral', say unions. AB - Unions organised a protest at an NHS hospital over 'morally wrong' plans to allow nurses to opt out of their pension in exchange for a higher salary. PMID- 27654528 TI - Support is in decline for families affected by abuse. AB - Two in five health visitors say support for families affected by domestic abuse in England has declined in the past 2 years. PMID- 27654526 TI - Nurse-led end of life care centre could save the NHS L350,000 each year. AB - A nurse-led end of life care service has led to fewer hospital admissions and could save the NHS L350,000 a year, an independent review has found. PMID- 27654529 TI - Trusts are struggling to retain chief nurses. AB - An analysis of 230 English NHS trusts, 14 Scottish and seven Welsh health boards found 132 (53%) chief nurses had only been in post since 2014. Of this figure, 33 nurse directors took up their new positions this year. PMID- 27654532 TI - Managing obesity in adults and children. AB - Essential facts According to the Health Survey for England, in 2013 about a quarter of adults were obese, while 41% of men and 33% of women were overweight. PMID- 27654533 TI - Taking vitamin D could halve the risk of asthma attacks. AB - Cochrane library research has found that giving a daily oral vitamin D supplement to people with mild to moderate asthma reduced the risk of severe attacks requiring hospital admission or emergency department attendance from 6% to about 3%. PMID- 27654534 TI - Economic crisis prompts rise in suicides and mental ill health. AB - Recessions are bad for you, especially if you're a man aged 25-44. That's the conclusion of a systematic review of studies into the effects on health of the 2008 banking meltdown. PMID- 27654535 TI - Irregular heartbeat associated with wide range of serious events. AB - In collaboration with researchers from the Massachusetts Institute of Technology in the United States, the researchers analysed the results of 104 studies involving nine million participants, 587,867 of whom were diagnosed with atrial fibrillation (AF). PMID- 27654536 TI - Near-infrared light could detect early cancer signs. AB - Scientists have developed an endoscope which can distinguish between light emitted by healthy and abnormal cells. PMID- 27654537 TI - 'Evidence for binge drinking pill does not justify cost to NHS'. AB - There is 'no direct evidence' to support the effectiveness of nalmefene, the drug approved for use in the NHS in England by the National Institute for Health and Care Excellence (NICE) to curb excess drinking among those who are alcohol dependent. PMID- 27654538 TI - A roadmap for mental health. AB - The Five Year Forward View could be a turning point in the battle to get mental health parity with physical health, address long waiting times and unmet need, and ensure people get care close to home. PMID- 27654539 TI - On the right track. AB - Sarah Ingleby, lead nurse for the acute care and hospital at night teams at Central Manchester University Hospitals NHS Foundation Trust (CMFT), says the Patientrack handheld electronic system has helped staff to identify, manage and treat sepsis. PMID- 27654540 TI - Succeed at the confirmer stage of revalidation. AB - Being a confirmer is one way for nurses to learn from their peers. It is common for the revalidating nurse to want to go through the confirmation process with someone they know and feel comfortable with. There can be a level of nervousness surrounding revalidation but, as practice nurse Sarah Alexander advises, the best way to avoid being anxious is to allow plenty of time for the process. PMID- 27654541 TI - District nursing needs to be thrown a lifeline. AB - There is a profound and growing gap between capacity and demand in district nursing, jeopardising the quality of patient care. PMID- 27654542 TI - Is it okay to buy an essay online? AB - There is no legal, ethical or professional reason why you should not buy an essay to help with your assessments - it is the same as buying a book. However, it is not the purchase of the essay that needs consideration, it is what you are going to use it for. PMID- 27654543 TI - Health visiting cuts only save problems for later. AB - It feels as inevitable as the turning of the leaves - that time of year when winter pressures begin to loom, as staff shortages and cuts to training places become more apparent. PMID- 27654544 TI - Supporting blind veterans. AB - The national charity Blind Veterans UK supports blind or partially sighted ex service men and women, providing them with a wide range of practical and emotional support. PMID- 27654545 TI - Crisis in emergency care. AB - In the past two decades, the problem of bed shortages and emergency departments under pressure has increased in intensity. More than 25 years ago, when the seeds of today's problems were sown, we were told that it would be okay to reduce bed numbers because community and social services would be improved. PMID- 27654546 TI - New idea for student funding. AB - Scrapping the student bursary will have a negative impact on the profession. I studied nursing from 2007-10 and most of my class was 'mature', with only a few students aged 23 or under. Most of the mature students had children and spouses, and mortgages and bills to pay. PMID- 27654549 TI - Nothing to fear from CQC. AB - When Care Quality Commission inspections are looming, organisations rightly work hard to be ready. But if staff are already doing what they should be doing then there is no need to behave any differently under the gaze of the inspectors. The CQC is about driving up standards, not blaming and shaming. It identifies the need for improvement but also highlights good practice. Let's embrace it, not be afraid of it. PMID- 27654550 TI - Hanging on the hospital telephone. AB - When someone dear to you is admitted to hospital in an emergency, you are not in a calm frame of mind. You want news, and fast. But when you call the hospital, the phone just keeps ringing. PMID- 27654551 TI - Readers' panel - Is the BMA playing politics in the junior doctors' dispute? AB - Our experts consider a hot topic of the day. PMID- 27654554 TI - Dermofit. AB - Developed by staff and students at Leeds Beckett University, this app aims to train clinical nurses and dermatology specialist nurses to detect skin cancer by identifying malignant and benign skin lesions and growths at an earlier stage. PMID- 27654555 TI - Student life - A multisensory approach. AB - As a registered nurse, you will be expected to assess each individual and provide holistic patient care. As simple as this sounds, it isn't always easy, and you will quickly learn that no two patients are the same. PMID- 27654556 TI - Observing nurses has improved my alcohol dependency care. AB - My first placement in my first year of nursing training was on a gastrointestinal/hepatology ward. Alongside my mentor, I was caring for a patient who had been withdrawing from alcohol since admission to hospital the previous evening. PMID- 27654557 TI - Doing night shifts: the good, the bad and just coping. AB - Working night shifts can play havoc with a person's health and well-being. Research published in April found that female nurses in the United States, who worked rotating night shifts for 10 years or longer, had a 15% or higher increased risk of coronary heart disease compared with women who did not work night shifts. PMID- 27654558 TI - 'My band 8 role keeps me close to patients'. AB - A charity-funded nursing post may be fulfilling, but is it a dead end for your career progression? PMID- 27654559 TI - Valuing mental health staff. AB - Ben Thomas is the mental health, learning disabilities and dementia care professional officer at the Department of Health (DH). He has held senior clinical, academic and management posts in England and Australia, and was a director of nursing. Before working at the DH, Ben was head of mental health and learning disabilities at the National Patient Safety Agency. He is a member of the RCNi editorial board. PMID- 27654560 TI - How to assess vision. AB - Rationale and key points An objective assessment of the patient's vision is important to assess variation from 'normal' vision in acute and community settings, to establish a baseline before examination and treatment in the emergency department, and to assess any changes during ophthalmic outpatient appointments. " Vision is one of the essential senses that permits people to make sense of the world. " Visual assessment does not only involve measuring central visual acuity, it also involves assessing the consequences of reduced vision. " Assessment of vision in children is crucial to identify issues that might affect vision and visual development, and to optimise lifelong vision. " Untreatable loss of vision is not an inevitable consequence of ageing. " Timely and repeated assessment of vision over life can reduce the incidence of falls, prevent injury and optimise independence. Reflective activity 'How to' articles can help update you practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How this article might change your practice when assessing people holistically. 2. How you could use this article to educate your colleagues in the assessment of vision. PMID- 27654561 TI - Supporting students in practice: leadership. AB - This article, the tenth in a series of 11, discusses the importance of effective leadership in nursing and how it can enhance the provision of high quality care. Recent findings regarding suboptimal care practices in nursing have demonstrated the need for effective leadership in healthcare settings. Mentors and practice teachers are required to demonstrate leadership as part of their nursing role and their role in facilitating student learning. In addition, mentors and practice teachers are responsible for developing effective leadership skills in students, who will be expected to demonstrate these skills when they become registered nurses or midwives. Guidance for mentors and practice teachers is provided in relation to the eighth domain and outcomes of the Standards to Support Learning and Assessment in Practice on leadership. PMID- 27654562 TI - Using the British National Formulary effectively. AB - Nursing students, nurses and other healthcare professionals involved in prescribing, dispensing, administration and monitoring of medicines should be able to navigate and use the British National Formulary (BNF) effectively. Recent changes to the structure of the BNF have resulted in new symbols, additional sections in drug and drug-class monographs, and a reduction in the amount of cross-referencing between chapters. This article explores how healthcare professionals can access the information in the BNF to ensure that medicines use is optimised, therapeutic effects are maximised, and adverse drug reactions and drug interactions are minimised. PMID- 27654563 TI - In-hospital resuscitation. AB - What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article outlined the response sequence required for cardiac arrest in an in-hospital environment and discussed effective cardiopulmonary resuscitation (CPR) and defibrillation. PMID- 27654564 TI - Sarah's support has helped me to tackle my eating disorder. AB - I first met Sarah Duffy when I attended the intensive eating disorder service at London's Royal Free Hospital. PMID- 27654565 TI - Online. AB - 'It is time we shared responsibility for tackling health inequality in our communities. Nurses are only part of the solution - citizens are the other'. PMID- 27654566 TI - Uncovering the real Broadmoor. AB - Can nurses use the example of Broadmoor to enhance their own practice? Stephanie Jones-Berry reports behind the scenes in England's most infamous psychiatric hospital. Contrary to the sensational tabloid stories, she discusses the hospital's supportive ethos. Ms Jones-Berry talks to Broadmoor nurses about how the hospital's inclusive approach helps service users overcome mental health issues and how nurses work collaboratively with patients. She also interviews a former high-risk service user whose experiences at Broadmoor allowed him to transition back into the community and is now involved with mandatory induction training for staff. PMID- 27654567 TI - Big picture. AB - An all-singing, all-dancing production on the challenge of cancer diagnosis is set to hit the stage in Manchester, Exeter and London. The show will look beyond poster campaigns and pink ribbons to the reality of family strain and altered bodies in a musical form. PMID- 27654568 TI - Nursing textbooks need to inform about spirituality. AB - Considering the spiritual needs of patients is an important aspect of holistic patient care. However, many nurses lack knowledge and awareness of the subject, and spirituality is not strongly featured as a key part of holistic care in core nursing textbooks. The author argues that guidance given by nursing textbooks needs to be more applicable to practice. PMID- 27654569 TI - Ways to develop numeracy and calculation skills. AB - Prescribing and administering medicines to children and young people is challenging, resulting in greater potential for error. This article aims to enhance children's nurses' knowledge and skills in medicines management, and help to address numeracy and calculation deficiencies. The activities throughout will help nurses develop and practise numeracy skills. PMID- 27654570 TI - Primary open-angle glaucoma. AB - Glaucoma is an optic neuropathy that is characterized by the progressive degeneration of the optic nerve, leading to visual impairment. Glaucoma is the main cause of irreversible blindness worldwide, but typically remains asymptomatic until very severe. Open-angle glaucoma comprises the majority of cases in the United States and western Europe, of which, primary open-angle glaucoma (POAG) is the most common type. By contrast, in China and other Asian countries, angle-closure glaucoma is highly prevalent. These two types of glaucoma are characterized based on the anatomic configuration of the aqueous humour outflow pathway. The pathophysiology of POAG is not well understood, but it is an optic neuropathy that is thought to be associated with intraocular pressure (IOP)-related damage to the optic nerve head and resultant loss of retinal ganglion cells (RGCs). POAG is generally diagnosed during routine eye examination, which includes fundoscopic evaluation and visual field assessment (using perimetry). An increase in IOP, measured by tonometry, is not essential for diagnosis. Management of POAG includes topical drug therapies and surgery to reduce IOP, although new therapies targeting neuroprotection of RGCs and axonal regeneration are under development. PMID- 27654571 TI - Investigations on aviadenoviruses isolated from turkey flocks in Germany. AB - During routine diagnosis in 2012, 69 samples of diseased turkey breeding and fattening flocks in Germany were examined for infection with aviadenoviruses by virus isolation using primary chicken embryo liver cells. In total, 21 aviadenovirus isolates, identified by a group-specific indirect immunofluorescence test, were obtained from 19 flocks. In almost all cases, molecular typing of these isolates based on partial hexon gene sequences revealed the presence of different types of turkey aviadenoviruses (TAdVs), including species Turkey aviadenovirus B (TAdV-B) with at least two different genotypes, as well as the species Turkey aviadenovirus C (TAdV-C) and Turkey aviadenovirus D (TAdV-D). Further analysis of DNA-dependent DNA polymerase gene sequences confirmed the classification of selected TAdV-C and TAdV-D isolates. Based on the results obtained for both genes, we suggest that TAdV-2, in addition to TAdV-4, belongs to the species TAdV-C. In contrast, amplification of the DNA polymerase gene fragment of nearly all investigated TAdV-B isolates failed due to unknown reasons. The results of sequence and phylogenetic analysis support the previously proposed classification of TAdVs into three different species and demonstrated how widely spread these viruses are in German turkey flocks. Analysis of case histories revealed a wide range of clinical and pathological changes; however an apparent link between types and disease conditions was not identified. PMID- 27654572 TI - Biomechanical, neuromuscular and knee pain effects following therapeutic knee taping among patients with knee osteoarthritis during walking gait. AB - BACKGROUND: Knee osteoarthritis is one of the most debilitating diseases associated with aging, and is estimated to affect 9% of men and 18% of women over 65years of age. Knee osteoarthritis affects the condylar surfaces of the joint and if left untreated generally leads to the slow and painful degeneration of the joint and surrounding structures. With few non-invasive treatment options for osteoarthritis patients, this study investigated the effect of therapeutic taping on knee pain in combination with spatiotemporal, kinematic, kinetic and muscle activation measures. METHODS: Fifteen participants (10 male, 5 female) with radiographic diagnosed knee osteoarthritis attended a single testing session and walked along at a self-selected pace under three different conditions (no tape, sham tape, therapeutic tape). The conditions were randomised within each testing session. Knee pain, lower limb biomechanics and muscle activation were analysed using a one-way repeated measures ANOVA to determine if any differences existed between the three taping conditions (alpha=0.05). FINDINGS: Therapeutic knee taping was shown to significantly reduce the self-reported levels of knee joint pain during straight line walking. No significant differences in spatiotemporal, knee kinetic, knee kinematic or lower limb muscle activation variables were observed between the taping conditions. INTERPRETATION: There is evidence supporting the use of therapeutic knee taping for the management of osteoarthritis related knee pain. Future research is recommended to better understand the complex acute neuro-musculoskeletal adaptations that explain these positive knee pain findings. PMID- 27654573 TI - Efficacy of resistin and leptin in predicting persistent organ failure in patients with acute pancreatitis. AB - BACKGROUND: To investigate the accuracy of resistin, leptin and adiponectin levels in predicting persistent organ failure in patients with acute pancreatitis (AP). METHODS: Data from 90 consecutive patients admitted to our hospital for AP were retrospectively collected from an ongoing prospective cohort study. The levels of adiponectin, leptin and resistin were measured and compared between patients with and without persistent organ failure. The accuracy of the adipokines in predicting persistent organ failure were compared with the patients' Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, and were separately investigated in overweight and non-overweight groups. RESULTS: Persistent organ failure occurred in 26.7% of the patients. The levels of resistin were significantly increased in AP patients with persistent organ failure, in both the overweight and the non-overweight subgroups. Resistin and APACHE-II score predicted persistent organ failure with comparable areas under the curve (AUC) of 0.72 and 0.75, respectively (p = 0.66). Resistin demonstrated similar accuracy with the APACHE-II score in predicting persistent organ failure in the overweight (0.69 vs. 0.66, p = 0.82) and non-overweight (0.76 vs. 0.87, p = 0.39) subgroups. There was no correlation between adiponectin and persistent organ failure, but a weak correlation between leptin and persistent organ failure was demonstrated. CONCLUSIONS: Resistin and leptin levels, rather than adiponectin, correlate with persistent organ failure in patients with AP. PMID- 27654574 TI - Nerve growth factor regulates CD133 function to promote tumor cell migration and invasion via activating ERK1/2 signaling in pancreatic cancer. AB - BACKGROUND: Perineural invasion (PNI) is extremely high frequency among the various metastatic routes in pancreatic cancer. Nerve growth factor, secreted by astroglial cells, exerts effects on tumor invasion in some cancer cells, but its function on migration and invasion in pancreatic cancer is still unclear. In the present study, we determined the effects of NGF on modulating tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. METHODS: NGF and CD133 expression were detected in tumor tissues using immunohistochemical analysis and Western blotting analysis. The effects of NGF on the regulation of CD133 expression and the promotion of cancer migration and invasion were investigated using wound healing and matrigel transwell assay. A related mechanism that NGF regulates CD133's function via activating ERK1/2 signaling also was observed. RESULTS: NGF/CD133 is overexpressed in human pancreatic cancer and promotes the migration and invasion of human pancreatic cancer cells through the activation of the ERK/CD133 signaling cascade. NGF/ERK signaling modulates the cancer cell EMT process, migration and invasion through the regulation of CD133 expression and its subcellular localization. CONCLUSIONS: NGF/CD133 signaling initiated the migration and invasion of pancreatic cancer cells. NGF/CD133 might be an effective and potent therapeutic target for pancreatic cancer metastasis, particularly in PNI. PMID- 27654575 TI - Biodegradable Porous Starch Spheres as a Novel Carrier for Enhancement of Dissolution Rate and Oral Bioavailability of Itraconazole. AB - BACKGROUND: A biodegradable porous starch (BPS) was developed in order to improve dissolution and oral bioavailability of Itraconazole as a poorly water-soluble antifungal drug. METHOD: BPS was developed by converting native starch from hydrogel to alcogel by solvent exchange method. The developed BPS carrier was characterized by SEM and nitrogen adsorption/desorption analysis to understand surface morphology and porosity distribution respectively. Itraconazole (ITR) was loaded on BPS by adsorption mediated solvent evaporation method, which provides a hydrophilic matrix powder. This causes drug distribution within hydrophilic matrix of porous starch. RESULTS: Solid-state characterization of optimized batch (ITR/BPS-3) was performed using DSC, PXRD, FTIR, SEM and FTIR chemical imaging. In vitro dissolution and in vivo pharmacokinetic studies were performed to evaluate therapeutic potential of ITR/BPS-3 system. In vitro studies of ITR: BPS 3 system revealed a burst effect in drug release (93%) compared to marketed product, which showed 90% drug release at the end of 60 min compared to 84% of marketed. Moreover, ITR/BPS-3 system showed improved oral bioavailability up to 3.93 fold and marketed product shows 3.12 fold compared to ITR. CONCLUSION: This effect is due to high surface area, improved wettability and reduced crystallinity of ITR due to its adsorption into BPS. A successful methodology was reported to prepare BPS from raw starch. PMID- 27654576 TI - Enhanced Bioavailability of Curcumin Nanoemulsions Stabilized with Phosphatidylcholine Modified with Medium Chain Fatty Acids. AB - BACKGROUND: Curcumin is a natural, oil-soluble polyphenolic compound with potent anticancer, anti-inflammatory, and antioxidant activities. In its free form, it is very poorly absorbed in the gut due to its very low solubility. The use of nanoemulsions as carrier is a feasible way for improving curcumin bioavailability. To this end, the choice of emulsifying agent for stabilizing the nanoemulsions is of the upmost importance for achieving a desired functionality. METHODS: Phosphatidylcholine (PC) and phosphatidycholine enriched (PCE) with medium chain fatty acids (42.5 mol %) in combination with glycerol as co surfactant, were used for preparing oil-in water nanoemulsions coded as NEPC and NEPCE, respectively. RESULTS: NEPCE displayed significantly smaller mean droplet size (30 nm), equal entrapment efficiency (100%), better droplet stability and suffered lower encapsulation efficiency loss (3%) during storage time (120 days, 4oC) than NEPC. Bioavailability, measured in terms of area under the curve of curcumin concentration versus time, and maximum curcumin plasma concentration, was in general terms significantly higher for NEPCE than for NEPC, and for curcumin coarse aqueous suspension (CCS). Also, NEPCE produced significantly higher curcumin concentrations in liver and lung than NEPC and CCS. CONCLUSION: These data support the role of phosphatidylcholine enriched with medium chain fatty acids to increase the bioavailability of nanoemulsions for therapeutic applications. PMID- 27654577 TI - Modeling Liquid Photoemission Spectra: Path-Integral Molecular Dynamics Combined with Tuned Range-Separated Hybrid Functionals. AB - We present a computational protocol for modeling valence photoemission spectra of liquids. We use water as an experimentally well-characterized model system, and we represent its liquid state by larger finite-sized droplets. The photoemission spectrum is evaluated for an ensemble of structures along molecular dynamics simulations. The nuclear quantum effects are accounted for by ab initio based path-integral molecular dynamics simulations that are greatly accelerated with the so-called colored noise thermostat (PI+GLE) method. The ionization energies for the valence electrons are evaluated as orbital energies of optimally tuned range-separated hybrid functionals (OT-RSH). This approach provides Koopmans-type ionization energies including relaxation energy. We show that the present protocol can quantitatively describe the valence photoemission spectrum of liquid water, i.e., the positions, shapes, and widths of the photoemission peaks. With the PI+GLE simulations, even the subtle isotope effects that have been recently observed experimentally can be modeled. The electronic properties of finite-sized droplets are shown to converge rapidly to those of liquids. We discuss the importance of proper tuning of the range-separation parameter in OT-RSH as well as possible sources of error in our simulations. The present approach seems to be a viable route to modeling photoemission spectra of liquids, especially in conjunction with efficient implementation of density functional methods on graphical processing units. PMID- 27654578 TI - Giant dedifferentiated liposarcoma of small bowel mesentery: a case report. AB - BACKGROUND: Dedifferentiated liposarcoma is an uncommon variant of liposarcoma, with poor prognosis and higher preponderance to local recurrence. Only nine cases of dedifferentiated liposarcoma of small bowel mesentery have been reported till now. This is a case of giant dedifferentiated liposarcoma of the small bowel mesentery, weighing nearly 9 kg (19.8 lbs), with synchronous lesions in the extraperitoneal space, which is the first such case to be reported. CASE PRESENTATION: We report a case of a 62-year-old man, who presented with a huge abdominal mass occupying nearly the entire abdomen. A contrast enhanced computed tomography of abdomen and pelvis revealed a large, poorly enhancing, heterogeneous, lobulated mass of size 27 * 16 cm, displacing the bowel loops peripherally. At laparotomy, a large mass arising from the small bowel mesentery was found. In addition, many other smaller synchronous lesions were studded in the entire small bowel mesentery and a couple more in the extraperitoneal space. A palliative excision of the giant mass along with the adjacent small bowel was done. The other smaller swellings were not causing any mass effect and were left behind as they were numerous, virtually ruling out any possibility of a curative excision. The histopathological examination suggested the diagnosis of dedifferentiated liposarcoma. On immunohistochemistry, S-100 was positive in the well-differentiated sarcomatous areas. The CD 117 and SMA were strongly negative ruling out the possibility of a gastrointestinal stromal tumour. The CD 34 however was positive in the tumour cells. CONCLUSIONS: Dedifferentiated liposarcoma of the small bowel mesentery is rare. Involvement of nearly whole of the small bowel mesentery in the disease process virtually rules out the possibility of a curative resection, the mainstay of management. This report would add to the knowledge of this rare disease and the possible therapeutic problem that may be encountered in case of multifocal disease. PMID- 27654579 TI - Hypomethylating agent combination strategies in myelodysplastic syndromes: hopes and shortcomings. AB - The hypomethylating agents (HMA) azacitidine and decitabine are both approved by the FDA for the treatment of myelodysplastic syndromes (MDS). Although heralded as a significant advancement, HMA lead to responses in less than half of patients and for those that respond most will relapse. As such, there is a crucial need to improve frontline therapy approaches. One promising strategy involves combining azacitidine or decitabine with investigational or existing therapies with the goal of achieving synergistic activity and better patient outcomes. The purpose of this paper is to critically review the efficacy and safety of reported HMA based combination regimens in patients with higher-risk MDS. PMID- 27654580 TI - A hybrid expectation maximisation and MCMC sampling algorithm to implement Bayesian mixture model based genomic prediction and QTL mapping. AB - BACKGROUND: Bayesian mixture models in which the effects of SNP are assumed to come from normal distributions with different variances are attractive for simultaneous genomic prediction and QTL mapping. These models are usually implemented with Monte Carlo Markov Chain (MCMC) sampling, which requires long compute times with large genomic data sets. Here, we present an efficient approach (termed HyB_BR), which is a hybrid of an Expectation-Maximisation algorithm, followed by a limited number of MCMC without the requirement for burn in. RESULTS: To test prediction accuracy from HyB_BR, dairy cattle and human disease trait data were used. In the dairy cattle data, there were four quantitative traits (milk volume, protein kg, fat% in milk and fertility) measured in 16,214 cattle from two breeds genotyped for 632,002 SNPs. Validation of genomic predictions was in a subset of cattle either from the reference set or in animals from a third breeds that were not in the reference set. In all cases, HyB_BR gave almost identical accuracies to Bayesian mixture models implemented with full MCMC, however computational time was reduced by up to 1/17 of that required by full MCMC. The SNPs with high posterior probability of a non-zero effect were also very similar between full MCMC and HyB_BR, with several known genes affecting milk production in this category, as well as some novel genes. HyB_BR was also applied to seven human diseases with 4890 individuals genotyped for around 300 K SNPs in a case/control design, from the Welcome Trust Case Control Consortium (WTCCC). In this data set, the results demonstrated again that HyB_BR performed as well as Bayesian mixture models with full MCMC for genomic predictions and genetic architecture inference while reducing the computational time from 45 h with full MCMC to 3 h with HyB_BR. CONCLUSIONS: The results for quantitative traits in cattle and disease in humans demonstrate that HyB_BR can perform equally well as Bayesian mixture models implemented with full MCMC in terms of prediction accuracy, but with up to 17 times faster than the full MCMC implementations. The HyB_BR algorithm makes simultaneous genomic prediction, QTL mapping and inference of genetic architecture feasible in large genomic data sets. PMID- 27654581 TI - Endoplasmic reticulum (ER) stress triggers Hax1-dependent mitochondrial apoptotic events in cardiac cells. AB - Cardiomyocyte apoptosis is a major process in pathogenesis of a number of heart diseases, including ischemic heart diseases and cardiac failure. Ensuring survival of cardiac cells by blocking apoptotic events is an important strategy to improve cardiac function. Although the role of ER disruption in inducing apoptosis has been demonstrated, we do not yet fully understand how it influences the mitochondrial apoptotic machinery in cardiac cell models. Recent investigations have provided evidences that the prosurvival protein HCLS1 associated protein X-1 (Hax1) protein is intimately associated with the pathogenesis of heart disease, mitochondrial biology, and protection from apoptotic cell death. To study the role of Hax1 upon ER stress induction, Hax1 was overexpressed in cardiac cells subjected to ER stress, and cell death parameters as well as mitochondrial alterations were examined. Our results demonstrated that the Hax1 is significantly downregulated in cardiac cells upon ER stress induction. Moreover, overexpression of Hax1 protected from apoptotic events triggered by Tunicamycin-induced ER stress. Upon treatment with Tunicamycin, Hax1 protected from mitochondrial fission, downregulation of mitofusins 1 and 2 (MFN1 and MFN2), loss of mitochondrial membrane potential (?Psim), production of reactive oxygen species (ROS) and apoptotic cell death. Taken together, our results suggest that Hax1 inhibits ER stress-induced apoptosis at both the pre- and post-mitochondrial levels. These findings may offer an opportunity to develop new agents that inhibit cell death in the diseased heart. PMID- 27654582 TI - Ultra-Low-Dose Ultrasound Molecular Imaging for the Detection of Angiogenesis in a Mouse Murine Tumor Model: How Little Can We See? AB - OBJECTIVES: The objective of this study was to evaluate the minimum microbubble dose for ultrasound molecular imaging to achieve statistically significant detection of angiogenesis in a mouse model. MATERIALS AND METHODS: The preburst minus postburst method was implemented on a Verasonics ultrasound research scanner using a multiframe compounding pulse inversion imaging sequence. Biotinylated lipid (distearoyl phosphatidylcholine-based) microbubbles that were conjugated with antivascular endothelial growth factor 2 (VEGFR2) antibody (MBVEGFR2) or isotype control antibody (MBControl) were injected into mice carrying adenocarcinoma xenografts. Different injection doses ranging from 5 * 10 to 1 * 10 microbubbles per mouse were evaluated to determine the minimum diagnostically effective dose. RESULTS: The proposed imaging sequence was able to achieve statistically significant detection (P < 0.05, n = 5) of VEGFR2 in tumors with a minimum MBVEGFR2 injection dose of only 5 * 10 microbubbles per mouse (distearoyl phosphatidylcholine at 0.053 ng/g mouse body mass). Nonspecific adhesion of MBControl at the same injection dose was negligible. In addition, the targeted contrast ultrasound signal of MBVEGFR2 decreased with lower microbubble doses, whereas nonspecific adhesion of MBControl increased with higher microbubble doses. CONCLUSIONS: The dose of 5 * 10 microbubbles per animal is now the lowest injection dose on record for ultrasound molecular imaging to achieve statistically significant detection of molecular targets in vivo. Findings in this study provide us with further guidance for future developments of clinically translatable ultrasound molecular imaging applications using a lower dose of microbubbles. PMID- 27654584 TI - Caecal ulceration in an asymptomatic man. PMID- 27654583 TI - Ex vivo study of human visceral nociceptors. AB - OBJECTIVE: The development of effective visceral analgesics free of deleterious gut-specific side effects is a priority. We aimed to develop a reproducible methodology to study visceral nociception in human tissue that could aid future target identification and drug evaluation. DESIGN: Electrophysiological (single unit) responses of visceral afferents to mechanical (von Frey hair (VFH) and stretch) and chemical (bradykinin and ATP) stimuli were examined. Thus, serosal afferents (putative nociceptors) were used to investigate the effect of tegaserod, and transient receptor potential channel, vanilloid 4 (TRPV4) modulation on mechanical responses. RESULTS: Two distinct afferent fibre populations, serosal (n=23) and muscular (n=21), were distinguished based on their differences in sensitivity to VFH probing and tissue stretch. Serosal units displayed sensitivity to key algesic mediators, bradykinin (6/14 units tested) and ATP (4/10), consistent with a role as polymodal nociceptors, while muscular afferents are largely insensitive to bradykinin (0/11) and ATP (1/10). Serosal nociceptor mechanosensitivity was attenuated by tegaserod (-20.8+/-6.9%, n=6, p<0.05), a treatment for IBS, or application of HC067047 (-34.9+/-10.0%, n=7, p<0.05), a TRPV4 antagonist, highlighting the utility of the preparation to examine the mechanistic action of existing drugs or novel analgesics. Repeated application of bradykinin or ATP produced consistent afferent responses following desensitisation to the first application, demonstrating their utility as test stimuli to evaluate analgesic activity. CONCLUSIONS: Functionally distinct subpopulations of human visceral afferents can be demonstrated and could provide a platform technology to further study nociception in human tissue. PMID- 27654585 TI - Building pancreatic organoids to aid drug development. PMID- 27654587 TI - Errors in the Text and Supplement. PMID- 27654590 TI - Portrait of Virginia: Frida Kahlo. PMID- 27654586 TI - Gut microbiota and Toll-like receptors set the stage for cytokine-mediated failure of antibacterial responses in the fibrotic liver. PMID- 27654592 TI - WHO Declares India Free of Yaws and Maternal and Neonatal Tetanus. PMID- 27654591 TI - El Nino's Impact on Children. PMID- 27654593 TI - Psychological Scars From Conflict in South Sudan Documented. PMID- 27654594 TI - Injectable Diabetes Drug Approved. PMID- 27654595 TI - Kratom Products Seized. PMID- 27654596 TI - FDA Enlists Physicians' Aid. PMID- 27654597 TI - Ensuring Respect for Human Research Participants: Institutional Review Boards and Sharing Results From Research. PMID- 27654598 TI - Increasing the Value of Social Comparisons of Physician Performance Using Norms. PMID- 27654599 TI - Does It Matter?: And Other Unforgiving Rhetoric. PMID- 27654600 TI - Early Allergen Introduction for Preventing Development of Food Allergy. PMID- 27654601 TI - Introducing JAMA Performance Improvement. PMID- 27654602 TI - Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss: The IDEA Randomized Clinical Trial. AB - Importance: Effective long-term treatments are needed to address the obesity epidemic. Numerous wearable technologies specific to physical activity and diet are available, but it is unclear if these are effective at improving weight loss. Objective: To test the hypothesis that, compared with a standard behavioral weight loss intervention (standard intervention), a technology-enhanced weight loss intervention (enhanced intervention) would result in greater weight loss. Design, Setting, Participants: Randomized clinical trial conducted at the University of Pittsburgh and enrolling 471 adult participants between October 2010 and October 2012, with data collection completed by December 2014. Interventions: Participants were placed on a low-calorie diet, prescribed increases in physical activity, and had group counseling sessions. At 6 months, the interventions added telephone counseling sessions, text message prompts, and access to study materials on a website. At 6 months, participants randomized to the standard intervention group initiated self-monitoring of diet and physical activity using a website, and those randomized to the enhanced intervention group were provided with a wearable device and accompanying web interface to monitor diet and physical activity. Main Outcomes and Measures: The primary outcome of weight was measured over 24 months at 6-month intervals, and the primary hypothesis tested the change in weight between 2 groups at 24 months. Secondary outcomes included body composition, fitness, physical activity, and dietary intake. Results: Among the 471 participants randomized (body mass index [BMI], 25 to <40; age range, 18-35 years; 28.9% nonwhite, 77.2% women), 470 (233 in the standard intervention group, 237 in the enhanced intervention group) initiated the interventions as randomized, and 74.5% completed the study. For the enhanced intervention group, mean base line weightwas 96.3 kg (95% CI, 94.2-98.5) and 24 month weight 92.8 kg (95% CI, 90.6-95.0) [corrected]. For the standard intervention group, mean baseline weight was 95.2kg (95%CI,93.0-97.3)and24-month weight was 89.3 kg (95%CI, 87.1-91.5) [corrected].Weight change at 24 months differed significantly by intervention group (estimated mean weight loss, 3.5 kg [95% CI, 2.6-4.5} in the enhanced intervention group and 5.9 kg [95% CI, 5.0-6.8] in the standard intervention group; difference, 2.4 kg [95% CI, 1.0-3.7]; P = .002). Both groups had significant improvements in body composition, fitness, physical activity, and diet, with no significant difference between groups. Conclusions and Relevance: Among young adults with a BMI between 25 and less than 40, the addition of a wearable technology device to a standard behavioral intervention resulted in less weight loss over 24 months. Devices that monitor and provide feedback on physical activity may not offer an advantage over standard behavioral weight loss approaches. Trial Registration: clinicaltrials.gov Identifier: NCT01131871. PMID- 27654604 TI - Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis. AB - Importance: Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized. Objective: To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease. Data Sources: MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016. Study Selection: Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included. Data Extraction and Synthesis: Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence. Main Outcomes and Measures: Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis. Results: Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes. Conclusions and Relevance: In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies. PMID- 27654603 TI - Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial. AB - Importance: One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor alpha (TNF-alpha) inhibitors; little guidance on choosing the next treatment exists. Objective: To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. Design, Setting, and Participants: A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] >= 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. Interventions: Patients were randomly assigned (1:1) to receive a non-TNF targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. Main Outcomes and Measures: The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 <=3.2), remission (DAS28 <=2.6); serious adverse events; and serious infections. Results: Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28 ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). Conclusions and Relevance: Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. Trial Registration: clinicaltrials.gov Identifier: NCT01000441. PMID- 27654605 TI - Antimicrobial Resistance. AB - Importance: The development of antibiotics is considered among the most important advances of modern science. Antibiotics have saved millions of lives. However, antimicrobial resistance (AMR) threatens this progress and presents significant risks to human health. Objective: To identify factors associated with AMR, the current epidemiology of important resistant organisms, and possible solutions to the AMR problem. Data Sources, Study Selection, and Data Synthesis: PubMed (2000 2016), NIH REPORTER, and ClinicalTrials.gov databases were searched for articles and entries related to AMR, focusing on epidemiology, clinical effects of AMR, discovery of novel agents to treat AMR bacterial infections, and nonpharmacological strategies to eliminate or modify AMR bacteria. In addition to articles and entries found in these databases, selected health policy reports and public health guidance documents were reviewed. Of 217 articles, databases, and reports identified, 103 were selected for review. Results: The increase in AMR has been driven by a diverse set of factors, including inappropriate antibiotic prescribing and sales, use of antibiotics outside of the health care sector, and genetic factors intrinsic to bacteria. The problem has been exacerbated by inadequate economic incentives for pharmaceutical development of new antimicrobial agents. A range of specific AMR concerns, including carbapenem- and colistin-resistant gram-negative organisms, pose a clinical challenge. Alternative approaches to address the AMR threat include new methods of antibacterial drug identification and strategies that neutralize virulence factors. Conclusions and Relevance: Antimicrobial resistance poses significant challenges for current clinical care. Modified use of antimicrobial agents and public health interventions, coupled with novel antimicrobial strategies, may help mitigate the effect of multidrug-resistant organisms in the future. PMID- 27654606 TI - Pragmatic Trials: Practical Answers to "Real World" Questions. PMID- 27654607 TI - Performing the Wrong Procedure. PMID- 27654608 TI - Physician Capacity to Treat Opioid Use Disorder With Buprenorphine-Assisted Treatment. PMID- 27654609 TI - Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury. PMID- 27654610 TI - Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury. PMID- 27654611 TI - Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury. PMID- 27654612 TI - Guidelines for Tinnitus. PMID- 27654614 TI - Errors in Ratings Table. PMID- 27654613 TI - Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury-Reply. PMID- 27654615 TI - Error in Figure. PMID- 27654617 TI - Autumnal Equinox. PMID- 27654616 TI - Guidelines for Tinnitus-Reply. PMID- 27654618 TI - Scientific Inquisitiveness-An Anecdote. PMID- 27654619 TI - Types of Pancreatic Cysts. PMID- 27654620 TI - Fibrous Hamartoma of Infancy in the Eyelid: A Rare Presentation. AB - A 6-year-old girl presented with a left nodular mass around the punctum. Previous debulking in a similar location at 10 weeks and 8 months of age confirmed fibrous hamartoma of infancy. Pathology at the initial surgery revealed benign-appearing fibroadipose tissue, vasculature, and smooth muscle. Pathologic examination from the third debulking illustrated less fibrous trabeculae extending into increased amounts of mature-appearing adipocytes with collections of immature-appearing fibrocytes. The lesion had slight differences in pathology compared with prior surgical specimens; however, was still consistent with fibrous hamartoma of infancy. No recurrence has been reported since the last surgery. PMID- 27654621 TI - Association of Medical School Pediatric Department Chairs Principles of Lifelong Learning in Pediatric Medicine. AB - Pediatric general and subspecialty care requires continuous effort to maintain knowledge and competencies in clinical practice. Equally important are efforts by investigators and educators to maintain knowledge and competencies in the conduct of research and training. The Association of Medical School Pediatric Department Chairs initiated a survey in July 2015 to define principles of lifelong learning in pediatric medicine and determine the approaches and strategies used by chairs to assess knowledge and competence across the care, research, and teaching missions. A total of 101 of 142 chairs (71%) completed the survey. Six of 7 proposed principles were endorsed by 84% to 96% of Association of Medical School Pediatric Department Chairs members. The focus areas included individual accountability, individually relevant activities, use of evidence-based guidelines/national standards, gaining cognitive expertise, learning as a continuous effort, affordability, and focus on individual understanding. The chairs endorsed a requirement for evidence of lifelong learning, competence, and compliance by all faculty members in clinical (n = 89 [88%]), research (n = 63 [62%]), and educational (n = 85 [84%]) practice. The survey identified the strategies to assess lifelong learning and faculty competence and compliance in clinical, research, and educational roles. Across missions, chairs endorsed an expectation for individual responsibility supplemented by formal evaluation practices and institutional and regulatory office oversight. While chairs endorsed an important role for the American Board of Pediatrics in assessing and verifying lifelong learning, knowledge, and competence in general and specialty certification, most (n = 91 [90%]) endorsed a need to revise current board requirements to better emphasize closing gaps in knowledge and using approaches that are evidence-based. This study provides the perspectives of pediatric department chairs on principles for lifelong learning and strategies and approaches used to assess faculty competence and commitment to lifelong learning across missions. PMID- 27654622 TI - How Do Organizational Policies and Practices Affect Return to Work and Work Role Functioning Following a Musculoskeletal Injury? AB - Purpose Organizational-level policies and practices that promote safety leadership and practices, disability management and ergonomic policies and practices are considered key contextual determinants of return to work. Our objective was to examine the role of worker-reported organizational policies and practices (OPPs) in return to work (RTW) and work role functioning (WRF) and the mediating role of pain self-efficacy and work accommodation. Methods A worker cohort (n = 577) in Ontario, Canada was followed at 1, 6 and 12 months post injury. Both RTW (yes/no) and WRF (WLQ-16) status (3 levels) were measured. OPPs were measured (high vs. low) at 1 month post-injury. Pain self-efficacy (PSE) and work accommodation (WA) were included in mediation analyses. Results OPPs predicted RTW at 6 months (adjusted OR 1.77; 95 % CI 1.07-2.93) and 12 months (adjusted OR 2.07; 95 % CI 1.18-3.62). OPPs predicted WRF at 6 months, but only the transition from working with limitations to working without limitations (adjusted OR 3.21; 95 % CI 1.92-5.39). At 12 months, OPPs predicted both the transition from not working to working with and without limitations and from not working or working with limitations to working without limitations (adjusted OR 2.13; 95 % CI 1.37-3.30). Offers of WA mediated the relationship between OPPs and both RTW and WRF at 6 months follow-up. PSE mediated the relationship between OPPs and RTW and WRF at 6 months. At 12 months neither mediated the relationship. Conclusions The findings support worker-reported OPPs as key determinants of both RTW and WRF. These results point to the importance of WA and PSE in both RTW and WRF at 6 months. PMID- 27654623 TI - Frigoribacterium salinisoli sp. nov., isolated from saline soil, transfer of Frigoribacterium mesophilum to Parafrigoribacterium gen. nov. as Parafrigoribacterium mesophilum comb. nov. AB - A Gram-stain-positive, short-rod, aerobic bacterium, designated as strain LAM9155T, was isolated from saline soil sample collected from Lingxian County, Shandong Province, PR China. The strain grew optimally at 25-30 degrees C, pH 7.0 and 0.5 % (w/v) NaCl. The 16S rRNA gene sequence analysis revealed that strain LAM9155T belonged to the genus Frigoribacterium and was closely related to Frigoribacteriumendophyticum EGI 6500707T (99.4 %), Frigoribacteriumfaeni 801T (98.6 %) and Frigoribacteriummesophilum MSL-08T (96.2 %). The DNA-DNA hybridization values between strain LAM9155T and F. endophyticum JCM 30093T and between strain LAM9155T and F. faeni DSM 10309T were 40.2+/-2.1 and 32.8+/-1.6 %, respectively. The major fatty acids of LAM9155T were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The cell-wall analysis showed the B-type peptidoglycan containing alanine, glutamate, glycine, serine and lysine and that the cell wall contained the sugars galactose and ribose. The genomic DNA G+C content of strain LAM9155T was 68.2 mol%. The predominant menaquinone was MK-9. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, one unknown glycolipid and four unknown lipids. Based on the DNA-DNA hybridization and phenotypic, phylogenetic and chemotaxonomic properties, strain LAM9155T could be distinguished from the recognized species of the genus Frigoribacterium and was suggested to represent a novel species, for which the name Frigoribacterium salinisoli sp. nov. is proposed. The type strain is LAM9155T (=ACCC 19902T=JCM 30848T). Moreover, the transfer of F. mesophilum Dastager et al. 2008 to Parafrigoribacterium gen. nov. as Parafrigoribacterium mesophilum comb. nov. (type strain MSL-08T=DSM 19442T=KCTC 19311T) is also proposed. PMID- 27654624 TI - Vasculogenesis and Its Cellular Therapeutic Applications. AB - Vasculogenesis was originally defined by Risau in 1997 [Nature 386: 671-674] as the de novo formation of vessels from endothelial progenitor cells (EPCs), so called angioblasts. Initially, this process was believed to be related only to embryonic life; however, further studies reported vasculogenesis to occur also in adult tissues. This overview presents the current knowledge about the origin, differentiation and significance of EPCs that have been observed in various diseases, tumors, and reparative processes. We also summarize the knowledge of how to activate these cells for therapeutic purposes and the outcomes of the therapies. PMID- 27654625 TI - Chronic Subthreshold Cortical Stimulation to Treat Focal Epilepsy. PMID- 27654626 TI - The videolaryngoscopes are now the first choice to see around the corner. PMID- 27654627 TI - Long-term skeletodental stability of mandibular symphyseal distraction osteogenesis: Tooth-borne vs hybrid distraction appliances. AB - OBJECTIVE: To evaluate and compare the long-term skeletodental stability of mandibular symphyseal distraction osteogenesis (MSDO) achieved with the use of tooth-borne vs. hybrid distraction appliances. MATERIALS AND METHODS: Posttreatment and follow-up orthodontic records were collected for 33 patients. The 14 patients who underwent distraction with a tooth-borne appliance had a mean follow-up of 5.08 years. The 19 patients who underwent distraction with a hybrid appliance had a mean follow-up of 6.07 years. Records included intraoral photographs, study models, postero-anterior cephalometric radiographs, and lateral cephalometric radiographs. Total changes of 16 measurements were analyzed to compare patients who underwent the tooth-borne vs. the hybrid distraction. RESULTS: Both groups shared several similar and significant (P < .05) changes from posttreatment to follow-up records. Cast analysis showed a decrease in intercanine width and arch length and an increase in irregularity index. The postero-anterior cephalometric radiograph showed an increase in the width of the interincisal apices. The lateral cephalometric radiograph showed a decrease in the MP-L1 angle. The only statistically significant difference between the two appliances was the intercentral incisor contact point. CONCLUSION: Changes found are consistent with those found in untreated and orthodontically treated individuals over time. The long-term changes in the current patient sample can be determined to be expected and acceptable. MSDO is a viable treatment option with the use of either a hybrid or tooth-borne appliance. PMID- 27654628 TI - Predictors of postretention stability of mandibular dental arch dimensions in patients treated with a lip bumper during mixed dentition followed by fixed appliances. AB - OBJECTIVE: To identify which dental and/or cephalometric variables were predictors of postretention mandibular dental arch stability in patients who underwent treatment with transpalatal arch and lip bumper during mixed dentition followed by full fixed appliances in the permanent dentition. MATERIALS AND METHODS: Thirty-one patients were divided into stable and relapse groups based on the postretention presence or absence of relapse. Intercuspid, interpremolar, and intermolar widths; arch length and perimeter; crowding; and lower incisor proclination were evaluated before treatment (T0), after lip bumper treatment (T1), after fixed appliance treatment (T2), and a minimum of 3 years after removal of the full fixed appliance (T3). Logistic regression analyses were performed to evaluate the effect of changes between T0 and T1, as predictive variables, on the occurrence of relapse at T3. RESULTS: The model explained 53.5 % of the variance in treatment stability and correctly classified 80.6 % of the sample. Of the seven prediction variables, intermolar and interpremolar changes between T0 and T1 (P = .024 and P = .034, respectively) were statistically significant. For every millimeter of increase in intermolar and interpremolar widths there was a 1.52 and 2.70 times increase, respectively, in the odds of having stability. There was also weak evidence for the effect of sex (P = .047). CONCLUSIONS: The best predictors of an average 4-year postretention mandibular dental arch stability after treatment with a lip bumper followed by full fixed appliances were intermolar and interpremolar width increases during lip bumper therapy. The amount of relapse in this crowding could be considered clinically irrelevant. PMID- 27654629 TI - Gifts from orthodontists to general dentists. AB - OBJECTIVES: To determine how often general dentists receive gifts from orthodontists, the value and number of the gifts they receive, and how they perceive the motivation behind the gift. MATERIALS AND METHODS: This was a questionnaire-based study. A questionnaire was constructed and tested for validity and reliability. An electronic version of survey was sent via email to 1300 general dentists. RESULTS: The validity and reliability of the survey was confirmed. Two hundred fifty-four valid responses were received (20%). Eighty five percent of responding general practitioners reported that they received gifts from an orthodontist. Almost 100% reported that they referred patients to orthodontists. About one-third of the responding general practitioners reported that their office provided orthodontic care. There were statistically significant correlations between the number of annual patient referrals the general practitioners reported making and the number and value of the gifts they received from the orthodontists. Female general practitioners reported receiving a higher number of gifts of greater total value than male practitioners. General practitioners who reported providing orthodontic treatment did not differ from those who did not in the number of referrals they made annually and the number and value of the gifts they received. Quality of care was the most common reason general practitioners reported for their referral to an orthodontist. Forty-four percent of the responders reported that they received discounted orthodontic treatment. CONCLUSIONS: General practitioners refer patients to orthodontists and receive gifts from them. The number and value of the gifts reflects the number of referrals they make. PMID- 27654630 TI - Intracellular Hg(0) Oxidation in Desulfovibrio desulfuricans ND132. AB - The disposal of elemental mercury (Hg(0)) wastes in mining and manufacturing areas has caused serious soil and groundwater contamination issues. Under anoxic conditions, certain anaerobic bacteria can oxidize dissolved elemental mercury and convert the oxidized Hg to neurotoxic methylmercury. In this study, we conducted experiments with the Hg-methylating bacterium Desulfovibrio desulfuricans ND132 to elucidate the role of cellular thiols in anaerobic Hg(0) oxidation. The concentrations of cell-surface and intracellular thiols were measured, and specific fractions of D. desulfuricans ND132 were examined for Hg(0) oxidation activity and analyzed with extended X-ray absorption fine structure (EXAFS) spectroscopy. The experimental data indicate that intracellular thiol concentrations are approximately six times higher than those of the cell wall. Cells reacted with a thiol-blocking reagent were severely impaired in Hg(0) oxidation activity. Spheroplasts lacking cell walls rapidly oxidized Hg(0) to Hg(II), while cell wall fragments exhibited low reactivity toward Hg(0). EXAFS analysis of spheroplast samples revealed that multiple different forms of Hg thiols are produced by the Hg(0) oxidation reaction and that the local coordination environment of the oxidized Hg changes with reaction time. The results of this study indicate that Hg(0) oxidation in D. desulfuricans ND132 is an intracellular process that occurs by reaction with thiol-containing molecules. PMID- 27654631 TI - Photoinduced Homolytic Bond Cleavage of the Central Si-C Bond in Porphyrin Macrocycles Is a Charge Polarization Driven Process. AB - Photoinduced cleavage of the bond between the central Si atom in porphyrin macrocycles and the neighboring carbon atom of an axial alkyl ligand is investigated by both experimental and computational tools. Photolysis and electron paramagnetic resonance measurements indicate that the Si-C bond cleavage of Si-phthalocyanine occurs through a homolytic process. The homolytic process follows a low-lying electronic excitation of about 1.8 eV that destabilizes the carbide bond of similar bond dissociation energy. Using electronic structure calculations, we provide insight into the nature of the excited state and the resulting photocleavage mechanism. We explain this process by finding that the electronic excited state is of a charge transfer character from the axial ligand toward the macrocycle in the reverse direction of the ground state polarization. We find that the homolytic process yielding the radical intermediate is energetically the most stable mechanistic route. Furthermore, we demonstrate using our computational approach that changing the phthalocyanine to smaller ring system enhances the homolytic photocleavage of the Si-C bond by reducing the energetic barrier in the relevant excited states. PMID- 27654632 TI - Major Greenwood (1880-1949): the biography. AB - Background is provided on the discovery of an unpublished biography of Major Greenwood written by one of his sons. The motivation and preparation for online publication of the biography in Statistics in Medicine are outlined. (c) 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID- 27654633 TI - MOF-Derived Flower-like MoS2@TiO2 Nanohybrids with Enhanced Activity for Hydrogen Evolution. AB - A simple hydrothermal method is developed for synthesizing crystalline MoS2@TiO2 nanohybrids with metal-organic framework (MOF) as precursor. At an optimal ratio of 14.6 wt % MoS2, the resultant material exhibits prominent catalytic activity for hydrogen evolution reaction (HER) with a high hydrogen production rate of 10 046 MUmol h-1 g-1 under visible light illumination with fluorescein as photosensitizer. Furthermore, the synthesized catalyst also possesses an attractive electrocatalytic activity with an onset overpotential of -300 mV (vs RHE) and a Tafel slope of ~81 mV dec-1. The enhanced catalyst performances are mainly attributed to the in situ formed active sites, featuring a uniform dispersion and strong connection of MoS2 and TiO2, which can facilitate electron transfer. In addition, the MoS2@TiO2 nanohybrids are highly stable and completely recyclable over HER. PMID- 27654634 TI - Finding the Way to Solar Fuels with Dye-Sensitized Photoelectrosynthesis Cells. AB - The dye-sensitized photoelectrosynthesis cell (DSPEC) integrates high bandgap, nanoparticle oxide semiconductors with the light-absorbing and catalytic properties of designed chromophore-catalyst assemblies. The goals are photoelectrochemical water splitting into hydrogen and oxygen and reduction of CO2 by water to give oxygen and carbon-based fuels. Solar-driven water oxidation occurs at a photoanode and water or CO2 reduction at a cathode or photocathode initiated by molecular-level light absorption. Light absorption is followed by electron or hole injection, catalyst activation, and catalytic water oxidation or water/CO2 reduction. The DSPEC is of recent origin but significant progress has been made. It has the potential to play an important role in our energy future. PMID- 27654635 TI - Early Father Involvement and Subsequent Child Behaviour at Ages 3, 5 and 7 Years: Prospective Analysis of the UK Millennium Cohort Study. AB - OBJECTIVE: Fathers are increasingly involved in care of their babies and young children. We assessed the association of resident fathers' involvement with subsequent behaviour of their children, examining boys and girls separately. METHODS: We used longitudinal data from the UK Millennium Cohort Study for children born in 2000-2001, divided into three separate analysis periods: ages 9 months to 3 years, 3 to 5 years, and 5 to 7 years. By exploratory factor analysis of self-reported attitudes and engagement in caring activities, we derived composite measures of various types of father involvement at 9 months, 3 and 5 years. Where possible we created equivalent measures of mother involvement. Child behaviour was assessed by the Strengths and Difficulties Questionnaire (SDQ), which was completed by the mother when the child was aged 3, 5 and 7 years. We estimated gender-specific odds ratios for behaviour problems per quintile of father involvement, using separate logistic regression models for boys and girls in each analysis period. We controlled for a wide range of potential confounders: characteristics of the child (temperament and development at 9 months, and illness and exact age at outcome), equivalent mother involvement where appropriate, and factors related to socioeconomic status, household change, and parental well-being, where statistically significant. RESULTS: Paternal positive parenting beliefs at age 9 months and increased frequency of creative play at age 5 years were significantly associated with lower risk of subsequent behaviour problems (SDQ total difficulties) in both boys and girls (p<0.05), odds ratios ranging between 0.81 and 0.89 per quintile of involvement. No associations were observed for other composite measures of caring activity by the father at 9 months, 3 years or 5 years. CONCLUSION: Quality of parenting, rather than the division of routine care between parents, was associated with child behavioural outcomes. PMID- 27654636 TI - Fatal Clostridium perfringens Septicemia After Colonoscopic Polypectomy, Without Bowel Perforation. AB - Since its introduction, colonoscopy has played an important role as a diagnostic, therapeutic, and screening tool. In general, colonoscopy is regarded as a safe procedure, but complications may occur. The most dreaded of these complications is colonic perforation. Bacteremia postprocedure may occur, and although it is not uncommon, it rarely results in clinically significant complications. Patients with IBD (inflammatory bowel disease) are a high-risk population for bacteremia, which may leads to bowel wall overstepping by the bacteria. With regard to that, we report a fatal case of gas gangrene complicating colonoscopy polypectomy without bowel perforation in a healthy adult. To the best of our knowledge, only two other cases of retroperitoneal gas gangrene associated with colonoscopy polypectomy without bowel perforation have been described in international literature, but none of which was completed by a molecular biology analysis. PMID- 27654637 TI - What are People's Experiences of a Novel Cognitive Behavioural Therapy for Bipolar Disorders? A Qualitative Investigation with Participants on the TEAMS Trial. AB - : Background Psychological interventions for bipolar disorders typically produce mixed outcomes and modest effects. The need for a more effective intervention prompted the development of a new cognitive behavioural therapy, based on an integrative cognitive model ('Think Effectively About Mood Swings' [TEAMS] therapy). Unlike previous interventions, TEAMS addresses current symptoms and comorbidities, and helps clients achieve long-term goals. A pilot randomized controlled trial (the TEAMS trial) of the therapy has recently concluded. This study explored participants' experiences of TEAMS, recommendations for improvement and experiences of useful changes post-therapy. Methods Fourteen TEAMS therapy participants took part in semi-structured interviews. Their accounts were analysed using interpretative thematic analysis. Two researchers coded the dataset independently. Member checks were conducted of the preliminary themes. Results Two overarching themes; 'useful elements of therapy' and 'changes from therapy' encompassed 12 emerging subthemes. Participants appreciated having opportunities to talk and described the therapy as person-centred and delivered by caring, approachable and skilled therapists. Some recommended more sessions than the 16 provided. Helpful therapeutic techniques were reported to be, normalization about moods, methods to increase understanding of moods, relapse prevention, reappraisal techniques and metaphors. However, some did not find therapeutic techniques helpful. Post-therapy, many reported changes in managing mood swings more effectively and in their thinking (although some participants reported changes in neither). Many described increased acceptance of themselves and of having bipolar disorder, increased productivity and reduced anxiety in social situations. Conclusions The present study evaluates participants' therapy experiences in detail, including aspects of therapy viewed as helpful, and meaningful post-therapy outcomes. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: This is the first paper to qualitatively explore people's experiences of individual psychotherapy for bipolar disorders. It highlights elements of psychotherapy described as particularly helpful or unhelpful and the clinical changes viewed as most impactful. Participants reported benefitting in a number of ways from TEAMS therapy. They valued learning to reappraise and problem solve situations and manage moods. Participants identified TEAMS techniques as helpful, such as exploring advantages and disadvantages of moods, and building healthy self-states. PMID- 27654638 TI - Effect of obesity on sperm retrieval outcome and reproductive hormone levels in Japanese azoospermic men with and without Klinefelter syndrome. AB - Obesity is reported to have adverse effects on semen quality and the endocrine system. In this study, we evaluated the effect of obesity on sperm retrieval outcome and reproductive hormone levels in Japanese men with non-obstructive azoospermia (NOA). This study is based on the clinical records of 217 men [172 with a 46,XY karyotype, 45 with Klinefelter syndrome (KS)] with NOA who underwent microdissection testicular sperm extraction at Nagoya City University Hospital between January 2004 and December 2014. Body mass index (BMI) and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone (TT) were measured in all patients. In a subset of patients, bioavailable testosterone (cBAT) also was calculated. Values were evaluated separately in patients with and without KS. Sperm retrieval rates (SRRs) in 46,XY men with a BMI <25 kg/m2 and >=25 kg/m2 were 29.3% and 18.4%, respectively (p = 0.142), while SRRs in KS men with a BMI <25 kg/m2 and >=25 kg/m2 were 25.0% and 35.3%, respectively (p = 0.460). TT level in men with a BMI >=25 kg/m2 was lower than that in men with a BMI <25 kg/m2 , regardless of KS status. According to Pearson product-moment correlation coefficients, TT and cBAT levels tended to have negative correlations with BMI; however, statistical significance was observed only for TT level in 46,XY men (r = 0.340, p < 0.001). LH and FSH levels were negatively correlated with BMI in KS men (r = -0.466, p = 0.001 and r = 0.647, p < 0.001, respectively), but not in 46,XY men. These results suggest that obesity may be irrelevant to sperm retrieval outcome in patients with NOA. The negative correlations between gonadotropins and BMI in patients with KS suggest an underlying suppressive effect on gonadotropin excretion, which is distinctive in obese patients with KS. PMID- 27654640 TI - Expressions of urothelial functional proteins in idiopathic detrusor overactivity patients refractory to antimuscarinic therapy with different urodynamic characteristics. AB - AIMS: This study investigated the expressions of PGP9.5, P2 X 3 , muscarinic receptor (M3) and beta-3 adrenoreceptor (AR) in idiopathic detrusor overactivity (IDO) patients refractory to antimuscarinic treatment, and analyzed the correlation between protein expressions and clinical symptoms of IDO bladders with different urodynamic characteristics. METHODS: Specimens of 48 IDO and 10 control patients without lower urinary tract symptoms were included. The levels of these proteins from bladder mucosa were determined by Western blotting. RESULTS: The expression levels of beta3-AR and M3 receptor were similar between IDO patients and controls. When IDO patients were divided into two subgroups, phasic DO and terminal DO, the results showed that beta3-AR level in the patients with phasic DO was significantly higher than that of the controls and terminal DO (Both P < 0.05). PGP9.5 and P2 X 3 levels were also significantly increased in phasic DO subgroup than controls. P2 X 3 receptor was positively correlated with PGP9.5 and beta3-AR, and negatively correlated with the first sensation of bladder filling and voided volume in phasic DO. CONCLUSIONS: Similar expression M3 receptor and increased P2 X 3 levels in phasic DO, compared with the controls, indicate that dysregulation of purinergic bladder signaling may contribute to the pathogenesis of phasic DO refractory to antimuscarinics. Elevated expression of beta3-AR in phasic DO but not in terminal DO patients may explain the different urodynamic characteristics of DO between the two subgroups. Our findings suggest that beta3-AR agonist or P2 X 3 antagonist might be a good treatment choice for patients with phasic DO refractory to antimuscarinic therapy. PMID- 27654639 TI - Versatile Nanodelivery Platform to Maximize siRNA Combination Therapy. AB - The unsatisfactory outcomes of typical multiple cytotoxic chemotherapeutic combination therapies used to treat patients have fostered a need for new unconventional combinations of therapeutic agents. Among the candidates, siRNA has been widely discussed and tested. However, the right time right place codelivery of siRNA with other types of active ingredients is challenging because of the possible differences among their physiochemical and pharmacodynamics properties. To accomplish a synergistic cytotoxic effect, a nanoassembly is thus designed to codeliver siRNA with other therapeutic agents. A siRNA, targeting prosurvival gene for the p75 neurotrophin receptor, and an organelle-fusing peptide, targeting mitochondria, are layered onto a nanotemplate by charge-charge interaction, followed by a layer of CD44 targeting ligand. The formulated triple functional nanomedicine is efficiently internalized by the CD44 expressing triple negative breast cancer cells. The encapsulated siRNA and the pro-apoptotic peptide are released inside cells, silencing the intended prosurvival gene, and inducing apoptosis by fusing the mitochondrial membrane, respectively. A synergistic effect is achieved by this three-agent combination. The design of the developed multifunctional nanomedicine can be generalized to deliver other siRNA and drugs for a maximum therapeutic combination with minimal off-targeting effects. PMID- 27654641 TI - Inhibition of soluble guanylyl cyclase by small molecules targeting the catalytic domain. AB - Soluble guanylyl cyclase (sGC) plays a crucial role in cyclic nucleotide signaling that regulates numerous important physiological processes. To identify new sGC inhibitors that may prevent the formation of the active catalytic domain conformation, we carried out an in silico docking screen targeting a 'backside pocket' of the inactive sGC catalytic domain structure. Compounds 1 and 2 were discovered to inhibit sGC even at high/saturating nitric oxide concentrations. Both compounds also inhibit the BAY 58-2667-activated sGC as well as BAY 41-2272 stimulated sGC activity. Additional biochemical analyses showed that compound 2 also inhibits the isolated catalytic domain, thus demonstrating functional binding to this domain. Both compounds have micromolar affinity for sGC and are potential leads to develop more potent sGC inhibitors. PMID- 27654643 TI - Children macular thickness correlated with mother macular thickness. PMID- 27654642 TI - Copper-Catalyzed Amidation of Primary and Secondary Alkyl Boronic Esters. AB - The oxidative copper-catalyzed cross-coupling of functionalized alkyl boronic esters with primary amides is reported. Through the identification of appropriate diketimine ligands, conditions for efficient coupling of both primary and secondary alkyl boronic esters with diverse primary amides, including acetamide, have been developed. PMID- 27654646 TI - A Survey on Visual Approaches for Analyzing Scientific Literature and Patents. AB - The increasingly large number of available writings describing technical and scientific progress, calls for advanced analytic tools for their efficient analysis. This is true for many application scenarios in science and industry and for different types of writings, comprising patents and scientific articles. Despite important differences between patents and scientific articles, both have a variety of common characteristics that lead to similar search and analysis tasks. However, the analysis and visualization of these documents is not a trivial task due to the complexity of the documents as well as the large number of possible relations between their multivariate attributes. In this survey, we review interactive analysis and visualization approaches of patents and scientific articles, ranging from exploration tools to sophisticated mining methods. In a bottom-up approach, we categorize them according to two aspects: (a) data type (text, citations, authors, metadata, and combinations thereof), and (b) task (finding and comparing single entities, seeking elementary relations, finding complex patterns, and in particular temporal patterns, and investigating connections between multiple behaviours). Finally, we identify challenges and research directions in this area that ask for future investigations. PMID- 27654647 TI - Causal relationship and confounding in statistical models. PMID- 27654648 TI - Randomized clinical trial of chewing gum after laparoscopic colorectal resection. AB - BACKGROUND: Chewing gum may enhance intestinal motility after surgery. This trial studied whether chewing gum could lead to a further reduction in ileus in patients who had a laparoscopic colorectal resection and followed an enhanced recovery programme. METHODS: Patients undergoing laparoscopic colorectal resection were randomized to a control or intervention group. Patients in the control group received a standardized recovery programme. Patients in the intervention group were, in addition, given chewing gum three times daily from day 1 until discharge. Primary outcome measures were time to first flatus and first bowel motion. Time to feeling hungry and hospital stay were secondary outcome measures. RESULTS: Forty-one patients were randomized into each group. Thirty-seven patients underwent rectal resection and 45 had a colonic resection. Time to passage of flatus was shorter (18 versus 34 h; P = 0.007), first bowel motion occurred earlier (19 versus 44 h; P = 0.001) and time to feeling hungry was earlier (16 versus 25 h; P = 0.001) in the intervention group. There was no difference in the duration of hospital stay (5 days in the intervention group versus 5.5 days in the control group). Subgroup analyses revealed that the benefits of chewing gum were clearer in patients who had a colonic resection, with a shorter time to first flatus (20 versus 35 h; P = 0.043), first bowel motion (19 versus 53 h; P = 0.014) and feeling hungry (14 versus 40 h; P = 0.001). No adverse events were attributed to chewing gum. CONCLUSION: Chewing gum is a simple intervention that speeds intestinal transit in patients managed with a recovery programme after laparoscopic colorectal resection. REGISTRATION NUMBER: NCT02419586 (https://clinicaltrials.gov/). PMID- 27654651 TI - Correction: Molecular profiling of cetuximab and bevacizumab treatment of colorectal tumours reveals perturbations in metabolic and hypoxic response pathways. PMID- 27654653 TI - Five minutes with . . . Caroline Gannon. PMID- 27654652 TI - Uni-Directional Transportation on Peristome-Mimetic Surfaces for Completely Wetting Liquids. AB - Liquid uni-directional transport on solid surface without energy input would advance a variety of applications, such as in bio-fluidic devices, self lubrication, and high-resolution printing. Inspired by the liquid uni-directional transportation on the peristome surface of Nepenthes alata, here, we fabricated a peristome-mimicking surface through high-resolution stereo-lithography and demonstrated the detailed uni-directional transportation mechanism from a micro scaled view visualized through X-ray microscopy. Significantly, an overflow controlled liquid uni-directional transportation mechanism is proposed and demonstrated. Unlike the canonical predictions for completely wetting liquids spreading symmetrically on a high-energy surface, liquids with varied surface tensions and viscosities can spontaneously propagate in a single preferred direction and pin in all others. The fundamental understanding gained from this robust system enabled us to tailor advanced micro-computerized tomography scanning and stereo-lithography fabrication to mimic natural creatures and construct a wide variety of fluidic machines out of traditional materials. PMID- 27654654 TI - Identification of gene knockdown targets conferring enhanced isobutanol and 1 butanol tolerance to Saccharomyces cerevisiae using a tunable RNAi screening approach. AB - Improving yeast tolerance to 1-butanol and isobutanol is a step toward enabling high-titer production. To identify previously unknown genetic targets leading to increased tolerance, we establish a tunable RNA interference (RNAi) screening approach. Specifically, we optimized the efficiency and tunability of RNA interference library screening in yeast, ultimately enabling downregulation efficiencies from 0 to 94 %. Using this system, we identified the Hsp70 family as a key regulator of isobutanol tolerance in a single round of screening, with downregulation of these genes conferring up to 64 % increased growth in 12 g/L isobutanol. For 1-butanol, we find through two rounds of iterative screening that the combined downregulation of alcohol dehydrogenase and enolase improves growth up to 3100 % in 10 g/L 1-butanol. Collectively, this work improves the tunability of RNAi in yeast as demonstrated by the discovery of novel effectors for these complex phenotypes. PMID- 27654655 TI - Detection, production, and application of microbial arylsulfatases. AB - Arylsulfatases are enzymes which catalyze the hydrolysis of arylsulfate ester bonds to release a free sulfonate. They are widespread in nature and are found in microorganisms, most animal and human tissues, and plant seeds. However, this review focuses on arylsulfatases from microbial origin and gives an overview of different assays and substrates used to determine the arylsulfatase activity. Furthermore, the production of microbial arylsulfatases using wild-type organisms as well as the recombinant production using Escherichia coli and Kluyveromyces lactis as expression hosts is discussed. Finally, various potential applications of these enzymes are reviewed. PMID- 27654656 TI - A counterselection method for Lactococcus lactis genome editing based on class IIa bacteriocin sensitivity. AB - In this paper, we present a new counterselection method for deleting fragments from Lactococcus lactis chromosome. The method uses a non-replicating plasmid vector, which integrates into the chromosome and makes the cell sensitive to bacteriocins. The integration vector carries pUC ori functional in Escherichia coli but not in L. lactis, an erythromycin resistance gene for selecting single crossover integrants, and two fragments from L. lactis chromosome for homologous recombinations. In addition, the integration vector is equipped with the Listeria monocytogenes gene mptC encoding the mannose-phosphotransferase system component IIC, the receptor for class IIa bacteriocins. Expression of mptC from the integration vector renders the naturally resistant L. lactis sensitive to class IIa bacteriocins. This sensitivity is then used to select the double crossover colonies on bacteriocin agar. Only the cells which have regained the endogenous bacteriocin resistance through the loss of the mptC plasmid will survive. The colonies carrying the desired deletion can then be distinguished from the wild type revertants by PCR. By using the class IIa bacteriocins leucocin A, leucocin C or pediocin AcH as the counterselective agents, we deleted 22- and 33-kb chromosomal fragments from the wild-type nisin producing L. lactis strain N8. In conclusion, this counterselection method presented here is a convenient, efficient and inexpensive technique to generate successive deletions in L. lactis chromosome. PMID- 27654657 TI - Biotechnological production of enantiomerically pure d-lactic acid. AB - The fermentation process of l-lactic acid is well known. Little importance was attached to d-lactic acid, but in the past 10 years, d-lactic acid gained significantly in importance. d-Lactic acid is an interesting precursor for manufacturing heat-resistant polylactic acid (PLA) bioplastics which can be widely used, for example as packaging material, coatings, for textiles or in the automotive industry.This review provides a comprehensive overview of the most recent developments, including a spectrum of studied microorganisms and their capabilities for the production of d-lactic acid. Additionally, the technological achievements in biotechnological d-lactic acid production including fermentation techniques like fed batch, simultaneous saccharification, and fermentation and continuous techniques are presented. Attention is also turned to suitable alternative substrates and their applicability in fermentation processes. Furthermore, advantages and disadvantages of product recovery and purification are discussed. Economic aspects of PLA are pointed out, and the present industrial producers of lactic acid are briefly introduced. PMID- 27654658 TI - C-arm computed tomography and volume perfusion computed tomography (VPCT)-based assessment of blood volume changes in hepatocellular carcinoma in prediction of midterm tumor response to transarterial chemoembolization: a single center retrospective trial. AB - BACKGROUND: This study aims to evaluate immediate changes in perfusion parameters in hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) in C arm computed tomography (CT) and volume perfusion CT (VPCT) and prediction of midterm tumor response. METHODS: Twenty-five patients (median age 66, range 61 to 75 years) with 62 HCC lesions undergoing TACE received immediate pre- and post interventional assessment by C-arm CT and VPCT. Cross-sectional imaging was analyzed at baseline and approximately 12 weeks after TACE according to modified RECIST criteria. Outcome was defined as objective response (OR, > 30 % reduction of viable tumor) or non-OR. Perfusion parameters were evaluated in C-arm CT [parenchymal blood volume (PBV)] and VPCT [blood volume (BV) and blood flow (BF)]. Ratios of perfusion parameters before and after TACE within the tumor and the non-affected liver parenchyma were calculated. RESULTS: Correlation between tumor PBV and BV revealed a moderate correlation (rho = 0.45, p = 0.005). In non affected liver parenchyma, a significant decrease in PBV was seen, compared to a significant increase in BF and BV. Perfusion ratios in HCC lesions were significantly (p < 0.05) increased in OR group compared to non-OR patients in C arm CT and VPCT: PBV ratio (0.95 (0.06) to 0.67 (0.38), BV ratio 0.63 (0.34) to 0.15 (0.6), and BF ratio 0.6 (0.32) to 0.22 (0.51). Logistic regression including PBV and BF allowed prediction of OR (sensitivity 88 %/specificity of 83 %). CONCLUSIONS: Perfusion parameters acquired by C-arm CT and VPCT cannot simply be substituted by each other, but show similar capability in prediction of midterm tumor response. PMID- 27654659 TI - Current and projected burden of heart failure in the Australian adult population: a substantive but still ill-defined major health issue. AB - BACKGROUND: Comprehensive epidemiological data to describe the burden of heart failure (HF) in Australia remain lacking despite its importance as a major health issue. Herewith, we estimate the current and future burden of HF in Australia using best available data. METHODS: Australian-specific and the most congruent international epidemiological and health utilisation data were applied to the Australian population (adults aged >= 45 years, 8.9 of 22.7 million total population in 2014) on an age and sex-specific basis. We estimated the current incident and prevalent cases of clinically overt/symptomatic HF (predominately those with reduced ejection fraction), hospital activity (diagnosis of HF as a primary or secondary reason for admission) and health care costs in 2014 and future prevalence and burden of HF projected to 2030. RESULTS: We estimated that over 61,000 (6.9 per 1000 person-years) adult Australians aged >= 45 years (58 % women) are diagnosed with HF with clinically overt signs and symptoms every year. On a conservative basis, 480,000 (6.3 %, 95 % CI 2.6 to 10.0 %) Australians (66 % men) are now affected by the syndrome with > 150,000 hospitalisations in excess of 1 million days in hospital per annum. The annual cost of managing HF in the community is approximately $900 million and nearly $2.7 billion ($1.5 versus $1.2 billion, men versus women) when considering the additional cost of in-patient care. We predict that the prevalence and future burden of HF will continue to increase over the next 10-15 years to nearly 750,000 people with an estimated annual health care cost of $3.8 billion. CONCLUSIONS: Australia is not immune to the growing magnitude and implications of a sustained epidemic of HF in an ageing population. However, its public health and economic burden will remain ill defined until more definitive Australian-specific data are generated. PMID- 27654660 TI - Investigating the key indicators for evaluating post-disaster shelter. AB - This study sought to identify the primary indicators for evaluating shelter assistance following natural disasters and then to develop a shelter evaluation instrument based on these indicators. Electronic databases and the 'grey' literature were scoured for publications with a relation to post-disaster shelter assistance. Indicators for evaluating such assistance were extracted from these publications. In total, 1,525 indicators were extracted from 181 publications. A preliminary evaluation instrument was designed from these 1,525 indicators. Shelter experts checked the instrument for face and content validity, and it was revised subsequently based on their input. The revised instrument comprises a version for use by shelter agencies (48 questions that assess 23 indicators) and a version for use by beneficiaries (52 questions that assess 22 indicators). The instrument can serve as a standardised tool to enable groups to gauge whether or not the shelter assistance that they supply meets the needs of disaster-affected populations. PMID- 27654661 TI - The use of anti stretch marks' products by women in pregnancy: a descriptive, cross-sectional survey. AB - BACKGROUND: Stretch marks (Striae gravidarum) are a cutaneous change occurring commonly during pregnancy. A variety of products are available and promoted as ways to prevent or reduce their development, but it is not clear what products are used most commonly. The objective of this study was to identify topical products used during pregnancy to prevent or reduce the development of striae gravidarum. We also explored issues around application of the product, cost incurred and influences on women's decisions to use a product. METHODS: In this cross sectional, descriptive survey we collected data from 773 women, via a paper (n = 707) or online (n = 66) questionnaire. Due to missing data in the online survey, 753 women at 36 weeks gestation or more were included in the analyses. Descriptive and inferential statistical analyses were undertaken. RESULTS: Most respondents (n = 589, 78.2 %) indicated that they used a product to prevent or reduce the development of stretch marks during their current pregnancy. A large range of products were used and more than one third of women (n = 210, 36.5 %) had used two or more products. Bio-oil was the most frequently used product (n = 351, 60.9 %) and it was also the most frequently used product among women who used only one product (n = 189, 32.8 %). CONCLUSIONS: Many women apply one of the many products available to prevent or reduce the development of striae gravidarum. Bio-oil was the most commonly used product identified in this study. There is a need for high-quality evidence on the effectiveness of Bio-oil and other products. PMID- 27654662 TI - Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues. AB - Drug-reward cues trigger motivational circuitry, a response linked to drug seeking in animals and in humans. Adverse life events have been reported to increase sensitivity to drug rewards and to bolster drug reward signaling. Therefore, we hypothesized that cocaine-dependent individuals with prior emotional, physical and sexual abuse might have a heightened mesolimbic brain response to cues for drug reward in a new brief-cue probe. Cocaine-dependent human individuals (N = 68) were stabilized in an inpatient setting and then completed an event-related blood-oxygen-level dependent functional magnetic resonance imaging task featuring 500-ms evocative (cocaine, sexual, aversive) and comparator (neutral) cues. Responses to three questions about emotional, physical and sexual abuse from the Addiction Severity Index were used to divide the patients into subgroups (history of Abuse [n = 40] versus No Abuse [n = 28]). When subjects were grouped by the historical presence or absence of emotional, physical or sexual abuse, the Abuse group showed a heightened midbrain, thalamic, caudate, and caudal orbitofrontal cortex response to cocaine cues; a similar result was found in other evocative cues, as well. These findings are the first reported for a 500-ms cocaine-cue probe, and they highlight the ability of very brief evocative cues to activate the brain's motivational circuitry. Although all participants had severe cocaine use disorders, individuals reporting prior abuse had a heightened mesolimbic response to evocative cues. To our knowledge, this is the first study in humans linking a history of abuse to a brain vulnerability (heightened mesolimbic response to drug cues) previously shown to contribute to drug-seeking. PMID- 27654663 TI - Detection of Thrombosis in the Extracorporeal Membrane Oxygenation Circuit by Infrasound: Proof of Concept. AB - As of today, there exist no reliable, objective methods for early detection of thrombi in the extracorporeal membrane oxygenators (ECMO) system. Within the ECMO system, thrombi are not always fixed to a certain component or location in the circuit. Thus, clot fragments of different shapes and consistencies may circulate and give rise to vibrations and sound generation. By bedside sound measurements and additional laboratory experiments (although not detailed herein), we found that the presence of particles (clots or aggregates and fragments of clots) can be detected by analyzing the strength of infra-sound (< 20 Hz) modes of the spectrum near the inlet and outlet of the centrifugal pump in the ECMO circuit. For the few patients that were considered in this study, no clear false positive or negative examples were found when comparing the spectral approach with clinical observations. A laboratory setup provided insight to the flow in and out of the pump, confirming that in the presence of particles a low-amplitude low frequency signal is strongly amplified, enabling the identification of a clot. PMID- 27654664 TI - Dexmedetomidine does not interfere with meta-iodobenzylguanidine (MIBG) uptake at clinically relevant concentrations. AB - BACKGROUND: Neuroblastoma is a pediatric malignancy, and most tumor cells express the norepinephrine transporter (NET) enabling uptake of NET ligands. Meta iodobenzylguanidine (MIBG) is a NET-specific ligand used as a highly specific imaging agent and targeted radiotherapeutic. Patients with neuroblastoma frequently require sedation during targeted radiotherapy. Dexmedetomidine has been increasingly used to achieve efficacious sedation. There are theoretical concerns that this highly selective alpha-2 adrenergic receptor agonist may interfere with active uptake of MIBG through the NET transporter. In this study, we analyzed the impact of [125-iodine]-labeled MIBG ([125 I]MIBG) uptake in the presence of dexmedetomidine in human neuroblastoma-derived cellular models. PROCEDURE: Carrier-free [125 I]MIBG was synthesized using UltraTrace(r) resin (Molecular Insight Pharmaceuticals, Inc., Tarrytown, NY) through radioiododestannylation from a tin precursor bound by a solid-state polymer. NET (SLC6A2) protein expression was determined in human neuroblastoma cell lines (BE2C, SKNSH and IMR5). [125 I]MIBG internalization studies were performed using [125 I]MIBG alone or in combination with either desipramine or dexmedetomidine. Dexmedetomidine and desipramine competitive inhibition studies were performed and concentration at 50% maximal inhibition was calculated. Finally, NET inhibitor dissociation studies were performed in which after pre-incubation with either desipramine or dexmedetomidine, cells were washed and [125 I]MIBG was added. RESULTS: We show dose-dependent inhibition of [125 I]MIBG uptake by dexmedetomidine, but at several logs lower potency than the known NET inhibitor desipramine. A review of pediatric dexmedetomidine pharmacokinetic data shows that the concentrations achieved in the serum are much lower than those required to block MIBG uptake. CONCLUSION: We conclude that dexmedetomidine will not interfere with therapeutic [131 I]MIBG efficacy. PMID- 27654665 TI - Lessons from iatrogenic Cushing syndrome in children. PMID- 27654666 TI - Molecular epidemiology of the enteroviruses associated with hand, foot and mouth disease/herpangina in Dongguan, China, 2015. AB - Enteroviruses (EVs) are the etiological agents involved in most cases of hand, foot and mouth disease (HFMD) and herpangina (HA). Information on the epidemiology profiles of EVs in China is very limited, as the present surveillance system of China focuses on CAV16 and EV71, and no published data are available in Dongguan. The aim of this study is to determine the prevalence of EVs among patients with HFMD and HA in Dongguan, China, during 2015. A total of 271 clinical stool specimens that were clinically determined to be positive for enteroviruses were genotyped by semi-nested polymerase chain reaction (PCR) for the VP1 genes of EVs. The results showed that a total of 14 enterovirus genotypes were identified among HFMD and HA patients in this study. CVA6 was the most common genotype for HFMD, and CVA2 accounted for the majority of HA cases in this study. Sequence and phylogenetic analysis showed that all of the CVA6 and CVA2 strains identified in our study displayed a close genetic relationship to strains identified in other cities in China. This study also demonstrates that there are associations between particular causative enterovirus genotypes and some clinical symptoms, which may provide useful information for improving case prevention, diagnosis and treatment of HFMD and HA. PMID- 27654667 TI - Rescue of avian leukosis subgroup-J-associated acutely transforming viruses carrying different lengths of the v-fps oncogene and analysis of their tumorigenicity. AB - In our previous study, six subgroup J strains of avian leukosis virus (ALV-J) associated acutely transforming viruses carrying different lengths of the v-fps oncogene, designated as Fu-J and Fu-J1-5, were isolated and characterized from fibrosarcomas in ALV-J-infected chickens. In the present study, the oncogenic potential of Fu-J and Fu-J1-5 was investigated using a reverse genetics technique. Six replication-defective viruses, named rFu-J and rFu-J1-5, were rescued with the replication-competent rescued ALV-J strain rSDAU1005 as a helper virus by co-transfection of chicken embryo fibroblast monolayers with infectious clone plasmids. Experimental bird studies were performed, demonstrating that only the rescued rFu-J virus carrying the complete v-fps oncogene with rSDAU1005 as the helper virus could induce acute fibrosarcoma after inoculation in specific pathogen-free (SPF) chickens. These results provide direct evidence that the replication-defective acutely transforming Fu-J virus, with the complete v-fps oncogene, was associated with acute fibrosarcoma in chickens infected with ALV-J in the field, as reported previously. PMID- 27654668 TI - Biological and molecular characterization of a tomato isolate of potato virus Y (PVY) of the PVYC lineage. AB - An isolate of potato virus Y (PVY), PVY-H14, was collected on the island of Oahu, Hawaii, from tomato plants exhibiting stunting and necrotic lesions on leaves. PVY-H14 triggered the hypersensitive resistance response in potato cultivars King Edward and Maris Bard, typical of a PVYC strain, and was unable to infect systemically the four tested cultivars, Desiree, Maris Bard, King Edward, and Russet Norkotah. Phylogenetic analysis of H14 and the whole genomes of 31 PVY isolates of non-recombinant strains of PVY placed PVY-H14 in the same clade with PVYC and several unclassified PVY isolates from tomato and tobacco. PMID- 27654670 TI - 4th International Conference on Ambulatory Monitoring of Physical Activity and Movement (Limerick, Ireland, 10-12 June 2015). PMID- 27654669 TI - The molecular epidemiology of bovine rotaviruses circulating in Iran: a two-year study. AB - Bovine group A rotavirus (bovine RVA) is recognized as a major cause of severe gastroenteritis in newborn calves. The purpose of this study was to estimate the prevalence and identify the genotypes of circulating bovine RVA in newborn diarrheic calves. Two hundred fifty-three stool samples of diarrheic calves up to 1 month old were collected from 42 industrial dairy farms in two Iranian provinces during March 2010 to February 2012. All collected samples were screened for the presence of bovine RVA by RT-PCR, and the G and P genotypes were determined by semi-nested multiplex RT-PCR assay. The results of RT-PCR indicated that 49.4 % (125 out of 253) of the samples were positive for bovine RVA. The G and P genotyping of a subset of positive samples (n = 85) by semi-nested multiplex RT-PCR revealed that G6 (55.3 %) and G10 (43.5 %) and P[5] (51.8 %) and P[11] (27 %) were the most prevalent G and P genotypes, respectively. G6P[5] was the dominant genotype (35.3 %), followed by G10P[5], G10P[11] and G6P[11], with prevalence rates of 16.5 %, 15.3 % and 10.6 %, respectively. Sequence analysis of 20 VP7 and four VP4 genes showed highest nucleotide sequence identity with the corresponding genes of strains RVA/Cow-tc/GBR/UK/1973/G6P7[5] and RVA/Cow tc/USA/B223/XXXX/G10P[11]. The results of this study reveal the diversity of G and P genotypes in bovine RVA samples from diarrheic Iranian calves and expands our knowledge of bovine RVA infections in the Middle East. These results also highlight the importance of producing of an effective rotavirus vaccine and its inclusion in the national cattle immunization program. PMID- 27654679 TI - Response to Protocol Review Scenario: More oversight and communication might be needed. PMID- 27654680 TI - How should an IACUC handle high mortality rates? PMID- 27654681 TI - Response to Protocol Review Scenario: Postapproval monitoring could have identified problems earlier. PMID- 27654682 TI - Response to Protocol Review Scenario: Adverse events and deficiencies. PMID- 27654683 TI - Response to Protocol Review Scenario: A Word from OLAW. PMID- 27654684 TI - Brain-machine interfaces: assistive, thought-controlled devices. PMID- 27654685 TI - On strength training paradigms for rodents. PMID- 27654686 TI - Simple blood typing and cross matching techniques in swine. PMID- 27654687 TI - Keeping current with regulations and requirements. PMID- 27654688 TI - Evaluation of buprenorphine hydrochloride Pluronic((r)) gel formulation in male C57BL/6NCrl mice. AB - Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic((r)) F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. PMID- 27654689 TI - A comparison of sexing methods in fetal mice. AB - Accurate mouse sexing is vital when conducting research examining sexual dimorphisms. Late fetal and newborn mouse pups are more immature than many previously described sexing methods allow. This study compares the sexing accuracy of a newly described internal gonad sexing method to a recently described peritoneal pigmentation sexing method in embryonic day 20 C57BL/6J mouse pups, using Sry genotyping to confirm the sex. The internal gonad sexing method was found to be highly accurate, while the peritoneal pigmentation method was slightly less accurate. Therefore, while Sry genotyping remains the gold standard, immediate and less expensive sexing methods can be performed accurately as early as the late fetal period in C57BL/6J mice. PMID- 27654690 TI - The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia. AB - Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility is also important. Light intensity, isoflurane, and CO2 flow rate were studied for their impact on the stress response of mice during CO2 euthanasia. Behavior was observed and scored during euthanasia and serum corticosterone was measured immediately after death. Unsurprisingly, animals euthanized with a high-flow rate of CO2 became unconscious in the least amount of time, while animals euthanized with a low-flow rate required the most time to reach unconsciousness. There was a significant increase in anxious behaviors in animals in the isoflurane group (F1,12 = 6.67, P = 0.024), the high-flow rate CO2 group (F1,12 = 10.24, P = 0.007), and bright chamber group (F1,12 = 7.27, P = 0.019). Serum corticosterone was highest in the isoflurane group (124.72 +/- 83.98 ng/ml), however there was no significant difference in corticosterone levels observed for the other study variables of light and flow-rate. A darkened chamber and low CO2 flow rates help to decrease stress experienced during CO2 euthanasia, while the use of isoflurane was observed to increase the stress response during euthanasia. PMID- 27654691 TI - Tools for organizing training, part 4. PMID- 27654692 TI - Hold Gimp in your heart, Dr. Collins. PMID- 27654693 TI - Being clear about animal research. PMID- 27654694 TI - A picture paints a thousand words: the value of images and video for understanding animal research. PMID- 27654695 TI - The case for scientists' engagement in animal research policy-making. PMID- 27654697 TI - Using environmental enrichment and nutritional supplementation to improve breeding success in rodents. PMID- 27654698 TI - A Longitudinal Study of Fathers' and Young Children's Depressive Symptoms. AB - Considerable research has examined the effects of maternal depression on children, but few studies have focused on the relation between paternal and child depressive symptoms, particularly during early childhood. Even fewer studies have been longitudinal, leaving open questions about how paternal and child depression covary over time. The present study sought to address this gap by examining the relation between fathers' and children's depressive symptoms over a 3-year period. Participants were 153 preschool children with behavior problems and their parents. Three longitudinal analytic approaches were used to examine how father and child depression change together and predict one another over time. Additional analyses examined whether externalizing problems or maternal depression might account for the associations between fathers' and children's depressive symptoms. Changes in paternal depression significantly predicted changes in father-reported and mother-reported child depressive symptoms. These effects were evident both in year-to-year fluctuations and in linear trajectories across the 3-year period. Cross-lagged analyses suggested that these relations may have been driven by father-effects; paternal depression at one time point predicted child depression at the next time point, but child depression did not significantly predict later paternal depression. We found little evidence that externalizing problems or maternal depression accounted for the relations between fathers' and children's depressive symptoms. Results provide convergent evidence that fathers' depression may play an important role in the development of depressive symptoms in young children and underscore the importance of including fathers in studies of depression in families. PMID- 27654699 TI - Stapled peptides: providing the best of both worlds in drug development. AB - Peptide-based drug discovery has experienced a remarkable resurgence within the past decade due to the emerging class of inhibitors known as stapled peptides. Stapled peptides are therapeutic protein mimetics that have been locked within a specific conformational structure by hydrocarbon stapling. These peptides are highly important in selectively impairing disease-relevant protein-protein interactions and exhibit significant pharmacokinetic advantages over other forms of therapeutics in terms of affinity, specificity, size, synthetic accessibility and resistance to proteolytic degradation. A series of stapled peptides are currently in development, and the potential successes of these peptides, either as single-agent treatments or as combinational treatments with other therapeutic modalities, could potentially change the landscape of protein therapeutic development. Here, we provide examples of successful discovery efforts to illustrate the research strategies of stapled peptides in drug design and development. PMID- 27654700 TI - Dexmedetomidine sedation reduces atrial fibrillation after cardiac surgery compared to propofol: a randomized controlled trial. AB - BACKGROUND: Atrial fibrillation occurs frequently in patients following cardiac surgery and can be a cause of increased morbidity and mortality. The use of dexmedetomidine to prevent atrial fibrillation is unclear. The present study was designed to evaluate the effect of dexmedetomidine sedation on the incidence of atrial fibrillation after cardiac surgery. METHODS: Upon arrival to the intensive care unit (ICU), cardiac surgery patients without prior atrial fibrillation or flutter were randomized to receive either dexmedetomidine (0.2-1.5 MUg/kg/h) or propofol (0.3-3 mg/kg/h) open-label titrated to a target Richmond agitation sedation scale of 0 to -3. Our primary endpoint was the incidence of postoperative atrial fibrillation, and the secondary end points were the length of ICU stay, length of hospital stay, and hospital costs. RESULTS: Atrial fibrillation occurred in 6 of 44 patients (13.6 %) in the dexmedetomidine group compared to 16 of 44 patients (36.4 %) in the propofol group (odds ratio = 0.28; 95 % confidence interval, 0.10, 0.80; P = 0.025). The median (interquartile range) length of ICU stay in the dexmedetomidine group was significantly lower than in the propofol group (2.9 (2.4-3.5) vs 3.5 (2.7-4.5 days, P = 0.008), with a trend toward a decrease in median hospital costs (86,367 vs 77,874 Chinese yuan; P = 0.068). The incidence of hypotension was higher in the dexmedetomidine group than in the propofol group (25/44 (56.8 %) vs 13/44 (29.5 %); P = 0.017). CONCLUSIONS: Dexmedetomidine sedation reduced the incidence of new-onset postoperative atrial fibrillation and shortened the length of ICU stay in patients after cardiac surgery compared to propofol sedation. Dexmedetomidine treatment was associated with more episodes of hypotension. TRIAL REGISTRATION: chictr.org.cn: ChiCTR-IPR-16008231 , retrospectively registered: April 6, 2016. This trial was not prospectively registered due to a lack of importance applied to trial registration. PMID- 27654701 TI - Aortic valve replacement in a patient with MPO-ANCA-positive Goodpasture disease. AB - Goodpasture disease (GD) is a rare autoimmune disorder characterized by the development of pathologic autoantibodies against both glomerular and alveolar basal membranes. Approximately one third of the patients with GD are also positive for anti-neutrophil cytoplasmic antibody (ANCA). In this case report, a 74-year-old woman was diagnosed as having myeloperoxidase (MPO)-ANCA-positive GD with severe aortic valve stenosis (AS). She underwent immunosuppressive therapy and plasmapheresis that led to GD remission. Whether a cardiac surgery affects a MPO-ANCA-positive GD in remission is unknown. We reported the outcomes after aortic valve replacement for severe AS in a patient with MPO-ANCA-positive GD. PMID- 27654702 TI - Targeting p21 activated kinase 1 (Pak1) to PAKup Pancreatic Cancer. PMID- 27654703 TI - Statistical Modelling and Characterization of Experimental mm-Wave Indoor Channels for Future 5G Wireless Communication Networks. AB - This paper presents an experimental characterization of millimeter-wave (mm-wave) channels in the 6.5 GHz, 10.5 GHz, 15 GHz, 19 GHz, 28 GHz and 38 GHz frequency bands in an indoor corridor environment. More than 4,000 power delay profiles were measured across the bands using an omnidirectional transmitter antenna and a highly directional horn receiver antenna for both co- and cross-polarized antenna configurations. This paper develops a new path-loss model to account for the frequency attenuation with distance, which we term the frequency attenuation (FA) path-loss model and introduce a frequency-dependent attenuation factor. The large scale path loss was characterized based on both new and well-known path-loss models. A general and less complex method is also proposed to estimate the cross polarization discrimination (XPD) factor of close-in reference distance with the XPD (CIX) and ABG with the XPD (ABGX) path-loss models to avoid the computational complexity of minimum mean square error (MMSE) approach. Moreover, small-scale parameters such as root mean square (RMS) delay spread, mean excess (MN-EX) delay, dispersion factors and maximum excess (MAX-EX) delay parameters were used to characterize the multipath channel dispersion. Multiple statistical distributions for RMS delay spread were also investigated. The results show that our proposed models are simpler and more physically-based than other well-known models. The path-loss exponents for all studied models are smaller than that of the free-space model by values in the range of 0.1 to 1.4 for all measured frequencies. The RMS delay spread values varied between 0.2 ns and 13.8 ns, and the dispersion factor values were less than 1 for all measured frequencies. The exponential and Weibull probability distribution models best fit the RMS delay spread empirical distribution for all of the measured frequencies in all scenarios. PMID- 27654705 TI - Corrigendum. PMID- 27654704 TI - Changes in Hospital-Physician Affiliations in U.S. Hospitals and Their Effect on Quality of Care. AB - Background: Growing evidence shows that hospitals are increasingly employing physicians. Objective: To examine changes in U.S. acute care hospitals that reported employment relationships with their physicians and to determine whether quality of care improved after the hospitals switched to this integration model. Design: Retrospective cohort study of U.S. acute care hospitals between 2003 and 2012. Setting: U.S. nonfederal acute care hospitals. Participants: 803 switching hospitals compared with 2085 nonswitching control hospitals matched for year and region. Intervention: Hospitals' conversion to an employment relationship with any of their privileged physicians. Measurements: Risk-adjusted hospital-level mortality rates, 30-day readmission rates, length of stay, and patient satisfaction scores for common medical conditions. Results: In 2003, approximately 29% of hospitals employed members of their physician workforce, a number that rose to 42% by 2012. Relative to regionally matched controls, switching hospitals were more likely to be large (11.6% vs. 7.1%) or major teaching hospitals (7.5% vs. 4.5%) and less likely to be for-profit institutions (8.8% vs. 19.9%) (all P values <0.001). Up to 2 years after conversion, no association was found between switching to an employment model and improvement in any of 4 primary composite quality metrics. Limitations: The measure of integration used depends on responses to the American Hospital Association annual questionnaire, yet this measure has been used by others to examine effects of integration. The study examined performance up to 2 years after evidence of switching to an employment model; however, beneficial effects may have taken longer to appear. Conclusion: During the past decade, hospitals have increasingly become employers of physicians. The study's findings suggest that physician employment alone probably is not a sufficient tool for improving hospital care. Primary Funding Source: Agency for Healthcare Research and Quality and National Science Foundation Graduate Research Fellowship. PMID- 27654706 TI - Open field exposure facilitates recovery from an aversive emotional event: Involvement of adrenergic and cholinergic transmitter systems. AB - Successive negative contrast (SNC) is an incentive relativity procedure that has been widely used to model emotional reactivity in rodents. The reward downshift experienced during SNC is thought to result in frustration. The exploration of a novel open field (OF), a complex situation involving stress induction and novelty detection, can enhance or block the acquisition of associative and non associative memories. Previous experiments found a modulatory effect of OF, applied before downshift trials, on SNC. This schedule, however, can affect retention performance by influencing attentional, motivational, motor or sensory perceptual mechanisms at training or retention testing. The use of post-training OF exposure avoids these confounds. This work assessed the effect of OF exposure after the acquisition of the downshifted memory, with the goal of targeting the consolidation of this mnemonic trace. We also investigated the involvement of the cholinergic and adrenergic systems in this phenomenon. The results indicated that OF facilitates recovery from reward loss and that both transmitter systems, cholinergic and adrenergic, play a role in this effect of OF. PMID- 27654707 TI - Protective Role of Corilagin on Abeta25-35-Induced Neurotoxicity: Suppression of NF-kappaB Signaling Pathway. AB - Aggregation and deposition of beta-amyloid peptides (Abeta), a pathological hallmark of Alzheimer's disease, has been recognized as a potent activator of neuroinflammation and neuronal dysfunction. In this study, the underlying molecular mechanisms responsible for the neuroprotective effects of corilagin against Abeta25-35-triggered neurotoxicity and inflammatory responses were investigated in PC12 cells. Pretreatment with corilagin effectively protected PC12 cells against Abeta25-35-induced damage and apoptosis. Abeta25-35 induced damage in PC12 cells as revealed by increased production of reactive oxygen species, caspase-3 activity, and cell cycle arrest was attenuated by corilagin pretreatment. Corilagin not only significantly suppressed the production of neurotoxic inflammatory mediators such as tumor necrosis factor-alpha, nitric oxide, and prostaglandin E2 but also downregulated cyclooxygenase-2 and inducible nitric oxide synthase expression in PC12 cells. It also exerted a beneficial effect by suppressing the degradation of inhibitor of kappaB (IkappaB)-alpha and subsequent activation of transcription factor nuclear factor kappaB (NF-kappaB), mostly through inhibition of extracellular signal-regulated kinase activity in comparison to c-Jun N-terminal kinase and p38 MAP kinase (p38) mitogen-activated protein kinase activity. These findings suggest that attenuation of Abeta25-35 induced inflammatory responses by downregulating the NF-kappaB signaling pathway might be a valuable strategy for both Alzheimer's disease prevention and/or treatment. PMID- 27654708 TI - Metabolic and Dynamic Profiling for Risk Assessment of Fluopyram, a Typical Phenylamide Fungicide Widely Applied in Vegetable Ecosystem. AB - Fluopyram, a typical phenylamide fungicide, was widely applied to protect fruit vegetables from fungal pathogens-responsible yield loss. Highly linked to the ecological and dietary risks, its residual and metabolic profiles in the fruit vegetable ecosystem still remained obscure. Here, an approach using modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction combined with GC-MS/MS analysis was developed to investigate fluopyram fate in the typical fruit vegetables including tomato, cucumber, pepper under the greenhouse environment. Fluopyram dissipated in accordance with the first-order rate dynamics equation with the maximum half-life of 5.7 d. Cleveage of fluopyram into 2-trifluoromethyl benzamide and subsequent formation of 3-chloro-5 (trifluoromethyl) pyridine-2-acetic acid and 3-chloro-5-(trifluoromethyl) picolinic acid was elucidated to be its ubiquitous metabolic pathway. Moreover, the incurrence of fluopyram at the pre-harvest interval (PHI) of 7-21 d was between 0.0108 and 0.1603 mg/kg, and the Hazard Quotients (HQs) were calculated to be less than 1, indicating temporary safety on consumption of the fruit vegetables incurred with fluopyram, irrespective of the uncertain toxicity of the metabolites. Taken together, our findings reveal the residual essential of fluopyram in the typical agricultural ecosystem, and would advance the further insight into ecological risk posed by this fungicide associated with its metabolites. PMID- 27654709 TI - Quantifying overlap between the Deepwater Horizon oil spill and predicted bluefin tuna spawning habitat in the Gulf of Mexico. AB - Atlantic bluefin tuna (Thunnus thynnus) are distributed throughout the North Atlantic and are both economically valuable and heavily exploited. The fishery is currently managed as two spawning populations, with the GOM population being severely depleted for over 20 years. In April-August of 2010, the Deepwater Horizon oil spill released approximately 4 million barrels of oil into the GOM, with severe ecosystem and economic impacts. Acute oil exposure results in mortality of bluefin eggs and larvae, while chronic effects on spawning adults are less well understood. Here we used 16 years of electronic tagging data for 66 bluefin tuna to identify spawning events, to quantify habitat preferences, and to predict habitat use and oil exposure within Gulf of Mexico spawning grounds. More than 54,000 km2 (5%) of predicted spawning habitat within the US EEZ was oiled during the week of peak oil dispersal, with potentially lethal effects on eggs and larvae. Although the oil spill overlapped with a relatively small portion of predicted spawning habitat, the cumulative impact from oil, ocean warming and bycatch mortality on GOM spawning grounds may result in significant effects for a population that shows little evidence of rebuilding. PMID- 27654710 TI - Nutrient status and phytotoxicity analysis of goat manure discharged from farms in South Korea. AB - The present study evaluated the phytotoxicity effect of goat manure (GM) collected from six different regions in South Korea, namely, Chupungnyeong (T1), Hoengseong (T2), Goesan (T3), Sancheong (T4), Jangsu (T5) and Namwon (T6). Phytotoxicity was assessed by means of the analysis of germination index (GI), relative seed germination (RSG), relative root elongation (RRE) and vigor index (VI) using five commercial crop varieties, namely, sesame (Sesamum indicum L.), chrysanthemum (Chrysanthemum indicum L.), carrot (Daucus carota), radish (Raphanus sativus) and cabbage (Brassica rapa). Physico-chemical parameter values were recorded at appreciable levels in all GM extracts. The effect of seedling growth was significantly different (p <= .05) due to the variability of nutrient content and phytotoxic effect of the extracts on the different crop seeds. Of the extracts, Goesan (T3) and Sancheong (T4) recorded the best results in the range of GI (%) (54.1-128.8) and VI (930.7-1044) and GI (%) (70.1-167.3) and VI (609.2 3034), respectively, and also showed no inhibitory effect in any of the crop seeds. Overall results also revealed that radish crops showed excellent and non phytotoxic results in all manure extracts compared to the other crops. PMID- 27654711 TI - Molecular Pathways: Targeting Steroid Receptor Coactivators in Cancer. AB - Coactivators represent a large class of proteins that partner with nuclear receptors and other transcription factors to regulate gene expression. Given their pleiotropic roles in the control of transcription, coactivators have been implicated in a broad range of human disease states, including cancer. This is best typified by the three members of the steroid receptor coactivator (SRC) family, each of which integrates steroid hormone signaling and growth factor pathways to drive oncogenic gene expression programs in breast, endometrial, ovarian, prostate, and other cancers. Because of this, coactivators represent emerging targets for cancer therapeutics, and efforts are now being made to develop SRC-targeting agents, such as the SI-2 inhibitor and the novel SRC stimulator, MCB-613, that are able to block cancer growth in cell culture and animal model systems. Here, we will discuss the mechanisms through which coactivators drive cancer progression and how targeting coactivators represent a novel conceptual approach to combat tumor growth that is distinct from the use of other targeted therapeutic agents. We also will describe efforts to develop next generation SRC inhibitors and stimulators that can be taken into the clinic for the treatment of recurrent, drug-resistant cancers. Clin Cancer Res; 22(22); 5403 7. (c)2016 AACR. PMID- 27654713 TI - Empirically Derived Relational Pattern Prototypes in the Treatment of Personality Disorders. AB - BACKGROUND: Patient transference patterns play a central role in the psychotherapy of personality disorders. OBJECTIVE: The aims of this study were to: (1) explore the relationship between patients' personality disorders and specific relational patterns and (2) construct empirically derived prototypes of relational patterns for each personality disorder. SAMPLING AND METHODS: A random national sample of 314 clinicians completed the Psychotherapy Relationship Questionnaire, which evaluates patients' relational patterns, and the Shedler Westen Assessment Procedure-200, which assesses personality disorders in a randomly selected patient currently in the clinician's care and with whom the clinician has worked for a minimum of 8 sessions and a maximum of 6 months (1 session per week). RESULTS: The avoidant/counterdependent transference pattern was associated with all cluster A personality disorders; the angry/entitled transference pattern was strongly positively associated with all cluster B personality disorders, and the anxious/preoccupied transference pattern was positively associated in a significant way with all cluster C personality disorders. Moreover, our empirically derived prototypes showed how the transference phenomena characteristic of each personality disorder are strongly coherent with the personality traits and mental and relational functioning of each specific disorder. CONCLUSIONS: The results strongly support a fundamental hypothesis that the patterns emerging in the therapeutic relationship are not arbitrary, and they clearly reflect patterns seen elsewhere in patients' lives that can be crucial to address. Regarding limitations, the same clinician provided data on both the personality pathology and the transference phenomena for each patient. PMID- 27654712 TI - Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer. AB - PURPOSE: This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery. EXPERIMENTAL DESIGN: Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-year overall survival were first identified as candidates for prognostic genes (156 genes, P < 0.001). We developed the recurrence risk score (RRS) by using quantitative RT-PCR to identify genes whose expression levels were significantly associated with YAP1 activation and patient survival in the training cohort. RESULTS: We based the RRS assay on 6 genes, IGFBP4, SFRP4, SPOCK1, SULF1, THBS, and GADD45B, whose expression levels were significantly associated with YAP1 activation and prognosis in the training cohort. The RRS assay was further validated in an independent cohort of 317 patients. In multivariate analysis, the RRS was an independent predictor of recurrence [HR, 1.6; 95% confidence interval (CI), 1.02-2.4; P = 0.03]. In patients with stage II disease, the RRS had an HR of 2.9 (95% CI, 1.1-7.9; P = 0.03) and was the only significant independent predictor of recurrence. CONCLUSIONS: The RRS assay was a valid predictor of recurrence in the two cohorts of patients with gastric cancer. Independent prospective studies to assess the clinical utility of this assay are warranted. Clin Cancer Res; 22(24); 6228-35. (c)2016 AACR. PMID- 27654716 TI - Epidemiology - Role of health professionals in prevention of disease. PMID- 27654715 TI - Compatibility of DNA IQTM, QIAamp(r) DNA Investigator, and QIAsymphony(r) DNA Investigator(r) with various fingerprint treatments. AB - Latent fingerprint and touch DNA are the two most important contact evidence for individualization in forensic science which provide complementary information that can lead to direct and unequivocal identification of the culprit. In order to retrieve useful information from both fingerprints and DNA, which are usually mingled together, one strategy is to perform fingerprint examination prior to DNA analysis since common DNA sampling technique such as swabbing could disturb or even destroy fingerprint details. Here, we describe the compatibility of three automatic DNA extraction systems, namely, DNA IQTM, QIAamp(r) DNA Investigator, and QIAsymphony(r) DNA Investigator(r), with respective to the effects of various fingerprint detection techniques. Our results demonstrate that Super Glue fingerprint treatment followed by DNA IQTM extraction shows better effectiveness in DNA profiling. Aluminum powder dusting offers the least interference to the three DNA extraction systems above. Magnetic powder dusting, on the other hand, strongly impedes DNA recovery. Physical Developer is the most intrusive, which yields profiles with poor quality, including lower peak heights, poor peak height ratios, and poor intra-color balance. In terms of the choice of extraction method, DNA IQTM system is recommended for sampling after fingerprint treatments, but not the two DNA Investigator systems. PMID- 27654717 TI - A national guideline and ILD PAK Registry Report: Recent landmarks in the understanding of interstitial lung diseases in Pakistan. PMID- 27654718 TI - Assessment of the dietary pattern of dormitory students in Kerman, Iran. AB - OBJECTIVE: Nowadays it is known that dietary imbalances are associated with non communicable diseases which would be a major cause of worldwide deaths in 2020. This study was conducted to assess the dietary pattern of students who live in a dormitory in Kerman, Iran, based on Healthy Eating Index-2005 (HEI-2005). METHODS: This cross-sectional study was conducted on 229 students who lived in the dormitory of Kerman University of Medical Science. The participants were recruited by multistage sampling. Their usual dietary intake was collected by using a valid food frequency questionnaire. The diet quality was calculated via HEI-2005. The HEI-2005 score was categorized into three groups: less than 50 (poor diet), between 50-70 (needs improvement) and more than 70 (good diet). RESULTS: The mean score of HEI-2005 in the present study was 64.22+/-8.98. 8.1% of the participants had poor diet, 63.4% had to improve their diet, and 28.5% enjoyed a good diet. The percent of energy intake from total fat, saturated fatty acid, solid fat and added sugar, and also sodium were significantly lower in the highest category of HEI-2005 than the lowest category. There was no significant difference in the intake of cholesterol, total vegetable and dairy products between the highest and lowest quartile categories. CONCLUSIONS: Majority of the participants need to improve their diet.Policy revisions and dietary interventions would require to promote diet quality and prevent non-communicable diseases in the future. PMID- 27654719 TI - Comparison of serum anti-mullerian hormone among fertile and infertile normal and diminished ovarian reserve groups. AB - OBJECTIVE: To compare anti-mullerian hormone among fertile and infertile groups of women in their reproductive age. METHODS: This case-control study was conducted at the Dow University of Health Sciences in collaboration with Civil Hospital, Karachi, from October 2011 to October 2012, and comprised fertile non pregnant and infertile women. Serum anti-mullerian hormone levels were measured in both the infertile and fertile groups. Blood samples to determine anti mullerian hormone levels were obtained irrespective of their menstrual cycle days. Infertile cases were further divided into two subgroups according to serum anti-mullerian hormone levels, into normal ovarian reserve group and diminished ovarian reserve group. SPSS 18 was used for data analysis. RESULTS: Of the 100 participants, 48(48%) women were fertile controls and 52(52%) were infertile. Of the latter, there were 30(57.69%) in the normal ovarian reserve group and 22(42.31%) in the diminished ovarian reserve group. The mean age of the participants was 26+/-4.026 years (range: 25-35 years). The mean values for the control, normal ovarian reserve and diminished ovarian reserve groups were 1.9+/ 0.16 ng/ml, 0.89+/-0.47 ng/ml and 2.0+/-0.6 ng/ml, respectively (p=0.001). CONCLUSIONS: Mean concentration of serum anti-mullerian hormone in infertile women with diminished ovarian reserve was significantly lower than that in normal ovarian reserve group and fertile control women. PMID- 27654714 TI - Medico-legal perspectives on sudden cardiac death in young athletes. AB - Sudden cardiac death (SCD) in a young athlete represents a dramatic event, and an increasing number of medico-legal cases have addressed this topic. In addition to representing an ethical and medico-legal responsibility, prevention of SCD is directly correlated with accurate eligibility/disqualification decisions, with an inappropriate pronouncement in either direction potentially leading to legal controversy. This review summarizes the common causes of SCD in young athletes, divided into structural (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, congenital coronary artery anomalies, etc.), electrical (Brugada, congenital LQT, Wolf-Parkinson-White syndrome, etc.), and acquired cardiac abnormalities (myocarditis, etc.). In addition, the roles of hereditary cardiac anomalies in SCD in athletes and the effects of a positive result on them and their families are discussed. The medico-legal relevance of pre-participation screening is analyzed, and recommendations from the American Heart Association and European Society of Cardiology are compared. Finally, the main issues concerning the differentiation between physiologic cardiac adaptation in athletes and pathologic findings and, thereby, definition of the so-called gray zone, which is based on exact knowledge of the mechanism of cardiac remodeling including structural or functional adaptions, will be addressed. PMID- 27654720 TI - The prevalence of autoantibodies among relatives for type 1 and 2 diabetic patients. AB - OBJECTIVE: To estimate the prevalence of islet cells autoantibodies among non diabetic relatives of type 1 and type 2 diabetic patients. METHODS: The study was conducted at the College of Medicinal Technology, Basra, Iraq, from December 2010 to December 2012, and comprised both diabetics and non-diabetics. The participants were first divided into two groups: type 1 diabetics; and type 2 diabetics. Both the groups had 2 sub-groups each; their non-diabetic relatives and non-relatives as controls. Laboratory investigations were done to estimate glutamic acid decarboxylase and islet cell antigen-2 autoantibodies by enzyme linked immunosorbent assay for all groups. Significant differences were assessed with chi-square test. RESULTS: Of the 300 subjects, 100(33.3%) were diabetics and 200(66.6%) non-diabetics. Among diabetics, 40(40%) had type 1 while 60(60%) had type 2 diabetes. Among type 1 diabetics, 27(67.5%) tested positive for glutamic acid decarboxylase autoantibodies compared to 15(25%) in type 2 diabetics, 6(15%) among relatives of type 1, 7(11.7%) among relatives of type 2 diabetic patients, and none among controls. Besides, 16(40%) of type 1 diabetic patients tested positive for islet cell antigen-2 autoantibodies compared to 8(13.3%) in type 2, and none in the sub-groups. CONCLUSIONS: The relatives of both types of diabetic patients showed immunity to islet cell autoantibodies which confirmed the effect of genetic factors in disease pathogenesis and may be important in disease prediction. PMID- 27654722 TI - Role of ascorbic acid supplement in amelioration of anaemia in lead intoxication. AB - OBJECTIVE: To assess anaemia and oxidative stress in rats that were injected lead and to evaluate the possible effects of ascorbic acid supplementation on these parameters. METHODS: This randomised control trial study was conducted at the Army Medical College, Rawalpindi, Pakistan, from October 2007 to September 2008, and comprised Sprague Dawley rats. The rats were randomly divided into three groups. The rats in Group 1 were given weekly injections of sodium acetate, and rats of Group 2 and 3 were given weekly injections of lead acetate. Ascorbic acid was supplemented in the drinking water of rats of Group 3. At the end of six weeks, terminal sampling was done and blood obtained was used to assess the serum malondialdehyde levels and red cell parameters. RESULTS: Of the 105 rats, each group had 35(33.33%). The overall mean age was 105+/-15 days and the mean weight was 225+/-25gm. The mean malondialdehyde level was 3.2+/-0.39 umol /L in Group 1, 7.8+/-0.48 in Group 2 and 3.8+/-0.34 in Group 3 (p<0.001). The mean haemoglobin level was 13.16+/-0.57 g/dL, 10.64+/-0.86 and 12.22+/-0.81, respectively (p<0.001). The red blood cells count was 7.63+/-0.33 106/uL in Group 1, 6.29+/ 0.54 in Group 2 and 6.83+/-0.45 in Group 3 (p<0.001). CONCLUSIONS: Administration of ascorbic acid in drinking water significantly reduced the oxidative stress and anaemia caused by lead intoxication. PMID- 27654721 TI - Metallo-beta-lactamase producing Escherichia coli and Klebsiella pneumoniae: A rising threat for hospitalized children. AB - OBJECTIVE: To determine the frequency of metallo-beta-lactamase (MBL) producing E.coli and Klebsiella pneumoniae, better phenotypic techniques for MBL detection and choices of treatment available for such cases. METHODS: This study was conducted in The Children's Hospital, Lahore during March, 2013 and February, 2014. A total number of 17,651 samples including blood, urine, CSF, pus and catheter tips from suspected cases of bacterial infections were processed and test organisms were identified using standardized microbiological techniques. MBL phenotypic identification was performed by Modified Hodge Test, Double Disc Synergy Test and Combined Disc Test. RESULTS: Carbapenem resistance was observed in 134/1168 (11.47%) strains which comprised of 89 (67.4%) Klebsiella pneumoniae and 45 (32.6%) E.coli. All of these carbapenem resistant isolates were found to be carbapenemase producers (CP) by MHT test. Among these CP strains, MBL was detected in 131/134 (97.8%) isolates both by CDT and DDST including 87 (66.4%) Klebsiella pneumoniae and 44 (33.6%) E.coli. Majority of these organisms were resistant to most of the antibiotics used in the study. The isolates showed good susceptibility to colistin (90.1%), chloramphenicol (60.3%) and fosfomycin(31%). CONCLUSIONS: Isolation of such a high number of MBL producers is a serious threat for hospitalized paediatric patients. PMID- 27654724 TI - Morbidity of colostomy reversal. AB - OBJECTIVE: To determine morbidity after colostomy reversal at a tertiary care hospital. METHODS: The retrospective case series was conducted at the Aga Khan University Hospital, Karachi, and comprised records of patients aged 15 years or more who underwent colostomy reversal from January 2003 to December 2011. Data was collected regarding demographics, procedure dates, indication, as well as type and location of colostomy. Details of colostomy reversal, including pre operative, intra-operative and post-operative variables were recorded. RESULTS: The mean age of the 96 patients was 40+/-16 years; 72(75%) of them being males. The most frequent indications for fashioning of colostomy were bowel perforation in 53 (55.2%) and malignancy in 9(9.3%) patients. Intra-operative complications occurred in 5(5.2%) with bowel perforation in 3(3.1%) and bleeding in 2(2%) patients. Overall, 40(41.6%) patients had post-operative local complications; the most common being wound infection in 19(19.8%) followed by incisional hernia 15(15.6%). Patients who experienced post-operative complications had significantly longer hospital stay compared to those without complications (9+/ 2.8 vs. 7+/-2.4days; p=0.038). CONCLUSIONS: Colostomy reversal was associated with non-negligible morbidity. The most common complications were wound infection and incisional hernia. PMID- 27654723 TI - Frequency of hyponatraemia and hypokalaemia in malnourished children with acute diarrhoea. AB - OBJECTIVE: To determine the frequency of hyponatraemia and hypokalaemia in malnourished children with acute diarrhoea. METHODS: This cross-sectional study was carried out at the Military Hospital, Rawalpindi, Pakistan, from September 2013 to March 2014, and comprised acute diarrhoea patients whose ages ranged from six months to five years. Blood samples for serum sodium and potassium were examined at the Armed Forces Institute of Pathology. Patients were labelled as having hyponatraemia, hypokalaemia, both or having normal serum sodium and potassium levels. RESULTS: Of the 80 patients, 49(61.3%) were boys and 31(38.7%) were girls with an overall mean age of 1.9+/-1.4 years. Besides, 41(51.3%) were aged below one year. The mean duration of diarrhoea was 3.2+/-1.7 days, with 53(66%) patients having the illness for 1-3 days. Hyponatraemia was observed in 26(32.5%) patients and hypokalaemia in 44(55%), whereas 10(12.5%) had no electrolyte imbalance. None of the participants had hypernatraemia or hyperkalaemia. CONCLUSIONS: Electrolyte disturbances among malnourished children may not be clinically evident, but diarrhoeal illness aggravated these imbalances. PMID- 27654725 TI - Serum anti-mullerian hormone: Correlation with the ovarian follicular dynamics in healthy mice. AB - OBJECTIVE: To evaluate the relationship between serum anti-Mullerian hormone and follicular dynamics in mice. METHODS: This experimental study was conducted in November, 2014 at the Dow University of Health Sciences, Karachi, and comprised laboratory-bred albino mice. They were sacrifised under anaesthesia and blood was collected via cardiac puncture to assess anti-Mullerian hormone while ovaries were collected for morphometric analyses. SPSS 19 was used for data analysis. RESULTS: There were 20 mice with a mean weight of 25+/-1.89 grams, while weight of the ovaries obtained from these mice was 9.6+/-0.92mg. The mean serum anti Mullerian hormone was 29.89+/-9.7ng/ml. On average, there were 87.8+13.54 primordial follicles, 51.85+/-8.36 primary, 20.35+/-5.57 secondary, 11.30+/-3.38 early antral and 3.05 +/- 1.27 late antral follciles (p<0.001; p=0.06).. CONCLUSIONS: Association of anti-Mullerian hormone with follicle dynamics reflected its role as a true ovarian reserve marker. Its assessment was of great significance in infertile women as well as young patients receiving chemotherapy. PMID- 27654726 TI - Fractionated stereotactic radiosurgery for vestibular schwannomas using cyberknife: A single institution experience. AB - OBJECTIVE: To assess tumour control, hearing preservation status, and complication ratio after fractionated stereotactic radiosurgery/radiotherapy by using CyberKnife device in patients with vestibular schwannomas. METHODS: This retrospective study was conducted at Izmir Ataturk Research and Tranining Hospital, Turkey, and comprised data of vestibular schwannomas patients treated with stereotactic radiosurgery/radiotherapy from March 2010 to December 2013. The patients were subjected to a dose ranging from 12 to 30Gy using CyberKnife system with an average of three fractions. SPSS 17 was used for data analysis. Paired t test and Pearson's chi-square test were used to compare clinical parameters between groups. P<0.05 was considered significant. RESULTS: Of the 41 patients, 26(63.4%) were women and 15(36.6%) were men. The median follow-up duration after stereotactic radiosurgery/radiotherapy was 25 months (interquartile range: 9-44 months). Radiographic control evaluation ratio was 95.7% with a median follow-up of 3 years (IQR: 18.5 months). Results of 23(56%) patients showed stabile response, 17(42%) regression response and 1(2%) progression response. There were no statistically significant changes between pre- and post-stereotactic radiosurgery/radiotherapy symptoms (p>0.05). One (2.4%) patient reported new onset facial paresis. CONCLUSIONS: Stereotactic radiosurgery/radiotherapy treatment of vestibular schwannomas resulted in a good ratio of tumour control. Hearing preservation status and ratios of toxicity were comparable to published literature. PMID- 27654727 TI - Academic performance of day scholars versus boarders in pharmacology examinations of a medical school in Pakistan. AB - Objective: To compare the academic performance of day scholar and boarder students in Pharmacology examinations. Methods: This comparative study was conducted at Rehman Medical College, Peshawar, Pakistan, from June to September, 2015. It comprised third-year medical students of the sessions 2013-14 and 2014 15.The record of the results of examinations, which had already been conducted, were assessed. All the exams had two components, i.e. multiple-choice questions and short-essay questions. Students were categorised into 4 groups according to their academic performance: those who got <50% marks (Group 1); 51-69% marks (Group 2); 70-80% marks (Group 3); and >80% marks (Group 4). SPSS 20 was used for data analysis. RESULTS: Of the 200 students, 159(79.5%) were day scholars and 41(20.5%) were boarders. In multiple-choice questions, 29(70.7%) boarder students were in Group 2, while none of them was in Group 4. In short-essay questions, 11(26.8%) of them were in Group 1 and 17(41.5%) in Group 2. Results of day scholars' multiple-choice questions exams showed 93(58.5%) were in Group 2 and 2(1.3%) in Group 4. In short-essay questions, 63(39.6%) were in Group 2 (p>o.o5 each). CONCLUSIONS: No significant difference was found between the academic performance of boarders and day scholars. PMID- 27654728 TI - Association of metabolic factors with dengue viral infection on admission triage which predict its clinical course during Lahore dengue epidemic. AB - OBJECTIVE: The study was done to identify metabolic factors which were associated with an increased risk of dengue haemorrhagic fever in clinically diagnosed patients of dengue viral infection. METHODS: 563 patients with dengue viral infection that presented to 3 tertiary care hospitals of Lahore were included in this study, out of which approximately half of the patients were diagnosed as dengue haemorrhagic fever. RESULTS: A total of 563 patients with 263(46.7%) dengue fever and 300(53.3%) dengue haemorrhagic fever patients were studied. The mean age of patients was 48.48 +/- 20.07 years. In patients younger than 60 (n=355), 171 patients had DF and 184 had DHF, while 116 patients above 60 years had DHF and 92 had DF (n=208). The presence of metabolic risk factors such as diabetes (OR = 2.146), hypertension (OR =1.65), diabetes and hypertension (OR =3.56), abnormal liver function tests (OR = 2.27), abnormal renal function tests (OR = 2.282) all increased the risk of DHF relative to DF. CONCLUSIONS: The study showed that metabolic factors especially diabetes with and without hypertension are important risk factors for the development of DHF. PMID- 27654729 TI - The effect of topical finasteride 0.5% on the outcome of diode laser therapy in the treatment of excess facial hairs in the women with hirsutism. AB - OBJECTIVE: To determine the effects of topical finasteride 0.5% on the results of diode laser therapy in the treatment of hirsutism. METHODS: This double-blind, placebo-controlled, clinical trial study was conducted at a private clinic in Babol, Iran, between June 2012 and July 2013, and comprised women with idiopathic hirsutism. A diode laser (810nm) treatment was applied monthly for 6 months with an extra session at the 12th month. The device was adjusted individually according to the skin types using Fitzpatrick classification. Patients were divided into 2 groups: those who were given topical finasteride 0.5% and those who were given placebo solution on a daily basis for 5 days before each session. RESULTS: Of the 104 participants, there were 52(50%) each in placebo and intervention groups. The mean age was 30.71+9.25 years in the former group and 31.55+/-7.72 in the latter (p=0.61). The mean hair number before treatment in the intervention group was 49.09+/-12.41 and in the placebo group was 48.78+/-15.31 (p=0.9). At the end of the 6-month period, the mean number in treatment and placebo groups were 3.26+/-1.01 and 5.23+/-1.73 (p<0.001), respectively. After a one-year follow-up, the mean hair count of 3.73+/-1.20 and 7.36+/-2.40 was attained in intervention and placebo groups (p<0.001) respectively. CONCLUSIONS: Applying finasteride 0.5% solution to the unwanted facial hairs and performing diode laser at the same area resulted in reduction of unwanted hairs. PMID- 27654730 TI - Protection of nurses rights in Turkey: A study on nurses' opinions. AB - OBJECTIVE: To evaluate nurses' opinions on the violation and protection of their rights at public hospitals. METHODS: The descriptive study was conducted between May and November 2013 at 11 hospitals affiliated with the Association of Public Hospitals in Istanbul, Turkey. Data was gathered using a questionnaire consisting of 59 questions on demographic characteristics, professions, and rights of nurses. RESULTS: Of the 1,808 respondents, 1,374(76%) said nurse's rights were not protected and 994(55%) believed that their rights were not protected at public hospitals. However, 1,027(56.8%) of the nurses stated that their right to job security was protected, while 1,448(80.1%) reported violation of their right to adequate pay and 1,289(71.3%) reported violation or non-recognition of the right to participate in the political decision-making processes that directly affect the nursing profession. Those who were middle-aged and those who had bachelor's degree believed their rights were not protected, and considered nursing as a weak profession that was unable to protect its rights (p<0.001). CONCLUSIONS: Nurses believed their rights, especially those about salary, were not sufficiently protected. PMID- 27654731 TI - False negativity in AFB Smear microscopy: An insight into the caveats of the most widely used screening tool for tuberculosis. AB - OBJECTIVE: To study the ratio of false negativity in sputum samples in diagnostic smears received for acid fast bacilli smear microscopy. METHODS: The retrospective cross-sectional study was conducted at the Ojha Institute of Chest Diseases, Karachi, and comprised specimens for microscopy and culture from presumptive tuberculosis patients for 38 months starting from November 2010.All laboratory investigations had been done as per the National Tuberculosis Control Programme guidelines. Statistical analyses were performed on MedCalc and Social statistics calculators, and Open Epi software. RESULTS: TOf the 2,158 specimens, 1,316(60.98%) were of men and 842(39.02%) of women (male-to-female ratio: 1.56:1). Besides, 843(39.06%) were smear-negative, of which 99(11.74%) were false negative. Of the 1,275(96.88%) men whose age was reported, 808(63.37%) were aged 19-45 years, whereas out of the 792(94.06) women whose age was known, 517(65.28%) were in that age group. Microscopic outcomes were significantly related to gender (p<0.001). CONCLUSIONS: Smear microscopy cannot be solely relied upon for diagnosis and its results must be correlated with additional clinical information and other diagnostics due to considerable amount of false negativity, especially in female population. PMID- 27654732 TI - Tuberculosis knowledge and health seeking behaviour: A tale of two districts of Sindh, Pakistan. AB - OBJECTIVE: To assess the knowledge about tuberculosis and health-seeking behaviour of people living in rural areas of Sindh. METHODS: This cross-sectional survey was conducted by the Pakistan Red Crescent Society in Dadu and Badin districts of Sindh, Pakistan, from January to August 2014. Cluster sampling technique was used for the selection of 900 households from two union councils. Those staying for less than 6 months and who refused to participate were excluded. Personal interviews were conducted by trained data collectors on pretested questionnaire. Data was analysed using SPSS 20. RESULTS: Of the 900 households, there were 450(50%) in each districts. In Dadu, 298(66.6%) participants were illiterate compared to 236(52.4%) in Badin. Half of the respondents n= 225 (50%) in Dadu were farmers compared to 136(30.2%) in Badin. Besides, 341(75.7%) in Dadu and 311(69%) in Badin were earning less than Rs10,000 per month. In addition, 318(70.6%) respondents in Dadu and 235(52.2%) in Badin had heard about tuberculosis. In Dadu, 237(52.6 %) thought it was curable compared to 263(58.4%) in Badin, whereas 32(7%) in Dadu and 45(10%) in Badin thought there was no remedy for it. Besides, 216(48%) villagers in both the districts were of the opinion that fever was the chief symptom, followed by cough and weight loss. Only 109(24.2%) respondents in Badin district confirmed the presence of a lady health worker in their village compared to 75(16.6%) in Dadu. CONCLUSIONS: Pakistanis living in rural areas had insufficient knowledge about most aspects of tuberculosis, and held misconceptions about the disease. PMID- 27654733 TI - Comparison of the safety and efficacy of single injection of subtenon triamcinolone and topical dexamethasone in reducing postoperative inflammation after phacoemulsification and intraocular lens implantation. AB - OBJECTIVE: To compare the safety and efficacy of single injection of sub-tenon triamcinolone and topical dexamethasone in reducing post-operative inflammation after phacoemulsification and intraocular lens implantation. METHODS: The randomised controlled study was conducted at Khyber Teaching Hospital, Peshawar, Pakistan, from September 2013 to February 2014. Patients who had undergone uneventful phacoemulsification with intraocular lens implantation by the same surgeon were included. Patients in Group A received 0.1% dexamethasone eye drops and those in Group B received sub-tenon triamcinolone injection (40mg/1ml). Follow-up was at 1st day, 14th day and 6 weeks post-operatively. At follow-up visit, grades of anterior chamber cells and aqueous flare were examined with slit lamp, and intraocular pressure was recorded. RESULTS: Of the 108 patients, each group had 54(50%) subjects. The mean age was 58.87+/-9.69 years (range: 33 to 84 years) in Group A and 57.77+/-8.93 years (range: 30 to 78 years) in Group B (p=0.544). On the first post-operative day, all the patients in both groups had some degree of inflammation in the anterior chamber. On the 14th post-operative day, anterior chamber cells were present in 4(7.4%) eyes in Group A and in 3(5.55%) eyes in Group B (p>0.999), while aqueous flare was present in 5(9.25%) eyes in Group A and 9(16.66%) eyes in Group B (p=0.391). Six weeks after the operation, no anterior chamber cells or aqueous flare was seen in any eye in either group. CONCLUSIONS: Sub-tenon triamcinolone injection was found to be a safe and effective alternative to topical dexamethasone for control of post operative inflammation after phacoemulsification. PMID- 27654734 TI - Effect of topical application of hard water in weakening of hair in men. AB - Background: Hard water is thought to play a key role in weakening of hair (not Hair Loss) and breakage especially when travelling is involved. In our community, commonly men do the travelling and complain more about hair problem which is why only young male individuals were included in this study. Materials and Methods: Water samples from different districts of KPK, Pakistan, were collected and their hardness values were estimated to find the water sample of maximum and minimum water hardness in order to know the maximum hardness hair would encounter in KPK, Pakistan. Samples from district Kohat had maximum hardness whereas minimum hardness was estimated in samples of district Peshawar. Water from district Kohat was considered as our sample water for the experimental group of hair. Hair samples were collected from 76 male individuals of district Peshawar, the area with least water hardness among the samples collected. Each hair sample was divided into two halves. One half was considered as experimental group and the other was considered as control group. The experimental group was treated with hard water of district Kohat for 10 minutes on alternate days, for 3 months. In a very similar way the control group was treated with de-ionized water. Tensile strength in term of "Stress" of both the experimental and control groups were measured using the universal testing machine and compared using paired t-test. Results and Conclusions: The standard deviations (SD) for hair treated with hard water and distilled water was 62.05 and 58.13 respectively and the mean values were 238.49 and 255.36 respectively. The results showed that the tensile strength of hair was significantly (p=0.001) reduced in hair treated with hard water as compared to hair treated with de-ionized water. PMID- 27654735 TI - SNP rs3088308 is a risk factor for poor lung function in healthy smokers. AB - OBJECTIVE: To see if single nucleotide polymorphisms of pulmonary innate immune molecule surfactant protein D were associated with poor lung function in smokers. METHODS: The study was conducted at Shaikh Zayed Hospital, Lahore, Pakistan, from April 2008 to August 2010, and comprised relatives and attendants of patients, as well as college and university students. Self-reported healthy smokers who demonstrated no airflow obstruction on spirometry were included. Deoxyribonucleic acid was extracted from their blood sample and genotyped for single nucleotide polymorphisms rs721917 and rs3088308 by polymerase chain reaction and restriction analysis. Serum was separated for measurement of surfactant protein D levels by a commercially available enzyme-linked immunosorbent assay based kit. Lung functions were compared between subjects possessing major and minor alleles using two-tailed Student's t-test. Multiple linear regression analysis was conducted to analyse the effect of age, smoking and the two single nucleotide polymorphisms on forced expiratory volume in 1 second. RESULTS: Of the 122 participants, all of whom were men, 98(80.33%) were smokers while 24(19.67%) had never smoked. Of the former, 90(91.84%) were current smokers and 8(8.16%) were ex-smokers. The overall mean age was 35.8+/-10.9 years. The mean surfactant protein D level was 121.4+/ 61.6ng/ml. In case of rs3088308, all lung function variables were reduced in patients with a minor allele and the results for forced expiratory volume in 1 second (p=0.016), forced expiratory volume in 1 second (%) predicted (p=0.009), forced vital capacity (p=0.048) and forced vital capacity (%) predicted (p=0.048) were statistically significant. Age had the highest influence on lung function (p<0.001) followed by smoking status (p=0.04) and single nucleotide polymorphisms rs3088308 minor allele (p=0.04). CONCLUSIONS: Single nucleotide polymorphisms rs3088308 was found to modulate serum surfactant protein D levels and may be a risk factor for development of chronic obstructive pulmonary disease among smokers. PMID- 27654737 TI - Innovation in ethics and professionalism course: Early experience with portfolio workbook. AB - OBJECTIVE: To analyse students' perception regarding the use of portfolio workbook in ethics course. METHODS: This mixed method study was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, in 2014, and comprised fourth year medical students. The "portfolio-workbook", developed on principles of cognitive load and guided learning theories, contained essential reading material. Learning sessions were also facilitated by teaching tools like role plays, movie/video clips, vignettes, etc., followed by reflective writing exercises. Feedback questionnaire with open- and closed-ended questions was used to collect data. Quantitative data was analysed for frequencies and percentages. Content analysis was conducted for the open-ended responses. RESULTS: Of the 20 participants, 10(50%) considered using portfolio-workbook as difficult initially. However, on completion of module 16(80%) found it easy. Moreover, 17(85%) appreciated it as a learning tool. Besides, 19(95%) students found teaching videos and 13(65%) found open discussions as effective learning tools. Portfolio workbook as an assessment tool was preferred by 19(95%) students. CONCLUSIONS: The use of portfolio-workbook in teaching ethics to undergraduates was found to be encouraging as it generated interest and interaction. PMID- 27654736 TI - Long-term results of reverse Liss plate applied to unstable proximal femur extracapsular fractures in Istanbul, Turkey. AB - OBJECTIVE: To evaluate the results of the minimally invasive internal fixation method using reverse Less Invasive Stabilisation System locking plate in unstable proximal femur extracapsular fractures. METHODS: The retrospective study was conducted at Department of Orthopaedics in Taksim Training and Research Hospital (Istanbul, Turkey) and comprised data of patients in whom osteosynthesis was applied with reverse Less Invasive Stabilisation System locking plate for an unstable extracapsular femur fracture between September 2006 and June 2011. Evaluation was made of the fracture reduction quality and degrees of varus-valgus and anteversion-retroversion on the postoperative radiographs which were compared to the healthy hip. At the final follow-up examination, evaluation was made using the Harris Hip Score and Visual Analogue Scale score. The follow-up period ranged from 12 to 35 months. RESULTS: Of the 42 patients, 16 (38%) were females and 26 (62%) were males, with an overall mean age of 64.2+/-22.25 years (range: 23-97 years). The trauma was low-energy in 24 (57%) patients and high-energy in 18 (43%). Union was achieved in 38 (90%) patients with secondary bone healing in mean 14 weeks (range: 12-20 weeks). Complications were seen in 4 (9%) patients and additional surgical interventions were made. Radiographically, reduction was anatomic in 33 (79%) patients, acceptable in 8 (19%) and poor in 1 (2%). At the 12-month follow-up, the mean Harris Hip Score was 88,6 (range: 59-100) and mean Visual Analogue Scale score was 2.19 (range: 0-9). CONCLUSIONS: In the surgical treatment of unstable extracapsular proximal femur fractures, reverse Less Invasive Stabilisation System plate could be easily applied with a minimally invasive fixation method as an alternative to other treatment methods with successful results. PMID- 27654738 TI - Nutrition in intensive care in adults review of the literature and development of evidence based feeding protocols. AB - The subject of nutrition in intensive care is broad.Thenutrition support therapy plays a crucial role in the management of critically ill patients. This review was carried out to address the existing controversies and to recognise the current practice guidelines for the management of nutrition in intensive care units (ICUs) in adults. A PubMed search was carried out for clinical trials addressing the current nutrition practice in ICUs, recommendations for calculating energy requirements and efficacy of an algorithmic approach to nutritional delivery in an ICU setting. Algorithms were developed and modified for the practice of nutrition in an adult ICU in a quaternary care hospital in Pakistan. PMID- 27654739 TI - Socio-economic, environmental and demographic determinants of rise in obesity among Pakistani women: A Systematic Review. AB - Nutrition transition is a shift in eating and disease patterns towards diet nutrition-related non-communicable diseases (NR-NCDs). This shift in many developing countries has been accompanied with changes in behaviours, lifestyles, diets, physical inactivity, smoking and alcohol consumption. In addition to the burden of under-nutrition, nutrition transition has caused a sudden rise in overweight/obesity-related chronic diseases in developing countries. Little research has been done in Pakistan to explore nutrition transition, and its associated nutrition challenges. The current study attempted to investigate the socio-economic, environmental and demographic determinants of rise in obesity among women of reproductive years (15-49 years) in Pakistan. A review of related published literature for a period of 10 years (2005-2015) was carried out. Also, data from National Nutrition Survey (NNS-2011) and Pakistan Demographic and Health Survey (PDHS 2012-13) was reviewed and used to supplement the published researches from Pakistan. For this purpose, a computer-based search was performed on PubMed and PubGet to retrieve relevant articles. The major socio-economic and environmental risk factors contributing to the risk of obesity among Pakistani women were sedentary lifestyle, lack of awareness, higher rates of urbanisation along with shift in dietary pattern from high-fibre diet to low-fibre, and high calorie diet. The results of this review highlight the need for designing and implementing of national nutrition policy focussed on improving the awareness of determinants and consequences of nutrition-related illness in Pakistan. PMID- 27654740 TI - Spectrum of abdominal-tuberculosis in emergency surgery: 100 cases at a tertiary care Centre Dow University of Health Sciences and Civil Hospital Karachi, Pakistan. AB - The study highlights the spectrum of abdominal TB in emergency surgery and its outcome. A proforma based prospective cross sectional study was conducted from March 2008 - March 2014, at the Department of General Surgery, Dow University of Health Sciences & Civil Hospital Karachi, Pakistan. Total patients studied were hundred. Ninety percent patients presented through the emergency department. Mean age was 30 +/- 7.29 years. Family history of TB was positive in 46 (46%) patients. Pulmonary TB was present in 22 (22%), and 52 (52%) - were already on Antitubercular Therapy-- Emergency exploratory laparotomy was performed in 85 (85%) patients with 61 (61%) having peritonitis. and 24 (24%) having acute intestinal obstruction. A total of 15 (15%) patients were kept on ATT under observation, Of these 7(7%) were diagnosed with Ileocaecal mass, 5 (5%) with enterocutaneous fistula, and 3(3%) had sub-acute intestinal obstruction. Ileum was the most common site for abdominal TB in 36(36%), followed by ileocaecal TB in 13 (13%) and jejunal TB in 12 (12%). Stoma and abdominal washout was the minimum procedure which was performed in 34 (34%) cases. Fourteen (14%) patients diagnosed with ileocaecal TB, received limited right hemi colectomy with two end stoma whereas 7(7%) patients were subjected to limited right hemi colectomy with primary anastomosis. Patients with multiple strictures and perforations were subjected to segmental resection with two end stoma. This was performed, in 12 (12%) cases and primary repair and anastomosis in 9 (9%). Only washouts and laparostomy was performed in 5 (5%) and adhenolysis in 4(4%) cases. Redo surgery was required in 44 (44%). The overall mortality was 18%. This study concludes that abdominal TB patients usually present late with complications in emergency surgery because of diagnostic delay, having a high morbidity and mortality. PMID- 27654741 TI - Intraoperative ventilatory management of adult tracheoesophageal fistula. AB - Iatrogenic Tracheo Esophageal Fistula (TEF) in adults is a rare complication occurring secondary to trauma and prolonged intubation. There is very scarce data regarding its airway management and that too is from the paediatric age group. We describe the case of a young male undergoing TEF repair. We started with routine tracheal intubation but during surgery our tracheal tube was hindering surgical repair. So we used intermittent ventilation by passing the tracheal tube distal to the fistula and then pulling it back and providing clear surgical field during apnoea. It was done several times until the repair was completed successfully. Different airway management techniques are described in literature with the most common being oral intubation and placement of cuff distal to the fistula. However it may need to be modified according to the situation. We used a different technique for ventilation and will discuss it's pros and cons. PMID- 27654742 TI - Successful management of septic patient with concealed left persistent superior vena cava: anaesthetic perspective. AB - Surviving sepsis guideline supports the placement of central venous cannulation (CVC) to target the deranged physiology. The placement of CVC is still challenging, which requires detailed knowledge of venous anatomy and orientation of congenital venous anomalies. Double or persistent left superior vena cava (PLSVC) is a common anomaly in thoracic venous system. Our patient had hidden PLSVC, though he was previously asymptomatic with no cardiac disease. We report the successful anaesthetic management of an adult male with septicaemia for emergency laparotomy. CVC was placed in left internal jugular vein under vision by ultrasonography for fluid and vasopressor requirement. The incidental PLSVC was initially diagnosed on routine post procedure chest X-ray. Later it was confirmed by transthoracic echocardiography with an agitated saline micro bubbles contrast media.We conclude that the routine post CVC chest X ray is mandatory not only to identify the correct positioning of CVC placement but also very helpful in identifying the underlying rare anomalies. PMID- 27654743 TI - Sudden-onset paraplegia during pregnancy caused by haemorrhage in a spinal cord haemangioblastoma: A case report. AB - Spinal cord haemangioblastomas are rare central nervous systems tumours, and haemorrhage.It is an uncommon occurance. We report a 28-year-old pregnant patient who presented with paraplegia due to acute haemorrhage of a spinal haemangioblastoma. Magnetic resonance imaging showed extensive syrinx cavities, an intramedullary lesion at the T4-T5 spinal cord level e, and a subarachnoid haemorrhage. Digital subtraction angiography showed the feeding artery and dilated tortuous draining vein within the dural sac. The lesion was deemed a haemangioblastoma. The histopathological examination confirmed the diagnosis. Postoperatively, the paraplegia improved and the patient was able to walk within 2 weeks. Imaging is important for early diagnosis to prevent patients persistent neurological deficits. PMID- 27654744 TI - Reattachment of a partially amputated ear without microsurgery. AB - Traumatic ear amputations are relatively rare. Whenever possible, ear re implantation should be attempted; however the choice of the surgical procedure must be judicious. In the current report, a case of complete non-microsurgical salvage of a partially amputated ear treated by the pocket technique described by Mladick was presented. The surgical technique is described in detail by serial photographs, along with the postoperative management and outcome of the patients. The revascularisation of the severed part was successful. Morphological result was very good when the ear was freed from the pocket. We recommend the Mladick's procedure for reimplantation of fragments less than 1/2 of the auricle with favourable tissue condition. PMID- 27654745 TI - The different cutaneous presentations in three cases of Kawasaki disease as confounding factor of diagnosis. AB - We report three paediatric cases of Kawasaki disease (KD). Erythema multiforme (EM) was the presenting cutaneous feature in two patients, with young age (43 days old), macular rash and meningitis in the third patient. Diagnosis of KD was difficult due either to initial misdiagnosis of drug eruption, incomplete presentation, or the young age of the patient. Clinicians should be aware of these cutaneous presentations to prevent KD complications. PMID- 27654746 TI - Recent advance in lipid management: Focus on PCSK9I (Proprotein Convertase Subtilisin/ Kexin 9 Inhibitors). AB - This review discusses recent advances in lipid management, focusing on a new class of drugs known as pcsk9i (proprotein convertase subtilisin/ kexin 9 inhibitors. It describes the basic and clinical pharmacology of these drugs. PMID- 27654747 TI - Diabetic tuberculosis. AB - Diabetes and tuberculosis coexist together, and influence each other's natural history and treatment outcomes significantly. This assumes clinical as well as public health significance. This article describes these associations, and discusses action that can be taken at the primary care level to tackle this challenge. PMID- 27654748 TI - Sports-related concussion awareness in Pakistan. PMID- 27654749 TI - Infantile metachromatic leukodystrophy in an 18 month old girl. AB - Metachromatic leukodystrophy is a rarely occurring neurodegenerative metabolic disorder with an incidence of 1-9 individuals out of 1,000,000. We present a similar case in an eighteen month old child which was extremely challenging to diagnose. Clinical symptoms suggested motor regression and developmental delay which gave rise to suspicion of a neurodegenerative disorder. An MRI scan of the brain revealed cortical demyelination with tigroid appearance which confirmed the diagnosis of Metachromatic leukodystrophy. Due to the lack of availability of a treatment option like bone marrow transplant, the patient could only be given physiotherapy to help with the musculoskeletal manifestations of the disorder. The purpose of this case report is to identify clinical presentation and classical MRI findings to diagnose MLD in absence of enzyme assay and gene mutation analysis. PMID- 27654751 TI - Pulsed dye laser treatment of primary cryptococcal laryngitis: A novel approach to an uncommon disease. AB - An 82-year-old supplemental oxygen dependent woman with severe COPD presented with an eight month history of worsening hoarseness and stridor. Office laryngoscopy revealed laryngeal edema and ulcerative masses throughout the larynx. In-office biopsies were positive for Cryptococcus neoformans. This report details a novel approach to the treatment of cryptococcal laryngitis, a combination of in-office pulsed-dye laser (PDL) ablation and medical therapy. Despite treatment with oral fluconazole, the recommended treatment for cryptococcal laryngitis the patient continued to be symptomatic with dysphonia and throat discomfort. Repeated laryngeal exam demonstrated persistent cryptococcal nodules. The patient was subsequently effectively treated with an in office PDL laser. This case demonstrates the efficacy of in-office laser treatment for residual laryngeal Cryptococcus. For patients like this one, who have failed medical therapy and are unfit for general anesthetic, the in-office laser provides an excellent alternative treatment approach. PMID- 27654752 TI - Primary open-angle glaucoma. PMID- 27654753 TI - The right kind of support? AB - When is a nursing skill not a nursing skill? When ir's a task undertaken by a health care assistant? PMID- 27654750 TI - Generation of biallelic knock-out sheep via gene-editing and somatic cell nuclear transfer. AB - Transgenic sheep can be used to achieve genetic improvements in breeds and as an important large-animal model for biomedical research. In this study, we generated a TALEN plasmid specific for ovine MSTN and transfected it into fetal fibroblast cells of STH sheep. MSTN biallelic-KO somatic cells were selected as nuclear donor cells for SCNT. In total, cloned embryos were transferred into 37 recipient gilts, 28 (75.7%) becoming pregnant and 15 delivering, resulting in 23 lambs, 12 of which were alive. Mutations in the lambs were verified via sequencing and T7EI assay, and the gene mutation site was consistent with that in the donor cells. Off-target analysis was performed, and no off-target mutations were detected. MSTN KO affected the mRNA expression of MSTN relative genes. The growth curve for the resulting sheep suggested that MSTN KO caused a remarkable increase in body weight compared with those of wild-type sheep. Histological analyses revealed that MSTN KO resulted in muscle fiber hypertrophy. These findings demonstrate the successful generation of MSTN biallelic-KO STH sheep via gene editing in somatic cells using TALEN technology and SCNT. These MSTN mutant sheep developed and grew normally, and exhibited increased body weight and muscle growth. PMID- 27654754 TI - Calling the tune. AB - Most sports fans are aware that fltheir heroes frequently carry advertising logos on their shirts and that a good many sporting occasions are heavily sponsored. Indeed, it would be a pointless exercise (from the sponsors' point of view) if the fans weren't a ware of the fact; the object of the sponsorship being advertising of some product or service. PMID- 27654755 TI - Bandages and bandaging. AB - The first official British standards for bandages appeared in a supplement to the 1911 British Pharmaceutical Codex (BPC) which included a specification for crepe bandage, as well as monographs for simple non-extensible products such as calico, flannel, domette and open-wove bandages. These bandages had a simple retention function although they also provided warmth and protection. PMID- 27654757 TI - ? AB - Back to the future: Nurse Corrin Cameron marked the 150th anniversary of King's College Hospital in South London by burying a lime capsule' in the foundations of the new day surgery centre where building work began last month as part of the King's 2000 project. The package includes equipment dating back to the beginning of the century as w ell as modern medical items. PMID- 27654756 TI - Students move to block poll tax payments. AB - Maverick Confederation of Health Service Employees (COHSE) student nurses are advocating non-poll tax payment and attempting to block court orders, contrary to national union policy. PMID- 27654759 TI - Paediatric oncology ward gets all clear. AB - Nursing staff at tuberculosis-struck Alder Hey Hospital's paediatric oncology ward were last week given the all clear after one child died of the disease. PMID- 27654760 TI - Planning dilemma over new P2000 courses. AB - Project 2000 colleges face crippling planning difficulties because the health department is refusing to say whether they will ever run the new courses. PMID- 27654761 TI - Report describes 'wholly unacceptable' facilities. AB - Conditions on a Merseyside psychiatric ward have been condemned as 'wholly unacceptable', with peeling walls and insufficient facilities. PMID- 27654764 TI - ENB warns of district nurse training crisis. AB - District nursing is facing decimation as health authority funding continues to shrink, the English National Board warned last week. PMID- 27654762 TI - Major review anticipated from new group. AB - The future of mental handicap nursing after the Government's community care changes are implemented is to be investigated by a newly-established Department of Health working group. PMID- 27654765 TI - Committee criticises uncertainty over care funding. AB - A Tory-dominated parliamentary committee has called the Government's funding arrangements for the community care reforms 'far from satisfactory'. PMID- 27654767 TI - Clinical comparison of a new compression bandage. AB - A t a recent multidisciplinary symposium on venous ulceration sponsored by the Department of Health, it was stated that the estimated cost to the Health Service of treating leg ulcers was L300 to L600 million per year, similar to the cost of tobaccorelated disease ( 1 ). PMID- 27654768 TI - Reform plans left to gather dust. AB - Plans to reform Northern Ireland's nurse management have been virtually left to gather dust since the early 1980s, according to a scathing new report from the Province's Audit Office. PMID- 27654769 TI - Double poll tax charge could be abolished. AB - The double poll tax charge on property- owning nurses who rent hospital accommodation could be abolished, following a precedent-setting appeal last week. PMID- 27654772 TI - Eire. AB - Radical action is needed to deal with acute nursing shortages and widespread nurse emigration from Ireland, the Irish Nurses' Organisation General Secretary P Maddon has claimed. PMID- 27654771 TI - ? AB - The echo of former times: delegates test out the acoustics of the Devonshire Royal Hospital's dome during a Nursing Standard Stockport, Tameside and Glossop College of Nursing rehabilitation conference in Buxton, Derbyshire. PMID- 27654774 TI - Ussr. AB - Thousands of mentally abnormal children in the Soviet Union have been disowned by their parents and dumped in institutions for most of their lives, a report in The Times claims. PMID- 27654773 TI - Need for battle over contract involvement. AB - Nurses may not like the Government's health service reforms but they must ensure they are there when contracts arc- drawn up and decisions made, Jane Salvage, Director of Nursing Developments at the King's Fund has warned. PMID- 27654775 TI - Posthumous regional appeal upheld. AB - A nurse who died earlier this year has been posthumously awarded a higher grade in a South West Thames regional appeal. PMID- 27654776 TI - France. AB - A former French health minister has called on the French Government to reopen Paris brothels to fight AIDS. PMID- 27654777 TI - Parliament. AB - Proposals to split the Social Services Select Committee in two look set to spark off a new political power struggle. PMID- 27654778 TI - Setting standards: pressure sores. AB - In 1989, a small working party was convened to develop standards for the prevention, detection and treatment of pressure sores as part of the district's quality assurance programme. The working party began its task by addressing a number of key interrelated issues, including the nurses' responsibility in exercising professional accountability. Accountability was defined as assuming responsibility for the goals, methods and patient outcomes of any nursing intervention. Second, the problems associated with continuity of care, long recognised by both patient and nurse were considered. PMID- 27654783 TI - Pill conference marks contraceptive changes. AB - Scientists last week heralded a brave new world in contraceptive techniques but warned that some of the developments I may not be available for decades. PMID- 27654782 TI - Free guide to diabetes mellitus management. AB - A new desk-top guide to the diagnosis and management of non-insulin dependent diabetes mellitus is available free to nurses and doctors. PMID- 27654784 TI - Some screening is 'a costly waste of time'. AB - Some health screening is a costly waste of time that can even do positive harm, health service managers were warned recently. PMID- 27654785 TI - Health record aims to give power to parents. AB - The widespread introduction of a new, parent-held, child health record would be the most significant step in child health since the introduction of vaccinations, according to a joint working I party on child health surveillance. PMID- 27654786 TI - Toxic shock syndrome warning over tampons. AB - Sanitary tampons can still cause toxic shock syndrome, according to two doctors writing in the British Medical Journal. PMID- 27654787 TI - Crisis ahead. AB - Poorly-prepared health authorities may ' be heading for disaster when they begin to introduce the health care assistant grade later this year. PMID- 27654788 TI - Tapping the potential. AB - Scan McCarthy looks smart and confident as he goes about his work on a busy medical ward at King's College Hospital, London. The patients call him 'nurse', quite unaware rhat he is one of a new breed of NHS stalf: a health care assistant. Sean left a career in retail management to do his training with Camberwell Health Authority, which already has 65 health care assistants in post. PMID- 27654789 TI - Taking reforms on trust. AB - When the Parliamentary battle over the National Health Service reforms is sealed with Royal Assent next month, a new fight begins. PMID- 27654790 TI - Listings. PMID- 27654791 TI - Information for Peto's sake. AB - Conductive education for motor-disordered children and adults as practised at Hungary's world-famous Peto Institute may be the cause of excitement among Nursing Standard readers - and some confusion too. PMID- 27654792 TI - No grade mix for paediatric wards. AB - I was interested to read James Buchan's article 'Grade mix' - Nursing StandardMay 16-22. I was extremely concerned, however, to note that, according to statistics recently published by the Department of Health, learners only comprise five per cent of nursing staff in the area of paediatric nursing. The number of nurse learners working in paediatric wards varies markedly between paediatric wards in district general hospitals (where learners are undergoing general training) and children's hospitals (where learners are undergoing both paediatric and general nurse training courses). PMID- 27654793 TI - HIV and AIDS nurses' forum. AB - The first meeting of a London forum for nurses working with HIV and AIDS was held on Wednesday June 6 in James Pringle House, Middlesex Hospital. Fifty people attended the meeting representing over 20 different HIV and AIDS units around London. It was recognised that there is a need for a specific information/support group for nurses in this field. It was agreed that the group should meet monthly on the first Wednesday of each month, with a different ward or other agency providing the venue each time. PMID- 27654795 TI - Crossword. PMID- 27654794 TI - ? AB - "He's agreed to try it, but don't think he's very enthusiastic about holistic medicine". PMID- 27654796 TI - Having the EN face that fits. AB - I felt I must write a reply to the latest letter on enrolled nurse conversion courses - especially in reply to Wendy Larsen's letter (Nursing Standard May 30 - June 5). PMID- 27654797 TI - Information exchange. AB - * J Chambers I am a ward sister in a private hospital which uses a daily labour management system to reduce or increase the number of nursing hours according to the number of patients. PMID- 27654799 TI - ? AB - * Does anybody have any clinical evidence of anybody contracting HIV from a toilet seat? PMID- 27654798 TI - The low down on BSE. AB - The comment in Nursing Standard May 23 - 29 regarding bovine spongiform encephalopathy (BSE) will do little to enhance the standing of the nursing profession. PMID- 27654800 TI - Romanian insightFollowing her recent visit to Romania, Nursing Standard Editor Norah Casey gives an insight in words and pictures into a school for educationally and culturally deprived children in Bucharest. AB - One of the first visits I made was to a school for educationally deprived children in the centre of Bucharest. There were almost 250 children there, from the age of five upwards. Even the enthusiasm of the staff could not mask the squalor of the building these children were taught in. PMID- 27654801 TI - Towards a new era. AB - 'Selling' the Royal College of Nursing to politicians and public is arguably the most important non-nursing job within the RCN. And stepping straight into nursing's complex professional issues and inter-relationships could provide a minefield of misconceptions to any lay person taking on the role. PMID- 27654802 TI - Coping with Bereavement S Horn Coping with Bereavement Thorsons 128pp L4.99 0 7225-1651-7. AB - Bereavement is any sense of loss often linked to a major life event eg, redundancy, changing job, infertility, chronic disease, illness. PMID- 27654803 TI - Males at Risk Males at Risk F G Bolton et al SAGE 222pp L13.95 0-8039-3237-5. AB - Males at Risk sets out to destroy the myth that it is mainly female children at risk from sexual abuse. PMID- 27654804 TI - Who Cares Who Cares P Mares BBC/KFC 22pp L9.50 1-870551-99-0. AB - Penny Mares' handbook and Jonathan Miller's video are from the King's Fund Centre and the BBC TV series Who Cares. PMID- 27654805 TI - 'I've got to prioritise': being a parent with cystic fibrosis. AB - Due to advances in earlier diagnosis and treatment, the life expectancy of a person born with cystic fibrosis (CF) has increased. Therefore, more people with CF are becoming parents but the psychological understanding of CF has lagged behind advances in medical treatment; there is very limited applied psychological research on which parents and professionals can draw when considering issues of parenting in this context. This qualitative research explored how mothers and fathers with CF experience and manage the dual roles of being a parent and living with CF. The aim was to facilitate development of an understanding of experience rather than test existing theory. A qualitative methodology was chosen as it allowed participants to reflect openly on their individual experiences. Nine participants completed semi-structured interviews either in their own homes or a clinic base which examined parenting, CF and the interaction between the two roles. Four participants were male and five were female with an age range of 21 50. Interpretive Phenomenological Analysis was used to interpret the participants' accounts and generate super-ordinate and master themes. 'Being a parent on compressed time' was the super-ordinate theme which reflected the challenge of parenting within both a limited life trajectory and a complex treatment regime with daily adherence and time pressures. The findings have implications for parents with CF, those considering parenting and for health professionals working in CF services whose guidance needs to be grounded in an evidence-base. Further research is needed to explore the experiences of parents within different family structures, parents who have had a transplant and the perspectives of others in the wider system in which parents with CF are located. PMID- 27654806 TI - DNA Microarray Platform for Detection and Surveillance of Viruses Transmitted by Small Mammals and Arthropods. AB - Viruses transmitted by small mammals and arthropods serve as global threats to humans. Most emergent and re-emergent viral agents are transmitted by these groups; therefore, the development of high-throughput screening methods for the detection and surveillance of such viruses is of great interest. In this study, we describe a DNA microarray platform that can be used for screening all viruses transmitted by small mammals and arthropods (SMAvirusChip) with nucleotide sequences that have been deposited in the GenBank. SMAvirusChip was designed with more than 15,000 oligonucleotide probes (60-mers), including viral and control probes. Two SMAvirusChip versions were designed: SMAvirusChip v1 contains 4209 viral probes for the detection of 409 viruses, while SMAvirusChip v2 contains 4943 probes for the detection of 416 viruses. SMAvirusChip was evaluated with 20 laboratory reference-strain viruses. These viruses could be specifically detected when alone in a sample or when artificially mixed within a single sample. The sensitivity of SMAvirusChip was evaluated using 10-fold serial dilutions of dengue virus (DENV). The results showed a detection limit as low as 2.6E3 RNA copies/mL. Additionally, the sensitivity was one log10 lower (2.6E2 RNA copies/mL) than quantitative real-time RT-PCR and sufficient to detect viral genomes in clinical samples. The detection of DENV in serum samples of DENV infected patients (n = 6) and in a whole blood sample spiked with DENV confirmed the applicability of SMAvirusChip for the detection of viruses in clinical samples. In addition, in a pool of mosquito samples spiked with DENV, the virus was also detectable. SMAvirusChip was able to specifically detect viruses in cell cultures, serum samples, total blood samples and a pool of mosquitoes, confirming that cellular RNA/DNA did not interfere with the assay. Therefore, SMAvirusChip may represent an innovative surveillance method for the rapid identification of viruses transmitted by small mammals and arthropods. PMID- 27654807 TI - Interprofessional management of concussion in sport. AB - Due to the high incidence of sports concussion, various health and medical providers are likely to encounter athletes who have sustained such an injury. Management of concussion necessitates coordinated care by the members of the sports medicine team due to its pathophysiology and complexity of management during recovery. All members of the sports medicine team must possess contemporary knowledge of concussion management as well as strong interprofessional communication skills to ensure effective care and safe return to sports participation. Therefore, the aim of this manuscript is to review the current best practices in interdisciplinary management of sports concussion with a special emphasis on the required interprofessional communication among the sports medicine team. PMID- 27654808 TI - Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation. AB - To explore pre-transplantation prognostic factors for adult T-cell leukemia lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status >=2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score >=3, European Group for Blood and Marrow Transplantation (EBMT) risk score >=5, HSCT from an HLA mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level >=10,000 U/mL, lymphocyte count >=4000/MUL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT. PMID- 27654810 TI - In vivo assessment of antidiabetic and antioxidative activity of natural phytochemical isolated from fruit-pulp of Eugenia jambolana in streptozotocin induced diabetic rats. AB - OBJECTIVES: Eugenia jambolana (E. jambolana) is well known for its antidiabetic potential. The aim of the present study was to investigate the antidiabetic and antioxidative effect of an active compound (FIIc) isolated from fruit-pulp of E. jambolana in streptozotocin (45 mg/kg body weight)-induced diabetic rats. METHODS: FIIc was isolated from the crude aqueous extract of fruit-pulp by ion exchange column chromatography and high-performance column chromatography. Detailed UV, NMR, and IR spectra suggested that FIIc is alpha-hydroxy succinamic acid. FIIc was orally administered to diabetic rats at a dose of 10, 15, and 20 mg/kg body weight (mg/kg bwt.) to determine its effective dose. Thereafter, effective dose was administered to 8 weeks to determine its antidiabetic and antioxidative activity by estimation of glycemic index, lipid profile, key enzymes of carbohydrate metabolism, and oxidative stress parameters. RESULTS: Administration of 15 mg/kg dose daily for 8 weeks led to significant (P < 0.001) fall in fasting blood glucose. Treatment with FIIc (15 mg/kg bwt.) showed significant improvement (P < 0.001) in all the biochemical parameters. DISCUSSION: The results demonstrate that FIIc possesses significant antidiabetic and antioxidative activity. PMID- 27654809 TI - Multimorbidity in the community-dwelling elderly in urban China. AB - OBJECTIVES: The primary objective of the study was to investigate the prevalence and patterns of multimorbidity in the community-dwelling elderly in urban China. METHODS: By a cluster random sampling method, 2452 persons aged 60 years and older were enrolled as the subjects in an urban community in Nanjing, China. Data on 13 chronic diseases were collected by interviews, physical check-ups and support by physicians. Factor analyses and the logistic regression models were performed to analyze the patterns of multimorbidity. RESULTS: The prevalence of multimorbidity was 49.4% in the community-dwelling elderly in urban China. The observed prevalence of 6 chronic disease pairs was higher than their expected prevalence, including hypertension and diabetes, hypertension and coronary heart disease, hypertension and dyslipidaemia, diabetes and cataract, diabetes and hearing disorder, hypertension and stroke. Three patterns were detected as follows: the first pattern with a prevalence of 9.5% covered degenerative diseases (hearing disorder, cataract, joint disease) and cancer; The second pattern with a prevalence of 1.7% was characterized by liver disease, lung disease, gastrointestinal disease; And the third pattern with a prevalence of 22.4% was characterized by cardiovascular diseases (dyslipidaemia, hypertension, coronary heart disease), metabolic diseases (diabetes) and kidney disease. Compared with <70 years, >=80 years were found as the risk factor of the prevalence of three patterns. CONCLUSION: A significant proportion of elderly populations was affected by multimorbidity in urban China. Specific patterns of multimorbidity were found at group level and the prevalence was associated with age. PMID- 27654811 TI - The goodness of ethics in research ethics review. PMID- 27654812 TI - Interleukin 1-Beta (IL-1beta) Production by Innate Cells Following TLR Stimulation Correlates With TB Recurrence in ART-Treated HIV-Infected Patients. AB - BACKGROUND: Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV coinfection because immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. METHODS: Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time points before TB recurrence were stimulated with ligands for Toll-like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multicolor flow cytometry and intracellular cytokine staining were used to detect IL-1beta, TNF-alpha, IL-12, and IP10 responses from monocytes and myeloid dendritic cells (mDCs). RESULTS: Elevated production of IL-1beta from monocytes following TLR-2, TLR-4, and TLR 7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1beta from both monocytes and mDCs following Bacillus Calmette Guerin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs, respectively). CONCLUSION: Production of IL-1beta by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB. PMID- 27654813 TI - Brief Report: Informing Strategies to Build PrEP Capacity Among San Francisco Bay Area Clinicians. AB - A large pool of clinicians are needed to meet the growing demand for HIV preexposure prophylaxis. We surveyed a mixed group of HIV specialists and nonspecialists in the San Francisco Bay Area to determine their attitudes toward and training needs regarding prescribing preexposure prophylaxis to persons at increased risk of HIV infection. Willingness to prescribe was associated with experience in caring for HIV-infected patients (adjusted odds ratio 4.76, 95% confidence interval: 1.43 to 15.76, P = 0.01). Desire for further training was associated with concerns about drug resistance (P = 0.04) and side effects (P = 0.04) and was more common among noninfectious disease specialists. Clinicians favored online and in-person training methods. PMID- 27654815 TI - Seizures in Children With Severe Traumatic Brain Injury. AB - OBJECTIVE: Traumatic brain injury causes substantial morbidity and mortality in children. Posttraumatic seizures may worsen outcomes after traumatic brain injury. Posttraumatic seizures risk factors are not completely understood. Our objective was to clarify posttraumatic seizures risk factors in a large cohort of children with severe traumatic brain injury. DESIGN: Retrospective cohort study of a probabilistically linked dataset from the National Trauma Data Bank and the Pediatric Health Information Systems database, 2007-2010. SETTING: Twenty-nine U.S. children's hospitals. PATIENTS: A total of 2,122 children (age, < 18 yr old at admission) with linked National Trauma Data Bank and Pediatric Health Information Systems records, severe (emergency department Glasgow Coma Scale, < 8) traumatic brain injury, hospital length of stay more than 24 hours, and nonmissing disposition. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcome was posttraumatic seizures, identified using validated International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Prespecified candidate predictors of posttraumatic seizures included age, injury mechanism, emergency department Glasgow Coma Scale, intracranial hemorrhage type, hypoxia, hypotension, and cardiac arrest. Posttraumatic seizures were diagnosed in 25.2% of children with severe traumatic brain injury. In those without abuse/assault or subdural hemorrhage, the posttraumatic seizures rate varied between 36.6% in those less than 2 years old and 16.4% in those 14-17 years old. Age, abusive mechanism, and subdural hemorrhage are each significant predictors of posttraumatic seizures. The risk of posttraumatic seizures has a complex relationship with these predictors. The estimated odds of posttraumatic seizures decrease with advancing age, odds ratio equal to 0.929 (0.905-0.954) per additional year of age with no abuse/assault and no subdural hemorrhage; odds ratio equal to 0.820 (0.730-0.922) per additional year of age when abuse and subdural hemorrhage are present. An infant with accidental traumatic brain injury and subdural hemorrhage has approximately the same estimated probability of posttraumatic seizures as an abused infant without subdural hemorrhage (47% [95% CI, 39-55%] vs 50% [95% CI, 41-58%]; p = 0.69). The triad of young age, injury by abuse/assault, and subdural hemorrhage confers the greatest estimated probability for posttraumatic seizures (60% [95% CI, 53-66%]). CONCLUSIONS: Posttraumatic seizures risk in children with severe traumatic brain injury is greatest with a triad of younger age, injury by abuse/assault, and subdural hemorrhage. However, posttraumatic seizures are common even in the absence of these factors. PMID- 27654817 TI - Overuse of Medical Imaging and Its Radiation Exposure: Who's Minding Our Children? PMID- 27654818 TI - Diagnosing Traumatic Encephalopathy Syndrome. PMID- 27654816 TI - Dexmedetomidine Use in Critically Ill Children With Acute Respiratory Failure. AB - OBJECTIVE: Care of critically ill children includes sedation but current therapies are suboptimal. To describe dexmedetomidine use in children supported on mechanical ventilation for acute respiratory failure. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. SETTING: Thirty-one PICUs. PATIENTS: Data from 2,449 children; 2 weeks to 17 years old. INTERVENTIONS: Sedation practices were unrestrained in the usual care arm. Patients were categorized as receiving dexmedetomidine as a primary sedative, secondary sedative, periextubation agent, or never prescribed. Dexmedetomidine exposure and sedation and clinical profiles are described. MEASUREMENTS AND MAIN RESULTS: Of 1,224 usual care patients, 596 (49%) received dexmedetomidine. Dexmedetomidine as a primary sedative patients (n = 138; 11%) were less critically ill (Pediatric Risk of Mortality III-12 score median, 6 [interquartile range, 3-11]) and when compared with all other cohorts, experienced more episodic agitation. In the intervention group, time in sedation target improved from 28% to 50% within 1 day of initiating dexmedetomidine as a primary sedative. Dexmedetomidine as a secondary sedative usual care patients (n = 280; 23%) included more children with severe pediatric acute respiratory distress syndrome or organ failure. Dexmedetomidine as a secondary sedative patients experienced more inadequate pain (22% vs 11%) and sedation (31% vs 16%) events. Dexmedetomidine as a periextubation agent patients (n = 178; 15%) were those known to not tolerate an awake, intubated state and experienced a shorter ventilator weaning process (2.1 vs 2.3 d). CONCLUSIONS: Our data support the use of dexmedetomidine as a primary agent in low criticality patients offering the benefit of rapid achievement of targeted sedation levels. Dexmedetomidine as a secondary agent does not appear to add benefit. The use of dexmedetomidine to facilitate extubation in children intolerant of an awake, intubated state may abbreviate ventilator weaning. These data support a broader armamentarium of pediatric critical care sedation. PMID- 27654819 TI - Peripheral use of detachable coils: expanding the boundaries of embolization. AB - Percutaneous embolization was introduced in the mid-'70s and is now an established therapeutic procedure in current medical practice. With the use of improved imaging techniques, smaller profile catheters and new tools, embolization boundaries are significantly expanded in the last decades. Detachable coils were initially introduced in neuroradiology and are now part of the everyday peripheral embolization armamentarium. Purpose of this review article is to present an overview of the expanded possibilities that this novel material is offering in the field of peripheral embolization procedures. PMID- 27654820 TI - Evaluation of a training program for medicines-oriented policymakers to use a database of systematic reviews. AB - BACKGROUND: Suboptimal prescribing and medications use is a problem for health systems globally. Systematic reviews are a comprehensive resource that can help guide evidence-informed decision-making and implementation of interventions addressing such issues; however, a barrier to the use of systematic reviews is their inaccessibility (due to both dispersion across journals and inaccessibility of content). Publicly available databases, such as Rx for Change, provide quick access to summaries of appraised systematic reviews of professional and consumer oriented interventions to improve prescribing behaviour and appropriate medication use, and may help maximise the use of evidence to inform decisions. The present study aims to evaluate a training program to improve attitudes towards, confidence in skills, intentions to use, and use of systematic review evidence contained within Rx for Change. METHODS: Guided by the Knowledge to Action framework, a training program with content customised to local provider and consumer contexts was developed with knowledge user input. The training program consisted of a 6 minute information video, a 1 hour workshop with hands on, interactive and didactic components, and two post-training reminders. Forty nine people from five medicines-focused organisations in Canada and Australia attended one of six workshops. Participants were surveyed immediately pre and post and 3 months after training to evaluate their attitudes towards, confidence in skills, intentions to use, and use of Rx for Change, and attitudes towards and confidence in skills for using evidence for decision-making. Analyses for differences for each of the outcomes at three time points (pre, post and 3 months after training) was performed using a random effects model. RESULTS: Immediately post-training, there were higher respondent attitudes towards Rx for Change (mean increase = 0.54 out of 5, 95% CI, 0.18-0.83, P < 0.005); intention to use Rx for Change (0.53, 95% CI, 0.21-0.86, P < 0.005); confidence in skills for using Rx for Change (2.08, 95% CI, 1.74-2.42, P < 0.005); and confidence in skills for using evidence in policy decision-making (0.50, 95% CI, 0.22-0.77, P < .005) compared to pre-training. Confidence in skills for using both Rx for Change and evidence were maintained 3 months after training (both P < 0.005). CONCLUSIONS: Participants of this training program reported sustained improvements in their confidence in skills for using evidence in policy decision-making. This may have important implications for uptake of systematic review evidence promoting improved prescribing and medication use. PMID- 27654821 TI - Metabolic pathways for lipid synthesis under nitrogen stress in Chlamydomonas and Nannochloropsis. AB - Microalgae are currently being considered as a clean, sustainable and renewable energy source. Enzymes that catalyse the metabolic pathways for biofuel production are specific and require strict regulation and co-ordination. Thorough knowledge of these key enzymes along with their regulatory molecules is essential to enable rational metabolic engineering, to drive the metabolic flux towards the desired metabolites of importance. This paper reviews two key enzymes that play their role in production of bio-oil: DGAT (acyl-CoA:diacylglycerol acyltransferase) and PDAT (phospholipid:diacylglycerol acyltransferase). It also deals with the transcription factors that control the enzymes while cell undergoes a metabolic shift under stress. The paper also discusses the association of other enzymes and pathways that provide substrates and precursors for oil accumulation. Finally a futuristic solution has been proposed about a synthetic algal cell platform that would be committed towards biofuel synthesis. PMID- 27654822 TI - Low temperature and Daphnia-associated infochemicals promote colony formation of Scenedesmus obliquus and its harvesting. AB - OBJECTIVE: To explore the combined effects of temperature and Daphnia-associated infochemicals on colony formation of Scenedesmus obliquus to faciliate harvesting the algal biomass. RESULTS: A three-parameter modified Gaussian model fitted the changes of the number of cells per particle in S. obliquus induced by Daphnia culture filtrate well under any temperature. Decreases in temperature enhanced the induced-colony formation of Scenedesmus. The maximum colony size at 15-25 degrees C was significantly larger than those at 30-35 degrees C. An additional 1 or 2 days at low temperature was needed to reach the maximum colony size, which indicates the best harvest time for algal biomass. CONCLUSION: Induced-colony formation of Scenedesmus by Daphnia culture filtrate at 15-25 degrees C is recommended to settle algal cells. This condition facilitates harvesting the biomass. PMID- 27654823 TI - Production of 10S-hydroxy-8(E)-octadecenoic acid from oleic acid by whole recombinant Escherichia coli cells expressing 10S-dioxygenase from Nostoc punctiforme PCC 73102 with the aid of a chaperone. AB - OBJECTIVE: To increase the production of 10S-hydroxy-8(E)-octadecenoic acid from oleic acid by whole recombinant Escherichia coli cells expressing Nostoc punctiforme 10S-dioxygenase with the aid of a chaperone. RESULTS: The optimal conditions for 10S-hydroxy-8(E)-octadecenoic acid production by recombinant cells co-expressing chaperone plasmid were pH 9, 35 degrees C, 15 % (v/v) dimethyl sulfoxide, 40 g cells l-1, and 10 g oleic acid l-1. Under these conditions, recombinant cells co-expressing chaperone plasmid produced 7.2 g 10S-hydroxy-8(E) octadecenoic acid l-1 within 30 min, with a conversion yield of 72 % (w/w) and a volumetric productivity of 14.4 g l-1 h-1. CONCLUSION: The activity of recombinant cells expressing 10S-dioxygenase was increased by 200 % with the aid of a chaperone, demonstrating the first biotechnological production of 10S hydroxy-8(E)-octadecenoic acid using recombinant cells expressing 10S dioxygenase. PMID- 27654824 TI - A novel method to harvest Chlorella sp. by co-flocculation/air flotation. AB - OBJECTIVES: To develop a more effective dissolved air flotation process for harvesting microalgae biomass, a co-flocculation/air flotation (CAF) system was developed that uses an ejector followed by a helix tube flocculation reactor (HTFR) as a co-flocculation device to harvest Chlorella sp. 64.01. RESULTS: The optimal size distribution of micro-bubbles and an air release efficiency of 96 % were obtained when the flow ratio of inlet fluid (raw water) to motive fluid (saturated water) of the ejector was 0.14. With a reaction time of 24 s in the HTFR, microalgae cells and micro-bubbles were well flocculated, and these aerated flocs caused a fast rising velocity (96 m/h) and high harvesting efficiency (94 %). CONCLUSIONS: In a CAF process, micro-bubbles can be encapsulated into microalgae flocs, which makes aerated flocs more stable. CAF is an effective approach to harvesting microalgae. PMID- 27654826 TI - [What is new in basal cell carcinoma?] AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in fair skinned individuals. Although lymph node or visceral metastases are observed in less than 0.5 % of all cases, BCC can have a fatal course due to its highly invasive growth pattern. OBJECTIVES: To provide a comprehensive update on diagnosis, treatment, and prevention of BCC. MATERIALS AND METHODS: We review the current literature and recommendations of the German guidelines on treatment and prevention of skin cancer. The most pertinent developments are summarized in this review article. RESULTS: The use of optical coherence tomography and reflectance confocal microscopy can significantly improve the diagnosis of BCC compared with clinical assessment and dermoscopy alone. Mohs micrographic surgery remains the therapeutic gold standard for tumors in the head and facial area and tumors with high-risk features. The application of imiquimod, 5-fluorouracil, or photodynamic therapy should be restricted to low-risk superficial tumors. Topical inhibitors of the sonic hedgehog (SHH) pathway are currently being evaluated in early clinical trials. In contrast, vismodegib and sonidegib have been approved for the systemic treatment of locally advanced and metastatic BCC with good response rates. The most common adverse events of both agents are muscle cramps, dysgeusia, diffuse alopecia, weight loss, and fatigue. In an Australian phase III trial, oral nicotinamide (vitamin B3) reduced the occurrence of new BCC by 20 % in skin cancer patients. CONCLUSIONS: Targeted therapy with SHH inhibitors has improved the prognosis of locally advanced and metastatic BCC, albeit at the cost of a significant number of adverse events. PMID- 27654825 TI - Comparison of a physical activity recall questionnaire with accelerometry in children and adolescents with obesity: a pilot study. AB - This study aimed to determine the validity of the Habitual Activity Estimation Scale (HAES) for assessing physical activity (PA) in children and adolescents with severe obesity. Data were obtained from participants (n = 17) in the High Impact Strategies Toward Overweight Reduction in Youth study at the Hospital for Sick Children in Toronto. Objective measurement of PA was recorded with accelerometers and interpreted using counts-per-minute (CPM) cut-points developed for children and adolescents. Self-report measurement of PA was collected using the HAES questionnaire. Pearson correlations revealed HAES significantly overestimated average daily duration of vigorous (+48 +/- 64 min, p < 0.001) and moderate-light activity (+114 +/- 129 min, p < 0.001) but not inactivity (+38 +/- 158 min, p = 0.17). This disagreement may be explained by increased perceived exertion in obese participants when performing PA. Thus, the HAES should not be used to assess PA in obese youth. Further work to validate accelerometer CPM cut points for obese children and adolescents calibrated to energy consumption and perceived exertion during PA in this group is warranted. PMID- 27654827 TI - [Risk characteristics and survival rates of malignant melanoma in Germany and the Netherlands]. AB - BACKGROUND: Mortality and lethality of malignant melanoma (MM) show marked variations throughout Europe, thereunder a higher risk within the Netherlands (NL) when compared to Germany (D). GOAL AND METHODS: Comparison of systems and exploration of possible causal factors that could explain the difference between D and NL. Comparative healthcare research analysis using published international literature, as well as publicly accessible databases, and a subsequent hypothesis generating analysis. RESULTS: The higher rate of excised MM less than 1 mm in diameter in D (65 % vs. 45 %) confirms the clinical reports of the cancer registries. The biological factors for the emergence of MM, such as skin type, do not seem to significantly differ from each other. Among the further potential predictors there are no relevant differences within, for example, geographical conditions and the qualifications of the treating physicians. Primary prevention has a longer continual tradition in D. Here, secondary prevention is characterized by population-based extensive screening, which does not occur within the NL. In addition, distinct differences are found regarding access to dermatologists. CONCLUSION: System access to a medical specialist and the prevention of skin cancer are currently the most distinctive potential determinants of more favorable MM survival rate in Germany. PMID- 27654828 TI - Effect of Systemic Lupus Erythematosus on the Risk of Incident Respiratory Failure: A National Cohort Study. AB - PURPOSE: We conducted a nationwide cohort study to investigate the relationship between systemic lupus erythematosus (SLE) and the risk of incident respiratory failure. METHODS: From the National Health Insurance Research Database, we identified 11 533 patients newly diagnosed with SLE and 46 132 controls without SLE who were randomly selected through frequency-matching according to age, sex, and index year. Both cohorts were followed until the end of 2011 to measure the incidence of incident respiratory failure, which was compared between the 2 cohorts through a Cox proportional hazards regression analysis. RESULTS: The adjusted hazard ratio (aHR) of incident respiratory failure was 5.80 (95% confidence interval [CI] = 5.15-6.52) for the SLE cohort after we adjusted for sex, age, and comorbidities. Both men (aHR = 3.44, 95% CI = 2.67-4.43) and women (aHR = 6.79, 95% CI = 5.93-7.77) had a significantly higher rate of incident respiratory failure in the SLE cohort than in the non-SLE cohort. Both men and women aged <35 years (aHR = 31.2, 95% CI = 21.6-45.2), 35-65 years; (aHR = 6.19, 95% CI = 5.09-7.54) and >=65 years (aHR = 2.35, 95% CI = 1.92-2.87) had a higher risk of incident respiratory failure in the SLE cohort. Moreover, the risk of incident respiratory failure was higher in the SLE cohort than the non-SLE cohort, for subjects with (aHR = 2.65, 95% CI = 2.22-3.15) or without (aHR = 9.08, 95% CI = 7.72-10.7) pre-existing comorbidities. In the SLE cohort, subjects with >24 outpatient visits and hospitalizations per year had a higher incident respiratory failure risk (aHR = 21.7, 95% CI = 18.0-26.1) compared with the non SLE cohort. CONCLUSION: Patients with SLE are associated with an increased risk of incident respiratory failure, regardless of their age, sex, and pre-existing comorbidities; especially medical services with higher frequency. PMID- 27654830 TI - Onset of medication efficacy in patients with overactive bladder: What should we tell them? PMID- 27654829 TI - Exploring the Biocompatibility of Zwitterionic Copolymers for Controlling Macrophage Phagocytosis of Bacteria. AB - This paper provides a biomaterial derived from zwitterionic polymer for controlling macrophage phagocytosis of bacteria. A series of zwitterionic copolymers, named DMAPS-co-AA, are synthesized with 3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) and acrylic acid (AA). The biocompatibility of DMAPS-co-AA copolymers can be adjusted by adjusting the DMAPS-content or pH value. As the DMAPS-content increases, the biocompatibility of zwitterionic copolymer increases. The zwitterionic copolymers with DMAPS content above 30 wt% have higher biocompatibility. Moreover, the biocompatibility also increases significantly as the pH increases from 3.4 to 7.2. By adjusting the pH above 5.8, the zwitterionic copolymer with lower DMAPS-content also shows higher biocompatibility. Importantly, after incubation with the DMAPS-co-AA copolymer solutions at different pH values, phagocytosis behavior of macrophage RAW264.7 cells can also be adjusted. The phagocytosis of bacteria is enhanced at pH = 7.2. Thus, it is proposed that zwitterionic copolymers can be used for controlling phagocytosis of bacteria. PMID- 27654832 TI - Pneumococcal vaccines for cystic fibrosis. AB - BACKGROUND: Invasive pneumococcal disease is associated with significant mortality and many countries have introduced routine pneumococcal vaccination into their childhood immunisation programmes. Whilst pneumococcal disease in cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection against pulmonary exacerbations caused by this pathogen. In the USA and UK pneumococcal vaccination is currently recommended for all children and adults with cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To assess the efficacy of pneumococcal vaccines in reducing morbidity in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, the pharmaceutical manufacturers of the polysaccharide and conjugate pneumococcal vaccines were approached.Date of the most recent search: 27 June 2016. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing pneumococcal vaccination (with either a polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo in children or adults with cystic fibrosis were eligible for inclusion. DATA COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: There are no trials included in this review. AUTHORS' CONCLUSIONS: As no trials were identified we cannot draw conclusions on the efficacy of routine pneumococcal immunisation in people with cystic fibrosis in reducing their morbidity or mortality. As many countries now include pneumococcal immunisation in their routine childhood vaccination schedule it is unlikely that future randomised controlled trials will be initiated. Rigorously conducted epidemiological studies may offer the opportunity to evaluate the efficacy of pneumococcal vaccination in reducing morbidity and mortality in people with cystic fibrosis. PMID- 27654831 TI - Functional Neuroimaging in Migraine: Chances and Challenges. AB - Functional neuroimaging studies are an indispensable tool in headache research and have greatly contributed to our understanding of migraine pathophysiology. The past two decades have identified the brainstem as the target region of interest in migraine pathophysiology: Recent evidence suggests that certain areas of the central nervous system and especially the brainstem periodically change activity during different stages of the migraine cycle. Additionally, the number of resting-state functional MRI studies in migraine has increased greatly in recent years. Three future trends in migraine neuroimaging can be identified: brainstem optimized functional imaging, longitudinal approaches tracking biological changes through the migraine cycle, and optimized resting-state fMRI. Consequently, we face a lot of difficulties regarding image noise and artifacts, organizational details, and data interpretation. Optimized neuroimaging studies and new approaches will continue to greatly contribute to our pathophysiological understanding of migraine. PMID- 27654834 TI - Low-Frequency Intracortical Electrical Stimulation Decreases Sensorimotor Cortex Hyperexcitability in the Acute Phase of Ischemic Stroke. AB - Ischemic stroke causes a series of complex pathophysiological events in the brain. Electrical stimulation of the brain has been considered as a novel neuroprotection intervention to save the penumbra. However, the effect on the cells' responsiveness and their ability to survive has yet to be established. The objective of the present study was to investigate the effects of low-frequency intracortical electrical stimulation (lf-ICES) applied to the ischemia-affected sensorimotor cortex immediately following ischemic stroke. Twenty male Sprague Dawley rats were instrumented with an intracortical microelectrode array (IC MEA) and a cuff-electrode around the sciatic nerve. Photothrombosis intervention was performed within the sensorimotor cortex and the electrophysiological changes were assessed by analysis of the neural responses to stimulation of the sciatic nerve. Neuroprotection intervention consisted of eight 23 min lf-ICES blocks applied to the IC MEA during the initial 4 h following photothrombosis. Our results revealed that the area and magnitude of the sensorimotor cortex response significantly increased if ischemic stroke was allowed to progress uninterrupted, whereas this was not observed for the group of rats subjected to lf-ICES. Our findings indicate that low-frequency electrical stimulation is able to minimize hyperexcitability and may therefore be a candidate as neuroprotection intervention in the future. PMID- 27654835 TI - A Masked Phosphinidene Trapped in a Fluxional NCN Pincer. AB - The trapping of a phosphinidene (R-P) in an NCN pincer is presented. Stabilized phosphinidene 1 was characterized by 31 P{1 H}, 1 H, and 13 C{1 H} NMR spectroscopy, exhibiting an averaged C2v symmetry in solution between -60 and 60 degrees C. In the solid state, the phosphinidene is coordinated by one adjacent N atom featuring a formal P-N bond (1.757(2) A) to give a five-membered ring with some aromatic character, confirmed by DFT calculations (B3LYP-D3/6-311G**++) to be the ground-state structure. Equilibration of the two N ligands occurs rapidly in solution via a "bell-clapper"-type process through an associative symmetric transition state calculated to lie 4.0 kcal mol-1 above the ground state. PMID- 27654836 TI - Religiousness and Mental Health: Systematic Review Study. AB - Many people use religious beliefs and practices to cope with stressful life events and derive peace of mind and purpose in life. The goal of this paper was to systematically review the recent psychological literature to assess the role of religion in mental health outcomes. A comprehensive literature search was conducted using medical and psychological databases on the relationship between religiosity and mental health. Seventy-four articles in the English and Arabic languages published between January 2000 and March 2012 were chosen. Despite the controversial relationship between religion and psychiatry, psychology, and medical care, there has been an increasing interest in the role which spirituality and religion play in mental health. The findings of past research showed that religion could play an important role in many situations, as religious convictions and rules influence the believer's life and health care. Most of the past literature in this area reported that there is a significant connection between religious beliefs and practices and mental health. PMID- 27654837 TI - Short-term efficacy and safety of ranibizumab for macular oedema secondary to retinal vein occlusion in Japanese patients. AB - PURPOSE: To evaluate the efficacy and safety of ranibizumab 0.5 mg in Japanese patients with visual impairment due to macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) and to support the applicability of the phase III results from Caucasian to Japanese populations. METHODS: This is a 3-month, open-label, single-arm, multicentre, phase III study. Thirty-one patients (15 BRVO and 16 CRVO) aged >=18 years with a best-corrected visual acuity (BCVA) letter score of 19-73 (BRVO) or 24-73 (CRVO) were included. The primary end-point was the mean average change in BCVA from baseline to month 1 through month 3 after three consecutive monthly intravitreal injections of ranibizumab 0.5 mg. Secondary end-points were mean change in BCVA and central subfield thickness (CSFT), categorized BCVA, and safety over 3 months. RESULTS: At month 3, the mean average change in BCVA improved substantially from baseline for BRVO (11.3 letters, p = 0.001) and CRVO (6.7 letters, p = 0.019). The mean BCVA improved (12.8 and 9.1 letters) and the mean CSFT decreased (212.5 and 442.1 MUm) from baseline to month 3. At month 3, 26.7% (BRVO) and 31.3% (CRVO) of the patients had a gain of >=15 letters from baseline. Safety findings in this study were similar to those reported in the previous clinical trials. CONCLUSION: Ranibizumab was effective in improving BCVA and was well tolerated in Japanese patients with BRVO and CRVO. The findings from this study were consistent with those reported in the Caucasian population. PMID- 27654838 TI - 1 H NMR study and multivariate data analysis of reindeer skin tanning methods. AB - Reindeer skin clothing has been an essential component in the lives of indigenous people of the arctic and sub-arctic regions, keeping them warm during harsh winters. However, the skin processing technology, which often conveys the history and tradition of the indigenous group, has not been well documented. In this study, NMR spectra and relaxation behaviors of reindeer skin samples treated with a variety of vegetable tannin extracts, oils and fatty substances are studied and compared. With the assistance of principal component analysis (PCA), one can recognize patterns and identify groupings of differently treated samples. These methods could be important aids in efforts to conserve museum leather artifacts with unknown treatment methods and in the analysis of reindeer skin tanning processes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27654839 TI - Hemorrhagic and Thromboembolic Complications after Hepato-Biliary-Pancreatic Surgery in Patients Receiving Antithrombotic Therapy. AB - BACKGROUND: Perioperative management for patients receiving long-term anticoagulant (AC) and antiplatelet (AP) therapy is a great concern for surgeons. This single-center retrospective study evaluated the risks of hemorrhage and thromboembolism after hepato-biliary-pancreatic (HBP) surgery in such patients. METHODS: Between 2009 and 2014, 886 patients underwent HBP surgery. Patients were categorized into the AC (n = 39), AP (n = 77), or control (n = 770) group according to the administration of antithrombotic drugs. Perioperative management of AC and AP therapies followed the guidelines of the Japanese Circulation Society. The incidences of hemorrhage and thromboembolism were compared among groups. We used 1:1 propensity score matching and compared the incidences between the matched pairs. RESULTS: There were 0, 1 (1.3%), and 26 (3.4%) hemorrhagic complications in the AC, AP, and control groups, respectively (p = 0.16). There were 0, 1 (1.3%), and 6 (0.8%) thromboembolic complications in the AC, AP, and control groups, respectively (p = 0.66). There was no significant difference in hemorrhagic and thromboembolic complications between the propensity-matched pairs. CONCLUSION: The incidences of hemorrhage and thromboembolism after HBP surgery in patients receiving long-term AC and AP therapies are within acceptable ranges. PMID- 27654840 TI - AP-SKAT: highly-efficient genome-wide rare variant association test. AB - BACKGROUND: Genome-wide association studies have revealed associations between single-nucleotide polymorphisms (SNPs) and phenotypes such as disease symptoms and drug tolerance. To address the small sample size for rare variants, association studies tend to group gene or pathway level variants and evaluate the effect on the set of variants. One of such strategies, known as the sequential kernel association test (SKAT), is a widely used collapsing method. However, the reported p-values from SKAT tend to be biased because the asymptotic property of the statistic is used to calculate the p-value. Although this bias can be corrected by applying permutation procedures for the test statistics, the computational cost of obtaining p-values with high resolution is prohibitive. RESULTS: To address this problem, we devise an adaptive SKAT procedure termed AP SKAT that efficiently classifies significant SNP sets and ranks them according to the permuted p-values. Our procedure adaptively stops the permutation test when the significance level is outside some confidence interval of the estimated p value for a binomial distribution. To evaluate the performance, we first compare the power and sample size calculation and the type I error rates estimate of SKAT, SKAT-O, and the proposed procedure using genotype data in the SKAT R package and from 1000 Genome Project. Through computational experiments using whole genome sequencing and SNP array data, we show that our proposed procedure is highly efficient and has comparable accuracy to the standard procedure. CONCLUSIONS: For several types of genetic data, the developed procedure could achieve competitive power and sample size under small and large sample size conditions with controlling considerable type I error rates, and estimate p values of significant SNP sets that are consistent with those estimated by the standard permutation test within a realistic time. This demonstrates that the procedure is sufficiently powerful for recent whole genome sequencing and SNP array data with increasing numbers of phenotypes. Additionally, this procedure can be used in other association tests by employing alternative methods to calculate the statistics. PMID- 27654841 TI - Hospital Readmissions Reduction Program: Safety-Net Hospitals Show Improvement, Modifications To Penalty Formula Still Needed. AB - Many observers are calling for modification of Medicare's Hospital Readmissions Reduction Program (HRRP) to relieve an unfair burden on safety-net hospitals, which serve low-income populations and consequently have relatively high readmission rates. To broaden the perspective on this issue, we addressed the fundamental question of whether the HRRP has been an effective tool for reducing thirty-day readmissions in safety-net hospitals. In the first three years of the program, these hospitals reduced readmissions for heart attack by 2.86 percentage points, heart failure by 2.78 percentage points, and pneumonia by 1.77 percentage points, and they also reduced the disparity between their readmission rates and those of other hospitals. While the fairness issue remains unresolved, it appears that safety-net hospitals have been able to respond to HRRP incentives. PMID- 27654842 TI - The health care experience of patients with cancer during the last year of life: Analysis of the SEER-CAHPS data set. AB - BACKGROUND: Providing high-quality medical care for individuals with cancer during their last year of life involves a range of challenges. An important component of high-quality care during this critical period is ensuring optimal patient satisfaction. The objective of the current study was to assess factors influencing health care ratings among individuals with cancer within 1 year before death. METHODS: The current study used the Surveillance, Epidemiology, and End Results (SEER)-Consumer Assessment of Healthcare Providers and Systems (CAHPS) data set, a new data resource linking patient-reported information from the CAHPS Medicare Survey with clinical information from the National Cancer Institute's SEER program. The study included 5102 Medicare beneficiaries diagnosed with cancer who completed CAHPS between 1998 and 2011 within 1 year before their death. Multivariable logistic regression analyses examined associations between patient demographic and insurance characteristics with 9 measures of health care experience. RESULTS: Patients with higher general or mental health status were significantly more likely to indicate excellent experience with nearly all measures examined. Sex, race/ethnicity, and education also were found to be significant predictors for certain ratings. Greater time before death predicted an increased likelihood of higher ratings for health plan and specialist physician. Clinical characteristics were found to have few significant associations with experience of care. Individuals in fee-for-service Medicare plans (vs Medicare Advantage) had a greater likelihood of excellent experience with health plans, getting care quickly, and getting needed care. CONCLUSIONS: Among patients with cancer within 1 year before death, experience with health plans, physicians, and medical care were found to be associated with sociodemographic, insurance, and clinical characteristics. These findings provide guidance for the development of programs to improve the experience of care among individuals with cancer. Cancer 2017;123:336-344. (c) 2016 American Cancer Society. PMID- 27654843 TI - Reinventing HCV Treatment: Past and Future Perspectives. AB - This review paper summarizes the epidemiology of hepatitis C virus (HCV) and chronic HCV infection, including HCV virology and treatment regimens. Specifically, we focus on the evolution of past, current, and future HCV treatment options, the reasons for treatment failure, and the impact of resistance-associated variants on treatment success. PMID- 27654844 TI - Redox Non-Innocent Behavior of a Terminal Iridium Hydrazido(2-) Triple Bond. AB - The synthesis of the first terminal Group 9 hydrazido(2-) complex, Cp*IrN(TMP) (6) (TMP=2,2,6,6-tetramethylpiperidine) is reported. Electronic structure and X ray diffraction analysis indicate that this complex contains an Ir-N triple bond, similar to Bergman's seminal Cp*Ir(Nt Bu) imido complex. However, in sharp contrast to Bergman's imido, 6 displays remarkable redox non-innocent reactivity owing to the presence of the Nbeta lone pair. Treatment of 6 with MeI results in electron transfer from Nbeta to Ir prior to oxidative addition of MeI to the iridium center. This behavior opens the possibility of carrying out facile oxidative reactions at a formally IrIII metal center through a hydrazido(2 )/isodiazene valence tautomerization. PMID- 27654845 TI - Psychosocial therapy and causes of death after deliberate self-harm: a register based, nationwide multicentre study using propensity score matching. AB - BACKGROUND: Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death. METHOD: In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow up period. RESULTS: At the end of follow-up, 391 (6.9%) of 5678 patients in the psychosocial therapy group had died, compared with 1736 (10.2%) of 17 034 patients in the matched comparison group. Lower odds ratios of dying by mental or behavioural disorders [0.54, 95% confidence interval (CI) 0.37-0.79], alcohol related causes (0.63, 95% CI 0.50-0.80) and other diseases and medical conditions (0.61, 95% CI 0.49-0.77) were noted in the psychosocial therapy group. Also, we found a reduced risk of dying by suicide as well as other external causes, however, not by neoplasms and circulatory system diseases. Numbers needed to treat were 212.9 (95% CI 139.5-448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2-210.5) for alcohol-related causes and 96.8 (95% CI 69.1-161.8) for other diseases and medical conditions. CONCLUSIONS: Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death from select medical conditions and external causes. These promising results should be tested in a randomized design. PMID- 27654846 TI - Brevibacterium sediminis sp. nov., isolated from deep-sea sediments from the Carlsberg and Southwest Indian Ridges. AB - Three actinobacterial strains, FXJ8.128, FXJ8.269T and FXJ8.309, were isolated from deep-sea sediments collected from the Carlsberg Ridge and Southwest Indian Ridge at depths of 3690, 1800 and 2461 m, respectively. The three strains had highly similar 16S rRNA gene sequences (99.8-99.9 % identities) and formed a monophyletic clade within the Brevibacterium 16S rRNA gene tree, showing 98.2 98.9 % 16S rRNA gene sequence identities with type strains Brevibacterium epidermidis NCIMB 702286T, Brevibacterium iodinum DSM 20626T, Brevibacterium linens DSM 20425T, Brevibacterium oceani BBH7T and Brevibacterium permense VKM Ac 2280T. All three isolates showed activity towards the breakdown of pectin and fluoranthene. They contained MK-8(H2) as the most predominant menaquinone, diphosphatidylglycerol, phosphatidylglycerol and a glycolipd as the main polar lipids, and anteiso-C15 : 0 and anteiso-C17 : 0 as the major cellular fatty acids. Moreover, the three isolates were distinguished readily from the phylogenetically related type strains by DNA-DNA hybridization values, by random amplified polymorphic DNA fingerprint profiles and by a range of physiological and biochemical characteristics. On the basis of the above polyphasic taxonomic data, strains FXJ8.128, FXJ8.269T and FXJ8.309 represent a novel species of the genus Brevibacterium, for which the name Brevibacterium sediminis sp. nov. is proposed. The type strain is FXJ8.269T (=CGMCC 1.15472T=DSM 102229T). PMID- 27654847 TI - Cyclone Aila, livelihood stress, and migration: empirical evidence from coastal Bangladesh. AB - This paper investigates why households migrated as a unit to Khulna City from the affected Upazilas of Dacope and Koyra in Khulna District, Bangladesh, following Cyclone Aila on 25 May 2009. The study reveals that households migrated primarily because of the livelihood stress that resulted from the failure to derive a secure income like before the event from the impacted areas-other push and pull factors also played a part in their migration decision. Despite all of the Aila induced losses and problems, all households wanted to avoid migration, but they were unable to do so for this principal reason. The findings also demonstrate that, if livelihoods cannot be restored, some form of widespread migration is inevitable after a disaster such as this one. In addition, they show that migration has the potential to serve as a key adaptive response to environmental events, as evidenced by the improved economic conditions of a substantial number of the migrated households. PMID- 27654849 TI - Surgical abdomen with intestinal pseudo-obstruction as presenting feature of atypical Kawasaki disease. PMID- 27654848 TI - A hypo-status in drug-dependent brain revealed by multi-modal MRI. AB - Drug addiction is a chronic brain disorder with no proven effective cure. Assessing both structural and functional brain alterations by using multi-modal, rather than purely unimodal imaging techniques, may provide a more comprehensive understanding of the brain mechanisms underlying addiction, which in turn may facilitate future treatment strategies. However, this type of research remains scarce in the literature. We acquired multi-modal magnetic resonance imaging from 20 cocaine-addicted individuals and 19 age-matched controls. Compared with controls, cocaine addicts showed a multi-modal hypo-status with (1) decreased brain tissue volume in the medial and lateral orbitofrontal cortex (OFC); (2) hypo-perfusion in the prefrontal cortex, anterior cingulate cortex, insula, right temporal cortex and dorsolateral prefrontal cortex and (3) reduced irregularity of resting state activity in the OFC and limbic areas, as well as the cingulate, visual and parietal cortices. In the cocaine-addicted brain, larger tissue volume in the medial OFC, anterior cingulate cortex and ventral striatum and smaller insular tissue volume were associated with higher cocaine dependence levels. Decreased perfusion in the amygdala and insula was also correlated with higher cocaine dependence levels. Tissue volume, perfusion, and brain entropy in the insula and prefrontal cortex, all showed a trend of negative correlation with drug craving scores. The three modalities showed voxel-wise correlation in various brain regions, and combining them improved patient versus control brain classification accuracy. These results, for the first time, demonstrate a comprehensive cocaine-dependence and craving-related hypo-status regarding the tissue volume, perfusion and resting brain irregularity in the cocaine-addicted brain. PMID- 27654851 TI - A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high intermediate risk diffuse large B-cell lymphoma. PMID- 27654850 TI - Species From Feces: Order-Wide Identification of Chiroptera From Guano and Other Non-Invasive Genetic Samples. AB - Bat guano is a relatively untapped reservoir of information, having great utility as a DNA source because it is often available at roosts even when bats are not and is an easy type of sample to collect from a difficult-to-study mammalian order. Recent advances from microbial community studies in primer design, sequencing, and analysis enable fast, accurate, and cost-effective species identification. Here, we borrow from this discipline to develop an order-wide DNA mini-barcode assay (Species from Feces) based on a segment of the mitochondrial gene cytochrome c oxidase I (COI). The assay works effectively with fecal DNA and is conveniently transferable to low-cost, high-throughput Illumina MiSeq technology that also allows simultaneous pairing with other markers. Our PCR primers target a region of COI that is highly discriminatory among Chiroptera (92% species-level identification of barcoded species), and are sufficiently degenerate to allow hybridization across diverse bat taxa. We successfully validated our system with 54 bat species across both suborders. Despite abundant arthropod prey DNA in guano, our primers were highly specific to bats; no arthropod DNA was detected in thousands of feces run on Sanger and Illumina platforms. The assay is extendable to fecal pellets of unknown age as well as individual and pooled guano, to allow for individual (using singular fecal pellets) and community (using combined pellets collected from across long-term roost sites) analyses. We developed a searchable database (http://nau.edu/CEFNS/Forestry/Research/Bats/Search-Tool/) that allows users to determine the discriminatory capability of our markers for bat species of interest. Our assay has applications worldwide for examining disease impacts on vulnerable species, determining species assemblages within roosts, and assessing the presence of bat species that are vulnerable or facing extinction. The development and analytical pathways are rapid, reliable, and inexpensive, and can be applied to ecology and conservation studies of other taxa. PMID- 27654853 TI - Tolvaptan in Acute Heart Failure: Time to Move On. PMID- 27654852 TI - PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. AB - PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1 specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients. PMID- 27654854 TI - Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure. AB - BACKGROUND: The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overload, potentially facilitating decongestion and improving the clinical course of patients with acute heart failure (AHF). OBJECTIVES: The TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conducted to address the acute use of tolvaptan to improve congestion in AHF. METHODS: The TACTICS-HF study randomized patients (n = 257) within 24 h of AHF presentation in a prospective, double blind, placebo-controlled trial. Patients were eligible regardless of ejection fraction, and were randomized to either 30 mg of tolvaptan or placebo given at 0, 24, and 48 h, with a fixed-dose furosemide regimen as background therapy. The primary endpoint was the proportion of patients considered responders at 24 h. Secondary endpoints included symptom improvement, changes in renal function, and clinical events. RESULTS: Dyspnea relief by Likert scale was similar between groups at 8 h (25% moderately or markedly improved with tolvaptan vs. 28% placebo; p = 0.59) and at 24 h (50% tolvaptan vs. 47% placebo; p = 0.80). Need for rescue therapy was also similar at 24 h (21% tolvaptan, 18% placebo; p = 0.57). The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32). Tolvaptan resulted in greater weight loss and net fluid loss compared with placebo, but tolvaptan-treated patients were more likely to experience worsening renal function during treatment. There were no differences in in-hospital or post-discharge clinical outcomes. CONCLUSIONS: In patients hospitalized with AHF, dyspnea, and congestion, the addition of tolvaptan to a standardized furosemide regimen did not improve the number of responders at 24 h, despite greater weight loss and fluid loss. (Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure [TACTICS-HF]; NCT01644331). PMID- 27654855 TI - Dysregulated JAK2 expression by TrkC promotes metastasis potential, and EMT program of metastatic breast cancer. AB - Metastatic breast cancers are aggressive tumors associated with high levels of epithelial-mesenchymal transition (EMT) markers, activation of IL6/JAK2/STAT3 and PI3K/AKT pathways for cell growth, mobility, invasion, metastasis, and CSC status. We identified a new molecular and functional network present in metastasis that regulates and coordinates with TrkC. Inhibition of SOCS3-mediated JAK2 degradation by TrkC increases total JAK2/STAT3 expression, and then leads to upregulation of Twist-1 through activation of JAK2/STAT3 cascade. Also, TrkC increases secretion and expression of IL-6, suggesting that this autocrine loop generated by TrkC maintains the mesenchymal state by continued activation of the JAK2/STAT3 cascade and upregulation of Twist expression. Moreover, TrkC interacts with the c-Src/Jak2 complex, which increases Twist-1 and Twist-2 levels via regulation of JAK2/STAT3 activation and JAK2/STAT3 expression. Furthermore, TrkC enhances metastatic potential of breast cancer via induction of EMT by upregulating Twist-1 and Twist-2. Additionally, TrkC significantly enhances the ability of breast cancer cells to form pulmonary metastases and primary tumor formation. Unexpectedly, we found that TrkC expression and clinical breast tumor pathological phenotypes show significant correlation. These findings suggest that TrkC plays a central role in tumorigenicity, metastasis, and self-renewal traits of metastatic breast cancer. PMID- 27654856 TI - Mitochondrial pathogenic mechanism and degradation in optineurin E50K mutation mediated retinal ganglion cell degeneration. AB - Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K-tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress. PMID- 27654857 TI - Giving formulary and drug cost information to providers and impact on medication cost and use: a longitudinal non-randomized study. AB - BACKGROUND: Providers wish to help patients with prescription costs but often lack drug cost information. We examined whether giving providers formulary and drug cost information was associated with changes in their diabetes patients' drug costs and use. We conducted a longitudinal non-randomized evaluation of the web-based Prescribing Guide ( www.PrescribingGuide.com ), a free resource available to Hawaii's providers since 2006, which summarizes the formularies and copayments of six health plans for drugs to treat 16 common health conditions. All adult primary care physicians in Hawaii were offered the Prescribing Guide, and providers who enrolled received a link to the website and regular hardcopy updates. METHODS: We analyzed prescription claims from a large health plan in Hawaii for 5,883 members with diabetes from 2007 (baseline) to 2009 (follow-up). Patients were linked to 299 "main prescribing" providers, who on average, accounted for >88 % of patients' prescriptions and drug costs. We compared changes in drug costs and use for "study" patients whose main provider enrolled to receive the Prescribing Guide, versus "control" patients whose main provider did not enroll to receive the Prescribing Guide. RESULTS: In multivariate analyses controlling for provider specialty and clustering of patients by providers, both patient groups experienced similar increases in number of prescriptions (+3.2 vs. +2.7 increase, p = 0.24), and days supply of medications (+141 vs. +129 increase, p = 0.40) averaged across all drugs. Total and out-of pocket drug costs also increased for both control and study patients. However, control patients showed higher increases in yearly total drug costs of $208 per patient (+$792 vs. +$584 increase, p = 0.02) and in 30-day supply costs (+$9.40 vs. +$6.08 increase, p = 0.03). Both groups experienced similar changes in yearly out-of-pocket costs (+$41 vs + $31 increase, p = 0.36) and per 30-day supply ( $0.23 vs. -$0.19 decrease, p = 0.996). CONCLUSION: Giving formulary and drug cost information to providers was associated with lower increases in total drug costs but not with lower out-of-pocket costs or greater medication use. Insurers and health information technology businesses should continue to increase providers' access to formulary and drug cost information at the point of care. PMID- 27654858 TI - Utilization of paramagnetic relaxation enhancements for structural analysis of actin-binding proteins in complex with actin. AB - Actin cytoskeleton dynamics are controlled by various actin binding proteins (ABPs) that modulate the polymerization of the monomeric G-actin and the depolymerization of filamentous F-actin. Although revealing the structures of the actin/ABP complexes is crucial to understand how the ABPs regulate actin dynamics, the X-ray crystallography and cryoEM methods are inadequate to apply for the ABPs that interact with G- or F-actin with lower affinity or multiple binding modes. In this study, we aimed to establish the alternative method to build a structural model of G-actin/ABP complexes, utilizing the paramagnetic relaxation enhancement (PRE) experiments. Thymosin beta4 (Tbeta4) was used as a test case for validation, since its structure in complex with G-actin was reported recently. Recombinantly expressed G-actin, containing a cysteine mutation, was conjugated with a nitroxyl spin label at the specific site. Based on the intensity ratio of the 1H-15N HSQC spectra of Tbeta4 in the complex with G actin in the paramagnetic and diamagnetic states, the distances between the amide groups of Tbeta4 and the spin label of G-actin were estimated. Using the PRE derived distance constraints, we were able to compute a well-converged docking structure of the G-actin/Tbeta4 complex that shows great accordance with the reference structure. PMID- 27654860 TI - Neuronal development: Signalling synaptogenesis. PMID- 27654859 TI - Mammographic density and breast cancer risk: a mediation analysis. AB - BACKGROUND: High mammographic density (MD) is a strong risk factor for breast cancer. However, it is unclear whether high MD is an intermediate phenotype or whether breast cancer risk factors influence breast cancer risk and MD independently. METHODS: Our study population included 1290 invasive breast cancer cases and 3422 controls from the Nurses' Health Studies. We estimated the percent of the total association between the risk factor and breast cancer that was mediated by MD. RESULTS: In both pre- and postmenopausal women, the association between history of biopsy-confirmed benign breast disease and risk was partially mediated by percent MD (percent mediated (PM) = 17 %, p < 0.01 and PM = 33 %, p = 0.04, respectively). In premenopausal women, the associations between early life body size (adolescent somatotype and BMI at age 18) and breast cancer risk were substantially mediated by percent MD (PM = 73 %, p = 0.05 and PM = 82 %, p = 0.04, respectively). In postmenopausal women, the proportion of the associations of childhood somatotype and adolescent somatotype that were mediated by percent MD were lower (PM = 26 %, p = 0.01 for both measures). Hormone therapy use at mammogram was significantly mediated by percent MD in postmenopausal women (PM = 22 %, p < 0.01). Associations with other risk factors, such as age at menarche or family history of breast cancer, were not mediated by percent MD. CONCLUSIONS: Percent MD partially mediated some of the associations between risk factors and breast cancer, though the magnitude varied by risk factor and menopausal status. These findings suggest that high MD may be an intermediate in some biological pathways for breast cancer development. PMID- 27654861 TI - Adult neurogenesis: Encouraging integration. PMID- 27654864 TI - New way to define disease is needed to reduce overdiagnosis, experts agree. PMID- 27654863 TI - Synergy of Microfluidics and Ultrasound : Process Intensification Challenges and Opportunities. AB - A compact snapshot of the current convergence of novel developments relevant to chemical engineering is given. Process intensification concepts are analysed through the lens of microfluidics and sonochemistry. Economical drivers and their influence on scientific activities are mentioned, including innovation opportunities towards deployment into society. We focus on the control of cavitation as a means to improve the energy efficiency of sonochemical reactors, as well as in the solids handling with ultrasound; both are considered the most difficult hurdles for its adoption in a practical and industrial sense. Particular examples for microfluidic clogging prevention, numbering-up and scaling-up strategies are given. To conclude, an outlook of possible new directions of this active and promising combination of technologies is hinted. PMID- 27654865 TI - Novel and Practical Scoring Systems for the Diagnosis of Thyroid Nodules. AB - OBJECTIVE: The clinical management of patients with thyroid nodules that are biopsied by fine-needle aspiration cytology and yield indeterminate results remains unsettled. The BRAF V600E mutation has dubious diagnostic value due to its low sensitivity. Novel strategies are urgently needed to distinguish thyroid malignancies from thyroid nodules. DESIGN: This prospective study included 504 thyroid nodules diagnosed by ultrasonography from 468 patients, and fine-needle aspiration cytology was performed under ultrasound guidance. Cytology and molecular analysis, including BRAF V600E, RET/PTC1 and RET/PTC3, were conducted simultaneously. The cytology, ultrasonography results, and mutational status were gathered and analyzed together. Predictive scoring systems were designed using a combination of diagnostic parameters for ultrasonography, cytology and genetic analysis. The utility of the scoring systems was analyzed and compared to detection using the individual methods alone or combined. RESULT: The sensitivity of scoring systema (ultrasonography, cytology, BRAF V600E, RET/PTC) was nearly identical to that of scoring systemb (ultrasonography, cytology, BRAF V600E); these were 91.0% and 90.2%, respectively. These sensitivities were significantly higher than those obtained using FNAC, genetic analysis and US alone or combined; their sensitivities were 63.9%, 70.7% and 87.2%, respectively. Scoring systemc (ultrasonography, cytology) was slightly inferior to the former two scoring systems but still had relatively high sensitivity and specificity (80.5% and 95.1%, respectively), which were significantly superior to those of single cytology, ultrasonography or genetic analysis. In nodules with uncertainty cytology, scoring systema, scoring systemb and scoring systemc could elevate the malignancy detection rates to 69.7%, 69.7% and 63.6%, respectively. CONCLUSION: These three scoring systems were quick for clinicians to master and could provide quantified information to predict the probability of malignant nodules. Scoring systemb is recommended for improving the detection rate among nodules of uncertain cytology. PMID- 27654862 TI - Mind-wandering as spontaneous thought: a dynamic framework. AB - Most research on mind-wandering has characterized it as a mental state with contents that are task unrelated or stimulus independent. However, the dynamics of mind-wandering - how mental states change over time - have remained largely neglected. Here, we introduce a dynamic framework for understanding mind wandering and its relationship to the recruitment of large-scale brain networks. We propose that mind-wandering is best understood as a member of a family of spontaneous-thought phenomena that also includes creative thought and dreaming. This dynamic framework can shed new light on mental disorders that are marked by alterations in spontaneous thought, including depression, anxiety and attention deficit hyperactivity disorder. PMID- 27654867 TI - Review of Recent Large-Scale Burn Disasters Worldwide in Comparison to Preparedness Guidelines. AB - The US National Bioterrorism Hospital Preparedness Program indicates that each care facility must have "a plan to care for at least 50 cases per million people for patients suffering burns or trauma" to receive national funding disaster preparedness. The purpose of this study is to evaluate whether this directive is commensurate with the severity recent burn disasters, both nationally and internationally. We conducted a review of medical journal articles, investigative fire reports, and media news sources for major burn disasters dating from 1990 to present day. We defined a major burn disaster as any incident with >=50 burn injuries and/or >= 30 burn-related deaths. We compared existing preparedness guidelines with the magnitude of recent burn disasters using as reference the 2005 U.S. Health and Human Services directive that each locale must "have a plan to care for at least 50 cases per million people for patients suffering burns or trauma." We reported the number of actual casualties for each incident, and estimated the number of burn beds theoretically available if the "50 [burn injury] cases per million people" directive were to be applied to metropolitan areas outside the United States. Seven hundred fifty-two burn disaster incidents met our inclusion criteria. The majority of burn disasters occurred in Asia/Middle East. The incidence of major burn disasters from structural fires and industrial blasts remains constant in high-income and resource-restricted countries during this study period. The incidence of terrorist attacks increased 20-fold from 2001 to 2015 compared with 1990 to 2000. Recent incidents demonstrate that if current preparedness guidelines were to be adopted internationally, local resources including burn-bed availability would be insufficient to care for the total number of burn casualties. These findings underscore an urgent need to organize better regional, national, and international collaboration in burn disaster response. PMID- 27654866 TI - Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways. AB - BACKGROUND: Bicyclol, a novel synthetic antihepatitis drug, is widely known to protect against liver injury. However, few reports have focused on the possible effect of bicyclol on anti-proliferation and autophagy induction in cancer cells, particularly hepatocellular carcinoma cells. METHODS: In this study, we investigated the antitumor efficacy of Bicyclol in HepG2 cells and the mechanism of cell growth inhibition. Cell proliferation was analyzed by MTT assay, and the cell cycle and apoptosis were assessed by flow cytometry. And we transfected the cells with the GFP-RFP-LC3 vector to detect the autophagy flux in the cells. Mechanisms of bicyclol-induced cell growth inhibition were probed by western blot analysis. RESULTS: Bicyclol effectively inhibited HepG2 cell proliferation in a dose- and time-dependent manner. In addition, we found that bicyclol inhibited cell cycle progression at G1 phase and induced autophagy in HepG2 cells, which implied that the significant decrease in cell proliferation was mainly induced by autophagy and inhibition of cell proliferation. Furthermore, western blot showed that bicyclol inhibited phosphorylation of Akt and ERK, down-regulated the expressions of cyclin D1, cyclin E2, CDK2, CDK4, p-Rb and p-mTOR. Moreover, AKT or ERK knockdown by siRNA enhanced bicyclol-induced autophagy and inhibition of cell proliferation. CONCLUSION: These results suggest that bicyclol has potent anti-proliferative activity against malignant human hepatoma cells via modulation of the PI3K/AKT pathway and the Ras/Raf/MEK/ERK pathway, and indicate that bicyclol is a potential liver cancer drug worthy of further research and development. PMID- 27654869 TI - Visible and invisible stimulus parts integrate into global object representations as revealed by combining monocular and binocular rivalry. AB - Our visual system faces the challenging task to construct integrated visual representations from the visual input projected on our retinae. Previous research has provided mixed evidence as to whether visual awareness of the stimulus parts is required for such integration to occur. Here, we address this issue by taking a novel approach in which we combine a monocular rivalry stimulus (i.e., a bistable rotating cylinder) with binocular rivalry. The results of Experiment 1 show that in a rivalry condition, where one half of the cylinder is perceptually suppressed, significantly more perceptual switches occur that are consistent with visual integration of the whole cylinder than occur in a control condition, where only half of the cylinder is presented at a time and the presentation of the two images is physically alternated. In Experiment 2, stimulation in the observer's dominant eye was kept dominant by presenting the half cylinder in this eye at higher contrast and by surrounding it with a flickering context. Results show that the strong convexity bias that was found in a control condition, where no stimulus was presented in the suppressed eye, almost completely disappears when the unseen half is presented in the suppressed eye, indicating that both halves visually integrate and, subsequently, compete for convexity. These findings provide evidence that unseen visual information is biased towards a representation that is congruent with the current visible representation and, hence, that principles of perceptual organization also apply to parts of the visual input that remain unseen by the observer. PMID- 27654868 TI - Functional Exercise Capacity in Children With Electrical Burns. AB - Electrical burns are a severe form of thermal injury extending deep into tissue. Here, we investigated the effect of electrical burns on metabolic rate, body composition, and aerobic capacity. We prospectively studied a cohort of 24 severely burned children. Twelve patients had a combination of electrical and flame burns and 12 matched controls had only flame burns. Endpoints were cardiopulmonary fitness (maximal oxygen consumption [VO2]), muscle strength (peak torque per body weight), body mass index, lean body mass index, and days of myoglobinemia (>=500 mg/dl). Demographics of both the groups were comparable. The electrical burn group had more days of myoglobinemia during acute hospitalization than the flame burn group (3.6 +/- 1.8 days vs 0.3 +/- 0.5 days, P < .0001). Maximal VO2 was significantly lower in the electrical burn group than in the flame burn group at intensive care unit discharge (27 +/- 6 ml/kg/min vs 34 +/- 5 ml/kg/min, P < .0014). Electrical burns are associated with myoglobinemia and decreased cardiopulmonary fitness. PMID- 27654870 TI - Effect of overlaid luminance contrast on perceived color contrast: Shadows enhance, borders suppress. AB - Natural scenes contain both color and luminance variations at different sizes and orientations that are sometimes spatially overlaid and sometimes not. Here, we explore visual interactions between overlaid color and luminance contrast that are both suprathreshold and highly visible. We used a color-luminance plaid in which the perception of the color contrast and luminance contrast components were measured separately using a method of constant stimuli, to reveal how overlaid cross-oriented luminance contrast affects perceived color contrast, and how color contrast affects perceived luminance contrast. Binocular, monocular, and dichoptic viewing conditions were used for different spatial frequencies (0.375 1.5 cpd, 2 Hz) and base contrasts. We find that overlaid, cross-oriented luminance contrast enhances perceived color contrast by an average of 32% (monocularly and binocularly) across a wide range of luminance contrasts, but interocularly suppresses color contrast. For the reverse condition, we found no effect of color contrast on perceived luminance contrast. If, however, the cross oriented arrangement is changed to co-oriented, specifically with the color and luminance borders aligned and in-phase, the color enhancement disappears and becomes mild suppression. Likewise, if the phase of the co-aligned components is varied, color enhancement returns once the color and luminance borders are misaligned and out of phase. Thus the relative position of the color and luminance borders is a crucial factor in determining the type of interaction, with color suppression occurring when the luminance and color borders coincide, as when demarcating an object boundary, and color enhancement when they do not coincide, as occurs in shadows and shading. PMID- 27654871 TI - Representation and measurement of stereoscopic volumes. AB - Binocular disparity information provides the human visual system with a basis for the compelling perception of both three-dimensional (3-D) object shape, and of the 3-D space between objects. However, while an extensive body of research exists into the perception of disparity-defined surface shape, relatively little research has been conducted on the associated perception of disparity-defined volume. In this paper, we report three experiments that examine this aspect of binocular vision. Participants were asked to make judgments about the 3-D spread, location-in-depth, and 3-D shape of stereoscopic volumes. Volumes were comprised of random dots with disparities drawn from a uniform distribution, a Gaussian distribution, or a combination of both. These results were compared to two models: One of these made judgments about stereoscopic volumes using information about the distributions of disparities in each stimulus, while the other was limited to only maximum and minimum disparity information. Psychophysical results were best accounted for by the maximum-minimum decision rule model. This suggests that, although binocular vision affords a compelling phenomenal sense of 3-D volume, when required to make judgments about such volumes, the visual system's default strategies make only limited use of available binocular disparity signals. PMID- 27654873 TI - Timing of Initiation of Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury. PMID- 27654874 TI - Diagnosing Traumatic Encephalopathy Syndrome-Reply. PMID- 27654872 TI - PharmGKB summary: very important pharmacogene information for MT-RNR1. PMID- 27654878 TI - Sphingomonas piscinae sp. nov., isolated from a fish pond. AB - A bacterial strain designated LYH-20T was isolated from a fish pond in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain LYH-20T were aerobic, Gram-stain-negative, non-motile, poly-beta-hydroxybutyrate containing, showing straight and rod shaped that were covered by large capsules and formed yellow-coloured colonies. Growth occurred at 15-40 degrees C (optimum, 30 degrees C), with 0-1.0 % NaCl (optimum, 0-0.1 %) and at pH 5.0-9.0 (optimum, pH 8.0-9.0). According to a phylogenetic tree based on 16S rRNA gene sequence analysis, strain LYH-20T belonged to the genus Sphingomonas and clustered with Sphingomonas fonticola TNR-2T, with which it shared the highest 16S rRNA gene sequence similarity (97.5 %). The major fatty acids (>10 %) of strain LYH-20T were C18 : 1omega7c and C16 : 0. The DNA G+C content was 67.5 mol%. The sole isoprenoid quinone was Q-10. The polyamines detected were spermidine, putrescine and homospermidine. The polar lipid profile consisted of a mixture of sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol and three uncharacterized phospholipids. The DNA-DNA hybridization value for strain LYH-20T with Sphingomonas fonticola TNR-2T was less than 35 %. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Sphingomonas. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain LYH-20T represents a novel species in the genus Sphingomonas, for which the name Sphingomonas piscinae sp. nov. is proposed. The type strain is LYH 20T (=BCRC 80911T=LMG 29002T=KCTC 42741T). PMID- 27654876 TI - Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons. AB - The Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be cleaved revealed that midline repulsion is still present but longitudinal axon guidance is disrupted, particularly across segment boundaries. Double mutants for the Slit receptors Dscam1 and robo1 strongly resemble the slit-UC phenotype, suggesting they cooperate in longitudinal axon guidance, and through biochemical approaches, we found that Dscam1 and Robo1 form a complex dependent on Slit-N. In contrast, Robo1 binding alone shows a preference for full-length Slit, whereas Dscam1 only binds Slit-N. Using a variety of transgenes, we demonstrated that Dscam1 appears to modify the output of Robo/Slit complexes so that signaling is no longer repulsive. Our data suggest that the complex is promoting longitudinal axon growth across the segment boundary. The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins. PMID- 27654877 TI - Duration of fascicle shortening is affected by muscle architecture and sex. AB - PURPOSE: The purpose of this study was to examine muscle fascicle properties of the gastrocnemius medialis (GM) during contraction and stretch between males and females. During contraction muscle fascicles shorten and pennation angles increase to generate force. Due to the elastic nature of the attached tendon, the fascicles continue to shorten when maximal force is achieved in order to sustain isometric force and this duration of fascicle shortening (DFS) can be observed with ultrasonography. Linear and curved muscle fascicles both display these kinetics; however, it is currently unknown if static stretch prior to a maximal voluntary contraction (MVC) alters the DFS and whether the effect differs between males and females. METHODS: Subjects performed an isometric MVC of the plantar flexors before and after a 2-min maximal dorsi-flexion stretch. Plantar flexor force was measured and ultrasound videography used to record GM and Achilles tendon architecture. RESULTS: Males were stronger than females (p = 0.004). The DFS was longer for females compared to males (p = 0.001) and the addition of a static stretch increased the DFS for curved (p = 0.002), but not linear, fascicles. Curved fascicles were longer (p = 0.05) with larger pennation angles (p = 0.04) for both males and females when compared to linear fascicles. Tendon excursion was greater (p = 0.05) post-stretch during contraction when compared to pre-stretch. CONCLUSIONS: This study provides evidence that regardless of sex, curved muscle fascicles behave differently than linear fascicles and should be considered separately when muscle architecture is examined. PMID- 27654879 TI - Brainstem sources of cardiac vagal tone and respiratory sinus arrhythmia. AB - KEY POINTS: Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. Respiratory-linked fluctuations in cardiac vagal tone give rise to respiratory sinus arryhthmia (RSA), with maximum tone in the post-inspiratory phase of respiration. In the present study, we investigated whether respiratory modulation of cardiac vagal tone is intrinsically linked to post-inspiratory respiratory control using the unanaesthetized working heart brainstem preparation of the rat. Abolition of post-inspiration, achieved by inhibition of the pontine Kolliker-Fuse nucleus, removed post-inspiratory peaks in efferent cardiac vagal activity and suppressed RSA, whereas substantial cardiac vagal tone persisted. After transection of the caudal pons, part of the remaining tone was removed by inhibition of nucleus of the solitary tract. We conclude that cardiac vagal tone depends upon at least 3 sites of the pontomedullary brainstem and that a significant proportion arises independently of RSA. ABSTRACT: Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. The rat working heart-brainstem preparation shows strong cardiac vagal tone and pronounced respiratory sinus arrhythmia. In this preparation, recordings from the cut left cardiac vagal branch showed efferent activity that peaked in post-inspiration, ~0.5 s before the cyclic minimum in heart rate (HR). We hypothesized that respiratory modulation of cardiac vagal tone and HR is intrinsically linked to the generation of post inspiration. Neurons in the pontine Kolliker-Fuse nucleus (KF) were inhibited with bilateral microinjections of isoguvacine (50-70 nl, 10 mm) to remove the post-inspiratory phase of respiration. This also abolished the post-inspiratory peak of cardiac vagal discharge (and cyclical HR modulation), although a substantial level of activity remained. In separate preparations with intact cardiac vagal branches but sympathetically denervated by thoracic spinal pithing, cardiac chronotropic vagal tone was quantified by HR compared to its final level after systemic atropine (0.5 MUm). Bilateral KF inhibition removed 88% of the cyclical fluctuation in HR but, on average, only 52% of the chronotropic vagal tone. Substantial chronotropic vagal tone also remained after transection of the brainstem through the caudal pons. Subsequent bilateral isoguvacine injections into the nucleus of the solitary tract further reduced vagal tone: remaining sources were untraced. We conclude that cardiac vagal tone depends on neurons in at least three sites of the pontomedullary brainstem, and much of it arises independently of respiratory sinus arrhythmia. PMID- 27654881 TI - Stiffened Extracellular Matrix and Signaling from Stromal Fibroblasts via Osteoprotegerin Regulate Tumor Cell Invasion in a 3-D Tumor in Situ Model. AB - Several changes have been described in the stroma surrounding a tumor, including changes in cellular composition, altered extracellular matrix composition and organization, and increases in stiffness. Tumor cells are influenced by the composition, organization, and mechanical properties of the microenvironment, and by signals from stromal cells. Here we sought to test whether signaling from stromal fibroblasts and/or the small change in stiffness observed in vivo surrounding epithelial tumors regulates tumor cell invasion from a model of a tumor in situ. We generated a novel tumor in situ model system in which a tumor spheroid is encased within a collagen-IV containing membrane and further encased within a collagen-I matrix of in vivo stiffness with or without fibroblasts. Effects of the matrix, fibroblasts or fibroblast signals were determined by observing the invasion of tumor cells into the matrix. Effects of reciprocal tumor cell signaling upon fibroblasts were determined by observing markers of fibroblast activation. We found that a stiffened matrix led to increased dissemination of MDA-MB-231 cells from tumor spheroids when no fibroblasts were present and that MCF10A cells maintained a more normal organization with a stiffened matrix. The presence of fibroblasts, or fibroblast conditioned media, attenuated the effect upon MDA-MB-231 cells. We also observed an attenuation of fibroblast activation associated gene expression in the presence of MDA-MB-231 cells, with a paradoxical increase in activation associated contractile activity. Furthermore, we identified osteoprotegerin as a soluble factor released by fibroblasts in the stiffened environment that is key to the inhibition of cell invasion. PMID- 27654880 TI - Relationship between structural and functional connectivity change across the adult lifespan: A longitudinal investigation. AB - Extensive efforts are devoted to understand the functional (FC) and structural connections (SC) of the brain. FC is usually measured by functional magnetic resonance imaging (fMRI), and conceptualized as degree of synchronicity in brain activity between different regions. SC is typically indexed by measures of white matter (WM) properties, for example, by diffusion weighted imaging (DWI). FC and SC are intrinsically related, in that coordination of activity across regions ultimately depends on fast and efficient transfer of information made possible by structural connections. Convergence between FC and SC has been shown for specific networks, especially the default mode network (DMN). However, it is not known to what degree FC is constrained by major WM tracts and whether FC and SC change together over time. Here, 120 participants (20-85 years) were tested at two time points, separated by 3.3 years. Resting-state fMRI was used to measure FC, and DWI to measure WM microstructure as an index of SC. TRACULA, part of FreeSurfer, was used for automated tractography of 18 major WM tracts. Cortical regions with tight structural couplings defined by tractography were only weakly related at the functional level. Certain regions of the DMN showed a modest relationship between change in FC and SC, but for the most part, the two measures changed independently. The main conclusions are that anatomical alignment of SC and FC seems restricted to specific networks and tracts, and that changes in SC and FC are not necessarily strongly correlated. Hum Brain Mapp 38:561-573, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27654883 TI - Comprehensive Reactive Receiver Modeling for Diffusive Molecular Communication Systems: Reversible Binding, Molecule Degradation, and Finite Number of Receptors. AB - This paper studies the problem of receiver modeling in molecular communication systems. We consider the diffusive molecular communication channel between a transmitter nano-machine and a receiver nano-machine in a fluid environment. The information molecules released by the transmitter nano-machine into the environment can degrade in the channel via a first-order degradation reaction and those that reach the receiver nano-machine can participate in a reversible bimolecular reaction with receiver receptor proteins. Thereby, we distinguish between two scenarios. In the first scenario, we assume that the entire surface of the receiver is covered by receptor molecules. We derive a closed-form analytical expression for the expected received signal at the receiver, i.e., the expected number of activated receptors on the surface of the receiver. Then, in the second scenario, we consider the case where the number of receptor molecules is finite and the uniformly distributed receptor molecules cover the receiver surface only partially. We show that the expected received signal for this scenario can be accurately approximated by the expected received signal for the first scenario after appropriately modifying the forward reaction rate constant. The accuracy of the derived analytical results is verified by Brownian motion particle-based simulations of the considered environment, where we also show the impact of the effect of receptor occupancy on the derived analytical results. PMID- 27654882 TI - A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity. AB - CONTEXT: Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity. OBJECTIVE: The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obesity. DESIGN: Dose-finding study of nondiabetic children ages 6 12 years with body mass index (BMI) >= 95th percentile given niacin 250 mg q2h * 3 doses (n = 2), 500 mg q2h * 3 doses (n = 5) or 500 mg q1h * 4 doses (n = 5). PARTICIPANTS: Eight boys and four girls (age 9.7 +/- 1.8 years; BMI 26.4 +/- 3.1 kg m-2 ; BMIz 2.2 +/- .25) were studied. MAIN OUTCOME: Percentage of serum FFA values that were below 0.2 mEq L-1 . GH, insulin and glucose were also measured serially. RESULTS: FFA decreased as the dose and frequency of niacin increased (p = .01). Niacin 500 mg q1h 4 doses suppressed FFA < 0.2 mEq L-1 and significantly increased GH (p = .04). Adverse effects were flushing/warmth (100%), tingling (60%) and GI complaints (20-40%). CONCLUSIONS: Niacin 500 mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity. PMID- 27654884 TI - Literature Review: Double-Barrelled Wet Colostomy (One Stoma) versus Ileal Conduit with Colostomy (Two Stomas). AB - INTRODUCTION: The aim of this literature review was to analyse the advantages and disadvantages of a traditional ileal conduit (IC) with separate colostomy technique compared to the outcomes of a double-barrelled wet colostomy (DBWC) technique. The former technique results in the formation of two stomas, and the latter results in the formation of one stoma. METHODS: PubMed was searched electronically for articles on DBWC. Fifteen articles were retrieved and of them 13 were included in the literature review (350 patients). Of the articles, 3 directly compared DBWC to IC with colostomy. RESULTS: Review of 13 DBWC articles demonstrated perioperative mortality ranging between 0 and 11.1% and postoperative complications ranging from 0 to 100%. Three of the studies directly compared DBWC to IC with colostomy; median operating times and length of stay were shorter in DBWC patients (p < 0.001); 30-day morbidity was reported to either be lower in the DBWC group (p < 0.043) or to have no statistically significant difference. Rates of mortality, pyelonephritis, electrolyte disturbances and urinary anastomotic problems did not differ between the 2 groups. CONCLUSION: The DBWC technique inherently has a benefit over the IC with colostomy technique, as it requires only one stoma. This literature review supports the use of the technically less challenging DBWC technique as a viable alternative to the traditional IC with colostomy technique. PMID- 27654885 TI - Postpolymerization Modifications of Alkene-Functional Polycarbonates for the Development of Advanced Materials Biomaterials. AB - Functional aliphatic polycarbonates have attracted significant attention as materials for use as biomedical polymers in recent years. The incorporation of pendent functionality offers a facile method of modifying materials postpolymerization, thus enabling functionalities not compatible with ring opening polymerization (ROP) to be introduced into the polymer. In particular, polycarbonates bearing alkene-terminated functional groups have generated considerable interest as a result of their ease of synthesis, and the wide range of materials that can be obtained by performing simple postpolymerization modifications on this functionality, for example, through radical thiol-ene addition, Michael addition, and epoxidation reactions. This review presents an in depth appraisal of the methods used to modify alkene-functional polycarbonates postpolymerization, and the diversity of practical applications for which these materials and their derivatives have been used. PMID- 27654886 TI - Outcome and Efficacy of Interventions by a Public Figure Threat Assessment and Management Unit: A Mirrored Study of Concerning Behaviors and Police Contacts Before and After Intervention. AB - Specialized units for the assessment and management of concerning behaviors towards public figures have been set up in various jurisdictions. Their efficacy has been demonstrated descriptively and in terms of reduction in concern rates. This study of 100 consecutive cases from the Fixated Threat Assessment Centre (FTAC) in the UK uses a novel measure of outcome in the form of reduction in behaviors of concern and in police call-outs/stops, using data culled from police and health service records. It adopts a mirrored design, comparing individuals over 12-month and 2-year periods before and after FTAC intervention. It demonstrates significant reductions in both numbers of individuals involved in, and number of actual incidents of, concerning communication and problematic approach, as well as police call-outs/stops. Most results are consistent across subgroups with regard to gender, previous convictions, concern level, compulsory hospitalization and grievance-driven behavior. Such threat assessment units reduce risky behavior and save police time and, possibly, costs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27654887 TI - THC (Delta9-Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti-apoptosis Involving CB1 Receptor-dependent Mechanism. AB - Aging-related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. Delta9-Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48 h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase-3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate-induced neurotoxicity. Moreover, THC significantly counteracted the glutamate-induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB1 receptor antagonist, concentration dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti-apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB1 receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27654888 TI - Aflibercept improves outcome in eyes with poor vision from neovascular age related macular degeneration. PMID- 27654889 TI - Characterization of a Zika Virus Isolate from Colombia. AB - BACKGROUND: Zika virus (Flavivirus genus) is the first mosquito-borne virus known to cause high rates of microcephaly and abortion in humans. Typically, Zika virus causes a self-limiting, systemic illness; however, the current outbreak of Zika virus in the Americas has been associated with increased rates of fetal malformations and Guillain-Barre syndrome. Very few Zika virus isolates have been described in the literature, and live viruses are needed to perform studies of pathogenesis and to develop vaccines and treatments. METHODOLOGY/CLINICAL FINDINGS: We isolated Zika virus, strain FLR, directly from the serum of an individual infected in Barranquilla, Colombia (December, 2015). Here, we describe the patient's clinical course and characterize strain FLR by its growth characteristics in mosquito and mammalian cells and its partial resistance to UV inactivation. The full genome sequence of FLR was also analyzed (including the 3' un-translated region), to determine its probable geographic origin, and to pinpoint structural differences from other Zika virus strains. CONCLUSIONS/SIGNIFICANCE: We anticipate that the study of this low passage, clinical isolate of Zika virus, which is available for worldwide distribution, will help uncover the mechanisms of viral replication and host immune responses contributing to the varied and sometimes severe clinical presentations seen during the current epidemic in the Americas. PMID- 27654890 TI - Use of ade1 and ade2 mutations for development of a versatile red/white colour assay of amyloid-induced oxidative stress in saccharomyces cerevisiae. AB - Mutations in adenine biosynthesis pathway genes ADE1 and ADE2 have been conventionally used to score for prion [PSI+ ] in yeast. If ade1-14 mutant allele is present, which contains a premature stop codon, [psi- ] yeast appear red on YPD medium owing to accumulation of a red intermediate compound in vacuoles. In [PSI+ ] yeast, partial inactivation of the translation termination factor, Sup35 protein, owing to its amyloid aggregation allows for read-through of the ade1-14 stop codon and the yeast appears white as the red intermediate pigment is not accumulated. The red colour development in ade1 and ade2 mutant yeast requires reduced-glutathione, which helps in transport of the intermediate metabolite P ribosylaminoimidazole carboxylate into vacuoles, which develops the red colour. Here, we hypothesize that amyloid-induced oxidative stress would deplete reduced glutathione levels and thus thwart the development of red colour in ade1 or ade2 yeast. Indeed, when we overexpressed amyloid-forming human proteins TDP-43, Abeta 42 and Poly-Gln-103 and the yeast prion protein Rnq1, the otherwise red ade1 yeast yielded some white colonies. Further, the white colour eventually reverted back to red upon turning off the amyloid protein's expression. Also, the aggregate-bearing yeast have increased oxidative stress and white phenotype yeast revert to red when grown on media with reducing agent. Furthermore, the red/white assay could also be emulated in ade2-1, ade2Delta, and ade1Delta mutant yeast and also in an ade1-14 mutant with erg6 gene deletion that increases cell-wall permeability. This model would be useful tool for drug-screening against general amyloid-induced oxidative stress and toxicity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27654893 TI - Lengths of nephron tubule segments and collecting ducts in the CD-1 mouse kidney: an ontogeny study. AB - The kidney continues to mature postnatally, with significant elongation of nephron tubules and collecting ducts to maintain fluid/electrolyte homeostasis. The aim of this project was to develop methodology to estimate lengths of specific segments of nephron tubules and collecting ducts in the CD-1 mouse kidney using a combination of immunohistochemistry and design-based stereology (vertical uniform random sections with cycloid arc test system). Lengths of tubules were determined at postnatal day 21 (P21) and 2 and 12 mo of age and also in mice fed a high-salt diet throughout adulthood. Immunohistochemistry was performed to identify individual tubule segments [aquaporin-1, proximal tubules (PT) and thin descending limbs of Henle (TDLH); uromodulin, distal tubules (DT); aquaporin-2, collecting ducts (CD)]. All tubular segments increased significantly in length between P21 and 2 mo of age (PT, 602% increase; DT, 200% increase; TDLH, 35% increase; CD, 53% increase). However, between 2 and 12 mo, a significant increase in length was only observed for PT (76% increase in length). At 12 mo of age, kidneys of mice on a high-salt diet demonstrated a 27% greater length of the TDLH, but no significant change in length was detected for PT, DT, and CD compared with the normal-salt group. Our study demonstrates an efficient method of estimating lengths of specific segments of the renal tubular system. This technique can be applied to examine structure of the renal tubules in combination with the number of glomeruli in the kidney in models of altered renal phenotype. PMID- 27654894 TI - An experimentum crucis in salt sensitivity. PMID- 27654891 TI - Sex-dependent expression of TRPV1 in bladder arterioles. AB - Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1PLAP nlacZ) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15-40 MUm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca2+ in ~15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions. PMID- 27654895 TI - In situ lactate dehydrogenase activity: a novel renal cortical imaging biomarker of tubular injury? AB - Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized 13C-pyruvate MRI enables noninvasive accurate quantification of the in vivo conversion of pyruvate to lactate, alanine, and bicarbonate. In the present study, we investigated the in situ alterations of metabolic conversion of pyruvate to lactate, alanine, and bicarbonate in a unilateral I/R-I rat model with 30 min and 60 min of ischemia followed by 24 h of reperfusion. The pyruvate conversion was unaltered compared with sham in the 30 min I/R-I group, while a significant reduced metabolic conversion was found in the postischemic kidney after 60 min of ischemia. This indicates that after 30 min of ischemia, the kidney maintains normal metabolic function in spite of decreased kidney function, whereas the postischemic kidney after 60 min of ischemia show a generally reduced metabolic enzyme activity concomitant with a reduced kidney function. We have confidence that these findings can have a high prognostic value in prediction of kidney injury and the outcome of renal injury. PMID- 27654892 TI - Functional and therapeutic importance of purinergic signaling in polycystic kidney disease. AB - Polycystic kidney diseases (PKD) are a group of inherited nephropathies marked with the formation of fluid-filled cysts along the nephron. This renal disorder affects millions of people worldwide, but current treatment strategies are unfortunately limited to supportive therapy, dietary restrictions, and, eventually, renal transplantation. Recent advances in PKD management are aimed at targeting exaggerated cell proliferation and dedifferentiation to interfere with cyst growth. However, not nearly enough is known about the ion transport properties of the cystic cells, or specific signaling pathways modulating channels and transporters in this condition. There is growing evidence that abnormally elevated concentrations of adenosine triphosphate (ATP) in PKD may contribute to cyst enlargement; change in the profile of purinergic receptors may also result in promotion of cystogenesis. The current mini-review is focused on the role of ATP and associated signaling affecting ion transport properties of the renal cystic epithelia. PMID- 27654897 TI - Simulation modelling as a tool for knowledge mobilisation in health policy settings: a case study protocol. AB - BACKGROUND: Evidence-informed decision-making is essential to ensure that health programs and services are effective and offer value for money; however, barriers to the use of evidence persist. Emerging systems science approaches and advances in technology are providing new methods and tools to facilitate evidence-based decision-making. Simulation modelling offers a unique tool for synthesising and leveraging existing evidence, data and expert local knowledge to examine, in a robust, low risk and low cost way, the likely impact of alternative policy and service provision scenarios. This case study will evaluate participatory simulation modelling to inform the prevention and management of gestational diabetes mellitus (GDM). The risks associated with GDM are well recognised; however, debate remains regarding diagnostic thresholds and whether screening and treatment to reduce maternal glucose levels reduce the associated risks. A diagnosis of GDM may provide a leverage point for multidisciplinary lifestyle modification interventions. This research will apply and evaluate a simulation modelling approach to understand the complex interrelation of factors that drive GDM rates, test options for screening and interventions, and optimise the use of evidence to inform policy and program decision-making. METHODS/DESIGN: The study design will use mixed methods to achieve the objectives. Policy, clinical practice and research experts will work collaboratively to develop, test and validate a simulation model of GDM in the Australian Capital Territory (ACT). The model will be applied to support evidence-informed policy dialogues with diverse stakeholders for the management of GDM in the ACT. Qualitative methods will be used to evaluate simulation modelling as an evidence synthesis tool to support evidence-based decision-making. Interviews and analysis of workshop recordings will focus on the participants' engagement in the modelling process; perceived value of the participatory process, perceived commitment, influence and confidence of stakeholders in implementing policy and program decisions identified in the modelling process; and the impact of the process in terms of policy and program change. DISCUSSION: The study will generate empirical evidence on the feasibility and potential value of simulation modelling to support knowledge mobilisation and consensus building in health settings. PMID- 27654898 TI - Recent Advances in Drug Delivery of Polymeric Nano-Micelles. AB - In clinical studies, drugs with hydrophobic characteristic usually reflect low bioavailability, poor drug absorption, and inability to achieve the therapeutic concentration in blood. The production of poor solubility drugs, in abundance, by pharmaceutical industries calls for an urgent need to find the alternatives for resolving the above mentioned shortcomings. Poor water solubility drugs loaded with polymeric micelle seem to be the best alternative to enhance drugs solubility and bioavailability. Polymeric micelle, formed by self-assembled of amphiphilic block copolymers in aqueous environment, functioned as solubilizing agent for hydrophobic drug. This review discusses the fundamentals of polymeric micelle as drug carrier through representative literature, and demonstrates some applications in various clinical trials. The structure, characteristic, and formation of polymeric micelle have been discussed firstly. Next, this manuscript focuses on the potential of polymeric micelles as drug vehicle in oral, transdermal routes, and anti-cancer agent. Several results from previous studies have been reproduced in this review in order to prove the efficacy of the micelles in delivering hydrophobic drugs. Lastly, future strategies to broaden the application of polymeric micelles in pharmaceutical industries have been highlighted. PMID- 27654896 TI - Blocking peptides and molecular mimicry as treatment for kidney disease. AB - Protein mimotopes, or blocking peptides, are small therapeutic peptides that prevent protein-protein interactions by selectively mimicking a native binding domain. Inexpensive technology facilitates straightforward design and production of blocking peptides in sufficient quantities to allow preventive and therapeutic trials in both in vitro and in vivo experimental disease models. The kidney is an ideal peptide target, since small molecules undergo rapid filtration and efficient bulk absorption by tubular epithelial cells. Because the half-life of peptides is markedly prolonged in the kidneys compared with the bloodstream, blocking peptides are an attractive tool for treating diverse renal diseases, including ischemia, proteinuric states, such as membranous nephropathy and focal and segmental glomerulosclerosis, and renal cell carcinoma. Therapeutic peptides represent one of the fastest-growing reagent classes for novel drug development in human disease, partly because of their ease of administration, high binding affinity, and minimal off-target effects. This review introduces the concepts of blocking peptide design, production, and administration and highlights the potential use of therapeutic peptides to prevent or treat specific renal diseases. PMID- 27654899 TI - Genetic and Non-Genetic Determinants of the Pharmacological Activity of Statins. AB - Statins are cholesterol-lowering agents which belong to the group of the most commonly prescribed drugs. The use of statins has become the standard treatment in patients with an increased risk of cardiovascular and coronary heart diseases. However, many clinical studies have shown that 13 - 75% of patients fail to achieve LDL-cholesterol and total cholesterol target levels. The clinical implications of insufficient response include cardiovascular complications caused by atherosclerosis leading to acute myocardial infarction, stroke and death. The mechanism underlying statin resistance has been associated with genetic polymorphisms and nongenetic factors (e.g. concomitant diseases, drug-drug interactions, interactions with food and dietary supplements). The article provides a comprehensive update of the current knowledge regarding the role of genetic polymorphism and non-genetic determinants of cholesterol-lowering effect of statins. Dietary aspects of statin efficacy were also presented. The Pubmed search was performed to identify relevant papers from the last ten years which were included in the review. Consideration of the genetic and non-genetic determinants of pharmacological action of statins as well as mechanisms of drug drug interactions may be useful in clinical practice for improving safety and efficacy of statin treatment. PMID- 27654900 TI - Inhalation anesthesia induced by isoflurane alters penicillin disposition in swine tissues. AB - Twelve healthy swine were dosed with penicillin G intramuscularly. Fluids and tissues samples were collected at the end of two periods of general anesthesia, performed 24 h apart. Tissue samples were collected by minimally invasive laparoscopy under general anesthesia at 8 and 28 h postdose. Four nonanesthetized, penicillin-treated pigs were euthanized at 8 h postdose, and a second set of four similarly treated control pigs were sacrificed 28 h postdose. Liver penicillin tissue concentrations from animals that underwent anesthesia and laparoscopic tissue collection had tissue concentrations that were higher than nonanesthetized pigs at both time points. Urine, plasma, kidney, skeletal, and cardiac muscle showed no differences between the two groups. Laparoscopic tissue collection under general anesthesia in swine induces physiological changes that cause alterations in tissue pharmacokinetics not seen in conscious animals. PMID- 27654901 TI - HF-Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization. AB - We have developed a convenient method for the direct synthesis of peptide thioesters, versatile intermediates for peptide ligation and cyclic peptide synthesis. The technology uses a modified Boc SPPS strategy that avoids the use of anhydrous HF. Boc in situ neutralization protocols are used in combination with Merrifield hydroxymethyl resin and TFA/TMSBr cleavage. Avoiding HF extends the scope of Boc SPPS to post-translational modifications that are compatible with the milder cleavage conditions, demonstrated here with the synthesis of the phosphorylated protein CHK2. Peptide thioesters give easy, direct, access to cyclic peptides, illustrated by the synthesis of cyclorasin, a KRAS inhibitor. PMID- 27654902 TI - Cost-effectiveness of cognitive remediation and supported employment for people with mental illness: a randomized controlled trial. AB - BACKGROUND: Little is known about the economic benefits of cognitive remediation and supported employment (CR + SE). The present study aimed to investigate the cost-effectiveness of CR + SE compared with traditional vocational services (TVS). METHOD: Individuals with mental illness and low cognitive function were recruited at six sites in Japan. A total of 111 participants were randomly allocated to the CR + SE group or the TVS group. Clinical and vocational outcomes were assessed at baseline and 12-month follow-up. Service utilization data were collected monthly. The data on outcomes and costs were combined to examine cost effectiveness. RESULTS: The data were obtained from a total of 92 participants. The CR + SE group resulted in better vocational and clinical outcomes (employment rate, 62.2%; work tenures, 78.6 days; cognitive improvement, 0.5) than the TVS group (19.1%, 24.9 days and 0.2). There was no significant difference in mean total costs between the groups (CR + SE group: $9823, s.d. = $6372, TVS group: $11 063, s.d. = $11 263) with and without adjustment for covariates. However, mean cost for medical services in the CR + SE group was significantly lower than that in the TVS group after adjusting covariates (Beta = -$3979, 95% confidence interval -$7816 to -$143, p = 0.042). Cost-effectiveness acceptability curves for vocational outcomes illustrated the high probabilities (approximately 70%) of the CR + SE group being more cost-effective than TVS when society is not willing to pay additional costs. CONCLUSIONS: CR + SE appears to be a cost-effective option for people with mental illness who have low cognitive functioning when compared with TVS. PMID- 27654904 TI - Response to Letter Regarding 'Pregnancy Following Bariatric Surgery-Medical Complications and Management'. PMID- 27654905 TI - The evolving local social contract for managing climate and disaster risk in Vietnam. AB - How do disasters shape local government legitimacy in relation to managing climate- and disaster-related risks? This paper looks at how local authorities in Central Vietnam perceive their social contract for risk reduction, including the partial merging of responsibilities for disaster risk management with new plans for and investments in climate change adaptation and broader socioeconomic development. The findings indicate that extreme floods and storms constitute critical junctures that stimulate genuine institutional change. Local officials are proud of their strengthened role in disaster response and they are eager to boost investment in infrastructure. They have struggled to reinforce their legitimacy among their constituents, but given the shifting roles of the state, private sector, and civil society, and the undiminished emphasis on high-risk development models, their responsibilities for responding to emerging climate change scenarios are increasingly nebulous. The past basis for legitimacy is no longer valid, but tomorrow's social contract is not yet defined. PMID- 27654903 TI - Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Pancreatic Islets from Zucker Diabetic Fatty Rats. AB - PURPOSE: Diabetes and obesity are associated with inflammasome-mediated low grade, chronic inflammation that may induce pancreatic beta-cell dysfunction and apoptosis. We examined the effects of Roux-en-Y gastric bypass (RYGB) surgery on NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome-related genes from pancreatic islets of Zucker diabetic fatty rats. MATERIALS AND METHODS: Islets were collected from Zucker diabetic fatty sham control and RYGB, 30 days after surgery. We assessed expression of genes that regulate glucose metabolism and the NLRP3 inflammasome (NLRP3, caspase-1, IL-1beta, IL-18, apoptosis-associated speck-like protein), IL-6, and monocyte chemoattractant protein-1. RESULTS: Gene expression for NLRP3 (p < 0.02), IL-1beta (p < 0.04), and IL-6 (p < 0.01) was reduced by RYGB and positively correlated with change in body weight. IL-1beta positively correlated with glucose AUC response. CONCLUSION: Suppression of the NLRP3 inflammasome in pancreatic islets may contribute to improved glycemic control after RYGB. PMID- 27654906 TI - Breast cancer screening-opportunistic use of registry and linked screening data for local evaluation. AB - RATIONALE: Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more common prognostic and treatment measures and survivals to gain evidence of screening effects among patients attending 4 local hospitals for treatment. AIMS AND OBJECTIVES: To compare prognostic, treatment, and survival measures by screening history to determine whether expected screening effects are occurring. METHODS: Employing routine clinical registry and linked screening data to investigate associations of screening history with these measures, using unadjusted and adjusted analyses. RESULTS: Screened women had a 10-year survival from breast cancer of 92%, compared with 78% for unscreened women; and 79% of screened surgical cases had breast conserving surgery compared with 64% in unscreened women. Unadjusted analyses indicated that recently screened cases had earlier tumor node metastasis stages, smaller diameters, less nodal involvement, better tumor differentiation, more oestrogen and progesterone receptor positive lesions, more hormone therapy, and less chemotherapy. Radiotherapy tended to be more common in screening participants. More frequent use of adjunctive radiotherapy applied when breast conserving surgery was used. CONCLUSIONS: Results confirm the screening effects expected from the scientific literature and demonstrate the value of opportunistic use of available registry and linked screening data for indicating to local health administrations, practitioners, and consumers whether local screening services are having the effects expected. PMID- 27654907 TI - Effect of Female Body Mass Index on Oocyte Quantity in Fertility Treatments (IVF): Treatment Cycle Number Is a Possible Effect Modifier. A Register-Based Cohort Study. AB - INTRODUCTION: Overweight and obese women may require higher doses of gonadotrophin when undergoing In Vitro Fertilization Treatment (IVF). Consequently, one may expect a sub-optimal oocyte retrieval in the first treatment cycle and thus a larger compensation in gonadotrophin-dose in the following treatment-cycles and a more favorable outcome. The main objective was to explore if treatment cycle number modifies the outcome when investigating the effect of female Body Mass Index (BMI) on oocyte quantity in IVF. MATERIAL AND METHODS: A historical cohort study was conducted on 5,342 treatment-cycles during the period 1999-2009. Exclusion criteria were missing information on BMI or treatment type. Further, women were excluded if they had ovulated before oocyte retrieval. According to baseline BMI, women were divided into four categories following the World Health Organization standards. Multiple linear regressions analyses were performed accounting for the non-independence of >=2 cycles in a woman. RESULTS: Stratification according to cycle number revealed a more suboptimal outcome in the first treatment- cycles than in the following cycles, suggesting a possible interaction or effect modification from cycle number or a factor related to cycle number. The median dose of total follicular stimulating hormone given to the four BMI groups could not straight forwardly explain the less optimal oocyte outcome observed in first treatment cycles. No statistically significant differences were observed in oocyte yield for underweight, overweight and obesity compared to normal weight women when analyzing all treatment-cycles. Overweight women had significantly fewer mature (MII) oocytes (p = 0.009) than normal weight women, whereas no differences was observed for underweight and obese women. CONCLUSION: Our study suggests a possible interaction or effect modification related to treatment cycle number. Investigating the effects of BMI on IVF-results in first treatment-cycles alone should be carried out cautiously. PMID- 27654908 TI - Acute encephalopathy: When febrile status more than 'fits'. PMID- 27654909 TI - [Acute kidney injury : A clinical syndrome]. AB - Acute kidney injury (AKI) is a clinical syndrome occurring in the context of multiple and diverse disease entities. Although the term AKI implies renal damage as well as functional impairment or a combination of both, diagnosis is solely based on the functional parameters serum creatinine and urine output. Independent of the underlying disease and even assuming full recovery of renal function, AKI is associated with increased morbidity and mortality not only during the acute situation, but also long term. Awareness of the individual risk profile of each patient and the variety of causes and clinical manifestations of AKI is pivotal for prophylaxis, diagnosis, and therapy. The complexity of the clinical syndrome in the context of sepsis, solid organ transplantation, malignancy, and autoimmune diseases requires differentiated diagnostic and therapeutic approaches and interdisciplinary care. PMID- 27654911 TI - Particle physics: Search for neutrinoless double-beta decay. PMID- 27654910 TI - Genomic analyses inform on migration events during the peopling of Eurasia. AB - High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago. PMID- 27654912 TI - The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. AB - Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans. PMID- 27654915 TI - Human migration: Climate and the peopling of the world. PMID- 27654913 TI - The architecture of respiratory supercomplexes. AB - Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo electron microscopy. We identify two distinct arrangements of supercomplex CICIII2CIV (the respirasome)-a major 'tight' form and a minor 'loose' form (resolved at the resolution of 5.8 A and 6.7 A, respectively), which may represent different stages in supercomplex assembly or disassembly. We have also determined an architecture of supercomplex CICIII2 at 7.8 A resolution. All observed density can be attributed to the known 80 subunits of the individual complexes, including 132 transmembrane helices. The individual complexes form tight interactions that vary between the architectures, with complex IV subunit COX7a switching contact from complex III to complex I. The arrangement of active sites within the supercomplex may help control reactive oxygen species production. To our knowledge, these are the first complete architectures of the dominant, physiologically relevant state of the electron transport chain. PMID- 27654916 TI - Population genetics: A map of human wanderlust. PMID- 27654914 TI - A genomic history of Aboriginal Australia. AB - The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert. PMID- 27654917 TI - The architecture of the mammalian respirasome. AB - The respiratory chain complexes I, III and IV (CI, CIII and CIV) are present in the bacterial membrane or the inner mitochondrial membrane and have a role of transferring electrons and establishing the proton gradient for ATP synthesis by complex V. The respiratory chain complexes can assemble into supercomplexes (SCs), but their precise arrangement is unknown. Here we report a 5.4 A cryo electron microscopy structure of the major 1.7 megadalton SCI1III2IV1 respirasome purified from porcine heart. The CIII dimer and CIV bind at the same side of the L-shaped CI, with their transmembrane domains essentially aligned to form a transmembrane disk. Compared to free CI, the CI in the respirasome is more compact because of interactions with CIII and CIV. The NDUFA11 and NDUFB9 supernumerary subunits of CI contribute to the oligomerization of CI and CIII. The structure of the respirasome provides information on the precise arrangements of the respiratory chain complexes in mitochondria. PMID- 27654918 TI - Rewriting yeast central carbon metabolism for industrial isoprenoid production. AB - A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as beta-farnesene (C15H24), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO2-emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained. Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches >15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost effective, large-scale production of acetyl-CoA-derived molecules. PMID- 27654919 TI - Structural insight into the role of the Ton complex in energy transduction. AB - In Gram-negative bacteria, outer membrane transporters import nutrients by coupling to an inner membrane protein complex called the Ton complex. The Ton complex consists of TonB, ExbB, and ExbD, and uses the proton motive force at the inner membrane to transduce energy to the outer membrane via TonB. Here, we structurally characterize the Ton complex from Escherichia coli using X-ray crystallography, electron microscopy, double electron-electron resonance (DEER) spectroscopy, and crosslinking. Our results reveal a stoichiometry consisting of a pentamer of ExbB, a dimer of ExbD, and at least one TonB. Electrophysiology studies show that the Ton subcomplex forms pH-sensitive cation-selective channels and provide insight into the mechanism by which it may harness the proton motive force to produce energy. PMID- 27654920 TI - Late Pleistocene climate drivers of early human migration. AB - On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50-120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106-94, 89-73, 59-47 and 45-29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial scale abrupt climate changes, associated with Dansgaard-Oeschger events, had a more limited regional effect. PMID- 27654922 TI - Expression of the zinc importer protein ZIP9/SLC39A9 in glioblastoma cells affects phosphorylation states of p53 and GSK-3beta and causes increased cell migration. AB - Zinc importer proteins (ZIPs) have been proven as important molecular regulators in different cancers. As a member of the solute carrier family, ZIP9/SLC39A9 is overexpressed in prostate and breast cancer and affects B-cell receptor signaling. Here, we present data indicating that changes in intracellular zinc levels in glioblastoma cells can cause enhanced cell survival and cell migration, both hallmarks of the disease process. In particular, treatment of human glioblastoma cells with sublethal doses of cell-permeable heavy metal (Zn2+ > Fe2+ > Mn2+) chelator (N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN)) induced ZIP9 expression. Either TPEN treatment or expression of ZIP9 cDNA causes enhanced migration behavior of glioblastoma cells. Compared to untreated glioblastoma cells TPEN treatment or expression of ZIP9 results in activation of the tumor suppressor p53 by phosphorylation at serine residue 46 (Ser46) and in inactivation of the migration relevant glycogen synthase kinase 3 beta (GSK 3beta) by phosphorylation at serine residue 9 (Ser9). Whilst p53 activation affects cell survival in response to TPEN, GSK-3beta inactivation directly affects glioblastoma cell migration. Therefore, ZIP9 expression could regulate the migratory behavior of glioblastoma cells, so that ZIP9 may be of biological, but not of clinical relevance for glioblastomas, since in GBM tumor tissues, ZIP9 expression is not significantly increased compared to normal brain. PMID- 27654921 TI - Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses. AB - Ocean microbes drive biogeochemical cycling on a global scale. However, this cycling is constrained by viruses that affect community composition, metabolic activity, and evolutionary trajectories. Owing to challenges with the sampling and cultivation of viruses, genome-level viral diversity remains poorly described and grossly understudied, with less than 1% of observed surface-ocean viruses known. Here we assemble complete genomes and large genomic fragments from both surface- and deep-ocean viruses sampled during the Tara Oceans and Malaspina research expeditions, and analyse the resulting 'global ocean virome' dataset to present a global map of abundant, double-stranded DNA viruses complete with genomic and ecological contexts. A total of 15,222 epipelagic and mesopelagic viral populations were identified, comprising 867 viral clusters (defined as approximately genus-level groups). This roughly triples the number of known ocean viral populations and doubles the number of candidate bacterial and archaeal virus genera, providing a near-complete sampling of epipelagic communities at both the population and viral-cluster level. We found that 38 of the 867 viral clusters were locally or globally abundant, together accounting for nearly half of the viral populations in any global ocean virome sample. While two-thirds of these clusters represent newly described viruses lacking any cultivated representative, most could be computationally linked to dominant, ecologically relevant microbial hosts. Moreover, we identified 243 viral-encoded auxiliary metabolic genes, of which only 95 were previously known. Deeper analyses of four of these auxiliary metabolic genes (dsrC, soxYZ, P-II (also known as glnB) and amoC) revealed that abundant viruses may directly manipulate sulfur and nitrogen cycling throughout the epipelagic ocean. This viral catalog and functional analyses provide a necessary foundation for the meaningful integration of viruses into ecosystem models where they act as key players in nutrient cycling and trophic networks. PMID- 27654923 TI - New findings in potential applications of tobacco osmotin. AB - The osmotin protein is involved in both monocot and dicot plant responses to biotic and abiotic stress. To determine the biological activity of osmotin, the gene was amplified from tobacco genomic DNA, fused with the hexahistidine tag motif and successfully expressed in Escherichia coli, after which the recombinant osmotin was purified and renatured. Various activities were then tested, including hemolytic activity, toxicity against human embryonic kidney cells, and the antifungal activity of the recombinant osmotin. We found that osmotin had no adverse effects on human kidney cells up to a concentration of 500 MUg.ml-1. However, the purified osmotin also had significant antimicrobial activity, specifically against fungal pathogens causing candidiasis and otitis, and against the common food pathogens. Using the osmotin-Agrobacterium construct, the osmotin gene was inserted into tobacco plants in order to facilitate the isolation of recombinant protein. Using qPCR, the presence and copy number of the transgene was detected in the tobacco plant DNA. The transgene was also quantified using mRNA, and results indicated a strong expression profile, however the native protein has been never isolated. Once the transgene presence was confirmed, the transgenic tobacco plants were grown in high saline concentrations and monitored for seed germination and chlorophyll content as indicators of overall plant health. Results indicated that the transgenic tobacco plants had a higher tolerance for osmotic stress. These results indicate that the osmotin gene has the potential to increase crop tolerance to stresses such as fungal attack and unfavorable osmotic conditions. PMID- 27654924 TI - Diphenyl diselenide derivatives inhibit microbial biofilm formation involved in wound infection. AB - BACKGROUND: Organoselenium compounds have antimicrobial activity against some bacteria and fungi; furthermore, the antioxidant activity of diselenides has been demonstrated. The aim of the present work was to examine the in vitro minimal inhibitory concentration of a panel of differently substituted diselenides and their effectiveness in inhibiting biofilm formation and dispersing preformed microbial biofilm of Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa and the yeast Candida albicans, all involved in wound infections. Moreover, the cytotoxicity of the compounds was determined in human dermal fibroblast and keratinocytes. In closing, we tested their direct antioxidant activity. RESULTS: Diselenides showed different antimicrobial activity, depending on the microorganism. All diselenides demonstrated a good antibiofilm activity against S. aureus and S. epidermidis, the compounds camphor diselenide, bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] were active against S. pyogenes and C. albicans biofilm while only diselenides 2,2'-diselenidyldibenzoic acid and bis[ethyl-N-(2'-selenobenzoyl) glycinate] were effective against P. aeruginosa. Moreover, the compounds bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] showed an antioxidant activity at concentrations lower than the 50 % of cytotoxic concentration. CONCLUSIONS: Because microbial biofilms are implicated in chronic infection of wounds and treatment failure, the combination of antimicrobial activity and potential radical scavenging effects may contribute to the improvement of wound healing. Therefore, this study suggests that bis[ethylN-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] are promising compounds to be used in preventing and treating microbial wound infections. PMID- 27654925 TI - Prenatal Echocardiographic Assessment of Foramen Ovale Appearance in Fetuses with D-Transposition of the Great Arteries and Impact on Neonatal Outcome. AB - INTRODUCTION: Neonates with D-transposition of the great arteries (dTGA) may die at birth because of the inadequate intracardiac mixing due to a misdiagnosed restrictive foramen ovale. We reviewed our experience in echocardiographic assessment and perinatal management of fetuses with dTGA searching for new features that may predict the need for urgent balloon atrial septostomy (BAS) immediately after birth. PATIENTS AND METHODS: We included fetuses diagnosed with dTGA between January 2000 and December 2014. We assessed pre- and postnatal appearance of the foramen ovale, ductus arteriosus and pulmonary veins. Both the diagnostic findings at the time of last prenatal echocardiogram and those findings deriving from a retrospective reevaluation of stored videos were considered. BAS was defined as urgent if performed in neonates with restrictive foramen ovale and severe hypoxemia. RESULTS: We reviewed 40 fetuses with dTGA. 20/40 fetuses received urgent BAS at birth. Not only the restrictive but also the hypermobile and the redundant appearance of the foramen ovale was significantly associated with urgent BAS (p < 0.0001, p = 0.002 and p = 0.0001, respectively). CONCLUSIONS: Prenatal evaluation of the foramen ovale appearance in fetuses with dTGA is still challenging. Based on our experience, also the redundant foramen ovale appearance may need urgent BAS at birth. PMID- 27654926 TI - Recent advances in complementary and replacement therapy with nutraceuticals in combating gastrointestinal illnesses. AB - The digestive system provides nourishment to the whole body. Disorders in this system would result in many associated illnesses as the body is deprived of essential nutrients. Gastrointestinal diseases, in particular, gastric ulceration, inflammatory bowel diseases and colorectal cancer have become more prevalent in all population age groups. While this can be attributed to diet and lifestyle changes, the measures to combat these illnesses with conventional drugs is losing popularity owing to the harsh side effects, drug resistance and lack of patient compliance. The focus of this review is to endorse promising nutraceutical dietary components such as phytosterols, polyphenols, anthocyanins and polyunsaturated fatty acids and their synergistic value, in combination with conventional management of key gastrointestinal diseases. As most of these nutraceuticals are labile compounds, the need for protection and delivery using a carrier system is stressed and the methods for targeting to specific parts of the gastrointestinal tract are discussed. A section has also been devoted to perspectives on co-encapsulation methods of drugs and nutraceuticals using different particle systems. Multilayered carrier systems like double layered and core shell particles have been proposed as an exemplary system to co-encapsulate both drugs and nutrients while keeping them segregated. PMID- 27654927 TI - Findings in the hair of drug abusers using pressurized liquid extraction and solid-phase extraction coupled in-line with capillary electrophoresis. AB - A suitable method has been developed and validated for simultaneously determining cocaine and its major metabolite, benzoylecgonine, 6-acetylmorphine, codeine, morphine and the methadone enantiomers in human hair samples by the in-line coupling between SPE and CyD-assisted CE with a previous sample pretreatment procedure based on pressurized liquid extraction. Optimal separation was achieved on a fused silica-capillary of 50MUm i.d. and 80cm total length using 11mM alpha CyD in an aqueous solution of 80mM sodium phosphate at pH 2.5 as the separation medium and an applied voltage of 30kV. The SPE-CE device consisted of a short length of capillary packed with Oasis HLB sorbent, which was inserted near to the inlet end of the CE capillary. Several parameters affecting the in-line preconcentration were evaluated. The LOQs reached for hair samples were in the range of 0.3-2.5ng/mg with satisfactory analytical precision in both intraday and day-to-day experiments (RSDs <13%). Relative recoveries greater than 80% were obtained. The method has successfully been applied to the determination of these drugs of abuse in segmented hair from drug abusers who were undergoing methadone maintenance treatment. The results were consistent with the patients' statements, indicating that the method established herein can be used for verifying a history of drug abuse. PMID- 27654929 TI - The Influence of Processing and Storage Conditions on Renal Protein Biomarkers. PMID- 27654930 TI - Effect of Processing Delay and Storage Conditions on Urine Albumin-to-Creatinine Ratio. AB - BACKGROUND AND OBJECTIVES: Because there is substantial biologic intraindividual variation in albumin excretion, randomized trials of albuminuria-reducing therapies may need multiple urine samples to estimate daily urinary albumin excretion. Mailing spot urine samples could offer a convenient and cost-effective method to collect multiple samples, but urine albumin-to-creatinine ratio stability in samples stored at ambient temperatures for several days is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with kidney disease provided fresh urine samples in two tubes (with and without boric acid preservative). Reference aliquots from each participant were analyzed immediately, whereas remaining aliquots were subject to different handling/storage conditions before analysis, including delayed processing for up to 7 days at three different storage temperatures (4 degrees C, 18 degrees C, and 30 degrees C), multiple freeze-thaw cycles, and long-term frozen storage at -80 degrees C, -40 degrees C, and -20 degrees C. We calculated the mean percentage change in urine albumin-to-creatinine ratio for each condition, and we considered samples stable if the 95% confidence interval was within a +/-5% threshold. RESULTS: Ninety-three patients provided samples with detectable albuminuria in the reference aliquot. Median (interquartile range) urine albumin-to-creatinine ratio was 87 (20-499) mg/g. The inclusion of preservative had minimal effect on fresh urine albumin-to-creatinine ratio measurements but reduced the changes in albumin and creatinine in samples subject to processing delay and storage conditions. The urine albumin-to-creatinine ratio was stable for 7 days in samples containing preservative at 4 degrees C and 18 degrees C and 2 days when stored at 30 degrees C. It was also stable in samples with preservative after three freeze-thaw cycles and in frozen storage for 6 months at -80 degrees C or 40 degrees C but not at -20 degrees C. CONCLUSIONS: Mailed urine samples collected with preservative and received within 7 days if ambient temperature is <=18 degrees C, or within 2 days if the temperature is higher but does not exceed 30 degrees C, are suitable for the measurement of urine albumin-to-creatinine ratio in randomized trials. Preserved samples frozen to -40 degrees C or -80 degrees C for 6 months before analysis also seem suitable. PMID- 27654932 TI - Under one roof: The effect of co-residing with adult children on depression in later life. AB - RATIONALE: The number of older parents living without adult children has increased dramatically over the last decades. However, recent trends exacerbated by the Great Recession have led to an increase in intergenerational co-residing. METHODS: We used three waves of data (2004-2010) from the Survey of Health, Ageing and Retirement in Europe (SHARE) collected around the Great Recession to assess the effects of intergenerational co-residence on mental health in later life (n = 50,043). We used an instrumental variable (IV) approach that exploits changes in employment opportunities of adult children during the Great Recession to examine the impact of co-residing with adult children on depression scores measured using the Euro-D scale of depression. RESULTS: Northern European countries exhibited low levels of both co-residence and depression in older age, while most countries in Eastern and Southern Europe had high levels of both co residence and depression. In OLS models that controlled for measured characteristics, co-residing with an adult child was not associated with depressive symptoms in older parents (beta = -0.0387; 95% CI -0.0892 to 0.0118). By contrast, results from IV models suggest that co-residing with an adult child significantly reduces depressive symptoms by 0.731 points (95% CI -1.261 to 0.200) on the 12-item scale. Results were robust to a series of robustness checks including controls for child characteristics, country-specific time trends, and analyses restricted to homeowners. CONCLUSIONS: Our findings suggest that, in the context of high unemployment rates during the Great Recession in Europe, increased intergenerational exchange between adult children and older parents in the form of co-residence had positive mental health effects on older parents. PMID- 27654931 TI - Nocardioides flavus sp. nov., isolated from marine sediment. AB - A Gram-stain-positive, aerobic, non-motile, non-spore-forming and short rod shaped actinomycete strain, Y4T, was isolated from a sediment sample collected from the Western Pacific. This isolate grew in the presence of 0-10 % (w/v) NaCl and at pH 6.0-9.0 and 4-40 degrees C; optimum growth was observed with 1 % (w/v) NaCl and at pH 7.0 and 35-37 degrees C. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain Y4T belonged to the genus Nocardioides and was most closely related to the type strains Nocardioides ganghwensis JC2055T (98.0 %) and Nocardioides exalbidus RC825T (98.0 %), followed by Nocardioides alpinus Cr7-14T (97.9 %), Nocardioides oleivorans DSM 16090T (97.9 %), Nocardioides furvisabuli SBS-26T (97.4 %) and Nocardioides hwasunensis HFW-21T (97.4 %). Sequence similarities between strain Y4T and the other related species of the genus Nocardioides were less than 96.3 %. Strain Y4T had MK-8(H4) and MK-7(H4) as the predominant respiratory quinones and C17 : 1omega8c, iso-C16 : 0 and C17 : 0 as major fatty acids. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, two unknown glycolipids and one unknown lipid. The DNA G+C content was 70.4 mol%. The diagnostic diamino acid in the cell-wall peptidoglycan was ll-diaminopimelic acid. Strain Y4T could be differentiated from recognized Nocardioides species based on phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and DNA-DNA hybridization data. Thus, strain Y4T is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioides flavus sp. nov. is proposed. The type strain is Y4T (=MCCC 1A09944T=LMG 28100T=JCM 19770T=CGMCC 1.12791T). PMID- 27654928 TI - Renal Toxicities of Novel Agents Used for Treatment of Multiple Myeloma. AB - Survival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma. PMID- 27654933 TI - Spontaneous Cerebral Hemorrhage and Sudden Biventricular Failure After Lung Transplantation. PMID- 27654935 TI - An update on minimally invasive techniques in colorectal surgery for neoplasia. AB - Minimally invasive colorectal surgery continues to evolve. As more is learned about the techniques and surgical and oncologic outcomes, practice and technique are modified. It also becomes clear that new technologies do not always provide improved outcomes, especially in novice hands. Therefore, it remains imperative that clinicians understand the benefits and limitations of each minimally invasive technique. The goal remains to decrease the impact of surgery and provide an optimal recovery while remaining diligent to provide optimal functional and oncologic outcomes. PMID- 27654934 TI - Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury. AB - Importance: Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury. Objective: To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury. Design, Settings, and Participants: A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging. Main Outcomes and Measures: Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid beta, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid. Results: A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (rho = 0.58, P = .02 and rho = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-beta levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05). Conclusions and Relevance: Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid beta were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy. PMID- 27654936 TI - Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen. AB - This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named "L-DC" since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties. PMID- 27654938 TI - Erratum to: Adsorption of amino acids on the magnetite-(111)-surface: a force field study. PMID- 27654937 TI - Cancer biomarker discovery is improved by accounting for variability in general levels of drug sensitivity in pre-clinical models. AB - We show that variability in general levels of drug sensitivity in pre-clinical cancer models confounds biomarker discovery. However, using a very large panel of cell lines, each treated with many drugs, we could estimate a general level of sensitivity to all drugs in each cell line. By conditioning on this variable, biomarkers were identified that were more likely to be effective in clinical trials than those identified using a conventional uncorrected approach. We find that differences in general levels of drug sensitivity are driven by biologically relevant processes. We developed a gene expression based method that can be used to correct for this confounder in future studies. PMID- 27654939 TI - Transfer String Kernel for Cross-Context DNA-Protein Binding Prediction. AB - Through sequence-based classification, this paper tries to accurately predict the DNA binding sites of transcription factors (TFs) in an unannotated cellular context. Related methods in the literature fail to perform such predictions accurately, since they do not consider sample distribution shift of sequence segments from an annotated (source) context to an unannotated (target) context. We, therefore, propose a method called "Transfer String Kernel" (TSK) that achieves improved prediction of transcription factor binding site (TFBS) using knowledge transfer via cross-context sample adaptation. TSK maps sequence segments to a high-dimensional feature space using a discriminative mismatch string kernel framework. In this high-dimensional space, labeled examples of the source context are re-weighted so that the revised sample distribution matches the target context more closely. We have experimentally verified TSK for TFBS identifications on fourteen different TFs under a cross-organism setting. We find that TSK consistently outperforms the state-of-the-art TFBS tools, especially when working with TFs whose binding sequences are not conserved across contexts. We also demonstrate the generalizability of TSK by showing its cutting-edge performance on a different set of cross-context tasks for the MHC peptide binding predictions. PMID- 27654941 TI - Machine Learning Algorithms for Automatic Classification of Marmoset Vocalizations. AB - Automatic classification of vocalization type could potentially become a useful tool for acoustic the monitoring of captive colonies of highly vocal primates. However, for classification to be useful in practice, a reliable algorithm that can be successfully trained on small datasets is necessary. In this work, we consider seven different classification algorithms with the goal of finding a robust classifier that can be successfully trained on small datasets. We found good classification performance (accuracy > 0.83 and F1-score > 0.84) using the Optimum Path Forest classifier. Dataset and algorithms are made publicly available. PMID- 27654942 TI - Topographical gradients of semantics and phonology revealed by temporal lobe stimulation. AB - Word retrieval is a fundamental component of oral communication, and it is well established that this function is supported by left temporal cortex. Nevertheless, the specific temporal areas mediating word retrieval and the particular linguistic processes these regions support have not been well delineated. Toward this end, we analyzed over 1000 naming errors induced by left temporal cortical stimulation in epilepsy surgery patients. Errors were primarily semantic (lemon -> "pear"), phonological (horn -> "corn"), non-responses, and delayed responses (correct responses after a delay), and each error type appeared predominantly in a specific region: semantic errors in mid-middle temporal gyrus (TG), phonological errors and delayed responses in middle and posterior superior TG, and non-responses in anterior inferior TG. To the extent that semantic errors, phonological errors and delayed responses reflect disruptions in different processes, our results imply topographical specialization of semantic and phonological processing. Specifically, results revealed an inferior-to superior gradient, with more superior regions associated with phonological processing. Further, errors were increasingly semantically related to targets toward posterior temporal cortex. We speculate that detailed semantic input is needed to support phonological retrieval, and thus, the specificity of semantic input increases progressively toward posterior temporal regions implicated in phonological processing. Hum Brain Mapp 38:688-703, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27654940 TI - Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans. AB - KEY POINTS: Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age. Hypertrophic responses to RET with age are diminished compared to younger individuals. In response to 6 weeks RET, we found blunted hypertrophic responses with age are underpinned by chronic deficits in long-term muscle protein synthesis. We show this is likely to be the result of multifactorial deficits in anabolic hormones and blunted translational efficiency and capacity. These results provide great insight into age-related exercise adaptations and provide a platform on which to devise appropriate nutritional and exercise interventions on a longer term basis. ABSTRACT: Ageing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of 'anabolic resistance' in older humans. Twenty healthy male individuals, 10 younger (Y; 23 +/- 1 years) and 10 older (O; 69 +/- 3 years), performed 6 weeks unilateral RET (6 * 8 repetitions, 75% of one repetition maximum (1-RM), 3 times per week). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2 O (70 atom%; thereafter 50 ml week-1 ), further bilateral VL muscle biopsies were taken at 3 and 6 weeks to quantify muscle protein synthesis (MPS) via gas chromatography-pyrolysis-isotope ratio mass spectrometry. After RET, 1-RM increased in Y (+35 +/- 4%) and O (+25 +/- 3%; P < 0.01), while MVC increased in Y (+21 +/- 5%; P < 0.01) but not O (+6 +/- 3%; not significant (NS)). In comparison to Y, O displayed blunted RET-induced increases in muscle thickness (at 3 and 6 weeks, respectively, Y: +8 +/- 1% and +11 +/- 2%, P < 0.01; O: +2.6 +/- 1% and +3.5 +/- 2%, NS). While 'basal' longer term MPS was identical between Y and O (~1.35 +/- 0.1% day-1 ), MPS increased in response to RET only in Y (3 weeks, Y: 1.61 +/- 0.1% day-1 ; O: 1.49 +/- 0.1% day 1 ). Consistent with this, O exhibited inferior ribosomal biogenesis (RNA:DNA ratio and c-MYC induction: Y: +4 +/- 2 fold change; O: +1.9 +/- 1 fold change), translational efficiency (S6K1 phosphorylation, Y: +10 +/- 4 fold change; O: +4 +/- 2 fold change) and anabolic hormone milieu (testosterone, Y: 367 +/- 19; O: 274 +/- 19 ng dl-1 (all P < 0.05). Anabolic resistance is thus multifactorial. PMID- 27654943 TI - Help-seeking for mental health problems by employees in the Australian Mining Industry. AB - BACKGROUND: The current study examined help-seeking behavior for mental health problems of employees in the mining industry. METHODS: The research involved a paper-based survey completed by a cross-section of employees from eight coalmine sites. The research aimed to investigate the frequency of contact with professional and non-professional sources of support, and to determine the socio demographic and workplace factors associated. RESULTS: A total of 1,457 employees participated, of which, 46.6 % of participants reported contact with support to discuss their own mental health within the preceding 12 months. Hierarchical logistic regression revealed a significant contribution of workplace variables, with job security and satisfaction with work significantly associated with help seeking behavior. CONCLUSIONS: The results provide an insight into the help seeking behaviour of mining employees, providing useful information to guide mental health workplace program development for the mining industry, and male dominated industry more broadly. PMID- 27654944 TI - Dynein-mediated trafficking negatively regulates LET-23 EGFR signaling. AB - Epidermal Growth Factor Receptor (EGFR) signaling is essential for animal development and increased signaling underlies many human cancers. Identifying the genes and cellular processes that regulate EGFR signaling in vivo will help elucidate how this pathway can become inappropriately activated. Caenorhabditis elegans vulva development provides an in vivo model to genetically dissect EGFR signaling. Here we identified a mutation in dhc-1, the heavy chain of the cytoplasmic dynein minus-end directed microtubule motor, in a genetic screen for regulators of EGFR signaling. Despite the many cellular functions of dynein, DHC 1 is a strong negative regulator of EGFR signaling during vulva induction. DHC-1 is required in the signal-receiving cell, genetically functions upstream or in parallel to LET-23 EGFR. LET-23 EGFR accumulates in cytoplasmic foci in dhc-1 mutants consistent with mammalian cell studies whereby dynein has been shown to regulate late endosome trafficking of EGFR with the Rab7 GTPase. However, we found different distributions of LET-23 EGFR foci in rab-7 versus dhc-1 mutants, suggesting that dynein functions at an earlier step of LET-23 EGFR trafficking to the lysosome than RAB-7. Our results demonstrate an in vivo role for dynein in limiting LET-23 EGFR signaling via endosomal trafficking. PMID- 27654947 TI - Sixty seconds on . . . sex education. PMID- 27654945 TI - The tubulin repertoire of C. elegans sensory neurons and its context-dependent role in process outgrowth. AB - Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of alphabeta-tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al., 1999), and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code (Fulton and Simpson, 1976). Here, we use the well-characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question, through genetic dissection of process outgrowth both in vivo and in vitro With single-cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons, and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze process outgrowth and show that four tubulins (tba-1, tba-2, tbb-1, and tbb-2) function partially or fully redundantly, while two others (mec-7 and mec-12) perform specialized, context-dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies between cell types and in vivo and in vitro contexts. PMID- 27654946 TI - A novel method to accurately locate and count large numbers of steps by photobleaching. AB - Photobleaching event counting is a single-molecule fluorescence technique that is increasingly being used to determine the stoichiometry of protein and RNA complexes composed of many subunits in vivo as well as in vitro. By tagging protein or RNA subunits with fluorophores, activating them, and subsequently observing as the fluorophores photobleach, one obtains information on the number of subunits in a complex. The noise properties in a photobleaching time trace depend on the number of active fluorescent subunits. Thus, as fluorophores stochastically photobleach, noise properties of the time trace change stochastically, and these varying noise properties have created a challenge in identifying photobleaching steps in a time trace. Although photobleaching steps are often detected by eye, this method only works for high individual fluorophore emission signal-to-noise ratios and small numbers of fluorophores. With filtering methods or currently available algorithms, it is possible to reliably identify photobleaching steps for up to 20-30 fluorophores and signal-to-noise ratios down to ~1. Here we present a new Bayesian method of counting steps in photobleaching time traces that takes into account stochastic noise variation in addition to complications such as overlapping photobleaching events that may arise from fluorophore interactions, as well as on-off blinking. Our method is capable of detecting >=50 photobleaching steps even for signal-to-noise ratios as low as 0.1, can find up to >=500 steps for more favorable noise profiles, and is computationally inexpensive. PMID- 27654948 TI - Ketoprofen for episodic tension-type headache in adults. AB - BACKGROUND: Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache day per month), frequent episodic TTH (2 to 14 headache days per month), and chronic TTH (15 headache days a month or more). Ketoprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. OBJECTIVES: To assess the efficacy and safety of ketoprofen for treatment of episodic TTH in adults compared with placebo or any active comparator. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Oxford Pain Relief Database up to May 2016, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. SELECTION CRITERIA: We included randomised, double blind, placebo-controlled studies (parallel-group or cross-over) using oral ketoprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral ketoprofen compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included four studies, all of which enrolled adults with frequent episodic TTH. They all specified using the IHS diagnostic criteria and reported mean baseline pain of at least moderate intensity. While 1253 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged one study to be at high risk of bias due to small size.Useful information was available only for ketoprofen 25 mg. For the IHS preferred outcome of being pain-free at two hours the NNT for ketoprofen 25 mg compared with placebo was 9.0 (95% confidence interval (CI) 4.8 to 72) in two studies (272 participants; low quality evidence). The NNT was 3.7 (95% CI 2.6 to 6.3) for pain-free or mild pain at two hours in two studies (272 participants; moderate quality evidence). Fewer people needed rescue medication with ketoprofen 25 mg than with placebo, with a number needed to treat to prevent one event (NNTp) of 6.2 (95% CI 4.3 to 11) in three studies (605 participants; moderate quality evidence). The number of participants reporting any adverse event was higher with ketoprofen 25 mg than placebo (NNH 15, (95% CI 8.7 to 45)) in three studies (651 participants with 66 events; low quality evidence). Most events were of mild to moderate intensity.Ketoprofen 25 mg was not different from paracetamol 1000 mg in two studies with 276 participants for any efficacy outcomes (low to moderate quality evidence); the RR for pain-free at two hours was 1.3 (95% CI 0.9 to 2.0). The number of participants reporting any adverse event was higher with ketoprofen 25 mg than with paracetamol (NNH 17, 95% CI 8.9 to 130)) in two studies (582 participants, 68 events; low quality evidence).Studies reported no serious adverse events.We judged the quality of the evidence comparing ketoprofen 25 mg with placebo or paracetamol 1000 mg as moderate to very low. Where evidence was downgraded it was because of the small number of studies and events. AUTHORS' CONCLUSIONS: Ketoprofen 25 mg provided a small benefit compared with placebo in terms of being pain-free at two hours or having mild or no pain at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity. Its use was associated with more people experiencing adverse events. Ketoprofen 25 mg was not superior to paracetamol 1000 mg for any efficacy outcome. PMID- 27654949 TI - Measurement of emerging dechloranes in human serum using modulated gas chromatography coupled to electron capture negative ionization time-of-flight mass spectrometry. AB - RATIONALE: Quite recently, the presence of significant amounts of several emerging Dechlorane (Dec) flame retardants (FRs) was reported in environmental and biota samples, principally from Canada and China, but also from Europe. Several molecules were identified, e.g. Dec 602, 603, 604, Dechlorane Plus (DP), and Chlordene Plus (CP). Gas chromatography (GC) coupled to electron ionization (EI) high-resolution mass spectrometry (HRMS) is typically used for their measurement in various matrices based on hexachlorocyclopentadiene (HCCPD) fragment ions at m/z 271.8102/273.8072. METHODS: We investigated the use of GC with cryogenic zone compression and electron capture negative ionization time-of flight mass spectrometry (CZC-GC/ECNI-TOFMS) to measure Dechlorane compounds at low levels in human serum. The TOFMS instrument provided a resolving power of 5000 (FWHM) with an acquisition rate of 25 Hz and was equipped with a specific low thermal emission filament, which allowed it to perform reproducibly in ECNI mode at ion source temperatures as low as 140 degrees C, thus yielding a signal for the molecular ion cluster. RESULTS: The method provided comparable sensitivity to the GC/EI-SectorHRMS technique used in selected ion monitoring (SIM) mode, and specificity for the target Dechlorane compounds. The method was applied on human serum samples and quantification was performed for Dec 602, Dec 603, and CP, ranging from 0.1 to 10 ng/g lipid weight levels. The main drawbacks of the method are the high instrument detection limits (IDLs) obtained for DP and Dec 604. The method would benefit from even softer ionization and better ion transmission. CONCLUSIONS: The main advantages of the present method are the selectivity, as detection is based on the molecular ion signal, and the use of good mass accuracy combined with isotopic distribution calculation for molecular formulae investigation of halogenated compounds. This methodology should facilitate the monitoring of emerging Dechlorane contaminants in future studies, and possibly extend the scope to untargeted emerging analogues. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27654950 TI - Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment. AB - BACKROUND: In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. METHODS: Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. RESULTS: A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. CONCLUSIONS: The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. PMID- 27654951 TI - Disruption of Src homology 3-binding motif within non-structural protein 1 of influenza B virus unexpectedly enhances viral replication in human cells. AB - The influenza virus non-structural protein 1 (NS1) is a multifunctional virulence factor that plays a crucial role during infection by blocking the innate antiviral immune response of infected cells. In contrast to the well-studied NS1 protein of influenza A virus, knowledge about structure and functions of the influenza B virus homologue B/NS1, which shares less than 25 % sequence identity, is still limited. Here, we report on a reverse genetic analysis to study the role of a highly conserved class II Src homology 3 domain-binding motif matching the consensus PxxPx(K/R) that we identified at positions 122-127 of the B/NS1 protein. Surprisingly, glycine substitutions in the Src homology 3 domain-binding motif increased virus replication up to three orders of magnitude in human lung cells. Enhanced mutant virus propagation was accompanied by increased gene expression and apoptosis induction linking this motif to the control of programmed cell death. A MS-based interactome study revealed that the glycine substitutions facilitate binding of B/NS1 to heat shock protein 90-beta (HSP90beta). Moreover, recruitment of the viral polymerase basic protein 2 to the B/NS1-HSP90beta complex was observed. Pharmacological inhibition of HSP90 reduced mutant virus propagation suggesting that the mutation-induced involvement of HSP90beta enhanced viral replication. This study not only functionally characterizes a conserved motif within the B/NS1 protein, but also illustrates a rare example in which mutation of a highly conserved sequence within a viral protein does not result in high fitness costs, but rather increases viral replication via recruitment of a host factor. PMID- 27654952 TI - Increased pCO2 and temperature reveal ecotypic differences in growth and photosynthetic performance of temperate and Arctic populations of Saccharina latissima. AB - MAIN CONCLUSION: The Arctic population of the kelp Saccharina latissima differs from the Helgoland population in its sensitivity to changing temperature and CO 2 levels. The Arctic population does more likely benefit from the upcoming environmental scenario than its Atlantic counterpart. The previous research demonstrated that warming and ocean acidification (OA) affect the biochemical composition of Arctic (Spitsbergen; SP) and cold-temperate (Helgoland; HL) Saccharina latissima differently, suggesting ecotypic differentiation. This study analyses the responses to different partial pressures of CO2 (380, 800, and 1500 uatm pCO2) and temperature levels (SP population: 4, 10 degrees C; HL population: 10, 17 degrees C) on the photophysiology (O2 production, pigment composition, D1-protein content) and carbon assimilation [Rubisco content, carbon concentrating mechanisms (CCMs), growth rate] of both ecotypes. Elevated temperatures stimulated O2 production in both populations, and also led to an increase in pigment content and a deactivation of CCMs, as indicated by 13C isotopic discrimination of algal biomass (epsilon p) in the HL population, which was not observed in SP thalli. In general, pCO2 effects were less pronounced than temperature effects. High pCO2 deactivated CCMs in both populations and produced a decrease in the Rubisco content of HL thalli, while it was unaltered in SP population. As a result, the growth rate of the Arctic ecotype increased at elevated pCO2 and higher temperatures and it remained unchanged in the HL population. Ecotypic differentiation was revealed by a significantly higher O2 production rate and an increase in Chl a, Rubisco, and D1 protein content in SP thalli, but a lower growth rate, in comparison to the HL population. We conclude that both populations differ in their sensitivity to changing temperatures and OA and that the Arctic population is more likely to benefit from the upcoming environmental scenario than its Atlantic counterpart. PMID- 27654953 TI - Trichoscopy as a useful method to differentiate tinea capitis from alopecia areata in children at Zagazig University Hospitals. AB - Trichoscopy corresponds to the scalp, and hair dermoscopy has been increasingly used as an aid in the diagnosis, follow-up, and prognosis of hair disorders. Trichoscopy represents a valuable link between clinical and histological diagnosis. Tinea capitis (TC) and alopecia areata (AA) are considered the most common causes of hairless patches of the scalp in pediatrics. TC may have the same clinical appearance of AA, so dermoscopy has recently become a useful diagnostic tool for AA and TC, particularly in doubtful cases. The aim of this study is to identify the trichoscopic features of TC and AA in children that may facilitate in their differentiation from each other and choosing the appropriate treatment, which is a non-invasive method of diagnosis. PMID- 27654954 TI - Residue depletion of amoxicillin and its major metabolites in eggs. AB - The depletion of amoxicillin (AMO) and its major metabolites, amoxicilloic acid (AMA) and amoxicillin-diketopiperazine-2',5'-dione (DIKETO) in the albumen, yolk and whole egg was studied after the oral dose of AMO (25 and 50 mg/kg body weight) to laying hens once per day for five consecutive days. Egg samples were prepared by a simple liquid-liquid extraction procedure with acetonitrile and saturated methylene chloride and analysed using liquid chromatography-tandem mass spectrometry. The results showed that AMO, AMA and DIKETO residues were mainly distributed in the yolk, where particularly high concentrations of AMO and DIKETO were found, whereas the albumen contained high concentrations of AMA. This distribution suggested that AMO and DIKETO were depleted slowly in yolk, whereas AMA was depleted slowly in albumen. The amount of AMO residue positively correlated with the dose, and the theoretical withdrawal times, which were calculated based on the residue level falling below a safe limit, were 5.21 and 7.67 days at AMO doses of 25 and 50 mg/kg, respectively. Moreover, the theoretical withdrawal times for all residues in the whole egg were 8.00 and 9.11 days at doses of 25 and 50 mg/kg, respectively. Our findings suggested that 9 days was an appropriate withdrawal time for the use of AMO in laying hens. PMID- 27654955 TI - Natural history of superficial head and neck squamous cell carcinoma under scheduled follow-up endoscopic observation with narrow band imaging: retrospective cohort study. AB - BACKGROUND: The incidence rate has been increasing for superficial head and neck squamous cell carcinoma (HNSCC) discovered through surveillance endoscopic study using narrow band imaging (NBI), a procedure mainly used for high-risk patients with esophageal squamous cell carcinoma (ESCC). However, there are few reports on the natural history of superficial HNSCC. The aim of this retrospective study was to investigate the natural history of superficial HNSCC. METHODS: From January 2007 to December 2012, 535 consecutive histologically confirmed superficial HNSCCs at the oropharynx, hypopharynx, or larynx in 319 patients were detected by endoscopic surveillance examination by using NBI. Of those, 20 untreated and observed lesions fulfilled the eligibility criteria and were analyzed in this study. RESULTS: Twenty lesions from 17 patients were analyzed. All patients were men ranging from 52 to 86 years of age, with a median age of 69 years. The median endoscopic follow-up period was 20 months (range, 6-71); 17 lesions progressed in size. In this study, four patients died; the causes of death were synchronous ESCC, synchronous HNSCC, acute myocardial infarction, and unknown causes. No patient died from progression of superficial HNSCC. CONCLUSIONS: Most superficial HNSCC has the potential to change progressively. Therefore, superficial HNSCC should be detected at an early stage and be treated less invasively, such as with endoscopic resection or partial resection. PMID- 27654956 TI - Mixed Directing-Group Strategy: Oxidative C-H/C-H Bond Arylation of Unactivated Arenes by Cobalt Catalysis. AB - A mixed directing-group strategy for inexpensive [Co(acac)3 ]-catalyzed oxidative C-H/C-H bond arylation of unactivated arenes has been disclosed. This strategy enables the arylation of a wide range of benzamide and arylpyridines effectively to afford novel bifunctionalized biaryls, which are difficult to achieve by common synthetic routes. Two different pathways, namely, a single-electron transmetalation process (8-aminoquinoline-directed) and a concerted metalation deprotonation process (pyridine-directed), were involved to activate two different inert aromatic C-H bonds. Moreover, the aryl radicals have been trapped by 2,6-di-tert-butyl-4-methylphenol to form benzylated products. This unique strategy should be useful in the design of other arene C-H/C-H cross-couplings as well. PMID- 27654957 TI - Predictors of psychological improvement on non-professional suicide message boards: content analysis. AB - BACKGROUND: Suicide message boards have been at the core of debates about negative influences of the Internet on suicidality. Nothing is currently known about communication styles that may help users to psychologically improve in these settings. METHOD: In all, 1182 archival threads with 20 499 individual postings from seven non-professional suicide message boards supporting an 'against-suicide', 'neutral' or 'pro-suicide' attitude were randomly selected and subject to content analysis. Initial needs of primary posters (i.e. individual who open a thread), their psychological improvement by the end of the thread, their responses received and indicators of suicidality were coded. Differences between 'pro-suicide', 'neutral' and 'against suicide' boards, and correlations between primary posters and respondents in terms of suicidality were assessed. Logistic regression was used to test associations with psychological improvement. RESULTS: 'Pro-suicide' boards (n = 4) differed from 'neutral' (n = 1) and 'against-suicide' (n = 2) boards in terms of communicated contents. Indicators of suicidality correlated moderately to strongly between primary posters and respondents on 'pro-suicide' message boards, but less on other boards. Several communicative strategies were associated with psychological improvement in primary posters, including the provision of constructive advice [adjusted odds ratio (aOR) 4.10, 95% confidence interval (CI) 2.40-7.03], active listening (aOR 1.60, 95% CI 1.12-2.27), sympathy towards the poster (aOR 2.22, 95% CI 1.68-2.95) and provision of alternatives to suicide (aOR 2.30, 95% CI 1.67-3.18). CONCLUSIONS: Respondents resemble primary posters with regard to suicidality in 'pro-suicide' boards, which may hinder psychological improvement. Still, opportunities to intervene in these settings using simple communication techniques exist and need to be taken and evaluated. PMID- 27654958 TI - Household adjustment to flood risk: a survey of coastal residents in Texas and Florida, United States. AB - Individual households have increasingly borne responsibility for reducing the adverse impacts of flooding on their property. Little observational research has been conducted, however, at the household level to examine the major factors contributing to the selection of a particular household adjustment. This study addresses the issue by evaluating statistically the factors influencing the adoption of various household flood hazard adjustments. The results indicate that respondents with higher-value homes or longer housing tenure are more likely to adopt structural and expensive techniques. In addition, the information source and the Community Rating System (CRS) score for the jurisdiction where the household is located have a significant bearing on household adjustment. In contrast, proximity to risk zones and risk perception yield somewhat mixed results or behave counter to assumptions in the literature. The study findings provide insights that will be of value to governments and decision-makers interested in encouraging homeowners to take protective action given increasing flood risk. PMID- 27654959 TI - DNase gamma, DNase I and caspase-activated DNase cooperate to degrade dead cells. AB - Serum endonucleases are essential for degrading the chromatin released from dead cells and preventing autoimmune diseases such as systemic lupus erythematosus. Serum DNase I is known as the major endonuclease, but recently, another endonuclease, DNase gamma/DNase I-like 3, gained attention. However, the precise role of each endonuclease, especially that of DNase gamma, remains unclear. In this study, we distinguished the activities of DNase gamma from those of DNase I in mouse serum and concluded that both cooperated in degrading DNA during necrosis: DNase gamma functions as the primary chromatolytic activity, causing internucleosomal DNA fragmentation, and DNase I as the secondary one, causing random DNA digestion for its complete degradation. These results were confirmed by two in vivo experimental mouse models, in which necrosis was induced, acetaminophen-induced hepatic injury and streptozotocin-induced beta-cell necrosis models. We also determined that DNase gamma functions as a backup endonuclease for caspase-activated DNase (CAD) in the secondary necrosis phase after gamma-ray-induced apoptosis in vivo. PMID- 27654961 TI - Doctor please feel my pulses! An aid to diagnosis in the newborn. PMID- 27654960 TI - In vivo study of alginate hydrogel conglutinating cells to polycaprolactone vascular scaffolds fabricated by electrospinning. AB - OBJECTIVE: The aim of this study was to explore an innovative cell-seeding technology applied on artificial vascular scaffolds. METHODS: Scaffolds were fabricated by electrospinning polycaprolactone (PCL) and seeded with rat endothelial progenitor cells differentiated from adipose-derived stem cells. Then, we modified the PCL scaffolds through the use of alginate hydrogel conglutinating cells (AHCC), a blank alginate hydrogel coating (BAHC), and natural sedimentation seeding cells (NSSC). The blank PCL (BP) scaffolds without any modifications were considered the blank control group. After modification, the scaffolds were implanted in a rat model. The implanted scaffolds were harvested and observed using histological and immunohistochemical methods and scanning electron microscopy (SEM) at 1, 2, and 4 weeks after implantation, respectively. RESULTS: The best regeneration and configuration of the endothelium tissue and the most similar morphology to that of natural endangium was observed qualitatively in the AHCC scaffolds. The BP scaffolds had qualitatively the worst regeneration and configuration and the most dissimilar morphology at the same time point. In the AHCC group, cells could adhere directly on the inner surface of the vascular scaffolds, eliminating the time delay via the NSSC method prior to cell adhesion. CONCLUSION: AHCC are an effective method for seeding cells on vascular scaffolds and can eliminate the time delay for cell adhesion. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2443 2454, 2017. PMID- 27654962 TI - Vector Competence of French Polynesian Aedes aegypti and Aedes polynesiensis for Zika Virus. AB - BACKGROUND: In 2013-2014, French Polynesia experienced for the first time a Zika outbreak. Two Aedes mosquitoes may have contributed to Zika virus (ZIKV) transmission in French Polynesia: the worldwide distributed Ae. aegypti and the Polynesian islands-endemic Ae. polynesiensis mosquito. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate their vector competence for ZIKV, mosquitoes were infected per os at viral titers of 7 logs tissue culture infectious dose 50%. At several days post-infection (dpi), saliva was collected from each mosquito and inoculated onto C6/36 mosquito cells to check for the presence of ZIKV infectious particles. Legs and body of each mosquito were also collected and submitted separately to RNA extraction and ZIKV RT-PCR. In Ae. aegypti the infection rate was high as early as 6 dpi and the dissemination efficiency get substantial from 9 dpi while the both rates remained quite low in Ae. polynesiensis. The transmission efficiency was poor in Ae. aegypti until 14 dpi and no infectious saliva was found in Ae. polynesiensis at the time points studied. CONCLUSIONS/SIGNIFICANCE: In our experimental conditions, the late ability of the French Polynesian Ae. aegypti to transmit ZIKV added by the poor competence of Ae. polynesiensis for this virus suggest the possible contribution of another vector for the propagation of ZIKV during the outbreak, in particular in remote islands where Ae. polynesiensis is predominating. PMID- 27654963 TI - Interleukin-1 is not involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis. AB - OBJECTIVE: Interleukin-1 (IL-1) is an alleged important cytokine in osteoarthritis (OA), although the exact contribution of IL-1 to joint destruction remains unclear. Here we investigated the involvement of IL-1alpha and IL-1beta in joint pathology during collagenase-induced OA (CiOA). METHODS: CiOA was induced in wild type (WT) and IL-1alphabeta-/- mice. Additionally, IL-1 signaling was inhibited in WT mice with CiOA using osmotic pumps containing IL-1RA. Joint pathology was assessed using histology. Activity of cartilage-degrading enzymes was determined using antibodies against aggrecan neo-epitopes VDIPEN and NITEGE. Synovial gene expression was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Serum protein levels were measured with Luminex or enzyme-linked immunosorbent assay (ELISA). RESULTS: Synovial IL-1beta expression was strongly elevated 7 days after induction of CiOA in WT mice but decreased afterwards, whereas S100A8/A9, previously described to aggravate OA, remained elevated for 21 days. Remarkably, synovial inflammation was comparable between WT and IL-1alphabeta-/- mice on day 7 of CiOA. In line, synovial mRNA expression of genes involved in IL-1 signaling and inflammatory mediators was comparable between WT and IL-1alphabeta-/- mice, and serum levels for Keratinocyte Chemoattractant (KC)/IL-6/S100A8/S100A9/IL-10 were equal. Synovial matrix metalloproteinase (MMP)/aggrecanase expression and activity in cartilage was not different in WT and IL-1alphabeta-/- mice on day 7 of CiOA. Cartilage destruction on day 42 was not different between WT and IL-1alphabeta-/- mice, which was supported by our finding that IL-1RA treatment in WT mice with CiOA did not alter joint destruction. CONCLUSIONS: IL-1alpha and IL-1beta are not involved in synovial inflammation and cartilage destruction during CiOA, implicating that other mediators are responsible for the joint damage. PMID- 27654964 TI - Concentrations of synovial fluid biomarkers and the prediction of knee osteoarthritis 16 years after anterior cruciate ligament injury. AB - OBJECTIVE: To describe the longitudinal patterns of release, and investigate the association between a set of synovial fluid biomarkers at the acute and chronic stage and the development of radiographic knee osteoarthritis (OA) after an anterior cruciate ligament (ACL) injury. DESIGN: Synovial fluid was aspirated from the acutely ACL-injured knee within the first 2weeks (acute samples), and yearly (chronic samples) up to 7.5 years after injury in 88 subjects (60% men). Non-injured subjects (n = 12) were used as reference group. Aggrecan, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 in synovial fluid were quantified by immunoassays. The presence of radiographic tibiofemoral (TF) or patellofemoral (PF) OA [Kellgren and Lawrence (K&L) >=2] was examined with weight-bearing knee radiography 16 years after the ACL injury. RESULTS: The average acute and chronic SF concentrations of COMP and aggrecan were elevated in comparison with the reference group (P < 0.001). The levels of COMP and aggrecan clearly decreased approximately half a year after the ACL injury, and returned to reference values during the 7.5 years of follow-up. Using logistic regression analysis neither acute nor chronic concentrations of the four biomarkers were associated with the development of radiographic knee OA at the 16 year follow-up. CONCLUSION: Increased synovial fluid concentrations of aggrecan and COMP was related to knee injury, but acute and chronic synovial fluid concentrations of aggrecan, COMP, MMP-3 and TIMP-1 failed to predict knee OA 16 years after ACL injury. PMID- 27654965 TI - Soluble (Pro) Renin Receptor is a Predictor of Gestational Diabetes Mellitus. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is a common endocrine complication in pregnancy. While it has been established that age, family history of diabetes, insulin resistance and several biomarkers are associated with GDM but significant gaps remain in understanding risk factors for GDM. Soluble pro renin receptor (s [Pro] RR) as a biomarker reflects the activation of renin angiotensin system in tissues which may be related to insulin resistance Objective: The aim of this study was to determine the role of (s [pro] RR) in predicting GDM. METHODS: one hundred-eighty singleton pregnant women in first trimester were enrolled. We excluded women with previous history of GDM, hypertension and consumption of drugs affected reninangiotensin system. A fasting blood glucose and s (pro) RR level were obtained during first trimester and OGTT was performed at 24-28 weeks of gestation. We used ROC curves to identify s (pro) RR cutoff points for detecting GDM and the difference in s (pro)RR level was assessed in GDM and non- GDM women. RESULTS: Among 180 women, 24 (13.33%) had GDM. There was no significant difference between age and body mass index in subjects with GDM compared to non- GDM. The concentration of s (pro) RR was significantly higher in GDM subjects rather than non- GDM [29.27(24.60-35.92) vs. 22.89(19.46- 24.27), P<0.001]. Multiple logistic regression analysis revealed a significant association of s(pro) RR with GDM (odd ratio: 1.32, 95% CI: 1.17 1.48, P=0.04). A cut-off point 24.52 ng/ml of s(pro) RR had 75% sensitivity and 80% specificity for predicting GDM. CONCLUSION: Increased level of s (pro) RR in first trimester may be a marker for predicting GDM. PMID- 27654966 TI - Marijuana and tobacco co-administration in blunts, spliffs, and mulled cigarettes: A systematic literature review. AB - BACKGROUND: Blunts and spliffs/mulled cigarettes combine marijuana and tobacco for co-administration (use at the same time, in the same product). Co administration of marijuana and tobacco presents significant potential for nicotine exposure, and may lead to exclusive tobacco use patterns, nicotine addiction, and compounded health effects. No review articles have summarized the number and nature of studies published on these co-administered products. METHODS: Keywords "(blunt* OR spliff OR mull* OR joint) AND (tobacco OR smok* OR cigarette) AND (cannabis OR marijuana OR hashish)" were searched in the published literature. A total of 220 articles were considered for inclusion, 49 were reviewed by two independent qualitative coders, and 45 were included in this review. RESULTS: Of the 45 articles, most (n=27) of studies were observational or descriptive; ten were qualitative, five employed causal designs, and three were mixed methods. A majority of the studies assessed blunts; only 11 studies assessed spliffs/mulled cigarettes. Many studies focused on sub-populations of youth, males, and African Americans. Use of co-administered marijuana and tobacco products was associated with several indicators of problematic use patterns, including perceptions of less risk, dependence on nicotine and marijuana, and greater subjective effects related to marijuana. CONCLUSIONS: Literature on marijuana and tobacco co-administration comes largely from qualitative and observational/descriptive studies. In addition to continued surveillance, experimental research that directly assesses the smoking patterns of co administered marijuana and tobacco products as compared with to those of marijuana and tobacco only products is needed to determine the potential long term health consequences of using blunts, spliffs, or other co-administered products. PMID- 27654967 TI - Erratum to: The Rho kinase inhibitor, fasudil, ameliorates diabetes-induced cardiac dysfunction by improving calcium clearance and actin remodeling. PMID- 27654968 TI - Tau Positron Emission Tomographic Imaging in the Lewy Body Diseases. AB - Importance: The causes of cognitive impairment in dementia with Lewy bodies (DLB) and Parkinson disease (PD) are multifactorial. Tau pathologic changes are commonly observed at autopsy in individuals with DLB and PD dementia, but their contribution to these diseases during life is unknown. Objective: To contrast tau aggregation in DLB, cognitively impaired persons with PD (PD-impaired), cognitively normal individuals with PD (PD-normal), and healthy persons serving as control participants, and to evaluate the association between tau aggregation, amyloid deposition, and cognitive function. Design, Setting, and Participants: This cross-sectional study was conducted from January 1, 2014, to April 28, 2016, in a tertiary care center's memory and movement disorders units. Twenty-four patients with Lewy body disease (7 DLB, 8 PD-impaired, and 9 PD-normal) underwent multimodal brain imaging, cognitive testing, and neurologic evaluation, and imaging measures were compared with those of an independently acquired group of 29 controls with minimal brain amyloid burden as measured with carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET). Exposures: Imaging with fluorine 18-labeled AV-1451 ([18F]AV-1451) (formerly known as [18F]T807), [11C]PiB PET, magnetic resonance imaging (MRI), neurologic examination, and detailed cognitive testing using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale. Main Outcomes and Measures: Main outcomes were differentiation of diagnostic groups on the basis of [18F]AV-1451 binding, the association of [18F]AV-1451 binding with [11C]PiB binding, and the association of [18F]AV-1451 binding with cognitive impairment. All but 3 individuals underwent amyloid imaging with [11C]PiB PET. The hypotheses being tested were formulated before data collection. Mini-Mental State Examination (range, 0-30, with 30 being best) and Clinical Dementia Rating scale sum-of-boxes scale (range, 0-18, with 0 being best) were used for assessment of cognitive function. Results: In patients with DLB, cortical [18F]AV-1451 uptake was highly variable and greater than in the controls, particularly in the inferior temporal gyrus and precuneus. Foci of increased [18F]AV-1451 binding in the inferior temporal gyrus and precuneus were also evident in PD-impaired patients. Elevated cortical [18F]AV-1451 binding was observed in 4 of 17 patients with Lewy body disease with low cortical [11C]PiB retention. For DLB and PD impaired patients, greater [18F]AV-1451 uptake in the inferior temporal gyrus and precuneus was associated with increased cognitive impairment as measured with the MMSE and the Clinical Dementia Rating scale sum-of-boxes score. Conclusions and Relevance: Patients with Lewy body disease manifest a spectrum of tau pathology. Cortical aggregates of tau are common in patients with DLB and in PD-impaired patients, even in those without elevated amyloid levels. When present, tau deposition is associated with cognitive impairment. These findings support a role for tau copathology in the Lewy body diseases. PMID- 27654969 TI - Docosahexaenoic Acid Inhibits Tumor Promoter-Induced Urokinase-Type Plasminogen Activator Receptor by Suppressing PKCdelta- and MAPKs-Mediated Pathways in ECV304 Human Endothelial Cells. AB - The overexpression of urokinase-type plasminogen activator receptor (uPAR) is associated with inflammation and virtually all human cancers. Despite the fact that docosahexaenoic acid (DHA) has been reported to possess anti-inflammatory and anti-tumor properties, the negative regulation of uPAR by DHA is still undefined. Here, we investigated the effect of DHA on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced uPAR expression and the underlying molecular mechanisms in ECV304 human endothelial cells. DHA concentration-dependently inhibited TPA induced uPAR. Specific inhibitors and mutagenesis studies showed that PKCdelta, JNK1/2, Erk1/2, NF-kappaB, and AP-1 were critical for TPA-induced uPAR expression. Application of DHA suppressed TPA-induced translocation of PKCdelta, activation of the JNK1/2 and Erk1/2 signaling pathways, and subsequent AP-1 and NF-kappaB transactivation. In conclusion, these observations suggest a novel role for DHA in reducing uPAR expression and cell invasion by inhibition of PKCdelta, JNK1/2, and Erk1/2, and the reduction of AP-1 and NF-kappaB activation in ECV304 human endothelial cells. PMID- 27654971 TI - Inhibition of EGFR, HER2, and HER3 signaling with AZD8931 in combination with anastrozole as an anticancer approach: Phase II randomized study in women with endocrine-therapy-naive advanced breast cancer. AB - PURPOSE: AZD8931 is an orally bioavailable, reversible tyrosine kinase inhibitor of EGFR, HER2, and HER3 signaling. The Phase II MINT study (ClinicalTrials.gov NCT01151215) investigated whether adding AZD8931 to endocrine therapy would delay development of endocrine resistance in patients with hormone-sensitive advanced breast cancer. METHODS: Patients were randomized 1:1:1 to receive daily anastrozole (1 mg) in combination with AZD8931 20 mg twice daily (bid), AZD8931 40 mg bid, or placebo. The primary objective was evaluation of progression-free survival (PFS) in patients treated with combination AZD8931 and anastrozole versus anastrozole alone. Secondary objectives included assessment of safety and tolerability, objective response rate, and overall survival. RESULTS: At the interim analysis, 359 patients were randomized and received anastrozole in combination with AZD8931 20 mg (n = 118), 40 mg (n = 120), or placebo (n = 121); 39 % of patients (n = 141) had a progression event. Median PFS (HR; 95 % CI vs placebo) in the AZD8931 20, 40 mg, and placebo arms was 10.9 (1.37; 0.91-2.06, P = 0.135), 13.8 (1.16; 0.77-1.75, P = 0.485), and 14.0 months, respectively. No indication of clinical benefit was observed following treatment with AZD8931 for the secondary endpoints. Safety findings showed a greater incidence of diarrhea (40, 51, and 12 % for AZD8931 20, 40 mg, and placebo, respectively), rash (32, 48, and 12 %), dry skin (19, 25, and 2 %), and acneiform dermatitis (16, 28, and 2 %) in patients treated with AZD8931 versus placebo. CONCLUSIONS: AZD8931, in combination with endocrine therapy, does not appear to enhance endocrine responsiveness and is associated with greater skin and gastrointestinal toxicity. PMID- 27654970 TI - Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States. AB - PURPOSE: Based on available phase III trial data, we performed a cost effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). PATIENTS AND METHODS: We constructed a Markov model to assess the cost effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. RESULTS: The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy. CONCLUSION: Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy. PMID- 27654975 TI - Clinical Outcome Prediction Using Single-Cell Data. AB - Single-cell technologies like flow cytometry (FCM) provide valuable biological data for knowledge discovery in complex cellular systems like tissues and organs. FCM data contains multi-dimensional information about the cellular heterogeneity of intricate cellular systems. It is possible to correlate single-cell markers with phenotypic properties of those systems. Cell population identification and clinical outcome prediction from single-cell measurements are challenging problems in the field of single cell analysis. In this paper, we propose a hybrid learning approach to predict clinical outcome using samples' single-cell FCM data. The proposed method is efficient in both i) identification of cellular clusters in each sample's FCM data and ii) predict clinical outcome (healthy versus unhealthy) for each subject. Our method is robust and the experimental results indicate promising performance. PMID- 27654972 TI - Interferon-gamma blocks signalling through PDGFRbeta in human brain pericytes. AB - BACKGROUND: Neuroinflammation and blood-brain barrier (BBB) disruption are common features of many brain disorders, including Alzheimer's disease, epilepsy, and motor neuron disease. Inflammation is thought to be a driver of BBB breakdown, but the underlying mechanisms for this are unclear. Brain pericytes are critical cells for maintaining the BBB and are immunologically active. We sought to test the hypothesis that inflammation regulates the BBB by altering pericyte biology. METHODS: We exposed primary adult human brain pericytes to chronic interferon gamma (IFNgamma) for 4 days and measured associated functional aspects of pericyte biology. Specifically, we examined the influence of inflammation on platelet-derived growth factor receptor-beta (PDGFRbeta) expression and signalling, as well as pericyte proliferation and migration by qRT-PCR, immunocytochemistry, flow cytometry, and western blotting. RESULTS: Chronic IFNgamma treatment had marked effects on pericyte biology most notably through the PDGFRbeta, by enhancing agonist (PDGF-BB)-induced receptor phosphorylation, internalization, and subsequent degradation. Functionally, chronic IFNgamma prevented PDGF-BB-mediated pericyte proliferation and migration. CONCLUSIONS: Because PDGFRbeta is critical for pericyte function and its removal leads to BBB leakage, our results pinpoint a mechanism linking chronic brain inflammation to BBB dysfunction. PMID- 27654976 TI - A Wirelessly-Powered Homecage With Segmented Copper Foils and Closed-Loop Power Control. AB - A new wireless electrophysiology data acquisition system, built around a standard homecage, is presented in this paper, which can power up and communicate with sensors and actuators/stimulators attached to or implanted in small freely behaving animal subjects, such as rodents. Key abilities of the energized homecage (EnerCage) system is enabling longitudinal experiments with minimal operator involvement or interruption, while providing test subjects with an enriched environment closer to their natural habitat, without the burden of being tethered or carrying bulky batteries. The magnetic resonant multi-coil design used in the new EnerCage-HC2 automatically localizes the transmitted electromagnetic power from a single transmitter (Tx) coil at the bottom of the cage toward the receiver coil (Rx), carried on/in the animal body, obviating the need for tracking the animal or switching the coils. In order to increase the resonators' quality factor (Q > 166) at the desired operating frequency of 13.56 MHz, while maintaining a high self-resonance frequency [Formula: see text], they are made of wide copper foils and optimally segmented based on a set of design rules that can be adopted for experimental arenas with different shapes and dimensions. The Rx rectified voltage is regulated at a user-defined window [Formula: see text] by a Tx-Rx closed-loop power control (CLPC) mechanism that creates a volume inside the homecage with 42 mW of power delivered to the load (PDL), and a homogeneous power transfer efficiency (PTE) plane of 14% on average at ~7 cm height, plus stability against angular mis-alignments of up to 80 degrees . PMID- 27654977 TI - An Integrated Passive Phase-Shift Keying Modulator for Biomedical Implants With Power Telemetry Over a Single Inductive Link. AB - This paper presents a passive phase-shift keying (PPSK) modulator for uplink data transmission for biomedical implants with simultaneous power and data transmission over a single 13.56 MHz inductive link. The PPSK modulator provides a data rate up to 1.35 Mbps with a modulation index between 3% and 38% for a variation of the coupling coefficient between 0.05 and 0.26. This modulation scheme is particularly suited for biomedical implants that have high power demand and low coupling coefficients. The PPSK modulator operates in conjunction with on off-keying downlink communication. The same inductive link is used to provide up to 100 mW of power to a multi-channel stimulator. The majority of the system on the implant side was implemented as an application specific integrated circuit (ASIC), fabricated in 0.6- [Formula: see text] high voltage CMOS technology. The theory of PPSK modulation, simulated and measured performance evaluation, and comparison with other state-of-the-art impedance modulation techniques is presented. The measured bit error rate around critical coupling at 1.35 Mbps is below 6 *10-8. PMID- 27654978 TI - Deep Neural Networks for Identifying Cough Sounds. AB - In this paper, we consider two different approaches of using deep neural networks for cough detection. The cough detection task is cast as a visual recognition problem and as a sequence-to-sequence labeling problem. A convolutional neural network and a recurrent neural network are implemented to address these problems, respectively. We evaluate the performance of the two networks and compare them to other conventional approaches for identifying cough sounds. In addition, we also explore the effect of the network size parameters and the impact of long-term signal dependencies in cough classifier performance. Experimental results show both network architectures outperform traditional methods. Between the two, our convolutional network yields a higher specificity 92.7% whereas the recurrent attains a higher sensitivity of 87.7%. PMID- 27654980 TI - Angiotensin Receptor Neprilysin Inhibitor Use Urgency: Festina Lente. PMID- 27654979 TI - Erratum to: Genotyping bacterial and fungal pathogens using sequence variation in the gene for the CCA-adding enzyme. PMID- 27654981 TI - Are carriers of CYP21A2 mutations less vulnerable to psychological stress? A population-based national cohort study. AB - BACKGROUND: Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic-pituitary-adrenal axis. We investigated vulnerability to psychological stress in obligate carriers. METHOD: The Swedish CAH Registry encompasses more than 600 patients. Parents, that is obligate carriers of the CYP21A2 mutation, were identified through the Multigeneration Register. The diagnosis of the child was used as the psychological stressor. Psychiatric diagnoses before and after the birth of a child with CAH were compared to those of controls derived from (i) the general population, (ii) parents of children with hypospadias and (iii) parents of children with diabetes mellitus type 1 (T1DM). RESULTS: Parents of children with CAH had less risk of being diagnosed with any psychiatric disorder (OR, 0.6), an affective disorder (OR, 0.5) or substance misuse (OR, 0.5) after the diagnosis of the child, compared to the general population. Their risk was also decreased compared to parents of a child with hypospadias (OR, 0.6, 0.4 and 0.2, respectively) and parents of a child with T1DM (OR 0.7, 0.6 and 0.2, respectively). The CYP21A2 carriers had a lower risk of developing mood and stress-related disorders after the diagnosis of the child. CONCLUSION: Obligate CYP21A2 carriers had a reduced risk of a psychiatric diagnosis and were less vulnerable to a psychologically stressful situation, at least with respect to receiving a psychiatric diagnosis. This indicates a better ability to cope with psychological stress among heterozygous carriers of severe CYP21A2 mutations, which may contribute to the apparent survival advantage. PMID- 27654982 TI - Robert M. Diener. PMID- 27654984 TI - 5th Iberian Primatological Congress. PMID- 27654983 TI - Placement of transnasal drainage catheter and covered esophageal stent for the treatment of perforated esophageal carcinoma with mediastinal abscess. AB - BACKGROUND AND OBJECTIVES: Perforated esophageal carcinoma with mediastinal abscess is a clinically life-threatening emergency. Herein, we summarize our experience with placement of transnasal drainage catheters and covered esophageal stents for the treatment of this condition. METHODS: We retrospectively assessed the medical records of 20 patients who were treated using our intervention protocol. Patients received local anesthesia and sedation prior to transnasal drainage catheter placement into the mediastinal abscess, which was followed by esophageal stent placement. Once the fluid was completely drained and the abscess was completely closed, the drainage catheter was removed. RESULTS: The placement of the drainage catheter and stent was successful in all patients. The drainage catheter was successfully removed from the mediastinum after 7-60 days in 14 patients. During the follow-up of 1-18 months, six patients died from hemorrhage, eight from cancer progression or pulmonary infection, one from atrial fibrillation, and one from asphyxia caused by tracheal compression. The remaining four patients can eat normally. CONCLUSIONS: Placement of transnasal drainage catheters and covered esophageal stents may be an appropriate palliative therapy for patients with perforated esophageal carcinoma with mediastinal abscess who are not candidates for surgery or have a high postoperative risk. J. Surg. Oncol. 2016;114:725-730. (c) 2016 Wiley Periodicals, Inc. PMID- 27654985 TI - Preclinical and Healthy Volunteer Studies of Potential Drug-Drug Interactions Between Tenapanor and Phosphate Binders. AB - Tenapanor (RDX5791, AZD1722), a first-in-class small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3. Tenapanor acts locally in the gut, where it reduces absorption of sodium and phosphate. It is being studied in patients with chronic kidney disease requiring dialysis, who are often administered phosphate binders such as sevelamer to help control hyperphosphatemia. We investigated whether coadministration of tenapanor with phosphate binders (sevelamer or calcium-based binders) impacts the pharmacodynamic effects of tenapanor. In vitro studies suggested a binding interaction between tenapanor and sevelamer, but this did not translate into altered pharmacodynamic effects in rats. An open-label, 2-way crossover study was then conducted in healthy volunteers (NCT02346890). This showed that 4 days' treatment with tenapanor hydrochloride (15 mg twice daily) with or without sevelamer carbonate (800 mg 3 times daily) resulted in comparable 24-hour stool and urinary sodium and phosphorus levels. Stool frequency, consistency, and weight were also comparable between the treatments. These results suggest that the binding between sevelamer and tenapanor observed in vitro does not translate into altered pharmacodynamic effects in humans. PMID- 27654987 TI - What is the contrast-filled structure seen during right ventriculography? PMID- 27654986 TI - A Contemporary Estimate of Total Mortality and Cardiovascular Disease Risk in Young Adults With Type 1 Diabetes: The Pittsburgh Epidemiology of Diabetes Complications Study. AB - OBJECTIVE: The degree to which mortality and cardiovascular disease (CVD) incidence remains elevated in young U.S. adults with type 1 diabetes (T1DM) is unclear. We determined contemporary rates for adults <45 years old with long standing, childhood-onset T1DM from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. RESEARCH DESIGN AND METHODS: Members of the EDC Study cohort <45 years old during the 1996-2012 follow-up period (n = 502) were studied. Mortality and CVD rates were calculated for those aged 30-39 and 40-44 years. Data from the background Allegheny County, Pennsylvania, population were used to calculate age- and sex-matched standardized mortality (SMR) and incidence rate ratios (IRR). RESULTS: In both age groups, the SMR for total mortality was ~5 (95% CIs: 30-39-year-olds, 2.8, 7.2; 40-44-year-olds, 3.4, 7.8). CVD mortality SMRs ranged from 19 (95% CI 11, 32) to 33 (95% CI 17, 59). Hospitalized CVD IRR was ~8 (95% CIs: 30-39-year-olds, 2.5, 18.9; 40-44-year-olds, 4.5, 12.8); revascularization procedures account for much of the increased risk. For all outcomes, the relative risk was larger in women. Participants aged 30-39 years had 6.3% (95% CI 3.8, 9.8) absolute 10-year CVD risk, approaching the American College of Cardiology/American Heart Association-recommended cut point of 7.5% for initiation of statin therapy in older adults. CONCLUSIONS: Total and CVD mortality and hospitalized CVD are all significantly increased in this contemporary U.S. cohort of young adults with long-standing T1DM. These findings support more aggressive risk factor management in T1DM, especially among women. PMID- 27654988 TI - Finger counting method is more accurate than age-based weight estimation formulae in estimating the weight of Hong Kong children presenting to the emergency department. AB - OBJECTIVE: The aim of the present study was to evaluate the finger counting method and compare its performance with four commonly used age-based weight estimation formulae in children aged 1-9 years presenting to the ED in Hong Kong. METHODS: A cross-sectional, observational study of children aged 1-9 years who presented to the ED of a tertiary referral hospital in Hong Kong over a 6 month period was conducted. Actual weight was compared with estimated weight using the finger counting method and four commonly used age-based weight estimation formulae. Bland-Altman analysis was performed to evaluate the degree of agreement in which the mean percentage difference (MPD) and 95% limits of agreement (LOA) were calculated. Root mean squared error (RMSE) and proportions of weight estimates within 10%, 15% and 20% of actual weight were determined. RESULTS: A total of 4178 children were included. The finger counting method was the most accurate method (MPD 0.1%; 95% LOA -34.0% to 34.2%). The original Advanced Paediatric Life Support (APLS) formula (MPD -7.0%; 95% LOA -38.4% to 24.3%) and the updated APLS formula (MPD -0.4%; 95% LOA -38.5% to 37.8%) underestimated weight whereas the Luscombe formula (MPD 7.2%; 95% LOA -31.8% to 46.2%) and the Best Guess formula (MPD 10.6%; 95% LOA -27.3% to 48.4%) overestimated weight. The finger counting method had smallest RMSE of 4.06 kg and estimated the largest proportion of children within 10%, 15% and 20% of actual weight. CONCLUSION: The finger counting method outperforms the commonly used age-based weight estimation formulae in children aged 1-9 years presenting to the ED in Hong Kong. PMID- 27654989 TI - Dependent stomach sign and dependent intestine sign of dorsal pancreatic agenesis. AB - The 'dependent stomach sign' and 'dependent intestine sign' have been typically described for agenesis of dorsal pancreas. It is useful to differentiate pancreatic agenesis from the fatty infiltration of pancreas which is seen in pancreatic atrophy and pancreatic lipomatosis. PMID- 27654991 TI - Diagnostic performance of stomach CT compared with endoscopic ultrasonography in diagnosing gastric subepithelial tumors. AB - PURPOSE: To evaluate the diagnostic ability of multi-detector computed tomography (MDCT) compared to endoscopic ultrasonography (EUS) as a standard reference, and investigate the factors influencing the detection of small gastric subepithelial tumors (SETs) (<5 cm) on MDCT with stomach protocol. METHODS: We retrospectively investigated 70 patients who were suspected with gastric SETs on esophagogastroduodenoscopy (EGD), and underwent both EUS and computed tomographic (CT) scanning. EUS was performed by two gastroenterologists, and location, size, echotexture, echogenicity, and layer of origin were described when gastric SETs were detected on EUS. MDCTs were reviewed based on consensus of two radiologists blinded to the EUS result. Size, location, enhancement pattern, and contour of the lesion detected on CT were described. We calculated the diagnostic ability of CT compared to EUS with respect to detection of gastric SETs, and investigated the factors influencing detection of SETs on CT. We also used receiver operating characteristic (ROC) curve to obtain optimal cut-off size for predicting CT visibility of small SETs. RESULTS: Of the 70 patients, who underwent both CT and EUS due to suspicious presence of SET on EGD, EUS detected 56 probable cases of SET and 14 cases of external compression. CT led to detection of 39 cases of SET out of the 56 cases. Sensitivity and specificity of CT was 69.6% and 100.0%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of CT were 100.0% and 45.2%, respectively. There was a significant difference in mean size of CT-detected lesions compared to CT-invisible lesions (14.36 mm vs. 8.52 mm, p < 0.001), but no significant differences in terms of layer of origin and location between these two groups (p > 0.5) were observed. The ROC analysis revealed that the optimal cut-off value, also referred to prediction of CT visibility, was 10 mm. Out of 70 cases, 26 cases (37.14%) were identified as external compression or insignificant lesions such as lipoma, hemangioma, lymphangioma, or gastritis cystica on CT, and do not require regular follow-up. CONCLUSIONS: Stomach CT shows good feasibility with respect to depiction of small SETs, especially in cases where size is larger than 10 mm. Henceforth, it is proposed that stomach CT would be a complimentary or problem-solving tool for SET in evaluating the presence of external compression and characterization of tumors. PMID- 27654990 TI - Diagnostic yield and clinical impact of microbiologic diagnosis from CT-guided drainage in patients previously treated with empiric antibiotics. AB - PURPOSE: The purpose of the study was to evaluate diagnostic yield and the added value of culture results on the clinical management of patients empirically treated with antibiotics prior to CT-guided drainage. METHODS: This retrospective, HIPAA-compliant, IRB-approved study reviewed records of 300 consecutive patients who underwent CT-guided aspiration or drainage for suspected infected fluid collection while on empiric antibiotics (11/2011 to 9/2013) at a single institution. Patient imaging and clinical characteristics were evaluated by an abdominal imaging fellow and culture results, and patient management were evaluated by an infectious diseases fellow. RESULTS: After exclusion of 14/300 (4.6%) patients who were not on empiric antibiotics and 8/300 (2.6%) patients in which no culture was acquired, 278 patients (average age 55 +/- 16 years; M:F ratio 54:46) constituted the final study cohort. Leukocytosis was present in 163/278 (59%), and fever in 65/278 (24%). The average collection size was 8.5 +/- 4.2 cm with gas present in 140/278 (50%) of collections; median amount drained was 35 mL, and visibly purulent material was obtained in 172/278 (63%). 236/278 (85%) received drains and the remainder were aspirated only. Average time between initiation of antibiotics and start of the drainage procedure was 4.1 +/- 6.4 days (median 1.7 days). Cultures were positive in 205/278 (74%) patients with a resulting change in management in 181/278 (65%) cases. The change in management included change of antibiotics in 71/278 (26%), narrowing the antibiotic regimen in 94/278 (34%), and cessation of antibiotics in 16/278 (6%). Multidrug-resistant bacteria were cultured in 53/278 (19%). Several factors were found to be statistically significant predictors of positive cultures: patient leukocytosis (sens 62%, spec 53%), gas in the collection on CT (sens 59%, spec 77%), purulent material aspiration (sens 76%, spec 76%), and presence of polymorphonuclear cells in the specimen. CONCLUSIONS: Despite predrainage antibiotic therapy, CT-guided drainage demonstrates a high yield of positive cultures and influences clinical management in the majority of patients. PMID- 27654992 TI - The Relationship between Power Generated by Thrust and Power to Overcome Drag in Elite Short Distance Swimmers. AB - At constant average speed (v), a balance between thrust force (Ft) and drag force (Fd) should occur: Ft-Fd = 0; hence the power generated by thrust forces (Pt = Ft.v) should be equal to the power needed to overcome drag forces at that speed (Pd = Fd.v); the aim of this study was to measure Pt (tethered swims), to estimate Pd in active conditions (at sprint speed) and to compare these values. 10 front crawl male elite swimmers (expertise: 93.1 +/- 2.4% of 50 m world record) participated to the study; their sprint speed was measured during a 30 m maximal trial. Ft was assessed during a 15 s tethered effort; passive towing measurement were performed to determine speed specific drag in passive conditions (kP = passive drag force/v2); drag force in active conditions (Fd = kA.v2) was calculated assuming that kA = 1.5.kP. Average sprint speed was 2.20 +/- 0.07 m.s 1; kA, at this speed, was 37.2 +/- 2.7 N.s2.m-2. No significant differences (paired t-test: p > 0.8) were observed between Pt (399 +/- 56 W) and Pd (400 +/- 57 W) and a strong correlation (R = 0.95, p < 0.001) was observed between these two parameters. The Bland-Altman plot indicated a good agreement and a small, acceptable, error (bias: -0.89 W, limits of agreement: -25.5 and 23.7 W). Power thrust experiments can thus be suggested as a valid tool for estimating a swimmer's power propulsion. PMID- 27654993 TI - Hard times and European youth. The effect of economic insecurity on human values, social attitudes and well-being. AB - While economic downturns have adverse effects on young people's life chances, empirical studies examining whether and to what extent human values, social attitudes and well-being indicators respond to sudden economic shocks are scarce. To assess the claim that human values are less affected by economic shocks than social attitudes and well-being, two distinct yet related studies based on the European Social Survey (ESS) are conducted. The first employs a fixed effects pseudo-panel analysis of the 2008-2014 ESS-waves to detect whether changes over time in the socio-demographic group's unemployment risk and national youth unemployment affect individual dispositions to varying degrees. The second study captures micro- and cross-national effects in the 2010 ESS cross-section. Unique for this set-up is that we can test whether the findings hold for over-time changes in youth unemployment within countries (pseudo-panel), as well as for cross-country differences in youth unemployment (multilevel). Both studies indicate that political trust, satisfaction with the economy and subjective well being are lowered by economic risk and hardship, while social trust and self rated health are less affected by changes in youth unemployment. Secondly, human values are immune to economic risk, underscoring that values transcend specific situations and are therefore resistant against sudden economic shocks. PMID- 27654994 TI - Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults. AB - BACKGROUND: Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. A new combination of dexketoprofen (a nonsteroidal anti-inflammatory drug) plus tramadol (an opioid) has been tested in acute postoperative pain conditions. It is not yet licensed for use. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single fixed-dose of oral dexketoprofen plus tramadol, compared with placebo, for moderate to severe postoperative pain in adults, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. A secondary objective was to compare the combination with the individual analgesics alone. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO, MEDLINE via Ovid, and Embase via Ovid from inception to 31 May 2016. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. SELECTION CRITERIA: Randomised, double-blind trials of oral dexketoprofen plus tramadol administered as a single oral dose, for the relief of acute postoperative pain in adults, and compared to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) for dexketoprofen plus tramadol, compared with placebo with 95% confidence intervals (CI). We collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.We also collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours for dexketoprofen alone and tramadol alone. MAIN RESULTS: We included three studies with 1853 participants who had undergone surgical removal of impacted wisdom teeth, hip replacement, or hysterectomy. The overall risk of bias across the three included studies was low, with unclear risk of bias in relation to the size of the three studies. Two studies did not report all our prespecified outcomes, which limited the analyses we could do.The proportion of participants achieving at least 50% pain relief over six hours with dexketoprofen 25 mg plus tramadol 75 mg was 66%, compared to 32% with placebo, giving an NNT of 3.0 (95% CI 2.5 to 3.7) (RR 2.1 (95% CI 1.7 to 2.4); 748 participants; 3 studies) (moderate quality evidence). The response rate with dexketoprofen 25 mg alone was 53% (RR 1.3 (95% CI 1.1 to 1.4); 744 participants; 3 studies) and with tramadol alone was 45% (RR 1.5 (95% CI 1.3 to 1.7); 741 participants; 3 studies) (moderate quality evidence). We downgraded the evidence because of some inconsistency in the results.The median time to use of rescue medication could not be estimated exactly, but was probably eight hours or more, indicating a long duration of effect (moderate quality evidence). We downgraded the evidence because it was not possible to estimate the effect exactly in the two multiple dose studies, resulting in imprecision. Fewer participants used rescue medication with higher doses of active treatment (summary statistic not calculated; 123 participants; 1 study) (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events.Adverse events and serious adverse events were not reported consistently for the single dose phase of the studies. In the single dose study, 11% of participants experienced adverse events with dexketoprofen 25 mg plus tramadol 75 mg, which were mostly mild or moderate nausea, vomiting, or dizziness, and typical with these medicines. Rates were lower with placebo and lower doses (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Information on multiple dosing over three and five days supported a low event rate with the combination. Overall, rates were generally low in all treatment arms, as they were for withdrawals for adverse events or other reasons. AUTHORS' CONCLUSIONS: A single oral dose of dexketoprofen 25 mg plus tramadol 75 mg provided good levels of pain relief with long duration of action to more people than placebo or the same dose of dexketoprofen or tramadol alone. The magnitude of the effect was similar to other good analgesics. Adverse event rates were low.There is modest uncertainty about the precision of the point estimate for efficacy, but the NNT of 3 is consistent with other analgesics considered effective and commonly used. PMID- 27654995 TI - Organoid Culture of Human Cancer Stem Cells. AB - Organoid culture is a three-dimensional culture method that enables ex vivo analysis of stem cell behavior and differentiation. This method is also applicable to the studies on stem cell characters of human cancer stem cells. The components of organoid culture include Matrigel(r) and a culture medium containing growth factor cocktails that mimic the microenvironments of organ stem cell niches. Here, we describe the basic methods for the organoid culture of dissociated or FACS-sorted human cancer stem cells. Then, we introduce a method to dissociate the organoids for serial passage and propagation. PMID- 27654996 TI - Venous thromboembolism following colorectal resection. AB - AIM: The study investigated the rate of significant venous thromboembolism (VTE) following colorectal resection during the index admission and over 1 year following discharge. It identifies risk factors associated with VTE and considers the length of VTE prophylaxis required. METHOD: All adult patients who underwent colorectal resections in England between April 2007 and March 2008 were identified using Hospital Episode Statistics data. They were studied during the index admission and followed for a year to identify any patients who were readmitted as an emergency with a diagnosis of deep venous thrombosis or pulmonary embolism. RESULTS: In all, 35 997 patients underwent colorectal resection during the period of study. The VTE rate was 2.3%. Two hundred and one (0.56%) patients developed VTE during the index admission and 571 (1.72%) were readmitted with VTE. Following discharge from the index admission, the risk of VTE in patients with cancer remained elevated for 6 months compared with 2 months in patients with benign disease. Age, postoperative stay, cancer, emergency admission and emergency surgery for patients with inflammatory bowel disease (IBD) were all independent risk factors associated with an increased risk of VTE. Patients with ischaemic heart disease and those having elective minimal access surgery appear to have lower levels of VTE. CONCLUSION: This study adds to the benefits of minimal access surgery and demonstrates an additional risk to patients undergoing emergency surgery for IBD. The majority of VTE cases occur following discharge from the index admission. Therefore, surgery for cancer, emergency surgery for IBD and those with an extended hospital stay may benefit from extended VTE prophylaxis. This study demonstrates that a stratified approach may be required to reduce the incidence of VTE. PMID- 27654997 TI - Homogenous Boron-doping in Self-sensitized Carbon Nitride for Enhanced Visible light Photocatalytic Activity. AB - We report a solvothermal approach for the preparation of homogeneously B-doped self-sensitized carbon nitride (B-SSCN) composed of a core of B-doped carbon nitride microspheres and a covalently linked shell of s-triazine oligomers. Compared to the undoped structure, the obtained B-SSCN photocatalyst exhibits an enhanced visible-light activity, excellent stability for photocatalytic hydrogen generation due to a reduced band-gap, enhanced charge-separation efficiency, and better surface reactivity of B-SSCN. This work provides a new strategy to uniformly insert heteroatoms into the polymeric carbon nitride framework for the development of metal-free photocatalysts towards efficient production of solar fuels. PMID- 27654998 TI - Effect of corneal cross-linking on contact lens tolerance in keratoconus. AB - BACKGROUND: The aim was to investigate changes in corneal sensation and rigid gas permeable (RGP) contact lens tolerance after corneal cross-linking (CXL) on patients with keratoconus. METHODS: Thirty eyes of 30 patients, who were RGP lens intolerant, were treated with CXL. The main outcome measures were corneal sensation evaluation by Cochet-Bonnet esthesiometry, sub-basal nerve fibre assessment by corneal in vivo confocal microscopy and RGP contact lens tolerance evaluation with the Likert scale and wearing time. All eyes were evaluated preoperatively and post-operatively at one, three and six months after CXL procedure. RESULTS: The mean age was 25.3 +/- 6.2 years. Preoperatively, the maximum keratometry (Kmax) in study eyes was 56.89 +/- 4.60 D. Six months after CXL, it reduced to 56.03 +/- 4.85 D (p = 0.01). Preoperative mean corneal sensation was 0.44 +/- 0.05 g/mm2 , (range: 0.40 to 0.55); it was significantly decreased at the first month and increased to preoperative values after six months. The sub-basal nerve plexus could not be visualised in 90 per cent of the patients by confocal microscopy at one month post-operatively. Gradual restoration of corneal innervation with almost similar preoperative levels at post-operative month six was noted. There were significant differences in Likert scores between preoperative and third and sixth months after CXL. Likert scale scores correlated significantly with corneal sensitivity. CONCLUSION: It can be concluded that increased RGP contact lens tolerance after CXL may be associated with the potential role of decreased corneal sensitivity and corneal flattening after CXL. PMID- 27655000 TI - Becker's nevus syndrome: a report of a rare disease with unusual associations. PMID- 27655001 TI - Measuring Information Security Performance with 10 by 10 Model for Holistic State Evaluation. AB - Organizations should measure their information security performance if they wish to take the right decisions and develop it in line with their security needs. Since the measurement of information security is generally underdeveloped in practice and many organizations find the existing recommendations too complex, the paper presents a solution in the form of a 10 by 10 information security performance measurement model. The model-ISP 10*10M is composed of ten critical success factors, 100 key performance indicators and 6 performance levels. Its content was devised on the basis of findings presented in the current research studies and standards, while its structure results from an empirical research conducted among information security professionals from Slovenia. Results of the study show that a high level of information security performance is mostly dependent on measures aimed at managing information risks, employees and information sources, while formal and environmental factors have a lesser impact. Experts believe that information security should evolve systematically, where it's recommended that beginning steps include technical, logical and physical security controls, while advanced activities should relate predominantly strategic management activities. By applying the proposed model, organizations are able to determine the actual level of information security performance based on the weighted indexing technique. In this manner they identify the measures they ought to develop in order to improve the current situation. The ISP 10*10M is a useful tool for conducting internal system evaluations and decision-making. It may also be applied to a larger sample of organizations in order to determine the general state-of-play for research purposes. PMID- 27654999 TI - Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms. AB - BACKGROUND: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. RESULTS: Here, we report on the large-scale identification of 6366 age-related variably methylated positions (aVMPs) identified in 3295 whole blood DNA methylation profiles, 2044 of which have a matching RNA-seq gene expression profile. aVMPs are enriched at polycomb repressed regions and, accordingly, methylation at those positions is associated with the expression of genes encoding components of polycomb repressive complex 2 (PRC2) in trans. Further analysis revealed trans associations for 1816 aVMPs with an additional 854 genes. These trans-associated aVMPs are characterized by either an age-related gain of methylation at CpG islands marked by PRC2 or a loss of methylation at enhancers. This distinct pattern extends to other tissues and multiple cancer types. Finally, genes associated with aVMPs in trans whose expression is variably upregulated with age (733 genes) play a key role in DNA repair and apoptosis, whereas downregulated aVMP-associated genes (121 genes) are mapped to defined pathways in cellular metabolism. CONCLUSIONS: Our results link age-related changes in DNA methylation to fundamental mechanisms that are thought to drive human ageing. PMID- 27655003 TI - Materials and Methods. AB - Mice obtained for this study were products of pudgy breeding pairs from Jackson Laboratories, Bar Harbor, Maine. For the affected pudgy mice, heterozygous unaffected littermates served as controls. An affected pudgy mouse (pu/pu) can be identified at birth since it is approximately three-quarters the length of its non-affected littermates (pu/+) and has a markedly shortened, twisted tail. The mice were sacrificed by intraperitoneal injections of sodium pentobarbital. Vertebral and rib assessments were performed in 68 mice, 37 affected (pu/pu) and 31 non-affected (pu/+) age-matched siblings from the late embryo to 3 months of age. There were eight sets of births (litters) in which two or more of the sibling littermates were affected, allowing for a comparison of rib and vertebral anomalies in pudgy mice from the same mother and same pregnancy as well as with all other pudgy mice. PMID- 27655004 TI - Results. AB - Table 3.1 outlines ages of pudgy and non-affected mice, sibling groups with two or more littermates affected, and types of structural studies performed in each mouse. Table 3.2 outlines the age distribution of the studies. PMID- 27655005 TI - Discussion. AB - Each of the radiographic, histologic, whole mount, and three-dimensional computerized reconstruction techniques throws specific light on the vertebral, intervertebral disc, and rib abnormalities in the development of the pudgy mouse. The end result demonstrates a failure of both normal formation and normal segmentation in the pudgy mouse recognized now as a recessive genetic disorder in which mutations in the Delta-like 3 gene (Dll3) have been defined [2]. The variable appearance of the vertebral and rib abnormalities from mouse to mouse, including in particular the variable appearance in affected littermates, indicates that the gene abnormality alone does not account solely for the deformities seen. Once the gene abnormality is expressed early in embryogenesis, secondary effects, presumably by mechanisms of epigenetics, appear to play a significant role in outlining the abnormal pattern. The pudgy mouse and other genetically triggered axial developmental abnormalities represent excellent models to help unravel pathogenetic mechanisms whereby gene abnormalities are translated into three-dimensional structural abnormalities. PMID- 27655002 TI - Disordered vertebral and rib morphology in pudgy mice. Structural relationships to human scoliosis. AB - Normal and abnormal vertebral development have been studied over the past 200 years at increasing levels of resolution as techniques for biological investigation have improved. Disordered development of the axial skeleton from the early embryonic period on leads to structurally malformed vertebrae and intervertebral discs and ribs causing the severe deformities of scoliosis, kyphosis, and kyphoscoliosis. Developmental malformation of the axial skeleton therefore has led to considerable biological and clinical interest. This work will detail our studies on the structural deformities of the vertebral column and adjacent ribs in the pudgy mouse [1] caused by mutations in the delta-like 3 (Dll3) gene of the Notch family [2]. While gene abnormalities in the pudgy mouse have been outlined, there has been no in-depth assessment of the histopathology of the pudgy vertebral and rib abnormalities that this study will provide. In addition, although congenital scoliosis has been recognized as a clinical problem since the mid-nineteenth century (1800s) [3] and accurately defined by radiography since the early twentieth century (1900s) [4-6], there have been few detailed histopathologic studies of human cases. We will also relate our histopathologic findings in the pudgy mouse to the histopathology of human vertebral and rib malformations in clinical cases of congenital scoliosis, one of which we defined in detail previously [7]. PMID- 27655006 TI - Conclusions. AB - The abnormal findings in the pudgy mouse are remarkably similar to those in the severe case of human congenital scoliosis such as seen in the spondylocostal dysplasias. The pudgy mouse is an excellent model to study: (i) how gene mutations translate into three-dimensional structural abnormalities and (ii) which other factors contribute to the final deformities. PMID- 27655007 TI - The "Universal" in UHC and Ghana's National Health Insurance Scheme: policy and implementation challenges and dilemmas of a lower middle income country. AB - BACKGROUND: Despite universal population coverage and equity being a stated policy goal of its NHIS, over a decade since passage of the first law in 2003, Ghana continues to struggle with how to attain it. The predominantly (about 70 %) tax funded NHIS currently has active enrolment hovering around 40 % of the population. This study explored in-depth enablers and barriers to enrolment in the NHIS to provide lessons and insights for Ghana and other low and middle income countries (LMIC) into attaining the goal of universality in Universal Health Coverage (UHC). METHODS: We conducted a cross sectional mixed methods study of an urban and a rural district in one region of Southern Ghana. Data came from document review, analysis of routine data on enrolment, key informant in depth interviews with local government, regional and district insurance scheme and provider staff and community member in-depth interviews and focus group discussions. RESULTS: Population coverage in the NHIS in the study districts was not growing towards near universal because of failure of many of those who had ever enrolled to regularly renew annually as required by the NHIS policy. Factors facilitating and enabling enrolment were driven by the design details of the scheme that emanate from national level policy and program formulation, frontline purchaser and provider staff implementation arrangements and contextual factors. The factors inter-related and worked together to affect client experience of the scheme, which were not always the same as the declared policy intent. This then also affected the decision to enrol and stay enrolled. CONCLUSIONS: UHC policy and program design needs to be such that enrolment is effectively compulsory in practice. It also requires careful attention and responsiveness to actual and potential subscriber, purchaser and provider (stakeholder) incentives and related behaviour generated at implementation levels. PMID- 27655009 TI - Is Genome Complexity a Consequence of Inefficient Selection? Evidence from Intron Creation in Nonrecombining Regions. AB - Genomes show remarkable variation in architecture and complexity across organisms, with large differences in genome size and in numbers of genes, gene duplicates, introns and transposable elements. These differences have important implications for transcriptome and regulatory complexity and ultimately for organismal complexity. Numbers of spliceosomal introns show particularly striking differences, ranging across organisms from zero to hundreds of thousands of introns per genome. The causes of these differences remain poorly understood. According to one influential perspective, differences across species reflect the differential ability of selection in different populations to eliminate allegedly deleterious intron-containing alleles. Direct tests of this theory have been elusive. Here, I study evolution of intron-exon structures in genomic regions of recombination suppression (RRSs), which experience drastically reduced selective efficiency due to hitchhiking and background selection. I studied intron creation in eight independently evolved RRSs, spanning substantial diversity phylogenetically (plants, animals, fungi and brown algae) and biologically (sex chromosomes, mating type chromosomes, genomic regions flanking self incompatibility loci, and the Drosophila "dot" chromosome). To identify newly created introns in RRSs, I compared intron positions in RRS genes with those in homologous genes. I found very few intron gains: no intron gains were observed in 7/8 studied data sets, and only three intron gains were observed overall (on the Drosophila dot chromosome). These results suggest that efficiency of selection may not be a major cause of differences in intron-exon structures across organisms. Instead, rates of spontaneous intron-creating and intron-deleting mutations may play the central role in shaping intron-exon structures. PMID- 27655010 TI - Doctors are working five unpaid extra weeks a year, claim leaders. PMID- 27655008 TI - Small-World Brain Networks Revisited. AB - It is nearly 20 years since the concept of a small-world network was first quantitatively defined, by a combination of high clustering and short path length; and about 10 years since this metric of complex network topology began to be widely applied to analysis of neuroimaging and other neuroscience data as part of the rapid growth of the new field of connectomics. Here, we review briefly the foundational concepts of graph theoretical estimation and generation of small world networks. We take stock of some of the key developments in the field in the past decade and we consider in some detail the implications of recent studies using high-resolution tract-tracing methods to map the anatomical networks of the macaque and the mouse. In doing so, we draw attention to the important methodological distinction between topological analysis of binary or unweighted graphs, which have provided a popular but simple approach to brain network analysis in the past, and the topology of weighted graphs, which retain more biologically relevant information and are more appropriate to the increasingly sophisticated data on brain connectivity emerging from contemporary tract-tracing and other imaging studies. We conclude by highlighting some possible future trends in the further development of weighted small-worldness as part of a deeper and broader understanding of the topology and the functional value of the strong and weak links between areas of mammalian cortex. PMID- 27655011 TI - Oxidative Cleavage of C=S and P=S Bonds at an AlI Center: Preparation of Terminally Bound Aluminum Sulfides. AB - The treatment of cyclic thioureas with the aluminum(I) compound NacNacAl (1; NacNac=[ArNC(Me)CHC(Me)NAr]- , Ar=2,6-Pri2 C6 H3 ) resulted in oxidative cleavage of the C=S bond and the formation of 3 and 5, the first monomeric aluminum complexes with an Al=S double bond stabilized by N-heterocyclic carbenes. Compound 1 also reacted with triphenylphosphine sulfide in a similar manner, which resulted in cleavage of the P=S bond and production of the adduct [NacNacAl=S(S=PPh3 )] (8). The Al=S double bond in 3 can react with phenyl isothiocyanate to furnish the cycloaddition product 9 and zwitterion 10 as a result of coupling between the liberated carbene and PhN=C=S. All novel complexes were characterized by multinuclear NMR spectroscopy, and the structures of 5, 9, and 10 were confirmed by X-ray diffraction analysis. The nature of the Al=S bond in 5 was also probed by DFT calculations. PMID- 27655013 TI - Human rights and proactive displacement: determining the appropriate balance between the duty to protect and the right to remain. AB - The proactive displacement by public authorities of populations from areas perceived to be exposed to a high risk of disaster presents complex human rights challenges. Provided that no ulterior motive is at play, the use of compulsory evacuations and relocations as policy responses to such risk is mandated by the duty to protect the right to life. However, proactive displacement in the interest of saving lives can be problematic as such measures can lead to the limitation of other human rights, resulting in an intricate assessment of whether compulsory evacuation or permanent relocation is proportional in any given circumstance. Such an analysis demands critical attention by public authorities to the perception of the disaster risk in question and problematises claims to objectivity of official risk assessments. Furthermore, it poses the question as to whether measures designed to address the disaster risk in question that are less intrusive than relocation may be available to public authorities. PMID- 27655012 TI - The effect of sodium nitroprusside on psychotic symptoms and spatial working memory in patients with schizophrenia: a randomized, double-blind, placebo controlled trial. AB - BACKGROUND: Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia. METHOD: This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18-60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 MUg/kg per min for 4 h) or placebo and were re assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later. RESULTS: SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo. CONCLUSIONS: Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms. PMID- 27655014 TI - The role of physical activity in early adulthood and middle-age on bone health after menopause in epidemiological population from Silesia Osteo Active Study. AB - BACKGROUND: Osteoporosis is a growing problem in women after menopause. Among factors protecting from this disease is a physical activity (PA). AIM: The objective of the study was to evaluate the influence of PA in early adulthood and at middle-age on bone health after menopause. MATERIAL AND METHODS: The study group consisted of 362 randomly recruited postmenopausal women after menopause. Mean age was 65.2+/-6.9 years. Medical history was collected from all participants, and they completed questionnaires assessing PA in early adulthood and at middle-age. Physical capacity was estimated using the Duke scale. Bone status was measured with use of densitometry (DXA) for lumbar spine and hip and calcaneus quantitative ultrasound (QUS) measurements. RESULTS: Physical activity and healthy lifestyle activity in early adulthood did not correlate with bone health, but current PA did (for QUS parameters r=.11; P<.05). Physical capacity correlated with all QUS parameters (r=.2 to .22; P<.05) and femoral neck (FN) BMD and T-score (for both r=.16; P<.05). Current PA frequency at the level of several times a week has the highest positive impact on FN DXA results (P=.01). Bone mass in DXA and QUS variables is related to the type of exercises (P<.05). CONCLUSION: Physical activity, especially several times a week, at middle-age is a major factor influencing bone health in women after menopause. Further studies concerning the type of exercises are needed. PMID- 27655015 TI - 3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep. AB - Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and beta-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p < 0.05). In conclusion, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017. PMID- 27655016 TI - Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission rather than a virological synapse. AB - Epstein-Barr virus (EBV) establishes a lifelong latent infection in B lymphocytes and often is found in epithelial cells. Several lines of evidence indicate that viral transmission mediated by cell-to-cell contact is the dominant mode of infection by EBV for epithelial cells. However, its detailed molecular mechanism has not been fully elucidated. We investigated the role of host membrane trafficking machinery in this process. We have found that adhesion molecules critical for this process are expressed in EBV-positive and -negative Burkitt's lymphoma (BL) cells and multiple epithelial cell lines. Treatment with blocking antibodies against beta1 and beta2 integrin families and their ligands suppressed EBV transmission in a dose-dependent manner. We also confirmed that adhesion molecules are upregulated in co-cultured BL cells. Immunofluorescence staining revealed that the intracellular adhesion molecule 1 (ICAM-1) distributed to the cell surface and partially co-localized with recycling endosomes in co-cultured BL cells. Moreover, cell-to-cell EBV transmission was inhibited upon blocking endocytic recycling by expression of a dominant-negative form of a small GTPase Rab11 or by knockdown of Rab11, supporting the notion that the endocytic pathway dependent trafficking of ICAM-1 to the cell surface of BL cells contributes to viral transmission by stabilizing cell-to-cell contact between the donor cells and recipient cells. Finally, we demonstrated that co-cultivation upregulated clathrin-mediated endocytosis in the recipient cells, allowing EBV to be internalized. Taken together, our findings demonstrate that EBV exploits host endocytic machinery in both donor and recipient cells, a process which is facilitated by cell-to-cell contact, thereby promoting successful viral transmission. PMID- 27655017 TI - Paediatric clinical exposure for medical students: Are they seeing enough? AB - AIM: To determine whether students are exposed to the 25 clinical presentations included in a comprehensive paediatric curriculum based on presenting features, as well as to evaluate for any variation in case exposure between the different locations and seasons of the student attachments. METHODS: Students in the final 2 years of a 6-year medical degree completed logbooks during their 8-week paediatric attachment, recording which of 25 listed clinical presentations they had seen. Data were then collected regarding the period and location of the clinical placement, and which presentations had been seen by each student. Analysis was performed to detect differences in student case exposure depending on location and season of attachment, as well as the frequency with which each presentation was seen. RESULTS: Three hundred and sixty-one student logbooks were included for analysis. Only one student had seen all 25 presentations; the median (range; interquartile range) number of cases seen was 14 (4-25; 11-17). There was no significant difference in the number of cases seen relating to location (rural, metropolitan or tertiary children's hospital) or season of the paediatric attachment. Only three presentations (infant/child with fever, breathing difficulties and vomiting/diarrhoea) had been seen by more than 90% of students; nine presentations had been seen by less than 50% of students. CONCLUSIONS: Students rarely gain exposure to all clinical presentations suggested in a comprehensive paediatric curriculum based on presenting features during an 8-week clinical attachment. Students have a similar experience regardless of the hospital or season of attachment. PMID- 27655018 TI - The role of executive control in the activation of manual affordances. AB - We investigated the role of executive control processes in the activation of manual affordances in two experiments combining stimulus-response compatibility (SRC) and dual-task paradigms. We registered an inverse SRC effect in the presence of a parallel backward-counting task in Experiment 1, and a cancellation of the SRC effect in Experiment 2 when a parallel Stroop-like task was used. We interpret our data as supporting a self-inhibition account of the affordance activation control. Accordingly, the role of executive processes is to prevent self-inhibition in supraliminal conditions: when cognitive resources are depleted by a parallel task, the self-inhibition mechanism becomes active and irrelevantly potentiated affordances are inhibited, leading to the emergence of an inverse SRC effect. In addition, the difference between data patterns observed in the two experiments suggests that the exact roles of the executive processes involved during the activation of affordances may differ. The results suggest a mechanism for action-related activation monitoring based on a flexible control over automatically potentiated actions. The paper discusses the proposed mechanism in detail and outlines further research directions. PMID- 27655019 TI - Clinical implications of microbial biofilms in chronic rhinosinusitis and orbital cellulitis. AB - BACKGROUND: Discovery of sessile mode of microbial existence (Biofilm state) focussed much interest, during the recent years, on the study of biofilms in many recurring and chronic infections. However, the exact role of microbial biofilms in chronic rhinosinusitis and orbital cellulitis were not elucidated earlier. The purpose of the present study was to look for the adherent property and biofilm producing ability of the clinical isolates in chronic rhinosinusitis and orbital cellulitis, and to look for the effects of antimicrobial agents on these biofilms by colorimetric assay and ultrastructural analysis. METHODS: Organisms were isolated and identified from various clinical samples in patients with chronic sinusitis and orbital cellulitis. Antimicrobial sensitivity testing was carried out by the standard protocol. Biofilms were developed; quantified and antimicrobial drug perfusion through the biofilm model was evaluated by the earlier devised procedure. Electronmicroscopic study of the biofilm was performed by the recommended technique. RESULTS: Of the total of 70 clinical samples processed, 48 i.e. 68.5 % grew bacteria and 13 i.e.(18.6 %) fungi. Staphylococcus aureus (20), S epidermidis (16) and Pseudomonas aeruginosa (6) accounted for the majority of the bacterial isolates. Aspergillus flavus (8), however was the commonest amongst the fungi. A total of 40 bacteria and 8 fungi could be tested for biofilm production. Eighteen (45 %) of the 40 bacterial isolates and 4(50 %) out of the 8 A flavus isolates were found to be biofilm producers. In vitro adherence testing revealed that majority i.e. 16 (88.8 %) of the 18 biofilm positive bacteria were adherent to artificial surfaces. Antimicrobial drug perfusion through the biofilm model was poor. Antimicrobial treatment was totally ineffective against strong biofilm producers, whose electron microscopic picture was quite similar to that observed for biofilm producers without any antimicrobial pre-treatment. CONCLUSIONS: Filamentous fungi, like bacteria were capable of forming biofilms, which could be one of the important virulence factors in determining the pathogenic potential of these organisms in causing chronic rhinosinusitis and orbital cellulitis. PMID- 27655020 TI - Biological function and mechanism of MALAT-1 in renal cell carcinoma proliferation and apoptosis: role of the MALAT-1-Livin protein interaction. AB - Long noncoding RNAs (lncRNAs) have been shown to play a critical role in cancer development and progression. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) is a kidney cancer-associated onco-lncRNA involved in the progression of renal cell carcinoma (RCC). However, the pathological role of lncRNA MALAT-1 in RCC proliferation and metastasis remains poorly understood. This study was designed to investigate the biological role and mechanism of MALAT 1 in RCC proliferation and metastasis. The experiments were performed in human tissues, renal carcinoma cell lines, and nude mice. The expression of lncRNA MALAT-1, Livin mRNA, and the Livin protein was determined by quantitative real time PCR (qRT-PCR) or a Western blot. The interaction between MALAT-1 and Livin was evaluated by RNA pull-down and RNA binding protein immunoprecipitation (RIP). Cell viability and apoptosis in RCC cell lines were detected using CCK-8 and TUNEL assays. LncRNA MALAT-1 and the Livin protein were highly expressed in RCC tissues, as well as in RCC 786-O and Caki-1 cell lines. MALAT-1 interference contributed to an increase in cell apoptosis and a reduction in the cell viability of 786-O and Caki-1 cells. The increase in apoptosis by si-MALAT-1 was reversed by overexpression of Livin. The RIP results showed that MALAT-1 promoted the expression of the Livin protein in 786-O and Caki-1 cells by enhancing the stability of the protein. Furthermore, the volume of si-MALAT-1-786-O cell xenograft was significantly suppressed. These data indicate that lncRNA MALAT-1 mediated promotion of RCC proliferation and metastasis may be due to the upregulation of the expression of Livin. PMID- 27655021 TI - The vital prognosis of elderly adults living in a group home in their mid eighties. AB - The purpose of the present study is to evaluate the vital prognoses of elderly people in their mid-eighties living in a group home (GH) compared to age- and sex matched outpatient clinic (OPC) in an observational study conducted over 6 years. We investigated the association between mortality and general, cardiac, and nutritional parameters, including eicosapentaenoic acid (EPA) in 54 GH residents (83 +/- 8 years old) and 57 OPC attendees (83 +/- 5 years old). Kaplan-Meier curves and Cox proportional hazard ratio analyses were used to assess the association between EPA drug administration and mortality in the GH residents and OPC attendees, respectively. The 54 GH residents had higher mortality and poorer nutritional states, as indicated by lower EPA/arachidonic acid values (median 0.20 vs 0.55, p < 0.001), and BMI under the condition without EPA drug administration (1800 mg daily) than did the OPC group. The significant factors that differed between survivors and deceased in the GH residents and OPC attendees were nutritional and cardiac factors. Cox proportional hazard ratio analysis confirmed that a possible determinant of the prognosis was a lower incidence of EPA drug administration and lower hemoglobin in GH. Kaplan-Meier curves and Cox proportional hazard ratio analyses revealed that EPA drug administration significantly reduced the relative mortality by 82 % in the GH residents (p < 0.001) but not in the OPC attendees. The vital prognosis in individuals from GHs was potentially improved by EPA drug administration, which was not the case in the OPC group; however, further prospective studies are needed. PMID- 27655022 TI - Desensitization of menthol-activated cold receptors in lower extremities during local cooling in young women with a cold constitution. AB - To test the hypothesis that topical menthol-induced reactivity of cold sensation and cutaneous vasoconstriction to local cooling is augmented in individuals with a cold constitution, we examined thermal sensation and cutaneous vasoconstrictor responses at menthol-treated and untreated sites in the legs during local skin cooling in young women complaining of chilliness (C group) and young women with no complaint as a normal control group (N group). During local skin cooling, the sensitivity to cold sensation was greater in the C group than in the N group. The application of menthol enhanced the cold sensation at a low temperature in the N group, but not in the C group. Cutaneous vasoconstrictor responses to local skin cooling were not altered by menthol treatment in either of the two groups. These findings suggest the desensitization of menthol-activated cold receptors in the legs of C group subjects, and a minor role of cold receptor activity in cutaneous vasoconstrictor response to local cooling. PMID- 27655023 TI - The Role of Visual and Haptic Feedback During Dynamically Coupled Bimanual Manipulation. AB - The mechanisms that underlie the control of bimanual actions in which the two hands act separately to manipulate different objects (uncoupled independent control) has been well studied. In contrast, much less is known about how the central nervous system controls bimanual actions that require the two hands act cooperatively to manipulate a single object (dynamically coupled control). Furthermore, there is scant research into the manual lateralization and role assignment in the processing of visual and haptic feedback during dynamically coupled bimanual tasks. In this experiment, we examined the role of the dominant and non-dominant hands during a dynamically coupled bimanual task in which visual and haptic feedback regarding object penetration were manipulated. Twelve subjects performed a bimanual grasp and reach task towards different target locations in the workspace by using two identical wrist robotic devices. Results showed haptic feedback is necessary for task completion, and that hand specialization plays a fundamental role in spatial and temporal coordination between the two limbs. PMID- 27655024 TI - Occupancy of the Invasive Feral Cat Varies with Habitat Complexity. AB - The domestic cat (Felis catus) is an invasive exotic in many locations around the world and is thought to be a key factor driving recent mammal declines across northern Australia. Many mammal species native to this region now persist only in areas with high topographic complexity, provided by features such as gorges or escarpments. Do mammals persist in these habitats because cats occupy them less, or despite high cat occupancy? We show that occupancy of feral cats was lower in mammal-rich habitats of high topographic complexity. These results support the idea that predation pressure by feral cats is a factor contributing to the collapse of mammal communities across northern Australia. Managing impacts of feral cats is a global conservation challenge. Conservation actions such as choosing sites for small mammal reintroductions may be more successful if variation in cat occupancy with landscape features is taken into account. PMID- 27655026 TI - Use of Perfluorodecalin for Bronchoalveolar Lavage in Case of Severe Pulmonary Hemorrhage and Extracorporeal Membrane Oxygenation: A Case Report and Review of the Literature. AB - We present a patient on venovenous extracorporeal membrane oxygenation for respiratory failure, secondary to complete airway obstruction from pulmonary hemorrhage after open pulmonary embolectomy. Obstruction was refractory to conventional therapy, including mechanical debridement and saline lavage. By using perfluorodecalin, we were able to transiently clear the airways of thrombus and reopen distal airways and alveoli more completely than with conventional therapies. The use of perfluorodecalin (versus radiopaque perflubron) enabled us to visualize this reopening on chest X-ray. PMID- 27655025 TI - An exploratory look at NETosis in atherosclerosis. AB - Current evidence suggests the likelihood of a link between venous thromboembolism (VTE) and atherosclerosis, although they have been traditionally considered as different pathological entities. The contribution of neutrophils to human atherogenesis has been underestimated, if compared to their contribution established in VTE. This is due to the major importance attributed to macrophages in plaque destabilization. Nevertheless, the role of neutrophils in atherogenesis deserves increasing attention. In particular, neutrophil extracellular traps (NETs) are net-like chromatin fibres that are released from dying neutrophils. The death of neutrophils with NETs formation is called NETosis. During activation, neutrophils produce reactive oxygen species (ROS), through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The main function of NETs is trapping and killing pathogens. Nevertheless, NETs formation has been observed in various chronic inflammatory diseases, autoimmune diseases, vasculitis, lung diseases, cancer and VTE. Recent studies suggest that NETs formation might contribute also to atherosclerosis progression. New data report the presence of NETs in the luminal portion of human atherosclerotic vessels and coronary specimens obtained from patients after acute myocardial infarction. Programmed death mechanisms in atherosclerosis such as apoptosis, efferocytosis and also NETosis, share common features and triggers. If defective, they can lead the cells to a switch from programmed death to necrosis, resulting in the release of pro-atherogenic factors, accumulation of cell debris and progression of the disease. This review provides evidence on the emerging role of neutrophils focusing on NETosis and oxidative stress burden in orchestrating common mechanisms in atherosclerosis and thrombosis. PMID- 27655028 TI - Correction: Molecular Paleoclimate Reconstructions over the Last 9 ka from a Peat Sequence in South China. AB - [This corrects the article DOI: 10.1371/journal.pone.0160934.]. PMID- 27655027 TI - [Posttraumatic deformities of the knee joint : Intra-articular osteotomy after malreduction of tibial head fractures]. AB - Malreduction of tibial head fractures often leads to malalignment of the lower extremity, pain, limited range of motion and instability. The extent of the complaints and the degree of deformity requires an exact analysis and a standardized approach. True ligamentous instability should be distinguished from pseudoinstability of the joint. Also extra- and intra-articular deformities have to be differentiated. In intra-articular deformities the extent of articular surface displacement, defects and clefts must be accurately evaluated. A specific surgical approach is necessary, which allows adequate visualization, correct osteotomy and refixation of the fractured area of the tibial head. In the long term course good clinical results are described for intra-articular osteotomies. If the joint is damaged to such an extent that it cannot be reconstructed or in cases of advanced posttraumatic osteoarthritis, total knee arthroplasty may be necessary; however, whenever possible and reasonable, anatomical reconstruction and preservation of the joint should be attempted. PMID- 27655029 TI - Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients. AB - BACKGROUND: Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta-lactam antibiotics. METHODS: We studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2-3 days when feasible. Glomerular filtration rate (GFR) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C (eGFR) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/l for piperacillin and meropenem respectively. RESULTS: We analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin-tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7-52.9) and 8.6 (2.7-30.3); and for meropenem, 7.5 (4.7-10.2) and 2.4 (1.0-3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR. The correlation with terminal concentration half-life was similar for eGFR and CrCl. CONCLUSIONS: With standard doses of meropenem and piperacillin-tazobactam, plasma concentrations in ICU patients vary > 10-fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function. PMID- 27655030 TI - Suppressor of Cytokine Signalling 2 (SOCS2) Regulates Numbers of Mature Newborn Adult Hippocampal Neurons and Their Dendritic Spine Maturation. AB - Overexpression of suppressor of cytokine signalling 2 (SOCS2) has been shown to promote hippocampal neurogenesis in vivo and promote neurite outgrowth of neurons in vitro. In the adult mouse brain, SOCS2 is most highly expressed in the hippocampal CA3 region and at lower levels in the dentate gyrus, an expression pattern that suggests a role in adult neurogenesis. Herein we examine generation of neuroblasts and their maturation into more mature neurons in SOCS2 null (SOCS2KO) mice. EdU was administered for 7 days to label proliferative neural precursor cells. The number of EdU-labelled doublecortin+ neuroblasts and NeuN+ mature neurons they generated was examined at day 8 and day 35, respectively. While no effect of SOCS2 deletion was observed in neuroblast generation, it reduced the numbers of EdU-labelled mature newborn neurons at 35 days. As SOCS2 regulates neurite outgrowth and dentate granule neurons project to the CA3 region, alterations in dendritic arborisation or spine formation may have correlated with the decreased numbers of EdU-labelled newborn neurons. SOCS2KO mice were crossed with Nes-CreERT2/mTmG mice, in which membrane eGFP is inducibly expressed in neural precursor cells and their progeny, and the dendrite and dendritic spine morphology of newborn neurons were examined at 35 days. SOCS2 deletion had no effect on total dendrite length, number of dendritic segments, number of branch points or total dendritic spine density but increased the number of mature "mushroom" spines. Our results suggest that endogenous SOCS2 regulates numbers of EdU-labelled mature newborn adult hippocampal neurons, possibly by mediating their survival and that this may be via a mechanism regulating dendritic spine maturation. PMID- 27655032 TI - Knowledge and awareness of genital involvement and reproductive health consequences of urogenital schistosomiasis in endemic communities in Ghana: a cross-sectional study. AB - BACKGROUND: The World Health Organization, in the year 2009, renamed Schistosomiasis haematobium disease, urinary schistosomiasis, as urogenital schistosomiasis. This study, sought to determine whether urogenital schistosomiasis endemic community members were aware of the broadened scope of the disease and associated certain reproductive health related signs and symptoms to S. haematobium infection. METHOD: This is a cross-sectional study in which 2,585 respondents aged 15-49 years from 30 riparian communities along the lower arm of the Volta lake were interviewed using a structured questionnaire; 24 focus group discussions were also conducted. Descriptive statistics were used to determine the frequency of responses for each question posed and Chi squared tests used to determine the associations between demographic variables and variables of interest. Binary logistic regression was used to predict the probability of a reported symptom as an indicator of urogenital schistosomiasis. Thematic analysis was used to examine narratives. RESULT: Ninety four percent of male respondents and 88.7 % of female respondents acknowledged schistosomiasis as a water-borne disease. Only 207 out of 1,096 subjects (18.9 %) responding to questionnaire agreed to the knowledge that urogenital schistosomiasis can have reproductive health implications. A significant difference in variation in this knowledge was found between males (14.5 %) and females (7.2 %) (p = 0.001). The study also found that, although knowledge on HIV was high, only 12.3 % of respondents knew that urogenital schistosomiasis could facilitate the acquisition of HIV. Women who reported to have ever suffered schistosomiasis were 1.3 and 1.5 times more likely to report vaginal discharge and vaginal itch. Sexual dysfunction (11.1 %) and urethral discharge (10.6 %) were the most frequently reported symptoms among males. CONCLUSION: The study finds very limited knowledge on the reproductive health consequences of the disease among endemic communities. It is recommended that health education on urogenital schistosomiasis should also include issues on symptoms of the disease, reproductive health consequences and HIV transmission. PMID- 27655031 TI - The effect of a chewing-intensive, high-fiber diet on oral halitosis: A clinical controlled study. AB - Tongue coating is the most common cause of oral halitosis and eating results in its reduction. Only limited data are available on the effect of different food items on tongue coating and halitosis. Therefore, the aim of this study was to investigate the effect of a single consumption of food with high fiber content versus low fiber content on halitosis parameters. Based on a randomized clinical cross-over study, 20 subjects were examined over a period of 2.5 hours after consumption of a high-fiber and a low-fiber meal. The determination of volatile sulfur compounds (VSC) was performed using a Halimeter, and the organoleptic assessment of halitosis was done on the basis of a distance index. The tongue coating was determined using a modified Winkel index, and the mouth sensation was evaluated subjectively by the subjects. In both the test and the control phase, a statistically significant reduction of all selected parameters was detected (p<0.05). Only for the organoleptic assessment of halitosis was a statistically significantly higher reduction found after consumption of a high-fiber meal compared to the control meal (p<0.05). In conclusion, the consumption of the meals in this study resulted in an at least 2.5-hour reduction of oral halitosis. The chewing-intensive (high-fiber) meal even resulted in a slightly higher reduction of oral halitosis in terms of organoleptic assessment (p<0.05). PMID- 27655033 TI - Kinase-Associated Phosphoisoform Assay: a novel candidate-based method to detect specific kinase-substrate phosphorylation interactions in vivo. AB - BACKGROUND: Protein kinases are important components of signalling pathways, and kinomes have remarkably expanded in plants. Yet, our knowledge of kinase substrates in plants is scarce, partly because tools to analyse protein phosphorylation dynamically are limited. Here we describe Kinase-Associated Phosphoisoform Assay, a flexible experimental method for directed experiments to study specific kinase-substrate interactions in vivo. The concept is based on the differential phosphoisoform distribution of candidate substrates transiently expressed with or without co-expression of activated kinases. Phosphorylation status of epitope-tagged proteins is subsequently detected by high-resolution capillary isoelectric focusing coupled with nanofluidic immunoassay, which is capable of detecting subtle changes in isoform distribution. RESULTS: The concept is validated by showing phosphorylation of the known mitogen-activated protein kinase (MAPK) substrate, ACS6, by MPK6. Next, we demonstrate that two transcription factors, WUS and AP2, both of which are shown to be master regulators of plant development by extensive genetic studies, exist in multiple isoforms in plant cells and are phosphorylated by activated MAPKs. CONCLUSION: As plant development flexibly responds to environmental conditions, phosphorylation of developmental regulators by environmentally-activated kinases may participate in linking external cues to developmental regulation. As a counterpart of advances in unbiased screening methods to identify potential protein kinase substrates, such as phosphoproteomics and computational predictions, our results expand the candidate-based experimental toolkit for kinase research and provide an alternative in vivo approach to existing in vitro methodologies. PMID- 27655034 TI - Fracture management in HIV positive individuals: a systematic review. AB - PURPOSE: Human immunodeficiency virus (HIV) infection could potentially play an important role in the management of fractures as they have been shown to affect fracture healing and the post-operative risk of implant sepsis. METHODS: A systematic review of the relevant literature was performed on PubMed and Scopus databases. Twenty-six studies were identified, critiqued and analysed accordingly. No randomised controlled trials were identified. RESULTS: HIV positivity was not shown to influence an individual's risk of early wound infection in operatively managed closed fractures. The rate of pin track infection in open injuries managed with external fixators was low. However, in open injuries managed with internal fixation, early wound infection rates were increased in the HIV-positive population compared to HIV-negative individuals. Regarding late implant infection, in closed fractures there appeared to be no increased risk of infection but there is limited evidence for open injuries. Additionally, further evidence is needed to establish if the rate of union in both open and closed fractures are influenced by HIV status. CONCLUSION: Overall, no evidence was found to suggest that surgical management of fractures in the HIV population should be avoided, and fixation of closed fractures in the HIV population appeared to be safe. The effect of anti-retroviral therapy is unclear and this should be further researched. However, based on the limited evidence, caution should be taken in the management of open fractures due to the potentially increased infection risk. The impact of anti-retroviral therapy on the outcomes of surgery needs further evaluation. PMID- 27655036 TI - Paget's Disease of the Vulva Treated with Imiquimod: Case Report and Systematic Review of the Literature. AB - BACKGROUND: Extramammary Paget's disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular growth pattern. Adjuvant treatment with the immunomodulator imiquimod may be suitable to avoid repeated and mutilating surgery. CASE PRESENTATION: We present the case of a 73-year-old woman with EPDV, initially treated with surgical resection and re-resection for involved margins. Final histology revealed Paget's disease of the left vulva with 8 cm in the largest diameter and again involved margins. Subsequently, topical therapy with imiquimod 5% cream twice weekly was applied for 3 months. Vulvoscopy and local biopsies confirmed complete remission (CR). Based on a literature search using PubMed and the Cochrane Central Register of Controlled Trials, 21 reports on the therapeutic efficacy of imiquimod in 70 women with EPDV have been published. Pooled rates of CR and partial remission were 71% (50/70) and 16% (11/70), respectively. There were 4 cases of disease progression under imiquimod and the therapy was generally well tolerated with mild to moderate local reactions in >50% of cases. CONCLUSION: EPDV is a rare genital neoplasia and may be successfully treated with the topical immunomodulator imiquimod. Specifically, adjuvant imiquimod is a feasible and efficacious treatment option for women with involved resection margins after surgery. PMID- 27655037 TI - Dispersion of positron emitting radioactive gases in a complex urban building array: a comparison of dose modelling approaches. AB - A radiological assessment was carried out on the release of positron-emitting radioactive gases from a roof-level stack at a central London site. Different modelling approaches were performed to investigate the range of radiation doses to representative persons. Contributions from plume inhalation, gamma shine and immersion to effective dose were taken into account. Dry and wet surface deposition on the roof, and exposure from contamination on the skin of roof workers, added only a mean 4.7% to effective dose and were neglected. A 1:200 scale model, consisting of the stack and surrounding buildings, was tested in a wind tunnel to simulate pollutant dispersion in the near-field region i.e. rooftop. Concentration field measurements in the wind tunnel were converted into effective dose, including for roof-workers installing glass cladding to the stack building. Changes in the building shape, from addition of the cladding layer, were investigated in terms of the near-field flow pattern and significant differences found between the two cases. Pollutant concentrations were also modelled using Air Dispersion Modelling System (ADMS) and the results used to calculate the effective dose using the same meteorological data set and source release terms. Sector averaged wind tunnel dose estimates were greater than the ADMS figure by approximately a factor of two to three. Different stack release heights were investigated in the wind tunnel and ADMS simulations in order to determine the best height for the replacement flue stack for the building. Other techniques were investigated: building wake models, modified Gaussian plume methods and uniform dilution into a hemispherical volume to show the wide variation in predicted dose possible with different approaches. Large differences found between simpler analytic approaches indicated that more robust radiological assessments, based on more complex modelling approaches, were required to achieve satisfactory estimates of radiation dose to representative groups in adjacent buildings and on the building rooftop. PMID- 27655038 TI - Evaluation of the Interplay between Uptake Transport and CYP3A4 Induction in Micropatterned Cocultured Hepatocytes. AB - Previously we assessed the inductive response of prototypical inducers in hepatocyte monocultures and the long-term coculture model HepatoPac using cryopreserved hepatocytes from the same donors. We noted that the rifampicin EC50 generated using the HepatoPac model corresponded better to the EC50 based on clinical data compared with data generated in the monoculture system. We postulated that there may be differences in the functioning of uptake transporters between the two systems that may have led to the EC50 difference. In this study, we characterized the functional activity of multiple uptake transporters in the two systems using cryopreserved hepatocytes from the same donors. Our data suggest that uptake transporter activity is higher in HepatoPac compared with the monoculture system. As a follow up to this study, we measured the intracellular concentrations of rifampicin and bosentan, which are known substrates of uptake transporters; we observed significantly higher intracellular concentrations of both compounds in HepatoPac relative to the monoculture system. This finding equated to lower cytochrome P450 isoform 3A4 (CYP3A4) EC50 values in the HepatoPac system compared with the monoculture system for both mRNA and activity. In parallel, no significant EC50 shift was observed for carbamazepine and phenytoin, which are not known to be substrates of uptake transporters. Our data suggest that next generation liver models such as HepatoPac may be a useful in vitro tool to quantitatively predict drug-drug interactions when it is known that the perpetrator is also a substrate of drug transporters. PMID- 27655043 TI - Semi-Paired Discrete Hashing: Learning Latent Hash Codes for Semi-Paired Cross View Retrieval. AB - Due to the significant reduction in computational cost and storage, hashing techniques have gained increasing interests in facilitating large-scale cross view retrieval tasks. Most cross-view hashing methods are developed by assuming that data from different views are well paired, e.g., text-image pairs. In real world applications, however, this fully-paired multiview setting may not be practical. The more practical yet challenging semi-paired cross-view retrieval problem, where pairwise correspondences are only partially provided, has less been studied. In this paper, we propose an unsupervised hashing method for semi paired cross-view retrieval, dubbed semi-paired discrete hashing (SPDH). In specific, SPDH explores the underlying structure of the constructed common latent subspace, where both paired and unpaired samples are well aligned. To effectively preserve the similarities of semi-paired data in the latent subspace, we construct the cross-view similarity graph with the help of anchor data pairs. SPDH jointly learns the latent features and hash codes with a factorization-based coding scheme. For the formulated objective function, we devise an efficient alternating optimization algorithm, where the key binary code learning problem is solved in a bit-by-bit manner with each bit generated with a closed-form solution. The proposed method is extensively evaluated on four benchmark datasets with both fully-paired and semi-paired settings and the results demonstrate the superiority of SPDH over several other state-of-the-art methods in term of both accuracy and scalability. PMID- 27655039 TI - Effects of a transdiagnostic unguided Internet intervention ('velibra') for anxiety disorders in primary care: results of a randomized controlled trial. AB - BACKGROUND: Internet-based cognitive-behavioural treatment (ICBT) for anxiety disorders has shown some promise, but no study has yet examined unguided ICBT in primary care. This randomized controlled trial (RCT) investigated whether a transdiagnostic, unguided ICBT programme for anxiety disorders is effective in primary care settings, after a face-to-face consultation with a physician (MD). We hypothesized that care as usual (CAU) plus unguided ICBT would be superior to CAU in reducing anxiety and related symptoms among patients with social anxiety disorder (SAD), panic disorder with or without agoraphobia (PDA) and/or generalized anxiety disorder (GAD). METHOD: Adults (n = 139) with at least one of these anxiety disorders, as reported by their MD and confirmed by a structured diagnostic interview, were randomized. Unguided ICBT was provided by a novel transdiagnostic ICBT programme ('velibra'). Primary outcomes were generic measures, such as anxiety and depression symptom severity, and diagnostic status at post-treatment (9 weeks). Secondary outcomes included anxiety disorder specific measures, quality of life, treatment adherence, satisfaction, and general psychiatric symptomatology at follow-up (6 months after randomization). RESULTS: CAU plus unguided ICBT was more effective than CAU at post-treatment, with small to medium between-group effect sizes on primary (Cohen's d = 0.41 0.47) and secondary (Cohen's d = 0.16-0.61) outcomes. Treatment gains were maintained at follow-up. In the treatment group, 28.2% of those with a SAD diagnosis, 38.3% with a PDA diagnosis, and 44.8% with a GAD diagnosis at pretreatment no longer fulfilled diagnostic criteria at post-treatment. CONCLUSIONS: The unguided ICBT intervention examined is effective for anxiety disorders when delivered in primary care. PMID- 27655040 TI - The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection. AB - Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually transported into bacteria via the phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), in which the phosphocarrier protein HPr (encoded by the ptsH gene) plays a central role. Although N. meningitidis possesses an incomplete PTS, HPr was found to be required for its virulence. We explored the role of HPr using bioluminescent wild-type and DeltaptsH strains in experimental infection in transgenic mice expressing the human transferrin. The wild-type MC58 strain was recovered at higher levels from the peritoneal cavity and particularly from blood compared to the DeltaptsH strain. The DeltaptsH strain provoked lower levels of septicemia in mice and was more susceptible to complement-mediated killing than the wild-type strain. We tested whether meningococcal structures impacted complement resistance and observed that only the capsule level was decreased in the DeltaptsH mutant. We therefore compared the transcriptomic profiles of wild type and DeltaptsH strains and identified 49 differentially expressed genes. The HPr regulon contains mainly hypothetical proteins (43%) and several membrane associated proteins that could play a role during host interaction. Some other genes of the HPr regulon are involved in stress response. Indeed, the DeltaptsH strain showed increased susceptibility to environmental stress conditions. Our data suggest that HPr plays a pleiotropic role in host-bacteria interactions most likely through the innate immune response that may be responsible for the enhanced clearance of the DeltaptsH strain from blood. PMID- 27655044 TI - Is "disease management" the answer to our problems? No! Population health management and (disease) prevention require "management of overall well-being". AB - BACKGROUND: Disease management programs based on the chronic care model have achieved successful and long-term improvement in the quality of chronic care delivery and patients' health behaviors and physical quality of life. However, such programs have not been able to maintain or improve broader self-management abilities or social well-being, which decline over time in chronically ill patients. Disease management efforts, population health management initiatives and innovative primary care solutions are still mainly focused on clinical and functional outcomes and health behaviors (e.g., smoking cessation, exercise, and diet) failing to address individuals' overall quality of life and well-being. Individuals' ability to achieve well-being can be assessed with great specificity through the application of social production function (SPF) theory. This theory asserts that people produce their own well-being by trying to optimize the achievement of instrumental goals (stimulation, comfort, status, behavioral confirmation, affection) that provide the means to achieve the larger, universal goals of physical and social well-being. DISCUSSION: A shift in focus from the management of physical function, disease limitations, and lifestyle behaviors alone to an approach that fosters self-management abilities such as self-efficacy and resource investment as well as overall quality of life, is urgently needed. Disease management interventions should be aimed at adequately addressing all difficulties chronically ill patients face in life, such as the effects of pain and fatigue on the ability to maintain a job and social life and to participate in activities promoting physical and social well-being. Patients' ability to maintain engagement in stimulating work and social activities with the people who are important to them may be even more important than aspects of disease self management such as blood pressure or glycemic control. Interventions should aim to make chronically ill patients capable of managing their own well-being and adequately addressing their needs in a broader sense. So, is disease management the answer to our problems in the time of aging populations and increased prevalence of unhealthy lifestyles, chronic illnesses, and comorbidity? No! Effective (disease) prevention, disease management, patient-centered care, and high-quality chronic care and/or population health management calls for management of overall well-being. PMID- 27655045 TI - Both canonical and non-canonical NF-kappaB activation contribute to the proliferative response of the middle ear mucosa during bacterial infection. AB - A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the middle ear mucosa. Activation of innate immune receptors during OM leads to the activation of NF-kappaB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-kappaB in mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-kappaB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-kappaB activation were regulated during OM, many with kinetics related to the time course of mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of NF-kappaB activation dominates mucosal hyperplasia during OM. PMID- 27655046 TI - Neutrophil azurophilic granule exocytosis is primed by TNF-alpha and partially regulated by NADPH oxidase. AB - Neutrophil (polymorphonuclear leukocyte) activation with release of granule contents plays an important role in the pathogenesis of acute lung injury, prompting clinical trials of inhibitors of neutrophil elastase. Despite mounting evidence for neutrophil-mediated host tissue damage in a variety of disease processes, mechanisms regulating azurophilic granule exocytosis at the plasma membrane, and thus release of elastase and other proteases, are poorly characterized. We hypothesized that azurophilic granule exocytosis would be enhanced under priming conditions similar to those seen during acute inflammatory events and during chronic inflammatory disease, and selected the cytokine TNF alpha to model this in vitro. Neutrophils stimulated with TNF-alpha alone elicited intracellular reactive oxygen species (ROS) generation and mobilization of secretory vesicles, specific, and gelatinase granules. p38 and ERK1/2 MAPK were involved in these components of priming. TNF-alpha priming alone did not mobilize azurophilic granules to the cell surface, but did markedly increase elastase release into the extracellular space in response to secondary stimulation with N-formyl-Met-Leu-Phe (fMLF). Priming of fMLF-stimulated elastase release was further augmented in the absence of NADPH oxidase-derived ROS. Our findings provide a mechanism for host tissue damage during neutrophil-mediated inflammation and suggest a novel anti-inflammatory role for the NADPH oxidase. PMID- 27655047 TI - Extracts of Morus nigra L. Leaves Standardized in Chlorogenic Acid, Rutin and Isoquercitrin: Tyrosinase Inhibition and Cytotoxicity. AB - Melanogenesis is a process responsible for melanin production, which is stored in melanocytes containing tyrosinase. Inhibition of this enzyme is a target in the cosmetics industry, since it controls undesirable skin conditions such as hyperpigmentation due to the overproduction of melanin. Species of the Morus genus are known for the beneficial uses offered in different parts of its plants, including tyrosinase inhibition. Thus, this project aimed to study the inhibitory activity of tyrosinase by extracts from Morus nigra leaves as well as the characterization of its chromatographic profile and cytotoxicity in order to become a new therapeutic option from a natural source. M. nigra leaves were collected, pulverized, equally divided into five batches and the standardized extract was obtained by passive maceration. There was no significant difference between batches for total solids content, yield and moisture content, which shows good reproducibility of the extraction process. Tyrosinase enzymatic activity was determined for each batch, providing the percentage of enzyme inhibition and IC50 values obtained by constructing dose-response curves and compared to kojic acid, a well-known tyrosinase inhibitor. High inhibition of tyrosinase activity was observed (above 90% at 15.625 MUg/mL). The obtained IC50 values ranged from 5.00 MUg/mL +/- 0.23 to 8.49 MUg/mL +/- 0.59 and were compared to kojic acid (3.37 MUg/mL +/- 0.65). High Performance Liquid Chromatography analysis revealed the presence of chlorogenic acid, rutin and, its major compound, isoquercitrin. The chromatographic method employed was validated according to ICH guidelines and the extract was standardized using these polyphenols as markers. Cytotoxicity, assessed by MTT assay, was not observed on murine melanomas, human keratinocytes and mouse fibroblasts in tyrosinase IC50 values. This study demonstrated the potential of M. nigra leaf extract as a promising whitening agent of natural source against skin hyperpigmentation. PMID- 27655049 TI - It's a Story, Not a Study: Writing an Effective Research Paper. PMID- 27655048 TI - modPDZpep: a web resource for structure based analysis of human PDZ-mediated interaction networks. AB - BACKGROUND: PDZ domains recognize short sequence stretches usually present in C terminal of their interaction partners. Because of the involvement of PDZ domains in many important biological processes, several attempts have been made for developing bioinformatics tools for genome-wide identification of PDZ interaction networks. Currently available tools for prediction of interaction partners of PDZ domains utilize machine learning approach. Since, they have been trained using experimental substrate specificity data for specific PDZ families, their applicability is limited to PDZ families closely related to the training set. These tools also do not allow analysis of PDZ-peptide interaction interfaces. RESULTS: We have used a structure based approach to develop modPDZpep, a program to predict the interaction partners of human PDZ domains and analyze structural details of PDZ interaction interfaces. modPDZpep predicts interaction partners by using structural models of PDZ-peptide complexes and evaluating binding energy scores using residue based statistical pair potentials. Since, it does not require training using experimental data on peptide binding affinity, it can predict substrates for diverse PDZ families. Because of the use of simple scoring function for binding energy, it is also fast enough for genome scale structure based analysis of PDZ interaction networks. Benchmarking using artificial as well as real negative datasets indicates good predictive power with ROC-AUC values in the range of 0.7 to 0.9 for a large number of human PDZ domains. Another novel feature of modPDZpep is its ability to map novel PDZ mediated interactions in human protein-protein interaction networks, either by utilizing available experimental phage display data or by structure based predictions. CONCLUSIONS: In summary, we have developed modPDZpep, a web-server for structure based analysis of human PDZ domains. It is freely available at http://www.nii.ac.in/modPDZpep.html or http://202.54.226.235/modPDZpep.html . REVIEWERS: This article was reviewed by Michael Gromiha and Zoltan Gaspari. PMID- 27655050 TI - Breaking the Silence: Time to Talk About Race and Racism. AB - Recent events in the United States have catalyzed the need for all educators to begin paying attention to and discovering ways to dialogue about race. No longer can health professions (HP) educators ignore or avoid these difficult conversations. HP students are now demanding them. Cultural sensitivity and unconscious bias training are not enough. Good will and good intentions are not enough. Current faculty development paradigms are no longer sufficient to meet the educational challenges of delving into issues of race, power, privilege, identity, and social justice.Engaging in such conversations, however, can be overwhelmingly stressful for untrained faculty. The authors argue that before any curriculum on race and racism can be developed for HP students, and before faculty members can begin facilitating conversations about race and racism, faculty must receive proper training through intense and introspective faculty development. Training should cover how best to engage in, sustain, and deepen interracial dialogue on difficult topics such as race and racism within academic health centers (AHCs). If such faculty development training-in how to conduct interracial dialogues on race, racism, oppression, and the invisibility of privilege-is made standard at all AHCs, HP educators might be poised to actualize the real benefits of open dialogue and change. PMID- 27655051 TI - How to Calculate a Survey Response Rate: Best Practices. PMID- 27655052 TI - Conceptual Frameworks to Guide Research and Development (R&D) in Health Professions Education. PMID- 27655053 TI - Key Sampling Issues in Quantitative Research in Health Professions Education. PMID- 27655054 TI - Ten Tips to Move From "Revisions Needed" to Resubmission. PMID- 27655055 TI - Common Qualitative Methodologies and Research Designs in Health Professions Education. PMID- 27655056 TI - Knowledge Translation and Implementation Science in Health Professions Education: Time for Clarity? PMID- 27655057 TI - The Tools of the Qualitative Research Trade. PMID- 27655058 TI - Creating 21st-Century Laboratories and Classrooms for Improving Population Health: A Call to Action for Academic Medical Centers. AB - Academic medical centers (AMCs) in the United States built world-class infrastructure to successfully combat disease in the 20th century, which is inadequate for the complexity of sustaining and improving population health. AMCs must now build first-rate 21st-century infrastructure to connect combating disease and promoting health. This infrastructure must acknowledge the bio-psycho social-environmental factors impacting health and will need to reach far beyond the AMC walls to foster community "laboratories" that support the "science of health," complementary to those supporting the "science of medicine"; cultivate community "classrooms" to stimulate learning and discovery in the places where people live, work, and play; and strengthen bridges between academic centers and these community laboratories and classrooms to facilitate bidirectional teaching, learning, innovation, and discovery.Private and public entities made deep financial investments that contributed to the AMC disease-centered approach to clinical care, education, and research in the 20th century. Many of these same funders now recognize the need to transform U.S. health care into a system that is accountable for population health and the need for a medical workforce equipped with the skills to measure and improve health. Innovative ideas about communities as centers of learning, the importance of social factors as major determinants of health, and the need for multidisciplinary perspectives to solve complex problems are not new; many are 20th-century ideas still waiting to be fully implemented. The window of opportunity is now. The authors articulate how AMCs must take bigger and bolder steps to become leaders in population health. PMID- 27655060 TI - Cons: Can liquid biopsy replace tissue biopsy?-the US experience. PMID- 27655062 TI - ? PMID- 27655061 TI - Constitutional Symptoms Trigger Diagnostic Testing Before Antibiotic Prescribing in High-Risk Nursing Home Residents. AB - OBJECTIVES: To evaluate the use of diagnostic testing before treating an infection in nursing home (NH) residents suspected of having a urinary tract infection (UTI) or pneumonia. DESIGN: Prospective longitudinal study nested within a randomized trial, using data from control sites. SETTING: Six NHs in southeast Michigan. PARTICIPANTS: NH residents with an indwelling urinary catheter, enteral feeding tube, or both (N = 162) with 695 follow-up visits (189 (28%) visits with an infection). MEASUREMENTS: Clinical and demographic data including information on incident infections, antibiotic use, and results of diagnostic tests-were obtained at study enrollment, after 14 days, and monthly thereafter for up to 1 year. RESULTS: One hundred (62%) NH residents had an incident infection requiring antibiotics, with substantial variations between NHs. In addition to presence of infection-specific symptoms, change in function was a significant predictor of ordering a chest X-ray to detect pneumonia (odds ratio (OR) = 1.7, P = .01). Similarly, change in mentation was a significant predictor of ordering a urinalysis (OR = 1.9, P = .02), chest X-ray (OR = 3.3, P < .001), and blood culture (OR = 2.3, P = .02). Antibiotics were used empirically, before laboratory results were available, in 50 of 233 suspected cases of UTI (21.5%) and 16 of 53 (30.2%) suspected cases of pneumonia. Antibiotics were used in 17% of visits without documented clinical or laboratory evidence of infection. CONCLUSION: Constitutional symptoms such as change in function and mentation commonly lead to diagnostic testing and subsequent antibiotic prescribing. Antibiotic use often continues despite negative test results and should be a target for future interventions. PMID- 27655063 TI - Hyperediting by ADAR1 of a new herpesvirus lncRNA during the lytic phase of the oncogenic Marek's disease virus. AB - Marek's disease virus, or Gallid herpesvirus 2 (GaHV-2), is an avian alphaherpesvirus that induces T-cell lymphoma in chickens. During transcriptomic studies of the RL region of the genome, we characterized the 7.5 kbp gene of the ERL lncRNA (edited repeat-long, long non-coding RNA), which may act as a natural antisense transcript (NAT) of the major GaHV-2 oncogene meq and of two of the three miRNA clusters. During infections in vivo and in vitro, we detected hyperediting of the ERL lncRNA that appeared to be directly correlated with ADAR1 expression levels. The ERL lncRNA was expressed equally during the lytic and latent phases of infection and during viral reactivation, but its hyperediting increased only during the lytic infection of chicken embryo fibroblasts. We also showed that chicken ADAR1 expression was controlled by the JAK/STAT IFN-response pathway, through an inducible promoter containing IFN-stimulated response elements that were functional during stimulation with IFN-alpha or poly(I:C). Like the human and murine miR-155-5p, the chicken gga-miR-155-5p and the GaHV-2 analogue mdv1-miR-M4-5p deregulated this pathway by targeting and repressing expression of suppressor of cytokine signalling 1, leading to the upregulation of ADAR1. Finally, we hypothesized that the natural antisense transcript role of the ERL lncRNA could be disrupted by its hyperediting, particularly during viral lytic replication, and that the observed deregulation of the innate immune system by mdv1-miR-M4-5p might contribute to the viral cycle. PMID- 27655064 TI - Conversion of simulated radioactive pollutant gas concentrations for a complex building array into radiation dose. AB - Methods used to convert wind tunnel and ADMS concentration field data for a complex building array into effective radiation dose were developed based on simulations of a site in central London. Pollutant source terms were from positron emitting gases released from a cyclotron and clinical PET radiotracer facility. Five years of meteorological data were analysed to determine the probability distribution of wind direction and speed. A hemispherical plume cloud model (both static and moving) was developed which enabled an expression of gamma ray dose, taking into account build-up factors in air, in terms of analytic functions in this geometry. The standard building wake model is presented, but this is extended and developed in a new model to cover the concentration field in the vicinity of a roof top structure recirculation zone, which is then related to the concentration in the main building wake zone. For all models presented the effective dose was determined from inhalation, positron cloud immersion and gamma ray plume contributions. Results of applying these models for determination of radiation dose for a particular site are presented elsewhere. PMID- 27655066 TI - Meningococcal carriage in children and young adults in the Philippines: a single group, cross-sectional study. AB - This cross-sectional prevalence study investigates meningococcal carriage for the first time in a Southeast Asian population. Posterior pharyngeal swabs were collected between August 2013 and March 2014 from 937 healthy Filipinos aged 5-24 years attending school or university in Manila. Of these, 35 were found to be carriers giving an overall carriage prevalence of 3.7% [95% confidence interval (CI) 2.6-5.2]. Carriage was associated with age (P < 0.001) and was highest (9.0%, 95% CI 5.5-13.8) in subjects aged 10-14 years, but was comparatively low (<3%) in all other age groups considered. This suggests that an immunization programme in the Philippines designed to reduce carriage acquisition and induce herd immunity may require a vaccine dose before the age of 10 years. Serogroup B was most commonly carried (65.7%, 95% CI 47.8-80.9), with a small number of carriers for serogroups C, Y and W also present. Two individuals (5.7%, 95% CI 0.7-19.2) who were simultaneously carrying multiple serogroups were identified. This exploratory study provides valuable insight into the asymptomatic carriage of Neisseria meningitidis in a healthy subset of the Filipino population and illustrates the importance of generating local carriage data. PMID- 27655065 TI - Effective treatment for prevention of post-operative adhesion after strabismus surgery in experimental rabbit model: 0.5 % tranilast ophthalmic solution. AB - BACKGROUND: Postoperative adhesion is one of the major complications of strabismus surgery and result in motility dysfunction that brings unpredictable surgical outcomes. However, there was no definitely accepted treatment method to prevent postoperative adhesion. METHODS: A prospective, randomized, controlled experimental animal study was performed. Both eyes of each of 14 New Zealand White rabbits underwent superior rectus muscle recession. After the surgical procedure, the subjects were divided randomly into two groups; 0.5 % tranilast ophthalmic solutions and fluoroquinolone antibiotic eye drops were administered to the group tranilast (N = 14), while the group control (N = 14) received fluoroquinolone eye drops only. Five weeks after surgery, we evaluated gross adhesions with a numeric score (0 to 4). In addition, histopathologic examination with hematoxylin & eosin staining, Masson's-trichrome staining, and anti transforming growth factor beta 1 (TGF-beta1) immuno-histochemical staining were done. RESULTS: The group tranilast showed significantly less gross adhesion and inflammation than the group control (P = 0.01 and P < 0.001, respectively). Masson's-trichrome staining revealed that post-operative collagen deposition was more prominent in the group control than the group tranilast (P < 0.001). Moreover, remarkable TGF-beta1 expression was observed in areas with excessive collagen deposition. CONCLUSIONS: Instillation of 0.5 % tranilast ophthalmic solution is a simple and effective method for preventing post-operative adhesion after strabismus surgery. PMID- 27655067 TI - Mouse RAGE Variant 4 Is a Dominant Membrane Receptor that Does Not Shed to Generate Soluble RAGE. AB - The receptor for advanced glycation end products (RAGE) is a multi-ligand, immunoglobulin-like receptor that has been implicated in aging-associated diseases. Recent studies have demonstrated that both human and murine Ager genes undergo extensive alternative splicing that generates multiple putative transcripts encoding different receptor isoforms. Except for the soluble isoform (esRAGE), the majority of putative RAGE isoforms remain unstudied. Profiling of murine Ager transcripts showed that variant transcript 4 (mRAGE_v4), the second most abundant transcript in lungs and multiple other tissues, encodes a receptor that lacks nine residues located within the C2 extracellular section close to the trans-membrane domain. We therefore characterized mRAGEV4 isoreceptor in comparison with the full-length mRAGE (mRAGEFL). Although differing in only nine residues, mRAGEFL and mRAGEV4 display very different cellular behaviors. While mRAGEFL undergoes constitutive, extensive shedding in the cell to generate sRAGE, mRAGEV4 hardly sheds. In addition, we found that while mRAGEFL can localize to both the plasma membrane and the endosome, mRAGEV4 is exclusively localized to the plasma membrane. These very different cellular localization patterns suggest that, in addition to their roles in sRAGE production, mRAGEFL and mRAGEV4 may play distinct, spatiotemporal roles in signaling and innate immune responses. Compared to mice, humans do not have the v4 transcript. Although hRAGE, like mRAGEFL, also localizes to the plasma membrane and the endosome, its rate of constitutive shedding is significantly lower. These observations provide valuable information regarding RAGE biology, and serve as a reference by which to create mouse models relating to human diseases. PMID- 27655069 TI - Centrifugal hypomelanosis: a new clinical phenotype of Malassezia infection. PMID- 27655070 TI - The Effects of Vitamin B in Depression. AB - Vitamins are dietary components which are necessary for life. They play a major role in health and their deficiency may be linked to symptoms of psychiatric disorders. B vitamins are required for proper functioning of the methylation cycle, monoamine oxidase production, DNA synthesis and the repair and maintenance of phospholipids. Vitamin B deficiency could influence memory function, cognitive impairment and dementia. In particular, vitamins B1, B3, B6, B9 and B12 are essential for neuronal function and deficiencies have been linked to depression. We discuss the causes of depression and the neurochemical pathways in depression. In particular, we provide evidence that vitamin B contributes to the complexity of depressive symptoms. PMID- 27655071 TI - Leucine-zipper and Sterile-alpha Motif Kinase (ZAK): A Potential Target for Drug Discovery. AB - Leucine-zipper and sterile-alpha motif kinase (ZAK) is a member of mixed-lineage kinase family (MLKs), which is considered as a new potential target for different physiological disorders, including myocardial hypertrophy and cardiac fibrosis, inflammation and cancer. However, the progress on its biological functions and small molecule inhibitors is limited. Only several multi-kinases inhibitors are reported to non-selectively bind with ZAK with various potencies. Herein, we provide an updated overview on the biological functions and small molecular inhibitors of ZAKs. PMID- 27655068 TI - Gram-Positive Bacteria with Probiotic Potential for the Apis mellifera L. Honey Bee: The Experience in the Northwest of Argentina. AB - Apis mellifera L. is one of the most important natural pollinators of significant crops and flowers around the world. It can be affected by different types of illnesses: american foulbrood, nosemosis, varroasis, viruses, among others. Such infections mainly cause a reduction in honey production and in extreme situations, the death of the colony. Argentina is the world's second largest honey exporter and the third largest honey producer, after China and Turkey. Given both the prominence of the honey bee in nature and the economic importance of apiculture in Argentina and the world, it is crucial to develop efficient and sustainable strategies to control honey bee diseases and to improve bee colony health. Gram-positive bacteria, such as lactic acid bacteria, mainly Lactobacillus, and Bacillus spp. are promising options. In the Northwest of Argentina, several Lactobacillus and Bacillus strains from the honey bee gut and honey were isolated by our research group and characterized by using in vitro tests. Two strains were selected because of their potential probiotic properties: Lactobacillus johnsonii CRL1647 and Bacillus subtilis subsp. subtilis Mori2. Under independent trials with both experimental and commercial hives, it was determined that each strain was able to elicit probiotic effects on bee colonies reared in the northwestern region of Argentina. One result was the increase in egg-laying by the queen which therefore produced an increase in bee number and, consequently, a higher honey yield. Moreover, the beneficial bacteria reduced the incidence of two important bee diseases: nosemosis and varroosis. These results are promising and extend the horizon of probiotic bacteria to the insect world, serving beekeepers worldwide as a natural tool that they can administer as is, or combine with other disease-controlling methods. PMID- 27655073 TI - Ellagitannins, gallotannins and their metabolites- the contribution to the anti inflammatory effect of food products and medicinal plants. AB - The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the anti-inflammatory potential of HT containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products' phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs' bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs' metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases. PMID- 27655072 TI - Synthesis of Pyrido-annelated Diazepines, Oxazepines and Thiazepines. AB - The immense amount of research on benzodiazepines resulted in the synthesis of heterocycle-fused diazepine derivatives with potential pharmacological activity. Pyridoazepines are recognized to be active in the central nervous system and have a comparable activity to the well-known benzodiazepines. This makes the synthesis and the study of pyridodiazepines an important research topic. This review comprises of the synthesis and activity of pyridodiazepines, pyridooxazepines and pyridothiazepines. Although these structures have a great similarity with benzodiazepines, much less work has been published on their synthesis or derivatization. Therefore, there is a need to further develop these classes of underexplored scaffolds, in search for new chemistry, new methodology and hence new biological features. PMID- 27655074 TI - Phytochemical and pharmacological activity profile of Crataegus oxyacantha L. (hawthorn) - A cardiotonic herb. AB - Crataegus oxyacantha L. (syn. C. rhipidophylla Gand.) (Rosaceae) is one of two medicinally recognized hawthorn species in European Pharmacopeia. Standardization of the extract prepared from the berry and flowers of the plant is required according to its oligomeric procyanidins. C. oxyacantha is well-known for its use in the treatment of various heart problems particularly, including heart failure in cases of declining cardiac performance equivalent to stages I and II of the New York Heart Association classification, angina pectoris, hypertension with myocardial insufficiency, mild alterations of cardiac rhythm, and atherosclerosis. C. oxyacantha has been reported to exert several other pharmacological activities such as hypotensive, antihyperlipidemic, antihyperglycemic, anxiolytic, immunomodulatory, and antimutagenic. Oligomeric procyanidins and flavone/flavonol types of flavonoids, which are considered to be the chief groups of active substances, phenolic acids, triterpenes, fatty acids, and sterols are present in the plant. The present review aims mainly to outline cardiotonic effect of C. oxyacantha as well as its brief phytochemistry. Numerous experiments and clinical studies have underlined cardiovascular efficacy of the plant through various mechanisms including positive inotropic and negative chronotropic effects, escalation in coronary blood flow and exercise tolerance, inhibition of the enzymes such as angiotensin-converting enzyme (ACE) and phosphodiesterase, anti-inflammatory and antihyperlipidemic effects, improving status of antioxidant enzymes, etc., which support its cardioactive efficacy. The plant possesses several other bioactivities for human health usually concomitant to its rich polyphenolic content. PMID- 27655075 TI - Quercetin is a useful medicinal compound showing various actions including control of blood pressure, neurite elongation and epithelial ion transport. AB - Quercetin has multiple potential to control various cell function keeping our body condition healthy. In this review article, we describe the molecular mechanism on how quercetin exerts its action on blood pressure, neurite elongation and epithelial ion transport based from a viewpoint of cytosolic Cl- environments, which is recently recognized as an important signaling factor in various types of cells. Recent studies show various roles of cytosolic Cl- in regulation of blood pressure and neurite elongation, and prevention from bacterial and viral infection. We have found the stimulatory action of quercetin on Cl- transporter, Na+-K+-2Cl- cotransporter 1 (NKCC1; an isoform of NKCC), which has been recognized as one of the most interesting, fundamental actions of quercetin. In this review article, based on this stimulatory action of quercetin on NKCC1, we introduce the molecular mechanism of quercetin on: 1) blood pressure, 2) neurite elongation, and 3) epithelial Cl- secretion including tight junction forming in epithelial tissues. 1) Quercetin induces elevation of the cytosolic Cl- concentration via activation of NKCC1, leading to anti-hypertensive action by diminishing expression of epithelial Na+ channel (ENaC), a key ion channel involved in renal Na+ reabsorption, while quercetin has no effects on the blood pressure with normal salt intake. 2) Quercetin also has stimulatory effects on neurite elongation by elevating the cytosolic Cl- concentration via activation of NKCC1 due to tubulin polymerization facilitated through Cl--induced inhibition of GTPase. 3) Further, in lung airway epithelia quercetin stimulates Cl- secretion by increasing the driving force for Cl- secretion via elevation of the cytosolic Cl- concentration: this leads to water secretion, participating in prevention of our body from bacterial and viral infection. In addition to transcellular ion transport, quercetin regulates tight junction function via enhancement of tight junction integrity by modulating expression and assembling tight junction-forming proteins. Based on these observations, it is concluded that quercetin is a useful medicinal compound keeping our body to be in healthy condition. PMID- 27655076 TI - Cocoa polyphenols: Chemistry, bioavailability and effects on cardiovascular performance. AB - This review gives an overview of the phenolic compounds composition of cocoa beans and their modification during manufacturing processes to the final products. Recently published papers dealing with the qualitative and quantitative analysis of the different classes of cocoa phenolic compounds will be discussed. Modifications of the qualitative profile and amount of phenolic compounds in cocoa after the main processes of production chain, fermentation, drying, roasting, and alkalization, will be described. The second part will focus on some of the biological effects described for cocoa phenolic compounds in vitro and in vivo. In particular, the effects of cocoa flavanols on cardiovascular health and endothelial function have been extensively investigated over the last decades, with interesting results from nutritional intervention trials and molecular studies. A few recent updates on the role of cocoa and chocolate consumption on sport performances will be reported. PMID- 27655077 TI - Characterization of Crude Oil Degrading Bacteria Isolated from Contaminated Soils Surrounding Gas Stations. AB - A total of twenty bacterial cultures were isolated from hydrocarbon contaminated soil. Of the 20 isolates, RAM03, RAM06, RAM13, and RAM17 were specifically chosen based on their relatively higher growth on salt medium amended with 4 % crude oil, emulsion index, surface tension, and degradation percentage. These bacterial cultures had 16S rRNA gene sequences that were most similar to Ochrobactrum cytisi (RAM03), Ochrobactrum anthropi (RAM06 and RAM17), and Sinorhizobium meliloti (RAM13) with 96 %, 100 % and 99 %, and 99 % similarity. The tested strains revealed a promising potential for bioremediation of petroleum oil contamination as they could degrade >93 % and 54 % of total petroleum hydrocarbons (TPHs) in a liquid medium and soil amended with 4 % crude oil, respectively, after 30 day incubation. These bacteria could effectively remove both aliphatic and aromatic petroleum hydrocarbons. In conclusion, these strains could be considered as good prospects for their application in bioremediation of hydrocarbon contaminated environment. PMID- 27655078 TI - Effects of Different Soil Amendments on Mixed Heavy Metals Contamination in Vetiver Grass. AB - Three different types of low cost soil amendments, namely, EDTA, elemental S and N-fertilizer, were investigated with Vetiver grass, Vetiveria zizanioides (Linn.) Nash growing under highly mixed Cd-Pb contamination conditions. A significant increase (p < 0.05) in Cd and Pb accumulation were recorded in the shoots of all EDTA and N-fertilizer assisted treatments. The accumulation of Cd in 25 mmol EDTA/kg soil and 300 mmol N/kg soil showed relatively higher translocation factor (1.72 and 2.15) and percentage metal efficacy (63.25 % and 68.22 %), respectively, compared to other treatments. However, it was observed that the increased application of elemental S may inhibit the availability of Pb translocation from soil-to-root and root-to-shoot. The study suggests that viable application of 25 mmol EDTA/kg, 300 mmol N/kg and 20 mmol S/kg soil have the potential to be used for soil amendment with Vetiver grass growing under contaminated mixed Cd-Pb soil conditions. PMID- 27655079 TI - Determination of Xylene and Toluene by Solid-Phase Microextraction Using Au Nanoparticles-Thiol Silane Film Coupled to Ion Mobility Spectrometry. AB - A simple, rapid and sensitive method for analysis of xylene and toluene was developed using the solid-phase microextraction (SPME) combined with ion mobilityspectrometry (IMS). Gold nanoparticles-thiol silane film (Au NPs-TSF) was applied as a newsorbent for SPME. Thiol silane film was formed on the surface of a stainless steel wire through incorporating Au nanoparticles during synthesis using sol-gel technique. The extraction properties of the fiber to xylene and toluene were examined, using a SPME device and thermal desorption ininjection port of IMS. The calibration graphs were linear in the range of 1.10-32.0 and 16.0-112.0 ppb for xylene and toluene, respectively. The detection limits for xylene and toluene were 0.7 and 8.0 ppb, respectively. The proposed method was applied without any considerable sample pretreatment and it was found to be simple enough to be strongly recommended for real sample analysis. PMID- 27655080 TI - Outcomes associated with observation versus short-stay admission among chest pain patients in the Veterans Health Administration. AB - BACKGROUND: To determine the extent to which 30- and 90-day hospital readmission and mortality rates differ as a function of whether a chest pain patient is placed in observation status or admitted to the hospital for a short-stay (<48 h). METHODS: Using 114,043 observation stays and short-stay admissions for chest pain at Veterans Health Administration hospitals between 2005 and 2013, we estimated event-level logistic regression models using a generalized estimating equation framework to predict 30 and 90-day readmissions and mortality as a function of whether the patient had an observation stay or a short-stay admission. We also adjusted for a variety of patient characteristics and unobserved time-invariant hospital factors. RESULTS: Relative to the short-stay inpatient group, veterans with chest pain who were placed in observation status were significantly more likely to be female (7.0 % vs. 6.4 %, White (76.6 % vs. 71.0 %, and from a rural area (28.3 % vs. 20.2 %). There were no other meaningful differences between the groups. Veterans with chest pain who were placed in observation status had 25 % lower odds of dying within 30 days (95 % confidence interval [CI]: 3 % - 43 %) and 12 % lower odds of a 30-day readmission (95 % CI: 6 % - 17 %) compared to those admitted as short-stay inpatients. Neither 90-day outcome was significantly associated with placement in observation status. Patient demographics were also important predictors of mortality and readmissions. CONCLUSIONS: There are clinically observable differences in outcomes between patients admitted to observation and those admitted as short stay inpatients. We find no evidence that the increase in observation stays reflects a lack of proper care for patients placed in observation status. PMID- 27655082 TI - Sins of Omission. PMID- 27655081 TI - Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination. AB - BACKGROUND: With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. METHODS: Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. RESULTS: Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination. Thus, the results revealed an unexpected disagreement between intersubtype similarity and breakpoint distribution, which were further confirmed by genetic similarity analysis. Our analysis reveals a critical conflict between results from natural HIV-1 isolates and those from HIV 1-based assay vectors in which genetic similarity has been shown to be a very critical factor promoting recombination. CONCLUSIONS: These results indicate the region with high-pairing probabilities may be a more fundamental factor affecting HIV-1 recombination than sequence similarity in natural HIV-1 infections. Our findings will be relevant in furthering the understanding of HIV-1 recombination mechanisms. PMID- 27655083 TI - Quiet Time for Mechanically Ventilated Patients in a Medical Intensive Care Unit. PMID- 27655084 TI - Work Re-Entry of RNs After Substance Use Disorder Treatment: A Grounded Theory Study. PMID- 27655085 TI - Internal Assets, Bullying, and Emotional Distress Among Young Adolescents. PMID- 27655086 TI - Intimate Partner Violence: Enhancing Vigilance of Screening, Treatment, and Referral in the Primary Care Setting. PMID- 27655087 TI - Applying the Evidence in Treatment of Acute Uncomplicated Bronchitis in Emergency Medicine. PMID- 27655088 TI - Implementing a Nurse-Driven Protocol to Manage Diabetic Patients in Hyperbarics. PMID- 27655089 TI - Adolescent Concussion: Post-Injury Assessment Relationships. PMID- 27655090 TI - An Examination of Nursing Care Quality Efficiency in U.S. Nursing Homes: Using Data Envelopment Analysis. PMID- 27655091 TI - Effect of Nurse Practitioner Visits on Health Outcomes in African American Teens With Asthma. PMID- 27655092 TI - E-Pain Reporter: A Digital Pain and Analgesic Diary for Home Hospice Care. PMID- 27655093 TI - An IL1RN Polymorphism Predicts Early Birth Among African American Women. PMID- 27655094 TI - Knowledge, Attitudes, and Perceptions of Tuberculosis Among Adults in Rural Maharashtra, India. PMID- 27655096 TI - Seeing Students Squirm: Student Nurses' Bullying Experiences in Clinical Settings. PMID- 27655095 TI - Testing a Protocol to Stop Ineffective Drug and Non-Drug Treatments. PMID- 27655097 TI - Social Determinants Documentation in Electronic Health Records With and Without Standardized Terminologies. PMID- 27655098 TI - In Memoriam: A. Robert Kagan, MD. PMID- 27655099 TI - A Retrospective Feasibility Study of Salvage Pelvic Nodal Radiation in 6 Patients With Biochemical Failure Following Prostate Fossa Radiation: An Alternative to Androgen Deprivation Therapy (ADT). AB - PURPOSE: To evaluate salvage pelvic nodal radiation as an alternative to androgen deprivation therapy (ADT) in patients with biochemical failure and lymph node recurrence following salvage prostate fossa radiation. METHODS: Six patients with biochemical failure and lymph node recurrence following prostate fossa radiation were treated with salvage pelvic nodal radiation therapy. A gross target volume was contoured using Choline PET/CT, CT, or MRI imaging. The clinical target volume included pelvic nodes. Avoidance structures were created using isodose lines from previous prostate fossa radiation plans. Radiation was delivered using IMRT or VMAT techniques. Failure was defined as a confirmed rise of prostate specific antigen (PSA) over 0.2 ng/mL. RESULTS: Four patients had presalvage PSA values <1 and 2 patients had PSAs >1. Dose to the clinical target volume was 54 to 60 Gy. The gross target volume dose was 60 to 73.6 Gy. One of the 2 patients with a high PSA received 6 months of concomitant ADT. Mean follow-up after RT for all patients was 24.9 months (range, 18.1 to 33.0 mo). All 5 patients with no ADT had significant PSA responses. PSA reduction was 80% (62% to 100%) of pre-RT PSA. At last follow-up, 2 patients with initial PSA<1 ng/mL remain free of biochemical progression at 33 and 20 months. Four patients have had PSA rise and meet criteria for failure. This included both patients with initial PSA values > 1. Duration of response before failure was 18.1 to 30.7 months. ADT for failure has been started in 1 patient. There was no grade >=2 GI or GU toxicity. CONCLUSIONS: Salvage lymph node irradiation for patients with early biochemical recurrence and radiologic evidence of pelvic nodal metastases is well tolerated and associated with a durable biochemical response and may be an alternative to or may delay the need for ADT in some patients. PMID- 27655100 TI - ERAT: A New ERA for Appendicitis Therapy? PMID- 27655101 TI - Role of Non-hepatic Medical Comorbidity and Functional Limitations in Predicting Mortality in Patients with HCV. AB - BACKGROUND: Medical comorbidities and functional status limitations are determinants of mortality in many chronic diseases. The extent to which survival in the rapidly aging cohort of patients with HCV is affected by these competing causes of mortality remains unclear. AIM: We sought to determine the effect of medical/functional comorbidities on survival after adjusting for liver disease severity in a cohort of patients with HCV infection. METHODS: We prospectively recruited consecutive patients from an HCV clinic 2009-2014. We calculated an index of survival (Schonberg Index, SI) based on age, gender, medical comorbidities, and functional status variables. We defined cirrhosis with the FibroSure test (F3/4-F4). We used multivariable Cox modeling to assess association between functional/survival measure and survival after adjustment for severity of liver disease. RESULTS: The cohort consisted of 1052 HCV patients. The average age was 56.8 years; 36 % had cirrhosis. The mean SI was 8.2 (SD = 2.7). During a mean follow-up of 5610 person-years, 102 (9.7 %) patients died. In unadjusted analysis, higher baseline SI predicted mortality (HR 1.17; 95 % CI 1.09-1.25). SI similarly predicted mortality in cirrhotic patients (HR 1.23, 95 % CI 1.13-1.34) and non-cirrhotic patients (HR 1.21, 95 % CI 1.08-1.36). This did not change after adjusting for age, drug use, or coronary artery disease. DISCUSSION: Comorbidities and functional limitations predict higher mortality in patients with HCV; this relationship is independent of cirrhosis. Use of general prognostic indices may help identify HCV patients at high risk for mortality, which could further guide clinical care in a manner not achievable with assessment of liver disease alone. PMID- 27655103 TI - Familial Risk of Biliary Tract Cancers: A Population-Based Study in Utah. AB - BACKGROUND AND OBJECTIVES: Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite. METHODS: BTC diagnosed between 1980 and 2011 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and gender-matched BTC-free controls were selected to form the comparison group for determining BTC risk in relatives using Cox regression analysis. RESULTS: Of the 1302 index patients diagnosed with BTC, 550 (42.2 %) were located in the gallbladder and 752 (57.8 %) were cholangiocarcinomas. There was no elevated risk of BTC (all subsites combined) in FDRs (HR 0.94, 95 % CI 0.29-3.0), SDRs (HR 0.25, 95 % CI 0.06-1.03), and FCs (HR 0.96, 95 % CI 0.61 1.51) of BTC cases compared to cancer-free controls. Similarly, no increased familial risk of GBC or CC was found in relatives of BTC patients stratified by tumor subsite compared to relatives of controls. CONCLUSIONS: Relatives of BTC patients are not at an increased risk of GBC or CC in a statewide population. This suggests that biliary tract cancer risk is not associated with a familial predisposition and may be mitigated more strongly by environmental modifiers. PMID- 27655104 TI - Rifaximin Decreases the Incidence and Severity of Acute Kidney Injury and Hepatorenal Syndrome in Cirrhosis. AB - BACKGROUND: While the effects of rifaximin have been shown to be protective against acute kidney injury (AKI) and hepatorenal syndrome (HRS) in alcohol induced cirrhosis, its long-term effects on the renal function of other cirrhotic patients are unknown. AIM: To examine the long-term effects of rifaximin on the renal function of patients with cirrhosis from various etiologies. METHODS: In a retrospective study, we examined cirrhotic patients at the University of Chicago Liver Clinic from January 1, 2011, to December 31, 2014. The study enrolled patients on rifaximin for >=90 days, who were then matched by age, gender, and MELD score to a control group. Patients with malignancy and renal replacement therapy (RRT) at baseline were excluded. Data were censored at the last follow up, termination of rifaximin therapy, initiation of RRT, death, or liver transplant. RESULTS: Eighty-eight rifaximin cases were identified and matched to 88 control cases. Baseline characteristics were similar, with the exceptions of more prevalent long-term midodrine use (>=90 days) (17.0 vs 4.5 %, p = 0.01) and baseline ascites (37.5 vs 23.8 %, p = 0.05) in the rifaximin group. There was no difference in the frequency of infections, deaths, liver transplants, or hospitalizations. After controlling for cofounders, the incidence rate ratio of AKI (IRR 0.71, p = 0.02) and HRS (IRR 0.21, p = 0.02), as well as the risk of requiring RRT (OR 0.23, p = 0.01), was lower in the rifaximin group. CONCLUSIONS: Long-term use of rifaximin is associated with a decrease incidence of AKI and HRS and a decrease risk of requiring RRT in a general population of cirrhotic patients. PMID- 27655106 TI - Relationship Between Frailty and Oral Function in Community-Dwelling Elderly Adults. AB - OBJECTIVES: To determine the standard values of and age-related changes in objective oral function of healthy older people; compare oral function of robust, prefrail, and frail older people; and determine the association between oral function and frailty. DESIGN: Cross-sectional analysis. SETTING: General community. PARTICIPANTS: Elderly adults (>=65) from the Obu Study of Health Promotion for the Elderly were included and assigned to the robust, prefrail, and frail groups (N = 4,720). MEASUREMENTS: Each participant underwent detailed physical testing to assess frailty. The frailty phenotype was defined according to the presence of limitations in three or more of the following five domains: mobility, strength, endurance, physical activity, and nutrition. The numbers of present teeth and functional teeth were counted, and occlusal force, masseter muscle thickness, and oral diadochokinesis (ODK) rate were measured, along with sociodemographic and functional status, comorbidities, and blood chemistry. RESULTS: The number of present teeth, occlusal force, masseter muscle thickness, and ODK rate decreased with age. The frail group had significantly fewer present teeth (women aged >=70), lower occlusal force (women aged >=70; men aged >=80), lower masseter muscle thickness, and lower ODK rate than the robust group. Multivariate analysis indicated that age, Geriatric Depression Scale score, skeletal muscle mass index, Mini-Mental State Examination score, hypertension, diabetes mellitus, albumin and triglyceride levels, and oral function were significantly associated with frailty. CONCLUSION: Age-related differences in oral function were found in older adults. Moreover, frail older individuals had significantly poorer oral function than prefrail and robust individuals. The risk of frailty was associated with lower occlusal force, masseter muscle thickness, and ODK rate. PMID- 27655102 TI - B Cell-Activating Factor (BAFF)-Targeted B Cell Therapies in Inflammatory Bowel Diseases. AB - Inflammatory bowel diseases (IBD) involve dysregulated immune responses to gut antigens in genetically predisposed individuals. While a better elucidation of IBD pathophysiology has considerably increased the number of treatment options, the need for more effective therapeutic strategies remains a pressing priority. Defects of both non-hematopoietic (epithelial and stromal) and hematopoietic (lymphoid and myeloid) cells have been described in patients with IBD. Within the lymphoid system, alterations of the T cell compartment are viewed as essential in the pathogenesis of IBD. However, growing evidence points to the additional perturbations of the B cell compartment. Indeed, the intestinal lamina propria from IBD patients shows an increased presence of antibody-secreting plasma cells, which correlates with enhanced pro-inflammatory immunoglobulin G production and changes in the quality of non-inflammatory IgA responses. These B cell abnormalities are compounded by the emergence of systemic antibody responses to various autologous and microbial antigens, which predates the clinical diagnosis of IBD and identifies patients with complicated disease. It is presently unclear whether such antibody responses play a pathogenetic role, as B cell depletion with the CD20-targeting monoclonal antibody rituximab did not ameliorate ulcerative colitis in a clinical trial. However, it must be noted that unresponsiveness to rituximab is also observed also in some patients with autoimmune disorders usually responsive to B cell-depleting therapies. In this review, we discussed mechanistic aspects of B cell-based therapies and their potential role in IBD with a special interest on BAFF and BAFF-targeting therapies buoyed by the success of anti-BAFF treatments in rheumatologic disorders. PMID- 27655107 TI - Swedish snuff (snus) and its effects on oral health: an update AB - Swedish snus (smokeless moist tobacco) is becoming increasingly popular in Switzerland. Consumption and import of snus are permitted in Switzerland, however, sales were prohibited in 2004 by the European Court. Snus is an addictive nicotine containing product, which additionally contains carcinogenic nitrosamines. Both consumers and oral health professionals are lacking important information on the health consequences. The present paper therefore reviews the impact of snus consumption on oral health. For all snus consumers and particularly for adolescents, more detailed information should be provided by oral health professionals. Specifically with heavy snus users, more frequent follow-up is recommended to detect potential precancerous lesions or neoplasias in early stages. PMID- 27655105 TI - Siglec-7 as a Novel Biomarker to Predict Mortality in Decompensated Cirrhosis and Acute Kidney Injury. AB - BACKGROUND: Patients with decompensated cirrhosis have high morbidity and are commonly hospitalized with acute kidney injury. AIMS: We examined serum levels of Siglec-7, a transmembrane receptor that regulates immune activity, as a biomarker for mortality in patients with cirrhosis and acute kidney injury. METHODS: Serum Siglec-7 was measured in hospitalized patients with cirrhosis and acute kidney injury, as well as in reference groups with acute liver injury/acute kidney injury, cirrhosis without acute kidney injury, and sepsis without liver disease. Clinical characteristics and subsequent outcomes were examined using univariate and multivariable analyses according to initial Siglec-7 levels. Primary outcome was death by 90 days. RESULTS: One hundred twenty-eight subjects were included, 92 of which had cirrhosis and acute kidney injury and were used in the primary analysis. Average Model for End-Stage Liver Disease (MELD) score was 24 [95 % CI 23, 26], and serum creatinine was 2.5 [2.2, 2.8] mg/dL at the time Siglec-7 was measured. After adjusting for age and MELD score, high serum Siglec-7 level predicted mortality with a hazard ratio of 1.96 [1.04, 3.69; p = 0.04]. There was no difference in Siglec-7 levels by etiology of AKI (p = 0.24). Addition of serum Siglec-7 to MELD score improved discrimination for 90-day mortality [category free net reclassification index = 0.38 (p = 0.04); integrated discrimination increment = 0.043 (p = 0.04)]. CONCLUSION: Serum Siglec-7 was associated with increased mortality among hospitalized patients with cirrhosis and acute kidney injury. Addition of Siglec-7 to MELD score may increase discrimination to predict 90-day mortality. PMID- 27655109 TI - Pros: Can tissue biopsy be replaced by liquid biopsy? PMID- 27655108 TI - MYD88 and functionally related genes are associated with multiple infections in a model population of Kenyan village dogs. AB - The purpose of this study was to seek associations between immunity-related molecular markers and endemic infections in a model population of African village dogs from Northern Kenya with no veterinary care and no selective breeding. A population of village dogs from Northern Kenya composed of three sub-populations from three different areas (84, 50 and 55 dogs) was studied. Canine distemper virus (CDV), Hepatozoon canis, Microfilariae (Acantocheilonema dracunculoides, Acantocheilonema reconditum) and Neospora caninum were the pathogens studied. The presence of antibodies (CDV, Neospora), light microscopy (Hepatozoon) and diagnostic PCR (Microfilariae) were the methods used for diagnosing infection. Genes involved in innate immune mechanisms, NOS3, IL6, TLR1, TLR2, TLR4, TLR7, TLR9, LY96, MYD88, and three major histocompatibility genes class II genes were selected as candidates. Single nucleotide polymorphism (SNP) markers were detected by Sanger sequencing, next generation sequencing and PCR-RFLP. The Fisher's exact test for additive and non-additive models was used for association analyses. Three SNPs within the MYD88 gene and one TLR4 SNP marker were associated with more than one infection. Combined genotypes and further markers identified by next generation sequencing confirmed associations observed for individual genes. The genes associated with infection and their combinations in specific genotypes match well our knowledge on their biological role and on the role of the relevant biological pathways, respectively. Associations with multiple infections observed between the MYD88 and TLR4 genes suggest their involvement in the mechanisms of anti-infectious defenses in dogs. PMID- 27655110 TI - The effects of iodine blocking on thyroid cancer, hypothyroidism and benign thyroid nodules following nuclear accidents: a systematic review. AB - A potential radiation protection method to reduce the risk of adverse health outcomes in the case of accidental radioactive iodine release is the administration of potassium iodide (KI). Although KI administration is recommended by WHO's Guidelines for Iodine Prophylaxis following Nuclear Accidents, a systematic review of the scientific evidence for the guidelines is lacking. Therefore, this study aims to systematically review the effects of KI administration in the case of accidental radioactive iodine release on thyroid cancer, hypothyroidism and benign thyroid nodules. We applied standard systematic review methodology for a search of the literature, selection of eligible studies, data extraction, assessment of risk of bias, assessment of heterogeneity, data synthesis, and the assessment of the quality of the evidence. We searched MEDLINE (via PubMed) and EMBASE. We found one cross-sectional study, one analytic cohort study and two case-control studies relating to our question. The number of participants ranged from 886-12 514. Two studies were conducted in children and two other studies in children and adults. It was not possible to conduct a meta analysis. We identified low to very low-quality evidence that KI administration after a nuclear accident resulted in a reduction of the risk of thyroid cancer in children; however, the KI administration and dose was not well described in the studies. None of the studies investigated the effects of KI administration in the case of a nuclear accident on hypothyroidism and benign thyroid nodules. Low to very low-quality evidence suggests that KI intake following a nuclear accident may reduce the risk of thyroid cancer in children. No conclusions can be drawn about the effectiveness of KI intake with respect to the prevention of hypothyroidism and benign thyroid nodules. PMID- 27655111 TI - Age-related hearing loss in older adults with cognitive impairment. AB - BACKGROUND: Hearing loss can impair effective communication between caregivers and individuals with cognitive impairment. However, hearing loss is not often measured or addressed in care plans for these individuals. The aim of this study is to measure the prevalence of hearing loss and the utilization of hearing aids in a sample of individuals with cognitive impairment in a tertiary care memory clinic. METHODS: A retrospective review of 133 charts of individuals >50 years who underwent hearing assessment at a tertiary care memory clinic over a 12-month period (June 2014-June 2015) was undertaken. Using descriptive statistics, the prevalence of hearing loss was determined and associations with demographic variables, relevant medical history, cognitive status, and hearing aid utilization were investigated. RESULTS: Results indicate that hearing loss is highly prevalent among this sample of cognitively impaired older adults. Sixty percent of the sample had at least a mild hearing loss in the better hearing ear. Among variables examined, age, MMSE, and medical history of diabetes were strongly associated with hearing impairment. Hearing aid utilization increased in concordance with severity of hearing loss, from 9% to 54% of individuals with a mild or moderate/severe hearing loss, respectively. CONCLUSIONS: Hearing loss is highly prevalent among older adults with cognitive impairment. Despite high prevalence of hearing loss, hearing aid utilization remains low. Our study highlights the importance of hearing evaluation and rehabilitation as part of the cognitive assessment and care management plan in this vulnerable population. PMID- 27655112 TI - Low-dose second-generation oral contraceptives are associated with the lowest increased risk of cardiovascular adverse effects. PMID- 27655113 TI - Social support plays a role in the attitude that people have towards taking an active role in medical decision-making. AB - BACKGROUND: There is a growing emphasis towards including patients in medical decision-making. However, not all patients are actively involved in such decisions. Research has so far focused mainly on the influence of patient characteristics on preferences for active involvement. However, it can be argued that a patient's social context has to be taken into account as well, because social norms and resources affect behaviour. This study aims to examine the role of social resources, in the form of the availability of informational and emotional support, on the attitude towards taking an active role in medical decision-making. METHODS: A questionnaire was sent to members of the Dutch Health Care Consumer Panel (response 70 %; n = 1300) in June 2013. A regression model was then used to estimate the relation between medical and lay informational support and emotional support and the attitude towards taking an active role in medical decision-making. RESULTS: Availability of emotional support is positively related to the attitude towards taking an active role in medical decision-making only in people with a low level of education, not in persons with a middle and high level of education. The latter have a more positive attitude towards taking an active role in medical decision-making, irrespective of the level of emotional support available. People with better access to medical informational support have a more positive attitude towards taking an active role in medical decision making; but no significant association was found for lay informational support. CONCLUSIONS: This study shows that social resources are associated with the attitude towards taking an active role in medical decision-making. Strategies aimed at increasing patient involvement have to address this. PMID- 27655115 TI - A home-based exercise intervention for caregivers of persons with dementia: study protocol for a randomised controlled trial. AB - BACKGROUND: Family members, who provide the majority of care for persons with dementia, are especially vulnerable to developing depression. Interventions targeting their depressive symptoms have been proposed but their efficacies vary considerably. It has been suggested that interventions carried out in the home setting and involving both caregivers and care recipients are more efficacious. This study aims to compare the efficacy of a home-based structured exercise programme involving both persons with dementia and their caregivers with nonexercise social contact control in treating depression among caregivers. METHODS/DESIGN: This is a parallel-group, assessor-blind, randomised controlled trial. A total of 136 caregiver-care-recipient dyads (i.e. 272 participants in total) will be recruited and randomly allocated to either a home-based structured exercise (sitting Tai Chi) group or a social contact control group. The trial comprises a 3-month intervention phase followed by an extended observation phase of another 3 months. All participants will be assessed at baseline, 6th week, 12th week and 24th week. The primary outcome will be the reduction in depression among caregivers as measured by the Hamilton Rating Scale for Depression. The secondary outcomes will be burden, quality of life, cognitive performance and balance ability of the caregivers, as well as the neuropsychiatric symptoms, cognitive function, balance and functional abilities of the persons with dementia. We will also examine whether the brain-derived neurotrophic factor gene modulates mood changes in response to exercise. DISCUSSION: The findings offer a potential avenue of intervention by providing a low-cost, safe and effective treatment for depression among dementia caregivers, which may in turn also benefit the care recipients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02132039 , registered on 28 April 2014. PMID- 27655114 TI - Treatment of Men for "Low Testosterone": A Systematic Review. AB - Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of "low testosterone" (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation did not show consistent benefit for cardiovascular risk, sexual function, mood and behavior, or cognition. Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo. Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido. Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function. Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality, psychological well-being, or mood. The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials. PMID- 27655117 TI - Reactive Eccrine Glands Hyperplasia in Vascular Proliferations. PMID- 27655116 TI - HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis. AB - INTRODUCTION: HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age associated diseases and mortality. Our goals were to use a single cohort of HIV infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality. METHODS: This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P<=0.2 in bivariate analysis were included in multivariate models. RESULTS: No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001), male gender (P = 0.04), total pack-years smoked (P<0.001), alcohol consumption in the past year (P = 0.12), and asthma (P = 0.08) were all associated (P<=0.2) with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (beta = -0.0621, 95% CI -0.113 to -0.011, P = 0.02). Shortened telomeres were not associated with TB or short-term mortality. CONCLUSIONS: The association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be involved in age associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging. PMID- 27655118 TI - CD30 Positive Lymphomatoid Angiocentric Drug Reactions: Characterization of a Series of 20 Cases. AB - INTRODUCTION: Lymphomatoid drug reactions are atypical T cell cutaneous lymphocytic infiltrates induced by pharmacological therapy. Due to phenotypic abnormalities, clonality, and their close clinical and morphologic resemblance to T cell lymphomas, these eruptions have been categorized as drug-associated reversible granulomatous T cell dyscrasias. DESIGN: A total of 20 cases were encountered in which a diagnosis of CD30 lymphomatoid drug reaction was rendered. RESULTS: There were 11 women and 9 men ranging from 31 to 86 years of age presenting with a sudden onset often generalized cutaneous papular eruption. Two patients had vasculitic lesions. In all cases, a positive drug history was elicited and in most the initiation of the drug was temporally associated with the cutaneous eruption. Among the implicated drugs were statins (6 cases), immunomodulators (4 cases), ACE inhibitors (3 cases), antibiotics (3 cases), chemotherapy agents (3 cases), and antidepressants (1 case). Biopsies demonstrated a similar morphology, namely a superficial angiocentric lymphocytic infiltrate containing many immunoblasts. Tissue eosinophilia, interface dermatitis, and supervening eczematous changes in the overlying epidermis were observed in most cases. In all cases, the angiocentric infiltrate was highlighted by CD3, CD30, and CD4. Cytotoxic protein granule expression or monoclonality was not observed. In all cases, there was improvement or complete regression of the eruption upon drug modulation. CONCLUSION: The CD30 positive lymphomatoid angiocentric drug reaction poses a diagnostic challenge because of its close resemblance to type A lymphomatoid papulosis and potential confusion with a peripheral T cell lymphoma with large cell transformation. PMID- 27655119 TI - Restrained Terminal Differentiation and Sustained Stemness in Neonatal Skin by Ha Ras and Bcl-2. AB - Nonmelanoma skin cancer is the most frequently diagnosed cancer in the United States. Deregulation of bcl-2 and ras family members is commonly observed in nonmelanoma skin cancer. It has been previously demonstrated that simultaneous bcl-2 and Ha-ras gene expression in keratinocytes results in resistance to cell death induced by ultraviolet radiation and enhanced multistep skin carcinogenesis. In this study, we aimed to elucidate the central roles of Ha-Ras and Bcl-2 in maintaining epidermal homeostasis. To assess the effect of deregulated Ha-Ras and Bcl-2 on skin differentiation, we have generated skin specific transgenic mouse model constitutively expressing both oncogenic Ha-Ras and Bcl-2. Ectopic expression of Ha-Ras and Bcl-2 in newborn double transgenic epidermal keratinocytes induced abnormal epidermal differentiation accompanied by increased cell proliferation and suppressed apoptotic cell death, which resulted in thickened and wrinkled skin morphology in neonate skins. Expression of epidermal differentiation marker cytokeratin 1 was decreased. Expression of other differentiation markers loricrin and filaggrin was also decreased and delayed to be detected only in the upper stratum granulosum, whereas the proliferative markers cytokeratin 14 and cytokeratin 6, which are expressed in constitutively proliferative basal layer and stem cell niches such as hair follicles or neoplastic lesions, respectively, were highly expressed. The abnormal expression of epidermal cytokeratins suggests that Ha-Ras and Bcl-2 suppress the terminal differentiation and sustain the stem cell-like features in epidermal keratinocytes. PMID- 27655121 TI - Detection of Merkel Cell Polyoma Virus and Beta Human Papillomavirus in Multiple Eccrine Poromas in a Patient With Acute Leukemia Treated With Stem Cell Transplant. PMID- 27655120 TI - Extraskeletal Myxoid Chondrosarcoma of the Foot Clinically Mimicking Plantar Fibromatosis. AB - Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma usually presenting in proximal extremities of middle-aged men. The authors discuss a unique case of EMC, localized in the plantar foot of a 76-year-old woman, clinically suspected as plantar fibromatosis. It is important to avoid misdiagnosis of EMC because of their propensity for late recurrence and their metastatic potential. PMID- 27655122 TI - Osteogenic Melanoma With Desmin Expression. AB - BACKGROUND: Osteogenic differentiation is rarely seen in melanomas, when it occurs it is mainly in acral lesions. METHODS: We report a case of an osteogenic melanoma in a 49-year-old woman who presented with a pigmented lesion in the subungueal region of her left hallux. The lesion was ulcerated and infiltrated until the deep dermis without bone involvement. RESULTS: The tumor was composed of pleomorphic atypical epithelioid and fusiform cells disposed in nests or cords, with vesicular nuclei and prominent central nucleoli. Focal lentiginous proliferation of large atypical melanocytes was present along the dermoepidermal junction. Areas of osteoid matrix focally mineralized were disposed in trabeculae, and there were islands of neoplastic cells. Immunohistochemistry revealed strong expression of S-100 protein and, unexpectedly, of desmin. Focal expression of Melan-A, microphthalmia transcription factor, and HMB-45 is also revealed. Mutations in BRAF and NRAS genes were not present. The patient was submitted to an amputation of the left hallux with negative sentinel lymph node. CONCLUSION: The importance of recognizing osteogenic melanoma is based on difficulties for histologic recognition and its differentials diagnosis. PMID- 27655123 TI - Living on the Edge: Diagnosing Sarcomatoid Melanoma Using Histopathologic Cues at the Edge of a Dedifferentiated Tumor: A Report of 2 Cases and Review of the Literature. AB - Sarcomatoid melanoma is a rare type of melanoma lacking typical histologic features of melanoma and often lacks expression of S100 protein and melanocyte specific markers. Given the rarity of this entity, its clinicopathologic findings are not well defined. We report 2 cases of sarcomatoid melanoma received in consultation: a 65-year-old woman with a right breast mass and a 62-year-old man with a left plantar heel mass. Both lesions were ulcerated, pedunculated, highly cellular proliferations of atypical spindle cells arranged as fascicles and/or sheets. The tumor cells of the breast mass expressed CD10 and vimentin diffusely but S100 protein only focally. The tumor cells of the heel mass lacked expression of melanocytic markers altogether, except for weak, very focal S100 protein expression. At the junctional edge of the breast mass and in the ulcer base of the heel mass, focal precursor melanoma was present and exhibited melanocytic differentiation. We report these cases to emphasize the importance of meticulous histologic inspection at the lesion's edge and/or ulcer base to correctly identify the conventional precursor melanoma in these rare lesions to ensure appropriate diagnosis and subsequent clinical management as treatment options may be significantly different from those offered for sarcomas. PMID- 27655124 TI - Cysticercosis of the Pectoralis Major: A Case Report and Review of Literature. AB - Cysticercosis is a condition caused by the encysted larval form of Taenia solium (pork tapeworm). The commonest system affected is the central nervous system. Symptomatic primary muscle involvement is a rare phenomenon. We present a case of a 19-year-old male who presented with a solitary cystic swelling in the right infraclavicular area. Magnetic resonance imaging revealed a cystic mass in the right pectoralis major muscle. The cyst was excised and submitted for histopathology. The diagnosis of cysticercosis was confirmed on histopathology of the excised cyst. PMID- 27655125 TI - Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D-40 and MITF1 in Primary Cutaneous Melanoma: Beware of MITF1 Specificity and Sensitivity in Unusual Melanoma Subtypes. PMID- 27655126 TI - An Immunohistochemical Study of Anogenital Mammary-Like Glands. AB - Although the normal histology of anogenital mammary-like glands (AGMLG) has been studied, no systemic investigation has been performed on the immunoprofile of these structures. We studied intact AGMLG with a broad panel of antibodies. The immunoprofile of AGMLG is similar to that of a normal breast tissue, and there are similarities to eccrine glands and coils about cytokeratin expression. Our immunohistochemical data may contribute to understanding of the pathogenesis of lesions arising from AGMLG. PMID- 27655127 TI - An Epidemic Outbreak of Cutaneous Leishmaniasis Presenting as Suppurative Folliculitis: A Study of 6 Cases. AB - Folliculitis is defined as the inflammation of the follicles. The most common cause of folliculitis is infection. Here, we report an unusual cause of suppurative infundibulitis-which had not yet been described in the literature-due to Leishmania infection, and exemplified by 6 cases that occurred in the setting of an epidemic outbreak. The 6 individuals were immigrants from Morocco. Most of them were men (4 men and 2 women), and most of them were less than 30 years old (apart from one 40-year-old woman). In all cases, a cutaneous biopsy was performed. There was a granulomatous folliculitis with suppurative granulomas in all the cases. All cases showed prominence of plasma cells in the inflammatory infiltrate, and leishmanias were found in all cases. They were mainly seen in the abscessified central areas. The amount of organisms varied from a few to a moderate amount. They were stained by the anti-CD1a antibody (Novocastra) and by a polyclonal homemade anti-leishmania antibody. In addition, in 1 case, microbiological culture was performed, and Leishmania major was demonstrated as the causative agent of the infection. PMID- 27655128 TI - ? AB - Bulk-fill resin composites represent an innovative class of dental composite materials, developed to simplify and expedite the restoration process. They can be adequately photopolymerized up to 4?5mm composite thickness and therefore permit a more economical restorative approach as compared to conventional resin composites. The current paper summarizes the most important facts on bulk-fill composite materials and provides recommendations for the successful use of these materials in daily practice based on up-to-date in vitro and in vivo research. PMID- 27655129 TI - MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling. AB - : MEK inhibitors have limited efficacy in treating RAS-RAF-MEK pathway-dependent cancers due to feedback pathway compensation and dose-limiting toxicities. Combining MEK inhibitors with other targeted agents may enhance efficacy. Here, codependencies of MEK, TAK1, and KRAS in colon cancer were investigated. Combined inhibition of MEK and TAK1 potentiates apoptosis in KRAS-dependent cells. Pharmacologic studies and cell-cycle analyses on a large panel of colon cancer cell lines demonstrate that MEK/TAK1 inhibition induces cell death, as assessed by sub-G1 accumulation, in a distinct subset of cell lines. Furthermore, TAK1 inhibition causes G2-M cell-cycle blockade and polyploidy in many of the cell lines. MEK plus TAK1 inhibition causes reduced G2-M/polyploid cell numbers and additive cytotoxic effects in KRAS/TAK1-dependent cell lines as well as a subset of BRAF-mutant cells. Mechanistically, sensitivity to MEK/TAK1 inhibition can be conferred by KRAS and BMP receptor activation, which promote expression of NF kappaB-dependent proinflammatory cytokines, driving tumor cell survival and proliferation. MEK/TAK1 inhibition causes reduced mTOR, Wnt, and NF-kappaB signaling in TAK1/MEK-dependent cell lines concomitant with apoptosis. A Wnt/NF kappaB transcriptional signature was derived that stratifies primary tumors into three major subtypes: Wnt-high/NF-kappaB-low, Wnt-low/NF-kappaB-high and Wnt high/NF-kappaB-high, designated W, N, and WN, respectively. These subtypes have distinct characteristics, including enrichment for BRAF mutations with serrated carcinoma histology in the N subtype. Both N and WN subtypes bear molecular hallmarks of MEK and TAK1 dependency seen in cell lines. Therefore, N and WN subtype signatures could be utilized to identify tumors that are most sensitive to anti-MEK/TAK1 therapeutics. IMPLICATIONS: This study describes a potential therapeutic strategy for a subset of colon cancers that are dependent on oncogenic KRAS signaling pathways, which are currently difficult to block with selective agents. Mol Cancer Res; 14(12); 1204-16. (c)2016 AACR. PMID- 27655130 TI - Oncofetal Chondroitin Sulfate Glycosaminoglycans Are Key Players in Integrin Signaling and Tumor Cell Motility. AB - : Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from the malaria parasite, Plasmodium falciparum We demonstrate that ofCS plays a key role in tumor cell motility by affecting canonical integrin signaling pathways. Binding of rVAR2 to tumor cells inhibited the interaction of cells with extracellular matrix (ECM) components, which correlated with decreased phosphorylation of Src kinase. Moreover, rVAR2 binding decreased migration, invasion, and anchorage-independent growth of tumor cells in vitro Mass spectrometry of ofCS-modified proteoglycan complexes affinity purified from tumor cell lines on rVAR2 columns revealed an overrepresentation of proteins involved in cell motility and integrin signaling, such as integrin-beta1 (ITGB1) and integrin-alpha4 (ITGA4). Saturating concentrations of rVAR2 inhibited downstream integrin signaling, which was mimicked by knockdown of the core chondroitin sulfate synthesis enzymes beta-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1). The ofCS modification was highly expressed in both human and murine metastatic lesions in situ and preincubation or early intravenous treatment of tumor cells with rVAR2 inhibited seeding and spreading of tumor cells in mice. This was associated with a significant increase in survival of the animals. These data functionally link ofCS modifications with cancer cell motility and further highlights ofCS as a novel therapeutic cancer target. IMPLICATIONS: The cancer-specific expression of ofCS aids in metastatic phenotypes and is a candidate target for therapy. Mol Cancer Res; 14(12); 1288-99. (c)2016 AACR. PMID- 27655132 TI - Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus. AB - BACKGROUND: The association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population. METHODS: Experts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership (UKAP; www.UKADHD.com ) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD. RESULTS: The authors successfully came to consensus and produced recommended guidelines with specific regards to identification and assessment, interventions and treatments, and multiagency liaisons and care management, highlighting that a lifespan approach to treatment needs to be adopted by all involved. Included in the guidelines are: 1) unique 'red flags', which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management. CONCLUSIONS: While clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD. PMID- 27655133 TI - Species diversity and spatial distribution of ixodid ticks on small ruminants in Greece. AB - A cross sectional field study on the distribution of Ixodidae ticks was carried out over two consecutive tick seasons (2012 and 2013) in small ruminants (309 farms) located in mainland and five islands of Greece. A total of 2108 ticks (1199 females, 908 males, and 1 nymph) were collected from sheep and goats. Two species of Rhipicephalus, two of Ixodes, five of Hyalomma, three of Haemaphysalis, and one of Dermacentor were detected. The species with the widest distribution were Rhipicephalus sanguineus s.l. (64.8 %), R. bursa (25.9 %), and Dermacentor marginatus (4.1 %), whereas the least frequently collected species were Ixodes ricinus, I. gibbosus, Haemaphysalis parva, H. sulcata, H. punctata, Hyalomma marginatum, H. excavatum, H. dromedarii, H. rufipes, and H. impeltatum representing together less than 5.3 % of the collections. R. sanguineus s.l. was the predominant species, while D. marginatus and I. gibbosus were restricted to the northeastern Aegean Sea islands. This is the first survey on tick fauna from mainland and islands in Greece. PMID- 27655131 TI - The Cytoskeletal Adapter Protein Spinophilin Regulates Invadopodia Dynamics and Tumor Cell Invasion in Glioblastoma. AB - : Glioblastoma is a primary brain cancer that is resistant to all treatment modalities. This resistance is due, in large part, to invasive cancer cells that disperse from the main tumor site, escape surgical resection, and contribute to recurrent secondary lesions. The adhesion and signaling mechanisms that drive glioblastoma cell invasion remain enigmatic, and as a result there are no effective anti-invasive clinical therapies. Here we have characterized a novel adhesion and signaling pathway comprised of the integrin alphavbeta8 and its intracellular binding partner, Spinophilin (Spn), which regulates glioblastoma cell invasion in the brain microenvironment. We show for the first time that Spn binds directly to the cytoplasmic domain of beta8 integrin in glioblastoma cells. Genetically targeting Spn leads to enhanced invasive cell growth in preclinical models of glioblastoma. Spn regulates glioblastoma cell invasion by modulating the formation and dissolution of invadopodia. Spn-regulated invadopodia dynamics are dependent, in part, on proper spatiotemporal activation of the Rac1 GTPase. Glioblastoma cells that lack Spn showed diminished Rac1 activities, increased numbers of invadopodia, and enhanced extracellular matrix degradation. Collectively, these data identify Spn as a critical adhesion and signaling protein that is essential for modulating glioblastoma cell invasion in the brain microenvironment. IMPLICATIONS: Tumor cell invasion is a major clinical obstacle in glioblastoma and this study identifies a new signaling pathway regulated by Spinophilin in invasive glioblastoma. Mol Cancer Res; 14(12); 1277-87. (c)2016 AACR. PMID- 27655136 TI - Design Expert((r)) supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson's disease. AB - Selegiline is a monoamine oxidase B (MAO-B) inhibitor and is used in the treatment of Parkinson's disease. The main problem associated with its oral administration is its low oral bioavailability (10%) due to its poor aqueous solubility and extensive first pass metabolism. The aim of the present research work was to develop a nanoemulsion loaded with selegiline for direct nose-to brain delivery for the better management of Parkinson's disease. A quality by design (QbD) approach was used in a statistical multivariate method for the preparation and optimization of nanoemulsion. In this study, four independent variables were chosen, in which two were compositions and two were process variables, while droplet size, transmittance, zeta potential and drug release were selected as response variables. The optimized formulation was assessed for efficacy in Parkinson's disease using behavioural studies, namely forced swimming, locomotor, catalepsy, muscle coordination, akinesia and bradykinesia or pole test in Wistar rats. The observed droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential and viscosity of selegiline nanoemulsion were found to be 61.43 +/- 4.10 nm, 0.203 +/- 0.005, 1.30 +/- 0.01, 99.80 +/- 0.04%, -34 mV and 31.85 +/- 0.24 mPas respectively. Surface characterization studies demonstrated a spherical shape of nanoemulsion which showed 3.7 times enhancement in drug permeation as compared to drug suspension. The results of behaviour studies showed that treatment of haloperidol induced Parkinson's disease in rats with selegiline nanoemulsion (administered intranasally) showed significant improvement in behavioural activities in comparison to orally administered drug. These findings demonstrate that nanoemulsion could be a promising new drug delivery carrier for intranasal delivery of selegiline in the treatment of Parkinson's disease. PMID- 27655134 TI - Hepatitis C virus replicative double-stranded RNA is a potent interferon inducer that triggers interferon production through MDA5. AB - The cytoplasmic RNA sensors, retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, play crucial roles in innate sensing of hepatitis C virus (HCV). However, the exact identity of the IFN inducer generated during HCV infection is poorly understood. To identify the IFN inducer, we extracted the RNAs from HCV-replicating cells and introduced these into IFN signalling-competent cells to examine IFN production. RNAs isolated from HCV replicating cells triggered robust IFN-beta and IFN-lambda production in Huh7 cells in a viral replication-dependent manner, preferentially through the melanoma differentiation-associated gene 5 but not through the retinoic acid inducible gene I-mediated pathway. The IFN-inducing capacity of HCV RNA survived after calf intestinal alkaline phosphatase and ssRNA-specific S1 nuclease treatment, but was completely eliminated by dsRNA-specific RNase III digestion, suggesting that viral replicative dsRNA is an IFN inducer. Furthermore, HCV viral RNA extracted from replicating cells was sensitive to 5'-monophosphate-dependent 5'->3' exonuclease (TER) digestion, suggesting that the HCV genome lacks a 5' triphosphate or -diphosphate. In semi-permeabilized cells, the HCV IFN inducer primarily resided in an enclosed membranous structure that protects the IFN inducer from RNase digestion. Taken together, we identified HCV replicative dsRNA as a viral IFN inducer enclosed within the viral replication factory. PMID- 27655135 TI - Choosing wisely and preoperative hemoglobin A1c testing: what should it mean? PMID- 27655138 TI - Advances in molecular genetics for pulmonary atresia. AB - Genetic and environmental factors may be similar in certain CHD. It has been widely accepted that it is the cumulative effect of these risk factors that results in disease. Pulmonary atresia is a rare type of complex cyanotic CHD with a poor prognosis. Understanding the molecular mechanism of pulmonary atresia is essential for future diagnosis, prevention, and therapeutic approaches. In this article, we reviewed several related copy number variants and related genetic mutations, which were identified in patients with pulmonary atresia, including pulmonary atresia with ventricular septal defect and pulmonary atresia with intact ventricular septum. PMID- 27655137 TI - The Mouse-Specific Splice Variant mRAGE_v4 Encodes a Membrane-Bound RAGE That Is Resistant to Shedding and Does Not Contribute to the Production of Soluble RAGE. AB - The receptor for advanced glycation end-products (RAGE) is involved in the onset and progression of several inflammatory diseases. The RAGE primary transcript undergoes numerous alternative splicing (AS) events, some of which are species specific. Here, we characterize the mouse-specific mRAGE_v4 splice variant, which is conserved in rodents and absent in primates. mRAGE_v4 derives from exon 9 skipping and encodes a receptor (M-RAGE) that lacks 9 amino acids between the transmembrane and the immunoglobulin (Ig) domains. RNA-Seq data confirm that in mouse lung mRAGE_v4 is the most abundant RAGE mRNA isoform after mRAGE, which codes for full-length RAGE (FL-RAGE), while in heart all RAGE variants are almost undetectable. The proteins M-RAGE and FL-RAGE are roughly equally abundant in mouse lung. Contrary to FL-RAGE, M-RAGE is extremely resistant to shedding because it lacks the peptide motif recognized by both ADAM10 and MMP9, and does not contribute significantly to soluble cRAGE formation. Thus, a cassette exon in RAGE corresponds to a specific function of the RAGE protein-the ability to be shed. Given the differences in RAGE AS variants between rodents and humans, caution is due in the interpretation of results obtained in mouse models of RAGE dependent human pathologies. PMID- 27655139 TI - Overview of Total Knee Arthroplasty and Modern Pain Control Strategies. AB - Perioperative pain management of total knee arthroplasty (TKA) remains a challenge for physicians and anesthesiologists. Reducing postoperative pain is an essential component of patient satisfaction, functional outcomes, and hospital length of stay. Multimodal pain management regimens have been demonstrated to be superior to monotherapy in achieving adequate pain control, as well as an effective method of limiting side effects of analgesics. In the present investigation, we present literature published over the last year relating to new advancements in perioperative pain management for TKA. While it is widely accepted that methods including peripheral nerve blocks and local anesthetic injections are essential to pain protocols, there is still conflicting evidence over what modalities provide superior relief. The incorporation of cryoneurolysis preoperatively is a new modality which has been incorporated and has been shown to improve pain control in patients undergoing TKA. PMID- 27655140 TI - Predictor characteristics necessary for building a clinically useful risk prediction model: a simulation study. AB - BACKGROUND: Compelled by the intuitive appeal of predicting each individual patient's risk of an outcome, there is a growing interest in risk prediction models. While the statistical methods used to build prediction models are increasingly well understood, the literature offers little insight to researchers seeking to gauge a priori whether a prediction model is likely to perform well for their particular research question. The objective of this study was to inform the development of new risk prediction models by evaluating model performance under a wide range of predictor characteristics. METHODS: Data from all births to overweight or obese women in British Columbia, Canada from 2004 to 2012 (n = 75,225) were used to build a risk prediction model for preeclampsia. The data were then augmented with simulated predictors of the outcome with pre-set prevalence values and univariable odds ratios. We built 120 risk prediction models that included known demographic and clinical predictors, and one, three, or five of the simulated variables. Finally, we evaluated standard model performance criteria (discrimination, risk stratification capacity, calibration, and Nagelkerke's r2) for each model. RESULTS: Findings from our models built with simulated predictors demonstrated the predictor characteristics required for a risk prediction model to adequately discriminate cases from non-cases and to adequately classify patients into clinically distinct risk groups. Several predictor characteristics can yield well performing risk prediction models; however, these characteristics are not typical of predictor-outcome relationships in many population-based or clinical data sets. Novel predictors must be both strongly associated with the outcome and prevalent in the population to be useful for clinical prediction modeling (e.g., one predictor with prevalence >=20 % and odds ratio >=8, or 3 predictors with prevalence >=10 % and odds ratios >=4). Area under the receiver operating characteristic curve values of >0.8 were necessary to achieve reasonable risk stratification capacity. CONCLUSIONS: Our findings provide a guide for researchers to estimate the expected performance of a prediction model before a model has been built based on the characteristics of available predictors. PMID- 27655141 TI - How to assess femoral and tibial component rotation after total knee arthroplasty with computed tomography: a systematic review. AB - PURPOSE: One of the most important factors leading to revision of total knee arthroplasties (TKA) is malrotation of femoral and/or tibial component. Rotation measurements performed on radiographs are limited and less reliable compared to 2D computed tomography (CT). Nowadays, 2D-CT and 3D-CT can be distinguished in measuring rotation of the TKA components. The aim of this systematic review is to determine the most reliable CT techniques in measuring rotation of the TKA components and to investigate possible cut-off points that can be used in the clinician's decision for a possible revision of the TKA. METHODS: A search of PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science was performed up to April 2015. Final selections of 12 articles were used in this systematic review. RESULTS: 3D-CT, compared to 2D-CT, is more reliable and shows a high level of intra- and interobserver reliability. Femoral component rotation is measured using the component's posterior condylar line or inner pegs in relation to the epicondylar axis. Five different techniques were used to measure tibial component rotation. The posterior border of the tibial component in relationship to the geometric centre and tibial tubercle was most frequently used. CONCLUSION: This systematic review shows a strong preference for 3D-CT to determine the component's rotation following a TKA. The literature shows consensus on the reference points of the femoral component. In measurements of the tibial component, various techniques are used with similar results. No clear cut-off point for revision of malrotated TKA components can be stated because of limited evidence. LEVEL OF EVIDENCE: III. PMID- 27655142 TI - Prolonged persistence of a novel replication-defective HIV-1 variant in plasma of a patient on suppressive therapy. AB - BACKGROUND: Cell-free residual HIV-1 virions (RVs) persist in plasma below 20-50 vRNA copies/ml in most patients on suppressive antiretroviral therapy (ART). How RVs are produced in the body during therapy is not fully clear. In this study, we have attempted to characterize these viruses of an ART-treated patient in vitro in order to gain insights into the mechanism of their production in vivo. METHODS: We have reconstructed almost the entire genomes of RVs as DNA forms using the patient's residual plasma vRNA by an overlapping RT-nested PCR method, and then sequence-analyzed the cloned genomes and tested them for their biological activities in vitro. RESULTS: We found that the reconstructed molecular clones of RVs lacked antiretroviral drug-resistant mutations, as well as G-to-A hypermutations. The vDNA clones, when transfected into TZM-bl cells, released HIV-p24 into the culture media at extremely low levels. This low-level virus production was found to be due to the presence of a unique mutation (GU-to GC) in the conserved 5'-major splice donor (MSD) motif of the corresponding vRNAs. We found that the incorporation of this point mutation by itself could cause defects in the replication of a standard HIV strain (JRCSF) in vitro. However, this novel viral variant was intermittently detected at 5 of 7 time points in the patient's plasma over a period of 39 months during therapy. CONCLUSIONS: This is the first identification of a natural point mutation (GU-to GC) in the conserved 5'-MSD motif of HIV genomic RNA. The intermittent but prolonged detection of this replication-defective HIV variant in the patient's plasma among other viral populations strongly suggests that this variant is released from highly stable productively infected cells present in vivo during therapy. The potential implication of this observation is that the elimination of such productively infected cells that contribute to residual viremia during suppressive therapy could be an important first step towards achieving a cure for HIV. PMID- 27655143 TI - Sluggish Cognitive Tempo and Speed of Performance. AB - OBJECTIVE: This study examined whether college students who reported higher levels of sluggish cognitive tempo (SCT) symptoms were actually more "sluggish" in their performance while completing speeded cognitive and academic measures. METHOD: College students ( N = 253) completed self-reports of SCT and their reading and test-taking abilities as well as tests of processing speed, reading fluency, and reading comprehension. RESULTS: Across all variables, SCT symptoms were most significantly associated with self-reported difficulty on timed reading tasks. However, students with high SCT scores were not significantly slower than controls on any of the timed tasks. CONCLUSION: In college students, self-reports of high SCT levels do not suggest actual slow performance on cognitive and academic tasks. PMID- 27655144 TI - The Clinical Characteristics of ADHD and Obsessive-Compulsive Disorder Comorbidity. AB - OBJECTIVE: To investigate the clinical implications of obsessive-compulsive disorder (OCD) and ADHD comorbidity in adults. METHOD: The OCD patients who had and had no diagnosis of adulthood ADHD were compared in terms of several demographic and clinical variables. RESULTS: The mean number of obsessions and compulsions; hoarding, symmetry, and miscellaneous obsessions; ordering/arranging and hoarding compulsions; total, attentional, and motor subscale scores of Barratt Impulsivity Scale (BIS)-11 were more frequent among the patients with OCD ADHD. The mean age of onset was more likely to be earlier in ADHD-OCD group than in OCD group. Impulsivity, symmetry obsessions, and hoarding compulsions strongly predicted the coexistence between ADHD and OCD. CONCLUSION: OCD-ADHD comorbidity in adults seemed to be associated with an earlier onset of OCD, with the predominance of impulsivity, and with a different obsessive-compulsive symptom (OC) profile from OCD patients without a diagnosis of ADHD. PMID- 27655145 TI - Histopatholological Findings in a Fatal Case of Rinkhals Envenomation: A New Forensic Pathology Finding? AB - Although cobra envenomation continues to pose a threat to life and therefore constitutes a major cause of death in Africa, India, and Sri Lanka, the forensic pathology reports are not always histologically well documented or illustrated. The reports in the literature, although providing graphic evidence of the macroscopic appearances of the bite and its ensuing tissue necrosis, should the victim survive, often do not illustrate the histopathological findings to a sufficient degree. We present an unusual case of fatal envenomation by a rinkhals (Hemachatus haemachatus) in which the victim had been bitten a second time after a previous rinkhals' bite. Two issues therefore arose: (a) whether the histopathological findings in the spleen were an acute reaction to the snake bite or were due to immunostimulation as a consequence of the previously inflicted bite, and (b) the previously undocumented finding of extravasation of erythrocytes into the surrounding Virchow-Robin spaces in the brain, a finding usually associated with blunt head trauma and therefore interpreted as a cortical contusion hemorrhage by forensic pathologists. PMID- 27655146 TI - Towards an electroretinographic assay for studying colour vision in human observers. AB - PURPOSE: To determine whether electroretinograms (ERGs) to heterochromatic stimulation can detect and quantify hereditary colour vision deficiency. METHODS: ERGs were measured to counterphase modulation of red and green stimuli. The total modulation depth of the red and green stimuli was constant. The ratio of red to green modulation was varied, and the responses were measured at two temporal frequencies: 12 and 36 Hz. Subjects were 13 protanopes, 19 protanomalous trichromats, 38 deuteranopes, 16 deuteranomalous trichromats and 22 normal trichromats. RESULTS: The responses are in agreement with previous findings: they were determined by a vector additive input of L- and M-cones (and thus is luminance sensitive) at 36 Hz. At 12 Hz, the responses can be modelled a vector addition of an L-/M-additive response (as determined by the 36 Hz ERGs) and an L /M-opponent response. From the models, L-cone input fraction (36 Hz) and luminance input fraction (12 Hz) were estimated. The five groups showed different characteristics. However, the signal-to-noise ratio (SNR) at 12 Hz was not always satisfactory. CONCLUSIONS: The ERGs to heterochromatic stimuli are potentially interesting for determining the presence and the type of colour vision deficiencies, provided some measures are taken to improve the 12 Hz SNRs. PMID- 27655147 TI - A late foveal response component of multifocal electroretinograms in healthy subjects. AB - PURPOSE: To investigate the characteristics of the late foveal response component (lfrc) that presents on the first slice of the second-order kernel (K2.1) in multifocal electroretinograms (mfERGs). METHODS: mfERGs with 37 hexagonal stimulus elements were obtained from 27 healthy subjects under a stimulus intensity of 2.67 cds/m2, base rate of 75 Hz, and a net recording time of 1 min 49.2 s, using bipolar contact lens electrodes. The responses on the centermost hexagon (with a diameter of 4.5 degrees -5.2 degrees ) were designated as foveal mfERGs. RESULTS: The foveal mfERG of the first-order kernel (K1) was shaped similarly to the K1 of the surrounding mfERGs. The foveal mfERG of K2.1 differed from the K2.1s of the surrounding mfERGs. This difference varied among subjects; however, the potential (0.34 +/- 0.10 uV: mean +/- SD) of the lfrc acutely changed at approximately 50 ms (range 48.56 +/- 1.02-56.86 +/- 1.99 ms). Whereas the amplitudes of the other major components of K1 and K2.1 significantly decreased with increasing refractive error, the amplitude of lfrc was not significantly correlated with refraction in this cohort. CONCLUSIONS: The lfrc was obtained only on the centermost hexagon within an appropriate recording time (<2 min). This finding reflects the particular structure and peculiar adaptiveness of the fovea, a specialized area of the human retina, and enables the estimation of foveal function in clinical practice. PMID- 27655149 TI - An anatomical study of the intersigmoid fossa and applications for internal hernia surgery. AB - PURPOSE: To improve the knowledge of the morphometry and the surrounding anatomical structures of the intersigmoid fossa and to determine possible surgical applications. METHOD: Forty eight adult cadavers (29 female and 19 male; mean age 83 years) underwent dissection in the Laboratoire d'Anatomie des Alpes Francaises. Two injections in the right carotid resulted in a total body concentration of formalin of 1.3 %. The study parameters were the dimensions of the intersigmoid fossa orifice and the fossa's relationship to surrounding structures. Data were recorded and analyzed using Microsoft Office Excel (MS Cerp). A Pearson coefficient r was used to examine the correlation between the length of colon and the ISF volume. RESULTS: The intersigmoid fossa was present in 75 % of cases (n = 36). The average dimensions for the transverse diameter, longitudinal diameter, and the depth were, respectively, 20.5 +/- 0.2, 20.3 +/- 0.13, and 26.8 +/- 0.2 mm. The primary and secondary roots bordering this fossa measured on average 59.1 +/- 0.1 and 48.3 +/- 0.13 mm. In 13.9 % of cases (n = 5), the maximum depth was >40 mm and in 16.7 % of cases (n = 6), one of the diameters of the orifice entry of the fossa was >40 mm. The ureter and external iliac artery were the most frequently encountered structures during the dissection of the fundus of the intersigmoid fossa. CONCLUSION: The intersigmoid fossa remains present in most of the reported dissections of cadavers. It constitutes an essential landmark in the surgery of the sigmoid colon due to its deep structural relationship with the left ureter and external iliac artery. PMID- 27655148 TI - Vascular anatomy of the stomach related to resection procedures strategy. AB - This study is focused on the vascular anatomy of the stomach in relation to the gastric pull-up construction. The vascular anatomy was studied on forty-one human specimens. We find out the differences in blood supplement between anterior and posterior wall. It was maked an review of the main trunk arteries of the stomach. To display the vessels of the stomach we used diaphanoscopy, digital shooting in special mode and micro preparation of the vessels. We find out that left gastric artery gives more branches to the posterior wall and right gastroepiploic artery (RGEA) gives more branches to the anterior wall. But brunches of RGEA are longer on the posterior wall than on the anterior. Also we are offering the new classification of the RGEA related to gastric pull-up construction. This classification based not only on the anatomical shapes of RGEA but on the properties of the flow dynamics through the artery. PMID- 27655150 TI - Functionalized magnetic microparticle-based colorimetric platform for influenza A virus detection. AB - A colorimetric platform for influenza A virus detection was developed by using the high efficiency of enzymatic catalysis and the reduction of gold ions with hydrogen peroxide. Aptamer-functionalized magnetic microparticles were synthesized to capture the influenza A virus. This was followed by the binding of ConA-GOx-AuNPs to the H3N2 virus through the ConA-glycan interaction. The sandwich complex was subsequently dispersed in glucose solution to trigger an enzymatic reaction to produce hydrogen peroxide, which controlled the growth of gold nanoparticles and produced colored solutions. The determination of H3N2 concentration was realized by comparing the two differently colored gold nanoparticles. This method could detect the target virus as low as 11.16 MUg ml( 1). Furthermore, it opens new opportunities for sensitive and colorimetric detection of viruses and proteins. PMID- 27655151 TI - Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. AB - High frequency of gastrointestinal yeast presence in ASD subjects was shown through a simple cultural approach (Candida spp. in 57.5 % of ASDs and no controls); the identification of aggressive form (pseudo-hyphae presenting) of Candida spp. at light microscope means that adhesion to intestinal mucosa is facilitated. Dysbiosis appears sustained by lowered Lactobacillus spp. and decreased number of Clostridium spp. Absence of C. difficilis and its toxins in both ASDs and controls is also shown. Low-mild gut inflammation and augmented intestinal permeability were demonstrated together with the presence of GI symptoms. Significant linear correlation was found between disease severity (CARs score) and calprotectin and Clostridium spp. presence. Also GI symptoms, such as constipation and alternating bowel, did correlate (multivariate analyses) with the increased permeability to lactulose. The present data provide rationale basis to a possible specific therapeutic intervention in restoring gut homeostasis in ASDs. PMID- 27655153 TI - Observations on obesity patterns in tetralogy of Fallot patients from childhood to adulthood. AB - Obesity is increasingly prevalent, and abnormal body mass index is a risk factor for cardiovascular disease. There are limited data published regarding body mass index and CHD. We tested the hypothesis that body mass index and obesity prevalence are increasing in patients with tetralogy of Fallot over time by analysing time since surgery, age, height, weight, and body mass index among tetralogy of Fallot patients and demographic data from age-matched controls. NYHA class and left ventricular ejection fraction were analysed in adults. Body mass index was categorised into normal, overweight, and obese in this single-centre, retrospective chart review. Data were collected from 137 tetralogy of Fallot patients (71 men:66 women), of whom 40 had body mass index >25 kg/m2. Tetralogy of Fallot patients aged <6 years had lower body mass index (15.9 versus 17.1; p=0.042) until 16-20 years of age (27.4 versus 25.4; p=0.43). For adult tetralogy of Fallot patients, the mean body mass index was 26.5 but not statistically significantly different from the control cohort. Obese adult patients had significantly higher average NYHA class compared with those of normal weight (p=0.03), but no differences in left ventricular ejection fraction by echocardiography (p=0.55) or cardiac MRI (p=0.26) were noted. Lower body mass index was observed initially in tetralogy of Fallot patients, but by late adolescence no significant difference was observed. As adults, tetralogy of Fallot patients with higher body mass index had increased NYHA class but similar left ventricular ejection fraction. PMID- 27655152 TI - Equine Pulmonary Cryptococcosis: A Comparative Literature Review and Evaluation of Fluconazole Monotherapy. AB - Cryptococcus is the most common fungal respiratory pathogen in Australian horses, manifesting primarily as pulmonary granulomas. Disease severity at presentation is dependent on the athletic use of the horse. The diagnosis and estimation of disease severity are centred around clinical findings, cytological evaluation of respiratory tract secretions, diagnostic imaging, and antigen titre testing. Both the lateral flow assay and the latex cryptococcal antigen titre are used, and important similarities and differences between species are discussed. Cryptococcus gattii occurs with greater frequency than Cryptococcus neoformans in equine pulmonic cryptococcosis and can be successfully treated with enteral fluconazole monotherapy, with disease severity determining treatment length. PMID- 27655154 TI - Impairment of Small Intestinal Function in Ulcerative Colitis: Role of Enteric Innervation. AB - Small intestinal dysfunction has been described in patients with ulcerative colitis and in experimental animal models of colitis. This is demonstrated by a decrease in fluid, electrolyte, amino acid, fat and carbohydrate absorption as well as by deranged intestinal motility. Histopathological changes in the small intestines in colitis have not been consistently demonstrated, but there is evidence of structural and biochemical alterations as shown by increased intestinal permeability and a decrease in the expression of multiple brush border membrane enzymes such as disaccharidases and aminopetidases, in both humans and experimental animals. The pathophysiology of this dysfunction has not been elucidated, but it is thought to include alterations in neural circuitry such as increased neuronal excitability, neuronal damage and changes of neuropeptidergic innervation and receptors as well as an increase in local production of pro inflammatory cytokines and alterations in the production of some neurohumoral mediators. In the following, we provide an update on the advancement of clinical and scientific contributions to elucidate the underlying mechanisms of the alteration of the functions of apparently intact small intestinal segments, induced by ulcerative colitis. PMID- 27655155 TI - Structure of the catalytic domain of the colistin resistance enzyme MCR-1. AB - BACKGROUND: Due to the paucity of novel antibiotics, colistin has become a last resort antibiotic for treating multidrug resistant bacteria. Colistin acts by binding the lipid A component of lipopolysaccharides and subsequently disrupting the bacterial membrane. The recently identified plasmid-encoded MCR-1 enzyme is the first transmissible colistin resistance determinant and is a cause for concern for the spread of this resistance trait. MCR-1 is a phosphoethanolamine transferase that catalyzes the addition of phosphoethanolamine to lipid A to decrease colistin affinity. RESULTS: The structure of the catalytic domain of MCR 1 at 1.32 A reveals the active site is similar to that of related phosphoethanolamine transferases. CONCLUSIONS: The putative nucleophile for catalysis, threonine 285, is phosphorylated in cMCR-1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. As noted for catalytic domains of other phosphoethanolamine transferases, binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the cMCR-1 structure, suggesting that they are present in the membrane domain. PMID- 27655158 TI - CE: A Review of Common Oral Treatments for Breast Cancer: Improving Patient Safety in Nononcology Settings. AB - : Breast cancer patients are living longer with the disease than ever before. According to the National Cancer Institute, more than 3 million women in the United States are currently living with a breast cancer diagnosis, and many seek care in nononcology settings, whether for treatment, acute symptoms and complaints related to their cancer diagnosis, or unrelated concerns. Yet many nononcology providers are unfamiliar with the various oral agents used to treat breast cancer, and their possible adverse effects and drug interactions. It is imperative that all providers be aware of these agents and know when a patient is currently taking or has taken them. This article provides an overview of the most common oral treatments for breast cancer and discusses common adverse effects and management. PMID- 27655157 TI - Cognitive profiles in degenerative dementia without evidence of small vessel pathology and small vessel vascular dementia. AB - Although a large number of studies have examined possible differences in cognitive performance between Alzheimer's disease (AD) and vascular dementia (VaD), the data in the literature are conflicting. The aims of this study were to analyze the neuropsychological pattern of subjects affected by degenerative dementia without evidence of small vessel pathology (DD) and small vessel VaD subjects in the early stages and to investigate differences in the progression of cognitive impairment. Seventy-five patients with probable VaD and 75 patients with probable DD were included. All the subjects underwent a standard neuropsychological evaluation, including the following test: Visual Search, Attentional matrices, Story Recall, Raven's Coloured Progressive Matrices, Phonological and Semantic Verbal Fluency, Token, and Copying Drawings. The severity of cognitive impairment was stratified according to the MMSE score. Fifteen subjects with probable DD and 10 subjects with probable VaD underwent a 12-month cognitive re-evaluation. No significant difference was found between DD and VaD subjects in any of the neuropsychological tests except Story Recall in the mild cognitive impairment (P < 0.001). The re-test value was significantly worse than the baseline value in the MMSE (P = 0.037), Corsi (P = 0.041), Story Recall (P = 0.032), Phonological Verbal Fluency (P = 0.02), and Copying Drawings (P = 0.043) in DD patients and in the Visual Search test (P = 0.036) in VaD subjects. These results suggest that a neuropsychological evaluation might help to differentiate degenerative dementia without evidence of small vessel pathology from small vessel VaD in the early stages of these diseases. PMID- 27655156 TI - Subsocial Cockroaches Nauphoeta cinerea Mate Indiscriminately with Kin Despite High Costs of Inbreeding. AB - Many animals have evolved strategies to reduce risks of inbreeding and its deleterious effects on the progeny. In social arthropods, such as the eusocial ants and bees, inbreeding avoidance is typically achieved by the dispersal of breeders from their native colony. However studies in presocial insects suggest that kin discrimination during mate choice may be a more common mechanism in socially simpler species with no reproductive division of labour. Here we examined this possibility in the subsocial cockroach Nauphoeta cinerea, a model species for research in sexual selection, where males establish dominance hierarchies to access females and control breeding territories. When given a binary choice between a sibling male and a non-sibling male that had the opportunity to establish a hierarchy prior to the tests, females mated preferentially with the dominant male, irrespective of kinship or body size. Despite the lack of kin discrimination during mate choice, inbred-mated females incurred significant fitness costs, producing 20% less offspring than outbred mated females. We discuss how the social mating system of this territorial cockroach may naturally limit the probability of siblings to encounter and reproduce, without the need for evolving active inbreeding avoidance mechanisms, such as kin recognition. PMID- 27655159 TI - CE: Assessing and Managing Pain, Agitation, and Delirium in Hospitalized Older Adults. AB - : In the acute care setting, pain, agitation, and delirium (PAD) often occur as interrelated parts of a syndrome rather than as separate entities. Because the three facets of PAD may be similar in presentation, it is often difficult for clinicians to recognize the syndrome and to assess and treat it. The challenge is particularly great in older patients, who are more likely than their younger counterparts to have such comorbid conditions as dementia, which may impair the ability to report pain, or age-related physiologic changes that may affect the metabolism and clearance of certain medications. This article provides an overview of each aspect of PAD, discusses clinical considerations related to the assessment and treatment of the syndrome in older adults receiving acute care, and illustrates the application of published PAD guidelines through the use of a hypothetical patient scenario. PMID- 27655161 TI - Evaluation of the Tekscan F-SCAN system for measurement of the kicking force in horses. AB - INTRODUCTION: The incidence of fractures after a kick, coupled with marked soft tissue trauma at the site of injury, suggests that the force of a kick from the hind limb of a horse is enormous. The goal of this study was to measure this force and to investigate whether the Tekscan F-SCAN in-shoe pressure measuring system is suitable for quantification of the impact strength of a kick from a horse. The system was tested in 6 horses that had undergone clinical examination and gait analysis. The sensor-shoe combination was attached to each hind foot and the horse was stimulated to kick against a wall. The F-SCAN system measured the maximum vertical and horizontal force (N), the main contact area (cm2) of the sole with the floor (stance phase limb) or wall (kicking limb) and the duration (sec) that the sole was in contact with the floor or wall. In addition, each kicking event was recorded with a video camera for subjective evaluation. The mean kicking force measured was lower than that recorded in horses trotting on a treadmill, where the forces exerted on one limb were similar to the horse's body weight. The results of this study indicate that the Tekscan F-SCAN system is not ideally suited to measure the force of a kick of a horse in vivo. PMID- 27655160 TI - Treatment of cows with parturient paresis using intravenous calcium and oral sodium phosphate. AB - INTRODUCTION: The goal of this study was to investigate whether intravenous infusion of 1000 ml 40% calcium borogluconate combined with the oral adminstration of 500 g sodium phosphate leads to a better cure rate and longer lasting normocalcaemia and normophosphataemia than standard intravenous treatment with 500 ml calcium borogluconate in cows with parturient paresis. Forty recumbent cows with hypocalcaemia and hypophosphataemia were alternately allocated to group A or B. Cows of both groups were treated intravenously with 500 ml 40% calcium borogluconate, and cows of group B additionally received another 500 ml calcium borogluconate via slow intravenous infusion and 500 g sodium phosphate administered via an orogastric tube. Thirty-two cows stood within 8 hours after the start of treatment and 8 did not; of the 32 cows that stood, 18 belonged to group A and 14 to group B (90% of group A vs. 70% of group B; P = 0.23). Seven cows relapsed; of these and the 8 that did not respond to initial treatment, 10 stood after two standard intravenous treatments. Downer cow syndrome occurred in 5 cows, 3 of which recovered after aggressive therapy. The overall cure rate did not differ significantly between groups A and B. Twelve (60%) cows of group A and 14 (70%) cows of group B were cured after a single treatment and of the remaining 14, 11 were cured after two or more treatments. Two downer cows were euthanized and one other died of heart failure during treatment. Serum calcium concentrations during the first eight hours after the start of treatment were significantly higher in group B than in group A, and oral sodium phosphate caused a significant and lasting increase in inorganic phosphate. More cows of group B than group A were cured after a single treatment (P > 0.05). These findings, although not statistically significant, are promising and should be verified using a larger number of cows. PMID- 27655162 TI - Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment. AB - INTRODUCTION: Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased. PMID- 27655163 TI - [Veterinary care of birds of prey: Development from 1985 to 2015]. AB - INTRODUCTION: A retrospective study was conducted which analysed the patient histories of free-living birds of prey presented to the Clinic of Zoo Animals, Exotic Pets and Wildlife of the University of Zurich from 2009 to 2015. The data were compared with a previous study on the period from 1985 to 1994. The average number of cases presented per year increased from 55 to 109. Most cases are presented in the months of February, June and July. Surgical problems were most frequently diagnosed and occurred in 61.5% of the cases, with 66.5% of patients presenting with one or more fractures. Regarding medical cases (29.5%) the most frequent finding was unspecified weakness (47.8%). Ophthalmic pathologies were diagnosed in 9% of the patients. With respect to outcome 41.7% of the patients could be released, 47.3% and 11.0% had to be euthanized or died, respectively. In 6 of 9 of the most frequently presented species the rate of release increased significantly compared to the previous study. PMID- 27655164 TI - [Intralymphatic immunotherapy: An effective and safe alternative route for canine atopic dermatitis]. AB - INTRODUCTION: Allergen-specific immunotherapy (ASIT) is the only etiologic treatment of atopic dermatitis in dogs. In humans it has been shown that intralymphatic immunotherapy (ILIT) enhanced efficacy and patient compliance and reduced treatment time from 3 years to 8 weeks. As only safety data have been published yet, the aim of this study was to evaluate the clinical efficacy of ILIT in dogs. 20 atopic dogs underwent ILIT with alum-precipitated allergens administered every 4 weeks for 3 to 7 times in the popliteal lymph node. Pruritus (Hill score), CADESI (canine atopic dermatitis severety index), concurrent medications and adverse reactions were recorded initially and every 4 weeks for a total period of 24 weeks. The observed clinical response was good in 12/20 (60%) patients and improvement could be seen in some dogs already after 4 weeks. The median number of injections was 5.6. All dogs tolerated the procedure well and no adverse effects were recognized during or after ILIT. Therefore ILIT should be regarded as a safe alternative to subucaneous ASIT, enabling a faster clinical improvement with the same response rate. PMID- 27655165 TI - Altered Markers of Brain Development in Crohn's Disease with Extraintestinal Manifestations - A Pilot Study. AB - BACKGROUND AND OBJECTIVE: Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development. METHODS: In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling. RESULTS: The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons. CONCLUSIONS: Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn's disease or its predisposition during brain development. PMID- 27655167 TI - Outdoor time, physical activity, sedentary time, and health indicators at ages 7 to 14: 2012/2013 Canadian Health Measures Survey. AB - BACKGROUND: International data show that the majority of children and youth are not sufficiently active. According to recent research, children who spend more time outdoors accumulate more daily moderate-to-vigorous physical activity and engage in less sedentary behaviour. However, the generalizability of these findings is uncertain, and few studies investigated whether outdoor time is associated with other physical and psychosocial health indicators. DATA AND METHODS: This study examined associations between outdoor time and measures of physical activity, sedentary time, and physical and psychosocial health in a nationally representative sample of 7-to-14-year-olds (n = 1,159) who participated in the 2012/2013 Canadian Health Measures Survey. Physical activity and sedentary time were measured with Actical accelerometers. Direct measures of height, weight, waist circumference, grip strength, blood pressure, cholesterol, and glycohemoglobin were obtained. The Strengths and Difficulties Questionnaire was used to assess psychosocial health. Relationships between outdoor time and physical health measures were examined with multi-variable linear regression models adjusted for age, sex, parental education, and household income. Logistic regression models controlling for the same variables were used for psychosocial health. RESULTS: Each additional hour spent outdoors per day was associated with 7.0 more minutes of moderate-to-vigorous physical activity, 762 more steps, and 13 fewer minutes of sedentary time. As well, each hour outdoors was associated with lower odds of negative psychosocial outcomes (specifically, peer relationship problems and total difficulties score). Outdoor time was not associated with any of the measures of physical health. INTERPRETATION: Children reporting more time outdoors are more active, less sedentary, and less likely to have peer relationship problems, compared with those who spend less time outdoors. PMID- 27655168 TI - Physical activity and sedentary behaviour of Canadian children aged 3 to 5. AB - BACKGROUND: For preschool children, physical activity is associated with improved measures of health, while sedentary behaviour is associated with less favourable health outcomes. This study updates estimates of physical activity and sedentary behaviour among children aged 3 to 5, based on combined data from two cycles of the Canadian Health Measures Survey (CHMS) in order to calculate adherence to Canadian physical activity and sedentary behaviour guidelines. DATA AND METHODS: The data are from two independent samples that comprised the 2009-to-2011 (cycle 2) and 2012/2013 (cycle 3) CHMS. Accelerometry and a parent-administered questionnaire were used in both cycles on children aged 3 to 5. Accelerometer data, collected in 60-second epochs in cycle 2 and in 15-second epochs in cycle 3, were combined using an adjustment factor derived in an independent sample. Prevalence of adherence to the physical activity guidelines, according to the accelerometer data, was estimated based on a Betabinomial distribution. Adherence to the screen-time component of the sedentary behaviour guidelines was calculated using parent reports. Results are presented by personal and household-related covariates. RESULTS: An estimated 73% of 3- to 4-year-olds and 30% of 5-year-olds met their respective physical activity guidelines. Screen-time targets were met by 22% of 3- to 4-year-olds and 76% of 5-year-olds. INTERPRETATION: Because they rely on a larger sample size and stronger estimation methods, the findings of this study are more robust than previously published estimates. Results reveal room for improvement, particularly 5-year-olds' physical activity and 3- to 4 year-olds' screen time. PMID- 27655166 TI - Lapatinib-capecitabine versus capecitabine alone as radiosensitizers in RAS wild type resectable rectal cancer, an adaptive randomized phase II trial (LaRRC trial): study protocol for a randomized controlled trial. AB - BACKGROUND: Preoperative radiochemotherapy followed by surgical removal of the rectum with total mesorectum excision is the preferred treatment option for stages II and III rectal cancer. However, development of metastatic disease is the main cause of death for these patients with 5-year disease-free survival rates of 56 %. Anti-epidermal growth factor receptor (EGFR) targeted therapy is effective in metastatic rectal cancer, and human epidermal growth factor receptor 2 (HER-2) signaling may mediate resistance to EGFR inhibitors. Moreover, preclinical data support a synergistic effect of EGFR inhibition with radiation therapy. METHODS/DESIGN: This Bayesian phase II trial with adaptive randomization was designed to assess the efficacy of adding lapatinib, a dual inhibitor of EGFR and HER-2, to standard radiochemotherapy with capecitabine in stages II and III rectal cancer. DISCUSSION: The results of this trial will provide evidence of the feasibility and efficacy of the combination of lapatinib-capecitabine as radiosensitizers and explore potential predictive biomarkers for response to this novel neoadjuvant approach to resectable rectal cancer. TRIAL REGISTRATION: EudraCT 2013-001203-36 . Registered on 13 December 2013. PMID- 27655169 TI - Epilepsy in Canada: Prevalence and impact. AB - This article provides information about the prevalence and impact of epilepsy, based on the 2010 and 2011 Canadian Community Health Surveys, the 2011/2012 Survey of Neurological Conditions in Institutions in Canada, and the 2011 Survey on Living with Neurological Conditions in Canada. An estimated 139,200 Canadians had epilepsy. Among the household population, epilepsy was generally diagnosed before age 30 (75%). For the majority of these people (64%), epilepsy was their only neurological condition. People with epilepsy were more than twice as likely to have been diagnosed with a mood disorder, compared with the general population (17% versus 7%), and eight times as likely to experience incontinence (34% versus 4%). Overall, an estimated 18% reported that their life was affected quite a bit or extremely by epilepsy; 44% felt that their life was impacted a little bit or moderately; and 39% felt that their life was not impacted at all. This study examined the impact of epilepsy on interactions with others, sleep, driving, education, and employment. PMID- 27655170 TI - Index matching at the nanoscale: light scattering by core-shell Si/SiO x nanowires. AB - Silicon nanowires (SiNWs) show strong resonant wavelength enhancement in terms of absorption as well as scattering of light. However, in most optoelectronic device concepts the SiNWs should be surrounded by a contact layer. Ideally, such a layer can also act as an index matching layer which could nearly halve the strong reflectance of light by silicon. Our results show that this reduction can be overcome at the nanometer scale, i.e. SiNWs embedded in a silica (SiO x ) layer can not only maintain their high scattering cross sections but also their strong polarization dependent scattering. Such effects can be useful for light harvesting or optoelectronic applications. Moreover, we show that it is possible to optically determine the diameters of the embedded nanoscale silicon (Si) cores. PMID- 27655172 TI - Rwanda's Model Prehospital Emergency Care Service: A Two-year Review of Patient Demographics and Injury Patterns in Kigali. AB - : Introduction Injury is responsible for nearly five million annual deaths worldwide, and nearly 90% of these deaths occur in low- and middle-income countries (LMICs). Reliable clinical data detailing the epidemiology of injury are necessary for improved care delivery, but they are lacking in these regions. METHODS: A retrospective review of the Service d'Aide Medicale Urgente (SAMU; Kigali, Rwanda) prehospital database for patients with traumatic injury-related conditions from December 2012 through November 2014 was conducted. Chi-squared analysis, binomial probability test, and student's t-test were used, where appropriate, to describe patient demographics, injury patterns, and temporal and geographic trends of injuries. RESULTS: In the two-year period, 3,357 patients were managed by SAMU for traumatic injuries. Males were 76.5% of the study population, and the median age of all injured patients was 29 years (IQR=23-35). The most common causes of injury were road traffic crashes (RTCs; 73.4%), stabbings/cuts (11.1%), and falls (9.4%), and the most common anatomic regions injured were the head (55.7%), lower (45.0%) extremities, and upper (27.0%) extremities. Almost one-fourth of injured patients suffered a fracture (24.9%). The most common mechanism of injury for adults was motorcycle-related RTCs (61.4%), whereas children were more commonly injured as pedestrians (59.8%). Centrally located sectors within Kigali represented common areas for RTCs. CONCLUSIONS: These data support the call for focused injury prevention strategies, some of which already are underway in Rwanda. Further research on care processes and clinical outcomes for injured patients may help identify avenues for improved care delivery. Enumah S , Scott JW , Maine R , Uwitonze E , Nyinawankusi JD , Riviello R , Byiringiro JC , Kabagema I , Jayaraman S . Rwanda's model prehospital emergency care service: a two-year review of patient demographics and injury patterns in Kigali. Prehosp Disaster Med. 2016;31(6):614 620. PMID- 27655173 TI - FASD and ADHD: Are they related and How? AB - In this issue of the journal, consensus criteria for the diagnosis and management of attention deficit hyperactivity disorder (ADHD) in people who have fetal alcohol spectrum disorders (FASD) are presented. In the absence of an adequate body of research on diagnosis and intervention, this expert consensus opinion is a welcome advance and should provide some guidance for clinicians managing people with FASD who have a comorbid ADHD. PMID- 27655171 TI - A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa. AB - Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disorder characterized by night blindness, visual field constriction, and severely reduced visual acuity. Despite a number of genes being implicated in RP pathogenesis, the genetic etiology of the disease remains unknown in many patients. In this study, our aim was to identify the disease-causing mutation of a large Chinese family with autosomal dominant RP (adRP). Targeted exon capture sequencing was initially performed to screen mutations in known disease-causing genes, followed by exome sequencing. In doing so, a heterozygous mutation in ADIPOR1 (c.929A > G) that results in an amino acid substitution (p.Y310C) was identified to co-segregate with the disease phenotype in this family. Adipor1 is wildly expressed throughout the body, but appears to be enriched in the photoreceptor inner and outer segments. The p.Y310C mutation, predicted to affect the structure and function of the protein, was confirmed to affect protein folding and its subcellular localization in vitro. In addition, knockdown of adipor1 expression in a zebrafish model with morpholino (MO) preferentially reduced the number of rod photoreceptors, with no effect on the number of cones, a phenotype that is characteristic of RP. Furthermore, the knockdown phenotype was partially rescued by injecting wild-type, but not mutant, human ADIPOR1 mRNA. We conclude that ADIPOR1 is a novel adRP-causing gene and plays an important role in rod development and maintenance. PMID- 27655174 TI - Towards an Accurate and Precise Chronology for the Colonization of Australia: The Example of Riwi, Kimberley, Western Australia. AB - An extensive series of 44 radiocarbon (14C) and 37 optically stimulated luminescence (OSL) ages have been obtained from the site of Riwi, south central Kimberley (NW Australia). As one of the earliest known Pleistocene sites in Australia, with archaeologically sterile sediment beneath deposits containing occupation, the chronology of the site is important in renewed debates surrounding the colonization of Sahul. Charcoal is preserved throughout the sequence and within multiple discrete hearth features. Prior to 14C dating, charcoal has been pretreated with both acid-base-acid (ABA) and acid base oxidation-stepped combustion (ABOx-SC) methods at multiple laboratories. Ages are consistent between laboratories and also between the two pretreatment methods, suggesting that contamination is easily removed from charcoal at Riwi and the Pleistocene ages are likely to be accurate. Whilst some charcoal samples recovered from outside hearth features are identified as outliers within a Bayesian model, all ages on charcoal within hearth features are consistent with stratigraphy. OSL dating has been undertaken using single quartz grains from the sandy matrix. The majority of samples show De distributions that are well bleached but that also include evidence for mixing as a result of post depositional bioturbation of the sediment. The results of the two techniques are compared and evaluated within a Bayesian model. Consistency between the two methods is good, and we demonstrate human occupation at this site from 46.4-44.6 cal kBP (95.4% probability range). Importantly, the lowest archaeological horizon at Riwi is underlain by sterile sediments which have been dated by OSL making it possible to demonstrate the absence of human occupation for between 0.9-5.2 ka (68.2% probability range) prior to occupation. PMID- 27655175 TI - A new eIF4E1 allele characterized by RNAseq data mining is associated with resistance to potato virus Y in tomato albeit with a low durability. AB - Allele mining on susceptibility factors offers opportunities to find new sources of resistance among crop wild relatives for breeding purposes. As a proof of concept, we used available RNAseq data to investigate polymorphisms among the four tomato genes encoding translation initiation factors [eIF4E1 and eIF4E2, eIFiso4E and the related gene new cap-binding protein(nCBP)] to look for new potential resistance alleles to potyviruses. By analysing polymorphism among RNAseq data obtained for 20 tomato accessions, 10 belonging to the cultivated type Solanum lycopersicum and 10 belonging to the closest related wild species Solanum pimpinellifolium, we isolated one new eIF4E1 allele, in the S. pimpinellifolium LA0411 accession, which encodes a potential new resistance allele, mainly due to a polymorphism associated with an amino acid change within eIF4E1 region II. We confirmed that this new allele, pot12, is indeed associated with resistance to potato virus Y, although with a restricted resistance spectrum and a very low durability potential. This suggests that mutations occurring in eIF4E region II only may not be sufficient to provide efficient and durable resistance in plants. However, our study emphasizes the opportunity brought by RNAseq data to mine for new resistance alleles. Moreover, this approach could be extended to seek for putative new resistance alleles by screening for variant forms of susceptibility genes encoding plant host proteins known to interact with viral proteins. PMID- 27655176 TI - Do Patients Feel Well Informed in a Radiation Oncology Service? AB - Information received by cancer patients has gained importance in recent decades. The aim of this study was to evaluate the perception of information received by oncological patients in a radiotherapy department and to measure the importance of the other information sources. A cross-sectional study was conducted, evaluating patients who received radiotherapy. All the patients were asked two questionnaires: the EORTC QLQ-INFO26 module evaluating their satisfaction with received information, and a questionnaire analyzing other sources of information search. One hundred patients between 27 and 84 years were enrolled. Breast cancer (26 %) was the commonest cancer. Patients felt better informed about the medical tests and secondly about the performed treatment. The younger patients were those who were more satisfied with the information received and patients with no formal education felt less satisfied, with statistically significant differences. Patients did not seek external information; at the most, they asked relatives and other people with cancer. Patients were satisfied with the received information, although a high percentage would like more information. In general, patients did not search for external information sources. Age and educational level seem to influence in the satisfaction with the received information. PMID- 27655178 TI - Chloride Conundrums. PMID- 27655177 TI - Awareness and Knowledge Levels of Turkish College Students about Human Papilloma Virus Infection and Vaccine Acceptance. AB - Awareness of HPV by the target population is an important determinant of vaccine acceptance. The aim of this study is to evaluate the awareness of HPV infection and acceptability of the HPV vaccines among Turkish college students. College students aged 18-30 who were attending a large public university in Ankara participated in this study. The participants were asked to complete a questionnaire to elicit demographic characteristics, awareness level of HPV and HPV vaccine, and willingness to be vaccinated. One thousand one hundred sixty students responded to the invitation email and completed the questionnaire. The mean scores of female students about HPV and HPV vaccine were 7.1/15 and 3.6/9, respectively, while these scores were 7.9/15 and 3.4/9 among male students, respectively. While 51 % percent of female and 33.5 % of male students had heard of HPV and 32.8 % and 18 % of them had heard of HPV vaccine, respectively, only 1.5 % of female and 0.4 % of male students had been vaccinated against HPV. A total of 507 students (43.7 %) had previously heard of HPV. Only 309 (26.6 %) of the participants had previously heard of the HPV vaccine, and 45.1 % of the students were willing to receive HPV vaccination. The main predictors for willingness to be vaccinated were the following: sexual experience, sexual behavior, past history of sexually transmitted infection (STI), and knowledge about HPV and HPV vaccine. Higher awareness levels of HPV and HPV vaccine are significantly related to greater willingness to be vaccinated, and the main reasons for rejecting the vaccine were insufficient information about the vaccine and possible unknown side effects. PMID- 27655179 TI - Neurodevelopmental Assessment in Kindergarten in Children Exposed to General Anesthesia before the Age of 4 Years: A Retrospective Matched Cohort Study. AB - BACKGROUND: Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain. METHODS: The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models. RESULTS: A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, -0.7; 95% CI, -0.93 to -0.47; P < 0.0001) and language/cognition (estimate, -0.34; 95% CI, -0.52 to -0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure. CONCLUSIONS: These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results. PMID- 27655180 TI - Effects of Different Crystalloid Solutions on Hemodynamics, Peripheral Perfusion, and the Microcirculation in Experimental Abdominal Sepsis. AB - BACKGROUND: Crystalloid solutions are used to restore intravascular volume in septic patients, but each solution has limitations. The authors compared the effects of three crystalloid solutions on hemodynamics, organ function, microcirculation, and survival in a sepsis model. METHODS: Peritonitis was induced by injection of autologous feces in 21 anesthetized, mechanically ventilated adult sheep. After baseline measurements, animals were randomized to lactated Ringer's (LR), normal saline (NS), or PlasmaLyte as resuscitation fluid. The sublingual microcirculation was assessed using sidestream dark field videomicroscopy and muscle tissue oxygen saturation with near-infrared spectroscopy. RESULTS: NS administration was associated with hyperchloremic acidosis. NS-treated animals had lower cardiac index and left ventricular stroke work index than LR-treated animals from 8 h and lower mean arterial pressure than LR-treated animals from 12 h. NS-treated animals had a lower proportion of perfused vessels than LR-treated animals after 12 h (median, 82 [71 to 83] vs. 85 [82 to 89], P = 0.04) and greater heterogeneity of proportion of perfused vessels than PlasmaLyte or LR groups at 18 h. Muscle tissue oxygen saturation was lower at 16 h in the NS group than in the other groups. The survival time of NS-treated animals was shorter than that of the LR group (17 [14 to 20] vs. 26 [23 to 29] h, P < 0.01) but similar to that of the PlasmaLyte group (20 [12 to 28] h, P = 0.74). CONCLUSIONS: In this abdominal sepsis model, resuscitation with NS was associated with hyperchloremic acidosis, greater hemodynamic instability, a more altered microcirculation, and more severe organ dysfunction than with balanced fluids. Survival time was shorter than in the LR group. PMID- 27655181 TI - A Slick Way Volatile Anesthetics Reduce Myocardial Injury: Erratum. PMID- 27655182 TI - A Day at the Office: Political Advocacy and Private Practice. PMID- 27655183 TI - Are Biopsy Tracts a Concern for Seeding and Local Recurrence in Sarcomas? AB - BACKGROUND: A biopsy is the final step in the diagnosis of sarcomas. Complete resection of the biopsy tract traditionally has been recommended in musculoskeletal oncology guidelines, as that tract is considered potentially seeded with tumor cells. However, to our knowledge, the frequency and implications of contamination of the biopsy tract-specifically with respect to the likelihood of local recurrence-and the factors that affect cell seeding are not well described. QUESTIONS/PURPOSES: We asked: (1) How often are biopsy tracts contaminated with pathologically detectable tumor cells at the time of tumor resection? (2) What factors, in particular biopsy type (open versus percutaneous), are associated with tumoral seeding? (3) Is biopsy tract contamination associated with local recurrence? METHODS: This is a retrospective study of a database with patient data collected from a single center between 2000 and 2013. We treated 221 patients with sarcomas. A total of 27 patients (12%) were excluded and 14 (6%) were lost to followup. One hundred eighty patients finally were included in the analysis who either had biopsies at our center (112) or biopsies at outside institutions (68). Of those performed at our center, 15 (13%) were open and 97 (87%) were percutaneous; of those at outside centers, those numbers were 47 (69%) and 21 (31%) respectively. Median followup was 40 months (range, 24-152 months). During the study period, we generally performed percutaneous biopsies as a standard practice for the diagnosis of bone and soft tissue sarcomas and open biopsies were done when the percutaneous procedure failed to provide a histologic characterization. The mean age of the population was 48 years (range, 7-87 years); 60% were male; 42% had bone sarcomas. Nineteen patients had preoperative radiotherapy and 56 had postoperative radiotherapy. Fifty-seven patients received neoadjuvant chemotherapy and 73 had adjuvant chemotherapy. We determined what proportion of biopsy tracts were contaminated by pathologic analysis of the biopsy tract specimen; during the period in question, our routine practice was to excise the biopsy tract whenever possible at the time of the definitive resection. Using the logistic regression test and Mantel Haenszel test, we compared open with percutaneous biopsies in terms of the proportion of those that were contaminated at our site and for outside referral biopsies separately, because we do not assume the level of expertise was the same (our site is a referral tumor center). We compared the local recurrence-free survival between patients with and without contamination and between open and percutaneous biopsies using the Kaplan Meier test, again separating those performed at our site from those referred for purposes of this analysis. RESULTS: Twenty-one of 180 biopsy tracts were contaminated (12%). Twenty of 62 (32%) of the open biopsies and one of 118 (0.8%) of the percutaneous core needle biopsies had cell seeding (odds ratio [OR], 56; 95% CI, 7-428; p < 0.001. One of 97 (1%) percutaneous biopsies performed in our center, and none of the 21 (0%) percutaneous biopsies performed in other centers had contaminated biopsy tracts (p = 0.047). Two of 15 (13%) open biopsies performed at our center and 18 of 41(38%) open biopsies performed at other centers had contaminated biopsy tracts (OR, 4; 95% CI, 1-7; p = 0.001). Four of 74 (5%) bone sarcomas and 18 of 106 (17%) soft tissue sarcomas had biopsy tract contamination (OR, 3; 95% CI, 1-10; p = 0.023). The local recurrence-free survival was longer for patients without contaminated tracts (mean, 107 months; 95% CI, 74-141 months) than for those with biopsy tract seeding (mean, 11 months; 95% CI, 1-20 months; p < 0.001). CONCLUSIONS: Open biopsies were associated with an increased risk of tumoral seeding of the biopsy site, and tumoral seeding was associated with an increased risk of local recurrence. However, it is possible that other factors, such as increased complexity of the tumor or a difficult location, influenced the decision to obtain an open biopsy. Even so, based on these results, we believe that higher risk of local recurrence may be caused by an incomplete biopsy tract resection. In our opinion, the percutaneous biopsy with neoadjuvant or adjuvant therapy is the preferred method of biopsy at our center. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27655184 TI - Can Facebook Be Used for Research? Experiences Using Facebook to Recruit Pregnant Women for a Randomized Controlled Trial. AB - BACKGROUND: Recruitment is often a difficult and costly part of any human research study. Social media and other emerging means of mass communication hold promise as means to complement traditional strategies used for recruiting participants because they can reach a large number of people in a short amount of time. With the ability to target a specified audience, paid Facebook advertisements have potential to reach future research participants of a specific demographic. This paper describes the experiences of a randomized controlled trial in Edmonton, Alberta, attempting to recruit healthy pregnant women between 8 and 20 weeks' gestation for participation in a prenatal study. Various traditional recruitment approaches, in addition to paid Facebook advertisements were trialed. OBJECTIVE: To evaluate the effectiveness of paid advertisements on Facebook as a platform for recruiting pregnant women to a randomized controlled trial in comparison with traditional recruitment approaches. METHODS: Recruitment using traditional approaches occurred for 7 months, whereas Facebook advertisements ran for a total of 26 days. Interested women were prompted to contact the study staff for a screening call to determine study eligibility. Costs associated with each recruitment approach were recorded and used to calculate the cost to recruit eligible participants. Performance of Facebook advertisements was monitored using Facebook Ads Manager. RESULTS: Of the 115 women included, 39.1% (n=45) of the women who contacted study staff heard about the study through Facebook, whereas 60.9% (n=70) of them heard about it through traditional recruitment approaches. During the 215 days (~7 months) that the traditional approaches were used, the average rate of interest was 0.3 (0.2) women/day, whereas the 26 days of Facebook advertisements resulted in an average rate of interest of 2.8 (1.7) women/day. Facebook advertisements cost Can $506.91 with a cost per eligible participant of Cad $20.28. In comparison, the traditional approaches cost Cad $1087, with approximately Cad $24.15 per eligible participant. Demographic characteristics of women were similar between the 2 recruitment methods except that women recruited using Facebook were significantly earlier in their pregnancy than those recruited using traditional approaches (P<.03). CONCLUSIONS: Paid Facebook advertisements hold promise as a platform for reaching pregnant women. The relative ease of placing an advertisement, the comparable cost per participant recruited, and the dramatically improved recruitment rates in comparison with traditional approaches highlight the importance of combining novel and traditional recruitment approaches to recruit women for pregnancy-related studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02711644; https://clinicaltrials.gov/ct2/show/NCT02711644 (Archived by WebCite at http://www.webcitation.org/6kKpagpMk). PMID- 27655186 TI - Urogynecology digest : Presented by Patrick Campbell. PMID- 27655185 TI - Developing interprofessional care plans in chronic care: a scoping review. AB - BACKGROUND: The number of people suffering from one or more chronic conditions is rising, resulting in an increase in patients with complex health care demands. Interprofessional collaboration and the use of shared care plans support the management of complex health care demands of patients with chronic illnesses. This study aims to get an overview of the scientific literature on developing interprofessional shared care plans. METHODS: We conducted a scoping review of the scientific literature regarding the development of interprofessional shared care plans. A systematic database search resulted in 45 articles being included, 5 of which were empirical studies concentrating purely on the care plan. Findings were synthesised using directed content analysis. RESULTS: This review revealed three themes. The first theme was the format of the shared care plan, with the following elements: patient's current state; goals and concerns; actions and interventions; and evaluation. The second theme concerned the development of shared care plans, and can be categorised as interpersonal, organisational and patient-related factors. The third theme covered tools, whose main function is to support professionals in sharing patient information without personal contact. Such tools relate to documentation of and communication about patient information. CONCLUSION: Care plan development is not a free-standing concept, but should be seen as the result of an underlying process of interprofessional collaboration between team members, including the patient. To integrate the patients' perspectives into the care plans, their needs and values need careful consideration. This review indicates a need for new empirical studies examining the development and use of shared care plans and evaluating their effects. PMID- 27655188 TI - Urogynecology digest : Presented by Jenifer Byrnes. PMID- 27655187 TI - An innovative approach to treating vaginal mesh exposure after abdominal sacral colpopexy: endoscopic resection of mesh and platelet-rich plasma; initial experience in three women. AB - INTRODUCTION AND HYPOTHESIS: Polypropylene mesh exposure is uncommon after abdominal sacral colpopexy (ASC), but in case of symptomatic vaginal mesh exposure, surgery is needed. When treating it, care must be taken to completely remove the exposed mesh (EM), saving as much vaginal tissue as possible to avoid a subsequent shortened and narrowed vagina. In this video, we present a minimally invasive technique for treating EM after ASC using endoscopic mesh resection and autologous platelet-rich plasma (PRP) technology. METHODS: Three women were referred to our outpatient clinic for vaginal vault mesh exposure after laparoscopic ASC with concomitant hysterectomy. All women underwent endoscopic bipolar PlasmaKinetic resection (BPR) of EM, and PRP gel was delivered in the surgical site to cover the gap left by the resection. RESULTS: Mean operative time was 39.6 min. Surgery was uneventful in all cases. All women recovered sexual function, and nobody experienced relapsed pelvic organ prolapse at 1-year follow-up. CONCLUSIONS: Our preliminary results show that BPR and PRP are safe, effective, and feasible for treating vaginal mesh exposure with conservation of anatomy and sexual function. PMID- 27655190 TI - Rural Matters. PMID- 27655191 TI - Do Residencies That Aim to Produce Rural Family Physicians Offer Relevant Training? AB - BACKGROUND AND OBJECTIVES: Rural family physicians are in short supply. Rural training can promote rural practice, but the number of family medicine residencies with a rural focus, geographic distribution of training, and training content are poorly understood. This study identified rural-centric family medicine residencies, their training locations, and rurally relevant skills training provided. METHODS: The authors identified family medicine residencies offering rural tracks or in rural locations using FREIDA Online(r), the American Osteopathic Association "Opportunities," and the American College of Osteopathic Family Physicians Residency Finder online databases. Program personnel completed a survey in 2013 about training locations and content. RESULTS: Of 583, 171 (29%) family medicine residencies met inclusion criteria. A total of 131 returned surveys (77%). Fifty-eight programs (44% of respondents) required at least 8 weeks of rural training; results describe these rural-centric programs. Programs reported a mean of 43.6 weeks (SD 49.7) of required rural block rotations. Mean hours per week in required rural continuity clinic sessions were 14.3 (SD 12.2). Thirty-nine percent of block rotation sites, 31% of clinic sites, and 21% of full time training sites reported as rural were urban according to Rural-Urban Commuting Area codes. Over 90% of programs provided training in orthopedic care and emergency skills. Fewer than 60% provided endoscopy and operative obstetrics training. CONCLUSIONS: Though numerous family medicine residencies seek to produce rural physicians, most programs required fewer than 8 weeks of rural training. Programs varied substantially in rurally located training and rurally relevant content. Students seeking rural training should examine program curricula carefully. PMID- 27655192 TI - Resident Engagement in the Patient-Centered Medical Home. AB - BACKGROUND AND OBJECTIVES: This study's objectives were to assess resident understanding and engagement with the patient-centered medical home (PCMH) model and to assess the impact of participation in a PCMH transformation collaborative on residents' experiences and perceptions related to their training environment. METHODS: Residents from practices participating in the largest state-wide PCMH learning collaborative were asked to complete surveys describing their experiences with the collaborative and the PCMH transformation process. Residents from four representative participating residencies were recruited to participate in focus groups designed to provide qualitative data to augment our understanding of the quantitative survey results. RESULTS: We had a reasonable average response rate (39%) with a total of 100 completed resident surveys. Quantitative data illustrated high levels of residents' endorsement of PCMH awareness, engagement, and PCMH-related skills acquisition. The analyses suggested higher levels of PCMH engagement, understanding, and sense of adequacy of preparation among residents who attended learning collaborative sessions compared to those who did not. While qualitative data validated many of the quantitative findings, they also illustrated a somewhat detached and peripheral description of resident experiences with the transformation process. CONCLUSIONS: The presented data describe the complexities of preparing the next generation of providers for practice. Our mixed-methods study illustrated the strengths of participating in the learning collaborative but also areas of focus necessary for improving the experience and educational benefits of PCMH-related curricula involving residents. PMID- 27655193 TI - Expectations of the Competencies of Entering Family Medicine Residents: Do Members of the Family Agree? A CERA Study. AB - BACKGROUND AND OBJECTIVES: Little information is available on what competencies family medicine program directors expect of incoming residents and whether those incoming residents can deliver on such expectations. Our aim was to determine whether there is a common set of skills that both family medicine clerkship directors and program directors agree are important for entering residents to possess and how often these are being demonstrated. METHODS: This study is an analysis of data obtained in the 2014 CERA Family Medicine Clerkship Director and Program Director surveys. Clerkship directors and program directors were provided with a list of skill areas and professional characteristics and asked to rate how important it is for medical school graduates to demonstrate them as well as how many medical school graduates consistently demonstrate each skill or characteristic. RESULTS: Both groups placed highest importance on honesty, professionalism, and communication skills among incoming residents. Clerkship directors placed higher importance on several skill areas, with program directors emphasizing professional characteristics. This division was also seen in the opinions of the two groups for how well entering residents demonstrated each area. CONCLUSIONS: Clerkship directors identify several skill sets as being more important for graduating medical students to possess compared with program directors. Program directors seem to value more personal characteristics as important for entering residents to possess rather than skills. Future implications may include a focus from family medicine clerkships on skills that are valued by program directors but not rated as commonly seen among incoming residents. PMID- 27655194 TI - Training Family Medicine Clerkship Students in Screening, Brief Intervention, and Referral to Treatment for Substance Use Disorders: A CERA Study. PMID- 27655195 TI - Reliability of Mini-CEX Assessment of Medical Students in General Practice Clinical Attachments. AB - BACKGROUND AND OBJECTIVES: Mini Clinical Evaluation eXercise (mini-CEX) involves observation of routine clinical encounters, initially developed to assess clinical competencies of postgraduate doctors. This study aimed to measure its inter-rater reliability in assessment of medical students in general practice settings. METHODS: General practitioners (GPs) supervising medical students were invited to complete online teaching on how to conduct a mini-CEX. This included three randomly presented scripted films of clinical scenarios representing different levels of student performance. Consenting participants completed an online mini-CEX. Mean marks were calculated for each case, Intraclass Correlation Coefficients (ICC) for overall clinical and four individual competencies, one-way analysis of variance to compare scores, and internal consistency measured by Cronbach's alpha. RESULTS: RESULTS were collated for the first 100 completing GPs, majority aged 40-59 years (71%), male (59%), New Zealand European (58%). Forty-four percent were in rural practice, with 21 mean years in practice. Mean mini-CEX grades increased as standardized performance increased, indicating that GPs reliably agreed about ranking of student performance from poor to very good. The intraclass correlation coefficient (ICC) for overall clinical competency was 0.78 (95% confidence interval 0.48-0.99), indicating good reliability regarding their agreement with each other. A Cronbach's alpha calculated with the overall scores was 0.85, indicating good internal consistency. CONCLUSIONS: Mini-CEXs in undergraduate general practice attachments provide a reliable measure of assessing performance. However, they may be less useful in identifying exceptional performance or weaknesses in key competencies. In addition, caution must be applied in relying upon mini-CEXs to supply a summative assessment. PMID- 27655196 TI - Intent to Build Hepatitis C Treatment Capacity Within Family Medicine Residencies: A Nationwide Survey of Program Directors: A CERA Study. AB - BACKGROUND AND OBJECTIVES: In the current interferon-free era, family medicine is in a unique position to deliver hepatitis C (HCV) treatment with adequate training. Little is known about attitudes of family medicine program directors (PDs) toward capacity building within their residency programs. We report the results of a nationwide survey of family medicine PDs to examine these attitudes. METHODS: This study was part of a CERA (Council of Academic Family Medicine Educational Research Alliance) omnibus survey administered to family medicine PDs between February 2015 and March 2015. Attitudes were assessed using a Likert scale ranging from 1=strongly disagree to 6=strongly agree. RESULTS: We surveyed 452 physicians, with 273 responses (response rate 61%). The majority of PDs (78%) believed that chronic HCV represented a significant problem for primary care, and 61.9% believed their program should take steps to build capacity in HCV treatment. There was no effect of regional HCV prevalence, residency program context, or PD characteristics on intent to build capacity. CONCLUSIONS: This is the first report to examine PDs intent to build capacity in HCV treatment in this interferon-free, direct antiviral era. Our findings highlight a historic opportunity to train family physicians and position them on the frontline as HCV treatment providers. PMID- 27655189 TI - The restorative role of annexin A1 at the blood-brain barrier. AB - Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood-brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood-brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood-brain barrier damage in disease and aging. PMID- 27655197 TI - Community Health Needs Assessment as a Teaching Tool in a Family Medicine Residency. AB - BACKGROUND AND OBJECTIVES: Community-based primary care is a fundamental concept taught in family medicine. Best practices for community-oriented and public health training in medical training programs are underreported in the published literature. A Community Health Needs Assessment (CHNA) offers an opportunity for family medicine residents to practice research and evaluation skills while learning about public health and the community they serve. METHODS: A family medicine residency program in Harlem, NY, conducted a CHNA in order to assess their community's health landscape and as an opportunity to teach the resident trainees research skills. Primary and secondary data were collected by the residents using public databases, surveys, focus groups, and key informant interviews. Residents completed a survey at the project's completion to assess their experience with the CHNA and to obtain suggestions for improving the process in the future. RESULTS: More than 50% of the 15 residents surveyed reported that the CHNA greatly improved their comfort level speaking to patients about social factors that affect their health. Participants responded that they valued the opportunity to engage with community members and to understand their patients on a population level. The greatest challenge for most residents was lack of devoted time to complete the project considering competing residency responsibilities. CONCLUSIONS: Conducting a CHNA in a primary care training program can help the next generation of family physicians become culturally competent and community focused in their work. PMID- 27655198 TI - Addressing Hospital Readmissions: Impact of Weekly Review. AB - BACKGROUND AND OBJECTIVES: The prevention of hospital readmissions has become an area for improvement for most health care organizations. Systematic reviews have been unable to identify a single intervention or bundle of interventions that reliably reduced risk of readmission in a generalizable manner. The aim of this quality improvement project was to examine the readmission rate to a family medicine residency program inpatient service following the implementation of a once per week session that reviewed patients who were readmitted during the prior week. METHODS: The inpatient admissions and readmission to the family medicine inpatient service associated with a large academic health center were used for analysis. The impact of a regularly scheduled multidisciplinary team meeting that reviewed a list of patients was examined. Readmitted patients who were at high risk for readmission were specifically identified. Descriptive statistics were used to characterize and summarize the integral data obtained. The weekly readmission rate was presented using a control chart. RESULTS: The readmission rate for the patients hospitalized after the intervention was 18.4%, compared to the readmission rate prior to the intervention (23.0%). While not a statistically different rate, a significant signal was noted. Demographic differences were noted in the group of patients considered to be high risk for readmission. CONCLUSIONS: Regular rounds of an inpatient team that focuses on readmissions during the previous week reduced hospital readmissions. The impact of these sessions appears to be multifactorial. PMID- 27655199 TI - Systems Change Enhances Access to Family Planning Training and Care Delivery. AB - BACKGROUND AND OBJECTIVES: Long-acting reversible contraceptives (LARCs) are very effective methods of pregnancy prevention. To ensure autonomy over childbearing, women need access to contraception and abortion services. Family physicians can improve access by increasing numbers and locations of trained providers. In 2014, the University of Maryland (UMD) Reproductive Health EDucation In family medicine (RHEDI) program sought to enhance LARC and abortion training by increasing: (1) resident participation in LARC services, (2) resident participation/interest in abortion care, (3) patient access to LARCs and medication abortions (MABs). METHODS: DESIGN: We used a pre-post framework comparing years 2013 and 2014 with respect to number of resident-provided LARC services, number of residents participating in abortion, and total number of LARCs and MABs provided practice wide. SETTING: The setting is an urban residency practice. INTERVENTION: (1) increased dedicated appointments for LARC and MABs, (2) dedicated appointment scheduler, (3) comprehensive family planning didactics and clinical workshops, (4) faculty-supported Residents for Choice group. RESULTS: 2014: Residents provided substantially more LARC services compared to 2013. Placement increased from 50 to 90, and removals tripled (25 to 73). 2014 site-wide LARC placement also increased (160 versus 98), removals increased (44 in 2013, 106 in 2014). Twelve residents per year are eligible to participate in abortion care. In 2013, two participated: in 2014, 10 participated. MABs provided in 2014 (18) did not change from 2013 (17). CONCLUSIONS: The UMD RHEDI program demonstrated that attention to care-provision systems and education enhances resident training and increases patient access to family planning services. Programs with similar goals may find our methods helpful. PMID- 27655200 TI - The Emergency Physical. PMID- 27655201 TI - Racial Politics in the Exam Room. PMID- 27655202 TI - Waking Up Dead. PMID- 27655203 TI - On Working Mothers and Daughters. PMID- 27655204 TI - Introduction to the US Food System: Public Health, Environment, and Equity. PMID- 27655206 TI - The Laws of Medicine: Field Notes From an Uncertain Science (TED Books). PMID- 27655205 TI - The Self-Directed Learner in Medical Education-The Three Pillar Model for Developing Self-Directedness. PMID- 27655207 TI - Expanding the Possibilities for Pharmacy-Family Medicine Residency Collaboration. PMID- 27655208 TI - Clinical Pharmacists in Family Medicine Residency Programs: Tackling the Billing Barrier. PMID- 27655209 TI - Response to "Expanding the Possibilities for Pharmacy- Family Medicine Residency Collaboration" and "Clinical Pharmacists in Family Medicine Residency Programs: Tackling the Billing Barrier". PMID- 27655210 TI - Training (and Maintaining) Full Scope Family Medicine. PMID- 27655211 TI - Gold-decorated highly ordered self-organized grating-like nanostructures on Ge surface: Kelvin probe force microscopy and conductive atomic force microscopy studies. AB - Nanoarchitecture by atomic manipulation is considered to be one of the emerging trends in advanced functional materials. It has a gamut of applications to offer in nanoelectronics, chemical sensing, and nanobiological science. In particular, highly ordered one-dimensional semiconductor nanostructures fabricated by self organization methods are in high demand for their high aspect ratios and large number of applications. An efficient way of fabricating semiconductor nanostructures is by molecular beam epitaxy, where atoms are added to a crystalline surface at an elevated temperature during growth, yielding the desired structures in a self-assembled manner. In this article, we offer a room temperature process, in which atoms are sputtered away by ion impacts. Using gold ion implantation, the present study reports on the formation of highly ordered self-organized long grating-like nanostructures, with grooves between them, on a germanium surface. The ridges of the patterns are shown to have flower-like protruding nanostructures, which are mostly decorated by gold atoms. By employing local probe microscopic techniques like Kelvin probe force microscopy and conductive atomic force microscopy, we observe a spatial variation in the work function and different nanoscale electrical conductivity on the ridges of the patterns and the grooves between them, which can be attributed to gold atom decorated ridges. Thus, the architecture presented offers the advantage of using the patterned germanium substrates as periodic arrays of conducting ridges and poorly conducting grooves between them. PMID- 27655212 TI - A 22-year-old woman with unexplained exertional dyspnoea. PMID- 27655213 TI - Development and Implementation of a Novel Prehospital Care System in the State of Kerala, India. AB - Most low- and middle-income countries (LMICs) have struggled to find a system for prehospital care that can provide adequate patient care and geographical coverage while maintaining a feasible price tag. The emergency medical systems of the Western world are not necessarily relevant in developing economic systems, given the lack of strict legislation, the scarcity of resources, and the limited number of trained personnel. Meanwhile, most efforts to provide prehospital care in India have taken the form of adapting Western models to the Indian context with limited success. Described here is a novel approach to prehospital care designed for and implemented in the State of Kerala, India. The Active Network Group of Emergency Life Savers (ANGELS) was launched in 2011 in Calicut City, the third largest city in the Indian State of Kerala. The ANGELS integrated an existing fleet of private and state-owned ambulances into a single network utilizing Global Positioning System (GPS) technology and a single statewide call number. A total of 85 volunteer emergency medical certified technicians (EMCTs) were trained in basic first aid and trauma care principles. Public awareness campaigns accompanied all activities to raise awareness amongst community members. Funding was provided via public-private partnership, aimed to minimize costs to patients for service utilization. Over a two-year period from March 2011 to April 2013, 8,336 calls were recorded, of which 54.8% (4,569) were converted into actual ambulance run sheets. The majority of calls were for medical emergencies and most patients were transported to Medical College Hospital in Calicut. This unique public-private partnership has been responsive to the needs of the population while sustaining low operational costs. This system may provide a relevant template for Emergency Medical Services (EMS) development in other resource limited settings. Brown HA , Douglass KA , Ejas S , Poovathumparambil V . Development and implementation of a novel prehospital care system in the State of Kerala, India. Prehosp Disaster Med. 2016;31(6):663-666. PMID- 27655214 TI - Hoarding and horizontal transfer led to an expanded gene and intron repertoire in the plastid genome of the diatom, Toxarium undulatum (Bacillariophyta). AB - Although the plastid genomes of diatoms maintain a conserved architecture and core gene set, considerable variation about this core theme exists and can be traced to several different processes. Gene duplication, pseudogenization, and loss, as well as intracellular transfer of genes to the nuclear genome, have all contributed to variation in gene content among diatom species. In addition, some noncoding sequences have highly restricted phylogenetic distributions that suggest a recent foreign origin. We sequenced the plastid genome of the marine diatom, Toxarium undulatum, and found that the genome contains three genes (chlB, chlL, and chlN) involved in light-independent chlorophyll a biosynthesis that were not previously known from diatoms. Phylogenetic and syntenic data suggest that these genes were differentially retained in this one lineage as they were repeatedly lost from most other diatoms. Unique among diatoms and other heterokont algae sequenced so far, the genome also contains a large group II intron within an otherwise intact psaA gene. Although the intron is most similar to one in the plastid-encoded psaA gene of some green algae, high sequence divergence between the diatom and green algal introns rules out recent shared ancestry. We conclude that the psaA intron was likely introduced into the plastid genome of T. undulatum, or some earlier ancestor, by horizontal transfer from an unknown donor. This genome further highlights the myriad processes driving variation in gene and intron content in the plastid genomes of diatoms, one of the world's foremost primary producers. PMID- 27655215 TI - See-Thru-Gonad zebrafish line: developmental and functional validation. AB - Zebrafish are an important model species in developmental biology. However, their potential in reproductive biology research has yet to be realized. In this study, we established See-Thru-Gonad zebrafish, a transparent line with fluorescently labeled germ cells visible throughout the life cycle, validated its gonadal development features, and demonstrated its applicability by performing a targeted gene knockdown experiment using vivo-morpholinos (VMOs). To establish the line, we crossed the zf45Tg and mitfa(w2/w2); mpv17(b18/b18) zebrafish lines. We documented the in vivo visibility of the germline-specific fluorescent signal throughout development, from gametes through embryonic and juvenile stages up to sexual maturity, and validated gonadal development with histology. We performed targeted gene knockdown of the microRNA (miRNA) miR-92a-3p through injection of VMOs directly to maturing ovaries. After the treatment, zebrafish were bred naturally. Embryos from miR-92a-3p knockdown ovaries had a significant reduction in relative miR-92a-3p expression and a higher percentage of developmental arrest at the 1-cell stage as compared with 5-base mismatch-treated controls. The experiment demonstrates that See-Thru-Gonad line can be successfully used for vertical transmission of the effects of targeted gene knockdown in ovaries into their offspring. PMID- 27655217 TI - Anesthesia Kills Brain Cells, but What Does It Mean? PMID- 27655216 TI - Propolis extracts from the northern region of Thailand suppress cancer cell growth through induction of apoptosis pathways. AB - The continual increase in mortality rates and number of cancer cases is a matter of serious concern in developing countries. The incorporation of natural products into classical cancer treatment approaches is a promising direction. The mechanisms of A549 and HeLa cancer cell death induction by ethanolic extracts of propolis samples from Phayao, Chiang Mai, and Nan provinces in northern Thailand were investigated in this study. The propolis extract from Chiang Mai showed the highest antioxidant activity and the greatest total phenolic content. The propolis extract from Nan also exhibited the highest total flavonoid content. The proliferation of A549 and HeLa cells grown in the presence of the propolis extracts was suppressed in a dose- and time-dependent manner. Moreover, treatment of both cancer cells with the propolis extracts showed DNA fragmentation and significantly increased the number of the apoptotic cells. On A549 cells, the extrinsic and intrinsic pathways of caspase enzymes were activated by the propolis extracts from Phayao and Chiang Mai. In the case of the propolis extract from Nan, the mechanisms involved apoptosis on the A549 cells were caspase independent pathway. The extrinsic pathway of the caspase enzyme was triggered by all of the propolis extracts on HeLa cells. Finally, oral administration of the propolis granule produced from the propolis extract from Nan resulted in extended survival of tumour-bearing mice. Therefore, propolis extracts from the northern region of Thailand demonstrated pharmacological properties, both antioxidant and anticancer activities. From these findings, it is evident that propolis extracts can be considered as a naturally obtained agent extremely useful in cancer treatment. PMID- 27655218 TI - Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity. AB - BACKGROUND: Exposure to isoflurane increases apoptosis among postnatally generated hippocampal dentate granule cells. These neurons play important roles in cognition and behavior, so their permanent loss could explain deficits after surgical procedures. METHODS: To determine whether developmental anesthesia exposure leads to persistent deficits in granule cell numbers, a genetic fate mapping approach to label a cohort of postnatally generated granule cells in Gli1 CreER::GFP bitransgenic mice was utilized. Green fluorescent protein (GFP) expression was induced on postnatal day 7 (P7) to fate map progenitor cells, and mice were exposed to 6 h of 1.5% isoflurane or room air 2 weeks later (P21). Brain structure was assessed immediately after anesthesia exposure (n = 7 controls and 8 anesthesia-treated mice) or after a 60-day recovery (n = 8 controls and 8 anesthesia-treated mice). A final group of C57BL/6 mice was exposed to isoflurane at P21 and examined using neurogenesis and cell death markers after a 14-day recovery (n = 10 controls and 16 anesthesia-treated mice). RESULTS: Isoflurane significantly increased apoptosis immediately after exposure, leading to cell death among 11% of GFP-labeled cells. Sixty days after isoflurane exposure, the number of GFP-expressing granule cells in treated animals was indistinguishable from control animals. Rates of neurogenesis were equivalent among groups at both 2 weeks and 2 months after treatment. CONCLUSIONS: These findings suggest that the dentate gyrus can restore normal neuron numbers after a single, developmental exposure to isoflurane. The authors' results do not preclude the possibility that the affected population may exhibit more subtle structural or functional deficits. Nonetheless, the dentate appears to exhibit greater resiliency relative to nonneurogenic brain regions, which exhibit permanent neuron loss after isoflurane exposure. PMID- 27655219 TI - Hemin and Cobalt Protoporphyrin Inhibit NLRP3 Inflammasome Activation by Enhancing Autophagy: A Novel Mechanism of Inflammasome Regulation. AB - Inflammasomes are intracellular protein platforms, which, upon activation, produce the highly proinflammatory cytokines interleukin (IL)-1beta and IL-18. Heme, hemin and their degradation products possess significant immunomodulatory functions. Here, we studied whether hemin regulates inflammasome function in macrophages. Both hemin and its derivative, cobalt protoporphyrin (CoPP), significantly reduced IL-1beta secretion by cultured human primary macrophages, the human monocytic leukemia cell line and also mouse bone marrow-derived and peritoneal macrophages. Intraperitoneal administration of CoPP to mice prior to urate crystal-induced peritonitis alleviated IL-1beta secretion to the peritoneal cavity. In cultured macrophages, hemin and CoPP inhibited NLRP3 inflammasome assembly by reducing the amount of intracellular apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC). The reduction of ASC was associated with enhanced autophagosome formation and autophagic flux. Inhibition of autophagy prevented the CoPP-induced depletion of ASC, implying that the depletion was caused by increased autophagy. Our data indicate that hemin functions as an endogenous negative regulator of the NLRP3 inflammasome. The inhibition is mediated via enhanced autophagy that results in increased degradation of ASC. This regulatory mechanism may provide a novel approach for the treatment of inflammasome-related diseases. PMID- 27655220 TI - Heartbeat: Microvascular dysfunction in heart failure with preserved ejection fraction. PMID- 27655221 TI - Microvascular endothelial dysfunction in heart failure with preserved ejection fraction. PMID- 27655222 TI - Management of Protected Areas and Its Effect on an Ecosystem Function: Removal of Prosopis flexuosa Seeds by Mammals in Argentinian Drylands. AB - The ecological function of animal seed dispersal depends on species interactions and can be affected by drivers such as the management interventions applied to protected areas. This study was conducted in two protected areas in the Monte Desert: a fenced reserve with grazing exclusion and absence of large native mammals (the Man and Biosphere Nacunan Reserve; FR) and an unfenced reserve with low densities of large native and domestic animals (Ischigualasto Park; UFR). The study focuses on Prosopis flexuosa seed removal by different functional mammal groups: "seed predators", "scatter-hoarders", and "opportunistic frugivores". Under both interventions, the relative contribution to seed removal by different functional mammal groups was assessed, as well as how these groups respond to habitat heterogeneity (i.e. vegetation structure) at different spatial scales. Camera traps were used to identify mammal species removing P. flexuosa seeds and to quantify seed removal; remote sensing data helped analyze habitat heterogeneity. In the FR, the major fruit removers were a seed predator (Graomys griseoflavus) and a scatter-hoarder (Microcavia asutralis). In the UFR, the main seed removers were the opportunistic frugivores (Lycalopex griseus and Dolichotis patagonum), who removed more seeds than the seed predator in the FR. The FR shows higher habitat homogeneity than the UFR, and functional groups respond differently to habitat heterogeneity at different spatial scales. In the FR, because large herbivores are locally extinct (e.g. Lama guanicoe) and domestic herbivores are excluded, important functions of large herbivores are missing, such as the maintenance of habitat heterogeneity, which provides habitats for medium-sized opportunistic frugivores with consequent improvement of quality and quantity of seed dispersal services. In the UFR, with low densities of large herbivores, probably one important ecosystem function this group performs is to increase habitat heterogeneity, allowing for the activity of medium-sized mammals who, behaving as opportunistic frugivores, did the most significant seed removal. PMID- 27655223 TI - Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study. AB - Veliparib is a potent, orally bioavailable, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that crosses the blood-brain barrier and has been shown to potentiate the effects of radiation in preclinical and early clinical studies. This phase 2, randomized, global study evaluated the efficacy and safety of veliparib in combination with whole-brain radiation therapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC). Three-hundred and seven patients with brain metastases from NSCLC were randomized 1:1:1 to WBRT (30 Gy in 10 fractions) plus 50 mg veliparib twice daily (BID; n = 103), 200 mg veliparib BID (n = 102), or placebo BID (n = 102). Treatment began within 28 days of diagnosis. Tumor response and safety were assessed; the primary endpoint was overall survival (OS). Patients who received >=1 dose of treatment were included in the safety analysis. All randomized patients were included in the efficacy endpoint analyses. Patient characteristics were well balanced between treatment arms. Median OS was 185 days for patients treated with WBRT plus placebo and 209 days for WBRT plus veliparib (50 or 200 mg). No statistically significant differences in OS, intracranial response rate, and time to clinical or radiographic progression between any of the treatment arms were noted. No differences were observed in adverse events (all grades) across treatment arms; nausea, fatigue, alopecia, and headache were the most commonly reported. No new safety signals were identified for veliparib. A significant unmet need for therapies that improve the outcomes of patients with brain metastases from NSCLC remains. PMID- 27655224 TI - Quantifying differences in cell line population dynamics using CellPD. AB - BACKGROUND: The increased availability of high-throughput datasets has revealed a need for reproducible and accessible analyses which can quantitatively relate molecular changes to phenotypic behavior. Existing tools for quantitative analysis generally require expert knowledge. RESULTS: CellPD (cell phenotype digitizer) facilitates quantitative phenotype analysis, allowing users to fit mathematical models of cell population dynamics without specialized training. CellPD requires one input (a spreadsheet) and generates multiple outputs including parameter estimation reports, high-quality plots, and minable XML files. We validated CellPD's estimates by comparing it with a previously published tool (cellGrowth) and with Microsoft Excel's built-in functions. CellPD correctly estimates the net growth rate of cell cultures and is more robust to data sparsity than cellGrowth. When we tested CellPD's usability, biologists (without training in computational modeling) ran CellPD correctly on sample data within 30 min. To demonstrate CellPD's ability to aid in the analysis of high throughput data, we created a synthetic high content screening (HCS) data set, where a simulated cell line is exposed to two hypothetical drug compounds at several doses. CellPD correctly estimates the drug-dependent birth, death, and net growth rates. Furthermore, CellPD's estimates quantify and distinguish between the cytostatic and cytotoxic effects of both drugs-analyses that cannot readily be performed with spreadsheet software such as Microsoft Excel or without specialized computational expertise and programming environments. CONCLUSIONS: CellPD is an open source tool that can be used by scientists (with or without a background in computational or mathematical modeling) to quantify key aspects of cell phenotypes (such as cell cycle and death parameters). Early applications of CellPD may include drug effect quantification, functional analysis of gene knockout experiments, data quality control, minable big data generation, and integration of biological data with computational models. PMID- 27655225 TI - Impact of Predicting Health Care Utilization Via Web Search Behavior: A Data Driven Analysis. AB - BACKGROUND: By recent estimates, the steady rise in health care costs has deprived more than 45 million Americans of health care services and has encouraged health care providers to better understand the key drivers of health care utilization from a population health management perspective. Prior studies suggest the feasibility of mining population-level patterns of health care resource utilization from observational analysis of Internet search logs; however, the utility of the endeavor to the various stakeholders in a health ecosystem remains unclear. OBJECTIVE: The aim was to carry out a closed-loop evaluation of the utility of health care use predictions using the conversion rates of advertisements that were displayed to the predicted future utilizers as a surrogate. The statistical models to predict the probability of user's future visit to a medical facility were built using effective predictors of health care resource utilization, extracted from a deidentified dataset of geotagged mobile Internet search logs representing searches made by users of the Baidu search engine between March 2015 and May 2015. METHODS: We inferred presence within the geofence of a medical facility from location and duration information from users' search logs and putatively assigned medical facility visit labels to qualifying search logs. We constructed a matrix of general, semantic, and location-based features from search logs of users that had 42 or more search days preceding a medical facility visit as well as from search logs of users that had no medical visits and trained statistical learners for predicting future medical visits. We then carried out a closed-loop evaluation of the utility of health care use predictions using the show conversion rates of advertisements displayed to the predicted future utilizers. In the context of behaviorally targeted advertising, wherein health care providers are interested in minimizing their cost per conversion, the association between show conversion rate and predicted utilization score, served as a surrogate measure of the model's utility. RESULTS: We obtained the highest area under the curve (0.796) in medical visit prediction with our random forests model and daywise features. Ablating feature categories one at a time showed that the model performance worsened the most when location features were dropped. An online evaluation in which advertisements were served to users who had a high predicted probability of a future medical visit showed a 3.96% increase in the show conversion rate. CONCLUSIONS: Results from our experiments done in a research setting suggest that it is possible to accurately predict future patient visits from geotagged mobile search logs. Results from the offline and online experiments on the utility of health utilization predictions suggest that such prediction can have utility for health care providers. PMID- 27655227 TI - Highlights of the Issue 10, 2016. PMID- 27655228 TI - Host response to fungal infections - how immunology and host genetics could help to identify and treat patients at risk. AB - In spite of the ever-increasing incidence and poor outcome of invasive fungal infections in immune compromised patients, there is currently no reliable method to accurately predict the risk, to monitor the outcome and to treat these infections. Protective immunity against Candida and Aspergillus depends on a highly coordinated interaction between the innate and adaptive immune systems. Genetic and immunological defects in components of these networks result in increased risk of invasive fungal infections among patients undergoing chemotherapy or transplant recipients. We review the most important genetic and immunological factors that influence human susceptibility to Candida and Aspergillus infections and discuss the potential role of basic research to promote precision medicine for infectious diseases. We discuss how immunogenetic studies can help to provide tools for improved identification of high-risk patients and the development of tailored antifungal therapies. PMID- 27655226 TI - Genomic prediction of coronary heart disease. AB - AIMS: Genetics plays an important role in coronary heart disease (CHD) but the clinical utility of genomic risk scores (GRSs) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear. Our aim was to construct and externally validate a CHD GRS, in terms of lifetime CHD risk and relative to traditional clinical risk scores. METHODS AND RESULTS: We generated a GRS of 49 310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested it using five prospective population cohorts (three FINRISK cohorts, combined n = 12 676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n = 3406, 587 incident CHD events). The GRS was associated with incident CHD (FINRISK HR = 1.74, 95% confidence interval (CI) 1.61-1.86 per S.D. of GRS; Framingham HR = 1.28, 95% CI 1.18-1.38), and was largely unchanged by adjustment for known risk factors, including family history. Integration of the GRS with the FRS or ACC/AHA13 scores improved the 10 years risk prediction (meta-analysis C-index: +1.5-1.6%, P < 0.001), particularly for individuals >=60 years old (meta-analysis C-index: +4.6-5.1%, P < 0.001). Importantly, the GRS captured substantially different trajectories of absolute risk, with men in the top 20% of attaining 10% cumulative CHD risk 12-18 y earlier than those in the bottom 20%. High genomic risk was partially compensated for by low systolic blood pressure, low cholesterol level, and non-smoking. CONCLUSIONS: A GRS based on a large number of SNPs improves CHD risk prediction and encodes different trajectories of lifetime risk not captured by traditional clinical risk scores. PMID- 27655229 TI - Online Work Force Analyzes Social Media to Identify Consequences of an Unplanned School Closure - Using Technology to Prepare for the Next Pandemic. AB - BACKGROUND: During an influenza pandemic, the United States Centers for Disease Control and Prevention (CDC) may recommend school closures. These closures could have unintended consequences for students and their families. Publicly available social media could be analyzed to identify the consequences of an unplanned school closure. METHODS: As a proxy for an unplanned, pandemic-related school closure, we used the district-wide school closure due to the September 10-18, 2012 teachers' strike in Chicago, Illinois. We captured social media posts about the school closure using the Radian6 social media-monitoring platform. An online workforce from Amazon Mechanical Turk categorized each post into one of two groups. The first group included relevant posts that described the impact of the closure on students and their families. The second group included irrelevant posts that described the political aspects of the strike or topics unrelated to the school closure. All relevant posts were further categorized as expressing a positive, negative, or neutral sentiment. We analyzed patterns of relevant posts and sentiment over time and compared our findings to household surveys conducted after other unplanned school closures. RESULTS: We captured 4,546 social media posts about the district-wide school closure using our search criteria. Of these, 930 (20%) were categorized as relevant by the online workforce. Of the relevant posts, 619 (67%) expressed a negative sentiment, 51 (5%) expressed a positive sentiment, and 260 (28%) were neutral. The number of relevant posts, and especially those with a negative sentiment, peaked on day 1 of the strike. Negative sentiment expressed concerns about childcare, missed school lunches, and the lack of class time for students. This was consistent with findings from previously conducted household surveys. CONCLUSION: Social media are publicly available and can readily provide information on the impact of an unplanned school closure on students and their families. Using social media to assess the impact of an unplanned school closure due to a public health event would be informative. An online workforce can effectively assist with the review process. PMID- 27655230 TI - Fast growth of well-aligned ZnO nanowire arrays by a microwave heating method and their photocatalytic properties. AB - The fast growth of aligned ZnO nanowire arrays with optimized structure is attractive for electrical and optical devices. In this paper, we report a controllable and rapid growth of ZnO nanowire arrays by a microwave-assisted hydrothermal method. When using different zinc salts as the precursors, the morphology of the samples changes a lot and the length growth rate is several times different. The growth mechanism is also investigated. It is found that the solution near neutral pH value is ideal for fast nanowire growth, in which the length of the nanowires increases linearly with growth time and the growth rate is over ten times faster than that in the traditional hydrothermal method. Therefore, aligned ZnO nanowire arrays can grow up to tens of microns in a few hours, while the density and sizes of these nanowires can be well controlled. The ZnO nanowire arrays used as photocatalysts present good photocatalytic performance to the degradation of methyl orange (MO) due to the large surface area. So this paper provides an effective method to obtain vertically aligned ZnO nanowire arrays for practical applications. PMID- 27655231 TI - Spatio-temporal heterogeneity of malaria vectors in northern Zambia: implications for vector control. AB - BACKGROUND: Despite large reductions in malaria burden across Zambia, some regions continue to experience extremely high malaria transmission. In Nchelenge District, Luapula Province, northern Zambia, almost half the human population carries parasites. Intervention coverage has increased substantially over the past decade, but comprehensive district-wide entomological studies to guide delivery of vector control measures are lacking. This study describes the bionomics and spatio-temporal patterns of malaria vectors in Nchelenge over a two and a half year period, investigates what household factors are associated with high vector densities and determines why vector control may not have been effective in the past to better guide future control efforts. METHODS: Between April 2012 and September 2014, twenty-seven households from across Nchelenge District were randomly selected for monthly light trap collections of mosquitoes. Anopheline mosquitoes were identified morphologically and molecularly to species. Foraging rates were estimated and sporozoite rates were determined by circumsporozoite ELISAs to calculate annual entomological inoculation rates. Blood feeding rates and host preference were determined by PCR. Zero-inflated negative binomial models measured environmental and household factors associated with mosquito abundance at study households such as season, proximity to the lake, and use of vector control measures. RESULTS: The dominant species in Nchelenge was An. funestus (s.s.) with An. gambiae (s.s.) as a secondary vector. Both vectors were found together in large numbers across the district and the combined EIRs of the two vectors exceeded 80 infectious bites per person per annum. An. funestus household densities increased in the dry season whilst An. gambiae surged during the rains. Presence of insecticide treated nets (ITNs) and closed eaves in the houses were found to be associated with fewer numbers of An. gambiae but not An. funestus. There was no association with indoor residual spraying (IRS). CONCLUSION: In Nchelenge, the co-existence of two highly anthropophagic vectors, present throughout the year, is likely to be driving the high malaria transmission evident in the district. The vectors here have been shown to be highly resistant to pyrethroids used for IRS during the study. Vector control interventions in this area would have to be multifaceted and district wide for effective control of malaria. PMID- 27655232 TI - Aerobic Exercise Improves Mood, Cognition, and Language Function in Parkinson's Disease: Results of a Controlled Study. AB - OBJECTIVES: Parkinson's disease (PD) results in a range of non-motor deficits that can affect mood, cognition, and language, and many of these issues are unresponsive to pharmacological intervention. Aerobic exercise can improve mood and cognition in healthy older adults, although only a few studies have examined exercise effects on these domains in PD. The current study assesses the effects of aerobic exercise on aspects of cognition, mood, and language production in people with PD. METHODS: This study compares the effects of aerobic exercise to stretch-balance training and a no-contact control group in participants with idiopathic PD. The aerobic and stretch-balance groups trained three times a week for 16 weeks, while controls continued normal activities. Outcome measures included disease severity, mood, cognition (speed of processing, memory, and executive function), and language production (picture descriptions). Cognition and language were assessed in single and dual task conditions. RESULTS: Depressive symptoms increased only in the control group (p<.02). Executive function improved in the aerobic exercise group only in the single task (p=.007) and declined in controls in the dual task. Completeness of picture descriptions improved significantly more in the aerobic group than in the stretch-balance group (p<.02). CONCLUSIONS: Aerobic exercise is a viable intervention for PD that can be protective against increased depressive symptoms, and can improve several non-motor domains, including executive dysfunction and related aspects of language production. (JINS, 2016, 22, 878-889). PMID- 27655233 TI - Beneficial effect of PEDF-transfected ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model. AB - Diabetes mellitus (DM) is an important risk factor for erectile dysfunction. Adipose-derived stem cells (ADSCs) are essential for maintaining erectile function but their function is impaired during hyperglycemia. To evaluate the effects of pigment epithelium-derived factor (PEDF)-transfected ADSCs on the restoration of erectile function ADSCs and PEDF-transfected ADSCs were exposed to normal or high glucose levels for 72 h and the effects on cell survival and protein expression were determined. For in vivo studies, rats with streptozocin induced DM were intravenously injected with ADSCs or PEDF-transfected ADSCs. Two weeks later, the intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured to assess erectile function, and penile tissues were harvested for further evaluation. PEDF overexpression in ADSCs protected cells against hyperglycemia-induced apoptosis (as determined by a TUNEL assay), increasing the expression of neurotrophic factors and decreasing the expression of inflammatory cytokines and oxidative stress-related proteins (as determined by western blotting and ELISA). In DM rats, transplantation with PEDF-transfected ADSCs effectively restored erectile function, as determined by the ICP/MAP ratio, compared with untreated ADSCs. PEDF overexpression also resulted in higher survival rates and decreased apoptosis of ADSCs. Promotion of neurotrophic factor expression and suppression of inflammatory cytokines and oxidative stress-related proteins were also observed after transplantation of PEDF-transfected ADSCs. Thus, our results demonstrate that transplantation of ADSCs restored erectile function in a rat model of DM, attenuating the negative effects of hyperglycemia. These findings indicate the therapeutic potential of ADSCs for treating erectile dysfunction and the additional benefits of PEDF overexpression. PMID- 27655234 TI - The Cost-Effectiveness of Two Forms of Case Management Compared to a Control Group for Persons with Dementia and Their Informal Caregivers from a Societal Perspective. AB - OBJECTIVES: The objective of this article was to compare the costs and cost effectiveness of the two most prominent types of case management in the Netherlands (intensive case management and linkage models) against no access to case management (control group) for people with already diagnosed dementia and their informal caregivers. METHODS: The economic evaluation was conducted from a societal perspective embedded within a two year prospective, observational, controlled, cohort study with 521 informal caregivers and community-dwelling persons with dementia. Case management provided within one care organization (intensive case management model, ICMM), case management where care was provided by different care organizations within one region (Linkage model, LM), and a group with no access to case management (control) were compared. The economic evaluation related incremental costs to incremental effects regarding neuropsychiatric symptoms (NPI), psychological health of the informal caregiver (GHQ-12), and quality adjusted life years (QALY) of the person with dementia and informal caregiver. RESULTS: Inverse-propensity-score-weighted models showed no significant differences in clinical or total cost outcomes between the three groups. Informal care costs were significantly lower in the ICMM group compared to both other groups. Day center costs were significantly lower in the ICMM group compared to the control group. For all outcomes, the probability that the ICMM was cost-effective in comparison with LM and the control group was larger than 0.97 at a threshold ratio of 0 ?/incremental unit of effect. CONCLUSION: This study provides preliminary evidence that the ICMM is cost-effective compared to the control group and the LM. However, the findings should be interpreted with caution since this study was not a randomized controlled trial. PMID- 27655236 TI - Caregiving Subgroups Differences in the Associations Between the Resilience Resources and Life Satisfaction. AB - Using a model of resilience, this study compared the direct and indirect associations between resilience resources (sense of mastery, openness to experience, emotion regulation, and social support) and life satisfaction among caregiving subgroups (spouses, adult-children, and parents). Participants were included from the survey of Midlife in the United States (MIDUS II). Estimates of direct and indirect relationships between the resources and life satisfaction were calculated for each subgroup, and differences in the relationships between subgroups were tested. The direct positive relationships between sense of mastery and life satisfaction were significant and stronger for spouses and parents than for adult-children. In contrast, an indirect relationship through social support between the two variables was stronger for adult-children than for spouses. Openness to experience had a direct positive link to life satisfaction among spouses, and emotion regulation was directly related to life satisfaction among parents. We suggested targeted interventions for caregiving subgroups. PMID- 27655235 TI - Clinical trial of modulatory effects of oxytocin treatment on higher-order social cognition in autism spectrum disorder: a randomized, placebo-controlled, double blind and crossover trial. AB - BACKGROUND: Autism spectrum disorders are neurodevelopmental conditions with severe impairments in social communication and interaction. Pioneering research suggests that oxytocin can improve motivation, cognition and attention to social cues in patients with autism spectrum disorder. The aim of this clinical trial is to characterize basic mechanisms of action of acute oxytocin treatment on neural levels and to relate these to changes in different levels of socio-affective and cognitive functioning. METHODS: This clinical study is a randomized, double blind, cross-over, placebo-controlled, multicenter functional magnetic resonance imaging study with two arms. A sample of 102 male autism spectrum disorder patients, diagnosed with Infantile Autistic Disorder (F84.0 according to ICD-10), Asperger Syndrome (F84.5 according to ICD-10), or Atypical Autism (F84.1 according to ICD-10) will be recruited and will receive oxytocin and placebo nasal spray on two different days. Autism spectrum disorder patients will be randomized to determine who receives oxytocin on the first and who on the second visit. Healthy control participants will be recruited and case-control matched to the autism spectrum disorder patients. The primary outcome will be neural network activity, measured with functional magnetic resonance imaging while participants perform socio-affective and -cognitive tasks. Behavioral markers such as theory of mind accuracy ratings and response times will be assessed as secondary outcomes in addition to physiological measures such as skin conductance. Trait measures for alexithymia, interpersonal reactivity, and social anxiety will also be evaluated. Additionally, we will analyze the effect of oxytocin receptor gene variants and how these potentially influence the primary and secondary outcome measures. Functional magnetic resonance imaging assessments will take place at two time points which will be scheduled at least two weeks apart to ensure a sufficient wash-out time after oxytocin treatment. The study has been approved by an ethical review board and the competent authority. DISCUSSION: Revealing the mechanisms of acute oxytocin administration, especially on the socio-affective and -cognitive domains at hand, will be a further step towards novel therapeutic interventions regarding autism. TRIAL REGISTRATION: German Clinical Trial Register DRKS00010053 . The trial was registered on the 8th of April 2016. PMID- 27655237 TI - Seniors Online: Attitudes Toward the Internet and Coping With Everyday Life. AB - Many older people do not use the Internet. We investigated the attitudes of older people who do (onliners) or do not (offliners) use the Internet, to assess their views of the Internet and whether they see the Internet as a resource for coping with everyday life situations. Participants aged >=65 years ( N = 1,037), living in Switzerland, were interviewed in a telephone survey. Descriptive and multivariate analyses were conducted. The data show (a) many of the respondents viewed the Internet as useful, in general, and for coping with everyday life situations; (b) onliners saw more positive aspects of the Internet than did offliners; and PMID- 27655238 TI - Long-term Follow-up After Ileorectal Anastomosis for Ulcerative Colitis: A GETAID/GETAID Chirurgie Multicenter Retrospective Cohort of 343 Patients. AB - OBJECTIVES: To determine the cumulative incidence and the prognostic factors of ileorectal anastomosis (IRA) failure after colectomy for ulcerative colitis (UC). BACKGROUND: Although ileal pouch-anal anastomosis is recommended after colectomy for UC, IRA is still performed. METHODS: This was a multicenter retrospective cohort study, which included patients with IRA for UC performed between 1960 and 2014. IRA failure was defined as secondary proctectomy and/or rectal cancer occurrence. Uni- and multivariate survival analyses were performed using Cox proportional hazards models. RESULTS: A total of 343 patients from 13 French centers were included. Median follow up after IRA was 10.6 years. IRA failure rates were estimated at 27.0% (95% confidence interval, CI, 22-32) and 40.0% (95% CI 33-47) at 10 and 20 years, respectively. Median survival time without IRA failure was estimated at 26.8 years. Two thirds of secondary proctectomies were performed for refractory proctitis, and 20% for rectal neoplasia. Univariate analysis identified factors associated with IRA failure: IRA performed after 2005, a longer duration of disease at the time of IRA, indication for colectomy and having received immunomodulative agents before IRA. In multivariate analysis, treatment with both immunosuppressant (IS) and anti-TNF before colectomy was independently associated with IRA failure (HR=2.9, 95% CI 1.2-7.1). Conversely, colectomy for severe acute colitis was associated with decreased risk of IRA failure (HR=0.6, 95% CI 0.4-0.97). DISCUSSION: Patients with UC have a high risk of IRA failure, particularly when colectomy is performed for refractory disease. However, IRA could be discussed after colectomy for severe acute colitis, or in patients naive to IS and anti-TNF. PMID- 27655239 TI - Carolinas Comfort Scale as a Measure of Hernia Repair Quality of Life: A Reappraisal Utilizing 3788 International Patients. AB - OBJECTIVE: The goal of the present study was to reaffirm the psychometric properties of the CCS using an expansive, multinational cohort. BACKGROUND: The Carolinas Comfort Scale (CCS) is a validated, disease-specific, quality of life (QOL) questionnaire developed for patients undergoing hernia repair. METHODS: The data were obtained from the International Hernia Mesh Registry, an American, European, and Australian prospective, hernia repair database designed to capture information delineating patient demographics, surgical findings, and QOL using the CCS at 1, 6, 12, and 24 months postoperatively. RESULTS: A total of 3788 patients performed 11,060 postoperative surveys. Patient response rates exceeded 80% at 1 year postoperatively. Acceptability was demonstrated by an average of less than 2 missing items per survey. The formal test of reliability revealed a global Cronbach's alpha exceeding 0.95 for all hernia types. Test-retest validity was supported by the correlation found between 2 different administrations of the CCS using the kappa coefficient. Principal component analysis identified 2 components with a good distribution of variance, with the first component explaining approximately 60% of the variance, regardless of hernia type. Discriminant validity was assessed by comparing survey responses and use of pain medication at 1 month postoperatively and analysis revealed that symptomatic patients demonstrated significantly higher odds of requiring pain medication in all activity domains and for all hernia types. CONCLUSIONS: The present study confirms that the CCS questionnaire is a validated, sensitive, and robust instrument for assessing QOL after hernia repair, which has become a predominant outcome measure in this discipline of surgery. PMID- 27655240 TI - Frailty, Length of Stay, and Mortality in Kidney Transplant Recipients: A National Registry and Prospective Cohort Study. AB - OBJECTIVE: To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. BACKGROUND: Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. METHODS: We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS >=2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). RESULTS: Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS >=2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). CONCLUSIONS: Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS. PMID- 27655241 TI - Rescuing the Clinical Breast Examination: Advances in Classifying Technique and Assessing Physician Competency. AB - OBJECTIVE: Develop new performance evaluation standards for the clinical breast examination (CBE). SUMMARY BACKGROUND DATA: There are several, technical aspects of a proper CBE. Our recent work discovered a significant, linear relationship between palpation force and CBE accuracy. This article investigates the relationship between other technical aspects of the CBE and accuracy. METHODS: This performance assessment study involved data collection from physicians (n = 553) attending 3 different clinical meetings between 2013 and 2014: American Society of Breast Surgeons, American Academy of Family Physicians, and American College of Obstetricians and Gynecologists. Four, previously validated, sensor enabled breast models were used for clinical skills assessment. Models A and B had solitary, superficial, 2 cm and 1 cm soft masses, respectively. Models C and D had solitary, deep, 2 cm hard and moderately firm masses, respectively. Finger movements (search technique) from 1137 CBE video recordings were independently classified by 2 observers. Final classifications were compared with CBE accuracy. RESULTS: Accuracy rates were model A = 99.6%, model B = 89.7%, model C = 75%, and model D = 60%. Final classification categories for search technique included rubbing movement, vertical movement, piano fingers, and other. Interrater reliability was (k = 0.79). Rubbing movement was 4 times more likely to yield an accurate assessment (odds ratio 3.81, P < 0.001) compared with vertical movement and piano fingers. Piano fingers had the highest failure rate (36.5%). Regression analysis of search pattern, search technique, palpation force, examination time, and 6 demographic variables, revealed that search technique independently and significantly affected CBE accuracy (P < 0.001). CONCLUSIONS: Our results support measurement and classification of CBE techniques and provide the foundation for a new paradigm in teaching and assessing hands-on clinical skills. The newly described piano fingers palpation technique was noted to have unusually high failure rates. Medical educators should be aware of the potential differences in effectiveness for various CBE techniques. PMID- 27655242 TI - Serogenotyping and emergence of extended-spectrum beta-lactamase genes in non typhoidal Salmonella: first report from Saudi Arabia. PMID- 27655243 TI - Effects of Different Levels of Calcium Intake on Brain Cell Apoptosis in Fluorosis Rat Offspring and Its Molecular Mechanism. AB - The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague-Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3 months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells. PMID- 27655245 TI - Mobile Sensing and Support for People With Depression: A Pilot Trial in the Wild. AB - BACKGROUND: Depression is a burdensome, recurring mental health disorder with high prevalence. Even in developed countries, patients have to wait for several months to receive treatment. In many parts of the world there is only one mental health professional for over 200 people. Smartphones are ubiquitous and have a large complement of sensors that can potentially be useful in monitoring behavioral patterns that might be indicative of depressive symptoms and providing context-sensitive intervention support. OBJECTIVE: The objective of this study is 2-fold, first to explore the detection of daily-life behavior based on sensor information to identify subjects with a clinically meaningful depression level, second to explore the potential of context sensitive intervention delivery to provide in-situ support for people with depressive symptoms. METHODS: A total of 126 adults (age 20-57) were recruited to use the smartphone app Mobile Sensing and Support (MOSS), collecting context-sensitive sensor information and providing just-in-time interventions derived from cognitive behavior therapy. Real-time learning-systems were deployed to adapt to each subject's preferences to optimize recommendations with respect to time, location, and personal preference. Biweekly, participants were asked to complete a self-reported depression survey (PHQ-9) to track symptom progression. Wilcoxon tests were conducted to compare scores before and after intervention. Correlation analysis was used to test the relationship between adherence and change in PHQ-9. One hundred twenty features were constructed based on smartphone usage and sensors including accelerometer, Wifi, and global positioning systems (GPS). Machine-learning models used these features to infer behavior and context for PHQ-9 level prediction and tailored intervention delivery. RESULTS: A total of 36 subjects used MOSS for >=2 weeks. For subjects with clinical depression (PHQ-9>=11) at baseline and adherence >=8 weeks (n=12), a significant drop in PHQ-9 was observed (P=.01). This group showed a negative trend between adherence and change in PHQ-9 scores (rho=-.498, P=.099). Binary classification performance for biweekly PHQ-9 samples (n=143), with a cutoff of PHQ-9>=11, based on Random Forest and Support Vector Machine leave-one-out cross validation resulted in 60.1% and 59.1% accuracy, respectively. CONCLUSIONS: Proxies for social and physical behavior derived from smartphone sensor data was successfully deployed to deliver context-sensitive and personalized interventions to people with depressive symptoms. Subjects who used the app for an extended period of time showed significant reduction in self reported symptom severity. Nonlinear classification models trained on features extracted from smartphone sensor data including Wifi, accelerometer, GPS, and phone use, demonstrated a proof of concept for the detection of depression superior to random classification. While findings of effectiveness must be reproduced in a RCT to proof causation, they pave the way for a new generation of digital health interventions leveraging smartphone sensors to provide context sensitive information for in-situ support and unobtrusive monitoring of critical mental health states. PMID- 27655244 TI - Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. AB - BACKGROUND: While mortality in the United States has decreased for most cancers, mortality from combined hepatocellular liver cancer and intrahepatic cholangiocarcinoma (ICC) has increased and ranked 1st in annual percent increase among cancer sites. Because reported statistics combine ICC with other liver cancers, mortality rates of cholangiocarcinoma (CCA) remain unknown. This study is to determine CCA mortality trends and variation based on national data. METHODS: This nation-wide study was based on the underlying cause of death data collected by the National Center for Health Statistics (NCHS) between 1999 and 2014. The Center for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) system was used to obtain data. ICC and extra hepatic CCA (ECC) were defined by ICD-10 diagnosis codes. Age-adjusted mortality rate was standardized to the US population in 2000. RESULTS: There were more than 7000 CCA deaths each year in the US after 2013. CCA mortality for those aged 25+ increased 36 % between 1999 and 2014, from 2.2 per 100,000 (95 % confidence interval [CI] 2.1-2.3) to 3.0 per 100,000 (95 % CI, 2.9-3.1). Mortality rates were lower among females compared with males (risk ratio [RR] 0.78, 95 % CI 0.77 0.79). Asians had the highest mortality. Between 2004 and 2014, the increase in CCA mortality was highest among African Americans (45 %) followed by Asians (22 %), and whites (20 %). CONCLUSION: Based on the most recent national data, CCA mortality rates have increased substantially in the past decade. Among different race/ethnic groups, African Americans have the highest increase in CCA mortality. PMID- 27655246 TI - Probiotic Enterococcus faecalis Symbioflor(r) down regulates virulence genes of EHEC in vitro and decrease pathogenicity in a Caenorhabditis elegans model. AB - Enterohemorrhagic E. coli O157:H7 (EHEC) shorten the lifespan of Caenorhabditis elegans compared to avirulent bacteria. Co-feeding EHEC with Enterococcus faecalis Symbioflor(r) significantly increased the worms' lifespan. The transcriptome of EHEC grown in vitro with or without Symbioflor(r) was analyzed using RNA-seq. The analysis revealed downregulation of several virulence associated genes in the presence of Symbioflor(r), including virulence key genes (e.g., LEE, flagellum, quorum-sensing). The downregulation of the LEE genes was corroborated by lux-transposon mutants. Upregulated genes included acid response genes, due to a decrease in pH exerted by Symbioflor(r). Further genes indicate cellular stress in EHEC (e.g. prophage/mobile elements involved in excision, cell lysis, and cell division inhibition). Thus, the observed protection of C. elegans during an EHEC infection by the probiotic Symbioflor(r) is suggested to be caused by triggering concomitant transcriptomic changes. To verify the biological relevance of this modulation, exemplary genes found to be influenced by Symbioflor(r) were knocked out (fliD, espB, Z3136, Z3917, and L7052). The lifespan of nematodes changed when using knock-outs as food source and the effect could be complemented in trans. In summary, Symbioflor(r) appears to be a protective probiotic in the nematode model. PMID- 27655247 TI - Short-Term Perinatal Outcome among Term Infants with Prenatal Diagnosis of Large Abdominal Circumference. AB - Background Measuring fetal abdominal circumference (AC) prenatally is an effective tool for predicting neonatal weight and macrosomia. Data are lacking regarding the outcome of newborn infants with prenatal diagnosis of large AC. Aim The aim of this study was to evaluate early short-term neonatal outcome among term singleton newborn infants with prenatal diagnosis of large AC. Methods Retrospective data were collected on 501 term infants with prenatal diagnosis of large AC (>= 360 mm) and on matched controls, including information on maternal condition and on infant perinatal complications. Results In compare with controls, the study group had higher incidence of macrosomia (188 [37.5%] vs. 18 [3.6%], p < 0.001), hypoglycemia (48 (9.6%) vs. 25 [5%], p = 0.007), and significant morbidity (49 [9.8%] vs. 28 [5.6%], p = 0.017) but without increased incidence of congenital malformations or other perinatal complications. Only among the macrosomic, study subgroup and their controls differences were recorded including hypoglycemia (17.6 vs. 4.8%, p < 0.001), need for oral glucose (11.2 vs. 2.7%, p = 0.002), significant morbidity (10.1 vs. 3.7%, p = 0.024), and hospitalization in special care unit (11.7 vs. 4.3%, p = 0.012). Conclusion Prelabor diagnosis of large AC mostly reflects the infant's high birth weight and macrosomia with the associated perinatal complications. Large AC by itself was not predictive of any congenital malformations or perinatal and postnatal complications. PMID- 27655248 TI - All-fiber transparent piezoelectric harvester with a cooperatively enhanced structure. AB - In this paper, we demonstrated a highly-flexible all-fiber based transparent piezoelectric harvester (ATPH) by using the direct-write, near-field electrospinning (NFES) technique and polyvinylidene fluoride (PVDF) micro/nano fibers (MNFs) as source materials. Here, we comprehensively show that transferred high performance transparent electrodes with Au-coated nanowire (NW) electrodes can be obtained using a facile and scalable combined fabrication route of both electrospinning and sputtering processes. Au-coated MNFs of a.c. 110 nm thick can significantly reduce junction resistance, which results in high transmittance (90%) at low sheet resistance (175 Omega sq(-1)). The Au-coated MNFs electrodes also show great flexibility and stretchability, which easily surpass the brittleness of indium tin oxide (ITO) films. Further improvement in ATPH performance was realized by rolling the device into a cylindrical shape, resulting in an increase in power output due to the cooperatively enhanced effect. The rolled ATPH with 0.34 cm diameter produces a high output voltage of ~4.1 V, current ~295 nA at a strain of 0.5% and 5 hz. This can efficiently run commercially available electronic components in a self-powered mode without any external electrical supply. PMID- 27655249 TI - When smokers quit: exposure to nicotine and carcinogens persists from thirdhand smoke pollution. AB - BACKGROUND: Over a 6-month period, we examined tobacco smoke pollutants (also known as thirdhand smoke, THS) that remained in the homes of former smokers and the exposure to these pollutants. METHODS: 90 smokers completed study measures at baseline (BL). Measures were repeated among verified quitters 1 week (W1), 1 month (M1), 3 months (M3) and 6 months (M6) following cessation. Measures were analysed for THS pollutants on household surfaces, fingers and in dust (ie, nicotine, tobacco-specific nitrosamines) and for urinary markers of exposure (ie, cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)). RESULTS: We observed significant short-term reduction of nicotine on surfaces (BL: 22.2 MUg/m2, W1: 10.8 MUg/m2) and on fingers of non-smoking residents (BL: 29.1 ng/wipe, W1: 9.1 ng/wipe) without further significant changes. Concentrations of nicotine and nicotine-derived nitrosamine ketone (NNK) in dust did not change and remained near BL levels after cessation. Dust nicotine and NNK loadings significantly increased immediately following cessation (nicotine BL: 5.0 MUg/m2, W1: 9.3 MUg/m2; NNK BL: 11.6 ng/m2, W1: 36.3 ng/m2) before returning to and remaining at near BL levels. Cotinine and NNAL showed significant initial declines (cotinine BL: 4.6 ng/mL, W1: 1.3 ng/mL; NNAL BL: 10.0 pg/mL, W1: 4.2 pg/mL) without further significant changes. CONCLUSIONS: Homes of smokers remained polluted with THS for up to 6 months after cessation. Residents continued to be exposed to THS toxicants that accumulated in settled house dust and on surfaces before smoking cessation. Further research is needed to better understand the consequences of continued THS exposure after cessation and the efforts necessary to remove THS. PMID- 27655250 TI - Analyzing Confabulations in Schizophrenia and Healthy Participants. AB - OBJECTIVES: Confabulations occur in schizophrenia and certain severe neuropsychiatric conditions, and to a lesser degree in healthy individuals. The present study used a forced confabulation paradigm to assess differences in confabulation between schizophrenia patients and healthy controls. METHODS: Schizophrenia patients (n=60) and healthy control participants (n=19) were shown a video with missing segments, asked to fill in the gaps with speculations, and tested on their memory for the story. Cognitive functions and severity of symptoms were also evaluated. RESULTS: Schizophrenia patients generated significantly more confabulations than healthy control participants and had a greater tendency to generate confabulations that were related to each other. Schizophrenic confabulations were positively associated with temporal context confusions and formal thought disorder, and negatively with delusions. CONCLUSIONS: Our findings show that the schizophrenia patients generate more confabulations than healthy controls and schizophrenic confabulations are associated with positive symptoms. (JINS, 2016, 22, 911-919). PMID- 27655251 TI - Micropropagation of transgenic lettuce containing HBsAg as a method of mass-scale production of standardised plant material for biofarming purposes. AB - KEY MESSAGE: Micropropagation protocol of transgenic lettuce bearing S-, M- and L HBsAg was developed for increased production of uniformised material for oral vaccine preparation. Effective manufacturing of plant-based biopharmaceuticals, including oral vaccines, depends on sufficient content of a protein of interest in the initial material and its efficient conversion into an administrable formulation. However, stable production of plants with a uniformised antigen content is equally important for reproducible processing. This can be provided by micropropagation techniques. Here, we present a protocol for micropropagation of transgenic lettuce lines bearing HBV surface antigens: S-, M- and L-HBsAg. These were multiplied through axillary buds to avoid the risk of somaclonal variation. Micropropagation effectiveness reached 3.5-5.7 per passage, which implies potential production of up to 6600 plant clones within a maximum 5 months. Multiplication and rooting rates were statistically homogenous for most transgenic and control plants. For most lines, more than 90 % of clones obtained via in vitro micropropagation had HBsAg content as high as reference plants directly developed from seeds. Clones were also several times more uniform in HBsAg expression. Variation coefficients of HBsAg content did not exceed 10 % for approximately 40-85 % of clones, or reached a maximum 20 % for 90 % of all clones. Tissue culture did not affect total and leaf biomass yields. Seed production for clones was decreased insignificantly and did not impact progeny condition. Micropropagation facilitates a substantial increase in the production of lettuce plants with high and considerably equalised HBsAg contents. This, together with the previously reported optimisation of plant tissue processing and its long-term stability, constitutes a successive step in manufacturing of a standardised anti-HBV oral vaccine of reliable efficacy. PMID- 27655253 TI - Major Depression and Long-Term Outcomes of Acute Kidney Injury. AB - BACKGROUND: The prevalence of depression and its relationship to poor outcomes in chronic kidney disease are established facts. Such prognostic impact in acute kidney injury (AKI) is not known. This study determines the prognostic implication of a diagnosis of depression on renal recovery and major adverse cardiovascular events (MACE), a new diagnosis of myocardial infarction, cerebrovascular disease (CVD, stroke or transient ischemic attack) or congestive heart failure (CHF) after hospitalization with AKI. METHODS: The study population comprises adults admitted to the University of Virginia Medical Center between January 1, 2002 and December 31, 2012 who suffered AKI during admission. Long term outcomes, MACE and all-cause mortality, were compared between 2 groups; patients with preexisting diagnosis of major depression and those without. Risk adjusted multivariable Cox proportional hazards regression examined the association between major depression and these outcomes. RESULTS: Patients with AKI numbering 11,425 survived beyond 90 days and had data available. Of these patients, 2,519 (22%) were majorly affected by depression; more often, younger patients, females, African Americans, and those with more comorbid conditions, especially CHF, CVD, diabetes, peptic ulcer disease, chronic pulmonary disease and liver disease were found to be affected with depression. Crude hazard ratio for MACE was 1.245, 95% CI 1.150-1.348 and for all-cause mortality 1.186, 95% CI 1.091-1.290; p < 0.001, that is, the cohort with major depression had a long-term risk for MACE and all-cause mortality increased by 24 and 18%, respectively. CONCLUSION: Patients who develop AKI in hospital and have preexisting major depression are at greater long-term risk of MACE and all-cause mortality. PMID- 27655252 TI - Pancreas-sparing total duodenectomy for Spigelman stage IV duodenal polyposis associated with familial adenomatous polyposis: experience of 10 cases at a single institution. AB - Duodenal cancer is a leading cause of death in patients with familial adenomatous polyposis (FAP). In patients with Spigelman's classification (SC) stage IV duodenal polyposis (DP), careful endoscopic surveillance by specialists or surgical intervention is mandatory. We herein report the surgical and pathological outcomes of FAP patients with SC stage duodenal polyposis undergoing pancreas-sparing total duodenectomy (PSTD), which has been rarely reported but seems optimal in such patients. PSTD and distal gastrectomy with Billroth-I type reconstruction in ten consecutive FAP patients with SC stage IV DP are reported. The median duration of surgery was 396 min (range 314-571 min) and the median estimated blood loss was 480 mL (range 100-975 mL). Significant postoperative complications included wound infection in 1 patient, pancreatic fistula [International Study Group on Pancreatic Fistula definition (ISGPF) grade B] in 4 patients. Histopathologic examinations revealed a well-differentiated carcinoma in situ in 3 patients and others were all adenomas. Over a median follow-up period of 15 months (range 9-29 months), 1 patient developed a stomal ulcer which improved with medical treatment. There were no patients with a body weight loss of >=10 % relative to the preoperative body weight. No recurrence were experienced during the follow up period. Patients were free from postoperative diabetes mellitus. PSTD is a feasible and acceptable procedure in FAP patients with SC stage IV DP, in terms of surgical, pathological and clinical outcome. However, accumulation of the patients and long-term follow up study is necessary. PMID- 27655255 TI - Consequences of a Chronic Exposure of Cultured Brain Astrocytes to the Anti Retroviral Drug Efavirenz and its Primary Metabolite 8-Hydroxy Efavirenz. AB - Efavirenz is a widely prescribed non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infections. To test for potential long-term consequences of efavirenz on brain cells, cultured primary astrocytes were incubated with this substance or with its primary metabolite 8-hydroxy efavirenz for up to 7 days. Both, efavirenz and 8-hydroxy efavirenz caused time- and concentration-dependent cell toxicity and stimulated in subtoxic concentrations the glycolytic flux (glucose consumption and lactate release) in astrocytes. As 8-hydroxy efavirenz was less toxic than efavirenz and stimulated glycolysis in lower concentrations we tested for a potential hydroxylation of efavirenz to 8-hydroxy efavirenz in astrocytes. Analysis of media and cell lysates by HPLC-UV and mass spectrometry revealed that after 3 days of incubation viable astrocytes had accumulated about 17 and 7 % of the applied efavirenz and 8-hydroxy efavirenz, respectively. However, in cultures treated with efavirenz neither 8-hydroxy efavirenz nor any other known metabolite of efavirenz was detectable. These data demonstrate that cultured rat astrocytes efficiently accumulate, but not metabolize, efavirenz and 8-hydroxy efavirenz and that the observed chronic stimulation of glycolysis is mediated by both efavirenz and 8-hydroxy efavirenz. PMID- 27655254 TI - Ammonia Attenuates LPS-Induced Upregulation of Pro-Inflammatory Cytokine mRNA in Co-Cultured Astrocytes and Microglia. AB - Hepatic encephalopathy (HE) is associated with cerebral microglia activation. Ammonia, a major toxin of HE, activates microglia in vitro but does not trigger pro-inflammatory cytokine synthesis. In the present study we analysed effects of ammonia on lipopolysaccharide (LPS)-induced upregulation of microglia activation and cytokine mRNA as well as on cytokine secretion in mono-cultured microglia and co-cultured astrocytes and microglia. In mono-cultured microglia LPS (100 ng/ml, 18 h) strongly elevated mRNA levels of the microglia activation marker CD14 and the pro-inflammatory cytokines IL-1alpha/beta, IL-6 and TNF-alpha. NH4Cl (5 mmol/l) had no effect on LPS-induced upregulation of CD14, IL-1alpha/beta and IL 6 mRNA but enhanced LPS-induced upregulation of TNF-alpha mRNA in mono-cultured microglia. In co-cultured astrocytes and microglia, however, LPS-induced upregulation of IL-1alpha/beta, TNF-alpha, IL-6, CD14 but not of IL-10, IL-12A/B or TGFbeta1-3 mRNA was attenuated by NH4Cl. LPS-induced upregulation of IL 1alpha/beta, IL-6 and TNF-alpha was also diminished by the TGR5-ligands allopregnanolone and taurolithocholic acid in mono-cultured microglia. NH4Cl also attenuated LPS-induced release of MCP-1, IL-6 and IL-10 in mono-cultured microglia. mRNA level of surrogate marker for microglia activation (CD14) and for the anti-inflammatory M2-type microglia (CD163, CXCL1, CXCL2) were also elevated in post mortem brain tissue taken from the fusiforme gyrus of patients with liver cirrhosis and HE. The findings suggest that ammonia attenuates LPS-induced microglia reactivity in an astrocyte-dependent way. One may speculate that these anti-inflammatory effects of ammonia may be triggered by neurosteroids derived from astrocytes and may account for absence of microglia reactivity in cerebral cortex of cirrhotic patients with HE. PMID- 27655257 TI - Heart failure in a neonate with multiple cardiac masses. AB - CLINICAL INTRODUCTION: A 16-day-old male neonate weighing 3.4 kg presented with severe heart failure. His heart rate was 190/min, normal sinus rhythm, blood pressure was 55/30 mm Hg and respiratory rate was 65/min. Transthoracic echocardiography and cardiac MRI showed multiple intracardiac masses; the largest was filling most of the left ventricular cavity (figure 1A) (see online supplementary video 1 and figure S1), measuring around 2.8 cm*1.8 cm and arising from the apical septum. Left ventricular function was moderately impaired with an ejection fraction of 40%. Due to accelerated haemodynamic instability, the mass was excised surgically. Through left ventriculotomy, a large mass could be identified which was attached with a pedicle to the apical septum. This mass was excised with its pedicle.During early postoperative course, the patient developed subdural and intraventricular haemorrhage, necessitating insertion of a ventriculoperitoneal shunt. MRI of the brain showed dark-signalled subependymal nodules and multiple cortical patches of high T2 signals (see online supplementary figure S2). The patient had no neurological sequelae and was discharged home.The patient was discharged home with no neurological sequelae. During the 2-year follow-up period, serial echocardiograms showed regression of the rest of the cardiac tumours and improvement of cardiac functions (see online supplementary figure S3). However, fibrous plaques were observed on the child's forehead. QUESTION: What is the most likely diagnosis? HibernomaFibromaRhabdomyomaRhabdomyosarcoma. PMID- 27655256 TI - Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats. AB - Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1beta (IL-1beta) and Interleukin -17A (IL 17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP. PMID- 27655258 TI - One-year visual outcome of small incision lenticule extraction (SMILE) surgery in high myopic eyes: retrospective cohort study. AB - OBJECTIVE: To determine whether the long-term visual outcome of small incision lenticule extraction (SMILE) surgery is consistent with the short-term results in high myopic eyes. DESIGN: Retrospective cohort study; data collected from 8 August 2011 to 31 August 2015. SETTING: Single refractive surgery centre. PARTICIPANTS: A total of 156 eyes were studied: 65 eyes of 39 subjects (22 female/17 male) in the high myopic group (manifest refraction spherical equivalent (MRSE) >=-6.0 D), and 91 eyes of 54 subjects (29 female/25 male) in the control group (MRSE <-6.0 D). The inclusion criteria were subjects who had follow-ups after 1 day, 1 week, 1 month, 3, 6 months and 1 year with the manifest refraction, uncorrected and corrected distance visual acuity (UDVA/CDVA). There were no statistically significant differences between the two groups in the subjects' gender, age, or cylindrical dioptre, preoperatively (p=0.835, p=0.055, p=0.341, respectively). PRIMARY AND SECONDARY OUTCOME MEASURES: UDVA, refractive stability, safety index (postoperative CDVA/preoperative CDVA), and predictability (the percentage of eyes within +/-0.50 D). RESULTS: In both groups, the 1-year UDVA and safety index were significantly better than results at 1 day (high myopic group: p=0.035, p<0.001; control group: p<0.016, p<0.001); the 1-year predictability showed no significant difference with the short-term results (p=1.00 in both groups). In the high myopic eyes, the 1-year MRSE was significantly worse than the short-term result (p=0.048). To correct it, the added magnitude (D) for the high myopic eyes may equal 0.13*Attempted SE (D)-0.66 D. However, the postoperative MRSE showed no differences from 1 day to 1 year (p=0.612) in the control group. CONCLUSIONS: The 1-year visual outcomes were better than the short-term results after the SMILE surgery on the visual acuity and safety. However, the high myopic eyes suffered a significant regression at 1 year, which may be corrected by adding additional magnitude to the SE for high myopic eyes. PMID- 27655259 TI - A comparison of pregnancy outcomes in Ghanaian women with varying dietary diversity: a prospective cohort study protocol. AB - INTRODUCTION: Poor dietary intake during pregnancy can have negative repercussions on the mother and fetus. This study therefore aims to explore the dietary diversity (DD) of pregnant women and its associations with pregnancy outcomes among women in Northern Ghana. The main outcome variables to be measured are gestational weight gain and birth weight. METHODS AND ANALYSIS: A prospective cohort study design will be used and 600 pregnant women in their first trimester will be systematically recruited at health facilities and followed until delivery. In three follow-up visits after recruitment, information on sociodemographic and general characteristics, physical activity (International Physical Activity Questionnaire (IPAQ) short form, dietary intake (24-hour food recall), anthropometry and pregnancy outcomes will be collected. DD will be measured three times using the minimum DD-women (MDD-W) indicator and the mean of the three values overall will be used to determine low (<5 food groups) and high (>=5 food groups) DD. Data will be analysed using SPSS. Comparisons between groups (categorical data) will be made using the chi2 test for proportions, and t tests and ANOVA will be performed on continuous variables. Regression analysis will be used to identify independent outcome predictors while controlling for possible confounding factors. The results may help to identify differences in DD between healthy and unhealthy pregnancy outcomes. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee of Tehran University of Medical Sciences and the ethical review committee of the Tamale Teaching Hospital. Written informed consent will be obtained from all subjects. The results will be published in due course. PMID- 27655260 TI - Ability of preoperative falls to predict postsurgical outcomes in non-selected patients undergoing elective surgery at an academic medical centre: protocol for a prospective cohort study. AB - INTRODUCTION: Falls are increasingly recognised for their ability to herald impending health decline. Despite the likely susceptibility of postsurgical patients to falls, a detailed description of postoperative falls in an unselected surgical population has never been performed. One study suggests that preoperative falls may forecast postoperative complications. However, a larger study with non-selected surgical patients and patient-centred outcomes is needed to provide the generalisability and justification necessary to implement preoperative falls assessment into routine clinical practice. The aims of this study are therefore twofold. First, we aim to describe the main features of postoperative falls in a population of unselected surgical patients. Second, we aim to test the hypothesis that a history of falls in the 6 months prior to surgery predicts postoperative falls, poor quality of life, functional dependence, complications and readmission. METHODS AND ANALYSIS: To achieve these goals, we study adult patients who underwent elective surgery at our academic medical centre and were recruited to participate in a prospective, survey-based cohort study called Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) (NCT02032030). Patients who reported falling in the 6 months prior to surgery will be considered 'exposed.' The primary outcome of interest is postoperative falls within 30 days of surgery. Secondary outcomes include postoperative functional dependence, quality of life (both physical and mental), in-hospital complications and readmission. Regression models will permit controlling for important confounders. ETHICS AND DISSEMINATION: The home institution's Institutional Review Board approved this study (IRB ID number 201505035). The authors will publish the findings, regardless of the results. PMID- 27655261 TI - Discontinuing financial incentives for adherence to antipsychotic depot medication: long-term outcomes of a cluster randomised controlled trial. AB - OBJECTIVES: In a cluster randomised controlled trial, offering financial incentives improved adherence to antipsychotic depot medication over a 1-year period. Yet, it is unknown whether this positive effect is sustained once the incentives stop. METHODS AND ANALYSES: Patients in the intervention and control group were followed up for 2 years after the intervention. Primary and secondary outcomes were assessed at 6 months and 24 months post intervention. Assessments were conducted between September 2011 and November 2014. RESULTS: After the intervention period, intervention and control groups did not show any statistically significant differences in adherence, neither in the first 6 months (71% and 77%, respectively) nor in the following 18 months (68%, 74%). There were no statistically significant differences in secondary outcomes, that is, adherence >=95% and untoward incidents either. CONCLUSIONS: It may be concluded that incentives to improve adherence to antipsychotic maintenance medication are effective only for as long as they are provided. Once they are stopped, adherence returns to approximately baseline level with no sustained benefit. TRIAL REGISTRATION NUMBER: ISRCTN77769281; Results. PMID- 27655262 TI - Sodium intake and blood pressure in children and adolescents: protocol for a systematic review and meta-analysis. AB - INTRODUCTION: Hypertension is a major risk factor for cardiovascular diseases. In adults, high sodium intake is associated with elevated blood pressure. In children, experimental studies have shown that reducing sodium intake can reduce blood pressure. However, their external validity is limited, notably because the sodium reduction was substantial and not applicable in a real-life setting. Observational studies, on the other hand, allow assess the association between blood pressure and sodium intake across usual levels of consumption. There is also evidence that the association differs between subgroups of children according to age and body weight. Our objective is to conduct a systematic review and meta-analysis of experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents and to assess whether the association differs according to age and body weight. METHODS AND ANALYSIS: A systematic search of the MEDLINE, EMBASE, CINAHL and CENTRAL databases will be conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age will be included. The exposure will be dietary sodium intake, estimated using different methods including urinary sodium excretion. The outcomes will be systolic and diastolic blood pressure, elevated blood pressure and hypertension. If appropriate, meta analyses will be performed by pooling data across all studies together and separately for experimental and observational studies. Subgroup meta-analyses by age and body weight will be also conducted. Moreover, separate meta-analyses for different sodium intake levels will be conducted to investigate the dose-response relationship. ETHICS AND DISSEMINATION: This systematic review and meta-analysis will be published in a peer-reviewed journal. A report will be prepared for national authorities and other stakeholders in the domains of nutrition, public health, and child health in Switzerland. TRIAL REGISTRATION NUMBER: CRD42016038245. PMID- 27655264 TI - Can a mobile app improve the quality of patient care provided by trainee doctors? Analysis of trainees' case reports. AB - OBJECTIVES: To explore how a medical textbook app ('iDoc') supports newly qualified doctors in providing high-quality patient care. DESIGN: The iDoc project, funded by the Wales Deanery, provides new doctors with an app which gives access to key medical textbooks. Participants' submitted case reports describing self-reported accounts of specific instances of app use. The size of the data set enabled analysis of a subsample of 'complex' case reports. Of the 568 case reports submitted by Foundation Year 1s (F1s)/Year 2s (F2s), 142 (25%) detailed instances of diagnostic decision-making and were identified as 'complex'. We analysed these data against the Quality Improvement (QI) Framework using thematic content analysis. SETTING: Clinical settings across Wales, UK. PARTICIPANTS: Newly qualified doctors (2012-2014; n=114), F1 and F2. INTERVENTIONS: The iDoc app, powered by Dr Companion software, provided newly qualified doctors in Wales with a selection of key medical textbooks via individuals' personal smartphone. RESULTS: Doctors' use of the iDoc app supported 5 of the 6 QI elements: efficiency, timeliness, effectiveness, safety and patient centredness. None of the case reports were coded to the equity element. Efficiency was the element which attracted the highest number of case report references. We propose that the QI Framework should be expanding to include 'learning' as a 7th element. CONCLUSIONS: Access to key medical textbooks via an app provides trusted and valuable support to newly qualified doctors during a period of transition. On the basis of these doctors' self-reported accounts, our evidence indicates that the use of the app enhances efficiency, effectiveness and timeliness of patient-care in addition consolidating a safe, patient-centred approach. We propose that there is scope to extend the QI Framework by incorporating 'learning' as a 7th element in recognition of the relationship between providing high-quality care through educational engagement. PMID- 27655263 TI - Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol. AB - INTRODUCTION: Emerging evidence suggests that patient-reported outcome (PRO) specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported. HYPOTHESIS: Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points. METHODS AND ANALYSIS: Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion. ETHICS AND DISSEMINATION: The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r). TRIAL REGISTRATION NUMBER: PROSPERO CRD42016036533. PMID- 27655265 TI - Reliable Quantification of the Potential for Equations Based on Spot Urine Samples to Estimate Population Salt Intake: Protocol for a Systematic Review and Meta-Analysis. AB - BACKGROUND: Methods based on spot urine samples (a single sample at one time point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. OBJECTIVE: The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. METHODS: A systematic review and meta analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. RESULTS: The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. CONCLUSIONS: Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake. PMID- 27655266 TI - Vitamin D and allergic airway disease shape the murine lung microbiome in a sex specific manner. AB - BACKGROUND: Vitamin D is under scrutiny as a potential regulator of the development of respiratory diseases characterised by chronic lung inflammation, including asthma and chronic obstructive pulmonary disease. It has anti inflammatory effects; however, knowledge around the relationship between dietary vitamin D, inflammation and the microbiome in the lungs is limited. In our previous studies, we observed more inflammatory cells in the bronchoalveolar lavage fluid and increased bacterial load in the lungs of vitamin D-deficient male mice with allergic airway disease, suggesting that vitamin D might modulate the lung microbiome. In the current study, we examined in more depth the effects of vitamin D deficiency initiated early in life, and subsequent supplementation with dietary vitamin D on the composition of the lung microbiome and the extent of respiratory inflammation. METHODS: BALB/c dams were fed a vitamin D supplemented or -deficient diet throughout gestation and lactation, with offspring continued on this diet post-natally. Some initially deficient offspring were fed a supplemented diet from 8 weeks of age. The lungs of naive adult male and female offspring were compared prior to the induction of allergic airway disease. In further experiments, offspring were sensitised and boosted with the experimental allergen, ovalbumin (OVA), and T helper type 2-skewing adjuvant, aluminium hydroxide, followed by a single respiratory challenge with OVA. RESULTS: In mice fed a vitamin D-containing diet throughout life, a sex difference in the lung microbial community was observed, with increased levels of an Acinetobacter operational taxonomic unit (OTU) in female lungs compared to male lungs. This effect was not observed in vitamin D-deficient mice or initially deficient mice supplemented with vitamin D from early adulthood. In addition, serum 25-hydroxyvitamin D levels inversely correlated with total bacterial OTUs, and Pseudomonas OTUs in the lungs. Increased levels of the antimicrobial murine beta-defensin-2 were detected in the bronchoalveolar lavage fluid of male and female mice fed a vitamin D-containing diet. The induction of OVA-induced allergic airway disease itself had a profound affect on the OTUs identified in the lung microbiome, which was accompanied by substantially more respiratory inflammation than that induced by vitamin D deficiency alone. CONCLUSION: These data support the notion that maintaining sufficient vitamin D is necessary for optimal lung health, and that vitamin D may modulate the lung microbiome in a sex specific fashion. Furthermore, our data suggest that the magnitude of the pro inflammatory and microbiome-modifying effects of vitamin D deficiency were substantially less than that of allergic airway disease, and that there is an important interplay between respiratory inflammation and the lung microbiome. PMID- 27655267 TI - Improved survival among ICU-hospitalized patients with community-acquired pneumonia by unidentified organisms: a multicenter case-control study. AB - A retrospective analysis from prospectively collected data was conducted in intensive care units (ICUs) at 33 hospitals in Europe comparing the trend in ICU survival among adults with severe community-acquired pneumonia (CAP) due to unknown organisms from 2000 to 2015. The secondary objective was to establish whether changes in antibiotic policies were associated with different outcomes. ICU mortality decreased (p = 0.02) from 26.9 % in the first study period (2000 2002) to 15.7 % in the second period (2008-2015). Demographic data and clinical severity at admission were comparable between groups, except for age over 65 years and incidence of cardiomyopathy. Over time, patients received higher rates of combination therapy (94.3 vs. 77.2 %; p < 0.01) and early (<3 h) antibiotic delivery (72.9 vs. 50.3 %; p < 0.01); likewise, the 2008-2015 group was more likely to receive adequate antibiotic prescription [as defined by the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines] than the 2000-2002 group (70.7 vs. 48.2 %; p < 0.01). Multivariate analysis showed an independent association between decreased ICU mortality and early (<3 h) antibiotic administration [odds ratio (OR) 3.48 [1.70-7.15], p < 0.01] or adequate antibiotic prescription according to guidelines (OR 2.22 [1.11-4.43], p = 0.02). In conclusion, our findings suggest that ICU mortality in severe CAP due to unidentified organisms has decreased in the last 15 years. Several changes in management and better compliance with guidelines over time were associated with increased survival. PMID- 27655269 TI - Erratum: Transition of Patients with Esophageal Atresia to Adult Care: Results of a Transition-Specific Education Program. PMID- 27655268 TI - Spatial Distribution of Reef Fish Species along the Southeast US Atlantic Coast Inferred from Underwater Video Survey Data. AB - Marine fish abundance and distribution often varies across spatial scales for a variety of reasons, and this variability has significant ecological and management consequences. We quantified the distribution of reef-associated fish species along the southeast United States Atlantic coast using underwater video survey samples (N = 4,855 in 2011-2014) to elucidate variability within species across space, depths, and habitats, as well as describe broad-scale patterns in species richness. Thirty-two species were seen at least 10 times on video, and the most commonly observed species were red porgy (Pagrus pagrus; 41.4% of videos), gray triggerfish (Balistes capriscus; 31.0%), black sea bass (Centropristis striata; 29.1%), vermilion snapper (Rhomboplites aurorubens; 27.7%), and red snapper (Lutjanus campechanus; 22.6%). Using generalized additive models, we found that most species were non-randomly distributed across space, depths, and habitats. Most rare species were observed along the continental shelf break, except for goliath grouper (Epinephelus itajara), which was found on the continental shelf in Florida and Georgia. We also observed higher numbers of species in shelf-break habitats from southern North Carolina to Georgia, and fewer in shallower water and at the northern and southern ends of the southeast United States Atlantic coast. Our study provides the first broad-scale description of the spatial distribution of reef fish in the region to be based on fishery-independent data, reinforces the utility of underwater video to survey reef fish, and can help improve the management of reef fish in the SEUS, for example, by improving indices of abundance. PMID- 27655270 TI - In-vacuum thermolysis of ethane 1,2-diamineborane for the synthesis of ternary borocarbonitrides. AB - High-temperature (1000 degrees C) thermolytic decomposition of ethane 1,2 diamineborane (BH3NH2CH2CH2NH2BH3) deposited onto a Cu foil has been performed in an ultra-high-vacuum environment. A combined thermolytic, structural (x-ray diffraction), microscopic (scanning electron microscopy) and spectroscopic (Raman, x-ray photoemission spectroscopy) analysis, has identified a ternary borocarbonitride (BCN) compound as a result of the process. The obtained BCN compound is nanocrystalline, surrounded by crystallites of ammonium hydroxide borate hydrate. The ternary compound presents a 0.2:0.6:0.2 B:C:N composition in the bulk and 0.11:0.76:0.13 stoichiometry at the very surface, richer in C-C networks with respect to the bulk. Furthermore, the resulting BCN compound does not show oxidation at the surface due to the in-vacuum thermolysis of the single precursor. PMID- 27655271 TI - Generation of the Human Biped Stance by a Neural Controller Able to Compensate Neurological Time Delay. AB - The development of a physiologically plausible computational model of a neural controller that can realize a human-like biped stance is important for a large number of potential applications, such as assisting device development and designing robotic control systems. In this paper, we develop a computational model of a neural controller that can maintain a musculoskeletal model in a standing position, while incorporating a 120-ms neurological time delay. Unlike previous studies that have used an inverted pendulum model, a musculoskeletal model with seven joints and 70 muscular-tendon actuators is adopted to represent the human anatomy. Our proposed neural controller is composed of both feed forward and feedback controls. The feed-forward control corresponds to the constant activation input necessary for the musculoskeletal model to maintain a standing posture. This compensates for gravity and regulates stiffness. The developed neural controller model can replicate two salient features of the human biped stance: (1) physiologically plausible muscle activations for quiet standing; and (2) selection of a low active stiffness for low energy consumption. PMID- 27655272 TI - Impact of peer-led quality improvement networks on quality of inpatient mental health care: study protocol for a cluster randomized controlled trial. AB - BACKGROUND: Quality improvement networks are peer-led programmes in which members of the network assess the quality of care colleagues provide according to agreed standards of practice. These networks aim to help members identify areas of service provision that could be improved and share good practice. Despite the widespread use of peer-led quality improvement networks, there is very little information about their impact. We are conducting a cluster randomized controlled trial of a quality improvement network for low-secure mental health wards to examine the impact of membership on the process and outcomes of care over a 12 month period. METHODS: Standalone low secure units in England and Wales that expressed an interest in joining the quality improvement network were recruited for the study from 2012 to 2014. Thirty-eight units were randomly allocated to either the active intervention (participation in the network n = 18) or a control arm (delayed participation in the network n = 20). Using a 5 % significance level and 90 % power, it was calculated that a sample size of 60 wards was required taking into account a 10 % drop out. A total of 75 wards were assessed at baseline and 8 wards dropped out the study before the data collection at follow up. Researchers masked to the allocation status of the units assessed all study outcomes at baseline and follow-up 12 months later. The primary outcome is the quality of the physical environment and facilities on the wards. The secondary outcomes are: safety of the ward, patient-rated satisfaction with care and mental well-being, staff burnout, training and supervision. Relative to control wards, it is hypothesized that the quality of the physical environment and facilities will be higher on wards in the active arm of the trial 12 months after randomization. DISCUSSION: To our knowledge, this is the first randomized evaluation of a peer-led quality improvement network that has examined the impact of participation on both patient-level and service-level outcomes. The study has the potential to help shape future efforts to improve the quality of inpatient care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79614916 . Retrospectively registered 28 March 2014]. PMID- 27655274 TI - Procalcitonin Impairs Endothelial Cell Function and Viability. AB - BACKGROUND: Procalcitonin is used as a diagnostic tool for the identification and risk stratification of septic patients. Procalcitonin plasma concentrations tightly correlate with the severity of the ongoing inflammatory reaction and can rise up to 10,000-fold. Impairment of endothelial cell function plays an important role in the pathogenesis of hypotension and disturbed organ perfusion during sepsis. We investigated the possible effects of procalcitonin itself on endothelial cell function and viability. METHODS: Human endothelial cells were exposed to 0.01 to 100 ng/mL procalcitonin and investigated for endothelial permeability using transwells, migration in a scratch wound assay and new capillary formation on extracellular matrix in vitro. Tumor necrosis factor-alpha and vascular endothelial growth factor served as positive controls. Procalcitonin's impact on the response of endothelial cells toward ischemia was investigated in vivo in the murine model of unilateral femoral artery ligation. Procalcitonin-exposed endothelial cells were subjected to immunoblot for the investigation of vascular endothelial-cadherin expression and angiogenic signaling pathways. Flow cytometry was used for the detection of inflammatory activation and viability, and genomic analysis was performed. Data are presented as difference in means and 95% confidence intervals; statistical analyses were performed using analysis of variance/Bonferroni, and P values are reported as adjusted for multiple comparisons (Padjust). RESULTS: Tumor necrosis factor-alpha and 0.1 ng/mL procalcitonin induced endothelial barrier disruption after incubation of endothelial monolayers for 6 hours (-2.53 [-4.16 to -0.89], P = .0008 and -2.09 [-3.73 to -0.45], Padjust = .0064 compared with vehicle-treated control, respectively). Procalcitonin beginning at concentrations of 0.02 ng/mL reduced endothelial cell migration (0.26 [0.06 to 0.47], Padjust = .0069) and new capillary formation in vitro (0.47 [0.28 to 0.66], Padjust < .0001) contrasting the proangiogenic action of vascular endothelial growth factor. Left ventricular injection of procalcitonin in mice on postoperative day 1, 3, and 5 after induction of ischemia impaired new capillary formation and recovery of hindlimb perfusion in vivo (number of capillaries/mm in the ischemic leg of vehicle treated versus procalcitonin-treated mice, 852.6 [383.4-1322], Padjust = .0002). Twenty-four-hour incubation with procalcitonin reduced the expression of vascular endothelial-cadherin at 100 ng/mL (0.39 [0.06-0.71], Padjust = .0167) and induced endothelial cell death (apoptosis, -5.4 [-10.67 to -0.13], Padjust = .0431). No alteration in the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 or extracellular signal-regulated kinase 1/2, and AKT signaling pathways was observed. Genomic analysis revealed regulation of a variety of genes involved in inflammation, angiogenesis, and cell growth. CONCLUSIONS: This study found that procalcitonin itself impaired several aspects of endothelial cell function. Procalcitonin-induced loss of endothelial barrier function may contribute to capillary leakage and therapy-refractory hypotension during sepsis. Anti-angiogenic properties of procalcitonin at low concentrations could also identify procalcitonin as a mediator of vascular disease associated with the metabolic syndrome. Future studies are needed to further test procalcitonin as a potential therapeutic target for preserving vascular dysfunction during acute and chronic inflammatory disorders. PMID- 27655273 TI - Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans. AB - Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions. PMID- 27655275 TI - The Importance of Developing Standardized Transparent Validation of Large Data. PMID- 27655276 TI - Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: A Randomized, Controlled Trial of Buccal RAE Tube Oxygen Administration. AB - BACKGROUND: Despite optimal preoxygenation, obese patients undergoing induction of general anesthesia exhibit significant hypoxemia after 2 to 4 minutes of apnea. Apneic oxygenation techniques can assist airway management by extending the safe apnea time. We hypothesized that a novel method of apneic oxygenation via the oral route would effectively prolong safe apnea in an obese surgical population. METHODS: In this open-label, parallel-arm, randomized-controlled efficacy trial, 40 ASA physical status I-II obese patients with body mass index (BMI) 30-40 were randomly assigned to standard care (n = 20) or buccal oxygenation (n = 20) during induction of total IV anesthesia. Buccal oxygen was administered via a modified 3.5-mm Ring-Adair-Elwyn (RAE) tube apposed to the left internal cheek. Prolonged laryngoscopy maintained apnea with a patent airway until SpO2 dropped below 95% or 750 seconds elapsed. The primary outcome was time to reach SpO2 < 95%. RESULTS: Patient characteristics were similar in both study arms. Recipients of buccal oxygenation were less likely to exhibit SpO2 < 95% during 750 seconds of apnea; hazard ratio 0.159 (95% confidence interval 0.044 0.226, P < .0001). Median (interquartile range [IQR]) apnea times with SpO2 >= 95% were prolonged in this group; 750 (389-750) versus 296 (244-314) seconds, P < .0001. CONCLUSIONS: Clinically important prolongation of safe apnea times can be achieved delivering buccal oxygen to obese patients on induction of anesthesia. This novel use of apneic oxygenation via the oral route may improve management of the difficult airway and overcome some of the limitations of alternative techniques. PMID- 27655278 TI - Indigenous Continuous Positive Airway Pressure Device for Mitigation of Hypoxemia During One Lung Ventilation. PMID- 27655279 TI - A Survey of Intravenous Remifentanil Use for Labor Analgesia at Academic Medical Centers in the United States. AB - Remifentanil is most commonly offered when neuraxial labor analgesia is contraindicated. There is no consensus regarding the optimal administration, dosing strategy, or requirements for maternal monitoring, which may pose a patient safety issue. This exploratory survey evaluated the current practices regarding remifentanil use for labor analgesia at academic centers in the United States. Of 126 obstetric anesthesia directors surveyed, 84 (67%) responded. In 2014 to 2015, an estimated 36% (95% confidence interval: 25.7-46.3) of centers used remifentanil, most of which did so less than 5 times. Some serious maternal and neonatal respiratory complications occurred, emphasizing that clinical protocols and adequate monitoring are key to ensure maternal and neonatal safety. PMID- 27655280 TI - Important Outcomes Should Be Reported. PMID- 27655282 TI - A new argasid tick species (Acari: Argasidae) associated with the rock cavy, Kerodon rupestris Wied-Neuwied (Rodentia: Caviidae), in a semiarid region of Brazil. AB - BACKGROUND: The rock cavy Kerodon rupestris (Wied-Neuwied, 1820) is a rodent species endemic to northeastern Brazil. Earlier studies have associated the argasid tick Ornithodoros talaje (Guerin-Meneville, 1849) with rocky cavy; however, a recent study proposed that O. talaje is not established in Brazil, where previous reports of this species were possibly misidentifications of closely related species, yet to be properly determined. Here, we describe a new species of Ornithodoros Koch, 1844 associated with rock cavies in northeastern Brazil. METHODS: During 2012-2013, Ornithodoros ticks were collected from K. rupestris resting places in Paraiba State (PB) and Piaui State (PI), northeastern Brazil. These ticks were brought alive to the laboratory, and used to form two laboratory colonies (PB and PI ticks). Field-collected adults and laboratory reared larvae were used for morphological description through light and scanning electron microscopy. DNA sequences of the mitochondrial 16S rRNA gene were generated from nymphal ticks and used to conduct phylogenetic analyses along with other Ornithodoros spp. sequences from GenBank. Reproductive compatibility of crosses between PB and PI adult ticks was evaluated, as well as analyses of hybrid ticks through larval morphology by a principal components analysis (PCA) and DNA sequences of the second internal transcribed spacer (ITS2) region from adult ticks. RESULTS: Morphological analysis allowed recognizing these ticks as a new species, Ornithodoros rietcorreai n. sp. The larva of O. rietcorreai is distinct from those of other Ornithodoros spp. by the combination of the following character states: 14 pairs of dorsal setae, dorsal plate pyriform, hypostome with pointed apex and dental formula 3/3 anteriorly, 2/2 posteriorly, and anal valves with long and pointed leaf-shaped ends. There were a few larval morphological differences between PB and PI ticks, and their mitochondrial 16S rDNA sequences diverged by 3.3 %. On the other hand, cross-mating experiments showed that PB and PI ticks were reproductive compatible, indicating that they represent a single species. Analyses of ITS2 sequences and PCA corroborated this assumption. CONCLUSION: Ornithodoros rietcorreai is described as a new species associated with K. rupestris in Brazil, increasing the Brazilian tick fauna to 70 species. PMID- 27655283 TI - Untargeted LC-HRMS-Based Metabolomics for Searching New Biomarkers of Pancreatic Ductal Adenocarcinoma: A Pilot Study. AB - Pancreatic ductal adenocarcinoma is one of the most lethal tumors since it is usually detected at an advanced stage in which surgery and/or current chemotherapy have limited efficacy. The lack of sensitive and specific markers for diagnosis leads to a dismal prognosis. The purpose of this study is to identify metabolites in serum of pancreatic ductal adenocarcinoma patients that could be used as diagnostic biomarkers of this pathology. We used liquid chromatography-high-resolution mass spectrometry for a nontargeted metabolomics approach with serum samples from 28 individuals, including 16 patients with pancreatic ductal adenocarcinoma and 12 healthy controls. Multivariate statistical analysis, which included principal component analysis and partial least squares, revealed clear separation between the patient and control groups analyzed by liquid chromatography-high-resolution mass spectrometry using a nontargeted metabolomics approach. The metabolic analysis showed significantly lower levels of phospholipids in the serum from patients with pancreatic ductal adenocarcinoma compared with serum from controls. Our results suggest that the liquid chromatography-high-resolution mass spectrometry-based metabolomics approach provides a potent and promising tool for the diagnosis of pancreatic ductal adenocarcinoma patients using the specific metabolites identified as novel biomarkers that could be used for an earlier detection and treatment of these patients. PMID- 27655284 TI - The role of stem cells in benign tumors. AB - As stem cells contribute to the development and homeostasis of normal adult tissues, malfunction of stem cells in self-renewal and differentiation has been associated with tumorigenesis. A growing number of evidences indicating that tumor initiating cells play a crucial role, not only in malignancies, but also in generation and development of benign tumors. Here we offer an overview of the identification and functional characterization of benign tumor initiating cells in several tissues and organs, which typically show capacities of uncontrolled self-renewal to fuel the tumor growth and abnormal differentiation to give rise to tumor heterogeneity. They may originate from alteration of normal stem cells, which confer the benign tumor initiating cells with different repertoire of "stemness". The plastic functions of benign tumor initiating cells are determined by niche regulation mediated via several signaling and epigenetic cues. Therefore, targeting stem cell function represents an important strategy for understanding the biology and management of benign tumors. PMID- 27655285 TI - Expression and prognostic value of E2F activators in NSCLC and subtypes: a research based on bioinformatics analysis. AB - E2F activators (E2F1-3) codify a family of transcription factors (TFs) in higher eukaryotes. E2F activators are involved in the cell cycle regulation and synthesis of DNA in mammalian cells, and their overexpression has been detected in many human cancers. However, their clinical significance has not been deeply researched in non-small-cell lung cancer (NSCLC), and bioinformatics analysis has never been reported to explore their clinical role in NSCLC. In the current study, we investigated the expression and prognostic value of E2F activators in NSCLC patients through the "TCGA datasets" and the "Kaplan-Meier plotter" (KM plotter) database. Hazard ratio (HR), 95 % confidence intervals, and log-rank P were calculated. Compared with normal tissue samples, E2F activators were overexpressed in NSCLC tissues, in lung adenocarcinoma (LUAD) tissues, and in lung squamous cell carcinoma (LUSC) tissues. In NSCLC patients, E2F1 expression was significantly correlated with age, sex, and tumor stage. E2F2 expression was found to be significantly correlated with sex and tumor size. We further demonstrated that E2F1 and E2F2 overexpressions were significantly associated with poor prognosis. In LUAD patients, E2F1 expression was significantly correlated with tumor size and tumor stage. E2F2 expression was significantly correlated with lymph node status and tumor stage. E2F1 and E2F2 overexpression showed a significant association with poor prognosis, while E2F3 overexpression was significantly correlated to better prognosis. In LUSC patients, E2F1 was concluded to be significantly correlated with tumor stage. However, E2F activators were not found to be correlated to prognosis. PMID- 27655286 TI - MiR-203 promotes the growth and migration of ovarian cancer cells by enhancing glycolytic pathway. AB - MicroRNAs (miRNAs) play an important role in the tumorigenesis of ovarian cancer. Previously, we have reported the dysregulation of miR-203 in the ovarian cancer tissues. However, the biological functions and molecular mechanisms of miR-203 in ovarian cancer remain unknown. Here, we showed that the expression of miR-203 was increased in ovarian cancer tissues compared with the adjacent non-cancerous tissues and the transcription of miR-203 was inhibited by P53. Forced expression of miR-203 in ovarian cancer promoted cell growth and migration, while depletion of miR-203 inhibited the growth and migration of ovarian cancer cells. In addition, miR-203 promoted the metastasis of ovarian cancer cells in vivo and shorted the survival of the nude mice. Mechanically, miR-203 targeted the 3'-UTR of pyruvate dehydrogenase B (PDHB) and increased the consumption of glucose and the production of lactate. Overexpression of PDHB abolished the oncogenic effects of miR-203 on the growth of ovarian cancer cells. Together, our data suggested the oncogenic roles of miR-203 in ovarian cancer by promoting glycolysis, and miR 203 might be a therapeutic target for ovarian cancer. PMID- 27655287 TI - Gamma-synuclein binds to AKT and promotes cancer cell survival and proliferation. AB - Hyperactivation of AKT plays a critical role in the survival and proliferation of cancer cells. However, the molecular mechanisms underlying AKT activation remain elusive. Here, we tested the effect of gamma-synuclein, a member of the synuclein family of proteins, on the activation of AKT. We show that the expression level of gamma-synuclein is increased in non-small cell lung cancer (NSCLC) tissues. gamma-Synuclein binds to the protein kinase domain of AKT and promotes its phosphorylation. Overexpression of gamma-synuclein in H157 cells enhances cell proliferation and protects the cells from staurosporine-induced cytotoxicity. Knockdown of gamma-synuclein attenuates AKT activation and cell proliferation induced by epidermal growth factor. The effect of gamma-synuclein is abolished when AKT is depleted. Thus, gamma-synuclein promotes cell survival and proliferation via activating AKT and may play a causal role in the pathogenesis of NSCLC. PMID- 27655289 TI - Delirium is not associated with anticholinergic burden or polypharmacy in older patients on admission to an acute hospital: an observational case control study. AB - BACKGROUND: Older people are commonly prescribed multiple medications, including medications with anticholinergic effects. Polypharmacy and anticholinergic medications may be risk factors for the development of delirium. METHODS: Patients from a medical admission unit who were over 70, with DSM-IV diagnosed delirium and patients without delirium, were investigated. Number of drugs prescribed on admission and anticholinergic burden using two scales (the Anticholinergic Cognitive Burden Scale [ACB] and the Anticholinergic Drug Scale [ADS]) were recorded from electronic prescribing records. The relationship and predictive ability of these were explored. RESULTS: The sample included 125 patients with DSM-IV diagnosed delirium and 122 patients without delirium. The mean age of the sample was 84.0 years. The median number of drugs prescribed was 7: 79.8 % were prescribed >=5 drugs and 29.0 % >=10 drugs. The median ACB score was 1 and the median ADS score was 1.5. 73.4 % of patients had an ACB score of >=1 and 73.0 % had a ADS score >=1. There was no association between: number of drugs prescribed, rate of polypharmacy, rate of excessive polypharmacy, ACB score and ADS score, and a diagnosis of delirium on admission. Only acetylcholinesterase inhibitor use predicted delirium (OR 3.86, p = 0.04) and the number of drugs prescribed was negatively correlated with age (spearman rho = 0.18, p = 0.006). CONCLUSION: Neither number of drugs prescribed, polypharmacy or anticholinergic burden were associated with delirium on admission, questioning the clinical usefulness of anticholinergic drug scales. Further research is needed to unpick fully the relationship between, drugs, anticholinergic burden, age, and prevalent delirium in older patients and whether there is any role for these scales in clinical practice. PMID- 27655290 TI - Pituitary abscess with unusual MRI appearance. PMID- 27655288 TI - Low expression of MAP1LC3B, associated with low Beclin-1, predicts lymph node metastasis and poor prognosis of gastric cancer. AB - Since the roles of autophagy in gastric cancer remain unclear, we aim to investigate the expression of autophagy-related proteins MAP1LC3B and Beclin-1 in human gastric cancer and discuss their clinical significance and correlation with prognosis of patients with gastric cancer. A total of 160 consecutive patients with gastric cancer who had undergone gastrectomy were enrolled in this study. The expressions of MAP1LC3B and Beclin-1 were assessed by immunohistochemistry. The protein expression rates were analyzed with chi 2 and Fisher's exact tests. Survival analysis (overall survival (OS) and relapse-free survival (RFS)) was determined using the Kaplan-Meier method and Cox's proportional hazard regression model. Both the expressions of MAP1LC3B and Beclin-1 were lower in gastric cancer tissues than adjacent normal tissues (57 vs. 82 %, p = 0.007; 72 vs. 88 %, p = 0.046, respectively). Relativity analysis indicated MAP1LC3B expression was positively correlated with Beclin-1 expression (r = 0.424, p < 0.001). Both the MAP1LC3B-high-expression patients and Beclin-1-high-expression patients have longer OS time and RFS time than MAP1LC3B-low-expression patients and Beclin-1 low-expression patients (MAP1LC3B: both p < 0.001; Beclin-1: p = 0.014, p = 0.015, respectively). High simultaneous MAP1LC3B and Beclin-1 expressions were associated with longer OS and RFS compared with low simultaneous MAP1LC3B and Beclin-1 expressions (56.77 vs. 24.42 months, p < 0.001; 53.56 vs. 22.33 months, p < 0.001, respectively). Multivariate survival analysis showed both MAP1LC3B and Beclin-1 were independent prognostic factors for OS time (p = 0.016, p = 0.041, respectively). However, MAP1LC3B (p = 0.022) was an independent prognostic factor for RFS. Moreover, low expressions of MAP1LC3B and Beclin-1 were significantly associated with lymph node metastasis (p = 0.007, p = 0.030, respectively). The loss of MAP1LC3B, correlated with loss of Beclin-1, was observed in gastric cancer and correlated with poor prognosis and lymph node metastasis of gastric cancer patients. PMID- 27655291 TI - Thyroglobulin levels measured at the time of remnant ablation to predict response to treatment in differentiated thyroid cancer after thyroid hormone withdrawal or recombinant human TSH. AB - The objective of our study was to evaluate the prognostic value of stimulated thyroglobulin levels at the moment of remnant ablation for predicting an initial excellent or a structural incomplete response to treatment according to the risk of recurrence in patients with differentiated thyroid cancer. Patients were divided into two groups according to the preparation mode for remnant ablation (thyroid hormone withdrawal or recombinant human TSH). We included 219 patients followed-up for at least for 24 months after remnant ablation. The primary endpoint was the best response to initial therapy assessed in the first 9-18 months of follow-up. An excellent response was observed in 45.1 % of patients prepared after recombinant human TSH compared to 44.6 % of patients prepared after thyroid hormone withdrawal (P = NS). The cutoff value of thyroglobulin level after recombinant human TSH for predicting an excellent response was 8 ng/ml (n = 51), with a sensitivity of 73.9 %, and a positive predictive value of 61 %. It was similar for patients with low vs. intermediate to high risk of recurrence. This cutoff value for thyroglobulin level after thyroid hormone withdrawal was 22 ng/ml (n = 168), with a sensitivity of 94.7 % and a positive predictive value of 61.7 %. In the thyroid hormone withdrawal group the thyroglobulin cutoff level was 12 ng/ml for low-risk patients compared to 16 ng/ml for those with intermediate to high risk of recurrence (P = 0.003). The cutoff value of the thyroglobulin level for predicting a structural incomplete response to initial treatment was 20 ng/ml after rhTSH, with a negative predictive value of 91.4 %. This level was higher in thyroid hormone withdrawal group, and it was established at 25 ng/ml, with a negative predictive value of 97.7 %. The stimulated Tg level seems to be different depending on the preparation mode (rhTSH or THW) for RA. It has a high NPV to predict the absence of a structural incomplete response and it is also a good predictor of the initial excellent response and the NED status at the end of follow-up . PMID- 27655292 TI - Spontaneous intermittent MRI changes of a pituitary stalk lesion causing diabetes insipidus and amenorrhea. AB - Lymphocytic infundibulo-neurohypophysitis is a rare disorder. We report the case of a 29 year-old woman with diabetes insipidus and amenorrhea, in whom the magnetic resonance imaging demonstration of a pituitary stalk lesion was intermittent. We suggest that, in patients with endocrine dysfunction and positivity of circulating antipituitary antibodies at high title, magnetic resonance imaging should be repeated after few months, if negative. PMID- 27655293 TI - Molecular characterization of extended-spectrum beta-lactamase, plasmid-mediated AmpC cephalosporinase and carbapenemase genes among Enterobacteriaceae isolates in five medical centres of East and West Azerbaijan, Iran. AB - Very little is known about the occurrence and various types of extended-spectrum beta-lactamase (ESBL), AmpC and carbapenemase in Iran. The aims of this study were to determine the prevalence of ESBLs, AmpCs and carbapenemase genes among Enterobacteriaceae in Azerbaijan and to characterize the genetic composition of the detected genes. A total of 307 Enterobacteriaceae isolates, recovered from five medical centres, were screened for ESBL, AmpC and carbapenemase activities by the disc diffusion method and phenotypic confirmatory tests. The 162 selected strains (third-generation cephalosporins, cefoxitin- or carbapenem-resistant strains with positive or negative phenotypic confirmatory tests) were selected for multiplex PCR screening for beta-lactamase genes, and detected genes were confirmed by sequencing. Of 162 isolates, 156 harboured 1 to 6 beta-lactamase genes of 41 types. The most prevalent genes were blaTEM-1 (29.9 %), followed by blaCTX-M-15 (25.7 %). Plasmid-mediated AmpC was detected in 66 strains (21.5 %) alone or in combination with other genes. Carbapenemase-encoding genes were detected in 18 strains (5.8 %) of 27 carbapenem-non-susceptible isolates including 11, 7, 3 and 1 cases of blaOXA-48, blaNDM-1, blaKPC-2 and blaKPC-3 genes, respectively. Interestingly, 148 (94.8 %) of 156 strains with any beta lactamase gene were found to have a multidrug-resistant pattern. The rate of resistance to beta-lactams and multidrug-resistant Enterobacteriaceae is high in Azerbaijan. All positive strains for carbapenemase genes were resistant to all beta-lactams. The present study reveals the high occurrence of CTX-M-type ESBLs followed by TEM and SHV variants among Enterobacteriaceae isolates. East Azerbaijan seems to be an alarming focus for OXA-48, NDM-1 and KPC dissemination. PMID- 27655294 TI - Binary information propagation in circular magnetic nanodot arrays using strain induced magnetic anisotropy. AB - Nanomagnetic logic has emerged as a potential replacement for traditional Complementary Metal Oxide Semiconductor (CMOS) based logic because of superior energy-efficiency (Salahuddin and Datta 2007 Appl. Phys. Lett. 90 093503, Cowburn and Welland 2000 Science 287 1466-68). One implementation of nanomagnetic logic employs shape-anisotropic (e.g. elliptical) ferromagnets (with two stable magnetization orientations) as binary switches that rely on dipole-dipole interaction to communicate binary information (Cowburn and Welland 2000 Science 287 1466-8, Csaba et al 2002 IEEE Trans. Nanotechnol. 1 209-13, Carlton et al 2008 Nano Lett. 8 4173-8, Atulasimha and Bandyopadhyay 2010 Appl. Phys. Lett. 97 173105, Roy et al 2011 Appl. Phys. Lett. 99 063108, Fashami et al 2011 Nanotechnology 22 155201, Tiercelin et al 2011 Appl. Phys. Lett. 99 , Alam et al 2010 IEEE Trans. Nanotechnol. 9 348-51 and Bhowmik et al 2013 Nat. Nanotechnol. 9 59-63). Normally, circular nanomagnets are incompatible with this approach since they lack distinct stable in-plane magnetization orientations to encode bits. However, circular magnetoelastic nanomagnets can be made bi-stable with a voltage induced anisotropic strain, which provides two significant advantages for nanomagnetic logic applications. First, the shape-anisotropy energy barrier is eliminated which reduces the amount of energy required to reorient the magnetization. Second, the in-plane size can be reduced (~20 nm) which was previously not possible due to thermal stability issues. In circular magnetoelastic nanomagnets, a voltage induced strain stabilizes the magnetization even at this size overcoming the thermal stability issue. In this paper, we analytically demonstrate the feasibility of a binary 'logic wire' implemented with an array of circular nanomagnets that are clocked with voltage-induced strain applied by an underlying piezoelectric substrate. This leads to an energy efficient logic paradigm orders of magnitude superior to existing CMOS-based logic that is scalable to dimensions substantially smaller than those for existing nanomagnetic logic approaches. The analytical approach is validated with experimental measurements conducted on dipole coupled Nickel (Ni) nanodots fabricated on a PMN-PT (Lead Magnesium Niobate-Lead Titanate) sample. PMID- 27655296 TI - Analysis of the frequency of EGFR, KRAS and ALK mutations in patients with lung adenocarcinoma in Croatia. AB - BACKGROUND: Many studies have been published on the mutational status of patients with lung adenocarcinomas, and great population-based variability in mutation frequencies has been reported. The main objective of the present study was to analyze the EGFR, KRAS and ALK mutation status in a representative cohort of patients in Croatia with lung adenocarcinomas and to correlate the mutational status with clinical data. METHODS: All patients who were newly diagnosed within 6 months with histologically proven primary lung adenocarcinomas were included. Mutational analyses for EGFR and KRAS mutations were performed in a cobas z 480 analyzer. ALK immunohistochemistry was performed using the D5F3 clone on Benchmark XT instrument. Clinical data were obtained from the medical records. RESULTS: Of the 324 patients, 59.9 % were male. At the time of diagnosis, the patients ranged in age range from 35 to 88 years (median 63 years). Most of the patients were current smokers or former smokers (77.2 %). EGFR mutations were found in 15.7 % of the patients, and of these mutations, exon 19 deletion was the most common (45.1 %). KRAS mutations were present in 34.9 % of the patients, while 4.1 % of patients were ALK-positive. The statistical significance of the presence of mutations was detected for both gender and smoking. CONCLUSION: The detected mutation rates demonstrated a slightly higher prevalence of KRAS mutations, but not a higher prevalence of EGFR mutations or ALK gene rearrangement, in comparison with the rates found in other European countries. EGFR and ALK mutational status showed a statistically significant correlation with gender as well as with smoking, while KRAS mutation status showed a statistically significant correlation only with smoking. PMID- 27655295 TI - Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication. AB - Acute organophosphorus (OP) intoxication is a worldwide clinical and public health problem. In addition to cholinergic crisis, neurodegeneration and brain damage are hallmarks of the severe form of this toxidrome. Recently, we generated a chemical model of severe acute OP intoxication in zebrafish that is characterized by altered head morphology and brain degeneration. The pathophysiological pathways resulting in brain toxicity in this model are similar to those described in humans. The aim of this study was to assess the predictive power of this zebrafish model by testing the effect of a panel of drugs that provide protection in mammalian models. The selected drugs included "standard therapy" drugs (atropine and pralidoxime), reversible acetylcholinesterase inhibitors (huperzine A, galantamine, physostigmine and pyridostigmine), N-methyl D-aspartate (NMDA) receptor antagonists (MK-801 and memantine), dual-function NMDA receptor and acetylcholine receptor antagonists (caramiphen and benactyzine) and anti-inflammatory drugs (dexamethasone and ibuprofen). The effects of these drugs on zebrafish survival and the prevalence of abnormal head morphology in the larvae exposed to 4 uM chlorpyrifos oxon [1 * median lethal concentration (LC50)] were determined. Moreover, the neuroprotective effects of pralidoxime, memantine, caramiphen and dexamethasone at the gross morphological level were confirmed by histopathological and transcriptional analyses. Our results demonstrated that the zebrafish model for severe acute OP intoxication has a high predictive value and can be used to identify new compounds that provide neuroprotection against severe acute OP intoxication. PMID- 27655298 TI - Intraoperative optical coherence tomography in descemet stripping automated endothelial keratoplasty: pilot experiences. AB - PURPOSE: To assess the added value of intraoperative optical coherence tomography (iOCT) in evaluating graft adhesion and graft interface in patients undergoing descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: This is a prospective single-center case series comprising 8 eyes of 8 patients consecutively scheduled for DSAEK surgery. iOCT imaging was performed after insertion of the graft, after pressurizing the eye, and at the end of surgery (three images per surgery). At each stage of surgery, corneal thickness and the widest gap between the recipient and the graft (i.e., maximal interface width) were measured using an image processing tool. Follow-up measurements were taken at 1 day, 3 and 6 months, post-operatively. RESULTS: Imaging was performed in 21 of 24 scheduled imaging intervals, and required little to no additional surgical time. At the end of surgery, iOCT showed persisting interfaces in six cases. One case showed a full graft detachment necessitating surgical intervention. CONCLUSION: Real-time iOCT is a safe, efficient, and useful tool in assessing graft adherence in DSAEK surgery. With adequate analysis software, iOCT has the potential to be a paradigm-shifting development in posterior lamellar surgery and could aid the clinician in further lowering the rates of graft dislocation after DSAEK. PMID- 27655299 TI - Genotyping analysis of the factor V Nara mutation, Hong Kong mutation, and 16 single-nucleotide polymorphisms, including the R2 haplotype, and the involvement of factor V activity in patients with recurrent miscarriage. AB - : Recurrent miscarriage can arise from a large diversity of causes and the factors responsible have not been fully clarified. The coagulation factor V R506Q (Leiden) mutation is a well known risk factor for recurrent miscarriage, although it has not been found in Japanese populations. We examined whether the factor V Nara and Hong Kong mutations, the factor V gene (F5) 16 single-nucleotide polymorphisms (SNPs), including the factor V R2 haplotype, and plasma factor V activity (FV:C) were risk factors for recurrent miscarriage. A cross-sectional study was conducted among 88 patients with a history of unexplained recurrent miscarriage and 95 fertile controls. None of the patients or controls was homozygous or heterozygous for the factor V Nara or Hong Kong mutation. In the 16 SNPs of F5, frequencies of the G/T and T/T genotypes at Ser156Ser were significantly lower in patients than in controls (OR 0.45, 95% CI 0.22-0.91, OR 0.32, 95% CI 0.14-0.72) and the allele frequency of C at Leu1288Leu was significantly higher in patients than that in controls (OR 1.66, 95% CI 1.02 2.71). The mean FV:C values were not significantly different between patients and controls. However, the prevalence of patients with a high or low FV:C (>95th or 12 months before the Cito-test) were tested. RESULTS: In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 +/- 9.5). Scores were different across gender and levels of household income (p < 0.05). Scores of early starters were significantly higher than starters within 12 months (533.7 +/- 1.7 vs. 524.1 +/- 2.6). CONCLUSION: This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research. PMID- 27655330 TI - Incretin-Based Therapy and Risk of Pancreatic Cancer in Patients with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials. AB - INTRODUCTION: The present study aims to evaluate the risk of pancreatic cancer with incretin-based therapy among patients with type 2 diabetes mellitus (T2DM). METHODS: We searched EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for eligible studies published up to March 06 2016. This meta-analysis includes all studies reporting adverse events of pancreatic cancer with use of incretin-based therapies compared with placebo or non-incretin anti-diabetic drugs in patients with T2DM. We used fixed-effect model to compare pooled relative risk (RR) with related 95% confidence intervals (CI). RESULTS: A total of 159 randomized trials were identified. Out of these, 135 studies were excluded as pancreatic cancer occurrence had not been included as an end point. The remaining 24 trials enrolling 47,904 participants were further assessed. Overall, no increased risk of pancreatic cancer were detected in association with incretin-based treatment (RR = 0.7, 95% CI 0.37-1.05). The incidence of pancreatic neoplasm was even lower among incretin-based groups than controls (RR = 0.50, 95% CI 0.29-0.87) in trials with duration more than 104 weeks. There was even decreased risk of pancreatic cancer within groups paralleled by incretin matched placebos (RR = 0.55, 95% CI 0.32-0.93) than by non-incretin anti-diabetic drugs. Neither monotherapy (RR = 0.62, 95% CI 0.38-1.01) nor combination regimen (RR = 0.92, 95% CI 0.45-1.90) of incretin mimetics increased the risk of pancreatic cancer. CONCLUSION: This meta-analysis shows that incretin-based therapies are not associated with increase in the risk of pancreatic cancer. Interestingly, subgroup analyses suggested lower risk of pancreatic cancer in incretin groups than placebo in long-term studies (>104 weeks). Considering the inconsistent results among randomized trials and previous epidemiological investigations, more such studies should be conducted to clarify the existence or non-existence of this association. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81270476 and 81470830). PMID- 27655331 TI - Inter-class competition in stage-structured populations: effects of adult density on life-history traits of adult and juvenile common lizards. AB - Ecological and evolutionary processes in natural populations are largely influenced by the population's stage-structure. Commonly, different classes have different competitive abilities, e.g., due to differences in body size, suggesting that inter-class competition may be important and largely asymmetric. However, experimental evidence states that inter-class competition, which is important, is rare and restricted to marine fish. Here, we manipulated the adult density in six semi-natural populations of the European common lizard, Zootoca vivipara, while holding juvenile density constant. Adult density affected juveniles, but not adults, in line with inter-class competition. High adult density led to lower juvenile survival and growth before hibernation. In contrast, juvenile survival after hibernation was higher in populations with high adult density, pointing to relaxed inter-class competition. As a result, annual survival was not affected by adult density, showing that differences in pre- and post-hibernation survival balanced each other out. The intensity of inter-class competition affected reproduction, performance, and body size in juveniles. Path analyses unravelled direct treatment effects on early growth (pre-hibernation) and no direct treatment effects on the parameters measured after hibernation. This points to allometry of treatment-induced differences in early growth, and it suggests that inter-class competition mainly affects the early growth of the competitively inferior class and thereby their future performance and reproduction. These results are in contrast with previous findings and, together with results in marine fish, suggest that the strength and direction of density dependence may depend on the degree of inter-class competition, and thus on the availability of resources used by the competing classes. PMID- 27655332 TI - Statewide Study to Assess Nurses' Experiences With Meaningful Use-Based Electronic Health Records. AB - Nursing professionals are at the frontline of the health information technology revolution. The Texas Nurses Association and Texas Organization of Nurse Executives partnered to evaluate the changing health technology environment in Texas, in particular the nurses' satisfaction with the use of clinical information systems. A descriptive exploratory study using the Clinical Information System Implementation Evaluation Scale and a newly developed Demographic Survey and the Meaningful Use Maturity-Sensitive Index, with a narrative component, was conducted in 2014 and 2015. Nurses across Texas received an electronic invitation to participate in the survey, resulting in 1177 respondents. Exploratory factor analysis revealed that variables of the Meaningful Use Maturity-Sensitive Index and Clinical Information System Implementation Evaluation Scale show strong interrater reliability, with Cronbach's alpha scores of .889 and .881, respectively, and thereby inform the survey analysis, indicating and explaining variations in regional and institutional trends with respect to satisfaction. For example, the maturity of a clinical information system within an organization and age of the nurse significantly influence the probability of nurse satisfaction (P < .05). Qualitative analysis of nurses' narratives further explained the nurses' experiences. Recommendations for future research and educational were identified. PMID- 27655333 TI - Identification potential biomarkers in pulmonary tuberculosis and latent infection based on bioinformatics analysis. AB - BACKGROUND: The study aimed to identify the potential biomarkers in pulmonary tuberculosis (TB) and TB latent infection based on bioinformatics analysis. METHODS: The microarray data of GSE57736 were downloaded from Gene Expression Omnibus database. A total of 7 pulmonary TB and 8 latent infection samples were used to identify the differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was constructed by Cytoscape software. Then network based neighborhood scoring analysis was performed to identify the important genes. Furthermore, the functional enrichment analysis, correlation analysis and logistic regression analysis for the identified important genes were performed. RESULTS: A total of 1084 DEGs were identified, including 565 down- and 519 up regulated genes. The PPI network was constructed with 446 nodes and 768 edges. Down-regulated genes RIC8 guanine nucleotide exchange factor A (RIC8A), basic leucine zipper transcription factor, ATF-like (BATF) and microtubule associated monooxygenase, calponin LIM domain containing 1 (MICAL1) and up-regulated genes ATPase, Na+/K+ transporting, alpha 4 polypeptide (ATP1A4), histone cluster 1, H3c (HIST1H3C), histone cluster 2, H3d (HIST2H3D), histone cluster 1, H3e (HIST1H3E) and tyrosine kinase 2 (TYK2) were selected as important genes in network-based neighborhood scoring analysis. The functional enrichment analysis results showed that these important DEGs were mainly enriched in regulation of osteoblast differentiation and nucleoside triphosphate biosynthetic process. The gene pairs RIC8A-ATP1A4, HIST1H3C-HIST2H3D, HIST1H3E-BATF and MICAL1-TYK2 were identified with high positive correlations. Besides, these genes were selected as significant feature genes in logistic regression analysis. CONCLUSIONS: The genes such as RIC8A, ATP1A4, HIST1H3C, HIST2H3D, HIST1H3E, BATF, MICAL1 and TYK2 may be potential biomarkers in pulmonary TB or TB latent infection. PMID- 27655334 TI - "Inherently chiral" thiophene-based electrodes at work: a screening of enantioselection ability toward a series of pharmaceutically relevant phenolic or catecholic amino acids, amino esters, and amine. AB - "Inherently chiral" thiophene-based electroactive oligomer films have recently been shown to exhibit outstanding chirality manifestations. One of the most exciting among them is an unprecedented enantioselection ability as electrode surfaces. In fact, in preliminary chiral voltammetry experiments, the new electrodes have been shown to both discriminate the enantiomers of chiral probes (either enantiopure or in a mixture, in terms of large differences in peak potentials) and quantify them (in terms of linear dynamic ranges in peak currents), without the need for preliminary separation steps. Such ability has now been tested on a series of chiral DOPA-related molecules, from phenolic amino acid tyrosine (together with its methyl ester) to catecholic amino acid DOPA (together with its methyl ester), to catecholamine epinephrine (adrenaline). The wide-range enantioselectivity of the new inherently chiral electrode surfaces is fully confirmed, as large peak potential differences are obtained for probe enantiomers of the whole series working in common aqueous buffers. Moreover, interesting modulating effects on enantiodiscrimination can be observed as a function of both molecular structure and pH. Graphical abstract Inherently chiral thiophene-based electrodes at work with pharmaceutically relevant probes. PMID- 27655335 TI - A fluorescent probe assay (Heparin Red) for direct detection of heparins in human plasma. AB - Heparins are widely used anticoagulant drugs. The current monitoring practice for heparin in plasma, such as the chromogenic anti-factor Xa assay, relies on heparin-triggered activation of antithrombin, an inhibitor of coagulation proteases. Such assays are not applicable to the detection of non-anticoagulant heparins, an emerging class of drug candidates for therapeutic applications unrelated to anticlotting activity. This study describes the application of a commercially available fluorescent probe assay (Heparin Red) for the direct and sensitive detection of the "chemical" heparin in plasma, independent of any anticoagulant activity. The quantification range is about 0-5 MUg/mL for both unfractionated heparin (corresponding to 0-1 IU/mL) and the low molecular weight heparin enoxaparin. The Heparin Red assay is of particular value for the quantification of non-anticoagulant heparins, as exemplified by the low molecular weight heparin derivative tafoxiparin and a N-desulfated-N-reacetylated heparin. Heparin octa- and decasaccharides are also detected. Graphical abstract Heparin quantification in plasma by mixing the sample with the Heparin Red reagent and fluorescence readout. PMID- 27655336 TI - Micro-liquid chromatography mass spectrometry for the analysis of antineoplastic drugs from wipe samples. AB - A fast quantification method for the determination of 11 antineoplastic drugs from wipe samples was developed using micro-scale liquid chromatography in combination with tandem mass spectrometry. The extraction efficiency from the wipes has been investigated using different extraction solvents. The results indicate that a mixture of 70/30 water/isopropanol (v/v) acidified with 0.1 % formic acid is suitable to desorb the antineoplastic drugs with sufficient recovery between 80 and 120 %. Compared to conventional liquid chromatography, the total analysis time can be reduced to 2.25 min using a 50 * 0.3 mm column at a flow rate of 25 MUL min-1. Ion source parameters as well as the injection volume were optimized to ensure the highest sensitivity. The results of method validation showed an instrumental limit of quantification between 0.0068 and 0.0488 ng mL-1 using an injection volume of 4.25 MUL estimated by the signal to noise ratio. Moreover, the retention time repeatability was determined with a maximum relative standard deviation of 0.4 %. Graphical abstract Micro-LC-MS/MS separation of 11 antineoplastic drugs from wipe samples. PMID- 27655338 TI - Specific Bacillus subtilis 168 variants form biofilms on nutrient-rich medium. AB - Bacillus subtilis is an intensively studied Gram-positive bacterium that has become one of the models for biofilm development. B. subtilis 168 is a well-known domesticated strain that has been suggested to be deficient in robust biofilm formation. Moreover, the diversity of available B. subtilis laboratory strains and their derivatives have made it difficult to compare independent studies related to biofilm formation. Here, we analysed numerous 168 stocks from multiple laboratories for their ability to develop biofilms in different set-ups and media. We report a wide variation among the biofilm-forming capabilities of diverse stocks of B. subtilis 168, both in architecturally complex colonies and liquid-air interface pellicles, as well as during plant root colonization. Some 168 variants are indeed unable to develop robust biofilm structures, while others do so as efficiently as the non-domesticated NCIB 3610 strain. In all cases studied, the addition of glucose to the medium dramatically improved biofilm development of the laboratory strains. Furthermore, the expression of biofilm matrix component operons, epsA-O and tapA-sipW-tasA, was monitored during colony biofilm formation. We found a lack of direct correlation between the expression of these genes and the complexity of wrinkles in colony biofilms. However, the presence of a single mutation in the exopolysaccharide-related gene epsC correlates with the ability of the stocks tested to form architecturally complex colonies and pellicles, and to colonize plant roots. PMID- 27655339 TI - Involved field radiotherapy (IFRT) versus elective nodal irradiation (ENI) for locally advanced non-small cell lung cancer: a meta-analysis of incidence of elective nodal failure (ENF). AB - BACKGROUND AND PURPOSE: The use of involved field radiotherapy (IFRT) has generated concern about the increasing incidence of elective nodal failure (ENF) in contrast to elective nodal irradiation (ENI). This meta-analysis aimed to provide more reliable and up-to-date evidence on the incidence of ENF between IFRT and ENI. MATERIALS AND METHODS: We searched three databases for eligible studies where locally advanced non-small cell lung cancer (NSCLC) patients received IFRT or ENI. Outcome of interest was the incidence of ENF. The fixed effects model was used to pool outcomes across the studies. RESULTS: There were 3 RCTs and 3 cohort studies included with low risk of bias. There was no significant difference in incidence of ENF between IFRT and ENI either among RCTs (RR = 1.38, 95 % CI: 0.59-3.25, p = 0.46) or among cohort studies (RR = 0.99, 95 % CI: 0.46-2.10, p = 0.97). There was also no significant difference in incidence of ENF between IFRT and ENI when RCTs and cohort studies were combined (RR = 1.15, 95 % CI: 0.65-2.01, p = 0.64). I 2 of test for heterogeneity was 0 %. CONCLUSION: This meta-analysis provides more reliable and stable evidence that there is no significant difference in incidence of ENF between IFRT and ENI. PMID- 27655340 TI - Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model. AB - BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology and suggest new targets for treatment. METHODS: We investigate the disease phenotype of TSC by neural differentiation of a human stem cell model that had been deleted for TSC2 by genome editing. Comprehensive genomic analysis was performed by RNA sequencing and ribosome profiling to obtain a detailed genome-wide description of alterations on both the transcriptional and translational level. The molecular effect of mTOR inhibitors used in the clinic was monitored and comparison to published data from patient biopsies and mouse models highlights key pathogenic processes. RESULTS: TSC2 deficient neural stem cells showed severely reduced neuronal maturation and characteristics of astrogliosis instead. Transcriptome analysis indicated an active inflammatory response and increased metabolic activity, whereas at the level of translation ribosomal transcripts showed a 5'UTR motif-mediated increase in ribosome occupancy. Further, we observed enhanced protein synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but transcriptional dysfunction persisted. CONCLUSIONS: Our results extend the understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. PMID- 27655337 TI - Obesity and stroke: Can we translate from rodents to patients? AB - Obesity is a risk factor for stroke and is consequently one of the most common co morbidities found in patients. There is therefore an identified need to model co morbidities preclinically to allow better translation from bench to bedside. In preclinical studies, both diet-induced and genetically obese rodents have worse stroke outcome, characterised by increased ischaemic damage and an altered inflammatory response. However, clinical studies have reported an 'obesity paradox' in stroke, characterised by reduced mortality and morbidity in obese patients. We discuss the potential reasons why the preclinical and clinical studies may not agree, and review the mechanisms identified in preclinical studies through which obesity may affects stroke outcome. We suggest inflammation plays a central role in this relationship, as obesity features increases in inflammatory mediators such as C-reactive protein and interleukin-6, and chronic inflammation has been linked to worse stroke risk and outcome. PMID- 27655343 TI - Rapid mapping of compound eye visual sampling parameters with FACETS, a highly automated wide-field goniometer. AB - A highly automated goniometer instrument (called FACETS) has been developed to facilitate rapid mapping of compound eye parameters for investigating regional visual field specializations. The instrument demonstrates the feasibility of analyzing the complete field of view of an insect eye in a fraction of the time required if using non-motorized, non-computerized methods. Faster eye mapping makes it practical for the first time to employ sample sizes appropriate for testing hypotheses about the visual significance of interspecific differences in regional specializations. Example maps of facet sizes are presented from four dipteran insects representing the Asilidae, Calliphoridae, and Stratiomyidae. These maps provide the first quantitative documentation of the frontal enlarged facet zones (EFZs) that typify asilid eyes, which, together with the EFZs in male Calliphoridae, are likely to be correlated with high-spatial-resolution acute zones. The presence of EFZs contrasts sharply with the almost homogeneous distribution of facet sizes in the stratiomyid. Moreover, the shapes of EFZs differ among species, suggesting functional specializations that may reflect differences in visual ecology. Surveys of this nature can help identify species that should be targeted for additional studies, which will elucidate fundamental principles and constraints that govern visual field specializations and their evolution. PMID- 27655341 TI - Automating NEURON Simulation Deployment in Cloud Resources. AB - Simulations in neuroscience are performed on local servers or High Performance Computing (HPC) facilities. Recently, cloud computing has emerged as a potential computational platform for neuroscience simulation. In this paper we compare and contrast HPC and cloud resources for scientific computation, then report how we deployed NEURON, a widely used simulator of neuronal activity, in three clouds: Chameleon Cloud, a hybrid private academic cloud for cloud technology research based on the OpenStack software; Rackspace, a public commercial cloud, also based on OpenStack; and Amazon Elastic Cloud Computing, based on Amazon's proprietary software. We describe the manual procedures and how to automate cloud operations. We describe extending our simulation automation software called NeuroManager (Stockton and Santamaria, Frontiers in Neuroinformatics, 2015), so that the user is capable of recruiting private cloud, public cloud, HPC, and local servers simultaneously with a simple common interface. We conclude by performing several studies in which we examine speedup, efficiency, total session time, and cost for sets of simulations of a published NEURON model. PMID- 27655342 TI - Executive Functioning and Engagement in Physical and Relational Aggression among Children with ADHD. AB - Although evidence suggests that executive functioning (EF) impairments are implicated in physically aggressive behavior (e.g., hitting) these cognitive impairments have rarely been examined with regard to relational aggression (e.g., gossip, systematic exclusion). Studies also have not examined if EF impairments underlie the expression of aggression in children with attention deficit/hyperactivity disorder (ADHD) and if child gender moderates risk. Children with and without clinical elevations in ADHD symptoms (N = 124; ages 8 12 years; 48 % male) completed a battery of EF tests. Parent and teacher report of ADHD and oppositional defiant disorder (ODD) symptoms and teacher report of engagement in physical and relational aggression were collected. Models tested the unique association of EF abilities with physical and relational aggression and the indirect effect through the expression of ADHD or ODD behaviors; child gender was also tested as a moderator. EF impairment was uniquely associated with physical aggression, but better EF ability was associated with relational aggression. For boys, poor EF also was indirectly associated with greater physical aggression through the expression of ADHD behaviors. However, ADHD symptoms were unrelated to relational aggression. ODD symptoms also predicted physical aggression for boys but relational aggression for girls. Results suggest that there are multiple and distinct factors associated with engagement in physical and relational aggression and that better EF may actually promote relational aggression. Established models of physical aggression should not be assumed to map on to explanations of relational aggression. PMID- 27655346 TI - A Basal Tapejarine (Pterosauria; Pterodactyloidea; Tapejaridae) from the Crato Formation, Early Cretaceous of Brazil. AB - A three-dimensional and almost complete pterosaur mandible from the Crato Formation (Early Cretaceous of Northeastern Brazil), Araripe Basin, is described as a new species of a tapejarine tapejarid. Tapejarines are a particular group of toothless pterosaurs, characterized by well-developed cranial crests, downturned rostra, and have been proposed to represent frugivorous flying reptiles. Though comparatively well represented and distributed, the evolutionary history of the group is still poorly known, and the internal relationships of its members are not well understood. The new species here reported, named Aymberedactylus cearensis gen. et sp. nov., adds new data concerning the evolution of the group, concerning their morphology and geographical origin. It differs from known tapejarids due to its unusually elongate retroarticular process and a shallow fossa on the splenial exhibiting distinctive rugose texture. Furthermore, it exhibits a suite of basal and derived conditions within the Tapejaridae, demonstrating how their morphological traits probably evolved and that these forms were even more diverse than already acknowledged. The discovery of Aymberedactylus cearensis sheds new light on the evolutionary history of the Tapejarinae. PMID- 27655344 TI - Heavy Alcohol Consumption with Alcoholic Liver Disease Accelerates Sarcopenia in Elderly Korean Males: The Korean National Health and Nutrition Examination Survey 2008-2010. AB - BACKGROUND AND AIM: Although a few studies have reported that sarcopenia is associated with alcoholic liver disease (ALD), no studies have investigated this association in a large sample representative of the elderly Korean population. METHODS: This was a cross-sectional study that used data from the Fourth and Fifth Korean National Health and Nutrition Examination Surveys (KNHANES) on subjects aged 65 years and older. Sarcopenia was defined as a skeletal muscle index (SMI) more than 1 SD below the gender-specific mean for young adults; SMI was calculated as the appendicular muscle mass divided by height squared (ASM/Ht2). Heavy alcohol consumption was defined as consuming at least 210 g/week, and elevated liver enzymes were defined as alanine aminotransferase levels of at least 32 U/L or aspartate aminotransferase levels of at least 34 U/L. ALD was defined as heavy alcohol consumption and elevated liver enzymes. RESULTS: The mean age of the 1,151 elderly males was 71.6 +/- 0.2 years, and the prevalence of heavy alcohol consumption was 11.8% (136 subjects). SMI did not differ between the non-heavy and heavy alcohol consumer groups (7.1 +/- 0.0 kg/m2 vs. 7.3 +/- 0.1 kg/m2, respectively, P = 0.145). However, after stratifying by the presence of liver disease and heavy alcohol consumption and adjusting for other confounders in the multivariate logistic regression, SMI was significantly lower among heavy alcohol consumers with ALD (all P < 0.05). Additionally, two way ANOVA showed a significant interaction between heavy alcohol consumption and liver disease (P = 0.011). CONCLUSION: Sarcopenia was accelerated in the elderly male ALD group, with a significant interaction between alcohol consumption and liver disease. PMID- 27655345 TI - Stage-dependent fate of Plasmodium falciparum-infected red blood cells in the spleen and sickle-cell trait-related protection against malaria. AB - BACKGROUND: Sickle-cell trait (HbAS) reduces falciparum malaria risk and suppresses parasitaemia. Although several candidate mechanisms have been proposed, their epidemiological, clinical and experimental correlates have not been adequately explained. To explore the basis for generally lower parasitaemias and delayed malaria episodes in children with HbAS, it is hypothesized here that their spleen-dependent removal of ring-infected red blood cells (RBCs) is more efficient than in children with normal haemoglobin A (HbAA). METHODS: The mechanical splenic retention of Plasmodium falciparum-infected RBCs from subjects with HbAS or HbAA was investigated using two physiologically relevant methods: microsphiltration and ex vivo spleen perfusion. P. falciparum-infected RBCs obtained from in vitro cultures and from patients were used in either normoxic or hypoxic conditions. The effect of sickling in ring-infected HbAS RBCs was also investigated. RESULTS: When a laboratory-adapted parasite strain was analysed, ring-infected HbAA RBCs were retained in microsphilters at similar or greater levels than ring-infected HbAS RBCs, under normoxic (retention rate 62.5 vs 43.8 %, P < 0.01) and hypoxic (54.0 vs 38.0 %, P = 0.11) conditions. When parasitized RBCs from Malian children were analysed, retention of ring-infected HbAA and HbAS RBCs was similar when tested either directly ex vivo (32.1 vs 28.7 %, P = 0.52) or after one re-invasion in vitro (55.9 vs 43.7 %, P = 0.30). In hypoxia, sickling of uninfected and ring-infected HbAS RBCs (8.6 vs 5.7 %, P = 0.51), and retention of ring-infected HbAA and HbAS RBCs in microsphilters (72.5 vs 68.8 %, P = 0.38) and spleens (41.2 vs 30.4 %, P = 0.11), also did not differ. Retention of HbAS and HbAA RBCs infected with mature P. falciparum stages was greater than 95 %. CONCLUSIONS: Sickle-cell trait is not associated with higher retention or sickling of ring-infected RBCs in experimental systems reflecting the mechanical sensing of RBCs by the human spleen. As observed with HbAA RBCs, HbAS RBCs infected with mature parasites are completely retained. Because the cytoadherence of HbAS RBCs infected with mature parasites is impaired, the very efficient splenic retention of such non-adherent infected RBCs is expected to result in a slower rise of P. falciparum parasitaemia in sickle-cell trait carriers. PMID- 27655347 TI - Watch Out for Your Neighbor: Climbing onto Shrubs Is Related to Risk of Cannibalism in the Scorpion Buthus cf. occitanus. AB - The distribution and behavior of foraging animals usually imply a balance between resource availability and predation risk. In some predators such as scorpions, cannibalism constitutes an important mortality factor determining their ecology and behavior. Climbing on vegetation by scorpions has been related both to prey availability and to predation (cannibalism) risk. We tested different hypotheses proposed to explain climbing on vegetation by scorpions. We analyzed shrub climbing in Buthus cf. occitanus with regard to the following: a) better suitability of prey size for scorpions foraging on shrubs than on the ground, b) selection of shrub species with higher prey load, c) seasonal variations in prey availability on shrubs, and d) whether or not cannibalism risk on the ground increases the frequency of shrub climbing. Prey availability on shrubs was compared by estimating prey abundance in sticky traps placed in shrubs. A prey sample from shrubs was measured to compare prey size. Scorpions were sampled in six plots (50 m x 10 m) to estimate the proportion of individuals climbing on shrubs. Size difference and distance between individuals and their closest scorpion neighbor were measured to assess cannibalism risk. The results showed that mean prey size was two-fold larger on the ground. Selection of particular shrub species was not related to prey availability. Seasonal variations in the number of scorpions on shrubs were related to the number of active scorpions, but not with fluctuations in prey availability. Size differences between a scorpion and its nearest neighbor were positively related with a higher probability for a scorpion to climb onto a shrub when at a disadvantage, but distance was not significantly related. These results do not support hypotheses explaining shrub climbing based on resource availability. By contrast, our results provide evidence that shrub climbing is related to cannibalism risk. PMID- 27655348 TI - An Extended Structure-Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors. AB - Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca2+ channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure-activity relationship and a quantitative structure-activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [3H]Ryanodine ([3H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta substitutions to the para-position resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs. PMID- 27655349 TI - Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels. AB - Microglia are considered to be the resident immune cells of the central nervous system and contribute significantly to ongoing neuroinflammation in a variety of neurodegenerative diseases. Recently, we and others identified that voltage-gated sodium channels (VGSC) are present on microglia cells and contribute to excessive accumulation of intracellular Na+ and release of major pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Based on this finding and the fact that pyrethroid pesticides act on VGSC, we hypothesized that exposure of microglia to the pyrethroid pesticides, permethrin and deltamethrin, would activate microglia and increase the release of TNF-alpha. BV2 cells or primary microglia were treated with 0-5 uM deltamethrin or permethrin in the presence or absence of tetrodotoxin (TTX), a VGSC blocker for 24-48 h. Both pyrethroids caused a rapid Na+ influx and increased accumulation of intracellular sodium [(Na+)i] in the microglia in a dose- and time-dependent manner, which was significantly reduced by TTX. Furthermore, deltamethrin and permethrin increased the release of TNF alpha in a dose- and time-dependent manner, which was significantly reduced by pre-treatment of cells with TTX. These results demonstrate that pyrethroid pesticides may directly activate microglial cells through their interaction with microglial VGSC. Because neuroinflammation plays a key role in many neurodegenerative diseases, these data provide an additional mechanism by which exposure to pyrethroid insecticides may contribute to neurodegeneration. PMID- 27655350 TI - Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors. AB - Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD). No liver injury has been observed with tolvaptan treatment in healthy subjects and in non-ADPKD indications, but ADPKD clinical trials showed evidence of drug-induced liver injury (DILI). Although all DILI events resolved, additional monitoring in tolvaptan-treated ADPKD patients is required. In vitro assays identified alterations in bile acid disposition and inhibition of mitochondrial respiration as potential mechanisms underlying tolvaptan hepatotoxicity. This report details the application of DILIsym software to determine whether these mechanisms could account for the liver safety profile of tolvaptan observed in ADPKD clinical trials. DILIsym simulations included physiologically based pharmacokinetic estimates of hepatic exposure for tolvaptan and2 metabolites, and their effects on hepatocyte bile acid transporters and mitochondrial respiration. The frequency of predicted alanine aminotransferase (ALT) elevations, following simulated 90/30 mg split daily dosing, was 7.9% compared with clinical observations of 4.4% in ADPKD trials. Toxicity was multifactorial as inhibition of bile acid transporters and mitochondrial respiration contributed to the simulated DILI. Furthermore, simulation analysis identified both pre-treatment risk factors and on-treatment biomarkers predictive of simulated DILI. The simulations demonstrated that in vivo hepatic exposure to tolvaptan and the DM-4103 metabolite, combined with these 2 mechanisms of toxicity, were sufficient to account for the initiation of tolvaptan-mediated DILI. Identification of putative risk-factors and potential novel biomarkers provided insight for the development of mechanism-based tolvaptan risk-mitigation strategies. PMID- 27655352 TI - Increased yield of beta-glucosidase-catalyzed hydrolysis reactions in the presence of betaine-type metabolite analog. AB - beta-Glucosidases (EC 3.2.1.21), abundant enzymes distributed in animals, plants and microorganism, has been generating lots of attentions for bioethanol production from cellulosic biomass. In this study, using three different origins of beta-glucosidases, glucose productivity of beta-glucosidase-catalyzed hydrolysis reactions in the presence of synthetic betaine-type metabolite analog (2-N,N,N-tri-n-butylammonium) acetate, was investigated. By the addition of the analog, the hydrolysis yields for all beta-glucosidases was highly improved from 4-13 to 64-100 %. To understand the factors affecting on the yield enhancements, the kinetic parameters, inhibition constants of end-product and temporal stability of beta-glucosidases were compared. As a result, enhancement of the yields is mainly related to the increase in the temporal stability of beta glucosidases in the presence of the analog. The present findings lead to not only improve the glucose productivity of beta-glucosidase-catalyzed hydrolysis reaction toward bioethanol production but also apply to a new stabilization method for various unstable enzymes. PMID- 27655351 TI - A comparative assessment of generalized anxiety, conduct and peer relationship problems among AIDS and other orphaned children in India. AB - BACKGROUND: Data on mental health among orphaned children in India are scanty. We compared the generalized anxiety, conduct and peer relationship problems and their associated risk factors among children orphaned by HIV/AIDS and those due to other reasons in the Indian city of Hyderabad. METHODS: Four hundred orphaned children aged 12 to 16 years residing in orphanages in Hyderabad were sampled, half being AIDS orphans (COA) and the rest orphaned due to other reasons (COO). Interviews were done using standardized scales to assess generalized anxiety, conduct and peer relationship problems. A score >8, >4, and >5 was considered as indicator of generalized anxiety, conduct problem and peer relationship problem, respectively. Variations in the intensity of these three conditions due to possible factors including co-existing depression were assessed using multiple classification analysis (MCA). RESULTS: A total of 396 (99.3 %) orphans participated of whom 199 (50.3 %) were COA. The mean generalized anxiety, conduct and peer relationship problem scores were 11.1 (SD 5.2), 3.8 (SD 2.5) and 3.8 (SD 2.5) for COA; and 7.6 (SD 4), 2.6 (SD 2) and 2.3 (SD 1.8) for COO, respectively. Among COA, the prevalence of generalized anxiety score of >8 was 74.4 % (95 % CI 67.8-80.0 %), of conduct problem score of >4 was 33.2 % (95 % CI 26.9-40.1 %), and of peer relationship problem score of >5 was 27.6 %, (95 % CI 21.8-34.3 %), with these being significantly lower in COO. In MCA, a higher mean depression score had the highest effect on the intensity of generalized anxiety, conduct and peer relationship problem (Beta 0.477; 0.379 and 0.453 respectively); being COA and a girl had the most impact on generalized anxiety (0.100 and 0.115, respectively). CONCLUSIONS: A significantly high proportion of AIDS orphans deal with generalized anxiety, conduct and peer relationship problem as compared with other orphans highlighting the need to address the poor mental health of orphans in India. PMID- 27655353 TI - How to assess intra- and inter-observer agreement with quantitative PET using variance component analysis: a proposal for standardisation. AB - BACKGROUND: Quantitative measurement procedures need to be accurate and precise to justify their clinical use. Precision reflects deviation of groups of measurement from another, often expressed as proportions of agreement, standard errors of measurement, coefficients of variation, or the Bland-Altman plot. We suggest variance component analysis (VCA) to estimate the influence of errors due to single elements of a PET scan (scanner, time point, observer, etc.) to express the composite uncertainty of repeated measurements and obtain relevant repeatability coefficients (RCs) which have a unique relation to Bland-Altman plots. Here, we present this approach for assessment of intra- and inter-observer variation with PET/CT exemplified with data from two clinical studies. METHODS: In study 1, 30 patients were scanned pre-operatively for the assessment of ovarian cancer, and their scans were assessed twice by the same observer to study intra-observer agreement. In study 2, 14 patients with glioma were scanned up to five times. Resulting 49 scans were assessed by three observers to examine inter observer agreement. Outcome variables were SUVmax in study 1 and cerebral total hemispheric glycolysis (THG) in study 2. RESULTS: In study 1, we found a RC of 2.46 equalling half the width of the Bland-Altman limits of agreement. In study 2, the RC for identical conditions (same scanner, patient, time point, and observer) was 2392; allowing for different scanners increased the RC to 2543. Inter-observer differences were negligible compared to differences owing to other factors; between observer 1 and 2: -10 (95 % CI: -352 to 332) and between observer 1 vs 3: 28 (95 % CI: -313 to 370). CONCLUSIONS: VCA is an appealing approach for weighing different sources of variation against each other, summarised as RCs. The involved linear mixed effects models require carefully considered sample sizes to account for the challenge of sufficiently accurately estimating variance components. PMID- 27655354 TI - Absolute Quantification of Rifampicin by MALDI Imaging Mass Spectrometry Using Multiple TOF/TOF Events in a Single Laser Shot. AB - Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) allows for the visualization of molecular distributions within tissue sections. While providing excellent molecular specificity and spatial information, absolute quantification by MALDI IMS remains challenging. Especially in the low molecular weight region of the spectrum, analysis is complicated by matrix interferences and ionization suppression. Though tandem mass spectrometry (MS/MS) can be used to ensure chemical specificity and improve sensitivity by eliminating chemical noise, typical MALDI MS/MS modalities only scan for a single MS/MS event per laser shot. Herein, we describe TOF/TOF instrumentation that enables multiple fragmentation events to be performed in a single laser shot, allowing the intensity of the analyte to be referenced to the intensity of the internal standard in each laser shot while maintaining the benefits of MS/MS. This approach is illustrated by the quantitative analyses of rifampicin (RIF), an antibiotic used to treat tuberculosis, in pooled human plasma using rifapentine (RPT) as an internal standard. The results show greater than 4-fold improvements in relative standard deviation as well as improved coefficients of determination (R2) and accuracy (>93% quality controls, <9% relative errors). This technology is used as an imaging modality to measure absolute RIF concentrations in liver tissue from an animal dosed in vivo. Each microspot in the quantitative image measures the local RIF concentration in the tissue section, providing absolute pixel-to-pixel quantification from different tissue microenvironments. The average concentration determined by IMS is in agreement with the concentration determined by HPLC-MS/MS, showing a percent difference of 10.6%. Graphical Abstract ?. PMID- 27655355 TI - Comparison of methods for assessing temporal variation of growth of fungi on building materials. AB - Fungal growth on indoor surfaces can decay building materials and release hazardous substances that affect indoor air quality. Despite the numerous methods available for growth determination, there is no commonly accepted standard. The goal of this study was to compare five different assay methods for the measurement of fungal growth: cultivation, MS-based determination of ergosterol, beta-N-acetylhexosaminidase activity, quantitative PCR and microscopic spore counting. Three fungal species (Aspergillus puulaauensis, Cladosporium montecillanum and Penicillium polonicum) were grown on three different building materials (two types of acoustic board and wood). Fungal load was determined at different time points. Results from all of the methods, except the spore count, showed good correlation between each other (r=0.6-0.8). Results obtained with the cultivation method had the highest variability among replicate samples (65 %), making it the least reproducible in repeated measurements. However, it also displayed the highest variability in incubation times (149 %), indicating its suitability for detecting transient changes in the physiological state of cells. Similar to the cultivation method, quantitative PCR correlated well with the other methods and had high variability in incubation times but had lower variability among replicate samples. Ergosterol and beta-N-acetylhexosaminidase enzyme activity seemed to be the methods least dependent on the physiological state of the cells. Varying growth dynamics were observed for different species over time with the different assay methods. Each one of the tests provides a different perspective on fungal quantification due to its specific responses to the various stages of fungal growth. PMID- 27655356 TI - Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors. AB - Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images. PMID- 27655359 TI - A missing link in the bench-to-bedside paradigm: engaging regulatory stakeholders in clinical genomics research. AB - For genomic medicine research to be fully translated into clinical care, it is critical for researchers to engage stakeholders who ultimately regulate the use of genomic technologies and therapeutics within healthcare practice. Herein, we describe an example of how this might work. PMID- 27655358 TI - Turning perception on its head: cephalic perception of whole and partial length of a wielded object. AB - Flexibility is a fundamental hallmark of perceptual systems. In particular, there is a great deal of flexibility in the ability to perceive properties of occluded objects by effortful or dynamic touch-hefting, wielding, or otherwise manipulating those objects by muscular effort. Perception of length of an occluded wielded object is comparable when that object is wielded by anatomical components that differ in sensitivity, dexterity, and functionality. Moreover, perception of this property is supported by an analogous sensitivity to inertial properties across such components. We investigated the ability to perceive whole and partial length of an object wielded by hand or by head. Experiment 1 found that perception of length by these anatomical components is qualitatively and quantitatively indistinguishable. Experiment 2 found that perception of length is supported by the same specific sensitivity to inertial properties in each case. Experiment 3 found that perception of whole length and partial length are each supported by specific sensitivities to inertial properties and that this is the case for both hand and by head. The results are discussed in the context of the nature of the stimulation patterns and the organization of the haptic system that are likely to support such flexibility in perception. PMID- 27655357 TI - To bridge or not to bridge the multisensory time gap: bimanual coordination to sound and touch with temporal lags. AB - Living in a complex and multisensory environment involves constant interaction between perception and action. There is evidence that multisensory integration is governed by temporal factors, such as physiological synchrony between cross-modal stimuli favouring multisensory benefit, and the existence of a range of asynchrony between the stimuli which affords their binding (the temporal window of integration). These factors were examined in this study in a bimanual sensorimotor synchronization task with cross-modal stimuli. Participants synchronized each hand to a pair of audio-tactile stimuli, in which the asynchrony between onsets of auditory and tactile stimuli was systematically manipulated. In cross-modal conditions, they were instructed to tap either to the auditory stimuli or to tactile stimuli. The results reported a temporal window of integration of 160 ms centred around 40 and 80 ms (tactile first). Moreover, the temporal interval between the auditory and tactile stimuli affected the stability of bimanual coordination and of synchronization exclusively when participants were instructed to synchronize with tactile stimuli. Overall, the results indicate that both physiological asynchrony and temporal window of integration apply to cross-modal integration in a bimanual synchronization task. In addition, it shows the effect of auditory dominance onto multisensory temporal processes. This study sheds light on the role of temporal factors in multisensory processes when perception and actions are rhythmic and coupled. PMID- 27655360 TI - Respite Care, Stress, Uplifts, and Marital Quality in Parents of Children with Down Syndrome. AB - Parents of children with disabilities are at risk for high stress and low marital quality; therefore, this study surveyed couples (n = 112) of children with Down syndrome (n = 120), assessing whether respite hours, stress, and uplifts were related to marital quality. Structural equation modeling indicated that respite hours were negatively related to wife/husband stress, which was in turn negatively related to wife/husband marital quality. Also, wife uplifts were positively related to both wife and husband marital quality. Husband uplifts were positively related to husband marital quality. Therefore, it is important that respite care is provided and accessible to parents of children with Down syndrome. PMID- 27655361 TI - n-Butyl-α-D-fructofuranoside Isolated from Ulmus davidiana Enhances Nrf2 Activity Through Activation of JNK. AB - BACKGROUND: The root bark of Ulmus davidiana Nakai (Ulmaceae), a traditional Korean medicinal plant, is used for treating inflammatory diseases. OBJECTIVE: We investigated the Nrf2-activating effect of U. davidiana and identified a novel Nrf2 activator from its constituent compounds. METHODS: Cytotoxicity was measured by MTT assay, and the Nrf2 activity was examined by luciferasereporter assay and western blot analysis. The expression of Nrf2-dependent antioxidant genes was estimated by RT-PCR. The signal pathway related to Nrf2 activation was analyzed by treating specific signaling inhibitors. Anti-inflammatory effects were determined using an NO assay and western blot analysis. RESULTS: Ulmus davidiana and its constituent compounds, including catechin-3-O-α-L-rhamnopyranoside, α-nigerose, n-butyl α-D-fructofuranoside (NBF), and procyanidin B3, enhanced the transcriptional activity of Nrf2. Of these compounds, only NBF possessed a distinctive structure and exhibited ROS-independent Nrf2 activation. In addition, NBF significantly increased the nuclear translocation of Nrf2 and the expression of Nrf2-dependent detoxifying enzymes, including HO-1 and NQO-1, in dose-dependent manner. The Nrf2 activation induced by NBF was mediated by the phosphorylation of JNK. Consequently, pretreatment with NBF inhibited the LPS induced expression of pro-inflammatory genes. CONCLUSION: To the best of our knowledge, this is the first study to report on the Nrf2-activating effect of U. davidiana and NBF. Given the importance of Nrf2 as a negative regulator in various inflammatory diseases, NBF could be considered as a novel candidate for the prevention and treatment of inflammatory diseases. PMID- 27655362 TI - Optimization of Ultrasonic-Microwave Synergistic Extraction of Ricinine from Castor Cake by Response Surface Methodology. AB - Castor cake is the residue in castor oil production in which many active components exist and the major one among them is ricinine. In this study, optimization of extraction of ricinine from castor cake using ultrasonic microwave synergistic extraction (UMSE) was investigated to obtain high yield and purity by Box-Behnken design (BBD) response surface design. The optimal conditions of extraction were: ultrasound power 342 W, extracting time 5 min, microwave power 395 W, and non-significant factor of liquid/solid ratio 1:10. The crude extraction was recrystallized from ethanol. As a result, the maximum yield of ricinine was approximately 67.52%. The purity of ricinine was 99.39% which was determined by high performance liquid chromatography (HPLC). Additionally, the structure of purified ricinine was identified by fourier transforms infrared (FTIR) and liquid chromatography-mass spectrometry (LC-MS). Scanning electron microscope (SEM) was used to characterize the prismatic crystals morphology of ricinine. Results demonstrated that the present method combined the advantages of ultrasonic extraction and microwave extraction, which is time-saving with high extraction yield. Our results offer a suitable method for large-scale isolation of ricinine. PMID- 27655363 TI - Stereospermum fimbriatum as a Potential Source of Phytochemicals: A Review of Stereospermum Genus. AB - Stereospermum fimbriatum is one of the medicinal plants that has been claimed to be used traditionally to treat several illnesses such as stomachache, earache, skin irritation and postpartum illness. The genus of this plant is known to possess medicinal properties in every part of the plant. Therapeutic potential of S. fimbriatum is anticipated based on numerous previous studies that documented variety of phytochemical contents and bioactivity of the genus. The most reported bioactivities of its genus are antimicrobial, antioxidant, anti-diabetic, anti inflammatory, anti-diarrheal and analgesic activities. S. fimbriatum is a rare species that has not been discovered yet. Thus, this review aims at highlighting the potentials of S. fimbriatum by collecting available data on the bioactivities of its genus and set the directions for future research on this plant. PMID- 27655364 TI - Classification of biliary atresia in the laparoscopic era. AB - PURPOSE: According to Kasai's classification of biliary atresia (BA), type III is diagnosed when micro bile ducts (MBD) cannot be identified macroscopically on the surface of the biliary remnant transected at the porta hepatis. However, during laparoscopic Kasai (lapKasai), magnification produced by a 30 degrees 10 mm scope at a focal length of 5 cm is *38 and *100 when zooming, enabling more MBD to be identified than with the naked eye rendering Kasai's original classification questionable in the laparoscopic era. METHODS: Intraoperative video recordings of 36 consecutive lapKasai cases (2009-2015) were reviewed to confirm MBD visibility. 85 consecutive open Kasai cases examined macroscopically served as controls. RESULTS: MBD were not visible under regular laparoscopic magnification during lapKasai in 6/36 (lapMBD-; 16.7 %) cases and visible in 30/36 (83.3 %). However, in open cases, MBD could not be identified macroscopically in 77/85 (macroMBD-; 90.6 %), a typical result reported internationally. For our lapKasai cases, jaundice clearance was lower in lapMBD cases (4/6 = 66.7 % versus 26/30 = 86.7 %), which was not statistically significant (p = 0.26). Conversely, survival with the native liver was significantly lower in lapMBD-cases (4/6 = 66.7 % versus 23/30 = 76.7 %) (p < 0.05). CONCLUSIONS: BA classification may benefit from revision to include laparoscopic findings to categorize BA more comprehensively. PMID- 27655365 TI - Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis. AB - PURPOSE: Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS). Our aim was to conduct a systematic review of the evidence of whether post-natal erythromycin exposure is associated with subsequent development of IHPS. METHODS: A systematic review of postnatal erythromycin administration and IHPS was performed. Papers were included if data were available on development (yes/no) of IHPS in infants exposed/unexposed to erythromycin. Data were meta-analysed using Review Manager 5.3. A random effects model was decided on a priori due to heterogeneity of study design; data are odds ratio (OR) with 95 % CI. RESULTS: Nine papers reported data suitable for analysis; two randomised controlled trials and seven retrospective studies. Overall, erythromycin exposure was significantly associated with development of IHPS [OR 2.45 (1.12-5.35), p = 0.02]. However, significant heterogeneity existed between the studies (I 2 = 84 %, p < 0.0001). Data on erythromycin exposure in the first 14 days of life was extracted from 4/9 studies and identified a strong association between erythromycin exposure and subsequent development IHPS [OR 12.89 (7.67-2167), p < 0.00001]. CONCLUSION: This study demonstrates a significant association between post-natal erythromycin exposure and development of IHPS, which seems stronger when exposure occurs in the first 2 weeks of life. PMID- 27655366 TI - Altered levels of AtHSCB disrupts iron translocation from roots to shoots. AB - KEY MESSAGE: Plants overexpressing AtHSCB and hscb knockdown mutants showed altered iron homeostasis. The overexpression of AtHSCB led to activation of the iron uptake system and iron accumulation in roots without concomitant transport to shoots, resulting in reduced iron content in the aerial parts of plants. By contrast, hscb knockdown mutants presented the opposite phenotype, with iron accumulation in shoots despite the reduced levels of iron uptake in roots. AtHSCB play a key role in iron metabolism, probably taking part in the control of iron translocation from roots to shoots. Many aspects of plant iron metabolism remain obscure. The most known and studied homeostatic mechanism is the control of iron uptake in the roots by shoots. Nevertheless, this mechanism likely involves various unknown sensors and unidentified signals sent from one tissue to another which need to be identified. Here, we characterized Arabidopsis thaliana plants overexpressing AtHSCB, encoding a mitochondrial cochaperone involved in [Fe-S] cluster biosynthesis, and hscb knockdown mutants, which exhibit altered shoot/root Fe partitioning. Overexpression of AtHSCB induced an increase in root iron uptake and content along with iron deficiency in shoots. Conversely, hscb knockdown mutants exhibited increased iron accumulation in shoots and reduced iron uptake in roots. Different experiments, including foliar iron application, citrate supplementation and iron deficiency treatment, indicate that the shoot directed control of iron uptake in roots functions properly in these lines, implying that [Fe-S] clusters are not involved in this regulatory mechanism. The most likely explanation is that both lines have altered Fe transport from roots to shoots. This could be consistent with a defect in a homeostatic mechanism operating at the root-to-shoot translocation level, which would be independent of the shoot control over root iron deficiency responses. In summary, the phenotypes of these plants indicate that AtHSCB plays a role in iron metabolism. PMID- 27655367 TI - Hypofractionated boost after whole breast irradiation in breast carcinoma: chronic toxicity results and cosmesis. AB - PURPOSE: To evaluate the impact of hypofractionated boost after hypofractionated whole breast irradiation in breast carcinoma. METHODS AND MATERIALS: Patients after breast conservative surgery were treated all time with hypofractionation of 2.67 Gy/day. Whole breast dose was 40.05 Gy followed in case of risk of local relapse by a boost of 16.02 Gy or 8.01 Gy. Acute and chronic toxicity results were evaluated including cosmetic software-assisted assessment and objective evaluation of fibrosis parameters (elasticity and hydration) by means of a skin tester. RESULTS: A total of 362 patients were evaluated. Acute toxicities comprised grade 1 dermatitis in 48.1 %, grade 2 in 44.5 % and grade 3 in 17 patients 4.7 %, respectively. After a median follow-up of 4.5 years, in 308 cases (86.6 %) there was no chronic skin or subcutaneous changes. In the first consecutive 50 patients, measures with skin tester showed no statistical differences in parameters for skin and subcutaneous fibrosis. Cosmetic results were considered excellent and good in 26 and 62 %, respectively. CONCLUSIONS: Boost to tumour bed with hypofractionated doses is well tolerated and acute and chronic toxicities are mild with good cosmetic results. Objective systems are encouraging methods to assess skin quality and cosmesis. PMID- 27655368 TI - Combining PARP inhibitors with radiation therapy for the treatment of glioblastoma: Is PTEN predictive of response? AB - Glioblastoma (GBM) is fatal. The standard radiotherapy and chemotherapy (temozolomide) followed by an adjuvant phase of temozolomide provide patients with, on average, a 2.5 months benefit. New treatments that can improve sensitivity to the standard treatment are urgently needed. Herein, we review the mechanisms and utility of poly (ADP-ribose) polymerase inhibitors in combination with radiation therapy as a treatment option for GBM patients and the role of phosphatase and tensin homologue mutations as a biomarker of response. PMID- 27655369 TI - Urinary Retinol-Binding Protein: Relationship to Renal Function and Cardiovascular Risk Factors in Chronic Kidney Disease. AB - The role of urinary retinol-binding protein (RBP) as a biomarker of CKD in proximal tubular diseases, glomerulopathies and in transplantation is well established. However, whether urinary RBP is also a biomarker of renal damage and CKD progression in general CKD is not known. In this study, we evaluated the association of urinary RBP with renal function and cardiovascular risk factors in the baseline data of the Progredir Study, a CKD cohort in Sao Paulo, Brazil, comprising 454 participants with stages 3 and 4 CKD. In univariate analysis, urinary RBP was inversely related to estimated glomerular filtration rate (CKD EPI eGFR) and several cardiovascular risk factors. After adjustments, however, only CKD-EPI eGFR, albuminuria, systolic blood pressure, anemia, acidosis, and left atrium diameter remained significantly related to urinary RBP. The inverse relationship of eGFR to urinary RBP (beta-0.02 +/- 95CI -0.02; -0.01, p<0.0001 for adjusted model) remained in all strata of albuminuria, even after adjustments: in normoalbuminuria (beta-0.008 +/- 95CI (-0.02; -0.001, p = 0.03), in microalbuminuria (beta-0.02 +/- 95CI (-0.03; -0.02, p<0,0001) and in macroalbuminuria (beta-0.02 +/- 95CI (-0.03; -0.01, p<0,0001). Lastly, urinary RBP was able to significantly increase the accuracy of a logistic regression model (adjusted for sex, age, SBP, diabetes and albuminuria) in diagnosing eGFR<35 ml/min/1.73m2 (AUC 0,77, 95%CI 0,72-0,81 versus AUC 0,71, 95%CI 0,65 0,75, respectively; p = 0,05). Our results suggest that urinary RBP is significantly associated to renal function in CKD in general, a finding that expands the interest in this biomarker beyond the context of proximal tubulopathies, glomerulopathies or transplantation. Urinary RBP should be further explored as a predictive marker of CKD progression. PMID- 27655371 TI - Biofeedback in the prophylactic treatment of medication overuse headache: a pilot randomized controlled trial. AB - BACKGROUND: Medication overuse headache (MOH) is a major clinical concern and a common health risk. Recent literature stressed the need to manage chronic headache by using integrated biobehavioral approaches. Few studies evaluated how biofeedback can be useful in MOH. The aim of the study is to evaluate in a randomized, controlled, single-blind trial the effects of biofeedback associated with traditional pharmacological therapy in the prophylactic treatment of MOH. METHOD: Twenty-seven subjects were randomized to frontal electromyographic (EMG) biofeedback associated with prophylactic pharmacological therapy (Bfb Group) or to pharmacological treatment alone (Control Group). The primary outcome was to evaluate the number of patients that return episodic after treatment. Secondly we evaluate the effects of frontal EMG BFB on frequency of headache and analgesic intake. Changes in coping strategies and in EMG frontalis tension were also evaluated. ANOVA was performed on all the variables of interest. RESULTS: Our results indicate that at the end of treatment the number of patients that returned episodic in the Bfb group was significantly higher than in the Control group. Patients in the Bfb group differed from the Control group in headache frequency, amount of drug intake and active coping with pain. These outcomes were confirmed also after 4 months of follow-up. No significant effects were observed in EMG recordings. CONCLUSIONS: Biofeedback added to traditional pharmacological therapy in the treatment of MOH is a promising approach for reducing headache frequency and analgesic intake. Modification of coping cognitions in the Bfb group, as an adjunct mechanism of self-regulation, needs more evaluations to understand the role of biofeedback in changing maladaptive psychophysiological responses. PMID- 27655370 TI - The Anoikis Effector Bit1 Inhibits EMT through Attenuation of TLE1-Mediated Repression of E-Cadherin in Lung Cancer Cells. AB - The mitochondrial Bcl-2 inhibitor of transcription 1 (Bit1) protein is part of an anoikis-regulating pathway that is selectively dependent on integrins. We previously demonstrated that the caspase-independent apoptotic effector Bit1 exerts tumor suppressive function in lung cancer in part by inhibiting anoikis resistance and anchorage-independent growth in vitro and tumorigenicity in vivo. Herein we show a novel function of Bit1 as an inhibitor cell migration and epithelial-mesenchymal transition (EMT) in the human lung adenocarcinoma A549 cell line. Suppression of endogenous Bit1 expression via siRNA and shRNA strategies promoted mesenchymal phenotypes, including enhanced fibroblastoid morphology and cell migratory potential with concomitant downregulation of the epithelial marker E-cadherin expression. Conversely, ectopic Bit1 expression in A549 cells promoted epithelial transition characterized by cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Specific downregulation of E-cadherin in Bit1-transfected cells was sufficient to block Bit1-mediated inhibition of cell motility while forced expression of E-cadherin alone attenuated the enhanced migration of Bit1 knockdown cells, indicating that E-cadherin is a downstream target of Bit1 in regulating cell motility. Furthermore, quantitative real-time PCR and reporter analyses revealed that Bit1 upregulates E-cadherin expression at the transcriptional level through the transcriptional regulator Amino-terminal Enhancer of Split (AES) protein. Importantly, the Bit1/AES pathway induction of E cadherin expression involves inhibition of the TLE1-mediated repression of E cadherin, by decreasing TLE1 corepressor occupancy at the E-cadherin promoter as revealed by chromatin immunoprecipitation assays. Consistent with its EMT inhibitory function, exogenous Bit1 expression significantly suppressed the formation of lung metastases of A549 cells in an in vivo experimental metastasis model. Taken together, our studies indicate Bit1 is an inhibitor of EMT and metastasis in lung cancer and hence can serve as a molecular target in curbing lung cancer aggressiveness. PMID- 27655372 TI - Economic Burden of Disease-Associated Malnutrition at the State Level. AB - BACKGROUND: Disease-associated malnutrition has been identified as a prevalent condition, particularly for the elderly, which has often been overlooked in the U.S. healthcare system. The state-level burden of community-based disease associated malnutrition is unknown and there have been limited efforts by state policy makers to identify, quantify, and address malnutrition. The objective of this study was to examine and quantify the state-level economic burden of disease associated malnutrition. METHODS: Direct medical costs of disease-associated malnutrition were calculated for 8 diseases: Stroke, Chronic Obstructive Pulmonary Disease, Coronary Heart Failure, Breast Cancer, Dementia, Musculoskeletal Disorders, Depression, and Colorectal Cancer. National disease and malnutrition prevalence rates were estimated for subgroups defined by age, race, and sex using the National Health and Nutrition Examination Survey and the National Health Interview Survey. State prevalence of disease-associated malnutrition was estimated by combining national prevalence estimates with states' demographic data from the U.S. Census. Direct medical cost for each state was estimated as the increased expenditures incurred as a result of malnutrition. PRINCIPAL FINDINGS: Direct medical costs attributable to disease-associated malnutrition vary among states from an annual cost of $36 per capita in Utah to $65 per capita in Washington, D.C. Nationally the annual cost of disease associated malnutrition is over $15.5 billion. The elderly bear a disproportionate share of this cost on both the state and national level. CONCLUSIONS: Additional action is needed to reduce the economic impact of disease associated malnutrition, particularly at the state level. Nutrition may be a cost effective way to help address high health care costs. PMID- 27655375 TI - Impact of miniport laparoscopic cholecystectomy versus standard port laparoscopic cholecystectomy on recovery of physical activity: a randomized trial. AB - INTRODUCTION: We conducted a randomized trial comparing minilaparoscopic cholecystectomy (MLC) to conventional laparoscopic cholecystectomy (CLC) to determine whether MLC accelerated recovery of physical activity after elective surgery (NCT01397565). METHODS: A total of 115 patients scheduled for elective cholecystectomy were randomized to either CLC or MLC. Both procedures used a 10 mm umbilical port, but the three upper abdominal ports were 5 mm in CLC and 3 mm in MLC. Primary outcome was self-reported physical activity 1 month after surgery as estimated by Community Health Activities Model Program for Seniors questionnaire (kcal/kg/week). Secondary outcomes were umbilical pain, abdominal pain, nausea and fatigue (VAS, 1-10), and cosmetic result at one and 3 months. Patients received identical surgical dressings for 1 week, and assessors were blinded to group allocation. RESULTS: Forty-two patients randomized to CLC group and 33 patients randomized to MLC remained in the trial and were analyzed. Both groups were similar at baseline characteristics. In the MLC group, at least one 5 mm port was used in 17 (51.5 %) mainly due to unavailability of ML equipment. Median (IQR) physical activity for the CLC and MLC groups was similar at baseline (23.4 [13.1, 44.6] vs 23.6 [14.2, 66.9] kcal/kg/week, p = 0.35) and at 1 month (20 [7.9, 52.5] vs 16.8 [11.8, 28.6] kcal/kg/week, p = 0.90). One month post-op, umbilical pain and abdominal pain were similar, but the CLC group reported higher fatigue (4 [1-5] vs 1 [0-4], p = 0.05) and worse scar appearance scores (4 [3, 4] vs 4.5 [4, 5], p = 0.009). At 3 months, the CLC group had worse scar appearance (4 [3-5] vs 5 [4-5], p = 0.02) and lower scar satisfaction scores (4 [3, 4] vs 4 [3.5-4], p = 0.04). CONCLUSION: Recovery of physical activity was similar after MLC and CLC. MLC resulted in less fatigue and better scar appearance and satisfaction. These benefits were seen despite the need to upsize one or more ports in more than half of patients related to availability of the miniature instruments. PMID- 27655374 TI - Blood pressure and proteinuria control remains a challenge in patients with type 2 diabetes mellitus and chronic kidney disease: experience from the prospective observational ALICE-PROTECT study. AB - BACKGROUND: Type 2 diabetes (T2DM) is the leading cause of chronic kidney disease (CKD) in western countries. The combination of both increases the risk of end stage renal disease (ESRD), cardiovascular events and all-cause mortality. Early control of blood pressure (BP) and proteinuria (Pu) is crucial to slow down the progression of the CKD and prevent cardiovascular events and mortality. The primary objective of the study was to assess BP and Pu control after a 2-year follow-up in T2DM patients with CKD. METHODS: Prospective, multicenter, observational study. Overall, 153 French nephrologists included 986 T2DM patients with Pu (>=0.5 g/day) and an eGFR >15 ml/min/1.73 m2. Data from 729 patients were available after a 2-year follow-up. BP and Pu control were respectively defined as less than 140/90 mmHg and 0.5 g/day. We also looked at renal and cardiovascular events. RESULTS: At baseline, 74 % of the patients were male, mean age was 70 years. The mean T2DM duration was 17 years with a mean HbA1c of 7.4 %. All were treated for hypertension and 33 % had a controlled BP; 81 % had dyslipidemia and LDLc was <1 g/L for 54 %; 44 % had retinopathy, 40 % macrovascular complications and 12 % heart failure. Mean Pu was 2 g/day and eGFR 40 +/- 20 mL/min/1.73 m2, with 13, 18, 32 and 37 % of the patients in respectively stage 2, 3a, 3b and 4 CKD. After two years, 21 % reached the Pu target and 39 % the BP target. The mean eGFR of 40 +/- 20.3 ml/min/1.73 m2 at baseline dropped to 33.9 +/- 22.6 ml/min/1.73 m2 by year two (p < 0.001). This corresponded to a mean annual eGFR reduction of 3.2 ml/min/1.73 m2. 118 patients presented a renal event (16.2 %): doubling of serum creatinine for 86 patients (11.8 %) and start of dialysis for 72 (9.9 %); 176 patients (24.1 %) developed at least one cardiovascular complication (mainly coronary events and acute heart failure) during the follow-up period, and among these, 50 had also developed renal complications. Sixty patients died, i.e., 8.2 %, 26 patients from cardiovascular causes. CONCLUSION: Our study highlights that achieving BP and Pu targets remains a major challenge in patients with T2DM and nephropathy. Renal failure emerges as a more frequent event than death. PMID- 27655373 TI - A systematic review of physical activity and sedentary behaviour research in the oil-producing countries of the Arabian Peninsula. AB - BACKGROUND: The dramatic rise in Noncommunicable Diseases (NCD) in the oil producing countries of the Arabian Peninsula is driven in part by insufficient physical activity, one of the five main contributors to health risk in the region. The aim of this paper is to review the available evidence on physical activity and sedentary behaviour for this region. Based on the findings, we prioritize an agenda for research that could inform policy initiatives with regional relevance. METHODS: We reviewed regional evidence on physical activity and sedentary behaviour to identify the needs for prevention and policy-related research. A literature search of peer-reviewed publications in the English language was conducted in May 2016 using PubMed, Web of Science and Google Scholar. 100 studies were identified and classified using the Behavioural Epidemiology Framework. RESULTS: Review findings demonstrate that research relevant to NCD prevention is underdeveloped in the region. A majority of the studies were epidemiological in approach with few being large-scale population based studies using standardised measures. Correlates demonstrated expected associations with health outcomes, low levels of physical activity (particularly among young people), high levels of sedentary behaviour (particularly among men and young people) and expected associations of known correlates (e.g. gender, age, education, time, self-motivation, social support, and access). Very few studies offered recommendations for translating research findings into practice. CONCLUSIONS: Further research on the determinants of physical activity and sedentary behaviour in the Arabian Peninsula using standard assessment tools is urgently needed. Priority research includes examining these behaviours across the four domains (household, work, transport and leisure). Intervention research focusing on the sectors of education, health and sports sectors is recommended. Furthermore, adapting and testing international examples to the local context would help identify culturally relevant policy and programmatic interventions for the region. PMID- 27655376 TI - Technical feasibility and safety of laparoscopic right hepatectomy for hepatocellular carcinoma following sequential TACE-PVE: a comparative study. AB - BACKGROUND: Major liver resection for hepatocellular carcinoma (HCC) ideally involves preoperative portal venous embolization (PVE) coupled with preoperative transarterial chemoembolization (TACE) to improve postoperative course and oncological results. Laparoscopic right hepatectomy (RH) following sequential TACE-PVE for HCC, although challenging, may help improve both immediate and long term patient outcomes. This study is the first to describe and compare laparoscopic to open RH following sequential TACE-PVE for HCC in terms of feasibility, safety, and patient outcomes. STUDY DESIGN: All patients who underwent laparoscopic RH following successful TACE-PVE sequence (video provided) were retrospectively reviewed from a prospective database maintained at our center. Preoperative characteristics, operative data, and postoperative outcomes were analyzed and compared with those of patients who underwent open RH after TACE-PVE sequence during the same period. RESULTS: The laparoscopic and open RH groups each included 16 patients. F3 or F4 fibrosis was present in 81 % of patients. The conversion rate was 25 %. The 90-day postoperative complication rate was 25 % in the laparoscopic group versus 50 % in the open group (p = 0.27). The incidence of postoperative liver failure grade B was higher in the open group than in the laparoscopic group (5 vs. 0 patients, p = 0.043). Severe complications, Clavien grade >= IIIb, only occurred in the open group and included one postoperative death. Hospital stay was significantly shorter in the laparoscopic group than in the open group (7 vs. 12 days, p = 0.001). R0 resection was accomplished in 93.8 % of laparoscopic patients. CONCLUSION: Laparoscopic approach seems technically feasible and safe. This modern approach may optimize the surgical strategy in the future of HCC management. PMID- 27655377 TI - Self-assessment in laparoscopic surgical skills training: Is it reliable? AB - BACKGROUND: The concept of self-assessment has been widely acclaimed for its role in the professional development cycle and self-regulation. In the field of medical education, self-assessment has been most used to evaluate the cognitive knowledge of students. The complexity of training and evaluation in laparoscopic surgery has previously acted as a barrier in determining the benefits self assessment has to offer in comparison with other fields of medical education. METHODS: Thirty-five surgical residents who attended the 2-day Laparoscopic Surgical Skills Grade 1 Level 1 curriculum were invited to participate from The Netherlands, India and Romania. The competency assessment tool (CAT) for laparoscopic cholecystectomy was used for self- and expert-assessment and the resulting distributions assessed. RESULTS: A comparison between the expert- and self-assessed aggregates of scores from the CAT agreed with previous studies. Uniquely to this study, the aggregates of individual sub-categories-'use of instruments'; 'tissue handling'; and errors 'within the component tasks' and the 'end product' from both self- and expert-assessments-were investigated. There was strong positive correlation (r s > 0.5; p < 0.001) between the expert- and self assessment in all categories with only the 'tissue handling' having a weaker correlation (r s = 0.3; p = 0.04). The distribution of the mean of the differences between self-assessment and expert-assessment suggested no significant difference between the scores of experts and the residents in all categories except the 'end product' evaluation where the difference was significant (W = 119, p = 0.03). CONCLUSION: Self-assessment using the CAT form gives results that are consistently not different from expert-assessment when assessing one's proficiency in surgical skills. Areas where there was less agreement could be explained by variations in the level of training and understanding of the assessment criteria. PMID- 27655378 TI - Laparoscopic duodenoduodenostomy with parallel anastomosis for duodenal atresia. AB - BACKGROUND: Currently, a diamond-shaped anastomosis is preferred for the surgical repair of duodenal atresia (DA) in both open and laparoscopic surgery. We report the results of laparoscopic duodenoduodenostomy with parallel anastomosis (LDPA) in DA. METHODS: We retrospectively reviewed 22 patients who underwent laparoscopic duodenoduodenostomy from February 2005 to May 2015 in Samsung Medical Center. All patients underwent operation within the first month after birth. Patients who were transversely anastomosed after duodenotomy and patients who underwent simultaneous operation on combined anomalies were excluded. Parallel anastomosis was used in all surgeries. Four trocars were used in laparoscopic repair. After mobilization of both proximal and distal ends, the proximal end was incised transversely and the distal end was incised longitudinally. Duodenoduodenostomy with parallel anastomosis using a 5-0 glyconate monofilament was performed with interrupted sutures. RESULTS: Eleven patients (50 %) were male. Median gestational age was 36 + 6 weeks (32 + 7-40 + 6). Median age at the time of operation and median body weight were 3 days (1-12) and 2.53 kg (1.63-3.18), respectively. All patients were diagnosed prenatally and 16 patients (72.7 %) had associated anomalies. Median operation time was 142 min (96-290) and median postoperative day to start oral feeding was 5 days (3-9) and median postoperative day of reaching full feeding was 11 days (6-19). Median postoperative day was 13 days (10-60). There was no anastomotic leakage or stenosis. Median follow up was 3.5 months (1-21). Currently, there is no late complication. CONCLUSIONS: LDPA can be performed easily to patients who have DA in neonatal period. It is anatomically natural and the risk of leakage or stenosis does not seem significant. Therefore, parallel anastomosis should be considered as a safe procedural option for laparoscopic duodenoduodenostomy in DA. PMID- 27655379 TI - Development of an evidence-based training program for laparoscopic hysterectomy on a virtual reality simulator. AB - BACKGROUND: Substantial evidence in the scientific literature supports the use of simulation for surgical education. However, curricula lack for complex laparoscopic procedures in gynecology. The objective was to evaluate the validity of a program that reproduces key specific components of a laparoscopic hysterectomy (LH) procedure until colpotomy on a virtual reality (VR) simulator and to develop an evidence-based and stepwise training curriculum. METHODS: This prospective cohort study was conducted in a Marseille teaching hospital. Forty participants were enrolled and were divided into experienced (senior surgeons who had performed more than 100 LH; n = 8), intermediate (surgical trainees who had performed 2-10 LH; n = 8) and inexperienced (n = 24) groups. Baselines were assessed on a validated basic task. Participants were tested for the LH procedure on a high-fidelity VR simulator. Validity evidence was proposed as the ability to differentiate between the three levels of experience. Inexperienced subjects performed ten repetitions for learning curve analysis. Proficiency measures were based on experienced surgeons' performances. Outcome measures were simulator derived metrics and Objective Structured Assessment of Technical Skills (OSATS) scores. RESULTS: Quantitative analysis found significant inter-group differences between experienced intermediate and inexperienced groups for time (1369, 2385 and 3370 s; p < 0.001), number of movements (2033, 3195 and 4056; p = 0.001), path length (3390, 4526 and 5749 cm; p = 0.002), idle time (357, 654 and 747 s; p = 0.001), respect for tissue (24, 40 and 84; p = 0.01) and number of bladder injuries (0.13, 0 and 4.27; p < 0.001). Learning curves plateaued at the 2nd to 6th repetition. Further qualitative analysis found significant inter-group OSATS score differences at first repetition (22, 15 and 8, respectively; p < 0.001) and second repetition (25.5, 19.5 and 14; p < 0.001). CONCLUSIONS: The VR program for LH accrued validity evidence and allowed the development of a training curriculum using a structured scientific methodology. PMID- 27655380 TI - Transoral fundoplication offers durable symptom control for chronic GERD: 3-year report from the TEMPO randomized trial with a crossover arm. AB - BACKGROUND: Four randomized controlled trials have demonstrated the short-term efficacy and safety of transoral esophagogastric fundoplication (TF) performed with the EsophyX(r) device in eliminating troublesome gastroesophageal reflux disease (GERD) symptoms in well-selected patient populations. The aim of this study was to assess the durability of these outcomes at 3 years post-procedure. METHODS: The TF EsophyX versus Medical PPI Open Label trial was conducted in seven US sites. Between June and August 2012, we enrolled patients with small (<2 cm) or absent hiatal hernias who suffered from troublesome GERD symptoms while on PPI therapy for at least 6 months and had abnormal esophageal acid exposure (EAE). Randomization was to TF group (n = 40) or to PPI group (n = 23). Following evaluation at 6 months, all remaining PPI patients (n = 21) elected to undergo crossover to TF. Fifty-two patients were assessed at 3 years for (1) GERD symptom resolution using three GERD-specific quality of life questionnaires, (2) healing of esophagitis using endoscopy, (3) EAE using 48-h Bravo testing, and (4) discontinuation of PPI use. Two patients who underwent revisional procedures by year 3 were included in the final analysis. RESULTS: At 3-year follow-up, elimination of troublesome regurgitation and all atypical symptoms was reported by 90 % (37/41) and 88 % (42/48) of patients, respectively. The mean Reflux Symptom Index score improved from 22.2 (9.2) on PPIs at screening to 4 (7.1) off PPIs 3 years post-TF, p < 0.0001. The mean total % time pH <4 improved from 10.5 (3.5) to 7.8 (5.7), p = 0.0283. Esophagitis was healed in 86 % (19/22) of patients. At the end of study, 71 % (37/52) of patients had discontinued PPI therapy. All outcome measures remained stable between 1-, 2-, and 3-year follow ups. CONCLUSION: This study demonstrates that TF can be used to achieve long-term control of chronic GERD symptoms, healing of esophagitis, and improvement in EAE. PMID- 27655382 TI - Cost-effectiveness of a new strategy to identify uncomplicated gallstone disease patients that will benefit from a cholecystectomy. AB - BACKGROUND: The aim of this study was to determine the cost-effectiveness of a new strategy for the preoperative detection of patients that will likely benefit from a cholecystectomy, using simple criteria that can be applied by surgeons. Criteria for a cholecystectomy indication are: (1) having episodic pain; (2) onset of pain 1 year or less before the outpatient clinic visit. METHODS: The cost-effectiveness of the new strategy was evaluated against current practice using a decision analytic model. The incremental cost-effectiveness of applying criteria for a cholecystectomy for a patient with abdominal pain and gallstones was compared to applying no criteria. The incremental cost-effectiveness ratio (ICER) was expressed as extra costs to be invested to gain one more patient with absence of pain. Scenarios were analyzed to assess the influence of applying different criteria. RESULTS: The new strategy of applying one out of two criteria resulted in a 4 % higher mean proportion of patients with absence of pain compared to current practice with similar costs. The 95 % upper limit of the ICER was ?4114 ($4633) per extra patient with relief of upper abdominal pain. Application of two out of two criteria resulted in a 3 % lower mean proportion of patients with absence of pain with lower costs. CONCLUSION: The new strategy of using one out of two strict selection criteria may be an effective but also a cost-effective method to reduce the proportion of patients with pain after cholecystectomy. PMID- 27655381 TI - Using virtual reality simulation to assess competence in video-assisted thoracoscopic surgery (VATS) lobectomy. AB - BACKGROUND: The societies of thoracic surgery are working to incorporate simulation and competency-based assessment into specialty training. One challenge is the development of a simulation-based test, which can be used as an assessment tool. The study objective was to establish validity evidence for a virtual reality simulator test of a video-assisted thoracoscopic surgery (VATS) lobectomy of a right upper lobe. METHODS: Participants with varying experience in VATS lobectomy were included. They were familiarized with a virtual reality simulator (LapSim(r)) and introduced to the steps of the procedure for a VATS right upper lobe lobectomy. The participants performed two VATS lobectomies on the simulator with a 5-min break between attempts. Nineteen pre-defined simulator metrics were recorded. RESULTS: Fifty-three participants from nine different countries were included. High internal consistency was found for the metrics with Cronbach's alpha coefficient for standardized items of 0.91. Significant test-retest reliability was found for 15 of the metrics (p-values <0.05). Significant correlations between the metrics and the participants VATS lobectomy experience were identified for seven metrics (p-values <0.001), and 10 metrics showed significant differences between novices (0 VATS lobectomies performed) and experienced surgeons (>50 VATS lobectomies performed). A pass/fail level defined as approximately one standard deviation from the mean metric scores for experienced surgeons passed none of the novices (0 % false positives) and failed four of the experienced surgeons (29 % false negatives). CONCLUSION: This study is the first to establish validity evidence for a VATS right upper lobe lobectomy virtual reality simulator test. Several simulator metrics demonstrated significant differences between novices and experienced surgeons and pass/fail criteria for the test were set with acceptable consequences. This test can be used as a first step in assessing thoracic surgery trainees' VATS lobectomy competency. PMID- 27655384 TI - Anodal transcranial direct current stimulation of right temporoparietal area inhibits self-recognition. AB - Self-other discrimination is a crucial mechanism for social cognition. Neuroimaging and neurostimulation research has pointed to the involvement of the right temporoparietal region in a variety of self-other discrimination tasks. Although repetitive transcranial magnetic stimulation over the right temporoparietal area has been shown to disrupt self-other discrimination in face recognition tasks, no research has investigated the effect of increasing the cortical excitability in this region on self-other face discrimination. Here we used transcranial direct current stimulation (tDCS) to investigate changes in self-other discrimination with a video-morphing task in which the participant's face morphed into, or out of, a familiar other's face. The task was performed before and after 20 min of tDCS targeting the right temporoparietal area (anodal, cathodal, or sham stimulation). Differences in task performance following stimulation were taken to indicate a change in self-other discrimination. Following anodal stimulation only, we observed a significant increase in the amount of self-face needed to distinguish between self and other. The findings are discussed in relation to the control of self and other representations and to domain-general theories of social cognition. PMID- 27655383 TI - Laparoscopic versus robotic colectomy: a national surgical quality improvement project analysis. AB - INTRODUCTION: Robotic colorectal surgery is being increasingly adopted. Our objective was to compare early postoperative outcomes between robotic and laparoscopic colectomy in a nationally representative sample. METHODS: The American College of Surgeons National Surgical Quality Improvement Project Colectomy Targeted Dataset from 2012 to 2014 was used for this study. Adult patients undergoing elective colectomy with an anastomosis were included. Patients were stratified based on location of colorectal resection (low anterior resection (LAR), left-sided resection, or right-sided resection). Bivariate data analysis was performed, and logistic regression modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: There were a total of 25,998 laparoscopic colectomies (30 % LAR's, 45 % left-sided, and 25 % right-sided) and 1484 robotic colectomies (54 % LAR's, 28 % left-sided, and 18 % right-sided). The risk-adjusted overall morbidity, serious morbidity, and mortality were similar between laparoscopic and robotic approaches in all anastomotic groups. Patients undergoing robotic LAR had a lower conversion rate (OR 0.47, 95 % CI 1.20-1.76) and postoperative sepsis rate (OR 0.49, 95 % CI 0.29-0.85) but a higher rate of diverting ostomies (OR 1.45, 95 % CI 1.20-1.76). Robotic right-sided colectomies had significantly lower conversion rates (OR 0.58, 95 % CI 0.34-0.96). Robotic colectomy in all groups was associated with a longer operative time (by 40 min) and a decreased length of stay (by 0.5 days). CONCLUSIONS: In a nationally representative sample comparing laparoscopic and robotic colectomies, the overall morbidity, serious morbidity, and mortality between groups are similar while length of stay was shorter by 0.5 days in the robotic colectomy group. Robotic LAR was associated with lower conversion rates and lower septic complications. However, robotic LAR is also associated with a significantly higher rate of diverting ostomy. The reason for this relationship is unclear. Surgeon factors, patient factors, and technical factors should be considered in future studies. PMID- 27655385 TI - A CHASE3/GAF sensor hybrid histidine kinase BmsA modulates biofilm formation and motility in Pseudomonas alkylphenolica. AB - Pseudomonas alkylphenolica is an important strain in the biodegradation of toxic alkylphenols and mass production of bioactive polymannuronate polymers. This strain forms a diverse, 3D biofilm architecture, including mushroom-like aerial structures, circular pellicles and surface spreading, depending on culture conditions. A mutagenesis and complementation study showed that a predicted transmembrane kinase, PSAKL28_21690 (1164 aa), harbouring a periplasmic CHASE3 domain flanked by two transmembrane helices in addition to its cytoplasmic GAF, histidine kinase and three CheY-like response regulator domains, plays a positive role in the formation of the special biofilm architecture and a negative role in swimming activity. In addition, the gene, named here as bmsA, is co-transcribed with three genes encoding proteins with CheR (PSAKL28_21700) and CheB (PSAKL28_21710) domains and response regulator and histidine kinase domains (PSAKL28_21720). This gene cluster is thus named bmsABCD and is found widely distributed in pseudomonads and other bacteria. Deletion of the genes in the cluster, except forbmsA, did not result in changes in biofilm-related phenotypes. The RNA-seq analysis showed that the expression of genes coding for flagellar synthesis was increased when bmsA was mutated. In addition, the expression of rsmZ, which is one of final targets of the Gac regulon, was not significantly altered in the bmsA mutant, and overexpression of bmsA in the gacA mutant did not produce the WT phenotype. These results indicate that the sensory Bms regulon does not affect the upper cascade of the Gac signal transduction pathway for the biofilm-related phenotypes in P. alkylphenolica. PMID- 27655386 TI - Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma. AB - BACKGROUND: Patient derived xenografts (PDX) are generated by transplanting the original patient's tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. METHODS: In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. RESULTS: Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. CONCLUSION: Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC. PMID- 27655387 TI - Genetic and epigenetic analysis of schizophrenia in blood-a no-brainer? AB - Several recent studies have investigated either genetic or epigenetic variation in schizophrenia. A recent study presents comprehensive analyses of blood samples to better characterize the combined role of genetic and epigenetic variation in schizophrenia. While the paper identifies significant associations with schizophrenia risk and diagnosis, the potential relevance to the brain in schizophrenia is questionable. PMID- 27655388 TI - Medium- and Long-Term Effects of Estrogenic Contaminants on the Middle River Po Fish Community as Reconstructed from a Sediment Core. AB - Recent studies showed that endocrine active compounds (EDs) capable to induce fish gonadal histopathologies, plasma vitellogenin and thyroid disruption, are transported by the River Lambro to the River Po, potentially affecting the fish community of the main Italian river. To assess whether fish relative abundance, composition and health were impaired by the River Lambro, a 3-year survey was undertaken in the main river. Results showed that the tributary supports in the River Po a denser fish community (+43 %), with a higher total biomass (+35 %). The survey also showed niche- and sensitivity-dependent effects, so that three benthopelagic species (bleak, topmouth gudgeon, and bitterling) were, for example, more abundant downstream from the tributary (up to 3.4*), but their sizes were significantly smaller. The present fish community was then compared with that described 30 years before in the same area of the Po River. This comparison highlighted that some fish species have disappeared and many have severely declined. To better evaluate this contrast, a sediment core of the Lambro tributary was analysed for the time trends of natural estrogens (E1, E2, E3), bisphenol A and alkylphenols. The results showed that during the last 50 years the River Lambro has been exposed to high estrogenic activities (16.1 +/- 9.3 ng E2 equivalents/g), which inevitably affected also the River Po. In addition, at the time of the previous survey, six species of the main river had skewed sex ratios toward all-female populations, providing evidence that EDs and particularly (xeno)estrogens were already affecting the long-term viability of fish populations. Estrogens thus can be ascribed among the causal factors of fish qualitative and quantitative decline of the River Po, although long-term effects have been likely mitigated by nonconfinement of fish populations and nutrient enrichment. PMID- 27655389 TI - Testicular histology may predict the successful sperm retrieval in patients with non-obstructive azoospermia undergoing conventional TESE: a diagnostic accuracy study. AB - PURPOSE: The present study sought to determine the diagnostic accuracy of FSH level, testicular volume, and testicular histology in predicting the successful sperm retrieval (SSR) in a large cohort of patients with non-obstructive azoospermia undergoing conventional testicular sperm extraction (TESE). METHODS: We retrospectively evaluated 356 patients with non-obstructive azoospermia between June 2004 and July 2009. Binary logistic regression was used to evaluate the diagnostic accuracy of our predicting model, identifying sperm retrieval rate as binary dependent variable. The predictive accuracy of all variables individually evaluated was quantified with area under curve (AUC) estimates derived from receiver operating characteristic (ROC) curve. RESULTS: The mean patients' age was 36.8 years. Testicular sperm were retrieved in 158 out of 356 patients (44.3 %). Histological diagnosis of Sertoli cell only syndrome (SCO) was obtained in 216 patients (60.6 %), while 55 patients (15.4 %) had maturation arrest (MA) and 85 (23.8 %) had hypospermatogenesis (HYPO). The binary logistic regression model was statistically significant (chi 2 = 96.792, p < 0.0001) and correctly classified 72.8 % of cases with 46.8 % sensitivity and 93.4 % specificity, positive predictive value (PPV) 85.06 %, negative predictive value (NPV) 68.7 %, +likelihood ratio (LR) 7.13, and -LR 0.57. Only testicular histology was significant to the model, while FSH and testicular volume were not. Sperm retrieval rate (SRR) was significantly higher in patients with HYPO compared to patients with SCO or MA (88.2 vs 30.5 and 30.9 %, respectively, p < 0.0001) CONCLUSIONS: This study demonstrates that including testicular histology in a model for predicting sperm retrieval increases its diagnostic accuracy. As histology is not available prior to TESE, this model applies only to patients with previous testicular surgery. PMID- 27655390 TI - Altered bivalent positioning in metaphase I human spermatocytes from Robertsonian translocation carriers. AB - PURPOSE: The study aims to determine whether there is an altered bivalent positioning in metaphase I human spermatocytes from Robertsonian translocation carriers. METHODS: Metaphase I human spermatocytes from three 45,XY,der(13;14)(q10;q10) individuals and a 45,XY,der(14;15)(q10;q10) individual were analyzed. Proximity relationships of bivalents were established by analyzing meiotic preparations combining Leishman staining and multiplex-FISH procedures. Poisson regression model was used to determine proximity frequencies between bivalents and to assess associations with chromosome size, gene density, acrocentric morphology, and chromosomes with heterochromatic blocks. The hierarchical cluster Ward method was used to characterize the groups of bivalents with preferred proximities in a cluster analysis. Bivalent groups obtained were individually compared with those obtained in normal karyotype individuals evaluated in a previous study. RESULTS: A total of 1288 bivalents were examined, giving a total of 2289 proximity data. Only four positive significant proximities were detected for each type of Robertsonian translocation. Significant bivalent associations were only observed by small-size chromosomes for MI,22,XY,III(13q14q). These results were clearly divergent from 46,XY individuals. Moreover, cluster analysis revealed that about 30 % of the bivalents showed changes in their proximity relationships in metaphase I. CONCLUSIONS: The territorial organization of bivalents in metaphase I human spermatocytes changes in the presence of a Robertsonian translocation. PMID- 27655393 TI - Editorial (Thematic Issue: Current Research on Cannabis Use Disorder). PMID- 27655394 TI - Editorial: Measurements of ABC Transporters at the Blood-Brain Barrier: Novel Methods and Applications. PMID- 27655391 TI - Prevention of Early Substance Use Mediates, and Variation at SLC6A4 Moderates, SAAF Intervention Effects on OXTR Methylation. AB - The Strong African American Family (SAAF) program has been shown to have a variety of short and long-term benefits for participating youth and families. However, biological mechanisms potentially influencing long-term effects on resilience in young adulthood have not been examined. In the current investigation, we examine the effects of SAAF on methylation of the OXTR gene in young adulthood, focusing on a regulatory region previously identified to be both responsive to stress and implicated in resilience. Using the subsample of participants from the original study for whom methylation data was available (N = 388), we replicated the previously reported G * E effect on prevention of early substance use and then examined whether there would also be a moderated effect on OXTR methylation in early adulthood, with "s" allele carriers, but not "LL" participants, showing a significant indirect effect of SAAF on OXTR methylation. Results suggest that for susceptible youth (i.e., "s" allele carriers), preventive intervention may "get under the skin," in a manner potentially beneficial for long-term outcomes. Implications for examination of OXTR methylation in future prevention research are discussed. PMID- 27655392 TI - Association between pathologic features of peripheral nerves and postoperative anal function after neoadjuvant therapy for low rectal cancer. AB - PURPOSE: Neoadjuvant chemoradiotherapy (CRT) for rectal cancer improves local control but also induces severe postoperative anal dysfunction that may be related to neural degeneration. The aims of the study were to identify pathological features of neural degeneration caused by neoadjuvant CRT or neoadjuvant chemotherapy (NAC) and to evaluate the association between neural degeneration and anal function. METHODS: A retrospective study using chronologically different groups was performed in 95 patients with rectal cancer treated with curative resection with neoadjuvant CRT (n = 47), NAC (n = 27), or surgery alone (no neoadjuvant therapy) (n = 21) at National Cancer Center Hospital East from 2001 to 2014. Peripheral nerve degeneration was evaluated histopathologically using H&E stained sections, based on karyopyknosis, vacuolar or acidophilic degeneration, denucleation, adventitial neuron change, and fibrosis. Morphological analysis of peripheral nerves was compared among the three groups. The association between pathological features and anal function (Wexner Score) was evaluated. RESULTS: After CRT, the degree of fibrosis around the tumor was severe, and neural degeneration was found in peripheral neurons. With NAC and surgery alone, there was little fibrosis and neural degeneration. Pathological changes after CRT were more pronounced than those after NAC, indicating greater tissue degeneration due to CRT. There was an association between anal function and degeneration score in the CRT group, but not in the other groups. CONCLUSIONS: Peripheral nerves in patients who received neoadjuvant CRT showed characteristic pathological features indicating greater degeneration, compared with patients who received NAC. Neural degeneration is associated with anal function and several pathological factors after CRT. PMID- 27655396 TI - Rotenone Decreases Hatching Success in Brine Shrimp Embryos by Blocking Development: Implications for Zooplankton Egg Banks. AB - While many zooplankton species recover quickly after the treatment of water resources with the piscicide, rotenone, some fail to reach pretreatment population density or, in rare cases, do not reappear at all. The variable impact of rotenone on zooplankton populations could stem from differences in the capacity of species to switch entirely to anaerobic catabolic pathways in the presence of rotenone, which blocks mitochondrial electron transport. Alternatively, variable responses among species could originate from differences in permeability of dormant life-stages to lipophilic chemicals like rotenone. The purpose of the present study was to determine the effects of rotenone on development, emergence and hatching of zooplankton embryos that lack both the anaerobic capacity to develop in the presence of rotenone and a permeability barrier to prevent the entry of rotenone during dormancy. Post-diapause embryos of the brine shrimp, Artemia franciscana, were employed as a model system, because they are permeable to lipophilic compounds when dechorionated and require aerobic conditions to support development. Early development in this species is also well characterized in the literature. Brine shrimp embryos were exposed to rotenone while development was either slowed by chilling or suspended by anoxia. Development, emergence and hatching were then observed in rotenone-free artificial seawater. The data presented demonstrate that rotenone freely diffuses across the embryonic cuticle in a matter of hours, and prevents development and emergence after brief exposures to ecologically relevant concentrations (0.025 0.5 mg L-1) of the piscicide. Neither the removal of rotenone from the environment, nor the removal of embryonic water with a hypertonic solution, are sufficient to reverse this block on development and emergence. These data indicate that rotenone could impair recruitment from egg banks for species of zooplankton that lack both an embryonic barrier to the entry of lipophilic compounds and the anaerobic capacity to develop when NADH:ubiquinone oxidoreductase activity is inhibited by rotenone. PMID- 27655397 TI - RING box protein-1 gene involved in flagellar disassembly of Dunaliella salina. AB - Ring box protein-1 (RBX1), also called Regulator of Cullins-1 (ROC1), is a key component of SCF (Skp-1, cullins, F-box proteins) E3 ubiquitin ligases, which regulate diverse cellular processes by targeting protein substrates for degradation. Although RBX1 plays an important role in ubiquitination machinery of both prokaryotes and eukaryotes, studies on the RBX1 have not been involved in the unicellular green alga Dunaliella salina. In this study, a full-length RBX1 cDNA fragment of 817 bp was cloned using rapid amplification of cDNA end (RACE) technique. The full-length sequence contained an open reading frame of 411 bp encoding 136 amino acids. The predicted protein had a molecular molar mass of 14.8 kDa and pI of 5.9 with a high degree of homology to RBX1 from Chlamydomonas reinhardtii (92 %). Recombinant RBX1 was expressed in Escherichia coli BL21 and was purified and characterized. The apparent molecular mass of the recombinant protein was approximately 17 kDa, and the optimal induction time and concentration were 3 h and 0.1 mmol/L IPTG, respectively. The predicted 3D structures of RBX1 proteins contained RING-H2 finger domain including "Cys59-X2 Cys62-X30-Cys93-X1-His95-X2-His98-X2-Cys101-X10-Cys112-X2-Cys115." The expression of RBX1 protein was increased by 132 % during flagellar disassembly and decreased by 76 % during flagellar assembly of D. salina. The expression of RBX1 mRNA had a similar tendency with the expression of RBX1 protein. The results indicated that RBX1 responded to flagellar disassembly of D. salina. PMID- 27655398 TI - Measuring customer preferences in the German statutory health insurance. AB - This paper investigates consumer preferences in the German statutory health insurance market. It further aims to test whether preferences differ by age and health status. Evidence is provided by a discrete choice experiment conducted in 2014 using the six most important attributes in sickness fund competition and ten random generated choice sets per participant. Price is found to be the most important attribute followed by additional benefits, managed care programmes, and distance to nearest branch. Other positive attributes of sickness funds are found to balance out a higher price, which would allow a sickness fund to position itself as high quality. However, significant differences in preferences were found between age and health status group. In particular, compromised health is associated with higher preference for illness-related additional benefits and less distance to the lowest branch, but lower preference for a lower price. Based on these differences, a distinct sickness fund offer could be constructed that would allow passive risk selection. PMID- 27655399 TI - Microbial Characterization of Qatari Barchan Sand Dunes. AB - This study represents the first characterization of sand microbiota in migrating barchan sand dunes. Bacterial communities were studied through direct counts and cultivation, as well as 16S rRNA gene and metagenomic sequence analysis to gain an understanding of microbial abundance, diversity, and potential metabolic capabilities. Direct on-grain cell counts gave an average of 5.3 +/- 0.4 x 105 cells g-1 of sand. Cultured isolates (N = 64) selected for 16S rRNA gene sequencing belonged to the phyla Actinobacteria (58%), Firmicutes (27%) and Proteobacteria (15%). Deep-sequencing of 16S rRNA gene amplicons from 18 dunes demonstrated a high relative abundance of Proteobacteria, particularly enteric bacteria, and a dune-specific-pattern of bacterial community composition that correlated with dune size. Shotgun metagenome sequences of two representative dunes were analyzed and found to have similar relative bacterial abundance, though the relative abundances of eukaryotic, viral and enterobacterial sequences were greater in sand from the dune closer to a camel-pen. Functional analysis revealed patterns similar to those observed in desert soils; however, the increased relative abundance of genes encoding sporulation and dormancy are consistent with the dune microbiome being well-adapted to the exceptionally hyper arid Qatari desert. PMID- 27655400 TI - Bacterial persistence is an active sigmaS stress response to metabolic flux limitation. AB - While persisters are a health threat due to their transient antibiotic tolerance, little is known about their phenotype and what actually causes persistence. Using a new method for persister generation and high-throughput methods, we comprehensively mapped the molecular phenotype of Escherichia coli during the entry and in the state of persistence in nutrient-rich conditions. The persister proteome is characterized by sigma(S)-mediated stress response and a shift to catabolism, a proteome that starved cells tried to but could not reach due to absence of a carbon and energy source. Metabolism of persisters is geared toward energy production, with depleted metabolite pools. We developed and experimentally verified a model, in which persistence is established through a system-level feedback: Strong perturbations of metabolic homeostasis cause metabolic fluxes to collapse, prohibiting adjustments toward restoring homeostasis. This vicious cycle is stabilized and modulated by high ppGpp levels, toxin/anti-toxin systems, and the sigma(S)-mediated stress response. Our system level model consistently integrates past findings with our new data, thereby providing an important basis for future research on persisters. PMID- 27655405 TI - Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort. AB - BACKGROUND: Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis. METHODS: We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified. RESULTS: Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 - 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 - 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 - 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved. CONCLUSIONS: Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke. PMID- 27655403 TI - Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice. AB - Neuronopathic Gaucher disease (nGD) manifests as severe neurological symptoms in patients with no effective treatment available. Ryanodine receptors (Ryrs) are a family of calcium release channels on intracellular stores. The goal of this study is to determine if Ryrs are potential targets for nGD treatment. A nGD cell model (CBE-N2a) was created by inhibiting acid beta-glucosidase (GCase) in N2a cells with conduritol B epoxide (CBE). Enhanced cytosolic calcium in CBE-N2a cells was blocked by either ryanodine or dantrolene, antagonists of Ryrs and by Genz-161, a glucosylceramide synthase inhibitor, suggesting substrate-mediated ER calcium efflux occurs through ryanodine receptors. In the brain of a nGD (4L;C*) mouse model, expression of Ryrs was normal at 13 days of age, but significantly decreased below the wild type level in end-stage 4L;C* brains at 40 days. Treatment with dantrolene in 4L;C* mice starting at postnatal day 5 delayed neurological pathology and prolonged survival. Compared to untreated 4L;C* mice, dantrolene treatment significantly improved gait, reduced LC3-II levels, improved mitochondrial ATP production and reduced inflammation in the brain. Dantrolene treatment partially normalized Ryr expression and its potential regulators, CAMK IV and calmodulin. Furthermore, dantrolene treatment increased residual mutant GCase activity in 4L;C* brains. These data demonstrate that modulating Ryrs has neuroprotective effects in nGD through mechanisms that protect the mitochondria, autophagy, Ryr expression and enhance GCase activity. This study suggests that calcium signalling stabilization, e.g. with dantrolene, could be a potential disease modifying therapy for nGD. PMID- 27655406 TI - Preparedness of HIV care and treatment clinics for the management of concomitant non-communicable diseases: a cross-sectional survey. AB - BACKGROUND: In Sub-Saharan Africa, epidemiological studies have reported an increasing burden of non-communicable diseases (NCD) among people living with HIV. NCD management can be feasibly integrated into HIV care; however, clinic readiness to provide NCD services in these settings should first be assessed and gaps in care identified. METHODS: A cross-sectional survey conducted in July 2013 assessed the resources available for NCD care at 14 HIV clinics in Dar es Salaam, Tanzania. Survey items related to staff training, protocols, and resources for cardiovascular disease risk factor screening, management, and patient education. RESULTS: 43 % of clinics reported treating patients with hypertension; however, only 21 % had a protocol for NCD management. ECHO International Health standards for essential clinical equipment were used to measure clinic readiness; 36 % met the standard for blood pressure cuffs, 14 % for glucometers. Available laboratory tests for NCD included blood glucose (88 %), urine dipsticks (78 %), and lipid panel (57 %). 21 % had a healthcare worker with NCD training. All facilities provided some form of patient education, but only 14 % included diabetes, 57 % tobacco cessation, and 64 % weight management. CONCLUSIONS: A number of gaps were identified in this sample of HIV clinics that currently limit the ability of Tanzanian healthcare workers to diagnose and manage NCD in the context of HIV care. Integrated NCD and HIV care may be successfully achieved in these settings with basic measures incorporated into existing infrastructures at minimal added expense, i.e., improving access to basic functioning equipment, introducing standardized treatment guidelines, and improving healthcare worker education. PMID- 27655407 TI - Characterization of the transcription factor encoding gene, KlADR1: metabolic role in Kluyveromyces lactis and expression in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, Adr1 is a zinc-finger transcription factor involved in the transcriptional activation of ADH2. Deletion of KlADR1, its putative ortholog in Kluyveromyces lactis, led to reduced growth in glycerol, oleate and yeast extract-peptone medium suggesting, as in S. cerevisiae, its requirement for glycerol, fatty acid and nitrogen utilization. Moreover, growth comparison on yeast extract and peptone plates showed in K. lactis a KlAdr1-dependent growth trait not present in S. cerevisiae, indicating different metabolic roles of the two factors in their environmental niches. KlADR1 is required for growth under respiratory and fermentative conditions like KlADH, alcohol dehydrogenase genes necessary for metabolic adaptation during the growth transition. Using in-gel native alcohol dehydrogenase assay, we showed that this factor affected the Adh pattern by altering the balance between these activities. Since the activity most affected by KlAdr1 is KlAdh3, a deletion analysis of the KlADH3 promoter allowed the isolation of a DNA fragment through which KlAdr1 modulated its expression. The expression of the KlADR1-GFP gene allowed the intracellular localization of the factor in K. lactis and S. cerevisiae, suggesting in the two yeasts a common mechanism of KlAdr1 translocation under fermentative and respiratory conditions. Finally, the chimeric Kl/ScADR1 gene encoding the zinc-finger domains of KlAdr1 fused to the transactivating domains of the S. cerevisiae factor activated in Scadr1Delta the transcription of ADH2 in a ScAdr1-dependent fashion. PMID- 27655409 TI - [Integration and utilization of physiotherapy in hospice and palliative care : A survey on clinical practice in Germany]. AB - BACKGROUND: Palliative care is an approach that improves the quality of life of patients with incurable and progressive illnesses; therefore, in these situations physiotherapy can play an important role. AIM: This study was carried out to examine the integration and utilization of physiotherapy in palliative and hospice care services in Germany. METHODS: A cross-sectional survey including all palliative care units, specialized outpatient palliative care teams and hospices in Germany (n = 680) in 2013 was carried out. RESULTS: The response rate was 43.5 % (n = 296). Physiotherapy is predominantly applied in palliative care units (79 %) but rarely in hospices (38 %) and outpatient palliative care teams (30 %). A structured physiotherapeutic assessment is rarely carried out even on palliative care units (26 %). Positive effects of physiotherapy are especially described for symptoms, such as edema, pain, constipation and dyspnea. CONCLUSION: Despite its significant potential to relieve symptoms, physiotherapy is not systematically integrated into palliative care practice in Germany. PMID- 27655408 TI - SES Gradients Among Mexicans in the United States and in Mexico: A New Twist to the Hispanic Paradox? AB - : Recent empirical findings have suggested the existence of a twist in the Hispanic paradox, in which Mexican and other Hispanic foreign-born migrants living in the United States experience shallower socioeconomic status (SES) health disparities than those in the U.S. POPULATION: In this article, we seek to replicate this finding and test conjectures that could explain this new observed phenomenon using objective indicators of adult health by educational attainment in several groups: (1) Mexican-born individuals living in Mexico and in the United States, (2) U.S.-born Mexican Americans, and (3) non-Hispanic American whites. Our analytical strategy improves upon previous research on three fronts. First, we derive four hypotheses from a general framework that has also been used to explain the standard Hispanic paradox. Second, we study biomarkers rather than self-reported health and related conditions. Third, we use a binational data platform that includes both Mexicans living in Mexico (Mexican National Health and Nutrition Survey 2006) and Mexican migrants to the United States (NHANES 1999 2010). We find steep education gradients among Mexicans living in Mexico's urban areas in five of six biomarkers of metabolic syndrome (MetS) and in the overall MetS score. Mexican migrants living in the United States experience similar patterns to Mexicans living in Mexico in glucose and obesity biomarkers. These results are inconsistent with previous findings, suggesting that Mexican migrants in the United States experience significantly attenuated health gradients relative to the non-Hispanic white U.S. POPULATION: Our empirical evidence also contradicts the idea that SES-health gradients in Mexico are shallower than those in the United States and could be invoked to explain shallower gradients among Mexicans living in the United States. PMID- 27655410 TI - NT1014, a novel biguanide, inhibits ovarian cancer growth in vitro and in vivo. AB - BACKGROUND: NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific transporters, OCT1 and OCT3. We sought to determine the anti-tumorigenic effects of NT1014 in human ovarian cancer cell lines as well as in a genetically engineered mouse model of high-grade serous ovarian cancer. METHODS: The effects of NT1014 and metformin on cell proliferation were assessed by MTT assay using the human ovarian cancer cell lines, SKOV3 and IGROV1, as well as in primary cultures. In addition, the impact of NT1014 on cell cycle progression, apoptosis, cellular stress, adhesion, invasion, glycolysis, and AMPK activation/mTOR pathway inhibition was also explored. The effects of NT1014 treatment in vivo was evaluated using the K18 - gT121+/-; p53fl/fl; Brca1fl/fl (KpB) mouse model of high-grade serous ovarian cancer. RESULTS: NT1014 significantly inhibited cell proliferation in both ovarian cancer cell lines as well as in primary cultures. In addition, NT1014 activated AMPK, inhibited downstream targets of the mTOR pathway, induced G1 cell cycle arrest/apoptosis/cellular stress, altered glycolysis, and reduced invasion/adhesion. Similar to its anti-tumorigenic effects in vitro, NT1014 decreased ovarian cancer growth in the KpB mouse model of ovarian cancer. NT1014 appeared to be more potent than metformin in both our in vitro and in vivo studies. CONCLUSIONS: NT1014 inhibited ovarian cancer cell growth in vitro and in vivo, with greater efficacy than the traditional biguanide, metformin. These results support further development of NT1014 as a useful therapeutic approach for the treatment of ovarian cancer. PMID- 27655411 TI - The risk of hospitalized infection following initiation of biologic agents versus methotrexate in the treatment of juvenile idiopathic arthritis. AB - BACKGROUND: In the present study, we compared the incidence of hospitalized infection among children with juvenile idiopathic arthritis (JIA) following initiation of treatment with biologic agents versus methotrexate (MTX). METHODS: We used national Medicaid claims data from 2000 through 2010 to create cohorts of children with JIA who were new users of tumor necrosis factor inhibitors (TNFi), anakinra, and MTX (without concurrent biologic agent use) as defined by a 6-month baseline period of nonuse. Because most anakinra users have systemic juvenile idiopathic arthritis (SJIA), we used claims to identify MTX users who likely had SJIA. Among TNFi users, concurrent MTX use was a time-varying covariate. The study outcome was a primary hospital discharge diagnosis of infection. We calculated adjusted hazard ratios (aHRs) to compare infection rates between biologic agents and MTX. RESULTS: We identified 3075 new MTX users (160 with SJIA), 2713 new TNFi users, and 247 new anakinra users. There was no increased risk of infection associated with TNFi monotherapy versus MTX (aHR 1.19, 95 % CI 0.72-1.94) or with TNFi + MTX combination therapy versus MTX (aHR 1.23, 95 % CI 0.69-2.17). Baseline high-dose oral glucocorticoid use (>=10 mg/day of prednisone) was associated with infection (aHR 2.03 [95 % CI 1.21-3.39] versus no oral glucocorticoid). Anakinra was associated with infection versus MTX (aHR 3.53 95 % CI 1.83-6.82), but less so compared with MTX users with SJIA (aHR 2.69, 95 % CI 0.82-8.82). CONCLUSIONS: Neither TNFi monotherapy nor TNFi + MTX combination therapy was significantly associated with hospitalized infection compared with MTX. Anakinra was significantly associated with infection, but there was likely residual confounding by disease phenotype. PMID- 27655412 TI - Predicting bioactive conformations and binding modes of macrocycles. AB - Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds. PMID- 27655413 TI - Speckle-Tracking Echocardiographic Measures of Right Ventricular Diastolic Function Correlate with Reference Standard Measures Before and After Preload Alteration in Children. AB - The accuracy of echocardiographic measures of right ventricular (RV) diastolic function has been sparsely studied. Our objective was to evaluate the correlation between echocardiographic and reference standard measures of RV diastolic function derived from micromanometer pressure analysis before and after preload alteration in children. Echocardiograms and micromanometer pressure analyses were prospectively performed before and after fluid bolus in children undergoing right heart catheterization. The isovolumic relaxation time constant (tau) and end diastolic pressure (EDP) were measured. Conventional and speckle-tracking echocardiographic (STE) parameters of RV systolic and diastolic function were assessed. Normal saline bolus was given to increase RV EDP by 20 %. Twenty-eight studies were performed in 22 patients with congenital heart disease or postheart transplantation. Mean age was 8.7 +/- 6.1 years. RV longitudinal early diastolic strain rate (EDSR) correlated with tau before (r = 0.57, p = 0.001) and after fluid bolus (r = 0.48, p = 0.008). No conventional echocardiographic measures correlated with tau both before and after fluid bolus. Multiple regression analysis revealed RV EDSR and LV circumferential EDSR as independent predictors of RV tau. There were no independent predictors of EDP. RV EDSR appears to correlate with the reference standard measure of early active ventricular relaxation in children at baseline and after changes in preload. Conventional echocardiographic measures of diastolic function were not predictive of diastolic function after preload alteration. Future studies should assess the prognostic significance of STE measures of diastolic function in this population. PMID- 27655415 TI - New Advances in the Study of IgE Drug Recognition. AB - Allergic drug reactions are currently a major public health problem affecting patient health and increasing healthcare costs. They are caused by interactions between a drug and the human immune system and result in symptoms ranging from urticaria or angioedema to those more serious such as anaphylaxis or anaphylactic shock. The most commonly accepted mechanism for immunological activation is based on the hapten hypothesis. Drugs are low molecular weight substances that cannot cause an immune response on their own. However, they can act as haptens and form covalent adducts with proteins. The resulting hapten-carrier (drug-protein) conjugate can induce the production of IgE antibodies or T cells. An epitope, or antigenic determinant, is the part of the drug-protein antigen that is specifically recognized by the immune system. This may involve not only the drug derivative but also part of the carrier protein. Understanding the way in which drugs are metabolized after protein conjugation is vital in order to make progresses in the diagnosis of clinical allergy. In this review, recent advances in the identification of the chemical structures of antigenic determinants involved in immediate allergic reactions to drugs are presented. We have focused on drugs that most commonly elicit these reactions: betalactam and quinolone antibiotics and the non-steroidal anti-inflamatory drug pyrazolone. This will be discussed from a chemical point of view, relating our understanding of drug structure, chemical reactivity and immune recognition. PMID- 27655416 TI - The Synthetic Cannabinoids Phenomenon. AB - " Spice " is generally used to describe the diverse types of herbal blends that encompass synthetic cannabinoids on the market. The emergence of smokable herbal products containing synthetic cannabinoids, which mimic the effects of cannabis, appears to become increasingly popular, in the new psychoactive substances landscape. In 2014, the existence of 134 different types of synthetic cannabinoids were reported by the European Union Early Warning System. These drugs are mainly sold online as an alternative to controlled and regulated psychoactive substances. They appear to have a life cycle of about 1-2 years before being replaced by a next wave of products. Legislation controlling these designer drugs has been introduced in many countries with the objective to limit the spread of existing drugs and control potential new analogs. The majority of the synthetic cannabinoids are full agonists at the CB1 receptor and do not contain tobacco or cannabis. They are becoming increasingly popular in adolescents, students and clubbers as an abused substance. Relatively high incidence of adverse effects associated with synthetic cannabinoids use has been documented in the literature. Numerous fatalities linked with their use and abuse have been reported. In this paper, we will review the available data regarding the use and effects of synthetic cannabinoids in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were: "synthetic cannabinoids", "spice", "new psychoactive substances", and/or "substance use disorder", and/or "adverse effects", and/or "fatalities". The search was limited to years 2005 to 2016 due to emerging scientific literature at this period Health professionals should take into account that limited scientific evidence is available regarding the effect of synthetic cannabinoids use in humans. It thus urges to launch more systematic epidemiological studies, to develop and validate screening procedures, and to investigate the neurobiological and psychological correlates and risk factors associated to synthetic cannabinoids use and misuse. PMID- 27655414 TI - Engineered Autonomous Human Variable Domains. AB - BACKGROUND: The complex multi-chain architecture of antibodies has spurred interest in smaller derivatives that retain specificity but can be more easily produced in bacteria. Domain antibodies consisting of single variable domains are the smallest antibody fragments and have been shown to possess enhanced ability to target epitopes that are difficult to access using multidomain antibodies. However, in contrast to natural camelid antibody domains, human variable domains typically suffer from low stability and high propensity to aggregate. METHODS: This review summarizes strategies to improve the biophysical properties of heavy chain variable domains from human antibodies with an emphasis on aggregation resistance. Several protein engineering approaches have targeted antibody frameworks and complementarity determining regions to stabilize the native state and prevent aggregation of the denatured state. CONCLUSION: Recent findings enable the construction of highly diverse libraries enriched in aggregation resistant variants that are expected to provide binders to diverse antigens. Engineered domain antibodies possess unique advantages in expression, epitope preference and flexibility of formatting over conventional immunoreagents and are a promising class of antibody fragments for biomedical development. PMID- 27655417 TI - Comparison of Two Cap Thickness in Small Incision Lenticule Extraction: 100MUm versus 160MUm. AB - PURPOSE: To compare the changes of biomechanical properties, endothelial cell density (ECD), and posterior corneal elevation (PCE) after femtosecond small incision lenticule extractions (SMILEs) with 100MUm versus 160MUm cap thicknesses. METHODS: A total of 12 rabbits were randomly assigned into two groups of 6 each. SMILE was performed at a depth of either 160MUm (160-cap group) or 100MUm (100-cap group). Corneal biomechanics, PCE, ECD were evaluated pre operatively, 1week, 1 month, 2 months, 3 months, and 4 months post-operatively by Pentacam, Corvis ST, in vivo confocal microscopy (IVCM) respectively. The Young's modulus was obtained by strip-extensometry test 4 months after surgery. RESULTS: At each time point, the second applanation time (A2T) was similar between the groups with the exception of 4 months after surgery (22.66+/-0.16 ms in the 160 cap group versus 21.75+/-0.29 ms in the 100-cap group, p = 0.004). Neither deformation amplitude (DA) nor the first applanationtime (A1T) were significantly different between the two groups. The postoperative posterior surface did not shift forward, the changes of PCE and ECD were not significantly different between the two groups at any observation time. Young's modulus was higher in the 160-cap group than that in the 100-cap group with no statistical significance (P>0.05). Regression analyses showed that the PCE changes and Young's modulus were not affected by cap thickness (CT) or residual stromal bed thickness (RBT) (All P>0.05). CONCLUSIONS: The differences of corneal biomechanics, posterior surface elevation, or ECD changes were quite small when using 100MUm or 160MUm cap thicknesses in SMILE. PMID- 27655419 TI - Simulation of intracellular Ca2+ transients in osteoblasts induced by fluid shear stress and its application. AB - Intracellular [Formula: see text] transient induced by fluid shear stress (FSS) plays an important role in mechanical regulation of osteoblasts, but the cellular mechanism remains incompletely understood. Here, we constructed a mathematical model combined with experiments to elucidate it. Our simulated and experimental results showed that it was the delay of membrane potential repolarization to produce the refractory period of FSS-induced intracellular calcium transients in osteoblasts. Moreover, the results also demonstrated that the amplitude of FSS induced intracellular calcium transient is crucial to the proliferation, while its duration is critical to the differentiation, of osteoblasts. Overall, the present study provides a way to understand the cellular mechanism of intracellular calcium transients in osteoblast induced by FSS and explains some of related physiological events. PMID- 27655418 TI - Bone Regeneration Using Gene-Activated Matrices. AB - Gene delivery to bone is a potential therapeutic strategy for directed, sustained, and regulated protein expression. Tissue engineering strategies for bone regeneration include delivery of proteins, genes (viral and non-viral mediated delivery), and/or cells to the bone defect site. In addition, biomimetic scaffolds and scaffolds incorporating bone anabolic agents greatly enhance the bone repair process. Regional gene therapy has the potential of enhancing bone defect healing and bone regeneration by delivering osteogenic genes locally to the osseous lesions, thereby reducing systemic toxicity and the need for using supraphysiological dosages of therapeutic proteins. By implanting gene-activated matrices (GAMs), sustained gene expression and continuous osteogenic protein production in situ can be achieved in a way that stimulates osteogenesis and bone repair within osseous defects. Critical parameters substantially affecting the therapeutic efficacy of gene therapy include the choice of osteogenic transgene(s), selection of non-viral or viral vectors, the wound environment, and the selection of ex vivo and in vivo gene delivery strategies, such as GAMs. It is critical for gene therapy applications that clinically beneficial amounts of proteins are synthesized endogenously within and around the lesion in a sustained manner. It is therefore necessary that reliable and reproducible methods of gene delivery be developed and tested for their efficacy and safety before translating into clinical practice. Practical considerations such as the age, gender, and systemic health of patients and the nature of the disease process also need to be taken into account in order to personalize the treatments and progress towards developing a clinically applicable gene therapy for healing bone defects. This review discusses tissue engineering strategies to regenerate bone with specific focus on non-viral gene delivery systems. PMID- 27655420 TI - Inferring spatial variations of microstructural properties from macroscopic mechanical response. AB - Disease alters tissue microstructure, which in turn affects the macroscopic mechanical properties of tissue. In elasticity imaging, the macroscopic response is measured and is used to infer the spatial distribution of the elastic constitutive parameters. When an empirical constitutive model is used, these parameters cannot be linked to the microstructure. However, when the constitutive model is derived from a microstructural representation of the material, it allows for the possibility of inferring the local averages of the spatial distribution of the microstructural parameters. This idea forms the basis of this study. In particular, we first derive a constitutive model by homogenizing the mechanical response of a network of elastic, tortuous fibers. Thereafter, we use this model in an inverse problem to determine the spatial distribution of the microstructural parameters. We solve the inverse problem as a constrained minimization problem and develop efficient methods for solving it. We apply these methods to displacement fields obtained by deforming gelatin-agar co-gels and determine the spatial distribution of agar concentration and fiber tortuosity, thereby demonstrating that it is possible to image local averages of microstructural parameters from macroscopic measurements of deformation. PMID- 27655421 TI - Generalized plasma skimming model for cells and drug carriers in the microvasculature. AB - In microvascular transport, where both blood and drug carriers are involved, plasma skimming has a key role on changing hematocrit level and drug carrier concentration in capillary beds after continuous vessel bifurcation in the microvasculature. While there have been numerous studies on modeling the plasma skimming of blood, previous works lacked in consideration of its interaction with drug carriers. In this paper, a generalized plasma skimming model is suggested to predict the redistributions of both the cells and drug carriers at each bifurcation. In order to examine its applicability, this new model was applied on a single bifurcation system to predict the redistribution of red blood cells and drug carriers. Furthermore, this model was tested at microvascular network level under different plasma skimming conditions for predicting the concentration of drug carriers. Based on these results, the applicability of this generalized plasma skimming model is fully discussed and future works along with the model's limitations are summarized. PMID- 27655422 TI - Model-based cardiovascular disease diagnosis: a preliminary in-silico study. AB - In this study, we developed and examined the feasibility of a model-based system identification approach to cardiovascular disease diagnosis. The basic premise of the approach is that it may be possible to diagnose cardiovascular disease from disease-induced alterations in the arterial mechanical properties manifested in the proximal and distal arterial blood pressure waveforms. It first individualizes the lumped-parameter model of wave propagation and reflection in the artery using the measurement of proximal and distal arterial blood pressure waveforms. Then, it employs a diagnosis logic, in the form of disease-specific patterns in model parameters, referred as [Formula: see text] and pulse transit time. The longitudinal change in these parameters is used to diagnose the presence of peripheral artery disease and arterial stiffening. We illustrated the feasibility of the proposed approach by testing it in a full-scale in-silico arterial tree simulation. The results showed that the approach exhibited superior sensitivity to ankle-brachial index and convenience to carotid-femoral pulse wave velocity: The model parameters [Formula: see text] and [Formula: see text] responded with up to 100 and 40 % changes to peripheral artery disease with up to 50 % arterial blockage whereas the change in ankle-brachial index was [Formula: see text]; the same parameters responded with up to 300 and 40 % changes to up to 100 % arterial stiffening while pulse transit time changed by up to 24 %. Together with the development of more convenient techniques for the measurement of arterial blood pressure waveforms, the proposed approach may evolve into a viable alternative to the state-of-the-art techniques for cardiovascular disease diagnosis. PMID- 27655423 TI - Life-course partnership history and midlife health behaviours in a population based birth cohort. AB - BACKGROUND: Marital and partnership history is strongly associated with health in midlife and later life. However, the role of health behaviours as an explanatory mechanism remains unclear. The aim of this study was to investigate prospective associations between life-course partnership trajectories (taking into account timing, non-marital cohabitation, remarriage and marital transitions) and health behaviours measured in midlife. METHODS: We analysed data from the British National Child Development Study, a prospective cohort study that includes all people born in 1 week of March 1958 (N=10 226). This study included men and women with prospective data on partnership history from age 23 to 42-44 and health behaviours collected at ages 42-46 (2000-2004). Latent class analysis was used to derive longitudinal trajectories of partnership history. We used multivariable regression models to estimate the association between midlife health behaviours and partnership trajectory, adjusting for various early and young adult characteristics. RESULTS: After adjustment for a range of potential selection factors in childhood and early adulthood, we found that problem drinking, heavy drinking and smoking were more common in men and women who experienced divorce or who had never married or cohabited. Women who married later had a lower prevalence of smoking and were less likely to be overweight than those who married earlier. Overall marriage was associated with a higher body mass index. Individuals who never married or cohabited spent less time exercising. CONCLUSIONS: Some aspects of partnership history such as remaining unpartnered and experiencing divorce are associated with more smoking and drinking in midlife, whereas marriage is associated with midlife weight gain. Despite these offsetting influences, differences in health behaviours probably account for much of the association between partnership trajectories and health found in previous studies. PMID- 27655424 TI - Value Narratives: A Novel Method for Understanding High-Cost Pediatric Hospital Patients. AB - OBJECTIVES: To delineate the drivers of cost associated with the most-costly inpatients in a tertiary pediatric hospital. METHODS: We identified the 10% most costly inpatients treated at a large regional children's hospital in 2010. From this group we randomly selected, within representative specialties, 2 groups of 50 inpatients for detailed chart review. By using daily cost data and clinical records, 2 independent reviewers examined the clinical course of each patient to identify events that drove cost beyond that expected for standard of care. By using an iterative process, these events were grouped into themes or "cost drivers." Linear regression was used to measure the association of number of cost drivers and total 2010 inpatient cost. RESULTS: We identified 7 cost drivers: medical complications (49%), futile treatment (6%), failure to identify family care preferences (9%), system errors (65%), preventable admissions (21%), complex family dynamics (11%), and expensive diagnosis with no other cost driver (15%). Cost drivers were associated with increased total costs. CONCLUSIONS: We developed a novel method for understanding high-cost inpatients. This method allowed a more detailed understanding of cost drivers than could be achieved with administrative data alone. Many of these cost drivers were related to problems with communication. PMID- 27655425 TI - Growth substrates and caleosin-mediated functions affect conidial virulence in the insect pathogenic fungus Beauveria bassiana. AB - The entomopathogenic fungus, Beauveria bassiana, is a microbial biological control agent capable of infecting a wide range of insect hosts. Conidia (spores) initiate infection via adhesion, growth and penetration of the insect cuticle, whose outmost layer is rich in lipids. Conidial virulence was investigated in B. bassiana WT and caleosin mutants (DeltaBbcal1), the latter a protein involved in lipid storage and turnover. Topical insect bioassays revealed that conidia of the WT strain showed up to 40-fold differences in LD50 values depending upon the growth substrate. The most virulent conidia were harvested from potato dextrose agar containing oleic acid, and the least potent were those derived from Sabouraud dextrose/yeast extract agar (SDAY). However, with the exception of conidia derived from SDAY and Czapek Dox agar, in which values were reduced, mean lethal times to kill (LT50) were essentially unaffected. In topical bioassays, the DeltaBbcal1 mutant displayed LD50 values 5-40-fold higher than the WT depending upon the growth substrate, with DeltaBbcal1 conidia derived from SDAY unable to effectively penetrate the host cuticle. The DeltaBbcal1 mutant also showed concomitant dramatic increases in LT50 values from a mean of ~4.5 for WT to >8.5 days for the mutant. In contrast, intrahaemocoel injection bioassays that bypass cuticle penetration events revealed only minor effects on virulence for either WT or DeltaBbcal1 conidia. These data highlight the importance of caleosin dependent lipid mobilization and/or signalling in cuticle penetration events but suggest their dispensability for immune evasion and within-host growth. PMID- 27655426 TI - The connection between the primary care and the physical activity sector: professionals' perceptions. AB - BACKGROUND: To stimulate physical activity (PA) and guide primary care patients towards local PA facilities, Care Sport Connectors (CSC), to whom a broker role has been ascribed, were introduced in 2012 in the Netherlands. The aim of this study is to assess perceptions of primary care, welfare, and sport professionals towards the CSC role and the connection between the primary care and the PA sector. METHODS: Nine focus groups were held with primary care, welfare and sport professionals within the CSC network. In these focus groups the CSC role and the connection between the sectors were discussed. Both top-down and bottom-up codes were used to analyse the focus groups. RESULTS: Professionals ascribed three roles to the CSC: 1) broker role, 2) referral, 3) facilitator. Professionals were enthusiastic about how the current connection was established. However, barriers relating to their own sector were currently hindering the connection: primary care professionals' lack of time, money and knowledge, and the lack of suitable PA activities and instructors for the target group. CONCLUSIONS: This study provides further insight into the CSC role and the connection between the sectors from the point of view of primary care, welfare, and sport professionals. Professionals found the CSC role promising, but barriers are currently hindering the collaboration between both sectors. More time for the CSC and changes in the way the primary care and PA sector are organized seem to be necessary to overcome the identified barriers and to make a success of the connection. TRIAL REGISTRATION: Dutch Trial register NTR4986 . Registered 14 December 2014. PMID- 27655427 TI - Preclinical evaluation of [(68)Ga]NOTA-pentixafor for PET imaging of CXCR4 expression in vivo - a comparison to [(68)Ga]pentixafor. AB - BACKGROUND: Due to its overexpression in a variety of tumor types, the chemokine receptor 4 (CXCR4) represents a highly relevant diagnostic and therapeutic target in nuclear oncology. Recently, [(68)Ga]pentixafor has emerged as an excellent imaging agent for positron emission tomography (PET) of CXCR4 expression in vivo. In this study, the corresponding [(68)Ga]-1,4,7-triazacyclononane-triacetic acid (NOTA) analog was preclinically evaluated and compared to the 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) parent compound [(68)Ga]pentixafor. METHODS: NOTA-pentixafor was synthesized by combining solid and solution-phase peptide synthesis. The CXCR4 receptor affinities of [(68)Ga]pentixafor and [(68)Ga]NOTA-pentixafor were determined in competitive binding assays using the leukemic CXCR4-expressing Jurkat T-cell line and [(125)I]FC131 as the radioligand. Internalization and cell efflux assays were performed using CXCR4-transfected Chem-1 cells. Small-animal PET and biodistribution studies were carried out using Daudi-tumor bearing SCID mice. RESULTS: [(68)Ga]NOTA-pentixafor showed a 1.4-fold improved affinity towards CXCR4 (IC50). However, internalization efficiency into CXCR4(+)-Chem-1 cells was substantially decreased compared to [(68)Ga]pentixafor. Accordingly, small-animal PET imaging and biodistribution studies revealed a 9.5-fold decreased uptake of [(68)Ga]NOTA-pentixafor in Daudi lymphoma xenografts (1.7 +/- 0.4 % vs 16.2 +/- 3.8 % ID/g at 90 min p.i.) and higher levels of non-specific accumulation, primarily in the excretory organs such as the liver, intestines, and kidneys (2.3 +/- 0.9 % vs 2.0 +/- 0.3 % ID/g, 1.9 +/- 0.8 % vs 0.7 +/- 0.2 % ID/g, and 2.7 +/- 1.1 % vs 1.7 +/- 0.9 % ID/g, respectively). CONCLUSIONS: Despite enhanced CXCR4 affinity in vitro, the [(68)Ga]NOTA-analog of pentixafor showed reduced CXCR4 targeting efficiency in vivo. In combination with enhanced background accumulation, this resulted in significantly inferior PET imaging contrast, and thus, [(68)Ga]NOTA-pentixafor offers no advantages over [(68)Ga]pentixafor. PMID- 27655428 TI - Inter-observer agreement improves with PERCIST 1.0 as opposed to qualitative evaluation in non-small cell lung cancer patients evaluated with F-18-FDG PET/CT early in the course of chemo-radiotherapy. AB - BACKGROUND: The purpose of this study is to determine whether a qualitative approach or a semi-quantitative approach provides the most robust method for early response evaluation with 2'-deoxy-2'-[(18)F]fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body computed tomography (PET/CT) in non-small cell lung cancer (NSCLC). In this study eight Nuclear Medicine consultants analyzed F-18-FDG PET/CT scans from 35 patients with locally advanced NSCLC. Scans were performed at baseline and after 2 cycles of chemotherapy. Each observer used two different methods for evaluation: (1) PET response criteria in solid tumors (PERCIST) 1.0 and (2) a qualitative approach. Both methods allocate patients into one of four response categories (complete and partial metabolic response (CMR and PMR) and stable and progressive metabolic disease (SMD and PMD)). The inter-observer agreement was evaluated using Fleiss' kappa for multiple raters, Cohens kappa for comparison of the two methods, and intraclass correlation coefficients (ICC) for comparison of lean body mass corrected standardized uptake value (SUL) peak measurements. RESULTS: The agreement between observers when determining the percentage change in SULpeak was "almost perfect", with ICC = 0.959. There was a strong agreement among observers allocating patients to the different response categories with a Fleiss kappa of 0.76 (0.71-0.81). In 22 of the 35 patients, complete agreement was observed with PERCIST 1.0. The agreement was lower when using the qualitative method, moderate, having a Fleiss kappa of 0.60 (0.55-0.64). Complete agreement was achieved in only 10 of the 35 patients. The difference between the two methods was statistically significant (p < 0.005) (chi-squared). Comparing the two methods for each individual observer showed Cohen's kappa values ranging from 0.64 to 0.79, translating into a strong agreement between the two methods. CONCLUSIONS: PERCIST 1.0 provides a higher overall agreement between observers than the qualitative approach in categorizing early treatment response in NSCLC patients. The inter-observer agreement is in fact strong when using PERCIST 1.0 even when the level of instruction is purposely kept to a minimum in order to mimic the everyday situation. The variability is largely owing to the subjective elements of the method. PMID- 27655429 TI - Allopurinol reduces the risk of myocardial infarction (MI) in the elderly: a study of Medicare claims. AB - BACKGROUND: Previous observational studies that have examined the association of allopurinol with myocardial infarction (MI) have provided contradictory results. One study showed that allopurinol reduced the risk, while another study showed an increased risk with allopurinol. Therefore, our objective was to assess whether allopurinol use is associated with a reduction in the risk of MI in the elderly. METHOD: We used the 2006-2012 5 % random sample of Medicare beneficiaries to study the association of new allopurinol initiation and the risk of incident MI in a cohort study. Multivariable-adjusted Cox regression models adjusted for age, gender, race, and Charlson index, in addition to various cardio-protective medications (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics, statins). We calculated hazard ratios (HRs) with 95 % confidence intervals (CIs). Sensitivity analyses adjusted for coronary artery disease (CAD) risk factors, including hypertension, hyperlipidemia, diabetes, and smoking. RESULTS: Of the 29,298 episodes of incident allopurinol use, 1544 were associated with incident MI (5.3 % episodes). Allopurinol use was associated with reduced hazards of MI, with a HR of 0.85 (95 % CI, 0.77 to 0.95). Compared to no allopurinol use, longer durations of allopurinol use were associated with a lower HR of MI: 1-180 days, 0.98 (95 % CI, 0.84 to 1.14); 181 days to 2 years, 0.83 (95 % CI, 0.72 to 0.95); and >2 years, 0.70 (95 % CI, 0.56 to 0.88). Other factors associated with a higher hazard of MI were: age 75 to <85 years and >=85 years, male gender, higher Charlson index score, and the use of an ACE inhibitor. Adjustment for CAD risk factors confirmed these findings. CONCLUSION: Incident allopurinol use was associated with a reduction in the risk of incident MI in the elderly. Longer durations of allopurinol use reduced the risk of incident MI incrementally. Future studies should assess the underlying mechanisms for MI prevention and assess the risk-benefit ratio for allopurinol use. PMID- 27655430 TI - Surface characterization and biological properties of regular dentin, demineralized dentin, and deproteinized dentin. AB - Bone autografts are often used for reconstruction of bone defects; however, due to the limitations of autografts, researchers have been in search of bone substitutes. Dentin is of particular interest for this purpose due to high similarity to bone. This in vitro study sought to assess the surface characteristics and biological properties of dentin samples prepared with different treatments. This study was conducted on regular (RD), demineralized (DemD), and deproteinized (DepD) dentin samples. X-ray diffraction and Fourier transform infrared spectroscopy were used for surface characterization. Samples were immersed in simulated body fluid, and their bioactivity was evaluated under a scanning electron microscope. The methyl thiazol tetrazolium assay, scanning electron microscope analysis and quantitative real-time polymerase chain reaction were performed, respectively to assess viability/proliferation, adhesion/morphology and osteoblast differentiation of cultured human dental pulp stem cells on dentin powders. Of the three dentin samples, DepD showed the highest and RD showed the lowest rate of formation and deposition of hydroxyapatite crystals. Although, the difference in superficial apatite was not significant among samples, functional groups on the surface, however, were more distinct on DepD. At four weeks, hydroxyapatite deposits were noted as needle shaped accumulations on DemD sample and numerous hexagonal HA deposit masses were seen, covering the surface of DepD. The methyl thiazol tetrazolium, scanning electron microscope, and quantitative real-time polymerase chain reaction analyses during the 10-day cell culture on dentin powders showed the highest cell adhesion and viability and rapid differentiation in DepD. Based on the parameters evaluated in this in vitro study, DepD showed high rate of formation/deposition of hydroxyapatite crystals and adhesion/viability/osteogenic differentiation of human dental pulp stem cells, which may support its osteoinductive/osteoconductive potential for bone regeneration. PMID- 27655431 TI - Experimental wound dressings of degradable PHA for skin defect repair. AB - The present study reports construction of wound dressing materials from degradable natural polymers such as hydroxy derivatives of carboxylic acids (PHAs) and 3-hydroxybutyrate/4-hydroxybutyrate [P(3HB/4HB)] as copolymer. The developed polymer films and electrospun membranes were evaluated for its wound healing properties with Grafts-elastic nonwoven membranes carrying fibroblast cells derived from adipose tissue multipotent mesenchymal stem cells. The efficacy of nonwoven membranes of P(3HB/4HB) carrying the culture of allogenic fibroblasts was assessed against model skin defects in Wistar rats. The morphological, histological and molecular studies revealed the presence of fibroblasts on dressing materials which facilitated wound healing, vascularization and regeneration. Further it was also observed that cells secreted extracellular matrix proteins which formed a layer on the surface of membranes and promoted the migration of epidermal cells from the neighboring tissues surrounding the wound. The wounds under the P(3HB/4HB) membrane carrying cells healed 1.4 times faster than the wounds under the cell-free membrane and 3.5 times faster than the wounds healing under the eschar (control).The complete wound healing process was achieved at Day 14. Thus the study highlights the importance of nonwoven membranes developed from degradable P(3HB/4HB) polymers in reducing inflammation, enhancing angiogenic properties of skin and facilitating better wound healing process. PMID- 27655432 TI - Clinical and imaging considerations in primary immunodeficiency disorders: an update. AB - Primary immunodeficiencies are a group of genetically determined disorders with diverse presentations. The purpose of this review is to provide a practical and brief description of a select number of these diseases and to discuss the important role the radiologist can have in making an early diagnosis and in detecting and following disease complications. The role of diagnostic imaging and informed performance and interpretation are vital in the diagnosis, surveillance and management of all primary immunodeficiency disorders. PMID- 27655434 TI - PD-1, CTLA-4 Point to Drug Response. AB - In a study of patients with metastatic melanoma, researchers reported that higher numbers of cytotoxic T cells positive for both PD-1 and CTLA-4 in the tumor predicted response to anti-PD-1 therapy and improved progression-free survival. PMID- 27655433 TI - A Recurrent ERCC3 Truncating Mutation Confers Moderate Risk for Breast Cancer. AB - : Known gene mutations account for approximately 50% of the hereditary risk for breast cancer. Moderate and low penetrance variants, discovered by genomic approaches, account for an as-yet-unknown proportion of the remaining heritability. A truncating mutation c.325C>T:p.Arg109* (R109X) in the ATP dependent helicase ERCC3 was observed recurrently among exomes sequenced in BRCA wild-type, breast cancer-affected individuals of Ashkenazi Jewish ancestry. Modeling of the mutation in ERCC3-deficient or CRISPR/Cas9-edited cell lines showed a consistent pattern of reduced expression of the protein and concomitant hypomorphic functionality when challenged with UVC exposure or treatment with the DNA alkylating agent IlludinS. Overexpressing the mutant protein in ERCC3 deficient cells only partially rescued their DNA repair-deficient phenotype. Comparison of frequency of this recurrent mutation in over 6,500 chromosomes of breast cancer cases and 6,800 Ashkenazi controls showed significant association with breast cancer risk (ORBC = 1.53, ORER+ = 1.73), particularly for the estrogen receptor-positive subset (P < 0.007). SIGNIFICANCE: A functionally significant recurrent ERCC3 mutation increased the risk for breast cancer in a genetic isolate. Mutated cell lines showed lower survival after in vitro exposure to DNA-damaging agents. Thus, similar to tumors arising in the background of homologous repair defects, mutations in nucleotide excision repair genes such as ERCC3 could constitute potential therapeutic targets in a subset of hereditary breast cancers. Cancer Discov; 6(11); 1267-75. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 1197. PMID- 27655436 TI - Prevalence and factors associated with the occurrence of bacterial enteropathogens in suckling piglets in farrow-to-finish herds. AB - The aim of the study was to determine both environmental and infectious factors, influencing occurrence of bacterial enteropathogens in suckling piglets. For this purpose, a cross-sectional study in 70 Polish farrow-to-finish pig herds was performed. In each herd, presence of selected intestinal pathogens (Escherichia coli, Clostridium perfringens and Salmonella species) in faeces of suckling piglets were determined using bacteriological and PCR methods. Using logistic regression models, risk factors for enterotoxigenic E coli with fimbriae F4 (ETEC F4) and C perfringens type A were established. Prevalence of bacterial enteropathogens in investigated herds was as follows (on herd and sample level): ETEC-F4 30.0 per cent and 9.3 per cent, respectively, C perfringens type A 91.4 per cent and 58.3 per cent, C perfringens type C 1.4 per cent and 0.3 per cent, Salmonella species 2.9 per cent and 0.5 per cent. The occurrence of ETEC-F4 was associated with presence of diarrhoea in piglets and vulval discharge in sows. Vulval discharge in sows, not slatted floor in farrowing pen and lack of coccidiosis prevention were determined as risk factors for C perfringens type A. The results obtained in the study revealed the high prevalence of enteropathogenic bacteria in pig herds and indicate management and organisation of production as factors having the greatest impact on the incidence of bacterial enteropathogens in piglets before weaning. PMID- 27655437 TI - Frailty and exercise interventions : Evidence and barriers for exercise programs. AB - BACKGROUND: Due to the worldwide demographic transition healthcare systems are facing new demands and are increasingly confronted with an older population with specific medical needs related to multiple chronic disorders. The majority of older persons have an increased risk of frailty. In addition to pharmaceutical interventions another beneficial approach for counteracting frailty might be exercise or physical activity intervention. OBJECTIVE: The first goal was to narratively investigate the state of the art effective exercise interventions for frail older persons and briefly discuss the importance of exercise intervention for frailty. The second goal was to give recommendations to overcome barriers in the recruitment process and how to increase adherence of frail older persons in exercise programs. RESULTS: Several systematic reviews came to the same conclusion that exercise has beneficial effects in frail older persons although uncertainty exists on the optimal exercise program with regard to frequency, type of exercise and duration. Furthermore, all reviews demonstrated the superior nature of multicomponent exercise programs as opposed to single component exercise programs. With regard to barriers different levels have to be taken into account and addressed: older persons themselves with self-efficacy and attitudes, the healthcare personnel involved and the provider of the intervention program. CONCLUSION: Exercise seems a promising approach to counteract frailty but including frail older persons in research programs is challenging. Researchers have to be aware of the different levels of possible barriers ranging from older frail persons and medical personnel to researchers. PMID- 27655435 TI - Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy. AB - : The PI3K pathway is hyperactivated in most cancers, yet the capacity of PI3K inhibitors to induce tumor cell death is limited. The efficacy of PI3K inhibition can also derive from interference with the cancer cells' ability to respond to stromal signals, as illustrated by the approved PI3Kdelta inhibitor idelalisib in B-cell malignancies. Inhibition of the leukocyte-enriched PI3Kdelta or PI3Kgamma may unleash antitumor T-cell responses by inhibiting regulatory T cells and immune-suppressive myeloid cells. Moreover, tumor angiogenesis may be targeted by PI3K inhibitors to enhance cancer therapy. Future work should therefore also explore the effects of PI3K inhibitors on the tumor stroma, in addition to their cancer cell-intrinsic impact. SIGNIFICANCE: The PI3K pathway extends beyond the direct regulation of cancer cell proliferation and survival. In B-cell malignancies, targeting PI3K purges the tumor cells from their protective microenvironment. Moreover, we propose that PI3K isoform-selective inhibitors may be exploited in the context of cancer immunotherapy and by targeting angiogenesis to improve drug and immune cell delivery. Cancer Discov; 6(10); 1090-105. (c)2016 AACR. PMID- 27655438 TI - Estimation of the dietary requirement for vitamin D in adolescents aged 14-18 y: a dose-response, double-blind, randomized placebo-controlled trial. AB - BACKGROUND: Adolescents are a population group at high risk of low vitamin D status, yet the evidence base for establishing dietary vitamin D requirements remains weak. OBJECTIVE: The aim was to establish the distribution of vitamin D intakes required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above proposed cutoffs (25, 30, 40, and 50 nmol/L) during winter in white males and females (14-18 y of age) in the United Kingdom (51 degrees N). DESIGN: In a dose-response trial, 110 adolescents (aged 15.9 +/- 1.4 y; 43% males) were randomly assigned to receive 0, 10, or 20 MUg vitamin D3 supplements/d for 20 wk during winter. A nonlinear regression model was fit to total vitamin D intake and postintervention serum 25(OH)D concentrations, and regression-predicted values estimated the vitamin D intakes required to maintain serum 25(OH)D concentrations above specific cutoffs. RESULTS: Mean +/- SD serum 25(OH)D concentrations increased from 49.2 +/- 12.0 to 56.6 +/- 12.4 nmol/L and from 51.7 +/- 13.4 to 63.9 +/- 10.6 nmol/L in the 10- and 20-MUg/d groups, respectively, and decreased in the placebo group from 46.8 +/- 11.4 to 30.7 +/- 8.6 nmol/L (all P <= 0.001). Vitamin D intakes required to maintain 25(OH)D concentrations >25 and >30 nmol/L in 97.5% of adolescents were estimated to be 10.1 and 13.1 MUg/d, respectively, and 6.6 MUg/d to maintain 50% of adolescents at concentrations >40 nmol/L. Because the response of 25(OH)D reached a plateau at 46 nmol/L, there is uncertainty in estimating the vitamin D intake required to maintain 25(OH)D concentrations >50 nmol/L in 97.5% of adolescents, but it exceeded 30 MUg/d. CONCLUSION: Vitamin D intakes between 10 and ~30 MUg/d are required by white adolescents during winter to maintain serum 25(OH)D concentrations >25-50 nmol/L, depending on the serum 25(OH)D threshold chosen. This trial was registered at clinicaltrials.gov as NCT02150122 and as International Standard Randomized Controlled Trial Number ISRCTN40736890. PMID- 27655440 TI - Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers. AB - BACKGROUND: The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men. OBJECTIVE: We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed macronutrient drink and subsequent energy intake. DESIGN: In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying (13C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed. RESULTS: Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P < 0.05) and tended to reduce peak blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P < 0.01 for both), but neither dose affected glucagon, GLP-1, GIP, cholecystokinin, gastric emptying, or energy intake. Compared with the control, isoleucine-10g reduced the blood glucose AUC and peak blood glucose (P < 0.01), whereas effects of isoleucine-5g were NS. Neither load affected insulin, C-peptide, glucagon, GLP-1, or GIP. Isoleucine-10g, but not isoleucine-5g, slowed gastric emptying (P < 0.05), but gastric emptying was not correlated with the blood glucose AUC. Isoleucine did not affect energy intake. CONCLUSIONS: In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628. PMID- 27655439 TI - Dietary flavonoid intake and incident coronary heart disease: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. AB - BACKGROUND: Flavonoids are dietary polyphenolic compounds with a variety of proposed beneficial cardiovascular effects, but rigorous prospective studies that examine the association between flavonoid intake and incident coronary heart disease (CHD) in geographically and racially diverse US samples are limited. OBJECTIVE: With the use of the new, expanded USDA flavonoid database, we assessed the association between total flavonoid and flavonoid subclass intakes with incident CHD in a biracial and geographically diverse cohort, as well as effect modification by age, sex, race, and region of residence. DESIGN: Participants were 16,678 black and white men and women enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a national prospective cohort study. All participants were without CHD at baseline, and all completed a Block98 food-frequency questionnaire. Flavonoid intakes were estimated from USDA flavonoid databases, which were recently improved to address missing values for cooked foods and to adjust for flavonoid losses due to processing. Incident CHD events were participant reported and adjudicated by experts. Quintiles of flavonoid intake were examined as predictors of incident CHD by using Cox proportional hazards regression to obtain HRs. Tests for trend used the quintile medians. RESULTS: Over a mean +/- SD follow-up of 6.0 +/- 1.9 y, 589 CHD events occurred. High flavonoid intake was associated with self-identified white race, exercise, not smoking, more education, and higher income. In models that adjusted for sociodemographic, health behavior, and dietary factors, there was an inverse association between anthocyanidin and proanthocyanidin intakes and incident CHD (HRs for quintile 5 compared with quintile 1-anthocyanidins: 0.71; 95% CI: 0.52, 0.98; P-trend = 0.04; proanthocyanidins: 0.63; 95% CI: 0.47, 0.84; P-trend = 0.02). There was no association between total flavonoid or other flavonoid subclass intakes and incident CHD. CONCLUSIONS: Reported anthocyanidin and proanthocyanidin intakes were inversely associated with incident CHD. There was no significant effect modification by age, sex, race, or region of residence. PMID- 27655443 TI - Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model. AB - BACKGROUND: Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. OBJECTIVE: In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. DESIGN: Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. RESULTS: Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. CONCLUSION: The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus provides essential information for the development of optimal LNAA supplementation as an alternative dietary treatment strategy to optimize neurocognitive outcome in patients with phenylketonuria. PMID- 27655441 TI - Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study. AB - BACKGROUND: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. OBJECTIVE: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM. DESIGN: Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6-59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling. RESULTS: Fatal subjects (n = 14; 18%) were younger (mean +/- SD age: 17 +/- 11 compared with 25 +/- 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443-535 mg/kg feces) compared with 698 mg/kg feces (1438-244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112-22 ng/mL) compared with 2036 ng/mL (5800-149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831-131 ng/mL) compared with 3174 ng/mL (5819-357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation. CONCLUSIONS: Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of inflammatory changes in SAM, which may lead to improved therapies. This trial was registered at www.controlled-trials.com as ISRCTN13916953. PMID- 27655442 TI - Prospective associations of maternal betaine status with offspring weight and body composition at birth: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study. AB - BACKGROUND: Betaine supplementation results in lower body weight and fat mass and higher lean mass in animals and adult humans. However, the relation between maternal betaine status and offspring birth weight and body composition is less known. OBJECTIVE: The aim was to examine the association between maternal betaine status and neonatal birth size and adiposity in an Asian mother-offspring cohort. DESIGN: We included 955 pregnant women whose plasma betaine concentrations were measured at 26-28 wk of gestation. Neonatal anthropometric values were measured at birth, and abdominal adipose tissue compartments were assessed by MRI in a subset of infants (n = 307) in the first 14 d after birth. Multivariate general linear models were used to adjust for gestational age; fetal sex; and maternal age, height, education, ethnicity, prepregnancy body mass index, and plasma folate, vitamin B-12, and choline concentrations. RESULTS: The mean +/- SD plasma concentration of betaine was 13.2 +/- 2.7 MUmol/L (range: 5.3-25.0 MUmol/L). After adjustment for covariates, higher maternal plasma betaine was associated with lower birth weight (beta: -57.6 g; 95% CI: -109.9, -5.3 g), shorter birth length (beta: -0.29 cm per 5-MUmol/L increment; 95% CI: -0.55, -0.03 cm), smaller head circumference (-0.20 cm; 95% CI: -0.38, -0.02 cm), smaller midupper arm circumference (-0.16 cm; 95% CI: -0.30, -0.03 cm), lower volumes of abdominal superficial subcutaneous adipose tissue (-4.53 mL; 95% CI: -8.70, -0.36 mL), and a higher risk of small-for-gestational-age birth (OR: 1.57; 95% CI: 1.05, 2.35). CONCLUSIONS: Higher maternal betaine status was generally associated with smaller infant birth size and less abdominal fat mass. Further studies are needed to replicate these findings and to understand their biological mechanisms. This study was registered at clinicaltrials.gov as NCT01174875. PMID- 27655444 TI - Treadmill Exercise Improves Fracture Toughness and Indentation Modulus without Altering the Nanoscale Morphology of Collagen in Mice. AB - The specifics of how the nanoscale properties of collagen (e.g., the crosslinking profile) affect the mechanical integrity of bone at larger length scales is poorly understood despite growing evidence that collagen's nanoscale properties are altered with disease. Additionally, mass independent increases in postyield displacement due to exercise suggest loading-induced improvements in bone quality associated with collagen. To test whether disease-induced reductions in bone quality driven by alterations in collagen can be rescued or prevented via exercise-mediated changes to collagen's nanoscale morphology and mechanical properties, the effects of treadmill exercise and beta-aminopropionitrile treatment were investigated. Eight week old female C57BL/6 mice were given a daily subcutaneous injection of either 164 mg/kg beta-aminopropionitrile or phosphate buffered saline while experiencing either normal cage activity or 30 min of treadmill exercise for 21 consecutive days. Despite differences in D spacing distribution (P = 0.003) and increased cortical area (tibial: P = 0.005 and femoral: P = 0.015) due to beta-aminopropionitrile treatment, an overt mechanical disease state was not achieved as there were no differences in fracture toughness or 4 point bending due to beta-aminopropionitrile treatment. While exercise did not alter (P = 0.058) the D-spacing distribution of collagen or prevent (P < 0.001) the beta-aminopropionitrile-induced changes present in the unexercised animals, there were differential effects in the distribution of the reduced elastic modulus due to exercise between control and beta aminopropionitrile-treated animals (P < 0.001). Fracture toughness was increased (P = 0.043) as a main effect of exercise, but no significant differences due to exercise were observed using 4 point bending. Future studies should examine the potential for sex specific differences in the dose of beta-aminopropionitrile required to induce mechanical effects in mice and the contributions of other nanoscale aspects of bone (e.g., the mineral-collagen interface) to elucidate the mechanism for the exercise-based improvements in fracture toughness observed here and the increased postyield deformation observed in other studies. PMID- 27655447 TI - Quasi-periodic fluctuation in Donchin's speller signals and its potential use for asynchronous control. AB - When we examine the event-related potential (ERP) responses of Donchin's brain computer interface (BCI) speller, a type of quasi-periodic fluctuation (FLUC) overlapping with the ERP components can be observed; this fluctuation is traditionally treated as interference. However, if the FLUC is detectable in a working BCI, it can be used for asynchronous control, i.e. to indicate whether the BCI is under the control state (CS) or under the non-control idle state (NC). Asynchronous control is an important issue to address to enable BCI's practical use. In this paper, we examine the characteristics of the FLUC and explore the possibility of using the FLUC for asynchronous control of the BCI. For detecting the FLUC, we propose a method based on the power spectrum and evaluate the detection rates in a simulation. As a result, high true positive rates (TPRs) and low false positive rates (FPRs) are obtained. Our work reveals that the FLUC is of great value for implementing an asynchronous BCI. PMID- 27655445 TI - Disruption of the Hedgehog signaling pathway in inflammatory bowel disease fosters chronic intestinal inflammation. AB - Hedgehog (Hh) signaling is essential for intestinal homeostasis and has been associated with inflammation and tissue repair. We hypothesized that Hh signaling could affect the inflammatory process in inflammatory bowel disease (IBD). For this purpose, colon specimens from the inflamed and non-inflamed mucosa of 15 patients with Crohn's disease (CD), 15 with ulcerative colitis, and 15 controls were analyzed by immunohistochemistry and real-time PCR. The production and modulation of cytokines were measured by ELISA from culture explants. Apoptosis was assessed by TUNEL and caspase-3 activity assays. Chemotaxis was evaluated using a transwell system. Primary human intestinal and skin fibroblasts were used for analyzing migration and BrdU incorporation. Hh proteins were generally expressed at the superficial epithelium, and a marked reduction was observed in CD. In the lamina propria, Gli-1 predominantly co-localized with vimentin- and alpha-smooth muscle actin-positive cells, with lower levels observed in CD. In colon explants, Hh stimulation resulted in reduction, while blockade increased, TNF alpha, IL-17, and TGF beta levels. Apoptotic rates were higher in inflamed samples, and they increased after Hh blockade. Levels of Gli-1 mRNA were negatively correlated with caspase-3 activity. Hh blockade increased chemoattraction of monocytes. Primary fibroblasts incorporated more BrdU, but migrated less after Hh blockade. These results suggest that Hh signaling provides a negative feedback to the lamina propria, down-regulating inflammatory cytokines, and inhibiting leukocyte migration and fibroblast proliferation, while favoring fibroblast migration. Therefore, Hh signaling is strongly implicated in the pathogenesis of intestinal inflammation, and it may represent a novel therapeutic target for IBD. PMID- 27655448 TI - A simulation framework for correlated count data of features subsets in high throughput sequencing or proteomics experiments. AB - As part of the data processing of high-throughput-sequencing experiments count data are produced representing the amount of reads that map to specific genomic regions. Count data also arise in mass spectrometric experiments for the detection of protein-protein interactions. For evaluating new computational methods for the analysis of sequencing count data or spectral count data from proteomics experiments artificial count data is thus required. Although, some methods for the generation of artificial sequencing count data have been proposed, all of them simulate single sequencing runs, omitting thus the correlation structure between the individual genomic features, or they are limited to specific structures. We propose to draw correlated data from the multivariate normal distribution and round these continuous data in order to obtain discrete counts. In our approach, the required distribution parameters can either be constructed in different ways or estimated from real count data. Because rounding affects the correlation structure we evaluate the use of shrinkage estimators that have already been used in the context of artificial expression data from DNA microarrays. Our approach turned out to be useful for the simulation of counts for defined subsets of features such as individual pathways or GO categories. PMID- 27655446 TI - Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings. AB - Hepatic stellate cells (HSCs), also known as perisinusoidal cells, are pericytes found in the perisinusoidal space of the liver. HSCs are the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage. When the liver is damaged, stellate cells can shift into an activated state, characterized by proliferation, contractility and chemotaxis. The activated HSCs secrete collagen scar tissue, which can lead to cirrhosis. Recent studies have shown that in vivo activation of HSCs by fibrogenic agents can eventually lead to senescence of these cells, which would contribute to reversal of fibrosis although it may also favor the insurgence of liver cancer. HSCs in their non-active form store huge amounts of retinoic acid derivatives in lipid droplets, which are progressively depleted upon cell activation in injured liver. Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A, generally required for growth and development. The precise function of retinoic acid and its alterations in HSCs has yet to be elucidated, and nonetheless in various cell types retinoic acid and its receptors (RAR and RXR) are known to act synergistically with peroxisome proliferator activated receptor gamma (PPAR-gamma) signaling through the activity of transcriptional heterodimers. Here, we review the recent advancements in the understanding of how retinoic acid signaling modulates the fibrogenic potential of HSCs and proposes a synergistic combined action with PPAR-gamma in the reversal of liver fibrosis. PMID- 27655449 TI - Increased Mortality in Relation to Insomnia and Obstructive Sleep Apnea in Korean Patients Studied with Nocturnal Polysomnography. AB - STUDY OBJECTIVES: To elucidate the links between the two most prevalent sleep disorders, insomnia and obstructive sleep apnea (OSA), and mortality. METHODS: We studied 4,225 subjects who were referred to the Center for Sleep and Chronobiology, Seoul National University Hospital, from January 1994 to December 2008. We divided the subjects into five groups: mild OSA (5 <= AHI < 15), moderate OSA (15 <= AHI < 30), severe OSA (AHI >= 30), insomnia, and a no-sleep disorder group consisting of subjects without sleep disorders. Standardized mortality ratio (SMR), hazard ratio, and the survival rates of the five groups were calculated and evaluated. RESULTS: The SMR of all-cause mortality was significantly higher in the severe OSA group than in the general population (1.52, 95% CI 1.23-1.85, p < 0.05). The SMR of cardiovascular mortality increased progressively with the severity of OSA (no-sleep-disorder: 0.09, mild: 0.40, moderate: 0.52, severe: 1.79, p < 0.05). Statistical analyses of the hazard ratios indicated that severe OSA is a risk factor for all-cause mortality (HR 3.50, 95% CI 1.03-11.91, p = 0.045) and cardiovascular mortality (HR 17.16, 95% CI 2.29-128.83, p = 0.006). Cardiovascular mortality was also significantly elevated in the insomnia group (HR 8.11, 95% CI 1.03-63.58, p = 0.046). CONCLUSIONS: Severe OSA was associated with increased all-cause mortality and cardiovascular mortality compared to the no-sleep-disorder group. Insomnia was associated with increased cardiovascular mortality compared to the no-sleep disorder group. PMID- 27655450 TI - Depth and Distribution of Symptoms in Restless Legs Syndrome/ Willis-Ekbom Disease. AB - STUDY OBJECTIVES: To determine the depth and distribution of sensory discomfort in idiopathic restless legs syndrome/Willis-Ekbom disease (RLS) and RLS concurrent with other leg conditions, specifically peripheral neuropathy, sciatica, leg cramps, and arthritis. METHODS: RLS subjects (n = 122) were divided into 71 idiopathic RLS and 51 RLS-C, or Comorbid, groups. All subjects were examined by an RLS expert, answered standardized RLS questionnaires, and received a body diagram to draw the location and depth of their symptoms. RESULTS: Age was 63.04 +/- 12.84 years, with 77 females and 45 males. All patients had lower limb involvement and 43/122 (35.25%) also had upper limb involvement. Of the 122 subjects, 42.62% felt that the RLS discomfort was only deep, 9.84% felt that the discomfort was only superficial, and 47.54% felt both superficial and deep discomfort. There were no defining characteristics in depth or distribution of RLS sensations that differentiated those patients with idiopathic RLS from those patients with RLS associated with other comorbid leg conditions. The sensation of arthritis was felt almost exclusively in the joints and not in the four quadrants of the leg, whereas the exact opposite was true of RLS sensations. CONCLUSIONS: Depth and distribution cannot be used as a discriminative mechanism to separate out idiopathic RLS from RLS comorbid with other leg conditions. Although seen in clinical practice, the total absence of patients with non-painful RLS only in the joints in the current study attests to the rarity of this presentation and raises the possibility of misdiagnosis under these circumstances. We recommend that such patients not be admitted to genetic or epidemiological studies. PMID- 27655451 TI - Importance of Urinary Drug Screening in the Multiple Sleep Latency Test and Maintenance of Wakefulness Test. AB - STUDY OBJECTIVES: Multiple sleep latency testing (MSLT) and the maintenance of wakefulness test (MWT) are gold-standard objective tests of daytime sleepiness and alertness; however, there is marked variability in their interpretation and practice. This study aimed to determine the incidence of positive drug screens and their influence on MSLT, MWT, and polysomnographic variables. METHODS: All patients attending Eastern Health Sleep Laboratory for MSLT or MWT over a 21-mo period were included in the study. Urinary drug screening for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates was performed following overnight polysomnography (PSG). Demographics and PSG variables were compared. RESULTS: Of 69 studies, MSLT (43) and MWT (26), 16% of patients had positive urinary drug screening (7 MSLT; 4 MWT). Drugs detected included amphetamines, cannabinoids, opiates, and benzodiazepines. No patient self-reported use of these medications prior to testing. No demographic, MSLT or MWT PSG data or overnight PSG data showed any statistical differences between positive and negative drug screen groups. Of seven MSLT patients testing positive for drug use, one met criteria for the diagnosis of narcolepsy and five for idiopathic hypersomnia. On MWT, three of the four drug-positive patients had a history of a motor vehicle accident and two patients were occupational drivers. CONCLUSIONS: These findings indicate drug use is present in patients attending for daytime testing of objective sleepiness and wakefulness. These data support routine urinary drug screening in all patients undergoing MSLT or MWT studies to ensure accurate interpretation in the context of illicit and prescription drug use. PMID- 27655452 TI - Revisions to the Behavioral Risk Factor Surveillance System Sleep Questions. AB - STUDY OBJECTIVES: To revise and enhance the current Behavioral Risk Factor Surveillance System (BRFSS) sleep questions for detection of sleep/wake disorders that contribute to health burden. METHODS: A descriptive qualitative design was used to guide the investigation. The three methods were (1) a review of the current evidence on sleep related screening questions (including the results from the parent study validating the current BRFSS questions), (2) interviews with sleep experts about the questions they use in their clinical practice to screen for sleep problems, and (3) interviews with lay people to discuss contextual meanings, feelings, and beliefs about sufficient and restful sleep and not feeling rested. RESULTS: Recommendations for revisions of the current BRFSS questions. CONCLUSIONS: The current BRFSS questions should be refined to better screen for sleep disorders. PMID- 27655453 TI - Cerebral Microbleeds on MRI in Patients with Obstructive Sleep Apnea. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is known to increase the risk of stroke. Cerebral microbleeds (CMBs) are considered one of the precursors to symptomatic stroke. We aimed to clarify the relationship between OSA and CMBs. METHODS: We recruited patients who visited our clinic for the evaluation of sleep disordered breathing. All patients underwent both overnight polysomnography and brain magnetic resonance imaging, which included T2*-weighted gradient-recalled echo images. We applied multivariate logistic regression and partial correlation analysis to estimate the relationship between OSA and CMBs. RESULTS: A total of 75 (45 male, 30 female) patients were enrolled. Their mean age was 60.5 years. Patients with CMBs had a significantly higher apneahypopnea index (AHI) compared with those without CMBs. AHI equal to or greater than 15 was a significant independent predictor of CMBs (adjusted odds ratio, 4.51; 95% CI, 1.40-14.58; p = 0.012) in the multivariate regression analysis. In addition, a partial correlation analysis adjusted for age, hypertension, diabetes, and cardiovascular disease revealed a positive relationship between AHI and the number of CMBs (r = 0.585, p = 0.028). CONCLUSIONS: Moderate-to-severe OSA can be one of the independent predictors of CMBs which are considered a surrogate marker of overt stroke. PMID- 27655456 TI - Severe Postictal Hypoxemia-Associated Seizure in a 12-Year-Old Child. AB - ABSTRACT: A 9 year-old girl with developmental delay and seizure disorder presented for evaluation of witnessed breathing pauses during sleep that were not associated with snoring or gasping. Polysomnography showed a generalized seizure with post ictal central apnea associated with severe desaturation and a post central apnea brief seizure. This case report discusses the pathophysiology of post-ictal desaturations and breathing abnormalities during seizures and their possible association with sudden unexpected death in epilepsy. The case also demonstrates the utility of polysomnography for the diagnosis of breathing abnormalities associated with seizures. PMID- 27655455 TI - Obstructive Sleep Apnea without Obesity Is Common and Difficult to Treat: Evidence for a Distinct Pathophysiological Phenotype. AB - STUDY OBJECTIVES: To determine the proportion and physiological characteristics of nonobese patients with obstructive sleep apnea (OSA) and their response to prescribed therapy. METHODS: Data from 163 consecutive in-laboratory diagnostic sleep studies for participants referred to an academic teaching-hospital sleep clinic for suspected OSA were assessed. Sleep and anthropometric parameters at baseline and follow-up (up to 22 mo) were examined and compared between obese and nonobese patients with a diagnosis of OSA (apnea-hypopnea index > 5 events/h sleep). A key nonanatomical contributor to OSA pathogenesis, the respiratory arousal threshold, was compared between groups. RESULTS: Twenty-five percent of the participants with a diagnosis of OSA had a body mass index (BMI) within the normal range (BMI < 25 kg/m2) and 54% had a BMI < 30 kg/m2 (nonobese). Of the patients prescribed continuous positive airway pressure (CPAP), more nonobese patients reported not using their CPAP machine at all at follow-up (36% vs. 13%, p = 0.03). Objective CPAP compliance was also lower in the nonobese patients with OSA (5.1 +/- 0.4 vs. 6.4 +/- 0.4 h/night, p < 0.03). A higher proportion of the nonobese patients had a low respiratory arousal threshold compared to obese OSA patients (86% vs. 60%, p < 0.001). CONCLUSIONS: A substantial proportion of patients with OSA are not obese. These patients are challenging to treat with existing therapies as they are less adherent and compliant with CPAP therapy. Nonanatomical contributors to OSA, such a low threshold for arousal, are likely to be particularly important in OSA pathogenesis in nonobese patients with OSA. These findings have important implications for the pathogenesis of OSA in nonobese patients and potential therapeutic targets for this group of patients. PMID- 27655454 TI - Unanticipated Nocturnal Oxygen Requirement during Positive Pressure Therapy for Sleep Apnea and Medical Comorbidities. AB - STUDY OBJECTIVES: Home-based management of sleep-disordered breathing (SDB) generally excludes patients with significant medical comorbidities, but such an approach lacks scientific evidence. The current study examined whether significant medical comorbidities are associated with persistent hypoxia that requires unanticipated nocturnal O2 supplementation to positive airway pressure (PAP) therapy. Conceivably, in such patients, home-based management of SDB may not detect or therefore adequately treat persistent hypoxia. METHODS: In this retrospective study of 200 patients undergoing laboratory-based polysomnography, we ascertained significant medical comorbidities (chronic obstructive pulmonary disease, congestive heart failure, and morbid obesity) and their association with the need for unanticipated O2 supplementation to PAP therapy. Postural oxygen (SpO2) desaturations between upright and reclining positions were determined during calm wakefulness. RESULTS: Postural change in SpO2 during calm wakefulness was greater in patients who eventually needed nocturnal O2 supplementation to PAP therapy than those needing PAP therapy alone (p < 0.0001). The presence of chronic obstructive pulmonary disease (odds ratio [OR] 6.0; 95% confidence interval [CI]; 2.1, 17.5; p = 0.001), morbid obesity (OR 3.6; 95% CI 1.9, 7.0; p < 0.0001), and age older than 50 y (OR 2.8; 95% CI 1.3, 5.9; p = 0.007) but not heart failure were associated with unanticipated need for nocturnal O2 supplementation. A clinical prediction rule of less than two determinants (age older than 50 y, morbid obesity, chronic obstructive pulmonary disease, and postural SpO2 desaturation greater than 5%) had excellent negative predictive value (0.92; 95% CI 0.85, 0.96) and likelihood ratio of negative test (0.08; 95% CI 0.04, 0.16). CONCLUSIONS: Medical comorbidities can predict persistent hypoxia that requires unanticipated O2 supplementation to PAP therapy. Such findings justify the use of medical comorbidities to exclude home management of SDB. COMMENTARY: A commentary on this article appears in this issue on page 7. PMID- 27655458 TI - Case Study: Imaging of Apnea Termination in a Patient with Obstructive Sleep Apnea during Natural Sleep. AB - ABSTRACT: A 55-year-old woman who presented to the sleep clinic with severe sleep apnea (OSA) (apnea-hypopnea index [AHI] 62) and excessive somnolence (Epworth Sleepiness Scale score 18/24), was imaged with MRI using the Spatial Modulation of Magnetization tagging sequence awake and asleep to visualize upper airway tissue movement. Awake quiet breathing resulted in minimal movement of upper airway tissues. Asleep sequences taken during airway opening post-apnea demonstrated neck extension, mandibular advancement, and widespread tongue deformation accompanying contraction of genioglossus. At the end of the asleep image sequence, the nasopharyngeal airway had a cross-sectional area larger than during quiet breathing awake and there was antero-lateral movement in the lateral walls. In conclusion, the airway responds to apnea by widespread contraction of the genioglossus, followed by mandibular advancement and neck extension. All these maneuvers stabilize and open the airway. PMID- 27655457 TI - Discussion of Extinction-Based Behavioral Sleep Interventions for Young Children and Reasons Why Parents May Find Them Difficult. AB - ABSTRACT: The majority of behavioral sleep interventions for young children involve extinction procedures where parents must ignore their child's cries for a period. Many parents have difficulties with this, contributing to attrition, non compliance, and treatment avoidance. Yet why these methods are difficult to implement has rarely been addressed in the literature. This paper discusses seven potential reasons why parents may find extinction sleep interventions difficult: enduring crying, practical considerations, fear of repercussions, misinformation, incongruence with personal beliefs, different cultural practices, and parent wellness. These reasons are discussed in relation to the current literature. Practicing health professionals and sleep researchers could benefit from an awareness of these issues when suggesting extinction interventions and offering alternatives which may be more appropriate for family circumstances and facilitate parental informed choice. PMID- 27655461 TI - In Memoriam: Thomas E. Meade DDS, 1941-2016. PMID- 27655460 TI - An 18-Year-Old Woman with Prolonged Eyes Closed Unresponsiveness during Multiple Sleep Latency Testing. PMID- 27655459 TI - Sleep Well!: A Pilot Study of an Education Campaign to Improve Sleep of Socioeconomically Disadvantaged Children. AB - STUDY OBJECTIVES: Socioeconomically disadvantaged children are at risk for poor sleep hygiene and increased sleep problems. This pilot study examined the efficacy of Sleep Well!, a parent-based sleep education endeavor, which supplemented an outreach program that provides beds to socioeconomically disadvantaged children. METHODS: In addition to receiving a bed, 152 children (mean age = 5.95 years, 57.2% boys) were randomly assigned to sleep education (3 messages: bedtime before 21:00; no caffeine; keep electronics out of the bedroom) or control (dental hygiene education) conditions. All education was provided at both the time of scheduling and delivery of a bed to each child. Parent-reported sleep data were collected at baseline and at 4-week follow-up. RESULTS: Provision of a bed was associated with reduced bedroom electronics and increased parent reported nighttime sleep duration for all children. However, relative to control children, intervention children showed even greater reductions in electronics (baseline mean = 1.91 items, follow-up mean = 0.85 items) and improvements in sleep duration (baseline mean = 9.75 hours, follow-up mean = 10.19 hours). There was no intervention effect for caffeine consumption or bedtime from baseline to follow-up. CONCLUSIONS: Providing beds to socioeconomically disadvantaged children resulted in increased sleep duration and decreased use of electronics at bedtime, while the combination of a bed and brief parent sleep education conferred additional sleep benefits. Further study of brief child sleep interventions is warranted, particularly among socioeconomically disadvantaged children who are at risk for sleep problems. PMID- 27655462 TI - What's Old is New Again: Fresh Hope for Treatment Refractory Hypersomnolence Patients. PMID- 27655463 TI - Does Subjective Sleep Affect Bone Mineral Density in Older People with Minimal Health Disorders? The PROOF Cohort. AB - STUDY OBJECTIVES: Clinical and epidemiological studies suggest a relation between bone mineral density (BMD) and self-assessment of sleep with an effect on bone formation and osteoporosis (OS) risk in short and long sleepers. This study explores this association in a large sample of older subjects. METHODS: We examined 500 participants without insomnia complaints aged 65.7 +/- 0.8 y. Each participant had a full evaluation including anthropometric measurement, clinical examination and measurements of BMD at the lumbar spine and femoral sites by dual energy X-ray absorptiometry. The daily energy expenditure (DEE) was measured by the Population Physical Activity Questionnaire. Sleep duration and quality were evaluated by the Pittsburgh Sleep Quality Index. The subjects were stratified into three groups according to sleep duration, i.e., short (< 6 h), normal (6-8 h), and long (>= 8 h) sleepers. RESULTS: Osteopenia was found in 40% of the subjects at the femoral level and 43% at the vertebral level. The prevalence of OS was lower both at femoral (8%) and vertebral (12%) levels. Short, normal, and long sleepers accounted for 29%, 40%, and 31% of subjects, respectively. After adjustments for metabolic, anthropometric, and DEE, multinomial logistic regression analysis indicated that long sleepers were more likely to have femoral neck OS with a slight effect of DEE at vertebral spine. CONCLUSIONS: In a sample of older subjects, self-reported long sleep was the best predictor of OS risk at the femoral level. This finding suggests an association between OS and self reported sleep duration in older subjects. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584. PMID- 27655464 TI - Associations of Parent Health Behaviors and Parenting Practices with Sleep Duration in Overweight and Obese Children. AB - STUDY OBJECTIVES: To examine the extent to which parent health behaviors and parenting practices are associated with school-age children's sleep duration. METHODS: We surveyed 790 parents of children, aged 6 to 12 y, who had a body mass index (BMI) >= 90th percentile and were participating in a randomized controlled obesity trial. The main exposures were parent sleep duration, screen time and physical activity, parental limits placed on child TV viewing time and TV content, and parents' confidence regarding their ability to help their child get enough sleep. The primary outcome was child sleep duration. We used linear regression models to examine associations of parent behaviors and parenting practices with child sleep duration. RESULTS: On average, children slept 9.2 h per night, whereas parents slept 6.9 h. Parents reported having an average of 1.9 h of screen time per day and 0.6 h of physical activity. There were 57.3% of parents who reported feeling very/extremely confident that they could help their child get enough sleep. In adjusted multivariate analyses, child sleep duration was 0.09 h/day (95% confidence interval: 0.03, 0.15) longer for each 1-h increment in parent sleep duration. Additionally, children whose parents reported being very/extremely confident they could help their child get age-appropriate sleep duration slept 0.67 h/day longer (95% confidence interval: 0.54, 0.81) than those whose parents were not/somewhat confident. CONCLUSIONS: Educating parents about their own sleep health and enhancing parent confidence to help their children get enough sleep are potential areas of intervention to increase child sleep duration. PMID- 27655465 TI - A Nationwide Cross-Sectional Survey of Sleep-Related Problems in Japanese Visually Impaired Patients: Prevalence and Association with Health-Related Quality of Life. AB - STUDY OBJECTIVES: This questionnaire-based cross-sectional study was conducted (1) to estimate the prevalence of sleep-related problems, and (2) to explore factors associated with lower physical/mental quality of life (QOL), particularly addressing sleep-related problems among Japanese visually impaired people. METHODS: This nationwide questionnaire-based survey was administered to visually impaired individuals through the Japan Federation of the Blind. Visually impaired individuals without light perception (LP) (n = 311), those with LP (n = 287), and age-matched and gender-matched controls (n = 615) were eligible for this study. Study questionnaires elicited demographic information, and information about visual impairment status, sleep-related problems, and health-related quality of life. RESULTS: Visually impaired individuals with and without LP showed higher prevalence rates of irregular sleep-wake patterns and difficulty maintaining sleep than controls (34.7% and 29.4% vs. 15.8%, 60.1% and 46.7% vs. 26.8%, respectively; p < 0.001). These sleep-related problems were observed more frequently in visually impaired individuals without LP than in those with LP. Non restorative sleep or excessive daytime sleepiness was associated with lower mental/physical QOL in visually impaired individuals with LP and in control subjects. However, visually impaired individuals without LP showed irregular sleep-wake pattern or difficulty waking up at the desired time, which was associated with lower mental/physical QOL. CONCLUSIONS: Sleep-related problems were observed more frequently in visually impaired individuals than in controls. Moreover, the rates of difficulties were higher among subjects without LP. Sleep related problems, especially circadian rhythm-related ones, can be associated with lower mental/physical QOL in visually impaired individuals without LP. PMID- 27655466 TI - Validation of a Suprasternal Pressure Sensor for Sleep Apnea Classification in Children. AB - STUDY OBJECTIVES: The recognition and characterization of respiratory events is crucial when interpreting sleep studies. The aim of the study was to validate the PneaVoX sensor, which integrates the recording of respiratory effort by means of suprasternal pressure (SSP), respiratory flow, and snoring for the classification of sleep apneas in children. METHODS: Sleep recordings of 20 children with a median age of 7.5 (0.5-16.5) years were analyzed. Scoring of apneas according to the American Academy of Sleep Medicine (AASM) guidelines using nasal pressure, oronasal thermal sensor and respiratory efforts by means of respiratory inductance plethysmography (RIP), was compared to a scoring using the PneaVoX sensor and nasal pressure, without the oronasal thermal sensor nor RIP, during a dual blind study. RESULTS: The percentage of sleep time recording without artifacts was 97%, 97%, 87%, 65%, and 98% for the respiratory flow and SSP from the PneaVoX sensor, oronasal thermal sensor, nasal pressure, and RIP, respectively. As compared to the AASM scoring with RIP, sensitivity and specificity of the SSP for the scoring of central apneas were 75% and 99% for the first reader, and 70% and 100% for the second reader, respectively. Sensitivity and specificity for the scoring of obstructive apneas were 98% and 75%, and 100% and 70%, respectively. A significant number of apneas scored as central by RIP were scored as obstructive by the SSP. CONCLUSIONS: The PneaVoX sensor has a high degree of scorability in children. The PneaVoX sensor is a useful adjunct for characterizing apneas. PMID- 27655467 TI - Obstructive Sleep-Disordered Breathing Is More Common than Central in Mild Familial Dysautonomia. AB - STUDY OBJECTIVES: In familial dysautonomia (FD) patients, sleep-disordered breathing (SDB) might contribute to their high risk of sleep-related sudden death. Prevalence of central versus obstructive sleep apneas is controversial but may be therapeutically relevant. We, therefore, assessed sleep structure and SDB in FD-patients with no history of SDB. METHODS: 11 mildly affected FD-patients (28 +/- 11 years) without clinically overt SDB and 13 controls (28 +/- 10 years) underwent polysomnographic recording during one night. We assessed sleep stages, obstructive and central apneas (>= 90% air flow reduction) and hypopneas (> 30% decrease in airflow with >= 4% oxygen-desaturation), and determined obstructive (oAI) and central (cAI) apnea indices and the hypopnea index (HI) as count of respective apneas/hypopneas divided by sleep time. We obtained the apnea-hypopnea index (AHI4%) from the total of apneas and hypopneas divided by sleep time. We determined differences between FD-patients and controls using the U-test and within-group differences between oAIs, cAIs, and HIs using the Friedman test and Wilcoxon test. RESULTS: Sleep structure was similar in FD-patients and controls. AHI4% and HI were significantly higher in patients than controls. In patients, HIs were higher than oAIs and oAIs were higher than cAIs. In controls, there was no difference between HIs, oAIs, and cAIs. Only patients had apneas and hypopneas during slow wave sleep. CONCLUSIONS: In our FD-patients, obstructive apneas were more common than central apneas. These findings may be related to FD-specific pathophysiology. The potential ramifications of SDB in FD-patients suggest the utility of polysomnography to unveil SDB and initiate treatment. COMMENTARY: A commentary on this article appears in this issue on page 1583. PMID- 27655468 TI - A new socioeconomic status measure for vaccine research in children using individual housing data: a population-based case-control study. AB - BACKGROUND: We recently developed HOUSES, an individual housing-based socioeconomic status (SES) measurement for health disparities research. We assessed whether HOUSES was associated with risk of pertussis and pertussis vaccine up-to-date status in children. METHODS: The study utilized a previous population-based case-control study cohort assembled during the 2004-2005 pertussis outbreak. We collected data on pertussis vaccine status (up-to-date status) at the time of the index date. Using a z-score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated in continuous variable and categorized into quartiles. Vaccine up-to-date status was compared among subjects with different SES as measured by HOUSES using a chi square test and logistic regression models. RESULTS: Of the 391 eligible pediatric subjects (median age of 13.1 years with male sex of 55 %), 363 (93 %) were successfully geocoded to formulate HOUSES index. HOUSES was not associated with the risk of pertussis (p = 0.82). Pertussis vaccine up-to-date statuses were 79, 86, 83, and 94 % for children in the first (the lowest SES), second, third, and fourth quartiles of HOUSES, respectively (p = 0.03). HOUSES as a continuous variable was associated with pertussis vaccine up-to-date status (adjusted OR: 1.15 per increment of one unit of HOUSES, 95 % CI: 1.04-1.27, p = 0.008). CONCLUSION: While HOUSES is not associated with the risk of pertussis, it predicts vaccine up-to-date status among children with different SES. HOUSES may be a useful tool for vaccine delivery research among children. PMID- 27655469 TI - Predictors of Neurological Outcome of Tuberculous Meningitis in Childhood: A Prospective Cohort Study From a Developing Country. AB - AIMS: To assess the long-term outcome of childhood tuberculous meningitis treated with modern 4-drug antitubercular regimens and to determine predictors of survival and morbidity. METHODS: In this single-center prospective cohort, outcome of children with tuberculous meningitis treated with standard regimens was assessed at 6 months and 12 months after discharge using the Pediatric Cerebral Performance Category Scale. RESULTS: Of 130 children, 38 died in hospital and 34 were either severely disabled or comatose/vegetative at discharge. At 6 and 12 months, 87% of the survivors were either normal (n = 62) or mildly disabled (n = 17, on the Pediatric Cerebral Performance Category scale). On multivariate analysis, the factors associated with poor outcome at 12 months were stage III at admission (adjusted odds ratio 4.4, 95% confidence interval, 1.7-11.2, P = .002) and presence of infarcts on neuroimaging (adjusted odds ratio 2.6, 95% confidence interval, 1.1-6.6, P = .037). CONCLUSIONS: Despite the high in-hospital mortality, in resource-constraint settings, the survivors showed remarkable improvement, with two-thirds returning to a normal functional status at 6 months' follow-up. PMID- 27655470 TI - NeuroDebian Virtual Machine Deployment Facilitates Trainee-Driven Bedside Neuroimaging Research. AB - Freely available software, derived from the past 2 decades of neuroimaging research, is significantly more flexible for research purposes than presently available clinical tools. Here, we describe and demonstrate the utility of rapidly deployable analysis software to facilitate trainee-driven translational neuroimaging research. A recipe and video tutorial were created to guide the creation of a NeuroDebian-based virtual computer that conforms to current neuroimaging research standards and can exist within a HIPAA-compliant system. This allows for retrieval of clinical imaging data, conversion to standard file formats, and rapid visualization and quantification of individual patients' cortical and subcortical anatomy. As an example, we apply this pipeline to a pediatric patient's data to illustrate the advantages of research-derived neuroimaging tools in asking quantitative questions "at the bedside." Our goal is to provide a path of entry for trainees to become familiar with common neuroimaging tools and foster an increased interest in translational research. PMID- 27655471 TI - Intermediate Type of Obstetric Brachial Plexus Palsy. AB - Data of 829 infants with obstetric brachial plexus palsy were reviewed to identify any cases that could not be fitted into the any of the well-known types of palsy. These unusual cases were studied in detail with regard to clinical presentation and electrophysiological findings as well as management and spontaneous motor recovery. Erb's, extended Erb's, and total palsies were seen in 42.8%, 28.8%, and 28.0% of cases, respectively. Three cases (0.4%) did not fit into any of the classic types. One case had bilateral palsy, and the remaining 2 cases had unilateral palsy. All affected limbs presented with "abducted arms," "flexed forearms," and electrophysiological evidence of denervation of shoulder adductors and triceps. All cases had excellent spontaneous recovery within 6-12 months. It was concluded that these cases represent mild "intermediate" types of palsy in which the C7 root was the predominant site of injury. Good spontaneous recovery is expected. PMID- 27655472 TI - Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases. AB - Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES. PMID- 27655473 TI - Neurofibromatosis Type 2. AB - Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder (incidence 1:33 000-40 000) characterized by formation of central nervous system tumors, due to mutation in the NF2 gene on chromosome 22q12. Vestibular schwannomas are the hallmark lesion, affecting 95% of individuals and typically occur bilaterally. Schwannomas commonly occur on other nerves intracranially and in the spinal compartment, along with meningiomas, ependymomas, and gliomas. Although histologically benign, tumors are associated with significant morbidity due to multiple problems including hearing and vision loss, gait abnormalities, paralysis, pain, and seizures. Risk of early mortality from brainstem compression and other complications is significant. Severity of disease is higher when NF2 presents during childhood. Children have a more variable presentation, which can be associated with significant delays in recognition of the condition. Careful examination of the skin and eyes can identify important clinical signs of NF2 during childhood, allowing timely initiation of disease-specific surveillance and treatment. Monitoring for complications comprises clinical evaluation, along with functional testing including audiology and serial neuroimaging, which together inform decisions regarding treatment. Evidence for disease-specific medical treatment options is increasing, nevertheless most patients will benefit from multimodal treatment including surgery during their lifetime. Patient enrolment in international natural history and treatment trials offers the best opportunity to accelerate our understanding of the complications and optimal treatment of NF2, with a view to improving outcomes for all affected individuals. PMID- 27655474 TI - Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy. AB - Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. PMID- 27655476 TI - Health expenditures spent for prevention, economic performance, and social welfare. AB - BACKGROUND: Countries with limited resources in economic downturns often reduce government expenditures, of which spending on preventive healthcare with no apparent immediate health impact might be cut down first. This research aims to find the optimum share of preventive health expenditure to gross domestic product (GDP) and investigate the implications of preventive health services on economic performance and the population's wellbeing. METHODS: We develop the economic growth model to undertake health-economic analyses and parameterize for Taiwan setting. Based on the US experiences over the period from 1975 to 2013, this research further examines the model's predictions on the relationship between preventive health expenditure and economic performance. RESULTS: Theoretical analysis and numerical simulations show that an inverse U-shaped relationship exists between the proportion of GDP spent on prevention and social welfare, as well as between the proportion spent on prevention and economic growth. Empirical analysis shows an under-investment in prevention in Taiwan. The spending of preventive healthcare in Taiwan government was 0.0027 GDP in 2014, while the optimization levels for economic development and social welfare would be 0 . 0119 and 0 . 0203, respectively. There is a statistically significant nonlinear relationship between health expenditure on prevention and the estimated real impact of economic performance from US experiences. The welfare-maximizing proportion of preventive expenditure is usually greater than the proportion maximizing economic growth, indicating a conflict between economic growth and welfare after a marginal share. CONCLUSION: Our findings indicate that it is worthwhile increasing investment on prevention up until an optimization level for economic development and social welfare. Such levels could also be estimated in other economies. PMID- 27655475 TI - Are elderly and women under-represented in cardiovascular clinical trials? Implication for treatment. AB - Elderly and women have been often under-represented in randomised clinical trials testing the effect of treatments on cardiovascular diseases even though these diseases highly affect both of them.Compared to their younger counterparts elderly have a higher incidence of disease-related morbidities, take more medicines and account for more adverse drug-related events. Similarly women present several differences in pathophysiology, clinical manifestations and outcomes in comparison to their male counterparts. For these reasons the results of randomised clinical trials obtained in younger men cannot be simply translated in elderly and women and the conduction of research and clinical trials in these patient populations is a key aspect to acquire evidence-based knowledge in the understanding and management of their conditions and treatment.Although the under representation of elderly and women has been discussed for several years and several international guidelines or recommendation have been published to suggest how to improve the recruitment of these two populations, their recruitment is still insufficient. In particular, frail elderly and those with co-morbidities are not included questioning the external validity and the safety of most treatments.Aim of this review is to critically analyse how current recommendations for treatments of cardiovascular disease are not adequately devised for elderly and women. PMID- 27655477 TI - Validation of the Fitbit Zip for monitoring physical activity among free-living adolescents. AB - BACKGROUND: The widespread availability of affordable consumer-oriented devices for monitoring physical activity offers an appealing option to physical activity researchers, but studies are needed to demonstrate the validity and reliability of these products. To examine the validity of the Fitbit Zip, we recruited three cohorts (N's = 25, 35, and 27) of middle-school students to wear the Fitbit and the ActiGraph simultaneously for a week. Adolescents were healthy volunteers representing a range of activity levels. Mean daily minutes of MVPA and mean steps per day were compared between the Fitbit Zip and the Actigraph. RESULTS: The step data for the Fitbit Zip correlated highly with the step data yielded by the ActiGraph (r's = .72, .92, .96), and the MVPA data for the Fitbit Zip correlated highly with the MVPA data from the ActiGraph (r's = .67, .79, .94). Bland-Altman plots revealed that the Fitbit Zip overestimated activity in comparison to the ActiGraph, especially for Cohort One, which completed the study before Fitbit modified their algorithms to count as activity only bouts that continued for at least 10 min. CONCLUSIONS: Our data suggest that the Fitbit Zip is a reasonable alternative to the ActiGraph for estimating activity among free living adolescents. However, data from the Fitbit should not be used interchangeably with data from the ActiGraph, as there is a consistent tendency for the Fitbit to overestimate steps in comparison to the ActiGraph. Also, the findings confirm concern about using for research a consumer-oriented device that does not make public their algorithms. PMID- 27655478 TI - The differentiation of mammalian ovarian granulosa cells ? living in the shadow of cellular developmental capacity. AB - The mammalian cumulus-oocyte complex (COCs) promotes oocyte growth and development during long stages of folliculogenesis and oogenesis. Before ovulation, the follicle is formed by a variety of fully differentiated cell populations; cumulus cells (CCs) that tightly surround the female gamete, granulosa cells (GCs) and theca cells (TCs) which build the internal and external mass of the follicular wall. It is well documented that CCs surrounding the oocyte are necessary for resumption of meiosis and full maturation of the gamete. However, the role of the granulosa cells in acquisition of MII stage and/or full fertilization ability is not yet entirely known. In this article, we present an overview of mammalian oocytes and their relationship to the surrounding cumulus and granulosa cells. We also describe the processes of GCs differentiation and developmental capacity. Finally, we describe several markers of mammalian GCs, which could be used for positive identification of isolated cells. The developmental capacity of oocytes and surrounding somatic cells ? a ?fingerprint? of folliculogenesis and oogenesis. PMID- 27655479 TI - Microfluidic versus molecular assays - different approaches in assessing oocyte developmental competence. AB - In recent years, molecular techniques have brought about new solutions that focus on the developmental capacity of female oocytes and reproductive performance in the mammalian species. The developmental potency is the ability of oocytes to reach the MII stage following the long stages of folliculo- and oogenesis. The main proteins involved in this process belong to the connexin (Cx) family, which are responsible for the formation of gap junction (GJC) connections between the female gamete and surrounding somatic cells. The Cx are involved in bi directional transport of small molecules and are therefore responsible for correct oocyte-somatic cell nutrition, proliferation, and differentiation. However, the application of certain molecular techniques often leads to destabilization or destruction of the materials of interest, such as cells or whole tissues. Therefore, the applications of microfluidic methods, which are non invasive and quantitative, give new opportunities to further this area of biomedical research. Microfluidic research is based on real-time experiments that allow for control and/ or observation of the results during each step. The purpose of this review is to present both positive and negative aspects of molecular-microfluidic methods while describing the role of connexins in oocyte developmental capacity. PMID- 27655480 TI - Extracorporeal shock waves: perspectives in malignant tumor treatment. AB - Progress in basic research led to the design of new generations of anticancer drugs with some notable achievements. Over the years, more and more powerful drugs have been developed with the purpose of increasing the rate of response to therapy. As molecular power of chemotherapeutic agents increased, unfortunately also toxicity and undesired side-effects increased. The search for new therapeutic strategies to be used in the management of cancer is one of the more promising strategies to reduce chemotherapy toxicity. Extracorporeal Shock Waves (ESW), widely used for the treatment of urolithiasis, have been reported to cause modifications of cell growth both in vitro and in vivo. They exert an agonist cytotoxic effect with several chemotherapeutic agents, such as cisplatin, doxorubicin, bleomycin, paclitaxel. Moreover, as it has been reported that their main mechanism of action is an increase in cell membrane permeability, ESW are also used to deliver oligonucleotides and other small particles to cells. Recently, it was found that certain dye compounds, in particular porphyrins, can achieve a cytopathogenic effect when the disease site is subjected to ultrasound irradiation. This technique is referred to as sonodynamic therapy. Based on the new knowledge regarding the interaction between ultrasound with bulk liquid, several studies have shown a synergic effect of ESW and porphyrins in vitro, thus opening a new perspective in sonodynamic therapy, able to overcome some drawbacks encountered during conventional anticancer drug treatment. Finally, current advances in bioengineering encouraged the application of nano-scale technologies to medicine. Nanobubbles, composed of an external shell and a gas core, can deliver chemotropic drugs and porfirins, to target tumour tissues in response to physical triggers, and ESW features make them an ideal alternative to ultrasound in combination with drug-loaded nanobubbles in delivery strategies. PMID- 27655481 TI - ENOX2 (or tNOX): a new and old molecule with cancer activity involved in tumor prevention and therapy. AB - Cancer includes a number of related diseases due to abnormal cell proliferation that spreads to nearby tissues. Many compounds (physical, chemical and biological) have been used to try to halt this abnormal proliferation, but the therapeutic results are poor, due also to the side effects. It has been reported that ecto-nicotinamide adenine dinucleotide oxidase di-sulfide-thiol exchanger 2 (ENOX2), also known as tumor-associated nicotinamide adenine dinucleotide oxidase (tNOX), was found to be located on the cancer cell surface, essential for cancer cell growth. Capsaicin and other anti-oxidants are capable of inhibiting tNOX, causing apoptosis of cells, exerting anti-tumor activity. It is interesting that some authors reported that ENOX2 is present in the serum of cancer patients several years before the clinical symptoms of the tumor. However, this result has to be confirmed. In this article we discuss ENOX2 and its inhibition as a hope of improving cancer therapy. PMID- 27655482 TI - The effects of P. gingivalis and E. coli LPS on the expression of proinflammatory mediators in human mast cells and their relevance to periodontal disease. AB - Mast cells (MCs) are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions, including periodontal disease, through the release of cytokines, chemokines and proteolytic enzymes. Porhyromonas gingivalis (P. g) is widely recognized as a major pathogen in the development and progression of periodontitis. Here we compared the differential effects of lipopolysaccharides (LPS) from P. g and E. coli on the expression and production of tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP-1) by human MCs. Human LAD2 MCs were stimulated with LPS from either P. g or E. coli (1-1000 ng/ml). MCs were also stimulated with SP (2MUM) serving as the positive control or media alone as the negative control. After 24 h, the cells and supernatant fluids were collected and analyzed for beta-Hexosaminidase (beta-hex) spectrophotometrically, TNF, VEGF and MCP-1 release by ELISA and real-time polymerase chain reaction (PCR) for mediator gene expression, respectively. To assess the functional role of tolllike receptors (TRL) in mediator release, MCs were pre-incubated with either anti-TLR2 or anti- TLR4 (2 MUg/ml) polyclonal antibody for 1 h before stimulation with LPS. When MCs were stimulated with SP (2 MUM), there was a statistically significant beta-hex release as well as release of TNF, VEGF and MCP-1. Stimulation of MCs with either type of LPS did not induce degranulation based on the lack of beta hex release. However, both types of LPS stimulated expression and release of TNF, VEGF and MCP-1. Although, P. g LPS induced significant release of TNF, VEGF and MCP-1, the effect was not concentration-dependent. There was no statistically significant difference between the effects of P. g and E. coli LPS. P. g LPS stimulated TNF through TLR-2 while E. coli utilized TRL-4 instead. In contrast, VEGF release by P. g LPS required both TRL-2 and TRL-4 while E. coli LPS required TLR-4. Release of MCP-1 was independent of TLR-2 or TLR-4. P. g LPS activates human MCs to generate and release TNF, VEGF and MCP-1 through different TLRs than E. coli LPS. MCs may, therefore, be involved in the inflammatory processes responsible for periodontal disease. PMID- 27655483 TI - Obestatin directly controls chicken ovarian cell functions. AB - The aim of the present in-vitro study was to examine the role of obestatin in the direct control of basic avian ovarian granulosa cell functions ? proliferation, apoptosis and secretory activity. In addition, the effects of obestatin on hormone release by cultured ovarian granulosa cells and follicular fragments (containing both granulosa and theca cells) were examined. We identified the effect of obestatin addition (0.1, 10 or 100 ng/ml medium) on the accumulation of markers of proliferation (PCNA, cyclin B1, MAPK/ERK1,2) and nuclear (TdT) and cytoplasmic (bax, caspase 3) apoptosis, as well as the release of progesterone (P), testosterone (T) and estradiol (E) by cultured chicken granulosa cells. Furthermore, the action of obestatin addition (0.1, 10 or 100 ng/ml medium) on the release of P, T, E and argininevasotocin (AVT) by cultured fragments of chicken ovarian follicles was examined. The accumulation of proliferation and apoptosis markers was assessed by immunocytochemistry and SDS PAGE-Western immunoblotting. The release of hormones was determined by an EIA. It was observed that obestatin addition could inhibit the accumulation of proliferation markers (PCNA and cyclin B1, but not of MAPK/ERK1,2), promote the expression of nuclear (TdT) and cytoplasmic (bax, caspase 3) apoptosis markers and suppress P, T, and E release by cultured granulosa cells. In cultured ovarian follicular fragments, obestatin promoted P, T, and E, but not AVT, release. These observations represent the first demonstration that (i) obestatin can directly control avian ovarian cell proliferation, apoptosis and hormone release and (ii) the interrelationship between theca and granulosa cells can determine the characteristics of obestatin action on ovarian secretory activity. PMID- 27655484 TI - Evaluation of CD4+ CD25+ FoxP3+ regulatory T cells during treatment of patients with brucellosis. AB - Cell-mediated immunity (CMI) plays a critical role in the control of brucellosis. Regulatory T cells (Tregs) have a functional character in modulating the balance between host immune response and tolerance, which can eventually lead to chronic infection or relapse. The aim of this study was to assess the alteration of Tregs in cases of brucellosis before and after treatment. Thirty cases of acute brucellosis with the mean age of 41.03+/-15.15 years (case group) and 30 healthy persons with the mean age of 40.63+/-13.95 years (control group) were selected and assessed. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of all individuals. We analyzed the alteration of Treg cell count using flow cytometry for CD4, CD25, and FoxP3 markers. The level of CD4+ CD25+ FoxP3+ Treg cells was increased in active patients compared with controls (2.5+/-0.99% vs 1.6+/-0.84%, p= 0.0004), but it had declined in the treated cases (1.83+/-0.73%, p=0.02). The level of Tregs was elevated in three relapsed cases. The frequency of Tregs and Treg/Teff (effector T cell) ratio was correlated with inverse serum agglutination test (SAT) and, 2-mercaptoethanol (2-ME) titers as markers of treatment in brucellosis. Based on our findings, we suggest that regulatory cells, such as CD4+ CD25+ FoxP3+ Treg cells, may contribute to the development of infection processes involving immune responses in brucellosis, and evaluation of regulatory T-cell levels may be a potential diagnostic strategy for the treatment outcome in chronic and relapsed cases of brucellosis. PMID- 27655485 TI - ZNF185 inhibits growth and invasion of lung adenocarcinoma cells through inhibition of the akt/gsk3beta pathway. AB - Zinc finger (ZNF) proteins, a diverse family of proteins, have multiple biological functions in cancer. Increased expression of ZNF185 has been involved in the regulation of tumor growth and metastasis. However, the function and underlying mechanisms of ZNF185 in the tumorigenesis of lung adenocarcinoma (LAC) remain unclear. The protein expression of ZNF185 was examined in human LAC tissues by immunohistochemical assay. After lentiviral vector-mediated ZNF185 overexpression was infected into the LAC cell lines (A549 and LETPalpha-2), cell growth and invasive potential were respectively evaluated by MTT and Transwell assays. We found that the protein expression of ZNF185 was significantly downregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (37.10% vs 58.06%, P=0.015), and was negatively correlated with the lymph node metastasis of the LAC patients (P=0.005). Furthermore, overexpression of ZNF185 reduced cell proliferation and invasion in LAC cells, followed by the downregulation of p-AKT, p-GSK3beta, VEGF and MMP-9 expression. Taken together, our findings indicate that the decreased expression of ZNF185 is linked to the tumor metastasis in human LAC patients, and ZNF185 overexpression inhibits the growth and invasion of LAC cells through inhibition of the AKT/GSK3beta signaling, suggesting that ZNF185 may represent a potential therapeutic target for the treatment of LAC. PMID- 27655486 TI - Epithelialization and stromalization of porcine follicular granulosa cells during real-time proliferation - a primary cell culture approach. AB - The process of oocyte growth and development takes place during long stages of folliculogenesis and oogenesis. This is accompanied by biochemical and morphological changes, occurring from the preantral to antral stages during ovarian follicle differentiation. It is well known that the process of follicle growth is associated with morphological modifications of theca (TCs) and granulosa cells (GCs). However, the relationship between proliferation and/or differentiation of porcine GCs during long-term in vitro culture requires further investigation. Moreover, the expression of cytokeratins and vimentin in porcine GCs, in relation to real-time cell proliferation, has yet to be explored. Utilizing confocal microscopy, we analyzed cytokeratin 18 (CK18), cytokeratin 8 + 18 + 19 (panCK), and vimentin (Vim) expression, as well as their protein distribution, within GCs isolated from slaughtered ovarian follicles. The cells were cultured for 168 h with protein expression and cell proliferation index analyzed at 24-h intervals. We found the highest expression of CK18, panCK, and Vim occurred at 120 h of in vitro culture (IVC) as compared with other experimental time intervals. All of the investigated proteins displayed cytoplasmic distribution. Analysis of real-time cell proliferation revealed an increased cell index after the first 24 h of IVC. Additionally, during each period between 24-168 h of IVC, a significant difference in the proliferation profile, expressed as the cell index, was also observed. We concluded that higher expression of vimentin at 120 h of in vitro proliferation might explain the culmination of the stromalization process associated with growth and domination of stromal cells in GC culture. Cytokeratin expression within GC cytoplasm confirms the presence of epithelial cells as well as epithelial-related GC development during IVC. Moreover, expression of both cytokeratins and vimentin during short-term culture suggests that the process of GC proliferation is also highly associated with porcine ovarian follicular granulosa cell differentiation in vitro. PMID- 27655487 TI - Kruppel-like factor 2 suppresses growth and invasion of gastric cancer cells in vitro and in vivo. AB - Kruppel-like factor 2 (KLF2), a novel tumor-suppressor gene, is implicated in diverse cellular processes, including cell growth, apoptosis, and invasion. However, the role and action mechanisms of KLF2 in gastric cancer (GC) need be further elucidated. The expression of KLF2 was investigated by immunohistochemical assay in human GC tissues, and lentivirus-mediated KLF2 overexpression was transfected into GC cells (AGS and HGC-27) for assessing cell proliferation and invasion, respectively indicated by MTT and Transwell assays. Subcutaneous GC tumor models were constructed for estimating tumor growth in vivo. As a result, the expression level of KLF2 was decreased in GC tissues compared with the para-carcinoma tissues (31.03% vs 53.45%, P=0.035), and negatively correlated with the lymph node metastasis in GC patients (P=0.02). Moreover, overexpression of KLF2 inhibited the cell proliferation and invasive potential and downregulated the protein expression of PCNA, Bcl-2 and MMP-9 in GC cells. The result in vivo showed KLF2 overexpression reduced the xenograft tumor growth. In conclusion, our findings indicate that KLF2 may function as a tumor suppressor involved in the progression of human GC. PMID- 27655489 TI - Exposure to electromagnetic fields aboard high-speed electric multiple unit trains. AB - High-speed electric multiple unit (EMU) trains generate high-frequency electric fields, low-frequency magnetic fields, and high-frequency wideband electromagnetic emissions when running. Potential human health concerns arise because the electromagnetic disturbances are transmitted mainly into the car body from windows, and from there to passengers and train staff. The transmission amount and amplitude distribution characteristics that dominate electromagnetic field emission need to be studied, and the exposure level of electromagnetic field emission to humans should be measured. We conducted a series of tests of the on board electromagnetic field distribution on several high-speed railway lines. While results showed that exposure was within permitted levels, the possibility of long-term health effects should be investigated. PMID- 27655490 TI - Percutaneous coronary intervention for poor coronary microcirculation reperfusion of patients with stable angina pectoris. AB - Percutaneous coronary intervention (PCI) has been extensively applied to repair the forward flow of diseased coronary artery and can achieve significant curative results. However, some patients with acute myocardial infarction (AMI) develop non-perfusion or poor perfusion of cardiac muscle tissue after PCI, which increases the incidence of cardiovascular events and the death rate. PCI can dredge narrowed or infarct-related artery (IRA) and thus induce full reperfusion of ischemic myocardium. It is found in practice that some cases of AMI still have no perfusion or poor perfusion in myocardial tissue even though coronary angiography suggests opened coronary artery after PCI, which increases the incidence of vascular events and mortality. Therefore, to explore the detailed mechanism of PCI in treating coronary microcirculation of patients with stable angina pectoris, we selected 140 patients with stable angina pectoris for PCI, observing the index of microcirculatory resistance (IMR) of descending branch and changes of myocardial injury markers and left ventricular systolic function, and made a subgroup analysis based on the correlation between clinical indexes, IMR and other variables of diabetic and non-diabetic patients, PCI-related and non PCI-related myocardial infarction patients. The results suggest that IMR of anterior descending branch after PCI was higher compared to that before PCI, and the difference was significant (P less than 0.05); creatine kinase-MB (CK-MB), myohemoglobin and high sensitive troponin T were all increased after PCI, and the difference was also significant (P less than 0.05); brain natriuretic peptide (BNP) level became higher after PCI, with significant difference (P less than 0.05); left ventricular ejection fraction (LVEF) declined after PCI, and the difference before and after PCI was statistically significant (P less than 0.05). Moreover, subgroup analysis results of the three groups all demonstrated statistically significant differences. PCI can effectively increase microcirculatory resistance of patients with stable angina pectoris, especially those who develop both stable angina pectoris and diabetes. Patients with higher microcirculatory resistance before PCI are more likely to develop PCI-related myocardial infarction after PCI. PMID- 27655488 TI - Vitamins D3 and K2 may partially counterbalance the detrimental effects of pentosidine in ex vivo human osteoblasts. AB - Osteoporosis is a metabolic multifaceted disorder, characterized by insufficient bone strength. It has been recently shown that advanced glycation end products (AGEs) play a role in senile osteoporosis, through bone cell impairment and altered biomechanical properties. Pentosidine (PENT), a wellcharacterized AGE, is also considered a biomarker of bone fracture. Adequate responses to various hormones, such as 1,25-dihydroxyvitamin D3, are prerequisites for optimal osteoblasts functioning. Vitamin K2 is known to enhance in vitro and in vitro vitamin D-induced bone formation. The aim of the study was to assess the effects of Vitamins D3 and K2 and PENT on in vitro osteoblast activity, to convey a possible translational clinical message. Ex vivo human osteoblasts cultured, for 3 weeks, with vitamin D3 and vitamin K2 were exposed to PENT, a well-known advanced glycoxidation end product for the last 72 hours. Experiments with PENT alone were also carried out. Gene expression of specific markers of bone osteoblast maturation [alkaline phosphatase, ALP; collagen I, COL Ialpha1; and osteocalcin (bone-Gla-protein) BGP] was measured, together with the receptor activator of nuclear factor kappa-B ligand/osteoproteregin (RANKL/OPG) ratio to assess bone remodeling. Expression of RAGE, a well-characterized receptor of AGEs, was also assessed. PENT+vitamins slightly inhibited ALP secretion while not affecting gene expression, indicating hampered osteoblast functional activity. PENT+vitamins up-regulated collagen gene expression, while protein secretion was unchanged. Intracellular collagen levels were partially decreased, and a significant reduction in BGP gene expression and intracellular protein concentration were both reported after PENT exposure. The RANKL/OPG ratio was increased, favouring bone reabsorption. RAGE gene expression significantly decreased. These results were confirmed by a lower mineralization rate. We provided in vitro evidence that glycoxidation might interfere with the maturation of osteoblasts, leading to morphological modifications, cellular malfunctioning, and inhibition of the calcification process. However, these processes may be all partially counterbalanced by vitamins D3 and K2. Therefore, detrimental AGE accumulation in bone might be attenuated and/or reversed by the presence or supplementation of vitamins D3 and K2. PMID- 27655491 TI - Analysis of high risk factors for endoscopic retrograde cholangiopancreatography biliary metallic stenting after malignant duodenal stricture SEMS implantation. AB - The aim of this study was to explore the success rates and high risk factors for endoscopic retrograde cholangiopancreatography (ERCP) biliary metallic stenting after self-expandable metallic stent (SEMS) implantation in patients with malignant duodenal stricture. A retrospective cohort study was conducted. Forty two unresectable patients with malignant duodenal stricture who received endoscopic SEMS implantation between February 2012 and February, 2015 in the Department of Digestive Diseases of Xijing Hospital were enrolled in the study. These patients underwent subsequent ERCP biliary metallic stenting due to malignant biliary stricture. The clinical and iconography materials of these patients were retrospectively analyzed. ERCP biliary metallic stenting was successfully carried out on 71.4% of patients with previous malignant duodenal stricture SEMS implantation. In type 1 duodenal strictures 88% success rate of ERCP guided biliary decompression was obtained vs 18.2% success rate in Type 2 duodenal strictures. In both type 1 and 2 duodenal strictures of a length greater than 3.5 cm, ERCP was 44.4% successful vs 89% successful for strictures less than 3.5cm. Multiple regression analysis revealed that duodenal stricture length >=3.5 cm (OR, 9.85; 95% CI, 1.21-79.88) and 80 or 90 mm duodenal stent (OR, 17.03; 95% CI, 1.99-145.81) were independent risk factors for the failure of ERCP (biliary drainage or biliary decompression) in the patients with previous SEMS implantation. Moreover, duodenal stents of 60 mm had a higher success rate of 88%, vs 18.2% in 80-90 mm stents. Nevertheless, the success rates of type III strictures were 100%, including synchronous and asynchronous implantation of SEMS implantation and ERCP biliary metallic stenting. For unresectable malignant duodenal stricture patients with SEMS implantation, subsequent ERCP biliary metallic stenting was safe and effective. The length of malignant duodenal stricture, longer duodenal stents and type II duodenal stricture were high risk factors for the failure of ERCP biliary metallic stenting. PMID- 27655492 TI - Dynamics of monocyte surface receptors after burns: a pilot study. AB - Previous studies suggested that monocytes may play a vital role in infection and sepsis following burn injury. The aim of this study was to determine whether burn injury had any effect on the levels of expression of monocyte cell-surface receptors at different phases post burn injury. Ten adult burn victims with burns of >25% of the total body surface area were included in this study. Blood samples were collected on the first, third and seventh day post burn injury. The peripheral blood mononuclear cells were extracted, with or without lipopolysaccharide stimulation. The monocyte phenotypes of CD14, CD16, HLA-DR, CD163, TLR2 and TLR4 were characterized by flow cytometry. Six healthy volunteers were recruited as controls. The percentage of expressed CD14+ monocytes increased during the first day, and then decreased on the third and seventh day after burn injury. The percentages of CD14+ cells expressing CD16 and HLA-DR decreased on the first day, followed by an increase on the third and seventh day post burn. In comparison, the percentage of CD14+ monocytes expressing TLR2 and TLR4 was higher on the first day in burn patients than that of control participants, followed by no change on the third and seventh day post burn injury. There was no significant difference in the percentages of CD14+ expressing CD163 between the two groups. This study showed that the expression of the specific receptors on the surface of monocyte is affected by burn injury. The changes in the expression levels of these receptors may contribute to burn-induced infection susceptibility. PMID- 27655493 TI - Rosuvastatin alleviates the development of monocrotaline-induced pulmonary hypertension in rats. AB - Statins can increase endothelial function through enhancement of the expression and activity of endothelial nitric oxide synthase (eNOS). The aim of this study is to evaluate the effect of rosuvastatin on the number of circulating endothelial progenitor cells (EPCs) and endothelial expression of eNOS in monocrotaline-induced pulmonary hypertensive rats. Sixty Sprague-Dawley (SD) rats were divided into three groups of 20: control (group A), pulmonary hypertension (PAH) + rosuvastatin group (group B), and PAH (group C). Monocrotaline (MCT; 60 mg/kg) was injected (intraperitoneally) to induce PAH. Rats in group B received rosuvastatin [10 mg/(kg. day)] for 2 weeks. Peripheral blood (5 mL) was aspirated from the femoral artery of each rat before and after 2 weeks of treatment. Mononuclear cells were isolated and subcultured to obtain EPCs. Small and moderately sized pulmonary arteries were collected 2 weeks later for histological analyses. eNOS gene expression in endothelial cells of pulmonary arteries were then determined at mRNA and protein levels. eNOS expression at mRNA and protein levels and the number of circulating EPCs were reduced significantly in groups B and C compared with group A (P less than 0.05), and a significant difference between group B and group C (P less than 0.05) was observed. Vascular remodeling in small and moderately sized pulmonary arteries was attenuated markedly in group B compared with group C. These results suggest that rosuvastatin can ameliorate the remodeling of pulmonary arteries in MCT-induced PAH rats by increasing the number of circulating EPCs and eNOS upregulation. PMID- 27655494 TI - Hepatic fibrosis and supersonic shear imaging in patients with different etiological chronic hepatic diseases. AB - The objective of the present study was to investigate whether hepatic fibrosis difference of supersonic shear imaging (SSI) value existed in patients with different etiological chronic hepatic diseases. Retrospective analysis was used to study chronic hepatitis. All the subjects were diagnosed by shear wave elastography and percutaneous liver biopsy. The shear moduli were analyzed to check whether any difference existed between groups. For the chronic hepatitis B, autoimmune hepatitis and fatty hepatitis, the shear moduli in S0 stage were (8.50+/-3.1)kPa, (9.41+/-2.5)kPa, (8.97+/-3.8)kPa; the shear moduli in S1 stage were (9.54+/-3.0)kPa, (10.42+/-5.1)kPa, (9.51+/-4.6)kPa; the shear moduli in S2 stage were (11.77+/-4.8) kPa, (13.25+/-5.6)kPa, (11.03+/-6.0)kPa; the shear moduli in S3 stage were (14.96+/-6.1)kPa, (19.03+/-7.8) kPa, (15.38+/-7.8)kPa; the shear moduli in S4 stage were (20.36+/-7.5)kPa, (24.99+/-9.5)kPa, (19.53+/ 5.6)kPa. Shear wave elastography could measure the different etiological chronic hepatic diseases. PMID- 27655496 TI - Expressions of NDRG1, VEGF and Ki-67 in Condyloma Acuminatum. AB - The objective of this study was to explore the expressions and significance of NDRG1 (N-myc downregulated gene family 1), VEGF (vascular endothelial growth factor) and Ki-67 in lesions of Condyloma Acuminatum (CA). Immunohistochemistry was adopted to measure the expressions of NDRG1, VEGF and Ki-67 in 48 cases of CA and 18 normal skin controls. The positive rates of NDRG1, VEGF and Ki-67 were 63. 83.33% (40/48), 93.75% (45/48) and 85.42% (41/48) in the CA tissues, and 27.78% (5/18), 94.44%(17/18) and 61.11% (11/18) in the controls, respectively. The intensities of the expressions of NDRG1, VEGF and Ki-67 in CA tissues were significantly higher than those in the controls. There were significant differences both in the positive rates and the expression intensities of NDRG1, VEGF and Ki-67 between the two groups (P less than0.05). The Spearman?s Rank Order Correlation analysis indicated that the expressions of NDRG1 protein and VEGF protein were positively correlated by the Spearman?s Rank-Order Correlation analysis (r = 0.346, P=0.016). For the CA tissues with high expressions of NDRG1 and VEGF, NDRG1 and VEGF influenced both the occurrence and development of CA. PMID- 27655495 TI - Body composition in healthy older persons: role of the ratio of extracellular/total body water. AB - The aim of this study was to identify the best prognostic parameters for quickly assessing fluid volume status in the context of nutritional status and water balance in older persons and to facilitate decision-making of the general practitioner (GP). This pilot study was conducted with 142 volunteers aged 60 years or older who were Polish students of the University of the Third Age. Inclusion and exclusion criteria for the study were defined. Assessment tools included: the Mini Nutritional Assessment questionnaire (MNA(r)) and the anthropometric measurements. Weight and body composition analysis were determined by Bioelectrical Impedance Analysis (BIA) using the Tanita MC-780 multi frequency segmental Body Composition Analyzer. According to the MNA scale, 89.2% of the sample was wellnourished and 10.8% were at risk of malnutrition. A total of 47.1% participants had normal body mass index, 20.6% were overweight, and 32.3% were obese. The BIA showed that females had more fat mass (FM) compared to males (35.84% vs 23.90%), while men had more free fat mass (FFM) and total body water (TBW; 61.16% vs 45.22% and 53.31% vs 45.22%respectively). There were no statistically significant differences in FM, FFM, and TBW by age. The ratio of Extracellular to Total Body Water (ECW/TBW) was higher in women than in men (46.76% vs 43.66%). Of all measures, only ECW/TBW increased significantly with age and sex, especially after 65 years. We propose that ECW/TBW may be used as the first, simple, and fast indicator of water volume status in the context of nutritional status and water balance in older subjects. Systematic control of the ECW/TBW by GP or nurse may increase senior independence, resulting in longer self maintenance at home and reduced hospital admissions. PMID- 27655497 TI - Effect of tumor necrosis factor-induced protein 8 on T-cell-mediated immunity in mice after thermal injury. AB - Tumor necrosis factor-induced protein 8(TNFAIP8), the first identified member of the TNFAIP8 family, shares considerable sequence homology with members of this family. It is expressed in a wide variety of human normal tissues, with relatively higher levels in lymphoid tissues and placenta. The present study was designed to examine the effect of TNFAIP8 on T-cell-mediated immunity secondary to burn injury. Sixty male mice were randomly divided into four groups as follows: sham burn group, burn group, burn with TNFAIP8-siRNA transfection group, and burn with negative control transfection group, and they were sacrificed at designated time points. CD4+ T cells were isolated using MACS microbeads. T-Cell proliferation was analyzed with MTT assay, and IL-2, soluble IL-2R, IL-4, interferon-gamma (IFN-gamma) were determined with enzyme-linked immunosorbent assay kits. It was found that CD4+ T lymphocyte proliferative activity was significantly down-regulated when TNFAIP8 gene was silenced by siRNA in mice at 24 h post burn. Down-regulation of TNFAIP8 can significantly decrease expression levels of IL-2 and soluble IL-2R at 24 h after thermal injury. These results demonstrated that TNFAIP8 appeared to be involved in the immune regulation of CD4+ T lymphocytes, and the decreased expression of TNFAIP8 could affect T lymphocyte functions after thermal injury. PMID- 27655498 TI - Phytopharmacology of Tribulus terrestris. AB - Tribulus terrestris is an annual herb which belongs to the Zygophyllaceae family. This plant has been used in traditional medicine for the treatment of various diseases for hundreds of decades. The main active phytoconstituents of this plant include flavonoids, alkaloids, saponins, lignin, amides, and glycosides. The plant parts have different pharmacological activities including aphrodisiac, antiinflammatory, antimicrobial and antioxidant potential. T. terrestris is most often used for infertility and loss of libido. It has potential application as immunomodulatory, hepatoprotective, hypolipidemic, anthelmintic and anticarcinogenic activities. The aim of the present article is to create a database for further investigation of the phytopharmacological properties of this plant to promote research. This study will definitely help to confirm its traditional use along with its value-added utility, eventually leading to higher revenues from the plant. PMID- 27655499 TI - Effects of 10-hydroxycamptothecin on differentiation of RAW264.7 cells into osteoclasts. AB - This study was designed to investigate the effect of 10-hydroxycamptothecin (10 HCPT) on osteoclast formation. RAW264.7 cells were cultured in vitro with 100 ng/ml receptor activator for nuclear factor-kappa B ligand (RANKL) and 30 ng/ml recombinant macrophage colony stimulating factor (M-CSF), and 10-HCPT with different solubilities were added. After five-day cultivation, tartrate-resistant acid phosphatase (TRAP) staining was used to observe the number of osteoclasts. mRNA expression of osteoclast-specific genes, such as TRAP, cathepsin K (CTSK) and matrix metalloproteinase protease 9 (MMP-9), was detected by real-time Polymerase Chain Reaction (PCR). The effect of 10-HCPT on the proliferation activity of RAW264.7 cells was detected using Cell Counting Kit-8 (CCK-8). CCK-8 detection showed that 10-HCPT with a certain concentration (1 ng/ml to 5 ng/ml) had no effect on cell proliferation (P>0.05); 10-HCPT could inhibit the generation of osteoclasts. With the increase of the concentration of 10-HCPT, the number of osteoclasts generated from cells cultured with 10-HCPT [1 ng/ml (86+/ 11.14), 2 ng/ml (66.67+/-7.51), 5ng/ml (27.67+/-6.51)] was much lower than that of the control group (145+/-8.19), and the difference was statistically significant (all P=0, P less than 0.05); mRNA expression of osteoclast-specific gene TRAP [1 ng/ml (24.38+/-0.68), 2 ng/ml (20.09+/-1.86), 5 ng/ml (6.23+/ 0.53)], CTSK [1 ng/ml (10.08+/-0.81), 2 ng/ml (7.30+/-0.30), 5 ng/ml (3.20+/ 0.56)] and MMP-9 [1 ng/ml (43.54+/-6.96), 2 ng/ml (28.28+/-5.83), 5 ng/ml (11.07+/-2.53)] was much lower than that of the groups added with RANKL and M-CSF only (all P=0, P less than 0.05), and with the increase of concentration of 10 HCPT, the expression of osteoclast-specific genes showed a decreasing tendency. All the findings suggest that 10-HCPT can inhibit the formation of osteoclasts by reducing the expression of osteoclast-specific genes such as TRAP, CTSK and MMP 9. PMID- 27655500 TI - Radiotherapy of the neck and carotid stenosis. AB - The first choice of treatment for neck cancer is often radiotherapy. Therefore, we aimed to investigate the microinflammation after radiotherapy of the neck and the incidence of carotid stenosis. This study reports on patients treated with radiotherapy as part of the treatment for laryngeal cancer in the Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, P.R. China. Sixty-two males and nine females were treated with radiotherapy between 2006 and 3012. The carotid diameter was determined by measuring carotid intima media thickness (IMT) in the common, external and internal carotid artery. Microinflammatory conditions were assessed by high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor?alpha (TNF-alpha). Other studied risk factors included age, treatment modalities, radiation dose and energy, the height of the radiation field, and follow-up time. Carotid stenosis was detected in all of the 71 patients. It was mainly clinically unsuspected; 19 patients had sustained a vascular event (14 TIA, 5 CVI) at a median of 3.11 years (range 2.3?5.6 years) following RT. In four of five CVI patients, CVI occurred on the side of the irradiation. Eleven patients who suffered vascular incident had severe stenosis of the carotid artery and 6 had moderate (31-49% of the lumen). Only two patients with mild stenosis on the irradiated side suffered TIAs. Serum hs-CRP levels in carotid stenosis were 9.4 (+/-SD=5.97) mg/ml, IL-6 = 12.8 (+/ SD=2.62) pg/ml and TNF-alpha = 15.4 (+/-SD=4.49) ng/ml. The clinical detection of asymptomatic carotid stenosis is challenging, and current recommendations regarding the follow-up period should be scrutinized. PMID- 27655501 TI - Use of three-dimensional color power doppler in imaging of liver cancer. AB - We aimed to assess the role of three-dimensional color power Doppler (3D-CPD) imaging in diagnosis of liver cancer. First of all, we performed 2D- and 3D-CPD imaging on 96 cases of liver tumors with a total of 106 lesions to examine the characteristics of the vascular distribution patterns of the tumors, and in turn, compare the sensitivity and specificity. Also, with the use of three-dimensional volumetric measurement, we calculated the volume of tumors, quantity of intra tumor blood vessels, and the ratio of the quantity of intra-tumor blood vessels to tumor volumes (vascular index, VI). Finally, we statistically analyzed the vascular index between benign and malignant tumors. We found that the sensitivity/specificity were 21.3%/100% for 2D-CPD, and 81.3%/100% for 3D-CPD, based on the use of type-III of blood vessels for diagnosis of the malignant lesions. In 3D-CPD, the type-III of blood vessels along with VI of > 0.3/cm3 can be used as the criteria for the diagnosis of liver cancer since we found that average VI was 0.38/cm3 in 75 malignant tumors, but 0.18/cm3 in 31 benign tumors (p less than0.05). The sensitivity and specificity in determining malignancy in the liver based on VI > 0.3/cm3 were 78.7% and 87.1%, respectively. PMID- 27655503 TI - Investigation into early postoperative inflammatory small bowel obstruction by applying gastrointestinal decompression. AB - The objective of this study was to investigate early postoperative inflammatory small bowel obstruction (EPISBO) by applying gastrointestinal decompression to relieve abdominal distension. Thirty-six cases of patients were randomly divided into two groups: a control group (20 cases) and an observation group (16 cases). Routine continuous gastrointestinal decompression was assigned to the control group, while gastrointestinal decompression with dynamic and profound adjustment of the gastric tube and abdomen movement was assigned to the observation group, to induce abundant gastric juice and gas, and significantly relieve abdominal distension. A test was performed for each of the two groups to observe the relief time of the abdominal distension and the difference of abdominal girth of 5 cm before and after gastrointestinal decompression. Compared with the control group, the patients in the observation group with abdominal distension had earlier pain relief. More patients in the observation group had a difference of abdominal girth of 5 cm before and after gastrointestinal decompression. In gastrointestinal decompression, the method of dynamic and profound adjustment of the gastric tube and abdomen movement improve the effect of the gastrointestinal decompression, which relieves abdominal distention and promotes the postoperative recovery of organ functions. PMID- 27655502 TI - An ethnobotanical study of medicinal plants with narcotic, sedative and analgesic effects in west of Iran. AB - The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs. PMID- 27655504 TI - In vitro effect of IL-17D on human ovarian carcinoma cells and inherent immunity. AB - This study explored the expression of interleukin 17D (IL-17D) secreted by human ovariancarcinoma cells and the effect of exogenous IL-17D transfection on MICA, which is the ligand of NKG2D, on the surface of ovary carcinoma cells. Human ovarian papillary serous adenocarcinoma cell line SKOV3, empty vector control cell line SKOV3/vector, exogenous human IL-17D stable-transfected cell line SKOV3/IL-17D, as well as cisplatin (CDDP)-resistant cell SKOV/CDDP were cultured; ovarian adenocarcinoma cell line OVCAR-3, empty vector control cell line OVCAR3/vector and OVCAE3/IL- 17D were observed under a microscope. In the study, methyl-thiazolyl-tetrazolium (MTT) method was used to detect the inhibition rate, resistance index and proliferation of SKOV3 and SKOV3/CDDP. It was found that the expression of IL-17 D in SKOV3/CDDP was much higher than that of its parent cell line SKOV3; IL-17D might be correlated to the drug resistance of cells; the proliferation of SKOV3 transfected with IL-17D was significantly accelerated, indicating IL-17D may be effective in promoting the growth of oncocyte. PMID- 27655505 TI - Clinical effect of mechanical fragmentation combined with recombinant tissue plasminogen activator artery thrombolysis on acute cerebral infarction. AB - This study aims to explore the clinical effect of mechanical fragmentation combined with recombinant tissue plasminogen activator (rt-PA) artery thrombolysis on acute cerebral infarction (ACI). One hundred and thirty-two cases of ACI patients were randomly divided into an experimental group (66 patients) and a control group (66 patients). The experimental group was treated with mechanical fragmentation combined with rt-PA artery thrombolysis method, while the control group was treated with only the rt- PA artery thrombolysis method. All the patients had their basic information recorded. A computational analysis on National Institutes of Health Stroke Scale (NIHSS) scores, curative effect and bleeding data was carried out. The results showed that in the experimental group the curative effects were better and there were fewer complications. Accordingly, we conclude that mechanical fragmentation combined with rt-PA artery thrombolytic method is a safe and reliable therapy with significant curative effects. It improves the NIHSS scores of the patients markedly and reduces the incidence of subsequent pneumonia. PMID- 27655506 TI - Vitamin D and micro-inflammatory state in hemodialysis patients: a mini review and meta-analysis. AB - There is growing evidence that vitamin D (VitD) plays a role in the pathophysiological mechanism of every patient undergoing hemodialysis, and this role is significantly altered in a microinflammatory state. However, it is unclear whether supplementation dosage or route of administration should be altered due to this state. Thus, the objective of our mini review and meta analysis was to re-consider supplementation of VitD in HD patients exhibiting micro-inflammatory state. Pubmed, Web of Science and Google Scholar were searched up to January 19, 2016. We included studies that evaluated supplementation in HD patients with micro-inflammatory state. One reviewer extracted data and one reviewer verified the data accuracy. We qualitatively summarized the main results and meta-analyzed data on comparable outcomes across studies. The main outcome measures were serum levels of VitD. Ten eligible studies were published between 2002 and 2016, involving a total 1,239 patients. Average vintage of hemodialysis was 35.36 (+/-31.08) months. We identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials. The studies we reviewed provide some weak evidence to support VitD supplementation in patients on hemodialysis exhibiting micro-inflammatory state. We recommend that future trials focus on our main outcome measures (that is variable comparable across studies). PMID- 27655507 TI - Comparison of effects of 18F-FDG PET-CT and MRI in identifying and grading gliomas. AB - Glioma is the most common type of brain tumor. Malignant gliomas tend to have an increasingly higher incidence and are difficult to treat. Therefore, an accurate diagnosis of the grade of glioma before surgery is very important for planning surgery and determining prognosis. To compare the values of 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET-CT) and magnetic resonance imaging (MRI) for identifying and grading gliomas, we selected 70 patients who were diagnosed as having a primary glioma or suspected glioma at the People?s Hospital of Liaocheng in Shandong, China, and divided them into an observation group, which was examined by 18F-FDG PET-CT and a control group, which was examined by MRI. Image analysis, visual semi-quantitative analysis and qualitative analysis, follow-up and pathological results of the two groups were compared. Specificity, accuracy and sensitivity of brain MRI and PET-CT in grading the gliomas were calculated, and the results obtained were processed by Chi-squared test. Standard uptake value (SUV), SUVcorrect and L/WM (SUVmax ratio of a lesion to normal white matters in the opposite side) of FDG in the different grades of glioma were analyzed by single-factor variance analysis. Postoperative pathological detection confirmed 47 cases of glioma; the sensitivity, specificity and accuracy of PET-CT in grading glioma were all higher than those of MRI (P less than 0.05); the correlation between SUV and glioma grade, between SUVcorrect and glioma grade, and between L/WM and glioma had significant difference (P less than 0.05). Thus, it was concluded that 18F-FDG PET-CT performs better in diagnosing gliomas than MRI and is also more suitable for identifying different grades of glioma. PMID- 27655508 TI - Detection and study of plasma D-dimer change in patients with acute exacerbation of chronic obstructive pulmonary disease. AB - The purpose of this study was to observe the change in plasma D-dimer of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The patients were divided into three groups, i.e., AECOPD group, stable COPD group (COPD kept stable after treatment) and a healthy control group. The content of plasma fibrinogen (FIB) and D-dimer of all research subjects was detected and the difference between groups was analyzed. Moreover, pulmonary functions of patients in the AECOPD group and the stable COPD group, including forced expiratory volume in 1 second (FEV1%) and forced vital capacity rate of 1 second (FEV1/FVC), and blood gas (oxygen partial pressure (PO2) and partial pressure of carbon dioxide (PaCO2), were detected; and the differences between the two groups and the possible correlation were analyzed. Compared to the COPD stable group and the control group, the AECOPD group had a statistically significant higher content of plasma FIB and D-dimer (p less than 0.05); the content of plasma FIB and D-dimer of the COPD stable group was much higher than that of the healthy control group, but the difference had no statistical significance (p > 0.05); the content of D dimer of AECOPD patients was in a negative correlation with FEV1 and PO2 (p smaller than 0.05) and in a positive correlation with PCO2 (p smaller than 0.05). It can be concluded that D-dimer is correlated to the severity of AECOPD; hence, it can be used as an evaluation index for the severity of AECOPD. PMID- 27655509 TI - Non-surgical periodontal management in scleroderma disease patients. AB - The aim of the present study is to investigate the periodontal status of people with scleroderma and their response to non-surgical treatment protocol aimed at controlling the evolution of the disease. The response to non-surgical periodontal treatment was tested on patients belonging to a scleroderma group and a control group: the data show an improvement of the periodontal conditions of all these patients in response to treatment. When compared on the same diagram, a slight remission of the periodontal disease was obtained in both scleroderma and healthy patients. This highlights the benefit to soft tissues produced by non surgical periodontal treatment also in patients affected by systemic diseases. PMID- 27655510 TI - Standardization procedure for the nasal nitric oxide measurement method using Niox MINO(r) and the tidal-breathing technique with velum-closure. AB - Nitric oxide (NO) is a molecule that performs many functions in the human body. The entire respiratory tract can produce NO, but the highest production occurs in the upper respiratory tract, in the paranasal sinuses in particular. The aim of the present study was to assess a new nasal NO (nNO) measurement method using the Niox MINO Nasal(r) device (Aerocrine AB, Solna, Sweden) and a special procedure, in order to compare the nNO values obtained in 32 healthy subjects with the values found in the international literature. The measured normal nNO values were equal to 426.76+/-143.27 ppb, with a 95% confidence interval [160.22-733.30]. Males had an average nNO value equal to 446.76+/-133.63 [178.64 ? 714.02], whereas in females the average value was 403.80+/-154.90 [94.00-713.60]. This study allows us to confirm that we have been able to establish the normal range of nitric oxide quantity produced in the nasal/sinus cavities of healthy individuals using the Niox MINO Nasal(r) device and tidal-breathing with velum closure manoeuvre. PMID- 27655511 TI - Lights and shadows of dental implants: focus on mucositis and perimplantitis and their biological markers. AB - The increase in oral rehabilitation by means of dental implants has required an evolution of the related managing protocols and correct updating of the skills of dental professionals. Postsurgical management of the clinical case is aimed to stabilize the obtained results and preserve them from adverse conditions: a healthy implant prosthesis is maintained thanks to the huge number of consolidated protocols of oral hygiene. This practice plays a decisive role in the prevention of perimplant pathologies, forming a strong basis to ensure long implant life and avoid unnecessary and painful new surgical procedures. Furthermore, dental companies, in order to satisfy the new needs of professionals in oral hygiene, have produced new instrumentations and targeted drugs, in agreement to the cutting-edge scientific literature, thus creating a new market attracting huge interests in healthcare. The purpose of this topical review is to briefly comment on the state of the art of post-surgical dental implant management. This research is aimed to report the current protocols available to reduce the risk of oral diseases and prevent the progression of perimplant complications. Special focus has been dedicated to the most effective surgical and non-surgical protocols for treating mucositis and perimplantitis. PMID- 27655512 TI - Cytokine genotype distribution in patients with periodontal disease and rheumatoid arthritis or diabetes mellitus. AB - The association between oral and systemic health has highlighted the importance of periodontal health and treatment, with the consequence that dental assessment and attention to oral hygiene have assumed an increasingly important part in the clinical management of patients with diabetes mellitus and rheumatoid arthritis. The aim of this work was to assess genotype frequencies in polymorphisms of genes of IL-1alpha-889 and IL-1beta-511 in a case-controlled study population of patients affected by periodontal disease and rheumatoid arthritis or diabetes mellitus. PMID- 27655514 TI - A solitary uterine relapse in T-cell Acute Lymphoblastic Leukaemia: CT features and pathologic correlation. AB - T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis. PMID- 27655513 TI - Thyroid and shoulder diseases: the bases of a linked channel. AB - The association between thyroid disorders and musculoskeletal diseases has long been suspected, but it is still debated whether they have a role in the pathogenesis of shoulder diseases. In vivo and in vitro studies describe the role of thyroid hormones in bone, cartilage and tendon biology. Retrospective studies and case reports suggest that thyroid diseases should be considered as risk factors and hold prognostic value in some of the most common causes of shoulder pain. Thus, it is advisable to search for underlying thyroid disorders in these patients. The pathophysiologic mechanisms by which thyroid hormone imbalance affects the onset, progression and response to treatment of these diseases are yet to be thoroughly defined and demand further studies. PMID- 27655515 TI - Endometriosis and Glanzmann?s thrombasthenia. AB - Glanzmann?s thrombasthenia (GT) is a rare bleeding syndrome characterized by deficiency or defect of platelet aggregation complex. The pathogenesis of endometriosis is controversial but the strongest evidence leans towards retrograde menstruation. GT probably predisposes to endometriosis. The management of women affected by this disease can be difficult due to the risk of bleeding complications, especially during surgical treatment. We describe the cases of three sisters affected by endometriosis and GT, referred to our Department, who received different therapeutic management. PMID- 27655517 TI - Use of sodium hyaluronate and synthetic amino acid precursors of collagen for the symptomatic treatment of mucositis in patients undergoing haematopoietic stem cell transplants. AB - Oral mucositis (OM) may occur in up to 100% of patients undergoing condition regimen to hematopoietic stem cell transplant (HSCT). From the patient?s perspective, OM is one of the most debilitating side effects of transplantation. It is commonly thought that oral hygiene can modify the incidence and severity of oral mucositis, therefore professional oral health care (POHC) is recommended prior to conditioning regimen for HSCT. A new strategy for the treatment of OM is sodium hyaluronate (SH) combined with amino acid precursors of collagen (Aas) (Mucosamin(r)). SH is a mucoaderent polymer acting as a mechanical barrier and pain reliever. Furthermore, it allows prolonged contact of the product with the mucous membrane. In this study, a total of 68 adult patients due to undergo HSCT for allogenic and autologous transplant were enrolled at the Stem Cell Transplant Unit. The patients were divided into two groups. One group was treated with POHC before HSCT and applications of Mucosamin(r) during the recovery after transplantation. The second group served as controls, with the usual treatment of Clorexidine 0.20% adopted by the department. After HSCT the same clinician, an expert in oral medicine trained for the clinical trial, evaluated symptoms of the patients? mucositis of both groups every day. The treated patients developed less severe OM, therefore Mucosamin(r) seems to have a protective role against the more severe phases of mucositis. The maximum OM pain, measured with the VAS scale, was higher in patients who did not use Mucosamin(r). In the treated group OM resolved sooner than in the control group. PMID- 27655516 TI - Central apelin-13 administration modulates hypothalamic control of feeding. AB - The 77 amino prepropeptide apelin has been isolated from bovine stomach tissue and several smaller fragments, including apelin-13, showed high affinity for the orphan APJ receptor. The distribution of apelinergic fibers and receptors in the hypothalamus may suggest a role of apelin-13 on energy balance regulation, albeit the studies reporting the acute effects of apelin on feeding control are inconsistent. Considering the possible involvement of apelinergic system on hypothalamic appetite controlling network, in the present study we evaluated in the rat the effects of intrahypothalamic apelin-13 injection on food intake and the involvement of orexigenic and anorexigenic hypothalamic peptides and neurotransmitters. Eighteen rats (6 for each group of treatment) were injected into the ARC with either vehicle or apelin-13 (1-2 MUg/rat). Food intake and hypothalamic peptide and neurotransmitter levels were evaluated 2 and 24 h after injection. Compared to vehicle, apelin-13 administration increased food intake both 2 and 24 h following treatment. This effect could be related to inhibited cocaine- and amphetamine-regulated transcript (CART) gene expression and serotonin (5-hydroxytryptamine, 5-HT) synthesis and release, and increased orexin A gene expression in the hypothalamus. PMID- 27655518 TI - Probiotic mixture supplementation in the preventive management of trinitrobenzenesulfonic acid-induced inflammation in a murine model. AB - Inflammatory bowel diseases (IBD) are characterized by inflammatory conditions of the intestine. Probiotic bacteria (PB) can have beneficial effects in several gastrointestinal disorders. The objectives of this study were: (i) to provide an acute experimental IBD model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in CD-1 mice, and (ii) to assess the preventive effects of Citogenex (Lactobacillus casei and Bifidobacterum lactis) supplementation on intestinal tissues and microbiota. Mice were inoculated intrarectally with saline, ethanol or different TNBS solutions. 1%TNBS induced clinical signs of colitis (P less than 0.01) and histological damage (P less than 0.01). Based on these results, mice were pre-treated with Citogenex or saline for 1, 2 or 3 weeks before 1%TNBS treatment. Probiotic pre-treatment determined a reduction of clinical signs (P less than 0.05), histological alterations of colitis (P less than 0.05) and increased beneficial bacteria (P less than 0.05). This study confirms that TNBS induced colitis in CD-1 mice is useful for studying the mechanisms involved in IBD pathogenesis, and pre-treatment with Citogenex prevents the intestinal damage induced by TNBS. PMID- 27655519 TI - Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve. AB - The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging. PMID- 27655520 TI - Newborn screening of inherited metabolic disorders: the Italian situation. AB - Starting from an international overview of the current status of screening programs, the present paper focuses on the legal situation in Italy and the great differences among Italian regions. Since the introduction of tandem mass spectrometry (MS/MS) in the ?90s the paradigm ?one spot-one disease? changed. Only recently, some regions issued legislative acts to promote expanded newborn screening with MS/MS. This approach raises medico-legal and ethical issues because a fast neonatal diagnosis of an inborn error of metabolism (IEM) could increase chances of an early treatment and reduce disabilities, therefore citizens ought to have the same access to care countrywide. Enacting a mandatory standard for a disease screening panel using MS/MS and a few centers specialized in diagnosis, treatment and follow-up of patients affected by IEM (inborn errors of metabolism) can reduce legal and ethical issues. PMID- 27655521 TI - IgG4-related cranio-spinal hypertrophic pachymeningitis involving the internal auditory canal. AB - Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, which is a focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease, and cases involving the whole cervical spine are even rarer. Here, we describe a case of probable IgG4 related hypertrophic pachymeningitis involving the whole cervical spine and the auditory canals in an 18-year-old male. The patient, who had a history of paresthesia and had previously experienced weakness, presented with generalized tonic seizures. A decompressive laminectomy on cervical vertebrae was performed as a matter of urgency, removing intradural fibrous material. The patient responded well to treatment and was discharged walking independently, with no strength deficit to any of the 4 limbs, and with normal blood tests. PMID- 27655522 TI - Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial. AB - Although the role of homocysteine (HCys) in secondary cardiovascular prevention has been scaled down, hyper-homocysteinemia remains a risk factor for cerebrovascular events. The aim of this study was to investigate the efficacy of nutraceuticals in lowering HCys serum levels versus a conventional vitamin supplementation in hypertensive subjects at low cardiovascular risk. One-hundred and four patients (mean age 62.8+/-14.5 years, 63.5% males), 52 for each treatment group, were enrolled. The study recruited patients with stage 1 essential hypertension and hyper-homocysteinemia (HCys >=15 MUmol/L), without a history of cardiovascular and cerebrovascular disease. They were sequentially randomized to receive a combined nutraceutical containing 400 MUg folate-6-5 methyltetrahydrofolate, 3 mg vitamin B6, 5 MUg vitamin B12, 2.4 mg vitamin B2, 12.5 mg zinc and 250 mg betaine (Normocis400(r)) once daily for two months, or supplementation with highly dosed folic acid (5 mg/day) (control group). Differences in serum HCys values were compared by ANOVA for repeated measures. A significant HCys reduction in comparison to baseline was found in both groups at the end of the study treatment, from 21.5+/-8.7 to 10.0+/-1.7 MUmol/L for Normocis400(r) subjects (p less than 0.0001), and from 22.6+/-6.2 to 14.3+/-2.8 MUmol/L for controls (p less than 0.0001). HCys reduction was significantly higher among patients treated with Normocis400(r) (p less than 0.035). The ideal HCys level (i.e. less than 10 MUmol/L) was reached in 55.8% of cases in theNormocis400(r) group, and it was significantly higher than in controls. No side effects were observed in either treatment group. Randomized clinical trials are ongoing to test the effect of folate, B6, and B12 supplementation in primary prevention of cardiovascular and cerebrovascular events. In the meantime, especially when the ideal HCys level is far from being reached, Normocis400(r) appears to be safe, well tolerated and effective in reducing HCys levels. PMID- 27655523 TI - Neonatal oxidative stress depends on oxygen blood pressure in umbilical artery. AB - With advancing gestation, partial pressure of oxygen (pO2) and pH fall significantly. Hypoxia is a main factor inducing free radical generation and thereby oxidative stress (OS). Placental and fetal tissue response when oxygen becomes restricted is complex and partially known. We tested the hypothesis that changes in umbilical artery and vein blood gas concentrations modulate OS occurrence in the newborn. Seventy umbilical artery and vein plasma samples were collected from healthy term newborns immediately after delivery. F2 Isoprostanes (F2-Isop) were measured in all samples as reliable markers of lipid peroxidation. Significantly lower pCO2 and higher pO2 and pH were found in umbilical vein than in artery, as expected. A positive correlation was detected between pH and pO2 only in umbilical artery (p=0.019). F2-Isop levels were no different between artery and vein in cord blood. Significant correlations were found between F2 Isop and pCO2 (p=0.025) as well as between F2-Isop and pH in umbilical vein (p=0.027). F2-Isop correlated with pCO2 (p=0.007) as well as with pO2 values (p=0.005) in umbilical artery blood. Oxidative stress (OS) in newborns depends on oxygen concentrations in umbilical artery. OS biomarkers significantly correlate with pO2 and in umbilical artery but not in umbilical vein. In normoxic conditions fetal-maternal gas exchanges occurring in placenta re-establish normal higher oxygen levels in umbilical vein than artery, with a normal production of free radicals without any deleterious effects. PMID- 27655524 TI - Cultivated Sub-Populations of Soil Microbiomes Retain Early Flowering Plant Trait. AB - The collection of microorganisms found in the root zone of soil, termed the rhizosphere microbiome, has been shown to impact plant growth and development. Here, we tease apart the function of the cultivable portion of the microbiome from the whole microbiome in retaining plant traits modified through artificial selection on flowering time. Specifically, the whole microbiome associated with earlier flowering time of Arabidopsis thaliana was cultivated on four types of solid media to create cultivated fractions of the microbiome. These cultivated microbiomes were subsequently preserved in glycerol, frozen, and revived to yield a portion of the cultivable fraction to compare (1) whole microbiome, (2) cultivable microbiome, and (3) revived, cultivable microbiome controls on early flowering time. Plants grown in soils inoculated with bacteria grown on 25 % Luria broth and 10 % tryptic soy agar retained the early flowering trait. An increase in leaf biomass with two of the cultivated microbiomes (49.4 and 38.5 %) contrasted the lowered biomass effect of the whole microbiome. Inoculation with the cultivated microbiomes that were cryopreserved in glycerol showed no effect on flowering time or leaf biomass. The results indicate that the cultivable portion of a plant's microbiome retains the early flowering effect in A. thaliana, but cryopreservation of the cultivated microbiomes disrupts the microbial effects on flowering time. Furthermore, the contrasting effects on leaf biomass (an indirect response from selection on early flowering time), seen with the whole microbiome versus the cultivable portion, suggests versatility in using cultivation methods to modify multiple traits of plants. PMID- 27655525 TI - Glyceamic and insulinaemic response to mashed potato alone, or with broccoli, broccoli fibre or cellulose in healthy adults. AB - PURPOSE: To examine the role of realistic serving sizes of broccoli, broccoli fibre and cellulose co-consumed with mash potato, or mashed potato eaten alone, on glycaemic and insulinaemic responses (GR and IR) in healthy adults. METHOD: A non-blind randomized crossover trial was conducted with thirteen healthy subjects consuming four different meals. Capillary blood samples between 0 and 180 min were analysed for glucose and insulin. The incremental area under the fasting blood glucose and insulin curves (iAUC) was calculated for different time increments. Differences in GR and IR between meals were assessed by repeated measures analysis of variance. RESULTS: The immediate GR and IR to one serving of mashed potato eaten with two servings of broccoli were significantly lower than mashed potato eaten alone. The peak, incremental peak and iAUC0-30min for GR and iAUC0-30min for IR were all significantly lower for the broccoli-potato meal. This meal also takes longer to return to fasting baseline with a time-delayed lag in IR and GR compared to the potato only meal. The iAUC60-120min for IR was significantly greater for the broccoli-potato meal compared to the other meals. Yet there was no corresponding significant difference between the broccoli-potato meal and the other meals for peak, incremental peak IR or any other iAUCs for GR and IR. For the potato meals containing added broccoli fibre or cellulose, no significant differences in GR or IR were observed when compared with the potato eaten alone. CONCLUSION: Co-consumption of cooked broccoli with mashed potato has a significant effect on glycaemic and insulinaemic responses compared to potato eaten alone. Our study suggests broccoli eaten with potato improves glucose homeostasis and therefore indicates a general beneficial nutritional role for broccoli when eaten with a carbohydrate staple. PMID- 27655527 TI - Impact of a natural soil salinity gradient on fungal endophytes in wild barley (Hordeum maritimum With.). AB - Occurrence and distribution pattern of fungal endophytes in different tissues of halophytic plants across saline depressions are poorly studied. We investigated the endophytic fungal communities inhabiting roots, stems and leaves of Hordeum maritimum collected in a soil salinity gradient, i.e. non-saline, slightly saline and saline, using a culture-dependent approach. A total of 20 taxa belonging to Ascomycota phylum were identified by ITS rRNA gene sequence. Pyronema domesticum and Alternaria spp. were the most frequently isolated. Roots host higher diversity and were more frequently colonized by endophytes than aboveground organs. Endophytic composition of all organs surveyed differed according to salinity gradient. Contrary to expectations, the colonization rate of roots increased with soil salinity, indicating that under salt stress the endophyte plant association is promoted. All the isolates exhibited in vitro saline tolerance, especially those belonging to genera Xylaria, Chalastospora, Alternaria and Pyronema. Fungal tolerance to NaCl under in vitro conditions appears to be more dependent on the isolates than on the sites of their isolation, suggesting that under natural conditions other factors, beyond soil salinity, should be taken into account. These findings highlight the importance of fungal endophytes in the protection and/or adaptation of both interacting species (plant-fungus) to salt stress under natural conditions. PMID- 27655526 TI - Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete). AB - PURPOSE: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults. METHODS: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO). RESULTS: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge. CONCLUSIONS: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood. PMID- 27655528 TI - The response of aggregated Pseudomonas putida CP1 cells to UV-C and UV-A/B disinfection. AB - UV radiation is a spread method used worldwide for the disinfection of water. However, much of the research on the disinfection of bacterial cells by UV has focused on planktonic cells. Many bacterial cells in nature are present in clumps or aggregates, and these aggregates, which are more resistant to disinfection than their planktonic counterparts, can be problematic in engineered water systems. The current research used Pseudomonas putida (P. putida) CP1, an environmental and non-pathogenic microorganism which autoaggregates when grown under certain conditions, as a model organism to simulate aggregated cells. The study investigated the response of both the planktonic and the aggregated forms of the bacterium to UV-C (lambda = 253.7 nm) and UV-A/B (lambda > 300 nm) disinfection at laboratory scale in a minimal medium. The planktonic cells of P. putida CP1 were inactivated within 60 s by UV-C and in 60 min by UV-A/B; however, the aggregated cells required 120 min of UV-C treatment and 240 min of UV-A/B radiation to become inactive. The size of the aggregate was reduced following UV treatment. Although all the cells had lost culturability, viability as measured by the LIVE/DEAD(r) stain and epifluorescence microscopy was not completely lost and the cells all demonstrated regrowth after overnight incubation in the dark. PMID- 27655530 TI - Assessing Household Economic Vulnerability in HIV-Affected Communities in Five Regions of Cote d'Ivoire. AB - The objective of this study was to identify and describe levels of household economic vulnerability in HIV-affected communities in Cote d'Ivoire, defined as those with a high prevalence of HIV and large numbers of orphans and vulnerable children. We conducted a cross-sectional survey of 3,749 households in five health regions of Cote d'Ivoire. Using principal component analysis, we attempted to identify sets of correlated vulnerabilities and derive a small number of composite scores to create an index for targeting interventions to vulnerable populations. The 65 vulnerability measures examined did not cluster in ways that would allow for the creation of a small number of composite measures. Instead, we found that households face numerous unique pathways to vulnerability. PMID- 27655529 TI - Production of beta-xylosidase from Trichoderma asperellum KIF125 and its application in efficient hydrolysis of pretreated rice straw with fungal cellulase. AB - On-site cellulase and hemicellulase production is a promising way to reduce enzyme cost in the commercialization of the lignocellulose-to-ethanol process. A hemicellulase-producing fungal strain suitable for on-site enzyme production was selected from cultures prepared using wet disc-milling rice straw (WDM-RS) and identified as Trichoderma asperellum KIF125. KIF125 hemicellulase showed uniquely high abundance of beta-xylosidase in the xylanolytic enzyme system compared to other fungal hemicellulase preparations. Supplementation of Talaromyces cellulolyticus cellulase with KIF125 hemicellulase was more effective than that with the hemicellulases from other fungal sources in reducing the total enzyme loading for the improvement of xylose yield in the hydrolysis of ball-milling RS, due to its high beta-xylosidase dominance. beta-Xylosidase in KIF125 hemicellulase was purified and classified as a glycosyl hydrolase family 3 enzyme with relatively high specificity for xylobiose. The production of KIF125 beta xylosidase in the fermentor was estimated as 118 U/g-WDM-RS (2350 U/L culture) at 48 h. These results demonstrate that KIF125 is promising as a practical hemicellulase source to combine with on-site cellulase production using T. cellulolyticus. PMID- 27655531 TI - [Relationship between vitamin D deficiency and early-onset neonatal sepsis]. AB - OBJECTIVE: To evaluate the effect of vitamin D level on early-onset sepsis (EOS) in neonates. METHODS: Seventy-eight full-term neonates with EOS were used as the research group (EOS group). sixty healthy full-term neonates without clinical and/or laboratory features related to infections were used as the control group. Blood samples of the neonates and their mothers in both groups were collected within 72 hours of delivery to determine 25-hydroxyvitamin D(25-OHD) levels. The rate of vitamin D deficiency in the neonates and the level of 25-OHD supplemented to their mothers during pregnancy were compared between the two groups. RESULTS: There was a significant positive correlation between the serum level of 25-OHD of the mothers and that of the neonates in both groups (EOS group: r=0.797, P<0.01; control group: r=0.929, P<0.01). The neonates and their mothers in the EOS group had significantly lower 25-OHD levels than those in the control group (P<0.01). The rate of vitamin D deficiency among the neonates in the EOS group was significantly higher than that of the control group (P<0.01). The level of vitamin D supplemented to the mothers during the last 3 months of pregnancy in the EOS group was significantly lower than that in the control group (P<0.01). CONCLUSIONS: Low serum level of 25-OHD is associated with the development of early-onset sepsis in full-term neonates. PMID- 27655532 TI - [Effects of antibiotic stewardship on neonatal bloodstream infections]. AB - OBJECTIVE: To investigate the effects of antibiotic stewardship on the pathogen and clinical outcome of neonatal bloodstream infections (BSIs). METHODS: A retrospective study was performed on neonates with BSIs who were admitted to the neonatal ward in the years of 2010 (pre-stewardship) and 2013 (post-stewardship) for pathogens, antibiotic resistance, antibiotic use, and clinical outcomes. RESULTS: The admission rate of BSIs (6.47% vs 2.78%) and the incidence of nosocomial BSIs (0.70% vs 0.30%) in 2013 were significantly higher than in 2010 (P<0.01). However, there were no signicant differences in the clinical outcomes between the years of 2010 and 2013 (P>0.05). The four most common pathogens isolated from blood cultures, Staphylococcus haemolyticus, Staphylococcus epidermidis, Klebsiella pneumoniae ssp pneumoniae and E.coli, were similar between the two years. There were no significant differences in the detection rates of extended spectrum beta-lactamase-positve Klebsiella pneumoniae ssp pneumoniae or E.coli between the two years. The detection rates of methicillin resistant Staphylococcus/beta-lactamase-positive Staphylococcus haemolyticus and Staphylococcus epidermidis were similar between the two years (P>0.05). CONCLUSIONS: Since the implementation of antibiotic stewardship, there has been no marked variation in the common pathogens and their antibacterial resistance in neonatal BSIs. The antibiotic stewardship could promote the recovery of patients with BSIs. PMID- 27655533 TI - [Relationship between R236C site in exon 7 of SP-B gene and respiratory distress syndrome in Han newborns in western Inner Mongolia]. AB - OBJECTIVE: To detect and analyze the genetic variation in exon 7 of lung surfactant protein B (SP-B), and to investigate the relationship between the genetic variation and the incidence of neonatal respiratory distress syndrome (NRDS) in Han populations in western Inner Mongolia. METHODS: In the case-control study, 47 Han infants with NRDS were assigned to case group. All the 47 patients had the last three generations of their ancestors reside in western Inner Mongolia. Forty-seven Han newborns without NRDS were assigned to control group. PCR-based gene analysis was used to determine the mutation in exon 7 of SP-B gene and genotype and allele frequencies of the R236C site in exon 7 of SP-B gene. RESULTS: In Han newborns in western Inner Mongolia, there was no mutation in exon 7 of SP-B gene; two genotypes, CC and CT, were identified in the R236C site in exon 7 of SP-B gene. No TT genotype was found in the two groups. There were no significant differences in the genotype frequency of CC or CT as well as the allele frequency of C or T between the case and control groups (CC: 72% vs 85%, P>0.05; CT: 28% vs 15%, P>0.05; C: 85% vs 93%, P>0.05; T: 15% vs 7%, P>0.05). CONCLUSIONS: There is no mutation in exon 7 of SP-B gene in Han infants with NRDS in western Inner Mongolia. There is no significant association between the gene polymorphism of the R236C site in exon 7 of SP-B gene and the incidence of NRDS in Han populations in that region. PMID- 27655534 TI - [Current research status of drug therapy for apnea of prematurity]. AB - OBJECTIVE: To investigate the current status of studies on drug therapy for apnea of prematurity (AOP) in the past decade in China and abroad, and to describe the research trends in the field. METHODS: CNKI and MEDLINE were searched with the key words "apnea of prematurity" and "treatment" for articles published in the past decade (January 2006 to December 2015). The articles were screened and the key words were extracted to establish the co-occurrence matrix. Ucinet 6.2 was used to plot the knowledge map. RESULTS: A total of 26 Chinese key words and 20 English key words were included. Those in the center of the co-existent knowledge map of Chinses keywords were "preterm infants", "apnea", "primary apnea", "naloxone" and "aminophylline"; while "apnea", "preterm infants" and "caffeine" located in the central place of the co-existent knowledge map of English keywords. CONCLUSIONS: Methylxanthines are still the major drugs for AOP; however, aminophylline is mainly used in China, while caffeine is mainly used in foreign countries. Other drugs such as naltrexone are also used in the clinical treatment of AOP. PMID- 27655535 TI - [Influencing factors and evaluation indicators for asthma control level in children]. AB - OBJECTIVE: To investigate the influencing factors for asthma control level in children and the practicability of evaluation indicators for asthma. METHODS: A total of 185 children with asthma were enrolled. Questionnaires and pulmonary function test were used to evaluate the asthma control level and the factors influencing the control level. The correlation between evaluation indicators and asthma control level was analyzed. RESULTS: Among the 185 children with asthma, 139 (75.1%) achieved full control, 36 (19.5%) achieved partial control, and 10 (5.4%) had uncontrolled asthma. Application of inhaled corticosteroids and eosinophil count showed significant effects on asthma control level (P<0.05). There were significant differences in the percentage of forced expiratory volume in 1 second (FEV1%), fractional exhaled nitric oxide (FeNO), childhood asthma control test (C-ACT) questionnaire score, and pediatric asthma quality of life questionnaire (PAQLQ) score between the full control, partial control, and uncontrolled groups (P<0.05). In the children with asthma, FEV1% was positively correlated with C-ACT and PAQLQ scores (P<0.05), while there was no significant correlation between FEV1% and FeNO (P=0.214). CONCLUSIONS: Application of inhaled corticosteroids and eosinophil count are factors influencing asthma control in children. A combination of FEV1%, FeNO, C-ACT score, and PAQLQ score helps with the evaluation of asthma control level. PMID- 27655536 TI - [Application of ultrasonic cardiac output monitor in evaluation of cardiac function in children with severe pneumonia]. AB - OBJECTIVE: To study the clinical application of ultrasonic cardiac output monitor (USCOM) in evaluation of cardiac function in children with severe pneumonia. METHODS: Twenty-nine children with severe pneumonia were enrolled in the observation group and forty-three children with common pneumonia were enrolled in the control group. The USCOM was used to measure the cardiac function indices in the two groups. The results were compared between the two groups. The changes in cardiac function indices after treatment were evaluated in the observation group. ESULTS: The observation group had a significantly higher heart rate and significantly lower cardiac output, systolic volume, and aortic peak velocity than the control group (P<0.05). There were no significant differences in cardiac index or systemic vascular resistance between the two groups (P>0.05). In the observation group, the heart rate, cardiac output, systolic volume, aortic peak velocity, cardiac index, and systemic vascular resistance were significantly improved after treatment (P<0.05). CONCLUSIONS: The USCOM is a fast, convenient, and accurate approach for dynamic measurement of cardiac function and overall circulation state in children with severe pneumonia. The USCOM can provide a basis for diagnosis, treatment, and evaluation of the disease, which is quite useful in clinical practice. PMID- 27655537 TI - [Changes in blood CD4+CD25+ regulatory T cells in children with severe purulent meningitis]. AB - OBJECTIVE: To preliminarily study the changes in CD4+CD25+ regulatory T cells (Tregs) in children with severe purulent meningitis at the early stage and its possible implications. METHODS: A retrospective analysis was performed on the clinical data of 39 children with severe purulent meningitis who were admitted to the pediatric intensive care unit from August 2014 to December 2015. According to whether Tregs count was decreased within 12 hours of hospitalization (considering Tregs count <410/mm3 as decreased), they were divided into two groups: decrease group and non-decrease group. The associations between the changes in Tregs cells and the clinical manifestations, laboratory marker levels, and prognosis were analyzed. RESULTS: Of the 39 cases, 13 (33%) showed a decrease in the proportion of Tregs cells (<31%) and 18 (46%) showed a decrease in the absolute Tregs cell count (<410/mm3). Four deaths were all in the Tregs decrease group. Compared with the non-decrease group, the decrease group showed a significantly higher proportion of children with a peripheral blood leukocyte count lower than the normal range and a significantly greater increase in the level of serum procalcitonin (P<0.05). CONCLUSIONS: Tregs might be suppressed in children with severe purulent meningitis at the early stage. And its suppression could be related to the severer inflammation reaction and higher mortality in those patients. PMID- 27655538 TI - [Therapeutic effects of zinc supplement as adjunctive therapy in infants and young children with rotavirus enteritis]. AB - OBJECTIVE: To investigate the therapeutic effects of oral zinc supplement in infants and young children with rotavirus enteritis, and its preventive effects against diarrhea recurrence within 3 months after treatment. METHODS: A total of 103 infants and young children with rotavirus enteritis were randomly divided into zinc supplement group (n=51) and conventional treatment group (n=52). Both groups were equally treated with a comprehensive therapy, besides which the zinc supplement group received zinc gluconate granules for 10 days. The treatment outcomes were examined at 72 hours after treatment, and the time required for the disappearance of positive symptoms and the recovery of injured extra-intestinal organs were determined. In addition, these patients were followed up for 3 months to determine the incidence of diarrhea recurrence after treatment. RESULTS: The overall response rate in the zinc supplement group was significantly higher than that in the conventional treatment group (90% vs 75%; P<0.05). The durations of diarrhea, high fever, and vomiting in the zinc supplement group were significantly shorter than that in the conventional treatment group (P<0.05). In addition, the recurrence rate of diarrhea and the incidence of severe diarrhea within 3 months after treatment in the zinc supplement group were significantly lower than in the conventional treatment group (P<0.05). CONCLUSIONS: Oral zinc supplement as adjunctive therapy is effective in treating infants and young children with rotavirus enteritis, and reducing the incidence and severity of diarrhea recurrence in the subsequent 3 months. PMID- 27655539 TI - [Immunological mechanism of wheezing attack in children with cytomegalovirus infection]. AB - OBJECTIVE: To study the possible immunological mechanism of wheezing attack in children with cytomegalovirus (CMV) infection. METHODS: A total of 25 under-5 year-old children with wheezing following CMV infection were enrolled. The expression of serum regulatory T cells (Treg)/T helper 17 (Th17) cytokines interleukin (IL)-10, IL-6, and IL-17, and peripheral blood lymphocyte subsets were determined. Twenty age-matched healthy children were selected as the control group. RESULTS: The wheezing group had a significantly reduced serum IL-10 level, significantly increased IL-6 and IL-17 levels, significantly reduced levels of natural killer cells, and significantly increased levels of CD8+ T cells and CD19+ B cells, as compared with the control group. CONCLUSIONS: Wheezing children with CMV infection have Treg/Th17 imbalance and cellular immune dysfunction, which may be an important immunological mechanism of the development of wheezing in children after CMV infection. PMID- 27655540 TI - [Expression of Wif-1 and beta-catenin in the Wnt pathway in childhood acute lympho-blastic leukemia]. AB - OBJECTIVE: To investigate the expression and possible roles of Wnt inhibitory factor-1 (Wif-1) and beta-catenin in the Wnt pathway in childhood acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 35 children who had newly-diagnosed ALL and achieved complete remission on day 33 of remission induction therapy were retrospectively reviewed. The children before treatment were considered as the incipient group, and those who achieved complete remission on day 33 were considered as the remission group. Fifteen children with non malignant hematologic diseases were enrolled as the control group. RT-PCR was used to measure the mRNA expression of Wif-1 and beta-catenin. ELISA was used to measure the protein expression of Wif-1. RESULTS: Compared with the control and remission groups, the incipient group had significantly lower mRNA and protein expression of Wif-1 and significantly higher mRNA expression of beta-catenin (P<0.05). In the incipient and remission groups, high-risk children showed significantly higher mRNA expression of beta-catenin and significantly lower mRNA and protein expression of Wif-1 than the medium- and low-risk children (P<0.05). In the incipient and remission group, the children with T-cell acute lymphoblastic leukemia showed significantly higher mRNA expression of beta catenin and significantly lower mRNA and protein expression of Wif-1 compared with those with B-lineage acute lymphoblastic leukemia (P<0.05). In each group, there was a negative correlation between the mRNA expression of Wif-1 and beta catenin (P<0.05). CONCLUSIONS: Reduced expression of Wif-1 and increased expression of beta-catenin may be involved in the pathogenesis of childhood ALL, and the degree of reduction in Wif-1 and/or increase in beta-catenin may be related to prognosis. PMID- 27655541 TI - [Clinical phenotypes and copy number variations in children with microdeletion and microduplication syndromes: an analysis of 50 cases]. AB - OBJECTIVE: To investigate the association between genotype and phenotype of microdeletion and microduplication syndromes (MMSs) and the pathogenesis of pathogenic copy number variations (CNVs). METHODS: A total of 50 children with MMSs diagnosed by chromosomal microarray analysis (CMA) from June 2013 to September 2015 were enrolled, and the clinical manifestations and features of pathogenic CNVs were analyzed. RESULTS: The main clinical manifestations of children with MMSs included mental retardation, developmental delay, short stature, and unusual facies, with the presence of abnormalities in multiple systems. There were 54 pathogenic CNVs in total, consisting of 36 microdeletion segments and 18 microduplication segments, with sizes ranging from 28 kb to 48.5 Mb (mean 13.86 Mb). Pathogenic CNVs often occurred in chromosomes X, 15, and 1. CONCLUSIONS: The clinical manifestations of MMSs are not specific, and a genotype first approach can be used for diagnosis. Mode of inheritance, type of recombination (deletion or duplication), size of segment, and functional genes included helps with the interpretation of CNVs of de novo mutations, and in-depth research on rare pathogenesis may become breakthrough points for the identification of new MMSs. PMID- 27655542 TI - [A clinical analysis of gynecological diseases in 147 children]. AB - OBJECTIVE: To study the clinical features of gynecological diseases in hospitalized children. METHODS: A retrospective analysis was performed for the clinical data of 147 children with gynecological diseases who were hospitalized and treated in the department of gynecology. RESULTS: Among the 147 children, ovarian tumors were most common (53 cases, 36.1%), followed by reproductive tract dysplasia or malformation (29 cases, 19.7%), adolescent dysfunctional uterine bleeding (18 cases, 12.2%), traumatic injury in the vulva/vagina (15 cases, 10.2%), and vaginal foreign body (8 cases, 5.4%). The main symptoms of ovarian tumors included abdominal pain and abdominal or pelvic mass. Progressive abdominal pain was a main symptom in children with reproductive tract dysplasia or malformation. The children with adolescent dysfunctional uterine bleeding manifested as irregular or a lot of vaginal bleeding. The children with ovarian tumors and reproductive tract malformation or dysplasia were given surgical treatment, and those with adolescent dysfunctional uterine bleeding were given different sex hormones based on their clinical manifestations and endometrial thickness. Eight children with vaginal foreign body underwent hysteroscopy for vaginal examination, and the foreign body was successfully removed without the damage of the hymen. One patient with tubal pregnancy underwent laparoscopic tubal pregnancy debridement. One patient with hydatid mole was diagnosed with invasive hydatid mole after complete curettage of uterine cavity and then received chemotherapy. CONCLUSIONS: The top three gynecological diseases in children are ovarian tumors, reproductive tract dysplasia or malformation, and adolescent dysfunctional uterine bleeding. Common chief complaints of the patients include abdominal pain, abdominal masses, and irregular vaginal bleeding. Diagnosis and treatment should fully consider the physiological and reproductive features of children and give full play to the advantages of laparoscopy, hysteroscopy, and ultrasound. PMID- 27655543 TI - [Evaluation of nutritional status of school-age children after implementation of "Nutrition Improvement Program" in rural area in Hunan, China]. AB - OBJECTIVE: To investigate the nutritional status of school-age children in rural area in Hunan, China from 2012 to 2015 and to evaluate the effectiveness of the "Nutrition Improvement Program for Compulsory Education Students in Rural Area" (hereinafter referred to as "Nutrition Improvement Program"). METHODS: The nutritional status of school-age children aged 6-14 years was evaluated after the implementation of the "Nutrition Improvement Program" and the changing trend of the children's nutritional status was analyzed. The statistical analysis was performed on the monitoring data of the school-age children aged 6-14 years in rural area in Hunan, China from 2012 to 2015, which came from "The Nutrition and Health Status Monitoring and Evaluation System of Nutrition Improvement Program for Compulsory Education Students in Rural Area". RESULTS: In 2015, female students aged 6-7 years in rural area in Hunan, China had a significantly greater body length than the rural average in China (P<0.05). However, the other age groups had significantly smaller body length and weight than the rural averages in China (P<0.05). After the implementation of "Nutrition Improvement Program", the prevalence rate of growth retardation decreased (P<0.05), but the prevalence rate of emaciation increased (P<0.05). At the same time, the prevalence rate of overweight/obesity increased (P<0.05) and the prevalence rate of anemia decreased (P<0.05). CONCLUSIONS: The implementation of "Nutrition Improvement Program" has achieved some success, but the nutritional status of school-age children has not improved significantly. Overweight/obesity and malnutrition are still present. Therefore, to promote the nutritional status of school-age children it is recommended to improve the measures for the "Nutrition Improvement Program". PMID- 27655544 TI - [Fever, generalized pain, and multiple pulmonary nodules in a school-aged boy]. AB - A 9-year-old boy was admitted to Xiangya Hospital due to pain after trauma in the left lower limb for 5 days and fever with generalized pain for 2 days. The results of X-ray of the left lower limb were normal. Pulmonary computed tomography (CT) showed multiple pulmonary nodules in both lungs. Adrenal CT showed marked enlargement of the left adrenal gland. The patient also experienced generalized herpes and intermittent delirium and had a blood pressure up to 155/93 mm Hg. He was transferred to our hospital with a suspected diagnosis of pheochromocytoma. On admission, the patient had a blood pressure of 86/44 mm Hg, sporadic maculopapule and herpes, touch-evoked pain, exposure of superficial veins, white pus coating on the right side of the tongue, and tension in the abdominal muscle. No skin damage was observed in the left lower limb, and the patient was forced to be in the extending position and experienced significant swelling below the knees. Laboratory examination showed a reduction in platelet count, hypoproteinemia, a significant increase in creatase, a C-reactive protein level of 348 mg/L, and a procalcitonin level of >100 ng/mL. Thoracoabdominal and pelvic CT showed multiple patchy and nodular lesions in both lungs, which had an undetermined nature, as well as an enlarged spleen. The tests of puncture fluid from the left knee joint and the periosteum of the left tibia, blood culture, and bone marrow culture all showed methicillin-resistant Staphylococcus aureus. The patient was given anti-shock treatment, anti-infective therapy with vancomycin, debridement and continuous irrigation/drainage of osteomyelitis lesions in the left tibia, but the patient still experienced recurrent shivering and severe fever and increased subcutaneous and pulmonary nodules. Linezolid was added on day 8 after admission, and the patient's body temperature returned to normal on day 24 after admission. Subcutaneous and pulmonary nodules were gradually reduced and disappeared. The patient was treated for 2 months and then evaluated as cured. PMID- 27655545 TI - [Effects of umbilical cord blood mononuclear cells transplantation via lateral ventricle on the neural apoptosis and the expression of Bax and Bcl-2 proteins in neonatal rats with hypoxic-ischemic brain damage]. AB - OBJECTIVE: To explore the effects of umbilical cord blood mononuclear cells (UCBMC) transplantation on the neuronal apoptosis and the expression of Bcl-2 and Bax proteins in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into normal control (N)+normal saline (NS), HIBD+NS, N+UCBMC, and HIBD+UCBMC groups. HIBD model was prepared using the classical Rice-Vannucci method. Twenty-four hours after HIBD, UCBMC were transplanted in the N+UCBMC and HIBD+UCBMC groups. Seven days after transplantation, NeuN/Cleaved-Caspase-3 double immunofluorescence staining and TUNEL methods were used to observe neural apoptosis in the cortex. The expression levels of Bax and Bcl-2 proteins were examined by Western blot analysis. RESULTS: There were more NeuN+ cleaved Caspase-3+DAPI+ and TUNEL+DAPI+ cells in the HIBD+NS group compared with the N+NS and N+UCBMC groups (P<0.01). There were less NeuN+ cleaved Caspase-3+DAPI+ and TUNEL+DAPI+ cells in the HIBD+UCBMC group compared with the HIBD+NS group (P<0.01). The concentration of Bax protein was higher and that of Bcl-2 proteins was lower in the HIBD+NS group compared with the N+NS and N+UCBMC groups (P<0.01). The concentration of Bax protein in HIBD+UCBMC group was lower than that in the HIBD+NS group (P<0.01). The concentration of Bcl-2 protein was higher compared with the HIBD+NS, N+NS and N+UCBMC groups (P<0.05). CONCLUSIONS: UCBMC transplantation via lateral ventricle can upregulate the expression of Bcl-2 protein and down-regulate the expression of Bax protein, thus alleviating brain neural apoptosis in neonatal rats with HIBD. PMID- 27655547 TI - [Role of transient receptor potential vanilloid 1 in airway inflammation in asthmatic mice]. AB - OBJECTIVE: To study the effects of the change in transient receptor potential vanilloid 1 (TRPV1) channel activity on the degree of airway inflammation in asthmatic mice. METHODS: BALB/c mice were randomly divided into control, asthma, capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist), and dexamethasone groups. The asthmatic mouse model was established by intraperitoneal injection of mixed ovalbumin-aluminium hydroxide solution and ultrasonic atomization with OVA for sensitization and challenge. The capsaicin, capsazepine, and dexamethasone groups were given intraperitoneal injection of capsaicin (30 MUg/kg), capsazepine (10 MUmol/kg), and dexamethasone (2 mg/kg) respectively, at 30 minutes before challenge. Hematoxylin and eosin staining was used to observe the degree of pulmonary inflammation. ELISA was used to measure the content of interleukin-8 (IL-8) and interleukin-13 (IL-13) in bronchoalveolar lavage fluid (BALF). Real Time PCR was used to measure the relative content of TRPV1 mRNA in lung tissue. RESULTS: Compared with the asthma group, the capsazepine and dexamethasone groups showed reduced pulmonary inflammation, while the capsaicin group showed aggravated pulmonary inflammation. Compared with the control group, the asthma and capsaicin groups showed increases in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). Compared with the asthma group, the capsazepine and dexamethasone groups showed reductions in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). The capsaicin group showed increases in the content of IL-13 and IL-8 in BALF (P<0.05). CONCLUSIONS: TRPV1 channel agonist and antagonist can influence the degree of airway inflammation in asthmatic mice. Dexamethasone may reduce airway inflammation through regulating TRPV1 level. PMID- 27655546 TI - [Association between endoplasmic reticulum stress pathway mediated by inositol requiring kinase 1 and AECII apoptosis in preterm rats induced by hyperoxia]. AB - OBJECTIVE: To study the association between endoplasmic reticulum stress (ERS) pathway mediated by inositol-requiring kinase 1 (IRE1) and the apoptosis of type II alveolar epithelial cells (AECIIs) exposed to hyperoxia. METHODS: The primarily cultured AECIIs from preterm rats were devided into an air group and a hyperoxia group. The model of hyperoxia-induced cell injury was established. The cells were harvested at 24, 48, and 72 hours after hyperoxia exposure. An inverted phase-contrast microscope was used to observe morphological changes of the cells. Annexin V/PI double staining flow cytometry was performed to measure cell apoptosis. RT-PCR and Western blot were used to measure the mRNA and protein expression of glucose-regulated protein 78 (GRP78), IRE1, X-box binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP). An immunofluorescence assay was performed to measure the expression of CHOP. RESULTS: Over the time of hyperoxia exposure, the hyperoxia group showed irregular spreading and vacuolization of AECIIs. Compared with the air group, the hyperoxia group showed a significantly increased apoptosis rate of AECIIs and significantly increased mRNA and protein expression of GRP78, IRE1, XBP1, and CHOP compared at all time points (P<0.05). The hyperoxia group had significantly greater fluorescence intensity of CHOP than the air group at all time points. In the hyperoxia group, the protein expression of CHOP was positively correlated with the apoptosis rate of AECIIs and the protein expression of IRE1 and XBP1 (r=0.97, 0.85, and 0.88 respectively; P<0.05). CONCLUSIONS: Hyperoxia induces apoptosis of AECIIs possibly through activating the IRE1-XBP1-CHOP pathway. PMID- 27655548 TI - [Effect of triggering receptor expressed on myeloid cells 2 overexpression on airway inflammation and remodeling in mice with allergic asthma]. AB - OBJECTIVE: To investigate the effect of triggering receptor expressed on myeloid cells 2 (TREM-2) overexpression on airway inflammation and remodeling in mice with asthma. METHODS: A total of 40 BALB/c mice were randomly divided into normal control, asthma, empty vector, and TREM-2 overexpression groups (n=10 each). Ovalbumin (OVA) sensitization and challenge were performed to establish the model of asthma. The mice in the control group were given normal saline, and those in the empty vector and TREM-2 overexpression groups were transfected with adenovirus vector and TREM-2 adenovirus, respectively. RT-PCR and Western blot were used to measure the expression of TREM-2, MMP-2, MMP-9, ADAM33, and ADAM8. Bronchoalveolar lavage fluid (BALF) was collected to perform cell counting and classification. ELISA was used to measure the total serum level of IgE and the levels of cytokines in BALF. RESULTS: Compared with the control group, the asthma group showed significant reductions in the mRNA and protein expression of TREM-2 (P<0.05), a significantly increased level of Th2 cytokine (P<0.05), and significantly increased numbers of total cells and classified cells. Compared with the asthma group, the TREM-2 overexpression group showed a significantly reduced level of Th2 cytokine (P<0.05), a significantly reduced level of IgE (P<0.05), and significantly reduced numbers of total cells and classified cells (P<0.05), as well as significantly downregulated expression of the inflammatory factors and growth factors MMP-2, MMP-9, TGF-beta1, ADAM8, and ADAM33 (P<0.05). CONCLUSIONS: TREM-2 overexpression significantly alleviates airway inflammation and airway remodeling in mice with asthma and may become a potential target for the prevention and treatment of childhood asthma. PMID- 27655550 TI - [Pertussis diagnosis: the limitation of the currently used criteria and the suggestion of Global Pertussis Initiative]. AB - It has been recognized that pertussis is a disease that affects all age groups. There are obvious limitations in the currently used diagnostic criteria with "one size-fits-all" definition, which is not advantageous to start individual treatment and perform strategies for preventing the transmission. Therefore, the expert group of Global Pertussis Initiative gives a suggestion for the diagnosis of pertussis. Based on the related published studies, the present article analyzes the limitations of the current criteria, and introduces the GPI's suggestion in detail. PMID- 27655549 TI - [Inhibitory effect of KyoT2 overexpression on proliferation and migration of airway smooth muscle cells in mice with asthma]. AB - OBJECTIVE: To investigate the effect of KyoT2 on the proliferation and migration of airway smooth muscle cells (ASMCs) in mice with asthma. METHODS: Ovalbumin (OVA) was used to establish the asthmatic model of airway remodeling in BALB/c mice. ASMCs were isolated and cultured, and primarily cultured ASMCs were used as the control group. The expression of KyoT2 in ASMCs was measured in the control and asthma groups. After the ASMCs from asthmatic mice were transfected with pCMV Myc (empty vector group) or pCMV-Myc-KyoT2 plasmid with overexpressed KyoT2 (KyoT2 expression group) for 48 hours, RT-PCR and Western blot were used to measure the mRNA and protein expression of KyoT2, the MTT assay and BrdU assay were used to measure the proliferation of ASMCs, and Transwell assay was used to measure the migration of ASMCs. Western blot was used to determine the effect of KyoT2 overexpression on the protein expression of RBP-Jkappa, PTEN, and AKT. RESULTS: Compared with the control group, the asthma group had significantly downregulated expression of KyoT2 in ASMCs, and the KyoT2 expression group had significantly upregulated expression of KyoT2 in ASMCs (P<0.05). Compared with the empty vector group, overexpressed KyoT2 significantly inhibited cell proliferation and migration, downregulated the expression of RBP-Jkappa and AKT, and upregulated the expression of PTEN. CONCLUSIONS: Overexpressed KyoT2 can inhibit the proliferation and migration of ASMCs through the negative regulation of RBP-Jkappa/PTEN/AKT signaling pathway. PMID- 27655551 TI - [Recent progress in clinical research on pertussis]. AB - Pertussis is a highly contagious respiratory disease. Despite the high vaccination coverage, re-emergence of pertussis has been reported in many countries over the past two decades. With the increase in the incidence of pertussis, there has been a shift in the epidemiological features: an increased incidence of pertussis has been noted in older children and adults, who normally lack typical clinical manifestations, and who may be easily missed according to current diagnostic references for pertussis. In order to achieve better prevention and treatment of pertussis, this review article summarized the recent research progress in the epidemiology, clinical features, etiology, diagnosis, treatment, and prevention of pertussis, particularly focusing on the diagnosis of pertussis in older children and adults. PMID- 27655552 TI - [Research progress in relationship between fractional exhaled nitric oxide and asthma in children]. AB - Bronchial asthma is a heterogeneous disease that is characterized by airway hyperresponsiveness and chronic inflammation. It is often accompanied by reversible airflow obstruction. Current laboratory testing methods for the diagnosis of asthma in children mainly include lung ventilation function test. Due to the non-cooperation of children, it is very challenging to conduct lung ventilation function test for preschoolers. Lung function testing is an instantaneous indicator, which is influenced by the children's understanding ability and mental factors. In addition, it could not assess the severity of airway inflammation. Fractional exhaled nitric oxide (FeNO) is a noninvasive, simple, and objective indicator of airway inflammation and has gradually gained increased use in children in recent years. This review article introduces the source of FeNO, the reference value of FeNO in laboratory testing, and the progress in the application of FeNO in the diagnosis, prediction, and treatment of asthma in children of various ages. PMID- 27655553 TI - [Research progress of the application of probiotics in preterm infants]. AB - The gastrointestinal structure, function and immunity of preterm infants are immature. Furthermore the gastrointestinal microbe colonization is abnormal. Therefore the preterm infants are prone to a variety of gastrointestinal diseases. Probiotics can regulate gastrointestinal microbe constitute, improve gastrointestinal barrier function, reduce gastrointestinal inflammation response and regulate the immunity. At present, it is used for the prevention of necrotizing enterocolitis, late-onset sepsis, and feeding intolerance. The safety and efficacy of probiotics for preterm infants are still controversial. PMID- 27655554 TI - [Prevention and treatment of energy failure in neonates with hypoxic-ischemic encephalopathy]. AB - Hypoxic-ischemic encephalopathy (HIE) in neonates is the brain injury caused by perinatal asphyxia or hypoxia and is a major cause of death in neonates and nervous system dysfunction in infants and young children. Although to a certain degree, mild hypothermia therapy reduces the mortality of infants with moderate to severe HIE, it cannot achieve the expected improvements in nervous system dysfunction. Hence, it is of vital importance to search for effective therapeutic methods for HIE. The search for more therapies and better preventive measures based on the pathogenesis of HIE has resulted in much research. As an important link in the course of HIE, energy failure greatly affects the development and progression of HIE. This article reviews the research advances in the treatment and prevention of energy failure in the course of HIE. PMID- 27655555 TI - Effects of intermittent hypoxia on oxidative stress and protein degradation in molluscan mitochondria. AB - Oxygen fluctuations represent a common stressor in estuarine and intertidal environments and can compromise the mitochondrial integrity and function in marine organisms. We assessed the role of mitochondrial protection mechanisms (ATP-dependent and -independent mitochondrial proteases, and antioxidants) in tolerance to intermittent hypoxia or anoxia in three species of marine bivalves: hypoxia-tolerant hard clams (Mercenaria mercenaria) and oysters (Crassostrea virginica), and a hypoxia-sensitive subtidal scallop (Argopecten irradians). In clams and oysters, mitochondrial tolerance to hypoxia (18 h at 5% O2), anoxia (18 h at 0.1% O2) and subsequent reoxygenation was associated with the ability to maintain the steady-state activity of ATP-dependent and -independent mitochondrial proteases and an anticipatory upregulation of the total antioxidant capacity under the low oxygen conditions. No accumulation of end-products of lipid or protein peroxidation was found during intermittent hypoxia or anoxia in clams and oysters (except for an increase in protein carbonyl concentration after hypoxia-reoxygenation in oysters). In contrast, hypoxia/anoxia and reoxygenation strongly suppressed activity of the ATP-dependent mitochondrial proteases in hypoxia-sensitive scallops. This suppression was associated with accumulation of oxidatively damaged mitochondrial proteins (including carbonylated proteins and proteins conjugated with a lipid peroxidation product malondialdehyde) despite high total antioxidant capacity levels in scallop mitochondria. These findings highlight a key role of mitochondrial proteases in protection against hypoxia reoxygenation stress and adaptations to frequent oxygen fluctuations in intertidal mollusks. PMID- 27655556 TI - Validation of XMALab software for marker-based XROMM. AB - Marker-based XROMM requires software tools for: (1) correcting fluoroscope distortion; (2) calibrating X-ray cameras; (3) tracking radio-opaque markers; and (4) calculating rigid body motion. In this paper we describe and validate XMALab, a new open-source software package for marker-based XROMM (C++ source and compiled versions on Bitbucket). Most marker-based XROMM studies to date have used XrayProject in MATLAB. XrayProject can produce results with excellent accuracy and precision, but it is somewhat cumbersome to use and requires a MATLAB license. We have designed XMALab to accelerate the XROMM process and to make it more accessible to new users. Features include the four XROMM steps (listed above) in one cohesive user interface, real-time plot windows for detecting errors, and integration with an online data management system, XMAPortal. Accuracy and precision of XMALab when tracking markers in a machined object are +/-0.010 and +/-0.043 mm, respectively. Mean precision for nine users tracking markers in a tutorial dataset of minipig feeding was +/-0.062 mm in XMALab and +/-0.14 mm in XrayProject. Reproducibility of 3D point locations across nine users was 10-fold greater in XMALab than in XrayProject, and six degree-of-freedom bone motions calculated with a joint coordinate system were 3- to 6-fold more reproducible in XMALab. XMALab is also suitable for tracking white or black markers in standard light videos with optional checkerboard calibration. We expect XMALab to increase both the quality and quantity of animal motion data available for comparative biomechanics research. PMID- 27655557 TI - Editorial (Thematic Issue: Managing Strategies for Diverse Diseases: Challenges from Bench to Bedside Translation in Successful Drug Discovery and Development (Part C)). PMID- 27655558 TI - Molecular and ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East Mediterranean Area of Turkey. AB - This paper covers studies on the molecular and ecological aspects of G. glabra var. glandulifera, G. flavescens ssp. flavescens and G. echinata collected from Hatay (Turkey); with the aim to better understand their genetic variation and ecological requirements for possible conservation programs. The material including total genomic DNA was extracted by the CTAB, and for PCR reaction, a total of 14 SSR primers developed for Medicago truncatula were used. PCR amplifications were performed in a Multigen(r) Thermal Cycler. Soil samples were analysed for their texture, pH, total soluble salts, calcium carbonate, total N content, total phosphorus and organic matter content. In order to see the association between genetic, ecological and geographical data, a similarity matrix was generated. Genetic similarity distances between genotypes were correlated with those of Eucledian distances obtained from ecological and geographical data. Analysis of molecular variance (AMOVA) was performed using GenAlEx 6.5 software to determine variation among and within genetic variations. The genetic analysis showed that the highest expected heterozygosity values were obtained from G. glabra while the lowest were obtained from G. echinata. In general heterozygosity values were low, especially for G. echinata. Therefore, variation appears to be lower within each species than among three species. The physical and chemical analysis of soil and plant samples indicates that mineral accumulation in plants is substantially affected by the soil characteristics. There is a need for identification of better strategies for the improvement of varieties, especially for small farmers managing marginal soils. More studies should be conducted in order to safeguard these taxa, especially G. glabra var. glandulifera which is collected intensively due to its economic value, the same is true for endemic taxon G. flavescens ssp. flavescens. PMID- 27655560 TI - [Enhancing health management of chronic and non-communicable diseases to improve control effect of hypertension and high blood glucose]. AB - As the development of social economy, the change of life style, and the acceleration of population aging, hypertension and diabetes have become the major public health problems influencing people's health in China. The prevalence of hypertension and diabetes were in increase during the past few years, moreover, the burden of disease has become heavier than ever before. Although the awareness, treatment and control rates of hypertension and diabetes increased in recent years, compared with developed countries, the rates were still at low level. Therefore, it is necessary to enhance the population based comprehensive prevention and control of hypertension and diabetes. PMID- 27655559 TI - Photobiomodulation therapy in the management of chronic oral graft-versus-host disease. AB - AIM: Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) may experience oral complications associated with chronic graft-versus host disease (cGVHD). These complications may significantly affect quality of life, even many years post-HSCT. Current treatment options for oral cGVHD are limited and often include steroid or other immunomodulatory medications, which may not adequately control the oral condition. A non-immunosuppressive intervention for symptomatic relief in oral cGVHD would thus be a welcome addition to the treatment paradigm. MATERIALS AND METHODS: We report seven cases of oral cGVHD that were treated with photobiomodulation therapy (PBM), previously known as low-level laser therapy (LLLT). Patients underwent at least two PBM treatments per week in addition to local treatment with steroids, and if on systemic therapies, these were either unchanged or dosage was reduced during the period of PBM therapy. Follow-up data is presented for 4 weeks of treatment. RESULTS: Oral pain, sensitivity, and dry mouth improved in most patients. These findings suggest PBM therapy may represent an additional approach for management of oral cGVHD, and suggest that controlled studies should be conducted to confirm the efficacy and safety of PBM therapy in oral cGVHD and to determine optimal PBM therapy protocols. PMID- 27655561 TI - [Management of diabetes patients aged >=35 years in disease surveillance areas in China]. AB - Objective: To investigate the community-based management of diabetes patients aged >=35 years in China. Methods: The subjects from 2013-2014 Chronic Non communicable Disease and Risk Factor Surveillance in China were used in this study, those who were aged >=35 years and diagnosed by doctors in hospitals at community level or above were selected through clustering sampling. Questionnaire was used to collect the data of subjects' general information, health status, the treatment and the control of blood glucose. Blood samples were taken from the subjects to detect the fasting blood glucose level and blood glucose level at 2 hours after oral administration of glucosum anhydricum. The subjects were weighted according to complex sampling scheme to calculated the different rates and 95%CI. The Rao-scott chi2 test was performed to test the differences in rates between the subgroups. Results: The survey indicated that among the 10 056 diabetes patients aged >=35 years and diagnosed with diabetes, 4 609 received management service in communities. After being weighted, the management rate of diabetes patients was 45.0% (95% CI: 40.8%-49.2%). Females (46.9%, 95% CI: 42.8% 51.0%) had higher management rate than males (43.0%, 95% CI: 38.1%-47.9%). The management rate was higher in rural area (50.4%, 95%CI: 46.3%-54.5%) than in urban area (41.6%, 95%CI: 35.5%-47.6%). There was a significant age specific difference in the proportion of patients receiving management services (chi2=21.0, P<0.01), the rate of management was highest in the patients aged >=65 years (49.2%, 95%CI: 43.6%-54.7%), but lowest in the patients aged 35-44 years (35.2%, 95% CI: 27.9%-42.4%). The overall standardized management rate of diabetes patients in communities was 16.7% (95% CI: 13.7%-19.7%). The proportion of urban patients receiving standardized management service (19.7%, 95% CI: 15.3% 24.1%) was higher than that of rural patients (12.8%, 95% CI: 9.8%-15.8%). The overall treatment rate of diabetes patients in communities was 95.8% (95%CI: 94.8%-96.9%). The treatment rate was higher in females (97.0%, 95%CI: 96.0% 98.0%) than that in males (94.5%, 95%CI: 92.7%-96.4%). The control rate of blood glucose in diabetes patients receiving management in communities was 34.6% (95%CI: 31.5%-37.6%), and the highest blood glucose control rate was in the patients aged >=65 years (38.2%, 95%CI: 33.4%-43.0%), while the lowest blood glucose control rate was in the patients aged 45-54 years (34.4%, 95% CI: 26.7% 42.0%). Conclusions: Both the standardized management rate and blood glucose control rate were low in the diabetes patients aged >=35 years in China. It is necessary to strengthen the allocation of medical resources in communities and standardized diabetes management. PMID- 27655562 TI - [Prevalence of diabetes in adults in Hebei province]. AB - Objective: To understand the prevalence of diabetes in adults in Hebei province. Methods: The survey was conducted among the local residents aged >=18 years, who were selected through multi stage cluster sampling from September 2013 to April 2014. Design-based methods were used to analyze the prevalence in the last 12 months. Results: A total of 7 678 adults were included in the study. The overall prevalence of diabetes in Hebei was 12.9% (13.1% in men and 12.8% in women), there was no sex specific difference in diabetes prevalence (P=0.09). The prevalence was higher in urban residents (16.2%) than that in rural residents (12.1%), the difference was significant (P<0.01). The prevalence of diabetes increased with age (P<0.01). The prevalence of impaired fasting glucose was 5.1%, the difference was significant between men and women and between rural area and urban area (P<0.01). The prevalence of impaired glucose tolerance was 10.4%. The difference of prevalence of impaired glucose tolerance in men and women and between rural area and urban area was not significant. The rates of awareness, treatment and control of diabetes were 50.7%, 46.3% and 37.5%, respectively. Women had higher awareness rate and treatment rate of diabetes than men, the difference was significant (P<0.01). Conclusions: The prevalence of diabetes was high in adults in Hebei province, the difference in diabetes prevalence between urban area and rural area was significant. The prevalence of impaired fasting glucose and impaired glucose tolerance were high, but the rates of awareness, treatment and control of diabetes were low. PMID- 27655563 TI - [Practices and effects of different measures for blood pressure control in hypertension patients in Beijing, 2014]. AB - Objective: To understand the practices and effects of different measures for blood pressure control in hypertension patients. Methods: Patients who have known hypertension from the subjects of "2014 Beijing adult (aged 18-79 years) chronic diseases and risk factors survey" were selected. The choices of different hypertension control measures, the relationship between the measures and demographic characteristics of hypertension patients, and the effects of different control measures were analyzed. Results: A total of 2 229 known hypertension patients were included, the analysis was conducted through a questionnaire survey. Those who answered "never taking any measures" , "taking medication according to doctor's instructions" and "taking medication when blood pressure rose" accounted for 7.0%, 79.8% and 8.3%, respectively. Those who had "diet control" , "physical exercises" and "blood pressure monitoring" accounted for 22.4%, 23.7% and 22.1%, respectively. In terms of "taking medicine according to doctor's instructions" , women (84.3%), those aged >=60 years (87.6%), those living in urban area (81.5%), those living alone (83.8%), and Beijing local residents (82.3%) had higher compliance rates. As for "diet control" , women (24.4%), those aged >=60 years (25.8%) and those with educational level of college or above (29.5%) had better practices. In terms of "physical exercise" , those aged >=60 years (27.9%), those living in urban area (25.3%), those with educational level of college or above (32.5%) had better practice. Women (24.2%) and those aged >=60 years (28.4%) had higher "blood pressure monitoring" rate. More men (9.7%), those aged 18-44 years (14.7%), those with educational level of high school (9.3%), the unmarried (18.2%), and non-Beijing local residents (14.7%) answered "never taking any measure" , and in terms of "taking medication when blood pressure rose" , non-Beijing local residents (12.8%) had higher rate. In the field survey, more patients who never took any measure (98.1%) had higher blood pressure than those who took control measures (67.1%), and those who took medicine according to doctor's instructions had lowest blood pressure rise rate (63.9%). Conclusions: Most hypertension patients could take medication according to doctor's instructions, but less patients received other comprehensive intervention measures, and there were still some patients never took any control measure, or took medication only when blood pressure rose. "Taking medication according to doctor's instructions" showed a significant effect in blood pressure control. PMID- 27655564 TI - [Prevalence, awareness, treatment and control of hypertension in adults in Shandong province, 2013]. AB - Objective: To understand the prevalence, awareness, treatment and control of hypertension in adults in Shandong province in 2013. Methods: Adults aged >=18 were selected through multistage clustering sampling in 19 counties and districts in Shandong province. Design-based methods were adopted to analyze the prevalence, awareness, treatment and control of hypertension among local residents. Results: A total of 11 270 adults aged 18-69 years were surveyed, the prevalence of hypertension was 27.9% (31.4% in males, 24.3% in females) in Shandong province. The awareness rate of hypertension was 37.4% (34.7% in males, 41.0% in females), and the treatment rate of hypertension was 26.6% (23.4% in males, 30.7% in females). The treatment control rate of hypertension was 26.7% (28.3% in males, 25.1% in females) and the control rate of hypertension was 7.1% (6.6% in males, 7.7% in females). Conclusions: The prevalence of hypertension was high, but the awareness rate of hypertension, the treatment rate and the control rate of hypertension were low in adults in Shandong province. It is necessary to strengthen the health education about hypertension in young population, the prevention and control of hypertension in old population and those with low education level, the standardized management of hypertension cases and the reduction of risk factors for hypertension. PMID- 27655566 TI - [Prevalence and control status of diabetes in elderly community residents and risk factors]. AB - Objective: To analyze the prevalence and control status of diabetes in elderly community residents and related risk factors. Methods: A population-based cross sectional study was conducted in elderly community residents aged 60-95 years in an urban district of Beijing from September 2009 to June 2010 to collect the general health status of the elderly in the community, the prevalence of diabetes, medication treatment, and laboratory tests were conducted. Results: A sample of 2 102, including 848 males and 1 254 females, were selected through randomized clustering sampling for this study. Most participants had higher educational levels, and the smoking and drinking rates were low among them. The prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance were 24.8%, 2.5% and 30.6%, respectively. The awareness, treatment and control rates of diabetes were 78.5%, 69.3% and 15.9%, respectively. Multivariate logistic regression analysis showed that ORs of obesity, family diabetes history for diabetes were 1.42 (95%CI: 1.14-1.76) and 3.42 (95% CI: 2.70-4.35), respectively compared with control group. Also, obesity and family diabetes history were related risk factors for control status of diabetes. Conclusions: The prevalence of diabetes was relatively high, but the control rate was low in elderly community residents. Obesity, unhealthy lifestyles and family diabetes history were related risk factors. PMID- 27655565 TI - [Association between body mass index and risk of lung cancer in non-smoking males: a prospective cohort study]. AB - Objective: To assess the association between baseline body mass index (BMI) and risk of lung cancer in non-smoking males. Methods: A dynamic non-smoking male cohort was established on May, 2006. Baseline information on demography, lifestyle, such as smoking status and alcohol consumption, anthropometry, such as body height and weight, were collected during the baseline interview, and the information of newly-diagnosed lung cancer cases were also collected during the follow-up period. Multivariable Cox proportional-hazards regression model was used to analyze the association between baseline BMI and lung cancer in non smoking males. Results: By December 31, 2011, a total of 48 799 male non-smokers had been assessed in the study and there were 214 620.18 person-years of follow up and 4.40 years of average follow-up period. During follow-up, 198 lung cancer cases were identified among the 48 799 non-smoking males. Compared with those with normal BMI (kg/m2) (18.5<=BMI<24.0), the hazard ratio (95%CI) of lung cancer were 1.14(0.53-2.45), 0.57(0.41-0.78) and 0.61(0.38-0.97) for underweight (BMI<18.5), overweight (24.0<=BMI<28.0) and obese males (>=28.0), respectively, after adjustment for potential confounding factors, including age, education level, alcohol consumption, physical activity, history of diabetes and work environment. Baseline BMI was negatively associated with the risk of lung cancer in non-smoking males and the risk would be reduced by 22% (HR=0.78, 95% CI: 0.64 0.95) for per 5 kg/m2 BMI increase. The negative association between BMI and risk of lung cancer was significant among non-smoking males who aged >=50 years, and in those who had physical exercise <4 times/week, never drunk and worked above the coal mine, and for per 5 kg/m2 BMI increase, the risk of lung cancer would be reduced by 26%(HR=0.74, 95%CI: 0.60-0.92), 24%(HR=0.76, 95%CI: 0.62-0.95), 20% (HR=0.80, 95%CI: 0.65-1.00) and 23% (HR=0.77, 95%CI: 0.61-0.97), respectively. The result was similar after excluding the cancer patients newly diagnose within 1-year and their contribution person years. Conclusion: Baseline BMI might be negatively associated with risk of lung cancer in non-smoking males. PMID- 27655567 TI - [Relationship between hypertension and body mass index, waist circumference and waist-hip ratio in middle-aged and elderly residents]. AB - Objective: To assess the relationship between hypertension and BMI, waist circumference and waist-hip ratio in middle-aged and elderly residents in Luzhou, Sichuan province. Methods: A total of 2 033 middle-aged and elderly local residents aged 35-69 years were enrolled from Luzhou through stratified cluster sampling from March 27 to April 20, 2015. A face-to-face questionnaire survey and physical examination were conducted by trained investigators. Results: The overall prevalence rate of hypertension was 43.48%. The overweight rate, obesity rate, centrality obesity (calculated according to waist circumference) and centrality obesity (calculated according to waist-hip ratio) were 42.5%, 14.6%, 48.4% and 74.0%, respectively. The multivariate logistic analysis showed that gender and age were related to the prevalence of hypertension. Compared with age group <40 years, the OR values were 2.066 and 4.756 respectively in age groups 45 60 and >=60 years. After control the confounding effect of gender and age, overweight, obesity and centrality obesity (calculated according to waist circumference) were risk factors for hypertension, waist-hip ratio was not used in the regression equation. BMI and waist circumference or waist-hip ratio had combined effect on the prevalence of hypertension. Compared with the normal adults, the risk for hypertension increased as the increase of the level of overweight and obesity [OR from 1.524 (95%CI: 1.044-2.226) to 4.461 (95%CI: 3.405 6.326) and OR from 1.569 (95%CI: 1.134-2.171) to 5.468 (95%CI: 3.797-7.876)]. Conclusions: The influences of BMI, waist circumference and waist-hip ratio on the prevalence of hypertension were significant, but the influence of waist circumference on hypertension was greater than waist-hip ratio. Keeping normal bodyweight might be one of the effective hypertension prevention measures. PMID- 27655568 TI - [Effectiveness of health education about heat wave hazard prevention in the elderly: a mixed effect model analysis]. AB - Objective: To evaluate the effectiveness of health education about prevention of heat wave hazard in the elderly. Methods: A non-randomized controlled trial was conducted during the summer of 2015 among a sample of residents aged >=60 years in Panyu district, Guangzhou. Eight intervention measures for heat wave hazard prevention were taken in intervention group for 3 months (from August to October) and in control group no intervention measures were taken. The comparison of intervention effects was conducted between the intervention group and control group with mixed effect model after the collection of related information with same questionnaire. Results: After adjusting of family per capita income, family air-condition availability, alcohol use, disease history and time, the average score of risk awareness in the intervention group increased by 1.62, while it was 0.51 in the control group, the difference was significant (t=2.76, P=0.006). A significant effect was observed in the intervention group on the reduction of hospitalizations due to chronic diseases. The hospitalization rate due to chronic diseases in resent 3 months in the intervention group decreased from 32.39% (46/142) before intervention to 28.87% (41/142) after intervention; while in the control group, it increased from 26.28% (41/156) before intervention to 36.53% (57/156) after intervention. There was no significant difference between the two groups in awareness of knowledge on heat wave hazard prevention and the score of adaptation to heat wave. Conclusion: Health education programs could improve the risk awareness on heat waves, and reduce the hospitalizations due to chronic diseases in the elderly. PMID- 27655569 TI - [Current smoking status and awareness of tobacco hazard in adults in Beijing, 2014]. AB - Objective: To understand the status of current smoking and awareness of hazard in adults in Beijing, 2014. Methods: A total of 19 815 subjects were randomly selected with stratified multi-stage cluster sampling from 180 communities of 36 townships of 16 districts in Beijing. Each subject received a standardized questionnaire interview. Results: The current smoking rate of the adults was 26.6% (5 253/19 738), which was higher in men (52.2%) than in women (3.6%) and higher in suburb area (28.9%) than in urban area (25.0%). The adults aged 50-59 had higher rate of current smoking. The daily smoking rate was 23.7% (4 677/19 738). The average age when smoking started was 19.2 years. On average, one smoker consumed 15.2 cigarettes per day. The average score for smoking hazard awareness was 5.8, which was higher in smokers than in non-smokers (5.5 vs. 6.0) (t=-9.854, P=0.000). In the smokers, 5.7% (298/5 213) intended to give up smoking within one month. Doctors gave advice to stop smoking for 66.0% of current smokers. The current smoking rate of patients with chronic disease was 31.8% (3 703/11 628), and 5.5% (202/3 686) of them intended to stop smoking within one month. Conclusions: The smoking rate was still high in men in Beijing. The age of starting smoking every day decreased among younger people. The levels of awareness of tobacco hazard and passive smoking were still low. The willingness of smoking cessation was low. The rate of doctor giving smoking cessation advice was low. PMID- 27655570 TI - [Factors associated with smoking cessation attempts in male current smokers in rural area of Shandong province]. AB - Objective: To explore the influencing factors for the smoking cessation attempts in male current smokers. Methods: This cross-sectional study was conducted in nine villages selected from three counties (Pingyin, Junan and Liangshan) of Shandong province in August, 2010 through household questionnaire survey in villagers aged >=15 years to collect the information about current smokers demographic characteristics and smoking-related behaviors. A hurdle count data model was used to assess factors associated with the times of past smoking cessation attempts. Results: Among 1 798 male current smokers, 29.53% had at least one smoking cessation attempt. Smokers who were married (beta=0.705, P=0.002), had high educational level (beta=0.214, P=0.026) and had higher level of awareness of smoking risks (beta=0.237, P=0.009) were more likely to have smoking cessation attempt. Young age at smoking initiation (beta=-0.167, P=0.035) and higher level of awareness of smoking risks (beta=0.146, P=0.020) were associated with increased smoking cessation attempts. Conclusions: Less male current smokers had smoking cessation attemps in rural area in Shandong. The factors influencing smoking cessation attempt varied. It is necessary to conduct targeted intervention according to the smokers' smoking cessation experience. PMID- 27655571 TI - [Prevalence and trend of overweight and obesity in children and adolescents in Guangdong province, 2002-2012]. AB - Objective: To investigate the prevalence and trend of overweight and obesity in children and adolescents aged 6-17 years between 2002 and 2012 in Guangdong province. Methods: A total of 7 075 children and adolescents aged 6-17 years were selected in Guangdong for nutritional survey in 2002 and a total of 2 319 children and adolescents aged 6-17 years were selected in nine counties/districts of Guangdong for nutritional survey during 2009-2012 through multi-stage random cluster sampling. The body height and weight of all the children and adolescents were measured. Results: The result of 2009-2012 survey indicated the average prevalence of overweight and obesity in the children and adolescents surveyed were 7.3% and 4.5%, respectively. The prevalence of overweight and obesity were higher in boys (8.9% and 6.5%) than in girls (5.3% and 2.2%), in rural area (9.3% and 5.6%) than in urban area (4.7% and 3.2%). Children and adolescents aged 9-11 years had a higher overweight and obesity rates compared with other age groups. Compared with 2002, except for obesity rate in urban girls, the prevalence of overweight and obesity in children and adolescents obviously increased. The increase rate was higher in rural area than urban area and in boys than in girls. Conclusions: Compared with 2002, the prevalence of overweight and obesity in children and adolescents in Guangdong obviously increased. The prevalence was much higher in boys, those living in rural area and those aged 9-11 years, thus more attention should be paid to them. PMID- 27655572 TI - [Analysis on duplicate reporting of hepatitis B in national notifiable communicable disease report system in China, 2011-2013]. AB - Objective: To analyze the duplicated reporting of hepatitis B in the national notifiable communicable disease report system (NNDRS) in China during 2011-2013. Methods: The data of hepatitis B reported from January 1, 2011 to December 31, 2013 were collected from NNDRS, the duplicated reporting were searched with software SAS 9.1.3 according to the cases'ID number, name, gender, birth data and current address code. Results: During 2011-2013, a total of 3 389 374 hepatitis B cases were reported through NNDRS, but the duplicated reporting rate was 7.35% (249 047). According to 6 protocols, the duplicated reporting rate ranged from 0.88% to 6.38%. If using the data in 2011 as the baseline, the duplicated reporting rate in the three years was 2.91%, 8.11% and 11.72%, respectively. In the duplicated repeating, 33.04% (71 709) occurred in the same year, and 66.96% (145 329) occurred in other year. Without the duplicated repeating, the hepatitis B incidence in Xinjiang and Qinghai provinces in 2013 could decreased by 30.80/100 000 and 26.26/100 000, respectively. Conclusions: The analysis indicated that the duplicated repeating rate of hepatitis B was 7.36% in NNDRS during 2011-2013, and the duplicated reporting mainly occurred in other years. The duplicated reporting of hepatitis B in NNDRS had greatly affected the accuracy of surveillance data in some provinces, such as Xinjiang and Qinghai. PMID- 27655573 TI - [Etiology and drug resistance of non-typhi Salmonella in Henan province, 2011 2015]. AB - Objective: To analyze the serotypes and antibiotic resistance phenotypes of non typhi Salmonella strains in Henan province from 2011 to 2015. Methods: The stool samples were collected from diarrhea patients, and enriched with SBG enrichment broth and the pathogen isolation was conducted with CHROMAgar selective culture medium at 37 C for 18-24 hours using KIA/MIU biochemical action and API20E biochemical system slab to identify Salmonella strains. The serotypes of all the positive strains were detected with SSI Salmonella typing sera. According to K-B drug susceptibility testing method published by USA clinical and Laboratory Standards Institute (CLSI), the antibiotics resistant phenotype of the positive strains were analyzed. Results: A total of 1 351 strains of non-typhi Salmonella were isolated, in which 811 were from males, 540 were from females. The ratio of men to women was 1.5?1. Children and young adults were mainly affected. The pathogen isolation was mainly in May-October during a year. The 1 351 strains of non-typhi Salmonlla were divided into 58 serotypes. S. enteritidis, S. typhimurium, S. agona, S. derby, S. indiana, S. senftenberg and S. thompson ranked 1st-7th. The drug-resistance rate of the 1 351 strains was 46.1% to synthetic broad-spectrum penicillin ampicillin (AMP), 19.5% and 21.2% to the three generation cephalosporin ceftazidime (CAZ) and cefotaxime (CTX), 8.8% to the four generation cephalosporins cefepime (FEP), 58.7% to the one generation of quinolones nalidixic acid (NAL), 14.7% to the three generation fluoroquinolone ciprofloxacin (CIP) and norfloxacin (NOR), 25.0% and 35.6% to aminoglycoside antibiotic gentamicin (GEN) and streptomycin (STR), 35.4% to amphenicols (CHL), 31.7% to sulfonamide trimethoprim (TMP) and 37.8% to tetracycline (TET). Totally 879 strains were multidrug resistant (65.1%): 350 strains were resistant to 3-4 kinds of antibiotics (25.9%), 309 strains were resistant to 5-7 kinds of antibiotics (22.9%), 174 strains were resistant to 8-10 kinds of antibiotics (12.9%) and 48 strains were resistant to 11-12 kinds of antibiotics (3.6%). Conclusion: The serotypes of non-typhi Salmonella strains isolated from Henan province varied, some strains were resistant to 12 kinds of antibiotics commonly used in clinical treatment and the multidrug resistance has become serious. PMID- 27655574 TI - [Spatial-temporal analysis of pulmonary tuberculosis in Shandong province, 2015]. AB - Objective: To analyze the spatial-temporal epidemiological characteristics of active pulmonary tuberculosis (PTB) and sputum smear positive (SS+) PTB in Shandong province, China, 2015. Methods: The surveillance data of active PTB and SS+PTB in Shandong in 2015 were collected and analyzed by using the global and local indicators of spatial association (Moran's I) for the spatial autocorrelation of PTB, and by using SaTScan forspatial-temporal clustering characteristics of PTB based on geographic information system. Results: Totally, 31 776 active PTB cases and 8 631 SS+PTB cases were reported in Shandong in 2015, and the reported incidence rates of active PTB and SS+PTB were 33.09/100 000 and 8.99/100 000, respectively. Active PTB had positive spatial autocorrelation at county level, and the value of Moran's I value was 0.219 (P<0.001), indicating that the high-high (HH) aggregation areas with high incidence were in the northwestern, southeastern and central southern Shandong; SS+PTB also had positive spatial autocorrelation at county level, and the value of the Moran's I was 1.178 (P<0.001), indicating that the HH aggregation areas with high incidence were in the southeastern and northwestern Shandong. The results of spatial temporal scanning indicated that there was incidence clustering of active PTB in the second quarter and the third quarter in 2015, and the clustering areas were in the central southern, southeastern and northwestern Shandong; there also was incidence clustering of SS+PTB in the second quarter and the third quarter in 2015, and the clustering areas were in the southeastern and northwestern Shandong. Conclusions: The incidence of active PTB and SS+PTB showed spatial and temporal clustering in Shandong in 2015. The areas with high PTB burden and high PTB transmission risks were in the northwestern and southeastern Shandong. The areas with high PTB burden but without high PTB transmission risks were in the central southern Shandong. PMID- 27655575 TI - [Survival analysis of HIV/AIDS patients with access to highly antiretroviral therapy in Ningbo during 2004-2015]. AB - Objective: To understand the epidemiology characteristics and survival status of HIV/AIDS patients with access to highly antiretroviral therapy (HAART) in Ningbo during 2004-2015. Methods: A retrospective cohort study was conducted among HIV/AIDS patients diagnosed between 2004 and 2015. Life Tables were used to estimate survival rates, and Kaplan-Meier curve with Log rank test were used to describe the survival curves and the Cox proportional hazard model was used to determine predictors of mortality. Results: Of the subjects, the median age when starting HAART was 35 years (IQR: 27-45 years). Most of them were males, local residents, married, infected through heterosexual sexual transmission, and their baseline CD4 T cells counts were mainly <=200 cells/MUl, and most of them were at clinical stageI(WHO). The cumulative survival rate was 96.75% for the first year, 92.36% for the fifth year, 91.87% for the seventh year and 90.02% for the tenth year. The risk of the mortality was 17.34 times higher for those aged >60 years compared with those aged <=20 years (95%CI: 2.11-142.71), 2.83 times higher for those at clinical stage IV(WHO) compared with those at clinical stageI (WHO) (95% CI: 1.67-4.80) and 3.26 times higher for those with drug resistance compared with those without drug resistance (95%CI: 1.77-6.01). Blood transmission, lower CD4+ T cell level, BMI <18.5, unmarried were the risk factors for the mortality. Conclusions: The effect of HAART was obvious in the HIV/AIDS patients in Ningbo, their survival rate was high. The finding indicated that it is necessary to strengthen the health care for old population and health education about AIDS prevention and control, and conduct large scale screening. Early discovery, early diagnosis, early treatment and improving treatment compliancy are still the effective ways to reduce the mortality. PMID- 27655576 TI - [Probability of premature mortality caused by non-communicable diseases in Beijing, 2010-2015]. AB - Objective: To understand the probability of premature mortality caused by non communicable diseases (NCD) in Beijing from 2010 to 2015. Methods: The data of deaths from Beijing vital registration system were used to analyze age standardized NCD mortality rates, proportion of NCD deaths in age group <70 years and premature NCD mortality. Results: NCD deaths accounted for 90% of the total deaths in Beijing. Age-standardized NCD death rate decreased from 332.43/100 000 in 2010 to 280.02/100 000 in 2015. Meanwhile, the probability of deaths from four NCDs between in age group 30-70 years (premature NCD mortality) decreased from 12.81% to 11.11% in Beijing. The premature mortality of four NCDs in men was 14.63%, and compared with 2015 baseline, it would decrease by 16.4% to reach 2025 goal (12.23%), and the probability of premature mortality four NCDs in women was 7.54%, and compared with 2015 baseline, it would decrease by 6.8% to reach the 2025 goal (7.03%). People living in suburb areas had a higher probability of premature NCD mortality (13.67%) than those living in urban areas (9.72%) in Beijing in 2015. Conclusions: The premature NCD mortality was much higher in men than in women in Beijing. More attention should be paid to the control of risk factors for NCD premature deaths, especially in men and in suburb residents, to reach the 25*25 goal. PMID- 27655577 TI - [Prevalence of loss of activities of daily living and influencing factors in elderly population in China]. AB - Objective: To investigate the prevalence of the loss of basic activities of daily living (ADL) and instrumental ADL (IADL) influencing factors in the elderly population in China and provide evidence for the effective keeping and improvement of the elderly daily living. Methods: The information about demographic characteristics and activities of daily living of elderly Chinese aged >=60 years were collected by using the data of 2013 China Health and Retirement Longitudinal Study. The elderly's ADL of taking bath, eating, getting in and out of bed, dressing, toilet use, and defecating and the IADL of doing housework, cooking, making phone call, taking medicine, shopping and money managing were evaluated. The differences in loss of ADL among different populations were compared by chi2 test and logistic regression analysis was conducted to identify influencing factors for the loss of ADL and IADL. Results: The overall ADL loss rate was 23.8% and the overall IADL loss rate was 35.4% in elderly Chinese. The proportion of having trouble in toilet use was highest among all ADL items, followed by bathing and getting in and out of bed. The proportion of having trouble in making phone call was highest among all IADL items, followed by doing housework and money managing. Female, older age, low educational level, living in central and western China, chronic diseases and disability were factors associated with ADL loss and IADL loss; the divorced or separated, widowed were more likely to have ADL loss; people living in rural area were more likely to have IADL loss. Conclusion: It is necessary to take comprehensive measures to delay and reduce the ADL and IADL loss in elderly Chinese and provide timely and appropriate health care for the elderly with ADL or IADL loss. PMID- 27655579 TI - [Influence of hypertension disorder complicating pregancy and its interaction with other factors on incidence of small for gestational age]. AB - Objective: To understand the influence of hypertension disorder complicating pregancy on the incidence of small for gestational age (SGA) and its interaction with other factors. Methods: A nested case-control study was conducted to analyze the influence of hypertension disorder complicating pregancy on the incidence of small for gestational age and evaluate the interaction between hypertension disorder complicating pregancy and other factors. Results: Data from 6 297 subjects were collected, including 836 (13.28%) pregnant women with hypertension disorder complicating pregancy, 789 (12.53%) infants who were small for gestational age. Compared with the pregnant women without hypertension disorder complicating pregancy, women with hypertension disorder complicating pregancy (aOR=2.185, 95% CI: 1.266-3.770), preeclampsia- eclampsia (aOR=5.322, 95% CI: 4.224-6.707) and with chronic hypertension complicated with superimposed preeclampsia (aOR=3.794, 95% CI: 2.190-6.573) had increased risk for the incidence of small for gestational age. The Interaction analysis showed that there was strong positive interactions between hypertension disorder complicating pregancy and premature birth on small for gestational age infants (RERI=5.260, AP=0.586, SI=2.941), (OR=2.331, 95%CI: 1.443-3.767). Addictive interaction was found between hypertension disorder complicating pregancy and placental abruption (RERI=5.631, AP= 0.522, SI=2.352), and between hypertension disorder complicating pregancy and female fetuses (RERI= 3.660, AP=0.374, SI=1.714), and between hypertension disorder complicating pregancy and oligohydramnios (RERI=10.619, AP=0.636, SI=3.093). However, no significant multiplication interaction was found. Conclusions: Hypertension disorder complicating pregancy is the risk factor of the incidence of small for gestational age. Hypertension disorder complicating pregancy also showed addictive interaction on the incidence of small for gestational age with female fetuses, placental abruption as well as oligohydramnios. There was addictive and multiplication interactions between hypertension disorder complicating pregancy and premature birth. PMID- 27655578 TI - [Analysis on molecular genetic evolution of Banna virus based on the 12th segment]. AB - Objective: To understand the evolution characteristics of Banna viruses (BAVs) isolated worldwide from 1980 to 2012. Methods: In this study, a phylogenetic analysis using Bayesian Markov Chain Monte Carlo simulations was conducted on all available 12th segment of genes of BAVs isolated worldwide from 1980 to 2012 to investigate the evolutionary and epidemiologic dynamics of BAVs. Results: The Bayesian phylogenetic analysis of BAVs revealed that the common ancestor of BAVs appeared 315 (95%HPD: 63-619) years ago. The evolutionary rate of BAV based on the 12th segment gene was estimated to be 2.33*10-3 (95%HPD: 2.84* 10-4-8.52*10 3) substitution per site per year, indicating BAV belong to an emerging arbovirus with rapid evolution. Conclusion: The evolution of emerging BAVs is rapid and the distribution of BAVs has expanded with new variant being detected, so it is necessary to enhance the surveillance to fully understand the natural distribution and pathogenicity of BAVs. PMID- 27655580 TI - [Association between SEC16B polymorphisms and body mass index variation or risk of obesity: a Meta-analysis]. AB - Objective: To systematically evaluate the associations between SEC16B polymorphisms and body mass index (BMI) or risk of obesity in different ethnic populations. Methods: A literature retrieval was carried out by using Wanfangdata, Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP databases), PubMed, Embase, Web of Science, NIH GWAS catalog databases to collect the research papers published between 2009 and 2015 on the associations between SEC16B polymorphisms and BMI or risk of obesity. Summary beta estimates (betas), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength for the BMI analyses and obesity status. Meta-analysis was performed with Stata 12.0 software. Results: Totally 15 papers for rs10913469 and 13 papers for rs543874 were included in this Meta analysis. Under additive genetic model, rs10913469 and rs543874 in SEC16B gene were positively associated with BMI, and the combined beta was 0.04 (95%CI: 0.03 0.05) and 0.03 (95%CI: 0.02-0.04), respectively, and rs10913469 and rs543874 were also associated with the risk of obesity, and the combined OR was 1.11 (95%CI: 1.08-1.15) and 1.28 (95%CI: 1.20-1.36), respectively. There were no significant differences among subgroups of ethnicity, different age groups and literatures with different quality. Conclusion: rs10913469 and rs543874 in SEC16B gene are significantly associated with BMI and the risk of obesity, and C allele of rs10913469 and G allele of rs543874 increase the risk for obesity in different ethnic populations. PMID- 27655581 TI - [The accuracy of mammography screening for breast cancer: a Meta-analysis]. AB - Objective: To estimate the accuracy of mammography for population-based breast cancer screening. Methods: Studies of screening mammography performance were systematically reviewed in the Medline, Embase, Cochrane and China National Knowledge Infrastructure (CNKI) literature databases. The retrieval was performed by using related key words, including disease name, screening and intervention indicators and study type. A total of 1 167 records were retrieved by June 4, 2015 and those studies met the inclusion criteria were included for the current analysis. The numbers of true-positive, false-positive, false-negative and true negative were originally extracted and calculated from each individual study. A QUADAS checklist was used to assess the quality of the studies. A curve of summary receiver operating characteristic (SROC) was applied as a comprehensive assessment of diagnosed accuracy. The pooled effect size of both sensitivity and specificity was quantitatively synthesized in both total population and subgroup with dense breast using the bivariate mixed-effects models. We conducted a sensitivity analysis in the studies with sample size over 100 000. Heterogeneity between studies was measured by the Q test and I2 statistic, and publication bias was evaluated by a funnel plot and the linear regression test. Results: A total of 48 publications with 8 551 873 individuals were identified for the final qualitative synthesis, most of them were from Europe area and American (38 studies), 8 were from Asia area, and 2 were from Oceania area. The studies were conducted during period of 1975-2013, and the age of study women ranged mostly from 40 to 75 years. The area under the SROC curve (AUC) was 0.95 (95%CI: 0.93 0.97). It was estimated that the pooled sensitivity and specificity were 0.81 (95%CI: 0.77-0.84) and 0.96 (95%CI: 0.94-0.96), respectively. The results were indicated stable and robust in sensitivity analysis. In the subgroup with dense breast, the sensitivity and specificity were 0.74 (95% CI: 0.61-0.83) and 0.93 (95% CI: 0.89-0.96), respectively. Funnel plot and test results showed there was no significant publication bias among the included studies. Conclusion: The accuracy of mammography is high for population-based breast cancer screening in women, although the sensitivity is lower in women with dense breast. PMID- 27655582 TI - [Relationship between maternal exposure factors and small for gestational age infant]. AB - Through literature study, this paper summarizes the current status of research on the relationship between maternal exposure factors and small for gestational age infant both in China and abroad. And at the same time, the relationship between pregnancy outcome of small for gestational age and maternal exposure factors was analyzed. This might contribute to reduce the incidence of small for gestational age infant and provide important guidance and references for perinatal care. PMID- 27655583 TI - [Progress in research of health-related quality of life]. AB - Health-related quality of life (HRQoL) is a multidimensional concept for the comprehensive assessment of people's physical and mental health status, which plays an irreplaceable role in clinical treatment, pharmaceutics research, prevention and health care, health policy decision and health economy evaluation, etc. This paper summarizes the connotation, research status, assessment scales and influencing factors of health-related quality of life in order to provide reference to improve the research of health-related quality of life in the future. PMID- 27655584 TI - Cytomegalovirus esophagitis developing during chemoradiotherapy for esophageal cancer: two case reports. AB - BACKGROUND: It is well known that cytomegalovirus esophagitis occurs in immunosuppressed patients. However, few reports have described cytomegalovirus esophagitis occurring during chemoradiotherapy for esophageal cancer. CASE PRESENTATION: We report two cases of patients with cytomegalovirus esophagitis that developed during chemoradiotherapy for esophageal cancer. Cytomegalovirus esophagitis was diagnosed based on the presence of intranuclear inclusions in tumor biopsy specimens. The two Japanese patients presented with anorexia and fever, which improved with anti-cytomegalovirus treatment, and intranuclear inclusions were no longer seen in the specimens. CONCLUSIONS: The possibility of cytomegalovirus esophagitis must be kept in mind for patients with esophageal cancer presenting with prolonged fever or digestive symptoms while receiving chemoradiotherapy. PMID- 27655585 TI - E-Cigarette Policies on College Campuses: Student Use Behaviors, Awareness, and Policy Support. AB - This study examined e-cigarette use and attitudes toward e-cigarette policies among students at colleges and universities with and without policies prohibiting e-cigarette use on campus. In April 2015, we fielded an online survey with a convenience sample of 930 students at 14 North Dakota colleges and universities. The survey included questions about e-cigarette use, observed e-cigarette use on campus, awareness of school e-cigarette policy, and support for policies prohibiting e-cigarette use on campus. Over 40 % of respondents had used e cigarettes at least once, and most current users reported using them rarely (36 %). Nearly 29 % of respondents reported observing e-cigarette use on campus, and more than half of these reported seeing e-cigarette use indoors. More than 42 % did not know whether their school's policy prohibited e-cigarette use on campus, and students at schools with a policy were more likely to identify their campus policy correctly. Sixty-six percent of respondents were in favor of policies prohibiting e-cigarette use on campus, and those at schools with policies prohibiting e-cigarette use were more likely to support a campus e-cigarette policy. Policies prohibiting e-cigarette use on campus intend to restrict use, reduce prevalence, and shape social norms. This study indicates that support for campus e-cigarette policies is high, although awareness of whether e-cigarettes are included in college and university policies is low. These findings demonstrate the need for coordinated policy education efforts and may guide college administrators and student health services personnel as they consider how to implement and evaluate campus e-cigarette policies. PMID- 27655586 TI - Electronic Communication Channel Use and Health Information Source Preferences Among Latinos in Northern Manhattan. AB - Understanding key health concepts is crucial to participation in Precision Medicine initiatives. In order to assess methods to develop and disseminate a curriculum to educate community members in Northern Manhattan about Precision Medicine, clients from a local community-based organization were interviewed during 2014-2015. Health literacy, acculturation, use of Internet, email, and text messaging, and health information sources were assessed. Associations between age and outcomes were evaluated; multivariable analysis used to examine the relationship between participant characteristics and sources of health information. Of 497 interviewed, 29.4 % had inadequate health literacy and 53.6 % had access to the Internet, 43.9 % to email, and 45.3 % to text messaging. Having adequate health literacy was associated with seeking information from a healthcare professional (OR 2.59, 95 % CI 1.54-4.35) and from the Internet (OR 3.15, 95 % CI 1.97-5.04); having <= grade school education (OR 2.61, 95 % CI 1.32 5.17) also preferred information from their provider; persons >45 years (OR 0.29, 95 % CI 0.18-0.47) were less likely to use the Internet for health information and preferred printed media (OR 1.64, 95 % CI 1.07-2.50). Overall, electronic communication channel use was low and varied significantly by age with those <=45 years more likely to utilize electronic channels. Preferred sources of health information also varied by age as well as by health literacy and educational level. This study demonstrates that to effectively communicate key Precision Medicine concepts, curriculum development for Latino community members of Northern Manhattan will require attention to health literacy, language preference and acculturation and incorporate more traditional communication channels for older community members. PMID- 27655587 TI - Relative significances of pH and substrate starch level to roles of Streptococcus bovis S1 in rumen acidosis. AB - To clarify the relative importance of pH and substrate starch level in fermentation characteristics and regulatory mechanism of Streptococcus bovis S1 in rumen acidosis, an in vitro fermentation of three levels of soluble starch (1, 3 and 9 g/L) was established with pH in the media were maintained constant at 5.5 or 6.5. The results showed that the dominant product of S. bovis S1 was lactate at both pH, the production depended on the starch level, and more lactate was produced at pH 6.5 than that at pH 5.5 (P < 0.001). At pH 5.5, the activity of lactate dehydrogenase (LDH) and alpha-amylase (alpha-AMY), their abundances, the relative expressions of LDH, PFL (gene encoding pyruvate formate-lyase), CCPA (gene encoding global catabolite control protein A) and alpha-AMY genes were higher than those at pH 6.5 (P < 0.05), whereas the concentration of fructose-1,6 diphosphate (FDP) was lower. The activity of LDH, alpha-AMY and FDP, and the relative expressions of LDH, PFL, CCPA and alpha-AMY genes were, in general, positively related to the starch level. The canonical regression analysis indicated that the pH had more profound effect compared with the starch level, in terms of the acid productions, enzyme activity and gene expressions. It was concluded that the fermentation of S. bovis was regulated at the transcription level in response to both pH and substrate starch concentration, but more sensitive to pH changes. PMID- 27655589 TI - Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies. AB - BACKGROUND: A striking gender disparity in the incidence and outcome of primary liver cancer (PLC) has been well recognized. Mounting evidence from basic research suggests that hormonal factors may be involved in the gender disparity of PLC. Whether hormonal exposures in human subjects are associated with PLC risk is largely unknown. OBJECTIVE AND RATIONALE: Whether reproductive factors and use of menopausal hormone therapies (MHTs) in women are associated with PLC risk remains controversial. We conducted this study to clarify this issue. SEARCH METHODS: PubMed and EMBASE were searched to July, 2016 for studies published in English or Chinese. Observational studies (cohort, nested case-control and case control) that provided risk estimates of reproductive factors, MHTs and PLC risk were eligible. The quality of included studies was determined based on the Newcastle-Ottawa quality assessment scale. Summary risk ratios (RRs) were calculated using a random-effects model. Dose-response analysis was conducted where possible. OUTCOMES: Fifteen peer-reviewed studies, involving 1795 PLC cases and 2 256 686 women, were included. Overall meta-analyses on parity and PLC risk did not find any significant associations; however, when restricting to studies with PLC cases >=100, increasing parity was found to be significantly associated with a decreased risk of PLC [RR for the highest versus lowest parity 0.67, 95% CI 0.52, 0.88; RR for parous versus nulliparous 0.71, 95% CI 0.53, 0.94; RR per one live birth increase 0.93, 95% CI 0.88, 0.99]. A J-shaped relationship between parity and PLC risk was identified (Pnon-linearity < 0.01). Compared with never users, the pooled RRs of PLC were 0.60 (95% CI 0.37, 0.96) for ever users of MHT, 0.73 (95% CI 0.46, 1.17) for ever users of estrogen-only therapy (ET) and 0.67 (95% CI 0.45, 1.02) for ever users of estrogen-progestin therapy (EPT). The pooled RR of PLC for the oldest versus youngest category of menarcheal age was 0.50 (95% CI 0.32, 0.79). Oophorectomy was significantly associated with an increased risk of PLC (RR 2.23, 95% CI 1.46, 3.41). No significant association of age at first birth, and spontaneous or induced abortion with PLC risk was found. No meta-analysis was performed for the association of age at menopause, breastfeeding, hysterectomy, menopausal status and stillbirth with PLC risk owing to huge methodological heterogeneity and/or very limited studies. WIDER IMPLICATIONS: Parity is associated with PLC risk in a J-shaped dose-response pattern. Late age at menarche and ever use of MHT are associated with a reduced risk of PLC, whereas there is no association of ever use of ET and EPT, age at first birth, or spontaneous and induced abortion with PLC risk. Compared to women with no history of oophorectomy, those with a history of oophorectomy are at an increased risk of PLC. Our findings provide some epidemiological support for a role of hormonal exposures in the development of PLC in women. However, these findings should be interpreted with much caution because of the limited number of studies and potential biases, and need to be validated by studies with good design and large sample size. PMID- 27655591 TI - [Health effect assessment of risk factors for developing population intervention strategies]. AB - Population health is affected by distal factors such as social, economic, cultural factors, proximal factors such as behavior, environment and health services, and biologic factors such as genetics and local microbial populations. Nowadays, China is in the throes of rapid economic and social development, which may affect disease patterns through changes in behavior, environment or communicable disease. This paper addresses the burden of disease attributable to common behavior, environmental and disease risk factors in 2013, and changes in their influence between 1990 and 2013. According to these findings, we can discern critical factors that affecting population health, identify the target populations of public health intervention projects, and design effective and more targeted prevention strategies to control the burden of chronic diseases. PMID- 27655590 TI - Long non-coding RNAs in human early embryonic development and their potential in ART. AB - BACKGROUND: Human long non-coding RNAs (lncRNAs) are an emerging category of transcripts with increasingly documented functional roles during development. LncRNAs and roles during human early embryo development have recently begun to be unravelled. OBJECTIVE AND RATIONALE: This review summarizes the most recent knowledge on lncRNAs and focuses on their expression patterns and role during early human embryo development and in pluripotent stem cells (PSCs). Public mRNA sequencing (mRNA-seq) data were used to illustrate these expression signatures. SEARCH METHODS: The PubMed and EMBASE databases were first interrogated using specific terms, such as 'lncRNAs', to get an extensive overview on lncRNAs up to February 2016, and then using 'human lncRNAs' and 'embryo', 'development', or 'PSCs' to focus on lncRNAs involved in human embryo development or in PSC.Recently published RNA-seq data from human oocytes and pre-implantation embryos (including single-cell data), PSC and a panel of normal and malignant adult tissues were used to describe the specific expression patterns of some lncRNAs in early human embryos. OUTCOMES: The existence and the crucial role of lncRNAs in many important biological phenomena in each branch of the life tree are now well documented. The number of identified lncRNAs is rapidly increasing and has already outnumbered that of protein-coding genes. Unlike small non-coding RNAs, a variety of mechanisms of action have been proposed for lncRNAs. The functional role of lncRNAs has been demonstrated in many biological and developmental processes, including cell pluripotency induction, X-inactivation or gene imprinting. Analysis of RNA-seq data highlights that lncRNA abundance changes significantly during human early embryonic development. This suggests that lncRNAs could represent candidate biomarkers for developing non-invasive tests for oocyte or embryo quality. Finally, some of these lncRNAs are also expressed in human cancer tissues, suggesting that reactivation of an embryonic lncRNA program may contribute to human malignancies. WIDER IMPLICATIONS: LncRNAs are emerging potential key players in gene expression regulation. Analysis of RNA seq data from human pre-implantation embryos identified lncRNA signatures that are specific to this critical step. We anticipate that further studies will show that these new transcripts are major regulators of embryo development. These findings might also be used to develop new tests/treatments for improving the pregnancy success rate in IVF procedures or for regenerative medicine applications involving PSC. PMID- 27655592 TI - [Recognition of the vaccination: a key and important strategy in controlling vaccine preventable diseases]. AB - China has achieved an outstanding accomplishment in combating infectious diseases, which has contributed to health improvement and prolongation of life expectancy, and health development globally. Among strategies for combating infectious diseases, vaccination is a key component. However, immunization rates have fallen sharply as a result of false information, inconvenient access to vaccination, and distrust which together can lead to "vaccine hesitancy", eventually resulting in the risk of endemic vaccine-preventable disease. By analyzing the importance of vaccination and its determinants, it should be recognized that vaccination is necessary to protect children's health, and considered as a key national policy with forceful strategies for the control of vaccine-preventable diseases. PMID- 27655593 TI - [Burden of disease attributable to high- sodium diets in China, 2013]. AB - Objective: To examine the burden of disease(BOD)attributable to high-sodium diets in China in 2013. Methods: Data were extracted from the 2013 Global Burden of Disease Study for China to examine the BOD attributable to high-sodium diets in 2013, gender, and disease composition. Measurements for attributable BOD were population attributable fraction(PAF), deaths, standardized mortality and disability-adjusted life years(DALY)(not including Taiwan, China). An average world population age-structure for the period 2000-2025 was adopted to calculate age-standardized rates. Results: In 2013, deaths attributable to high-sodium diets accounted for 12.6% of all deaths and 14.5% of chronic disease deaths. Overall, 7.8% of deaths because of neoplasms, 25.2% of cardiovascular disease deaths, and 22.9% of chronic kidney disease deaths were attributable to high sodium diets. A total of 1 176 553 deaths were attributable to high-sodium diets and the standardized mortality was 91.5/100 000, which was higher in men than in women(121.7/100 000 and 63.0/100 000, respectively). Overall, 22.759 million DALYs were attributable to high-sodium diets. The DALY standardized rate was 1 588.0/100 000, which was higher in men than in women(2 189.7/100 000 and 993.2/100 000, respectively). When compared by province, PAF in Xinjiang(25.0%), Qinghai(23.7%), Shanxi(23.2%), Tibet(22.1%)and Shandong(20.5%)was higher than other provinces. The standardized mortality in Xinjiang(239.4/100 000), Qinghai(238.9/100 000), Tibet(221.7/100 000), Shanxi(166.2/100 000)and Hebei(149.9/100 000)were higher than other provinces. The DALY standardized rate attributable to high-sodium diets was highest in Xinjiang(4 430.8/100 000), Qinghai(4 422.5/100 000), Tibet(4 021.4/100 000), Shanxi(2 816.6/100 000), and Hebei(2 624.9/100 000). Conclusion: The BOD attributable to high-sodium diets is a serious issue in China, particularly in men and in the northern provinces. Effective measures should be taken in northern provinces to reduce sodium intake. PMID- 27655594 TI - [Burden of disease attributed to high total cholesterol in 2013 in China]. AB - Objective: To analyze the burden of disease attributed to high total cholesterol(TC)in 2013 in China. Methods: We used data from the 2013 Global Burden of Disease Study. The population attributable fraction was calculated to estimate the deaths and disability-adjusted life years(DALY)attributed to high TC. Disease burden was compared by age, gender, diseases and province(not including Taiwan, China). An average world population age structure for the period 2000- 2025 was adopted to calculate age-standardized rates. Results: In 2013, high TC caused 298 952 deaths in China, accounting for 3.3% of total deaths, and caused 6 332 thousand DALYs. DALYs attributed to high TC were highest among the 50-69 years age group(3 165 thousand person years), accounting for 50.0% of the total attributed DALYs. The DALY rate in the >=70 years age group was 2 053.3/100 000, which was 10.3 times that of 15-49 age group(198.6/100 000). DALYs among men were 4 431 thousand person years, which was 2.3 times higher than in women(1 900 thousand person years), and the age-standardized DALY rate among men was 590.6/100 000, which was 2.3 times higher than in women(257.1/100 000). DALYs attributed to high TC were mainly caused by ischemic heart disease(IHD; 5 572 thousand person years), accounting for 88.0% of the total attributed DALYs. Deaths and DALYs attributed to high TC were highest in Shandong(31 002 and 628 thousand person years for deaths and DALYs, respectively), Henan(27 398 deaths and 587 thousand person years, respectively), Hebei(25 744 deaths and 589 thousand person years, respectively), accounting for 28.1% of total attributed deaths and 28.5% of total attributed DALYs. The number of deaths and DALY were lowest in Macao(75 deaths and 1 thousand person years, respectively)and Tibet(385 deaths and 10 thousand person years, respectively). The age standardized DALY rates were highest in Beijing(794.8/100 000), Hebei(732.7/100 000), and Jilin(709.1/100 000), and lowest in Shanghai(151.4/100 000), Zhejiang(168.1/100 000), and Hong Kong(182.0/100 000). Conclusion: The burden of disease attributed to high TC in 2013 in China was mainly the result of the IHD it causes, with greater influence among males and those aged >=50 years, and variation among provinces. PMID- 27655595 TI - [Burden of disease attributable to high fasting plasma glucose in 1990 and 2013 in China]. AB - Objective: To analyze the burden of disease attributed to high fasting plasma glucose(FPG)in China in 1990 and 2013. Methods: The analysis used data obtained from the 2013 Global Burden of Diseases Study and examined deaths, death rate, disability-adjusted life years(DALY), years lived with disability(YLD)and years of life lost(YLL)attributed to high FPG in 1990 and 2013 in China(not including Taiwan, China). An average world population age-structure for the period 2000- 2025 was adopted to calculate age-standardized rates. Results: In 2013, the number of deaths attributed to high FPG in China increased to 621.9 thousand from 320.3 thousand in 1990. From 1990- 2013, the age-standardized death rate attributable to high FPG increased from 45.69/100 000 to 48.64/100 000. DALYs caused by high FPG increased to 20.389 1 million in 2013 from 10.648 3 million in 1990. In 2013, high FPG caused 8.751 5 million YLD and 11.637 6 million YLL, and the percentage of YLL in DALY decreased to 57.1% in 2013 from 68.7% in 1990. Compared with 1990, the age-standardized DALY rate attributed to high FPG increased by 10.81%. In 2013, the top three provinces with the highest burden of disease attributed to high FPG were Xinjiang, Jilin and Liaoning provinces, with standardized death rates of 83.38, 74.01 and 68.64/100 000, respectively, and the standardized DALY rate was 2 217.96, 2 001.84 and 1 837.79/100 000 in the three provinces, respectively. Conclusion: Compared with 1990, the burden of disease attributed to high FPG in 2013 increased substantially in China, in particular the burden of attributed YLD. However, the burden of YLL attributed to high FPG has decreased modestly. The burden of disease caused by high FPG shows variation among different provinces in China. PMID- 27655588 TI - The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis. AB - BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field. PMID- 27655596 TI - [Mortality attributable to high body mass index in Chinese people aged 15 or over, in 1990 and 2013]. AB - Objective: To analyze and compare deaths(mortality)attributable to high body mass index(BMI)in Chinese population aged >=15 years between 1990 and 2013. Methods: We used the results of the 2013 Global Burden of Disease Study for China, based on population attributable fractions(PAF)to analyze deaths attributable to high BMI in all provinces(not including Taiwan, China)in 1990 and 2013. The average world population from 2000 to 2025 was used as a reference to calculate age standardized mortality rates, and to compare the change of attributable deaths in 1990 and 2013. Results: In 2013, the number of deaths attributable to high BMI was 640 294, compared with 301 231 in 1990, an increase of 114.27%. Compared with 1990, in 2013, the number of deaths and age-standardized mortality rate attributable to high BMI showed a higher growth rate in men(142.81% and 30.74%, respectively)than women(84.69% and 2.88% , respectively). The growth rate of attributable deaths increased with age. Compared with 1990, in 2013, the growth rates of attributable deaths among 15-49, 50-69 and >=70 years age groups were 63.37%, 89.11% and 183.64%, respectively. In both 1990 and 2013, the top three diseases in terms of deaths attributable to high BMI were stroke(128 657 and 247 042, respectively), ischemic heart disease(57 173 and 156 614, respectively), and hypertensive heart disease(34 960 and 58 435, respectively). Compared with 1990, in 2013, the standardized mortality rates of chronic kidney disease(129.44%), pancreatic cancer(101.76%), colorectal cancer(85.45%)and breast cancer(63.86%)showed more substantial increases. In 1990, the top three provinces with most deaths attributable to high BMI were Henan(31 376), Shandong(27 969)and Hebei(24 164), while in 2013 they were Shandong(61 897), Hebei(58 383)and Henan(57 501). Compared with 1990, in 2013, the age-standardized mortality rate attributable to high BMI increased in 26 of 33 provinces, with a faster increase in Qinghai(56.96%), Guizhou(45.30%)and Yunnan(39.39%). The rate declined in the other seven provinces, declining faster in Tianjin(20.68%), Macao(14.08%)and Jilin(6.86%). Conclusion: Deaths and age-standardized mortality rates attributable to high BMI increased rapidly between 1990 and 2013, with higher increases in men than in women. Age-standardized mortality rates of chronic kidney disease, pancreatic cancer, colorectal cancer and breast cancer attributable to high BMI showed much higher growth rates than other attributed diseases. The highest BMI-attributed age-standardized mortality rates were found in northeast and northern provinces, and the fastest growth rates of BMI attributed age-standardized mortality rates were observed in southwest and northwest provinces. PMID- 27655597 TI - [The burden of disease attributed to low bone mineral density among population aged >=40 years old in China, 1990 and 2013]. AB - Objective: To identify cause-specific death and attributed burden of low bone mineral density in China among population aged >=40 years old , 1990 and 2013. Methods: By using data from Global Burden of Disease(GBD)2013, this study analyzed death caused by low mineral density, and disability-adjusted life years(DALY)among population aged 40 and above in China(not including Taiwan, China). This study also analyzed DALY by composition of injury which due to low bone mineral density. It also analyzed changes in DALY by provinces in China, 1990 and 2013. An average world population age-structure for the period 2000- 2025 was adopted to calculate the age standardized rates. Results: In 2013, there were 38.1 thousands male and 30.7 thousands female who aged 40 and above dead due to low bone mineral density in China. The burden of injury caused by low bone mineral density was more sever in male than female, which accounted for 1.525 million DALY in male and 0.873 million DALY in female. In 1990, low bone mineral density attributed transportation and accidental injury caused 0.794 million and 0.567 million DALY losses, respectively. In 2013, low bone mineral density attributed transportation and accidental injury caused 1.421 million and 0.951 million DALY losses, respectively. Compared to 1990, DALY losses caused by transportation and accidental injury, increased by 79.1% and 67.6%, respectively. In 1990, DALY rate losses due to low bone mineral density attributed transportation and accidental injury were 68.1 per 100 000 and 48.7 per 100 000, respectively. In 2013, DALY rate losses due to low bone mineral density attributed transportation and accidental injury were 102.0 per 100 000 and 68.2 per 100 000, respectively. Compared to 1990, DALY rates which caused by transportation and accidental injury, increased by 49.8% and 40.2%, respectively. According to the ranking of standardized DALY rate in 2013 by provinces, the top 3 provinces, which standardized DALYs attributed to low bone mineral density lost the most, were Zhejiang Province(2.6 per 100 000), Jiangsu Province(2.4 per 100 000), and Fujian Province(2.2 per 100 000). Compared to 1990, the standardized rate of DALY decreased in 27 provinces, while the DALY rate increased in only 6 provinces which included Ningxia Hui Autonomous Region, Qinghai Province, Hebei Province, Guangxi Zhuang Autonomous Region, and Henan Province and Xinjiang Uygur Autonomous Region. Conclusion: This study found that the burden of health losses attributed to it was higher in men than in women. Compared to 1990, DALY rates decreased in most of the provinces, however, the rates of losses of DALY which caused by transportation and accidental injury were still increasing. PMID- 27655598 TI - [Proton nuclear magnetic resonance spectroscopy recognition of metabolic patterns in fecal extracts for early diagnosis of colorectal cancer]. AB - Objective: To characterize the metabolic " fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer(CRC)using proton nuclear magnetic resonance spectroscopy(1H-NMR)-based metabolomics coupled with pattern recognition. Methods: From January 2014 to December 2014, we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College, from 25 patients with colorectal adenomas(CR-Ad), 20 with stage I/II CRC, and 32 healthy controls(HCs). The patients were diagnosed by histopathology. No subjects had any complicating diseases. HCs showed no abnormalities from blood tests, endoscopic examination, diagnostic imaging, and/or medical interviews. We excluded participants who used antibiotics, NSAIDS, statins, or probiotics within two months of study participation, and any patients who underwent chemotherapy or radiation treatments prior to surgery. We used orthogonal partial least-squares discriminant analysis(OPLS-DA)for pattern recognition(dimension reduction)on 1H NMR processed data(1H frequency of 400.13 MHz), to find metabolic differences among CR-Ad, carcinoma and HC fecal samples; and receiver operating characteristic(ROC)analysis to determine the diagnostic value of the fecal metabolic biomarkers. Results: Fecal samples were collected from 20 patients with Stage I/II CRC(11 M, 9 F, median age(52+/-13)years), 25 with CR-Ad(14 M, 11 F, median age(53 +/- 11)years)and 32 HCs(15 M, 17 F, median age(53 +/- 14)years). OPLS-DA clearly distinguished CR-Ad and stage I/II CRC from HC samples, based on their metabolomic profiles. Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate(HC: 23.0+/-6.0; CR-Ad: 18.0+/-5.0; CRC: 14.0+/-6.0; Z=-2.07, P=0.008), acetate(HC: 45.0+/-11.0; CR-Ad: 31.0+/-11.0; CRC: 24.0+/-8.0; Z=- 2.32, P=0.011), propionate(HC: 26.0 +/- 7.0; CR-Ad: 22.0 +/- 6.0; CRC: 19.0 +/- 5.0; Z=- 2.43, P=0.032), glucose(HC: 37.0+/-7.0; CR-Ad: 31.0+/ 7.0; CRC: 26.0+/-8.0; Z=-2.07, P=0.044)and glutamine(HC: 4.5+/-2.0; CR-Ad: 4.9 +/ 1.0; CRC: 5.4 +/- 1.0; Z=2.21, P=0.044). However, relative signal intensities in HCs were significantly higher than in patients for lactate(HC: 4.8+/-1.0; CR-Ad: 6.9+/-2.0; CRC: 4.8+/- 1.0; Z=2.02, P= 0.038), glutamate(HC: 3.2 +/- 2.0; CR-Ad: 4.9 +/- 1.0; CRC: 3.2 +/- 2.0; Z=2.21, P=0.044)and succinate(HC: 12.0+/-2.0; CR Ad: 15.0+/-3.0; CRC: 12.0+/- 2.0; Z=2.25, P=0.011). Among the potential biomarkers, acetate at 1.92 ppm, and succinate at 2.41 ppm displayed relatively high area under ROC, with sensitivity and specificity both >90%, to distinguish early-stage CRC patients from HCs. Conclusion: Fecal metabolic profiles distinguish of HCs from patients with CRC patients, even in the early stages(stage I/II), highlighting the potential of NMR-based fecal metabolomic fingerprinting as tools for early CRC diagnosis. PMID- 27655599 TI - [The combined effects of family history of cardiovascular disease and overweight on ischemic stroke incidence among the Mongolian population]. AB - Objective: To investigate the cumulative effect of family history of cardiovascular disease(CVD)and overweight on ischemic stroke events in the Mongolian population. Methods: Study participants were recruited from 32 villages from May 2002 to August 2012 in Kezuohou Banner(county)and Naiman Banner in Inner Mongolia, China. Among 3 457 Mongolian people aged >=20 years old living in these villages, 2 589 were selected to participate in this study. None of the participants had chronic kidney disease, malignant tumor, thyroid disease or adrenalopathy, or acute infectious disease. The 2 589 participants were followed for a mean of 9.2 years. Six participants were lost to follow up, resulting in a follow-up rate of 99.8%. Information collected included demographic characteristics, lifestyle risk factors, alcohol consumption, cigarette smoking, history of disease, family history of CVD, and physical examination. Ischemic stroke incidence information was collected during follow-up. All participants were categorized into four subgroups according to family history of CVD and overweight status. Cox proportional hazards models were used to estimate the hazard ratios(HR)and 95% CI of ischemic stroke events among subgroups, compared with the subgroup with no family history of CVD and body mass index(BMI)<24 kg/m2(the reference group). Results: Among 2 589 participants, 76 ischemic stroke events occurred after follow-up, and 8 were excluded because of lack of key data. Finally, 2 581 participants were included in the analysis, and the incidence density was 323/100 000 person-years. The cumulative incidence rates of ischemic stroke were 2.48%, 1.86%, 6.67% and 9.00% in the no family history of CVD and BMI <24 kg/m2, no family history of CVD and BMI >=24 kg/m2, family history of CVD and BMI <24 kg/m2 and family history of CVD and BMI >= 24 kg/m2 subgroups, respectively. Using the Cox proportional hazards model, after further adjustment for age, gender, smoking, drinking, FPG, hypertension, total cholesterol, triglycerides, and heart rate, the risk of ischemic stroke in the subgroup with a family history of CVD and BMI >=24 kg/m2 was higher than the reference group(HR: 2.61, 95% CI: 1.16-5.87). However, the risk of ischemic stroke in other two groups was not statistically significant compared with the reference group. The HR(95% CI)values in the no family history of CVD and BMI >=24 kg/m2and family history of CVD and BMI <24 kg/m2 subgroups were 1.18(0.5- 2.39)and 1.27(0.67- 2.42), respectively. Conclusion: In the Mongolian population, a family history of CVD and coexistent overweight may increase the risk of ischemic stroke events, suggesting that in people with family history of cardiovascular disease, weight control is conducive to the prevention of ischemic stroke. PMID- 27655600 TI - [Prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China]. AB - Objective: The purpose of this study was to investigate the prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China. Methods: A total of 20 194 participants aged >=18 years were selected randomly by cluster sampling from two townships(towns)in Henan Province from July to August 2007 and July to August 2008. Investigations included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination at baseline. A total of 16 155 participants were followed up from July to August 2013 and July to October 2014. Overall, 13 869 participants were included in the study, after excluding 2 286 participants with incomplete dyslipidemia follow-up data. Distributions of the characteristics of dyslipidemia were determined, and prevalence was standardized by age according to data of the 2010 Sixth National Population Census. Risk factors for dyslipidemia were analyzed using a logistic regression model after adjusting for sex, age, education level, marital status, and income status. Results: The prevalence of dyslipidemia was 53.72%(7 450/13 869)for residents aged >=22 years living in rural areas of Henan Province(59.32%(3 069/5 174)for men and 50.39%(4 381/8 695)for women). The adjusted prevalence of dyslipidemia was 50.50%(59.27% for men and 45.53% for women). The prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C, and high LDL-C was 4.34%(602/13 868), 20.42%(2 826/13 837), 42.75%(5 927/13 865), and 3.14%(420/13 375), respectively, and the adjusted prevalence was 2.44%, 18.84%, 41.42%, and 1.86%, respectively. Logistic regression analyses showed that alcohol consumption(OR=1.27, 95% CI: 1.05-1.53), family history of hyperlipidemia(OR=1.29, 95% CI: 1.17-1.43), overweight(OR=1.40, 95% CI: 1.22 1.61), obesity(OR= 1.65, 95% CI: 1.39- 1.96), abnormal waist circumference(OR=1.22, 95% CI: 1.04- 1.43), and abnormal waist-height ratio(OR=1.21, 95% CI: 1.01-1.45)were significant independent risk factors, and high levels of physical activity(OR=0.85, 95% CI: 0.77- 0.95)and underweight(OR=0.52, 95% CI: 0.36- 0.75)were protective factors for dyslipidemia after adjusting for sex, age, education level, marital status, and income status. Conclusion: The prevalence of dyslipidemia was very high for this rural population. Alcohol consumption, family history of hyperlipidemia, overweight, obesity, abnormal waist circumference, and abnormal waist-height ratio were significant independent risk factors for dyslipidemia. PMID- 27655602 TI - [Etiological monitoring and analysis of cases of acute flaccid paralysis in Hebei Province in 2011-2014]. AB - Objective: To identify poliomyelitis(polio)virus, the VP1 gene, and its nucleotide sequence in fecal samples from patients with acute flaccid paralysis(AFP)in Hebei Province in 2011-2014. Methods: A surveillance system for AFP was established in Hebei Province in 2011-2014 and registered in 2014. Stool samples, each weighing 5 g, were collected from 1 504, 15-year-old symptomatic patients with AFP, resulting in a total of 3 001 samples(1 497 patients provided duplicate samples and 7 provided single specimens). Poliovirus nucleic acid was extracted, the RNA was reverse transcribed, and a VP1 gene fragment was amplified with real-time PCR. The PCR products were sequenced to construct a phylogenetic tree and check the relatedness of the strains to the Sabin vaccine strain. A chi2 test was used to compare the differences in the incidence of infection in different years. Results: Poliovirus was isolated from 50(1.7%)of the 3 001 stool samples, 10 of which were type I strains, 15 were type II strains, 16 were type III strains, and 9 were mixed-type strains. The positive rates for poliovirus in the years 2011-2014 were 1.0%(9/890), 1.5%(12/824), 2.2%(17/770), and 2.3%(12/517), respectively(chi2=2.24, P=0.525). Analyses of the VP1 nucleotide and amino acid sequence homologies revealed that the type I, type II, and type III poliovirus strains shared nucleotide sequence homologies with the Sabin vaccine strain of 98.8%- 100%, 99.1%- 100%, and 99.2%- 100%, respectively, and amino acid sequence homologies of 98.6%- 100%, 98.3%-100% and 98.6%-100%, respectively. A VP1-based phylogenetic analysis showed that the variation rates for the poliovirus type I, type II, and type III strains were 0.66%, 0.66%, and 0.55%, respectively. Conclusion: Only one poliovirus strain was detected in Hebei Province in 2011-2014, except for the type II vaccine-derived poliovirus. The remaining strains were all similar to the Sabin vaccine strain, with high VP1 homology. PMID- 27655601 TI - [Understanding the risk factors for infectious diseases, their prevention, and control, among residents of Zhejiang Province]. AB - Objective: To investigate the understanding of infectious diseases, their prevention, and control, and the factors influencing this literacy among urban and rural residents of Zhejiang Province. Methods: In November- December 2014, a multistage stratified cluster sampling questionnaire was administered at study sites in eight districts of Zhejiang province: Hangzhou city Gongshu district, Hangzhou city Chun'an county, Wenzhou city Cangnan county, Dongyang city, Jiaxing city Jiashan county, Zhoushan city Putuo district, Linhai city, Lishui city Jinyun county. The inclusion criteria were: 15-60 years old, living locally for more than six continuous months, and no mental illness. The exclusion criteria were: foreigner residing locally, resident of Hong Kong, Macau, or Taiwan, or unable to communicate through speech or writing. In this study, 4 091 questionnaires were distributed, and 4 020 valid questionnaires were returned(98.26%). Health literacy regarding infectious diseases was measured at five levels: knowledge, skills, behaviors, access to information, and understanding of the prevention of infectious diseases. A total score was calculated for each questionnaire, and a total score of >=80 was deemed to indicate an understanding of the prevention of infectious diseases. A chi2 test was used to compare the levels of health literacy in different populations with single-factor analyses, and a multivariate unconditional logistic regression model was used to analyze the factors affecting infectious diseases prevention and treatment literacy levels. Results: Of the 4 020 respondents(aged(43.84 +/- 10.28)years), 1 964 were male(48.86%)and 2 056 were female(51.14%). In the total surveyed population, 15.17%(n=610)understood the prevention of infectious diseases, 294 were male(14.97%)and 316 were female(15.37%)(chi2=2.48, P=0.115). When the participants in the different age groups were analyzed, 23.11%, 20.29%, 13.27%, and 11.04% of those aged 18- 29(n=116), 30- 39(n= 166), 40- 49(n=178), and >=50 years(n=150), respectively, understood infectious disease prevention(chi2= 63.16, P<0.001). When the participants were analyzed according to education, 46.01%, 24.86%, 12.03%, 5.27%, or 2.39% of those educated at university(n=167), at high school/vocational school/college(n=175), at middle school(n=215), at elementary school(n=46), or who were illiterate/slightly literate(n=7), respectively, understood infectious disease prevention(chi2=436.67, P<0.001). Among the urban(n=336)and rural participants(n=274), 18.98% and 12.18% understood infectious disease prevention, respectively(chi2= 35.57, P<0.001), so the urban residents had better health literacy than rural residents(OR=1.28, 95% CI= 1.06- 1.54), and those aged 18- 29 or 30- 39 years had even better health literacy than the rural residents(OR=1.39, 95%CI=1.01-1.91). When the health literacy levels of migrant workers were compared with those of agency/institutional personnel, business people, unemployed, and retirees, the OR(95% CI)values were 2.52(1.82-3.49), 1.69(1.24 2.30), 2.99(1.65-5.39), and 2.43(1.59-3.72), respectively. When the illiterate/slightly literate were compared with those educated at university, high school/vocational school/secondary school, and junior high school, the OR(95%CI)values were 35.11(15.73-78.36), 13.31(6.11-28.99), and 5.37(2.48-11.62), respectively. Conclusion: Limited levels of health literacy are common among the residents of Zhejiang Province. Lower education level, older age, and rural residence were predictors of low health literacy in this study. PMID- 27655603 TI - [Epidemiological characteristics and vertification analysis for acute hepatitis B in Beijing, 2005-2014]. AB - Objective: To analyze epidemiological characteristics of acute hepatitis B(aHPB)in Beijing and to recheck epidemiology and laboratory results of aHPB cases in the sampling area. Methods: We analyzed epidemiological characteristics of aHPB cases reported in National Notifiable Disease Reporting System(NNDRS)from 2005 to 2014 in Beijing, using a stratified cluster sampling method and based on the average reported incidence of hepatitis B from 2005 to 2011 in NNDRS, we projected 430 aHPB cases in the sampling area from 2012 to 2014, for which 307 received blood sample retesting. Inclusion criteria of aHPB cases were those living in Beijing more than 1 year, using name, sex, age, or identity card number as key fields to verify that they had not been previously reported in the database. Accuracy and adjusted aHPB incidence rate for 2005- 2014 in Beijing was analyzed by rechecking aHPB cases. Results: Epidemiological survey showed that aHPB coincidence rate was 89.5%(385/430)in NNDRS from 2012 to 2014 in Beijing. Laboratory tests showed that the aHPB coincidence rate was 92.2%(283/307). The total coincidence rate was 82.54%. The aHPB adjustment incidence rate dropped from 5.05/100 thousand in 2005 to 0.98/100 thousand in 2014 in Beijing. The aHPB adjustment incidence rate among residents younger than 15 years dropped to 0/100 thousand. Conclusion: The incidence of aHPB in Beijing dropped to a low level from 2005 to 2014. There were no aHPB cases in residents younger than 15 years. PMID- 27655605 TI - [Epidemiological analysis on serogroup Y neisseria meningitidis firstly isolated from patient in Tianjin]. PMID- 27655604 TI - [Factors related to syphilis and other infections among female drug users in Shandong women's compulsory drug rehabilitation center in 2015]. AB - Objective: To analyze the prevalence of HIV, syphilis and related factors among female drug users in Shandong women's compulsory drug rehabilitation center(SWCDRC). Methods: During May 2015, we used a cluster sampling method for drug users in SWCDRC, with a questionnaire and serological testing. We included respondents who volunteered to take part in this study, had clear histories of drug abuse, and had no symptoms of psychosis or current drug use; 451 women participated. The questionnaire addressed socio-demographic information and the participants' health knowledge, including AIDS knowledge, behavioral information, drug use, and STD treatment. We also drew 5 ml blood from each subject for serological tests of HIV and syphilis. Chi-square test was used to compare syphilis antibody positive rate among drug users who had different characteristics. Multi-factor unconditioned logistic regression model was used to explore related factors about syphilis infection of women drug users. Results: Subjects' mean age was(27.25+/-7.06)years. Of the 451 women, 33.5%(151/451)tested positive for syphilis and 2.2%(10/451)for HIV. The rate of syphilis antibody(SAb)positive whether providing commercial server, providing: 47.2%(25/53); no providing: 31.6%(125/396); chi2=5.12, P=0.024. The SAb + rate from whether having temporary sexual behavior, having: 47.4%(91/192); no having: 23.6%(60/254); chi2=27.6, P<0.001. The SAb+ rate of subjects who tested positive for herpes simplex virus-2(HSV-2)was 39.4%(128/325); for those who tested negative it was 18.3%(23/126); chi2=18.2, P<0.001. The SAb+ rate by frequency of drug use was >=3 times a week: 36.9%(106/287);<3 times per week: 27.3%(42/154); chi2=4.20, P=0.041. Compared with subjects who were unmarried, divorced, or widowed drug users, the OR(95% CI)for SAb+ among subjects who cohabited with a partner was 2.19(1.36- 3.51). Compared with subjects who had not been having temporary sexual behavior, the OR(95%CI)for SAb+ among subjects who had been having temporary sexual behavior was 2.59(1.65-4.05). Compared with HSV-2- subjects, the OR(95%CI)for SAb+ among subjects who were HSV-2+ was 2.69(1.57 4.59). Conclusion: HIV and syphilis infection rate among female drug users in SWCDRC were significantly higher than in the general population. Subjects who had provided commercial server in the previous 12 months, had temporary sexual behavior in the previous 12 months, were HSV-2+, used drugs >=3 times per week or cohabitated with a partner had higher syphilis prevalence. PMID- 27655606 TI - [Analysis on the characteristics of violence from injury surveillance hospitals in Jiangsu Province, 2006- 2014]. PMID- 27655607 TI - [Evaluation of economic burden of varicella and cost benefit of different immunization strategies of varicella vaccine in Beijing]. PMID- 27655608 TI - [Antimicrobial resistance analysis of salmonella from broiler cultivation and processing production in Heilongjiang Province]. PMID- 27655609 TI - [Research progress of risk assessment model of type 2 diabetes mellitus]. AB - Established models of type 2 diabetes mellitus(T2DM)are used to determine predictors with the aim of disease prevention. Established models are used to determine predictors, then assign risk scores or calculate the probability of T2DM development within a certain timeframe. A number of countries and regions have established T2DM risk assessment models, which can be divided into non invasive and invasive tools, depending on whether they use routinely collected information or laboratory markers. Here, we review the latest progress of two assessment models at the national and international levels, and explore and summarize their applications. The noninvasive Finnish Diabetes Risk Score and the invasive Framingham model are widely used internationally. However, invasive models were more widely applied, as studies on T2DM risk assessment models started relatively late in China. PMID- 27655610 TI - Radiographic evaluation of posterior selective thoracolumbar or lumbar fusion for moderate Lenke 5C curves. AB - INTRODUCTION: Posterior selective thoracolumbar or lumbar (TL/L) fusion with pedicle screw constructs for adolescent idiopathic scoliosis (AIS) has been studied in a few researches. However, few studies have discussed the indication for selective TL/L fusion and the behaviors of its adjacent disc angle. The present study aims to discuss the indication for posterior selective TL/L fusion and the behavior of the adjacent disc angle. METHODS: 45 consecutive cases of AIS undergoing posterior selective TL/L fusion were retrospectively evaluated, with an average follow-up of 36 months. Radiographs were reviewed to determine the coronal curve magnitude and the sagittal alignment preoperatively, postoperatively and at final follow-up. Thoracic curves in groups A had a correction loss of more than 5 degrees , while thoracic curves in group B had a correction loss of not more than 5 degrees . RESULTS: The coronal curve magnitude of the TL/L curve averaged 44 degrees preoperatively and it was corrected to 6 degrees immediately with a correction rate of 84.8 %. At final follow-up it was 9 degrees with a correction loss of 3 degrees . The minor thoracic curve was 26 degrees preoperatively, and the convex side bending curve magnitude averaged 8 degrees with a flexibility of 72.7 %. It was corrected to 13 degrees immediately with a spontaneous correction of 48.5 %. At final follow-up it was 14 degrees with a correction loss of 1 degrees . UIVA decreased from 4 degrees to 2 degrees after surgery, and it was 2 degrees at final follow-up. LIVA decreased from 7 degrees to 4 degrees after surgery, and it was 5 degrees at final follow-up. Maximal correction of TL/L curves in group A is significantly less than that in group B. 1 patient received revision surgery to fuse the progressive thoracic curve. CONCLUSION: Posterior selective TL/L fusion with pedicle screw constructs allows for spontaneous thoracic correction and maintains coronal and sagittal balance during the follow-up. Maximal correction instead of undercorrection was recommended for moderate Lenke 5C curves. Disc wedging could be improved after surgery and well maintained during the follow-up. PMID- 27655611 TI - Evaluation of a Brain Acetylcholinesterase Extraction Method and Kinetic Constants after Methyl-Paraoxon Inhibition in Three Brazilian Fish Species. AB - Acetylcholinesterase (AChE) is an important enzyme in the control of the neuronal action potential and sensitive to organophosphate inhibition. Brain fish AChE is less sensitive to organophosphate inhibition than AChE from terrestrial animals, although this sensitivity is variable among species and has not yet been fully evaluated in fish species. In this setting, inhibition kinetic constants for progressive irreversible inhibition of brain acetylcholinesterase due to methyl paraoxon exposure were determined in three fish species (Mugil liza, Genidens genidens and Lagocephalus laevigatus) and hen (Gallus domesticus). Enzyme extraction using a detergent was shown to be adequate, and samples presented activity inhibition in high substrate concentrations and suppression of inhibition by methyl-paraoxon in the presence of the substrate, similar to kinetic patterns from purified enzyme preparations. Catfish (G. genidens) AChE presented the highest sensitivity among the evaluated fish species (IC50 = 1031.20 nM +/- 63.17) in comparison to M. liza and L. laevigatus (IC50: 2878.83 +/- 421.94 and 2842.5 +/- 144.63 nM respectively). The lower dissociation constant (Kd = 20.3 +/- 2.95 MUM) of catfish AChE showed greater enzyme affinity for methyl-paraoxon, explaining this species higher sensitivity to organophosphates. Hen AChE presented higher ki (900.57 +/- 65.3 mM-1min-1) and, consequently, greater sensitivity to methyl-paraoxon, explained by a lower Kd (0.6 +/- 0.13 MUM). Furthermore, hen AChE did not differentiate between the propionylthiocholine and acetylthiocholine substrates, indicating easier access of methyl-paraoxon to the hen enzyme activity site. The results obtained herein indicate a suitable extraction of AChE and, despite different inhibition kinetic constants, demonstrate that fish AChE is less sensitive to methyl-paraoxon, probably due to reduced access to the catalytic center which provides greater enzyme substrate selectivity. PMID- 27655612 TI - Effect of di-n-butyl phthalate (DBP) on the fruit quality of cucumber and the health risk. AB - Di-n-butyl phthalate (DBP) widely used as plastic films' plasticizer, can cause agricultural pollution which is of increasing concern because of the food safety issues. Cucumber ( Cucumis sativus Linn.), commonly cultured in greenhouse, was exposed to DBP stress to gain more information about the ecological risk of DBP in this study. Changes of DBP residues and fruit quality of cucumber at different DBP concentrations (0, 5, 10, 20, 40 mg/kg of dry soil) were investigated in pot experiments using an agricultural soil under greenhouse condition, respectively. DBP residue in cucumber fruits ranged from 0.5326 to 1.8938 mg/kg, and the quality of cucumber fruits (organic acids, vitamin C, soluble protein, and soluble sugar) were influenced by DBP stress. Moreover, the health risk assessment was evaluated by estimate daily intakes (EDI) and the target hazard quotient (THQ) was analyzed. Under 40 mg/kg DBP condition, the highest value of EDI was 2.49 MUg/kg bw/day and the THQ ranged from 0.000700 to 0.0249. Although the risk of DBP in cucumber fruits was lower than the threshold limit value of risk, the potential health risk was not a negligible issue. PMID- 27655613 TI - The potential for constructed wetlands to treat alkaline bauxite-residue leachate: Phragmites australis growth. AB - High alkalinity (pH > 12) of bauxite-residue leachates presents challenges for the long-term storage and managements of the residue. Recent evidence has highlighted the potential for constructed wetlands to effectively buffer the alkalinity, but there is limited evidence on the potential for wetland plants to establish and grow in soils inundated with residue leachate. A pot-based trial was conducted to investigate the potential for Phragmites australis to establish and grow in substrate treated with residue leachate over a pH range of 8.6-11.1. The trial ran for 3 months, after which plant growth and biomass were determined. Concentrations of soluble and exchangeable trace elements in the soil substrate and also in the aboveground and belowground biomass were determined. Residue leachate pH did not affect plant biomass or microbial biomass. With the exception of Na, there was no effect on exchangeable trace elements in the substrate; however, increases in soluble metals (As, Cd and Na) were observed with increasing leachate concentration. Furthermore, increases in Al, As and V were observed in belowground biomass and for Cd and Cr in aboveground biomass. Concentrations within the vegetation biomass were less than critical phytotoxic levels. Results demonstrate the ability for P. australis to grow in bauxite residue leachate-inundated growth media without adverse effects. PMID- 27655614 TI - Distribution and variability of total mercury in snow cover-a case study from a semi-urban site in Poznan, Poland. AB - In the present paper, the inter-seasonal Hg variability in snow cover was examined based on multivariate statistical analysis of chemical and meteorological data. Samples of freshly fallen snow cover were collected at the semi-urban site in Poznan (central Poland), during 3-month field measurements in winter 2013. It was showed that concentrations of atmospherically deposited Hg were highly variable in snow cover, from 0.43 to 12.5 ng L-1, with a mean value of 4.62 ng L-1. The highest Hg concentration in snow cover coincided with local intensification of fossil fuel burning, indicating large contribution from various anthropogenic sources such as commercial and domestic heating, power generation plants, and traffic-related pollution. Moreover, the variability of Hg in collected snow samples was associated with long-range transport of pollutants, nocturnal inversion layer, low boundary layer height, and relatively low air temperature. For three snow episodes, Hg concentration in snow cover was attributed to southerly advection, suggesting significant contribution from the highly polluted region of Poland (Upper Silesia) and major European industrial hotspots. However, the peak Hg concentration was measured in samples collected during predominant N to NE advection of polluted air masses and after a relatively longer period without precipitation. Such significant contribution to the higher Hg accumulation in snow cover was associated with intensive emission from anthropogenic sources (coal combustion) and atmospheric conditions in this area. These results suggest that further measurements are needed to determine how the Hg transformation paths in snow cover change in response to longer/shorter duration of snow cover occurrence and to determine the interactions between mercury and absorbing carbonaceous aerosols in the light of climate change. PMID- 27655615 TI - Contaminant bioavailability in soil and phytotoxicity/genotoxicity tests in Vicia faba L.: a case study of boron contamination. AB - In this work, the model plant for genotoxicity studies Vicia faba L. was used to investigate the relation between Boron (B) content and bioavailability in soil and plant genotoxic/phytotoxic response. A total of nine soil samples were investigated: two soil samples were collected from a B-polluted industrial area in Cecina (Tuscany, Italy), the other samples were obtained by spiking control soil (from a not polluted area of the basin) with seven increased doses of B, from about 20 to 100 mg B kg-1. As expected, B availability, evaluated by chemical extraction, was higher (twofold) in spiked soils when compared with collected polluted soils with the same B total content. To analyze the phytotoxic effects of B, seed germination, root elongation, biomass production, and B accumulation in plant tissues were considered in V. faba plants grown in the various soils. Moreover, the cytotoxic/genotoxic effects of B were investigated in root meristems by mitotic index (MI) and micronuclei frequency (MCN) analysis. The results highlighted that V. faba was a B-sensitive plant and the appearance of phytotoxic effects, which altered plant growth parameters, were linearly correlated to the bioavailable B concentration in soils. Concerning the occurrence of cytotoxic/genotoxic effects induced by B, no linear correlation was observed even if MCN frequency was logarithmic correlated with the concentration of B bioavailable in soils. PMID- 27655616 TI - Occurrence of cardiovascular drugs in the sewage-impacted Vistula River and in tap water in the Warsaw region (Poland). AB - In recent years, cardiovascular diseases were the second most common cause of death worldwide. Therefore, the consumption of drugs used to treat cardiovascular diseases is high. So far, there were no such comprehensive reports regarding the presence of cardiovascular drugs in surface and tap waters, particularly in Central and Eastern Europe. The aim of our study was to determine the presence of 30 pharmaceutically active compounds and some of their metabolites, at specific points of the Vistula River and in tap water samples in the Warsaw region. The analysis was performed using the liquid chromatography-electrospray ionization tandem mass spectrometry method, coupled to solid-phase extraction. To the best of the authors' knowledge, this is the first time where the presence of ciprofibrate in the environment was investigated. Cardiovascular drugs found at the highest concentrations (reaching 1 MUg/L or higher) in surface water were beta-blockers, sartans and diuretics. In tap water samples, trace amounts of pharmaceuticals were detected, for almost all target compounds. This highlights their inadequate elimination by the treatment facility used in the Warsaw region. The presence of cardiovascular compounds in the aquatic environment could have a long-term effect even at a low exposure level, since synergy effects amongst pharmaceuticals may occur. PMID- 27655617 TI - Titanium dioxide solid phase for inorganic species adsorption and determination: the case of arsenic. AB - We have evaluated a new titanium dioxide (Adsorbsia As600) for the adsorption of both inorganic As (V) and As (III) species. In order to characterize the sorbent, batch experiments were undertaken to determine the capacities of As (III) and As (V) at pH 7.3, which were found to be 0.21 and 0.14 mmol g-1, respectively. Elution of adsorbed species was only possible using basic solutions, and arsenic desorbed under batch conditions was 50 % when 60 mg of loaded titanium dioxide was treated with 0.5 M NaOH solution. Moreover, its use as a sorbent for solid phase extraction and preconcentration of arsenic species from well waters has been investigated, without any previous pretreatment of the sample. Solid-phase extraction was implemented by packing several minicolumns with Adsorbsia As600. The method has been validated showing good accuracy and precision. Acceptable recoveries were obtained when spiked waters at 100-200 MUg L-1 were measured. The presence of major anions commonly found in waters did not affect arsenic adsoption, and only silicate at 100 mg L-1 level severely competed with arsenic species to bind to the material. Finally, the measured concentrations in water samples containing arsenic from the Pyrinees (Catalonia, Spain) showed good agreement with the ICP-MS results. PMID- 27655618 TI - Lead isotopes and heavy minerals analyzed as tools to understand the distribution of lead and other potentially toxic elements in soils contaminated by Cu smelting (Legnica, Poland). AB - Surroundings of the Legnica Cu smelter (Poland) offer insight into the behavior of Pb and other metal(oid)s in heavily contaminated soils in a relatively simple site, where lithogenic and anthropogenic Pb contributions have uniform Pb isotope composition over the time of smelter activity. Distribution of metal(oid)s decreases asymptotically with depth and below 30 cm reaches concentrations typical or lower than those of upper continental crust. Usually, such distribution is interpreted as the decrease in anthropogenic Pb contribution with depth. However, calculations based on Pb isotopes indicate that anthropogenic Pb is probably distributed both as Pb-rich particles of slags and fly ashes and Pb poor soil solutions. Generally, anthropogenic Pb constitutes up to 100 % of Pb in the uppermost 10 cm of the soils and comes often from mechanical mixing with slag and fly ash particles as well as their weathering products. On the other hand, lower soil horizon contains anthropogenic Pb in various forms, and at depths below 30 cm, most of anthropogenic Pb comes from soil solutions and can constitute from 1 to 65 % of the Pb budget. This is consistent with secondary electron microscope (SEM) analyses of heavy mineral particles showing that, in upper horizons, Pb, Cu, and Zn are contained in various particles emitted from the smelter, which show different stages of weathering. Currently, large portion of these metals may reside in the secondary Fe-hydro-oxides. On the other hand, in deeper soil horizons, anthropogenic Pb is probably dominated by Pb coming from leaching of slag or fly ash particles. Overall, metal(oid) mobility is a dynamic process and is controlled by the soil type (cultivated versus forest) and the composition and the structure of the metal-rich particles emitted from the smelter. High proportions of anthropogenic Pb at depths below 30 cm in some soil profiles indicate that Pb (and probably other metal(oid)s) can be transported down the soil profile and the present concentration of anthropogenic Pb depends on the availability of binding sites. PMID- 27655619 TI - Hydrogeochemical processes and impact of tanning industries on groundwater quality in Ambur, Vellore district, Tamil Nadu, India. AB - The present study was carried out to determine the hydrogeochemical processes and the impact of tanning industries on groundwater in Ambur, Vellore district, Tamil Nadu, India. Thirty groundwater samples were collected during pre monsoon (July 2015) and post monsoon (January 2016) from the open and shallow wells around this region and were analyzed for major ions and chromium. The major ion concentration follows the order of Na+ > Ca2+ > Mg2+ > K+ (cations) and Cl- > HCO3- > SO42- > NO3- (anions) for both seasons. The high concentrations of Na+, Cl-, and Cr around the tannery regions indicate the impact of effluent discharged from tannery units. In general, the groundwater of this study area is of Na+-Cl- type, which is due to the mixing of tannery effluent and cation exchange process. Ionic ratio indicates that the silicate weathering influences the groundwater chemistry. The permissible limit of chromium in the groundwater exceeds in over 50 % of the sampling wells. The factor analysis reveals that the dominant source for ionic contents is due to tannery effluents and cation exchange processes. To overcome this situation, it is essential to improve the performance of the effluent treatment plants so as to remove the salinity of wastewater and to plan for rainfall recharge structures for improving the groundwater recharge. PMID- 27655620 TI - Leaching of metals from large pieces of printed circuit boards using citric acid and hydrogen peroxide. AB - In the present study, the leaching of metals from large pieces of computer printed circuit boards (CPCBs) was studied. A combination of citric acid (0.5 M) and 1.76 M hydrogen peroxide (H2O2) was used to leach the metals from CPCB piece. The influence of system variables such as H2O2 concentration, concentration of citric acid, shaking speed, and temperature on the metal leaching process was investigated. The complete metal leaching was achieved in 4 h from a 4 * 4 cm CPCB piece. The presence of citric acid and H2O2 together in the leaching solution is essential for complete metal leaching. The optimum addition amount of H2O2 was 5.83 %. The citric acid concentration and shaking speed had an insignificant effect on the leaching of metals. The increase in the temperature above 30 degrees C showed a drastic effect on metal leaching process. PMID- 27655621 TI - Wastewater sludges pretreated by different oxidation systems at mild conditions to promote the biogas formation in anaerobic processes. AB - The effect of different oxidation processes at mild conditions including the coupled-Fenton (sono-Fenton, photo-Fenton, and sono-photo-Fenton) and their blank systems (ultrasound, ultraviolet, zero valent iron, and Fenton) on anaerobic digestion of the sludge for biogas production was investigated. Ultrasounds led to the highest organic matter solubilization (3.8 up to 5.2 g chemical oxygen demand (COD)/L, for the raw and treated sludge, respectively), while for the rest, organic matter transformation was observed resulting in an almost soluble COD net balance. Results indicated that for the most oxidative processes, the released organic matter was probably mineralized by the hydroxyl radicals produced during the treatments. It is interesting to remark that even if the biochemical methane potential was barely enhanced by the different methods applied, all the methods demonstrated to enhance the overall kinetics of the biomethanation processes, increasing the rapidly biodegradable fraction of the sludge. PMID- 27655622 TI - Exome Variant Analysis of Chronic Periodontitis in 2 Large Cohort Studies. AB - Periodontitis is characterized by inflammation of the gingival tissue. The main risk factors are socioeconomic factors, sex, age, smoking, and diabetes, but periodontal disease has also a genetic background. Previous genome-wide association studies failed to reveal genome-wide significant associations of single common single-nucleotide polymorphisms with chronic periodontitis. Using the Illumina ExomeChip data of 6,576 participants of the German population-based cohort studies Study of Health in Pomerania (SHIP) and SHIP-Trend, the authors performed single variant and also gene-based association studies of rare and common exonic variations on different periodontal case definitions. Although our study comprised the largest sample size to date to assess genetic predisposition for chronic periodontitis, the authors found no significant association. This study emphasizes that for chronic periodontitis, large sample sizes will be necessary to find genetic associations, even when examining rare genetic variants. PMID- 27655623 TI - Reduced Bone Stiffness in Women Is Associated with Clinical Attachment and Tooth Loss: The Study of Health in Pomerania. AB - The authors evaluated the association of reduced bone stiffness of the calcaneus with clinical attachment loss (CAL) and tooth loss. The authors analyzed data from 4,678 subjects (2,384 women), aged 20 to 88 y, from the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) and the baseline examination of the SHIP-Trend cohort. Bone stiffness, characterized by the stiffness index (SI) and the osteoporotic fracture risk (OFR), was assessed by quantitative ultrasound of the heel. SI and OFR were significantly associated with the mean CAL in women. While 1) the SI showed a significant association with the mean CAL and 2) the OFR with the median number of teeth in just the postmenopausal women, the OFR showed a significant association with mean CAL for both pre- and postmenopausal women. In postmenopausal women, a 10-unit increase in the SI was associated with a decrease in the mean CAL of 0.05 mm (95% confidence interval [CI]: -0.10 to 0.00; P = 0.046). Moreover, the adjusted median number of teeth was 21.4 (95% CI: 20.9 to 21.9) among the postmenopausal women with a low OFR, while it was 19.1 (95% CI: 17.8 to 20.3; P = 0.001) among the postmenopausal women with a high OFR. For the premenopausal women with a low OFR, the mean CAL was 1.60 mm (95% CI: 1.53 to 1.66), while for the premenopausal women with a high OFR, it was 2.24 mm (95% CI: 1.78 to 2.69; P = 0.006). Reduced bone stiffness was associated with clinical attachment and tooth loss in women but not in men. PMID- 27655624 TI - Periodontal tissue repair after sealing of the gap in vertical root fracture. AB - The aim of this study was to determine whether sealing of fracture gap using adhesive resin through the root canal can prevent inflammation of periodontal tissue, and resealing the incompletely sealed fracture gap from outside can resolve such inflammation in experimentally created vertical root fractures. Vertical root fractures were created in incisor of beagles. In the experimental group, the fracture gap was sealed through the root canal with adhesive resin. After 5 weeks, sites with the clinical attachment level >=4 mm were further divided randomly into the poor-replanting group and the poor-untreated group. In the poor-replanting group, the tooth was extracted and replanted after resealing the fracture gap with adhesive resin from the outer surface. Sites with clinical attachment level <=3 mm after 5 weeks were considered as the satisfactory group. The poor-untreated group and the satisfactory group were subjected to no further treatment. The clinical attachment level was evaluated at baseline and after 2, 5, and 9 weeks. After 9 weeks, histological measurements were made to determine the length of the epithelial downgrowth and the area of alveolar bone resorption. The clinical attachment level and the area of bone resorption were significantly smaller in the poor-replanting group and the satisfactory group than in the poor untreated group (p < 0.05). The results indicate the possibility that periodontal inflammation along the fracture line can be prevented and improved if the fracture gap is sealed. PMID- 27655626 TI - Autoinflammation and Immunomodulation in Inflammatory Fibromyalgia Syndrome- A Review. AB - Generalized pain with tender points in specific areas accompanied by systemic symptoms such as fatigue and stiffness is characteristic of fibromyalgia (FM) syndrome. The genesis of FM is still being investigated with conflicting data on factors including autonomic dysfunction, neurotransmitters, and hormones often in combination with external stressful events. However, recent research is starting to suggest that there is a previously underappreciated subtype of fibromyalgia called inflammatory Fibromyalgia (iFM). Recent studies have described cytokines, inflammatory markers, sleep disorders, hyperalgesia, cognitive dysfunction, serum leptin levels and other inflammatory indicators as potential markers for iFM. This article will; 1) review the inflammatory markers and abnormal levels of other laboratory indicators that can help to identify the subgroup of patients that fall into the new category of Inflammatory Fibromyalgia [1-5] and 2) review all completed trials that were focused on treating this new category of disease. Through this review it is hoped that and further understanding of the complexity of the etiology of fibromyalgia can be explored. PMID- 27655625 TI - Caries diagnosis using light fluorescence devices in comparison with traditional visual and tactile evaluation: a prospective study in 152 patients. AB - The objective of the study was to evaluate the in vivo effectiveness of two fluorescence techniques (DIAGNOdent and VistaProof) and of visual and tactile evaluation in the diagnosis of occlusal caries in permanent teeth. A total of 302 teeth (molars and premolars) from 152 patients were studied. The occlusal surfaces were cleaned using pumice mixed with water, followed by application of the diagnostic methods according to the instructions of the manufacturer, and of the visual and tactile methods according to the recommendations. The true extent of the lesions was determined by fissurotomy. The sensitivity and specificity of visual diagnosis were 79 and 72 %, respectively, versus 53 and 98 % in the case of tactile diagnosis. Teeth with caries lesions exhibited significantly higher DIAGNOdent and VistaProof scores than those without caries. Using the optimum cutoff point of 23.5 obtained in our study for DIAGNOdent, sensitivity and specificity were found to be 92.4 and 92.7 %, respectively, while values of 88.1 and 95.1 % were obtained with a cutoff point of 28.5. Sensitivity in the case of the VistaProof system varied between 92.9 % (cutoff point 1.05) and 85.3 % (cutoff point 1.3), with respective specificity values of 95.8 and 88.6 %. The areas under the curve were 0.756, 0.759, 0.954 and 0.965 for the visual and tactile methods and for DIAGNOdent and VistaProof, respectively. The fluorescence based techniques showed greater internal and external validity than the visual and tactile methods in diagnosing occlusal caries in permanent teeth. VistaProof is the best method for diagnosing caries in its early stages. PMID- 27655627 TI - Repair of human periodontal bone defects by autologous grafting stem cells derived from inflammatory dental pulp tissues. AB - BACKGROUND: Recently, stem cells derived from inflammatory dental pulp tissues (DPSCs-IPs) have demonstrated regenerative potential, but the real effect remains to be examined. This pilot study attempted to isolate DPSCs-IPs from two patients and to evaluate the feasibility and the effect of reconstructing periodontal intrabone defects in each patient. METHODS: DPSCs-IPs were harvested from two patients with periodontal intrabone defects with their approval. After discussing the biological characteristics of DPSCs-IPs in each patient, DPSCs-IPs were loaded onto the scaffold material beta-tricalcium phosphate and engrafted into the periodontal defect area in the root furcation. After 1, 3, and 9 months, the outcome was evaluated by clinical assessment and radiological study. Furthermore, new samples were collected and the biological characteristics of DPSCs-IPs were further studied compared with normal dental pulp stem cells. The primary cell culture success rate, cell viability, cell cycle analysis, and proliferation index were used to describe the growth state of DPSCs-IPs. In-vitro differentiation ability detection was used to further discuss the stem cell characteristics of DPSCs-IPs. RESULTS: As expected, DPSCs-IPs were able to engraft and had an effect of regeneration of new bones to repair periodontal defects 9 months after surgical reconstruction. Although the success rate of primary cell culture and growth status was slightly inhibited, DPSCs-IPs expressed comparable levels of stem cell markers as well as retaining their multidifferentiation ability. CONCLUSIONS: We developed a standard procedure that is potentially safe and technological for clinical periodontal treatment using human autologous DPSCs-IPs. TRIAL REGISTRATION: According to the editorial policies, the present study is a purely observational study, so trial registration is not required. PMID- 27655628 TI - Patient Centered Medical Home Care Among Near-Old and Older Race/Ethnic Minorities in the US: Findings from the Medical Expenditures Panel Survey. AB - Access to Patient Centered Medical Home (PCMH) care has not been explored among older racial/ethnic minorities. We used data on adults 55-years and older from the Medical Expenditure Panel Survey (2008-2013). We account for five features of PCMH experiences and focus on respondents self-identifying as Non-Latino White, Black, and Latino. We used regression models to examine associations between PCMH care and its domains and race/ethnicity and decomposition techniques to assess contribution to differences by predisposing, enabling and health need factors. We found low overall access and significant racial/ethnic variations in experiences of PCMH. Our results indicated strong deficiencies in access to a personal primary care physician provided healthcare. Factors contributing to differences in reported PCMH experiences relative to Whites differed by racial/ethnic grouping. Policy initiatives aimed at addressing accessibility to personal physician directed healthcare could potentially reduce racial/ethnic differences while increasing national access to PCMH care. PMID- 27655630 TI - A highly specific sodium aptamer probed by 2-aminopurine for robust Na+ sensing. AB - Sodium is one of the most abundant metals in the environment and in biology, playing critical ecological and physiological roles. Na+ is also the most common buffer salt for nucleic acids research, while its specific interaction with DNA has yet to be fully studied. Herein, we probe a highly selective and robust Na+ aptamer using 2-aminopurine (2AP), a fluorescent adenine analog. This aptamer has two DNA strands derived from the Ce13d DNAzyme. By introducing a 2AP at the cleavage site of the substrate strand, Na+ induces ~40% fluorescence increase. The signaling is improved by a series of rational mutations, reaching >600% with the C10A20 double mutant. This fluorescence enhancement suggests relaxed base stacking near the 2AP label upon Na+ binding. By replacing a non-conserved adenine in the enzyme strand by 2AP, Na+-dependent fluorescence quenching is observed, suggesting that the enzyme loop folds into a more compact structure upon Na+ binding. The fluorescence changes allow for Na+ detection. With an optimized sequence, a detection limit of 0.4 mM Na+ is achieved, reaching saturated signal in less than 10 s. The sensor response is insensitive to ionic strength, which is critical for Na+ detection. PMID- 27655632 TI - Casposon integration shows strong target site preference and recapitulates protospacer integration by CRISPR-Cas systems. AB - Casposons are a recently discovered group of large DNA transposons present in diverse bacterial and archaeal genomes. For integration into the host chromosome, casposons employ an endonuclease that is homologous to the Cas1 protein involved in protospacer integration by the CRISPR-Cas adaptive immune system. Here we describe the site-preference of integration by the Cas1 integrase (casposase) encoded by the casposon of the archaeon Aciduliprofundum boonei Oligonucleotide duplexes derived from the terminal inverted repeats (TIR) of the A. boonei casposon as well as mini-casposons flanked by the TIR inserted preferentially at a site reconstituting the original A. boonei target site. As in the A. boonei genome, the insertion was accompanied by a 15-bp direct target site duplication (TSD). The minimal functional target consisted of the 15-bp TSD segment and the adjacent 18-bp sequence which comprises the 3' end of the tRNA-Pro gene corresponding to the TPsiC loop. The functional casposase target site bears clear resemblance to the leader sequence-repeat junction which is the target for protospacer integration catalyzed by the Cas1-Cas2 adaptation module of CRISPR Cas. These findings reinforce the mechanistic similarities and evolutionary connection between the casposons and the adaptation module of the prokaryotic adaptive immunity systems. PMID- 27655634 TI - Furoquinoline Alkaloids and Methoxyflavones from the Stem Bark of Melicope madagascariensis (Baker) T.G. Hartley. AB - Melicope madagascariensis (Rutaceae) is an endemic plant species of Madagascar that was first classified as a member of the genus Euodia J. R. & G. Forst (Rutaceae) under the scientific name Euodia madagascariensis Baker. Based on morphological characteristics, Thomas Gordon Hartley taxonomically revised E. madagascariensis Baker to be M. madagascariensis (Baker) T.G. Hartley. Chemotaxonomical studies have long been used to help the identification and confirmation of taxonomical classification of plant species and botanicals. Aiming to find more evidences to support the taxonomical revision performed on E. madagascariensis, we carried out phytochemical investigation of two samples of the plant. Fractionation of the ethanol extracts prepared from two stem bark samples of M. madagascariensis (Baker) T.G. Hartley led to the isolation of seven known furoquinoline alkaloids 1-7 and two known methoxyflavones 8 and 9. The presence of furoquinoline alkaloids and methoxyflavones in the title species is in agreement with its taxonomic transfer from Euodia to Melicope. Antiprotozoal evaluation of the isolated compounds showed that 6-methoxy-7-hydroxydictamnine (heliparvifoline, 3) showed weak antimalarial activity (IC50 = 35 uM) against the chloroquine-resistant strain Dd2 of Plasmodium falciparum. Skimmianine (4) displayed moderate cytotoxicity with IC50 value of 1.5 uM against HT-29 colon cancer cell line whereas 3,5-dihydroxy-3',4',7-trimethoxyflavone (9) was weakly active in the same assay (IC50 = 13.9 uM). PMID- 27655631 TI - Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice. AB - The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations. PMID- 27655635 TI - Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers. AB - Diabetic foot ulcers affect 15-20 % of all diabetic patients and remain an important challenge since the available therapies have limited efficacy and some of the novel therapeutic approaches, which include growth factors and stem cells, are highly expensive and their safety remains to be evaluated. Despite its low cost and safety, the interest for topical insulin as a healing agent has increased only in the last 20 years. The molecular mechanisms of insulin signaling and its metabolic effects have been well studied in its classical target tissues. However, little is known about the specific effects of insulin in healthy or even diabetic skin. In addition, the mechanisms involved in the effects of insulin on wound healing have been virtually unknown until about 10 years ago. This paper will review the most recent advances in the cellular and molecular mechanisms that underlie the beneficial effects of insulin on skin wound healing in diabetes. Emerging evidence that links dysfunction of key cellular organelles, namely the endoplasmic reticulum and the mitochondria, to changes in the autophagy response, as well as the impaired wound healing in diabetic patients will also be discussed along with the putative mechanisms whereby insulin could regulate/modulate these alterations. PMID- 27655633 TI - Dynamic peptides of human TPP1 fulfill diverse functions in telomere maintenance. AB - Telomeres are specialized nucleoprotein complexes that comprise the ends of linear chromosomes. Human telomeres end in a short, single-stranded DNA (ssDNA) overhang that is recognized and bound by two telomere proteins, POT1 and TPP1. Whereas POT1 binds directly to telomere ssDNA, its interaction with TPP1 is essential for localization of POT1 to the telomere. TPP1 also provides enhanced binding and sequence discrimination that regulates POT1-TPP1 interactions exclusively with telomere ssDNA. Finally, TPP1 recruits telomerase, the enzyme responsible for synthesis of telomere DNA, to the telomere. While the oligosaccharide-oligonucleotide-binding (OB)-fold domain of TPP1 has been solved by X-ray crystallography, the molecular interactions within the POT1-TPP1-ssDNA ternary complex and the conformational changes that contribute to its diverse functions remain ambiguous. We employed hydrogen/deuterium exchange combined with mass spectrometry to identify three peptides, all residing within the OB-fold of TPP1, that exhibit altered exchange rates upon complex formation or ssDNA binding. Mutation of these regions combined with functional assays revealed the diverse contributions of each moiety in protein-protein interactions, regulating telomerase activity or DNA-binding. Together, these functional data combined with biophysical analyses and homology modeling provide a molecular understanding of the diverse contributions of TPP1 in telomere maintenance. PMID- 27655637 TI - COL3A1 and SNAP91: novel glioblastoma markers with diagnostic and prognostic value. AB - Although patients with glioblastoma (GBM) have grave prognosis, significant variability in patient outcome is observed. This study aims to identify novel targets for GBM diagnosis and therapy. Microarray data (GSE4290, GSE7696, and GSE4412) obtained from the Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) by significant analysis of microarray (SAM). Intersection of the identified DEGs for each profile revealed 46 DEGs in GBM. A subset of common DEGs were validated by real-time reverse transcription quantitative PCR (qPCR). The prognostic value of some of the markers was also studied. We determined that RRM2 and COL3A1 were increased and directly correlated with glioma grade, while SH3GL2 and SNAP91 were decreased in GBM and inversely correlated with glioma grade. Kaplan-Meir analysis of GSE7696 revealed that COL3A1 and SNAP91 correlated with survival, suggesting that COL3A1 and SNAP91 may be suitable biomarkers for diagnostic or therapeutic strategies for GBM. PMID- 27655639 TI - Analysis of the variability among radiation oncologists in delineation of the postsurgical tumor bed based on 4D-CT. AB - OBJECTIVE: This study investigated interobserver and intraobserver variability in radiation oncologists' definition of the tumor bed (TB) after breast-conserving surgery (BCS). RESULTS: The TB volume, CVS and number of surgical clips were not significantly related to intraobserver variability. Moreover, no correlation was noted between CT slice thickness and interobserver variability (Deltainter, DSCinter) in TB delineation, and no significant difference was noted among the three groups. The TB volume was negatively correlated with Deltainter. DSCinter improved significantly with increased TB volume and decreased Deltainter. DSCinter also increased significantly in patients with a CVS of 3 to 5 compared with patients with a CVS of 1 to 2. DSCinter was thus positively correlated with the CVS, with a correlation coefficient of 0.451. The use of 7 to 9 surgical clips neither decreased Deltainter nor increased DSCinter. MATERIALS AND METHODS: Five or more surgical clips were placed at the TB during lumpectomy. The TB was delineated on the end expiration scan. The data were stratified based on the cavity visualization score (CVS), CT slice thickness and surgical clip number. The Dice similarity coefficient (DSC) and inter(intra)observer variability (Deltainter and Deltaintra) in different groups were evaluated and compared. CONCLUSIONS: Inter(intra)observer variability in TB delineation was decreased for breast cancer patients implanted with 5 or more surgical clips in the cohort with a higher CVS and a larger TB. The use of more than 6 surgical clips did not significantly improve TB delineation, so 5 to 6 surgical clips are likely adequate to delineate the TB. PMID- 27655638 TI - Decreased expression of IDH1-R132H correlates with poor survival in gastrointestinal cancer. AB - Isocitrate dehydrogenase (IDH1) is an NADP-dependent enzyme that catalyzes the decarboxylation of isocitrate to alpha-ketoglutarate. The IDH1-R132H mutation predicts a better clinical outcome for glioma patients, and the expression of IDH1-R132H correlates with a favorable outcome in patients with brain tumors. Here, we investigated IDH1-R132H expression in both gastric (n=526) and colorectal (n=399) tissues by performing immunohistochemistry analyses on tissue microarrays. We also tested whether IDH1-R132H expression correlated with various clinical parameters. In both gastric and colorectal cancer, expression of IDH1 R132H was associated with tumor stage. Patients with low IDH1-R132H expression had a poor overall survival. Our data indicate that IDH1-R132H expression could be used as a predictive marker of prognosis for patients with gastrointestinal cancer. PMID- 27655640 TI - Primary and recurrent ovarian high-grade serous carcinomas display similar microRNA expression patterns relative to those of normal ovarian tissue. AB - Most patients with epithelial ovarian cancer eventually die due to recurrence. However, little is known about the microRNA (miRNA) expression pattern and its involvement in recurrent ovarian cancer. We analyzed miRNA expression profiles related to the recurrence of advanced ovarian high-grade serous carcinoma (HGSC) using miRNA microarrays. Between May 2006 and December 2012, 37 ovarian HGSC patients underwent secondary cyto-debulking surgery at recurrence. Among them, only 8 pairs of primary and recurrent tumor samples were deemed to be adequate for analysis. The expression profiles of primary ovarian HGSC compared with normal ovarian tissue were significantly consistent with those of recurrent ovarian HGSC compared with normal ovarian tissue (correlation coefficient = 0.81, P = 0.0078). Among 31 miRNAs that increased by more than 4-fold in primary tumors compared with normal ovarian tissue, 27 were also significantly increased in recurrent tumor samples. Likewise, among 35 miRNAs that decreased by more than 4 fold in primary tumors compared with normal ovarian tissue, 34 were also significantly decreased in recurrent tumor samples. We identified 60 miRNAs that were significantly increased in recurrent serous ovarian carcinoma compared with primary tumor tissue, including miR-630, miR-370, and miR-575. Additionally, 52 miRNAs were significantly decreased in recurrent samples, including miR-509-3p, miR-514a-3p, and miR-506-3p. Our results demonstrate that primary and recurrent ovarian HGSC displayed similar miRNA expression patterns. Nevertheless, altered miRNA expression could be implicated in the recurrence of ovarian HGSC, and further study is needed to validate these data in independent cases using a homogeneous methodology. PMID- 27655641 TI - Uncovering synthetic lethal interactions for therapeutic targets and predictive markers in lung adenocarcinoma. AB - Two genes are called synthetic lethal (SL) if their simultaneous mutation leads to cell death, but mutation of either individual does not. Targeting SL partners of mutated cancer genes can selectively kill cancer cells, but leave normal cells intact. We present an integrated approach to uncover SL gene pairs as novel therapeutic targets of lung adenocarcinoma (LADC). Of 24 predicted SL pairs, PARP1-TP53 was validated by RNAi knockdown to have synergistic toxicity in H1975 and invasive CL1-5 LADC cells; additionally FEN1-RAD54B, BRCA1-TP53, BRCA2-TP53 and RB1-TP53 were consistent with the literature. While metastasis remains a bottleneck in cancer treatment and inhibitors of PARP1 have been developed, this result may have therapeutic potential for LADC, in which TP53 is commonly mutated. We also demonstrated that silencing PARP1 enhanced the cell death induced by the platinum-based chemotherapy drug carboplatin in lung cancer cells (CL1-5 and H1975). IHC of RAD54B?, BRCA1?-RAD54B?, FEN1(N)?-RAD54B? and PARP1? RAD54B? were shown to be prognostic markers for 131 Asian LADC patients, and all markers except BRCA1?-RAD54B? were further confirmed by three independent gene expression data sets (a total of 426 patients) including The Cancer Genome Atlas (TCGA) cohort of LADC. Importantly, we identified POLB-TP53 and POLB as predictive markers for the TCGA cohort (230 subjects), independent of age and stage. Thus, POLB and POLB-TP53 may be used to stratify future non-Asian LADC patients for therapeutic strategies. PMID- 27655642 TI - Second-generation proteasome inhibitor carfilzomib enhances doxorubicin-induced cytotoxicity and apoptosis in breast cancer cells. AB - Proteasome inhibition is an attractive approach for anticancer therapy. Doxorubicin (DOX) is widely used for treatment in a number of cancers including breast cancer; however, the development of DOX resistance largely limits its clinical application. One of the possible mechanisms of DOX-resistance is that DOX might induce the activation of NF-kappaB. In this case, proteasome inhibitors could inhibit the activation of NF-kappaB by blocking inhibitory factor kappaB (IkappaB) degradation. Carfilzomib, a second-generation proteasome inhibitor, overcomes bortezomib resistance and lessens its side-effects. Currently, the effect of carfilzomib on breast cancer cell proliferation remains unclear. In this study, we exploited the role of carfilzomib in seven breast cancer cell lines, MCF7, T-47D, MDA-MB-361, HCC1954, MDA-MB-468, MDA-MB-231, and BT-549, representing all major molecular subtypes of breast cancer. We found that carfilzomib alone had cytotoxic effects on the breast cancer cells and it increased DOX-induced cytotoxic effects and apoptosis in combination by enhancing DOX-induced JNK phosphorylation and inhibiting DOX-induced IkappaBalpha degradation. The results suggest that carfilzomib has potent antitumor effects on breast cancer in vitro and can sensitize breast cancer cells to DOX treatment. DOX in combination with carfilzomib may be an effective and feasible therapeutic option in the clinical trials for treating breast cancer. PMID- 27655643 TI - Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC. AB - BACKGROUND: No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. PATIENTS AND METHODS: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m2, every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m2, every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression free and overall survival were analysed with multivariable Cox model. RESULTS: After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. CONCLUSION: These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted. PMID- 27655644 TI - Genetic inhibition of autophagy promotes p53 loss-of-heterozygosity and tumorigenesis. AB - Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays an essential role in enabling eukaryotic organisms to adapt to nutrient deprivation and other forms of environmental stress. In metazoan organisms, autophagy is essential for differentiation and normal development; however, whether the autophagy pathway promotes or inhibits tumorigenesis is controversial, and the possible mechanisms linking defective autophagy to cancer remain unclear. To determine if autophagy is important for tumor suppression, we inhibited autophagy in transgenic zebrafish via stable, tissue-specific expression of a dominant-negative autophagy protein Atg5K130R. In heterozygous tp53 mutants, expression of dominant-negative atg5K130R increased tumor incidence and decreased tumor latency compared to non-transgenic heterozygous tp53 mutant controls. In a tp53-deficient background, Tg(mitfa:atg5K130R) mutantsdeveloped malignant peripheral nerve sheath tumors (MPNSTs), neuroendocrine tumors and small-cell tumors. Expression of a Sox10-dependent GFP transgene in the tumors demonstrated their origin from neural crest cells, lending support to a model in which mitfa-expressing cells can arise from sox10+ Schwann cell precursors. Tumors from the transgenic animals exhibited increased DNA damage and loss-of heterozygosity of tp53. Taken together, our data indicate that genetic inhibition of autophagy promotes tumorigenesis in tp53 mutant zebrafish, and suggest a possible role for autophagy in the regulation of genome stability during oncogenesis. PMID- 27655645 TI - Early detection of pemetrexed-induced inhibition of thymidylate synthase in non small cell lung cancer with FLT-PET imaging. AB - Inhibition of thymidylate synthase (TS) results in a transient "flare" in DNA thymidine salvage pathway activity measurable with FLT ([18F]thymidine)-positron emission tomography (PET). Here we characterize this imaging strategy for potential clinical translation in non-small cell lung cancer (NSCLC). Since pemetrexed acts by inhibiting TS, we defined the kinetics of increases in thymidine salvage pathway mediated by TS inhibition following treatment with pemetrexed in vitro. Next, using a mouse model of NSCLC, we validated the kinetics of the pemetrexed-mediated "flare" in thymidine salvage pathway activity in vivo using FLT-PET imaging. Finally, we translated our findings into a proof of-principle clinical trial of FLT-PET in a human NSCLC patient. In NSCLC cells in vitro, we identified a burst in pemetrexed-mediated thymidine salvage pathway activity, assessed by 3H-thymidine assays, thymidine kinase 1 (TK1) expression, and equilibrative nucleoside transporter 1 (ENT1) mobilization to the cell membrane, that peaked at 2hrs. This 2hr time-point was also optimal for FLT-PET imaging of pemetrexed-mediated TS inhibition in murine xenograft tumors and was demonstrated to be feasible in a NSCLC patient. FLT-PET imaging of pemetrexed induced TS inhibition is optimal at 2hrs from therapy start; this timing is feasible in human clinical trials. PMID- 27655646 TI - The effects of intravenous anesthetics on QT interval during anesthetic induction with sevoflurane. AB - PURPOSE: Sevoflurane is known to prolong the QT interval. This study aimed to determine the effect of the interaction between intravenous anesthetics and sevoflurane on the QT interval. METHODS: The study included 48 patients who underwent lumbar spine surgery. Patients received 3 MUg/kg fentanyl and were then randomly allocated to either Group T, in which they received 5 mg/kg thiamylal, or Group P, in which they received 1.5 mg/kg propofol, at 2 min after administration of fentanyl injection for anesthetic induction. Vecuronium (1.5 mg/kg) and sevoflurane (3 % inhaled concentration) were administered immediately after loss of consciousness and tracheal intubation was performed 3 min after vecuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram were recorded immediately before fentanyl administration (T1), 2 min after fentanyl injection (T2), immediately before intubation (T3), and 2 min after intubation (T4). RESULTS: There were no significant differences between the two groups in baseline patient characteristics. BIS and MAP significantly decreased after anesthesia induction in both groups. At T3, MAP in Group T was higher than in Group P, while HR had reduced in both groups. The QTc interval was prolonged after anesthesia induction in Group T, but did not change at any time point in Group P. The QTc interval after anesthesia induction in Group T was longer than in Group P. CONCLUSION: We concluded that an injection of propofol could counteract QTc interval prolongation associated with sevoflurane anesthesia induction. PMID- 27655647 TI - Expert consensus on facilitators and barriers to return-to-work following surgery for non-traumatic upper extremity conditions: a Delphi study. AB - : This Delphi study aimed to reach consensus on important facilitators and barriers for return-to-work following surgery for non-traumatic upper extremity conditions. In Round 1, experts ( n = 42) listed 134 factors, which were appraised in Rounds 2 and 3. Consensus (?85% agreement) was achieved for 13 facilitators (high motivation to return-to-work; high self-efficacy for return-to work and recovery; availability of modified/alternative duties; flexible return to-work arrangements; positive coping skills; limited heavy work exertion; supportive return-to-work policies; supportive supervisor/management; no catastrophic thinking; no fear avoidance to return-to-work; no fear avoidance to pain/activity; return to meaningful work duties; high job satisfaction) and six barriers (mood disorder diagnosis; pain/symptoms at more than one musculoskeletal site; heavy upper extremity exertions at work; lack of flexible return-to-work arrangements; lack of support from supervisor/management; high level of pain catastrophizing). Future prognostic studies are required to validate these biopsychosocial factors to further improve return-to-work outcomes. LEVEL OF EVIDENCE: V. PMID- 27655648 TI - Outcomes of a 'One Health' Monitoring Approach to a Five-Year Beaver (Castor fiber) Reintroduction Trial in Scotland. AB - The Scottish Beaver Trial, involving the translocation and release of 16 wild Norwegian beavers (Castor fiber) to Scotland, provides a good example of a 'One Health' scientific monitoring approach, with independent monitoring partners on ecology and public health feeding into veterinary health surveillance. Pathogen detection did not prohibit beaver release, although eight beavers were seropositive for Leptospira spp. Six deaths (37.5%) occurred during Rabies quarantine, followed by the death of two animals shortly after release and two wild-born kits due to suspected predation. Two host-specific parasites, the beaver fluke (Stichorchis subtriquetrus) and beaver beetle (Platypsyllus castoris) were also reintroduced. PMID- 27655636 TI - Kinase inhibitors as potential agents in the treatment of multiple myeloma. AB - Recent years have witnessed a dramatic increase in the number of therapeutic options available for the treatment of multiple myeloma (MM) - from immunomodulating agents to proteasome inhibitors to histone deacetylase (HDAC) inhibitors and, most recently, monoclonal antibodies. Used in conjunction with autologous hematopoietic stem cell transplantation, these modalities have nearly doubled the disease's five-year survival rate over the last three decades to about 50%. In spite of these advances, MM still is considered incurable as resistance and relapse are common. While small molecule protein kinase inhibitors have made inroads in the therapy of a number of cancers, to date their application to MM has been less than successful. Focusing on MM, this review examines the roles played by a number of kinases in driving the malignant state and the rationale for target development in the design of a number of kinase inhibitors that have demonstrated anti-myeloma activity in both in vitro and in vivo xenograph models, as well as those that have entered clinical trials. Among the targets and their inhibitors examined are receptor and non-receptor tyrosine kinases, cell cycle control kinases, the PI3K/AKT/mTOR pathway kinases, protein kinase C, mitogen-activated protein kinase, glycogen synthase kinase, casein kinase, integrin-linked kinase, sphingosine kinase, and kinases involved in the unfolded protein response. PMID- 27655650 TI - Aortic valve disease 2016: evaluation for and outcome of TAVI and surgery. PMID- 27655649 TI - Impact of Anthropogenic Disturbance on Native and Invasive Trypanosomes of Rodents in Forested Uganda. AB - Habitat disturbance and anthropogenic change are globally associated with extinctions and invasive species introductions. Less understood is the impact of environmental change on the parasites harbored by endangered, extinct, and introduced species. To improve our understanding of the impacts of anthropogenic disturbance on such host-parasite interactions, we investigated an invasive trypanosome (Trypanosoma lewisi). We screened 348 individual small mammals, representing 26 species, from both forested and non-forested habitats in rural Uganda. Using microscopy and PCR, we identified 18% of individuals (order Rodentia) as positive for trypanosomes. Further phylogenetic analyses revealed two trypanosomes circulating-T. lewisi and T. varani. T. lewisi was found in seven species both native and invasive, while T. varani was identified in only three native forest species. The lack of T. varani in non-forested habitats suggests that it is a natural parasite of forest-dwelling rodents. Our findings suggest that anthropogenic disturbance may lead to spillover of an invasive parasite (T. lewisi) from non-native to native species, and lead to local co extinction of a native parasite (T. varani) and native forest-dwelling hosts. PMID- 27655651 TI - Victor Dzau MD. PMID- 27655653 TI - British Cardiovascular Society Annual Conference 2016. PMID- 27655655 TI - Can SNOMED CT be squeezed without losing its shape? AB - BACKGROUND: In biomedical applications where the size and complexity of SNOMED CT become problematic, using a smaller subset that can act as a reasonable substitute is usually preferred. In a special class of use cases-like ontology based quality assurance, or when performing scaling experiments for real-time performance-it is essential that modules show a similar shape than SNOMED CT in terms of concept distribution per sub-hierarchy. Exactly how to extract such balanced modules remains unclear, as most previous work on ontology modularization has focused on other problems. In this study, we investigate to what extent extracting balanced modules that preserve the original shape of SNOMED CT is possible, by presenting and evaluating an iterative algorithm. METHODS: We used a graph-traversal modularization approach based on an input signature. To conform to our definition of a balanced module, we implemented an iterative algorithm that carefully bootstraped and dynamically adjusted the signature at each step. We measured the error for each sub-hierarchy and defined convergence as a residual sum of squares <1. RESULTS: Using 2000 concepts as an initial signature, our algorithm converged after seven iterations and extracted a module 4.7 % the size of SNOMED CT. Seven sub-hierarhies were either over or under-represented within a range of 1-8 %. CONCLUSIONS: Our study shows that balanced modules from large terminologies can be extracted using ontology graph traversal modularization techniques under certain conditions: that the process is repeated a number of times, the input signature is dynamically adjusted in each iteration, and a moderate under/over-representation of some hierarchies is tolerated. In the case of SNOMED CT, our results conclusively show that it can be squeezed to less than 5 % of its size without any sub-hierarchy losing its shape more than 8 %, which is likely sufficient in most use cases. PMID- 27655657 TI - Getting the dose right for obese children. PMID- 27655658 TI - Obesity in adolescents with chronic fatigue syndrome: an observational study. AB - OBJECTIVE: Identify the prevalence of obesity in patients with chronic fatigue syndrome (CFS) compared with healthy adolescents, and those identified with CFS in a population cohort. DESIGN: Cross-sectional analysis of multiple imputed data. SETTING: Data from UK paediatric CFS/myalgic encephalomyelitis (CFS/ME) services compared with data collected at two time points in the Avon Longitudinal Study of Parents and Children (ALSPAC). PATIENTS: 1685 adolescents who attended a CFS/ME specialist service between 2004 and 2014 and 13 978 adolescents aged approximately 13 years and 16 years participating in the ALSPAC study. MAIN OUTCOME MEASURES: Body mass index (BMI) (kg/m2), sex-specific and age-specific BMI Z-scores (relative to the International Obesity Task Force cut-offs) and prevalence of obesity (%). RESULTS: Adolescents who had attended specialist CFS/ME services had a higher prevalence of obesity (age 13 years: 9.28%; age 16 years: 16.43%) compared with both adolescents classified as CFS/ME in ALSPAC (age 13 years: 3.72%; age 16 years: 5.46%) and those non-CFS in ALSPAC (age 13 years: 4.18%; age 16 years: 4.46%). The increased odds of obesity in those who attended specialist services (relative to non-CFS in ALSPAC) was apparent at both 13 years (OR: 2.31 (1.54 to 3.48)) and 16 years, with a greater likelihood observed at 16 years (OR: 4.07 (2.04 to 8.11)). CONCLUSIONS: We observed an increased prevalence of obesity in adolescents who were affected severely enough to be referred to a specialist CFS/ME service. Further longitudinal research is required in order to identify the temporal relationship between the two conditions. PMID- 27655659 TI - QUESTION 1: Does folic acid supplementation reduce the incidence or severity of anaemia in neonates with a positive direct Coombs test? PMID- 27655660 TI - Arthritis in children: comparison of clinical and biological characteristics of septic arthritis and juvenile idiopathic arthritis. AB - AIM: Childhood arthritis arises from several causes. The aim of this observational study is to compare the clinical and biological features and short term outcome of different types of arthritis because they have different treatment and prognoses. METHODS: Children <16 years of age hospitalised in a French tertiary care centre for a first episode of arthritis lasting for less than 6 weeks who underwent joint aspiration were retrospectively included. We performed non-parametrical tests to compare groups (septic arthritis (SA), juvenile idiopathic arthritis (JIA) and arthritis with no definitive diagnosis). The time before apyrexia or C reactive protein (CRP) <10 mg/L was analysed using the Kaplan-Meier method. RESULTS: We studied 125 children with a sex ratio (M/F) of 1.1 and a median age of 2.2 years (range 0.3 to 14.6). SA was associated with a lower age at onset (1.5 years, IQR 1.2-3.0 vs 3.6 years, IQR 2.2-5.6), shorter duration of symptoms before diagnosis (2 days, IQR 1-4 vs 7 days, IQR 1-19) and higher synovial white blood cell count (147 cells *103/mm3, IQR 71-227, vs 51 cells *103/mm3, IQR 12-113), than JIA. Apyrexia occurred later in children with JIA (40% after 2 days, 95% CI 17% to 75%) than children with SA (82%, 95% CI 68% to 92%), as did CRP<10 mg/L (18% at 7 days, 95% CI 6.3% to 29.6% vs 82.1%, 95% CI 76.1% to 89.7%, p=0.01). CONCLUSIONS: There were no sufficiently reliable predictors for differentiating between SA and JIA at onset. The outcomes were different; JIA should be considered in cases of poor disease evolution after antibiotic treatment and joint aspiration. PMID- 27655661 TI - Ulcerative skin lesions following varicella infection. PMID- 27655663 TI - Locked nucleic acid-inhibitor of miR-205 decreases endometrial cancer cells proliferation in vitro and in vivo. AB - Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up-regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo.In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1/cmdb mice bearing endometrial cancer xenografts were intraperitoneally injected with nine dosages of 25mg/kg of miR-205-LNA-inhibitor or scramble control or phosphatase buffered saline and were observed for 32 days. We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals.In conclusion our results suggest that systemic delivery of miR 205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer. Therefore it warrants further studies in other animal models. PMID- 27655662 TI - Anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors as combination therapy for triple-negative breast cancer. AB - Triple-negative breast cancer (TNBC) is characterized by overexpression of epidermal growth factor receptor (EGFR) and activation of its downstream signaling pathways. Dual targeting of EGFR using one monoclonal antibody (mAb; cetuximab or panitumumab) and one tyrosine kinase inhibitor (EGFR-TKI; gefitinib or erlotinib) is a potential therapeutic approach. We investigated the effect of these therapies in EGFR-expressing TNBC cell lines that do or do not harbor the main activating mutations of EGFR pathways. Cell lines were sensitive to EGFR TKIs, whereas mAbs were active only in MDA-MB-468 (EGFR amplification) and SUM 1315 (KRAS and PTEN wild-type) cells. MDA-MB-231 (KRAS mutated) and HCC-1937 (PTEN deletion) cells were resistant to mAbs. The combined treatment resulted in a synergistic effect on cell proliferation and superior inhibition of the RAS/MAPK signaling pathway in mAb-sensitive cells. The anti-proliferative effect was associated with G1 cell cycle arrest followed by apoptosis. Sensitivity to therapies was characterized by induction of positive regulators and inactivation of negative regulators of cell cycle. These results suggest that dual EGFR inhibition might result in an enhanced antitumor effect in a subgroup of TNBC. The status of EGFR, KRAS and PTEN could be used as a molecular marker for predicting the response to this therapeutic strategy. PMID- 27655664 TI - Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats. AB - The blood-brain barrier (BBB) is the major clinical obstacle in the chemotherapeutic management of brain glioma. Here we synthesized a pH-sensitive dual-targeting doxorubicin (DOX) carrier to compromise tumor endothelial cells, enhance BBB transportation, and improve drug accumulation in glioma cells. The drug delivery system was constructed with polydopamine (PDA)-coated mesoporous silica nanoparticles (NPs, MSNs) and the PDA coating was functionalized with Asn Gly-Arg (NGR), a ligand with specific affinity for cluster of differentiation 13 (CD13). MSN-DOX-PDA-NGR showed a higher intracellular accumulation in primary brain capillary endothelial cells (BCECs) and C6 cells and greater BBB permeability than the non-targeting NPs (MSN-DOX-PDA) did in vitro. Ex vivo and in vivo tests showed that MSN-DOX-PDA-NGR had a higher accumulation in intracranial tumorous tissue than the undecorated NPs did. Furthermore, the antiangiogenesis and antitumor efficacy of MSN-DOX-PDA-NGR were stronger than that of MSN-DOX-PDA. Therefore, these results indicate that the dual-targeting vehicles are potentially useful in brain glioma therapy. PMID- 27655665 TI - A phase I-II trial of fludarabine, bendamustine and rituximab (FBR) in previously treated patients with CLL. AB - Chemoimmunotherapy regimens have been the standard first-line therapy for patients with chronic lymphocytic leukemia (CLL). For young, fit patients the standard of care is combination of fludarabine, cyclophosphamide, and rituximab (FCR). Based on the preclinical work demonstrating that bendamustine combined with fludarabine resulted in increased DNA damage, we designed a phase I-II clinical trial with fludarabine, bendamustine, and rituximab (FBR) for patients with relapsed/refractory CLL. Treatment consisted of fludarabine 20 mg/m2 daily x 3 days and rituximab 375-500 mg/m2 x 1 day. Phase I included bendamustine at increasing doses of 20, 30, 40, or 50 mg/m2 daily x 3 days; phase II was with FR, and B at the selected dose. DNA damage response (H2AX phosphorylation) was evaluated in a subset of patients. Fifty-one patients were enrolled. The median age was 62 years; median number of prior therapies was 2; 40% had del(11q); and 41 patients had received prior FCR-based therapies. Hematologic toxicity was more common in >=40 mg/m2 dose cohorts. Maximum tolerated dose (MTD) was not identified. Bendamustine-elicited H2AX phosphorylation was not dose-dependent, but markedly increased after fludarabine. We identified bendamustine 30 mg/m2 as the safe dose for phase II. The overall response rate (ORR) was 67% with 36% complete response (CR) / CR with incomplete count recovery (CRi). Younger patients (<65 years) had significantly higher ORR (81% vs. 50%; p=0.038). The median progression-free survival was 19 months, and the median overall survival was 52.5 months. FBR is an effective and tolerable CIT regimen for patients with relapsed CLL. PMID- 27655666 TI - Smac mimetic LCL161 supports neuroblastoma chemotherapy in a drug class-dependent manner and synergistically interacts with ALK inhibitor TAE684 in cells with ALK mutation F1174L. AB - Neuroblastoma is the most common extracranial solid tumor during infancy and childhood.Outcome of high-risk and late-stage disease remains poor despite intensive treatment regimens.Suppressing inhibitor of apoptosis proteins (IAPs) using Smac mimetics (SM) significantly sensitizes neuroblastoma (NB) cells for chemotherapy, however strongly dependent on the cytotoxic drug combined with SM.Therefore, a systematic analysis of the impact of SM in combination with different classes of chemotherapeutics was of crucial importance. Treatment of NB cell lines with SM LCL161 and vinca alkaloids revealed a strong synergistic inhibition of proliferation and significant induction of apoptosis in virtually all established and de novo NB cell lines (n=8).In contrast, combination of anthracyclines or topoisomerase inhibitors with LCL161 showed a synergism for single drugs and/or cell lines only.Furthermore, we could show that insensibility to LCL161-mediated sensitization for chemotherapeutics is associated with aberrant activation of anaplastic lymphoma kinase (ALK) by common mutation F1174L. Inhibition of ALK using TAE684 is able to overcome this resistance in a synergistic fashion, a finding that could be highly relevant for improvement of neuroblastoma therapy. PMID- 27655668 TI - A model for the effects of germanium on silica biomineralization in choanoflagellates. AB - Silica biomineralization is a widespread phenomenon of major biotechnological interest. Modifying biosilica with substances like germanium (Ge) can confer useful new properties, although exposure to high levels of Ge disrupts normal biosilicification. No clear mechanism explains why this disruption occurs. Here, we study the effect of Ge on loricate choanoflagellates, a group of protists that construct a species-specific extracellular lorica from multiple siliceous costal strips. High Ge exposures were toxic, whereas lower Ge exposures produced cells with incomplete or absent loricae. These effects can be ameliorated by restoring the germanium : silicon ratio, as observed in other biosilicifying organisms. We developed simulations of how Ge interacts with polymerizing silica. In our models, Ge is readily incorporated at the ends of silica forming from silicic acid condensation, but this prevents further silica polymerization. Our 'Ge capping' model is supported by observations from loricate choanoflagellates. Ge exposure terminates costal strip synthesis and lorica formation, resulting in disruption to cytokinesis and fatal build-up of silicic acid. Applying the Ge capping model to other siliceous organisms explains the general toxicity of Ge and identifies potential protective responses in metalloid uptake and sensing. This can improve the design of new silica biomaterials, and further our understanding of silicon metabolism. PMID- 27655667 TI - Cerebellar-inspired algorithm for adaptive control of nonlinear dielectric elastomer-based artificial muscle. AB - Electroactive polymer actuators are important for soft robotics, but can be difficult to control because of compliance, creep and nonlinearities. Because biological control mechanisms have evolved to deal with such problems, we investigated whether a control scheme based on the cerebellum would be useful for controlling a nonlinear dielectric elastomer actuator, a class of artificial muscle. The cerebellum was represented by the adaptive filter model, and acted in parallel with a brainstem, an approximate inverse plant model. The recurrent connections between the two allowed for direct use of sensory error to adjust motor commands. Accurate tracking of a displacement command in the actuator's nonlinear range was achieved by either semi-linear basis functions in the cerebellar model or semi-linear functions in the brainstem corresponding to recruitment in biological muscle. In addition, allowing transfer of training between cerebellum and brainstem as has been observed in the vestibulo-ocular reflex prevented the steady increase in cerebellar output otherwise required to deal with creep. The extensibility and relative simplicity of the cerebellar based adaptive-inverse control scheme suggests that it is a plausible candidate for controlling this type of actuator. Moreover, its performance highlights important features of biological control, particularly nonlinear basis functions, recruitment and transfer of training. PMID- 27655669 TI - Using collision cones to assess biological deconfliction methods. AB - Biological systems consistently outperform autonomous systems governed by engineered algorithms in their ability to reactively avoid collisions. To better understand this discrepancy, a collision avoidance algorithm was applied to frames of digitized video trajectory data from bats, swallows and fish (Myotis velifer, Petrochelidon pyrrhonota and Danio aequipinnatus). Information available from visual cues, specifically relative position and velocity, was provided to the algorithm which used this information to define collision cones that allowed the algorithm to find a safe velocity requiring minimal deviation from the original velocity. The subset of obstacles provided to the algorithm was determined by the animal's sensing range in terms of metric and topological distance. The algorithmic calculated velocities showed good agreement with observed biological velocities, indicating that the algorithm was an informative basis for comparison with the three species and could potentially be improved for engineered applications with further study. PMID- 27655670 TI - Human and avian running on uneven ground: a model-based comparison. AB - Birds and humans are successful bipedal runners, who have individually evolved bipedalism, but the extent of the similarities and differences of their bipedal locomotion is unknown. In turn, the anatomical differences of their locomotor systems complicate direct comparisons. However, a simplifying mechanical model, such as the conservative spring-mass model, can be used to describe both avian and human running and thus, provides a way to compare the locomotor strategies that birds and humans use when running on level and uneven ground. Although humans run with significantly steeper leg angles at touchdown and stiffer legs when compared with cursorial ground birds, swing-leg adaptations (leg angle and leg length kinematics) used by birds and humans while running appear similar across all types of uneven ground. Nevertheless, owing to morphological restrictions, the crouched avian leg has a greater range of leg angle and leg length adaptations when coping with drops and downward steps than the straight human leg. On the other hand, the straight human leg seems to use leg stiffness adaptation when coping with obstacles and upward steps unlike the crouched avian leg posture. PMID- 27655671 TI - IMP1, an mRNA binding protein that reduces the metastatic potential of breast cancer in a mouse model. AB - Cells that are able to localize beta-actin mRNA efficiently have decreased metastatic potential. Invasive carcinoma cells derived from primary mammary tumors have reduced levels of an RNA binding protein IMP1/ZBP1/IGF2BP1, required for beta-actin mRNA localization. We showed previously that in human breast carcinoma cells in vitro, this protein suppresses invasion. In this work we examined whether its re-expression can suppress breast cancer metastasis in a breast cancer mouse model. We developed a mouse conditionally expressing IMP1-GFP (hereinafter referred to as the IMP1 transgene) specifically in the mammary gland of a PYMT breast cancer mouse. We found that mice conditionally expressing the IMP1 transgene showed little or no metastases to the lungs from the primary tumor in contrast to PYMT mice not expressing IMP1, which uniformly develop metastases at an early stage. PMID- 27655672 TI - Positive association of collagen type I with non-muscle invasive bladder cancer progression. AB - PURPOSE: Non-muscle invasive bladder cancers (NMIBC) are generally curable, while ~15% progresses into muscle-invasive cancer with poor prognosis. While efforts have been made to identify genetic alternations associated with progression, the extracellular matrix (ECM) microenvironment remains largely unexplored. Type I collagen is a major component of the bladder ECM, and can be altered during cancer progression. We set out to explore the association of type I collagen with NMIBC progression. EXPERIMENTAL DESIGN: The associations of COL1A1 and COL1A2 mRNA levels with progression were evaluated in a multi-center cohort of 189 patients with NMIBCs. Type I collagen protein expression and structure were evaluated in an independent single-center cohort of 80 patients with NMIBCs. Immunohistochemical analysis was performed and state-of-the-art multi-photon microscopy was used to evaluate collagen structure via second harmonic generation imaging. Progression to muscle invasion was the primary outcome. Kaplan-Meier method, Cox regression, and Wilcoxon rank-sum were used for statistical analysis. RESULTS: There is a significant association of high COL1A1 and COL1A2 mRNA expression in patients with poor progression-free survival (P=0.0037 and P=0.011, respectively) and overall survival (P=0.024 and P=0.012, respectively). Additionally, immunohistochemistry analysis of type I collagen protein deposition revealed a significant association with progression (P=0.0145); Second-harmonic generation imaging revealed a significant lower collagen fiber curvature ratio in patients with invasive progression (P = 0.0018). CONCLUSIONS: Alterations in the ECM microenvironment, particularly type I collagen, likely contributes to bladder cancer progression. These findings will open avenues to future functional studies to investigate ECM-tumor interaction as a potential therapeutic intervention to treat NMIBCs. PMID- 27655673 TI - Apoptosis signal-regulating kinase 1 exhibits oncogenic activity in pancreatic cancer. AB - Pancreatic cancer has an extremely grim prognosis, with an overall 5-year survival rate less than 5%, as a result of its rapid metastasis and late diagnosis. To combat this disease, it is crucial to better understand the molecular mechanisms that contribute to its pathogenesis. Herein, we report that apoptosis signal-regulating kinase 1 (ASK1) is overexpressed in pancreatic cancer tissues and that its expression correlates with the histological grade of pancreatic cancer. The expression of ASK1 is also elevated in pancreatic cancer cell lines at both protein and mRNA levels. In addition, ASK1 promotes the proliferation and stimulates the tumorigenic capacity of pancreatic cancer cells. These functions of ASK1 are abrogated by pharmacological inhibition of its kinase activity or by introduction of a kinase-dead mutation, suggesting that the kinase activity of ASK1 is required for its role in pancreatic cancer. However, the alteration of ASK1 expression or activity does not significantly affect the migration or invasion of pancreatic cancer cells. Collectively, these findings reveal a critical role for ASK1 in the development of pancreatic cancer and have important implications for the diagnosis and treatment of this malignancy. PMID- 27655675 TI - miR-424-5p promotes proliferation of gastric cancer by targeting Smad3 through TGF-beta signaling pathway. AB - MiRNAs have been reported to regulate gene expression and be associated with cancer progression. Recently, miR-424-5p was reported to play important role in a variety of tumors. However, the role and molecular mechanisms of miR-424-5p in GC (gastric cancer) remains largely unknown. In this study, we aimed to explore the role of miR-424-5p in GC. QRT-PCR was used to determine the expression levels of miR-424-5p and Smad3. CCK8 assay, plate clone assay and cell cycle assay were used to measure the effects of miR-424-5p on GC cell proliferation. Luciferase reporter assay and western blotting were used to prove that Smad3 was one of the direct targets of miR-424-5p. Tumorigenesis assay was used to investigate the role of miR-424-5p in tumor growth of GC cells in vivo. We found that miR-424-5p was up-regulated in GC tissues and cells. Over-expression of miR-424-5p could promote the proliferation of GC cells. In addition, luciferase reporter assay and western blotting assay revealed that Smad3 was a direct target of miR-424-5p. Over-expression of Smad3 could partially reverse the effects of miR-424-5p on GC cell proliferation. Our study further revealed that miR-424-5p could inhibit TGF beta signaling pathway by Smad3. PMID- 27655674 TI - Oxidative stress-induced epigenetic changes associated with malignant transformation of human kidney epithelial cells. AB - Renal Cell Carcinoma (RCC) in humans is positively influenced by oxidative stress status in kidneys. We recently reported that adaptive response to low level of chronic oxidative stress induces malignant transformation of immortalized human renal tubular epithelial cells. Epigenetic alterations in human RCC are well documented, but its role in oxidative stress-induced malignant transformation of kidney cells is not known. Therefore, the objective of this study was to evaluate the potential role of epigenetic changes in chronic oxidative stress-induced malignant transformation of HK-2, human renal tubular epithelial cells. The results revealed aberrant expression of epigenetic regulatory genes involved in DNA methylation (DNMT1, DNMT3a and MBD4) and histone modifications (HDAC1, HMT1 and HAT1) in HK-2 cells malignantly transformed by chronic oxidative stress. Additionally, both in vitro soft agar assay and in vivo nude mice study showing decreased tumorigenic potential of malignantly transformed HK-2 cells following treatment with DNA de-methylating agent 5-aza 2' dC further confirmed the crucial role of DNA hypermethyaltion in oxidative stress-induced malignant transformation. Changes observed in global histone H3 acetylation (H3K9, H3K18, H3K27 and H3K14) and decrease in phospho-H2AX (Ser139) also suggest potential role of histone modifications in increased survival and malignant transformation of HK-2 cells by oxidative stress. In summary, the results of this study suggest that epigenetic reprogramming induced by low levels of oxidative stress act as driver for malignant transformation of kidney epithelial cells. Findings of this study are highly relevant in potential clinical application of epigenetic-based therapeutics for treatments of kidney cancers. PMID- 27655676 TI - Endotoxin promotes neutrophil hierarchical chemotaxis via the p38-membrane receptor pathway. AB - Neutrophils are the most abundant leukocytes in peripheral blood and play critical a role in bacterial infection, tumor immunity and wound repair. Clarifying the process of neutrophil chemotaxis to target sites of immune activity has been a focus of increased interest within the past decade. In bacterial infectious foci, neutrophils migrate toward the bacterial-derived chemoattractant N-formyl-Met-Leu-Phe (fMLP) and ignore other intermediary chemoattractants to arrive at the area of infection. Using an under agarose chemotaxis assay, we observed that the bacterial fMLP-induced neutrophil chemotaxis signal overrode interleukin 8 (IL-8)- and leukotriene B4 (LTB4) induced chemotaxis signals. Moreover, in the presence of bacterial lipopolysaccharide (LPS), the fMLP-induced hierarchical chemotaxis signal was enhanced. Further studies revealed that LPS increased the membrane expression of the fMLP receptor, formyl peptide receptor 1 (FPR1). However, expression levels of the membrane receptors for IL-8 and LTB4 were decreased by LPS administration. A human Phospho-mitogen-activated protein kinase (MAPK) proteome array showed that the p38 pathway was significantly activated by LPS stimulation. Moreover, p38 was responsible for the altered expression of neutrophil membrane chemoattractant receptors. Inhibition of neutrophil p38 restored LPS-improved hierarchical chemotaxis. Taken together, these data indicate that endotoxin promotes neutrophil hierarchical chemotaxis via the p38-membrane receptor pathway. PMID- 27655677 TI - The impact of neuronal Notch-1/JNK pathway on intracerebral hemorrhage-induced neuronal injury of rat model. AB - Notch signaling is a highly conserved pathway that regulates cell fate decisions during embryonic development. Notch activation endangers neurons by modulating NF kappaB and HIF-1alpha pathways, however, the role of Notch signaling in activating JNK/c-Jun following intracerebral hemorrhage (ICH) has not been investigated. In this study, we used rat ICH models and thrombin-induced cell models to investigate the potential role of Notch-1/JNK signals. Our findings revealed that Notch-1 and JNK increased in hematoma-surrounding neurons tissues following ICH during ischemic conditions (all p<0.05). Besides, the expression of active caspase-3 protein was also up-regulated after ICH. According to in-vitro assays, the expression of Notch-1, p-JNK, and active caspase-3 were all up regulated in cell viability-decreasing ICH cell models (all p<0.05). However, blocking of either Notch-1 or JNK suppressed the phosphorylation of JNK and the expression of active caspase-3, and cell viability was obviously ameliorated. In conclusion, this work suggested Notch-1 activates JNK pathway to induce the active caspase-3, leading to neuronal injury when intracerebral hemorrhage or ischemia occurred. Thus the Notch-1/JNK signal pathway has an important role in ICH process, and may be a therapeutic target to prevent brain injury. PMID- 27655678 TI - RPN13/ADRM1 inhibitor reverses immunosuppression by myeloid-derived suppressor cells. AB - Myeloid-derived-suppressor cells (MDSCs) are key mediators of immune suppression in the ovarian tumor microenvironment. Modulation of MDSC function to relieve immunosuppression may enhance the immunologic clearance of tumors. The bis benzylidine piperidone RA190 binds to the ubiquitin receptor RPN13/ADRM1 on the 19S regulatory particle of the proteasome and directly kills ovarian cancer cells by triggering proteotoxic stress. Here we examine the effect of RA190 treatment on the immunosuppression induced by MDSCs in the tumor microenvironment, specifically on the immunosuppression induced by MDSCs. We show that RA190 reduces the expression of Stat3 and the levels of key immunosuppressive enzymes and cytokines arginase, iNOS, and IL-10 in MDSCs, while boosting expression of the immunostimulatory cytokine IL-12. Furthermore, we show that the RA190-treated MDSCs lost their capacity to suppress CD8+ T cell function. Finally, we show that RA190 treatment of mice bearing syngeneic ovarian tumor elicits potent CD8+ T cell antitumor immune responses and improves tumor control and survival. These data suggest the potential of RA190 for ovarian cancer treatment by both direct killing of tumor cells via proteasome inhibition and relief of MDSC-mediated suppression of CD8 T cell-dependent antitumor immunity elicited by the apoptotic tumor cells. PMID- 27655679 TI - Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma. AB - BACKGROUND: Immunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored. RESULTS: NY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings. CONCLUSIONS: We found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy. PMID- 27655680 TI - NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma. AB - Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is not typical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been poorly studied in patients with B-CLL/SLL. Here we report for the first time the NK cell phenotype and function in patients with B-CLL and SLL alongside their transcriptional profile. We show for the first time impaired B-CLL NK cell function in a xenograft model with reduced activating receptor expression including NKG2D, DNAM-1 and NCRs in-vitro. Importantly, we show these functional differences are associated with transcriptional downregulation of cytotoxic pathway genes, including activating receptors, adhesion molecules, cytotoxic molecules and intracellular signalling molecules, which remain intact in patients with SLL. In conclusion, NK cell function is markedly influenced by the anatomical site of the tumor in patients with B-CLL/SLL and lymphocytosis leads to marked impairment of NK cell activity. These observations have implications for treatment protocols which seek to preserve immune function by limiting the exposure of NK cells to tumor cells within the peripheral circulation. PMID- 27655681 TI - Blood RNA expression profiles undergo major changes during the seventh decade. AB - Genome-wide alterations in RNA expression profiles are age-associated. Yet the rate and temporal pattern of those alterations are poorly understood. We investigated temporal changes in RNA expression profiles in blood from population based studies using a quadratic regression model. Comparative analysis between two independent studies was carried out after sample-weighting that downsized differences in sample distribution over age between the datasets. We show that age-associated expression profiles are clustered into two major inclinations and transcriptional alternations occur predominantly from the seventh decade onwards. The age-associated genes in blood are enriched in functional groups of the translational machinery and the immune system. The results are highly consistent between the two population-based studies indicating that our analysis overcomes potential confounders in population-based studies. We suggest that the critical age when major transcriptional alterations occur could help understanding aging and disease risk during adulthood. PMID- 27655682 TI - A rational approach for cancer stem-like cell isolation and characterization using CD44 and prominin-1(CD133) as selection markers. AB - The availability of adequate cancer stem cells or cancer stem-like cell (CSC) is important in cancer study. From ovarian cancer cell lines, SKOV3 and OVCAR3, we induced peritoneal ascites tumors in immunodeficient mice. Among the cells (SKOV3.PX1 and OVCAR3.PX1) from those tumors, we sorted both CD44 and CD133 positive cells (SKOV3.PX1_133+44+, OVCAR3.PX1_133+44+), which manifest the characteristics of self-renewal, multi-lineage differentiation, chemoresistance and tumorigenicity, those of cancer stem-like cells (CSLC). Intraperitoneal transplantation of these CD44 and CD133 positive cells resulted in poorer survival in the engrafted animals. Clinically, increased CD133 expression was found in moderately and poorly differentiated (grade II and III) ovarian serous cystadenocarcinomas. The ascites tumor cells from human ovarian cancers demonstrated more CD133 and CD44 expressions than those from primary ovarian or metastatic tumors and confer tumorigenicity in immunodeficient mice. Compared to their parental cells, the SKOV3.PX1_133+44+ and OVCAR3.PX1_133+44+ cells uniquely expressed 5 CD markers (CD97, CD104, CD107a, CD121a, and CD125). Among these markers, CD97, CD104, CD107a, and CD121a are significantly more expressed in the CD133+ and CD44+ double positive cells of human ovarian ascites tumor cells (Ascites_133+44+) than those from primary ovarian or metastatic tumors. The cancer stem-like cells were enriched from 3% to more than 70% after this manipulation. This intraperitoneal enrichment of cancer stem-like cells, from ovarian cancer cell lines or primary ovarian tumor, potentially provides an adequate amount of ovarian cancer stem-like cells for the ovarian cancer study and possibly benefits cancer therapy. PMID- 27655683 TI - Liver regeneration microenvironment of hepatocellular carcinoma for prevention and therapy. AB - Research on liver cancer prevention and treatment has mainly focused on the liver cancer cells themselves. Currently, liver cancers are no longer viewed as only collections of genetically altered cells but as aberrant organs with a plastic stroma, matrix, and vasculature. Improving the microenvironment of the liver to promote liver regeneration and repair by affecting immune function, inflammation and vasculature can regulate the dynamic imbalance between normal liver regeneration and repair and abnormal liver regeneration, thus improving the microenvironment of liver regeneration for the prevention and treatment of liver cancer. This review addresses the basic theory of the liver regeneration microenvironment, including the latest findings on immunity, inflammation and vasculature. Attention is given to the potential design of molecular targets in the microenvironment of hepatocellular carcinoma (HCC). In an effort to improve the liver regeneration microenvironment of HCC, researchers have extensively utilized the enhancement of immunity, anti-inflammation and the vasculature niche, which are discussed in detail in this review. In addition, the authors summarize the latest pro-fibrotic transition characteristics of the vascular niche and review potential cell therapies for liver disease. PMID- 27655684 TI - Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding. AB - Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase transmembrane receptor that has also a soluble isoform containing most of the extracellular ligand binding domain (sVEGFR-1). VEGF-A binds to both VEGFR-2 and VEGFR-1, whereas placenta growth factor (PlGF) interacts exclusively with VEGFR 1. In this study we generated an anti-VEGFR-1 mAb (D16F7) by immunizing BALB/C mice with a peptide that we had previously reported to inhibit angiogenesis and endothelial cell migration induced by PlGF. D16F7 did not affect binding of VEGF A or PlGF to VEGFR-1, thus allowing sVEGFR-1 to act as decoy receptor for these growth factors, but it hampered receptor homodimerization and activation. D16F7 inhibited both the chemotactic response of human endothelial, myelomonocytic and melanoma cells to VEGFR-1 ligands and vasculogenic mimicry by tumor cells. Moreover, D16F7 exerted in vivo antiangiogenic effects in a matrigel plug assay. Importantly, D16F7 inhibited tumor growth and was well tolerated by B6D2F1 mice injected with syngeneic B16F10 melanoma cells. The antitumor effect was associated with melanoma cell apoptosis, vascular abnormalities and decrease of both monocyte/macrophage infiltration and myeloid progenitor mobilization. For all the above, D16F7 may be exploited in the therapy of metastatic melanoma and other tumors or pathological conditions involving VEGFR-1 activation. PMID- 27655685 TI - Dormant tumor cells expressing LOXL2 acquire a stem-like phenotype mediating their transition to proliferative growth. AB - Recurrence of breast cancer disease years after treatment appears to arise from disseminated dormant tumor cells (DTC). The mechanisms underlying the outgrowth of DTC remain largely unknown. Here we demonstrate that dormant MCF-7 cells expressing LOXL2 acquire a cancer stem cell (CSC)-like phenotype, mediating their outgrowth in the 3D BME system that models tumor dormancy and outgrowth. Similarly, MCF-7-LOXL2 cells colonizing the lung transitioned from dormancy to metastatic outgrowth whereas MCF-7 cells remained dormant. Notably, epithelial to mesenchymal transition (EMT) of MCF-7-LOXL2 cells was required for their CSC-like properties and their transition to metastatic outgrowth. These findings were further supported by clinical data demonstrating that increase in LOXL2 mRNA levels correlates with increase in the mRNA levels of EMT and stem cells markers, and is also associated with decrease in relapse free survival of breast cancer patients. Notably, conditional hypoxia induced expression of endogenous LOXL2 in MCF-7 cells promoted EMT and the acquisition of a CSC-like phenotype, while knockdown of LOXL2 inhibited this transition. Overall, our results demonstrate that expression of LOXL2 endowed DTC with CSC-like phenotype driving their transition to metastatic outgrowth and this stem-like phenotype is dependent on EMT that can be driven by the tumor microenvironment. PMID- 27655686 TI - Targeting p53-deficient chronic lymphocytic leukemia cells in vitro and in vivo by ROS-mediated mechanism. AB - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Loss of p53 function in CLL cells due to chromosome 17p deletion or p53 mutations often leads to a more malignant disease phenotype and is associated with drug resistance and poor clinical outcome. Thus, development of novel therapeutic strategies to effectively target CLL cells with p53 deficiency is clinically important. Here we showed that p53-null CLL cells were highly sensitive to ROS-mediated cell killing due to their intrinsic ROS stress. We further demonstrated that a natural compound phenethyl isothiocyanate (PEITC) was able to effectively kill CLL cells with loss of p53, even under the protection of stromal cells. In p53-defficient CLL cells, PEITC induced a rapid depletion of glutathione and a severe accumulation of ROS, leading to massive leukemia cell death in the stromal microenvironment. The drug-induced cell death was associated with a significant decrease of in MCL-1 survival molecule. We further showed that ROS-mediated cell death was the key mechanism by which PEITC induced cytotoxicity, since such cell death could be prevented by addition of antioxidant NAC. Importantly, in vivo study showed that PEITC was able to induce substantial leukemia cell death in mice. Treatment of CLL mice harboring TCL1-Tg:p53-/- genotype with PEITC significantly prolonged the median survival time of the animals. Our study identifies a vulnerability of p53-null CLL cells with high sensitivity to ROS-generating agents, and suggests that PEITC may potentially be useful for clinical treatment of CLL with 17p deletion and p53 mutations. PMID- 27655687 TI - X-radiation enhances the collagen type I strap formation and migration potentials of colon cancer cells. AB - Rectal cancer treatment still fails with local and distant relapses of the disease. It is hypothesized that radiotherapy could stimulate cancer cell dissemination and metastasis. In this study, we evaluated the effect of X radiation on collagen type I strap formation potential, i.e. matrix remodeling associated with mesenchymal cell migration, and behaviors of SW480, SW620, HCT116 p53+/+ and HCT116 p53-/- colon cancer cells. We determined a radiation-induced increase in collagen type I strap formation and migration potentials of SW480 and HCT116 p53+/+. Further studies with HCT116 p53+/+, indicated that after X radiation strap forming cells have an increased motility. More, we detected a decrease in adhesion potential and mature integrin beta1 expression, but no change in non-muscle myosin II expression for HCT116 p53+/+ after X-radiation. Integrin beta1 neutralization resulted in a decreased cell adhesion and collagen type I strap formation in both sham and X-radiated conditions. Our study indicates collagen type I strap formation as a potential mechanism of colon cancer cells with increased migration potential after X-radiation, and suggests that other molecules than integrin beta1 and non-muscle myosin II are responsible for the radiation-induced collagen type I strap formation potential of colon cancer cells. This work encourages further molecular investigation of radiation induced migration to improve rectal cancer treatment outcome. PMID- 27655689 TI - Receptor conversion in metastatic breast cancer: a prognosticator of survival. AB - OBJECTIVE: This retrospective study investigated the association between hormone receptor (HR) conversion and survival in breast cancer patients. METHODS: Estrogen receptor (ER) and progesterone receptor (PR) status (positive or negative) of primary tumors and of paired metastatic sites in 627 breast cancer patients were analyzed by McNemar's test for rates of receptor conversion. A survival analysis was performed using the Kaplan-Meier method, and prognostic factors were assessed using Cox's proportional hazards regression model. RESULTS: Conversion of ER occurred in 165 (26.31%) patients, and conversion of PR in 213 (33.97%; P < 0.001, both). For 82 patients whose ER and PR were reassessed 2-4 times during metastatic progression, ER and PR re-conversion occurred in 22 (26.83%) and 29 (35.36%), respectively. The change of ER or PR from positive to negative was associated with worse overall survival and post-recurrent survival (log-rank; P < 0.001, both). A subgroup analysis of HR-positive patients (i.e., positive ER, PR, or both) in primary tumor and HR-negative in metastatic sites showed that patients who accepted both salvage endocrine therapy and chemotherapy had better post-recurrent survival than did those who accepted salvage chemotherapy only (log-rank; P = 0.003). CONCLUSION: ER and PR status may change several times during metastatic tumor progression. A change of HR from positive to negative was associated with worse survival compared with consistent positivity. Repeated evaluations of HR status are necessary in metastatic breast cancer. Salvage hormonal therapy is still worth trying for patients whose HR status changes from positive to negative. PMID- 27655688 TI - Elevated level of acetylation of APE1 in tumor cells modulates DNA damage repair. AB - Apurinic/apyrimidinic (AP) sites are frequently generated in the genome by spontaneous depurination/depyrimidination or after removal of oxidized/modified bases by DNA glycosylases during the base excision repair (BER) pathway. Unrepaired AP sites are mutagenic and block DNA replication and transcription. The primary enzyme to repair AP sites in mammalian cells is AP endonuclease (APE1), which plays a key role in this repair pathway. Although overexpression of APE1 in diverse cancer types and its association with chemotherapeutic resistance are well documented, alteration of posttranslational modification of APE1 and modulation of its functions during tumorigenesis are largely unknown. Here, we show that both classical histone deacetylase HDAC1 and NAD+-dependent deacetylase SIRT1 regulate acetylation level of APE1 and acetylation of APE1 enhances its AP endonuclease activity both in vitro and in cells. Modulation of APE1 acetylation level in cells alters AP site repair capacity of the cell extracts in vitro. Primary tumor tissues of diverse cancer types have higher level of acetylated APE1 (AcAPE1) compared to adjacent non-tumor tissue and exhibit enhanced AP site repair capacity. Importantly, in the absence of APE1 acetylation, cells accumulate AP sites in the genome and show increased sensitivity to DNA damaging agents. Together, our study demonstrates that elevation of acetylation level of APE1 in tumor could be a novel mechanism by which cells handle the elevated levels of DNA damages in response to genotoxic stress and maintain sustained proliferation. PMID- 27655690 TI - MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells. AB - Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p<0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p<0.001; Int-2+High, p=0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT alpha+beta- splice variant expression (p<0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression. PMID- 27655692 TI - Serum depletion induced cancer stem cell-like phenotype due to nitric oxide synthesis in oncogenic HRas transformed cells. AB - Cancer cells rewire their metabolism and mitochondrial oxidative phosphorylation (OXPHOS) to promote proliferation and maintenance. Cancer cells use multiple adaptive mechanisms in response to a hypo-nutrient environment. However, little is known about how cancer mitochondria are involved in the ability of these cells to adapt to a hypo-nutrient environment. Oncogenic HRas leads to suppression of the mitochondrial oxygen consumption rate (OCR), but oxygen consumption is essential for tumorigenesis. We found that in oncogenic HRas transformed cells, serum depletion reversibly increased the OCR and membrane potential. Serum depletion promoted a cancer stem cell (CSC)-like phenotype, indicated by an increase in CSC markers expression and resistance to anticancer agents. We also found that nitric oxide (NO) synthesis was significantly induced after serum depletion and that NO donors modified the OCR. An NOS inhibitor, SEITU, inhibited the OCR and CSC gene expression. It also reduced anchorage-independent growth by promoting apoptosis. In summary, our data provide new molecular findings that serum depletion induces NO synthesis and promotes mitochondrial OXPHOS, leading to tumor progression and a CSC phenotype. These results suggest that mitochondrial OCR inhibitors can be used as therapy against CSC. PMID- 27655691 TI - Protein tyrosine phosphatase PTP4A1 promotes proliferation and epithelial mesenchymal transition in intrahepatic cholangiocarcinoma via the PI3K/AKT pathway. AB - The protein tyrosine phosphatase PTP4A1 is a key molecule that activates tyrosine phosphorylation, which is important for cancer progression and metastasis. However, the clinical implications and biological function of PTP4A1 in intrahepatic cholangiocarcinoma (ICC) remains unknown. Here, we showed that PTP4A1 was frequently overexpressed in ICC versus adjacent non-tumor tissues. This overexpression significantly correlated with aggressive tumor characteristics like the presence of lymph node metastasis and advanced tumor stages. Survival analysis further indicated that high PTP4A1 expression was significantly and independently associated with worse survival and increased recurrence in ICC patients. Moreover, through forced overexpression and knock down of PTPT4A1, we demonstrated that PTP4A1 could significantly promote ICC cells proliferation, colony formation, migration, and invasion in vitro, and markedly enhance tumor progression in vivo. Mechanistically, PTP4A1 was involved in PI3K/AKT signaling and its downstream molecules, such as phosphorylation level of GSK3beta and up-regulation of CyclinD1, in ICC cells to promote proliferation. Importantly, PTP4A1 induced ICC cells invasion was through activating PI3K/AKT signaling controlled epithelial-mesenchymal transition (EMT) process by up regulating Zeb1 and Snail. Thus, PTP4A1 may serve as a potential oncogene that was a valuable prognostic biomarker and therapeutic target for ICC. PMID- 27655694 TI - Smyd2 is a Myc-regulated gene critical for MLL-AF9 induced leukemogenesis. AB - The Smyd2 protein (Set- and Mynd domain containing protein 2) is a methyl transferase that can modify both histones and cytoplasmic proteins. Smyd2 is over expressed in several cancer types and was shown to be limiting for tumor development in the pancreas. However, genetic evidence for a role of Smyd2 in other cancers or in mouse development was missing to date. Using germ line deleted mouse strains, we now show that Smyd2 and the related protein Smyd3 are dispensable for normal development. Ablation of Smyd2 did not affect hematopoiesis, but retarded the development of leukemia promoted by MLL-AF9, a fusion oncogene associated with acute myeloid leukemia (AML) in humans. Smyd2 deleted leukemic cells showed a competitive disadvantage relative to wild-type cells, either in vitro or in vivo. The Smyd2 gene was directly activated by the oncogenic transcription factor Myc in either MLL9-AF9-induced leukemias, Myc induced lymphomas, or fibroblasts. However, unlike leukemias, the development of lymphomas was not dependent upon Smyd2. Our data indicate that Smyd2 has a critical role downstream of Myc in AML. PMID- 27655695 TI - Cyanidin-3-o-glucoside directly binds to ERalpha36 and inhibits EGFR-positive triple-negative breast cancer. AB - Anthocyanins have been shown to inhibit the growth and metastatic potential of breast cancer (BC) cells. However, the effects of individual anthocyanins on triple-negative breast cancer (TNBC) have not yet been studied. In this study, we found that cyanidin-3-o-glucoside (Cy-3-glu) preferentially promotes the apoptosis of TNBC cells, which co-express the estrogen receptor alpha 36 (ERalpha36) and the epidermal growth factor receptor (EGFR). We demonstrated that Cy-3-glu directly binds to the ligand-binding domain (LBD) of ERalpha36, inhibits EGFR/AKT signaling, and promotes EGFR degradation. We also confirmed the therapeutic efficacy of Cy-3-glu on TNBC in the xenograft mouse model. Our data indicates that Cy-3-glu could be a novel preventive/therapeutic agent against the TNBC co-expressed ERalpha36/EGFR. PMID- 27655696 TI - Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma. AB - Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM. Here we demonstrate how this approach identified previously validated and novel therapeutic targets. In addition we show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a novel therapeutic target in myeloma. The APC/C associates independently with two cofactors, Fzr and Cdc20, to control cell cycle progression. We found high levels of FZR1 in MM primary cells and cell lines and demonstrate that expression is further increased on adhesion to bone marrow stromal cells (BMSCs). Specific knockdown of either FZR1 or CDC20 reduced viability and induced growth arrest of MM cell lines, and resulted in accumulation of APC/CFzr substrate Topoisomerase IIalpha (TOPIIalpha) or APC/CCdc20 substrate Cyclin B. Similar effects were observed following treatment with proTAME, an inhibitor of both APC/CFzr and APC/CCdc20. Combinations of proTAME with topoisomerase inhibitors, etoposide and doxorubicin, significantly increased cell death in MM cell lines and primary cells, particularly if TOPIIalpha levels were first increased through pre treatment with proTAME. Similarly, combinations of proTAME with the microtubule inhibitor vincristine resulted in enhanced cell death. This study demonstrates the potential of targeting the APC/C and its cofactors as a therapeutic approach in MM. PMID- 27655693 TI - Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature. AB - The dependence of cancer on overexpressed c-MYC and its predisposition for polyploidy represents a double puzzle. We address this conundrum by cross-species transcription analysis of c-MYC interacting genes in polyploid vs. diploid tissues and cells, including human vs. mouse heart, mouse vs. human liver and purified 4n vs. 2n mouse decidua cells. Gene-by-gene transcriptome comparison and principal component analysis indicated that c-MYC interactants are significantly overrepresented among ploidy-associated genes. Protein interaction networks and gene module analysis revealed that the most upregulated genes relate to growth, stress response, proliferation, stemness and unicellularity, as well as to the pathways of cancer supported by MAPK and RAS coordinated pathways. A surprising feature was the up-regulation of epithelial-mesenchymal transition (EMT) modules embodied by the N-cadherin pathway and EMT regulators from SNAIL and TWIST families. Metabolic pathway analysis also revealed the EMT-linked features, such as global proteome remodeling, oxidative stress, DNA repair and Warburg-like energy metabolism. Genes associated with apoptosis, immunity, energy demand and tumour suppression were mostly down-regulated. Noteworthy, despite the association between polyploidy and ample features of cancer, polyploidy does not trigger it. Possibly it occurs because normal polyploidy does not go that far in embryonalisation and linked genome destabilisation. In general, the analysis of polyploid transcriptome explained the evolutionary relation of c-MYC and polyploidy to cancer. PMID- 27655697 TI - GADD45beta, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens. AB - Avian leukosis virus subgroup J (ALV-J) is a retroviruses that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that promote resistance to ALV-J infection in chickens, we bred ALV-J resistant and susceptible chickens (F3 generation). RNA-sequencing (RNA-Seq) of liver tissue from the ALV-J resistant and susceptible chickens identified 216 differentially expressed genes; 88 of those genes were up-regulated in the ALV-J resistant chickens (compared to the susceptible ones). We screened for significantly up-regulated genes (P < 0.01) of interest in the ALV-J resistant chickens, based on their involvement in biological signaling pathways. Functional analyses showed that overexpression of GADD45beta inhibited ALV-J replication. GADD45beta could enhance defense against ALV-J infection and may be used as a molecular marker to identify ALV-J infections. PMID- 27655698 TI - Diagnostic value of circulating miR-21: An update meta-analysis in various cancers and validation in endometrial cancer. AB - MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21's diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma. PMID- 27655700 TI - Shikonin potentiates the effect of arsenic trioxide against human hepatocellular carcinoma in vitro and in vivo. AB - Hepatocellular carcinoma (HCC) is a highly lethal malignancy mostly because of metastasis, recurrence and acquired resistance to conventional chemotherapy. Arsenic trioxide (ATO) is successfully used to treat hematological malignancies, and has been proven to trigger apoptosis in HCC cells. However, the phase II trial evaluating the efficacy and toxicity of ATO in patients with HCC showed that single-agent ATO is poorly active against HCC. Therefore, it is of great importance to develop effective chemosensitization agents to ATO. The aim of the present study was to determine whether shikonin (SHI), a natural product from the root of lithospermum erythrorhizon, could synergistically enhance the anti-HCC efficacy of ATO both in vitro and in vivo. We found that the combination of SHI and ATO exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cells and normal cells. By inducing intracellular oxidative stress, SHI potentiated ATO-induced DNA damage, followed by increased activation of endoplasmic reticulum stress. In addition, inhibition of ROS reversed the apoptosis induced by SHI and ATO, and recovered the activation of endoplasmic reticulum stress, which revealed the vital role of ROS in the synergism. Moreover, HepG2 xenograft tumor growth in nude mice was more effectively inhibited by combined treatment with SHI and ATO. These data suggest that the combination of SHI with ATO presents a promising therapeutic approach for the treatment of HCC. PMID- 27655699 TI - Sorting nexin 9 (SNX9) is not essential for development and auditory function in mice. AB - Sorting nexins are a large family of evolutionarily conserved proteins that play fundamental roles in endocytosis, endosomal sorting and signaling. As an important member of sorting nexin family, sorting nexin 9 (SNX9) has been shown to participate in coordinating actin polymerization with membrane tubulation and vesicle formation. We previously showed that SNX9 is expressed in mouse auditory hair cells and might regulate actin polymerization in those cells. To further examine the physiological role of SNX9, we generated Snx9 knockout mice using homologous recombination method. Unexpectedly, Snx9 knockout mice have normal viability and fertility, and are morphologically and behaviorally indistinguishable from control mice. Further investigation revealed that the morphology and function of auditory hair cells are not affected by Snx9 inactivation, and Snx9 knockout mice have normal hearing threshold. In conclusion, our data revealed that Snx9-deficient mice do not show defects in development as well as auditory function, suggesting that SNX9 is not essential for mice development and hearing. PMID- 27655701 TI - Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori infected p27-deficient mice. AB - OBJECTIVE: Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells. DESIGN: Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year. RESULTS: Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 (p < 0.05 vs control) whereas expression of IFN-gamma and chemokines MIP 1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3. CONCLUSIONS: Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori-infected mice. PMID- 27655702 TI - Sex chromosome loss and the pseudoautosomal region genes in hematological malignancies. AB - Cytogenetic aberrations, such as chromosomal translocations, aneuploidy, and amplifications, are frequently detected in hematological malignancies. For many of the common autosomal aberrations, the mechanisms underlying their roles in cancer development have been well-characterized. On the contrary, although loss of a sex chromosome is observed in a broad range of hematological malignancies, how it cooperates in disease development is less understood. Nevertheless, it has been postulated that tumor suppressor genes reside on the sex chromosomes. Although the X and Y sex chromosomes are highly divergent, the pseudoautosomal regions are homologous between both chromosomes. Here, we review what is currently known about the pseudoautosomal region genes in the hematological system. Additionally, we discuss implications for haploinsufficiency of critical pseudoautosomal region sex chromosome genes, driven by sex chromosome loss, in promoting hematological malignancies. Because mechanistic studies on disease development rely heavily on murine models, we also discuss the challenges and caveats of existing models, and propose alternatives for examining the involvement of pseudoautosomal region genes and loss of a sex chromosome in vivo. With the widespread detection of loss of a sex chromosome in different hematological malignances, the elucidation of the role of pseudoautosomal region genes in the development and progression of these diseases would be invaluable to the field. PMID- 27655703 TI - Prognostic factors of successful on-purpose tumor biopsies in metastatic cancer patients included in the SHIVA prospective clinical trial. AB - PURPOSE: To identify patient/tumor characteristics associated with success of biopsy in patients who received multiple lines of chemotherapy. METHODS: Patients with refractory cancer from our center, who were included in a prospective randomized phase II trial comparing targeted therapies based on molecular profile of tumors versus conventional chemotherapy, were retrospectively included in this IRB-approved study. All patients had a biopsy of a tumor lesion performed during surgery, or using CT/palpation/endoscopic guidance. A biopsy was considered successful if the neoplastic cellularity was greater than 30%. Primary lesion, size and location of biopsied lesion, on-going chemotherapy and the differential attenuation between non-enhanced and venous phase (HU) for CT-guided biopsied lesions were recorded. RESULTS: 228 patients (age=59+/-15yo; M/F=1.9) were included. One hundred and sixty biopsies (72%) of the 221 biopsies performed were successful. Prognostic factors of biopsy success were: no ongoing chemotherapy, surgical or palpation-guided biopsy, lymph nodes/soft tissue location(P <0.01). Among the 221 performed biopsies, 122 (55%) were performed using CT guidance and 82 (67%) were successful. In this subgroup, biopsied lesions located in lymph nodes/soft tissue were associated with a higher success rate while lung location was associated with failure (P <0.01). The mean differential attenuation was significantly higher in lesions with a successful biopsy (P <0.001). CONCLUSION: Success of biopsy was less frequent with CT guidance than with surgical or palpation-guided biopsy and was higher in soft tissues and lymph nodes than that in visceral metastasis. Ongoing chemotherapy decreased tumor cell content and consequently the success of the biopsy samples for molecular profiling. PMID- 27655704 TI - Poorer breast cancer survival outcomes in males than females might be attributable to tumor subtype. AB - BACKGROUND & AIMS: Substantial controversy exists regarding the differences in tumor subtypes between male breast cancer (MBC) and female breast cancer (FBC). This is the largest population-based study to compare MBC and FBC patients. METHODS: Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2012, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM) between males and females. RESULTS: In all, 181,814 BC patients (1,516 male and 180,298 female) were eligible for this study. The male patients were more likely to be black, older, and have lower histological grades, more advanced stages, larger tumors, more lymph node and distant metastases and human epidermal growth factor receptor 2 (HER2)-negative tumors (each p<0.05). A matched analysis showed that the 2-year OS was 91.2% and 93.7% and that the BCSM was 2.2% and 2.5% for male and female patients, respectively. The univariate analysis showed that male triple-negative (TN), hormone receptor (HoR)-positive/HER2-positive and HoR positive/HER2-negative patients had poorer OS (p <0.01). Meanwhile, the HoR positive/HER2-positive and TN subtypes were associated with a higher BCSM in MBC patients (p<0.01). The multivariate analysis revealed that TN MBC patients had poorer OS and BCSM (p<0.05). Simultaneously, the results showed that male patients in the HoR-positive/HER2-negative subgroup were less likely to die of BC when adjusting for other factors (p<0.05). CONCLUSIONS: The analysis of 2-year OS and BCSM among the BC subtypes showed clear differences between MBC and FBC patients with the TN subtype; these differences warrant further investigation. PMID- 27655705 TI - The role of cerebral blood flow gradient in peritumoral edema for differentiation of glioblastomas from solitary metastatic lesions. AB - OBJECTIVE: Differentiation of glioblastomas from solitary brain metastases using conventional MRI remains an important unsolved problem. In this study, we introduced the conception of the cerebral blood flow (CBF) gradient in peritumoral edema-the difference in CBF values from the proximity of the enhancing tumor to the normal-appearing white matter, and investigated the contribution of perfusion metrics on the discrimination of glioblastoma from a metastatic lesion. MATERIALS AND METHODS: Fifty-two consecutive patients with glioblastoma or a solitary metastatic lesion underwent three-dimensional arterial spin labeling (3D-ASL) before surgical resection. The CBF values were measured in the peritumoral edema (near: G1; Intermediate: G2; Far: G3). The CBF gradient was calculated as the subtractions CBFG1 -CBFG3, CBFG1 - CBFG2 and CBFG2 - CBFG3. A receiver operating characteristic (ROC) curve analysis was used to seek for the best cutoff value permitting discrimination between these two tumors. RESULTS: The absolute/related CBF values and the CBF gradient in the peritumoral regions of glioblastomas were significantly higher than those in metastases(P < 0.038). ROC curve analysis reveals, a cutoff value of 1.92 ml/100g for the CBF gradient of CBFG1 -CBFG3 generated the best combination of sensitivity (92.86%) and specificity (100.00%) for distinguishing between a glioblastoma and metastasis. CONCLUSION: The CBF gradient in peritumoral edema appears to be a more promising ASL perfusion metrics in differentiating high grade glioma from a solitary metastasis. PMID- 27655706 TI - The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma. AB - GV1001 is a telomerase-based cancer vaccine made of a 16-mer telomerase reverse transcriptase (TERT) peptide, and human TERT, the rate-limiting subunit of the telomerase complex, is an attractive target for cancer vaccination. The aim of this study was to evaluate the effect of telomerase peptide vaccination, GV1001 combined with gemcitabine in treatment of pancreatic ductal adenocardinoma (PDAC). Human PDAC cell lines were used in vitro experiment and also, PDAC xenograft mice model was established using PANC1, AsPC1 and CD133+ AsPC1 (PDAC stem cell). Treatment groups were divided as follows; control, gemcitabine, GV1001, gemcitabine and GV1001 combination. The inflammatory cytokines were measured from the blood, and xenograft tumor specimens were evaluated. GV1001 treatment alone did not affect the proliferation or the apoptosis of PDAC cells. Gemcitabine alone and gemcitabine with GV1001 groups had significantly reduced in tumor size and showed abundant apoptosis compared to other treatment groups. Surprisingly, xenograft PDAC tumor specimens of gemcitabine alone group had been replaced by severe fibrosis whereas gemcitabine with GV1001 group had significantly less fibrosis. Blood levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta increased in gemcitabine alone group, however, it was decreased in gemcitabine with GV1001 group. GV1001 combined with gemcitabine treatment showed significant loss of fibrosis in tumor tissue as well as tumor cell death. Therefore, further investigation of GV1001 effect combined with gemcitabine treatment may give us useful insights to overcome the hurdle in anti cancer drug delivery over massive fibrosis around PDACs. PMID- 27655707 TI - The clinicopathologic relevance and prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy. AB - The clinicopathologic relevance and prognostic value of tumor deposits in colorectal cancer has been widely demonstrated. However, there are still debates in the prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy. In this study, rectal cancer with preoperative radiotherapy followed by resection of primary tumors registered in Surveillance, Epidemiology and End Results (SEER) database from 2010-2012 were analyzed. There were 4,813 cases eligible for this study, and tumor deposits were found in 514 (10.7%) cases. The presence of tumor deposits was significantly associated with some aggressive characteristics, including poorer tumor differentiation, more advanced ypT category, ypN category and ypTNM stage, distant metastasis, elevated carcinoembryonic antigen, higher positive rates of circumferential resection margin and perineural invasion (all P < = 0.001). Tumor deposit was also an independent negative prognostic factor for cancer-specific survival in rectal cancer with preoperative radiotherapy (adjusted HR and 95% CI: 2.25 (1.51 - 3.35)). N1c category had significant worse survival compared with N0 category (adjusted HR and 95% CI: 2.41 (1.24 - 4.69)). In conclusion, tumor deposit was a significant and independent prognostic factor, and the N1c category by the 7th edition of AJCC/TNM staging system was applicable in rectal cancer with preoperative radiotherapy. PMID- 27655709 TI - Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells. AB - Multiple myeloma (MM) is a malignant disorder of plasma cells characterized by active production and secretion of monoclonal immunoglobulins (IgG), thus rendering cells prone to endoplasmic reticulum (ER) stress. For this reason, MM cell survival requires to maintain ER homeostasis at basal levels. Deptor is an mTOR binding protein, belonging to the mTORC1 and mTORC2 complexes. It was reported that Deptor is overexpressed in MM cells where it inhibits mTOR kinase activity and promotes cell survival by activating Akt signaling. Here we identify Deptor as a nuclear protein, able to bind DNA and regulate transcription in MM cells. In particular, we found that Deptor plays an important role in the maintenance of the ER network, sustaining the expression of several genes involved in this pathway. In agreement with this, Deptor depletion induces ER stress and synergizes the effect of the proteasome inhibitor bortezomib (Bz) in MM cells. These findings provide important new insights in the ER stress control in MM cells. PMID- 27655708 TI - Clinical benefit from EGFR-TKI plus ginsenoside Rg3 in patients with advanced non small cell lung cancer harboring EGFR active mutation. AB - PURPOSE: Acquired resistance is a bottleneck that restricts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for lung cancer. Ginsenoside Rg3 is an antiangiogenic agent which can down-regulate the expressions of vascular endothelial growth factor (VEGF) and EGFR. Combination of EGFR-TKI and ginsenoside Rg3 may be a promising strategy to delay acquired resistance. This retrospective study explored the efficacy and safety of this combined regimen in patients with EGFR mutation and advanced non-small cell lung cancer (NSCLC). RESULTS: By the deadline of March 31th 2016, the median follow-up period reached 22.9 months. The median PFS was significantly longer in group A than in group B (12.4 months vs 9.9 months, P = 0.017). In addition, ORR was significantly higher in group A than in group B (59.6% vs 41.7%, P = 0.049). The median OS in group A showed no extended tendency compared with that in group B (25.4 months vs 21.4 months, P = 0.258). No significant difference in side effects was found between the two groups. METHODS: A total of 124 patients with advanced NSCLC and EGFR active mutation were collected and analyzed. All of them were treated with first-line EGFR-TKI and divided into two groups. In group A (n=52), patients were administered EGFR-TKI plus ginsenoside Rg3 at standard doses. In group B (n=72), patients received EGFR-TKI alone. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and side effects were analyzed. CONCLUSIONS: Ginsenoside Rg3 improves median PFS and ORR of first-line EGFR-TKI treatment in EGFR-mutant advanced NSCLC patients, thus providing a new regimen to delay acquired resistance of EGFR-TKI. PMID- 27655710 TI - TERT rs2853676 polymorphisms correlate with glioma prognosis in Chinese population. AB - High rates of recurrence and the lack of effective treatments contribute to the poor prognosis of patients with glioma. There is therefore an urgent need for an easily detectable biomarker to facilitate early detection. In this study, we explored the association between TERT rs2853676 genetic polymorphisms and the prognosis of Chinese glioma patients. A total of 481 glioma patients at the Tangdu Hospital of the Fourth Military Medical University in China were included in this study. The overall survival rates were calculated using the Kaplan-Meier method. Prognostic factors were determined through multivariate Cox regression analysis. The overall survival (OS) rates of one, two, and three years were 31%, 10.3%, and 7.5%, respectively. The progress-free survival (PFS) rates of one, two, and three years were 15.7%, 7.3%, and 4.7%, respectively. The genotype "A/G" of TERT rs2857676 decreased the PFS rate (hazard ratios [HR] = 0.824; P = 0.059). The genotype "A/G (HR = 0.803; 95% CI, 0.656 - 0.982; P = 0.032)" and "A/A + A/G" decreased the recurrence rate compared to the genotype G/G (HR = 0.818; 95% CI, 0.675-0.99; P = 0.040). Our study indicates that TERT rs2853676 polymorphisms correlate with glioma survival and recurrence rates in a Chinese population, which suggests that they could potentially serve as prognostic markers in glioma patients. PMID- 27655712 TI - Evaluating clinical and prognostic implications of Glypican-3 in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. In patients with HCC, histopathogical differentiation is an important indicator of prognosis; however, because determination of HCC differentiation is difficult, the recently described immunohistochemical (IHC) marker glypican3 (GPC3) might assist in HCC prognostication.The goal of our study was to investigate GPC3's IHC staining pattern and define the relationship between its expression and patients' clinicopathologic features and overall survival. We retrieved clinical parameters from 101 pathologically diagnosed HCC patients' medical records and classified these patients into 4 clinical score categories (0-3) based on increasing GPC3 staining intensity and the percentage of stained tumor cells in their resection and biopsy specimens. Histopathological samples were well, moderately, and poorly differentiated in 33, 22, and 12 patients, respectively, and the GPC3 expression rate was 63%, 86%, and 92%,respectively. The median overall survival was 49.9 months (confidence interval (CI): 35.3-64.6 months) for clinical scores 0-1 and 30.7 months (CI: 19.4-41.9 months) for clinical scores 2-3. This difference was not statistically significant (P = .06) but showed a strong trend. In conclusion, a greater GPC3 expression is associated with a worse HCC prognosis and may be a promising prognostic marker. PMID- 27655711 TI - Targeting MET and EGFR crosstalk signaling in triple-negative breast cancers. AB - There is a vital need for improved therapeutic strategies that are effective in both primary and metastatic triple-negative breast cancer (TNBC). Current treatment options for TNBC patients are restricted to chemotherapy; however tyrosine kinases are promising druggable targets due to their high expression in multiple TNBC subtypes. Since coexpression of receptor tyrosine kinases (RTKs) can promote signaling crosstalk and cell survival in the presence of kinase inhibitors, it is likely that multiple RTKs will need to be inhibited to enhance therapeutic benefit and prevent resistance. The MET and EGFR receptors are actionable targets due to their high expression in TNBC; however crosstalk between MET and EGFR has been implicated in therapeutic resistance to single agent use of MET or EGFR inhibitors in several cancer types. Therefore it is likely that dual inhibition of MET and EGFR is required to prevent crosstalk signaling and acquired resistance. In this study, we evaluated the heterogeneity of MET and EGFR expression and activation in primary and metastatic TNBC tumorgrafts and determined the efficacy of MET (MGCD265 or crizotinib) and/or EGFR (erlotinib) inhibition against TNBC progression. Here we demonstrate that combined MET and EGFR inhibition with either MGCD265 and erlotinib treatment or crizotinib and erlotinib treatment were highly effective at abrogating tumor growth and significantly decreased the variability in treatment response compared to monotherapy. These results advance our understanding of the RTK signaling architecture in TNBC and demonstrate that combined MET and EGFR inhibition may be a promising therapeutic strategy for TNBC patients. PMID- 27655713 TI - SMAD4 loss enables EGF, TGFbeta1 and S100A8/A9 induced activation of critical pathways to invasion in human pancreatic adenocarcinoma cells. AB - Epidermal Growth Factor (EGF) receptor overexpression, KRAS, TP53, CDKN2A and SMAD4 mutations characterize pancreatic ductal adenocarcinoma. This mutational landscape might influence cancer cells response to EGF, Transforming Growth Factor beta1 (TGFbeta1) and stromal inflammatory calcium binding proteins S100A8/A9. We investigated whether chronic exposure to EGF modifies in a SMAD4 dependent manner pancreatic cancer cell signalling, proliferation and invasion in response to EGF, TGFbeta1 and S100A8/A9. BxPC3, homozigously deleted (HD) for SMAD4, and BxPC3-SMAD4+ cells were or not stimulated with EGF (100 ng/mL) for three days. EGF pre-treated and non pretreated cells were stimulated with a single dose of EGF (100 ng/mL), TGFbeta1 (0,02 ng/mL), S100A8/A9 (10 nM). Signalling pathways (Reverse Phase Protein Array and western blot), cell migration (Matrigel) and cell proliferation (XTT) were evaluated. SMAD4 HD constitutively activated ERK and Wnt/beta-catenin, while inhibiting PI3K/AKT pathways. These effects were antagonized by chronic EGF, which increased p-BAD (anti-apoptotic) in response to combined TGFbeta1 and S100A8/A9 stimulation. SMAD4 HD underlied the inhibition of NF-kappaB and PI3K/AKT in response to TGFbeta1 and S100A8/A9, which also induced cell migration. Chronic EGF exposure enhanced cell migration of both BxPC3 and BxPC3-SMAD4+, rendering the cells less sensitive to the other inflammatory stimuli. In conclusion, SMAD4 HD is associated with the constitutive activation of the ERK and Wnt/beta-catenin signalling pathways, and favors the EGF-induced activation of multiple signalling pathways critical to cancer proliferation and invasion. TGFbeta1 and S100A8/A9 mainly inhibit NF-kappaB and PI3K/AKT pathways and, when combined, sinergize with EGF in enhancing anti-apoptotic p-BAD in a SMAD4-dependent manner. PMID- 27655715 TI - A dosimetric and treatment efficiency evaluation of stereotactic body radiation therapy for peripheral lung cancer using flattening filter free beams. AB - To investigate potential dosimetric benefits and treatment efficiency of dynamic conformal arc therapy (DCA), intensity modulated radiation therapy (IMRT), and double partial arcs Rapidarc (RA) techniques in the treatment of early-stage peripheral lung cancer using stereotactic body radiotherapy (SBRT) with flattening filter free (FFF) beams. Twenty early-stage peripheral lung cancer patients were selected. For each patient, DCA, IMRT and RA plans were created to meet Radiation Therapy Oncology Group (RTOG) 0915 objectives with 48 Gy covering 95% of the planning target volume (PTV) in 4 fractions. PTV coverage, organs at risk (OARs) doses, planning time, monitor units (MU) and treatment time were evaluated. RA was significantly better than DCA for PTV coverage. RA provided a lower V32Gy to chest wall and less V20Gy to lung over those of DCA and IMRT. For other OARs, there is no significant difference among all three techniques. DCA plans showed significantly less planning time, shorter treatment time and lower MU number than those of RA and IMRT. RA provides a superior dosimetric benefit to DCA and IMRT in the treatment of early-stage lung cancer using SBRT with FFF beams. Considering the MU number, planning time and treatment efficiency, DCA technique is an effective treatment strategy. PMID- 27655714 TI - Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer. AB - Ovarian cancer is the most fatal gynecologic cancer with poor prognosis. Etiological factors underlying ovarian cancer genesis and progression are poorly understood. Previously, we have shown that JNK-associated Leucine zipper Protein (JLP), promotes oncogenic signaling. Investigating the role of JLP in ovarian cancer, our present study indicates that JLP is overexpressed in ovarian cancer tissue and ovarian cancer cells. Transient overexpression of JLP promotes proliferation and invasive migration of ovarian cancer cells. In addition, ectopic expression of JLP confers long-term survival and clonogenic potential to normal fallopian tube-derived epithelial cells. Coimmunoprecipitation and colocalization analyses demonstrate the in vivo interaction of JLP and JNK, which is stimulated by lysophosphatidic acid (LPA), an oncogenic lipid growth factor in ovarian cancer. We also show that LPA stimulates the translocation of JLP-JNK complex to the perinuclear region of SKOV3-ip cells. JLP-knockdown using shRNA abrogates LPA-stimulated activation of JNK as well as LPA-stimulated proliferation and invasive migration of SKOV3-ip cells. Studies using ovarian cancer xenograft mouse model indicate that the mice bearing JLP-silenced xenografts exhibits reduced tumor volume. Analysis of the xenograft tumor tissues indicate a reduction in the levels of JLP, JNK, phosphorylated-JNK, c-Jun and phosphorylated-c-Jun in JLP-silenced xenografts, thereby correlating the attenuated JLP-JNK signaling node with suppressed tumor growth. Thus, our results identify a critical role for JLP-signaling axis in ovarian cancer and provide evidence that targeting this signaling node could provide a new avenue for therapy. PMID- 27655716 TI - Novel lymph node ratio predicts prognosis of colorectal cancer patients after radical surgery when tumor deposits are counted as positive lymph nodes: a retrospective multicenter study. AB - The lymph node ratio (LNR), defined as the relation of tumor-infiltrated to resected lymph nodes, has been identified as an independent prognostic factor for colorectal cancer (CRC) after radical surgery. Recently, new guidelines propose counting tumor deposits (TDs) as positive lymph nodes (pLNs). The aim of this study was to investigate whether a novel LNR (nLNR) that considers TDs as pLNs can be used to accurately predict the long-term outcome of CRC patients. In this multicenter retrospective study, clinicopathological and outcome data from 2,051 stage III CRC patients who underwent R0 resection were collected between January 2004 and December 2011. Disease-free survival (DFS) and overall survival (OS) according to the nLNR category were analyzed using Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to determine significant prognostic factors, and ROC curves were computed to measure the predictive capacity of the nLNR category. The 5-year DFS rates of nLNR1-4 were 68.3%, 48.4%, 33.3% and 16.5%, respectively (P<0.0001), and the 5-year OS rate of nLNR1-4 were 71.8%, 60.1%, 42.7% and 21.8%, respectively (P<0.0001). The area of under curve (AUC) of the nLNR was 0.686 (95% CI 0.663-0.710) and 0.672 (95% CI 0.648-0.697) for predicting DFS and OS. Our results demonstrate that the nLNR predicted long term outcomes better than the LNR, npN and pN, using the cutoff points 0.250, 0.500 and 0.750. PMID- 27655717 TI - Targeting Notch enhances the efficacy of ERK inhibitors in BRAF-V600E melanoma. AB - The discovery of activating BRAF mutations in approximately 50% of melanomas has led to the development of MAPK pathway inhibitors, which have transformed melanoma therapy. However, not all BRAF-V600E melanomas respond to MAPK inhibition. Therefore, it is important to understand why tumors with the same oncogenic driver have variable responses to MAPK inhibitors. Here, we show that concurrent loss of PTEN and activation of the Notch pathway is associated with poor response to the ERK inhibitor SCH772984, and that co-inhibition of Notch and ERK decreased viability in BRAF-V600E melanomas. Additionally, patients with low PTEN and Notch activation had significantly shorter progression free survival when treated with BRAF inhibitors. Our studies provide a rationale to further develop combination strategies with Notch antagonists to maximize the efficacy of MAPK inhibition in melanoma. Our findings should prompt the evaluation of combinations co-targeting MAPK/ERK and Notch as a strategy to improve current therapies and warrant further evaluation of co-occurrence of aberrant PTEN and Notch activation as predictive markers of response to therapy. PMID- 27655718 TI - NOX4 downregulation leads to senescence of human vascular smooth muscle cells. AB - Senescence is a stress response characterized by an irreversible growth arrest and alterations in certain cell functions. It is believed that both double-strand DNA breaks (DSB) and increased ROS level are the main culprit of senescence. Excessive ROS production is also particularly important in the development of a number of cardiovascular disorders. In this context the involvement of professional ROS-producing enzymes, NADPH oxidases (NOX), was postulated. In contrary to the common knowledge, we have shown that not only increased ROS production but also diminished ROS level could be involved in the induction of senescence.Accordingly, our studies revealed that stress-induced premature senescence (SIPS) of vascular smooth muscle cells (VSMCs) induced by doxorubicin or H2O2, correlates with increased level of DSB and ROS. On the other hand, both SIPS and replicative senescence were accompanied by diminished expression of NOX4. Moreover, inhibition of NOX activity or decrease of NOX4 expression led to permanent growth arrest of VSMCs and secretion of interleukins and VEGF. Interestingly, cells undergoing senescence due to NOX4 depletion neither acquired DSB nor activated DNA damage response. Instead, transient induction of the p27, upregulation of HIF-1alpha, decreased expression of cyclin D1 and hypophosphorylated Rb was observed. Our results showed that lowering the level of ROS-producing enzyme - NOX4 oxidase below physiological level leads to cellular senescence of VSMCs which is correlated with secretion of pro-inflammatory cytokines. Thus the use of specific NOX4 inhibitors for pharmacotherapy of vascular diseases should be carefully considered. PMID- 27655719 TI - Adipocyte miR-200b/a/429 ablation in mice leads to high-fat-diet-induced obesity. AB - Growing evidence demonstrates the important role of microRNAs (miRs) in regulating adipogenesis, obesity and insulin resistance. The miR-200b/a/429 cluster has been functionally characterized in mammalian reproduction; however, the potential role of the miR-200 family in adipocytes is poorly understood. The aim of our study was to investigate the physiological function of miR-200b/a/429 in the regulation of whole-body metabolism in terms of the activities and targets of this cluster in adipocytes. We generated adipocyte-specific miR-200b/a/429 knockout (ASKO) mice using a Cre-loxP system in which Cre expression was driven by the aP2 promoter. The ASKO and wild type (WT) littermate were fed a chow diet (CD) or high-fat-diet (HFD), and changes in body composition, metabolic parameters, energy homeostasis, glucose tolerance and insulin sensitivity were analyzed. The miR-200b/a/429 putative target genes were predicted and validated via luciferase reporter assays. We found that the HFD-fed ASKO mice gradually gained more body weight than the WT mice due to the increased adiposity. Decreased glucose tolerance and insulin sensitivity were also observed in the HFD fed ASKO mice. Notably, the down-regulation of lipolysis-related genes and the decreased response to CL-316,243 stimulation in the HFD-fed ASKO mice suggested that these animals exhibited impaired lipolysis. In addition, the HFD-fed ASKO mice displayed impaired energy expenditure, indicating that the miR-200b/a/429 cluster is essential for developing adaptive responses to stressors such as HFD. For the first time, our studies demonstrated the essential role of miR-200b/a/429 in adipocytes in the regulation of HFD-induced whole-body metabolic changes. PMID- 27655720 TI - Sodium fluoride induces apoptosis in cultured splenic lymphocytes from mice. AB - Though fluorine has been shown to induce apoptosis in immune organs in vivo, there has no report on fluoride-induced apoptosis in the cultured lymphocytes. Therefore, this study was conducted with objective of investigating apoptosis induced by sodium fluoride (NaF) and the mechanism behind that in the cultured splenic lymphocytes by flow cytometry, western blot and Hoechst 33258 staining. The splenic lymphocytes were isolated from 3 weeks old male ICR mice and exposed to NaF (0, 100, 200, and 400 MUmol/L) in vitro for 24 and 48 h. When compared to control group, flow cytometry assay and Hoechst 33258 staining showed that NaF induced lymphocytes apoptosis, which was promoted by decrease of mitochondria transmembrane potential, up-regulation of Bax, Bak, Fas, FasL, caspase 9, caspase 8, caspase 7, caspase 6 and caspase 3 protein expression (P < 0.05 or P <0.01), and down-regulation of Bcl-2 and Bcl-xL protein expression (P <0.05 or P <0.01). The above-mentioned data suggested that NaF-induced apoptosis in splenic lymphocytes could be mediated by mitochondrial and death receptor pathways. PMID- 27655721 TI - Functional genetic variant in the Kozak sequence of WW domain-containing oxidoreductase (WWOX) gene is associated with oral cancer risk. AB - In Taiwan, oral cancer is the fourth leading cancer in males and is associated with exposure to environmental carcinogens. WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the development of various cancers. We hypothesized that genetic variants of WWOX influence the susceptibility to oral cancer. Five polymorphisms of WWOX gene from 761 male patients with oral cancer and 1199 male cancer-free individuals were genotyped. We observed that individuals carrying the polymorphic allele of WWOX rs11545028 are more susceptible to oral cancer. Furthermore, patients with advanced-stage oral cancer were associated with a higher frequency of WWOX rs11545028 polymorphisms with the variant genotype TT than did patients with the wild-type gene. An additional integrated in silico analysis confirmed that rs11545028 affects WWOX expression, which significantly correlates with tumor expression and subsequently with tumor development and aggressiveness. In conclusion, genetic variants of WWOX contribute to the occurrence of oral cancer, and the findings regarding these biomarkers provided a prediction model for risk assessment. PMID- 27655722 TI - Impact of label-free technologies in head and neck cancer circulating tumour cells. AB - BACKGROUND: The ability to identify high risk head and neck cancer (HNC) patients with disseminated disease prior to presenting with clinically detectable metastases holds remarkable potential. A fraction of circulating tumour cells (CTCs) are invasive cancer cells which mediate metastasis by intravasation, survival and extravasation from the blood stream to metastatic sites. CTCs have been cleared by the FDA for use as surrogate markers of overall survival and progression free survival for breast, prostate and colorectal cancers using the CellSearch(r) system. However, the clinical significance of CTCs in head and neck cancer patients has yet to be determined. There has been a significant shift in CTC enrichment platforms, away from exclusively single marker selection, to epitope-independent systems. METHODS: The aim of this study was to screen advanced stage HNC patients by the CellSearch(r) platform and utilise two other epitope-independent approaches, ScreenCell(r) (microfiltration device) and RosetteSepTM (negative enrichment), to determine how a shift to such methodologies would enable CTC enrichment and detection. RESULTS: In advanced stage HNC patients, single CTCs were detected in 8/43 (18.6%) on CellSearch(r), 13/28 (46.4%) on ScreenCell(r) and 16/25 (64.0%) by RosetteSepTM (the latter could also detect CTC clusters). Notably, in patients with suspicious lung nodules, too small to biopsy, CTCs were found upon presentation. Moreover, CTCs were readily detected in advanced stage HNC patients. CONCLUSION: The epitope independent platforms detected higher CTC numbers and clusters. Further studies are needed to ascertain whether CTCs can be used as independent prognostic markers for HNCs. PMID- 27655723 TI - Nitric oxide, PKC-epsilon, and connexin43 are crucial for ischemic preconditioning-induced chemical gap junction uncoupling. AB - Ischemic preconditioning (IPC) maintains connexin43 (Cx43) phosphorylation and reduces chemical gap junction (GJ) coupling in cardiomyocytes to protect against ischemic damage. However, the signal transduction pathways underlying these effects are not fully understood. Here, we investigated whether nitric oxide (NO) and protein kinase C-epsilon (PKC-epsilon) contribute to IPC-induced cardioprotection by maintaining Cx43 phosphorylation and inhibiting chemical GJ coupling. IPC reduced ischemia-induced myocardial infarction and increased cardiomyocyte survival; phosphorylated Cx43, eNOS, and PKC-epsilon levels; and chemical GJ uncoupling. Administration of the NO donor SNAP mimicked the effects of IPC both in vivo and in vitro, maintaining Cx43 phosphorylation, promoting chemical GJ uncoupling, and reducing myocardial infarction. Preincubation with the NO synthase inhibitor L-NAME or PKC-epsilon translocation inhibitory peptide (PKC-epsilon-TIP) abolished these effects of IPC. Additionally, by inducing NO production, IPC induced translocation of PKC-epsilon, but not PKC-delta, from the cytosolic to the membrane fraction in primary cardiac myocytes. IPC-induced cardioprotection thus involves increased NO production, PKC-epsilon translocation, Cx43 phosphorylation, and chemical GJ uncoupling. PMID- 27655724 TI - Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors. AB - PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management. PMID- 27655725 TI - Management of advanced gastric cancer: An overview of major findings from meta analysis. AB - This study aims to provide an overview of different treatment for advanced gastric cancer. In the present study, we systematically reviewed the major findings from relevant meta-analyses. A total of 54 relevant papers were searched via the PubMed, Web of Science, and Google scholar databases. They were classified according to the mainstay treatment modalities such as surgery, chemotherapy and others. Primary outcomes including overall survival, response rate, disease-free survival, recurrence-free survival, progression-free survival, time-to-progression, time-to failure, recurrence and safety were summarized. The recommendations and uncertainties regarding the treatment of advanced gastric cancer were also proposed. It was suggested that laparoscopic gastrectomy was a safe and technical alternative to open gastrectomy. Besides, neoadjuvant chemotherapy and adjuvant chemotherapy were thought to benefit the survival over surgery alone. And it was demonstrated in the study that targeted therapy like anti-angiogenic and anti-HER2 agents but anti-EGFR agent might have a significant survival benefit. PMID- 27655726 TI - Gamma-interferon-inducible, lysosome/endosome-localized thiolreductase, GILT, has anti-retroviral activity and its expression is counteracted by HIV-1. AB - The mechanism by which type II interferon (IFN) inhibits virus replications remains to be identified. Murine leukemia virus (MLV) replication was significantly restricted by gamma-IFN, but not human immunodeficiency virus type 1 (HIV-1) replication. Because MLV enters host cells via endosomes, we speculated that certain cellular factors among gamma-IFN-induced, endosome-localized proteins inhibit MLV replication. We found that gamma-IFN-inducible lysosomal thiolreductase (GILT) significantly restricts HIV-1 replication as well as MLV replication by its thiolreductase activity. GILT silencing enhanced replication defective HIV-1 vector infection and virion production in gamma-IFN-treated cells, although gamma-IFN did not inhibit HIV-1 replication. This result showed that GILT is required for the anti-viral activity of gamma-IFN. Interestingly, GILT protein level was increased by gamma-IFN in uninfected cells and env-deleted HIV-1-infected cells, but not in full-length HIV-1-infected cells. gamma-IFN induced transcription from the gamma-IFN-activation sequence was attenuated by the HIV-1 Env protein. These results suggested that the gamma-IFN cannot restrict HIV-1 replication due to the inhibition of gamma-IFN signaling by HIV-1 Env. Finally, we found that 4,4'-dithiodipyridine (4-PDS), which inhibits S-S bond formation at acidic pH, significantly suppresses HIV-1 vector infection and virion production, like GILT. In conclusion, this study showed that GILT functions as a host restriction factor against the retroviruses, and a GILT mimic, 4-PDS, is the leading compound for the development of novel concept of anti-viral agents. PMID- 27655729 TI - Suicidal Risks in Report of Reports of Long-Term Treatment Trials for Major Depressive Disorder. PMID- 27655727 TI - Colony-forming unit cell (CFU-C) assays at diagnosis: CFU-G/M cluster predicts overall survival in myelodysplastic syndrome patients independently of IPSS-R. AB - BACKGROUND: In vitro colony-forming unit cell (CFU-C) assays are usually-used to detect the quantitative and qualitative features of haematopoietic stem cells (HSCs). We studies CFU-C assays in bone marrow samples from 365 consecutive subjects with newly-diagnosed myelodysplastic syndrome (MDS). Data were interrogated for associations with prognosis. METHODS: CFU-C assays were performed according to the protocol of MethoCultTM H4435 Enriched. 365 consecutive newly-diagnosed, untreated subjects with MDS diagnosed from July, 2007 to April, 2014 were studied. All subjects were reclassified according to the 2008 WHO criteria. Subjects were observed for survival until July 31, 2015. Follow-up data were available for 289 (80%) subjects. Median follow-up of survivors was 22 months (range, 1-85) months. Erythroid and myeloid colonies were isolated from each subject with one cytogenetic abnormality such as del(5/5q), +8, del(7/7q) or del(20q). Cytogenetic abnormalities of each colony were analyzed by fluorescence in situ hybridization (FISH). SPSS 17.0 software was used to make statistical analysis. RESULTS: The numbers of burst-forming units-erythroid (BFU E), colony forming unit-erythroid (CFU-E) and colony forming unit granulocytes/macrophages (CFU-G/M) were significantly lower than normals. A high ratio of cluster- to CFU-G/M was associated with poor-risk cytogenetics. In multivariable analyses a cluster- to CFU-G/M ratio >0.6 was an independent risk factor for OS after adjusting for IPSS-R (HR 3.339, [95%CI 1.434-7.778]; P = 0.005) in very high-risk cohort. CONCLUSION: These data suggest abnormalities of proliferation and differentiation of erythroid and myeloid precursor cells in vitro parallel the ineffective hematopoiesis typical of MDS and may be useful in predicting outcomes of persons with higher-risk MDS. PMID- 27655730 TI - The outer membrane phospholipase A is essential for membrane integrity and type III secretion in Shigella flexneri. AB - Outer membrane phospholipase A (OMPLA) is an enzyme located in the outer membrane of Gram-negative bacteria. OMPLA exhibits broad substrate specificity, and some of its substrates are located in the cellular envelope. Generally, the enzymatic activity can only be induced by perturbation of the cell envelope integrity through diverse methods. Although OMPLA has been thoroughly studied as a membrane protein in Escherichia coli and is constitutively expressed in many other bacterial pathogens, little is known regarding the functions of OMPLA during the process of bacterial infection. In this study, the proteomic and transcriptomic data indicated that OMPLA in Shigella flexneri, termed PldA, both stabilizes the bacterial membrane and is involved in bacterial infection under ordinary culture conditions. A series of physiological assays substantiated the disorganization of the bacterial outer membrane and the periplasmic space in the DeltapldA mutant strain. Furthermore, the DeltapldA mutant strain showed decreased levels of type III secretion system expression, contributing to the reduced internalization efficiency in host cells. The results of this study support that PldA, which is widespread across Gram-negative bacteria, is an important factor for the bacterial life cycle, particularly in human pathogens. PMID- 27655731 TI - Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones. AB - As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from Streptococcus pneumoniae, we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from S. pneumoniae and an 18-base-pair DNA binding site-the E site-found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo et al. 2005 J. Biol. Chem. 280, 14 252-14 263, doi:10.1074/jbc.M500156200). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of beta-lactams and a range of ribosome bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site. PMID- 27655732 TI - A role for the p53 tumour suppressor in regulating the balance between homologous recombination and non-homologous end joining. AB - Loss of p53, a transcription factor activated by cellular stress, is a frequent event in cancer. The role of p53 in tumour suppression is largely attributed to cell fate decisions. Here, we provide evidence supporting a novel role for p53 in the regulation of DNA double-strand break (DSB) repair pathway choice. 53BP1, another tumour suppressor, was initially identified as p53 Binding Protein 1, and has been shown to inhibit DNA end resection, thereby stimulating non-homologous end joining (NHEJ). Yet another tumour suppressor, BRCA1, reciprocally promotes end resection and homologous recombination (HR). Here, we show that in both human and mouse cells, the absence of p53 results in impaired 53BP1 focal recruitment to sites of DNA damage induced by ionizing radiation. This effect is largely independent of cell cycle phase and the extent of DNA damage. In p53-deficient cells, diminished localization of 53BP1 is accompanied by a reciprocal increase in BRCA1 recruitment to DSBs. Consistent with these findings, we demonstrate that DSB repair via NHEJ is abrogated, while repair via homology-directed repair (HDR) is stimulated. Overall, we propose that in addition to its role as an 'effector' protein in the DNA damage response, p53 plays a role in the regulation of DSB repair pathway choice. PMID- 27655733 TI - Differential sub-nuclear distribution of hypoxia-inducible factors (HIF)-1 and -2 alpha impacts on their stability and mobility. AB - Cellular adaptation to hypoxia occurs via a complex programme of gene expression mediated by the hypoxia-inducible factor (HIF). The oxygen labile alpha subunits, HIF-1alpha/-2alpha, form a heterodimeric transcription factor with HIF-1beta and modulate gene expression. HIF-1alpha and HIF-2alpha possess similar domain structure and bind to the same consensus sequence. However, they have different oxygen-dependent stability and activate distinct genes. To better understand these differences, we used fluorescent microscopy to determine precise localization and dynamics. We observed a homogeneous distribution of HIF-1alpha in the nucleus, while HIF-2alpha localized into speckles. We demonstrated that the number, size and mobility of HIF-2alpha speckles were independent of cellular oxygenation and that HIF-2alpha molecules were capable of exchanging between the speckles and nucleoplasm in an oxygen-independent manner. The concentration of HIF-2alpha into speckles may explain its increased stability compared with HIF 1alpha and its slower mobility may offer a mechanism for gene specificity. PMID- 27655735 TI - Diabetes, the brain, and cognition: More clues to the puzzle. PMID- 27655734 TI - Cognitive decline following incident and preexisting diabetes mellitus in a population sample. AB - OBJECTIVE: To examine if incident and preexisting diabetes mellitus (DM) were associated with cognitive decline among African Americans (AAs) and European Americans (EAs). METHODS: Based on a prospective study of 7,740 older adults (mean age 72.3 years, 64% AA, 63% female), DM was ascertained by hypoglycemic medication use and Medicare claims during physician or hospital visits, and cognition by performance on a brief battery for executive functioning, episodic memory, and Mini-Mental State Examination (MMSE). Decline in composite and individual tests among those with incident DM, with preexisting DM, and without DM was studied using a linear mixed effects model with and without change point. RESULTS: At baseline, 737 (15%) AAs and 269 (10%) EAs had preexisting DM. Another 721 (17%) AAs and 289 (12%) EAs had incident DM in old age. Following incident DM, cognitive decline increased by 36% among AAs and by 40% among EAs compared to those without DM. No significant difference was observed between AAs and EAs (p = 0.64). However, cognitive decline increased by 17% among AAs with preexisting DM compared to those without DM, but no increased decline was observed among EAs with preexisting DM. In secondary analyses, faster decline in executive functioning and episodic memory was observed following incident DM. CONCLUSIONS: In old age, faster cognitive decline was present among AAs and EAs following incident DM, compared to cognitive decline prior to DM, and among those without DM. This underscores the need for stronger prevention and control of DM in old age. PMID- 27655737 TI - Involvement of the nucleus accumbens and dopamine system in chronic pain. PMID- 27655736 TI - Social cognition in multiple sclerosis: A systematic review and meta-analysis. AB - OBJECTIVE: To quantify the magnitude of deficits in theory of mind (ToM) and facial emotion recognition among patients with multiple sclerosis (MS) relative to healthy controls. METHODS: An electronic database search of Ovid MEDLINE, PsycINFO, and Embase was conducted from inception to April 1, 2016. Eligible studies were original research articles published in peer-reviewed journals that examined ToM or facial emotion recognition among patients with a diagnosis of MS and a healthy control comparison group. Data were independently extracted by 2 authors. Effect sizes were calculated using Hedges g. RESULTS: Twenty-one eligible studies were identified assessing ToM (12 studies) and/or facial emotion recognition (13 studies) among 722 patients with MS and 635 controls. Deficits in both ToM (g = -0.71, 95% confidence interval [CI] -0.88 to -0.55, p < 0.001) and facial emotion recognition (g = -0.64, 95% CI -0.81 to -0.47, p < 0.001) were identified among patients with MS relative to healthy controls. The largest deficits were observed for visual ToM tasks and for the recognition of negative facial emotional expressions. Older age predicted larger emotion recognition deficits. Other cognitive domains were inconsistently associated with social cognitive performance. CONCLUSIONS: Social cognitive deficits are an overlooked but potentially important aspect of cognitive impairment in MS with potential prognostic significance for social functioning and quality of life. Further research is required to clarify the longitudinal course of social cognitive dysfunction, its association with MS disease characteristics and neurocognitive impairment, and the MS-specific neurologic damage underlying these deficits. PMID- 27655739 TI - Applying Critical Discourse Analysis in Health Policy Research: Case Studies in Regional, Organizational, and Global Health. AB - Critical discourse analysis (CDA) is a promising methodology for policy research in nursing. As a critical theoretical methodology, researchers use CDA to analyze social practices and language use in policies to examine whether such policies may promote or impede social transformation. Despite the widespread use of CDA in other disciplines such as education and sociology, nursing policy research employing CDA methodology is sparse. To advance CDA use in nursing science, it is important to outline the overall research strategies and describe the steps of CDA in policy research. This article describes, using exemplar case studies, how nursing and health policy researchers can employ CDA as a methodology. Three case studies are provided to discuss the application of CDA research methodologies in nursing policy research: (a) implementation of preconception care policies in the Zhejiang province of China, (b) formation and enactment of statewide asthma policy in Washington state of the United States, and (c) organizational implementation of employee antibullying policies in hospital systems in the Pacific Northwest of the United States. Each exemplar details how CDA guided the examination of policy within specific contexts and social practices. The variations of the CDA approaches in the three exemplars demonstrated the flexibilities and potentials for conducting policy research grounded in CDA. CDA provides novel insights for nurse researchers examining health policy formation, enactment, and implementation. PMID- 27655738 TI - Long-term improvement in obsessions and compulsions with subthalamic stimulation. PMID- 27655740 TI - Mitral valve laceration: an unusual complication during transcatheter aortic valve replacement. PMID- 27655745 TI - Video-assisted thoracoscopic surgery versus open lobectomy for lung cancer: time for a randomized trial. PMID- 27655741 TI - Closure of a high ventricular septal defect after transcatheter aortic valve implantation with an atrial septal occluder-hybrid treatment for a rare complication. AB - A patient with porcelain aorta underwent transcatheter aortic valve implantation with a self-expandable prosthesis for severe aortic stenosis. After postdilatation trace paravalvular regurgitation was accepted. 10 weeks later the patient returned with complete heart block and underwent pacemaker implantation. A new heart murmur prompted further investigation. A ventricular septal defect from the left ventricular outflow tract into the right ventricle was detected. It was successfully closed under direct surgical visualization and total cardiopulmonary bypass in an aortic no touch approach. Closure was accomplished with a percutaneous Amplatzer-PFO-occluder. Functional result was excellent. PMID- 27655749 TI - An Intention-Based Account of Perspective-Taking: Why Perspective-Taking Can Both Decrease and Increase Moral Condemnation. AB - Perspective-taking often increases generosity in behavior and attributions. We present an intentions-based account to explain how perspective-taking can both decrease and increase moral condemnation. Consistent with past research, we predicted perspective-taking would reduce condemnation when the perspective-taker initially attributed benevolent intent to a transgressor. However, we predicted perspective-taking would increase condemnation when malevolent intentions were initially attributed to the wrongdoer. We propose that perspective-taking amplifies the intentions initially attributed to a transgressor. Three studies measured and manipulated intention attributions and found that perspective-taking increased condemnation when malevolent intentions were initially attributed to a transgressor. Perspective-taking also increased costly punishment of a transgressor, an effect mediated by malevolent intentions. In contrast, empathy did not increase punitive responses, supporting its conceptual distinction from perspective-taking. Whether perspective-taking leads to forgiveness or condemnation depends on the intentions the perspective-taker initially attributes to a transgressor. PMID- 27655748 TI - Helium-related hepatic necrosis due to intra-aortic balloon pump leakage. PMID- 27655750 TI - Testing the Link Between Empathy and Lay Theories of Happiness. AB - Happiness is a topic that ignites both considerable interest and considerable disagreement. Thus far, however, there has been little attempt to characterize people's lay theories about happiness or explore their consequences. We examined whether individual differences in lay theories of happiness would predict empathy. In Studies 1a and 1b, we validated the Lay Theories of Happiness Scale (LTHS), which includes three dimensions: flexibility, controllability, and locus. In Study 2, higher dispositional empathy was predicted by the belief that happiness is flexible, controllable, and internal. In Studies 3 and 4, higher empathy toward a specific target was predicted by the belief that happiness is flexible, uncontrollable, and external. In conjunction, Studies 2, 3, and 4 provide evidence that trait and state empathy are separable and can have opposing relationships with people's lay theories. Overall, these findings highlight generalized beliefs that may guide empathic reactions to the unhappiness of others. PMID- 27655751 TI - Personality Traits, Ego Development, and the Redemptive Self. AB - Life narratives are the internalized stories that people construct to provide meaning, purpose, and coherence in their lives. Prior research suggests that psychologically healthy and socially engaged adults generally narrate their lives in a prototypical fashion labeled the redemptive self, consisting of five themes: (a) a sense of childhood advantage, (b) empathy for others' sufferings, (c) moral steadfastness, (d) turning of negative events into positive outcomes (redemption sequences), and (e) prosocial goals. The current study examines trait correlates of the redemptive self in 157 late-midlife adults. Summing thematic scores across 12 life story interview scenes, the redemptive self was positively associated with four of the Big Five traits: extraversion, conscientiousness, agreeableness, and emotional stability, but unrelated to cognitive features of personality, as assessed on openness and ego development. The findings suggest those with positive socio-emotional personality traits, but not necessarily a proclivity for sophisticated thoughts, tend to have redemptive life stories. PMID- 27655752 TI - Straying From the Righteous Path and From Ourselves: The Interplay Between Perceptions of Morality and Self-Knowledge. AB - The present research addresses the relationship between morally valenced behavior and perceptions of self-knowledge, an outcome that has received little attention in moral psychology. We propose that morally valenced behavior is related to subjective perceptions of self-knowledge, such that people experience lower levels of self-knowledge when they are reminded of their immoral behaviors. We tested this proposition in four studies ( N = 1,177). Study 1 used daily-diary methods and indicates that daily perceptions of self-knowledge covary with daily levels of morally valenced behavior. The final three studies made use of experimental methods and demonstrate that thinking about immoral behaviors attenuates current perceptions of self-knowledge. The predicted relationships and effects generally persist when controlling for self-esteem. Based on our findings, we argue that perceived self-knowledge may play a functional role in moral self-concept maintenance and moral regulatory processes. PMID- 27655753 TI - Beyond Affective Influences on Deontological Moral Judgment: The Role of Motivations for Prevention in the Moral Condemnation of Harm. AB - Past research suggests that deontological judgments, which condemn deliberate harm no matter what the beneficial consequences, typically arise from emotional and intuitive reactions to the harm, whereas utilitarian judgments, which acknowledge the potential benefits of deliberate harm, typically arise from rational deliberation about whether these benefits outweigh the costs. The present research explores whether specific motivational orientations might, at times, increase the likelihood of deontological judgments without increasing emotional reactions. A meta-analysis of 10 newly conducted studies indicated that, compared with when focused on advancement ( promotion), when people were focused on security ( prevention) they made stronger deontological judgments in hypothetical moral dilemmas. Moreover, this effect could not be explained by participants' differing emotional reactions to the dilemmas when prevention focused, but instead mirrored reports of their explicit reasoning. Implications for expanding current models of deontological and utilitarian moral judgment are discussed. PMID- 27655754 TI - Were they in the loop during automated driving? Links between visual attention and crash potential. AB - BACKGROUND: A proposed advantage of vehicle automation is that it relieves drivers from the moment-to-moment demands of driving, to engage in other, non driving related, tasks. However, it is important to gain an understanding of drivers' capacity to resume manual control, should such a need arise. As automation removes vehicle control-based measures as a performance indicator, other metrics must be explored. METHODS: This driving simulator study, conducted under the European Commission (EC) funded AdaptIVe project, assessed drivers' gaze fixations during partially-automated (SAE Level 2) driving, on approach to critical and non-critical events. Using a between-participant design, 75 drivers experienced automation with one of five out-of-the-loop (OOTL) manipulations, which used different levels of screen visibility and secondary tasks to induce varying levels of engagement with the driving task: 1) no manipulation, 2) manipulation by light fog, 3) manipulation by heavy fog, 4) manipulation by heavy fog plus a visual task, 5) no manipulation plus an n-back task. RESULTS: The OOTL manipulations influenced drivers' first point of gaze fixation after they were asked to attend to an evolving event. Differences resolved within one second and visual attention allocation adapted with repeated events, yet crash outcome was not different between OOTL manipulation groups. Drivers who crashed in the first critical event showed an erratic pattern of eye fixations towards the road centre on approach to the event, while those who did not demonstrated a more stable pattern. CONCLUSIONS: Automated driving systems should be able to direct drivers' attention to hazards no less than 6 seconds in advance of an adverse outcome. PMID- 27655755 TI - Daily Cholecalciferol Supplementation during Pregnancy Alters Markers of Regulatory Immunity, Inflammation, and Clinical Outcomes in a Randomized Controlled Trial. AB - BACKGROUND: Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions in mothers and infants. Vitamin D supplementation in pregnancy may support the maintenance of pregnancy by its effects on innate and adaptive immunity. OBJECTIVE: We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status and markers of immune function associated with adverse pregnancy outcomes. METHODS: We conducted a randomized, controlled, double-blind intervention of 2 doses of cholecalciferol (400 and 2000 IU/d) from <20 wk to delivery in 57 pregnant women. Vitamin D status, regulatory and inflammatory T cells, markers of innate immunity and systemic inflammation, and clinical outcomes including maternal blood pressure and birth weight were assessed at 26 and 36 wk of pregnancy. RESULTS: Supplementation with 2000 IU/d vitamin D had a greater effect on the change in vitamin D status over pregnancy (P < 0.0001) and the final value at 36 wk (P < 0.0001) than 400 IU/d, increasing serum 25-hydroxyvitamin D from 81.1 nmol/L at baseline to 116 nmol/L at 36 wk and from 69.6 nmol/L at baseline to 85.6 nmol/L at 36 wk, respectively. The 2000-IU/d group had 36% more interleukin-10+ regulatory CD4+ T cells at 36 wk than did the 400-IU/d group (P < 0.007). The daily intake of 2000 compared with 400 IU/d tended to dampen the pregnancy related increase in diastolic blood pressure by 1.3-fold (P = 0.06) and increase birth weight by 8.6% (P = 0.06), but these differences were not statistically significant. CONCLUSIONS: Supplementation with 2000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory T cell immunity that may prevent adverse outcomes caused by excess inflammation. This trial was registered at clinicaltrials.gov as NCT01417351. PMID- 27655756 TI - Egg Consumption Increases Vitamin E Absorption from Co-Consumed Raw Mixed Vegetables in Healthy Young Men. AB - BACKGROUND: Most people living in the United States underconsume vitamin E, and dietary approaches to increase the absorption of vitamin E may help individuals to meet their body's needs. OBJECTIVE: We assessed the effect of adding cooked whole egg to a raw mixed-vegetable salad on alpha-tocopherol and gamma-tocopherol absorption. METHODS: With the use of a randomized-crossover design, 16 healthy young men [mean +/- SD age: 24 +/- 4 y; mean +/- SD body mass index (in kg/m2): 24 +/- 2] consumed the same salad (all served with 3 g canola oil) with no egg [control (CON)], with 75 g cooked egg [low egg (LE)], or with 150 g cooked egg [high egg (HE)]; a 1-wk dietary washout period was included between trials. For the first 7 d of each trial, participants consumed a low-vitamin E diet to reduce plasma vitamin E concentrations. Blood was collected hourly for 10 h and the triacylglycerol-rich lipoprotein fractions (TRLs) were isolated. alpha-Tocopherol and gamma-tocopherol concentrations in TRLs were analyzed and composite areas under the curve (AUCs) were calculated. RESULTS: The alpha-tocopherol 0- to 10-h AUCs (AUCs0-10 h) in TRLs was higher (P < 0.05) for the HE trial (least-squares mean +/- SE: 981 +/- 162 nmol/L ? 10 h) than for the LE (311 +/- 162 nmol/L ? 10 h) and CON (117 +/- 162 nmol/L ?10 h) trials, which did not differ from one another. The gamma-tocopherol AUCs0-10 h in TRLs was also higher (P < 0.05) for the HE trial (402 +/- 54 nmol/L ? 10 h) than for the CON trial (72 +/- 54 nmol/L ? 10 h). CONCLUSION: The consumption of cooked whole eggs is an effective way to increase the absorption of alpha-tocopherol and gamma-tocopherol from a co consumed meal that naturally contains vitamin E, such as a raw mixed-vegetable salad, in healthy young men. This trial was registered at clinicaltrials.gov as NCT01951313. PMID- 27655758 TI - Hepcidin Attenuates Zinc Efflux in Caco-2 Cells. AB - BACKGROUND: Hepcidin mediates the hypoferremia of inflammation by inhibiting iron transfer into circulation; however, a regulator for the hypozincemia observed in individuals with acute and chronic inflammatory and infectious diseases is not known. OBJECTIVE: The objective of this study was to determine the effects of hepcidin on zinc transport in intestinal epithelial cells. METHODS: Differentiated human intestinal Caco-2 cells were untreated or treated with 1 MUM hepcidin for 3-24 h. Zinc transport was assessed in cells seeded on Transwell inserts. Media from the apical and basolateral chambers were collected, and zinc concentrations were determined using 67Zn. Labile zinc pools were imaged and quantified in cells loaded with FluoZin-3-AM and expression of metallothionein and the zinc transporters zrt-/irt-like protein (ZIP)4 (SLC39A4), ZIP5 (SLC39A5), ZIP14 (SLC39A14), and zinc transporter 1 (ZnT1) (SLC30A1) was determined. Cells were transfected with SLC40A1- or SLC30A1-specific small interfering RNA to knock down ferroportin and ZnT1 protein, respectively. Cell surface proteins were isolated by cell surface biotinylation and lysosomal and proteasomal degradation was inhibited by treating cells with chloroquine or MG132, respectively. RESULTS: Hepcidin attenuated zinc transport, as cells treated with hepcidin exported 26% less 67Zn (P < 0.05) into the basolateral chamber and retained 27% more cellular 67Zn (P < 0.05) than did control cells. Labile zinc decreased, and the mRNA abundance of metallothionein increased by ~50% in hepcidin-treated cells compared with control cells (P < 0.05). Hepcidin reduced ZnT1 protein by 75% (P < 0.05) compared with control cells. Hepcidin-mediated reductions in zinc export remained in ferroportin knockdown cells compared with untreated controls (P < 0.05), whereas knockdown of ZnT1 inhibited this effect (P >= 0.05). Hepcidin significantly reduced biotinylated cell surface ZnT1 compared with control cells (P < 0.05); chloroquine inhibited hepcidin-mediated degradation of ZnT1 (P >= 0.05), whereas MG132 had no effect (P < 0.05). CONCLUSIONS: Hepcidin reduces intestinal zinc export by post-translationally downregulating ZnT1 through a lysosomal-mediated degradation pathway, indicating that hepcidin may contribute to the hypozincemia of inflammation and infection. PMID- 27655757 TI - Simulated Models Suggest That Price per Calorie Is the Dominant Price Metric That Low-Income Individuals Use for Food Decision Making. AB - BACKGROUND: The price of food has long been considered one of the major factors that affects food choices. However, the price metric (e.g., the price of food per calorie or the price of food per gram) that individuals predominantly use when making food choices is unclear. Understanding which price metric is used is especially important for studying individuals with severe budget constraints because food price then becomes even more important in food choice. OBJECTIVE: We assessed which price metric is used by low-income individuals in deciding what to eat. METHODS: With the use of data from NHANES and the USDA Food and Nutrient Database for Dietary Studies, we created an agent-based model that simulated an environment representing the US population, wherein individuals were modeled as agents with a specific weight, age, and income. In our model, agents made dietary food choices while meeting their budget limits with the use of 1 of 3 different metrics for decision making: energy cost (price per calorie), unit price (price per gram), and serving price (price per serving). The food consumption patterns generated by our model were compared to 3 independent data sets. RESULTS: The food choice behaviors observed in 2 of the data sets were found to be closest to the simulated dietary patterns generated by the price per calorie metric. The behaviors observed in the third data set were equidistant from the patterns generated by price per calorie and price per serving metrics, whereas results generated by the price per gram metric were further away. CONCLUSIONS: Our simulations suggest that dietary food choice based on price per calorie best matches actual consumption patterns and may therefore be the most salient price metric for low-income populations. PMID- 27655759 TI - Life-Course Body Mass Index Trajectories Are Predicted by Childhood Socioeconomic Status but Not Exposure to Improved Nutrition during the First 1000 Days after Conception in Guatemalan Adults. AB - BACKGROUND: Latin America has experienced increases in obesity. Little is known about the role of early life factors on body mass index (BMI) gain over the life course. OBJECTIVE: The objective of this research was to examine the role of early life factors [specifically, nutrition supplementation during the first 1000 d (from conception to 2 y of age) and childhood household socioeconomic status (SES)] on the pattern of BMI gain from birth or early childhood through midadulthood by using latent class growth analysis. METHODS: Study participants (711 women, 742 men) who were born in 4 villages in Guatemala (1962-1977) were followed prospectively since participating in a randomized nutrition supplementation trial as children. Sex-specific BMI latent class trajectories were derived from 22 possible measures of height and weight from 1969 to 2004. To characterize early life determinants of BMI latent class membership, we used logistic regression modeling and estimated the difference-in-difference (DD) effect of nutrition supplementation during the first 1000 d. RESULTS: We identified 2 BMI latent classes in women [low (57%) and high (43%)] and 3 classes in men [low (38%), medium (47%), and high (15%)]. Nutrition supplementation during the first 1000 d after conception was not associated with BMI latent class membership (DD test: P > 0.15 for men and women), whereas higher SES was associated with increased odds of high BMI latent class membership in both men (OR: 1.98; 95% CI: 1.09, 3.61) and women (OR: 1.62; 95% CI: 1.07, 2.45) for the highest relative to the lowest tertile. CONCLUSIONS: In a cohort of Guatemalan men and women, nutrition supplementation provided during the first 1000 d was not significantly associated with higher BMI trajectory. Higher childhood household SES was associated with increased odds of high BMI latent class membership relative to the poorest households. The pathways through which this operates still need to be explored. PMID- 27655760 TI - Flavanone Intake Is Inversely Associated with Risk of Incident Ischemic Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. AB - BACKGROUND: Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed. OBJECTIVES: We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence. METHODS: We evaluated 20,024 participants in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a biracial prospective study. Participants with stroke history or missing dietary data were excluded. Flavonoid intake was estimated by using a Block98 food frequency questionnaire and the USDA's Provisional Flavonoid Addendum and Proanthocyanidin Database. Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models, adjusting for confounders. RESULTS: Over 6.5 y, 524 acute ischemic strokes occurred. Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites. After multivariable adjustment, flavanone intake was inversely associated with incident ischemic stroke (HR: 0.72; 95% CI: 0.55, 0.95; P-trend = 0.03). Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke (HR: 0.69; 95% CI: 0.53, 0.91; P-trend = 0.02). Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke. There was no statistical interaction with sex, race, or region for any flavonoid measure. CONCLUSIONS: Greater consumption of flavanones, but not total or other flavonoid subclasses, was inversely associated with incident ischemic stroke. Associations did not differ by sex, race, or region for the association; however, regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence. Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence. PMID- 27655761 TI - Prior Consumption of a Fat Meal in Healthy Adults Modulates the Brain's Response to Fat. AB - BACKGROUND: The consumption of fat is regulated by reward and homeostatic pathways, but no studies to our knowledge have examined the role of high-fat meal (HFM) intake on subsequent brain activation to oral stimuli. OBJECTIVE: We evaluated how prior consumption of an HFM or water load (WL) modulates reward, homeostatic, and taste brain responses to the subsequent delivery of oral fat. METHODS: A randomized 2-way crossover design spaced 1 wk apart was used to compare the prior consumption of a 250-mL HFM (520 kcal) [rapeseed oil (440 kcal), emulsifier, sucrose, flavor cocktail] or noncaloric WL on brain activation to the delivery of repeated trials of a flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 men) aged 25 +/- 2 y and with a body mass index (in kg/m2) of 22.4 +/- 0.8. We tested differences in brain activation to the CS and FS and baseline cerebral blood flow (CBF) after the HFM and WL. We also tested correlations between an individual's plasma cholecystokinin (CCK) concentration after the HFM and blood oxygenation level dependent (BOLD) activation of brain regions. RESULTS: Compared to the WL, consuming the HFM led to decreased anterior insula taste activation in response to both the CS (36.3%; P < 0.05) and FS (26.5%; P < 0.05). The HFM caused reduced amygdala activation (25.1%; P < 0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula: 5.7%; P < 0.01), homeostatic (hypothalamus: 9.2%, P < 0.01; thalamus: 5.1%, P < 0.05), and reward areas (striatum: 9.2%; P < 0.01) after the HFM. An individual's plasma CCK concentration correlated negatively with brain activation in taste and oral somatosensory (rho = -0.39; P < 0.05) and reward areas (rho = -0.36; P < 0.05). CONCLUSIONS: Our results in healthy adults show that an HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain's response to high-fat counterparts and guide future interventions to reduce obesity. PMID- 27655762 TI - Predicting evolutionary rescue via evolving plasticity in stochastic environments. AB - Phenotypic plasticity and its evolution may help evolutionary rescue in a novel and stressful environment, especially if environmental novelty reveals cryptic genetic variation that enables the evolution of increased plasticity. However, the environmental stochasticity ubiquitous in natural systems may alter these predictions, because high plasticity may amplify phenotype-environment mismatches. Although previous studies have highlighted this potential detrimental effect of plasticity in stochastic environments, they have not investigated how it affects extinction risk in the context of evolutionary rescue and with evolving plasticity. We investigate this question here by integrating stochastic demography with quantitative genetic theory in a model with simultaneous change in the mean and predictability (temporal autocorrelation) of the environment. We develop an approximate prediction of long-term persistence under the new pattern of environmental fluctuations, and compare it with numerical simulations for short- and long-term extinction risk. We find that reduced predictability increases extinction risk and reduces persistence because it increases stochastic load during rescue. This understanding of how stochastic demography, phenotypic plasticity, and evolution interact when evolution acts on cryptic genetic variation revealed in a novel environment can inform expectations for invasions, extinctions, or the emergence of chemical resistance in pests. PMID- 27655763 TI - Synergistic impacts of habitat loss and fragmentation on model ecosystems. AB - Habitat loss and fragmentation are major threats to biodiversity, yet separating their effects is challenging. We use a multi-trophic, trait-based, and spatially explicit general ecosystem model to examine the independent and synergistic effects of these processes on ecosystem structure. We manipulated habitat by removing plant biomass in varying spatial extents, intensities, and configurations. We found that emergent synergistic interactions of loss and fragmentation are major determinants of ecosystem response, including population declines and trophic pyramid shifts. Furthermore, trait-mediated interactions, such as a disproportionate sensitivity of large-sized organisms to fragmentation, produce significant effects in shaping responses. We also show that top-down regulation mitigates the effects of land use on plant biomass loss, suggesting that models lacking these interactions-including most carbon stock models-may not adequately capture land-use change impacts. Our results have important implications for understanding ecosystem responses to environmental change, and assessing the impacts of habitat fragmentation. PMID- 27655764 TI - Prenatal stress effects in a wild, long-lived primate: predictive adaptive responses in an unpredictable environment. AB - Prenatal maternal stress affects offspring phenotype in numerous species including humans, but it is debated whether these effects are evolutionarily adaptive. Relating stress to adverse conditions, current explanations invoke either short-term developmental constraints on offspring phenotype resulting in decelerated growth to avoid starvation, or long-term predictive adaptive responses (PARs) resulting in accelerated growth and reproduction in response to reduced life expectancies. Two PAR subtypes were proposed, acting either on predicted internal somatic states or predicted external environmental conditions, but because both affect phenotypes similarly, they are largely indistinguishable. Only external (not internal) PARs rely on high environmental stability particularly in long-lived species. We report on a crucial test case in a wild long-lived mammal, the Assamese macaque (Macaca assamensis), which evolved and lives in an unpredictable environment where external PARs are probably not advantageous. We quantified food availability, growth, motor skills, maternal caretaking style and maternal physiological stress from faecal glucocorticoid measures. Prenatal maternal stress was negatively correlated to prenatal food availability and led to accelerated offspring growth accompanied by decelerated motor skill acquisition and reduced immune function. These results support the 'internal PAR' theory, which stresses the role of stable adverse internal somatic states rather than stable external environments. PMID- 27655765 TI - Climate change relaxes the time constraints for late-born offspring in a long distance migrant. AB - Animals in seasonal environments need to fit their annual-cycle stages, such as moult and migration, in a tight schedule. Climate change affects the phenology of organisms and causes advancements in timing of these annual-cycle stages but not necessarily at the same rates. For migratory birds, this can lead to more severe or more relaxed time constraints in the time from fledging to migration, depending on the relative shifts of the different stages. We tested how a shift in hatch date, which has advanced due to climate change, impacts the organization of the birds' whole annual cycle. We experimentally advanced and delayed the hatch date of pied flycatcher chicks in the field and then measured the timing of their annual-cycle stages in a controlled laboratory environment. Hatch date affected the timing of moult and pre-migratory fattening, but not migration. Early-born birds hence had a longer time to fatten up than late-born ones; the latter reduced their interval between onset of fattening and migration to be able to migrate at the same time as the early-born birds. This difference in time constraints for early- and late-born individuals may explain why early-born offspring have a higher probability to recruit as a breeding bird. Climate change associated advancements of avian egg-lay dates, which in turn advances hatch dates, can thus reduce the negative fitness consequences of reproducing late, thereby reducing the selection for early egg-laying migratory birds. PMID- 27655766 TI - Modelling the climatic niche of turtles: a deep-time perspective. AB - Ectotherms have close physiological ties with the thermal environment; consequently, the impact of future climate change on their biogeographic distributions is of major interest. Here, we use the modern and deep-time fossil record of testudines (turtles, tortoises, and terrapins) to provide the first test of climate on the niche limits of both extant and extinct (Late Cretaceous, Maastrichtian) taxa. Ecological niche models are used to assess niche overlap in model projections for key testudine ecotypes and families. An ordination framework is applied to quantify metrics of niche change (stability, expansion, and unfilling) between the Maastrichtian and present day. Results indicate that niche stability over evolutionary timescales varies between testudine clades. Groups that originated in the Early Cretaceous show climatic niche stability, whereas those diversifying towards the end of the Cretaceous display larger niche expansion towards the modern. Temperature is the dominant driver of modern and past distributions, whereas precipitation is important for freshwater turtle ranges. Our findings demonstrate that testudines were able to occupy warmer climates than present day in the geological record. However, the projected rate and magnitude of future environmental change, in concert with other conservation threats, presents challenges for acclimation or adaptation. PMID- 27655767 TI - The effect of aggregation on visibility in open water. AB - Aggregation is a common life-history trait in open-water taxa. Qualitative understanding of how aggregation by prey influences their encounter rates with predators is critical for understanding pelagic predator-prey interactions and trophic webs. We extend a recently developed theory on underwater visibility to predict the consequences of grouping in open-water species in terms of increased visual detection of groups by predators. Our model suggests that enhanced visibility will be relatively modest, with maximum detection distance typically only doubling for a 100-fold increase in the number of prey in a group. This result suggests that although larger groups are more easily detected, this cost to aggregation will in many cases be dominated by benefits, especially through risk dilution in situations where predators cannot consume all members of a discovered group. This, in turn, helps to explain the ubiquity of grouping across a great variety of open-water taxa. PMID- 27655769 TI - Probiotic treatment restores protection against lethal fungal infection lost during amphibian captivity. AB - Host-associated microbiomes perform many beneficial functions including resisting pathogens and training the immune system. Here, we show that amphibians developing in captivity lose substantial skin bacterial diversity, primarily due to reduced ongoing input from environmental sources. We combined studies of wild and captive amphibians with a database of over 1 000 strains that allows us to examine antifungal function of the skin microbiome. We tracked skin bacterial communities of 62 endangered boreal toads, Anaxyrus boreas, across 18 time points, four probiotic treatments, and two exposures to the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd) in captivity, and compared these to 33 samples collected from wild populations at the same life stage. As the amphibians in captivity lost the Bd-inhibitory bacteria through time, the proportion of individuals exposed to Bd that became infected rose from 33% to 100% in subsequent exposures. Inoculations of the Bd-inhibitory probiotic Janthinobacterium lividum resulted in a 40% increase in survival during the second Bd challenge, indicating that the effect of microbiome depletion was reversible by restoring Bd-inhibitory bacteria. Taken together, this study highlights the functional role of ongoing environmental inputs of skin-associated bacteria in mitigating a devastating amphibian pathogen, and that long-term captivity decreases this defensive function. PMID- 27655768 TI - Demographic mechanisms underpinning genetic assimilation of remnant groups of a large carnivore. AB - Current range expansions of large terrestrial carnivores are occurring following human-induced range contraction. Contractions are often incomplete, leaving small remnant groups in refugia throughout the former range. Little is known about the underlying ecological and evolutionary processes that influence how remnant groups are affected during range expansion. We used data from a spatially explicit, long-term genetic sampling effort of grizzly bears (Ursus arctos) in the Northern Continental Divide Ecosystem (NCDE), USA, to identify the demographic processes underlying spatial and temporal patterns of genetic diversity. We conducted parentage analysis to evaluate how reproductive success and dispersal contribute to spatio-temporal patterns of genetic diversity in remnant groups of grizzly bears existing in the southwestern (SW), southeastern (SE) and east-central (EC) regions of the NCDE. A few reproductively dominant individuals and local inbreeding caused low genetic diversity in peripheral regions that may have persisted for multiple generations before eroding rapidly (approx. one generation) during population expansion. Our results highlight that individual-level genetic and reproductive dynamics play critical roles during genetic assimilation, and show that spatial patterns of genetic diversity on the leading edge of an expansion may result from historical demographic patterns that are highly ephemeral. PMID- 27655771 TI - Circulating miRNAs in Murine Experimental Endometriosis. AB - Endometriosis is a chronic disease that commonly affects women of reproductive age; however, diagnosis is often delayed due to lack of appreciation of early signs and symptoms. Development of a noninvasive biomarker would significantly reduce delays in diagnosis and treatment. Circulating microRNAs (miRNAs) have been implicated as biomarkers for several diseases including endometriosis. Here, we use an miRNA array to investigate differential miRNA abundance in the serum of mice after induction of experimental endometriosis. let-7a-5p was decreased in the serum of mice with endometriosis. let-7b-5p, c-5p, and e-5p also showed a trend toward downregulation. Serum let-7 family miRNA shows similar dysregulation in endometriosis in both humans and mice. Diminished circulating let-7 implies a complex regulation that potentially involves multiple organs. Further investigation is necessary to determine the functional roles of let-7 miRNAs in this disease. PMID- 27655770 TI - Novel energy-saving strategies to multiple stressors in birds: the ultradian regulation of body temperature. AB - This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5 degrees C) or thermoneutrality (TN) (25 degrees C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting. PMID- 27655773 TI - Reducing time to surgery after anterior cruciate ligament injury. AB - INTRODUCTION: Recent work suggests that reconstruction of the ruptured anterior cruciate ligament within 12 months of injury results in better outcomes. We present a complete audit cycle examining the effect of establishment of an Acute Knee Clinic on time to surgery. METHODS: Records of 20 anterior cruciate ligament reconstructions undertaken by the senior author between June 2003 and May 2004 were examined to identify the time to surgery. The Acute Knee Clinic was established in December 2004. Prospectively collected data on patients attending the Acute Knee Clinic between May 2005 and July 2007 and patients undergoing anterior cruciate ligament reconstruction from September 2006 to 2007 were reviewed with respect to referral route, time from injury to specialist review and time to surgery. RESULTS: Mean time from injury to surgery of the initial cohort was 14 months (range 3-56). After establishment of the Acute Knee Clinic, 90% of referrals from Accident and Emergency (A&E) were seen by a specialist within four weeks. Between September 2006 and September 2007, 49 patients underwent anterior cruciate ligament reconstruction: 21 came via the Acute Knee Clinic, with a mean time from injury to surgery of 6 months; 28 patients from the elective clinic had a mean time to surgery of 25 months. 95% of Acute Knee Clinic patients and 53 % of elective clinic patients had surgery within 12 months of injury. DISCUSSION: The Acute Knee Clinic has been shown to reduce the time from injury to anterior cruciate ligament reconstruction. The Acute Knee Clinic only accounts for the referral of 40% of anterior cruciate ligament reconstructions in this series: Further education work is required with A&E staff and GPs regarding the referral of knee injuries. Access to the Acute Knee Clinic could be extended to GPs, although this could create service overload. PMID- 27655772 TI - Does the Presence of Blood in the Catheter or the Degree of Difficulty of Embryo Transfer Affect Live Birth? AB - The technique used for embryo transfer (ET) can affect implantation. Prior research that evaluated the effect of postprocedural blood of the transfer catheter tip have yielded mixed results, and it is unclear whether this is actually a marker of difficulty of the transfer. Our objective was to estimate the effect of blood at the time of ET and the difficulty of ET on live birth rates (LBR). This retrospective cohort study utilized generalized estimating equations (GEEs) with nesting for repeated cycles for all analyses. Univariate modeling was performed and a final multivariate (adjusted) GEE model accounted for all significant confounders. Embryo transfers were subjectively graded (easy, medium, or hard) by a physician at the time of transfer. The presence of blood at ET was associated with more difficult ETs, retained embryos, and presence of mucous in the catheter. In the univariate analysis, ET with blood was not associated with live birth, while the degree of difficulty for ET had a negative impact on LBR. In the final multivariate GEE model, which accounts for repeated cycles from a patient, the only factors associated with an increased LBR were the degree of difficulty of the ET, female age, and blastocyst transfer. After controlling for confounding variables, the presence of blood in the transfer catheter was not associated with the likelihood of pregnancy and thus was not an independent predictor of cycle outcome. This indicates that the difficulty of the transfer itself was a strong negative predictor of pregnancy. PMID- 27655774 TI - Sensitising effects of genetically modified enzymes used in flavour, fragrance, detergence and pharmaceutical production: cross-sectional study. AB - OBJECTIVES: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers. METHODS: Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys. RESULTS: Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from alpha-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6). CONCLUSIONS: Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays. PMID- 27655776 TI - Regulation of Lysophosphatidic Acid Metabolism and Signaling by Lipoproteins. PMID- 27655775 TI - Physical occupational exposures and health expectancies in a French occupational cohort. AB - OBJECTIVES: To examine the relationships of strenuous and hazardous working conditions and rotating shifts that involve night working with life expectancy in good perceived health and life expectancy without chronic disease. METHODS: The sample contained male gas and electricity workers from the French GAZEL cohort (n=13 393). Six measures of physical working conditions were examined: Self reports from 1989 and 1990 of ergonomic strain, physical danger, rotating shifts that involve night working and perceived physical strain; company records of workplace injuries and a job-exposure matrix of chemical exposures. Partial healthy life expectancies (age 50-75) relating to (1) self-rated health and (2) chronic health conditions, obtained from annual questionnaires (1989-2014) and company records, were estimated using multistate life tables. The analyses were adjusted for social class and occupational grade. RESULTS: Participants with physically strenuous jobs and who had experienced industrial injuries had shorter partial life expectancy. More physically demanding and dangerous work was associated with fewer years of life spent in good self-rated health and without chronic conditions, with the exception of shift work including nights, where the gradient was reversed. CONCLUSIONS: Strenuous and hazardous work may contribute to lost years of good health in later life, which has implications for individuals' quality of life as well as healthcare use and labour market participation. PMID- 27655777 TI - Metabolic Manipulation to Put the Brakes on Platelet Activation: A Potential Novel Pharmacologic Approach to Atherothrombosis. PMID- 27655778 TI - (MYO)SLIDing Our Way Into the Vascular Pool of Long Noncoding RNAs. PMID- 27655779 TI - NETs Activate Pulmonary Arterial Endothelial Cells. PMID- 27655781 TI - Subjective health literacy: Development of a brief instrument for school-aged children. AB - AIMS: The present paper focuses on the measurement of health literacy (HL), which is an important determinant of health and health behaviours. HL starts to develop in childhood and adolescence; hence, there is a need for instruments to monitor HL among younger age groups. These instruments are still rare. The aim of the project reported here was, therefore, to develop a brief, multidimensional, theory-based instrument to measure subjective HL among school-aged children. METHODS: The development of the instrument covered four phases: item generation based on a conceptual framework; a pilot study ( n = 405); test-retest ( n = 117); and construction of the instrument ( n = 3853). All the samples were taken from Finnish 7th and 9th graders. RESULTS: Initially, 65 items were generated, of which 32 items were selected for the pilot study. After item reduction, the instrument contained 16 items. The test-retest phase produced estimates of stability. In the final phase a 10-item instrument was constructed, referred to as Health Literacy for School-Aged Children (HLSAC). The instrument exhibited a high Cronbach alpha (0.93), and included two items from each of the five predetermined theoretical components (theoretical knowledge, practical knowledge, critical thinking, self-awareness, citizenship). CONCLUSIONS: The iterative and validity-driven development process made it possible to construct a brief multidimensional HLSAC instrument. Such instruments are suitable for large-scale studies, and for use with children and adolescents. Validation will require further testing for use in other countries. PMID- 27655780 TI - Vascular Smooth Muscle Cells. PMID- 27655782 TI - Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors. AB - AIMS: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). METHODS: Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. RESULTS: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). CONCLUSIONS: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people. PMID- 27655783 TI - Health-related quality of life of Finnish patients with diabetes. AB - AIMS: This study evaluated the influence of diabetes on the health-related quality of life (HRQoL) scores of adult patients with diabetes in northern Finland. METHODS: A total of 3771 patients of the population of 10,264 patients aged ?15 years with the right for reimbursement of the cost of diabetes medication attended fundus photography screening for retinopathy in 2012. The 15D HRQoL scores and data on age, sex, type and duration of diabetes were gathered concurrently. The results were compared with the 15D scores reported in Finnish population studies. RESULTS: The 15D score was obtained from 2461 patients aged 60+/-14 years; 20% had type 1 diabetes (T1D). The mean+/-SD 15D index was 0.930+/ 0.079 in patients with T1D and their mean+/-SD age was 46+/-15 years. The mean+/ SD 15D index of the patients with type 2 diabetes (T2D) was 0.890+/-0.100 and their mean+/-SD age was 63+/-11 years. The 15D index was no lower than in the Finnish general population in either patient group or in any age group. However, the 15D score was negatively influenced by an increasing duration of diabetes in both patients with T1D and patients with T2D. No sex difference was found. CONCLUSIONS: The mean HRQoL score of patients with diabetes in this study is comparable with that of the general population of equal age. Neither the type of diabetes nor sex independently affected the HRQoL score, but a longer duration of diabetes seemed to impair the HRQoL score. Current diabetes care appears to maintain a normal HRQoL score in this diabetic population in Finland. PMID- 27655785 TI - Functional Roles of Fructose: Crosstalk between O-Linked Glycosylation and Phosphorylation of Akt-TSC2-MTOR Cell Signaling Cascade in Ovine Trophectoderm Cells. AB - During pregnancy, the placentae of ungulate mammals (e.g., cows, sheep, and pigs) convert glucose into fructose which is the most abundant hexose sugar in fetal fluids and blood. However, the role of fructose, the most enigmatic component of carbohydrate metabolism in fetal-placental tissues, is largely ignored since it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. Here we provided evidence for biological functions of fructose that affect proliferative behavior of the conceptus trophectoderm/chorion via activation of the Akt-TSC2-MTOR signaling cascade. The phosphorylation for activation of this cascade is mediated by O-GlcNAcylation from UDP-N acetylglucosamine (UDP-GlcNAc), a primary product of the hexosamine biosynthesis pathway. These results reveal novel functional roles of fructose in promoting embryonic/fetal growth and development during pregnancy, and also provide new insight into understanding the relationship between excessive fructose intake and metabolic disorders. PMID- 27655787 TI - How to do better health reform: a snapshot of change and improvement initiatives in the health systems of 30 countries. AB - Health systems are continually being reformed. Why, and how? To answer these questions, we draw on a book we recently contributed, Healthcare Reform, Quality and Safety: Perspectives, Participants, Partnerships and Prospects in 30 Countries. We analyse the impact that these health-reform initiatives have had on the quality and safety of care in an international context-that is, in low-, middle- and high-income countries-Argentina, Australia, Brazil, Chile, China, Denmark, England, Ghana, Germany, the Gulf states, Hong Kong, India, Indonesia, Israel, Italy, Japan, Mexico, Myanmar, New Zealand, Norway, Oman, Papua New Guinea (PNG), South Africa, the USA, Scotland and Sweden. Popular reforms in less well-off countries include boosting equity, providing infrastructure, and reducing mortality and morbidity in maternal and child health. In countries with higher GDP per capita, the focus is on new IT systems or trialling innovative funding models. Wealthy or less wealthy, countries are embracing ways to enhance quality of care and keep patients safe, via mechanisms such as accreditation, clinical guidelines and hand hygiene campaigns. Two timely reminders are that, first, a population's health is not determined solely by the acute system, but is a product of inter-sectoral effort-that is, measures to alleviate poverty and provide good housing, education, nutrition, running water and sanitation across the population. Second, all reformers and advocates of better-quality of care should include well-designed evaluation in their initiatives. Too often, improvement is assumed, not measured. That is perhaps the key message. PMID- 27655786 TI - Mutations in the MOV10L1 ATP Hydrolysis Motif Cause piRNA Biogenesis Failure and Male Sterility in Mice. AB - Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs. piRNAs protect the genome integrity of the germline by silencing active transposable elements and are essential for germ cell development. Most piRNA pathway proteins are evolutionarily conserved. MOV10L1, a testis-specific RNA helicase, binds to piRNA precursors and is a master regulator of piRNA biogenesis in mouse. Here we report that mutation of the MOV10L1 ATP hydrolysis site leads to depletion of piRNAs on Piwi proteins, de-repression of transposable elements, and conglomeration of piRNA pathway proteins into polar granules. The Mov10l1 mutant mice exhibit meiotic arrest and male sterility. Our results show that mutation of the MOV10L1 ATP hydrolysis site perturbs piRNA biogenesis. PMID- 27655784 TI - Extracellular Vesicles in the Intrauterine Environment: Challenges and Potential Functions. AB - Extracellular vesicles (EVs), including exosomes (30-150 nm) and microvesicles (100-1500 nm), play important roles in mediating cell-cell communication. Such particles package distinct cargo elements, including lipids, proteins, mRNAs, microRNAs, and DNA, that vary depending on the cell of origin and its phenotype. This cargo can be horizontally transferred to target cells where its components can reprogram the recipient cell to modify its function. EVs have been identified within the uterine cavity of women, sheep, and mice, where they contribute to the microenvironment of sperm transport, and of blastocyst and endometrial preparation for implantation. It is likely that exosomes and microvesicles carry different cargo and coordinate different roles in this intrauterine environment. Understanding and defining these subtypes of EVs is important for future functional studies and clinical translation. Here we critically review the various purification and validation procedures for extracellular vesicle analysis and discuss what is known of endometrial-derived exosome cargo and of their hormonal regulation. The current knowledge of the functions of uterine exosomes, with respect to sperm transport and function, and of their actions on trophectodermal cells to promote implantation are summarized and evaluated in their physiological context. Given the potential importance of this form of cell cell interactions within the reproductive tract, the critical issues discussed will guide new insights in this rapidly expanding field. PMID- 27655788 TI - Cost-effectiveness of implementing the chronic care model for HIV care in Uganda. AB - Objective: The chronic care model (CCM) is an integrated, population-based approach for treating those with chronic diseases that involves patient self management, delivery system design and decision support for clinicians to ensure evidence-based care. We sought to determine effectiveness and cost-effectiveness of implementing the CCM for HIV care in Uganda. Design: This controlled, pre/post intervention study used difference-in-differences analysis to evaluate effectiveness of the CCM to improve patient adherence to antiretroviral therapy (ART) and CD4 counts. Setting: One district hospital and two smaller facilities each in one intervention and one control district in Uganda. Participants: About 46 randomly sampled patients receiving HIV services at three control sites and 56 patients from three intervention sites. Intervention: Two group training sessions and monthly coaching visits from improvement experts over 1 year, implementing the CCM. Main Outcome Measure(s): Patient adherence to ART prescriptions (pill counts) and CD4 counts were measured at baseline and en dline. Results: The odds of increased CD4 in the intervention group was 3.2 times higher than controls (P = 0.022). Clinician-reported ART adherence was 60% (P = 0.001) higher in the intervention group. The intervention cost $11 740 and served 7016 patients ($1.67 per patient). Incremental cost-effectiveness ratios of the intervention compared to business-as-usual was $6.90 per additional patient with improved CD4 and $3.40 per additional ART patient with stable or improved adherence. Conclusion: For modest expenditure, it is possible to improve indicators of HIV care quality using the CCM. We recommended implementing the CCM in Uganda; it may be applicable in similar settings in other countries. PMID- 27655789 TI - Intra-hospital correlations among 30-day mortality rates in 18 different clinical and surgical settings. AB - Objective: To examine whether a correlation exists in hospitals among 30-day mortality rates for different types of hospitalizations. Design: Cross-sectional study of hospital care based on publically available Italian data from the National Outcome Evaluation Program Edition 2015 of the Italian Agency for Regional Health Services. Setting and Participants: Patients hospitalized with a diagnosis of congestive heart failure, acute myocardial infarction, chronic renal failure, chronic obstructive pulmonary disease exacerbation, femoral neck fracture, ischemic stroke and non-variceal upper gastrointestinal bleeding, or those who underwent isolated cardiac valve procedure, isolated coronary artery bypass graft surgery, non-ruptured abdominal aortic aneurysm repair and interventions for the following tumors: colon, kidney, brain, lung, stomach, rectal, liver or pancreatic cancer. Main Outcome Measures: Condition-specific 30 day crude and risk-adjusted mortality rates. Results: A total of 808 280 admissions were reported from 844 institutions (median of 4 conditions evaluated per hospital; interquartile range 2-8). Volumes and outcome varied by clinical and surgical conditions across hospitals. Out of 153 pairs of different conditions, 41 were statistically significant in terms of concordance with crude mortality rates and 44 for their adjusted values. The hospital mean percentile rank for 30-day mortality, a composite measure that summarized the multiple indicators, increased significantly alongside number of conditions per hospital with a significant reduction of mortality when most of the studied conditions were treated in the same hospital. Conclusions: The variability in 30-day mortality rates at hospital level and the correlation between risk mortality rates suggest that there may be common hospital-wide factors influencing short term mortality. PMID- 27655790 TI - Effect of the medical insurance on the quality of care for Chinese patients with chronic heart failure. AB - Objective: To assess the effect of medical insurance on the quality of care for patients with chronic heart failure (CHF). Design: Seven quality indicators were used to assess the association between medical insurance and quality of care. Statistical analyses were conducted using multilevel logistic models for the total population and the subpopulation stratified by sex and age. Participants: In total, 1862 CHF patients who were admitted in 20 tertiary hospitals between 1 January 2009 and 31 October 2010. Results: Of 1862 patients, 53.8% patients had basic medical insurance and 26.9% patients paid the hospital costs by themselves. After adjusting for confounding factors, patients with New Rural Cooperative Medical Scheme (NRCMS) were more likely to receive warfarin (odds ratios [OR], 3.89; 95% confidence interval [CI], 1.08-13.99; P = 0.038), but less likely to receive aldosterone receptor antagonist (OR, 0.21; 95% CI, 0.08-0.56; P = 0.002) than patients without any medical insurance. Urban Employee Basic Medical Insurance (UEBMI) and NRCMS were associated with more use of discharge instructions ([OR, 3.54; 95% CI, 2.44-5.13; P < 0.001] and [OR, 2.09; 95% CI, 1.21-3.62; P = 0.009], respectively). After stratified by sex, male patients with UEBMI were more likely to receive the evaluation of left ventricular function than male patients without any medical insurance (OR, 1.78; 95% CI, 1.06-2.98; P = 0.029). Conclusions: UEBMI and NRCMS could increase the adherence to quality indicators of CHF to some extent. Improving the medical insurance system is expected to achieve equality in medical security and improve the quality of care for CHF patients. PMID- 27655791 TI - Patient satisfaction with ambulatory care in Germany: effects of patient- and medical practice-related factors. AB - Objective: The study aimed to illustrate the effect of the patients' sex, age, self-rated health and medical practice specialization on patient satisfaction. Design: Secondary analysis of patient survey data using multilevel analysis (generalized linear mixed model, medical practice as random effect) using a sequential modelling strategy. We examined the effects of the patients' sex, age, self-rated health and medical practice specialization on four patient satisfaction dimensions: medical practice organization, information, interaction, professional competence. Setting: The study was performed in 92 German medical practices providing ambulatory care in general medicine, internal medicine or gynaecology. Participants: In total, 9888 adult patients participated in a patient survey using the validated 'questionnaire on satisfaction with ambulatory care-quality from the patient perspective [ZAP]'. Main outcome measure(s): We calculated four models for each satisfaction dimension, revealing regression coefficients with 95% confidence intervals (CIs) for all independent variables, and using Wald Chi-Square statistic for each modelling step (model validity) and LR-Tests to compare the models of each step with the previous model. Results: The patients' sex and age had a weak effect (maximum regression coefficient 1.09, CI 0.39; 1.80), and the patients' self-rated health had the strongest positive effect (maximum regression coefficient 7.66, CI 6.69; 8.63) on satisfaction ratings. The effect of medical practice specialization was heterogeneous. Conclusions: All factors studied, specifically the patients' self-rated health, affected patient satisfaction. Adjustment should always be considered because it improves the comparability of patient satisfaction in medical practices with atypically varying patient populations and increases the acceptance of comparisons. PMID- 27655792 TI - Drug-dispensing problems community pharmacists face when patients are discharged from hospitals: a study about 537 prescriptions in Alsace. AB - Objectives: To identify both type and frequency of the challenges community pharmacists face when dispensing drugs from hospital discharge prescriptions, to describe the measures undertaken to resolve the issues at stake and to list their consequences. Design: We carried out an observational study in the community pharmacies of the French region of Alsace and asked the community pharmacy staff to review 537 hospital discharge prescriptions in 2013 using anonymous data collection forms. Setting and Participants: Nineteen community pharmacies. Main outcome measures: Number of patients informed about their medication (at hospital and/or community pharmacy), type and frequency of issues encountered during drug dispensing, type and frequency of measures undertaken to resolve the issues, type and frequency of the consequences regarding drug dispensing. Results: Community pharmacists faced 165 challenges from 145 hospital discharge prescriptions (i.e. 27.5% out of 528 analysed prescriptions), mostly correlated to the quality of the prescriptions (n = 100, 60.6%) or to logistical matters (n = 54, 32.7%). A mere 36.8% of the patients received information pertaining to their medication while being hospitalized. Of note, 40.5% of the prescriptions were delivered to pharmacies within 2 days following the patients' discharge. In order to resolve the different issues preventing drugs from being dispensed (n = 33/145 prescriptions), pharmacists sought information, mainly from patients, colleagues and hospital prescribers. The pharmacists were able to dispense all the drugs prescribed in 138 out of 145 cases (95.2%). Conclusions: This study highlighted the challenges encountered by community pharmacists and their significant contribution to the continuity of care upon patients being discharged from hospitals. PMID- 27655793 TI - Content validity of a health science evidence-based practice questionnaire (HS EBP) with a web-based modified Delphi approach. AB - Objective: To develop a tool for measuring evidence-based practice (EBP) and to evaluate its content validity by Delphi technique. A five-factor/dimensions latent structure for the EBP construct was defined a priori and operationalized. Design: Online Delphi technique. Setting and Participants: A group of 32 national EBP experts from different health professions. Intervention: The experts rated the initial questionnaire items according to adequacy and relevance criteria using four-point Likert scales and including open fields for suggestions, with basic and supplementary criteria consensus established a priori. Main Outcome Measure: Level of consensus in the Content Validity Index Item. Results: An EBP construct solution was designed with the elements that constitute the operationalization proposal of the EBP. This initial version consisted of 76 items, whereas the version arising from the Delphi study was made up of 73 items. In the first round, 13 items did not reach the minimum level of consensus, and 12 of these were reformulated. Three additional items were removed in the second round. Conclusions: A new psychometric tool forms measuring EBP with a five factor structure, and 73 items obtained adequate content validity evidence based on expert opinion. PMID- 27655795 TI - The differential effects of azithromycin on the airway epithelium in vitro and in vivo. AB - Macrolides including azithromycin (AZM) can improve clinical symptoms in asthma regardless of infection status. The mechanisms underlying these beneficial effects are yet to be elucidated. The aim of this study was to determine the effect of AZM on the airway epithelial barrier both in an in vitro model and in patients with asthma. Primary human bronchial epithelial cells (HBEC) were grown at air liquid interface (ALI) and challenged using lipopolysaccharides from Pseudomonas aeruginosa AZM was added at various stages and barrier integrity assessed using transepithelial electrical resistance (TEER) and permeability to FITC-dextran. MMP-9 levels were measured using ELISA AZM enhanced barrier integrity (TEER/FITC-dextran), increased thickness, suppressed mucin production, and MMP-9 release during the formation of a normal epithelial barrier in vitro. MMP-9 levels inversely correlated with TEER AZM also enhanced maintenance of the barrier and facilitated repair post-LPS challenge. To provide translation of our findings, 10 patients with moderate-severe asthma were recruited and received 250 mg AZM o.d for 6 weeks. Bronchial biopsies taken pre- and post-AZM treatment did not show evidence of increased epithelial barrier thickness or decreased mucin production. Similarly, bronchial wash samples did not show reduced MMP-9 levels. Overall, our data show that AZM can significantly improve the development of a normal bronchial epithelial barrier in vitro, mimicking reepithelization postinjury. AZM also suppressed MMP-9 release which correlated with barrier integrity, suggesting a putative mechanism. However, these effects were not observed in biopsy samples from asthma patients treated with AZM, possibly due to small sample size. PMID- 27655796 TI - Thyroid hormone treatment decreases hepatic glucose production and renal reabsorption of glucose in alloxan-induced diabetic Wistar rats. AB - The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Adult Male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 MUg/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats. PMID- 27655794 TI - CC-chemokine receptor 7 (CCR7) deficiency alters adipose tissue leukocyte populations in mice. AB - The mechanism by which macrophages and other immune cells accumulate in adipose tissue (AT) has been an area of intense investigation over the past decade. Several different chemokines and their cognate receptors have been studied for their role as chemoattractants in promoting recruitment of immune cells to AT However, it is also possible that chemoattractants known to promote clearance of immune cells from tissues to regional lymph nodes might be a critical component to overall AT immune homeostasis. In this study, we evaluated whether CCR7 influences AT macrophage (ATM) or T-cell (ATT) accumulation. CCR7-/- and littermate wild-type (WT) mice were placed on low-fat diet (LFD) or high-fat diet (HFD) for 16 weeks. CCR7 deficiency did not impact HFD-induced weight gain, hepatic steatosis, or glucose intolerance. Although lean CCR7-/- mice had an increased proportion of alternatively activated ATMs, there were no differences in ATM accumulation or polarization between HFD-fed CCR7-/- mice and their WT counterparts. However, CCR7 deficiency did lead to the preferential accumulation of CD8+ ATT cells, which was further exacerbated by HFD feeding. Finally, expression of inflammatory cytokines/chemokines, such as Tnf, Il6, Il1beta, Ccl2, and Ccl3, was equally elevated in AT by HFD feeding in CCR7-/- and WT mice, while Ifng and Il18 were elevated by HFD feeding in CCR7-/- but not in WT mice. Together, these data suggest that CCR7 plays a role in CD8+ATT cell egress, but does not influence ATM accumulation or the metabolic impact of diet-induced obesity. PMID- 27655798 TI - The Mayak Worker Dosimetry System (MWDS-2013): Uncertainty in the Measurement of Pu Activity in a 24-Hour Urine Sample of a Typical Mayak PA Worker. AB - In the Mayak Worker Dosimetry System (MWDS-2013), intakes of plutonium and organ doses are assessed on the basis of measurements made on the plutonium content of 56 400 urine samples. Altogether, there were urine bioassays for 7591 (29%) of the 25 757 cohort members who were employed any time at Mayak between 1948 and 1982. These measurements are subject to uncertainty due to many factors (e.g. whether or not creatinine is measured, the volume of the sample, whether diethylenetriaminepentaacetic acid was administered, etc.) and this uncertainty will affect not only the uncertainty in the estimated doses, but also the values of the doses themselves. Therefore, it is important for the estimated uncertainty to be as accurate as possible. The input to the dose calculation requires an estimate of the plutonium activity in a true 24-hour sample. The uncertainty in this activity is approximated by a lognormal distribution. The aim of this paper is to describe and justify how the parameters of this lognormal distribution are derived from the raw data. Histograms of the distribution of sample volumes are given for both sexes. The method of calculation of the decision threshold and relative standard uncertainty (RSU) of a measurement result for Pu activity in a worker's urine sample is shown. Diagrams of correlation between Pu activity in collected urine and its RSU are given. PMID- 27655797 TI - Neurons in primary visual cortex represent distribution of luminance. AB - To efficiently detect a wide range of light-intensity changes, visual neurons must adapt to ambient luminance. However, how neurons in the primary visual cortex (V1) code the distribution of luminance remains unknown. We designed stimuli that represent rapid changes in luminance under different luminance distributions and investigated V1 neuron responses to these novel stimuli. We demonstrate that V1 neurons represent luminance changes by dynamically adjusting their responses when the luminance distribution changes. Many cells (35%) detected luminance changes by responding to dark stimuli when the distribution was dominated by bright stimuli, bright stimuli when dominated by dark stimuli, and both dark and bright stimuli when dominated by intermediate luminance stimuli; 13% of cells signaled the mean luminance that was varied with different distributions; the remaining 52% of cells gradually shifted the responses that were most sensitive to luminance changes when the luminance distribution varied. The remarkable response changes of the former two cell groups suggest their crucial roles in detecting luminance changes. These response characteristics demonstrate that V1 neurons are not only sensitive to luminance change, but also luminance distribution change. They encode luminance changes according to the luminance distribution. Mean cells represent the prevailing luminance and reversal cells represent the salient stimuli in the environment. PMID- 27655799 TI - Radionuclides Content in Pasteurized Cow Milk: Dose Estimation. AB - Results from the radiological monitoring of 46 pasteurized cow milks for the period of 2011-2015 are presented. The activity of 137Cs, 90Sr, 226Ra, 40K, 210Pb, 232Th and natural U was determined by gamma spectrometry for gamma emitters and by radiochemical separation for 90Sr. The maximum obtained results are 0.449 +/- 0.016 Bq/l (137Cs), 0.105 +/- 0.020 Bq/l (90Sr), 1.63 +/- 0.16 Bq/l (226Ra), 53.1 +/- 1.6 Bq/l (40K), 1.01 +/- 0.30 Bq/l (210Pb), 0.05 +/- 0.07 Bq/l (232Th) and 0.14 +/- 0.12 mg/l (natural U). Annual Effective Dose from the ingestion of above-mentioned radionuclides was estimated on the basis of the consumption for adults and children (1-2 y) applying two models-realistic and conservative. The values for the Ingestion Dose vary from 0.02 mSv/y to 0.05 mSv/y (adults, realistic model) and from 0.06 to 0.15 mSv/y (adults) and from 0.15 to 0.87 mSv/y (children 1-2 y old) from conservative model. For bought models, the main contribution to the Ingestion Dose, instead of 40K, is due to the 210Pb and 226Ra. Three hypotheses are given for the 226Ra content in pasteurized cow milk. The received results demonstrate the need of determination of artificial and natural radionuclides in cow milk. PMID- 27655800 TI - New Correction Factors Based on Seasonal Variability of Outdoor Temperature for Estimating Annual Radon Concentrations in UK. AB - Indoor radon concentrations generally vary with season. Radon gas enters buildings from beneath due to a small air pressure difference between the inside of a house and outdoors. This underpressure which draws soil gas including radon into the house depends on the difference between the indoor and outdoor temperatures. The variation in a typical house in UK showed that the mean indoor radon concentration reaches a maximum in January and a minimum in July. Sine functions were used to model the indoor radon data and monthly average outdoor temperatures, covering the period between 2005 and 2014. The analysis showed a strong negative correlation between the modelled indoor radon data and outdoor temperature. This correlation was used to calculate new correction factors that could be used for estimation of annual radon concentration in UK homes. The comparison between the results obtained with the new correction factors and the previously published correction factors showed that the new correction factors perform consistently better on the selected data sets. PMID- 27655801 TI - Development of a Multi-Sensitive Element Passive Dosemeter Based on OSL Technology. AB - In 2012 the IEC 62387-1:2007 (IEC.Radiation protection instrumentation-Passive integrating dosimetry systems for environmental and personal monitoring Part 1: General characteristics and performance requirements. IEC 62387-1:2007 (2007)) standard has been transposed by the CENELEC into a European version (EN 62387 1:2012 (Instrumentation pour la radioprotection-Systemes dosimetriques integres passifs pour la surveillance de l'environnement et de l'individu-Partie 1 : Caracteristiques generales et exigences de fonctionnement. NF EN 62387-1:2012 (2012))). In order to meet with this standard, LANDAUER has developed, by Monte Carlo method, a new dosemeter based on the Optically Stimulated Luminescence technology with Al2O3:C crystals and a new type of dose estimation algorithm. This dosemeter aims at measuring dose equivalent generated from exposure to X rays, gamma-rays and beta-rays. According to the standard, it has undergone a comprehensive set of tests that have been performed by the LNE-LNHB, the French national metrology laboratory responsible for the fields of ionizing radiation (Bordy, J.-M. Evaluation of the algorithms used to derive the dose from the raw readings of the Inlight LDR holder case type GN of Landauer. LNHB technical note, LNHB 2013-46 (2013)). In the end, the dosemeter was declared compliant with the EN 62387-1:2012 standard. PMID- 27655802 TI - SPECTRAL CORRECTION FACTORS FOR CONVENTIONAL NEUTRON DOSE METERS USED IN HIGH ENERGY NEUTRON ENVIRONMENTS-IMPROVED AND EXTENDED RESULTS BASED ON A COMPLETE SURVEY OF ALL NEUTRON SPECTRA IN IAEA-TRS-403. AB - This paper presents improved and extended results of our previous study on corrections for conventional neutron dose meters used in environments with high energy neutrons (En > 10 MeV). Conventional moderated-type neutron dose meters tend to underestimate the dose contribution of high-energy neutrons because of the opposite trends of dose conversion coefficients and detection efficiencies as the neutron energy increases. A practical correction scheme was proposed based on analysis of hundreds of neutron spectra in the IAEA-TRS-403 report. By comparing 252Cf-calibrated dose responses with reference values derived from fluence-to dose conversion coefficients, this study provides recommendations for neutron field characterization and the corresponding dose correction factors. Further sensitivity studies confirm the appropriateness of the proposed scheme and indicate that (1) the spectral correction factors are nearly independent of the selection of three commonly used calibration sources: 252Cf, 241Am-Be and 239Pu Be; (2) the derived correction factors for Bonner spheres of various sizes (6" 9") are similar in trend and (3) practical high-energy neutron indexes based on measurements can be established to facilitate the application of these correction factors in workplaces. PMID- 27655803 TI - Estimating the Internal Dose for 131I Production Workers From Air Sampling Method. AB - Besides the most common methods of internal dose assessment from inhaled 131I, that are thyroid monitoring and urine analysis, air sampling is a possible way but rarely used for dose estimate. This study aimed to focus on the utilisation of portable air sampler to estimate the internal dose for workers working at 131I production facility. In addition, internal dose estimated from urine analysis at the same time was carried out for comparison. Based on this research, it was found that air monitoring can be done efficiently as urine monitoring if the following conditions are met: (1) the indoor areas are not large, (2) sampling sites need to be placed as near breathing zone as possible and (3) the time-micro environment patterns of monitored workers are collected carefully. PMID- 27655804 TI - The Mayak Worker Dosimetry System (MWDS-2013): How to Reduce Hyper-Realisations to Realisations. AB - Two important aspects in which the MWDS-2013 output (absorbed dose to organs calculated in each calendar year) differs from previous data bases (MWDS-2008 and DOSES-2005) are that they have been designed to (a) deal explicitly with uncertainties in model parameters, and (b) differentiate parameters that are considered to be shared (unknown, but having the same value for all workers) and unshared (unknown, but having different values between workers). A multiple realisation approach is used to preserve information on the effects of shared and unshared parameters both for internal and external doses. Previously, a single realisation (a set of organ doses: one for each worker in the cohort) was calculated using the best estimates of parameter values only. In MWDS-2013, a set of 1000 realisations is produced, to reflect the uncertainty in assumed model parameters: each realisation using a different set of parameter values. Within each realisation, shared parameter values are fixed throughout the cohort, while unshared parameters are allowed to vary between workers. One problem is that because the calculation of organ dose is Bayesian, the estimate for each organ dose is not just a single value, but is itself a distribution (hyper-dose). Technically, it is the probability density of dose given the sampled set of parameter values and given the data for that worker. Thus, in our case, the realisations consist not of single doses, but distributions of doses. The term hyper-realisation is used to differentiate this from the more conventional realisation. Although the multiple hyper-realisation in principle contains all of the necessary information on parameter uncertainty, including shared and unshared parameters, in order to make preliminary epidemiological analyses tractable, and also for consistency with the external doses, it was required to convert the hyper-realisations to realisations. The aim of this paper is to discuss the different approaches that were considered to do this, and to define the method that was eventually chosen. Single spot (point) estimates of dose (for each worker) were also calculated to support the epidemiological analysis. The different methods for obtaining these and the implications are also discussed. PMID- 27655805 TI - ANOVA model for network meta-analysis of diagnostic test accuracy data. AB - Procedures combining and summarising direct and indirect evidence from independent studies assessing the diagnostic accuracy of different tests for the same disease are referred to network meta-analysis. Network meta-analysis provides a unified inference framework and uses the data more efficiently. Nonetheless, handling the inherent correlation between sensitivity and specificity continues to be a statistical challenge. We developed an arm-based hierarchical model which expresses the logit transformed sensitivity and specificity as the sum of fixed effects for test, correlated study-effects to model the inherent correlation between sensitivity and specificity and a random error associated with various tests evaluated in a given study. We present the accuracy of 11 tests used to triage women with minor cervical lesions to detect cervical precancer. Finally, we compare the results with those from a contrast based model which expresses the linear predictor as a contrast to a comparator test. The proposed arm-based model is more appealing than the contrast-based model since the former permits more straightforward interpretation of the parameters, makes use of all available data yielding shorter credible intervals, and models more natural variance-covariance matrix structures. PMID- 27655806 TI - Inferring marginal association with paired and unpaired clustered data. AB - In the marginal analysis of clustered data, where the marginal distribution of interest is that of a typical observation within a typical cluster, analysis by reweighting has been introduced as a useful tool for estimating parameters of these marginal distributions. Such reweighting methods have foundation in within cluster resampling schemes that marginalize potential informativeness due to cluster size or within-cluster covariate distribution, to which reweighting methods are asymptotically equivalent. In this paper, we introduce a reweighting scheme for the marginal analysis of clustered data that generalizes prior reweighting methods, with a particular application to measuring bivariate correlation in unpaired clustered data, in which observations of two random variables are not naturally paired at the within-cluster level. We develop unpaired clustered data analogs of well-known product moment correlation coefficients (Pearson, Spearman, phi), as well as the polyserial coefficient for measuring correlation between one discrete and one continuous variable. We evaluate the performance of these coefficients via a simulation study and demonstrate their use by finding no statistically significant association between dental caries at an early age and dental fluorosis at age 13 using a large dental dataset. PMID- 27655808 TI - Colon Cancer Germline Genetics: The Unbelievable Year 1993 and Thereafter. PMID- 27655809 TI - The Role of CagA in the Gastric Biology of Helicobacter pylori. PMID- 27655811 TI - Errors in surgery. PMID- 27655810 TI - Gender differences in VO2 and HR kinetics at the onset of moderate and heavy exercise intensity in adolescents. AB - The majority of the studies on VO2 kinetics in pediatric populations investigated gender differences in prepubertal children during submaximal intensity exercise, but studies are lacking in adolescents. The purpose of this study was to test the hypothesis that gender differences exist in the VO2 and heart rate (HR) kinetic responses to moderate (M) and heavy (H) intensity exercise in adolescents. Twenty one healthy African-American adolescents (9 males, 15.8 +/- 1.1 year; 12 females, 15.7 +/- 1 year) performed constant work load exercise on a cycle ergometer at M and H. The VO2 kinetics of the male group was previously analyzed (Lai et al., Appl. Physiol. Nutr. Metab. 33:107-117, 2008b). For both genders, VO2 and HR kinetics were described with a single exponential at M and a double exponential at H. The fundamental time constant (tau1) of VO2 was significantly higher in female than male at M (45 +/- 7 vs. 36 +/- 11 sec, P < 0.01) and H (41 +/- 8 vs. 29 +/- 9 sec, P < 0.01), respectively. The functional gain (G1) was not statistically different between gender at M and statistically higher in females than males at H: 9.7 +/- 1.2 versus 10.9 +/- 1.3 mL min-1 W-1, respectively. The amplitude of the slow component was not significantly different between genders. The HR kinetics were significantly (tau1, P < 0.01) slower in females than males at M (61 +/- 16 sec vs. 45 +/- 20 sec, P < 0.01) and H (42 +/- 10 sec vs. 30 +/- 8 sec, P = 0.03). The G1 of HR was higher in females than males at M: 0.53 +/- 0.11 versus 0.98 +/- 0.2 bpm W-1 and H: 0.40 +/- 0.11 versus 0.73 +/- 0.23 bpm W 1, respectively. Gender differences in the VO2 and HR kinetics suggest that oxygen delivery and utilization kinetics of female adolescents differ from those in male adolescents. PMID- 27655812 TI - Commentaries on Clinical results of releasing the entire A2 pulley after flexor tendon repair in zone 2C. K. Moriya, T. Yoshizu, N. Tsubokawa, H. Narisawa, K. Hara and Y. Maki. J Hand Surg Eur. 2016, 41: 822-28. PMID- 27655813 TI - Re: Agrawal AK, Mat Jais IS, Chew EM, Yam AKT, Tay SC. Biomechanical investigation of 'figure of 8' flexor tendon repair techniques. J Hand Surg Eur. 2016, 41: 815-21. PMID- 27655816 TI - A sparsity-controlled vector autoregressive model. AB - Vector autoregressive (VAR) models constitute a powerful and well studied tool to analyze multivariate time series. Since sparseness, crucial to identify and visualize joint dependencies and relevant causalities, is not expected to happen in the standard VAR model, several sparse variants have been introduced in the literature. However, in some cases it might be of interest to control some dimensions of the sparsity, as e.g. the number of causal features allowed in the prediction. To authors extent none of the existent methods endows the user with full control over the different aspects of the sparsity of the solution. In this article, we propose a versatile sparsity-controlled VAR model which enables a proper visualization of potential causalities while allows the user to control different dimensions of the sparsity if she holds some preferences regarding the sparsity of the outcome. The model coefficients are found as the solution to an optimization problem, solvable by standard numerical optimization routines. The tests performed on both simulated and real-life time series show that our approach may outperform a greedy algorithm and different Lasso approaches in terms of prediction errors and sparsity. PMID- 27655817 TI - Inference for the difference in the area under the ROC curve derived from nested binary regression models. AB - The area under the curve (AUC) statistic is a common measure of model performance in a binary regression model. Nested models are used to ascertain whether the AUC statistic increases when new factors enter the model. The regression coefficient estimates used in the AUC statistics are computed using the maximum rank correlation methodology. Typically, inference for the difference in AUC statistics from nested models is derived under asymptotic normality. In this work, it is demonstrated that the asymptotic normality is true only when at least one of the new factors is associated with the binary outcome. When none of the new factors are associated with the binary outcome, the asymptotic distribution for the difference in AUC statistics is a linear combination of chi-square random variables. Further, when at least one new factor is associated with the outcome and the population difference is small, a variance stabilizing reparameterization improves the asymptotic normality of the AUC difference statistic. A confidence interval using this reparameterization is developed and simulations are generated to determine their coverage properties. The derived confidence interval provides information on the magnitude of the added value of new factors and enables investigators to weigh the size of the improvement against potential costs associated with the new factors. A pancreatic cancer data example is used to illustrate this approach. PMID- 27655818 TI - Lissaman, Shollenberger and formation flight in birds. PMID- 27655819 TI - Mechanosensory signaling as a potential mode of communication during social interactions in fishes. AB - Signals produced during social interactions convey crucial information about the sender's identity, quality, reproductive state and social status. Fishes can detect near-body water movements via the mechanosensory lateral line system, and this sense is used during several common fish behaviors, such as schooling, rheotaxis and predator-prey interactions. In addition, many fish behaviors, such as aggressive lateral displays and reproductive body quivers, involve fin and body motions that generate water movements that can be detected by the lateral line system of nearby fish. This mechanosensory system is well studied for its role in obstacle avoidance and detection of inadvertent hydrodynamic cues generated during schooling and predator-prey interactions; however, little research has focused on the role of mechanosensory communication during social interactions. Here, we summarize the current literature on the use of mechanosensation-mediated behaviors during agonistic and reproductive encounters, as well as during parental care. Based on these studies, we hypothesize that mechanosensory signaling is an important but often overlooked mode of communication during conspecific social interactions in many fish species, and we highlight its importance during multimodal communication. Finally, we suggest potential avenues of future research that would allow us to better understand the role of mechanosensation in fish communication. PMID- 27655820 TI - Photoreception and vision in the ultraviolet. AB - Ultraviolet (UV) light occupies the spectral range of wavelengths slightly shorter than those visible to humans. Because of its shorter wavelength, it is more energetic (and potentially more photodamaging) than 'visible light', and it is scattered more efficiently in air and water. Until 1990, only a few animals were recognized as being sensitive to UV light, but we now know that a great diversity, possibly even the majority, of animal species can visually detect and respond to it. Here, we discuss the history of research on biological UV photosensitivity and review current major research trends in this field. Some animals use their UV photoreceptors to control simple, innate behaviors, but most incorporate their UV receptors into their general sense of vision. They not only detect UV light but recognize it as a separate color in light fields, on natural objects or living organisms, or in signals displayed by conspecifics. UV visual pigments are based on opsins, the same family of proteins that are used to detect light in conventional photoreceptors. Despite some interesting exceptions, most animal species have a single photoreceptor class devoted to the UV. The roles of UV in vision are manifold, from guiding navigation and orientation behavior, to detecting food and potential predators, to supporting high-level tasks such as mate assessment and intraspecific communication. Our current understanding of UV vision is restricted almost entirely to two phyla: arthropods and chordates (specifically, vertebrates), so there is much comparative work to be done. PMID- 27655821 TI - Shoaling reduces metabolic rate in a gregarious coral reef fish species. AB - Many animals live in groups because of the potential benefits associated with defense and foraging. Group living may also induce a 'calming effect' on individuals, reducing overall metabolic demand. This effect could occur by minimising the need for individual vigilance and reducing stress through social buffering. However, this effect has proved difficult to quantify. We examined the effect of shoaling on metabolism and body condition in the gregarious damselfish Chromis viridis Using a novel respirometry methodology for social species, we found that the presence of shoal-mate visual and olfactory cues led to a reduction in the minimum metabolic rate of individuals. Fish held in isolation for 1 week also exhibited a reduction in body condition when compared with those held in shoals. These results indicate that social isolation as a result of environmental disturbance could have physiological consequences for gregarious species. PMID- 27655822 TI - Smart Mechanical Dipole: a device for the measurement of sphere motion in behavioral and neurophysiological experiments. AB - Fluid motion and pressure fields induced by vibrating spheres are frequently used to investigate the function of biological mechanosensory systems and artificial sensors. The calibration of the sphere motion amplitude (displacement, velocity, acceleration), time course and vibration direction often demands expensive equipment. To mitigate this requirement, we have developed a high-quality, low cost device that we term a 'Smart Mechanical Dipole'. It provides real-time measurement of sphere acceleration along three axes and can be used to obtain an accurate stimulation trace. We applied digital filtering to equalize the frequency response of the vibrating sphere, which also reduced unwanted amplitude and frequency changes in the hydrodynamic signal. In addition, we show that the angular orientation of the rod to which the sphere was attached, i.e. axial versus transverse, but not the immersion depth of the sphere affected sphere vibration behavior. PMID- 27655823 TI - Navigating under sea ice promotes rapid maturation of diving physiology and performance in beluga whales. AB - Little is known about the postnatal development of the physiological characteristics that support breath-hold in cetaceans, despite their need to swim and dive at birth. Arctic species have the additional demand of avoiding entrapment while navigating under sea ice, where breathing holes are patchily distributed and ephemeral. This is the first investigation of the ontogeny of the biochemistry of the locomotor muscle in a year-round Arctic-dwelling cetacean (beluga whale, Delphinapterus leucas). Compared with what we know about other cetaceans, belugas are born with high myoglobin content (1.56+/-0.02 g 100 g-1 wet muscle mass, N=2) that matures rapidly. Myoglobin increased by 452% during the first year after birth and achieved adult levels (6.91+/-0.35 g 100 g-1 wet muscle mass, N=9) by 14 months postpartum. Buffering capacity was 48.88+/-0.69 slykes (N=2) at birth; adult levels (84.31+/-1.38 slykes, N=9) were also achieved by 14 months postpartum. As the oxygen stores matured, calculated aerobic dive limit more than doubled over the first year of life, undoubtedly facilitating the movements of calves under sea ice. Nonetheless, small body size theoretically continues to constrain the diving ability of newly weaned 2 year olds, as they only had 74% and 69% of the aerobic breath-hold capacity of larger adult female and male counterparts. These assessments enhance our knowledge of the biology of cetaceans and provide insight into age-specific flexibility to alter underwater behaviors, as may be required with the ongoing alterations in the Arctic marine ecosystem associated with climate change and increased anthropogenic activities. PMID- 27655824 TI - Morphine addiction in ants: a new model for self-administration and neurochemical analysis. AB - Conventional definitions of drug addiction are focused on characterizing the neurophysiological and behavioral responses of mammals. Although mammalian models have been invaluable in studying specific and complex aspects of addiction, invertebrate systems have proven advantageous in investigating how drugs of abuse corrupt the most basic motivational and neurochemical systems. It has recently been shown that invertebrates and mammals have remarkable similarities in their behavioral and neurochemical responses to drugs of abuse. However, until now only mammals have demonstrated drug seeking and self-administration without the concurrent presence of a natural reward, e.g. sucrose. Using a sucrose-fading paradigm, followed by a two-dish choice test, we establish ants as an invertebrate model of opioid addiction. The ant species Camponotus floridanus actively seeks and self-administers morphine even in the absence of caloric value or additional natural reward. Using HPLC equipped with electrochemical detection, the neurochemicals serotonin, octopamine and dopamine were identified and subsequently quantified, establishing the concurrent neurochemical response to the opioid morphine within the invertebrate brain. With this study, we demonstrate dopamine to be governing opioid addiction in the brains of ants. Thus, this study establishes ants as the first non-mammalian model of self administration that is truly analogous to mammals. PMID- 27655825 TI - Automatic control: the vertebral column of dogfish sharks behaves as a continuously variable transmission with smoothly shifting functions. AB - During swimming in dogfish sharks, Squalus acanthias, both the intervertebral joints and the vertebral centra undergo significant strain. To investigate this system, unique among vertebrates, we cyclically bent isolated segments of 10 vertebrae and nine joints. For the first time in the biomechanics of fish vertebral columns, we simultaneously characterized non-linear elasticity and viscosity throughout the bending oscillation, extending recently proposed techniques for large-amplitude oscillatory shear (LAOS) characterization to large amplitude oscillatory bending (LAOB). The vertebral column segments behave as non linear viscoelastic springs. Elastic properties dominate for all frequencies and curvatures tested, increasing as either variable increases. Non-linearities within a bending cycle are most in evidence at the highest frequency, 2.0 Hz, and curvature, 5 m-1 Viscous bending properties are greatest at low frequencies and high curvatures, with non-linear effects occurring at all frequencies and curvatures. The range of mechanical behaviors includes that of springs and brakes, with smooth transitions between them that allow for continuously variable power transmission by the vertebral column to assist in the mechanics of undulatory propulsion. PMID- 27655826 TI - Spatial learning in the cuttlefish Sepia officinalis: preference for vertical over horizontal information. AB - The world is three-dimensional; hence, even surface-bound animals need to learn vertical spatial information. Separate encoding of vertical and horizontal spatial information seems to be the common strategy regardless of the locomotory style of animals. However, a difference seems to exist in the way freely moving species, such as fish, learn and integrate spatial information as opposed to surface-bound species, which prioritize the horizontal dimension and encode it with a higher resolution. Thus, the locomotory style of an animal may shape how spatial information is learned and prioritized. An alternative hypothesis relates the preference for vertical information to the ability to sense hydrostatic pressure, a prominent cue unique to this dimension. Cuttlefish are mostly benthic animals, but they can move freely in a volume. Therefore, they present an optimal model to examine these hypotheses. We tested whether cuttlefish could separately recall the vertical and horizontal components of a learned two-dimensional target, and whether they have a preference for vertical or horizontal information. Sepia officinalis cuttlefish were trained to select one of two visual cues set along a 45 deg diagonal. The animals were then tested with the two visual cues arranged in a horizontal, vertical or opposite 45 deg configuration. We found that cuttlefish use vertical and horizontal spatial cues separately, and that they prefer vertical information to horizontal information. We propose that, as in fish, the availability of hydrostatic pressure, combined with the ecological value of vertical movements, determines the importance of vertical information. PMID- 27655827 TI - Correction: Body density and diving gas volume of the northern bottlenose whale (Hyperoodon ampullatus). PMID- 27655828 TI - Correction: Programming of the hypothalamic-pituitary-interrenal axis by maternal social status in zebrafish (Danio rerio). PMID- 27655829 TI - The boldness of philanthropists. PMID- 27655830 TI - Traumatic Avulsion of the Serratus Anterior Muscle in a Collegiate Rower: A Case Report. AB - A 19-year-old female collegiate rower presented with a new, painful mass along her right anterolateral chest wall after competition. The patient was diagnosed with a rupture of the serratus anterior muscle from its costal attachments, as confirmed by magnetic resonance imaging. The patient fully recovered after a period of rest followed by a graduated 2-month physical therapy regimen consisting of stretching and scapulothoracic and core strengthening. A traumatic rupture of the serratus anterior muscle should be suspected in athletes who present with a painful chest wall mass after exertion of large forces through the scapulothoracic region. Athletes can return to play after nonoperative management. PMID- 27655831 TI - Can vestibular rehabilitation exercises help patients with concussion? A systematic review of efficacy, prescription and progression patterns. AB - OBJECTIVE: Concussion symptoms normally resolve within 7-10 days but vertigo, dizziness and balance dysfunction persist in 10-30% of cases causing significant morbidity. This study systematically evaluated the evidence supporting the efficacy, prescription and progression patterns of vestibular rehabilitation therapy (VRT) in patients with concussion. DESIGN: Systematic Review, guided by PRISMA guidelines and presenting a best evidence synthesis. DATA SOURCES: Electronic databases PubMed (1949 to May 2015), CINAHL (1982 to May 2015), EMBASE (1947 to May 2015), SPORTDiscus (1985 to May 2015), Web of Science (1945 to May 2015) and PEDRO (1999 to May 2015), supplemented by manual searches and grey literature. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Article or abstract of original research, population of patients with concussion/mild traumatic brain injury (mTBI) with vestibular symptoms, interventions detailing VRT, measurement of outcomes pre-VRT/post-VRT. Study type was not specified. RESULTS: Following a double review of abstract and full-text articles, 10 studies met the inclusion criteria: randomised controlled trial (n=2), uncontrolled studies (n=3) and case studies (n=5). 4 studies evaluated VRT as a single intervention. 6 studies incorporated VRT in multimodal interventions (including manual therapy, strength training, occupational tasks, counselling or medication). 9 studies reported improvement in outcomes but level I evidence from only 1 study was found that demonstrated increased rates (OR 3.91; 95% CI 1.34 to 11.34; p=0.002) of medical clearance for return to sport within 8 weeks, when VRT (combined with cervical therapy) was compared with usual care. Heterogeneity in study type and outcomes precluded meta-analysis. Habituation and adaptation exercises were employed in 8 studies and balance exercises in 9 studies. Prescription and progression patterns lacked standardisation. CONCLUSIONS: Current evidence for optimal prescription and efficacy of VRT in patients with mTBI/concussion is limited. Available evidence, although weak, shows promise in this population. Further high-level studies evaluating the effects of VRT in patients with mTBI/concussion with vestibular and/or balance dysfunction are required. PMID- 27655832 TI - The glucose 6-phosphate shunt around the Calvin-Benson cycle. PMID- 27655833 TI - Novel Helicobacter species H.japonicum isolated from laboratory mice from Japan induces typhlocolitis and lower bowel carcinoma in C57BL/129 IL10-/- mice. AB - A novel Helicobacter species Helicobacter japonicum was isolated from the stomach and intestines of clinically normal mice received from three institutes from Japan. The novel Helicobacter sp. was microaerobic, grew at 37 degrees C and 42 degrees C, was catalase and oxidase positive, but urease negative. It is most closely related to the 16S rRNA gene of H.muridarum (98.6%); to the 23S rRNA gene of H.hepaticus (97.9%); to the hsp60 gene of H.typhlonius (87%). The novel Helicobacter sp. has in vitro cytolethal distending toxin (CDT) activity; its cdtB gene sequence has 83.8% identity with that of H.hepaticus The whole genome sequence of H.japonicum MIT 01-6451 has a 2.06-Mb genome length with a 37.5% G + C content. When the organism was inoculated into C57BL/129 IL10-/- mice, it was cultured from the stomach, colon and cecum of infected mice at 6 and 10 weeks post-infection. The cecum had the highest H.japonicum colonization levels by quantitative PCR. The histopathology of the lower bowel was characterized by moderate to severe inflammation, mild edema, epithelial defects, mild to severe hyperplasia, dysplasia and carcinoma. Inflammatory cytokines IFNgamma, TNFalpha and IL17a, as well as iNOS were significantly upregulated in the cecal tissue of infected mice. These results demonstrate that the novel H.japonicum can induce inflammatory bowel disease and carcinoma in IL10-/- mice and highlights the importance of identifying novel Helicobacter spp. especially when they are introduced from outside mouse colonies from different geographic locations. PMID- 27655834 TI - Prevention of DNA damage in Barrett's esophageal cells exposed to acidic bile salts. AB - Esophageal adenocarcinoma (EA) is one of the fastest rising tumors in the USA. The major risk factor for EA is gastroesophageal reflux disease (GERD). During GERD, esophageal cells are exposed to refluxate which contains gastric acid frequently mixed with duodenal bile. This may lead to mucosal injury and Barrett's metaplasia (BE) that are important factors contributing to development of EA. In this study, we investigated DNA damage in BE cells exposed to acidic bile salts and explored for potential protective strategies. Exposure of BE cells to acidic bile salts led to significant DNA damage, which in turn, was due to generation of reactive oxygen species (ROS). We found that acidic bile salts induce a rapid increase in superoxide radicals and hydrogen peroxide, which were determined using electron paramagnetic resonance spectroscopy and Amplex Red assay. Analyzing a panel of natural antioxidants, we identified apocynin to be the most effective in protecting esophageal cells from DNA damage induced by acidic bile salts. Mechanistic analyses showed that apocynin inhibited ROS generation and increases the DNA repair capacity of BE cells. We identified BRCA1 and p73 proteins as apocynin targets. Downregulation of p73 inhibited the protective effect of apocynin. Taken together, our results suggest potential application of natural compounds such as apocynin for prevention of reflux induced DNA damage and GERD-associated tumorigenesis. PMID- 27655836 TI - Diagnosis and Management of a Pancreaticopleural Fistula in a Patient with AIDS and a Large Pleural Effusion. AB - Pleural effusions typically present with nonspecific pulmonary complaints in the setting of either acute or chronic diseases. In the general population, these illnesses include congestive heart failure, infection, and malignancy. However, in people living with HIV/AIDS (PLWHA), pleural effusions often result from opportunistic infections and AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma. Since the introduction of highly active antiretroviral therapy, there has been a decline in the frequency of AIDS-defining opportunistic infections and AIDS-defining cancers and an increase in certain non-AIDS-defining malignancies including lung cancer. Throughout this period, longer life expectancy in PLWHA has contributed to an increased risk of those chronic diseases that can result in pleural effusions. This case describes an HIV infected man who was an active cigarette smoker and alcoholic and who presented with a large pleural effusion of uncertain etiology. The authors review several important noncardiac risk factors associated with pleural effusions in PLWHA. The authors also emphasize the importance of obtaining a detailed medical history and the use of appropriate imaging and laboratory tests in order to identify an underlying cause and to provide optimal treatment. PMID- 27655837 TI - Eggs or peanuts in early infant diet may cut allergy risk. PMID- 27655835 TI - HIV Stigma: Perspectives from Kenyan Child Caregivers and Adolescents Living with HIV. AB - Stigma shapes all aspects of HIV prevention and treatment, yet there are limited data on how HIV-infected youth and their families are affected by stigma in sub Saharan Africa. The authors conducted a qualitative study using focus group discussions among 39 HIV-infected adolescents receiving care at HIV clinics in western Kenya and 53 caregivers of HIV-infected children. Participants felt that while knowledge and access to treatment were increasing, many community members still held negative and inaccurate views about HIV, including associating it with immorality and believing in transmission by casual interactions. Stigma was closely related to a loss of social and economic support but also included internalized negative feelings about oneself. Participants identified treatment related impacts of stigma, including nonadherence, nondisclosure of status to child or others, and increased mental health problems. Qualitative inquiry also provided insights into how to measure and reduce stigma among affected individuals and families. PMID- 27655838 TI - An unusual initial manifestation of acute myeloid leukemia. AB - Leukemia cutis is seen in around 20% of acute monocytic leukemia. They usually present as papules or nodules or infiltrated plaques but ulceration is uncommon. A 28-year-old female presented with multiple painless indurated genital ulcers of three weeks' duration with low-grade fever, gum hyperplasia, and generalized lymphadenopathy. Tissue smear from the edge of the ulcer showed atypical monocytes suggestive of leukemic infiltrate which was further confirmed by peripheral smear and bone marrow aspirate. Herein, we report a case of acute monocytic leukemia (AML) with leukemia cutis presenting initially with genital ulcers simulating chancre. PMID- 27655839 TI - Dietary supplement interactions with antiretrovirals: a systematic review. AB - Many patients who take antiretroviral drugs also take alternative therapies including dietary supplements. Some drug-supplement combinations may result in clinically meaningful interactions. We aimed to investigate the evidence for dietary supplement interactions with antiretrovirals. A systematic review was conducted using multiple resources including PubMed, Natural Medicine Comprehensive Database, The Review of Natural Products, and Google Scholar. All human studies or case reports evaluating an interaction between a dietary supplement and an antiretroviral were selected for inclusion. Twenty-eight pharmacokinetic studies and case-series/case reports were selected for inclusion. Calcium carbonate, ferrous fumarate, some forms of ginkgo, some forms of garlic, some forms of milk thistle, St. John's wort, vitamin C, zinc sulfate, and multivitamins were all found to significantly decrease the levels of selected antiretrovirals and should be avoided in patients taking these antiretrovirals. Cat's claw and evening primrose oil were found to significantly increase the levels of antiretrovirals and patients should be monitored for adverse effects while taking these dietary supplements with antiretrovirals. This systematic review shows the importance of screening all human immunodeficiency virus patients for dietary supplement use to prevent treatment failure or adverse effects related to an interaction. PMID- 27655840 TI - A Role for TIC55 as a Hydroxylase of Phyllobilins, the Products of Chlorophyll Breakdown during Plant Senescence. AB - Chlorophyll degradation is the most obvious hallmark of leaf senescence. Phyllobilins, linear tetrapyrroles that are derived from opening of the chlorin macrocycle by the Rieske-type oxygenase PHEOPHORBIDE a OXYGENASE (PAO), are the end products of chlorophyll degradation. Phyllobilins carry defined modifications at several peripheral positions within the tetrapyrrole backbone. While most of these modifications are species-specific, hydroxylation at the C32 position is commonly found in all species analyzed to date. We demonstrate that this hydroxylation occurs in senescent chloroplasts of Arabidopsis thaliana. Using bell pepper (Capsicum annuum) chromoplasts, we establish that phyllobilin hydroxylation is catalyzed by a membrane-bound, molecular oxygen-dependent, and ferredoxin-dependent activity. As these features resemble the requirements of PAO, we considered membrane-bound Rieske-type oxygenases as potential candidates. Analysis of mutants of the two Arabidopsis Rieske-type oxygenases (besides PAO) uncovered that phyllobilin hydroxylation depends on TRANSLOCON AT THE INNER CHLOROPLAST ENVELOPE55 (TIC55). Our work demonstrates a catalytic activity for TIC55, which in the past has been considered as a redox sensor of protein import into plastids. Given the wide evolutionary distribution of both PAO and TIC55, we consider that chlorophyll degradation likely coevolved with land plants. PMID- 27655841 TI - Field of Genes: Uncovering EGRINs (Environmental Gene Regulatory Influence Networks) in Rice That Function during High-Temperature and Drought Stress. PMID- 27655843 TI - Side effects are under-reported in peer reviewed journals. PMID- 27655842 TI - EGRINs (Environmental Gene Regulatory Influence Networks) in Rice That Function in the Response to Water Deficit, High Temperature, and Agricultural Environments. AB - Environmental gene regulatory influence networks (EGRINs) coordinate the timing and rate of gene expression in response to environmental signals. EGRINs encompass many layers of regulation, which culminate in changes in accumulated transcript levels. Here, we inferred EGRINs for the response of five tropical Asian rice (Oryza sativa) cultivars to high temperatures, water deficit, and agricultural field conditions by systematically integrating time-series transcriptome data, patterns of nucleosome-free chromatin, and the occurrence of known cis-regulatory elements. First, we identified 5447 putative target genes for 445 transcription factors (TFs) by connecting TFs with genes harboring known cis-regulatory motifs in nucleosome-free regions proximal to their transcriptional start sites. We then used network component analysis to estimate the regulatory activity for each TF based on the expression of its putative target genes. Finally, we inferred an EGRIN using the estimated transcription factor activity (TFA) as the regulator. The EGRINs include regulatory interactions between 4052 target genes regulated by 113 TFs. We resolved distinct regulatory roles for members of the heat shock factor family, including a putative regulatory connection between abiotic stress and the circadian clock. TFA estimation using network component analysis is an effective way of incorporating multiple genome-scale measurements into network inference. PMID- 27655844 TI - The Receptor for Advanced Glycation Endproducts Drives T Cell Survival and Inflammation in Type 1 Diabetes Mellitus. AB - The ways in which environmental factors participate in the progression of autoimmune diseases are not known. After initiation, it takes years before hyperglycemia develops in patients at risk for type 1 diabetes (T1D). The receptor for advanced glycation endproducts (RAGE) is a scavenger receptor of the Ig family that binds damage-associated molecular patterns and advanced glycated endproducts and can trigger cell activation. We previously found constitutive intracellular RAGE expression in lymphocytes from patients with T1D. In this article, we show that there is increased RAGE expression in T cells from at-risk euglycemic relatives who progress to T1D compared with healthy control subjects, and in the CD8+ T cells in the at-risk relatives who do versus those who do not progress to T1D. Detectable levels of the RAGE ligand high mobility group box 1 were present in serum from at-risk subjects and patients with T1D. Transcriptome analysis of RAGE+ versus RAGE- T cells from patients with T1D showed differences in signaling pathways associated with increased cell activation and survival. Additional markers for effector memory cells and inflammatory function were elevated in the RAGE+ CD8+ cells of T1D patients and at-risk relatives of patients before disease onset. These studies suggest that expression of RAGE in T cells of subjects progressing to disease predates dysglycemia. These findings imply that RAGE expression enhances the inflammatory function of T cells, and its increased levels observed in T1D patients may account for the chronic autoimmune response when damage-associated molecular patterns are released after cell injury and killing. PMID- 27655846 TI - IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity. AB - Accumulating evidence shows that IL-17 is critically involved in diverse autoimmune diseases. However, its effect on the induction and progression of the humoral immune response is not fully understood. Using a preclinical model of IL 17-mediated dry eye disease, we demonstrate that upon encountering both the BCR and a secondary T cell signal, IL-17 can enhance B cell proliferation and germinal center formation in dry eye disease mice, suggesting that a stable Ag dependent T-B cell interaction is required. Additionally, IL-17 also promotes the differentiation of B cells into isotype-switched B cells and plasma cells. Furthermore, we show that Th17 cells are more effective than Th1 cells to provide B cell help. Reduced B cell response correlates with significant reduction in clinical disease after in vivo IL-17A neutralization. In conclusion, our findings demonstrate a new role of IL-17 in promoting autoimmunity in part through directly enhancing B cell proliferation, differentiation, and plasma cell generation. PMID- 27655847 TI - Boosting translational research in the U.K. AB - Investment in national infrastructure is critical for growth in early-phase translational research and experimental medicine. PMID- 27655845 TI - Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. AB - T cell activation in response to Ag is largely regulated by protein posttranslational modifications. Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O GlcNAc, IL-2 production and proliferation were compromised. T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. PMID- 27655848 TI - Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and safe and effective therapies are needed. Bile acids (BAs) and their receptors [including the nuclear receptor for BAs, farnesoid X receptor (FXR)] play integral roles in regulating whole-body metabolism and hepatic lipid homeostasis. We hypothesized that interruption of the enterohepatic BA circulation using a luminally restricted apical sodium-dependent BA transporter (ASBT) inhibitor (ASBTi; SC-435) would modify signaling in the gut liver axis and reduce steatohepatitis in high-fat diet (HFD)-fed mice. Administration of this ASBTi increased fecal BA excretion and messenger RNA (mRNA) expression of BA synthesis genes in liver and reduced mRNA expression of ileal BA-responsive genes, including the negative feedback regulator of BA synthesis, fibroblast growth factor 15. ASBT inhibition resulted in a marked shift in hepatic BA composition, with a reduction in hydrophilic, FXR antagonistic species and an increase in FXR agonistic BAs. ASBT inhibition restored glucose tolerance, reduced hepatic triglyceride and total cholesterol concentrations, and improved NAFLD activity score in HFD-fed mice. These changes were associated with reduced hepatic expression of lipid synthesis genes (including liver X receptor target genes) and normalized expression of the central lipogenic transcription factor, Srebp1c Accumulation of hepatic lipids and SREBP1 protein were markedly reduced in HFD-fed Asbt(-/-) mice, providing genetic evidence for a protective role mediated by interruption of the enterohepatic BA circulation. Together, these studies suggest that blocking ASBT function with a luminally restricted inhibitor can improve both hepatic and whole body aspects of NAFLD. PMID- 27655849 TI - Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. AB - Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-gamma production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML. PMID- 27655851 TI - The Sodium Paradox: Dysnatremia and Mortality in Patients Implanted With Extracorporeal Mechanical Circulatory Support Devices. AB - INTRODUCTION: Dysnatremia, abnormal serum sodium levels, has long been used as a marker for disease progression in heart failure patients. Classically, hyponatremia is associated with increased fluid volume in heart failure and is often a result of neuroendocrine dysfunction and poor cardiac output. Recent studies have noted that dysnatremia and hypernatremia are predictive of worsened outcomes in critical care and renal disease populations. We investigated the relationship between dysnatremia and postoperative outcomes in patients implanted with extracorporeal mechanical circulatory devices. METHODS: A total of 97 patients who underwent implantation with the CentriMag mechanical circulatory assist system were included in this retrospective study. Patients were divided into 2 groups based on preoperative serum sodium level cutoff of 135 mEq/L. Outcomes and mortality were compared between groups. RESULTS: The mean age for the study population was 56.21 +/- 15.13 years, and 57 patients (58.8%) were male. The mean time on CentriMag support was 22.7 days. Patients with serum sodium levels <=135 mEq/L were noted to have significantly worsened indicators of preoperative cardiac function. However, patients with serum sodium levels >135 mEq/L had significantly shorter postoperative survival ( P = .006). When entered into a multivariate Cox proportional hazards model, sodium was an independent predictor for increased risk of mortality (hazard ratio: 1.224; 95% confidence interval: 1.009-1.485; P = .040). CONCLUSION: Our results indicate that elevated preoperative sodium in patients undergoing implantation of a temporary mechanical circulatory support system is predictive of worsened postoperative survival. PMID- 27655852 TI - Factors Associated With the Increasing Rates of Discharges Directly Home From Intensive Care Units-A Direct From ICU Sent Home Study. AB - OBJECTIVES: To evaluate the relationship between rates of discharge directly to home (DDH) from the intensive care unit (ICU) and bed availability (ward and ICU). Also to identify patient characteristics that make them candidates for safe DDH and describe transfer delay impact on length of stay (LOS). METHODS: Retrospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between April 2003 and March 2015. RESULTS: Median age was 49 years (interquartile range [IQR]: 33.5-60.4), and the majority of the patients were males (54.8%). Median number of preexisting comorbidities was 5 (IQR: 2-7) diagnoses. Discharge directly to home increased from 28 (3.1% of all survivors) patients in 2003 to 120 (12.5%) patients in 2014. The mean annual rate of DDH was between 11% and 12% over the last 6 years. Approximately 62% (n = 397) of patients waited longer than 4 hours for a ward bed, with a median delay of 2.0 days (IQR: 0.5-4.7) before being DDH. There was an inverse correlation between ICU occupancy and DDH rates ( rP = -.55, P < .0001, 95% confidence interval [CI] = -0.36 to -0.69, R2 = .29). There was no correlation with ward occupancy and DDH rates ( rs = -.055, P = .64, 95% CI = -0.25 to 0.21). CONCLUSIONS: The DDH rates have been increasing over time at our institution and were inversely correlated with ICU bed occupancy but were not associated with ward occupancy. The DDH patients are young, have few comorbidities on admission, and few discharge diagnoses, which are usually reversible single system problems with low disease burden. Transfers to the ward are delayed in a majority of cases, leading to increased ICU LOS and likely increased overall hospital LOS as well. PMID- 27655853 TI - Comment on: Resistance gene naming and numbering: is it a new gene or not? PMID- 27655850 TI - IVIG-mediated protection against necrotizing pneumonia caused by MRSA. AB - New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of alpha-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus. PMID- 27655854 TI - Patient and public understanding and knowledge of antimicrobial resistance and stewardship in a UK hospital: should public campaigns change focus? AB - BACKGROUND: The rising global tide of antimicrobial resistance is a well described phenomenon. Employing effective and innovative antimicrobial stewardship strategies is an essential approach to combat this public health threat. Education of the public and patients is paramount to enable the success of such strategies. METHODS: A panel of hospital multidisciplinary healthcare professionals was set up and a short quiz containing true/false statements around antimicrobial stewardship and resistance was designed and piloted. An educational leaflet with the correct replies and supporting information was also produced and disseminated. Participants were recruited on a single day (18 November 2015) from the hospital outpatient clinics and the hospital outpatient pharmacy waiting room. RESULTS: One hundred and forty-five completed quizzes were returned, providing a total of 1450 answers. Overall, 934 of 1450 (64%) statements were scored correctly whilst 481 (33%) were scored incorrectly; 35 (3%) statements were left unscored. We speculate that these results may demonstrate that respondents understood the statements, as only a small proportion of statements were left unanswered. The question dealing with the definition of antimicrobial resistance and the question dealing with the definition of antimicrobial stewardship obtained the most incorrect replies (85% and 72%, respectively). However, a specific factual recall question regarding only one microorganism (MRSA) received the most correct responses (99%). CONCLUSIONS: We describe a simple, innovative method of engagement with patients and the general public to help educate and disseminate important public health messages around antimicrobial resistance and stewardship. We also identified the need for public health campaigns to address the knowledge gaps found around this topic. PMID- 27655855 TI - Risk factors for resistance to ciprofloxacin in community-acquired urinary tract infections due to Escherichia coli in an elderly population. AB - BACKGROUND: Antimicrobial resistance to ciprofloxacin is rising worldwide, especially in bacteria causing urinary tract infections (UTIs). Prudent use of current antibiotic drugs is therefore necessary. OBJECTIVES: We analysed (modifiable) risk factors for ciprofloxacin-resistant Escherichia coli. METHODS: Urinary cultures of UTIs caused by E. coli were collected from participants in the Rotterdam Study, a prospective cohort study in an elderly population, and analysed for susceptibility to ciprofloxacin. Multivariate logistic regression was performed to investigate several possible risk factors for resistance. RESULTS: Ciprofloxacin resistance in 1080 E. coli isolates was 10.2%. Multivariate analysis showed that higher age (OR 1.03; 95% CI 1.00-1.05) and use of two (OR 5.89; 95% CI 3.45-10.03) and three or more (OR 3.38; 95% CI 1.92-5.97) prescriptions of fluoroquinolones were associated with ciprofloxacin resistance, while no association between fluoroquinolone use more than 1 year before culture and ciprofloxacin resistance could be demonstrated. Furthermore, a high intake of pork (OR 3.68; 95% CI 1.36-9.99) and chicken (OR 2.72; 95% CI 1.08-6.85) and concomitant prescription of calcium supplements (OR 2.51; 95% CI 1.20-5.22) and proton pump inhibitors (OR 2.04; 95% CI 1.18-3.51) were associated with ciprofloxacin resistance. CONCLUSIONS: Ciprofloxacin resistance in community acquired UTI was associated with a high intake of pork and chicken and with concomitant prescription of calcium supplements and proton pump inhibitors. Modification of antibiotic use in animals as well as temporarily stopping the prescription of concomitant calcium and proton pump inhibitors need further evaluation as strategies to prevent ciprofloxacin resistance. PMID- 27655856 TI - Long-term clonal dynamics of Enterococcus faecium strains causing bloodstream infections (1995-2015) in Spain. AB - OBJECTIVES: To investigate the population structure of Enterococcus faecium causing bloodstream infections (BSIs) in a tertiary Spanish hospital with low glycopeptide resistance, and to enhance our knowledge of the dynamics of emergence and spread of high-risk clonal complexes. METHODS: All available E. faecium causing BSIs (n = 413) in our hospital (January 1995-May 2015) were analysed for antibiotic susceptibility (CLSI), putative virulence traits (PCR, esp, hylEfm) and clonal relationship (SmaI-PFGE, MLST evaluated by goeBURST and BAPS). RESULTS: The increased incidence of BSIs caused by enterococci [2.30/00 of attended patients (inpatients and outpatients) in 1996 to 3.00/00 in 2014] significantly correlated with the increase in BSIs caused by E. faecium (0.330/00 of attended patients in 1996 to 1.30/00 in 2014). The BSIs Enterococcus faecalis:E. faecium ratio changed from 5:1 in 1996 to 1:1 in 2014. During the last decade an increase in E. faecium BSIs episodes in cancer patients (10.9% in 1995-2005 and 37.1% in 2006-15) was detected. Ampicillin-susceptible E. faecium (ASEfm; different STs/BAPS) and ampicillin-resistant E. faecium (AREfm; ST18/ST17 BAPS 3.3a) isolates were recovered throughout the study. Successive waves of BAPS 2.1a-AREfm (ST117, ST203 and ST80) partially replaced ASEfm and ST18-AREfm since 2006. CONCLUSIONS: Different AREfm clones (belonging to BAPS 2.1a and BAPS 3.3a) consistently isolated during the last decade from BSIs might be explained by a continuous and dense colonization (favouring both invasion and cross transmission) of hospitalized patients. High-density colonization by these clones is probably enhanced in elderly patients by heavy and prolonged antibiotic exposure, particularly in oncological patients. PMID- 27655857 TI - Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients. AB - BACKGROUND: Pharmacokinetics (PK) and pharmacodynamics of efavirenz and its 8 hydroxy metabolite (8-OH-efavirenz) have not been robustly evaluated in older HIV infected persons. OBJECTIVES: We investigated relationships between neuropsychological (NP) performance and efavirenz and 8-OH-efavirenz PK in HIV infected individuals >50 years of age. METHODS: A cross-sectional study of HIV infected adults on an efavirenz-containing regimen. The 12 and 18 h post-dose plasma efavirenz and 8-OH-efavirenz were quantified. CYP2B6 polymorphisms were investigated. Participants underwent neuropsychological tests; surveys were used for depression, sleep quality and anxiety. We investigated potential correlations of efavirenz and 8-OH-efavirenz plasma concentrations with NP performance, sleep, depression, anxiety and CYP2B6 polymorphisms. RESULTS: Thirty participants (24 men and 6 women) with mean age 57 years (range 50-68). Plasma efavirenz concentrations did not correlate with NP performance; however, higher plasma 8-OH efavirenz correlated with better learning (P = 0.002), language (P = 0.002) and total NP z-scores (P = 0.003). No correlation was seen for efavirenz or 8-OH efavirenz with sleep, anxiety or depression. Median 12 and 18 h efavirenz plasma concentrations were 1967 ng/mL (IQR 1476-2394) and 1676 ng/mL (IQR 1120-2062), respectively. Median 12 and 18 h 8-OH-efavirenz plasma concentrations were 378 ng/mL (IQR 223-589) and 384 ng/mL (IQR 216-621), respectively. CYP2B6 G516T was associated with significantly higher plasma efavirenz at 12 and 18 h (P = 0.02) but not worse NP function. CONCLUSIONS: Better neurocognitive functioning was associated with higher 8-OH-efavirenz but not efavirenz plasma concentrations. No correlation was observed with sleep or depression. These findings point to a need for greater understanding of the metabolic profile of efavirenz and 8-OH efavirenz in plasma and the CNS and relationships with antiviral effect and neurotoxicity. PMID- 27655858 TI - Less-drug regimen including atazanavir in maintenance treatment of HIV infection: how, who, when, why? AB - For many patients living with HIV-1, the efficacy of combined ART (cART) has made the infection turn to a chronic disease. Because cART is associated with a risk of long-term toxicity, switching patients with virological success to another therapy remains a major issue. Studies undertaken and published over recent years have shown that switching patients exhibiting virological suppression to less drug regimens (LDR) is a possible option of maintenance strategy. The use of ritonavir-boosted PIs (PI/r) as the backbone of LDR-based maintenance therapy is consistent with their virological potency and a high genetic barrier of resistance. Atazanavir is the most documented PI/r regarding maintenance in dual therapy, with favourable results in terms of virological suppression, tolerance improvement and absence of emergence of mutations. Furthermore, atazanavir is the only commonly prescribed PI that can be used after withdrawal of ritonavir, with maintenance of virological suppression whatever the backbone of associated NRTIs. Based on clinical studies, and taking into account the characteristics of the patients included, one may consider that for any patient with a virological suppression on cART for at least 12 months, with the nadir CD4 >100 cells/mm3 and an absence of encephalitis, an LDR-based maintenance therapy including atazanavir can be considered. Cumulative genotypes must be available to make sure that the LDR will not jeopardize future therapeutic options. The final decision regarding the most appropriate LDR must be guided by the objectives shared by the physician and his/her patient. PMID- 27655860 TI - Beyond Bedlam. PMID- 27655859 TI - Different impact of raltegravir versus efavirenz on CD4/CD8 ratio recovery in HIV infected patients. AB - OBJECTIVES: A low CD4/CD8 ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 ratio. METHODS: We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duration of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS: A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS: We herein show that normalization of the CD4/CD8 ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored. PMID- 27655862 TI - Increasing physicians in hospital staff does not improve quality of care, US study suggests. PMID- 27655863 TI - Government must spell out how mental health will achieve parity with physical health, say MPs. PMID- 27655861 TI - Predicting inpatient clinical order patterns with probabilistic topic models vs conventional order sets. AB - Objective: Build probabilistic topic model representations of hospital admissions processes and compare the ability of such models to predict clinical order patterns as compared to preconstructed order sets. Materials and Methods: The authors evaluated the first 24 hours of structured electronic health record data for > 10 K inpatients. Drawing an analogy between structured items (e.g., clinical orders) to words in a text document, the authors performed latent Dirichlet allocation probabilistic topic modeling. These topic models use initial clinical information to predict clinical orders for a separate validation set of > 4 K patients. The authors evaluated these topic model-based predictions vs existing human-authored order sets by area under the receiver operating characteristic curve, precision, and recall for subsequent clinical orders. Results: Existing order sets predict clinical orders used within 24 hours with area under the receiver operating characteristic curve 0.81, precision 16%, and recall 35%. This can be improved to 0.90, 24%, and 47% ( P < 10 -20 ) by using probabilistic topic models to summarize clinical data into up to 32 topics. Many of these latent topics yield natural clinical interpretations (e.g., "critical care," "pneumonia," "neurologic evaluation"). Discussion: Existing order sets tend to provide nonspecific, process-oriented aid, with usability limitations impairing more precise, patient-focused support. Algorithmic summarization has the potential to breach this usability barrier by automatically inferring patient context, but with potential tradeoffs in interpretability. Conclusion: Probabilistic topic modeling provides an automated approach to detect thematic trends in patient care and generate decision support content. A potential use case finds related clinical orders for decision support. PMID- 27655865 TI - Women Veterans' Experiences of Intimate Partner Violence and Non-Partner Sexual Assault in the Context of Military Service: Implications for Supporting Women's Health and Well-Being. AB - Women who have served in the military in the United States experience high rates of intimate partner violence (IPV) and non-partner sexual assault (SA). The military setting presents challenges and opportunities not experienced in other employment contexts that may compound the negative impacts of IPV/SA on women's lives. The purpose of this study was to explore the intersection of women's experiences of IPV/SA and military service through analysis of women veterans' narrative accounts. We conducted in-depth face-to-face qualitative interviews with 25 women veterans receiving primary care at a U.S. Veterans Affairs Medical Center. We draw upon Adler and Castro's (2013) Military Occupational Mental Health Model to frame our understanding of the impact of IPV/SA as a stressor in the military cultural context and to inform efforts to prevent, and support women service members who have experienced, these forms of violence. Our findings highlight the impact of IPV/SA on women's military careers, including options for entering and leaving military service, job performance, and opportunities for advancement. Women's narratives also reveal ways in which the military context constrains their options for responding to and coping with experiences of IPV/SA. These findings have implications for prevention of, and response to, intimate partner or sexual violence experienced by women serving in the military and underscore the need for both military and civilian communities to recognize and address the negative impact of such violence on women service members before, during, and after military service. PMID- 27655864 TI - Three-dimensional echocardiography in congenital heart disease: an expert consensus document from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. AB - Three-dimensional echocardiography (3DE) has become important in the management of patients with congenital heart disease (CHD), particularly with pre-surgical planning, guidance of catheter intervention, and functional assessment of the heart. 3DE is increasingly used in children because of good acoustic windows and the non-invasive nature of the technique. The aim of this paper is to provide a review of the optimal application of 3DE in CHD including technical considerations, image orientation, application to different lesions, procedural guidance, and functional assessment. PMID- 27655866 TI - Prevalence and Predictors of Bidirectional Violence in Survivors of Intimate Partner Violence Residing at Shelters. AB - There has been a long-standing debate regarding whether or not there is gender symmetry in intimate partner violence (IPV); however, shelter samples have been understudied thus far. This study investigates the prevalence and predictors of IPV perpetration in a sample of 227 women in battered women's shelters. Participants were asked to complete a number of measures assessing demographics, Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV TR) diagnoses, traumatic life events, and perpetration and victimization of IPV. Although the vast majority of women in this sample (93%) report perpetrating some form of IPV, few women endorsed violence that was not mutual (5.3%). Furthermore, for every type of IPV assessed, women were victimized significantly more than they perpetrated. Results also indicate that women's perpetration of IPV, and predictors of such perpetration, varied across type, severity, and measurement of violence. However, most IPV outcome variables were predicted by women's experience of victimization. Taken as a whole, these results support the assertion that context matters when examining the relative rates of perpetration as well as its predictors. PMID- 27655867 TI - It All Just Piles Up: Challenges to Victim Credibility Accumulate to Influence Sexual Assault Case Processing. AB - The underreporting of sexual assault is well known to researchers, practitioners, and victims. When victims do report, their complaints are unlikely to end in arrest or prosecution. Existing research on police discretion suggests that the police decision to arrest for sexual assault offenses can be influenced by a variety of legal and extra-legal factors particularly challenges to victim credibility. Although extant literature examines the effects of individual behaviors on police outcomes, less is known about how the accumulation of these behaviors, attributions, and characteristics affects police decision making. Using data collected from the Los Angeles Police Department and Sheriff's Department, we examine one police decision point-the arrest to fill this gap in the literature. First, we examine the extent to which the effects of potential challenges to victim credibility, based on victim characteristics and behaviors, influence the arrest decision, and next, how these predictors vary across circumstances. Specifically, we examine how factors that challenge victim credibility affect the likelihood of arrest in sexual assault cases where the victim and offender are strangers, acquaintances, and intimate partners. PMID- 27655868 TI - A Virus-Like Particle Vaccine Elicits Broad Neutralizing Antibody Responses in Humans to All Chikungunya Virus Genotypes. AB - Chikungunya virus (CHIKV) is an alphavirus that has emerged as a global health burden. There are 3 CHIKV genotypes: Asian, West African, and Eastern/Central/South African. No licensed CHIKV vaccine is available, and whether the antibody response elicited by one genotype can neutralize heterologous genotypes is unclear. We assessed neutralizing antibody (NAb) responses of volunteers in a phase 1 study of a CHIKV vaccine against 9 viral strains representing all 3 genotypes. Minimal differences in vaccine-elicited NAb responses were observed among genotypes, suggesting that vaccination with a single CHIKV strain can elicit cross-protective NAbs against all 3 genotypes. PMID- 27655869 TI - Clinical Predictors of Critical Lower Respiratory Tract Illness Due to Respiratory Syncytial Virus in Infants and Children: Data to Inform Case Definitions for Efficacy Trials. AB - We analyzed data from 524 Argentinean infants hospitalized with lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) to inform selection of clinical end points for RSV vaccine efficacy trials. Cases of LRTI due to RSV that required a mask, continuous or bilevel positive airway pressure, or mechanical ventilation were classified as critical. Oxygen saturation of <=90%, tachypnea, and tachycardia were each associated with an increased odds of critical LRTI due to RSV (adjusted odds ratios [ORs], 2.30 [95% confidence interval {CI}, 1.26-4.24; P = .007], 2.22 [95% CI, 1.19-4.16; P = .012], and 2.35 [95% CI, 1.22-4.50; P = .010], respectively). The odds of critical LRTI due to RSV increased substantially (OR, 8.57; 95% CI, 2.19-73.5; P = .001) among individuals with >=2 indicators. Lower chest wall indrawing was not associated with critical disease. PMID- 27655871 TI - Timothy Evans: Keen to cut variations in practice. PMID- 27655870 TI - Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy. AB - Pregnancy-induced alterations in immunity may contribute to the increased morbidity associated with influenza A virus infection during pregnancy. We characterized the immune response of monocytes and plasmacytoid dendritic cells (pDCs) to influenza A virus infection in 21 pregnant and 21 nonpregnant women. In pregnant women, monocytes and pDCs exhibit an exaggerated proinflammatory immune response to 2 strains of influenza A virus, compared with nonpregnant women, characterized by increased expression of major histocompatibility complex class II (approximately 2.0-fold), CD69 (approximately 2.2-fold), interferon gamma induced protein 10 (approximately 2.0-fold), and macrophage inflammatory protein 1beta (approximately 1.5-fold). This enhanced innate inflammatory response during pregnancy could contribute to pulmonary inflammation following influenza A virus infection. PMID- 27655873 TI - Use of aspirin as sole oral antiplatelet therapy in acute flow diversion for ruptured dissecting aneurysms. AB - Subarachnoid hemorrhage secondary to rupture of a circumferential dissecting aneurysm continues to be a treatment dilemma. Vessel sacrifice, when possible, continues to be the safest option but in certain cases this is not possible due to lack of collateral supply. In such cases, coil assisted endovascular flow diversion has become a potential option but the requirement for dual antiplatelet therapy in an unsecured intracranial aneurysm continues to raise concern.We present a 48-year-old man with a World Federation of Neurological Surgeons grade 5 subarachnoid hemorrhage, secondary to a ruptured intradural left vertebral artery dissecting aneurysm, who was treated successfully with a pipeline embolization device with Shield technology using aspirin and a single intravenous loading dose of abciximab. To our knowledge, this is the first case of an acute flow diversion performed using only aspirin as the sole oral antiplatelet agent. PMID- 27655875 TI - Acute optic neuritis with diffusion restriction on MRI. PMID- 27655874 TI - Acute osteoarthritis: exuberant presentation of an unusual condition in the neonatal period. PMID- 27655876 TI - Gonadotropin-releasing hormone agonist against severe aggression in autism. AB - Aggression in patients with autism spectrum disorder (ASD) presents an important therapeutic challenge. Conventional treatment appears to be inadequate in a number of cases. The occurrence of severe aggressive symptoms since the inception of adolescence in a male patient with ASD suggested a hormonal influence by androgens. Conventional treatment with antipsychotic and antiepileptic drugs and benzodiazepines was ineffective. A subcutaneous long-acting gonadotropin releasing hormone agonist (GnRH agonist) injection was given on a monthly basis resulting in a substantial improvement in his aggressive behaviour and renewed socialisation. PMID- 27655872 TI - A Golgi rhomboid protease Rbd2 recruits Cdc48 to cleave yeast SREBP. AB - Hypoxic growth of fungi requires sterol regulatory element-binding protein (SREBP) transcription factors, and human opportunistic fungal pathogens require SREBP activation for virulence. Proteolytic release of fission yeast SREBPs from the membrane in response to low oxygen requires the Golgi membrane-anchored Dsc E3 ligase complex. Using genetic interaction arrays, we identified Rbd2 as a rhomboid family protease required for SREBP proteolytic processing. Rbd2 is an active, Golgi-localized protease that cleaves the transmembrane segment of the TatA rhomboid model substrate. Epistasis analysis revealed that the Dsc E3 ligase acts on SREBP prior to cleavage by Rbd2. Using APEX2 proximity biotinylation, we demonstrated that Rbd2 binds the AAA-ATPase Cdc48 through a C-terminal SHP box. Interestingly, SREBP cleavage required Rbd2 binding of Cdc48, consistent with Cdc48 acting to recruit ubiquitinylated substrates. In support of this claim, overexpressing a Cdc48-binding mutant of Rbd2 bypassed the Cdc48 requirement for SREBP cleavage, demonstrating that Cdc48 likely plays a role in SREBP recognition. In the absence of functional Rbd2, SREBP precursor is degraded by the proteasome, indicating that Rbd2 activity controls the balance between SREBP activation and degradation. PMID- 27655877 TI - Irreversible electroporation in the curative treatment of Ewing's sarcoma. AB - Ewing's sarcoma (ES) is the second most common paediatric cancer of the bone. Standard therapy includes surgery or radiation for local control of primary and relapsed lesions and chemotherapy for systemic control. Irreversible electroporation (IRE), which uses short electrical pulses to induce pores and ablate neoplastic cells, has emerged as an alternative method of local control for inoperable metastatic liver and lung lesions. We present the first case in which IRE was used for local control of bony ES. This method has achieved successful local tumour control in our patient for 3 years. PMID- 27655878 TI - Primary tuberculous osteomyelitis of the mandible in a 3-year-old child. AB - A 3-year-old girl child presented with swelling in her right lower jaw that had started 5 days previously. History revealed the child being non-immunised. Initial-evaluation revealed proptosis and bony hard swelling over the right body of the mandible. Radiological evaluation including a CT scan indicated expansile osteolytic lesion involving the body-ramus with onion-peel periosteal reaction suggesting osteomyelitis/malignancy. Blood investigations showed raised erythrocyte sedimentation rate and eosinophilia. Family screening for tuberculosis (TB) revealed that the patient, her father and siblings were PPD positive though chest screening and sputum examinations were negative in all of them. Lesion biopsy showed acute/chronic osteomyelitis with eosinophilia, tilting diagnosis towards eosinophilic granuloma/Hand-Schuller-Christian disease. Further investigations for diabetes insipidus, histiocytosis-X, skull-pelvic-femur radiographs, abdominal ultrasonography, ophthalmic consultation and PCR-TB test were negative. Histology, radiography, purified protein derivative (PPD)-positive result and history led to the diagnosis of primary TB of the mandible. Complete resolution occurred following antitubercular therapy. The case report emphasises that diagnosis of TB can sometimes be based on circumstantial evidence and positive response to antitubercular therapy even in view of a negative PCR result. PMID- 27655879 TI - Unusual cause of paraparesis in a patient with Cushing's syndrome. AB - Paraparesis is a rare manifestation in patients with Cushing's syndrome and the causes include vertebral compression fracture, hypokalaemia, spinal epidural lipomatosis, paraneoplastic syndrome and metastasis to the vertebrae and spinal cord. We report an unusual cause of paraparesis due to radiation-induced myelomalacia in a patient with adrenocortical carcinoma-associated Cushing's syndrome, who are predisposed to radiation-induced injury. PMID- 27655880 TI - Spontaneous evisceration of the appendix through an incisional hernia at rest. PMID- 27655881 TI - A bilateral macular star and optic disc oedema. PMID- 27655882 TI - Capillary and Venous Lactate Agreement: a pilot prospective observational study. AB - BACKGROUND: Blood lactate is a marker of patient illness severity. Capillary lactate (CAP-LACT) measurement can potentially improve patient screening; however, it has poor evidence of clinical utility. AIM: We aimed to investigate agreement between CAP-LACT and peripheral venous lactate (PV-LACT). METHODS: We performed a prospective observational pilot study of 99 patients requiring lactate measurement. Paired CAP-LACT and PV-LACT was recorded. Agreement was determined by Bland-Altman analysis. RESULTS: Bias was 0.2 mmol/L, with 95% limits of agreement from -1.9 to 2.3. CONCLUSIONS: CAP-LACT has poor agreement with PV-LACT. Further research is needed to improve its potential clinical utility. PMID- 27655883 TI - Performance of a simplified termination of resuscitation rule for adult traumatic cardiopulmonary arrest in the prehospital setting. AB - OBJECTIVE: The prehospital termination of resuscitation (TOR) guidelines for traumatic cardiopulmonary arrest (TCPA) was proposed in 2003. Its multiple descriptors of cases where efforts can be terminated make it complex to apply in the field. Here we proposed a simplified rule and evaluated its predictive performance. METHODS: We analysed Utstein registry data for 2009-2013 from a Taipei emergency medical service to test a simplified TOR rule that comprises two criteria: blunt trauma injury and the presence of asystole. Enrolees were adults (>=18 years) with TCPA. The predicted outcome was in-hospital death. We compared the areas under the curve (AUC) of the simple rule with each of four descriptors in the guidelines and with a combination of all four to assess their discriminatory ability. Test characteristics were calculated to assess predictive performance. RESULTS: A total of 893 TCPA cases were included. Blunt trauma occurred in 459 (51.4%) cases and asystole in 384 (43.0%). In-hospital mortality was 854 (95.6%) cases. The simplified TOR rule had greater discriminatory ability (AUC 0.683, 95% CI 0.618 to 0.747) compared with any single descriptor in the 2003 guidelines (range of AUC: 0.506-0.616) although the AUC was similar when all four were combined (AUC 0.695, 95% CI 0.615 to 0.775). The specificity of the simplified rule was 100% (95% CI 88.8% to 100%) and positive predictive value 100% (95% CI 96.8% to 100%). The false positive value, false negative value and decreased rate of unnecessary transport were 0% (95% CI 0% to 3.2%), 94.8% (95% CI 92.9% to 96.2%) and 16.4% (95% CI 14.1% to 19.1%), respectively. CONCLUSIONS: The simplified TOR rule appears to accurately predict non-survivors in adults with TCPA in the prehospital setting. PMID- 27655884 TI - Clinical assessment and management of multimorbidity: summary of NICE guidance. PMID- 27655885 TI - Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine. AB - Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID- 27655886 TI - Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development. AB - Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals. PMID- 27655887 TI - Strain analysis of protein structures and low dimensionality of mechanical allosteric couplings. AB - In many proteins, especially allosteric proteins that communicate regulatory states from allosteric to active sites, structural deformations are functionally important. To understand these deformations, dynamical experiments are ideal but challenging. Using static structural information, although more limited than dynamical analysis, is much more accessible. Underused for protein analysis, strain is the natural quantity for studying local deformations. We calculate strain tensor fields for proteins deformed by ligands or thermal fluctuations using crystal and NMR structure ensembles. Strains-primarily shears-show deformations around binding sites. These deformations can be induced solely by ligand binding at distant allosteric sites. Shears reveal quasi-2D paths of mechanical coupling between allosteric and active sites that may constitute a widespread mechanism of allostery. We argue that strain-particularly shear-is the most appropriate quantity for analysis of local protein deformations. This analysis can reveal mechanical and biological properties of many proteins. PMID- 27655888 TI - Integrating biogeochemistry with multiomic sequence information in a model oxygen minimum zone. AB - Microorganisms are the most abundant lifeform on Earth, mediating global fluxes of matter and energy. Over the past decade, high-throughput molecular techniques generating multiomic sequence information (DNA, mRNA, and protein) have transformed our perception of this microcosmos, conceptually linking microorganisms at the individual, population, and community levels to a wide range of ecosystem functions and services. Here, we develop a biogeochemical model that describes metabolic coupling along the redox gradient in Saanich Inlet a seasonally anoxic fjord with biogeochemistry analogous to oxygen minimum zones (OMZs). The model reproduces measured biogeochemical process rates as well as DNA, mRNA, and protein concentration profiles across the redox gradient. Simulations make predictions about the role of ubiquitous OMZ microorganisms in mediating carbon, nitrogen, and sulfur cycling. For example, nitrite "leakage" during incomplete sulfide-driven denitrification by SUP05 Gammaproteobacteria is predicted to support inorganic carbon fixation and intense nitrogen loss via anaerobic ammonium oxidation. This coupling creates a metabolic niche for nitrous oxide reduction that completes denitrification by currently unidentified community members. These results quantitatively improve previous conceptual models describing microbial metabolic networks in OMZs. Beyond OMZ-specific predictions, model results indicate that geochemical fluxes are robust indicators of microbial community structure and reciprocally, that gene abundances and geochemical conditions largely determine gene expression patterns. The integration of real observational data, including geochemical profiles and process rate measurements as well as metagenomic, metatranscriptomic and metaproteomic sequence data, into a biogeochemical model, as shown here, enables holistic insight into the microbial metabolic network driving nutrient and energy flow at ecosystem scales. PMID- 27655889 TI - Lateral association and elongation of vimentin intermediate filament proteins: A time-resolved light-scattering study. AB - Vimentin intermediate filaments (IFs) are part of a family of proteins that constitute one of the three filament systems in the cytoskeleton, a major contributor to cell mechanics. One property that distinguishes IFs from the other cytoskeletal filament types, actin filaments and microtubules, is their highly hierarchical assembly pathway, where a lateral association step is followed by elongation. Here we present an innovative technique to follow the elongation reaction in solution and in situ by time-resolved static and dynamic light scattering, thereby precisely capturing the relevant time and length scales of seconds to minutes and 60-600 nm, respectively. We apply a quantitative model to our data and succeed in consistently describing the entire set of data, including particle mass, radius of gyration, and hydrodynamic radius during longitudinal association. PMID- 27655890 TI - Detection of deep stratospheric intrusions by cosmogenic 35S. AB - The extent to which stratospheric intrusions on synoptic scales influence the tropospheric ozone (O3) levels remains poorly understood, because quantitative detection of stratospheric air has been challenging. Cosmogenic 35S mainly produced in the stratosphere has the potential to identify stratospheric air masses at ground level, but this approach has not yet been unambiguously shown. Here, we report unusually high 35S concentrations (7,390 atoms m-3; ~16 times greater than annual average) in fine sulfate aerosols (aerodynamic diameter less than 0.95 um) collected at a coastal site in southern California on May 3, 2014, when ground-level O3 mixing ratios at air quality monitoring stations across southern California (43 of 85) exceeded the recently revised US National Ambient Air Quality Standard (daily maximum 8-h average: 70 parts per billion by volume). The stratospheric origin of the significantly enhanced 35S level is supported by in situ measurements of air pollutants and meteorological variables, satellite observations, meteorological analysis, and box model calculations. The deep stratospheric intrusion event was driven by the coupling between midlatitude cyclones and Santa Ana winds, and it was responsible for the regional O3 pollution episode. These results provide direct field-based evidence that 35S is an additional sensitive and unambiguous tracer in detecting stratospheric air in the boundary layer and offer the potential for resolving the stratospheric influences on the tropospheric O3 level. PMID- 27655891 TI - High pressure-induced distortion in face-centered cubic phase of thallium. AB - The complex and unusual high-pressure phase transition of III-A (i.e. Al, Ga, and In) metals have been investigated in the last several decades because of their interesting periodic table position between the elements having metallic and covalent bonding. Our present first principles-based electronic structure calculations and experimental investigation have revealed the unusual distortion in face-centered cubic (f.c.c.) phase of the heavy element thallium (Tl) induced by the high pressure. We have predicted body-centered tetragonal (b.c.t) phase at 83 GPa using an evolutionary algorithm coupled with ab initio calculations, and this prediction has been confirmed with a slightly distorted parameter ([Formula: see text] * a - c)/c lowered by 1% using an angle-dispersive X-ray diffraction technique. The density functional theory (DFT)-based calculations suggest that s p mixing states and the valence-core overlapping of 6s and 5d states play the most important roles for the phase transitions along the pathway h.c.p[Formula: see text]f.c.c.[Formula: see text]b.c.t. PMID- 27655892 TI - How curvature-generating proteins build scaffolds on membrane nanotubes. AB - Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube's length. Our work implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30-40% of a tube's surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes. PMID- 27655893 TI - Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants. AB - Brassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helix-loop-helix transcription factor CESTA (CES) can contribute to the constitutive expression of the C REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation. PMID- 27655894 TI - Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus. AB - A stressful event results in secretion of glucocorticoid hormones, which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus to regulate cognitive and affective responses to the challenge. MRs are already highly occupied by low glucocorticoid levels under baseline conditions, whereas GRs only become substantially occupied by stress- or circadian-driven glucocorticoid levels. Currently, however, the binding of MRs and GRs to glucocorticoid-responsive elements (GREs) within hippocampal glucocorticoid target genes under such physiological conditions in vivo is unknown. We found that forced swim (FS) stress evoked increased hippocampal RNA expression levels of the glucocorticoid-responsive genes FK506-binding protein 5 (Fkbp5), Period 1 (Per1), and serum- and glucocorticoid-inducible kinase 1 (Sgk1). Chromatin immunoprecipitation (ChIP) analysis showed that this stressor caused substantial gene-dependent increases in GR binding and surprisingly, also MR binding to GREs within these genes. Different acute challenges, including novelty, restraint, and FS stress, produced distinct glucocorticoid responses but resulted in largely similar MR and GR binding to GREs. Sequential and tandem ChIP analyses showed that, after FS stress, MRs and GRs bind concomitantly to the same GRE sites within Fkbp5 and Per1 but not Sgk1 Thus, after stress, MRs and GRs seem to bind to GREs as homo- and/or heterodimers in a gene-dependent manner. MR binding to GREs at baseline seems to be restricted, whereas after stress, GR binding may facilitate cobinding of MR. This study reveals that the interaction of MRs and GRs with GREs within the genome constitutes an additional level of complexity in hippocampal glucocorticoid action beyond expectancies based on ligand-receptor interactions. PMID- 27655896 TI - US Air Force Behavioral Health Optimization Program: team members' satisfaction and barriers to care. AB - BACKGROUND: Research has shown significant contribution of integrated behavioural health care; however, less is known about the perceptions of primary care providers towards behavioural health professionals. OBJECTIVE: The current study examined barriers to care and satisfaction with integrated behavioural health care from the perspective of primary care team members. DESIGN: This study utilized archival data from 42 treatment facilities as part of ongoing program evaluation of the Air Force Medical Service's Behavioral Health Optimization Program. SETTING: This study was conducted in a large managed health care organization for active duty military and their families, with specific clinic settings that varied considerably in regards to geographic location, population diversity and size of patient empanelment. STUDY PARTICIPANTS: De-identified archival data on 534 primary care team members were examined. RESULTS: Team members at larger facilities rated access and acuity concerns as greater barriers than those from smaller facilities (t(533) = 2.57, P < 0.05). Primary Care Managers (PCMs) not only identified more barriers to integrated care (beta = 0.07, P < 0.01) but also found services more helpful to the primary care team (t(362.52) = 1.97, P = 0.05). Barriers to care negatively impacted perceived helpfulness of integrated care services for patients (beta = -0.12, P < 0.01) and team members, particularly among non-PCMs (beta = -0.11, P < 0.01). CONCLUSIONS: Findings highlight the potential benefits of targeted training that differs in facilities of larger empanelment and is mindful of team members' individual roles in a Patient Centered Medical Home. In particular, although generally few barriers were perceived, given the impact these barriers have on perception of care, efforts should be made to decrease perceived barriers to integrated behavioural health care among non-PCM team members. PMID- 27655897 TI - Who to handover: a case-control study of a novel scoring system to prioritise handover of internal medicine inpatients. AB - BACKGROUND: Handover of patients between care providers is a critical event in patient care. There is, however, little evidence to guide the handover process, including determining which patients to handover. AIM: Compare the ability of gestalt-based handover with two structured scores, the modified early warning score (MEWS) and our novel iHAND clinical decision support system, to predict which patients will be assessed by a physician overnight. METHODS: This case control study included 90 inpatients, comprising 32 patients assessed overnight (cases) and 58 patients not assessed overnight (controls) at a teaching hospital in British Columbia, Canada (May 2012). Gestalt, MEWS and iHAND scores were analysed against patients seen overnight using logistic regression and receiver operating characteristic (ROC) curves. RESULTS: Neither current gestalt-based handover practice (odds ratio (OR) 1.50, 95% CI 0.89 to 3.83) nor MEWS (OR 0.96, 95% CI 0.75 to 1.24, area under the ROC curve (AUC) 0.61, 95% CI 0.49 to 0.73) were significantly associated with need to be seen overnight. The iHAND score was associated with need to be seen (OR 1.93, 95% CI 1.24 to 3.02, AUC 0.70, 95% CI 0.60 to 0.81). CONCLUSIONS: The iHAND score had moderate ability to predict which patients required assessment overnight, while MEWS score and current gestalt approach correlated poorly, suggesting the iHAND score may help prioritisation of patients likely to be seen overnight for handover. PMID- 27655895 TI - Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. AB - Although multiagent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die because of chemorefractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape at relapse in pediatric ALL cases. These analyses identified numerous relapse-associated mutated genes intertwined in chemotherapy resistance-related protein complexes. In this context, RAS-MAPK pathway-activating mutations in the neuroblastoma RAS viral oncogene homolog (NRAS), kirsten rat sarcoma viral oncogene homolog (KRAS), and protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) genes were present in 24 of 55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, whereas in others RAS mutant clones present at diagnosis were replaced by RAS wild-type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Consistently, functional dissection of mouse and human wild-type and mutant RAS isogenic leukemia cells demonstrated induction of methotrexate resistance but also improved the response to vincristine in mutant RAS-expressing lymphoblasts. These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution in relapsed ALL, and demonstrate a previously unrecognized dual role of RAS mutations as drivers of both sensitivity and resistance to chemotherapy. PMID- 27655899 TI - A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis. AB - Brown adipose tissue (BAT) oxidizes fatty acids for thermogenesis and could therefore be considered as part of a new strategy in combating obesity and associated metabolic diseases. It is well established that aging is accompanied by a decline of brown adipocyte regenerative capacity. How aging contributes to this loss is poorly understood. Here, we identify a long noncoding RNA, uc.417, which is transcribed from an ultraconserved region in rodents. Expression of uc.417 increases with age. Ectopic expression of uc.417 impairs adipogenesis and the thermogenic program in brown adipocytes. However, uc.417 is not required for brown fat function. In vivo, uc.417 attenuates the cold-induced thermogenic program in mouse BAT. Moreover, we find that uc.417 moderately inhibits phosphorylation of p38MAPK without affecting the total protein level of p38MAPK. The p38MAPK pathway is essential for activating BAT to stimulate uncoupling protein 1 gene expression. The data point to uc.417 as being an important factor in an age-dependent loss of function of brown adipose tissue.-Cui, X., You, L., Li, Y., Zhu, L., Zhang, F., Xie, K., Cao, Y., Ji, C., Guo, X. A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis. PMID- 27655898 TI - Baby Boomers and Birth Certificates: Early-Life Socioeconomic Status and Cancer Risk in Adulthood. AB - BACKGROUND: Early-life socioeconomic status (SES) may play a role in cancer risk in adulthood. However, measuring SES retrospectively presents challenges. Parental occupation on the birth certificate is a novel method of ascertaining early-life SES that has not been applied in cancer epidemiology. METHODS: For a Baby-Boom cohort born from 1945-1959 in two Utah counties, individual-level Nam Powers SES (Np-SES) was derived from parental industry/occupation reported on birth certificates. Neighborhood SES was estimated from average household income of census tract at birth. Cancer incidence was determined by linkage to Utah Cancer Registry records through the Utah Population Database. Hazard ratios (HR) for cancer risk by SES quartile were estimated using Cox proportional hazards regression. RESULTS: Females with low Np-SES at birth had lower risk of breast cancer compared with those in the highest Np-SES group [HRQ1/Q4 = 0.83; 95% confidence interval (CI), 0.72-0.97; HRQ2/Q4 = 0.81; 95% CI, 0.69-0.96]. Np-SES was inversely associated with melanoma (HRQ1/Q4 = 0.81; 95% CI, 0.67-0.98) and prostate cancer (HRQ1/Q4 = 0.70; 95% CI, 0.56-0.88). Women born into lower SES neighborhoods had significantly increased risk for invasive cervical cancer (HRQ1/Q4 = 1.44; 95% CI, 1.12-1.85; HRQ2/Q4 = 1.33; 95% CI, 1.04-1.72). Neighborhood SES had similar effects for melanoma and prostate cancers, but was not associated with female breast cancer. We found no association with SES for pancreas, lung, and colon and rectal cancers. CONCLUSIONS: Individual SES derived from parental occupation at birth was associated with altered risk for several cancer sites. IMPACT: This novel methodology can contribute to improved understanding of the role of early-life SES on cancer risk. Cancer Epidemiol Biomarkers Prev; 26(1); 75-84. (c)2016 AACR. PMID- 27655901 TI - Occurrence of white striping and wooden breast in broilers fed grower and finisher diets with increasing lysine levels. AB - Two experiments were conducted to evaluate the prevalence and severity of white striping (WS) and wooden breast (WB) in breast fillets from broilers fed diets with increasing digestible Lysine (dLys) from 12 to 28 d (Exp. 1) and from 28 to 42 d (Exp. 2). Trials were sequentially conducted using one-d-old male, slow feathering Cobb 500 * Cobb broilers, both with 6 treatments and 8 replicates. Increasing dLys levels were equally spaced from 0.77 to 1.17% in Exp. 1 and from 0.68 to 1.07% in Exp. 2. The lowest dLys diet was not supplemented with L-Lysine (L-Lys) in either one of the studies and all other essential amino acid (AA) met or exceeded current commercial recommendations such that their dietary concentrations did not limit broiler growth. Four birds per pen were randomly selected from each replication and processed at 35 and 42 d in Exp. 1 and Exp. 2, respectively. Deboned breast fillets (Pectoralis major) were submitted to a 3 subject panel evaluation to detect the presence of WS and WB, as well as to provide scores of WS (0-normal, 1-moderate, 2-severe) and WB (0-normal, 1 moderate light, 2-moderate, 3-severe). Increasing the level of dLys had a positive effect on BW, carcass, and breast weight, as well as breast yield. White striping and WB prevalences were 32.3 and 85.9% in Exp. 1 and 87.1 and 89.2% in Exp. 2. Birds fed diets not supplemented with L-Lys had the lowest average WS and WB scores (0.22 and 0.78 in Exp. 1 and 0.61 and 0.68 in Exp. 2). White striping and WB presented linear responses to performance variables in Exp. 1, whereas quadratic responses were observed for all variables in Exp. 2. In conclusion, increasing the level of dLys improved growth performance and carcass traits as well as induced the occurrence and severity of WS and WB lesions. PMID- 27655900 TI - CCR2 deficiency does not provide sustained improvement of muscular dystrophy in mdx5cv mice. AB - Genetic ablation or pharmacologic inhibition of CC chemokine receptor type 2 (CCR2) reduced macrophage (MP) infiltration and improved muscle pathology and function in mdx diaphragm muscle at early stages. We addressed whether CCR2 deficiency resulted in sustained improvement of mdx5cv-Ccr2-/- diaphragm. Compared to mdx5cv controls, CCR2 deficiency in mdx5cv-Ccr2-/- mice markedly reduced intramuscular Ly6Chi MPs at all stages, but it reduced Ly6Clow MPs only at early stages (4 and 9 wk). CCR2 deficiency reduced quadriceps and diaphragm muscle damage and fibrosis at 14 wk but not at 6 mo, and it improved diaphragm muscle regeneration and respiratory function at 14 wk but not at 6 mo. Intramuscular MPs in mdx5cv-Ccr2-/- diaphragm expressed a low level of IL-1beta, IL-6, and IFN-gamma genes, a similar level of TNF-alpha, TGF-beta1, and platelet derived growth factor alpha genes, and a high level of IGF-1 and osteopontin genes compared to mdx5cv controls. Diaphragm fibroblasts at 14 wk showed a similar cell number with a similar level of collagen and profibrogenic growth factor gene expression in mdx5cv-Ccr2-/- and mdx5cv mice. Diaphragm MPs from both mdx5cv-Ccr2-/- and mdx5cv mice stimulated collagen gene expression by cocultured fibroblasts. The findings suggest that CCR2 deficiency does not provide a sustained benefit and that Ly6Clow MPs may contribute to the progressive fibrosis and dysfunction of mdx5cv diaphragm.-Zhao, W., Wang, X., Ransohoff, R. M., Zhou, L. CCR2 deficiency does not provide sustained improvement of muscular dystrophy in mdx5cv mice. PMID- 27655902 TI - Role of surgery in N2 NSCLC: pros. AB - The optimal management of clinical N2 Stage IIIA non-small cell lung cancer is still controversial. For a cure of locally advanced IIIA/N2 non-small cell lung cancer, the control of both local regions and possible distant micrometastases is crucial. Chemotherapy is generally expected to prevent distant recurrence. For local tumor control, radiotherapy or surgery has been adopted singly or in combination. If a complete resection can be safely performed, surgery remains the strongest modality for 'eradicating' local disease. Many retrospective studies have reported a possible survival benefit of induction treatment followed by surgery in selected patients with IIIA/N2 non-small cell lung cancer; however, randomized Phase III trials have failed to demonstrate the superiority of induction treatment followed by surgery over chemoradiotherapy, mainly because of the heterogeneity of the N2 status. IIIA/N2 non-small cell lung cancer consists of a heterogeneous group of disease ranging from microscopically single station to radiologically bulky ipsilateral multi-station mediastinal lymph node involvement. A recent definition proposed by the American College of Chest Physicians classified non-small cell lung cancer based on the N2 status, such as discrete or infiltrative type, and recommendations were made according to this N2 status, with definitive chemoradiotherapy recommended for infiltrative clinical N2 and definitive chemoradiotherapy or induction treatment followed by surgery recommended for other cases. Thus, the introduction of a multimodality treatment strategy seems to be necessary for the improved prognosis of non-small cell lung cancer patients with IIIA/N2 disease. In this review, we discuss the role of surgery and the optimal surgical management for patients with IIIA/N2 non-small cell lung cancer. PMID- 27655903 TI - Preoperative chemoradiotherapy for elderly patients with locally advanced rectal cancer-a real-world outcome study. AB - OBJECTIVE: Preoperative chemoradiotherapy has been established as a standard treatment for locally advanced rectal cancer. It is unclear whether preoperative chemoradiotherapy is truly beneficial in the elderly patients. Our aim was to assess the impact of age on the treatment tolerance and clinical outcomes. METHODS: We retrospectively analyzed 160 consecutive patients with clinical stage T3-4, and/or lymph node positive tumors who received preoperative chemoradiotherapy from May 2003 to December 2010 at a single hospital. Treatment tolerance and outcomes were compared between patients >=70 years (N = 56) and <70 years (N = 104). RESULTS: There was no disparity in the achievement of prescribed radiation dose and dose reduction of chemotherapy between two groups. Pathologic complete response rate (15.6% vs. 16.0%) and sphincter preservation rate (91.1% vs. 95.0%; P = 0.459) were not significantly different. The 3-year disease-free survival of older vs. younger patients was 77.8% vs. 92.3% and 5-year disease free survival was 60.0% vs. 78.6%, respectively (P = 0.023). In multivariable analysis, age was significantly associated with disease-free survival (P = 0.033) but comorbidities were not (P = 0.092). However, both age (hazard ratio, 2.331; P = 0.028) and comorbidities (hazard ratio, 2.772; P = 0.031) were significantly associated with overall survival as well as clinical stage. Anemia was the only adverse effect more prominent in older patients. CONCLUSIONS: Older patients showed non-inferior compliance and equivalent pathologic complete response rates without an increased incidence of treatment complications with preoperative chemoradiotherapy. More comprehensive consideration than age alone is warranted in the decision of applying preoperative chemoradiotherapy to elderly patients with rectal cancer. PMID- 27655904 TI - Treatments and outcomes of advanced/recurrent non-small cell lung cancer harboring the EGFR T790M mutation: a retrospective observational study of 141 patients in Japan. AB - BACKGROUND: The epidermal growth factor receptor (EGFR) T790M mutation is considered the major mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR sensitizing mutations. Although chemotherapy is commonly used for those patients under the condition without T790M-targeted therapy, the clinical outcomes are poorly defined. Therefore, we aimed to reveal the treatment patterns and clinical outcomes in patients with T790M-positive NSCLC. METHODS: We conducted a retrospective observational study at 23 sites in Japan, and 141 patients with T790M-positive advanced/recurrent NSCLC were identified from January 2008 to December 2014. Their records were studied to understand treatment patterns after detection of a T790M mutation and to assess the objective response rate (ORR) and median survival time (MST) to specific treatment modalities. RESULTS: Of 141 patients, 24 had de novo T790M-positive tumors and 117 had acquired T790M positive tumors, with MSTs (95% CI) of 21.4 (12.4-36.7) and 9.1 (6.4-13.9) months, respectively. The most common regimen was platinum-based doublet chemotherapy +/- bevacizumab, which was associated with an ORR/MST of 25.0%/29.1 months, respectively, in patients with de novo T790M mutations, and 22.2%/15.3 months, respectively, in patients with acquired T790M mutations. CONCLUSIONS: This study reveals the treatment patterns and outcomes of NSCLC patients in Japan after detection of the T790M mutation. The most common treatment following detection of the T790M mutation was platinum-based doublet chemotherapy +/- bevacizumab. Platinum-based doublet chemotherapy +/- bevacizumab was moderately effective, indicating the need for targeted therapies for patients with T790M mutation-positive NSCLC. PMID- 27655905 TI - A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study). AB - A randomized phase II/III trial was started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional fluorouracil and folinic acid with oxaliplatin for lower rectal cancer patients with suspected lateral pelvic node metastasis. The standard arm is total mesorectal excision or tumor-specific mesorectal excision with lateral pelvic node dissection (LND) followed by postoperative chemotherapy (modified infusional fluorouracil and folinic acid with oxaliplatin; 12 cycles). The experimental (perioperative chemotherapy) arm is six courses of modified infusional fluorouracil and folinic acid with oxaliplatin before and six courses after total mesorectal excision with lateral pelvic node dissection. The aim of this trial is to confirm the superiority of perioperative chemotherapy. A total of 330 patients will be enrolled over 7 years. The primary endpoint in Phase II part is proportion of R0 resection and that in Phase III part is overall survival. Secondary endpoints are progression-free survival, local progression-free survival, etc. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017603 [http://www.umin.ac.jp/ctr/index-j.htm]. PMID- 27655906 TI - A prediction model of survival for patients with bone metastasis from uterine corpus cancer. AB - OBJECTIVE: The aim of the study was to establish a predictive model of survival period after bone metastasis from endometrial cancer. METHODS: A total of 28 patients with bone metastasis from uterine corpus cancer were included in the study. Data at the time of bone metastasis diagnosis, which included presence of extraskeletal metastasis, performance status, history of any previous radiation/chemotherapy and the number of bone metastases, were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: The most common site of bone metastasis was the pelvis (50.0%), followed by lumbar spine (32.1%), thoracic spine (25.0%) and rib bone (17.9%). The median survival period after bone metastasis was 25 weeks. The overall rate of survival after bone metastasis of the entire cohort was 75.0% at 13 weeks, 46.4% at 26 weeks and 42.9% at 52 weeks. Performance status of 3-4 was confirmed as an independent prognostic factor (Hazard ratio, 3.5; 95% confidence interval, 1.41-8.70) and multiple bone metastases tended to be associated with poor prognosis (Hazard ratio, 2.4; 95% confidence interval, 0.95-5.97). A prognostic score was calculated by adding up the number of these two factors. The 26-week survival rates after bone metastasis were 88.9% for those with a score of 0, 45.5% for those with a score of 1 and 0% for those with a score of 2 (P = 0.0006). CONCLUSIONS: This scoring system can be used to determine the optimal treatment for patients with bone metastasis from endometrial cancer. PMID- 27655908 TI - Incidence rate for uterus cancer in Japanese in Japan and in the United States from the Cancer Incidence in Five Continents. PMID- 27655907 TI - The role of pulmonary resection in tumors metastatic from esophageal carcinoma. AB - OBJECTIVE: The purposes of this study were to determine the role of surgical treatment and to identify factors affecting survival of patients undergoing resection of pulmonary metastatic tumors from esophageal carcinoma. METHODS: We reviewed 33 patients who had undergone resection of pulmonary metastatic tumors from esophageal carcinoma after definitive treatment. RESULTS: The operative morbidity rate was only 5%, no patients died within 30 days after resection, and complete resection was achieved in 30 patients. The overall 1-, 3- and 5-year survival rates after pulmonary metastasectomy were 79.4, 47.8 and 43.0%, respectively, and the median survival time was 17.9 months. The factors found on univariate analysis to affect survival significantly were disease-free interval <16 months and nodal involvement of the primary tumor. The most frequent pattern of initial recurrence after pulmonary resection was distant metastasis (70%). CONCLUSIONS: We demonstrated the safety and effectiveness of surgical resection for selected patients with pulmonary metastatic tumors from esophageal carcinoma. However, with a high recurrence rate in patients with negative prognostic factors, adjuvant systemic chemotherapy after pulmonary resection should be considered. PMID- 27655909 TI - N-Glycosylation influences transport, but not cellular trafficking, of a neuronal amino acid transporter SNAT1. AB - SNAT1 is a system N/A neutral amino acid transporter that primarily expresses in neurons and mediates the transport of l-glutamine (Gln). Gln is an important amino acid involved in multiple cellular functions and also is a precursor for neurotransmitters, glutamate and GABA. In the present study, we demonstrated that SNAT1 is an N-glycoprotein expressed in neurons. We identified three glycosylation sites at asparagine residues 251, 257 and 310 in SNAT1 protein, and that the first two are the primary sites. The biotinylation and confocal immunofluorescence analysis showed that the glycosylation-impaired mutants and deglycosylated SNAT1 were equally capable of expressing on the cell surface. However, l-Gln and 3H-labeled methyl amino isobutyrate (MeAIB) was significantly compromised in N-glycosylation-impaired mutants and deglycosylated SNAT1 when compared with the wild-type control. Taken together, these results suggest that SNAT1 is an N-glycosylated protein with three de novo glycosylation sites and N glycosylation of SNAT1 may play an important role in the transport of substrates across the cell membrane. PMID- 27655911 TI - Stable expression of Shigella dysenteriae serotype 1 O-antigen genes integrated into the chromosome of live Salmonella oral vaccine vector Ty21a. AB - Typhoid fever and shigellosis cause high morbidity and mortality worldwide, yet no anti-Shigella vaccine is currently available. However, to protect against typhoid fever, an approved vaccine, based on the attenuated Salmonella enterica serovar Typhi strain Ty21a is available. We have investigated Ty21a as a live oral vaccine vector for expression of heterologous foreign antigens to protect against other diseases (e.g. shigellosis, anthrax, and plague). Shigella LPS is a potent vaccine antigen for serotype-specific protection against Shigellae. We previously reported the construction of a Ty21a derivative expressing S. sonnei O antigen by insertion of a large (~12.5 kb) operon comprising the S. sonnei O antigen biosynthetic genes into a targeted site within the Ty21a chromosome using modified lambda red recombineering methods. In the current study, S. dysenteriae 1 O-antigen biosynthetic genes from 2 separate genetic loci, rfp and rfb were assembled and inserted into the Ty21a chromosome by lambda red-mediated recombineering to construct strain Ty21a-Sd. To obtain a high level of heterologous LPS expression, the native upstream promoter was replaced with the constitutive lpp promoter, which resulted in Ty21a-Sdl with enhanced heterologous LPS expression. Both Ty21a-Sd and Ty21a-Sdl elicited significant serum antibody responses in mice against both Ty21a and this heterologous Shigella LPS, and conferred protection against virulent S. dysenteriae 1 challenge. This work represents progress toward the goal of a safe and effective vaccine against Shigella. PMID- 27655910 TI - Fluorescence-based rapid measurement of sphingosine-1-phosphate transport activity in erythrocytes. AB - Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal intercellular signal transmitter in the immune system by recruiting lymphocytes from the thymus and secondary lymphoid tissues. The plasma S1P concentration is maintained by the supply of S1P from erythrocytes. Previously, we showed that S1P release from erythrocytes is mediated by an ATP-dependent transporter. In this study, we attempted to establish a rapid and reliable method for measuring the S1P transport activity in erythrocytes by using a fluorescent S1P analog, 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled S1P. NBD-S1P was released from erythrocytes in a time-dependent manner. The NBD-S1P release was reduced after exposure to glyburide, which is an inhibitor of the S1P transporter in erythrocytes. Moreover, the release of NBD-S1P and S1P from erythrocytes was competitively inhibited by intracellular S1P and NBD-S1P, respectively. These results showed that the erythrocyte S1P transporter exports NBD-S1P. We optimized the sample-preparation conditions and lipid extraction to increase the sensitivity of the assay. Furthermore, we successfully measured NBD-S1P release without lipid extraction by decreasing the concentration of BSA in the assay buffer to 0.1%. This method will be useful for the high-throughput screening of S1P transporter inhibitors using conventional fluorometers. PMID- 27655912 TI - Central nervous system infection following vertical transmission of Coxsackievirus B4 in mice. AB - Coxsackie B viruses (CV-B) are important pathogens associated with several central nervous system (CNS) disorders. CV-B are mainly transmitted by the faecal oral route, but there is also evidence for vertical transmission. The outcome of in utero CV-B infections on offspring's CNS is poorly explored. The aim of this study was to investigate vertical transmission of CV-B to the CNS. For this purpose, pregnant Swiss albino mice were intraperitoneally inoculated with CV-B4 E2 at gestational days 10G or 17G. Different CNS compartments were collected and analyzed for virus infection and histopathological changes. Using plaque assays, we demonstrated CV-B4 E2 vertical transmission to offspring's CNS. Viral RNA persisted in the CNS up to 60 days after birth, as evidenced by a sensitive semi nested(sn) reverse transcripton(RT)-PCR method. This was despite infectious particles becoming undetectable at later time points. Persistence was associated with inflammatory lesions, lymphocyte infiltration and viral dsRNA detected by immunohistochemistry. Offspring born to dams mock- or virus-infected at day 17G were challenged by the same virus at day 21 after birth (-+ and ++ groups, respectively). Sn-RT-PCR and histology results compared between both ++ and -+ groups, show that in utero infection did not enhance CNS infection during challenge of the offspring with the same virus. PMID- 27655914 TI - The Protein Tyrosine Phosphatase MEG2 Regulates the Transport and Signal Transduction of Tropomyosin Receptor Kinase A. AB - Protein tyrosine phosphatase MEG2 (PTP-MEG2) is a unique nonreceptor tyrosine phosphatase associated with transport vesicles, where it facilitates membrane trafficking by dephosphorylation of the N-ethylmaleimide-sensitive fusion factor. In this study, we identify the neurotrophin receptor TrkA as a novel cargo whose transport to the cell surface requires PTP-MEG2 activity. In addition, TrkA is also a novel substrate of PTP-MEG2, which dephosphorylates both Tyr-490 and Tyr 674/Tyr-675 of TrkA. As a result, overexpression of PTP-MEG2 down-regulates NGF/TrkA signaling and blocks neurite outgrowth and differentiation in PC12 cells and cortical neurons. PMID- 27655913 TI - Actin-based motility of bacterial pathogens: mechanistic diversity and its impact on virulence. AB - A diverse spectrum of intracellular bacterial pathogens that inhabit the cytosol have evolved the ability to polymerize actin on their surface to power intracellular actin-based motility (ABM). These include species of Listeria, Burkholderia and Rickettsia, as well as Shigella and Mycobacteria Here, we provide an overview of the roles of bacterial ABM in survival and virulence. Moreover, we survey the molecular mechanisms of actin polymerization in host cells and describe how bacterial pathogens mimic or harness the full diversity of these mechanisms for ABM. Finally, we present ABM through a new lens by comparing motility mechanisms between related species of Listeria, Burkholderia, and Rickettsia Through these comparisons, we hope to illuminate how exploitation of different actin polymerization mechanisms influences ABM as well as pathogenicity and virulence in humans and other animals. PMID- 27655915 TI - Very Low Density Lipoprotein Assembly Is Required for cAMP-responsive Element binding Protein H Processing and Hepatic Apolipoprotein A-IV Expression. AB - Hepatic apolipoprotein A-IV (apoA-IV) expression is correlated with hepatic triglyceride (TG) content in mouse models of chronic hepatosteatosis, and steatosis-induced hepatic apoA-IV gene expression is regulated by nuclear transcription factor cAMP-responsive element-binding protein H (CREBH) processing. To define what aspects of TG homeostasis regulate hepatic CREBH processing and apoA-IV gene expression, several mouse models of attenuated VLDL particle assembly were subjected to acute hepatosteatosis induced by an overnight fast or short term ketogenic diet feeding. Compared with chow-fed C57BL/6 mice, fasted or ketogenic diet-fed mice displayed increased hepatic TG content, which was highly correlated (r2 = 0.95) with apoA-IV gene expression, and secretion of larger, TG-enriched VLDL, despite a lower rate of TG secretion and a similar or reduced rate of apoB100 secretion. When VLDL particle assembly and secretion was inhibited by hepatic shRNA-induced apoB silencing or genetic or pharmacologic reduction in microsomal triglyceride transfer protein (MTP) activity, hepatic TG content increased dramatically; however, CREBH processing and apoA-IV gene expression were attenuated compared with controls. Adenovirus-mediated reconstitution of MTP expression proportionately restored CREBH processing and apoA-IV expression in liver-specific MTP knock-out mice. These results reveal that hepatic TG content, per se, does not regulate CREBH processing. Instead, TG mobilization into the endoplasmic reticulum for nascent VLDL particle assembly activates CREBH processing and enhances apoA-IV gene expression in the setting of acute steatosis. We conclude that VLDL assembly and CREBH activation play key roles in the response to hepatic steatosis by up-regulating apoA-IV and promoting assembly and secretion of larger, more TG-enriched VLDL particles. PMID- 27655918 TI - Editor's Choice- Impact of immediate multivessel percutaneous coronary intervention versus culprit lesion intervention on 1-year outcome in patients with acute myocardial infarction complicated by cardiogenic shock: Results of the randomised IABP-SHOCK II trial. AB - BACKGROUND: Current guidelines recommend immediate multivessel percutaneous coronary intervention (PCI) in patients with cardiogenic shock, despite the lack of randomised trials. We sought to investigate the use and impact on outcome of multivessel PCI in comparison to culprit lesion only PCI in a retrospective analysis in patients with cardiogenic shock complicating acute myocardial infarction. METHODS AND RESULTS: In the randomised IABP-SHOCK II trial, investigating the effect of intra-aortic balloon pump on outcome, 451 (75%) of the total of 600 patients had multivessel coronary artery disease and underwent PCI. Immediate multivessel PCI was performed in 167 (37%) patients. TIMI 3 patency after PCI in all treated vessels was observed in 83.2% versus 79.0% of patients after multivessel versus culprit lesion PCI, respectively. The 30-day (44.9% vs. 42.3%) and 12-month (54.8% vs. 52.7%) mortality rates did not significantly differ between the two groups. In the multivariate analysis multivessel PCI was not associated with an improved mortality after 12 months (odds ratio 0.92, 95% confidence intervals 0.69-1.21). CONCLUSION: In this retrospective analysis of the largest randomised study in cardiogenic shock immediate multivessel PCI was used in approximately one third of patients with cardiogenic shock. There was no benefit with immediate multivessel PCI in comparison to culprit lesion only PCI. Therefore a randomised trial is needed to determine the definitive role of multivessel PCI in cardiogenic shock. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT00491036. PMID- 27655916 TI - Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses. AB - Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery. Dietary and pharmacological manipulation of zebrafish larvae demonstrated that these subcellular changes are specific to triglyceride absorption. The transcriptional changes that occur simultaneously with these morphological changes were determined using RNA sequencing, revealing a cohort of up-regulated genes associated with lipid droplet formation and lipid transport via lipoprotein particles. Using a microsomal triglyceride transfer protein (MTP) inhibitor to block beta-lipoprotein particle formation, we demonstrate that the transcriptional response to a high-fat meal is associated with the transfer of ER triglyceride to nascent beta-lipoproteins, possibly through the activation of Creb3l3/cyclic AMP-responsive element-binding protein. These data suggest that a transient increase in ER lipids is the likely mediator of the initial physiological response of intestinal enterocytes to dietary lipid. PMID- 27655917 TI - Regulation of Integrin alpha6 Recycling by Calcium-independent Phospholipase A2 (iPLA2) to Promote Microglia Chemotaxis on Laminin. AB - Microglia are the immune effector cells that are activated in response to pathological changes in the central nervous system. Microglial activation is accompanied by the alteration of integrin expression on the microglia surface. However, changes of integrin expression upon chemoattractant (ADP) stimulation still remain unknown. In this study, we investigated whether ADP induces the alteration of integrin species on the cell surface, leading to changes in chemotactic ability on different extracellular matrix proteins. Flow cytometry scans and on-cell Western assays showed that ADP stimulation induced a significant increase of alpha6 integrin-GFP, but not alpha5, on the surface of microglia cells. Microglia also showed a greater motility increase on laminin than fibronectin after ADP stimulation. Time lapse microscopy and integrin endocytosis assay revealed the essential role of calcium-independent phospholipase A2 activity for the recycling of alpha6 integrin-GFP from the endosomal recycling complex to the plasma membrane. Lack of calcium-independent phospholipase A2 activity caused a reduced rate of focal adhesion formation on laminin at the leading edge. Our results suggest that the alteration of integrin mediated adhesion may regulate the extent of microglial infiltration into the site of damage by controlling their chemotactic ability. PMID- 27655919 TI - Experience with indwelling pleural catheters in the treatment of recurrent pleural effusions. AB - Recurrent pleural effusions are frequently encountered in clinical practice. Whether malignant or nonmalignant, they often pose a challenge to the practicing clinician. When they recur, despite optimum medical therapy of the underlying condition and repeated thoracenteses, more invasive definitive approaches are usually required. Since its introduction in 1997, the PleurX catheter became the preferred method to treat recurrent malignant pleural effusions. Since then, a number of publications have documented its utility in managing recurrent nonmalignant pleural effusions. The purpose of this paper is to review the use of the PleurX catheter in recurrent pleural effusions. PMID- 27655928 TI - Molecularly Defined Subplate Neurons Project Both to Thalamocortical Recipient Layers and Thalamus. AB - In mammals, subplate neurons (SPNs) are among the first generated cortical neurons. While most SPNs exist only transiently during development, a number of SPNs persist among adult Layer 6b (L6b). During development, SPNs receive thalamic and intra-cortical input, and primarily project to Layer 4 (L4). SPNs are critical for the anatomical and functional development of thalamocortical connections and also pioneer corticothalamic projections. Since SPNs are heterogeneous, SPN subpopulations might serve different roles. Here, we investigate the connectivity of one subpopulation, complexin-3 (Cplx3)-positive SPNs (Cplx3-SPNs), in mouse whisker somatosensory (barrel) cortex (S1). We find that many Cplx3-SPNs survive into adulthood and become a subpopulation of L6b. Cplx3-SPNs axons project to thalamorecipient layers, that is, L4, 5a, and 1. The L4 projections are biased towards the septal regions between barrels in the second postnatal week. Thus, S1 Cplx3-SPN targets co-localize with the eventual projections of the medial posterior thalamic nucleus (POm). In addition to their cortical targets, Cplx3-SPNs also extend long-range axons to several thalamic nuclei, including POm. Thus, Cplx3-SPN/L6b neurons are associated with paralemniscal pathways and can potentially directly link thalamocortical and corticothalamic circuits. This suggests an additional key role for SPNs in the establishment and maintenance of thalamocortical processing. PMID- 27655929 TI - Gradual Development of Visual Texture-Selective Properties Between Macaque Areas V2 and V4. AB - Complex shape and texture representations are known to be constructed from V1 along the ventral visual pathway through areas V2 and V4, but the underlying mechanism remains elusive. Recent study suggests that, for processing of textures, a collection of higher-order image statistics computed by combining V1 like filter responses serves as possible representations of textures both in V2 and V4. Here, to gain a clue for how these image statistics are processed in the extrastriate visual areas, we compared neuronal responses to textures in V2 and V4 of macaque monkeys. For individual neurons, we adaptively explored their preferred textures from among thousands of naturalistic textures and fitted the obtained responses using a combination of V1-like filter responses and higher order statistics. We found that, while the selectivity for image statistics was largely comparable between V2 and V4, V4 showed slightly stronger sensitivity to the higher-order statistics than V2. Consistent with that finding, V4 responses were reduced to a greater extent than V2 responses when the monkeys were shown spectrally matched noise images that lacked higher-order statistics. We therefore suggest that there is a gradual development in representation of higher-order features along the ventral visual hierarchy. PMID- 27655931 TI - Resting-state Functional Connectivity is an Age-dependent Predictor of Motor Learning Abilities. AB - This magnetoencephalography study investigates how ageing modulates the relationship between pre-learning resting-state functional connectivity (rsFC) and subsequent learning. Neuromagnetic resting-state activity was recorded 5 min before motor sequence learning in 14 young (19-30 years) and 14 old (66-70 years) participants. We used a seed-based beta-band power envelope correlation approach to estimate rsFC maps, with the seed located in the right primary sensorimotor cortex. In each age group, the relation between individual rsFC and learning performance was investigated using Pearson's correlation analyses. Our results show that rsFC is predictive of subsequent motor sequence learning but involves different cross-network interactions in the two age groups. In young adults, decreased coupling between the sensorimotor network and the cortico-striato cerebellar network is associated with better motor learning, whereas a similar relation is found in old adults between the sensorimotor, the dorsal-attentional and the DMNs. Additionally, age-related correlational differences were found in the dorsolateral prefrontal cortex, known to subtend attentional and controlled processes. These findings suggest that motor skill learning depends-in an age dependent manner-on subtle interactions between resting-state networks subtending motor activity on the one hand, and controlled and attentional processes on the other hand. PMID- 27655932 TI - The "Creative Right Brain" Revisited: Individual Creativity and Associative Priming in the Right Hemisphere Relate to Hemispheric Asymmetries in Reward Brain Function. AB - The idea that creativity resides in the right cerebral hemisphere is persistent in popular science, but has been widely frowned upon by the scientific community due to little empirical support. Yet, creativity is believed to rely on the ability to combine remote concepts into novel and useful ideas, an ability which would depend on associative processing in the right hemisphere. Moreover, associative processing is modulated by dopamine, and asymmetries in dopamine functionality between hemispheres may imbalance the expression of their implemented cognitive functions. Here, by uniting these largely disconnected concepts, we hypothesize that relatively less dopamine function in the right hemisphere boosts creativity by releasing constraining effects of dopamine on remote associations. Indeed, participants with reduced neural responses in the dopaminergic system of the right hemisphere (estimated by functional MRI in a reward task with positive and negative feedback), displayed higher creativity (estimated by convergent and divergent tasks), and increased associative processing in the right hemisphere (estimated by a lateralized lexical decision task). Our findings offer unprecedented empirical support for a crucial and specific contribution of the right hemisphere to creativity. More importantly our study provides a comprehensive view on potential determinants of human creativity, namely dopamine-related activity and associative processing. PMID- 27655930 TI - Anterior Cingulate Pathways May Affect Emotions Through Orbitofrontal Cortex. AB - The anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) are associated with emotional regulation. These regions are old in phylogeny and have widespread connections with eulaminate neocortices, intricately linking areas associated with emotion and cognition. The ACC and pOFC have distinct cortical and subcortical connections and are also interlinked, but the pattern of their connections-which may be used to infer the flow of information between them-is not well understood. Here we found that pathways from ACC area 32 innervated all pOFC areas with a significant proportion of large and efficient terminals, seen at the level of the system and the synapse. The pathway from area 32 targeted overwhelmingly elements of excitatory neurons in pOFC, with few postsynaptic sites found on presumed inhibitory neurons. Moreover, pathways from area 32 originated mostly in the upper layers and innervated preferentially the middle deep layers of the least differentiated pOFC areas, in a pattern reminiscent of feedforward communication. Pathway terminations from area 32 overlapped in the deep layers of pOFC with output pathways that project to the thalamus and the amygdala, and may have cascading downstream effects on emotional and cognitive processes and their disruption in psychiatric disorders. PMID- 27655935 TI - Controversies in MS: All relapsing multiple sclerosis patients should be managed at a specialist clinic - Combine the best of two worlds! PMID- 27655933 TI - Genetic Labeling of Nuclei-Specific Thalamocortical Neurons Reveals Putative Sensory-Modality Specific Genes. AB - The thalamus is a central brain structure with topographically ordered long-range axonal projections that convey sensory information to the cortex via distinct nuclei. Although there is an increasing knowledge about genes important for thalamocortical (TC) development, the identification of genetic landmarks of the distinct thalamic nuclei during the embryonic development has not been addressed systematically. Indeed, a more comprehensive understanding of how the axons from the individual nuclei find their way and connect to their corresponding cortical area is called for. Here, we used a genetic dual labeling strategy in mice to purify distinct principal sensory thalamic neurons. Subsequent genome-wide transcriptome profiling revealed genes specifically expressed in each nucleus during embryonic development. Analysis of regulatory regions of the identified genes revealed key transcription factors and networks that likely underlie the specification of individual sensory-modality TC connections. Finally, the importance of correct axon targeting for the specific sensory-modality population transcriptome was evidenced in a Sema6A mutant, in which visual TC axons are derailed at embryonic life. In sum, our data determined the developmental transcriptional profile of the TC neurons that will eventually support sensory processing. PMID- 27655934 TI - The Child Obesity Epidemic in Saudi Arabia: A Review of the Literature. AB - PURPOSE: To examine prevalence, nutrition and activity, and overweight and obesity prevention and management in Saudi Arabia. DESIGN: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria, PubMed, Web of Science, PyschINFO, Global Health, Family Studies Worldwide, Middle Eastern Studies, and Sociological Abstracts was searched from January 1, 2003 to January 31, 2016. Inclusion criteria included peer-reviewed articles published in Arabic and English that focused on prevalence, overweight or obesity in children 2 to 20 years of age, body mass index percentile, and interventions. FINDINGS: Three themes were identified: epidemiological features, where the eastern region had the highest prevalence of overweight and obesity, risk factors, which included higher parental education, and lifestyle factors, which included increased consumption of calorie-dense food and a sedentary lifestyle. CONCLUSION: Childhood obesity is increasing in Saudi Arabia at an alarming rate. IMPLICATIONS FOR PRACTICE: Practitioners need to consider the cultural influences of the increasing obesity epidemic in Saudi Arabia. PMID- 27655936 TI - Direct visualization of lithium via annular bright field scanning transmission electron microscopy: a review. AB - Annular bright field (ABF) scanning transmission electron microscopy has proven able to directly image lithium columns within crystalline environments, offering much insight into the structure and properties of lithium-ion battery materials. We summarize the image formation mechanisms underpinning ABF imaging, review the experimental application of this technique to imaging lithium in materials and overview the conditions that help maximize the visibility of lithium columns. PMID- 27655937 TI - Electron microscopic study of capillary network remodeling in the extensor digitorum longus muscle of normal adult rat. AB - Capillary networks demonstrate structural changes during maturation, aging, vascular disease, and cancer. Their morphological structure and function have an important influence on each other. Understanding the process of morphological vascular changes in the capillary network with advancing age may help overcome fatal vascular diseases. Aging-related structural changes of the capillary segments may accompany degeneration and regeneration of muscle fibers and serve to remodel the capillary network as a means of adapting to the changing environment. However, difficulty in obtaining human samples has hampered clarification of these microstructural changes. Herein, we examined serial ultrathin sections of capillary segments in the extensor digitorum longus muscle of normal mature (12 months old) rats in an attempt to analyze their structural changes. After bifurcation, a minimum of one capillary segment was filled with erythrocytes and was found to have fenestrations and plural endothelial disruptions, or pores, at the fenestrated portions. Some of the stagnated erythrocytes demonstrated extended protrusions, and their processes appeared to penetrate the basal lamina through the pores. These findings can also show that capillary segments are involved in partial remodeling of the capillary network. A better understanding of age-related structural changes of the capillary networks will help in fine-tuning novel vascular therapy for not only several fatal vascular diseases but also malignant tumors. PMID- 27655938 TI - Detection of local chemical states of lithium and their spatial mapping by scanning transmission electron microscopy, electron energy-loss spectroscopy and hyperspectral image analysis. AB - Advancements in the field of renewable energy resources have led to a growing demand for the analysis of light elements at the nanometer scale. Detection of lithium is one of the key issues to be resolved for providing guiding principles for the synthesis of cathode active materials, and degradation analysis after repeated use of those materials. We have reviewed the different techniques currently used for the characterization of light elements such as high-resolution transmission electron microscopy, scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS). In the present study, we have introduced a methodology to detect lithium in solid materials, particularly for cathode active materials used in lithium-ion battery. The chemical states of lithium were isolated and analyzed from the overlapping multiple spectral profiles, using a suite of STEM, EELS and hyperspectral image analysis. The method was successfully applied in the chemical state analyses of hetero-phases near the surface and grain boundary regions of the active material particles formed by chemical reactions between the electrolyte and the active materials. PMID- 27655939 TI - NHERF1 in Microvilli of Vomeronasal Sensory Neurons. AB - In most mammals, the vomeronasal system detects a variety of (semio)chemicals that mediate olfactory-driven social and sexual behaviors. Vomeronasal chemosensation depends on G protein-coupled receptors (V1R, V2R, and FPR-rs) that operate at remarkably low stimulus concentrations, thus, indicating a highly sensitive and efficient signaling pathway. We identified the PDZ domain containing protein, Na+/H+ exchanger regulatory factor-1 (NHERF1), as putative molecular organizer of signal transduction in vomeronasal neurons. NHERF1 is a protein that contains 2 PDZ domains and a carboxy-terminal ezrin-binding domain. It localizes to microvilli of vomeronasal sensory neurons and interacts with V1Rs. Furthermore, NHERF1 and Galphai2 are closely colocalized. These findings open up new aspects of the functional organization and regulation of vomeronasal signal transduction by PDZ scaffolding proteins. PMID- 27655940 TI - Individual Differences in Verbal and Non-Verbal Affective Responses to Smells: Influence of Odor Label Across Cultures. AB - Olfactory perception is highly variable from one person to another, as a function of individual and contextual factors. Here, we investigated the influence of 2 important factors of variation: culture and semantic information. More specifically, we tested whether cultural-specific knowledge and presence versus absence of odor names modulate odor perception, by measuring these effects in 2 populations differing in cultural background but not in language. Participants from France and Quebec, Canada, smelled 4 culture-specific and 2 non-specific odorants in 2 conditions: first without label, then with label. Their ratings of pleasantness, familiarity, edibility, and intensity were collected as well as their psychophysiological and olfactomotor responses. The results revealed significant effects of culture and semantic information, both at the verbal and non-verbal level. They also provided evidence that availability of semantic information reduced cultural differences. Semantic information had a unifying action on olfactory perception that overrode the influence of cultural background. PMID- 27655941 TI - Left anteromedial strangulated congenital diaphragmatic hernia in an 11-year-old child: a case report. PMID- 27655942 TI - A study on nutritional status of school-going adolescents in Aligarh, India. AB - Adolescence is a highly vulnerable period for malnutrition. This study was based on a Global School Health Survey methodology in the 13-15-year age group; employing WHO AnthroPlus to evaluate the nutritional status, find the prevalence of both extremes of malnutrition, compare with the growth curves and to find its sociodemographic correlates. A total of 1456 students were sampled and the mean BMI for age Z score was found to be -0.11. The prevalence of overweight and obese were 11.95% and 2.27%, respectively, whereas 2.75% suffered from thinness, defined as BMI for age <2 standard deviations. The prevalence of being overweight and obese was associated with a higher standard of living, a higher education of father or mother, working mothers and father's occupation being service/business. The evident double burden of malnutrition presages a large public health burden in future, requiring interventional attention. PMID- 27655943 TI - Proteinuria in HIV-infected Indian children. AB - Chronic kidney disease (CKD) is a major cause of morbidity and mortality among individuals with HIV infection. Screening for proteinuria in HIV-infected children will help in early detection and treatment, and thus prevention and progression to CKD to end-stage kidney disease (ESRD). We screened 139 HIV infected children aged 18 months to 18 years for proteinuria by urinary dipstick and confirmed by spot urine protein-to-creatinine ratio. If proteinuria was absent by the above methods, patients were screened for microalbuminuria by urinary albumin to creatinine ratio. We found proteinuria in 11.5% and microalbuminuria in 10.6% of our study population. The prevalence of proteinuria was higher in the advanced stages; 8.05% in stage 1, 12.12% in stage 2 and 26.32% in stages 3 + 4. PMID- 27655944 TI - Donor Preference Meets Heterochromatin: Moonlighting Activities of a Recombinational Enhancer in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, a small, intergenic region known as the recombination enhancer regulates donor selection during mating-type switching and also helps shape the conformation of chromosome III. Using an assay that detects transient losses of heterochromatic repression, we found that the recombination enhancer also acts at a distance in cis to modify the stability of gene silencing. In a mating-type-specific manner, the recombination enhancer destabilized the heterochromatic repression of a gene located ~17 kbp away. This effect depended on a subregion of the recombination enhancer that is largely sufficient to determine donor preference. Therefore, this subregion affects both recombination and transcription from a distance. These observations identify a rare example of long-range transcriptional regulation in yeast and raise the question of whether other cis elements also mediate dual effects on recombination and gene expression. PMID- 27655945 TI - Genetic Mapping by Bulk Segregant Analysis in Drosophila: Experimental Design and Simulation-Based Inference. AB - Identifying the genomic regions that underlie complex phenotypic variation is a key challenge in modern biology. Many approaches to quantitative trait locus mapping in animal and plant species suffer from limited power and genomic resolution. Here, I investigate whether bulk segregant analysis (BSA), which has been successfully applied for yeast, may have utility in the genomic era for trait mapping in Drosophila (and other organisms that can be experimentally bred in similar numbers). I perform simulations to investigate the statistical signal of a quantitative trait locus (QTL) in a wide range of BSA and introgression mapping (IM) experiments. BSA consistently provides more accurate mapping signals than IM (in addition to allowing the mapping of multiple traits from the same experimental population). The performance of BSA and IM is maximized by having multiple independent crosses, more generations of interbreeding, larger numbers of breeding individuals, and greater genotyping effort, but is less affected by the proportion of individuals selected for phenotypic extreme pools. I also introduce a prototype analysis method for simulation-based inference for BSA mapping (SIBSAM). This method identifies significant QTL and estimates their genomic confidence intervals and relative effect sizes. Importantly, it also tests whether overlapping peaks should be considered as two distinct QTL. This approach will facilitate improved trait mapping in Drosophila and other species for which hundreds or thousands of offspring (but not millions) can be studied. PMID- 27655947 TI - Sutureless open vascular anastomosis connector: An experimental study. AB - The objective of this study was to assess the safety of a new developed sutureless vascular adapter system in a porcine model. In five pigs, 4-cm-long polyester prosthesis (6 mm diameter) were implanted and anastomosed with the newly developed adapter proximally and suture anastomosis distally. The integration of the adapter was investigated in comparison to the suture anastomosis. These investigations were performed by light microscopy and scanning electron microscopy. Median operative time for performing the adapter anastomosis was significantly shorter compared to suture anastomosis (66 s vs. 246 s, p < 0.05). Median estimated blood loss during adapter anastomosis implementation was 22.5 mL (range 19.0-25.0 mL) compared to 48.2 mL (range 45.4-63.5 mL, p < 0.05). In five hand-sewn anastomoses, overall eight additional stitches were necessary whereas all adapter anastomoses showed primary leak tightness. This in vivo study shows the technical feasibility of the newly developed adapter. PMID- 27655946 TI - Incorporating Functional Annotations for Fine-Mapping Causal Variants in a Bayesian Framework Using Summary Statistics. AB - Functional annotations have been shown to improve both the discovery power and fine-mapping accuracy in genome-wide association studies. However, the optimal strategy to incorporate the large number of existing annotations is still not clear. In this study, we propose a Bayesian framework to incorporate functional annotations in a systematic manner. We compute the maximum a posteriori solution and use cross validation to find the optimal penalty parameters. By extending our previous fine-mapping method CAVIARBF into this framework, we require only summary statistics as input. We also derived an exact calculation of Bayes factors using summary statistics for quantitative traits, which is necessary when a large proportion of trait variance is explained by the variants of interest, such as in fine mapping expression quantitative trait loci (eQTL). We compared the proposed method with PAINTOR using different strategies to combine annotations. Simulation results show that the proposed method achieves the best accuracy in identifying causal variants among the different strategies and methods compared. We also find that for annotations with moderate effects from a large annotation pool, screening annotations individually and then combining the top annotations can produce overly optimistic results. We applied these methods on two real data sets: a meta-analysis result of lipid traits and a cis-eQTL study of normal prostate tissues. For the eQTL data, incorporating annotations significantly increased the number of potential causal variants with high probabilities. PMID- 27655948 TI - Threatened limb from stingray injury. AB - We present the case of a 43-year-old female who suffered a stingray injury to her left ankle. The sting caused occlusion of the dorsalis pedis artery, causing dry gangrene of the medial forefoot. A below knee amputation was recommended but she was transferred for a second opinion. A Prostaglandin E1 infusion was commenced, resulting in alleviation of pain and improvement in perfusion. Amputation of great and second toes was performed, with the head of the first metatarsal preserved and covered via a cross-over skin flap raised from the contralateral leg. Achilles tendon lengthening was then performed to return the foot to a functional position. This case serves to highlight the utility of prostaglandin infusion, and the requirement for a multidisciplinary approach to critical limb ischemia in order to avoid major amputation. PMID- 27655949 TI - The Effects of Life Events and Socioeconomic Position in Childhood and Adulthood on Successful Aging. AB - Objectives: Building on social stress theory, this study has 2 aims. First, we aim to estimate the effects of stressful life events in childhood and adulthood on Successful Aging (SA). Second, we examine how unequal exposure to such life events between individuals with different socioeconomic position (SEP) contributes to socioeconomic inequalities in SA. Method: We used 16-year longitudinal data from 2,185 respondents aged 55-85 years in 1992 in the Dutch nationally representative Longitudinal Aging Study Amsterdam. Measurement of SA was based on earlier work, in which we integrated trajectories in 9 indicators of functioning into an index of SA. Using path analysis, we investigated direct and indirect effects of parental and adulthood SEP as well as of self-reported childhood and adulthood life events on SA. Results: Almost all included life events had negative direct effects on SA. Parental SEP had no direct effect on SA, whereas adulthood SEP had. Higher Parental SEP increased the likelihood of parental problems and parental death in childhood, resulting in negative indirect effects on SA. Higher adulthood SEP had both positive and negative indirect effects on SA, through increasing the likelihood of divorce and unemployment, but decreasing the likelihood of occupational disability. Discussion: SEP and particular stressful life events are largely, but not entirely independent predictors of SA. We found that high and low SEP may increase exposure to particular events that negatively affect SA. Findings suggest that low (childhood) SEP and stressful life events are interrelated factors that may limit individual opportunities to age successfully. PMID- 27655951 TI - Incidence and Risk Factors for Stroke Among 14 European Countries. AB - Background This study compared the risk factors for and incidence of stroke among 14 European countries by using the Survey of Health, Aging, and Retirement in Europe (SHARE). Methods The analysis was based on data collected during 2006 to 2007 from Wave 2 of SHARE and panel data from respondents interviewed during 2004 to 2005. Results and Conclusion The highest stroke incidence rates were found in Denmark, Poland, and Sweden; these incidence rates were more than double that of Spain. Stroke was mostly associated with elderly people (age, >=65 years) in Sweden, France, Switzerland, the Czech Republic, and Greece. In addition, stroke incidence was high among young males (age, <65 years) in Italy and elderly males in Germany and Switzerland. A negative association was found between stroke and vigorous exercise for younger people in Sweden and elderly people in Poland, whereas moderate exercise was significantly associated with stroke only for elderly Belgians, Greeks, and Irish. PMID- 27655950 TI - Successful Aging Among African American Older Adults With Type 2 Diabetes. AB - Objectives: Rowe and Kahn's concept of successful aging remains an important model of well-being; additional research is needed, however, to identify how economically and socially disadvantaged older adults experience well-being, including the role of life events. The findings presented here help address this gap by examining the subjective construction of well-being among urban African American adults (age >= 50) with Type 2 diabetes. Method: As part of the National Institute on Aging-funded Subjective Experience of Diabetes among Urban Older Adults study, ethnographers interviewed African American older adults with diabetes (n = 41) using an adaptation of the McGill Illness Narrative Interview. Data were coded using an inductively derived codebook. Codes related to aging, disease prognosis, and "worldview" were thematically analyzed to identify constructions of well-being. Results: Participants evaluate their well-being through comparisons to the past and to the illnesses of friends and family. Diabetes self-care motivates social engagement and care of others. At times, distrust of medical institutions means well-being also is established through nonadherence to suggested biomedical treatment. Discussion: Hardship and illness in participants' lives frame their diabetes experience and notions of well-being. Providers need to be aware of the social, economic, and political lenses shaping diabetes self-management and subjective well-being. PMID- 27655952 TI - Age Differences in Information Use While Making Decisions: Resource Limitations or Processing Differences? AB - Recent research on the decision-making abilities of older adults has shown that they use less information than young adults. One explanation ascribes this age difference to reductions in cognitive abilities with age. The article includes three experimental studies that focused on determining the conditions in which older and young adults would display dissimilar information processing characteristics. Findings from Studies 1 and 2 demonstrated that older adults are not necessarily at greater disadvantage than young adults in decision contexts that demand more information processing resources. Findings from Study 3 indicated that older adults when faced with decisions that require greater processing are likely to use a strategy that reduces the amount of information needed, whereas younger adults rely on strategies that utilize more resources. Combined the findings indicate that older adults change their decision-making strategies based on the context and information provided. Furthermore, support is provided for processing difference. PMID- 27655953 TI - Social Support and Attitudes to Aging in Later Life. AB - Negative attitudes to aging are a risk factor for poor health and well-being. The current study sought to examine satisfaction with social support as a potentially modifiable factor that might facilitate the development of more positive attitudes to aging. A convenience sample of 501 older respondents (Mage = 72.06) reported on frequency of social support and their satisfaction with it, as well as completing a rating of attachment (model of the self and others), a measure of attitudes to aging, and a number of background measures. Results indicated that better subjective health, younger age, and greater satisfaction with social support were all significant predictors of more positive attitudes to aging, while frequency of social support was not. Model of the self accounted for some variation in satisfaction with social support. Interventions to increase satisfaction with social support in later life, recognizing individual differences and attachment styles, may improve attitudes to aging and further support health and well-being. PMID- 27655954 TI - Perceived Risk of Death in Older Primary Care Patients. AB - There is a large gap between life expectancy and healthy life years at age 65. To reduce this gap, it is necessary that people with medical concerns perceived at higher risk of adverse outcomes are readily identified and treated. The same goes for the need to implement prevention plans. The main objectives of this study are to, in a first step, (a) estimate the percentage of medical concerns, (b) identify factors associated with this concern; in a second step, (c) estimate the perceived risk of death, and (d) evaluate the ability of medical concerns to predict this risk. Results show that the existence and severity of medical concerns are crucial in the prediction of perceived risk of death. Early identification of severity of medical concerns and the availability and adequacy of informal caregiving should allow healthcare professionals to promptly initiate an appropriate assessment and treatment of older patients. PMID- 27655955 TI - Friendship Repertoires and Care Arrangement: A Praxeological Approach. AB - Friends are important companions and serve as sources for diverse dimensions of social support, including elderly care. Rather than researching populations that have already established care arrangements including friends, the author seeks to understand relationship systems with a focus on the inner logic friendship to consequently describe and understand involved care arrangements, be it with family members or friends. To illustrate the diversity of friendship repertoires, qualitative interviews with older adult Germans are analyzed regarding cognitive concepts of friendships in contrast to familiar ties as well as social practices around relationship systems. While some repertoires successfully include chosen ties in their care arrangements, others not only focus on family, they do not wish to receive care from friends. The article's praxeological approach highlights the need to reflect habitual differences when thinking about elderly informal care arrangements. PMID- 27655957 TI - The Benefits of Savoring Life: Savoring as a Moderator of the Relationship Between Health and Life Satisfaction in Older Adults. AB - We investigated the protective impact of savoring capacity on the relationship between physical health and psychological well-being among older adults. A total of 266 adults over 55 years old ( Mean = 73.4 years) completed measures of savoring ability, self-reported health, and life satisfaction. Savoring ability moderated the relationship between health and life satisfaction in older adults. Among people with less savoring ability, poor health was associated with lower life satisfaction. In contrast, people with greater savoring ability maintained higher life satisfaction, regardless of their level of health. These effects were consistent across a variety of different aspects of health, including general health, pain, limitations due to physical health, energy, and social functioning. These findings have direct implications for developing positive interventions to support the psychological well-being of older adults. PMID- 27655959 TI - Word Adjacency Graph Modeling: Separating Signal From Noise in Big Data. AB - There is a need to develop methods to analyze Big Data to inform patient-centered interventions for better health outcomes. The purpose of this study was to develop and test a method to explore Big Data to describe salient health concerns of people with epilepsy. Specifically, we used Word Adjacency Graph modeling to explore a data set containing 1.9 billion anonymous text queries submitted to the ChaCha question and answer service to (a) detect clusters of epilepsy-related topics, and (b) visualize the range of epilepsy-related topics and their mutual proximity to uncover the breadth and depth of particular topics and groups of users. Applied to a large, complex data set, this method successfully identified clusters of epilepsy-related topics while allowing for separation of potentially non-relevant topics. The method can be used to identify patient-driven research questions from large social media data sets and results can inform the development of patient-centered interventions. PMID- 27655960 TI - Quality Improvement Curriculum for Physical Medicine and Rehabilitation Residents: A Needs Assessment. AB - This needs assessment survey of physical medicine and rehabilitation (PM&R) program directors (PDs) from Accreditation Council for Graduate Medical Education accredited programs aimed to (1) describe current quality improvement (QI) training, (2) characterize PDs' perceptions of their own and their faculty's QI knowledge and skill, and (3) determine PDs' opinions of optimal QI training to inform the development of a future QI curriculum. Descriptive statistics were used for data analysis. Forty-five percent of PDs (35/78) responded. All programs had QI education and required QI project participation; however, the quantity and types of learning experiences varied greatly. PDs assessed their ability as less than proficient to teach QI (67%) and lead a project (57%), and rated 60% of their faculty as having novice or advanced beginner QI skills. PDs reported 31% of graduating residents had less than competent QI skills. Almost all PDs were interested in a standardized QI curriculum. PMID- 27655961 TI - Superentrainment of muscle sympathetic nerve activity during sinusoidal galvanic vestibular stimulation. AB - Sinusoidal galvanic vestibular stimulation (sGVS), delivered at frequencies ranging from 0.08 to 2.0 Hz, induces vestibular illusions of side-to-side motion and robust modulation of muscle sympathetic nerve activity (MSNA) to the lower legs. We have previously documented, in seated subjects, de novo synthesis of bursts of MSNA that are temporally locked to the sinusoidal stimulus rather than to the cardiac-related rhythm. Here we tested the hypothesis that this vestibular entrainment of MSNA is higher in the upright than in the supine position. MSNA was recorded from the common peroneal nerve in 10 subjects lying on a tilt table. Bipolar binaural sGVS (+/-2 mA, 200 cycles) was applied to the mastoid processes at 0.2, 0.8, and 1.4 Hz in the supine and upright (75 degrees ) positions. In four subjects, "superentrainment" of MSNA occurred during sGVS, with strong bursts locked to one phase of the sinusoidal stimulus. This occurred more prominently in the upright position. On average, cross-correlation analysis revealed comparable vestibular modulation of MSNA in both positions at 0.2 Hz (84.9 +/- 3.6% and 78.7 +/- 5.7%), 0.8 Hz (77.4 +/- 3.9% and 74.4 +/- 8.9%), and 1.4 Hz (69.8 +/- 4.6% and 80.2 +/- 7.4%). However, in the supine position there was a significant linear fall in the magnitude of vestibular modulation with increasing frequency, whereas this was not present in the upright position. We conclude that vestibular contributions to the control of blood pressure are higher in the upright position. PMID- 27655964 TI - A switching cost for motor planning. AB - Movement planning consists of choosing the intended endpoint of the movement and selecting the motor program that will bring the effector on the endpoint. It is widely accepted that movement endpoint is updated on a trial-by-trial basis with respect to the observed errors and that the motor program for a given movement follows the rules of optimal feedback control. In this article, we show clear limitations of these theories. First, participants in the current study could not tune their motor program appropriately for each individual trial. This was true even when the participants selected the width of the target that they reached toward or when they had learned the appropriate motor program previously. These data are compatible with the existence of a switching cost for motor planning, which relates to the drop in performance due to an imposed switch of motor programs. This cost of switching shares many features of costs reported in cognitive task switching experiments and, when tested in the same participants, was correlated with it. Second, we found that randomly changing the width of a target over the course of a reaching experiment prevents the motor system from updating the endpoint of movements on the basis of the performance on the previous trial if the width of the target has changed. These results provide new insights into the process of motor planning and how it relates to optimal control theory and to an action selection based on the reward consequences of the motor program rather than that based on the observed error. PMID- 27655965 TI - Seeing pain and pleasure on self and others: behavioral and psychophysiological reactivity in immersive virtual reality. AB - Studies have explored behavioral and neural responses to the observation of pain in others. However, much less is known about how taking a physical perspective influences reactivity to the observation of others' pain and pleasure. To explore this issue we devised a novel paradigm in which 24 healthy participants immersed in a virtual reality scenario observed a virtual: needle penetrating (pain), caress (pleasure), or ball touching (neutral) the hand of an avatar seen from a first (1PP)- or a third (3PP)-person perspective. Subjective ratings and physiological responses [skin conductance responses (SCR) and heart rate (HR)] were collected in each trial. All participants reported strong feelings of ownership of the virtual hand only in 1PP. Subjective measures also showed that pain and pleasure were experienced as more salient than neutral. SCR analysis demonstrated higher reactivity in 1PP than in 3PP. Importantly, vicarious pain induced stronger responses with respect to the other conditions in both perspectives. HR analysis revealed equally lower activity during pain and pleasure with respect to neutral. SCR may reflect egocentric perspective, and HR may merely index general arousal. The results suggest that behavioral and physiological indexes of reactivity to seeing others' pain and pleasure were qualitatively similar in 1PP and 3PP. Our paradigm indicates that virtual reality can be used to study vicarious sensation of pain and pleasure without actually delivering any stimulus to participants' real body and to explore behavioral and physiological reactivity when they observe pain and pleasure from ego- and allocentric perspectives. PMID- 27655962 TI - Circuits for presaccadic visual remapping. AB - Saccadic eye movements rapidly displace the image of the world that is projected onto the retinas. In anticipation of each saccade, many neurons in the visual system shift their receptive fields. This presaccadic change in visual sensitivity, known as remapping, was first documented in the parietal cortex and has been studied in many other brain regions. Remapping requires information about upcoming saccades via corollary discharge. Analyses of neurons in a corollary discharge pathway that targets the frontal eye field (FEF) suggest that remapping may be assembled in the FEF's local microcircuitry. Complementary data from reversible inactivation, neural recording, and modeling studies provide evidence that remapping contributes to transsaccadic continuity of action and perception. Multiple forms of remapping have been reported in the FEF and other brain areas, however, and questions remain about the reasons for these differences. In this review of recent progress, we identify three hypotheses that may help to guide further investigations into the structure and function of circuits for remapping. PMID- 27655963 TI - alpha7-nAChR agonist enhances neural plasticity in the hippocampus via a GABAergic circuit. AB - Agonists of the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) have entered clinical trials as procognitive agents for treating schizophrenia and Alzheimer's disease. The most advanced compounds are orthosteric agonists, which occupy the ligand binding site. At the molecular level, agonist activation of alpha7-nAChR is reasonably well understood. However, the consequences of activating alpha7-nAChRs on neural circuits underlying cognition remain elusive. Here we report that an alpha7-nAChR agonist (FRM-17848) enhances long-term potentiation (LTP) in rat septo-hippocampal slices far below the cellular EC50 but at a concentration that coincides with multiple functional outcome measures as we reported in Stoiljkovic M, Leventhal L, Chen A, Chen T, Driscoll R, Flood D, Hodgdon H, Hurst R, Nagy D, Piser T, Tang C, Townsend M, Tu Z, Bertrand D, Koenig G, Hajos M. Biochem Pharmacol 97: 576-589, 2015. In this same concentration range, we observed a significant increase in spontaneous gamma aminobutyric acid (GABA) inhibitory postsynaptic currents and a moderate suppression of excitability in whole cell recordings from rat CA1 pyramidal neurons. This modulation of GABAergic activity is necessary for the LTP-enhancing effects of FRM-17848, since inhibiting GABAA alpha5-subunit-containing receptors fully reversed the effects of the alpha7-nAChR agonist. These data suggest that alpha7-nAChR agonists may increase synaptic plasticity in hippocampal slices, at least in part, through a circuit-level enhancement of a specific subtype of GABAergic receptor. PMID- 27655967 TI - Dissociable roles of preSMA in motor sequence chunking and hand switching-a TMS study. AB - Motor chunking, the grouping of individual movements into larger units, is crucial for sequential motor performance. The presupplementary motor area (preSMA) is involved in chunking and other related processes such as task switching, response selection, and response inhibition that are crucial for organizing sequential movements. However, previous studies have not systematically differentiated the role of preSMA in motor chunking and hand switching, thus leaving its relative contribution to each of these processes unclear. The aim of this study is to demonstrate the differential role of preSMA in motor chunking and hand switching. We designed motor sequences in which different kinds of hand switches (switching toward the right or left hand or continuing with the right hand) were counterbalanced across between- and within chunk sequence points. Eighteen healthy, right-handed participants practiced four short subsequences (chunks) of key presses. In a subsequent task, these chunks had to be concatenated into one long sequence. We applied double-pulse transcranial magnetic stimulation (TMS) over left preSMA or left M1 areas at sequence initiation, between chunks, or within chunks. TMS over the left preSMA significantly slowed the next response when stimulation was given between chunks, but only if a hand switch toward the contralateral (right) hand was required. PreSMA stimulation within chunks did not interfere with responses. TMS over the left M1 area delayed responses with the contralateral hand, both within and between chunks. Both preSMA and M1 stimulation decreased response times at sequence initiation. These results suggest that left preSMA is not necessary for chunking per se, but rather for organizing complex movements that require chunking and hand switching simultaneously. PMID- 27655966 TI - Physiology and anatomy of neurons in the medial superior olive of the mouse. AB - In mammals with good low-frequency hearing, the medial superior olive (MSO) computes sound location by comparing differences in the arrival time of a sound at each ear, called interaural time disparities (ITDs). Low-frequency sounds are not reflected by the head, and therefore level differences and spectral cues are minimal or absent, leaving ITDs as the only cue for sound localization. Although mammals with high-frequency hearing and small heads (e.g., bats, mice) barely experience ITDs, the MSO is still present in these animals. Yet, aside from studies in specialized bats, in which the MSO appears to serve functions other than ITD processing, it has not been studied in small mammals that do not hear low frequencies. Here we describe neurons in the mouse brain stem that share prominent anatomical, morphological, and physiological properties with the MSO in species known to use ITDs for sound localization. However, these neurons also deviate in some important aspects from the typical MSO, including a less refined arrangement of cell bodies, dendrites, and synaptic inputs. In vitro, the vast majority of neurons exhibited a single, onset action potential in response to suprathreshold depolarization. This spiking pattern is typical of MSO neurons in other species and is generated from a complement of Kv1, Kv3, and IH currents. In vivo, mouse MSO neurons show bilateral excitatory and inhibitory tuning as well as an improvement in temporal acuity of spiking during bilateral acoustic stimulation. The combination of classical MSO features like those observed in gerbils with more unique features similar to those observed in bats and opossums make the mouse MSO an interesting model for exploiting genetic tools to test hypotheses about the molecular mechanisms and evolution of ITD processing. PMID- 27655970 TI - Derivation, Replication, and Validity Analyses of a Screener for the Behavioral Assessment of Executive Functions in Young Adults. AB - Ecologically valid indicators of executive functions are designed to capture dysfunction not easily measured in a lab setting. Here, we present two studies on the development and validity analyses of a behavioral screener for executive functions among young adults. In Study 1, we derived a four-factor (problem solving, attentional control, behavioral control, and emotional control) behavioral screener using a sample of 765 individuals. We used invariance analyses to evaluate the screener's measurement reliability across sex. In Study 2, we replicated the screener derivation analyses using an independent sample of 197 undergraduates. To further examine the screener's validity, we evaluated it against a well-known executive functions rating scale. The four-factor model was supported in both samples and analyses provided support for this screener as a valid and reliable measure for everyday executive functions among young adults. PMID- 27655969 TI - Three-dimensional ocular kinematics underlying binocular single vision. AB - We have analyzed the binocular coordination of the eyes during far-to-near refixation saccades based on the evaluation of distance ratios and angular directions of the projected target images relative to the eyes' rotation centers. By defining the geometric point of binocular single vision, called Helmholtz point, we found that disparities during fixations of targets at near distances were limited in the subject's three-dimensional visual field to the vertical and forward directions. These disparities collapsed to simple vertical disparities in the projective binocular image plane. Subjects were able to perfectly fuse the vertically disparate target images with respect to the projected Helmholtz point of single binocular vision, independent of the particular location relative to the horizontal plane of regard. Target image fusion was achieved by binocular torsion combined with corrective modulations of the differential half-vergence angles of the eyes in the horizontal plane. Our findings support the notion that oculomotor control combines vergence in the horizontal plane of regard with active torsion in the frontal plane to achieve fusion of the dichoptic binocular target images. PMID- 27655968 TI - Edge orientation signals in tactile afferents of macaques. AB - The orientation of edges indented into the skin has been shown to be encoded in the responses of neurons in primary somatosensory cortex in a manner that draws remarkable analogies to their counterparts in primary visual cortex. According to the classical view, orientation tuning arises from the integration of untuned input from thalamic neurons with aligned but spatially displaced receptive fields (RFs). In a recent microneurography study with human subjects, the precise temporal structure of the responses of individual mechanoreceptive afferents to scanned edges was found to carry information about their orientation. This putative mechanism could in principle contribute to or complement the classical rate-based code for orientation. In the present study, we further examine orientation information carried by mechanoreceptive afferents of Rhesus monkeys. To this end, we record the activity evoked in cutaneous mechanoreceptive afferents when edges are indented into or scanned across the skin. First, we confirm that information about the edge orientation can be extracted from the temporal patterning in afferent responses of monkeys, as is the case in humans. Second, we find that while the coarse temporal profile of the response can be predicted linearly from the layout of the RF, the fine temporal profile cannot. Finally, we show that orientation signals in tactile afferents are often highly dependent on stimulus features other than orientation, which complicates putative decoding strategies. We discuss the challenges associated with establishing a neural code at the somatosensory periphery, where afferents are exquisitely sensitive and nearly deterministic. PMID- 27655971 TI - How Small Is Big: Sample Size and Skewness. AB - Sample sizes of 50 have been cited as sufficient to obtain stable means and standard deviations in normative test data. The influence of skewness on this minimum number, however, has not been evaluated. Normative test data with varying levels of skewness were compiled for 12 measures from 7 tests collected as part of ongoing normative studies in Brisbane, Australia. Means and standard deviations were computed from sample sizes of 10 to 100 drawn with replacement from larger samples of 272 to 973 cases. The minimum sample size was determined by the number at which both mean and standard deviation estimates remained within the 90% confidence intervals surrounding the population estimates. Sample sizes of greater than 85 were found to generate stable means and standard deviations regardless of the level of skewness, with smaller samples required in skewed distributions. A formula was derived to compute recommended sample size at differing levels of skewness. PMID- 27655977 TI - Stem Cell Therapy for Knee Pain-What Exactly Are We Injecting, and Why? PMID- 27655972 TI - Knockdown of Unconventional Myosin ID Expression Induced Morphological Change in Oligodendrocytes. AB - Myelin is a special multilamellar structure involved in various functions in the nervous system. In the central nervous system, the oligodendrocyte (OL) produces myelin and has a unique morphology. OLs have a dynamic membrane sorting system associated with cytoskeletal organization, which aids in the production of myelin. Recently, it was reported that the assembly and disassembly of actin filaments is crucial for myelination. However, the partner myosin molecule which associates with actin filaments during the myelination process has not yet been identified. One candidate myosin is unconventional myosin ID (Myo1d) which is distributed throughout central nervous system myelin; however, its function is still unclear. We report here that Myo1d is expressed during later stages of OL differentiation, together with myelin proteolipid protein (PLP). In addition, Myo1d is distributed at the leading edge of the myelin-like membrane in cultured OL, colocalizing mainly with actin filaments, 2',3'-cyclic nucleotide phosphodiesterase and partially with PLP. Myo1d-knockdown with specific siRNA induces significant morphological changes such as the retraction of processes and degeneration of myelin-like membrane, and finally apoptosis. Furthermore, loss of Myo1d by siRNA results in the impairment of intracellular PLP transport. Together, these results suggest that Myo1d may contribute to membrane dynamics either in wrapping or transporting of myelin membrane proteins during formation and maintenance of myelin. PMID- 27655978 TI - Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis. AB - BACKGROUND: Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported. METHODS: We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score. RESULTS: Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 +/- 16 (range, 32 to 82). CONCLUSIONS: The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655979 TI - Development and Validation of a Preoperative Surgical Site Infection Risk Score for Primary or Revision Knee and Hip Arthroplasty. AB - BACKGROUND: Surgical site infection (SSI) is a major complication following total joint arthroplasty. Host susceptibility to infection has emerged as an important predictor of SSI. The purpose of this study was to develop and validate a preoperative SSI risk-assessment tool for primary or revision knee and hip arthroplasty. METHODS: Data for 6,789 patients who underwent total joint arthroplasty (from the years 2000 to 2011) were obtained from a single hospital system. SSI was defined as a superficial infection within 30 days or deep infection within 1 year. Logistic regression modeling was utilized to create a risk scoring system for a derivation sample (n = 5,789; 199 SSIs), with validation performed on a hold-out sample (a subset of observations chosen randomly from the initial sample to form a testing set; n = 1,000; 41 SSIs). RESULTS: On the basis of logistic regression modeling, we created a scoring system to assess SSI risk (range, 0 to 35 points) that is the point sum of the following: primary hip arthroplasty (0 points); primary knee (1); revision hip (3); revision knee (3); non-insulin-dependent diabetes (1); insulin-dependent diabetes (1.5); chronic obstructive pulmonary disease (COPD) (1); inflammatory arthropathy (1.5); tobacco use (1.5); lower-extremity osteomyelitis or pyogenic arthritis (2); pelvis, thigh, or leg traumatic fracture (2); lower-extremity pathologic fracture (2.5); morbid obesity (2.5); primary bone cancer (4); reaction to prosthesis in the last 3 years (4); and history of staphylococcal septicemia (4.5). The risk score had good discriminatory capability (area under the ROC [receiver operating characteristic] curve = 0.77) and calibration (Hosmer Lemeshow chi-square test, p = 0.34) and was validated using the independent sample (area under the ROC curve = 0.72). A small subset of patients (5.9%) had a >10% estimated infection risk. CONCLUSIONS: The patient comorbidities composing the risk score heavily influenced SSI risk for primary or revision knee and hip arthroplasty. We believe that infection risk can be objectively determined in a preoperative setting with the proposed SSI risk score. PMID- 27655980 TI - Demographic, Clinical, and Operative Factors Affecting Long-Term Revision Rates After Cervical Spine Arthrodesis. AB - BACKGROUND: Limited data exist on long-term revision rates following cervical spine arthrodeses. The purposes of this study were to define reoperation rates after primary cervical arthrodeses and to identify risk factors for revisions. METHODS: New York State's all-payer health-care database was queried to identify all primary subaxial cervical arthrodeses occurring in the 16 years from 1997 through 2012. A total of 87,042 patients were included in the study cohort. Demographic information was extracted. Patients' preoperative medical comorbidities, surgical indications, and operative approaches were assembled using codes from the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification). The cohort was followed to revision surgical procedures, death, or the end of the study period. All subsequent contiguous spinal arthrodeses, including in the subaxial cervical spine, were considered revisions. The overall revision risk and the risk associated with various preoperative characteristics, surgical indications, and operative approaches were assessed using a Cox proportional hazard model. RESULTS: During the study period, 6,721 patients (7.7%) underwent revision. The median time to revision was 24.5 months. The probability of undergoing at least one revision by 192 months was 12.6%. Arthrodeses performed via anterior-only approaches had a significantly higher probability of revision (p < 0.001) at 13.4% (95% confidence interval [95% CI], 12.9% to 13.9%) than those performed via posterior approaches at 7.4% (95% CI, 6.6% to 8.4%) or circumferential (anterior and posterior) approaches at 5.2% (95% CI, 4.0% to 6.8%). This relationship persisted in multivariate analysis; compared with anterior surgical procedures, there was a significantly lower risk of revision (p < 0.001) for posterior surgical approaches at a hazard ratio of 0.76 (95% CI, 0.69 to 0.84) and circumferential approaches at a hazard ratio of 0.53 (95% CI, 0.42 to 0.66). Patient age of 18 to 34 years, white race, insurance status of Workers' Compensation or Medicare, and surgical procedures for spinal stenosis, spondylosis, deformity, and neoplasm were associated with elevated revision risk. Arthrodeses spanning few levels and those performed for fractures had a lower revision risk. CONCLUSIONS: Primary subaxial cervical spine arthrodeses had a probability of revision approaching 13% over a 16-year period, with elevated reoperation rates in patients undergoing anterior-only surgical procedures. Age, race, insurance status, surgical indication, and number of spinal levels included in the arthrodesis were also associated with reoperation risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655981 TI - Cellular and Morphological Alterations in the Vastus Lateralis Muscle as the Result of ACL Injury and Reconstruction. AB - BACKGROUND: Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation. METHODS: We performed diffusion tensor imaging magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine fiber type and size, Pax-7-positive (satellite) cells, and extracellular matrix (via wheat germ agglutinin straining). Using the diffusion tensor imaging data, the fiber tract length, pennation angle, and muscle volume were determined, yielding the physiological cross-sectional area (PCSA). Paired t tests were used to compare the effects of the injury between injured and uninjured limbs and the effects of surgery and rehabilitation within the injured limb. RESULTS: We found significant reductions before surgery in type-IIA muscle cross-sectional area (CSA; p = 0.03), extracellular matrix (p < 0.01), satellite cells per fiber (p < 0.01), pennation angle (p = 0.03), muscle volume (p = 0.02), and PCSA (p = 0.03) in the injured limb compared with the uninjured limb. Following surgery, these alterations in the injured limb persisted and the frequency of the IIA fiber type decreased significantly (p < 0.01) and that of the IIA/X hybrid fiber type increased significantly (p < 0.01). CONCLUSIONS: Significant and prolonged differences in muscle quality and morphology occurred after ACL injury and persisted despite reconstruction and extensive physical therapy. CLINICAL RELEVANCE: These results suggest the need to develop more effective early interventions following an ACL tear to prevent deleterious alterations within the quadriceps. PMID- 27655982 TI - Postoperative Limb-Offset Discrepancy Notably Affects Soft-Tissue Tension in Total Hip Arthroplasty. AB - BACKGROUND: Inadequate soft-tissue tension in total hip arthroplasty is regarded as one cause of dislocation or abductor muscle weakness. The purpose of the present study was to assess how the postoperative discrepancy in limb offset (consisting of both femoral offset and acetabular offset) affects soft-tissue tension compared with other factors among patients with unilateral hip disease undergoing total hip arthroplasty. METHODS: A total of 89 consecutive patients underwent mini-incision total hip arthroplasty involving an anterolateral or posterior approach and with use of a computer navigation system. Soft-tissue tension was measured by applying traction amounting to 40% of body weight with the joint positioned at 0 degrees , 15 degrees , 30 degrees , and 45 degrees of flexion. The separation between the cup and the prosthetic head was measured using the navigation system. RESULTS: The cup-head separation differed significantly for varying angles of flexion (p < 0.001), with the greatest distance noted at 15 degrees of flexion (mean and standard deviation, 11 +/- 5 mm). Stepwise multiple regression analysis showed that postoperative limb-offset discrepancy, an anterolateral approach, and preoperative abduction range of motion were correlated with the cup-head separation at 15 degrees of flexion. Postoperative limb-offset discrepancy was negatively correlated with the cup-head separation at 0 degrees , 15 degrees , and 30 degrees of flexion. CONCLUSIONS: Postoperative limb-offset discrepancy significantly affected the soft-tissue tension in total hip arthroplasty at varying degrees of flexion. This indicated that it is important to restore normal limb offset without overlengthening to obtain adequate soft-tissue tension in total hip arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655983 TI - Are We Prescribing Our Patients Too Much Pain Medication? Best Predictors of Narcotic Usage After Spinal Surgery for Scoliosis. AB - BACKGROUND: Physicians play a role in the current prescription drug-abuse epidemic. Surgeons often prescribe more postoperative narcotic pain medication than patients routinely need. Although narcotics are effective for severe, acute, postoperative pain, few evidence-based guidelines exist regarding the routinely required amount and duration of use post-hospital discharge. METHODS: Patients in a prospective cohort undergoing posterior spinal fusion for idiopathic scoliosis were asked preoperatively to rate their pain level, the level of pain expected each week postoperatively, and their pain tolerance. Post-discharge pain scores and narcotic use were reported at weekly intervals for 4 weeks postoperatively. Demographic data, preoperative Scoliosis Research Society (SRS)-22 scores, operative details, perioperative data, and self-reported pain levels were analyzed with respect to their association with total medication use and refills received. Disposal plans were also assessed. RESULTS: Seventy-two patients were enrolled, and 85% completed the surveys. The mean patient age was 14.9 years; 69% of the patients were female. The cohort was divided into 3 groups on the basis of total medication usage. The mean number of pills used in the middle (average-use) group was 49 pills. In postoperative week 4, narcotic usage was minimal (a mean of 2.9 pills by the highest-use group). Also by this time point, pain scores had, on average, returned to preoperative levels. Older age, male sex, a higher body mass index, and a higher preoperative pain score were associated with increased narcotic use. Sixty-seven percent of the patients planned to dispose of their unused medication, although only 59% of those patients planned on doing so in a manner recommended by the U.S. Food and Drug Administration. CONCLUSIONS: Postoperative narcotic dosing may be improved by considering patient age, weight, sex, and preoperative pain score. The precise estimation of individual narcotic needs is complex. Patient and family education on the importance and proper method of narcotic disposal is an essential component of minimizing the availability of unused postoperative medication. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655984 TI - Patient Compliance with Postoperative Lower-Extremity Non-Weight-Bearing Restrictions. AB - BACKGROUND: A period of non-weight-bearing is prescribed following many orthopaedic injuries and procedures. It is believed that a period of non-weight bearing is important for proper healing and recovery. The degree to which patients are compliant with non-weight-bearing instructions is unknown. The purpose of this study was to measure patient compliance with a period of prescribed non-weight-bearing. METHODS: In this single-blinded study, pressure sensitive film was embedded into short leg casts of 51 consecutive adult orthopaedic patients with unilateral lower-extremity abnormality who had been instructed to be strictly non-weight-bearing. Sensors were retrieved at the time of cast removal (mean, 24.3 days [range, 7 to 48 days]) and then were analyzed for force distribution and magnitude. Noncompliance was defined as maximum detectable pressure exerted on >=50% of the film. Patient characteristics and the time of year that the casts were worn were also examined to determine if they correlated with weight-bearing. RESULTS: Fourteen (27.5%) of 51 patients were noncompliant with the non-weight-bearing restriction. Six (42.9%) of the 14 noncompliant patients compared with 11 (29.7%) of the 37 compliant patients experienced an adverse event (p = 0.51). Sex, age, language spoken, body mass index, time in the cast, and the treating surgeon did not have a significant influence on weight-bearing performance (p > 0.05). Significantly greater weight bearing was found (p = 0.04) in warmer months (June to October) than in colder months (November to March) in the United States. CONCLUSIONS: The noncompliance rate with the postoperative non-weight-bearing restriction was 27.5% (95% confidence interval, 15.2% to 39.8%) in this patient group, despite explicit instructions and education about possible complications associated with weight bearing. The only factor found to have a significant effect on weight-bearing compliance was the time of year that the cast was worn. No significant difference was found between the complication rate of the compliant patients and that of the noncompliant patients. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655985 TI - Return to Work and Sport Following High Tibial Osteotomy: A Systematic Review. AB - BACKGROUND: The purpose of this study was to examine (1) timelines for return to sport and work following high tibial osteotomy (HTO), and (2) whether patients return to sport and work at levels similar to preoperative levels. METHODS: A systematic search was conducted across 3 databases (MEDLINE, Embase, and PubMed). Two reviewers independently screened the results for relevant articles. Data regarding patient demographics, indications, surgical technique, return to work and sport, and complication and failure rates were abstracted from eligible studies. RESULTS: Nineteen studies were included, involving 1,189 patients (64% male, 21% female, 15% unspecified) and 1,224 knees. Mean age was 46.2 years (range, 16 to 80 years). Opening-wedge HTO was most commonly used, followed by closing-wedge HTO and hemicallotasis. Mean follow-up was 65.4 months (range, 8 to 253 months). Overall, 87.2% of patients returned to sport postoperatively, and 78.6% returned at an equal or greater level. Among competitive athletes, 54% returned to competition. Overall, 84.5% of patients returned to work postoperatively, and 65.5% returned at an equal or greater level. Approximately 90% of patients who returned to work or sport did so within 1 year. The complication rate was 5.8%, with infection being the most common complication; 7.0% of patients progressed to a total knee arthroplasty at a mean of 6.7 years (range, 0.8 to 15 years) following HTO. CONCLUSIONS: The majority of patients undergoing HTO return to sport and work, and most return within 1 year of the operation. Most patients return to sport at a level equal to or greater than the preoperative level. Approximately two-thirds of patients return to an equal or greater level of physical work. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655987 TI - What's New in Hip Replacement. PMID- 27655986 TI - The Effects of Acupuncture on Chronic Knee Pain Due to Osteoarthritis: A Meta Analysis. AB - BACKGROUND: Acupuncture reportedly relieves chronic knee pain and improves physical function in patients diagnosed with osteoarthritis, but the duration of these effects is controversial. The aim of this study was to evaluate the temporal effects of acupuncture on chronic knee pain due to knee osteoarthritis by means of a meta-analysis. METHODS: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published through March 2015. Ten randomized controlled trials of acupuncture compared with sham acupuncture, usual care, or no intervention for chronic knee pain in patients with clinically diagnosed or radiographically confirmed knee osteoarthritis were included. All of the studies were available in English. Weighted mean differences (WMDs), 95% confidence intervals (CIs), publication bias, and heterogeneity were calculated. RESULTS: The acupuncture groups showed superior pain improvement (p < 0.001; WMD = -1.24 [95% CI, -1.92 to -0.56]; I(2) > 50%) and physical function (p < 0.001; WMD = 4.61 [95% CI, 2.24 to 6.97]; I(2) > 50%) in the short term (up to 13 weeks). The acupuncture groups showed superior physical function (p = 0.016; WMD = 2.73 [95% CI, 0.51 to 4.94]; I(2) > 50%) but not superior pain improvement (p = 0.199; WMD = -0.55 [95% CI, -1.39 to 0.29]; I(2) > 50%) in the long term (up to 26 weeks). Subgroup analysis revealed that the acupuncture groups tended to have better outcomes compared with the controls. Significant publication bias was not detected (p > 0.05), but the heterogeneity of the studies was substantial. CONCLUSIONS: This meta-analysis demonstrates that acupuncture can improve short and long-term physical function, but it appears to provide only short-term pain relief in patients with chronic knee pain due to osteoarthritis. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 27655988 TI - The Science of Health-Care Delivery. AB - As the health-care system evolves toward delivering greater value for the patient, orthopaedic surgeons are continually being challenged to manage the health of a population. The traditional focus of scientific inquiry within orthopaedics has been at the individual patient level. The science of health-care delivery is an evolving field that is aimed at bringing rigorous inquiry into determining the proper organizational design that can deliver high-quality and low-cost care for a population. This article provides an overview of basic concepts involved in systems and organizational theory relevant to orthopaedic surgery. PMID- 27655989 TI - Distribution of High-Volume Shoulder Arthroplasty Surgeons in the United States: Data from the 2014 Medicare Provider Utilization and Payment Data Release. AB - BACKGROUND: Access to total shoulder arthroplasty (TSA) may become a concern in the United States because of an aging and active population resulting in increased demand. As high-volume TSA surgeons have demonstrated superior outcomes, access to these surgeons is a matter of patient and public health policy interest. The release of the 2012 Medicare Provider Utilization and Payment Data Public Use File (MPUPD-PUF) in 2014 provided volume and reimbursement data for procedures performed by individual physicians participating in Medicare. This study analyzed surgeon prevalence, surgeon distribution, and factors associated with higher or lower surgeon prevalence in metropolitan areas. METHODS: The MPUPD-PUF was reviewed for the 2012 calendar year, and data were extracted for all physicians who performed a minimum of 11 TSA procedures for Medicare beneficiaries. Physicians in each major metropolitan area (population of >1 million) were grouped together. Average reimbursement, number of high-volume TSA surgeons, and number of total procedures were calculated per major metropolitan area. The presence of an American Shoulder and Elbow Surgeons (ASES) fellowship program and mean geographic reimbursement were analyzed for association with the number of high-volume TSA surgeons. RESULTS: The MPUPD-PUF included 774 surgeons across the United States who performed an annual minimum of 11 TSA procedures covered by Medicare, with a combined total of 19,505 TSA procedures. Of these surgeons, 45% practiced within major metropolitan areas with a population of >1 million. Surgeons who had completed an ASES fellowship had a higher volume of procedural claims (median, 26; range, 11 to 120) compared with other surgeons (median, 17; range, 11 to 163; p < 0.001). The distribution among major metropolitan areas was highly unequal, and more surgeons were present in cities with an ASES fellowship program. CONCLUSIONS: Access to high-volume shoulder arthroplasty surgeons by the Medicare population is lacking in multiple major metropolitan areas in the United States because of the uneven distribution of these surgeons. The method of analysis in this study allows for opportunities to target training programs as well as placement of physicians to ensure access to high-volume shoulder arthroplasty surgeons. PMID- 27655990 TI - Surgical Site Infection: Can We Predict the Future? Commentary on an article by Joshua S. Everhart, MD, MPH, et al.: "Development and Validation of a Preoperative Surgical Site Infection Risk Score for Primary or Revision Knee and Hip Arthroplasty". PMID- 27655991 TI - What Happened to My Quad? Commentary on an article by Brian Noehren, PT, PhD, et al.: "Cellular and Morphological Alterations in the Vastus Lateralis Muscle as the Result of ACL Injury and Reconstruction". PMID- 27655992 TI - Consider the Patient When Prescribing Total Non-Weight-Bearing: Commentary on an article by Christopher P. Chiodo, MD, et al.: "Patient Compliance with Postoperative Lower-Extremity Non-Weight-Bearing Restrictions". PMID- 27655993 TI - Effects of Music Intervention on State Anxiety and Physiological Indices in Patients Undergoing Mechanical Ventilation in the Intensive Care Unit. AB - Patients in intensive care units (ICUs) often experience stress and anxiety. Although stress and anxiety can be pharmacologically attenuated, some drugs cause adverse side effects such as bradycardia, immobility, and delirium. There is thus a need for an alternative treatment with no substantial adverse effects. Music intervention is a potential alternative. In the present study, we used cortisol levels, subjective questionnaires, and physiological parameters to explore the anxiety-reducing effects of music intervention in a sample of ICU patients on mechanical ventilation. Patients admitted to the ICU for >= 24 hr were randomly assigned to the music intervention ( n = 41) or control group ( n = 44). Music group patients individually listened to music from 4:00 to 4:30 p.m.; control group patients wore headphones but heard no music for the same 30 min. Anxiety was measured using serum cortisol levels, the Chinese Version of the State-Trait Anxiety Inventory, the Visual Analogue Scale for Anxiety, heart rate, and blood pressure. After adjusting for demographics, analysis of covariance showed that the music group had significantly better scores for all posttest measures ( p < .02) and pre-post differences ( p < .03) except for diastolic blood pressure. Because of music intervention's low cost and easy administration, clinical nurses may want to use music to reduce stress and anxiety for ICU patients. A single 30 min session might work immediately without any adverse effects. However, the duration of the effect is unclear; thus, each patient's mood should be monitored after the music intervention. PMID- 27655994 TI - Targeted autopsy practice for coroners is likely to miss diagnoses. PMID- 27655995 TI - Evidence for Human Adaptation and Foodborne Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus. AB - We investigated the evolution and epidemiology of a novel livestock-associated methicillin-resistant Staphylococcus aureus strain, which colonizes and infects urban-dwelling Danes even without a Danish animal reservoir. Genetic evidence suggests both poultry and human adaptation, with poultry meat implicated as a probable source. PMID- 27655997 TI - Bridge Therapy Outcomes in Patients With Mechanical Heart Valves. AB - BACKGROUND: Bridge therapy is associated with an increased risk of major bleeding in patients with atrial fibrillation and venous thromboembolism (TE) without a corresponding reduction in TE. The benefits of bridge therapy in patients with mechanical heart valve (MHV) prostheses interrupting warfarin for invasive procedures are not well described. METHODS AND RESULTS: A retrospective cohort study was conducted at an integrated health-care delivery system. Anticoagulated patients with MHV interrupting warfarin for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified. Patients were categorized according to exposure to bridge therapy during the periprocedural period and TE risk (low, medium, and high). Outcomes validated via manual chart review included clinically relevant bleeding, TE, and all-cause mortality in the 30 days following the procedure. There were 547 procedures in 355 patients meeting inclusion criteria. Mean cohort age was 65.2 years, and 38% were female. Bridge therapy was utilized in 466 (85.2%) procedures (95.2%, 77.3%, and 65.8% of high, medium, and low TE risk category procedures, respectively). The 30-day rate of clinically relevant bleeding was numerically higher in bridged (5.8%; 95% confidence interval [CI], 3.9%-8.3%) versus not bridged procedures (1.2%; 95% CI, <0.1%-6.7%; P = .102). No TEs or deaths were identified. CONCLUSION: The use of bridge therapy is common among patients with MHV and may be associated with increased bleeding risk. Further research is needed to determine whether bridge therapy reduces TE in patients with MHV interrupting warfarin for invasive procedures. PMID- 27655996 TI - Substantial Decline in Vaccine-Type Human Papillomavirus (HPV) Among Vaccinated Young Women During the First 8 Years After HPV Vaccine Introduction in a Community. AB - BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness and herd protection are not well established in community settings. Our objective was to determine trends in vaccine-type HPV in young women during the 8 years after vaccine introduction, to assess changes in HPV prevalence and characterize herd protection in a community. METHODS: We recruited 3 samples of sexually experienced, 13-26-year-old adolescent girls and young women (hereafter women; N = 1180) from 2006-2014: before widespread vaccine introduction (wave 1) and 3 (wave 2) and 7 (wave 3) years after vaccine introduction. We determined the prevalence of vaccine-type HPV (HPV-6, -11, -16, and -18) among all, vaccinated, and unvaccinated women at waves 1, 2, and 3, adjusted for differences in participant characteristics, then examined whether changes in HPV prevalence were significant using inverse propensity score-weighted logistic regression. RESULTS: Vaccination rates increased from 0% to 71.3% across the 3 waves. Adjusted vaccine-type HPV prevalence changed from 34.8% to 8.7% (75.0% decline) in all women, from 34.9% to 3.2% (90.8% decline) in vaccinated women, and from 32.5% to 22.0% (32.3% decline) in unvaccinated women. Among vaccinated participants, vaccine-type HPV prevalence decreased significantly from wave 1 to wave 2 (adjusted odds ratio, 0.21; 95% confidence interval, .13-.34) and from wave 1 to wave 3 (0.06; .03-.13). The same decreases were also significant among unvaccinated participants (adjusted odds ratios, 0.44; [95% confidence interval, .27-.71] and 0.59; [.35-.98], respectively). CONCLUSIONS: The prevalence of vaccine-type HPV decreased >90% in vaccinated women, demonstrating high effectiveness in a community setting, and >30% in unvaccinated women, providing evidence of herd protection. PMID- 27655998 TI - Prevalence and Risk Factors Associated With Hypertension in von Willebrand Disease. AB - BACKGROUND: von Willebrand factor (VWF) is a biomarker for endothelial damage. Increased VWF levels are observed in hypertension (HTN) and disorders of endothelial dysfunction, for example, atherosclerotic heart disease (ASHD) and diabetes. Whether low VWF protects against HTN is unknown. METHODS: To determine prevalence and risk factors for HTN in patients with von Willebrand disease (VWD), we conducted a cross-sectional analysis of discharge data from the National Inpatient Sample, 2009 to 2011. Group comparisons were performed by Rao Scott chi2 test. Odds of HTN and HTN outcomes in VWD were estimated by weighted multivariable logistic regression. RESULTS: The prevalence of hypertension in patients with VWD (N = 7556), 37.35%, was significantly lower than that in non VWD patients (N = 19 918 970), 49.40%, P < .0001. Hypertension risk factors (hyperlipidemia, diabetes, smoking, hepatitis C, and HIV) and HTN outcomes (ASHD, myocardial infarction [MI], ischemic stroke, and renal failure) were less common in patients with VWD than in non-VWD patients, all P <= .0001. Patients with VWD were younger, 49.67 versus 57.30 years, Caucasian, 82.23% versus 68.35%, and female, 75.44% versus 59.61%, P < .0001. Patients with HTN were older, 67.55 versus 47.29 years, male, 45.99% versus 34.90%, and had more HTN risk factors and HTN outcomes than those without HTN, all P < .0001, including male and female subgroups, each P < .0001. The unadjusted odds of HTN in patients with VWD (odds ratio [OR] = 0.611, P < .0001) and of HTN outcomes in patients with VWD (ASHD, OR = 0.509; MI, OR = 0.422; ischemic stroke, OR = 0.521; renal failure, OR = 0.420, all P < .0001) became insignificant after adjustment for HTN risk factors plus demographics (age/race/gender), OR = 1.035, P = .260. CONCLUSION: The risk of HTN is reduced in patients with VWD, but not after adjustment for HTN risk factors plus demographics, as patients with VWD not having HTN are also typically young, Caucasian, and female. PMID- 27655999 TI - Evolution of Cognitive Function After Transcatheter Aortic Valve Implantation. AB - BACKGROUND: This study aimed to assess the evolution of cognitive function after transcatheter aortic valve implantation (TAVI). Previous smaller studies reported conflicting results on the evolution of cognitive function after TAVI. METHODS AND RESULTS: In this prospective cohort, cognitive function was measured in 229 patients >=70 years using the Mini Mental State Examination before and 6 months after TAVI. Cognitive deterioration or improvement was defined as change of >=3 points decrease or increase in the Mini Mental State Examination score between baseline and follow-up. Cognitive deterioration was found in 29 patients (12.7%). Predictive analysis using logistic regression did not identify any statistically significant predictor of cognitive deterioration. A review of individual medical records in 8 patients with a major Mini Mental State Examination score decrease of >=5 points revealed specific causes in 6 cases (postinterventional delirium in 2; postinterventional stroke, progressive renal failure, progressive heart failure, or combination of preexisting cerebrovascular disease and mild cognitive impairment in 1 each). Among 48 patients with impaired baseline cognition (Mini Mental State Examination score <26 points), 18 patients (37.5%) cognitively improved. The preinterventional aortic valve area was lower in patients who cognitively improved (median aortic valve area 0.60 cm2) as compared with patients who did not improve (median aortic valve area 0.70 cm2; P=0.01). CONCLUSIONS: This is the first study providing evidence that TAVI results in cognitive improvement among patients who had impaired preprocedural cognitive function, possibly related to hemodynamic improvement in patients with severe aortic stenosis. Our results confirm that some patients experience cognitive deterioration after TAVI. PMID- 27656000 TI - Changes in Left Ventricular Ejection Fraction Predict Survival and Hospitalization in Heart Failure With Reduced Ejection Fraction. AB - BACKGROUND: Left ventricular remodeling, as commonly measured by left ventricular ejection fraction (LVEF), is associated with clinical outcomes. Although change in LVEF over time should reflect response to therapy and clinical course, serial measurement of LVEF is inconsistently performed in observational settings, and the incremental prognostic value of change in LVEF has not been well characterized. METHODS AND RESULTS: The beta-Blocker Evaluation of Survival Trial measured LVEF by radionuclide ventriculography at baseline and at 3 and 12 months after randomization. We built a series of multivariable models with 16 clinical parameters plus change in LVEF for predicting 4 major clinical end points, including the trial's primary end point of all-cause mortality. Among 2484 patients with at least 1 follow-up LVEF, change in LVEF was the second most significant predictor (behind baseline creatinine) of all-cause mortality (adjusted hazard ratio for improvement in LVEF by >=5 U responder versus nonresponder [95% confidence intervals] for all-cause mortality=0.62 [0.52 0.73]). Other end points, including heart failure hospitalization or the composite of all-cause mortality and heart failure hospitalization, yielded similar results. LVEF change >=5 U was associated with a modest increase in discrimination when added to traditional predictors and was predictive of outcomes in both the bucindolol and placebo treatment groups. LVEF change as a predictor of outcomes was affected by sex and race, with evidence that LVEF improvement is associated with less survival benefit in African Americans and women. CONCLUSIONS: Serial evaluation for LVEF change predicts both survival and heart failure hospitalization and provides a dynamic/real-time measure of prognosis in heart failure with reduced LVEF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000560. PMID- 27656001 TI - World War II Mobilization in Men's Work Lives: Continuity or Disruption for the Middle Class? AB - The labor needs of World War II fueled a growing demand for both military and war industry personnel. This longitudinal study investigates mobilization into these competing activities and their work life effects among men from the middle class. Hazard estimates show significant differences in wartime activities across occupations, apart from other deferment criteria. By war's end, critical employment, in contrast to military service, is positively associated with supervisory responsibility for younger men and with occupation change. This empoloyment does not predict postwar career advancement up to the 1970s. By comparison, men who were officers had a "pipeline" to advancement after the war, whereas other service men fared worse than nonveterans. PMID- 27656002 TI - Colored dissolved organic matter dynamics and anthropogenic influences in a major transboundary river and its coastal wetland. AB - Most transboundary rivers and their wetlands are subject to considerable anthropogenic pressures associated with multiple and often conflicting uses. In the Eastern Mediterranean such systems are also particularly vulnerable to climate change, posing additional challenges for integrated water resources management. Comprehensive measurements of the optical signature of colored dissolved organic matter (CDOM) were combined with measurements of river discharges and water physicochemical and biogeochemical properties, to assess carbon dynamics, water quality, and anthropogenic influences in a major transboundary system of the Eastern Mediterranean, the Evros (or, Maritsa or, Meric) river and its Ramsar protected coastal wetland. Measurements were performed over three years, in seasons characterized by different hydrologic conditions and along transects extending more than 70 km from the freshwater end member to two kilometers offshore in the Aegean Sea. Changes in precipitation, anthropogenic dissolved organic matter (DOM) inputs from the polluted Ergene tributary, and the irregular operation of a dam were key factors driving water quality, salinity regimes, and biogeochemical properties in the Evros delta and coastal waters. Marsh outwelling affected coastal carbon quality, but the influence of wetlands was often masked by anthropogenic DOM contributions. A distinctive five-peak CDOM fluorescence signature was characteristic of upstream anthropogenic inputs and clearly tracked the influence of freshwater discharges on water quality. Monitoring of this CDOM fluorescence footprint could have direct applications to programs focusing on water quality and environmental assessment in this and other transboundary rivers where management of water resources remains largely ineffective. PMID- 27656003 TI - Distribution of mesopredatory fish determined by habitat variables in a predator depleted coastal system. AB - Shallow nearshore habitats are highly valued for supporting marine ecosystems, but are subject to intense human-induced pressures. Mesopredatory fish are key components in coastal food webs, and alterations in their abundance may have evident effects also on other parts of the ecosystem. The aim of this study was to clarify the relationship between the abundance of coastal mesopredatory fish, defined as mid-trophic level demersal and benthic species with a diet consisting predominantly of invertebrates, and ambient environmental variables in a fjord system influenced by both eutrophication and overfishing. A field survey was conducted over a coastal gradient comprising 300 data points sampled consistently for fish community and environmental data. Results from multivariate and univariate analyses supported each other, demonstrating that mesopredatory fish abundance at species and functional group level was positively related to the cover of structurally complex vegetation and negatively related to eutrophication, as measured by water transparency. Contrary to other studies showing an inverse relationship to piscivore abundance over time, the spatial distribution of mesopredatory fish was not locally regulated by the abundance of piscivorous fish, probably attributed to piscivores being at historically low levels due to previous overfishing. Mesopredatory fish abundance was highest in areas with high habitat quality and positively related to the abundance of piscivores, suggesting a predominance of bottom-up processes. We conclude that, in parallel with ongoing regulations of fishing pressure, measures to restore habitat function and food web productivity are important for the recovery of coastal fish communities in the area. PMID- 27656004 TI - Quantification of Stereochemical Communication in Metal-Organic Assemblies. AB - The derivation and application of a statistical mechanical model to quantify stereochemical communication in metal-organic assemblies is reported. The factors affecting the stereochemical communication within and between the metal stereocenters of the assemblies were experimentally studied by optical spectroscopy and analyzed in terms of a free energy penalty per "incorrect" amine enantiomer incorporated, and a free energy of coupling between stereocenters. These intra- and inter-vertex coupling constants are used to track the degree of stereochemical communication across a range of metal-organic assemblies (employing different ligands, peripheral amines, and metals); temperature dependent equilibria between diastereomeric cages are also quantified. The model thus provides a unified understanding of the factors that shape the chirotopic void spaces enclosed by metal-organic container molecules. PMID- 27656007 TI - Formation of ridges in a stable lithosphere in mantle convection models with a viscoplastic rheology. AB - Numerical simulations of mantle convection with a viscoplastic rheology usually display mobile, episodic or stagnant lid regimes. In this study, we report a new convective regime in which a ridge can form without destabilizing the surrounding lithosphere or forming subduction zones. Using simulations in 2-D spherical annulus geometry, we show that a depth-dependent yield stress is sufficient to reach this ridge only regime. This regime occurs when the friction coefficient is close to the critical value between mobile lid and stagnant lid regimes. Maps of convective regime as a function of the parameters friction coefficients and depth dependence of viscosity are provided for both basal heating and mixed heating situations. The ridge only regime appears for both pure basal heating and mixed heating mode. For basal heating, this regime can occur for all vertical viscosity contrasts, while for mixed heating, a highly viscous deep mantle is required. PMID- 27656006 TI - Spectral properties of Titan's impact craters imply chemical weathering of its surface. AB - We examined the spectral properties of a selection of Titan's impact craters that represent a range of degradation states. The most degraded craters have rims and ejecta blankets with spectral characteristics that suggest that they are more enriched in water ice than the rims and ejecta blankets of the freshest craters on Titan. The progression is consistent with the chemical weathering of Titan's surface. We propose an evolutionary sequence such that Titan's craters expose an intimate mixture of water ice and organic materials, and chemical weathering by methane rainfall removes the soluble organic materials, leaving the insoluble organics and water ice behind. These observations support the idea that fluvial processes are active in Titan's equatorial regions. PMID- 27656005 TI - Mercury in Marine and Oceanic Waters-a Review. AB - Mercury contamination in water has been an issue to the environment and human health. In this article, mercury in marine and oceanic waters has been reviewed. In the aquatic environment, mercury occurs in many forms, which depend on the oxidation-reduction conditions. These forms have been briefly described in this article. Mercury concentrations in marine waters in the different parts of the world have been presented. In the relevant literature, two models describing the fate and behavior of mercury in saltwater reservoirs have been presented, a conceptual model which treats all the oceans as one ocean and the "ocean margin" model, providing that the ocean margins manifested themselves as the convergence of continents and oceans, covering such geological features, such as estuaries, inland seas, and the continental shelf. These two conceptual models have been summarized in the text. The mercury content in benthic sediments usually reflects is level in the water reservoir, particularly in reservoirs situated in contaminated areas (mines, metallurgical plants, chemically protected crops). The concentrations of mercury and its compounds determined in the sediments in surface waters in the different parts of the world have been presented. Due to the fact that the pollution caused by mercury is a serious threat for the marine environment, the short paragraph about mercury bioaccumulation in aquatic organisms has been included. The cited data demonstrated a large scatter of mercury contents both between the fish species and the water areas. Mathematical models, valuable tools which provide information about the possible responses of ecosystems, developed to simulate mercury emissions, both at a small scale, for local water reservoirs, and at a global scale, as well as to model mercury bioaccumulation in the chain web of aquatic systems have been described. PMID- 27656008 TI - Charge exchange in cometary coma: Discovery of H- ions in the solar wind close to comet 67P/Churyumov-Gerasimenko. AB - As Rosetta was orbiting comet 67P/Churyumov-Gerasimenko, the Ion and Electron Sensor detected negative particles with angular distributions like those of the concurrently measured solar wind protons but with fluxes of only about 10% of the proton fluxes and energies of about 90% of the proton energies. Using well-known cross sections and energy-loss data, it is determined that the fluxes and energies of the negative particles are consistent with the production of H- ions in the solar wind by double charge exchange with molecules in the coma. PMID- 27656010 TI - Accelerated deforestation in the humid tropics from the 1990s to the 2000s. AB - Using a consistent, 20 year series of high- (30 m) resolution, satellite-based maps of forest cover, we estimate forest area and its changes from 1990 to 2010 in 34 tropical countries that account for the majority of the global area of humid tropical forests. Our estimates indicate a 62% acceleration in net deforestation in the humid tropics from the 1990s to the 2000s, contradicting a 25% reduction reported by the United Nations Food and Agriculture Organization Forest Resource Assessment. Net loss of forest cover peaked from 2000 to 2005. Gross gains accelerated slowly and uniformly between 1990-2000, 2000-2005, and 2005-2010. However, the gains were overwhelmed by gross losses, which peaked from 2000 to 2005 and decelerated afterward. The acceleration of humid tropical deforestation we report contradicts the assertion that losses decelerated from the 1990s to the 2000s. PMID- 27656009 TI - Near-Earth injection of MeV electrons associated with intense dipolarization electric fields: Van Allen Probes observations. AB - Substorms generally inject tens to hundreds of keV electrons, but intense substorm electric fields have been shown to inject MeV electrons as well. An intriguing question is whether such MeVelectron injections can populate the outer radiation belt. Here we present observations of a substorm injection of MeV electrons into the inner magnetosphere. In the premidnight sector at L ~ 5.5, Van Allen Probes (Radiation Belt Storm Probes)-A observed a large dipolarization electric field (50 mV/m) over ~40 s and a dispersionless injection of electrons up to ~3 MeV. Pitch angle observations indicated betatron acceleration of MeV electrons at the dipolarization front. Corresponding signals of MeV electron injection were observed at LANL-GEO, THEMIS-D, and GOES at geosynchronous altitude. Through a series of dipolarizations, the injections increased the MeV electron phase space density by 1 order of magnitude in less than 3 h in the outer radiation belt (L > 4.8). Our observations provide evidence that deep injections can supply significant MeV electrons. PMID- 27656012 TI - Children's Sex and the Happiness of Parents. AB - Demographers are interested in sex preferences for children because they can skew sex ratios and influence population-level fertility, parenting behavior, and family outcomes. Based on parity progression ratios, in most European countries, there are no sex preferences for a first child, but a strong preference for mixed sex children. We hypothesize that mixed-sex preferences also influence parental happiness. Parents' disappointment with a second child of the same sex as the first could have negative effects for parents and children. We use longitudinal data from the German Socio-Economic Panel and the British Household Panel Study to examine parental happiness by the children's sex and analyze whether these effects differ by parent's sex, age, nativity, and educational attainment. The results are only partially consistent with predictions from parity progression ratios. As expected, parental happiness does not depend on the sex of the first child. We find weak evidence suggesting that two boys decrease happiness, but the findings are not consistent across German and British data or across subpopulations. Moreover, two girls do not reduce happiness. Although sex preferences influence fertility, they appear to have little impact on happiness, perhaps because of unobserved positive factors associated with having same-sex children. PMID- 27656011 TI - Parenthood and Well-Being: The Moderating Role of Leisure and Paid Work. AB - This study contributes to our knowledge on the association between parenthood and psychological well-being by examining whether pre-parenthood lifestyles (leisure and paid work) moderate the transition to parenthood. We expected that people with less active lifestyles would find it easier to adapt to the demands of parenthood. Using eleven waves of the Swiss Household Panel (N = 1332 men and 1272 women; 1999-2008, 2010), fixed effects models are estimated for men and women separately. Results show that-on average-parenthood was not associated with well-being for men, whereas it increased well-being for women. As expected, the well-being premium/cost to parenthood was contingent upon individuals' lifestyle before the transition to parenthood. For men, parenthood reduced well-being, but only if they frequently participated in leisure before the birth of the child. For women, motherhood had a beneficial effect on well-being but this effect was weaker for women who combined leisure with working long hours before motherhood. PMID- 27656013 TI - Interpretation and application of carbon isotope ratios in freshwater diatom silica. AB - Carbon incorporated into diatom frustule walls is protected from degradation enabling analysis for carbon isotope composition (delta13Cdiatom). This presents potential for tracing carbon cycles via a single photosynthetic host with well constrained ecophysiology. Improved understanding of environmental processes controlling carbon delivery and assimilation is essential to interpret changes in freshwater delta13Cdiatom. Here relationships between water chemistry and delta13Cdiatom from contemporary regional data sets are investigated. Modern diatom and water samples were collected from river catchments within England and lake sediments from across Europe. The data suggest dissolved, biogenically produced carbon supplied proportionately to catchment productivity was critical in the rivers and soft water lakes. However, dissolved carbon from calcareous geology overwhelmed the carbon signature in hard water catchments. Both results demonstrate carbon source characteristics were the most important control on delta13Cdiatom, with a greater impact than productivity. Application of these principles was made to a sediment record from Lake Tanganyika. delta13Cdiatom co varied with delta13Cbulk through the last glacial and Holocene. This suggests carbon supply was again dominant and exceeded authigenic demand. This first systematic evaluation of contemporary delta13Cdiatom controls demonstrates that diatoms have the potential to supply a record of carbon cycling through lake catchments from sediment records over millennial timescales. PMID- 27656014 TI - Monocyte-Derived Macrophages Modulate Inflammation and Promote Long-Term Functional Recovery in a Mouse Model of Ischemia. PMID- 27656015 TI - A Schwanncentric View of Axon Arborization in Neuromuscular Junction (NMJ) Formation. PMID- 27656016 TI - Heteromodal Cortical Areas Encode Sensory-Motor Features of Word Meaning. AB - The capacity to process information in conceptual form is a fundamental aspect of human cognition, yet little is known about how this type of information is encoded in the brain. Although the role of sensory and motor cortical areas has been a focus of recent debate, neuroimaging studies of concept representation consistently implicate a network of heteromodal areas that seem to support concept retrieval in general rather than knowledge related to any particular sensory-motor content. We used predictive machine learning on fMRI data to investigate the hypothesis that cortical areas in this "general semantic network" (GSN) encode multimodal information derived from basic sensory-motor processes, possibly functioning as convergence-divergence zones for distributed concept representation. An encoding model based on five conceptual attributes directly related to sensory-motor experience (sound, color, shape, manipulability, and visual motion) was used to predict brain activation patterns associated with individual lexical concepts in a semantic decision task. When the analysis was restricted to voxels in the GSN, the model was able to identify the activation patterns corresponding to individual concrete concepts significantly above chance. In contrast, a model based on five perceptual attributes of the word form performed at chance level. This pattern was reversed when the analysis was restricted to areas involved in the perceptual analysis of written word forms. These results indicate that heteromodal areas involved in semantic processing encode information about the relative importance of different sensory-motor attributes of concepts, possibly by storing particular combinations of sensory and motor features. SIGNIFICANCE STATEMENT: The present study used a predictive encoding model of word semantics to decode conceptual information from neural activity in heteromodal cortical areas. The model is based on five sensory-motor attributes of word meaning (color, shape, sound, visual motion, and manipulability) and encodes the relative importance of each attribute to the meaning of a word. This is the first demonstration that heteromodal areas involved in semantic processing can discriminate between different concepts based on sensory-motor information alone. This finding indicates that the brain represents concepts as multimodal combinations of sensory and motor representations. PMID- 27656018 TI - Involvement of Spinal IL-6 Trans-Signaling in the Induction of Hyperexcitability of Deep Dorsal Horn Neurons by Spinal Tumor Necrosis Factor-Alpha. AB - During peripheral inflammation, both spinal TNF-alpha and IL-6 are released within the spinal cord and support the generation of inflammation-evoked spinal hyperexcitability. However, whether spinal TNF-alpha and IL-6 act independently in parallel or in a functionally dependent manner has not been investigated. In extracellular recordings from mechanonociceptive deep dorsal horn neurons of normal rats in vivo, we found that spinal application of TNF-alpha increased spinal neuronal responses to mechanical stimulation of knee and ankle joints. This effect was significantly attenuated by either sgp130, which blocks IL-6 trans-signaling mediated by IL-6 and its soluble receptor IL-6R (sIL-6R); by an antibody to the IL-6 receptor; or by minocycline, which inhibits the microglia. IL-6 was localized in neurons of the spinal cord and, upon peripheral noxious stimulation in the presence of spinal TNF-alpha, IL-6 was released spinally. Furthermore, TNF-alpha recruited microglial cells to provide sIL-6R, which can form complexes with IL-6. Spinal application of IL-6 plus sIL-6R, but not of IL-6 alone, enhanced spinal hyperexcitability similar to TNF-alpha and the inhibition of TNF-alpha-induced hyperexcitability by minocycline was overcome by coadministration of sIL-6R, showing that sIL-6R is required. Neither minocycline nor the TNF-alpha-neutralizing compound etanercept inhibited the induction of hyperexcitability by IL-6 plus sIL-6R. Together, these data show that the induction of hyperexcitability of nociceptive deep dorsal horn neurons by TNF alpha largely depends on the formation of IL-6/sIL-6R complexes that are downstream of TNF-alpha and requires the interactions of neurons and microglia orchestrated by TNF-alpha. SIGNIFICANCE STATEMENT: Both spinal TNF-alpha and IL-6 induce a state of spinal hyperexcitability. We present the novel finding that the full effect of TNF-alpha on the development of spinal hyperexcitability depends on IL-6 trans-signaling acting downstream of TNF-alpha. IL-6 trans-signaling requires the formation of complexes of IL-6 and soluble IL-6 receptor. Spinal TNF alpha furthers the release of IL-6 from neurons in the spinal cord during peripheral noxious stimulation and recruits microglial cells to provide soluble IL-6 receptor, which can form complexes with IL-6. Therefore, a specific interaction between neurons and microglia is required for the full development of TNF-alpha-induced hyperexcitability of nociceptive deep horsal horn neurons. PMID- 27656017 TI - Schwann Cells in Neuromuscular Junction Formation and Maintenance. AB - The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation. SIGNIFICANCE STATEMENT: Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences of the ablation. This study reveals a critical role of SCs in NMJ formation as well as maintenance. PMID- 27656019 TI - DDX3 Modulates Neurite Development via Translationally Activating an RNA Regulon Involved in Rac1 Activation. AB - The RNA helicase DDX3 is a component of neuronal granules, and its gene mutations are linked to intellectual disability (ID). Here we demonstrate that DDX3 depletion in neurons impairs neurite development by downregulating Rac1 level and activation. Moreover, DDX3 activates the translation of functionally coherent mRNAs involved in Rac1 activation including Rac1 Among the DDX3 regulon, Prkaca encodes the catalytic subunit of PKA, a potential activator of Rac1 in neurons. DDX3-modulated PKAcalpha and Rac1 expression tunes the strength of PKA-Rac1 signaling and thereby contributes to neurite outgrowth and dendritic spine formation. Inhibition of DDX3 activity or expression in neonatal mice impaired dendritic outgrowth and spine formation of hippocampal neurons, echoing neuronal deficits underling DDX3 mutation-associated ID. Finally, we provide evidence that DDX3 activates local protein synthesis through a 5' UTR-dependent mechanism in neurons. The novel DDX3 regulon may conduct a spatial and temporal control of Rac1 signaling to regulate neurite development. SIGNIFICANCE STATEMENT: DDX3X mutations are linked to intellectual disability (ID). We provide first evidence that DDX3 is required for neurite outgrowth and dendritic spine formation in vitro and in vivo We identified a DDX3 regulon constituting functionally cohesive mRNAs involved in Rac1 signaling, which contributes to DDX3-modulated neurite development. Inhibition or ablation of DDX3 in vivo shortened neurite lengths and impaired dendritic spine formation in hippocampal neurons, reflecting the prevalence of ID-associated DDX3X mutations in the helicase domain. Mechanistically, DDX3 activates local protein synthesis of mRNAs sharing similar 5' UTR structures and therefore controls Rac1 signaling strength in neurites. PMID- 27656020 TI - Pattern Adaptation and Normalization Reweighting. AB - Adaptation to an oriented stimulus changes both the gain and preferred orientation of neural responses in V1. Neurons tuned near the adapted orientation are suppressed, and their preferred orientations shift away from the adapter. We propose a model in which weights of divisive normalization are dynamically adjusted to homeostatically maintain response products between pairs of neurons. We demonstrate that this adjustment can be performed by a very simple learning rule. Simulations of this model closely match existing data from visual adaptation experiments. We consider several alternative models, including variants based on homeostatic maintenance of response correlations or covariance, as well as feedforward gain-control models with multiple layers, and we demonstrate that homeostatic maintenance of response products provides the best account of the physiological data. SIGNIFICANCE STATEMENT: Adaptation is a phenomenon throughout the nervous system in which neural tuning properties change in response to changes in environmental statistics. We developed a model of adaptation that combines normalization (in which a neuron's gain is reduced by the summed responses of its neighbors) and Hebbian learning (in which synaptic strength, in this case divisive normalization, is increased by correlated firing). The model is shown to account for several properties of adaptation in primary visual cortex in response to changes in the statistics of contour orientation. PMID- 27656021 TI - Dysregulated NMDA-Receptor Signaling Inhibits Long-Term Depression in a Mouse Model of Fragile X Syndrome. AB - Fragile X syndrome (FXS) is a neurodevelopmental disease. It is one of the leading monogenic causes of intellectual disability among boys with most also displaying autism spectrum disorder traits. Here we investigated the role of NMDA receptors on mGluR-dependent long-term depression (mGluR-LTD), a key biomarker in the disease, at four different developmental stages. First, we applied the mGluR agonist 3,5-dihydroxyphenylglycine in the absence or presence of the NMDAR blocker, APV, hereby unmasking the NMDAR component in this process. As expected, in the presence of APV, we found more LTD in the mouse KO than in WT. This, however, was only observed in the p30-60 age group. At all other age groups tested, mGluR-LTD was almost identical between KO and WT. Interestingly, at p60, in the absence of APV, no or very little LTD was found in KO that was completely restored by application of APV. This suggests that the underlying cause of the enhanced mGluR-LTD in KO (at p30) is caused by dysregulated NMDAR signaling. To investigate this further, we next used NMDAR-subunit-specific antagonists. Inhibition of GluN2B, but not GluN2A, blocked mGluR-LTD only in WT. This was in contrast in the KO where blocking GluN2B rescued mGluR-LTD, suggesting GluN2B containing NMDARs in the KO are hyperactive. Thus, these findings suggest strong involvement of GluN2B-containing-NMDARs in the pathophysiology of FXS and highlight a potential path for treatment for the disease. SIGNIFICANCE STATEMENT: There is currently no cure for fragile X, although medications targeting specific FXS symptoms do exist. The FXS animal model, the Fmr1 knock-out mouse, has demonstrated an increased mGluR5-mediated long-term depression (LTD) leading to several clinical trials of mGluR5 inhibitors/modulators, yet all have failed. In addition, surprisingly little information exists about the possible role of other ion channels/receptors, including NMDA receptors (NMDAR), in mGluR-LTD. Here we focus on NMDARs and their regulation of mGluR-mediated LTD at different developmental stages using several different NMDAR blockers/antagonists. Our findings suggest dysregulated NMDARs in the pathophysiology of FXS leading to altered mGluR-mediated LTD. Together, these data will help to develop new drug candidates that could lead to reversal of the FXS phenotype. PMID- 27656023 TI - Necessary Contributions of Human Frontal Lobe Subregions to Reward Learning in a Dynamic, Multidimensional Environment. AB - Real-world decisions are typically made between options that vary along multiple dimensions, requiring prioritization of the important dimensions to support optimal choice. Learning in this setting depends on attributing decision outcomes to the dimensions with predictive relevance rather than to dimensions that are irrelevant and nonpredictive. This attribution problem is computationally challenging, and likely requires an interplay between selective attention and reward learning. Both these processes have been separately linked to the prefrontal cortex, but little is known about how they combine to support learning the reward value of multidimensional stimuli. Here, we examined the necessary contributions of frontal lobe subregions in attributing feedback to relevant and irrelevant dimensions on a trial-by-trial basis in humans. Patients with focal frontal lobe damage completed a demanding reward learning task where options varied on three dimensions, only one of which predicted reward. Participants with left lateral frontal lobe damage attributed rewards to irrelevant dimensions, rather than the relevant dimension. Damage to the ventromedial frontal lobe also impaired learning about the relevant dimension, but did not increase reward attribution to irrelevant dimensions. The results argue for distinct roles for these two regions in learning the value of multidimensional decision options under dynamic conditions, with the lateral frontal lobe required for selecting the relevant dimension to associate with reward, and the ventromedial frontal lobe required to learn the reward association itself. SIGNIFICANCE STATEMENT: The real world is complex and multidimensional; how do we attribute rewards to predictive features when surrounded by competing cues? Here, we tested the critical involvement of human frontal lobe subregions in a probabilistic, multidimensional learning environment, asking whether focal lesions affected trial-by-trial attribution of feedback to relevant and irrelevant dimensions. The left lateral frontal lobe was required for filtering option dimensions to allow appropriate feedback attribution, while the ventromedial frontal lobe was necessary for learning the value of features in the relevant dimension. These findings argue that selective attention and associative learning processes mediated by anatomically distinct frontal lobe subregions are both critical for adaptive choice in more complex, ecologically valid settings. PMID- 27656022 TI - Adult Brain Serotonin Deficiency Causes Hyperactivity, Circadian Disruption, and Elimination of Siestas. AB - Serotonin (5-HT) is a crucial neuromodulator linked to many psychiatric disorders. However, after more than 60 years of study, its role in behavior remains poorly understood, in part because of a lack of methods to target 5-HT synthesis specifically in the adult brain. Here, we have developed a genetic approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system by stereotaxic injection of an adeno associated virus expressing Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele. We investigated the behavioral effects of deficient brain 5-HT synthesis and discovered a unique composite phenotype. Surprisingly, adult 5-HT deficiency did not affect anxiety-like behavior, but resulted in a robust hyperactivity phenotype in novel and home cage environments. Moreover, loss of 5-HT led to an altered pattern of circadian behavior characterized by an advance in the onset and a delay in the offset of daily activity, thus revealing a requirement for adult 5-HT in the control of daily activity patterns. Notably, after normalizing for hyperactivity, we found that the normal prolonged break in nocturnal activity (siesta), a period of rapid eye movement (REM) and non-REM sleep, was absent in all animals in which 5-HT deficiency was verified. Our findings identify adult 5 HT as a requirement for siestas, implicate adult 5-HT in sleep-wake homeostasis, and highlight the importance of our adult-specific 5-HT-synthesis-targeting approach in understanding 5-HT's role in controlling behavior. SIGNIFICANCE STATEMENT: Serotonin (5-HT) is a crucial neuromodulator, yet its role in behavior remains poorly understood, in part because of a lack of methods to target specifically adult brain 5-HT synthesis. We developed an approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system. Using this technique, we discovered that adult 5-HT deficiency led to a novel compound phenotype consisting of hyperactivity, disrupted circadian behavior patterns, and elimination of siestas, a period of increased sleep during the active phase. These findings highlight the importance of our approach in understanding 5-HT's role in behavior, especially in controlling activity levels, circadian behavior, and sleep-wake homeostasis, behaviors that are disrupted in many psychiatric disorders such as attention deficit hyperactivity disorder. PMID- 27656026 TI - Eye Can Hear Clearly Now: Inverse Effectiveness in Natural Audiovisual Speech Processing Relies on Long-Term Crossmodal Temporal Integration. AB - Speech comprehension is improved by viewing a speaker's face, especially in adverse hearing conditions, a principle known as inverse effectiveness. However, the neural mechanisms that help to optimize how we integrate auditory and visual speech in such suboptimal conversational environments are not yet fully understood. Using human EEG recordings, we examined how visual speech enhances the cortical representation of auditory speech at a signal-to-noise ratio that maximized the perceptual benefit conferred by multisensory processing relative to unisensory processing. We found that the influence of visual input on the neural tracking of the audio speech signal was significantly greater in noisy than in quiet listening conditions, consistent with the principle of inverse effectiveness. Although envelope tracking during audio-only speech was greatly reduced by background noise at an early processing stage, it was markedly restored by the addition of visual speech input. In background noise, multisensory integration occurred at much lower frequencies and was shown to predict the multisensory gain in behavioral performance at a time lag of ~250 ms. Critically, we demonstrated that inverse effectiveness, in the context of natural audiovisual (AV) speech processing, relies on crossmodal integration over long temporal windows. Our findings suggest that disparate integration mechanisms contribute to the efficient processing of AV speech in background noise. SIGNIFICANCE STATEMENT: The behavioral benefit of seeing a speaker's face during conversation is especially pronounced in challenging listening environments. However, the neural mechanisms underlying this phenomenon, known as inverse effectiveness, have not yet been established. Here, we examine this in the human brain using natural speech-in-noise stimuli that were designed specifically to maximize the behavioral benefit of audiovisual (AV) speech. We find that this benefit arises from our ability to integrate multimodal information over longer periods of time. Our data also suggest that the addition of visual speech restores early tracking of the acoustic speech signal during excessive background noise. These findings support and extend current mechanistic perspectives on AV speech perception. PMID- 27656024 TI - Optimized Parallel Coding of Second-Order Stimulus Features by Heterogeneous Neural Populations. AB - Efficient processing of sensory input is essential to ensure an organism's survival in its natural environment. Growing evidence suggests that sensory neurons can optimally encode natural stimuli by ensuring that their tuning opposes stimulus statistics, such that the resulting neuronal response contains equal power at all frequencies (i.e., is "white"). Such temporal decorrelation or whitening has been observed across modalities, but the effects of neural heterogeneities on determining tuning and thus responses to natural stimuli have not been investigated. Here, we investigate how heterogeneities in sensory pyramidal neurons organized in three parallel maps representing the body surface determine responses to second-order electrosensory stimulus features in the weakly electric fish Apteronotus leptorhynchus While some sources of heterogeneities such as ON- and OFF-type responses to first-order did not affect responses to second-order electrosensory stimulus features, other sources of heterogeneity within and across the maps strongly determined responses. We found that these cells effectively performed a fractional differentiation operation on their input with exponents ranging from zero (no differentiation) to 0.4 (strong differentiation). Varying adaptation in a simple model explained these heterogeneities and predicted a strong correlation between fractional differentiation and adaptation. Using natural stimuli, we found that only a small fraction of neurons implemented temporal whitening. Rather, a large fraction of neurons did not perform any significant whitening and thus preserved natural input statistics in their responses. We propose that this information is needed to properly decode optimized information sent in parallel through temporally whitened responses based on context. SIGNIFICANCE STATEMENT: We demonstrate that heterogeneities in the same sensory neuron type can either have no or significant influence on their responses to second-order stimulus features. While an ON- or OFF-type response to first-order stimulus attributes has no significant influence on responses to second-order stimulus features, we found that only a small fraction of sensory neurons optimally encoded natural stimuli through high-pass filtering, thereby implementing temporal whitening. Surprisingly, a large fraction of sensory neurons performed little if no filtering of stimuli, thereby preserving natural stimulus statistics. We hypothesize that this pathway is necessary to properly decode optimized information contained in temporally whitened responses based on context. PMID- 27656025 TI - The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA Induced Dyskinesia in Parkinsonian Rats. AB - Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. SIGNIFICANCE STATEMENT: Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease itself. Although dyskinesia is associated with dynamic changes in primary motor cortex physiology, to date, there are no published studies investigating in vivo neurotransmitter release in M1 during dyskinesia. In parkinsonian rats, l-DOPA administration reduced M1 glutamate efflux and enhanced GABA efflux, coincident with the emergence of dyskinetic behaviors. Dyskinesia could be reduced by local M1 modulation of D1, AMPA, and GABAA receptors, providing preclinical support for the notion that exogenously blunting M1 signaling (pharmacologically or with cortical stimulation) is a therapeutic approach to the treatment of debilitating dyskinesias. PMID- 27656027 TI - Reduced Efficacy of Anti-Abeta Immunotherapy in a Mouse Model of Amyloid Deposition and Vascular Cognitive Impairment Comorbidity. AB - Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti Abeta immunotherapy, which uses antibodies against Abeta to clear it from the brain. While successful in clearing Abeta and improving cognition in mice, anti Abeta immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti Abeta immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID comorbidity in the AD population. We used our unique model of VCID-amyloid comorbidity to test this hypothesis. We placed 9-month-old wild-type and APP/PS1 mice on either a control diet or a diet that induces hyperhomocysteinemia (HHcy). After being placed on the diet for 3 months, the mice then received intraperotineal injections of either IgG2a control or 3D6 for another 3 months. While we found that treatment of our comorbidity model with 3D6 resulted in decreased total Abeta levels, there was no cognitive benefit of the anti-Abeta immunotherapy in our AD/VCID mice. Further, microhemorrhages were increased by 3D6 in the APP/PS1/control but further increased in an additive fashion when 3D6 was administered to the APP/PS1/HHcy mice. This suggests that the use of anti-Abeta immunotherapy in patients with both AD and VCID would be ineffective on cognitive outcomes. SIGNIFICANCE STATEMENT: Despite significant mouse model data demonstrating both pathological and cognitive efficacy of anti Abeta immunotherapy for the treatment of Alzheimer's disease, clinical trial outcomes have been underwhelming, failing to meet any primary endpoints. We show here that vascular cognitive impairment and dementia (VCID) comorbidity eliminates cognitive efficacy of anti-Abeta immunotherapy, despite amyloid clearance. Further, cerebrovascular adverse events of the anti-Abeta immunotherapy are significantly exacerbated by the VCID comorbidity. These data suggest that VCID comorbidity with Alzheimer's disease may mute the response to anti-Abeta immunotherapy. PMID- 27656029 TI - The Nature of the Sensory Input to the Neonatal Rat Barrel Cortex. AB - Sensory input plays critical roles in the development of the somatosensory cortex during the neonatal period. This early sensory input may involve: (1) stimulation arising from passive interactions with the mother and littermates and (2) sensory feedback arising from spontaneous infant movements. The relative contributions of these mechanisms under natural conditions remain largely unknown, however. Here, we show that, in the whisker-related barrel cortex of neonatal rats, spontaneous whisker movements and passive stimulation by the littermates cooperate, with comparable efficiency, in driving cortical activity. Both tactile signals arising from the littermate's movements under conditions simulating the littermates' position in the litter, and spontaneous whisker movements efficiently triggered bursts of activity in barrel cortex. Yet, whisker movements with touch were more efficient than free movements. Comparison of the various experimental conditions mimicking the natural environment showed that tactile signals arising from the whisker movements with touch and stimulation by the littermates, support: (1) a twofold higher level of cortical activity than in the isolated animal, and (2) a threefold higher level of activity than in the deafferented animal after the infraorbital nerve cut. Together, these results indicate that endogenous (self generated movements) and exogenous (stimulation by the littermates) mechanisms cooperate in driving cortical activity in newborn rats and point to the importance of the environment in shaping cortical activity during the neonatal period. SIGNIFICANCE STATEMENT: Sensory input plays critical roles in the development of the somatosensory cortex during the neonatal period. However, the origins of sensory input to the neonatal somatosensory cortex in the natural environment remain largely unknown. Here, we show that in the whisker-related barrel cortex of neonatal rats, spontaneous whisker movements and passive stimulation by the littermates cooperate, with comparable efficiency, in driving cortical activity during the critical developmental period. PMID- 27656028 TI - Slow Temporal Integration Enables Robust Neural Coding and Perception of a Cue to Sound Source Location. AB - In mammals, localization of sound sources in azimuth depends on sensitivity to interaural differences in sound timing (ITD) and level (ILD). Paradoxically, while typical ILD-sensitive neurons of the auditory brainstem require millisecond synchrony of excitatory and inhibitory inputs for the encoding of ILDs, human and animal behavioral ILD sensitivity is robust to temporal stimulus degradations (e.g., interaural decorrelation due to reverberation), or, in humans, bilateral clinical device processing. Here we demonstrate that behavioral ILD sensitivity is only modestly degraded with even complete decorrelation of left- and right-ear signals, suggesting the existence of a highly integrative ILD-coding mechanism. Correspondingly, we find that a majority of auditory midbrain neurons in the central nucleus of the inferior colliculus (of chinchilla) effectively encode ILDs despite complete decorrelation of left- and right-ear signals. We show that such responses can be accounted for by relatively long windows of bilateral excitatory-inhibitory interaction, which we explicitly measure using trains of narrowband clicks. Neural and behavioral data are compared with the outputs of a simple model of ILD processing with a single free parameter, the duration of excitatory-inhibitory interaction. Behavioral, neural, and modeling data collectively suggest that ILD sensitivity depends on binaural integration of excitation and inhibition within a ?3 ms temporal window, significantly longer than observed in lower brainstem neurons. This relatively slow integration potentiates a unique role for the ILD system in spatial hearing that may be of particular importance when informative ITD cues are unavailable. SIGNIFICANCE STATEMENT: In mammalian hearing, interaural differences in the timing (ITD) and level (ILD) of impinging sounds carry critical information about source location. However, natural sounds are often decorrelated between the ears by reverberation and background noise, degrading the fidelity of both ITD and ILD cues. Here we demonstrate that behavioral ILD sensitivity (in humans) and neural ILD sensitivity (in single neurons of the chinchilla auditory midbrain) remain robust under stimulus conditions that render ITD cues undetectable. This result can be explained by "slow" temporal integration arising from several-millisecond-long windows of excitatory-inhibitory interaction evident in midbrain, but not brainstem, neurons. Such integrative coding can account for the preservation of ILD sensitivity despite even extreme temporal degradations in ecological acoustic stimuli. PMID- 27656030 TI - Calpain Activation in Alzheimer's Model Mice Is an Artifact of APP and Presenilin Overexpression. AB - Intraneuronal calcium stimulates the calpain-dependent conversion of p35 to p25, a CDK5 activator. It is widely believed that amyloid beta peptide (Abeta) induces this conversion that, in turn, has an essential role in Alzheimer's disease pathogenesis. However, in vivo studies on p25 generation used transgenic mice overexpressing mutant amyloid precursor protein (APP) and presenilin (PS). Here, using single App knock-in mice, we show that p25 generation is an artifact caused by membrane protein overexpression. We show that massive Abeta42 accumulation without overexpression of APP or presenilin does not produce p25, whereas p25 generation occurred with APP/PS overexpression and in postmortem mouse brain. We further support this finding using mice deficient for calpastatin, the sole calpain-specific inhibitor protein. Thus, the intracerebral environment of the APP/PS mouse brain and postmortem brain is an unphysiological state. SIGNIFICANCE STATEMENT: We recently estimated using single App knock-in mice that accumulate amyloid beta peptide without transgene overexpression that 60% of the phenotypes observed in Alzheimer's model mice overexpressing mutant amyloid precursor protein (APP) or APP and presenilin are artifacts (Saito et al., 2014). The current study further supports this estimate by invalidating key results from papers that were published in Cell These findings suggest that more than 3000 publications based on APP and APP/PS overexpression must be reevaluated. PMID- 27656032 TI - Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence. AB - Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that DeltaFosB in the nucleus accumbens (NAc) is a key mediator of this cross sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced DeltaFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, DeltaFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience. SIGNIFICANCE STATEMENT: Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior, followed by a period of abstinence from sexual behavior, causes increased reward for amphetamine in male rats. This study demonstrates that activation of ventral tegmental area dopamine neurons during sexual experience regulates cross-sensitization of amphetamine reward. Finally, ventral tegmental area dopamine cell activation is essential for experience-induced neural adaptations in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. These findings demonstrate a role of mesolimbic dopamine in the interaction between natural and drug rewards, and identify mesolimbic dopamine as a key mediator of changes in vulnerability for drug use after loss of natural reward. PMID- 27656031 TI - Stress-Induced Reinstatement of Nicotine Preference Requires Dynorphin/Kappa Opioid Activity in the Basolateral Amygdala. AB - The dynorphin (DYN)/kappa-opioid receptor (KOR) system plays a conserved role in stress-induced reinstatement of drug seeking for prototypical substances of abuse. Due to nicotine's high propensity for stress-induced relapse, we hypothesized that stress would induce reinstatement of nicotine seeking-like behavior in a KOR-dependent manner. Using a conditioned place preference (CPP) reinstatement procedure in mice, we show that both foot-shock stress and the pharmacological stressor yohimbine (2 mg/kg, i.p.) induce reinstatement of nicotine CPP in a norbinaltorphimine (norBNI, a KOR antagonist)-sensitive manner, indicating that KOR activity is necessary for stress-induced nicotine CPP reinstatement. After reinstatement testing, we visualized robust c-fos expression in the basolateral amygdala (BLA), which was reduced in mice pretreated with norBNI. We then used several distinct but complementary approaches of locally disrupting BLA KOR activity to assess the role of KORs and KOR-coupled intracellular signaling cascades on reinstatement of nicotine CPP. norBNI injected locally into the BLA prevented yohimbine-induced nicotine CPP reinstatement without affecting CPP acquisition. Similarly, selective deletion of BLA KORs in KOR conditional knock-out mice prevented foot-shock-induced CPP reinstatement. Together, these findings strongly implicate BLA KORs in stress induced nicotine seeking-like behavior. In addition, we found that chemogenetic activation of Galphai signaling within CaMKIIalpha BLA neurons was sufficient to induce nicotine CPP reinstatement, identifying an anatomically specific intracellular mechanism by which stress leads to reinstatement. Considered together, our findings suggest that activation of the DYN/KOR system and Galphai signaling within the BLA is both necessary and sufficient to produce reinstatement of nicotine preference. SIGNIFICANCE STATEMENT: Considering the major impact of nicotine use on human health, understanding the mechanisms by which stress triggers reinstatement of drug-seeking behaviors is particularly pertinent to nicotine. The dynorphin (DYN)/kappa-opioid receptor (KOR) system has been implicated in stress-induced reinstatement of drug seeking for other commonly abused drugs. However, the specific role, brain region, and mechanisms that this system plays in reinstatement of nicotine seeking has not been characterized. Here, we report region-specific engagement of the DYN/KOR system and subsequent activation of inhibitory (Gi-linked) intracellular signaling pathways within the basolateral amygdala during stress-induced reinstatement of nicotine preference. We show that the DYN/KOR system is necessary to produce this behavioral state. This work may provide novel insight for the development of therapeutic approaches to prevent stress-related nicotine relapse. PMID- 27656034 TI - Hyperspectral Imaging of Neoplastic Progression in a Mouse Model of Oral Carcinogenesis. AB - Hyperspectral imaging (HSI) is an emerging modality for medical applications and holds great potential for noninvasive early detection of cancer. It has been reported that early cancer detection can improve the survival and quality of life of head and neck cancer patients. In this paper, we explored the possibility of differentiating between premalignant lesions and healthy tongue tissue using hyperspectral imaging in a chemical induced oral cancer animal model. We proposed a novel classification algorithm for cancer detection using hyperspectral images. The method detected the dysplastic tissue with an average area under the curve (AUC) of 0.89. The hyperspectral imaging and classification technique may provide a new tool for oral cancer detection. PMID- 27656033 TI - Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury. AB - After traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is promptly activated after TBI, it is unknown whether it has a significant role in chronic phases of TBI (>1 year after injury). Using a closed head injury model of TBI in mice, we showed by MRI scans that TBI caused substantial degeneration at the lesion site within a few weeks and these did not expand significantly thereafter. However, chronic alterations in neurons were observed, with reduced dendritic spine density lasting >1 year after injury. In parallel, we found a long-lasting inflammatory response throughout the entire brain. Deletion of one allele of CX3CR1, a chemokine receptor, limited infiltration of peripheral immune cells and largely prevented the chronic degeneration of the injured brain and provided a better functional recovery in female, but not male, mice. Therefore, targeting persistent neuroinflammation presents a new therapeutic option to reduce chronic neurodegeneration. SIGNIFICANCE STATEMENT: Traumatic brain injury (TBI) often causes chronic neurological problems including epilepsy, neuropsychiatric disorders, and dementia through unknown mechanisms. Our study demonstrates that inflammatory cells invading the brain lead to secondary brain damage. Sex-specific amelioration of chronic neuroinflammation rescues the brain degeneration and results in improved motor functions. Therefore, this study pinpoints an effective therapeutic approach to preventing secondary complications after TBI. PMID- 27656035 TI - Superpixel-based spectral classification for the detection of head and neck cancer with hyperspectral imaging. AB - Hyperspectral imaging (HSI) is an emerging imaging modality for medical applications. HSI acquires two dimensional images at various wavelengths. The combination of both spectral and spatial information provides quantitative information for cancer detection and diagnosis. This paper proposes using superpixels, principal component analysis (PCA), and support vector machine (SVM) to distinguish regions of tumor from healthy tissue. The classification method uses 2 principal components decomposed from hyperspectral images and obtains an average sensitivity of 93% and an average specificity of 85% for 11 mice. The hyperspectral imaging technology and classification method can have various applications in cancer research and management. PMID- 27656037 TI - Geographical Mobility, Income, Life Satisfaction and Family Size Preferences: An Empirical Study on Rural Households in Shaanxi and Henan Provinces in China. AB - Employing data from the China rural-urban mobility survey conducted in 2010, this study investigates the influence of family demographic characteristics on the income, life satisfaction, and potential for rural-urban mobility at the rural household level of two provinces of China: Shaanxi and Henan. A larger labor force in a rural household was found to reduce a family's ability or inclination to move to a city. The findings reveal that family size negatively affects the average income per family member and reduces the marginal income of the labor force and that minor children can improve the life satisfaction of family members. We conclude that a larger family size does not translate to more benefits for a rural household. Family size preference is found to be a reflection of parents' concerns about elderly care and is deemed to be unfavorable for urbanization in P. R. China. PMID- 27656038 TI - Approximate chemical analysis of volcanic glasses using Raman spectroscopy. AB - The effect of chemical composition on the Raman spectra of a series of natural calcalkaline silicate glasses has been quantified by performing electron microprobe analyses and obtaining Raman spectra on glassy filaments (~450 um) derived from a magma mingling experiment. The results provide a robust compositionally-dependent database for the Raman spectra of natural silicate glasses along the calcalkaline series. An empirical model based on both the acquired Raman spectra and an ideal mixing equation between calcalkaline basaltic and rhyolitic end-members is constructed enabling the estimation of the chemical composition and degree of polymerization of silicate glasses using Raman spectra. The model is relatively insensitive to acquisition conditions and has been validated using the MPI-DING geochemical standard glasses1 as well as further samples. The methods and model developed here offer several advantages compared with other analytical and spectroscopic methods such as infrared spectroscopy, X ray fluorescence spectroscopy, electron and ion microprobe analyses, inasmuch as Raman spectroscopy can be performed with a high spatial resolution (1 um2) without the need for any sample preparation as a nondestructive technique. This study represents an advance in efforts to provide the first database of Raman spectra for natural silicate glasses and yields a new approach for the treatment of Raman spectra, which allows us to extract approximate information about the chemical composition of natural silicate glasses using Raman spectroscopy. We anticipate its application in handheld in situ terrestrial field studies of silicate glasses under extreme conditions (e.g. extraterrestrial and submarine environments). PMID- 27656036 TI - Quantitative Diagnosis of Tongue Cancer from Histological Images in an Animal Model. AB - We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing. Representative areas of hematoxylin and eosin (H&E) stained tissue from tongue sections were captured for classifying tumor and non tumor tissue. The image set used in this paper consisted of 214 color images (114 tumor and 100 normal tissue samples). A total of 738 color, texture, morphometry and topology features were extracted from the histological images. The combination of image features from epithelium tissue and its constituent nuclei and cytoplasm has been demonstrated to improve the classification results. With ten iteration nested cross validation, the method achieved an average sensitivity of 96.5% and a specificity of 99% for tongue cancer detection. The next step of this research is to apply this approach to human tissue for computer aided diagnosis of tongue cancer. PMID- 27656039 TI - Methods of mapping ethnographic data on migration, tourism labor, and health risk in the Dominican Republic. AB - This paper focuses on a mixed-method approach to quantifying qualitative data from the results of an ongoing NIDA-funded ethnographic study entitled "Migration, Tourism, and the HIV/Drug-Use Syndemic in the Dominican Republic". This project represents the first large-scale mixed method study to identify social, structural, environmental, and demographic factors that may contribute to ecologies of health vulnerability within the Caribbean tourism zones. Our research has identified deportation history as a critical factor contributing to vulnerability to HIV, drugs, mental health problems, and other health conditions. Therefore, understanding the movements of our participants became a vital aspect of this research. This paper describes how we went about translating 37 interviews into visual geographic representations. These methods help develop possible strategies for confronting HIV/AIDS and problematic substance use by examining the ways that these epidemics are shaped by the realities of people's labor migration and the spaces they inhabit. Our methods for mapping this qualitative data contribute to the ongoing, broadening capabilities of using GIS in social science research. A key contribution of this work is its integration of different methodologies from various disciplines to help better understand complex social problems. PMID- 27656040 TI - A preliminary assessment of water partitioning and ecohydrological coupling in northern headwaters using stable isotopes and conceptual runoff models. AB - We combined a conceptual rainfall-runoff model and input-output relationships of stable isotopes to understand ecohydrological influences on hydrological partitioning in snow-influenced northern catchments. Six sites in Sweden (Krycklan), Canada (Wolf Creek; Baker Creek; Dorset), Scotland (Girnock) and the USA (Dry Creek) span moisture and energy gradients found at high latitudes. A meta-analysis was carried out using the Hydrologiska Byrans Vattenbalansavdelning (HBV) model to estimate the main storage changes characterizing annual water balances. Annual snowpack storage importance was ranked as Wolf Creek > Krycklan > Dorset > Baker Creek > Dry Creek > Girnock. The subsequent rate and longevity of melt were reflected in calibrated parameters that determine partitioning of waters between more rapid and slower flowpaths and associated variations in soil and groundwater storage. Variability of stream water isotopic composition depends on the following: (i) rate and duration of spring snowmelt; (ii) significance of summer/autumn rainfall; and (iii) relative importance of near-surface and deeper flowpaths in routing water to the stream. Flowpath partitioning also regulates influences of summer evaporation on drainage waters. Deviations of isotope data from the Global Meteoric Water Line showed subtle effects of internal catchment processes on isotopic fractionation most likely through evaporation. Such effects are highly variable among sites and with seasonal differences at some sites. After accounting for climate, evaporative fractionation is strongest at sites where lakes and near-surface runoff processes in wet riparian soils can mobilize isotopically enriched water during summer and autumn. Given close soil-vegetation coupling, this may result in spatial variability in soil water isotope pools available for plant uptake. We argue that stable isotope studies are crucial in addressing the many open questions on hydrological functioning of northern environments. (c) 2015 The Authors. Hydrological Processes published by John Wiley & Sons Ltd. PMID- 27656041 TI - Attitudes, Perceptions, and Utilization of Evidence-Based Practices in Residential Care. AB - This study reports on results of a national survey conducted in the United States about the attitudes, perceptions and utilization of evidence-based practices (EBPs) in residential care settings. Seventy-five of 118 member agencies (63.6% response rate) of a voluntary national residential care association responded to a web-administered structured survey, which included the Evidence-Based Practices Attitude Scale (Aarons, 2004). Results show overwhelmingly positive attitudes toward EBPs. Concerns were reported mainly with regard to cost and impeding a client-driven practice approach. The study also showed a high degree of utilization of EBPs with over 88 percent of programs reporting the use of at least one practice they considered to be evidence-based. Altogether 53 different practices were reported although it is unknown at this point whether practices were delivered with fidelity. Behaviorally-based and trauma-focused interventions constituted the most common interventions used by residential care agencies. Practices were subsequently validated against four national clearinghouse sites, indicating that only slightly over half of all reported practices had been evaluated by at least one clearinghouse and rated as having some research evidence for effectiveness. Divergent views about what practices are evidence based point to the need for continued discussion between the practice and research fields about conceptualizations of evidence. PMID- 27656042 TI - Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene). AB - Poly(ethylene dioxythiophene) with functional pendant groups bearing double bonds is synthesized and employed for the fabrication of electroactive hydrogels with advantageous characteristics: covalently cross-linked porous 3D scaffolds with notable swelling ratio, appropriate mechanical properties, electroactivity in physiological conditions, and suitability for proliferation and differentiation of C2C12 cells. This is a new approach for the fabrication of conductive engineered constructs. PMID- 27656043 TI - Perspectives on CMIP5 model performance in the Nile River headwaters regions. AB - Ranking the performance of global climate models (GCMs) is a notoriously difficult exercise. Multi-model comparison studies nearly always show that each model has strengths and weaknesses relative to others, and for many purposes the multi-model ensemble mean delivers better estimates than any individual model. Nevertheless, in regions like East Africa, where there is little consensus between models on the magnitude or sign of 21st century precipitation change, the multi-model ensemble mean approach to climate projection provides little value for adaptation planning. Here, we consider several possible frameworks for model evaluation and ranking, and assess the differences in performance of a subset of models participating in the 5th Coupled Model Intercomparison Project (CMIP5) according to each framework. Our test case is precipitation in the Nile River headwaters regions. We find that there is little consistency in the relative performance of models across frameworks based on amount and seasonality of precipitation, interannual precipitation variability, precipitation teleconnections, and continental scale climate patterns. These analyses offer some guidance on which GCMs are most likely to provide meaningful results for specific applications, but they caution that any effort to select 'best performing' GCMs for the Nile River basin must carefully consider the purposes for which GCMs are being selected. PMID- 27656044 TI - Influence of cigarette smoking on ALS outcome: a population-based study. AB - OBJECTIVE: To assess the prognostic influence of premorbid smoking habits and vascular risk profile on amyotrophic lateral sclerosis (ALS) phenotype and outcome in a population-based cohort of Italian patients. METHODS: A total of 650 patients with ALS from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid cigarette smoking habits and chronic obstructive pulmonary disease (COPD) were collected at the time of diagnosis. RESULTS: Current smokers had a significantly shorter median survival (1.9 years, IQR 1.2-3.4) compared with former (2.3 years, IQR 1.5 4.2) and never smokers (2.7 years, IQR 1.8-4.6) (p=0.001). Also COPD adversely influenced patients' prognosis. Both smoking habits and CODP were retained in Cox multivariable model. CONCLUSIONS: This study has demonstrated in a large population-based cohort of patients with ALS that cigarette smoking is an independent negative prognostic factor for survival, with a dose-response gradient. Its effect is not related to the presence of COPD or to respiratory status at time of diagnosis. The understanding of the mechanisms, either genetic or epigenetic, through which exogenous factors influence disease phenotype is of major importance towards a more focused approach to cure ALS. PMID- 27656045 TI - Metabolic syndrome is related to polyneuropathy and impaired peripheral nerve function: a prospective population-based cohort study. AB - OBJECTIVE: Diabetes mellitus is a known risk factor for polyneuropathy, but the role of pre-diabetes and metabolic syndrome remains unclear. We aimed to investigate the role of these factors in a community-dwelling middle-aged and elderly population. METHODS: 1256 participants of the population-based Rotterdam Study (mean age 70.0, 54.5% females) were screened for polyneuropathy with a questionnaire, neurological examination and nerve conduction studies. Data on type 2 diabetes and components of metabolic syndrome were also collected. Logistic regression was used to investigate associations of diabetes, pre diabetes and metabolic syndrome and its separate components with polyneuropathy. Linear regression was used to investigate associations with nerve conduction parameters in participants without polyneuropathy. FINDINGS: Diabetes was associated with polyneuropathy (OR 3.01, 95% CI 1.60 to 5.65), while impaired fasting glucose was not (OR 1.55, 95% CI 0.70 to 3.44). Metabolic syndrome was associated with polyneuropathy (OR 1.92, 95% CI 1.09 to 3.38), with a stronger association when more components of the syndrome were present. Analysing separate components of metabolic syndrome revealed associations for elevated waist circumference (OR 2.84, 95% CI 1.35 to 5.99) and elevated triglycerides (OR 2.01, 95% CI 1.11 to 3.62). Similar associations were found after excluding participants with diabetes. In participants without polyneuropathy, metabolic syndrome associated with lower sural sensory nerve action potential amplitudes. CONCLUSIONS: Metabolic syndrome, abdominal obesity and dyslipidaemia, are strongly associated with polyneuropathy, irrespective of the presence of diabetes. Metabolic syndrome also associates with impaired nerve function in people without polyneuropathy. Our study therefore suggests that cardiometabolic disturbances have an impact on peripheral nerve function that extends beyond clinically manifest disease. PMID- 27656046 TI - Challenges of a transition to a sustainably managed shrimp culture agro-ecosystem in the Mahakam delta, East Kalimantan, Indonesia. AB - Around 1990, when in other countries mangrove protection took off, massive conversion of mangrove forest into shrimp ponds started in the Mahakam delta. To identify constraints to and options for sustainable management we analysed institutions and constraints with stakeholders. In 3 sites we used participatory tools and a complementary survey to assess the livelihood framework. Since 1970, ponds for shrimp farming gradually replaced 75% of mangrove forested area. After 2004, recovery of mangrove took off, as, mainly due to low shrimp yields, ponds were abandoned. In 2008, 54% of the delta was dedicated to ponds for shrimp production. Around 80% of livelihood activities of pond-farmers, pond caretakers, and fishermen was related to mangroves. The involvement of men and women in these activities varied between sites and types. Poor households depended more on mangroves. Most activities resulted in seasonal income peaks; only a few activities resulted in a full daily livelihood. Ponds, on the other hand, provide 50% of households' livelihood, but this remains vulnerable in the context of the risky shrimp production. Skewed land holding, unequal sharing of benefits, competing claims and vested interests of stakeholders pose a great challenge to a transition to a more sustainable use of the mangrove area. In particular, ponds located on peat soils are non-sustainable and would require full restoration into mangrove; ponds on other soils could best be transformed into a mixed mangrove pond system using a 'green-water' technology. PMID- 27656048 TI - Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics. AB - Background and Objective. Inflammation is central in the pathogenesis of pulmonary hypertension. We investigated how serum cytokines correlate with clinical features, hemodynamics, and lung histology in young patients with pulmonary hypertension associated with congenital cardiac shunts. Design. Prospective, observational study. Methods and Results. Patients (n = 44) were aged 2.6 to 37.6 months. Group I patients (n = 31) were characterized by pulmonary congestion and higher pulmonary blood flow compared to group II (p = 0.022), with no need for preoperative cardiac catheterization. Group II patients (n = 13) had no congestive features. At catheterization, they had elevated pulmonary vascular resistance (5.7 [4.4-7.4] Wood units.m2, geometric mean with 95% CI). Cytokines were measured by chemiluminescence. Macrophage migration inhibitory factor (MIF) was found to be inversely related to pulmonary blood flow (r = -0.33, p = 0.026) and was higher in group II (high pulmonary vascular resistance) compared to group I (high pulmonary blood flow) (p = 0.017). In contrast, RANTES chemokine (regulated on activation, normal T cell expressed and secreted) was characteristically elevated in Group I (p = 0.022). Interleukin 16 was also negatively related to pulmonary blood flow (rS = -0.33, p = 0.029) and was higher in patients with obstructive vasculopathy at intraoperative lung biopsy (p = 0.021). Conclusion. Cytokines seem to be important and differentially regulated in subpopulations of young patients with cardiac shunts. PMID- 27656047 TI - Anti-Inflammatory Effects of Hyperbaric Oxygenation during DSS-Induced Colitis in BALB/c Mice Include Changes in Gene Expression of HIF-1alpha, Proinflammatory Cytokines, and Antioxidative Enzymes. AB - Reactive oxygen species (ROS) and nitrogen species have an indispensable role in regulating cell signalling pathways, including transcriptional control via hypoxia inducible factor-1alpha (HIF-1alpha). Hyperbaric oxygenation treatment (HBO2) increases tissue oxygen content and leads to enhanced ROS production. In the present study DSS-induced colitis has been employed in BALB/c mice as an experimental model of gut mucosa inflammation to investigate the effects of HBO2 on HIF-1alpha, antioxidative enzyme, and proinflammatory cytokine genes during the colonic inflammation. Here we report that HBO2 significantly reduces severity of DSS-induced colitis, as evidenced by the clinical features, histological assessment, impaired immune cell expansion and mobilization, and reversal of IL 1beta, IL-2, and IL-6 gene expression. Gene expression and antioxidative enzyme activity were changed by the HBO2 and the inflammatory microenvironment in the gut mucosa. Strong correlation of HIF-1alpha mRNA level to GPx1, SOD1, and IL-6 mRNA expression suggests involvement of HIF-1alpha in transcriptional regulation of these genes during colonic inflammation and HBO2. This is further confirmed by a strong correlation of HIF-1alpha with known target genes VEGF and PGK1. Results demonstrate that HBO2 has an anti-inflammatory effect in DSS-induced colitis in mice, and this effect is at least partly dependent on expression of HIF-1alpha and antioxidative genes. PMID- 27656049 TI - Myeloperoxidase-Oxidized LDLs Enhance an Anti-Inflammatory M2 and Antioxidant Phenotype in Murine Macrophages. AB - Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. LDLs can be oxidized not only chemically by copper (Ox-LDLs) but also enzymatically by myeloperoxidase (MpOx-LDLs) resulting in oxidized LDLs poor in lipid peroxides. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. In this study, the effects of LDLs on macrophage polarization were investigated by monitoring the expression of M1 and M2 genes following stimulation with native LDLs, Ox-LDLs, or MpOx-LDLs in RAW 264.7 cells. Except for MRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatory Arg1 expression in M2 cells and also in the other phenotypes. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. These data were largely confirmed in murine bone marrow derived macrophages. Our data suggest that MpOx-LDLs were the most efficient to accumulate within cells and to enhance an anti-inflammatory and antioxidant phenotype in M2 cells and also in the other macrophage phenotypes. PMID- 27656050 TI - Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease. AB - Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed. PMID- 27656051 TI - Acculturation and Health Insurance of Mexicans in the USA. AB - We study how the health insurance coverage of Mexican immigrants changes with time in the U.S. Cross sectional estimates indicate that time since arrival is negatively correlated with the probability of being uninsured for both male and female Mexican immigrants, and about a third of the decline could be attributed to civic and labor market incorporation of Mexican immigrants. However, much of the relationship between time in the U.S. and health insurance coverage, after adjusting for demographic and labor market factors, is due to failure to control for age at arrival and period of arrival. Estimates from longitudinal analyses suggest that there is no systematic relationship between time in the U.S. and health insurance of Mexican immigrants, although imprecision in the fixed effects estimates makes it difficult to draw firm conclusions. PMID- 27656053 TI - Comparative evaluation of effect of preoperative alprazolam and diclofenac potassium on the success of inferior alveolar, Vazirani-Akinosi, and Gow-Gates techniques for teeth with irreversible pulpitis: Randomized controlled trial. AB - INTRODUCTION: In teeth with irreversible pulpitis, successful local anesthesia is hard to achieve irrespective of the amount of local anesthesia and technique used. Such cases can be managed by concoction of pre-medications like anxiolytics, analgesics and effective local anesthesia. This double-blind, placebo-controlled study was planned to evaluate the effect of oral administration of alprazolam and diclofenac potassium on the success rate of inferior alveolar nerve block (IANB), Gow-Gates (GG) and Vazirani-Akinosi (VA) techniques for the root canal treatment of mandibular molars with irreversible pulpitis. METHOD: 198 emergency patients with symptomatic irreversible pulpitis were randomly divided into three groups as - A, B and C receiving IANB, GG or V-A respectively using 2% lidocaine with 1: 100,000 epinephrine. These groups were sub-divided into sub-groups I and II as control and pre-medication groups. Patients who did not react to the stimulus made by an explorer between the canine and first premolar and showing subjective lip and tongue numbness were included in the study. RESULT: All sub-groups showed statistically significant reduction in VAS score. However sub-groups V and VI (that is GG with and without pre medication respectively) showed best improvement in initial severe pain in mandibular molars with irreversible pulpitis. Moreover, all pre-medication sub groups showed better pain control compared to respective control groups. CONCLUSION: It was concluded that use of pre-medications in the form of combination of anxiolytics and analgesics improves the success rate of local anesthesia in teeth with irreversible pulpitis. Use of anxiolytics eases the patient in endodontic emergencies. Also use of GG along with pre-medication is the best method for effective pain management of acute pain in irreversible pulpitis. PMID- 27656052 TI - Sleep bruxism: Current knowledge and contemporary management. AB - Bruxism is defined as the repetitive jaw muscle activity characterized by the clenching or grinding of teeth. It can be categorized into awake and sleep bruxism (SB). Frequent SB occurs in about 13% of adults. The exact etiology of SB is still unknown and probably multifactorial in nature. Current literature suggests that SB is regulated centrally (pathophysiological and psychosocial factors) and not peripherally (morphological factors). Cited consequences of SB include temporomandibular disorders, headaches, tooth wear/fracture, implant, and other restoration failure. Chairside recognition of SB involves the use of subjective reports, clinical examinations, and trial oral splints. Definitive diagnosis of SB can only be achieved using electrophysiological tools. Pharmacological, psychological, and dental strategies had been employed to manage SB. There is at present, no effective treatment that "cures" or "stops" SB permanently. Management is usually directed toward tooth/restoration protection, reduction of bruxism activity, and pain relief. PMID- 27656054 TI - Effect of apical clearing technique on the treatment outcome of teeth with asymptomatic apical periodontitis: A randomized clinical trial. AB - AIM: This study aims to compare the periapical healing of teeth with asymptomatic apical periodontitis treated either by conventional apical preparation (CAP) or apical clearing technique (ACT). MATERIALS AND METHODS: Twenty subjects with bilateral nonvital similar teeth exhibiting comparable periapical index (PAI) score were enrolled and randomly allocated. Group I (CAP, n = 20): Apical preparation three sizes greater (master apical file [MAF]) than the first binding file at the established working length. Group II (ACT, n = 20): Apical preparation three sizes greater than the MAF that was followed by dry reaming. Root canal therapy was accomplished in single-visit for all the teeth. They were pursued radiographically at 3, 6, 9 and 12 months. Pre- and post-treatment PAI scores were compared. To ascertain the proportion of healed teeth between the two groups, McNemar Chi-square test was applied. RESULTS: At 3, 6, and 9 months' time interval the proportion of healed teeth for Group II (ACT) was greater in comparison to Group I (CAP) (P < 0.05). However, at 12 months follow-up period this difference was not significant (P = 0.08). CONCLUSION: ACT enhanced the healing kinetics. However, the long-term (12 months) radiographic outcome was similar for either technique. PMID- 27656055 TI - Comparative evaluation of the accuracy of two electronic apex locators in determining the working length in teeth with simulated apical root resorption: An in vitro study. AB - INTRODUCTION: Accurate determination of working length (WL) is a critical factor for endodontic success. This is commonly achieved using an apex locator which is influenced by the presence or absence of the apical constriction. Hence, this study was done to compare the accuracy of two generations of apex locators in teeth with simulated apical root resorption. MATERIALS AND METHODS: Forty maxillary central incisors were selected and after access preparation, were embedded in an alginate mold. On achieving partial set, teeth were removed, and a 45 degrees oblique cut was made at the apex. The teeth were replanted and stabilized in the mold, and WL was determined using two generations of apex locators (Raypex 5 and Apex NRG XFR). Actual length of teeth (control) was determined by visual method. STATISTICAL ANALYSIS: Results were subjected to statistical analysis using the paired t-test. RESULTS: Raypex 5 and Apex NRG was accurate for only 33.75% and 23.75% of samples, respectively. However, with +/ 0.5 mm acceptance limit, they showed an average accuracy of 56.2% and 57.5%, respectively. There was no significant difference in the accuracy between the two apex locators. CONCLUSION: Neither of the two apex locators were 100% accurate in determining the WL. PMID- 27656056 TI - Comparative evaluation of the effect of chlorhexidine and Aloe barbadensis Miller (Aloe vera) on dentin stabilization using shear bond testing. AB - INTRODUCTION: The main objective of adhesive dentistry is to create an effective, durable union between the tooth structure and restorative material. However, degradation of adhesive dentine interface remains largely responsible for the relatively short lifetime of tooth colored resin restoration. AIM: The aim of the study is to compare the dentin collagen stabilization property of Chlorhexidine (CHX) and Aloe barbadensis Miller using shear bond strength testing. MATERIALS AND METHODS: Occlusal reduction was done in sixty extracted human mandibular molars to expose the mid coronal dentin and divided into three groups n = 20. Following the surface pretreatment (Group 1 = control, Group 2 = CHX, Group 3 = Aloevera), dentine bonding agent and composite resin were applied and cured. The specimens were then subjected to shear bond strength testing. RESULTS: From the results analyzed, it was noted that there was statistically significant difference between the groups Control and CHX and Control and A. barbadensis Miller (P < 0.05), specifically the values of Control < CHX and Control < A. barbadensis Miller (P < 0.05). However, there was no statistically significant difference between CHX and A. barbadensis Miller (P > 0.05). Hence, the following result for the shear bond strengths to dentin was obtained: Control < CHX ~ A. barbadensis Miller. CONCLUSION: CHX and A. barbadensis Miller, as pretreatment agents of acid demineralized dentin collagen, has no adverse effect on the immediate shear bond strength of a two-step etch and rinse adhesive to dentin. PMID- 27656057 TI - Effect of ProTaper and Reciproc preparation and gutta-percha cone on cold lateral compaction. AB - CONTEXT: The effectiveness of cold lateral compaction depends on the root canal preparation and used gutta-percha cone. AIMS: The aim of this study is to evaluate finger spreader penetration into root canals prepared with ProTaper (PT) or Reciproc (Rec) systems and filled with gutta-percha cones with different tapers. MATERIALS AND METHODS: Twenty-four simulated root canals in resin blocks with 30 degrees curvature were prepared up to PT F2 or Rec R25. They were divided into four experimental groups according to the master gutta-percha cone and preparation (25.02 or F2/PT, and 25.02 or R25/Rec). Cold lateral compaction was performed using a stainless steel finger spreader size B. The set cone-finger spreader-resin block was placed in a universal test machine, and a load up to 1.5 kg was applied on the finger spreader. The final distance between the finger spreader and apical preparation after load application was obtained. For comparison among the groups, data were submitted to ANOVA and Tukey's tests, with a significance level of 5%. RESULTS: Greater finger spreader penetration was observed for 0.02/Rec and 0.02/PT, followed by F2/PT and R25/Rec. CONCLUSION: The use of cones associated with PT and Rec preparations does not allow the finger spreader penetration up to the apical third. PMID- 27656059 TI - Effects of simplified ethanol-wet bonding technique on immediate bond strength with normal versus caries-affected dentin. AB - AIM: The aim of the present study was to evaluate whether the use of simplified ethanol-wet bonding (EWB) technique improved the immediate microtensile bond strength (MUTBS) between resin composite and caries-affected dentin (CAD). MATERIALS AND METHODS: Twenty-four extracted carious human permanent molars were sectioned to expose the carious lesion. The carious dentin was excavated until CAD was exposed. The samples were divided into two groups: water-wet bonding with Adper Scotchbond Multi-Purpose and a simplified EWB (three 100% ethanol applications for 30 s each), followed by application of an experimental hydrophobic primer and restoration. The samples were vertically sectioned to produce 1 mm * 1 mm thick slabs. The normal dentin (ND) slabs and CAD slabs were identified and were subjected to MUTBS evaluation. Slabs from four teeth (two from each group) were evaluated under microscope. Data were analyzed using two way ANOVA and post hoc Holm-Sidak test at P < 0.05. RESULTS: EWB improved the MUTBS in ND but not in CAD group. The dentinal tubules in CAD group showed sclerotic activity with minimal or no hybrid layer. CONCLUSIONS: Simplified ethanol bonding does not improve the bond strength in CAD. PMID- 27656058 TI - Effect of ceramic type, thickness, and time of irradiation on degree of polymerization of dual - cure resin cement. AB - AIM: The aim of the study is to evaluate the effect of ceramic type, thickness, and time of irradiation on degree of polymerization of dual-cure resin cement. MATERIALS AND METHODS: Dual-cure resin cement (SoloCem) was used to prepare disk shaped samples (0.5 mm thick * 5 mm diameter). Study group samples (n = 5) were light-cured for 40, 60, and 80 s through all ceramic leucite-reinforced (Cergo Kiss), lithium disilicate-reinforced (IPS e.max), and monolithic zirconia reinforced (Ziecon) of three thicknesses (2, 3, and 4 mm). Negative control group samples were cured through metal disks and positive control samples were cured without the presence of ceramic. The degree of conversion (DC) was evaluated by Fourier transform infrared spectrometer. The recorded data were subjected to one way analysis of variance, followed by post hoc analysis (Tukey HSD). RESULTS AND CONCLUSION: Greatest light transmission and DC were seen through Cergo Kiss, followed by IPS e.max Press and Ziecon, with insignificant difference between the latter two. The attenuation of light irradiance increased with increasing thickness of ceramic disks, with statistically significant values between 3 and 4 mm. Increasing time of irradiation to cure dual-cure resin cement did not always result in greater degree of polymerization. PMID- 27656060 TI - Effect of diode laser and ultrasonics with and without ethylenediaminetetraacetic acid on smear layer removal from the root canals: A scanning electron microscope study. AB - AIM: To evaluate the effect of diode laser and ultrasonics with and without ethylenediaminetetraacetic acid (EDTA) on the smear layer removal from root canals. MATERIALS AND METHODS: A total of 120 mandibular premolars were decoronated to working the length of 12 mm and prepared with protaper rotary files up to size F3. Group A canals irrigated with 1 ml of 3% sodium hypochlorite (NaOCl) followed by 3 ml of 3% NaOCl. Group B canals irrigated with 1 ml of 17% EDTA followed by 3 ml of 3% NaOCl. Group C canals lased with a diode laser. Group D canals were initially irrigated with 0.8 ml of 17% EDTA the remaining 0.2 ml was used to fill the root canals, and diode laser application was done. Group E canals were irrigated with 1 ml distilled water with passive ultrasonic activation, followed by 3 ml of 3% NaOCl. Group F canals were irrigated with 1 ml EDTA with passive ultrasonic activation, followed by 3 ml of 3% NaOCl. Scanning electron microscope examination of canals was done for remaining smear layer at coronal middle and apical third levels. RESULTS: Ultrasonics with EDTA had the least smear layer scores. CONCLUSION: Diode laser alone performed significantly better than ultrasonics. PMID- 27656061 TI - Effect of bleaching agents having a neutral pH on the surface of mineral trioxide aggregate using electron microscopy and energy dispersive X-ray microanalysis. AB - AIM: To investigate the effect of bleaching agents having a neutral pH on the surface of mineral trioxide aggregate (MTA) used as a coronal seal material for nonvital bleaching, beneath the bleaching agent, with the help of energy dispersive X-ray microanalysis and scanning electron microscopy (SEM). MATERIALS AND METHODS: Six samples of plastic tubes filled with white MTA (Angelus white) were kept in 100% humidity for 21 days. Each sample was divided into 2 and made into 12 samples. These were then divided into three groups. Group A was exposed to Opalescence Boost 40% hydrogen peroxide (HP) (Ultradent). Group B to Opalescence 10% carbamide peroxide (Ultradent) and Group C (control group) not exposed to any bleaching agent. After recommended period of exposure to bleaching agents according to manufacturers' instructions, the samples were observed under SEM with an energy dispersive X-ray microanalysis system (JSM-6380 LA). RESULTS: There were no relevant changes in color and no statistically significant surface structure changes of the MTA in both the experimental groups. CONCLUSION: The present findings suggest that even high concentration HP containing bleaching agents with neutral pH can be used on the surface of MTA without causing structural changes. The superior sealing ability of MTA and the high alkalinity would prevent cervical resorption postbleaching. PMID- 27656062 TI - A comparative evaluation of the increase in root canal surface area and canal transportation in curved root canals by three rotary systems: A cone-beam computed tomographic study. AB - AIM: The aim of this study was to measure the increase in root canal surface area and canal transportation after biomechanical preparation at 1, 3, and 5 mm short of the apex with three different rotary systems in both continuous rotary and reciprocating rotary motions. MATERIALS AND METHODS: Sixty freshly extracted human mandibular molars with mesial root canal curvatures between 20 degrees and 30 degrees were included in the study. Teeth were randomly distributed into three groups (n = 20). Biomechanical preparations were done in all the mesial canals. In Group 1, instrumentation was done with ProTaper universal rotary files, Group 2, with K3XF rotary files, and Group 3, with LSX rotary files. Each group was further subdivided into subgroups A and B (n = 10) where instrumentation was done by continuous rotary and reciprocating rotary techniques, respectively. Increase in root canal surface area and canal transportation was measured using the preoperative and postoperative cone-beam computed tomography scans. STATISTICAL ANALYSIS: The data were analyzed by one way ANOVA followed by Tukey pairwise multiple comparison tests. RESULTS: Increase in root canal surface area was significantly more (P < 0.05) in ProTaper and K3XF groups when compared to LSX group. Canal transportation was significantly more (P < 0.05) in ProTaper group when compared to K3XF and LSX groups. There was no significant difference (P > 0.05) in increase of root canal surface area and canal transportation between continuous rotary and reciprocating rotary techniques for ProTaper Universal, K3XF and LSX groups. CONCLUSION: LSX rotary system showed minimal increase of root canal surface area and minimal canal transportation when compared to ProTaper and K3XF rotary systems. PMID- 27656063 TI - Comparative evaluation of canal transportation, centering ability, and remaining dentin thickness between WaveOne and ProTaper rotary by using cone beam computed tomography: An in vitro study. AB - AIMS: To compare the canal transportation, centering ability, and remaining dentin thickness of WaveOne and ProTaper systems using cone beam computed tomography. SUBJECTS AND METHODS: Forty extracted human single-rooted premolars were used in the present study. Preinstrumentation scanning of all teeth was taken; canal curvatures were calculated, and the samples were randomly divided into two groups, with twenty samples in each group; one group was instrumented with WaveOne system and the other group with ProTaper rotary system. Postinstrumentation scans were performed, and the two scans were compared to determine canal transportation, centering ability, and remaining dentin thickness at 3 mm, 6 mm, and 9 mm from the root apex. STATISTICAL ANALYSIS USED: Student's unpaired t-test. RESULTS: Using Student's unpaired t-test, results were as follows: for canal transportation, Group 1 showed significant difference at 3 mm and 6 mm and insignificant difference at 9 mm while Group 2 showed insignificant difference in all the three regions. For centering ability and remaining dentin thickness, Group 1 showed insignificant difference at 3 mm and 9 mm while significant difference at 6 mm was obtained. When comparison of remaining dentin thickness was done at three levels using two groups WaveOne and ProTaper, there was no significant difference between two groups. CONCLUSIONS: (1) WaveOne single reciprocation file system respected better canal anatomy better than ProTaper. (2) Individually, centering ability of WaveOne was better at 3 mm, 6 mm, and 9 mm levels. (3) However, ProTaper individually was better centered at 3 mm (apical third) and 9 mm (coronal 3(rd)) levels than 6 mm level (middle third). PMID- 27656064 TI - Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods. AB - AIM: To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. MATERIALS AND METHODS: Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (CHX), neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, and diode laser. The effect of disinfection methods was assessed by LIVE/DEAD BacLight stain under the confocal laser scanning microscopy to determine the "zone of dead bacteria" (ZDB). Mean values were calculated for ZDB and the difference between groups was established. RESULTS: Penetration of E. faecalis was seen to a depth of >1000 MUm. Viable bacteria were detected with NS irrigation. NaOCl and CHX showed partial ZDB. When the root canals were disinfected with Nd: YAG and diode lasers, no viable bacteria were found. CONCLUSION: E. faecalis has the ability to colonize inside dentinal tubules to a depth of >1000 MUm. In contrast to conventional irrigants, both Nd: YAG and diode lasers were effective in eliminating the vitality of E. faecalis. NS, NaOCl, and CHX showed viable bacteria remaining in dentinal tubules. PMID- 27656065 TI - Cone beam computed tomographic evaluation of two access cavity designs and instrumentation on the thickness of peri-cervical dentin in mandibular anterior teeth. AB - BACKGROUND AND OBJECTIVES: The aim of the study was to determine the effect of two access cavity designs on the peri-cervical dentin thickness before and after instrumentation using cone beam computed tomography (CBCT). MATERIALS AND METHODS: Sixty mandibular anterior teeth were divided into two groups of thirty teeth each: Group I: conventional access cavity preparation, where access was prepared just above the cingulum and Group II: incisal access cavity preparation, where access was prepared in proximity to the incisal edge. CBCT scans were taken preoperatively, following access cavity preparation and post instrumentation. 200 MUm thick slices were obtained 4mm apical and coronal to the cemento-enamel junction. The peri-cervical dentin thickness was calculated on the facial, lingual, mesial, and distal for all the three obtained scans. RESULTS: The analysis showed that access cavity preparation and instrumentation resulted in a significant loss of tooth structure in Group I on all surfaces, but in Group II, there was a significant loss of tooth structure only in the mesial, lingual, and distal surfaces (P < 0.05). CONCLUSION: Incisal access cavity preparation resulted in lesser loss of dentin in the peri-cervical region. PMID- 27656067 TI - Comparison of bond strength of different endodontic sealers to root dentin: An in vitro push-out test. AB - AIM: To compare the bond strength of four different endodontic sealers to root dentin through push-out test design. MATERIALS AND METHODS: Forty single-rooted teeth with completely formed apices were selected. Teeth were decoronated, and working length was determined. Instrumentation and irrigation were performed. The teeth were divided into four groups based upon the sealer used. Group 1: Bioceramic sealer (Endosequence), Group 2: Mineral trioxide aggregate (MTA) based sealer (MTA Fill apex), Group 3: Epoxy resin based sealer (MM-Seal), and Group 4: Dual cure resin-based sealer (Hybrid Root Seal). Manipulation and application of the sealer was done as per the manufacturer instructions. All the teeth were obturated using 6% gutta-percha. After obturation, each tooth was prepared for push-out test with root slices of 2 mm thickness using universal testing machine. RESULTS: The highest bond strength was found in Group 1 (Endosequence) (P < 0.05) compared to other groups. The lowest bond strength was found in Group 2 (MTA Fill apex). Statistical analysis is done by two-way ANOVA and Newman-Keuls multiple post hoc. CONCLUSION: The push-out bond strength of Bioceramic sealer was highest followed by resin-based sealer and lowest bond strength was observed in MTA-based sealer. PMID- 27656066 TI - Effect of dentin on the antimicrobial efficacy of 3% sodium hypochlorite, 2% chlorhexidine, 17% ethylenediaminetetraacetic acid, and 18% etidronic acid on Candida albicans: An in vitro study. AB - AIM: The aim of this study was to evaluate the effect of dentin on the antimicrobial efficacy of 3% sodium hypochlorite, 2% chlorhexidine, 17% EDTA and 18% etidronic acid against C. albicans. METHODOLOGY: Dentin powder was prepared from mandibular first premolar using electrical grinder and sterilized. 3% NaOCl, 2%CHX, 17% EDTA and 18% etidronic acid were tested against C. albicans in the presence and absence of dentin, in eppendorf tubes. Group 1 (presence of dentin): 100ul dentin powder + 100ul C. albicans suspension + 100ul irrigating solution. Group 2 (absence of dentin):- 100ul C. albicans suspension+ 100ul irrigating solution. CONTROL GROUP: - 100ul C. albicans suspension.+ 100ul sterile saline Suspension was thoroughly mixed, submitted for serial dilution upto10-5 after 1 min and colony forming units were counted. RESULTS: In group 2 (without dentin powder), 3% NaOCl and 2% CHX showed the lowest bacterial count compared to group 1 (with dentin powder). Dentin had a significant inhibitory effect on 3% NaOCl (P < 0.001) and 2% CHX (P<0.001). 17% EDTA showed lowest bacterial count in group 1 (with dentin powder) compared to group 2 (without dentin powder). 18% Etidronic acid showed similar bacterial counts in the both the groups. No reduction was observed in the control group. CONCLUSION: NaOCl & EDTA showed measurable antimicrobial effect even in the presence of dentin which can be promising in the reduction of C. albicans in root canal therapy. PMID- 27656068 TI - Capacity of a hydroxyapatite-lysozyme combination against Streptococcus mutans for the treatment of dentinal caries. AB - BACKGROUND: One current strategy for the treatment of carious lesions is the use of biomaterials with antimicrobial activity. AIMS: The aim of this study was to evaluate a combination of hydroxyapatite and lysozyme for the treatment of dentinal caries by measuring Streptococcus mutans counts before carious tissue sealing, and 24 h, 1 month, and 6 months after treatment. MATERIALS AND METHODS: Forty permanent third molars were selected, and flat dentin surfaces were prepared. The teeth were exposed to a cariogenic challenge with S. mutans. After challenge, the dentinal caries were collected from five specimens. The remaining specimens were treated with a mixture of hydroxyapatite and lysozyme in sodium laureth sulfate and sealed with composite resin. S. mutans counts were obtained 24 h, 1 month, and 6 months after sealing. STATISTICAL ANALYSIS: The results were evaluated by descriptive statistics and Wilcoxon signed-rank test. RESULTS: a significant reduction in S. mutans (CFU/mL) was observed in dentinal lesions 1 month after treatment with hydroxyapatite/lysozyme in sodium laureth sulfate (P = 0.0254). Comparison of S. mutans counts obtained 24 h, 1 month, and 6 months after treatment revealed reductions only at the 1-month time point (P = 0.0318). CONCLUSIONS: the combination of hydroxyapatite and lysozyme may be an alternative for reducing the S. mutans burden in dentinal caries. PMID- 27656069 TI - Overall pattern of publication in Journal of Conservative Dentistry. AB - BACKGROUND: The Journal of Conservative Dentistry (JCD) has been online since 2008. MATERIALS AND METHODS: This paper reviews the publication in this journal over a 5-year period (2011-2015). It assesses the types of articles published, coverage of various types of subjects of endodontics, and conservative dentistry in the journal and explores the authorship patterns in the publication and citation of the journal over this period. RESULTS AND CONCLUSION: JCD has delivered broad-based, balanced coverage of endodontics and conservative dentistry between 2011 and 2015, with contributions from all over India, as well as abroad. Although a maximum number of articles were from India, the publications from other countries are also on an increase. Thus, the widespread coverage of this journal suggests that JCD has begun to represent the global face of the Indian Association of Conservative Dentistry and Endodontics. PMID- 27656071 TI - Centering and transportation: in vitro evaluation of continuous and reciprocating systems in curved root canals. AB - CONTEXT: One of the goals of endodontic therapy is the shaping and cleaning of the root canal system. In recent years, there has been multiple systems instrumentation, and changes in their dynamics are central to maintain the original shape of the canal after preparation. AIMS: The aim of this study was to evaluate centering and transportation in curved root canals after using ProTaper((r)) and MTwo((r)) in continuous rotation, Reciproc((r)) in reciprocating motion, and a step-down manual instrumentation technique. SETTINGS AND DESIGN: Mesiobuccal roots of human extracted the first and second maxillary molars were selected and the canals (n = 60) were divided into four groups according to the preparation techniques: PT-ProTaper((r)); MT-MTwo((r)); RE Reciproc((r)); MI-manual instrumentation. SUBJECTS AND METHODS: The final apical diameter was standardized to a size 25. Centering and transportation were evaluated by cone-beam computed tomography and Adobe Photoshop 8.0 software. STATISTICAL ANALYSIS USED: The data were statistically analyzed by ANOVA and Tukey post hoc. RESULTS: Results of transportation showed no statistical differences (P > 0.05) between groups, and significantly, difference (P < 0.05) between ProTaper((r)) and Reciproc((r)) was found when evaluating centering ability in the apical third. CONCLUSIONS: We concluded that there were no differences in transportation between the evaluated systems for the preparation of curved root canals with an apical instrumentation diameter of #25. For centering ability, in the apical third, ProTaper((r)) presented worst behavior when compared to Reciproc((r)). PMID- 27656070 TI - Effect of chitosan-ethylenediamine tetraacetic acid on Enterococcus faecalis dentinal biofilm and smear layer removal. AB - OBJECTIVE: The objective of the study was to evaluate the effectiveness of chitosan and chitosan-ethylenediamine tetraacetic acid (EDTA) (3:1,1:1,1:3) in comparison with 5.2% sodium hypochlorite (NaOCl) in disinfecting Enterococcus faecalis biofilm on root canal dentin and in the removal of smear layer with minimal erosion. MATERIALS AND METHODS: Seventy single-rooted extracted human mandibular premolars (n = 70) were selected for the study. Forty tooth samples were biomechanically prepared, vertically sectioned, and sterilized by autoclaving. The tooth sections were artificially infected with E. faecalis (ATCC 29212 [n = 35] and clinical isolate [SBEF2, n = 35]) to form mature dentinal biofilm in vitro. The tooth samples were treated with the test solutions: chitosan and chitosan-EDTA (3:1, 1:1, 1:3), and the killing time was determined. The smear layer removal ability of the test solutions (Group A: chitosan-EDTA [1:1], Group B: EDTA, Group C: control) (n = 10 tooth/group) was assessed. RESULTS: Chitosan and chitosan-EDTA (3:1, 1:1, 1:3) exhibited antibacterial activity against both the strains of E. faecalis. Chitosan and chitosan-EDTA caused 3 log reduction in the viable count of the sessile cells of E. faecalis at 15 min while 5.2% NaOCl exhibited 99.98% inhibition at 15 min. Chitosan-EDTA (1:1) was found to be effective in removing the smear layer and showed lesser erosion than EDTA at the coronal and middle portions. CONCLUSION: Chitosan-EDTA (1:1) is a potential root canal irrigant that performs a dual role - root canal disinfection and smear layer removal. PMID- 27656072 TI - Leaching of monomers from bulk-fill composites: An in vitro study. AB - AIM AND OBJECTIVES: To evaluate the elution of bisphenol A-glycidyl methacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) from two bulk-fill composites at different polymerization times, for different storage periods when cured with quartz-tungsten-halogen (QTH) curing unit. MATERIALS AND METHODS: Tetric N-Ceram bulk fill and EverX Posterior were analyzed using high-performance liquid chromatography unit. Totally, 68 samples were prepared, two groups (n = 17) from both the composites, one for each tested polymerization time. Each sample was cured with a QTH curing unit, using soft-start curing technique and stored in 2 ml of ethanol for 24 h. Storage medium was renewed and then stored again for 1 week. Data acquired were statistically analyzed. RESULTS: The elution of BisGMA was significantly higher from Tetric N-Ceram bulk fill and BisGMA and TEGDMA from EverX Posterior composite at the end of 24 h, irrespective of the curing time. In EverX Posterior, a higher amount of TEGDMA was eluted at the end of 24 h, while at the end of 1 week, significantly higher amount of BisGMA was released. CONCLUSION: A significant amount of the release of BisGMA as well as TEGDMA was seen from both the composites when stored for different time intervals. PMID- 27656073 TI - Dens in dente: A minimally invasive nonsurgical approach! AB - Dens invaginatus, also known as dens in dente, is a rare anomaly affecting human dentition. The condition results in invagination of an amelodental structure within the pulp. This case report discusses the current management protocol of dens invaginatus using a minimally invasive and nonsurgical treatment option. As with most conditions, early diagnosis and preventive measures help minimize complications in dens invaginatus cases. PMID- 27656074 TI - The stamp technique for direct Class II composite restorations: A case series. AB - BACKGROUND: "Stamp" technique is a new method for placing large composite restorations with accurate occlusal topography. It was introduced mainly to restore Class I cavities and erosively damaged teeth. This technique is indicated when the preoperative anatomy of the tooth is intact and not lost due to the carious lesion. A precise tooth-like filling an accurate functional occlusion is obtained when the stamp technique is applied. However, using this technique to restore Class II cavities is not established yet. AIM: To introduce modifications of the stamp technique that make it applicable to restore Class II composite restorations. MATERIALS AND METHODS: The traditional materials and tools used for direct composite restorations are needed with no additional instruments. Clinical illustrations and step-by-step description are provided in this paper. RESULTS AND CONCLUSION: Using the stamp technique to restore Class II cavities is achievable, simple and practical, and result in a very accurate anatomical restoration. PMID- 27656075 TI - Hip structure analysis by DXA of teriparatide treatment: A 24-month follow-up clinical study. AB - OBJECTIVE: The objective of this study was to perform a hip structure analysis (HSA) of teriparatide (TPTD) treatment in women with postmenopausal osteoporosis. METHODS: The study included 96 patients with postmenopausal osteoporosis and received 20 MUg TPTD daily. HSA was performed by dual-energy X-ray absorptiometry. RESULTS: The percent changes from baseline for the cross sectional moment of inertia, section modulus, buckling ratio, and femoral strength index based on HSA results were 9.8% (p < 0.01), 10.7%, 3.3%, and 14.9% (p < 0.01), respectively, at 24 months. CONCLUSION: Based on the HSA results obtained with DXA, TPTD was effective for hip structures. PMID- 27656076 TI - The role of lasers in the treatment of peri-implant diseases: A review. AB - We reviewed the indexed literature regarding the efficacy of laser therapy in the treatment of peri-implantitis (PI). Databases were searched using combinations of the following keywords: peri-implantitis, bone loss, photodynamic therapy, laser, and light-activated disinfection. Titles and abstracts of publications from these search results were screened to determine which studies fulfilled the eligibility criteria. Full texts of relevant studies were read and independently assessed against the eligibility criteria. The resulting 28 studies described the role of lasers in the treatment of PI. The erbium:yttrium-aluminum-garnet laser can be used to sterilize implant surfaces without damaging them. Likewise, the carbon dioxide laser can disinfect implant surfaces and enhance the bone-to-implant contact around previously infected sites. Photodynamic therapy exhibits high target specificity and can destroy pathogens associated with the etiology of PI. Laser therapy can significantly reduce levels of clinical markers of peri-implant tissue inflammation (i.e., bleeding upon probing and clinical attachment loss) without jeopardizing the integrity of the implant or alveolar bone. In conclusion, laser therapy as an adjunct to conventional mechanical debridement therapy can be used effectively for the treatment of PI. PMID- 27656077 TI - Evaluation of bone regenerative capacity in rats claverial bone defect using platelet rich fibrin with and without beta tri calcium phosphate bone graft material. AB - AIM: To compare bone regeneration in noncritical rat calvarial bone defects filled with platelet-rich fibrin (PRF), alone or combined with beta-tricalcium phosphate (beta-TCP), using micro-computed tomographic (MCT) evaluation. ANIMALS AND METHODS: Two calvarial bone defects were created in each of 45 male Sprague Dawley rats (age: 20-22 weeks, weight: 350-450 g), using a dental trephine with an external diameter of 3 mm. The 90 defects were randomly allocated among three groups, each containing 30 unilateral defects in a total of 30 rats. Defects in the control group were allowed to heal spontaneously. Defects in the PRF group received PRF alone. Defects in the PRF/beta-TCP group received PRF mixed with beta-TCP in a 50?50 percentage. Nine animals (three per group) were killed after 1, 2, 3, 4, and 6 postoperative weeks, and 18 calvarial defects from each period were analyzed for new bone formation and bone mineral density using MCT. Results were compared by a one-way Analysis of Variance with the POST HOC Least Significant Difference test. RESULTS: The volume and mineral density of bone formed in the control group were significantly different from those of the other two groups. Greater bone regeneration was observed in defects receiving PRF with beta-TCP compared to defects receiving PRF alone in the first 2 weeks (P < 0.001). However, differences in the volume and density of newly formed bone between the PRF and PRF/beta-TCP groups were not significant at 3, 4, and 6 postoperative weeks (P > 0.005). CONCLUSION: The addition of beta-TCP to PRF significantly improved bone regeneration in the first 2 weeks after surgery. Although the differences between results with and without the addition of beta TCP to PRF were statistically insignificant from weeks 3 to 6, it was nevertheless apparent that the group receiving the combination showed better results. We suggest a synergistic mechanism for this effect. PMID- 27656078 TI - Self-perceived halitosis and related factors among adults residing in Riyadh, Saudi Arabia. A cross sectional study. AB - OBJECTIVES: This cross-sectional observational study was conducted to determine the prevalence of self-perceived halitosis among adults in Riyadh, Saudi Arabia and to assess the relation of halitosis with some socio-demographic factors, oral habits and health practices. MATERIALS AND METHODS: A questionnaire was distributed to randomly selected subjects including senior high school students, college students and employees working in governmental offices. High schools and governmental offices were selected using systematic random sampling from each of the main five regions of Riyadh. The college students were selected from the major universities in Riyadh. One hundred questionnaires were randomly distributed in each of the 15 locations for males and 15 for females (5 schools, 5 universities and 5 governmental offices for each gender) giving a total of 3000 questionnaires. RESULTS: The prevalence of self-perceived halitosis was 22.8% among the participants. The majority of the subjects with self-perceived halitosis experienced bad breath on waking up (83.5%). Nearly half of the sample with self-perceived halitosis was told by others that they had bad breath, 25.8% visited a doctor regarding that, 23.8% received treatment for their bad breath and 54.1% made trials to control their problem by using some aids. Self-perceived halitosis was found to be more prevalent among males compared to females (P < 0.000), whereas, no statistically significant differences were found among the different age groups (P = 0.317). A statistically significant relationship was found between self-perceived halitosis and times of mouth cleaning, use of tooth brush, use of tooth paste, tongue cleaning (P < 0.000), and the use of dental floss (P = 0.004). A statistically significant relationship was also found between self-perceived halitosis and shisha (P < 0.000) and cigarette smoking (P = 0.045). CONCLUSION: The prevalence of self-perceived halitosis among the population in Riyadh is within the range reported in other countries. Self perceived halitosis is related to gender, inadequate oral hygiene practices and cigarettes and shisha smoking however, it is not related to age. PMID- 27656079 TI - Association between salivary sialic acid and periodontal health status among smokers. AB - BACKGROUND: Smoking is an environmental risk factor causing poor dental health. Sialic acid is a salivary marker of oxidative stress for research of periodontal diseases. AIMS: To identify diagnostic sialic acid fraction and its scavenger effect for periodontal diseases among smokers and periodental health status. SUBJECT AND METHOD: This study carried out in the Khanzad specialized dental center - Erbil city. The study population is composed of 62 convenient samples. A structured interview questionnaire form was used to collect data about socio demographic properties and smoking history. Clinical measurements were carried out to measure periodontal health status. Un-stimulated whole saliva samples were collected for measuring sialic acid fractions. Statistical package for social science (SPSS, version 18), was used for analysis and odds ratio. RESULTS: Risk of smoking increased significantly in young to mid ages, which included most of the current smokers, with periodontal diseases, and high total free sialic acid. Risk of periodontitis and teeth missing increased significantly by long duration of smoking, bad tooth brushing, and poor eating habits. Risk of teeth mobility and loss decreased significantly by early smoking cessation and low income. High levels of free sialic acid correlated significantly in current smokers with medium and deep pocket depth. CONCLUSION: Salivary free sialic acid may be used as a diagnostic oxidative stress biomarker for periodontal diseases among young current smokers. Cumulative destructive effect of long duration of smoking on the periodontum can be controlled by smoking cessation, good oral hygiene and diet habit in early old ages. PMID- 27656080 TI - The knowledge, attitude and practices of male sports participants to sports related dental trauma in Khobar and Dammam, Saudi Arabia - A pilot survey. AB - The risk of dental trauma may increase during sports participation. The purpose of this study was to evaluate the knowledge, attitude, and practices of sports participants concerning sports-related dental trauma and associated emergency/preventive practices. The study included 124 male subjects over 18 years of age participating in contact and non-contact sports in three clubs in the Eastern Province, Saudi Arabia. A questionnaire was used to assess past experience of dental trauma related to sports in addition to the use of a mouth guard and knowledge of related emergency procedures. Outcomes were compared between individuals practicing direct and non-direct contact sports. One third of the participants had experienced dental trauma while playing sports, mostly crown fracture, mobility, and avulsion. Their knowledge of first aid and emergency procedures was inadequate. A significantly higher proportion of non-direct contact sport participants sought the help of a dentist for themselves or others (P = 0.04 and 0.003, respectively). Only 33.9% used mouth guards, with higher odds of mouth guard use associated with participating in direct contact sports and believing a tooth can be lost during sports practice (odds ratio = 5.59 and 5.37, respectively). Educational programs are needed to increase the awareness in sports participants of the risk of dental trauma during sports participation, to improve their knowledge of first aid procedures, and to increase the use of mouth guards. PMID- 27656082 TI - A first experience with digital complete overdentures. AB - The development of computer-aided design/computer-aided manufacturing systems for dentistry in the 1980s resulted in the successful fabrication of crowns, fixed dental prostheses, and superstructures for both natural teeth and dental implants. Today, this technology is available for constructing digitally designed and milled, completely removable dental prostheses. The procedure uses clinical and laboratory protocols that allow fabrication of completely removable prostheses within two clinical appointments. The aim of this clinical report is to present the author's first experience with digital complete overdentures, the practicality of this technology, and patient feedback. Compared with conventional overdentures, the fit of the digital prostheses was improved because the cameo and flanges of the prostheses were nicely shaped and rolled, and this enhanced their stability and retention. Occlusion was also excellent. However, aesthetics in terms of the alignment, shape, and size of the maxillary overdenture teeth were inacceptable. Despite some of the drawbacks identified in our study, the use of removable digital dentures does provide excellent adaptation of the denture base and requires fewer clinic visits. We anticipate that the unsatisfactory aesthetic outcomes presented in this report can be corrected with more experience. We also believe that acquiring an in-house scanning machine would be beneficial. We highly recommend including this technique in dental school curriculums at both the undergraduate and graduate levels in order to keep students and residents up to date on the latest technology available. PMID- 27656081 TI - Children's ages and reasons for receiving their first dental visit in a Saudi community. AB - OBJECTIVE: Epidemiological studies conducted in different parts of the world have revealed the postponement of first dental visits and an increased prevalence of early childhood caries in general populations in developed and developing countries. This study aimed to assess the average age of and most common reasons for first dental visits in children attending governmental and private dental clinics in Riyadh, Saudi Arabia. SUBJECTS AND METHODS: Data were collected retrospectively from the dental records of new pediatric patients attending a governmental institute (College of Dentistry, Department of Pediatric Dentistry and Orthodontics, King Saud University) and a private clinic (the investigator's private practice) in Riyadh. Only children attending their first dental visits with no previous dental experience were included in the study. Descriptive statistics, cross-tabulation analysis, and chi-squared test were done. The significance level was set at P ? 0.05. RESULTS: Initial dental visitation occurred at 1-3 years in 32.2% of children, 3-5 years in 52.9% of children, at >5 years in 14% of children. Pain was the dominant reason (71.5%) for first dental visits. Dental check-up was the main reason for 27.3% of dental visits, and fluoride application was the main reason for 20.5% of visits. Emergency cases accounted for 44.7% of first dental visits during the study period. Most (68%) children were medically fit, and 67.2% behaved positively during their first dental procedures. CONCLUSIONS: Parental compliance with the standard age for initial dental visitation recommended by the major dental academies is lacking. PMID- 27656083 TI - Maternal age at maturation underpins contrasting behavior in offspring. AB - In species where parental care occurs primarily via the provisioning of eggs, older females tend to produce larger offspring that have better fitness prospects. Remarkably however, a relationship between age of mother and fitness of offspring has also been reported independently of effects on offspring size suggesting that there may be other factors at play. Here, using experimental matings between wild Atlantic salmon that differed in their age at sexual maturation, we demonstrate distinct size-independent variation in the behavior of their offspring that was related to the maturation age of the mother (but not the father). We found that when juvenile salmon were competing for feeding territories, offspring of early-maturing mothers were more aggressive than those of late-maturing mothers, but were out-competed for food by them. This is the first demonstration of a link between natural variation in parental age at maturation and variation in offspring behavior. PMID- 27656084 TI - Imperfect past and present progressive: beak color reflects early-life and adult exposure to antigen. AB - Secondary sexual traits may convey information about individual condition. We assessed the capacity for immune challenge with lipopolysaccharide (LPS) or keyhole limpet hemocyanin (KLH) during the prenatal and early postnatal stages to impact beak color development and expression in captive zebra finches. In addition, we tested whether adult immune challenge impacted beak color, and if early-life experience was influential. Immune challenge with KLH early in life slowed development of red beak coloration, and males challenged with KLH as nestlings had reduced red coloration as adults. Following adult KLH challenge, males exhibited a decline in beak redness. Birds challenged with KLH during development produced more anti-KLH antibodies after adult challenge. There was a significant interaction between young treatment and anti-KLH antibody production; for males not challenged with KLH early in life, individuals that mounted a weaker antibody response lost more red coloration after challenge than males mounting a stronger antibody response. Based on models of avian vision, these differences in beak coloration should be detectable to the finches. In contrast to previous studies, we found no effect of early-life or adult challenge with LPS on any aspects of beak coloration. These results provide evidence that beak color reflects developmental and current conditions, and that the signal is linked to critical physiological processes. PMID- 27656085 TI - Not leaving home: grandmothers and male dispersal in a duolocal human society. AB - Models suggest that dispersal patterns will influence age- and sex-dependent helping behavior in social species. Duolocal social systems (where neither sex disperses and mating is outside the group) are predicted to be associated with mothers favoring sons over daughters (because the latter are in reproductive competition with each other). Other models predict daughter-biased investment when benefits of wealth to sons are less than daughters. Here, we test whether sex-biased investment is occurring in the duolocal Mosuo of southwestern China. Using demographic and observational data from Mosuo, we show support for both hypotheses, in that 1) males are more likely to disperse from their natal household if their mother dies, but females are not; 2) a large number of brothers increases the likelihood that both females and males disperse, whereas a large number of sisters only increases female dispersal; 3) mothers help daughters reproduce earlier and reduce death risk of daughter's children, but not sons or sons' children; 4) data on multiple paternity show that female reproductive success does not suffer from multiple partners, and in males multiple mates are associated with higher reproductive success, indicating that mothers can benefit from investing in their sons' mating effort; and 5) gift decisions reveal similar kin effects to those shown in the demographic data, with mothers helping adult daughters and adult sons equally, but helping only her daughter's children, not her son's children. Mosuo mothers may invest resources for parental investment in their daughters and their offspring, while investing in their sons mating effort. PMID- 27656086 TI - Sexually selected sentinels? Evidence of a role for intrasexual competition in sentinel behavior. AB - Although the evolutionary mechanisms that favor investment in cooperative behaviors have long been a focus of research, comparatively few studies have considered the role that sexual selection may play. For example, evolutionary explanations for sentinel behavior (where 1 individual assumes an elevated position and scans the surroundings while other group members forage nearby) have traditionally focused on the inclusive fitness benefits arising from its effects on predation risk, while its potential role in defense against intrasexual competitors remains largely unexplored. Here, we provide experimental evidence of a role for sentinel behavior in intrasexual competition, in a cooperatively breeding songbird, the white-browed sparrow weaver (Plocepasser mahali). First, dominant males sentinel substantially more than other group members (even when controlling for variation in age and body condition), consistent with a role for sentineling in intrasexual competition for mates and/or territory. Second, experimental playback of an unfamiliar male's solo song elicited a marked increase in sentineling by the dominant male, and the vocal response to the playback also positively predicted his sentinel effort following the simulated intrusion. A second experiment also suggests that sentineling may facilitate mounting rapid anti-intruder responses, as responses to intruder-playback occurred significantly earlier when the dominant male was sentineling rather than foraging at playback onset. Together, our findings provide rare support for the hypothesis that sentinel behavior plays a role in intrasexual competition, and so highlight the potential for sexually selected direct benefits to shape its expression in this and other social vertebrates. PMID- 27656087 TI - Dazzle camouflage, target tracking, and the confusion effect. AB - The influence of coloration on the ecology and evolution of moving animals in groups is poorly understood. Animals in groups benefit from the "confusion effect," where predator attack success is reduced with increasing group size or density. This is thought to be due to a sensory bottleneck: an increase in the difficulty of tracking one object among many. Motion dazzle camouflage has been hypothesized to disrupt accurate perception of the trajectory or speed of an object or animal. The current study investigates the suggestion that dazzle camouflage may enhance the confusion effect. Utilizing a computer game style experiment with human predators, we found that when moving in groups, targets with stripes parallel to the targets' direction of motion interact with the confusion effect to a greater degree, and are harder to track, than those with more conventional background matching patterns. The findings represent empirical evidence that some high-contrast patterns may benefit animals in groups. The results also highlight the possibility that orientation and turning may be more relevant in the mechanisms of dazzle camouflage than previously recognized. PMID- 27656088 TI - The Role of Rigidity in Adaptive and Maladaptive Families Assessed by FACES IV: The Points of View of Adolescents. AB - Previous studies using Olson's Circumplex Model and FACES IV, the self-report assessing family functioning, did not clarify the role of rigidity, a dimension of this model. Rigidity emerged as ambiguous: it was considered either as a functional or as a dysfunctional dimension. Building upon the results of previous studies, we provided a contribution intended to disambiguate the role of rigidity considering adolescents' perceptions and using a non-a priori classification analysis. 320 Italian adolescents (13-21 years) participated in this study and responded to a questionnaire containing scales of the study variables. A latent class analysis was performed to identify the association of rigidity with the other dimensions of Olson's model and with indicators of adaptive family functioning in adolescence: parental monitoring and family satisfaction. We found six clusters corresponding to family typologies and having different levels of functioning. Rigidity emerged as adaptive in the typologies named rigidly balanced and flexibly oscillating; it was associated with positive dimensions of family functioning, i.e. flexibility, cohesion, parental monitoring, and high levels of family satisfaction. Differently, when rigidity was associated with disengagement, low cohesion and flexibility, and lack of parental supervision, emerged as maladaptive. This was the case of two typologies: the rigidly disengaged and the chaotically disengaged. Adolescents of these families reported the lowest levels of satisfaction. In the two last typologies, the flexibly chaotic and the cohesively disorganized, rigidity indicated a mid-range functionality as these families were characterized by emotional connectedness but lack of containment. Clinical implications are discussed. PMID- 27656090 TI - Design and realization of transparent solar modules based on luminescent solar concentrators integrating nanostructured photonic crystals. AB - Herein, we present a prototype of a photovoltaic module that combines a luminescent solar concentrator integrating one-dimensional photonic crystals and in-plane CuInGaSe2 (CIGS) solar cells. Highly uniform and wide-area nanostructured multilayers with photonic crystal properties were deposited by a cost-efficient and scalable liquid processing amenable to large-scale fabrication. Their role is to both maximize light absorption in the targeted spectral range, determined by the fluorophore employed, and minimize losses caused by emission at angles within the escape cone of the planar concentrator. From a structural perspective, the porous nature of the layers facilitates the integration with the thermoplastic polymers typically used to encapsulate and seal these modules. Judicious design of the module geometry, as well as of the optical properties of the dielectric mirrors employed, allows optimizing light guiding and hence photovoltaic performance while preserving a great deal of transparency. Optimized in-plane designs like the one herein proposed are of relevance for building integrated photovoltaics, as ease of fabrication, long term stability and improved performance are simultaneously achieved. (c) 2015 The Authors. Progress in Photovoltaics: Research and Applications published by John Wiley & Sons Ltd. PMID- 27656089 TI - Influence of Child Factors on Health-Care Professionals' Recognition of Common Childhood Mental-Health Problems. AB - Early recognition of childhood mental-health problems can help minimise long-term negative outcomes. Recognition of mental-health problems, needed for referral and diagnostic evaluation, is largely dependent on health-care professionals' (HCPs) judgement of symptoms presented by the child. This study aimed to establish whether HCPs recognition of mental-health problems varies as a function of three child-related factors (type of problem, number of symptoms, and demographic characteristics). In an online survey, HCPs (n = 431) evaluated a series of vignettes describing children with symptoms of mental-health problems. Vignettes varied by problem type (Attention-Deficit/Hyperactivity Disorder (ADHD), Generalised Anxiety Disorder (GAD), Autism Spectrum Disorder (ASD), Conduct Disorder (CD) and Major Depressive Disorder), number of symptoms presented (few and many), and child demographic characteristics (ethnicity, gender, age and socio-economic status (SES)). Results show that recognition of mental-health problems varies by problem type, with ADHD best recognised and GAD worst. Furthermore, recognition varies by the number of symptoms presented. Unexpectedly, a child's gender, ethnicity and family SES did not influence likelihood of problem recognition. These results are the first to reveal differences in HCPs' recognition of various common childhood mental-health problems. HCPs in practice should be advised about poor recognition of GAD, and superior recognition of ADHD, if recognition of all childhood mental-health problems is to be equal. PMID- 27656091 TI - Castor Oil: Properties, Uses, and Optimization of Processing Parameters in Commercial Production. AB - Castor oil, produced from castor beans, has long been considered to be of important commercial value primarily for the manufacturing of soaps, lubricants, and coatings, among others. Global castor oil production is concentrated primarily in a small geographic region of Gujarat in Western India. This region is favorable due to its labor-intensive cultivation method and subtropical climate conditions. Entrepreneurs and castor processors in the United States and South America also cultivate castor beans but are faced with the challenge of achieving high castor oil production efficiency, as well as obtaining the desired oil quality. In this manuscript, we provide a detailed analysis of novel processing methods involved in castor oil production. We discuss novel processing methods by explaining specific processing parameters involved in castor oil production. PMID- 27656092 TI - Echocardiographic Assessment of Cardiac Changes During Normal Pregnancy Among Nigerians. AB - BACKGROUND: Pregnancy is a physiological process associated with an increased hemodynamic load and cardiac structural remodeling. Limited echocardiographic information exists on cardiac chambers, left ventricular (LV) systolic and diastolic functions, and LV mass during trimesters of normal pregnancy among African women. MATERIALS AND METHODS: Echocardiography was done at the beginning of the second trimester, beginning of the third trimester, and middle of the third trimester for 100 normal pregnant women and at one visit for age-matched 100 nonpregnant women. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 17 software. Analysis of variance was used to compare within trimesters, and a P value of <0.05 was considered significant. RESULTS: The mean (SD) ages of the patients and controls were 28.20 (+/-5.91) and 28.35 (+/-6.06) years, respectively (age range = 19-44 years, P = 0.86). Cardiac chambers, LV systolic function, and LV mass and its index increased significantly during pregnancy. A significant increase in A-wave velocity but slight increase in E-wave velocity and a reduction in tissue e' velocity at the septal margin but a progressive increase in a' velocity were also observed (P < 0.05). CONCLUSION: Cardiac chamber dimensions, LV wall thickness, and mass, most indices of LV systolic and diastolic function, though within normal range, were significantly higher in pregnant than in nonpregnant Nigerian women. PMID- 27656093 TI - Current Developments in Interstitial Lung Disease. PMID- 27656096 TI - Discovering Related Clinical Concepts Using Large Amounts of Clinical Notes. AB - The ability to find highly related clinical concepts is essential for many applications such as for hypothesis generation, query expansion for medical literature search, search results filtering, ICD-10 code filtering and many other applications. While manually constructed medical terminologies such as SNOMED CT can surface certain related concepts, these terminologies are inadequate as they depend on expertise of several subject matter experts making the terminology curation process open to geographic and language bias. In addition, these terminologies also provide no quantifiable evidence on how related the concepts are. In this work, we explore an unsupervised graphical approach to mine related concepts by leveraging the volume within large amounts of clinical notes. Our evaluation shows that we are able to use a data driven approach to discovering highly related concepts for various search terms including medications, symptoms and diseases. PMID- 27656095 TI - Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study. AB - Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers. PMID- 27656094 TI - The Role of Laboratory Tests in Crohn's Disease. AB - In the past, laboratory tests were considered of limited value in Crohn's disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies. PMID- 27656098 TI - An extension for the model IMAZ for large absorption. AB - The empirical Ionospheric Model of the Auroral Zone (IMAZ) is based on more than 100,000 electron density profiles measured by the European Incoherent Scatter Radar EISCAT combined with about 100 from sounding rockets. The mathematical procedure applied is a neural network (NN) which works fine as long as one requests predictions from inside the so-called input space, but predicting situations outside it, i.e. for conditions not or only poorly covered by data, are in general utterly unrealistic. An analytical procedure is presented which reasonably extrapolates the NN results for conditions inadequately covered by input data. PMID- 27656097 TI - The Impacts of Educational Asthma Interventions in Schools: A Systematic Review of the Literature. AB - Objective. To review the literature on the impact of educational asthma interventions in schools regarding the knowledge and morbidity of the disease among children and adolescents. Methods. A systematic review was conducted for controlled clinical trials investigating the effectiveness of educational asthma interventions for students, asthmatic or nonasthmatic, families, and school staff. Databases were CENTRAL, PubMed, LILACS, MEDLINE, and SciELO. Articles published in any language were considered, in the period from 2005 to 2014, according to the PRISMA guidelines. Results. Seventeen articles were selected (N = 5,879 subjects). 94% of the interventions (16 of 17 studies) were applied in developed countries that were led by health professionals and most of them targeted asthmatics. Asthma education promotes the improvement of knowledge about the disease in at least one of the evaluated areas. 29% of the interventions (5 of 17 studies) showed a reduction of the asthma symptoms, 35% (6 of 17 studies) reduction of the hospitalization instances and emergency visits, 29% (5 of 17 studies) reduction of school absenteeism, and 41% (7 of 17 studies) increase in the quality of life of the individuals. Conclusions. Educational interventions in schools raise the awareness of asthma and weaken the impact of morbidity indicators. PMID- 27656099 TI - Problems with mapping the auroral oval and magnetospheric substorms. AB - Accurate mapping of the auroral oval into the equatorial plane is critical for the analysis of aurora and substorm dynamics. Comparison of ion pressure values measured at low altitudes by Defense Meteorological Satellite Program (DMSP) satellites during their crossings of the auroral oval, with plasma pressure values obtained at the equatorial plane from Time History of Events and Macroscale Interactions during Substorms (THEMIS) satellite measurements, indicates that the main part of the auroral oval maps into the equatorial plane at distances between 6 and 12 Earth radii. On the nightside, this region is generally considered to be a part of the plasma sheet. However, our studies suggest that this region could form part of the plasma ring surrounding the Earth. We discuss the possibility of using the results found here to explain the ring-like shape of the auroral oval, the location of the injection boundary inside the magnetosphere near the geostationary orbit, presence of quiet auroral arcs in the auroral oval despite the constantly high level of turbulence observed in the plasma sheet, and some features of the onset of substorm expansion. PMID- 27656100 TI - Relationship between wave-like auroral arcs and Pi2 disturbances in plasma sheet prior to substorm onset. AB - Wave-like substorm arc features in the aurora and Pi2 magnetic disturbances observed in the near-Earth plasma sheet are frequently, and sometimes simultaneously, observed around the substorm onset time. We perform statistical analyses of the THEMIS ASI auroral observations that show wave-like bright spot structure along the arc prior to substorm onset. The azimuthal mode number values of the wave-like substorm arcs are found to be in the range of ~100-240 and decrease with increasing geomagnetic latitude of the substorm auroral arc location. We suggest that the azimuthal mode number is likely related to the ion gyroradius and azimuthal wave number. We also perform correlation study of the pre-onset wave-like substorm arc features and Pi2 magnetic disturbances for substorm dipolarization events observed by THEMIS satellites during 2008-2009. The wave-like arc brightness structures on the substorm auroral arcs tend to move azimuthally westward, but with a few exceptions of eastward movement, during tens of seconds prior to the substorm onset. The movement of the wave-like arc brightness structure is linearly correlated with the phase velocity of the Pi2 deltaBy disturbances in the near-Earth plasma sheet region. The result suggests that the Pi2 transverse deltaBy disturbances are related to the intensifying wave like substorm onset arcs. One plausible explanation of the observations is the kinetic ballooning instability, which has high azimuthal mode number due to the ion gyroradius effect and finite parallel electric field that accelerates electrons into the ionosphere to produce the wave-like arc structure. PMID- 27656102 TI - Phase space representation of neutron monitor count rate and atmospheric electric field in relation to solar activity in cycles 21 and 22. AB - Heliospheric modulation of galactic cosmic rays links solar cycle activity with neutron monitor count rate on earth. A less direct relation holds between neutron monitor count rate and atmospheric electric field because different atmospheric processes, including fluctuations in the ionosphere, are involved. Although a full quantitative model is still lacking, this link is supported by solid statistical evidence. Thus, a connection between the solar cycle activity and atmospheric electric field is expected. To gain a deeper insight into these relations, sunspot area (NOAA, USA), neutron monitor count rate (Climax, Colorado, USA), and atmospheric electric field (Lisbon, Portugal) are presented here in a phase space representation. The period considered covers two solar cycles (21, 22) and extends from 1978 to 1990. Two solar maxima were observed in this dataset, one in 1979 and another in 1989, as well as one solar minimum in 1986. Two main observations of the present study were: (1) similar short-term topological features of the phase space representations of the three variables, (2) a long-term phase space radius synchronization between the solar cycle activity, neutron monitor count rate, and potential gradient (confirmed by absolute correlation values above ~0.8). Finally, the methodology proposed here can be used for obtaining the relations between other atmospheric parameters (e.g., solar radiation) and solar cycle activity. PMID- 27656101 TI - Total (fumarolic + diffuse soil) CO2 output from Furnas volcano. AB - Furnas volcano, in Sao Miguel island (Azores), being the surface expression of rising hydrothermal steam, is the site of intense carbon dioxide (CO2) release by diffuse degassing and fumaroles. While the diffusive CO2 output has long (since the early 1990s) been characterized by soil CO2 surveys, no information is presently available on the fumarolic CO2 output. Here, we performed (in August 2014) a study in which soil CO2 degassing survey was combined for the first time with the measurement of the fumarolic CO2 flux. The results were achieved by using a GasFinder 2.0 tunable diode laser. Our measurements were performed in two degassing sites at Furnas volcano (Furnas Lake and Furnas Village), with the aim of quantifying the total (fumarolic + soil diffuse) CO2 output. We show that, within the main degassing (fumarolic) areas, the soil CO2 flux contribution (9.2 t day-1) represents a minor (~15 %) fraction of the total CO2 output (59 t day 1), which is dominated by the fumaroles (~50 t day-1). The same fumaroles contribute to ~0.25 t day-1 of H2S, based on a fumarole CO2/H2S ratio of 150 to 353 (measured with a portable Multi-GAS). However, we also find that the soil CO2 contribution from a more distal wider degassing structure dominates the total Furnas volcano CO2 budget, which we evaluate (summing up the CO2 flux contributions for degassing soils, fumarolic emissions and springs) at ~1030 t day-1. PMID- 27656104 TI - The lasso for high dimensional regression with a possible change point. AB - We consider a high dimensional regression model with a possible change point due to a covariate threshold and develop the lasso estimator of regression coefficients as well as the threshold parameter. Our lasso estimator not only selects covariates but also selects a model between linear and threshold regression models. Under a sparsity assumption, we derive non-asymptotic oracle inequalities for both the prediction risk and the l1-estimation loss for regression coefficients. Since the lasso estimator selects variables simultaneously, we show that oracle inequalities can be established without pretesting the existence of the threshold effect. Furthermore, we establish conditions under which the estimation error of the unknown threshold parameter can be bounded by a factor that is nearly n-1 even when the number of regressors can be much larger than the sample size n. We illustrate the usefulness of our proposed estimation method via Monte Carlo simulations and an application to real data. PMID- 27656103 TI - Standardization of peeling tests for assessing the cohesion and consolidation characteristics of historic stone surfaces. AB - A peeling test known as the "Scotch Tape test" has been used for more than 40 years in conservation practice for assessing the consolidation efficiency of degraded stone. However, the method has not been supported by any standard or reliably verified recommendations for its application. Its applicability is overestimated, and its unrestricted use without adequate knowledge and sufficient understanding can lead to non-comparable, non-reproducible and, in many cases, incorrect and severely biased results and assessments. This paper presents the results of a recent study focused on establishing limits for application, reliable procedures and a "standard" protocol for testing the cohesion characteristics of brittle and quasi-brittle materials, mainly mortars and stones. The main application strategy exploits repeated peeling in the same place on a surface in order to eliminate the effect of the natural decrease in the detached material from the subsurface layers, which might be incorrectly interpreted as a consolidation effect. There is a discussion of factors influencing the performance of the peeling test method, and examples of peeling measurements on various natural and artificial stones are presented. PMID- 27656105 TI - Graphene enterprise: mapping innovation and business development in a strategic emerging technology. AB - This paper explores enterprise development and commercialization in the field of graphene. Firm characteristics and relationships, value chain positioning, and factors associated with product entry are examined for a set of 65 graphene oriented small and medium-sized enterprises located in 16 different countries. As well as secondary sources and bibliometric methods to profile developments in graphene, we use computerized data mining and analytical techniques, including cluster and regression modeling, to identify patterns from publicly available online information on enterprise web sites. We identify groups of graphene small and medium-sized enterprises differentiated by how they are involved with graphene, the materials they target, whether they make equipment, and their orientation toward science and intellectual property. In general, access to finance and the firms' location are significant factors that are associated with graphene product introductions. We also find that patents and scientific publications are not statistically significant predictors of product development in our sample of graphene enterprises. We further identify a cohort of graphene oriented firms that are signaling plans to develop intermediate graphene products that should have higher value in the marketplace. Our findings suggest that policy needs to ensure attention to the introduction and scale-up of downstream intermediate and final graphene products and associated financial, intermediary, and market identification support. The paper demonstrates novel data methods that can be combined with existing information for real-time intelligence to understand and map enterprise development and commercialization in a rapidly emerging and growing new technology. PMID- 27656106 TI - Estimating species diversity and distribution in the era of Big Data: to what extent can we trust public databases? AB - AIM: Massive digitalization of natural history collections is now leading to a steep accumulation of publicly available species distribution data. However, taxonomic errors and geographical uncertainty of species occurrence records are now acknowledged by the scientific community - putting into question to what extent such data can be used to unveil correct patterns of biodiversity and distribution. We explore this question through quantitative and qualitative analyses of uncleaned versus manually verified datasets of species distribution records across different spatial scales. LOCATION: The American tropics. METHODS: As test case we used the plant tribe Cinchoneae (Rubiaceae). We compiled four datasets of species occurrences: one created manually and verified through classical taxonomic work, and the rest derived from GBIF under different cleaning and filling schemes. We used new bioinformatic tools to code species into grids, ecoregions, and biomes following WWF's classification. We analysed species richness and altitudinal ranges of the species. RESULTS: Altitudinal ranges for species and genera were correctly inferred even without manual data cleaning and filling. However, erroneous records affected spatial patterns of species richness. They led to an overestimation of species richness in certain areas outside the centres of diversity in the clade. The location of many of these areas comprised the geographical midpoint of countries and political subdivisions, assigned long after the specimens had been collected. MAIN CONCLUSION: Open databases and integrative bioinformatic tools allow a rapid approximation of large-scale patterns of biodiversity across space and altitudinal ranges. We found that geographic inaccuracy affects diversity patterns more than taxonomic uncertainties, often leading to false positives, i.e. overestimating species richness in relatively species poor regions. Public databases for species distribution are valuable and should be more explored, but under scrutiny and validation by taxonomic experts. We suggest that database managers implement easy ways of community feedback on data quality. PMID- 27656107 TI - Target volume definition for post prostatectomy radiotherapy: Do the consensus guidelines correctly define the inferior border of the CTV? AB - AIM: We compare urethrogram delineation of the caudal aspect of the anastomosis to the recommended guidelines of post prostatectomy radiotherapy. BACKGROUND: Level one evidence has established the indications for, and importance of, adjuvant radiotherapy following radical prostatectomy. Several guidelines have recently addressed delineation of the prostate bed target volume including identification of the vesico-urethral anastomosis, taken as the first CT slice caudal to visible urine in the bladder neck. The inferior border of clinical target volume is then variably defined 5-12 mm below this anastomosis or 15 mm cranial to the penile bulb. METHODS AND MATERIALS: Thirty-three patients who received adjuvant radiotherapy following radical prostatectomy were reviewed. All underwent planning CT with urethrogram. The authors (MM, JC) independently identified the CT slice caudal to the last slice showing urine in the bladder neck (called the CT Reference Slice), and measured the distance between this and the tip of the urethrogram cone. Five patients also had a diagnostic MRI at the time of CT planning to better visualize the anatomy. RESULTS: Sixty-six readings were obtained. The mean distance between the Bladder CT Reference Slice and the most cranial urethrogram contrast slice was 16.1 mm (MM 16.4 mm, JC 15.8 mm), range: 6.8-34.2 mm. The mean distance between the urethrogram tip and the ischial tuberosities was 19.9 mm (range 12.5-29.8 mm). The mean distance between the CT Reference Slice and the ischial tuberosities was 36.9 mm (range 28.3-52.4 mm). CONCLUSIONS: Guidelines for prostate bed radiation post prostatectomy have been developed after publication of the trials proving benefit of such treatment, and are thus untested. The anastomosis is a frequent site of local relapse but is variably defined by the existing guidelines, none of which take into account anatomic patient variation and all of which are at variance with urethrogram data. We recommend the use of planning urethrogram to better delineate the vesico urethral junction and minimize the potential for geographic misses. PMID- 27656109 TI - VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation through macropinocytosis. AB - Endocytosis plays a crucial role in receptor signalling. VEGFR2 (also known as KDR) and its ligand VEGFA are fundamental in neovascularisation. However, our understanding of the role of endocytosis in VEGFR2 signalling remains limited. Despite the existence of diverse internalisation routes, the only known endocytic pathway for VEGFR2 is the clathrin-mediated pathway. Here, we show that this pathway is the predominant internalisation route for VEGFR2 only in the absence of ligand. Intriguingly, VEGFA induces a new internalisation itinerary for VEGFR2, the pathway of macropinocytosis, which becomes the prevalent endocytic route for the receptor in the presence of ligand, whereas the contribution of the clathrin-mediated route becomes minor. Macropinocytic internalisation of VEGFR2, which mechanistically is mediated through the small GTPase CDC42, takes place through macropinosomes generated at ruffling areas of the membrane. Interestingly, macropinocytosis plays a crucial role in VEGFA-induced signalling, endothelial cell functions in vitro and angiogenesis in vivo, whereas clathrin mediated endocytosis is not essential for VEGFA signalling. These findings expand our knowledge on the endocytic pathways of VEGFR2 and suggest that VEGFA-driven internalisation of VEGFR2 through macropinocytosis is essential for endothelial cell signalling and angiogenesis. PMID- 27656108 TI - PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position. AB - Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancer-promoting phosphatase PRL-3 (PTP4A3), which is overexpressed in several epithelial cancers, in polarized epithelial MDCK and Caco2 cells leads to invasion and the formation of multiple ectopic, fully polarized lumens in cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer. The pathological relevance of these findings is supported by the knockdown of endogenous PRL-3 in MCF-7 breast cancer cells grown in three-dimensional branched structures, showing the rescue from multiple-lumen- to single-lumen-containing branch ends. Mechanistically, it has been previously shown that ectopic lumens can arise from midbodies that have been mislocalized through the loss of mitotic spindle orientation or through the loss of asymmetric abscission. Here, we show that PRL 3 triggers ectopic lumen formation through midbody mispositioning without altering the spindle orientation or asymmetric abscission, instead, PRL-3 accelerates cytokinesis, suggesting that this process is an alternative new mechanism for ectopic lumen formation in MDCK cysts. The disruption of epithelial architecture by PRL-3 revealed here is a newly recognized mechanism for PRL-3 promoted cancer progression. PMID- 27656110 TI - Acsl, the Drosophila ortholog of intellectual-disability-related ACSL4, inhibits synaptic growth by altered lipids. AB - Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, including mannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. The MacCer level was elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft associated lipid levels. PMID- 27656111 TI - Rnd3-induced cell rounding requires interaction with Plexin-B2. AB - Rnd proteins are atypical members of the Rho GTPase family that induce actin cytoskeletal reorganization and cell rounding. Rnd proteins have been reported to bind to the intracellular domain of several plexin receptors, but whether plexins contribute to the Rnd-induced rounding response is not known. Here we show that Rnd3 interacts preferentially with plexin-B2 of the three plexin-B proteins, whereas Rnd2 interacts with all three B-type plexins, and Rnd1 shows only very weak interaction with plexin-B proteins in immunoprecipitations. Plexin-B1 has been reported to act as a GAP for R-Ras and/or Rap1 proteins. We show that all three plexin-B proteins interact with R-Ras and Rap1, but Rnd proteins do not alter this interaction or R-Ras or Rap1 activity. We demonstrate that plexin-B2 promotes Rnd3-induced cell rounding and loss of stress fibres, and enhances the inhibition of HeLa cell invasion by Rnd3. We identify the amino acids in Rnd3 that are required for plexin-B2 interaction, and show that mutation of these amino acids prevents Rnd3-induced morphological changes. These results indicate that plexin-B2 is a downstream target for Rnd3, which contributes to its cellular function. PMID- 27656114 TI - Viscosity measurements of crystallizing andesite from Tungurahua volcano (Ecuador). AB - Viscosity has been determined during isothermal crystallization of an andesite from Tungurahua volcano (Ecuador). Viscosity was continuously recorded using the concentric cylinder method and employing a Pt-sheathed alumina spindle at 1 bar and from 1400 degrees C to subliquidus temperatures to track rheological changes during crystallization. The disposable spindle was not extracted from the sample but rather left in the sample during quenching thus preserving an undisturbed textural configuration of the crystals. The inspection of products quenched during the crystallization process reveals evidence for heterogeneous crystal nucleation at the spindle and near the crucible wall, as well as crystal alignment in the flow field. At the end of the crystallization, defined when viscosity is constant, plagioclase is homogeneously distributed throughout the crucible (with the single exception of experiment performed at the lowest temperature). In this experiments, the crystallization kinetics appear to be strongly affected by the stirring conditions of the viscosity determinations. A TTT (Time-Temperature-Transformation) diagram illustrating the crystallization "nose" for this andesite under stirring conditions and at ambient pressure has been constructed. We further note that at a given crystal content and distribution, the high aspect ratio of the acicular plagioclase yields a shear thinning rheology at crystal contents as low as 13 vol %, and that the relative viscosity is higher than predicted from existing viscosity models. These viscosity experiments hold the potential for delivering insights into the relative influences of the cooling path, undercooling, and deformation on crystallization kinetics and resultant crystal morphologies, as well as their impact on magmatic viscosity. PMID- 27656113 TI - Increased ROS production in non-polarized mammary epithelial cells induces monocyte infiltration in 3D culture. AB - Loss of epithelial cell polarity promotes cell invasion and cancer dissemination. Therefore, identification of factors that disrupt polarized acinar formation is crucial. Reactive oxygen species (ROS) drive cancer progression and promote inflammation. Here, we show that the non-polarized breast cancer cell line T4-2 generates significantly higher ROS levels than polarized S1 and T4R cells in three-dimensional (3D) culture, accompanied by induction of the nuclear factor kappaB (NF-kappaB) pathway and cytokine expression. Minimizing ROS in T4-2 cells with antioxidants reestablished basal polarity and inhibited cell proliferation. Introducing constitutively activated RAC1 disrupted cell polarity and increased ROS levels, indicating that RAC1 is a crucial regulator that links cell polarity and ROS generation. We also linked monocyte infiltration with disruption of polarized acinar structure using a 3D co-culture system. Gain- and loss-of function experiments demonstrated that increased ROS in non-polarized cells is necessary and sufficient to enhance monocyte recruitment. ROS also induced cytokine expression and NF-kappaB activity. These results suggest that increased ROS production in mammary epithelial cell leads to disruption of cell polarity and promotes monocyte infiltration. PMID- 27656112 TI - New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis. AB - A number of genes have been linked to familial forms of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Over 150 mutations within the gene encoding superoxide dismutase 1 (SOD1) have been implicated in ALS, but why such mutations lead to ALS-associated cellular dysfunction is unclear. In this study, we identify how ALS-linked SOD1 mutations lead to changes in the cellular health of the yeast Saccharomyces cerevisiae We find that it is not the accumulation of aggregates but the loss of Sod1 protein stability that drives cellular dysfunction. The toxic effect of Sod1 instability does not correlate with a loss of mitochondrial function or increased production of reactive oxygen species, but instead prevents acidification of the vacuole, perturbs metabolic regulation and promotes senescence. Central to the toxic gain-of-function seen with the SOD1 mutants examined was an inability to regulate amino acid biosynthesis. We also report that leucine supplementation results in an improvement in motor function in a Caenorhabditis elegans model of ALS. Our data suggest that metabolic dysfunction plays an important role in Sod1-mediated toxicity in both the yeast and worm models of ALS. PMID- 27656115 TI - Increased rates of large-magnitude explosive eruptions in Japan in the late Neogene and Quaternary. AB - Tephra layers in marine sediment cores from scientific ocean drilling largely record high-magnitude silicic explosive eruptions in the Japan arc for up to the last 20 million years. Analysis of the thickness variation with distance of 180 tephra layers from a global data set suggests that the majority of the visible tephra layers used in this study are the products of caldera-forming eruptions with magnitude (M) > 6, considering their distances at the respective drilling sites to their likely volcanic sources. Frequency of visible tephra layers in cores indicates a marked increase in rates of large magnitude explosive eruptions at ~8 Ma, 6-4 Ma, and further increase after ~2 Ma. These changes are attributed to major changes in tectonic plate interactions. Lower rates of large magnitude explosive volcanism in the Miocene are related to a strike-slip-dominated boundary (and temporary cessation or deceleration of subduction) between the Philippine Sea Plate and southwest Japan, combined with the possibility that much of the arc in northern Japan was submerged beneath sea level partly due to previous tectonic extension of northern Honshu related to formation of the Sea of Japan. Changes in plate motions and subduction dynamics during the ~8 Ma to present period led to (1) increased arc-normal subduction in southwest Japan (and resumption of arc volcanism) and (2) shift from extension to compression of the upper plate in northeast Japan, leading to uplift, crustal thickening and favorable conditions for accumulation of the large volumes of silicic magma needed for explosive caldera-forming eruptions. PMID- 27656116 TI - Organoids as a Model for Colorectal Cancer. AB - Modelling human diseases in in vitro systems is undisputedly an invaluable research tool, yet there are many limitations. Some of those limitations have been overcome through the introduction of organoid culture systems, which have revolutionised colorectal cancer research and enabled an array of new experimental techniques. This 3D system models the physiology, shape, dynamics and cell make-up of the intestinal epithelium producing a relevant and highly adaptable model system. The increased functional relevance of this model compared to the use of 2D cancer cell lines makes it an invaluable tool for both basic and translational research. As the limitations of this system are being overcome to make high-throughput assays possible, it is clear that organoids are becoming a mainstay of colorectal cancer research. This review aims to explore the advantages and limitations of this system and discusses the future directions enabled by this model. PMID- 27656117 TI - Pattern Recognition Approaches for Breast Cancer DCE-MRI Classification: A Systematic Review. AB - We performed a systematic review of several pattern analysis approaches for classifying breast lesions using dynamic, morphological, and textural features in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Several machine learning approaches, namely artificial neural networks (ANN), support vector machines (SVM), linear discriminant analysis (LDA), tree-based classifiers (TC), and Bayesian classifiers (BC), and features used for classification are described. The findings of a systematic review of 26 studies are presented. The sensitivity and specificity are respectively 91 and 83 % for ANN, 85 and 82 % for SVM, 96 and 85 % for LDA, 92 and 87 % for TC, and 82 and 85 % for BC. The sensitivity and specificity are respectively 82 and 74 % for dynamic features, 93 and 60 % for morphological features, 88 and 81 % for textural features, 95 and 86 % for a combination of dynamic and morphological features, and 88 and 84 % for a combination of dynamic, morphological, and other features. LDA and TC have the best performance. A combination of dynamic and morphological features gives the best performance. PMID- 27656118 TI - Distinct Somatic Discrimination Reflected by Laser-Evoked Potentials Using Scalp EEG Leads. AB - Discrimination is an important function in pain processing of the somatic cortex. The involvement of the somatic cortex has been studied using equivalent dipole analysis and neuroimaging, but the results are inconsistent. Scalp electroencephalography (EEG) can reflect functional changes of particular brain regions underneath a lead. However, the responses of EEG leads close to the somatic cortex in response to pain have not been systematically evaluated. The present study applied CO2 laser stimulation to the dorsum of the left hand. Laser evoked potentials (LEPs) of C4, T3, and T4 leads and pain ratings in response to four stimulus intensities were analyzed. LEPs started earlier at the C4 and T4 leads. The onset latency and peak latency of LEPs for C4 and T4 leads were the same. Only 10 of 22 subjects (45 %) presented equivalent current dipoles within the primary somatosensory or motor cortices. LEP amplitudes of these leads increased as stimulation intensity increased. The stimulus-response pattern of the C4 lead was highly correlated with pain rating. In contrast, an S-shaped stimulus-response curve was obtained for the T3 and T4 leads. The present study provides supporting evidence that particular scalp channels are able to reflect the functional characteristics of their underlying cortical areas. Our data strengthen the clinical application of somatic-cortex-related leads for pain discrimination. PMID- 27656119 TI - Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection syndrome." Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD. PMID- 27656120 TI - What Can Neuroscience Tell Us about the Hard Problem of Consciousness? PMID- 27656121 TI - Associations between Family Adversity and Brain Volume in Adolescence: Manual vs. Automated Brain Segmentation Yields Different Results. AB - Associations between brain structure and early adversity have been inconsistent in the literature. These inconsistencies may be partially due to methodological differences. Different methods of brain segmentation may produce different results, obscuring the relationship between early adversity and brain volume. Moreover, adolescence is a time of significant brain growth and certain brain areas have distinct rates of development, which may compromise the accuracy of automated segmentation approaches. In the current study, 23 adolescents participated in two waves of a longitudinal study. Family aggression was measured when the youths were 12 years old, and structural scans were acquired an average of 4 years later. Bilateral amygdalae and hippocampi were segmented using three different methods (manual tracing, FSL, and NeuroQuant). The segmentation estimates were compared, and linear regressions were run to assess the relationship between early family aggression exposure and all three volume segmentation estimates. Manual tracing results showed a positive relationship between family aggression and right amygdala volume, whereas FSL segmentation showed negative relationships between family aggression and both the left and right hippocampi. However, results indicate poor overlap between methods, and different associations were found between early family aggression exposure and brain volume depending on the segmentation method used. PMID- 27656122 TI - Diffusion Capillary Phantom vs. Human Data: Outcomes for Reconstruction Methods Depend on Evaluation Medium. AB - PURPOSE: Diffusion MRI provides a non-invasive way of estimating structural connectivity in the brain. Many studies have used diffusion phantoms as benchmarks to assess the performance of different tractography reconstruction algorithms and assumed that the results can be applied to in vivo studies. Here we examined whether quality metrics derived from a common, publically available, diffusion phantom can reliably predict tractography performance in human white matter tissue. MATERIALS AND METHODS: We compared estimates of fiber length and fiber crossing among a simple tensor model (diffusion tensor imaging), a more complicated model (ball-and-sticks) and model-free (diffusion spectrum imaging, generalized q-sampling imaging) reconstruction methods using a capillary phantom and in vivo human data (N = 14). RESULTS: Our analysis showed that evaluation outcomes differ depending on whether they were obtained from phantom or human data. Specifically, the diffusion phantom favored a more complicated model over a simple tensor model or model-free methods for resolving crossing fibers. On the other hand, the human studies showed the opposite pattern of results, with the model-free methods being more advantageous than model-based methods or simple tensor models. This performance difference was consistent across several metrics, including estimating fiber length and resolving fiber crossings in established white matter pathways. CONCLUSIONS: These findings indicate that the construction of current capillary diffusion phantoms tends to favor complicated reconstruction models over a simple tensor model or model-free methods, whereas the in vivo data tends to produce opposite results. This brings into question the previous phantom based evaluation approaches and suggests that a more realistic phantom or simulation is necessary to accurately predict the relative performance of different tractography reconstruction methods. PMID- 27656124 TI - Lutein and Neurodevelopment in Preterm Infants. PMID- 27656123 TI - Alpha-Synuclein Oligomers-Neurotoxic Molecules in Parkinson's Disease and Other Lewy Body Disorders. AB - Adverse intra- and extracellular effects of toxic alpha-synuclein are believed to be central to the pathogenesis in Parkinson's disease and other disorders with Lewy body pathology in the nervous system. One of the physiological roles of alpha-synuclein relates to the regulation of neurotransmitter release at the presynapse, although it is still unclear whether this mechanism depends on the action of monomers or smaller oligomers. As for the pathogenicity, accumulating evidence suggest that prefibrillar species, rather than the deposits per se, are responsible for the toxicity in affected cells. In particular, larger oligomers or protofibrils of alpha-synuclein have been shown to impair protein degradation as well as the function of several organelles, such as the mitochondria and the endoplasmic reticulum. Accumulating evidence further suggest that oligomers/protofibrils may have a toxic effect on the synapse, which may lead to disrupted electrophysiological properties. In addition, recent data indicate that oligomeric alpha-synuclein species can spread between cells, either as free floating proteins or via extracellular vesicles, and thereby act as seeds to propagate disease between interconnected brain regions. Taken together, several lines of evidence suggest that alpha-synuclein have neurotoxic properties and therefore should be an appropriate molecular target for therapeutic intervention in Parkinson's disease and other disorders with Lewy pathology. In this context, immunotherapy with monoclonal antibodies against alpha-synuclein oligomers/protofibrils should be a particularly attractive treatment option. PMID- 27656125 TI - A vital region for human glycoprotein hormone trafficking revealed by an LHB mutation. AB - Glycoprotein hormones are complex hormonally active macromolecules. Luteinizing hormone (LH) is essential for the postnatal development and maturation of the male gonad. Inactivating Luteinizing hormone beta (LHB) gene mutations are exceptionally rare and lead to hypogonadism that is particularly severe in males. We describe a family with selective LH deficiency and hypogonadism in two brothers. DNA sequencing of LHB was performed and the effects of genetic variants on hormone function and secretion were characterized by mutagenesis studies, confocal microscopy and functional assays. A 20-year-old male from a consanguineous family had pubertal delay, hypogonadism and undetectable LH. A homozygous c.118_120del (p.Lys40del) mutation was identified in the patient and his brother, who subsequently had the same phenotype. Treatment with hCG led to pubertal development, increased circulating testosterone and spermatogenesis. Experiments in HeLa cells revealed that the mutant LH is retained intracellularly and showed diffuse cytoplasmic distribution. The mutated LHB heterodimerizes with the common alpha-subunit and can activate its receptor. Deletion of flanking glutamic acid residues at positions 39 and 41 impair LH to a similar extent as deletion of Lys40. This region is functionally important across all heterodimeric glycoprotein hormones, because deletion of the corresponding residues in hCG, follicle-stimulating hormone and thyroid-stimulating hormone beta-subunits also led to intracellular hormone retention. This novel LHB mutation results in hypogonadism due to intracellular sequestration of the hormone and reveals a discrete region in the protein that is crucial for normal secretion of all human glycoprotein hormones. PMID- 27656127 TI - Decreased Endomorphin-2 and MU-Opioid Receptor in the Spinal Cord Are Associated with Painful Diabetic Neuropathy. AB - Painful diabetic neuropathy (PDN) is one of the most common complications in the early stage of diabetes mellitus (DM). Endomorphin-2 (EM2) selectively activates the MU-opioid receptor (MOR) and subsequently induces antinociceptive effects in the spinal dorsal horn. However, the effects of EM2-MOR in PDN have not yet been clarified in the spinal dorsal horn. Therefore, we aimed to explore the role of EM2-MOR in the pathogenesis of PDN. The main findings were the following: (1) streptozotocin (STZ)-induced diabetic rats exhibited hyperglycemia, body weight loss and mechanical allodynia; (2) in the spinal dorsal horn, the expression levels of EM2 and MOR decreased in diabetic rats; (3) EM2 protein concentrations decreased in the brain, lumbar spinal cord and cerebrospinal fluid (CSF) in diabetic rats but were unchanged in the plasma; (4) the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) was significantly higher in diabetic rats than in control rats; and (5) intrathecal injection of EM2 for 14 days in the early stage of PDN partially alleviated mechanical allodynia and reduced MOR expression in diabetic rats. Our results demonstrate that the EM2-MOR signal may be involved in the early stage of PDN. PMID- 27656126 TI - Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders. AB - The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders. PMID- 27656128 TI - The Drosophila KIF1A Homolog unc-104 Is Important for Site-Specific Synapse Maturation. AB - Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia (HSP), hereditary and sensory autonomic neuropathy type 2 (HSAN2) and non-syndromic intellectual disability (ID). Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study, we use a previously described hypomorphic allele of unc-104, unc-104(bris) , to investigate the impact of partial loss-of-function of kinesin-3 on synapse maturation at the Drosophila neuromuscular junction (NMJ). Unc-104(bris) mutants exhibit structural defects where a subset of synapses at the NMJ lack all investigated active zone (AZ) proteins, suggesting a complete failure in the formation of the cytomatrix at the active zone (CAZ) at these sites. Modulating synaptic Bruchpilot (Brp) levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of AZ components such as Ca(2+) channels and Liprin-alpha is caused by impaired kinesin 3 based transport rather than due to the absence of the key AZ organizer protein, Brp. In addition to defects in CAZ assembly, unc-104(bris) mutants display further defects such as depletion of dense core and synaptic vesicle (SV) markers from the NMJ. Notably, the level of Rab3, which is important for the allocation of AZ proteins to individual release sites, was severely reduced at unc-104(bris) mutant NMJs. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104(bris) larvae, suggesting that lack of presynaptic Rab3 contributes to defects in synapse maturation. PMID- 27656129 TI - Axon Branch-Specific Semaphorin-1a Signaling in Drosophila Mushroom Body Development. AB - Correct wiring of the mushroom body (MB) neuropil in the Drosophila brain involves appropriate positioning of different axonal lobes, as well as the sister branches that develop from individual axons. This positioning requires the integration of various guidance cues provided by different cell types, which help the axons find their final positions within the neuropil. Semaphorins are well known for their conserved roles in neuronal development and axon guidance. We investigated the role of Sema-1a in MB development more closely. We show that Sema-1a is expressed in the MBs as well as surrounding structures, including the glial transient interhemispheric fibrous ring, throughout development. By loss- and gain-of-function experiments, we show that the MB axons display lobe and sister branch-specific Sema-1a signaling, which controls different aspects of axon outgrowth and guidance. Furthermore, we demonstrate that these effects are modulated by the integration of MB intrinsic and extrinsic Sema-1a signaling pathways involving PlexA and PlexB. Finally, we also show a role for neuronal- glial interaction in Sema-1a dependent beta-lobe outgrowth. PMID- 27656130 TI - A Sex Pheromone Receptor in the Hessian Fly Mayetiola destructor (Diptera, Cecidomyiidae). AB - The Hessian fly, Mayetiola destructor Say (Diptera, Cecidomyiidae), is a pest of wheat and belongs to a group of gall-inducing herbivores. This species has a unique life history and several ecological features that differentiate it from other Diptera such as Drosophila melanogaster and blood-feeding mosquitoes. These features include a short, non-feeding adult life stage (1-2 days) and the use of a long-range sex pheromone produced and released by adult females. Sex pheromones are detected by members of the odorant receptor (OR) family within the Lepidoptera, but no receptors for similar long-range sex pheromones have been characterized from the Diptera. Previously, 122 OR genes have been annotated from the Hessian fly genome, with many of them showing sex-biased expression in the antennae. Here we have expressed, in HEK293 cells, five MdesORs that display male biased expression in antennae, and we have identified MdesOR115 as a Hessian fly sex pheromone receptor. MdesOR115 responds primarily to the sex pheromone component (2S,8E,10E)-8,10-tridecadien-2-yl acetate, and secondarily to the corresponding Z,E-isomer. Certain sensory neuron membrane proteins (i.e., SNMP1) are important for responses of pheromone receptors in flies and moths. The Hessian fly genome is unusual in that it encodes six SNMP1 paralogs, of which five are expressed in antennae. We co-expressed each of the five antennal SNMP1 paralogs together with each of the five candidate sex pheromone receptors from the Hessian fly and found that they do not influence the response of MdesOR115, nor do they confer responsiveness in any of the non-responsive ORs to any of the sex pheromone components identified to date in the Hessian fly. Using Western blots, we detected protein expression of MdesOrco, all MdesSNMPs, and all MdesORs except for MdesOR113, potentially explaining the lack of response from this OR. In conclusion, we report the first functional characterization of an OR from the Cecidomyiidae, extending the role of ORs as long-range sex pheromone detectors from the Lepidoptera into the Diptera. PMID- 27656133 TI - Importance of Proprioceptive Information for Postural Control in Children with Strabismus before and after Strabismus Surgery. AB - The objective of this study is to examine the role of proprioception in postural balance in children with strabismus before and after realignment of their visual axes by eye surgery. Postural recordings were made with the TechnoConcept(r) force platform in 23 children. Several conditions were studied, whether the subjects had both eyes open, or either the dominant or the non-dominant eye open, without and with foam pads of 4 mm underfoot. Recordings were performed before and after strabismus surgery. The surface area, the length and the mean speed of the center of pressure (CoP) were analyzed. Before strabismus surgery, all children showed better stability with both eyes open with respect to the condition with the non-dominant eye open; furthermore postural stability improved in the presence of foam pads. After surgery, the surface area of CoP decreased significantly, especially in the non-dominant eye viewing condition. We suggest that strabismic children use mainly proprioceptive information in order to control their posture, but also visual inputs, which are important for obtaining a good postural stability. The alignment of the visual axes after surgery provides enhanced postural stability, suggesting, again the major role of visual inputs in the control of posture. Proprioceptive plasticity after strabismus surgery may allow better visual rehabilitation. PMID- 27656131 TI - The Wiring of Developing Sensory Circuits-From Patterned Spontaneous Activity to Synaptic Plasticity Mechanisms. AB - In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarizations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now support the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005b; Rochefort et al., 2011; Zhang et al., 2012; Ko et al., 2013). In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (opto)genetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we intend to outline the most recent descriptions of spontaneous activity patterns in rodent developing sensory areas, as well as the inferences we can make about the information content of those activity patterns and ideas about the plasticity rules that allow this activity to shape the young brain. PMID- 27656132 TI - Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study. AB - The cingulum bundle (CB) is a critical white matter fiber tract in the brain, which forms connections between the frontal lobe, parietal lobe and temporal lobe. In non-human primates, the CB is actually divided into distinct subcomponents on the basis of corticocortical connections. However, at present, no study has verified similar distinct subdivisions in the human brain. In this study, we reconstructed these distinct subdivisions in the human brain, and determined their exact cortical connections using high definition fiber tracking (HDFT) technique on 10 healthy adults and a 488-subject template from the Human Connectome Project (HCP-488). Fiber dissections were performed to verify tractography results. Five CB segments were identified. CB-I ran from the subrostral areas to the precuneus and splenium, encircling the corpus callosum (CC). CB-II arched around the splenium and extended anteriorly above the CC to the medial aspect of the superior frontal gyrus (SFG). CB-III connected the superior parietal lobule (SPL) and precuneus with the medial aspect of the SFG. CB-IV was a relatively minor subcomponent from the SPL and precuneus to the frontal region. CB-V, the para-hippocampal cingulum, stemmed from the medial temporal lobe and fanned out to the occipital lobes. Our findings not only provide a more accurate and detailed description on the associated architecture of the subcomponents within the CB, but also offer new insights into the functional role of the CB in the human brain. PMID- 27656134 TI - Non-Type b Haemophilus influenzae Invasive Infections in North Dakota and South Dakota, 2013-2015. AB - Reports of children with non-type b Haemophilus influenzae infection in the United States in recent years have been limited. Here, we report the spectrum and severity of disease associated with invasive non-type b H influenzae infection in 17 patients at 2 tertiary-care children's hospitals over a 2-year period. Meningitis was the most common diagnosis. The majority of the patients had neurologic sequelae, and 1 patient died. The high proportions of hospitalization, intensive care utilization, and neurologic complications reveal that non-type b H influenzae infection was associated with significant morbidity in this pediatric population. PMID- 27656135 TI - Dorsal Raphe Nucleus Down-Regulates Medial Prefrontal Cortex during Experience of Flow. AB - Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A "flow" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of "boredom" and "overload". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of flow. The AMY was down-regulated irrespective of condition. The present results suggest a causal role for the DRN in modulating the MPFC, contributing to the experience of flow. PMID- 27656136 TI - Concurrence of High Fat Diet and APOE Gene Induces Allele Specific Metabolic and Mental Stress Changes in a Mouse Model of Alzheimer's Disease. AB - Aging is the main risk factor for neurodegenerative diseases, including Alzheimer's disease (AD). However, evidence indicates that the pathological process begins long before actual cognitive or pathological symptoms are apparent. The long asymptomatic phase and complex integration between genetic, environmental and metabolic factors make it one of the most challenging diseases to understand and cure. In the present study, we asked whether an environmental factor such as high-fat (HF) diet would synergize with a genetic factor to affect the metabolic and cognitive state in the Apolipoprotein E (ApoE4) mouse model of AD. Our data suggest that a HF diet induces diabetes mellitus (DM)-like metabolism in ApoE4 mice, as well as changes in beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protein levels between the two ApoE strains. Furthermore, HF diet induces anxiety in this AD mouse model. Our results suggest that young ApoE4 carriers are prone to psychological stress and metabolic abnormalities related to AD, which can easily be triggered via HF nutrition. PMID- 27656137 TI - Altered Effective Connectivity among Core Neurocognitive Networks in Idiopathic Generalized Epilepsy: An fMRI Evidence. AB - Idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizures (GTCS) suffer long-term cognitive impairments, and present a higher incidence of psychosocial and psychiatric disturbances than healthy people. It is possible that the cognitive dysfunctions and higher psychopathological risk in IGE-GTCS derive from disturbed causal relationship among core neurocognitive brain networks. To test this hypothesis, we examined the effective connectivity across the salience network (SN), default mode network (DMN), and central executive network (CEN) using resting-state functional magnetic resonance imaging (fMRI) data collected from 27 IGE-GTCS patients and 29 healthy controls. In the study, a combination framework of time domain and frequency domain multivariate Granger causality analysis was firstly proposed, and proved to be valid and accurate by simulation experiments. Using this method, we then observed significant differences in the effective connectivity graphs between the patient and control groups. Specifically, between-group statistical analysis revealed that relative to the healthy controls, the patients established significantly enhanced Granger causal influence from the dorsolateral prefrontal cortex to the dorsal anterior cingulate cortex, which is coherent both in the time and frequency domains analyses. Meanwhile, time domain analysis also revealed decreased Granger causal influence from the right fronto-insular cortex to the posterior cingulate cortex in the patients. These findings may provide new evidence for functional brain organization disruption underlying cognitive dysfunctions and psychopathological risk in IGE-GTCS. PMID- 27656138 TI - Anticipatory Postural Control of Stability during Gait Initiation Over Obstacles of Different Height and Distance Made Under Reaction-Time and Self-Initiated Instructions. AB - Despite the abundant literature on obstacle crossing in humans, the question of how the central nervous system (CNS) controls postural stability during gait initiation with the goal to clear an obstacle remains unclear. Stabilizing features of gait initiation include anticipatory postural adjustments (APAs) and lateral swing foot placement. To answer the above question, 14 participants initiated gait as fast as possible in three conditions of obstacle height, three conditions of obstacle distance and one obstacle-free (control) condition. Each of these conditions was performed with two levels of temporal pressure: reaction time (high-pressure) and self-initiated (low-pressure) movements. A mechanical model of the body falling laterally under the influence of gravity and submitted to an elastic restoring force is proposed to assess the effect of initial (foot off) center-of-mass position and velocity (or "initial center-of-mass set") on the stability at foot-contact. Results showed that the anticipatory peak of mediolateral (ML) center-of-pressure shift, the initial ML center-of-mass velocity and the duration of the swing phase, of gait initiation increased with obstacle height, but not with obstacle distance. These results suggest that ML APAs are scaled with swing duration in order to maintain an equivalent stability across experimental conditions. This statement is strengthened by the results obtained with the mechanical model, which showed how stability would be degraded if there was no adaptation of the initial center-of-mass set to swing duration. The anteroposterior (AP) component of APAs varied also according to obstacle height and distance, but in an opposite way to the ML component. Indeed, results showed that the anticipatory peak of backward center-of-pressure shift and the initial forward center-of-mass set decreased with obstacle height, probably in order to limit the risk to trip over the obstacle, while the forward center-of mass velocity at foot-off increased with obstacle distance, allowing a further step to be taken. These effects of obstacle height and distance were globally similar under low and high-temporal pressure. Collectively, these findings imply that the CNS is able to predict the potential instability elicited by the obstacle clearance and that it scales the spatiotemporal parameters of APAs accordingly. PMID- 27656139 TI - Deconstructing the Emotion Regulatory Properties of Mindfulness: An Electrophysiological Investigation. AB - The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects-differentiated as a meditative practice, state of mind and dispositional trait-on the late positive potential (LPP), an event-related potentials (ERPs) indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully) failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice. PMID- 27656140 TI - Deep Learning with Convolutional Neural Networks Applied to Electromyography Data: A Resource for the Classification of Movements for Prosthetic Hands. AB - Natural control methods based on surface electromyography (sEMG) and pattern recognition are promising for hand prosthetics. However, the control robustness offered by scientific research is still not sufficient for many real life applications, and commercial prostheses are capable of offering natural control for only a few movements. In recent years deep learning revolutionized several fields of machine learning, including computer vision and speech recognition. Our objective is to test its methods for natural control of robotic hands via sEMG using a large number of intact subjects and amputees. We tested convolutional networks for the classification of an average of 50 hand movements in 67 intact subjects and 11 transradial amputees. The simple architecture of the neural network allowed to make several tests in order to evaluate the effect of pre processing, layer architecture, data augmentation and optimization. The classification results are compared with a set of classical classification methods applied on the same datasets. The classification accuracy obtained with convolutional neural networks using the proposed architecture is higher than the average results obtained with the classical classification methods, but lower than the results obtained with the best reference methods in our tests. The results show that convolutional neural networks with a very simple architecture can produce accurate results comparable to the average classical classification methods. They show that several factors (including pre-processing, the architecture of the net and the optimization parameters) can be fundamental for the analysis of sEMG data. Larger networks can achieve higher accuracy on computer vision and object recognition tasks. This fact suggests that it may be interesting to evaluate if larger networks can increase sEMG classification accuracy too. PMID- 27656141 TI - Regional Gray Matter Atrophy Coexistent with Occipital Periventricular White Matter Hyper Intensities. AB - White matter hyperintensities (WMHs) and brain atrophy often coexist in the elderly. Additionally, WMH is often observed as occipital periventricular hyperintensities (OPVHs) with low-grade periventricular (PV) white matter (WM) lesions and is usually confined within an anatomical structure. However, the effects of OPVHs on gray matter (GM) atrophy remain largely unknown. In this study, we investigated GM atrophy in OPVHs patients and explored the relationship between such atrophy and clinical risk factors. T1-weighted and T2-weighted Magnetic resonance imaging (MRI) were acquired, and voxel-based morphometry (VBM) analysis was applied. The clinical (demographic and cardiovascular) risk factors of the OPVHs patients and healthy controls were then compared. Lastly, scatter plots and correlation analysis were applied to explore the relationship between the MRI results and clinical risk factors in the OPVHs patients. OPVHs patients had significantly reduced GM in the right supramarginal gyrus, right angular gyrus, right middle temporal gyrus, right anterior cingulum and left insula compared to healthy controls. Additionally, OPVHs patients had GM atrophy in the left precentral gyrus and left insula cortex, and such atrophy is associated with a reduction in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B). PMID- 27656142 TI - Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study. AB - The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5 lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both). PMID- 27656144 TI - Hypoglycemic Activity and the Potential Mechanism of the Flavonoid Rich Extract from Sophora tonkinensis Gagnep. in KK-Ay Mice. AB - This study investigated the active principles, hypoglycemic activity and potential mechanisms of the flavonoid rich extract from Sophora tonkinensis Gagnep. (ST-EtOAc) in KK-Ay diabetic mice. An off-line semipreparative liquid chromatography-nuclear magnetic resonance (LC-NMR) and liquid chromatography ultraviolet-electrospray ionization mass spectrometry (LC-UV-ESIMS) protocol was performed to determine 13 flavonoids from ST-EtOAc. ST-EtOAc administrated orally to the KK-Ay mice significantly increased their sensibility to insulin, reduced fasting blood-glucose levels and blood lipid indexes such as triglyceride and cholesterol. Moreover, ST-EtOAc exhibited a strong effect of stimulation on glucose transporter 4 (GLUT4) translocation by 2.7-fold in L6 cells. However, the selective AMP-activated protein kinase (AMPK) inhibitor compound C can completely inhibit the activation of the AMPK pathway and prevent the GLUT4 translocation caused by ST-EtOAc. In vivo, phosphorylation of the AMPK expression in the liver and skeletal muscle was measured. The results showed phosphorylation of the AMPK had been improved and GLUT4 expression had been also enhanced. In this paper, we conclude that, ST-EtOAc seems to have potential beneficial effects on the treatment of type 2 diabetes mellitus with the probable mechanism of stimulating GLUT4 translocation modulated by the AMPK pathway. PMID- 27656145 TI - Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress. AB - The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF alpha, Il-1beta, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation. PMID- 27656146 TI - Protective Effect of Cyanidin-3-O-Glucoside against Ultraviolet B Radiation Induced Cell Damage in Human HaCaT Keratinocytes. AB - Ultraviolet radiation is the major environmental harmful factor that has emotional impact on human skin. The aim of the present study was to determine the mechanism of protection of cyanidin-3-O-glucoside against ultraviolet B (UVB) induced damage to human HaCaT keratinocytes. Our results show that cyanidin-3-O glucoside decreased the levels of intracellular reactive oxygen species generated by UVB treatment. Cyanidin-3-O-glucoside also decreased the UVB-augmented levels of the DNA damage indicators phospho-p53 and phospho-ATM/ATR. In addition, cyanidin-3-O-glucoside protected keratinocytes from UVB-induced injury by overturning the disruption of mitochondrial membrane potential and reversing apoptosis. The expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) was attenuated in UVB-exposed cells but restored in UVB/cyanidin-3-O-glucoside treated cells. Furthermore, expression of the proapoptotic proteins Bcl-2 associated X (Bax) and the key apoptosis executer cleaved caspase-3 were increased in UVB-irradiated cells and decreased in UVB/cyanidin-3-O-glucoside treated cells. For these reasons, the results demonstrate that cyanidin-3-O glucoside protects human keratinocytes against UVB-induced oxidative stress and apoptosis. Our study provides a theoretical basis for the use of cyanidin-3-O glucoside in the fight against light damage. PMID- 27656147 TI - Molecular Properties of Globin Channels and Pores: Role of Cholesterol in Ligand Binding and Movement. AB - Globins contain one or more cavities that control or affect such functions as ligand movement and ligand binding. Here we report that the extended globin family [cytoglobin (Cygb); neuroglobin (Ngb); myoglobin (Mb); hemoglobin (Hb) subunits Hba(alpha); and Hbb(beta)] contain either a transmembrane (TM) helix or pore-lining region as well as internal cavities. Protein motif/domain analyses indicate that Ngb and Hbb each contain 5 cholesterol- binding (CRAC/CARC) domains and 1 caveolin binding motif, whereas the Cygb dimer has 6 cholesterol-binding domains but lacks caveolin-binding motifs. Mb and Hba each exhibit 2 cholesterol binding domains and also lack caveolin-binding motifs. The Hb alphabeta-tetramer contains 14 cholesterol-binding domains. Computer algorithms indicate that Cygb and Ngb cavities display multiple partitions and C-terminal pore-lining regions, whereas Mb has three major cavities plus a C-terminal pore-lining region. The Hb tetramer exhibits a large internal cavity but the subunits differ in that they contain a C-terminal TM helix (Hba) and pore-lining region (Hbb). The cavities include 43 of 190 Cygb residues, 38 of 151 of Ngb residues, 55 of 154 Mb residues, and 137 of 688 residues in the Hb tetramer. Each cavity complex includes 6 to 8 residues of the TM helix or pore-lining region and CRAC/CARC domains exist within all cavities. Erythrocyte Hb alphabeta-tetramers are largely cytosolic but also bind to a membrane anion exchange protein, "band 3," which contains a large internal cavity and 12 TM helices (5 being pore-lining regions). The Hba TM helix may be the erythrocyte membrane "band 3" attachment site. "Band 3" contributes 4 caveolin binding motifs and 10 CRAC/CARC domains. Cholesterol binding may create lipid-disordered phases that alter globin cavities and facilitate ligand movement, permitting ion channel formation and conformational changes that orchestrate anion and ligand (O2, CO2, NO) movement within the large internal cavities and channels of the globins. PMID- 27656143 TI - CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis. AB - Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients' debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID- 27656151 TI - Sleep Paralysis in Brazilian Folklore and Other Cultures: A Brief Review. AB - Sleep paralysis (SP) is a dissociative state that occurs mainly during awakening. SP is characterized by altered motor, perceptual, emotional and cognitive functions, such as inability to perform voluntary movements, visual hallucinations, feelings of chest pressure, delusions about a frightening presence and, in some cases, fear of impending death. Most people experience SP rarely, but typically when sleeping in supine position; however, SP is considered a disease (parasomnia) when recurrent and/or associated to emotional burden. Interestingly, throughout human history, different peoples interpreted SP under a supernatural view. For example, Canadian Eskimos attribute SP to spells of shamans, who hinder the ability to move, and provoke hallucinations of a shapeless presence. In the Japanese tradition, SP is due to a vengeful spirit who suffocates his enemies while sleeping. In Nigerian culture, a female demon attacks during dreaming and provokes paralysis. A modern manifestation of SP is the report of "alien abductions", experienced as inability to move during awakening associated with visual hallucinations of aliens. In all, SP is a significant example of how a specific biological phenomenon can be interpreted and shaped by different cultural contexts. In order to further explore the ethnopsychology of SP, in this review we present the "Pisadeira", a character of Brazilian folklore originated in the country's Southeast, but also found in other regions with variant names. Pisadeira is described as a crone with long fingernails who lurks on roofs at night and tramples on the chest of those who sleep on a full stomach with the belly up. This legend is mentioned in many anthropological accounts; however, we found no comprehensive reference on the Pisadeira from the perspective of sleep science. Here, we aim to fill this gap. We first review the neuropsychological aspects of SP, and then present the folk tale of the Pisadeira. Finally, we summarize the many historical and artistic manifestations of SP in different cultures, emphasizing the similarities and differences with the Pisadeira. PMID- 27656150 TI - Mesenchymal Remodeling during Palatal Shelf Elevation Revealed by Extracellular Matrix and F-Actin Expression Patterns. AB - During formation of the secondary palate in mammalian embryos, two vertically oriented palatal shelves rapidly elevate into a horizontal position above the tongue, meet at the midline, and fuse to form a single entity. Previous observations suggested that elevation occurs by a simple 90 degrees rotation of the palatal shelves. More recent findings showed that the presumptive midline epithelial cells are not located at the tips of palatal shelves before elevation, but mostly toward their medial/lingual part. This implied extensive tissue remodeling during shelf elevation. Nevertheless, it is still not known how the shelf mesenchyme reorganizes during this process, and what mechanism drives it. To address this question, we mapped the distinct and restricted expression domains of certain extracellular matrix components within the developing palatal shelves. This procedure allowed to monitor movements of entire mesenchymal regions relative to each other during shelf elevation. Consistent with previous notions, our results confirm a flipping movement of the palatal shelves anteriorly, whereas extensive mesenchymal reorganization is observed more posteriorly. There, the entire lingual portion of the vertical shelves moves close to the midline after elevation, whereas the mesenchyme at the original tip of the shelves ends up ventrolaterally. Moreover, we observed that the mesenchymal cells of elevating palatal shelves substantially align their actin cytoskeleton, their extracellular matrix, and their nuclei in a ventral to medial direction. This indicates that, like in other morphogenetic processes, actin dependent cell contractility is a major driving force for mesenchymal tissue remodeling during palatogenesis. PMID- 27656149 TI - Purification and Partial Characterization of Trypsin-Specific Proteinase Inhibitors from Pigeonpea Wild Relative Cajanus platycarpus L. (Fabaceae) Active against Gut Proteases of Lepidopteran Pest Helicoverpa armigera. AB - Proteinase inhibitors (PIs) are natural defense proteins of plants found to be active against gut proteases of various insects. A pigeonpea wild relative Cajanus platycarpus was identified as a source of resistance against Helicoverpa armigera, a most devastating pest of several crops including pigeonpea. In the light of earlier studies, trypsin-specific PIs (CpPI 63) were purified from mature dry seeds of C. platycarpus (ICPW-63) and characterized their biochemical properties in contributing to H. armigera resistance. CpPI 63 possessed significant H. armigera gut trypsin-like proteinase inhibitor (HGPI) activity than trypsin inhibitor (TI) activity. Analysis of CpPI 63 using two-dimensional (2-D) electrophoresis and matrix assisted laser desorption ionization time-of flight (MALDI-TOF) mass spectrometry revealed that it contained several isoinhibitors and small oligomers with masses ranging between 6 and 58 kDa. The gelatin activity staining studies suggest that these isoinhibitors and oligomers possessed strong inhibitory activity against H. armigera gut trypsin-like proteases (HGPs). The N-terminal sequence of the isoinhibitors (pI 6.6 and pI 5.6) of CpPI 63 exhibited 80% homology with several Kunitz trypsin inhibitors (KTIs) as well as miraculin-like proteins (MLPs). Further, modification of lysine residue(s) lead to 80% loss in both TI and HGPI activities of CpPI 63. In contrast, the TI and HGPI activities of CpPI 63 were stable over a wide range of temperature and pH conditions. The reported results provide a biochemical basis for pod borer resistance in C. platycarpus. PMID- 27656152 TI - How Traumatic Violence Permanently Changes Shopping Behavior. AB - Traumatic experiences - such as combat, living in a conflict country or war-torn nation, or experiencing a violent crime or natural disaster - change social relationships and may also influence a life-time of consumer relationships with brands and shopping. Our focus on this previously overlooked area is centered on an analysis of the long-term shopping habits of 355 combat veterans. We show that those who experienced heavy trauma (e.g., heavy combat) exhibited similar disconnection from brands as others have experienced in social relationships. They became more transactional in that they were more open to switching brands, to trying new products, and buying the least expensive alternative (p < 0.01). In contrast, those who had experienced a light trauma were more influenced by ads and more open to buying brands even when they cost more (p < 0.00). Trauma, such as combat, may change one's decision horizon. Functionality and price become more important, which is consistent with the idea that they are more focused on the present moment than on building on the past or saving for the future. PMID- 27656148 TI - Obesity, Inflammation, and Exercise Training: Relative Contribution of iNOS and eNOS in the Modulation of Vascular Function in the Mouse Aorta. AB - BACKGROUND: The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process. METHODS: High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFalpha was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown. RESULTS: Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS(-/-) animals. The decreased contractility was endothelium dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFalpha, TNF receptor 1, and phospho-IkappaB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet-fed animals, decreased iNOS expression, and increased eNOS expression. CONCLUSION: Obesity caused endothelium dysfunction, TNFalpha, and iNOS pathway up-regulation, decreasing vascular contractility in the obese animals. Exercise training was an effective therapy to control iNOS-dependent NO production and to preserve endothelial function in obese individuals. PMID- 27656154 TI - Processing of Individual Items during Ensemble Coding of Facial Expressions. AB - There is growing evidence that human observers are able to extract the mean emotion or other type of information from a set of faces. The most intriguing aspect of this phenomenon is that observers often fail to identify or form a representation for individual faces in a face set. However, most of these results were based on judgments under limited processing resource. We examined a wider range of exposure time and observed how the relationship between the extraction of a mean and representation of individual facial expressions would change. The results showed that with an exposure time of 50 ms for the faces, observers were more sensitive to mean representation over individual representation, replicating the typical findings in the literature. With longer exposure time, however, observers were able to extract both individual and mean representation more accurately. Furthermore, diffusion model analysis revealed that the mean representation is also more prone to suffer from the noise accumulated in redundant processing time and leads to a more conservative decision bias, whereas individual representations seem more resistant to this noise. Results suggest that the encoding of emotional information from multiple faces may take two forms: single face processing and crowd face processing. PMID- 27656153 TI - Comparing Auditory Noise Treatment with Stimulant Medication on Cognitive Task Performance in Children with Attention Deficit Hyperactivity Disorder: Results from a Pilot Study. AB - BACKGROUND: Recent research has shown that acoustic white noise (80 dB) can improve task performance in people with attention deficits and/or Attention Deficit Hyperactivity Disorder (ADHD). This is attributed to the phenomenon of stochastic resonance in which a certain amount of noise can improve performance in a brain that is not working at its optimum. We compare here the effect of noise exposure with the effect of stimulant medication on cognitive task performance in ADHD. The aim of the present study was to compare the effects of auditory noise exposure with stimulant medication for ADHD children on a cognitive test battery. A group of typically developed children (TDC) took the same tests as a comparison. METHODS: Twenty children with ADHD of combined or inattentive subtypes and twenty TDC matched for age and gender performed three different tests (word recall, spanboard and n-back task) during exposure to white noise (80 dB) and in a silent condition. The ADHD children were tested with and without central stimulant medication. RESULTS: In the spanboard- and the word recall tasks, but not in the 2-back task, white noise exposure led to significant improvements for both non-medicated and medicated ADHD children. No significant effects of medication were found on any of the three tasks. CONCLUSION: This pilot study shows that exposure to white noise resulted in a task improvement that was larger than the one with stimulant medication thus opening up the possibility of using auditory noise as an alternative, non-pharmacological treatment of cognitive ADHD symptoms. PMID- 27656155 TI - Sociocultural Influences on Moral Judgments: East-West, Male-Female, and Young Old. AB - Gender, age, and culturally specific beliefs are often considered relevant to observed variation in social interactions. At present, however, the scientific literature is mixed with respect to the significance of these factors in guiding moral judgments. In this study, we explore the role of each of these factors in moral judgment by presenting the results of a web-based study of Eastern (i.e., Russia) and Western (i.e., USA, UK, Canada) subjects, male and female, and young and old. Participants (n = 659) responded to hypothetical moral scenarios describing situations where sacrificing one life resulted in saving five others. Though men and women from both types of cultures judged (1) harms caused by action as less permissible than harms caused by omission, (2) means-based harms as less permissible than side-effects, and (3) harms caused by contact as less permissible than by non-contact, men in both cultures delivered more utilitarian judgments (save the five, sacrifice one) than women. Moreover, men from Western cultures were more utilitarian than Russian men, with no differences observed for women. In both cultures, older participants delivered less utilitarian judgments than younger participants. These results suggest that certain core principles may mediate moral judgments across different societies, implying some degree of universality, while also allowing a limited range of variation due to sociocultural factors. PMID- 27656157 TI - Personality and Social Framing in Privacy Decision-Making: A Study on Cookie Acceptance. AB - Despite their best intentions, people struggle with the realities of privacy protection and will often sacrifice privacy for convenience in their online activities. Individuals show systematic, personality dependent differences in their privacy decision making, which makes it interesting for those who seek to design 'nudges' designed to manipulate privacy behaviors. We explore such effects in a cookie decision task. Two hundred and ninety participants were given an incidental website review task that masked the true aim of the study. At the task outset, they were asked whether they wanted to accept a cookie in a message that either contained a social framing 'nudge' (they were told that either a majority or a minority of users like themselves had accepted the cookie) or contained no information about social norms (control). At the end of the task, participants were asked to complete a range of personality assessments (impulsivity, risk taking, willingness to self-disclose and sociability). We found social framing to be an effective behavioral nudge, reducing cookie acceptance in the minority social norm condition. Further, we found personality effects in that those scoring highly on risk-taking and impulsivity were significantly more likely to accept the cookie. Finally, we found that the application of a social nudge could attenuate the personality effects of impulsivity and risk-taking. We explore the implications for those working in the privacy-by-design space. PMID- 27656156 TI - Factor Structure, Reliability and Measurement Invariance of the Alberta Context Tool and the Conceptual Research Utilization Scale, for German Residential Long Term Care. AB - We translated the Canadian residential long term care versions of the Alberta Context Tool (ACT) and the Conceptual Research Utilization (CRU) Scale into German, to study the association between organizational context factors and research utilization in German nursing homes. The rigorous translation process was based on best practice guidelines for tool translation, and we previously published methods and results of this process in two papers. Both instruments are self-report questionnaires used with care providers working in nursing homes. The aim of this study was to assess the factor structure, reliability, and measurement invariance (MI) between care provider groups responding to these instruments. In a stratified random sample of 38 nursing homes in one German region (Metropolregion Rhein-Neckar), we collected questionnaires from 273 care aides, 196 regulated nurses, 152 allied health providers, 6 quality improvement specialists, 129 clinical leaders, and 65 nursing students. The factor structure was assessed using confirmatory factor models. The first model included all 10 ACT concepts. We also decided a priori to run two separate models for the scale based and the count-based ACT concepts as suggested by the instrument developers. The fourth model included the five CRU Scale items. Reliability scores were calculated based on the parameters of the best-fitting factor models. Multiple group confirmatory factor models were used to assess MI between provider groups. Rather than the hypothesized ten-factor structure of the ACT, confirmatory factor models suggested 13 factors. The one-factor solution of the CRU Scale was confirmed. The reliability was acceptable (>0.7 in the entire sample and in all provider groups) for 10 of 13 ACT concepts, and high (0.90-0.96) for the CRU Scale. We could demonstrate partial strong MI for both ACT models and partial strict MI for the CRU Scale. Our results suggest that the scores of the German ACT and the CRU Scale for nursing homes are acceptably reliable and valid. However, as the ACT lacked strict MI, observed variables (or scale scores based on them) cannot be compared between provider groups. Rather, group comparisons should be based on latent variable models, which consider the different residual variances of each group. PMID- 27656159 TI - Cotard Delusion in the Context of Schizophrenia: A Case Report and Review of the Literature. AB - BACKGROUND: The Cotard delusion (CD) is one of a variety of narrowly defined monothematic delusions characterized by nihilistic beliefs about the body's existence or life itself. The presence of CD within the context of schizophrenia is rare (<1%), and remains understudied. CASE: 'Mr. C' is a 58-year-old veteran with a prior diagnosis of schizophrenia, who presented with CD in the context of significant depression, suicidal ideation, violence, and self-harm behavior. He perseverated in his belief that he was physically dead and possessed by demons for several weeks. This delusion was reinforced by his religious belief that life was an attribute of God, and by inference, he as a human, was dead. His condition gradually improved over the course of treatment with Divalproex and quetiapine with discussions about the rationale for his belief. Upon discharge, Mr. C. demonstrated awareness of his fixation on death and an ability to redirect himself. DISCUSSION: This case highlights the need to better understand the co occurrence of CD in schizophrenia, their differentiation, the increased risk of violence and self-harm behavior in this presentation, and how specific events and religious factors can influence delusional themes of CD. Pharmacotherapy and aspects of cognitive-behavioral therapy may be effective in ameliorating these symptoms in CD. PMID- 27656158 TI - Helping Others, Warming Yourself: Altruistic Behaviors Increase Warmth Feelings of the Ambient Environment. AB - Altruistic behaviors typically improve the welfare of the recipient at the cost of the performer's resources and energy. Do altruistic performers obtain any positive internal reward from altruistic behaviors? We conducted six experiments to explore whether altruistic behaviors could increase performer's warmth perception of the ambient environment. The first three studies focused on crisis situations. A retrospective field study (Study 1, with Hurricane Sandy) and two laboratory studies (Studies 2a and 2b, with an earthquake scenario) found that people who helped others felt warmer of the ambient environment than people who did not. We extended to daily life situations and found that participants who performed helping behaviors in laboratory (either voluntarily in Study 3a or randomly assigned to in Study 3b) and passers-by who donated to a charity (Study 4) reported warmer perception of the ambient environment than those who did not. These findings suggested an immediate internal reward of altruism. PMID- 27656160 TI - Commentary: Do Bees Play the Producer-Scrounger Game? PMID- 27656161 TI - Facial Cosmetics Exert a Greater Influence on Processing of the Mouth Relative to the Eyes: Evidence from the N170 Event-Related Potential Component. AB - Cosmetic makeup significantly influences facial perception. Because faces consist of similar physical structures, cosmetic makeup is typically used to highlight individual features, particularly those of the eyes (i.e., eye shadow) and mouth (i.e., lipstick). Though event-related potentials have been utilized to study various aspects of facial processing, the influence of cosmetics on specific ERP components remains unclear. The present study aimed to investigate the relationship between the application of cosmetic makeup and the amplitudes of the P1 and N170 event-related potential components during facial perception tasks. Moreover, the influence of visual perception on N170 amplitude, was evaluated under three makeup conditions: Eye Shadow, Lipstick, and No Makeup. Electroencephalography was used to monitor 17 participants who were exposed to visual stimuli under each these three makeup conditions. The results of the present study subsequently demonstrated that the Lipstick condition elicited a significantly greater N170 amplitude than the No Makeup condition, while P1 amplitude was unaffected by any of the conditions. Such findings indicate that the application of cosmetic makeup alters general facial perception but exerts no influence on the perception of low-level visual features. Collectively, these results support the notion that the application of makeup induces subtle alterations in the processing of facial stimuli, with a particular effect on the processing of specific facial components (i.e., the mouth), as reflected by changes in N170 amplitude. PMID- 27656162 TI - The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development. AB - Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus-pituitary-gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success. PMID- 27656163 TI - Aboveground Whitefly Infestation-Mediated Reshaping of the Root Microbiota. AB - Plants respond to various types of herbivore and pathogen attack using well developed defensive machinery designed for self-protection. Infestation from phloem-sucking insects such as whitefly and aphid on plant leaves was previously shown to influence both the saprophytic and pathogenic bacterial community in the plant rhizosphere. However, the modulation of the root microbial community by plants following insect infestation has been largely unexplored. Only limited studies of culture-dependent bacterial diversity caused by whitefly and aphid have been conducted. In this study, to obtain a complete picture of the belowground microbiome community, we performed high-speed and high-throughput next-generation sequencing. We sampled the rhizosphere soils of pepper seedlings at 0, 1, and 2 weeks after whitefly infestation versus the water control. We amplified a partial 16S ribosomal RNA gene (V1-V3 region) by polymerase chain reaction with specific primers. Our analysis revealed that whitefly infestation reshaped the overall microbiota structure compared to that of the control rhizosphere, even after 1 week of infestation. Examination of the relative abundance distributions of microbes demonstrated that whitefly infestation shifted the proteobacterial groups at week 2. Intriguingly, the population of Pseudomonadales of the class Gammaproteobacteria significantly increased after 2 weeks of whitefly infestation, and the fluorescent Pseudomonas spp. recruited to the rhizosphere were confirmed to exhibit insect-killing capacity. Additionally, three taxa, including Caulobacteraceae, Enterobacteriaceae, and Flavobacteriaceae, and three genera, including Achromobacter, Janthinobacterium, and Stenotrophomonas, were the most abundant bacterial groups in the whitefly infested plant rhizosphere. Our results indicate that whitefly infestation leads to the recruitment of specific groups of rhizosphere bacteria by the plant, which confer beneficial traits to the host plant. This study provides a new framework for investigating how aboveground insect feeding modulates the belowground microbiome. PMID- 27656164 TI - All Three Endogenous Quinone Species of Escherichia coli Are Involved in Controlling the Activity of the Aerobic/Anaerobic Response Regulator ArcA. AB - The enteron Escherichia coli is equipped with a branched electron transfer chain that mediates chemiosmotic electron transfer, that drives ATP synthesis. The components of this electron transfer chain couple the oxidation of available electron donors from cellular metabolism (e.g., NADH, succinate, lactate, formate, etc.) to the reduction of electron acceptors like oxygen, nitrate, fumarate, di-methyl-sulfoxide, etc. Three different quinones, i.e., ubiquinone, demethyl-menaquinone and menaquinone, couple the transfer of electrons between the dehydrogenases and reductases/oxidases that constitute this electron transfer chain, whereas, the two-component regulation system ArcB/A regulates gene expression, to allow the organism to adapt itself to the ambient conditions of available electron donors and acceptors. Here, we report that E. coli can grow and adjust well to transitions in the availability of oxygen, with any of the three quinones as its single quinone. In all three 'single-quinone' E. coli strains transitions in the activity of ArcB are observed, as evidenced by changes in the level of phosphorylation of the response regulator ArcA, upon depletion/readmission of oxygen. These results lead us to conclude that all quinol species of E. coli can reduce (i.e., activate) the sensor ArcB and all three quinones oxidize (i.e., de-activate) it. These results also confirm our earlier conclusion that demethyl-menaquinone can function in aerobic respiration. PMID- 27656165 TI - Composition of Ileal Bacterial Community in Grazing Goats Varies across Non rumination, Transition and Rumination Stages of Life. AB - The establishment of gut microbiota is increasingly recognized as a crucial action in neonatal development, host health and productivity. We hypothesized that the ileal microbiome shifted as goats matured, and this colonization process would be associated with host fermentation capacity. To this end, 18 Liuyang black grazing goats were randomly slaughtered at d 0, 7, 28, 42, and 70. Ileal microbiota was profiled by Miseq sequencing of 16S rRNA gene of bacteria, and fermentation capacity [volatile fatty acid, activities of amylase, carboxymethylcellulase (CMCase) and xylanase] was determined using digesta sample. Principal coordinate analysis revealed that each age group harbored its distinct bacteria. Total bacteria copy number and most alpha diversity indexes increased (P < 0.01) from d 0 to 70. At the phylum level, abundances of Cyanobacteria (P = 0.018) and TM7 (P = 0.010) increased linearly, abundances of Bacteroidetes (P = 0.075) and Fibrobacteres (P = 0.076) tended to increase linearly, whist Proteobacteria abundance tended to decline quadratically (P = 0.052) with age. At the genus level, Enterococcus (30.9%), Lactobacillus (32.8%), and Escherichia (2.0%) dominated at d 0, while Prevotella, Butyrivibrio, Ruminococcus, SMB53, and Fibrobacter surged in abundance after day 20. The highest amylase activity was observed at day 42, while xylanase activity increased quadratically (P = 0.002) from days 28 to 70. Correlation analysis indicated that abundances of Bacteroides, Clostridium, Lactobacillus, Propionibacterium, Enterococcus, and p-75-a5 positively correlated with enzyme activity. Collectively, ileal bacteria in grazing goats assemble into distinct communities throughout development, and might participate in the improvement of host fermentation capacity. PMID- 27656167 TI - Insights into the Mechanism of Homeoviscous Adaptation to Low Temperature in Branched-Chain Fatty Acid-Containing Bacteria through Modeling FabH Kinetics from the Foodborne Pathogen Listeria monocytogenes. AB - The psychrotolerant foodborne pathogen Listeria monocytogenes withstands the stress of low temperatures and can proliferate in refrigerated food. Bacteria adapt to growth at low temperatures by increasing the production of fatty acids that increase membrane fluidity. The mechanism of homeoviscous increases in unsaturated fatty acid amounts in bacteria that predominantly contain straight chain fatty acids is relatively well understood. By contrast the analogous mechanism in branched-chain fatty acid-containing bacteria, such as L. monocytogenes, is poorly understood. L. monocytogenes grows at low temperatures by altering its membrane composition to increase membrane fluidity, primarily by decreasing the length of fatty acid chains and increasing the anteiso to iso fatty acid ratio. FabH, the initiator of fatty acid biosynthesis, has been identified as the primary determinant of membrane fatty acid composition, but the extent of this effect has not been quantified. In this study, previously determined FabH steady-state parameters and substrate concentrations were used to calculate expected fatty acid compositions at 30 degrees C and 10 degrees C. FabH substrates 2-methylbutyryl-CoA, isobutyryl-CoA, and isovaleryl-CoA produce the primary fatty acids in L. monocytogenes, i.e., anteiso-odd, iso-even, and iso-odd fatty acids, respectively. In vivo concentrations of CoA derivatives were measured, but not all were resolved completely. In this case, estimates were calculated from overall fatty acid composition and FabH steady-state parameters. These relative substrate concentrations were used to calculate the expected fatty acid compositions at 10 degrees C. Our model predicted a higher level of anteiso lipids at 10 degrees C than was observed, indicative of an additional step beyond FabH influencing fatty acid composition at low temperatures. The potential for control of low temperature growth by feeding compounds that result in the production of butyryl-CoA, the precursor of SCFAs that rigidify the membrane and are incompatible with growth at low temperatures, is recognized. PMID- 27656168 TI - Fragment-Based Whole Cell Screen Delivers Hits against M. tuberculosis and Non tuberculous Mycobacteria. AB - Reactive multi-target 'fragment drugs' represent critical components of current tuberculosis regimens. These compounds, such as pyrazinamide, are old synthetic antimycobacterials that are activated inside Mycobacterium tuberculosis bacilli and are smaller than the usual drug-like, single-target molecules. Based on the success of small 'dirty' drugs in the chemotherapy of tuberculosis, we suggested previously that fragment-based whole cell screens should be introduced in our current antimycobacterial drug discovery efforts. Here, we carried out such a screen and characterized bactericidal activity, selectivity and spectrum of hits we obtained. A library of 1725 fragments was tested at a single concentration for growth inhibitory activity against M. bovis BCG as screening strain and 38 of 116 primary hits were confirmed in dose response analyses to be active against virulent M. tuberculosis. Bacterial kill experiments showed that most hits displayed bactericidal activity at their minimal inhibitory concentration. Cytotoxicity assays established that a large proportion of hits displayed a favorable selectivity index for mammalian cells. Importantly, one third of M. tuberculosis active fragments were also active against M. abscessus and M. avium, two emerging non-tuberculous mycobacterial (NTM) pathogens, opening the opportunity to develop broad spectrum antimycobacterials. Activity determination against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa) bacteria, as well as fungi (Candida albicans, Cryptococcus neoformans) showed only a small overlap indicating a generally narrow spectrum of these novel antimicrobial hits for mycobacteria. In conclusion, we carried out the first fragment-based whole cell screen against bacteria and identified a substantial number of hits with excellent physicochemical properties and dual activity against M. tuberculosis and NTM pathogens. These hits will now be evaluated in animal models of mycobacterial infection to determine whether any of them can be moved forward as a new antimycobacterial fragment drug candidate. PMID- 27656169 TI - The Nucleotide Excision Repair Pathway Protects Borrelia burgdorferi from Nitrosative Stress in Ixodes scapularis Ticks. AB - The Lyme disease spirochete Borrelia burgdorferi encounters a wide range of environmental conditions as it cycles between ticks of the genus Ixodes and its various mammalian hosts. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are potent antimicrobial molecules generated during the innate immune response to infection, however, it is unclear whether ROS and RNS pose a significant challenge to B. burgdorferi in vivo. In this study, we screened a library of B. burgdorferi strains with mutations in DNA repair genes for increased susceptibility to ROS or RNS in vitro. Strains with mutations in the methyl-directed mismatch repair gene mutS1 are hypersensitive to killing by ROS, while strains lacking the nucleotide excision repair (NER) gene uvrB show increased susceptibility to both ROS and RNS. Therefore, mutS1-deficient and uvrB deficient strains were compared for their ability to complete their infectious cycle in Swiss Webster mice and I. scapularis ticks to help identify sites of oxidative and nitrosative stresses encountered by B. burgdorferi in vivo. Both mutS1 and uvrB were dispensable for infection of mice, while uvrB promoted the survival of spirochetes in I. scapularis ticks. The decreased survival of uvrB deficient B. burgdorferi was associated with the generation of RNS in I. scapularis midguts and salivary glands during feeding. Collectively, these data suggest that B. burgdorferi must withstand cytotoxic levels of RNS produced during infection of I. scapularis ticks. PMID- 27656170 TI - Response: Commentary: Zika Virus: the Latest Newcomer. PMID- 27656166 TI - A Review of SHV Extended-Spectrum beta-Lactamases: Neglected Yet Ubiquitous. AB - beta-lactamases are the primary cause of resistance to beta-lactams among members of the family Enterobacteriaceae. SHV enzymes have emerged in Enterobacteriaceae causing infections in health care in the last decades of the Twentieth century, and they are now observed in isolates in different epidemiological settings both in human, animal and the environment. Likely originated from a chromosomal penicillinase of Klebsiella pneumoniae, SHV beta-lactamases currently encompass a large number of allelic variants including extended-spectrum beta-lactamases (ESBL), non-ESBL and several not classified variants. SHV enzymes have evolved from a narrow- to an extended-spectrum of hydrolyzing activity, including monobactams and carbapenems, as a result of amino acid changes that altered the configuration around the active site of the beta -lactamases. SHV-ESBLs are usually encoded by self-transmissible plasmids that frequently carry resistance genes to other drug classes and have become widespread throughout the world in several Enterobacteriaceae, emphasizing their clinical significance. PMID- 27656171 TI - Advances in Research on Epichloe endophytes in Chinese Native Grasses. AB - Epichloe fungal endophytes are broadly found in cool-season grasses. The symbiosis between these grasses and Epichloe may improve the abiotic and biotic resistance of the grass plant, but some Epichloe species produce alkaloids that are toxic for livestock. Therefore, it is important to understand the characteristics of the grass-Epichloe s symbiosis so that the beneficial aspects can be preserved and the toxic effects to livestock can be avoided. Since the 1990s, Chinese researchers have conducted a series of studies on grass-Epichloe symbiosis. In this review, we describe the current state of Epichloe endophyte research in Chinese native grasses. We found that more than 77 species of native grasses in China are associated with Epichloe endophytes. In addition, we review the effects of various Epichloe species on native grass responses to abiotic and biotic stress, phylogeny, and alkaloid production. We provide an overview of the study of Epichloe species on native grasses in China and directions for future research. PMID- 27656174 TI - Genome Sequence of Vibrio parahaemolyticus VP152 Strain Isolated from Penaeus indicus in Malaysia. PMID- 27656173 TI - Enhanced Antibacterial Activity of Acinetobacter baumannii Bacteriophage OABP-01 Endolysin (LysABP-01) in Combination with Colistin. AB - Endolysins are lytic enzymes produced by bacteriophages with their ability to degrade the cell wall of bacterial hosts. Endolysin (LysABP-01) from Acinetobacter baumannii bacteriophage OABP-01 was cloned, overexpressed and characterized. Endolysin LysABP-01 has a globular structure consisting of lysozyme-like (N-acetyl-beta-D-muramidase) catalytic domain. It contains 185 amino acids which correspond to a 21.1 kDa protein. The lytic activity of the recombinant endolysin protein was determined by a plate lysis assay for its ability to lyse the autoclaved cell (crude cell wall) of the different bacterial species. LysABP-01 can degrade the crude cell wall of A. baumannii strains, Escherichia coli and Pseudomonas aeruginosa but not of Staphylococcus aureus. The antibacterial activity of LysABP-01 and its synergism with various antibiotics were tested. The results exhibited elevated antibacterial activity in a combination of the sub-MIC LysABP-01 and colistin. The checkerboard assay for measuring antibiotic synergy of LysABP-01 and colistin was performed. This combination was synergistic against various drug-resistant strains of A. baumannii (FIC index < 0.5). In summary, our study highlights the ability of LysABP-01 endolysin to hydrolyze the A. baumannii cell wall and its synergistic interaction with colistin. PMID- 27656172 TI - Validation of a High-Throughput Multiplex Genetic Detection System for Helicobacter pylori Identification, Quantification, Virulence, and Resistance Analysis. AB - Helicobacter pylori (H. pylori) infection is closely related to various gastroduodenal diseases. Virulence factors and bacterial load of H. pylori are associated with clinical outcomes, and drug-resistance severely impacts the clinical efficacy of eradication treatment. Existing detection methods are low throughput, time-consuming and labor intensive. Therefore, a rapid and high throughput method is needed for clinical diagnosis, treatment, and monitoring for H. pylori. High-throughput Multiplex Genetic Detection System (HMGS) assay was established to simultaneously detect and analyze a set of genes for H. pylori identification, quantification, virulence, and drug resistance by optimizing the singlet-PCR and multiple primers assay. Twenty-one pairs of chimeric primers consisted of conserved and specific gene sequences of H. pylori tagged with universal sequence at the 5' end were designed. Singlet-PCR assay and multiple primers assay were developed to optimize the HMGS. The specificity of HMGS assay was evaluated using standard H. pylori strains and bacterial controls. Six clinical isolates with known genetic background of target genes were detected to assess the accuracy of HMGS assay. Artificial mixed pathogen DNA templates were used to evaluate the ability to distinguish mixed infections using HMGS assay. Furthermore, gastric biopsy specimens with corresponding isolated strains were used to assess the capability of HMGS assay in detecting biopsy specimens directly. HMGS assay was specific for H. pylori identification. HMGS assay for H. pylori target genes detection were completely consistent with the corresponding genetic background. Mixed infection with different drug-resistant isolates of H. pylori could be distinguished by HMGS assay. HMGS assay could efficiently diagnose H. pylori infection in gastric biopsy specimens directly. HMGS assay is a rapid and high throughput method for the simultaneous identification and quantification of H. pylori, analysis of virulence and drug resistance in both isolated strains and biopsy specimens. It could also be used to distinguish the mixed infection with different resistant genotype strains. Furthermore, HMGS could detect H. pylori infection in gastric biopsy specimens directly. PMID- 27656175 TI - Investigating the Inactivation Mechanism of Bacillus subtilis Spores by High Pressure CO2. AB - The objective of this study was to investigate the inactivation mechanism of Bacillus subtilis spores by high pressure CO2 (HPCD) processing. The spores of B. subtilis were subjected to heat at 0.1 MPa or HPCD at 6.5-20 MPa, and 64-86 degrees C for 0-120 min. The germination, the permeability of inner membrane (IM) and cortex, the release of pyridine-2, 6-dicarboxylic acid (DPA), and changes in the morphological and internal structures of spores were investigated. The HPCD treated spores did not lose heat resistance and their DPA release was lower than the inactivation, suggesting that spores did not germinate during HPCD. The flow cytometry analysis suggested that the permeability of the IM and cortex of HPCD treated spores was increased. Furthermore, the DPA of the HPCD-treated spores were released in parallel with their inactivation and the fluorescence photomicrographs showed that these treated spores were stained by propidium iodide, ensuring that the permeability of IM of spores was increased by HPCD. The scanning electron microscopy photomicrographs showed that spores were crushed into debris or exhibited a hollowness on the surface, and the transmission electron microscopy photomicrographs exhibited an enlarged core, ruptured and indistinguishable IM and a loss of core materials in the HPCD-treated spores, indicating that HPCD damaged the structures of the spores. These findings suggested that HPCD inactivated B. subtilis spores by directly damaging the structure of the spores, rather than inducing germination of the spores. PMID- 27656176 TI - Marinobacter Dominates the Bacterial Community of the Ostreococcus tauri Phycosphere in Culture. AB - Microalgal-bacterial interactions are commonly found in marine environments and are well known in diatom cultures maintained in laboratory. These interactions also exert strong effects on bacterial and algal diversity in the oceans. Small green eukaryote algae of the class Mamiellophyceae (Chlorophyta) are ubiquitous and some species, such as Ostreococcus spp., are particularly important in Mediterranean coastal lagoons, and are observed as dominant species during phytoplankton blooms in open sea. Despite this, little is known about the diversity of bacteria that might facilitate or hinder O. tauri growth. We show, using rDNA 16S sequences, that the bacterial community found in O. tauri RCC4221 laboratory cultures is dominated by gamma-proteobacteria from the Marinobacter genus, regardless of the growth phase of O. tauri RCC4221, the photoperiod used, or the nutrient conditions (limited in nitrogen or phosphorous) tested. Several strains of Marinobacter algicola were detected, all closely related to strains found in association with taxonomically distinct organisms, particularly with dinoflagellates and coccolithophorids. These sequences were more distantly related to M. adhaerens, M. aquaeoli and bacteria usually associated to euglenoids. This is the first time, to our knowledge, that distinct Marinobacter strains have been found to be associated with a green alga in culture. PMID- 27656177 TI - The Two Sets of DMSO Respiratory Systems of Shewanella piezotolerans WP3 Are Involved in Deep Sea Environmental Adaptation. AB - Dimethyl sulfoxide (DMSO) is an abundant methylated sulfur compound in deep sea ecosystems. However, the mechanism underlying DMSO-induced reduction in benthic microorganisms is unknown. Shewanella piezotolerans WP3, which was isolated from a west Pacific deep sea sediment, can utilize DMSO as the terminal electron acceptor. In this study, two putative dms gene clusters [type I (dmsEFA1B1G1H1) and type II (dmsA2B2G2H2)] were identified in the WP3 genome. Genetic and physiological analyses demonstrated that both dms gene clusters were functional and the transcription of both gene clusters was affected by changes in pressure and temperature. Notably, the type I system is essential for WP3 to thrive under in situ conditions (4 degrees C/20 MPa), whereas the type II system is more important under high pressure or low temperature conditions (20 degrees C/20 MPa, 4 degrees C/0.1 MPa). Additionally, DMSO-dependent growth conferred by the presence of both dms gene clusters was higher than growth conferred by either of the dms gene clusters alone. These data collectively suggest that the possession of two sets of DMSO respiratory systems is an adaptive strategy for WP3 survival in deep sea environments. We propose, for the first time, that deep sea microorganisms might be involved in global DMSO/DMS cycling. PMID- 27656180 TI - Cross-Talk between the Aeromonas hydrophila Type III Secretion System and Lateral Flagella System. AB - Aeromonas hydrophila is responsible for aeromonad septicaemia in fish, and gastroenteritis and wound infections in humans. The type III secretion system (T3SS) is utilized by aeromonads to inject protein effectors directly into host cells. One of the major genetic regulators of the T3SS in several bacterial species is the AraC-like protein ExsA. Previous studies have suggested a link between T3SS regulation and lateral flagella expression. The aim of this study was to determine the genetic regulation of the T3SS and its potential interaction with the lateral flagella system in A. hydrophila. To investigate the genes encoding the T3SS regulatory components exsA, exsD, exsC, and exsE were mutated and the activities of the T3SS promoters were measured in wild type and mutant backgrounds demonstrating a regulatory network. The Exs proteins were shown to interact with each other by BACTH assay and Far-Western Blot. The findings suggested a regulatory cascade in which ExsE was bound to the chaperone protein ExsC. When ExsC was free it sequestered the anti-activator ExsD thus stopping the inhibition of the T3SS master regulator ExsA allowing T3SS expression. The T3SS regulatory components were also shown to affect the expression of the lateral flagella system. The activities of the lateral flagella promoters were shown to be repressed by the absence of ExsD and ExsE, suggesting that the T3SS master regulator ExsA was a negative regulator of the lateral flagella system. PMID- 27656179 TI - Longitudinal Comparison of Antibiotic Resistance in Diarrheagenic and Non pathogenic Escherichia coli from Young Tanzanian Children. AB - Enteroaggregative, enteropathogenic, and enterotoxigenic Escherichia coli contribute significantly to the burden of diarrheal infections particularly in developing countries. Antibiotic resistance is increasingly common among bacterial pathogens including pathogenic E. coli. We assessed the relationship between pathogenic E. coli carriage and resistance to six antibiotics in E. coli isolated from young children in rural Tanzania. We surveyed temporal stability in antibiotic resistance in 2492 E. coli isolated from fecal samples obtained from young children in rural Tanzania collected over a 6 months period. Approximately half of the 377 children sampled were exposed to an azithromycin mass treatment program for trachoma control and half resided in control villages. Children were sampled at baseline, 1-, 3-, and 6 months following azithromycin treatment. We compared resistance to six antibiotics in pathogenic and non-pathogenic strains at the population level, within fecal specimens, and within individuals over time using chi-square tests, paired odds ratios, and logistic regression, respectively. Resistance to ampicillin and trimethoprim/sulfamethoxazole was highly prevalent (>65%). Resistance to 5 of 6 antibiotics tested and multi-drug resistance occurred more frequently in pathogenic isolates (p <= 0.001) within fecal specimens and overall. Azithromycin mass treatment exposure was significantly associated with increased odds of carriage of isolates resistant to erythromycin (OR 3.64, p < 0.001) and trimethoprim/sulfamethoxazole (OR 1.60, p < 0.05). Pathogenic isolates were approximately twice as likely to be resistant to erythromycin, ampicillin, or trimethoprim/sulfamethoxazole compared to non pathogenic isolates from the same fecal specimen. The potential linkage between resistance and virulence in E. coli suggests hygiene and sanitation interventions aimed at reducing disease burden could play a role in controlling transmission of antibiotic resistance. PMID- 27656181 TI - Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives. AB - The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients. PMID- 27656182 TI - Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon. AB - The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food derived antigenic challenge. These lymphoid organs encompass Peyer's patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTbeta) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID- 27656183 TI - Identification of Two Subgroups of Type I IFNs in Perciforme Fish Large Yellow Croaker Larimichthys crocea Provides Novel Insights into Function and Regulation of Fish Type I IFNs. AB - Like mammals, fish possess an interferon regulatory factor (IRF) 3/IRF7-dependent type I IFN responses, but the exact mechanism by which IRF3/IRF7 regulate the type I IFNs remains largely unknown. In this study, we identified two type I IFNs in the Perciforme fish large yellow croaker Larimichthys crocea, one of which belongs to the fish IFNd subgroup and the other is assigned to a novel subgroup of group I IFNs in fish, tentatively termed IFNh. The two IFN genes are constitutively expressed in all examined tissues, but with varied expression levels. Both IFN genes can be rapidly induced in head kidney and spleen tissues by polyinosinic-polycytidylic acid. The recombinant IFNh was shown to be more potent to trigger a rapid induction of the antiviral genes MxA and protein kinase R than the IFNd, suggesting that they may play distinct roles in regulating early antiviral immunity. Strikingly, IFNd, but not IFNh, could induce the gene expression of itself and IFNh through a positive feedback loop mediated by the IFNd-dependent activation of IRF3 and IRF7. Furthermore, our data demonstrate that the induction of IFNd can be enhanced by the dimeric formation of IRF3 and IRF7, while the IFNh expression mainly involves IRF3. Taken together, our findings demonstrate that the IFN responses are diverse in fish and are likely to be regulated by distinct mechanisms. PMID- 27656178 TI - Molecular Biology and Infection of Hepatitis E Virus. AB - Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus. PMID- 27656184 TI - The Protective Effect against Extracellular Histones Afforded by Long-Pentraxin PTX3 as a Regulator of NETs. AB - Pentraxin 3 (PTX3) is a soluble pattern recognition molecule that plays critical roles in innate immunity. Its fundamental functions include recognition of microbes, activation of complement cascades, and opsonization. The findings that PTX3 is one of the component proteins in neutrophil extracellular traps (NETs) and binds with other NET proteins imply the importance of PTX3 in the NET mediated trapping and killing of bacteria. As NETs play certain critically important host-protective roles, aberrant NET production results in tissue damage. Extracellular histones, the main source of which is considered to be NETs, are mediators of septic death due to their cytotoxicity toward endothelial cells. PTX3 protects against extracellular histones-mediated cytotoxicity through coaggregation. In addition to the anti-bacterial roles performed in coordination with other NET proteins, PTX3 appears to mitigate the detrimental effect of over activated NETs. A better understanding of the role of the PTX3 complexes in NETs would be expected to lead to new strategies for maintaining a healthy balance between the helpful bactericidal and undesirable detrimental activities of NETs. PMID- 27656186 TI - RNA-seq Analysis of Overexpressing Ovine AANAT Gene of Melatonin Biosynthesis in Switchgrass. AB - Melatonin serves important functions in the promotion of growth and anti-stress regulation by efficient radical scavenging and regulation of antioxidant enzyme activity in various plants. To investigate its regulatory roles and metabolism pathways, the transcriptomic profile of overexpressing the ovine arylalkylamine N acetyltransferase (oAANAT) gene, encoding the penultimate enzyme in melatonin biosynthesis, was compared with empty vector control using RNA-seq in switchgrass, a model plant of cellulosic ethanol conversion. The 85.22 million high quality reads that were assembled into 135,684 unigenes were generated by Illumina sequencing for transgenic oAANAT switchgrass with an average sequence length of 716 bp. A total of 946 differentially expression genes in transgenic line comparing to control switchgrass, including 737 up-regulated and 209 down regulated genes, were mainly enriched with two main functional patterns of melatonin identifying by gene ontology analysis: the growth regulator and stress tolerance. Furthermore, KEGG maps indicated that the biosynthetic pathways of secondary metabolite (phenylpropanoids, flavonoids, steroids, stilbenoid, diarylheptanoid, and gingerol) and signaling pathways (MAPK signaling pathway, estrogen signaling pathway) were involved in melatonin metabolism. This study substantially expands the transcriptome information for switchgrass and provides valuable clues for identifying candidate genes involved in melatonin biosynthesis and elucidating the mechanism of melatonin metabolism. PMID- 27656187 TI - Stress-Inducible Expression of an F-box Gene TaFBA1 from Wheat Enhanced the Drought Tolerance in Transgenic Tobacco Plants without Impacting Growth and Development. AB - E3 ligase plays an important role in the response to many environment stresses in plants. In our previous study, constitutive overexpression of an F-box protein gene TaFBA1 driven by 35S promoter improved the drought tolerance in transgenic tobacco plants, but the growth and development in transgenic plants was altered in normal conditions. In this study, we used stress-inducible promoter RD29A instead of 35S promoter, as a results, the stress-inducible transgenic tobacco plants exhibit a similar phenotype with wild type (WT) plants. However, the drought tolerance of the transgenic plants with stress-inducible expressed TaFBA1 was enhanced. The improved drought tolerance of transgenic plants was indicated by their higher seed germination rate and survival rate, greater biomass and photosynthesis than those of WT under water stress, which may be related to their greater water retention capability and osmotic adjustment. Moreover, the transgenic plants accumulated less reactive oxygen species, kept lower MDA content and membrane leakage under water stress, which may be related to their higher levels of antioxidant enzyme activity and upregulated gene expression of some antioxidant enzymes. These results suggest that stress induced expression of TaFBA1 confers drought tolerance via the improved water retention and antioxidative compete ability. Meanwhile, this stress-inducible expression strategy by RD29A promoter can minimize the unexpectable effects by 35S constitutive promoter on phenotypes of the transgenic plants. PMID- 27656188 TI - Transcriptomics and Metabolite Analysis Reveals the Molecular Mechanism of Anthocyanin Biosynthesis Branch Pathway in Different Senecio cruentus Cultivars. AB - The cyanidin (Cy), pelargonidin (Pg), and delphinidin (Dp) pathways are the three major branching anthocyanin biosynthesis pathways that regulate flavonoid metabolic flux and are responsible for red, orange, and blue flower colors, respectively. Different species have evolved to develop multiple regulation mechanisms that form the branched pathways. In the current study, five Senecio cruentus cultivars with different colors were investigated. We found that the white and yellow cultivars do not accumulate anthocyanin and that the blue, pink, and carmine cultivars mainly accumulate Dp, Pg, and Cy in differing densities. Subsequent transcriptome analysis determined that there were 43 unigenes encoding anthocyanin biosynthesis genes in the blue cultivar. We also combined chemical and transcriptomic analyses to investigate the major metabolic pathways that are related to the observed differences in flower pigmentation in the series of S. cruentus. The results showed that mutations of the ScbHLH17 and ScCHI1/2 coding regions abolish anthocyanin formation in the white and the yellow cultivars; the competition of the ScF3'H1, ScF3'5'H, and ScDFR1/2 genes for naringenin determines the differences in branching metabolic flux of the Cy, Dp, and Pg pathways. Our findings provide new insights into the regulation of anthocyanin branching and also supplement gene resources (including ScF3'5 'H, ScF3'H, and ScDFRs) for flower color modification of ornamentals. PMID- 27656185 TI - Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination. AB - Adoptive cellular therapy (ACT) is a form of immunotherapy whereby antigen specific T cells are isolated or engineered, expanded ex vivo, and transferred back to patients. Clinical benefit after ACT has been obtained in treatment of infection, various hematological malignancies, and some solid tumors; however, due to poor functionality and persistence of the transferred T cells, the efficacy of ACT in the treatment of most solid tumors is often marginal. Hence, much effort is undertaken to improve T cell function and persistence in ACT and significant progress is being made. Herein, we will review strategies to improve ACT success rates in the treatment of cancer and infection. We will deliberate on the most favorable phenotype for the tumor-specific T cells that are infused into patients and on how to obtain T cells bearing this phenotype by applying novel ex vivo culture methods. Moreover, we will discuss T cell function and persistence after transfer into patients and how these factors can be manipulated by means of providing costimulatory signals, cytokines, blocking antibodies to inhibitory molecules, and vaccination. Incorporation of these T cell stimulation strategies and combinations of the different treatment modalities are likely to improve clinical response rates further. PMID- 27656190 TI - The Tomato Spotted Wilt Virus Genome Is Processed Differentially in its Plant Host Arachis hypogaea and its Thrips Vector Frankliniella fusca. AB - Thrips-transmitted tospoviruses are economically important viruses affecting a wide range of field and horticultural crops worldwide. Tomato spotted wilt virus (TSWV) is the type member of the Tospovirus genus with a broad host range of more than 900 plant species. Interactions between these viruses and their plant hosts and insect vectors via RNAi pathways are likely a key determinant of pathogenicity. The current investigation, for the first time, compares biogenesis of small RNAs between the plant host and insect vector in the presence or absence of TSWV. Unique viral small interfering RNA (vsiRNA) profiles are evident for Arachis hypogaea (peanut) and Frankliniella fusca (thrips vector) following infection with TSWV. Differences between vsiRNA profiles for these plant and insect species, such as the relative abundance of 21 and 22 nt vsiRNAs and locations of alignment hotspots, reflect the diverse siRNA biosynthesis pathways of their respective kingdoms. The presence of unique vsiRNAs in F. fusca samples indicates that vsiRNA generation takes place within the thrips, and not solely through uptake via feeding on vsiRNAs produced in infected A. hypogaea. The study also shows key vsiRNA profile differences for TSWV among plant families, which are evident in the case of A. hypogaea, a legume, and members of Solanaceae (S. lycopersicum and Nicotiana benthamiana). Distinctively, overall small RNA (sRNA) biogenesis in A. hypogaea is markedly affected with an absence of the 24 nt sRNAs in TSWV-infected plants, possibly leading to wide-spread molecular and phenotypic perturbations specific to this species. These findings add significant information on the host-virus-vector interaction in terms of RNAi pathways and may lead to better crop and vector specific control strategies. PMID- 27656189 TI - Morphological Structure and Transcriptome Comparison of the Cytoplasmic Male Sterility Line in Brassica napus (SaNa-1A) Derived from Somatic Hybridization and Its Maintainer Line SaNa-1B. AB - SaNa-1A is a novel cytoplasmic male sterility (CMS) line in Brassica napus derived from progenies of somatic hybrids between B.napus and Sinapis alba, and SaNa-1B is the corresponding maintainer line. In this study, phenotypic differences of floral organs between CMS and the maintainer lines were observed. By microscope observation in different anther developmental stages of two lines, we found the anther development in SaNa-1A was abnormal since the tetrad stage, and microspore development was ceased during the uninucleate stage. Transcriptomic sequencing for floral buds of sterile and fertile plants were conducted to elucidate gene expression and regulation caused by the alien chromosome and cytoplasm from S. alba. Clean tags obtained were assembled into 195,568 unigenes, and 7811 unigenes distributed in the metabolic and protein synthesis pathways were identified with significant expression differences between two libraries. We also observed that genes participating in carbon metabolism, tricarboxylic acid cycle, oxidative phosphorylation, oxidation reduction system, pentatricopeptide repeat, and anther development were downregulated in the sterile line. Some of them are candidates for researches on the sterility mechanism in the CMS material, fertility restoration, and improvement of economic traits in the maintainer line. Further research on the tags with expressional specificity in the fertile line would be helpful to explore desirable agronomic traits from wild species of rapeseed. PMID- 27656192 TI - Rhizobial Inoculation Increases Soil Microbial Functioning and Gum Arabic Production of 13-Year-Old Senegalia senegal (L.) Britton, Trees in the North Part of Senegal. AB - Rhizobial inoculation has been widely used in controlled conditions as a substitute for chemical fertilizers to increase plants growth and productivity. However, very little is known about such effects on mature trees in natural habitats. In this study, we investigated the effect of rhizobial inoculation on soil total microbial biomass, mineral nitrogen content, potential CO2 respiration, fluorescein diacetate (FDA), acid phosphatase activities, and gum arabic production by 13-year-old Senegalia senegal (synonym: Acacia senegal) under natural conditions in the north part of Senegal during two consecutive years. Rhizobial inoculation was performed at the beginning of the rainy season (July) for both years with a cocktail of four strains (CIRADF 300, CIRADF 301, CIRADF 302, and CIRADF 303). Rhizospheric soils were collected in both dry and rainy seasons to a depth of 0-25 cm under uninoculated and inoculated trees. Trees were tapped in November (beginning of dry season) using traditional tools. Gum arabic was harvested every 15 days from December to March. The results obtained from both years demonstrated that rhizobial inoculation increased significantly the percentage of trees producing gum arabic, gum arabic production per tree, soil microbial biomass, FDA, and acid phosphatase activities. However, there was no significant effect on C mineralization and mineral nitrogen (N) content. Gum arabic production was positively correlated to rainfall, soil microbial biomass, and mineral nitrogen content. Our results showed a positive effect of rhizobial inoculation on soil microbial functioning and gum arabic production by mature S. senegal trees. These important findings deserve to be conducted in several contrasting sites in order to improve gum arabic production and contribute to increase rural population incomes. PMID- 27656191 TI - A Mechanical Model to Interpret Cell-Scale Indentation Experiments on Plant Tissues in Terms of Cell Wall Elasticity and Turgor Pressure. AB - Morphogenesis in plants is directly linked to the mechanical elements of growing tissues, namely cell wall and inner cell pressure. Studies of these structural elements are now often performed using indentation methods such as atomic force microscopy. In these methods, a probe applies a force to the tissue surface at a subcellular scale and its displacement is monitored, yielding force-displacement curves that reflect tissue mechanics. However, the interpretation of these curves is challenging as they may depend not only on the cell probed, but also on neighboring cells, or even on the whole tissue. Here, we build a realistic three dimensional model of the indentation of a flower bud using SOFA (Simulation Open Framework Architecture), in order to provide a framework for the analysis of force-displacement curves obtained experimentally. We find that the shape of indentation curves mostly depends on the ratio between cell pressure and wall modulus. Hysteresis in force-displacement curves can be accounted for by a viscoelastic behavior of the cell wall. We consider differences in elastic modulus between cell layers and we show that, according to the location of indentation and to the size of the probe, force-displacement curves are sensitive with different weights to the mechanical components of the two most external cell layers. Our results confirm most of the interpretations of previous experiments and provide a guide to future experimental work. PMID- 27656193 TI - Characterization of CIPK Family in Asian Pear (Pyrus bretschneideri Rehd) and Co expression Analysis Related to Salt and Osmotic Stress Responses. AB - Asian pear (Pyrus bretschneideri) is one of the most important fruit crops in the world, and its growth and productivity are frequently affected by abiotic stresses. Calcineurin B-like interacting protein kinases (CIPKs) as caladium sensor protein kinases interact with Ca(2+)-binding CBLs to extensively mediate abiotic stress responses in plants. Although the pear genome sequence has been released, little information is available about the CIPK genes in pear, especially in response to salt and osmotic stresses. In this study, we systematically identified 28 CIPK family members from the sequenced pear genome and analyzed their organization, phylogeny, gene structure, protein motif, and synteny duplication divergences. Most duplicated PbCIPKs underwent purifying selection, and their evolutionary divergences accompanied with the pear whole genome duplication. We also investigated stress -responsive expression patterns and co-expression networks of CIPK family under salt and osmotic stresses, and the distribution of stress-related cis-regulatory elements in promoter regions. Our results suggest that most PbCIPKs could play important roles in the abiotic stress responses. Some PbCIPKs, such as PbCIPK22, -19, -18, -15, -8, and -6 can serve as core regulators in response to salt and osmotic stresses based on co expression networks of PbCIPKs. Some sets of genes that were involved in response to salt did not overlap with those in response to osmotic responses, suggesting the sub-functionalization of CIPK genes in stress responses. This study revealed some candidate genes that play roles in early responses to salt and osmotic stress for further characterization of abiotic stress responses medicated by CIPKs in pear. PMID- 27656194 TI - Editorial: The Human Gutome: Nutrigenomics of Host-Microbiome Interactions. PMID- 27656196 TI - Adverse reaction to metal debris in a painful hemiarthroplasty of the hip. AB - Adverse reaction to metal debris (ARMD) in total hip arthroplasty surgery is a well-known problem. We present the case of a unipolar hemiarthroplasty requiring revision within 18 months of insertion secondary to an adverse reaction to metal debris. This case demonstrates a rare cause for failure of a hemiarthroplasty following a fragility fracture. We feel that ARMD should be considered in all cases where pain and dysfunction in the presence of any hip prosthesis cannot be explained by routine investigations. PMID- 27656197 TI - An alternative technique for direct implantation of an anomalous left coronary artery arising from the pulmonary artery with complex coronary arteries. AB - A 2-month-old patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) underwent an alternative repair involving coronary transfer with the bay window technique because of the very short left main coronary trunk. This procedure is a clinically relevant and feasible technique for ALCAPA with such a delicate coronary artery anomaly. PMID- 27656198 TI - Laparoscopic removal of a gallbladder remnant in a patient with severe biliary pancreatitis. AB - Many surgeons opt to perform subtotal cholecystectomy to limit duct injuries in difficult cases. In these cases, however, there is a risk for the gallbladder remnant to become diseased. In these cases, a completion cholecystectomy is necessary.Although technically challenging, the laparoscopic approach to completion cholecystectomy is feasible and safe, when performed by surgeons with advanced laparoscopic experience. PMID- 27656199 TI - Extract the Relational Information of Static Features and Motion Features for Human Activities Recognition in Videos. AB - Both static features and motion features have shown promising performance in human activities recognition task. However, the information included in these features is insufficient for complex human activities. In this paper, we propose extracting relational information of static features and motion features for human activities recognition. The videos are represented by a classical Bag-of Word (BoW) model which is useful in many works. To get a compact and discriminative codebook with small dimension, we employ the divisive algorithm based on KL-divergence to reconstruct the codebook. After that, to further capture strong relational information, we construct a bipartite graph to model the relationship between words of different feature set. Then we use a k-way partition to create a new codebook in which similar words are getting together. With this new codebook, videos can be represented by a new BoW vector with strong relational information. Moreover, we propose a method to compute new clusters from the divisive algorithm's projective function. We test our work on the several datasets and obtain very promising results. PMID- 27656200 TI - R2-Based Multi/Many-Objective Particle Swarm Optimization. AB - We propose to couple the R2 performance measure and Particle Swarm Optimization in order to handle multi/many-objective problems. Our proposal shows that through a well-designed interaction process we could maintain the metaheuristic almost inalterable and through the R2 performance measure we did not use neither an external archive nor Pareto dominance to guide the search. The proposed approach is validated using several test problems and performance measures commonly adopted in the specialized literature. Results indicate that the proposed algorithm produces results that are competitive with respect to those obtained by four well-known MOEAs. Additionally, we validate our proposal in many-objective optimization problems. In these problems, our approach showed its main strength, since it could outperform another well-known indicator-based MOEA. PMID- 27656195 TI - Structural biology of the macroautophagy machinery. AB - Macroautophagy is a conserved degradative process mediated through formation of a unique double-membrane structure, the autophagosome. The discovery of autophagy related (Atg) genes required for autophagosome formation has led to the characterization of approximately 20 genes mediating this process. Recent structural studies of the Atg proteins have provided the molecular basis for their function. Here we summarize the recent progress in elucidating the structural basis for autophagosome formation. PMID- 27656201 TI - A Modified MinMax k-Means Algorithm Based on PSO. AB - The MinMax k-means algorithm is widely used to tackle the effect of bad initialization by minimizing the maximum intraclustering errors. Two parameters, including the exponent parameter and memory parameter, are involved in the executive process. Since different parameters have different clustering errors, it is crucial to choose appropriate parameters. In the original algorithm, a practical framework is given. Such framework extends the MinMax k-means to automatically adapt the exponent parameter to the data set. It has been believed that if the maximum exponent parameter has been set, then the programme can reach the lowest intraclustering errors. However, our experiments show that this is not always correct. In this paper, we modified the MinMax k-means algorithm by PSO to determine the proper values of parameters which can subject the algorithm to attain the lowest clustering errors. The proposed clustering method is tested on some favorite data sets in several different initial situations and is compared to the k-means algorithm and the original MinMax k-means algorithm. The experimental results indicate that our proposed algorithm can reach the lowest clustering errors automatically. PMID- 27656202 TI - Select and Cluster: A Method for Finding Functional Networks of Clustered Voxels in fMRI. AB - Extracting functional connectivity patterns among cortical regions in fMRI datasets is a challenge stimulating the development of effective data-driven or model based techniques. Here, we present a novel data-driven method for the extraction of significantly connected functional ROIs directly from the preprocessed fMRI data without relying on a priori knowledge of the expected activations. This method finds spatially compact groups of voxels which show a homogeneous pattern of significant connectivity with other regions in the brain. The method, called Select and Cluster (S&C), consists of two steps: first, a dimensionality reduction step based on a blind multiresolution pairwise correlation by which the subset of all cortical voxels with significant mutual correlation is selected and the second step in which the selected voxels are grouped into spatially compact and functionally homogeneous ROIs by means of a Support Vector Clustering (SVC) algorithm. The S&C method is described in detail. Its performance assessed on simulated and experimental fMRI data is compared to other methods commonly used in functional connectivity analyses, such as Independent Component Analysis (ICA) or clustering. S&C method simplifies the extraction of functional networks in fMRI by identifying automatically spatially compact groups of voxels (ROIs) involved in whole brain scale activation networks. PMID- 27656203 TI - ELM Meets Urban Big Data Analysis: Case Studies. AB - In the latest years, the rapid progress of urban computing has engendered big issues, which creates both opportunities and challenges. The heterogeneous and big volume of data and the big difference between physical and virtual worlds have resulted in lots of problems in quickly solving practical problems in urban computing. In this paper, we propose a general application framework of ELM for urban computing. We present several real case studies of the framework like smog related health hazard prediction and optimal retain store placement. Experiments involving urban data in China show the efficiency, accuracy, and flexibility of our proposed framework. PMID- 27656204 TI - Molecular Diversity of Sapovirus Infection in Outpatients Living in Nanjing, China (2011-2013). AB - Aim. To gain insight into the molecular diversity of sapovirus in outpatients with acute gastroenteritis in Nanjing, China. Methods. The specimens from outpatients clinically diagnosed as acute gastroenteritis were detected by real time PCR; RT-PCR was then performed to amplify part of VP1 sequences. The PCR products were cloned into pGEM-T Easy vector and bidirectionally sequenced. All sequences were edited and analyzed. A phylogenetic tree was drawn with the MEGA 5.0 software. Results. Between 2011 and 2013, 16 sapovirus positive cases were confirmed by real-time PCR. The infected cases increased from two in 2011 and six in 2012 to eight in 2013. The majority was children and the elderly (15, 93.75%) and single infections (15, 93.75%). Of the 16 real-time positive specimens, 14 specimens had PCR products and the analysis data of the 14 nucleic sequences showed that there was one GI genogroup with four genotypes, two GI.2 in 2011, three GI.2, and one GI.1 in 2012 and one GI.2, three GI.1, two GI.3, and two GI.5 in 2013. Conclusion. Our data confirmed continuous existing of GI genogroup and GI.2 genotype from 2011 to 2013 in Nanjing and the successive appearance of different genotypes from outpatients with gastroenteritis. PMID- 27656205 TI - Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection. AB - Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV infected patients. Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers. Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ? 6) (HR = 4.63, P = 0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71, P = 0.014), accompanying cirrhosis (HR = 19.34, P = 0.004), and low platelet count (HR = 13.97, P = 0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13, P = 0.012) and low albumin level (HR = 9.17, P = 0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality. Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality. PMID- 27656206 TI - Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials. AB - Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55-0.75) and OS (HR 0.83; 95%-CI, 0.76-0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95% CI, 1.41-3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs. PMID- 27656207 TI - Differences in miRNA and mRNA Profile of Papillary Thyroid Cancer Variants. AB - Papillary thyroid cancer (PTC) can be divided into classical variant of PTC (cPTC), follicular variant of PTC (fvPTC), and tall cell variant (tcPTC). These variants differ in their histopathology and cytology; however, their molecular background is not clearly understood. Our results shed some new light on papillary thyroid cancer biology as new direct miRNA-gene regulations are discovered. The Cancer Genome Atlas (TCGA) 466 thyroid cancer samples were studied in parallel datasets to discover potential miRNA-mRNA regulations. Additionally, miRNAs and genes differentiating PTC variants (cPTC, fvPTC, and tcPTC) were indicated. Putative miRNA regulatory pairs were discovered: hsa-miR 146b-5p with PHKB and IRAK1, hsa-miR-874-3p with ITGB4 characteristic for classic PTC samples, and hsa-miR-152-3p with TGFA characteristic for follicular variant PTC samples. MiRNA-mRNA regulations discovery opens a new perspective in understanding of PTC biology. Furthermore, our successful pipeline of miRNA-mRNA regulatory pathways discovery could serve as a universal tool to find new miRNA mRNA regulations, also in different datasets. PMID- 27656208 TI - Baseline Body Composition in Prepubertal Short Stature Children with Severe and Moderate Growth Hormone Deficiency. AB - Objective. To compare body composition parameters in short children with severe versus moderate and no growth hormone deficiency (GHD). Design and Method. 61 children (40 boys) were studied. Height SDS, BMI Z-score, waist/height ratio (W/HtR), and body composition parameters (BIA) as fat tissue (FAT%), fat-free mass (FFM%), predicted muscle mass (PMM%), and total body water (TBW%) were evaluated. GH secretion in the overnight profile and two stimulation tests and insulin-like growth factor 1 (IGF-1) level were measured. Results. Overall, in 16 (26%) moderate (7.0 > peak GH < 10 ng/mL) and in 11 (18%) severe (GH <= 7.0 ng/mL) GHD was diagnosed. In children with sGHD BMI Z-score, W/HtR and FAT% were significantly higher, while FFM%, PMM%, and TBW% were significantly lower versus mGHD and versus noGHD subgroups. No significant differences between mGHD and noGHD were found. There were no differences in height SDS and IGF-1 SDS between evaluated subgroups. Night GH peak level correlated significantly with FAT%, FFM%, PMM%, and TBW%, (p < 0.05) in the entire group. Conclusions. Only sGHD is associated with significant impairment of body composition. Body composition analysis may be a useful tool in distinguishing between its severe and moderate form of GHD. PMID- 27656209 TI - 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis. AB - Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4 PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-alpha and IL-1beta, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID- 27656210 TI - X-Linked Adrenal Hypoplasia Congenita in a Boy due to a Novel Deletion of the Entire NR0B1 (DAX1) and MAGEB1-4 Genes. AB - X-linked Adrenal Hypoplasia Congenita (AHC) is caused by deletions or point mutations in the NR0B1 (DAX1) gene. We present a boy with AHC who came at the age of 25 days in a severe state due to prolonged vomiting and progressive dehydration. Laboratory studies showed prominent hyponatremia and hyperkaliemia but not hypoglycemia. Primary adrenal insufficiency was confirmed with low serum cortisol levels and high plasma ACTH levels. Hydrocortisone therapy combined with saline and glucose infusions was started immediately after blood collection. Two exons of the NR0B1 (DAX1) gene were impossible to amplify using the standard PCR method. Array CGH was used to confirm the putative copy-number variation of NR0B1 (DAX1) revealing a novel hemizygous deletion encompassing the entire NR0B1 (DAX1) gene together with the MAGEB genes. This genetic defect was also present in heterozygosity in the patient's mother. We show that NR0B1 (DAX1) gene analysis is important for confirmation of AHC diagnosis and highlights the role of genetic counseling in families with AHC patients, particularly those with X chromosome microdeletions, covering more than NR0B1 (DAX1) alone. We hope that further clinical follow-up of this patient and his family will shed a new light on the role of MAGEB genes. PMID- 27656211 TI - Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma. AB - Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of <=13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients. PMID- 27656212 TI - Fracture Resistance of Endodontically Treated Maxillary Premolars Restored by Various Direct Filling Materials: An In Vitro Study. AB - The aim of this study is to compare the effect of various restorative materials on fracture resistance in maxillary premolars. Premolars (n = 64) with no restorations or cracks were selected. MOD cavities were prepared considering the buccolingual width to be equal to half of the intercuspal distance. The specimens were randomly divided into 8 groups, 8 specimens each: group A intact teeth, group B unfilled cavity, group C composite made by oblique layering technique, group D composite with 2 mm cusp coverage, group E bulk-filled posterior composite, group F glass-ionomer, group G amalgam, and group H composite with proximal boxes. The specimens were subjected to an axial compression load with the mean values of fracture resistance in group A: 1289 N, group B: 181.75 N, group C: 445.38 N, group D: 645.88 N, group E: 355.13 N, group F: 352.00 N, group G: 191.38 N, and group H: 572.00 N. There was no significant difference between groups B and G, between C and D, E, and F, and between group D and H. All other measurements were statistically significant. We conclude that composite restoration with cusp coverage is the most ideal nonprosthetic solution for endodontically treated teeth. Cusp coverage increases the fracture resistance compared to the conventional cavity design. PMID- 27656213 TI - Unintended Pregnancy in Ethiopia: Community Based Cross-Sectional Study. AB - Introduction. Unintended pregnancy is defined as a pregnancy which is a sum of mistimed pregnancy (pregnancy wanted at a later time) and unwanted pregnancy (pregnancy which is not wanted at all). Unintended pregnancy is a global public health problem and its sequels are major causes for maternal and neonatal morbidity and mortality with its effect to maternal metal illness as well. Objective. To determine the prevalence and associated factors of unintended pregnancy in Debre Birhan town, northeast of Ethiopia, in 2014. Method. Community based cross-sectional study and questionnaire developed from Ethiopian demographic health survey 2011. Participants were 690 currently pregnant mothers. Association of unintended pregnancy with factors was measured with bivariate and multivariate logistic regressions. Result. In this study unintended pregnancy is found to be 23.5%. Being formerly married and never married, distance to the nearest health facility >80 minutes, gravidity >5, 1-2 parity, and partner disagreement on desired number of children are the variables significantly associated with unintended pregnancy. Conclusion. Significant proportion of unintended pregnancy is found in the study area. To minimize unintended pregnancy concerned bodies should work on the identified factors, so we can minimize maternal and neonatal morbidity and mortality and keep the health of the family specifically and country in general. PMID- 27656214 TI - Transplanted Endothelial Progenitor Cells Improve Ischemia Muscle Regeneration in Mice by Diffusion Tensor MR Imaging. AB - Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. Diffusion tensor imaging (DTI) was applied to detect the architectural organization of skeletal muscle. This study investigated the feasibility and accuracy of using the DTI to evaluate effectiveness of EPCs treatment. Mouse bone marrow-derived EPCs were isolated, cultured, characterized, and transplanted to hindlimb ischemia mice model. DTI was performed on the hindlimb at postischemia time points. The edema regions of diffusion restriction (high signal in diffusion weighted imaging) were decreased in the ischemic muscle of EPCs treated mice after 14 days compared with the controls. These results from DTI show the lower apparent diffusion coefficient and eigenvalues (lambda1, lambda2, and lambda3) and the higher fractional anisotropy and fiber counts of ischemic muscle on 7 and 14 days after EPCs treatment compared to the controls. There was a significant correlation between fiber counts calculated by DTI and survival fibers evaluated by histological section (r = 0.873, P < 0.01). Our study demonstrated that the time frame for muscle fiber regeneration after EPCs transplantation was significantly shortened in vivo. DTI could be a useful tool for noninvasive evaluation of muscle tissue damage and repair in animal models and patient with ischemic diseases. PMID- 27656215 TI - Dynamic Tracking of Injected Mesenchymal Stem Cells after Myocardial Infarction in Rats: A Serial 7T MRI Study. AB - Purpose. To track the fate of micron-sized particles of iron oxide (MPIO) labeled mesenchymal stem cells (MSCs) in vivo in a rat myocardial infarction model using 7T magnetic resonance imaging (MRI) scanner. Materials and Methods. Male MSCs (2 * 10(6)/50 MUL) dual-labeled with MPIO and CM-DiI were injected into the infarct periphery 7 days after myocardial infarction (MI). The control group received cell-free media injection. The temporal stem cell location, signal intensity, and cardiac function were dynamically assessed using a 7T MRI at 24 h before transplantation (baseline), 3 days, 2 weeks, and 4 weeks after transplantation, respectively. Results. MR hypointensities caused by MPIOs were observed on T2(*) weighted images at all time points after MSCs injection. Cine-MRI showed that MSCs moderated progressive left ventricular remodeling. Double staining for iron and CD68 revealed that most of the iron-positive cells were CD68-positive macrophages. Real-time PCR for rat SRY gene showed the number of survival MSCs considerably decreased after transplantation. MSC-treated hearts had significantly increased capillary density in peri-infarct region and lower cardiomyocytes apoptosis and fibrosis formation. Conclusions. Iron particles are not a reliable marker for in vivo tracking the long-term fate of MSCs engraftment. Despite of poor cell retention, MSCs moderate left ventricular remodeling after MI. PMID- 27656217 TI - Clinical Efficacy and Meta-Analysis of Stem Cell Therapies for Patients with Brain Ischemia. AB - Objective. Systematic review and meta-analysis to observe the efficacy and safety of stem cell transplantation therapy in patients with brain ischemia. Methods. We searched Cochrane Library, PubMed, Ovid, CBM, CNKI, WanFang, and VIP Data from its inception to December 2015, to collect randomized controlled trials (RCT) of stem cell transplantation for the ischemic stroke. Two authors independently screened the literature according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias. Thereafter, meta-analysis was performed. Results. Sixteen studies and eighteen independent treatments were included in the current meta-analysis. The results based upon the pooled mean difference from baseline to follow-up points showed that the stem cell transplantation group was superior to the control group with statistical significance in the neurologic deficits score (NIHSS, MD = 1.57; 95% CI, 0.64 2.51; I (2) = 57%; p = 0.001), motor function (FMA, MD = 4.23; 95% CI, 3.08-5.38; I (2) = 0%; p < 0.00001), daily life ability (Barthel, MD = 8.37; 95% CI, 4.83 11.91; I (2) = 63%; p < 0.00001), and functional independence (FIM, MD = 8.89; 95% CI, 4.70-13.08; I (2) = 79%; p < 0.0001). Conclusions. It is suggested that the stem cell transplantation therapy for patients with brain ischemic stroke can significantly improve the neurological deficits and daily life quality, with no serious adverse events. However, higher quality and larger data studies are required for further investigation to support clinical application of stem cell transplantation. PMID- 27656216 TI - Biological Effects of Culture Substrates on Human Pluripotent Stem Cells. AB - In recent years, as human pluripotent stem cells (hPSCs) have been commonly cultured in feeder-free conditions, a number of cell culture substrates have been applied or developed. However, the functional roles of these substrates in maintaining hPSC self-renewal remain unclear. Here in this review, we summarize the types of these substrates and their effect on maintaining hPSC self-renewal. Endogenous extracellular matrix (ECM) protein expression has been shown to be crucial in maintaining hPSC self-renewal. These ECM molecules interact with integrin cell-surface receptors and transmit their cellular signaling. We discuss the possible effect of integrin-mediated signaling pathways on maintaining hPSC self-renewal. Activation of integrin-linked kinase (ILK), which transmits ECM integrin signaling to AKT (also known as protein kinase B), has been shown to be critical in maintaining hPSC self-renewal. Also, since naive pluripotency has been widely recognized as an alternative pluripotent state of hPSCs, we discuss the possible effects of culture substrates and integrin signaling on naive hPSCs based on the studies of mouse embryonic stem cells. Understanding the role of culture substrates in hPSC self-renewal and differentiation enables us to control hPSC behavior precisely and to establish scalable or microfabricated culture technologies for regenerative medicine and drug development. PMID- 27656218 TI - Comparison of Stemness and Gene Expression between Gingiva and Dental Follicles in Children. AB - The aim of this study was to compare the differential gene expression and stemness in the human gingiva and dental follicles (DFs) according to their biological characteristics. Gingiva (n = 9) and DFs (n = 9) were collected from 18 children. Comparative gene expression profiles were collected using cDNA microarray. The expression of development, chemotaxis, mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSs) related genes was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Histological analysis was performed using hematoxylin-eosin and immunohistochemical staining. Gingiva had greater expression of genes related to keratinization, ectodermal development, and chemotaxis whereas DFs exhibited higher expression levels of genes related to tooth and embryo development. qRT PCR analysis showed that the expression levels of iPSc factors including SOX2, KLF4, and C-MYC were 58.5 +/- 26.3, 12.4 +/- 3.5, and 12.2 +/- 1.9 times higher in gingiva and VCAM1 (CD146) and ALCAM (CD166) were 33.5 +/- 6.9 and 4.3 +/- 0.8 times higher in DFs. Genes related to MSCs markers including CD13, CD34, CD73, CD90, and CD105 were expressed at higher levels in DFs. The results of qRT-PCR and IHC staining supported the microarray analysis results. Interestingly, this study demonstrated transcription factors of iPS cells were expressed at higher levels in the gingiva. Given the minimal surgical discomfort and simple accessibility, gingiva is a good candidate stem cell source in regenerative dentistry. PMID- 27656219 TI - Nutritional Status and Intestinal Parasite in School Age Children: A Comparative Cross-Sectional Study. AB - Background. The objectives of this study were to determine the burden of underweight and intestinal parasitic infection in the urban and rural elementary school children. Methods. A comparative cross-sectional study design was conducted. Binary logistic regression was used to identify the determinants of malnutrition or intestinal parasites. Two independent samples' t-test was used to identify the effect of malnutrition on school performance or hemoglobin level. Results. A total of 2372 students were included. Quarters (24.8%) of school children were underweight. Underweight was associated with sex [adjusted odds ratio (AOR) 0.61; 95% CI = 0.47-0.78], age [AOR = 0.21; 95% CI = 0.16-0.28], intestinal parasitic infection [AOR 2.67; 95% CI = 2-3.55], and family size [AOR 23; 95% CI = 17.67-30.02]. The prevalence of intestinal parasite among school children was 61.7% [95% CI = 60%-64%]. Shoe wearing practice [AOR 0.71; 95% CI = 0.58-0.87], personal hygiene [AOR 0.8; 95% CI = 0.65-0.99], availability of latrine [AOR 0.34; 95% CI = 0.27-0.44], age [AOR 0.58; 95% CI = 0.48-0.7], habit of eating raw vegetables [AOR 3.71; 95% CI = 3.01-4.46], and family size [AOR 1.96; 95% CI = 1.57-2.45] were the predictors of intestinal parasitic infection. PMID- 27656221 TI - Evaluation of immunogenicity and protective efficacy of a liposome containing Brucella abortus S19 outer membrane protein in BALB/c mice. AB - The use of liposome as an adjuvant and a vaccine carrier has been cited previously in the literature. It has also been shown to be effective in enhancing the immunogenicity of vaccine candidates. BALB/c mice immunized subcutaneously with outer membrane protein (OMP) of Brucella abortus S19 vaccine strain entrapped in a commercial cationic liposome (S19-OMP-liposome) for vaccine delivery, showed enhanced protection (P<0.05) compared to groups of mice inoculated with S19 OMP alone, S19 live B. abortus vaccine and liposome alone, when challenged intra-peritoneally with virulent B. abortus strain 544 at 30 days post-immunization (DPI). The S19-OMP-liposome preparation was found to be safer compared to the live B. abortus S19 vaccine at 15 days post challenge (DPC), as evidenced by the significant difference in spleen weight between S19-OMP liposome, S19 OMP and S19 live as well as the liposome control groups (P<0.01). Antibody isotype response profiles of the experimental groups indicated that the immune response was Th1 cell mediated. The protective advantage conferred to mice immunized with S19-OMP entrapped in liposome over those immunized with the live B. abortus S19 version, could probably be related to the significantly different response of IgG2b at 30 DPI (P<0.01), IgG2a (P<0.01), IgG2b (P<0.01) and IgG3 (P<0.05) at the DPC stages, respectively. PMID- 27656222 TI - Evaluation of the efficacy of a new oil-based adjuvant ISA 61 VG FMD vaccine as a potential vaccine for cattle. AB - Foot-and-mouth disease is an important viral disease of cloven-hoofed animals. Inactivated whole particle virus vaccines are still widely used in prophylactic vaccination campaigns. The choice of adjuvant is a very important factor in enhancing immune responses and the efficacy of inactivated vaccines. Montanide ISA 61 VG is a new ready-to-use mineral oil-based adjuvant developed by SEPPIC Inc. (SEPPIC, France) with high-potential immune responses needed for clinical protection against FMD infection. In this study, we compared the efficacy of two FMD vaccines either formulated with the new oil-based adjuvant ISA 61 VG and saponin, or with aluminum hydroxide gel and saponin. Both vaccines contained the same antigen payloads of O2010/IR. Two groups of 15 naive cattle received a single vaccination with different doses (full dose, 1/3 dose and 1/9 dose) to calculate their PD50 (50% protective dose) after being challenged with the homologous virulent virus. The mean neutralizing antibody titer was determined at 0, 7, 14 and 21 days after vaccination, measured by a micro neutralization test. The new vaccine improved humoral immune responses by 19%, while inducing a higher geometric mean. The titer for neutralizing antibodies was 2.91 log10 compared to the alum-gel based adjuvant vaccine which was 2.44 log10 (P-value=0.1782). The new vaccine showed a PD50 value of 10.05 as compared to a PD50 value of 4.171, respectively. According to the results, the FMD vaccine formulated with the new oil adjuvant, ISA 61 VG, shows potential as an alternative vaccine for routine and emergency vaccinations in the FMD enzootic region. PMID- 27656223 TI - Influence of naturally unilateral cryptorchidism on the histomorphometry of the testes and daily sperm production in West African Dwarf goats. AB - Quantitative histology of the descended testis of unilateral cryptorchid bucks was compared with testis of normal bucks to evaluate the reproductive potentials of the scrotal testis in unilateral cryptorchids, using light microscopy techniques. The contralateral scrotal testes of the unilateral cryptorchids and the testes of the normal bucks contained profiles of seminiferous epithelium and each showed histological evidence of normal activity. The mean heights, lengths, lumen diameter, diameter of the seminiferous tubules were significantly higher in the contralateral scrotal testes when compared to the retained testes of the unilateral cryptorchid bucks (P<0.05). Population of spermatogenic cells per testis, and ratio of germ cells to Sertoli cells were not significantly different between both groups. The percentage of the testes occupied by various germ cells did not differ between the scrotal testis of the cryptorchid bucks and those of the normal bucks. The volume occupied by the seminiferous tubules and Leydig cells in the contralateral scrotal testis of the unilateral cryptorchid bucks were significantly greater than those of the testis of normal bucks (P<0.05). From the findings, it appears that the spermatogenic efficiency of the scrotal testes of the unilateral cryptorchid bucks was significantly higher than those of the normal bucks. PMID- 27656220 TI - Evaluation of Risk Factors for Antibiotic Resistance in Patients with Nosocomial Infections Caused by Pseudomonas aeruginosa. AB - Background. Pseudomonas aeruginosa (P. aeruginosa) is resistant to various antibiotics and can cause serious nosocomial infections with high morbidity and mortality. In this clinical study, we investigated the risk factors in patients who were diagnosed with P. aeruginosa-related nosocomial infection. Methods. A retrospective case control study including patients with P. aeruginosa-related nosocomial infection. Patients who were resistant to any of the six antibiotics (imipenem, meropenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and ceftazidime) constituted the study group. Results. One hundred and twenty isolates were isolated. Various risk factors were detected for each antibiotic in the univariate analysis. In the multivariate analysis, previous cefazolin use was found as an independent risk factor for the development of imipenem resistance (OR = 3.33; CI 95% [1.11-10.0]; p = 0.03), whereas previous cerebrovascular attack (OR = 3.57; CI 95% [1.31-9.76]; p = 0.01) and previous meropenem use (OR = 4.13; CI 95% [1.21-14.07]; p = 0.02) were independent factors for the development of meropenem resistance. For the development of resistance to ciprofloxacin, hospitalization in the neurology intensive care unit (OR = 4.24; CI 95% [1.5 11.98]; p = 0.006) and mechanical ventilator application (OR = 11.7; CI 95% [2.24 61.45]; p = 0.004) were independent risk factors. Conclusion. The meticulous application of contact measures can decrease the rate of nosocomial infections. PMID- 27656224 TI - Detection of dermatophytes in healthy companion dogs and cats in eastern India. AB - In recent times increasing occurrence of dermatophytosis, especially among the school children in eastern India was evidenced along with increased tendency of keeping companion animals such as dogs and cats. This study was undertaken to detect the occurrence of dermatophytes with antifungal susceptibility among the companion animals. A total of 1501 healthy companion animals comprising 1209 dogs and 292 cats belonged to individual owners in and around Kolkata (West Bengal, India) were examined for the evidence of dermatophytosis during 2011-2013. The collected samples were subjected to direct examination by standard KOH mount technique. The samples were inoculated into both Sabouraud dextrose agar (SDA) with 0.05% chloramphenicol and 0.5% cycloheximide and dermatophyte test medium (DTM). Each of the fungal isolate was identified based upon its colony characteristics and hyphal and conidial cells it produced. Antifungal susceptibility of the isolates was tested by broth micro dilution assay using fluconazole, ketoconazole, itraconazole, miconazole, griseofulvin and amphotericin-B antifungals. Among the 1209 samples from dogs and 292 samples from cats, 253 (20.93%) and 109 (37.33%) samples were positive for dermatophytes by direct examination. Three identified species of dermatophytes with predominant occurrence were Microsporum canis, Microsporum gypseum and Trichophyton mentagrophytes. Ketoconazole (0.06-0.5 ugm/ml), itraconazole (0.03-0.5 ugm/ml) and amphotericin-B (0.03-0.5 ugm/ml) showed lowest MIC values against M. canis, T. mentagrophytes and M. gypseum, respectively. This is the first systemic report of dermatophytes in healthy companion animals with large numbers of samples in India. PMID- 27656225 TI - Techniques for augmentation of exogenous DNA uptake by ovine spermatozoa. AB - Sperm mediated gene transfer can be an inexpensive and simple method in animal transgenesis; however its efficiency is poor, mainly due to the spermatozoa's lesser uptake of exogenous DNA. In the present study, the effects of lipofection and other augmentation techniques, such as sperm freezing and spermatozoa treatment with triton X100 and DMSO, on exogenous DNA uptake by sheep spermatozoa and motility of sperms with plasmid uptake were evaluated. In the first experiment, ram sperms were incubated with a complex of rhodamine labeled plasmid (p-EGFP) and Lipofectamine 2000(TM). In the second, spermatozoa were treated with Triton X-100(TM) or DMSO or were frozen without cryoprotectant. The results indicated that there was no significant difference (P<0.05) in the transfection rates and in the uptake intensity of lipofected sperms with 300 and 600 ng of plasmid in comparison with control group, i.e. transfected without lipofectamine. Furthermore, lipofection could not improve sperm motility during true plasmid uptake. Almost all of triton X100 treated and frozen-thawed spermatozoa had absorbed foreign DNA, though all were immotile. In spermatozoa treated with 0.1% DMSO, plasmid absorption rate (69.40%) was significantly higher (P<0.05) than untreated spermatozoa (57.80%), but sperm motility was not significantly different from control group. In conclusion, lipofectamine((r)) 2000 could neither improve transfection rate, nor support motility in transfected sperms. The methods inducing membrane disruption like, freeze-thaw and triton X100 treatment, can be used in ICSI-sperm mediated gene transfer without the need for sperm selection, provided that they cause no damage to sperm nucleus. PMID- 27656226 TI - Permethrin-induced oxidative damage in liver of rainbow trout (Oncorhynchus mykiss) and its attenuation by vitamin C. AB - The objective of this study was to investigate the propensity of permethrin (PTN) to induce oxidative stress and changes in enzyme activities in liver of rainbow trout and its possible attenuation by vitamin C. Forty-eight fish were randomly assigned to 1 of 6 treatment groups and their livers were used for liver perfusion method: control (0 ugL(-1) permethrin and 0 mgL(-1) vitamin C), PTN 0.16 (0.16 ugL(-1) permethrin), PTN-0.32 (0.32 ugL(-1) permethrin), PTN-0.64 (0.64 ugL(-1) permethrin), Vit. C (17.2 mgL(-1) vitamin C), and PTN-0.64 + Vit. C (0.64 ugL(-1) permethrin and 17.2 mgL(-1) vitamin C). Results obtained showed that permethrin significantly (P<0.05) increased ALT, AST and LDH activities in the liver perfusion medium and malondialdehyde (MDA) level in liver tissue. The values of reduced glutathione (GSH) and total antioxidant capacity (FRAP) in the liver tissue were significantly decreased due to permethrin administration. Pearson's correlation analysis revealed a positive correlation between MDA concentration and ALT, AST and LDH activities in the permethrin groups, suggesting that the enhanced lipid peroxidation may be linked to hepatic damage caused by permethrin. On the other hand, treatment with vitamin C in the PTN-0.64 + Vit. C group increased the values of GSH and FRAP, and decreased the level of MDA and the activities of hepatic enzymes, when compared to the PTN-0.64 group. The present study revealed that vitamin C could ameliorate permethrin-induced oxidative damage by decreasing lipid peroxidation and altering antioxidant defense system in liver of rainbow trout. PMID- 27656227 TI - Comparative evaluation between chitosan and atorvastatin on serum lipid profile changes in hyperlipidemic cats. PMID- 27656228 TI - Molecular investigation of Coxiella burnetii infections in aborted sheep in eastern Turkey. AB - Q fever is a zoonotic disease that occurs worldwide and is caused by the obligate intracellular bacterium Coxiella burnetii. The aim of this study was to investigate the presence of C. burnetii infection in aborted sheep in eastern Turkey using PCR. A total of 200 fetuses were collected from aborted sheep belonging to 200 herds in different locations in the eastern part of Turkey. Foetal organ samples such as liver, spleen, lung and stomach were taken and the DNA was purified from two hundred pooled samples. PCR analysis of C. burnetii presence in infected organs was performed, and 4 samples (2%) were found positive. In addition, the pooled organ suspensions were inoculated to embryonated chicken eggs, and PCR analysis of yolk sacs showed C. burnetii DNA in 5 samples (2.5%). This study shows that C. burnetii infection has an important role in sheep abortions in eastern Anatolia region. PMID- 27656229 TI - Cervical mucus characteristics and hormonal status at insemination of Holstein cows. AB - The present study was carried out to characterize the cervical mucus (CM) collected when inseminating Holstein cows and to relate the secretion pattern with pregnancy. The mucus was collected from mid-cervix of 64 cows with spontaneus estrus (SE) and induced estrus (IE). The quantity, pattern and consistency of the mucus, pH, arborization patterns and the sperm motility were observed. The levels of progesterone and estradiol 17beta in serum were also determined. Pregnancy detection was performed by means of transrectal ultrasonography 60 days after insemination. Mucous secretion of cows with SE was significantly different from those with IE, showing a lower degree of crystallization (SE 2.00; IE 2.75) and a lower level of steroid hormones (P4: SE 0.17 ng/ml and IE 0.33 ng/ml (t 1.99547 alpha 0.05); E2: SE 30.95 pg/ml and IE 47.76 pg/ml (t 1.99495 alpha 0.05). Progesterone level was significantly lower and estrogen significantly higher in pregnant cows (P) in relation to that observed in non pregnant females (N) (P4: P 0.20 ng/ml and N 0.44 ng/ml (t 1.99602 alpha 0.05); E2: P 54.77 pg/ml and N 40.75 pg/ml (t 1.99505 alpha 0.05). In conclusion pregnancy was associated with acopious, clear and watery discharge (similar to egg white), with an arborization degree of 2.25, presence of atypical fern leaves together with rosette formations and needles or thorns on rails due to low levels of progesterone accompanied by high concentrations of estrogens. PMID- 27656230 TI - Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods. AB - Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups. PMID- 27656231 TI - Morphological and morphometric study of early-cleavage mice embryos resulting from in vitro fertilization at different cleavage stages after vitrification. AB - The aim of this study was to examine the possible morphological and morphometric changes resulting from vitrification of embryos at the cleavage stage. In this study, 30 mice early-cleavage embryos at different stages of cleavage, resulting from in vitro fertilization (IVF) techniques, were examined before and after vitrification. Digital images were taken from embryos before and after vitrification. Zona pellucida thickness, differences in zona pellucida thickness, and diameter and volume of blastomeres and embryos as morphometric parameters and current rating of appearance of embryos as morphological parameters, have been studied. According to our findings, there were significant mean differences in all morphometric parameters of the two groups except in the zona pellucid thickness (P<=0.05). With regard to the morphological parameter, the decrease in embryo quality was observed but it was not significant. According to the results, although little quantitative change observed is not necessarily synonymous with harmful intracellular damage, it seems that it is better to examine vitrification method more accurately. Because by making subtle changes in concentration and type of consumed solutions or techniques used, the changes may be minimized. PMID- 27656232 TI - Successful management of an equine carpal chip fracture by intra-articularly injected adipose-derived stromal vascular fraction after arthroscopic removal. AB - Carpal chip fractures are common causes of lameness in racehorses. Due to disadvantages in surgical management, adjuvant treatment modalities are usually necessary. Adipose-derived stem cells (ADSCs) have the potential to differentiate into other cell types including bone and cartilage cells. Adipose-derived stromal vascular fraction (SVF) is produced during ADSCs isolation from adipose tissue. The purpose of this report was to present the successful management of a grade III chip fracture in the right carpus of a 5-year-old Thoroughbred gelding by intra-articularly injected autologous SVF one month after the arthroscopic removal of the fracture. This treatment resulted in lameness improvement and short rehabilitation period to previous racing activities. High performance levels and no recurrent injuries were recorded during a twenty month follow-up period. PMID- 27656233 TI - Administration of recombinant human granulocyte colony-stimulating factor (rhG CSF) for the intracranial hemorrhage in two dogs: a case report. AB - Two dogs with generalized seizures were evaluated. The dogs were diagnosed with traumatic intracranial hemorrhages based on the history, neurological examinations, and magnetic resonance imaging (MRI) of the brain. Treatment was started with oxygen, prednisolone and anticonvulsant agents. No further seizure activity was observed after treatment in both dogs, however cushing reflex was detected in case 1 and a left-sided hemi-paresis was detected in case 2. Further supportive treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) was attempted. No abnormal signs were noted in either of the dogs and no recurrence was noted 16 and 14 months later, in case 1 and 2, respectively. These cases indicate that a combination of rhG-CSF treatment with previous therapy could be used in dogs with traumatic brain injury. PMID- 27656234 TI - The Role of Interferon Lambda 3 Genetic Polymorphisms in Response to Interferon Therapy in Chronic Hepatitis B Patients: An Updated Meta-Analysis. AB - CONTEXT: Polymorphisms of the interferon lambda 3 (IFNL3) gene have been proposed to be associated with drug-induced clearance of the hepatitis C virus (HCV). However, the role of IFNL3 polymorphisms in the prediction of treatment on chronic hepatitis B (CHB) patients have yielded controversial results. The aim of this study was to clarify the role of IFNL3 polymorphisms (rs12979860, rs8099917, and rs12980275) in the treatment response of CHB patients to interferon (IFN). EVIDENCE ACQUISITION: EMBASE and PUBMED/MEDLINE were searched to identify relevant studies from January 2009 to March 2015. The search used the keyword "interferon lambda 3" or "IFNL3," combined with the following terms: "interferon therapy," "hepatitis," and "polymorphisms." Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were used to assess the strength of the associations between the polymorphisms and the response to IFN therapy. RESULTS: Nine studies of 1602 CHB patients receiving IFN treatment were included. Under the random-effects model, patients expressing the variant rs12980275 showed a significantly increased response to IFN therapy (OR = 2.85; 95% CI = 1.14 - 4.60). In the subgroup analyses by antiviral agents, the patients carrying the rs8099917T allele in the IFN-only treatment group showed a significantly increased response to IFN therapy (OR for the dominant model = 2.03; 95% CI = 1.24 - 3.31), whereas those in the mixed treatment group showed a significantly decreased response (OR for the dominant model = 0.30; 95% CI = 0.10 - 0.90). CONCLUSIONS: This study supports the idea that the IFNL3 gene is an important predictor of the response of CHB patients to IFN therapy. PMID- 27656236 TI - The Induction of Apoptosis in A375 Malignant Melanoma Cells by Sutherlandia frutescens. AB - Sutherlandia frutescens is a medicinal plant indigenous to Southern Africa and is commonly known as the "cancer bush." This plant has traditionally been used for the treatment of various ailments, although it is best known for its claims of activity against "internal" cancers. Here we report on its effect on melanoma cells. The aim of this study was to investigate whether an extract of S. frutescens could induce apoptosis in the A375 melanoma cell line and to outline the basic mechanism of action. S. frutescens extract induced apoptosis in A375 cells as evidenced by morphological features of apoptosis, phosphatidylserine exposure, nuclear condensation, caspase activation, and the release of cytochrome c from the mitochondria. Studies in the presence of a pan-caspase inhibitor allude to caspase-independent cell death, which appeared to be mediated by the apoptosis inducing factor. Taken together, the results of this study show that S. frutescens extract is effective in inducing apoptosis in malignant melanoma cells and indicates that further in vivo mechanistic studies may be warranted. PMID- 27656235 TI - Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic. AB - Nootropics or smart drugs are well-known compounds or supplements that enhance the cognitive performance. They work by increasing the mental function such as memory, creativity, motivation, and attention. Recent researches were focused on establishing a new potential nootropic derived from synthetic and natural products. The influence of nootropic in the brain has been studied widely. The nootropic affects the brain performances through number of mechanisms or pathways, for example, dopaminergic pathway. Previous researches have reported the influence of nootropics on treating memory disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Those disorders are observed to impair the same pathways of the nootropics. Thus, recent established nootropics are designed sensitively and effectively towards the pathways. Natural nootropics such as Ginkgo biloba have been widely studied to support the beneficial effects of the compounds. Present review is concentrated on the main pathways, namely, dopaminergic and cholinergic system, and the involvement of amyloid precursor protein and secondary messenger in improving the cognitive performance. PMID- 27656237 TI - The Efficacy and Safety of Chinese Herbal Decoction in Type 2 Diabetes: A 5-Year Retrospective Study. AB - Background. The study was designed to assess the efficacy and safety of Chinese herbal decoction in treating outpatients with T2DM. Methods. All patients enrolled received decoction for at least 6 months. The primary outcome was the control rate of HbA1c and the change in HbA1c. FPG, 2hPG, HOMA-IR, and HOMA-beta were also collected and evaluated. Results. The control rates after treatment at months 6, 12, 18, 24, 36, 48, and 60 were 45.07%, 52.78%, 47.22%, 45.83%, 50.00%, 57.14%, and 40.00%. Multiple linear regression showed the change of HbA1c has a significant relationship with the baseline HbA1c and duration of DM and BMI (p < 0.05). Both FPG and 2hPG levels significantly decreased compared to the baseline (p < 0.05). Chinese herbal decoction also improved islet cell function with decreased HOMA-IR and increased HOMA-beta (p < 0.05). 19 and 4 subjects deactivated the antidiabetes drugs or insulin, respectively, after taking decoction. One subject developed DKD and one developed DPN, and another subject showed abnormal liver function which was irrelevant to decoction treatment. Conclusions. Chinese herbal decoction significantly enhanced the hypoglycemic action and had certain effect on protecting islet cell function. As a candidate diabetes therapy, it may reduce the use of antidiabetes drugs and slow the progression to diabetes complications. PMID- 27656238 TI - Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model. AB - In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon gamma [IFNgamma], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORgamma) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA. PMID- 27656239 TI - Effervescent Granules Prepared Using Eucommia ulmoides Oliv. and Moso Bamboo Leaves: Hypoglycemic Activity in HepG2 Cells. AB - Eucommia ulmoides Oliv. (E. ulmoides Oliv.) and moso bamboo (Phyllostachys pubescens) leaves are used as folk medicines in central-western China to treat diabetes. To investigate the hypoglycemic activity of the effervescent granules prepared using E. ulmoides Oliv. and moso bamboo leaves (EBEG) in HepG2 cells, EBEG were prepared with 5% of each of polysaccharides and chlorogenic acids from moso bamboo and E. ulmoides Oliv. leaves, respectively. HepG2 cells cultured in a high-glucose medium were classified into different groups. The results displayed EBEG-treated cells showed better glucose utilization than the negative controls; thus, the hypoglycemic effect of EBEG was much greater than that of granules prepared using either component alone, thereby indicating that this effect was due to a synergistic action of the components. Further, glucose consumption levels in the cells treated with EBEG (156.35% at 200 MUg/mL) and the positive controls (metformin, 162.29%; insulin, 161.52%) were similar. Thus, EBEG exhibited good potential for use as a natural antidiabetic agent. The hypoglycemic effect of EBEG could be due to the synergistic action of polysaccharides from the moso bamboo leaves and chlorogenic acids from E. ulmoides Oliv. leaves via the inhibition of alpha-glucosidase and glucose-6 phosphate displacement enzyme. PMID- 27656240 TI - To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory. AB - Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p < 0.05), and the coefficient was 0.178 (p < 0.05); also they were related with five flavors (p < 0.05), and the coefficient was 0.145 (p < 0.05); they were not related with channel tropism (p > 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs. PMID- 27656241 TI - Diosgenin and 5-Methoxypsoralen Ameliorate Insulin Resistance through ER alpha/PI3K/Akt-Signaling Pathways in HepG2 Cells. AB - To determine the effects and the underlying mechanism of diosgenin (DSG) and 5 methoxypsoralen (5-MOP), two main active components in the classical Chinese prescription Hu-Lu-Ba-Wan (HLBW), on insulin resistance, HepG2 cells were incubated in medium containing insulin. Treatments with DSG, 5-MOP, and their combination were performed, respectively. The result showed that the incubation of HepG2 cells with high concentration insulin markedly decreased glucose consumption and glycogen synthesis. However, treatment with DSG, 5-MOP, or their combination significantly reversed the condition and increased the phosphorylated expression of estrogen receptor-alpha (ERalpha), sarcoma (Src), Akt/protein kinase B, glycogen synthase kinase-3beta (GSK-3beta), and the p85 regulatory subunit of phosphatidylinositol 3-kinase p85 (PI3Kp85). At the transcriptional level, expression of the genes mentioned above also increased except for the negative regulation of GSK-3beta mRNA. The increased expression of glucose transport-4 (GLUT-4) was meanwhile observed through immunofluorescence. Nevertheless, the synergistic effect of DSG and 5-MOP on improving glycometabolism was not obvious in the present study. These results suggested that DSG and 5-MOP may improve insulin resistance through an ER-mediated PI3K/Akt activation pathway which may be a new strategy for type 2 diabetes mellitus, especially for women in an estrogen-deficient condition. PMID- 27656244 TI - Polar Pattern Formation in Driven Filament Systems Require Non-Binary Particle Collisions. AB - Living matter has the extraordinary ability to behave in a concerted manner, which is exemplified throughout nature ranging from the self-organisation of the cytoskeleton to flocks of animals [1-4]. The microscopic dynamics of constituents have been linked to the system's meso- or macroscopic behaviour in silico via the Boltzmann equation for propelled particles [5-10]. Thereby, simplified binary collision rules between the constituents had to be assumed due to the lack of experimental data. We report here experimentally determined binary collision statistics by studying the recently introduced molecular system, the high density actomyosin motility assay [11-13]. We demonstrate that the alignment effect of the binary collision statistics is too weak to account for the observed ordering transition. The transition density for polar pattern formation decreases quadratically with filament length, which indicates that multi-filament collisions drive the observed ordering phenomenon and that a gas-like picture cannot explain the transition of the system to polar order. The presented findings demonstrate that the unique properties of biological active matter systems require a description that goes well beyond a gas-like picture developed in the framework of kinetic theories. PMID- 27656243 TI - An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity. AB - Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension) than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted. PMID- 27656242 TI - PI3K-GLUT4 Signal Pathway Associated with Effects of EX-B3 Electroacupuncture on Hyperglycemia and Insulin Resistance of T2DM Rats. AB - Objectives. To explore electroacupuncture's (EA's) effects on fasting blood glucose (FBG) and insulin resistance of type 2 diabetic mellitus (T2DM) model rats and give a possible explanation for the effects. Method. It takes high fat diet and intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) for model preparation. Model rats were randomly divided into T2DM Model group, EA weiwanxiashu (EX-B3) group, and sham EA group (n = 12/group). EA (2 Hz continuous wave, 2 mA, 20 min/day, 6 days/week, 4 weeks) was applied as intervention. FBG, area under curve (AUC) of oral glucose tolerance test (OGTT), insulin resistance index (HOMA-IR), pancreatic B cell function index (HOMA-B), skeletal muscle phosphorylated phosphatidylinositol-3-kinase (PI3K), glucose transporter 4 (GLUT4), and membrane GLUT4 protein expression were measured. Results. EA weiwanxiashu (EX-B3) can greatly upregulate model rat's significantly reduced skeletal muscle PI3K (Y607) and membrane GLUT4 protein expression (P < 0.01), effectively reducing model rats' FBG and AUC of OGTT (P < 0.01). The effects are far superior to sham EA group. Conclusion. EA weiwanxiashu (EX-B3) can upregulate skeletal muscle phosphorylated PI3K protein expression, to stimulate membrane translocation of GLUT4 and thereby increase skeletal muscle glucose intake to treat T2DM. PMID- 27656245 TI - Material flows accounting for Scotland shows the merits of a circular economy and the folly of territorial carbon reporting. AB - BACKGROUND: It is essential that the human race limits the environmental damage created by our consumption. A realistic pathway to limiting consumption would be to transition to a system where materials are conserved and cycled through the economy as many times as possible and as slowly as possible, greatly reducing the greenhouse gas intensive processes of resource extraction, resource processing and waste management. Material flow analysis (MFA) is a method used to understand how materials are consumed within a nation. In this study, we attempt a MFA for Scotland which links carbon emissions to material consumption using data directly based on the mass of materials used in the Scottish economy. It is the first time such an analysis has been conducted for an economy in its entirety. RESEARCH AIMS: This study aims to create a detailed material flow account (MFA) for Scotland, compare the environmental impacts and possible policy implications of different future material consumption scenarios and consider two materials, steel and neodymium, in detail. RESULTS: The model estimated that 11.4 Mg per capita of materials are consumed per year in Scotland, emitting 10.7 Mg CO2e per capita in the process, of which, 6.7 Mg CO2e per capita falls under territorial carbon accounting. Only the circular economy scenario for 2050 allowed for increases in living standards without increases in carbon emissions and material consumption. This result was mirrored in the steel and neodymium case studies-environmental impacts can be minimised by a national strategy that first reduces use, and then locally reuses materials. CONCLUSIONS: Material consumption accounts for a large proportion of the carbon emissions of Scotland. Strategic dematerialisation, particular of materials such as steel, could support future efforts to reduce environmental impact and meet climate change targets. However, policy makers should consider consumption carbon accounting boundaries, as well as territorial boundaries, if carbon savings are to be maximised. This is because imports and recyclate sent abroad can have significant effect on the carbon emissions from material consumption. We demonstrate that the more circular an economy is, the smaller the difference between global and territorial carbon emissions, and therefore that climate change targets based solely on territorial carbon emissions create perverse incentives. The study also found that there could be areas of economic development which are compatible with environmental aims, based around encouraging reprocessing activities in developed nations. PMID- 27656246 TI - Patient empowerment: a mixed blessing? PMID- 27656247 TI - Pregnancy and pulmonary hypertension: a practical approach to management. AB - Pulmonary hypertension remains a major cause of cardiac maternal death in the developed world. Over the last two decades, effective therapies for pulmonary hypertension have been developed, improving symptoms and survival. Consequently, increasing numbers of women with pulmonary hypertension and childbearing potential exist, with a number considering pregnancy. Patients with pulmonary hypertension may also present for the first time during pregnancy or shortly following delivery. The last decade has seen increasing reports of women with pulmonary hypertension surviving pregnancy using a variety of approaches but there is still a significant maternal mortality at between 12% and 33%. Current recommendations counsel that patients with known pulmonary hypertension should be strongly advised to avoid pregnancy with the provision of clear contraceptive advice and termination of pregnancy should be considered in its eventuality. In patients who are fully informed and who have been counselled regarding the risks of continuing with pregnancy, there is growing evidence that a multi-professional approach with expert care in pulmonary hypertension centres may improve outlook, although the mortality remains high. PMID- 27656248 TI - Selective serotonin reuptake inhibitors and pregnancy: A review of maternal, fetal and neonatal risks and benefits. AB - Depression is common in women of childbearing age. Whereas non-pharmacological interventions are recommended as first line interventions, pharmacological treatment may be required. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants in pregnancy. Ideally, discussion of the risks and benefits of SSRI use in pregnancy should occur prior to pregnancy. The potential risks of psychotropic medications need to be balanced against the risks associated with untreated psychiatric conditions and the discontinuation of necessary medications. PMID- 27656250 TI - Completing the cycle: The use of audit to develop a mental health service in times of austerity. AB - BACKGROUND: A published audit demonstrated that a pilot psychiatric clinic failed to capture predicted numbers of women with severe and enduring mental illness. METHODS: On the basis of recommendations from this audit, along with those from the Royal College of Psychiatrists and NICE guidelines, a more comprehensive psychiatric service was developed to meet this demand and therefore manage risk more effectively. RESULTS: Over the course of a year, the new service attracted a higher rate of referrals of pregnant women with severe and enduring mental illness. The majority referral source continued to be midwifery-led. CONCLUSIONS: Audit is a useful tool for evaluating and informing service development and helped us identify further improvements needed to deliver an effective mental health service. PMID- 27656249 TI - Pregnancies complicated by preeclampsia and non-preeclampsia-related nephrotic range proteinuria. AB - OBJECTIVE: To examine the impact of nephrotic range proteinuria during pregnancy on renal, maternal and fetal outcomes. METHODS: A retrospective study of pregnant women with proteinuria greater than 3 g/24 h. Outcome measures included: gestation and mode of delivery, maternal high dependency unit admission, birth weight, maternal blood pressure and proteinuria at time of last follow-up, renal biopsy. RESULTS: Two hundred and sixty four pregnancies in 262 women were reviewed. Postnatal data were available in 180; of these 104 (57%) had urinary protein quantified postnatally. Sixty three (60%) were pure preeclampsia and nine (9%) super-imposed preeclampsia. Biopsy-proven renal disease was newly diagnosed in nine (9%). Sixty three per cent required caesarean section and 34% required high dependency unit admission. There were no maternal deaths. Birth weight corrected for gestation was below the fifth centile in 33%. CONCLUSIONS: The incidence of underlying renal pathology in this cohort is significant and highlights the importance of careful follow-up. PMID- 27656251 TI - Pulmonary hypertension imitating HELLP syndrome. AB - A case of undiagnosed pulmonary hypertension in a woman with mixed connective tissue disease presenting with microangiopathic haemolysis, thrombocytopenia and elevated liver enzymes imitating severe preeclampsia (HELLP syndrome) is described. Connective tissue disorders are associated with an increased prevalence of pulmonary hypertension. Maternal mortality rates with pulmonary hypertension in pregnancy are extremely high. All women with connective tissue disorders should have pulmonary hypertension excluded by echocardiography before attempting conception. End-stage pulmonary hypertension may be associated with haemolysis and thrombocytopenia and thus may imitate severe preeclampsia in pregnant women. There may be a role for extracorporeal membrane oxygenation in the peripartum management of women with severe pulmonary hypertension. PMID- 27656252 TI - A 30-year-old pregnant patient with massive haemoptysis and influenza A: Atypical presentation of a common pathogen. AB - A 30-year-old woman presented at 19 weeks of gestation with symptoms of sore throat, rhinorrhea and haemoptysis that progressed to massive haemoptysis. Her medical history included asthma and a history of smoking prior to pregnancy. Investigations revealed no obvious cause of bleeding. Right lower lobe lobectomy was performed, given the suspicion of a lesion within the intermediate bronchus. The patient developed adult respiratory distress syndrome around 36 h postoperatively. Polymerase chain reaction testing on bronchoalveolar lavage samples was positive for influenza A. Therapy with oseltamivir was initiated. She was discharged two weeks later. This is a rare case of a severe complication from seasonal interpandemic influenza during pregnancy, which underscores the importance of immunization for pregnant women. PMID- 27656253 TI - Pregnancy outcomes in a patient with Sjogren's disease with renal involvement. AB - BACKGROUND: Maternal and fetal outcome in pregnancy with renal failure is unpredictable, where each condition can adversely affect the other. We present a case of steroid sensitive Sjogren's nephritis worsened by pregnancy, demonstrated over the course of multiple pregnancies and investigated the aetiology. CASE: A 28-year-old nullipara with a diagnosis of primary Sjogren's syndrome presented with a deterioration of renal function. A diagnosis of secondary tubulo interstitial nephritis was made on renal biopsy. Her first pregnancy ended in the second trimester with a decision to deliver a female infant at 27 weeks due to worsening maternal renal function. Renal function improved immediately. A second pregnancy ended in a first trimester miscarriage. The third and fourth pregnancies delivered male infants at 35 and 34 weeks, with worsening renal function in each pregnancy, reaching end stage. Repeat biopsy showed extensive glomerulosclerosis and male cells were identified. CONCLUSIONS: This case of Sjogren's syndrome with renal disease demonstrated the increased risk of fetal and maternal adverse pregnancy outcomes. Renal function worsened in each pregnancy and progressed to end-stage renal disease. Fetal microchimerism offers an interesting mechanism for our patient's renal failure and its apparent relationship to her pregnancies. PMID- 27656254 TI - Pulmonary arteriovenous malformation unmasked in pregnancy: A case report. AB - Pulmonary arteriovenous malformations are anomalous communications between arteries and veins of the pulmonary vasculature. Its incidence is rare. Pulmonary arteriovenous malformations can be asymptomatic or cause profound cardiovascular compromise and adverse neurological sequelae, as a result of right to left shunting of deoxygenated blood. Pregnancy and its physiological demands can unmask and exacerbate pulmonary arteriovenous malformations with attendant risks of life threatening complications and rarely, death. This case report describes a first presentation of pulmonary arteriovenous malformation in pregnancy and the tendency for misdiagnosis with pulmonary embolism. A multidisciplinary approach to management is pertinent considering the challenges involved in deciding the appropriate therapeutic management in pregnancy which has to be weighed against potential maternal and fetal risks. PMID- 27656255 TI - A rare case of aggressive squamous cell carcinoma of the bladder in pregnancy. AB - We report a rare case of an aggressive squamous cell carcinoma of the bladder in a young primigravid woman with recurrent urinary tract infections and microscopic haematuria. An emergency caesarean section was performed at 37 weeks gestation for suspected placental abruption; however, she was found to have frank haematuria. Postnatally, an advanced bladder tumour was diagnosed. She required renal dialysis, a radical cystectomy and radiotherapy but sadly died seven months after diagnosis. This case illustrates the importance of thorough investigation of haematuria in pregnancy. Cystoscopy and even tumour resection can be safely performed in pregnancy. Although squamous cell carcinomas account for only 2% of bladder tumours in developed countries, they tend to be large and deeply invasive, requiring radical surgery and chemotherapy or radiotherapy. Management should be multidisciplinary and treatment individualized due to the significant clinical and emotional challenges which arise when a woman develops a malignancy in pregnancy or the puerperium. PMID- 27656256 TI - Pregnancy in women with congenital heart disease. PMID- 27656258 TI - Why Tolerate Conscience? AB - In Why Tolerate Religion?, Brian Leiter argues against the special legal status of religion, claiming that religion should not be the only ground for exemptions to the law and that this form of protection should be, in principle, available for the claims of secular conscience as well. However, in the last chapter of his book, he objects to a universal regime of exemptions for both religious and secular claims of conscience, highlighting the practical and moral flaws associated with it. We believe that Leiter identifies a genuine and important contemporary legal and philosophical problem. We find much to admire in his reasoning. However, we raise questions about two claims that are crucial for his argument. The first claim is that it is not religion as such, but conscience that deserves toleration and respect. The second claim is that respect for religion and conscience demands 'principled toleration' but does not entail stronger policies of legal exemptions. Against the first claim, we argue that Leiter does not successfully distinguish religious belief from secular conscience and morality; and he does not explain why secular conscience (which shares many of religious conscience's epistemic features) deserves respect. Against the second claim, we argue that the most promising theories of legal exemptions are not classical theories of liberal toleration. PMID- 27656257 TI - Development of the Health Literacy Assessment Scale for Adolescents (HAS-A). AB - BACKGROUND: Health literacy has been found to be a crucial component of successful communication and navigation in health care. Various tools have been developed to measure health literacy skills, but few have been developed specifically for adolescents, and most require in-person administration. This study sought to develop a self-report health literacy scale for adolescents to assess four key health literacy domains: the ability to obtain, communicate, understand, and process health information. METHODS: We collected data from 272 youth aged 12-19 recruited from a pediatrics clinic (37%) and the community (63%). We administered the Rapid Estimate of Adolescent Literacy in Medicine Teen, Newest Vital Sign, and three surveys, and used factor analysis to identify scale items. RESULTS: Using multiple health literacy assessments, it was clear that many teens struggle with low health literacy skills. When identifying items that can be used as self-report items in future research, factor analysis identified three subscales; a 5-item communication scale (alpha = 0.77), a 4-item confusion scale (alpha = 0.73), and a 6-item functional health literacy scale (alpha = 0.76). The scales performed reasonably well when compared with validation items. CONCLUSIONS: Self-report items can be used to assess health literacy skills for adolescents when in-person administration is not possible or feasible. Such items will allow for greater study of how health literacy impacts communication in not only health care settings, but for all levels of health communication. The tool will also allow researchers to better understand how adolescent health literacy is related to a variety of health outcomes. Further testing of these scales with different populations is warranted. PMID- 27656259 TI - Calf circumference predicts mobility disability: A secondary analysis of the Mexican health and ageing study. AB - INTRODUCTION: Calf circumference is a surrogate measurement of muscle mass. However, there is scarce evidence on its validity in predicting adverse outcomes such as mobility disability. The aim of this report is to determine if calf circumference could predict incident mobility disability in Mexican 60-year or older adults. METHODS: This is a secondary analysis of the Mexican Health and Aging Study and in particular of its two first waves. Sixty-year or older adults without mobility disability in the first assessment were included and followed-up for two years. Calf circumference quartile groups were compared to test the difference of incident mobility disability. Logistic regression models were fitted to test the independent association when including confounding variables. RESULTS: A total of 745 older adults were assessed, from which 24.4% of the older adults developed mobility disability at follow-up. A calf circumference > 38 cm was associated with a higher risk of developing mobility disability, even after adjustment in the multivariate model, with an odds ratio 0.55 (95% confidence interval 0.31-0.99, P = 0.049). CONCLUSIONS: High calf circumference in Mexican older adults is independently associated with incident mobility disability. This could reflect the impact of adverse health conditions such as obesity (with high fat tissue) or edema. Further research should aim at testing these results in different populations. PMID- 27656260 TI - Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone Induced Oxidative Damage in K562 Cells. AB - Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4 benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure. PMID- 27656262 TI - Apigenin Attenuates Oxidative Injury in ARPE-19 Cells thorough Activation of Nrf2 Pathway. AB - The current study was aimed at evaluating the therapeutic implication of apigenin and to elucidate the underlying mechanism. The tert-butyl hydroperoxide (t-BHP) at 200 MUM was used to induce oxidative stress-associated injury in ARPE-19 cells. Apigenin at concentrations less than 800 MUM did not cause cytotoxic effects on ARPE-19 cells. Cell viability assay showed that apigenin at 200 MUM significantly promoted cell survival in t-BHP-treated ARPE-19 cells. Additionally, apigenin at 100 MUM significantly protected ARPE-19 cells from t BHP-induced apoptosis. Molecular examinations demonstrated that apigenin at 400 MUM significantly upregulated the mRNA and protein expression of Nrf2 and stimulated its nuclear translocation in ARPE-19 cells treated with or without t BHP. Apigenin 400 MUM also significantly elevated the expression of HO-1, NQO1, and GCLM at both mRNA and protein levels in the presence or absence of t-BHP. Furthermore, apigenin at 400 MUM significantly increased the activities of SOD, CAT, GSH-PX, and T-AOC and reduced the levels of ROS and MDA in t-BHP-treated ARPE-19 cells. However, these effects of apigenin were all abolished by being transfected with Nrf2 siRNA. Collectively, our current data indicated that apigenin exerted potent antioxidant properties in ARPE-19 cells challenged with t BHP, which were dependent on activation of Nrf2 signaling. PMID- 27656261 TI - Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation. AB - Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappaB) were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC) or apocynin. Excessive ROS generation and consequent Nrf2 and NF-kappaB translocation were determined after high glucose exposure. NF-kappaB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system. PMID- 27656263 TI - Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation. AB - Oxidative stress plays an essential role in the development of age-related cataract. Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin (Trx), which deteriorates cellular antioxidant system. Our study focused on the autophagy-regulating effect of TBP-2 under oxidative stress in human lens epithelial cells (LECs). Human lens epithelial cells were used for cell culture and treatment. Lentiviral-based transfection system was used for overexpression of TBP-2. Cytotoxicity assay, western blot analysis, GFP/mCherry fused LC3 plasmid, immunofluorescence, and transmission electronic microscopy were performed. The results showed that autophagic response of LECs with increased LC3-II, p62, and GFP/mCherry-LC3 puncta (P < 0.01) was induced by oxidative stress. Overexpression of TBP-2 further strengthens this response and worsens the cell viability (P < 0.01). Knockdown of TBP-2 attenuates the autophagic response and cell viability loss induced by oxidative stress. TBP-2 mainly regulates autophagy in the initiation stage, which is mTOR-independent and probably caused by the dephosphorylation of Akt under oxidative stress. These findings suggest a novel role of TBP-2 in human LECs under oxidative stress. Oxidative stress can cause cell injury and autophagy in LECs, and TBP-2 regulates this response. Hence, this study provides evidence regarding the role of TBP-2 in lens and the possible mechanism of cataract development. PMID- 27656264 TI - Obstructive sleep apnea: Underestimated risk factor in sudden cardiac death in schizophrenia. PMID- 27656265 TI - Applicability of the actigraphy for astronauts in spaceflight. PMID- 27656267 TI - Sexsomnia: A case of sleep masturbation documented by video-polysomnography in a young adult male with sleepwalking. AB - The first case of video-polysomnography (vPSG) documented sleep masturbation in a male is reported, and the second reported case of shift work induced sexsomnia. A 20 y.o. soldier with childhood sleepwalking (SW) developed sleep masturbation and SW triggered by military shift work. vPSG documented two episodes of sleep masturbation from N2 sleep in the fourth sleep cycle and from N3 sleep during the fifth sleep cycle. There was no sleep-disordered breathing nor periodic limb movements. vPSG thus confirmed confusional arousals from NREM sleep as the cause of the masturbation. Bedtime clonazepam therapy controlled the SW but not the masturbation. PMID- 27656266 TI - Substantive nature of sleep in updating the temporal conditions necessary for inducing units of internal sensations. AB - Unlike other organs that operate continuously, such as the heart and kidneys, many of the operations of the nervous system shut down during sleep. The evolutionarily conserved unconscious state of sleep that puts animals at risk from predators indicates that it is an indispensable integral part of systems operation. A reasonable expectation is that any hypothesis for the mechanism of the nervous system functions should be able to provide an explanation for sleep. In this regard, the semblance hypothesis is examined. Postsynaptic membranes are continuously being depolarized by the quantally-released neurotransmitter molecules arriving from their presynaptic terminals. In this context, an incidental lateral activation of the postsynaptic membrane is expected to induce a semblance (cellular hallucination of arrival of activity from its presynaptic terminal, which forms a unit for internal sensation) of the arrival of activity from its presynaptic terminal as a systems property. This restricts induction of semblance to a context of a very high ratio of the duration of the default state of neurotransmitter-induced postsynaptic depolarization to the total duration of incidental lateral activations of the postsynaptic membrane. This requirement spans within a time-bin of a few sleep-wake cycles. Since the duration of quantal release remains maximized, the above requirement can be achieved only by ceiling the total duration of incidental lateral activations of the postsynaptic membrane, which necessitates a state of sleep. PMID- 27656268 TI - Case comparison of sleep features from ear-EEG and scalp-EEG. AB - BACKGROUND: We investigate the potential usability of a novel in-the-ear electroencephalography recording device for sleep staging. METHODS: In one healthy subject we compare simultaneous earelectroencephalography to standard scalp EEG visually and using power spectrograms. Hypnograms independently derived from the records are compared. RESULTS: We find that alpha activity, K complexes, sleep spindles and slow wave sleep can be visually distinguished using earelectroencephalography. Spectral peaks are shared between the two records. Hypnograms are 90.9% similar. CONCLUSION: The results indicate that ear electroencephalography can be used for sleep staging. PMID- 27656269 TI - Sleep complaints and fatigue of airline pilots. AB - This work aimed to determine daytime sleepiness and sleep complaints prevalence and the corresponding influence on perceived fatigue and to evaluate the influence of sociodemographic parameters and labour variables on sleep complaints, sleepiness and fatigue. A questionnaire was developed including socio economic and labour issues and instruments, focused in sleep and fatigue. The response rate was 32% and the final sample had 435 pilots. The prevalence of sleep complaints was 34.9%, daytime sleepiness 59.3% and fatigue 90.6%. The high prevalence of sleep complaints, sleepiness and fatigue was disclosed in pilots, with those who fly short/medium having an added risk of fatigue. PMID- 27656270 TI - Circadian preferences and sleep in 15- to 20-year old Finnish students. AB - PURPOSE: Despite progress in research concerning adolescent and young adult sleep and circadian preferences, several aspects have remained unexamined. This study explored gender and diurnal rhythms in relation to several sleep-related factors: sleep duration, bedtime, wake-up time, tiredness, sleepiness, and optimal subjective sleep duration. METHODS: Circadian preferences and sleep were investigated in 555 (Females N=247) Finnish students aged 15-20. The self-report measures included a shortened version of the Horne-Ostberg Morningness Eveningness Scale, the Epworth Sleepiness Scale as well as items probing feelings of tiredness, optimal subjective sleep durations, and bedtime and wake-up time on the most recent day and a typical weekend. Data were collected from Tuesday to Thursday during an ordinary school week. RESULTS AND CONCLUSION: The most frequent chronotype was the intermediate type (54%), and compared to previous studies, the prevalence of evening-oriented individuals was high (37%), whereas only 9% of the participants were classified as morning oriented. No gender specific or chronotype-specific differences in sleep durations were observed, but girls/women and evening-orientated individuals reported suffering more from sleepiness, compared to boys/men and more morning-typed participants, respectively. About 20% of the total sample indicated that their subjective need for sleep was not satisfied during the weekdays nor the weekend, indicating chronic sleep deprivation. Among girls/women and evening-oriented individuals, the subjective sleep need was greater for weekday nights. PMID- 27656271 TI - Sleep architecture alterations in patients with periodic limb movements disorder during sleep and sleep breathing disorders. AB - INTRODUCTION: Sleep movement disorders includes mainly periodic limb movement and others. The more frequent breathing disorders are: obstructive sleep apnea hypopnea syndrome and primary snoring. OBJECTIVE: To compare sleep architecture in periodic limb movements and breathing disorders of different severity, and weight their interactions. METHODS: We compared sleep architecture in 160 patients, divided in six groups: periodic limb movements (n=25), obstructive apnea only (n=30), periodic limb movements/snoring (n=30), periodic limb movements/mild apnea (n=25), periodic limb movements/moderate apnea (n=25), periodic limb movements/severe apnea (n=26). Polysomnographic variables were compared by analysis of variance and Tukey test. RESULTS: We observed an increase of percentage of awakenings in the group with periodic limb movements/severe apnea. We found an increase of percentage of light sleep in the group with obstructive apnea only with respect to periodic limb movements group. The group with obstructive apnea only presented less rapid eye movements sleep in relation with group with periodic limb movements. We found an increase of awakenings in the group with periodic limb movements/severe apnea to the group with periodic limb movements only. Oxygen saturation showed a decrease in the group with periodic limb movements/severe apnea and obstructive apnea only group to periodic limb movements only group. CONCLUSIONS: Periodic limb movements and breathing disorders, resulted in more additive changes in sleep architecture alterations, than as separately disorders, in a complex interaction. Research in these relations deserve more investigations. PMID- 27656272 TI - Subchronical treatment with Fluoxetine modifies the activity of the MCHergic and hypocretinergic systems. Evidences from peptide CSF concentration and gene expression. AB - In the postero-lateral hypothalamus are located two neuronal systems that utilize the neuropeptides melanin-concentrating hormone (MCH) and hypocretins (also called orexins) as neuromodulators. These systems have reciprocal connections between them, and project throughout the central nervous system. MCH has been involved in the generation of sleep, mainly REM sleep, while hypocretins have a critical role in the generation of wakefulness. MCHergic activity is also involved in the pathophysiology of major depressive disorder (MD). In this regards, intracerebral administration of MCH promotes pro-depressive behaviors (i.e., immobility in the forced swimming test) and REM sleep hypersomnia, which is an important trait of depression. Furthermore, the antagonism of the MCHR-1 receptor has a reliable antidepressant effect, suggesting that MCH is a pro depressive factor. Hypocretins have been also involved in mood regulation; however, their role in depression is still on debate. Taking these data into account, we explored whether systemic subchronical treatment with Fluoxetine (FLX), a serotonergic antidepressant, modifies the concentration of MCH in the cerebrospinal fluid (CSF), as well as the preproMCH mRNA expression. We also evaluated the hypocretinergic system by quantifying the hypocretin-levels in the CSF and the preprohypocretin mRNA expression. Compared to control, FLX increased the levels of preprohypocretin mRNA without affecting the hypocretin-1 CSF levels. On the contrary, FLX significantly decreased the MCH CSF concentration without affecting the preproMCH gene expression. This result is in agreement with the fact that MCH serum level diminishes during the antidepressant treatment in MD, and supports the hypothesis that an increase in the MCHergic activity could have pro-depressive consequences. PMID- 27656274 TI - Prevalence of sleep complaints in Colombia at different altitudes. AB - STUDY OBJECTIVES: To determine the prevalence of sleep complaints in adults in Colombia at different altitudes. DESIGN: Cross-sectional, population-based and observational study. SETTING: Urban areas in three cities (Bogota, Bucaramanga, Santa Marta) located between 15 and 2640 masl. Subjects Over 18 years old. INTERVENTIONS: Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), Berlin questionnaire, STOP-Bang questionnaire and diagnostic criteria for restless leg syndrome (IRLSSG). MEASUREMENTS AND RESULTS: The overall prevalence of sleep complaints was 59.6% (CI 95%: 57.3; 61.8%). According to the Pittsburgh scale, 45.3% (CI 95%: 43.0; 47.5) required medical assistance. The Berlin questionnaire indicated that 19.0% (CI 95%: 17.3; 20.8%) had a high risk of sleep apnea (OSA) compared to 26.9% (CI 95%: 24.9; 29.0%) according to STOP-Bang. Among the subjects, 13.7% (CI 95%: 12.3; 15.3%) had excessive daytime sleepiness and 37.7% (CI 95%: 35.5; 39.8%) had a restless leg syndrome. When comparing cities, significant differences in the overall frequency of subjects requiring care were found between Santa Marta (higher frequency) and the other two cities. Differences in sleep problem frequency (Pittsburgh) were observed between Bogota (higher frequency) and Bucaramanga and also between Santa Marta (higher frequency) and the other two cities. The high risk of OSA (STOP-Bang) was different between Bogota (higher frequency) and Bucaramanga and also between Santa Marta (high frequency) and Bucaramanga. CONCLUSIONS: We observed a high prevalence of sleep complaints with significant differences among the cities, indicating a need to pay a greater attention to these problems. PMID- 27656273 TI - Maternal dietary supplementation with omega-3 polyunsaturated fatty acids confers neuroprotection to the newborn against hypoxia-induced dopamine dysfunction. AB - INTRODUCTION: Up to 84% of prematurely born infants suffer hypoxic, anoxic, and ischemic insults. Those infants with subsequent behavioral, motor or cognitive dysfunction represent 8-11% of all live births. Yet, no interventions employed during pregnancy attenuate risk of morbidity in those at-risk infants. Dietary supplementation with omega-3 polyunsaturated fatty acids (omega-3 PUFAs) has been shown to reduce stroke-induced neuropathology in rat models emulating this adverse clinical event. To extend those studies we sought to determine whether maternal dietary supplementation with omega-3 PUFAs would confer neuroprotection against hypoxia-induced neurochemical dysfunction in newborn rat pups exposed to repetitive hypoxic insults. METHODS: We provided pregnant rats with either a omega-3 PUFA enriched diet or else a standard rat chow diet. At postnatal day 7, pups were assigned randomly to either repetitive hypoxic insults or repetitive bursts of room air. On postnatal day 12, pups were sacrificed and brain dopamine levels characterized. RESULTS: Baseline brain dopamine levels did not differ between rat pups born to dams who received omega-3 PUFA enriched versus standard rat chow diets. Rat pups born to dams maintained on normal diets, who were exposed to five days of repetitive hypoxic insults, experienced a 57% reduction in striatal dopamine levels accompanied by significant apoptosis. In contrast, omega-3 PUFA-enriched newborn pups experienced no loss in striatal dopamine levels, and only minimal apoptosis. CONCLUSIONS: Our findings suggest that it may be feasible to confer neuroprotection against hypoxia-induced dopamine dysfunction to newborns likely to experience hypoxic insults. This could significantly improve the outcomes of those 8-11% of newborns who would otherwise experience hypoxia-induced behavioral, motor and cognitive dysfunction. PMID- 27656276 TI - Napping after complex motor learning enhances juggling performance. AB - The present study examined whether a nap after complex motor learning enhanced the following day's physical performance. Eighteen volunteers met the inclusion criteria and were assigned to either a nap (n=9; men=5; mean age=21.0+/-1.5) or no-nap group (n=9; men=5; mean age=21.9+/-0.3). Participants practiced juggling in the morning and were tested immediately afterwards. Participants of the nap group were given a 70-minute nap opportunity after juggling practice, while the no-nap group stayed awake. Juggling performance was then tested in the evening (retest-1) and the next morning (retest-2). Two-way analysis of variance (group: nap, no-nap*time: test, retest-1, retest-2) found there was a significant effect of test time and a significant group*time interaction. The juggling performance of both groups improved from test to retest-1, respectively. However, the juggling performance level of the nap group was higher than that of the no-nap group at the retest-1. As predicted, a nap promptly after learning motor skills was associated with subsequently improved performance. Moreover, the juggling performance of the nap group showed additional significant improvements in the retest-2. In the no-nap group, however, there were no significant improvements in the juggling performance after nocturnal sleep. These results demonstrate that the benefits of a nap following learning were further enhanced after nocturnal sleep. The present results may provide justification for introducing nap periods into daily athletic training as an active method to improve performance. PMID- 27656275 TI - Risk of obstructive sleep apnea, excessive daytime sleepiness and depressive symptoms in a Nigerian elderly population. AB - OBJECTIVES: To evaluate the risk of obstructive sleep apnea (OSA) in a primary care population of elderly Nigerians and to determine its correlates. METHODS: Clinical and demographic data of 414 elderly individuals in a primary care clinic were obtained. Their risk of OSA was estimated using Berlin questionnaire while Epworth sleepiness scale and the Center for Epidemiologic Studies Depression Scale (CESD-10) were also administered. RESULTS: Of the 414 subjects, 96 (23.2%) met the criteria for a high risk for OSA with a male to female ratio of 1:1. Subjects at high OSA risk (high OSA risk group) were younger than those at low OSA risk (low OSA risk group) (71.4+/-6.8 vs 73.6+/-7.7, p=0.011). Mean body mass index (BMI, kg/m(2)) (27.3+/-5.8 vs 24.7+/-5.1, p<0.001) and waist circumference (WC, cm) (90.7+/-13.1 vs 86.5+/-13.9, p=0.011) were higher in the high OSA risk group compared with the low OSA risk group. A total of 215 (51.9%) and 62 (15.0%) subjects had clinically significant depressive symptoms (CESD-10 score>=10) and excessive daytime sleepiness (EDS), respectively. On regression, the odds of EDS, depressive symptoms, increased BMI and younger age were significantly higher in the high OSA risk group compared with the low OSA risk group. CONCLUSIONS: High risk for OSA and depressive symptoms are common in our sample of elderly Nigerians. Depressive symptoms, EDS, BMI and age independently predict high OSA risk in the elderly. PMID- 27656277 TI - Sleep quality and duration is related with diet and obesity in young adolescent living in Sicily, Southern Italy. AB - The aim of this study was to evaluate the association between sleeping habits, Mediterranean diet pattern, and weight status in an adolescent population. The sample consisted of 1586 individuals aged 11-14 years attending 15 secondary schools of Sicily, Southern Italy. School were randomly selected and the data collected during two school years. Anthropometric data was collected and body composition was assessed by bioelectrical impedance analysis. Demographic information, sleep duration, pediatric daytime sleepiness questionnaire (PDSS), physical activity and dietary habits (including adherence to the Mediterranean Diet using the KIDMED score) were further collected. The mean age was 12+/-0.7 and about 24% were overweight and obese. An inverse correlation between total sleep time and body mass index (beta=-0.829, P=0.021), fat mass (beta=-0.526, P=0.025), and waist circumference (beta=-0.426, P=0.045) was found. Similar results were found for weekdays sleep time, while an inverse relationship was found with PDSS score. Adherence to Mediterranean Diet was higher in under/normal weight adolescent with a significant linear association between the KIDMED score and the PDSS, weekdays sleep time and total sleep time. Sleep duration was also associated positively with fruits and vegetable intake and negatively with sweet and snack consumption and eating outside habits. Short sleep duration and poor sleep were associated with an increase in BMI and fat mass as well as to unhealthy eating behaviors. These findings suggest that sleep patterns could be a potential target for obesity prevention programs in young adolescence. PMID- 27656278 TI - Polysomnographic correlates of inflammatory complement components in young healthy males. AB - A growing body of evidence has delineated the predominant role of humoral mediators of inflammation in linking sleep with immunity. Nonetheless, characterization of the relationship between complement components with inflammatory functions and objective sleep measures has not been performed. In this study we investigated the relationships between objective measures of sleep and complement components with inflammatory functions. Thirty-six healthy male university students (age, 23.94+/-4.23 years; BMI, 23.44+/-2.67 kg/m(2)) completed the study. An RMS Quest 32 polysomnograph (PSG) was used for sleep recording. Non-fasting blood was collected before subjects went to bed on the second night in the sleep laboratory to estimate complement component 3 (C-3), complement component 4 (C-4), complement factor-H (Factor-H), C1-inhibitor (C1INH), complement factor I (CFI) and other inflammatory mediators, such as IL-6 and sICAM-1. Multiple linear regression analysis was used to assess the association between PSG sleep measures and inflammatory mediators. Higher values of C-3 and lower values of sICAM-1, C1INH, and CFI (adjusted model, R2=0.211, p<0.041) predicted longer sleep duration. Lower C-3 (adjusted model, R2=0.078, p<0.055) predicted higher N1 (%). Higher levels of C1INH and CFI and lower values of C-4 (model adjusted R2=0.269, p<0.008) predicted higher N3 (%). Higher C-3, higher C-4, lower IL-6, lower C1INH and lower CFI (model adjusted R2=0.296, p<0.007) predicted higher REM (%). Poor sleep measures were associated with increased levels of pro-inflammatory complement components and decreased anti inflammatory complement components. PMID- 27656279 TI - Resource partitioning between ungulate populations in arid environments. AB - Herbivores are major drivers of ecosystem structure, diversity, and function. Resilient ecosystems therefore require viable herbivore populations in a sustainable balance with environmental resource availability. This balance is becoming harder to achieve, with increasingly threatened species reliant on small protected areas in increasingly harsh and unpredictable environments. Arid environments in North Africa exemplify this situation, featuring a biologically distinct species assemblage exposed to extreme and volatile conditions, including habitat loss and climate change-associated threats. Here, we implement an integrated likelihood approach to relate scimitar-horned oryx (Oryx dammah) and dorcas gazelle (Gazella dorcas) density, via dung distance sampling, to habitat, predator, and geographic correlates in Dghoumes National Park, Tunisia. We show how two threatened sympatric ungulates partition resources on the habitat axis, exhibiting nonuniform responses to the same vegetation gradient. Scimitar-horned oryx were positively associated with plant species richness, selecting for vegetated ephemeral watercourses (wadis) dominated by herbaceous cover. Conversely, dorcas gazelle were negatively associated with vegetation density (herbaceous height, litter cover, and herbaceous cover), selecting instead for rocky plains with sparse vegetation. We suggest that adequate plant species richness should be a prerequisite for areas proposed for future ungulate reintroductions in arid and semi-arid environments. This evidence will inform adaptive management of reintroduced ungulates in protected environments, helping managers and planners design sustainable ecosystems and effective conservation programs. PMID- 27656281 TI - Gangliocytic paraganglioma treated with ampullectomy, A case report. AB - BACKGROUND: Gangliocytic paragangliomas are rare, and typically benign neuroendocrine neoplasms usually found in the second portion of the duodenum. Though recurrence is rare, metastatic cases have been noted. A standardized treatment has not been determined. An endoscopic resection can be carried out, unless metastasis has been noted. We present the case of a patient who underwent an ampullectomy, with successful removal of the tumor, and no recurrence on follow-up. CASE SUMMARY: We present a case involving a 58-year-old gentleman, who presented with dysphagia, and ultimately diagnosed with a periampullary mass proven to be a gangliocytic paraganglioma. The tumor was resected in-toto via an ampullectomy. The patient had no recurrence after twenty-one months. CONCLUSION: In conclusion, we present the case of an incidental gangliocytic paraganglioma occurring in the periampullary region of the patient. Ampullectomy was carried out and to date the patient has had no recurrence. Rarity of this tumor, along with treatment choice, makes it especially worthy of notability. PMID- 27656280 TI - The TNBS-induced colitis animal model: An overview. AB - BACKGROUND: Despite recent advances the pathogenesis of Crohn's disease remains incompletely understood. A variety of animal models have been utilized in an effort to provide further insights and develop more therapeutic options. In order to simulate, to an extent, the pathogenesis and the clinical course of the disease, TNBS induced colitis is often used. Various approaches for inducing TNBS -colitis have been described in the literature. METHODS/RESULTS: In this review, we sought to present the animal model of TNBS induced colitis and outline the pathogenesis, pathophysiology, clinical course and pathological characteristics of the model. Furthermore, we describe the differences among those protocols regarding types of animals and colitis induction. DATA SOURCES: The MEDLINE database was thoroughly searched using the keywords: TNBS, colitis, Crohn's disease, animal model. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Additional articles were gathered and evaluated. CONCLUSION: The aim of this study was to thoroughly present an updated review of the TNBS-induced colitis protocols that are implemented by researchers. PMID- 27656282 TI - Weekly paclitaxel therapy for gastric cancer in patients with renal dysfunction: A case report. AB - A 57-year-old woman was admitted to National Defense Medical College hospital for treatment of gastric cancer with pyloric stenosis. She had been diagnosed with chronic kidney disease (CKD) 10 years prior, but received no hemodialysis. Because of peritoneal dissemination, a palliative distal gastrectomy was performed. In consideration of renal dysfunction, we decided for chemotherapy with paclitaxel, but not S-1 plus cisplatin regimen which is renal toxic agents. On the 29th postoperative day, chemotherapy using paclitaxel was initiated at a dose of 80 mg/m(2). Paclitaxel was administered weekly on days 1, 8, and 15 on a 28-day cycle. The patient tolerated 13 courses of this treatment without any severe adverse effect, such as exacerbation of renal function. Despite the gradual increase in the level of tumor markers, metastases were not detected via radiography during the clinical course. Moreover, renal function was maintained for the duration of the clinical course. To date, standard chemotherapeutic treatment for patients with CKD has not been established. We conclude that weekly paclitaxel is a suitable treatment regimen for patients with renal failure requiring chemotherapy for advanced gastric cancer. PMID- 27656283 TI - Biliary cysts in adults. 26 years experience at a single center. AB - BACKGROUND: Biliary cysts are duct dilatation that can occur on all biliary ducts, 20-25% is diagnosed in adults. The classic triad for the clinical presentation consists on abdominal pain, jaundice and abdominal mass. The standard treatment is surgical resection and bilioenteric anastomosis. The objective of this study is to analyze the prevalence and characteristics of biliary cysts in our center. METHODS: This is an observational retrospective study, we included patients older than 16 years old with biliary cyst from march 1989 to February 2015. The demographic and clinical information was collected from the charts and electronic records available at our Hospital. RESULTS: Biliary cysts were reported on 52 patients, only 25 clinical charts were available. The main symptom was abdominal pain in 21 (84%). The diagnosis was performed with abdominal ultrasound in 16 (64%). The most frequent type was IA in 9 (36%). All patients were treated with surgery as a definitive management. DISCUSSION: Vague clinical presentation results on a delay of the diagnosis and treatment. Surgical resection is recommended for patients since they have an increased risk for malignant transformation. Postoperative complications in our patients were stenosis of bilioenteric anastomosis in 3 (12%) patients. CONCLUSIONS: Biliary cysts require an accurate diagnosis and surgical treatment in order to decrease the risk of malignant transformation and progression of the disease. Precise surgical treatment is needed to achieve complete resection and a long term postoperative follow up is mandatory. PMID- 27656284 TI - A transdisciplinary account of water research. AB - Water research is introduced from the combined perspectives of natural and social science and cases of citizen and stakeholder coproduction of knowledge. Using the overarching notion of transdisciplinarity, we examine how interdisciplinary and participatory water research has taken place and could be developed further. It becomes apparent that water knowledge is produced widely within society, across certified disciplinary experts and noncertified expert stakeholders and citizens. However, understanding and management interventions may remain partial, or even conflicting, as much research across and between traditional disciplines has failed to integrate disciplinary paradigms due to philosophical, methodological, and communication barriers. We argue for more agonistic relationships that challenge both certified and noncertified knowledge productively. These should include examination of how water research itself embeds and is embedded in social context and performs political work. While case studies of the cultural and political economy of water knowledge exist, we need more empirical evidence on how exactly culture, politics, and economics have shaped this knowledge and how and at what junctures this could have turned out differently. We may thus channel the coproductionist critique productively to bring perspectives, alternative knowledges, and implications into water politics where they were not previously considered; in an attempt to counter potential lock-in to particular water policies and technologies that may be inequitable, unsustainable, or unacceptable. While engaging explicitly with politics, transdisciplinary water research should remain attentive to closing down moments in the research process, such as framings, path-dependencies, vested interests, researchers' positionalities, power, and scale. WIREs Water 2016, 3:369-389. doi: 10.1002/wat2.1132 For further resources related to this article, please visit the WIREs website. PMID- 27656285 TI - Does habitat disturbance affect stress, body condition and parasitism in two sympatric lemurs? AB - Understanding how animals react to human-induced changes in their environment is a key question in conservation biology. Owing to their potential correlation with fitness, several physiological parameters are commonly used to assess the effect of habitat disturbance on animals' general health status. Here, we studied how two lemur species, the fat-tailed dwarf lemur (Cheirogaleus medius) and the grey mouse lemur (Microcebus murinus), respond to changing environmental conditions by comparing their stress levels (measured as hair cortisol concentration), parasitism and general body condition across four habitats ordered along a gradient of human disturbance at Kirindy Forest, Western Madagascar. These two species previously revealed contrasting responses to human disturbance; whereas M. murinus is known as a resilient species, C. medius is rarely encountered in highly disturbed habitats. However, neither hair cortisol concentrations nor parasitism patterns (prevalence, parasite species richness and rate of multiple infections) and body condition varied across the gradient of anthropogenic disturbance. Our results indicate that the effect of anthropogenic activities at Kirindy Forest is not reflected in the general health status of both species, which may have developed a range of behavioural adaptations to deal with suboptimal conditions. Nonetheless, a difference in relative density among sites suggests that the carrying capacity of disturbed habitat is lower, and both species respond differently to environmental changes, with C. medius being more negatively affected. Thus, even for behaviourally flexible species, extended habitat deterioration could hamper long-term viability of populations. PMID- 27656286 TI - Molecular characterization of Salmonella enterica serotype Enteritidis isolates from food and human samples by serotyping, antimicrobial resistance, plasmid profiling, (GTG)5-PCR and ERIC-PCR. AB - In recent years, Salmonella enterica serovar Enteritidis has been a primary cause of human salmonellosis in many countries. The major objective of this study was to investigate genetic diversity among Salmonella Enteritidis strains from different origins (food and human) by Enterobacterial Repetitive Intergenic Consensus (ERIC) -PCR, as well as to assess their plasmid profiling and antimicrobial resistance. A total of 30 Salmonella Enteritidis isolates, 15 from food samples (chicken, lamb, beef and duck meats) and 15 from clinical samples were collected in Tehran. Identification of isolates as Salmonella was confirmed by using conventional standard biochemical and serological tests. Multiplex-PCR was used for serotyping of isolates to identify Salmonella Enteritidis. Antimicrobial susceptibility testing to 16 agents founds drug resistance patterns among Salmonella Enteritidis isolates. No resistance was observed to cephalexin, ceftriaxone, ceftazidime and cefotaxime, ciprofloxacin, imipenem or meropenem, chloramphenicol and gentamicin. The highest resistance (96.7%) was observed to nitrofurantoin. Seven plasmid profiles (P1-P7) were detected, and a 68-kb plasmid was found in all isolates. Two different primers; ERIC and (GTG)5 were used for genotyping, which each produced four profiles. The majority of clinical and food isolates fell into two separate common types (CTs) with a similar percentage of 95% by ERIC-PCR. Using primer (GTG)5, 29 isolates incorporated in three CTs with 70% of isolates showing a single banding pattern. Limited genetic diversity among human and food isolates of Salmonella Enteritidis may indicate that contaminated foods were possibly the source of human salmonellosis. These results confirmed that ERIC-PCR genotyping has limited discriminatory power for Salmonella Enteritidis of different origin. PMID- 27656287 TI - A 12p13 GRIN2B deletion is associated with developmental delay and macrocephaly. AB - N-methyl D-aspartate receptor subtype 2B (GluN2B), encoded by GRIN2B, is one of the components of the N-methyl D-aspartate receptor protein. Aberrations in GRIN2B have been reported to be responsible for various types of neurodevelopmental disorders. We report a Japanese boy with an ~2 Mb interstitial deletion in 12p13 involving the entire GRIN2B gene, who presented with intellectual disability, motor developmental delay and marked macrocephaly. PMID- 27656288 TI - A novel missense mutation of COL5A2 in a patient with Ehlers-Danlos syndrome. AB - Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg]. PMID- 27656289 TI - The Epidemiology of Leptospira Infection in Mazandaran Province, Northern Iran, During 2012 - 2013. PMID- 27656290 TI - The Lived Experience of Psoriasis Patients from Social Stigma and Rejection: A Qualitative Study. AB - BACKGROUND: Psoriasis is a common, chronic skin disease that causes challenges such as stigma and labeling from both the community and individuals due to its effects on appearance. OBJECTIVES: The objective of this study was to describe and explain the social stigma and rejection experienced by patients with psoriasis. PATIENTS AND METHODS: The present research is a qualitative study with a hermeneutic phenomenological approach conducted among psoriasis patients referring to the dermatology clinic and ward of Imam Khomeini hospital in Ahvaz, Iran between June and December 2014. In this study, 15 patients with psoriasis were selected by purposeful sampling, and they were asked to express their experience of stigma and rejection. The data were collected through in-depth semi structured interviews, and Diekelmann and colleagues' method was used for data analysis. RESULTS: After analysis of interviews, four themes were extracted: lack of social support, unrealistic and inappropriate labeling, rejection and isolation, and feeling of absurdity and futility. These can be indicative of the patients' experience from social stigma and rejection phenomena. CONCLUSIONS: Patients' experiences of stigma and rejection phenomena indicated that all aspects of their lives are affected. Moreover, these findings highlight the significance of stigma and rejection concepts in providing better care to these patients. PMID- 27656291 TI - Split Rib Cranioplasty for Frontal Osteoma: A Case Report and Review of the Literature. AB - INTRODUCTION: Osteomas are benign bone tumors. They generally lead to a local thickness on the frontal bone in calvarium. When they occur on the forehead, they often cause a cosmetic disorder without any neurological symptoms. The significant problem is the repair method of the cranium defect. CASE PRESENTATION: The rib of a 34-year-old female was split and used for a small cranium defect of 3 * 3.5 cm. The preferred method and the obtained results were presented under the guidance of the literature. CONCLUSIONS: Along with the technological advancement, different materials are employed according to the size of the cranium defect and the age of the case. The application of split costa cranioplasty for the small cranium defects in the region of patient's face is the method with the least possibility of complications, and its cosmetic and functional results are quite promising. PMID- 27656293 TI - Predictors of Treatment Outcome for Retreatment Pulmonary Tuberculosis Cases among Tribal People of an Eastern India District: A Prospective Cohort Study. AB - Objective. The study was conducted to assess the treatment outcome of different category retreatment cases with the aim of finding out the important predictors of unfavorable outcomes. Methodology. This hospital based prospective cohort study was conducted in three tuberculosis units (TUs) of west Midnapore (a district of Eastern India), covering mostly the tribal populated areas. Patients who were registered for Category II antituberculosis treatment between 1st quarter of 2013 (Jan to Mar) and 4th quarter of 2013 (Oct to Dec) were considered as our study cohort and they were followed up till December 2014. The study was started with 177 patients but ultimately ended with 165 patients. Results. Unfavorable outcome was observed among 24.8% patients. Among them mostly 51.2% were defaulter, 22% were failure case, and 26.8% died during treatment. Patients, who were minority by religion, were found 4 times more vulnerable for unfavorable outcome. Unfavorable outcome was found 7 times more common among retreatment TB cases who remain sputum positive after completion of initiation phase of Category II treatment. Conclusion. Programmatic approach should be specified to address the minority by religion population and to reduce the load of sputum positive cases after completion of initiation phase treatment by tracking them. PMID- 27656292 TI - Effect of Hydroxychloroquine on the Retinal Layers: A Quantitative Evaluation with Spectral-Domain Optical Coherence Tomography. AB - Purpose. To evaluate the effect of hydroxychloroquine on retinal pigment epithelium- (RPE-) Bruch's membrane complex, photoreceptor outer segment, and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses using spectral domain optical coherence tomography (SD-OCT). Methods. In this prospective case control study, 51 eyes of 51 hydroxychloroquine patients and 30 eyes of 30 healthy subjects were included. High-quality images were obtained using a Cirrus HD-OCT with 5-line raster mode; the photoreceptor inner segment (IS) and outer segment (OS), sum of the segments (IS + OS), and RPE-Bruch's membrane complex were analyzed. Results. The thicknesses of the IS + OS and OS layers were significantly lower in the hydroxychloroquine subjects compared to the control subjects (P < 0.05). RPE-Bruch's membrane complex thicknesses were significantly higher in the hydroxychloroquine subjects than for those of the control subjects (P < 0.05). The minimum and temporal-inferior macular GCIPL thicknesses were significantly different between the patients with hydroxychloroquine use and the control subjects (P = 0.04 and P = 0.03, resp.). Conclusions. The foveal photoreceptor OS thinning, loss of GCIPL, and RPE-Bruch's membrane thickening were detected in patients with hydroxychloroquine therapy. This quantitative approach using SD-OCT images may have important implications to use as an early indicator of retinal toxicity without any visible signs of hydroxychloroquine retinopathy. PMID- 27656294 TI - Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis. AB - Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7%) of early response, 122 (18.9%) of delayed response, and 144 (22.3%) of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (p value < 0.001 for all comparisons). Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter. PMID- 27656295 TI - Perspectives on the Role and Synergies of Architecture and Social and Built Environment in Enabling Active Healthy Aging. AB - Research has demonstrated that enabling societal and physical infrastructure and personal accommodations enhance healthy and active aging throughout the lifespan. Yet, there is a paucity of research on how to bring together the various disciplines involved in a multidomain synergistic collaboration to create new living environments for aging. This paper aims to explore the key domains of skills and knowledge that need to be considered for a conceptual prototype of an enabling educational process and environments where healthcare professionals, architects, planners, and entrepreneurs may establish a shared theoretical and experiential knowledge base, vocabulary, and implementation strategies, for the creation of the next generation of living communities of active healthy adults, for persons with disabilities and chronic disease conditions. We focus on synergistic, paradigmatic, simple, and practical issues that can be easily upscaled through market mechanisms. This practical and physically concrete approach may also become linked with more elaborate neuroscientific and technologically sophisticated interventions. We examine the domains of knowledge to be included in establishing a learning model that focuses on the still understudied impact of the benefits toward active and healthy aging, where architects, urban planners, clinicians, and healthcare facility managers are educated toward a synergistic approach at the operational level. PMID- 27656296 TI - Crystal Structures of Two Isozymes of Citrate Synthase from Sulfolobus tokodaii Strain 7. AB - Thermoacidophilic archaeon Sulfolobus tokodaii strain 7 has two citrate synthase genes (ST1805-CS and ST0587-CS) in the genome with 45% sequence identity. Because they exhibit similar optimal temperatures of catalytic activity and thermal inactivation profiles, we performed structural comparisons between these isozymes to elucidate adaptation mechanisms to high temperatures in thermophilic CSs. The crystal structures of ST1805-CS and ST0587-CS were determined at 2.0 A and 2.7 A resolutions, respectively. Structural comparison reveals that both of them are dimeric enzymes composed of two identical subunits, and these dimeric structures are quite similar to those of citrate synthases from archaea and eubacteria. ST0587-CS has, however, 55 ion pairs within whole dimer structure, while having only 36 in ST1805-CS. Although the number and distributions of ion pairs are distinct from each other, intersubunit ion pairs between two domains of each isozyme are identical especially in interterminal region. Because the location and number of ion pairs are in a trend with other CSs from thermophilic microorganisms, the factors responsible for thermal adaptation of ST-CS isozymes are characterized by ion pairs in interterminal region. PMID- 27656297 TI - Mandibular Fractures Admitted to the Emergency Department: Data Analysis from a Swiss Level One Trauma Centre. AB - Mandibular fracture is a common occurrence in emergency medicine and belongs to the most frequent facial fractures. Historically road traffic injuries (RTIs) have played a prominent role as a cause for mandibular fractures. We extracted data from all patients between August 2012 and February 2015 with "lower jaw fracture" or "mandibular fracture" from the routine database from the emergency department. We conducted a descriptive analysis at a Swiss level one trauma centre. 144 patients were admitted with suspected mandibular fractures. The majority underwent CT diagnostic (83%). In 7% suspected mandibular fracture was not confirmed. More than half of all patients suffered two or more fractures. The fractures were median or paramedian in 77/144 patients (53%) and in other parts (corpus, mandibular angle, ramus mandibularis, collum, and temporomandibular joint) in 100/144 (69%). Male to female ratio was 3 : 1 up to 59 years of age; 69% were younger than 40 years. 72% of all patients presented during daytime, 69% had to be hospitalized, and 31% could be discharged from the ED after treatment. Most fractures were due to fall (44%), followed by interpersonal violence (25%) and sport activities (12%). Falls were a dominant cause of fracture in all age groups while violence and sport activities were common only in younger patients. Comparisons to other studies were difficult due to lack of standardization of causes contributing to the injuries. In the observed time period and setting RTIs have played a minor role compared to falls, interpersonal violence, and sports. In the future, standardized documentation as well as categorization of causes for analytic purposes is urgently needed to facilitate international comparison of studies. PMID- 27656298 TI - Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons. AB - The aim of this study was to determine the causative agent of acute respiratory infection (ARI) in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV) (28.6%), followed by parainfluenza viruses (PIVs) types 1-3 (18.4%), rhinovirus (HRV) (14.3%), human metapneumovirus (10.1%), adenovirus (AdV) (7.1%), influenza viruses types A and B (4.8%), and coronaviruses (4.2%). In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%), bocavirus (HBoV) (10.5%), PIV-4 (2.6%), and parechovirus (1.3%). There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease (P > 0.05). AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses (P < 0.001). PMID- 27656299 TI - The Role of TEE in Diagnosing Hepatopulmonary Syndrome and Cryptogenic Cirrhosis. AB - In the vast majority of cases, ongoing hypoxemia in a cirrhotic patient is usually hepatopulmonary syndrome (HPS) until proven otherwise; in this case, HPS was suspected prior to any known diagnosis of cirrhosis. This is the first reported case in the literature whereby HPS and cirrhosis were diagnosed after the fact, rather than with the preexisting knowledge of liver cirrhosis. PMID- 27656300 TI - Pneumothorax Causing Pneumoperitoneum: Role of Surgical Intervention. AB - The most common cause of a pneumoperitoneum is a perforation of a hollow viscus and the treatment is an exploratory laparotomy; nevertheless, not all pneumoperitoneums are due to a perforation and not all of them need surgical intervention. We hereby present a case of pneumoperitoneum due to a diaphragmatic defect, which allowed air from a pneumothorax to escape through the diaphragmatic hernia into the abdominal cavity. PMID- 27656301 TI - Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus. AB - Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH. PMID- 27656302 TI - Q Fever Risk in Patients Treated with Chronic Antitumor Necrosis Factor-Alpha Therapy. AB - Q fever is a zoonotic bacterial disease caused by Coxiella burnetii. Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the defense against infection with this Gram-negative coccobacillus. Theoretically, patients who are treated with anti-TNF-alpha medications are at risk for developing chronic Q fever. We present two patients who developed Q fever while being treated with anti-TNF-alpha agents and discuss the significance of timely diagnosis of C. burnetii infection in these patients. PMID- 27656303 TI - Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature. AB - Introduction. Papillary squamotransitional cell carcinoma (PSTCC) is an uncommon histopathological variant of squamous cell carcinoma (SCC) of the uterine cervix, which occurs in postmenopausal women. Presentation of Case. Herein, we describe a case of a 63-year-old woman who presented with 4-month history of postmenopausal vaginal bleeding. Vaginal examination revealed a fragile lesion of size 1 * 1 cm invading left posterior vaginal fornice and parametrium. Biopsy showed the presence of papillae containing fibrovascular cores lined by multilayered atypical epithelial cells resembling squamous and transitional cell epithelium, confirming the diagnosis of PSTCC of the uterine cervix. After staging work-up she was staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system 2009 as FIGO IIB, and she was started on extended field concurrent chemoradiation. Discussion. PSTCC of the uterine cervix is an extremely rare and aggressive entity. PSTCC is often characterized by the presence of papillary structures with prominent fibrovascular cores. PSTCC of the uterine cervix should be differentiated from transitional cell carcinoma, squamous papilloma, papillary adenocarcinoma, and cervical intraepithelial neoplasia with papillary features. Conclusion. PSTCC of the uterine cervix is a diagnostic challenge; further studies regarding the mechanism underlying the development of PSCC are warranted. PMID- 27656304 TI - Unusual Closed Traumatic Avulsion of Both Flexor Tendons in Zones 1 and 3 of the Little Finger. AB - Closed tendon avulsion of both flexor tendons in the same finger is an extremely rare condition. We encountered the case of a patient who presented a rupture of the flexor digitorum profundus in zone 1 and flexor digitorum superficialis in zone 3 in the little finger. This occurrence has not been reported previously. We hereby present our case, make a review of the literature of avulsion of both flexor tendons of the same finger, and propose a treatment according to the site of the ruptures. PMID- 27656305 TI - Symptomatic Bilateral Torn Discoid Medial Meniscus Treated with Saucerization and Suture. AB - Discoid meniscus is an anatomical congenital anomaly more often found in the lateral meniscus. A discoid medial meniscus is a very rare anomaly, and even more rare is to diagnose a bilateral discoid medial meniscus although the real prevalence of this situation is unknown because not all the discoid medial menisci are symptomatic and if the contralateral knee is not symptomatic then it is not usually studied. The standard treatment of this kind of pathology is partial meniscectomy. Currently the tendency is to be very conservative so suture and saucerization of a torn discoid meniscus when possible are gaining support. We present the case of a 13-year-old patient who was diagnosed with symptomatic torn bilateral discoid medial meniscus treated by suturing the tear and saucerization. To the best of our knowledge this is the first case reported of bilateral torn discoid medial meniscus treated in this manner in the same patient. PMID- 27656306 TI - Tympanosclerosis Presenting as Mass: Workup and Differential. AB - Introduction. Tympanosclerosis is a commonly encountered entity within ENT clinics and primary care settings. Recognizing ear pathology is essential for correct management. Oftentimes the diagnosis is clear; however in certain cases further workup to rule out other more insidious disease processes is warranted. Case Report. We present a case of tympanosclerosis which presented as an ear mass without classic appearance of tympanosclerosis. Through imaging and biopsy the diagnosis of tympanosclerosis was made. The patient was treated surgically with good outcome. Discussion. Various ear pathologies, with different treatment algorithms, may present as clinically similar to one another. Differential diagnosis for this case included tympanosclerosis, cholesteatoma, or other middle ear masses. We review these entities and discuss their pathophysiology and implications on management. PMID- 27656307 TI - Cystic and Papillary Neoplasm at the Hepatic Hilum Possibly Originating in the Peribiliary Glands. AB - Cystic neoplasms of the liver are divided into two types: mucinous cystic neoplasm and cystic intraductal papillary neoplasm of the bile duct. We herein report two cases of cystic and papillary neoplasm of the liver which differed from the abovementioned types. Case 1. A 70-year-old man. Radiologically, a cystic tumor measuring 20 mm in diameter was found at the hepatic hilum. Right hepatectomy was performed under a diagnosis of intrahepatic cholangiocarcinoma (iCCA) based on the imaging findings. Case 2. A 70-year-old man. Radiologically, a cystic tumor measuring 60 mm in diameter was found at the hepatic hilum. Under a diagnosis of iCCA, left hepatic trisectionectomy was performed. In both cases, endoscopic retrograde cholangiography did not demonstrate communication between the cystic tumor and adjacent bile ducts. Pathologically, these two tumors were cystic neoplasms located at the hepatic hilum and were morphologically characterized by an intracystic papillary neoplasm composed of diffuse high-grade dysplasia and associated with an invasive carcinoma. Ovarian-like stroma was not found in the capsule of these tumors. Interestingly, there were peribiliary glands near these tumors, and MUC6 was expressed in these papillary neoplasms as well as in the peribiliary glands. These neoplasms might have arisen from the peribiliary glands. PMID- 27656308 TI - Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells. AB - The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID- 27656309 TI - Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis. AB - We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting. PMID- 27656310 TI - The Challenges and Relevance of Exploring the Genetics of North Africa's "Barbary Lion" and the Conservation of Putative Descendants in Captivity. AB - The lions of North Africa were unique in ecological terms as well as from a human cultural perspective and were the definitive lions of Roman and Medieval Europe. Labelled "Barbary" lions, they were once numerous in North Africa but were exterminated by the mid-20th century. Despite subsequent degeneration of the Atlas Mountain ecosystem through human pressures, the feasibility of lion reintroduction has been debated since the 1970s. Research on the long-established captive lion collection traditionally kept by the sultans and kings of Morocco has enabled selective breeding coordinated across Moroccan and European zoos involving a significant number of animals. Molecular genetic research has recently provided insights into lion phylogeny which, despite previous suggestions that all lions share recent common ancestry, now indicates clear distinctions between lions in North, West, and Central Africa, the Middle East, and India versus those in Southern and Eastern Africa. A review of the evolutionary relevance of North African lions highlights the important challenges and opportunities in understanding relationships between Moroccan lions, extinct North African lions, and extant lion populations in India and West and Central Africa and the potential role for lions in ecosystem recovery in those regions. PMID- 27656311 TI - Parkinson's Disease and Homocysteine: A Community-Based Study in a Folate and Vitamin B12 Deficient Population. AB - Background. Homocysteine (Hcy) levels were higher in patients with Parkinson's disease (PD). This could be partially explained by levodopa treatment. Whether untreated PD patients have higher Hcy levels is contradictory. Methods. A community-based study was conducted using a two-stage approach for subjects >= 55 years to find PD patients in 3 towns of Luliang City. Blood samples were collected. Serum Hcy, folate, and vitamin B12 concentrations were measured. For each untreated PD patient, 5 controls were selected matched with age and sex to evaluate the relationship between Hcy levels and PD. Results. Of 6338 eligible residents, 72.7% participated in the study. 31 PD cases were identified. The crude prevalence of PD for people >= 55 years was 0.67%. Blood samples were collected from 1845 subjects, including 17 untreated PD patients. There was no difference for concentrations of serum Hcy, folate, and vitamin B12 between cases and controls (P > 0.05). In univariate and multivariate analysis, there was significant inverse relation between PD and current smoking (P < 0.05). No other factor was significant statistically. Conclusions. The prevalence of PD was comparable to earlier studies in China. Hyperhomocysteinemia was not a risk factor of PD, as well as folate and vitamin B12 deficiency. PMID- 27656312 TI - Investigation of Anaplasma marginale Seroprevalence in a Traditionally Managed Large California Beef Herd. AB - Recent observations by stakeholders suggested that ecosystem changes may be driving an increased incidence of bovine erythrocytic anaplasmosis, resulting in a reemerging cattle disease in California. The objective of this prospective cohort study was to estimate the incidence of Anaplasma marginale infection using seroconversion in a northern California beef cattle herd. A total of 143 Black Angus cattle (106 prebreeding heifers and 37 cows) were enrolled in the study. Serum samples were collected to determine Anaplasma marginale seroprevalence using a commercially available competitive enzyme-linked immunosorbent assay test kit. Repeat sampling was performed in seronegative animals to determine the incidence density rate from March through September (2013). Seroprevalence of heifers was significantly lower than that of cows at the beginning of the study (P < 0.001) but not at study completion (P = 0.075). Incidence density rate of Anaplasma marginale infection was 8.17 (95% confidence interval: 6.04, 10.81) cases per 1000 cow-days during the study period. Study cattle became Anaplasma marginale seropositive and likely carriers protected from severe clinical disease that might have occurred had they been first infected as mature adults. No evidence was found within this herd to suggest increased risk for clinical bovine erythrocytic anaplasmosis. PMID- 27656313 TI - Image guidance in skull base tumor resection: A synergistic approach using intraoperative navigated angiosonography for real-time vessel visualization. PMID- 27656315 TI - Do corticosteroids play a role in the management of traumatic brain injury? AB - Neuroprotective strategies for the medical management of traumatic brain injury (TBI) have been elusive. While laboratory studies provide a conceptual framework for the potential efficacy of corticosteroids in this context, clinical trials testing this hypothesis have yielded no convincing evidence of clinical benefit. Here, we review the five key randomized control trials (RCTs) that have examined this issue. Based on the proposed primary endpoints of these RCTs, the five RCTs consistently showed that corticosteroids do not confer significant benefit in the TBI population. PMID- 27656316 TI - Erratum: Treatment options for pediatric craniopharyngioma. AB - [This corrects the article on p. S174 in vol. 7, PMID: 27057397.]. PMID- 27656317 TI - Multifocal melanocytoma of the posterior fossa and subcutaneous scalp in the absence of neurocutaneous melanosis. AB - BACKGROUND: Primary leptomeningeal melanocytic neoplasms of the central nervous system are rare. Multifocal lesions typically occur in the setting of cutaneous melanosis. We present the first report of a posterior fossa melanocytoma and subcutaneous melanocytoma of intermediate grade in the absence of cutaneous melanosis. CASE DESCRIPTION: We present the case of a 22-year-old male with decreased hearing on the right side, ataxia, nausea, vomiting and a scalp mass. Magnetic resonance imaging (MRI) demonstrated occipital and cerebellopontine (CP) angle masses. The patient underwent gross total resection of the scalp mass and subtotal resection of the CP angle mass. Pathologic examination revealed melanocytoma with intermediate grade. The patient underwent stereotactic radiosurgery to the residual CP angle tumor. This case represents, to the author's knowledge, the first report associating a posterior fossa melanocytoma with a subcutaneous melanocytoma of intermediate grade in the absence of cutaneous melanosis. CONCLUSION: This case introduces the first report of a new variant of multifocal melanocytoma which is not confined to the central nervous system. PMID- 27656318 TI - Suprasellar epithelioid hemangioendothelioma: Case report and review of the literature. AB - BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare sarcoma of vascular origin, which is clinically and histologically intermediate between benign hemangioma and angiosarcoma. It is most commonly found in the liver, lung, and bone, however, 46 intracranial cases have been reported in the literature, of which this is the fifth reported suprasellar tumor. CASE DESCRIPTION: A 45-year old woman developed progressive lethargy, somnolence, and memory decline over the course of 6 months. On computed tomography (CT), she was found to have a large hypothalamic mass and underwent subtotal resection via a bifrontal craniotomy. CONCLUSIONS: While primary intracranial EHE is an uncommon presentation of a rare tumor, the suprasellar region does not seem to be an unusual location when it does occur. Prognosis is generally good, and may be better for primary intracranial disease than that for EHE originating elsewhere. Surgery is the first line of therapy, with variable benefit from adjuvant chemotherapy or radiation when total resection is not possible. Chemotherapeutic approaches in current use are directed at preventing endothelial proliferation. PMID- 27656319 TI - Brain metastases from breast cancer during pregnancy. AB - BACKGROUND: Brain metastasis during pregnancy is a rare occurrence. In particular, there have only been three prior cases regarding breast cancer metastasis. We report a patient with breast cancer metastasis to the brain during pregnancy and review the literature. CASE DESCRIPTION: The patient was a 35-year old female with a history of breast cancer (estrogen receptor/progesterone receptor negative, human epidermal growth factor receptor 2/neu positive, status post-neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab therapy, status post-bilateral mastectomies), and prior right frontal brain metastases (status post-resection, capecitabine/lapatinib/temozolomide therapy, and cyberknife treatment). Patient was found to be pregnant at 9 weeks' gestation while on chemotherapy; the patient elected to continue with the pregnancy and chemotherapy was discontinued. At 14 weeks' gestation, she returned with recurrent right frontal disease. She was taken for a craniotomy at 16 weeks' gestation, which confirmed metastases. Six weeks later, patient returned with worsening headaches and fatigue, with more recurrent right frontal disease. She was started on decadron and chemotherapy (5-fluorouracil, adriamycin, and cyclophosphamide). Serial magnetic resonance imaging (MRI) demonstrated enlarging right frontal lesions. She underwent a craniotomy at 27 weeks' gestation, and chemotherapy was discontinued promptly. Starting at 30 weeks' gestation, she received whole brain radiation for 2 weeks. Subsequently, she delivered a baby girl via cesarean section at 32 weeks' gestation. At 6 weeks follow-up, an MRI brain demonstrated no new intracranial disease, with stable postoperative findings. CONCLUSION: There is a lack of guidelines and clinical consensus on medical and surgical treatment for breast cancer metastases in pregnant patients. Treatment usually varies based upon underlying tumor burden, location, gestational age of the fetus, and patient's preference and symptomatology. PMID- 27656314 TI - Metabolic syndrome and the hepatorenal reflex. AB - Insufficient hepatic O2 in animal and human studies has been shown to elicit a hepatorenal reflex in response to increased hepatic adenosine, resulting in stimulation of renal as well as muscle sympathetic nerve activity and activating the renin angiotensin system. Low hepatic ATP, hyperuricemia, and hepatic lipid accumulation reported in metabolic syndrome (MetS) patients may reflect insufficient hepatic O2 delivery, potentially accounting for the sympathetic overdrive associated with MetS. This theoretical concept is supported by experimental results in animals fed a high fructose diet to induce MetS. Hepatic fructose metabolism rapidly consumes ATP resulting in increased adenosine production and hyperuricemia as well as elevated renin release and sympathetic activity. This review makes the case for the hepatorenal reflex causing sympathetic overdrive and metabolic syndrome in response to exaggerated splanchnic oxygen consumption from excessive eating. This is strongly reinforced by the fact that MetS is cured in a matter of days in a significant percentage of patients by diet, bariatric surgery, or endoluminal sleeve, all of which would decrease splanchnic oxygen demand by limiting nutrient contact with the mucosa and reducing the nutrient load due to the loss of appetite or dietary restriction. PMID- 27656320 TI - Ollier disease with anaplastic astrocytoma: A review of the literature and a unique case. AB - BACKGROUND: Ollier disease is a rare, nonfamilial disorder that primary affects the long bones and cartilage of joints with multiple enchondromas. It is associated with a higher risk of central nervous system (CNS) malignancies; although the incidence is unknown. CASE DESCRIPTION: Here, we present the case of a 55-year-old woman who developed an anaplastic astrocytoma with a known diagnosis of Ollier disease with a survival time of over 3 years. CONCLUSION: This report draws attention to the rarity of this disease and the paucity of information regarding CNS involvement in Ollier disease, as well as reviews the current literature. PMID- 27656321 TI - Lymphomatoid granulomatosis of the brain: A case report. AB - BACKGROUND: Lymphomatoid granulomatosis is a rare disorder of the central nervous system (CNS) with few cases being reported in literature. We present the case of an adult with an unusual lesion of the CNS who presented with motor seizures and was diagnosed with lymphomatoid granulomatosis, followed by a discussion of the process of evaluation and management. CASE DESCRIPTION: A 42-year-old male presented with motor seizures and loss of consciousness for 10 minutes along with dysarthria and left hemiplegia. Neurological examination and imaging with magnetic resonance imaging (MRI) of the brain revealed a mass in the right striatum. The patient was hospitalized and underwent an image-guided right frontal craniotomy using the Leksell Stereotactic G-Frame. Pathology reported a lymphomatoid granulomatosis. Being immunocompetent, the patient received medical treatment with prednisone and rituximab. Two years after his diagnosis, the patient had no active disease and his brain MRI did not show contrast enhancement. After almost 3 years of follow-up, the patient has a mild weakness in the left-side of his body (4/5), is seizure-free, and can walk and perform daily activities. CONCLUSIONS: This rare lesion in an adult, immunocompetent patient, debuting with motor seizures represents a challenge in terms of diagnosis and treatment. After surgical and medical treatment, the patient had a satisfactory recovery. Clinical features, imaging, differential diagnosis, and pathology are discussed. PMID- 27656323 TI - HEAVEN: The Frankenstein effect. AB - The HEAVEN head transplant initiative needs human data concerning the acute restoration of motor transmission after application of fusogens to the severed cord in man. Data from two centuries ago prove that a fresh cadaver, after hanging or decapitation, can be mobilized by electrical stimulation for up to 3 hours. By administering spinal cord stimulation by applied paddles to the cord or transcranial magnetic stimulation to M1 and recording motor evoked potentials, it should be possible to test fusogens in fresh cadavers. Delayed neuronal death might be the neuropathological reason. PMID- 27656322 TI - Management and outcomes of intramedullary spinal cord tumors: A single center experience from a developing country. AB - BACKGROUND: Intraoperative neurophysiology, high magnification microscopes, and ultrasonic aspirators are considered essential aid for the safe resection of intramedullary spinal cord tumors (IMSCTs). Most centers in developing countries such as Pakistan still lack these facilities. The purpose of this study was to review the management of IMSCTs at our hospital and to determine factors associated with the outcomes of surgery. METHODS: This was a retrospective review of medical records of adult patients undergoing surgery for IMSCT over 12 years. The institutional ethical review committee approved this study. Data were collected regarding demographics, clinical and radiological features, and surgical details. Modified McCormick Scale was used to grade patients' neurological status at admission, discharge, and follow-up. Statistical analysis was performed using the Statistical Package for Social Sciences version 22. RESULTS: Forty three cases were reviewed. Mean age was 33.8 +/- 15.1 years whereas median follow-up was 5 months (range: 0.25-96 months). Most patients had ependymoma (n = 16; 73%). Cervical region was the most commonly involved (n = 15; 34.9%). Gross total resection (GTR) was achieved in 30 cases (69.8%). The preoperative McCormick grade was significantly associated with follow-up McCormick grade (P value = 0.002). Eight patients (18.6%) underwent intraoperative electrophysiological monitoring, out of which GTR was achieved in all cases, and none had disease progression or recurrence. Ten patients received postoperative radiotherapy. Thirty five patients (81.4%) had progression free survival at last follow-up. CONCLUSIONS: We achieved a GTR rate of 68.9% for IMSCTs with limited resources. In few cases, where intraoperative electrophysiology was used, the rate of GTR was 100%. Preoperative neurological status was associated with better postoperative McCormick score. PMID- 27656324 TI - Houston, GEMINI has landed: Spinal cord fusion achieved. PMID- 27656325 TI - GEMINI: Initial behavioral results after full severance of the cervical spinal cord in mice. AB - BACKGROUND: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, we report the preliminary data on the use of a fusogen [polyethylene glycol (PEG)] after full cervical cord transection in mice to facilitate the fusion of both ends of a sharply transected spinal cord. METHODS: Cervical laminectomy and a complete, visually confirmed cervical cord (C 5) transection was performed on female albino mice (n = 16). In Group 1 (n = 8), a fusogen, (PEG) was used to bridge the gap between the cut ends of the spinal cord. Group 2 received the same spinal cord transection but was treated with saline. Outcome was assessed daily using a standard scale (modified 22-point Basso-Beattie-Bresnahan scale) and filmed on camera. RESULTS: The PEG group (group 1) showed partial restoration of motor function after 4 weeks of observation; group 2 (placebo) did not recover any useful motor activity. CONCLUSION: In this preliminary experiment, PEG, but not saline, promoted partial motor recovery in mice submitted to full cervical transection. PMID- 27656326 TI - Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats. AB - BACKGROUND: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. METHODS: Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. RESULTS: While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. CONCLUSION: In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord. PMID- 27656327 TI - Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG. AB - BACKGROUND: A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. CASE DESCRIPTION: Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. CONCLUSION: While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs. PMID- 27656328 TI - Development of inCVAX, In situ Cancer Vaccine, and Its Immune Response in Mice with Hepatocellular Cancer. AB - Manipulation of immune system toward the rejection of established cancers has become the standard of care in some patients. Here we propose the development of an in situ autologous cancer vaccine, inCVAX, for the treatment of hepatocellular cancer (HCC). inCVAX is based on the induction of local immunogenic cancer cell death combined with local dendritic cell stimulation by intratumoral injection of the immune-activator N-dihydro-galacto-chitosan (GC). In a first set of experiments, cellular and molecular studies were performed to investigate the effect of inCVAX on immune activation in a murine model of HCC that we previously developed. Once large tumors were formed in mice, the tumor is surgically exposed and a laser fiber was inserted into the center of an individual tumor mass. Using a 10 mm diffuser tip, laser irradiation of 1.5 W was applied to heat the tumor at different durations (6-10 min) to assess tolerability of photothermal application at different temperatures. The laser application was followed by immediate injection of GC, and each mouse received one laser treatment and one GC injection. ELISA was used to assess the level of cytokines; immunohistochemical staining was conducted to analyze the effect of inCVAX on immune cell tumor filtration and expression of tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs). Results indicate that survival correlated to thermal exposure. At lower temperatures the photothermal effect was sufficient to induce tumor necrosis, but without obvious complication to the mice, although at these temperatures the treatment didn't alter the level of TSAs and TAAs, so further optimization is suggested. Nevertheless, in response to the inCVAX treatment, cytotoxic cytokine IFN-gamma was significantly increased, but suppressive cytokine TGF-beta was dramatically reduced. Furthermore, inCVAX prompted tumor infiltration of CD3+, CD4+, and CD8+ T cells; but modulated macrophage subsets differently. In conclusion, while the protocol needs further optimization, it would appear that inCVAX for the treatment of HCC activates an immune response in tumor-bearing mice, which in turn may have potential for the treatment of HCC. PMID- 27656329 TI - Vertical structure and physical processes of the Madden-Julian Oscillation: Biases and uncertainties at short range. AB - An analysis of diabatic heating and moistening processes from 12 to 36 h lead time forecasts from 12 Global Circulation Models are presented as part of the "Vertical structure and physical processes of the Madden-Julian Oscillation (MJO)" project. A lead time of 12-36 h is chosen to constrain the large-scale dynamics and thermodynamics to be close to observations while avoiding being too close to the initial spin-up of the models as they adjust to being driven from the Years of Tropical Convection (YOTC) analysis. A comparison of the vertical velocity and rainfall with the observations and YOTC analysis suggests that the phases of convection associated with the MJO are constrained in most models at this lead time although the rainfall in the suppressed phase is typically overestimated. Although the large-scale dynamics is reasonably constrained, moistening and heating profiles have large intermodel spread. In particular, there are large spreads in convective heating and moistening at midlevels during the transition to active convection. Radiative heating and cloud parameters have the largest relative spread across models at upper levels during the active phase. A detailed analysis of time step behavior shows that some models show strong intermittency in rainfall and differences in the precipitation and dynamics relationship between models. The wealth of model outputs archived during this project is a very valuable resource for model developers beyond the study of the MJO. In addition, the findings of this study can inform the design of process model experiments, and inform the priorities for field experiments and future observing systems. PMID- 27656330 TI - Frequency and causes of failed MODIS cloud property retrievals for liquid phase clouds over global oceans. AB - Moderate Resolution Imaging Spectroradiometer (MODIS) retrieves cloud droplet effective radius (re ) and optical thickness (tau) by projecting observed cloud reflectances onto a precomputed look-up table (LUT). When observations fall outside of the LUT, the retrieval is considered "failed" because no combination of tau and re within the LUT can explain the observed cloud reflectances. In this study, the frequency and potential causes of failed MODIS retrievals for marine liquid phase (MLP) clouds are analyzed based on 1 year of Aqua MODIS Collection 6 products and collocated CALIOP and CloudSat observations. The retrieval based on the 0.86 um and 2.1 um MODIS channel combination has an overall failure rate of about 16% (10% for the 0.86 um and 3.7 um combination). The failure rates are lower over stratocumulus regimes and higher over the broken trade wind cumulus regimes. The leading type of failure is the "re too large" failure accounting for 60%-85% of all failed retrievals. The rest is mostly due to the "re too small" or tau retrieval failures. Enhanced retrieval failure rates are found when MLP cloud pixels are partially cloudy or have high subpixel inhomogeneity, are located at special Sun-satellite viewing geometries such as sunglint, large viewing or solar zenith angles, or cloudbow and glory angles, or are subject to cloud masking, cloud overlapping, and/or cloud phase retrieval issues. The majority (more than 84%) of failed retrievals along the CALIPSO track can be attributed to at least one or more of these potential reasons. The collocated CloudSat radar reflectivity observations reveal that the remaining failed retrievals are often precipitating. It remains an open question whether the extremely large re values observed in these clouds are the consequence of true cloud microphysics or still due to artifacts not included in this study. PMID- 27656331 TI - The carbon dioxide system on the Mississippi River-dominated continental shelf in the northern Gulf of Mexico: 1. Distribution and air-sea CO2 flux. AB - River-dominated continental shelf environments are active sites of air-sea CO2 exchange. We conducted 13 cruises in the northern Gulf of Mexico, a region strongly influenced by fresh water and nutrients delivered from the Mississippi and Atchafalaya River system. The sea surface partial pressure of carbon dioxide (pCO2) was measured, and the air-sea CO2 flux was calculated. Results show that CO2 exchange exhibited a distinct seasonality: the study area was a net sink of atmospheric CO2 during spring and early summer, and it was neutral or a weak source of CO2 to the atmosphere during midsummer, fall, and winter. Along the salinity gradient, across the shelf, the sea surface shifted from a source of CO2 in low-salinity zones (0<=S<17) to a strong CO2 sink in the middle-to-high salinity zones (17<=S<33), and finally was a near-neutral state in the high salinity areas (33<=S<35) and in the open gulf (S>=35). High pCO2 values were only observed in narrow regions near freshwater sources, and the distribution of undersaturated pCO2 generally reflected the influence of freshwater inputs along the shelf. Systematic analyses of pCO2 variation demonstrated the importance of riverine nitrogen export; that is, riverine nitrogen-enhanced biological removal, along with mixing processes, dominated pCO2 variation along the salinity gradient. In addition, extreme or unusual weather events were observed to alter the alongshore pCO2 distribution and to affect regional air-sea CO2 flux estimates. Overall, the study region acted as a net CO2 sink of 0.96 +/- 3.7 mol m-2 yr-1 (1.15 +/- 4.4 Tg C yr-1). PMID- 27656332 TI - Altimeter-derived seasonal circulation on the southwest Atlantic shelf: 27 degrees -43 degrees S. AB - Altimeter sea surface height (SSH) fields are analyzed to define and discuss the seasonal circulation over the wide continental shelf in the SW Atlantic Ocean (27 degrees -43 degrees S) during 2001-2012. Seasonal variability is low south of the Rio de la Plata (RdlP), where winds and currents remain equatorward for most of the year. Winds and currents in the central and northern parts of our domain are also equatorward during autumn and winter but reverse to become poleward during spring and summer. Transports of shelf water to the deep ocean are strongest during summer offshore and to the southeast of the RdlP. Details of the flow are discussed using mean monthly seasonal cycles of winds, heights, and currents, along with analyses of Empirical Orthogonal Functions. Principle Estimator Patterns bring out the patterns of wind forcing and ocean response. The largest part of the seasonal variability in SSH signals is due to changes in the wind forcing (described above) and changes in the strong boundary currents that flow along the eastern boundary of the shelf. The rest of the variability contains a smaller component due to heating and expansion of the water column, concentrated in the southern part of the region next to the coast. Our results compare well to previous studies using in situ data and to results from realistic numerical models of the regional circulation. PMID- 27656333 TI - Distinguishing between pulsed and continuous reconnection at the dayside magnetopause. AB - Magnetic reconnection has been established as the dominant mechanism by which magnetic fields in different regions change topology to create open magnetic field lines that allow energy and momentum to flow into the magnetosphere. One of the persistent problems of magnetic reconnection is the question of whether the process is continuous or intermittent and what input condition(s) might favor one type of reconnection over the other. Observations from imagers that record FUV emissions caused by precipitating cusp ions demonstrate the global nature of magnetic reconnection. Those images show continuous ionospheric emissions even during changing interplanetary magnetic field conditions. On the other hand, in situ observations from polar-orbiting satellites show distinctive cusp structures in flux distributions of precipitating ions, which are interpreted as the telltale signature of intermittent reconnection. This study uses a modification of the low-velocity cutoff method, which was previously successfully used to determine the location of the reconnection site, to calculate for the cusp ion distributions the "time since reconnection occurred." The "time since reconnection" is used to determine the "reconnection time" for the cusp magnetic field lines where these distributions have been observed. The profile of the reconnection time, either continuous or stepped, is a direct measurement of the nature of magnetic reconnection at the reconnection site. This paper will discuss a continuous and pulsed reconnection event from the Polar spacecraft to illustrate the methodology. PMID- 27656334 TI - Global storm time depletion of the outer electron belt. AB - The outer radiation belt consists of relativistic (>0.5 MeV) electrons trapped on closed trajectories around Earth where the magnetic field is nearly dipolar. During increased geomagnetic activity, electron intensities in the belt can vary by orders of magnitude at different spatial and temporal scales. The main phase of geomagnetic storms often produces deep depletions of electron intensities over broad regions of the outer belt. Previous studies identified three possible processes that can contribute to the main-phase depletions: adiabatic inflation of electron drift orbits caused by the ring current growth, electron loss into the atmosphere, and electron escape through the magnetopause boundary. In this paper we investigate the relative importance of the adiabatic effect and magnetopause loss to the rapid depletion of the outer belt observed at the Van Allen Probes spacecraft during the main phase of 17 March 2013 storm. The intensities of >1 MeV electrons were depleted by more than an order of magnitude over the entire radial extent of the belt in less than 6 h after the sudden storm commencement. For the analysis we used three-dimensional test particle simulations of global evolution of the outer belt in the Tsyganenko-Sitnov (TS07D) magnetic field model with an inductive electric field. Comparison of the simulation results with electron measurements from the Magnetic Electron Ion Spectrometer experiment shows that magnetopause loss accounts for most of the observed depletion at L>5, while at lower L shells the depletion is adiabatic. Both magnetopause loss and the adiabatic effect are controlled by the change in global configuration of the magnetic field due to storm time development of the ring current; a simulation of electron evolution without a ring current produces a much weaker depletion. PMID- 27656335 TI - Modular model for Mercury's magnetospheric magnetic field confined within the average observed magnetopause. AB - Accurate knowledge of Mercury's magnetospheric magnetic field is required to understand the sources of the planet's internal field. We present the first model of Mercury's magnetospheric magnetic field confined within a magnetopause shape derived from Magnetometer observations by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft. The field of internal origin is approximated by a dipole of magnitude 190 nT RM3, where RM is Mercury's radius, offset northward by 479 km along the spin axis. External field sources include currents flowing on the magnetopause boundary and in the cross-tail current sheet. The cross-tail current is described by a disk-shaped current near the planet and a sheet current at larger (? 5 RM ) antisunward distances. The tail currents are constrained by minimizing the root-mean-square (RMS) residual between the model and the magnetic field observed within the magnetosphere. The magnetopause current contributions are derived by shielding the field of each module external to the magnetopause by minimizing the RMS normal component of the magnetic field at the magnetopause. The new model yields improvements over the previously developed paraboloid model in regions that are close to the magnetopause and the nightside magnetic equatorial plane. Magnetic field residuals remain that are distributed systematically over large areas and vary monotonically with magnetic activity. Further advances in empirical descriptions of Mercury's magnetospheric external field will need to account for the dependence of the tail and magnetopause currents on magnetic activity and additional sources within the magnetosphere associated with Birkeland currents and plasma distributions near the dayside magnetopause. PMID- 27656336 TI - What effect do substorms have on the content of the radiation belts? AB - Substorms are fundamental and dynamic processes in the magnetosphere, converting captured solar wind magnetic energy into plasma energy. These substorms have been suggested to be a key driver of energetic electron enhancements in the outer radiation belts. Substorms inject a keV "seed" population into the inner magnetosphere which is subsequently energized through wave-particle interactions up to relativistic energies; however, the extent to which substorms enhance the radiation belts, either directly or indirectly, has never before been quantified. In this study, we examine increases and decreases in the total radiation belt electron content (TRBEC) following substorms and geomagnetically quiet intervals. Our results show that the radiation belts are inherently lossy, shown by a negative median change in TRBEC at all intervals following substorms and quiet intervals. However, there are up to 3 times as many increases in TRBEC following substorm intervals. There is a lag of 1-3 days between the substorm or quiet intervals and their greatest effect on radiation belt content, shown in the difference between the occurrence of increases and losses in TRBEC following substorms and quiet intervals, the mean change in TRBEC following substorms or quiet intervals, and the cross correlation between SuperMAG AL (SML) and TRBEC. However, there is a statistically significant effect on the occurrence of increases and decreases in TRBEC up to a lag of 6 days. Increases in radiation belt content show a significant correlation with SML and SYM-H, but decreases in the radiation belt show no apparent link with magnetospheric activity levels. PMID- 27656337 TI - A Method for Simultaneous Determination of 25-Hydroxyvitamin D3 and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent. AB - A method for the simultaneous determination of 25-hydroxyvitamin D3 [25(OH)D3] and its 3-sulfate [25(OH)D3S] in newborn plasma, which is expected to be helpful in the assessment of the vitamin D status, using stable isotope-dilution liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been developed and validated. The plasma was pretreated based on the deproteinization and solid-phase extraction, then subjected to derivatization with 4-(4-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD). The derivatization enabled the accurate quantification of 25(OH)D3 without interference from 3-epi-25(OH)D3 and also facilitated the simultaneous determination of the two metabolites by LC/positive ESI-MS/MS. Quantification was based on the selected reaction monitoring with the characteristic fragmentation of the DAPTAD-derivatives during MS/MS. This method was reproducible (intra- and inter-assay relative standard deviations of 7.8% or lower for both metabolites) and accurate (analytical recovery, 95.4-105.6%). The limits of quantification were 1.0 ng/mL and 2.5 ng/mL for 25(OH)D3 and 25(OH)D3S, respectively, when using a 20-MUL sample. The developed method was applied to the simultaneous determination of plasma 25(OH)D3 and 25(OH)D3S in newborns; it was recognized that the plasma concentration of 25(OH)D3S is significantly higher than that of 25(OH)D3, and preterm newborns have lower plasma 25(OH)D3S concentrations than full-term newborns. PMID- 27656339 TI - Niche construction game cancer cells play. AB - Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology. PMID- 27656340 TI - Interaction between Ni and HZSM-5 in aromatization-enhanced reactive adsorption desulfurization catalysts for FCC gasoline upgrading. AB - A compound catalyst (RA) consisted of Ni, ZnO and HZSM-5 with functions of reactive adsorption desulfurization (RADS) and olefin aromatization for fluid catalytic cracking (FCC) gasoline upgrading was prepared. X-ray powder diffraction (XRD), temperature-programmed reduction and low-temperature N2 adsorption were used to characterize the properties of the catalysts. Performance evaluation by FCC gasoline was carried out, and the result showed that the catalyst RA performed well in desulfurization and aromatization. For comparison, RADS catalyst (represented by DS) consisted of Ni and ZnO and aromatization catalyst (represented by Ar) consisted of HZSM-5 were prepared, respectively. They were combined in different ways to help investigating interaction between Ni and HZSM-5. Performance evaluated by FCC gasoline showed that catalyst RA performed best in desulfurization with a slight octane number loss. Interaction between Ni and HZSM-5 is a significant factor which influences the performance of the catalyst. PMID- 27656341 TI - Multifunctional two-stage riser fluid catalytic cracking process. AB - This paper described the discovering process of some shortcomings of the conventional fluid catalytic cracking (FCC) process and the proposed two-stage riser (TSR) FCC process for decreasing dry gas and coke yields and increasing light oil yield, which has been successfully applied in 12 industrial units. Furthermore, the multifunctional two-stage riser (MFT) FCC process proposed on the basis of the TSR FCC process was described, which were carried out by the optimization of reaction conditions for fresh feedstock and cycle oil catalytic cracking, respectively, by the coupling of cycle oil cracking and light FCC naphtha upgrading processes in the second-stage riser, and the specially designed reactor for further reducing the olefin content of gasoline. The pilot test showed that it can further improve the product quality, increase the diesel yield, and enhance the conversion of heavy oil. PMID- 27656338 TI - Salicylic acid: old and new implications for the treatment of type 2 diabetes? AB - Efficacy of salicylic acid as a treatment for diabetes was first established well over a century ago. Antihyperglycaemic effects are thought to include improved peripheral insulin sensitivity and suppression of hepatic glucose production. For most of this period, the molecular mechanisms underlying these effects have been poorly understood and these are still a focus of considerable research, which is reviewed here. Antihyperglycaemic effects are observed only at much higher concentrations than analgesic, antipyretic and antithrombotic properties, suggesting that different targets underlie the antidiabetic aspects of salicylate pharmacology. In the 1950s, antihyperglycaemic responses were linked to mitochondrial uncoupling effects of the drug. Then at the beginning of this century, antihyperglycaemic effects were linked to anti-inflammatory effects of the drug on NF-kappaB signalling. More recently, new work suggests that direct activation of AMPK may contribute to antihyperglycaemic/antihyperlipidemic actions of salicylates. Better understanding of the mechanism of salicylate's anthyperglycaemic effects may ultimately accelerate the development of new drugs for human use. PMID- 27656342 TI - Characterization of nitrogen compounds in coker gas oil by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and Fourier transform infrared spectroscopy. AB - In this study, the classes and structures of nitrogen species in coker gas oil (CGO) are characterized by electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) combined with Fourier transform infrared (FT-IR) spectroscopy. The results demonstrate that the m/z of basic and non-basic nitrogen compounds ranges from 180 to 560 and from 200 to 460, respectively. Six basic nitrogen compounds, N1 (a molecule contains one nitrogen atom, similarly hereinafter), N1O1, N1O1S1, N1O2, N1S1, and N2, are identified by their positive-ion mass spectra, and four non-basic nitrogen compounds, N1, N1O1, N1S1, and N2, are characterized by their negative-ion mass spectra. Among these nitrogen compounds, the N1 class species are the most predominant. Combined with the data of ESI FT-ICR MS and FT-IR, the basic N1 class species are likely pyridines, naphthenic pyridines, quinolines, and benzoquinolines. The most non basic N1 class species are derivatives of benzocarbazole. The N2 class species are likely amphoteric molecules with pyridine and pyrrole core structures. PMID- 27656343 TI - Advances of two-stage riser catalytic cracking of heavy oil for maximizing propylene yield (TMP) process. AB - Two-stage riser catalytic cracking of heavy oil for maximizing propylene yield (TMP) process proposed by State Key Laboratory of Heavy oil Processing, China University of Petroleum, can remarkably enhance the propylene yield and minimize the dry gas and coke yields, and obtain high-quality light oils (gasoline and diesel). It has been commercialized since 2006. Up to now, three TMP commercial units have been put into production and other four commercial units are under design and construction. The commercial data showed that taking paraffinic based Daqing (China) atmospheric residue as the feedstock, the propylene yield reached 20.31 wt%, the liquid products yield (the total yield of liquefied petroleum gas, gasoline, and diesel) was 82.66 wt%, and the total yield of dry gas and coke was 14.28 wt%. Moreover, the research octane number of gasoline could be up to 96. PMID- 27656344 TI - Multi-scale CFD simulation of hydrodynamics and cracking reactions in fixed fluidized bed reactors. AB - Fixed fluidized bed reactor is widely used to evaluate the crackability of heavy oils and the activity of catalysts. To understand the hydrodynamics, reaction kinetics and thermodynamics in conventional and modified fixed fluidized bed reactors, the computational fluid dynamics method, energy-minimization multi scale-based two-fluid model coupled with a six-lump kinetic model was used to investigate the gas-solid flow and cracking reactions. The gas mixing and particle volume fraction distributions, as well as product yields in the conventional and modified fixed fluidized bed reactors were analyzed. The residence time distribution model was utilized to obtain the parameters indicating the back-mixing degree, such as mean residence time and dimensionless variance of the gas. The results showed that the simulated product distribution is in reasonable agreement with the experimental data; the modified fixed fluidized bed reactor is closer to the ideal plug flow reactor, which can efficiently enhance the gas-solid mixing, reduce the gas back-mixing degree, and hence improve the reaction performance. PMID- 27656345 TI - Retardation effect of nitrogen compounds and condensed aromatics on shale oil catalytic cracking processing and their characterization. AB - Untreated shale oil, shale oil treated with HCl aqueous solution and shale oil treated with HCl and furfural were used to do comparative experiments in fixed bed reactors. Nitrogen compounds and condensed aromatics extracted by HCl and furfural were characterized by electrospray ionization Fourier transform cyclotron resonance mass spectrometry and gas chromatography and mass spectrometry, respectively. Compared with untreated shale oil, the conversion and yield of liquid products increased considerably after removing basic nitrogen compounds by HCl extraction. Furthermore, after removing nitrogen compounds and condensed aromatics by both HCl and furfural, the conversion and yield of liquid products further increased. In addition, N1 class species are predominant in both basic and non-basic nitrogen compounds, and they are probably indole, carbazole, cycloalkyl-carbazole, pyridine and cycloalkyl-pyridine. As for the condensed aromatics, most of them possess aromatic rings with two to three rings and zero to four carbon atom. PMID- 27656347 TI - Preparation of mesophase pitch by aromatics-rich distillate of naphthenic vacuum gas oil. AB - Two aromatics-rich distillates R1 and R2 with different properties from naphthenic base vacuum gas oil were used for preparing mesophase pitch through high-pressure thermal treatment. 1H-NMR, FT-IR and VPO were employed to characterize the structural parameters of the raw materials. The products' optical texture and molecular structure were analyzed by polarized light optical microscopy, 1H-NMR, FT-IR and XRD. The effect of raw materials' structure on the formation of mesophase pitch was discussed. The results showed that the structure of the raw material had an important effect on the formation of mesophase pitch. The raw material R2 with higher aromaticity, more naphthenic structure and less alkyl side chains was easy to form mesophase pitch with large-domains optical texture, lower softening point and more ordered crystal structure. PMID- 27656346 TI - Vacuum ultraviolet photofragmentation of octadecane: photoionization mass spectrometric and theoretical investigation. AB - The photoionization and fragmentation of octadecane were investigated with infrared laser desorption/tunable synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry (IRLD/VUV PIMS) and theoretical calculations. Mass spectra of octadecane were measured at various photon energies. The fragment ions were gradually detected with the increase of photon energy. The main fragment ions were assigned to radical ions (C n H2n+1+, n = 4-11) and alkene ions (C n H2n+, n = 5-10). The ionization energy of the precursor and appearance energy of ionic fragments were obtained by measuring the photoionization efficiency spectrum. Possible formation pathways of the fragment ions were discussed with the help of density functional theory calculations. PMID- 27656348 TI - Desulfurization of Saudi Arabian crudes by oxidation-extraction method. AB - The oxidation-extraction desulfurization of Saudi Arabian crudes was conducted with hydrogen peroxide-acetic acid oxidation system. The selection of extractant, the optimization of oxidation-extraction conditions, and the exploration of desulfurization mechanism were studied. As DMF was used as the extractant, the optimal desulfurization rate of 35.11 % and oil recovery of 95 % were obtained at 70 degrees C with the molar ratio of peracetic acid to sulfur of 8:1, the molar ratio of acetic acid to hydrogen peroxide of 2:1 and the volume ratio of extractant to oil of 1:1. The desulfurization effect of different fractions in the treated Saudi Arabian crudes was found to obey the following order: gasoline diesel fraction >VGO fraction >VR fraction, due to different types and structures of sulfur compounds. The oil quality was less affected and most sulfides were mainly extracted via DMF. PMID- 27656349 TI - Effects of zinc incorporation on hierarchical ZSM-11 catalyst for methanol conversion. AB - ABSTRACT: Hierarchical ZSM-11 and Zn-ZSM-11 catalysts were used in this study. The effects of two methods (direct synthesis and impregnation) of zinc incorporation on methanol conversion were investigated in a continuous-flow isotherm fixed-bed reactor. XRD, SEM, BET, FTIR, and XRF analytical results revealed that the introduction of zinc through direct synthesis generated new Bronsted acid sites that could tune the ratio of light olefins. The damage to the framework structure after zinc incorporation restrained the aromatization, dehydrogenation, and decomposition of methanol. The extent of this impact determined the degree of deactivation behaviors. Thus, the yield of propene and butene was enhanced through the direct synthesis method (2 % ZnZ11-C, 4 % ZnZ11 C), and the sample 4 % ZnZ11-C displayed a fast deactivation. GRAPHICAL ABSTRACT: PMID- 27656351 TI - Acute Antibody-Mediated Rejection in Renal Transplantation: Current Clinical Management. AB - Acute antibody mediated rejection (AMR) is recognized as a major cause of graft loss in renal transplant recipients. Early acute AMR in the first few days after transplantation occurs primarily in sensitized renal transplant recipients with donor-specific alloantibody at the time of transplant and is a relatively "pure" form of acute AMR. Late acute AMR occurs months to years after transplantation and is commonly a mixed cellular and humoral rejection. While there is no consensus regarding optimum treatment, we contend that rational therapeutic approaches are emerging and the acute episode can be managed in most instances. However, new therapies are needed to prevent ongoing chronic injury in these patients. PMID- 27656350 TI - Risk perception in fire evacuation behavior revisited: definitions, related concepts, and empirical evidence. AB - Risk perception (RP) is studied in many research disciplines (e.g., safety engineering, psychology, and sociology). Definitions of RP can be broadly divided into expectancy-value and risk-as-feeling approaches. In the present review, RP is seen as the personalization of the risk related to a current event, such as an ongoing fire emergency; it is influenced by emotions and prone to cognitive biases. We differentiate RP from other related concepts (e.g., situation awareness) and introduce theoretical frameworks relevant to RP in fire evacuation (e.g., Protective Action Decision Model and Heuristic-Systematic approaches). Furthermore, we review studies on RP during evacuation with a focus on the World Trade Center evacuation on September 11, 2001 and present factors modulating RP as well as the relation between perceived risk and protective actions. We summarize the factors that influence perception risk and discuss the direction of these relationships (i.e., positive or negative influence, or inconsequential) and conclude with presenting limitations of this review and an outlook on future research. PMID- 27656352 TI - The red meat allergy syndrome in Sweden. AB - In the last decade, a novel type of food allergy presenting with severe allergic reactions several hours after consumption of red meat has been recognized. The allergic responses are due to IgE antibodies directed against the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-Gal) found in mammalian meat. This review presents the red meat allergy syndrome in Sweden, discusses the features of the immune response to carbohydrates, and highlights the presence of heat stable alpha-Gal-containing proteins in meat. The number of diagnosed red meat allergy cases in Sweden has increased significantly over the past few years. All patients have been tick bitten. Our recent work has shown that alpha-Gal is present in the European tick Ixodes ricinus (I. ricinus), thus potentially explaining the strong association between anti-alpha-Gal IgE and tick bites, with development of red meat allergy as a secondary phenomenon. Further studies using immunoproteomics have identified novel alpha-Gal-containing meat proteins that bound IgE from red meat allergic patients. Four of these proteins were stable to thermal processing pointing to the fact that the allergenicity of red meat proteins is preserved in cooked meat. In keeping with the fact that the alpha-Gal epitope is structurally related to the blood group B antigen, a positive association with the B-negative blood groups among our red meat allergic patients was noted. A selective IgE reactivity to the pure carbohydrate moiety was observed when investigating the specificity of the alpha-Gal immune response. IgE from red meat allergic patients does not recognize the other major mammalian carbohydrate, N-glycolylneuraminic acid (Neu5Gc), also present in high amounts in red meat. Furthermore, neither common cross-reactive carbohydrate determinants (CCDs) from plants nor venoms are targets of the IgE response in these patients. Taken together, the alpha-Gal carbohydrate has shown to be a potentially clinically relevant allergen that should be taken into account in the diagnosis of food allergy. Many new findings in the field of red meat allergy have been obtained during the past years, but further efforts to understand the process of digestion, absorption, and delivery of alpha-Gal-containing molecules to the circulation are needed. PMID- 27656353 TI - Coping with cross-reactive carbohydrate determinants in allergy diagnosis. AB - A relevant proportion of allergy diagnosis is accomplished by in vitro determination of specific immunglobulin E (sIgE) to extracts from suspected allergens. Such extracts inevitably contain glycoproteins, which may react with patients' IgE. In the case of plant and insect allergens, the relevant epitope structure is an alpha-1,3-fucose on the Asn-linked sugar residue of so-called N glycans. Due to their wide distribution, N-glycans carrying this epitope are known as "cross-reactive carbohydrate determinant(s)" (CCD[s]). About 15 years of awareness allow the conclusion that anti-CCD IgE does not cause noticeable clinical symptoms. In consequence, diagnostic results arising from CCD reactivity must be rated as false positives. With up to 30 % of CCD reactive patients, this can be regarded as a serious problem. Another cross-reactive carbohydrate determinant became notorious as a potential cause of anaphylactic reactions to a recombinant glycoprotein drug carrying alpha-1,3-galactose. This galactose containing determinant (GalCD, galactose containing cross-reactive carbohydrate determinant) was supposed as a trigger for delayed allergic reactions to red meat in several cases. Thus, alpha-1,3-galactose may have clinical relevance in certain cases - possibly as a result of tick bites. Often, however, GalCDs probably cause false-positive results with milk and meat extracts. No clear evidence for the role of other non-human carbohydrate structures such as N glycolylneuraminic acid as CCD has been presented so far. Remedies for sIgE based in vitro diagnosis come in the form of non-glycosylated recombinant allergen components or of specific CCD inhibitors. The high potential of recombinant allergens is optimally realized in the context of component resolved diagnosis using allergen arrays with more than 100 components, whereas CCD inhibitors increase the specificity of conventional extract-based diagnosis. Reagents for the detection and inhibition of CCDs from plants and insects have been developed, whereas tools for GalCDs of milk and meat lag behind. PMID- 27656355 TI - Texting while driving: A study of 1211 U.S. adults with the Distracted Driving Survey. AB - Texting and other cell-phone related distracted driving is estimated to account for thousands of motor vehicle collisions each year but studies examining the specific cell phone reading and writing activities of drivers are limited. The objective of this study was to describe the frequency of cell-phone related distracted driving behaviors. A national, representative, anonymous panel of 1211 United States drivers was recruited in 2015 to complete the Distracted Driving Survey (DDS), an 11-item validated questionnaire examining cell phone reading and writing activities and at what speeds they occur. Higher DDS scores reflect more distraction. DDS scores were analyzed by demographic data and self-reported crash rate. Nearly 60% of respondents reported a cell phone reading or writing activity within the prior 30 days, with reading texts (48%), writing texts (33%) and viewing maps (43%) most frequently reported. Only 4.9% of respondents had enrolled in a program aimed at reducing cell phone related distracted driving. DDS scores were significantly correlated to crash rate (p < 0.0001), with every one point increase associated with an additional 7% risk of a crash (p < 0.0001). DDS scores were inversely correlated to age (p < 0.0001). The DDS demonstrated high internal consistency (Cronbach's alpha = 0.94). High rates of cell phone related distraction are reported here in a national sample. Distraction is associated with crash rates and occurs across all age groups, but is highest in younger drivers. The DDS can be used to evaluate the impact of public health programs aimed at reducing cell-phone related distracted driving. PMID- 27656356 TI - Safety and clinical response of intraventricular caspofungin for Scedosporium apiospermum complex central nervous system infection. AB - We present a 71-year old woman treated with 14 days of 5 mg intraventricular caspofungin for Scedosporium apiospermum complex meningoencephalitis diagnosed after spinal fusion and instrumentation. Cerebrospinal fluid studies improved during therapy and intraventricular administration was well tolerated. Within weeks of discontinuation, the patient experienced clinical deterioration with disease progression. There are sparse data on the efficacy and safety of administering intraventricular caspofungin. While apparently safe, intraventricular caspofungin was insufficient for disease control in this case. PMID- 27656354 TI - Microbiota, regulatory T cell subsets, and allergic disorders. PMID- 27656357 TI - Diagnosis, Evaluation, and Endoscopic Repair of Partial Articular Gluteus Tendon Avulsion. AB - In addition to trochanteric bursitis, gluteus medius and minimus tears (GMMTs) can be a common source of insidious lateral hip pain and dysfunction. Partial thickness GMMTs are much more common than full-thickness GMMTs but are frequently overlooked by both radiologists and orthopaedic surgeons. GMMTs are commonly identified on magnetic resonance imaging ordered for lateral hip pain unresponsive to conservative management. Imaging can show that high-grade partial articular gluteus tendon avulsion (PAGTA) can occur as either an isolated gluteus medius tear, an isolated gluteus minimus tear, or a combined GMMT. We describe how to identify PAGTA injuries with intraoperative assessment and identification of the interval between the gluteus medius and minimus tendons to allow access to the PAGTA without violating the bursal side of the tendon. PAGTAs can be repaired arthroscopically by single- or double-row suture anchor fixation depending on the size of the tear. The purpose of this article is to guide orthopaedic surgeons in the recognition of PAGTA with magnetic resonance imaging and dynamic examination to allow for accurate repair of GMMTs. PMID- 27656358 TI - The "Sublabral Window" in Arthroscopic Posterior Shoulder Instability Surgery: Description of a Technique for Safe Posterior Glenoid Preparation. AB - Arthroscopic posterior labral repairs for posterior shoulder instability can be challenging. Preparation of the capsulolabral tissue and glenoid bony surface is critical. Iatrogenic injury to the articular cartilage and unwarranted truncation of the capsulolabral tissue are concerns during preparation. As a result, several techniques have been described to potentially avoid these complications. We describe an additional technique for improving access and preparing the capsulolabral tissue and glenoid surface through a "sublabral window." This technique approaches the posterior labrum and glenoid through an already established posterior portal and mitigates iatrogenic injury to the labrum and articular cartilage. The technique is rather simple and easily adaptable. PMID- 27656359 TI - Tendoscopic Double-Row Suture Bridge Peroneal Retinaculum Repair for Recurrent Dislocation of Peroneal Tendons in the Ankle. AB - Traumatic dislocation of peroneal tendons in the ankle is an uncommon lesion that mainly affects young adults. Unfortunately, most cases lead to recurrent dislocation of the peroneal tendons of the ankle (RPTD). Therefore, most cases need operative treatment. One of the most common operative procedures is superior peroneal retinaculum (SPR) repair. Recently, surgery for RPTD has been achieved with less invasive arthroscopic procedures. In this article, tendoscopic surgery for RPTD using a double-row suture bridge technique is introduced. This technique consists of debridement of the lateral aspect of the fibula under an intrasheath pseudo-cavity, suture anchor insertion into the fibular ridge, and reattachment of the SPR to the fibula using a knotless anchor screwed into the lateral aspect of the fibula. This technique mimics the double-row suture bridge technique for rotator cuff tear repair. The double-row suture bridge technique requires more surgical steps than the single-row technique, but it provides a wider bone-SPR contact surface and tighter fixation than the single-row technique. This procedure is an attractive option because it is less invasive and has achieved results similar to open procedures. PMID- 27656360 TI - Fibrin Scaffold as a Carrier for Mesenchymal Stem Cells and Growth Factors in Shoulder Rotator Cuff Repair. AB - With an increase in the aging population, rotator cuff tears are becoming more common. High failure rates with shoulder rotator cuff repair surgery have been persistent, prompting the introduction of biologic methods to promote healing. The aim of the present technique is to deliver stem cells and growth factors to the footprint of the repair site. A platelet-rich plasma (PRP) fibrin clot is used as a scaffold for the delivery of stem cells, by using PRP, to provide a source of growth factors, and platelet-poor plasma (PPP) as a source for fibrinogen for the matrix for the scaffold. In the second step, bone marrow is harvested from the proximal humerus, concentrated, and combined with the PRP and PPP. Using a customized device, we then activate the clotting process and transfer the scaffold containing the stem cells using a suture anchor onto the shoulder rotator cuff footprint. In an effort to promote healing, this technique reimplants autologous stem cells and growth factors into the operative site. This technique may serve as an alternative for typically used scaffolds such as collagen matrices or decellularized human dermis patches. PMID- 27656361 TI - Anterolateral Ligament Reconstruction Technique: An Anatomic-Based Approach. AB - Restoration of anteroposterior laxity after an anterior cruciate ligament reconstruction has been predictable with traditional open and endoscopic techniques. However, anterolateral rotational stability has been difficult to achieve in a subset of patients, even with appropriate anatomic techniques. Therefore, differing techniques have attempted to address this rotational laxity by augmenting or reconstructing lateral-sided structures about the knee. In recent years, there has been a renewed interest in the anterolateral ligament as a potential contributor to residual anterolateral rotatory instability in anterior cruciate ligament-deficient patients. Numerous anatomic and biomechanical studies have been performed to further define the functional importance of the anterolateral ligament, highlighting the need for surgical techniques to address these injuries in the unstable knee. This article details our technique for an anatomic anterolateral ligament reconstruction using a semitendinosus tendon allograft. PMID- 27656362 TI - The Mayo Table Technique in Hip Arthroscopy. AB - Hip distractor devices or hip fracture tables (HFTs) are vital to perform a reliable hip arthroscopy (HA) for the treatment of femoroacetabular impingement, especially when labral tears, chondral-labral delaminations, ligamentum teres tears, and other intraarticular disorders are present. Adequate hip distractors were not available in the early days of HA; most of HFTs being used those days were rigid, cumbersome, and did not allow us to properly perform an arthroscopic dynamic impingement test to evaluate and assess the femoral head and its site of impingement. The mayo table technique was developed because of the lack of appropriate hip instrumentation and an HFT when the author (A.P.S.) started to perform HA. This easy technique allows the surgeon to control hip maximal range of motion and also to assess completely the cam deformity in the posterolateral, superolateral, anterior, and anteroinferior aspects. It also allows the surgeon to revise where the cam is impinging and afterward perform a complete bony resection and decompression. We strongly believe that with the mayo table technique HA can be performed simply and reliably in old rigid and cumbersome HFTs and also hip distractors that do not allow an adequate dynamic assessment of the hip with maximal range of motion. PMID- 27656363 TI - Endoscopic Loose Body Removal From Zone 2 Flexor Hallucis Longus Tendon Sheath. AB - Tenosynovial chondromatosis can occur in the flexor hallucis longus tendon sheath. Complete synovectomy and removal of the loose bodies comprise the treatment of choice. An open procedure requires extensive soft-tissue dissection because the flexor hallucis longus tendon is a deep structure except at the hallux. A tendoscopy approach to synovectomy and removal of loose bodies has the advantage of minimally invasive surgery. This technical note outlines pearls and pitfalls and provides a step-by-step guide to performing this procedure. PMID- 27656364 TI - Arthroscopic Reinsertion of Lateral Collateral Ligament, Anterior Capsular Plication, and Coronoid Tunneling Technique for Chronic Elbow Posterolateral Rotatory Instability. AB - Posterolateral rotatory instability (PLRI) of the elbow is a chronic condition that results from lateral collateral ligament complex injury and presents with pain, clicking, and subluxation within the flexion and extension arcs of elbow motion. The primary cause involves a lesion of the lateral collateral ligament complex and its avulsion from the lateral epicondyle. In most cases, it is the result of trauma such as a fall on an outstretched hand or any other mechanism that imparts axial compression, valgus force, and supination. Several surgical techniques have been described for the treatment of PLRI, but there is no consensus regarding the ideal surgical treatment. The advantages of an arthroscopic approach for the treatment of PLRI are first diagnostic. Arthroscopy allows for visualization and diagnosis of every compartment of the elbow. The main steps of the surgical procedure consist of reinsertion of the lateral collateral ligament, anterior capsular plication, and coronoid tunneling. By use of this technique, it is possible to perform an anatomic repair and provide stability of the elbow. PMID- 27656365 TI - Arthroscopic Microfracture for Osteochondritis Dissecans Lesions of the Capitellum. AB - Capitellar osteochondritis dissecans (OCD) is one of the most common causes of elbow pain and dysfunction in adolescent athletes. It typically occurs in gymnasts and overhead throwers and presents along a wide spectrum of severity. Stable lesions can typically be treated with conservative therapy; however, those presenting with instability, fragmentation, or loose bodies generally require surgical intervention. Although there are a number of described surgical options used to treat capitellar OCD lesions, microfracture is one of the most commonly performed and well studied. Patients who are candidates for microfracture generally have favorable outcomes with high rates of return to athletic activity after postoperative rehabilitation. In this work, we present our preferred arthroscopic technique for microfracture of OCD lesions of the capitellum. This technique is most suitable for patients with unstable or fragmented OCD lesions that are less than 1 cm in diameter and do not violate the lateral-most articular margin of the capitellum. PMID- 27656366 TI - Ultrasound-Assisted Endoscopic Carpal Tunnel Release. AB - Various surgical procedures for carpal tunnel syndrome exist, such as open release, ultrasound-guided percutaneous release, and endoscopic release. Postoperative pain, scarring, and slow recovery to normal function are reported complications of open release. Damage to vessels and the median nerve and its branches underlying the transverse carpal ligament is a reported complication of ultrasound-guided percutaneous release. Damage to the superficial palmar arch and incomplete release are reported complications of endoscopic release. By performing endoscopic carpal tunnel release with ultrasound assistance, we could visualize neurovascular structures directly with the endoscope and also indirectly with ultrasound to minimize complications. We could also evaluate the morphologic changes of the median nerve dynamically before and after the release. We discuss the technique for this procedure and outline pearls and pitfalls for success. PMID- 27656367 TI - Endoscopic Resection of the Lateral Ankle Bursa With Synovial Chondromatosis. AB - Bursal chondromatosis is synovial chondromatosis of the bursae. It is a rare disease entity that can involve the adventitial bursa of the lateral ankle. Complete synovectomy, removal of loose bodies, and bursectomy comprise the treatment of choice. Detailed preoperative radiologic assessment and surgical planning are the keys to success. Any accompanying synovial chondromatosis of the ankle or subtalar joint or tenosynovial chondromatosis of the peroneal tendon sheath should be treated together with the bursectomy. Endoscopic bursectomy can be performed through the bursal portal. The proximal and distal peroneal tendoscopy portals serve as viewing portals. The resection of the diseased tissues should be performed in a step-by-step zonal manner. Complete synovectomy and removal of loose bodies should be performed before bursectomy. Internal drainage of the bursal sac into the peroneal tendon sheath may be indicated if the sac is adherent to the skin. It should only be performed after complete synovectomy and removal of loose bodies. PMID- 27656368 TI - Arthroscopic Posteromedial Capsular Release. AB - Post-traumatic or postsurgical flexion contractures of the knee can significantly limit function and lead to gait abnormalities. In this setting, interventions to regain full extension may include bracing, physical therapy, and open or arthroscopic surgery. Open surgical approaches to restore full motion often demand extensive recovery and promote further adhesions and loss of motion, which has led to the advent of arthroscopic techniques to address these pathologies. We present a safe, effective, and reproducible arthroscopic technique for posteromedial capsular release to address knee flexion contractures. PMID- 27656369 TI - Arthroscopic All-Inside Posterior Cruciate Ligament Reconstruction: Overcoming the "Killer Turn". AB - One of the most challenging arthroscopic surgical procedures is posterior cruciate ligament (PCL) reconstruction. PCL injuries account for 20% of all knee ligament-related injuries. These may be isolated or occur as part of poly ligament injuries. With the possibility of PCL reconstruction with the all-inside technique, there has been a surge in interest in treating PCL injuries. With the PCL being one of the strongest ligaments in the body and a primary restraint to posterior translation of the tibia, the need for PCL reconstruction is being more and more recognized. Surgeons often find it difficult to negotiate the so-called killer turn while attempting arthroscopic PCL reconstruction. We describe the use of the GraftLink graft construct through the posteromedial portal in 7 patients (6 male and 1 female patient) with isolated PCL injuries, which we believe not only allows us to perform the all-inside PCL reconstruction but also does away with the difficulty of the killer turn encountered while performing the arthroscopic PCL reconstruction. PMID- 27656370 TI - A Fluoroscopy-Free Technique for Percutaneous Screw Positioning During Arthroscopic Treatment of Depression Tibial Plateau Fractures. AB - This article aims to describe a simple and reliable technique that helps in positioning the cannulated percutaneous screws during fixation of depression-type tibial plateau fractures. After fracture reduction under arthroscopic control, an outside-in anterior cruciate ligament femoral guide is introduced through the tibial cortical metaphyseal window and positioned under endoscopic control just underneath the elevated fragment. When proper height is achieved, a guide pin is drilled from lateral to medial through the sleeve, 1 to 2 cm distal to the articular surface of the depressed fragment. The cannulated screw can then be introduced under endoscopic control, without fluoroscopic assistance, just under the previously elevated joint surface. This technique ensures optimal placement of the cannulated screw in the middle of the bony tunnel to obtain optimal subchondral bone support during fixation of the depressed tibial plateau fracture. PMID- 27656371 TI - First Metatarsophalangeal Joint Arthroscopy for Osteochondral Lesions. AB - Small-joint arthroscopy has supplanted open procedures because it offers the potential for improvement in joint visualization, reduced scarring, and accelerated recovery. Despite these advantages, arthroscopy of the first metatarsophalangeal joint is not commonly performed and reports of its use are lacking. The reason for this is not clear but may be because of perceived technical complexity and poorly defined indications. In our experience, however, arthroscopy of the first metatarsophalangeal joint is a versatile procedure that facilitates treatment of many different pathologic processes through a minimally invasive approach with few complications. We present our technique for arthroscopic management of osteochondral lesions of the hallux. PMID- 27656372 TI - Ulnar Collateral Ligament Reconstruction of the Elbow: The Docking Technique. AB - Reconstruction of the ulnar collateral ligament (UCL) is one of the most commonly performed surgical procedures in overhead throwing athletes. Since its initial description, the procedure has undergone a number of technical modifications and advancements. This has resulted in multiple described techniques for UCL reconstruction. One of the most commonly performed UCL reconstruction methods is the docking technique. It has the advantages of minimizing injury to the flexor pronator mass, avoiding the ulnar nerve, allowing robust graft tensioning, and reducing the amount of bone removed from the medial epicondyle compared with previously described techniques. This article provides a detailed description and video demonstration of how to perform this technique. When precise surgical steps are followed and postoperative rehabilitation appropriately progresses, this procedure has a well-documented history of reliably returning athletes to competitive throwing. PMID- 27656374 TI - Anterolateral Biplanar Proximal Tibial Opening-Wedge Osteotomy. AB - Proximal tibial anterolateral opening-wedge osteotomies have been reported to achieve successful biplanar lower-extremity realignment. Indications for a proximal tibial anterolateral osteotomy include symptomatic genu recurvatum with genu valgus alignment, usually in patients with a flat sagittal-plane tibial slope. The biplanar approach is able to simultaneously address both components of a patient's malalignment with a single procedure. The correction amount is verified with spacers and intraoperative imaging, while correction of the patient's heel height is simultaneously measured. A plate is secured into the osteotomy site, and the site is filled with bone allograft. The anterolateral tibial osteotomy has been reported to be an effective surgical procedure for correcting concomitant genu recurvatum and genu valgus malalignment. PMID- 27656373 TI - Chronic Distal Biceps Repair With an Achilles Allograft. AB - In cases of chronic distal biceps ruptures, the combination of muscle atrophy, distal tendon retraction, and fibrosis makes primary anatomic reattachment of the tendon particularly challenging. To regain tendon length and avoid flexion contractures, reconstruction with graft augmentation has been proposed as an alternative for cases not amenable to primary repair. We describe our technique using an Achilles allograft through a modified Henry approach to reconstruct the distal biceps tendon to regain length as well as restore flexion and supination strength. With proper and detailed exposure, chronic distal biceps injuries can be reconstructed safely and efficaciously using an Achilles allograft. PMID- 27656375 TI - Free Bone Plug Quadriceps Tendon Harvest and Suspensory Button Attachment for Anterior Cruciate Ligament Reconstruction. AB - The most commonly used autografts for anterior cruciate ligament reconstruction are the bone-patellar tendon-bone and hamstring tendons. Each has its advantages and limitations. The bone-patellar tendon-bone autograft can lead to more donor site morbidity, and the hamstring autograft can be unpredictable in size. The quadriceps tendon, with or without a bone block, has been described as an alternative graft source and has been used especially in revision cases, but in recent years, it has attracted attention even for primary cases. We report a technique for harvesting a free bone quadriceps tendon graft and attaching an extracortical button for femoral fixation for anterior cruciate ligament reconstruction. PMID- 27656376 TI - Proximal Rectus Femoris Avulsion Repair. AB - Proximal rectus femoris tendon avulsions are rare and occur mostly in male athletes. Currently, the standard of care for complete tendinous avulsions of the direct arm of the rectus femoris is nonoperative treatment. However, surgical repair may be considered in high-level athletes who have a high demand for repetitive hip flexion performed in an explosive manner or in patients in whom nonoperative treatment has failed. The purpose of this technical note is to describe the method for surgical repair of the proximal direct arm of the rectus femoris to its origin at the anterior inferior iliac spine using suture anchors. PMID- 27656377 TI - Posterior Wall Blowout During Anterior Cruciate Ligament Reconstruction: Suspensory Cortical Fixation With a Screw and Washer Post. AB - Posterior wall blowout can be a devastating intraoperative complication in anterior cruciate ligament reconstruction. This loss of osseous containment can cause difficulty with graft fixation and can potentially lead to early graft failure if unrecognized and left untreated. If cortical blowout occurs despite careful planning and proper surgical technique, a thorough knowledge of the local anatomy and surgical salvage options is paramount to ensure positive patient outcomes. This article highlights our preferred salvage technique using suspensory cortical fixation with a screw and washer construct. PMID- 27656379 TI - Anatomic Posterolateral Corner Reconstruction. AB - Posterolateral corner injuries represent a complex injury pattern, with damage to important coronal and rotatory stabilizers of the knee. These lesions commonly occur in association with other ligament injuries, making decisions regarding treatment challenging. Grade III posterolateral corner injuries result in significant instability and have poor outcomes when treated nonoperatively. As a result, reconstruction is advocated. A thorough knowledge of the anatomy is essential for surgical treatment of this pathology. The following technical note provides a diagnostic approach, postoperative management, and details of a technique for anatomic reconstruction of the 3 main static stabilizers of the posterolateral corner of the knee. PMID- 27656378 TI - Treatment of Midshaft Clavicle Fractures: Application of Local Autograft With Concurrent Plate Fixation. AB - Currently, open reduction-internal fixation using contoured plates or intramedullary nails is considered the standard operative treatment for midshaft clavicle fractures because of the immediate rigid stability provided by the fixation device. In addition, autologous iliac crest bone graft has proved to augment osteosynthesis during internal fixation of nonunion fractures through the release of osteogenic factors. The purpose of this article is to describe a surgical technique developed to reduce donor-site morbidity and improve functional and objective outcomes after open reduction-internal fixation with autologous bone graft placement through local autograft harvesting and concurrent plate fixation. PMID- 27656380 TI - The Arthroscopic Hill-Sachs Remplissage: A Technique Using a PASTA Repair Kit. AB - The arthroscopic remplissage procedure has gained popularity in recent years and is gaining acceptance as an excellent and safe procedure to perform in patients with large engaging Hill-Sachs lesions. The procedure was introduced as an arthroscopic procedure, but surgeons not familiar with the procedure often encounter many problems, which makes the procedure difficult and frustrating to perform. A technique for this procedure using a commercially available PASTA (partial articular supraspinatus tendon avulsion) repair kit is presented. PMID- 27656381 TI - Combined Reconstruction of the Medial Collateral Ligament and Anterior Cruciate Ligament Using Ipsilateral Quadriceps Tendon-Bone and Bone-Patellar Tendon-Bone Autografts. AB - The exclusive autograft choice for medial collateral ligament (MCL) reconstruction that has been described until today is the semitendinosus tendon. However, this has some potential disadvantages in a knee with combined MCL anterior cruciate ligament (ACL) injury, including weakening of the hamstring's anterior restraining action in an already ACL-injured knee and nonanatomic distal MCL graft insertion when leaving the semitendinosus insertion intact at the pes anserinus during reconstruction. Moreover, because some surgeons prefer to use the hamstring for autologous ACL reconstruction, the contralateral uninjured knee hamstring needs to be harvested as a graft source for the MCL reconstruction if autografts and not allografts are the surgeons' preference. We describe a technique for performing combined reconstruction of the MCL and ACL using ipsilateral quadriceps tendon-bone and bone-patellar tendon-bone autografts. This technique of MCL reconstruction spares the hamstring tendons and benefits from the advantage provided by bone-to-bone healing on the femur with distal and proximal MCL tibial fixation that closely reproduces the native MCL tibia insertion. PMID- 27656382 TI - Endoscopic Decompression of the First Branch of the Lateral Plantar Nerve and Release of the Plantar Aponeurosis for Chronic Heel Pain. AB - Entrapment of the first branch of the lateral plantar nerve is a commonly missed cause of recalcitrant plantar heel pain. The diagnosis is made on a clinical ground with maximal tenderness at the site of nerve entrapment. Treatment of the nerve entrapment is similar to that for plantar fasciitis, with rest, activity modification, nonsteroidal anti-inflammatory drugs, stretching exercise, and local steroid injection. Surgical release of the deep abductor hallucis fascia is indicated when conservative treatment failed. Endoscopic release of the nerve through the dorsal and plantar portals, as well as endoscopic plantar aponeurosis release, is a feasible approach. PMID- 27656383 TI - A Medial Meniscal Root Pullout Repair With the Use of a Tibial Tunnel Suturing Technique. AB - A meniscal root tear is one of the common knee injuries that can lead to degenerative changes in the knee joint. Meniscal root repairs can restore proper biomechanics of the knee joint. We have developed a suturing technique that uses a tibial tunnel for a pullout suture medial meniscal root repair. This is a straightforward technique that helps to promote simple suturing of the medial meniscal root, avoid iatrogenic injuries to the articular cartilage, and produce an additional working portal during a meniscal root repair. PMID- 27656384 TI - Surgical Technique: Arthroscopic Osteoplasty of Anterior Inferior Iliac Spine for Femoroacetabular Impingement. AB - The anterior inferior iliac spine (AIIS) has variable morphology that correlates with hip range of motion. Subspinal impingement is an extracapsular cause for femoroacetabular impingement (FAI) and is clinically significant because it results in decreased range of motion and groin pain with flexion-based activity. In symptomatic patients with AIIS extension to or below the acetabular rim, AIIS decompression is considered part of an FAI corrective procedure. A consistent exposed bony area on the anterior and inferomedial aspect of the AIIS serves as a "safe zone" of resection allowing for decompression with preservation of the origin of the rectus femoris tendon. This surgical note describes a technique for AIIS decompression. The goal for low AIIS osteoplasty is to resect the AIIS to 2 burr widths (using a 5.5-mm burr) above the acetabular rim, achieving an 11-mm clearance, creating a type I AIIS. The resultant flat anterior acetabular surface between the most anteroinferior prominent point of the AIIS and the acetabular rim allows for free movement of the hip joint without impingement. Careful execution of AIIS decompression can alleviate clinical symptoms of FAI and restore function to the hip joint. PMID- 27656386 TI - Core Decompression Augmented With Autologous Bone Marrow Aspiration Concentrate for Early Avascular Necrosis of the Femoral Head. AB - Lack of necessary perfusion to the femoral head can lead to necrosis of the underlying bone (avascular necrosis) and result in femoral and acetabular surface changes in advanced stages. Numerous treatments have been reported in the literature, including nonoperative and surgical procedures. In addition to the standard core decompression, we describe the use of bone marrow aspirate to stimulate a healing response and bone grafting, allowing for immediate weight bearing postoperatively. The purpose of this article was to describe our method of core decompression augmented with bone marrow aspirate concentrate and bone grafting for the treatment of early avascular necrosis of the femoral head. PMID- 27656385 TI - All-Arthroscopic Latissimus Dorsi Transfer. AB - Massive irreparable rotator cuff tears are often associated with severe functional impairment and disabling pain. One viable treatment option is a latissimus dorsi tendon transfer. We propose an all-arthroscopic technique that we believe avoids insult to the deltoid musculature while reducing morbidity from open harvest of the tendon. The operation is performed with the patient in the lateral decubitus position, by use of a combination of viewing and working portals in the axilla. The initial viewing portal is placed along the anterior belly of the latissimus muscle in the axilla. The latissimus and teres major are identified, as is the thoracodorsal neurovascular pedicle. The tendons are carefully separated, and the inferior and superior borders of the latissimus are whipstitched using a suture passer, which helps facilitate subsequent mobilization of the muscle. The interval deep to the deltoid and superficial to the teres minor is developed into a subdeltoid tunnel for arthroscopic tendon transfer. The latissimus tendon is then transferred and stabilized arthroscopically to the supraspinatus footprint with suture anchors. Our preliminary data suggest that this surgical technique results in improvement in pain, range of motion, and function. PMID- 27656387 TI - Endoscopic Repair of the Superficial Deltoid Ligament and Spring Ligament. AB - The plantar calcaneonavicular ligament, also known as the spring ligament, is an important static stabilizer of the medial longitudinal foot arch. Compromise of this ligament is a primary causative factor of peritalar subluxation, and it should be repaired in addition to treatment of tibialis posterior tendon abnormalities. Open repair of the ligament requires extensive soft-tissue dissection. The development of the high distal portal for posterior tibial tendoscopy allows repair of the ligament endoscopically. This, together with endoscopically assisted reconstruction of the tibialis posterior tendon, allows complete endoscopic treatment of stage 2 posterior tibial tendon deficiency. The major structure at risk is the medial plantar nerve. This technique is technically demanding and should be reserved for experienced foot and ankle arthroscopists. PMID- 27656388 TI - Calcaneal Ossoscopy. AB - Both unicameral bone cysts and intraosseous lipoma of the calcaneus are rare entities that are mostly diagnosed because of unspecific heel pain, pathologic fracture, or as incidental finding. Minimally invasive ossoscopy with endoscopic resection of the tumor followed by grafting can potentially minimize risks of open surgery and speed up convalescence. We present our modifications to previously described techniques of endoscopic curettage with a particular focus on intraosseous lipoma and allogenic grafting. The key point for grafting is the use of a funnel-shaped ear speculum facilitating the plombage with allogenic cancellous bone chips. Compared with its alternatives, grafting with allogenic cancellous bone might prove favorable in this localization for several reasons: osteointegration, handling, availability, and costs. The objective of this technical note is to present a simple, safe, and cost-effective surgical technique for endoscopic surgical treatment of benign osteolytic lesions of the calcaneus. PMID- 27656389 TI - Arthroscopic Autologous Chondrocyte Transplantation for Osteochondritis Dissecans of the Elbow. AB - Osteochondritis dissecans of the humeral capitellum is characterized by separation of a circumscript area of the articular surface and the subchondral bone in juvenile patients. In advanced lesions, arthroscopic fragment refixation or fragment removal with microfracturing or drilling can be successful. The purpose of this technical note is to describe an all-arthroscopic surgical technique for 3-dimensional purely autologous chondrocyte transplantation for osteochondral lesions of the humeral capitellum. PMID- 27656390 TI - Endoscopic Sciatic Nerve Decompression in the Prone Position-An Ischial-Based Approach. AB - Deep gluteal syndrome is described as sciatic nerve entrapment in the region deep to the gluteus maximus muscle. The entrapment can occur from the piriformis muscle, fibrous bands, blood vessels, and hamstrings. Good clinical outcomes have been shown in patients treated by open and endoscopic means. Sciatic nerve decompression with or without piriformis release provides a surgical solution to a difficult diagnostic and therapeutic problem. Previous techniques have used open methods that can now performed endoscopically. The technique of an endoscopic approach to sciatic nerve decompression in the prone position is described as well as its advantages and common findings. Through this ischial based approach, a familiar anatomy is seen and areas of sciatic nerve entrapment can be readily identified and safely decompressed. PMID- 27656391 TI - Endoscopically Assisted Anterior Subcutaneous Transposition of Ulnar Nerve. AB - Ulnar nerve compression at the elbow is the most common neuropathy of the upper extremity. Surgical options include in situ decompression, decompression with anterior transposition of the ulnar nerve, and medial epicondylectomy with or without decompression. With the advancement of endoscopic surgery, techniques of endoscopic in situ decompression of the ulnar nerve and endoscopic anterior transposition of ulnar nerve have been reported. This article describes a technique of endoscopically assisted anterior subcutaneous transposition of ulnar nerve that is composed of an open release and mobilization of the ulnar nerve at and distal to the cubital tunnel and endoscopic release and mobilization of the ulnar nerve proximal to the cubital tunnel. PMID- 27656392 TI - Reconstruction of the Medial Patellofemoral Ligament With Arthroscopic Control of Patellofemoral Congruence Using Electrical Stimulation of the Quadriceps. AB - Reconstruction of the medial patellofemoral ligament (MPFL) for recurrent patellar dislocation provides significant improvements in knee function. However, various complications have been reported, with most attributed to incorrect positioning of anchoring sites for the reconstructed MPFL and inappropriate graft tension. Patellofemoral congruence at 30 degrees of flexion on arthroscopy was therefore controlled using devices able to modify the length of the reconstructed MPFL. This was done under circumstances of external rotation of the knee joint and electrical stimulation of the quadriceps with the purpose of maintaining the patella in a lateral shift. Advantages of this technique include completely controllable correction on arthroscopy under the worst patellofemoral congruence induced by external rotation of the knee joint and electrical stimulation of the quadriceps at 30 degrees of flexion of the knee joint; in other words, voluntary determination of lateral shift during arthroscopy. PMID- 27656393 TI - Anatomic Hip Capsular Reconstruction With Separate Suture Anchors. AB - The number of reports on the use of capsule suturing techniques during hip arthroscopy has increased in the last few years because of the important function played by the iliofemoral ligament (IFL). This study describes an arthroscopic technique whereby the hip capsule is opened by a limited vertical dissection of both the capsule itself and the IFL from their footprint on the acetabular rim, and the capsulolabral junction and the IFL's deep fibers are released. After the intra-articular procedure, the capsule is closed through 2 to 4 side-to-side sutures in the vertical arm of the capsulotomy and 1 to 2 suture anchors with sutures are passed through either side of the capsular confluence. This technique prevents a full transverse section of the IFL and allows complete capsular closure through reconstruction of the capsular footprint. PMID- 27656394 TI - Arthroscopic Distal Clavical Resection Using "Vis-a-Vis" Portal. AB - Arthroscopic distal clavicle resection has become an increasingly popular procedure in orthopaedics, and various techniques have been published. Many of the arthroscopic distal clavicle resection techniques that have been reported require visualization from the lateral portal with an anterior working portal to perform the resection. While these techniques have reported high success rates, there is often difficulty in viewing the entire acromioclavicular joint from the 2 standard arthroscopic portals (lateral and anterior). This is due to the medial edge of the acromion blocking the ability to visualize the most superior and posterior portions of the distal clavicle. We propose a technique for arthroscopic distal clavicle resection using an accessory anterior portal. PMID- 27656395 TI - Arthroscopic Technique for Acetabular Labral Reconstruction Using Iliotibial Band Autograft. AB - The dynamic function of the acetabular labrum makes it an important structure for both hip stability and motion. Because of this, injuries to the labrum can cause significant dysfunction, leading to altered hip kinematics. Labral repair is the gold standard for symptomatic labral tears to keep as much labral tissue as possible; however, in cases where the labrum has been injured to such a degree that it is either deficient or repair is not possible, arthroscopic labral reconstruction is preferred. This article describes our preferred approach for reconstruction of the acetabular labrum using iliotibial band autograft. PMID- 27656396 TI - Anterior Meniscal Root Repair Using a Transtibial Double-Tunnel Pullout Technique. AB - The menisci are important structures within the knee and play a critical role in maintaining proper stability, load distribution, and joint lubrication. Injury to these structures can significantly alter the complex biomechanics of the knee and thus affect the health and longevity of the joint. Meniscal root tears are increasingly recognized as an important pathologic condition that results in a nonfunctional meniscus if not properly repaired. Whereas early treatment of meniscal tears traditionally focused on removal of the injured tissue, recent attention on the long-term consequences of partial or total meniscectomy has led to increased attempts at meniscal repair whenever possible. This article details our anatomic anterior root repair procedure using a transtibial double-tunnel pullout technique. PMID- 27656397 TI - Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood. AB - BACKGROUND: Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. SCOPE OF REVIEW: Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. MAJOR CONCLUSIONS: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders. PMID- 27656398 TI - An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion. AB - OBJECTIVE: Transport of pyruvate into the mitochondrial matrix by the Mitochondrial Pyruvate Carrier (MPC) is an important and rate-limiting step in its metabolism. In pancreatic beta-cells, mitochondrial pyruvate metabolism is thought to be important for glucose sensing and glucose-stimulated insulin secretion. METHODS: To evaluate the role that the MPC plays in maintaining systemic glucose homeostasis, we used genetically-engineered Drosophila and mice with loss of MPC activity in insulin-producing cells. RESULTS: In both species, MPC deficiency results in elevated blood sugar concentrations and glucose intolerance accompanied by impaired glucose-stimulated insulin secretion. In mouse islets, beta-cell MPC-deficiency resulted in decreased respiration with glucose, ATP-sensitive potassium (KATP) channel hyperactivity, and impaired insulin release. Moreover, treatment of pancreas-specific MPC knockout mice with glibenclamide, a sulfonylurea KATP channel inhibitor, improved defects in islet insulin secretion and abnormalities in glucose homeostasis in vivo. Finally, using a recently-developed biosensor for MPC activity, we show that the MPC is rapidly stimulated by glucose treatment in INS-1 insulinoma cells suggesting that glucose sensing is coupled to mitochondrial pyruvate carrier activity. CONCLUSIONS: Altogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia. PMID- 27656399 TI - miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function. AB - OBJECTIVE: In rodents and humans, besides brown adipose tissue (BAT), islands of thermogenic adipocytes, termed "brite" (brown-in-white) or beige adipocytes, emerge within white adipose tissue (WAT) after cold exposure or beta3 adrenoceptor stimulation, which may protect from obesity and associated diseases. microRNAs are novel modulators of adipose tissue development and function. The purpose of this work was to characterize the role of microRNAs in the control of brite adipocyte formation. METHODS/RESULTS: Using human multipotent adipose derived stem cells, we identified miR-125b-5p as downregulated upon brite adipocyte formation. In humans and rodents, miR-125b-5p expression was lower in BAT than in WAT. In vitro, overexpression and knockdown of miR-125b-5p decreased and increased mitochondrial biogenesis, respectively. In vivo, miR-125b-5p levels were downregulated in subcutaneous WAT and interscapular BAT upon beta3 adrenergic receptor stimulation. Injections of an miR-125b-5p mimic and LNA inhibitor directly into WAT inhibited and increased beta3-adrenoceptor-mediated induction of UCP1, respectively, and mitochondrial brite adipocyte marker expression and mitochondriogenesis. CONCLUSION: Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression. PMID- 27656400 TI - Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis. AB - OBJECTIVE: Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. METHOD: We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). RESULTS: 2-deoxyglucose, a sympathetic nervous system stimulant, caused beta-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the beta3-AR agonist CL316,243 dose dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. CONCLUSIONS: These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis. PMID- 27656401 TI - Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity. AB - OBJECTIVE: A disturbed day-night rhythm is associated with metabolic perturbations that can lead to obesity and type 2 diabetes mellitus (T2DM). In skeletal muscle, a reduced oxidative capacity is also associated with the development of T2DM. However, whether oxidative capacity in skeletal muscle displays a day-night rhythm in humans has so far not been investigated. METHODS: Lean, healthy subjects were enrolled in a standardized living protocol with regular meals, physical activity and sleep to reflect our everyday lifestyle. Mitochondrial oxidative capacity was examined in skeletal muscle biopsies taken at five time points within a 24-hour period. RESULTS: Core-body temperature was lower during the early night, confirming a normal day-night rhythm. Skeletal muscle oxidative capacity demonstrated a robust day-night rhythm, with a significant time effect in ADP-stimulated respiration (state 3 MO, state 3 MOG and state 3 MOGS, p < 0.05). Respiration was lowest at 1 PM and highest at 11 PM (state 3 MOGS: 80.6 +/- 4.0 vs. 95.8 +/- 4.7 pmol/mg/s). Interestingly, the fluctuation in mitochondrial function was also observed in whole-body energy expenditure, with peak energy expenditure at 11 PM and lowest energy expenditure at 4 AM (p < 0.001). In addition, we demonstrate rhythmicity in mRNA expression of molecular clock genes in human skeletal muscle. CONCLUSIONS: Our results suggest that the biological clock drives robust rhythms in human skeletal muscle oxidative metabolism. It is tempting to speculate that disruption of these rhythms contribute to the deterioration of metabolic health associated with circadian misalignment. PMID- 27656402 TI - mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. AB - OBJECTIVE: We have recently shown that acute inhibition of both mTOR complexes (mTORC1 and mTORC2) increases whole-body lipid utilization, while mTORC1 inhibition had no effect. Therefore, we tested the hypothesis that mTORC2 regulates lipid metabolism in skeletal muscle. METHODS: Body composition, substrate utilization and muscle lipid storage were measured in mice lacking mTORC2 activity in skeletal muscle (specific knockout of RICTOR (Ric mKO)). We further examined the RICTOR/mTORC2-controlled muscle metabolome and proteome; and performed follow-up studies in other genetic mouse models and in cell culture. RESULTS: Ric mKO mice exhibited a greater reliance on fat as an energy substrate, a re-partitioning of lean to fat mass and an increase in intramyocellular triglyceride (IMTG) content, along with increases in several lipid metabolites in muscle. Unbiased proteomics revealed an increase in the expression of the lipid droplet binding protein Perilipin 3 (PLIN3) in muscle from Ric mKO mice. This was associated with increased AMPK activity in Ric mKO muscle. Reducing AMPK kinase activity decreased muscle PLIN3 expression and IMTG content. AMPK agonism, in turn, increased PLIN3 expression in a FoxO1 dependent manner. PLIN3 overexpression was sufficient to increase triglyceride content in muscle cells. CONCLUSIONS: We identified a novel link between mTORC2 and PLIN3, which regulates lipid storage in muscle. While mTORC2 is a negative regulator, we further identified AMPK as a positive regulator of PLIN3, which impacts whole-body substrate utilization and nutrient partitioning. PMID- 27656403 TI - The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512. AB - OBJECTIVE: Insulin release from pancreatic islet beta cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs) by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512) (also known as islet antigen 2/Ptprn). Here we investigated how Ica512 modulates SG trafficking and exocytosis. METHODS: Transcriptomic changes in Ica512 (-/-) mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. RESULTS: The F-actin modifier villin was consistently downregulated in Ica512 (-/-) mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of beta cells and dispersed villin (-/-) islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. CONCLUSION: Our findings show that villin controls the size of the F actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. PMID- 27656404 TI - Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons. AB - OBJECTIVE: The ventromedial hypothalamic nucleus (VMH) regulates energy balance and glucose homeostasis. Leptin and insulin exert metabolic effects via their cognate receptors expressed by the steroidogenic factor 1 (SF1) neurons within the VMH. However, detailed cellular mechanisms involved in the regulation of these neurons by leptin and insulin remain to be identified. METHODS: We utilized genetically-modified mouse models and performed patch-clamp electrophysiology experiments to resolve this issue. RESULTS: We identified distinct populations of leptin-activated and leptin-inhibited SF1 neurons. In contrast, insulin uniformly inhibited SF1 neurons. Notably, we found that leptin-activated, leptin-inhibited, and insulin-inhibited SF1 neurons are distinct subpopulations within the VMH. Leptin depolarization of SF1 neuron also required the PI3K p110beta catalytic subunit. This effect was mediated by the putative transient receptor potential C (TRPC) channel. On the other hand, hyperpolarizing responses of SF1 neurons by leptin and insulin required either of the p110alpha or p110beta catalytic subunits, and were mediated by the putative ATP-sensitive K(+) (KATP) channel. CONCLUSIONS: Our results demonstrate that specific PI3K catalytic subunits are responsible for the acute effects of leptin and insulin on VMH SF1 neurons, and provide insights into the cellular mechanisms of leptin and insulin action on VMH SF1 neurons that regulate energy balance and glucose homeostasis. PMID- 27656406 TI - Fibroblast growth factor 21 has no direct role in regulating fertility in female mice. AB - OBJECTIVE: Reproduction is an energetically expensive process. Insufficient calorie reserves, signaled to the brain through peripheral signals such as leptin, suppress fertility. Recently, fibroblast growth factor 21 (FGF21) was implicated as a signal from the liver to the hypothalamus that directly inhibits the hypothalamic-gonadotropin axis during fasting and starvation. However, FGF21 itself increases metabolic rate and can induce weight loss, which suggests that the effects of FGF21 on fertility may not be direct and may reflect changes in energy balance. METHODS: To address this important question, we evaluated fertility in several mouse models with elevated FGF21 levels including ketogenic diet fed mice, fasted mice, mice treated with exogenous FGF21 and transgenic mice over-expressing FGF21. RESULTS: We find that ketogenic diet fed mice remain fertile despite significant elevation in serum FGF21 levels. Absence of FGF21 does not alter transient infertility induced by fasting. Centrally infused FGF21 does not suppress fertility despite its efficacy in inducing browning of inguinal white adipose tissue. Furthermore, a high fat diet (HFD) can restore fertility of female FGF21-overexpressing mice, a model of growth restriction, even in the presence of supraphysiological serum FGF21 levels. CONCLUSIONS: We conclude that FGF21 is not a direct physiological regulator of fertility in mice. The infertility observed in FGF21 overexpressing mice is likely driven by the increased energy expenditure and consequent excess calorie requirements resulting from high FGF21 levels. PMID- 27656405 TI - Sexually dimorphic brain fatty acid composition in low and high fat diet-fed mice. AB - OBJECTIVE: In this study, we analyzed the fatty acid profile of brains and plasma from male and female mice fed chow or a western-style high fat diet (WD) for 16 weeks to determine if males and females process fatty acids differently. Based on the differences in fatty acids observed in vivo, we performed in vitro experiments on N43 hypothalamic neuronal cells to begin to elucidate how the fatty acid milieu may impact brain inflammation. METHODS: Using a comprehensive mass spectrometry fatty acid analysis, which includes a profile for 52 different fatty acid isomers, we assayed the plasma and brain fatty acid composition of age matched male and female mice maintained on chow or a WD. Additionally, using the same techniques, we determined the fatty acid composition of N43 hypothalamic cells following exposure to palmitic and linoleic acid, alone or in combination. RESULTS: Our data demonstrate there is a sexual dimorphism in brain fatty acid content both following the consumption of the chow diet, as well as the WD, with males having an increased percentage of saturated fatty acids and reductions in omega6-polyunsaturated fatty acids when compared to females. Interestingly, we did not observe a sexual dimorphism in fatty acid content in the plasma of the same mice. Furthermore, exposure of N43 cells to the omega6-PUFA linoleic acid, which is higher in female brains when compared to males, reduces palmitic acid induced inflammation. CONCLUSIONS: Our data suggest male and female brains, and not plasma, differ in their fatty acid profile. This is the first time, to our knowledge, lipidomic analyses has been used to directly test the hypothesis there is a sexual dimorphism in brain and plasma fatty acid composition following consumption of the chow diet, as well as following exposure to the WD. PMID- 27656407 TI - Male-lineage transmission of an acquired metabolic phenotype induced by grand paternal obesity. AB - OBJECTIVE: Parental obesity can induce metabolic phenotypes in offspring independent of the inherited DNA sequence. Here we asked whether such non-genetic acquired metabolic traits can be passed on to a second generation that has never been exposed to obesity, even as germ cells. METHODS: We examined the F1, F2, and F3 a/a offspring derived from F0 matings of obese prediabetic A (vy) /a sires and lean a/a dams. After F0, only lean a/a mice were used for breeding. RESULTS: We found that F1 sons of obese founder males exhibited defects in glucose and lipid metabolism, but only upon a post-weaning dietary challenge. F1 males transmitted these defects to their own male progeny (F2) in the absence of the dietary challenge, but the phenotype was largely attenuated by F3. The sperm of F1 males exhibited changes in the abundance of several small RNA species, including the recently reported diet-responsive tRNA-derived fragments. CONCLUSIONS: These data indicate that induced metabolic phenotypes may be propagated for a generation beyond any direct exposure to an inducing factor. This non-genetic inheritance likely occurs via the actions of sperm noncoding RNA. PMID- 27656408 TI - Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus. AB - OBJECTIVE: The dorsomedial hypothalamus (DMH) has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques. METHODS: We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp. RESULTS: Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN), where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake. CONCLUSION: DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN. PMID- 27656409 TI - The role of autonomic efferents and uncoupling protein 1 in the glucose-lowering effect of leptin therapy. AB - OBJECTIVE: Leptin reverses hyperglycemia in rodent models of type 1 diabetes (T1D). Direct application of leptin to the brain can lower blood glucose in diabetic rodents, and can activate autonomic efferents and non-shivering thermogenesis in brown adipose tissue (BAT). We investigated whether leptin reverses hyperglycemia through a mechanism that requires autonomic innervation, or uncoupling protein 1 (UCP1)-mediated thermogenesis. METHODS: To examine the role of parasympathetic and sympathetic efferents in the glucose-lowering action of leptin, mice with a subdiaphragmatic vagotomy or 6-hydroxydopamine induced chemical sympathectomy were injected with streptozotocin (STZ) to induce hyperglycemia, and subsequently leptin treated. To test whether the glucose lowering action of leptin requires activation of UCP1-mediated thermogenesis in BAT, we administered leptin in STZ-diabetic Ucp1 knockout (Ucp1 (-/-)) mice and wildtype controls. RESULTS: Leptin ameliorated STZ-induced hyperglycemia in both intact and vagotomised mice. Similarly, mice with a partial chemical sympathectomy did not have an attenuated response to leptin-mediated glucose lowering relative to sham controls, and showed intact leptin-induced Ucp1 expression in BAT. Although leptin activated BAT thermogenesis in STZ-diabetic mice, the anti-diabetic effect of leptin was not blunted in Ucp1 (-/-) mice. CONCLUSIONS: These results suggest that leptin lowers blood glucose in insulin deficient diabetes through a manner that does not require parasympathetic or sympathetic innervation, and thus imply that leptin lowers blood glucose through an alternative CNS-mediated mechanism or redundant target tissues. Furthermore, we conclude that the glucose lowering action of leptin is independent of UCP1 dependent thermogenesis. PMID- 27656410 TI - Microbially produced glucagon-like peptide 1 improves glucose tolerance in mice. AB - OBJECTIVE: The enteroendocrine hormone glucagon-like peptide 1 (GLP-1) is an attractive anti-diabetic therapy. Here, we generated a recombinant Lactococcus lactis strain genetically modified to produce GLP-1 and investigated its ability to improve glucose tolerance in mice on chow or high-fat diet (HFD). METHODS: We transformed L. lactis FI5876 with either empty vector (pUK200) or murine GLP-1 expression vector to generate LL-UK200 and LL-GLP1, respectively, and determined their potential to induce insulin secretion by incubating primary islets from wild-type (WT) and GLP-1 receptor knockout (GLP1R-KO) mice with culture supernatant of these strains. In addition, we administered these strains to mice on chow or HFD. At the end of the study period, we measured plasma GLP-1 levels, performed intraperitoneal glucose tolerance and insulin tolerance tests, and determined hepatic expression of the gluconeogenic genes G6pc and Pepck. RESULTS: Insulin release from primary islets of WT but not GLP1R-KO mice was higher following incubation with culture supernatant from LL-GLP1 compared with LL UK200. In mice on chow, supplementation with LL-GLP1 versus LL-UK200 promoted increased vena porta levels of GLP-1 in both WT and GLP1R-KO mice; however, LL GLP1 promoted improved glucose tolerance in WT but not in GLP1R-KO mice, indicating a requirement for the GLP-1 receptor. In mice on HFD and thus with impaired glucose tolerance, supplementation with LL-GLP1 versus LL-UK200 promoted a pronounced improvement in glucose tolerance together with increased insulin levels. Supplementation with LL-GLP1 versus LL-UK200 did not affect insulin tolerance but resulted in reduced expression of G6pc in both chow and HFD-fed mice. CONCLUSIONS: The L. lactis strain genetically modified to produce GLP-1 is capable of stimulating insulin secretion from islets and improving glucose tolerance in mice. PMID- 27656412 TI - Involvement of CD147 on multidrug resistance through the regulation of P glycoprotein expression in K562/ADR leukemic cell line. AB - The relationship between P-gp and CD147 in the regulation of MDR in leukemic cells has not been reported. This study aimed to investigate the correlation between CD147 and P-gp in the regulation of drug resistance in the K562/ADR leukemic cell line. The results showed that drug-resistant K562/ADR cells expressed significantly higher P-gp and CD147 levels than drug-free K562/ADR cells. To determine the regulatory effect of CD147 on P-gp expression, anti-CD147 antibody MEM-M6/6 significantly decreased P-gp and CD147 mRNA and protein levels. This is the first report to show that CD147 mediates MDR in leukemia through the regulation of P-gp expression. PMID- 27656413 TI - Transcriptional profiling of the effect of lipopolysaccharide (LPS) pretreatment in blood from probiotics-treated dairy cows. AB - Probiotic supplements are beneficial for animal health and rumen function; and lipopolysaccharides (LPS) from gram negative bacteria have been associated with inflammatory diseases. In this study the transcriptional profile in whole blood collected from probiotics-treated cows was investigated in response to stimulation with lipopolysaccharides (LPS) in vitro. Microarray experiment was performed between LPS-treated and control samples using the Agilent one-color bovine v2 bovine (v2) 4x44K array slides. Global gene expression analysis identified 13,658 differentially expressed genes (fold change cutoff >= 2, P < 0.05), 3816 upregulated genes and 9842 downregulated genes in blood in response to LPS. Treatment with LPS resulted in increased expression of TLR4 (Fold change (FC) = 3.16) and transcription factor NFkB (FC = 5.4) and decreased the expression of genes including TLR1 (FC = - 2.54), TLR3 (FC = - 2.43), TLR10 (FC = - 3.88), NOD2 (FC = - 2.4), NOD1 (FC = - 2.45) and pro-inflammatory cytokine IL1B (- 3.27). The regulation of the genes involved in inflammation signaling pathway suggests that probiotics may stimulate the innate immune response of animal against parasitic and bacterial infections. We have provided a detailed description of the experimental design, microarray experiment and normalization and analysis of data which have been deposited into NCBI Gene Expression Omnibus (GEO): GSE75240. PMID- 27656411 TI - Glucagon receptor gene deletion in insulin knockout mice modestly reduces blood glucose and ketones but does not promote survival. AB - OBJECTIVE: It has been thought that the depletion of insulin is responsible for the catabolic consequences of diabetes; however, evidence suggests that glucagon also plays a role in diabetes pathogenesis. Glucagon suppression by glucagon receptor (Gcgr) gene deletion, glucagon immunoneutralization, or Gcgr antagonist can reverse or prevent type 1 diabetes in rodents suggesting that dysregulated glucagon is also required for development of diabetic symptoms. However, the models used in these studies were rendered diabetic by chemical- or immune mediated beta-cell destruction, in which insulin depletion is incomplete. Therefore, it is unclear whether glucagon suppression could overcome the consequence of the complete lack of insulin. METHODS: To directly test this we characterized mice that lack the Gcgr and both insulin genes (GcgrKO/InsKO). RESULTS: In both P1 pups and mice that were kept alive to young adulthood using insulin therapy, blood glucose and plasma ketones were modestly normalized; however, mice survived for only up to 6 days, similar to GcgrHet/InsKO controls. In addition, Gcgr gene deletion was unable to normalize plasma leptin levels, triglycerides, fatty acids, or hepatic cholesterol accumulation compared to GcgrHet/InsKO controls. CONCLUSION: Therefore, the metabolic manifestations associated with a complete lack of insulin cannot be overcome by glucagon receptor gene inactivation. PMID- 27656414 TI - Fine resolution mapping of double-strand break sites for human ribosomal DNA units. AB - DNA breakage arises during a variety of biological processes, including transcription, replication and genome rearrangements. In the context of disease, extensive fragmentation of DNA has been described in cancer cells and during early stages of neurodegeneration (Stephens et al., 2011 Stephens et al. (2011) [5]; Blondet et al., 2001 Blondet et al. (2001) [1]). Stults et al. (2009) Stults et al. (2009) [6] reported that human rDNA gene clusters are hotspots for recombination and that rDNA restructuring is among the most common chromosomal alterations in adult solid tumours. As such, analysis of rDNA regions is likely to have significant prognostic and predictive value, clinically. Tchurikov et al. (2015a, 2016) Tchurikov et al. (2015a, 2016) [7], [9] have made major advances in this direction, reporting that sites of human genome double-strand breaks (DSBs) occur frequently at sites in rDNA that are tightly linked with active transcription - the authors used a RAFT (rapid amplification of forum termini) protocol that selects for blunt-ended sites. They reported the relative frequency of these rDNA DSBs within defined co-ordinate 'windows' of varying size and made these data (as well as the relevant 'raw' sequencing information) available to the public (Tchurikov et al., 2015b). Assay designs targeting rDNA DSB hotspots will benefit greatly from the publication of break sites at greater resolution. Here, we re-analyse public RAFT data and make available rDNA DSB co-ordinates to the single-nucleotide level. PMID- 27656415 TI - Mitochondrial m.3243A > G mutation and carotid artery dissection. AB - The common m.3243A > G mutation of the mitochondrial DNA tRNALeu (UUR) gene is a maternally inherited mutation causing a wide spectrum of neurological and multisystemic disorders, including MELAS, characterized by recurrent cerebral infarction from young age. Vascular pathology in mitochondrial diseases has been described for small vessels, while large vessels involvement in mitochondrial diseases is considered rare. Here we report two female patients harboring the m.3243A > G mutation, in whom the diagnosis of mitochondrial disease was made after acute dissection of the internal carotid arteries. Our cases expand the clinical spectrum of this mutation, and support the idea of large vessels vasculopathy due to impaired mitochondrial function in the vessel wall that may lead to arterial wall weakness. Thus, stroke in mitochondrial diseases could also be related to large vessels disease, but further studies are strongly needed. Moreover, mitochondrial aetiology should be kept in mind in patients with large vessel dissection, especially in those with additional mitochondrial red flags. PMID- 27656416 TI - Angiomyomatous Leiomyoma of a Female Urethral Meatus Recurrence After Seven Years of the Resection: A Case Report. AB - A 20 years old woman had an external urethral orifice mass and received an excision operation. Seven years later, she complained a tumor with pain that was similar to the previous tumor. She underwent the tumor removal. Pathological diagnosis was a urethral angiomyomatous leiomyoma in the new concept of estrogen receptor-positive smooth muscle tumors. PMID- 27656417 TI - Urothelial Carcinoma Recurrence at an Ileal Orthotopic Neobladder and Unilateral Lower Ureter After Surgery. AB - The recurrence of urothelial carcinoma in an orthotopic neobladder is rare. We report the case of a 61-year-old man with a muscle-invasive bladder tumor that was treated using radical cystectomy and the creation of a Studer's orthotopic neobladder. However, nine years after the cystectomy, we detected a mass at the left ureteroileal anastomosis. We successfully performed Studer's neobladder resection, urethrectomy, and left nephroureterectomy to remove the entire mass. Pathological examination revealed urothelial carcinoma with adenocarcinoma in the neobladder and adenocarcinomatous metastasis in the mesenteric lymph node. PMID- 27656418 TI - Extraperitoneal Rupture of a Bladder Diverticulum and the Role of Multidetector Computed Tomography Cystography. AB - Nontraumatic rupture of the bladder is less widely recognized than traumatic rupture, with a challenging early diagnosis due to high variability in clinical presentations. We report a case of extraperitoneal rupture of a bladder diverticulum in a patient with diabetes mellitus who presented with paralytic ileus. Despite conservative management, the patient developed sepsis requiring surgical treatment. Urinary tract infection and bladder outlet obstruction were considered to be potential mechanisms of the rupture. Multidetector computed tomography cystography should be used as the first-line modality when evaluating for a suspected bladder rupture, even in patients with nontraumatic bladder rupture. PMID- 27656419 TI - Actionable Intelligence Provided by Pancreatic Cancer Genomic Landscape: Are Targets for Curative Therapy On The Map? PMID- 27656420 TI - The Impact of L-Dex((r)) Measurements in Assessing Breast Cancer-Related Lymphedema as Part of Routine Clinical Practice. AB - PURPOSE: With improved survivorship, the prevalence of breast cancer-related lymphedema (BCRL) continues to increase, leading to impairment of a patients' quality of life. While traditional diagnostic methods are limited by an inability to detect BCRL until clinically apparent, bioimpedance spectroscopy (BIS) has been shown to detect subclinical BCRL. The purpose of this study is to evaluate the role of BIS in the early detection of BCRL, as well as assessment of response to BCRL treatment. METHODS: A retrospective review of 1,133 patients treated between November 2008 and July 2013 at two surgical practices was performed. Eligible patients (n = 326) underwent preoperative and postoperative L-Dex measurements. Patients were identified as having subclinical lymphedema if they were asymptomatic and the L-Dex score increased >10 U above baseline and were monitored following treatment. Patients were stratified by lymph node dissection technique [sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND)] and receipt of BCRL treatment. RESULTS: The average age of the cohort was 56.2 years old, and mean follow-up was 21.7 months. Of the 326 patients, 210 underwent SLNB and 116 underwent ALND. BCRL was identified by L-Dex in 40 patients (12.3%). The cumulative incidence rate of subclinical lymphedema was 4.3% for SLNB (n = 9) and 26.7% for ALND (n = 31). Of those diagnosed with BCRL, 50% resolved following treatment, 27.5% underwent treatment without resolution, and 22.5% had resolution without treatment. The prevalence of persistent, clinical BCRL was 0.5% for SLNB and 8.6% for ALND. CONCLUSION: This study demonstrates both the feasibility and clinical utility of implementing L-Dex measurements in routine breast cancer care. L-Dex identified patients with possible subclinical BCRL and allowed for assessment of response to therapy. PMID- 27656423 TI - Histological and Histopathological Study of Incus. AB - INTRODUCTION: Chronic otits media is long standing infection of middle ear cleft which commonly involves bone erosion. Bone destruction seen in unsafe chronic otitis media mainly involves the ossicles, incus being frequently involved ossicle. So, an investigation of the histopathological changes in incus was carried out to report the various histopathological changes occurring in chronic otitis media. AIM: Aim of the study is to report the structural changes occuring in incus bone in chronic otitis media. MATERIALS AND METHODS: Ten normal incuses and ten pathological incuses which were removed during the surgery for chronic otitis media (both with and without cholesteotoma) were studied histologically, after staining with haematoxylin and eosin. RESULTS: Normal incus showed compact bone pattern of concentric rings, like that of any long bone of body. Pathological incuses of chronic otitis media (both with and without cholestoetoma) showed similar changes, i.e., stratified squamous epithelium, with distorted concentric rings and increased osseous spaces. CONCLUSION: The study was undertaken, so that the knowledge to histological changes may help the clinicians to take more rational decisions regarding their diagnosis and therapeutic interventions to prevent the changes occurring in the bone in chronic otitis media. PMID- 27656421 TI - The Place of FDG PET/CT in Renal Cell Carcinoma: Value and Limitations. AB - Unlike for most other malignancies, application of FDG PET/CT is limited for renal cell carcinoma (RCC), mainly due to physiological excretion of 18F-fluoro-2 deoxy-2-d-glucose (FDG) from the kidneys, which decreases contrast between renal lesions and normal tissue, and may obscure or mask the lesions of the kidneys. Published clinical observations were discordant regarding the role of FDG PET/CT in diagnosing and staging RCC, and FDG PET/CT is not recommended for this purpose based on current national and international guidelines. However, quantitative FDG PET/CT imaging may facilitate the prediction of the degree of tumor differentiation and allows for prognosis of the disease. FDG PET/CT has potency as an imaging biomarker to provide useful information about patient's survival. FDG PET/CT can be effectively used for postoperative surveillance and restaging with high sensitivity, specificity, and accuracy, as early diagnosis of recurrent/metastatic disease can drastically affect therapeutic decision and alter outcome of patients. FDG uptake is helpful for differentiating benign or bland emboli from tumor thrombosis in RCC patients. FDG PET/CT also has higher sensitivity and accuracy when compared with bone scan to detect RCC metastasis to the bone. FDG PET/CT can play a strong clinical role in the management of recurrent and metastatic RCC. In monitoring the efficacy of new target therapy such as tyrosine kinase inhibitors (TKIs) treatment for advanced RCC, FDG PET/CT has been increasingly used to assess the therapeutic efficacy, and change in FDG uptake is a strong indicator of biological response to TKI. PMID- 27656422 TI - The Challenges of Detecting Circulating Tumor Cells in Sarcoma. AB - Sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin, many of which have a propensity to develop distant metastases. Cancer cells that have escaped from the primary tumor are able to invade into surrounding tissues, to intravasate into the bloodstream to become circulating tumor cells (CTCs), and are responsible for the generation of distant metastases. Due to the rarity of these tumors and the absence of specific markers expressed by sarcoma tumor cells, the characterization of sarcoma CTCs has to date been relatively limited. Current techniques for isolating sarcoma CTCs are based on size criteria, the identification of circulating cells that express either common mesenchymal markers, sarcoma-specific markers, such as CD99, CD81, or PAX3, and chromosomal translocations found in certain sarcoma subtypes, such as EWS-FLI1 in Ewing's sarcoma, detection of osteoblast-related genes, or measurement of the activity of specific metabolic enzymes. Further studies are needed to improve the isolation and characterization of sarcoma CTCs, to demonstrate their clinical significance as predictive and/or prognostic biomarkers, and to utilize CTCs as a tool for investigating the metastatic process in sarcoma and to identify novel therapeutic targets. The present review provides a short overview of the most recent literature on CTCs in sarcoma. PMID- 27656424 TI - A South Indian Cadaveric Study About the Relationship of Hepatic Segment of Inferior Vena Cava with the Liver. AB - INTRODUCTION: Inferior Vena Cava (IVC) is the largest vein of the body. It runs vertically upwards in the abdomen, behind the liver. Its course is very constant in relation to liver. However, the amount of liver parenchyma related to it can vary from person to person. The data regarding its course and relations may be very useful to radiologists and surgeons during surgical treatment procedures for Budd-Chiari syndrome, liver carcinoma, liver transplant, venous cannulations and many other clinical procedures. AIM: Aim of this study was to document the incidence of straight and curved course of IVC in relation to liver and also to note the pattern in which the liver tissue was related to the IVC. MATERIALS AND METHODS: In the current study, 95 adult cadaveric livers were observed; specifically to study the course/direction of the hepatic segment of IVC in relation to the liver. The extent of liver tissue related to various aspects of IVC was also studied. The course of the IVC was classified as straight and curved; and the relationship of liver parenchyma to the IVC was classified into 6 categories. The data was expressed as percentage incidence. RESULTS: In 78.94% cases, the IVC had a straight course in relation to the liver; whereas in 21.06% cases, it had a left sided curve (concavity of the curve towards the caudate lobe) in its course. In 6.31% cases, IVC travelled in a tunnel, being encircled by the liver parenchyma all around; in 36.84% cases, it was covered by liver parenchyma on front and sides so that only posterior surface of IVC was visible; in 3.15% cases it was covered by liver tissue on front, sides and also partly on posterior aspect; in 50.52% of cases, its anterior surface, sides and left edge of the posterior surface was covered by liver tissue; and in 3.15% cases it was covered only from the front by the liver tissue. CONCLUSION: The data being reported here might be useful for surgeons while planning and executing various hepatic surgeries and also to the radiologists in planning and performing venous cannulation and therapeutic procedures. Since in many livers, the curvature of IVC was associated with enlarged caudate lobe, the curved IVC could hint about the increase in the volume of caudate lobe or liver itself. PMID- 27656425 TI - Abnormal Nuclear Variations in Response to Radiotherapy- As a Tool in Treatment Planning and Assessment of Prognosis. AB - INTRODUCTION: The treatment approaches for oral squamous cell carcinoma (OSCC) include single management with surgery, radiotherapy, along with chemotherapy or various combinations of these modalities. The estimation of radio sensitivity of individual tumours is essential for planning the optimum radiation schedule for each patient. Assessment of radiation induced histo morphological changes in the nucleus is a known marker of radiosensitivity. AIM: The aim of this study was to establish the relationship between nuclear changes with radiation dose and to investigate the prospect of utilizing them as an assay to predict tumour response to radiotherapy in oral cancers. MATERIALS AND METHODS: The present study included 50 patients (age range of 30-65yrs) with histopathologically confirmed squamous cell carcinoma of oral mucosa and being treated by radiotherapy alone with a radiation dose schedule of 4, 14, 24 and 60 Gy respectively at 2(nd), 7(th), 12(th) and 30(th) day. From the included patients, smear of the buccal mucosa was collected and was air dried and fixed with methanol. The Nuclear changes of Micronucleus (MN), Nuclear Budding (NB) and Multinucleation (MNU) were evaluated under the bright field microscopy after staining with Giemsa and May Grunwald's stain. RESULTS: Out of the 50, 37(74%) were males and 13(26%) were females (Ratio 3:1). The mean percentage increase of MN and MNU were found to be statistically significant (p=0.001) when compared with pre-treatment day. Similar findings were seen with NB, except between pretreatment and after 14 Gy (p 0.110). In the present study the measurement of relative increment index done in respect to all nuclear abnormalities show a sustained increase with increasing dosage of radiation. CONCLUSION: The present study, was undertaken to explore the possibility of establishing a relationship between the frequencies of nuclear abnormalities in patients with oral cancer with applied dosage and duration of radiotherapy. The progressive increase in Micronucleus and Multinucleation indices with increasing dose of radiation proves that these parameters can be used as indicators for assessing the response of tumour for radiotherapy. These parameters can be used as prognostic indicator in oral carcinoma cases undergoing radiotherapy. PMID- 27656426 TI - Multiple Heads of Gastrocnemius with Bipennate Fiber Arrangement- A Clinically Significant Variation. AB - It is common to have additional muscles or muscle slips in the extremities. Some of them may compress the nerves and vessels or restrict the movements, while others may enhance the muscular activity. However, a small number of them may go unnoticed. Knowledge of such variant muscles becomes important for plastic surgeons while performing various reconstructive surgeries and for clinicians while managing the pain. A case of multiple heads of gastrocnemius muscle was observed during routine dissection of the right lower limb of about 70-year-old male cadaver. It was observed that the medial head of gastrocnemius was attached to the femur with 3 thick heads and lateral head was arising from the lateral condyle of femur by 3 thick heads. All the heads of the muscles remained separate till they formed tendocalcaneus. Some of these heads showed bipinnate fiber arrangement. All the heads were innervated by the branches of tibial nerve. As the muscle heads passed down from their origin, they entrapped the sural nerve and sural nerve was seen emerging at the beginning of tendocalcaneus. Further, detailed literature and the clinical and surgical importance of the case are discussed. PMID- 27656427 TI - Effects of Long Term Exposure of 900-1800 MHz Radiation Emitted from 2G Mobile Phone on Mice Hippocampus- A Histomorphometric Study. AB - INTRODUCTION: The advancement in the telecommunications technology with multi functional added features in mobile phone, attracts more users of all age group. It is alarming to note that, the mobile phone use has increased amongst children and they are exposed to potentially harmful radiofrequency radiation in their lifetime. AIM: To investigate the long term exposure of 900 to 1800 MHz radiations emitted from 2G mobile phone in mice hippocampus at histomorphometric level. MATERIALS AND METHODS: With due approval from institutional animal ethics committee, 36 mice were exposed to 2G mobile phone radiation, 48 minutes per day for a period of 30-180 days. The control group was kept under similar conditions without 2G exposure. Mice were sacrificed and the brain was removed from the first month to six months period. Brain was removed from the cranial cavity and hippocampus region was dissected out carefully and processed for routine histological study. Random serial sections were analysed under microscope for histomorphometric changes. For statistical analysis, independent t-test was used for comparing control and 2G exposed groups. RESULTS: The mean density of neurons in the hippocampus regions CA1, CA2 and DGDB from first to sixth month was significantly lower in the 2G exposed groups; however, in CA3 and DGVB, the 2G exposed mice showed significantly higher density of neurons. The mean nuclear diameter of neurons in the hippocampus region of CA1, CA2, CA3, DGDB and DGVB from first to sixth months showed lower nuclear diameter in 2G exposed mice. CONCLUSION: The long term exposure to 900-1800 MHz frequency radiations emitted from 2G mobile phone could cause significantly reduced neuron density and decreased nuclear diameter in the hippocampus neurons of mice. PMID- 27656428 TI - Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats. AB - INTRODUCTION: Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. AIM: To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. MATERIALS AND METHODS: Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. RESULTS: Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. CONCLUSION: Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels. PMID- 27656429 TI - Analysis of Arterial Blood Gas Report in Chronic Kidney Diseases - Comparison between Bedside and Multistep Systematic Method. AB - INTRODUCTION: Acid Base Disorders (ABDs) are commonly encountered in critically ill Chronic Kidney Disease (CKD) patients. Timely and correct analysis of Arterial Blood Gases (ABG) is critical for the diagnosis, treatment and prediction of outcome of the patients. AIM: The aim was to explore type and prevalence of ABDs in 31 critically ill CKD patients from a tertiary care hospital in Maharashtra, to compare two methods of analysis- bedside and systematic approaches and to clinically correlate the nature of ABDs in these patients. MATERIALS AND METHODS: The initial ABG reports of 31 consecutive CKD patients were analysed by two methods. Medica Easy stat analyser was the equipment for analysis with Principle of potentiometry and ion selective electrode for pH and pCO2 and amperometry for pO2. Serum albumin was also measured by Bromocresol green dye binding method using liquixx albumin kit in Erba XL 300 autoanalyser. STATISTICAL ANALYSIS: Chi-square test was used for statistical analysis using Epi Info version 3.5.4 and SPSS 14.0 softwares. RESULTS: The systematic method showed a significantly higher prevalence of mixed disorders (50%) compared to bedside method (12.9%). Most prevalent disorder by bedside method was metabolic acidosis in 15 cases (48.39%). By the systematic method, 3 reports were invalid. As a single category, most prevalent type was both simple respiratory alkalosis and mixed metabolic acidosis with respiratory alkalosis- 6 of 31 cases in each type (19.36% each). As a whole, metabolic acidosis (including both High Anion Gap Metabolic Acidosis or HAGMA and Non Anion Gap Metabolic Acidosis or NAGMA with 4 in each type) was most prevalent- 8 of 31(25.8%). CONCLUSION: Systematic approach was more effective in diagnosing mixed acid base disorders. By systematic method the findings of analysis in most cases could be correlated with the clinical condition and provisional diagnosis. Thus interpretation of ABDs by using stepwise approach could be useful to the clinicians in early diagnosis and management of the patients. PMID- 27656431 TI - Plasma Myeloperoxidase and Total Sialic Acid as Prognostic Indicators in Acute Coronary Syndrome. AB - INTRODUCTION: Acute Coronary Syndrome (ACS) is the leading cause of death worldwide. Oxidative stress and inflammation play important role in the destabilization of plaques leading to ACS. Markers which reflect this pathophysiologic mechanism may have prognostic value. Myeloperoxidase (MPO) and Sialic acid are markers of inflammation and oxidative stress. Both these markers are increased in patients with ACS. Their prognostic value in ACS is not well established. AIM: To analyse the prognostic value of plasma myeloperoxidase and total sialic acid levels in patients with suspected acute coronary syndrome. MATERIALS AND METHODS: A prospective study was conducted on 93 consecutively admitted patients with chest pain from July 2011 to September 2011. Plasma MPO and total sialic acid levels on admission were estimated spectrophotometrically. These were compared with extent of disease, development of complications during the hospital stay, left ventricular ejection fraction and mean duration of stay in hospital. RESULTS: Plasma MPO and total sialic acid levels were significantly higher in patients with myocardial infarction than those with unstable and stable angina (p<0.001 and p<0.007 respectively). The levels of plasma MPO and sialic acid levels were significantly higher in patients who developed complications like heart failure, arrhythmias, renal failure during their stay in hospital (p<0.011 and p<0.006 respectively). Ejection fraction was significantly low in patients with high MPO levels (p<0.011). CONCLUSION: In patients with ACS, plasma MPO and total sialic acid levels on admission could predict the development of complications during their hospital stay. MPO levels correlated with ejection fraction in patients with ACS. PMID- 27656430 TI - Association of Salivary Osteopontin Levels with Glycaemic Status and Microalbuminuria - in Patients with Type 2 Diabetes Mellitus. AB - INTRODUCTION: The monitoring of glycaemic status in patients with T2DM is mainly through blood tests (Fasting plasma glucose and HbA1c), which are invasive and involves painful pricks. This leads to poor patient compliance and soon could lead to various micro and macro vascular complications, which hamper the quality of life. There are no sensitive and specific markers to predict these complications at the earliest. Sialochemistry has recently gained attention for monitoring chronic diseases. Osteopontin is a phospho-glycoprotein molecule, elevated in many inflammatory conditions. AIM: The aim of the study was to evaluate the role of serum and salivary osteopontin in Type 2 Diabetes mellitus (T2DM). MATERIALS AND METHODS: In this case-control study, we recruited 33 cases of T2DM and 31 age and gender matched healthy controls. Body Mass Index (BMI), Waist/Hip Ratio (WHR), Waist Circumference (WC) and blood pressure was recorded. Fasting Plasma Glucose (FPG), salivary glucose, HbA1c, microalbuminuria, systolic BP, serum and salivary osteopontin levels were estimated. RESULTS: FPG, salivary glucose, HbA1c, microalbuminuria, systolic BP, BMI, waist / hip ratio serum and salivary osteopontin levels were significantly high in T2DM cases compared to control subjects. Serum and salivary osteopontin levels were significantly correlated with HbA1c and microalbuminuria in T2DM cases. CONCLUSION: Serum and salivary osteopontin levels are significantly elevated in subjects with T2DM and are associated with glycaemic control and microalbuminuria. PMID- 27656432 TI - Significance of Total Protein, Albumin, Globulin, Serum Effusion Albumin Gradient and LDH in the Differential Diagnosis of Pleural Effusion Secondary to Tuberculosis and Cancer. AB - INTRODUCTION: Lung cancer and Pulmonary tuberculosis are two major public health problems associated with significant morbidity and mortality worldwide particularly in low and middle income countries like India. Wrong diagnosis of lung cancer cases as pulmonary tuberculosis in primary health care system delays the onset of anti-cancer chemotherapy as well as initiation of DOTS thus increasing complication and mortality rate in malignancy patients. In this context easy, cost effective diagnostic tool at primary level must be the priority and need of hour. AIM: To study and evaluate any significance of biochemical parameters (total protein, albumin, globulin, serum effusion albumin gradient, LDH) in serum and pleural effusion secondary to tuberculosis and lung cancer. MATERIALS AND METHODS: A case control study was carried out on patients attending OPD and IPD, Department of Pulmonary Medicine, RMCH. Hundred cases of Tuberculosis effusion, 50 cases of Malignant effusion and 100 age and sex matched apparently healthy controls were taken for correlation of biochemical parameters (total protein, albumin, globulin, serum effusion albumin gradient, LDH) and statistically evaluated to find any significance between tuberculosis, lung cancer and control group. Blood and pleural fluid samples were collected and then subjected to assessment of parameters (total protein, albumin, LDH) by using EM360 Autoanalyser and kits were supplied by Transasia diagnostics. Globulin and Serum Effusion Albumin Gradient (SEAG) was calculated mathematically. STATISTICAL ANALYSIS: Data is presented as mean +/- SD. Comparison of serum and pleural fluid levels (of taken parameters) were done in TB, Lung Cancer and Control groups by ANOVA and students t-test. The p-value <0.05 were considered as statistically significant. RESULTS: We found serum-total protein, albumin, globulin to be significantly higher in TB group than lung cancer group but serum LDH was higher in lung cancer group (in all parameters p=<0.0001). Pleural Fluid-total protein, albumin, globulin was again significantly higher in TB group than lung cancer group and LDH was higher in lung cancer group (p=<0.0001). SEAG is also significantly higher in TB group than lung cancer group (p=<0.002). CONCLUSION: The results suggests early quantization of these parameters can differentiate pulmonary tuberculosis from lung cancer and thus can decrease the mortality rate of lung cancer cases though more extensive study with increased sample size may provide more insights. PMID- 27656433 TI - Biochemical and Clinical Profile in Type 2 Diabetics with Depression. AB - INTRODUCTION: There were 72 million adults with Diabetes Mellitus (DM) in 2013 in the South East Asian region of which India is a part. This figure is expected to rise to more than 123 million by 2035. Some studies have also shown that there is an increased risk of depression in subjects with Type 2 Diabetes Mellitus (T2DM). The present study is an attempt to decipher whether there is any difference in the metabolic and clinical profile between patients having T2DM with depression and without depression. AIM: To study the clinical and biochemical profile of subjects with T2DM and depression and compare a non-depressed diabetic cohort on the same parameters. MATERIALS AND METHODS: The cross-sectional study was conducted at a tertiary care teaching hospital in rural Andhra Pradesh. Patients with T2DM who fulfilled the inclusion and exclusion criteria and attending the outpatient clinic of the General Medicine department were the subjects of this study. The subjects with T2DM were categorized as depressed or non-depressed after administering the Patient Health Questionnare-9. Out of them 30 subjects with depression and 30 without depression were selected. Samples for blood were collected and analysed for glucose, urea, creatinine, lipid profile and glycated haemoglobin. Urine micro protein was estimated. Anthropometric measurements, blood pressure and chronic complications were recorded. RESULTS: The two groups were similar on most of the socio-demographic parameters, biochemical and many of the clinical parameters like age, waist circumference, glycated haemoglobin, lipid profile and insulin use. The Chi-square test for association between the categorical variables like use of insulin, gender predilection, exercise and complications with depression were not significant. CONCLUSION: The study did not show any significant difference between the two groups in terms of the biochemical and clinical profile. PMID- 27656435 TI - Galactomannan Assay and Invasive Pulmonary Aspergillosis - Comparison of the Test Performance at an in-house and the Kit Cut-off. AB - INTRODUCTION: Invasive Pulmonary Aspergillosis (IPA) is an important opportunistic infection with a high degree of mortality and morbidity. Galactomannan assay (GM assay) is found to be useful for diagnosis of IPA in patients with neutropenia. However the utility of this assay has not been evaluated in a mixed patient population with other co-morbid conditions. Though a kit cut-off of 0.5 has been recommended for the diagnosis of IPA, studies have reported a higher sensitivity with cut-offs more than 0.5. AIM: To establish an in-house cut-off and compare its utility with the kit cut-off to diagnose and categorize IPA as proven, probable and possible in patients with varied underlying risk factors. MATERIALS AND METHODS: This observational study was done in St John's Medical College, Bangalore, Karnataka, India from January 2013 December 2014. GM assay was performed on 25 each of healthy controls and clinically diagnosed cases of IPA. The in-house cut-off was calculated by plotting the Receiver Operating Characteristic Curve (ROC). RESULTS: The in-house cut-off was calculated to be 0.52. Using this and the kit cut-off (0.5), the Sensitivity, Specificity, Positive Predictive Value (PPV) and the Negative Predictive Value (NPV) were found to be 75%, 79%, 76%, 82% and 79%, 71%, 77%, 82% respectively. Diabetes mellitus was found to be associated with more than 50% of the patients. CONCLUSION: The established in house cut-off using healthy controls and patients with clinical diagnosis of IPA was not significantly different from that of the kit cut-off. Using either of these cut-offs, we could re-categorize two of the possible IPA cases in the probable group. This study helped to understand the clinical utility of this assay even in a mixed patient population with multiple co-morbidities. PMID- 27656434 TI - Differentiation of Overweight from Normal Weight Young Adults by Postprandial Heart Rate Variability and Systolic Blood Pressure. AB - INTRODUCTION: Obesity and cardiovascular disease are inextricably linked and the health community's response to the current epidemic of adolescent obesity may be improved by the ability to target adolescents at highest risk for developing cardiovascular disease in the future. Overweight manifests early as autonomic dysregulation and current methods do not permit differentiation of overweight adolescents or young adults at highest risk for developing cardiovascular disease. AIM: This study was designed to test the hypothesis that scaling exponents motivated by nonlinear fractal analyses of Heart Rate Variability (HRV) differentiate overweight, otherwise healthy adolescent/young adult subjects at risk for developing prehypertension, the primary forerunner of cardiovascular disease. MATERIALS AND METHODS: The subjects were 18-20year old males with Body Mass Index (BMI) 20.1-42.5kg/m(2). Electrocardiographic inter-beat (RR) intervals were measured during 3h periods of bed rest after overnight fasting and ingestion of 900Cal high-carbohydrate and high-fat test beverages on separate days. Detrended Fluctuation Analysis (DFA), k-means cluster and ANOVA analyses of scaling coefficients alpha, alpha(1), and alpha(2), showed dependencies on hourly measurements of systolic blood pressure and on premeasured BMI. RESULTS: It was observed that alpha value increased during the caloric challenge, appears to represent metabolically-induced changes in HRV across the participants. An ancillary analysis was performed to determine the dependency on BMI without BMI as a parameter. Cluster analysis of the high-carbohydrate test beverage treatment and the high-fat treatment produced grouping with very little overlap. ANOVA on both clusters demonstrated significance at p<0.001. We were able to demonstrate increased sympathetic modulation of our study group during ingestion and metabolism of isocaloric high-carbohydrate and high-fat test beverages. CONCLUSION: These findings demonstrate significantly different clustering of alpha, alpha1, and alpha2 and Systolic Blood Pressure (SBP) with respect to normal, overweight and obese BMI. PMID- 27656436 TI - Indirect Haemagglutination Test in Comparison with ELISA for Detection of Antibodies against Invasive Amoebiasis. AB - INTRODUCTION: Diagnosis of amoebiasis is based on combination of tests like microscopy, imaging, serology and molecular methods. In absence of molecular techniques, serology can be used as an alternative aid. Various serological techniques were reported with different sensitivity and specificity. The diagnostic efficiency of these assays mainly depends on the characteristics of antigen that is being used and various conditions of performance. AIM: To evaluate the efficiency of recombinant calcium binding domain containing protein by Indirect Haemagglutination Assay (IHA) against a commercial ELISA among amoebic liver abscess cases and control group. MATERIALS AND METHODS: The study was carried out during the period of 2011-2015 and blood samples were collected from suspected amoebiasis cases who were attending the clinics of Medicine and Paediatrics department, JIPMER. A total of 200 sera samples which included 100 Amoebic Liver Abscess (ALA), 50 cases of other parasitic infections and liver diseases and 50 presumed healthy controls were examined by IHA and commercial ELISA. In brief, chick cells were stabilized by Double Aldehyde Sensitization (DAS) method. Optimum Sensitizing Dose (OSD) of the antigen was determined. The test was performed in a U-bottomed microtiter plate with recombinant amoebic antigen (12.5MUg/ml), incubated at Room Temperature (RT) for 2 hours. RIDASCREEN Entamoeba IgG ELISA kit which is commercially available was used to evaluate the samples as per manufacturer's instruction. RESULTS: The overall sensitivity and specificity of the IHA was 62% and 96%, respectively when compared to ELISA having sensitivity and specificity of 69% and 90%, respectively. The positive predictive value of the IHA was 91% while negative predictive value was 79%. Similarly, the positive predictive value of the ELISA was 87% while negative predictive value was 74%. CONCLUSION: As serology heavily suffers due to lack of a standardised test system employing the native antigen, there arises need to identify alternative source of recombinant antigen which could effectively improvise the existing lacunae in the current system. Serology acts as an adjunct in clinical decision making if properly interpreted. This is an important consideration in endemic region where health services resources are limited. PMID- 27656438 TI - Blood Stream Infection by Escherchia hermannii in a Neonate. AB - Escherichia hermannii is a Gram negative bacillus, facultative anaerobe and member of the family Enterobacteriaceae. It was earlier classified as Enteric Group 11 by the Enteric Section of Centers for Disease Control (CDC) and was reported in the clinical laboratory as a yellow pigmented E. coli strain. On the basis of its unique genomic features, this organism was labelled as a distinct species in 1982. A successfully treated case of a blood stream infection by E. hermannii in a neonate is being described. PMID- 27656437 TI - Antifungal Activity of Cinnamon Oil and Olive Oil against Candida Spp. Isolated from Blood Stream Infections. AB - INTRODUCTION: Recently non-albicans Candida has emerged as a major cause of morbidity and mortality in blood stream infections. Some species of the Candida are becoming increasingly resistant to first line and second line antifungals such as echinocandins and fluconazole. In view of increasing global antifungal resistance, role of alternative and better antifungals like natural plant products need to be explored. Essential oils are known to exhibit antimicrobial activity against various fungi. Hence, we evaluated the efficacy of cinnamon oil and olive oil against Candida spp. AIM: To evaluate the invitro antifungal activity of olive oil and cinnamon oil against blood stream Candida isolates. MATERIALS AND METHODS: The present prospective observational study was conducted in the Department of Microbiology at a tertiary care teaching hospital during one year June 2011-July 2012. Blood samples were collected from 1376 patients clinically suspected to have fungal septicaemia, out of which 100 (7.2%) Candida isolates obtained, were speciated by conventional methods. Antifungal susceptibility testing of all the isolates was done against fluconazole, voriconazole as per NCCL (M27-A2) and against olive oil and cinnamon oil by agar well diffusion method. RESULTS: Prevalence of Candidemia was 7.26%. C. albicans (85.3%) and C. parapsilosis (85.7%) were most sensitive to fluconazole followed by C. tropicalis (67.4%). All isolates were 100% sensitive to voriconazole. Both oils were found to be effective against nearly 50% of the Candida isolates. About 55.5% of fluconazole resistant C. krusei strains were sensitive to olive and cinnamon oil. CONCLUSION: Fluconazole resistant non-albicans Candida has emerged as major cause of Candidemia. Cinnamon and olive oil show marked sensitivity against albicans and non-albicans spp. PMID- 27656439 TI - Pefloxacin as a Surrogate Marker for Fluoroquinolone Susceptibility for Salmonella typhi: Problems and Prospects. PMID- 27656440 TI - Cefuroxime Prophylaxis in Total Joint Arthroplasty: Need for Antibiotic Stewardship. PMID- 27656441 TI - Commercial Disinfectants During Disinfection Process Validation: More Failures than Success. AB - INTRODUCTION: Disinfection process validation is mandatory before introduction of a new disinfectant in hospital services. Commercial disinfection brands often question existing hospital policy claiming greater efficacy and lack of toxicity of their products. Inadvertent inadequate disinfection leads to morbidity, patient's economic burden, and the risk of mortality. AIM: To evaluate commercial disinfectants for high, intermediate and low-level disinfection so as to identify utility for our routine situations. MATERIALS AND METHODS: This laboratory based experiment was conducted at St Stephen Hospital, Delhi during July-September 2013. Twelve commercial disinfectants: Sanidex(r), Sanocid(r), Cidex(r), SekuSept Aktiv(r), BIB Forte(r), Alprojet W(r), Desnet(r), Sanihygiene(r), Incidin(r), D125(r), Lonzagard(r), and Glutishield(r) were tested. Time-kill assay (suspension test) was performed against six indicator bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella Typhi, Bacillus cereus, and Mycobacterium fortuitum). Low and high inoculum (final concentrations 1.5X10(6) and 9X10(6) cfu/ml) of the first five bacteria while only low level of M. fortuitum was tested. RESULTS: Cidex(r) (2.4% Glutaraldehyde) performed best as high level disinfectant while newer quarternary ammonium compounds (QACs) (Incidin(r), D125(r), and Lonzagard(r)) were good at low level disinfection. Sanidex(r) (0.55% Ortho-pthalaldehyde) though mycobactericidal took 10 minutes for sporicidal activity. Older QAC containing BIB Forte(r) and Desnet(r) took 20 minutes to fully inhibit P. aeruginosa. All disinfectants effectively reduced S. Typhi to zero counts within 5 minutes. CONCLUSION: Cidex(r) is a good high-level disinfectant while newer QACs (Incidin(r), D125(r), and Lonzagard(r)) were capable low-level disinfectants. PMID- 27656442 TI - Morphological Patterns of Intracranial Lesions in a Tertiary Care Hospital in North Karnataka: A Clinicopathological and Immunohistochemical Study. AB - INTRODUCTION: An "Intra-cranial space occupying lesion" (ICSOL)is defined as a mass lesion in the cranial cavity with a diverse aetiology like benign or malignant neoplasm, inflammatory or parasitic lesion, haematoma, or arterio venous malformation. Central nervous system neoplasms represent a unique, heterogenous population of neoplasms constituting 1.9% of all malignant tumours in India. A broad spectrum of non-neoplastic conditions can mimic a brain tumour, both clinically and radiologically and these patients undergo biopsy. In such cases, the pathologist can readily differentiate between neoplastic and non neoplastic imitators. AIM: The present study attempts to provide preliminary data on morphological patterns of intracranial lesions in North Karnataka region and to study clinicopathological spectrum with correlation of radiological findings of ICSOL. Special emphasis is made on the utility of special stains and IHC markers in CNS tumours. MATERIALS AND METHODS: This retrospective and prospective descriptive study was performed on biopsy specimen of ICSOL received from Departmnet of Neurosurgery, Basaveshwar Teaching Hospital, Kalaburgi. The study period was from January 2012 to June 2013 retrospectively and July 2013 to June 2015 prospectively. All specimens were preserved in 10% formalin and allowed to fix for 24 hours. The haematoxylin and eosin stained sections of the CNS lesions were obtained by routine processing and paraffin embedding. Special stains and IHC were done wherever appropriate. RESULTS: Sixty two cases of CNS lesions were studied, of which 12 (19.4%) cases were non neoplastic with six (50%) being cystic lesions and four (33.4%) were cerebral abscess. The neoplastic lesions comprised of 50 (80.6%) cases, which included 48 (96%) primary and two (4%) metastatic lesions. Among primary tumours, gliomas constituted the largest category of 24 (50%) cases with 16.7% being Glioblastoma Multiforme (GBM) and pilocytic astrocytomas each, followed by schwannomas (14%) and meningothelial tumours (12%). Majority were Grade I among gliomas and tumour of meninges with 37.5% and 87.5% respectively. Mean age of the patients was 26.72+/-11.2 (range: 0.4 to 80) years. Male to female ratio was 1:1.14. GFAP was demonstrated in astrocytomas, mixed gliomas and gliosarcoma. CONCLUSION: The surgical pathologist plays an important role in accurate diagnosis of various lesions of CNS which will be of immense help for patient prognosis and treatment. Immunohistochemistry is currently being employed to assist in the diagnosis of brain tumours. PMID- 27656443 TI - Expression of ERalpha and PR in Various Morphological Patterns of Abnormal Uterine Bleeding-Endometrial causes in Reproductive Age Group. AB - INTRODUCTION: Abnormal Uterine Bleeding (AUB) is most common gynaecological problem but its management is not well defined. So FIGO/PALMCOEIN classification was developed to provide clear management options as treatment is different in PALM and AUB-E group. FIGO/PALM-COEIN classification and immunohistochemistry with ERalpha and PR expression in AUB-E group will be helpful in management of these patients, thus preventing surgical interventions. AIM: To study histomorphological classification according to FIGO/PALM-COEIN classification in patients presenting with AUB into PALM and AUB-E group. To study the receptor expression of ERalpha and PR in AUB-E group. MATERIALS AND METHODS: This cross sectional study was performed in patients presenting with AUB in reproductive age group (15-45 years). Six hundred endometrial specimens were stained with H&E for histolomorphological examination and classified as per FIGO/PALM-COEIN classification of AUB in non-gravid women in reproductive age group. Fifty endometrial biopsies were of pregnancy and pregnancy related complications and were excluded from study. A total of 550 samples were evaluated in present study. IHC for quantification of ERalpha and PR expression was carried out in AUB-E (100) cases and control group endometrium (20) cases due to technical constraints. STATISTICAL ANALYSIS: Unpaired student t-test was performed. p-value <= 0.05 was taken as critical level of significance. RESULTS: Endometrial (58.19%) (AUB-E) causes were most common cause of AUB. Most common morphology was AUB-E (Proliferative endometrium), AUB-L (Leiomyoma) and AUB-E (Secretory endometrium) respectively. Statistically significant expression of ERalpha and PR was found in AUB-E endometrium as compared to control group endometrium. In Non secretory/Proliferative endometrium AUB-E group. Proliferative endometrium and hyperplasia without atypia had significant expression of ERalpha and PR in glands and stroma when compared with proliferative phase control group endometrium. But disordered proliferative endometrium had only significant PR expression in stroma. When secretory phase endometrium was compared with control group secretory phase significant expression for PR was noted only in stroma. CONCLUSION: FIGO/PALM-COEIN classification will be helpful in deciding treatment of AUB cases. Study of receptor expression in AUB-E group will help in providing evidence based treatment and prevent from surgical procedures like hysterectomy and endometrial ablation. PMID- 27656444 TI - Clinicopathological Features of Intraductal Papillary Mucinous Neoplasms of Pancreas in a Tertiary Care Center: A 14 Year Retrospective Study. AB - INTRODUCTION: Pancreatic surgeries are usually performed for inflammatory conditions and neoplasms. Intraductal Papillary Mucinous Neoplasm (IPMN) account for approximately 5-7% of all pancreatic neoplasms in western literature. To the best of our knowledge, there has been no published literature in Indian subcontinent on IPMN. AIM: To assess the spectrum of different pancreatic pathologies on pancreatic resection specimens. Also, to review and share the experience on the clinicopathological features of IPMNs in our institute. MATERIALS AND METHODS: This was a 14 year retrospective study of all cases where pancreatic surgeries were done for pancreatic pathology. The slides and blocks of diagnosed cases of IPMNs were retrieved from the department archives, reviewed and a detailed study on the histopathological features was done. RESULTS: Among the 377 pancreatic surgical specimens, pancreatitis was the most common diagnosis followed by exocrine neoplasms and endocrine neoplasms. IPMN constituted 3.2 % of all pancreatic neoplasms. Histologically, the most common type was the gastric foveolar type. Pancreatobiliary type was aggressive and associated with an invasive component and had evidence of metastasis on follow up. CONCLUSION: IPMNs are rare neoplasms of pancreas with a male predominance. They are usually indolent except for the pancreatobiliary type which may have an aggressive course, often associated with an invasive adenocarcinoma component. Diligent follow up is recommended. PMID- 27656445 TI - The Study of MIB-1 LI and CD 34 As A Marker of Proliferative Activity and Angiogenesis in Different Grades of Meningioma. AB - INTRODUCTION: Meningiomas comprise 24-30% of all tumours occurring in the central nervous system. Conventional morphologic critera as studied in routine Haematoxylin and Eosin stained sections (H & E) may not be accurate in grading and assessing prognosis in small stereotactic biopsy specimens. Thus, arises the need for objective methods for assessing tumour biology. Angiogenesis is a key event in the spread of tumours and denotes a poor prognosis. Intratumoural Microvessel Density (MVD) helps in quantification of angiogenesis. AIM: To measure the proliferative index by MIB-1 and correlate it with the WHO grading of meningiomas. Also to assess the expression of CD34 in various grades of meningioma and evaluate their angiogenic potential by calculating MVD. MATERIALS AND METHODS: Paraffin blocks of 30 surgically resected cases, 10 each of grade I, II and III meningiomas were reviewed. Tumours were graded and subtyped as per WHO criteria. Immunohistochemical staining was done with MIB-1 and CD 34 antibodies. Statistical analysis was performed using Mann - Whitney U test. p-value of < 0.05 was considered significant. RESULTS: The male to female ratio overall was 1:1. The age of the patients ranged from 18-81 years. A 73% of patients had raised intracranial pressure and 18.4% of patients presented with seizures. The mean +/- SD MIB-1 LI was 1.14 +/- 0.84, 8.94 +/- 2.73 and 35.62 +/- 4.44 in grade I, II and III tumours respectively which was statistically significant. (p< 0.01). The mean +/- SD MVD was 49.67 +/- 22.35, 41.37 +/- 7.45 and 47.86 +/- 10.77 respectively in grade I, II and III tumours (p NS). CONCLUSION: MIB-1 LI is an important complementary tool to accurately grade meningothelial tumours and assess tumour biology. Specific cycling endothelial markers along with CD 34 & MVD could be used to assess the prognosis of these tumours. PMID- 27656446 TI - Diagnostic Pitfalls in Papillary Lesions of the Breast: Experience from a Single Tertiary Care Center. AB - INTRODUCTION: Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. AIMS: This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. MATERIALS AND METHODS: A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient's clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. RESULTS: During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. CONCLUSION: Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis. PMID- 27656447 TI - Actinomycosis of Finger: Case Report and Review of the Literature. AB - Cutaneous actinomycosis of finger is very unusual, chronic granulomatous disease caused by a group of anaerobic or microaerophilic Gram-positive filamentous bacteria that normally colonize the mouth, colon and urogenital tract. Actinomycosis of finger is rare but clinically important condition that requires suitable evaluation for guiding appropriate therapy. We hereby report a case of cutaneous actinomycosis of the right finger- a rare site, in a 34-year-old female patient which underwent usual treatment of surgical excision. This patient complained of existence of a mass and tenderness in the pulp of right index finger. The X-ray of hand revealed no significant abnormality. The patient was treated successfully with surgical excision. Surgery detected five small nodules measuring 0.5 to 1 cm in size. Histopathologic examination of the biopsy from the lesions confirmed diagnosis of cutaneous actinomycosis. Here, we report a cutaneous actinomycosis in a 34-year-old female located in the index finger. PMID- 27656448 TI - MPV in Uncontrolled & Controlled Diabetics- Its Role as an Indicator of Vascular Complication. AB - INTRODUCTION: Platelets are tiny, disc-shaped, non-nucleated structures derived from megakaryocytes. The morphological differences in measuring Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) of platelets have important implications for assessing the functional expressions of platelets. Electron microscopy reveals the presence of glycogen as prominent masses in platelets. MPV values have been generally reported to be very high in individuals with uncontrolled diabetes mellitus (DM). AIM: This study aimed to determine and compare the MPV values in uncontrolled and controlled group of Type-2 Diabetics along with healthy non-diabetic people and to correlate MPV values with age, sex and glycosylated haemoglobin (HbA1c) levels in diabetic groups. This study also aimed to determine the prevalence of retinopathy in uncontrolled and controlled group of diabetic patients. MATERIALS AND METHODS: This case control study was carried out in our institution for 1 year. The patients were grouped as uncontrolled group of diabetic patients and controlled group of diabetic patients based on their HbA1c levels. 106 uncontrolled diabetic patients and 100 controlled diabetic patients were included, with 100 non-diabetic subjects as controls. Patient's profile which included all demographic particulars and medical history was obtained. Fundus examination and other ophthalmic findings of 50 uncontrolled and 50 controlled diabetic cases were recorded. The findings were analysed statistically using IBM SPSS software. RESULTS: In uncontrolled group of 106 diabetic patients, 54 patients were males and 52 patients were females and the mean age was 51.63+/-11.04, mean HbA1c was 9.86+/-1.91% and mean MPV was 8.93+/-0.90fl. In controlled group of 100 diabetic patients, 49 patients were males and 51 patients were females and the mean age was 47.88+/-15.17, mean HbA1c was 6.08+/-0.49% and mean MPV was 8.106 +/- 0.72fl. In 100 non-diabetic controls 77 patients were males and 23 patients were females and the mean age was 37.97+/ 9.69 and mean MPV was 8.02+/-0.86fl. Among 50 cases of uncontrolled DM, 14 uncontrolled DM patients had diabetic retinopathy with an average MPV of about 9.2+/-0.61fl and mean HbA1c of 10.6+/-1.98% whereas, 30 uncontrolled patients with no evidence of retinopathy with an average MPV of about 8.39+/-0.676 fl and mean HbA1C of 9.18+/-1.91%. CONCLUSION: MPV values are higher in uncontrolled DM patients when compared with controlled DM patients and a higher percentage of them develop microvascular complications like Diabetic Retinopathy suggesting that mean platelet volume could indicate and play a more important role in the detection of vascular complications of Diabetes. PMID- 27656450 TI - Solid Pseudopapillary Tumour of Extrapancreatic Origin Presenting as Mesenteric Cystic Mass: A Diagnostic Dilemma. AB - Solid Pseudopapillary Tumour (SPT) is a rare and distinctive pancreatic exocrine neoplasm. Even Rarely, such primary SPT may originate from ectopic pancreatic tissues. We are hereby presenting one such unique case, where a 50-year-old female presented with pain and a mid-abdominal lump. Radiology revealed a well defined outline located adjacent to the tail of pancreas. The excised mass was 19*14*7cm in dimension having zones of haemorrhage, necrosis and cystic spaces filled with necrotic debris. Microscopic examination confirmed the diagnosis of SPT. SPT originating in extrapancreatic location may mimic an ovarian cystic tumours or mesenteric cysts, its proper identification is crucial. PMID- 27656449 TI - Renal Biopsy Findings in Patients with Hypothyroidism: Report of 16 cases. AB - INTRODUCTION: Hypothyroidism is prevalent in India. Its association with renal diseases though not very common but have been described in many studies. Here we are reporting renal biopsy findings in 16 cases, all of whom were already diagnosed cases of hypothyroidism. AIM: To study renal parenchymal diseases associated in patients with hypothyroidism. MATERIALS AND METHODS: Formalin fixed paraffin embedded sections of renal biopsy were examined after staining with H&E, PAS and Acid Fuschin Orange G (AFOG) stain. Serum urea/creatinine measurements done by semi-autoanalysers and urine analysis were done by using urine strips and light microscopy. RESULTS: In 16 cases, M:F ratio was 9:7. Duration of disease varied from 6 months to 14 years. Blood urea and serum creatinine were raised in 10 cases (62.5%) and nephrotic range proteinuria was present in 13 cases (81.25%). Two of the patients had co existing systemic lupus erythaematous. Renal pathology revealed membranous glomerulonephritis (GN) in both cases. In renal biopsy seven cases (43.75%) had pure Membranous Glomerulonephritis (MGN), 4 cases (25%) had mixture of Mesan-gial cell proliferation and membranous Glomerulonephritis(GN) also called MembranoProliferative GN (MPGN). Another four cases (25%) had Focal Segmental Glomerulosclerosis (FSGS) with chronic interstitial nephritis and one case was having minimal change disease. CONCLUSION: Thus present study concludes that hypothyroidism can cause renal parenchymal disease like membranous GN, mesangiocapillary GN which is also called as membranoproliferative GN and FSGS. PMID- 27656451 TI - Massive Ovarian Oedema- A Case Report. AB - Massive ovarian oedema is defined by WHO as formation of tumour like enlargement of one or both ovaries by oedema fluid. We report a case of a 18-year-old unmarried girl who presented with three months amenorrhoea and left sided lower abdominal pain with clinical and radiological diagnosis of cystic ovarian neoplasm. Patient underwent lapratomy with left salpingo-oophorectomy. A definitive diagnosis of Massive Ovarian Oedema (MOE) was offered on histopathological examination. The MOE should be differentiated from ovarian fibromatosis, ovarian fibroma, sclerosing stromal tumour and ovarian myxoma. The usual management of massive oedema of ovary is unilateral salpingo-oophorectomy, as the lesion is mistaken for primary ovarian neoplasm at laparotomy. Recognition of MOE is of great importance to prevent unnecessary oophorectomy in young patients and can be managed conservatively. We report this case of MOE for its rarity. PMID- 27656452 TI - Pheohyphomycosis in Renal Transplant Recipient Presenting as a Rare Case of Submandibular Salivary Gland Swelling. AB - Renal transplant patients are at high risk of developing various infections causing morbidity and mortality. Invasive fungal infection has been recognized as a significant complication of organ transplantation. The major fungal infections in these patients are due to candida, aspergillus and mucormycosis. However, infection because of infrequently encountered fungi like hyaline molds, dematiaceous filamentous fungi and zygomycetes are increasing in immunocompromised hosts. Dematiaceous fungi are recognized pathogens in organ transplant recipients with skin and soft tissue infection. We report the case of a 37-year-old man, a renal transplant recipient who developed an asymptomatic dematiaceous fungal infection in submandibular salivary gland. He recovered after excision and antifungal therapy. PMID- 27656453 TI - Cytodiagnosis of Extraskeletal Ewing's Sarcoma and its Confirmation by Fluorescence in situ Hybridization. AB - Extraskeletal Ewing's sarcoma is an aggressive malignant small round cell tumour usually occuring in children and adolescents. It needs to be differentiated from other malignant small round cell tumours and immunohistochemistry plays a pivotal role in establishing the diagnosis. Fluorescence in situ hybridization or real time-polymerase chain reaction helps in confirming the diagnosis by demonstration of EWS-FLI1 translocation, which is found in approximately 85% of the cases. We report a case of extraskeletal Ewing's sarcoma in a10-year-old male, who presented with a right gluteal region mass. Fine needle aspiration and cell block preparation followed by a panel of immunohistochemical markers were performed. Immunohistochemistry for CD99 and FLI1 was positive. EWS-FLI1 translocation was confirmed by fluorescence in situ hybridization. PMID- 27656454 TI - Incidental Detection of Hairy Cell Leukaemia with Herpes Simplex Virus (HSV) Related Lip Ulcer Mimicking Carcinoma. AB - Hairy cell leukemia is a chronic lympho-proliferative disease. It is indolent but progressive in nature. It arises from B-cell lineage. We report an incidentally detected case of Hairy Cell Leukaemia (HCL) in a 55-year-old male patient with Herpes simplex virus (HSV) - related lip ulcer mimicking squamous cell carcinoma. Clinically the patient presented with lip ulceration without pain. He was found to have moderate hepatosplenomegaly and pancytopenia on general examination. Bone marrow aspiration and flow cytometric immunophenotyping revealed HCL. The oral lesion resolved after antiviral therapy. The intriguing possibility of a combined pathogenesis for the two disorders is considered, as HCL is known to be associated with immunosuppression, second malignancies and the production of cytokines promoting epithelial growth. PMID- 27656455 TI - Chondroblastic Variant of Osteosarcoma of Mandible: Report of a Rare Case. AB - Osteosarcoma (OS), a common malignant tumour of the long bones, is rarely seen in the craniofacial region (5-8%). Though it's aetiology is unknown, previous radiotherapy, Pagets disease, Retinoblastoma and benign bone lesions such as fibrous dysplasia are considered as predisposing factors. It is seen commonly in adults between the third and fourth decades of life, in the Gnathic location mandible. We report a rare case of chondroblastic variant of OS of the right mandible, in a 35-year-old male, who underwent right segmental mandibulectomy with fibular graft reconstruction and is having disease free survival one and half years post surgery. Craniofacial OSs, are considered a separate category in view of their low histologic grade, less frequent metastases and better prognosis. Hence the diagnosis of this variant is important. This case is reported because of its rarity and typical histopathological features. PMID- 27656456 TI - Hepatosplenic T Cell Lymphoma in an Immunocompetent Female Diagnosed using Flow Cytometry: A Rare Clinical Entity. AB - Hepatosplenic T-cell lymphoma is a rare haematopoietic malignancy that comprises less than 1% of Non-Hodgkin lymphomas. We are reporting a case of a 26-year-old female, who presented with pallor, weight loss, jaundice, pancytopenia and hepatosplenomegaly. The bone marrow examination showed infiltration by lymphoid cells. These cells on flow cytometric evaluation showed the phenotype of hepatosplenic T cell lymphoma. The cells were positive for CD3, CD8, CD56 and TCR gammadelta and negative for CD5, CD4, CD8, CD16, CD57, TCRalphabeta along with B cell markers. This case is reported for being a rare clinical entity and its presence in an immunocompetent female making it rarer. PMID- 27656457 TI - Spindle Cell Variant of Embryonal Rhabdomyosarcoma: A Rare Entity with Diagnostic Challenges. AB - The spindle cell variant of embryonal rhabdomyosarcoma is a rare and a better differentiated variant of embryonal rhabdomyosarcoma, having a better prognosis compared to other types of rhabdomyosarcomas. So, it needs to be distinguished from classical forms of the neoplasm. Its morphological resemblance to spindle cell neoplasms like leiomyosarcomas and fibrosarcomas may pose diagnostic difficulties for the pathologist. This problem can be overcome by careful search for rhabdomyoblasts in sections, which are usually few, and Immunohistochemistry for myogenin. In the present case, a 15-year-old female presented with a progressively increasing swelling in the right upper eyelid, which was diagnosed as a rare variant of rhabdomyosarcoma. We have also attempted to discuss its differential diagnosis, and to emphasize the fact that this rare entity may be misdiagnosed. PMID- 27656458 TI - Two Unusual Cases of Acinic Cell Carcinoma: Role of Cytology with Histological Corelation. AB - Acinic Cell Carcinoma (AcCC) is a slow growing, malignant tumour of salivary glands, predominantly found in parotid gland and rarely in submandibular gland or minor salivary glands. Rarely, the tumour can arise in Heterotopic Salivary Gland Tissue (HSGT) and can present bilaterally. Synchronous contralateral tumour or tumour arising in HSGT is easily missed clinically. Fine Needle Aspiration Cytology (FNAC) is an important preoperative diagnostic investigation in cases of AcCC. Sometimes its diagnosis on cytology is very difficult and it is easily misdiagnosed as benign, affecting the long term prognosis. Here, we present two unusual cases of AcCC. One developed in HSGT and the other was synchronous bilateral. Though the histological features of AcCC appear to be characteristic but clinical suspicion and cytological features have been described as equally important for preoperative diagnosis. Present cases highlight the importance of a cytopathologist who plays an important role in its preliminary diagnosis. PMID- 27656459 TI - A Retrospective Analysis of Reporting of Adverse Drug Reactions in a Tertiary Care Teaching Hospital: One Year Survey. AB - INTRODUCTION: Pharmacovigilance (PV) is related to detection, assessment, understanding and prevention of Adverse Drug Reactions (ADRs) which are incurred when drug is made available in the market and used in different physiological conditions. In many countries, ADRs ranks among the top ten leading cause of morbidity and mortality. There is a lack of formal culture for monitoring and reporting of ADRs in India, with ADR reporting rate being only 1% as compared to 5% in world. This type of academic detailing activity helps to create awareness of ADR reporting in the institutions. AIM: This study was planned to evaluate and analyse the incidence and patterns of ADRs in various inpatient and outpatient departments of hospital. MATERIALS AND METHODS: This was an observational, retrospective and record based study conducted by analysing the spontaneous ADR forms, collected over a period of 12 months (September 2014 to August 2015) at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. RESULTS: During the period of one year, 292 ADR forms were collected from 4,34,965 patients attending OPD and inpatients of the hospital. Incidence of ADR was 0.67 per thousand patients and average of around 24 ADR collected per month. Male:Female ratio was 1.30. Adolescent (16-30 yr) was the most common age group affected. Department of Skin and VD reported the maximum number of ADRs (33.22%), followed by the Departments of Oncology (18.84%). Antibiotics were the most common drug implicated followed by anticancer drugs. CONCLUSION: ADR reporting is an ongoing and continuous process. Studies from the institute helps to identify and rectify the problems related to ADR reporting. Pitfalls can be addressed by creating awareness among physicians and the patients to achieve finally the goal of Pharmacovigilant India. PMID- 27656460 TI - Utilization of Medicines Available at Home by General Population of Rural and Urban Set Up of Western India. AB - INTRODUCTION: In India, medicines are procured with prescription or without prescription by patients, which are kept at home and often are utilized in inappropriate manner. It may remain unused, get expired or may be repeated in the way of self medication. So there remains an increase chance of self-medication compared to prescribed drugs. AIM: This study was aimed to explore the utilization pattern of medicines available at home with special attention to the types of medicine (with or without prescription) and their appropriate utilization (dosage compliance) and intended self-medication. MATERIALS AND METHODS: A cross-sectional study was conducted in Anand district of Gujarat, India during the year 2012- 2014 after Human Research Ethics Committee (HREC) approval. Data were collected from 800 houses, 400 each from urban and rural areas and then analysed for the details of medicines available in the house as: (i) number of homes having medicines; (ii) number of formulations with and without prescriptions; (iii) number of formulations with package inserts & expired formulations; (iv) Dosage forms of medicines; (v) pharmacological class wise distribution of medicines; (vi) status of the medicine use whether for current use, future use or leftover; and (vii) Appropriateness of medicines with and without prescription in relation to dose and duration of treatment. RESULTS: Medicines were available in 93.75% houses. More medicine formulations (16.76%) were found without prescription in urban area than in rural (11.82%). Highest number of dosage forms found, were that of tablets (62%). Among the prescribed medicines, majority of medicines were from cardiovascular disease (19.88%) and from without prescription medicines, Non-Steroidal Antiinflammatory Drugs (NSAIDs) were the major group available at houses (35.13%). The leftover medicines with prescription were 20.39% and without prescription medicines were 13.37%. Appropriate dose and duration of medicines were followed more significantly by urban people than the rural. Only 2.91% medicines were found along with package inserts and 2.94% crossed the expiry dates. CONCLUSION: The evaluation of utilization of medicines, in urban and rural population describes high drug storage, higher leftover medicines and inappropriate use of medicines and many self medicated by patients which suggests the need to educate the patients about proper and rational use of medicines. PMID- 27656461 TI - Is This a Drug?" Answers From Medical Students in a Tertiary Care Teaching Hospital in Eastern India. AB - INTRODUCTION: World Health Organization (WHO) defines what is drug and what is not. Second year MBBS students learn the principles of Pharmacology that they use in their later clinical practice life. The aim of the survey was to determine how medical students classify a range of preparations they might encounter in their professional lives and whether a brand name or a commercial preparation of a drug would influence their decision in the categorization of the preparation as a 'drug' or 'not a drug'. AIM: To assess the knowledge of medical students, if a substance or product is a drug. MATERIALS AND METHODS: We surveyed 2 concurrent years of medical students to classify 60 candidate medicinal preparations into "drug" and "not-drug" from a validated questionnaire. The candidate preparations were named either in generic or in their commercially available forms and they were all essential drugs as per WHO definition. RESULTS: The two groups of students, A and B, included 192 and 215 students respectively. Demographically there was little difference in the two groups. Agents like Aspirin, Paracetamol, Amphetamine, Salbutamol, Atropine, Dextromethorphan, Codeine, Diazepam, Ciprofloxacin ear drops, Levonorgestrol, Neosporin eye ointment, Furosemide, Metronidazole, Penicillin, Sorbitrate, Lignocaine, Methotrexate, Penicillin, Zolpidem and Thalidomide received almost unanimous votes as drugs. Arsenic trioxide, Fentanyl and petroleum jelly were considered to be "non-drugs" by most participants. The two groups did not differ significantly in their responses. CONCLUSION: Some major lacunae were noted in the knowledge of the participating students despite book teaching on the definition of a drug. Drugs used for prophylaxis and those used in physiological conditions or topically, were often missed. These gaps need to be filled by more emphasis on definition of a drug and its clinical applicability based on example and case based studies. PMID- 27656462 TI - Bedaquiline: A Novel Antitubercular Agent for the Treatment of Multidrug Resistant Tuberculosis. AB - The developing countries are having an abruptly growing number of drug resistant tuberculosis cases. Multidrug-resistant tuberculosis (MDR-TB) is a type of TB in which the strain of Mycobacterium tuberculosis is resistant to at least Isoniazid and Rifampicin, the two most effective of the four first-line TB drugs (the other two drugs being Ethambutol and Pyrazinamide). The management of such cases is complex and requires a treatment for 24-27 months. The current guidelines available for the management of this type of TB are largely based on the second line TB drugs which are relatively costly, less efficacious and are associated with greater side-effects. The introduction of newer drugs to cater to the high mortality and early sputum culture conversion in the MDR-TB cases is an absolute essential. In the present article, the authors discuss about the introduction of a newer drug named Bedaquiline for the control of MDR-TB. PMID- 27656464 TI - Health System Competency for Maternal Health Services in Balasore District and Jaleswar Block, Balasore, Odisha, India: An Assessment. AB - INTRODUCTION: A competent health system is of paramount importance in delivering the desired health services in a particular community. AIM: The broad objective of this study was to assess the health system competency for the maternal health services in Balasore District and Jaleswar block of Balasore district, Odisha, India. MATERIALS AND METHODS: A mixed method approach was adopted in order to understand the health system competency for maternal health services in the study area. RESULTS: There was poor accessibility through road, poor electricity connection and piped water for the health care centers in the district. Even, existing Primary Health Centres (PHCs) lack ECG and X-Ray machines for proper diagnostic services which jeopardize the catering of health services. Community Health Centres (CHC) lack basic diagnostic and ambulance services making the tribal pockets inaccessible. The tribal dominated Jaleswar block shows poor performance in terms of total registered Antenatal Checkups (ANC) (only 77%). A gradual decrease in the rate of ANC, from first to fourthcheckup, was observed in the district. CONCLUSION: Lack of public health infrastructure in general and non compliance to Indian Public Health Standards (IPHS) in particular, affect the health of tribal women resulting in lack of interest in availing the institutional delivery services and other pertinent maternal health services. PMID- 27656463 TI - The rs2070895 (-250G/A) Single Nucleotide Polymorphism in Hepatic Lipase (HL) Gene and the Risk of Coronary Artery Disease in North Indian Population: A Case Control Study. AB - INTRODUCTION: Several Single Nucleotide Polymorphisms (SNPs) in lipid transport genes have been shown to be associated with Coronary Artery Disease (CAD). The Hepatic Lipase (HL)glycoprotein is a key component that catalyzes the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. AIM: We studied whether the HL gene-250G/A polymorphism affect blood lipid level and the CAD in a North Indian population. MATERIALS AND METHODS: A total number of 477 subjects were enrolled in the study after approval of the Institutional Ethics Committee. Out of 477 subjects, 233 were with coronary artery disease as study group and 244 subjects without coronary artery disease as control group. All subjects recruited with matched ethnicity in age group of 40-70 years. Blood samples were collected in EDTA vials and genomic DNA was extracted from blood using the phenol-chloroform method. Lipid profile was estimated by using a commercially available kit. Polymorphisms in the HL (-250 G/A) gene were analysed by using restriction fragment length polymorphism-polymerase chain reaction (PCR RFLP) method. The effect of this polymorphism on plasma lipids, lipoproteins and coronary artery disease was determined. RESULTS: In Human Hepatic Lipase (LIPC) 250G/A genotype, the frequencies of GG, GA and AA genotype in CAD group was 80.69%, 15.45% and 3.86%, respectively; in the control group, the corresponding frequencies were 90.16%, 9.02% and 0.82%, respectively. A significant difference was found in the genotype (LIPC-250G/A) distribution between the two groups. Further logistic regression analysis indicated that the GA and AA genotypes in SNP-250G/A were significantly associated with CAD in all genetic models (In codominant model- GA vs. GG, OR=1.91, 95% CI=1. 09-3.37, p=0. 03 and AA vs. GG, OR= 5.26, 95% CI= 1.10-24.60, p=0.04; in dominant model- GA+AA vs. GG, OR=2.19, p=0.004 and in recessive model- AA vs. GG+GA, OR=5.26, p=0.04 whereas, A allele at nucleotide -250G/A in the LIPC gene had an association with increased risk of CAD (OR=2.33, p=<0.008). CONCLUSION: Our findings indicated that the higher frequency of a dominant model (GA+AA) as well as mutant allele A of LIPC-250 G/A polymorphism is significantly associated with risk of CAD and the lipid profile can be used as a predictor of CAD. PMID- 27656465 TI - Development and Validation of a Questionnaire to Measure Iranian Nurses' Knowledge, Attitude and Practice Regarding Disaster Preparedness. AB - INTRODUCTION: Despite the key role of Iranian nurses throughout disaster management, there is no instrument available to examine nurses' current disaster preparation levels. AIM: The aim of this study was to develop and analyse the reliability and validity of a questionnaire on the nurses' knowledge, attitude and practice of disaster preparedness. MATERIALS AND METHODS: The scale was developed based on a comprehensive literature review and applied to 112 nurses in three public educational center affiliated to Ilam University of Medical Sciences, Ilam, Iran. Relibility was obtained using the test-retest method. Cronbach's alpha was used to verify internal consistency. Exploratory factor analysis was used to assess the validity of the questionnaire. RESULTS: Explanatory factor analysis using varimax rotation revealed seven main factors associated with the nurses' knowledge, attitude and practice regarding disaster preparedness. The questionnaire overall internal consistency using Cronbach's alpha was 0.785, showing acceptable internal consistency. The intraclass correlation coefficient using Test-retest method was 0.82. Total variance was 67.57%. CONCLUSION: The instrument has satisfactory reliability and validity indices and can be used to measure nurses' knowledge, attitude and practice regarding disaster preparedness. PMID- 27656467 TI - The Proposal of a BDS Syllabus Framework to Suit Choice Based Credit System (CBCS). AB - INTRODUCTION: Higher education takes a new dimension universally in the form of choice based Credit System (CBCS). In India, the University Grants Commission (UGC) has made CBCS mandatory in all fields except for Health Profession. Not much attempts were made in designing a BDS syllabus to suit CBCS. AIM: Aim of the study was to propose a model dental syllabus to fit into choice based credit system. MATERIALS AND METHODS: A model BDS syllabus Prototype for CBCS was designed based on the UGC guidelines for terms as well as calculations for CBCS. Engineering curriculum models from IIT and Anna University were also referred to. RESULTS: Semester based BDS syllabus was designed without changing the norms of Dental Council of India (DCI). All the must know areas of the subjects were considered as "core" areas and the desirable and nice to know areas are left for "electives" by the students. By this method, none of the subject was left out at the same time students are provided with electives to learn deeper on their topics of choice. CONCLUSION: The existing BDS syllabus can be effectively modified by incorporating few changes based on the UGC regulations for Choice based credit system. The proposed framework gives an insight on the nature of modifications that are needed. By adopting this, BDS Course regulations can also follow CBCS without neglecting or reducing the weightage of any subject. PMID- 27656466 TI - Factors Associated with Needlestick Injuries in Health Care Occupations: A Systematic Review. AB - INTRODUCTION: Needlestick and sharps injuries (NSIs), are among the main job related injuries that health care workers experience. In fact, contraction of hepatitis B or hepatitis C from work-related NSIs is one of the most common occupational hazards among health care workers. AIM: The aim of this study was to determine the factors associated with NSIs in health care occupation. MATERIALS AND METHODS: In this study, a systematic and purposive review with emphasis on the research question was run to retrieve, evaluate and consolidate the required information. The following four key words were used to search for the relevant articles published from January 1998 to May 2015: NSI health care workers, risk factor and factors associated, in Science direct, EBSCO Host, PubMed, ProQuest, SID and Cochrane Library. Several steps of evaluation were taken to select and analyse the full texts of relevant articles. According to the inclusion criteria, we finally selected 11 articles from the 18642 retrieved articles. RESULTS: The data of the analysed articles indicated that the highest incidence of NSIs was seen in nurses and that the associated factors were age, level of education, number of shifts per month and history of related training. The highest rate of NSIs was related to instrument preparation followed by injection and recapping of used needles. Findings show that health care workers suffer a high rate of needlestick injuries. CONCLUSION: It was seen that device, location, or action cannot be separately considered as responsible for all types of the NSIs. Rather, each of them has a contribution to the NSIs. Nevertheless, factors with higher frequency should be given a higher priority. PMID- 27656468 TI - Comparative Assessment of the Effects of Hatha Yoga and Physical Exercise on Biochemical Functions in Perimenopausal Women. AB - INTRODUCTION: Menopause is a transitional phase in which some women experience discomfort, while others may exhibit variety of symptoms. The power of yoga therapy in relieving stress, enhancing health, improving fitness and managing symptoms of a variety of disorders is remarkable. AIM: The current study was designed to study the effect of Hatha yoga therapy and regular physical exercise on the Fasting Blood Sugar (FBS), Glycated Haemoglobin (GHB), Thyroid Stimulating Hormone (TSH), serum cortisol and total plasma thiol levels in perimenopausal women. MATERIALS AND METHODS: The study included 216 women with perimenopausal symptoms, 111 in test group (Hatha yoga) and 105 in control group (physical exercise). The duration of intervention was 45 minutes every day for 12 weeks. Blood samples were collected in the pre and post intervention period. Statistical significance was defined as p<0.05. RESULTS: FBS and GHB (p<=0.05) showed a significant decrease after yoga therapy. Cortisol levels significantly (p<=0.05) increased in the post intervention period in the control group. However, it is maintained in the test group between the two time periods. The total plasma thiols level showed a rise in the post intervention period, significant rise (p<=0.001) in control group but not significant in the test group. The TSH levels were not altered in any group. CONCLUSION: It is concluded that exercise helps in maintaining the sugar levels but calming effects of yoga practice is important in relieving stress and enhancing health in perimenopausal women. PMID- 27656469 TI - Retention and Treatment Outcomes of an Undernutrition Program for HIV patients involving Ready-to-Use Therapeutic Food at Gondar University Hospital, Ethiopia: A Cross-Sectional Study. AB - INTRODUCTION: Despite global efforts to eradicate poverty and hunger, under nutrition is still a major health problem, especially in Sub-Saharan Africa, where HIV/AIDS prevalence is also a serious burden. AIM: To assess the retention and outcomes of under-nutrition treatment program in Gondar University Hospital, Ethiopia. SETTINGS AND DESIGN: A cross-sectional study was conducted in HIV positive children and adults participating in the Ready-to-use Therapeutic Food (RUTF) treatment program at Gondar University Hospital ART clinic for one year from November 2012 to November 2013. MATERIALS AND METHODS: Six hundred and thirty six patient records were followed-up for one year. Outcome variables were Mid-Upper Arm Circumference (MUAC) values measured as severe, moderate acute malnutrition, normal after treatment, non-respondent, relapsed and lost to follow up using the hospital records of HIV positive children and adults eligible for the program. STATISTICAL ANALYSIS: Univariate and multivariate analysis were performed to compute Crude Odds Ratio (COR) and Adjusted Odds Ratio (AOR). Statistical significance was set at p-value<0.05. RESULTS: Among 636 clients, 44.2% achieved MUAC measures >= 125 mm for children and >= 21 cm for adults at 4 and 6 months. 70.1% of those were children while 29.9% of the 281 were adults. Moreover, a more positive initial response to ready-to-use therapeutic food was found among children as there was significant increase (p<0.05) in MUAC value after the second month of initiating treatment while adults achieved a significant (p<0.05, p<0.01) in MUAC at the 4(th) and 6(th) month respectively. There was a significant association between age, nutrition status and treatment outcome, while sex, HIV status, education and residency were not associated with treatment outcome. CONCLUSION: Recovery and weight gain rates were below 50%. Defaulter rates were higher than the Sphere standards and recovery was better in children than adults. Integrated RUTF and HIV program and strict follow-up and education or counselling of HIV positive patients should be strengthened. PMID- 27656470 TI - Knowledge of Radiation Hazards, Radiation Protection Practices and Clinical Profile of Health Workers in a Teaching Hospital in Northern Nigeria. AB - INTRODUCTION: Use of ionizing radiation in medical imaging for diagnostic and interventional purposes has risen dramatically in recent years with a concomitant increase in exposure of patients and health workers to radiation hazards. AIM: To assess the knowledge of radiation hazards, radiation protection practices and clinical profile of health workers in UDUTH, Sokoto, Nigeria. MATERIALS AND METHODS: A cross-sectional study was conducted among 110 Radiology, Radiotherapy and Dentistry staff selected by universal sampling technique. The study comprised of administration of standardized semi-structured pre-tested questionnaire (to obtain information on socio-demographic characteristics, knowledge of radiation hazards, and radiation protection practices of participants), clinical assessment (comprising of chest X-ray, abdominal ultrasound and laboratory investigation on hematological parameters), and evaluation of radiation exposure of participants (extracted from existing hospital records on their radiation exposure status). RESULTS: The participants were aged 20 to 65 years (mean = 34.04 +/- 8.83), most of them were males (67.3%) and married (65.7%). Sixty five (59.1%) had good knowledge of radiation hazards, 58 (52.7%) had good knowledge of Personal Protective Devices (PPDs), less than a third, 30 (27.3%) consistently wore dosimeter, and very few (10.9% and below) consistently wore the various PPDs at work. The average annual radiation exposure over a 4 year period ranged from 0.0475mSv to 1.8725mSv. Only 1 (1.2%) of 86 participants had abnormal chest X-ray findings, 8 (9.4%) of 85 participants had abnormal abdominal ultrasound findings; while 17 (15.5%) and 11 (10.0%) of 110 participants had anemia and leucopenia respectively. CONCLUSION: This study demonstrated poor radiation protection practices despite good knowledge of radiation hazards among the participants, but radiation exposure and prevalence of abnormal clinical conditions were found to be low. Periodic in-service training and monitoring on radiation safety was suggested. PMID- 27656472 TI - Estimation of Noise Induced Hearing Loss (NIHL) with Hearing Deterioration Index (HDI). PMID- 27656471 TI - Endoscopic Repair of CSF Fistulae: A Ten Year Experience. AB - INTRODUCTION: Cerebrospinal Fluid (CFF) fistulae are repaired endoscopically with varying degrees of success around the world. Large series are still uncommon, and the results varied primarily because of the different techniques by different surgeons and also because of a variation in the patient profile in each series, for example, many series deal primarily with traumatic CSF leaks where the defects are larger and outcomes poorer. AIM: To analyse the surgical outcomes of Endoscopic CSF rhinorrhea closure. MATERIALS AND METHODS: This is a series of 34 cases operated upon primarily by one surgeon in two different centres over a period of 10 years. RESULTS: Of the 34 cases, 76% of the patients were women. Among the patients only 20.6% patients had a history of trauma preceding the CSF leak. The most common site of leak was in the fovea ethmoidalis in 19 (55.8%) followed by 10 (29.4%) in the cribriform plate. An overlay technique of placing the multiple layers of fascia and mucosa was used in 26 (76.5%) patients and underlay technique in the remaining. Postoperative lumbar drain was used in all patients. CONCLUSION: Based on the treatment outcome of the 34 patients, it can be concluded that the success rate of a single endoscopic procedure in our experience is 97% and 100% following the second. Endoscopic approach for closure of CSF leak is safe with minimal complications and little morbidity. PMID- 27656475 TI - Retinal Pigment Epithelial Tear Developing in a Patient with Outer Retinal Tubulations: Pathogenic Association or Coincidence? PMID- 27656474 TI - A Rare Variation of the Axillary Nerve Formed as Direct Branch of the Upper Trunk. AB - The brachial plexus has a complex anatomical structure from its origin in the neck and through its course in the axillary region. Knowledge of variations of the brachial plexus has important clinical applications especially in relation to trauma and surgical procedures of upper limb. The present study has reported a rare variation of the brachial plexus where the "axillary nerve" arising as a direct branch from the upper trunk instead from the posterior cord. Once the "axillary nerve" was given off, the remaining superior trunk had joined with the anterior division of middle trunk in the formation of the lateral cord. The posterior cord was formed by the union of posterior divisions of the middle and inferior trunks. The "axillary nerve" has given off braches to subscapularis, latissimus dorsi, deltoid and teres minor muscles while having given a "communicating branch" for the posterior cord. The current report indicates an anatomical variation not documented so far which may help in planning safe surgical procedures in this region and to explain unusual resulting complications. PMID- 27656473 TI - Total Upper Eyelid Reconstruction with Modified Cutler-Beard Procedure Using Autogenous Auricular Cartilage. AB - INTRODUCTION: Malignant tumour in upper lid is a surgical challenge to oculoplastic surgeon. Full thickness defect created after removal of large tumour promptly treated with modified cutler beard procedure using autogenous auricular cartilage. Surgical procedure is two staged: In first stage, removal of the tumour followed by full thickness flap repaired; In second stage, opening the closed lid with lid margin repair. Post-operatively, there is good anatomical, functional and cosmetic restoration of the eyelid similar to the other eye. AIM: To evaluate the efficacy of the modified Cutler-Beard procedure using autogenous ear cartilage for tarsal plate reconstruction in the repair of 70-100% upper eyelid defects. MATERIALS AND METHODS: This is a prospective, interventional case series of 16 patients over a period of three years. Patients with upper eyelid defects, secondary to removal of tumour, greater than or equal to 70% were included. Of these patients, those with lymph node involvement, distant metastasis, lower eyelid involvement, corneal infiltration or intra-orbital extension were excluded. FNAC was done in all the cases. Created defect was measured in mm (length and width) and later expressed in percentage. Pre and Post operative measurement of Levator Palpebrae Superioris (LPS) was done. Pre and Post-operative measurement of Margin to Reflex Distance (MRD1) were also noted. RESULTS: Upper eyelid recreation was successful in all patients without complications. Pre-operative LPS action ranged from 0-4 mm, while post-operative LPS action was 12-14 mm. Pre-operative MRD1 ranged from -4 millimeters to -1 mm, while post-operative MRD1 was +3 to +4 millimeters. The follow-up period ranged from six months to two years. Every patient had a successful upper eyelid reconstruction. CONCLUSION: The modified Cutler-Beard procedure using an autogenous auricular cartilage graft is an effective procedure for repair of large upper eyelid defects, with acceptable functional and cosmetic results. Furthermore, it is particularly useful in resource-poor areas, due to lower cost than other available options. PMID- 27656476 TI - A Clinical Study of Acute Kidney Injury in Tropical Acute Febrile Illness. AB - INTRODUCTION: Tropical Acute Febrile Illness (TAFI) is one of the most common causes of morbidity within the community. Acute Kidney Injury (AKI) due to infective and non infective causes is a major complication. Presence of AKI is a major cause of mortality among patients with TAFI. AIM: To study the spectrum of tropical acute febrile illness; the proportion, spectrum and staging of acute kidney injury; Renal Replacement Therapy (RRT) initiation and in-hospital mortality. MATERIALS AND METHODS: A total of 600 TAFI patients were prospectively studied at a tertiary care centre in coastal Karnataka between September 2012 and September 2014 for the aetiology of TAFI; the development and staging of AKI based on Kidney disease: Improving global outcomes (KDIGO) guidelines; the initiation of RRT and in-hospital mortality. STATISTICAL ANALYSIS: Data analysis was done using SPSS version 17.0 with statistical significance calculated using chi-square and Fisher's exact t-test for which p-value <0.05 was considered significant. RESULTS: The spectrum of TAFI, in decreasing order, was vivax malaria, leptospirosis, dengue fever, falciparum malaria, mixed malaria, enteric fever, scrub typhus and the most common aetiology was malaria. The proportion of AKI was 54%. The most common cause of AKI, its stages 2 and 3, RRT initiation and in-hospital mortality was leptospirosis; and AKI stage 1 was dengue fever. KDIGO AKI stage 1, 2 and 3 was seen in 46.9%, 31.2% and 21.9% of AKI patients, respectively. RRT initiation was required in 10.2% of AKI patients and in hospital mortality was 3% among all patients. AKI, RRT initiationand in-hospital mortality were significantly associated with older age, fever duration and other presenting complaints, examination findings, renal function and other parameters, leptospirosis, dengue fever, falciparum malaria. CONCLUSION: The aetiology in about half of TAFI patients in coastal Karnataka was malaria. More than 50% develop AKI with greater than one-fifth of them progressing to AKI stage 3 and one-tenth requiring RRT. The most common cause of AKI, AKI stage 2, 3, RRT initiation and in-hospital mortality was leptospirosis. AKI was present in almost all patients with leptospirosis. Therefore leptospirosis was the most nephrotoxic acute febrile illness in the present study population. Dengue fever was the most common cause of AKI stage 1. Vivax malaria was the third most common cause of AKI. The factors like age, presenting complaints, examination findings, renal function and other parameters, aetiology and RRT initiation may be used to predict AKI and in-hospital mortality. PMID- 27656477 TI - Comparison of Oral Montelukast and Intranasal Fluticasone in Patients with Asthma and Allergic Rhinitis. AB - INTRODUCTION: Even though the links between upper and lower airway had been of interest to clinicians since long back, it has not attracted the attention of the researchers till recent past. But the evidence is still far from conclusive, due to limited number of randomized controlled trials available on subjects with concomitant allergic rhinitis and asthma. This gap in the knowledge is even more conspicuous in Indian population. AIM: The current study is conducted with an objective of comparing the efficacy and tolerability of intranasal Fluticasone and oral Montelukast in treatment of allergic rhinitis and bronchial asthma. MATERIALS AND METHODS: The study was a prospective randomized, single blinded, comparative, parallel group study, with two intervention groups conducted in a tertiary teaching hospital in Chennai, Southern India. One hundred and twenty patients diagnosed with concomitant diagnosis of allergic rhinitis and bronchial asthma was randomly allocated to either Fluticasone propionate aqueous nasal spray or oral Montelukast group. RESULTS: Out of total 120 subjects recruited, 108 subjects were included in the final analysis. The mean reduction in asthma and rhinitis symptom scores and improvement in PEFR was higher for Group A, compared to Group B during all the follow-up periods. No statistically significant difference was observed in proportion of subjects reporting exacerbations in the current study. Both the treatments were well tolerated. CONCLUSION: Addition of intranasal Fluticasone propionate to Salmeterol plus Fluticasone is beneficial in improving asthma control, allergic rhinitis control and lung functions as compared to oral Montelukast. Thereby the use of intranasal Fluticasone Propionate in comparison to oral Montelukast in control of Allergic Rhinitis is justified as per the significant improvement in outcome measures. PMID- 27656478 TI - Efficacy of Zinc Sulfate in Peptic Ulcer Disease: A Randomized Double-Blind Clinical Trial Study. AB - INTRODUCTION: Peptic ulcer is a common disease that affects millions of people worldwide. Considering its global prevalence finding new approach for treating is important. AIM: The aim of this study was to investigate the effect of zinc sulfate on gastric and duodenal ulcer treatment. MATERIALS AND METHODS: This double-blind clinical trial study was done on 90 patients who were admitted to the gastrointestinal endoscopy clinic of Tohid hospital in Sanandaj, Iran. All patients were diagnosed with gastric and duodenal ulcers. They were randomly divided into two-intervention and control groups, using block randomization with block sizes of 4. Patients and researcher were unaware of the grouping. To assess the level of zinc, blood samples were taken. In case of positive Rapid Urease Test (RUT), triple therapy regimen including amoxicillin, clarithromycin and omeprazole was administered for two weeks. For intervention group in addition to "triple therapy", an oral dose of Zinc Sulfate 220mg capsules were administered daily, while the control group received placebo capsules. RESULTS: A total of 54.5% and 57% of the patients in the intervention and control groups had gastric ulcer respectively. The Rapid Urease Test (RUT) result of 72.7% of intervention group and 83.3% of control group was positive (p = 0.24). Serum zinc level of 20.9% of intervention group and 35.7% of control group was lower than the normal level (p = 0.13). The mean of serum zinc level of intervention group and control group were 81.9 and 78.9 mg dL respectively (p = 0.4). After intervention, peptic ulcer in 81.8% of the intervention group and 83.3% of the control groups were improved (p= 0.85). Response to treatment were higher in patients with normal zinc levels compared to patients with abnormal levels (77.5% vs. 22.5%, p=0.019). CONCLUSION: A daily dose of 220mg zinc sulfate was not significantly effective on peptic ulcer. However, patients with normal zinc levels had better ulcer treatment. PMID- 27656479 TI - Study of Aetiology and Outcome in Acute Febrile Illness Patients with Multiple Organ Dysfunction Syndrome. AB - INTRODUCTION: Acute febrile illness with Multi Organ Dysfunction Syndrome (MODS) carries significant morbidity and mortality despite standard therapy in intensive care settings. Infections are the most common cause of MODS followed by polytrauma. Present study was undertaken in medical intensive care units of a tertiary hospital to study the aetiology and outcome among patients with acute febrile illness developing MODS. AIM: 1) To study the aetiology of acute febrile illness in patients developing MODS. 2) To study the final outcome among these patients. MATERIALS AND METHODS: The present study was conducted at a tertiary care hospital in Mysuru, Karnataka, India, over a period of 6 months from July 2013 to December 2013. The Institutional Ethics Committee Approval (IEC) was obtained before the commencement of the study. A total of 213 cases admitted in intensive care unit with acute febrile illness with two or more organ dysfunction were screened for the inclusion and exclusion criterias. RESULTS: A total of 213 cases of acute febrile illness with one or more organ dysfunction were screened. Of the screened patients 75 patients were finally included in the study out of which 46 (61.3%) patients were males and 29 (38.7%) patients were females. Aetiology for acute febrile illness with MODS could be established in 49 (65.3%) patients and it was obscure in 26 (34.7%) patients despite repeated investigations. Dengue infection (29.3%) was the commonest cause of febrile illness with MODS followed by leptospirosis (22.7%). Majority of these patients had haematological derangements (78.7%) and liver function test abnormalities (68%). Out of these 75 cases, 54 (72%) patients recovered completely and 21 (28%) patients died. Among males (N=46), 35 (76.1%) patients recovered and 11 (23.9%) patients died where as among females (N=29), 19 (65.5%) patients recovered and 10 (34.5%) patients died. Mortality was proportionate with the number of organ dysfunction, especially Central Nervous System (CNS) involvement. CONCLUSION: Incidence of febrile illness with MODS is more prevalent in males but the outcome appears poorer among females. The diagnosis remained obscure in a sizable proportion of these patients. Prognosis was inversely dependent on the number of organs involved especially with CNS manifestations. PMID- 27656480 TI - Comparative Effect of Insulin Sensitizers and Statin on Metabolic Profile and Ultrasonographical Score in Non Alcoholic Fatty Liver Disease. AB - INTRODUCTION: Non Alcoholic Fatty Liver Disease (NAFLD) is a metabolic disorder involving fat accumulation in the liver. The initial management for patients with NAFLD includes lifestyle modification and weight loss in overweight or obese patients. AIM: The present study was conducted to compare the efficacy of insulin sensitizers and statin in the patients of NAFLD. MATERIALS AND METHODS: The study included 98 patients diagnosed with NAFLD on USG (Ultrasonography) abdomen, divided into three Groups randomly and administered Metformin (Group I), Rosuvastatin (Group II) or Pioglitazone (Group III) along with dietary intervention and lifestyle modification. Their Body Mass Index (BMI), liver function tests, fasting lipid profile, USG scores for fatty liver were done and followed up at 4 weeks, 12 weeks and 24 week for change in above parameters. RESULTS: Out of the three Groups, Group II showed a maximum improvements in usg scores for NAFLD (p<0.001) and fasting lipid profile. Group II also showed maximum derangement of liver enzymes at 24 weeks though none of the subjects had more than three times elevation of liver enzymes. CONCLUSION: Rosuvastatin may be an effective therapy as add on treatment to dietary and lifestyle intervention in patients of NAFLD. As an add-on treatment Rosuvastatin was superior to Pioglitazone or Metformin and acute decompensation is unlikely with this drug. Metformin was not effective as add on therapy for NAFLD, rather rapid weight loss in short period of time resulted in worsening of hepatic steatosis. PMID- 27656481 TI - Effect of Vitamin D on Anginal Episodes in Vitamin D Deficient Patients with Chronic Stable Angina on Medical Management. AB - INTRODUCTION: Vitamin D deficiency has been found to contribute to various cardiac conditions, such as hypertension, coronary artery disease, stroke, and atherosclerosis. However, the clinical cardiovascular benefits after short term supplementation have not been reported. AIM: To study the beneficial effect of Vitamin D supplementation on angina episodes in Vitamin D deficient patients with chronic stable angina on medical management. MATERIALS AND METHODS: A total of 40 patients were studied with group 1 (20 patients) with low Vitamin D levels and group 2 with normal Vitamin D levels. 60000 IU of Vitamin D supplementation was given every week for 8 weeks in group 1. Frequency of anginal episodes and use of sub-lingual nitrates were compared at base-line and after 8 weeks post supplementation. RESULTS: Significant 20% (p <0.05) reduction in anginal episodes and 17.24% (p <0.05) reduction in use of sub-lingual nitrates was noted in group1 after Vitamin D supplementation. The benefits were independent of BP, heart rate and medications, thus, attributing to supplementation. No significant change was noted in group 2. CONCLUSION: Cardiovascular patients need to be evaluated for Vitamin D deficiency. Supplementation to correct Vitamin D levels may have additional cardiovascular benefits like reduction in angina episodes. PMID- 27656482 TI - Correlation between 2D Echocardiography and Multidetector Row CT for Early Detection of Diastolic Dysfunction in Normotensive Diabetic Patients. AB - INTRODUCTION: Abnormalities in diastolic function are considered early signs of diabetic cardiomyopathy. Two dimensional echocardiography with Tissue Doppler Imaging (TDI) has been used most commonly to evaluate diastolic left ventricular function. AIM: The study was conducted to study the prevalence of diastolic dysfunction with the help of echocardiography and MDCT and their correlation in asymptomatic diabetic people. MATERIALS AND METHODS: A total of 15 diabetic, normotensive patients who had undergone 64-multidetector row CT and 2D echocardiography with TDI were included. The parameters used for assessment of diastolic dysfunction were early (E) and late (A) transmitral peak velocity (cm/s) and peak mitral septal tissue velocity (Ea; cm/s). Subsequently, LV filling pressures (E/Ea) were estimated. RESULTS: Of the total 73.3% patients showed presence of diastolic dysfunction by both CT and echocardiography. Good correlations were observed between cardiac CT and 2D echocardiography for assessment of E (r = 0.992; p < 0.001), A (r=0.974, p <0.001), E/A (r = 0.979; p < 0.01), Ea (r = 0.977; p < 0.001), and E/Ea (r = 0.994; p < 0.001). CONCLUSION: Doppler echocardiography is considered one of the best methods for assessment of LV diastolic dysfunction. In this study of cardiac-asymptomatic diabetic patients, MDCT and echocardiography showed good correlation for assessment of early diastolic dysfunction. Hence, cardiac CT can be an additional tool for assessing LV diastolic function. PMID- 27656483 TI - Study of Hepatic Osteodystrophy in Patients with Chronic Liver Disease. AB - INTRODUCTION: Chronic Liver Disease (CLD) is a major cause of morbidity and mortality worldwide. It involves haemodynamic and metabolic complications. Hepatic Osteodystrophy is a metabolic bone disease that may occur in individuals with chronic liver disease. It can significantly affect morbidity and quality of life of these patients. Fractures are also associated with an excess mortality. It has been an under recognized and inadequately studied complication among Indian population. An early diagnosis is essential to correct reversible risk factors which predispose to bone mass loss. AIM: To assess the prevalence of metabolic bone disease and identify the risk factors associated with hepatic osteodystrophy in patients with cirrhosis. MATERIALS AND METHODS: This was an observational, cross-sectional, hospital based study conducted at a medical college hospital. All patients more than 20-year-old, diagnosed with chronic liver disease/Cirrhosis were enrolled. They were subjected to haematological, biochemical investigations, evaluation of Vitamin D and other hormonal parameters. Bone Mineral Density (BMD) was estimated by Dual Energy X-ray Absorptiometry (DEXA). RESULTS: A total of 72 patients with mean age 50.04+/ 11.24 years were included in the study. Amongst causes of chronic liver disease were alcoholic liver disease 22 (30.6%), CLD due to hepatitis B 24 (33.3%) and chronic hepatitis C 26 (36.1%). Twenty one (29.2%) patients had normal BMD while 51 (70.8%) had a low BMD. Out of these 51 patients, 36 (70.6%) were diagnosed of osteopenia and 15 (29.4%) others were found to have osteoporosis. Vitamin D levels and severity of liver disease had correlation with low BMD. CONCLUSION: Low BMD is highly prevalent in patients with chronic liver disease of variable aetiologies. We advocate more randomised and prospective studies to be conducted on homogeneous groups with chronic liver disease in its various stages. In view of numerous therapeutic options available both for liver disease and bone disease, it is prudent to characterize this condition in order to give these patients a better chance of survival with good quality of life. PMID- 27656484 TI - Markers of Oxidative Stress and Clinical Outcome in Critically ill Septic Patients: A Preliminary Study from North India. AB - INTRODUCTION: Sepsis is the leading cause of mortality in non-coronary Intensive Care Units (ICUs). Oxidative stress is one of the important features in pathogenesis of sepsis. AIM: This study was undertaken to evaluate levels of oxidants and antioxidants in patients with sepsis admitted to ICU. STUDY DESIGN: This was a non-interventional clinical case-control study undertaken at a tertiary level teaching hospital in New Delhi, India. MATERIALS AND METHODS: Forty-six consecutive non-pediatric patients admitted to ICU with sepsis were included and subjected to detailed history, physical examination and investigations. Blood samples were drawn to evaluate oxidant Malondialdehyde (MDA) and antioxidant (alpha-tocopherol) levels. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Organ Dysfunction and/or Infection (ODIN) scores were calculated and patients followed up for outcomes. Twenty age and sex matched healthy subjects served as controls. RESULTS: Mean levels of malondialdehyde were higher in patients than controls (17.2+/-3.8nm/ml versus 4.6+/-1.6nm/ml, p<0.001) while levels of alpha-tocopherol were lower (3.2+/ 1.3MUg/ml versus 9.9+/-2.0MUg/ml, p<0.001). The mean APACHE II and ODIN scores were 18.1+/-9.3 and 1.7+/-1.3 respectively in patients. These scores were two to three fold higher in non survivor patients (n=22) in comparison with survivors (n=18) (p<0.001). There was no significant difference between the two groups in oxidants and antioxidants levels (p>0.05). However, a significant and positive correlation was observed between oxidant -antioxidant levels and APACHE II, ODIN and International Normalized Ratio (INR) scores in septic patients overall. CONCLUSION: The oxidants in septic patients were significantly higher while antioxidants were significantly lower than healthy controls. There was also a significant correlation with APACHE II and ODIN scores. A large patient population based study may draw more specific conclusions. PMID- 27656485 TI - Post Exposure Prophylaxis for Occupational Exposures to HIV and Hepatitis B: Our Experience of Thirteen Years at a Rural Based Tertiary Care Teaching Hospital of Western India. AB - INTRODUCTION: Health Care Workers (HCWs) are at risk of occupational transmission of HIV, Hepatitis B and Hepatitis C, which can be minimized by following guidelines for standard precautions as well as taking Post Exposure Prophylaxis (PEP) measures. There are limited studies from India documenting details of PEP for HIV and Hepatitis B. AIM: We aimed to study the efficacy, tolerance, details of PEP regimens used among HCWs exposed to HIV and Hepatitis B as well as vaccination status and (Anti-Hepatitis B Surface Antigen) anti-HBS Antibody Titre Level Among HCWs exposed Hepatitis B. STUDY DESIGN: This retrospective observational study was done at a rural based tertiary care teaching centre of Western India. MATERIALS AND METHODS: Hospital Infection Control Committee of our institute was maintaining a record of all reported incidences of HIV and Hepatitis B positive exposures since 2003. We analysed reported incidences of exposures to HIV and Hepatitis B positive source occurred during the period of January 2003 to December 2015. RESULTS: Of the total 96 exposures, 48 were to HIV and 48 were to Hepatitis B. Of the 48 exposures to HIV, PEP was warranted in 39. Of 39 exposures, only 14 (35.9%) received PEP within two hours. Basic regimen was used in 22 and expanded in 17 exposures. Only 12 (31.6%) reported side effects to PEP. Zidovudine based regimen was less well tolerated. All side effects were reported by female HCWs only. Of the 48 exposed to Hepatitis B, 33 (68.6%) were completely vaccinated. Out of 33, titre result was not available for eight. Three (12.0%) of remaining 25 were having low titre (<10mIU/ml) of anti-HBS antibody. Five of six with incomplete vaccination status demonstrated anti HBS antibody titre > 100mIU/ml. Of the 48, in 17 (35.4%) incidences no action was required; 23 (47.9%) were managed with booster dose of Hepatitis B vaccine and eight (16.7%) with Hepatitis B immunoglobulin. No cases of sero-conversion was reported either for HIV or Hepatitis B from available data. CONCLUSION: Inspite of high incidences of exposures to HIV or Hepatitis B positive source, good efficacy of PEP was observed with no sero-conversion. PEP for HIV was well tolerated; female HCWs were less tolerant. Study emphasized the need for creating awareness about timely reporting of incidence, achieving maximum vaccination against Hepatitis B for all HCWs and need for anti-HBS antibody titre. PMID- 27656486 TI - Transient Ischemic Attack Versus Seizure: Use of Complete Blood Count Parameters for Differential Diagnosis. AB - INTRODUCTION: Seizures are an important group of diagnoses in the differential evaluation of Transient Ischemic Attack (TIA)because of their variable and temporary signs and symptoms. Physicians must frequently rule out TIA in asymptomatic patients with normal diagnostic neuroimaging. AIM: The current study aimed to investigate the efficacy of Complete Blood Count (CBC) components in the differential diagnosis of TIA and seizures. MATERIALS AND METHODS: Our study was a retrospective case-control study. Patients admitted to the Emergency Department (ED) and hospitalized with an initial diagnosis of TIA or seizure at the neurology clinic of Erzurum Ataturk University Training Hospital between January 1, 2012, and December 31, 2014, were recruited for the study. Patients with inaccessible or missing data were excluded. RESULTS: We identified 1,459 ED admissions that resulted in neurology clinic hospitalizations of patients with initial diagnoses of TIA (n=911) and seizure (n=420) over a 24-month time period. A total of 128 patients were excluded from the study. CONCLUSION: We conclude that CBC may have a diagnostic value on TIA and seizure differentiation, but this is limited because of statistical and clinical incompatibility. Elevated White Blood Cells (WBC) values of seizure patients compared with TIA patients' may help clinicians at the preliminary phase of diagnostic studies. We conclude that age is a remarkable and valuable demographic parameter in addition to physical examination, laboratory and imaging studies. PMID- 27656487 TI - Insulinoma Causing Prolonged Hypoglycaemic Coma. AB - Insulinoma is a rare pancreatic endocrine tumour with an incidence of four cases per million per year. A recurrent episode of fasting hypoglycaemia is the most common manifestation of these tumours. Diagnosis is often delayed due to varied presentation but once diagnosed, prognosis is often good after surgical resection of the lesion. Severe hypoglycaemia in insulinoma causing coma and death is rare. We report a case of hypoglycaemic coma secondary to an insulinoma in an elderly man which proved fatal. PMID- 27656488 TI - Percutaneous Coronary Intervention of Hidden Coronary Artery-Unusual Type of Isolated Single Coronary Artery. AB - Single coronary artery is a rare congenital coronary artery anomaly, the incidence of which is 0.024-0.066% as described in literature. Report of cases having single coronary artery along with acute myocardial infarction are scanty and reports of percutaneous intervention in such a situation are even fewer, technically challenging and potentially cataclysmic. As single coronary artery supplies the entire myocardium, occlusion of this can result in significant ischemic insult, resulting in severe biventricular dysfunction. Percutaneous Coronary Intervention (PCI) of single coronary artery is technically challenging and carries high risk which may be equated to left main intervention. We report a rare interesting case of L1 variety of single coronary artery which presented as acute inferoposterior myocardial infarction with successful rescue PCI to Left Circumflex Artery (LCx). PMID- 27656489 TI - Rare Offshoot of a Common Malady Anaemia and Tuberculosis. AB - Haematological manifestations are one of the rarer presentations of tuberculosis and are usually of normocytic normochromic type. An association of Autoimmune Haemolytic Anaemia (AIHA) with active pulmonary tuberculosis is an exceeding rare entity, though anaemia and tuberculosis commonly co-exist. We report a patient with sputum negative pulmonary tuberculosis with associated Coomb's positive AIHA. The patient responded well to Anti- Tubercular Therapy (ATT) and low dose steroids tapered over a month. PMID- 27656490 TI - Endobronchial Inflammatory Myofibroblastic Tumour-A Case Report. AB - Lung malignancies are on the rise and sadly present at an advanced stage. Fiberoptic bronchoscopy is used for staging as well as in diagnosis of lung malignancies. However, not all endobronchial growth are malignant. Inflammatory Myofibroblastic Tumour (IMT) is one of the rare tumours of the lung. A controversy regarding the benign versus malignant nature of the tumour is still ongoing. The management of these tumours can be challenging because there are no established treatment protocols. Although IMT most commonly arises from lung, endobronchial presentation is very rare. We report a case of endobronchial presentation of IMT and discuss about its aetiology and treatment options. PMID- 27656491 TI - Cefoperazone Induced Gastrointestinal Bleeding. AB - Cefoperazone is a beta-lactam antibiotic which is frequently used in treating a variety of gram positive and gram negative infections. The chemical structure of cefoperazone contains a side chain of N-methylthiotetrazole which can inhibit vitamin K metabolism resulting in hypoprothombinemia. We report a case of cefoperazone induced coagulopathy manifesting as gastrointestinal bleeding. A Naranjo assessment score of 5 was obtained, indicating a probable relationship between the patient's coagulation function disorder and her use of the suspect drug. PMID- 27656492 TI - Vascular Disease in Young Indians (20-40 years): Role of Hypertension. AB - Hypertension (HTN) being one of the important risk factors for cardiovascular disease (CVD) is a significant health concern, especially in India. With age, prevalence of HTN, especially systolic HTN increases. Special attention needs to be directed to HTN in young ages (20-40 years) due to lower awareness, need for early treatment and better control of HTN. HTN in the age group of 20-40 years needs critical reappraisal. Given the high prevalence of HTN in the general population in India, in this review we attempt to provide current evidence and expert opinion on epidemiology, aetiopathogenesis and treatment of HTN in young (20-40 years) Indians. PMID- 27656495 TI - Pneumothorax Ex Vacuo Following Chemotherapy for Malignant Pleural Effusion. PMID- 27656494 TI - Where is the Blood Leaking From? PMID- 27656496 TI - Meningotheliomatosis: A Rare Cause of Diffuse Miliary Pattern Pulmonary Opacities. PMID- 27656493 TI - Vitamin Supplementation as an Adjuvant Treatment for Alzheimer's Disease. AB - Alzheimer's Disease (AD) is a slowly progressing neurodegenerative disorder representing a major health concern worldwide. This disorder is characterised by progressive dementia and cognitive decline. The pathological hallmarks of AD include the presence of Abeta plaques and tau neurofibrils. Research has shown that oxidative stress represents a major risk factor associated with AD pathology. Accumulation of Abeta plaques and relative lack of antioxidant defence mechanisms, including cellular antioxidant enzymes and dietary antioxidants like vitamins, assist in the exacerbation of oxidative stress. Reactive Oxygen Species (ROS) produced as the result of oxidative stress, that increase structural and functional abnormalities in brain neurons, which then manifests as dementia and decline in cognition. Data from numerous epidemiological studies suggests that nutrition is one of the most important yet modifiable risk factors for AD. Since oxidative stress contributes a great deal in the development and progression of AD, anything that could attenuate oxidative stress would help in decreasing the prevalence and incidence of AD. There is increasing evidence that supports the use of different antioxidant as an adjuvant treatment for AD. Vitamins are one such antioxidant that can be used as an adjuvant in AD treatment. This paper will focus on the evidence, based on current literature, linking the use of vitamin supplementations as an adjuvant treatment for AD. PMID- 27656498 TI - The Laparoscopic Re-Exploration in the Management of the Gallbladder Remnant and the Cystic Duct Stump Calculi. AB - INTRODUCTION: The gallbladder remnant and the cystic duct stump calculi are uncommon causes of post-cholecystectomy syndrome. Re-exploration is usually needed in the cases where symptom persists. Very few case series and reports are available regarding laparoscopic re-exploration. AIM: To assess the safety and feasibility of Laparoscopic re-exploration in the cases of gallbladder remnant and cystic duct stump calculi leading to post cholecystectomy syndromes. MATERIALS AND METHODS: In this study, laparoscopic re-explorations was done in 22 patients in which 17 patients had gallbladder remnant calculi and 5 had cystic duct stump calculi. The study considered parameters like the operative time, conversion rate, post-operative complications, post-operative hospital stay and mortality in these patients. The duration of study was 15 years and the data was retrospectively reviewed. RESULTS: The median operating time was 83 minutes (range 51 to 134 minutes). Only one patient had conversion to open surgery. In postoperative period two patients had bile leak. They were managed conservatively and leak subsided in 8 and 11 days respectively. One patient had postoperative bleeding not requiring blood transfusion. There was no major complication requiring further intervention and no mortality. Patients were discharged on median day 4 (range 2-11) after the surgery. Patients were followed up every 3 months for one year. However, out of these three patients did not turn up for follow-up. CONCLUSION: In expert hands laparoscopic re-exploration of the gallbladder remnant/cystic duct stump calculi can be performed within a reasonable operating time. The conversion to conventional re-exploration rate was very low with minimal post-operative complications and shorter hospital stay. PMID- 27656497 TI - Fertility Potential in Adult Hypospadias. AB - INTRODUCTION: Hypospadias is a congenital anomaly of the urogenital tract characterized by abnormal location of the external urethral meatus over ventral aspect of penis. The ideal time to correct primary hypospadias is when aged 6-12 months. However, in some developing countries, such as ours, this anomaly may be left untreated until adulthood. There are multiple risk factors responsible for development of this anomaly, out of which paternal sub fertility is one of them. As the child grows into adulthood, fertility status becomes an important issue, frequently raised by patients. AIM: To evaluate the fertility potential of adult hypospadiac patients and to rule out the effect of age of surgical correction over fertility potential. MATERIALS AND METHODS: Seventy three adult patients of hypospadias were prospectively evaluated, out of which 43 were operated during adulthood. All patients underwent measurement of penile length and circumference in both flaccid and erect positions along with testicular volume, serum LH, FSH and testosterone and semen analysis. A set of questionnaire was given to all the patients which included assessment of erectile function (IIEF-5), ejaculatory function, strength of libido and level of satisfaction after sexual intercourse. Results were compared with an age matched control group of 70 healthy person. RESULTS: Out of 73 patients with a mean age of 23.73 years, 14(19.17%) had proximal and rest 59(80.82%) had distal type of hypospadias. Mean penile length in both type of hypospadiac patients under both flaccid and erect conditions (7.92+/-1.33 and 9.62+/-1.31cm) were significantly shorter than those of control (10.78+/-0.94 and 13.15+/-1.15 cm) (p<0.001). In spite of short penile length, the level of satisfaction of all patients and their partner after penetrating intercourse were comparable to control (p>0.05). The strength of libido (p>0.05) was comparable with control in both type of hypospadiac patients; however IIEF-5 scores was poor in the proximal type of hypospadias. Semen volume (ml), sperm concentration (mill/ml), active sperm motility (%), and normal sperm morphology were comparable between distal hypospadiac group and control (p>0.05), however these parameters were poor in proximal type. The serum FSH and LH levels were significantly higher and serum testosterone level was significantly lower in hypospadiac patients than control (p <0.001). However, no difference in testicular size was found. The patients who were operated during childhood had shorter penile length compared to patients operated during adulthood. CONCLUSION: Fertility potential parameters in distal type of hypospadias were comparable with control. However the proximal type had poor erectile function and semen quality. Patients operated in either childhood or in adulthood, there was no significant difference in fertility potential. PMID- 27656499 TI - Adrenal Schwannoma: A Rare Incidentaloma. AB - Adrenal schwannomas are very rare tumours that are difficult to diagnose preoperatively. A 42-year-old male presented with epigastric pain and indigestion. He had history of repeated operations for recurrent facial swelling on both sides of face diagnosed as Angiolymphoid Hyperplasia with Eosinophilia (ALHE). Physical examination revealed right facial swelling. Laboratory tests showed no evidence of hormonal hypersecretion. CECT abdomen showed a well-defined heterogenously enhancing right adrenal mass (5x4cm). Patient underwent right adrenalectomy. Histopathology revealed adrenal schwannoma, confirmed by immunohistochemistry (IHC) showing diffuse expression of S-100. Fine-needle aspiration biopsy of facial lesion confirmed ALHE recurrence. Less than 35 cases have been reported. Diagnosis of adrenal schwannoma on imaging studies is very difficult and surgical resection when performed for non-functioning adrenal masses >4cm clinches the diagnosis. Adrenal schwannoma is highly uncommon and was incidentally associated with recurrent ALHE. PMID- 27656500 TI - Bronchoesophageal Fistula Repair with Intercostal Muscle Flap Followed by Occlusion of Residual Diverticula with N-butyl Cyanoacrylate (NBCA) Glue: A Case Report. AB - The incidence of bronchoesophageal fistula in presence of benign pathology of tracheal tree or oesophagus is rare. It is encountered in thoracic diseases like tuberculosis, syphilis or histoplasmosis due to erosion by infected lymph node or abscess to adjoining structures. The source of primary pathology has to be eliminated followed by appropriate steps of fistula tract closure is essential for optimal result. We report a 25-year-old patient with left sided bronchoesophageal fistula. He had a past history of pulmonary tuberculosis. A left lower lobectomy followed by repair of oesophageal fistula opening was performed by primary closure and reinforcement with an intercostal muscle flap based on posterior intercostal artery. Postoperative oesophagogram showed short diverticula, which was occluded with n-butyl cyanoacrylate (NBCA) glue under radiological guidance. Feeding was started one week after application of glue without further complication. Reports on intercostals muscle flap repair and intervention of residual oesophageal diverticula with n-butyl cyanoacrylate (NBCA) glue under radiological guidance are scanty. PMID- 27656501 TI - Recurrent Left Atrial Myxoma in a Young Patient: A Rare Entity. AB - Recurrence of atrial myxoma arising from the site other than inter-atrial septum is quite rare, which is more common in familial than sporadic cases. We here in present a case of 15-year-old young female who presented with recurrence of left atrial (LA) myxoma from unusual site - posterior LA wall after 3 years without any constitutional symptoms, which is the hallmark of recurrence. Complete removal of underlying atrial septum with atrial wall for recurrence prevention is the dictum in primary operation for tumour removal. PMID- 27656503 TI - Schwannoma of Upper Lip: Report of a Rare Case in a Rare Age Group. AB - Schwannoma is a benign, encapsulated perineural tumour originating from the schwann cells of the neural sheath of peripheral motor and sensory nerves. It may develop at any age but is extremely rare in paediatric age group. The tumour is frequently located on the head and neck region, the tongue being the most common site followed by the palate, floor of mouth, buccal mucosa, lips and jaws. Schwannomas rarely occur in the lip area and it is exceedingly rare in the upper lip. The lesion is usually solitary but can be multiple when associated with neurofibromatosis. The diagnosis is usually confirmed after biopsy and anti-S100 protein immuno-histochemical staining is usually used to identify the tumour. In the present study the patient was a 14-year-old young girl with the schwannoma on the upper lip which is probably the third such case in a paediatric age group being reported and was excised without any recurrence at 2 year after excision. PMID- 27656502 TI - Congenital Defect in Lesser Omentum Leading to Internal Hernia in Adult: A Rare Case Report. AB - Intestinal obstruction is one of the common clinical condition which is encountered in emergency room. Internal hernia is one of the rare causes of small bowel obstruction accounting for less than 1% of cases. A congenital omental defect is very rare, but can potentially cause internal hernia leading to obstruction or strangulation of the bowel. We present a case of a 54-year-old man who was brought to the emergency department with sudden onset of lower abdominal pain. He had no history of abdominal surgeries or history of trauma. An emergency laparotomy was performed. On exploring the abdominal cavity, the lesser omental defect was detected, 3cm in size. Loops of jejunum had gone through the defect. Congested bowel loop was pulled back and defect was approximated. An adult congenital omental defect is rare; however, it should be considered as one of the differential diagnoses in a relatively young patient with bowel obstruction without external hernia, previous abdominal surgery or trauma. PMID- 27656505 TI - Justifying No-Better Than Never. PMID- 27656504 TI - Aortopulmonary Window: A Rare Congenital Heart Defect. PMID- 27656507 TI - Diagnostic Performance of Ultrasonography for Detection of Abruption and Its Clinical Correlation and Maternal and Foetal Outcome. AB - INTRODUCTION: Placental abruption complicates about 1% of singleton pregnancies and is an important cause of perinatal mortality and morbidity. Though sensitivity and reliability of ultrasound are poor for detecting or excluding placental abruption, because of the advances in ultrasound resolution, imaging and interpretation, sensitivity of ultrasound is better than what was reported previously. AIM: To determine the diagnostic performance of Ultrasonography (USG) for the detection of placental abruption and whether sonographic results correlate with maternal and foetal management and outcome. MATERIALS AND METHODS: Thirty patients with clinical diagnosis of placental abruption were studied in the Obstetrics and Gynaecology Department of Krishna Institute of Medical Sciences, over a period of 6 months. These patients underwent ultrasonography for confirmation. Obstetric and neonatal outcome and sonographic results were compared and reviewed. Sonographic sensitivity and specificity and positive and negative predictive values were calculated. RESULTS: Incidence of abruption in present study was 1.56% (28 patients out of 1786 total deliveries). Sensitivity of ultrasonography in the diagnosis of abruption was 57% (CI 37.15%-75.57%) while its specificity was 100% (CI 15.81%-100%) with a positive predictive value of 100% (CI 79.42%-100%) and a 14% (CI 1.78% - 42.83%) negative predictive value. An 87.5% of patients(14 out of 16) with a positive USG finding of abruption had Intrauterine foetal Death (IUD)/still birth while 91.6% of patients (11 out of 12) with negative USG findings of abruption gave birth to babies who required NICU admission. CONCLUSION: Sonography is not sensitive for the detection of placental abruption but it is highly specific. Positive sonographic findings are associated with increased maternal morbidity, require more aggressive obstetric management and it is associated with worse perinatal outcome. In case of a negative USG finding, but a strong clinical suspicion of abruption if obstetric intervention is made in due time, foetal as well as maternal outcome are better. Foetal outcome also depends on gestational age. Preterm patients with positive USG and intrapartum findings of abruption have worse foetal outcome compared to full-term patients with abruption. PMID- 27656506 TI - Maternal Cardiac Diastolic Dysfunction by Doppler Echocardiography in Women with Preeclampsia. AB - INTRODUCTION: Preeclampsia may lead to heart failure in late pregnancy and early puerperium. Diastolic dysfunction may be the cause of heart failure in these patients. There is paucity of data on diastolic dysfunction in patients with preeclampsia. AIM: To assess cardiac diastolic dysfunction in women with preeclampsia by Doppler echocardiography and to correlate severity of dysfunction with severity of preeclampsia. MATERIALS AND METHODS: One hundred and fifty nulliparous women in age group of 20-35 years were recruited for the study. Among these, 120 women with preeclampsia were taken as cases and 30 normotensive women as controls. Doppler echocardiography was carried out between 28-36 weeks of gestation in both groups to assess and grade severity of diastolic dysfunction. RESULTS: Of 120 women with preeclampsia, 61 had mild preeclampsia and 59 had severe preeclampsia. Diastolic dysfunction was seen in 25(20.8%) cases. Among these, grade I diastolic dysfunction was seen in 40% and the rest 60% had grade II diastolic dysfunction. In the mild preeclampsia group, only 2(3.3%) patients had diastolic dysfunction. Both had grade I dysfunction. Of severe preeclampsia patients, 8(13.6%) had grade I and 15(25.4%) had grade II diastolic dysfunction (p=0.001). None of these progressed to heart failure or pulmonary oedema. Systolic function assessed by left ventricular ejection fraction was normal in all cases. All controls had normal systolic and diastolic functions. CONCLUSION: Cardiac diastolic dysfunction occurred in one-fifth of women with preeclampsia. Grade of diastolic dysfunction correlated with the severity of preeclampsia. PMID- 27656508 TI - Seroprevalence of Hepatitis B Infection among Pregnant Women in One of the Institute of Northern India. AB - INTRODUCTION: Hepatitis B Virus (HBV) occurs worldwide with more than 2 billion people being infected with HBV at some time in their lives. Transmission of HBV from carrier mothers to babies can occur during perinatal period and is important factor in determining the prevalence of infection in highly endemic areas. AIM: To assess the prevalence of hepatitis B infection, among otherwise healthy pregnant females. MATERIALS AND METHODS: This retrospective study analysed records of antenatal care registry from 1(st) April 2013 to 30(th) March 2014 at our institution. Details of a total of 3686 pregnant women subjected to screening of Hepatitis B surface antigen (HBsAg) using Enzyme Linked Immunosorbent Assay (ELISA) was recorded into a preset proforma. Data thus obtained has been analysed using SPSS version 13 and presented. RESULTS: Seroprevalence of HBsAg positive antenatal females was 1.11%. The mean age of HBsAg positive pregnant women was 24.98+/-4.16 years. Thirty one (75.61%) subjects hailed form a rural area. 4 (09.75%) and 3 (07.31%) subjects had HBV-HCV co-infection and HBV-HIV co infection respectively. Mean parity of women with HBV infection was 1.83+/-0.87. Most common age group with HBV infection was 25-30 years. CONCLUSION: Around 130 countries in the world are currently covered by routine hepatitis B immunization. High prevalence of seropositivity of HBsAg among antenatal female calls for routine vaccination against HBV infection. Universal free screening for HBV infection needs to be offered to all antenatal females on an opt-out basis to prevent the next generation from being grappled by chronic hepatitis, cirrhosis and hepatocellular carcinoma. PMID- 27656509 TI - Comparison of the Effect of Clomiphene- Estradiol Valerate vs Letrozole on Endometrial Thickness, Abortion and Pregnancy Rate in Infertile Women with Polycystic Ovarian Syndrome. AB - INTRODUCTION: Clomiphene citrate is the first-line therapy for ovulation induction in Polycystic Ovarian Syndrome (PCOS). This drug binds and blocks estrogen receptors and thought to have an anti estrogenic effect on endometrium volume, thus may have adverse effect on fertility. AIM: This study aimed to compare the effect of Clomiphene citrate plus Estradiol Valerate with Letrozole on endometrial thickness, abortion and pregnancy rate in infertile women with PCOS undergoing ovulation induction. MATERIALS AND METHODS: This was a randomized double blind clinical trial study on 100 women with PCOS, with an endometrial thickness less than 7mm in spite of follicles greater than 18mm after administration of Clomiphene citrate 100mg/d from 3(th) to 7(th) day of menstruation. They were randomly divided in two groups. Group A received 100mg Clomiphene citrate from day 3 to day 7 of menstruation and 4 mg Estradiol Valerate after the 8(th) day of menstruation until 14(th) day. Group B treated by 5mg Letrozole from day 3 to 7 of menstruation with placebo from 8(th) to 14(th) day of menstruation. In both groups endometrial thickness was measured by transvaginal sonography in the 14(th) day of menstruation. Data were analysed using SPSS Ver.18.0. RESULTS: The mean age was 30.34 years in group A and 29.62 years in group B (p=0.381). The number of infertility years in group A was 3.73 years and in group B was 3.85 years. There was no significant relationship statistically between the two groups in terms of mean age and infertility years (p=0.99). Endometrial thickness in group A was 7.26mm and in group B was 8.17 mm. Pregnancy rates in group A and group B was 32% and 16% respectively. There was significant relationship statistically between the two groups in terms of endometrial thickness and pregnancy rates (p=0.021 and p=0.05). There was no abortion in group A and 5 cases had abortion in group B, there was a significant relationship between the two groups statistically (p=0.028). CONCLUSION: Letrozole increased endometrial thickness and pregnancy rate in infertile women, therefore its administration is recommended. PMID- 27656510 TI - Frequency of Maternal Mortality in Urban and Rural Areas of Iranshahr County (Southeast of Iran) in 2009-2013: A Retrospective Study. AB - INTRODUCTION: Maternal mortality is one of the threatening factors of human life and the overall status index of women's health in any society. Death of a mother causes irreversible damage to a family and a society. This study aims at examining the causes of maternal mortality in urban and rural areas. AIM: The purpose of this study was to determine the frequney and causes of maternal mortality in urban and rural areas in southeast of Iran in 2009-2013. MATERIALS AND METHODS: This was a retrospective descriptive study and its research population includes the entire pregnant woman who died in Iranshahr County between April 2009 and March 2013. An eight-section questionnaire was used for collecting data. The first section was based on the hospital records of pregnant woman including mother's demographic data and the following sections were completed based on their health records. RESULTS: The frequency of maternal mortality during birth in the study period was 34 (of 4857). The study individuals were between 13 and 40-year-old with the mean age of 30+/-6.4. Maximum maternal mortality occurred in 2012. Haemorrhage was the most common cause of maternal death (38.2%). CONCLUSION: As haemorrhage was the most common cause of death of pregnant women in this study, it seems necessary to improve care for woman and reduce haemorrhage and its complications during pregnancy period. PMID- 27656511 TI - Efficacy of Intravenous Infusion of Acetaminophen for Intrapartum Analgesia. AB - INTRODUCTION: The intensity of pain experienced by women in labour, has been found to affect the progress of labour, foetal well-being and maternal psychology. Adverse effects associated with commonly used opioids for providing intrapartum analgesia have created a need for an alternative non-opioid drug. AIM: To evaluate the efficacy of an intravenous infusion of 1000 mg of acetaminophen as an intrapartum analgesic. MATERIALS AND METHODS: The present prospective single-centre, single blind, placebo-controlled randomized interventional study was conducted in Department of Obstetrics and Gynaecology in Vardhaman Mahavir Medical College & Safdarjung Hospital over a period of six months from September 2014 to March 2015. After receiving the ethical clearance and written informed consent. The first 200 consecutive parturients fulfilling the inclusion criteria were recruited into the study. Women were then randomised to receive either intravenous 1000 mg (100ml) of acetaminophen (Group A, n=100) or 100 ml normal saline (Group B, n=100). Primary outcome assessed was effectiveness of acetaminophen to provide an adequate amount of analgesia, as measured by a change in Visual Analogue Scale (VAS) pain intensity score at various times after drug administration. Secondary outcomes measured were duration of labour, need for additional rescue analgesia and presence of adverse maternal or foetal effect. RESULTS: There was pain reduction at 1 and 2 hours in both groups (p<0.001). However, it was more significant in the acetaminophen group, especially at 1 hour. Duration of labour was shortened in both the groups, without any maternal and foetal adverse effects. CONCLUSION: Intravenous acetaminophen is an efficacious non-opioid drug for relieving labour pain without any significant maternal and foetal adverse effects. PMID- 27656514 TI - An Incidental Finding of Bilateral Dysgerminoma During Cesarean Section: Dilemmas in Management. AB - Dysgerminoma is an uncommon malignant tumour arising from germ cells of ovary. It occurs mostly in the reproductive age group. Its association with pregnancy is rare. Its management remains a challenge especially in an unsuspected case. We present a case of a woman, aged 28-year-old gravida2 para1 who reported to us at 36 weeks' pregnancy with severe preeclampsia and previous caesarean section. On ultrasound she was reported as having subserosal fibroids with single live fetus of 35 weeks and 3 days gestation. She delivered a live baby by caesarean section done for failed induction. Intraoperatively bilateral ovarian masses were found and removed which were later confirmed to be dysgerminoma on histopathological examination. As she was not diagnosed dysgerminoma pre-operatively, complete work up i.e., tumour markers and MRI was not done, leading to dilemmas in management. Though standard protocols for management of dysgerminoma with pregnancy exist, yet management of these incidentally diagnosed dysgerminomas remains a dilemma. PMID- 27656512 TI - A Clinical Experience of Ectopic Pregnancies with Initial Free Intraperitoneal Fluid. AB - INTRODUCTION: Extra-uterine pregnancy or Ectopic Pregnancy (EP) is a major health problem for pregnant women, presenting as a potentially life-threatening emergency in the first trimester. There are three major options for the treatment of EP: expectant management, surgical treatment and medical management. The presence of free intraperitoneal fluid in EP-diagnosed patients is crucial for treatment planning and evaluation. AIM: To compare the outcomes of both the expectant man-agement and medical treatment with methotrexate (MTX) in ectopic pregnancies with free intraperitoneal fluid. MATERIALS AND METHODS: This retrospective cohort study inclu-ded a total of 91 ectopic pregnancies with or without rupture in which the women had initial free intraperitoneal fluid and were haemodynamically stable. Serial beta-HCG measurements were used to assess the outcome of expectant management and medical treatment with MTX. For the statistical analysis, the SPSS statistical software package, version 22.0 (Chicago, IL, USA), was used. For the quantitative variables that were not distributed normally, the Kruskal-Wallis test and the Mann-Whitney U test were performed for the evaluation of differences between the groups. RESULTS: It was observed that the success rate with expectant management was 81% (initial beta HCG concentration 626+/-443 mIU/mL). With a single dose of MTX, it was 76% (initial beta HCG concentration 2124+/-1647 mIU/mL) and with a total single or double dose of MTX, it was 88% (initial beta HCG concentration 2252+/-78 mIU/mL) from among EP with or without rupture in women with initial free intraperitoneal fluid during diagnosis. There was no significant difference between the groups with regard to ultrasonography findings. CONCLUSION: Expectant management or medical treatment with methotrexate should be the first line treatment for ectopic pregnancies with initial free intraperitoneal fluid, albeit with rupture, in patients who are haemodynamically stable, along with beta-HCG follow-up. PMID- 27656513 TI - Urethral Coitus in a Case of Vaginal Agenesis - Is Only Vaginoplasty Enough to Treat the Urinary Problems? AB - Urethral coitus is an extremely rare condition. Megalourethra and urinary incontinence due to urethral coitus in vaginal agenesis are unusual manifestations because these patients usually present with primary amenorrhea before becoming sexually active and receive treatment. A 24-year-old woman came to our clinic because of primary amenorrhea, sexual dysfunction, dyspareunia, megalourethra and urinary incontinence five months after her marriage due to urethral coitus. Based on these clinical and radiological findings a diagnosis of Mayer-Rokitansky-Kuster-Hauser Syndrome was made and patient underwent modified McIndoe Vaginoplasty. The elasticity of female urethra permits repeated coitus, together with the physical damage can probably lead to incontinence. In this case, after eliminating the underlying cause of disease with vaginoplasty, no other treatment was required. The integrity of sphincteric function and structural support of urethra might be regained without subjecting the patient to aggressive reconstructive surgical procedures. PMID- 27656515 TI - Outcome Analysis of Locking Plate Fixation in Proximal Humerus Fracture. AB - INTRODUCTION: Proximal humerus fractures account for approximately 5% of all fractures. Stable minimally displaced fractures can be treated nonoperatively but the management of displaced fractures remain controversial with various modalities of treatment available. Locking plates provide stable fixation and enable early postoperative mobilization specially in osteoporotic proximal humerus fracture. AIM: To evaluate the functional outcome of locking plate fixation and to compare the results of two approaches used for fixation. MATERIALS AND METHODS: This prospective study was conducted at a tertiary level hospital between September 2011 to December 2013. PHILOS plates were used for internal fixation of displaced proximal humerus fractures Neer's type 2 part, 3 part and 4 part fractures on 26 patients (M/F ratio 1.36:1; mean age 46 years). According to Neer classification, 5,12 and 9 patients had displaced 2, 3 and 4 part fractures respectively. Deltopectoral and deltoid splitting approaches were used for fixation on 13 patients each. Functional outcome was assessed using Constant-Murley shoulder score. Graphpad software version 6.0 was used with Chi square test and Fisher-exact test are used to compare data. The p-value< 0.05 is considered significant. RESULTS: Of the 26 patients, all fractures united radiologically and clinically and average constant score at final follow-up was 72.5. At the final follow-up 8 patients had good score, 10 patients had moderate score, 6 patients had excellent outcome and 2 patients had poor outcome according to Constant score. Mean time to union was 12.3 weeks (9 -15 weeks). Four complications (15.4%) were encountered, 2 cases of varus malunion, 1 case of wound infection which required wound debridement and 1 case of screw cut-out in which screw removal was done. Mean constant score in delto splitting approach was 70.9 and 74 in deltopectoral group (p-value= 0.54). No significant difference existed in constant score in 2 approaches. No significant difference existed between groups in terms of complications (P > .05) and all fractures were united. CONCLUSION: Our study demonstrates that locking plate fixation gives good functional outcomes in treatment of proximal humerus fractures. There was no significant difference in the two approaches used for exposure. Our results are comparable to various studies conducted by other authors which states that locking plates provide better functional and radiological outcomes as compared to other fixation methods like Tension band wiring, percutaneous K-wire fixation, non-locking plates, intramedullary nails. PMID- 27656516 TI - Delayed Open Reduction and K-Wire Fixation of Widely Displaced Supracondylar Fractures of Humerus in Children using Medial Approach. AB - INTRODUCTION: Supracondylar fractures of humerus in children are usually treated with percutaneous pinning on emergency basis. When the operating time is delayed, percutaneous pinning is difficult due to massive swelling. Late presentation is common in developing countries. AIM: To assess the outcome of open reduction and internal fixation with K-wire of widely displaced supracondylar fracture when operated later than 2 days after the injury. MATERIALS AND METHODS: A total of 52 children (aged 3-12 years) with widely displaced supracondylar fracture of humerus (Gartland type-III) who presented later than 2 days after injury were treated with open reduction through medial approach and fixation with cross K wires. RESULTs were assessed with Flynn's criteria. RESULT: A total of 40 patients completed follow-up. Mean age of all (n=52) patients was 4.8 years (range 3-12 years). Mean delay of presentation was 7.5 days (range 2-14 days). Hundred percent patients had satisfactory results according to Flynn's criteria. Two patients had pin infections. CONCLUSION: Open reduction through medial approach and fixation with two cross K-wires is a reliable method of treatment for supracondylar fractures of humerus in children when the operation is delayed. PMID- 27656517 TI - Role of Percutaneous Image Guided Biopsy in Spinal Lesions: Adequacy and Correlation with MRI Findings. AB - INTRODUCTION: Although, MRI has increased our understanding of spinal pathologies, accurate diagnosis of spinal lesions need biopsy, so that early treatment can be initiated. AIM: To evaluate the accuracy of biopsy, safety and yield of percutaneously done image guided spinal biopsy using a large bore needle and correlate between MRI findings and biopsy as well as the importance of various MRI findings in establishing the diagnosis. MATERIALS AND METHODS: All spinal lesions after clinical and MRI evaluation were subjected to Jamshidi Needle biopsy using 11 gauge needles. Biopsy material was sent for culture/sensitivity, AFB smear and histopathological examination. The outcome assessment included percentage of patients in whom diagnosis was changed after biopsy, yield in biopsy and complications of biopsy. MRI findings, biopsy findings and final diagnosis were correlated to know the sensitivity and specificity of MRI and biopsy diagnosis. Logistic regression analysis was used to study the importance of each of MRI findings in making a diagnosis. RESULTS: Forty five patients with spinal lesions underwent biopsy using an 11 gauge Jamshidi needle. Initial biopsy was inconclusive in 4 patients giving a positive yield in about 91.2% of cases and a repeat biopsy ensured conclusive report in all cases. Following biopsy there was a change in diagnosis in 8% cases. MRI showed sensitivity of 85.71% and specificity of 93.54% for the diagnosis of malignancy and sensitivity of 85.71% and specificity of 86.48% for the diagnosis of tuberculosis. In contrast, initial biopsy had sensitivity of 92.85% and specificity of 100% for the diagnosis of malignancy and sensitivity of 71.42% and specificity of 100 % for the diagnosis of infection. Logistic regression analysis showed good correlation between malignancy and posterior bugle in the vertebral body in the absence of a fracture (p = 0.007), involvement of pedicles and posterior elements (p = 0.001) and soft tissue extension (p = 0.002); there was good correlation between infection and epidural abscess (p<0.001) as well as paradiscal involvement (p<0.001). CONCLUSION: Image guided biopsy done with good technique helps in accuracy of diagnosis thus ensuring the correct treatment at the earliest and has minimal complications. This study also shows that presence of epidural abscess and paradiscal involvement in MRI are highly suggestive of infection, while pedicle involvement and posterior bulge of vertebral body before the onset of pathological fracture are suggestive of malignancy, but all spinal lesions should be biopsied to confirm the diagnosis. PMID- 27656518 TI - Type IIA Monteggia Fracture Dislocation with Ipsilateral Distal Radius Fracture in Adult - A Rare Association. AB - Monteggia fracture constitutes about 5-10% of the forearm fractures. Monteggia fracture by definition is proximal ulnar fracture with disruption of proximal radioulnar joint. Bado classified Monteggia fracture dislocation into four types and Jupiter subclassified type II Bado's fractures into four types. The associated injury in the form of distal radial fractures and distal humerus fractures are rare though many cases of distal radial physeal injuries have been reported in paediatric population. Hereby we report a rare association of type IIA Monteggia fracture dislocation with ipsilateral distal radius fracture in an adult patient. This case report also highlights on proper examination and full length radiographs of forearm to avoid missing injury at wrist in cases of elbow injuries. Management of such complex injuries included open reduction and internal fixation of olecronon fracture, distal radius fracture and radial head resection. Functional outcome at six months was good at wrist whereas at elbow, stiffness was a major concern with elbow range of movement from 40 degrees -110 degrees . PMID- 27656519 TI - Tissue Doppler Imaging and Focal, Late-Onset Anthracycline-Induced Cardiovascular Disease in Long Term Survivors of Childhood Cancer: A Research Article. AB - INTRODUCTION: In anthracycline-induced cardiomyopathy, the onset of diastolic dysfunction occurs before systolic dysfunction. Although, conventional echocardiogram is the standard method to assess cardiac function post anthracycline therapy, Tissue Doppler Imaging (TDI) may detect early onset cardiac diastolic dysfunction among anthracycline-recipient survivors of childhood cancers. There are limited data on the use of TDI in assessing anthracycline-associated cardiotoxicity in children. AIM: To evaluate the role of Tissue Doppler Imaging (TDI) in assessing late-onset cardiotoxicity in survivors of paediatric cancers. MATERIALS AND METHODS: This was a single site, observational, blinded study of 11 long-term survivors of childhood cancer who had been treated with anthracyclines and 22 age-matched controls. The study group and the control group underwent conventional echo and TDI; operators were blind to study group. Conventional echo measurements were obtained. TDI was used to assess systolic and diastolic parameters at the mid-interventricular septum and lateral and medial annuli of the mitral valve; these parameters included: systolic wave (S'), early diastolic wave (E'), late diastolic wave (A'), Isovolemic Contraction Time (ICT), Isovolemic Relaxation Time (IRT) and Ejection Time (ET). Myocardial Performance Index (MPI) was also calculated. RESULTS: Conventional echo measurements were similar in both groups. Using TDI, cases had a lower mean E' velocity (9.7 +/- 1.7 cm/s vs. 11.4 +/- 1.3 cm/s, p=0.004) and a lower E'/A' (1.8 +/- 0.5 vs. 2.2 +/- 0.4, p=0.022) at the mid-interventricular septum than controls. The mean E' septum velocity in chemotherapy-recipients who also received chest radiotherapy was 8.5+/-0.5 cm/s in comparison to 10.2+/-1.7 cm/s in those that did not receive chest radiotherapy but this not achieve statistical significance. We did not find any additional associations between TDI parameters and patients' gender, age of diagnosis, length of follow-up and dose of anthracycline. CONCLUSION: In long-term survivors of childhood cancer who received anthracyclines, diastolic dysfunction can be detected earlier by using TDI before overt systolic dysfunction. Further large-scale multicenter studies are needed. PMID- 27656520 TI - Demographic, Clinical and Hematological Profile of Children with Bronchiolitis: A Comparative Study between Respiratory Synctial Virus [RSV] and [Non RSV] Groups. AB - INTRODUCTION: Acute bronchiolitis is one of major disease affecting the lower airways in infants and children with Respiratory Syncitial Virus (RSV) being most common causative organism accounting for 50%-80% of bronchiolitis cases. AIM: To analyse the demographic characteristics, clinical features and haematological profile of children with Bronchiolitis. To compare the findings of demographic characteristics, clinical features and haematological profile between RSV and Non -RSV bronchiolitis. MATERIALS AND METHODS: This is a prospective study, conducted in a teritiary care center for 1 year period from Jan 2015 to Dec 2015. The demographic characteristics, clinical features and haematological profile of children aged between 1 month to 3 years who fulfilled the inclusion criteria were noted in predesigned proforma, nasopharyngeal swab was sent for RSV analysis and then the findings of the parameters were compared between the two groups of RSV bronchiolitis and Non RSV bronchiolitis. RESULTS: Among 80 cases with 40 in each group, children below the age of 1year were affected more in RSV group, with male preponderance. Among the clinical features except that 89.7% of RSV cases had wheeze that was statistically significant with no difference in other features. Investigations showed no much difference in both the groups. Percentage of Non RSV subjects who received nebulisation with bronchodilators, steroid and antibiotic therapy were higher than RSV subjects. The hospital stay was significantly higher in RSV cases and none of the study participants met with mortality. CONCLUSION: Children with RSV bronchiolitis had prolonged hospital stay compared to Non RSV group. Need for nebulisation with bronchodilators, steroids and antibiotic therapy was more in Non RSV group. PMID- 27656521 TI - A Case with Complete Pancreatic Aplasia Suggestive of Johanson-Blizzard Syndrome. AB - Johanson-Blizzard Syndrome (JBS) is a very rare autosomal recessive multisystem disorder. We report the case of a two-month-old male with pancreatic insufficiency and severe phenotypic features. His diagnosis of JBS was established using clinical symptoms and abdominal computed tomography scan that showed pancreas aplasia. According to the best of our knowledge, no case with this syndrome has presented with complete pancreatic aplasia in the literature. PMID- 27656522 TI - Is Chromosomal Study Necessary for Girls with Inguinal Hernia? PMID- 27656523 TI - Role of Gray Scale, Color Doppler and Spectral Doppler in Differentiation Between Malignant and Benign Thyroid Nodules. AB - INTRODUCTION: High resolution ultrasound is the most sensitive imaging test available for the examination of the thyroid gland and due to increase in use of ultrasound more incidental thyroid nodules are diagnosed. In this study we try to establish the specific grayscale, color and spectral Doppler characteristics of malignant and benign thyroid nodules. AIM: To determine the specific gray scale characteristics, angioarchitecture and cut-off values of Doppler indices of malignant and benign thyroid nodules. To assess the efficacy of grayscale, Doppler and combined conventional and Doppler using defined criteria in differentiating malignant from benign nodules. MATERIALS AND METHODS: We prospectively examined 194 thyroid nodules which were confirmed on FNAC. Each nodule was described according to size, number, contents, echogenicity, margins, halo, shape, calcification, local infiltration and lymphnode enlargement. Vascularity, RI and PI values of each nodule were assessed on Doppler. Each nodule was characterized as benign, indeterminate or malignant based on grayscale and Doppler characteristics. Cut-off RI and PI values for malignant thyroid nodules were obtained by ROC. RESULTS: Out of 194 nodules, 151 nodules were benign and 43 nodules were malignant. Significant relationship was observed between malignancy and hypoechogenicity, irregular margins, taller than wide, thick incomplete halo, micro calcifications, lymphnode enlargement and local infiltration. Intranodular vascularity was a significant criterion to suggest malignancy in thyroid nodules on color Doppler. Malignant nodules had a mean RI of 0.73 and mean PI of 1.3 which were significantly higher than the benign nodules. Accuracy of detecting malignant thyroid nodules by combining gray scale and Doppler is higher than either of them alone. CONCLUSION: Using specific morphological pattern recognition features like microcalcifications, hypoechogenicity, taller than wide, irregular thick halo, lymphadenopathy and local extra thyroidal invasion has helped in differentiating malignant from benign features. Intranodular vascularity and high RI indices were the specific Doppler signs for malignant thyroid nodules. Since, Gray scale and Doppler have their own strengths and weaknesses, they were complementary rather than competitive modalities in diagnosing benign from malignant thyroid nodules. PMID- 27656524 TI - Assessment of Portal Venous and Hepatic Artery Haemodynamic Variation in Non Alcoholic Fatty Liver Disease (NAFLD) Patients. AB - INTRODUCTION: Non-Alcoholic Fatty Liver Disease (NAFLD) has various spectrums of liver diseases like isolated fatty liver, steatohepatitis and cirrhosis usually progressing in a linear fashion. In this process they are known to cause certain haemodynamic changes in the portal flow and hepatic artery flow. AIM: The aim of the study was to study these haemodynamic changes in patients with NAFLD and to correlate it with the disease severity. MATERIALS AND METHODS: Ninety patients diagnosed to have NAFLD based on ultrasound abdomen (30 each in grade1, grade2 and grade3 NAFLD) and 30 controls (Normal liver on ultrasound abdomen) were subjected to portal vein and hepatic artery Doppler study. Peak maximum velocity (Vmax), Peak minimum velocity (Vmin), Mean flow velocity (MFV), and Vein pulsality index (VPI) of the portal vein and hepatic artery resistivity index (HARI) of the hepatic artery were the doppler parameters which were assessed. Liver span was also assessed both for the fatty liver and controls. RESULTS: The mean Vmax, Vmin, MFV and VPI of the portal vein in patients with NAFLD was 12.23+/-1.74cm/sec, 9.31+/-1.45cm/sec, 10.76+/-1.48cm/sec, and 0.24+/-0.04 as compared to 14.05+/-2.43cm/sec, 10.01+/-2.27cm/sec, 12.23+/-2.47cm/sec, 0.3+/ 0.08 in controls respectively. All these differences were statistically significant except for Vmin. The Mean HARI in patients with fatty liver was 0.65+/-0.06 when compared to controls of 0.75+/-0.06 (p=0.001). HARI (r-value of 0.517) had a better negative correlation followed by VPI (r-value of -0.44) and Vmax (r-value of -0.293) with the severity of NAFLD. MFV had a very weak negative correlation (r-value of -0.182) with the severity of NAFLD. CONCLUSION: The Vmax, MFV, VPI and HARI were significantly less when compared to controls suggesting a reduced portal flow and an increased hepatic arterial flow in patients with NAFLD. Among the parameters, HARI correlated better with the severity of NAFLD followed by VPI. PMID- 27656525 TI - Digital Paper Prints as Replacement for LASER Films: A Study of Intra-Observer Agreement for Wrist Radiographic Findings in Rickets. AB - INTRODUCTION: Replacement of conventional LASER films with digital paper prints as supplement to radiology reports may serve as an economical and environment friendly method. However, it is essential that such a change does not compromise patient's intended diagnostic outcome. AIM: The aim of this study was to assess the reliability and acceptability of digital paper prints for the radiographic images by the treating physicians and radiologists. MATERIALS AND METHODS: This observational analytical study was done at a tertiary care hospital of New Delhi, India. A total of 58 consecutively ordered wrist radiographs of paediatric patients (6 months to 12 years of age) for ruling out rickets were retrieved from the PACS (Picture Archiving and Communication System). These 58 radiographs, out of which 21 (36.2%) had radiological evidence of rickets over PACS were printed on two different media i.e., LASER films and glossy photographic paper. An objective scoring for the severity of rickets was done on both LASER films and paper prints by six observers independently. Overall comfort level with paper prints was rated on a 1-5 point Likert scale. Data was analysed using STATA 14.0 (Stata Corp, College Station, TX). RESULTS: Intra-observer percentage agreement and value of Cohen's kappa for PACS vs. LASER films and PACS vs. paper prints was equal i.e., 98.3% and 0.97, respectively. Intra-observer agreement between LASER films and paper prints for all six observers was excellent, ranging from 0.92 to 1.00; percentage agreement ranging from 94.8% to 100%. Fracture of ulna/radius present in 4 sets of the X-rays was well demonstrated in both LASER films and paper prints. Comfort level with paper prints was rated as 5 out of 5 by all due to no requirement of any special illuminated view box and dark room. CONCLUSION: This study concludes that the use of paper prints may serve as a reliable alternative to LASER films to communicate the report of wrist radiographs for the treating physicians without any compromise over diagnostic information in cases of rickets. PMID- 27656527 TI - Evaluation of Apparent Diffusion Coefficient Values in Spinal Tuberculosis by MRI. AB - INTRODUCTION: Spinal tuberculosis presents a radiological challenge in many cases when it presents with atypical pattern of involvement and has to be distinguished from various differentials, which include metastases. In such cases Diffusion Weighted Imaging (DWI) with Apparent Diffusion Co-efficient (ADC) value may play a role in reaching towards a conclusion, thereby preventing unnecessary biopsy in such patients. AIM: Measurement of mean ADC values in tubercular vertebrae and associated collection. MATERIALS AND METHODS: The study was comprised of 55 patients and was conducted on 3.0 TESLA Siemens machine Magnetom Verio. Patients either known to have tuberculosis or those with classic tuberculous findings were included in the study. All these patients were followed up for post-treatment confirmation and ADC value. All the patients underwent routine MRI along with DW MRI sequence, ADC values and FNAC/ Biopsy if required. The ADC values were calculated from the involved vertebral bodies and surrounding soft tissue and also from normal vertebrae preferably from one above and below the affected vertebrae to establish ADC of normal vertebrae, which was helpful in treatment response in patients with antitubercular therapy. At least six ADC value was taken from affected vertebrae and soft tissue. RESULTS: The mean ADC value of tubercular vertebrae was found out to be 1.47 +/- 0.25 x 10(-3) mm(2)/sec, of adjacent soft tissue collection (abscess) was 1.94 +/- 0.30 x 10(-3) mm(2)/sec and normal vertebrae was 0.48 +/- 0.16 x 10(-3) mm(2)/sec. ADC value of post treated vertebrae decreased and complete resolution showed ADC near normal vertebrae. CONCLUSION: Normal range of the ADC values in spinal tuberculosis and associated paravertebral collection may be helpful in the differentiation of spinal tuberculosis from lesions with spinal involvement which are not proven to be tuberculosis and who did not have the classical appearance of either tuberculosis or metastasis. But there exists a zone of overlap of ADC values in metastatic and tubercular vertebrae, which can lead to false negative results. Therefore, in overlap cases there should be correlation with clinical history, other related investigations or biopsy. PMID- 27656526 TI - Comparative Evaluation of Ultrasonography and Cross-sectional Imaging in Determining Gall Bladder Perforation in Accordance to Niemeier's Classification. AB - INTRODUCTION: Gall Bladder (GB) perforation, a rare but dreaded complication of acute cholecystitis and is associated with high mortality rate. Early detection of acute cases of GB perforation reduces the risk of biliary peritonitis and hence the associated mortality and morbidity. AIM: The purpose of the study was to make a comparative evaluation of the role of Cross-sectional imaging in GB perforation with base line investigation like sonography. Finally both modalities were compared in determining the type of perforation according to Niemeier's classification. MATERIALS AND METHODS: We retrospectively evaluated the Ultrasonography (USG), Computed Tomography (CT) and Magnetic Resonance Imagings (MRI) findings in patients of GB perforation with surgical correlation. RESULTS: We evaluated 17 patients of GB perforations over a time period of one year. USG was done in all patients. As cross-sectional modality only CT scan was done in 14 patients and MRI scan was done in four patients. Both CT and MRI scans were done in one patient. CONCLUSION: Cross-sectional imaging must not be delayed in suspected cases of GB perforations because it helps in establishing a quicker diagnosis, detecting complications and also helps in decision making related to management thereby reducing the morbidity and mortality associated with this condition. PMID- 27656528 TI - Effect of Dipyridamole Injected for Myocardial Perfusion Imaging on Blood Glucose Concentration; A Preliminary Study. AB - INTRODUCTION: Dipyridamole inhibits adenosine reuptake and increases cyclic Adenosine Monophosphate (cAMP) levels in platelets, erythrocytes and endothelial cells, all of which influence blood glucose. Acute hyperglycaemia reduces endothelium-dependent vasodilation and suppresses coronary microcirculation; which, in theory, can alter the outcome of a radionuclide scan. AIM: The present study was conducted with the aim to investigate the changes in blood glucose level of patients receiving dipyridamole for cardiac scan. MATERIALS AND METHODS: A total of 293 patients (85 men and 208 women, age: 60.59+/-10.43 years) were included in the study. Fasting Blood Glucose (FBG) was measured before and 8 min after dipyridamole (0.568 mg/kg) injection during myocardial perfusion imaging. The data in different groups were analysed by paired t-test. RESULTS: There was not a significant difference between first (106.89 +/- 19.21mg/dL) and second (107.98 +/- 17.57 mg/dL) FBG measurements (p= 0.293). However, when the patients were grouped based on the quartiles of first measurement, there was an increase in FBG following dipyridamole injection in the first quartile (mean difference: 7.15+/-21.27 mg/dL, p<0.01); in contrast, FBG levels showed a significant decrease after dipyridamole administration in the 4(th) quartile (mean difference: -9.53+/-18.20 mg/dL, p<0.001). The differences in 2(nd) and 3(rd) quartiles were negligible. The patients were divided into normal, ischemic and fixed lesions based on the outcome of scans, then the possible correlation of dipyridamole-induced FBG alteration and scan results were investigated. There were no significant difference between the FBG values before and after dipyridamole injection and the final outcome of scan. CONCLUSION: The effects of dipyridamole on blood glucose highly depend on the initial blood glucose level. PMID- 27656529 TI - Osteochondroma of Bilateral Mandibular Condyle with Review of Literature. AB - Osteochondroma (OC) is a common slow growing tumour of bone. This lesion is frequently seen in the axial skeleton and is relatively uncommon in oral and maxillofacial region. In facial bones, it usually affects the mandibular condyle followed by coronoid process. Very few cases of condylar osteocondroma have been reported in the literature. The aim of this article was to present an atypical case of osteochondroma of bilateral mandibular condyle in an asymptomatic patient and facilitate making an exact diagnosis of it. To the best of our knowledge this is the 2(nd) case of this type reported in literature. PMID- 27656530 TI - Letter Regarding Article, 'Unusual Presentation of Dengue Fever Cerebral Venous Thrombosis'. PMID- 27656531 TI - A Comparative Study of Dexmedetomidine and Midazolam in Reducing Delirium Caused by Ketamine. AB - INTRODUCTION: Ketamine is a well known agent for sedation for short surgical procedures due to its very good analgesic action. But it has cardio stimulatory response and recovery from anaesthesia after Ketamine use is complicated by delirium and hallucination. In studies it is proved that these side effects can be reduced by premedication with benzodiazepines. The alpha2 adrenoceptor agonists are becoming popular for their properties like haemodynamic stability and reducing anaesthetic requirement. AIM: This study was planned to see the effects of Dexmedetomidine on emergent reaction of Ketamine, when used as premedication agent with Ketamine for conducting short surgeries in adult patients. MATERIALS AND METHODS: Study was conducted in 90 ASA class I and II male and female patients of age between 18-40 undergoing short procedures like laparoscopic ligation, skin grafting, dilatation and curettage, endoscopic procedures, excision of small swelling, etc. Patients were randomly divided into three groups of 30 each as follows: Group K: after premedication with inj. glycopyrrolate 0.01mg/kg, inj. Ketamine 2mg/kg, Group M: after premedication with inj. glycopyrrolate 0.01mg/kg and inj midazolam 0.05mg/kg, inj. Ketamine 2mg/kg, Group D: after premedication with inj glycopyrrolate 0.01 mg/kg and inj. Dexmedetomidine 0.5MUg/kg, Ketamine 2mg/kg was given. Observations were made for cardiovascular response to invasive procedure, post anaesthetic anxiety and delirium with help of Memorial Delirium Assessment scale (MDAS). RESULTS: Midazolam reduced delirium to a greater level, but in comparison to control group and midazolam group, dexmedetomidine reduced delirium to a much greater level (p value<0.001). Postoperative pain was less in Dexmedetomidine group (p-value< 0.001). CONCLUSION: Dexmedetomidine reduced delirium caused by Ketamine when used as a premedication agent. It produced more haemodynamic stable patients. Postoperative analgesia was also better. PMID- 27656532 TI - Comparison between IV Paracetamol and Tramadol for Postoperative Analgesia in Patients Undergoing Laparoscopic Cholecystectomy. AB - INTRODUCTION: Efforts to use safer drug with minimal side effects for postoperative analgesia are growing day by day for surgeries of shorter duration or which may require day care only, search for ideal agent has been a never ending process. AIM: The aim of the present study was to compare the efficacy of intravenous Paracetamol and Tramadol for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. MATERIALS AND METHODS: This study was done at Department of Anaesthesiology, Era's Medical College, Lucknow, India. Sixty ASA-I or II patients between 18-55 years of age, scheduled for laparoscopic cholecystectomy were randomly allocated to two groups of 30 each. Group A received IV infusion of paracetamol 1g in 100 ml solution, while Group B received IV infusion of Tramadol 100 mg in 100 ml NS at 0 (first complain of pain postoperatively), 6, 12 and 18 hours respectively. Pain intensity was measured by a 10 point Visual Analogue Scale (0->no pain and 10->worst imaginable pain) VAS at T(0)->just before analgesic administration, at 0.5, 1.5, 3, 6, 12, 18 and 24 hours thereafter, in addition to HR, SBP, DBP. STATISTICAL ANALYSIS: Chi-square test, Student t-test and p-values <0.05 was considered significant. RESULTS: During postoperative follow-up intervals, paracetamol showed significantly lower VAS scores as compared to tramadol at 1.5 hour, 3 hour, 6 hour, 12 hour and 24 hour follow up intervals. One patient in tramadol group had nausea postoperatively (p>0.05). No adverse effect attributable to paracetamol was noticed. CONCLUSION: Intravenous Paracetamol can be advocated as an effective and safe analgesic agent for postoperative pain relief. PMID- 27656533 TI - Comparison of 0.25% Ropivacaine for Intraperitoneal Instillation v/s Rectus Sheath Block for Postoperative Pain Relief Following Laparoscopic Cholecystectomy: A Prospective Study. AB - INTRODUCTION: As Laparoscopic Cholecystectomy (LC) is not a totally pain free procedure, with the pain being most intense on the day of surgery and on the following day. Various techniques are available for postoperative pain relief like intraperitoneal instillation of local anaesthetics and rectus sheath block (RSB)which may provide effective pain relief. AIM: To compare the efficacy of preemptive administration (initiated before the surgical procedure) of intraperitoneal instillation and rectus sheath block using ropivacaine for postoperative analgesia after laparoscopic cholecystectomy. MATERIALS AND METHODS: A total of 75 selected patients were randomly assigned to three equal groups as Group R, who received bilateral RSB with 0.25 % ropivacaine 15 ml on either side; Group I, who received intraperitoneal instillation of 0.25% ropivacaine 50 ml and Group C (Control group), who received only rescue analgesic on pain. These were compared regarding postoperative analgesia in terms of Visual Analog Scale (0-10 cm), Prince Henry Hospital Pain Score (0-3), time to first dose of rescue analgesic (tramadol), total rescue analgesic consumption in 48 hours, patient satisfaction scores (1-7) and adverse effects. RESULTS: The time to first rescue analgesic was significantly longer in Group R (16.16+/-4.73h) and Group I (7.84+/-1.34h) as compared to Group C (1.72+/-0.67h), p<0.001. Mean tramadol consumption in 48h for each patient was significantly less in Group R (148+/-54.92mg) and Group I (202+/-33.78mg) as compared to Group C (298+/ 22.73mg) p<0.001. Postoperative pain scores were also significantly less in Group R and Group I as compared to Group C during first 6 hours, p<0.05. The difference in above parameters was also significant between Group R and Group I, p<0.05. Thus order of postoperative analgesia effect was: Group R > Group I > Group C. Rescue analgesic requirement showed a 32.21% reduction in Group I and 50.33% reduction in Group R as compared to Group C. Patient Satisfaction Scores (PSS) showed a significant difference among groups with acceptable PSS scores as: Group R (92%) v/s Group I (40%) v/s Group C (20%) p<0.001. CONCLUSION: Pre-emptive administration of rectus sheath block or intraperitoneal instillation of 0.25% ropivacaine was found effective in providing better postoperative analgesia as compared to control group after laparoscopic cholecystectomy. Among these two techniques, rectus sheath block was found to be superior over intraperitoneal instillation. PMID- 27656534 TI - Congenital Lobar Emphysema: An Approach of Anesthetic Management. AB - Congenital Lobar Emphysema (CLE) is a medical condition which is quiet rarely seen especially in neonates. The disease is characterized by over inflation of lungs which is produced due to inhibition of escape of inspired air from lungs. This condition usually occurs in infants due to partial obstruction of the bronchus and can be reversed with timely and planned anaesthetic management. Here in, we are presenting a case of an infant who was merely four months of age. CLE was affecting his left upper lobe since birth which was being treated as lobar pneumonia outside at some peripheral health center. The case presented to hospital with the symptoms acute respiratory distress and was taken up for urgent surgical management. Left upper lobectomy was performed which relived his symptoms. Case was discharged from hospital after 10 days of uneventful hospital stay. The case was challenging, as it involved careful and planned anaesthetic management of lung separation as well as prevention of hyperventilation of the un involved lung. PMID- 27656535 TI - Comparative Study of Delirium in Emergency and Consultation Liaison- A Tertiary Care Hospital Based Study in Northern India. AB - INTRODUCTION: Delirium is an acute and often fluctuating disturbance in level of consciousness and thought process (cognition) that develops over a short period of time and is a significant change from previous level of functioning. Its prevalence increases with age, complexity of medical co- morbidities and number of medications prescribed. AIM: To compare the cause and severity of delirium in patients in emergency and consultation liaison psychiatry group. MATERIALS AND METHODS: A cross-sectional, tertiary care hospital based study was conducted on the patients who presented with delirium from emergency department (50) and consultation-liaison psychiatry groups (50), over a period of one year. The diagnosis was made on the basis of DSM- 5 criteria. The Delirium Rating Scale (DRS-R-98) was applied to know the severity of delirium, cognitive and non cognitive symptoms of delirium in patients. The results were subjected to appropriate statistical analysis. RESULTS: In emergency group, 42% patients had metabolic abnormalities, while in consultation-liaison, 38% patients had hyponatremia and hypokalemia and the difference was found to be statistically non significant (p>0.05). In emergency group, 21(42%) patients were diagnosed as delirium due to other medical condition, followed by 13 (26%) and 8(16%) patients, who were diagnosed as delirium due to multiple aetiologies and substance intoxication each respectively. In only 33(66%) cases in consultation liaison group patients had delirium secondary to other medical conditions. As per DRS-R98 Scale, mean severity score was found to be statistically significant (p<0.05) in consultation liaison group as compared to emergency department group (p> 0.05). CONCLUSION: Delirium is multifactorial aetiological disease, with variable but preventable outcome. Approach should be aimed at finding the treatable causes to reduce morbidity and mortality. PMID- 27656536 TI - Cognitive Behaviour Therapy for Anxiety and Depression among People Undergoing Haemodialysis: A Randomized Control Trial. AB - INTRODUCTION: Chronic Kidney Disease (CKD) is becoming a major public health problem worldwide. The very diagnosis of CKD brings a plethora of psychological problems that adds to the agony of the debilitating illness. Financial difficulties apart from the excruciating physical burden of the disease, owing to series of psychosocial issues. Anxiety and depression are two major concerns that to be managed effectively to sustain the life of people undergoing Haemodialysis. AIM: The study aimed at finding the effect of Cognitive Behaviour Therapy (CBT) on anxiety and depression among people undergoing haemodialysis. MATERIALS AND METHODS: An experimental approach with Randomized controlled trial design was adopted for the study. The instruments used for data collection were Background Proforma and Hospital Anxiety and Depression Scale (HADS). A total of 150 subjects undergoing haemodialysis in a tertiary care hospital of South Karnataka were screened for inclusion and exclusion criteria and 80 participants were recruited for the study. Through computerized block randomization 40 each were allotted to experimental and control groups whereas 33 and 34 respectively in both the groups completed the study. CBT, a structured individual therapy of cognitive, behavioural and didactic techniques, with 10 weekly sessions each was administered to the experimental group. Non-directed counseling, a psychological intervention with ten weekly sessions of individual counseling was given to the control group. RESULTS: The findings of the study revealed that there was a significant reduction of mean anxiety (F=76.739, p=0.001) and depression (F=57.326, p= 0.001) in the experimental group when compared with the control group. CONCLUSION: Researchers concluded that CBT can be effectively utilized for people undergoing haemodialysis in order to obtain control over their negative thoughts thereby reducing anxiety and depression. PMID- 27656537 TI - Multiple Meningioma in a Patient of Bipolar Disorder: The Dilemma of Detecting Structural Brain Lesions in the Backdrop of a Long Standing Psychiatric Illness. AB - Multiple meningioma often can be clinically silent and may present with only psychiatric symptoms. We report a case of 43-year-old, right handed woman with a 23 year history of long standing bipolar affective disorder, who presented with a mixed episode with psychotic symptoms which did not respond to usual treatment and was further complicated with a different set of symptomatology. MRI brain revealed multiple dural based mass lesions identified to be multiple meningiomas. Patient's symptoms improved after gamma knife stereotactic radiosurgery for the multiple meningioma. Our finding illustrates the need to assess for brain lesions in presence of atypical symptoms, along with unresponsiveness to traditional management with psychotropic medications in patients with bipolar affective disorders. PMID- 27656538 TI - Evaluation of Placental Extracts as an Adjuvant Therapy to Phenol in Treatment of Idiopathic Guttate Hypomelanolsis. AB - INTRODUCTION: Idiopathic Guttate Hypomelanolsis (IGH) macules are hypo pigmented lesions occurring due to decreased functioning of melanocytes due to photosensitivity or persistent irritation of skin in middle aged and elderly. AIM: To find out the efficacy of placental extracts when used as an adjunct with 88% phenol for the treatment of IGH macules. MATERIALS AND METHODS: A total of 40 patients were randomly divided into two groups (n=20 in each group), viz group P, (the control group, treated with only 88% phenol) and Group PP (study group, treated with Placental extracts along with 88% phenol). Spot peeling was done with 88% phenol in both the groups while group PP was advised to use placental extract at night for 3 months. Patients of both groups were assessed both subjectively and objectively after every session and at the end of 3 months of initiation of therapy. The statistical analysis was done using Chi-square test, Z test and a p-value<0.05 was considered significant. RESULTS: Both the groups showed significant re-pigmentation of lesions i.e., 76.8% in group P and 79.1% in group PP; whereas, what group PP had shown was non- significantly (p=0.8203) better as compared to group P. CONCLUSION: The clinical and patient acceptability of phenol along with the placental extracts as an adjuvant was better with similar results. Hence, the use of placental extract is recommended along with phenol in IGH lesions. PMID- 27656539 TI - Palmoplantar Dermatoses- A Clinical Study of 300 Cases. AB - INTRODUCTION: Dermatoses affecting palms and soles are among the most difficult of all dermatological therapeutic problems. Many previous studies have focused on the specific diseases of palmoplantar dermatoses. However, none of them have included a comprehensive study of palmoplantar dermatoses. AIMS: To study the epidemiological aspects like age distribution, sex distribution, the dermatoses affecting the palms & soles and the frequency of involvement of palms, soles or both palms & soles, in patient with palmoplantar dermatoses. MATERIALS AND METHODS: This cross sectional study was conducted in the Department of Dermatology between October 2011 to September 2013. First 300 cases attending the department of dermatology primarily with complaints pertaining to palms and soles were enrolled in the study. After taking consent a detailed history and clinical examination pertaining to the aim of the study was recorded and analysed, which included inspection of morphology and distribution of lesions and palpation of any swelling. Direct microscopic examination of scrapings, wet mounted with 10% potassium hydroxide was done for cases with scaly lesions. Those who had a pustule, gram staining was done. Patch testing using Indian Standard Battery Series was done for those cases of eczema. A sample for biopsy was taken when diagnosis could not be arrived clinically, and subjected to histopathological examination. RESULTS: In our study of 300 patients with palmoplantar dermatoses, 164 were females and 136 were males, the ratio observed being 1.2:1. The peak incidence was found in the age group 21-30 years, with 41 females (25%) and 35 males (25.7%). Most frequently affected individuals in this study were housewives (30%). The most common five diseases of palmoplantar dermatoses were palmoplantar psoriasis (20.7%), moniliasis (19%), palmoplantar hyperhidrosis (7%), keratolysis exfoliativa (6%) and pitted keratolysis (6%). Majority of patients had involvement of both palms and soles (44.3%) as compared to patients with involvement of only palm (28%) and only sole (27.3%). The commonest palmoplantar dermatoses with only palm involvement was keratolysis exfoliativa (16.7%), with only sole involvement was moniliasis (41%) and with both palms and soles involvement was palmoplantar psoriasis (41.4%). Associated nail changes were seen in 80 cases (26.6%), with maximum incidence in palmoplantar psoriasis (62.5%). Associated dermatological conditions were observed in 43 patients (14.3%). CONCLUSION: Palmoplantar dermatoses are frequently encount-ered in the dermatologic field. Further investigation with a wider and larger population is necessary to understand the epidemiology, based on which accurate diagnosis and proper treatment could be achieved. PMID- 27656540 TI - Immunohistochemical Expression of Leptin in Non Melanoma Skin Cancer. AB - INTRODUCTION: Obesity in adults is associated with numerous health disorders including some forms of cancer. Various epidemiological studies have found a link between excess adiposity and malignant melanoma; however, the association with non melanoma skin cancer is questionable. Leptin is a hormone produced mainly by the adipose tissue and its serum level may reflect body mass index. Leptin is reported to promote proliferation and angiogenesis and deregulate apoptosis, therefore facilitates the process of carcinogenesis. AIM: The current study tried to assess leptin localization and expression in non melanoma skin cancer to verify its possible role in pathogenesis of this cancer. MATERIALS AND METHODS: This study was carried out on 13 Basal Cell Carcinoma (BCC) cases and 14 Squamous Cell Carcinoma (SCC) cases together with 19 normal skin biopsies as a control group using immunohistochemical method. RESULTS: Leptin was expressed in 52.6% of the normal epidermis with pure cytoplasmic and both cytoplasmic and nuclear staining patterns. All cases of SCC (100%) and two cases of BCC (15.4%) showed leptin expression in tumour cells whereas nuclear expression was in favour of SCC. Stromal expression of leptin was seen in both SCC (57.1%) and BCC (38.5%) without significant differences. Percentage of leptin expression by tumour cells in SCC showed positive linear correlation with tumour size (p=0.02) and microvessel density (p=0.000). Stromal expression of leptin in SCC was associated with large tumour size (p=0.04), advanced stage (p=0.01) and tumours arising in sites other than head and neck (p=0.01). CONCLUSION: Leptin could have a more important role in pathogenesis of cutaneous SCC rather than BCC that may reflect the trivial role of obesity in induction of BCC. The expression of leptin by tumour and stromal cells of SCC could co-operate in its progression by promoting angiogenesis with subsequently acquiring large tumour size and then advanced stage. PMID- 27656541 TI - Could Topical Minoxidil Cause Non-Arteritic Anterior Ischemic Optic Neuropathy? AB - Minoxidil hair formulation is commonly used for the treatment of male or female androgenic alopecia. Minoxidil is a Health Canada and US FDA-approved medication for hair loss in men and women. The drug is marketed as 2% and 5% topical solutions. This over-the-counter product is considered safe, but should be used with caution. Furthermore, minoxidil is an orally active vasodilator for treatment of severe hypertension. Typical side effects of minoxidil are faster heart rate, augmented heart function and stroke volume (which can be associated with reduced vascular resistance upon baroflex stimulus), retained sodium and water and abnormal hair growth. The most common adverse reactions of the topical formulation are limited to irritant and allergic contact dermatitis on the scalp. Herein, we report a non-arteritic anterior ischemic optic neuropathy caused by topical 5% minoxidil treatment that was resolved after discontinuation of minoxidil. PMID- 27656542 TI - Retinol Binding Protein 4 in Non Obese Psoriatic Cases. PMID- 27656543 TI - Retrospective Analysis of Efficacy and Toxicity of Hypo-fractionated Radiotherapy in Breast Carcinoma. AB - INTRODUCTION: The conventional dose fractionation of adjuvant radiotherapy (RT) to whole breast is 45-50 Gy in 25 fractions as 1.8-2.0-Gy per fraction. Lumpectomy cavity with a 1.5-2-cm margin receieves additional 10- 16 Gy doseas boost. Alternative dose fraction schedules used in various randomised trials have established the role of hypofractionated radiotherapy (HRT) in early breast cancer. HRT allows time and cost saving thus better patient compliance. However the efficacy and toxicity of HRT in locally advanced breast cancer is still under evaluation. AIM: To study the toxicity and efficacy of Hypofractionated Radiotherapy (HRT) as compared to Conventional Radiotherapy (CRT) in breast cancer at our centre. MATERIALS AND METHODS: A retrospective analysis of breast cancer patients treated between October 2012- September 2014 with adjuvant radiation therapy as CRT or HRT. The data of these patients was retrieved and analysed regarding demographic profile, stage at presentation, pathological type, extent of surgery, chemotherapy, efficacy and toxicity of HRT. The toxicity assessment was done as per RTOG toxicity criteria. The data were analysed using SPSS software version 20.0. RESULTS: A total of 100 patients with carcinoma breast who received radiotherapy over two years were analysed. Age ranged from 18 90 years, mean 49.15 +/- 12.7 years. Fifty-five patients were post-menopausal, predominant clinical feature was painless lump in the breast (98%). Early stage (Stage I and II) constituted 41%, locally advanced disease in 59%. Modified radical mastectomy was done in 75%, breast conserving surgery in 25%. A 56 patients received HRT and 44 were treated with CRT. The most common acute toxicity was skin grade I. An 18% patients in HRT arm and 30% patients in conventional arm developed grade II skin toxicity (p=0.23). Dysphagia grade I was seen in 10% cases in CRT arm and 12% in HRT arm. The median follow-up period was 11.3 months with 2 loco-regional failures in each arm. CONCLUSION: HRT seems to be equally efficacious and no more toxic than CRT in carcinoma breast even in unselected sub-group of patients. PMID- 27656544 TI - Diagnostic Utility of PAX5 in Hodgkin and Non-Hodgkin Lymphoma: A Study from Northern India. AB - INTRODUCTION: PAX5 is an immunomarker of B-cell origin and useful in the diagnosis of lymphoma. There is hardly any study on PAX5 expression in Indian patients with lymphoma. AIM: To evaluate the diagnostic utility of PAX5 as an adjunct immunohistochemical marker in the diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL). MATERIALS AND METHODS: Immunohistochemistry was performed against CD20, CD3, CD15, CD30, and PAX5 on formalin fixed paraffin embedded tissue of 71 cases of lymphoma and CD20, CD3 and PAX5 in control samples of reactive lymph nodes. Frequency, mean values, and percentage were calculated. Fisher's-exact test and test for analysis of variance were applied. RESULT: For 24 cases of HL and 47 cases of NHL, the mean age of patients was 17.6+/-14.8 years and 44.1+/-21.6 years, respectively. The male: female ratio for both HL and NHL were 1.7:1. Among NHL cases, the numbers of B-cell and T-cell types were 39/47 (83%) and 8/47 (17%), respectively. In comparison to control samples, PAX5+ expression was seen in 23/24 (95.8%) cases of HL (p=1.000) and 32/39 (82%) cases of B-NHL (p=0.0834). All the cases of T-NHL showed negative expression of PAX5 (p<0.0001). Analysis of variance between NHL, HL and control samples was statistically significant (p<0.0001). CONCLUSION: PAX5 staining between control samples and cases of classical HL and B-NHL was statistically not significant, whereas, statistically significant difference was observed with T-NHL. Thus, PAX5 may be used as an adjunct marker in the diagnosis of classical HL and B-NHL. PMID- 27656545 TI - Clinicopathological Profile and Outcomes of Follicular Dendritic Cell Sarcoma of the Head and Neck Region - A Study of 10 Cases with Literature Review. AB - INTRODUCTION: Follicular Dendritic Cell Sarcomas (FDCS) are rare disorders of the lymph node and soft tissues. Accurate characterization of these neoplasms is important in planning optimal treatment given its potential for recurrence and metastasis. AIM: To analyse the clinicopathological profile and outcomes of a series of 10 cases of follicular dendritic cell sarcoma arising in the head and neck region diagnosed at our regional cancer centre. MATERIALS AND METHODS: A series of 10 cases of FDCS of the head and neck region from the hospital registry of head and neck cancers diagnosed between 2007 and 2013 were collected and analysed retrospectively. Clinical details, pathologic features, immuno phenotypic profile, treatment approach and outcomes over a period of 5 years were noted. The Recurrence Free Survivals (RFS) of all the patients were recorded. RESULTS: The median age of the patients was 57 years and the mean age was 50.9 years. Male: female ratio was 7:3. In eight of the 10 patients, the tumours were located in the tonsils. All the tumour cells showed diffuse cytoplasmic CD21 and CD23 positivity by IHC. All the 10 cases underwent surgical excision of the tumour and three cases underwent additional neck dissection for cervical lymph node enlargement. All the patients with high grade tumours were uniformly managed with Tri-modality treatment (Surgery followed by radiotherapy and chemotherapy). The overall recurrence rate was 70%. The mean and median recurrence free survival was 39.6 and 44 months, respectively. Two of the three patients who remained recurrence free at the end of the 60 months had low grade tumours. CONCLUSION: Early recognition of follicular dendritic cell sarcomas requires a high index of suspicion and bi-modality or tri-modality treatment may cure a subset of low and high grade tumours respectively and prolong recurrence in a large subset of patients. Surgery is the mainstay and the definitive modality of treatment; the advantages and benefit of adjuvant radiotherapy and chemotherapy are yet to be established. Tri-modality management may have a role in high grade patients which needs to be substantiated in future studies. PMID- 27656546 TI - Clinical Measurement of Maximum Mouth Opening in Children of Kolkata and Its Relation with Different Facial Types. AB - INTRODUCTION: Maximal opening of mouth is described as the greatest distance between incisal edge of maxillary central incisor to the incisal edge of mandibular central incisor, when the mouth is opened as wide as possible painlessly or as the inter incisal distance plus the overbite. Clinical measurement of normal range of Maximum Mouth Opening (MMO) in children is an important diagnostic criterion for evaluation of stomatognathic system, especially for those with temporomandibular and neurogenic dysfunctions. AIM: To determine the correlation of maximal mouth opening with age, sex, height, body weight and different facial types. MATERIALS AND METHODS: The study was a cross sectional study which was conducted on 434 children, who were randomly divided into three groups based on their age: Group I- children of age 6 to 8 years, Group II- children of age 8.1 to 10 years, Group III- children of age 10.1 to 12 years. For each child, the examiner took three readings of MMO in millimeters (mm) and the mean of the three readings was considered. Age, sex, standing height, body weight and facial type of each child were also recorded simultaneously. Pearson correlation was used to determine the relationship between the different parameters. p-value <0.05 was the bench mark for statistical significance in the analysis. Descriptive and inferential analysis was done for the data using SPSS version 20.0. (SPSS 20, inc.; Chicago). RESULTS: The estimated average MMO measured for girls and boys in the age range of 6-8 years, with a total sample size of 139, was 41.14 +/- 4.29 mm and 42.16 +/- 3.98mm respectively in euryprosopic face type. In leptoproscopic face type, it was 42.12 +/- 4.54mm and 43.76 +/- 3.80 mm in girls and boys respectively. In mesoproscopic face type, MMO measured was 41.77 +/- 4.09mm and 42.51 +/- 3.95 mm in girls and boys respectively. The estimated average MMO measured for girls and boys in the age range of 8.1-10 years, with a total sample size of 143, was 44.42+4.69mm and 43.30 +/- 4.11 mm in euryprosopic face type. In leptoproscopic face type, it was 43.02 +/- 3.92mm and 46.29 +/-3.09mm in girls and boys respectively. In mesoproscopic face type, MMO measured was 42.50 +/-4.32 and 42.80 +/- 5.16 mm in girls and boys respectively. The estimated average MMO measured for girls and boys in the age range of 10.1-12 years, with a total sample size of 152, was 44.63 +/- 5.28 mm and 45.80 +/- 5.18 mm respectively in euryprosopic face type. In leptoproscopic face type, it was 45.76 +/- 4.98 mm and 46.28 +/- 4.68 mm in girls and boys respectively. In mesoproscopic face type, MMO measured was 45.32 +/- 5.80 mm and 46.03 +/- 5.86 mm in girls and boys respectively. CONCLUSION: There was a significant difference in MMO between males and females; with males having higher values in all age groups. MMO is seen to increase with age in a statistically significant manner. Significantly increased value of MMO was observed in leptoproscopic face type in comparison to euryproscopic and mesoproscopic face type for each age group. PMID- 27656547 TI - The Hormonal Fingerprints and BMI: Implications for Risk Factors in Dental Caries and Malocclusion. AB - INTRODUCTION: The hormonal fingerprint is the ratio between 2(nd) and 4(th) digit lengths. It was evidenced in the medical scenario that it can be used as an indirect marker in many diseases like Coronary Heart Disease (CHD) and metabolic syndromes. As far as dentistry is concerned very few studies in the literature have been done to evaluate the influence of hormonal fingerprint on oral health, thus provoking us to formulate new method for predicting dental caries and malocclusion and its association with Body Mass Index (BMI). AIM: The purpose of this retrospective study was to highlight the role of new biological marker Hormonal fingerprints in the early detection of malocclusion, caries, the influence of BMI on malocclusion and caries. We also attempted to study the correlation of BMI with hormonal fingerprints. MATERIALS AND METHODS: A total of 300 children were randomly selected from both sexes of age group 10-15 years. The hormonal fingerprint was made by measuring the length ratio of the index and ring finger with the help of digital Vernier caliper. Anthropometric measures (weight in kilograms and height in metres) for the calculation of BMI were recorded. Caries assessment was done using standard mouth mirrors and Community Periodontal Index probes. DMFT index was followed for assessment of caries according to the WHO assessment form, 1997. Occlusal characteristics of the children evaluated were molar relation, anterior and posterior cross bite, open bite, deep bite, lower anterior crowding. All the factors were recorded by two investigators. RESULTS: The results of the study showed that majority of the children among study population were having 2D:4D <1. The rate of occurrence of malocclusion was increasing with increase in the value of 2D:4D ratio with a statistically significant p-value of <0.001. Higher BMI values were associated with normal occlusal conditions (p= 0.041) and lower 2D:4D ratio (p= 0.037). High caries experience was noticed in children with malocclusion (p= 0.027) which further influences the caries susceptibility. Pearson's correlation test, t-test and ANOVA were used in the study for statistical analysis using SPSS software. CONCLUSION: This study confirms the impact of hormones on incidence of malocclusion, BMI which in turn influences the caries index and could be used as an early predictor. PMID- 27656548 TI - Cone Beam Computed Tomography- An Effective Tool in Detecting Caries Under Fixed Dental Prostheses. AB - INTRODUCTION: Caries under restorations is the most common reason for re treatment and replacement in restorative failures. To avoid failures of fixed dental prostheses, it is important to diagnose caries under it earlier. Without image degradation and metal artifacts, Cone Beam Computed Tomography (CBCT) can be the solution to detect caries without removing fixed dental prostheses. AIM: The aim of this study was to determine the efficacy of CBCT in detecting caries under fixed dental prostheses. MATERIALS AND METHODS: Each specimen was scanned with CBCT for evaluation of secondary caries under fixed prostheses. Exposure parameters were 60 kVp and 3mA. Field of View (FOV) used was 8cm X 8cm. According to International Caries Detection and Assessment System (ICDAS) criteria, six Grade 6 carious extracted teeth were selected. All teeth were prepared with four different specimens - full metal, metal-ceramic, full ceramic and metal-acrylic crowns for each tooth. Each specimen was scanned by CBCT. T-test was performed for mean gray value differences between caries and noncaries regions of each material. Gray values were recorded and evaluated for different parameters using two-way analysis of variance. RESULTS: Significant differences were found with respect to material (full metal, metal-ceramic, full ceramic and metal-acrylic) and situation (caries/noncaries) (p<0.001). There were no significant differences with respect to location (anterior or posterior). Mean gray values of caries and noncaries regions were found to be different for each material. CONCLUSION: CBCT can be used as a post-treatment diagnostic technique for detecting caries under fixed prostheses without removing it. PMID- 27656549 TI - Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma. AB - INTRODUCTION: More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. AIM: The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. MATERIALS AND METHODS: Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann Whitney U test. RESULTS: The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. CONCLUSION: Mast cells favour malignant transformation and can be used as indicators of disease progression. PMID- 27656550 TI - An Invitro Evaluation of Antimicrobial Efficacy and Flow Characteristics for AH Plus, MTA Fillapex, CRCS and Gutta Flow 2 Root Canal Sealer. AB - INTRODUCTION: Cleaning and shaping of root canal does not guarantee complete disinfection of the canal, regardless of the systems and techniques used for this purpose. Therefore, it becomes mandatory for the endodontic filling materials to have a good antimicrobial potential especially against E. faecalis. This research was aimed therefore to evaluate the antibacterial efficacy and flow properties of different root canal sealers. AIM: To study invitro antimicrobial activity and flow characteristics for Resin based (AH Plus), Mineral Trioxide Aggregate based (MTA Fillapex), Calcium hydroxide based (CRCS) and Flowable Gutta-Percha (Gutta Flow 2) endodontic sealers on Enterococcus faecalis. MATERIALS AND METHODS: Enterococcus faecalis ATCC 29212 was used to test antibacterial potential of sealers by Agar diffusion test (ADT) and Direct Contact Test (DCT). ADT was performed by punching the sealers on a well of 4*6mm diameter on Muller Hinton agar plates. These plates were inoculated with standard suspension of E. faecalis and the zone of inhibition was measured at 24 hours and after 7 days. All the sealers were prepared in accordance with the manufacturer's recommendations. Flow of sealers was measured according to ADA specification no. 57. RESULTS: All sealers showed antibacterial activity against E. faecalis except Gutta Flow 2. At 24 hours, zone of inhibition was highest in Calcibiotic Root Canal Sealer (CRCS) and lowest in AH Plus. After 7 days the zone of inhibition decreased in AH plus, CRCS and MTA Fillapex. DCT showed a significant lower number of organisms in AH Plus, CRCS and MTA than controls at both the time intervals. Gutta Flow 2 did not show any significant antimicrobial action. Maximum and minimum flow was shown by AH Plus and CRCS respectively. CONCLUSION: Highest microbial inhibition was shown by (CRCS), followed by MTA Fillapex and AH Plus. Gutta Flow 2 did not show any inhibition of E. faecalis by ADT. Maximum reduction in antibacterial property with time against E. faecalis was seen with AH Plus. Maximum flow was shown by AH Plus and minimum by CRCS. PMID- 27656552 TI - Effect of Alendronate with beta - TCP Bone Substitute in Surgical Therapy of Periodontal Intra-Osseous Defects: A Randomized Controlled Clinical Trial. AB - INTRODUCTION: Alendronate (ALN), an aminobisphosphonate, inhibits osteoclastic bone resorption and also stimulates osteogenesis. Beta-Tricalcium Phosphate (beta TCP) is an osteoconductive graft material which provides a scaffold for bone formation and also a widely used drug delivery vehicle for growth factors and antibiotics. Drug delivery vehicles, like beta-TCP, improve the potency of the drugs by specific local site delivery of the drug, optimal release characteristics and easy handling. AIM: The aim of the this study was to evaluate the bone formation potential of 400MUg ALN delivered in beta-TCP in the treatment of periodontal intra-osseous defects. MATERIALS AND METHODS: Thirty patients with periodontal defects were randomly assigned to 400MUg ALN + beta-TCP + Saline (test) group and beta-TCP + Saline (active-control) group. Clinical parameters like Clinical Attachment Level (CAL) gain, Probing Depth (PD) reduction, post operative Gingival Recession (GR) were assessed from the baseline, 3 months and 6 months recordings. Radiographic parameters like Linear Bone Growth (LBG), Percentage Bone Fill (%BF), and change in alveolar crest height (ACH) were assessed from baseline and 6 months radiographs. RESULTS: Mean measurements in the ALN test group for CAL gain (3.4 +/- 0.74 mm), PD reduction (4.33 +/- 0.82 mm), LBG (2.88 +/- 0.88 mm), and %BF (51.98 +/- 15.84%) were significantly greater with a p-value <0.05 compared to the mean measurements of CAL gain (2.20 +/- 0.86 mm), PD reduction (3.20 +/- 1.15 mm), LBG (1.70 +/- 0.39 mm), and %BF (30.35 +/- 6.88%) of the control group. There was mild alveolar crestal apposition (0.32 +/- 0.68 mm) in the ALN test group and mild alveolar crestal resorption (-0.24 +/- 0.40 mm) in the control group. CONCLUSION: 400MUg ALN combined with beta-TCP bone graft material was effective in improving soft tissue parameters, inhibiting alveolar crestal resorption and enhancing bone formation, compared to beta-TCP alone. PMID- 27656551 TI - Association of Oral Candida albicans with Severe Early Childhood Caries - A Pilot Study. AB - INTRODUCTION: In early childhood, children are more susceptible to opportunistic microbial colonization in the oral cavity due to immature immune system and not fully established micro flora. The current literature proposes a probable role of Candida albicans, a fungus in the etiopathogenesis of dental caries. AIM: This study was conducted to compare the Candida albicans count in children with severe early childhood caries and caries free children. MATERIALS AND METHODS: A cross sectional study was conducted in 40 randomly selected healthy children between 12 to 71 months of age, who were divided into two groups based on the caries experience as Severe Early Childhood Caries (SECC) (dmfs >=4) and caries free (dmfs = 0). The caries experiences (dmfs index) of the 40 children were recorded using visible light and diagnostic instruments. A 2ml sample of unstimulated whole saliva collected from the children was transported to the microbiology laboratory in universal containers and evaluated for Candida albicans count using the selective media. The data was statistically analyzed using SPSS software 17.0. RESULTS: Candida albicans was found in both the SECC group and caries free group. Median Candida albicans of the SECC group was numerically greater than the caries free group and this difference was highly statistically significant (p=0.012). CONCLUSION: In this present cross-sectional study, we found a 100% prevalence of Candida albicans in the saliva of the study children. There was a highly significant increase in Candida albicans count in SECC children compared to the caries free children. PMID- 27656553 TI - Graphical Assessment Technique (GAT) - An Objective, Comprehensive and Comparative Hand Hygiene Quantification Tool. AB - INTRODUCTION: There has been a profound leap in developing countries in sectors of human development but it falls short of millennium development goals. Diarrhoea, respiratory infections are primary cause of child deaths around the world due to improper hygiene practice. There is lack of systematic objective analysis, follow-up and quantification of hand hygiene guidelines. So, there is an urgent requisite of a tool to assess the same. AIM: To conduct a pilot test for assessing the efficacy of Graphical Assessment Technique (GAT) in objectively evaluating and comparing intervention based hand hygiene among students of National Association of Blind School (NABS) and a government school. MATERIALS AND METHODS: GAT was used to assess the baseline and post-intervention improvement of 80 students considered for the study. Data was analyzed using SPSS software version 20.0 and was subjected to quantitative analysis and parametric tests. RESULTS: Non-significant difference (p>=0.05) was found at baseline and immediate post-intervention on percentage mean scores of blind school students and government school student, while government school children also showed non significant difference at one week. Significant difference (p<=0.05) was found at baseline, post-intervention one week and post-intervention one month for blind school children along with baseline and post-intervention mean percentage scores for government school children. CONCLUSION: The primary agenda behind the study was to test a tool which can objectively evaluate, quantify and compare the follow-up of hand hygiene guidelines and aid in better hand hygiene promotion. PMID- 27656554 TI - Evaluation of Anxiety Induced Cardiovascular Response in known Hypertensive Patients Undergoing Exodontia - A Prospective Study. AB - INTRODUCTION: Anxiety towards exodontic procedures is a common occurrence in dental practice. In hypertensive patients this anxiety induced stress may have an effect on cardiovascular system which may be clinically significant. AIM: To evaluate the cardiovascular changes in hypertensive patients that may manifest following anxiety induced stress in patients undergoing exodontic procedures under local anaesthesia. MATERIALS AND METHODS: Eighty known hypertensive patients under medication reporting to Department of Oral and Maxillofacial surgery, Dayananda Sagar College of Dental Sciences Bangalore, Karnataka, India for extraction of teeth were taken up for the study. Anxiety was measured before local anaesthetic delivery using Amsterdam Pre-operative Anxiety and Information Scale (APAIS). Cardiovascular response data including blood pressure, heart rate, pulse rate, oxygen saturation and electrocardiographic changes were measured pre operatively, immediately after local anaesthesia administration and Post operatively at five, ten and fifteen minutes interval. Kruskal-Wallis test was used to compare continuous variables before and after the injection of local anaesthesia including heart rate, pulse rate, oxygen saturation, and blood pressure. Repeated-measures analysis of variance (ANOVA) was used to analyse the significance of changes in heart rate, pulse rate, blood pressure, and oxygen saturation over time between groups.Chi-square test was used to analyse the significance of electrocardiographic changes. RESULTS: The results revealed that the mean anxiety score before administration of local anaesthetic was 9.91(S.D +/ 2.9) with a range 4-20. Severe preoperative anxiety (<12) was associated with significantly increased heart rate, pulse rate, systolic blood pressure. At the pre-injection phase the mean values were systolic blood pressure (130.72+/-9.2), diastolic blood pressure (81.6+/-7.7), heart rate (72.7+/-11.9) and oxygen saturation (95.2+/-1.9). These values were increased immediately after local anaesthetic delivery and this relation was statistically significant for all parameters except oxygen saturation. Electrocardiographic abnormalities were found before and after injection of local anaesthetic (p>0.001). One patient showed right bundle branch block pattern. CONCLUSION: Dental anxiety impacts the effects of delivery of local anaesthesia on blood pressure, heart rate, pulse rate and electrocardiograph and is significantly associated with the increase in systolic blood pressure, heart rate, pulse rate and changes in electrocardiograph. Thus, present study supported that increased anxiety in hypertensive patients who underwent extraction is associated with cardiovascular changes. PMID- 27656555 TI - Assesment of Correlation of Herpes Simplex Virus-1 with Oral Cancer and Precancer A Comparative Study. AB - INTRODUCTION: Most common malignant neoplasm in the oral cavity is squamous cell carcinoma. Herpes simplex virus (HSV) may enhance the development of oral carcinoma in individuals who are already at increased risk of the disease because of tobacco consumption and cigarette smoking and so must be considered as a possible etiologic agent in oral cancer and precancer. AIM: To assess and compare the correlation of HSV-1 in oral cancer and precancerous lesions/conditions with healthy subjects. MATERIALS AND METHODS: The study comprised of 150 subjects who were divided into three groups as oral cancer, precancer and control group. Their blood samples were collected and were tested for HSV-1 IgG antibody level, using 'Herpe Select-1' ELISA kit. RESULTS: There was statistically insignificant difference between the HSV-1 IgG level in cancer and precancer but statistically significant difference was found between the HSV-1 IgG level among control group and cancer/precancer. CONCLUSION: The present study clearly indicates that quantitative estimation of IgG antibody against HSV-1 in cancer/precancer patients will give the clue in the etiology of cancer or precancer. However, further studies with a large sample size should be carried out to determine the role of HSV-1 in etiology of oral cancer and precancer. PMID- 27656556 TI - Evaluating the Type of Light Transmittance in Mono Crystalline, Poly Crystalline and Sapphire Brackets- An Invitro Spectrofluorometer Study. AB - INTRODUCTION: Most of the patients seek orthodontic treatment to improve the smile, which improves the facial profile by means of fixed appliances i.e., brackets and wires. The brackets are of different types like stainless steel and ceramic. Ceramic brackets were considered as aesthetic appliance which was divided into mono-crystalline, polycrystalline and sapphire brackets. The light transmittance might influence the degree of curing adhesive material in mono crystalline, polycrystalline and sapphire brackets. AIM: The aim of the present study was to evaluate the translucency and intensity of three different aesthetic brackets (mono crystalline, poly crystalline and sapphire ceramic brackets) and to determine their influence on shear bond strength of the brackets. The adhesive remnant index was also measured after debonding of the brackets from the tooth surface. MATERIALS AND METHODS: Twenty six samples each of monocrystalline, polycrystalline and sapphire brackets (total 78 ceramic brackets) were used for the study. The bracket samples were subjected to optical fluorescence test using spectrofluorometer to measure the intensity of the brackets. Seventy eight extracted premolar teeth were procured and divided into 3 groups. The brackets were then bonded to the tooth using Transbond XT (3M Unitek) light cure composite material and cured with new light cure unit (Light Emitting Diode) of wood pecker company (400-450nm) for 30 seconds, and these samples were subjected to shear bond strength test with Instron Universal Testing Machine (UNITEK-94100) with a load range between 0 to 100 KN with a maximum cross head speed of 0.5mm/min. ARI (Adhesive Remnant Index) scores were evaluated according to Artun and Bergland scoring system using stereomicroscope at 20x magnification. RESULTS: The light absorption values obtained from spectrofluorometeric study were 3300000-3500000 cps for group 1 (monocrystalline ceramic brackets), 6000000-6500000 cps for Group 2 (polycrystalline ceramic brackets) and 2700000 -3000000 cps for Group 3 (sapphire ceramic brackets) i.e., Group 2 showed the highest light absorption and the least translucency followed by groups 1 and 3. Shear bond strength results were 2.4 mpa, 1.9 mpa and 3.6 mpa for groups 1,2 and 3 respectively. Superior shear bond strength was recorded in group 3 (sapphire ceramic brackets). ARI results showed that group 3 had increased bond between bracket adhesive interfaces when compared to the other 2 groups. CONCLUSION: From this study, it has been concluded that sapphire ceramic brackets (Group 3) was superior in translucency and shear bond strength followed by monocrystalline and polycrystalline ceramic brackets. PMID- 27656557 TI - Effect of Various Finishing Procedures on the Reflectivity (Shine) of Tooth Enamel - An In-vitro Study. AB - INTRODUCTION: Reflectivity of an object is a good parameter for surface finish. As the patient evaluates finishing as a function of gloss/reflectivity/shine an attempt is made here to evaluate changes in surface finish with custom made reflectometer. AIM: The aim of the present study was to study the effect of various procedures during orthodontic treatment on the shine of enamel, using a custom made reflectometer. MATERIALS AND METHODS: Sixty one extracted premolars were collected and each tooth was mounted on acrylic block. Reflectivity of the teeth was measured as compared to standard before any procedure. One tooth was kept as standard throughout the study. Sixty teeth were acid etched. Reflectivity was measured on custom made reflectometer and readings recorded. Same procedure was repeated after debonding. Then 60 samples were divided into three groups: Group 1 - Tungsten Carbide, Group 2 - Astropol, Group 3- Sof-Lex disc depending upon the finishing method after debonding and reflectivity was measured. RESULTS: The mean percentage of reflectivity after acid etching was 31.4%, debonding 45.5%, Tungsten carbide bur finishing (Group 1) was 58.3%, Astropol (Group 2) 72.8%, and Sof-Lex disc (Group 3) 84.4% as that to the standard. There was statistically very highly significant (p<0.001) difference in reflectivity restored by the three finishing materials in the study. Thus, the light reflection was better in Group 3> Group 2> Group 1. CONCLUSION: The primary goal was to restore the enamel to its original state after orthodontic treatment. The methods tested in this study could not restore the original enamel reflectivity. PMID- 27656558 TI - Evaluation of Histomorphometric Changes in Tissue Architecture in Relation to Alteration in Fixation Protocol - An Invitro Study. AB - INTRODUCTION: Preparation of good tissue specimens for microscopy requires complete fixation. No ideal fixative has been found till date, with every fixative showing advantages and disadvantages. Appropriate fixation is required to maintain clear and consistent morphologic features for histologic examination. Pathologists mostly examine formalin fixed tissue sections and are less used to the morphologic changes induced by other fixatives. Underfixed and overfixed tissue in various fixatives can lead to tissue architectural changes which can affect its diagnostic value. AIM: To assess sectioning ability, staining intensity and microscopic details of tissues kept in different fixatives at different time intervals. MATERIALS AND METHODS: Fresh tissue specimen i.e., goat tongue was collected and its middle-third portion was used for the study purpose. The tissue was grossed into 10 equal pieces and kept in various fixatives (10% Buffered formalin, Carnoy's solution, Absolute ethyl alcohol, Bouin's fluid) for five different time intervals (6, 12, 18, 24 and 30 hours) and normal tissue processing steps were carried out followed by sectioning and staining. During sectioning, sectioning parameter was assessed. Following sectioning, sections were observed under light microscope and were histologically evaluated for staining and microscopic details. To calculate the sectioning parameter Fisher's exact test was used and to assess parameters for staining and microscopic details Mann-Whitney U test was used. RESULTS: According to the study, 10% buffered formaldehyde is considered as a superior fixative under all parameters followed by Bouin's fluid, Carnoy's solution and Absolute alcohol. CONCLUSION: In our study, it was concluded that 10% buffered formaldehyde should be continued as a routine fixative however, other fixatives can be used depending upon the non availability of required fixative or in case of emergencies. Pathologist should be accustomed to histologic and morphologic changes of underfixed and overfixed tissue which can affect its diagnostic value. PMID- 27656560 TI - Stereomicroscopic Evaluation of Sealing Ability of Four Different Root Canal Sealers- An invitro Study. AB - INTRODUCTION: The most commonly used core material for root canal filling is gutta-percha and as the gutta-percha by itself cannot obturate the complete root canal system, owing to its poor sealing properties hence, a sealer is used in combination with root filling material. Sealer is more important than the core obturating material. Sealer plays a secondary role by merely reinforcing (binding or luting) the gutta-percha to the canal walls, however, it is now confirmed that the sealer has a prime role in sealing the canal by blocking the irregularities between the canal space and the core filling material. AIM: To investigate the effectiveness of the apical seal obtained by different sealers used in conjugation with cold lateral condensation technique of obturation using gutta percha under stereomicroscope. MATERIALS AND METHODS: One hundred single-rooted extracted human permanent teeth with a single root canal were used in this in vitro study. The sealers tested were conventional Zinc oxide eugenol sealer, Apexit, AH-Plus and Roekoseal Automix (RSA). The specimens were examined under a stereomicroscope. For the analysis of data Snedocor's F test for the quality of variances among the experimental group and control group (One-Way ANOVA) were employed. RESULTS: The polydimethylsiloxane endodontic root canal sealer RSA provided a significantly better apical seal followed by AH plus and Apexit whereas conventional zinc oxide eugenol showed the lowest sealing ability. CONCLUSION: It was concluded that there were statistically significant differences amongst the experimental groups. The shrinkage related to setting and potential dissolution might risk the proper seal of the root canal leading to treatment failure. PMID- 27656559 TI - Comparative Evaluation of Longevity of Fluoride Release From three Different Fluoride Varnishes - An Invitro Study. AB - INTRODUCTION: Fluoride varnishes play a pivotal role in inhibition of dental caries by increasing remineralization. AIM: To determine the longevity of fluoride release from 3 different fluoride varnishes over a period of time through salivary fluoride estimation. MATERIALS AND METHODS: Twenty four extracted human deciduous anterior teeth were divided into four groups, i.e., ClinproTM XT, Flouritop SR, Flourprotector and Control group. Fluoride varnishes were applied on 3mm x 3mm window on labial surface of the teeth and then the teeth were immersed and stored in artificial saliva. The concentration of fluoride in ppm was measured after 1 week, 1 month, 3 months and 6 months. Fluoride release at each time interval for different groups was statistically analyzed using ANOVA and Post Hoc Tukey's test. RESULTS: Although all the fluoride varnishes released fluoride, with greatest release observed during 1(st) week by Fluoritop SR (66.92+/-16.30ppm), ClinproTM XT Varnish released consistently and substantially more fluoride than Fluoritop SR and Fluorprotector during 6 months analysis (p<0.05). Fluorprotector showed the lowest rate of F release among all the groups compared. CONCLUSION: Over a period of 6 months ClinproTM XT Varnish released consistently and substantially more fluoride than other tested products. PMID- 27656561 TI - Periodontal Health among Non-Hospitalized Chronic Psychiatric Patients in Mangaluru City-India. AB - INTRODUCTION: A substantial section of society constituting the mentally ill and psychiatric patients deserve special attention. Evidence has suggested that psychological factors have contributed to an increase in the susceptibility to periodontal disease. AIM: The aim of the study was to evaluate the gingival and periodontal health of chronically non-hospitalized psychiatric patients in Mangaluru city, India. MATERIALS AND METHODS: Forty one psychiatric patients having chronic psychiatric illness and on neuroleptic medications for a minimum of 2 years were included in the study. The control group consisted of 41 healthy dental patients who were selected to match the study group by age and gender, and for both groups 20 teeth excluding the third molars should be present. Demographic characteristics, dental examination including gingival index and periodontal health according to the community periodontal index were recorded for each patient in both the groups. RESULTS: In the psychiatric patient group (Group A) 47.1% subjects were suffering from schizophrenia and 17.6% subjects were having mood disorder. Gingivitis varied from mild to severe among the patients of both the groups. Bleeding on probing (CPI 1) was recorded in 23.5% in Group A and 14.6% in Group B. Dental calculus (CPI 2) in 38.2% in Group A and 58.5% in Group B of the subjects, 20.6% with at least one 4mm to 5mm pocket (CPI 3), and 17.6% with at least one 6mm pocket (CPI 4). CONCLUSION: The present study underlines a considerable need for prevention and treatment of periodontal disease among chronic psychiatric patients in Mangaluru city. Every effort should be made to increase the awareness of this cohort regarding the importance of oral hygiene practices and on the early diagnosis of periodontal problems. PMID- 27656562 TI - Spectrophotometric Evaluation of the Pulpal Peroxide Levels in Intact and Restored Teeth - An Invitro Study. AB - INTRODUCTION: Hydrogen peroxide (30%) is a commonly used "in office" bleaching agent. Deleterious effects of hydrogen peroxide on the pulp have been observed. AIM: The present study was conducted with the aim to evaluate the penetration of 30% hydrogen peroxide into the pulp chamber through intact teeth and through the surface of teeth, restored with either hybrid composite or Resin Modified Glass Ionomer Cement (RMGIC). MATERIALS AND METHODS: Sixty extracted human maxillary central incisors were selected and divided into six groups. Two groups were restored with hybrid composite resin and two with RMGIC, while two groups were left intact. The teeth with acetate buffer solution in their pulp cavity were then immersed in either 30% hydrogen peroxide or distilled water depending upon the group, for 60 minutes at 37 degrees C. Then horseradish peroxidase and leucocrystal violet were added to the acetate buffer solution present in the pulp chamber after it was transferred to a test tube and the optical density of the resultant blue solution obtained was measured spectrophotometrically. STATISTICAL ANALYSIS: The data obtained were analyzed using one way ANOVA and Student's t test. RESULTS: The data obtained established that hydrogen peroxide penetrated into the pulp from the bleaching agent used. Hydrogen peroxide (30%) showed the highest pulpal peroxide level in teeth restored with RMGIC followed by teeth restored with hybrid composite resin and the least amount of penetration was observed in intact teeth. CONCLUSION: The amount of peroxide penetration into the tooth is more through restored tooth than intact tooth and is also dependant on the type of restorative materials used. PMID- 27656564 TI - Evaluating the Effect of CPP-ACP as a Final Irrigant in Improving the Micro Hardness of Erosive Root Dentin and its Influence on the Bond Strength of Self Etch Resin Sealer - An In-vitro Study. AB - INTRODUCTION: Smear layer removal from the root canal wall involves the use of 17% EDTA and 5.25% sodium hypochlorite, which thereby improves the adhesion of obturating materials to root dentin. But these chemical irrigants have shown to decrease micro hardness, increase roughness, cause erosion and reduce the root dentin fracture toughness. To combat these adverse effects, studies can be focussed on the remineralisation of the erosive root dentin and this novel idea has been utilized in the present study. AIM: To evaluate the micro hardness of erosive root dentin when Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP ACP) was used as a final irrigant and its influence on resin sealer bonding tested by push-out bond strength method. MATERIALS AND METHODS: Sixty extracted maxillary incisors were divided into three groups based on the final irrigation protocol. Group 1-normal saline, Group 2-17% EDTA (Ethylene Diamine Tetraacetic Acid) + 5.25% NaOCl (Sodium Hypochlorite), Group 3 - 17% EDTA + 5.25% NaOCl + CPP ACP; each group was divided into two subgroups. Half the specimens of each group were evaluated for Vicker's micro hardness test after the treatment. In continuation with the above methodology the remaining specimens were tested for push-out bond strength after obturation of the specimens with self etch adhesive resin sealer and conventional 6% gutta percha cones. RESULTS: Micro hardness was statistically analysed using Kruskal Wallis test and push-out bond strength was evaluated using Mann Whitney test and paired t-test. CPP-ACP treated group showed increased micro hardness (p<0.05). There was no statistically significant difference between the push-out bond strength values between group EDTA + NaOCl group and EDTA + NaOCl + CPP-ACP group. CONCLUSION: Within the limitations of this study it can be concluded that, CPP-ACP improved the micro hardness of erosive root dentin and is not affecting its bond strength. Therefore, CPP-ACP may be used before bonding procedures for promoting remineralization of root dentin. PMID- 27656563 TI - Immunohistochemical Localization of Epithelial Mesenchymal Transition Markers in Cyclosporine A Induced Gingival Overgrowth. AB - INTRODUCTION: Cyclosporine, an immunosuppressive agent used in the management of renal transplant patients is known to produce Drug Induced Gingival Overgrowth (DIGO) as a side effect. Several mechanisms have been elucidated to understand the pathogenesis of DIGO. Recently, epithelial mesenchymal transition has been proposed as a mechanism underlying fibrosis of various organs. AIM: The aim of the study was to investigate if Epithelial Mesenchymal Transition (EMT) operates in Cyclosporine induced gingival overgrowth. MATERIALS AND METHODS: The study involved obtaining gingival tissue samples from healthy individuals (n=17) and subjects who exhibited cyclosporine induced gingival overgrowth (n=18). Presence and distribution of E-Cadherin, S100 A4 and alpha smooth muscle actin (alpha-SMA) was assessed using immunohistochemistry and cell types involved in their expression were determined. The number of alpha- SMA positive fibroblasts were counted in the samples. RESULTS: In control group, there was no loss of E Cadherin and a pronounced staining was seen in the all layers of the epithelium in all the samples analysed (100%). S100 A4 staining was noted in langerhans cells, fibroblasts, endothelial cells and endothelial lined blood capillaries in Connective Tissue (CT) of all the samples (100%) while alpha - SMA staining was seen only on the endothelial lined blood capillaries in all the samples (100%). However in DIGO, there was positive staining of E-Cadherin only in the basal and suprabasal layers of the epithelium in all the samples (100%). Moreover there was focal loss of E-Cadherin in the epithelium in eight out of 18 samples (44%). A break in the continuity of the basement membrane was noted in three out of 18 samples (16%) on H & E staining. CONCLUSION: Based on the analysis of differential staining of the markers, it can be concluded that EMT could be one of the mechanistic pathways underlying the pathogenesis of DIGO. PMID- 27656566 TI - Immunohistochemical Detection of p75 Neurotrophin Receptor (p75-NTR) in Follicular and Plexiform Ameloblastoma. AB - INTRODUCTION: Ameloblastoma holds a unique position among benign tumours by its locally destructive and invasive nature. Recently improvised molecular techniques helped researchers to unravel the myth behind such biologic behaviour. Though interesting findings have been delivered, the rhythmic correlation regarding the exact mechanism still remains lacking. Neurotrophins and their receptor mediated pathways play a crucial role in survival, death and differentiation of many neuroectoderm derived cells. With this background, the study has been aimed to investigate the expression of p75-NTR (Neurotrophin Receptor) in follicular and plexiform ameloblastoma. AIM: To analyze the immunohistochemical expression pattern of p75-NTR in ameloblastoma and to compare the immunohistochemical expression pattern of p75-NTR among the histological types of ameloblastoma, follicular and plexiform patterns. MATERIALS AND METHODS: Total 22 ameloblastomas (12 follicular, 10 plexiform) were immuno-stained with anti-human p75-NTR mouse IgG monoclonal antibody and the pattern of staining is statistically analyzed. RESULTS: Only 11 (10 follicular, 1 plexiform) out of 22 ameloblastomas showed immuno-reactivity to p75-NTR. In ameloblastoma, only the peripheral pre ameloblast like tall columnar cells showed reactivity whereas the stellate reticulum-like cells were immuno-negative. The staining pattern was membranous in the immuno-reactive cells. The results were studied with the downstream pathways from the literature and a possible mechanism has been proposed. CONCLUSION: The expression pattern of p75-NTR was found to be more in follicular ameloblastoma than plexiform. PMID- 27656565 TI - Evaluation of Outcome Following Coronectomy for the Management of Mandibular Third Molars in Close Proximity to Inferior Alveolar Nerve. AB - INTRODUCTION: Iatrogenic damage to Inferior Alveolar Nerve (IAN) is a significant risk factor following prophylactic or therapeutic removal of impacted mandibular third molar. The risk to IAN injury increases many fold, when the third molar root overlaps the nerve canal as identified by the radiographic imaging. Various methods like orthodontic assisted extraction, staged removal of tooth or coronectomy have been advocated to reduce the incidence of IAN injury in high risk cases with variable outcome. AIM: The aim of present study was to evaluate the fate of the root (resorbed, exfoliated, covered by bone) after coronectomy or intentional root retention of impacted mandibular 3(rd) molars in patients with high risk for inferior alveolar nerve damage as evaluated by the intra oral periapical radiograph. MATERIALS AND METHODS: Twenty impacted mandibular third molar teeth, in 18 patients with high risk of injury to IAN based on Rood's Criteria in an intra oral periapical radiographic examination, between the age group of 18 to 40 years, were included in the study. Preoperatively the impacted third molars were evaluated clinically as well as radiographically. Pederson Difficulty Index and Winter's Classification of impacted tooth was recorded. Coronectomy was done at the cemento enamel junction leaving the roots 2-3mm below the alveolar crest and primary closure was done. Patients were evaluated periodically for two years at six months interval. Post operative pain, swelling, IAN injury or any other complications were observed and recorded. RESULTS: None of the patients had IAN injury and none required second surgical removal. There was no incidence of post-operative infection and none required second surgical intervention. However, two of our patients had failed coronectomy (10%) due to mobilization of roots intra operatively and the roots were removed. One patient developed profuse bleeding intra-operatively in the failed coronectomy case. One patient had temporary lingual nerve paresthesia. CONCLUSION: Coronectomy procedure is effective in controlling inferior alveolar nerve injury following third molar surgery, in radiographically evaluated high risk cases and it has very low incidence of complications. PMID- 27656567 TI - Interlinking Periodontitis and Type 2 Diabetes Mellitus by Assessment of Crevicular Visfatin Levels in Health and in Disease Before and After Initial Periodontal Therapy. AB - INTRODUCTION: Visfatin is a new adipocytokine associated with both chronic periodontitis and type 2 diabetes mellitus independently. AIM: We aimed to estimate and compare the changes in the levels of visfatin in the Gingival Crevicular Fluid (GCF) of healthy subjects and in subjects with periodontitis with or without controlled Type 2 Diabetes Mellitus (T2DM) after administration of non-surgical periodontal therapy. MATERIALS AND METHODS: Forty two subjects were equally divided into Group 1 (healthy), Group 2 (systemically healthy with chronic periodontitis), Group 3 (subjects with chronic periodontitis having controlled T2DM). Defined clinical parameters were recorded at baseline and at one month follow-up period. Visfatin was assessed using enzyme linked immunosorbent assay. One way ANOVA and Tukey's multiple post hoc procedures were used. Pearson's correlation coefficient was used for correlation. RESULTS: Significant increase in the visfatin levels was seen with the highest values observed in diabetes with periodontal disease. Visfatin responded to non-surgical periodontal therapy as observed by significant decrease in levels after one month but even at this period diabetics showed the highest levels. CONCLUSION: Visfatin levels are highest in individuals with both periodontal disease and diabetes even after periodontal therapy. Individuals with T2DM may be at higher risk of developing periodontal disease. PMID- 27656568 TI - Comparative Evaluation of Flexural Strength of Provisional Crown and Bridge Materials-An Invitro Study. AB - INTRODUCTION: Provisional restorations serve a key role as a functional and esthetic try-in for the design of the final prosthesis. During selection of materials for this restoration, clinicians must consider physical properties, ease of handling, cost and patient satisfaction and approval. AIM: To evaluate and compare the flexural strength of provisional crown and bridge materials available commercially. MATERIALS AND METHODS: This in-vitro study was done to compare the flexural strength of six temporary crown and bridge materials available commercially at 24 hours, 8 days and after repair. Three poly methyl methacrylate based materials (DPI, SC10 and Trulon) and three bis-acrylic based composite resins (Protemp, Cooltemp and Luxatemp) were selected. A total of 72 specimens of dimensions 64mm*10mm*2.5mm were prepared from these materials (12 from each material) and divided into two groups (n=36). Specimens were stored in artificial saliva and were fractured after 24 hours and 8 days using Universal Testing Machine. The fractured samples from the 8 days study were then subjected to repair. A uniform space of 2mm and a 450 bevel was maintained for all the repaired samples for better distribution of forces. Flexural strength of these repaired samples was recorded using the same machine. RESULTs were recorded and statistically analysed by one-way Anova and Post hoc tests. RESULT: RESULTs revealed that there was decrease in flexural strength for all the materials tested from 24 hours to 8 days, though flexural strength between poly methyl methacrylate and bis-acrylic resins was similar at 24 hours and 8 days time interval. A substantial decrease was noticed in the strength of bis-acrylic composite resins after repair. CONCLUSION: From the current study it can be suggested that though there is decrease in flexural strength for all the materials from 24 hours to 8 days, both can be used to fabricate the provisional restorations. However, in the event of a fracture of a bis-acrylic provisional restoration, it may be more advantageous to make a new provisional restoration than to repair the fractured one. PMID- 27656569 TI - Prevalence of Carcinomatous Foci in Oral Leukoplakia: A Clinicopathologic Study of 546 Indian Samples. AB - INTRODUCTION: Oral Leukoplakia (OL), the most common potentially malignant disorder, is diagnosed clinically on the basis of exclusion of other lesions. In a country like India, where prevalence of oral cancer is very high, the issue of carcinomatous foci within OL at the time of initial diagnosis of leukoplakia has never been addressed before. AIM: To estimate the prevalence and risk factors for epithelial dysplasia as well as carcinoma within OL lesions at the time of initial clinical presentation in an Indian population with high prevalence of tobacco use. MATERIALS AND METHODS: Clinical and pathologic data (age, sex, lesion location and histopathologic grading) of 546 cases of leukoplakia were analyzed. The prevalence rate of dysplasia and carcinoma in 546 oral leukoplakia cases was calculated. Univariate analysis was performed to examine risk factors associated with the presence of carcinoma and dysplasia within the lesions. RESULTS: The male to female ratio in this study was 2:1. Majority of the patients irrespective of sex had a history of tobacco use. Of the total 85% of non homogeneous lesions and 70% for the homogeneous lesions were illustrating, features of epithelial dysplasia. The prevalence rate of carcinoma was 11.9%. In univariate analysis it was found that lesion site, clinical appearance, tobacco use were strongly correlated with the presence of carcinoma within OL. CONCLUSION: Our results demonstrate that majority of leukoplakia irrespective of its clinical appearance contain a dysplastic component and significant proportion contains carcinomatous foci. Lesions with certain features are more prone to have carcinomatous foci. However there is always a chance of finding foci of carcinoma in OL anywhere in the oral cavity. Therefore, excision biopsy is always mandatory before long term follow-up and treatment is planned. PMID- 27656570 TI - Ethical Conventions: A Study on Dental Practitioner's Knowledge and Practice of Ethics in their Line of Work in Bangalore, India. AB - INTRODUCTION: Dentistry, being one of the healing professions, has an obligation to society that its members will stick on to high ethical standards of conduct. In India, studies done to assess whether the dental practitioners adhere to ethics in their line of work are very meager. AIM: The present study was conducted to assess the knowledge and practice of ethics in their line of work among practicing dentists from various dental colleges in Bangalore, India. MATERIALS AND METHODS: A descriptive cross-sectional survey was conducted among 258 practicing dentists attached to various dental colleges in Bangalore city of Karnataka, India. Independent sample t-test was used to compare the knowledge and practice scores according to gender and qualification. One way ANOVA was used to compare knowledge and practice score according to practice type and practice period. RESULTS: Mean knowledge score among males is 8.9 as compared to 9.43 among females and mean practice scores among males was 8.25 as compared to 8.29 in females. Statistically significant differences were found in the mean knowledge and practice scores among graduate dentists and specialists. Mean knowledge score among graduate dentists was 8.44 as compared to 9.36 among specialists and mean practice scores among graduate dentists was 7.7 as compared to 8.53 in specialists. CONCLUSION: A significant association between the knowledge and practice scores was observed, implying that with an increase in knowledge, there was also an increase in the practices of ethics among study population. PMID- 27656572 TI - Sextant of Sapphires for Molar Distalization. AB - INTRODUCTION: Space analysis quantifies the amount of crowding within the arches estimating the severity of space discrepancy. The space gaining procedures include extraction and non-extraction procedures like expansion, proximal stripping and molar distalization. AIM: To identify features seen in molar distalization cases. MATERIALS AND METHODS: The sample size comprised 20 patients in whom molar distalization was decided as the treatment plan. The study models and lateral cephalograms of all the patients were taken. Occlusograms were obtained. Model analysis and cephalometric analysis were performed. Descriptive statistical analysis like mean, standard deviation, standard error and mode were done. RESULTS: The parameters in Question gave following results. The Bolton analysis showed anterior mandibular excess with mean value of 1.56mm+/-1.07. The first order discrepancy between maxillary central and lateral incisors was 5+/ 1.95. The premolar rotation showed mean value of 16.58+/-5.12. The molar rotation showed the value of 7.66+/-2.26. The nasolabial angle showed the mean of 101.25+/ 8.7 IMPA of 101.4+/-5.74. CONCLUSION: The six features studied in molar distalization cases [First order discrepancy between upper central and lateral incisors; Rotation of premolars and molars; Bolton's discrepancy in anterior dentition; Average to horizontal growth pattern; Proclined lower incisors and Obtuse nasolabial angle] can be taken as patterns seen in molar distalization cases and considered as a valid treatment plan. PMID- 27656571 TI - A Comparative Evaluation on Antimicrobial Effect of Honey, Neem Leaf Extract and Sodium Hypochlorite as Intracanal Irrigant: An Ex-Vivo Study. AB - INTRODUCTION: The major determinant of the success of root canal treatment depends on meticulous disinfection of the root canal using intracanal irrigants. The most commonly used root canal irrigant is sodium hypochlorite which has disadvantages of cytotoxicity and unpleasant taste. So there is a need to identify a more biocompatible root canal irrigant. AIM: The aim of this ex-vivo study was to evaluate the efficacy of 40% honey, 100% neem leaf extract and 5.25% sodium hypochlorite as an intracanal irrigant against the isolated microorganisms from infected root canal. MATERIALS AND METHODS: The samples were collected from infected root canals of 60 primary molar teeth indicated for pulpectomy. Alpha hemolytic Streptococci, gram negative bacilli, Candida, Staphylococci, Lactobacilli, Enterococci, Spore bearing gram positive bacilli and Micrococci were the microorganisms isolated from the samples. The zone of inhibition against the microbial growth was measured by agar well diffusion method. Statistical analysis was done by Repeated Analysis of Variance (ANOVA) and Bonferroni method. RESULTS: Statistical analysis showed that the means of the zones of inhibition measured in this study were 18.56mm, 2.09mm and 1.62mm for sodium hypochlorite, 100% neem leaf extract and 40% honey respectively. The significance was greater between sodium hypochlorite and the other two agents as p-value was <0.001. CONCLUSION: The results indicated that 5.25% sodium hypochlorite is more effective as root canal irrigant when compared with 100% neem leaf extract and 40% honey. It was also observed that 100% neem leaf extract has greater antimicrobial effect than 40% honey. PMID- 27656573 TI - Effect of Training School Teachers on Oral Hygiene Status of 8-10 Years Old Government School Children of Udaipur City, India. AB - INTRODUCTION: Provision of oral health knowledge to the children by their teachers at the school level can prove to be more fruitful because it is the time period during which the children begin to learn the basic oral hygiene practices and are most prone to dental caries. AIM: This study was carried out to assess the effect of training school teachers on oral hygiene status of 8-10 years old government school children of Udaipur city, India. MATERIALS AND METHODS: A total of nine school teachers and 279, 8-10 year old school children from two government schools were included in the study. The questionnaire on oral health knowledge and practice contained 17 questions to evaluate the knowledge and practice of children towards oral hygiene before and after the teachers training program. Baseline and six months post training data on oral health knowledge and practice was obtained by the questionnaire method. Baseline and six months post training data on oral hygiene status was obtained by OHI-S Index. Statistical analysis was done using software SPSS 22, the test used were McNemar's test, paired t-test. RESULTS: Pre and post training data were compared and it was found that there was a significant improvement in oral health knowledge and practices of school teachers and children. Also oral hygiene status of school children was significantly improved after the program. CONCLUSION: Results of the present study suggest that experiential learning is an effective school based oral health education method for improvement of oral hygiene in primary school children. PMID- 27656575 TI - Extra-nodal Diffuse Large B-cell Lymphoma (Germinal Center Type) Manifesting as Non-healing Extraction Socket. AB - Lymphomas occurring in the oral cavity are rare. They account only for about 2% of extra-nodal sites. Most of the lymphomas occur in the lymph nodes and in the oral cavity, the most commonly affected region is the Waldeyer's ring. Its occurrence in the mandibular gingiva is rare. Here, we describe a case of Diffuse Large B-cell Lymphoma manifested as a non-healing extraction socket in the mandibular right posterior region in a 62-year-old male patient. PMID- 27656574 TI - A Rare Simultaneous Occurrence of Odontogenic Keratocyst and Unicystic Ameloblastoma in Mandible: A Case Report. AB - Odontogenic Keratocyst (OKC) and Ameloblastomas are slow growing benign odontogenic lesions that primarily occur in the molar region of the mandible. Clinically and radiographically both ameloblastoma, especially the Unicystic ameloblastoma and OKC are indistinguishable due to the similar location of occurrence and the age of patients. It is very rare for these lesions to arise simultaneously in a patient's jaw. The co-occurrence of Ameloblastomas with odontogenic cysts or other odontogenic lesions (histologically in a single lesion)have already been described as combined or hybrid lesions. There are very few reported cases in the English literature for simultaneous occurrence of Unicystic Ameloblastoma and OKC as completely distinct lesions. Here we present such a rare case of the simultaneous occurrence of OKC and ameloblastoma in the posterior region of the mandible of a 22-year-old male in close relation. PMID- 27656576 TI - Papilliferous Keratoameloblastoma of the Mandible - A Rare Case Report. AB - Ameloblastomas are common odontogenic tumours that are benign and locally aggressive. Histopathologically, the tumor exhibits significant diversity with common and rare variants. Here, we report an unusual variant of a common odontogenic tumour in the mandibular posterior region on the right side in a 44 year old male patient. This is the sixth case of Papilliferous Keratoameloblastoma (PKA) to be reported in the English literature till date. More case reports are vital to determine the clinical, radiological, histopathological and behavioural aspects of this extremely rare histological type of ameloblastoma. This tumour awaits re-inclusion as a distinct entity in the future classifications of the WHO Classification of head and neck tumours upon further case accrual. PMID- 27656577 TI - Alveolar Bone Housing- A Modified Wilkodontics Approach- A Case Report. AB - Accelerated orthodontic treatment is the need of the hour in current scenario as the conventional orthodontics is time taking. Corticotomy assisted orthodontics have been used for years to reduce the treatment duration by reducing the resistance provided by alveolar bone housing. This case report describes the orthodontic treatment combined with the modification in conventional wilkodontic technique in a patient to accelerate tooth movement and shorten the treatment time with an anterior open bite and flared and spaced upper and lower incisors. Firstly plaque control was achieved with supra and subgingival scaling. A modified approach using periodontal access flap followed by vertical bone cuts in the cortical bone from the crest of the alveolar bone margin to 2mm-3mm below the apices of all the anterior teeth extending from upper left canine to upper right canine were performed. These vertical cuts were joined by horizontal cuts apically and flap repositioned. An MBT 0.018 inch appliance was bonded. Orthodontic therapy proceeded with frequent activation of the appliances to retract the incisors every two weeks. The total treatment time was four and half months with active period of two months and no adverse effects were observed at the end of active treatment. The modified decortication technique reduced the treatment time to a considerable extent. The interdental spacing closed and optimum overjet and overbite was achieved. PMID- 27656578 TI - KCOT Occurring in Bilateral Maxillary Sinus in Non-Syndromic Patient. AB - Odontogenic Keratocyst (OKC) also termed as Keratocystic Odontogenic Tumour (KCOT) (WHO 2005) is a pathology with unique behavior because of which it is under much scrutiny and continued study. The pathology usually presents itself commonly in mandible and less commonly in maxilla. The occurrence of KCOT in maxillary sinus is reported as rare and multiple occurrences are mostly associated along with the presence of Nevoid Basal Cell Carcinoma (NBCC) syndrome. Here, we present a rare case of bilateral Maxillary OKC involving maxillary sinuses, without the presence of NBCC syndrome. An interesting feature of this case is the presence of left upper third molar in ectopic position in maxillary sinus and a vertically impacted right third molar suggesting an origin from the dental lamina. PMID- 27656579 TI - Smile Reconstruction for the Preschoolers Using GRASCE Appliance - Two Case Reports. AB - Preschoolers with early childhood caries or extensive dental trauma may suffer from abnormal social interaction with their peers. Dentists face great challenges in the aesthetic rehabilitation of these young children. As the parental desire towards aesthetics is gaining more importance there is need for an anterior aesthetic appliance which may be used to replace these lost teeth. These case reports highlight a specific design which can be used successfully in day to day clinical practice. PMID- 27656580 TI - An Innovative and Simple Technique of Hollow Maxillary Complete Denture Fabrication. AB - Prosthetic rehabilitation of severely atrophic ridges has always been an ordeal for the clinician due to decreased support, stability and retention. Because of severe resorption the restorative space between maxillary and mandibular residual ridges is increased. Rehabilitation in such cases may result in increased height and weight of the prosthesis further compromising its retention and stability. This in turn overloads the underlying hard and soft tissues exacerbating ridge resorption so, in order to break this vicious cycle, the weight of the prosthesis needs to be reduced which can be achieved by making hollow prosthesis. This article describes a novel technique of fabricating a hollow maxillary complete denture. PMID- 27656581 TI - Early Eruption of Maxillary Pre Molar with Turner's Hypoplasia in a 5-Year-Old Boy. AB - Early eruption of permanent maxillary premolar appears to be a unique finding, at such an early chronological age. Untimely eruption of permanent maxillary premolar is discussed in a 5-year-old male patient. On intra oral examination grossly carious primary maxillary first molar (tooth number 54,64) were reported. The erupting teeth presented with a hypomineralized cusp tip. Extraction following space maintainer in 64 region was given. Pediatric dentist should consider these kinds of rarities in eruption pattern while examining a pediatric patient. PMID- 27656582 TI - Non-Syndromic Familial Keratocystic Odontogenic Tumour: A Rare Case Report in Japanese Identical Twins. AB - Keratocystic Odontogenic Tumour (KCOT) is unicystic or multicystic intraosseous benign tumour of odontogenic origin that recurs due to locally destructive behaviour. KCOTs are usually the first manifestation of Nevoid Basal Cell Carcinoma Syndrome (NBCCS), an autosomal dominant disorder also known as Gorlin's syndrome and they are most frequently observed familial symptom regardless of patients' nationality. In addition, the recurrence rate and multiplicity of KCOTs is relatively high as compared to that of other sporadic carcinomas. KCOT has been considered as a non-hereditary lesion and its familial onset is an extremely rare event in non-NBCCS cases. Here, we describe previously unreported non syndromic multiple KCOT cases in identical twins in a Japanese family. The subjects were female Japanese identical twins who were 26 and 27 years old, respectively, at the time of diagnosis for KCOT. They had no major or minor features of NBCCS other than KCOT. Although there were lesions that were likely to be dentigerous cysts based on radiographic findings, one of them was KCOT. This case report highlights the importance of precise diagnosis, choice of surgical method and careful observation for multiplicity or familial onset in sporadic KCOT cases without NBCCS. PMID- 27656583 TI - Serratiopeptidase - A Cause for Spread of Infection. AB - Serratiopeptidase is a proteolytic enzyme that has been used for reducing inflammation, it has antiedemic, analgesic, fibrinolytic and caesinolytic properties. Serratiopeptidase is often used in oral surgery for its anti inflammatory purpose after impaction surgery, maxillofacial trauma and infections but its use should be limited in cases of abscess due to its fibrinolytic activity. Here, we report a case of a buccal space abscess which had spread into deeper muscular layers after serratiopeptidase administration in a 32-year-old male without any systemic condition. Patient presented with a painful swelling on the right mid region of the face since seven days. Serratiopeptidase was discontinued. After routine blood investigation and ultrasonography, incision and drainage was done and the patient recovered after seven days of treatment. PMID- 27656584 TI - Prosthetic Management of a Nasal Septal Defect using a Custom Made Unilateral Intranasal Stent: A Case Report. AB - Various etiologies including congenital malformations, infections, trauma, iatrogenic causes or complications of systemic diseases can result in perforation of the nasal septum. The common symptoms associated with such defects include difficulty in breathing, nasal twang in voice, rhinorrhea, etc. Obturation can be achieved by insertion of a unilateral nasal stent. An attempt has been made in the present report to address the prosthetic management of pateint having nasal septum perforation utilizing a unilateral, custom made heat cured acrylic stent and the details of the technique are presented. PMID- 27656585 TI - Prosthetic Rehabilitation of Lower Limb with RTV Siliconee Using Prosthodontic Clinical and Laboratory Techniques - A Case Report. AB - Amputation of all or part of a limb may be due to systemic disease, vascular disease, infection, local injury or trauma. Partially amputated lower limbs present a variety of unique clinical and prosthetic challenges, because of distinctly different amputation levels of the lower limb. A female patient with history of Partial Foot Amputation (PFA) surgery at metatarsophalangeal joint level, due to crush injury reported for prosthetic rehabilitation. This case was successfully rehabilitated using room temperature vulcanizing (RTV) medical grade silicone for fabrication of foot prosthesis. Though limited in its function, it amply proves that the clinical and laboratory techniques used in fabrication of maxillofacial prosthesis can be effectively adapted for the fabrication of body prosthesis like toes and feet to enhance the quality of life of the patients. The patient was reviewed every year for three years. PMID- 27656586 TI - Desmoplastic Ameloblastoma Arising in a Dentigerous Cyst - A Case Report and Discussion. AB - Dentigerous cyst is a fairly common odontogenic cyst with an uncomplicated prognosis. However, reports of odontogenic and non-odontogenic tumors arising from the cysts have been published for many years. Therefore, the importance of thorough histopathological examination and regular follow-up cannot be overemphasized. Here is a case report of a possible development of desmoplastic ameloblastoma from a dentigerous cyst. This case is unique for two main reasons. Firstly, to our knowledge such a case has not been reported previously. Secondly, the tumor seemed to arise from the capsule and not from lining of the dentigerous cyst. Transformation of odontogenic rests into cysts is known to occur in the syndromic cases of odontogenic keratocysts (resulting in recurrent and daughter cysts) but not in dentigerous cysts. This case report may prompt greater interest in the role of the supposedly inactive odontogenic nests in the capsule of these cysts. PMID- 27656587 TI - Clinical Effectiveness of Aloe Vera in the Management of Oral Mucosal Diseases- A Systematic Review. AB - INTRODUCTION: Aloe vera is well known for its medicinal properties which lead to its application in treating various diseases. Its use in treating oral lesions has not been much documented in literature. AIM: Although, systematic reviews on aloe vera and its extracts have been done earlier, but in relation to oral diseases this is the first systematic review. The aim of the present systematic review was to compile evidence based studies on the effectiveness of Aloe vera in treatment of various oral diseases. MATERIALS AND METHODS: Computerized literature searches were performed to identify all published articles in the subject. The following databases were used: PUBMED [MEDLINE], SCOPUS, COCHRANE DATABASE, EMBASE and SCIENCE DIRECT using specific keywords. The search was limited to articles published in English or with an English Abstract. All articles (or abstracts if available as abstracts) were read in full. Data were extracted in a predefined fashion. Assessment was done using Jadad score. RESULTS: Fifteen studies satisfied the inclusion criteria. Population of sample study ranged from 20 patients to 110 patients with clinically diagnosed oral mucosal lesions. Out of 15 studies, five were on patients with oral lichen planus, two on patients with oral submucous fibrosis, other studies were carried on patients with burning mouth syndrome, radiation induced mucositis, candida associated denture stomatitis, xerostomic patients and four were on minor recurrent apthous stomatitis. Most studies showed statistically significant result demonstrating the effectiveness of Aloe vera in treatment of oral diseases. CONCLUSION: Although there are promising results but in future, more controlled clinical trials are required to prove the effectiveness of Aloe vera for management of oral diseases. PMID- 27656589 TI - Modified Interim Mandibular Advancement (MIMA) Appliance for Symptomatic Correction of Obstructive Sleep Apnea. AB - Obstructive Sleep Apnea (OSA) is a chronic, progressive, multifactorial, life threatening disorder that causes significant impact on patient's life. Patients with OSA [Apnea/Hypopnea Index (AHI)>30] who cannot tolerate Continuous Positive Airway Pressure (CPAP) therapy or are not surgical candidates may benefit from oral appliances. This paper describes interim appliance devised from existing Hawley's retainer in patients with OSA. A 38-year-old man of athletic built with history of orthodontic treatment six months back due to esthetic concerns and wearing upper Hawley's retainer, reported with chief complaint of frequent nocturnal awakening along with excessive daytime somnolence. Based on diagnostic aids, he was diagnosed with Class II Division 1 malocclusion with severe mandibular retrusion. Sleep test revealed AHI score of 34, suggestive of severe OSA. With ENT and Oral surgeon concurrence, mandibular advancement of 7mm with Bilateral Sagital Split Osteotomy (BSSO) with distraction was contemplated as a viable functional and curative stable treatment plan. Because of non-adherence and non-compliance with CPAP therapy and on request of patient, an interim anterior positioning appliance was devised to facilitate comfortable sound sleep till the time surgery is impending. After three months of wearing this customized appliance, improved quality of sleep was discernible; both subjectively as reported by patient and objectively using sleep test (AHI=9.8). PMID- 27656588 TI - Apical Periodontitis - Is It Accountable for Cardiovascular Diseases? AB - The aim of this review was to assess the relationship between apical periodontitis and cardiovascular diseases and the predictive factors regarding this association. Cross sectional and observational studies have been included, which are mostly retrospective. A comprehensive search was performed in the Systematic Electronic Databases, PUBMED and MEDLINE from 1919 till September 2014. Articles were also hand searched. From 86 studies identified, all were read and 58 articles which were relevant were included in the text. Some articles were excluded because they were pertaining to periodontology and other systemic disorders. Some were solely animal studies and were thus excluded. Our results suggest an independent association between cardiovascular diseases and apical periodontitis. A causal relationship could not be established since weak parameters of risk have been assessed in the studies, population taken is difficult to compare and other confounding factors have not been ruled out. Only a more focused and better instituted scientific research can determine this association. Establishing a cause and effect relationship between apical periodontitis and cardiovascular diseases can affect the course of treatment of cardiovascular diseases. It is not only of interest from the scientific point of view but also from public health perspective. PMID- 27656590 TI - Replication of Palatal Rugae and Incorporation in Complete Denture. PMID- 27656591 TI - Central Giant Cell Granuloma of Jaw with Multiple, Multifocal Recurrences. PMID- 27656592 TI - Interdisciplinary Management of Impacted Supernumerary Tooth between Roots of Permanent Teeth-A Management Dilemma? PMID- 27656593 TI - Cast Partial Denture with Cekapreci-Sagix Extra Coronal Attachment and Obturator for Rehabilitation of Patient with Maxillary Defect. PMID- 27656594 TI - Minor Salivary Gland Carcinoma of Hard Palate with CT Findings- Report of a Case. PMID- 27656595 TI - Endodontic Management of Mandibular First Molar with Six Canals Using CBCT- Report of a Case. PMID- 27656596 TI - Palato-Radicular Groove: A Rare Entity in Maxillary Central Incisor Leading To Endo-Perio Lesion. PMID- 27656597 TI - Prosthetic Rehabilitation of Squamous Cell Carcinoma of Orbit: A Clinical Report. PMID- 27656598 TI - Letter to the Editor on "Clinical Evaluation of Success of Primary Teeth Pulpotomy Using Mineral Trioxide Aggregate, Laser and Biodentine - An Invivo Study". PMID- 27656599 TI - Moulding Faces at an Early Age-A Case Series. AB - Certain malocclusions have to be treated at an early age to avoid surgeries for the correction in the future. Introduction of functional appliances has reduced the elimination and correction of skeletal as well as dental discrepancies. Proper case selection taking into consideration skeletal and dental age with the use of various diagnostic aids helps us to identify and treat the malocclusions before it is too late. In this case series, we report three patients with skeletal jaw malrelationship treated with functional and orthopaedic appliances. PMID- 27656600 TI - Inflammation and endothelium response in epileptic patients: A case-control study. AB - BACKGROUND: Blood brain barrier (BBB) permeability plays an important role in the brain impairments. The barrier is composed of endothelium cells, due to the presence of tight junctions that connect endothelium cells. The failure of BBB function has triggering chronic or acute seizures through brain inflammation and BBB permeability. Seizure induces vasodilation, BBB leakage and up-regulation of vascular cell adhesion molecules which able to bind integrins blood leukocytes. MATERIALS AND METHODS: In this case-control study we included 40 epileptic patients who were sampled during a seizure as a case group and 20 healthy subjects as a healthy control group. Plasma levels of the inflammation and endothelium markers including intercellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), interleukin 1 beta (IL-1beta) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assays (ELISAs). RESULTS: The ICAM and VCAM concentration in the epileptic patients (135.8 +/- 5.35) (52.04 +/- 4.24) were significantly higher than healthy control group (110.32 +/- 5.04) (23.38 +/- 3.01) (P < 0.005). IL-1 beta concentration was not significantly different between groups (P = 0.594). However, CRP level was significantly up regulated in epileptic patients (P < 0.005). CONCLUSION: Epileptic patients have BBB leakage and dysfunction as the up-regulation of the endothelium cytokines showed. The BBB leakage may be the result of the inflammatory impairment. PMID- 27656601 TI - Identification of Candida species in patients with oral lesion undergoing chemotherapy along with minimum inhibitory concentration to fluconazole. AB - BACKGROUND: Various species of Candida, especially Candida albicans was known as the most important etiological agent of fungal infections. Oral candidiasis is the most common fungal infection in patients undergoing chemotherapy. The purpose of this study was to identify Candida species from oral lesions of these patients and antifungal susceptibility of the clinical isolates. MATERIALS AND METHODS: Among 385 patients with cancer, 55 (14.3%) showed oral lesions. Oral swabs were performed to identify the yeasts using direct smear and CHROMagar medium. Micro dilution method was prepared in different concentrations of fluconazole and minimum inhibitory concentration and minimum fungicidal concentration of each species were compared. RESULTS: Oral candidiasis confirmed in 36 cases by direct examination and culture. C. albicans and non-albicans represented in 26 (72.2%) and 10 (27.8%) of the isolates, respectively. 76.5% of C. albicans and 23.5% non albicans isolates were resistant to fluconazole. Data were shown that 62% and 30.7% of resistant strains of C. albicans were found in patient with gastrointestinal cancer and lymphoma respectively. CONCLUSION: Data were shown that C. albicans is the most commonly identified species in oral candidiasis and majority of fluconazole resistant C. albicans were found in patients with gastrointestinal cancer and lymphoma. Therefore, we recommend an alternative drug instead of fluconazole as a first line of treatment for these type of cancers and administration of fluconazole in patients undergoing chemotherapy should be prescribed in accordance with the type of cancer. PMID- 27656603 TI - Obesity phenotypes and resorption percentage after breast autologous fat grafting: Rule of low-grade inflammation. AB - BACKGROUND: One of the main reasons why the breast fat grafting was questioned is that there may be lipofilling resorption. In the literature, the resorption rate reported over the 1(st) year is highly variable (20-90%). OBJECTIVE: The aim of this work was to identify the biochemical and clinical parameters, which increase fat graft maintenance in breast reconstruction. MATERIALS AND METHODS: A sample of 19 patients was treated with fat grafting mixed with platelet-rich plasma. A complete screening of anthropometry, body composition, and blood biochemical parameters was assessed using the standardized equipment. Pre- and post-operative evaluation was performed, which included a complete clinical examination, photographic assessment, nuclear magnetic resonance imaging of the soft tissue, and ultrasound. The follow-up period was 2 years. RESULTS: The authors divided the results into two types of patients: "responder" and "not a responder." In the "responder" group patients with normal weight, gynoid fat distribution, obese, with normal blood biochemical parameters, and atherogenic indices but with high preoperative values of platelet-to-lymphocyte ratio (PLR) (174.49) and neutrophil lymphocyte ratio (NLR) (2.65) showed a greater increase of fat graft maintenance at 6 and 12 months after the last lipofilling session. In the "not responder group" patients with overweight, android fat distribution, obese, high values of atherogenic indices, but with normal preoperative NLR and PLR ratios showed a lower fat graft maintenance at 6 and 12 months. CONCLUSION: We assume, the problem of fat resorption may be resolved by analysis of body composition and by examine the predictive role of preoperative markers of low-grade inflammation. PMID- 27656602 TI - Genistein potentiates the effect of 17-beta estradiol on human hepatocellular carcinoma cell line. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This cancer may be due to a multistep process with an accumulation of epigenetic alterations in tumor suppressor genes (TSGs), leading to hypermethylation of the genes. Hypermethylation of TSGs is associated with silencing and inactivation of them. It is well-known that DNA hypomethylation is the initial epigenetic abnormality recognized in human tumors. Estrogen receptor alpha (ERalpha) is one of the TSGs which modulates gene transcription and its hypermethylation is because of overactivity of DNA methyltransferases. Fortunately, epigenetic changes especially hypermethylation can be reversed by pharmacological compounds such as genistein (GE) and 17-beta estradiol (E2) which involve in preventing the development of certain cancers by maintaining a protective DNA methylation. The aim of the present study was to analyze the effects of GE on ERalpha and DNMT1 genes expression and also apoptotic and antiproliferative effects of GE and E2 on HCC. MATERIALS AND METHODS: Cells were treated with various concentrations of GE and E2 and the 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used. Furthermore, cells were treated with single dose of GE and E2 (25 MUM) and flow cytometry assay was performed. The expression level of the genes was determined by quantitative real time reverse transcription polymerase chain reaction. RESULTS: GE increased ERalpha and decreased DNMT1 genes expression, GE and E2 inhibited cell viability and induced apoptosis significantly. CONCLUSION: GE can epigenetically increase ERalpha expression by inhibition of DNMT1 expression which in turn increases apoptotic effect of E2. Furthermore, a combination of GE and E2 can induce apoptosis more significantly. PMID- 27656604 TI - Congenital nasal pyriform aperture stenosis: A case with accompanying short lingual frenulum. AB - Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of nasal obstruction. We presented a case of CNPAS with accompanying short lingual frenulum. Surgical dilatation without osteotomy was used, and the infant had normal growth and development. In these cases, the less invasive surgical methods can be effective. PMID- 27656605 TI - Determination of antifungal susceptibility patterns among the environmental isolates of Aspergillus fumigatus in Iran. AB - BACKGROUND: In recent years, triazole-resistant environmental isolates of Aspergillus fumigatus have emerged in Europe and Asia. Azole resistance has been reported in patients who are treated with long-term azole therapy or exposure of the fungus spores to the azole fungicides used in agriculture. To date, a wide range of mutations in A. fumigatus have been described conferring azole resistance, which commonly involves modifications in the cyp51A gene. We investigated antifungal susceptibility pattern of environmental isolates of A. fumigatus. MATERIALS AND METHODS: In this study, 170 environmental samples collected from indoors surfaces of three hospitals in Iran. It was used beta tubulin gene to confirm the all of A. fumigatus isolates, which was identified by conventional methods. Furthermore, the antifungal susceptibility of itraconazole, voriconazole, and posaconazole was investigated using broth microdilution test, according to European Committee on Antimicrobial Susceptibility testing reference method. RESULTS: From a total of 158 environmental molds fungi obtained from the hospitals, 58 isolates were identified as A. fumigatus by amplification of expected size of beta-tubulin gene (~500 bp). In this study, in vitro antifungal susceptibility testing has shown that there were not high minimum inhibitory concentration values of triazole antifungals in all of the 58 environmental isolates of A. fumigatus. CONCLUSION: Our findings demonstrated that there was not azole-resistant among environmental isolates of A. fumigatus. Medical triazoles compounds have structural similarity with triazole fungicide compounds in agriculture, therefore, resistance development through exposure to triazole fungicide compounds in the environment is important but it sounds there is not a serious health problem in drug resistance in environmental isolates in Iran. PMID- 27656606 TI - Comparing three clinical prediction rules for primarily predicting the 30-day mortality of patients with pulmonary embolism: The "Simplified Revised Geneva Score," the "Original PESI," and the "Simplified PESI". AB - BACKGROUND: Patients with suspected pulmonary embolism (PE) should be evaluated for the clinical probability of PE using an applicable risk score. The Geneva prognostic score, the PE Severity Index (PESI), and its simplified version (sPESI) are well-known clinical prognostic scores for PE. The purpose of this study was to analyze these clinical scores as prognostic tools. MATERIALS AND METHODS: A historical cohort study was conducted on patients with acute PE in Al Zahra Teaching Hospital, Isfahan, Iran, from June 2013 to August 2014. To compare survival in the 1-month follow-up and factor-analyze mortality from the survival graph, Kaplan-Meier, and log-rank logistic regression were applied. RESULTS: Two hundred and twenty four patients were assigned to two "low risk" and "high risk" groups using the three versions of "Simplified PESI, Original PESI, and Simplified Geneva." They were followed for a period of 1 month after admission. The overall mortality rate within 1 month from diagnosis was about 24% (95% confidence interval, 21.4-27.2). The mortality rate of low risk PE patients was about 4% in the PESI, 17% in the Geneva, and <1% in the simplified PESI scales (P < 0.005). The mortality rate among high risk patients was 33%, 33.5%, and 27.5%, respectively. CONCLUSIONS: Among patients with acute PE, the simplified PESI model was able to accurately predict mortality rate for low risk patients. Among high risk patients, however, the difference between the three models in predicting prognosis was not significant. PMID- 27656607 TI - Comparative study of shock wave therapy and Laser therapy effect in elimination of symptoms among patients with myofascial pain syndrome in upper trapezius. AB - BACKGROUND: The aim of this study is to compare the effects of laser therapy and shock wave therapy for symptoms treatment among patients with MPS in the upper trapezius muscle. MATERIALS AND METHODS: In a clinical trial study, 46 patients were selected based on the clinical criteria and physiathrist diagnosis. Subjects were randomized into two groups as follows: Twenty individuals were assigned to exercise-medication-laser therapy group, and 26 to exercise-medication-shock wave therapy group. The pain was assessed based on visual analog scale (VAS), neck disability index (NDI), and SPADI in three stages: Before treatment, subsequently after treatment, and a month after treatment. RESULTS: One man and 19 women, age group of 45.3 +/- 7.7 years, were assigned into laser therapy group. Two men and 24 women, average age group of 42.3 +/- 10.4 were assigned into shock wave therapy group. A significant difference was found among our study groups before treatment and after starting treatment for VAS, NDI, and SPDI indices, that is, two methods of treatments were effective (P < 0.001). However, among these two treatment methods, laser therapy provided higher effect on VAS and NDI as compared to the radial shock wave method (P < 0.05) in 2 weeks from starting the treatment (consequent to treatment). CONCLUSION: According to this study results, we can conclude that shock wave and laser therapy results on similar effect in long-term for relieve of pain and eliminating symptoms in patients with myofascial but laser provides a faster optimal results. PMID- 27656608 TI - Cytotoxic, antioxidant and phytochemical analysis of Gracilaria species from Persian Gulf. AB - BACKGROUND: Marine algae, also called seaweeds, are abundantly present in the coastal area of Iran, especially in Persian Gulf. These plants contain important phytochemical constituents and have potential biological activities. The present study investigated the presence of phytochemical constituents and total phenolic quantification of the seaweeds Gracilaria salicornia and Gracilaria corticata. Cytotoxicity of seaweeds was tested against HT-29, HeLa, and MCF-7 cell lines. Antioxidant potential of these two Gracilaria species was also analyzed. MATERIALS AND METHODS: Extracts of G. salicornia and G. corticata were subjected to phytochemical and cytotoxicity tests. Phytochemical screenings were employed to identify the chemical constituents and total phenolic content. Cytotoxicity was characterized by IC50 of human cancer cell lines (MCF-7, HeLa, and HT-29) using sulforhodamine assay. Antioxidant activities were evaluated using 2,2 diphenyl-1-picrylhydrazyl. RESULTS: The analysis revealed that tannins were the most abundant compounds in G. corticata while sterols and triterpenes were the most abundant ones in G. salicornia, but the total phenolic content of the two seaweeds was similar. Cytotoxic results showed that both species could inhibit cell growth effectively, especially against HT-29 cell line. CONCLUSION: Considerable phytochemicals, high antioxidant potential, and moderate cytotoxic activity of G. salicornia and G. corticata make them appropriate candidates for further studies and identification of their bioactive principles. PMID- 27656610 TI - The effect of extremely low-frequency magnetic field (50-60 Hz) exposure on spontaneous apoptosis: The results of a meta-analysis. AB - BACKGROUND: This paper is a meta-analysis of the published data from in vitro studies to evaluate whether spontaneous apoptosis might be influenced by extremely low frequency (ELF) magnetic fields (MFs). MATERIALS AND METHODS: A comprehensive scientific literature search in electronic databases was conducted and studies covering the period 2000-2010 were selected. Then, published studies involving the desired topic were retrieved. The inclusion criteria were percentage of apoptosis in the cells exposed to 50-60 Hz ELF-MFs. The statistical analysis was performed by comprehensive meta-analysis version 2. RESULTS: The summary measure of association (95% confidence interval) for all 18 effect estimated from 8 studies was 1.18 (1.15, 1.20). Heterogeneity among studies was found. There was no evidence of publication bias for the association between exposure to MF and apoptosis risk. CONCLUSION: Our meta-analysis provided conclusive data that ELF-MFs can increase apoptosis in cancer and normal cells. Furthermore, there is a possibly individual intensity and time range with maximum created effect according to window effect. PMID- 27656609 TI - Beneficial effects of L-arginine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced neuronal degeneration in substantia nigra of Balb/c mice. AB - BACKGROUND: L-arginine has been recently investigated and proposed to reduce neurological damage after various experimental models of neuronal cellular damage. In this study, we aim to evaluate the beneficial effects of L-arginine administration on the numerical density of dark neurons (DNs) in the substantia nigra pars compacta (SNc) of Balb/c mice subjected to 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) administration. MATERIALS AND METHODS: Male Balb/c mice were randomly divided into 4 groups (n = 7 each): MPTP only; saline only (control); MPTP + L-arginine; and L-arginine only. The animals were infused intranasally with a single intranasal administration of the proneurotoxin MPTP (1 mg/nostril). L-arginine (300 mg/kg) was administrated intraperitoneally once daily for 1-week starting from 3 days after MPTP administration. Cavalieri principle method was used to estimate the numerical density of DNs in the SNc of different studied groups. RESULTS: Twenty days following MPTP administration, the number of DNs was significantly increased when compared to sham-control and L arginine-control groups (P < 0.05). Nevertheless, our results showed that L arginine administration significantly decreased the numerical density of DNs in SNc of mice. CONCLUSION: This investigation provides new insights in experimental models of Parkinson's disease, indicating that L-arginine represents a potential treatment agent for dopaminergic neuron degeneration in SNc observed in Parkinson's disease patients. PMID- 27656611 TI - Effect of maternal diabetes on gliogensis in neonatal rat hippocampus. AB - BACKGROUND: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). MATERIALS AND METHODS: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. RESULTS: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P < 0.05). We also found an insignificant up-regulation in the expression of GFAP and the mean number of positive cells in the insulin-treated diabetic group neonates as compared to control group (P > 0.05). CONCLUSION: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus. PMID- 27656612 TI - Occurrence of airborne vancomycin- and gentamicin-resistant bacteria in various hospital wards in Isfahan, Iran. AB - BACKGROUND: Airborne transmission of pathogenic resistant bacteria is well recognized as an important route for the acquisition of a wide range of nosocomial infections in hospitals. The aim of this study was to determine the prevalence of airborne vancomycin and gentamicin (VM and GM) resistant bacteria in different wards of four educational hospitals. MATERIALS AND METHODS: A total of 64 air samples were collected from operating theater (OT), Intensive Care Unit (ICU), surgery ward, and internal medicine ward of four educational hospitals in Isfahan, Iran. Airborne culturable bacteria were collected using all glass impingers. Samples were analyzed for the detection of VM- and GM-resistant bacteria. RESULTS: The average level of bacteria ranged from 99 to 1079 CFU/m(3). The highest level of airborne bacteria was observed in hospital 4 (628 CFU/m(3)) and the highest average concentration of GM- and VM-resistant airborne bacteria were found in hospital 3 (22 CFU/m(3)). The mean concentration of airborne bacteria was the lowest in OT wards and GM- and VM-resistant airborne bacteria were not detected in this ward of hospitals. The highest prevalence of antibiotic resistant airborne bacteria was observed in ICU ward. There was a statistically significant difference for the prevalence of VM-resistant bacteria between hospital wards (P = 0.012). CONCLUSION: Our finding showed that the relatively high prevalence of VM- and GM-resistant airborne bacteria in ICUs could be a great concern from the point of view of patients' health. These results confirm the necessity of application of effective control measures which significantly decrease the exposure of high-risk patients to potentially airborne nosocomial infections. PMID- 27656613 TI - Nasal carriage screening of community-associated methicillin resistant Staphylococcus aureus in healthy children of a developing country. AB - BACKGROUND: The rapid emergence and spread of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has raised considerable public health concern in both developed and developing countries. The current study aimed to address the extent of this phenomenon in healthy preschool children of a developing country. MATERIALS AND METHODS: We conducted a prospective study from April 2013 to March 2014 on 410 healthy 2-6 years old preschool children in Isfahan, Iran. Demographic medical data and nasal samples were collected from the participating children. Isolates were identified as S. aureus and MRSA based on microbiological and molecular tests, including the presence of eap and mecA genes. RESULTS: The overall prevalence of S. aureus and CA-MRSA nasal carriage was 28% (115/410) and 6.1% (25/410), respectively. The identity of isolates was confirmed by molecular assay. The factors that were independently associated with nasal carriage of S. aureus were: Children crowding in day-care nurseries and income level of families. A total of 20/90 (22.2%) of methicillin-susceptible S. aureus and all 25 CA-MRSA displayed multiple drug resistance to 3-8 antibiotics. CONCLUSIONS: The current report reflects issues and concerns that the high rate of colonization by CA-MRSA in Iranian healthy children provides obliging evidence that MRSA have established a foothold in the community and are emerging as important health threatening pathogens. It is suggested that we need more effective infection control measures to prevent transmission of nasal CA-MRSA in healthy preschool children. PMID- 27656614 TI - The effect of hydroxychloroquine on glucose control and insulin resistance in the prediabetes condition. AB - BACKGROUND: Hydroxychloroquine can improve most underlying coronary risk factors; however, there are a few studies on the effects of hydroxychloroquine on blood glucose and insulin resistance. The current study aimed to assess the effects of hydroxychloroquine on blood glucose control status as well as on level of lipid profile and inflammatory biomarkers in prediabetic patients. MATERIALS AND METHODS: In a randomized, double-blinded, controlled trial, 39 consecutive patients who were suffering from prediabetes and were referred to the Isfahan Endocrinology Center in January 2013 were randomly assigned to receive hydroxychloroquine (6.5 mg/kg/day) (n = 20) or placebo (n = 19) for 12 weeks. The biomarker indices and anthropometric parameters were tested before and after completion of treatment. RESULTS: In both groups of patients receiving hydroxychloroquine and placebo, except for serum level of insulin that was significantly elevated after treatment by hydroxychloroquine, the changes in other parameters remained insignificant. Both groups experienced increase of insulin level, but this change was considerably higher in those groups receiving hydroxychloroquine. The group receiving hydroxychloroquine experienced reduction of glucose at 60 min of Oral Glucose Tolerance Test (OGTT) test after intervention, while the placebo group experienced increase of blood glucose at the same time. CONCLUSION: The use of hydroxychloroquine may increase the serum insulin level in patients with prediabetic states who are at risk of developing diabetes mellitus. PMID- 27656615 TI - Isolated pulmonary candidiasis in a patient with diabetes mellitus: A rare case report. AB - Fungal infections are as a cause of morbidity and mortality in immunocompromise patients. Because the respiratory tract is colonized with Candida, the presence of this agent in respiratory specimens makes the diagnosis of Candida pneumonia problematic. Candida pneumonia is a rare infection, and the majority of cases are secondary to hematogenous dissemination. Furthermore isolated Candida pneumonia originating from endotracheal inoculation is an extremely rare entity. We describe a case of isolated pulmonary candidiasis in the form multiple nodular lesions in a patient with long-term history of diabetes mellitus without evidence of fungemia or systemic involvement who responded to antifungal therapy. PMID- 27656616 TI - A survey on concomitant common bile duct stone and symptomatic gallstone and clinical values in Shiraz, Southern Iran. AB - BACKGROUND: Common bile duct stone (CBDS) as a result of gallstone is one of the gastrointestinal disorders. In this study, the incidence of CBDS and symptomatic gallstone in Shiraz were investigated, and their management suggested. MATERIALS AND METHODS: This is a retrospective study that enrolled among 560 patients. The incidence of gallstone together with CBDS was evaluated using an ultrasonography studyand clinical data in the period between March 2014 and 2014 in Shiraz. Comparison between data was done using Student's t-test or Chi-square test. RESULTS: Of these patients, 18.6% were male, and 81.4% were female with a mean age of 47.67 +/- 0.74 years. The concomitant rate of gallstone and CBDS was 8.6%. 6.8% of patients with concomitant of gallstone and CBDS showed symptoms while 1.8% had not been diagnosed before the operation. The mean of serum alkaline phosphatase level in patients with the only gallstone was 255.80 IU/L and patients with concomitant gallstone, and CBDS was 580.88 IU/L with a significant difference between two groups (P < 0.001). Furthermore, liver function tests (aspartate aminotransferase, alanine transaminase) showed a significant difference between two groups of patients (P < 0.01, P < 0.001). CONCLUSIONS: Clinical variables such as tenderness, fever, and Morphy sign were more severein patients with concomitant gallstone and CBDS. The concomitant rate of gallstone and CBDS in our society is less that Western countries and asymptomatic patients showed fewer ratios than other countries. We think the approach for asymptomatic CBDS patients with gallstone can be affected by our results. PMID- 27656617 TI - Variations in ESR and CRP in total knee arthroplasty and total hip arthroplasty in Iranian patients from 2009 to 2011. AB - BACKGROUND: Implantation of joint prosthesis, either in the knee or in the hip, may cause some problems such as an infection, so that a timely treatment is essential. In this respect, discovering a marker detecting the incidence of an infection is one of the requirements of arthroplasty. The present study was conducted to determine variations of two markers in arthroplasty and infection incidence in Iranian patients. MATERIALS AND METHODS: This prospective study was carried out in Isfahan's educational treatment centers from 2009 to 2011 on patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA) surgical operations. The erythrocyte sedimentation rate (ESR) was measured by Sed rate device (Lena) and C-reactive protein (CRP) by autoanalyzer device (Erba) with the unit of ng/dL. The patients underwent ESR and CRP tests the day before operation, the day of operation, and 1, 2, 5, and 15 days and 1, 3, 6, and 12 months after operation. RESULTS: Mean ESR increased during the first 5 days then decreased gradually lasting for 3 months. After 1 year it increased to a level higher than before the operation. The variations in ESR values were 19.1 +/ 12.9 before the operation and 21.14 +/- 10.8 after 1 year with significant difference (P < 0.001). The level of CRP had an upward trend from the first day after operation and reached its maximum on the second day, then had a downward trend up to 1 month after the operation; however, it did not reach its preoperative level during 1 year. CONCLUSION: ESR and CRP and their variations can be suitable factors to detect probable infections in patients undergoing TKA and THA operations. PMID- 27656618 TI - Effect of add-on valproate on craving in methamphetamine depended patients: A randomized trial. AB - BACKGROUND: Methamphetamine dependence lead to the compulsive use, loss of control, and social and occupational dysfunctions. This study aimed to compare the effect of valproate in reducing the craving in methamphetamine dependents. MATERIALS AND METHODS: This is a randomized, double-blind, controlled clinical trial on 40 men of 18-40 years old referred to Noor Hospital during December 2012 September 2013 in Isfahan, Iran. The subjects participated in matrix program and randomly were divided into two groups of valproate and placebo. A 4-months program of intervention with valproate or placebo was arranged for each group. The rate of craving to methamphetamine and positive methamphetamine urine tests were evaluated in both groups every 2 weeks using cocaine craving questionnaire brief (CCQ-Brief) and urine test. After the 4 months (active treatment with valproate and placebo), the drug was tapered and discontinued within 10 days, and patients were introduced to self-help groups and monitored regularly on a weekly basis over another 3 months. Collected data were analyzed with SPSS 20 using analysis of covariance repeated measure, Chi-square, and t-test. RESULTS: CCQ score of the intervention group was significantly less than the placebo group (P < 0.001), except on weeks 1, 3, and 28. The ratio of a positive urine test for methamphetamine in the intervention group was significantly lower than the control group in all screenings except weeks 3 and 28. CONCLUSION: Adding valproate to matrix program in the treatment of methamphetamine dependence showed significant effect on the reduction of the craving to methamphetamine. PMID- 27656619 TI - The science behind the Olympic glory. PMID- 27656620 TI - Size dependent classification of heat shock proteins: a mini-review. AB - Molecular chaperones are ubiquitous and abundant within cellular environments, functioning as a defense mechanism against outer environment. The range of molecular chaperones varies from 10 to over 100 kDa. Depending on the size, the specific locations and physiological roles of molecular chaperones vary within the cell. Multifunctionality of heat shock proteins (HSPs) expressed via various cyto-stress including heat shock have been spotlighted as a reliable prognostic target biomarker for therapeutic purpose in neuromuscular disease or cancer related studies. HSP also plays a critical role in the maintenance of proteins and cellular homeostasis in exercise-induced adaptation. Such various functions of HSPs give scientists insights into intracellular protective mechanisms in the living body thus HSPs can be target molecules to know the defense mechanism in cellular environment. Based on experimental results regarding small to large scaled HSPs, this review aims to provide updated important information regarding the modality of responses of intracellular HSPs towards extracellular stimulations. Further, the expressive mechanisms of HSPs data from tremendous in vivo and in vitro studies underlying the enhancement of the functionality of living body will be discussed. PMID- 27656621 TI - Matrix metalloproteinase and tissue inhibitor of metalloproteinase responses to muscle damage after eccentric exercise. AB - High-intensity eccentric exercise is known to induce muscle damage leading to inflammatory responses and extracellular matrix (ECM) degradation. These degradation processes involve enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). MMPs are calcium and zinc dependent proteolytic enzymes that play a role in ECM degradation and recruitment of inflammatory and myogenic cells into the damaged site. In contrast, TIMPs inhibit MMP-induced ECM degradation to maintain normal homeostasis in ECM. Recently, several studies have examined the process of muscle remodeling and the roles of ECM, MMPs, and TIMPs in exercise-induced muscle damage. However, the results of these studies are not inconsistent. In the present mini-review, we will discuss the responses of MMP and TIMP to eccentric exercise based on the literature review. PMID- 27656622 TI - Physical therapy guideline for children with malnutrition in low income countries: clinical commentary. AB - Physical therapy intervention along with nutritional rehabilitation has recently become an inevitable combo after recent evidences suggesting a strong interaction between malnutrition and neuro-muscular disabilities which contribute to a significant burden in global settings. Recent studies confirm that appropriate physical assessment of neuro-musculo skeletal system, developmental assessment or cognitive tools along with nutritional assessments followed by exercise rehabilitation will yield positive results in children with malnutrition. There is an obvious need to make available a simple physical therapy exercise guidelines with simple measure and exercise to be used in resource limited settings of developing countries. The purpose of this clinical commentary is to summarize simple assessment tools to evaluate activity impairment, participation restriction, gross motor activity and simple physical therapy intervention program for children with disability secondary to malnutrition. PMID- 27656623 TI - Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats. AB - Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2' deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3beta (GSK-3beta) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3beta expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3beta expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats. PMID- 27656624 TI - Treadmill exercise facilitates recovery of locomotor function through axonal regeneration following spinal cord injury in rats. AB - Spinal cord injury (SCI) disrupts both axonal pathways and segmental spinal cord circuity, resulting in permanent neurological deficits. Physical exercise is known to increase the expression of neurotrophins for improving the injured spinal cord. In the present study, we investigated the effects of treadmill exercise on locomotor function in relation with brain-derived neurotrophic factor (BDNF) expression after SCI. The rats were divided into five groups: control group, sham operation group, sham operation and exercise group, SCI group, and SCI and exercise group. The laminectomy was performed at the T9-T10 level. The exposed dorsal surface of the spinal cord received contusion injury (10 g * 25 mm) using the impactor. Treadmill exercise was performed 6 days per a week for 6 weeks. In order to evaluate the locomotor function of animals, Basso-Beattie Bresnahan (BBB) locomotor scale was conducted once a week for 6 weeks. We examined BDNF expression and axonal sprouting in the injury site of the spinal cord using Western blot analysis and immunofluorescence staining. SCI induced loss of locomotor function with decreased BDNF expression in the injury site. Treadmill exercise increased the score of BBB locomotor scale and reduced cavity formation in the injury site. BDNF expression and axonal sprouting within the trabecula were further facilitated by treadmill exercise in SCI-exposed rats. The present study provides the evidence that treadmill exercise may facilitate recovery of locomotor function through axonal regeneration via BDNF expression following SCI. PMID- 27656625 TI - Treadmill exercise ameliorates motor dysfunction through inhibition of Purkinje cell loss in cerebellum of valproic acid-induced autistic rats. AB - Autism is a complex developmental disorder with impairments in social interaction, communication, repetitive behavior and motor skills. Exercise enhances cognitive function, ameliorates motor dysfunction, and provides protective profits against neurodegeneration. In the present study, we evaluated the effect of treadmill exercise on the motor coordination and Purkinje cell loss in relation with reactive astrocytes and microglial activation in the cerebellum using valproic acid (VPA)-induced autism rat model. On the 12th day of pregnancy, the pregnant rats in the VPA-exposed group received intraperitoneal injections of 600-mg/kg VPA. After birth, the rat pups were divided into four groups: the control group, the exercise group, the VPA-treated group, the VPA-treated and exercise group. The rat pups in the exercise groups were forced to run on a treadmill for 30 min once a day, 5 times a week for 4 weeks. In the present results, motor balance and coordination was disturbed by induction of autism, in contrast, treadmill exercise alleviated motor dysfunction in the autistic rats. Purkinje cell loss, reactive astrocytes, and microglial activation were occurred by induction of autism, in contrast, treadmill exercise enhanced survival rate of Purkinje neurons through inhibition of reactive astrocytes and microglia in the autistic rats. The present study showed that exercise may provide a potential therapeutic strategy for the alleviation of motor dysfunction in autistic patients. PMID- 27656626 TI - Treadmill exercise ameliorates intracerebral hemorrhage-induced depression in rats. AB - Intracerebral hemorrhage (ICH) is a severe type of stroke causing neurological dysfunction with high mortality rate. Depression is one of the most common complications of ICH. In the present study, the effects of treadmill exercise on ICH-induced depressive symptoms in relation with apoptosis were investigated using rats. ICH rat model was induced by injection of collagenase into the hippocampus using stereotaxic instrument. Open field test for activity and forced swimming test for depressive symptoms were conducted. Apoptosis in the hippocampus was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3, and western blot for Bcl-2 and Bax. Western blot analysis for 5-hydroxy-tryptamine (5-HT, serotonin) and tryptophan hydroxylase (TPH) in the dorsal raphe was also conducted for biomarkers of depression. In the present results, immobility time was increased and climbing time was decreased by induction of ICH and treadmill exercise inhibited immobility time and increased climbing time in ICH rats. DNA fragmentation and caspase-3 expression in the hippocampal dentate gyrus were enhanced by induction of ICH and treadmill exercise suppressed ICH-induced DNA fragmentation and caspase-3 expression. Bax expression in the hippocampus was increased by induction of ICH and treadmill exercise inhibited Bax expression in the ICH rats. Expressions of 5-HT and TPH in the dorsal raphe were decreased by induction of ICH and treadmill exercise increased expressions of 5-HT and TPH in the ICH rats. In the present study, treadmill exercise ameliorated depressive symptoms through inhibiting apoptosis. PMID- 27656627 TI - The effects of compression garments and electrostimulation on athletes' muscle soreness and recovery. AB - In this study, we explained the effects of compression garment and electrostimulation on athletes' recovery period by evaluating blood lactate and isokinetic peak torque parameters. Twenty volunteers (15.55+/- 0.51 yr) were included to study. At recovery period, blood samples was taken for lactate values at 0th, 3rd, 5th, 15th, 30th min. The isokinetic strength test was performed on right ankle at 15th min and on the left ankle at 30th min. The same protocol was performed for compression garment on 2 weeks and for electrostimulation on third weeks and results were compared. There wasn't any significant difference on blood lactate levels within groups. At women; there was not any significant difference on isokinetic peak torques within two groups. but at electro-stimulation usage we found significant increases on right plantar flexion (P<0.1), right dorsal flexion (RDF) (P<0.1) and left plantar flexion (LPF) (P<0.1) values compared to control measurements. At men; with compression garment usage, there was significant increase on LPF values compared to control measurements. At electrostimulation usage, we found significant increases on RDF (P<0.1) and left dorsal flexion (P<0.1) values compared to control measurements. During recovery, there is not any beneficial effect seen on blood lactate level within two groups. When compared to passive rest, compression garments and electrostimulation interventions effects on force generation capacity at recovery are statically significant. Also in terms of force generation capacity; usage of electrostimulation during 15 min and compression garments during 30 min were statically more significant. PMID- 27656628 TI - Effects of Taekwondo intervention on balance in children with autism spectrum disorder. AB - The purpose of this study was to investigate the effects of an 8-week Taekwondo (TKD) intervention on balance in children with autism spec-trum disorder (ASD). A total of 14 children with ASD participated in this study. Eight children (eight males; mean age, 10.25+/-2.38 yr) completed TKD intervention (50 min/2 times/8 week), and six children received no intervention serving as controls (five males, one female; mean age, 10.00+/-2.83 yr). A computed posturography system with a long forceplate (NeuroCom Balance Master) was used to evaluate static (double and single leg stance with various test conditions) and functional balance (step quick-turn). Balance was measured before and after the intervention. A mixed model analysis of variance showed a significant group by time interaction in single leg stance balance. After the intervention, the TKD group displayed a greater improvement in single leg stance balance with eyes closed condition than the control group (P=0.046). Within-group analysis showed that the TKD group significantly improved single leg stance balance with eyes open condition (P=0.014). In addition, TKD group displayed trends of improvements in double leg stance balance with unstable surface under eyes closed condition (ES=0.83) and step-quick-turn (Cohen d [ES]=0.70). The control group did not show any significant changes in balance outcomes. In conclusion, TKD training can help children with ASD improve their balance. Children with ASD also showed a high rate of adherence (92%) to the TKD training. Our findings suggest that TKD can be a fun, feasible, and effective therapeutic option for balance improvement of children with ASD. PMID- 27656629 TI - Acute effects of aerobic stretching, health and happiness improving movement exercise on cortical activity of children. AB - Acute high-intensity physical exercise is known to improve cognitive performance of children, including those with attention-deficit/hyperactivity disorder (ADHD). In this work, we investigated the acute effect of an aerobic stretching and moderate-intensity, health and happiness improving movement (HHIM) exercise on the cortical activity of children with and without ADHD using electroencephalography (EEG). Children aged 12 to 14 yr with combined-type ADHD and age-matched healthy controls participated in the study, performing two individual movements (n=79, 35 controls) and a single exercise bout (n=45, 18 controls). electroencephalographic signals were recorded before and immediately after each movement, and before and after acute exercise under resting conditions, to obtain absolute and relative power estimates for the theta (3.5-8 Hz), alpha (8-12 Hz), sensory motor rhythm (12-16 Hz), and beta (16-25 Hz) bands. After acute HHIM exercise, all children showed significant changes in their relative EEG, mainly in the theta and alpha bands. Individual movements were found to influence relative theta, alpha and beta, and theta-to-beta ratios. He presents aerobic stretching HHIM exercise has demonstrated acute effect on the cortical activity of children. PMID- 27656630 TI - The effects of the academic performance of college students whose major is sports on body composition and abdominal fat rates. AB - The subjects of this research are 30 students of Dong-Eui Institute of Technology in Busan city, who were grouped into two categories after applying the curriculum of the second semester of the freshman year to their classes: those whose academic performance was at the top 20% (15 students) and those whose academic performance was at the bottom 20% (15 students). For the measurement items, we measured their weight, body fat mass, body fat rates, body mass index, and abdominal fat rates by using a body composition testing machine. We then analyzed the t-test results by using the IBM SPSS ver. 18.0 program. Through this research, we found that there was a significant difference among those in the group of students whose academic performance was at the top 20% in terms of body fat mass and body fat rates, which means that academic performance has relatively little effect on body composition and abdominal fat rates. PMID- 27656631 TI - Physical and functional follow-up of tuberculosis patients in initial intensive phase of treatment in Cameroon using the 6-min walk test. AB - This study aimed to evaluate functional capacities of Cameroonian tuberculosis (TB) patients in initial intensive phase of treatment using the 6-min walk test (6MWT) and to compare them to an age-matched healthy group. Twenty-eight TB patients newly diagnosed and 19 healthy age-matched peoples participated in the study. Performance parameters were determined using the 6MWT. Anthropometric and cardiorespiratory parameters were measured at baseline and after 6MWT. Two months later, TB patients were submitted to the same evaluation. We found significant differences in anthropometric parameters between the two groups. The baseline cardiorespiratory parameters and performance characteristics of TB patients were lower than control group (571.7+/-121.0 m vs 841.6+/-53.0 m, P<0.0001 for 6-min walk distance (6MWD) and 18.1+/-2.8 mL/kg/min vs 24.3+/-1.2 mL/kg/min, P<0.001 for mean VO2 peak (peak oxygen consumption). Two months after, significant improvements were noted in anthropometric, cardiorespiratory and performance parameters except for bone mass and FEV1/FEV6 (forced expiratory volumes in 1 second/6 seconds) ratio. Significant correlations were found between the 2-min walked distance (P<0.0001, r=0.95), 4-min walked distance (P<0.0001, r=0.97) and 6MWD. In conclusion, TB patients have impaired physical functional capacity but they improved after 2 months of treatment. 6MWT can be a useful tool in the assessment of physical parameters and cardiorespiratory functional capacity rehabilitation of TB patients during the treatment. PMID- 27656632 TI - Development and effect of a cognitive enhancement gymnastics program for elderly people with dementia. AB - The purpose of this study was to develop a cognitive enhancement gymnastics program for the elderly with dementia and to verify its effect. The study was conducted on 27 people with dementia being treated in a dementia day care center in Incheon city. No statistically significant differences were found in the measures Mini-Mental State Examination for Dementia Screening (MMSE-DS), Short Geriatric Depression Scale (SGDS), Seoul Activities of Daily Living (S-ADL), or rock-paper-scissors. However, the MMSE-DS and rock-paper-scissors showed improvement after 12 weeks. PMID- 27656634 TI - An exploration of implications for the development of Pilates instructor system through identification of instructors' difficulties. AB - This study is aimed at exploring ideas for the development of Pilates instructor qualification system by identifying a range of difficulties Pilates instructors are experiencing. Open-ended questionnaires and semi-structured interviews were conducted to collect data before they were analyzed with inductive content analysis method. In consideration of the difficulties Pilates instructors experience during three qualification stages (before-during-after qualification education), three key categories were incorporated in the collected data: (1) lack of information on Pilates qualification system, (2) difficulties in understanding the human anatomy related with the diverse movements taught in Pilates classes and its application to Pilates practice, (3) need for professional development through retraining. Based on these findings, a need for rethinking the monitoring and evaluation process for Pilates qualification system and Pilates education in Korea was identified. In addition, we need to summarize and offer information on a range of Pilates qualifications. And the quality of Pilates instructor education program should be improved as well by proving them a range of teaching methods including microteaching, discussion-based lessons as well as reading and writing sessions and other necessary teaching media. PMID- 27656633 TI - Influence of the actions observed on cervical motion in patients with chronic neck pain: a pilot study. AB - The aim of the present pilot study was to prove if the action-observation (AOb) improved the cervical range of motion (CROM) in patients with nonspecific chronic neck pain (CNP). Double blind pilot study. A total of 28 subjects were randomly assigned to an effective-movement group (n=14) and an ineffective-movement group (n=14). The follow-up consisted of: pretreatment, posttreatment and 10 min after second measurement (motor imagery). Outcome measures were CROM, and pres-sure pain detection thresholds (PPDTs). No statistical differences were found in baseline on CROM and on the PPDT. Test for independent groups revealed significant changes in cervical rotation movement. Both groups in posttreatment (P=0.042; Cohen d=0.81) and after 10 min (P=0.019; Cohen d=0.9). For intragroup PPDT, the Wilcoxon test revealed significant effects in the effective movement at C2 of the pre to 10-min post (P=0.040). However, the ineffective movement revealed a significant reduction in PPDT in zygapophyseal joint of C5-C6 as the pre to post (P=0.010) as the pre to 10-min post (P=0.041) periods. In conclusions this pilot study demonstrated that the effective AOb produced significant changes versus ineffective AOb in the CROM and it could influences in PPT in subject with CNP immediately. PMID- 27656635 TI - Evaluation of the accuracy of Lachman and Anterior Drawer Tests with KT1000 in the follow-up of anterior cruciate ligament surgery. AB - Ligament laxity measurement is clinically valuable to diagnose the injury and also to compare the laxity before and after surgical procedure. The aim of the study was to compare the accuracy of the Lachman and Anterior Drawer Tests to evaluate the knee examination with the KT1000 arthrometer after the anterior cruciate ligament (ACL) surgery in early follow-up period. Fourty ACL reconstructed knees were examined with the Lachman and Anterior Drawer Tests, and KT1000 arthrometer with compariable intact knee of the same patients. Physical emanination findings were compared with the KT1000 arthrometer with each power. Spearman correlation and receiver operating characteristic (ROC) analysis were used for the evaluation of relations between parameters. Significance was evaluated in P<0.1 and P<0.05. The mean age was 28.18+/-6.21 yr, and the mean follow-up was 23.09+/-9.08 months. The mean KT1000 measurements of 40 operated knees state at 6.8, 9.1, 13.6 kg and maxium anterior displacement forces were 4.9, 6.7, 8.7, and 11.9 mm, respectively. The same values for the same acting forces of intact knees were 4.2, 5.9, 7.8, and 10.2, respectively. In Spearman's correlation and ROC analysis at 13.6-kg power on KT1000 arthrometer statistically matched with pyhsical examinations (P<0.1, P<0.01). In our study, correlation of physical examinations with KT1000 arthrometer is a worthy evaluation technique that can be added to examination of ACL reconstructed knee to control with inexperinced examiners' findings. We suggest that at 13.6-kg power with KT1000 arthrometer findings perfectly match the Lachman and Anterior Drawer Tests of the knee. PMID- 27656636 TI - Effect of the kinetic variables and postural stability between bilateral in lower limbs by the Oreum trekking exercise: asymmetric index. AB - This study aimed to analyze an effect of the kinetic variables and postural stability between bilateral in lower limbs by participation of Oreum trekking exercise program and subjects participated were composed of adult male and female subjects (n=14) of 20s. Experiment was performed with the drop landing which can evaluate postural stability and kinetic variables between bilateral in lower limbs. peak vertical force (PVF) value showed significant difference with the less in case of post than before participation of Oreum trekking exercise. Also PVF of bilateral in lower limbs did not showed significant difference, and too the effect of interaction. vertical stability index (VSI) and dynamic postural stability index (DPSI) showed significant difference with improvement of postural stability by Oreum trekking, but did not between bilateral in the limbs. Particularly the result of one-way analysis of variance due to VSI's effect of interaction, showed the more influence on the improvement of postural stability in left leg after participation of Oreum trekking exercise. When consideration the above, the analysis result on asymmetric index of bilateral in lower limbs showed more symmetric pattern in post than before participation of Oreum trekking exercise program. PMID- 27656637 TI - Restrictions of physical activity participation in older adults with disability: employing keyword network analysis. AB - Older adults with disability might have been increasing due to the rapid aging of society. Many studies showed that physical activity is an essential part for improving quality of life in later lives. Regular physical activity is an efficient means that has roles of primary prevention and secondary prevention. However, there were few studies regarding older adults with disability and physical activity participation. The purpose of this current study was to investigate restriction factors to regularly participate older adults with disability in physical activity by employing keyword network analysis. Two hundred twenty-nine older adults with disability who were over 65 including aging with disability and disability with aging in type of physical disability and brain lesions defined by disabled person welfare law partook in the open questionnaire assessing barriers to participate in physical activity. The results showed that the keyword the most often used was 'Traffic' which was total of 21 times (3.47%) and the same proportion as in the 'personal' and 'economical'. Exercise was considered the most central keyword for participating in physical activity and keywords such as facility, physical activity, disabled, program, transportation, gym, discomfort, opportunity, and leisure activity were associated with exercise. In conclusion, it is necessary to educate older persons with disability about a true meaning of physical activity and providing more physical activity opportunities and decreasing inconvenience should be systematically structured in Korea. PMID- 27656638 TI - Assessment of Liver Stiffness in Pediatric Fontan Patients Using Transient Elastography. AB - Background. Hepatic fibrosis is a potential complication following Fontan surgery and heralds long-term risk for cirrhosis. Transient elastography (TE) is a rapid, noninvasive method to assess liver fibrosis by measuring liver stiffness. Objectives. To compare liver stiffness and liver biochemistries in pediatric Fontan patients with age- and sex-matched controls and to determine patients' acceptance of TE. Methods. Patients were recruited from British Columbia Children's Hospital. Twenty-two Fontan patients (15 males) were identified. Demographic information and cardiac data were collected. TE was measured using size-appropriate probes. Results. The median age of the Fontan cohort was 13.7 (5.9-16.8) years. Time from Fontan surgery to TE was 9.6 (1.0-12.9) years. The median Fontan circuit pressure was 13 (11-14) mmHg. TE values were higher in Fontan patients versus controls (18.6 versus 4.7 kPa, p < 0.001). There was no association between TE values and patient age (r = 0.41, p = 0.058), time since Fontan surgery (r = 0.40, p = 0.062), or median Fontan circuit pressure (CVP) (r = 0.35, p = 0.111). Patients found TE to be nonpainful, convenient, and safe. Conclusions. TE is feasible to assess liver stiffness in children following Fontan surgery. Pediatric Fontan patients have markedly elevated liver stiffness values. TE may have important utility in liver care follow-up of pediatric Fontan patients. PMID- 27656639 TI - Physical Activity Participation of Disabled Children: A Systematic Review of Conceptual and Methodological Approaches in Health Research. AB - Physical activity (PA) participation is widely recognized as a critical component of health and development for disabled and non-disabled children. Emergent literature reflects a paradigm shift in the conceptualization of childhood PA as a multi-dimensional construct, encompassing aspects of physical performance, and self-perceived engagement. However, ambiguity remains around how participation as a health construct is integrated into PA research. The primary objective of the present mini-review is to critically examine current conceptual and methodological approaches to evaluating PA participation among disabled children. We conducted a systematic review of contemporary literature (published between 2000 and 2016). Seventeen articles met inclusion criteria, and their research approach was classified into guiding framework, definition of the key construct, and measurement used. The primary guiding framework was the international classification of functioning, disability and health. An explicit definition of PA participation was absent from all studies. Eight studies (47%) operationalized PA and participation as independent constructs. Measurements included traditional performance-based aspects of PA (frequency, duration, and intensity), and alternative participation measures (subjective perception of involvement, inclusion, or enjoyment). Approximately 64% of included articles were published in the past 2 years (2014-2016) indicating a rising interest in the topic of PA participation. Drawing from the broader discussion of participation in the literature, we offer a working definition of PA participation as it pertains to active, health-associated behaviors. Further description of alternative approaches to framing and measuring PA participation are offered to support effective assessment of health status among disabled children. PMID- 27656640 TI - Predictors of Participation in Mammography Screening among Non-Hispanic Black, Non-Hispanic White, and Hispanic Women. AB - INTRODUCTION: Many factors influence women's decisions to participate in guideline-recommended screening mammography. We evaluated the influence of women's socioeconomic characteristics, health-care access, and cultural and psychological health-care preferences on timely mammography screening participation. MATERIALS AND METHODS: A random digit dial survey of United States non-Hispanic Black, non-Hispanic White, and Hispanic women aged 40-75, from January to August 2009, determined self-reported time of most recent mammogram. Screening rates were assessed based on receipt of a screening mammogram within the prior 12 months, the interval recommended at the time by the American Cancer Society. RESULTS: Thirty-nine percent of women reported not having a mammogram within the last 12 months. The odds of not having had a screening mammography were higher for non-Hispanic White women than for non-Hispanic Black (OR = 2.16, 95% CI = 0.26, 0.82, p = 0.009) or Hispanic (OR = 4.17, 95% CI = 0.12, 0.48, p = 0.01) women. Lack of health insurance (OR = 3.22, 95% CI = 1.54, 6.73, p = 0.002) and lack of usual source of medical care (OR = 3.37, 95% CI = 1.43, 7.94, p = 0.01) were associated with not being screened as were lower self-efficacy to obtain screening (OR = 2.43, 95% CI = 1.26, 4.73, p = 0.01) and greater levels of religiosity and spirituality (OR = 1.42, 95% CI = 1.00, 2.00, p = 0.05). Neither perceived risk nor present temporal orientation was significant. DISCUSSION: Odds of not having a mammogram increased if women were uninsured, without medical care, non-Hispanic White, older in age, not confident in their ability to obtain screening, or held passive or external religious/spiritual values. Results are encouraging given racial disparities in health-care participation and suggest that efforts to increase screening among minority women may be working. PMID- 27656641 TI - The Use of Signal-Transduction and Metabolic Pathways to Predict Human Disease Targets from Electric and Magnetic Fields Using in vitro Data in Human Cell Lines. AB - Using in vitro data in human cell lines, several research groups have investigated changes in gene expression in cellular systems following exposure to extremely low frequency (ELF) and radiofrequency (RF) electromagnetic fields (EMF). For ELF EMF, we obtained five studies with complete microarray data and three studies with only lists of significantly altered genes. Likewise, for RF EMF, we obtained 13 complete microarray datasets and 5 limited datasets. Plausible linkages between exposure to ELF and RF EMF and human diseases were identified using a three-step process: (a) linking genes associated with classes of human diseases to molecular pathways, (b) linking pathways to ELF and RF EMF microarray data, and (c) identifying associations between human disease and EMF exposures where the pathways are significantly similar. A total of 60 pathways were associated with human diseases, mostly focused on basic cellular functions like JAK-STAT signaling or metabolic functions like xenobiotic metabolism by cytochrome P450 enzymes. ELF EMF datasets were sporadically linked to human diseases, but no clear pattern emerged. Individual datasets showed some linkage to cancer, chemical dependency, metabolic disorders, and neurological disorders. RF EMF datasets were not strongly linked to any disorders but strongly linked to changes in several pathways. Based on these analyses, the most promising area for further research would be to focus on EMF and neurological function and disorders. PMID- 27656642 TI - Fluorescence In situ Hybridization: Cell-Based Genetic Diagnostic and Research Applications. AB - Fluorescence in situ hybridization (FISH) is a macromolecule recognition technology based on the complementary nature of DNA or DNA/RNA double strands. Selected DNA strands incorporated with fluorophore-coupled nucleotides can be used as probes to hybridize onto the complementary sequences in tested cells and tissues and then visualized through a fluorescence microscope or an imaging system. This technology was initially developed as a physical mapping tool to delineate genes within chromosomes. Its high analytical resolution to a single gene level and high sensitivity and specificity enabled an immediate application for genetic diagnosis of constitutional common aneuploidies, microdeletion/microduplication syndromes, and subtelomeric rearrangements. FISH tests using panels of gene-specific probes for somatic recurrent losses, gains, and translocations have been routinely applied for hematologic and solid tumors and are one of the fastest-growing areas in cancer diagnosis. FISH has also been used to detect infectious microbias and parasites like malaria in human blood cells. Recent advances in FISH technology involve various methods for improving probe labeling efficiency and the use of super resolution imaging systems for direct visualization of intra-nuclear chromosomal organization and profiling of RNA transcription in single cells. Cas9-mediated FISH (CASFISH) allowed in situ labeling of repetitive sequences and single-copy sequences without the disruption of nuclear genomic organization in fixed or living cells. Using oligopaint-FISH and super-resolution imaging enabled in situ visualization of chromosome haplotypes from differentially specified single-nucleotide polymorphism loci. Single molecule RNA FISH (smRNA-FISH) using combinatorial labeling or sequential barcoding by multiple round of hybridization were applied to measure mRNA expression of multiple genes within single cells. Research applications of these single molecule single cells DNA and RNA FISH techniques have visualized intra nuclear genomic structure and sub-cellular transcriptional dynamics of many genes and revealed their functions in various biological processes. PMID- 27656644 TI - Repair of Perineal Hernia Following Abdominoperineal Excision with Biological Mesh: A Systematic Review. AB - INTRODUCTION: Perineal hernia (PerH) following abdominoperineal excision (APE) procedure is a recognized complication. PerH was considered an infrequent complication of APE procedure; however, PerH rates of up to 45% have been reported in recent publications following a laparoscopic APE procedure. Various methods of repair of PerH with the use of synthetic meshes or myocutaneous flap have been described, although there is no general agreement on an optimal strategy. The use of biological meshes for different operations is growing in popularity, and these have been promoted as being superior and safer when compared to synthetic meshes. Although the use of biologics is becoming popular claims of better outcomes are largely unsupported by evidence. The aim of this systematic review is to evaluate the currently available evidence supporting the use of biologic or biosynthetic meshes for the repair of PerH that develop following an APE. METHODS: A systematic review of all English language literature relevant to repair of PerH following APE with biologic or biosynthetic mesh published between January 1, 2000 and July 31, 2016 was carried out using MEDLINE, EMBASE, and the Cochrane Library of Systematic Reviews for relevant literature. Searches were performed using a combination of Medical Subject Headings (MeSH) terms and text words "PerH," "APE," "morbidity," "biologics," "biosynthetic," and "hernia." Studies in which the use of biological meshes was not reported were excluded from the review. Various outcome measures, including operative technique, complication rates, recurrence rates, type of mesh, management of recurrences, and risk factors, were extracted. Oxford Centre for Evidence-based Medicine - Levels of Evidence (March 2009) was used to assess the quality of evidence. RESULTS: The systematic review of the literature identified three case reports, four case series, and one pooled analysis that were included in the final review. Overall, these studies were of poor quality providing level 4 evidence. Various different approaches and techniques of repair of PerH were described; however, it was difficult to extract information with regard to the primary and secondary outcome measures. CONCLUSION: There is no general agreement to the optimal operative strategy to repair PerH following an APE. There is insufficient evidence to recommend any specific operative approach or repair technique for PerH following an APE. PMID- 27656643 TI - The Immunomodulatory Functions of Diacylglycerol Kinase zeta. AB - The generation of diacylglycerol (DAG) is critical for promoting immune cell activation, regulation, and function. Diacylglycerol kinase zeta (DGKzeta) serves as an important negative regulator of DAG by enzymatically converting DAG into phosphatidic acid (PA) to shut down DAG-mediated signaling. Consequently, the loss of DGKzeta increases DAG levels and the duration of DAG-mediated signaling. However, while the enhancement of DAG signaling is thought to augment immune cell function, the loss of DGKzeta can result in both immunoactivation and immunomodulation depending on the cell type and function. In this review, we discuss how different immune cell functions can be selectively modulated by DGKzeta. Furthermore, we consider how targeting DGKzeta can be potentially beneficial for the resolution of human diseases by either promoting immune responses important for protection against infection or cancer or dampening immune responses in immunopathologic conditions such as allergy and septic shock. PMID- 27656645 TI - Magnetic Resonance Imaging-Guided Treatment of Equine Distal Interphalangeal Joint Collateral Ligaments: 2009-2014. AB - OBJECTIVES: To determine the outcome of treating distal interphalangeal joint collateral ligament (DIJCL) desmopathy using magnetic resonance imaging (MRI) guided ligament injection. METHODS: Medical records of 13 adult horses diagnosed with DIJCL desmopathy using low-field MRI and treated by MRI-guided ligament injection of mesenchymal stem cells and/or platelet-rich plasma (PRP) were reviewed. Information collected included signalment, MRI diagnosis, treatment type, time to resolution of lameness, and level of exercise after treatment. RESULTS: Collateral ligament inflammation was diagnosed as a cause of lameness in 13 horses. MRI was used to guide the injection of the injured DIJCL. All lameness attributed to DIJCL desmopathy resolved with the resulting level of performance at expected (10) or less than expected (3). CONCLUSION AND CLINICAL RELEVANCE: Injection of the DIJCL can be safely completed in horses standing in a low-field magnet guided by MRI as previously demonstrated in cadaver specimens. The positive response in all horses suggests that administration of stem cells or PRP along with rest and appropriate shoeing may be a safe and useful treatment for DIJCL desmopathy. PMID- 27656646 TI - General Commentary on: Alternatives to Antibiotic Growth Promoters in Animals. PMID- 27656647 TI - Pharmacokinetic/Pharmacodynamic Profiles of Tiamulin in an Experimental Intratracheal Infection Model of Mycoplasma gallisepticum. AB - Mycoplasma gallisepticum is the most important pathogen in poultry among four pathogenic Mycoplasma species. Tiamulin is a pleuromutilin antibiotic that shows a great activity against M. gallisepticum and has been approved for use in veterinary medicine particularly for poultry. However, the pharmacokinetic/pharmacodynamics (PK/PD) profiles of tiamulin against M. gallisepticum are not well understood. Therefore, in the current studies, we investigated the in vivo PK/PD profiles of tiamulin using a well-established experimental intratracheal infection model of M. gallisepticum. The efficacy of tiamulin against M. gallisepticum was studied in 8-day-old chickens after intramuscular (i.m.) administration at 10 doses between 0-80 mg/kg. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to evaluate the PK parameters of tiamulin following i.m. administration at doses of 5, 40, and 80 mg/kg in Mycoplasma gallisepticum-infected neutropenic chickens. Real-time PCR (RT-PCR) was used for quantitative detection of M. gallisepticum. The MIC of tiamulin against M. gallisepticum strain S6 was 0.03 MUg/mL. The PK/PD index, AUC24h/MIC, correlated well with the in vivo antibacterial efficacy. The in vivo data suggest that animal dosage regimens should supply AUC24h/MIC of tiamulin of 382.68 h for 2 log10 ccu equivalents M. gallisepticum reduction. To attain that goal, the administered dose is expected to be 45 mg/kg b.w. for treatment of M. gallisepticum infection with an MIC90 of 0.03 MUg/mL. PMID- 27656648 TI - Clinical Application of a Modular Genomics Technique in Systemic Lupus Erythematosus: Progress towards Precision Medicine. AB - Monitoring disease activity in a complex, heterogeneous disease such as lupus is difficult. Both over- and undertreatment lead to damage. Current standard of care serologies are unreliable. Better measures of disease activity are necessary as we move into the era of precision medicine. We show here the use of a data driven, modular approach to genomic biomarker development within lupus specifically lupus nephritis. PMID- 27656649 TI - The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD. AB - Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor beta (TGF-beta) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-beta, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker alpha-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-beta in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-beta signaling in the pathogenesis of COPD, which warrants further investigation. PMID- 27656650 TI - Prosexual Effect of Chrysactinia mexicana A. Gray (Asteraceae), False Damiana, in a Model of Male Sexual Behavior. AB - Chrysactinia mexicana A. Gray (Asteraceae) and Turnera diffusa Willd (Turneraceae) are employed in traditional medicine as aphrodisiacs; however, there is no scientific evidence supporting the prosexual properties of C. mexicana. The aim of this study was to determine whether an aqueous extract of C. mexicana (Cm) stimulates rat male sexual behavior in the sexual exhaustion paradigm. Sexually exhausted (SExh) male rats were treated with Cm (80, 160, and 320 mg/kg), an aqueous extract of T. diffusa (Td), or yohimbine. The sexual exhaustion state in the control group was characterized by a low percentage of males exhibiting mounts, intromissions, and ejaculations and no males demonstrating mating behavior after ejaculation. Cm (320 mg/kg), Td, or yohimbine significantly increased the proportion of SExh rats that ejaculated and resumed copulation after ejaculation. In males that exhibited reversal of sexual exhaustion, Cm (320 mg/kg) improved sexual performance by reducing the number of intromissions and shrinking ejaculation latency. The effects of treatments on sexual behavior were not related with alterations in general locomotion. In conclusion, the prosexual effects of Cm, as well as those of Td, are established at a central level, which supports the traditional use of C. mexicana for stimulating sexual activity. PMID- 27656652 TI - Extracellular Ribonuclease from Bacillus licheniformis (Balifase), a New Member of the N1/T1 RNase Superfamily. AB - The N1/T1 RNase superfamily comprises enzymes with well-established antitumor effects, such as ribotoxins secreted by fungi, primarily by Aspergillus and Penicillium species, and bacterial RNase secreted by B. pumilus (binase) and B. amyloliquefaciens (barnase). RNase is regarded as an alternative to classical chemotherapeutic agents due to its selective cytotoxicity towards tumor cells. New RNase with a high degree of structural similarity with binase (73%) and barnase (74%) was isolated and purified from Bacillus licheniformis (balifase, calculated molecular weight 12421.9 Da, pI 8.91). The protein sample with enzymatic activity of 1.5 * 106 units/A280 was obtained. The physicochemical properties of balifase are similar to those of barnase. However, in terms of its gene organization and promoter activity, balifase is closer to binase. The unique feature of balifase gene organization consists in the fact that genes of RNase and its inhibitor are located in one operon. Similarly to biosynthesis of binase, balifase synthesis is induced under phosphate starvation; however, in contrast to binase, balifase does not form dimers under natural conditions. We propose that the highest stability of balifase among analyzed RNase types allows the protein to retain its structure without oligomerization. PMID- 27656653 TI - Improved Efficiency and Reliability of NGS Amplicon Sequencing Data Analysis for Genetic Diagnostic Procedures Using AGSA Software. AB - Screening for BRCA mutations in women with familial risk of breast or ovarian cancer is an ideal situation for high-throughput sequencing, providing large amounts of low cost data. However, 454, Roche, and Ion Torrent, Thermo Fisher, technologies produce homopolymer-associated indel errors, complicating their use in routine diagnostics. We developed software, named AGSA, which helps to detect false positive mutations in homopolymeric sequences. Seventy-two familial breast cancer cases were analysed in parallel by amplicon 454 pyrosequencing and Sanger dideoxy sequencing for genetic variations of the BRCA genes. All 565 variants detected by dideoxy sequencing were also detected by pyrosequencing. Furthermore, pyrosequencing detected 42 variants that were missed with Sanger technique. Six amplicons contained homopolymer tracts in the coding sequence that were systematically misread by the software supplied by Roche. Read data plotted as histograms by AGSA software aided the analysis considerably and allowed validation of the majority of homopolymers. As an optimisation, additional 250 patients were analysed using microfluidic amplification of regions of interest (Access Array Fluidigm) of the BRCA genes, followed by 454 sequencing and AGSA analysis. AGSA complements a complete line of high-throughput diagnostic sequence analysis, reducing time and costs while increasing reliability, notably for homopolymer tracts. PMID- 27656651 TI - Roles of Rack1 Proteins in Fungal Pathogenesis. AB - Pathogenic fungi cause diseases on various organisms. Despite their differences in life cycles, fungal pathogens use well-conserved proteins and pathways to regulate developmental and infection processes. In this review, we focus on Rack1, a multifaceted scaffolding protein involved in various biological processes. Rack1 is well conserved in eukaryotes and plays important roles in fungi, though limited studies have been conducted. To accelerate the study of Rack1 proteins in fungi, we review the functions of Rack1 proteins in model and pathogenic fungi and summarize recent progress on how Rack1 proteins are involved in fungal pathogenesis. PMID- 27656654 TI - Osteopontin Promotes Expression of Matrix Metalloproteinase 13 through NF-kappaB Signaling in Osteoarthritis. AB - Osteopontin (OPN) is associated with the severity and progression of osteoarthritis (OA); however, the mechanism of OPN in the pathogenesis of OA is unknown. In this study, we found that OA patients had higher abundance of OPN and matrix metalloproteinase 13 (MMP13). In chondrocytes, we showed that OPN promoted the production of MMP13 and activation of NF-kappaB pathway by increasing the abundance of p65 and phosphorylated p65 and translocation of p65 protein from cytoplasm to nucleus. Notably, inhibition of NF-kappaB pathway by inhibitor suppressed the production of MMP13 induced by OPN treatment. In conclusion, OPN induces production of MMP13 through activation of NF-kappaB pathway. PMID- 27656655 TI - Hypothyroidism Affects Olfactory Evoked Potentials. AB - Background. Objective electrophysiological methods for investigations of the organ of smell consist in recordings of olfactory cortex responses to specific, time restricted odor stimuli. In hypothyroidism have impaired sense of smell. Material and Methods. Two groups: control of 31 healthy subjects and study group of 21 with hypothyroidism. The inclusion criterion for the study group was the TSH range from 3.54 to 110 MUIU/mL. Aim. Assessment of the latency time of evoked responses from the olfactory nerve N1 and the trigeminal nerve N5 using two smells of mint and anise in hypothyroidism. Results. The smell perception in subjective olfactory tests was normal in 85% of the hypothyroid group. Differences were noticed in the objective tests. The detailed intergroup analysis of latency times of recorded cortical responses PN5 and PN1 performed by means between the groups of patients with overt clinical hypothyroidism versus subclinical hypothyroidism demonstrated a significant difference (p < 0.05) whereas no such differences were found between the control group versus subclinical hypothyroidism group (p > 0.05). Conclusion. We can conclude that registration of cortex potentials at irritation of olfactory and trigeminal nerves offers possibilities for using this method as an objective indicator of hypothyroidism severity and prognostic process factor. PMID- 27656656 TI - Charcot Neuropathic Arthropathy of the Foot: A Literature Review and Single Center Experience. AB - Charcot neuropathic osteoarthropathy of the foot is a relatively common complication of diabetic neuropathy. Incorrect diagnosis and improper treatment often result in the extremity having to be amputated. This paper summarises the current view on the etiology, diagnostics, and treatment of diabetic Charcot neuropathic osteoarthropathy, with particular focus on preserving the extremity through surgical intervention from our own experiences. PMID- 27656657 TI - Exendin-4 Promotes Survival of Mouse Pancreatic beta-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway. AB - Type 2 diabetes is a heterogeneous disorder that develops as a result of relatively inappropriate insulin secretion and insulin resistance. Increased levels of free fatty acids (FFAs) are one of the important factors for the pathogenesis of type 2 diabetes and contribute to defective beta-cell proliferation and increased beta-cell apoptosis. Recently, glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to possess an antiapoptotic effect, by increasing beta-cell mass and improving beta-cell function. However, their effects on beta-cells in vitro against lipotoxicity have not been elucidated completely. In this study, we investigated whether the GLP-1 receptor agonist exendin-4 displays prosurvival effects in pancreatic beta-cells exposed to chronic elevated FFAs. Results showed that exendin-4 inhibited apoptosis induced by palmitate in MIN6 cells. After 24 h of incubation, exendin-4 caused rapid activation of extracellular signal-related kinase 1/2 (ERK1/2) under lipotoxic conditions. The ERK1/2 inhibitor PD98059 blocked the antilipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis. This inhibition is associated with upregulation of BCL-2. Our findings suggested that exendin-4 may exert cytoprotective effects through activation of ERK1/2 and inhibition of the mitochondrial apoptosis pathway. PMID- 27656658 TI - Patient Activation in Type 2 Diabetes: Does It Differ between Men and Women? AB - Background. Aim was to investigate whether the degree of patient activation of patients with type 2 diabetes (T2D) is different between men and women. Furthermore, we investigated which factors are associated with patient activation in men and women. Methods. This cross-sectional study included 1615 patients with T2D from general practices. Patient activation was measured with the Patient Activation Measure (PAM) questionnaire. Multivariate linear regression analyses were used to investigate the association between gender and patient activation. Stratified analyses according to gender were performed to investigate which factors are associated with patient activation. Results. No association between gender and PAM score was found after adjustment for all selected confounders (p = 0.094). In men, lower age (p = 0.001), a higher WHO-5 score (p < 0.001), and a lower BMI (p = 0.013) were associated with a higher PAM score. In women, a higher WHO-5 score (p < 0.017) and the absence of macrovascular complications (p < 0.031) were associated with a higher PAM score. Conclusion. There is no difference in the degree of patient activation of men and women with T2D. Age, well-being, and BMI were found to be associated with patient activation in men, whereas well-being and macrovascular complications were found to be associated with patient activation in women. PMID- 27656659 TI - The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning. AB - Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning. PMID- 27656660 TI - Severe Babesia microti Infection in an Immunocompetent Host in Pennsylvania. AB - Babesiosis, due to infection by a tick-borne protozoan (predominantly Babesia microti in North America), is an emerging health risk that is expanding into new areas and may be unfamiliar to clinicians in locations not previously considered endemic. Manifestations of infection can range from asymptomatic to life threatening, with severe disease more likely in those who have had a splenectomy, are immunocompromised, have chronic medical conditions, or are over 50 years of age. In this article, we describe an elderly but otherwise healthy man from an area not generally considered endemic for babesiosis who presented with severe hemolysis, acute renal failure, and high-level Babesia microti parasitemia; serological results suggestive of possible coinfection by Borrelia burgdorferi (the agent of Lyme disease, which is carried by the same tick as is Babesia microti) also was found. This report highlights that severe babesiosis can occur in an apparently normal host and underscores the continued geographic expansion of this pathogen and the need for early recognition and therapy. PMID- 27656661 TI - A multiple sclerosis-like disorder in patients with OPA1 mutations. AB - We describe three unrelated patients presenting with a spinal cord syndrome and neuroimaging features consistent with multiple sclerosis (MS). All harbored a pathogenic OPA1 mutation. Although the neurological phenotype resembled neuromyelitis optica (NMO), anti-aquaporin 4 antibodies were not detected and the disorder followed a slow progressive course. The coincidental occurrence of OPA1 mutations and an MS-like disorder is likely to have modulated the phenotypic manifestations of both disorders, but unlike the previously reported association of Leber hereditary optic neuropathy and MS (Harding disease), the optic neuropathy in patients with OPA1 mutations and an MS-like disorder can be mild with a good visual prognosis. PMID- 27656662 TI - Global proteomics dataset of miR-126 overexpression in acute myeloid leukemia. AB - A deep proteomics analysis was conducted on a primary acute myeloid leukemia culture system to identify potential protein targets regulated by miR-126. Leukemia cells were transduced either with an empty control lentivirus or one containing the sequence for miR-126, and resulting cells were analyzed using ultra-high performance liquid chromatography (UHPLC) coupled with high resolution mass spectrometry. The mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE: PXD001994. The proteomics data and statistical analysis described in this article is associated with a research article, "miR-126 regulates distinct self-renewal outcomes in normal and malignant hematopoietic stem cells" (Lechman et al., 2016) [1], and serves as a resource for researchers working in the field of microRNAs and their regulation of protein levels. PMID- 27656664 TI - Data supporting the co-expression of PDHA1 gene and of its paralogue PDHA2 in somatic cells of a family. AB - This article presents a dataset proving the simultaneous presence of a 5'UTR truncated PDHA1 mRNA and a full-length PDHA2 mRNA in the somatic cells of a PDC deficient female patient and all members of her immediate family (parents and brother). We have designed a large set of primer pairs in order to perform detailed RT-PCR assays allowing the clear identification of both PDHA1 and PDHA2 mRNA species in somatic cells. In addition, two different experimental approaches were used to elucidate the copy number of PDHA1 gene in the patient and her mother. The interpretation and discussion of these data, along with further extensive experiments concerning the origin of this altered gene expression and its potential therapeutic consequences, can be found in "Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: null mutations in the PDHX gene associated with unusual expression of the testis specific PDHA2 gene in her somatic cells" (A. Pinheiro, M.J. Silva, C. Florindo, et al., 2016) [1]. PMID- 27656663 TI - Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer's disease. AB - This data article contains supporting information regarding the research article entitled "Traumatic brain injury accelerates amyloid-beta deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease" (H. Shishido, Y. Kishimoto, N. Kawai, Y. Toyota, M. Ueno, T. Kubota, Y. Kirino, T. Tamiya, 2016) [1]. Triple-transgenic (3*Tg)-Alzheimer's disease (AD) model mice exhibited significantly poorer spatial learning than sham-treated 3*Tg-AD mice 28 days after traumatic brain injury (TBI). Correspondingly, amyloid-beta (Abeta) deposition within the hippocampus was significantly greater in 3*Tg-AD mice 28 days after TBI. However, data regarding the short-term and long-term influences of TBI on amyloid precursor protein (APP) accumulation in AD model mice remain limited. Furthermore, there is little data showing whether physical activity and motor learning are affected by TBI in AD model mice. Here, we provide immunocytochemistry data confirming that TBI induces significant increases in APP accumulation in 3*Tg-AD mice at both 7 days and 28 days after TBI. Furthermore, 3*Tg-AD model mice exhibit a reduced ability to acquire conditioned responses (CRs) during delay eyeblink conditioning compared to sham-treated 3*Tg-AD model mice 28 days after TBI. However, physical activity and motor performance are not significantly changed in TBI-treated 3*Tg-AD model mice. PMID- 27656665 TI - Data on some qualitative parameters of Carolea olive oils obtained in different areas of Calabria (Southern Italy). AB - This data article contains complementary results related to the paper "Characterization of monovarietal olive oils obtained from mills of Calabria region (Southern Italy)" (Piscopo et al., 2016) [1]. Data was obtained by capillary-column gas chromatography, analyzing sterols and triterpene dialcohols and ethyl esters in the composition of Carolea olive oils. They were produced in different areas of Calabria region (Southern Italy), named: the Sibari's plateau (SP), the Valley of Sant' Eufemia (VSE), the Tyrrhenian southern area (TSA), the Ionian southern coast (ISC) and the Ionian area of Catanzaro (IAC). Specifically the characterized samples were 24 in the SP; 43 in the VSE; 15 in the TSA; 30 in the ISC, and 34 in the IAC, for a total amount of 146 olive oils. The differences in some compositional characteristics denoted the effect of the environmental and could be considered to improve the local productions. The compilation of this data provides a resource for the wider research community and the interpretation of this data could be found in the research article noted above. PMID- 27656666 TI - Data of expression and purification of recombinant Taq DNA polymerase. AB - Polymerase chain reaction (PCR) technique is widely used in many experimental conditions, and Taq DNA polymerase is critical in PCR process. In this article, the Taq DNA polymerase expression plasmid is reconstructed and the protein product is obtained by rapid purification, ("Rapid purification of high-activity Taq DNA polymerase" (Pluthero, 1993 [1]), "Single-step purification of a thermostable DNA polymerase expressed in Escherichia coli" (Desai and Pfaffle, 1995 [2])). Here we present the production data from protein expression and provide the analysis results of the production from two different vectors. Meanwhile, the purification data is also provided to show the purity of the protein product. PMID- 27656667 TI - A synthetic Longitudinal Study dataset for England and Wales. AB - This article describes the new synthetic England and Wales Longitudinal Study 'spine' dataset designed for teaching and experimentation purposes. In the United Kingdom, there exist three Census-based longitudinal micro-datasets, known collectively as the Longitudinal Studies. The England and Wales Longitudinal Study (LS) is a 1% sample of the population of England and Wales (around 500,000 individuals), linking individual person records from the 1971 to 2011 Censuses. The synthetic data presented contains a similar number of individuals to the original data and accurate longitudinal transitions between 2001 and 2011 for key demographic variables, but unlike the original data, is open access. PMID- 27656668 TI - Characterization, kinetic, and isotherm data for Cr (VI) removal from aqueous solution by Populus alba biochar modified by a cationic surfactant. AB - Populus alba is fast and auto- growing tree which profoundly accessible in around the world. The usage of the wastes of this tree would be admirable from environmental and solid waste management point of view. Thus, herein, this data set presents a facile method for providing an adsorbent from wastes of P. alba tree. The prepared adsorbent was modified by the cationic surfactant of (C16H33)N(CH3)3Br and applied to remove Cr (VI) from aqueous solution. The characterization data of the modified adsorbent were analyzed using FTIR and SEM methods. The information regarding kinetics, isotherms, and thermodynamics of chromium ions adsorption were listed. The data implied that the maximum adsorption capacity of adsorbent to uptake Cr (VI) from aqueous solution was obtained 52.63 mg/g. The acquired data indicated that the adsorption of Cr (VI) by the adsorbent prepared from P. alba is an promising technique for treating Cr bearing wastewaters. PMID- 27656669 TI - Data generated from three quantitative mass spectral methods for the analysis of trivalent influenza vaccine antigens are compared. AB - Herein we present the data necessary for generation of alternative means to produce equimolar mixtures of peptides ("Design and Expression of a QconCAT Protein to Validate Hi3 Protein Quantification of Influenza Vaccine Antigens" (D.G.S. Smith, G. Gingras, Y. Aubin, T.D. Cyr, 2016) [1]), such as QConCAT ("Trends in QconCATs for targeted proteomics" (J. Chen, I.V. Turko, 2014) [2] , "Natural flanking sequences for peptides included in a quantification concatamer internal standard" (C.S. Cheung, K.W. Anderson, M. Wang, I.V. Turko, 2015) [3]) and SpikeTides versus the label free Hi3 approach. The experimental design and the interpretation of results are discussed in the original article [1]. PMID- 27656670 TI - Morphological and optical data of AgNW embedded transparent conductive layer. AB - In this data article, morphological and optical data of AgNW encapsulated between ITO layers are presented to get insights into our article (DOI:10.1016/j.solmat.2016.04.038; Hong-Sik Kim, Pankaj Yadav, Malkeshkumar Patel, Hyunki Kim, Kavita Pandey, Joondong Kim, 2016) [1]. SEM images for the formation of AgNWs networks by number of spin coating are also presented. SEM photographs showing the surface morphologies before and after rapid thermal treatment of prepared samples have been presented. Apart from morphological data set, optical characteristics of this type of samples are given. The comparison plots of optical reflectance from AgNW encapsulated between ITO layers and bare ITO are given between the wavelength ranges from 300 to 1100 nm. At the end, transmittance and reflectance curves of native glass substrates used in this study are presented. PMID- 27656671 TI - Time perspective and well-being: Swedish survey questionnaires and data. AB - The data pertains 448 Swedes' responses to questionnaires on time perspective (Zimbardo Time Perspective Inventory), temporal life satisfaction (Temporal Satisfaction with Life Scale), affect (Positive Affect and Negative Affect Schedule), and psychological well-being (Ryff's Scales of Psychological Well Being-short version). The data was collected among university students and individuals at a training facility (see U. Sailer, P. Rosenberg, A.A. Nima, A. Gamble, T. Garling, T. Archer, D. Garcia, 2014; [1]). Since there were no differences in any of the other background variables, but exercise frequency, all subsequent analyses were conducted on the 448 participants as one single sample. In this article we include the Swedish versions of the questionnaires used to operationalize the time perspective and well-being variables. The data is available, SPSS file, as Supplementary material in this article. We used the Expectation-Maximization Algorithm to input missing values. Little's Chi-Square test for Missing Completely at Random showed a chi (2)=67.25 (df=53, p=.09) for men and chi (2)=77.65 (df=72, p=.31) for women. These values suggested that the Expectation-Maximization Algorithm was suitable to use on this data for missing data imputation. PMID- 27656672 TI - Dataset of differentially expressed genes from SOX9 over-expressing NT2/D1 cells. AB - The data presents the genes that are differentially up-regulated or down regulated in response to SOX9 in a human Sertoli-like cell line, NT2/D1. The dataset includes genes that may be implicated in gonad development and are further explored in our associated article, "SOX9 Regulates Expression of the Male Fertility Gene Ets Variant Factor 5 (ETV5) during Mammalian Sex Development" (D. lankarage, R. Lavery, T. Svingen, S. Kelly, L.M. Ludbrook, S. Bagheri-Fam, et al., 2016) [1]. The necessity of SOX9 for male sex development is evident in instances where SOX9 is lost, as in 46, XY DSD where patients are sex reversed or in mouse knock-out models, where mice lacking Sox9 are sex reversed. Despite the crucial nature of this transcriptional activator, downstream target genes of SOX9 remain largely undiscovered. Here, we have utilized NT2/D1 cells to transiently over-express SOX9 and performed microarray analysis of the RNA. Microarray data are available in the ArrayExpress database (www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-3378. PMID- 27656673 TI - Data on the oral CRTh2 antagonist QAW039 (fevipiprant) in patients with uncontrolled allergic asthma. AB - This article contains data on clinical endpoints (Peak Flow Expiratory Rate, fractional exhaled nitric oxide and total IgE serum levels) and plasma pharmacokinetic parameters concerning the use of the oral CRTh2 antagonist QAW039 (fevipiprant) in mild to moderate asthma patients. Information on experimental design and methods on how this data was obtained is also described. Further interpretation and discussion of this data can be found in the article "The oral CRTh2 antagonist QAW039 (fevipiprant): a phase II study in uncontrolled allergic asthma" (Erpenbeck et al., in press) [1]. PMID- 27656674 TI - Data on the mechanisms underlying succinate-induced aortic contraction. AB - We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho kinase inhibitor) reduced succinate-induced contraction in both endothelium intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger). PMID- 27656675 TI - Expression and methylation data from SLE patient and healthy control blood samples subdivided with respect to ARID3a levels. AB - Previously published studies revealed that variation in expression of the DNA binding protein ARID3a in B lymphocytes from patients with systemic lupus erythematosus (SLE) correlated with levels of disease activity ("Disease activity in systemic lupus erythematosus correlates with expression of the transcription factor AT-rich-interactive domain 3A" (J.M. Ward, K. Rose, C. Montgomery, I. Adrianto, J.A. James, J.T. Merrill et al., 2014) [1]). The data presented here compare DNA methylation patterns from SLE peripheral blood mononuclear cells obtained from samples with high numbers of ARID3a expressing B cells (ARID3a(H)) versus SLE samples with normal numbers of ARID3a(+) B cells (ARID3a(N)). The methylation data is available at the gene expression omnibus (GEO) repository, "Gene Expression Omnibus: NCBI gene expression and hybridization array data repository" (R. Edgar, M. Domrachev, A.E. Lash, 2002) [2]. Isolated B cells from SLE ARID3a(H) and ARID3a(N) B samples were also evaluated via qRT-PCR for Type I interferon (IFN) signature and pathway gene expression levels by qRT-PCR. Similarly, healthy control B cells and B cells stimulated to express ARID3a with the TLR agonist, CpG, were also compared via qRT-PCR. Primers designed to detect 6 IFNa subtype mRNAs were tested in 4 IFNa, Epstein-Barr Virus-transformed B cell lines ("Reduced interferon-alpha production by Epstein-Barr virus transformed B lymphoblastoid cell lines and lectin-stimulated lymphocytes in congenital dyserythropoietic anemia type I" (S.H. Wickramasinghe, R. Hasan, J. Smythe, 1997) [3]). The data in this article support the publication, "Human effector B lymphocytes express ARID3a and secrete interferon alpha" (J.M. Ward, M.L. Ratliff, M.G. Dozmorov, G. Wiley, J.M. Guthridge, P.M. Gaffney, J.A. James, C.F. Webb, 2016) [4]. PMID- 27656676 TI - Multivariate data validation for investigating primary HCMV infection in pregnancy. AB - We reported data concerning the Gas Chromatography-Mass Spectrometry (GC-MS) based metabolomic analysis of amniotic fluid (AF) samples obtained from pregnant women infected with Human Cytomegalovirus (HCMV). These data support the publication "Primary HCMV Infection in Pregnancy from Classic Data towards Metabolomics: an Exploratory analysis" (C. Fattuoni, F. Palmas, A. Noto, L. Barberini, M. Mussap, et al., 2016) [2]. GC-MS and Multivariate analysis allow to recognize the molecular phenotype of HCMV infected fetuses (transmitters) and that of HCMV non-infected fetuses (non-transmitters); moreover, GC-MS and multivariate analysis allow to distinguish and to compare the molecular phenotype of these two groups with a control group consisting of AF samples obtained in HCMV non-infected pregnant women. The obtained data discriminate controls from transmitters as well as from non-transmitters; no statistically significant difference was found between transmitters and non-transmitters. PMID- 27656677 TI - Data on meq gene sequence analysis of Ludhiana MDV isolates. AB - The data described are related to the article entitled "Sequence Analysis of Meq oncogene among Indian isolates of Marek's Disease Herpesvirus" M. Gupta, D. Deka, Ramneek, 2016. Seven meq genes of Ludhiana Marek's disease virus (MDV) field isolates were PCR amplified by using proof reading Platinum Pfx DNA polymerase enzyme, sequenced and then analyzed for the distinct polymorphisms and point mutations. The sequences were named as LDH 1758, LDH 2003, LDH 2483, LDH 2614, LDH 2700, LDH 2929 and LDH 3262. At this point, their deduced Meq amino acid sequences were compared with GenBank available already sequenced meq genes worldwide in their deduced amino acid form to study their identity/similarity with each other. PMID- 27656678 TI - Behavioral Problems in Juvenile Idiopathic Arthritis: A Controlled Study to Examine the Risk of Psychopathology in a Chronic Pediatric Disorder. AB - Children with juvenile idiopathic arthritis (JIA) are prone to the problems that can delay their psychosocial development; however, the existing literature has not reached a consensus on the psychological problems related to JIA. A total of 51 children and adolescents with JIA and 75 healthy controls aged 6 to 18 years were examined using the Child Behavioral Checklist (CBCL). Our results represented that 70 percent of JIA group reached "borderline clinical" range or "clinical" range in internalizing problems, while this percentage in the control group was 18 percent. In addition, our results indicated that JIA group has gotten significantly higher scores (more than twofold) in externalizing behaviors compared to control group. Furthermore, children with JIA showed higher rate of anxiety/depression, withdrawal/depression, somatic complaints, rule breaking behaviors, and aggressive behaviors as well as thought and social problems compared to control group (p < 0.001). As a conclusion, children and adolescents with JIA compared to healthy controls may show higher rate of both internalizing and externalizing problems. Furthermore, our novel findings on externalizing, social, and thought problems in JIA warrant further investigation on affected children who may be at greater risk of future psychopathologies. PMID- 27656679 TI - alphaB-crystallin Expression in Breast Cancer is Associated with Brain Metastasis. AB - BACKGROUND/OBJECTIVES: The molecular chaperone alphaB-crystallin is expressed in estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 "triple-negative" breast carcinomas and promotes brain and lung metastasis. We examined alphaB-crystallin expression in primary breast carcinomas with metastatic data to evaluate its association with prognosis and site-specific metastases. METHODS: alphaB-crystallin gene (CRYAB) expression was examined using publically available global-gene expression data (n=855 breast tumors) with first site of distant metastasis information ("855Met"). alphaB-crystallin protein expression was determined by immunohistochemistry using the clinically annotated tissue microarray (n=3987 breast tumors) from British Columbia Cancer Agency (BCCA). Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the prognostic value of alphaB-crystallin. Multivariable logistic regression analysis was used to evaluate risks of alphaB-crystallin and other markers for site of metastasis. RESULTS: In the 855Met dataset, alphaB-crystallin gene (CRYAB) expression was an independent predictor of brain as the first distant site of relapse (HR = 1.2, (95% CI 1.0-1.4), P = 0.021). In the BCCA series, alphaB-crystallin protein expression was an independent prognostic marker of poor breast cancer specific survival (HR = 1.3, (95% CI 1.1-1.6), P = 0.014). Among patients with metastases, alphaB-crystallin was the strongest independent predictor of brain metastasis (OR = 2.99 (95% CI 1.83-4.89), P < 0.0001) and the only independent predictor of brain as the first site of distant metastasis (OR = 3.15 (95% CI1.43-6.95), P = 0.005). alphaB-crystallin was also associated with worse survival (3.0 versus 4.7 months, P = 0.007). CONCLUSIONS: alphaB-crystallin is a promising biomarker to identify breast cancer patients at high risk for early relapse in the brain, independent of ER and HER2 status. PMID- 27656680 TI - PD-1 pathway-mediated regulation of islet-specific CD4+ T cell subsets in autoimmune diabetes. AB - Type 1 diabetes (T1D) is a CD4+ T cell-driven autoimmune disease resulting from the destruction of insulin-producing pancreatic beta cells. Clinical evidence and studies in non-obese diabetic (NOD) mice suggest that insulin is a major autoantigen. With this in mind, we developed insulin B10-23:IAg7 tetramer reagents to track insulin-specific CD4+ T cells in mice and interrogated the role of Programmed death-1 (PD-1) for peripheral tolerance. PD-1 is a T cell inhibitory receptor necessary to maintain tolerance and prevent T1D in NOD mice. PD-1 pathway inhibitors are increasingly used in the clinic for treating malignancies, and while many patients benefit, some develop adverse autoimmune events, including T1D. We therefore sought to understand the role of PD-1 in maintaining islet-specific tolerance in diabetes-resistant strains. B6.g7 mice express the same MHC Class II allele as NOD mice, have predominantly naive insulin-specific CD4+ T cells in the periphery, and remain diabetes-free even after PD-1 pathway blockade. Here, we examined the trafficking potential of insulin-specific CD4+ T cells in NOD and B6.g7 mice with or without anti-PD-L1 treatment, and found that PD-L1 blockade preferentially increased the number of CD44highCXCR3+ insulin-specific cells in NOD but not B6.g7 mice. Additionally, we investigated whether pancreatic islets in NOD and B6.g7 mice expressed CXCL10, a lymphocyte homing chemokine and ligand for CXCR3. Anti-PD-L1 treated and control NOD mice had detectable CXCL10 expression in the islets, while B6.g7 islets did not. These data suggest that islet tolerance may be in part attributed to the pancreatic environment and in the absence of pancreas inflammation, chemotactic cytokines may be missing. This, together with our previous data showing that PD-1 pathway blockade preferentially affects effector but not anergic self-specific T cells has implications for the use of checkpoint blockade in treating tumor patients. Our work suggests that determining tumor- and self-specific CD4+ T cell activation status (naive, effector or anergic) prior to initiation of immunotherapy would likely help to stratify individuals who would benefit from this therapy versus those who might have adverse effects or incomplete tumor control. PMID- 27656682 TI - A sliding-bulge structure at the Dicer processing site of pre-miRNAs regulates alternative Dicer processing to generate 5'-isomiRs. AB - 5'-isomiRs expand the repertoire of miRNA targets. However, how they are generated is not well understood. Previously, we showed that for some miRNAs in mammalian cells, Drosha cleaves at multiple sites to generate multiple pre-miRNAs that give rise to multiple 5'-isomiRs. Here, we showed that for some other miRNAs, 5'-isomiRs are generated by alternative Dicer processing. In addition, we showed that in miR-203, alternative Dicer processing is regulated by a conserved sliding-bulge structure at the Dicer processing site, which allows the pre-miRNA molecule to fold into two different structures that are processed differently by Dicer. So far no RNA motif that slides to change conformation and alter a protein RNA interaction has been reported. Thus, our study revealed a novel RNA motif that regulates 5'-isomiR generation in some miRNAs. It might also contribute to regulating protein-RNA interactions in other biological processes, since it takes only one point mutation to generate the sliding bulge, and there are a large number of different RNAs in the cell. PMID- 27656683 TI - Nitrogen transfer from Lupinus albus L., Trifolium incarnatum L. and Vicia sativa L. contribute differently to rapeseed (Brassica napus L.) nitrogen nutrition. AB - Nitrogen (N) transfer is well documented in legume-cereal intercropping but this is less often reported for legume-Brassica intercrops even though Brassica crops require higher levels of N fertilizers. The present study was carried out to quantify N transfer from legumes (Lupinus albus L., Trifolium incarnatum L. or Vicia sativa L.) to rapeseed (Brassica napus L.) using the split-root (15)N labelling method. After three months we observed that legumes did not alter the growth of rapeseed. Vetch showed the lowest growth and demonstrated low (15)N shoot to root translocation and no significant N transfer to rapeseed. In contrast, significant (15)N enrichment was found in lupine and clover and (15)N was transferred to the associated rapeseed plants (around 6 and 4 mg N plant(-1), respectively), which contributed 2 to 3% of the rapeseed total N. Additionally, the data revealed that N2 fixation dominated the N nutrition in lupine despite the high N level provided in the donor compartment, suggesting a greater niche segregation between companion plants. Based on the results of this study we suggest that intercropping can be a relevant contributor to rapeseed N nutrition. Among the three legumes tested, clover and lupine seemed to be the best intercropping candidates. PMID- 27656681 TI - Lentiviral-mediated phenotypic correction of cystic fibrosis pigs. AB - Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in CF transmembrane conductance regulator (CFTR), resulting in defective anion transport. Regardless of the disease-causing mutation, gene therapy is a strategy to restore anion transport to airway epithelia. Indeed, viral vector-delivered CFTR can complement the anion channel defect. In this proof-of-principle study, functional in vivo CFTR channel activity was restored in the airways of CF pigs using a feline immunodeficiency virus-based (FIV-based) lentiviral vector pseudotyped with the GP64 envelope. Three newborn CF pigs received aerosolized FIV-CFTR to the nose and lung. Two weeks after viral vector delivery, epithelial tissues were analyzed for functional correction. In freshly excised tracheal and bronchus tissues and cultured ethmoid sinus cells, we observed a significant increase in transepithelial cAMP-stimulated current, evidence of functional CFTR. In addition, we observed increases in tracheal airway surface liquid pH and bacterial killing in CFTR vector-treated animals. Together, these data provide the first evidence to our knowledge that lentiviral delivery of CFTR can partially correct the anion channel defect in a large-animal CF model and validate a translational strategy to treat or prevent CF lung disease. PMID- 27656684 TI - Purification of the subcellular compartment in which exogenous antigens undergo endoplasmic reticulum-associated degradation from dendritic cells. AB - Dendritic cells (DCs) are capable of processing and presenting exogenous antigens using MHC class I molecules. This pathway is called antigen cross-presentation and plays an important role in the stimulation of naive CD8(+) T cells for infectious and tumor immunity. Our previous studies in DC2.4 cells and bone marrow-derived DCs revealed that exogenously added ovalbumin (OVA) is processed through endoplasmic reticulum (ER)-associated degradation (ERAD) for cross presentation. In this study, we aimed to further confirm these results by purification of the subcellular compartment in which exogenous antigens undergo ERAD from homogenates of DC2.4 cells pretreated with biotinylated OVA (bOVA). bOVA-containing vesicles were purified using streptavidin (SA)-magnetic beads from cell homogenates and were found to contain ER chaperones and ERAD components together with proteins for antigen presentation. In purified microsomes, bOVA was retained in membranous fractions and degraded by the ubiquitin proteasome system in presence reticulocyte lysates and ATP. These results strongly suggested that DCs processed and degraded exogenous antigens through ERAD for cross-presentation in this purified subcellular compartment. PMID- 27656685 TI - Fluctuations in phenolic content, ascorbic acid and total carotenoids and antioxidant activity of fruit beverages during storage. AB - Stability of the total phenolic content, ascorbic acid, total carotenoids and antioxidant activity in eight fruit beverages was analyzed. The influence of storage temperature (4, 8 and 11 degrees C) during the product shelf-life (20 days) was evaluated. Pomegranate Juice presented the highest values for antioxidant activity by DPPH* assay (552.93 +/- 6.00 GAE MUg mL(-1)), total carotenoids (3.18 +/- 0.11 betaCE MUg mL(-1)), and total phenolic content (3967.07 +/- 2.47 GAE MUg mL(-1)); while Splash Blend recorded the highest levels of ascorbic acid (607.39 +/- 2.13 AAE MUg mL(-1)). The antioxidant capacity was stable at 4 and 8 degrees C for the first 8 days of storage; while carotenoids and ascorbic acid were slightly degraded through the storage time, possibly due to oxidation and/or reactions with other compounds. The results suggest that the observed variation during testing could be related to storage conditions of the final product. PMID- 27656686 TI - RON kinase isoforms demonstrate variable cell motility in normal cells. AB - INTRODUCTION: Aberrant RON (Recepteur d'Origine Nantais) tyrosine kinase activation causes the epithelial cell to evade normal growth pathways, resulting in unregulated cell proliferation, increased cell motility and decreased apoptosis. Wildtype (wt) RON has been shown to play a role in metastasis of epithelial malignancies. It presents an important potential therapeutic target for colorectal, breast, gastric and pancreatic cancer. Little is known about functional differences amongst RON isoforms RON155, RON160 and RON165. The purpose of this study was to determine the effect of various RON kinase isoforms on cell motility. METHODS: Cell lines with stable expression of wtRON were generated by inserting the coding region of RON in pTagRFP (tagged red fluorescence protein plasmid). The expression constructs of RON variants (RON155, RON160 and RON165) were generated by creating a mutagenesis-based wtRON-pTag RFP plasmid and stably transfected into HEK 293 cells. The wound closure scratch assay was used to investigate the effect on cell migratory capacity of wild type RON and its variants. RESULTS: RON transfected cells demonstrated increased cell motility compared to HEK293 control cells. RON165 cell motility was significantly increased compared to RON160 (mean percentage of wound covered 37.37% vs. 32.40%; p = 0.03). CONCLUSIONS: RON tyrosine kinase isoforms have variable cell motility. This may reflect a difference in the behavior of malignant epithelial cells and their capacity for metastasis. PMID- 27656687 TI - Converting Light Energy to Chemical Energy: A New Catalytic Approach for Sustainable Environmental Remediation. AB - We report a synthetic approach to form cubic Cu2O/Pd composite structures and demonstrate their use as photocatalytic materials for tandem catalysis. Pd nanoparticles were deposited onto Cu2O cubes, and their tandem catalytic reactivity was studied via the reductive dehalogenation of polychlorinated biphenyls. The Pd content of the materials was gradually increased to examine its influence on particle morphology and catalytic performance. Materials were prepared at different Pd amounts and demonstrated a range of tandem catalytic reactivity. H2 was generated via photocatalytic proton reduction initiated by Cu2O, followed by Pd-catalyzed dehalogenation using in situ generated H2. The results indicate that material morphology and composition and substrate steric effects play important roles in controlling the overall reaction rate. Additionally, analysis of the postreacted materials revealed that a small number of the cubes had become hollow during the photodechlorination reaction. Such findings offer important insights regarding photocatalytic active sites and mechanisms, providing a pathway toward converting light-based energy to chemical energy for sustainable catalytic reactions not typically driven via light. PMID- 27656688 TI - Silver Ions Direct Twin-Plane Formation during the Overgrowth of Single-Crystal Gold Nanoparticles. AB - It is commonly agreed that the crystalline structure of seeds dictates the crystallinity of final nanoparticles in a seeded-growth process. Although the formation of monocrystalline particles does require the use of single-crystal seeds, twin planes may stem from either single- or polycrystalline seeds. However, experimental control over twin-plane formation remains difficult to achieve synthetically. Here, we show that a careful interplay between kinetics and selective surface passivation offers a unique handle over the emergence of twin planes (in decahedra and triangles) during the growth over single crystalline gold nanoparticles of quasi-spherical shape. Twinning can be suppressed under conditions of slow kinetics in the presence of silver ions, yielding single-crystalline particles with high-index facets. PMID- 27656689 TI - Gold Nanoantenna-Mediated Photothermal Drug Delivery from Thermosensitive Liposomes in Breast Cancer. AB - In this work, we demonstrate controlled drug delivery from low-temperature sensitive liposomes (LTSLs) mediated by photothermal heating from multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. The unique geometry of MGNs enables the generation of mild hyperthermia (~42 degrees C) by converting near-infrared light to heat and effectively delivering doxorubicin (DOX) from the LTSLs in breast cancer cells. We confirmed the cellular uptake of MGNs by using both fluorescence confocal Z-stack imaging and transmission electron microscopy (TEM) imaging. We performed a cellular viability assay and live/dead cell fluorescence imaging of the combined therapeutic effects of MGNs with DOX-loaded LTSLs (DOX-LTSLs) and compared them with free DOX and DOX loaded non-temperature-sensitive liposomes (DOX-NTSLs). Imaging of fluorescent live/dead cell indicators and MTT assay outcomes both demonstrated significant decreases in cellular viability when cells were treated with the combination therapy. Because of the high phase-transition temperature of NTSLs, no drug delivery was observed from the DOX-NTSLs. Notably, even at a low DOX concentration of 0.5 MUg/mL, the combination treatment resulted in a higher (33%) cell death relative to free DOX (17% cell death). The results of our work demonstrate that the synergistic therapeutic effect of photothermal hyperthermia of MGNs with drug delivery from the LTSLs can successfully eradicate aggressive breast cancer cells with higher efficacy than free DOX by providing a controlled light-activated approach and minimizing off-target toxicity. PMID- 27656691 TI - Interfacial Activity of Gold Nanoparticles Coated with a Polymeric Patchy Shell and the Role of Spreading Agents. AB - Gold patchy nanoparticles (PPs) were prepared under surfactant-free conditions by functionalization with a binary ligand mixture of polystyrene and poly(ethylene glycol) (PEG) as hydrophobic and hydrophilic ligands, respectively. The interfacial activity of PPs was compared to that of homogeneous hydrophilic nanoparticles (HPs), fully functionalized with PEG, by means of pendant drop tensiometry at water/air and water/decane interfaces. We compared interfacial activities in three different spreading agents: water, water/chloroform, and pure chloroform. We found that the interfacial activity of PPs was close to zero (~2 mN/m) when the spreading agent was water and increased to ~14 mN/m when the spreading agent was water/chloroform. When the nanoparticles were deposited with pure chloroform, the interfacial activity reached up to 60 mN/m by compression. In all cases, PPs exhibited higher interfacial activity than HPs, which were not interfacially active, regardless of the spreading agent. The interfacial activity at the water/decane interface was found to be significantly lower than that at the water/air interface because PPs aggregate in decane. Interfacial dilatational rheology showed that PPs form a stronger elastic shell at the pendant drop interface, compared to HPs. The significantly high interfacial activity obtained with PPs in this study highlights the importance of the polymeric patchy shell and the spreading agent. PMID- 27656690 TI - Physicochemical and Antibacterial Characterization of a Novel Fluorapatite Coating. AB - Peri-implantitis remains the major impediment to the long-term use of dental implants. With increasing concern over the growth in antibiotic resistance, there is considerable interest in the preparation of antimicrobial dental implant coatings that also induce osseointegration. One such potential coating material is fluorapatite (FA). The aim of this study was to relate the antibacterial effectiveness of FA coatings against pathogens implicated in peri-implantitis to the physicochemical properties of the coating. Ordered and disordered FA coatings were produced on the under and upper surfaces of stainless steel (SS) discs, respectively, using a hydrothermal method. Surface charge, surface roughness, wettability, and fluoride release were measured for each coating. Surface chemistry was assessed using X-ray photoelectron spectroscopy and FA crystallinity using X-ray diffraction. Antibacterial activity against periodontopathogens was assessed in vitro using viable counts, confocal microscopy, and scanning electron microscopy (SEM). SEM showed that the hydrothermal method produced FA coatings that were predominately aligned perpendicular to the SS substrate or disordered FA coatings consisting of randomly aligned rodlike crystals. Both FA coatings significantly reduced the growth of all examined bacterial strains in comparison to the control. The FA coatings, especially the disordered ones, presented significantly lower charge, greater roughness, and higher area when compared to the control, enhancing bacteria-material interactions and therefore bacterial deactivation by fluoride ions. The ordered FA layer reduced not only bacterial viability but adhesion too. The ordered FA crystals produced as a potential novel implant coating showed significant antibacterial activity against bacteria implicated in peri implantitis, which could be explained by a detailed understanding of their physicochemical properties. PMID- 27656692 TI - Alarm Odor Compounds of the Brown Marmorated Stink Bug Exhibit Antibacterial Activity. AB - Some insects release scented compounds as a defense against predators that also exhibit antimicrobial activity. Trans-2-octenal and trans-2-decenal are the major alarm aldehydes responsible for the scent of Halyomorpha halys, the brown marmorated stink bug. Previous research has shown these aldehydes are antifungal and produce an antipredatory effect, but have never been tested for antibacterial activity. We hypothesized that these compounds functioned similarly to the analogous multifunctional action of earwig compounds, so we tested whether these aldehydes could inhibit the growth of bacteria. Disk diffusion assays indicated that these aldehydes significantly inhibited the growth of Methicillin-resistant Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, in vitro. Moreover, mealworm beetles (Tenebrio molitor) coated in stink bug aldehydes showed a substantial reduction in bacterial colonization compared to vehicle treated insects. These results suggest that brown marmorated stinkbug aldehydes are indeed antibacterial agents and serve a multifunctional role for this insect. Therefore, stinkbug aldehydes may have potential for use as chemical antimicrobials. PMID- 27656707 TI - Platelet granules - secretory and secretive. AB - The article reviews three recent publications addressing physiological and pathological aspects of platelet granules and release as well as limitations of recent screening tests for diagnosis of non-syndromic inherited delta-storage pool disease (1-3). PMID- 27656709 TI - Human recombinant alkaline phosphatase inhibits ex vivo platelet activation in humans. AB - Sepsis-associated acute kidney injury (AKI) is associated with high morbidity and mortality. Excessive platelet activation contributes to AKI through the formation of microthrombi and amplification of systemic inflammation. Two phase II trials demonstrated that bovine-intestinal alkaline phosphatase (AP) improved renal function in critically ill patients with sepsis-associated AKI. In this study, we characterised the platelet-inhibiting effects of a human recombinant AP. Whole blood and platelet-rich plasma (PRP) of healthy volunteers (n=6) was pre-treated ex vivo with recAP, whereafter platelet reactivity to ADP, collagen-related peptide (CRP-XL) and Pam3CSK4 was determined by flow cytometry. RecAP (40 U/ml) reduced the platelet reactivity to ADP (inhibition with a median of 47 %, interquartile range 43-49 %; p<0.001) and tended to reduce platelet reactivity to CRP-XL (9 %, 2-25 %; p=0.08) in whole blood. The platelet-inhibiting effects of recAP were more pronounced in PRP both for ADP- (64 %, 54-68 %; p=0.002) and CRP XL-stimulated samples (60 %, 46-71 %; p=0.002). RecAP rapidly converted ADP into adenosine, whereas antagonism of the A2A adenosine receptor partially reversed the platelet inhibitory effects of recAP. Platelets of septic shock patients (n=5) showed a 31% (22-34%; p=0.03) more pronounced reactivity compared to healthy volunteers, and this was completely reversed by recAP treatment. In conclusion, we demonstrate that recAP inhibits ex vivo human platelet activation through dephosphorylation of ADP and formation of adenosine as its turnover product. RecAP is able to reverse the platelet hyperreactivity present in septic shock patients. These effects may contribute to the beneficial effects of recAP as a new therapeutic candidate for sepsis-associated AKI. PMID- 27656708 TI - Genome-wide association reveals that common genetic variation in the kallikrein kinin system is associated with serum L-arginine levels. AB - L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians. We show that common genetic variations at the KLKB1 and F12 loci are strongly associated with serum L-arginine levels. The G allele of single nucleotide polymorphism (SNP) rs71640036 (T/G) in KLKB1 is associated with lower serum L-arginine concentrations (10 umol/l per allele copy, p=1*10-24), while allele T of rs2545801 (T/C) near the F12 gene is associated with lower serum L-arginine levels (7 umol/l per allele copy, p=7*10-12). Together these two loci explain 7 % of the total variance in serum L-arginine concentrations. The associations at both loci were replicated in independent cohorts with plasma L-arginine measurements (p<0.004). The two sentinel SNPs are in nearly complete LD with the nonsynonymous SNP rs3733402 at KLKB1 and the 5'-UTR SNP rs1801020 at F12, respectively. SNPs at both loci are associated with blood pressure. Our findings provide new insight into the genetic regulation of L-arginine and its potential relationship with cardiovascular risk. PMID- 27656710 TI - A stromal cell population in the large intestine identified by tissue factor expression that is lost during colorectal cancer progression. AB - Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/VIIa, and TF expression has been found in tumour cells of colorectal tumours. However, TF expression in the CRC tumour stroma or its relationship to patient outcome has not yet been studied. To address this question we developed and validated a specific anti-TF antibody using standardised methods within the Human Protein Atlas project. We used this antibody to investigate TF expression in normal colorectal tissue and CRC using immunofluorescence and immunohistochemistry in two patient cohorts. TF was strongly expressed in a cell population immediately adjacent to the colorectal epithelium. These TF-positive cells were ACTA2-negative but weakly vimentin positive, defining a specific population of pericryptal sheath cells. In colorectal tumours, TF-positive sheath cells were progressively lost after the adenoma-to-carcinoma transition, demonstrating downregulation of this source of TF in CRC. Furthermore, loss of sheath cell TF was significantly associated with poor overall and disease-specific survival in rectal but not colon cancers. In conclusion, we demonstrate that TF is a marker of a specific cell population in the large intestine, which is lost during CRC progression. Our results highlight the role of the tumour stroma in this cancer type and suggest TF to be a potential prognostic biomarker in rectal cancers through the identification of pericryptal sheath cells. PMID- 27656711 TI - Global Anticoagulant Registry in the Field - Venous Thromboembolism (GARFIELD VTE). Rationale and design. AB - Venous thromboembolism (VTE) is a common disorder associated with significant rates of morbidity and mortality. VTE management aims to reduce mortality, the risks of recurrence, and long-term complications. VTE treatment is evolving with the introduction of non-vitamin K antagonist anticoagulants (NOACs). The Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE) is a prospective, multicentre, observational study that will enrol 10,000 patients treated for acute VTE from ~500 sites in 28 countries. Identified sites reflect the diversity of care settings, including hospital and outpatient settings. Patients will be managed according to local practices and followed for at least three years. The primary objective is to determine the extent to which VTE treatment varies in the real-world setting and to assess the impact of such variability on clinical and economic outcomes. Evolving patterns of care will be captured using two sequential cohorts. The GARFIELD-VTE registry will provide insights into the evolving global treatment patterns for VTE, both deep-vein thrombosis and pulmonary embolism. By enrolling patients from diverse care settings, the registry will provide information on adherence to national and international guidelines, identify good practice as well as treatment deficiencies, and relate patient outcomes to clinical management. The incidence of death, recurrent VTE, bleeding, post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension will be documented. By capturing information during and after anticoagulation treatment, the registry will not only define aspects of the natural history of VTE, but also its economic and societal impact at a regional and global level. PMID- 27656712 TI - Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia. AB - HIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum ("fondaparinux cross-reactivity"). Ironically, despite existence of fondaparinux associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct diagnosis. PMID- 27656714 TI - Miranda's story: molecules, populations and the mortal organism. AB - [[ageingbiologydeathGilles DeleuzeMichel FoucaultMartin Heidegger]]Biomedicine is today transforming the human condition, but how such transformation is to be understood is a matter of debate. I seek to contribute to the debate by focusing on recent developments within a relatively novel subfield of gerontology which is engaged in the bio-molecular and bio-demographic characterization of the processes associated with the development of the organism from birth to death. I argue that these developments aid understanding of the conceptual difficulties confronting neo-Darwinian biological thought and poststructuralist social theory as one decentres the organism and the other the subject. PMID- 27656713 TI - Effect of Metformin on Renal Function After Primary Percutaneous Coronary Intervention in Patients Without Diabetes Presenting with ST-elevation Myocardial Infarction: Data from the GIPS-III Trial. AB - PURPOSE: The association between metformin use and renal function needs further to be elucidated since data are insufficient whether metformin affects renal function in higher risk populations such as after ST-elevation myocardial infarction (STEMI). METHODS: We studied 379 patients included in the GIPS-III trial in which patients without diabetes or renal dysfunction, who underwent primary percutaneous coronary interventions (PCI) for STEMI, were randomized to metformin 500 mg or placebo twice daily for four months. At baseline and at seven scheduled visits up to four months after PCI, estimated glomerular filtration rate (eGFR) was determined (2582 values). Contrast-induced acute kidney injury (CI-AKI) was defined as an increase in serum creatinine of >=0.3 mg/dl or 25 % rise within 48 h after PCI. RESULTS: At all visits, the mean eGFR was similar in patients randomized to metformin or placebo. Over the four month period, mixed effect repeated-measures model analysis showed a least-squares mean +/- standard error change in eGFR of -5.9+/-0.8 ml/min/1.73 m2 in the metformin group and -7.1 +/-0.8 ml/min/1.73 m2 in the control group (P=0.27 for overall interaction). The incidence of CI-AKI was 14.8 %; 29 (15.2 %) patients in the metformin group versus 27 (14.4 %) controls (P=0.89). After adjustment for covariates, metformin treatment was not associated with CI-AKI (odds ratio: 0.96, 95%CI 0.52-1.75, P=0.88). CONCLUSION: We conclude that initiation of metformin shortly after primary PCI has no adverse effect on renal function in patients without diabetes or prior renal impairment, further providing evidence of the safety of metformin use after myocardial infarction and subsequent contrast exposure. PMID- 27656715 TI - A systematic archival inquiry on Juan Huarte de San Juan (1529-88). AB - [[Examen de Ingenios historyJuan HuarteTrial of Men's Wits psychiatrypsychology ]] Juan Huarte de San Juan (1529-88) was a physician of the Spanish Renaissance. He wrote the Examen de Ingenios para las Ciencias, translated as The Trial of Men's Wits (1989[1575-94]), a book that has been acknowledged as a precursor of educational psychology, organizational psychology, behaviorism, neuropsychology and psychiatry. Huarte suggested that before beginning a course of study, students' intellectual capabilities (i.e. ingenio) should be matched up with the professional studies that best suit their aptitudes. His book had a great impact in Europe from the late 16th century to the mid-18th century. The influence of the Trial spread throughout many areas including philosophy, politics, linguistics and literature. Although there has been a growing interest in Huarte's work in recent years, biographical studies have been rare; as a result, the information about Huarte's life is currently incomplete, scattered and sometimes inaccurate. This study presents a systematic archival research on Spanish original sources. We present a reconstruction of Huarte's life-story based on 32 original documents (1549-c.1650), some of them first discovered during the present survey. Documents are described according to the General International Standard of Archival Description, ISAD(G). The documents uncovered allow for a reappraisal of Huarte's biography. PMID- 27656716 TI - 'Bildung' in German human sciences: the discursive transformation of a concept . AB - [[Bildung disciplinesdiscourse analysisfield analysisGeisteswissenschaften Germanyhumanitiessocial sciences and humanities studies ]] This article analyses the transformation of the notion of Bildung that is constructed in the German human sciences. From a perspective of field theory and discourse analysis, the article reveals how the notion evolves and stabilizes during a first stage (1810 60), how it comes under pressure because of the contextual changes in a second stage (1860-1960) and how the tension increases before it is resolved by a fundamental change of the traditional notion of Bildung in a third stage (1960 99). PMID- 27656717 TI - Between structure and agency: assassination, social forces, and the production of the criminal subject. AB - [[agencyassassinationLeon Czolgoszsocial forcesstructure ]] Assassins are often regarded as ahistorical figures of evil. In this article, I contest this view by analysing the assassination of President William McKinley by Leon Czolgosz in 1901. There are two purposes to this article. The first is to situate McKinley's assassination within the history and development of the social sciences, principally sociology, rather than assume that the assassin is a trans-historical representation of willful irresponsibility. The second is to describe and critique the discourse that made Czolgosz into a rational agent once he entered history as an assassin. PMID- 27656718 TI - The interplay of courage and reason in moral action. AB - [[courageJurgen HabermasChristoph MenkemoralityPlatoreasonPeter Sloterdijk ]] This article argues that both courage and reason are necessary aspects of moral action. It begins by examining Plato's changing conceptions of these two virtues, and, in particular, the settled view he arrives at in The Statesman. Sloterdijk's recent attempt in his book advocating rage to appropriate this dialogue in order to criticize Habermas is then considered. I suggest, by interpreting various claims by these two authors, that neither understands that both reason and courage have essential roles in moral action. Additional support for this conclusion is found, not just in Plato's late work, but in a 'third generation' reworking of critical theory recently developed by Menke. PMID- 27656719 TI - In defence of language-interpretive social science: on the critiques of Peter Winch's conception of understanding. AB - [[critical theoryinterpretationsocial scienceunderstandingPeter Winch ]] In his highly influential book (The Idea of a Social Science and its Relation to Philosophy, first published in 1958), Peter Winch introduces an alternative concept of interpretive social science, in which the focus is shifted from the actors' subjective motives to the common elements found in every understandable action: language-games and rule-following. This Wittgensteinian, linguistic version of interpretive social science has had its vast array of critics throughout the years: according to some of them, it neglects the practical side of sociology; while others claim that it fails properly to answer the questions raised by the translation from one language-game to another, or that it renders critical social theory impossible. In my article, I try to reflect critically upon these critiques themselves, showing that the Winchian theory does not overlook the practice in understanding the different forms of life; that with slight modifications it is able to cope with the problem of translation, and that it does not aspire to be the critical theory that many of its critics would like it to be. PMID- 27656720 TI - Histories and freedom of the present: Foucault and Skinner. AB - [critiquefreedomlanguagemethod ]] This article compares the ways in which Michel Foucault's and Quentin Skinner's historical analyses seek to unsettle the limits on present forms of freedom. We do so by comparing their ways of analysing discourse, rationality and agency. The two authors differ significantly in the ways they deal with these three phenomena. The most significant difference lies in their ways of addressing agency and its relationship to power. Notwithstanding these differences, the historical analyses of both authors seek to problematize the ways in which past thoughts and practices limit contemporary forms of freedom. While Foucault seems to go furthest in this endeavour, a comparison may enrich both lines of historical analyses. PMID- 27656721 TI - Eurocentrism beyond the 'universalism vs. particularism' dilemma: Habermas and Derrida's joint plea for a new Europe. AB - [[cosmopolitanismexpansionismidealismparticularismUNuniversalism ]] Is it Eurocentric on the part of western philosophers (Habermas, Derrida) or of researchers in human sciences to set out from a specific locality (Europe) to formulate ethico-political ideals with universal aspirations? In this article, I critique the 'universalism vs. particularism' framework within which the charge of Eurocentrism is deployed and I redefine the notion of Eurocentrism outside the drastic choice between universalism and particularism and in light of an 'ec centric' reflection on the entanglement of the 'We' and the 'others'. I illustrate my position by discussing the Habermasian-Derridean plea for the determination of new European political responsibilities beyond any Eurocentrism. I grant that the two philosophers go indeed beyond Eurocentrism as the latter is usually understood, i.e. along the axis 'universal-particular'. Yet, without minimizing their political contribution, I detect subtler Eurocentrisms that pervade several assumptions of Habermas's and Derrida's collaborative efforts. I argue that a hasty enlisting of possibilities for a politically and morally pertinent European intervention in world affairs fails to account for other, more necessary steps in the direction of reforming the western consciousness and of going beyond less easily discernible Eurocentrisms such as those theorized within the proposed, reformulated notion. PMID- 27656722 TI - Liberty, necessity and the foundations of Hume's 'science of man'. AB - [[analysis-synthesisDavid Humeideology of modern sciencescience of mantheodicy ]] In this article I suggest that section VIII of Hume's Enquiry Concerning Human Understanding could be read as a contribution to the foundational issues of a characteristic 18th-century enterprise, namely the 'science of man'. More specifically, it can be read as a summary of his attempt to place this science on an experimental footing, with an awareness of the lessons he has drawn in the previous sections of the Enquiry. This interpretation fits with an overall reading of the work as responding to the epistemological problems that arise in the context of then-contemporary ways of knowledge production. As I argue, this section is relevant for the methodology of a science of human nature. The main problems it addresses are the following. What kind of knowledge can we hope for about human beings, and how should we pursue it? What are the meaningful questions that can be asked, and what is beyond the reach of this kind of inquiry? Answering these questions sets the scope and limits of this science. PMID- 27656723 TI - 'On what condition is the equation organism-society valid?' Cell theory and organicist sociology in the works of Alfred Espinas (1870s-80s). AB - [[cellular theorydivision of labourindividualorganicismorganismsocietywhole-parts relations ]] In 1877, the young Alfred Espinas defended a philosophical study, 'doctorat es lettres', at the Sorbonne University, entitled Des Societes animales. This was to become one of the principal sources of French organicist sociology. The paradox, however, is that this work seems to be fundamentally a study of natural science. Espinas tried to justify his position theoretically through two types of reciprocally exclusive and uncomplementary arguments. The first one consists in showing that only certain kinds of animal groupings belong legitimately, if not academically, to sociology. The second one has a greater audacious and uncontrollable dimension. It consists in asserting that all pluricellular organisms are true societies. In this article we first focus on the role played by cellular theory in such a 'sociologization' of biology, concerning the extension of sociology. Second, we examine the importance of such confusion within the fields of extension, in aiming to explain the conceptual transfers between social sciences and life sciences, in the second half of the 19th century. PMID- 27656724 TI - Sociological theory and Jungian psychology. AB - [[disenchantmentCarl JungpsychoanalysissociologyMax Weber ] In this article I seek to relate the psychology of Carl Jung to sociological theory, specifically Weber. I first present an outline of Jungian psychology. I then seek to relate this as psychology to Weber's interpretivism. I point to basic methodological compatibilities within a Kantian frame, from which emerge central concerns with the factors limiting rationality. These generate the conceptual frameworks for parallel enquiries into the development and fate of rationality in cultural history. Religion is a major theme here: contrasts of eastern and western religion; the rise of prophetic religion and the disenchantment of modernity. Weber's categories 'ascetic' and 'mystic' seem applicable to his own and Jung's approaches and indeed temperaments, while a shared ironic view of rationality leads to similar visions of the disenchanted modern world. I conclude that Jung is sociologically coherent, but in an entirely different sense from Freud: rather than a constellation of family, socialization, ideology, social continuity, there is an analysis of cultural history against a background of adult normal psychology. I conclude that sociology should acknowledge Jung, but not in terms of over-arching theory. Rather Jungian insights might be used to orient new enquiries, and for reflexive analysis of sociology's methodological debates. PMID- 27656725 TI - 'A most interesting chapter in the history of science' intellectual responses to Alfred Kinsey's Sexual Behavior in the Human Male. AB - [[history of scienceintellectual historyinterdisciplinary researchAlfred Kinseysexuality ]] There were three broad categories of academic responses to Alfred Kinsey's Sexual Behavior in the Human Male (Kinsey, Pomeroy and Martin, 1948): method; findings; and broader reflections on the book's place in American social life and democracy. This article focuses primarily on archival academic responses to Kinsey's work that appeared in the year following the book's publication. Many academics agreed that some aspects of Kinsey's method were flawed and that his interpretations sometimes overreached his raw data. Nonetheless, they also agreed that no one else had gathered such a diverse sampling of interviewees whose behaviors Kinsey could use to create new interpretive models of human sexuality. As Kinsey's research was deliberately interdisciplinary, his research and statistical methodologies began to catch on in the human sciences and to encourage academics and intellectuals to rethink their human science practices. As academics reflected on the volume's larger meaning in American life, several of them thought it exemplified the worst American values (emphases on money and size) while others saw the very existence of the Male volume as an excellent example of the ability of free citizens to pursue and to publish research on any topic. While members of the American intelligentsia championed the Male volume and its findings as democratic, the reception of Sexual Behavior in the Human Female (Kinsey, Pomeroy, Martin and Gebhard, 1953), published at an intense moment of the cold war, was viewed as a communist threat to American security for revealing the sexual secrets of the public. PMID- 27656726 TI - Children having children? Religion, psychology and the birth of the teenage pregnancy problem. AB - [[Britainchildren having childrenpsychologysubjectivityteenage pregnancyunwed mothers ]] This article presents a genealogical examination of the emergence of governmental concern with 'children having children', focusing on the work of the London County Council and local voluntary organizations in the 1950s and 1960s. The article explores the moral-Christian discourse shaping governmental work with 'unwed mothers' and identifies the discursive shifts associated with the ascent of the problematization of 'teenage motherhood'. It is argued that within the moral-Christian discourse, a woman's subjectivity was delineated primarily according to her 'character' not her age or her 'maturity'. Furthermore, the prospect that a young unwed mother will raise her child was viewed positively as it was seen to contribute to the desired transformation of her character. The shift to a concern with 'children having children' was linked with a rise in the influence of psychological discourse on government work. Two psychological notions were particularly important: the proposition that teenagers are emotionally immature and the assertion that inadequate mothering has a lasting effect on the health of a child. The article concludes that unless contemporary scientific claims regarding young people's psychological and physiological maturity are challenged, the 'problem' of teenage parenthood will persist in the years to come. PMID- 27656727 TI - Error in Text. Published Erratum. PMID- 27656755 TI - Micro X-ray Fluorescence Imaging in a Tabletop Full Field-X-ray Fluorescence Instrument and in a Full Field-Particle Induced X-ray Emission End Station. AB - A full field-X-ray camera (FF-XRC) was developed for performing the simultaneous mapping of chemical elements with a high lateral resolution. The device is based on a conventional CCD detector coupled to a straight shaped polycapillary. Samples are illuminated at once with a broad primary beam that can consist of X rays or charged particles in two different analytical setups. The characteristic photons induced in the samples are guided by the polycapillary to the detector allowing the elemental imaging without the need for scanning. A single photon counting detection operated in a multiframe acquisition mode and a processing algorithm developed for event hitting reconstruction have enabled one to use the CCD as a high energy resolution X-ray detector. A novel software with a graphical user interface (GUI) programmed in Matlab allows full control of the device and the real-time imaging with a region-of-interest (ROI) method. At the end of the measurement, the software produces spectra for each of the pixels in the detector allowing the application of a least-squares fitting with external analytical tools. The FF-XRC is very compact and can be installed in different experimental setups. This work shows the potentialities of the instrument in both a full field micro X-ray fluorescence (FF-MXRF) tabletop device and in a full field-micro particle induced X-ray emission (FF-MPIXE) end-station operated with an external proton beam. Some examples of applications are given as well. PMID- 27656756 TI - Epitaxial Growth of Atomically Smooth Aluminum on Silicon and Its Intrinsic Optical Properties. AB - Aluminum (Al) provides an excellent material platform for plasmonic applications in the ultraviolet (UV) regime due to its low loss coefficient at UV wavelengths. To fully realize the potential of this material, it is imperative to create nanostructures with minimal defects in order to prevent light scattering and better support plasmonic resonances. In this work, we report the successful development of atomically smooth epitaxial Al films on silicon. These epitaxial Al thin films facilitate the creation of fine plasmonic nanostructures and demonstrate considerable loss reduction in the UV frequency range, in comparison to the polycrystalline Al films based on spectroscopic ellipsometry measurements. Remarkably, our measurements on the epitaxial Al film grown using the two-step method suggest that the intrinsic loss in Al is significantly lower, by up to a factor of 2 in the UV range, with respect to current widely quoted Palik's values extracted from polycrystalline films. These high-quality epitaxial Al films provide an ideal platform for UV plasmonics. In addition, the availability of intrinsic optical constants will enable more accurate theoretical predictions to guide the device design. PMID- 27656757 TI - Environmental Comparison of Biochar and Activated Carbon for Tertiary Wastewater Treatment. AB - Micropollutants in wastewater present environmental and human health challenges. Powdered activated carbon (PAC) can effectively remove organic micropollutants, but PAC production is energy intensive and expensive. Biochar adsorbents can cost less and sequester carbon; however, net benefits depend on biochar production conditions and treatment capabilities. Here, life cycle assessment was used to compare 10 environmental impacts from the production and use of wood biochar, biosolids biochar, and coal-derived PAC to remove sulfamethoxazole from wastewater. Moderate capacity wood biochar had environmental benefits in four categories (smog, global warming, respiratory effects, noncarcinogenics) linked to energy recovery and carbon sequestration, and environmental impacts worse than PAC in two categories (eutrophication, carcinogenics). Low capacity wood biochar had even larger benefits for global warming, respiratory effects, and noncarcinogenics, but exhibited worse impacts than PAC in five categories due to larger biochar dose requirements to reach the treatment objective. Biosolids biochar had the worst relative environmental performance due to energy use for biosolids drying and the need for supplemental adsorbent. Overall, moderate capacity wood biochar is an environmentally superior alternative to coal-based PAC for micropollutant removal from wastewater, and its use can offset a wastewater facility's carbon footprint. PMID- 27656758 TI - Polluting Black space. AB - Social psychologists have long demonstrated that people are stereotyped on the basis of race. Researchers have conducted extensive experimental studies on the negative stereotypes associated with Black Americans in particular. Across 4 studies, we demonstrate that the physical spaces associated with Black Americans are also subject to negative racial stereotypes. Such spaces, for example, are perceived as impoverished, crime-ridden, and dirty (Study 1). Moreover, these space-focused stereotypes can powerfully influence how connected people feel to a space (Studies 2a, 2b, and 3), how they evaluate that space (Studies 2a and 2b), and how they protect that space from harm (Study 3). Indeed, processes related to space-focused stereotypes may contribute to social problems across a range of domains-from racial disparities in wealth to the overexposure of Blacks to environmental pollution. Together, the present studies broaden the scope of traditional stereotyping research and highlight promising new directions. (PsycINFO Database Record PMID- 27656759 TI - Domino Assembly of Trifluoromethylated N,O-Heterocycles by the Reaction of Fluorinated alpha-Bromoenones with Amino Alcohols. AB - A highly efficient method for the selective synthesis of trifluoromethylated morpholines (4-oxa-1-azabicyclo[4.1.0]heptanes) and so far unknown 1,4-oxazepanes (2,8-dioxa-5-azabicyclo[5.1.0]octanes) based on a domino reaction of fluorinated alpha-bromoenones with beta-amino alcohols was elaborated. The assembly of both heterocyclic systems is initiated by an aza-Michael reaction followed by intramolecular cyclization. The conditions for total control of selectivity of the reaction were found. PMID- 27656760 TI - Heavy-Hole States in Germanium Hut Wires. AB - Hole spins have gained considerable interest in the past few years due to their potential for fast electrically controlled qubits. Here, we study holes confined in Ge hut wires, a so-far unexplored type of nanostructure. Low-temperature magnetotransport measurements reveal a large anisotropy between the in-plane and out-of-plane g-factors of up to 18. Numerical simulations verify that this large anisotropy originates from a confined wave function of heavy-hole character. A light-hole admixture of less than 1% is estimated for the states of lowest energy, leading to a surprisingly large reduction of the out-of-plane g-factors compared with those for pure heavy holes. Given this tiny light-hole contribution, the spin lifetimes are expected to be very long, even in isotopically nonpurified samples. PMID- 27656761 TI - Health Literacy in Adolescents and Young Adults: Perspectives from Australian Cancer Survivors. AB - PURPOSE: Health literacy is a critical determinant of health and an emerging public health concern. Little is known about the health literacy of adolescents and young adults (AYAs) or about the ability of young patients to communicate health needs and critically evaluate information. We used qualitative methods to investigate the three aspects of health literacy (functional, communicative, and critical) in Australian AYA cancer survivors. METHODS: Forty Australian AYA cancer survivors, aged 15-29 either at diagnosis or recruitment, participated in semistructured interviews. Participants were asked about sources of information and ability to understand information, communicate questions, and critically evaluate the validity, reliability, and relevancy of information to their situation. Self-reported adherence levels and advice for AYA-specific care was also obtained. Interviews were coded and analyzed for emergent themes using QSR NVivo 10. RESULTS: Almost all AYAs named their doctor as the primary source of information. Most AYAs reported no difficulties with understanding, communicating, or assessing relevancy of information. Conversely, few AYAs reported confidence in assessment of validity and reliability of information. The doctor-patient relationship appeared to be an influential factor in all aspects of health literacy. CONCLUSIONS: AYAs frequently reported having a good understanding and communication around health information; however, few AYAs described engaging in critical evaluations of this information. The potential impact of the doctor-patient relationship across several domains of health literacy suggests that more focus could be placed on promoting health literacy at physician, community, and societal levels, in addition to promoting individual skills. PMID- 27656763 TI - Total Synthesis of (+/-)-Kuwanol E. AB - The total synthesis of the Diels-Alder-type adducts (+/-)-kuwanol E and the heptamethyl ether derivative of (+/-)-kuwanon Y has been accomplished via a convergent strategy involving 2'-hydroxychalcone 6 or 9 and dehydroprenylstilbene 7, in nine steps. The synthesis features, as a key step, a Lewis acid-mediated biomimetic intermolecular Diels-Alder [4+2] cycloaddition for the construction of the cyclohexene skeleton with three stereogenic centers. Notably, the endo/exo diastereoselectivity of the reaction proved to be temperature-controlled. PMID- 27656762 TI - Hypogonadism alters cecal and fecal microbiota in male mice. AB - Low testosterone levels increase the risk for cardiovascular disease in men and lead to shorter life spans. Our recent study showed that androgen deprivation via castration altered fecal microbiota and exacerbated risk factors for cardiovascular disease, including obesity, impaired fasting glucose, excess hepatic triglyceride accumulation, and thigh muscle weight loss only in high-fat diet (HFD)-fed male mice. However, when mice were administered antibiotics that disrupted the gut microbiota, castration did not increase cardiovascular risks or decrease the ratio of dried feces to food intake. Here, we show that changes in cecal microbiota (e.g., an increased Firmicutes/Bacteroidetes ratio and number of Lactobacillus species) were consistent with changes in feces and that there was a decreased cecal content secondary to castration in HFD mice. Castration increased rectal body temperature and plasma adiponectin, irrespective of diet. Changes in the gut microbiome may provide novel insight into hypogonadism-induced cardiovascular diseases. PMID- 27656764 TI - A structure-based kinetic model of transcription. AB - During transcription, RNA polymerase moves downstream along the DNA template and maintains a transcription bubble. Several recent structural studies of transcription complexes with a complete transcription bubble provide new insights into how RNAP couples the nucleotide addition reaction to its directional movement. PMID- 27656765 TI - The Evolution of Pd0/PdII-Catalyzed Aromatic Fluorination. AB - Aromatic fluorides are prevalent in both agrochemical and pharmaceutical agents. However, methods for their rapid and general preparation from widely available starting materials are limited. Traditional approaches such as the Balz-Schiemann and Halex reactions require harsh conditions that limit functional group tolerance and substrate scope. The use of transition metals to affect C-F bond formation has provided some useful alternatives, but a broadly applicable method remains elusive. In contrast to the widespread use of Pd0/PdII catalysis for aryl Z bond formation (Z = C, N, O), the analogous C-F cross-coupling process was unknown until fairly recently. In large part, this is due to the challenging Ar-F reductive elimination from Pd(II) intermediates. We have discovered that certain biaryl monophosphine ligands are uniquely capable of promoting this transformation. In this Account, we describe the discovery and development of a Pd-catalyzed C-F cross-coupling process and the systematic developments that made this once hypothetical reaction possible. Key to these developments was the discovery of an unusual in situ ligand modification process in which a molecule of substrate is incorporated into the ligand scaffold and the identity of the modifying group is crucial to the outcome of the reaction. This prompted the synthesis of a variety of "premodified" ligands and the identification of one that led to an expanded substrate scope, including (hetero)aryl triflates and bromides. Contemporaneously, a new Pd(0) precatalyst was also discovered that avoids the need to reduce Pd(II) in situ, a process that was often inefficient and led to the formation of byproducts. The use of inexpensive but hygroscopic sources of fluoride necessitates a reaction setup inside of a N2-filled glovebox, limiting the practicality of the method. Thus, a preformed wax capsule was designed to isolate the catalyst and reagents from the atmosphere and permit benchtop storage and setup. This new technology thus removes the requirement to employ a glovebox for the aromatic fluorination process and other air-sensitive protocols. In every catalyst system that we have studied to date, we observed the formation of regioisomeric fluoride side products. Through deuterium labeling studies it was found that they likely arise from a deprotonation event resulting in the formation of HF and a Pd-benzyne intermediate. Through an investigation of the mechanism of this undesired pathway, a new ligand was designed that substantially reduces the formation of the aryl fluoride regioisomer and even allows room-temperature Ar-F reductive elimination from a Pd(II) intermediate. PMID- 27656766 TI - Effects of Changes in BI-RADS Density Assessment Guidelines (Fourth Versus Fifth Edition) on Breast Density Assessment: Intra- and Interreader Agreements and Density Distribution. AB - OBJECTIVE: The objective of our study was to determine intra- and interreader agreements for density assessment using the fifth edition of the BI-RADS guidelines and to compare with those for density assessment using the fourth edition of the BI-RADS guidelines. MATERIALS AND METHODS: Five radiologists assessed breast density four times in 104 mammographic examinations: twice using the fourth edition of the BI-RADS guidelines and twice using the fifth edition. The intra- and interreader agreements for density assessment based on each guideline were determined and compared. The density distribution pattern under each of the four BI-RADS density categories using each guideline was also noted and compared. RESULTS: The intrareader agreement for density assessment using the fifth-edition criteria was lower than that using the fourth-edition criteria (p = 0.0179). The overall intrareader agreement (weighted kappa) using the old criteria was 0.84 (95% CI, 0.80-0.87), and the individual intrareader agreement values in five readers ranged from 0.78 (95% CI, 0.69-0.88) to 0.92 (95% CI, 0.87 0.97). The overall intrareader agreement using the new BI-RADS criteria was 0.77 (95% CI, 0.73-0.81), and the individual intrareader agreement values in five readers ranged from 0.74 (95% CI, 0.64-0.84) to 0.99 (95% CI, 0.98-1.00). The interreader agreement values obtained using the fifth-edition criteria were also lower than those obtained using the fourth-edition criteria (p = 0.006). The overall interreader agreement using the old BI-RADS criteria was 0.65 (95% CI, 0.61-0.69), whereas the overall interreader agreement using the new BI-RADS criteria was 0.57 (95% CI, 0.53-0.61). Overall a higher number of dense assessments were given when the fifth-edition guidelines were used (p < 0.0001). CONCLUSION: Compared with the intra- and interreader agreements obtained using the fourth edition of the BI-RADS guidelines, the intra- and interreader agreements were lower using the fifth-edition guidelines. An increased number of dense assessments were given when the fifth-edition guidelines were used. PMID- 27656767 TI - Consequences of work group manpower and expertise understaffing: A multilevel approach. AB - Complaints of chronic understaffing in organizations have become common among workers as employers face increasing pressures to do more with less. Unfortunately, despite its prevalence, there is currently limited research in the literature regarding the nature of workplace understaffing and its consequences. Taking a multilevel approach, this study introduces a new multidimensional conceptualization of subjective work group understaffing, comprising of manpower and expertise understaffing, and examines both its performance and well-being consequences for individual workers (Study 1) and work groups (Study 2). Results show that the relationship between work group understaffing and individual and work group emotional exhaustion is mediated through quantitative workload and role ambiguity for both levels of analysis. Work group understaffing was also related to individual job performance, but not group performance, and this relationship was mediated by role ambiguity. Results were generally similar for the 2 dimensions of understaffing. Implications for theory and research and future research directions are discussed. (PsycINFO Database Record PMID- 27656768 TI - Ultrafast Dynamics of Photongenerated Holes at a CH3OH/TiO2 Rutile Interface. AB - Photogenerated charge carrier dynamics near molecule/TiO2 interfaces are important for the photocatalytic and photovoltaic processes. To understand this fundamental aspect, we performed a time-domain ab initio nonadiabatic molecular dynamics study of the photogenerated hole dynamics at the CH3OH/rutile TiO2(110) interface. We studied the forward and reverse hole transfer between TiO2 and CH3OH as well as the hole energy relaxation to the valence band maximum. First, we show that the hole-trapping ability of CH3OH depends strongly on the adsorption structure. Only when the CH3OH is deprotonated to form chemisorbed CH3O will ~15% of the hole be trapped by the molecule. Second, we find that strong fluctuations of the HOMO energies of the adsorbed molecules induced by electron-phonon coupling provide additional channels, which accelerate the hole energy relaxation. Third, we demonstrate that the charge transfer and energy relaxation processes depend significantly on temperature. When the temperature decreases from 100 to 30 K, the forward hole transfer and energy relaxation processes are strongly suppressed because of the reduction of phonon occupation. These results indicate that the molecule/TiO2 energy level alignment, thermal excitation of a phonon, and electron-phonon coupling are the key factors that determine the photogenerated hole dynamics. Our studies provide valuable insights into the photogenerated charge and energy transfer dynamics at molecule/semiconductor interfaces. PMID- 27656769 TI - Asthma control in adolescents 10 to 11 y after exposure to the World Trade Center disaster. AB - BACKGROUND: Little is known about asthma control in adolescents who were exposed to the World Trade Center (WTC) attacks of 11 September 2001 and diagnosed with asthma after 9/11. This report examines asthma and asthma control 10-11 y after 9/11 among exposed adolescents. METHODS: The WTC Health Registry adolescent Wave 3 survey (2011-2012) collected data on asthma diagnosed by a physician after 11 September 2001, extent of asthma control based on modified National Asthma Education and Prevention Program criteria, probable mental health conditions, and behavior problems. Parents reported healthcare needs and 9/11-exposures. Logistic regression was used to evaluate associations between asthma and level of asthma control and 9/11-exposure, mental health and behavioral problems, and unmet healthcare needs. RESULTS: Poorly/very poorly controlled asthma was significantly associated with a household income of <=$75,000 (adjusted odds ratio (AOR): 3.0; 95% confidence interval (CI): 1.1-8.8), having unmet healthcare needs (AOR: 6.2; 95% CI: 1.4-27.1), and screening positive for at least one mental health condition (AOR: 5.0; 95% CI: 1.4-17.7), but not with behavioral problems. The impact of having at least one mental health condition on the level of asthma control was substantially greater in females than in males. CONCLUSIONS: Comprehensive care of post-9/11 asthma in adolescents should include management of mental health-related comorbidities. PMID- 27656770 TI - Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case-cohort study. AB - BACKGROUND: The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the literature. METHODS: This case-cohort study included 424 mother-child pairs who participated in a prospective, multi-center study of parous women in Norway (Trondheim and Bergen) and Sweden (Uppsala). We used linear and logistic regression with 95% confidence intervals (CIs) to analyze the associations between two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) from early second trimester and indices of fetal growth. RESULTS: Among Swedish women, prenatal exposure to perfluorooctanoate (PFOA), polychlorinated biphenyl (PCB) 153 and hexachlorobenzene (HCB) were associated with higher odds for SGA birth. We found stronger associations among Swedish male offspring. In the Norwegian cohort, we found no significant associations between EDC exposure and indices of fetal growth. CONCLUSIONS: Some populations may be more vulnerable to EDCs, possibly due to differences in exposure levels, exposure sources and/or modifiable lifestyle factors. Male offspring may be more vulnerable to endocrine disruption. PMID- 27656772 TI - Effect of perinatal glucocorticoids on vascular health and disease. AB - The benefits of antenatal glucocorticoids are now firmly established in the perinatal management of threatened preterm birth. Postnatal glucocorticoid therapy, however, remains controversial in neonatal medicine, with the need to balance short-term physiological benefits against the potential for long-term adverse consequences. This review focuses on the vascular effects of prenatal and postnatal glucocorticoids, synthesizing data from both experimental animal models and human infants with the goal of better appreciation of the short and long-term effects of these commonly used drugs. Due to their widespread and varied use, improved understanding of the cellular and molecular impact of glucocorticoids is important in guiding current practice and future research. PMID- 27656771 TI - Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis. AB - BACKGROUND: We have shown previously that enteral administration of 2, 4, 6 trinitrobenzene sulfonic acid in 10-d-old C57BL/6 pups produces an acute necrotizing enterocolitis with histopathological and inflammatory changes similar to human necrotizing enterocolitis (NEC). To determine whether murine neonatal 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-mediated intestinal injury could be used as a NEC model, we compared gene expression profiles of TNBS-mediated intestinal injury and NEC. METHODS: Whole-genome microarray analysis was performed on proximal colon from control and TNBS-treated pups (n = 8/group). For comparison, we downloaded human microarray data of NEC (n = 5) and surgical control (n = 4) from a public database. Data were analyzed using the software programs Partek Genomics Suite and Ingenuity Pathway Analysis. RESULTS: We detected extensive changes in gene expression in murine TNBS-mediated intestinal injury and human NEC. Using fold-change cut-offs of +/-1.5, we identified 4,440 differentially-expressed genes (DEGs) in murine TNBS-mediated injury and 1,377 in NEC. Murine TNBS-mediated injury and NEC produced similar changes in expression of orthologous genes (r = 0.611, P < 0.001), and also activated nearly-identical biological processes and pathways. Lipopolysaccharide was top predicted upstream regulator in both the murine and human datasets. CONCLUSION: Murine neonatal TNBS mediated enterocolitis and human NEC activate nearly-identical biological processes, signaling pathways, and transcriptional networks. PMID- 27656773 TI - Cystinosin-LKG rescues cystine accumulation and decreases apoptosis rate in cystinotic proximal tubular epithelial cells. AB - BACKGROUND: Nephropathic cystinosis is a lysosomal storage disease that is caused by mutations in the CTNS gene encoding a cystine/proton symporter cystinosin and an isoform cystinosin-LKG which is generated by an alternative splicing of exon 12. We have investigated the physiological role of the cystinosin-LKG that is widely expressed in epithelial tissues. METHODS: We have analyzed the intracellular localization and the function of the cystinosin-LKG conjugated with DsRed (cystinosin-LKG-RFP) in Madin-Darby canine kidney cells (MDCK II) and in proximal tubular epithelial cells carrying a deletion of the CTNS gene (cystinotic PTEC), respectively. RESULTS: Cystinosin-LKG-RFP colocalized with markers of lysosomes, late endosomes and was also expressed on the apical surface of polarized MDCK II cells. Moreover, immune-electron microscopy images of MDCK II cells overexpressing cystinosin-LKG-RFP showed stacked lamellar membranes inside perinuclear lysosomal structures. To study the role of LKG-isoform, we have investigated cystine accumulation and apoptosis that have been described in cystinotic cells. Cystinosin-LKG decreased cystine levels by approximately 10 fold similarly to cystinosin-RFP. The levels of TNFalpha- and actinomycin D inducted apoptosis dropped in cystinotic cells expressing LKG-isoform. This effect was also similar to the main isoform. CONCLUSION: Our results suggest that cystinosin-LKG and cystinosin move similar functional activities in cells. PMID- 27656774 TI - Antifungal activity of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides: A novel type of compound afforded by azide-enolate (3+2) cycloaddition. AB - The first report of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides (7a and 7b) is described herein. Azide-enolate (3+2) cycloaddition afforded the synthesis of this novel type of compound. Antifungal activity was evaluated in vitro against four filamentous fungi (Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis) as well as nine species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 7a and 7b are promising candidates for complementary biological studies due to their good activity against Candida spp. PMID- 27656775 TI - Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIalpha inhibitors. AB - A series of imidazopyridinyl-1,3,4-oxadiazole conjugates were synthesized and investigated for their cytotoxic activity and some compounds showed promising cytotoxic activity. Compound 8q (NSC: 763639) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10MUM) on all human cancer cell lines. This compound was further evaluated at five dose levels (0.01, 0.1, 1, 10 and 100MUM) to obtain GI50 values ranging from 1.30 to 5.64MUM. Flow cytometric analysis revealed that compound 8q arrests the A549 cells in sub G1 phase followed by induction of apoptosis which was further confirmed by Annexin-V-FITC, Hoechst nuclear staining, caspase 3 activation, measurement of mitochondrial membrane potential and ROS generation. Topo II mediated DNA relaxation assay results showed that conjugate 8q could significantly inhibit the activity of topo II. Moreover, molecular docking studies also indicated binding to the topoisomerase enzyme (PDBID 1ZXN). PMID- 27656776 TI - Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations. AB - The synthesis and reactivity of a series of mononuclear nonheme iron complexes that carry out intramolecular aromatic C-F hydroxylation reactions is reported. The key intermediate prior to C-F hydroxylation, [FeIV(O)(N4Py2Ar1)](BF4)2 (1-O, Ar1 = -2,6-difluorophenyl), was characterized by single-crystal X-ray diffraction. The crystal structure revealed a nonbonding C-H...O?Fe interaction with a CH3CN molecule. Variable-field Mossbauer spectroscopy of 1-O indicates an intermediate-spin (S = 1) ground state. The Mossbauer parameters for 1-O include an unusually small quadrupole splitting for a triplet FeIV(O) and are reproduced well by density functional theory calculations. With the aim of investigating the initial step for C-F hydroxylation, two new ligands were synthesized, N4Py2Ar2 (L2, Ar2 = -2,6-difluoro-4-methoxyphenyl) and N4Py2Ar3 (L3, Ar3 = -2,6-difluoro-3 methoxyphenyl), with -OMe substituents in the meta or ortho/para positions with respect to the C-F bonds. FeII complexes [Fe(N4Py2Ar2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar3)(CH3CN)](ClO4)2 (3) reacted with isopropyl 2-iodoxybenzoate to give the C-F hydroxylated FeIII-OAr products. The FeIV(O) intermediates 2-O and 3-O were trapped at low temperature and characterized. Complex 2-O displayed a C-F hydroxylation rate similar to that of 1-O. In contrast, the kinetics (via stopped flow UV-vis) for complex 3-O displayed a significant rate enhancement for C-F hydroxylation. Eyring analysis revealed the activation barriers for the C-F hydroxylation reaction for the three complexes, consistent with the observed difference in reactivity. A terminal FeII(OH) complex (4) was prepared independently to investigate the possibility of a nucleophilic aromatic substitution pathway, but the stability of 4 rules out this mechanism. Taken together the data fully support an electrophilic C-F hydroxylation mechanism. PMID- 27656777 TI - Optimization and in Vivo Validation of Peptide Vectors Targeting the LDL Receptor. AB - Active targeting and delivery to pathophysiological organs of interest is of paramount importance to increase specific accumulation of therapeutic drugs or imaging agents while avoiding systemic side effects. We recently developed a family of new peptide ligands of the human and rodent LDL receptor (LDLR), an attractive cell-surface receptor with high uptake activity and local enrichment in several normal or pathological tissues (Malcor et al., J. Med. Chem. 2012, 55 (5), 2227). Initial chemical optimization of the 15-mer, all natural amino acid compound 1/VH411 (DSGL[CMPRLRGC]cDPR) and structure-activity relationship (SAR) investigation led to the cyclic 8 amino acid analogue compound 22/VH445 ([cMPRLRGC]c) which specifically binds hLDLR with a KD of 76 nM and has an in vitro blood half-life of ~3 h. Further introduction of non-natural amino acids led to the identification of compound 60/VH4106 ([(d)-"Pen"M"Thz"RLRGC]c), which showed the highest KD value of 9 nM. However, this latter analogue displayed the lowest in vitro blood half-life (~1.9 h). In the present study, we designed a new set of peptide analogues, namely, VH4127 to VH4131, with further improved biological properties. Detailed analysis of the hLDLR-binding kinetics of previous and new analogues showed that the latter all displayed very high on rates, in the 106 s-1.M-1 range, and off-rates varying from the low 10-2 s-1 to the 10-1 s-1 range. Furthermore, all these new analogues showed increased blood half-lives in vitro, reaching ~7 and 10 h for VH4129 and VH4131, respectively. Interestingly, we demonstrate in cell-based assays using both VH445 and the most balanced optimized analogue VH4127 ([cM"Thz"RLRG"Pen"]c), showing a KD of 18 nM and a blood half-life of ~4.3 h, that its higher on-rate correlated with a significant increase in both the extent of cell-surface binding to hLDLR and the endocytosis potential. Finally, intravenous injection of tritium-radiolabeled 3H VH4127 in wild-type or ldlr -/- mice confirmed their active LDLR targeting in vivo. Overall, this study extends our previous work toward a diversified portfolio of LDLR-targeted peptide vectors with validated LDLR-targeting potential in vivo. PMID- 27656778 TI - Quantitative weight-of-evidence analysis of the persistence, bioaccumulation, toxicity, and potential for long-range transport of the cyclic volatile methyl siloxanes. AB - Cyclic volatile methyl siloxanes (cVMSs) are highly volatile and have an unusual combination of physicochemical properties, which are unlike those of halocarbon based chemicals used to establish criteria for identification of persistent organic pollutants (POPs) that undergo long-range transport (LRT). A transparent quantitative weight of evidence (QWoE) evaluation was conducted to characterize their properties. Measurements of concentrations of cVMSs in the environment are challenging, but currently, concentrations measured in robust studies are all less than thresholds of toxicity. The cVMSs are moderately persistent in air with half-lives <=11 d (greater than the criterion of 2 d) but these compounds partition into the atmosphere, the final sink. The cVMSs are rapidly degraded in dry soils, partition from wet soils into the atmosphere, and are not classifiable as persistent in soils. Persistence in water and sediment is variable, but the greatest concentrations in the environment are observed in sediments. Based upon the measurements that have been made in the environment, cVMSs should not be classified as persistent. Studies in food webs support a conclusion that the cVMSs do not biomagnify, a conclusion that is consistent with results of toxicokinetic studies. Concentrations in air in remote locations are small and deposition has not been detected. Taken together, evidence indicates that traditional measures of persistence and biomagnification used for legacy POP are not suitable for cVMS. Refined approaches used here suggest that cVMSs are not classifiable as persistent, bioaccumulative, or toxic. Further, these chemicals do not undergo LRT in the sense of legacy POPs. PMID- 27656779 TI - Prion diseases: New considerations. AB - The transmissible spongiform encephalopathies, which include Creutzfeldt-Jakob disease, are fatal neurodegenerative disorders caused by the pathological accumulation of abnormal prion protein. The diagnosis of Creutzfeldt-Jakob disease is complex. The electroencephalogram, magnetic resonance imaging, lumbar puncture and genetic testing findings can help in the differential diagnosis of rapidly progressive dementia. There has recently been considerable debate as to whether proteins involved in the development of neurodegenerative diseases should be regarded as prions or only share prion-like mechanisms. Two recent reports described the detection of abnormal prion protein in the nasal mucosa and urine of patients with Creutzfeldt-Jakob disease. These findings raise major health concerns regarding the transmissibility of human prion diseases. We set out to address this neurological hot topic and to draw conclusions on the basis of what is known in the literature thus far. PMID- 27656780 TI - Intervention for A randomized trial of unruptured brain arteriovenous malformations (ARUBA) - Eligible patients: An evidence-based review. AB - While intervention for ruptured arteriovenous malformations (AVMs) of the brain is typically warranted, the management of unruptured AVMs remains controversial. Despite numerous retrospective studies, only one randomized controlled trial has been conducted, comparing the role of medical management alone to medical management plus surgical and/or radiosurgical intervention in patients with unruptured AVMs: A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). To great controversy, ARUBA concluded that medical management alone was superior to intervention for unruptured AVMs, which was subsequently challenged by various single-institution and multi-center studies analyzing outcomes of ARUBA-eligible patients. This review summarizes studies returned from a PubMed database search querying, 'ARUBA,' 'ARUBA-eligible,' 'surgery unruptured AVM,' and "radiosurgery unruptured AVM". The rates of the primary endpoint of symptomatic stroke or death were low among the analyzed studies (0-12.2%, mean 8.0%) and similar to the medically managed arm of ARUBA (10.1%). Likewise, the percentage of patients with impaired functional outcomes (modified Rankin score >=2) in the reviewed studies was low (5.9%-13.1%; mean: 9.9%) and comparable to the 14.0% observed in the medically management arm of ARUBA. The key findings of ARUBA and subsequent work in its aftermath are overviewed and analyzed for the role of surgery and/or radiosurgery in patients with unruptured AVMs. PMID- 27656781 TI - Medicolegal-Malpractice and Ethical Issues in Radiology. PMID- 27656782 TI - Minimally Invasive Posterior Decompression Combined With Percutaneous Pedicle Screw Fixation for the Treatment of Thoracolumbar Fractures With Neurological Deficits: A Prospective Randomized Study Versus Traditional Open Posterior Surgery. AB - STUDY DESIGN: Prospective randomized cohort study. OBJECTIVE: To compare the surgical results of minimally invasive posterior decompression combined with percutaneous pedicle screws fixation (minimally invasive surgery [MIS]) and posterior open surgery (OS) for the treatment of thoracolumbar fracture with neurological deficits. SUMMARY OF BACKGROUND DATA: Thoracolumbar fracture with neurological deficits usually undergoes surgical intervention. OS can achieve satisfied results, but the main disadvantage is approach-related complications. No study, however, focused on the treatment of this disease by MIS through posterior approach. METHODS: Sixty consecutive cases of thoracolumbar fractures with neurological deficits were randomized into MIS group and OS group. Incision length, blood loss, postoperative drainage volume, hospitalization days, blood transfusion rate, analgesic use rate, and x-ray exposure time were used to evaluate the perioperative information and Visual Analog Scale (VAS), Japanese Orthopedics Association (JOA) score, and American Spinal Injury Association grade for patients' symptom. For radiological assessment, sagittal Cobb angle, percentage of vertebral height, and vertebral wedging angle were measured. RESULTS: Fifty-nine of sixty patients were followed-up for at least 12 months. MIS group was superior in perioperative information (P < 0.05), except in the operative time (P = 0.165) and x-ray time (P = 0.000). The operative time seemed longer in MIS group, but no significant difference was found. The x-ray time was significantly higher in MIS group. The mean Visual Analog Scale and Japanese Orthopedics Association scores of the final follow-up in MIS group were better than that in OS group (P < 0.05). Patients in both group achieved a similar neurological recovery according to American Spinal Injury Association grade (P = 0.760). A broken screw was found in one patient in MIS group and a broken rod in one patient in OS group. CONCLUSION: MIS group has achieved the similar effect of OS group and it can minimize the approach-related complication. It also faced with some shortages, such as larger radiation dose and longer learning curve. LEVEL OF EVIDENCE: 2. PMID- 27656783 TI - Cervical Endoscopic Laminoplasty for Cervical Myelopathy. AB - STUDY DESIGN: Prospective clinical series. OBJECTIVE: The aim of this study was to evaluate the safety, feasibility, and efficacy of a new minimally invasive laminoplasty technique for patients with cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Posterior decompression is one of the most common surgical interventions for CSM. Conservative posterior approaches require extensive release and extensive retraction of paraspinal muscles and/or treatment of bone (lamina), which leads to postoperative axial neck pain and a decrease in lordosis and range of motion (ROM). METHODS: A total of 45 patients with CSM received cervical microendoscopic laminoplasty (CMEL). Surgery included endoscopy assisted bilateral laminoplasty with spinous process-ligament complex and deep extensor muscle retroposition. Bilateral titanium mini-screws and plates were used for fixation. Effects and axial symptoms were evaluated according to the Japanese Orthopedic Association (JOA) scores for neurological condition and visual analog scales (VAS) for axial neck pain, respectively. Cervical curvature index (CCI) and ROM were evaluated by X-ray. Computerized tomography and magnetic resonance imaging scans evaluated laminar healing and spinal cord decompression. RESULTS: Follow-up ranged from 18 to 48 months (average 28 months). The duration of surgery averaged 119 minutes (range 62-147 min). Average blood loss was 360 mL (range 250-700 mL). Mean JOA scores improved from 8.0 +/- 1.72 preoperatively to 13.29 +/- 1.85 postoperatively. The effects were excellent in 13 cases, good in 25 cases, and fair in 7 cases. Axial symptoms were excellent in 16 cases, good in 18 cases, and fair in 11 cases. The VAS scores of axial pain significantly improved to 2.3 +/- 2.0 at the final follow-up compared with 4.3 +/- 2.1 preoperatively (P < 0.05). The CMEL procedure provided stable reconstruction of expanded laminar arches with no postoperative collapse or door-close. Sagittal spinal canal diameter increased by 1 to 3 mm. There were no differences in the pre- and postoperative CCI and ROM. CONCLUSION: The new CMEL provides stable reconstruction of an expanded laminar arch and causes less damage to the spinous process-ligament complex and the deep extensor muscles than conventional surgical approaches. The CMEL procedure can be used efficiently and safely to treat CSM. LEVEL OF EVIDENCE: N/A. PMID- 27656784 TI - Review of Percutaneous Kyphoplasty in China. AB - STUDY DESIGN: Review article. OBJECTIVE: The article mainly reviewed the development and current situation of percutaneous kyphoplasty (PKP) in China, aiming to introduce native efforts and progress for PKP procedure on the exploring road. SUMMARY OF BACKGROUND DATA: Since PKP was first reported in China in 2002, Chinese orthopedic researchers have performed lots of clinical applications and studies on the treatment of osteoporotic vertebral compression fracture, spinal metastatic tumor, hemangioma, myeloma, vertebral nonunion, and so on. METHODS: We reviewed the papers on PKP published by native researchers in English and Chinese via Pubmed, EMBASE, the Scopus database, and a series of Chinese databases including Wanfang Data, China National Knowledge Infrastructure (CNKI), and the China Science and Technology Journal Database. The large sample capacity researches, convictive systematic analysis, and overviews were mainly elected as convictive evidence to describe the overall situation of clinical outcomes, complications, and the various technical aspects used to improve conventional surgical management and clinical applications of PKP in China. RESULTS: Until October 2015, 211 articles in English and 2352 studies in Chinese about PKP were reported by 1443 Chinese institutions from 22 provinces around China. More than 50976 patients reported through published articles have received the treatment of PKP. With the technique gradually improved, including puncture, bone cement infusion, vertebral expander instruments, diagnosis, and treatment of special type of vertebral fractures, PKP is performed with the better efficacy and less complication. CONCLUSION: With the progression of minimally invasive spinal surgery around the world, PKP in China has been performed with a trend towards a rapid, safe, and effective treatment. Digital, real-time and artificial intelligence are the directions of future development of PKP. LEVEL OF EVIDENCE: 4. PMID- 27656785 TI - The pupil is faster than the corneal reflection (CR): Are video based pupil-CR eye trackers suitable for studying detailed dynamics of eye movements? AB - Most modern video eye trackers use the p-CR (pupil minus CR) technique to deal with small relative movements between the eye tracker camera and the eye. We question whether the p-CR technique is appropriate to investigate saccade dynamics. In two experiments we investigated the dynamics of pupil, CR and gaze signals obtained from a standard SMI Hi-Speed eye tracker. We found many differences between the pupil and the CR signals. Differences concern timing of the saccade onset, saccade peak velocity and post-saccadic oscillation (PSO). We also obtained that pupil peak velocities were higher than CR peak velocities. Saccades in the eye trackers' gaze signal (that is constructed from p-CR) appear to be excessive versions of saccades in the pupil signal. We conclude that the pupil-CR technique is not suitable for studying detailed dynamics of eye movements. PMID- 27656786 TI - Giving meaning to illness: An investigation of self-defining memories in patients with relapsing-remitting multiple sclerosis patients. AB - Multiple sclerosis (MS) patients are often unable to adequately fulfill their established roles due to physical disabilities and cognitive changes, making this chronic illness particularly threatening to personal identity. Twenty-five MS patients and 25 healthy controls were asked to recall five self-defining memories (SDM). Overall characteristics of SDM did not differ between patients and controls; MS patients displayed preserved capacity to draw meaning upon past events. Moreover, almost two-thirds of MS patients mentioned at least one illness related SDM and about 25% of patients' SDM referred to MS. These memories were experienced as more negative and associated with more tension than other SDM but led toward more positive emotion and less negative emotion over time; they were also more central and more integrated to the personal identity. We concluded that self-challenging events due to MS may trigger both cognitive and emotional processes enabling the integration of illness in patients' self-representations. PMID- 27656787 TI - Artificial consciousness and the consciousness-attention dissociation. AB - Artificial Intelligence is at a turning point, with a substantial increase in projects aiming to implement sophisticated forms of human intelligence in machines. This research attempts to model specific forms of intelligence through brute-force search heuristics and also reproduce features of human perception and cognition, including emotions. Such goals have implications for artificial consciousness, with some arguing that it will be achievable once we overcome short-term engineering challenges. We believe, however, that phenomenal consciousness cannot be implemented in machines. This becomes clear when considering emotions and examining the dissociation between consciousness and attention in humans. While we may be able to program ethical behavior based on rules and machine learning, we will never be able to reproduce emotions or empathy by programming such control systems-these will be merely simulations. Arguments in favor of this claim include considerations about evolution, the neuropsychological aspects of emotions, and the dissociation between attention and consciousness found in humans. Ultimately, we are far from achieving artificial consciousness. PMID- 27656790 TI - ...for whom the poll tolls. AB - Two issues dominated last weekend: I the government's, and in particular John Major's, unpopularity and the threat of cuts to public spending. PMID- 27656791 TI - RCN threatens action over Allitt inquiry. AB - The RCN is threatening to take legal action it Health Secretary Virginia Bottomley fails to allow public access to the forthcoming Beverly Allitt inquiry. PMID- 27656789 TI - Effect of Al content on impact resistance behavior of Al-Ti-B4C composite fabricated under air atmosphere. AB - Reaction behavior, mechanical property and impact resistance of TiC-TiB2/Al composite reacted from Al-Ti-B4C system with various Al content via combination method of combustion synthesis and hot pressed sintering under air was investigated. Al content was the key point to the variation of mechanical property and impact resistance. Increasing Al content could increase the density, strength and toughness of the composite. Due to exorbitant ceramic content, 10wt.% and 20wt.% Al-Ti-B4C composites exhibited poor molding ability and machinability. Flexural strength, fracture toughness, compressive strength and impact toughness of 30-50wt.% Al-Ti-B4C composite were higher than those of Al matrix. The intergranular fracture dispersed and defused impact load and restricted crack extension, enhancing the impact resistance of the composite. The composite with 50wt.% Al content owned highest mechanical properties and impact resistance. The results were useful for the application of TiC-TiB2/Al composite in impact resistance field of ceramic reinforced Al matrix composite. PMID- 27656788 TI - Continuation phase intravenous ketamine in adults with treatment-resistant depression. AB - BACKGROUND: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. METHODS: Twelve subjects with treatment-resistant non psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute phase observation, and during continuation and post-continuation follow-up (acute phase remitters only). RESULTS: Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up. LIMITATIONS: This was an uncontrolled feasibility study with a small sample size. CONCLUSIONS: The continuation-phase administration of ketamine at weekly intervals to patients with treatment resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS. GOV IDENTIFIER: NCT02094898. PMID- 27656793 TI - ? AB - Staff member Hugh Jenkins sizes up one of the hi-tech instruments from the 19th century as the Old Operating Theatre Museum in Southwark, London, prepares to reopen after having some cosmetic surgery of its own. New displays will aLso include pre-anaesthetic and antiseptic surgery. PMID- 27656792 TI - Chance to raise concerns on PREP. AB - Nursing organisations now have a chance to raise their concerns about the UKCC's proposals tor continuing education as the final stage of PREP is out for consultation. PMID- 27656794 TI - More work needed in child analgesia. AB - Children in intensive care endure scores of painful invasive procedures without any extra analgesia, a new study shows. The research, in the British /Medical Journal, found that of 181 invasive procedures carried out in the paediatric ITU at the Royal Brompton Hospital, almost a third were done without additional analgesia. The children cried and grimaced in many of the cases where extra pain control was not given. Hilary Herron. Chair of the Royal College of Nursing Paediatric Nursing Society, described the findings as 'disturbing and warned they show more work needs to be done on paediatric pain control. PMID- 27656796 TI - ? AB - Staff nurse Maria Lacey gets a lesson in self-defence from 73 year old martial arts expert Ron Anderson, a former patient at Killingbeck Hospital, Leeds, who ran the lessons to thank staff. PMID- 27656795 TI - Call for review of UK Central Council. AB - Nursing unions have backed calls for a review of the UKCC's professional conduct machinery. This follows the reinstatement of a nurse struck oil after lying about the circumstances surrounding a patient's death. PMID- 27656797 TI - EC laws could affect moonlighting. AB - Thousands of nurses who moonlight may be affected by new European rules designed to stop workers clocking up more than 48 hours a week. PMID- 27656798 TI - ENB to investigate regional advice to purchasers of nurse education. AB - The English National Board is to investigate how regions are providing nursing advice to purchasers of nurse education and training. PMID- 27656799 TI - Nurses warned against salary 'donations'. AB - Nurses at Ealing Hospital have been warned not to donate' their 1.5 per cent pay increase to help managers claw back a budget blowout of L3.2 million. PMID- 27656800 TI - ? AB - A new play using computer games imagery to help young people understand the impact of asthma Is being launched this week in secondary schools throughout the country. Sonic Roar!, developed by ZIP Theatre, Wolverhampton, in support of the British I.ung foundation, features arch villain Constrictorman (left) and The Pollens, along with Dixie, the central character who has asthma. PMID- 27656802 TI - ? AB - Budding friendship: American nurses Kathy Kaufman (left) and Sandra Prowant enjoy tile garden at the Buckinghamshire College of Higher Education, which they are visiting with colleagues front Kutztown University, Pennsylvania, as part of an exchange programme. PMID- 27656801 TI - Rent increases oust students. AB - Massive rent increases in Bath could force Project 2000 students to give up nursing, the Royal College of Nursing warned last week. PMID- 27656803 TI - Dual role in bid to streamline services? AB - By Simon Canning Senior nursing staff at a Surrey hospital will be forced to take on the dual role of unit manager and site night nurse manager in a bid to streamline services. PMID- 27656804 TI - Bottomley does a good reform job. AB - Health Secretary Virginia Bottomley did 'an extremely good job' in securing transitional funding for the Community Care reforms, the architect of the changes said last week. PMID- 27656805 TI - Elderly and child benefits are safe. AB - Universal benefits for children and the elderly are safe for the remainder of this Parliament. But they are likely to be targeted at the needy in the longer term. PMID- 27656806 TI - Seniority doesn't mean better. AB - Seniority and experience do not necessarily mean a nurse is better at triage, a recent A&E conference heard. PMID- 27656807 TI - Elderly on streets are in desperate need of care. AB - Over half of the elderly people living on the streets of London are suffering from a physical illness and are in desperate need of care, a recent study has revealed. PMID- 27656808 TI - Nominations for RCN Council. AB - The RCN is inviting nominations to its Council from these English divisions: East Anglia, North West Thames, South East Thames, North Western, Wessex, West Midlands and Yorkshire. Members at large for Scotland, Northern Ireland and Wales are also being sought, as well as nominations for chair of the Association of Nursing Students and Student member of Council for 1993-95. PMID- 27656809 TI - ENB opposes Project 2000 proposal. AB - A DoH proposal to drop the learning disabilities branch of Project 2000 has sparked criticism from the English National Board, which warns this may 'hasten the demise of learning disabilities nursing'. PMID- 27656811 TI - ? AB - Parents with one child are more likely to complete immunisation programmes than those with bigger families. PMID- 27656810 TI - Holiday jab training is needed. AB - Few practice nurses have had proper vaccination training, although nearly nine out of ten are responsible for selecting the right vaccines for holidaymakers, a new survey shows. PMID- 27656812 TI - Children from big families miss out on jabs. AB - Health visitors and community nurses have been called upon to play a pivitol role to reverse a trend which shows children from large families are more likely to miss out on immunisation than children from smaller families. PMID- 27656813 TI - Volunteers better than health visitors? AB - Unqualified volunteers may be better than health visitors at delivering child development programmes to disadvantaged first time mothers, a new report says. PMID- 27656814 TI - New hope for psoriasis sufferers. AB - Psoriasis sufferers have been offered new hope following the successful completion of a two year trial at the Westminster Hospital in London. PMID- 27656815 TI - Thrombosis foot pump goes on trial. AB - A new foot pump which can cut the risk of deep vein thrombosis after surgery is now being tried out in Britain. PMID- 27656816 TI - Rediscovering caring and healing arts. AB - Most nurses probably feel they relish a challenge. But how many, I wonder, would rub their hands in glee at the thought of simultaneously trying to redefine nursing and transform the health care care system? Not many, but for Professor Jean Watson, Dean of the University of Colorado Health Sciences Centre, these goals have taken on missionary dimensions. PMID- 27656817 TI - Losing patients with smoking. AB - Barry Clifton's article on the freedom to smoke (Freedom up in smoke, Viewpoint, May 26) reminds me of how in 1982 I owned a nursing home which at first did accept smokers. PMID- 27656819 TI - Rescheduling the special interest group. AB - The committee members of the RCN Social Interest Group for Nurses Working Within Day Hospitals/Day Care for Older People would like to apologise to the large number of people who were interested in attending our conference, which unfortunately had to be postponed. PMID- 27656818 TI - Reconsider plans to scrap P2000 branch. AB - I agreed with Paul Smart when he urged the RCN to reconsider its positive reaction to Department of Health proposals to scrap the Project 2000 learning disabilities branch (Reconsider the response, Letters, May 5). PMID- 27656820 TI - Predictable success of Hib vaccine. AB - It is of course wonderful news that the introduction of the Hib immunisation programme has cut the number of Hib meningitis cases by 70 per cent and that almost three-quarters of parents have responded to the campaign promoting the vaccine (News, 12 May). PMID- 27656821 TI - More plain English females please. AB - I had time to read through your May 26 edition while eating a sandwich at my desk, and discovered that of the six writers on your letters page, four were clearly male, and while the gender of the other two was not discernible, they were replying to letters from other males. PMID- 27656822 TI - No more use for general anaesthesia. AB - It has been years since we have used general anaesthesia to test Brain Stem Auditory Evoked Potential, as described in your article Diagnosing hearing loss in children (Clinical, May 19). PMID- 27656823 TI - Information exchange. AB - * It would be most helpful to me if I were able to hear from any renal units who have produced a patient education video. I am at present undertaking an ENB renal nursing course. PMID- 27656824 TI - Sluice talk. PMID- 27656825 TI - Controversial management figure Roger Dyson shares his thoughts with Trevor Clay in the first of a new series of interviews. AB - 'Roger Dyson offers a tough, hard-hitting analysis of the profession and one that will be painful for a great many nurses. But this Honorary' Professor of Health Care Management at the Centre for Health Planning and Management at Keele University has been around in health care for many years and is well acquainted with nurses and nursing. He argues his case convincingly. PMID- 27656826 TI - Verity Pink argues against the disappearance of hospital chaplains. AB - In my first staff nurse post, I was privileged to participate in a retreat for mental health users. It was organised by the hospital chaplain and funded by the League of Friends. PMID- 27656827 TI - Library and Information Services To Support Project 2000 Library and Information Services To Support Project 2000 British Library R&D Report 6088 Capital Planning 138pp L19.50 (incl postage) 0-906011-85-X. AB - Library and Information Services To Support Project 2000: NURLIS Phase 1 is a research report that looks at the provision made by nursing libraries to support Project 2000. PMID- 27656828 TI - The home surgery: child and baby first aid The home surgery: child and baby first aid H Jones Home Surgery 30mins L10.99+L1.51p&p [Formula: see text]. AB - Dr Hilary Jones introduces the viewer to his family in this first of his 'Home Surgery' series. An excellent idea bringing basic first-aid techniques into the home for a very affordable price. PMID- 27656829 TI - A handbook of drugs in nursing practice, 4th edition A handbook of drugs in nursing practice, 4th edition Henney C Dow R MacConnachie A Churchill livingstone 376pp L10.95 0-443-04378-7. AB - The fourth edition of this established reference work follows the format of previous editions. PMID- 27656830 TI - Listings. PMID- 27656831 TI - Induction of Multidrug Resistance of Acute Myeloid Leukemia Cells by Cocultured Stromal Cells via Upregulation of the PI3K/Akt Signaling Pathway. AB - This study aimed to investigate the role of the PI3K/Akt signaling pathway in multidrug resistance of acute myeloid leukemia (AML) cells induced by cocultured stromal cells. Human AML cell lines HL-60 and U937 were adhesion cocultured with human bone marrow stromal cell line HS-5 cells. Such coculturing induced HL-60 and U937 cells resistant to chemotherapeutic drugs including daunorubicin (DNR), homoharringtonine (HHT), and cytosine arabinoside (Ara-C). The coculturing induced resistance of AML cells to DNR, HHT, and Ara-C can be partially reversed by inhibition of the PI3K/Akt signaling pathway. Clinically, AML patients with a low level of PTEN and a high level of CCND1 had high relapse rates within 1 year, and newly diagnosed AML patients with extramedullary infiltration had a low level of PTEN. This study confirms the involvement of the PI3K/Akt signaling pathway in multidrug resistance in AML cells induced by stroma and suggests that the expression of PTEN and CCND1 may be a prognostic indicator for AML. PMID- 27656832 TI - IGF-I Induces Epithelial-to-Mesenchymal Transition via the IGF-IR-Src-MicroRNA 30a-E-Cadherin Pathway in Nasopharyngeal Carcinoma Cells. AB - Recurrence and distant metastasis are the most common cause of therapeutic failure in nasopharyngeal carcinoma (NPC) patients. Insulin-like growth factor I (IGF-I) can induce epithelial-to-mesenchymal transition (EMT) in many epithelial tumors; however, whether IGF-I can enhance NPC metastasis by EMT and the mechanisms remain unclear. Herein, we have identified that IGF-I could induce EMT and enhance migration ability in NPC cell lines. Furthermore, both Src inhibitor and microRNA-30a (miR-30a) inhibitor reversed IGF-I-induced EMT, suggesting the involvement of an IGF-IR-Src-miR-30a-E-cadherin pathway in IGF-I-induced EMT in NPC cell lines. Overall, the results of the present study may provide more useful information regarding the mechanisms of the IGF-IR signaling pathway in the regulation of NPC metastasis. Both Src kinase and miR-30a can be potential biomarkers for selecting high risk of metastasis in NPC patients. PMID- 27656833 TI - Overexpression of miR-509 Increases Apoptosis and Inhibits Invasion via Suppression of Tumor Necrosis Factor-alpha in Triple-Negative Breast Cancer Hs578T Cells. AB - Triple-negative breast cancer (TNBC) is associated with high recurrence rates of metastasis and death. miR-509 has been reported to be a tumor suppressor in many cancers, but its effect in TNBC has not yet been identified. In this article, we explored the effects of miR-509 on the malignant phenotype of TNBC cells, including proliferation, apoptosis, migration, and invasion. We transiently transfected TNBC cells, Hs578T, with miR-509 mimic. Upon transfection, the expression of miR-509 was upregulated about 50-fold compared with cells transfected with scramble mimic. Overexpression of miR-509 inhibited cell proliferation, induced cell apoptosis, and suppressed cell invasion of Hs578T cells. Moreover, tumor necrosis factor-alpha (TNF-alpha) was involved in miR-509 mediated suppressive effects of TNBC cells, as being treated with TNF-alpha could partially abolish the suppressive effects of miR-509. Collectively, these data suggest that miR-509 could reverse the malignant phenotype of TNBC cells, probably by suppressing TNF-alpha. PMID- 27656834 TI - Knockdown of Histone Methyltransferase hSETD1A Inhibits Progression, Migration, and Invasion in Human Hepatocellular Carcinoma. AB - Our aim was to study the expression of human SET domain containing protein 1A (hSETD1A) in hepatocellular carcinoma patients and its relationship with human hepatocellular carcinoma cell function. A total of 30 patients with hepatocellular carcinoma were enrolled in this study. The expression of hSETD1A was detected by real-time polymerase chain reaction (PCR) and Western blotting. The immortalized normal human liver cell line including SMMC-7721 was subjected to real-time PCR for hSETD1A mRNA. Furthermore, hSETD1A-small hairpin RNA (shRNA) was used to knock down hSETD1A expression in SMMC-7721 cells. Cell proliferation, cell apoptosis, and cell migration were determined by CCK8, flow cytometry, and Transwell assays. The positive expression rate level of hSETD1A mRNA and protein in liver carcinoma tissues was 73.33%. hSETD1A knockdown using a specific hSETD1A shRNA inhibited cell proliferation and promoted cell apoptosis in SMMC-7721 cells. It was also found that downregulation of hSETD1A inhibited cell migration ability but did not affect cell invasion. In conclusion, the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma. PMID- 27656835 TI - Novel BRCA2-Interacting Protein, LIMD1, Is Essential for the Centrosome Localization of BRCA2 in Esophageal Cancer Cell. AB - Mutation of breast cancer 2, early onset (BRCA2) has been identified as a vital risk factor for esophageal cancer (EC). To date, several proteins have been reported as BRCA2-interacting proteins and are associated with multiple biological processes. This study's aim was to identify a novel interactive protein of BRCA2 and to explore its functional roles in EC. A yeast two-hybrid screening was performed to identify a novel BRCA2-interacting protein. Glutathione-S-transferase (GST) pull-down analysis was performed to find out how the binding domain of BRCA2 interacts with LIM domains containing 1 (LIMD1). The interaction between LIMD1 and BRCA2 at the endogenous level was confirmed by using coimmunoprecipitation and immunobloting. Furthermore, two different sequences of short hairpin RNAs (shRNAs) against LIMD1 were transfected into the human EC cell line ECA109. Afterward, the effects of LIMD1 suppression on the centrosome localization of BRCA2 and cell division were analyzed using an immunofluorescence microscope. Results showed that LIMD1 was a novel BRCA2 interacting protein, and LIMD1 interacted with the conserved region of BRCA2 (amino acids 2,750-3,094) in vitro. Importantly, after interfering with the protein expression of LIMD1 in ECA109 cells, the centrosome localization of BRCA2 was significantly abolished and abnormal cell division was significantly increased. These results suggested that LIMD1 is a novel BRCA2-interacting protein and is involved in the centrosome localization of BRCA2 and suppression of LIMD1, causing abnormal cell division in EC cells. PMID- 27656836 TI - TIPE2 Inhibits Hypoxia-Induced Wnt/beta-Catenin Pathway Activation and EMT in Glioma Cells. AB - Hypoxia-induced epithelial-to-mesenchymal transition (EMT) could facilitate tumor progression. TIPE2, the tumor necrosis factor-alpha (TNF-alpha)-induced protein 8 like 2 (also known as TNFAIP8L2), is a member of the TNF-alpha-induced protein 8 (TNFAIP8, TIPE) family and has been involved in the development and progression of several tumors. However, the effects of TIPE2 on the EMT process in glioma cells and the underlying mechanisms of these effects have not been previously reported. In our study, we assessed the roles of TIPE2 in the EMT process in glioma cells in response to hypoxia. Our results indicated that TIPE2 expression was significantly decreased in human glioma cell lines. TIPE2 overexpression significantly inhibited hypoxia-induced migration and invasion, as well as suppressed the EMT process in glioma cells. Furthermore, TIPE2 overexpression prevented hypoxia-induced expression of beta-catenin, cyclin D1, and c-myc in human glioma cells. In summary, these data suggest that TIPE2 overexpression inhibited hypoxia-induced Wnt/beta-catenin pathway activation and EMT in glioma cells. PMID- 27656837 TI - Suppression of Ubiquitin-Specific Peptidase 17 (USP17) Inhibits Tumorigenesis and Invasion in Non-Small Cell Lung Cancer Cells. AB - Recently, deubiquitinating enzymes (DUBs) are emerging as new regulators in cancer progression. However, understanding of the involvement of DUBs in non small cell lung cancer (NSCLC) is just beginning. In this study, we investigated the expression and biological function of ubiquitin-specific peptidase 17 (USP17) in NSCLC progression in vitro and in vivo. We found that the expression of USP17 was higher than in a normal control. We further efficiently depleted USP17 expression in two different NSCLC cells, A549 and H1299. The anchorage independent growth ability of these cells, estimated by soft agar colony formation assay, was significantly reduced after USP17 knockdown. Moreover, Matrigel-Transwell analysis showed that suppression of USP17 decreased cell migration and invasion capacity. Molecular mechanism studies found that USP17 silencing downregulated the expression of matrix metalloproteases (MMP3 and MMP9) in NSCLC cells. Furthermore, animal model results showed that USP17 suppression inhibited NSCLC tumorigenesis and growth. Altogether, this study illustrates the important functions of USP17 in NSCLC and suggests that USP17 might be an attractive target for NSCLC therapy. PMID- 27656838 TI - Knockdown of CUL4B Suppresses the Proliferation and Invasion in Non-Small Cell Lung Cancer Cells. AB - Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, was found to be overexpressed in many types of tumors. However, the expression pattern and role of CUL4B in non-small cell lung cancer (NSCLC) remain largely unknown. Therefore, in the present study, we investigated the role of CUL4B in NSCLC, and the underlying mechanism was also explored. Our results showed that CUL4B was highly expressed in NSCLC cell lines. Silencing CUL4B obviously inhibited proliferation and migration/invasion of NSCLC cells, and it also suppressed the epithelial-mesenchymal transition (EMT) progress in NSCLC cells. Furthermore, knockdown of CUL4B significantly inhibited the expression of beta-catenin, cyclin D1, and c-Myc in NSCLC cells. Taken together, these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/beta-catenin signaling pathway in NSCLC cells. Therefore, CUL4B may represent a novel therapeutic target for the treatment of NSCLC. PMID- 27656839 TI - Knockdown of PARP-1 Inhibits Proliferation and ERK Signals, Increasing Drug Sensitivity in Osteosarcoma U2OS Cells. AB - Poly(ADP-ribose) polymerase 1 (PARP-1) is reported to be involved in DNA repair and is now recognized as a key regulator in carcinogenesis. However, the potential role and the molecular mechanism underlying the effect of PARP-1 on osteosarcoma (OS) cells have not been elucidated. In this study, the results showed that knockdown of PARP-1 resulted in decreased cell proliferation, increased cell apoptosis, and G0/G1 phase arrest in U2OS cells. In addition, increased expression of active caspase 3 and Bax, but reduced Bcl-2, cyclin D1, and phosphorylated extracellular signal regulated kinase 1/2 (pERK1/2) were observed in PARP-1 knockdown in U2OS cells. Moreover, knockdown of PARP-1 correlated with elevated chemosensitivity of U2OS cells to cisplatin through inactivation of the ERK1/2 signaling pathway. In conclusion, our findings demonstrated that PARP-1 plays an important role in regulating OS growth, combining PARP-1 gene therapy with traditional chemotherapy, and may serve as a promising approach to OS therapy. PMID- 27656841 TI - High-resolution, preparative purification of PEGylated protein using a laterally fed membrane chromatography device. AB - We discuss the use of a laterally-fed membrane chromatography (or LFMC) device for single-step purification of mono-PEGylated lysozyme. Recent studies have shown such LFMC devices to be suitable for high-resolution, multi-component separation of proteins in the bind-and-elute mode. The device used in this study contained a stack of rectangular cation-exchange membranes having 9.25mL bed volume. PEGylation of lysozyme was carried out in batch mode using 5kDa methoxy polyethyleneglycol propionaldehyde (or m-PEG propionaldehyde) in the presence of sodium cyanoborohydride as reducing agent. Membrane chromatographic separation was carried out at 1.62 membrane bed volumes per minute flow rate, in the bind and-elute mode. When a salt gradient was applied, the higher PEGylated forms of lysozyme (i.e. the byproducts) eluted earlier than mono-PEGylated lysozyme (the target product), while lysozyme eluted last. Under elution conditions optimized for resolution and speed, the separation could be carried out in less than 15 membrane bed volumes. High purity and recovery of mono-PEGylated lysozyme was obtained. The resolution of separation of mono-PEGylated lysozyme obtained under the above condition was comparable to that reported in the literature for equivalent cation-exchange resin columns while the flow rate expressed in bed volumes/min was 21.7 times higher. Also, the number of theoretical plates per meter was significantly higher with the LFMC device. Therefore the LFMC based purification process discussed in this paper combined high-productivity with high resolution. PMID- 27656842 TI - QuickStats: Percentage* of Adults? Aged >=65 Years Meeting 2008 Federal Guidelines for Leisure-Time AerobicS and Muscle-Strengthening Activities, by Age and Type of Activity - United States, 2000-2002 and 2013-2015. AB - From 2000-2002 to 2013-2015, the percentage of older adults who met the 2008 federal guidelines for aerobic activity increased from 35.7% to 42.5% among persons aged 65-74 years, from 24.5% to 30.9% among persons aged 75-84 years, and from 11.9% to 19.4% among persons aged >=85 years. The percentage who met the guidelines for muscle strengthening activities increased from 11.7% to 19.3% among those aged 65-74 years, from 9.6% to 14.6% among those aged 75-84 years, and from 6.5% to 10.4% among those aged >=85 years. In both periods, within each age group participation declined with age and was lower for muscle strengthening activities compared with aerobic activities. PMID- 27656840 TI - Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial. AB - A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients. PMID- 27656843 TI - Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey. AB - Background Familial Mediterranean fever (FMF) is an inherited inflammatory disorder characterized by attacks of fever with polyserositis. Objective The purpose of this study was to evaluate pediatric patients with FMF who had central nervous system (CNS) findings. Materials and Methods Our medical records database for 2003 to 2014 was screened retrospectively. In total, 104 patients with FMF were identified, 22 of whom had undergone neurological examination for CNS symptoms. Results Neurological findings included headache in 16 patients (72.7%), epilepsy in 6 patients (27.3%), pseudotumor cerebri in 2 patients (9.1%), tremor in 2 patients (9.1%), and multiple sclerosis in 1 patient (4.5%). The most common MEFV gene mutation was homozygous M694V (40.9%). Conclusions Patients with FMF can present with various CNS manifestations. Further studies that include large populations are needed to elucidate the neurological manifestations of FMF. PMID- 27656845 TI - Medicine and humanism. PMID- 27656844 TI - Association of Specific Traumatic Experiences With Alcohol Initiation and Transitions to Problem Use in European American and African American Women. AB - BACKGROUND: The aims of this study were to (i) characterize racial differences in alcohol involvement and (ii) examine the risk conferred by specific trauma exposures and posttraumatic stress disorder (PTSD) for different stages of alcohol involvement in European American (EA) and African American (AA) women. METHODS: Data are from the Missouri Adolescent Female Twins Study (N = 3,787, 14.6% AA; mean age at most recent interview = 24.5 [SD 2.8]). Trauma exposures (e.g., sexual abuse [SA], physical abuse [PA], witnessing another person being killed or injured, experiencing an accident, and experiencing a disaster) were modeled as time-varying predictors of alcohol initiation, transition to first alcohol use disorder (AUD) symptom, and transition to AUD diagnosis using Cox proportional hazards regression while taking into account other substance involvement, parental characteristics, and commonly co-occurring psychiatric disorders. RESULTS: In EA women only, SA was associated with alcohol initiation prior to the age of 14, PA predicted transition from initiation to first AUD symptom, and PA, witnessing injury or death, and SA predicted transition to AUD diagnosis. No association was discovered between trauma exposures or PTSD for any stage of alcohol involvement in AA women. CONCLUSIONS: Results reveal trauma experiences as important contributors to all stages of alcohol involvement in EA women only, with different trauma types conferring risk for each stage of alcohol involvement. PTSD was not revealed as a significant predictor of AUD in EA or AA women, suggesting trauma, independent of PTSD, directly contributes to alcohol involvement. Findings highlight the importance of considering racial differences when developing etiologic models of the association of traumatic experiences with alcohol involvement. PMID- 27656846 TI - Treatment of brain metastases. PMID- 27656847 TI - Pulmonary Kaposi's sarcoma in a female patient: Case report. AB - Kaposi's sarcoma (KS) is a multicentric lymphoproliferative malignancy. Most of the time this tumor is confined to the skin and subcutaneous tissue, but it can present with widespread visceral involvement, such as in the lung. Pulmonary KS is the most frequent form in young adult males, in a ratio of 15:1. The disease usually affects individuals with low CD4 lymphocyte counts (<150-200 cells/mm3). We report a case of a female patient aged 35 years, with the presence of skin lesions, self-limiting episodes of diarrhea and weight loss of 15 kg for nearly 9 months, progressing to persistent fever. AIDS was diagnosed and biopsy of the lesions revealed Kaposi's sarcoma. Computed tomography of the chest showed peribronchovascular thickening, areas of ground glass opacity, condensations with air bronchograms surrounded by ground glass opacity (halo sign) and bilateral pleural effusion. The diagnosis of pulmonary KS is still a challenge, especially due to the occurrence of other opportunistic diseases that may also occur concurrently. Therefore, suspecting this diagnosis based on clinical and laboratory manifestations, and even more with CT findings, is fundamental, especially in patients who already have the cutaneous form of the disease. PMID- 27656848 TI - Histopathological features of post-mortem pituitaries: A retrospective analysis. AB - OBJECTIVE: As a result of the use of neuroimaging techniques, silent pituitary lesions are diagnosed more and more frequently; however, there are few published post-mortem studies about this gland. Incidence data of pituitary lesions are rare and in Portugal they are outdated or even non-existent. The aim of this study is to determine the prevalence of normal patterns and incidental post mortem pituitary pathology at Centro Hospitalar Lisboa Norte, analyzing the associations with clinical data and assessing the clinical relevance of the findings. METHOD: We reviewed retrospectively and histologically 167 pituitaries of a consecutive series of autopsies from the Department of Pathology of this centre. They were done between 2012 and 2014, and in all cases medical records were reviewed. The morphological patterns observed, were classified into three major groups: 1) Normal histological patterns and variants; 2) Infectious inflammatory pathology, metabolic and vascular disorders; 3) Incidental primary proliferation and secondary to systemic diseases. RESULTS: The subjects included in this study were of all age groups (from 1 day to 91 years old), 71 were female and 96 male. Fifty-seven of these glands didn't show any alteration; 51 showed colloid cysts arising from Rathke cleft; 44 presented hyperplasia in adenohypophysis and we identified 20 adenomas in 19 glands (immunohistochemically, eight PRL-producing and five ACTH-producing tumors), ten of which associated with obesity, 11 to hypertension and six to diabetes mellitus. There were two cases with metastasis. CONCLUSION: Subclinical pathology in our country is similar to that seen in other parts of the world, but at older ages. PMID- 27656849 TI - Disease-free survival in patients with non-metastatic breast cancer. AB - INTRODUCTION: Breast cancer is the second most common malignancy in the world and the one with highest incidence in the female population; it is also a major cause of death from cancer among women. OBJECTIVE: To analyze the disease-free survival (DFS) at 5 years and prognostic factors in women with non-metastatic invasive breast cancer treated at a referral center for cancer care located in a medium sized city in the Southeast of Brazil. METHOD: Patients diagnosed with the disease between 2003 and 2005 and identified through the institution's cancer hospital records were analyzed. The follow-up of cases was carried out through hospital records, and complemented by search in the database of the Mortality Information System (SIM) as well as telephone contact. The variables analyzed were distributed in the following blocks: socio-demographic data, tumor-related characteristics, and treatment-related characteristics. Survival functions were calculated using the Kaplan-Meier method and the prognostic factors were analyzed based on Cox proportional hazard model. RESULTS: The study showed a DFS at 5 years of 72% (95CI 67.6-75.9). The main variables independently associated with DFS were lymph node involvement, use of hormone therapy, and education level. CONCLUSION: This study reinforces the importance of early diagnosis for DFS, pointing to the role of social aspects in this regard. The relevance of this research in the country is also highlighted, given the scarcity of studies on DFS in the Brazilian population. PMID- 27656850 TI - Growth curves in Down syndrome with congenital heart disease. AB - INTRODUCTION: To assess dietary habits, nutritional status and food frequency in children and adolescents with Down syndrome (DS) and congenital heart disease (CHD). Additionally, we attempted to compare body mass index (BMI) classifications according to the World Health Organization (WHO) curves and curves developed for individuals with DS. METHOD: Cross-sectional study including individuals with DS and CHD treated at a referral center for cardiology, aged 2 to 18 years. Weight, height, BMI, total energy and food frequency were measured. Nutritional status was assessed using BMI for age and gender, using curves for evaluation of patients with DS and those set by the WHO. RESULTS: 68 subjects with DS and CHD were evaluated. Atrioventricular septal defect (AVSD) was the most common heart disease (52.9%). There were differences in BMI classification between the curves proposed for patients with DS and those proposed by the WHO. There was an association between consumption of vitamin E and polyunsaturated fatty acids. CONCLUSION: Results showed that individuals with DS are mostly considered normal weight for age, when evaluated using specific curves for DS. Reviews on specific curves for DS would be the recommended practice for health professionals so as to avoid precipitated diagnosis of overweight and/or obesity in this population. PMID- 27656852 TI - Epidemiological profile and prognostic factors in patients with lung cancer. AB - OBJECTIVE: To describe the epidemiological profile of patients with lung cancer treated at a public tertiary referral hospital specializing in oncology, and to explore variables that may be related to the overall survival (OS) of these patients. METHOD: Data from the medical records of all patients with invasive lung cancer consecutively seen at the Oncology Department of Hospital Estadual Mario Covas between August 2008 and December 2013 were extracted. The information obtained was submitted to statistical analysis. RESULTS: Of the total 210 patients, 39 were excluded from analysis due to lack of information in the medical record. The most common histological type was adenocarcinoma, representing 39.41% of the sample, followed by squamous cell carcinoma with 25.29% and small-cell carcinoma with 13.53%. Other histological types were responsible for the remaining 21.76%. There was a statistically significant association between Karnofsky performance status (KPS) <= 70%, palliative chemotherapy lines performed and stage at diagnosis, and OS. Additionally, administration of target therapy to patients with EGFR mutation was associated with significantly better overall survival. However, analysis of laboratory variables (hemoglobin, albumin and LDH) as possible prognostic factors for survival showed no statistically significant relationship. Among patients with stage III and IV, the median OS was 10.1 months. CONCLUSION: The risk factors for shorter OS were KPS score <= 70%, less than two lines of palliative chemotherapy, and stage III and IV at diagnosis. The implementation of CT screening for risk patients may allow earlier diagnosis of cases and improve these results. PMID- 27656851 TI - Ductal carcinoma in situ of the breast: Evaluation of main presentations on magnetic resonance imaging compared with findings on mammogram and histology. AB - OBJECTIVE: The purpose of this study was to evaluate the various morphologies and kinetic characteristics of the ductal carcinoma in situ (DCIS) on breast magnetic resonance imaging (MRI) exam, to establish which are the most prevalent and to determine the effectiveness of the method in the detection of DCIS. METHOD: A prospective observational study, starting in May 2014. We evaluated 25 consecutive patients with suspicious or highly suspicious microcalcifications on mammography screening, BI-RADS categories 4 and 5, who underwent breast MRI and then surgery with proven diagnosis of pure DCIS. Surgery was considered the gold standard for correlation between histologic findings and radiological findings obtained on MRI. RESULTS: The most frequent morphological characteristic of DCIS on MRI was non-mass-like enhancement (NMLE), p<0.001, observed in 22/25 (88%) patients (95CI 72.5-100). Of these, segmental distribution was the most prevalent, represented by 9/22 (40.91%) cases (95CI 17.4-64.4), p=0.306, and a clumped internal enhancement pattern was most commonly characterized in DCIS, observed in 13/22 (50.09%) cases. CONCLUSION: DCIS has a wide variety of imaging features on MRI and being able to recognize these lesions is crucial. Its most common morphological presentation is non-mass-like enhancement, while segmental distribution and a clumped internal enhancement pattern are the most common presentations. Faced with the combined analysis of these findings, percutaneous core needle biopsy (core biopsy) or vacuum-assisted biopsy (VAB) should be encouraged. PMID- 27656853 TI - ANCA-positive vasculitis: Clinical implications of ANCA types and titers. AB - INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease that can affect multiple organs, the kidney being one of the most affected. Apart from the diagnostics value of ANCA, they have also been advocated as biomarkers of the disease activity. Recently, the genetic changes found in polyangiitis associated with serine-protease proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA raised the possibility of immune-pathogenic and therapeutic differences. OBJECTIVE: To identify differences in the number of relapses, inflammatory markers, outcomes and renal histology related to the types of ANCA. To analyze the implications of ANCA titers in prognosis. METHOD: A retrospective observational study in a Portuguese tertiary hospital. RESULTS: There were no differences in the progression of renal function, histological pattern and initial treatment with regard to ANCA subtypes. As for the evaluated parameters, there were no significant differences according to the types of ANCA, except for mean CRP values within the normal range, which was 6.3+/-1.3 mg/L for MPO-ANCA and 12.4+/-10.14 mg/L for PR3-ANCA (p=0.04). We found that 66.7% of the MPO-ANCA-positive showed no relapses versus 40% in the case of PR3-ANCA-positive. There was no correlation between the ANCA titers at presentation, during remission, and in the last evaluation, and the number of relapses. CONCLUSION: PR3-ANCA patients have a mean CRP value within the normal range significantly higher than that of MPO-ANCA patients (p=0.04), which seems to reveal greater inflammatory activity in the first. PMID- 27656854 TI - Prevalence and factors associated with urinary incontinence in climacteric. AB - OBJECTIVE: To estimate the prevalence and identify associated factors to urinary incontinence (UI) in climacteric women. METHOD: In a cross-sectional study with a stratified random sample, 1,200 women aged between 35 and 72 years were studied, enrolled in the Family Health Strategy in the city of Pindamonhangaba, Sao Paulo. Urinary incontinence was investigated using the International Consultation of Incontinence Questionnaire - Short Form, while associated factors were assessed based on a self-reported questionnaire with socio-demographic, obstetric and gynecological history, morbidities and drug use. The prevalence of urinary incontinence was estimated with a 95% confidence interval (95CI) and the associated factors were identified through multiple logistic regression model performed using Stata software, version 11.0. RESULTS: Women had a mean age of 51.9 years, most were in menopause (59.4%), married (87.5%), Catholic (48.9%), and declared themselves black or brown (47.2%). The mean age of menopause of women with UI was 47.3 years. The prevalence of UI was 20.4% (95CI: 17.8-23.1%). The factors associated with UI were urinary loss during pregnancy (p=0.000) and after delivery (p=0.000), genital prolapse (p=0.000), stress (p=0.001), depression (p=0.002), and obesity (p=0.006). CONCLUSION: The prevalence of UI was lower but similar to that found in most similar studies. Factors associated with the genesis of UI were urinary loss during pregnancy and after delivery, genital prolapse and obesity. PMID- 27656855 TI - Impact of regulatory assessment on clinical studies in Brazil. AB - INTRODUCTION: Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. OBJECTIVE: This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. METHOD: The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. RESULTS: 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. CONCLUSION: Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country's scientific development. PMID- 27656856 TI - Contraception and family planning at the extreme of reproductive life - climacteric. AB - Menopause is an endocrine phenomenon characterized by gradual estrogen decline. This is a stage in a woman's life in which contraception is extremely important as the risks associated with pregnancy and childbirth increase, both maternal issues associated with higher incidence of comorbidities and issues related to fetal abnormalities, mitochondrial abnormalities, or genetic syndromes. On the other hand, there is a growing number of women who have postponed motherhood and need effective contraception, but without prolonging the return to fertility. Long-acting reversible contraceptives (LARCs), low-dose oral hormonal contraceptives and non-oral contraceptives are preferred. The levonorgestrel releasing intrauterine system is a very good alternative that can maintain endometrial protection after menopause. Definitive methods such as tubal ligation and vasectomy are options for couples that already have their offspring. In this review, we present evidence for contraceptive indication and the effects of hormonal methods on climacteric including options for contraception, control of bleeding during perimenopause and of climacteric symptoms, as well as the transition from such methods to hormone therapy if indicated. PMID- 27656858 TI - Stevens-Johnson syndrome and toxic epidermal necrolysis: a review. AB - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These pathologies are considered a hypersensitivity reaction and can be triggered by drugs, infections and malignancies. The drugs most often involved are allopurinol, some antibiotics, including sulfonamides, anticonvulsants such as carbamazepine, and some non-steroid anti-inflammatory drugs (NSAIDs). Necrosis of keratinocytes is manifested clinically by epidermal detachment, leading to scalded skin appearance. The rash begins on the trunk with subsequent generalization, usually sparing the palmoplantar areas. Macular lesions become purplish, and epidermal detachment occurs, resulting in flaccid blisters that converge and break, resulting in extensive sloughing of necrotic skin. Nikolsky's sign is positive in perilesional skin. SJS and TEN are considered to be two ends of the spectrum of one disease, differing only by their extent of skin detachment. Management of patients with SJS or TEN requires three measures: removal of the offending drug, particularly drugs known to be high-risk; supportive measures and active interventions. Early diagnosis of the disease, recognition of the causal agent and the immediate withdrawal of the drug are the most important actions, as the course of the disease is often rapid and fatal. PMID- 27656857 TI - Ebola virus - from neglected threat to global emergency state. AB - OBJECTIVE: This review aims to update knowledge about Ebola virus disease (EVD) and recent advances in its diagnosis, treatment and prevention. METHOD: A literature review was performed using the following databases: ISI Web of Knowledge, PubMed, IRIS, Scopus and the websites of the CDC and the WHO. Additionally, we have included articles and reports referenced in the basic literature search, and news that were considered relevant. RESULTS: The Ebola virus, endemic in some parts of Africa, is responsible for a severe form of hemorrhagic fever in humans; bats are probably its natural reservoir. It is an extremely virulent virus and easily transmitted by bodily fluids. EVD's complex pathophysiology, characterized by immunosuppression as well as stimulation of an intense inflammatory response, results in a syndrome similar to septic shock. The diagnosis is difficult due to the initial symptoms that mimic other diseases. Despite the high mortality rates that can amount to 90%, a prophylaxis (chemical or vaccine) or effective treatment does not exist. Two vaccines and experimental therapies are being developed for the prevention and treatment of EVD. CONCLUSION: Although the virus is known for about 40 years, the lack of knowledge obtained and the disinterest of government authorities in the countries involved justify the state of emergency currently exists regarding this infectious agent. Only the coordination of multiple entities and the effective commitment of the international community will facilitate the control and effective prevention of EVD. PMID- 27656859 TI - A meta-analysis on uterine transplantation: Redefining the limits of reproductive surgery. AB - In September 2014, the first baby grown in a transplanted uterus was born, which represented an astonishing scientific progress that will mark the history of human reproduction. The recipient was a 32-year-old woman with Rokytanski syndrome who became pregnant after a successful embryo transfer and had an uneventful pregnancy, giving birth to a healthy newborn and marking the beginning of a new era. Patients who do not have a uterus or have a dysfunctional uterus now have the chance of dreaming with pregnancy and motherhood. Combining principles of solid organ transplantation and techniques of human reproduction, uterus transplantation is the first ephemeral transplant performed in order to promote reproductive potential of women and may be removed after successful pregnancy. Worldwide, 11 uterine transplantations were performed in patients. Of these, seven maintained their reproductive potential, with viable transplanted uteri and regular menstrual cycles. PMID- 27656861 TI - Facile electrosynthesis of nano flower like metal-organic framework and its nanocomposite with conjugated polymer as a novel and hybrid electrode material for highly capacitive pseudocapacitors. AB - The [Cu(btec)0.5DMF] (H4btec=1,2,4,5-benzenetetracarboxylate acid) was electrosynthesized on the graphite working electrode by applying catholic potential. The [Cu(btec)0.5DMF] grows on a graphite surface which results from the coordination of 1,2,4,5-benzenetetracarboxylate anions with Cu2+ cations. The electrosynthesized [Cu(btec)0.5DMF] was characterized by X-ray diffraction, scanning electron microscopy. Furthermore, POAP/Cu(btec)0.5DMF nanocomposite film electrosynthesized on the surface of the carbon paste electrode by cyclic voltammetry. Different electrochemical methods including galvanostatic charge discharge experiments, cyclic voltammetry and electrochemical impedance spectroscopy are carried out in order to investigate the performance of the system. This work introduces new nanocomposite materials for electrochemical redox capacitors with advantages including ease synthesis, high active surface area and stability in an aqueous electrolyte. PMID- 27656860 TI - To ~P or Not to ~P? Non-canonical activation by two-component response regulators. AB - Bacteria sense and respond to their environment through the use of two-component regulatory systems. The ability to adapt to a wide range of environmental stresses is directly related to the number of two-component systems an organism possesses. Recent advances in this area have identified numerous variations on the archetype systems that employ a sensor kinase and a response regulator. It is now evident that many orphan regulators that lack cognate kinases do not rely on phosphorylation for activation and new roles for unphosphorylated response regulators have been identified. The significance of recent findings and suggestions for further research are discussed. PMID- 27656862 TI - Prostate cancer screening: Do guidelines matter? PMID- 27656863 TI - Error in Financial Disclosure. PMID- 27656865 TI - Induced systemic resistance: a delicate balance. PMID- 27656866 TI - Surveillance of Hepatocellular Carcinoma by Magnetic Resonance Imaging With Liver Specific Contrast. PMID- 27656867 TI - Black Gains in Life Expectancy. PMID- 27656864 TI - Budd-chiari syndrome causing acute liver failure: A multicenter case series. AB - Budd-Chiari syndrome (BCS) is a rare disease resulting from obstruction of the hepatic venous outflow tract that typically presents with abdominal pain, jaundice, and ascites without frank liver failure. However, BCS may also evolve more rapidly to acute liver failure (ALF). In this study, we describe the clinical features, treatment, and outcomes of ALF due to BCS and compare our results with those in the published literature. Twenty of the 2344 patients enrolled in the Acute Liver Failure Study Group (ALFSG) registry since 1998 presented with a clinical diagnosis of BCS. An additional 19 patients of ALF-BCS in the English language literature were reviewed and compared with the ALFSG cases. Most ALF-BCS patients were white (84%) and female (84%) in their fourth decade. A hypercoagulable state was noted in 63% of patients. BCS was diagnosed by Doppler ultrasonography or abdominal computed tomography in all patients. Liver biopsies (n = 6) all had evidence of severe pericentral necrosis. Treatments used included most commonly anticoagulation (71%), but also transjugular intrahepatic portosystemic shunt (TIPS; 37%) and orthotopic liver transplantation (37%). In-hospital mortality was approximately 60%. In conclusion, BCS is a rare cause of ALF and mandates prompt diagnosis and management for successful outcomes. Once the diagnosis is confirmed, prompt anticoagulation is recommended in conjunction with evaluation for malignancy or thrombophilic disorder. Mortality may have improved in recent years with use of TIPS and/or orthotopic liver transplantation compared with prior published reports. Liver Transplantation 23 135-142 2017 AASLD. PMID- 27656868 TI - Loss of expression of SMARCA4 (BRG1), SMARCA2 (BRM) and SMARCB1 (INI1) in undifferentiated carcinoma of the endometrium is not uncommon and is not always associated with rhabdoid morphology. AB - AIM: Abnormalities of SMARCB1 (INI1), which encodes a member of the SWI/SNF pathway, are found in neoplasms with rhabdoid morphology, such as malignant rhabdoid tumour of the kidney and atypical teratoid/rhabdoid tumour of the central nervous system. SMARCA4 (BRG1), which encodes another member of the SWI/SNF pathway, and which is mutated in almost all small-cell carcinomas of the ovary, hypercalcaemic type, has been investigated in endometrial carcinomas, and mutations with resultant loss of immunohistochemical staining have been demonstrated in some endometrial undifferentiated carcinomas/dedifferentiated carcinomas. The aim of this study was to evaluate immunohistochemical expression of SMARCA4, SMARCB1 and SMARCA2 in a cohort of undifferentiated endometrial carcinomas, and to correlate expression of these markers with rhabdoid morphology and clinical outcome. METHODS AND RESULTS: Forty undifferentiated endometrial carcinomas (18 pure and 22 dedifferentiated carcinomas) were stained with SMARCA4 (n = 40), SMARCB1 (n = 27), and SMARCA2 (n = 37). SMARCA4 expression was intact in 26 of 40 (65%) cases, lost in 13 of 40 (32.5%) cases, and unassessable in one case (2.5%). SMARCB1 expression was intact in 26 of 27 (96%) cases and lost in one of 27 (4%) cases. SMARCA2 expression was intact in 23 of 37 (62%) cases, lost in 10 of 37 (27%) cases, and unassessable in four cases. SMARCA2 expression showed corresponding loss in nine of the 13 (69%) SMARCA4-deficient cases. Rhabdoid morphology was present in three of 13 (23%) SMARCA4-deficient cases, in two of 10 (20%) SMARCA2-deficient cases, in four of 26 (15%) SMARCA4-intact cases, and in four of 23 (17%) SMARCA2-intact cases. There was no correlation between SMARCA4 or SMARCA2 expression and clinical outcome. CONCLUSIONS: Our study demonstrated that almost one-third of endometrial undifferentiated carcinomas show loss of SMARCA4 and SMARCA2 expression, and that a subset show rhabdoid morphology. The majority of the SMARCA4-deficient cases show concomitant loss of SMARCA2 expression. There is no correlation between SMARCA4 or SMARCA2 expression and outcome. Our results confirm that the SWI/SNF chromatin remodelling complex is involved in the pathogenesis of endometrial undifferentiated carcinomas. PMID- 27656870 TI - Attentional capture by deviant sounds: A noncontingent form of auditory distraction? AB - The occurrence of an unexpected, infrequent sound in an otherwise homogeneous auditory background tends to disrupt the ongoing cognitive task. This "deviation effect" is typically explained in terms of attentional capture whereby the deviant sound draws attention away from the focal activity, regardless of the nature of this activity. Yet, there is theoretical and empirical evidence suggesting that the attention-capture mechanism underlying this form of distraction could rather be triggered in a task-contingent fashion. The present study aimed at determining whether the auditory deviation effect reflects the action of either a stimulus-driven or a task-contingent orienting mechanism. To do so, we conducted a systematic investigation whereby the impact of verbal deviants-a letter embedded in the repetition of another letter-and spatial deviants-a sound presented contralaterally to the other sounds-on verbal and spatial short-term memory (STM) was assessed. This study established that both verbal and spatial deviants can hinder both verbal and spatial order reconstruction (Experiment 1) and missing-item tasks (Experiment 2). Such results demonstrate that the deviation effect reflects a general form of auditory distraction as interference took place both within and across domains and regardless of the processes engaged in the focal task. (PsycINFO Database Record PMID- 27656869 TI - Is conflict adaptation due to active regulation or passive carry-over? Evidence from eye movements. AB - Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system's ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across 2 experiments in which participants had to identify a target stimulus based on an endogenous cue while-on conflict trials having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial-that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. (PsycINFO Database Record PMID- 27656871 TI - Not all order memory is equal: Test demands reveal dissociations in memory for sequence information. AB - Remembering the order of a sequence of events is a fundamental feature of episodic memory. Indeed, a number of formal models represent temporal context as part of the memory system, and memory for order has been researched extensively. Yet, the nature of the code(s) underlying sequence memory is still relatively unknown. Across 4 experiments that manipulated encoding task, we found evidence for 3 dissociable facets of order memory. Experiment 1 introduced a test requiring a judgment of which of 2 alternatives had immediately followed a word during encoding. This measure revealed better retention of interitem associations following relational encoding (silent reading) than relatively item-specific encoding (judging referent size), a pattern consistent with that observed in previous research using order reconstruction tests. In sharp contrast, Experiment 2 demonstrated the reverse pattern: Memory for the studied order of 2 sequentially presented items was actually better following item-specific encoding than following relational encoding. Experiment 3 reproduced this dissociation in a single experiment using both tests. Experiment 4 extended these findings by further dissociating the roles of relational encoding and item strength in the 2 tests. Taken together, these results indicate that memory for event sequence is influenced by (a) interitem associations, (b) the emphasized directionality of an association, and (c) an item's strength independent of other items. Memory for order is more complicated than has been portrayed in theories of memory and its nuances should be carefully considered when designing tests and models of temporal and relational memory. (PsycINFO Database Record PMID- 27656873 TI - The magic of words reconsidered: Investigating the automaticity of reading color neutral words in the Stroop task. AB - In 2 variants of the color-word Stroop task, we compared 5 types of color-neutral distractors-real words (e.g., HAT), pseudowords (e.g., HIX), consonant strings (e.g., HDK), symbol strings (e.g., #$%), and a row of Xs (e.g., XXX)-as well as incongruent color words (e.g., GREEN displayed in red). When participants named the color, relative to a row of Xs, words and pseudowords interfered equally and more than the consonant strings, which in turn interfered more than the symbols. In contrast, when participants identified the color by manual key-press responses, all 5 types of neutral strings produced equal color response latencies. In both tasks, the incongruent color words produced robust interference relative to the color-neutral words. Reaction time (RT) distribution analyses showed that all interference effects (relative to the row of Xs) increased across the quantiles. We interpret these results in terms of an evidence accumulation process in which the interfering distractor reduces the effective rate of evidence accumulation for the color target. We take the results to argue that the task of reading, even when triggered unintentionally, is not an invariant process driven solely by the stimulus properties, and is instead guided by the task goal. (PsycINFO Database Record PMID- 27656872 TI - More is generally better: Higher working memory capacity does not impair perceptual category learning. AB - It is sometimes supposed that category learning involves competing explicit and procedural systems, with only the former reliant on working memory capacity (WMC). In 2 experiments participants were trained for 3 blocks on both filtering (often said to be learned explicitly) and condensation (often said to be learned procedurally) category structures. Both experiments (total N = 160) demonstrated that participants with higher WMC tended to be more accurate in condensation tasks, but not less accurate in filtering tasks. Furthermore, state-trace analysis did not find a differential influence of WMC on performance in these tasks. Finally, inspection of the mixture of response strategies at play across the 2 conditions and 3 blocks showed only a minor influence of WMC, and then only on later training blocks. The results provide no support for the existence of a "system" of category learning that is independent of working memory and are instead consistent with most single-system interpretations of category learning. (PsycINFO Database Record PMID- 27656874 TI - Activation cascading in sign production. AB - In this study, we investigated how activation unfolds in sign production by examining whether signs that are not produced have their representations activated by semantics (cascading of activation). Deaf signers were tested with a picture-picture interference task. Participants were presented with pairs of overlapping pictures and named the green picture (target) while ignoring the red picture (distractor). In Experiment 1 we varied whether target and distractor pictures had similar signs. Signs were produced faster with sign-related picture pairs compared to unrelated picture pairs. The facilitation observed with sign related pairs replicates the 1 obtained in speaking with sound-related pairs (e.g., bed-bell), a finding cited in support of cascading of activation. In Experiments 2A and 2B we focused on sign iconicity, anticipating that cascading of activation would lead to a facilitatory effect of iconicity. Consistent with this prediction, picture distractors with iconic signs induced faster responses. Furthermore, in Experiment 3, facilitation was found for iconic signs in picture naming. Altogether, our results reveal that cascading of activation is a fundamental aspect of language processing that is at play not only in speaking, but also in signing. Our results also help to define which signs are activated in sign production. (PsycINFO Database Record PMID- 27656875 TI - Dasatinib-Induced T-Cell-Mediated Colitis: A Case Report and Review of the Literature. AB - Dasatinib is a potent inhibitor of the altered tyrosine kinase activity in disease states associated with BCR/ABL1. This agent has been shown to exhibit broad off-target kinase inhibition and immunomodulating properties. These effects may be responsible for dasatinib's unique side effects including a distinctive form of hemorrhagic colitis. We report a case of hemorrhagic colitis associated with dasatinib use in a patient with chronic myelogenous leukemia. Colon biopsies at the time of symptomatic colitis confirmed CD3+CD8+ T cell infiltration. The process rapidly resolved following drug discontinuation, but relapsed when rechallenged with a reduced dose of dasatinib. Colitis did not recur when the patient was treated with an alternative agent. A literature review of prior cases involving dasatinib-induced T-cell mediated colitis provides insight into commonalities that may facilitate the recognition and management of this entity. Most incidences occurred after a 3-month drug exposure and may be accompanied by large granular lymphocytes. The process uniformly resolves within a few days following drug discontinuation and will generally recur in a shorter period of time if the drug is reintroduced. Most patients will require an alternative agent, although select patients could be continued on dasatinib if other options are limited. PMID- 27656876 TI - Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia. AB - The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD +/- 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine. PMID- 27656877 TI - The Cerebral Surfactant System and Its Alteration in Hydrocephalic Conditions. AB - INTRODUCTION: Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host's innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. PATIENTS AND METHODS: CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0-84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. RESULTS: SP A-D are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. CONCLUSION: The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP's requires further thorough investigations. PMID- 27656879 TI - The German Version of the Dutch Eating Behavior Questionnaire: Psychometric Properties, Measurement Invariance, and Population-Based Norms. AB - The Dutch Eating Behavior Questionnaire is an internationally widely used instrument assessing different eating styles that may contribute to weight gain and overweight: emotional eating, external eating, and restraint. This study aimed to evaluate the psychometric properties of the 30-item German version of the DEBQ including its measurement invariance across gender, age, and BMI-status in a representative German population sample. Furthermore, we examined the distribution of eating styles in the general population and provide population based norms for DEBQ scales. A representative sample of the German general population (N = 2513, age >= 14 years) was assessed with the German version of the DEBQ along with information on sociodemographic characteristics and body weight and height. The German version of the DEQB demonstrates good item characteristics and reliability (restraint: alpha = .92, emotional eating: alpha = .94, external eating: alpha = .89). The 3-factor structure of the DEBQ could be replicated in exploratory and confirmatory factor analyses and results of multi group confirmatory factor analyses supported its metric and scalar measurement invariance across gender, age, and BMI-status. External eating was the most prevalent eating style in the German general population. Women scored higher on emotional and restrained eating scales than men, and overweight individuals scored higher in all three eating styles compared to normal weight individuals. Small differences across age were found for external eating. Norms were provided according to gender, age, and BMI-status. Our findings suggest that the German version of the DEBQ has good reliability and construct validity, and is suitable to reliably measure eating styles across age, gender, and BMI-status. Furthermore, the results demonstrate a considerable variation of eating styles across gender and BMI-status. PMID- 27656878 TI - Genome Analysis and Characterisation of the Exopolysaccharide Produced by Bifidobacterium longum subsp. longum 35624TM. AB - The Bifibobacterium longum subsp. longum 35624TM strain (formerly named Bifidobacterium longum subsp. infantis) is a well described probiotic with clinical efficacy in Irritable Bowel Syndrome clinical trials and induces immunoregulatory effects in mice and in humans. This paper presents (a) the genome sequence of the organism allowing the assignment to its correct subspeciation longum; (b) a comparative genome assessment with other B. longum strains and (c) the molecular structure of the 35624 exopolysaccharide (EPS624). Comparative genome analysis of the 35624 strain with other B. longum strains determined that the sub-speciation of the strain is longum and revealed the presence of a 35624-specific gene cluster, predicted to encode the biosynthetic machinery for EPS624. Following isolation and acid treatment of the EPS, its chemical structure was determined using gas and liquid chromatography for sugar constituent and linkage analysis, electrospray and matrix assisted laser desorption ionization mass spectrometry for sequencing and NMR. The EPS consists of a branched hexasaccharide repeating unit containing two galactose and two glucose moieties, galacturonic acid and the unusual sugar 6-deoxy-L-talose. These data demonstrate that the B. longum 35624 strain has specific genetic features, one of which leads to the generation of a characteristic exopolysaccharide. PMID- 27656881 TI - Correction: Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma. AB - [This corrects the article DOI: 10.1371/journal.pone.0161103.]. PMID- 27656880 TI - Selenotranscriptomic Analyses Identify Signature Selenoproteins in Brain Regions in a Mouse Model of Parkinson's Disease. AB - Genes of selenoproteome have been increasingly implicated in various aspects of neurobiology and neurological disorders, but remain largely elusive in Parkinson's disease (PD). In this study, we investigated the selenotranscriptome (24 selenoproteins in total) in five brain regions (cerebellum, substantia nigra, cortex, pons and hippocampus) by real time qPCR in a two-phase manner using a mouse model of chronic PD. A wide range of changes in selenotranscriptome was observed in a manner depending on selenoproteins and brain regions. While Selv mRNA was not detectable and Dio1& 3 mRNA levels were not affected, 1, 11 and 9 selenoproteins displayed patterns of increase only, decrease only, and mixed response, respectively, in these brain regions of PD mice. In particular, the mRNA expression of Gpx1-4 showed only a decreased trend in the PD mouse brains. In substantia nigra, levels of 17 selenoprotein mRNAs were significantly decreased whereas no selenoprotein was up-regulated in the PD mice. In contrast, the majority of selenotranscriptome did not change and a few selenoprotein mRNAs that respond displayed a mixed pattern of up- and down-regulation in cerebellum, cortex, hippocampus, and/or pons of the PD mice. Gpx4, Sep15, Selm, Sepw1, and Sepp1 mRNAs were most abundant across all these five brain regions. Our results showed differential responses of selenoproteins in various brain regions of the PD mouse model, providing critical selenotranscriptomic profiling for future functional investigation of individual selenoprotein in PD etiology. PMID- 27656883 TI - HIV-Infected or -Exposed Children Exhibit Lower Immunogenicity to Hepatitis B Vaccine in Yaounde, Cameroon: An Appeal for Revised Policies in Tropical Settings? AB - BACKGROUND: Since 2005, anti-hepatitis B virus (anti-HBV) vaccine is part of the Expanded Program on Immunization (EPI) for infants born in Cameroon, with 99% anti-HBV coverage. In a context of generalized HIV epidemiology, we assessed paediatric anti-HBV vaccine response according to HIV status, feeding option and age in a tropical context. METHODOLOGY: Prospective, observational and cross sectional study conducted among 82 children (27 [IQR: 9-47] months, min-max: 6 59), after complete anti-HBV vaccination (Zilbrix Hepta: 10MUg AgHBs) at the Essos Health Centre in Yaounde, Cameroon, classified as group-A: HIV unexposed (28), group-B: HIV-exposed/uninfected (29), group-C: HIV-infected (25). Quantitative anti-HBs ELISA was interpreted as "no", "low-" or "protective response" with <1, 1-10, or >=10 IU/L respectively; with p-value<0.05 considered significant. RESULTS: Children were all HBV-unexposed (AcHBc-negative) and uninfected (HBsAg-negative). Response to anti-HBV vaccine was 80.49% (66/82), with only 45.12% (37/82) developed a protective-response (>=10IU/L). According to HIV status, 60.71% (17/28) developed a protective-response in group-A, vs. 51.72% (15/29) and 20% (5/25) in group-B and group-C respectively, Odds Ratio (OR): 2.627 [CI95% 0.933-7.500], p = 0.041. According to feeding option during first six months of life, 47.67% (21/45) developed a protective-response on exclusive breastfeeding vs. 43.24% (16/37) on mixed or formula feeding, OR: 1.148 [CI95% 0.437-3.026], p = 0.757. According to age, protective-response decreased significantly as children grow older: 58.33% (28/48) <24 months vs. 26.47% (9/34) >=24 months, OR: 3.889 [CI95% 1.362-11.356], p = 0.004; and specifically 67.65% (23/34) <=6 months vs. 0%, (0/5) 33-41 months, p = 0.008. CONCLUSIONS: Anti-HBV vaccine provides low rate of protection (<50%) among children in general, and particularly if HIV-exposed, infected and/or older children. Implementing policies for early vaccination, specific immunization algorithm for HIV exposed/infected children, and monitoring vaccine response would ensure effective protection in tropical settings, pending extensive/confirmatory investigations. PMID- 27656882 TI - Electron Transport in a Dioxygenase-Ferredoxin Complex: Long Range Charge Coupling between the Rieske and Non-Heme Iron Center. AB - Dioxygenase (dOx) utilizes stereospecific oxidation on aromatic molecules; consequently, dOx has potential applications in bioremediation and stereospecific oxidation synthesis. The reactive components of dOx comprise a Rieske structure Cys2[2Fe-2S]His2 and a non-heme reactive oxygen center (ROC). Between the Rieske structure and the ROC, a universally conserved Asp residue appears to bridge the two structures forming a Rieske-Asp-ROC triad, where the Asp is known to be essential for electron transfer processes. The Rieske and ROC share hydrogen bonds with Asp through their His ligands; suggesting an ideal network for electron transfer via the carboxyl side chain of Asp. Associated with the dOx is an itinerant charge carrying protein Ferredoxin (Fdx). Depending on the specific cognate, Fdx may also possess either the Rieske structure or a related structure known as 4-Cys-[2Fe-2S] (4-Cys). In this study, we extensively explore, at different levels of theory, the behavior of the individual components (Rieske and ROC) and their interaction together via the Asp using a variety of density function methods, basis sets, and a method known as Generalized Ionic Fragment Approach (GIFA) that permits setting up spin configurations manually. We also report results on the 4-Cys structure for comparison. The individual optimized structures are compared with observed spectroscopic data from the Rieske, 4-Cys and ROC structures (where information is available). The separate pieces are then combined together into a large Rieske-Asp-ROC (donor/bridge/acceptor) complex to estimate the overall coupling between individual components, based on changes to the partial charges. The results suggest that the partial charges are significantly altered when Asp bridges the Rieske and the ROC; hence, long range coupling through hydrogen bonding effects via the intercalated Asp bridge can drastically affect the partial charge distributions compared to the individual isolated structures. The results are consistent with a proton coupled electron transfer mechanism. PMID- 27656884 TI - Toward an Objective Diagnostic Test for Bacterial Cellulitis. AB - BACKGROUND: Prior studies repeatedly showed that cultures of skin lesions diagnosed as "cellulitis" are usually negative. However, lack of a gold standard for diagnosis (against which culture might be judged) and failure to assess the human immune response are important limitations of prior work. In this pilot study, we aimed to develop a criterion standard for research on bacterial cellulitis, to evaluate the sensitivity of procalcitonin for bacterial cellulitis, and to use gene expression analysis to find other candidate diagnostic markers. METHODS: We classified lesions via biopsies, 16s rRNA gene detection, culture, and histopathology. We quantified procalcitonin expression in blood. We also used Nanostring technology to quantify transcription of immunomodulators that may distinguish cases from inflamed controls. RESULTS: Of 28 participants, 15 had a clinical diagnosis of cellulitis, six had a diagnosis of non-infectious dermatitis, and seven were normal volunteers. Of the "cellulitis" patients, three (20%) had pathogens isolated, and were designated confirmed cases. Procalcitonin was undetectable in all three. HLA-DQA1 was expressed 34-fold more in confirmed cases vs. controls (fold change of geometric mean). Heat maps depicting multiplex gene expression analysis revealed a distinct profile of gene expression in confirmed cases relative to comparators. CONCLUSIONS: Most "cellulitis" patients had microbiologically-negative biopsies. Procalcitonin was undetectable, and HLA-DQA1 elevated, in confirmed bacterial cases. Multivariable transcriptomic profiling results supported our algorithm's ability to identify patients with true bacterial cellulitis. A larger sample may allow discovery of an immunological signature capable of distinguishing bacterial cellulitis from its mimics in clinical practice. PMID- 27656885 TI - Phylogeographic History of Atraphaxis Plants in Arid Northern China and the Origin of A. bracteata in the Loess Plateau. AB - In China, species of Atraphaxis (Polygonaceae) primarily inhabit arid zones across temperate steppe and desert regions. The complex geologic history (e.g., expansion of deserts) and extreme climate shifts of the region appear to have played an important role in shaping the phylogeography of Atraphaxis. The present study focuses on species-level phylogeographic patterns of Atraphaxis in China, with the goal of determining the impact of past environmental changes, in northern China, on the evolutionary history of the genus. Five hundred and sixty four individuals distributed among 71 populations of 11 species of Atraphaxis from across the geographic range of the genus were studied using sequence data from two plastid spacers, psbK-psbI and psbB-psbH. The results demonstrate that most chloroplast haplotypes are species-specific, except for some present among widespread species. The phylogeny of Atraphaxis was well structured, and molecular dating analyses suggest that the main divergence events occurred during the late Pliocene and Pleistocene (5.73-0.03 million years ago). The statistical dispersal-vicariance analysis (S-DIVA) results provide evidence that phylogeographic patterns for the genus were characterized by both vicariance events and regional dispersal. The presented data suggest that the rapid expansion of deserts and climatic changes in northern China during the late Pliocene and Pleistocene have driven the diversification and spread of Atraphaxis in the region. The expansion of the Tengger Desert provided appropriate conditions for the origin of A. bracteata. Additionally, a contact zone in the north of the Hexi Corridor was identified as having played a significant role as a migratory route for species in adjacent areas. PMID- 27656886 TI - Fungal Endophytes as a Metabolic Fine-Tuning Regulator for Wine Grape. AB - Endophytes proved to exert multiple effects on host plants, including growth promotion, stress resistance. However, whether endophytes have a role in metabolites shaping of grape has not been fully understood. Eight endophytic fungal strains which originally isolated from grapevines were re-inoculated to field-grown grapevines in this study, and their effects on both leaves and berries of grapevines at maturity stage were assessed, with special focused on secondary metabolites and antioxidant activities. High-density inoculation of all these endophytic fungal strains modified the physio-chemical status of grapevine to different degrees. Fungal inoculations promoted the content of reducing sugar (RS), total flavonoids (TF), total phenols (TPh), trans-resveratrol (Res) and activities of phenylalanine ammonia-lyase (PAL), in both leaves and berries of grapevine. Inoculation of endophytic fungal strains, CXB-11 (Nigrospora sp.) and CXC-13 (Fusarium sp.) conferred greater promotion effects in grape metabolic re shaping, compared to other used fungal strains. Additionally, inoculation of different strains of fungal endophytes led to establish different metabolites patterns of wine grape. The work implies the possibility of using endophytic fungi as fine-tuning regulator to shape the quality and character of wine grape. PMID- 27656887 TI - The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer. AB - Breast cancer mortality is primarily due to metastasis rather than primary tumors, yet relatively little is understood regarding the etiology of metastatic breast cancer. Previously, using a mouse genetics approach, we demonstrated that inherited germline polymorphisms contribute to metastatic disease, and that these single nucleotide polymorphisms (SNPs) could be used to predict outcome in breast cancer patients. In this study, a backcross between a highly metastatic (FVB/NJ) and low metastatic (MOLF/EiJ) mouse strain identified Arntl2, a gene encoding a circadian rhythm transcription factor, as a metastasis susceptibility gene associated with progression, specifically in estrogen receptor-negative breast cancer patients. Integrated whole genome sequence analysis with DNase hypersensitivity sites reveals SNPs in the predicted promoter of Arntl2. Using CRISPR/Cas9-mediated substitution of the MOLF promoter, we demonstrate that the SNPs regulate Arntl2 transcription and affect metastatic burden. Finally, analysis of SNPs associated with ARNTL2 expression in human breast cancer patients revealed reproducible associations of ARNTL2 expression quantitative trait loci (eQTL) SNPs with disease-free survival, consistent with the mouse studies. PMID- 27656888 TI - Fetal Myelomeningocele Repair through a Mini-Hysterotomy. AB - OBJECTIVE: To present the feasibility of fetal myelomeningocele (MMC) repair through a mini-hysterotomy and to describe the perinatal results from our initial experience. METHODS: A descriptive study of cases of fetal MMC correction via mini-hysterotomy performed between 2014 and 2016. RESULTS: Forty-five women underwent fetal surgery and 87% (39/45) delivered. A complete multilayer correction of the MMC was possible in all cases. There were no maternal, fetal or neonatal deaths. No maternal or fetal complications occurred from fetal MMC correction until maternal hospital discharge. The average gestational age (GA) at surgery was 24.5 weeks (standard deviation, SD: 1.7; range: 20.7-26.9). The median hysterotomy length was 3.05 cm (SD: 0.39; range: 2.50-3.50). One patient (1/39; 2.6%) experienced chorioamniotic separation. Nine patients (9/39; 23.1%) had premature preterm rupture of membranes at a median GA of 34.1 weeks (range: 31.1-36.0). The average GA at delivery was 35.3 weeks (SD: 2.2; range: 27.9 39.1). Ninety-five percent (37/39) of our patients had an intact hysterotomy site at delivery. Ventriculoperitoneal shunt placement was necessary for 7.7% (3/39) of the neonates. CONCLUSION: Fetal MMC repair is feasible through a mini hysterotomy. This approach appears to be associated with reduced risks of very preterm delivery and maternal, fetal and neonatal complications. PMID- 27656890 TI - The Lipopolysaccharide-Induced Metabolome Signature in Arabidopsis thaliana Reveals Dynamic Reprogramming of Phytoalexin and Phytoanticipin Pathways. AB - Lipopolysaccharides (LPSs), as MAMP molecules, trigger the activation of signal transduction pathways involved in defence. Currently, plant metabolomics is providing new dimensions into understanding the intracellular adaptive responses to external stimuli. The effect of LPS on the metabolomes of Arabidopsis thaliana cells and leaf tissue was investigated over a 24 h period. Cellular metabolites and those secreted into the medium were extracted with methanol and liquid chromatography coupled to mass spectrometry was used for quantitative and qualitative analyses. Multivariate statistical data analyses were used to extract interpretable information from the generated multidimensional LC-MS data. The results show that LPS perception triggered differential changes in the metabolomes of cells and leaves, leading to variation in the biosynthesis of specialised secondary metabolites. Time-dependent changes in metabolite profiles were observed and biomarkers associated with the LPS-induced response were tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indole-and other glucosinolates, indole derivatives, camalexin as well as cinnamic acid derivatives and other phenylpropanoids. These annotated metabolites indicate dynamic reprogramming of metabolic pathways that are functionally related towards creating an enhanced defensive capacity. The results reveal new insights into the mode of action of LPS as an activator of plant innate immunity, broadens knowledge about the defence metabolite pathways involved in Arabidopsis responses to LPS, and identifies specialised metabolites of functional importance that can be employed to enhance immunity against pathogen infection. PMID- 27656889 TI - A Genome-Wide Association Study of Attention Function in a Population-Based Sample of Children. AB - BACKGROUND: Attention function filters and selects behaviorally relevant information. This capacity is impaired in some psychiatric disorders and has been proposed as an endophenotype for Attention-Deficit/Hyperactivity Disorder; however, its genetic basis remains largely unknown. This study aimed to identify single nucleotide polymorphism (SNPs) associated with attention function. MATERIALS AND METHODS: The discovery sample included 1655 children (7-12 years) and the replication sample included 546 children (5-8 years). Five attention outcomes were assessed using the computerized Attentional Network Test (ANT): alerting, orienting, executive attention, Hit Reaction time (HRT) and the standard error of HRT (HRTSE). A Genome-wide Association Study was conducted for each outcome. Gene set enrichment analyses were performed to detect biological pathways associated with attention outcomes. Additional neuroimaging analyses were conducted to test neural effects of detected SNPs of interest. RESULTS: Thirteen loci showed suggestive evidence of association with attention function (P<10-5) in the discovery sample. One of them, the rs4321351 located in the PID1 gene, was nominally significant in the replication sample although it did not survive multiple testing correction. Neuroimaging analysis revealed a significant association between this SNP and brain structure and function involving the frontal-basal ganglia circuits. The mTOR signaling and Alzheimer disease-amyloid secretase pathways were significantly enriched for alerting, orienting and HRT respectively (FDR<5%). CONCLUSION: These results suggest for the first time the involvement of the PID1 gene, mTOR signaling and Alzheimer disease-amyloid secretase pathways, in attention function during childhood. These genes and pathways have been proposed to play a role in neuronal plasticity, memory and neurodegenerative disease. PMID- 27656892 TI - Transcriptome Profiling of the Pineapple under Low Temperature to Facilitate Its Breeding for Cold Tolerance. AB - The pineapple (Ananas comosus) is cold sensitive. Most cultivars are injured during winter periods, especially in sub-tropical regions. There is a lack of molecular information on the pineapple's response to cold stress. In this study, high-throughput transcriptome sequencing and gene expression analysis were performed on plantlets of a cold-tolerant genotype of the pineapple cultivar 'Shenwan' before and after cold treatment. A total of 1,186 candidate cold responsive genes were identified, and their credibility was confirmed by RT-qPCR. Gene set functional enrichment analysis indicated that genes related to cell wall properties, stomatal closure and ABA and ROS signal transduction play important roles in pineapple cold tolerance. In addition, a protein association network of CORs (cold responsive genes) was predicted, which could serve as an entry point to dissect the complex cold response network. Our study found a series of candidate genes and their association network, which will be helpful to cold stress response studies and pineapple breeding for cold tolerance. PMID- 27656893 TI - Breeding Value of Primary Synthetic Wheat Genotypes for Grain Yield. AB - To introduce new genetic diversity into the bread wheat gene pool from its progenitor, Aegilops tauschii (Coss.) Schmalh, 33 primary synthetic hexaploid wheat genotypes (SYN) were crossed to 20 spring bread wheat (BW) cultivars at the International Wheat and Maize Improvement Center. Modified single seed descent was used to develop 97 populations with 50 individuals per population using first back-cross, biparental, and three-way crosses. Individuals from each cross were selected for short stature, early heading, flowering and maturity, minimal lodging, and free threshing. Yield trials were conducted under irrigated, drought, and heat-stress conditions from 2011 to 2014 in Ciudad Obregon, Mexico. Genomic estimated breeding values (GEBVs) of parents and synthetic derived lines (SDLs) were estimated using a genomic best linear unbiased prediction (GBLUP) model with markers in each trial. In each environment, there were SDLs that had higher GEBVs than their recurrent BW parent for yield. The GEBVs of BW parents for yield ranged from -0.32 in heat to 1.40 in irrigated trials. The range of the SYN parent GEBVs for yield was from -2.69 in the irrigated to 0.26 in the heat trials and were mostly negative across environments. The contribution of the SYN parents to improved grain yield of the SDLs was highest under heat stress, with an average GEBV for the top 10% of the SDLs of 0.55 while the weighted average GEBV of their corresponding recurrent BW parents was 0.26. Using the pedigree based model, the accuracy of genomic prediction for yield was 0.42, 0.43, and 0.49 in the drought, heat and irrigated trials, respectively, while for the marker-based model these values were 0.43, 0.44, and 0.55. The SYN parents introduced novel diversity into the wheat gene pool. Higher GEBVs of progenies were due to introgression and retention of some positive alleles from SYN parents. PMID- 27656891 TI - Degradation Rate of 5-Fluorouracil in Metastatic Colorectal Cancer: A New Predictive Outcome Biomarker? AB - BACKGROUND: 5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC). Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FUDR) and genetic polymorphisms (MTHFR, TSER, DPYD) on survival. MATERIALS AND METHODS: Genetic polymorphisms of MTHFR, TSER and DPYD, and the 5-FUDR of homogenous patients with mCRC were retrospectively studied. Genetic markers and the 5-FUDR were correlated with clinical outcome. RESULTS: 133 patients affected by mCRC, treated with fluoropyrimidine-based chemotherapy from 2009 to 2014, were evaluated. Patients were classified into three metabolic classes, according to normal distribution of 5-FUDR in more than 1000 patients, as previously published: poor-metabolizer (PM) with 5-FU-DR <= 0,85 ng/ml/106 cells/min (8 pts); normal metabolizer with 0,85 < 5-FU-DR < 2,2 ng/ml/106 cells/min (119 pts); ultra-rapid metabolizer (UM) with 5-FU-DR >= 2,2 ng/ml/106 cells/min (6 pts). PM and UM groups showed a longer PFS respect to normal metabolizer group (14.5 and 11 months respectively vs 8 months; p = 0.029). A higher G3-4 toxicity rate was observed in PM and UM, respect to normal metabolizer (50% in both PM and UM vs 18%; p = 0.019). No significant associations between genes polymorphisms and outcomes or toxicities were observed. CONCLUSION: 5-FUDR seems to be significantly involved in predicting survival of patients who underwent 5-FU based CHT for mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes. PMID- 27656894 TI - MiRNA-Embedded ShRNAs for Radiation-Inducible LGMN Knockdown and the Antitumor Effects on Breast Cancer. AB - Legumain (LGMN) is highly expressed in breast cancer (BC) and other solid tumors and is a potential anticancer target. Here we investigate the anti-tumor effects of short hairpin RNAs (shRNAs) targeting LGMN embedded in a microRNA-155 (miR 155) architecture, which is driven by a radiation-inducible chimeric RNA polymerase II (Pol II) promoter. Lentiviral vectors were generated with the chimeric promoter which controlled the expression of downstream shRNA-miR-155 cassette. Fluorescence was observed by using confocal microscopy. Real-time quantitative PCR and Western blotting were used to determine the expression level of LGMN, MMP2, and MMP9. Furthermore, the proliferation and invasive ability of BC cells was analyzed via plate colony formation and invasion assays. Here we demonstrated that the chimeric promoter could be effectively induced by radiation treatment. Furthermore, the shRNA-miR-155 cassette targeting LGMN could be effectively activated by the chimeric promoter. Radiation plus knockdown of LGMN impairs colony formation and dampens cell migration and invasion in BC cells. Inhibition of LGMN downregulates MMP2 and MMP9 expression in BC cells. Pol II driven shRNA-miR-155 could effectively suppress the growth and invasiveness of BC cells, and that the interference effects could be regulated by radiation doses. Moreover, knockdown of LGMN alleviates the aggressive phenotype of BC cells through modulating MMPs expression. PMID- 27656895 TI - N-Terminal Lipid Modification Is Required for the Stable Accumulation of CyanoQ in Synechocystis sp. PCC 6803. AB - The CyanoQ protein has been demonstrated to be a component of cyanobacterial Photosystem II (PS II), but there exist a number of outstanding questions concerning its physical association with the complex. CyanoQ is a lipoprotein; upon cleavage of its transit peptide by Signal Peptidase II, which targets delivery of the mature protein to the thylakoid lumenal space, the N-terminal cysteinyl residue is lipid-modified. This modification appears to tether this otherwise soluble component to the thylakoid membrane. To probe the functional significance of the lipid anchor, mutants of the CyanoQ protein have been generated in Synechocystis sp. PCC 6803 to eliminate the N-terminal cysteinyl residue, preventing lipid modification. Substitution of the N-terminal cysteinyl residue with serine (Q-C22S) resulted in a decrease in the amount of detectable CyanoQ protein to 17% that of the wild-type protein. Moreover, the physical properties of the accumulated Q-C22S protein were consistent with altered processing of the CyanoQ precursor. The Q-C22S protein was shifted to a higher apparent molecular mass and partitioned in the hydrophobic phase in TX-114 phase partitioning experiments. These results suggest that the hydrophobic N-terminal 22 amino acids were not properly cleaved by a signal peptidase. Substitution of the entire CyanoQ transit peptide with the transit peptide of the soluble lumenal protein PsbO yielded the Q-SS mutant and resulted in no detectable accumulation of the modified CyanoQ protein. Finally, the CyanoQ protein was present at normal amounts in the PS II mutant strains DeltapsbB and DeltapsbO, indicating that an association with PS II was not a prerequisite for stable CyanoQ accumulation. Together these results indicate that CyanoQ accumulation in Synechocystis sp. PCC 6803 depends on the presence of the N-terminal lipid anchor, but not on the association of CyanoQ with the PS II complex. PMID- 27656897 TI - Correction: Assessing Progress, Impact, and Next Steps in Rolling Out Voluntary Medical Male Circumcision for HIV Prevention in 14 Priority Countries in Eastern and Southern Africa through 2014. AB - [This corrects the article DOI: 10.1371/journal.pone.0158767.]. PMID- 27656896 TI - Complement C3 Is the Strongest Predictor of Whole-Body Insulin Sensitivity in Psoriatic Arthritis. AB - OBJECTIVES: To evaluate the correlation between inflammatory measures and whole body insulin sensitivity in psoriatic arthritis (PsA) patients. METHODS: For the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT) was performed. The insulin sensitivity index (ISI), insulinogenic index (IGI) and oral disposition index (ODI) were calculated from dynamic values of glucose and insulin obtained during OGTT. RESULTS: In our study population, mean ISI was 3.5 +/- 2.5, median IGI was 1.2 (0.7-1.8), mean ODI 4.5 +/- 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP) (R = -0.52, p = 0.001), diastolic blood pressure (dBP) (R = -0.45, p = 0.004) and complement C3 (R = -0.43, p = 0.006) and ODI correlated inversely with sBP (R = -0.38, p = 0.02), dBP (R = -0.35, p = 0.03) and complement C3 (R = -0.37, p = 0.02). No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC) curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients. CONCLUSIONS: In conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients. PMID- 27656898 TI - The Dynamics of Platelet Activation during the Progression of Streptococcal Sepsis. AB - Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5, 12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection. PMID- 27656900 TI - Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus. AB - Barrett's esophagus (BE) is defined as metaplasia of the esophageal squamous epithelium with multiple cell layers into a single layer of intestinal columnar epithelial cells - or, in other words, skyscrapers are turned into town houses. The underlying pathomechanism(s) and the cell of origin of BE lesions have not been defined yet. However, four potential hypotheses for BE development have been suggested. The morphological changes during BE development are associated with rather well-described aberrant gene/protein expression patterns. However, the potential key regulators of this conversion process are still unclear. The process of metaplastic conversion is difficult to monitor in a spatiotemporal manner in vitro, and robust models are lacking. There is therefore a need for novel experimental systems. This review focuses on potential key regulators, microenvironmental influences, epigenetic alterations and experimental research systems related to BE. PMID- 27656899 TI - Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. AB - The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity. PMID- 27656901 TI - Simulating Ideal Assistive Devices to Reduce the Metabolic Cost of Running. AB - Tools have been used for millions of years to augment the capabilities of the human body, allowing us to accomplish tasks that would otherwise be difficult or impossible. Powered exoskeletons and other assistive devices are sophisticated modern tools that have restored bipedal locomotion in individuals with paraplegia and have endowed unimpaired individuals with superhuman strength. Despite these successes, designing assistive devices that reduce energy consumption during running remains a substantial challenge, in part because these devices disrupt the dynamics of a complex, finely tuned biological system. Furthermore, designers have hitherto relied primarily on experiments, which cannot report muscle-level energy consumption and are fraught with practical challenges. In this study, we use OpenSim to generate muscle-driven simulations of 10 human subjects running at 2 and 5 m/s. We then add ideal, massless assistive devices to our simulations and examine the predicted changes in muscle recruitment patterns and metabolic power consumption. Our simulations suggest that an assistive device should not necessarily apply the net joint moment generated by muscles during unassisted running, and an assistive device can reduce the activity of muscles that do not cross the assisted joint. Our results corroborate and suggest biomechanical explanations for similar effects observed by experimentalists, and can be used to form hypotheses for future experimental studies. The models, simulations, and software used in this study are freely available at simtk.org and can provide insight into assistive device design that complements experimental approaches. PMID- 27656902 TI - Sensing emotion in voices: Negativity bias and gender differences in a validation study of the Oxford Vocal ('OxVoc') sounds database. AB - Emotional expressions are an essential element of human interactions. Recent work has increasingly recognized that emotional vocalizations can color and shape interactions between individuals. Here we present data on the psychometric properties of a recently developed database of authentic nonlinguistic emotional vocalizations from human adults and infants (the Oxford Vocal 'OxVoc' Sounds Database; Parsons, Young, Craske, Stein, & Kringelbach, 2014). In a large sample (n = 562), we demonstrate that adults can reliably categorize these sounds (as 'positive,' 'negative,' or 'sounds with no emotion'), and rate valence in these sounds consistently over time. In an extended sample (n = 945, including the initial n = 562), we also investigated a number of individual difference factors in relation to valence ratings of these vocalizations. Results demonstrated small but significant effects of (a) symptoms of depression and anxiety with more negative ratings of adult neutral vocalizations (R2 = .011 and R2 = .008, respectively) and (b) gender differences in perceived valence such that female listeners rated adult neutral vocalizations more positively and infant cry vocalizations more negatively than male listeners (R2 = .021, R2 = .010, respectively). Of note, we did not find evidence of negativity bias among other affective vocalizations or gender differences in perceived valence of adult laughter, adult cries, infant laughter, or infant neutral vocalizations. Together, these findings largely converge with factors previously shown to impact processing of emotional facial expressions, suggesting a modality-independent impact of depression, anxiety, and listener gender, particularly among vocalizations with more ambiguous valence. (PsycINFO Database Record PMID- 27656903 TI - Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence. AB - Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila. PMID- 27656906 TI - The Parent Li(OH)FeSe Phase of Lithium Iron Hydroxide Selenide Superconductors. AB - Lithiation of hydrothermally synthesized Li1-xFex(OH)Fe1-ySe turns on high temperature superconductivity when iron ions are displaced from the hydroxide layers by reductive lithiation to fill the vacancies in the iron selenide layers. Further lithiation results in reductive iron extrusion from the hydroxide layers, which turns off superconductivity again as the stoichiometric composition Li(OH)FeSe is approached. The results demonstrate the twin requirements of stoichiometric FeSe layers and reduction of Fe below the +2 oxidation state as found in several iron selenide superconductors. PMID- 27656907 TI - Exploring the Scope of Asymmetric Synthesis of beta-Hydroxy-gamma-lactams via Noyori-type Reductions. AB - Enantio- and diastereoselective hydrogenation of beta-keto-gamma-lactams with a ruthenium-BINAP catalyst, involving dynamic kinetic resolution, has been employed to provide a general, asymmetric approach to beta-hydroxy-gamma-lactams, a structural motif common to several bioactive compounds. Full conversion to the desired beta-hydroxy-gamma-lactams was achieved with high diastereoselectivity (up to >98% de) by addition of catalytic HCl and LiCl, while beta-branching of the ketone substituent demonstrated a pronounced effect on the modest to excellent enantioselectivity (up to 97% ee) obtained. PMID- 27656904 TI - Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in Drosophila. AB - Ionotropic Receptors (IRs) are a large subfamily of variant ionotropic glutamate receptors present across Protostomia. While these receptors are most extensively studied for their roles in chemosensory detection, recent work has implicated two family members, IR21a and IR25a, in thermosensation in Drosophila. Here we characterize one of the most evolutionarily deeply conserved receptors, IR93a, and show that it is co-expressed and functions with IR21a and IR25a to mediate physiological and behavioral responses to cool temperatures. IR93a is also co expressed with IR25a and a distinct receptor, IR40a, in a discrete population of sensory neurons in the sacculus, a multi-chambered pocket within the antenna. We demonstrate that this combination of receptors is required for neuronal responses to dry air and behavioral discrimination of humidity differences. Our results identify IR93a as a common component of molecularly and cellularly distinct IR pathways important for thermosensation and hygrosensation in insects. PMID- 27656908 TI - Comparison of Solvation Effects on CO2 Capture with Aqueous Amine Solutions and Amine-Functionalized Ionic Liquids. AB - Amines are the most widely utilized chemicals for postcombustion CO2 capture, because the reversible reactions between amines and CO2 through their moderate interaction allow effective "catch and release". Usually, CO2 is dissolved in the form of an anion such as carbamate or bicarbonate. Therefore, the reaction energy diagram is potentially governed to a large extent by the polarity of the surrounding solvent. Herein, we compared aqueous amine solutions and amine functionalized ionic liquids by investigating their dielectric constants and performing an intrinsic reaction coordinate analysis of the CO2 absorption process. Quantum mechanical calculations at the CCSD(T)/6-311++G(d,p)//B3LYP/6 311++G(d,p) level within the continuum solvation model (SMD/IEF-PCM) revealed contrasting dependencies of C-N bond formation on the dielectric constant in those solutions. Amines react with CO2 on an energy surface that is significantly affected by the dielectric constant in conventional aqueous amine solutions, whereas amine-functionalized anions and CO2 form stable C-N bonds with a comparatively lower activation energy regardless of the dielectric constant. PMID- 27656905 TI - The ubiquitin-proteasome system regulates focal adhesions at the leading edge of migrating cells. AB - Cell migration requires the cyclical assembly and disassembly of focal adhesions. Adhesion induces phosphorylation of focal adhesion proteins, including Cas (Crk associated substrate/p130Cas/BCAR1). However, Cas phosphorylation stimulates adhesion turnover. This raises the question of how adhesion assembly occurs against opposition from phospho-Cas. Here we show that suppressor of cytokine signaling 6 (SOCS6) and Cullin 5, two components of the CRL5SOCS6 ubiquitin ligase, inhibit Cas-dependent focal adhesion turnover at the front but not rear of migrating epithelial cells. The front focal adhesions contain phospho-Cas which recruits SOCS6. If SOCS6 cannot access focal adhesions, or if cullins or the proteasome are inhibited, adhesion disassembly is stimulated. This suggests that the localized targeting of phospho-Cas within adhesions by CRL5SOCS6 and concurrent cullin and proteasome activity provide a negative feedback loop, ensuring that adhesion assembly predominates over disassembly at the leading edge. By this mechanism, ubiquitination provides a new level of spatio-temporal control over cell migration. PMID- 27656909 TI - Combining Immune Checkpoint Inhibitors and Kinase-Inhibiting Supramolecular Therapeutics for Enhanced Anticancer Efficacy. AB - A major limitation of immune checkpoint inhibitors is that only a small subset of patients achieve durable clinical responses. This necessitates the development of combinatorial regimens with immunotherapy. However, some combinations, such as MEK- or PI3K-inhibitors with a PD1-PDL1 checkpoint inhibitor, are pharmacologically challenging to implement. We rationalized that such combinations can be enabled using nanoscale supramolecular targeted therapeutics, which spatially home into tumors and exert temporally sustained inhibition of the target. Here we describe two case studies where nanoscale MEK- and PI3K-targeting supramolecular therapeutics were engineered using a quantum mechanical all atomistic simulation-based approach. The combinations of nanoscale MEK- and PI3K targeting supramolecular therapeutics with checkpoint PDL1 and PD1 inhibitors exert enhanced antitumor outcome in melanoma and breast cancers in vivo, respectively. Additionally, the temporal sequence of administration impacts the outcome. The combination of supramolecular therapeutics and immunotherapy could emerge as a paradigm shift in the treatment of cancer. PMID- 27656910 TI - Sequential Thiol-Ene and Tetrazine Click Reactions for the Polymerization and Functionalization of Hydrogel Microparticles. AB - Click chemistry is a versatile tool for the synthesis and functionalization of polymeric biomaterials. Here, we describe a versatile new strategy for producing bioactive, protein-functionalized poly(ethylene glycol) (PEG) hydrogel microparticles that is based on sequential thiol-ene and tetrazine click reactions. Briefly, tetra-functional PEG-norbornene macromer and dithiothreitol (SH) cross-linker were combined at a 0.75:1 [SH]:[norbornene] ratio, emulsified in a continuous Dextran phase, and then photopolymerized to form PEG hydrogel microparticles that varied from 8 to 30 MUm in diameter, depending on the PEG concentration used. Subsequently, tetrazine-functionalized protein was conjugated to unreacted norbornene groups in the PEG microparticles. Tetrazine-mediated protein tethering to the microparticles was first demonstrated using fluorescein labeled ovalbumin as a model protein. Subsequently, bioactive protein tethering was demonstrated using alkaline phosphatase (ALP) and glucose oxidase (GOx). Enzyme activity assays demonstrated that both ALP and GOx maintained their bioactivity and imparted tunable bioactivity to the microparticles that depended on the amount of enzyme added. ALP-functionalized microparticles were also observed to initiate calcium phosphate mineralization in vitro when incubated with calcium glycerophosphate. Collectively, these results show that protein functionalized hydrogel microparticles with tunable bioactive properties can be easily synthesized using sequential click chemistry reactions. This approach has potential for future applications in tissue engineering, drug delivery, and biosensing. PMID- 27656912 TI - Geometric Complementarity in Assembly and Guest Recognition of a Bent Heteroleptic cis-[Pd2LA2LB2] Coordination Cage. AB - Due to the inherent difficulties in achieving a defined and exclusive formation of multicomponent assemblies against entropic predisposition, we present the rational assembly of a heteroleptic [Pd2LA2LB2]4+ coordination cage achieved through the geometric complementarity of two carefully designed ligands, LA and LB. With Pd(II) cations as rigid nodes, the pure distinctly angular components readily form homoleptic cages, a [Pd2LA4]4+ strained helical assembly and a [Pd4LB8]8+ box-like structure, both of which were characterized by X-ray analysis. Combined, however, the two ligands could be used to cleanly assemble a cis-[Pd2LA2LB2]4+ cage with a bent architecture. The same self-sorted product was also obtained by a quantitative cage-to-cage transformation upon mixing of the two homoleptic cages revealing the [Pd2LA2LB2]4+ assembly as the thermodynamic minimum. The structure of the heteroleptic cage was examined by ESI-MS, COSY, DOSY, and NOESY methods, the latter of which pointed toward a cis-conformation of ligands in the assembly. Indeed, DFT calculations revealed that the angular ligands and strict Pd(II) geometry strongly favor the cis-[Pd2LA2LB2]4+ species. The robust nature of the cis-[Pd2LA2LB2]4+ cage allowed us to probe the accessibility of its cavity, which could be utilized for shape recognition toward stereoisomeric guests. The ability to directly combine two different backbones in a controlled manner provides a powerful strategy for increasing complexity in the family of [Pd2L4] cages and opens up possibilities of introducing multiple functionalities into a single self-assembled architecture. PMID- 27656911 TI - Palonosetron-5-HT3 Receptor Interactions As Shown by a Binding Protein Cocrystal Structure. AB - Palonosetron is a potent 5-HT3 receptor antagonist and an effective therapeutic agent against emesis. Here we identify the molecular determinants of compound recognition in the receptor binding site by obtaining a high resolution structure of palonosetron bound to an engineered acetylcholine binding protein that mimics the 5-HT3 receptor binding site, termed 5-HTBP, and by examining the potency of palonosetron in a range of 5-HT3 receptors with mutated binding site residues. The structural data indicate that palonosetron forms a tight and effective wedge in the binding pocket, made possible by its rigid tricyclic ring structure and its interactions with binding site residues; it adopts a binding pose that is distinct from the related antiemetics granisetron and tropisetron. The functional data show many residues previously shown to interact with agonists and antagonists in the binding site are important for palonosetron binding, and indicate those of particular importance are W183 (a cation-pi interaction and a hydrogen bond) and Y153 (a hydrogen bond). This information, and the availability of the structure of palonosetron bound to 5-HTBP, should aid the development of novel and more efficacious drugs that act via 5-HT3 receptors. PMID- 27656913 TI - Formal Total Synthesis of Amphidinolide Q. AB - With the preparation of macrolactone 33a we describe a formal total synthesis of amphidinolide Q. The corresponding seco acid 32 originated from an aldol reaction between methyl ketone 6 and methyl (E)-3-methyl-4-oxobut-2-enoate (5). The synthesis of ketone 6 (C5-C16 fragment) started with desymmetrized meso-diol 9. Chain extension reactions involving cyanide, lithium trimethylsilylacetylide, and a Wittig reaction led to aldehyde 22. The two additional stereocenters at C11 and C13 were set by a Noyori transfer hydrogenation on alkynone 14 and a Feringa Minnaard methyl cuprate addition on enoate 21. The but-1-ene-2-yl subunit on the side chain terminus was created from an unsaturated aldehyde by a substitution reaction on a derived allylic tosylate. PMID- 27656914 TI - Falls and Fall Injuries Among Adults Aged >=65 Years - United States, 2014. AB - Falls are the leading cause of fatal and nonfatal injuries among adults aged >=65 years (older adults). During 2014, approximately 27,000 older adults died because of falls; 2.8 million were treated in emergency departments for fall-related injuries, and approximately 800,000 of these patients were subsequently hospitalized.* To estimate the numbers, percentages, and rates of falls and fall injuries among older adults by selected characteristics and state, CDC analyzed data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) survey. In 2014, 28.7% of older adults reported falling; the estimated 29.0 million falls resulted in 7.0 million injuries. Known effective strategies for reducing the number of older adult falls include a multifactorial clinical approach (e.g., gait and balance assessment, strength and balance exercises, and medication review). Health care providers can play an important role in fall prevention by screening older adults for fall risk, reviewing and managing medications linked to falls, and recommending vitamin D supplements to improve bone, muscle, and nerve health and reduce the risk for falls. PMID- 27656915 TI - Effect of Adjunctive Aripiprazole on Sexual Dysfunction in Schizophrenia: A Preliminary Open-Label Study. AB - Introduction: Although adjunctive aripiprazole improves hyperprolactinemia, sufficient evidence for its effects on sexual dysfunction has not been obtained. We assessed the usefulness of adjunctive aripiprazole for schizophrenia with sexual dysfunction. Methods: 22 Japanese schizophrenia patients with antipsychotic-induced hyperprolactinemia and sexual dysfunction were enrolled, and 19 of them completed the study. Aripiprazole was administrated in a flexible titration schedule to participants according to the judgment of each doctor, and patients were followed for 24 weeks. Serum prolactin, Clinical Global Impression Scales-Severity (CGI-S), and Nagoya Sexual Function Questionnaire (NSFQ) were measured at baseline and at 4, 8, 12, and 24 weeks. Results: Prolactin at week 4 and later was significantly lower than that at baseline. Compared to baseline, we observed a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later. In males, erectile dysfunction was significantly reduced at week 24. In females, menstrual irregularity and galactorrhea were significantly reduced at week 24. CGI-S did not significantly change. Discussion: Although the small sample size is a limitation in this study, adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia. PMID- 27656916 TI - [Health and quality of life in the elderly]. PMID- 27656917 TI - [The need to share and disseminate health-related scientific publications regarding the general population]. PMID- 27656918 TI - [Institutional differences in the ineffective access to prescription medication in health care centers in Peru: analysis of the National Survey on User Satisfaction of Health Services (ENSUSALUD 2014)]. AB - Objectives To estimate the prevalence of ineffective access to drugs (IAD) and associated factors in patients receiving a prescription in an outpatient clinic in Peru. Materials and Methods We performed a secondary data-analysis of the National Survey on User Satisfaction of Health Services (ENSUSALUD 2014), a two stage population-based study carried out in health care centers of the Ministry of Health and Regional Governments (MOHRG), Social Security (EsSalud), Armed Forces and Police (AFP) and the private sector across all 25 regions of Peru. IAD was defined as incomplete or no dispensing of any prescribed medication in the health care center pharmacy. Generalized linear models with Poisson distribution for complex survey sampling were fit to estimate prevalence ratios (PR) and 95% confidence intervals (CI). Results Out of 13,360 participants, 80.9 % (95% CI: 79.9-81.8) had an active prescription, and of those, 90.8 % (95% CI: 90.1-91.6) sought their medications in a health care center pharmacy, where 30.6 % (95% CI 28.8-32.4) had IAD. In the multiple regression model, receiving medical attention in the MOHRG (PR 4.8; 95%CI: 3.5-6.54) or AFP (PR: 3.2; 95%CI: 2.3-4.5), being over 60 years old (PR: 1.17; 95%CI: 1.04-1.34) and being in the poorest income quintile (PR: 1.05; 95%CI: 1.05-1.41) increased IAD. Furthermore, in contrast to seeking care for pregnancy or other routine control, IAD was also more common for medical consultation for diseases diagnosed in the last 15 days (PR: 1.37; 95% CI: 1.05-1.79) or more than 15 days prior (PR: 1.51; 95% CI: 1.16-1.97). Conclusions In Peru, IAD is associated with the provider institution, older age, poverty and the reason for medical consultation. We suggest strategies to promote access to medicines, especially in the most disadvantaged segments of the Peruvian population. PMID- 27656919 TI - [Prevalence of purchase of antibiotics without prescription and antibiotic recommendation practices for children under five years of age in private pharmacies in peri-urban areas of Lima, Peru]. AB - OBJECTIVES: To determine the prevalence of purchase of antibiotics without prescription and antibiotic recommendation for its use in children <5 years of age in private pharmacies in peri-urban areas of Lima. MATERIALS AND METHODS: An anonymous population survey was conducted among adults who bought an antibiotic for a child <5 years of age from a private pharmacy. Fictitious cases were applied in a subgroup of pharmacies to evaluate antibiotic recommendation practices. RESULTS: The prevalence of purchase of antibiotics without a prescription was 13%, including 1.7% that were chosen by consumers and 11.3% that were recommended by pharmacists. A total of 66.7% of the medications purchased to treat colds were antibiotics, 56.9% of which were prescribed. 64.4% of medications purchased to treat bronchospasm, 96.4% of the medications to treat watery diarrhea and 90.9% of the medications to treat pharyngitis were antibiotics. Amoxicillin (51.5%) and trimethoprim-sulfamethoxazole (20.6%) were the most commonly purchased antibiotics. A pharmacist suggested an antibiotic in 60% of the fictitious common cold cases, 76% of the bronchospasm cases, 44% of the watery diarrhea cases, and 76% of the dysentery cases. CONCLUSIONS: The purchase of antibiotics for children <5 years of age in private pharmacies primarily occurs with a medical prescription. The pharmacist commonly recommended an antibiotic in cases lacking a prescription. Measures are needed to reduce the inappropriate use of antibiotics at medical facilities and in pharmacies. PMID- 27656920 TI - [Factors associated with fulfillment of growth and development monitoring for children <1 year of age in health centers in Amazonas, Loreto and Pasco]. AB - OBJECTIVES: To identify the factors associated with growth and development monitoring (CRED) fulfillment for children <1 year in Ministry of Health (MINSA) health centers in Amazonas, Loreto, and Pasco, Peru between January and December 2012. MATERIALS AND METHODS: A paired case-control study was performed. A case was the child who did not complete 11 of the CRED checks until the age of 11 months and, as a control, that child with 11 CRED checks with the same age. The correlation among factors with CRED fulfillment was determined using the McNemar test (p < 0.05) and odds ratio (OR) was used to determine the strength of the associations for paired samples (95% confidence interval [CI]). RESULTS: After the control of various variables, seven factors had significant association with CRED monitoring fulfillment. The common factor in the three regions studied was that the child were not attended some time, which was associated, three to five times, with the chance of not fulfilling the CRED checks in Loreto and Pasco; in Amazonas, the opposite effect was observed (OR, 0.58; 95% CI, 0.41-0.81). CONCLUSIONS: The factors related to CRED fulfillment in children <1 year of age varied among regions. One of the main identified obstacles is the multiple functions that must be performed by professionals working in CRED, owing to which, child care opportunities are lost. Hence, adequate staffing must be ensured while instilling ever-present proper patient treatment. PMID- 27656921 TI - [Estimation of economic costs for the care of patients with nosocomial pneumonia in a regional peruvian hospital, 2009-2011]. AB - OBJECTIVES: To estimate and compare the economic costs for the care of patients with and without nosocomial pneumonia at Hospital II Huanuco EsSalud during 2009 2011, in Peru. MATERIALS AND METHODS: This was a partial economic evaluation of paired cases and controls. A collection sheet was used. DEPENDENT VARIABLE: nosocomial pneumonia. INDEPENDENT VARIABLES: direct health costs, direct non health costs, indirect costs, occupation, age, comorbidities, sex, origin, and education level. A bivariate analysis was performed. RESULTS: Forty pairs of cases and controls were identified. These patients were hospitalized for >2 weeks and prescribed more than two antibiotics. The associated direct health costs included those for hospitalization, antibiotics, auxiliary examinations, specialized assessments, and other medications. The direct non-health costs and associated indirect costs included those for transportation, food, housing, foregone payroll revenue, foregone professional fee revenue, extra-institutional expenses, and payment to caregivers during hospitalization and by telephone. CONCLUSIONS: The direct health costs for nosocomial pneumonia patients were more than three times and the indirect costs were more than two times higher than those for the controls. Variables with the greatest impact on costs were identified. PMID- 27656922 TI - [Prevalence of burnout syndrome in peruvian physicians and nurses, ENSUSALUD 2014]. AB - Objectives To estimate the prevalence of burnout syndrome (BOS) in Peruvian physicians and nurses in 2014 according to different cutoff points established in the literature. Materials and methods This was a cross-sectional and descriptive study based on the National Survey on User Satisfaction of Health Services for 2014 (ENSUSALUD-2014), which features two-stage probability sampling. BOS was identified by the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) using different cutoff points to establish prevalence, including default values, terciles, and quartiles. Results Of the 5062 health professionals, 62.3% were women, 44.0% were physicians, 46.0% belonged to the MINSA, and 23.1% worked in Lima. The overall BOS prevalence was 2.8% (95% CI, 2.4-3.2), when default values were used; the prevalence was 7.9% (95% CI, 7.3-8.6) when quartiles were used as cutoff points and 12.5% (95% CI, 11.4-13.6) when terciles were used as cutoff points. The prevalence was higher in doctors than in nurses, regardless of the cutoff point used (3.7% vs. 2.1% using default values, 10.2 vs. 6.1% using quartiles, and 16.2 vs. 9.5% using terciles). Conclusions The prevalence of BOS in health workers differs within the same population when different cutoff points are used. The use of default values is recommended by the instrument author until specific cut-points for our country are obtained. PMID- 27656923 TI - [Risk factors for arterial hypertension in the adult population of an urban region of Ecuador]. AB - Objectives . To determine the risk factors for arterial hypertension (HTN) in the adult resident population of the city of Cuenca, Ecuador Materials and methods A cross-sectional analytical study of adults selected via multistage random sampling who underwent clinical, anthropometric, and laboratory evaluations. The diagnosis of HTN was defined according to the JNC-7 criteria. A multiple logistic regression model was performed Results A total of 318 persons were included. The prevalence of HTN was 25.8% (males: 27.2% vs. females: 24.7%; p = 0.617). In the multiple logistic regression model, the risk factors for HTN were age > 60 years (OR, 8.68; 95% CI, 3.56-21.14; p < 0.001), obesity according to body mass index (OR, 2.36; 95% CI, 1.04-5.70; p = 0.042), high caloric intake (OR, 2.06; 95% CI, 1.01- 4.53; p = 0.044), and family history of HTN (OR, 1.58; 95% CI, 1.02-2.90; p = 0.040) Conclusions The presence of HTN in this population is associated with both intrinsic and environmental factors, which should be considered in routine evaluations to ensure its early identification and control. PMID- 27656924 TI - [Comparative genomic analysis of peruvian strains of Mycobacterium tuberculosis]. AB - OBJECTIVES: To comparatively analyze three genomic sequences of Mycobacterium tuberculosis(MTB), including sensitive (INS-SEN), multi-drug-resistant (INS-MDR), and extremely drug-resistant (INS-XDR) strains, collected in Lima, Peru. MATERIALS AND METHODS: Specific single nucleotide polymorphisms (SNPs) were identified in the INS SEN, INS-MDR, and INS-XDR strains according to the inclusion/exclusion criteria. The three MTB genomes were compared and a molecular phylogeny was constructed with 27 MTB strains from other studies available from the Genbank database. RESULTS: The specific SNPs in each genome were organized in clusters of orthologous groups (COGs). The genomic analysis allowed for the identification of a set of SNPs associated mainly with virulence determinants (family of mce proteins, polyketides, phiRv1, transposase, and methyltransferases, and other related to vitamin synthesis). A close correlation between the INS-MDR and INS-XDR strains was observed, with only a 6.1% difference in SNPs; however, the INS-SEN strain had 50.2% and 50.3% different SNPs from the MDR and XDR strains, respectively. The molecular phylogeny grouped the Peruvian strains within the LAM lineage and closely to the F11 and KZN strains from South Africa. CONCLUSIONS: High similarity (99.9%) was noted between the INS-SEN strain and the F11 South African strain with broadglobal scope, while the analysis of the INS-MDR and INS-XDR strains showed a likely expansion of the KZN family, a South African strain with high virulence and pathogenicity. PMID- 27656925 TI - [Fewer hours of sleep associated with increased body weight in chilean university nutrition students]. AB - The aim of the study was to determine the association between fewer hours of sleep and excess weight/obesity in first- to fourth-year nutrition students at Universidad de San Sebastian in Chile. A total of 635 students were evaluated, of whom 86.4% were women. The Pittsburg sleep survey was administered to each student along with an anthropometric evaluation, and the body mass index of each was calculated. A raw and adjusted analysis of logistic regression was performed. A total of 57.1% of students slept less than the recommended amount. Sleeping less was associated with excess weight or obesity in the model adjusted for age and daytime sleepiness (adjusted OR [aOR], 1.84; 95% CI, 1.26-2.68), and adjusted for age, smoking, dairy, fruit, and legume consumption; and daytime sleepiness (aOR, 1.83; 95% CI, 1.29-2.76). There is an association between fewer hours of sleep and higher body mass in this population; this should be considered in excess weight prevention. PMID- 27656926 TI - [Cloning alphavirus and flavivirus sequences for use as positive controls in molecular diagnostics]. AB - The purpose of the study was to obtain a positive control to validate molecular techniques (reverse transcription- polymerase chain reaction [RT-PCR]) used in the diagnosis and research of viral infections. From strains of Chikungunya virus (CHIKV), Zika virus, and Dengue virus (DENV-1, DENV-2, DENV- 3, and DENV-4) viral RNAs were extracted to obtain complementary DNA using RT-PCR from the nsP4 (CHIKV), NS5 (Zika virus), C/prM-M, and 5'UTR-C (DENV-1, DENV-2, DENV-3, DENV-4) sequences, which were cloned into pGEM(r)-T Easy. Cloning was confirmed through colony PCR, from which plasmid DNA was extracted for fragment cloning verification. Cloning of cDNA corresponding to nsP4, NS5, C/prM-M, and 5'UTR-C of the different viral agents was achieved. In conclusion, recombinant plasmids were obtained with each of the sequences specified for further assessment as positive controls in molecular techniques in an effort to avoid the use of cell cultures, which can be costly, time-consuming, and potentially dangerous. PMID- 27656927 TI - [Carbon footprint in five third-level health care centers in Peru, 2013]. AB - This study was performed to calculate the carbon footprint generated by third level health care centers located in Lima, Peru, in 2013. Reports were obtained on the consumption of energy resources and water as well as on waste generation from the five centers, which contributed to climate change with an emission of 14,462 teq of CO2. A total of 46% of these emissions were associated with fuel consumption by the powerhouse, power generators, and transport vehicles; 44% was related to energy consumption; and the remaining 10% was related to the use of water and generation of solid hospital waste. CO2, N2O, and CH4 are the greenhouse gases included in the estimated carbon footprint. Our results show that hospitals have a negative environmental impact, mainly due to fossil fuel consumption. PMID- 27656928 TI - [Use of lumbar puncture in the evaluation of late-onset sepsis in low birth weight neonates]. AB - The objective of this study was to analyze the use of lumbar punctures (LP) in the evaluation of late-onset neonatal sepsis. It is recommended to perform an LP as part of the evaluation of late-onset sepsis. We used a cohort of 414 newborns with a birth weight <2000g in three hospitals in Lima. A LP was performed in 45/214 (21.0%) of sepsis evaluations and in 13/48 (27.1%) of culture-proven sepsis. Meningitis was diagnosed in 8/214 (3.7%) of the episodes and 8/45 (17.5%) of the evaluations that included an LP. The duration of treatment of the sepsis episodes without a LP and the episodes with a negative LP was similar, and shorter than the episodes with a positive LP. The use of LP in the evaluation of late-onset sepsis is low and can result in undiagnosed and undertreated meningitis. The use of LP in the evaluation of neonatal sepsis must be encouraged in the neonatal units. PMID- 27656929 TI - [Behaviors in response to the tuberculin skin test conversion in medical students from a university in Lima, Peru]. AB - The aim of this study was to determine the behaviors in response to tuberculin skin test (PPD) conversion and the reasons for starting or not starting treatment for latent tuberculosis infection (TILT) among medical students at a university in Lima, Peru. A total of 548 participants completed a questionnaire; of them, 6.7% tested positive on university admission and 11.1% were recent converters. A total of 55.7% did not start TILT and had no explanation. Of the recent converters, most students who did start TILT were >22 years old (p = 0.01) and correctly answered general knowledge questions (p = 0.04). It is important to note that the PPD conversion rate was higher than that reported in the literature and that most students did not follow the treatment prophylaxis because of a lack of information. PMID- 27656930 TI - [The 1, 2, 3 of laboratory animal experimentation]. AB - The slow scientific development in Latin America in recent decades has delayed the incorporation of laboratory animal experimentation; however, this situation has started to change. Today, extraordinary scientific progress is evident, which has promoted the introduction and increased use of laboratory animals as an important tool for the advancement of biomedical sciences. In the aftermath of this boom, the need to provide the scientific community with training and guidance in all aspects related to animal experimentation has arisen. It is the responsibility of each country to regulate this practice, for both bioethical and legal reasons, to ensure consideration of the animals' rights and welfare. The following manuscript is the result of papers presented at the International Workshop on Laboratory Animal Testing held at the Technical University of Ambato, Ecuador; it contains information regarding the current state of affairs in laboratory animal testing and emphasizes critical aspects such as main species used, ethical and legal principles, and experimental and alternative designs for animal use. These works aim to ensure good practices that should define scientific work. This document will be relevant to both researchers who aim to newly incorporate animal testing into their research and those who seek to update their knowledge. PMID- 27656931 TI - [El nino phenomenon and natural disasters: public health interventions for disaster preparedness and response]. AB - This article reviews public health interventions for preparedness and response to natural disasters within the context of El Nino phenomenon using systematic reviews and a review of revisions with emphasis on vector-borne diseases, water borne diseases, malnutrition, heat stress, drought, flood-associated diseases, mental health problems, vulnerability of the physical health-system infrastructure, as well as long-term policies aimed at protecting the populations of these cases. Environmental interventions were identified, including vector control, chemoprophylaxis, immunization, and intradomiciliary water treatment. While these finds are based primarily on systematic reviews, it is necessary to evaluate the benefit of these interventions within the population, according to the context of each region. PMID- 27656932 TI - [Health promotion and disease prevention for active aging that preserves quality of life]. AB - Older adults represent a growing population whose health status depends on many factors, including physical, cognitive, and social factors, as well as family. They also have features including heterogeneity, a high disease burden, and comorbidities that affect the family and social spheres. It is important to offer the older adult population methods to exercise better control over their health and, thus, improve it. The goal is to achieve successful aging, that is, aging without disabilities, with the fewest possible or adequately controlled ailments while helping them maintain their autonomy and quality of life and always respecting their values and preferences. On the other hand, preventive activities in older adults consider the risk of disease; functional alteration causing the disease; and conditions common to the elderly that can damage their health, including frailty, falls, and iatrogenic complications. Preventive activities for the elderly should consider all of these factors. Here we present some guidelines that may be important for promoting active aging as well as preventive activities that can be used according to each person's individual situation. PMID- 27656933 TI - [Usefulness of the comprehensive geriatric assessment for evaluating the health of older adults]. AB - Older adults comprise a heterogeneous population group that usually has a high disease burden, comorbidities, and, in many cases, subclinical conditions that compromise their health and quality of life. In addition to the physical component, the health conditions of elderly individuals are significantly influenced by cognitive and affective components, social and family factors such as abandonment, and functional factors including the ability to perform everyday activities. In response to this complex scenario, the comprehensive geriatric evaluation constitutes a multidimensional and interdisciplinary diagnostic tool that assesses the health of older adults in all of its complexity by considering the physical, mental, social/family, and functional needs to obtain full knowledge of older person's health status and creating a plan that consists of appropriate and individualized interventions that considers the preferences and values of older individuals and their families. PMID- 27656934 TI - [Frailty in older adults: detection, community-based intervention, and decision making in the management of chronic illnesses]. AB - Physical fragility is defined as "a medical syndrome with multiple causes and factors that contribute to its development and that is characterized by decreased strength and resistance as well as reduced physiological functioning, which increase an individual's vulnerability to functional dependence or death." Different multi-systemic pathophysiological processes are involved in the pathogenesis of frailty syndrome, one of the most important being the loss of muscle mass associated with aging or sarcopenia. Several studies have demonstrated that physical frailty increases with age. Physical exercise is the best form of intervention for preventing and treating frailty. In older adults with chronic illnesses, identifying frailty is very important for decision making, individualizing management, and considering their values and care preferences. PMID- 27656935 TI - [Strategies to optimize pharmacological management in older adults]. AB - Population aging increases the prevalence of chronic and multiple morbid illnesses and increases the consumption of multiple medications and related problems accordingly. It is reported that >50% of dispensed medications are consumed by older adults; in fact, >80% of older adults take at least one medication daily and 75% do not inform their doctor that they are using unconventional treatments. Appropriate medication prescription to older adults is challenging and it requires the consideration of risks and benefits of the indicated medications, for which clear evidence of their efficacy is often lacking due to the limited inclusion of elderly populations in randomized clinical trials on which clinical guides are based for chronic disease management. However, general guidelines and recommendations must be comprehensively implemented and supported by a multidisciplinary team whenever pharmacological management is provided for older adults. Here we focus on promoting proper prescriptions according to evidence-based recommendations to reduce inappropriate prescriptions, polypharmacy, and self-medication. PMID- 27656936 TI - [Mental health in older adults: major neurocognitive, affective, and sleep disorders]. AB - Numerous biological, psychological, and social factors influence the mental health of elderly individuals to varying degrees. Apart from components related to the normal aging process and the co-occurrence of various medical conditions, events such as the death of a loved one, retirement, or disability significantly contribute to a variety of mental and emotional problems in this stage of the life cycle. The most frequent problems affect the neurocognitive, emotional, and oneiric spheres. Major neurocognitive disorders reduce one's overall performance and, thus, increase their need for close care. Affective disorders may be exacerbated by the lack of family support and decreased social interactions, which may lead to significant isolation result in suicidal behavior. The increased frequency of sleep disorders such as insomnia and daytime sleepiness and specific disorders such as obstructive apnea significantly alter the quality of life of this population. PMID- 27656937 TI - [Social health care for older adults in Peru]. AB - Demographic and epidemiological changes have led to restructuring of the local and global health systems, changes that focus on broader coverage in which importance is given to an individual's physical well-being as well as social welfare in an effort to ensure healthy aging. In this review, the current social health care approach is analyzed from the different institutions that care for older populations and the changes that have resulted from boarding and caring for older adults. PMID- 27656938 TI - [New rules for medical residency qualification in Peru: problems and perspectives]. AB - On May 11, 2015, amendment RS 017-2015-SA to the Regulation of the National System of Medical Residency (RS 002-2006-SA) was published in the Peruvian official newspaper "El Peruano". This amendment establishes that the submission of a thesis or scholarly work is not necessary to obtain the title of medical specialist (article 28), but when a "work project" is performed in a specialty area, it must be presented at the conclusion of the second year of medical residency (article 27). This news has been welcomed by one sector of medical residents, while others believe that the measure conflicts with their training as specialists. This article aims to analyze the new rules for medical residency qualification in Peru and its implications for research developed during this formative stage for specialist physicians. PMID- 27656939 TI - [Citizen security observatories: tools for decision making and governability]. AB - The need for good governability to promote countries development has been becoming the focus of governments. Latin America has political systems in crisis of governability caused by the inability of strategic actors to solve conflicts based on rules and procedures. The present review aims to describe how the creation of violence surveillance systems (observatories) contributes to strengthening governability and the creation of effective public policies. It was developed an analysis of the required components for the existence of governability and its relationship with the role of observatories in cities to provide reliable, timely and representative information that allows the formulation of strategies and policies. Governability is enriched with the legitimacy granted by the public from the results obtained by the governments in the formulation, implementation, evaluation of public policies and the evidence based decisions in public health. PMID- 27656940 TI - [Maternal death from severe malaria due to Plasmodium vivax]. AB - Here we describe the case of a 19-year-old woman, in her 29th week of gestation, who was from Llumpe (Ancash, Peru) and had a history of traveling to Chanchamayo (Junin, Peru) and Rinconada (Ancash, Peru). The patient presented at Chacas Hospital (Chacas, Ancash, Peru) with general malaise, dehydration, respiratory distress, jaundice, the sensation of thermal rise, and abdominal pain. Analysis of blood smears revealed 60% hemoparasites. She was transferred to Ramos Guardia Hospital (Huaraz, Peru) where she presented increasing respiratory distress, choluria, hematuria, and decreased urine output, moreover she was positive for Plasmodium. From there she was transferred to Cayetano Heredia Hospital (Lima, Peru), where she was admitted to the intensive care unit (ICU) with multiple organ failure, stillbirth, and leading to death. She underwent mechanical ventilation, was administered clindamycin, and was prescribed quinine, which she did not received due a lack by availability. The evolution of the illness was torpid, and she ultimately developed multiple organ failure and died. Plasmodium vivax infection was confirmed. Accordingly, we emphasize the importance of improving our diagnostic capabilities and management techniques to enable clinicians to provide adequate and timely treatment. PMID- 27656941 TI - [Oral health of the elderly: access, challenges and opportunities for peruvian public health]. PMID- 27656942 TI - [Extended-spectrum beta-lactamase- producing enterobacteriaceae in fecal samples of humans and pets. Chiclayo, Peru]. PMID- 27656943 TI - [Are the MINSA clinical practice guidelines for hypertension and type 2 diabetes mellitus reliable?]. PMID- 27656944 TI - [Law of universal coverage of high-cost diseases]. PMID- 27656945 TI - [Detection of Oropouche viral circulation in Madre de Dios region, Peru (december 2015 to january 2016)]. PMID- 27656946 TI - [Exposure to arsenic as associated factor of the high mortality attributed to renal failure in Puno]. PMID- 27656947 TI - [Perception of violence during medical internship in a peruvian university]. PMID- 27656948 TI - [Not Available]. PMID- 27656949 TI - The Pil3 pilus of Streptococcus gallolyticus binds to intestinal mucins and to fibrinogen. AB - Streptococcus gallolyticus is a commensal bacterium responsible for infectious endocarditis in the elderly, which has frequently been associated with colonic carcinoma. Whether this species is a cause or a consequence of colorectal cancer remains unknown. We recently demonstrated that S. gallolyticus Pil3 pilus is required for adhesion to colonic mucus and for colonization of mouse distal colon. We show here that Pil3 pilus binds equally well to human colonic mucins derived from HT29-MTX cells and to human stomach mucins from healthy donors. In addition, we have found that Pil3 also binds to human fibrinogen, which expands the repertoire of Pil3 host ligands. PMID- 27656950 TI - Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis. AB - Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-alpha 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 MUg/m2 of PEG IFN-alpha 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects. PMID- 27656951 TI - Psychometric properties of the French Canadian version of the Geriatric Anxiety Inventory. AB - BACKGROUND: The Geriatric Anxiety Inventory (GAI) and a short form of this instrument (GAI-SF) were developed to assess the severity of anxiety symptoms in older adults in order to compensate for the lack of validated screening tools adapted to the elderly population. This study examined the psychometric properties of the French Canadian version of the GAI, in its complete (GAI-FC) and short form (GAI-FC-SF). METHOD: A total of 331 community-dwelling seniors between 65 and 92 years old participated in this study. RESULTS: Both the GAI-FC and the GAI-FC-SF have sound psychometric properties with, respectively, a high internal consistency (alpha = .94 and .83), an adequate convergent validity (r = .50 to .86 with instruments known to evaluate constructs similar to the GAI or related to anxiety), a good test-retest reliability (r = .89 and .85), in addition to a single-factor structure. CONCLUSIONS: The results support the use of both the GAI-FC and the GAI-FC-SF. The GAI-FC-SF seems to be an interesting alternative to the GAI-FC as a screening tool when time available for assessment is limited. PMID- 27656952 TI - Effects of AMPK activation on lipolysis in primary rat adipocytes: studies at different glucose concentrations. AB - Adipose tissue plays a key role in energy homeostasis. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important intracellular energy sensor. Effects of activation of AMPK by aminomidazole-4-carboxamide ribonucleotide (AICAR) on lipolysis in the rat adipocytes were determined in the presence of 3 or 12 mM glucose. Response to epinephrine or dibutyryl-cAMP was higher in the presence of 12 mM glucose. AICAR decreased lipolysis, also when glucose was replaced by alanine or succinate and without decrease in cAMP levels. AICAR attenuated epinephrine-induced decrease in adenosine triphosphate (ATP) levels, reduced glucose uptake and lactate release. These results indicate that short-term activation of AMPK by AICAR in the rat adipocytes inhibits lipolysis, due to changes in the final, followed by protein kinase A (PKA), steps of the lipolytic cascade and improves intracellular energy status. Similar effects of AICAR were observed in the presence of 3 and 12 mM glucose, which indicates that the AMPK system is operative at high glucose concentrations. PMID- 27656953 TI - Whole-Body Vibration Exercise Therapy Improves Cardiac Autonomic Function and Blood Pressure in Obese Pre- and Stage 1 Hypertensive Postmenopausal Women. AB - OBJECTIVE: Whole-body vibration (WBV) is an unconventional exercise therapy that appears to provide the same benefits of resistance training in postmenopausal women while being more safe and gentle on the joints. This study evaluated the effect of an 8-week WBV exercise regimen on heart rate variability (HRV) and blood pressure (BP) in obese postmenopausal women. DESIGN: Randomized controlled study with two parallel groups. PARTICIPANTS: Twenty-five (age 50-65 years) obese (body-mass index >30 and <40 kg/m2) postmenopausal women. INTERVENTION: Participants were randomly assigned to a WBV training group or nonexercising control group. Participants in the WBV group completed the supervised training 3 times a week. WBV training consisted of four static and four dynamic leg exercises (normal, high, and wide-stance squats and calf-raises) with vertical vibration (25-40 Hz and low-high amplitude) progressed throughout the 8 weeks. OUTCOME MEASURES: Brachial systolic BP (SBP) and diastolic BP (DBP) and HRV: sympathovagal balance (natural logarithm of low frequency [LnLF]/natural logarithm of high frequency [LnHF]; normalized low frequency [nLF]/normalized high frequency [nHF]), parasympathetic tone (LnHF, nHF, natural logarithm of root mean square of successive differences [LnRMSSD]), sympathetic tone (LnLF, nLF), natural logarithm of total power, and heart rate (HR). RESULTS: There were significant group * time interactions (p < 0.05) for brachial SBP, DBP, LnLF/LnHF, and nLF/nHF that significantly decreased (p < 0.01) after WBV, compared with no changes after control. There was a significant (p < 0.05) increase in nHF and decrease in nLF in the WBV group compared with baseline, yet the changes were not different than those in the control group. No significant changes were observed in LnTP, LnLF, LnHF, LnRMSSD, or HR after 8 weeks in either group. CONCLUSIONS: WBV training for 8 weeks is an adequate unconventional exercise intervention for improving sympathovagal balance and BP in previously sedentary obese postmenopausal women. PMID- 27656954 TI - Pulmonary Artery Pseudoaneurysms: Clinical Features and CT Findings. AB - OBJECTIVE: The purpose of this study was to analyze the clinical and CT features of pulmonary artery pseudoaneurysms (PAPs). MATERIALS AND METHODS: A database search of chest CT examinations performed from January 1, 2000 to December 31, 2014 identified 24 patients with findings consistent with PAPs. A CT finding consistent with a PAP was defined as a focal saccular outpouching of a pulmonary artery. Medical records were reviewed to determine clinical presentations, treatments, and outcomes. CT scans were reviewed by two board-certified fellowship-trained chest radiologists. RESULTS: A total of 35 PAPs were identified in 24 patients. Hemoptysis and shortness of breath were the most common presenting symptoms. The most commonly identified causes of PAPs were infection (33%), neoplasms (13%), and trauma (17%). Of the 35 PAPs, 29 (83%) were located in segmental or subsegmental pulmonary arteries. A solitary PAP was identified in 20 (83%) patients, and multiple PAPs were identified in three patients with endocarditis and one patient with pulmonary metastases. Only three of 35 (9%) PAPs were associated with a ground-glass halo. Endovascular treatment was successfully performed in 12 patients, and only one patient had immediate recurrent hemoptysis after treatment. PAP was clinically suspected by the referring clinicians in only three patients. Sixteen of the 35 (46%) PAPs were not reported on the initial CT studies. CONCLUSION: PAPs showed a strong predilection for the peripheral pulmonary arteries. Multiplicity of PAPs can be seen in the settings of endocarditis and pulmonary metastatic disease. Most PAPs were not associated with a ground-glass halo. PAPs can be lethal but were often not suspected clinically and were underreported by radiologists. PMID- 27656955 TI - Surveying Academic Radiology Department Chairs Regarding New and Effective Strategies for Medical Student Recruitment. AB - OBJECTIVE: The number of 4th-year medical student applications to the field of diagnostic radiology has decreased from 2009 to 2015. The purpose of this study was to learn how radiology departments are recruiting medical students. MATERIALS AND METHODS: An anonymous online survey hyperlink was distributed to the members of the Society of Chairs of Academic Radiology Departments regarding both innovative and proven recruitment strategies. The results were synthesized with a recently published survey of medical students about factors influencing them to go into radiology. RESULTS: Forty of 126 radiology departments completed the survey. Most felt that radiology exposure and curricula require alteration given recent downward trends in medical student applications. A majority (79%) had changed their outreach to medical students in response to these trends. The responding department chairs felt that interactive learning while on rotation was the most important strategy for recruitment. The presence of a diversity program, dedicated medical school educator, or rotating daily assignment for students did not affect the likelihood of filling residency spots in the main match. CONCLUSION: Many radiology departments are changing their outreach to medical students to improve recruitment. Effective strategies to focus on include early active outreach by involving students in the radiology department, thereby framing radiologists as clinicians. PMID- 27656956 TI - Possible Differences in the Effects of Trypanosoma cruzi on Blood Cells and Serum Protein of Two Wildlife Reservoirs. AB - A key step in the dynamics of vector-borne diseases is the role of seasonality. Trypanosoma cruzi is a protozoan that causes Chagas disease. Some wild mammals are considered natural hosts, yet not all mammals show the same response to infection. We explored the effect of T. cruzi on blood parameters in two mammal carnivores, coati (Nasua narica) and raccoon (Procyon lotor), that were naturally infected in summer and winter seasons. The study was carried out in the Zoological Park "Parque Museo de la Venta," in Southeastern Mexico. Blood samples were collected in summer and winter from 2010 to 2013. Parasite infection was assessed by PCR from whole blood, and a complete hemogram was determined by traditional manual methods. We found that both species had the same T. cruzi I lineage. For coatis, mean corpuscular volume, mean corpuscular hemoglobin, and monocytes were dependent of season, while eosinophils and plasma proteins were significantly different, but with no season effect. For raccoon, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, and monocytes were dependent of season. These results and a previous study that indicated interspecific differences in parasitemia in both species suggest that raccoon is a better reservoir than coati. Such a different interspecific response implies that animals do not contribute equally to maintain T. cruzi parasites in the ecosystem. Such inequality differs according to season. PMID- 27656957 TI - How can we improve the quality of transplantable lungs? AB - INTRODUCTION: Optimization of lungs for organ donation is becoming increasingly important as donation rates stagnate despite growing waiting lists. Improving procurement and utilization of donated lungs has the ability to reduce mortality and time on the lung transplantation (LTx) waiting list. Additionally, assessment and optimization of donor lungs can reduce both early and late post-LTx morbidity and mortality, as well as reduce overall costs and resource utility. Areas covered: Strategies that we will discuss in detail include intensive care management practices, such as targeted ventilation protocols and therapeutic bronchoscopy, as well as the ever expanding possibilities within the arena of ex vivo lung perfusion (EVLP). Expert commentary: Donor lung quality is currently optimized both in vivo prior to organ procurement, and also via EVLP circuits. Despite good evidence demonstrating the utility of both approaches, data remain elusive as to whether EVLP is beneficial for all donor lungs prior to implantation, or instead as a tool by which we can evaluate and recondition sub optimal donor lungs. PMID- 27656959 TI - Mid staffs inquiry calls RCN to give evidence. AB - The RCN has been called to give evidence about staffing levels and patient safety to MPs next week in an investigation into the failures at Mid Staffordshire NHS Foundation Trust. PMID- 27656960 TI - Pressure mounts on staff levels as trusts chase foundation status. AB - Nursing posts and healthcare services are coming under increasing threat as NHS bodies chase foundation trust status ahead of next year's deadline, according to the RCN. PMID- 27656961 TI - Staff with learning difficulties need greater support. AB - Nurses have demanded that staff who have dyslexia and similar learning difficulties should be given support and guidance from employers to prevent discrimination and help them to deliver high quality care. PMID- 27656958 TI - Mining bifidobacteria from the neonatal gastrointestinal tract for conjugated linolenic acid production. AB - Conjugated linolenic acid (CLNA) is a family of isomers of linolenic acid with a number of health-associated benefits, which has been attracting great interest. Microbial CLNA producers are potentially an alternative source of CLNA for human nutrition. In present study, 16 neonate feces were collected and used for Bifidobacteria isolation, from which 25 bifidobacteria isolates were obtained. The bifidobacteria isolates were identified using 16s rDNA sequencing as Bifidobacterium adolescentis, B. breve, B. longum and B. pseudocatenulatum. These isolates were further investigated for their ability to produce CLNA using linolenic acid as substrate via GC-MS. The results showed most of the isolates could convert free linolenic acid into c9,t11,c15-CLNA and t9,t11,c15-CLNA at different levels. B. pseudocatenulatum was the most effective CLNA producer, which converted 86.91% of linolenic acid to c9,t11,c15-CLNA and 3.59% of to t9,t11,c15-CLNA isomer and the isolate exhibited to accumulate CLNA during 72 h culturing in which most CLNA isomers were in the supernatant fluid. The results indicated that utilization of this isolate for CLNA production will eliminate the purification process. PMID- 27656964 TI - Appeal for information on D-Day casualty. AB - A second world war nurse is appealing for help to find a seriously injured German soldier she treated, ahead of the 65th anniversary of D-Day next month. PMID- 27656963 TI - Gordon Brown orders honours committee to prioritise nurses. AB - The committees that oversee the honours system have been ordered to give a higher priority to nurses who have been nominated, Nursing Standard has learned. PMID- 27656965 TI - Alcohol services benefit from nurse intervention. AB - The RCN has released clear evidence of a demand for specialist alcohol nursing services and interventions across the UK. PMID- 27656966 TI - Student loans could be part of new financial support package. AB - The non-means tested bursary for nursing students looks set to be scrapped as part of an overhaul of the way students are supported during their courses. PMID- 27656967 TI - Poor work atmosphere can lead to depression and medication use. AB - Depression, anxiety and alcohol use disorders are common mental health problems in the working population. But the 'team climate' - conditions and atmosphere - at work related to these disorders has not previously been studied using standardised interviews. PMID- 27656969 TI - Readers panel. AB - Our experts consider a hot topic of the day. PMID- 27656968 TI - Diagnoses of eczema and treatment for it greatly increased. AB - The incidence and lifetime prevalence of eczema in England continues to increase. Similar increases have been observed in the estimated number of prescriptions issued for eczema. PMID- 27656970 TI - I was hounded out for reporting poor standards. AB - The controversy about Margaret Haywood, who was struck off the Nursing and Midwifery Council register for secretly filming patients to expose poor patient care, shows nothing has changed. PMID- 27656971 TI - Starting out - using relatives as translators creates a barrier to good care. AB - On a recent surgical placement I was asked to observe a staff nurse while she discharged a patient who had undergone heart surgery. The patient was a 48-year old man from a minority ethnic group, who could only speak a small amount of English. PMID- 27656972 TI - The best of the week's health-related TV and radio. AB - Our roundup of what's on. PMID- 27656973 TI - Winningham and preusser's critical thinking cases in nursing Barbara A Preusser Winningham and preusser's critical thinking cases in nursing Fourth Elsevier 720pp L24.99 978 0 323 05359 4 0323053599 [Formula: see text]. AB - At 720pages, this is a weighty book, offering 148 case studies in a range of clinical specialties. And at L24.99, it may appear excellent value for money, especially for impoverished students. PMID- 27656974 TI - A welcome return to old values, but it is what is under the bonnet that counts. AB - I am pleased that nurses at Broomfield Hospital in Chelmsford, Essex are to return to wearing hats (news May 13). Welcoming the white bonnets that are being piloted, the hospital's deputy director of nursing, Catherine Morgan, says: 'We value the professionalism that a smart uniform portrays.' PMID- 27656975 TI - Professional education must remain rigorous and thorough. AB - I was dismayed by David Cameron's speech at the RCN congress in Harrogate (news May 13), even more so when he received a standing ovation. PMID- 27656976 TI - Supermarket training is the last thing nurses need. AB - Judging by Petra Kendall-Raynor's news story, 'Supermarkets used as a model for community nursing productivity' (May 13), it appears that a considerable amount of time, money and energy will be spent 'educating' healthcare professionals on a basic stock control exercise. PMID- 27656977 TI - Like the commons' speaker, the nmc missed the real issue. AB - Last week the speaker of the House of Commons, Michael Martin, expressed concern that details of MPs' expenses had been leaked to the media. The public is much more disturbed by the expenses scandal itself and Mr Martin has been forced out. PMID- 27656978 TI - While unison is at it, why not outlaw the tories as well? AB - I read with interest your piece about Unison's campaign to outlaw nurse's rights to belong to the BNP (news April 29) I suggest they go one step further and implement a ban on Conservative party members. PMID- 27656980 TI - Notice board. AB - Courses, events, grants, and awards to progress your career. PMID- 27656979 TI - Repayment scheme could stop some bursary system abuses. AB - As a mature student, I would not have been able to afford to join a pre registration nursing course without receiving a bursary. PMID- 27656981 TI - Keeping it local. AB - As primary care trusts (PCTs) divide up their commissioning and provider functions, community health services are embroiled in another major reorganisation. Despite apprehension, some community nurses are anticipating exciting opportunities. PMID- 27656983 TI - LIG report causing confusion. AB - The London Implementation Group's widely-leaked report on specialty services in the capital is due to be published this week, causing further confusion and uncertainty for nurses who believed their hospitals were safe from the threat of closure under Tomlinson. PMID- 27656982 TI - Rhetoric versus reality. AB - There are few winners in the London rationalisation exercise, other than the hordes of management consultants invading almost every hospital in the Capital. With the result of the six specialty reviews due to be announced this week, nurses at the Royal Marsden, Harefield and Bart's will certainly not count themselves on the winning side. PMID- 27656984 TI - Review of complaints procedures. AB - The Health Secretary has announced an independent review of NHS complaints procedures, in a move welcomed by the RCN and the UKCC. PMID- 27656985 TI - Policies and prizes as ICN Congress kicks off in Madrid. AB - Nurses from more than 80 countries gathered in Madrid this week for the 20th Quadrennial Congress of the International Council of Nurses. PMID- 27656986 TI - DNs in sight of success in grade cut campaign. AB - District nurses in Liverpool looked close to victory last week in their seven month campaign against plans to halve the number of G grade sisters. PMID- 27656987 TI - Trades union outrage over 'sweeteners'. AB - Nursing unions have condemned an 'outrageous' amendment to the government's trade union legislation that will allow employers to offer 'sweeteners' to staff who give up union membership. PMID- 27656988 TI - ? AB - Bop Nurse: Chief Nursing Officer Yvonne Moores joined health visitors and children in a stretch workout at the Piazza, Covent Garden, to launch Community Healthcare Week, organised by the Health Visitors Association and the Scottish HVA. PMID- 27656989 TI - Plan threatens CPN links with patients. AB - MPs have been warned that compulsory medication of psychiatric patients in the community will be disastrous for community psychiatric nursing. PMID- 27656990 TI - Strike call rejected over pay limits. AB - COHSE members have rejected a call for strike action over the government's 1.5 percent pay limits. PMID- 27656991 TI - Whistleblowers should go straight to their MPs. AB - Nurses should sidestep the government's new 'gagger's charter' by going straight to their MPs with concerns about poor conditions, delegates heard. In an emergency statement to the COHSE conference, the new whistleblowers' guidelines, launched two weeks ago, were dubbed by the statement as a 'cynical PR exercise'. PMID- 27656992 TI - End speculation on RNMH future role. AB - Tlie final conference of COHSE has called for the 'never ending speculation' on the future of mental handicap nursing to be brought to a halt. PMID- 27656994 TI - Confusion over conflicting advice on vitamin K. AB - The RCN has backed the use of oral vitamin K for newborn babies after research showed a possible link between intramuscular preparations of the drug and childhood cancer. PMID- 27656996 TI - ? AB - Mother Teresa of Calcutta addressed the Nursing Faculty at the Royal College of Surgeons in Ireland recently after receiving an Honorary Fellowship from the college. Pictured with her (above) is Jean Bartley. Dean of the Faculty. PMID- 27656997 TI - Ireland. AB - Condom vending machines are slowly being introduced across the Republic of Ireland after new legislation was introduced to allow' them to be installed in pubs, hotels and shops. PMID- 27656998 TI - New Zealand. AB - The New Zealand government has abandoned plans to charge patients up to L20 for overnight stays in hospital. The decision comes at a sensitive time for the government, in the run up to the November general election. PMID- 27656999 TI - United States. AB - Nurses are being made redundant and replaced by unqualified staff as health care reforms leave hospitals facing an uncertain financial future, the American Nurses' Association claimed recently. PMID- 27657002 TI - DNR confusion blamed on poor communication. AB - Poor documentation and inadequate communication between doctors and nurses could explain why nurses are frequently not aware of 'Do Not Resuscitate' (DNR) orders in patient records, a study has found. PMID- 27657000 TI - Terminally ill patients should be allowed to the with dignity. PMID- 27657003 TI - Resources used on those most likely to benefit. AB - Computer-based outcome predictions can alter patient management in neurosurgical units and help staff to concentrate resources on those patients most likely to benefit. PMID- 27657004 TI - Twins more likely to be born with cerebral palsy. AB - Cerebral palsy is more likely among twins and children of low birthweight, according to a new survey by Action Research. PMID- 27657005 TI - Agents for change. AB - Agency nursing is not always perceived as part of the mainstream of the profession. But even if nurses have not worked 'on the agency' themselves, they will certainly work alongside agency nurses at some point. PMID- 27657006 TI - A glittering prize. AB - Dame Sheila Quinn, former President of the RCN, has become the first UK recipient of the Christiane Reimann Prize, often dubbed the 'Nobel Prize for Nursing'. PMID- 27657007 TI - The need to unite. AB - Why is there still no national neonatal screening programme? Why has the government failed to issue specific guidelines concerning the management of sickle cell? Why do sicklers still have to pay prescription charges? Why are counsellors living on shoestring funding, unable to plan for the medium and long term? PMID- 27657008 TI - ? AB - * The author of Victim of false accusations (Viewpoint, June 9) set out the distress caused to her by ill-founded or false accusations of professional misconduct. PMID- 27657009 TI - Gagged by false misconduct claims. AB - Joe Winters (Speak up, Viewpoint, June 9) answers his own question when he asks why nurses are so reluctant to speak up for themselves. Fear of retribution, from employers and through misuse of the UKCC Code of Conduct complaints procedure, is the problem. PMID- 27657010 TI - Time to get away from generalisations. AB - The research quoted in your news item (AIDS: P2000 tailing students, June 2), should be challenged on the grounds of over-generalisation and possible inaccuracy. PMID- 27657011 TI - Short shrift for abbreviations. AB - Could you please spell out the abbreviations in Nursing Standard's articles? PMID- 27657013 TI - Information exchange. AB - * My sister, who is a care nurse at a local nursing home, has told me of the apparent lack of tailored computer software for this particular type of nursing. PMID- 27657012 TI - ? AB - * Phillip Woodrow recently saw fit to compare the Project 2000 course to learning to drive by sitting in the back seat of a car and watching others do the work (Letters, May 26). PMID- 27657014 TI - Peter Kavanagh. AB - It is with deep sadness that I report news of the death of Peter Kavanagh, registrar at the Norfolk College of Nursing and Midwifery, Norwich. PMID- 27657016 TI - Bereavement and Adaptation M P Cleiren Bereavement and Adaptation Hemisphere 296pp L20 1-56032-279-9. AB - There is a growing awareness among those involved in health-related research that Europeans must overcome language barriers in order to share knowledge and ideas. PMID- 27657017 TI - Counselling P Burnard Counselling Buttcrworth/Heinemann 212pp L11.95 0-7506-0643 6. AB - Counselling: A Guide to Practice in Nursing, Philip Burnard says it is 'for any nurse who works with patients', with the view that patients, like ourselves, have a variety of problems and nurses often feel they cannot talk to them. PMID- 27657015 TI - With thanks for all your support. AB - May I thank the many friends and colleagues who have written to me during recent weeks. I am gradually replying to everybody individually. PMID- 27657018 TI - The Art of Counselling R May The Art of Counselling Souvenir 192pp L7.99 0-285 65099-8. AB - Rollo May's The Art of Counselling is an established textbook in the US which has recently been distributed in a British edition. The text is rooted firmly in May's considerable experiences as a counsellor and teacher, and is organised in three parts. PMID- 27657019 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodivorth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Pax: 081-423 3867. PMID- 27657020 TI - Molecular Modeling Studies of 11beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations. AB - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11beta-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11beta-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11beta-HSD1 inhibitors. PMID- 27657021 TI - Two New Clerodane Diterpenes from Tinospora sagittata. AB - Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5). The structures of these compounds were determined on the basis of spectroscopic data interpretation, with that of the absolute configuration of compound 1 was assigned by experimental and calculated ECD spectra. The cytotoxicity and alpha glucosidase inhibitory activities of isolated compounds were evaluated in vitro. PMID- 27657022 TI - Comparison of the Antioxidant Effects of Quercitrin and Isoquercitrin: Understanding the Role of the 6"-OH Group. AB - The role of the 6"-OH (omega-OH) group in the antioxidant activity of flavonoid glycosides has been largely overlooked. Herein, we selected quercitrin (quercetin 3-O-rhamnoside) and isoquercitrin (quercetin-3-O-glucoside) as model compounds to investigate the role of the 6"-OH group in several antioxidant pathways, including Fe2+-binding, hydrogen-donating (H-donating), and electron-transfer (ET). The results revealed that quercitrin and isoquercitrin both exhibited dose dependent antioxidant activities. However, isoquercitrin showed higher levels of activity than quercitrin in the Fe2+-binding, ET-based ferric ion reducing antioxidant power, and multi-pathways-based superoxide anion-scavenging assays. In contrast, quercitrin exhibited greater activity than isoquercitrin in an H donating-based 1,1-diphenyl-2-picrylhydrazyl radical-scavenging assay. Finally, in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl assay based on an oxidatively damaged mesenchymal stem cell (MSC) model, isoquercitrin performed more effectively as a cytoprotector than quercitrin. Based on these results, we concluded that (1) quercitrin and isoquercitrin can both indirectly (i.e., Fe2+ chelating or Fe2+-binding) and directly participate in the scavenging of reactive oxygen species (ROS) to protect MSCs against ROS-induced oxidative damage; (2) the 6"-OH group in isoquercitrin enhanced its ET and Fe2+-chelating abilities and lowered its H-donating abilities via steric hindrance or H-bonding compared with quercitrin; and (3) isoquercitrin exhibited higher ROS scavenging activity than quercitrin, allowing it to improve protect MSCs against ROS-induced oxidative damage. PMID- 27657023 TI - On the Effect of Microwave Energy on Lipase-Catalyzed Polycondensation Reactions. AB - Microwave energy (MWe) is, nowadays, widely used as a clean synthesis tool to improve several chemical reactions, such as drug molecule synthesis, carbohydrate conversion and biomass pyrolysis. On the other hand, its exploitation in enzymatic reactions has only been fleetingly investigated and, hence, further study of MWe is required to reach a precise understanding of its potential in this field. Starting from the authors' experience in clean synthesis and biocatalyzed reactions, this study sheds light on the possibility of using MWe for enhancing enzyme-catalyzed polycondensation reactions and pre-polymer formation. Several systems and set ups were investigated involving bulk and organic media (solution phase) reactions, different enzymatic preparations and various starting bio-based monomers. Results show that MWe enables the biocatalyzed synthesis of polyesters and pre-polymers in a similar way to that reported using conventional heating with an oil bath, but in a few cases, notably bulk phase polycondensations under intense microwave irradiation, MWe leads to a rapid enzyme deactivation. PMID- 27657024 TI - Asiatic Acid Attenuates Myocardial Ischemia/Reperfusion Injury via Akt/GSK 3beta/HIF-1alpha Signaling in Rat H9c2 Cardiomyocytes. AB - Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this study, we determined the effect of asiatic acid on myocardial ischemia/reperfusion injury and investigated the underlying mechanisms, using an in vitro rat H9c2 cardiomyocytes model of oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Results showed that pre-treatment with asiatic acid significantly augmented cell viability and prevented lactate dehydrogenase (LDH) release in a concentration-dependent manner after OGD/R exposure. Asiatic acid at 10 MUM effectively inhibited apoptotic cell death, suppressed the activities of caspase-3 and caspase-9, and reversed Bax/Bcl-2 ratio in hypoxic H9c2 cells. In addition, asiatic acid improved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS) accumulation, enhanced mitochondrial membrane potential and decreased intracellular calcium concentration. Using Western blot assay, we found that asiatic acid promoted the phosphorylation of Akt and subsequent inactivation of glycogen synthase kinase 3beta (GSK-3beta), and induced the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) after OGD/R. The cardioprotective effects of asiatic acid were attenuated by the Akt or HIF-1alpha inhibitor. Taken together, these data suggested that asiatic acid exerted protective effects against OGD/R-induced apoptosis in cardiomyocytes, at least partly via the Akt/GSK-3beta/HIF-1alpha pathway. PMID- 27657025 TI - The Use of Mass Spectrometric Techniques to Differentiate Isobaric and Isomeric Flavonoid Conjugates from Axyris amaranthoides. AB - Flavonoids are a group of compounds that are commonly found in various plants, where they play important roles in many processes, including free radical scavenging and UV protection. These compounds can also act as chemical messengers, physiological regulators or protectants against pathogens in the defense reactions of plants. Flavonoid activity is regulated by the addition of various substituents, usually mono- or oligosaccharides of common sugars, such as glucose, rhamnose or galactose. In some plants, glucuronic acid is attached, and this sugar is often acylated by phenylpropanoic acids. Identification of these compounds and their derivatives is of great importance to understanding their role in plant metabolism and defense mechanisms; this research is important because flavonoids are frequently a significant constituent of the human diet. In this study, we identify the flavonoid conjugates present in Axyris amaranthoides L. extracts and demonstrate the usefulness of high-resolution mass spectrometry (HRMS) analyzers for the differentiation of isobaric compounds and the utility of fragmentation spectra for the differentiation of isomeric structures. According to our knowledge, some of the structures, especially dehydrodiferulated conjugates of tricin, whose structures are proposed here have been found for the first time in plant material. PMID- 27657026 TI - Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy. AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect of neurotoxic anticancer medicines. It leads to autonomic and somatic system dysfunction and decreases the patient's quality of life. This side effect eventually causes chemotherapy non-compliance. Patients are prompted to seek alternative treatment options since there is no conventional remedy for CIPN. A range of medicinal herbs have multifarious effects, and they have shown some evidence of efficacy in various neurological and immunological diseases. While CIPN has multiple mechanisms of neurotoxicity, these phytomedicines might offer neuronal protection or regeneration with the multiple targets in CIPN. Thus far, researchers have investigated the therapeutic benefits of several herbs, herbal formulas, and phytochemicals in preventing the onset and progress of CIPN in animals and humans. Here, we summarize current knowledge regarding the role of phytochemicals, herb extracts, and herbal formulas in alleviating CIPN. PMID- 27657027 TI - Digital Gene Expression Profiling to Explore Differentially Expressed Genes Associated with Terpenoid Biosynthesis during Fruit Development in Litsea cubeba. AB - Mountain pepper (Litseacubeba (Lour.) Pers.) (Lauraceae) is an important industrial crop as an ingredient in cosmetics, pesticides, food additives and potential biofuels. These properties are attributed to monoterpenes and sesquiterpenes. However, there is still no integrated model describing differentially expressed genes (DEGs) involved in terpenoid biosynthesis during the fruit development of L. cubeba. Here, we performed digital gene expression (DGE) using the Illumina NGS platform to evaluated changes in gene expression during fruit development in L. cubeba. DGE generated expression data for approximately 19354 genes. Fruit at 60 days after flowering (DAF) served as the control, and a total of 415, 1255, 449 and 811 up-regulated genes and 505, 1351, 1823 and 1850 down-regulated genes were identified at 75, 90, 105 and 135 DAF, respectively. Pathway analysis revealed 26 genes involved in terpenoid biosynthesis pathways. Three DEGs had continued increasing or declining trends during the fruit development. The quantitative real-time PCR (qRT-PCR) results of five differentially expressed genes were consistent with those obtained from Illumina sequencing. These results provide a comprehensive molecular biology background for research on fruit development, and information that should aid in metabolic engineering to increase the yields of L. cubeba essential oil. PMID- 27657028 TI - Delivery of RNAi Therapeutics to the Airways-From Bench to Bedside. AB - RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside. PMID- 27657030 TI - The Suppressive Effects of Cinnamomi Cortex and Its Phytocompound Coumarin on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats. AB - Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced cold allodynia in rats and the mechanisms involved. A single oxaliplatin injection (6 mg/kg, i.p.) induced significant cold allodynia signs based on tail immersion tests using cold water (4 degrees C). Daily oral administration of water extract of C. Cortex (WECC) (100, 200, and 400 mg/kg) for five consecutive days following an oxaliplatin injection dose dependently alleviated cold allodynia with only a slight difference in efficacies between the middle dose at 200 mg/kg and the highest dose at 400 mg/kg. WECC at 200 mg/kg significantly suppressed the activation of astrocytes and microglia and decreased the expression levels of IL-1beta and TNF in the spinal cord after injection with oxaliplatin. Furthermore, oral administration of coumarin (10 mg/kg), a major phytocompound of C. Cortex, markedly reduced cold allodynia. These results indicate that C. Cortex has a potent anti-allodynic effect in oxaliplatin-injected rats through inhibiting spinal glial cells and pro inflammatory cytokines. We also suggest that coumarin might play a role in the anti-allodynic effect of C. Cortex. PMID- 27657029 TI - Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line. AB - The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb-drug interactions with 5-Fluorouracil (5 FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism. PMID- 27657031 TI - Silver Nanocomposite Biosynthesis: Antibacterial Activity against Multidrug Resistant Strains of Pseudomonas aeruginosa and Acinetobacter baumannii. AB - Bacterial resistance is an emerging public health issue that is disseminated worldwide. Silver nanocomposite can be an alternative strategy to avoid Gram positive and Gram-negative bacteria growth, including multidrug-resistant strains. In the present study a silver nanocomposite was synthesized, using a new green chemistry process, by the addition of silver nitrate (1.10-3 mol.L-1) into a fermentative medium of Xanthomonas spp. to produce a xanthan gum polymer. Transmission electron microscopy (TEM) was used to evaluate the shape and size of the silver nanoparticles obtained. The silver ions in the nanocomposite were quantified by flame atomic absorption spectrometry (FAAS). The antibacterial activity of the nanomaterial against Escherichia coli (ATCC 22652), Enterococcus faecalis (ATCC 29282), Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923) was carried out using 500 mg of silver nanocomposite. Pseudomonas aeruginosa and Acinetobacter baumannii multidrug-resistant strains, isolated from hospitalized patients were also included in the study. The biosynthesized silver nanocomposite showed spherical nanoparticles with sizes smaller than 10 nm; 1 g of nanocomposite contained 49.24 ug of silver. Multidrug resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, and the other Gram-positive and Gram-negative bacteria tested, were sensitive to the silver nanocomposite (10-12.9 mm of inhibition zone). The biosynthesized silver nanocomposite seems to be a promising antibacterial agent for different applications, namely biomedical devices or topical wound coatings. PMID- 27657033 TI - Effects of Dihydrophaseic Acid 3'-O-beta-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation. AB - Our previous study showed that ethanol extract of Lyciiradicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation enhancing effect of LRC extract. A known sesquiterpene glucoside, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3'-O-beta-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis. PMID- 27657032 TI - Virtual Screening for Potential Allosteric Inhibitors of Cyclin-Dependent Kinase 2 from Traditional Chinese Medicine. AB - Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. The binding site of the ATP-competition inhibitors and the allosteric inhibitors are partially overlapped in space position, so the same compound might interact with the two binding sites. Thus a novel screening strategy was essential for the discovery of pure CDK2 allosteric inhibitors. In this study, pharmacophore and molecular docking were used to screen potential CDK2 allosteric inhibitors and ATP competition inhibitors from Traditional Chinese Medicine (TCM). In the docking result of the allosteric site, the compounds which can act with the CDK2 ATP site were discarded, and the remaining compounds were regarded as the potential pure allosteric inhibitors. Among the results, prostaglandin E1 and nordihydroguaiaretic acid (NDGA) were available and their growth inhibitory effect on human HepG2 cell lines was determined by MTT assay. The two compounds could substantially inhibit the growth of HepG2 cell lines with an estimated IC50 of 41.223 MUmol/L and 45.646 MUmol/L. This study provides virtual screening strategy of allosteric compounds and a reliable method to discover potential pure CDK2 allosteric inhibitors from TCM. Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors. PMID- 27657034 TI - Optimized Conditions for Passerini-Smiles Reactions and Applications to Benzoxazinone Syntheses. AB - Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. PMID- 27657035 TI - Promiscuous Effects of Some Phenolic Natural Products on Inflammation at Least in Part Arise from Their Ability to Modulate the Expression of Global Regulators, Namely microRNAs. AB - Recent years have seen the exploration of a puzzling number of compounds found in human diet that could be of interest for prevention or treatment of various pathologies. Although many of these natural products (NPs) have long been used as remedies, their molecular effects still remain elusive. With the advent of biotechnology revolution, NP studies turned from chemistry and biochemistry toward global analysis of gene expression. Hope is to use genetics to identify groups of patient for whom certain NPs or their derivatives may offer new preventive or therapeutic treatments. Recently, microRNAs have gained the statute of global regulators controlling cell homeostasis by regulating gene expression through genetic and epigenetic regulatory loops. Realization that certain plant polyphenols can modify microRNA expression and thus impact gene expression globally, initiated new, mainly in vitro studies, in particular to determine phytochemicals effects on inflammatory response, whose exacerbation has been linked to several disorders including cancer, auto-immune, metabolic, cardiovascular and neuro-inflammatory diseases. However, very few mechanistic insights have been provided, given the complexity of genetic regulatory networks implicated. In this review, we will concentrate on data showing the potential interest of some plant polyphenols in manipulating the expression of pro- and anti-inflammatory microRNAs in pathological conditions. PMID- 27657036 TI - Antiangiogenic Effects of VH02, a Novel Urea Derivative: In Vitro and in Vivo Studies. AB - Vascular endothelial growth factor receptor 2 (VEGFR2) is a vital target for therapeutic intervention in cancer. We have recently described a computer-based drug design for a small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6 yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-chloromethylphenyl)urea). This study aimed to further explore the anti-angiogenic activity of VH02 both in vitro and in vivo. The in vitro assays include cell viability, capillary-like tube formation, MMP activity, and western blot analyses of signaling through VEGFR2 while the in vivo anti-angiogenic response were performed to evaluate the effect on vascularization in Matrigel plug applied in C57BL/6L mice. VH02 reduced angiogenesis behavior of EA.hy926 including cell viability, migration, adhesion, capillary-like tube formation, and MMP-2 activity induced by VEGF. Furthermore, VH02 regulated angiogenesis by directly inhibiting VEGFR2 on Tyr1175 signaling pathway leading to the inhibition of Akt-mediated cell survival and migration. Disruption of phosphorylation at VEGFR2-Tyr1175 by VH02 abolished FAK-Tyr397 signaling but not phosphorylation of p38 MAPK. This suggests that blockade of FAK by VH02 apparently associated with reduction of endothelial cell motility. Actin cytoskeleton rearrangement was diminished by VH02 in human endothelial cells. The anti-angiogenic effect of VH02 was confirmed in the in vivo model, revealing the reduction of vascular density in Matrigel plug after VH02 treatment. Additionally, the pericyte-like cells surrounding blood vessels in the plugs were significantly reduced as well as vascular density and p-Akt intensity. Our findings indicate that VH02 successfully inhibits VEGF-induced angiogenesis both in vitro and in vivo models. The compound could be further developed as an antiangiogenesis agent for cancer therapy. PMID- 27657037 TI - The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes. AB - The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe) in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS)-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ)-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABAA receptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy. PMID- 27657038 TI - New Oral Formulation and in Vitro Evaluation of Docetaxel-Loaded Nanomicelles. AB - Intravenous administration of Taxotere(r) (a commercial form of docetaxel, DTX) leads to many problems such as hypersensitivity, hemolysis, cutaneous allergy, and patient refusal due to its prolonged injection. The oral absorption of DTX is very low due to its hydrophobic nature. The purpose of this study was to prepare and carry out an in vitro evaluation of DTX-loaded nanomicelles for oral administration in order to increase the oral delivery of DTX. Studied formulations were prepared with the two surfactants Tween 20 and Tween 80 and were characterized for their particle size, zeta potential, stability, encapsulation efficiency, stability studies in gastric fluid and intestinal fluid, toxicity studies in C26 colon carcinoma cell line, and cellular uptake. The prepared nanomicelles with particle size of around 14 nm and encapsulation efficiency of 99% were stable in gastric fluid and intestinal fluid for at least 6 h and IC50 decreased significantly after 72 h exposure compared to that of Taxotere(r). Nanomicelles increased the water solubility of DTX more than 1500 times (10 mg/mL in nanomicelles compared to 6 ug/mL in water). Results of this study reveal that the new formulation of DTX could be used for the oral delivery of DTX and merits further investigation. PMID- 27657039 TI - Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects. AB - Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to fruits, but its content in raspberries and strawberries is low. It has a good radical scavenging capacity (RSC) against superoxide but not hydroxyl radicals, and its oxidative potential is pH-dependent (58 mV/pH unit). After intake, Cy3G can be metabolized (phases I, II) by oral epithelial cells, absorbed by the gastric epithelium (1%-10%) and it is gut-transformed (phase II & microbial metabolism), reaching the bloodstream (<1%) and urine (about 0.02%) in low amounts. In humans and Caco-2 cells, Cy3G's major metabolites are protocatechuic acid and phloroglucinaldehyde which are also subjected to entero hepatic recycling, although caffeic acid and peonidin-3-glucoside seem to be strictly produced in the large bowel and renal tissues. Solid evidence supports Cy3G's bioactivity as DNA-RSC, gastro protective, anti-inflammatory, anti thrombotic chemo-preventive and as an epigenetic factor, exerting protection against Helicobacter pylori infection, age-related diseases, type 2 diabetes, cardiovascular disease, metabolic syndrome and oral cancer. Most relevant mechanisms include RSC, epigenetic action, competitive protein-binding and enzyme inhibition. These and other novel aspects on Cy3G's physical-chemistry, foodomics, and health effects are discussed. PMID- 27657040 TI - Correction: G. Bradley Schaefer. Clinical Genetic Aspects of ASD Spectrum Disorders. Int. J. Mol. Sci. 2016, 17, 180. AB - The author wishes to make a change to the published paper [1].[...]. PMID- 27657041 TI - DNA Interaction Studies of Selected Polyamine Conjugates. AB - The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 * 106 M-1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores. PMID- 27657042 TI - Effect of Thyrotropin on Osteopontin, Integrin alphavbeta3, and VCAM-1 in the Endothelium via Activation of Akt. AB - Numerous epidemiological studies have shown that subclinical hypothyroidism (SCH) can impair endothelial function and cause dyslipidemia. Studies have evaluated the effects of thyroid stimulating hormone (TSH) on endothelial cells, but the mechanism underlying the proatherosclerotic effect of increased TSH levels remains unclear. In the present study, SCH rat models were established in thyroidectomized Wistar rats that were given L-T4 daily. The results showed that in vivo, the expression of osteopontin (OPN) vascular cell adhesion molecule (VCAM-1), and levels of integrin alphavbeta3 in the aortic tissue in SCH and Hypothyroidism (CH) groups was higher than in the control group. However, the effect in the SCH group was higher than in the CH group. In vitro, results showed that different concentration and time gradients of TSH stimulation could increase the expression of OPN, VCAM-1, and integrin alphavbeta3, and this was accompanied by extracellular signal regulated kinase 1/2 (Erk1/2) and Akt activation in human umbilical vein endothelial cells (HUVECs). TSH induced elevation of these proatherosclerotic factors was partially suppressed by a specific Akt inhibitor but not by a specific Erk inhibitor. Findings suggested that the endothelial dysfunction caused by SCH was related to increased proatherosclerotic factors induced by TSH via Akt activation. PMID- 27657043 TI - Recent Advances in Antimicrobial Polymers: A Mini-Review. AB - Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting pathogens and have received considerable attention in both academic and industrial research. This mini-review presents the advances made in antimicrobial polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and polymer material types containing bound or leaching antimicrobials are introduced. This article also addresses the applications of these antimicrobial polymers in the medical, food, and textile industries. PMID- 27657045 TI - Salinity-Induced Variation in Biochemical Markers Provides Insight into the Mechanisms of Salt Tolerance in Common (Phaseolus vulgaris) and Runner (P. coccineus) Beans. AB - The evaluation of biochemical markers is important for the understanding of the mechanisms of tolerance to salinity of Phaseolus beans. We have evaluated several growth parameters in young plants of three Phaseolus vulgaris cultivars subjected to four salinity levels (0, 50, 100, and 150 mM NaCl); one cultivar of P. coccineus, a closely related species reported as more salt tolerant than common bean, was included as external reference. Biochemical parameters evaluated in leaves of young plants included the concentrations of ions (Na+, K+, and Cl-), osmolytes (proline, glycine betaine, and total soluble sugars), and individual soluble carbohydrates. Considerable differences were found among cultivars, salinity levels, and in their interaction for most traits. In general, the linear component of the salinity factor for the growth parameters and biochemical markers was the most important. Large differences in the salinity response were found, with P. vulgaris cultivars "The Prince" and "Maxidor" being, respectively, the most susceptible and tolerant ones. Our results support that salt stress tolerance in beans is mostly based on restriction of Na+ (and, to a lesser extent, also of Cl-) transport to shoots, and on the accumulation of myo-inositol for osmotic adjustment. These responses to stress during vegetative growth appear to be more efficient in the tolerant P. vulgaris cultivar "Maxidor". Proline accumulation is a reliable marker of the level of salt stress affecting Phaseolus plants, but does not seem to be directly related to stress tolerance mechanisms. These results provide useful information on the responses to salinity of Phaseolus. PMID- 27657044 TI - Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back. AB - Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice. PMID- 27657047 TI - Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1. AB - The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated osteoclast-mediated bone resorption. It is reported that monocytes/macrophage progenitor cells or either hematopoietic stem cells (HSCs) gave rise to multinucleated osteoclasts. Thus, inhibition of osteoclastic bone resorption generally seems to be a predominant therapy for treating osteoporosis. Recently, more and more natural compounds have been discovered, which have the ability of inhibiting osteoclast differentiation and fusion. Alliin (S-allyl-l-cysteine sulfoxides, SACSO) is the major component of aged garlic extract (AGE), bearing broad-spectrum natural antioxidant properties. However, its effects on bone health have not yet been explored. Hence, we designed the current study to explore its effects and role in receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast fusion and differentiation. It was revealed that alliin had an inhibitory effect in osteoclasteogenesis with a dose-dependent manner via blocking the c-Fos-NFATc1 signaling pathway. In addition, alliin decreased the generation of reactive oxygen species (ROS) and down-regulated the expression of NADPH oxidase 1 (Nox1). The overall results revealed that alliin could be a potential therapeutic agent in the treatment of osteoporosis. PMID- 27657048 TI - Metabolomics Analysis of the Larval Head of the Silkworm, Bombyx mori. AB - The head, which performs many biological functions, is the most complicated structure of an insect. Development, locomotor behavior, food intake, environmental sensing, and signal transduction are all controlled by the insect's head. As a well-studied insect in Lepidoptera, the silkworm head has an additional function of spinning silk fibers. To understand which molecules are involved in these physiological activities, we performed a metabolomics analysis of silkworm heads. By integrating GC-MS and LC-MS/MS, 90 metabolites were identified in the larval heads of silkworms. These were classified into 13 categories, including amino acids, sugars, organic acids, nucleotides, alcohols, and fatty acids. Informatics analysis revealed that these metabolites are involved in cellular processes, environmental information processing, genetic information processing, human diseases, metabolism, organismal systems, and other pathways. The identified metabolites and pathways are involved in biological processes such as signal transduction, carbohydrate metabolism, endocrine activities, and sensory activities; reflecting the functions of various organs in silkworm heads. Thus, our findings provide references which elucidate the potential functions of the silkworm head and will be of great value for the metabolomics research of silkworms and other insects. PMID- 27657046 TI - Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration. AB - Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration. PMID- 27657050 TI - Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples. AB - In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research. PMID- 27657049 TI - Reactivities of Quinone Methides versus o-Quinones in Catecholamine Metabolism and Eumelanin Biosynthesis. AB - Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates and paved way for the establishment of well-known Raper-Mason pathway for the biogenesis of brown to black eumelanins. Tyrosinase catalyzes the oxidation of tyrosine as well as dopa to dopaquinone. Dopaquinone thus formed, undergoes intramolecular cyclization to form leucochrome, which is further oxidized to dopachrome. Dopachrome is either converted into 5,6-dihydroxyindole by decarboxylative aromatization or isomerized into 5,6-dihydroxyindole-2-carboxylic acid. Oxidative polymerization of these two dihydroxyindoles eventually produces eumelanin pigments via melanochrome. While the role of quinones in the biosynthetic pathway is very well acknowledged, that of isomeric quinone methides, however, remained marginalized. This review article summarizes the key role of quinone methides during the oxidative transformation of a vast array of catecholamine derivatives and brings out the importance of these transient reactive species during the melanogenic process. In addition, possible reactions of quinone methides at various stages of melanogenesis are discussed. PMID- 27657052 TI - Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD). AB - Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD). To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD-and to support future biomarker development-we profiled the serum lipidomes of healthy smokers, smokers with mild to moderate COPD (GOLD stages 1 and 2), former smokers, and never-smokers (n = 40 per group) (ClinicalTrials.gov registration: NCT01780298). Serum lipidome profiling was conducted with untargeted and targeted mass spectrometry-based lipidomics. Guided by weighted lipid co-expression network analysis, we identified three main trends comparing smokers, especially those with COPD, with non-smokers: a general increase in glycero(phospho)lipids, including triglycerols; changes in fatty acid desaturation (decrease in omega-3 polyunsaturated fatty acids, and an increase in monounsaturated fatty acids); and an imbalance in eicosanoids (increase in 11,12- and 14,15-DHETs (dihydroxyeicosatrienoic acids), and a decrease in 9- and 13-HODEs (hydroxyoctadecadienoic acids)). The lipidome profiles supported classification of study subjects as smokers or non-smokers, but were not sufficient to distinguish between smokers with and without COPD. Overall, our study yielded further insights into the complex interplay between smoke exposure, lung disease, and systemic alterations in serum lipid profiles. PMID- 27657053 TI - Protein Kinases and Parkinson's Disease. AB - Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson's disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson's disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson's disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules. PMID- 27657054 TI - Candida antarctica Lipase B Immobilized onto Chitin Conjugated with POSS(r) Compounds: Useful Tool for Rapeseed Oil Conversion. AB - A new method is proposed for the production of a novel chitin-polyhedral oligomeric silsesquioxanes (POSS) enzyme support. Analysis by such techniques as X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy confirmed the effective functionalization of the chitin surface. The resulting hybrid carriers were used in the process of immobilization of the lipase type b from Candida antarctica (CALB). Fourier transform infrared spectroscopy (FTIR) confirmed the effective immobilization of the enzyme. The tests of the catalytic activity showed that the resulting support-biocatalyst systems remain hydrolytically active (retention of the hydrolytic activity up to 87% for the chitin + Methacryl POSS(r) cage mixture (MPOSS) + CALB after 24 h of the immobilization), as well as represents good thermal and operational stability, and retain over 80% of its activity in a wide range of temperatures (30-60 degrees C) and pH (6-9). Chitin POSS-lipase systems were used in the transesterification processes of rapeseed oil at various reaction conditions. Produced systems allowed the total conversion of the oil to fatty acid methyl esters (FAME) and glycerol after 24 h of the process at pH 10 and a temperature 40 degrees C, while the Methacryl POSS(r) cage mixture (MPOSS) was used as a chitin-modifying agent. PMID- 27657056 TI - Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis? AB - Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58-77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004-1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075-1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998-1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient collective suffering from pre-diabetes or undiagnosed diabetes with its' known adverse consequences, especially in the long-term. Hyperglycemia in sepsis might be considered as adaptive survival mechanism to hypo-perfusion and consecutive lack of glucose in peripheral cells. AMI patients with hyperglycemic derailment during an ICU-stay should be closely followed-up and extensively screened for diabetes to improve patients' outcome. PMID- 27657051 TI - Molecular Pathogenesis of NASH. AB - Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression. PMID- 27657057 TI - New Phase of Growth for Xenogeneic-Based Bioartificial Organs. AB - In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent shortage of organs available for allotransplantation. The widespread introduction and adoption of bioengineered organs, incorporating cells and tissues derived from either human or animal sources, would help address this shortage. Despite the decades of development, the variety of organs studied and bioengineered, and continuous progress in the field, only two bioengineered systems are currently commercially available: Apligraf(r) and Dermagraft(r) are both approved by the FDA to treat diabetic foot ulcers, and Apligraf(r) is approved to treat venous leg ulcers. Currently, no products based on xenotransplantation have been approved by the FDA. Risk factors include immunological barriers and the potential infectivity of porcine endogenous retrovirus (PERV), which is unique to xenotransplantation. Recent breakthroughs in gene editing may, however, mitigate risks related to PERV. Because of its primary role in interrupting progress in xenotransplantation, we present a risk assessment for PERV infection, and conclude that the formerly high risk has been reduced to a moderate level. Advances in gene editing, and more broadly in the field, may make it more likely than ever before that bioartificial organs will alleviate the suffering of patients with organ failure. PMID- 27657055 TI - Structure-Based Reverse Vaccinology Failed in the Case of HIV Because it Disregarded Accepted Immunological Theory. AB - Two types of reverse vaccinology (RV) should be distinguished: genome-based RV for bacterial vaccines and structure-based RV for viral vaccines. Structure-based RV consists in trying to generate a vaccine by first determining the crystallographic structure of a complex between a viral epitope and a neutralizing monoclonal antibody (nMab) and then reconstructing the epitope by reverse molecular engineering outside the context of the native viral protein. It is based on the unwarranted assumption that the epitope designed to fit the nMab will have acquired the immunogenic capacity to elicit a polyclonal antibody response with the same protective capacity as the nMab. After more than a decade of intensive research using this type of RV, this approach has failed to deliver an effective, preventive HIV-1 vaccine. The structure and dynamics of different types of HIV-1 epitopes and of paratopes are described. The rational design of an anti-HIV-1 vaccine is shown to be a misnomer since investigators who claim that they design a vaccine are actually only improving the antigenic binding capacity of one epitope with respect to only one paratope and not the immunogenic capacity of an epitope to elicit neutralizing antibodies. Because of the degeneracy of the immune system and the polyspecificity of antibodies, each epitope studied by the structure-based RV procedure is only one of the many epitopes that the particular nMab is able to recognize and there is no reason to assume that this nMab must have been elicited by this one epitope of known structure. Recent evidence is presented that the trimeric Env spikes of the virus possess such an enormous plasticity and intrinsic structural flexibility that it is it extremely difficult to determine which Env regions are the best candidate vaccine immunogens most likely to elicit protective antibodies. PMID- 27657058 TI - Cancer Cell Fusion: Mechanisms Slowly Unravel. AB - Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so. PMID- 27657060 TI - McDonald Criteria 2010 and 2005 Compared: Persistence of High Oligoclonal Band Prevalence Despite Almost Doubled Diagnostic Sensitivity. AB - The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral immunoreaction in the form of oligoclonal bands (OCB) is crucial in the diagnostic workup. To date, the impact of the 2010 McDonald criteria on the prevalence of OCB has not been investigated. We retrospectively evaluated data of 325 patients with a clinical relapse suggestive of demyelination that were treated in a German university hospital between 2010 and 2015. One hundred thirty-six patients (42%) were diagnosed with MS and 189 patients with CIS when the criteria of 2010 were applied. The criteria of 2005 allowed only 70 patients (22%) to be designated as MS. In contrast, the prevalence of OCB was marginal affected in MS patients with 96% for the criteria of 2010 and 98.5% for the criteria of 2005. In conclusion, OCB are prevalent in most MS patients and reflect the chronic inflammatory nature of the disease. We recommend CSF examination to exclude alternative diagnoses and reevaluation of the diagnosis MS in patients with negative OCB. PMID- 27657063 TI - A Sparsity-Promoted Decomposition for Compressed Fault Diagnosis of Roller Bearings. AB - The traditional approaches for condition monitoring of roller bearings are almost always achieved under Shannon sampling theorem conditions, leading to a big-data problem. The compressed sensing (CS) theory provides a new solution to the big data problem. However, the vibration signals are insufficiently sparse and it is difficult to achieve sparsity using the conventional techniques, which impedes the application of CS theory. Therefore, it is of great significance to promote the sparsity when applying the CS theory to fault diagnosis of roller bearings. To increase the sparsity of vibration signals, a sparsity-promoted method called the tunable Q-factor wavelet transform based on decomposing the analyzed signals into transient impact components and high oscillation components is utilized in this work. The former become sparser than the raw signals with noise eliminated, whereas the latter include noise. Thus, the decomposed transient impact components replace the original signals for analysis. The CS theory is applied to extract the fault features without complete reconstruction, which means that the reconstruction can be completed when the components with interested frequencies are detected and the fault diagnosis can be achieved during the reconstruction procedure. The application cases prove that the CS theory assisted by the tunable Q-factor wavelet transform can successfully extract the fault features from the compressed samples. PMID- 27657059 TI - Multiplex Gene Expression Profiling of 16 Target Genes in Neoplastic and Non Neoplastic Canine Mammary Tissues Using Branched-DNA Assay. AB - Mammary gland tumors are one of the most common neoplasms in female dogs, and certain breeds are prone to develop the disease. The use of biomarkers in canines is still restricted to research purposes. Therefore, the necessity to analyze gene profiles in different mammary entities in large sample sets is evident in order to evaluate the strength of potential markers serving as future prognostic factors. The aim of the present study was to analyze the gene expression of 16 target genes (BRCA1, BRCA2, FOXO3, GATA4, HER2, HMGA1, HMGA2, HMGB1, MAPK1, MAPK3, MCL1, MYC, PFDN5, PIK3CA, PTEN, and TP53) known to be involved in human and canine mammary neoplasm development. Expression was analyzed in 111 fresh frozen (FF) and in 170 formalin-fixed, paraffin-embedded (FFPE) specimens of neoplastic and non-neoplastic canine mammary tissues using a multiplexed branched DNA (b-DNA) assay. TP53, FOXO3, PTEN, and PFDN5 expression revealed consistent results with significant low expression in malignant tumors. The possibility of utilizing them as predictive factors as well as for assisting in the choice of an adequate gene therapy may help in the development of new and improved approaches in canine mammary tumors. PMID- 27657062 TI - Anthocyanin Attenuates Doxorubicin-Induced Cardiomyotoxicity via Estrogen Receptor-alpha/beta and Stabilizes HSF1 to Inhibit the IGF-IIR Apoptotic Pathway. AB - Doxorubicin (Dox) is extensively used for chemotherapy in different types of cancer, but its use is limited to because of its cardiotoxicity. Our previous studies found that doxorubicin-induced insulin-like growth factor II receptor (IGF-IIR) accumulation causes cardiomyocytes apoptosis via down-regulation of HSF1 pathway. In these studies, we demonstrated a new mechanism through which anthocyanin protects cardiomyoblast cells against doxorubicin-induced injury. We found that anthocyanin decreased IGF-IIR expression via estrogen receptors and stabilized heat shock factor 1 (HSF1) to inhibit caspase 3 activation and apoptosis of cardiomyocytes. Therefore, the phytoestrogen from plants has been considered as another potential treatment for heart failure. It has been reported that the natural compound anthocyanin (ACN) has the ability to reduce the risk of cardiovascular disease (CVD). Here, we demonstrated that anthocyanin acts as a cardioprotective drug against doxorubicin-induced heart failure by attenuating cardiac apoptosis via estrogen receptors to stabilize HSF1 expression and down regulated IGF-IIR-induced cardiomyocyte apoptosis. PMID- 27657061 TI - Involvement of Ca2+ Signaling in the Synergistic Effects between Muscarinic Receptor Antagonists and beta2-Adrenoceptor Agonists in Airway Smooth Muscle. AB - Long-acting muscarinic antagonists (LAMAs) and short-acting beta2-adrenoceptor agonists (SABAs) play important roles in remedy for COPD. To propel a translational research for development of bronchodilator therapy, synergistic effects between SABAs with LAMAs were examined focused on Ca2+ signaling using simultaneous records of isometric tension and F340/F380 in fura-2-loaded tracheal smooth muscle. Glycopyrronium (3 nM), a LAMA, modestly reduced methacholine (1 MUM)-induced contraction. When procaterol, salbutamol and SABAs were applied in the presence of glycopyrronium, relaxant effects of these SABAs are markedly enhanced, and percent inhibition of tension was much greater than the sum of those for each agent and those expected from the BI theory. In contrast, percent inhibition of F340/F380 was not greater than those values. Bisindolylmaleimide, an inhibitor of protein kinase C (PKC), significantly increased the relaxant effect of LAMA without reducing F340/F380. Iberiotoxin, an inhibitor of large conductance Ca2+-activated K+ (KCa) channels, significantly suppressed the effects of these combined agents with reducing F340/F380. In conclusion, combination of SABAs with LAMAs synergistically enhances inhibition of muscarinic contraction via decreasing both Ca2+ sensitization mediated by PKC and Ca2+ dynamics mediated by KCa channels. PKC and KCa channels may be molecular targets for cross talk between beta2-adrenoceptors and muscarinic receptors. PMID- 27657064 TI - Potential Seasonal Terrestrial Water Storage Monitoring from GPS Vertical Displacements: A Case Study in the Lower Three-Rivers Headwater Region, China. AB - This study uses the observed vertical displacements of Global Positioning System (GPS) time series obtained from the Crustal Movement Observation Network of China (CMONOC) with careful pre- and post-processing to estimate the seasonal crustal deformation in response to the hydrological loading in lower three-rivers headwater region of southwest China, followed by inferring the annual EWH changes through geodetic inversion methods. The Helmert Variance Component Estimation (HVCE) and the Minimum Mean Square Error (MMSE) criterion were successfully employed. The GPS inferred EWH changes agree well qualitatively with the Gravity Recovery and Climate Experiment (GRACE)-inferred and the Global Land Data Assimilation System (GLDAS)-inferred EWH changes, with a discrepancy of 3.2-3.9 cm and 4.8-5.2 cm, respectively. In the research areas, the EWH changes in the Lancang basin is larger than in the other regions, with a maximum of 21.8-24.7 cm and a minimum of 3.1-6.9 cm. PMID- 27657065 TI - Spatial Ecology of Estuarine Crocodile (Crocodylus porosus) Nesting in a Fragmented Landscape. AB - The role that oil palm plays in the Lower Kinabatangan region of Eastern Sabah is of considerable scientific and conservation interest, providing a model habitat for many tropical regions as they become increasingly fragmented. Crocodilians, as apex predators, widely distributed throughout the tropics, are ideal indicator species for ecosystem health. Drones (or unmanned aerial vehicles (UAVs)) were used to identify crocodile nests in a fragmented landscape. Flights were targeted through the use of fuzzy overlay models and nests located primarily in areas indicated as suitable habitat. Nests displayed a number of similarities in terms of habitat characteristics allowing for refined modelling of survey locations. As well as being more cost-effective compared to traditional methods of nesting survey, the use of drones also enabled a larger survey area to be completed albeit with a limited number of flights. The study provides a methodology for targeted nest surveying, as well as a low-cost repeatable flight methodology. This approach has potential for widespread applicability across a range of species and for a variety of study designs. PMID- 27657066 TI - FGG-NUFFT-Based Method for Near-Field 3-D Imaging Using Millimeter Waves. AB - In this paper, to deal with the concealed target detection problem, an accurate and efficient algorithm for near-field millimeter wave three-dimensional (3-D) imaging is proposed that uses a two-dimensional (2-D) plane antenna array. First, a two-dimensional fast Fourier transform (FFT) is performed on the scattered data along the antenna array plane. Then, a phase shift is performed to compensate for the spherical wave effect. Finally, fast Gaussian gridding based nonuniform FFT (FGG-NUFFT) combined with 2-D inverse FFT (IFFT) is performed on the nonuniform 3 D spatial spectrum in the frequency wavenumber domain to achieve 3-D imaging. The conventional method for near-field 3-D imaging uses Stolt interpolation to obtain uniform spatial spectrum samples and performs 3-D IFFT to reconstruct a 3-D image. Compared with the conventional method, our FGG-NUFFT based method is comparable in both efficiency and accuracy in the full sampled case and can obtain more accurate images with less clutter and fewer noisy artifacts in the down-sampled case, which are good properties for practical applications. Both simulation and experimental results demonstrate that the FGG-NUFFT-based near field 3-D imaging algorithm can have better imaging performance than the conventional method for down-sampled measurements. PMID- 27657067 TI - Modeling and Implementation of Multi-Position Non-Continuous Rotation Gyroscope North Finder. AB - Even when the Global Positioning System (GPS) signal is blocked, a rate gyroscope (gyro) north finder is capable of providing the required azimuth reference information to a certain extent. In order to measure the azimuth between the observer and the north direction very accurately, we propose a multi-position non continuous rotation gyro north finding scheme. Our new generalized mathematical model analyzes the elements that affect the azimuth measurement precision and can thus provide high precision azimuth reference information. Based on the gyro's principle of detecting a projection of the earth rotation rate on its sensitive axis and the proposed north finding scheme, we are able to deduct an accurate mathematical model of the gyro outputs against azimuth with the gyro and shaft misalignments. Combining the gyro outputs model and the theory of propagation of uncertainty, some approaches to optimize north finding are provided, including reducing the gyro bias error, constraining the gyro random error, increasing the number of rotation points, improving rotation angle measurement precision, decreasing the gyro and the shaft misalignment angles. According them, a north finder setup is built and the azimuth uncertainty of 18" is obtained. This paper provides systematic theory for analyzing the details of the gyro north finder scheme from simulation to implementation. The proposed theory can guide both applied researchers in academia and advanced practitioners in industry for designing high precision robust north finder based on different types of rate gyroscopes. PMID- 27657068 TI - Research on the Lift-off Effect of Receiving Longitudinal Mode Guided Waves in Pipes Based on the Villari Effect. AB - The magnetostrictive guided wave technology as a non-contact measurement can generate and receive guided waves with a large lift-off distance up to tens of millimeters. However, the lift-off distance of the receiving coil would affect the coupling efficiency from the elastic energy to the electromagnetic energy. In the existing magnetomechanical models, the change of the magnetic field in the air gap was ignored since the permeability of the rod is much greater than that of air. The lift-off distance of the receiving coil will not affect the receiving signals based on these models. However, the experimental phenomenon is in contradiction with these models. To solve the contradiction, the lift-off effect of receiving the longitudinal mode guided waves in pipes is investigated based on the Villari effect. A finite element model of receiving longitudinal guided waves in pipes is obtained based on the Villari effect, which takes into account the magnetic field in the pipe wall and the air zone at the same time. The relation between the amplitude of the induced signals and the radius (lift-off distance) of the receiving coil is obtained, which is verified by experiment. The coupling efficiency of the receiver is a monotonic decline with the lift-off distance increasing. The decay rate of the low frequency wave is slower than the high frequency wave. Additionally, the results show that the rate of change of the magnetic flux in the air zone and in the pipe wall is the same order of magnitude, but opposite. However, the experimental results show that the error of the model in the large lift-off distance is obvious due to the diffusion of the magnetic field in the air, especially for the high frequency guided waves. PMID- 27657069 TI - Maximum Correntropy Unscented Kalman Filter for Spacecraft Relative State Estimation. AB - A new algorithm called maximum correntropy unscented Kalman filter (MCUKF) is proposed and applied to relative state estimation in space communication networks. As is well known, the unscented Kalman filter (UKF) provides an efficient tool to solve the non-linear state estimate problem. However, the UKF usually plays well in Gaussian noises. Its performance may deteriorate substantially in the presence of non-Gaussian noises, especially when the measurements are disturbed by some heavy-tailed impulsive noises. By making use of the maximum correntropy criterion (MCC), the proposed algorithm can enhance the robustness of UKF against impulsive noises. In the MCUKF, the unscented transformation (UT) is applied to obtain a predicted state estimation and covariance matrix, and a nonlinear regression method with the MCC cost is then used to reformulate the measurement information. Finally, the UT is adopted to the measurement equation to obtain the filter state and covariance matrix. Illustrative examples demonstrate the superior performance of the new algorithm. PMID- 27657070 TI - A Novel Passive Wireless Sensor for Concrete Humidity Monitoring. AB - This paper presents a passive wireless humidity sensor for concrete monitoring. After discussing the transmission of electromagnetic wave in concrete, a novel architecture of wireless humidity sensor, based on Ultra-High Frequency (UHF) Radio Frequency Identification (RFID) technology, is proposed for low-power application. The humidity sensor utilizes the top metal layer to form the interdigitated electrodes, which were then filled with polyimide as the humidity sensing layer. The sensor interface converts the humidity capacitance into a digital signal in the frequency domain. A two-stage rectifier adopts a dynamic bias-voltage generator to boost the effective gate-source voltage of the switches in differential-drive architecture. The clock generator employs a novel structure to reduce the internal voltage swing. The measurement results show that our proposed wireless humidity can achieve a high linearity with a normalized sensitivity of 0.55% %RH at 20 degrees C. Despite the high losses of concrete, the proposed wireless humidity sensor achieves reliable communication performances in passive mode. The maximum operating distance is 0.52 m when the proposed wireless sensor is embedded into the concrete at the depth of 8 cm. The measured results are highly consistent with the results measured by traditional methods. PMID- 27657071 TI - Combating QR-Code-Based Compromised Accounts in Mobile Social Networks. AB - Cyber Physical Social Sensing makes mobile social networks (MSNs) popular with users. However, such attacks are rampant as malicious URLs are spread covertly through quick response (QR) codes to control compromised accounts in MSNs to propagate malicious messages. Currently, there are generally two types of methods to identify compromised accounts in MSNs: one type is to analyze the potential threats on wireless access points and the potential threats on handheld devices' operation systems so as to stop compromised accounts from spreading malicious messages; the other type is to apply the method of detecting compromised accounts in online social networks to MSNs. The above types of methods above focus neither on the problems of MSNs themselves nor on the interaction of sensors' messages, which leads to the restrictiveness of platforms and the simplification of methods. In order to stop the spreading of compromised accounts in MSNs effectively, the attacks have to be traced to their sources first. Through sensors, users exchange information in MSNs and acquire information by scanning QR codes. Therefore, analyzing the traces of sensor-related information helps to identify the compromised accounts in MSNs. This paper analyzes the diversity of information sending modes of compromised accounts and normal accounts, analyzes the regularity of GPS (Global Positioning System)-based location information, and introduces the concepts of entropy and conditional entropy so as to construct an entropy-based model based on machine learning strategies. To achieve the goal, about 500,000 accounts of Sina Weibo and about 100 million corresponding messages are collected. Through the validation, the accuracy rate of the model is proved to be as high as 87.6%, and the false positive rate is only 3.7%. Meanwhile, the comparative experiments of the feature sets prove that sensor-based location information can be applied to detect the compromised accounts in MSNs. PMID- 27657072 TI - Fabrication of Micro-Needle Electrodes for Bio-Signal Recording by a Magnetization-Induced Self-Assembly Method. AB - Micro-needle electrodes (MEs) have attracted more and more attention for monitoring physiological electrical signals, including electrode-skin interface impedance (EII), electromyography (EMG) and electrocardiography (ECG) recording. A magnetization-induced self-assembling method (MSM) was developed to fabricate a microneedle array (MA). A MA coated with Ti/Au film was assembled as a ME. The fracture and insertion properties of ME were tested by experiments. The bio signal recording performance of the ME was measured and compared with a typical commercial wet electrode (Ag/AgCl electrode). The results show that the MA self assembled from the magnetic droplet array under the sum of gravitational surface tension and magnetic potential energies. The ME had good toughness and could easily pierce rabbit skin without being broken or buckling. When the compression force applied on the ME was larger than 2 N, ME could stably record EII, which was a lower value than that measured by Ag/AgCl electrodes. EMG signals collected by ME varied along with the contraction of biceps brachii muscle. ME could record static ECG signals with a larger amplitude and dynamic ECG signals with more distinguishable features in comparison with a Ag/AgCl electrode, therefore, ME is an alternative electrode for bio-signal monitoring in some specific situations. PMID- 27657073 TI - A Security Mechanism for Cluster-Based WSN against Selective Forwarding. AB - A wireless sensor network (WSN) faces a number of outsider and insider attacks, and it is difficult to detect and defend against insider attacks. In particular, an insider selective-forwarding attack, in which the attackers select some of the received packets to drop, most threatens a WSN. Compared to a distributed WSN, a cluster-based WSN will suffer more losses, even the whole network's destruction, if the cluster head is attacked. In this paper, a scheme solving the above issues is proposed with three types of nodes, the Cluster Head (CH), the Inspector Node (IN) and Member Nodes (MNs). The IN monitors the CH's transmission to protect the cluster against a selective-forwarding attack; the CH forwards packets from MNs and other CHs, and randomly checks the IN to ascertain if it works properly; and the MNs send the gathered data packets to the CH and evaluate the behaviors of the CH and IN based on their own reputation mechanism. The novelty of our scheme is that in order to take both the safety and the lifespan of a network into consideration, the composite reputation value (CRV) including forwarding rate, detecting malicious nodes, and surplus energy of the node is utilized to select CH and IN under the new suggested network arrangement, and the use of a node's surplus energy can balance the energy consumption of a node, thereby prolonging the network lifespan. Theoretical analysis and simulation results indicate that the proposed scheme can detect the malicious node accurately and efficiently, so the false alarm rate is lowered by 25.7% compared with Watchdog and the network lifespan is prolonged by 54.84% compared with LEACH (Low Energy Adaptive Clustering Hierarchy). PMID- 27657074 TI - A Laser Line Auto-Scanning System for Underwater 3D Reconstruction. AB - In this study, a laser line auto-scanning system was designed to perform underwater close-range 3D reconstructions with high accuracy and resolution. The system changes the laser plane direction with a galvanometer to perform automatic scanning and obtain continuous laser strips for underwater 3D reconstruction. The system parameters were calibrated with the homography constraints between the target plane and image plane. A cost function was defined to optimize the galvanometer's rotating axis equation. Compensation was carried out for the refraction of the incident and emitted light at the interface. The accuracy and the spatial measurement capability of the system were tested and analyzed with standard balls under laboratory underwater conditions, and the 3D surface reconstruction for a sealing cover of an underwater instrument was proved to be satisfactory. PMID- 27657075 TI - Increasing the Lifetime of Mobile WSNs via Dynamic Optimization of Sensor Node Communication Activity. AB - In this paper, a simple and flexible method for increasing the lifetime of fixed or mobile wireless sensor networks is proposed. Based on past residual energy information reported by the sensor nodes, the sink node or another central node dynamically optimizes the communication activity levels of the sensor nodes to save energy without sacrificing the data throughput. The activity levels are defined to represent portions of time or time-frequency slots in a frame, during which the sensor nodes are scheduled to communicate with the sink node to report sensory measurements. Besides node mobility, it is considered that sensors' batteries may be recharged via a wireless power transmission or equivalent energy harvesting scheme, bringing to the optimization problem an even more dynamic character. We report large increased lifetimes over the non-optimized network and comparable or even larger lifetime improvements with respect to an idealized greedy algorithm that uses both the real-time channel state and the residual energy information. PMID- 27657076 TI - Design of Highly Selective Gas Sensors via Physicochemical Modification of Oxide Nanowires: Overview. AB - Strategies for the enhancement of gas sensing properties, and specifically the improvement of gas selectivity of metal oxide semiconductor nanowire (NW) networks grown by chemical vapor deposition and thermal evaporation, are reviewed. Highly crystalline NWs grown by vapor-phase routes have various advantages, and thus have been applied in the field of gas sensors over the years. In particular, n-type NWs such as SnO2, ZnO, and In2O3 are widely studied because of their simple synthetic preparation and high gas response. However, due to their usually high responses to C2H5OH and NO2, the selective detection of other harmful and toxic gases using oxide NWs remains a challenging issue. Various strategies-such as doping/loading of noble metals, decorating/doping of catalytic metal oxides, and the formation of core-shell structures-have been explored to enhance gas selectivity and sensitivity, and are discussed herein. Additional methods such as the transformation of n-type into p-type NWs and the formation of catalyst-doped hierarchical structures by branch growth have also proven to be promising for the enhancement of gas selectivity. Accordingly, the physicochemical modification of oxide NWs via various methods provides new strategies to achieve the selective detection of a specific gas, and after further investigations, this approach could pave a new way in the field of NW based semiconductor-type gas sensors. PMID- 27657077 TI - Features of a Self-Mixing Laser Diode Operating Near Relaxation Oscillation. AB - When a fraction of the light reflected by an external cavity re-enters the laser cavity, both the amplitude and the frequency of the lasing field can be modulated. This phenomenon is called the self-mixing effect (SME). A self-mixing laser diode (SM-LD) is a sensor using the SME. Usually, such LDs operate below the stability boundary where no relaxation oscillation happens. The boundary is determined by the operation condition including the injection current, optical feedback strength and external cavity length. This paper discovers the features of an SM-LD where the LD operates beyond the stability boundary, that is, near the relaxation oscillation (RO) status. We call the signals from such a SM-LD as RO-SM signals to differentiate them from the conventional SM signals reported in the literature. Firstly, simulations are made based on the well-known Lang and Kobayashi (L-K) equations. Then the experiments are conducted on different LDs to verify the simulation results. It shows that a RO-SM signal exhibits high frequency oscillation with its amplitude modulated by a slow time varying envelop which corresponds to the movement of the external target. The envelope has same fringe structure (half-wavelength displacement resolution) with the conventional SM signals. However, the amplitudes of the RO-SM signals are much higher compared to conventional SM signals. The results presented reveal that an SM-LD operating near the RO has potential for achieving sensing with improved sensitivity. PMID- 27657079 TI - A Portable Laser Photoacoustic Methane Sensor Based on FPGA. AB - A portable laser photoacoustic sensor for methane (CH4) detection based on a field-programmable gate array (FPGA) is reported. A tunable distributed feedback (DFB) diode laser in the 1654 nm wavelength range is used as an excitation source. The photoacoustic signal processing was implemented by a FPGA device. A small resonant photoacoustic cell is designed. The minimum detection limit (1sigma) of 10 ppm for methane is demonstrated. PMID- 27657080 TI - Underdetermined DOA Estimation Using MVDR-Weighted LASSO. AB - The direction of arrival (DOA) estimation problem is formulated in a compressive sensing (CS) framework, and an extended array aperture is presented to increase the number of degrees of freedom of the array. The ordinary least square adaptable least absolute shrinkage and selection operator (OLS A-LASSO) is applied for the first time for DOA estimation. Furthermore, a new LASSO algorithm, the minimum variance distortionless response (MVDR) A-LASSO, which solves the DOA problem in the CS framework, is presented. The proposed algorithm does not depend on the singular value decomposition nor on the orthogonality of the signal and the noise subspaces. Hence, the DOA estimation can be done without a priori knowledge of the number of sources. The proposed algorithm can estimate up to ( ( M 2 - 2 ) / 2 + M - 1 ) / 2 sources using M sensors without any constraints or assumptions about the nature of the signal sources. Furthermore, the proposed algorithm exhibits performance that is superior compared to that of the classical DOA estimation methods, especially for low signal to noise ratios (SNR), spatially-closed sources and coherent scenarios. PMID- 27657078 TI - Zwitterionic Surfactant Modified Acetylene Black Paste Electrode for Highly Facile and Sensitive Determination of Tetrabromobisphenol A. AB - A electrochemical sensor for the highly sensitive detection of tetrabromobisphenol A (TBBPA) was fabricated based on acetylene black paste electrode (ABPE) modified with 3-(N,N-Dimethylpalmitylammonio) propanesulfonate (SB3-16) in this study. The peak current of TBBPA was significantly enhanced at SB3-16/ABPE compared with unmodified electrodes. To further improve the electrochemical performance of the modified electrode, corresponding experimental parameters such as the length of hydrophobic chains of zwitterionic surfactant, the concentration of SB3-16, pH value, and accumulation time were examined. The peak currents of TBBPA were found to be linearly correlated with its concentrations in the range of 1 nM to 1 uM, with a detection limit of 0.4 nM. Besides, a possible mechanism was also discussed, and the hydrophobic interaction between TBBPA and the surfactants was suggested to take a leading role in enhancing the responses. Finally, this sensor was successfully employed to detect TBBPA in water samples. PMID- 27657081 TI - Collection and Processing of Data from Wrist Wearable Devices in Heterogeneous and Multiple-User Scenarios. AB - Over recent years, we have witnessed the development of mobile and wearable technologies to collect data from human vital signs and activities. Nowadays, wrist wearables including sensors (e.g., heart rate, accelerometer, pedometer) that provide valuable data are common in market. We are working on the analytic exploitation of this kind of data towards the support of learners and teachers in educational contexts. More precisely, sleep and stress indicators are defined to assist teachers and learners on the regulation of their activities. During this development, we have identified interoperability challenges related to the collection and processing of data from wearable devices. Different vendors adopt specific approaches about the way data can be collected from wearables into third party systems. This hinders such developments as the one that we are carrying out. This paper contributes to identifying key interoperability issues in this kind of scenario and proposes guidelines to solve them. Taking into account these topics, this work is situated in the context of the standardization activities being carried out in the Internet of Things and Machine to Machine domains. PMID- 27657083 TI - Optimization of Stripping Voltammetric Sensor by a Back Propagation Artificial Neural Network for the Accurate Determination of Pb(II) in the Presence of Cd(II). AB - An easy, but effective, method has been proposed to detect and quantify the Pb(II) in the presence of Cd(II) based on a Bi/glassy carbon electrode (Bi/GCE) with the combination of a back propagation artificial neural network (BP-ANN) and square wave anodic stripping voltammetry (SWASV) without further electrode modification. The effects of Cd(II) in different concentrations on stripping responses of Pb(II) was studied. The results indicate that the presence of Cd(II) will reduce the prediction precision of a direct calibration model. Therefore, a two-input and one-output BP-ANN was built for the optimization of a stripping voltammetric sensor, which considering the combined effects of Cd(II) and Pb(II) on the SWASV detection of Pb(II) and establishing the nonlinear relationship between the stripping peak currents of Pb(II) and Cd(II) and the concentration of Pb(II). The key parameters of the BP-ANN and the factors affecting the SWASV detection of Pb(II) were optimized. The prediction performance of direct calibration model and BP-ANN model were tested with regard to the mean absolute error (MAE), root mean square error (RMSE), average relative error (ARE), and correlation coefficient. The results proved that the BP-ANN model exhibited higher prediction accuracy than the direct calibration model. Finally, a real samples analysis was performed to determine trace Pb(II) in some soil specimens with satisfactory results. PMID- 27657082 TI - Intensity-Stabilized Fast-Scanned Direct Absorption Spectroscopy Instrumentation Based on a Distributed Feedback Laser with Detection Sensitivity down to 4 * 10 6. AB - A novel, intensity-stabilized, fast-scanned, direct absorption spectroscopy (IS FS-DAS) instrumentation, based on a distributed feedback (DFB) diode laser, is developed. A fiber-coupled polarization rotator and a fiber-coupled polarizer are used to stabilize the intensity of the laser, which significantly reduces its relative intensity noise (RIN). The influence of white noise is reduced by fast scanning over the spectral feature (at 1 kHz), followed by averaging. By combining these two noise-reducing techniques, it is demonstrated that direct absorption spectroscopy (DAS) can be swiftly performed down to a limit of detection (LOD) (1sigma) of 4 * 10-6, which opens up a number of new applications. PMID- 27657084 TI - Markov Task Network: A Framework for Service Composition under Uncertainty in Cyber-Physical Systems. AB - In novel collaborative systems, cooperative entities collaborate services to achieve local and global objectives. With the growing pervasiveness of cyber physical systems, however, such collaboration is hampered by differences in the operations of the cyber and physical objects, and the need for the dynamic formation of collaborative functionality given high-level system goals has become practical. In this paper, we propose a cross-layer automation and management model for cyber-physical systems. This models the dynamic formation of collaborative services pursuing laid-down system goals as an ontology-oriented hierarchical task network. Ontological intelligence provides the semantic technology of this model, and through semantic reasoning, primitive tasks can be dynamically composed from high-level system goals. In dealing with uncertainty, we further propose a novel bridge between hierarchical task networks and Markov logic networks, called the Markov task network. This leverages the efficient inference algorithms of Markov logic networks to reduce both computational and inferential loads in task decomposition. From the results of our experiments, high-precision service composition under uncertainty can be achieved using this approach. PMID- 27657085 TI - Efficient Data Gathering Methods in Wireless Sensor Networks Using GBTR Matrix Completion. AB - To obtain efficient data gathering methods for wireless sensor networks (WSNs), a novel graph based transform regularized (GBTR) matrix completion algorithm is proposed. The graph based transform sparsity of the sensed data is explored, which is also considered as a penalty term in the matrix completion problem. The proposed GBTR-ADMM algorithm utilizes the alternating direction method of multipliers (ADMM) in an iterative procedure to solve the constrained optimization problem. Since the performance of the ADMM method is sensitive to the number of constraints, the GBTR-A2DM2 algorithm obtained to accelerate the convergence of GBTR-ADMM. GBTR-A2DM2 benefits from merging two constraint conditions into one as well as using a restart rule. The theoretical analysis shows the proposed algorithms obtain satisfactory time complexity. Extensive simulation results verify that our proposed algorithms outperform the state of the art algorithms for data collection problems in WSNs in respect to recovery accuracy, convergence rate, and energy consumption. PMID- 27657086 TI - Electronic Nose Testing Procedure for the Definition of Minimum Performance Requirements for Environmental Odor Monitoring. AB - Despite initial enthusiasm towards electronic noses and their possible application in different fields, and quite a lot of promising results, several criticalities emerge from most published research studies, and, as a matter of fact, the diffusion of electronic noses in real-life applications is still very limited. In general, a first step towards large-scale-diffusion of an analysis method, is standardization. The aim of this paper is describing the experimental procedure adopted in order to evaluate electronic nose performances, with the final purpose of establishing minimum performance requirements, which is considered to be a first crucial step towards standardization of the specific case of electronic nose application for environmental odor monitoring at receptors. Based on the experimental results of the performance testing of a commercialized electronic nose type with respect to three criteria (i.e., response invariability to variable atmospheric conditions, instrumental detection limit, and odor classification accuracy), it was possible to hypothesize a logic that could be adopted for the definition of minimum performance requirements, according to the idea that these are technologically achievable. PMID- 27657087 TI - Digital Platform for Wafer-Level MEMS Testing and Characterization Using Electrical Response. AB - The uniqueness of microelectromechanical system (MEMS) devices, with their multiphysics characteristics, presents some limitations to the borrowed test methods from traditional integrated circuits (IC) manufacturing. Although some improvements have been performed, this specific area still lags behind when compared to the design and manufacturing competencies developed over the last decades by the IC industry. A complete digital solution for fast testing and characterization of inertial sensors with built-in actuation mechanisms is presented in this paper, with a fast, full-wafer test as a leading ambition. The full electrical approach and flexibility of modern hardware design technologies allow a fast adaptation for other physical domains with minimum effort. The digital system encloses a processor and the tailored signal acquisition, processing, control, and actuation hardware control modules, capable of the structure position and response analysis when subjected to controlled actuation signals in real time. The hardware performance, together with the simplicity of the sequential programming on a processor, results in a flexible and powerful tool to evaluate the newest and fastest control algorithms. The system enables measurement of resonant frequency (Fr), quality factor (Q), and pull-in voltage (Vpi) within 1.5 s with repeatability better than 5 ppt (parts per thousand). A full-wafer with 420 devices under test (DUTs) has been evaluated detecting the faulty devices and providing important design specification feedback to the designers. PMID- 27657088 TI - Design and Implementation of Sound Searching Robots in Wireless Sensor Networks. AB - A sound target-searching robot system which includes a 4-channel microphone array for sound collection, magneto-resistive sensor for declination measurement, and a wireless sensor networks (WSN) for exchanging information is described. It has an embedded sound signal enhancement, recognition and location method, and a sound searching strategy based on a digital signal processor (DSP). As the wireless network nodes, three robots comprise the WSN a personal computer (PC) in order to search the three different sound targets in task-oriented collaboration. The improved spectral subtraction method is used for noise reduction. As the feature of audio signal, Mel-frequency cepstral coefficient (MFCC) is extracted. Based on the K-nearest neighbor classification method, we match the trained feature template to recognize sound signal type. This paper utilizes the improved generalized cross correlation method to estimate time delay of arrival (TDOA), and then employs spherical-interpolation for sound location according to the TDOA and the geometrical position of the microphone array. A new mapping has been proposed to direct the motor to search sound targets flexibly. As the sink node, the PC receives and displays the result processed in the WSN, and it also has the ultimate power to make decision on the received results in order to improve their accuracy. The experiment results show that the designed three-robot system implements sound target searching function without collisions and performs well. PMID- 27657089 TI - A Small Range Six-Axis Accelerometer Designed with High Sensitivity DCB Elastic Element. AB - This paper describes a small range six-axis accelerometer (the measurement range of the sensor is +/-g) with high sensitivity DCB (Double Cantilever Beam) elastic element. This sensor is developed based on a parallel mechanism because of the reliability. The accuracy of sensors is affected by its sensitivity characteristics. To improve the sensitivity, a DCB structure is applied as the elastic element. Through dynamic analysis, the dynamic model of the accelerometer is established using the Lagrange equation, and the mass matrix and stiffness matrix are obtained by a partial derivative calculation and a conservative congruence transformation, respectively. By simplifying the structure of the accelerometer, a model of the free vibration is achieved, and the parameters of the sensor are designed based on the model. Through stiffness analysis of the DCB structure, the deflection curve of the beam is calculated. Compared with the result obtained using a finite element analysis simulation in ANSYS Workbench, the coincidence rate of the maximum deflection is 89.0% along the x-axis, 88.3% along the y-axis and 87.5% along the z-axis. Through strain analysis of the DCB elastic element, the sensitivity of the beam is obtained. According to the experimental result, the accuracy of the theoretical analysis is found to be 90.4% along the x-axis, 74.9% along the y-axis and 78.9% along the z-axis. The measurement errors of linear accelerations ax, ay and az in the experiments are 2.6%, 0.6% and 1.31%, respectively. The experiments prove that accelerometer with DCB elastic element performs great sensitive and precision characteristics. PMID- 27657090 TI - Biomimetic Precapillary Flow Patterns for Enhancing Blood Plasma Separation: A Preliminary Study. AB - In this study, a biomimetic microfluidic plasma separation device is discussed. The design of the device drew inspiration from in vivo observations of enhanced cell-free layer (CFL) formation downstream of vascular bifurcations. The working principle for the plasma separation was based on the plasma skimming effect in an arteriolar bifurcation, which is modulated by CFL formation. The enhancement of the CFL width was achieved by a local hematocrit reduction near the collection channel by creating an uneven hematocrit distribution at the bifurcation of the channel. The device demonstrated a high purity of separation (~99.9%) at physiological levels of hematocrit (~40%). PMID- 27657091 TI - Small Moving Vehicle Detection in a Satellite Video of an Urban Area. AB - Vehicle surveillance of a wide area allows us to learn much about the daily activities and traffic information. With the rapid development of remote sensing, satellite video has become an important data source for vehicle detection, which provides a broader field of surveillance. The achieved work generally focuses on aerial video with moderately-sized objects based on feature extraction. However, the moving vehicles in satellite video imagery range from just a few pixels to dozens of pixels and exhibit low contrast with respect to the background, which makes it hard to get available appearance or shape information. In this paper, we look into the problem of moving vehicle detection in satellite imagery. To the best of our knowledge, it is the first time to deal with moving vehicle detection from satellite videos. Our approach consists of two stages: first, through foreground motion segmentation and trajectory accumulation, the scene motion heat map is dynamically built. Following this, a novel saliency based background model which intensifies moving objects is presented to segment the vehicles in the hot regions. Qualitative and quantitative experiments on sequence from a recent Skybox satellite video dataset demonstrates that our approach achieves a high detection rate and low false alarm simultaneously. PMID- 27657094 TI - Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments. AB - Fucosylated chondroitin sulfate (fCS) from sea cucumber Isostichopus badionotus (fCS-Ib) with a chondroitin sulfate type E (CSE) backbone and 2,4-O-sulfo fucose branches has shown excellent anticoagulant activity although has also show severe adverse effects. Depolymerization represents an effective method to diminish this polysaccharide's side effects. The present study reports a modified controlled Fenton system for degradation of fCS-Ib and the anticoagulant activity of the resulting fragments. Monosaccharides and nuclear magnetic resonance (NMR) analysis of the resulting fragments indicate that no significant chemical changes in the backbone of fCS-Ib and no loss of sulfate groups take place during depolymerization. A reduction in the molecular weight of fCS-Ib should result in a dramatic decrease in prolonging activated partial thromboplastin time and thrombin time. A decrease in the inhibition of thrombin (FIIa) by antithromin III (AT III) and heparin cofactor II (HCII), and the slight decrease of the inhibition of factor X activity, results in a significant increase of anti-factor Xa (FXa)/anti-FIIa activity ratio. The modified free-radical depolymerization method enables preparation of glycosaminoglycan (GAG) oligosaccharides suitable for investigation of clinical anticoagulant application. PMID- 27657093 TI - Molecular Weight-Dependent Immunostimulative Activity of Low Molecular Weight Chitosan via Regulating NF-kappaB and AP-1 Signaling Pathways in RAW264.7 Macrophages. AB - Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been found to possess many important biological properties, such as antioxidant and antitumor effects. In our previous study, LMWCs were found to elicit a strong immunomodulatory response in macrophages dependent on molecular weight. Herein we further investigated the molecular weight-dependent immunostimulative activity of LMWCs and elucidated its mechanism of action on RAW264.7 macrophages. LMWCs (3 kDa and 50 kDa of molecular weight) could significantly enhance the mRNA expression levels of COX-2, IL-10 and MCP-1 in a molecular weight and concentration-dependent manner. The results suggested that LMWCs elicited a significant immunomodulatory response, which was dependent on the dose and the molecular weight. Regarding the possible molecular mechanism of action, LMWCs promoted the expression of the genes of key molecules in NF-kappaB and AP-1 pathways, including IKKbeta, TRAF6 and JNK1, and induced the phosphorylation of protein IKBalpha in RAW264.7 macrophage. Moreover, LMWCs increased nuclear translocation of p65 and activation of activator protein-1 (AP-1, C-Jun and C Fos) in a molecular weight-dependent manner. Taken together, our findings suggested that LMWCs exert immunostimulative activity via activation of NF-kappaB and AP-1 pathways in RAW264.7 macrophages in a molecular weight-dependent manner and that 3 kDa LMWC shows great potential as a novel agent for the treatment of immune suppression diseases and in future vaccines. PMID- 27657095 TI - Acute Toxicity and Ecological Risk Assessment of Benzophenone and N,N-Diethyl-3 Methylbenzamide in Personal Care Products. AB - Benzophenone (BP) and N,N-diethyl-3-methylbenzamide (DEET) are two chemicals often used in personal care products (PCPs). There is a lack of systematic ecotoxicological evaluations about the two chemicals to aquatic organisms. In the present study, the acute toxic effects on Chlorella vulgaris, Daphnia Magana, and Brachydanio rerio were tested and the ecotoxicological risks were evaluated. For BP, the 96-h half-maximal effective concentration (EC50) on C. vulgaris was 6.86 mg/L; the 24-h median lethal concentration (LC50) on D. magana was 7.63 mg/L; the 96-h LC50 on B. rerio was 14.73 mg/L. For DEET, those were 270.72 mg/L, 40.74 mg/L, and 109.67 mg/L, respectively. The mixture toxicity of BP and DEET, on C. vulgaris, D. magana, and B. rerio all showed an additive effect. The induced predicted no-effect concentrations (PNECs) for BP and DEET by assessment factor (AF) method are 0.003 mg/L and 0.407 mg/L, respectively. Both are lower than the concentrations detected from environment at present, verifying that BP and DEET are low-risk chemicals to the environment. PMID- 27657092 TI - Antimicrobial Peptides Targeting Gram-Positive Bacteria. AB - Antimicrobial peptides (AMPs) have remarkably different structures as well as biological activity profiles, whereupon most of these peptides are supposed to kill bacteria via membrane damage. In order to understand their molecular mechanism and target cell specificity for Gram-positive bacteria, it is essential to consider the architecture of their cell envelopes. Before AMPs can interact with the cytoplasmic membrane of Gram-positive bacteria, they have to traverse the cell wall composed of wall- and lipoteichoic acids and peptidoglycan. While interaction of AMPs with peptidoglycan might rather facilitate penetration, interaction with anionic teichoic acids may act as either a trap for AMPs or a ladder for a route to the cytoplasmic membrane. Interaction with the cytoplasmic membrane frequently leads to lipid segregation affecting membrane domain organization, which affects membrane permeability, inhibits cell division processes or leads to delocalization of essential peripheral membrane proteins. Further, precursors of cell wall components, especially the highly conserved lipid II, are directly targeted by AMPs. Thereby, the peptides do not inhibit peptidoglycan synthesis via binding to proteins like common antibiotics, but form a complex with the precursor molecule, which in addition can promote pore formation and membrane disruption. Thus, the multifaceted mode of actions will make AMPs superior to antibiotics that act only on one specific target. PMID- 27657096 TI - Return Migrants' Experience of Access to Care in Corrupt Healthcare Systems: The Bosnian Example. AB - Equal and universal access to healthcare services is a core priority for a just health system. A key societal determinant seen to create inequality in access to healthcare is corruption in the healthcare system. How return migrants' access to healthcare is affected by corruption is largely unstudied, even though return migrants may be particularly vulnerable to problems related to corruption due to their period of absence from their country of origin. This article investigates how corruption in the healthcare sector affects access to healthcare for refugees who repatriated to Bosnia, a country with a high level of corruption, from Denmark, a country with a low level of corruption. The study is based on 18 semi structured interviews with 33 refugees who returned after long-term residence in Denmark. We found that the returned refugees faced greater problems with corruption than was the case for those who had not left the country, as doctors considered them to be better endowed financially and therefore demanded larger bribes from them than they did from those who had remained in Bosnia. Moreover, during their stay abroad the returnees had lost the connections that could have helped them sidestep the corruption. Returned refugees are thus particularly vulnerable to the effects of corruption. PMID- 27657097 TI - A Group Decision Framework with Intuitionistic Preference Relations and Its Application to Low Carbon Supplier Selection. AB - This article develops a group decision framework with intuitionistic preference relations. An approach is first devised to rectify an inconsistent intuitionistic preference relation to derive an additive consistent one. A new aggregation operator, the so-called induced intuitionistic ordered weighted averaging (IIOWA) operator, is proposed to aggregate individual intuitionistic fuzzy judgments. By using the mean absolute deviation between the original and rectified intuitionistic preference relations as an order inducing variable, the rectified consistent intuitionistic preference relations are aggregated into a collective preference relation. This treatment is presumably able to assign different weights to different decision-makers' judgments based on the quality of their inputs (in terms of consistency of their original judgments). A solution procedure is then developed for tackling group decision problems with intuitionistic preference relations. A low carbon supplier selection case study is developed to illustrate how to apply the proposed decision model in practice. PMID- 27657098 TI - The Role of Health Co-Benefits in the Development of Australian Climate Change Mitigation Policies. AB - Reducing domestic carbon dioxide and other associated emissions can lead to short term, localized health benefits. Quantifying and incorporating these health co benefits into the development of national climate change mitigation policies may facilitate the adoption of stronger policies. There is, however, a dearth of research exploring the role of health co-benefits on the development of such policies. To address this knowledge gap, research was conducted in Australia involving the analysis of several data sources, including interviews carried out with Australian federal government employees directly involved in the development of mitigation policies. The resulting case study determined that, in Australia, health co-benefits play a minimal role in the development of climate change mitigation policies. Several factors influence the extent to which health co benefits inform the development of mitigation policies. Understanding these factors may help to increase the political utility of future health co-benefits studies. PMID- 27657099 TI - Effects of Rational-Emotive Hospice Care Therapy on Problematic Assumptions, Death Anxiety, and Psychological Distress in a Sample of Cancer Patients and Their Family Caregivers in Nigeria. AB - This study was a preliminary investigation that aimed to examine the effects of rational emotive hospice care therapy (REHCT) on problematic assumptions, death anxiety, and psychological distress in a sample of cancer patients and their family caregivers in Nigeria. The study adopted a pre-posttest randomized control group design. Participants were community-dwelling cancer patients (n = 32) and their family caregivers (n = 52). The treatment process consisted of 10 weeks of full intervention and 4 weeks of follow-up meetings that marked the end of intervention. The study used repeated-measures analysis of variance for data analysis. The findings revealed significant effects of a REHCT intervention program on problematic assumptions, death anxiety, and psychological distress reduction among the cancer patients and their family caregivers at the end of the intervention. The improvements were also maintained at follow-up meetings in the treatment group compared with the control group who received the usual care and conventional counseling. The researchers have been able to show that REHCT intervention is more effective than a control therapy for cancer patients' care, education, and counseling in the Nigerian context. PMID- 27657100 TI - Identifying the Uncertainty in Physician Practice Location through Spatial Analytics and Text Mining. AB - In response to the widespread concern about the adequacy, distribution, and disparity of access to a health care workforce, the correct identification of physicians' practice locations is critical to access public health services. In prior literature, little effort has been made to detect and resolve the uncertainty about whether the address provided by a physician in the survey is a practice address or a home address. This paper introduces how to identify the uncertainty in a physician's practice location through spatial analytics, text mining, and visual examination. While land use and zoning code, embedded within the parcel datasets, help to differentiate resident areas from other types, spatial analytics may have certain limitations in matching and comparing physician and parcel datasets with different uncertainty issues, which may lead to unforeseen results. Handling and matching the string components between physicians' addresses and the addresses of the parcels could identify the spatial uncertainty and instability to derive a more reasonable relationship between different datasets. Visual analytics and examination further help to clarify the undetectable patterns. This research will have a broader impact over federal and state initiatives and policies to address both insufficiency and maldistribution of a health care workforce to improve the accessibility to public health services. PMID- 27657101 TI - Empowering Energy Justice. AB - The U.S. is experiencing unprecedented movement away from coal and, to a lesser degree, oil. Burdened low-income communities and people of color could experience health benefits from reductions in air and water pollution, yet these same groups could suffer harm if transitions lack broad public input or if policies prioritize elite or corporate interests. This paper highlights how U.S. energy transitions build from, and contribute to, environmental injustices. Energy justice requires not only ending disproportionate harm, it also entails involvement in the design of solutions and fair distribution of benefits, such as green jobs and clean air. To what extent does the confluence of state, civic, and market processes assure "just" transitions to clean, low-carbon energy production involving equitable distribution of costs, benefits, and decision-making power? To explore this question we assess trends with (1) fossil fuel divestment; (2) carbon taxes and social cost of carbon measurements; (3) cap-and-trade; (4) renewable energy; and (5) energy efficiency. Current research demonstrates opportunities and pitfalls in each area with mixed or partial energy justice consequences, leading to our call for greater attention to the specifics of distributive justice, procedural justice, and recognition justice in research, policy, and action. Illustrative energy transition case studies suggest the feasibility and benefit of empowering approaches, but also indicate there can be conflict between "green" and "just", as evident though stark inequities in clean energy initiatives. To identify positive pathways forward, we compile priorities for an energy justice research agenda based on interactive and participatory practices aligning advocacy, activism, and academics. PMID- 27657102 TI - Psychometric Properties and Clinical Usefulness of the Youth Self-Report DSM Oriented Scales: A Field Study among Detained Male Adolescents. AB - It is unknown if the DSM-oriented (DSM) scales of the Youth Self-Report (YSR) are useful to determine what kind of narrowly-focused psychiatric assessment is needed, and how well these scales serve as a triage tool in real-world forensic settings. To address this knowledge gap, the YSR and diagnostic interviews were administered to 405 detained boys as part of a clinical protocol. Continuous DSM scale scores (e.g., Conduct Problems) were moderately to highly accurate in predicting their corresponding disorder (e.g., conduct disorder), whereas dichotomized DSM scale scores were not. To test the DSM scales' usefulness for triage purposes, the sensitivity and specificity of being in the borderline range of one or more DSM scales were calculated. Almost all boys who did not have a disorder were in the normal range of at least one DSM scale (high specificity). However, many boys with a disorder would have been missed if such a decision rule was used for triage purposes (low sensitivity). In conclusion, their relations with the corresponding disorders support the construct validity of the DSM scales in an applied forensic setting. Nevertheless, the findings also warrant against the use of these scales for planning further narrowly-focused assessment or for triage purposes. PMID- 27657103 TI - Impact of Heat Wave Definitions on the Added Effect of Heat Waves on Cardiovascular Mortality in Beijing, China. AB - Heat waves are associated with increased mortality, however, few studies have examined the added effect of heat waves. Moreover, there is limited evidence for the influence of different heat wave definitions (HWs) on cardiovascular mortality in Beijing, the capital of China. The aim of this study was to find the best HW definitions for cardiovascular mortality, and we examined the effect modification by an individual characteristic on cardiovascular mortality in Beijing, a typical northern city in China. We applied a Poisson generalized additive approach to estimate the differences in cardiovascular mortality during heat waves (using 12 HWs) compared with non-heat-wave days in Beijing from 2006 to 2009. We also validated the model fit by checking the residuals to ensure that the autocorrelation was successfully removed. In addition, the effect modifications by individual characteristics were explored in different HWs. Our results showed that the associations between heat waves and cardiovascular mortality differed from different HWs. HWs using the 93th percentile of the daily average temperature (27.7 degrees C) and a duration >=5 days had the greatest risk, with an increase of 18% (95% confidence interval (CI): 6%, 31%) in the overall population, 24% (95% CI: 10%, 39%) in an older group (ages >=65 years), and 22% (95% CI: 3%, 44%) in a female group. The added effect of heat waves was apparent after 5 consecutive heat wave days for the overall population and the older group. Females and the elderly were at higher risk than males and younger subjects (ages <65 years). Our findings suggest that heat wave definitions play a significant role in the relationship between heat wave and cardiovascular mortality. Using a suitable definition may have implications for designing local heat early warning systems and protecting the susceptible populations during heat waves. PMID- 27657104 TI - Dust and Cobalt Levels in the Austrian Tungsten Industry: Workplace and Human Biomonitoring Data. AB - In general, routine industrial hygiene (IH) data are collected not to serve for scientific research but to check for compliance with occupational limit values. In the preparation of an occupational retrospective cohort study it is vital to test the validity of the exposure assessment based on incomplete (temporal coverage, departments) IH data. Existing IH data from a large hard metal plant was collected. Individual workers' exposure per year and department was estimated based on linear regression of log-transformed exposure data for dust, tungsten, and cobalt. Estimated data were back-transformed, and for cobalt the validity of the estimates was confirmed by comparison with individual cobalt concentrations in urine. Air monitoring data were available from 1985 to 2012 and urine tests from the years 2008 to 2014. A declining trend and significant differences among departments was evident for all three air pollutants. The estimated time trend fitted the time trend in urine values well. At 1 mg/m3, cobalt in the air leads to an excretion of approximately 200 ug/L cobalt in urine. Cobalt levels in urine were significantly higher in smokers with an interaction effect between smoking and air concentrations. Exposure estimates of individual workers are generally feasible in the examined plant, although some departments are not documented sufficiently enough. Additional information (expert knowledge) is needed to fill these gaps. PMID- 27657105 TI - Acoustic, Visual and Spatial Indicators for the Description of the Soundscape of Waterfront Areas with and without Road Traffic Flow. AB - High flows of road traffic noise in urban agglomerations can negatively affect the livability of squares and parks located at the neighborhood, district and city levels, therefore pushing anyone who wants to enjoy calmer, quieter areas to move to non-urban parks. Due to the distances between these areas, it is not possible to go as regularly as would be necessary to satisfy any needs. Even if cities are densely populated, the presence of a sea or riverfront offers the possibility of large restorative places, or at least with potential features for being the natural core of an urban nucleus after a renewal intervention. This study evaluates the soundscape of the Naples waterfront, presenting an overview of the most significant visual, acoustic and spatial factors related to the pedestrian areas, as well as areas open to road traffic and others where the road traffic is limited. The factors were chosen with feature selection methods and artificial neural networks. The results show how certain factors, such as the perimeter between the water and promenade, the visibility of the sea or the density of green areas, can affect the perception of the soundscape quality in the areas with road traffic. In the pedestrian areas, acoustic factors, such as loudness or the A-weighted sound level exceeded for 10% of the measurement duration (LA10), influence the perceived quality of the soundscape. PMID- 27657107 TI - Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag. AB - Retroviruses specifically package full-length, dimeric genomic RNA (gRNA) even in the presence of a vast excess of cellular RNA. The "psi" (Psi) element within the 5'-untranslated region (5'UTR) of gRNA is critical for packaging through interaction with the nucleocapsid (NC) domain of Gag. However, in vitro Gag binding affinity for Psi versus non-Psi RNAs is not significantly different. Previous salt-titration binding assays revealed that human immunodeficiency virus type 1 (HIV-1) Gag bound to Psi RNA with high specificity and relatively few charge interactions, whereas binding to non-Psi RNA was less specific and involved more electrostatic interactions. The NC domain was critical for specific Psi binding, but surprisingly, a Gag mutant lacking the matrix (MA) domain was less effective at discriminating Psi from non-Psi RNA. We now find that Rous sarcoma virus (RSV) Gag also effectively discriminates RSV Psi from non-Psi RNA in a MA-dependent manner. Interestingly, Gag chimeras, wherein the HIV-1 and RSV MA domains were swapped, maintained high binding specificity to cognate Psi RNAs. Using Psi RNA mutant constructs, determinants responsible for promoting high Gag binding specificity were identified in both systems. Taken together, these studies reveal the functional equivalence of HIV-1 and RSV MA domains in facilitating Psi RNA selectivity by Gag, as well as Psi elements that promote this selectivity. PMID- 27657106 TI - Arms Race between Enveloped Viruses and the Host ERAD Machinery. AB - Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells. PMID- 27657108 TI - Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden. AB - Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose (Alces alces) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar (Sus scrofa) with 21 out of 139 animals (15%), roe deer (Capreolus capreolus) with 2 out of 30 animals, red deer (Cervus elaphus) with 1 out of 15 animals, and fallow deer (Dama dama) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern. PMID- 27657111 TI - Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection. AB - Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments. PMID- 27657109 TI - The Host Cell Receptors for Measles Virus and Their Interaction with the Viral Hemagglutinin (H) Protein. AB - The hemagglutinin (H) protein of measles virus (MeV) interacts with a cellular receptor which constitutes the initial stage of infection. Binding of H to this host cell receptor subsequently triggers the F protein to activate fusion between virus and host plasma membranes. The search for MeV receptors began with vaccine/laboratory virus strains and evolved to more relevant receptors used by wild-type MeV. Vaccine or laboratory strains of measles virus have been adapted to grow in common cell lines such as Vero and HeLa cells, and were found to use membrane cofactor protein (CD46) as a receptor. CD46 is a regulator that normally prevents cells from complement-mediated self-destruction, and is found on the surface of all human cells, with the exception of erythrocytes. Mutations in the H protein, which occur during adaptation and allow the virus to use CD46 as a receptor, have been identified. Wild-type isolates of measles virus cannot use the CD46 receptor. However, both vaccine/laboratory and wild-type strains can use an immune cell receptor called signaling lymphocyte activation molecule family member 1 (SLAMF1; also called CD150) and a recently discovered epithelial receptor known as Nectin-4. SLAMF1 is found on activated B, T, dendritic, and monocyte cells, and is the initial target for infections by measles virus. Nectin 4 is an adherens junction protein found at the basal surfaces of many polarized epithelial cells, including those of the airways. It is also over-expressed on the apical and basal surfaces of many adenocarcinomas, and is a cancer marker for metastasis and tumor survival. Nectin-4 is a secondary exit receptor which allows measles virus to replicate and amplify in the airways, where the virus is expelled from the body in aerosol droplets. The amino acid residues of H protein that are involved in binding to each of the receptors have been identified through X-ray crystallography and site-specific mutagenesis. Recombinant measles "blind" to each of these receptors have been constructed, allowing the virus to selectively infect receptor specific cell lines. Finally, the observations that SLAMF1 is found on lymphomas and that Nectin-4 is expressed on the cell surfaces of many adenocarcinomas highlight the potential of measles virus for oncolytic therapy. Although CD46 is also upregulated on many tumors, it is less useful as a target for cancer therapy, since normal human cells express this protein on their surfaces. PMID- 27657113 TI - Zebra Alphaherpesviruses (EHV-1 and EHV-9): Genetic Diversity, Latency and Co Infections. AB - Alphaherpesviruses are highly prevalent in equine populations and co-infections with more than one of these viruses' strains frequently diagnosed. Lytic replication and latency with subsequent reactivation, along with new episodes of disease, can be influenced by genetic diversity generated by spontaneous mutation and recombination. Latency enhances virus survival by providing an epidemiological strategy for long-term maintenance of divergent strains in animal populations. The alphaherpesviruses equine herpesvirus 1 (EHV-1) and 9 (EHV-9) have recently been shown to cross species barriers, including a recombinant EHV-1 observed in fatal infections of a polar bear and Asian rhinoceros. Little is known about the latency and genetic diversity of EHV-1 and EHV-9, especially among zoo and wild equids. Here, we report evidence of limited genetic diversity in EHV-9 in zebras, whereas there is substantial genetic variability in EHV-1. We demonstrate that zebras can be lytically and latently infected with both viruses concurrently. Such a co-occurrence of infection in zebras suggests that even relatively slow-evolving viruses such as equine herpesviruses have the potential to diversify rapidly by recombination. This has potential consequences for the diagnosis of these viruses and their management in wild and captive equid populations. PMID- 27657110 TI - Orchestrating the Selection and Packaging of Genomic RNA by Retroviruses: An Ensemble of Viral and Host Factors. AB - Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag-Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the cis-acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the cis- and trans-acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison. PMID- 27657112 TI - Transmission of Hepatitis E Virus in Developing Countries. AB - Hepatitis E virus (HEV), an RNA virus of the Hepeviridae family, has marked heterogeneity. While all five HEV genotypes can cause human infections, genotypes HEV-1 and -2 infect humans alone, genotypes HEV-3 and -4 primarily infect pigs, boars and deer, and genotype HEV-7 primarily infects dromedaries. The global distribution of HEV has distinct epidemiological patterns based on ecology and socioeconomic factors. In resource-poor countries, disease presents as large scale waterborne epidemics, and few epidemics have spread through person-to person contact; however, endemic diseases within these countries can potentially spread through person-to-person contact or fecally contaminated water and foods. Vertical transmission of HEV from infected mother to fetus causes high fetal and perinatal mortality. Other means of transmission, such as zoonotic transmission, can fluctuate depending upon the region and strain of the virus. For instance, zoonotic transmission can sometimes play an insignificant role in human infections, such as in India, where human and pig HEV infections are unrelated. However, recently China and Southeast Asia have experienced a zoonotic spread of HEV-4 from pigs to humans and this has become the dominant mode of transmission of hepatitis E in eastern China. Zoonotic HEV infections in humans occur by eating undercooked pig flesh, raw liver, and sausages; through vocational contact; or via pig slurry, which leads to environmental contamination of agricultural products and seafood. Lastly, blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is currently under serious consideration. To summarize, HEV genotypes 1 and 2 cause epidemic and endemic diseases in resource poor countries, primarily spreading through contaminated drinking water. HEV genotypes 3 and 4 on the other hand, cause autochthonous infections in developed, and many developing countries, by means of a unique zoonotic food-borne transmission. PMID- 27657115 TI - Nutrient Intake Is Associated with Longevity Characterization by Metabolites and Element Profiles of Healthy Centenarians. AB - The relationships between diet and metabolites as well as element profiles in healthy centenarians are important but remain inconclusive. Therefore, to test the interesting hypothesis that there would be distinctive features of metabolites and element profiles in healthy centenarians, and that these would be associated with nutrient intake; the short chain fatty acids (SCFAs), total bile acids and ammonia in feces, phenol, p-cresol, uric acid, urea, creatinine and ammonia in urine, and element profiles in fingernails were determined in 90 healthy elderly people, including centenarians from Bama county (China)-a famous longevous region-and elderly people aged 80-99 from the longevous region and a non-longevous region. The partial least squares-discriminant analysis was used for pattern recognition. As a result, the centenarians showed a distinct metabolic pattern. Seven characteristic components closely related to the centenarians were identified, including acetic acid, total SCFA, Mn, Co, propionic acid, butyric acid and valeric acid. Their concentrations were significantly higher in the centenarians group (p < 0.05). Additionally, the dietary fiber intake was positively associated with butyric acid contents in feces (r = 0.896, p < 0.01), and negatively associated with phenol in urine (r = 0.326, p < 0.01). The results suggest that the specific metabolic pattern of centenarians may have an important and positive influence on the formation of the longevity phenomenon. Elevated dietary fiber intake should be a path toward health and longevity. PMID- 27657116 TI - Maternal Dietary Patterns and Gestational Diabetes Mellitus in a Multi-Ethnic Asian Cohort: The GUSTO Study. AB - Gestational Diabetes Mellitus (GDM) is associated with an increased risk of perinatal morbidity and long term health issues for both the mother and offspring. Previous research has demonstrated associations between maternal diet and GDM development, but evidence in Asian populations is limited. The objective of our study was to examine the cross-sectional relationship between maternal dietary patterns during pregnancy and the risk of GDM in a multi-ethnic Asian cohort. Maternal diet was ascertained using 24-h dietary recalls from participants in the Growing up in Singapore towards healthy outcomes (GUSTO) study-a prospective mother-offspring cohort, and GDM was diagnosed according to 1999 World Health Organisation guidelines. Dietary patterns were identified using factor analysis, and multivariate regression analyses performed to assess the association with GDM. Of 909 participants, 17.6% were diagnosed with GDM. Three dietary patterns were identified: a vegetable-fruit-rice-based-diet, a seafood noodle-based-diet and a pasta-cheese-processed-meat-diet. After adjusting for confounding variables, the seafood-noodle-based-diet was associated with a lower likelihood of GDM (Odds Ratio (95% Confidence Interval)) = 0.74 (0.59, 0.93). The dietary pattern found to be associated with GDM in our study was substantially different to those reported previously in Western populations. PMID- 27657114 TI - Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections. AB - Capsid-targeted viral inactivation (CTVI), a conceptually powerful new antiviral strategy, is attracting increasing attention from researchers. Specifically, this strategy is based on fusion between the capsid protein of a virus and a crucial effector molecule, such as a nuclease (e.g., staphylococcal nuclease, Barrase, RNase HI), lipase, protease, or single-chain antibody (scAb). In general, capsid proteins have a major role in viral integration and assembly, and the effector molecule used in CTVI functions to degrade viral DNA/RNA or interfere with proper folding of viral key proteins, thereby affecting the infectivity of progeny viruses. Interestingly, such a capsid-enzyme fusion protein is incorporated into virions during packaging. CTVI is more efficient compared to other antiviral methods, and this approach is promising for antiviral prophylaxis and therapy. This review summarizes the mechanism and utility of CTVI and provides some successful applications of this strategy, with the ultimate goal of widely implementing CTVI in antiviral research. PMID- 27657117 TI - Carbohydrate Mouth Rinsing Enhances High Intensity Time Trial Performance Following Prolonged Cycling. AB - There is good evidence that mouth rinsing with carbohydrate (CHO) solutions can enhance endurance performance (>=30 min). The impact of a CHO mouth rinse on sprint performance has been less consistent, suggesting that CHO may confer benefits in conditions of 'metabolic strain'. To test this hypothesis, the current study examined the impact of late-exercise mouth rinsing on sprint performance. Secondly, we investigated the effects of a protein mouth rinse (PRO) on performance. Eight trained male cyclists participated in three trials consisting of 120 min of constant-load cycling (55% Wmax) followed by a 30 km computer-simulated time trial, during which only water was provided. Following 15 min of muscle function assessment, 10 min of constant-load cycling (3 min at 35% Wmax, 7 min at 55% Wmax) was performed. This was immediately followed by a 2 km time trial. Subjects rinsed with 25 mL of CHO, PRO, or placebo (PLA) at min 5:00 and 14:30 of the 15 min muscle function phase, and min 8:00 of the 10-min constant-load cycling. Magnitude-based inferential statistics were used to analyze the effects of the mouth rinse on 2-km time trial performance and the following physiological parameters: Maximum Voluntary Contract (MVC), Rating of Perceived Exertion (RPE), Heart Rate (HR), and blood glucose levels. The primary finding was that CHO 'likely' enhanced performance vs. PLA (3.8%), whereas differences between PRO and PLA were unclear (0.4%). These data demonstrate that late-race performance is enhanced by a CHO rinse, but not PRO, under challenging metabolic conditions. More data should be acquired before this strategy is recommended for the later stages of cycling competition under more practical conditions, such as when carbohydrates are supplemented throughout the preceding minutes/hours of exercise. PMID- 27657118 TI - The mTORC1-Signaling Pathway and Hepatic Polyribosome Profile Are Enhanced after the Recovery of a Protein Restricted Diet by a Combination of Soy or Black Bean with Corn Protein. AB - Between 6% and 11% of the world's population suffers from malnutrition or undernutrition associated with poverty, aging or long-term hospitalization. The present work examined the effect of different types of proteins on the mechanistic target of rapamycin (mTORC1)-signaling pathway in: (1) healthy; and (2) protein restricted rats. (1) In total, 200 rats were divided into eight groups and fed one of the following diets: 20% casein (C), soy (S), black bean (B), B + Corn (BCr), Pea (P), spirulina (Sp), sesame (Se) or Corn (Cr). Rats fed C or BCr had the highest body weight gain; rats fed BCr had the highest pS6K1/S6K1 ratio; rats fed B, BCr or P had the highest eIF4G expression; (2) In total, 84 rats were fed 0.5% C for 21 day and protein rehabilitated with different proteins. The S, soy + Corn (SCr) and BCr groups had the highest body weight gain. Rats fed SCr and BCr had the highest eIF4G expression and liver polysome formation. These findings suggest that the quality of the dietary proteins modulate the mTORC1-signaling pathway. In conclusion, the combination of BCr or SCr are the best proteins for dietary protein rehabilitation due to the significant increase in body weight, activation of the mTORC1-signaling pathway in liver and muscle, and liver polysome formation. PMID- 27657119 TI - The Mediterranean Diet and Cognitive Function among Healthy Older Adults in a 6 Month Randomised Controlled Trial: The MedLey Study. AB - Evidence from a limited number of randomised controlled intervention trials (RCTs) have shown that a Mediterranean dietary pattern may reduce the risk of cognitive decline and enhance cognitive function among healthy older adults. However, there are currently no data in non-Mediterranean older adult populations. The present study aimed to address this gap by examining the effect of a Mediterranean dietary pattern (MedDiet) for six months on aspects of cognitive function in a randomised controlled intervention trial (the MedLey study) that extended for a duration of 18 months. In the final analysed cohort, a total of 137 men and women (mean age of 72.1 +/- 5.0 years) randomly assigned to either a MedDiet or control diet (HabDiet) (i.e., habitual dietary intake), were assessed on a comprehensive neuropsychological test battery, including 11 individual tests. In multivariable-adjusted models, the MedDiet group did not perform significantly better than the HabDiet control group for executive functioning (adjusted mean differences: +2.53, 95% CI -2.59 to 7.65, p = 0.33); speed of processing (adjusted mean differences: +3.24, 95% CI -1.21 to 7.70, p = 0.15); memory (adjusted mean differences: +2.00, 95% CI -3.88 to 7.88, p = 0.50); visual-spatial ability (adjusted mean differences: +0.21, 95% CI -0.38 to 0.81, 0.48); and overall age-related cognitive performance (adjusted mean differences: +7.99, 95% CI -4.00 to 19.9, p = 0.19). In conclusion, this study did not find evidence of a beneficial effect of a MedDiet intervention on cognitive function among healthy older adults. PMID- 27657120 TI - Fructose Beverage Consumption Induces a Metabolic Syndrome Phenotype in the Rat: A Systematic Review and Meta-Analysis. AB - A high intake of refined carbohydrates, particularly the monosaccharide fructose, has been attributed to the growing epidemics of obesity and type-2 diabetes. Animal studies have helped elucidate the metabolic effects of dietary fructose, however, variations in study design make it difficult to draw conclusions. The aim of this study was to review the effects of fructose beverage consumption on body weight, systolic blood pressure and blood glucose, insulin and triglyceride concentrations in validated rat models. We searched Ovid Embase Classic + EmbaseMedline and Ovid Medline databases and included studies that used adolescent/adult male rats, with fructose beverage consumption for >3 weeks. Data from 26 studies were pooled by an inverse variance weighting method using random effects models, expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Overall, 10%-21% w/v fructose beverage consumption was associated with increased rodent body weight (SMD, 0.62 (95% CI: 0.18, 1.06)), systolic blood pressure (SMD, 2.94 (95% CI: 2.10, 3.77)) and blood glucose (SMD, 0.77 (95% CI: 0.36, 1.19)), insulin (SMD, 2.32 (95% CI: 1.57, 3.07)) and triglyceride (SMD, 1.87 (95% CI: 1.39, 2.34)) concentrations. Therefore, the consumption of a low concentration fructose beverage is sufficient to cause early signs of the metabolic syndrome in adult rats. PMID- 27657121 TI - The Use of Fish Oil with Warfarin Does Not Significantly Affect either the International Normalised Ratio or Incidence of Adverse Events in Patients with Atrial Fibrillation and Deep Vein Thrombosis: A Retrospective Study. AB - BACKGROUND: Warfarin is a leading anticoagulant in the management of atrial fibrillation (AF) and deep vein thrombosis (DVT). Drug interactions influence the safety of warfarin use and while extensive literature exists regarding the effect on warfarin control and bleeding incidence with many medicines, there is little evidence on the influence of complementary medicines. The aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control and bleeding incidence in AF and DVT patients. METHODS: A retrospective analysis was conducted utilising patient information from a large private pathology clinic. AF and DVT patients receiving long-term warfarin therapy (>30 days) at the clinic and taking fish and krill oil supplements were eligible for study inclusion. RESULTS: Of the 2081 patients assessed, a total of 573 warfarin users met the inclusion criteria with 145 patients in the fish and krill oil group (supplement group) and 428 patients in the control group. Overall, it was found that fish and krill oils did not significantly alter warfarin time in therapeutic range (TTR) or bleeding incidence, even when compared by gender. CONCLUSION: Omega-3 supplementation with fish and krill oil does not significantly affect long-term warfarin control and bleeding and thromboembolic events when consumed concurrently in patients managed at an anticoagulation clinic. PMID- 27657122 TI - Impact of the Content of Fatty Acids of Oral Fat Tolerance Tests on Postprandial Triglyceridemia: Systematic Review and Meta-Analysis. AB - : Whether the content of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) could differently influence postprandial triglycerides (TG) is unknown. We examined possible differences in the postprandial TG response to fat tolerance tests (FTTs), in which SFA or unsaturated fatty acids were used. Crossover clinical trials investigating the effects of FTTs containing SFA and unsaturated fats on postprandial triglyceridemia in databases from 1994 until 2016 were searched. Of 356 studies, 338 were excluded and 18 were considered. TG net incremental areas under the curve were calculated using time-points or changes from baseline. Pooled effects of standardized mean differences and I2 test were used. RESULTS: In 12 studies, responses to SFA versus PUFA meals, and in 16 studies versus MUFA meals were compared. Over 4 hours, no differences between SFA and unsaturated fats were observed. Over 8 hours a lower response to PUFA (SMD -2.28; 95%CI -4.16, -0.41) and a trend to lower response to MUFA (SMD -0.89, 95%CI -1.82, 0.04) were detected. FTTs shorter than 8 hours may not be sufficient to differentiate postprandial TG after challenges with distinct fatty acids. Clinical significance of different postprandial TG responses on cardiovascular risk in the long-term deserves investigation. PMID- 27657123 TI - The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction. AB - Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-kappaB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-kappaB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-kappaB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells. PMID- 27657124 TI - The Effects of Early Post-Operative Soluble Dietary Fiber Enteral Nutrition for Colon Cancer. AB - We examined colon cancer patients who received soluble dietary fiber enteral nutrition (SDFEN) to evaluate the feasibility and potential benefit of early SDFEN compared to EN. Sixty patients who were confirmed as having colon cancer with histologically and accepted radical resection of colon cancer were randomized into an SDFEN group and an EN group. The postoperative complications, length of hospital stay (LOH), days for first fecal passage, and the difference in nutritional status, immune function and inflammatory reaction between pre operation and post-operation were all recorded. The statistical analyses were performed using the t-test and the chi square test. Statistical significance was defined as p < 0.05. After the nutrition support, differences in the levels of albumin, prealbumin and transferrin in each group were not statistically significant (p > 0.05); the levels of CD4+, IgA and IgM in the SDFEN group were higher than that of the EN group at seven days (p < 0.05); the levels of TNF alpha and IL-6 in the SDFEN group were lower than that of the EN group at seven days (p < 0.05); and patients in the SDFEN group had a significantly shorter first flatus time than the EN group (p < 0.05). Early post-operative SDFEN used in colon cancer patients was feasible and beneficial in immune function and reducing inflammatory reaction, gastrointestinal function and speeding up the recovery. PMID- 27657125 TI - Total and Free Sugar Content of Canadian Prepackaged Foods and Beverages. AB - A number of recommendations for policy and program interventions to limit excess free sugar consumption have emerged, however there are a lack of data describing the amounts and types of sugar in foods. This study presents an assessment of sugar in Canadian prepackaged foods including: (a) the first systematic calculation of free sugar contents; (b) a comprehensive assessment of total sugar and free sugar levels; and (c) sweetener and free sugar ingredient use, using the University of Toronto's Food Label Information Program (FLIP) database 2013 (n = 15,342). Food groups with the highest proportion of foods containing free sugar ingredients also had the highest median total sugar and free sugar contents (per 100 g/mL): desserts (94%, 15 g, and 12 g), sugars and sweets (91%, 50 g, and 50 g), and bakery products (83%, 16 g, and 14 g, proportion with free sugar ingredients, median total sugar and free sugar content in Canadian foods, respectively). Free sugar accounted for 64% of total sugar content. Eight of 17 food groups had >=75% of the total sugar derived from free sugar. Free sugar contributed 20% of calories overall in prepackaged foods and beverages, with the highest at 70% in beverages. These data can be used to inform interventions aimed at limiting free sugar consumption. PMID- 27657127 TI - Exercise, Appetite and Weight Control: Are There Differences between Men and Women? AB - Recent years have witnessed significant research interest surrounding the interaction among exercise, appetite and energy balance, which has important implications for health. The majority of exercise and appetite regulation studies have been conducted in males. Consequently, opportunities to examine sex-based differences have been limited, but represent an interesting avenue of inquiry considering postulations that men experience greater weight loss after exercise interventions than women. This article reviews the scientific literature relating to the acute and chronic effects of exercise on appetite control in men and women. The consensus of evidence demonstrates that appetite, appetite-regulatory hormone and energy intake responses to acute exercise do not differ between the sexes, and there is little evidence indicating compensatory changes occur after acute exercise in either sex. Limited evidence suggests women respond to the initiation of exercise training with more robust compensatory alterations in appetite-regulatory hormones than men, but whether this translates to long-term differences is unknown. Current exercise training investigations do not support sex-based differences in appetite or objectively assessed energy intake, and increasing exercise energy expenditure elicits at most a partial energy intake compensation in both sexes. Future well-controlled acute and chronic exercise studies directly comparing men and women are required to expand this evidence base. PMID- 27657128 TI - Healthy Dietary Patterns and Oxidative Stress as Measured by Fluorescent Oxidation Products in Nurses' Health Study. AB - Healthy diets may lower oxidative stress and risk of chronic diseases. However, no previous studies examined associations between diet and fluorescent oxidation products (FlOP), a global marker of oxidative stress. We evaluated associations between healthy eating patterns (Alternative Healthy Eating Index (AHEI), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (aMED)) and FlOP, measured at three excitation/emission wavelengths (FlOP_360, FlOP_320, FlOP_400) from 2021 blood samples collected from 1688 women within the Nurses' Health Study. AHEI, DASH, and aMED scores were significantly positively associated with FlOP_360 and FlOP_320 concentrations (p-trend <= 0.04), but not associated with FlOP_400. Among specific food groups that contribute to these diet scores, significantly positive associations were observed with legumes and vegetables for FlOP_360, vegetables and fruits for FlOP_320, and legumes and alcohol for FlOP_400. Inverse associations were observed with nuts, sweets or desserts, and olive oil for FlOP_360, nuts for FlOP_320 and sweets or desserts for FlOP_400 (all p-trend <= 0.05). However, FlOP variation due to diet was small compared to overall FlOP variation. In conclusion, AHEI, DASH, and aMED scores were unexpectedly positively, but weakly, associated with FlOP_360 and FlOP_320. However, these findings should be interpreted cautiously as the determinants of FlOP concentrations are not fully understood. PMID- 27657130 TI - Erratum: Lazar-Karsten, P., et al. Generation and Characterization of Vascular Smooth Muscle Cell Lines Derived from a Patient with a Bicuspid Aortic Valve. Cells 2016, 5, 19. AB - The authors wish to make the following erratum to this paper [1].[...]. PMID- 27657129 TI - Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy. AB - A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer. PMID- 27657131 TI - Eight Mutations of Three Genes (EDA, EDAR, and WNT10A) Identified in Seven Hypohidrotic Ectodermal Dysplasia Patients. AB - Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the teeth, hair, and sweat glands. Ectodysplasin A (EDA), Ectodysplasin A receptor (EDAR), and EDAR-associated death domain (EDARADD) are candidate genes for HED, but the relationship between WNT10A and HED has not yet been validated. In this study, we included patients who presented at least two of the three ectodermal dysplasia features. The four genes were analyzed in seven HED patients by PCR and Sanger sequencing. Five EDA and one EDAR heterozygous mutations were identified in families 1-6. Two WNT10A heterozygous mutations were identified in family 7 as a compound heterozygote. c.662G>A (p.Gly221Asp) in EDA and c.354T>G (p.Tyr118*) in WNT10A are novel mutations. Bioinformatics analyses results confirmed the pathogenicity of the two novel mutations. In family 7, we also identified two single-nucleotide polymorphisms (SNPs) that were predicted to affect the splicing of EDAR. Analysis of the patient's total RNA revealed normal splicing of EDAR. This ascertained that the compound heterozygous WNT10A mutations are the genetic defects that led to the onset of HED. Our data revealed the genetic basis of seven HED patients and expended the mutational spectrum. Interestingly, we confirmed WNT10A as a candidate gene of HED and we propose WNT10A to be tested in EDA-negative HED patients. PMID- 27657133 TI - Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia. AB - Mosaicism for FMR1 premutation (PM: 55-199 CGG)/full mutation (FM: >200 CGG) alleles or the presence of unmethylated FM (UFM) have been associated with a less severe fragile X syndrome (FXS) phenotype and fragile X associated tremor/ataxia syndrome (FXTAS)-a late onset neurodegenerative disorder. We describe a 38 year old male carrying a 100% methylated FM detected with Southern blot (SB), which is consistent with complete silencing of FMR1 and a diagnosis of fragile X syndrome. However, his formal cognitive scores were not at the most severe end of the FXS phenotype and he displayed tremor and ataxic gait. With the association of UFM with FXTAS, we speculated that his ataxia might be related to an undetected proportion of UFM alleles. Such UFM alleles were confirmed by more sensitive PCR based methylation testing showing FM methylation between 60% and 70% in blood, buccal, and saliva samples and real-time PCR analysis showing incomplete silencing of FMR1. While he did not meet diagnostic criteria for FXTAS based on MRI findings, the underlying cause of his ataxia may be related to UFM alleles not detected by SB, and follow-up clinical and molecular assessment are justified if his symptoms worsen. PMID- 27657134 TI - DNA Polymerase theta: A Unique Multifunctional End-Joining Machine. AB - The gene encoding DNA polymerase theta (Poltheta) was discovered over ten years ago as having a role in suppressing genome instability in mammalian cells. Studies have now clearly documented an essential function for this unique A family polymerase in the double-strand break (DSB) repair pathway alternative end joining (alt-EJ), also known as microhomology-mediated end-joining (MMEJ), in metazoans. Biochemical and cellular studies show that Poltheta exhibits a unique ability to perform alt-EJ and during this process the polymerase generates insertion mutations due to its robust terminal transferase activity which involves template-dependent and independent modes of DNA synthesis. Intriguingly, the POLQ gene also encodes for a conserved superfamily 2 Hel308-type ATP dependent helicase domain which likely assists in alt-EJ and was reported to suppress homologous recombination (HR) via its anti-recombinase activity. Here, we review our current knowledge of Poltheta-mediated end-joining, the specific activities of the polymerase and helicase domains, and put into perspective how this multifunctional enzyme promotes alt-EJ repair of DSBs formed during S and G2 cell cycle phases. PMID- 27657135 TI - Ups and Downs: Mechanisms of Repeat Instability in the Fragile X-Related Disorders. AB - The Fragile X-related disorders (FXDs) are a group of clinical conditions resulting from the expansion of a CGG/CCG-repeat tract in exon 1 of the Fragile X mental retardation 1 (FMR1) gene. While expansions of the repeat tract predominate, contractions are also seen with the net result being that individuals can show extensive repeat length heterogeneity in different tissues. The mechanisms responsible for expansion and contraction are still not well understood. This review will discuss what is known about these processes and current evidence that supports a model in which expansion arises from the interaction of components of the base excision repair, mismatch repair and transcription coupled repair pathways. PMID- 27657137 TI - Implementing Personalized Medicine in the Academic Health Center. AB - Recently we at Partners Health Care had a series of articles in the Journal of Personalized Medicine describing how we are going about implementing Personalized Medicine in an academic health care system [1-10].[...]. PMID- 27657132 TI - The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype. AB - Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype). PMID- 27657126 TI - The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms. AB - The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs) via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer. PMID- 27657136 TI - Regulation of BLM Nucleolar Localization. AB - Defects in coordinated ribosomal RNA (rRNA) transcription in the nucleolus cause cellular and organismal growth deficiencies. Bloom's syndrome, an autosomal recessive human disorder caused by mutated recQ-like helicase BLM, presents with growth defects suggestive of underlying defects in rRNA transcription. Our previous studies showed that BLM facilitates rRNA transcription and interacts with RNA polymerase I and topoisomerase I (TOP1) in the nucleolus. The mechanisms regulating localization of BLM to the nucleolus are unknown. In this study, we identify the TOP1-interaction region of BLM by co-immunoprecipitation of in vitro transcribed and translated BLM segments and show that this region includes the highly conserved nuclear localization sequence (NLS) of BLM. Biochemical and nucleolar co-localization studies using site-specific mutants show that two serines within the NLS (S1342 and S1345) are critical for nucleolar localization of BLM but do not affect the functional interaction of BLM with TOP1. Mutagenesis of both serines to aspartic acid (phospho-mimetic), but not alanine (phospho dead), results in approximately 80% reduction in nucleolar localization of BLM while retaining the biochemical functions and nuclear localization of BLM. Our studies suggest a role for this region in regulating nucleolar localization of BLM via modification of the two serines within the NLS. PMID- 27657138 TI - Gene Disruption Technologies Have the Potential to Transform Stored Product Insect Pest Control. AB - Stored product insects feed on grains and processed commodities manufactured from grain post-harvest, reducing the nutritional value and contaminating food. Currently, the main defense against stored product insect pests is the pesticide fumigant phosphine. Phosphine is highly toxic to all animals, but is the most effective and economical control method, and thus is used extensively worldwide. However, many insect populations have become resistant to phosphine, in some cases to very high levels. New, environmentally benign and more effective control strategies are needed for stored product pests. RNA interference (RNAi) may overcome pesticide resistance by targeting the expression of genes that contribute to resistance in insects. Most data on RNAi in stored product insects is from the coleopteran genetic model, Tribolium castaneum, since it has a strong RNAi response via injection of double stranded RNA (dsRNA) in any life stage. Additionally, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has been suggested as a potential resource for new pest control strategies. In this review we discuss background information on both gene disruption technologies and summarize the advances made in terms of molecular pest management in stored product insects, mainly T. castaneum, as well as complications and future needs. PMID- 27657139 TI - Vegetarian versus Meat-Based Diets for Companion Animals. AB - Companion animal owners are increasingly concerned about the links between degenerative health conditions, farm animal welfare problems, environmental degradation, fertilizers and herbicides, climate change, and causative factors; such as animal farming and the consumption of animal products. Accordingly, many owners are increasingly interested in vegetarian diets for themselves and their companion animals. However, are vegetarian canine and feline diets nutritious and safe? Four studies assessing the nutritional soundness of these diets were reviewed, and manufacturer responses to the most recent studies are provided. Additional reviewed studies examined the nutritional soundness of commercial meat based diets and the health status of cats and dogs maintained on vegetarian and meat-based diets. Problems with all of these dietary choices have been documented, including nutritional inadequacies and health problems. However, a significant and growing body of population studies and case reports have indicated that cats and dogs maintained on vegetarian diets may be healthy including those exercising at the highest levels-and, indeed, may experience a range of health benefits. Such diets must be nutritionally complete and reasonably balanced, however, and owners should regularly monitor urinary acidity and should correct urinary alkalinisation through appropriate dietary additives, if necessary. PMID- 27657140 TI - Changes in the Welfare of an Injured Working Farm Dog Assessed Using the Five Domains Model. AB - The present structured, systematic and comprehensive welfare evaluation of an injured working farm dog using the Five Domains Model is of interest in its own right. It is also an example for others wanting to apply the Model to welfare evaluations in different species and contexts. Six stages of a fictitious scenario involving the dog are considered: (1) its on-farm circumstances before one hind leg is injured; (2) its entanglement in barbed wire, cutting it free and transporting it to a veterinary clinic; (3) the initial veterinary examination and overnight stay; (4) amputation of the limb and immediate post-operative recovery; (5) its first four weeks after rehoming to a lifestyle block; and (6) its subsequent life as an amputee and pet. Not all features of the scenario represent average-to-good practice; indeed, some have been selected to indicate poor practice. It is shown how the Model can draw attention to areas of animal welfare concern and, importantly, to how welfare enhancement may be impeded or facilitated. Also illustrated is how the welfare implications of a sequence of events can be traced and evaluated, and, in relation to specific situations, how the degrees of welfare compromise and enhancement may be graded. In addition, the choice of a companion animal, contrasting its welfare status as a working dog and pet, and considering its treatment in a veterinary clinical setting, help to highlight various welfare impacts of some practices. By focussing attention on welfare problems, the Model can guide the implementation of remedies, including ways of promoting positive welfare states. Finally, wider applications of the Five Domains Model are noted: by enabling both negative and positive welfare relevant experiences to be graded, the Model can be applied to quality of life assessments and end-of-life decisions and, with particular regard to negative experiences, the Model can also help to strengthen expert witness testimony during prosecutions for serious ill treatment of animals. PMID- 27657141 TI - Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories. AB - Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray pp. PMID- 27657142 TI - A Review of Antioxidant Peptides Derived from Meat Muscle and By-Products. AB - Antioxidant peptides are gradually being accepted as food ingredients, supplemented in functional food and nutraceuticals, to positively regulate oxidative stress in the human body against lipid and protein oxidation. Meat muscle and meat by-products are rich sources of proteins and can be regarded as good materials for the production of bioactive peptides by use of enzymatic hydrolysis or direct solvent extraction. In recent years, there has been a growing number of studies conducted to characterize antioxidant peptides or hydrolysates derived from meat muscle and by-products as well as processed meat products, including dry-cured hams. Antioxidant peptides obtained from animal sources could exert not only nutritional value but also bioavailability to benefit human health. This paper reviews the antioxidant peptides or protein hydrolysates identified in muscle protein and by-products. We focus on the procedure for the generation of peptides with antioxidant capacity including the acquisition of crude peptides, the assessment of antioxidant activity, and the purification and identification of the active fraction. It remains critical to perform validation experiments with a cell model, animal model or clinical trial to eliminate safety concerns before final application in the food system. In addition, some of the common characteristics on structure-activity relationship are also reviewed based on the identified antioxidant peptides. PMID- 27657143 TI - Integration of Methane Steam Reforming and Water Gas Shift Reaction in a Pd/Au/Pd Based Catalytic Membrane Reactor for Process Intensification. AB - Palladium-based catalytic membrane reactors (CMRs) effectively remove H2 to induce higher conversions in methane steam reforming (MSR) and water-gas-shift reactions (WGS). Within such a context, this work evaluates the technical performance of a novel CMR, which utilizes two catalysts in series, rather than one. In the process system under consideration, the first catalyst, confined within the shell side of the reactor, reforms methane with water yielding H2, CO and CO2. After reforming is completed, a second catalyst, positioned in series, reacts with CO and water through the WGS reaction yielding pure H2O, CO2 and H2. A tubular composite asymmetric Pd/Au/Pd membrane is situated throughout the reactor to continuously remove the produced H2 and induce higher methane and CO conversions while yielding ultrapure H2 and compressed CO2 ready for dehydration. Experimental results involving (i) a conventional packed bed reactor packed (PBR) for MSR, (ii) a PBR with five layers of two catalysts in series and (iii) a CMR with two layers of two catalysts in series are comparatively assessed and thoroughly characterized. Furthermore, a comprehensive 2D computational fluid dynamics (CFD) model was developed to explore further the features of the proposed configuration. The reaction was studied at different process intensification-relevant conditions, such as space velocities, temperatures, pressures and initial feed gas composition. Finally, it is demonstrated that the above CMR module, which was operated for 600 h, displays quite high H2 permeance and purity, high CH4 conversion levels and reduced CO yields. PMID- 27657146 TI - Potential of Surface Enhanced Raman Spectroscopy (SERS) in Therapeutic Drug Monitoring (TDM). A Critical Review. AB - Surface-Enhanced Raman Spectroscopy (SERS) is a label-free technique that enables quick monitoring of substances at low concentrations in biological matrices. These advantages make it an attractive tool for the development of point-of-care tests suitable for Therapeutic Drug Monitoring (TDM) of drugs with a narrow therapeutic window, such as chemotherapeutic drugs, immunosuppressants, and various anticonvulsants. In this article, the current applications of SERS in the field of TDM for cancer therapy are discussed in detail and illustrated according to the different strategies and substrates. In particular, future perspectives are provided and special concerns regarding the standardization of self-assembly methods and nanofabrication procedures, quality assurance, and technology readiness are critically evaluated. PMID- 27657147 TI - Lactate Sensors on Flexible Substrates. AB - Lactate detection by an in situ sensor is of great need in clinical medicine, food processing, and athletic performance monitoring. In this paper, a flexible, easy to fabricate, and low-cost biosensor base on lactate oxidase is presented. The fabrication processes, including metal deposition, sol-gel IrOx deposition, and drop-dry enzyme loading method, are described in detail. The loaded enzyme was examined by scanning electron microscopy. Cyclic voltammetry was used to characterize the sensors. Durability, sensibility, and selectivity of the biosensors were examined. The comparison for different electrode sizes and different sensing film materials was conducted. The sensor could last for four weeks with an average surface area normalized sensitivity of 950 nA/(cm2 mM) and 9250 nA/(cm2 mM) for Au-based electrodes, and IrOx-modified electrodes respectively, both with an electrode size of 100 * 50 MUm. The self-referencing method to record noises simultaneously with the working electrode greatly improved sensor sensitivity and selectivity. The sensor showed little response to interference chemicals, such as glutamate and dopamine. PMID- 27657144 TI - Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery. AB - Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID- 27657148 TI - Untargeted NMR Spectroscopic Analysis of the Metabolic Variety of New Apple Cultivars. AB - Metabolome analyses by NMR spectroscopy can be used in quality control by generating unique fingerprints of different species. Hundreds of components and their variation between different samples can be analyzed in a few minutes/hours with high accuracy and low cost of sample preparation. Here, apple peel and pulp extracts of a variety of apple cultivars were studied to assess their suitability to discriminate between the different varieties. The cultivars comprised mainly newly bred varieties or ones that were brought onto the market in recent years. Multivariate analyses of peel and pulp extracts were able to unambiguously identify all cultivars, with peel extracts showing a higher discriminative power. The latter was increased if the highly concentrated sugar metabolites were omitted from the analysis. Whereas sugar concentrations lay within a narrow range, polyphenols, discussed as potential health promoting substances, and acids varied remarkably between the cultivars. PMID- 27657145 TI - Advances in the Microbiome: Applications to Clostridium difficile Infection. AB - Clostridium difficile is a major cause of morbidity and mortality worldwide, causing over 400,000 infections and approximately 29,000 deaths in the United States alone each year. C. difficile is the most common cause of nosocomial diarrhoea in the developed world, and, in recent years, the emergence of hyper virulent (mainly ribotypes 027 and 078, sometimes characterised by increased toxin production), epidemic strains and an increase in the number of community acquired infections has caused further concern. Antibiotic therapy with metronidazole, vancomycin or fidaxomicin is the primary treatment for C. difficile infection (CDI). However, CDI is unique, in that, antibiotic use is also a major risk factor for acquiring CDI or recurrent CDI due to disruption of the normal gut microbiota. Therefore, there is an urgent need for alternative, non-antibiotic therapeutics to treat or prevent CDI. Here, we review a number of such potential treatments which have emerged from advances in the field of microbiome research. PMID- 27657149 TI - Associations between Trunk Extension Endurance and Isolated Lumbar Extension Strength in Both Asymptomatic Participants and Those with Chronic Low Back Pain. AB - BACKGROUND: Strength and endurance tests are important for both clinical practice and research due to the key role they play in musculoskeletal function. In particular, deconditioning of the lumbar extensor musculature has been associated with low back pain (LBP). Due to the relationship between strength and absolute endurance, it is possible that trunk extension (TEX) endurance tests could provide a proxy measure of isolated lumbar extension (ILEX) strength and thus represent a simple, practical alternative to ILEX measurements. Though, the comparability of TEX endurance and ILEX strength is presently unclear and so the aim of the present study was to examine this relationship. METHODS: Thirty eight healthy participants and nineteen participants with non-specific chronic LBP and no previous lumbar surgery participated in this cross-sectional study design. TEX endurance was measured using the Biering-Sorensen test. A maximal ILEX strength test was performed on the MedX lumbar-extension machine. RESULTS: A Pearson's correlation revealed no relationship between TEX endurance and ILEX strength in the combined group (r = 0.035, p = 0.793), the chronic LBP group (r = 0.120, p = 0.623) or the asymptomatic group (r = -0.060, p = 0.720). CONCLUSIONS: The results suggest that TEX is not a good indicator of ILEX and cannot be used to infer results regarding ILEX strength. However, a combination of TEX and ILEX interpreted together likely offers the greatest and most comprehensive information regarding lumbo-pelvic function during extension. PMID- 27657151 TI - Parental Protectiveness Mediates the Association between Parent-Perceived Child Self-Efficacy and Health Outcomes in Pediatric Functional Abdominal Pain Disorder. AB - Previous studies have shown that parental protectiveness is associated with increased pain and disability in Functional Abdominal Pain Disorder (FAPD) but the role that perceived child self-efficacy may play remains unclear. One reason why parents may react protectively towards their child's pain is that they perceive their child to be unable to cope or function normally while in pain (perceived low self-efficacy). This study sought to examine (a) the association between parent-perceived child pain self-efficacy and child health outcomes (symptom severity and disability); and (b) the role of parental protectiveness as a mediator of this association. Participants were 316 parents of children aged 7 12 years with FAPD. Parents completed measures of perceived child self-efficacy when in pain, their own protective responses to their child's pain, child gastrointestinal (GI) symptom severity, and child functional disability. Parent perceived child self-efficacy was inversely associated with parent-reported child GI symptom severity and disability, and parental protectiveness mediated these associations. These results suggest that parents who perceive their child to have low self-efficacy to cope with pain respond more protectively when they believe he/she is in pain, and this, in turn, is associated with higher levels of GI symptoms and disability in their child. This finding suggests that directly addressing parent beliefs about their child's ability to manage pain should be included as a component of FAPD, and potentially other child treatment interventions. PMID- 27657150 TI - Comparison of Very Low Energy Diet Products Available in Australia and How to Tailor Them to Optimise Protein Content for Younger and Older Adult Men and Women. AB - Very low energy diets (VLED) are efficacious in inducing rapid weight loss but may not contain adequate macronutrients or micronutrients for individuals with varying nutritional requirements. Adequate protein intake during weight loss appears particularly important to help preserve fat free mass and control appetite, and low energy and carbohydrate content also contributes to appetite control. Therefore, the purpose of this study was to compare the nutritional content (with a focus on protein), nutritional adequacy and cost of all commercially-available VLED brands in Australia. Nutritional content and cost were extracted and compared between brands and to the Recommended Dietary Intake (RDI) or adequate intake (AI) of macronutrients and micronutrients for men and women aged 19-70 years or >70 years. There was wide variability in the nutritional content, nutritional adequacy and cost of VLED brands. Most notably, even brands with the highest daily protein content, based on consuming three products/day (KicStartTM and Optislim((r)), ~60 g/day), only met estimated protein requirements of the smallest and youngest women for whom a VLED would be indicated. Considering multiple options to optimise protein content, we propose that adding pure powdered protein is the most suitable option because it minimizes additional energy, carbohydrate and cost of VLEDs. PMID- 27657153 TI - Access to joint replacement: have we got it right? PMID- 27657152 TI - Rewiring of Developing Spinal Nociceptive Circuits by Neonatal Injury and Its Implications for Pediatric Chronic Pain. AB - Significant evidence now suggests that neonatal tissue damage can evoke long lasting changes in pain sensitivity, but the underlying cellular and molecular mechanisms remain unclear. This review highlights recent advances in our understanding of how injuries during a critical period of early life modulate the functional organization of synaptic networks in the superficial dorsal horn (SDH) of the spinal cord in a manner that favors the excessive amplification of ascending nociceptive signaling to the brain, which likely contributes to the generation and/or maintenance of pediatric chronic pain. These persistent alterations in synaptic function within the SDH may also contribute to the well documented "priming" of developing pain pathways by neonatal tissue injury. PMID- 27657155 TI - Access to orthopaedic spinal specialists in the Canterbury public health system: quantifying the unmet need. AB - AIM: The aim of this project was to determine the unmet need within the public health system for patients referred for elective Orthopaedic Specialist Spinal assessment and treatment in the Canterbury District Health Board (CDHB) region. METHODS: Between January 2014 and January 2015 data was collected from all elective referrals to the CDHB Orthopaedic Spinal Service. During this period, the number of available outpatient appointments was set by the CDHB. Within this clinical capacity, patients were triaged by the four consultant surgeons into those of most need based on the referral letter and available radiological imaging. Those unable to be provided with a clinical appointment were discharged back to their GP for ongoing conservative care. Of those patients that received specialist assessment and were considered in need of elective surgical intervention, a proportion were denied treatment if the surgery was unable to be performed within the government determined four-month waiting time threshold. RESULTS: During the study period, 707 patients were referred to the CDHB orthopaedic spinal team for elective specialist assessment. Of these, 522 (74%) were declined an outpatient appointment due to a lack of available clinical time. Of the 185 patients given a specialist assessment, 158 (85%) were recommended for elective surgery. Ninety-one (58%) were denied surgery and referred back for ongoing GP care due to unavailable operating capacity within the four-month waiting list threshold. Within this group of 91 patients, 16 patients were declined on multiple occasions (14 patients twice and two patients on three occasions). CONCLUSIONS: This study quantifies the unmet need for both Spinal Orthopaedic Specialist assessment and, if warranted, surgical management of elective spine conditions within the Canterbury public health system. It highlights the degree of rationing within the public health system and its failure to adequately provide for the Canterbury Public. PMID- 27657154 TI - Equity of publicly-funded hip and knee joint replacement surgery in New Zealand: results from a national observational study. AB - AIM: This study examines equity in the provision of publicly-funded hip and knee total joint replacement (TJR) surgery in New Zealand between 2006 and 2013 to: 1) investigate national rates by demographic characteristics; 2) describe changes in national rates over time; and 3) compare rates of provision between District Health Boards (DHBs). METHODS: Hospital discharge data for people aged 20 years or over who had at least one hip or knee TJR between 2006 and 2013 was obtained from the Ministry of Health's National Minimum Dataset. RESULTS: Higher TJR rates were observed among those aged 75-84 years, females, those of Maori ethnicity, those not living in rural or main urban areas and those in the most deprived socio-economic groups. TJRs increased from 7,053 in 2006 to 8,429 in 2013, however the rate was highest in 2007. In 2012-13, age-ethnicity-standardised rates varied between DHBs from 196 to 419/100,000 person years, with larger DHBs having lower rates than smaller DHBs. CONCLUSION: There was evidence of geographic inequity in TJR provision across New Zealand. Despite increased numbers of procedures, rates of publicly-funded TJR surgery are barely keeping up with population increases. Reasons behind differences in provision should be examined. PMID- 27657156 TI - Rebalancing health service use for older people: simulating policy-relevant scenarios under demographic ageing. AB - AIMS: The demographic ageing of New Zealand society has greatly increased the proportion of older people (aged 65 years and over), with major policy implications. We tested the effects on health service use of alterations to morbidity profile and the balance of care. METHODS: We developed a microsimulation model using data from an official national health survey series to generate a synthetic replicate for scenario testing. RESULTS: Projections on current settings from 2001 to 2021 showed increases in morbidity-long-term illness (2%)-and in health service use-doctor visits (21%), public hospital admissions (16%). Scenarios with decreasing morbidity levels showed moderate reductions in health service use. By contrast, rebalancing towards the use of practice nurses showed a large decrease in public hospital admissions for people aged 85 years and over. CONCLUSION: Demographic ageing may not have a major negative effect on system resources in New Zealand and other developed countries. Rebalancing between modalities of care may soften the impact of increasing health service use required by a larger older population. PMID- 27657157 TI - Epidemiology of intussusception in New Zealand pre-rotavirus vaccination. AB - AIMS: To describe the epidemiology of intussusception in New Zealand children aged 0-36 months prior to the introduction of routine rotavirus vaccination. METHODS: ICD-10 coding data from the New Zealand National Minimum Data Set (NMDS) was used to identify all cases of intussusception in children aged 0-36 months between January 1998 and December 2013. These data were linked with birth data from the New Zealand census. Population incidence rates of intussusception were calculated, and demographic characteristics described. RESULTS: Over the 16-year study period, there were 794 cases of intussusception. The majority (56%) occurred in the first year of life (age adjusted incidence rate 56.1/100,000 child-years, 95% confidence interval (CI) 41.7-71.2). Intussusception occurred more frequently in males (36.4/100,000 (95% CI 24.6-48.2) versus 19.5/100,000 (95% CI 10.8-28.1, p<0.001)). There was no difference in intussusception incidence between ethnic groups, although cases occurred at a younger age in Maori and Pacific infants compared to Asian and other ethnicities (Pacific median 7.5 months (interquartile range 5.9-11.6), Maori 7.8 months (IQR 5.5-12.3), European 9.2 months (IQR 5.8-15.8), Other Ethnicity 10.2 months (IQR 8.2-12.3), Asian 10.5 months (IQR 7.0-17.1 )). There was a weak seasonal trend with incidence troughs in January and July, and corresponding peaks in March and September. There was wide variation in presentation rates across District Health Board (DHB) regions, with a national average of 18.0/100,000 child-years (95% CI 9.7-26.3). Most patients were admitted on a single occasion to a single hospital for treatment (81%). CONCLUSIONS: This study updates background incidence rates of intussusception prior to the introduction of a national rotavirus vaccination programme in July 2014. It identifies a trend of earlier intussusception in Maori and Pacific infants; the relationship between earlier intussusception and the risk of vaccine-associated events is unknown. PMID- 27657158 TI - Publication rates and characteristics of undergraduate medical theses in New Zealand. AB - AIM: Publication in peer-reviewed journals is widely regarded as the preferred vehicle for research dissemination. In New Zealand, the fate and publication rates of theses produced by medical students is unknown. The aim of this study was to examine the frequency and characteristics of publications derived from research conducted by Bachelor of Medical Sciences (BMedSc(Hons)) students at the three campuses of the University of Otago Medical School, New Zealand. METHODS: A total of 153 BMedSc(Hons) theses accepted at the Otago Medical School during the period of January 1995 to December 2014 were analysed. Using standardised search criteria, PubMed and Google Scholar databases were searched in October 2015 to examine the number and characteristics of publications. RESULTS: Overall, 50 (32.7%) out of 153 included theses resulted in 81 scientific publications. Ten (12.3%) publications featured in Australasian journals. The majority of publications were original articles (84%), with pathology and molecular biology (19%) being the most common research area. Although they did not reach statistical significance, publications in higher impact factor journals trended towards having a senior first author as opposed to a student first author (p=0.06). CONCLUSION: Although higher than reported figures from previous studies, publication rates of BMedSc(Hons) theses remain lower than expected. To improve our understanding of medical student publishing in New Zealand, formal examination of the factors hindering medical students from publishing their theses is imperative. PMID- 27657159 TI - How effective is our current Orthopaedic Prioritisation Tool for scoring patients for arthroplasty surgery? AB - AIM: To compare those patients who are being accepted onto the waiting list for total hip and knee arthroplasty surgery with those patients who are being declined surgery, using a validated functional questionnaire. METHOD: The clinic records from all patients seen for consideration of total hip or knee arthroplasty at Hawkes Bay Hospital during the preceding four months were reviewed. We sent the Oxford Hip and Knee Score questionnaire to all patients who had been put forward for consideration of surgery. RESULTS: Of the 150 patients we surveyed, 81 had been accepted onto the waiting list and received a date for surgery within the next four months and 69 had been declined surgery. Of the 81 patients who had been accepted onto the waiting list for surgery, 61 returned the Oxford questionnaire with an average score of 10.9. Of the 69 patients who had been declined surgery, 59 returned the Oxford questionnaire with an average score of 10.8. Thus the mean Oxford score was not statistically different between those patients being accepted onto the waiting list for surgery and those being declined surgery (p=0.925). CONCLUSION: No difference was found between those patients being accepted onto the waiting list for total hip or knee arthroplasty and those being declined surgery in Hawkes Bay after using the Oxford Hip and Knee Score as a measure of functional impairment. The average Oxford score indicates that patients being seen in Hawkes Bay Hospital for consideration of total hip or knee arthroplasty are severely functionally impaired as a result of their condition. PMID- 27657160 TI - Parental smoking during pregnancy: findings from the Growing Up in New Zealand cohort. AB - AIMS: To investigate patterns of exposure to tobacco smoke in pregnancy among a representative sample of New Zealand women. METHODS: Analyses of smoking-related data from the first wave of the Growing Up in New Zealand cohort study, ie from the first data-collection point during the antenatal period in 2009-10. RESULTS: Twenty percent of mothers reporting smoking before pregnancy and 9.9% of mothers continued during pregnancy. These figures were higher in younger women (p<.0001), women with lower educational achievement (p<.001) and Maori women (p<.001). Similarly, being Maori (p<.0001) and having a lower education achievement (p<.0029) were associated with smoking during an unplanned compared to a planned pregnancy. Multiparous mothers were more likely to be smokers than primaparous mothers (11%: 95% Confidence Interval [CI] 10.0-12.1 vs 8.3%: 95% CI 7.2-9.4). Second-hand smoke exposure was more common for younger women (Odds Ratio [OR] 3.2: 95% CI 1.6-6.4), Maori women (OR 1.9: 95% CI 1.4-2.5), and women with unplanned pregnancies (OR 3.4 95% CI 12.0-14.8). CONCLUSIONS: There are differences in a range of contextual and behavioural factors related to smoking before and during pregnancy. Low educational achievement, being young, Maori and multiparous were all associated with smoking during pregnancy. A better understanding of why these differences exist is needed in order to find appropriate interventions to support women in becoming smoke-free. PMID- 27657161 TI - Low FODMAP diet efficacy in IBS patients-what is the evidence and what else do we need to know? AB - Irritable Bowel Syndrome (IBS) is a common and significant health problem which may be treatable with dietary interventions. Here we aim to explain the principles of the low Fermentable Oligo-, Di-, Monosaccharides and Polyol diet, and discuss both the limitations and opportunities of the diet in those with IBS, a common cause of presentation to primary and secondary care in New Zealand. PMID- 27657162 TI - Gingival lipoma. PMID- 27657163 TI - Rare coexistence of dermatomyositis and smooth muscle antibodies, with abnormal liver function tests. PMID- 27657164 TI - Exercise-induced rhabdomyolysis. AB - We report the case of a 34 year-old man who developed exercise-induced rhabdomyolysis after unaccustomed high-intensity exercise. Subclinical rhabdomyolysis is common after heavy exercise, yet it is uncommon for patients to seek medical advice. The presentation is variable and despite potentially life threatening complications the diagnosis may be easily missed by patients and healthcare professionals. A high-index of suspicion is critical to avoid missing the diagnosis. We summarise the current knowledge, clinical course, complications and management of exercise-induced rhabdomyolysis. PMID- 27657165 TI - Homeopathy-when self-regulation fails. PMID- 27657166 TI - Borderline personality pathology and physical health: The role of employment. AB - Borderline personality disorder (BPD) is associated with negative physical health outcomes. Clinical case studies suggest that employment status may buffer against the negative effects of BPD on physical health. The goal of the current study was to examine the interaction between BPD features and employment status in predicting subjective perceptions of physical health. We hypothesized that employment status would moderate the relationship between BPD features and physical health, such that individuals who are employed would exhibit a weaker negative relationship between BPD features and self- and informant ratings of physical health. We investigated this question using data from a community sample of 1,630 middle-aged to older adults participating in the St. Louis Personality and Aging Network, an ongoing study of personality, health, and aging. Results indicated that employment status and BPD features were significant predictors of both self- and informant ratings of physical health. Confirming our hypothesis, the interaction term contributed to a significant increase in the proportion of explained variance, suggesting that employment is associated with a weaker negative relationship between BPD features and physical health. These findings highlight the importance of examining occupational functioning in the long-term course of BPD and offer avenues for further research into moderators of the relationship between BPD features and physical health. (PsycINFO Database Record PMID- 27657169 TI - Tetherin is an exosomal tether. AB - Exosomes are extracellular vesicles that are released when endosomes fuse with the plasma membrane. They have been implicated in various functions in both health and disease, including intercellular communication, antigen presentation, prion transmission, and tumour cell metastasis. Here we show that inactivating the vacuolar ATPase in HeLa cells causes a dramatic increase in the production of exosomes, which display endocytosed tracers, cholesterol, and CD63. The exosomes remain clustered on the cell surface, similar to retroviruses, which are attached to the plasma membrane by tetherin. To determine whether tetherin also attaches exosomes, we knocked it out and found a 4-fold reduction in plasma membrane associated exosomes, with a concomitant increase in exosomes discharged into the medium. This phenotype could be rescued by wild-type tetherin but not tetherin lacking its GPI anchor. We propose that tetherin may play a key role in exosome fate, determining whether they participate in long-range or short-range interactions. PMID- 27657170 TI - Antimicrobial Properties of Tris(homoleptic) Ruthenium(II) 2-Pyridyl-1,2,3 triazole "Click" Complexes against Pathogenic Bacteria, Including Methicillin Resistant Staphylococcus aureus (MRSA). AB - A series of tris(homoleptic) ruthenium(II) complexes of 2-(1-R-1H-1,2,3-triazol-4 yl)pyridine "click" ligands (R-pytri) with various aliphatic (R = butyl, hexyl, octyl, dodecyl, and hexdecyl) and aromatic (R = phenyl and benzyl) substituents was synthesized in good yields (52%-66%). The [Ru(R-pytri)3]2+(X-)2 complexes (where X- = PF6- or Cl-) were characterized by elemental analysis, high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1H and 13C nuclear magnetic resonance (NMR) and infrared (IR) spectroscopies, and the molecular structures of six of the compounds confirmed by X-ray crystallography. 1H NMR analysis showed that the as-synthesized materials were a statistical mixture of the mer- and fac-[Ru(R-pytri)3]2+ complexes. These diastereomers were separated using column chromatography. The electronic structures of the mer- and fac-[Ru(R-pytri)3]2+ complexes were examined using ultraviolet-visible (UV-Vis) spectroscopy and cyclic and differential pulse voltammetry. The family of R-pytri ligands and the corresponding mer- and fac-[Ru(R-pytri)3]2+ complexes were tested for antimicrobial activity in vitro against both Staphylococcus aureus and Escherichia coli bacteria. Agar-based disk diffusion assays indicated that two of the [Ru(R-pytri)3](X)2 complexes (where X = PF6- and R = hexyl or octyl) displayed good antimicrobial activity against Gram-positive S. aureus and no activity against Gram-negative E. coli at the concentrations tested. The most active [Ru(R-pytri)3]2+ complexes ([Ru(hexpytri)3]2+ and Ru(octpytri)3]2+) were converted to the water-soluble chloride salts and screened for their activity against a wider range of pathogenic bacteria. As with the preliminary screen, the complexes showed good activity against a variety of Gram-positive strains (minimum inhibitory concentration (MIC) = 1-8 MUg/mL) but were less effective against Gram-negative bacteria (MIC = 16-128 MUg/mL). Most interestingly, in some cases, the ruthenium(II) "click" complexes proved more active (MIC = 4-8 MUg/mL) than the gentamicin control (MIC = 16 MUg/mL) against two strains of methicillin resistant S. aureus (MRSA) (MR 4393 and MR 4549). Transmission electron microscopy (TEM) experiments and propidium iodide assays suggested that the main mode of action for the ruthenium(II) R-pytri complexes was cell wall/cytoplasmic membrane disruption. Cytotoxicity experiments on human dermal keratinocyte and Vero (African green monkey kidney epithelial) cell lines suggested that the complexes were only modestly cytotoxic at concentrations well above the MIC values. PMID- 27657167 TI - Loss of ZBTB20 impairs circadian output and leads to unimodal behavioral rhythms. AB - Many animals display morning and evening bimodal activities in the day/night cycle. However, little is known regarding the potential components involved in the regulation of bimodal behavioral rhythms in mammals. Here, we identified that the zinc finger protein gene Zbtb20 plays a crucial role in the regulation of bimodal activities in mice. Depletion of Zbtb20 in nerve system resulted in the loss of early evening activity, but the increase of morning activity. We found that Zbtb20-deficient mice exhibited a pronounced decrease in the expression of Prokr2 and resembled phenotypes of Prok2 and Prokr2-knockout mice. Injection of adeno-associated virus-double-floxed Prokr2 in suprachiasmatic nucleus could partly restore evening activity in Nestin-Cre; Zbtb20fl/fl (NS-ZB20KO) mice. Furthermore, loss of Zbtb20 in Foxg1 loci, but intact in the suprachiasmatic nucleus, was not responsible for the unimodal activity of NS-ZB20KO mice. Our study provides evidence that ZBTB20-mediated PROKR2 signaling is critical for the evening behavioral rhythms. PMID- 27657171 TI - Catalytically Generated Allyl Cu(I) Intermediate via Cyclopropene Ring-Opening Coupling en Route to Allylphosphonates. AB - An efficient generation of functionalized allyl copper(I) species via cyclopropene ring-opening coupling reaction is reported, which enables stereoselective access to allylphosphonates. Mechanistic studies uncovered stereochemistry to be controlled by both ligand and substrate electronics, with the latter likely arising from pronounced arene-Cu(I) interaction in electron deficient substrates. The study unravels a novel approach to access functionalized nucleophilic allylcopper species upon which three-component coupling reactions might be developed. PMID- 27657168 TI - CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens. AB - Strong antibody response is considered a hallmark of a successful vaccine. While dendritic cells (DCs) are important for T follicular helper (Tfh) cell priming, how this process is regulated in vivo is unclear. We show here that the depletion of CD301b+ DCs specifically enhanced the development of Tfh cells, germinal center B cells and antibody responses against protein antigens. Exaggerated antibody responses in mice depleted of CD301b+ DCs occurred in the absence of any adjuvants, and resulting antibodies had broader specificity and higher affinity to the immunogen. CD301b+ DCs express high levels of PD-1 ligands, PD-L1 and PD L2. Blocking PD-1 or PD-L1 during priming in wild-type mice partially mimicked the phenotype of CD301b+ DC-depleted animals, suggesting their role in Tfh suppression. Transient depletion of CD301b+ DC results in the generation of autoreactive IgG responses. These results revealed a novel regulatory mechanism and a key role of CD301b+ DCs in blocking autoantibody generation. PMID- 27657172 TI - The Lower Terpenoids of Isocoma wrightii. PMID- 27657173 TI - How Negatively Charged Proteins Adsorb to Negatively Charged Surfaces: A Molecular Dynamics Study of BSA Adsorption on Silica. AB - How proteins adsorb to inorganic material surfaces is critically important for the development of new biotechnologies, since the orientation and structure of the adsorbed proteins impacts their functionality. While it is known that many negatively charged proteins readily adsorb to negatively charged oxide surfaces, a detailed understanding of how this process occurs is lacking. In this work we study the adsorption of BSA, an important transport protein that is negatively charged at physiological conditions, to a model silica surface that is also negatively charged. We use fully atomistic molecular dynamics to provide detailed understanding of the noncovalent interactions that bind the BSA to the silica surface. Our results provide new insight into the competing roles of long-range electrostatics and short-range forces, and the consequences this has for the orientation and structure of the adsorbed proteins. PMID- 27657174 TI - Room Temperature CO Oxidation over Pt/MgFe2O4: A Stable Inverse Spinel Oxide Support for Preparing Highly Efficient Pt Catalyst. AB - MgFe2O4 with inverse spinel structure is demonstrated to be an efficient support for constructing practical potential Pt catalyst (Pt/MgFe2O4). The resultant Pt/MgFe2O4 exhibits excellent catalytic behavior in CO oxidation under normal temperature and humidity. TOF calculated based on the content of Pt is 0.131 s-1. The excellent performance of Pt/MgFe2O4 attributes to the presence of surface undercoordinated lattice oxygens on MgFe2O4 support. These oxygens could participate in the initial CO oxidation and then be recovered under O2 conditions. Over this Pt/MgFe2O4 catalyst, CO catalytic oxidation should mainly follow a redox mechanism. PMID- 27657175 TI - Atomically Sharp Crack Tips in Monolayer MoS2 and Their Enhanced Toughness by Vacancy Defects. AB - We combine in situ transmission electron microscopy and large-scale molecular dynamics simulations to investigate brittle fracture in 2D monolayer MoS2, revealing that cracks propagate with a tip of atomic sharpness through the preferential direction with least energy release. We find that sparse vacancy defects cause crack deflections, while increasing defect density shifts the fracture mechanism from brittle to ductile by the migration of vacancies in the strain fields into networks. The fracture toughness of defective MoS2 is found to exceed that of graphene due to interactions between the atomically sharp crack tips and vacancy clusters during propagation. These results show that monolayer 2D materials are ideal for revealing fundamental aspects of fracture mechanics not previously possible with thicker materials, similar to studies of dislocation behavior in 2D materials. PMID- 27657176 TI - Atomic Migration Induced Crystal Structure Transformation and Core-Centered Phase Transition in Single Crystal Ge2Sb2Te5 Nanowires. AB - A phase change nanowire holds a promise for nonvolatile memory applications, but its transition mechanism has remained unclear due to the analytical difficulties at atomic resolution. Here we obtain a deeper understanding on the phase transition of a single crystalline Ge2Sb2Te5 nanowire (GST NW) using atomic scale imaging, diffraction, and chemical analysis. Our cross-sectional analysis has shown that the as-grown hexagonal close-packed structure of the single crystal GST NW transforms to a metastable face-centered cubic structure due to the atomic migration to the pre-existing vacancy layers in the hcp structure going through iterative electrical switching. We call this crystal structure transformation "metastabilization", which is also confirmed by the increase of set-resistance during the switching operation. For the set to reset transition between crystalline and amorphous phases, high-resolution imaging indicates that the longitudinal center of the nanowire mainly undergoes phase transition. According to the atomic scale analysis of the GST NW after repeated electrical switching, partial crystallites are distributed around the core-centered amorphous region of the nanowire where atomic migration is mainly induced, thus potentially leading to low power electrical switching. These results provide a novel understanding of phase change nanowires, and can be applied to enhance the design of nanowire phase change memory devices for improved electrical performance. PMID- 27657177 TI - New Generation Cadmium-Free Quantum Dots for Biophotonics and Nanomedicine. AB - This review summarizes recent progress in the design and applications of cadmium free quantum dots (Cd-free QDs), with an emphasis on their role in biophotonics and nanomedicine. We first present the features of Cd-free QDs and describe the physics and emergent optical properties of various types of Cd-free QDs whose applications are discussed in subsequent sections. Selected specific QD systems are introduced, followed by the preparation of these Cd-free QDs in a form useful for biological applications, including recent advances in achieving high photoluminescence quantum yield (PL QY) and tunability of emission color. Next, we summarize biophotonic applications of Cd-free QDs in optical imaging, photoacoustic imaging, sensing, optical tracking, and photothermal therapy. Research advances in the use of Cd-free QDs for nanomedicine applications are discussed, including drug/gene delivery, protein/peptide delivery, image-guided surgery, diagnostics, and medical devices. The review then considers the pharmacokinetics and biodistribution of Cd-free QDs and summarizes current studies on the in vitro and in vivo toxicity of Cd-free QDs. Finally, we provide perspectives on the overall current status, challenges, and future directions in this field. PMID- 27657179 TI - HIV Testing Experience Before HIV Diagnosis Among Men Who Have Sex with Men - 21 Jurisdictions, United States, 2007-2013. AB - Gay, bisexual, and other men who have sex with men (MSM) continue to be the population most affected by human immunodeficiency virus (HIV) in the United States. In 2014, 81% of diagnoses of HIV infection were among adult and adolescent males, and among these, 83% of infections were attributable to male-to male sexual contact (1). Since 2006, CDC has recommended HIV testing at least annually for sexually active MSM to foster early detection of HIV infection and prevent HIV transmission (2,3). Several initiatives and strategies during the past decade have aimed to expand HIV testing among MSM to increase early diagnosis and treatment and reduce transmission. To better understand HIV testing patterns among MSM with diagnosed HIV infection, CDC analyzed data for 2007-2013 from jurisdictions conducting HIV incidence surveillance as part of CDC's National HIV Surveillance System (NHSS). Findings from this analysis suggest that increasing percentages of MSM have had a negative HIV test during the 12 months before diagnosis (48% in 2007, 56% in 2013, among those with a known date of previous negative HIV test), indicating a trend toward increased HIV testing and earlier HIV diagnosis among persons most at risk for HIV. PMID- 27657178 TI - Discovery of Potent Antivirals against Amantadine-Resistant Influenza A Viruses by Targeting the M2-S31N Proton Channel. AB - Despite the existence of flu vaccines and small-molecule antiviral drugs, influenza virus infection remains a public health concern that warrants immediate attention. As resistance to the only orally bioavailable drug, oseltamivir, has been continuously reported, there is a clear need to develop the next-generation of anti-influenza drugs. We chose the influenza A virus M2-S31N mutant proton channel as the drug target to address this need as it is one of the most conserved viral proteins and persist in >95% of currently circulating influenza A viruses. In this study, we report the development of a late-stage diversification strategy for the expeditious synthesis of M2-S31N inhibitors. The channel blockage and antiviral activity of the synthesized compounds were tested in two electrode voltage clamp assays and antiviral assays, respectively. Several M2 S31N inhibitors were identified to have potent M2-S31N channel blockage and micromolar antiviral efficacy against several M2-S31N-containing influenza A viruses. PMID- 27657181 TI - Water-Promoted Regiospecific Azidolysis and Copper-Catalyzed Azide-Alkyne Cycloaddition: One-Pot Synthesis of 3-Hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H-1,2,3 triazol-1-yl)methyl]indolin-2-ones. AB - An efficient, eco-friendly, base free, one-pot, sequential protocol was developed for epoxide azidolysis and copper-catalyzed azide-alkyne cycloaddition using water as the solvent for the synthesis of 3-hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H 1,2,3-triazol-1-yl)methyl]indolin-2-ones. The optimized reaction conditions have been generalized in the case of aromatic as well as aliphatic alkyne partners to afford good yields and high regioselectivity. PMID- 27657182 TI - Gaps in health research in the Dominican Republic. AB - Objective To provide a basic profile of health research in the Dominican Republic by identifying health problems or diseases that have been addressed by studies implemented during the period 2009-2013 and to determine how well that research correlates with the burden of disease in the Dominican population. Methods This was a descriptive study that searched for primary and secondary data sources to identify health research implemented in the Dominican Republic in the years 2009 to 2013. Data about these projects were collected from the registries of clinicaltrials.gov and the Consejo Nacional de Bioetica en Salud, as well as from a questionnaire directed to researchers and managers. Disability-adjusted life years (DALYs) were derived from the Global Burden of Disease Study 2013 for males and females of all ages in the Dominican Republic and then compared with the number of research studies conducted on each specific health condition. Results This study identified 313 health research projects conducted in the Dominican Republic during the years 2009-2013. HIV/AIDS and lower respiratory infections were the two main topics researched; however, they accounted for a relatively small percentage of total DALYs in males and females of all ages in the Dominican Republic in 2013. Conclusions Limited research is directed toward addressing the health needs of Dominicans. The ongoing process of setting priorities for health research in the Dominican Republic should direct its efforts toward fixing this imbalance. PMID- 27657183 TI - Prevalence of chronic kidney disease of non-traditional causes in patients on hemodialysis in southwest Guatemala. AB - Objective To document the prevalence of patients on hemodialysis in southwestern Guatemala who have chronic kidney disease (CKD) of non-traditional causes (CKDnt). Methods This cross-sectional descriptive study interviewed patients on hemodialysis at the Instituto Guatemalteco de Seguridad Social on their health and occupational history. Laboratory serum, urine and vital sign data at the initiation of hemodialysis were obtained from chart reviews. Patients were classified according to whether they had hypertension or obesity or neither. The proportion of patients with and without these traditional CKD risk factors was recorded and the association between demographic and occupational factors and a lack of traditional CKD risk factors analyzed using multivariate logistic regression. Results Of 242 total patients (including 171 non-diabetics) enrolled in hemodialysis in southwestern Guatemala, 45 (18.6% of total patients and 26.3% of non-diabetics) lacked traditional CKD risk factors. While agricultural work history was common, only travel time greater than 30 minutes and age less than 50 years old were significantly associated with CKD in the absence of traditional risk factors. Individuals without such risk factors lived throughout southwestern Guatemala's five departments. Conclusions The prevalence of CKDnT appears to be much lower in this sample of patients receiving hemodialysis in Southwestern Guatemala than in hospitalized patients in El Salvador. It has yet to be determined whether the prevalence is higher in the general population and in patients on peritoneal dialysis. PMID- 27657184 TI - Prevalence of cervical cancer and associated mortality in Grenada, 2000-2010. AB - Objective To assess cervical cancer prevalence and associated mortality in Grenada, West Indies during 2000-2010. Methods Records of visits to hospital and clinical facilities were obtained from the histopathology laboratory of the Grenada General Hospital. Records were de-identified and electronically compiled. Cervical cancer prevalence was assessed via cross-sectional analysis of this secondary data. Of a total 12 012 records, 2 527 were selected for analysis using sampling without replacement. Cases were matched to corresponding patient data from death registries, where possible, and used to calculate associated mortality rates. Results The observed prevalence of cervical cancer was 52.4 per 100 000 women (ages 15 and above). The highest rates of cervical cancer occurred in the 35-44 age group, with the second highest among 45-64-year-olds. A total of 65 deaths were attributable to cervical cancer during 2000-2010, more than 50% of which were among women > 65 years old. The observed mortality rate was 16.7 per 100 000, almost twice the rate estimated by WHO for the region. Conclusions This study demonstrates the need for a comprehensive cervical cancer-screening program in Grenada. Results should contribute to informing future studies on how to appropriately generate and execute public health policy for education, screening, prevention, and control of cervical cancer in Grenada. PMID- 27657185 TI - Energy interventions that facilitate sustainable development and impact health: an overview of systematic reviews. AB - Objective To inform policy by providing an overview of systematic reviews on interventions that facilitate sustainable energy use and have a positive impact on health. Methods Systematic review methods were used to synthesize evidence from multiple systematic reviews and economic evaluations through a comprehensive search of 13 databases and nine websites based on a pre-defined protocol, including clear inclusion criteria. Both grey and peer-reviewed literature published in English, Spanish, and Portuguese during the 17 years from January 1997 - January 2014 was included. To classify as "sustainable," interventions needed to aim to positively impact at least two dimensions of the integrated framework for sustainable development and include measures of health impact. Results Five systematic reviews and one economic evaluation met the inclusion criteria. The most promising interventions that impacted health were electricity for lighting and other uses (developing countries); improved stoves for cooking and health and/or cleaner fuels for cooking (developing countries); and household energy efficiency measures (developed countries). These interventions also had potential environmental and economic impacts. Their cost-effectiveness is not known, nor is their impact on health inequalities. Conclusions What is needed now is careful implementation of interventions where the impacts are likely to be positive but their implementation needs to be rigorously evaluated, including possible adverse impacts. Care needs to be taken not to exacerbate health inequalities and to consider context, human behavior and cultural factors so that the potential health benefits are realized in real-life implementation. Possible impact on health inequalities needs to be considered and measured in future primary studies and systematic reviews. PMID- 27657186 TI - [Development of an electronic device to organize medications and promote treatment adherence]. AB - This article describes the development of an electronic prototype to organize medications - the Electronic System for Personal and Controlled Use of Medications (Sistema Eletronico de Uso Personalizado e Controlado de Medicamentos, SUPERMED). The prototype includes a drawer containing 1 month's supply of medicines, sound and visual medication timers, and a memory card for recording the times when the box was opened/closed (scheduled and unscheduled). This information is later transferred to a computer. Evolutionary prototyping was used to develop SUPERMED with the Arduino platform and C programming. To read alarm and box opening/closing data, software was developed in Java. Once the alarms are programmed (ideally by a health care professional), no additional adjustments are required by the patient. The prototype was tested during 31 days by the developers, with satisfactory functioning. The system seems adequate to organize medications and facilitate adherence to treatment. New studies will be carried out to validate and improve the prototype. PMID- 27657188 TI - Exploring the Value of a Podiatric Consult in Palliative Wound Care. PMID- 27657187 TI - The synthesis of OspD3 (ShET2) in Shigella flexneri is independent of OspC1. AB - Shigella flexneri is a Gram-negative pathogen that invades the colonic epithelium and causes millions of cases of watery diarrhea or bacillary dysentery predominately in children under the age of 5 years in developing countries. The effector Shigella enterotoxin 2 (ShET2), or OspD3, is encoded by the sen or ospD3 gene on the virulence plasmid. Previous literature has suggested that ospD3 is in an operon downstream of the ospC1 gene, and expression of both genes is controlled by a promoter upstream of ospC1. Since the intergenic region is 328 bases in length and contains several putative promoter regions, we hypothesized the genes are independently expressed. Here we provide data that ospD3 and ospC1 are not co-transcribed and that OspC1 is not required for OspD3/ShET2 function. Most importantly, we identified strong promoter activity in the intergenic region and demonstrate that OspD3/ShET2 can be expressed and secreted independently of OspC1. This work increases our understanding of the synthesis of a unique virulence factor and provides further insights into Shigella pathogenesis. PMID- 27657189 TI - Hedgehog Signaling Activation in Hepatic Stellate Cells Promotes Angiogenesis and Vascular Mimicry in Hepatocellular Carcinoma. AB - Previous studies have established that hedgehog (Hh) signaling mediates tumor stroma interaction and promotes hepatocellular carcinoma progression. Here, we demonstrated that activation of Hh signaling in hepatic stellate cell (HSC) line LX-2 by Huh-7-derived sonic Hh led to increased secretion of angiogenic factors and promoted angiogenesis in vitro. The activated LX-2 also enhanced vascular mimicry of hepatoma cells. Furthermore, co-injection of Huh-7 and LX-2 significantly accelerated tumor growth with enhanced angiogenesis compared with Huh-7 alone, which could be partly abrogated by Hh signaling inhibitor. Collectively, our data showed that paracrine Hh signaling mediated pro-angiogenic function of HSC and enhanced hepatoma growth. PMID- 27657190 TI - Internet use and well-being in later life: a functional approach. AB - OBJECTIVES: This study aimed at exploring the Internet's role in supporting subjective well-being in later life by applying a functional approach, namely, simultaneously but separately examining each of the principal online functions common among older adults (interpersonal communication, information, task performance and leisure). METHODS: Data were collected online from 306 Internet users aged 50 years and over. Subjective well-being was measured according to indicators of depression and life satisfaction. RESULTS: Interpersonal communication and information seeking were the most commonly used Internet functions, followed by task performance; use for leisure and recreation was significantly less prevalent. All four online functions were positively correlated with life satisfaction, and task performance and leisure were negatively correlated with depression. After controlling for sociodemographic variables, only leisure associated significantly with the well-being measures. DISCUSSION: These findings revealed a paradoxical situation in which the most beneficial use of the Internet is the least popular. PMID- 27657191 TI - Imaging Appearance of Lymphatic Malformations. PMID- 27657192 TI - Pleasure in using adaptive cruise control: A questionnaire study in The Netherlands. AB - OBJECTIVE: Adaptive cruise control (ACC), a technology that allows for automated car following, is becoming increasingly prevalent. Previous surveys have shown that drivers generally regard ACC as pleasant but that they have to intervene when the ACC reaches its operational limits. The former research has been mostly concerned with specific car brands and does not fully reflect the diversity of ACC types in traffic today. The objective of the present research was to establish the determinants of pleasure in using ACC. METHODS: A 55-item online questionnaire was completed by Dutch users of diverse ACC systems. RESULTS: Respondents (N = 182) rated their ACC highly, with a mean score of 8.0 on a scale from 1 (extraordinarily negative) to 10 (extraordinarily positive) and were most pleased with ACC on high-speed roads and in low-density traffic. Moreover, the findings point to specific operational limits such as associated with cut-in situations. Pleasure was greater for the types of ACC that are able to decelerate to a full stop, according to 48% of our sample. An analysis of the free-response items indicated that respondents who were displeased with ACC mentioned its occasional clumsiness and the dangerous situations it may evoke, whereas those who were pleased with ACC valued the complementarity of human and machine and emphasized the roles of responsibility and experience in using ACC. CONCLUSION: Pleasure in using ACC is a function of both technological advances and human factors. PMID- 27657193 TI - Does Abstinence From Ejaculation Before Prostate MRI Improve Evaluation of the Seminal Vesicles? AB - OBJECTIVE: The purpose of the present study is to determine whether abstinence from ejaculation before undergoing multiparametric prostate MRI increases seminal vesicle (SV) volume and therefore improves diagnostic interpretation of the SVs. MATERIALS AND METHODS: This retrospective study included 238 patients who underwent 3-T MRI of the prostate over a 4-month period. Patients were requested to complete a questionnaire that asked how long it had been since their last ejaculation (i.e., < 3 days vs >= 3 days). Forty-two patients (mean patient age, 62.0 years) indicated that it had been less than 3 days since their last ejaculation and were designated as group 1, whereas the remainder indicated an interval of 3 days or more since their last ejaculation. A group of 42 age matched subjects (mean patient age, 62.1 years) were randomly selected from the remaining 196 patients and were designated as group 2. SV volumes were measured manually. Two radiologists who were blinded to group assignment and patient characteristics scored the right and left SVs separately to determine diagnostic interpretability, which was scored on a 3-point scale as follows: a score of 1 denoted that the SVs were not dilated and the score was nondiagnostic, a score of 2 indicated that the SVs were not dilated but the score was diagnostic, and a score of 3 denoted that the SVs were dilated and the score was diagnostic. Volume differences and interpretability scores were analyzed using a t test. Interobserver agreement was analyzed using the Cohen kappa statistic. A separate analysis was performed to evaluate differences in diagnostic interpretability for patients 60 years and younger versus patients older than 60 years, by use of the chi-square test and relative risk ratio analysis. RESULTS: The right, left, and total SV volumes for group 1 were 3.1 mL, 2.9 mL, and 6.0 mL, respectively, whereas those for group 2 were 4.7 mL, 4.1 mL, and 8.8 mL, respectively (p = 0.011). The mean interpretability scores for group 1 and group 2 were 2.0 and 2.5, respectively. For group 1, reader 1 and reader 2 assigned a nondiagnostic score for 10 and 13 patients, respectively, whereas for group 2, they assigned a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.03, for reader 2). For men in group 1 who were older than 60 years, reader 1 and reader 2 gave a nondiagnostic score for nine and 11 patients, respectively; whereas for men in group 2 who were older than 60 years, the readers gave a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.05, for reader 2). CONCLUSION: For men older than 60 years, abstinence from ejaculation for 3 or more days before undergoing MRI examination resulted in larger SV volumes and lower rates of nondiagnostic evaluation and therefore might improve evaluation of SV invasion on multi parametric MRI. The difference is less striking in men 60 years and younger. PMID- 27657196 TI - New practice boundaries. AB - Nurse practitioners are still considered a slight oddity - not quite mainstream nursing, more the subject of a few pilots. PMID- 27657197 TI - Wound care: A problem solving approach. AB - The aim of this Learning Unit is to enable you to develop your knowledge, observational and problem-solving skills in relation to wound management so that you can deliver more effective, holistic care to patients and clients. PMID- 27657195 TI - Phenogenotypic Characterization of Escherichia coli O157:H7 Strains Isolated from Cattle at Slaughter. AB - Shiga toxin-producing Escherichia coli (STEC) O157:H7 was isolated from 30 (4%) of 744 cattle hide swab samples collected at Estonian slaughterhouses within a 3 year monitoring program of zoonotic pathogens. The isolates were characterized by determining the presence of STEC main virulence factors, the antimicrobial resistance profiles, and the genetic relatedness by pulsed-field gel electrophoresis (PFGE). Thirteen strains carried the stx2 gene alone and 17 both the stx1 and stx2 genes. The most frequently detected stx subtype was stx2c, occurring alone (n = 12) or in combination with subtype stx1a (n = 13). All isolates harbored the intimin-coding eae gene and produced enterohemolysin. Twelve isolates (40%) showed resistance to at least one of the 14 antimicrobials and the isolates were predominantly resistant to streptomycin, sulfamethoxazole, and ampicillin. No extended-spectrum beta-lactamase-producing isolates were detected. PFGE characterization of the isolates showed an overall similarity higher than 75%, and four clusters based on 100% similarity were revealed. PMID- 27657194 TI - Genetic predisposition to elevated levels of C-reactive protein is associated with a decreased risk for preeclampsia. AB - OBJECTIVE: To examine the association between genetic predisposition to elevated C-reactive protein (CRP)and risk for preeclampsia using validated genetic loci for C-reactive protein. METHODS: Preeclampsia cases (n = 177) and normotensive controls (n = 116) were selected from live birth certificates to nulliparous Iowa women during the period August 2002-May 2005. Disease status was verified by the medical chart review. Genetic predisposition to CRP was estimated by a genetic risk score on the basis of established loci for CRP levels. Logistic regression analyses were used to evaluate the relationships between the genotype score and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. RESULTS: The genetic risk score (GRS) related to higher levels of CRP demonstrated a significantly decreased risk of preeclampsia (OR 0.89, 95% CI 0.82 0.96). When the GRS was analyzed by quartile, an inverse linear trend was observed (p = 0.0006). The results were similar after adjustments for the body mass index (BMI), smoking, and leisure-time physical activity. In the independent replication population, the association with the CRP GRS was also marginally significant (OR 0.97, 95% CI 0.92, 1.02). Meta-analysis of the two studies was statistically significant (OR 0.95, 95% CI 0.90, 0.99). CONCLUSION: Our data suggest an inverse, counterintuitive association between the genetic predisposition to elevated levels of CRP and a decreased risk of preeclampsia. This suggests that the blood CRP level is a marker of preeclampsia, but it does not appear to be a factor on the causal pathway. PMID- 27657198 TI - President's anger at devalued skills. AB - RCN President June Clark has spoken of her 'burning anger' at the 'continued devaluation' of nursing skills in the health service. PMID- 27657199 TI - ? AB - In the box seat: Giselle Ritchie, centre, attending an 'extra access performance' at the Royal Opera House, Covent Garden. Ms Ritchie is shown with Institute of Health Services Management Director Ray Rowden, who devised the scheme to improve wheelchair access to the theatre, and Health Secretary Virginia Bottomley. PMID- 27657200 TI - RGM job descriptions raise nursing optimism. AB - Optimism grew last week that nursing will continue to play a key role in the intermediate tier of the NHS, with the circulation of job descriptions for the new regional general managers' posts which make clear reference to 'continued support for the development of nursing practice'. PMID- 27657201 TI - Pay rise will be up to 3 per cent. AB - A government decision on nurses' pay is expected within days, with the Prime Minister expected to approve a rise of tip to 3 per cent, but linked to efficiency savings. PMID- 27657202 TI - DoH launches 'front-line' nurse projects. AB - The Royal College of Nursing has welcomed government funding for ten new nurse practitioner projects, but called for the initiatives to be more than one-offs'. PMID- 27657203 TI - Allitt report may blame staff. AB - The findings of the Clothier Enquiry into the murder of four children by nurse Beverly Allitt were handed to the Health Secretary last week amid claims' that Both nurses and doctors on Ward Four at Grantham General Hospital had been criticised. Mrs Bottomley could release the report today, but may delay release until next month. Unison spokesperson Bob Quick said: I think our major concerns are that the two doctors and two nurses being mentioned in the report really can't be expected to take the blame for all that went wrong on Ward Four in Grantham Hospital. Important issues relating to staffing levels, recruitment procedures and communications between the ward and senior levels also need highlighting. ' 'The Royal College of Nursing said: 'We will actively oppose scapegoating of any individual. We are also keen to see if all issues raised in our own evidence are fully addressed.' PMID- 27657204 TI - L80m health promotion scheme is 'making little difference'. AB - Claims that practice nurses in an L80 million health promotion scheme are making little difference to overall health figures have been disputed by the RCN and the Health Visitors' Association. PMID- 27657205 TI - Call for strategy. AB - A coordinated nurse training strategy to tackle the current short-term' approach to student numbers is needed, RCN General Secretary Christine Hancock has said. PMID- 27657206 TI - ? AB - Here's one I made earlier: Marie Bray and Graham Bickers of Health Promotion Services with papier mache models devised for use in training health professionals in developing countries and displayed at an exhibition on Developing World Health. Ms Bray recently returned from Nigeria where the models were used to train health workers in the basics of obstetrics. Details on making 'Obsteteach' models from Ms Bray on 0a83 332121. PMID- 27657208 TI - 'Significant improvement' in damages claims. AB - The RCN's legal department has won almost L7million in damages for members over the last five years, Council heard. PMID- 27657207 TI - High Court action threat forces climbdown. AB - The threat of High Court action by the RCN to block a hospital skill mix review has forced managers at Frimley Park Hospital Trust in Surrey to back down from their refusal to negotiate with unions. PMID- 27657209 TI - RCN changes rules on subs increases. AB - Royal College of Nursing members will no longer be balloted on proposed rises in annual subscriptions, RCN Council agreed last week. PMID- 27657211 TI - Wide-ranging agenda for congress. AB - Calls for the age of consent for homosexual men to be reduced to 16 will be discussed at this year's RCN Congress as part of a wide-ranging agenda revealed at last week's Council meeting. PMID- 27657210 TI - Pilot sabbatical posts planned. AB - The first student sabbatical posts in the NHS are to be set up by the RCN, Council agreed last week. PMID- 27657212 TI - ? AB - The Royal College of Nursing Dialysis and Transplant Nurses Forum celebrated its 21st anniversary with the cutting of a special celebratory cake at its meeting and study day in Manchester last week. Several former honorary officers were present, including the College's current Director of Policy and Practice, Liz Winder, a past Chair of the forum. PMID- 27657215 TI - NHS managers urged to help staff cope with stress at work. AB - Managers must help stressed health care staff to cope with their work if the NHS is to be seen as a healthy employer, chief executives at a 'Working Well in the NHS' conference were told last week. PMID- 27657214 TI - ? AB - Bulimia sufferer Joanna Goodfellow is staging an exhibition of photographs portraying the distorted perceptions she has of her body and the self-hatred she sometimes feels. Joanna has suffered from an eating disorder for the past five years and wants people to understand the 'frustration and anger' she feels when she looks at her bod)'. The exhibition, at the Barbican Theatre in Plymouth, runs until February 12. PMID- 27657216 TI - Hearings spark scapegoating fear. AB - Unions warned last week that nurses at Broadmoor Hospital could become victims of management 'scapegoating' after revelations that six staff members face disciplinary action. PMID- 27657217 TI - Number of day cases doubled. AB - The number of day cases dealt with in NHS hospitals has topped two million, more then doubling the rate ten years ago. PMID- 27657218 TI - Government accepts report on enhanced role for midwives. AB - Midwifery unions have given their overwhelming backing to the government's decision to implement in full the recommendations of the Changing Childbirth report. PMID- 27657219 TI - ENB launches midwifery fact file. AB - ENB Chief Executive Tony Smith used the conference to launch the Board's Midwifery Fact File, which aims to inform midwives on the ENB's work in midwifery education, supervision and practice. PMID- 27657220 TI - Placements 'good for students'. AB - Student midwives should undergo a series of placements in non-midwifery areas such as gynaecology, surgery and mental health to broaden their experience and improve their communication skills, the conference was told. PMID- 27657222 TI - ? AB - Former Chief Nurse Dame Kathleen Raven at the ceremony to mark her admission to the Court of Patrons of the Royal College of Surgeons. The honour was bestowed upon her in recognition of her contribution to the education of surgeons. Dame Kathleen's brother Ronald, a distinguished surgeon, was a member of RCS Council and she established an educational trust in his memory after his death. PMID- 27657223 TI - Fund will aid community teams. AB - Scottish community nurses will benefit from a new Primary Care Development Fund announced by Scottish Office Health Minister Lord Fraser. PMID- 27657224 TI - Survey to look at all aspects of nursing staff careers. AB - An important survey on nurses' careers in the NHS begins this week. It will be undertaken by the Policy Studies Institute, an independent think tank. PMID- 27657225 TI - A&E waits are 'due to nurse sickness'. AB - A Welsh consultant has blamed long waiting times in A&E departments on high rates of sickness among nurses. PMID- 27657226 TI - World news. AB - Ireland Irish psychiatric nurses have won a significant victory in their fight to secure full pay for nurses who are injured while on escort duties. PMID- 27657227 TI - Elderly people more likely to hide alcohol use. AB - Elderly people are more likely to conceal alcohol use, more vulnerable to its adverse effects and less likely to be diagnosed as misusing alcohol than younger people, according to a new study. PMID- 27657228 TI - Family life ruined by eczema, says report. AB - Four out of five adults with severe, chronic eczema say their family life is ruined by the condition, a new survey has revealed. PMID- 27657229 TI - Midwives must do more to stop pregnant smokers. AB - Midwives are not doing enough to discourage pregnant women from smoking, according to a report by the Royal College of Midwives and the Health Education Authority. PMID- 27657231 TI - Blood group, Hpylori and gastric ulcer linked. AB - Researchers believe they have unravelled one of the mysteries about why people with group O blood are more prone to gastric ulceration. PMID- 27657232 TI - Laparoscope better for patients, but dearer. AB - Laparoscopic cholecystectomy results in less postoperative dysfunction, shorter hospital stay and quicker return to normal activities, compared to mini- laparotomy. But it is more expensive. PMID- 27657233 TI - Brewer's yeast good for C difficile diarrhoea? AB - Brewer's yeast tablets may be a useful therapy for Clostridium difficilediarrhoea in patients who do not respond to conventional treatment. PMID- 27657234 TI - Predicting the risk of postoperative delirium. AB - Using data available preoperatively, it is possible to predict which patients are at risk of the development of delirium. PMID- 27657235 TI - Antibiotics, gastric acid and salmonella infection. AB - The risk of infection with salmonella is increased in people taking H, antagonists, Nottingham researchers suggest. PMID- 27657236 TI - After the ceremony. AB - Following a short period of disbelief, I was very pleased to be chosen as one of the winners of the Clinical Practice and Management Awards. I had found the ten part series on management issues both interesting and easily applicable to my practice, but as for winning the award, I did not feel I stood a very good chance. PMID- 27657237 TI - Charter aids clients nursing grudge. AB - I fully support Christopher Goodall's call for a Nurse's Charter to protect nurses against aggressive patients (What about our rights? Viewpoint, December 8). PMID- 27657239 TI - ? AB - " I wouldn't complain about being in a Mixed ward If I were you I'm in a mixed corridor?" PMID- 27657238 TI - Sentenced to blush for having dyslexia. AB - I was most interested to read your student article on dyslexia (Dyslexia spells trouble, No Limits supplement, January' 5) as I, too, have suffered similar problems at the hands of the ; nursing profession, When I was studying for my A levels, I was referred by my further education college to a clinical psychologist, to be tested for dyslexia. PMID- 27657240 TI - RCN students are local heroes. AB - I have to respond to the student who left the RCN and joined Unison, claiming that the RCN lacked forward thinking and local representation for students (Power play, January 19). PMID- 27657241 TI - Bravo for return of the pink panzer. AB - I write to express my considerable anger after reading Graham Pink's account of being a United Kingdom Central Council committee member (Behind dosed doors, January 12). PMID- 27657243 TI - Information exchange. AB - I cannot get support for getting onto a conversion course. I am currently an enrolled nurse working on an NHS hospital's nurse bank. PMID- 27657242 TI - Feet on ground and skirts a foot higher. AB - As a very old member of the nursing profession, may I add to the great uniform debate? PMID- 27657244 TI - Vents for spleen and ease of lifting. AB - Why does health minister Brian Mawhinney think he needs us to ditch our 'outmoded' and 'sexist' uniforms, as reported in the Sunday Times late last year? PMID- 27657246 TI - Lights, camera, traction! AB - Hi there, health care workers. Remember I told you that the BBC was coming to film my unit, giving my New Nursing Model the nationwide media coverage it deserves? PMID- 27657245 TI - A leader with a common touch. AB - One of nursing's leading lights of the Sixties and Seventies, self-styled 'ancient Brit' Beatrice Brysson Whyte OBE. FRCN, died on November 27 last year aged 72. Brysson Whyte, as she will be remembered by her friends and former students, spent the years after her retirement in 1981 working with and for the elderly. PMID- 27657247 TI - Nice vital statistics SPSS/PC + and SPSS for Windows: A Beginner's Guide to Data Analysis, 2nd edition. Foster JJ et al 1993 Price: Supplier: Computer Manuals , Birmingham. L14.95 021-706-6000. AB - Any nurse who needs to deal with quantitative data soon needs a computer program to handle it. The SPSS program has been around for a long time in various versions, from mainframe to Windows. PMID- 27657248 TI - Hardship and health in women's lives Hardship and health in women's lives H Graham Harvester Wheatsheaf 222pp L10.95 0-7450-1264-7. AB - Hardship and hlealth in Women's Lives should be compulsory reading for politicians, sociologists and all in the caring professions. It is not for casual reading. PMID- 27657250 TI - Falls in the elderly Falls in the elderly JH Downton Edward Arnold 158pp L16.95 0 340-54848-7 [Formula: see text]. AB - With the increasing need to promote health and care in the community, Falls in the Elderly should be a useful text. Joanna Downton, a consultant geriatrician, provides 10 individually referenced chapters, beginning with the epidemiology of falls, ranging through consequences, management, nursing aspects and the prevention of falls, and ending with suggestions for the future and an index. PMID- 27657249 TI - Readings in Family Nursing G D Wegner Readings in Family Nursing R J Alexander J B Lippincott 420pp L24.95 0-397-55033-2. AB - Readings in Family Nursing is divided into four parts and contains selected papers and articles from nursing journals (1989-1991). The formats vary: some are case studies, some research and some are issues of theory development. Part One concentrates extensively on theory development in family health nursing from the child to the elderly person, regarding the health needs within the family. Among the various models discussed are the Roy Adaptation model, Orem's, Parse's theory and Newman's systems model. Family nursing is practised at three levels: individual, interpersonal and system. PMID- 27657251 TI - Listings. AB - International March 23-25 The theme of the third annual conference of the Quality of Nursing Worklife Research Unit at the University of Toronto and McMaster University will be 'Global transitions in the worklife/workplace of nurses'. It will be held at the Sheraton Hamilton, Ontario, Canada. For payments postmarked before February 7 the fee is $250. Details from Dyanne Semogas, Research Co ordinator, Quality of Nursing Worklife Research Unit, School of Nursing, McMaster University, HSC-2J12A, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. Ontario, Canada L8n 3Z5 Tel (905) 525-9140, ext 22581. PMID- 27657252 TI - Nicely conceived, but poorly- timed. AB - The term 'mandatory periodic refreshment' has been bandied around in nursing for some years now. It has been widely misinterpreted by nurses and created a climate of fear that professional updating will be rigidly enforced from the top. A cloud of uncertainty about when and how mandatory refreshment would be implemented has added to feelings of uneasiness. While many recognise that the issue needs to be addressed, few have found comfort in the idea that they might be 'mandated' to do so. PMID- 27657253 TI - Bribery allegations under investigation. AB - Four Broadmoor nurses were suspended on full pay last week as police investigated bribery allegations at the secure psychiatric hospital. PMID- 27657254 TI - Royal Colleges draw up NHS safeguards. AB - The Nursing and Medical Royal Colleges have secretly been drawing up a Lords' amendment to the NHS Bill which could present Health Secretary Kenneth Clarke with the first real legislative challenge to his reforms. PMID- 27657255 TI - ? AB - Jersey nurse Kathy Harvey has launched a campaign on the island to collect warm clothing for children in Romania. She started the project after seeing television reports about conditions at a mental handicap hospital in the north of the country. See News item on page 7. PMID- 27657256 TI - PREPP proposes third level of registration. AB - Far-reaching proposals which could dramatically change the way nurses maintain their competence after qualifying were launched for debate this week. PMID- 27657257 TI - Serious delay forecast before ICN readmission. AB - Despite sweeping political changes in South Africa, it could be years before the country's nurses can rejoin the International Council of Nurses, the ICN said last week. PMID- 27657258 TI - Hancock warns of threat to skills. AB - Community nursing skills are in danger of becoming lost under the Government's community care proposals, the Royal College of Nursing warned a Parliamentary committee last week. PMID- 27657259 TI - Role of Review Body in danger. AB - The Review Body for senior nurses' salaries will have less power in future if management proposals announced last week go ahead. PMID- 27657260 TI - Appeal for funds to set training programme. AB - A group of mental handicap nurses are appealing for help in funding their planned trips to Romania where they will use their clinical expertise to help set up a new training development programme for nurses. PMID- 27657261 TI - Food poisoning linked to morale. AB - An outbreak of food poisoning in hospital as been blamed on poor food handling by staff suffering low morale caused by low pay, overwork and bad management -- a catering problem engendered by competitive tendering policies. PMID- 27657262 TI - ACE campaigns to ensure elderly needs are not neglected by P2000. AB - The Royal College of Nursing Association for Care of the Elderly (ACE) is to launch a 1990 campaign to see that Project 2000 courses do not neglect elderly health needs. PMID- 27657263 TI - Early successes in RCN appeals campaign. AB - Success in two clinical grading appeals at regional level has persuaded the Royal College of Nursing that the process can bring results. PMID- 27657265 TI - Squeeze predicted on community funding. AB - There is a real risk that community care spending may be squeezed out of local authority spending, Toby Harris, leader of Haringey Council, has warned. PMID- 27657264 TI - ? AB - London commuters got a special Valentine's day message when district nurses from Mid-Surrey Health Authority had a heart-to-heart' about unhealthy lifestyles. A quarter of all deaths in the district are caused by heart disease. PMID- 27657267 TI - Nurses could act as entrepreneurs. AB - Nurses could become business entrepreneurs and 'sub-contract' nursing services out to local authorities under the Government's NHS reforms, nurse managers have been told. PMID- 27657268 TI - Major survey aims to monitor change. AB - The largest ever survey of mental handicap nurses was launched last week in a bid to discover how the speciality is evolving for the future. PMID- 27657269 TI - ENB to continue its fight for control. AB - The English National Board (ENB) has made its bid to control the future funding of nurse education in its submission to the Government on both the Peat Marwick McLintock (PMM) report and Working Paper 10. PMID- 27657270 TI - Staff must be involved. AB - Nursing staff must be allowed to define quality in internal market contracts, a unit general manager declared last week. PMID- 27657273 TI - World news. AB - Hong Kong Vietnamese women in Hong Kong's refugee camps are being intimidated into using contraceptive injections of Depo Provera even after they have suffered severe bleeding, a Danish relief worker has claimed. PMID- 27657274 TI - ? AB - Romania Britain is sending L1 million worth of syringes to Romania following diclosures of a major AIDS epidemic among its babies and children. PMID- 27657275 TI - Parliament. AB - International protests are flooding in to Britain over threats to close the world famous Cassel Hospital in Richmond, London, a Conservative MP has claimed (see Nursing Standard, February 14-20, pp20-21). PMID- 27657277 TI - Coping with sleeping difficulties. AB - Patient information leaflets and surgery posters on how to cope with sleeping difficulties are now available from Rhone-Poulenc Pharmaceuticals - who recently launched the non-benzodiazepine sleeping tablet, Zimovane. PMID- 27657278 TI - Breakthrough in leg ulcer treatment. AB - A leg ulcer clinic at Riverside District Health Authority has found that using a series of four bandages can heal the majority of leg ulcers within 12 weeks. PMID- 27657279 TI - Testicular cancer fear over vasectomy. AB - Vasectomy may accelerate the development of testicular cancer, a new Scottish hospital study has suggested. PMID- 27657280 TI - Dressing cavity wounds. AB - Cavity wounds should be dressed with specially developed pastes and gels rather then the traditional ribbon gauze dressing, a clinical nurse specialist has claimed. PMID- 27657281 TI - Stress management awareness. AB - Medical and nursing professions must be adequately prepared to deal with raised public awareness of stress management in prevention of coronary heart disease, a nurse specialist has warned. PMID- 27657282 TI - Colour coding needed for eye solutions. AB - Solutions for use in the eyes should be packaged in bottles with a distinctive shape and coloured cap, doctors from London say. PMID- 27657283 TI - Risks from endometrial resection. AB - Fluid balance must be closely monitored during endometrial resection, ideally using a continuous flow instrument. PMID- 27657284 TI - Treatment of cyclical mastalgia. AB - Bromocriptine can significantly improve the symptoms of cyclical mastalgia, researchers from Manchester and Turin say. PMID- 27657285 TI - Giving up smoking is good for women too. AB - Stopping smoking reduces the risk of myocardial infarction in women, regardless of how heavily or for how long they previously smoked. PMID- 27657286 TI - Risk of ulceration from foscarnet. AB - Foscarnet is increasingly being used in the treatment of cytomegalovirus (CMV) and herpes simplex virus (HSV) in people with AIDS but two recent reports suggest the drug may cause genital ulcers. PMID- 27657287 TI - Opening race. AB - Back in the mid 1970s, South Africa's nursing profession became isolated from the rest of the world. Officially, the South African Nursing Association (SANA) withdrew its membership from the International Council of Nurses (ICN). But the threat of expulsion no doubt hastened their departure. PMID- 27657288 TI - Unkind cuts. AB - The Government's failure to fund fully the nurses' pay award again this year comes at a time when many health authorities, particularly in London, are seriously overspent on this year's budgets. PMID- 27657289 TI - Guidance on use of logos. AB - I am writing to express my concern regarding the community nurses who are driving around with company logos on their cars. In my opinion this amounts to breaching the United Kingdom Central Council for Nursing, Midwifery and Health Visiting's Code of Professional Conduct. PMID- 27657290 TI - Using logos for recruitment. AB - I read with much interest your news article 'Company logo sparks sponsorship move' (Nursing StandardJanuary 31 - February 6). PMID- 27657291 TI - The end justifying the means. AB - In response to the news item in Nursing Standard (January 31-February 6) entitled 'Company logo sparks sponsorship move', I find nothing wrong with nurses driving around with company logos on their cars. PMID- 27657292 TI - The trouble with teenagers. AB - I am writing in response to the article, 'Teenage troubles' (Nursing Standard January 31 - February 6). I feel angered and concerned that as usual the plight of the community attracting qualified staff is not being addressed as part of this or previous campaigns. PMID- 27657293 TI - A case for misconduct. AB - In response to Jean Gray's article regarding misconduct, 'A long wait for justice' (Nursing Standard January 31-February 6) in which Reg Pyne comments about the 'profession needing to be better informed about the nature of misconduct', concern may be created about what actually constitutes misconduct. PMID- 27657294 TI - The disgraceful hearing delays. AB - I am writing in response to your feature on professional misconduct which highlights the disarray in which the profession finds itself. How disgraceful chat nurses facing charges are having to wait for lengthy periods before their complaints are dealt with. PMID- 27657295 TI - Nursing memories. PMID- 27657296 TI - Comic strip hoot. AB - I read with interest the article 'Teenage troubles'. Obviously the profession is becoming increasingly aware of the shortfall in nurse recruitment and the problems this is going to cause. PMID- 27657297 TI - Fiction file. PMID- 27657298 TI - Teenage troubles. AB - I am writing with reference to the feature in Nursing Standard (January 31 - February 6) which states that the Government has spent approximately 'L644 per potential recruit'. PMID- 27657299 TI - Clearing the air. AB - I was distressed to read your article in World News (Nursing Standard January 31 to February 6) that one fifth of the World's people breath polluted air that fails to meet the World Health Organization's standards. The staggering number of deaths (50,000 per year) is amazing as is the fact that breathing air in Bombay is equivalent to the smoking of I ten cigarettes a day. PMID- 27657300 TI - Preparing for the future. AB - Nursing is undergoing radical and fundamental changes. The impact of Project 2000 and the recruitment and retention of professional staff have profound implications for the delivery of patient care. All this is taking place in a service under threat from the demographic 'black hole' - the dearth of young people who will work in the health service due to the low birth rate in the early 1970s. We believe the first level registered nurse (RN) has to assume a positive role if the profession is to play its full part in facing the challenges health care will bring in the future. PMID- 27657301 TI - The A-Z of Stoma Care. AB - Modular Teaching Package: 4 Videos (approximately 63 mins total running time); Workbooks; Flip chart Available free only from: Convatec Ltd Squibb House, 141 149 Staines Road, Hounslow, Middx TW3 3JA. PMID- 27657302 TI - Becoming and being old B Bytheway et al Becoming and being old SAGE Publications 184pp L19.95 0-8039-8170-8. AB - Becoming and Being Old is a collection of papers from a variety of eminent sociologists on a range of issues affecting people in midlife and onwards. PMID- 27657303 TI - Change in the 1990s. AB - The last weeks of the 1980s were marked by rapid and radical changes in Eastern Europe with the acknowledgement of the rights of individuals within the responsibilities of democratic government. At the same time, the rights of children were being acknowledged at both national and international levels. The signing of the United Nations 'Convention of the Rights of the Child', and the 1989 Children Act provide the legislative framework that could mark a watershed in the recognition of children as individuals with rights and needs. PMID- 27657304 TI - Fatima Mayet with another in the microbiological series. PMID- 27657305 TI - Don't sleep on it: Less sleep reduces risk for depressive symptoms in cognitively vulnerable undergraduates. AB - The current research tested a new theory of depression that integrates work on sleep and cognition. In general, good sleep is essential for physical and mental health. However, we theorize that sleep can actually increase risk for depressive symptoms in cognitively vulnerable individuals. This is because the negative cognitions generated by these individuals are strengthened and consolidated each night during sleep. Three studies were conducted to test this theory. Studies 1 (n = 134) and 2 (n = 47) used prospective designs and showed that undergraduates with high, but not low, levels of cognitive vulnerability were most likely to exhibit increases in depressive symptoms when sleeping well as operationalized by self-reported quality and objectively measured duration (via actigraphy). Study 3 (n = 40) used an experimental design and provides the first causal evidence that it may be possible to prevent future depressive symptoms in cognitively at-risk undergraduates by restricting their sleep during times of high perceived stress. (PsycINFO Database Record PMID- 27657306 TI - The broadcast of shared attention and its impact on political persuasion. AB - In democracies where multitudes yield political influence, so does broadcast media that reaches those multitudes. However, broadcast media may not be powerful simply because it reaches a certain audience, but because each of the recipients is aware of that fact. That is, watching broadcast media can evoke a state of shared attention, or the perception of simultaneous coattention with others. Whereas past research has investigated the effects of shared attention with a few socially close others (i.e., friends, acquaintances, minimal ingroup members), we examine the impact of shared attention with a multitude of unfamiliar others in the context of televised broadcasting. In this paper, we explore whether shared attention increases the psychological impact of televised political speeches, and whether fewer numbers of coattending others diminishes this effect. Five studies investigate whether the perception of simultaneous coattention, or shared attention, on a mass broadcasted political speech leads to more extreme judgments. The results indicate that the perception of synchronous coattention (as compared with coattending asynchronously and attending alone) renders persuasive speeches more persuasive, and unpersuasive speeches more unpersuasive. We also find that recall memory for the content of the speech mediates the effect of shared attention on political persuasion. The results are consistent with the notion that shared attention on mass broadcasted information results in deeper processing of the content, rendering judgments more extreme. In all, our findings imply that shared attention is a cognitive capacity that supports large-scale social coordination, where multitudes of people can cognitively prioritize simultaneously coattended information. (PsycINFO Database Record PMID- 27657307 TI - Intraoperative Perfusion Computed Tomography in Carotid Endarterectomy: Initial Experience in 16 Cases. AB - BACKGROUND This study aimed to evaluate the changes in perfusion computed tomography (PCT) parameters in carotid endarterectomy (CEA), and to discuss the use of intraoperative PCT in CEA. MATERIAL AND METHODS Sixteen patients with carotid stenosis who also underwent CEA with intraoperative CT were recruited in this study. We calculated quantitative data on cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and the relative parameter values, including relative CBF (rCBF), relative CBV (rCBV), and relative TTP (rTTP). The role of PCT was assessed and compared to conventional monitoring methods. RESULTS There were no significant differences in any of the parameters in the anterior cerebral artery (ACA) territory (P>0.05). In the middle cerebral artery (MCA) territory, the CBF and CBV increased and TTP decreased in the operated side during CEA; the rCBF and rCBV increased and the rTTP decreased significantly (P<0.05). In 16 patients, CT parameters were improved, SSEP was normal, and MDU was abnormal. In 3 patients, CBF increased by more than 70% during CEA. Relative PCT parameters are sensitive indicators for detecting early cerebral hemodynamic changes during CEA. Cerebral hemodynamics changed significantly in the MCA territory during CEA. CONCLUSIONS Intraoperative PCT could be an important adjuvant monitoring method in CEA. PMID- 27657310 TI - Sexual experience modulates partner preference and mPOA nitric oxide synthase in female rats. AB - Sexually experienced female rats return to the male more quickly after intromissions, exhibit shorter interintromission intervals, and spend more time with the male rat during a test of paced mating behavior in comparison to naive rats. The present study tested whether these changes reflect heightened sexual motivation independent of receipt of vaginocervical stimulation and/or neurochemical changes in the medial preoptic area (mPOA). Ovariectomized, female rats were given estradiol benzoate and progesterone, and then received either 6 paced mating encounters (experienced) or 6 control exposures to an empty paced mating arena (naive). Experienced and naive rats received a no-contact partner preference test under oil vehicle and then under hormone on a different day. Hormonal status and sexual experience led to significantly higher preference for the male. Brains were collected 1 hr after both experienced and naive rats received paced mating to compare mPOA levels of Fos, a marker of neural activity, in response to copulation and nitric oxide synthase (NOS), the enzyme responsible for production of nitric oxide (NO). Expression of NOS was higher in experienced relative to naive rats, whereas Fos was comparable between the groups. The data are consistent with the idea that both sexual motivation and changes to the mPOA contribute to the shift in paced mating behavior induced by sexual experience. (PsycINFO Database Record PMID- 27657309 TI - The role of DeltafosB in the medial preoptic area: Differential effects of mating and cocaine history. AB - The transcription factor deltaFosB (DeltaFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of DeltaFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. DeltaFosB immunoreactivity (ir) was increased in the MPOA of previously naive and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35-37-kDa isoform of DeltaFosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase DeltaFosB ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing DeltaFosB, its dominant negative antagonist DeltaJunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. DeltaFosB overexpression impaired copulation and promoted female-directed aggression, compared to DeltaJunD and control males. These data suggest that DeltaFosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression. (PsycINFO Database Record PMID- 27657311 TI - A Kinetico-Mechanistic Study on CuII Deactivators Employed in Atom Transfer Radical Polymerization. AB - Copper complexes of tertiary amine ligands have emerged as the catalysts of choice in the extensively employed atom transfer radical polymerization (ATRP) protocol. The halide ligand substitution reactions of five-coordinate copper(II) complexes of tris[2-(dimethylamino)ethyl]amine (Me6tren), one of the most active ATRP catalysts, has been studied in a range of organic solvents using stopped flow techniques. The kinetic and activation parameters indicate that substitution reactions on [CuII(Me6tren)X]+ (X- = Cl- and Br-) and [CuII(Me6tren)(Solv)]2+ (Solv = MeCN, DMF, DMSO, MeOH, EtOH) are dissociatively activated; this behavior is independent of the solvent used. Adjusting the effective concentration of the solvent by addition of an olefinic monomer to the solution does not affect the kinetics of the halide binding (kon) but can alter the outer-sphere association equilibrium constant (KOS) between reactants prior to the formal ligand substitution. Halide (X-/Y-) exchange reactions (X = Br and Y = Cl) involving the complex [Cu(Me6tren)X]+ and Y- reveal that the substitution is thermodynamically favored. The influence of solvent on the substitution reactions of [Cu(Me6tren)X]+ is complex; the more polar DMF confers a greater entropic driving force but larger enthalpic demands than MeCN. These substitution reactions are compared with those for copper(II) complexes bearing the tris[2 (diethylamino)ethyl]amine (Et6tren) and tris[2-(pyridyl)methyl]amine (tpa) ligands, which have also been used as catalysts for ATRP. Changing the ligand has a significant impact on the kinetics of X-/Y- exchange. These correlations are discussed in relation to the ability of five-coordinate [CuLX]+ complexes to deactivate radicals in ATRP. PMID- 27657308 TI - Serotonin, estrus, and social context influence c-Fos immunoreactivity in the inferior colliculus. AB - A fundamental task of sensory systems is to extract relevant social information from a range of environmental stimuli in the face of changing behavioral contexts and reproductive states. Neuromodulatory pathways that interact with such contextual variables are 1 mechanism for achieving this. In the mouse inferior colliculus (IC), a midbrain auditory region, the neuromodulator serotonin increases in females interacting with courting males, but events downstream of serotonin release have not been investigated. Here, we manipulated serotonin levels in female mice with the serotonin releaser fenfluramine or the serotonin depleter para-chlorophenylalaninemethyl ester (pCPA). Females were then exposed to an empty cage, a male partner, or a playback of courtship vocalizations, and the numbers of neurons in the IC with positive immunoreactivity for the immediate early gene product c-Fos were measured. The effects of drug treatments depended on social context and estrous state. Fenfluramine had greater effects in the nonsocial than in the partner social treatments. Females in proestrus or estrus and given fenfluramine had higher densities of c-Fos immunoreactive neurons, while females in diestrus had fewer immunoreactive neurons. The drug pCPA had the expected opposite effect of fenfluramine, causing a decreased response in pro/estrus females and an increased response in diestrus females. These findings show that the effects of serotonin on c-Fos activity in the IC of females is dependent on both external context and reproductive state, and suggest that these effects occur downstream of serotonin release. (PsycINFO Database Record PMID- 27657312 TI - Do ENT outpatient computed tomography facilities perceive accreditation as valuable? PMID- 27657313 TI - An unusual cause of tinnitus. PMID- 27657314 TI - Hailey-Hailey disease. PMID- 27657315 TI - Reverse omega technique for single-stage ear lobule reconstruction. PMID- 27657316 TI - Decision making in patients with natural myringostapediopexy: A study of the contralateral ear. AB - Naturally occurring myringostapediopexy frequently results in minimal hearing loss and is asymptomatic. Management decisions in such ears, however, often hinge on an appraisal of evolution toward cholesteatoma. The study of the contralateral ear has been used by our research team to infer the progression of chronic otitis media. This cross-sectional, comparative study describes the clinical findings of the contralateral ear in a series of patients with myringostapediopexy. This study included a historical and current sample of 46 patients divided into a pediatric (<=18 years) and an adult group. Patient distribution according to sex was similar (52.2% male), and 56.5% were adults. Mean conductive hearing loss ranged from 14.1 to 21.2 dB in ears with myringostapediopexy and from 16.0 to 26.6 dB in the contralateral ears according to the frequency assessed. The contralateral ear was normal in only 19.6% of the cases of myringostapediopexy. Central tympanic membrane perforation was found in 6.5% of the cases; perforation retraction, in 17.4%; moderate or severe retraction, in 28.3%; and cholesteatoma, in 28.3%. The prevalence of cholesteatoma in the contralateral ear in the pediatric and adult groups was not significantly different (p = 0.5; chi(2) test). The presence of significant abnormalities, particularly cholesteatoma, in the contralateral ears suggests a probable unfavorable progression in cases of myringostapediopexy and may influence management decisions. PMID- 27657317 TI - Neoplastic causes of nonacute facial paralysis: A review of 221 cases. AB - We conducted a retrospective review to assess the clinical presentation of patients with tumor-related nonacute complete peripheral facial weakness or an incomplete partial facial paresis and to provide an algorithm for the evaluation and management of these patients. Our study population was made up of 221 patients-131 females and 90 males, aged 14 to 79 years (mean: 49.7)-who had been referred to the Facial Nerve Disorders Clinic at our tertiary care academic medical center over a 23-year period with a documented neoplastic cause of facial paralysis. In addition to demographic data, we compiled information on clinical signs and symptoms, radiologic and pathologic findings, and surgical approaches. All patients exhibited gradual-onset facial weakness or facial twitching. Imaging identified an extratemporal tumor in 128 patients (58%), an intratemporal lesion in 55 patients (25%), and an intradural mass in 38 (17%). Almost all of the extratemporal tumors (99%) were malignant, while 91% of the intratemporal and intradural tumors were benign. A transtemporal surgical approach was used in the 93 intratemporal and intradural tumor resections, while the 128 extratemporal lesions required a parotidectomy with partial temporal bone dissection. The vast majority of patients (97%) underwent facial reanimation. We conclude that gradual onset facial paralysis or twitching may occur as a result of a neoplastic invasion of the facial nerve along its course from the cerebellopontine angle to the parotid gland. We caution readers to beware of a diagnosis of "atypical Bell's palsy." PMID- 27657318 TI - Parotid gland metastasis in Merkel cell carcinoma of the head and neck: A series of 14 cases. AB - Merkel cell carcinoma (MCC) is a rare cutaneous cancer of neuroendocrine cell origin that occurs frequently on the head and neck. With a high incidence of local recurrence and regional and distant metastasis, it carries a poor prognosis. We performed a retrospective study to determine the prognostic implications of parotid gland metastasis in MCC of the head and neck. Our study population was made up of 14 patients-13 men and 1 woman, aged 62 to 87 years (mean: 75.9)-who underwent a parotidectomy for the diagnosis of MCC over a period of 10 years and 9 months. Ten patients had a primary skin lesion of the head and neck and 4 presented with a parotid mass and an unknown primary. In all, 13 of the 14 patients were found to have parotid involvement-either a direct extension of MCC into the gland or a positive intraparotid lymph node; some patients had both. All patients underwent tumor excision, and 10 underwent neck dissection. Eleven patients received adjuvant radiotherapy; none received adjuvant chemotherapy. Of the 10 patients who underwent a neck dissection, 6 were found to have a cervical lymph node metastasis on pathologic examination. Follow-up ranged from 1.3 to 39.2 months (mean: 12.4). Three patients were lost to follow-up shortly after surgery, although some information was available on 2 of them. At the final follow-up, mortality data were available on 12 patients; of these, 11 had died. The lone survivor was the patient without a parotid metastasis. Among those known to have died, survival ranged from 1.6 to 49.2 months (mean: 16.0). We conclude that parotid metastasis in patients with MCC of the head and neck is associated with a dismal survival rate that is even worse than the poor survival associated with cervical node involvement. PMID- 27657319 TI - Myeloid sarcomas of the head and neck in pediatric patients with myeloid leukemia. AB - Myeloid sarcoma is a rare extramedullary tumor composed of malignant myeloid cells that occur in the presence of myeloid leukemia. We report a case series of pediatric head and neck myeloid sarcomas representative of the epidemiology, symptomatology, laboratorial correlations, prognoses, and treatment of extramedullary leukemia. Presented are 3 cases involving patients ranging from 17 months to 11 years of age. Two patients were successfully treated with chemotherapy, and in the third patient, a large lytic lesion was treated palliatively with proton beam therapy. Knowledge and recognition of myeloid sarcomas is important as they can be locally invasive, and they may also be used as a diagnostic tool or a prognostic indicator for leukemia. PMID- 27657320 TI - Chronic invasive fungal sinusitis causing a pathologic Le Fort I fracture in an immunocompetent patient. AB - We describe the case of a 77-year-old immunocompetent woman with a history of chronic rhinosinusitis who presented with a pathologic Le Fort I fracture after a forceful sneeze. Imaging revealed diffuse sinus opacification and a Le Fort type I complex fracture involving the maxilla, pterygoid plates, clivus, and right nasal bridge. The patient underwent endoscopic debridement of her sinuses, which revealed mucosal dehiscence and otherwise normal healthy bleeding tissue. Anatomic pathology identified necrotic bone with invasive fungal hyphae. Cultures demonstrated Burkholderia cepacia, diphtheroid organisms, and Enterococcus and Serratia spp. The patient was administered an intravenous antibiotic and antifungal for several months, but interval imaging found no significant improvement in bone healing although the stability of her palate had improved on clinical examination. Chronic rhinosinusitis has been found to be a complication of soft-tissue, orbital, and intracranial infections but, to the best of our knowledge, a pathologic facial fracture secondary to chronic invasive fungal and bacterial rhinosinusitis has not been previously reported in the literature. PMID- 27657321 TI - Primary salivary duct carcinoma arising from the Stensen duct. AB - This report describes a salivary duct carcinoma (SDC) arising from the extraglandular portion of the Stensen duct. The patient was a 56-year-old man who presented with a palpable, elastic, hard mass without tenderness in the right cheek. Computed tomography revealed a tumor of the extraglandular portion of the Stensen duct. Supraomohyoid right neck dissection and total right parotidectomy were performed, and the histologic diagnosis was SDC of the Stensen duct. Postoperatively, the patient received no additional treatment. Neither recurrence nor metastasis was observed during 4 years of follow-up examination. SDC of the Stensen duct is extremely rare. To our knowledge, there is no report that describes primary SDC arising from that location. We also believe this is the first report that describes the clinical course of primary SDC arising from a Stensen duct. PMID- 27657322 TI - Sensorineural hearing loss after otitis media with effusion and subacute mastoiditis after viral infections of the upper respiratory tract: A comparative study of conservative and surgical treatment. AB - Involvement of the middle ear after viral infections of the upper airways may lead to serous otitis media with effusion in the absence of bacterial infection. This can be accompanied by a concomitant shading of the mastoid air cells, which could manifest as a reduced opacity on computed tomography (CT) in the absence of a history of chronic mastoiditis or acute inflammatory signs. This can lead to a subsequent impairment of inner ear function. CT scans reveal an extended pneumatization of the temporal bones in affected patients. Inner ear hearing impairment can probably be attributed to a concomitant labyrinthine reaction-the so-called toxic inner ear lesion. If no remission occurs within 5 days after initial conservative treatment (paracentesis or hemorrheologic infusions), surgical treatment with a mastoidectomy can accelerate hearing restoration. We conducted a retrospective, nonrandomized study of short- and long-term hearing outcomes in patients with a toxic inner ear lesion who had been treated with conservative measures alone (CONS group) or with surgery (SURG group) in a tertiary care referral center. Our study group was made up of 52 consecutively presenting patients (57 ears) who had been seen over a 10-year period; there were 20 patients (21 ears) in the CONS group and 32 patients (36 ears) in the SURG group. Initially, 15 CONS patients (75%) and 18 SURG patients (56%) complained of dizziness or a balance disorder. The initial averaged sensorineural hearing loss (over 0.5, 1.0, 2.0, and 3.0 kHz) was 32.4 +/- 15.6 dB in the CONS group and 35.4 +/- 12.0 dB in the SURG group. At follow-up (mean: 31.7 mo), the SURG group experienced a significantly greater improvement in hearing (p = 0.025). We conclude that patients with viral otitis media and concomitant noninflammatory mastoiditis with impairment of inner ear function (sensorineural hearing loss) experience a better hearing outcome when a mastoidectomy is performed during primary treatment. PMID- 27657323 TI - Isolated epiglottic lymphatic malformation in a 2-year-old: Diagnosis and treatment. AB - Airway obstruction in children has a wide differential diagnosis that includes laryngomalacia, infectious processes, paralysis, extrinsic compression, and other rare anatomic anomalies. Isolated laryngeal lymphatic malformations are rare developments that can manifest with clinically significant airway obstruction. To the best of our knowledge, there have been fewer than 20 reported cases. These laryngeal mucosal lesions are best managed with radiofrequency ablation or laser ablation. We present a case of a 2-year-old child who presented with airway obstruction, initially diagnosed with laryngomalacia, who was subsequently diagnosed and treated for an isolated epiglottic lymphatic malformation. PMID- 27657324 TI - Hemorrhagic polyp with large occult sulcus vocalis in a singer. PMID- 27657325 TI - Endoscopic view of a polyp in a concha bullosa. PMID- 27657326 TI - Onodi cell mucocele: Case report and review of the literature. AB - Onodi cell mucoceles are rare entities that can cause devastating ocular complications if not treated promptly. Delays in the diagnosis are possible because of the wide range of differential diagnoses of unilateral retrobulbar optic neuropathy. We describe a new case of Onodi cell mucocele in a 39-year-old woman, and we present a comprehensive review of the literature on this entity. To the best of our knowledge, no review of Onodi cell mucoceles has been previously published. Our review found that 69% of patients with an Onodi cell mucocele experienced an improvement in vision after surgical decompression. The vast majority of these patients underwent endoscopic decompression; the timing of surgical decompression did not appear to affect outcomes in terms of vision. Onodi cell mucocele requires a high degree of clinical suspicion for diagnosis and a multidisciplinary approach to management that involves primary care physicians, ophthalmologists, and otolaryngologists. Early surgical treatment via an endoscopic approach is recommended for most patients, regardless of the duration of their ophthalmologic signs and symptoms. PMID- 27657327 TI - Impact of nasal septal perforations of varying sizes and locations on the warming function of the nasal cavity: A computational fluid-dynamics analysis of 5 cases. AB - Patients with a nasal septal perforation often exhibit symptoms associated with disturbed airflow, which can have an adverse effect on the warming function of the nasal cavity. The impact of this effect is not fully understood. The warming function is an important factor in the maintenance of nasal physiology. We conducted a study to investigate the impact of septal perforations of various sizes and locations on the warming function during inspiration in 5 patients-3 men and 2 women, aged 25 to 47 years. Three-dimensional computed tomography and computational fluid dynamics were used to model the flux of communication and temperature, and differences among patients were compared. All 5 patients exhibited an impairment of their nasal warming function. As the size of the perforation increased, the flux of communication increased and the warming function decreased. Perforations located in an anterior position were associated with greater damage to the warming function than those in a posterior position. In patients with a large or anteriorly located perforation, airflow temperature in the nasopharynx was decreased. Our findings suggest that septal perforations not only induce airflow disturbance, but they also impair the nasal warming function. Further analysis of warming function is necessary to better explore flow mechanisms in patients with structural abnormalities. PMID- 27657328 TI - Analysis of the Distribution of Energy Barriers in Amorphous Diazepam on the Basis of Computationally Supported NMR Relaxation Data. AB - Crystalline and amorphous diazepam, a psychoactive drug, were investigated by employing spin-lattice relaxation 1H NMR along with atom-atom calculations of the landscape of energy barriers. The activation barriers for reorientation of the methyl group in amorphous diazepam were found to be in the range of 1.9-12.7 kJ/mol. Atom-atom calculations permitted determination of the distribution of energy barriers for reorientations of methyl groups, which was in a good agreement with that obtained on the basis of experimental data. The NMR relaxation combined with calculations provided a quantitative description of the distribution of energy barriers including intra- and inter-molecular interactions. PMID- 27657330 TI - Cu Nanowires with Clean Surfaces: Synthesis and Enhanced Electrocatalytic Activity. AB - Low activity and high cost of electrocatalysts are the major challenge for the commercialization of the direct fuel cells (DFCs) and biofuel cells. In this work, we demonstrate the desirable "clean surfaces" effect of Cu nanocrystals in electrocatalysis. By a new reaction route of Cu2O nanospheres (Cu2O NSs), Cu nanowires (Cu NWs) with high purity and "clean surfaces" are first obtained under mild conditions. Benefiting from the path directing effects and abundant (100) facets, the as-prepared Cu NWs exhibit a lower overpotential to achieve the methanol electro-oxidation reaction (MOR) than that of analogous Cu nanoparticles (Cu NPs). Moreover, the "clean surfaces" provide more available active sites for the efficient transfer of electrons, enabling the Cu NWs to show their enhanced electrocatalytic activity. In the MOR, forward peak current density for the surface-cleaned Cu NWs is 2839 MUA cm-2, which is ca. 6.45-fold higher than that of the Cu NWs with residual capping molecules on their surface. The "clean surfaces" effect can also be extended to the glucose electro-oxidation reaction (GOR), and the enhancement in specific surface area activity for the Cu NWs is 11.3-fold. This work enhances the electrocatalytic performance of Cu nanocrystals without the need for additional noble metals, which opens up new avenues for utilizing non-noble metals in the DFC or biofuel cell applications. PMID- 27657331 TI - Photodetection and Photoswitch Based On Polarized Optical Response of Macroscopically Aligned Carbon Nanotubes. AB - Light polarization is extensively applied in optical detection, industry processing and telecommunication. Although aligned carbon nanotube naturally suppresses the transmittance of light polarized parallel to its axial direction, there is little application regarding the photodetection of carbon nanotube based on this anisotropic interaction with linearly polarized light. Here, we report a photodetection device realized by aligned carbon nanotube. Because of the different absorption behavior of polarized light with respect to polarization angles, such device delivers an explicit response to specific light wavelength regardless of its intensity. Furthermore, combining both experimental and mathematical analysis, we found that the light absorption of different wavelength causes characteristic thermoelectric voltage generation, which makes aligned carbon nanotube promising in optical detection. This work can also be utilized directly in developing new types of photoswitch that features a broad spectrum application from near-ultraviolet to intermediate infrared with easy integration into practical electric devices, for instance, a "wavelength lock". PMID- 27657329 TI - Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3. AB - Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis. PMID- 27657332 TI - Carbaporphyrinoid Systems. AB - Following immediately after the serendipitous discovery of N-confused porphyrins, remarkably diverse carbaporphyrinoid systems have been synthesized and investigated. By replacing a pyrrolic unit within the porphyrin framework with cyclopentadiene, indene, azulene, cycloheptatriene, or benzene, new families of porphyrin-like macrocycles were produced. True carbaporphyrins are fully aromatic structures, while benziporphyrins are essentially devoid of macrocyclic aromatic character, and azuliporphyrins fall midway between the two extremes. Monocarbaporphyrinoids are superior organometallic ligands and form stable complexes with copper(III), silver(III), gold(III), nickel(II), palladium(II), platinum(II), rhodium(III), iridium(III), and ruthenium(II). Unusual oxidation reactions have also been discovered, commonly leading to derivatization of the internal carbon atom. In addition, structural rearrangements have been uncovered that allow the conversion of azuliporphyrins into benzocarbaporphyrins, and benziporphyrins into carbaporphyrins. Although less well studied, many examples of dicarbaporphyrinoids have been reported, and these show equally intriguing characteristics. Furthermore, contracted and expanded carbaporphyrinoids have been investigated. Studies in this area provide fundamental insights into the aromatic properties, tautomerization, and reactivity of porphyrins and related macrocyclic systems. PMID- 27657333 TI - Early Insight Into Neovascular Age-Related Macular Degeneration. PMID- 27657334 TI - Effect of Axial Stretch on Lumen Collapse of Arteries. AB - The stability of the arteries under in vivo pressure and axial tension loads is essential to normal arterial function, and lumen collapse due to buckling can hinder the blood flow. The objective of this study was to develop the lumen buckling equation for nonlinear anisotropic thick-walled arteries to determine the effect of axial tension. The theoretical equation was developed using exponential Fung strain function, and the effects of axial tension and residual stress on the critical buckling pressure were illustrated for porcine coronary arteries. The buckling behavior was also simulated using finite-element analysis. Our results demonstrated that lumen collapse of arteries could occur when the transmural pressure is negative and exceeded a critical value. This value depends upon the axial stretch ratio and material properties of the arterial wall. Axial tensions show a biphasic effect on the critical buckling pressure. The lumen aspect ratio of arteries increases nonlinearly with increasing external pressure beyond the critical value as the lumen collapses. These results enhance our understanding of artery lumen collapse behavior. PMID- 27657335 TI - Dengue Protease Substrate Recognition: Binding of the Prime Side. AB - Dengue virus (DENV), transmitted predominantly in tropical and subtropical regions by the mosquito Aedes aegypti, infects millions of people and leads to dengue fever and thousands of deaths each year. There are no direct-acting antivirals to combat DENV, and molecular and structural knowledge is required to develop such compounds. The dengue NS2B/NS3 protease is a promising target for direct-acting antivirals, as viral polyprotein cleavage during replication is required for the maturation of the viral particle. The NS2B/NS3 protease processes 8 of the 13 viral polyprotein cleavage sites to allow viral maturation. Although these sites share little sequence homology beyond the P1 and P2 positions, most are well conserved among the serotypes. How the other substrate residues, especially at the P' side, affect substrate recognition remains unclear. We exploited the tight-binding general serine protease inhibitor aprotinin to investigate protease-substrate interactions at the molecular level. We engineered aprotinin's binding loop with sequences mimicking the P' side of DENV substrates. P' residues significantly modulate substrate affinity to protease, with inhibition constants varying from nanomolar to sub-millimolar. Structural and dynamic analysis revealed the molecular basis of this modulation and allowed identifying optimal residues for each of the P' positions. In addition, isothermal titration calorimetry showed binding to be solely entropy driven for all constructs. Potential flaviviral P' side inhibitors could benefit from mimicking the optimal residues at P' positions and incorporate hydrophobicity and rigidity to maintain entropic advantage for potency. PMID- 27657336 TI - Renewed interest in the progesterone receptor in breast cancer. PMID- 27657337 TI - Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast cancer cell lines. PMID- 27657338 TI - Impaired T-bet-pSTAT1alpha and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma. PMID- 27657340 TI - Overexpression of connexin 43 reduces melanoma proliferative and metastatic capacity. PMID- 27657339 TI - Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein alpha-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease due to the lack of specific early diagnostic markers. To improve the outcomes, proteomic approaches are being developed for the discovery of novel biomarkers of PDAC. METHODS: Using tandem mass tag labelling and LC-MS/MS, we performed comparative analyses of pre- and postoperative sera from PDAC patients to identify specific serum biomarkers for PDAC. In validation studies, we evaluated the discriminatory power of candidate proteins. RESULTS: Among the 302 proteins analysed, 20 were identified as potential biomarkers, with C4b-binding protein alpha-chain (C4BPA) and polymeric immunoglobulin receptor (PIGR) being selected for further analysis. The sera levels of C4BPA and PIGR were significantly higher in the preoperative PDAC patients than in the postoperative ones (P<0.008, P<0.036, respectively). In addition, serum C4BPA levels, but not PIGR, in patients with PDAC were significantly higher than those in healthy controls as well as in patients with pancreatitis and other malignancies including biliary tract cancers (BTC) (P<0.001). The respective area under the receiver operator characteristics (ROC) curve (AUC) was 0.860 for C4BPA, 0.846 for CA19-9 and 0.930 for the combination of C4BPA and CA19-9 in PDAC vs non-cancer individuals. The respective AUC was 0.912 for C4BPA, 0.737 for CA19-9 in Stages I and II of PDAC, 0.854 for C4BPA and 0.264 for CA19-9 in PDAC vs BTC. CONCLUSIONS: We have demonstrated that C4BPA is a novel serum biomarker for detecting early stage PDAC, as well as for distinguishing PDAC from other gastroenterological cancers. Further analysis in large cohort studies will warrant C4BPA as a promising biomarker of PDAC in clinical use. PMID- 27657342 TI - Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer. PMID- 27657343 TI - Error-Safe, Portable, and Efficient Evolutionary Algorithms Implementation with High Scalability. AB - We present an efficient massively parallel implementation of genetic algorithms for chemical and materials science problems, solely based on Java virtual machine (JVM) technologies and standard networking protocols. The lack of complicated dependencies allows for a highly portable solution exploiting strongly heterogeneous components within a single computational context. At runtime, our implementation is almost completely immune to hardware failure, and additional computational resources can be added or subtracted dynamically, if needed. With extensive testing, we show that despite all these benefits, parallel scalability is excellent. PMID- 27657341 TI - The combined endocrine receptor in breast cancer, a novel approach to traditional hormone receptor interpretation and a better discriminator of outcome than ER and PR alone. AB - BACKGROUND: The functional role of progesterone receptor (PR) signalling was previously unclear and PR testing in breast cancer is controversial. Recent defining work has highlighted the functional crosstalk that exists between the oestrogen receptor (ER) and PR. The purpose of this retrospective cohort study was to compare the prognostic value of the combined ER and PR score with either ER or PR alone. METHODS: Tumour Allred ER and PR scores were reclassified as negative, low and high. The combined endocrine receptor (CER) was calculated as the average of the reclassified ER and PR scores, resulting in three groups: CER negative, impaired and high. Cox proportional hazards models were used to estimate disease-free survival (DFS) and breast cancer-specific survival (BCSS). RESULTS: The CER was a more powerful predictor of 5-year DFS and BCSS than either ER or PR alone. In multivariate analysis that included ER, PR and CER, only CER remained an independent prognostic variable for 5-year DFS (hazard ratio (HR) 0.393; CI: 0.283-0.548, P=0.00001) and BCSS (HR 0.553; CI: 0.423-0.722; P=2.506 * 10-8). In ER-positive (ER+) patients impaired CER was an independent marker of poor outcome for 5-year DFS (HR 2.469; CI: 1.049-5.810; P=0.038) and BCSS (HR 1.946; CI: 1.054-3.596; P=0.033) in multivariate analysis that included grade, lymph node, tumour size, HER2 status and PR status. The results were validated in a separate cohort of patients. CONCLUSIONS: Combined endocrine receptor is a more powerful discriminator of patient outcome than either ER or PR alone. Economical and simple, it can identify risk in ER+ early breast cancer and potentially be used for adjuvant cytotoxic chemotherapy decision-making. PMID- 27657344 TI - Preserving Neurocognition in Patients With Brain Metastases. PMID- 27657345 TI - Subinternship in Radiology - A Practical Start to the Specialization? AB - Purpose: To identify factors influencing medical students to choose radiology in the four-month clinical elective in the final year of medical school following radiology subinternships. Materials and Methods: A subsample of medical students in a nationwide German online survey evaluated a subinternship in radiology (19 items). They were divided into four groups: Students who could imagine doing a clinical elective in radiology in the practical year based on their experiences during the subinternship ("yes, based on subinternship"), students who could not ("no, based on subinternship") and students who had made this decision prior to the subinternship ("yes, prior to subinternship" and "no, prior to subinternship"). Results: 94 medical students evaluated a radiology subinternship (54.4 % females). Based on their experiences during the subinternship, 54 students (57.4 %) intended to do a final year clinical elective in radiology, 39 of them (41.5 %) being encouraged by the subinternship. 40 (42.6 %) reported having a negative attitude towards a clinical elective in radiology, 16 of them (17.0 %) having made this decision based on their subinternship experience. Groups did not differ regarding gender (p = 0.396) and age (p = 0.853). Students motivated to do a final year clinical elective in radiology experienced excellent academic teaching (p = 0.001) and practical involvement (p = 0.003), achieved their learning goals more often (p = 0.001), were better integrated into the team (p = 0.001), and acquired more practical skills (p = 0.003). Overall satisfaction was higher in these groups (p = 0.001). Conclusion: Satisfaction with a radiology subinternship is crucial for motivating medical students to do a final year clinical elective in radiology. A structured subinternship and continuous mentoring should be targeted to keep students connected to radiology. Key Points: * Radiology subinternships influence further interest in the specialization.* The quality and structure of teaching critically influence student satisfaction.* Team integration and practical involvement positively affect the attitude towards a specialization. Citation Format: * Kasch R, Wirkner J, Hosten N et al. Subinternship in Radiology - A Practical Start to the Specialization? Fortschr Rontgenstr 2016; 188: 1024 - 1030. PMID- 27657347 TI - Asymmetric Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride. AB - The asymmetric (er > 99:1) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The Sharpless asymmetric dihydroxylation is the key asymmetric transformation used in the synthesis of this intermediate. It is carried out on an olefin that is accessed in three steps from commercially available materials, making the overall synthetic sequence very concise. The common diol intermediate derived from the Sharpless asymmetric dihydroxylation is converted into either a trans- or cis-epoxide, and these are subsequently converted to (+)-anti- and (-)-syn-mefloquine, respectively. X-ray crystallographic analysis of derivatives of (+)-anti- and (-)-syn-mefloquine is used to lay to rest a 40 year argument regarding the absolute stereochemistry of the mefloquines. A formal asymmetric (er > 99:1) synthesis of (+)-anti-mefloquine hydrochloride is also presented that uses a Sharpless asymmetric epoxidation as a key step. PMID- 27657349 TI - Predictors for Development of Pressure Ulcer in End-of-Life Care: A National Quality Register Study. AB - BACKGROUND: The scientific knowledge about pressure ulcers (PUs) is growing, but there is a shortage of studies of PUs at end of life. The recommendations regarding PU prevention in palliative care (PC) are based on consensus documents. AIM: To use data from a national register to identify predictors for development of PUs at the end of life. DESIGN: A retrospective, descriptive, and comparative study design was used. SETTING/PARTICIPANTS: All deceased patients over 17 years old (n = 60,319) and registered in the Swedish Register of Palliative Care (SRPC) during 2014 were included. STATISTICAL ANALYSIS: Logistic regression. RESULTS: In the full model, all health units except general palliative home care had a significantly higher incidence of PUs than did the nursing homes. The well-known predictors of PUs in general, diabetes, postfracture state, infections, and multiple sicknesses, are predictors even in dying patients. Dementia was significantly associated with lower likelihood of PUs, while pain was associated with more PUs. Intravenous drip or enteral feeding was associated with a significantly decreased likelihood of developing PUs. CONCLUSIONS: The SRPC could be a unique resource for quality improvement and research. The present study cannot prove causation, but it can report correlations between background variables and PU prevalence. More studies, with different designs, are warranted to establish the roles of risk factors for PU in end-of-life care. PMID- 27657348 TI - Serologic response to porcine circovirus type 1 (PCV1) in infants vaccinated with the human rotavirus vaccine, RotarixTM: A retrospective laboratory analysis. AB - In 2010, porcine circovirus type 1 (PCV1) material was unexpectedly detected in the oral live-attenuated human rotavirus (RV) vaccine, RotarixTM (GSK Vaccines, Belgium). An initial study (NCT01511133) found no immunologic response against PCV1 in 40 vaccinated infants. As a follow-up, the current study (NCT02153333), searched for evidence of post-vaccination serologic response to PCV1 in a larger number of archived serum samples. Unlike the previous study, serum anti-PCV1 antibodies were assessed with an adapted Immuno Peroxidase Monolayer Assay (IPMA) using a Vero-adapted PCV1 strain. Samples from 596 infants who participated in clinical trials of the human RV vaccine were randomly selected and analyzed. The observed anti-PCV1 antibody seropositivity rate 1-2 months post-dose 2 was approximately 1% [90% Confidence Interval (CI): 0.3-2.6] (3/299 samples) in infants who received the human RV vaccine and 0.3% [90% CI: 0.0-1.6] (1/297 samples) in those who received placebo; the difference between the groups was 0.66 [90% CI: -2.16-0.60]. One subject in the vaccinated group was also seropositive before vaccination. Notably, the seropositivity rate observed in vaccinated subjects was below that observed during assay qualification in samples from unvaccinated subjects outside of this study (2.5%; 5/200 samples). No serious adverse events had been reported in any of the 4 subjects providing anti PCV1 positive samples during the 31-day post-vaccination follow-up period in the original studies. In conclusion, the presence of PCV1 in the human RV vaccine is considered to be a manufacturing quality issue and does not appear to pose a safety risk to vaccinated infants. PMID- 27657350 TI - Magnetic field therapy in patients with cytostatics-induced polyneuropathy: A prospective randomized placebo-controlled phase-III study. AB - No causal treatment for chemotherapy-induced peripheral neuropathy (CIPN) is known. Therefore, there is an urgent need to develop a therapy for CIPN. Only scarce clinical data are available concerning magnetic field therapy (MFT) in this context. We conducted a unicentric, randomized, double-blind, placebo controlled phase-III trial of an MFT device versus placebo. In this study, we randomized 44 patients with CIPN to two treatment groups, where 21 patients were treated with MFT (Group 1) and 23 patients received placebo (Group 2). We evaluated the efficacy of MFT at baseline (T1 ), after 3 weeks of study treatment (T2 ), and after 3 months of study treatment (T3 ). The primary endpoint was nerve conduction velocity (NCV), while secondary endpoints were the Common Toxicity Criteria (CTCAE) score and the Pain Detect End Score at T3 . Seventeen of the patients in Group 1 and 14 patients in Group 2 completed the respective study treatment. The primary endpoint, significant improvement of NCV at T3 , was achieved by MFT (P = 0.015), particularly for sensory neurotoxicity of the peroneal nerve. Also, in respect to the secondary endpoints, significant improvement (P = 0.04) was achieved in terms of the patients' subjectively perceived neurotoxicity (CTCAE score), but not of neuropathic pain (P = 0.11). From data in the randomized study presented here, a positive effect on the reduction of neurotoxicity can be assumed for the MFT device. Patients with sensory neurotoxicity in the lower limbs, especially, should therefore be offered this therapy. Bioelectromagnetics. 38:85-94, 2017. (c) 2016 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc. PMID- 27657351 TI - Effect of a social intervention of choice vs. control on depressive symptoms, melancholy, feeling of loneliness, and perceived togetherness in older Finnish people: a randomized controlled trial. AB - OBJECTIVES: This study examined effects of a social intervention on depressive symptoms, melancholy, loneliness, and perceived togetherness in community dwelling Finnish older people. METHOD: Promotion of mental well-being in older people (GoodMood; ISRCTN78426775) was a single-blinded randomized control trial lasting 1.5 years. Two hundred and twenty-three persons aged 75-79 years reporting symptoms of loneliness or melancholy were randomized into intervention and control groups. The intervention group was allowed to choose among supervised exercise, social activity, or personal counseling. Follow-up measurements were conducted at the end of 6-month intervention, and at 3, 6, and 12 months post intervention. RESULTS: Number of depressive symptoms remained unchanged, while loneliness and melancholy decreased in both the intervention and control groups during the study (p < 0.001). Social integration increased in the intervention group but not in controls (p = 0.041). Attachment and guidance increased in both groups (p < 0.001). CONCLUSION: The intervention did not alleviate depressed mood. Positive changes over time were observed in loneliness, feelings of melancholy, attachment, and guidance but these occurred independently of the intervention. Our secondary analysis suggests that the intervention increased perceived social integration. In sum, the effects of the intervention were moderate only and did not expedite further overcoming depressive mood or loneliness. PMID- 27657352 TI - Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand. AB - It is well established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor excitability of the left non-trained hand. Subjects practiced a visuomotor tracking task engaging right digit V for 6 weeks with either progressively increasing task difficulty (PT) or no progression (NPT). Corticospinal excitability (CSE) was evaluated from the resting motor threshold (rMT) and recruitment curve parameters following application of transcranial magnetic stimulation (TMS) to the ipsilateral primary motor cortex (iM1) hotspot of the left abductor digiti minimi muscle (ADM). PT led to significant improvements in left-hand motor performance immediately after 6 weeks of training (63 +/- 18%, P < 0.001) and 8 days later (76 +/- 14%, P < 0.001). In addition, PT led to better task performance compared to NPT (19 +/- 15%, P = 0.024 and 27 +/- 15%, P = 0.016). Following the initial training session, CSE increased across all subjects. After 6 weeks of training and 8 days later, only PT was accompanied by increased CSE demonstrated by a left and upwards shift in the recruitment curves, e.g. indicated by increased MEPmax (P = 0.012). Eight days after training similar effects were observed, but 14 months later motor performance and CSE were similar between groups. We suggest that progressively adjusting demands for timing and accuracy to individual proficiency promotes motor skill learning and drives the iM1-CSE resulting in enhanced performance of the non-trained hand. The results underline the importance of increasing task difficulty progressively and individually in skill learning and rehabilitation training. PMID- 27657354 TI - Use of internal jugular vein grafts in reconstructing multiple venous orifices of right hepatic grafts without the middle hepatic vein trunk. PMID- 27657353 TI - Association between access to accelerated partial breast irradiation and use of adjuvant radiotherapy. AB - BACKGROUND: The current study was performed to determine whether access to facilities performing accelerated partial breast irradiation (APBI) is associated with differences in the use of adjuvant radiotherapy (RT). METHODS: Using the National Cancer Data Base, the authors performed a retrospective study of women aged >=50 years who were diagnosed with early-stage breast cancer between 2004 and 2013 and treated with breast-conserving surgery (BCS). Facilities performing APBI in >=10% of their eligible patients within a given year were defined as APBI facilities whereas those not performing APBI were defined as non-APBI facilities. All other facilities were excluded. The authors identified independent factors associated with RT use using multivariable logistic regression with clustering in the overall sample as well as in subsets of patients with standard-risk invasive cancer, low-risk invasive cancer, and ductal carcinoma in situ. RESULTS: Among 222,544 patients, 76.6% underwent BCS plus RT and 23.4% underwent BCS alone. The likelihood of RT receipt in the overall sample did not appear to differ significantly between APBI and non-APBI facilities (adjusted odds ratio [AOR], 1.02; P = .61). Subgroup multivariable analysis demonstrated that among patients with standard-risk invasive cancer, there was no association between evaluation at an APBI facility and receipt of RT (AOR, 0.98; P = .69). However, patients with low-risk invasive cancer were found to be significantly more likely to receive RT (54.4% vs 59.5%; AOR, 1.22 [P<.001]), whereas patients with ductal carcinoma in situ were less likely to receive RT (56.9% vs 55.3%; AOR, 0.89 [P = .04]) at APBI facilities. CONCLUSIONS: Patients who were eligible for observation were more likely to receive RT in APBI facilities but no difference was observed among patients with standard-risk invasive cancer who would most benefit from RT. Cancer 2017;123:502-511. (c) 2016 American Cancer Society. PMID- 27657356 TI - Differences in Perceptions Among Radiologists, Referring Physicians, and Patients Regarding Language for Incidental Findings Reporting. AB - OBJECTIVE: The purpose of this article is to compare radiologists', referring physicians', and patients' interpretations of expressions within radiology reports to describe findings of likely low clinical significance. SUBJECTS AND METHODS: Surveys were completed by abdominal radiologists (n = 13), physicians referring patients for abdominal CT (n = 59), and outpatients awaiting imaging (n = 51) at a large urban academic medical center. Surveys presented 10 expressions for describing an incidental 5-mm liver lesion and asked respondents to select from a list of choices their perceived likelihood that the lesion represented malignancy. Radiologists and referrers were asked supplemental questions. RESULTS: Compared with radiologists' concern, referrers' and patients' concerns were higher for four and seven of the 10 expressions. Only the expression "benign cyst" was associated with no concern in all groups; "most likely a cyst" and "too small to characterize" were associated with median levels of concern of 0% for radiologists, > 0% to 1% for referrers, and > 2% to 5% for patients. Expressions containing the phrase "not excluded" had the highest concern in all groups. Referrers' likelihood of ordering follow-up imaging varied widely for the expressions (e.g., "benign cyst," 2%; "cyst," 22%; "most likely a cyst," 46%; "most likely a cyst, although tumor not excluded," 75%). Overall, the preferred phrase for a 5-mm liver lesion with benign features in normal-risk patients was "cyst" among radiologists and "benign cyst" among referrers. Seventy-six percent of referring physicians thought that radiology reports should indicate whether follow-up imaging is recommended for such lesions. CONCLUSION: Ambiguity in radiologists' language for incidental low-risk findings may contribute to increased patient anxiety and follow-up testing, warranting greater radiologist attention and potentially new practice or reporting strategies. PMID- 27657357 TI - Identification of growing bacteria during litter decomposition in freshwater through H218O quantitative stable isotope probing. AB - Identification of microorganisms that facilitate the cycling of nutrients in freshwater is paramount to understanding how these ecosystems function. Here, we identify growing aquatic bacteria using H218O quantitative stable isotope probing. During 8 day incubations in 97 atom % H218O, 54% of the taxa grew. The most abundant phyla among growing taxa were Proteobacteria (45%), Bacteroidetes (30%) and Firmicutes (10%). Taxa differed in isotopic enrichment, reflecting variation in DNA replication of bacterial populations. At the class level, the highest atom fraction excess was observed for OPB41 and delta-Proteobacteria. There was no linear relationship between 18 O incorporation and abundance of taxa. delta-Proteobacteria and OPB41 were not abundant, yet the DNA of both taxa was highly enriched in 18 O. Bacteriodetes, in contrast, were abundant but not highly enriched. Our study shows that a large proportion of the bacterial taxa found on decomposing leaf litter grew slowly, and several low abundance taxa were highly enriched. These findings indicating that rare organisms may be important for the decomposition of leaf litter in streams, and that quantitative stable isotope probing with H218O can be used to advance our understanding of microorganisms in freshwater by identifying species that are growing in complex communities. PMID- 27657358 TI - Circulating lymphoma cells in intravascular large B-cell lymphoma. PMID- 27657355 TI - The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases. AB - Most of what is known about fungi in the human vagina has come from culture-based studies and phenotypic characterization of single organisms. Though valuable, these approaches have masked the complexity of fungal communities within the vagina. The vaginal mycobiome has become an emerging field of study as genomics tools are increasingly employed and we begin to appreciate the role these fungal communities play in human health and disease. Though vastly outnumbered by its bacterial counterparts, fungi are important constituents of the vaginal ecosystem in many healthy women. Candida albicans, an opportunistic fungal pathogen, colonizes 20% of women without causing any overt symptoms, yet it is one of the leading causes of infectious vaginitis. Understanding its mechanisms of commensalism and patho-genesis are both essential to developing more effective therapies. Describing the interactions between Candida, bacteria (such as Lactobacillus spp.) and other fungi in the vagina is funda-mental to our characterization of the vaginal mycobiome. PMID- 27657359 TI - A Nano-Biosensor for the Detection of 185delAG Mutation in BRCA1 Gene, Leading to Breast Cancer. AB - A method was developed for the detection of 185delAG mutation in BRCA1 gene, which is responsible for 85% and 63% lifetime risks of hereditary breast and ovarian cancer in women, respectively. The protocol is based on the quenching and recovering fluorescence emission of fluorescein-based dye (FAM)-labeled DNA in the presence of graphene oxide (GO), followed by addition of cDNA or mDNA. In addition, ligase reaction between a DNA probe attached to GO and a DNA possessing FAM on 5' terminal in the presence of cDNA or mDNA was applied. PMID- 27657360 TI - Why routine prophylactic use of vancomycin should be recommended against: response. PMID- 27657361 TI - The Role of Report Comparison, Analysis, and Discrepancy Categorization in Resident Education. AB - OBJECTIVE: The purpose of this study was to show the value of automated radiology report comparison and analysis in resident education by providing qualitative and quantitative feedback on the discrepancies between preliminary and finalized reports. MATERIALS AND METHODS: Anonymous surveys on dictation practices and the process of reviewing reports were completed by consenting radiology residents and faculty. All 277 reports obtained across all modalities during the 4-week study were retrieved from the dictation server in both their preliminary and finalized states, for a total of 544 reports. Disparities between these reports were automatically compared side by side and were categorized according to clinical relevance, report quality, or report structure. The frequency of report corrections was compared between junior (postgraduate years [PGYs] 2 and 3) and senior (PGYs 4 and 5) residents. Residents were surveyed regarding the usefulness of the feedback. RESULTS: Eighty-six reports (31%) were verified as unchanged, with no statistically significant difference noted between junior and senior residents (33.2% and 25.9%, respectively; p = 0.03). Of the 370 discrepancies noted in the 191 edited reports, 81 (21.9%) were discrepancies in clinically relevant findings; 106 (28.6%) were discrepancies in report quality; and 183 (49.5%) were discrepancies in report structure, syntax, or both. Although senior residents had a lower rate of discrepancies in the clinical relevance category than did junior residents (12.8% and 26.5%; p = 0.004), they had a higher rate of discrepancies in the report quality category (58.4% and 44.9%; p = 0.02). Surveys of both residents and faculty showed strong support for the project. CONCLUSION: Categorization of corrections was deemed useful by residents and can be helpful in assessing elements of reporting accuracy for individual feedback. Quantitative report comparison and analysis show promise in tailoring resident education at the programmatic level as cumulative data are gathered and trends are analyzed. PMID- 27657362 TI - Expression of EGF, EGFR, and proliferation in placentas from pregnancies complicated with preeclampsia. AB - OBJECTIVE: To investigate proliferation, EGF and EGFR expression of villous trophoblast (VTB), decidual cells (DC), and extravillous trophoblast (EVTB) in the placentas from pregnancies complicated with preeclampsia (PE) and to compare them with placentas from normal pregnancies. METHODS: Twenty-nine PE placentas and 19 control placentas were studied for EGF and EGFR immunohistochemical expression (noted as week, moderate or strong). Proliferation was expressed as the proliferation index. The CK7 antibody was used to distinguish DC from EVTB. RESULTS: DC and EVTB proliferation was significantly higher in PE placentas. EGFR and EGF expression showed no significant difference. CONCLUSION: Higher DC and EVTB proliferation in PE could contribute to PE development. PMID- 27657363 TI - Analyzing pedestrian crash injury severity under different weather conditions. AB - OBJECTIVE: Pedestrians are the most vulnerable road users due to the lack of mass, speed, and protection compared to other types of road users. Adverse weather conditions may reduce road friction and visibility and thus increase crash risk. There is limited evidence and considerable discrepancy with regard to impacts of weather conditions on injury severity in the literature. This article investigated factors affecting pedestrian injury severity level under different weather conditions based on a publicly available accident database in Great Britain. METHOD: Accident data from Great Britain that are publicly available through the STATS19 database were analyzed. Factors associated with pedestrian, driver, and environment were investigated using a novel approach that combines a classification and regression tree with random forest approach. RESULTS: Significant severity predictors under fine weather conditions from the models included speed limits, pedestrian age, light conditions, and vehicle maneuver. Under adverse weather conditions, the significant predictors were pedestrian age, vehicle maneuver, and speed limit. CONCLUSIONS: Elderly pedestrians are associated with higher pedestrian injury severities. Higher speed limits increase pedestrian injury severity. Based on the research findings, recommendations are provided to improve pedestrian safety. PMID- 27657364 TI - Clinical, Morphologic, and Pathologic Features Associated With Increased FDG Uptake in Schwannoma. AB - OBJECTIVE: The objective of this study was to investigate the clinical, morphologic, and pathologic features associated with increased 18F-FDG uptake in benign schwannomas. MATERIALS AND METHODS: Twenty-two schwannomas in 22 patients (age range, 25-81 years) who had FDG PET or PET/CT scans and subsequently underwent surgical re-section were retrospectively analyzed. The maximum standardized uptake value (SUVmax) was compared with patient age, sex, tumor location (gastrointestinal vs nongastrointestinal origin), tumor size, gross appearance, intratumoral cellularity, intratumoral infiltration of inflammatory cells, presence of peritumoral lymphoid cuffs, and expression status of glucose transporters 1 and 3 on tumor cells. RESULTS: The SUVmax of schwannomas ranged from 1.5 to 17.3 (median, 3.7). Significantly higher SUVmax was observed in gastrointestinal schwannomas (n = 4) compared with nongastrointestinal schwannomas (n = 18, p = 0.007) and in schwannomas with peritumoral lymphoid cuffs (n = 5) compared with those without peritumoral lymphoid cuffs (n = 17, p = 0.001). A significant correlation was seen between tumor location and the presence of peritumoral lymphoid cuffs (p < 0.001). Age, sex, tumor size, gross appearance, intratumoral cellularity, intratumoral inflammatory cell infiltration, and expression status of glucose transporters 1 and 3 on tumor cells had no significant correlation with SUVmax. CONCLUSION: Gastrointestinal schwannomas and schwannomas with peritumoral lymphoid cuffs may be associated with elevated FDG uptake. Knowledge of the features of schwannomas associated with increased uptake may be helpful to avoid misinterpretation of benign schwannomas as malignancy. PMID- 27657365 TI - Developing Collections With Get It Now: A Pilot Project for a Hybrid Collection. AB - As health sciences libraries transition from print to online journal collections that require significant institutional funding, librarians are investigating the use of on demand services in order to meet customer need and contain costs. In 2014 a three-year pilot project to determine if unmediated access to the Copyright Clearance Center's Get It Now service would expand access to needed content and provide usage data to inform collections decision making. The service provides rapid, automated delivery of unsubscribed, high-quality journal articles directly to the customer. The three-year pilot project aims to compare the cost of Get It Now to the traditional subscription model to learn if the service is a cost-effective and sustainable alternative that improves customer satisfaction and that can transform collection development with a hybrid model for journal acquisitions. PMID- 27657366 TI - Low-Tech Scavenger Hunt Model for Student Orientation. AB - Scavenger hunts are an effective, fun way of orienting new students to the library. The low-tech nature and small scale of the scavenger hunt program described here might be more suitable for health sciences libraries than other models, particularly for libraries with small staffs. This model also includes a unique optional element useful for library marketing. This article describes the methods used, shares reactions of program participants, and provides suggestions for those considering orienting students in this way. PMID- 27657367 TI - An Embedded Librarian Program: Eight Years On. AB - This article examines an embedded librarian program eight years after implementation in a large academic health center. Librarians were physically moved into the colleges of pharmacy, public health, and nursing. Statistics are reported as well as comments from the participating librarians and faculty members. Strong relationships have been built between librarians, faculty members, and students. Locating the librarians among faculty and students led to a better understanding of client needs and an increased awareness of librarian competencies and services resulting in partnerships and greater utilization of library services. PMID- 27657368 TI - AAHSL Twitter Use From 2007 to 2014: An Exploratory Analysis. AB - Twitter is a popular social media platform used by organizations for communication and marketing purposes. Many libraries, including members of the Association of Academic Health Sciences Libraries (AAHSL), have Twitter accounts, but how do these libraries use Twitter to communicate with their constituents and are they using it effectively? This study is a large-scale observational study of Twitter use within AAHSL libraries and reflects on the usage patterns present in the context of social media best practices. This study also aims to expand upon best practices for implementing and maintaining a Twitter account in a health sciences library setting. PMID- 27657369 TI - Emerging Roles for Librarians in the Medical School Curriculum and the Impact on Professional Identity. AB - This article discusses the impact on professional identity for health sciences librarians participating in the curriculum revision and development process. A qualitative survey, designed to examine the current roles, values, and self identification of health sciences librarians involved in curricular revision, was conducted. The respondents discussed how they had participated in the planning, implementation, and rollout phases of revised curricula. They identified skills and values essential to successful participation and described the impact of expanded professional relationships on new identities as educators, change agents, and problem solvers. The study may add to the knowledge base of skills and attitudes needed for successful practice in these newly emerging roles. PMID- 27657370 TI - AMED: The Allied and Complementary Medicine Database. AB - AMED: The Allied and Complementary Medicine Database is a resource from the Health Care Information Service of the British Library. AMED offers access to complementary and alternative medicine topics, such as acupuncture, chiropractic, herbalism, homeopathy, hospice care, hypnosis, palliative care, physiotherapy, podiatry, and rehabilitation. This column features a sample search to demonstrate the type of information available within AMED. AMED is available through the EBSCOhost and OVID platforms. PMID- 27657371 TI - Online Professional Profiles: Health Care and Library Researchers Show Off Their Work. AB - In an increasingly digital world, online profiles can help health care and library professionals showcase their research and scholarly work. By sharing information about their investigations, studies, and projects, health care and library researchers can elevate their personal brand and connect with like-minded individuals. This column explores different types of online professional profiles and addresses some of the concerns that come with using them. A list of online professional profile and platform examples is also provided. PMID- 27657372 TI - Meeting Nontraditional Medical Information Needs for the Unique Populations and Geographically Remote Locations of Alaska. AB - The types of information required by hospital and clinical staff can be greatly influenced by the geography and culture of the area in which they operate. In some situations, information must be acquired from sources that fall outside the traditional provisions of a medical or reference library. This article provides examples of the unique information needs of clinical staff serving a primarily Native Alaskan and Native American clientele in Alaska. It also presents sources and personnel utilized to meet those information needs outside of traditional reference sources. PMID- 27657373 TI - Tips for the First-Year Health Sciences Librarian. AB - A new librarian offers advice and insights about what she has learned from working at a library within a health science center. The librarian earned her MLIS in spring 2015, and while she had previous teaching experience, she realized there was much more learning needed to properly teach medical, graduate and allied health students, faculty, and residents. In this "one-year on the job" column, the librarian describes the different teaching experiences today's librarians encounter, and reflects on what she has learned from them and how they shape her view of the profession. PMID- 27657375 TI - Understanding Mental Disorders: Your Guide to DSM-5, by the American Psychiatric Association. PMID- 27657376 TI - Repositioning Reference: New Methods and New Services for a New Age, by Laura Saunders, Lillian Rozaklis, and Eileen G. Abels. PMID- 27657377 TI - Linked Data for Libraries, Archives and Museums: How to Clean, Link and Publish Your Metadata, by Seth Van Hooland and Ruben Verbough. PMID- 27657378 TI - Consumer Health Information Services and Programs: Best Practices, edited by M. Sandra Wood. PMID- 27657381 TI - Tokenism costs nothing. AB - It is not often that I find myself agreeing with the NHS Chief Executive but at last week's 'Strategy for nursing' conference his criticisms of health service management were well placed. According to Duncan Nichol, managers continue to pay lip service to recruitment and retention issues. He claimed there was no real commitment to initiatives such as flexible working hours and creche facilities and he accused employers of tokenism. PMID- 27657382 TI - Wound cleansing - which solution? AB - It is an instinctive reaction in both humans and animals to lick a wound. This is the most natural method of wound cleansing and is comforting, providing some temporary pain relief, perhaps by triggering the release of endorphins. A review of written records of wound care dating back 4,000 years suggests that humans have used many other methods ( 1 ). PMID- 27657383 TI - Nursing's need for a voice in post-reform NHS. AB - National Health Service management chief Duncan Nichol last week pledged to help nurses have a top-level say in running post-reform NHS units. PMID- 27657380 TI - The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines. AB - We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou-Talalay method, and cell viability and clonogenicity were also evaluated. Apoptosis, reactive oxygen species (ROS) levels, and cell cycle distribution were determined by flow cytometry. ER stress, caspase activation, and the AKT, MAPK/ERK, and STAT-3 pathways were analyzed by Western blot. Combination treatment with romidepsin and lenalidomide had a synergistic effect in Hut-78 cells and an additive effect in Karpas-299 cells at 24 hours and did not decrease the viability of normal peripheral blood mononuclear cells. This drug combination induced apoptosis, increased ROS production, and activated caspase-8, -9, -3 and PARP. Apoptosis was associated with increased hallmarks of ER stress and activation of UPR sensors and was mediated by dephosphorylation of the AKT, MAPK/ERK, and STAT3 pathways.The combination of romidepsin and lenalidomide shows promise as a possible treatment for T-cell lymphoma. This work provides a basis for further studies. PMID- 27657385 TI - NVQ leads to rows over future pay structure. AB - Angry controversy over Whitley-busting pay and underfunding greeted the launch of the new support workers' qualification in London last week. PMID- 27657384 TI - ? AB - Fighting Spirit. World War II nurse and author Brenda McBryde pictured at last week's Royal College of Nursing History of Nursing Society conference on the Battle of Britain, which highlighted the role of nurses. PMID- 27657386 TI - ? AB - Jennette Golding, the Royal College of Nursing's Special Advisor to the General Secretary , is to join Nursing Standard's editorial advisory board. PMID- 27657387 TI - UKCC must get tough over conduct. AB - The United Kingdom Central Council is too nice to people who are are guilty of misconduct but not struck off the professional register, the English National Board's investigation committee believes. PMID- 27657388 TI - Demand for extra nurses outstrips availability. AB - An increase in numbers of nurses employed by the health service is not , keeping pace with growth in demand, a health authorities report highlighting an L806 million National Health Service funding shortfall warns. PMID- 27657390 TI - ? AB - First World War veterans Donald Hodge and Andy Andrews met for the first time since 1916 at a Royal College of Nursing reception in London last week. PMID- 27657389 TI - Flexibility for course recognition. AB - Schools of nursing offering ENB approved courses will be able to be more flexible in the way they recognise previous study undertaken by nurses following the recommendations in a new ENB report. PMID- 27657391 TI - Midwife 'couldn't afford to work on bank'. AB - A midwife who was asked to work ten shifts without pay before being allowed onto the bank at Carlisle Hospital turned it down because she couldn't afford to pay for her fares or child care, it was revealed last week. PMID- 27657393 TI - Managers urged to care more for their staff. AB - National Health Service staffing problems will never be solved unless management philosophy radically changes co enable nurses to cherish their work, RCN Policy and Research Director Derek Dean warned. PMID- 27657392 TI - Project 2000 faces underfunding. AB - The English National Board has warned that some aspects of Project 2000 have been underfunded despite assurances of full-funding from the Department of Health. PMID- 27657394 TI - ? AB - Keynote speaker Duncan Nichol. PMID- 27657396 TI - Education must end its isolationism. AB - Nursing education must drop its isolationism and start mixing with other academic disciplines, Justus Akinsanya, Dean of Health and Social Work, warned last week. PMID- 27657395 TI - Gronuflex adhesive compression bandage. AB - Adequate compression bandaging to reduce lower leg venous hypertension by improving the function of the calf muscle pump is the most important aspect of treating ambulatory patients with venous ulceration. Conventional methods of providing compression, such as paste bandages with other outer forms of support, have been used for many years, but are associated with a number of problems. These include the need for more than one bandage as well as being messy in application and removal, which increases nursing time. Patient discomfort frequently leads to a lack of compliance. In addition to the time spent on bandaging, lack of improvement of skin condition necessitates additional time and cost with the need to apply emollient or other medicaments as part of the therapeutic regimen of patients with venous ulcers. PMID- 27657397 TI - New nursing course a major success. AB - Only four nursing students have left the original intake of 100, after the first year of Oxford Polytechnic's radical new nursing course, according to lecturer Kathy Murphy. PMID- 27657399 TI - A chance for key management role. AB - The 'Strategy for nursing' offers a crucial opportunity to win strong nursing management in the post-reform National Health Service, Royal College of Nursing General Secretary Christine Hancock declared last week. PMID- 27657398 TI - Welcome enthusiasm for Strategy. AB - Nurses' enthusiasm is now working to ensure that 'A strategy for nursing' does not become another lost document on the NHS shelves, Baroness MacFarlane declared last week. PMID- 27657400 TI - Quality can help in light for resources. AB - Nurses must develop proper quality research to fight for resources under the new NHS, Pam Hibbs, City and Hackney District's Chief Nursing Officer told the conference. PMID- 27657401 TI - Keeping tabs on your career. AB - Nurses in Wales are being offered a personal pocket-sized file to enable them to keep an up-to-date 'profile' of their career and qualifications. PMID- 27657402 TI - When is a hot meal an essential service? AB - Nurses may not be involved in determining what is an essential service for patients, and what is a hotel service, according to Stephen Dorrell, Parliamentary Secretary for Health. PMID- 27657403 TI - Nurses facing court appearances. AB - Nurses who live in the nurses' home at a Hertfordshire hospital for the mentally handicapped are to face summonses in court next week for non-payment of the poll tax. PMID- 27657406 TI - Czechoslovakia. AB - Czechoslovakia is to screen explicit commercials advocating the use of condoms, in a bid to combat the spread of HIV. According to official statistics there are only eight people with AIDS in the country but the true number is believed to be as high as 1,000. PMID- 27657404 TI - Pressure sore prophylaxis and care in patients with multiple sclerosis. AB - Sclerosehospitalet at Haslev, Denmark, is a non-profit making institution admitting multiple sclerosis patients. The patients come from all over Denmark, with a majority being from Zealand. Hospitalisation varies between four and eight weeks, depending on individual patient needs. PMID- 27657407 TI - United States. AB - United States Determined lobbying by American nurses has helped secure more funds for AIDS treatment and prevention in the United States. PMID- 27657408 TI - Caring for romania appeal. AB - A well deserved rest at the end of the recent 13 mile sponsored walk by members of the Westmorland Branch RCN. The event was organised by Maureen Higginson, Secretary and Steward, and took place along the canal banks from Stainton to Carnforth. Eight hundred. PMID- 27657410 TI - ? AB - A new video on weaning has been launched for health professionals to use in parentcraft and post natal classes. PMID- 27657412 TI - Unnecessay X-rays should be cut. AB - One fifth of all X-rays carried out in Britain are unnecessary, according to a report from the Royal College of Radiologists (RCR) and the National Radiological Protection Board (NRPB). PMID- 27657411 TI - Abortion pill could save NHS L13.5m. AB - If the abortion pill RU486 is found to be suitable for all first trimester terminations, it could save the NHS L13.5 million a year, it has been claimed. PMID- 27657413 TI - New breathing test may help reduce cot deaths. AB - Babies at risk from cot death could be identified by a test carried out within hours of birth, initial trials suggest. PMID- 27657414 TI - Simple treatment for ruptured hepatoma. AB - Rupture of a hepatoma is a dramatic surgical emergency where bleeding is difficult to control and mortality high. But researchers think they have found a successful treatment. PMID- 27657415 TI - Growth factors and chemotherapy. AB - The neutropenia associated with some chemotherapeutic regimens might be reduced by the use of growth factors. PMID- 27657416 TI - Caution urged in fluconazole treatment. AB - Fluconazole should be used with caution when a long course of therapy might be required or there is pre-existing liver disease. PMID- 27657417 TI - Gastric ulcers and rheumatoid arthritis. AB - Reduced production of epidermal growth factor in saliva might contribute to a susceptibility to gastric ulceration in patients with rheumatoid arthritis (RA) and patients with the sicca syndrome might be a particularly at risk sub-group. PMID- 27657418 TI - Special beds 'can conceal haemorrhage'. AB - Patients being nursed on air fluidised ' beds might be at high risk from concealed haemorrhage, researchers say. PMID- 27657419 TI - Burying the review body? AB - Shots are being fired from all sides at nursing unions as they start this year'spay round with the knowledge that the NHS Director of Personnel wants to see the end of national pay bargaining for nurses. PMID- 27657420 TI - A nurse for the ninetiesA nurse whose inventive work has helped improve treatment for people with leg ulcers has won the Nursing Standard /BUPA nursing nurse 90 award. She received her award this week from health secretary Kenneth Clarke. AB - This week Secretary of State Kenneth Clarke presented a cheque for L3,000 and a commemorative certificate to a nurse whose work revolutionised nursing care. PMID- 27657421 TI - Full steam ahead. AB - Imagine a tropical paradise - swaying palms, the sun beating down on the white sand, the gentle lapping of the waves. A little way out to sea a liner rolls gently in the swell... the stuff of glossy holiday brochures. But behind the glittering facade is often the spectre of poverty, illness and need. PMID- 27657422 TI - Obstructive sleep Apnoea. AB - Despite being an uncommon condition, sleep apnoea is attracting increasing interest among professionals and the lay public. Deborah Casey discusses the causes, symptoms, diagnosis and management of this distressing and on occasion, life-threatening disorder. PMID- 27657423 TI - The link between poverty and health. AB - Events and trends in health and welfare policy have dramatically changed the climate in which families and individuals look after their own health, and health visitors care for their clients. Cuts in public expenditure and extensive restructuring of the health and welfare fields have reduced the role the state plays in health and welfare, placing responsibility for health back with individuals and families. But high levels of unemployment, low pay, taxation policies, and changes to the social security system have reduced the ability of many individuals and families to meet their needs. Moreover, the same social policies have often made it increasingly difficult for health visitors to intervene with other agencies on behalf of families, or to promote individual and family health on a daily basis. PMID- 27657424 TI - The liaison between care and computers. AB - Susan Davis describes the evolvement of her role as liaison nurse in the Royal Marsden's computer department. There is an overview of how this role has helped with the implementation of information technology at grass roots/ward level. The advantages of information technology (IT) for nursing staff are explored and examples are given of how innovations have been helpful in patient care, with rapid availability of blood results for patients on chemotherapy. The importance of support and training for all staff working with IT is also addressed. PMID- 27657425 TI - The criteria for conversion. AB - It's hardly surprising that enrolled nurses arc frustrated, disillusioned and generally fed up with the whole process of trying to convert to first level nurse. PMID- 27657426 TI - Another kind of distance learning? AB - With reference to the news item Library cash crisis to hit P2000 courses' (Nursing Standard September 5), I am sure that all librarians who are now concerned with the implementation of the new courses will be extremely disturbed. PMID- 27657427 TI - Feet of Clay over frilly caps issue. AB - I am delighted to see Trevor Clay back in harness (Nursing Standard September 12 1990). I found the column interesting and challenging. I hope there will be much discussion in the future about autonomy and teamwork. PMID- 27657428 TI - ME: working on a right approach. AB - With reference to your feature on Myalgic Encephalitis (Nursing StandardAugust 29). I am, sorry to read how badly John Brodrick feels he was dealt with by his colleagues, especially those working in the Occupational Health Department. PMID- 27657429 TI - Crossword clues. PMID- 27657430 TI - Changing roles for students. AB - Currently I am doing a BEd course and recently carried out a mini-research assignment using a participant observer approach. PMID- 27657431 TI - Information Exchange. AB - I am a student nurse at Hill End Hospital and am presently working with elderly people in hospital on a project designed to promote reminiscence and socialisation. PMID- 27657432 TI - A forecast of needs. AB - The only demographic changes seen in the last century, comparable to those we arc currently experiencing, were during the two world wars, when the absence of men led to a shortage of workers. PMID- 27657434 TI - Blazing a trail. AB - Coronary heart disease remains the biggest killer in the United Kingdom, despite the trend towards healthier living and much greater public awareness of risk factors. Nearly a quarter of a million people will the this year from the epidemic of heart disease. PMID- 27657433 TI - Multiple Sclerosis. AB - The Multiple Sclerosis Society of Great Britain and Northern Ireland has an impressive publication programme which includes booklets, sheets, periodicals, and audio and video cassettes. The Society provides general information for adults and children whose lives arc affected directly or indirectly by MS; lecture notes and resource packs for the health-care professional; and details of financial assistance. PMID- 27657435 TI - Prevention in practice. AB - The United Kingdom has a high mortality from coronary heart disease in comparison to most other Western countries ( Figure 1 ). Recent figures suggest that there has been a slight reduction in mortality ( 1 ). PMID- 27657436 TI - Coronary regression. AB - Evidence that medical intervention may lead to a reduction in the size of coronary artery stenoses (coronary regression) has gradually accumulated over the last 60 years. PMID- 27657437 TI - Pacemakers. AB - A pacemaker is a battery powered device which generates electrical discharges when the natural mechanism of the heart : fails. It may be fixed rate or demand and is QRS inhibited. The system may be for : temporary or permanent use. The first permanent pacemaker was implanted in Switzerland in 1958 in a patient, Arne Larsson, who had suffered from increasingly irregular cardiac rhythm for some years. PMID- 27657438 TI - Thrombolytic therapy. AB - A myocardial infarction is the end stage of a disease process that begins early in life. A diet rich in saturated fat, smoking and high blood pressure conspire to produce changes in arterial walls. These changes, called atheroma, consist of fibrous fatty deposits in the innermost lining of the blood vessel. The atheromatous deposit or plaque encroaches into the arterial lumen and when it reaches a certain size begins to reduce the rate at which blood flows along the vessel. In the ( case of the coronary circulation this reduction in blood flow deprives the heart muscle of important nutrients and the patient experiences a characteristic discomfort called angina. PMID- 27657439 TI - Thinking outside the box when reading aloud: Between (localist) module connection strength as a source of word frequency effects. AB - The frequency with which words appear in print is a powerful predictor of the time to read monosyllabic words aloud, and consequently all models of reading aloud provide an explanation for this effect. The entire class of localist accounts assumes that the effect of word frequency arises because the mental lexicon is organized around frequency of occurrence (the action is inside the lexical boxes). We propose instead that the frequency of occurrence effect is better understood in terms of the hypothesis that the strength of between module connections varies as a function of word frequency. Findings from 3 different lines of investigation (experimental and computational) are difficult to understand in terms of the "within lexicon" account, but are consistent with the strength of between-module connections account. (PsycINFO Database Record PMID- 27657440 TI - The promise of educational neuroscience: Comment on Bowers (2016). AB - Bowers (2016) argues that there are practical and principled problems with how educational neuroscience may contribute to education, including lack of direct influences on teaching in the classroom. Some of the arguments made are convincing, including the critique of unsubstantiated claims about the impact of educational neuroscience and the reminder that the primary outcomes of education are behavioral, such as skill in reading or mathematics. Bowers' analysis falls short in 3 major respects. First, educational neuroscience is a basic science that has made unique contributions to basic education research; it is not part of applied classroom instruction. Second, educational neuroscience contributes to ideas about education practices and policies beyond classroom curriculum that are important for helping vulnerable students. Third, educational neuroscience studies using neuroimaging have not only revealed for the first time the brain basis of neurodevelopmental differences that have profound influences on educational outcomes, but have also identified individual brain differences that predict which students learn more or learn less from various curricula. In several cases, the brain measures significantly improved or vastly outperformed conventional behavioral measures in predicting what works for individual children. These findings indicate that educational neuroscience, at a minimum, has provided novel insights into the possibilities of individualized education for students, rather than the current practice of learning through failure that a curriculum did not support a student. In the best approach to improving education, educational neuroscience ought to contribute to basic research addressing the needs of students and teachers. (PsycINFO Database Record PMID- 27657441 TI - The principles and practices of educational neuroscience: Comment on Bowers (2016). AB - In his recent critique of Educational Neuroscience, Bowers argues that neuroscience has no role to play in informing education, which he equates with classroom teaching. Neuroscience, he suggests, adds nothing to what we can learn from psychology. In this commentary, we argue that Bowers' assertions misrepresent the nature and aims of the work in this new field. We suggest that, by contrast, psychological and neural levels of explanation complement rather than compete with each other. Bowers' analysis also fails to include a role for educational expertise-a guiding principle of our new field. On this basis, we conclude that his critique is potentially misleading. We set out the well documented goals of research in Educational Neuroscience, and show how, in collaboration with educators, significant progress has already been achieved, with the prospect of even greater progress in the future. (PsycINFO Database Record PMID- 27657442 TI - Psychology, not educational neuroscience, is the way forward for improving educational outcomes for all children: Reply to Gabrieli (2016) and Howard-Jones et al. (2016). AB - In Bowers (2016), I argued that there are (a) practical problems with educational neuroscience (EN) that explain why there are no examples of EN improving teaching and (b) principled problems with the logic motivating EN that explain why it is likely that there never will be. In the following article, I consider the main responses raised by both Gabrieli (2016) and Howard-Jones et al. (2016) and find them all unconvincing. Following this exchange, there are still no examples of EN providing new insights to teaching in the classroom, there are still no examples of EN providing new insights to remedial instructions for individuals, and, as I detail in this article, there is no evidence that EN is useful for the diagnosis of learning difficulties. The authors have also failed to address the reasons why EN is unlikely to benefit educational outcomes in the future. Psychology, by contrast, can (and has) made important discoveries that can (and should) be used to improve teaching and diagnostic tests for learning difficulties. This is not a debate about whether science is relevant to education, rather it is about what sort of science is relevant. (PsycINFO Database Record PMID- 27657443 TI - Approach for Half-Life Extension of Small Antibody Fragments That Does Not Affect Tissue Uptake. AB - The utility of antigen-binding antibody fragments is often limited by their short half-lives. Half-life extension of such fragments is usually accomplished by attachment or binding to high-molecular-weight carriers that reduce the renal elimination rate. However, the higher hydrodynamic radius results in greater confinement in the vascular compartment and, thus, lower tissue distribution. We have developed a chemically controlled drug delivery system in which the drug is covalently attached to hydrogel microspheres by a self-cleaving beta-eliminative linker; upon subcutaneous injection, the t1/2,beta of the released drug acquires the t1/2 of linker cleavage. In the present work, we compared the pharmacokinetics of an anti-TNFalpha scFv, the same scFv attached to 40 kDa PEG by a stable linker, and the scFv attached to hydrogel microspheres by a self cleaving linker. We also developed a general approach for the selective attachment of beta-eliminative linkers to the N-termini of proteins. In rats, the scFv had a t1/2,beta of 4 h and a high volume of distribution at steady state (Vd,SS), suggesting extensive tissue distribution. The PEG-scFv conjugate had an increased t1/2,beta of about 2 days but showed a reduced Vd,SS that was similar to the plasma volume. In contrast, the tissue-penetrable scFv released from the hydrogel system had a t1/2,beta of about 2 weeks. Thus, the cleavable microsphere scFv conjugate releases its protein cargo with a prolonged half-life comparable to that of most full-length mAbs and in a form that has the high tissue distribution characteristic of smaller mAb fragments. Other antigen-binding antibody fragments should be amenable to the half-life extension approach described here. PMID- 27657444 TI - Not Your Father's, or Mother's, Rodent: Moving Beyond B6. AB - In this issue of Neuron, Sittig et al. (2016) present research that calls into question the way laboratory mice are used to address questions in basic science and experimental medicine. This research demonstrates strong interactions between mutant alleles and genetic background. PMID- 27657446 TI - Re-engineering the Hippocampus. AB - As adult-generated neurons integrate into hippocampal circuits, they compete with mature neurons for inputs from the entorhinal cortex. By reducing spines on mature granule cells, McAvoy et al. (2016) find that new neurons integrate more efficiently, and this facilitates learning. PMID- 27657445 TI - Deeper Insights into the Allosteric Modulation of Ionotropic Glutamate Receptors. AB - Two articles in this issue of Neuron (Yelshanskaya et al., 2016; Yi et al., 2016) explore the structural basis of allosteric inhibition in ionotropic glutamate receptors, providing key insights into how iGluRs function in the brain as well as how they might be pharmacologically modulated in neurological disorders and disease. PMID- 27657447 TI - Dopamine Neurons, Input Integration, and Reward Prediction Errors: E Pluribus Unum. AB - Dopamine neurons encode errors in reward prediction, yet understanding how they integrate information from different subcortical inputs to generate these signals has remained elusive. In this issue of Neuron, Tian et al. (2016) shed new light onto these underlying mechanisms. PMID- 27657449 TI - Transformation of the Radial Glia Scaffold Demarcates Two Stages of Human Cerebral Cortex Development. AB - The classic view of cortical development, embodied in the radial unit hypothesis, highlights the ventricular radial glia (vRG) scaffold as a key architectonic feature of the developing neocortex. The scaffold includes continuous fibers spanning the thickness of the developing cortex during neurogenesis across mammals. However, we find that in humans, the scaffold transforms into a physically discontinuous structure during the transition from infragranular to supragranular neuron production. As a consequence of this transformation, supragranular layer neurons arrive at their terminal positions in the cortical plate along outer radial glia (oRG) cell fibers. In parallel, the radial glia that contact the ventricle develop distinct gene expression profile and "truncated" morphology. We propose a supragranular layer expansion hypothesis that posits a deterministic role of oRG cells in the radial and tangential expansion of supragranular layers in primates, with implications for patterns of neuronal migration, area patterning, and cortical folding. PMID- 27657450 TI - Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons. AB - The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants. PMID- 27657448 TI - Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline. AB - Recent work continues to place cholinergic circuits at center stage for normal executive and mnemonic functioning and provides compelling evidence that the loss of cholinergic signaling and cognitive decline are inextricably linked. This Review focuses on the last few years of studies on the mechanisms by which cholinergic signaling contributes to circuit activity related to cognition. We attempt to identify areas of controversy, as well as consensus, on what is and is not yet known about how cholinergic signaling in the CNS contributes to normal cognitive processes. In addition, we delineate the findings from recent work on the extent to which dysfunction of cholinergic circuits contributes to cognitive decline associated with neurodegenerative disorders. PMID- 27657453 TI - Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain. PMID- 27657452 TI - Human Orbitofrontal Cortex Represents a Cognitive Map of State Space. AB - Although the orbitofrontal cortex (OFC) has been studied intensely for decades, its precise functions have remained elusive. We recently hypothesized that the OFC contains a "cognitive map" of task space in which the current state of the task is represented, and this representation is especially critical for behavior when states are unobservable from sensory input. To test this idea, we apply pattern-classification techniques to neuroimaging data from humans performing a decision-making task with 16 states. We show that unobservable task states can be decoded from activity in OFC, and decoding accuracy is related to task performance and the occurrence of individual behavioral errors. Moreover, similarity between the neural representations of consecutive states correlates with behavioral accuracy in corresponding state transitions. These results support the idea that OFC represents a cognitive map of task space and establish the feasibility of decoding state representations in humans using non-invasive neuroimaging. PMID- 27657451 TI - Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains. AB - Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology. PMID- 27657454 TI - Correction. PMID- 27657455 TI - Correction. PMID- 27657456 TI - Correction. PMID- 27657457 TI - The association between leptin receptor gene polymorphisms and type 2 diabetes mellitus: A systematic review and meta-analysis. AB - BACKGROUND: Several case-control studies have demonstrated a relationship between leptin receptor (LEPR) gene polymorphism and type 2 diabetes mellitus (T2DM) risk, though the results have not always been consistent among diverse populations. This meta-analysis was designed to assess a more accurate association between LEPR polymorphism and T2DM. METHODS: Eight electronic databases were consulted and researchers searched for Chinese and English peer reviewed articles, published between 2000 and 2015, that referred to the association between LEPR polymorphism and T2DM. Pooled odds ratios (OR) with a 95% confidence interval (CI) were calculated in allele contrast, recessive, dominant and additive genetic models to assess this association. RESULTS: Four repeatedly reviewed polymorphisms, taken from 22 studies on Arg109Lys, Asn656Lys, Gln223Arg and Pro1019Pro with 31,260 controls and 25,560 cases, were included in the meta-analysis model. The meta-result demonstrated that only the Pro1019Pro polymorphism was substantially associated with T2DM risk-G vs. A: OR with 95% CI 0.58 (0.43-0.79), Z=3.51, p=0.0005; GG vs. AG+AA: 0.57 (0.42-0.77), Z=3.66, p=0.0002; GG+AG vs. AA: 0.55 (0.37-0.81), Z=3.01, p=0.003; GG vs. AA: 0.51 (0.37 0.69), Z=4.24, p<0.001. CONCLUSIONS: Our meta-analysis suggested a significant association between the LEPR Pro1019Pro polymorphism and T2DM risk. Thus, targeted healthcare should be strengthened with regard to this gene carrier in order to prevent T2DM. PMID- 27657458 TI - A novel compound heterozygous mutation in an adolescent with insulin-dependent diabetes: The challenge of characterizing Wolfram syndrome. AB - WS diagnosis is often delayed since misdiagnosed as autoimmune diabetes. The rarity of the condition and the absence of other diseases at diabetes diagnosis might make extremely challenging the recognition of WS. However the novel compound heterozygosity for the here reported mutations, seems to confer a mild phenotype among the spectrum of WS manifestations. PMID- 27657459 TI - Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India. AB - LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30ugl-1 as well as AERB proposed limit of 60ugl-1. Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60ugl-1. Average value observed in SW Punjab is around 3-4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. PMID- 27657460 TI - Calibration of a low background gas-flow proportional counter to estimate 234Th activity in coastal waters. AB - This paper relates the calibration of a low background gas-flow proportional counter. This calibration has been used to determine low activity of 234Th in coastal water samples. Two methods were used to prepare calibration samples: Evaporation and Electrodeposition. First method was rejected due to the lack of reproducibility because the different geometry adopted by the drops of tracer once dried on the disk. On the contrary, through the second method, similar efficiencies were obtained in all detectors with an average of 0.401+/-0.004. In this paper, the whole procedure to obtain 234Th activity in dissolution as well as in particulate matter has been detailed, and all the algorithms needed to calculate activities and efficiencies are shown. Finally, two experiments have been designed in order to validate the calibration of the beta counter and the method to determine 234Th in coastal waters with high concentration of particulate matter. PMID- 27657461 TI - Phosphate Ester Bond Hydrolysis Promoted by Lanthanide-Substituted Keggin-type Polyoxometalates Studied by a Combined Experimental and Density Functional Theory Approach. AB - Hydrolytic cleavage of 4-nitrophenyl phosphate (NPP), a commonly used DNA model substrate, was examined in the presence of series of lanthanide-substituted Keggin-type polyoxometalates (POMs) [Me2NH2]11[CeIII(PW11O39)2], [Me2NH2]10[CeIV(PW11O39)2] (abbreviated as (CeIV(PW11)2), and K4[EuPW11O39] by means of NMR and luminescence spectroscopies and density functional theory (DFT) calculations. Among the examined complexes, the Ce(IV)-substituted Keggin POM (CeIV(PW11)2) showed the highest reactivity, and its aqueous speciation was fully determined under different conditions of pD, temperature, concentration, and ionic strength by means of 31P and 31P diffusion-ordered NMR spectroscopy. The cleavage of the phosphoester bond of NPP in the presence of (CeIV(PW11)2) proceeded with an observed rate constant kobs = (5.31 +/- 0.06) * 10-6 s-1 at pD 6.4 and 50 degrees C. The pD dependence of NPP hydrolysis exhibits a bell-shaped profile, with the fastest rate observed at pD 6.4. The formation constant (Kf = 127 M-1) and catalytic rate constant (kc = 19.41 * 10-5 s-1) for the NPP-Ce(IV) Keggin POM complex were calculated, and binding between CeIV(PW11)2 and the phosphate group of NPP was also evidenced by the change of the chemical shift of the 31P nucleus in NPP upon addition of the POM complex. DFT calculations revealed that binding of NPP to the parent catalyst CeIV(PW11)2 is thermodynamically unlikely. On the contrary, formation of complexes with the monomeric 1:1 species, CeIVPW11, is considered to be more favorable, and the most stable complex, [CeIVPW11(H2O)2(NPP-kappaO)2]7-, was found to involve two NPP ligands coordinated to the CeIVcenter of CeIVPW11 in the monodentate fashion. The formation of such species is considered to be responsible for the hydrolytic activity of CeIV(PW11)2 toward phosphomonoesters. On the basis of these findings a principle mechanism for the hydrolysis of NPP by the POM is proposed. PMID- 27657462 TI - Phosphorylated Epidermal Growth Factor Receptor Expression Is Associated With Clinicopathologic Parameters and Patient Survival in Mobile Tongue Squamous Cell Carcinoma. AB - PURPOSE: Phosphorylated epidermal growth factor receptor (pEGFR) activates several signaling pathways, resulting in tumor-promoting cellular activities, and has been implicated in malignant transformation and disease progression. The present study evaluated the clinical significance of pEGFR protein expression in mobile tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: The present cohort study included 48 patients with mobile tongue SCC. We evaluated whether pEGFR immunohistochemical protein expression is associated with clinical variables and patient outcome. RESULTS: Of the 48 patients included in the present cohort study, 25 were men and 23 were women. The median patient age was 60 years (interquartile range 53 to 72). pEGFR protein expression was significantly increased in well-differentiated tumors compared with poorly differentiated tumors (P = .001). Elevated pEGFR protein expression was significantly more frequently observed in mobile tongue SCC cases with a well defined tumor shape and an earlier disease stage (P = .010 and P = .019, respectively). Patients with mobile tongue SCC presenting with elevated pEGFR expression had longer overall and disease-free survival times compared with those with low pEGFR expression (P = .015 and P = .006, respectively; log-rank test). On multivariate analysis, pEGFR expression proved to be an independent prognostic factor of both overall and disease-free survival (P = .008 and P = .044, respectively; Cox regression analysis). CONCLUSIONS: The results of the present study support evidence that the pEGFR signaling pathway might be implicated in the malignant transformation of mobile tongue SCC. Additional studies are recommended to validate whether pEGFR could be used as a potential biomarker and therapeutic target in mobile tongue SCC. PMID- 27657463 TI - Effect of ivabradine on central aortic blood pressure in patients with stable coronary artery disease: What do we know? AB - Treatment of hypertensive patients with beta-blockers decreases central blood pressure (CBP) less than other antihypertensive drugs, which is believed to account for their lesser cardiovascular protection in this setting. Some authors have suggested that decreasing heart rate (HR) with beta-blockers would increase CBP. In contrast to beta-blockers, the anti-anginal agent ivabradine reduces HR without other hemodynamic effects, and represents an attractive tool for exploring the direct relationship between HR and CBP. Here, we review the available clinical data assessing the effect of selective HR reduction with ivabradine on CBP in patients with stable coronary artery disease (CAD). We collected data from five studies which report either increase, decrease, or neutral effects of ivabradine on CBP. Further studies are needed to clarify the exact role of ivabradine on CBP. However, as supported by its pharmacodynamic effect in patients with stable CAD, available evidence to date suggests that ivabradine does not negatively impact CBP when associated with beta-blocker. HR reduction with both beta-blockers and ivabradine remains well-established treatments for the symptomatic treatment of angina patients. PMID- 27657464 TI - Creating bidirectional conduction block in the cavotricuspid isthmus by cryothermal ablation with a short freeze time: Insight from the results with a 2 minute freeze cycle. AB - BACKGROUND: Optimal freeze doses are unknown during cryothermal cavo-tricuspid isthmus (CTI) ablation. This study aimed to evaluate the feasibility of 2-minute freeze doses for CTI ablation. METHODS: Forty-eight consecutive patients undergoing cryothermal CTI ablation following pulmonary vein isolation were enrolled. CTI ablation was performed with 2-minute freeze cycles and 8-mm tip cryocatheters. RESULTS: Bidirectional CTI block was successfully achieved in 45(93.8%) patients with a median of 5.0[4.0-6.0] cryocatheter applications. The total procedure and fluoroscopic times were a median of 16.5[13.0-20.0] and 4.0[2.0-5.0]min, respectively. A crossover to radiofrequency was performed in 3 patients including 1 due to coronary spasms during the cryoapplication. The tip temperature when block was achieved was a median of -81.0[-73.3 - -84.0] degrees C. Application times from the start of the last application to achieving block were significantly longer in patients with acute conduction resumption than in those without (46.8+/-4.0 vs. 20.2+/-8.8s, p<0.0001), and the optimal cutoff point for predicting no acute resumption was 38.5s (sensitivity 100%, specificity 99.5%). Vasospastic angina occurred in 2 patients, during the procedure in 1 and after in another. Durability could be evaluated a median of 6.0[3.0-8.0] months after the procedure in 14 patients, and conduction resumption was observed in 8(57.1%). The majority of gaps were located at the inferior vena cava edge. CONCLUSIONS: Acute CTI block was obtained by 2-minute freeze cycles with short procedure and fluoroscopic times. Care should be taken to avoid coronary spasms during the peri-procedural period. Additional cryoapplications might be required to improve conduction block durability. PMID- 27657465 TI - Serum potassium on mortality risk among a national sample of cardiovascular disease patients: Considerations by physical activity. PMID- 27657466 TI - Lactobacillus paracasei endocarditis in a consumer of probiotics with advanced and severe bicuspid aortic valve stenosis complicated with diffuse left ventricular mid-layer fibrosis. PMID- 27657467 TI - Accuracy of administrative data for identification of patients with infective endocarditis. AB - BACKGROUND: Infective endocarditis is associated with high morbidity and mortality rates that have plateaued over recent decades. Research to improve outcomes for these patients is limited by the rarity of this condition. Therefore, we sought to validate administrative database codes for the diagnosis of infective endocarditis. METHODS: We conducted a retrospective validation study of International Classification of Diseases (ICD-10-CM) codes for infective endocarditis against clinical Duke criteria (definite and probable) at a large acute care hospital between October 1, 2013 and June 30, 2015. To identify potential cases missed by ICD-10-CM codes, we also screened the hospital's valvular heart surgery database and the microbiology laboratory database (the latter for patients with bacteremia due to organisms commonly causing endocarditis). RESULTS: Using definite Duke criteria or probable criteria with clinical suspicion as the reference standard, the ICD-10-CM codes had a sensitivity (SN) of 0.90 (95% confidence interval (CI), 0.81-0.95), specificity (SP) of 1 (95% CI, 1-1), positive predictive value (PPV) of 0.78 (95% CI, 0.68 0.85) and negative predictive value (NPV) of 1 (95% CI, 1-1). Restricting the case definition to definite Duke criteria resulted in an increase in SN to 0.95 (95% CI, 0.86-0.99) and a decrease in PPV to 0.6 (95% CI, 0.49-0.69), with no change in specificity. CONCLUSION: ICD-10-CM codes can accurately identify patients with infective endocarditis, and so administrative databases offer a potential means to study this infection over large jurisdictions, and thereby improve the prediction, diagnosis, treatment and prevention of this rare but serious infection. PMID- 27657469 TI - Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies. AB - Heart failure (HF) is a burgeoning chronic health condition affecting more than 20million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach. PMID- 27657468 TI - Comparison of echocardiographic parameters between pre-clinical and clinical advanced diastolic dysfunction patients. AB - BACKGROUND: The diagnosis of heart failure (HF) with preserved ejection fraction requires evidence of grade 2 or 3 (advanced) diastolic dysfunction (ADD), but many patients with ADD do not have clinical HF manifestations, hence termed pre clinical diastolic dysfunction (PDD). The prevalence and characteristics of PDD in comparison to overt HF disease (clinical-ADD) are still debated. METHODS: We retrospectively analyzed 373 patients with LVEF>=45% and ADD in our echo-lab database. Exclusion criteria were acute coronary syndromes, >=moderate valvular disease, cardiomyopathies or pericardial disease. Patients were divided into 2 groups according to the presence/absence of HF symptoms, namely PDD (n=249) and clinical-ADD (n=124). Demographic, clinical and echocardiographic parameters were compared between the groups. RESULTS: Age, gender and comorbidities were similar between groups, with only a higher body mass index and renal failure significantly more prevalent in the clinical-ADD patients. Neither LV mass nor the ADD severity was related to the presence of symptoms; lateral mitral E/E' and pulmonary artery systolic pressure were significantly higher in clinical-ADD patients (14+/-5 vs. 12+/-4, p<0.05 and 40+/-13 vs. 36+/-11mmHg, p<0.05, respectively) and were the only parameters to correlate with the presence of symptoms of clinical-ADD in multivariable logistic regression (odds ratio=1.07 (CI 1.02-1.1, p=0.008) and 1.03 (CI 1.01-1.05, p=0.01), respectively). CONCLUSIONS: In patients referred for an echocardiogram at a community cardiology center, PDD was twice as common as clinical-ADD. Hemodynamic parameters reflecting elevated filling and pulmonary pressures, rather than traditional comorbidities and/or classical structural abnormalities, were the only parameters related to the presence of HF symptoms. PMID- 27657470 TI - High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest. AB - BACKGROUND: The number of people living in high-rise buildings has recently been increasing in Japan, and delayed transport time by emergency-medical-service (EMS) personnel from higher floors could lead to lower survival after out-of hospital cardiac arrest (OHCA). However, there are no clinical studies assessing the association between the floor where patients reside and neurologically favorable outcome after OHCA. METHODS: This was a prospective, population-based study conducted in Osaka City, Japan that enrolled adults aged >=18years suffering an OHCA of cardiac origin before EMS arrival between 2013 and 2014. The primary outcome measure was one-month survival with neurologically favorable outcome. We divided OHCA patients into the following groups: those residing on >=3 floors (the high floor group) and <3 floors (the low floor group). Multiple logistic regression analysis was used to assess factors associated with neurologically favorable outcome. RESULTS: A total of 2979 patients were eligible for analysis. Of them, 1885 (62.3%) occurred below the third floor and 1094 (37.4%) occurred at or above the third floor. The proportion of neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (2.7% [30/1094] versus 4.8% [91/1885], P=0.005). In a multivariate analysis, neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (adjusted odds ratio, 0.59 [95% confidence interval, 0.37-0.96]). CONCLUSIONS: In this population, one-month survival with neurologically favorable outcome from OHCA was lower in the high floor group than in the low floor group. PMID- 27657471 TI - Oral nicorandil reduces ischemic attacks in patients with stable angina: A prospective, multicenter, open-label, randomized, controlled study. AB - OBJECTIVE: To evaluate the efficacy and safety of oral nicorandil in coronary heart disease (CHD) patients with stable angina. METHOD: Eligible patients were randomized 1:1 to the nicorandil or control group. Current standard antianginal treatment was continued in both groups, while the patients in the nicorandil group received an additional 12-week treatment of nicorandil (5mg thrice daily). Primary endpoint was the number of myocardial ischemia measured by 24h Holter after 12-week treatment. Secondary endpoints included various 24h Holter indicators, angina occurrence, 6-min walking test (6MWT), ECG QT dispersion (QTd), safety and compliance. CLINICAL TRIAL REGISTRATION: NCT01396395. RESULTS: A total of 402 adult patients with stable angina were enrolled. Two hundred patients were randomized to standard therapy plus nicorandil and 202 patients to standard therapy only. The baseline characteristics of the two groups were comparable. The number of myocardial ischemia attacks after treatment was significantly lower in the nicorandil group (LSMEANS 0.896) than the control group (LSMEANS 1.782), with an adjusted ratio of 0.503 (95% CI: 0.301, 0.840; P=0.0086). No significant differences in total myocardial ischemic burden, maximum ST-depression, longest duration of ST-depression, 6MWT, or heart rate variability were noted between the two groups. Twenty three (11.7%) of nicorandil group and 13 (6.3%) patients of control group reported at least one treatment emergent adverse event, respectively. CONCLUSION: Nicorandil significantly reduced the number of ischemic attacks when added to standard antianginal treatment in CHD patients with stable angina. It was well tolerated with no new safety signal identified. PMID- 27657472 TI - Height and prognosis following percutaneous coronary intervention. PMID- 27657473 TI - Pharmacokinetics and pharmacodynamics of cardiovascular drugs in chronic heart failure. AB - Pharmacotherapy in chronic heart failure (HF) is challenging, due to the diverse neuroendocrine, inflammatory, metabolic and immunological mechanisms involved in its pathogenesis, the presence of co-morbidities and use of multiple therapies. Further, physiological parameters influencing drug pharmacokinetics (PKs) and pharmacodynamics (PDs) may be altered in patients with HF. There is growing evidence that the disease-induced physiological changes may influence the PKs and PDs of all drugs used in patients with HF. Therapeutic approaches should consider all factors that might influence the response to treatment and dosage should be tailored to individual patients. Hence, further studies are required to understand the PK and PD differences between chronic HF patients and healthy subjects. Because PK is difficult to be assessed in the individual patient with HF, PD effects should be used to tailor therapy in patients with HF. PMID- 27657474 TI - New electrocardiographic criteria for predicting successful ablation of premature ventricular contractions from the right coronary cusp. AB - BACKGROUND: ECG features for predicting successful ablation sites of outflow tract (OT) premature ventricular complex (PVCs) have been previously presented, but effective predictors of right coronary cusp (RCC) remain elusive. METHODS: 106 patients (59 males, 56+/-14years) who underwent successful PVC ablation were studied. Various ECG patterns and measurements were analyzed to identify the unique features of RCC PVC origins. The R-wave duration index (RWDI) was calculated as a percentage by dividing the QRS complex duration by the longest R wave duration in lead V1 or V2. RESULTS: Successful ablation sites were the RCC in 18 patients, the left coronary cusp (LCC) in 20, the RCC/LCC junction (RLJ) in 22, the AIV/GCV in 11 and the right ventricular outflow tract in 35. Forty-seven patients had dominantly positive forces in lead I. Among these 47 patients, 19 were ablated from the RCC (18/18, 100%), eighteen from the RVOT (18/35, 51%), five from the LCC (5/20, 25%), and five from the RLJ (6/22, 27%). The S-wave amplitude in lead aVL was significantly smaller in RCC than LCC or RLJ PVCs (0.1+/-0.3mV vs. 1.1+/-0.5mV, p<0.001). The V1-2 RWDI was significantly greater in RCC than RVOT PVCs (51.8+/-20.5% vs. 30.8+/-13.9%, p<0.001). The optimal cut off values of <0.95mV for S-wave (area under the curve, AUC: 0.76, p<0.01) and >43.6% for R-wave duration index in V1 or V2 (AUC: 0.83, p<0.001) were determined by ROC analysis. CONCLUSIONS: The presence of a dominant positive lead I, RWDI >43.6% and S-wave amplitude in aVL <0.95mV predicted RCC PVCs with a sensitivity of 83% and specificity of 94%. PMID- 27657476 TI - Different diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance. AB - BACKGROUND: The question regarding the correct balance between optimal loop diuretic dose administration and best modality is under debate as well as the exact relation existing between congestion and renal dysfunction. We sought to evaluate the effects of different diuretic modalities (low [LD] versus high dose [HD]) and dose administration on decongestion, Worsening renal function (WRF) and outcome. METHODS: We retrospectively analyzed data of DIUR-HF study matching for LD vs HD (cut off 125mg/day), and diuretic efficiency (DE) (weight loss/40mg daily of furosemide). We also evaluated WRF rate (creatinine increase during hospitalization >=0.3mg/dl or estimated glomerular filtration rate (eGFR) reduction >=25%) together with decongestion. RESULTS: HD patients (n.55) were older, more frequently affected by diabetes and chronic kidney disease (CKD) and demonstrated higher rate of inhospital WRF (65% vs 29% p=0.001) and 180-days adverse events (70% vs 23% p<0.001) respect to LD patients (n.41). Patients with low DE showed a higher 180days adverse events rate than higher DE patients (p=0.02). Univariate and multivariable analysis suggests a significant relationship between adverse events and low DE (patients with DE under median value) (U-HR=2.59 [1.44-4.64]; p=0.001. M-HR=3.16 [1.55-6.46]; p=0.002); continuous administration (HR=3.12 [1.65-5.91]; p<0.001) and WRF (HR=5.30 [2.79 10.09]; p<0.001) were also related with adverse events. CONCLUSIONS: HD and poor DE are two conditions associated with adverse outcome. Both situations are the consequence of previous detrimental clinical status and they appear strictly related to WRF occurrence. PMID- 27657475 TI - CXCL12 prolongs naive CD4+ T lymphocytes survival via activation of PKA, CREB and Bcl2 and BclXl up-regulation. AB - BACKGROUND: Naive T lymphocytes recirculate through the body, traveling from secondary lymphoid organs through tissues and via lymphatic vessels and peripheral blood into other secondary lymphoid organs and into the bone marrow. In these tissues, lymphocytes are exposed to the chemokine CXCL12 which is abundantly produced in bone marrow and in lymph nodes by stromal cells. CXCL12 is known to drive lymphocytes chemotaxis and, in cells types such as stem cells, an antiapopototic effect has been described. METHODS: Here we analyzed the effect of CXCL12 exposure on naive CD4+ T lymphocytes purified from peripheral blood by immunomagnetic negative isolation and cultured in a nutrient poor medium. We also studied, mainly by western blot analysis, the signaling pathways involved in CXCL12 action on naive CD4+ T lymphocytes. RESULTS: We found that CXCL12-exposed cells survived longer than untreated ones and this prolonged lifespan was specific for resting naive lymphocytes, while in vitro activated lymphoblasts died rapidly despite CXCL12 treatment. We demonstrated that the increased percentage of living cells observed upon CXCL12 administration was not due to induction of proliferation but to a prosurvival effect of this chemokine. Moreover, our data suggest that this prosurvival effect on naive CD4+ T lymphocytes might likely be mediated by PKA-dependent CREB activation and consequent increased expression of the antiapoptotic factors Bcl2 and BclXl. CONCLUSIONS: This newly reported activity of CXCL12 might contribute to the maintenance of the naive T lymphocytes pool in vivo, which is needed to ensure a proper immune response to new antigens. PMID- 27657477 TI - A low plasma 1,25(OH)2 vitamin D/PTH (1-84) ratio predicts worsening of renal function in patients with chronic heart failure. AB - BACKGROUND: Dysregulation of the vitamin D system promotes renal dysfunction and has direct detrimental effects on the heart. Progressive deterioration of renal function is common in patients with chronic heart failure (HF) and is invariably associated with unfavorable outcomes which can be improved by early identification and timely interventions. We examined the relation between two plasma markers of vitamin D metabolism and worsening of renal function (WRF) in a large cohort of patients with chronic HF. METHODS: Plasma levels of 1,25 dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone PTH (1-84) were measured in 1237 patients with clinical evidence of chronic and stable HF enrolled in the multicentre GISSI-HF trial and followed for 3.9years. We examined the relation of 1,25(OH)2D, PTH(1-84), and their ratio with WRF, defined as first increase in serum creatinine concentration >=0.3mg/dL and >=25% at two consecutive measurements at any time during the study. RESULTS: Lower 1,25(OH)2D/PTH(1-84) ratio was associated with a higher baseline serum concentration of creatinine, winter season, female sex and older age; 335 patients (29.6%) experienced an episode of WRF. After adjustment, a lower 1,25(OH)2D/PTH(1-84) ratio remained significantly associated with a higher risk of WRF (HR=0.75 [0.62-0.90], p=0.002) and correctly reclassified events. This ratio also independently predicted mortality and admission to hospital for cardiovascular reasons. CONCLUSIONS: The plasma 1,25(OH)2D/PTH(1-84) ratio is a promising indicator of future risk of deterioration of renal function in patients with chronic HF and mild renal impairment, that may serve to optimize therapies and improve outcomes. PMID- 27657478 TI - Fourier Transform Ultrasound Spectroscopy for the determination of wave propagation parameters. AB - The reported results for ultrasonic wave attenuation constant (alpha) in pure water show noticeable inconsistency in magnitude. A "Propagating-Wave" model analysis of the most popular pulse-echo technique indicates that this is a consequence of the inherent wave propagation characteristics in a bounded medium. In the present work Fourier Transform Ultrasound Spectroscopy (FTUS) is adopted to determine ultrasonic wave propagation parameters, the wave number (k) and attenuation constant (alpha) at 1MHz frequency in tri-distilled water at room temperature (25 degrees C). Pulse-echo signals obtained under same experimental conditions regarding the exciting input signal and reflecting boundary wall of the water container for various lengths of water columns are captured. The Fast Fourier Transform (FFT) components of the echo signals are taken to compute k, alpha and r, the reflection constant at the boundary, using Oak Ridge and Oxford method. The results are compared with existing literature values. PMID- 27657479 TI - Deconvolution of acoustically detected bubble-collapse shock waves. AB - The shock wave emitted by the collapse of a laser-induced bubble is detected at propagation distances of 30, 40and50mm, using a PVdF needle hydrophone, with a non-flat end-of-cable frequency response, calibrated for magnitude and phase, from 125kHz to 20MHz. High-speed shadowgraphic imaging at 5*106 frames per second, 10nstemporal resolution and 256 frames per sequence, records the bubble deflation from maximum to minimum radius, the collapse and shock wave generation, and the subsequent rebound in unprecedented detail, for a single sequence of an individual bubble. The Gilmore equation for bubble oscillation is solved according to the resolved bubble collapse, and simulated shock wave profiles deduced from the acoustic emissions, for comparison to the hydrophone recordings. The effects of single-frequency calibration, magnitude-only and full waveform deconvolution of the experimental data are presented, in both time and frequency domains. Magnitude-only deconvolution increases the peak pressure amplitude of the measured shock wave by approximately 9%, from single-frequency calibration, with full waveform deconvolution increasing it by a further 3%. Full waveform deconvolution generates a shock wave profile that is in agreement with the simulated profile, filtered according to the calibration bandwidth. Implications for the detection and monitoring of acoustic cavitation, where the role of periodic bubble collapse shock waves has recently been realised, are discussed. PMID- 27657480 TI - Sonodynamic action of hypocrellin B triggers cell apoptoisis of breast cancer cells involving caspase pathway. AB - OBJECTIVES: The aim of the present study is to investigate the effects of sonodynamic action of hypocrellin B on human breast cancer cells and further explore its underlying mechanisms. METHODS: The cell viability of breast cancer MDA-MB-231 cells was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Alterations on cell apoptosis, intracellular reactive oxygen species generation (ROS), mitochondrial membrane potential, and DNA fragmentation was analyzed by flow cytometer. The subcellular localization of hypocrellin B was assessed by a confocal laser scanning microscope. Mitochondria damage and nuclear morphological changes were observed under a fluorescence microscope. To further explore whether caspase pathway was involved in cell apoptotic induction of sonodynamic action of hypocrellin B, the pan-caspase inhibitor Z-Val-Ala-DL-Asp (ome)-Fluoromethylketone (z-VAD-fmk) was added to the cells one hour prior to loading the sonosensitizer, and then cell viability and apoptosis were analyzed after hypocrellin B treatment. RESULTS: Sonodynamic treatment of hypocrellin B HB significantly suppressed cell viability of MDA-MB 231 cells. Sonodynamic action of hypocrellin B caused excessive ROS accumulation, mitochondrial dysfunction, cell apoptosis, DNA fragmentation and nuclear morphological damage. Moreover, the cytotoxicity and cell apoptosis induced by sonodynamic action of hypocrellin B were remarkably rescued by the caspase spectrum inhibitor z-VAD-fmk. CONCLUSIONS: These results demonstrated that hypocrellin B had significant sonodynamic killing and apoptotic induction effect on breast cancer cells. And cell apoptosis induced by sonodynamic action of hypocrellin B was partly dependent on caspase pathway. PMID- 27657481 TI - Rayleigh-type waves in nonlocal micropolar solid half-space. AB - Propagation of Rayleigh type surface waves in nonlocal micropolar elastic solid half-space has been investigated. Two modes of Rayleigh-type waves are found to propagate under certain approximations. Frequency equations of these Rayleigh type modes and their conditions of existence have been derived. These frequency equations are found to be dispersive in character due to the presence of micropolarity and nonlocality parameters in the medium. One of the frequency equations is a counterpart of the classical Rayleigh waves and the other is new and has appeared due to micropolarity of the medium. Phase speeds of these waves are computed numerically for Magnesium crystal and their variation against wavenumber are presented graphically. Comparisons have been made between the phase speeds of Rayleigh type waves through nonlocal micropolar, local micropolar and elastic solid half-spaces. PMID- 27657482 TI - Protective effect of isoquercitrin against acute dextran sulfate sodium-induced rat colitis depends on the severity of tissue damage. AB - BACKGROUND: Isoquercitrin (quercetin-3-O-beta-d-glucopyranoside) is a flavonoid that exhibited antioxidant and anti-inflammatory activities in a number of in vitro and in vivo studies. Experimental evidence from rodent models of inflammatory bowel disease is, however, lacking. This study was designed to examine whether isoquercitrin effectively and dose-dependently attenuates acute dextran sulfate sodium (DSS)-induced rat colitis. METHODS: Wistar rats were divided into negative control group (exposed to vehicle only), positive control group (DSS-induced colitis plus vehicle), low isoquercitrin group (DSS pretreated with isoquercitrin 1mg/kg/day) and high isoquercitrin group (DSS with isoquercitrin 10mg/kg/day). Isoquercitrin was administered daily for 14days, and during the last 7days rats drank DSS solution. The effect of isoquercitrin on DSS induced colitis was assessed clinically (e.g. disease activity index), biochemically (tissue myeloperoxidase activity, local cyclooxygenase-2 expression), using histology (standard hematoxylin-eosin-based histomorphometry, immunohistochemical detection of inducible nitric oxide synthase) and hematology (blood count). RESULTS: Isoquercitrin dose-dependently ameliorated whole colon shortening and mitigated DSS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase in the descending segment of the organ. However, when different parts of colon were assessed histomorphometrically, the results did not globally support the protective role of this flavonoid. Tissue healing trends observable in the descending colon were not apparent in the rectum, where histological damage was most severe. CONCLUSIONS: We surmise that isoquercitrin may be effective in the prevention of acute colitis. Besides being dose dependent, the potency of orally administered isoquercitrin may depend on the severity of tissue damage and/or on the site of its action. PMID- 27657483 TI - The impact of 1MeTIQ on the dopaminergic system function in the 6-OHDA model of Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder which is caused by degeneration of dopaminergic neurons of the nigrostriatal pathway. As a model of PD we used 6-hydroxydopamine (6-OHDA) which exerts toxic effects on catecholaminergic neurons and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) as neuroprotective compound. The aim of the present study, was to investigate the potential neuroprotective properties of 1MeTIQ against 6-OHDA induced neurotoxic effects in the rat. METHODS: In the behavioral study, we measured locomotor activity and catalepsy. In the biochemical studies using HPLC methodology, we analyzed the concentration of dopamine and its metabolites in rat brain. RESULTS: Behavioral tests showed that 6-OHDA decreased rat locomotor activity and produced an increase of catalepsy. These effects did not blocked by 1MeTIQ injections. Biochemical studies indicated that 6-OHDA lesion significantly reduced the concentration of dopamine and its metabolites in the nigro-striatal pathway in the lesioned (ipsilateral) side. Moreover, 6-OHDA induced an increase in the rate of dopamine oxidation. Both acute and chronic administration of 1MeTIQ did not reverse the effects of 6-OHDA lesion on the ipsilateral side, however, it produced a significant elevation of the dopamine concentration in the contralateral side. It is evident that multiple treatments with 1MeTIQ stimulate undamaged neurons to increased activity. CONCLUSION: 1MeTIQ was shown to possess neuroprotective potential to the dopaminergic neurons damaged by 6-OHDA lesion. This compound has a protective effect but does not have neurorestorative capacity. It does not reverse damage already caused but will maintain the function and activity of undamaged dopamine neurons at physiological level. PMID- 27657484 TI - Possible involvement of ATP-sensitive potassium channels in the antidepressant like effect of baclofen in mouse forced swimming test. AB - BACKGROUND: Previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (KATP), in the present study we investigated the involvement of KATP channels in antidepressant like effect of baclofen in the forced swimming test (FST). METHODS: After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of KATP channels, after determination of sub effective doses of glibenclamide as a KATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. RESULTS: Baclofen at dose 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant like effect of baclofen (1mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. CONCLUSIONS: Our study for the first time revealed that antidepressant-like effect of baclofen on mice is KATP-dependent, and baclofen seems that exert this effect by blocking the KATP channels. PMID- 27657485 TI - Low protein feeding and energy transduction in rats. PMID- 27657486 TI - Extending the Power-Law Hemolysis Model to Complex Flows. AB - Hemolysis (damage to red blood cells) is a long-standing problem in blood contacting devices, and its prediction has been the goal of considerable research. The most popular model relating hemolysis to fluid stresses is the power-law model, which was developed from experiments in pure shear only. In the absence of better data, this model has been extended to more complex flows by replacing the shear stress in the power-law equation with a von Mises-like scalar stress. While the validity of the scalar stress also remains to be confirmed, inconsistencies exist in its application, in particular, two forms that vary by a factor of 2 have been used. This article will clarify the proper extension of the power law to complex flows in a way that maintains correct results in the limit of pure shear. PMID- 27657487 TI - Cerenkov Radiation Induced Photodynamic Therapy Using Chlorin e6-Loaded Hollow Mesoporous Silica Nanoparticles. AB - Traditional photodynamic therapy (PDT) requires external light to activate photosensitizers for therapeutic purposes. However, the limited tissue penetration of light is still a major challenge for this method. To overcome this limitation, we report an optimized system that uses Cerenkov radiation for PDT by using radionuclides to activate a well-known photosensitizer (chlorin e6, Ce6). By taking advantage of hollow mesoporous silica nanoparticles (HMSNs) that can intrinsically radiolabel an oxophilic zirconium-89 (89Zr, t1/2 = 78.4 h) radionuclide, as well as possess great drug loading capacity, Ce6 can be activated by Cerenkov radiation from 89Zr in the same nanoconstruct. In vitro cell viability experiments demonstrated dose-dependent cell deconstruction as a function of the concentration of Ce6 and 89Zr. In vivo studies show inhibition of tumor growth when mice were subcutaneously injected with [89Zr]HMSN-Ce6, and histological analysis of the tumor section showed damage to tumor tissues, implying that reactive oxygen species mediated the destruction. This study offers a way to use an internal radiation source to achieve deep-seated tumor therapy without using any external light source for future applications. PMID- 27657488 TI - Polar Second-Harmonic Imaging to Resolve Pure and Mixed Crystal Phases along GaAs Nanowires. AB - In this work, we report an optical method for characterizing crystal phases along single-semiconductor III-V nanowires based on the measurement of polarization dependent second-harmonic generation. This powerful imaging method is based on a per-pixel analysis of the second-harmonic-generated signal on the incoming excitation polarization. The dependence of the second-harmonic generation responses on the nonlinear second-order susceptibility tensor allows the distinguishing of areas of pure wurtzite, zinc blende, and mixed and rotational twins crystal structures in individual nanowires. With a far-field nonlinear optical microscope, we recorded the second-harmonic generation in GaAs nanowires and precisely determined their various crystal structures by analyzing the polar response for each pixel of the images. The predicted crystal phases in GaAs nanowire are confirmed with scanning transmission electron and high-resolution transmission electron measurements. The developed method of analyzing the nonlinear polar response of each pixel can be used for an investigation of nanowire crystal structure that is quick, sensitive to structural transitions, nondestructive, and on-the-spot. It can be applied for the crystal phase characterization of nanowires built into optoelectronic devices in which electron microscopy cannot be performed (for example, in lab-on-a-chip devices). Moreover, this method is not limited to GaAs nanowires but can be used for other nonlinear optical nanostructures. PMID- 27657489 TI - Unmet Needs for Ancillary Services Among Men Who Have Sex with Men and Who Are Receiving HIV Medical Care - United States, 2013-2014. AB - Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV) in the United States (1). Ancillary services, defined as services that support retention in HIV medical care and assist with day-to-day living, can improve the health of HIV-infected MSM and help them achieve viral suppression (2). To assess the unmet needs for ancillary services among MSM receiving outpatient HIV medical care during 2013 2014, CDC used data from the Medical Monitoring Project (MMP), a surveillance system designed to assess clinical and behavioral characteristics of adults receiving HIV care, to obtain nationally representative estimates of, and identify reasons for, unmet needs (3). Based on self-reported needs of persons responding to the MMP survey, the most prevalent unmet needs were for non-HIV medical care services: approximately 23% had an unmet need for dental care, and 19% had an unmet need for eye or vision care. Unmet needs were most prevalent among young, non-Hispanic black, and Hispanic/Latino MSM. State and local health departments, community-based organizations, and health care providers might improve the health of MSM living with HIV by promoting access to ancillary services using strategies that increase patient awareness of how to obtain these services, especially among young, non-Hispanic black, and Hispanic/Latino MSM. PMID- 27657490 TI - Detection of Carbofuran-Protein Adducts in Serum of Occupationally Exposed Pesticide Factory Workers in Pakistan. AB - This study was conducted to investigate the protein adducts with pesticides in a cohort of 172 factory workers that were exposed to a mixture of pesticides. The 35 samples showing considerable variation in biochemical parameters, i.e., butyrylcholinestrase (BChE), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transferase (GGT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP/ALKP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK) enzymes, and controls were analyzed by reversed-phase nanoscale liquid chromatography tandem mass spectrometry (nLC-MS/MS) on an Orbitrap mass spectrometer employing a shotgun proteomics approach. Only protein adducts with carbofuran were found on serum proteins of these workers. These adducts were of carbofuran labeled lysine (Lys 142, Lys-183, Lys-287, and Lys-467), arginine (Arg-210, Arg-242, and Arg-256) from serum albumin, and serine (Ser-07, Ser-54, and Ser-150) from immunoglobulin proteins. The arginine residues (Arg-210, Arg-242, Arg-246, and Arg-434) from albumin were also found to be glycated in serum of workers showing a high level of glucose who also had glycated arginine (Arg-1120) modified with carbofuran in their tankyrase-1-binding protein. The number of tandem mass spectra of modified peptides increased with increasing time of exposure. This is the first report to demonstrate the presence of carbofuran-labeled albumin, immunoglobulin, and glycated arginine, which shows that lysine and arginine of human albumin and serine of immunoglobulin are covalently modified in the serum of workers that were occupationally exposed to carbofuran, and the modification is detectable by tandem mass spectrometry. These peptides modified with carbofuran can potentially be used as a biomarker of carbofuran exposure. PMID- 27657491 TI - Telemedicine for Retinopathy of Prematurity: An Evolving Paradigm. PMID- 27657492 TI - Beyond Risk Compensation: Clusters of Antiretroviral Treatment (ART) Users in Sexual Networks Can Modify the Impact of ART on HIV Incidence. AB - INTRODUCTION: Concerns about risk compensation-increased risk behaviours in response to a perception of reduced HIV transmission risk-after the initiation of ART have largely been dispelled in empirical studies, but other changes in sexual networking patterns may still modify the effects of ART on HIV incidence. METHODS: We developed an exploratory mathematical model of HIV transmission that incorporates the possibility of ART clusters, i.e. subsets of the sexual network in which the density of ART patients is much higher than in the rest of the network. Such clusters may emerge as a result of ART homophily-a tendency for ART patients to preferentially form and maintain relationships with other ART patients. We assessed whether ART clusters may affect the impact of ART on HIV incidence, and how the influence of this effect-modifying variable depends on contextual variables such as HIV prevalence, HIV serosorting, coverage of HIV testing and ART, and adherence to ART. RESULTS: ART homophily can modify the impact of ART on HIV incidence in both directions. In concentrated epidemics and generalized epidemics with moderate HIV prevalence (~ 10%), ART clusters can enhance the impact of ART on HIV incidence, especially when adherence to ART is poor. In hyperendemic settings (~ 35% HIV prevalence), ART clusters can reduce the impact of ART on HIV incidence when adherence to ART is high but few people living with HIV (PLWH) have been diagnosed. In all contexts, the effects of ART clusters on HIV epidemic dynamics are distinct from those of HIV serosorting. CONCLUSIONS: Depending on the programmatic and epidemiological context, ART clusters may enhance or reduce the impact of ART on HIV incidence, in contrast to serosorting, which always leads to a lower impact of ART on HIV incidence. ART homophily and the emergence of ART clusters should be measured empirically and incorporated into more refined models used to plan and evaluate ART programmes. PMID- 27657493 TI - MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma. AB - Importance: Current recommendations for patients with cirrhosis are to undergo surveillance for hepatocellular carcinoma (HCC) with ultrasonography (US) every 6 months. However, the sensitivity of US screening to detect early-stage HCC is suboptimal. Magnetic resonance imaging (MRI) with liver-specific contrast may detect additional HCCs missed by US in high-risk patients with cirrhosis. Objective: To compare the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC. Design, Setting, and Participants: A prospective surveillance study of 407 patients with cirrhosis and an estimated annual risk of HCC greater than 5% who underwent 1 to 3 biannual screening examinations with paired US and liver-specific contrast-enhanced MRI at a tertiary care hospital between November 2011 and August 2014. All patients were followed-up with dynamic computed tomography (CT) at 6 months after the study. The confirmation of HCC was based on the results of histologic examination and/or typical CT images of HCC. Main Outcomes and Measures: HCC detection rates and false-positive findings of US vs MRI. Results: A total of 407 eligible patients received 1100 screenings with paired US and MRI. Hepatocellular carcinomas were diagnosed in 43 patients: 1 detected by US only, 26 by MRI only, 11 by both, and 5 were missed by both. The HCC detection rate of MRI was 86.0% (37/43), significantly higher than the 27.9% (12/43) of US (P < .001). Magnetic resonance imaging showed a significantly lower rate of false-positive findings than US (3.0% vs 5.6%; P = .004). Of the 43 patients with HCC, 32 (74.4%) had very early stage HCC (a single nodule <2 cm), and 29 (67.4%) received curative treatments. The 3-year survival rate of the patients with HCC (86.0%) was not inferior to those without HCC (94.2%; hazard ratio, 2.26; 95% CI, 0.92-5.56; P = .08). Conclusions and Relevance: In patients with cirrhosis at high-risk of HCC, screening that used MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. With MRI screening, most of the cancers detected were at very early stage, which was associated with a high chance of curative treatments and favorable survival of patients. Whether surveillance with MRI would reduce mortality from HCC in high risk patients requires further investigation. Trial Registration: clinicaltrials.gov Identifier: NCT01446666. PMID- 27657494 TI - Diagnosis and Management of Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy. AB - Pregnancy-associated venous thromboembolism (PAVTE) consists of deep vein thrombosis and pulmonary embolism (PE) occurring during pregnancy or in the postpartum period. This condition is common and is a major source of morbidity in a population which is young and otherwise relatively healthy. Timely diagnosis and treatment are crucial in ensuring satisfactory patient outcomes. Diagnostic strategies for pregnancy-associated PE in particular require careful consideration of maternal and fetal risks. Low-molecular-weight heparins currently form the mainstay of treatment; however, there are uncertainties around optimal dosing of these agents in certain settings (e.g., obesity). This review discusses the diagnosis and suggested treatment of PAVTE. PMID- 27657495 TI - Hepatitis C Treatment and Barriers to Eradication. AB - Current treatment for chronic hepatitis C (CHC) is highly efficacious, well tolerated, and of short duration for the majority of patients. Despite the dramatic advances in therapy, there remain several barriers to disease eradication. These include deficiencies in screening, diagnosis, and access to care, and high cost of the direct-acting antiviral medications. In addition, incident cases and reinfection associated with injection drug use contribute to the persistent worldwide disease burden. This article will review the current CHC treatments, and outline the remaining gaps in therapy and barriers to disease eradication. PMID- 27657496 TI - Dispersal Ecology Informs Design of Large-Scale Wildlife Corridors. AB - Landscape connectivity describes how the movement of animals relates to landscape structure. The way in which movement among populations is affected by environmental conditions is important for predicting the effects of habitat fragmentation, and for defining conservation corridors. One approach has been to map resistance surfaces to characterize how environmental variables affect animal movement, and to use these surfaces to model connectivity. However, current connectivity modelling typically uses information on species location or habitat preference rather than movement, which unfortunately may not capture dispersal limitations. Here we emphasize the importance of implementing dispersal ecology into landscape connectivity, i.e., observing patterns of habitat selection by dispersers during different phases of new areas' colonization to infer habitat connectivity. Disperser animals undertake a complex sequence of movements concatenated over time and strictly dependent on species ecology. Using satellite telemetry, we investigated the movement ecology of 54 young male elk Cervus elaphus, which commonly disperse, to design a corridor network across the Northern Rocky Mountains. Winter residency period is often followed by a spring summer movement phase, when young elk migrate with mothers' groups to summering areas, and by a further dispersal bout performed alone to a novel summer area. After another summer residency phase, dispersers usually undertake a final autumnal movement to reach novel wintering areas. We used resource selection functions to identify winter and summer habitats selected by elk during residency phases. We then extracted movements undertaken during spring to move from winter to summer areas, and during autumn to move from summer to winter areas, and modelled them using step selection functions. We built friction surfaces, merged the different movement phases, and eventually mapped least-cost corridors. We showed an application of this tool by creating a scenario with movement predicted as there were no roads, and mapping highways' segments impeding elk connectivity. PMID- 27657498 TI - NDST1 Preferred Promoter Confirmation and Identification of Corresponding Transcriptional Inhibitors as Substrate Reduction Agents for Multiple Mucopolysaccharidosis Disorders. AB - The stepwise degradation of glycosaminoglycans (GAGs) is accomplished by twelve lysosomal enzymes. Deficiency in any of these enzymes will result in the accumulation of the intermediate substrates on the pathway to the complete turnover of GAGs. The accumulation of these undegraded substrates in almost any tissue is a hallmark of all Mucopolysaccharidoses (MPS). Present therapeutics based on enzyme replacement therapy and bone marrow transplantation have low effectiveness for the treatment of MPS with neurological complications since enzymes used in these therapies are unable to cross the blood brain barrier. Small molecule-based approaches are more promising in addressing neurological manifestations. In this report we identify a target for developing a substrate reduction therapy (SRT) for six MPS resulting from the abnormal degradation of heparan sulfate (HS). Using the minimal promoter of NDST1, one of the first modifying enzymes of HS precursors, we established a luciferase based reporter gene assay capable of identifying small molecules that could potentially reduce HS maturation and therefore lessen HS accumulation in certain MPS. From the screen of 1,200 compounds comprising the Prestwick Chemical library we identified SAHA, a histone deacetylase inhibitor, as the drug that produced the highest inhibitory effects in the reporter assay. More importantly SAHA treated fibroblasts expressed lower levels of endogenous NDST1 and accumulated less 35S GAGs in patient cells. Thus, by using our simple reporter gene assay we have demonstrated that by inhibiting the transcription of NDST1 with small molecules, identified by high throughput screening, we can also reduce the level of sulfated HS substrate in MPS patient cells, potentially leading to SRT. PMID- 27657497 TI - Vimentin, a Novel NF-kappaB Regulator, Is Required for Meningitic Escherichia coli K1-Induced Pathogen Invasion and PMN Transmigration across the Blood-Brain Barrier. AB - BACKGROUND: NF-kappaB activation, pathogen invasion, polymorphonuclear leukocytes (PMN) transmigration (PMNT) across the blood-brain barrier (BBB) are the pathogenic triad hallmark features of bacterial meningitis, but the mechanisms underlying these events remain largely unknown. Vimentin, which is a novel NF kappaB regulator, is the primary receptor for the major Escherichia coli K1 virulence factor IbeA that contributes to the pathogenesis of neonatal bacterial sepsis and meningitis (NSM). We have previously shown that IbeA-induced NF-kappaB signaling through its primary receptor vimentin as well as its co-receptor PTB associated splicing factor (PSF) is required for pathogen penetration and leukocyte transmigration across the BBB. This is the first in vivo study to demonstrate how vimentin and related factors contributed to the pathogenic triad of bacterial meningitis. METHODOLOGY/PRINCIPAL FINDINGS: The role of vimentin in IbeA+ E. coli K1-induced NF-kappaB activation, pathogen invasion, leukocyte transmigration across the BBB has now been demonstrated by using vimentin knockout (KO) mice. In the in vivo studies presented here, IbeA-induced NF-kappaB activation, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the BBB were significantly reduced in Vim-/- mice. Decreased neuronal injury in the hippocampal dentate gyrus was observed in Vim-/- mice with meningitis. The major inflammatory regulator alpha7 nAChR and several signaling molecules contributing to NF-kappaB activation (p65 and p-CamKII) were significantly reduced in the brain tissues of the Vim-/- mice with E. coli meningitis. Furthermore, Vim KO resulted in significant reduction in neuronal injury and in alpha7 nAChR-mediated calcium signaling. CONCLUSION/SIGNIFICANCE: Vimentin, a novel NF-kappaB regulator, plays a detrimental role in the host defense against meningitic infection by modulating the NF-kappaB signaling pathway to increase pathogen invasion, PMN recruitment, BBB permeability and neuronal inflammation. Our findings provide the first evidence for Vim-dependent mechanisms underlying the pathogenic triad of bacterial meningitis. PMID- 27657499 TI - Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury. AB - Blunt impact produces a heterogeneous brain injury in people and in animal models of traumatic brain injury. We report that a single closed head impact to adult C57/BL6 mice produced two injury syndromes (CHI-1 and CHI-2). CHI-1 mice spontaneously reinitiated breathing after injury while CHI-2 mice had prolonged apnea and regained breathing only after cardiopulmonary resuscitation and supplementation of 100% O2. The CHI-1 group significantly regained righting reflex more rapidly than the CHI-2 group. At 7 days post-injury, CHI-1, but not CHI-2 mice, acquired but had no long-term retention of an active place avoidance task. The behavioral deficits of CHI-1 and CHI-2 mice were retained one-month after the injury. CHI-1 mice had loss of hippocampal neurons and localized white matter injury at one month after injury. CHI-2 had a larger loss of hippocampal neurons and more widespread loss of myelin and axons. High-speed videos made during the injury were followed by assessment of breathing and righting reflex. These videos show that CHI-2 mice experienced a larger vertical g-force than CHI 1 mice. Time to regain righting reflex in CHI-2 mice significantly correlated with vertical g-force. Thus, physiological responses occurring immediately after injury can be valuable surrogate markers of subsequent behavioral and histological deficits. PMID- 27657500 TI - Multistep Intersystem Crossing Pathways in Cinnamate-Based UV-B Sunscreens. AB - The nonradiative decay pathways of jet-cooled para-methoxy methylcinnamate (p MMC) and para-methoxy ethylcinnamate (p-MEC) have been investigated by picosecond pump-probe and nanosecond UV-Deep UV pump-probe spectroscopy. The possible relaxation pathways were calculated by the (time-dependent) density functional theory. We found that p-MMC and p-MEC at low excess energy undergo multistep intersystem crossing (ISC) from the bright S1 (1pipi*) state to the lowest triplet T1 (3pipi*) state via two competing pathways through the T2 state in the time scale of 100 ps: (a) stepwise ISC followed after the internal conversion (IC) from S1 to the dark 1npi* state; (b) direct ISC from the S1 to T2 states. These picosecond multistep ISCs result in the torsion of C?C double bond by ~95 degrees in the T1 state, whose measured adiabatic energy and lifetime are 16577 cm-1 and ~20 ns, respectively, for p-MMC. These results suggest that the ISC processes play an indispensable role in the photoprotecting sunscreens in natural plants. PMID- 27657501 TI - Correction: HIF-2alpha Expression Regulates Sprout Formation into 3D Fibrin Matrices in Prolonged Hypoxia in Human Microvascular Endothelial Cells. AB - [This corrects the article DOI: 10.1371/journal.pone.0160700.]. PMID- 27657502 TI - Validity and Reliability of Ventilatory and Blood Lactate Thresholds in Well Trained Cyclists. AB - PURPOSE: The purpose of this study was to determine, i) the reliability of blood lactate and ventilatory-based thresholds, ii) the lactate threshold that corresponds with each ventilatory threshold (VT1 and VT2) and with maximal lactate steady state test (MLSS) as a proxy of cycling performance. METHODS: Fourteen aerobically-trained male cyclists ([Formula: see text] 62.1+/-4.6 ml.kg 1.min-1) performed two graded exercise tests (50 W warm-up followed by 25 W.min 1) to exhaustion. Blood lactate, [Formula: see text] and [Formula: see text] data were collected at every stage. Workloads at VT1 (rise in [Formula: see text];) and VT2 (rise in [Formula: see text]) were compared with workloads at lactate thresholds. Several continuous tests were needed to detect the MLSS workload. Agreement and differences among tests were assessed with ANOVA, ICC and Bland Altman. Reliability of each test was evaluated using ICC, CV and Bland-Altman plots. RESULTS: Workloads at lactate threshold (LT) and LT+2.0 mMol.L-1 matched the ones for VT1 and VT2, respectively (p = 0.147 and 0.539; r = 0.72 and 0.80; Bias = -13.6 and 2.8, respectively). Furthermore, workload at LT+0.5 mMol.L-1 coincided with MLSS workload (p = 0.449; r = 0.78; Bias = -4.5). Lactate threshold tests had high reliability (CV = 3.4-3.7%; r = 0.85-0.89; Bias = -2.1 3.0) except for DMAX method (CV = 10.3%; r = 0.57; Bias = 15.4). Ventilatory thresholds show high reliability (CV = 1.6%-3.5%; r = 0.90-0.96; Bias = -1.8-2.9) except for RER = 1 and V-Slope (CV = 5.0-6.4%; r = 0.79; Bias = -5.6-12.4). CONCLUSIONS: Lactate threshold tests can be a valid and reliable alternative to ventilatory thresholds to identify the workloads at the transition from aerobic to anaerobic metabolism. PMID- 27657503 TI - The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts. AB - Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity. PMID- 27657504 TI - Polypharmacy and Health-Related Quality of Life Among US Adults With Arthritis, Medical Expenditure Panel Survey, 2010-2012. AB - INTRODUCTION: Our objective was to determine the relationship between polypharmacy (treatment with prescription drugs from 6 or more drug classes concurrently) and health-related quality of life (HRQoL) among US adults with arthritis. METHODS: We conducted a retrospective cohort study that used 2-year longitudinal data from the Medical Expenditure Panel Survey to analyze a cohort of 6,132 adults aged over 21 years with arthritis. Measures of HRQoL were the summary scores from the mental component summary (MCS) and physical component summary (PCS) of the 12-item short-form health survey. Unadjusted and adjusted regression models were used to evaluate the association between polypharmacy and HRQoL measures. We used SAS, version 9.4, (SAS Institute Inc) to conduct all analyses. RESULTS: In unadjusted analyses, adults with arthritis taking prescription drugs from 6 or more drug classes concurrently had significantly lower MCS and PCS scores (beta, -3.11, P < .001 and beta, -10.26, P < .001, respectively) than adults taking prescription drugs from fewer than 6. After controlling for the demographic characteristics, number of mental and physical chronic conditions, and baseline MCS and PCS scores, adults taking prescription drugs from 6 or more drug classes concurrently had significantly lower PCS scores (beta, -1.68, P < .001), than those taking prescription drugs from fewer than 6. However, no significant difference in MCS scores was found between adults taking prescription drugs from 6 or more drug classes concurrently and those taking prescription drugs from fewer than 6 (beta, -0.27, P = .46). CONCLUSION: Polypharmacy is significantly associated with lower PCS scores among adults with arthritis. Because polypharmacy can lead to drug-drug and drug-disease interactions, health care providers need to consider the risk and adopt a cautious approach in prescribing multiple drugs to manage chronic conditions and in choosing therapies to improve HRQoL among adults with arthritis. PMID- 27657505 TI - A Tool for Assessing a Community's Capacity for Substance Abuse Care. AB - Evidence-based programs for prevention and intervention in substance abuse are increasing. Community needs assessments and health rankings provide descriptions of local behavioral health needs but do not provide public health practitioners and policy makers with guidelines on the number of programs, health care practitioners, or interventions needed in the local substance abuse care system. This article presents a new framework for measuring and assessing the substance abuse care system in a community. The assessment can inform resource allocation across the continuum of care to more equitably and efficiently distribute interventions and care. We conducted 2 literature reviews and synthesized our findings to create a community assessment methodology and needs calculator, CAST (calculating for an adequate system tool). We reviewed 212 articles to produce an inventory of community and social correlates of behavioral health, components of a substance abuse care system, and numerical values for guidelines for estimating community needs. CAST produces community-specific assessments of the capacity of the components of a community substance abuse care system. CAST generates recommendations by the application of social and community determinants of health as risk coefficients to each estimate of component need. CAST can assist public health practitioners in evaluation and improvement of the capacity of community based, substance abuse care systems. By using recommendations for component needs across the continuum of care, community leaders can use CAST to prioritize resource allocation more effectively and efficiently. PMID- 27657507 TI - Walking to Work: Trends in the United States, 2005-2014. AB - I examined trends from 2005 through 2014 in walking to work compared with other modes of travel. For each year, I calculated the percentage of travel to work by private vehicle, public transportation, and walking and used distance decay functions to analyze the distribution of walking by distance. I found that the percentage of travel to work by walking remained stable, with a slight increase over time, and that people tended to walk longer to get to work. The trend is positive and encouraging, although more evidence is needed to confirm my findings. PMID- 27657506 TI - Ever-Use and Curiosity About Cigarettes, Cigars, Smokeless Tobacco, and Electronic Cigarettes Among US Middle and High School Students, 2012-2014. AB - INTRODUCTION: Among young people, curiosity about tobacco products is a primary reason for tobacco experimentation and is a risk factor for future use. We examined whether curiosity about and ever-use of tobacco products among US middle and high school students changed from 2012 to 2014. METHODS: Data came from the 2012 and 2014 National Youth Tobacco Surveys, nationally representative surveys of US students in grades 6 through 12. For cigarettes, cigars, smokeless tobacco, and e-cigarettes (2014 only), students were classified as ever-users or never users of each product. Among never-users, curiosity about using each product was assessed by asking participants if they had "definitely," "probably," "probably not," or "definitely not" been curious about using the product. RESULTS: From 2012 to 2014, there were declines in ever-use of cigarettes (26% to 22%; P = .005) and cigars (21% to 18%; P = .003) overall and among students who were Hispanic (cigarettes, P = .001; cigars, P = .001) or black (cigarettes, P = .004; cigars, P = .01). The proportion of never-users reporting they were "definitely not" curious increased for cigarettes (51% to 54%; P = .01) and cigars (60% to 63%; P = .03). Ever-use and curiosity about smokeless tobacco did not change significantly from 2012 to 2014. In 2014, the proportion of young people who were "definitely" or "probably" curious never-users of each product was as follows: cigarettes, 11.4%; e-cigarettes, 10.8%; cigars, 10.3%; and smokeless tobacco, 4.4%. CONCLUSION: The proportion of US students who are never users and are not curious about cigarettes and cigars increased. However, many young people remain curious about tobacco products, including e-cigarettes. Understanding factors driving curiosity can inform tobacco use prevention for youth. PMID- 27657509 TI - Frailty syndrome in an independent urban population in Brazil (FIBRA study): a cross-sectional populational study. AB - CONTEXT AND OBJECTIVE:: Frailty is a multifactorial syndrome. The aim of this study was to determine the prevalence and characteristics of frailty syndrome in an elderly urban population. DESIGN AND SETTING:: Cross-sectional study carried out at the homes of a randomized sample representing the independent elderly individuals of Ribeirao Preto, Brazil. METHODS:: Sociodemographic characteristics, clinical data and criteria of the frailty phenotype were obtained at the subjects' homes; 385 individuals were evaluated. Frailty was defined based on detection of weight loss, exhaustion, weakness, slowness and low physical activity level. Individuals with three or more of these characteristics were classified as frail and those with one or two as pre-frail. Specific cutoff points for weakness, slowness and low physical activity level were calculated. RESULTS:: The participants' mean age was 73.9 +/- 6.5 years, and 64.7% were women. 12.5% had lost weight over the last year; 20.5% showed exhaustion, 17.1% slowness, 24.4% low physical activity level and 20.5% weakness. 9.1% were considered frail and 49.6% pre-frail. Frail subjects were older, attended more medical visits, had a higher chance of hospitalization within the last 12 months and had more cerebrovascular events, diabetes, neoplasms, osteoporosis and urinary and fecal incontinence. CONCLUSION:: In this independent elderly population, there were numerous frail and pre-frail individuals. Frailty syndrome was associated with high morbidity. Cutoff points for weakness, slowness and low physical activity level should be adjusted for the population under study. It is essential to identify frail and pre-frail older individuals for appropriate interventions. PMID- 27657508 TI - Intrinsic Disorder of the C-Terminal Domain of Drosophila Methoprene-Tolerant Protein. AB - Methoprene tolerant protein (Met) has recently been confirmed as the long-sought juvenile hormone (JH) receptor. This protein plays a significant role in the cross-talk of the 20-hydroxyecdysone (20E) and JH signalling pathways, which are important for control of insect development and maturation. Met belongs to the basic helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) family of transcription factors. In these proteins, bHLH domains are typically responsible for DNA binding and dimerization, whereas the PAS domains are crucial for the choice of dimerization partner and the specificity of target gene activation. The C-terminal region is usually responsible for the regulation of protein complex activity. The sequence of the Met C-terminal region (MetC) is not homologous to any sequence deposited in the Protein Data Bank (PDB) and has not been structurally characterized to date. In this study, we show that the MetC exhibits properties typical for an intrinsically disordered protein (IDP). The final averaged structure obtained with small angle X-ray scattering (SAXS) experiments indicates that intrinsically disordered MetC exists in an extended conformation. This extended shape and the long unfolded regions characterise proteins with high flexibility and dynamics. Therefore, we suggest that the multiplicity of conformations adopted by the disordered MetC is crucial for its activity as a biological switch modulating the cross-talk of different signalling pathways in insects. PMID- 27657510 TI - Gamma-glutamyl transferase and pulmonary embolism. PMID- 27657511 TI - A rare association of intussusception and celiac disease in a child. AB - CONTEXT:: Intussusception is a common cause of acute intestinal obstruction in the pediatric population and it is normally idiopathic. Rare cases of chronic intussusception require investigation with greater attention. CASE REPORT:: We present a clinical case of a three-year-old boy with aqueous diarrhea, abdominal distension, vomiting and weight loss over a two-month period. During the investigation, abdominal ultrasound showed imaging of intussusception. The intraoperative findings showed the intussusception had resolved spontaneously. In further investigation, it was found that the diarrhea was malabsorptive and, after the patient underwent upper gastrointestinal endoscopy, a diagnosis of celiac disease was made. After a gluten-free diet was introduced, the patient showed complete remission of symptoms and regained weight, and normal growth was reestablished. CONCLUSION:: If the clinical presentation of intussusception is unusual, etiological investigation should be undertaken. In this case report, celiac disease was the underlying cause. PMID- 27657512 TI - Organocatalytic Enantioselective Allylic Etherification of Morita-Baylis-Hillman Carbonates and Silanols. AB - The organocatalytic asymmetric allylic etherification reaction of Morita-Baylis Hillman carbonates and silanols was reported for the first time. With modified cinchona alkaloid (DHQD)2PYR as the catalyst, a series of aromatic, heterocyclic, or aliphatic Morita-Baylis-Hillman carbonates (25 examples) worked well with triphenylsilanol, affording the corresponding products in moderate to good yields (up to 98%), high regioselectivities (>20:1), and good enantioselectivities (up to 92%). When dimethylphenylsilanol was used as the nucleophile, the product was obtained in 60% yield and 87% ee. PMID- 27657513 TI - Three-Dimensional Analysis of Cell Division Orientation in Epidermal Basal Layer Using Intravital Two-Photon Microscopy. AB - Epidermal structures are different among body sites, and proliferative keratinocytes in the epidermis play an important role in the maintenance of the epidermal structures. In recent years, intravital skin imaging has been used in mammalian skin research for the investigation of cell behaviors, but most of these experiments were performed with rodent ears. Here, we established a non invasive intravital imaging approach for dorsal, ear, hind paw, or tail skin using R26H2BEGFP hairless mice. Using four-dimensional (x, y, z, and time) imaging, we successfully visualized mitotic cell division in epidermal basal cells. A comparison of cell division orientation relative to the basement membrane in each body site revealed that most divisions in dorsal and ear epidermis occurred in parallel, whereas the cell divisions in hind paw and tail epidermis occurred both in parallel and oblique orientations. Based on the quantitative analysis of the four-dimensional images, we showed that the epidermal thickness correlated with the basal cell density and the rate of the oblique divisions. PMID- 27657514 TI - Effect of montelukast on markers of airway remodeling in children with asthma. AB - BACKGROUND: Asthma is a pathology characterized by chronic inflammation and remodeling of the airways. OBJECTIVES: To evaluate the effect of montelukast treatment on markers of airway inflammation and remodeling in children with mild asthma and to evaluate if the administration of montelukast to children with mild asthma could inhibit the release of matrix metallopeptidase 9, matrix metallopeptidase 12, tissue inhibitor of metalloproteinase 1, transforming growth factor beta 1, C-peptide terminal procollagen type (PICP), and eosinophils count, which are markers of inflammation and remodeling in induced sputum. METHODS: Thirty children with mild asthma were recruited. They were randomized into two groups: group A received montelukast and as needed beta-2-agonist for 8 weeks (T0 T1), whereas group B received placebo and as needed beta-2-agonist for 8 weeks. After 2 weeks of washout (T1-T2), they were reallocated for treatment according a crossover design (T2-T3). Tests for lung function, oral exhaled nitric oxide, and hypertonic saline solution-induced sputum level were performed at T0-T1-T2-T3. RESULTS: In the placebo group, the PICP mean (standard deviation [SD]) value at baseline was 2279.42 +/- 2530.77 pg/mL and 1916.00 +/- 2178.75 pg/mL after treatment. Patients treated with montelukast, in contrast, showed a baseline mean (SD) value of 2439.29 +/- 2834.51 pg/mL and 1406.72 +/- 1508.65 pg/mL after treatment. The difference between the mean pre- and posttreatment decrease of PICP in the two groups was statistically significant (delta -690.21 pg/mL [95% confidence interval, -1220.83 to -159.5844 pg/mL]; p = 0.011). The mean (SD) percentage of the eosinophil count in the placebo group was 3.11 +/- 4.03% at baseline and 4.86 +/- 5.83% after treatment. Patients treated with montelukast, in contrast, showed a percentage mean (SD) value at baseline of 4.51 +/- 5.48% and, after treatment, of 3.06 +/- 3.29%. The difference between the mean pre- and posttreatment decrease of the percentage eosinophil count in the two groups was statistically significant (delta -2.76% [95% confidence interval, -4.65 to 0.87%]; p = 0.004). CONCLUSION: This study investigated in vivo effects of montelukast on remodeling markers. The reduction of PICP levels and eosinophil count supported the hypothesis that montelukast can modulate collagen deposition in airways and reduce eosinophilic airway inflammation. Clinical Trials database clinicaltrials.gov (NCT00875082). PMID- 27657515 TI - Serum tryptase level and inflammatory markers in exhaled breath condensate of children with exercise-induced symptoms. AB - BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction (EIB) is poorly understood. OBJECTIVE: To evaluate the biomarkers concentration in exhaled breath condensate (EBC) in schoolchildren with postexercise symptoms. We also evaluated changes in fractional exhaled nitric oxide (FeNO) value and the serum tryptase level after exercise. METHODS: One hundred children with postexercise symptoms were included. Methacholine challenge testing (MCT) was performed at visit 2, and exercise challenge testing (ECT) was performed at visit 3. Before and after ECT serum tryptase levels and FeNO values were measured. EBC was collected after ECT from 10 randomly selected children from each group. The children were assigned to the following groups: ECT(+) MCT(+), ECT(+) MCT(-), ECT(-) MCT(+), ECT(-) MC(-). We measured the following molecules: eotaxin, interleukin (IL) 8, IL-1ra, IL-1 beta, IL-6, IL-1 alpha, IL-12(p40), IL-5, granulocyte-macrophage colony-stimulating factor, IL-7, IL-15, IL-4, IL-2, IL-10, tumor necrosis factor alpha, interferon gamma, IL-13, tumor necrosis factor beta, monocyte chemoattractant protein-1, IL-17A, macrophage inflammatory proteins-1 alpha, macrophage inflammatory proteins-1 beta, IL-12(p70), and regulated on activation, normal T-cell expressed and secreted by using a multiplex immunoassay. Prostaglandin E2 (PGE2), leukotriene B4, and cysteinyl leukotriene were analyzed by using separate enzyme-linked immunosorbent assay kits. RESULTS: In the MCT(+) group, a detectable level of IL4 in EBC and detectible levels of eicosanoids were seen in the ECT(+) group. We observed the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations in patients with detectable compared with patients without detectable levels of cytokines in EBC. We showed ECT-induced reduction in the tryptase level in patients with a nondetectable PGE2 level in EBC and an increase in tryptase levels in patients who had detectable levels of PGE2 in EBC. CONCLUSIONS: EBC was a useful method to estimate inflammation but only in children with symptoms and with EIB shown by a positive ECT. Children with a positive ECT had detectable levels of eicosanoids in EBC; the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations was observed. The results of above study confirm the role of mast cells and eicosanoids in the pathogenesis of EIB in children. PMID- 27657516 TI - Comparison of pain during skin-prick testing, immunizations, and phlebotomy. AB - BACKGROUND: Allergy skin prick testing is a medical procedure that is very useful for assessing a patient's sensitization to specific allergens. Some patients are worried about pain associated with prick skin testing. OBJECTIVE: To compare pain among different age groups, to look at pain during skin prick testing in younger children, and to compare the pain during skin prick testing to procedures including routine immunizations and phlebotomy. METHODS: A survey was provided to patients undergoing allergy skin testing, immunizations or phlebotomy at the Wilford Hall Medical Center. RESULTS: There were 197 patients and 26 parents of patients aged 3-8 years who completed surveys during allergy skin testing. The average anticipated (pre procedure) pain score was 4.3 for the patients aged 3-8 years, 4.6 for the patients aged 9-17 years and 3.2 for the patients older than 17 years. The average actual pain score of the patients during skin testing was 3.1 for the patients aged 3-8 years, 2.2 for the patients aged 9-17 years and 1.4 for the patients older than 17 years. For the parents of patients aged 3-8 years, the average anticipated average pain score was 3.0 and the average actual pain score was 1.7. CONCLUSIONS: The actual pain experienced from skin prick testing is perceived to be much less than the anticipated pain. Patients and referring physicians should not have a fear of pain from allergy skin prick testing. PMID- 27657517 TI - Health care resource use and associated costs among patients with seasonal versus perennial allergic rhinitis. AB - BACKGROUND: Health care resource use (HRU) and costs among patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) have not been widely studied. OBJECTIVE: To develop an algorithm to classify patients with SAR and patients with PAR, and to evaluate treatment patterns, HRU, and costs among these patients. METHODS: Patients with allergic rhinitis (AR) were identified retrospectively by using electronic medical records and administrative claims data, with an index date as the earlier of the date of AR diagnosis or allergy medication use. Patients with AR were followed-up from 12 months before the index date through 12 months after the index date (follow-up) and were classified as SAR or PAR based on medication patterns during follow-up. AR-related HRU, allergy immunotherapy administration, and costs per patient per year during follow-up were compared between patients with SAR and those with PAR, with analyses stratified by asthma diagnosis before the index date and by physician specialty (primary care physician versus specialist). RESULTS: Approximately 23% of patients with AR were classified as having PAR and 77% as having SAR. During follow-up, the patients with PAR had more allergy medication prescriptions versus the patients with SAR (8.0 versus 2.4 prescriptions), higher prescription medication costs ($1551 versus $313), higher allergy immunotherapy cost ($180 versus. $118), and higher total AR-related costs ($1944 versus $643); all with p < 0.001. Patients with asthma had higher costs than those without asthma. Patients seen by a specialist has higher costs than those treated by a primary care physician. CONCLUSION: Patients with PAR experienced more AR-related prescription drug use and higher health care costs than patients with SAR, with prescription drug costs being the main cost driver. Treatments that reduce the need for ongoing prescription medication use have the potential to be cost saving. PMID- 27657518 TI - American Academy of Allergy, Asthma & Immunology membership experience with allergen immunotherapy safety in patients with specific medical conditions. AB - BACKGROUND: Little data in the literature exist concerning patients with certain underlying medical conditions who receive allergen subcutaneous immunotherapy (SCIT). OBJECTIVE: To survey allergists' experience with SCIT in patients with medical conditions considered to impose an elevated risk for untoward outcomes. METHODS: A Web-based survey was conducted among members of the American Academy of Allergy, Asthma & Immunology to query about their experience with SCIT in patients with certain medical conditions. RESULTS: There were 1085 replies (21% response), of whom, 86% were U.S. based, 51% were suburban, 31% were academic, 42% were medium-sized practices, and 54% had >15 years' experience. In responders' opinion, SCIT was "contraindicated" in patients with the following: acquired immune deficiency syndrome (AIDS) (48%), cancer (and still receiving active treatment) (33%), severe asthma (32%), and a history of transplantation (30%). Even so, survey responders collectively gave SCIT to >2400 patients for each of these conditions: severe asthma, coronary artery disease, cancer in remission, and autoimmune disorders; and to >=5400 patients with hypertension and >=4100 women who became pregnant. The experience of colleagues with these patients rarely resulted in major problems (i.e., activation of underlying disease, systemic reactions to SCIT, or SCIT discontinuation), with the exception of severe asthma (12.5%), initiation of SCIT during pregnancy (5.4%), and AIDS (4.2%). For most other conditions, it was <=1.5% (e.g., continue during pregnancy, cancer in remission, history of transplantation, positive human immunodeficiency virus and no AIDS). CONCLUSION: According to the experience of a large group of practicing allergists, the American Academy of Allergy, Asthma & Immunology members, few medical conditions seemed to pose an elevated risk for untoward outcomes from SCIT. Because these are survey results, prospective research might yield even more solid data. PMID- 27657519 TI - Relievers, controllers, and inhaler technique: A physician-patient challenge. PMID- 27657520 TI - Albuterol multidose dry powder inhaler and albuterol hydrofluoroalkane versus placebo in children with persistent asthma. AB - BACKGROUND: Many children struggle with albuterol hydrofluoroalkane (HFA) inhalers. Albuterol multidose dry powder inhaler (MDPI) may simplify rescue bronchodilator use in children. OBJECTIVE: To demonstrate the comparability of albuterol MDPI and albuterol HFA in children with asthma. METHODS: This phase II, multicenter, double-blind, double-dummy, single-dose, five-period, crossover study randomized patients (ages 4-11 years) with persistent asthma and prestudy forced expiratory volume in 1 second (FEV1) of 60-90% of predicted to 1 of 10 treatment sequences that contained albuterol MDPI (90 and 180 MUg), albuterol HFA (90 and 180 MUg), and placebo MDPI and placebo HFA. Efficacy was evaluated by measuring the area under the baseline-adjusted percent-predicted FEV1-time curve over 6 hours (PPFEV1 AUC0-6) after dosing. Safety was evaluated by adverse events. RESULTS: The full analysis set included 61 patients. Albuterol MDPI and albuterol HFA significantly improved PPFEV1 AUC0-6 versus placebo (p <= 0.0107). Mean improvement (+/- standard error [SE]) in PPFEV1 AUC0-6 versus placebo with albuterol MDPI at 90 and 180 MUg was similar (21.2 +/- 4.87 [95% confidence interval {CI}, 11.60-30.81], and 22.6 +/- 4.87 [95% CI, 13.00-32.20], %.hour, respectively). Mean improvement (+/- SE) with albuterol HFA 180 MUg was significantly (p = 0.0226) greater versus albuterol HFA 90 MUg (23.7 +/- 4.85 [95% CI, 14.13-33.23], and 12.5 +/- 4.85 [95% CI, 2.93-22.05], %.hour, respectively). All doses of albuterol were well tolerated. CONCLUSION: Albuterol MDPI 90 and 180 MUg and albuterol HFA 180 MUg provided similar and significant FEV1 improvements versus placebo; albuterol HFA 90 MUg was significant versus placebo but seemed less effective based on absolute improvements in FEV1. ClinicalTrials.gov identifier: NCT01899144. PMID- 27657521 TI - MP-AzeFlu provides rapid and effective allergic rhinitis control in real life: A pan-European study. AB - BACKGROUND: The European Union has prioritized allergic rhinitis (AR) control. Contre les Maladies Chronique pour un Vieillissement Actif Allergic Rhinitis and its Impact on Asthma has endorsed the visual analog scale (VAS) as the AR control language and incorporated it into a new AR treatment algorithm. Concurrently, the Respiratory Effectiveness Group and the European Academy of Allergy and Clinical Immunology are striving to improve the quality of published real-life AR research. Our aim was to assess the effectiveness of MP-AzeFlu by using a VAS in a well-designed, real-life, pan-European study. METHODS: A total of 2988 patients (aged >= 12 years) with Allergic Rhinitis and its Impact on Asthma defined moderate-to-severe AR from Germany, Sweden, Romania, United Kingdom, Denmark, and Norway were included. Patients (except from the United Kingdom) assessed symptom severity by using a VAS from 0 mm (not at all bothersome) to 100 mm (very bothersome) on days 0, 1, 3, 7, and the last visit (~day 14) in the morning before MP-AzeFlu use. Patients' perceived level of disease control was assessed on day 3. A VAS score cutoff on day 3 for "well controlled" was determined, and the proportion of patients who achieved this response was calculated. RESULTS: MP AzeFlu was associated with a mean VAS score reduction from 73.7 mm at baseline to 23.4 mm by the last visit. This reduction was significant (p < 0.001) compared with baseline from day 1 and sustained until the last day of the study. By day 3, 50.3% of patients considered their symptoms well controlled; 18.2, 40.0, 66.6, and 75.9% of the patients achieved the <=38 mm well-controlled VAS score cutoff on days 1, 3, 7 and the last day, respectively. The results were consistent across countries, age, phenotype, and severity. CONCLUSION: MP-AzeFlu provided effective and rapid symptom control in a real-life pan-European setting and aligned with the European Union, Contre les Maladies Chronique pour un Vieillissement Actif Allergic Rhinitis and its Impact on Asthma, the Respiratory Effectiveness Group, and the European Academy of Allergy and Clinical Immunology objectives, supporting MP-AzeFlu as the drug of choice for the treatment of moderate-to-severe AR. PMID- 27657523 TI - The clinical and laboratory characteristics of acute spontaneous urticaria and its progression to chronic spontaneous urticaria. AB - BACKGROUND: The natural history of the progression from acute spontaneous urticaria (ASU) to chronic spontaneous urticaria (CSU), CSU remains poorly understood. OBJECTIVE: To identify clinical and laboratory patient attributes that may be predictive of ASU progression to CSU. METHODS: We prospectively studied consecutive adult patients (age >= 18 years) with a diagnosis of urticaria of <6 weeks' duration. Healthy age- and sex-matched subjects served as controls. At study entry, autologous serum skin test (ASST), complete blood cell count, erythrocyte sedimentation rate, thyroid function tests, antinuclear antibodies, antithyroglobulin and antiperoxidase antibodies, and immunoglobulin E level were assessed in all the subjects. ASST and urticaria activity score assessment were performed in all the patients at baseline and then at weeks 7, 12, 24, and 48. RESULTS: Of 114 patients with acute urticaria and without identifiable causes, 73 patients (64%) were included in the ASU group, 41 patients in the CSU group (36%), and 44 healthy subjects in the control group. At baseline, 26 patients in the CSU group (63.4%) had a positive ASST result, whereas only 17 patients with a positive ASST result (23.3%) were revealed in the ASU group (p < 0.001). Patients with baseline ASST positive results were characterized by more profound basopenia (mean [standard deviation], 0.05 +/- 0.08 cell/mm(3)) and more anti-thyroid peroxidase antibodies (18 [41.8%]) than those with the negative baseline ASST result (mean [standard deviation], 0.13 +/- 0.09 cell/mm(3), p < 0.001 more profound basopenia; and 13 (18.1%), p = 0.009 more thyroid peroxidase antibodies). We observed the disappearance of ASST positive result in some patients with CSU with baseline positive ASST results, whereas, in some subjects with CSU, baseline negative ASST results came to be positive results throughout the study period. A baseline positive ASST result of patients with ASU was a significant determinant (odds ratio 5.91 [95% confidence interval, 2.57-13.62]; p < 0.001) for a CSU diagnosis at week 7. CONCLUSION: The patients with ASU who progressed toward CSU were characterized by a positive ASST result, thyroid autoimmunity, and profound basopenia at baseline. PMID- 27657522 TI - Assessment of anti-inflammatory effect from addition of a long-acting beta-2 agonist to inhaled corticosteroid. AB - BACKGROUND: Inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) are thought to enhance the pharmacologic action of one another by a synergistic effect. OBJECTIVE: We compared a group of patients who used ICS monotherapy with a group treated with ICS/LABA combination and evaluated the LABAs with regard to the synergistic effect on the anti-inflammatory action of the ICS. METHODS: This study was conducted with 107 adult patients with mild-to-moderate bronchial asthma. The patients were randomly assigned to either ICS monotherapy (n = 55) or an ICS/LABA combination (n = 52). Both groups were assessed for respiratory function, fractional exhaled nitric oxide, induced sputum, and airway hyperresponsiveness before and after 6 months of treatment. RESULTS: The ICS/LABA combination group showed significantly greater improvement than the ICS monotherapy group in the forced expiratory volume in 1 second/forced vital capacity (p < 0.01), forced expiratory volume in 1 second % predicted (p < 0.05), % predicted maximal expiratory flow at 50% (p < 0.01), % predicted maximal expiratory flow at 25% (p < 0.05), and airway hyperresponsiveness (p < 0.01). However, the two groups did not show significant differences in changes in the fractional exhaled nitric oxide (p = 0.47) or the percentage of eosinophils in the central (p = 0.85) or peripheral sputum (p = 0.98). CONCLUSION: The significant improvement in respiratory function in the ICS/LABA combination treatment group compared with the ICS monotherapy group indicated an additive bronchodilator effect of the LABA. However, the two groups did not differ in airway inflammation, which indicated that a synergistic effect of the LABA on enhancing the anti-inflammatory action of the ICS was not clinically apparent. PMID- 27657524 TI - Safety profile of oral immunotherapy with cow's milk and hen egg: A 10-year experience in controlled trials. AB - BACKGROUND: Oral immunotherapy (OIT) for food allergy is gaining interest due to the favorable clinical results reported with cow's milk, hen egg and peanut. The safety of the procedure remains a critical aspect that can limit the introduction of OIT in clinical practice. OBJECTIVE: We described herein, in detail, the occurrence and characteristics of adverse events (AE) with OIT in children who participated in controlled trials at our unit. METHODS: The clinical records of 68 children who received active treatment (40 for cow's milk and 28 for hen egg) were carefully reviewed. The inclusion and exclusion criteria, and the grading of AEs were the same across the trials. Of the 68 children involved, 6 (9%) had to discontinue the OIT procedure due to severe AEs. Fifty percent of the children underwent the buildup and maintenance phases without AEs. Mild-to-moderate AEs were documented in 28 patients, who could complete the desensitization. The majority of reactions were mild or moderate, occurred during an acute intercurrent illness and required only symptomatic treatment. CONCLUSION: A careful review of the patients who received food OIT in controlled trials confirmed that AEs were not rare but that ~90% of children could achieve an effective desensitization. The procedure remains investigational and should be performed only by trained physicians, especially in the pediatric setting. PMID- 27657525 TI - Effect of educational and electronic medical record interventions on food allergy management. AB - BACKGROUND: The growing prevalence of food allergies indicates a responsibility among primary care providers to ensure that their patients receive accurate diagnosis and management. OBJECTIVE: To improve physician knowledge and management of food allergies by implementing educational and electronic medical record interventions. METHODS: Pre- and posttest scores of pediatric residents and faculty were analyzed to assess the effectiveness of an educational session designed to improve knowledge of food allergy management. One year later, a best practice advisory was implemented in the electronic medical record to alert providers to consider allergy referral whenever a diagnosis code for food allergy or epinephrine autoinjector prescription was entered. A review of charts 6 months before and 6 months after each intervention was completed to determine the impact of both interventions. Outcome measurements included referrals to an allergy clinic, prescription of self-injectable epinephrine, and documentation that written emergency action plans were provided. RESULTS: There was a significant increase in test scores immediately after the educational intervention (mean, 56.2 versus 84.3%; p < 0.001). Posttest scores remained significantly higher than preintervention scores 6 months later (mean score, 68.0 versus 56.2%; p = 0.006). Although knowledge improved, there was no significant difference in the percentage of patients who were provided allergy referral, were prescribed an epinephrine autoinjector, or were given an emergency action plan before and after both interventions. CONCLUSION: Neither intervention resulted in improvements in the management of children with food allergies at our pediatrics clinic. Further studies are needed to identify effective strategies to improve management of food allergies by primary care physicians. PMID- 27657526 TI - Anxiety and depression in adults with primary immunodeficiency: How much do these patients experience and how much do they attribute to their primary immunodeficiency? AB - INTRODUCTION: Primary immunodeficiency (PID) is a rare group of disorders that manifest similarly with infection, neoplasms, allergic, and autoimmune diseases, and are treated with injectable medications. Often the burden of disease and cost of management is excessive, and premature death is not uncommon. In light of these features of PID, it was our objective to survey our cohort to assess for factors that can influence depression and anxiety. METHODS: We used an investigator-developed survey, in addition to the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale, after institutional review board approval of our pilot study, to determine the extent of anxiety and depression that our patients with PID experienced and variables that may have affected the difference of expression. The differences among groups were tested by using Wilcoxon rank sum tests, Kruskal-Wallis tests, and chi-square tests. RESULTS: The patients with PID had similar depression compared with the U.S. population, as assessed by the HAM-D scale. Risk factors associated with elevated HAM-D scores included the following: not driving, intravenous immunoglobulin therapy (versus subcutaneous), nurse-administered therapy (versus self administered), having unpleasant adverse effects from therapy, previously attempted suicide, and family members with reported anxiety and/or depression. Anxiety was not significantly increased in our cohort. Risk factors for significantly elevated Hamilton Anxiety Rating Scale scores included the following: having poor health, an unhealthy diet, lack of refreshing sleep, and family members with reported anxiety and/or depression. CONCLUSION: Many factors influence depression and anxiety, and may add to the morbidity of PID. Patients should be assessed for our identified factors for depression and anxiety. Treatment or referrals should be initiated as it is hoped to improve our patients' quality of life and outcomes. PMID- 27657527 TI - For the Patient. PMID- 27657528 TI - The Water Load Test As a Measure of Gastric Interoception: Development of a Two Stage Protocol and Application to a Healthy Female Population. AB - The sensitivity for one's own internal body signals (i.e., interoception) has been demonstrated to play an important role in the pathogenesis of eating and weight disorders. Most previous measures assessing interoceptive processing have not, or only partly, captured perception of hunger and satiety cues, which is a core aspect of interoceptive deficits in eating disorders. In addition, methods used to measure sensitivity to gastric signals are heterogeneous and findings inconsistent. The primary aim of the present study was to establish a standardised test to measure gastric interoception, and to provide normative data using a non-clinical adult sample. The two-step Water Load Test (WLT-II) involves ingestion of non-caloric water until perceived satiation (step 1) and until maximum fullness (step 2). The WLT-II consists of several variables: Besides volumes of water ingested until satiation and maximum fullness expressed in ml, percentage of satiation to maximum fullness is calculated as an individual index of gastric interoception that is not confounded with stomach capacity. Ninety nine healthy women participated in the study. Measures included the WLT-II, the heartbeat tracking test, a self-report questionnaire assessing subjective sensations, and the Eating Disorder Inventory-2. Twenty-eight participants underwent test-retest of the WLT-II. Results suggest that the WLT-II is a valid and reliable measure of gastric interoception. Importantly, satiation volume and percentage of satiation to maximum fullness were strongly positively related to self-reported bulimic symptoms, indicating that the WLT-II could emerge as a useful clinical tool to measure interoceptive processing in the field of eating disorders. PMID- 27657529 TI - Rapid On-Site Evaluation Does Not Improve Endoscopic Ultrasound-Guided Fine Needle Aspiration Adequacy in Pancreatic Masses: A Meta-Analysis and Systematic Review. AB - BACKGROUND AND OBJECTIVES: Rapid on-site evaluation (ROSE) during endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of pancreatic masses has been reported to be associated with improved adequacy and diagnostic yield. However, recent observational data on the impact of ROSE have reported conflicting results. A meta-analysis and systematic review was therefore conducted to evaluate the contribution of ROSE during EUS-FNA of pancreatic masses. METHOD: A systematic search was conducted in MEDLINE/Pubmed and EMBASE databases for studies comparing the efficacy of ROSE between patients in two cohorts. Outcomes considered included diagnostic adequate rate, diagnostic yield, number of needle passes, pooled sensitivity and specificity. Findings from a random-effects model were expressed as pooled risk difference (RD) with 95% confidence intervals (CIs). RESULTS: A total of 7 studies (1299 patients) was finally included and further analyzed in the current meta-analysis. EUS-FNA with ROSE could not improve diagnostic adequacy (RD = 0.05, 95% CI: -0.01-0.11) and diagnostic yield (RD = 0.04 95%CI: -0.05, 0.13). The number of needle passes showed no statistically significant difference with and without ROSE (RD = -0.68 95%CI: -2.35, 0.98). The pooled sensitivity and specificity of ROSE group were 0.91 (95%CI: 0.87, 0.94) and 1 (95%CI: 0.94, 1.00). The pooled sensitivity and specificity of non-ROSE group were 0.85 (95%CI: 0.80, 0.89) and 1 (95%CI: 0.95, 1.00). ROSE group and non-ROSE group showed comparable sensitivity and specificity. CONCLUSION: Compared to historical reports of its clinical efficacy in patients with pancreatic lesions, ROSE may be not associated with an improvement of diagnostic yield, adequate rate, pooled sensitivity and specificity. PMID- 27657530 TI - Serogroup-Specific Characteristics of Localized Meningococcal Meningitis Epidemics in Niger 2002-2012 and 2015: Analysis of Health Center Level Surveillance Data. AB - To compare dynamics of localized meningitis epidemics (LE) by meningococcal (Nm) serogroup, we analyzed a surveillance database of suspected and laboratory confirmed Nm cases from 373 health areas (HA) of three regions in Niger during 2002-2012 and one region concerned by NmC epidemics during 2015. We defined LE as HA weekly incidence rates of >=20 suspected cases per 100,000 during >=2 weeks and assigned the predominant serogroup based on polymerase chain reaction testing of cerebrospinal fluid. Among the 175 LE, median peak weekly incidence rate in LE due to NmA, W, X and C were 54, 39, 109 and 46 per 100,000, respectively. These differences impacted ability of the epidemic to be detected at the district level. While this analysis is limited by the small number of LE due to NmX (N = 4) and NmW (N = 5), further research should explore whether strategies for prevention and response to meningitis epidemics need to be adapted according to predominant meningococcal serogroups. PMID- 27657531 TI - Co-occurrence of Pain Symptoms and Somatosensory Sensitivity in Burning Mouth Syndrome: A Systematic Review. AB - BACKGROUND: Burning mouth syndrome (BMS) is a chronic and spontaneous oral pain with burning quality in the tongue or other oral mucosa without any identifiable oral lesion or laboratory finding. Pathogenesis and etiology of BMS are still unknown. However, BMS has been associated with other chronic pain syndromes including other idiopathic orofacial pain, the dynias group and the family of central sensitivity syndromes. This would imply that BMS shares common mechanisms with other cephalic and/or extracephalic chronic pains. The primary aim of this systematic review was to determine whether BMS is actually associated with other pain syndromes, and to analyze cephalic and extracephalic somatosensory sensitivity in these patients. METHODS: This report followed the PRISMA Statement. An electronic search was performed until January 2015 in PubMed, Cochrane library, Wiley and ScienceDirect. Searched terms included "burning mouth syndrome OR stomatodynia OR glossodynia OR burning tongue OR oral burning". Studies were selected according to predefined inclusion criteria (report of an association between BMS and other pain(s) symptoms or of cutaneous cephalic and/or extracephalic quantitative sensory testing in BMS patients), and a descriptive analysis conducted. RESULTS: The search retrieved 1512 reports. Out of these, twelve articles met criteria for co-occurring pain symptoms and nine studies for quantitative sensory testing (QST) in BMS patients. The analysis reveals that in BMS patients co-occurring pain symptoms are rare, assessed by only 0.8% (12 of 1512) of the retrieved studies. BMS was associated with headaches, TMD, atypical facial pain, trigeminal neuralgia, post-herpetic facial pain, back pain, fibromyalgia, joint pain, abdominal pain, rectal pain or vulvodynia. However, the prevalence of pain symptoms in BMS patients is not different from that in the age-matched general population. QST studies reveal no or inconsistent evidence of abnormal cutaneous cephalic and extracephalic somatosensory sensitivity. CONCLUSIONS: There is no evidence for a high rate of other pain symptoms or somatosensory impairments co-occurring with BMS. These results thus suggest that BMS rather depends on specific mechanisms, likely at the trigeminal level. Nevertheless, more thoroughly conducted research is required to draw definitive conclusion. PMID- 27657532 TI - Disease Phenotypes in a Mouse Model of RNA Toxicity Are Independent of Protein Kinase Calpha and Protein Kinase Cbeta. AB - Myotonic dystrophy type 1(DM1) is the prototype for diseases caused by RNA toxicity. RNAs from the mutant allele contain an expanded (CUG)n tract within the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The toxic RNAs affect the function of RNA binding proteins leading to sequestration of muscleblind-like (MBNL) proteins and increased levels of CELF1 (CUGBP, Elav-like family member 1). The mechanism for increased CELF1 is not very clear. One favored proposition is hyper-phosphorylation of CELF1 by Protein Kinase C alpha (PKCalpha) leading to increased CELF1 stability. However, most of the evidence supporting a role for PKC-alpha relies on pharmacological inhibition of PKC. To further investigate the role of PKCs in the pathogenesis of RNA toxicity, we generated transgenic mice with RNA toxicity that lacked both the PKCalpha and PKCbeta isoforms. We find that these mice show similar disease progression as mice wildtype for the PKC isoforms. Additionally, the expression of CELF1 is also not affected by deficiency of PKCalpha and PKCbeta in these RNA toxicity mice. These data suggest that disease phenotypes of these RNA toxicity mice are independent of PKCalpha and PKCbeta. PMID- 27657533 TI - Crystal Structure of the Escherichia coli Fic Toxin-Like Protein in Complex with Its Cognate Antitoxin. AB - FIC domain proteins mediate post-translational modifications of target proteins, which typically results in their inactivation. Depending on the conservation of crucial active site residues, the FIC fold serves as structural scaffold for various enzymatic activities, mostly target adenylylation. The founding member of the vast Fic protein family, EcFicT, was identified in Escherichia coli some time ago. The G55R point mutant of EcFicT displays the "filamentation induced by cAMP" (Fic) phenotype at high 3',5'-cyclic adenosine monophosphate (cAMP) concentrations and elevated temperature, but the underlying molecular mechanism and any putative biochemical activity of EcFicT have remained unknown. EcFicT belongs to class I Fic toxin proteins that are encoded together with a small inhibitory protein (antitoxin), named EcFicA in E. coli. Here, we report the crystal structures of two mutant EcFicT/EcFicA complexes (EcFicTG55RA and EcFicTAE28G) both showing close resemblance with the structure of the AMP transferase VbhT from Bartonella schoenbuchensis in complex with its cognate antitoxin VbhA. However, crucial differences in the active site of EcFicT compared to VbhT and other AMP-transferases rationalize the lack of evidence for adenylylation activity. Comprehensive bioinformatic analysis suggests that EcFicT has evolved from canonical AMP-transferases and has acquired a conserved binding site for a yet to be discovered novel substrate. The G55R mutation has no effect on structure or thermal stability of EcFicT, such that the molecular basis for its associated Fic phenotype remains elusive. We anticipate that this structure will inspire further bioinformatic and experimental analyses in order to characterize the enzymatic activity of EcFicT and help revealing its physiological role. PMID- 27657536 TI - Development of the PHASE-Proxy scale for rating drug-related signs and symptoms in severe cognitive impairment. AB - OBJECTIVES: The need for assessment of possible drug-related signs and symptoms in older people with severe cognitive impairment has increased. In 2009, the PHASE-20 rating scale for identifying symptoms possibly related to medication was the first such scale to be found valid and reliable for use with elderly people. In this project, the aim was to develop and examine the psychometric properties and clinical utility of PHASE-Proxy, a similar scale for proxy use in assessing elderly people with cognitive impairment. METHODS: Three expert groups revised PHASE-20 into a preliminary proxy version, which was then tested for inter-rater reliability, internal consistency, and content validity. Its clinical usefulness was investigated by pharmacist-led medication reviews. Group interviews and a study-specific questionnaire with nursing home staff were used to investigate the feasibility of use. RESULTS: The PHASE-Proxy scale had satisfactory levels of inter-rater reliability (Spearman's rank correlation coefficient; rs = 0.8), and acceptable internal consistency (Cronbach's alpha coefficient; alpha = 0.73). The factor analysis resulted in a logical solution with seven factors, grouped into two dimensions: signs of emotional distress and signs of physical discomfort. The medication reviews, interviews, and questionnaires also found the proxy scale to be clinically useful, and feasible to use. CONCLUSION: The PHASE-Proxy scale appears to be a valid instrument that enables proxies to reliably assess nursing home residents who cannot participate in the assessment, to identify possible drug-related signs and symptoms. It also appears to be clinically useful and feasible for use in this population. PMID- 27657535 TI - Normal Development and Function of T Cells in Proline Rich 7 (Prr7) Deficient Mice. AB - Transmembrane adaptor proteins (TRAPs) are important organisers for the transduction of immunoreceptor-mediated signals. Prr7 is a TRAP that regulates T cell receptor (TCR) signalling and potently induces cell death when overexpressed in human Jurkat T cells. Whether endogenous Prr7 has a similar functional role is currently unknown. To address this issue, we analysed the development and function of the immune system in Prr7 knockout mice. We found that loss of Prr7 partially impairs development of single positive CD4+ T cells in the thymus but has no effect on the development of other T cell subpopulations, B cells, NK cells, or NKT cells. Moreover, Prr7 does not affect the TCR signalling pathway as T cells derived from Prr7 knockout and wild-type animals and stimulated in vitro express the same levels of the activation marker CD69, and retain their ability to proliferate and activate induced cell death programs. Importantly, Prr7 knockout mice retained the capacity to mount a protective immune response when challenged with Listeria monocytogenes infection in vivo. In addition, T cell effector functions (activation, migration, and reactivation) were normal following induction of experimental autoimmune encephalomyelitis (EAE) in Prr7 knockout mice. Collectively, our work shows that loss of Prr7 does not result in a major immune system phenotype and suggests that Prr7 has a dispensable function for TCR signalling. PMID- 27657534 TI - Recombinant Atrial Natriuretic Peptide Prevents Aberrant Ca2+ Leakage through the Ryanodine Receptor by Suppressing Mitochondrial Reactive Oxygen Species Production Induced by Isoproterenol in Failing Cardiomyocytes. AB - Catecholamines induce intracellular reactive oxygen species (ROS), thus enhancing diastolic Ca2+ leakage through the ryanodine receptor during heart failure (HF). However, little is known regarding the effect of atrial natriuretic peptide (ANP) on ROS generation and Ca2+ handling in failing cardiomyocytes. The aim of the present study was to clarify the mechanism by which an exogenous ANP exerts cardioprotective effects during HF. Cardiomyocytes were isolated from the left ventricles of a canine tachycardia-induced HF model and sham-operated vehicle controls. The degree of mitochondrial oxidized DNA was evaluated by double immunohistochemical (IHC) staining using an anti-VDAC antibody for the mitochondria and an anti-8-hydroxy-2'-deoxyguanosine antibody for oxidized DNA. The effect of ANP on ROS was investigated using 2,7-dichlorofluorescin diacetate, diastolic Ca2+ sparks assessed by confocal microscopy using Fluo 4-AM, and the survival rate of myocytes after 48 h. The double IHC study revealed that isoproterenol (ISO) markedly increased oxidized DNA in the mitochondria in HF and that the ISO-induced DNA damage was markedly inhibited by the co-presence of ANP. ROS production and Ca2+ spark frequency (CaSF) were increased in HF compared to normal controls, and were further increased in the presence of ISO. Notably, ANP significantly suppressed both ISO-induced ROS and CaSF without changing sarcoplasmic reticulum Ca2+ content in HF (p<0.01, respectively). The survival rate after 48 h in HF was significantly decreased in the presence of ISO compared with baseline (p<0.01), whereas it was significantly improved by the co-presence of ANP (p<0.01). Together, our results suggest that ANP strongly suppresses ISO induced mitochondrial ROS generation, which might correct aberrant diastolic Ca2+ sparks, eventually contributing to the improvement of cardiomyocyte survival in HF. PMID- 27657538 TI - Correction: Evaluating the Operational Features of an Unconventional Dual-Bay U Turn Design for Intersections. AB - [This corrects the article DOI: 10.1371/journal.pone.0158914.]. PMID- 27657537 TI - The Influence of a Sudden Increase in Playing Time on Playing-Related Musculoskeletal Complaints in High-Level Amateur Musicians in a Longitudinal Cohort Study. AB - BACKGROUND: Several studies in the domain of professional musicians describe the relation between playing time and the occurrence of musculoskeletal complaints in professional musicians. To date, no longitudinal cohort study into this relationship has been performed and no amateur musicians were studied. Therefore, the aim of this study is to examine the causal relationship between a sudden increase in playing time among amateur musicians on the occurrence of musculoskeletal complaints in a prospective cohort study. METHODS: All members of two national Dutch Students Orchestras were asked to participate in the study. These project-based orchestras, consisting of high-level amateurs, followed a nine-hour rehearsing schedule for ten consecutive days. On the first day (t0) and after one week (t1) the subjects were asked to complete a paper-based questionnaire including sociodemographic characteristics, music-related questions, questions regarding playing-related musculoskeletal complaints and the music module of the disabilities of arm, shoulder and hand questionnaire. RESULTS: The NSO consisted of 85 and the NESKO of 41 members during the study period. 59 subjects completed the questionnaire at both timepoints (response rate 47%). 9 subjects were excluded for being a music academy student, leaving 50 subjects (mean age 22.1, 72% female) suitable for analysis. During the rehearsal week, the prevalence of at least one playing-related musculoskeletal complaint increased from 28% to 80%. The most frequently affected areas were the neck, upper and lower back, hand/and or wrists and shoulders. The DASH music module score increased from 14 at t0 to 23 at t1. CONCLUSION: A point prevalence of 28% at the start of the study that increased remarkably to 80% within a one-week period. Future research should evaluate other risk factors for musculoskeletal complaints in amateur musicians. These risk factors should be the base for the development of preventive measures. PMID- 27657539 TI - Dielectric properties of dog brain tissue measured in vitro across the 0.3-3 GHz band. AB - Dielectric properties of dead Greyhound female dogs' brain tissues at different ages were measured at room temperature across the frequency range of 0.3-3 GHz. Measurements were made on excised tissues, in vitro in the laboratory, to carry out dielectric tests on sample tissues. Each dataset for a brain tissue was parametrized using the Cole-Cole expression, and the relevant Cole-Cole parameters for four tissue types are provided. A comparison was made with the database available in literature for other animals and human brain tissue. Results of two types of tissues (white matter and skull) showed systematic variation in dielectric properties as a function of animal age, whereas no significant change related to age was noticed for other tissues. Results provide critical information regarding dielectric properties of animal tissues for a realistic animal head model that can be used to verify the validity and reliability of a microwave head scanner for animals prior to testing on live animals. Bioelectromagnetics. 37:549-556, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27657540 TI - Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study. AB - BACKGROUND: This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients. METHODS: A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147) were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association. RESULTS: We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27-10.64, p<0.05) and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40-6.24, p<0.001) were associated with a dose dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20-3.44, p<0.01), there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis. CONCLUSIONS: Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy. PMID- 27657542 TI - The Natural History of Epilepsy in 163 Untreated Patients: Looking for "Oligoepilepsy". AB - : The clinical evolution of untreated epilepsy has been rarely studied in developed countries, and the existence of a distinct syndrome characterized by rarely repeated seizures (oligoepilepsy) is debated. The aim of this study is to assess the natural history of 163 untreated patients with epilepsy in order to evaluate whether oligoepilepsy retains specific features. We retrospectively evaluated 7344 patients with >=2 unprovoked seizures. INCLUSION CRITERIA: sufficient anamnestic/EEG data, disease duration >=10 years, follow-up >=3 years. EXCLUSION CRITERIA: psychogenic seizures, natural history of disease <5 years. The 163 included subjects were divided into 2 groups according to seizure frequency: oligoepilepsy (<=1/year; 47 subjects) and controls (>1/year; 116 subjects). We also evaluated seizure frequency during the natural history. There were no differences between groups regarding duration of natural history, family history of epilepsy/febrile seizures, interictal EEG. Subjects with oligoepilepsy differed from controls in terms of sex (females 38% vs. 58%, p = 0.03) and drug resistance (6% vs 28%; p = 0.003). Juvenile myoclonic epilepsy was more frequent in controls (9.5% vs 0%, p = 0.04). Patients with oligoepilepsy, differently from controls, had stable seizure frequency. Oligoepilepsy represents a favourable evolution of different epileptic syndromes and keeps a stable seizure frequency over time. PMID- 27657541 TI - Optogenetic activation of melanin-concentrating hormone neurons increases non rapid eye movement and rapid eye movement sleep during the night in rats. AB - Neurons containing melanin-concentrating hormone (MCH) are located in the hypothalamus. In mice, optogenetic activation of the MCH neurons induces both non rapid eye movement (NREM) and rapid eye movement (REM) sleep at night, the normal wake-active period for nocturnal rodents [R. R. Konadhode et al. (2013) J. Neurosci., 33, 10257-10263]. Here we selectively activate these neurons in rats to test the validity of the sleep network hypothesis in another species. Channelrhodopsin-2 (ChR2) driven by the MCH promoter was selectively expressed by MCH neurons after injection of rAAV-MCHp-ChR2-EYFP into the hypothalamus of Long Evans rats. An in vitro study confirmed that the optogenetic activation of MCH neurons faithfully triggered action potentials. In the second study, in Long Evans rats, rAAV-MCH-ChR2, or the control vector, rAAV-MCH-EYFP, were delivered into the hypothalamus. Three weeks later, baseline sleep was recorded for 48 h without optogenetic stimulation (0 Hz). Subsequently, at the start of the lights off cycle, the MCH neurons were stimulated at 5, 10, or 30 Hz (1 mW at tip; 1 min on - 4 min off) for 24 h. Sleep was recorded during the 24-h stimulation period. Optogenetic activation of MCH neurons increased both REM and NREM sleep at night, whereas during the day cycle, only REM sleep was increased. Delta power, an indicator of sleep intensity, was also increased. In control rats without ChR2, optogenetic stimulation did not increase sleep or delta power. These results lend further support to the view that sleep-active MCH neurons contribute to drive sleep in mammals. PMID- 27657543 TI - Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia. AB - BACKGROUND: Predicting outcomes for patients with acute myeloid leukemia (AML) on the basis of pretreatment predictors has been the cornerstone of management. Posttreatment prognostic factors are increasingly being evaluated. METHODS: Among 280 younger patients who were treated with intermediate-dose cytarabine (total >= 5 g/m2 ) and idarubicin-based induction chemotherapy and achieved remission, 186 were assessed for minimal residual disease (MRD) with an 8-color multiparameter flow cytometry panel performed on bone marrow specimens with a sensitivity of 0.1% or higher. RESULTS: One hundred sixty-six patients had samples available 1 to 2 months after induction at the time of complete remission (CR), and 79% became negative for MRD, with an MRD-negative status associated with an improvement in relapse-free survival (RFS; P = .0002) and overall survival (OS; P = .0002). One hundred sixteen were evaluated for their MRD status during consolidation, and 86% were negative, with an MRD-negative status associated with a significant improvement in RFS (P < .0001) and OS (P < .0001). Sixty-nine patients were evaluated for their MRD status after completion of all therapy, and 84% were negative, with an MRD-negative status associated with an improvement in RFS (P < .0001) and OS (P < .0001). In a multivariate analysis including age, cytogenetics, response (CR vs CR with incomplete platelet recovery/incomplete blood count recovery), and MRD, achieving an MRD-negative status was the most important independent predictor of RFS and OS at response (P = .008 and P = .0008, respectively), during consolidation (P < .0001 for both), and at the completion of therapy (P < .0001 and P = .002, respectively). CONCLUSIONS: Achieving an MRD-negative status according to multiparameter flow cytometry is associated with a highly significant improvement in the outcomes of younger patients with AML receiving cytosine arabinoside plus idarubicin-based induction and consolidation regimens. Cancer 2017;123:426-435. (c) 2016 American Cancer Society. PMID- 27657544 TI - Reduced Risk of Importing Ebola Virus Disease because of Travel Restrictions in 2014: A Retrospective Epidemiological Modeling Study. AB - BACKGROUND: An epidemic of Ebola virus disease (EVD) from 2013-16 posed a serious risk of global spread during its early growth phase. A post-epidemic evaluation of the effectiveness of travel restrictions has yet to be conducted. The present study aimed to estimate the effectiveness of travel restrictions in reducing the risk of importation from mid-August to September, 2014, using a simple hazard based statistical model. METHODOLOGY/PRINCIPAL FINDINGS: The hazard rate was modeled as an inverse function of the effective distance, an excellent predictor of disease spread, which was calculated from the airline transportation network. By analyzing datasets of the date of EVD case importation from the 15th of July to the 15th of September 2014, and assuming that the network structure changed from the 8th of August 2014 because of travel restrictions, parameters that characterized the hazard rate were estimated. The absolute risk reduction and relative risk reductions due to travel restrictions were estimated to be less than 1% and about 20%, respectively, for all models tested. Effectiveness estimates among African countries were greater than those for other countries outside Africa. CONCLUSIONS: The travel restrictions were not effective enough to expect the prevention of global spread of Ebola virus disease. It is more efficient to control the spread of disease locally during an early phase of an epidemic than to attempt to control the epidemic at international borders. Capacity building for local containment and coordinated and expedited international cooperation are essential to reduce the risk of global transmission. PMID- 27657545 TI - Separating Timing, Movement Conditions and Individual Differences in the Analysis of Human Movement. AB - A central task in the analysis of human movement behavior is to determine systematic patterns and differences across experimental conditions, participants and repetitions. This is possible because human movement is highly regular, being constrained by invariance principles. Movement timing and movement path, in particular, are linked through scaling laws. Separating variations of movement timing from the spatial variations of movements is a well-known challenge that is addressed in current approaches only through forms of preprocessing that bias analysis. Here we propose a novel nonlinear mixed-effects model for analyzing temporally continuous signals that contain systematic effects in both timing and path. Identifiability issues of path relative to timing are overcome by using maximum likelihood estimation in which the most likely separation of space and time is chosen given the variation found in data. The model is applied to analyze experimental data of human arm movements in which participants move a hand-held object to a target location while avoiding an obstacle. The model is used to classify movement data according to participant. Comparison to alternative approaches establishes nonlinear mixed-effects models as viable alternatives to conventional analysis frameworks. The model is then combined with a novel factor analysis model that estimates the low-dimensional subspace within which movements vary when the task demands vary. Our framework enables us to visualize different dimensions of movement variation and to test hypotheses about the effect of obstacle placement and height on the movement path. We demonstrate that the approach can be used to uncover new properties of human movement. PMID- 27657546 TI - Preoperative Pulmonary Nodule Localization: A Comparison of Methylene Blue and Hookwire Techniques. AB - OBJECTIVE: Small pulmonary nodules are often difficult to identify during thoracoscopic resection, and preoperative CT-guided localization performed using either hookwire placement or methylene blue injection can be helpful. The purpose of this study is to compare the localization success and complication rates of these two techniques. MATERIALS AND METHODS: One hundred two consecutive patients who underwent a total of 109 localization procedures performed with CT fluoroscopic guidance were analyzed. The procedures included 52 hookwire insertions and 57 methylene blue injections. The localization success and complication rates associated with the two groups were compared. RESULTS: All nodules in both groups were identified intraoperatively, except for those in two patients in the hookwire group who did not proceed to undergo same-day surgery, including one with a massive systemic air embolus that resulted in death. Hookwires were dislodged in seven of 52 cases (13%), but the surgeons were still able to locate the nodules through visualization of the parenchymal puncture sites. The total number of complications was higher in the hookwire insertion group than in the methylene blue injection group, but this trend was not statistically significant, with all types of complications occurring in 28 cases (54%) versus 26 cases (46%) (p = 0.45), major complications noted in four cases (8%) versus one case (2%) (p = 0.19), pneumothorax observed in 20 cases (38%) versus 14 cases (25%) (p = 0.15), and perilesional hemorrhage occurring in six cases (12%) versus two cases (4%) (p = 0.15), respectively. CONCLUSION: The present study suggests that methylene blue injection and hookwire insertion are statistically equivalent for preoperative pulmonary nodule localization; however, seven of 52 hookwires dislodged, and trends toward more frequent and severe complications were noted in the hookwire insertion group. PMID- 27657547 TI - OMIPs start school. PMID- 27657548 TI - Clinical Utility of the Difficulty Scoring System for Predicting Surgical Time of Laparoscopic Liver Resection. PMID- 27657549 TI - Ketosis-prone atypical diabetes in Cameroonian people with hyperglycaemic crisis: frequency, clinical and metabolic phenotypes. AB - AIM: It is unclear whether ketosis-prone diabetes is a specific type or a subtype of Type 2 diabetes. We aimed to describe the clinical and metabolic features of ketosis-prone diabetes in a sub-Saharan population. METHODS: We consecutively enrolled and characterized 173 people with non-autoimmune diabetes admitted for hyperglycaemic crisis at the Yaounde Central Hospital, Cameroon. Blood samples were collected for fasting glucose, HbA1c , lipid profile and C-peptide assays with insulin resistance and secretion estimation by homeostasis model assessment. People were classified as having Type 2 diabetes (n = 124) or ketosis-prone diabetes (n = 49). Ketosis-prone diabetes was sub-classified as new-onset ketotic phase (n = 34) or non-ketotic phase (n = 15). RESULTS: Ketosis-prone diabetes was found in 28.3% of the hyperglycaemic crises. Age at diabetes diagnosis was comparable in Type 2 and ketosis-prone diabetes [48 +/- 14 vs 47 +/- 11 years; P = 0.13] with a similar sex distribution. Overall BMI was 27.7 +/- 13.4 kg/m2 and was >= 25 kg/m2 in 55.8% of those taking part, however, 73.5% of those with ketosis-prone diabetes reported weight loss of > 5% at diagnosis. Blood pressure and lipid profile were comparable in both types. Ketosis-prone diabetes in the ketotic phase was characterized by lower insulin secretion and higher serum triglycerides compared with non-ketotic ketosis prone and Type 2 diabetes. Type 2 and ketosis prone diabetes in the non-ketotic phase were comparable in terms of lipid profile, blood pressure, waist-to-hip ratio, BMI and fat mass, insulin secretion and insulin resistance indices. CONCLUSIONS: Ketosis-prone diabetes is likely to be a subtype of Type 2 diabetes with the potential to develop acute insulinopenic episodes. PMID- 27657551 TI - The salt-regulated element in the promoter of lycopene beta-cyclase gene confers a salt regulatory pattern in carotenogenesis of Dunaliella bardawil. AB - In the carotenoid biosynthesis, lycopene beta-cyclase (LCYb) is a key regulatory enzyme involved in the conversion of lycopene into beta-carotene. Under stress conditions, such as high salinity, high light and nutrient deprivation, large amounts of beta-carotene can be accumulated in Dunaliella bardawil. To study on the molecular responses of salt stress in D. bardawil is of great significance to reveal the mechanisms of salt tolerance and engineer crop plants to be salt tolerant. In this study, the full-length coding sequence of lcyb from D. bardawil (Dblcyb, GenBank: KX218392) was isolated by transcriptome sequencing. Then, the genomic sequence, promoter and terminator regions of Dblcyb were isolated by genome walking. The Dblcyb promoter (GenBank: KX218393) contained several typical transcription boxes, multiple light response elements and a salt-regulated element (SRE, GT1GMSCAM4). Dbpsy and Dblcyb responsible for beta-carotene biosynthesis in D. bardawil was shown to be up-regulated under salt stress and their promoters contained the common SRE. By element deletion analysis and using Ble-EGFP as the reporter, the salt-inducible SRE was confirmed to confer salt induced expression of Dblcyb promoter. It was indicated that the salt-regulated expression of Dblcyb may be attributed to the salt-responsive element (GT1GMSCAM4) and the GT-rich region in its genomic sequence. PMID- 27657550 TI - Removal of dentin non-collagenous structures results in the unraveling of microfibril bundles in collagen type I. AB - AIMS: The structural organization of collagen from mineralized tissues, such as dentin and bone, has been a topic of debate in the recent literature. Recent reports have presented novel interpretations of the complexity of collagen type I at different hierarchical levels and in different tissues. Here, we investigate the nanostructural organization of demineralized dentin collagen following the digestion of non-collagenous components with a trypsin enzyme. MATERIALS AND METHODS: Dentin specimens were obtained from healthy third-molars, cut into small cubes, and polished down to 1 um roughness. Samples were then demineralized with 10% citric acid for 2 min. Selected specimens were further treated with a solution containing 1 mg/ml trypsin for 48 hours at 37 degrees C (pH 7.9-9.0). Both untreated and trypsin digested samples were analyzed using SDS-PAGE, Field Emission Scanning Electron Microscopy (FE-SEM), and nanoindentation, where surface hardness and creep properties were compared before and after treatments. RESULTS: FE-SEM images of demineralized dentin showed the banded morphology of D periodical collagen type I, which upon enzymatic digestion with trypsin appeared to dissociate longitudinally, consistently unraveling ~20 nm structures (microfibril bundles). Such nanoscale structures, to the best of our knowledge, have not been characterized in dentin previously. Mechanical characterization via nanoindentation showed that the unraveling of such microfibril bundles affected the creep displacement and creep rate of demineralized dentin. CONCLUSION: In summary, our results provide novel evidence of the organization of collagen type I from dentin, which may have important implications for the interaction of dental materials with the organic dentin matrix and the mechanical properties of mineralized tissues. PMID- 27657552 TI - Sarcoidosis in the Head and Neck: An Illustrative Review of Clinical Presentations and Imaging Findings. AB - OBJECTIVE: Sarcoidosis is referred to as a great imitator because of its propensity to radiologically mimic a variety of pathologic entities. Symptomatic neurosarcoidosis is present in approximately 5% of patients with sarcoidosis, and it is found histopathologically in approximately 25% of asymptomatic patients. CONCLUSION: An understanding of the multifaceted imaging manifestations of head and neck sarcoidosis will aid early recognition of the diagnosis, with a goal for earlier initiation of therapy and prevention of irreversible sequelae of the disease. PMID- 27657553 TI - The Cross-Link between Adipokines, Insulin Resistance and Obesity in Offspring of Diabetic Pregnancies. AB - BACKGROUND/AIMS: Intrauterine exposure to hyperglycemia might impact the risk for future metabolic deteriorations. The aim was to characterize the association between different adipokines and neuropeptides and insulin resistance and BMI-SDS in children affected by diabetes during pregnancy. METHODS: 76 children (mean age: 6 years, male:female = 36:40) born to mothers with gestational or pregestational diabetes and nondiabetic women were consecutively included for clinical assessments comprising anthropometrics and metabolic characterization [2 hour glucose tolerance test, leptin, peptide YY (PYY), neuropeptide Y (NPY), ghrelin, growth differentiation factor 15 (GDF-15), and adiponectin]. RESULTS: The level of insulin resistance was associated with BMI-SDS (p < 0.001), leptin (p < 0.001), ghrelin (p = 0.002), age (p < 0.002) and negatively with GDF-15 (p = 0.005). BMI-SDS, leptin and GDF-15 were shown to have independent effects on insulin resistance by using a multiple regression model (additionally including age, and maternal diabetes status), whereas ghrelin lost significance (p = 0.345). No differences were present in adipokines and insulin resistance when children were evaluated by maternal glucometabolic status. However, we observed more strengthened associations between insulin resistance and covariates BMI-SDS and leptin in offspring of diabetic pregnancies. CONCLUSIONS: Young children with elevated BMI or leptin are affected by higher indices of insulin resistance, particularly those who were born to mothers with diabetes during pregnancy. The impact of this special risk constellation should be considered in future studies. PMID- 27657554 TI - Prescription of asthma medications before and during pregnancy in France: An observational drug study using the EFEMERIS database. AB - OBJECTIVE: Asthma affects between 3% to 8% of pregnant women. Previous studies have suggested that women's prescriptions for asthma medications change during pregnancy. The aim was to describe the prescription of asthma medications before and during pregnancy in France. METHODS: Women from the EFEMERIS, a French database assessing the drugs prescribed, dispensed and reimbursed during pregnancy, delivering between July 2004 and December 2012, were included. Women, who were dispensed asthma medications on at least two dates from 3 months prior to pregnancy through delivery, were considered. RESULTS: 2,977 women out of 69,205 (4%) were selected. They were prescribed 2.4 +/- 1.2 different anti asthmatic drugs with 3.5 +/- 2.7 different dispensing dates. Almost 62% of the women were dispensed at least one prescription for short-acting beta2-agonist (SABA), 63% at least one inhaled corticosteroid (IC), 42% a fixed-combination of an IC and a long-acting beta2-agonist (LABA) and 8% a LABA. An increase in SABA and IC prescriptions and a decrease in fixed-combination prescriptions were observed during pregnancy compared to pre-pregnancy period. A rapid drop in prescriptions for montelukast was observed. Among the 1,507 women who were prescribed asthma medication before pregnancy, one third had a drop in dispensed asthma medications from the beginning of pregnancy. CONCLUSIONS: The prevalence of dispensed asthma medications varies during pregnancy. There is a decrease in the prescriptions of fixed-combinations during pregnancy and an increase in the prescriptions of ICs. It appears important to study the potential impact of such changes on fetuses and newborns. PMID- 27657555 TI - Medical Neighborhood Model for the Care of Chronic Kidney Disease Patients. AB - BACKGROUND: The patient-centered medical home is a popular model of care, but the patient-centered medical neighborhood (PCMN) is rarely described. We developed a PCMN in an academic practice to improve care for patients with chronic kidney disease (CKD). The purpose of this study is to identify the prevalence of CKD in this practice and describe baseline characteristics, develop an interdisciplinary team-based approach to care and determine cost associated with CKD patients. METHODS: Patients with CKD stage 3a with comorbidities through stage 5 were identified. Data collected include demographics, comorbidities and whether patients had a nephrologist. Using a screening tool based on the 2012 Kidney Disease Improving Global Outcomes guidelines, a nurse care manager (NCM) made recommendations about management including indications for referral. A pharmacist reviewed patients' charts and made medication-related recommendations. Blue Cross Blue Shield (BCBS) insurance provided cost data for a subset of patients. RESULTS: A total of 1,255 patients were identified. Half did not have a formal diagnosis of CKD and three-quarters had never seen a nephrologist. Based on the results of the screening tool, the NCM recommended nephrology E-consult or full consult for 85 patients. The subset of BCBS patients had a mean healthcare cost of $1,528.69 per member per month. CONCLUSIONS: We implemented a PCMN that allowed for easy identification of a high-risk, high-cost population of CKD patients and optimized their care to reflect guideline-based standards. PMID- 27657556 TI - Olive oil authentication: A comparative analysis of regulatory frameworks with especial emphasis on quality and authenticity indices, and recent analytical techniques developed for their assessment. A review. AB - Over the last decades, olive oil quality and authenticity control has become an issue of great importance to consumers, suppliers, retailers, and regulators in both traditional and emerging olive oil producing countries, mainly due to the increasing worldwide popularity and the trade globalization of this product. Thus, in order to ensure olive oil authentication, various national and international laws and regulations have been adopted, although some of them are actually causing an enormous debate about the risk that they can represent for the harmonization of international olive oil trade standards. Within this context, this review was designed to provide a critical overview and comparative analysis of selected regulatory frameworks for olive oil authentication, with special emphasis on the quality and purity criteria considered by these regulation systems, their thresholds and the analytical methods employed for monitoring them. To complete the general overview, recent analytical advances to overcome drawbacks and limitations of the official methods to evaluate olive oil quality and to determine possible adulterations were reviewed. Furthermore, the latest trends on analytical approaches to assess the olive oil geographical and varietal origin traceability were also examined. PMID- 27657557 TI - Dynein: Let's not get stuck! PMID- 27657559 TI - Colonic Adenocarcinoma Presenting as Sigmoidorectal Intussusception: A Consideration for Intussusception Reduction. PMID- 27657558 TI - A Rare Case of Plasmablastic Lymphoma Mimicking Adenocarcinoma of the Sigmoid Colon. PMID- 27657560 TI - A Trauma Patient Advocate Is a Valuable Addition to the Multidisciplinary Trauma Team: A Process Improvement Project. PMID- 27657561 TI - Gastric Adenocarcinoma Presenting after Revisional Roux-en-Y Gastric Bypass. PMID- 27657562 TI - Variation in Follow-up of Asymptomatic Breast Cancer Patients: Can We Choose More Wisely? PMID- 27657563 TI - Pediatric Falls in a Nonpediatric Trauma Center-When Is Trauma Team Activation Needed? PMID- 27657564 TI - Overwhelming Recurrent Clostridium difficile Infection after Reversal of Diverting Loop Ileostomy Created for Prior Fulminant C. difficile Colitis. PMID- 27657565 TI - Spontaneous Renal Calyceal Rupture: A Rare Cause of an Acute Abdomen in Pregnancy. PMID- 27657566 TI - Modern Management of Medieval Injury: Cardiac Trauma Sustained by Crossbow. PMID- 27657567 TI - Management of Mangled Extremity from Shotgun Blast Injury. PMID- 27657568 TI - Two Separate Colorectal Granular Cell Tumors. PMID- 27657569 TI - Splenectomy for Primary and Secondary Splenic Neoplasm. PMID- 27657571 TI - Appendix Neoplasms in a Rural County: A Review of an Unexpected Number of Cases. PMID- 27657570 TI - Malignant Large Bowel Obstruction: A Rare Presentation of Metastatic Pancreatic Cancer. PMID- 27657572 TI - Nonoperative Management of a Penetrating Injury to the Retrohepatic Inferior Vena Cava. PMID- 27657573 TI - Symptomatic Late Saphenous Vein Graft Aneurysm in an Upper Extremity Bypass. PMID- 27657574 TI - Ileal Volvulus with Chronic Obstruction. PMID- 27657575 TI - Novel Treatment of Acute Respiratory Distress Syndrome after Chlorine Gas Inhalation Injury. PMID- 27657576 TI - Recanalized Umbilical Vein as a Source of Hemorrhagic Shock. PMID- 27657577 TI - Delayed Splenic Rupture with Normal Admission CT Scan after Blunt Trauma. PMID- 27657578 TI - Survival of Left Chest and Mediastinal Impalement with a Fence Post. PMID- 27657579 TI - Quantification of the Effect of Diabetes Mellitus on Ventral Hernia Repair: Results from Two National Registries. AB - Two national databases were analyzed to determine the effect of varying severity of diabetes mellitus (DM) on ventral hernia repair (VHR) outcomes. The National Surgical Quality Improvement Program (NSQIP) and the National Inpatient Sample (NIS) were queried for patients with and without DM who underwent elective VHR between 2005 to 2012 and 1998 to 2011, respectively. In addition, patients with insulin dependent versus noninsulin-dependent DM were compared in NSQIP; complicated and uncomplicated diabetics were compared in NIS. Univariate and multivariate analyses were used. In NSQIP, 25,819 of 219,625 patients undergoing VHR were diabetic. In open VHR (OVHR), DM patients had an increased complication rate (P < 0.0001); DM patients requiring insulin had increased odds of wound, minor, and major complications (P < 0.0001). For laparoscopic VHR (LVHR), insulin dependence did not affect complication rates (P > 0.05). In NIS, 45,248 of 238,627 patients undergoing VHR were diabetic. In OVHR, patients with complicated diabetes had higher rates of minor complications (17.3% vs 12.7%, P < 0.0001) and had 58 per cent greater odds of major complications than patients with uncomplicated diabetes. LVHR had no difference in complications for complicated versus uncomplicated DM (P > 0.05). After multivariate analysis, insulin dependent or complicated DM undergoing OVHR had significantly worse outcomes compared with noninsulin-dependent and uncomplicated diabetics. Preoperative optimization and LVHR should be considered in diabetic patients. PMID- 27657580 TI - Unnecessary Transfers for Acute Surgical Care: Who and Why? AB - Interhospital transfers for acute surgical care occur commonly, but without clear guidelines or protocols. Transfers may subject patients and delivery systems to significant burdens without clear clinical benefit. The incidence and factors associated with unnecessary transfers are not well described. We conducted a retrospective cohort study of patient transfers within a regional referral network to a tertiary center for nontrauma acute surgical care from 2009 to 2013. Clinically unnecessary transfers were defined as transfers that resulted in no intervention (operation, endoscopy, or interventional radiology procedure) and discharge to home within 72 hours. We performed bivariate and multivariate logistic regression analyses. The study population included 2177 patient transfers, 19 per cent of which were determined to be clinically unnecessary. After adjustment, clinically unnecessary transfers were more commonly performed for patient request (odds ratio = 2.52, 95% confidence interval = 1.60-3.99), continuity of care (1.87, 1.44-2.42), and care by urologic (1.50, 1.06-2.13) and vascular services (1.44, 1.03-2.01). Patients with higher comorbidity and severity of illness scores were less likely to have unnecessary transfers. The burden of unnecessary transfers could be mitigated by identifying appropriate transfer candidates through mutually developed guidelines, interfacility collaboration, and increased use of remote care to provide surgical subspecialty consultation and maintain continuity. PMID- 27657581 TI - Alternatives to Indwelling Catheters Cause Unintended Complications. AB - To reduce the risk of catheter-associated urinary tract infection (CAUTI), limiting use of indwelling catheters is encouraged with alternative collection methods and early removal. Adverse effects associated with such practices have not been described. We also determined if CAUTI preventative measures increase the risk of catheter-related complications. We hypothesized that there are complications associated with early removal of indwelling catheters. We described complications associated with indwelling catheterization and intermittent catheterization, and compared complication rates before and after policy updates changed catheterization practices. We performed retrospective cohort analysis of trauma patients admitted between August 1, 2009, and December 31, 2013 who required indwelling catheter. Associations between catheter days and adverse outcomes such as infection, bladder overdistention injury, recatheterization, urinary retention, and patients discharged with indwelling catheter were evaluated. The incidence of CAUTI and the total number of catheter days pre and post policy change were similar. The incidence rate of urinary retention and associated complications has increased since the policy changed. Practices intended to reduce the CAUTI rate are associated with unintended complications, such as urinary retention. Patient safety and quality improvement programs should monitor all complications associated with urinary catheterization practices, not just those that represent financial penalties. PMID- 27657582 TI - Evolution of Laparoscopic Surgery for Colorectal Cancer: The Impact of the Clinical Outcomes of Surgical Therapy Group Trial. AB - The Clinical Outcomes of Surgical Therapy Group (COST) Trial established laparoscopic procedures offer short-term benefits while preserving the same oncologic outcomes in colorectal cancer (CRC) patients compared with open procedures. The aim of this study was to evaluate the trend of laparoscopic resection for CRC before and after the publication of the COST Trial. Retrospective study of surgically treated CRC patients was conducted from January 2000 to December 2009. Surveillance, Epidemiology, and End Results Program and Medicare. Between 2000 and 2009, 147,388 patients underwent resection for CRC, 9,901 resections were performed laparoscopically. In 2000, 1.0 per cent of colorectal resections were performed laparoscopically. There was a dramatic increase in laparoscopic resections in 2009 to 30.4 per cent. During this time period, rates of laparoscopic resections increased for all tumor stages. Right colectomies and early stage tumors had the most significant rise from 3.1 per cent (2004) to 38.7 per cent (2009) and 4.41 per cent (2004) to 39.17 per cent (2009), respectively; whereas, rectal and later stage tumors resection rates were more modest from 2.1 per cent (2004) to 13.2 per cent (2009) and 1.41 per cent (2004) to 17.10 per cent (2009), respectively. This study demonstrates the COST Trial had a significant impact on utilization of laparoscopic colorectal resection for CRC. Although laparoscopic colorectal resections have been accepted for all types of CRCs, more difficult procedures are being adopted at slower rates. PMID- 27657583 TI - Sonographic Appearance Is Useful in Predicting the Extent of Initial Operative Therapy for Thyroid Nodules Classified as "Suspicious for Malignancy". AB - The "suspicious for malignancy" (SFM) category of the Bethesda system for reporting thyroid cytopathology predicts an incidence of malignancy from 60 to 75 per cent. Recommended treatment is via either lobectomy or total/near total thyroidectomy. Identification of predictors of malignancy in this category would be useful in selecting the extent of operative therapy in these patients. Published literature has suggested that suspicious ultrasound (US) findings are useful in predicting malignancy in both the "benign," "atypia of uncertain significance/follicular lesion of uncertain significance," and "suspicious for follicular neoplasm" categories. We hypothesized that US would be similarly useful in patients with nodules classified as SFM. We performed a retrospective analysis of patients with fine needle aspiration biopsy (FNAB) classified as SFM who underwent thyroidectomy from October 2007 to October 2012. Data collected included symptoms, suspicious imaging findings, FNAB results, and histopathology results-all obtained via chart review. Findings were compared between patients with/without a diagnosis of thyroid malignancy. Significance was set at P < 0.05. Of 3839 FNAB, 53 were classified as SFM. Of these, 36 were available for review. Twenty-four (66.7%) carcinomas were identified-19 papillary, 3 follicular variant of papillary, 1 follicular, and 1 medullary. No symptoms/signs reached significance as a predictor of malignancy. A suspicious US appearance, however, was significantly associated with an underlying carcinoma (P = 0.002). Patients with a Bethesda system for reporting thyroid cytopathology report of SFM and suspicious US findings are statistically more likely to harbor an underlying malignancy. This information is useful in selecting which patients are most likely to benefit from total/near total thyroidectomy as opposed to lobectomy as the initial operative strategy. PMID- 27657584 TI - Discharge with Pancreatic Fistula after Pancreaticoduodenectomy Independently Predicts Hospital Readmission. AB - Readmission rates after pancreaticoduodenectomy (PD) are among the highest of any surgical procedure. The purpose of this study was to identify those factors present at discharge that may predict readmission after PD. All patients undergoing PD between 2010 and 2015 at a very high (>35 PD/year) volume center were entered into a prospective database. Twenty factors present at discharge from index admission identified on univariate analysis were subjected to multivariate analysis to identify those independently predictive of 30-day hospital readmission. A total of 220 patients underwent PD during the study period, 88 per cent of which had cancer. Mean age was 64.4 +/- 11.7 years with slight male preponderance (54.5%) and significant African American representation (33.2%). Surgical complications occurred in 67.3 per cent of patients the most common of which included infectious/leak (30%), gastrointestinal (29%), cardiorespiratory (13%), other (13%), minor complications (7%), multi system failure (5%), and new onset diabetes (3%). The 30-day readmission rate was 27.3 per cent and was due to infection (89%), failure to thrive (32%), nausea/vomiting (15%), or other (15%). On multivariate analysis, presence of pancreatic leak/fistula at discharge was the only significant predictor of readmission, present in 62.5 per cent of all readmitted patients (P = 0.001). Comorbidities, length of stay, insurance status, obesity, smoking, and discharge to a care venue other than home did not predict readmission. Patients manifesting pancreatic fistula after PD are at high risk for hospital readmission. Enhanced scrutiny regarding suitability for discharge should be exercised in these patients and measures taken to minimize readmission whenever possible. PMID- 27657585 TI - Excessive Postoperative Fluid Administration in Infants with Gastroschisis. AB - Careful fluid management is a cornerstone of neonatology because the cardiovascular, respiratory, and gastrointestinal systems in the newborn are sensitive to overhydration. Fluid management in gastroschisis is complicated by insensible fluid loss and postoperative third-space fluid shifts. Study of perioperative fluid management in gastroschisis is limited and has not undergone careful scrutiny. We reviewed perioperative fluid administration and urine output in all infants with gastroschisis over a 5-year period. Data included whether the patient underwent primary closure or staged repair, weight, and events during hospitalization (length of hospitalization and duration of gastric decompression, parenteral nutrition, and ventilator support). Paired t test gave statistical comparisons with significance at P < 0.05. From 2010 to 2014, 24 patients underwent abdominal closure, 17 had primary and 7 had staged closures. Fluid administration exceeded 100 mL/kg/d after primary closure, and was significantly higher (>150 mL/kg/d; P < 0.05) after staged closure on postoperative days 0 to 5. Postoperative urinary output exceeded 75 mL/kg/d for all patients, with higher volumes reaching 100 mL/kg/d after staged closure on postoperative days 4 to 6 (P < 0.05). Two patients died of sepsis. All survivors were discharged with intestinal continuity and gaining weight on oral feeding. Patients with gastroschisis received large volumes of fluid after operation despite similarly high urine output and positive daily fluid balances. The amounts of fluid administered after both primary and staged closure may be excessive and potentially deleterious. PMID- 27657586 TI - Can Abdominal Wall Reconstruction Be Safely Performed Without Drains? AB - The use of closed suction drains in the abdominal wall is a common practice in abdominal wall reconstruction (AWR) operations. Drains can be a conduit for bacteria and can cause pain and discomfort for patients after surgery. A single hernia program has implemented the principles of clinical quality improvement in an attempt to improve outcomes for hernia patients. An attempt at a process improvement was implemented to eliminate the use of drains in AWR by adapting the technique. A total of 102 patients undergoing AWR were included between 8/11 and 9/15 (49 months). Compared with the group before the attempt at eliminating the use of abdominal wall drains (8/11-9/13), the group of patients after the implementation of the attempted process improvement (9/13-9/15) had less wound and pulmonary complications, a shorter hospital stay, less time in the postanesthesia care unit, and less opioid use in the postanesthesia care unit as well as for the entire hospital stay. In this group of AWR patients, an attempt at process improvement that eliminated the use of drains led to improved outcomes. Abdominal wall drains may be able to be safely eliminated with appropriate technique adaptation for AWR. PMID- 27657587 TI - The Impact of Chemotherapy on Complications Associated with Mastectomy and Immediate Autologous Tissue Reconstruction. AB - We performed this study to evaluate the impact of chemotherapy on the outcomes associated with immediate autologous tissue reconstruction (IATR) in the treatment of breast cancer. Patients were divided into two groups: Group 1 received chemotherapy before surgery and Group 2 did not receive chemotherapy. Records were reviewed to identify demographics, comorbidities, histology, and wound healing complications. Groups were compared using Kruskal-Wallis and Fisher exact tests as appropriate. A total of 128 patients were identified: 29 received chemotherapy before surgery (Group 1) and 99 did not receive chemotherapy (Group 2). Group 1 patients were more likely to have diabetes 27 per cent versus 6 per cent (P = 0.005) despite both groups having a mean body mass index of 30. Group 2 patients had less advanced stage disease as expected because they did not receive chemotherapy; 37 per cent of Group 2 patients had stage 0 breast cancer (P < 0.001). The incidence of wound complications was 17 per cent in Group 1 and 12 per cent in Group 2 (P = NS). Preoperative chemotherapy for breast cancer followed by IATR was associated with no increased risk of healing complications. IATR can be offered to patients who require preoperative chemotherapy, and their healing will not be impaired as a result of the chemotherapy. PMID- 27657589 TI - Robotic Transhiatal Esophagectomy in a Community Hospital: Evolution of Technique. AB - Esophageal cancer is an uncommon but highly lethal disease. Surgical resection is the gold standard of treatment for early-stage disease. Traditional surgical approach entailed significant convalescence, hospital stay, and morbidity and mortality. Transhiatal esophagectomy (THE) involves blind dissection of the esophagus with minimal mediastinal lymphadenectomy. Integration of robotic surgery is an alternate platform for minimally invasive approach while maintaining safety and following oncologic principles. We review our technique for minimally invasive THE using robotic technology, demonstrating the safety and efficacy of robotic technology surgery. We present a retrospective review of a single surgeon's data of patients treated with robotic-assisted THE, with a chart review to evaluate pathology, adequacy of surgical resection, nodal harvest, and perioperative course. Robotic THE (rTHE) shows promise as a valid option for esophageal resection, including premalignant and advanced stages of cancer. Adequate transhiatal mediastinal nodal resection can be performed with the robot. PMID- 27657588 TI - Perioperative Statin Treatment: Can It Decrease Postsurgical Cardiac Event Risk in Noncardiac Surgery? AB - Cardiac events are an important cause of postsurgical morbidity and mortality. Statin drugs have been studied as potentially risk-modifying agents in perioperative medicine. They have been shown to confer a protective benefit in cardiac surgery, but the evidence available in noncardiac surgery patient populations remains less conclusive. We hypothesized that perioperative statin treatment would be associated with lower incidence of postsurgical cardiac events (PSCEs) after major noncardiac surgery. A retrospective cohort study included 21,637 major noncardiac surgeries. Statin treatment was the exposure of interest and PSCE was the primary outcome measure. Data collection included patient age, body mass index, smoking status, diabetic status, cardiac event history, statin treatment history, and PSCE diagnoses. Perioperative statin treatment occurred in 4176 cases (19.3%). PSCEs occurred in 50 cases (0.23%), 29 in the untreated control group (0.17%) and 21 in the statin treatment group (0.50%). Relative risk in the untreated group was 0.3303 (95% confidence interval = 0.1886, 0.5786). This implied that statin-treated patients had higher risk than the untreated group. However, a logistic regression model that accounted for observed cardiac disease risk factors showed statin treatment not to be a significant predictor of PSCE in this sample. Analysis repeated in high-risk subsets of the cohort yielded similar results. A propensity score matching method that minimized differences between study groups also failed to demonstrate a significant association between statin treatment and PSCE risk. Our study did not demonstrate a significant association between perioperative statin treatment and PSCEs after major noncardiac surgery. PMID- 27657590 TI - Diabetic Foot Ulcers: The Importance of Patient Comorbidity Recognition and Total Contact Casting in Successful Wound Care. AB - Diabetic foot ulcers (DFUs) are a major burden on the health-care system. The purpose of this study is to investigate factors affecting the healing rate of DFU in a university wound care center. Records of DFU patients treated between July 2013 and February 2015 were reviewed. Demographics, comorbidities, wound characteristics, and treatment modalities including offloading, hyperbaric oxygen treatment, total contact casting, and bioengineered skin were investigated. All patients underwent weekly debridement regardless of treatment modality. A total of 114 patients ages 18 to 98 comprised the study population. Total contact casting was the only treatment associated with increased healing (P = 0.02). Smoking (P = 0.004) and deep vein thrombosis history (P = 0.001) significantly decreased the likelihood of wound healing. Patients with past vascular event trended toward longer healing times (P = 0.07). Total contact casting in combination with weekly wound debridement showed benefit in DFU wound healing, whereas patients with a history of deep vein thrombosis and smoking were less likely to heal. PMID- 27657592 TI - Impact of Bariatric Surgery on Hiatal Hernia Repair Outcomes. AB - Large hiatal hernias are notorious for their high recurrence rates after conventional repair. Recurrence rates have been described to be higher in obese patients due to increased intra-abdominal pressure. We hypothesized that patients who undergo hiatal hernia repair (HHR) with bariatric surgery (BAR) will have a lower hernia recurrence rate when compared to patients who undergo HHR with fundoplication (FP) due to the decrease in intra-abdominal pressure observed with weight loss. This was an Institutional Review Board approved retrospective review. The outcomes of patients who underwent HHR+BAR as well as patients who had HHR+FP only from 2007 to 2014 were reviewed. Patients who had small hiatal hernias (<2 cm), underwent an anterior repair, or had gastropexy only were excluded. The primary outcome was hernia recurrence and reflux resolution. The outcomes of 58 patients who had HHR+BAR were compared with 30 patients with HHR+FP. Hernia recurrence rate for HHR+BAR was 12 per cent, whereas hernia recurrence rate for HHR+FP was 38 per cent (P < 0.01). Reflux resolution for HHR+FP was 78 per cent, whereas reflux improvement rate for HHR+BAR was 84 per cent (P = n.s.). Combining HHR with BAR leads to a lower hernia recurrence rate when compared to patients who undergo HHR with FP. PMID- 27657591 TI - Indications for Surgical Resection in Low-Grade Pancreatic Neuroendocrine Tumors. AB - The role of surgical resection in low-grade pancreatic neuroendocrine tumors (P NET) is unclear. The patients diagnosed with low-grade P-NET from 1988 to 2012 were identified in SEER. Five hundred and sixty-one patients met the inclusion criteria. A majority were white (82.9%), and node negative (69.9%). Univariate analysis revealed that tumor size (<2 cm 8.3%, 2-4 cm 38.5%, and >4 cm 40.3%; P < 0.0001) and surgery (30.9% vs 25.3%; P = 0.0014) were associated with the risk of lymph node metastases (LNM). In contrast, age (P = 0.8360), gender (P = 0.4903), and race (P = 0.4235) were not. Five-year disease-free survival was associated with size (<2 cm 89.4%, 2-4 cm 80.0%, and >4 cm 74.5%; P = 0.0089), LNM (72.4% vs 82.9%; P = 0.0025), and surgery (84.3% vs 47.5%; P < 0.0001). Cox regression model showed that the association with LNM (P = 0.0025) and surgery (P < 0.0001) was significant. Surgery was associated with an improved disease-free survival for tumors >2 cm (2-4 cm, 84.4% vs 26.0% at five years; P = 0.0003, and >4 cm, 80.5% vs 49.5% at five years; P < 0.0001) but not for those with tumor size <2 cm (P = 0.4525). In conclusions, low-grade P-NETs in patients with tumor size >2 cm showed an increased risk of LNM and improved survival with resection. PMID- 27657595 TI - Verve, vision and vitality. AB - A new report from the Kings Fund raises questions over the ability of nurses to take on leadership positions. Nursing, it says, needs people who can 'inspire, move, energise and enthuse others'. They're wonderful words, enough in themselves to exorcise the lethargy and apathy that has taken hold of nurse managers. It's a sort of 'get up and go' report, full of glorious adjectives that one could only wish applied to NHS leaders - not just nurses. PMID- 27657593 TI - Factors Associated with Persistently Positive Margin Status after Breast Conserving Surgery in Women with Breast Cancer: An Analysis of the National Cancer Database. AB - Margin status after definitive breast-conserving surgery (BCS) is a key predictor of local tumor recurrence. This study utilized the National Cancer Database, which captures 70 per cent of all cancer cases nationally, to determine factors associated with persistently positive margins status post-BCS. From 1998 to 2010, there were 1,170,284 patients with stage 0 to 3 breast cancer who underwent BCS. After final definitive surgery, 7.3 per cent of patients had positive margins. On bivariate analysis, persistently positive margin status post-BCS was correlated with patient age, race, ethnicity, comorbidities, facility type and location, tumor size, grade, presence of invasive disease, lymph node positivity, as well as receipt of neoadjuvant chemotherapy and adjuvant radiation therapy (P < 0.001). On multivariate analysis, patients who were black, with multiple comorbidities, living in a Pacific state, who had larger, high-grade, node positive invasive tumors, who did not receive neoadjuvant chemotherapy, and who did not receive adjuvant radiation therapy were more likely to have persistently positive margins (P < 0.05). Although the goal of BCS is the attainment of negative margins, 7.3 per cent of patients have persistently positive margins after definitive surgery. These patients tend to have more aggressive disease and greater comorbidities, and are less likely to receive adjuvant radiation therapy. PMID- 27657594 TI - Appendicitis in Diabetics: Predictors of Complications and Their Incidence. AB - Appendicitis is the most common surgical emergency encountered by the general surgeon. Literature has demonstrated that diabetics may manifest atypical signs of infection, often clouding the diagnostic picture. We conducted a 3-year retrospective analysis of adults with appendicitis to determine differences in presentation, diagnosis, treatment, and outcomes for diabetic versus nondiabetic patients. Demographics, symptoms, imaging, procedure(s), complications, and length of stay (LOS) were obtained via chart review. Factors were compared between patients with and without diabetes using chi-squared test, t test, or Mann-Whitney U test (significance at P <= 0.05). Multivariate regression analysis identified variables predicting longer LOS or perforation at diagnosis. Overall, 339 patients met inclusion criteria [303 were nondiabetic (ND), 36 were diabetic (D)]. On univariate analysis, diabetics were more likely to have other comorbid illnesses: obesity (P < 0.001), chronic kidney disease (P = 0.003), hypertension (P < 0.001), coronary artery disease (P < 0.001), peripheral vascular disease (PVD, P = 0.31), and chronic obstructive pulmonary disease (P = 0.002). Diabetics presented with lower white blood cell counts (mean 14.2 ND, 11.9 D, P = 0.02), and were more likely to present with perforation (18.5% ND, 38.9% D, P = 0.008). LOS was longer in diabetics (1.0 day for ND, 3.0 day for D, P < 0.001). Complications were more frequent in diabetics (19.4% D vs 8.6% ND), which trended toward but failed to reach significance (P = 0.066). On multivariate analysis, however, old age was the only characteristic associated with perforation [odds ratio: 1.05 (1.02-1.06), P < 0.001], whereas diabetes, chronic obstructive pulmonary disease, and older age predicted longer LOS (P <= 0.001). Diabetics present a more complicated clinical picture having significantly more comorbidities and a trend toward postoperative complications necessitating a higher index of suspicion to detection complications. Further study is needed to evaluate the optimal diagnostic and management approach in this challenging population. PMID- 27657596 TI - Prescribing is 'not priority' this year. AB - The government's decision to shelve nurse prescribing has caused confusion in the profession, it emerged last week amid growing concern that Health Secretary Virginia Bottomley has still not set a new date for the start of the scheme. PMID- 27657598 TI - Call for ban on tobacco adverts. AB - The UK Central Council has called on the government to ban tobacco advertising. PMID- 27657597 TI - Policymakers leave nurses 'struggling for identity'. AB - A shortage of leaders with vision and authority in British nursing has left nurses struggling to establish a role and identity for themselves in a changing NHS, says a report from the King's Fund Centre. PMID- 27657599 TI - Regions under pressure to answer student job crisis. AB - The NHS Management Executive is pressing regions for answers to the crisis of student nurses qualifying without jobs. PMID- 27657600 TI - Rise in number of prison nurses. AB - The Nursing Service for Prisoners (NSP) is to increase the number of qualified nurses working in jails and will use specialist NHS staff to help meet prisoners' health care needs. PMID- 27657602 TI - MSF may take in practice nurses. AB - The Health Visitors' Association parent union, MSF, is considering setting up a new professional section for practice nurses. PMID- 27657603 TI - Midwife-led units win government support. AB - Midwives have welcomed a government report that backs the continued development of midwife-led maternity units. PMID- 27657605 TI - Whitley pay rising above private rates. AB - NHS nurses' Whitley pay has now overtaken average independent hospital salaries, a leaked pay Review Body report has revealed. PMID- 27657604 TI - Child care registration rules relaxed. AB - Nurses unions have condemned new health department guidelines relaxing child care registration regulations. PMID- 27657606 TI - Primary health staff squeeze. AB - Community nursing services may face greater workloads after community care reforms come into force in April, the nurse member of the government's Community Care Support Force has warned. PMID- 27657607 TI - New directory lists 2,000 sources of support. AB - A comprehensive directory containing more than 2,000 sources of help and information on health-related problems was launched in London last week. PMID- 27657609 TI - Warning of future catastrophe in NHS. AB - Pressure on hospital beds in North East Thames has forced districts to accept urgent admissions only, prompting warnings of a future catastrophe in the capital's health services. PMID- 27657610 TI - CPNs up by 250 per cent. AB - The number of community psychiatric nurses in England has increased by almost 250 per cent over the past ten years. PMID- 27657612 TI - Government to back legal changes in drugs licensing. AB - The government has promised to back changes in the law which would give nurses and doctors far more information about medicines. PMID- 27657611 TI - Mental Health Act review is inadequate, says Labour. AB - Community supervision orders for mentally ill people will be at the core of the health department's review of the Mental Health Act. PMID- 27657615 TI - ? AB - A series of quality road shows was launched last week by Department of Health Chief Nursing Officer Yvonne Moores. The 13 regional events aim to spread ideas about improving the quality of care. Speaking in Liverpool, Mrs Moores said the NHS reforms 'will be judged not only by their ability to treat more patients but by the quality of care patients receive.' A book and training pack on quality are available from Elaine Taylor- Whilde, Room 4N.34B, Doll, Quarry House, Quarry Hill, Leeds LS2 7UE. PMID- 27657613 TI - 170,000 health professionals suffer from mental illness. AB - Up to 170,000 nurses, doctors and other health service staff suffer from mental illness each year, Health Secretary Virginia Bottomley said last week. PMID- 27657616 TI - Special commemorative service for pioneer in nursing research. AB - A special memorial service was held last week to commemorate the life of leading nurse researcher, Pam Hawthorn who died earlier this month from multiple sclerosis. One of the first nurses to earn a PhD, Ms Hawthorn was noted for her research in the areas of strokes, pressure sores and education. She is credited as being among the leading campaigners to put nursing research on the map in the 1970s and was active in the Royal College of Nursing's research society. She retired from her post as Director of Nursing Studies at the University of Nottingham in the mid-Eighties when she was diagnosed as having multiple sclerosis. Tom Keighley, former RCN research adviser, now Regional Nursing Officer for Yorkshire, described her as a pathfinder'. PMID- 27657617 TI - ? AB - Winners of the 1992 Health Visitors' Association/Crookes Healthcare National Health Visiting Week awards received their prizes of L250 at a ceremony in London last week. Left to right are: Mair Jones with Gwynedd winner Catrin Evans; Alan Rosome, Head of Marketing at Crookes Healthcare; Gail Ewing and Cambridge winner Rona Thorogood; and Belfast winner Phelim Quinn. PMID- 27657618 TI - Health needs homelessness. AB - Nurses should be trained to deal with the specific problems of homeless people, says a recent report by Yorkshire Region. PMID- 27657619 TI - Canada: Alcohol warning issue dodged. AB - The Canadian federal government has dodged a Commons Committee recommendation that alcohol bottles should carry warnings about the dangers of drinking during pregnancy. PMID- 27657621 TI - US: Nurse takes seat in Congress. AB - Nursing history was made when Texan Democrat Eddie Bernice Johnson took her seat in the US Congress. PMID- 27657620 TI - Germany: hospital food is 'unhealthy'. AB - Food in some German hospitals is bad for patients' health, the President of the German Nutrition Association, Professor Peter Schauder, has claimed. PMID- 27657622 TI - Student quotas are still not established. AB - With just three months to go before they take responsibility for funding nurse training, only one health region has been able to provide details of how many new students will be needed next year, the English National Board heard last week. PMID- 27657623 TI - DNs may be failing in assessing patient needs. AB - District nurses may be failing to assess the needs of severely physically disabled adults living in the community, according to a study in the British Medical Journal. PMID- 27657625 TI - Monitoring unnecessary caesarean births. AB - A monitoring system which measures oxygen levels in babies' blood during labourmay cut the number of Ceasarean sections performed each year, and could help explain how and why some babies become brain-damaged. PMID- 27657624 TI - ? AB - High levels of natural light are a feature of the new L30 million Salisbury District Hospital, designed after consultation with patients and staff. It includes a rehabilitation department with hydrotherapy pool and an elderly care unit. PMID- 27657626 TI - Emergency services for coronary care. AB - Accident and Emergency departments should be equipped to administer thrombolysis, a study by researchers at Newcastle's Freeman Hospital has recommended. PMID- 27657627 TI - Hypertension and birth weight linked to fetal life. AB - The relation between high blood pressure and low birth weight is initiated in fetal life, research suggests. PMID- 27657628 TI - Substance abuse part of trauma screening. AB - Assessment and intervention for substance abuse should be a routine component of trauma admission screening, nursing researchers suggest. PMID- 27657629 TI - Beneficial effects of 'overprotection'. AB - 'Overprotection' by family and friends might prove beneficial to the psychosocial adjustment of patients following myocardial infarction. PMID- 27657630 TI - Inheritance may be a factor in bowel disease. AB - A major dominant gene has a role in ulcerative colitis and a major recessive gene in Crohn's disease, new research suggests. PMID- 27657631 TI - Genetic defect found in heart condition. AB - Hypertrophic cardiomyopathy, the condition which led to the death of football manager Terry Yorath's son, is genetically determined and can be identified by a blood test. PMID- 27657632 TI - Could do better? AB - Only three out of 29 university departments have carried out nursing research of national excellence, according to a recent assessment exercise. Daniel Allen reports on the findings. PMID- 27657633 TI - No room for beginners. AB - When disaster strikes, be it natural or man made, one of the first agencies on the scene is Medecins sans Frontieres (MSF). Demand for its help has never been greater, and the organisation is now recruiting from the UK. PMID- 27657634 TI - Stopping them from starting. AB - Despite the Health of the Nation's target to reduce smoking, the government continues to resist a cigarette advertising ban on the grounds of 'commercial freedom of speech'. Graham Scott reports. PMID- 27657635 TI - Correcting the wrong impression. AB - I would like to correct an impression that may have been given by Linda Sbaih in her article, Mental Health Act: detention in A&E (Clinical, January 6). PMID- 27657636 TI - Tired of Sister Susie's jibes at NVQs. AB - While I appreciate that the Sister Susie column is written tongue in cheek, it seems to me sad that she makes constant jibes at staff who have obtained NVQ certificates. PMID- 27657637 TI - Directives could stop back injuries. AB - New EC directives on the manual handling of loads could stop district nurses being the professional discipline most prone to back injury - if they stand up for their rights. PMID- 27657638 TI - Dynamic situations in private nursing. AB - What a pity it was that the author of 'A private home with no brick walls '(Letters, January 6) saw fit to withhold her name and address. PMID- 27657639 TI - Exercising caution on public endorsing. AB - I come from a conventional pro- fluoridation background, and am the daughter and wife of dental surgeons. PMID- 27657640 TI - Information exchange. AB - * I am interested in the development of nurse education and would like to hear from student nurses and tutors participating in Project 2000. PMID- 27657641 TI - Developments in community nursing. AB - While your November 11 news item detailed a Royal College of Nursing survey showing 'broad cuts in the school nurse service', I would like to tell you of the developments in our service. PMID- 27657644 TI - Nurses, Computers and Information Technology P MProcter Nurses, Computers and Information Technology Chapman & Hall 106pp L10.95 0-412-334-50-X [Formula: see text]. AB - 'Present-day society' - to quote the author of Nurses, Computers and Information Technology - is moving faster technologically than any other previous age. PMID- 27657642 TI - Child Studies: The First Year. AB - Child Studies I: The First Year is the first in a series of child development studies which range from birth to five years. Sections include: From birth; From 1 month; From 3 months; and From 9 months. The studies show several children in each age group progressing in their home environment. The families are of varied race and culture. PMID- 27657645 TI - End note. AB - The royal family has borne the brunt of much criticism over the past year and one must have a degree of sympathy for them. They are held up as such great pillars of virtue, - although they have played their part in creating this image. PMID- 27657646 TI - Listings. PMID- 27657647 TI - Diamagnetic Imaging Agents with a Modular Chemical Design for Quantitative Detection of beta-Galactosidase and beta-Glucuronidase Activities with CatalyCEST MRI. AB - Imaging agents for the noninvasive in vivo detection of enzyme activity in preclinical and clinical settings could have fundamental implications in the field of drug discovery. Furthermore, a new class of targeted prodrug treatments takes advantage of high enzyme activity to tailor therapy and improve treatment outcomes. Herein, we report the design and synthesis of new magnetic resonance imaging (MRI) agents that quantitatively detect beta-galactosidase and beta glucuronidase activities by measuring changes in chemical exchange saturation transfer (CEST). Based on a modular approach, we incorporated the enzymes' respective substrates to a salicylate moiety with a chromogenic spacer via a carbamate linkage. This furnished highly selective diamagnetic CEST agents that detected and quantified enzyme activities of glycoside hydrolase enzymes. Michaelis-Menten enzyme kinetics studies were performed by monitoring catalyCEST MRI signals, which were validated with UV-vis assays. PMID- 27657648 TI - Tilt series STEM simulation of a 25*25*25nm semiconductor with characteristic X ray emission. AB - The detection and quantification of fabrication defects is vital to the ongoing miniaturization of integrated circuits. The atomic resolution of HAADF-STEM combined with the chemical sensitivity of EDS could provide the means by which this is achieved for the next generation of semiconductor devices. To realize this, however, a streamlined acquisition and analysis procedure must first be developed. Here, we report the simulation of a HAADF-STEM and EDS tilt-series dataset of a PMOS finFET device which will be used as a testbed for such a development. The methods used to calculate the data and the details of the specimen model are fully described here. The dataset consists of 179 projections in 2 degrees increments with HAADF images and characteristic X-ray maps for each projection. This unusually large calculation has been made possible through the use of a national supercomputer and will be made available for the development and assessment of reconstruction and analysis procedures for this highly significant industrial application. PMID- 27657649 TI - StatSTEM: An efficient approach for accurate and precise model-based quantification of atomic resolution electron microscopy images. AB - An efficient model-based estimation algorithm is introduced to quantify the atomic column positions and intensities from atomic resolution (scanning) transmission electron microscopy ((S)TEM) images. This algorithm uses the least squares estimator on image segments containing individual columns fully accounting for overlap between neighbouring columns, enabling the analysis of a large field of view. For this algorithm, the accuracy and precision with which measurements for the atomic column positions and scattering cross-sections from annular dark field (ADF) STEM images can be estimated, has been investigated. The highest attainable precision is reached even for low dose images. Furthermore, the advantages of the model-based approach taking into account overlap between neighbouring columns are highlighted. This is done for the estimation of the distance between two neighbouring columns as a function of their distance and for the estimation of the scattering cross-section which is compared to the integrated intensity from a Voronoi cell. To provide end-users this well established quantification method, a user friendly program, StatSTEM, is developed which is freely available under a GNU public license. PMID- 27657650 TI - Experience facilitates the emergence of sharing behavior among 7.5-month-old infants. AB - Given the centrality of prosociality in everyday social functioning, understanding the factors and mechanisms underlying the origins of prosocial development is of critical importance. This experiment investigated whether experience with reciprocal object exchanges can drive the developmental onset of sharing behavior. Seven-month-old infants took part in 2 laboratory visits to assess their sharing behavior and ability to release objects. During the intervening 7- to 14-day period parents led infants in an intervention in which they were either encouraged to release objects into a container (bucket condition, n = 20), or share objects with the parent in the context of reciprocal object exchanges (sharing condition, n = 20). Results showed that infants in the sharing condition shared significantly more than infants in the bucket condition following the intervention, and infants in the sharing condition significantly increased their sharing behavior across the 2 visits. Parental empathy moderated the effect of this sharing intervention, but frequency of practice did not. These results suggest that reciprocal turn-taking in dyadic object-exchange interactions may facilitate the early emergence of sharing behavior, and this effect is mediated by parental empathy. (PsycINFO Database Record PMID- 27657651 TI - Autoimmune hemolytic anemia (AIHA) associated with chronic lymphocytic leukemia in the current era of targeted therapy. AB - In the past decade the introduction of targeted therapies has dramatically transformed the landscape of treatment for chronic lymphocytic leukemia (CLL). Whether this new therapeutic scenario will modify the current prevalence statistics and natural history of autoimmune cytopenias complicating CLL is still a matter of debate. Here we present a comprehensive review of the literature on this topic, with special emphasis on the incidence of autoimmune hemolytic anemia (AIHA). The potential to induce autoimmune cytopenia has been studied mostly with ibrutinib, a first- in-class bruton kinase (BTK) inhibitor, licensed for the treatment of relapsed/refractory high-risk CLL. Recent observations suggest that emergent AIHA occurring during therapy with ibrutinib is more an expression of CLL activity than an ibrutinib-mediated process. Since available information on AIHA occurring during and after therapy with small-molecule kinase inhibitors relies mainly on data collected from clinical trials, a close post- marketing surveillance is mandatory in order to improve our understanding of this topic. PMID- 27657653 TI - Supportive behaviors in adolescent romantic relationships moderate adrenocortical attunement. AB - This study investigated dyadic adrenocortical attunement within adolescent romantic relationships. An ethnically diverse sample (42% Latino) of adolescent heterosexual dating couples (N=91 dyads, Mage=16.5 years, SD=0.99) donated eight saliva samples (later assayed for cortisol) over the course of a 3-h laboratory session. Supportive behaviors were coded during a conflict and jealousy interaction task from video recordings, and participants completed pre-and-post task questionnaires. Parallel process latent growth models revealed a strong positive association between the couples' cortisol intercept, indicating that couples show attunement in initial levels of cortisol. Further, observed supportive behavior moderated the strength of the association between dyadic cortisol slopes. The results imply that low levels of supportive behavior predicted stronger adrenocortical attunement in the change in cortisol levels over time between adolescent romantic partners. These findings indicate that even early romantic relationships exhibit coordination of physiological activity. Findings raise the possibility that adrenocortical attunement may be a dyadic pathway through which the proximal social context of early romantic relationships is translated into risk or resilience in health and behavior. PMID- 27657652 TI - Cost-effectiveness of obinutuzumab for chronic lymphocytic leukaemia in The Netherlands. AB - BACKGROUND: Obinutuzumab combined with chlorambucil (GClb) has shown to be superior to rituximab combined with chlorambucil (RClb) and chlorambucil (Clb) in newly diagnosed patients with chronic lymphocytic leukaemia (CLL). This study evaluates the cost-effectiveness per life-year and quality-adjusted life-year (QALY) of GClb compared to RClb, Clb, and ofatumumab plus chlorambucil (OClb) in The Netherlands. METHODS: A Markov model was developed to assess the cost effectiveness of GClb, RClb, Clb and other treatments in the United Kingdom. A country adaptation was made to estimate the cost-effectiveness of these therapies in The Netherlands using Dutch unit costs and Dutch data sources for background mortality and post-progression survival. RESULTS: An incremental gain of 1.06 and 0.64 QALYs was estimated for GClb compared to Clb and RClb respectively, at additional costs of ?23,208 and ?7254 per patient. Corresponding incremental cost effectiveness ratios (ICERs) were ?21,823 and ?11,344 per QALY. Indirect treatment comparisons showed an incremental gain varying from 0.44 to 0.77 QALYs for GClb compared to OClb and additional costs varying from ?7041 to ?5028 per patient. The ICER varied from ?6556 to ?16,180 per QALY. Sensitivity analyses showed the robustness of the results. CONCLUSION: GClb appeared to be a cost effective treatment strategy compared to RClb, OClb and Clb. PMID- 27657655 TI - Patulitrin and Acetyl Patulitrin, Flavonol Glycosides From Lagascea mollis. PMID- 27657654 TI - Fluorescence Immunoassay System via Enzyme-Enabled in Situ Synthesis of Fluorescent Silicon Nanoparticles. AB - The emergence of fluorescent nanomaterials with excellent performances has triggered the development of fluorescence analysis technique, which possesses several advantages in the research and clinical applications. However, current strategies for fluorescence immunoassay usually involve the routine fluorophore labeled antibody and/or awkward signal generation procedure that may not be available in conventional enzyme-linked immunosorbent assay (ELISA) systems. Herein, we circumvent this problem by imparting an exquisite signal generation mechanism to commercially available alkaline phosphatase (ALP)-based ELISA platform and putting forward a conceptual fluorescent ELISA system based on an original ALP-enabled in situ synthesis of fluorescent nanomaterials. After adding target antigen, the presence of ALP labeled on antibody catalyzes the transformation of the substrate ascorbic acid 2-phosphate into ascorbic acid. Then the resultant ascorbic acid (i.e., ascorbate) interacts with amine containing silane molecules (no fluorescence) to produce intense cyan fluorescent silicon nanoparticles. For the proof-of-concept, alpha-fetoprotein and human immunoglobulin G are chosen as the model antigen targets, and our proposed immunoassay (designated as the nanoparticles generation-based fluorescent ELISA) enables the detection with either fluorescence spectroscopy or naked-eye readout under the ultraviolet lamp. The convincing recognition mechanism and assay performance ensure fluorescent ELISA to quantitatively evaluate the alpha fetoprotein level in serologic test and potentially apply in the clinic diagnosis of hepatocellular carcinoma. PMID- 27657656 TI - The heat resistance and spoilage potential of aerobic mesophilic and thermophilic spore forming bacteria isolated from Chinese milk powders. AB - The propensity for aerobic bacilli and allied genera to produce highly heat resistant spores and thermally stable spoilage enzymes are major bacteriological issues faced by the dairy industry. Most of the enzymes are able to survive any heat treatment applied during the manufacture of milk powders and have the potential to remain active in milk powders and other dairy products during storage, and may explain some of the sensory and functionality defects reported in dairy products. Despite many reports on the occurrence of spore-forming bacteria in dairy products, knowledge about food quality related properties of many aerobic sporeformers is still scarce. Therefore, the aim of this study was to determine thermal resistance and spoilage potential of a large pool of mesophilic and thermophilic sporeformers, representing 738 isolates and 31 different RAPD groups, recently isolated from Chinese milk powders. Spore formers producing highly heat resistant spores (surviving 125 degrees C for 30min) included 2 thermophiles (Geobacillus thermoleovorans group and Geobacillus stearothermophilus) and one mesophilic species (Brevibacillus brevis). Paenibacillus macerans showed the highest proteolytic activity followed by members of the Bacillus cereus group, Br. brevis, Bacillus subtilis, G. thermoleovorans group and Virgibacillus proomii. The highest lipase producing strains belonged to Bacillus licheniformis. Phospholipase activity was only shown by members of the B. cereus group and Brevibacillus parabrevis. Ten strains showed positive beta-galactosidase activity, while, 4 strains showed positive haemolytic activity. B. licheniformis strains, despite belonging to one RAPD group or sub-group showed markedly different phenotypic characters which support the previous findings of heterogeneity in RAPD-based B. licheniformis groups. The results of this study will broaden the knowledge about the spoilage potential and thermal resistance of many strains of dairy origin. PMID- 27657657 TI - The potential of hybrid forward osmosis membrane bioreactor (FOMBR) processes in achieving high throughput treatment of municipal wastewater with enhanced phosphorus recovery. AB - Extensive research in recent years has explored numerous new features in the forward osmosis membrane bioreactor (FOMBR) process. However, there is an aspect, which is revolutionary but not yet been investigated. In FOMBR, FO membrane shows high rejection for a wide range of soluble contaminants. As a result, hydraulic retention time (HRT) does not correctly reflect the nominal retention of these dissolved contaminants in the bioreactor. This decoupling of contaminants retention time (CRT, i.e. the nominal retention of the dissolved contaminants) from HRT endows FOMBR a potential in significantly reducing the HRT for wastewater treatment. In this work, we report our results in this unexplored treatment potential. Using real municipal wastewater as feed, both a hybrid microfiltration-forward osmosis membrane bioreactor (MF-FOMBR) and a newly developed hybrid biofilm-forward osmosis membrane bioreactor (BF-FOMBR) achieved high removal of organic matter and nitrogen under HRT of down to 2.0 h, with significantly enhanced phosphorus recovery capacities. In the BF-FOMBR, the used of fixed bed biofilm not only obviated the need of additional solid/liquid separation (e.g. MF) to extract the side-stream for salt accumulation control and phosphorus recovery, but effectively quarantined the biomass from the FO membrane. The absence of MF in the side-stream further allowed suspended growth to be continuously removed from the system, which produced a selection pressure for the predominance of attached growth. As a result, a significant reduction in FO membrane fouling (by 24.7-54.5%) was achieved in the BF-FOMBR due to substantially reduced bacteria deposition and colonization. PMID- 27657658 TI - Assessing the phototransformation of diclofenac, clofibric acid and naproxen in surface waters: Model predictions and comparison with field data. AB - Phototransformation is important for the fate in surface waters of the pharmaceuticals diclofenac (DIC) and naproxen (NAP) and for clofibric acid (CLO), a metabolite of the drug clofibrate. The goal of this paper is to provide an overview of the prevailing photochemical processes, which these compounds undergo in the different conditions found in freshwater environments. The modelled photochemical half-life times of NAP and DIC range from a few days to some months, depending on water conditions (chemistry and depth) and on the season. The model indicates that direct photolysis is the dominant degradation pathway of DIC and NAP in sunlit surface waters, and potentially toxic cyclic amides were detected as intermediates of DIC direct phototransformation. With modelled half life times in the month-year range, CLO is predicted to be more photostable than DIC or NAP and to be degraded mainly by reaction with the *OH radical and with the triplet states of chromophoric dissolved organic matter (3CDOM*). The CLO intermediates arising from these processes and detected in this study (hydroquinone and 4-chlorophenol) are, respectively, a chronic toxicant to aquatic organisms and a possible carcinogen for humans. Hydroquinone is formed with only ~5% yield upon CLO triplet-sensitised transformation, but it is highly toxic for algae and crustaceans. In contrast, the formation yield of 4 chlorophenol reaches ~50% upon triplet sensitisation and ~10% by .OH reaction. The comparison of model predictions with field data from a previous study yielded a very good agreement in the case of DIC and, when using 4-carboxybenzophenone as proxy for triplet sensitisation by CDOM, a good agreement was found for CLO as well. In the case of NAP, the comparison with field data suggests that its direct photolysis quantum yield approaches or even falls below the lower range of literature values. PMID- 27657660 TI - Discovery of novel targets for antivirals: learning from flies. AB - Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals. In addition, functional screens revealed conserved host factors required for efficient viral translation, such as the ribosomal protein RACK1 and the release factor Pelo. These proteins are promising candidates for host-targeted antivirals. PMID- 27657661 TI - Choosing an Important Project: Take Two. PMID- 27657659 TI - Viral evasion and challenges of hepatitis C virus vaccine development. AB - Hepatitis C virus (HCV) is a major global disease burden, often leading to chronic liver diseases, cirrhosis, cancer, and death in those infected. Despite the recent approval of antiviral therapeutics, a preventative vaccine is recognized as the most effective means to control HCV globally, particularly in at-risk and developing country populations. Here we describe the efforts and challenges related to the development of an HCV vaccine, which after decades of research have not been successful. Viral sequence variability poses a major challenge, yet recent research has provided unprecedented views of the atomic structure of HCV epitopes and immune recognition by antibodies and T cell receptors. This, coupled with insights from deep sequencing, robust neutralization assays, and other technological advances, is spurring research toward rationally HCV designed vaccines that preferentially elicit responses toward conserved epitopes of interest that are associated with viral neutralization and clearance. PMID- 27657662 TI - The experience of family caregivers caring for a terminal patient at home: A research review. AB - INTRODUCTION: One of the key aspects of the care of terminal patients is care delivered in their own home. Increasingly, the process of dying is moving from hospitals to homes. Although this process is directly related to the support of the social health environment, the involvement of family caregivers is essential. Given the impact that caring for a terminally ill family member has on people's lives, it is necessary to comprehend their personal experience in a holistic way. OBJECTIVE: To reveal the experience of family caregivers who are caring for a terminal patient in their home. DESIGN: A qualitative systematic review of articles published from 2000 to 2015 was conducted between March and September of 2015. The following databases were consulted: CINAHL, PubMed, PsycINFO, Cochrane Library, SciELO and Dialnet. After applying the selection criteria, 12 relevant studies were identified. Subsequently, two of the reviewers jointly performed a qualitative content analysis of them. RESULTS: The analysis permitted the caregivers' experiences to be grouped into five themes: 1) Learning the diagnosis: uncertainty about the future and the prospects of death; 2) Feeling the physical and emotional burden of care; 3) Experiencing a limited life; 4) Redefining the relationship with the person being cared for; and 5) Valuing the importance of the support of the environment. CONCLUSIONS: This review shows that caring for a family member with advanced illness in the home has a great impact on the personal realm of the caregiver and in the relationship he or she maintains with the ill family member. Being involved in the process of dying translates into a prodigious physical and psychological effort, together with a substantial limitation on the normal development of their own life. Additionally, the caregiver must face and establish a new relationship with the family member, in accordance with the new ethos, without the help of a formal structure providing the necessary support. These results may help to focus attention on family caregiver needs and to develop the knowledge necessary to meet the current demands of end-of-life health care in the home. PMID- 27657663 TI - Structured scoring of supporting nursing tasks to enhance early discharge in geriatric rehabilitation: The BACK-HOME quasi-experimental study. AB - INTRODUCTION: In geriatric rehabilitation it is important to have timely discharge of patients, especially if they have low nursing support needs. However, no instruments are available to identify early discharge potential. OBJECTIVE: To evaluate if weekly scoring of a nursing support scorecard in the evenings/nights and discussing the results in the multidisciplinary team meeting, leads to potential differences in discharge of geriatric rehabilitation patients. DESIGN: Quasi-experimental study with a reference cohort (n=200) and a Back-Home implementation cohort (n=283). SETTING/PARTICIPANTS: Patients in geriatric rehabilitation in the four participating skilled nursing facilities in the Netherlands. METHODS: Implementation of the nursing support scorecard during one year consisted of (1) weekly scoring of the scorecard to identify the supporting nursing tasks during the evenings/nights by trained nurses, and (2) discussion of the results in a multidisciplinary team meeting to establish if discharge home planning was feasible. Data on patients' characteristics and setting before admission were collected at admission; at discharge, the length of stay, discharge destination and barriers for discharge were collected by the nursing staff. RESULTS: Both cohorts were comparable with regard to median age, gender [reference cohort: 81 (IQR 75-88) years; 66% females vs. Back-Home cohort 82 (IQR 76-87) years; 71% females] and reasons for admission: stroke (23% vs. 23%), joint replacement (12% vs. 13%), traumatic injuries (31% vs. 34%), and other (35% vs. 30%). Overall, the median length of stay for the participants discharged home in the reference cohort was 56 (IQR 29-81) days compared to 46 (IQR 30-96) days in the Back-Home cohort (p=0.08). When no home adjustments were needed, participants were discharged home after 50 (IQR 29.5-97) days in the reference cohort, and after 42.5 (IQR 26-64.8) days in the Back-Home cohort (p=0.03). Reasons for discharge delay were environmental factors (36.7%) and patient-related factors, such as mental (21.5%) and physical capacity (33.9%). CONCLUSION: Structured scoring of supporting nursing tasks for geriatric rehabilitation patients may lead to earlier discharge from a skilled nursing facility to home, if no home adjustments are needed. PMID- 27657664 TI - Effects of smoking status and MADRS retardation factor on response to low frequency repetitive transcranial magnetic stimulation for depression. AB - BACKGROUND: Despite growing evidence supporting the clinical interest of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD), little is known regarding the effects of clinical and sociodemographic factors on the clinical outcome in patients. METHODS: We retrospectively investigated the effects of clinical (using the 3-factor model of the Montgomery-Asberg depression rating scale [MADRS] encompassing dysphoria, retardation and vegetative symptoms) and sociodemographic characteristics of participants on clinical outcome in a sample of 54 TRD patients receiving low frequency rTMS (1Hz, 360 pulses) applied over the right dorsolateral prefrontal cortex combined with sham venlafaxine. RESULTS: Responders (n=29) displayed lower retardation baseline scores (13.6+/-2.9) than non-responders (15.6+/-2.9; n=25; P=0.02). We also observed a significant difference between the numbers of ex smokers in responders and non-responders groups; all ex-smokers (n=8) were responders to rTMS (P=0.005). CONCLUSION: Low MADRS retardation factor and ex smoker status is highly prevalent in responders to low frequency rTMS. Further studies are needed to investigate the predictive value of these factors. PMID- 27657665 TI - Early-adult outcome of child and adolescent mental disorders as evidenced by a national-based case register survey. AB - BACKGROUND: Mental disorders show varying degrees of continuity from childhood to adulthood. This study addresses the relationship of child and adolescent mental disorders to early adult psychiatric morbidity. METHODS: From a population at risk of 830,819 children and adolescents aged 6-16 years, we selected all those (n=6043) who were enrolled for the first time in the Danish Psychiatric Register with an ICD-10 F00-99 diagnosis in 1995-1997, and identified any mental disorder for which they received treatment up to 2009. RESULTS: Neurodevelopmental and conduct disorders were the principal diagnostic groups at 6-16 years and exhibited a characteristic male preponderance; while affective, eating, neurotic, stress-related and adjustment disorders were more common in girls. Over a mean follow-up period of 10.1 years, 1666 (27.6%) cases, mean age 23.4 years, were referred for treatment to mental health services, and they had a markedly higher risk than the general population (RR 5.1; 95% CI 4.9-5.4). Affective, eating, neurodevelopmental, obsessive-compulsive and psychotic disorders had the strongest continuity. Heterotypic transitions were observed for affective, eating, neurodevelopmental, personality and substance use disorders. CONCLUSIONS: These findings suggest that individuals with psychiatric antecedents in childhood and adolescence had a high risk of being referred for treatment in early adulthood, and many mental disorders for which they required treatment revealed both homotypic and heterotypic continuity. PMID- 27657666 TI - Hierarchical group testing for multiple infections. AB - Group testing, where individuals are tested initially in pools, is widely used to screen a large number of individuals for rare diseases. Triggered by the recent development of assays that detect multiple infections at once, screening programs now involve testing individuals in pools for multiple infections simultaneously. Tebbs, McMahan, and Bilder (2013, Biometrics) recently evaluated the performance of a two-stage hierarchical algorithm used to screen for chlamydia and gonorrhea as part of the Infertility Prevention Project in the United States. In this article, we generalize this work to accommodate a larger number of stages. To derive the operating characteristics of higher-stage hierarchical algorithms with more than one infection, we view the pool decoding process as a time inhomogeneous, finite-state Markov chain. Taking this conceptualization enables us to derive closed-form expressions for the expected number of tests and classification accuracy rates in terms of transition probability matrices. When applied to chlamydia and gonorrhea testing data from four states (Region X of the United States Department of Health and Human Services), higher-stage hierarchical algorithms provide, on average, an estimated 11% reduction in the number of tests when compared to two-stage algorithms. For applications with rarer infections, we show theoretically that this percentage reduction can be much larger. PMID- 27657667 TI - Rebuttal from Dr. Mino-Kenudson. PMID- 27657668 TI - Mental Tasking and Caloric-Induced Vestibular Nystagmus Utilizing Videonystagmography. AB - PURPOSE: The purpose of this study was to quantify the effects of mental tasking on measures of the caloric vestibulo-ocular reflex utilizing videonystagmography as the measurement technique. METHOD: A within-subjects repeated-measures design was utilized. Sixteen healthy adults were evaluated (13 women, 3 men; ages 19-31 years). Each participant underwent bithermal caloric irrigation at 2 separate counterbalanced visits. At 1 visit mental tasking was utilized, whereas the other visit did not utilize mental tasking. The following outcomes were measured for each visit: peak slow-phase velocity (SPV), response duration, peak SPV latency, and eye blink artifact. RESULTS: No significant difference was seen for tasking versus no tasking with peak SPV, peak latency, or response duration. A significant difference was seen for the amount of eye blink artifact, with significantly more eye blinks present for the tasking condition. CONCLUSIONS: Results could indicate mental tasking does not affect the important measure of SPV. Moreover, increased eye blink artifact with tasking could obscure the clinician's ability to read the nystagmograph. However, this investigation is limited to the healthy young adult population, and more studies should be performed to corroborate the presented evidence. PMID- 27657669 TI - Solvatochromic Coatings with Self-Cleaning Property from Palygorskite@Polysiloxane/Crystal Violet Lactone. AB - Organic allochroic materials have wide potential applications in various fields but have so far been limited because of their low stability and low and slow switching reversibility. Because of the extraordinarily high durability of Maya Blue and the superhydrophobic lotus leaves, the new solvatochromic and self cleaning coatings with intense blue color are fabricated by the combination of polysiloxane-modified palygorskite (PAL@POS) and crystal violet lactone (CVL) via solid-state grinding. The coatings are characterized using scanning electron microscopy, diffusive reflection UV-vis spectra, and other analytical techniques. The hydrogen bonding of the hydroxyl groups of PAL@POS with the carboxylate groups of CVL+ is the origin of the intense blue color. The interruption of the hydrogen bonding by the vapor of solvents results in rapid discoloration of the coating. On the other hand, the evaporation of the solvents from the coating results in complete recovery of the original color by restoring the hydrogen bonding between PAL@POS and CVL+. The polarity, hydrogen bonding ability, and volatility of the solvents determine the solvatochromic properties of the coating. The PAL@POS/CVL coatings feature high reversibility and rapid switching between the colored and colorless states induced by the vapor of various solvents. Also, the coatings are superhydrophobic with fine self-cleaning properties and high durability in different environments. Moreover, the CVL content in the coating is controllable and can be as high as 4.8 wt %. PMID- 27657670 TI - Spatiotemporal Imaging of the Acoustic Field Emitted by a Single Copper Nanowire. AB - The monochromatic and geometrically anisotropic acoustic field generated by 400 and 120 nm diameter copper nanowires simply dropped on a 10 MUm silicon membrane is investigated in transmission using three-dimensional time-resolved femtosecond pump-probe experiments. Two pump-probe time-resolved experiments are carried out at the same time on both sides of the silicon substrate. In reflection, the first radial breathing mode of the nanowire is excited and detected. In transmission, the longitudinal and shear waves are observed. The longitudinal signal is followed by a monochromatic component associated with the relaxation of the nanowire's first radial breathing mode. Finite difference time domain (FDTD) simulations are performed and accurately reproduce the diffracted field. A shape anisotropy resulting from the large aspect ratio of the nanowire is detected in the acoustic field. The orientation of the underlying nanowires is thus acoustically deduced. PMID- 27657671 TI - Update: Influenza Activity - United States and Worldwide, May 22-September 10, 2016. AB - During May 22-September 10, 2016,* the United States experienced typical low levels of seasonal influenza activity overall; beginning in late August, clinical laboratories reported a slight increase in influenza positive test results and CDC received reports of a small number of localized influenza outbreaks caused by influenza A (H3N2) viruses. Influenza A (H1N1)pdm09, influenza A (H3N2), and influenza B viruses were detected during May-September in the United States and worldwide. The majority of the influenza viruses collected from the United States and other countries during that time have been characterized antigenically or genetically or both as being similar to the reference viruses representing vaccine components recommended for the 2016-17 Northern Hemisphere vaccine. During May 22-September 10, 2016, 20 influenza variant virus? infections were reported; two were influenza A (H1N2) variant (H1N2v) viruses (Minnesota and Wisconsin) and 18 were influenza A (H3N2) variant (H3N2v) viruses (12 from Michigan and six from Ohio). PMID- 27657672 TI - Diagnostic Microdosing Approach to Study Gemcitabine Resistance. AB - Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. We determined whether subtherapeutic "microdoses" of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of 14C-labeled gemcitabine for 4-24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. These results support gemcitabine levels in DNA as a potential biomarker of drug cytotoxicity. PMID- 27657674 TI - Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score. AB - Importance: REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline alpha-fetoprotein (alphaFP). Objective: To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial. Design, Settings, and Participants: Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis; 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child Pugh scores 7 and 8). Interventions: Ramucirumab (8 mg/kg) or placebo intravenously plus best supportive care every 2 weeks. Main Outcomes and Measures: Overall survival (OS), defined as time from randomization to death from any cause. Results: In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P = .06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline alphaFP levels of 400 ng/mL (to convert ng/mL to MUg/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61; 95% CI, 0.43-0.87; P = .01) and Child-Pugh 6 (HR, 0.64; 95% CI, 0.42-0.98; P = .04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher incidence of grade 3 or higher treatment-emergent adverse events, including ascites and asthenia, and special-interest events, including liver injury and/or failure and bleeding, compared with patients with Child-Pugh scores of 5 or 6. Conclusions and Relevance: In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline alphaFP levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A cirrhosis and baseline alphaFP levels of 400 ng/mL or more. Trial Registration: clinicaltrials.gov Identifier: NCT01140347. PMID- 27657675 TI - [Survey of Training in Laparoscopic Skills in Germany]. AB - Background: Training in laparoscopic skills on simulators such as box-, POP- or VR-trainers improves intraoperative performance. Although this training is not mandatory in Germany at the moment, certified centres for minimally invasive surgery need to account for training opportunities. According to previous surveys, laparoscopic simulators are desired, yet not sufficiently available. The aim of the current project was a structured analysis of laparoscopic simulation sites in Germany. Materials and Methods: An online survey was performed among members of the "Deutsche Gesellschaft fur Allgemein- und Viszeralchirurgie". This consisted of 16 questions on the availability, type, use and financing of a laparoscopic simulator. If more than one person in an institution completed the questionnaire, answers were pooled and an analysis of clinics as well as single persons was performed. Results: Of 4605 persons, 422 participants (9.2 %) from 265 different departments completed the survey. In 140 Institutions (52.8 %) a simulator for laparoscopic training was present. No training possibility was available in 37.8 % (n = 99) of the hospitals. A curriculum for laparoscopic training was obtained in 43.3 % (n = 103) of the participants with laparoscopic training facilities. The use of available simulators by surgical residents increased when they were embedded in a mandatory training curriculum (at least monthly use: 33.3 vs. 57.1 %). Conclusion: Compared to previous surveys, the proportion of hospitals with simulators is increasing. Their use is currently very heterogenous. A mandatory basic curriculum may encourage acquisition of more simulators. A DGAV database is supposed to encourage cooperation between training centres and clinics without simulators. PMID- 27657673 TI - Analysis of Discrepancy Between Diagnostic Clinical Examination Findings and Corresponding Evaluation of Digital Images in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study. AB - Importance: As effective treatments for potentially blinding retinopathy of prematurity (ROP) have been introduced, the importance of consistency in findings has increased, especially with the shift toward retinal imaging in infants at risk of ROP. Objective: To characterize discrepancies in findings of ROP between digital retinal image grading and examination results from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity study, conducted from May 2011 to October 2013. Design, Setting, and Participants: A poststudy consensus review of images was conducted by 4 experts, who examined discrepancies in findings between image grades by trained nonphysician readers and physician examination results in infants with referral-warranted ROP (RW-ROP). Images were obtained from 13 North American neonatal intensive care units from eyes of infants with birth weights less than 1251 g. For discrepancy categories with more than 100 cases, 40 were randomly selected; in total, 188 image sets were reviewed. Main Outcomes and Measures: Consensus evaluation of discrepant image and examination findings for RW-ROP components. Results: Among 5350 image set pairs, there were 161 instances in which image grading did not detect RW-ROP noted on clinical examination (G-/E+) and 854 instances in which grading noted RW ROP when the examination did not (G+/E-). Among the sample of G-/E+ cases, 18 of 32 reviews (56.3%) agreed with clinical examination findings that ROP was present in zone I and 18 of 40 (45.0%) agreed stage 3 ROP was present, but only 1 of 20 (5.0%) agreed plus disease was present. Among the sample of G+/E- cases, 36 of 40 reviews (90.0%) agreed with readers that zone I ROP was present, 23 of 40 (57.5%) agreed with readers that stage 3 ROP was present, and 4 of 16 (25.0%) agreed that plus disease was present. Based on the consensus review results of the sampled cases, we estimated that review would agree with clinical examination findings in 46.5% of the 161 G-/E+ cases (95% CI, 41.6-51.6) and agree with trained reader grading in 70.0% of the 854 G+/E- cases (95% CI, 67.3-72.8) for the presence of RW-ROP. Conclusions and Relevance: This report highlights limitations and strengths of both the remote evaluation of fundus images and bedside clinical examination of infants at risk for ROP. These findings highlight the need for standardized approaches as ROP telemedicine becomes more widespread. PMID- 27657676 TI - Mastering genomic terminology. PMID- 27657677 TI - Ethical considerations for genetic testing in the context of mandated cardiac screening before athletic participation. PMID- 27657678 TI - All your data (effectively) belong to us: data practices among direct-to-consumer genetic testing firms. AB - PURPOSE: Direct-to-consumer genetic testing (DTC-GT) has become a convenient method to help people to understand their genetic makeup. Owing in part to concerns regarding confidentiality, privacy, and secondary use of data, professional and government bodies created guidelines to promote transparency among these companies. Using a comprehensive and systematic approach, this study assessed DTC-GT company compliance with international transparency guidelines. METHODS: A framework analysis was performed on 30 DTC-GT health and/or ancestry websites identified using a US-based online search strategy during the summer of 2015. A codebook was developed from a synthesis of relevant guidelines from seven DTC-GT guideline documents and applied to each website. RESULTS: Although most companies met guidelines related to transparency regarding security protocols, storage procedures, and third-party disclosures, few met guidelines regarding sharing risks from data disclosures. Additionally, few companies disclosed how long data would be kept for services or research. Use of data for research was frequently mentioned only in privacy policies and terms of service documents, and only two-thirds of companies required an additional consent to use consumer data for health-related research. CONCLUSION: Our analysis shows that DTC-GT companies do not consistently meet international transparency guidelines related to confidentiality, privacy, and secondary use of data.Genet Med advance online publication 22 September 2016. PMID- 27657679 TI - Response to van Rijt et al. PMID- 27657680 TI - A dominant variant in DMXL2 is linked to nonsyndromic hearing loss. AB - PURPOSE: To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss. METHODS: Genome-wide linkage analysis was performed for 21 family members. Candidate pathogenic variants were identified by whole-exome sequencing of selected family members and confirmed by Sanger sequencing of all family members. Cochlear expression of Dmxl2 was investigated by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining of the organ of Corti from mice. RESULTS: The causative gene was mapped to a 9.68-Mb candidate region on chromosome 15q21.2 (maximum logarithm of the odds score = 4.03) that contained no previously described deafness genes. Whole-exome sequencing identified heterozygous c.7250G>A (p.Arg2417His) in DMXL2 as the only candidate pathogenic variant segregating the hearing loss. In mouse cochlea, expression of DMXL2 was restricted to the hair cells and the spiral ganglion neurons. CONCLUSION: Our data indicated that the p.Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.Genet Med advance online publication 22 September 2016. PMID- 27657682 TI - Payer decision making for next-generation sequencing-based genetic tests: insights from cell-free DNA prenatal screening. AB - PURPOSE: Cell-free DNA (cfDNA) prenatal screening tests have been rapidly adopted into clinical practice, due in part to positive insurance coverage. We evaluated the framework payers used in making coverage decisions to describe a process that should be informative for other sequencing tests. METHODS: We analyzed coverage policies from the 19 largest US private payers with publicly available policies through February 2016, building from the University of California San Francisco TRANSPERS Payer Coverage Policy Registry. RESULTS: All payers studied cover cfDNA screening for detection of trisomies 21, 18, and 13 in high-risk, singleton pregnancies, based on robust clinical validity (CV) studies and modeled evidence of clinical utility (CU). Payers typically evaluated the evidence for each chromosomal abnormality separately, although results are offered as part of a panel. Starting in August 2015, 8 of the 19 payers also began covering cfDNA screening in average-risk pregnancies, citing recent CV studies and updated professional guidelines. Most payers attempted, but were unable, to independently assess analytic validity (AV). CONCLUSION: Payers utilized the standard evidentiary framework (AV/CV/CU) when evaluating cfDNA screening but varied in their interpretation of the sufficiency of the evidence. Professional guidelines, large CV studies, and decision analytic models regarding health outcomes appeared highly influential in coverage decisions.Genet Med advance online publication 22 September 2016. PMID- 27657684 TI - Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. AB - PURPOSE: We began screening newborns for biotinidase deficiency disorder in 1984, and now all states in the United States and many countries perform this screening. The purpose of this study was to determine the outcomes of older adolescent and adult individuals with the disorder identified by newborn screening. SUBJECTS AND METHODS: We located and surveyed, by questionnaire and telephone interviews, 44 individuals with profound biotinidase deficiency identified by newborn screening with a mean age of 23.1 years. RESULTS: All individuals had successfully completed high school, and many were attending or had completed college or graduate school. Compliance in using biotin has been excellent. Several individuals developed a variety of symptoms when they discontinued biotin for days or weeks. These features readily resolved when biotin was resumed. In addition, five treated women had nine uneventful pregnancies and deliveries. CONCLUSIONS: Newborn screening for profound biotinidase deficiency and early treatment with biotin result in excellent outcomes for older adolescents and adults with the disorder. In addition, mothers with profound biotinidase deficiency who were treated with biotin had pregnancies with good outcomes. These outcome results indicate that newborn screening for biotinidase deficiency is one of the most successful newborn screening programs.Genet Med 19 4, 396-402. PMID- 27657681 TI - The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. AB - PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the alpha-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of alpha-galactosidase A to restore lysosomal activity. METHODS: A pharmacogenetic assay was used to identify the alpha-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in alpha-galactosidase A activity were measured by a good laboratory practice (GLP) validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies. RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell alpha-galactosidase A responses to migalastat in male patients showed high sensitivity, specificity, and positive and negative predictive values (>=0.875). GLP HEK assay results were also predictive of decreases in kidney globotriaosylceramide in males and plasma globotriaosylsphingosine in males and females. The clinical study subset of amenable mutations (n = 51) was representative of all 268 amenable mutations identified by the GLP HEK assay. CONCLUSION: The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat.Genet Med 19 4, 430-438. PMID- 27657683 TI - Prescription medication changes following direct-to-consumer personal genomic testing: findings from the Impact of Personal Genomics (PGen) Study. AB - PURPOSE: To measure the frequency of prescription medication changes following direct-to-consumer personal genomic testing (DTC-PGT) and their association with the pharmacogenomic results received. METHODS: New DTC-PGT customers were enrolled in 2012 and completed surveys prior to the return of results and 6 months after results; DTC-PGT results were linked to survey data. "Atypical response" pharmacogenomic results were defined as those indicating an increase or decrease in risk of an adverse drug event or likelihood of therapeutic benefit. At follow-up, participants reported prescription medication changes and health care provider consultation. RESULTS: Follow-up data were available from 961 participants, of whom 54 (5.6%) reported changing a medication they were taking or starting a new medication due to their DTC-PGT results. Of these, 45 (83.3%) reported consulting with a health-care provider regarding the change. Pharmacogenomic results were available for 961 participants, of which 875 (91.2%) received one or more atypical response results. For each such result received, the odds of reporting a prescription medication change increased 1.57 times (95% confidence interval = 1.17, 2.11). CONCLUSION: Receipt of pharmacogenomic results indicating an atypical drug response is common with DTC-PGT and is associated with prescription medication changes; however, fewer than 1% of consumers report unsupervised changes at 6 months after testing.Genet Med advance online publication 22 September 2016. PMID- 27657685 TI - Multidisciplinary model to implement pharmacogenomics at the point of care. AB - PURPOSE: Despite potential clinical benefits, implementation of pharmacogenomics (PGx) faces many technical and clinical challenges. These challenges can be overcome with a comprehensive and systematic implementation model. METHODS: The development and implementation of PGx were organized into eight interdependent components addressing resources, governance, clinical practice, education, testing, knowledge translation, clinical decision support (CDS), and maintenance. Several aspects of implementation were assessed, including adherence to the model, production of PGx-CDS interventions, and access to educational resources. RESULTS: Between August 2012 and June 2015, 21 specific drug-gene interactions were reviewed and 18 of them were implemented in the electronic medical record as PGx-CDS interventions. There was complete adherence to the model with variable production time (98-392 days) and delay time (0-148 days). The implementation impacted approximately 1,247 unique providers and 3,788 unique patients. A total of 11 educational resources complementary to the drug-gene interactions and 5 modules specific for pharmacists were developed and implemented. CONCLUSION: A comprehensive operational model can support PGx implementation in routine prescribing. Institutions can use this model as a roadmap to support similar efforts. However, we also identified challenges that will require major multidisciplinary and multi-institutional efforts to make PGx a universal reality.Genet Med 19 4, 421-429. PMID- 27657686 TI - The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort. AB - PURPOSE: It has been argued that rare diseases should be recognized as a public health priority. However, there is a shortage of epidemiological data describing the true burden of rare diseases. This study investigated hospital service use to provide a better understanding of the collective health and economic impacts of rare diseases. METHODS: Novel methodology was developed using a carefully constructed set of diagnostic codes, a selection of rare disease cohorts from hospital administrative data, and advanced data-linkage technologies. Outcomes included health-service use and hospital admission costs. RESULTS: In 2010, cohort members who were alive represented approximately 2.0% of the Western Australian population. The cohort accounted for 4.6% of people discharged from hospital and 9.9% of hospital discharges, and it had a greater average length of stay than the general population. The total cost of hospital discharges for the cohort represented 10.5% of 2010 state inpatient hospital costs. CONCLUSIONS: This population-based cohort study provides strong new evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs. The methodology will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases.Genet Med advance online publication 22 September 2016. PMID- 27657688 TI - Using large sequencing data sets to refine intragenic disease regions and prioritize clinical variant interpretation. AB - PURPOSE: Classification of novel variants is a major challenge facing the widespread adoption of comprehensive clinical genomic sequencing and the field of personalized medicine in general. This is largely because most novel variants do not have functional, genetic, or population data to support their clinical classification. METHODS: To improve variant interpretation, we leveraged the Exome Aggregation Consortium (ExAC) data set (N = ~60,000) as well as 7,000 clinically curated variants in 132 genes identified in more than 11,000 probands clinically tested for cardiomyopathies, rasopathies, hearing loss, or connective tissue disorders to perform a systematic evaluation of domain level disease associations. RESULTS: We statistically identify regions that are most sensitive to functional variation in the general population and also most commonly impacted in symptomatic individuals. Our data show that a significant number of exons and domains in genes strongly associated with disease can be defined as disease sensitive or disease-tolerant, leading to potential reclassification of at least 26% (450 out of 1,742) of variants of uncertain clinical significance in the 132 genes. CONCLUSION: This approach leverages domain functional annotation and associated disease in each gene to prioritize candidate disease variants, increasing the sensitivity and specificity of novel variant assessment within these genes.Genet Med advance online publication 22 September 2016. PMID- 27657689 TI - Neonates at risk of medium-chain acyl-CoA dehydrogenase deficiency: a perinatal protocol for use before population neonatal screening test results become available. PMID- 27657687 TI - Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. AB - PURPOSE: To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis for patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). METHODS: WES was performed in 62 families with CAKUT. WES data were analyzed for single-nucleotide variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). RESULTS: In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these eight individuals with FOXP1 SNVs have syndromic urinary tract defects, implicating this gene in urinary tract development. CONCLUSION: We conclude that WES can be used to identify molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.Genet Med 19 4, 412-420. PMID- 27657690 TI - Prognostic Values of Vimentin Expression and Its Clinicopathological Significance in Non-Small Cell Lung Cancer: A Meta-Analysis of Observational Studies with 4118 Cases. AB - BACKGROUND: Vimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC. METHODS: Databases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) 'vimentin' OR 'vim' OR 'vmt' OR 'vm' OR 'hel113' OR 'ctrct30' and (2) 'pulmon*' OR 'lung' OR 'alveolar' and (3) 'cancer' OR 'carcinoma' OR 'tumor' OR 'adenocarcinoma' OR 'squamous' OR 'neoplas*' OR 'malignan*'. The data were combined by random effect model and the H value and I2 were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0. RESULTS: Thirty-two qualified studies (4118 cases) were included in the current meta analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315-2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906-1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921-1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985-1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098-1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664-2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987-5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063 11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857-3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052-2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397-3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05). CONCLUSION: An overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC. PMID- 27657692 TI - Right care, right place, right time: improving the timeliness of health care in New South Wales through a public-private hospital partnership. AB - Objective The overall aim of the study was to investigate and assess the feasibility of improving the timeliness of public hospital care through a New South Wales (NSW)-wide public-private hospital partnership. Methods The study reviewed the academic and professional grey literature, and undertook exploratory analyses of secondary data acquired from two national health data repositories informing in-patient access and utilisation across NSW public and private hospitals. Results In 2014-15, the NSW public hospital system was unable to deliver care within the medically recommended time frame for over 27400 people who were awaiting elective surgery. Available information indicates that the annual commissioning of 15% of public in-patient rehabilitation bed days to the private hospital system would potentially free up enough capacity in the NSW public hospital system to enable elective surgery for all public patients within recommended time frames. Conclusions The findings of the study justify a strategic whole-of-health system approach to reducing public patient wait times in NSW and highlight the need for research efforts aimed at securing a better understanding of available hospital capacity across the public and private hospital systems, and identifying and testing workable models that improve the timeliness of public hospital care. What is known about the topic? There are very few studies available to inform public-private hospital service partnerships and the opportunities available to improve timely health care access through such partnerships. What does this paper add? This paper has the potential to open and prompt timely discussion and debate, and generate further fundamental investigation, on public-private hospital service partnerships in Australia where opportunity is available to address elective surgery wait times in a reliable and effective manner. What are the implications for practitioners? The NSW Ministry of Health and its Local Health Districts have the potential to realise a key objective, namely to deliver the 'right care, in the right place, at the right time', through the core value of collaboration, using available infrastructure. PMID- 27657691 TI - A Global Analysis of the Polygalacturonase Gene Family in Soybean (Glycine max). AB - Polygalacturonase is one of the pectin hydrolytic enzymes involved in various developmental and physiological processes such as seed germination, organ abscission, pod and anther dehiscence, and xylem cell formation. To date, no systematic analysis of polygalacturonase incorporating genome organization, gene structure, and expression profiling has been conducted in soybean (Glycine max var. Williams 82). In this study, we identified 112 GmPG genes from the soybean Wm82.a2v1 genome. These genes were classified into three groups, group I (105 genes), group II (5 genes), and group III (2 genes). Fifty-four pairs of duplicate paralogous genes were preferentially identified from duplicated regions of the soybean genome, which implied that long segmental duplications significantly contributed to the expansion of the GmPG gene family. Moreover, GmPG transcripts were analyzed in various tissues using RNA-seq data. The results showed the differential expression of 64 GmPGs in the tissue and partially redundant expression of some duplicate genes, while others showed functional diversity. These findings suggested that the GmPGs were retained by substantial subfunctionalization during the soybean evolutionary processes. Finally, evolutionary analysis based on single nucleotide polymorphisms (SNPs) in wild and cultivated soybeans revealed that 107 GmPGs had selected site(s), which indicated that these genes may have undergone strong selection during soybean domestication. Among them, one non-synonymous SNP of GmPG031 affected floral development during selection, which was consistent with the results of RNA-seq and evolutionary analyses. Thus, our results contribute to the functional characterization of GmPG genes in soybean. PMID- 27657693 TI - Prevalent and Incident Vertebral Deformities in Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN). AB - BACKGROUND: Vertebral fractures are the most common type of osteoporotic fracture among women, but estimates of their prevalence and incidence during middle-age are limited. The development of vertebral morphometry (VM) using dual energy X ray absorptiometry (DXA) makes it more feasible to measure VM in large, longitudinal, observational studies. We conducted this study to: 1) contribute to the scant knowledge of the prevalence, incidence and risk factors for vertebral deformities in middle-aged women; and 2) to evaluate the performance of DXA-based VM measurement in a large, community based sample. METHODS: The sample is derived from the Study of Women's Health Across the Nation (SWAN), a multi-site, community-based, longitudinal cohort study of the MT. Using Hologic QDR 4500A instruments, we acquired initial VM measurements in 1446 women during calendar years 2004-2007; in 2012-2013, a follow-up VM was obtained in 1108. Annually, lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) were measured and participant characteristics were assessed with standardized instruments. Multivariable logistic regression models examined the relations between prevalent deformity and relevant characteristics. Analyses of characteristics associated with prevalent deformity were restricted to 824 women who had not taken bone active medications since SWAN baseline. We calculated incident deformity per person year (PY) of observation, standardized to 1000 person-years. RESULTS: The cranial portion of the VM image yielded the lowest proportions of readable vertebrae: from T4 through T6, between 43% and 63% of vertebral bodies were evaluable. Greater BMI was associated with fewer readable levels (B = -0.088, p<0.0001). In the baseline sample of 1446 women, the prevalence of vertebral deformity was 3.2% (95% CI: 2.3, 4.1). The relative odds of deformity increased by 61% per SD decrement in baseline LS BMD (p = 0.02) and were 67% greater per SD decrement in baseline FN BMD (p = 0.04). Odds of prevalent deformity increased by 21% per year increment in age (p = 0.02). On average, 1108 women were followed for 6.8 years (SD 0.5 years, range 5.1-8.3 years) and we observed an incidence of 1.98 vertebral deformities per 1000 PY. In the longitudinal sample, 628 participants had never used bone active medications; their vertebral deformity incidence was 2.8 per 1000 PY. CONCLUSION: Prevalence of vertebral deformity in SWAN participants aged 50-60 years was low and lower bone density at the LS and FN was strongly related to greater risk of prevalent deformity. Only about half of the vertebral levels between T4-T6 could be adequately imaged by DXA. Greater BMI is associated with fewer readable vertebral levels. PMID- 27657694 TI - Novel Strategy for Phenotypic Characterization of Human B Lymphocytes from Precursors to Effector Cells by Flow Cytometry. AB - A precise identification and phenotypic characterization of human B-cell subsets is of crucial importance in both basic research and medicine. In the literature, flow cytometry studies for the phenotypic characterization of B-lymphocytes are mainly focused on the description of a particular cell stage, or of specific cell stages observed in a single type of sample. In the present work, we propose a backbone of 6 antibodies (CD38, CD27, CD10, CD19, CD5 and CD45) and an efficient gating strategy to identify, in a single analysis tube, a large number of B-cell subsets covering the whole B-cell differentiation from precursors to memory and plasma cells. Furthermore, by adding two antibodies in an 8-color combination, our approach allows the analysis of the modulation of any cell surface marker of interest along B-cell differentiation. We thus developed a panel of seven 8 colour antibody combinations to phenotypically characterize B-cell subpopulations in bone marrow, peripheral blood, lymph node and cord blood samples. Beyond qualitative information provided by biparametric representations, we also quantified antigen expression on each of the identified B-cell subsets and we proposed a series of informative curves showing the modulation of seventeen cell surface markers along B-cell differentiation. Our approach by flow cytometry provides an efficient tool to obtain quantitative data on B-cell surface markers expression with a relative easy-to-handle technique that can be applied in routine explorations. PMID- 27657696 TI - Energetics, Thermodynamics, and Hydrogen Bonding Diversity in Ammonium Halide Clusters. AB - Contributions from different intermolecular and interionic forces, as well as variations in bond energies, produce size-dependent variations in the structures of acid-base molecular clusters. In this work the structures and interaction energetics of cluster particles with the nominal formulas (NH4X)n, X = (F, Cl, Br) are predicted using either "mag-walking" sawtooth simulated annealing Monte Carlo calculations or model building, followed by M06-2X or RI-MP2 geometry optimization and single-point energy calculations. Whereas the n = 1 clusters all exhibit a single hydrogen bond, small (NH4F)n particles (n = 2-5) exhibit three distinct types of hydrogen bonds as a function of size (traditional, ion-pair and proton-shared). However, (NH4Br)n and (NH4Cl)n particles (n = 2-13) all solely exhibit ion-pair hydrogen bonding, with even values of n exhibiting pronounced relative stability. The computed differential interaction energy of the bromide and chloride systems is generally near the bulk limit of the difference in their accepted lattice energies, despite the fact that their structures do not resemble the bulk crystal structures. Nanoparticle growth reactions are predicted to be thermodynamically spontaneous under standard conditions, with significant size and system dependencies. This work is designed to further our understanding of the nature of hydrogen bonding and other intermolecular forces, particularly within ionic nanocrystallites, as well as the thermodynamics of cluster formation. PMID- 27657695 TI - Using the Portuguese version of the Bicultural Scale in Brazil. AB - Introduction:: Brazil has received influxes of people, mainly from Africa, Europe and Japan, forming one of the most heterogeneous populations in the world. Some groups, particularly in Southern Brazil, have retained their original cultural traditions, whilst acquiring elements of the typical local Brazilian cultural identity. This is the first study designed to formally evaluate biculturality in Brazil. Objective:: To psychometrically assess and validate the Portuguese version of the Bicultural Scale (BS) in Brazil. Methods:: The BS was adapted and translated to Portuguese and tested for the first time in Brazil in a sample of descendants (n = 160) from four immigrant groups and respective locations in Southern Brazil. A series of psychometric tests were conducted in order to examine the validity of the Portuguese version of the BS. Analyses of variance across scores for all subgroups were also conducted. Results:: Factor analysis revealed two main factors contributing to most of the variance in scores. The 10 items measuring affiliation with minority cultural characteristics and the typical Brazilian culture yielded Cronbach's alpha coefficients of 0.69 and 0.78 respectively, whereas the overall Cronbach's alpha for all 20 items of the BS was 0.67. There was a significant correlation between items related to the typical Brazilian culture and the generation since immigration of research participants (r = 0.23, p = 0.004). The mean time taken to complete the questionnaire was 7.4 minutes. Conclusion:: The results indicate that the Portuguese version of the BS is a valid, reliable and easy-to-use instrument to assess biculturality experienced by descendants of immigrants in southern Brazil. PMID- 27657699 TI - Correction: Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1. AB - [This corrects the article DOI: 10.1371/journal.pone.0159826.]. PMID- 27657697 TI - COMT Val158Met Polymorphism Modulates Huntington's Disease Progression. AB - Little is known about the genetic factors modulating the progression of Huntington's disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington's Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression. PMID- 27657698 TI - Parabrachial complex links pain transmission to descending pain modulation. AB - The rostral ventromedial medulla (RVM) has a well-documented role in pain modulation and exerts antinociceptive and pronociceptive influences mediated by 2 distinct classes of neurons, OFF-cells and ON-cells. OFF-cells are defined by a sudden pause in firing in response to nociceptive inputs, whereas ON-cells are characterized by a "burst" of activity. Although these reflex-related changes in ON- and OFF-cell firing are critical to their pain-modulating function, the pathways mediating these responses have not been identified. The present experiments were designed to test the hypothesis that nociceptive input to the RVM is relayed through the parabrachial complex (PB). In electrophysiological studies, ON- and OFF-cells were recorded in the RVM of lightly anesthetized male rats before and after an infusion of lidocaine or muscimol into PB. The ON-cell burst and OFF-cell pause evoked by noxious heat or mechanical probing were substantially attenuated by inactivation of the lateral, but not medial, parabrachial area. Retrograde tracing studies showed that neurons projecting to the RVM were scattered throughout PB. Few of these neurons expressed calcitonin gene-related peptide, suggesting that the RVM projection from PB is distinct from that to the amygdala. These data show that a substantial component of "bottom-up" nociceptive drive to RVM pain-modulating neurons is relayed through the PB. While the PB is well known as an important relay for ascending nociceptive information, its functional connection with the RVM allows the spinoparabrachial pathway to access descending control systems as part of a recurrent circuit. PMID- 27657700 TI - Correlates of Sexually Transmitted Infections among Adolescents Attending Public High Schools, Panama, 2015. AB - BACKGROUND: Sexually transmitted infections (STIs) are common in adolescents worldwide. Vulnerability to STIs increases with risky sexual practices. This study described the sexual practices, estimated the prevalence of STIs, and identified correlates associated with STIs among participants, enrolled in public high schools, in the District of Panama, Panama. METHODS: A cross sectional study, using multistage cluster sampling, was conducted among participants, aged 14-18 years, enrolled in public high schools, in the District of Panama, Panama City, Panama, from August to November, 2015. Participants completed a self administered questionnaire and provided biological samples. The samples of those reporting sexual activity (oral, vaginal, and/or anal intercourse) were tested for STIs. Odds ratios were used to identify correlates of STIs in this population. RESULTS: A total of 592 participants were included, of whom, 60.8% reported a history of sexual activity, and 24.4% tested positive for least one STI. STIs were more common in female participants, (33.5%). Compared to those without STIs, higher proportions of those with at least one STI reported >=3 sexual partners in their lifetime (60.0%) and current sexual activity (76.3%). In the multivariable model, correlates of STI included female participants (Adjusted Odds Ratio (AOR) = 5.8, 95% Confidence Interval (CI) 2.3-14.6) and those who engaged in sexual intercourse with casual partners (AOR = 3.0, 95% CI: 1.2-7.5). CONCLUSIONS: We report a high STI prevalence among adolescents attending public high schools, in the District of Panama. Reported risky sexual practices were common and correlated with STIs. Female participants and those reporting sexual intercourse with casual partners were more likely test positive for at least one STI. Our study identified a need for effective interventions to curb future infections in this population. PMID- 27657702 TI - The Clock Is Ticking: Countdown to Metastases. PMID- 27657701 TI - Filling GAPs in our knowledge: ARHGAP11A and RACGAP1 act as oncogenes in basal like breast cancers. AB - Like RAS proteins, the aberrant function of RHO family small GTPases has been implicated in driving cancer development and growth. However, unlike the RAS family, where gain-of-function missense mutations are found in ~25% of all human cancers, missense mutations are relatively rare in RHO proteins. Instead, altered RHO activity in cancer more commonly arises through the aberrant functions of RHO GTPase regulators. In many cancer types, altered expression and/or mutation of RHO-selective guanine nucleotide exchange factors (RHOGEFs) or GTPase-activating proteins (RHOGAPs), which activate or inactivate RHO GTPases, respectively, is observed. For example, deletion or loss of expression of the RHOA GAP DLC1 is well-established to drive cancer growth. Recently, we identified high expression of 2 RHOGAPs, ARHGAP11A and RACGAP1, in the basal-like breast cancer subtype. Unexpectedly, both of these RHOA GAPs exhibited properties of oncoproteins rather than tumor suppressors, in contrast to DLC1. In this commentary, we summarize our findings and speculate that different RHOA GAPs can play distinct roles in cancer depending on their spatial regulation and cancer type context. We also evaluate our results in light of recently-described cancer genome sequencing studies that have identified loss-of-function mutations of RHOA in specific cancer types. PMID- 27657703 TI - Hematologic and Biochemical Biologic Variation in Laboratory Cats. AB - The biologic variation associated with a clinical pathology result is important to consider before reference intervals (RI) are used. Most available RI are population-based RI, in which the analytical variability, interindividual variability, and intraindividual variability are confounded. In addition, when the intraindividual variability is considerably less than the interindividual variability, a population-based RI is insufficiently sensitive to detect changes in a subject over time. Here we determined the biologic variation and reference change value (RCV) of hematologic and biochemical variables in laboratory cats. Blood specimens from 14 (7 females and 7 males) overnight-fasted laboratory cats sampled 7 times (days 1, 2, 7, 14, 31, 42, and 100) were analyzed regarding hematology and biochemistry variables. For each variable, analytical, intraindividual, and interindividual coefficients of variation were estimated prior to calculation of the index of individuality and the RCV. RBC variables (count, Hgb, Hct, MCV, MCH, MCHC, and RBC distribution width) and 5 biochemical analytes (cholesterol, creatinine, triglycerides, ALP, and calcium) exhibited marked individuality, therefore indicating that subject-based reference intervals or RCV would be preferable when monitoring these variables in laboratory cats. Population-based RI were shown to be adequate for glucose and sodium, and both types of population and individual RI were similarly efficient for albumin, total protein, urea, ALT, AST, creatine kinase, chloride, carbon dioxide, iron, magnesium, inorganic phosphate, and potassium and reticulocyte, WBC, neutrophil, lymphocyte, monocyte, eosinophil, and platelet counts. The RCV determined in the present study provide a valuable tool for monitoring hematologic and biochemical variables in healthy laboratory cats. PMID- 27657704 TI - Effects of Embryo Transfer on Emotional Behaviors in C57BL/6 Mice. AB - Microbiologic standardization plays a key role in the management of animal facilities because contamination of stock could affect the health status and wellbeing of animals and thereby induce artifacts in biomedical research. One common method to avoid the dissemination of pathogens is embryo transfer (ET). Although disturbances in the perinatal environment may cause long-lasting effects on the behavior and physiology of mouse offspring, the influences of ET during this sensitive phase have not yet been addressed. Our study investigated the effects of various components of ET (anesthesia, surgery, recipient strain) on the behavior of dams (exploration, nest-building) and offspring (nest-building, exploration, anxiety, and social and depressive-like behaviors). For ET, the donor strain C57BL/6N and a standard protocol were used. Whereas treatment with anesthesia-analgesia did not affect maternal behavior, female offspring demonstrated overall effects on weight gain and corticosterone levels. Compared with naturally delivered female offspring, dams obtained through ET demonstrated decreased exploration and nest-building. In addition, female ET-derived offspring had enhanced levels of anxiety and increased social interest. Furthermore, ET derived dams obtained by using NMRI as the recipient strain showed increased exploratory behavior compared with that of dams obtained by using C57 mice as recipients. Compared with using C57 as recipients, both sexes of offspring transferred into NMRI recipients weighed more, and female mice showed a depressive-like phenotype. Our findings suggest that ET, now considered to be a routine procedure in animal husbandry, bears the risk of introducing artifacts. PMID- 27657705 TI - Cryotolerance of Sperm from Transgenic Rhesus Macaques (Macaca mulatta). AB - Cryopreservation is an important tool routinely used in preserving sperm for assisted reproductive technologies and for genetic preservation of unique animal models. Here we investigated the viability of fresh and frozen sperm from rhesus macaques on the basis of motility, membrane integrity, and acrosome integrity. Sperm motility was determined by visual evaluation; membrane and acrosome integrity were assessed simultaneously through triple staining with Hoechst 33342, propidium iodide, and fluorescein isothiocyanate-peanut agglutinin. We compared thawed semen that had been cryopreserved by using 2 different media with fresh semen from wildtype (WT) macaques; fresh semen from a model of Huntington disease (HD) with fresh WT semen; and fresh HD with cryopreserved-thawed HD semen. Our new freezing media (TEST EQ) preserved the acrosome better, with less net damage, than did traditional TEST (egg yolk extender containing TES and Tris) media. In addition, the percentage of membrane-damaged cells was similar in fresh HD semen (38.6%+/-2.9%) and WT semen (35.5%+/-1.9%). Membrane and acrosomal damage were not different between HD and WT sperm after cryopreservation and subsequent thawing. Furthermore, cryopreservation had similar negative effects on the motility of HD and WT sperm. These data illustrate that semen from a rhesus macaque model of HD is similarly cryotoleratant to that from WT animals. PMID- 27657706 TI - Effect of Ventilated Caging on Water Intake and Loss in 4 Strains of Laboratory Mice. AB - Food availability, temperature, humidity, strain, and caging type all affect water consumption by mice. Measurement of transepidermal water loss (TEWL) is a new technique for the quantification of water turnover in mice. To understand water turnover in common strains of adult mice, male and female SCID, SKH, C57BL/6, and FVB mice were housed in same-sex groups of 5 animals in static cages or IVC. Body weight, TEWL, urine osmolality, and water consumption of mice and intracage temperature and humidity were measured every 48 h for comparison. Static cages were monitored for 7 d and IVC for 14 d before cage change. Female SCID, FVB, and C57 mice drank less water than did their male counterparts. Male and female SCID, SKH, and FVB mice in IVC drank less water and had higher urine osmolality than did those in static cages. In SCID and SKH mice, TEWL paralleled water consumption. C57 mice in static cages drank less water, had lower urine osmolality, and had less TEWL than did those in IVC. Temperature and humidity within the cage was higher than the macroenvironmental levels for all housing conditions, mouse strains, and sexes. Temperatures within IVC ranged from 76.6 to 81.4 degrees F compared with 69+/-0.4 degrees F in the room. Humidity within IVC ranged from 68% to 79% compared with 27.o%+/-2.7% within the room. These data demonstrate that mouse strain and housing conditions significantly influence water balance and indicate that macroenvironmental measurements do not always reflect the intracage environment. PMID- 27657707 TI - Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis). AB - To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status. PMID- 27657708 TI - Guidance Regarding Sample Collection and Refinement of Fecal Flotation Exam for the Isolation of Aspiculuris tetraptera. AB - Aspiculuris tetraptera continues to be a problem in rodent vivaria, in part due to difficulties in parasite detection. Although PCR testing is highly sensitive, it is expensive and does not always provide immediate results. Consequently, many institutions rely on passive fecal flotation as a quick inhouse exam for diagnosing A. tetraptera infections. To increase the sensitivity of this test, we examined multiple parameters to determine the optimal test protocol. A 30-min soaking period prior to fecal flotation for 15 min allowed fecal pellets to soften and facilitated efficient egg isolation. We also evaluated the effect of time of day, sample size, age, sex, and housing status on egg isolation. No evidence of cyclical egg shedding was found, and although larger fecal sample sizes did not result in more eggs isolated, their use reduced the incidence of false-negative exams. The most eggs were isolated from 8- and 12-wk-old mice, and as mice aged, the number of eggs isolated declined. Overall, neither sex nor housing status influenced the number of eggs isolated. Finally, examination of multiple diagnostic tests (fecal flotation exam, direct examination of cecal and colonic contents, and fecal PCR) revealed that no single test was definitive, thus indicating that multiple tests might be required to successfully screen mice with low pinworm burdens. These findings provide guidance regarding sample selection, collection, and processing to efficiently detect A. tetraptera. PMID- 27657709 TI - Intraperitoneal Continuous-Rate Infusion for the Maintenance of Anesthesia in Laboratory Mice (Mus musculus). AB - Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine-xylazine-acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine-xylazine-acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine-xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing. PMID- 27657710 TI - Effects of Ketamine on Metabolomics of Serum and Urine in Cynomolgus Macaques (Macaca fascicularis). AB - In this study, a metabolomics approach based on nuclear magnetic resonance spectroscopy and pertinent multivariate data analyses was used to evaluate the effect of ketamine on metabolic markers in cynomolgus macaques. Principal component analysis and orthogonal projection to latent structure with discriminant analysis showed that ketamine (10 mg/kg) induced metabolic perturbations. Compared with the control group, ketamine-treated macaques had lower serum levels of alpha-glucose, myoinositol, lactate and succinate and lower urine levels of pyruvate and lactate. In contrast, the levels of leucine in serum and arginine in urine were significantly higher in the ketamine group. Our results also demonstrated that a single injection of ketamine influenced the major energy and amino acid metabolic pathways in cynomolgus macaques. Our study suggests that these influences should be considered in the design of experiments and the interpretation related blood and urine data from ketamine-sedated cynomolgus macaques. PMID- 27657711 TI - Effects of Using Tricaine Methanesulfonate and Metomidate before Euthanasia on the Contractile Properties of Rainbow Trout (Oncorhynchus mykiss) Myocardium. AB - Because many anesthetics work through depressing cell excitability, unanesthetized euthanasia has become common for research involving excitable tissues (for example muscle and nerve) to avoid these depressive effects. However, anesthetic use during euthanasia may be indicated for studies involving isolated tissues if the potential depressive effects of brief anesthetic exposure dissipate after subsequent tissue isolation, washout, and saline perfusion. We explore this here by measuring whether, when applied prior to euthanasia, standard immersion doses of 2 fish anesthetics, tricaine methanesulfonate (TMS; 100 mg/L, n = 6) and methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (metomidate, 10 mg/L, n = 6), have residual effects on the contractile properties (force and work output) of isolated and saline-perfused ventricular compact myocardium from rainbow trout (Oncorhynchus mykiss). Results suggest that direct exposure of muscle to immersion doses of TMS-but not metomidate-impairs muscle contractile performance. However, brief exposure (2 to 3 min) to either anesthetic during euthanasia only-providing that the agent is washed out prior to tissue experimentation-does not have an effect on the contractile properties of the myocardium. Therefore, the use of TMS, metomidate, and perhaps other anesthetics that depress cell excitability during euthanasia may be indicated when conducting research on isolated and rinsed tissues. PMID- 27657712 TI - Comparison of Submental Blood Collection with the Retroorbital and Submandibular Methods in Mice (Mus musculus). AB - Nonterminal blood sample collection of sufficient volume and quality for research is complicated in mice due to their small size and anatomy. Large (>100 MUL) nonterminal volumes of unhemolyzed or unclotted blood currently are typically collected from the retroorbital sinus or submandibular plexus. We developed a third method-submental blood collection-which is similar in execution to the submandibular method but with minor changes in animal restraint and collection location. Compared with other techniques, submental collection is easier to perform due to the direct visibility of the target vessels, which are located in a sparsely furred region. Compared with the submandibular method, the submental method did not differ regarding weight change and clotting score but significantly decreased hemolysis and increased the overall number of high quality samples. The submental method was performed with smaller lancets for the majority of the bleeds, yet resulted in fewer repeat collection attempts, fewer insufficient samples, and less extraneous blood loss and was qualitatively less traumatic. Compared with the retroorbital technique, the submental method was similar regarding weight change but decreased hemolysis, clotting, and the number of overall high-quality samples; however the retroorbital method resulted in significantly fewer incidents of insufficient sample collection. Extraneous blood loss was roughly equivalent between the submental and retroorbital methods. We conclude that the submental method is an acceptable venipuncture technique for obtaining large, nonterminal volumes of blood from mice. PMID- 27657713 TI - Evaluation of Euthanasia Techniques for an Invertebrate Species, Land Snails (Succinea putris). AB - The euthanasia of invertebrates used in scientific investigations poses unanswered questions regarding the rapid induction of unconsciousness with minimal distress and pain. Relative to vertebrates, invertebrates' sensory experience of pain, nociception, and physiologic response to aversive stimuli are poorly characterized. The scientific communities in the European Union, Canada, United States, Australia, and New Zealand join in consensus regarding the need to address alleviation of pain and distress in cephalopods (octopus, squid, and so forth), which have the best-characterized nervous system among invertebrates. In the current study, we evaluated various euthanasia techniques in a terrestrial gastropod species, with priority on animal wellbeing, scientific variability, feasibility in both field and laboratory settings, and acceptability by personnel. In addition, we demonstrated that the 2-step method of euthanasia described in the AVMA Guidelines as acceptable for aquatic invertebrates is effective for terrestrial snails and meets all welfare and scientific requirements. This 2-step method first induces anesthesia by immersion in 5% ethanol (laboratory-grade ethanol or beer) followed by immersion in a euthanizing and tissue-preserving solution of 70% to 95% ethanol or 10% neutral buffered formalin. Furthermore, alternative methods of euthanasia for terrestrial snails commonly used in field research, such as live immersion in concentrated ethanol or formalin, were shown to be unacceptable. PMID- 27657714 TI - Evaluation of Fecal Microbiota Transfer as Treatment for Postweaning Diarrhea in Research-Colony Puppies. AB - Frequently just prior to or at weaning (approximate age, 6 to 8 wk), puppies in research settings often develop diarrheal disease, which may be due, in part, to an immature and unstable intestinal microbiota that is permissive to opportunistic pathogens. The overall objective of this study was to assess whether fecal microbiota transfer (FMT) increased the transmission of a stable maternal microbiota to pups and decreased the incidence of postweaning diarrhea. Puppies were designated by litter as treated (FMT) or sham-treated. The FMT group received fecal inoculum orally for 5 consecutive days during weaning (at 6 to 8 wk of age). Diarrhea was evaluated according to a published scoring system for 11 d during the weaning period. Fresh feces were collected from dams and puppies at 3 d before weaning and 3, 10, and 24 d after weaning for analysis of the fecal microbiota by using 16S rRNA amplicon sequencing. The composition of fecal inoculum refrigerated at 3 to 5 degrees C was stable for at least 5 d. No diarrhea was reported in either group during the study period, making comparison of treated and control groups problematic. However, 16S rRNA gene analysis revealed microbial variability across time in both groups. Therefore, although the fecal microbiota of neither group of puppies mirrored the dam at any of the designated time points, the data provided fundamental and novel information regarding the dynamic maturation process of the fecal microbiota of puppies after weaning. PMID- 27657715 TI - Comparison of Microchip Transponder and Noncontact Infrared Thermometry with Rectal Thermometry in Domestic Swine (Sus scrofa domestica). AB - During disease outbreaks, core temperature is a useful health metric in swine, due to the presence of pyrexia especially during the acute phase of infection. Despite technologic advances in other facets of swine production and health management, rectal thermometry continues to be the 'gold standard' for measuring core body temperature. However, for various reasons, collecting rectal temperatures can be difficult and unsafe depending on the housing modality. In addition, the delay between insertion of the rectal thermometer and obtaining a reading can affect measurement accuracy, especially when the pig requires physical restraint. Clearly safer, faster, and more accurate and precise temperature acquisition methods that necessitate minimal or no handling of swine are needed. We therefore compared rectal thermometers, subcutaneous microchips, and an inexpensive handheld infrared thermometer by measuring the core body temperature of 24 male castrated piglets at random intervals over a 5-wk period. The core body temperature (mean +/- 1 SD) was 39.3+/-0.5 degrees C by rectal thermometry, 39.0+/-0.7 degrees C by microchip transponder, and 34.3+/-1.0 degrees C by infrared thermometry; these 3 values differed significantly. Although the readings obtain by using infrared thermometry were numerically lower than those from the other methods, it is arguably the safest method for assessing the core temperature of swine and showed strong relative correlation with rectal temperature. PMID- 27657716 TI - The Effect of Anesthesia on Blood Pressure Measured Noninvasively by Using the Tail-Cuff Method in Marmosets (Callithrix jacchus). AB - In this study, we evaluated the validity of measuring blood pressure (BP) noninvasively in marmosets by using the tail-cuff method. The number of measurements needed for a valid reading was calculated by plotting the average SD of 5 consecutive readings in 10 naive marmosets; the SD for both systolic and diastolic BP readings plateaued after 4 readings. To evaluate how anesthesia (alphaxalone, 15 mg/kg IM) affected BP in marmosets, we measured 4 animals every minute for 60 min after injection. The average length of anesthesia was 47.3 +/- 13.2 min. The variability in the systolic and diastolic BP was the smallest at 10 to 30 min after injection (systolic SD, 6.29 mm Hg; diastolic SD, 5.27 mm Hg) and almost doubled at 30 to 60 min after injection (systolic SD, 13.5 mm Hg; diastolic SD, 12.3 mm Hg). The within- and between-session repeatability and reproducibility were calculated by measuring 12 marmosets twice at the same time of day (+/-1 h) 1 wk apart. The coefficients of repeatability and reproducibility were 1.98% and 14.5% for systolic BP and 3.37% and 16.2% for diastolic BP, respectively. Our results indicate that using the volumetric tail-cuff method to measure BP noninvasively in anesthetized marmosets is safe and feasible. The measures are least variable within 10 to 30 min after the injection of anesthetic, and variability increases slightly between sessions. PMID- 27657717 TI - Cross-Training Laboratory Animal Care Personnel in Physically Separate Animal Facilities at a Land-Grant Institution. AB - The University of Illinois at Urbana-Champaign maintains physically separated animal care facilities under centralized management by the Division of Animal Resources. As part of a land-grant institution, the animal care and use program operates several animal units in key locations for specific disciplines within the campus, all of which have the core mission to teach, conduct research, and engage in public service. Populations of research animals vary with the levels of research funding, the number of research investigators on staff, research direction, and animal availability. Accordingly, the requirement for animal care staffing in each unit may vary widely also. To best use the existing animal care staff and remain fiscally responsible, cross-training of staff was implemented to allow staff to travel from units with small animal populations to units with larger populations or short-term staffing shortages. Here we detail and describe the system we used to assess the needs for cross-training, identify the staff to train, and implement the training plan. We believe this information will assist other programs, particularly those with large or complex organization (for example, land-grant institutions) that experience similar fluctuations in animal use. PMID- 27657718 TI - Identification of Specific Effect of Chloride on the Spectral Properties and Structural Stability of Multiple Extracellular Glutamic Acid Mutants of Bacteriorhodopsin. AB - In the present work we combine spectroscopic, DSC and computational approaches to examine the multiple extracellular Glu mutants E204Q/E194Q, E204Q/E194Q/E9Q and E204Q/E194Q/E9Q/E74Q of bacteriorhodopsin by varying solvent ionic strength and composition. Absorption spectroscopy data reveal that the absorption maxima of multiple EC Glu mutants can be tuned by the chloride concentration in the solution. Visible Circular dichroism spectra imply that the specific binding of Cl- can modulate weakened exciton chromophore coupling and reestablish wild type like bilobe spectral features of the mutants. The DSC data display reappearance of the reversible thermal transition, higher Tm of denaturation and an increase in the enthalpy of unfolding of the mutants in 1 M KCl solutions. Molecular dynamics simulations indicate high affinity binding of Cl- to Arg82 and to Gln204 and Gln194 residues in the mutants. Analysis of the experimental data suggests that simultaneous elimination of the negatively charged side chain of Glu194 and Glu204 is the major cause for mutants' alterations. Specific Cl- binding efficiently coordinates distorted hydrogen bonding interactions of the EC region and reconstitutes the conformation and structure stability of mutated bR in WT like fashion. PMID- 27657719 TI - High-Resolution NMR Studies of Human Tissue Factor. AB - In normal hemostasis, the blood clotting cascade is initiated when factor VIIa (fVIIa, other clotting factors are named similarly) binds to the integral membrane protein, human tissue factor (TF). The TF/fVIIa complex in turn activates fX and fIX, eventually concluding with clot formation. Several X-ray crystal structures of the soluble extracellular domain of TF (sTF) exist; however, these structures are missing electron density in functionally relevant regions of the protein. In this context, NMR can provide complementary structural information as well as dynamic insights into enzyme activity. The resolution and sensitivity for NMR studies are greatly enhanced by the ability to prepare multiple milligrams of protein with various isotopic labeling patterns. Here, we demonstrate high-yield production of several isotopically labeled forms of recombinant sTF, allowing for high-resolution NMR studies both in the solid and solution state. We also report solution NMR spectra at sub-mM concentrations of sTF, ensuring the presence of dispersed monomer, as well as the first solid-state NMR spectra of sTF. Our improved sample preparation and precipitation conditions have enabled the acquisition of multidimensional NMR data sets for TF chemical shift assignment and provide a benchmark for TF structure elucidation. PMID- 27657720 TI - To Be Connected or Not To Be Connected? Mobile Messenger Overload, Fatigue, and Mobile Shunning. AB - With the increased adoption of mobile devices, mobile communication is all around us and we are connected anywhere, anytime. Mobile communication in general and mobile messenger service in particular make interpersonal communication in Korea so frequent and convenient. However, being connected too much anywhere and anytime via mobile messenger service appears to lead an increasing number of people to feel fatigue and to decrease mobile communication under some conditions. Based on a sample of 334 respondents, this study empirically investigated the relationships among commercial, noncommercial mobile messenger overload, mobile messenger fatigue, relational self-concept, and mobile shunning behavior. The findings show that (a) the effect of noncommercial mobile messenger overload is stronger than that of commercial mobile messenger overload in increasing mobile messenger fatigue although both positively affect mobile messenger fatigue, (b) relational self-concept has moderating effects on the relationship between mobile messenger overload and mobile messenger fatigue, and that (c) mobile messenger fatigue triggers mobile communicators' shunning behavior through which the communicators increase their intention to avoid mobile communication, to change their mobile phone numbers, and to subscribe to dual number service on one mobile device. When confronted with mobile messenger fatigue caused by mobile messenger overload, mobile messaging service users are likely to shun their mobile communication. Being constantly and conveniently connected appears to be a blessing in disguise. PMID- 27657721 TI - Assessment of the Risk of Suicide-Related Events Induced by Concomitant Use of Antidepressants in Cases of Smoking Cessation Treatment with Varenicline and Assessment of Latent Risk by the Use of Varenicline. AB - Smoking Cessation Treatment (SCT) is a policy that has to be promoted for health economics, and expectations for the success of treatments with varenicline (VAR) are large. However, the Food and Drug Administration (FDA) have issued a warning on VAR-induced depression and suicide. In the present study, utilizing the FDA Adverse Event Reporting System (FAERS), we searched for antidepressants (ADs) used during SCT that cause fewer suicide-related events (SRE) (Study 1). We also investigated whether VAR concomitantly administered with ADs increases the risk of SRE (Study 2). In addition, we investigated whether the use of VAR alone is a latent risk factor of SRE. The backgrounds of cases with and without SRE were matched using the Propensity Score. In Study 1, the highest integrated Reporting Odds Ratio (iROR) was noted in concomitantly administered mirtazapine (iROR 6.98; 95% Confidence Interval (CI) 1.57-30.99), while the lowest ratio was noted in concomitantly administered amitriptyline (iROR 0.59; iROR95%CI 0.23-1.50). Study 2 clarified that SCT increases the risk of SRE in AD-treated cases (iROR 8.02; iROR95%CI 5.47-11.76; not significance). Of ADs concomitantly used during SCT with VAR, amitriptyline and mirtazapine showed the lowest and highest risks, respectively (Study 1). It was clarified that concomitant use of VAR in the treatment of depression with ADs increased the risk of SRE (Study 2). The results of Studies 1 and 2 suggested that the use of VAR alone is a latent risk factor inducing suicide. PMID- 27657723 TI - Model Based Predictive Control of Multivariable Hammerstein Processes with Fuzzy Logic Hypercube Interpolated Models. AB - This paper introduces the Fuzzy Logic Hypercube Interpolator (FLHI) and demonstrates applications in control of multiple-input single-output (MISO) and multiple-input multiple-output (MIMO) processes with Hammerstein nonlinearities. FLHI consists of a Takagi-Sugeno fuzzy inference system where membership functions act as kernel functions of an interpolator. Conjunction of membership functions in an unitary hypercube space enables multivariable interpolation of N dimensions. Membership functions act as interpolation kernels, such that choice of membership functions determines interpolation characteristics, allowing FLHI to behave as a nearest-neighbor, linear, cubic, spline or Lanczos interpolator, to name a few. The proposed interpolator is presented as a solution to the modeling problem of static nonlinearities since it is capable of modeling both a function and its inverse function. Three study cases from literature are presented, a single-input single-output (SISO) system, a MISO and a MIMO system. Good results are obtained regarding performance metrics such as set-point tracking, control variation and robustness. Results demonstrate applicability of the proposed method in modeling Hammerstein nonlinearities and their inverse functions for implementation of an output compensator with Model Based Predictive Control (MBPC), in particular Dynamic Matrix Control (DMC). PMID- 27657722 TI - HCV Diversity among Chinese and Burmese IDUs in Dehong, Yunnan, China. AB - HCV transmission is closely associated with drug-trafficking routes in China. Dehong, a prefecture of Yunnan, is the important trade transfer station linking Southeast Asia and China, as well as the drug-trafficking channel linking "Golden triangle" and other regions of China and surrounding countries. In this study, we investigated the HCV genotype diversity among IDUs in Dehong based on 259 HCV positive samples from 118 Chinese and 141 Burmese IDUs. HCV genotypes were determined based on the phylogenies of C/E2 and NS5B genomic sequences. Six HCV subtypes, including 1a, 1b, 3a, 3b, 6n and 6u, were detected. Interestingly, 4 HCV sequences from Burmese IDUs did not cluster with any known HCV subtypes, but formed a well-supported independent clade in the phylogenetic trees of both C/E2 and NS5B, suggesting a potential new HCV subtype circulating in Dehong. Subtype 3b was the predominant subtype, followed by subtypes 6n and 6u. Comparison showed that Dehong had a unique pattern of HCV subtype distribution, obviously different from other regions of China. In particular, HCV subtypes 6u and the potential new HCV subtype had a relatively high prevalence in Dehong, but were rarely detected in other regions of China. There was no significant difference in HCV subtype distribution between Burmese and Chinese IDUs. Few HCV sequences from Burmese and Chinese IDUs clustered together to form transmission clusters. Furthermore, about half of HCV sequences from Burmese IDUs formed small transmission clusters, significantly higher than that from Chinese IDUs (p<0.01). These suggest that the Chinese and Burmese IDUs were relatively isolated from each other in injection drug use behavior and the Burmese IDUs might prefer to inject drugs themselves together. The unique genotype distribution and complex diversity of genotype 6 among IDUs may be associated with the special geographical position of Dehong. PMID- 27657724 TI - Vitamin D3 Supplementation and Antibiotic Consumption - Results from a Prospective, Observational Study at an Immune-Deficiency Unit in Sweden. AB - BACKGROUND: Vitamin D supplementation has been proposed to improve clinical symptoms during respiratory tract infections (RTIs), but results from randomized, placebo-controlled trials (RCT) are inconclusive. Previously, we performed an RCT in patients with various immune-disorders and observed that supplementation with 4000 IU vitamin D/day during 12 months significantly reduced antibiotic consumption and RTIs. This formed the basis for new guidelines at our unit; i.e. patients with insufficient levels of 25-hydroxyvitamin D (<=75 nmol/L) are now offered vitamin D supplementation. The aim of this prospective follow-up study was to evaluate the outcome of these new recommendations with regard to antibiotic consumption in our unit. METHOD: 277 patients with insufficiency were supplemented with vitamin D3, 1500-1600 IU/day for 12 months. Each patient was its own control and data on antibiotic consumption was monitored 12 months before and 12 months after initiation of vitamin D3 supplementation. RESULTS: Vitamin D3 supplementation resulted in a significantly reduced antibiotic consumption, from 20 to 15 days/patient (p<0.05). The number of antibiotic-free patients increased from 52 to 81 after vitamin D3 supplementation; OR 1.79; 95% CI 1.20-2.66 (p<0.01). The number of antibiotic-prescriptions decreased significantly, a finding that mainly was attributed to a reduction of respiratory tract antibiotics (p<0.05). Subgroup analysis showed that only patients without immunoglobulin substitution (n = 135) had a significant effect of vitamin D supplementation. CONCLUSION: Vitamin D3 supplementation of 1600 IE /day is safe to use in immunodeficient patients with 25-OHD levels less than 75 nmol/L and significantly reduced the antibiotic consumption in patients without immunoglobulin substitution. PMID- 27657725 TI - Proposed homology of the dorsomedial subdivision and V-shaped layer of the avian hippocampus to Ammon's horn and dentate gyrus, respectively. AB - The avian hippocampal formation differs considerably from that of mammals both in terms of position and cytoarchitecture. On the basis of fiber connections in pigeons, however, we previously proposed that the dorsomedial subdivision (DM) and the V-shaped layer of the hippocampal formation correspond to Ammon's horn and the dentate gyrus of mammals, respectively. In the present study, we provide evidence in support of this hypothesis by double staining hippocampal neurons using tract-tracing and gene expression. After cholera toxin subunit B (CTB) was injected into the lateral septal nucleus (SL), and vesicular glutamate transporter 2 (vGluT2) mRNA, a gene marker for glutamatergic neurons, was visualized in the same retrogradely labeled neurons with in situ hybridization, most CTB+/vGluT2+ neurons were concentrated in DM, but were rare in the V-shaped layer. The distribution pattern of CTB+/vGluT2+ neurons in the hippocampal formation did not change when CTB injection sites were shifted in a rostrocaudal direction in SL. SL expresses a variety of mRNAs for ionotropic glutamate receptor subunits (GluA1, GluA2, GluK2, GluK4, and GluN1). The findings indicate that DM neurons provide descending glutamatergic axons to SL. Additionally, the present study showed that Prox1 mRNA, a gene marker for the dentate gyrus in mammals, was intensely expressed in the V-shaped layer in the pigeon hippocampus. Together these results strengthen our original hypothesis that DM and the V shaped layer in the pigeon hippocampus are homologous to Ammon's Horn and the dentate gyrus, respectively. (c) 2016 Wiley Periodicals, Inc. PMID- 27657726 TI - Obligatory Role of EP1 Receptors in the Increase in Cerebral Blood Flow Produced by Hypercapnia in the Mice. AB - Hypercapnia induces potent vasodilation in the cerebral circulation. Although it has long been known that prostanoids participate in the cerebrovascular effects of hypercapnia, the role of prostaglandin E2 (PGE2) and PGE2 receptors have not been fully investigated. In this study, we sought to determine whether cyclooxygenase-1 (COX-1)-derived PGE2 and EP1 receptors are involved in the cerebrovascular response induced by hypercapnia. Cerebral blood flow (CBF) was recorded by laser-Doppler flowmetry in the somatosenasory cortex of anesthetized male EP1-/- mice and wild type (WT) littermates. In WT mice, neocortical application of the EP1 receptor antagonist SC-51089 attenuated the increase in CBF elicited by systemic hypercapnia (pCO2 = 50-60 mmHg). SC-51089 also attenuated the increase in CBF produced by neocortical treatment of arachidonic acid or PGE2. These CBF responses were also attenuated in EP1-/- mice. In WT mice, the COX-1 inhibitor SC-560, but not the COX-2 inhibitor NS-398, attenuated the hypercapnic CBF increase. Neocortical application of exogenous PGE2 restored the attenuation in resting CBF and the hypercapnic response induced by SC-560. In contrast, exogenous PGE2 failed to rescue the attenuation both in WT mice induced by SC-51089 and EP1-/- mice, attesting to the obligatory role of EP1 receptors in the response. These findings indicate that the hypercapnic vasodilatation depends on COX-1-derived PGE2 acting on EP1 receptors and highlight the critical role that COX-1-derived PGE2 and EP1 receptors play in the hypercapnic regulation of the cerebral circulation. PMID- 27657727 TI - Correction: Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance. AB - [This corrects the article DOI: 10.1371/journal.pone.0136486.]. PMID- 27657728 TI - Differences in Cytokine Expression and STAT3 Activation between Healthy Controls and Patients of Unexplained Recurrent Spontaneous Abortion (URSA) during Early Pregnancy. AB - Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be essential for a normal pregnancy, the precise mechanism underlying the pathogenesis of URSA remains to be fully elucidated, albeit it is known to involve inflammation. Here, we examine the relationship between the expression of inflammatory cytokines and the activation of downstream signaling pathways in URSA patients. Decidual and peripheral blood samples were collected from 30 URSA patients and from 30 women with normal early pregnancies. Western blot analysis was used to measure the expression levels of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), and interleukin-17 receptor(IL-17R) in the decidual samples. Enzyme-linked immunosorbent assay was used to assess the levels of IL-17, IL-10, IL-6, and IL-23 in the peripheral blood and decidual samples. In the URSA patients, the IL-10 expression levels were lower than those in the control subjects (P<0.05), whereas IL-6, IL-17, and IL-23 were all expressed at higher levels(P<0.05). Furthermore, the expression levels of IL-17R and p-STAT3 were higher in the URSA patients, exhibiting a trend similar to that of IL-23. Our finding of increased IL-23 expression in the deciduae and peripheral blood of patients with URSA suggest that this maybe a contributing factor to the pathogenesis of this disease. Likewise, STAT3 activation through its phosphorylation, which was associated with the IL-23 increase, may also be involved in URSA pathogenesis. However, the precise pathogenic mechanism requires further study. PMID- 27657729 TI - Standardized Reporting of Prostate MRI: Comparison of the Prostate Imaging Reporting and Data System (PI-RADS) Version 1 and Version 2. AB - INTRODUCTION: Objective of our study was to determine the agreement between version 1 (v1) and v2 of the Prostate Imaging Reporting and Data System (PI-RADS) for evaluation of multiparametric prostate MRI (mpMRI) and to compare their diagnostic accuracy, their inter-observer agreement and practicability. MATERIAL AND METHODS: mpMRI including T2-weighted imaging, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE) of 54 consecutive patients, who subsequently underwent MRI-guided in-bore biopsy were re-analyzed according to PI RADS v1 and v2 by two independent readers. Diagnostic accuracy for detection of prostate cancer (PCa) was assessed using ROC-curve analysis. Agreement between PI RADS versions and observers was calculated and the time needed for scoring was determined. RESULTS: MRI-guided biopsy revealed PCa in 31 patients. Diagnostic accuracy for detection of PCa was equivalent with both PI-RADS versions for reader 1 with sensitivities and specificities of 84%/91% (AUC = 0.91 95%CI[0.8 1]) for PI-RADS v1 and 100%/74% (AUC = 0.92 95% CI[0.8-1]) for PI-RADS v2. Reader 2 achieved similar diagnostic accuracy with sensitivity and specificity of 74%/91% (AUC = 0.88 95%CI[0.8-1]) for PI-RADS v1 and 81%/91% (AUC = 0.91 95%CI[0.8-1]) for PI-RADS v2. Agreement between scores determined with different PI-RADS versions was good (reader 1: kappa = 0.62, reader 2: kappa = 0.64). Inter observer agreement was moderate with PI-RADS v2 (kappa = 0.56) and fair with v1 (kappa = 0.39). The time required for building the PI-RADS score was significantly lower with PI-RADS v2 compared to v1 (24.7+/-2.3 s vs. 41.9+/-2.6 s, p<0.001). CONCLUSION: Agreement between PI-RADS versions was high and both versions revealed high diagnostic accuracy for detection of PCa. Due to better inter-observer agreement for malignant lesions and less time demand, the new PI RADS version could be more practicable for clinical routine. PMID- 27657731 TI - Correction: EEG Beta Power but Not Background Music Predicts the Recall Scores in a Foreign-Vocabulary Learning Task. AB - [This corrects the article DOI: 10.1371/journal.pone.0161387.]. PMID- 27657730 TI - Cerebrospinal Fluid Inflammatory Biomarkers Reflect Clinical Severity in Huntington's Disease. AB - INTRODUCTION: Immune system activation is involved in Huntington's disease (HD) pathogenesis and biomarkers for this process could be relevant to study the disease and characterise the therapeutic response to specific interventions. We aimed to study inflammatory cytokines and microglial markers in the CSF of HD patients. METHODS: CSF TNF-alpha, IL-1beta, IL-6, IL-8, YKL-40, chitotriosidase, total tau and neurofilament light chain (NFL) from 23 mutation carriers and 14 healthy controls were assayed. RESULTS: CSF TNF-alpha and IL-1beta were below the limit of detection. Mutation carriers had higher YKL-40 (p = 0.003), chitotriosidase (p = 0.015) and IL-6 (p = 0.041) than controls. YKL-40 significantly correlated with disease stage (p = 0.007), UHDRS total functional capacity score (r = -0.46, p = 0.016), and UHDRS total motor score (r = 0.59, p = 4.5*10-4) after adjustment for age. CONCLUSION: YKL-40 levels in CSF may, after further study, come to have a role as biomarkers for some aspects of HD. Further investigation is needed to support our exploratory findings. PMID- 27657732 TI - Moving Away From Spoon-Feeding as a Teaching Style in Radiology. AB - OBJECTIVE: Medical education has been an important topic in the literature, with many new attempts to revitalize and improve efforts to teach physicians and students. As a unique subspecialty that incorporates visual learning, knowledge of clinical management and presentation, basic science topics such as physics and mechanics, and procedural skills, radiology affords itself to new and more effective methods of teaching. CONCLUSION: Much of radiology education has currently focused on the concept of spoon-feeding information from the teacher to the learners. This article outlines the dangers of this approach in radiology and offers solutions for educators to improve their teaching skills and use the potential afforded by the diversity of the field. PMID- 27657734 TI - Disclosure of Sexual Orientation by Gay and Bisexual Men in Government Administered Probability Surveys. AB - PURPOSE: Researchers are increasingly using national population surveys (NPS) to understand the health of gay and bisexual men (GBM). However, valid inference from these surveys depends on accurate identification of GBM. METHODS: We asked 8126 GBM in an anonymous, online, community-recruited survey about their willingness to reveal their sexual orientation in NPS. RESULTS: Overall, 30% indicated that they would not reveal their sexual orientation; however, there were differences in frequencies according to sexual orientation, relationship status, age, HIV status, living environment, education, income, and ethnicity. CONCLUSION: NPS might not be fully representative of GBM due to misclassification errors stemming from unwillingness to disclose. PMID- 27657736 TI - Physical characterization using diffusion NMR spectroscopy. AB - NMR diffusion measurements (or dNMR) provide a powerful tool for analysis of solution organization and microgeometry of the environment by probing random molecular motion. Being a very versatile method, dNMR can be applied to a large variety of samples and systems. Here, a brief introduction into dNMR and a summary of recent advances in the field are presented. The research topics include restricted diffusion, anisotropic diffusion, polymer dynamics, solution structuring and dNMR method development. The dNMR studied systems include plants, cells (cell models), liquid crystals, polymer solutions, ionic liquids, supercooled solutions, untreated water, amino acid solutions and more. It is demonstrated how a variety of dNMR methods can be applied to a system to extract the data on particular structures present among, formed by or surrounding the diffusing particles. It is also demonstrated how dNMR methods can be developed to allow probing larger geometries, low sample concentrations and faster processes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27657735 TI - Aberrant Methylation of MGMT Promoter in HNSCC: A Meta-Analysis. AB - BACKGROUND: O6-methylguanine-DNA methyl-transferase (MGMT) gene, a DNA repair gene, plays a critical role in the repair of alkylated DNA adducts that form following exposure to genotoxic agents. MGMT is generally expressed in various tumors, and its function is frequently lost because of hypermethylation in the promoter. The promoter methylation of MGMT has been extensively investigated in head and neck squamous cell carcinoma (HNSCC). However, the association between the promoter methylation of MGMT and HNSCC risk remains inconclusive and inconsistent. Therefore, we performed a meta-analysis to better clarify the association between the promoter methylation of MGMT and HNSCC risk. METHODS: A systematical search was conducted in PubMed, Web of Science, EMBASE, and Ovid for studies on the association between MGMT promoter methylation and HNSCC. Odds ratio (ORs) and 95% confidence intervals (CI) were calculated to estimate association between MGMT promoter methylation and risk of HNSCC. The meta regression and subgroup analysis were undertaken to explore the potential sources of heterogeneity. RESULTS: Twenty studies with 1,030 cases and 775 controls were finally included in this study. The frequency of MGMT promoter methylation was 46.70% in HNSCC group and 23.23% in the control group. The frequency of MGMT promoter methylation in HNSCC group was significantly higher than the control group (OR = 2.83, 95%CI = 2.25-3.56). CONCLUSION: This meta-analysis indicates that aberrant methylation of MGMT promoter was significantly associated with the risk of HNSCC, and it may be a potential molecular marker for monitoring the disease and may provide new insights to the treatment of HNSCC. PMID- 27657733 TI - Reprogramming of mPFC transcriptome and function in alcohol dependence. AB - Despite its limited immediate reinforcement value, alcohol has a potent ability to induce neuroadaptations that promote its incentive salience, escalation of voluntary alcohol intake and aversion-resistant alcohol seeking. A constellation of these traits, collectively called 'post-dependent', emerges following brain exposure to repeated cycles of intoxication and withdrawal. The medial prefrontal cortex (mPFC) and its subdivisions exert top-down regulation of approach and avoidance behaviors, including those that lead to alcohol intake. Here, we review an emerging literature which indicates that a reprogramming of mPFC function occurs with prolonged exposure of the brain to cycles of alcohol intoxication and withdrawal. This reprogramming results in molecular dysregulations that contribute to the post-dependent syndrome. Convergent evidence has identified neuroadaptations resulting in altered glutamatergic and BDNF-mediated signaling, and for these pathways, direct evidence for a mechanistic role has been obtained. Additional evidence points to a dysregulation of pathways involving calcium homeostasis and neurotransmitter release. Recent findings indicate that global DNA hypermethylation is a key factor in reprogramming the mPFC genome after a history of dependence. As one of the results of this epigenetic remodeling, several histone modifying epigenetic enzymes are repressed. Among these, PR domain zinc-finger protein 2, a methyltransferase that selectively mono methylates histone H3 at lysine 9 has been functionally validated to drive several of the molecular and behavioral long-term consequences of alcohol dependence. Information processing within the mPFC involves formation of dynamic neuronal networks, or functional ensembles that are shaped by transcriptional responses. The epigenetic dysregulations identified by our molecular studies are likely to alter this dynamic processing in multiple ways. In summary, epigenetic molecular switches in the mPFC appear to be turned on as alcoholism develops. Strategies to reverse these processes may offer targets for disease-modifying treatments. PMID- 27657737 TI - Autologous hematopoietic cell transplantation in multiple sclerosis. AB - INTRODUCTION: Autologous haematopoietic cell transplantation (AHCT) is an evolving treatment avenue in multiple sclerosis (MS), which may be highly effective in controlling disease activity and improving disability. However, AHCT is associated with intrinsic toxicities and risks compared with conventional therapies. With growing experience in patient selection and treatment delivery, AHCT is increasingly considered an option in patients with aggressive disease that's responding poorly to disease modifying therapy. Areas covered: This article provides an introduction to AHCT and looks at its development as a treatment for MS over the last 20 years. It also highlights potential mechanisms of action, patient selection, and future trends for this treatment approach. Expert opinion: Currently published data suggest that AHCT's use is associated with significant reduction in MS disease activity and marked improvement in disability when used in patients with highly active relapsing remitting disease. Its long term safety and efficacy have not been fully evaluated but as increasing clinical trial data are published, its use is likely to grow. Further randomised controlled studies are needed to compare AHCT with standard disease modifying therapies and to optimise transplant regimens. Mechanistic studies may provide potential markers for response and a better understanding of disease pathogenesis. PMID- 27657738 TI - Demand and Congestion in Multiplex Transportation Networks. AB - Urban transportation systems are multimodal, sociotechnical systems; however, while their multimodal aspect has received extensive attention in recent literature on multiplex networks, their sociotechnical aspect has been largely neglected. We present the first study of an urban transportation system using multiplex network analysis and validated Origin-Destination travel demand, with Riyadh's planned metro as a case study. We develop methods for analyzing the impact of additional transportation layers on existing dynamics, and show that demand structure plays key quantitative and qualitative roles. There exist fundamental geometrical limits to the metro's impact on traffic dynamics, and the bulk of environmental accrue at metro speeds only slightly faster than those planned. We develop a simple model for informing the use of additional, "feeder" layers to maximize reductions in global congestion. Our techniques are computationally practical, easily extensible to arbitrary transportation layers with complex transfer logic, and implementable in open-source software. PMID- 27657739 TI - Can three-dimensional high-resolution anorectal manometry detect anal sphincter defects in patients with faecal incontinence? AB - AIM: Endoanal ultrasound (EAUS) is the gold standard for detecting anal sphincter defects in patients with faecal incontinence (FI), while anorectal manometry evaluates sphincter function. Three-dimensional high-resolution anorectal manometry (3D HRAM) is a newer modality with the potential to assess both sphincter function and anatomy. The purpose of the present study was to compare 3D HRAM with 3D EAUS for the detection of anal sphincter defects in patients with FI. METHOD: A linkage analysis was performed between the 3D HRAM and 3D EAUS databases of a tertiary referral centre to identify patients with FI who underwent both 3D EAUS and 3D HRAM. With 3D HRAM, a defect was defined as any pressure measurement below 25 mmHg at rest with at least 18 degrees of continuous expansion. The 3D HRAM findings were compared with those of 3D EAUS. RESULTS: The study cohort included 39 patients with a mean age of 64.7 +/- 15.2 years (SD); and 31 (79%) were female. Eight (21%) patients had an anal sphincter defect on EAUS with a median size of 93 degrees (range 40 degrees -136 degrees ). Fourteen (36%) had a defect shown by 3D HRAM with a median size of 144 degrees (36 degrees -180 degrees ). The sensitivity, specificity and positive and negative predictive values of 3D HRAM in detecting a sphincter defect were 75%, 74%, 43% and 92%, respectively. CONCLUSION: With a negative predictive value of 92%, 3D HRAM may be a useful screening method for ruling out a sphincter defect in patients with FI, thereby avoiding both EAUS and manometry in selected patients. PMID- 27657741 TI - Techniques and Approaches for Safe, High-Yield CT-Guided Suprahyoid Head and Neck Biopsies. AB - OBJECTIVE: The purpose of this article is to present imaging approaches and key technical, safety, and patient care best practices critical for safe, successful image-guided biopsy of head and neck masses. CONCLUSION: Image-guided sampling is an important adjunct to the diagnosis and management of head and neck masses and may be particularly useful when lesions are not accessible via an endoscope or by palpation-guided sampling. Appropriate workup is mandatory before the patient is scheduled for such a procedure. Once the procedure has been initiated, needle selection and technique are critical for increasing the diagnostic yield. Knowledge of the various head and neck biopsy approaches and their associated complications is important for optimal tissue sampling and minimization of morbidity. PMID- 27657740 TI - Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies. AB - Both preclinical and clinical studies indicate that raised intra-abdominal pressure (IAP) associated with pneumoperitoneum during laparoscopic surgical procedures can cause renal damage, the severity of which may be influenced by variables such as pressure level and duration. Several of these variables have been investigated in animal studies, but synthesis of all preclinical data has not been performed. This systematic review summarizes all available pre-clinical evidence on this topic, including an assessment of its quality and risk of bias. We performed meta-analysis to assess which aspects of the pneumoperitoneum determine the severity of its adverse effects. A systematic search in two databases identified 55 studies on the effect of pneumoperitoneum on renal function which met our inclusion criteria. There was high heterogeneity between the studies regarding study design, species, sex, pressure and duration of pneumoperitoneum, and type of gas used. Measures to reduce bias were poorly reported, leading to an unclear risk of bias in the majority of studies. Details on randomisation, blinding and a sample size calculation were not reported in >=80% of the studies. Meta-analysis showed an overall increase in serum creatinine during pneumoperitoneum, and a decrease in urine output and renal blood flow. Subgroup analysis indicated that for serum creatinine, this effect differed between species. Subgroup analysis of pressure level indicated that urine output decreased as IAP level increased. No differences between types of gas were observed. Data were insufficient to reliably assess whether sex or IAP duration modulate the effect of pneumoperitoneum. Four studies assessing long term effects indicated that serum creatinine normalized >=24 hours after desufflation of pneumoperitoneum at 15mmHg. We conclude that harmful effects on renal function and perfusion during pneumoperitoneum appear to be robust, but evidence on long-term effects is very limited. The reliability and clinical relevance of these findings for healthy patients and patients at high risk of renal impairment remain uncertain. We emphasize the need for rigorous reporting of preclinical research methodology, which is of vital importance for clinical translation of preclinical data. PMID- 27657743 TI - Screening for psychological distress in very long-term adult survivors of childhood cancer. AB - This study evaluated the prevalence of psychological distress (PD) in a cohort of 348 adult childhood cancer survivors with a very long-term follow-up and assessed the characteristics associated with this distress (cancer type, treatment, sex, age at diagnosis, self-reported late effects, social support, type of remembrance, time since the diagnosis, age at evaluation), assuming that with time since the diagnosis, the PD of survivors will approximate that of the general population. Before attending a long-term follow-up consultation, survivors were sent 3 questionnaires: the Brief Symptom Inventory-18, the Impact of Event Scale, and the Illness Worry Scale (IWS). During the visit, they were administered the Mini-International Neuropsychiatric Interview (MINI) by a psychologist. The mean age of the survivors was 38.5 years (18.1-65.8) at consultation, 7 years (0.0-18.0) at cancer diagnosis, and mean time since diagnosis was 31.5 years (8.8-56.1). Multiple regression analyses of the data collected from self-administered questionnaires confirmed that being female, living alone, and self-reported late effects were associated with the high scores for all scales. Negative remembrances and being accompanied to the clinic were associated with higher IWS scores. Unlike the initial hypothesis, the MINI showed that, compared with controls, survivors experienced a higher prevalence of anxiety and mood disorders even after a very long time since the diagnosis. These findings show that a substantial subset of survivors experiment a high prevalence of PD, higher than the general population, and should be screened for PD whatever the time since the diagnosis. PMID- 27657742 TI - In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model. AB - The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. In silico experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs' cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the in-vivo cell-killing ability of various chemotherapies. Correlation studies of such estimates with the molecular profile of patients could serve as a basis for reliable personalized predictions. PMID- 27657744 TI - The "Food Polymer Science" approach to the practice of industrial R&D, leading to patent estates based on fundamental starch science and technology. AB - This article reviews the application of the "Food Polymer Science" approach to the practice of industrial R&D, leading to patent estates based on fundamental starch science and technology. The areas of patents and patented technologies reviewed here include: (a) soft-from-the-freezer ice creams and freezer-storage stable frozen bread dough products, based on "cryostabilization technology" of frozen foods, utilizing commercial starch hydrolysis products (SHPs); (b) glassy matrix encapsulation technology for flavors and other volatiles, based on structure-function relationships for commercial SHPs; PMID- 27657747 TI - Opening ethical doors. AB - In March 1988 an 88 year old woman was admitted to a hospital suffering from bronchopneumonia. During the evening of her first day of admission a 'do not resuscitate' (DNR) decision was taken and entered into her clinical notes. The case was investigated by the Health Service Commissioner following a complaint by the patient's son who purely by chance saw the words 'not for the 222s' (a DNR order) on his mother's case notes. PMID- 27657745 TI - Cyclin A2 regulates erythrocyte morphology and numbers. AB - Cyclin A2 is an essential gene for development and in haematopoietic stem cells and therefore its functions in definitive erythropoiesis have not been investigated. We have ablated cyclin A2 in committed erythroid progenitors in vivo using erythropoietin receptor promoter-driven Cre, which revealed its critical role in regulating erythrocyte morphology and numbers. Erythroid specific cyclin A2 knockout mice are viable but displayed increased mean erythrocyte volume and reduced erythrocyte counts, as well as increased frequency of erythrocytes containing Howell-Jolly bodies. Erythroblasts lacking cyclin A2 displayed defective enucleation, resulting in reduced production of enucleated erythrocytes and increased frequencies of erythrocytes containing nuclear remnants. Deletion of the Cdk inhibitor p27Kip1 but not Cdk2, ameliorated the erythroid defects resulting from deficiency of cyclin A2, confirming the critical role of cyclin A2/Cdk activity in erythroid development. Loss of cyclin A2 in bone marrow cells in semisolid culture prevented the formation of BFU-E but not CFU-E colonies, uncovering its essential role in BFU-E function. Our data unveils the critical functions of cyclin A2 in regulating mammalian erythropoiesis. PMID- 27657748 TI - 'They told me was a fusspot'. AB - Pain management for adults has progressed rapidly during the past few years. Regrettably, the same cannot be said for pain management in children. Despite research, the whole area is beset by myths and misconceptions. Sweeping generalisations? Children quoted in a recent issue of Cascade, the magazine of Action for Sick Children beg to differ. PMID- 27657746 TI - Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy. AB - There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model (Rag2-/-IL2Rgamma-/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery (n = 26) or following a critical 3-day period (n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and alpha-smooth muscle actin. In addition, cell proliferation (anti mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved (p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair. PMID- 27657749 TI - Unions say 'job interview' for allitt witnesses is insensitive. AB - Health unions have accused managers at Grantham and Kesteven General Hospital of insensitivity in asking nurses giving evidence at the trial of Beverley Allitt to attend job interviews. PMID- 27657750 TI - 'Do not resuscitate' guidance clarified. AB - The first ever national guidelines on patient resuscitation, published last week by the Royal College of Nursing and the British Medical Association, call for appropriate consultation before doctors make 'Do not resuscitate' (DNR) decisions. PMID- 27657751 TI - Trust crisis jeopardises nurse jobs. AB - Nurse sickness levels at a Hertfordshire NHS Trust have rocketed, it was revealed last week as details of the hospital's financial crisis emerged. PMID- 27657752 TI - Chief nurse post awaits decision. AB - A decision on who will be appointed Director of Nursing for the proposed joint Guy's and St Thomas's Trust is expected within a fortnight, after the shock announcement that Guy's leader Peter Griffiths had been passed over for the Chief Executive post. PMID- 27657753 TI - Health secretary warns against delays in the closure of london hospitals. AB - Health Secretary Virginia Bottomley has warned of a 'spiral of decline' if delays occur in the planned closure of London hospitals as outlined in the government's response to the Tomlinson report. PMID- 27657755 TI - HVA/MSF race discrimination case is given the go-ahead. AB - A race discrimination case against the Health Visitors' Association/MSF can go ahead, an Industrial Tribunal has ruled. MSF claimed a tribunal application by three staff, who were all placed on the lowest secretarial grade when HVA/MSF staff scales were integrated, was out of time, but a preliminary hearing decided the case could proceed. PMID- 27657754 TI - L178,850 award for work injury. AB - A nurse who sustained serious arm and shoulder injuries in 1988 has been awarded L178,850 in compensation. The award, which is the highest ever paid to a nurse who has sustained a non-back injury, came three years after Wirral HA admitted responsibility, but gave the nurse just L2,500. PMID- 27657757 TI - Subscription news. AB - Nursing Standard annual subscription rates from April 7 will be L47 for RCN members. L55 for non-RCN members and L65 for libraries and institutions. Royal College of Nursing members can claim the full cost of their subscription against tax, reducing the cost further to L35.25. PMID- 27657759 TI - ? AB - A mass meeting of nearly 150 nurses and other health staff protesting about redundancies at lister Hospital, Hertfordshire, last week were addressed by local union officers, lip to 37 I) D to H grade nursing posts are to be axed as North Hertfordshire NHS Trust attempts to make up a cash shortfall of L1.7 million. PMID- 27657758 TI - Imminent trust axes jobs in advance. AB - At least 70 nurses last week received redundancy notices from a Trust which has not yet even come into being. PMID- 27657760 TI - New nurses only get half a chance. AB - Scotland's newly qualified nurses have only just over a 50 per cent chance of getting a job in the National Health Service, it emerged last week. PMID- 27657762 TI - The vicious circle of health staff cuts. AB - Nurses are being put on the dole at a time when more people need nursing care as the recession takes its toll, RCN General Secretary Christine Hancock has told a conference. PMID- 27657761 TI - Army nurse posts under fire. AB - Nursing posts are under threat at the Queen Elizabeth Military Hospital in Woolwich following a Ministry of Defence review of secondary care for the Armed Forces. PMID- 27657764 TI - BNA pledges no redundancies after BUPA agency takeover. AB - The British Nursing Association has taken over BUPA's nursing agency business, it was announced last week. PMID- 27657763 TI - RCN support for members who cared for Tony Bland. AB - The Royal College of Nursing has offered support to members who were caring for Tony Bland, the football fan who died last week nearly four years after being crushed in the Hillsborough Stadium disaster. PMID- 27657766 TI - ? AB - Cot death is the main concern of new parents and pregnant women, research carried out for the Health Education Authority's New Pregnancy Book shows. The book. which will be distributed free to first- time parents, has an expanded section on cot death, with guidance on laying babies down to sleep, including photographs of the safest positions. Pregnant women also worry about diet, the complications they might have during pregnancy and want more information about tests in pregnancy. Royal College of Midwives Officer Joy Moores said the book would be useful for midwives, enabling them to explore with women what choices are open to them and what support the maternity sen-ices can give'. PMID- 27657767 TI - Debate on student training. AB - Community nurses experience stress when accompanied by students, even though they enjoy taking them on their rounds, Professor Jean Orr, director of nursing at Queen's University, Belfast, told delegates at the conference. PMID- 27657769 TI - ENB government appointments announced. AB - The government appointees to the English National Board have been announced by Junior Health Minister Baroness Cumberlege. Maureen Theobald, Principal of the Nightingale and Guy's College of Nursing and Midwifery, has been named ENB Chair. One vacancy has yet to be filled. PMID- 27657770 TI - Skill mix challenge. AB - Skill mix is inevitable and should be seen as an opportunity for nurses, the first joint conference of the Health Visitors' and District Nurses Associations heard last week. PMID- 27657771 TI - Services fail ethnic minority families. AB - Nurse training should emphasise the needs of ethnic minorities, a nurse educationalist said last week, as new research showed that health care services are failing ethnic minority families. PMID- 27657773 TI - Parliament. AB - An increase in suicides, with a high proportion among Britain's unemployed, has alarmed the government. PMID- 27657774 TI - Bacterial LRTI is more common than thought. AB - Lower respiratory tract infections are far more likely to be bacterial than is generally assumed, according to new research which criticises existing strategies for managing the illness. Almost 500 adults consulting GPs at a Nottingham surgery were included in the study, which identified the pathogens involved in 91 cases. PMID- 27657772 TI - World news. AB - United States Mothers delivered by certified nurse midwives (CNMs) rather than doctors suffer less physical trauma, have shorter stays in hospital, and are less likely to be delivered prematurely, an American Nurses' Association (ANA) survey reveals. CNMs were also found to use more natural and less invasive labour and delivery procedures than doctors, and less foetal monitoring, epi-siotimies, forceps deliveries and amniotomies. They also administered less intravenous fluid. PMID- 27657775 TI - Antirheumatic drug side-effects alert. AB - Potentially fatal side-effects of slow acting antirheumatic drugs (SAARDs) mean comparative drug trials are needed to answer 'fundamental' questions about their longterm efficacy, says a report in Drug and Therapeutics Bulletin. PMID- 27657776 TI - Guidelines ignored in asthma treatment. AB - People having asthma attacks who seek help from their GPs are not being treated according to recommended guidelines, the results of a major national audit show. PMID- 27657778 TI - Start your own support group. AB - I noted Katie Wood's comments on the need tor a support group for unemployed nurses, (Finished after finals? Campaign, February 17) and wondered whether she had considered starting her own. PMID- 27657777 TI - A visionary among nurses. AB - Robert Tiffany went to The Royal Marsden in December 1967 to undertake an oncology nursing course, 27 years later he had transformed the hospital and the specialism of cancer nursing beyond recognition. His great commitment to cancer care spawned from the belief that nurses could dramatically change the care given to patients. It was a vision which drove him relentlessly forward throughout his lifetime. When he was still a junior nurse, he had an ambition to transform despair to hope tor people who had cancer. During the '70s, the mere mention of cancer instilled fear into patients, it was an immediate sentence of death. Robert began a lifelong campaign to overturn those misconceptions. He proved skilled nurses had a crucial role in preventing cancer, in early detection and improving the quality of life for people with cancer. PMID- 27657779 TI - Stub out cigarette promotions. AB - The government's 'Health of the Nation' targets call for a 30 per cent reduction in the number of adult smokers by the year 2000. But when will their policies reflect their stated aims? PMID- 27657780 TI - Practically essential. AB - Steve Flatt is not alone in having concerns about practical nursing care (Practically useless, Tradimus, February 17). PMID- 27657781 TI - Information exchange. AB - Nominations are invited for membership of the new' RCN Research Committee recently established by RCN Council. PMID- 27657782 TI - Childcare nursing is growing up. AB - Theresa Atherton warned that Project 2000-trained childcare branch nurses could find themselves unsuited to many NHS managers' requirements (Childcare nursing: the faltering first steps, Viewpoint February 10). PMID- 27657783 TI - ? AB - * I am researching the service school nurses offer in boarding secondary schools and would be most grateful if any such staff could contact me to answer a few questions about their status and duties. PMID- 27657784 TI - ? AB - * I am a staff nurse in a busy A&K department which is considering the exclusive use of documentation for nurses, in addition to the usual patient record cards. PMID- 27657785 TI - ? AB - * As nurses on a stroke rehabilitation unit, we are seeking to improve the care of patients who experience post- CVA epileptic seizures. PMID- 27657786 TI - ? AB - * I am doing a research proposal on whether student nurses under stress 'comfort eat'. I am having difficulty finding information and would be grateful for help. PMID- 27657787 TI - ? AB - * I am undertaking a study into the use of nursing models in endoscopy units and would be grateful for information from nurses in other units using a nursing model to enhance their patient care. PMID- 27657788 TI - ? AB - * We are staff nurses on a large district teaching hospital's long-stay psychogeriatric unit who have begun part-time posts - working three days on the ward and two days liaising with residential care homes offering advice, education and support to employees. PMID- 27657789 TI - Points of view. AB - The words carried in the United Kingdom Central Council's recent information to prospective candidates for its elections have a fine ring to them: 'The Council's functions are concerned with serving the public interest and protecting the vulnerable public - not that of serving the interests of the profession it regulates.' PMID- 27657790 TI - Network Factfile. PMID- 27657791 TI - Stop smoking Stop smoking Kingsley P Macdonald Optima 202pp L3.99 0-356-20125-2. AB - Stop Smoking: Understanding and Overcoming Your Addiction is an unusual book. Dr Patrick Kingsley states in the introduction 'Most importantly: Do not stop smoking yet.' He also recommends a technique which involves not smoking for five days and then chain smoking the next day. Dr Kingsley also stresses the link between diet and smoking. PMID- 27657792 TI - Women's madness J Ussher Women's madness Harvester Wheatsheaf 342pp L13.50 0-7450 0832-1. AB - Women's Madness: Misogyny or Mental Illness? is an extremely interesting book that examines the experiences of women with depression and the way that society deals with women's mental distress. It looks at two opposing viewpoints. PMID- 27657793 TI - How to survive in spite of your parents M Reinbold Cedar 242pp L5.99 0-7493-1041 3 [Formula: see text]. AB - Damaged children become damaged grownups, subconsciously re-enacting the traumas of childhood physical, sexual or emotional abuse in their adult relationships. Psychotherapy, the least understood and most feared of all medical disciplines, helps people experiencing relationship difficulties to understand themselves and their reactions to stress and external stimuli and to obtain freedom from the perpetuating legacies of guilt, morality and conscience. PMID- 27657794 TI - The rehabilitation of people with AIDS. AB - I believe that there are two very good reasons which make me a suitable person to present this paper. The first is that for the past four years I have been director of the Marie Curie Rehabilitation Centre at The Royal Marsden Hospital in London, which is an integrated unit and the first of its kind in Europe, and possibly the world. The second reason is because I am a person living with AIDS. PMID- 27657796 TI - The Hidden Cost of AIDS The Hidden Cost of AIDS Dossier Panos Panos 168pp L9-95 1 870670-29-9 [Formula: see text]. AB - In some parts of the world, AIDS is known rather aptly as the 'family disease'. Although definitions of 'the family' vary according to culture, all societies have some form of kinship network that HIV, if introduced, can wreak socioeconomic havoc with at local and national level. PMID- 27657795 TI - AIDS and HIV word search. PMID- 27657797 TI - CAREER listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Hatrow, Middlesex HA 1 2AX. Pax: 081-423 3867. PMID- 27657798 TI - Effectiveness of PTSD telehealth treatment in a VA clinical sample. AB - Over the past decade, the Veterans Health Administration has supported multiple national rollouts of evidence-based treatments for mental health disorders. Recent studies have shown, however, that the majority of veterans with mental health diagnoses are not utilizing psychotherapy services. In this article, we attempt to address one of the more commonly known barriers to treatment, distance to care. We do this by comparing the effectiveness of outpatient and telehealth cognitive processing therapy (CPT) and prolonged exposure (PE) Therapy for posttraumatic stress disorder (PTSD) in a Veteran clinical sample. Multilevel modeling analyses revealed statistically significant differences between the outpatient and telehealth treatments once baseline demographic and symptom severity differences were taken into account. Given that a number of randomized control studies have not found similar outcome differences, future research would benefit from examining whether the outcomes differences in the present study are because of treatment delivery method or sample differences. Veterans completing treatment via outpatient and telehealth delivery methods achieved clinically significant change in PTSD from pre- to posttreatment. These results suggest that delivering evidence-based treatment for PTSD via telehealth may be a viable treatment option for veterans who cannot easily access care because of geographic distance. (PsycINFO Database Record PMID- 27657799 TI - eEduHeart I: A Multicenter, Randomized, Controlled Trial Investigating the Effectiveness of a Cardiac Web-Based eLearning Platform - Rationale and Study Design. AB - OBJECTIVES: Cardiac telerehabilitation includes, in its most comprehensive format, telemonitoring, telecoaching, social interaction, and eLearning. The specific role of eLearning, however, was seldom assessed. The aim of eEduHeart I is to investigate the medium-term effectiveness of the addition of a cardiac web based eLearing platform to conventional cardiac care. METHODS: In this prospective, multicenter randomized, controlled trial, 1,000 patients with coronary artery disease will be randomized 1:1 to an intervention group (receiving 1-month unrestricted access to the cardiac eLearning platform in addition to conventional cardiac care) or to conventional cardiac care alone. The primary endpoint is health-related quality of life, assessed by the HeartQoL questionnaire at the 1- and 3-month follow-ups. Secondary endpoints include pathology-specific knowledge and self-reported eLearning platform user experience. Data on the eLearning platform usage will be gathered through web logging during the study period. RESULTS: eEduHeart I will be one of the first studies to report on the added value of eLearning. CONCLUSIONS: If the intervention is proven effective, current cardiac telerehabilitation programs can be augmented by including eLearning, too. The platform can then be used as a model for other chronic diseases in which patient education plays a key role. PMID- 27657800 TI - "You don't know until you get there": The positive and negative "lived" experience of parenting an adult child with 22q11.2 deletion syndrome. AB - OBJECTIVES: 22q11.2 deletion syndrome (22q11DS), a complex genetic syndrome associated with more than 180 features, presents complex challenges for parents including gaining a diagnosis. This phenomenological study sought the "lived" interpretations of parents supporting an adult child with 22q11DS, a poorly researched area. METHOD: Interpretative phenomenological analysis informed a detailed and open exploration of parenting a child through to adult life with 22q11DS. Using in-depth semistructured interviews, 8 parents (2 male, 6 female) of adult children with 22q11DS were individually interviewed; providing the data set for transcription and thematic analysis. RESULTS: Losing "I" Finding "self," overarched 6 subordinate themes that emerged from participants' articulated descriptions of psychological distress and psychological growth. Distress in parenting a child with 22q11DS was experienced through stigma, loss, grief, and guilt. Progressively, stigma undermined independence, friendships, and instinctual judgement. Ill-informed hierarchical structures experienced as layers of obstruction and lack of awareness of the syndrome triggered angry advocacy for their child. Diagnosis brought opposing relief and grief. In time, they came to value their unique "accomplishments," collected on their journey with 22q11DS, and in turn, consciously valued authentic "self" expressed through empathy, humility, gratitude, and pride. CONCLUSION: Parental distress through societal, educational, and health care invalidation persisted for decades for all participants. Conversely, distress facilitated psychological growth for redefining "self" and role as parents over time. Building on this phenomenological cameo, future research can educate against the plight of 22q11DS families. It can enlighten health care professionals in buffering against associated stigma, blame, and self-doubt, and in fostering psychological well being. (PsycINFO Database Record PMID- 27657801 TI - A systematic review of factors that contribute to nocebo effects. AB - OBJECTIVES: Medication side effects are common, often leading to reduced quality of life, nonadherence, and financial costs for health services. Many side effects are the result of a psychologically mediated "nocebo effect." This review identifies the risk factors involved in the development of nocebo effects. METHOD: Web of Science, Scopus, MEDLINE, PsycINFO, Journals@Ovid full text, and Global Health were searched using the terms "nocebo" and "placebo effect." To be included, studies must have exposed people to an inert substance and have assessed 1 or more baseline or experimental factor(s) on its ability to predict symptom development in response to the inert exposure. RESULTS: Eighty-nine studies were included; 70 used an experimental design and 19 used a prospective design, identifying 14 different categories of risk factor. The strongest predictors of nocebo effects were a higher perceived dose of exposure, explicit suggestions that the exposure triggers arousal or symptoms, observing people experiencing symptoms from the exposure, and higher expectations of symptoms. CONCLUSIONS: To reduce nocebo induced symptoms associated with medication or other interventions clinicians could reduce expectations of symptoms, limit suggestions of symptoms, correct unrealistic dose perceptions, and reduce exposure to people experiencing side effects. There is some evidence that we should do this especially for persons with at-risk personality types, though exactly which personality types these are requires further research. These suggestions have a downside in terms of consent and paternalism, but there is scope to develop innovative ways to reduce nocebo effects without withholding information. (PsycINFO Database Record PMID- 27657802 TI - Occurrence and co-occurrence of nonsuicidal self-injury and disordered eating in a daily diary study: Which behavior, when? AB - Although research has explored between-person traits that may account for the co occurrence of non-suicidal self-injury (NSSI) and disordered eating (DE), little is known about within-person processes that predict when each behavior occurs. This study describes the socioemotional contexts of NSSI and DE behaviors during a two-week daily diary period. Young adults (aged 18-35) who reported >=1 episode of NSSI and >=1 episode of DE (binge eating, purging, or fasting) during the diary period were included (N=25). NSSI and DE co-occurred approximately one third of the time. Participants were more likely to act on NSSI thoughts following arguments and feelings of rejection. They were more likely to act on binge eating/purging thoughts after eating or watching television, and when they felt self-hatred. They were more likely to act on fasting thoughts after discussing upsetting memories, and when they were in a public setting. NSSI days were marked by more intense negative mood in the evenings relative to fasting days, and greater fatigue in the morning relative to binge eating/purging days. This study underscores the utility of using experience-sampling methods to develop and test within-person models to advance our understanding of co occurring behaviors. PMID- 27657803 TI - Expression of positive emotions differs in illness and recovery in anorexia nervosa. AB - People with Anorexia Nervosa (AN) display reduced facial expression of emotions. This study investigated the expression of positive affect in response to a film, examining Duchenne and non-Duchenne smiles in 20 women who have recovered from AN (REC), 20 with acute AN and 20 healthy controls (HC). The results indicated that the REC group exhibited Duchenne and non-Duchenne smiles with higher duration and intensity than the AN group, comparable to the HC group. The findings warrant longitudinal studies to confirm that reduced expressivity is linked to acute AN, ameliorating after recovery. PMID- 27657804 TI - Familial covariation of facial emotion recognition and IQ in schizophrenia. AB - Alterations in general intellectual ability and social cognition in schizophrenia are core features of the disorder, evident at the illness' onset and persistent throughout its course. However, previous studies examining cognitive alterations in siblings discordant for schizophrenia yielded inconsistent results. Present study aimed to investigate the nature of the association between facial emotion recognition and general IQ by applying genetically sensitive cross-trait cross sibling design. Participants (total n=158; patients, unaffected siblings, controls) were assessed using the Benton Facial Recognition Test, the Degraded Facial Affect Recognition Task (DFAR) and the Wechsler Adult Intelligence Scale III. Patients had lower IQ and altered facial emotion recognition in comparison to other groups. Healthy siblings and controls did not significantly differ in IQ and DFAR performance, but siblings exhibited intermediate angry facial expression recognition. Cross-trait within-subject analyses showed significant associations between overall DFAR performance and IQ in all participants. Within-trait cross sibling analyses found significant associations between patients' and siblings' IQ and overall DFAR performance, suggesting their familial clustering. Finally, cross-trait cross-sibling analyses revealed familial covariation of facial emotion recognition and IQ in siblings discordant for schizophrenia, further indicating their familial etiology. Both traits are important phenotypes for genetic studies and potential early clinical markers of schizophrenia-spectrum disorders. PMID- 27657805 TI - Science for life - Recent advances in biochemical and biophysical methods. PMID- 27657807 TI - New potent biaryl sulfate-based hepatitis C virus inhibitors. AB - The discovery of a new series of potent hepatitis C virus (HCV) NS5A inhibitors containing biaryl sulfone or sulfate cores is reported. Structure-activity relationship (SAR) studies on inhibitors containing various substitution patterns of the sulfate or sulfone core structure established that m-,m'- substituted biaryl sulfate core-based inhibitors containing an amide moiety (compound 20) or an imidazole moiety (compound 24) showed extremely high potency. Compound 20 demonstrated double-digit pM potencies against both genotype 1b (GT-1b) and 2a (GT-2a). Compound 24 also exhibited double-digit pM potencies against GT-1b and sub nM potencies against GT-2a. Furthermore, compounds 20 and 24 exhibited no cardiotoxicity in an hERG ligand binding assay and showed acceptable plasma stability and no mutagenic potential in the Ames test. In addition, these compounds showed distinctive additive effects in combination treatment with the NS5B targeting drug sofosbuvir (Sovaldi(r)). The results of this study showed that the compounds 20 and 24 could be effective HCV inhibitors. PMID- 27657808 TI - Synthesis, characterization and molecular docking studies of substituted 4 coumarinylpyrano[2,3-c]pyrazole derivatives as potent antibacterial and anti inflammatory agents. AB - A green, eco-friendly and efficient protocol has been developed and synthesized a series of coumarin based pyrano[2,3-c]pyrazole derivatives (3) by multi-component reaction (MCR). Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (4) have been isolated by the reaction of compound (3) in acidic conditions. Further, intramolecular cyclization of compounds (4) leads to C4C4 chromons (9) and these compounds were screened for their biological activities using array of techniques. Most of the compounds exhibited promising antibacterial activity, in particular Gram-positive bacteria. The anti-inflammatory assay was evaluated against protein denaturation as well as HRBC membrane stabilization methods and compounds exhibit excellent anti-inflammatory activity in both methods. Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising. PMID- 27657809 TI - Targeting telomerase with radiolabeled inhibitors. AB - The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123I radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50 of 1.58 MUM (MST-312 IC50: 0.23 MUM). Clonogenic assays showed a dose dependant effect of 123I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. PMID- 27657810 TI - Tetracyclic indolines as a novel class of beta-lactam-selective resistance modifying agent for MRSA. AB - Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relationships of a novel class of RMAs, tetracyclic indolines. These selectively potentiate beta-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) without antibacterial or beta-lactamase inhibitory activity on their own. The most potent analogue, 6a, showed strong potentiation of amoxicillin/clavulanic acid in a variety of hospital-acquired and community acquired MRSA strains with low mammalian toxicity. These compounds may be further developed to extend the clinic life span of beta-lactam antibiotics. PMID- 27657811 TI - Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors. AB - In the current work, new benzodioxole-based dithiocarbamate derivatives were synthesized via the reaction of N-(1,3-benzodioxol-5-ylmethyl)-2-chloroacetamide with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. These derivatives were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. N-(1,3-Benzodioxol-5-ylmethyl)-2-[4 (4-nitrophenyl)-1-piperazinylthiocarbamoylthio]acetamide (10) can be identified as the most promising anticancer agent against C6 cell line due to its notable inhibitory effect on C6 cells with an IC50 value of 23.33 +/- 7.63 MUg/mL when compared with cisplatin (IC50 = 19.00 +/- 5.29 MUg/mL). On the other hand, compound 10 did not show any significant cytotoxic activity against A549 cell line. The compounds were also tested for their in vitro inhibitory effects on hCA I and hCA-II. Generally, the tested compounds were more effective on CAs than acetazolamide, the reference agent. Among these compounds, N-(1,3-benzodioxol-5 ylmethyl)-2-[(morpholinyl)thiocarbamoylthio]acetamide (3) and N-(1,3-benzodioxol 5-ylmethyl)-2-[(thiomorpholinyl)thiocarbamoylthio]acetamide (4) were found to be the most effective compounds on hCA-I with IC50 values of 0.346 nM and 0.288 nM, and hCA-II with IC50 values of 0.287 nM and 0.338 nM, respectively. PMID- 27657812 TI - Synthesis of novel 15-membered 8a-azahomoerythromycin A acylides: Consequences of structural modification at the C-3 and C-6 position on antibacterial activity. AB - A novel series of 6-O-substituted 8a-aza-8a-homoerythromycin A 3-O-acylides has been discovered with potent activity against key respiratory pathogens, including those inducibly and constitutively resistant to erythromycin. The best compounds in this series 15na and 15nd showed activity comparable to telithromycin, especially against Haemophilus influenzae and constitutively MLSB-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes. Furthermore, 15na exhibited a number of drug-like attributes including favorable pharmacokinetic properties and in vivo efficacy. For instance, 15na exhibited good oral bioavailability (average F = 42%) and demonstrated in vivo efficacy superior to telithromycin (1) against erythromycin-susceptible S. pneumoniae. As such, 15na has a significant potential for further development of this novel macrolide antibiotics class. PMID- 27657813 TI - Preparation and characterization of electrospun alginate/PLA nanofibers as tissue engineering material by emulsion eletrospinning. AB - Scaffolds made by biomaterials offer favorite environment for cell grow and show a wide potential application in tissue engineering. Novel biocompatibility materials polylatic acid (PLA) nanofiber membranes with favorable biocompatibility and good mechanical strength could serve as an innovative tissue engineering scaffold. Sodium alginate (SA) could be used in biomedical areas because of its anti-bacterial property, hydrophilicity and biocompatibility. In this article, we chose PLA as continuous phase and SA as dispersion phase to prepare a W/O emulsion and then electrospun it to get a SA/PLA composite nanofiber membranes. The CLSM images illustrated that the existence of SA was located on the surface of composite fibers and the FTIR results confirmed the result. A calcium ion replacement step was used as an after-treatment for SA/PLA nanofiber membranes in order to anchor the alginic ion in a form of gelated calcium alginate (CA). The single fiber tensile test shows a good mechanical property of CA/PLA nanofiber membranes, and the nanofiber membranes are beneficial for cell proliferation and differentiation owing to MTT array as well as Alizarin red S (ARS) staining test. PMID- 27657814 TI - Screening of 1300 organic micro-pollutants in groundwater from Beijing and Tianjin, North China. AB - Groundwater contamination in China has become a growing public concern because of the country's rapid economic development and dramatically increasing fresh water demand. However, there is little information available on groundwater quality, particularly with respect to trace organic micro-pollutants contamination. This study was undertaken to investigate the occurrence of 1300 pollutants at 27 groundwater sites in Beijing and Tianjin, North China. Seventy-eight chemicals (6% of the targeted compounds) were detected in at least one sampling point; observed chemicals included polycyclic aromatic hydrocarbons (PAHs), pesticides, plasticizers, antioxidants, pharmaceuticals and other emerging compounds. Chemicals with a frequency of detection over 70% were 2-ethyl-1-hexanol (median concentration 152 ng L-1), benzyl alcohol (582 ng L-1), 2-phenoxy-ethanol (129 ng L-1), acetophenone (74 ng L-1), pentamethylbenzene (51 ng L-1), nitrobenzene (40 ng L-1) and dimethyl phthalate (64 ng L-1). Pesticides with concentrations exceeding the EU maximum residual limits (MRL) of 0.1 MUg L-1 were 1,4 dichlorobenzene, oxadixyl, diflubenzuron, carbendazim, diuron, and the E and Z isomers of dimethomorph. Naphthalene and its 7 alkylated derivatives were widely observed at maximum concentration up to 30 MUg L-1, which, although high, is still below the Australian drinking water guidelines of 70 MUg L-1. The risk assessment indicated there is no human health risk through the oral consumption from most wells, although there were four wells in which total seven compounds were found at the concentrations with a potential adverse health effects. This work provides a wide reconnaissance on broad spectrum of organic micro contaminants in groundwater in North China. PMID- 27657815 TI - Highly stable and magnetically separable alginate/Fe3O4 composite for the removal of strontium (Sr) from seawater. AB - In this study, a highly stable alginate/Fe3O4 composite was synthesized, and systematically investigated for the practical application of strontium (Sr) removal in complex media, such as seawater and radioactive wastewater. To overcome the drawbacks of the use of alginate microspheres, high contents of alginic acid and Fe3O4 were used to provide a more rigid structure with little swelling and facile separation, respectively. The synthesized composite was optimized for particle sizes of <400 MUm and 1% content of Fe3O4. The alginate/Fe3O4 composite showed excellent Sr uptake (~400.0 mg/g) and exhibited outstanding selectivity for Sr among various cations (Na, Mg, Ca and K). However, in diluted Sr condition (50 mg/L), Ca significantly affected Sr adsorption, resulting in a decrease of Kd value from 3.7 to 2.4 at the 0.01 M Ca. The alginate/Fe3O4 composite could be completely regenerated using 0.1 M HCl and CaCl2. In real seawater spiked with 50 mg/L of Sr, the alginate/Fe3O4 composite showed 12.5 mg/g of Sr uptake, despite the highly concentrated ions in seawater. The adsorption experiment for radio-active 90Sr revealed a removal efficiency of 67% in real seawater, demonstrating the reliability of the alginate/Fe3O4 composite. PMID- 27657816 TI - Positive and negative electrospray ionization analyses of the organic fractions in raw and oxidized oil sands process-affected water. AB - This work investigated the oxidative transformation of the organic species in oil sands process-affected water (OSPW) using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in both negative and positive electrospray ionization (ESI) modes. This is the first time to apply FTICR-MS to investigate species transformation in OSPW treatments by ferrate (VI), UV/H2O2, and molecular ozone, and also this is the first preliminary study to use positive ESI to investigate organic species in addition to naphthenic acids (NAs) in these treatment processes. The oxidation processes with potassium ferrate (VI), UV/H2O2, and ozone transformed the distribution profiles of Ox, OxSy, and OxNy organic fractions (i.e., species containing oxygen, sulfur, and nitrogen, with x, y specifying the oxygen number and sulfur/nitrogen number, respectively), with OxSy distribution profiles showing the most sensitive responses to the oxidation extent and can be used as a signature fraction to evaluate the oxidation effectiveness. Negative mode UPLC-TOF-MS confirmed the transformation pattern of Ox species observed with FTICR-MS, but positive mode UPLC-TOF-MS results showed severe discrepancies with FTICR-MS results and should be subjected for future further investigation, regarding the relatively low mass resolution of UPLC-TOF-MS. The investigation of the transformation patterns of different organic species using two ionization modes was a preliminary study to enhance the understanding of the efficiency, selectivity, and mechanism of different oxidation processes in OSPW remediation for both NAs and non-NA species. PMID- 27657818 TI - Toxicity and physiological effect of quercetin on generalist herbivore, Spodoptera litura Fab. and a non-target earthworm Eisenia fetida Savigny. AB - A novel flavonoid, quercetin, was isolated from the medicinal plant Euphorbia hirta L. through chromatography techniques including: TLC, Column chromatography, NMR and then screened for toxicity to larvae of Spodoptera litura Fab. Bioassays were used to analyze pupal weight, survival rate, fecundity, egg hatchability, population growth index, Nutritional index and histopathology of treated larvae at a range of E. hirta extract concentrations. Results of toxicity assays demonstrated that, 6 ppm of quercetin caused 94.6% mortality of second, 91.8% of third, 88% of fourth, and 85.2% of fifth instars respectively. The lethal concentrations (LC50 and LC90) was calculated as 10.88 and 69.91 ppm for fourth instar larvae. The changes in consumption ratio and approximate digestibility produced a reduction in growth rates. Histopathology examinations revealed that the cell organelles were severely infected. Analyses of earthworm toxicity effects resulted in significantly lower rates compared to synthetic insecticides (chloropyrifos and cypermethrin). These results suggests that the botanical compound (quercetin), could have a part as a new biorational product which provides an ecofriendly alternative. Validation of the potential of quercetin, still needs to be demonstrated under field conditions, where formulation will be important in maintaining the activity. PMID- 27657817 TI - NO2 inhalation causes tauopathy by disturbing the insulin signaling pathway. AB - Air pollution has been evidenced as a risk factor for neurodegenerative tauopathies. NO2, a primary component of air pollution, is negatively linked to neurodegenerative disorders, but its independent and direct association with tau lesion remains to be elucidated. Considering the fact that the insulin signaling pathway can be targeted by air pollutants and regulate tau function, this study focused on the role of insulin signaling in this NO2-induced tauopathy. Using a dynamic inhalation treatment, we demonstrated that exposure to NO2 induced a disruption of insulin signaling in skeletal muscle, liver, and brain, with associated p38 MAPK and/or JNK activation. We also found that in parallel with these kinase signaling cascades, the compensatory hyperinsulinemia triggered by whole-body insulin resistance (IR) further attenuated the IRS-1/AKT/GSK-3beta signaling pathway in the central nervous system, which consequently increased the phosphorylation of tau and reduced the expression of synaptic proteins that contributed to the development of the tau pathology. These findings provide new insight into the possible mechanisms involved in the etiopathogenesis of NO2 induced tauopathy, suggesting that the targeting of insulin signaling may be a promising therapeutic strategy to prevent this disease. PMID- 27657819 TI - Tetrabromobisphenol A photoelectrocatalytic degradation using reduced graphene oxide and cerium dioxide comodified TiO2 nanotube arrays as electrode under visible light. AB - Tetrabromobisphenol A, one of the most important brominated retardants, is an typical persistent organic pollutant and it is of great value to develop rapid and effective degradation method. Present study established a photoelectrodegradation method with CeO2 and reduced graphene oxide co-modified TiO2 nanotube arrays (RGO-CeO2-TiO2 NAs), which were successfully synthesized and characterized with scanning electron microscopy (SEM) and Energy Dispersive X Ray Spectrometry (EDX). The SEM Images revealed that the nanotubes had a diameter of about 100 nm and an obvious layer of CeO2 and RGO on the surface of TiO2 nanotube arrays. The EDX data exhibited the presence of Ce element. The results demonstrated that TBBPA was degraded at a high degradation rate constant of 0.0191 min-1, and photogenerated holes played a major role in the degradation reaction. Significant decrease of degradation efficiency was achieved with the presence of EDTA-2Na(hole scavenger), yet while the existence of t-BuOH(OH scavenger) resulted in less inhibition on the degradation. Besides, RGO-CeO2-TiO2 NAs exhibited good stability with rarely decline of degradation efficiency for ten reused runs. All these indicated that RGO-CeO2-TiO2 NAs were a good catalyst with extraordinary catalytic activity and stability for PEC degradation, and would have great potential in the control and removal of pollutants. PMID- 27657820 TI - DGGE diversity of manganese mine samples and isolation of a Lysinibacillus sp. efficient in removal of high Mn (II) concentrations. AB - Manganese contamination has become a serious environmental problem in the world and bacterial removal plays an important role in global cycling of manganese. In this study, microorganism distribution within samples from a manganese mine was analyzed with PCR-DGGE technology. The results suggested that Manganese oxidizing bacteria (such as Bacillus, Hyphomicrobiaceae and Erythrobacter) were dominant in the soil. In addition, a Lysinibacillus sp. Isolate, strain MK-1, revealed robust growth at high Mn(II) concentrations up to 1 mM. At that concentration, 55.94% of added Mn(II) was oxidized and 36.23% of the Mn(II) was adsorbed by MK-1(total manganese removal reached 94.67%) after 7 days of culturing. By measuring its metabolic process, the great role of biological adsorption was found. Additionally, the spectroscopic result demonstrated that Mn(III) was an intermediate during the biological oxidation process. These findings increase the knowledge of biological manganese removal mechanisms and show some potentials to the operation of manganese treatment. PMID- 27657821 TI - Considering ionic state in modeling sorption of pharmaceuticals to sewage sludge. AB - Information on the partitioning of chemicals between particulate matter and water in sewage treatment plants (STPs) can be used to predict their subsequent environmental fate. However, this information can be challenging to acquire, especially for pharmaceuticals that are frequently present in ionized forms. This study investigated the relationship between the ionization state of active pharmaceutical ingredients (APIs) and their partitioning between water and sludge in STPs. We also investigated the underlying mechanisms of sludge sorption by using chemical descriptors based on ionized structures, and evaluated the usefulness of these descriptors in quantitative structure-property relationship (QSPR) modeling. KD values were collected for 110 APIs, which were classified as neutral, positive, or negative at pH 7. The models with the highest performance had the R2Y and Q2 values of above 0.75 and 0.65, respectively. We found that the dominant intermolecular forces governing the interactions of neutral and positively charged APIs with sludge are hydrophobic, pi-pi, and dipole-dipole interactions, whereas the interactions of negatively charged APIs with sludge were mainly governed by covalent bonding as well as ion-ion, ion-dipole, and dipole-dipole interactions; hydrophobicity-driven interactions were rather unimportant. Including charge-related descriptors improved the models' performance by 5-10%, underlining the importance of electrostatic interactions. The use of descriptors calculated for ionized structures did not improve the model statistics for positive and negative APIs, but slightly increased model performance for neutral APIs. We attribute this to a better description of neutral zwitterions. PMID- 27657822 TI - Abdominal tuberculosis that masked under the early postoperative septic complications. AB - INTRODUCTION: At the same time even laparoscopic adrenalectomy can become the source or the causing factor of a number of complications. In the following report we present the clinic case of diagnostic complications during postsurgical period of "rapid" development and signs of tuberculosis after laparoscopic adrenalectomy. PRESENTATION OF CASE: The patient underwent ultrasonography and CT was found out: the tumor of right adrenal gland. Operational treatment: right laparoscopy adrenalectomy. Pathologistological conclusion: clear cell adenoma. On the fourth day there was a high temperature rise noted 38-39 degrees C. On the 10th day the CT, where there were no signs of free liquid abscess formation. Relaparoscopic: small amount of serous-hemorrhagic liquid in small pelvis, hyperemated peritoneum, in both - left and right liver lobes tight knots of white color. After, the patient still had hyperthermia 38 degrees C. Phthisiatrician consulted the patient and diagnosed abdominal tuberculosis. After six-month treatment the patient in satisfactory condition was discharged home. DISCUSSION: But in case of our patient's case such visual diagnostic methods, such as CT and ultrasonography of abdominal cavity appeared to be non-informative in lymph system diagnostics due to the number of reasons.The described clinical case and literature data prove the fact, that crucial in abdominal tuberculosis form management treatment is a diagnostic laparoscopy with tissue biopsy. CONCLUSION: Labors, as well as adrenalectomy are possible factors which decrease the immunity and can cause the activation of tuberculosis process. Diagnostic laparoscopy and intraoperative histological tissue study of abdominal cavity are the main points in prescribing diagnosis of abdominal tuberculosis form. PMID- 27657823 TI - Stomaplasty with pannicuectomy in an obese patient with stomal retraction: A case report. AB - INTRODUCTION: Stomal retraction is a common complication following stoma formation. A repeat surgical procedure for stomal revision is an invasive treatment that is often required as a result. CASE PRESENTATION: An 81-year-old woman with obstructive rectal carcinoma and perforative peritonitis underwent an emergent anterior resection and colostomy (Hartmann's operation). After the operation, the patient changed the stoma pouch every day because of stomal retraction and leakage. Thirty-eight days after the operation, we performed a stomaplasty with pannicuectomy. Following this procedure, the patient changed the stoma pouch twice weekly. DISCUSSION: Stomal retraction is caused by the thick subcutaneous fat and abnormal skin folds in obese patients, as well as the excess tension that is the result of inadequate mobilization. Treatment of stomal retraction typically requires an intraperitoneal stoma revision. Our method of panniculectomy with skin excision but without stomal revision does not involve an incision around the stoma and there is no risk of fecal contamination. CONCLUSION: We report a case of an obese patient who underwent stomaplasty with pannicuectomy for stomal retraction. We believe that stomaplasty with pannicuectomy is a feasible option in obese patients with stomal retraction. PMID- 27657824 TI - Upregulation of miR-124 by physcion 8-O-beta-glucopyranoside inhibits proliferation and invasion of malignant melanoma cells via repressing RLIP76. AB - Melanoma is the most malignant type of skin cancer. In recent years, mounting studies have evidenced the involvement of miRNAs in melanoma. One of these miRNAs, miR-124 has been found aberrantly downregulated in a variety of human malignancies. In this study, our results showed that the expression of miR-124 was significantly lower in malignant melanoma tissues and cell lines and miR-124 functioned as a tumor suppressor in melanoma. Moreover, our findings showed that miR-124 exerted anti-tumor effect by directly targeting RLIP76, a stress inducible non-ABC transporter that plays a crucial role in the development of melanoma. Furthermore, our study also showed that physcion 8-O-beta glucopyranoside, a natural compound from medicinal plant, could inhibit the proliferation and invasion of melanoma cells by targeting miR-124/RLIP76 signaling. PMID- 27657825 TI - Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating Notch signaling. AB - OBJECTIVE: Curcumin as an effective anticancer bioactive extract has been proved to induce apoptosis in many cancer cells. Notch signaling regulates prostate cancer apoptosis, but it is still unknown whether curcumin induces apoptosis in DU-145 cells by regulating Notch pathway. The aim of this study was to investigate the effect of curcumin on regulating Notch signaling and provide basic data for using curcumin in prostate cancer therapy. METHODS: Notch pathway signal related proteins Notch 1, Jagged-1 and NICD were detected using Western blotting and RT-PCR. The proliferation and apoptosis were determined by MTT method and Elisa kits after curcumin treatment, respectively. Dual-Luciferase Reporter Assay was carried out to confirm that curcumin could target Notching signaling. In order to study whether Notch 1 expression could be downregulated by curcumin, Notch 1 siRNA and Notch 1 plasmid were used in Notch 1 down-regulation and over-expression. The effects of curcumin on cell cycle distribution and apoptosis related proteins expression were analyzed by flow cytometry and western blotting, separately. RESULTS: We found that Notch 1 signaling was down regulated in Notch 1 siRNA or Notch 1 plasmid transfected 145 cells after curcumin treatment. Curcumin induced G0/G1 arrest in DU-145 cells, and G0/G1 phase related regulatory factors Cyclin D1 and CDK2 expressions were inhibited. Meanwhile, p21 and p27 were up regulated. The apoptosis related protein p53 expression was increased, and apoptosis suppressor Bcl-2 was inhibited in DU-145 after curcumin treatment. Additionally, Caspase-3 and Caspase-9 were activated by curcumin. CONCLUSION: Curcumin induced apoptosis and G0/G1 arrest in DU-145 cells by down regulating Notch signaling. PMID- 27657826 TI - Anti-inflammatory activities of fenoterol through beta-arrestin-2 and inhibition of AMPK and NF-kappaB activation in AICAR-induced THP-1 cells. AB - The AMP-activated protein kinase (AMPK) pathway has been shown to be able to regulate inflammation in several cell lines. We reported that fenoterol, a beta2 adrenergic receptor (beta2-AR) agonist, inhibited lipopolysaccharide (LPS) induced AMPK activation and inflammatory cytokine production in THP-1 cells, a monocytic cell line in previous studies. 5-amino-1-beta-d-ribofuranosyl-imidazole 4-carboxamide (AICAR) is an agonist of AMPK. Whether AICAR induced AMPK activation and inflammatory cytokine production in THP-1 cells can be inhibited by fenoterol is unknown. In this study, we explored the mechanism of beta2-AR stimulation with fenoterol in AICAR-induced inflammatory cytokine secretion in THP-1 cells. We studied AMPK activation using p-AMPK and AMPK antibodies, nuclear factor-kappa B (NF-kappaB) activation and inflammatory cytokine secretion in THP 1 cells stimulated by beta2-AR in the presence or absence of AICAR and small interfering RNA (siRNA)-mediated knockdown of beta-arrestin-2 or AMPKalpha1 subunit. AICAR-induced AMPK activation, NF-kappaB activation and tumor necrosis factor (TNF)-alpha release were reduced by fenoterol. In addition, siRNA-mediated knockdown of beta-arrestin-2 abolished fenoterol's inhibition of AICAR-induced AMPK activation and TNF-alpha release, thus beta-arrestin-2 mediated the anti inflammatory effects of fenoterol in AICAR-treated THP-1 cells. Furthermore, siRNA-mediated knockdown of AMPKalpha1 significantly attenuated AICAR-induced NF kappaB activation and TNF-alpha release, so AMPKalpha1 was a key signaling molecule involved in AICAR-induced inflammatory cytokine production. These data suggested that fenoterol inhibited AICAR-induced AMPK activation and TNF-alpha release through beta-arrestin-2 in THP-1 cells. Management especially inhibition of AMPK signaling may provide new approaches and strategies for the treatments of immune diseases including inflammatory diseases and other critical illness. PMID- 27657827 TI - BACH1 silencing by siRNA inhibits migration of HT-29 colon cancer cells through reduction of metastasis-related genes. AB - BACKGROUND: Metastasis to distant organs is a hallmark of many tumor cells. BACH1 (BTB and CNC homology 1) is a transcriptional factor which promotes the migration and invasion of breast cancer cells. BACH1 expression and its target genes are intimately associated with the metastasis possibility of clinical samples, and BACH1 reduction leads to meaningful depletion in metastasis. The evaluation of BACH1 role in colon cancer remains elusive. This study seeks to further investigate the role of BACH1 in colon cancer cells. METHODS: Quantitative RT-PCR (qRT-PCR) was used to detect BACH1 expression and other related metastatic genes following siRNA knockdown in colon cancer HT-29 cells. And the protein level assessed by Western blot. MTT assay was to measure the changed cell viability after BACH1 siRNA transfection. Scratch-wound motility assays measured capacity of tumor cell migration of HT-29 cells after BACH1 silencing. RESULTS: The inhibitory effect of BACH1 was performed by siRNA knockdown using highly metastatic HT-29 colon cell lines. Quantitative RT-PCR and Western blot analysis revealed that the expression levels of BACH1 mRNA and protein in HT29 cells were significantly suppressed after transfection. Conversely, the BACH1 expression increased migration. Also the CXCR4 and MMP1 expression levels decreased following BACH1 knockdown in HT-29 cells. CONCLUSION: Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment. PMID- 27657829 TI - Chlorogenic acid a dietary polyphenol attenuates isoproterenol induced myocardial oxidative stress in rat myocardium: An in vivo study. AB - Intent of the present study has been made to appraise the cardioprotective effect of chlorogenic acid (CGA) on isoproterenol (ISO) induced myocardial infarction (MI) in male albino Wistar rats. ISO-induced myocardial damage was indicated by the elevated levels of marker enzymes such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LHPs) were significantly increased in the plasma and heart tissue. Activities of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the non enzymic antioxidants like vitamin C, vitamin E and reduced glutathione (GSH) were decreased in the erythrocytes, plasma and heart tissue of the ISO induced rats and myocardium infarct size as observed by staining with triphenyltetrazolium chloride (TTC). Histopathological observation corroborated with the bioochemical parameters. Oral administration of CGA at different doses (10, 20, 40mg/kg BW) for 19days prevented the above changes. The 40mg/kg BW of CGA was more pronounced than other two doses and brought back all the above parameters to near normalcy. PMID- 27657828 TI - Identification of novel VP35 inhibitors: Virtual screening driven new scaffolds. AB - Ebola virus is a single-stranded, negative-sense RNA virus that causes acute and serious life-threatening illness. In recent years the Ebola virus has spread through several countries in Africa, highlighting the need to develop new treatments for this disease and boosting a new research effort on this subject. However, so far there is no valid treatment for disease created by this pathogen. The Ebola virus Viral Protein 35 (VP35) is a multifunctional protein which is critical for virus replication and infection, and it is considered as a future target for drug development. In this study, we collected 144 VP35 inhibitors which shared the same core scaffold, and a common feature pharmacophore model HypoA was built based on inhibitor-receptor complexes. All 141 compounds were aligned based on the common feature pharmacophore model HypoA (three compounds could not map onto HypoA). The pharmacophore model HypoA was further optimized according to the actual interactions between inhibitors and VP35 protein, resulting in a new pharmacophore model HypoB which was applied for virtual screening. A 3D QSAR model was established by applying the 141 aligned compounds. For the training set, the 3D QSAR model gave a correlation coefficient r2 of 0.897, for the test set, the correlation coefficient r2 was 0.757. Then a virtual screening was carried out, which comprehensively employing the common feature pharmacophore model, 3D QSAR model and docking study, their combination in a hybrid protocol could help to mutually compensate for their limitations and capitalized on their mutual strengths. After the above three virtual screening methods orderly filtering, seven potential inhibitors with novel scaffolds were identified as new VP35 inhibitors. The mapping results of hit compounds onto pharmacophore model and 3D QSAR model, and the molecular interactions of the potential inhibitors with the active site residues have been discussed in detail. PMID- 27657830 TI - Preventive effect of Caralluma fimbriata vs. Metformin against high-fat diet induced alterations in lipid metabolism in Wistar rats. AB - The objective of the present study was to investigate the preventive effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) and Metformin (Met) against high-fat diet (HF-diet) induced alterations in lipid metabolism in Wistar rats. The experimental animals were divided into five groups, two of which were fed with chow diet and the other three with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of chow-fed rats, HF-fed rats and Met (20mg/kg body weight/day) to one of the HF-diet fed groups. At the end of 90days of experimental period, hypercholestermia, hypertriglycerdemia, with decreased HDL-cholesterol and increased LDL, VLDL cholesterol and atherogenic index and elevated levels of serum and hepatic transaminases and hepatic lipids (p<0.05) and alterations in the activities of enzymes of lipid metabolism, and the liver showed mild to severe distortion of the normal architecture as well as prominence and widening of the liver sinusoids as observed in HF-fed rats, were prevented by CFE/Met treatment. The results showed that CFE/Met supplementation ameliorated significantly the disturbance in serum and hepatic transaminases, plasma and hepatic lipid profile and lipid metabolism under HF-fed conditions. It can be concluded from these results that CFE might be valuable in reducing the alterations related to lipid metabolism under high calorie diet consumption. PMID- 27657831 TI - Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia. AB - Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (delta-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of delta-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and delta-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and delta-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with preeclampsia compared to healthy pregnant women, which may be related to the complications of this disease. PMID- 27657832 TI - Prevalence, determinants and genetic diversity of hepatitis C virus in the multi ethnic population living in Suriname. AB - Little is known about the epidemiology of HCV in Suriname, a former Dutch colony in South America. To study the prevalence, determinants and genetic diversity of HCV, a one-month survey was conducted at the only Emergency Department in the capital Paramaribo. Participants (>=18 years) completed an interviewer-led standardized HCV risk-factor questionnaire, were tested for HCV-antibodies, and if positive also for HCV RNA. The overall HCV prevalence was 1.0% (22/2128 participants; 95%CI 0.7-1.5). Male sex (OR=4.11; 95%CI 1.30-13.01), older age (OR=1.06 per year increase; 95%CI 1.04-1.09), Javanese ethnicity (OR=7.84; 95%CI 3.25-18.89) and cosmetic tattooing (OR=31.7; 95%CI 3.25-323.87) were independently associated with HCV-infection. Phylogenetic analysis revealed six distinct HCV subtypes, all HCV-genotype 2 (HCV-2): subtype 2f (also circulating in Indonesia) plus five yet unassigned HCV-2 subtypes exclusively linked to Suriname. PMID- 27657833 TI - Mood stabilizers inhibit cytomegalovirus infection. AB - Cytomegalovirus (CMV) infection can generate debilitating disease in immunocompromised individuals and neonates. It is also the most common infectious cause of congenital birth defects in infected fetuses. Available anti-CMV drugs are partially effective but are limited by some toxicity, potential viral resistance, and are not recommended for fetal exposure. Valproate, valpromide, and valnoctamide have been used for many years to treat epilepsy and mood disorders. We report for the first time that, in contrast to the virus-enhancing actions of valproate, structurally related valpromide and valnoctamide evoke a substantial and specific inhibition of mouse and human CMV in vitro. In vivo, both drugs safely attenuate mouse CMV, improving survival, body weight, and developmental maturation of infected newborns. The compounds appear to act by a novel mechanism that interferes with CMV attachment to the cell. Our work provides a novel potential direction for CMV therapeutics through repositioning of agents already approved for use in psychiatric disorders. PMID- 27657835 TI - Establishment of different plasmid only-based reverse genetics systems for the recovery of African horse sickness virus. AB - In an effort to simplify and expand the utility of African horse sickness virus (AHSV) reverse genetics, different plasmid-based reverse genetics systems were developed. Plasmids containing cDNAs corresponding to each of the full-length double-stranded RNA genome segments of AHSV-4 under control of a T7 RNA polymerase promoter were co-transfected in cells expressing T7 RNA polymerase, and infectious AHSV-4 was recovered. This reverse genetics system was improved by reducing the required plasmids from 10 to five and resulted in enhanced virus recovery. Subsequently, a T7 RNA polymerase expression cassette was incorporated into one of the AHSV-4 rescue plasmids. This modified 5-plasmid set enabled virus recovery in BSR or L929 cells, thus offering the possibility to generate AHSV-4 in any cell line. Moreover, mutant and cross-serotype reassortant viruses were recovered. These plasmid DNA-based reverse genetics systems thus offer new possibilities for investigating AHSV biology and development of designer AHSV vaccine strains. PMID- 27657836 TI - Novel antifouling nano-enhanced thin-film composite membrane containing cross linkable acrylate-alumoxane nanoparticles for water softening. AB - A novel thin-film composite (TFC) nanofiltration membrane was prepared using polymerization of pyrrole monomers on the PES ultrafiltration membrane. To improve the characteristics of hydrophobic polypyrrole (PPy) thin-film layer, cross-linkable acrylate-functionalized alumoxane nanoparticles with different concentrations were embedded into the thin-film during polymerization process, and thin-film nanocomposite (TFNC) membranes were prepared. The characteristics and performance of TFC and TFNC membranes were assessed through the morphological analyses (SEM, AFM), measurement of hydrophilicity and solid-liquid interfacial free energy, water permeability and Mg2+ removal tests. Addition of proper amount of nanoparticles into the polymerization mixture led to the preparation of membranes with more hydrophilic, thinner and smoother active layer as well as higher water permeability compared to TFC control membrane. TFNC membrane prepared with 0.025g of nanoparticles was the most efficient membrane since it exhibited the highest rejection of MgCl2 and MgSO4 salts. Antifouling capability of membranes, in terms of flux recovery and fouling parameters, demonstrated the high tolerance of TFNC against fouling. PMID- 27657834 TI - Endogenous retroviruses mobilized during friend murine leukemia virus infection. AB - We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. PMID- 27657837 TI - A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability. AB - BACKGROUND: Nanosuspension is one of the most promising strategies to improve the oral bioavailability of insoluble drugs. The existing techniques applied to produce nanosuspensions are classified as "bottom-up" or "top-down" methods, or a combination of both. Curcumin (CUR), a Biopharmaceutics Classification System (BCS) class IV substance, is a promising drug candidate in view of its good bioactivity, but its use is limited due to its poor solubility and permeability. In the present study, CUR nanosuspensions were developed to enhance CUR oral bioavailability using a cost-effective method different from conventional techniques. RESULTS: The physicochemical properties of CUR nanosuspensions were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The crystalline state of CUR in different nanosuspensions analyzed using differential scanning calorimeter (DSC) and X-ray diffraction analysis (PXRD) confirmed its amorphous state. In vitro dissolution degree of the prepared CUR nanosuspensions using TPGS or Brij78 as stabilizer was greatly increased. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 3.18 and 3.7 times after administration of CUR/TPGS nanosuspensions or CUR/Brij78 nanosuspensions, when compared with the administration of CUR suspension. CONCLUSIONS: CUR nanosuspensions produced by our cost-effective method could improve its oral bioavailability. In addition, the low-cost and time-saving method reported here is highly suitable for a fast and inexpensive preparation. PMID- 27657838 TI - Cervical cancer screening: How do we make sense of it all and what is the right balance? PMID- 27657839 TI - Exonuclease III-assisted cascade signal amplification strategy for label-free and ultrasensitive electrochemical detection of nucleic acids. AB - In this work, a simple, signal-on and label-free electrochemical biosensor for ultrasensitive DNA detection is reported on the basis of an autocatalytic and exonuclease III (Exo III)-assisted cascade signal amplification strategy. In the presence of target DNA (T-DNA), the hybridization between the 3'-protruding DNA fragment of hairpin DNA probe (HP1) and T-DNA triggered the Exo III cleavage process, accompanied by the releasing of T-DNA and autonomous generation of new DNA fragment which was used for the successive hybridization with the another hairpin DNA (HP2) on the electrode. After the Exo III cleavage process, numerous quadruplex-forming oligomers which caged in HP2 were liberated on the electrode surface and folded into G-quadruplex-hemin complexes with the help of K+ and hemin to give a remarkable electrochemical response. As a result, a low detection limit of 4.83fM with an excellent selectivity toward T-DNA was achieved. The developed electrochemical biosensor should be further extended for the detection of a wide spectrum of analytes and has great potential for the development of ultrasensitive biosensing platform for early diagnosis in gene-related diseases. PMID- 27657840 TI - An electrochemical lipopolysaccharide sensor based on an immobilized Toll-Like Receptor-4. AB - Infections affect millions of people each year and yet methods to ascertain their cause can take more than 24h to be effective. This delay between the presentation with symptoms and the ability to make an informed decision about treatment can have adverse consequences, including death in severe cases. Additionally, pathogen identification is a concern for public safety amid the growing threat of bioterrorism. Developing a detection system based on the immune system offers the advantage of broad specificity, while still remaining pertinent to human health. In this work, human Toll-Like Receptor-4 (TLR-4), a protein responsible for detecting lipopolysaccharide (LPS) of Gram-negative bacteria, was immobilized on both a large area and micro gold electrode via the tethering interaction of a modified Self-Assembled Monolayer (mSAM). In response to varying concentrations of its target, the protein-electrode combination showed a logarithmically proportional increased resistance to charge transfer from a solution-based redox probe, due to the formation of TLR-4 protein dimers. It also demonstrated excellent sensitivity to trace levels of Gram-negative bacteria, while remaining insensitive to both Gram-positive and viral challenges. Further characterization of our mSAM revealed that maintaining the appropriate receptor orientation on the electrode surface, mimicking TLR-4's role in a cellular context, was essential in producing a responsive sensor. PMID- 27657841 TI - An ultrasensitive electrochemiluminescence biosensor for the detection of concanavalin A based on Au nanoparticles-thiosemicarbazide functionalized PtNi nanocubes as signal enhancer. AB - A sandwich-configuration electrochemiluminescence (ECL) biosensor was constructed for detecting concanavalin A (ConA) based on peroxydisulfate/oxygen (S2O82-/O2) system. In this work, the gold nanoflower modified Zn-doped SnO2 was used as a substrate to adsorb recognition element horseradish peroxidase (HRP) for binding ConA. Then, Au nanoparticles-thiosemicarbazide functionalized PtNi nanocubes (AuNPs-TSC-PtNi NCs), as a novel ECL signal tracer, were incubated onto the electrode through a specific carbohydrate-ConA interaction, thus achieving a sandwiched structure. The integration of amplifying effect of both TSC and PtNi NCs on the ECL of S2O82-/O2 system endowed the biosensor a high sensitivity. The linear range for ConA detection was from 0.0010ng/mL to 10ng/mL with a detection limit of 0.0002ng/mL (S/N=3). PMID- 27657842 TI - Whole cell based microcontact imprinted capacitive biosensor for the detection of Escherichia coli. AB - In this study, a label-free, selective and sensitive microcontact imprinted capacitive biosensor was developed for the detection of Escherichia coli. The recognition of E. coli was successfully performed by this sensor prepared with the combination of microcontact imprinting method and capacitive biosensor technology. After preparation of bacterial stamps, microcontact-E. coli imprinted gold electrodes were generated using an amino acid based recognition element, N methacryloyl-L-histidine methylester (MAH), 2-Hydroxyethyl methacrylate (HEMA) as monomers and ethyleneglycol dimethacrylate (EGDMA) as crosslinker under UV polymerization. Real-time E. coli detection experiments were carried out within the range of 1.0*102-1.0*107CFU/mL. The unique combination of these two techniques provides selective detection with a detection limit of 70CFU/mL. The designed capacitive sensor has high selectivity and was able to distinguish E. coli when present together with competing bacterial strains which are known to have similar shape. In addition, the prepared sensor has the ability to detect E. coli with a recovery of 81-97% in e.g. river water. PMID- 27657843 TI - Rapid and ultrasensitive detection of active thrombin based on the Vmh2 hydrophobin fused to a Green Fluorescent Protein. AB - A fusion protein designed in order to combine the fluorescence emission of the Green Fluorescent Protein (GFP) with the adhesion ability of the class I hydrophobin Vmh2 was heterologously produced in the yeast Pichia pastoris. The Vmh2-GFP fusion protein has proven to be a smart and effective tool for the study of Vmh2 self-assembling. Since the two proteins were linked by the specific cutting site of the thrombin, the fusion protein was used as the active biological element in the realization of a thrombin biosensor. When the thrombin present in the target solution specifically hydrolyzed its cleavage sequence, a consequent decrease in the fluorescence intensity of the sample could be observed. The Vmh2-GFP based assay allowed quantification of thrombin in solution with a detection limit of 2.27aM. The specificity of the assay with respect to other proteases and proteins granted the measurement of thrombin added to healthy human plasma with same high sensitivity and a limit of detection of 2.3aM. Further advantages of the developed biosensor are the simplicity of its design and preparation, and the low requirements in terms of samples, reagents and time. PMID- 27657844 TI - A point-of-use microfluidic device with integrated photodetector array for immunoassay multiplexing: Detection of a panel of mycotoxins in multiple samples. AB - For a point-of-use analytical device to be successful in real-world applications, it needs to be rapid, simple to operate and, ideally, able to multiplex the detection of several analytes and samples. Mycotoxin detection in food and feedstock in particular has become increasingly relevant as these toxins, such as ochratoxin A (OTA), aflatoxin B1 (AFB1) and deoxynivalenol (DON), are subject to strict regulations and recommendations in the European Union. A novel, simple, negative pressure-driven device with manually operated magnetic valves was developed and the simultaneous immunodetection of these three mycotoxins was demonstrated via the laminar flow patterning of probes in an area of ~0.12mm2 and subsequent chemiluminescence generation via HRP-labeled antibodies. The three mycotoxins were detected in less than 20min at concentrations of 100ng/mL for OTA and DON and 3ng/mL for AFB1, spiked in a sample under analysis and simultaneously compared to a toxin-free reference and a standard contaminated with critical target concentrations. The on-chip optical detection was performed in a single acquisition step by integrating a microfabricated array of 25*25um2 hydrogenated amorphous silicon (a-Si:H) photosensors below the microfluidic chip. The device presented in this work is simple and effective for point-of-use multiplexing of immunoassays and was applied in this work to the screening of mycotoxins. PMID- 27657846 TI - Direct quantitative screening of influenza A virus without DNA amplification by single-particle dual-mode total internal reflection scattering. AB - Quantitative screening of influenza A (H7N9) virus without DNA amplification was performed based on single-particle dual-mode total internal reflection scattering (SD-TIRS) with a transmission grating (TG). A gold nanopad was utilized as a substrate for the hybridization of probe DNA molecules with the TIRS nanotag (silver-nanoparticle). The TG effectively isolated the scattering signals in first-order spectral images (n=+1) of the nanotag from that of the substrate, providing excellent enhancement of signal-to-noise and selectivity. By using single-DNA molecule/TIRS nanotag hybridization, target DNA molecules of H7N9 were detected down to 74 zM, which is at least 100,000 times lower than the current detection limit of 9.4fM. By simply modifying the design of the probe DNA molecules, this technique can be used to directly screen other viral DNAs in various human biological samples at the single-molecule level without target amplification. PMID- 27657845 TI - Fabrication of mediator-free hybrid nano-interfaced electrochemical biosensor for monitoring cancer cell proliferation. AB - Glucose, a chief energy source in cellular metabolism, has a significant role in cell proliferation. Cancer cells utilize more glucose than normal cells to meet the energy demand arising due to their uncontrolled proliferation. The present work reports the development of a nano-interfaced amperometric biosensor for rapid and accurate monitoring of glucose utilization by cancer cells. A hybrid nano-interface comprising a blend of carbon nanotubes (CNTs) and graphene (GR) was employed to enhance the surface area of the working electrode and favour direct electron transfer. Glucose oxidase (GOx) immobilized on the interface serves as the sensing element due to its high selectivity and sensitivity towards glucose. Utilization of glucose was monitored at pre-determined time intervals in MiaPaCa-2 cancer cells. The results obtained from the amperometric technique were compared with the values obtained from a commercial glucometer. Alamar blue assay was performed to check the proliferation rate of the cells. A good correlation was obtained between the proliferation rate and glucose utilization. The designed biosensor was found to be unaffected by the presence of potential interferents and hence may serve as a novel in vitro tool to rapidly quantify the proliferation rates of cancer cells in response to different treatment strategies. PMID- 27657847 TI - Thiamine biosensor based on oxidative trapping of enzyme-substrate intermediate. AB - In the present work, we describe a new thiamine amperometric biosensor based on thiamine pyrophosphate (ThDP)-dependent transketolase (TK)-catalyzed reaction, followed by the oxidative trapping of TK intermediate alpha,beta dihydroxyethylthiamine diphosphate (DHEThDP) within the enzymatic active site. For the biosensor design purpose, TK from Escherichia coli (TKec) was immobilized in Mg2Al-NO3 Layered Double Hydroxides (LDH) and the electrochemical detection was achieved with the TKec/LDH modified glassy carbon electrode (GCE). The transduction process was based on the ability of Fe(CN)63- to oxidize DHEThDP to glycolic acid along with ThDP regeneration. The released Fe(CN)64- was re oxidized at +0.5V vs Ag-AgCl and the reaction was followed by chronoamperometry. The TKec/LDH/GCE biosensor was optimized using the best TK donor substrates, namely l-erythrulose and d-fructose-6-phosphate. ThDP was assayed with great sensitivity (3831mAM-1cm-2) over 20-400nM linear range. PMID- 27657848 TI - Synthesis of adenosine-imprinted microspheres for the recognition of ADP ribosylated proteins. AB - Core-shell structural adenosine-imprinted microspheres were prepared via a two step procedure. Polystyrene core particles (CP) were firstly prepared via a reversible addition-fragmentation chain transfer (RAFT) polymerization leaving the iniferter on the surface of the cores, then a molecularly imprinted polymer (MIP) shell was synthesized on the surface of the cores by using acrylamide (AAm) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross linker. The formation and growth of the MIP layer were seen dependent on the initiator (AIBN), AAm and the polymerization time used within the polymerization. SEM/TEM images showed that the dimensions of the cores and shells were 2MUM and 44nm, respectively. The MIP microspheres exhibited a fast rebinding rate within 2h and a maximum adsorption capacity of 177MUg per gram for adenosine. The adsorption fitted a Langmuir-Freundlich (LF) isotherm model with a KLF value of 41mL/MUg and a qm value of 177MUg/g for the MIP microspheres. The values were larger than those for a non-molecularly imprinted polymer (NIP) particles (5mL/MUg and 88MUg/g) indicating a better adsorption ability towards adenosine. The MIP microspheres showed a good selectivity for adenosine with a higher adsorption (683nmol/g) for adenosine than that (91nmol/g, 24nmol/g and 54nmol/g) for guanosine, cytidine and uridine respectively. Further experiment proved that the adenosine-imprinted polymer microspheres also had a good selectivity for ADP ribosylated proteins that the MIP could extract the ADP-ribosylated proteins from the cell extract samples. PMID- 27657849 TI - Multiplexed instrument-free meningitis diagnosis on a polymer/paper hybrid microfluidic biochip. AB - Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Haemophilus influenzae type b (Hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. Because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. Herein, we report a polymer/paper hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) for multiplexed instrument-free diagnosis of these three major types of bacterial meningitis, with high sensitivity and specificity. Results can be visually observed by the naked eye or imaged by a smartphone camera under a portable UV light source. Without using any specialized laboratory instrument, the limits of detection of a few DNA copies per LAMP zone for N. meningitidis, S. pneumoniae and Hib were achieved within 1h. In addition, these three types of microorganisms spiked in artificial cerebrospinal fluid (ACSF) were directly detected simultaneously, avoiding cumbersome sample preparation procedures in conventional methods. Compared with the paper-free non-hybrid microfluidic biochip over a period of three months, the hybrid microfluidic biochip was found to have a much longer shelf life. Hence, this rapid, instrument-free and highly sensitive microfluidic approach has great potential for point-of-care (POC) diagnosis of multiple infectious diseases simultaneously, especially in resource limited settings. PMID- 27657850 TI - Automated Proposition Density Analysis for Discourse in Aphasia. AB - Purpose: This study evaluates how proposition density can differentiate between persons with aphasia (PWA) and individuals in a control group, as well as among subtypes of aphasia, on the basis of procedural discourse and personal narratives collected from large samples of participants. Method: Participants were 195 PWA and 168 individuals in a control group from the AphasiaBank database. PWA represented 6 aphasia types on the basis of the Western Aphasia Battery-Revised (Kertesz, 2006). Narrative samples were stroke stories for PWA and illness or injury stories for individuals in the control group. Procedural samples were from the peanut-butter-and-jelly-sandwich task. Language samples were transcribed using Codes for the Human Analysis of Transcripts (MacWhinney, 2000) and analyzed using Computerized Language Analysis (MacWhinney, 2000), which automatically computes proposition density (PD) using rules developed for automatic PD measurement by the Computerized Propositional Idea Density Rater program (Brown, Snodgrass, & Covington, 2007; Covington, 2007). Results: Participants in the control group scored significantly higher than PWA on both tasks. PD scores were significantly different among the aphasia types for both tasks. Pairwise comparisons for both discourse tasks revealed that PD scores for the Broca's group were significantly lower than those for all groups except Transcortical Motor. No significant quadratic or linear association between PD and severity was found. Conclusion: Proposition density is differentially sensitive to aphasia type and most clearly differentiates individuals with Broca's aphasia from the other groups. PMID- 27657851 TI - Application of Freeze-Dried Powders of Genetically Engineered Microbial Strains as Adsorbents for Rare Earth Metal Ions. AB - The adsorption behaviors of the rare earth metal ions onto freeze-dried powders of genetically engineered microbial strains were compared. Cell powders obtained from four kinds of strains, Bacillus subtilis 168 wild type (WT), lipoteichoic acid-defective (DeltaLTA), wall teichoic acid-defective (DeltaWTA), and cell wall hydrolases-defective (EFKYOJLp) strains, were used as an adsorbent of the rare earth metal ions at pH 3. The adsorption ability of the rare earth metal ions was in the order of EFKYOJLp > WT > DeltaLTA > DeltaWTA. The order was the same as the order of the phosphorus quantity of the strains. This result indicates that the main adsorption sites for the ions are the phosphate groups and the teichoic acids, LTA and WTA, that contribute to the adsorption of the rare earth metal ions onto the cell walls. The contribution of WTA was clearly greater than that of LTA. Each microbial powder was added to a solution containing 16 kinds of rare earth metal ions, and the removals (%) of each rare earth metal ion were obtained. The scandium ion showed the highest removal (%), while that of the lanthanum ion was the lowest for all the microbial powders. Differences in the distribution coefficients between the kinds of lanthanide ions by the EFKYOJLp and DeltaWTA powders were greater than those of the other strains. Therefore, the EFKYOJLp and DeltaWTA powders could be applicable for the selective extraction of the lanthanide ions. The DeltaLTA powder coagulated by mixing with a rare earth metal ion, although no sedimentation of the WT or DeltaWTA powder with a rare earth metal ion was observed under the same conditions. The EFKYOJLp powder was also coagulated, but its flocculating activity was lower than that of DeltaLTA. The DeltaLTA and EFKYOJLp powders have a long shape compared to those of the WT or DeltaWTA strain. The shapes of the cells will play an important role in the sedimentation of the microbial powders with rare earth metal ions. As the results, three kinds of the genetically engineered microbial powders revealed unique adsorption behaviors of the rare earth metal ions. PMID- 27657852 TI - Substrate-Induced Nanoscale Undulations of Borophene on Silver. AB - Two-dimensional (2D) materials tend to be mechanically flexible yet planar, especially when adhered on metal substrates. Here, we show by first-principles calculations that periodic nanoscale one-dimensional undulations can be preferred in borophenes on concertedly reconstructed Ag(111). This "wavy" configuration is more stable than its planar form on flat Ag(111) due to anisotropic high bending flexibility of borophene that is also well described by a continuum model. Atomic scale ultrahigh vacuum scanning tunneling microscopy characterization of borophene grown on Ag(111) reveals such undulations, which agree with theory in terms of topography, wavelength, Moire pattern, and prevalence of vacancy defects. Although the lattice is coherent within a borophene island, the undulations nucleated from different sides of the island form a distinctive domain boundary when they are laterally misaligned. This structural model suggests that the transfer of undulated borophene onto an elastomeric substrate would allow for high levels of stretchability and compressibility with potential applications to emerging stretchable and foldable devices. PMID- 27657853 TI - Notes from the Field: Furanyl-Fentanyl Overdose Events Caused by Smoking Contaminated Crack Cocaine - British Columbia, Canada, July 15-18, 2016. AB - On July 15 2016, Surrey Memorial Hospital's emergency department notified the medical health officer on call of a sharp increase in opioid overdose events in Surrey, Fraser Health Authority, in British Columbia, Canada. During July 15-18, the number of persons with suspected opioid overdose evaluated in Surrey Memorial Hospital's emergency department increased approximately 170%, from an average of four suspected cases per day during the period January-June 2016 to 43 (nearly 11 per day) during the 4-day period (Figure). Most patients (22 [51%]) became unconscious after smoking what they believed to be crack cocaine. The majority of overdose events occurred within a small geographic area in Surrey that has a high population of homeless persons and persons who use illicit drugs, including opioids and crack cocaine. Most cases occurred in males (36 cases [84%]); the average age of the patients was 42 years (range = 18-63 years). Forty (93%) patients were brought to the emergency department by ambulance. A total of 37 (86%) patients received injectable naloxone before arriving in the emergency department, including 12 who received it only from community members, 16 who received it only from paramedics, five who received it from both community members and paramedics, one who received it from the fire department and paramedics, and one who received it from the fire department, community, and paramedics; for two patients, the source of naloxone was not known. Reports from first responders, the community, and emergency department staff members indicated that patients required high doses of injectable naloxone, in some cases up to 3.0 mg (usual dose = 0.4 mg). Thirty-five (81%) patients were treated and discharged within a few hours, two patients left without being seen by a health care provider, and six patients were admitted to the hospital; among these, three were transferred to the intensive care unit, one of whom died. PMID- 27657854 TI - Digenite Nanosheets Synthesized by Thermolysis of Layered Copper-Alkanethiolate Frameworks. AB - Copper sulfide nanocrystals support localized surface plasmon resonances in the near-infrared wavelengths and have significant potential as active plasmonic nanomaterials due to the tunability of this optical response. While numerous strategies exist for synthesizing copper sulfide nanocrystals, few methods result in nanocrystals with both controlled morphological shapes and crystallinity. Here, we synthesize and characterize ultrathin (<5 nm) Cu9S5 nanosheets that are formed by solventless thermolysis, utilizing Cu alkanethiolates as single-source precursors. Layered Cu alkanethiolate precursors adopt a highly ordered structure which can be further stabilized in the presence of Cl- and also serve to template the formation of nanosheets. We show that, in the absence of Cl-, only isotropic and disk-like Cu2-xS nanocrystals form. These findings offer further insight into the use of layered metal-organic single-source precursors as templates for anisotropic nanocrystal growth. PMID- 27657856 TI - When "Actionable" Genomic Sequencing Results Cannot Be Acted Upon. PMID- 27657857 TI - Effects of Koumine on Adjuvant- and Collagen-Induced Arthritis in Rats. AB - To examine the effect of koumine, a Gelsemium alkaloid, on two experimental models of rheumatoid arthritis (RA), rats with adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) were administered koumine (0.6, 3, or 15 mg/kg/day) or vehicle through gastric gavage (i.g.). Clinical evaluation was performed via measurements of hind paw volume, arthritis index (AI) score, mechanical withdrawal threshold, organ weight, and by radiographic and histological examinations. Levels of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and antitype II collagen (CII) antibody were also examined. In rats with AIA, koumine reduced the AI score and mechanical allodynia of the injected hind paw in a dose-dependent manner and significantly inhibited increase in thymus and liver weights. In rats with CIA, koumine inhibited increase in hind paw volume, AI score, and mechanical allodynia in a dose-dependent manner and reduced joint space narrowing. Furthermore, koumine also attenuated the increase in the expression of IL-1beta and TNF-alpha, as well as the robust increase of serum anti-CII antibodies in response to immunization. These results suggested that koumine effectively attenuated arthritis progression in two rat models of RA and that this therapeutic effect may be associated with its immunoregulatory action. PMID- 27657855 TI - Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration. AB - Importance: Age-related macular degeneration (AMD) is a multifactorial disease with genetic and environmental factors contributing to risk. Histopathologic changes underlying AMD are not fully understood, particularly the relationship between choriocapillaris (CC) dysfunction and phenotypic variability of this disease. Objective: To examine histopathologic changes in the CC of eyes with clinically documented AMD. Design, Setting, and Participants: The study was designed in 2011. Tissues were collected post mortem (2012-2016), and histopathological images were obtained from participants enrolled in AMD studies since 1988. Clinical records and images were collected from participants as standard protocol. Eyes without AMD (n = 4) and eyes with early (n = 9), intermediate (n = 5), and advanced stages of AMD (geographic atrophy, n = 5; neovascular disease, n = 13) were evaluated. Choroidal vasculature was labeled using Ulex europaeus agglutinin lectin and examined using confocal microscopy. Main Outcomes and Measures: A standardized classification system was applied to determine AMD stage. Ocular records and images were reviewed and histopathologic analyses performed. Viability of the choroidal vasculature was analyzed for each AMD stage. Results: All participants were white. Fourteen were male, and 16 were female. The mean age was 90.5 years among AMD patients and 88.5 years among control participants. Submacular CC dropout without retinal pigment eipthelial (RPE) loss was observed in all cases with early stages of AMD. Higher vascular area loss for each AMD stage was observed compared with control participants: 20.5% in early AMD (95% CI, 11.2%-40.2%; P < .001), 12.5% in intermediate AMD (95% CI, 2.9%-21.4%; P = .01), 39.0% loss in GA (95% CI, 32.1%-45.4%; P < .001), and 38.2% loss in neovascular disease where RPE remained intact (95% CI, 27.7% 47.9%; P < .001). Hypercellular, apparent neovascular buds were adjacent to areas of CC loss in 22.2% of eyes with early AMD and 40% of eyes with intermediate AMD. Conclusions and Relevance: Retinal pigment epithelial atrophy preceded CC loss in geographic atrophy, but CC loss occurred in the absence of RPE atrophy in 2 of 9 eyes with early-stage AMD. Given the cross-sectional nature of this study and the small number of eyes evaluated, definitive conclusions regarding this progression cannot be determined with certainty. We speculate that neovascular buds may be a precursor to neovascular disease. Hypoxic RPE resulting from reduced blood supply might upregulate production of vascular endothelial growth factor, providing the stimulus for neovascular disease. PMID- 27657859 TI - A brief history of water. PMID- 27657858 TI - Characterization and Risk Factor Analysis for Recurrence Following Microendoscopic Diskectomy for Lumbar Disk Herniation. AB - Background and Study Aims Microendoscopic diskectomy (MED) has become an established minimally invasive procedure in surgical treatment for lumbar disk herniation (LDH). LDH recurrence following surgery is also an important problem in MED because the risk of LDH recurrence may surpass the advantages of MED. The purpose of this study was to investigate the characteristics of recurrence following MED for LDH and identify the risk factors for a recurrence. Materials and Methods A total of 163 patients who underwent MED for LDH and could be followed for a minimum of 1 year after surgery were enrolled in this study (follow-up [FU] rate: 79.9%). We investigated the characteristics of LDH recurrence and conducted a comparative study between the patient groups with and without recurrence to identify the risk factors for the recurrence. Results The recurrence of LDH was observed in 19 patients (11.7%) during a mean of 38 months FU. Although the mean length of time from MED to recurrence was 19.2 months, 36.8% of the LDH recurrence occurred in the first 3 months following MED. Eleven patients were treated successfully by conservative treatments, and the remaining eight patients had to undergo revision surgery (MED in five patients, microdiskectomy in one, and instrumented fusion in two). In the analysis of risk factors for the recurrence, the presence of diabetes mellitus (DM) was significantly correlated with the recurrence (p = 0.0027). Conclusions The recurrence rate following MED for LDH was equivalent to those of previous reports of conventional and microscopic diskectomy. However, a third of the LDH recurrences occurred in the first 3 months after MED. We should pay attention to LDH recurrence at an early phase following MED and recognize the presence of DM as a risk factor for LDH recurrence. PMID- 27657860 TI - Synthesis: Click chemistry gets reversible. PMID- 27657862 TI - Heterogeneous catalysis: More than skimming the surface. PMID- 27657861 TI - Organic chemistry: A light touch breaks a strong ring. PMID- 27657863 TI - Organometallic chemistry: Taking ferrocenium up a notch. PMID- 27657864 TI - Homogeneous catalysis: Eight irons hit the right spin. PMID- 27657865 TI - Creating complex molecular topologies by configuring DNA four-way junctions. AB - The realization of complex topologies at the molecular level represents a grand challenge in chemistry. This necessitates the manipulation of molecular interactions with high precision. Here we show that single-stranded DNA (ssDNA) knots and links can be created by utilizing the inherent topological properties that pertain to the DNA four-way junction, at which the two helical strands form a node and can be configured conveniently and connected for complex topological construction. Using this strategy, we produced series of ssDNA topoisomers with the same sequences. By finely designing the curvature and torsion, double stranded DNA knots were accessed by hybridizing and ligating the complementary strands with the knotted ssDNA templates. Furthermore, we demonstrate the use of a constructed ssDNA knot both to probe the topological conversion catalysed by DNA topoisomerase and to study the DNA replication under topological constraint. PMID- 27657866 TI - Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication. AB - The non-enzymatic replication of RNA is thought to have been a critical process required for the origin of life. One unsolved difficulty with non-enzymatic RNA replication is that template-directed copying of RNA results in a double-stranded product. After strand separation, rapid strand reannealing outcompetes slow non enzymatic template copying, which renders multiple rounds of RNA replication impossible. Here we show that oligoarginine peptides slow the annealing of complementary oligoribonucleotides by up to several thousand-fold; however, short primers and activated monomers can still bind to template strands, and template directed primer extension can still occur, all within a phase-separated condensed state, or coacervate. Furthermore, we show that within this phase, partial template copying occurs even in the presence of full-length complementary strands. This method to enable further rounds of replication suggests one mechanism by which short non-coded peptides could have enhanced early cellular fitness, and potentially explains how longer coded peptides, that is, proteins, came to prominence in modern biology. PMID- 27657868 TI - In situ observation of self-assembled hydrocarbon Fischer-Tropsch products on a cobalt catalyst. AB - Fischer-Tropsch synthesis is a heterogeneous catalytic reaction that creates approximately 2% of the world's fuel. It involves the synthesis of linear hydrocarbon molecules from a gaseous mixture of carbon monoxide and hydrogen at high pressures (from a few to tens of bars) and high temperatures (200-350 degrees C). To gain further insight into the fundamental mechanisms of this industrial process, we have used a purpose-built scanning tunnelling microscope to monitor a cobalt model catalyst under reaction conditions. We show that, after 30 minutes of reaction, the terraces of the cobalt catalyst are covered by parallel arrays of stripes. We propose that the stripes are formed by the self assembly of linear hydrocarbon product molecules. Surprisingly, the width of the stripes corresponds to molecules that are 14 or 15 carbon atoms long. We introduce a simple model that explains the accumulation of such long molecules by describing their monomer-by-monomer synthesis and explicitly accounting for their thermal desorption. PMID- 27657867 TI - Dearomative dihydroxylation with arenophiles. AB - Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules-arenophiles-that results in their para cycloaddition with a variety of aromatic compounds. The approach uses N-N arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products. PMID- 27657869 TI - Force-induced tautomerization in a single molecule. AB - Heat transfer, electrical potential and light energy are common ways to activate chemical reactions. Applied force is another way, but dedicated studies for such a mechanical activation are limited, and this activation is poorly understood at the single-molecule level. Here, we report force-induced tautomerization in a single porphycene molecule on a Cu(110) surface at 5 K, which is studied by scanning probe microscopy and density functional theory calculations. Force spectroscopy quantifies the force needed to trigger tautomerization with submolecular spatial resolution. The calculations show how the reaction pathway and barrier of tautomerization are modified in the presence of a copper tip and reveal the atomistic origin of the process. Moreover, we demonstrate that a chemically inert tip whose apex is terminated by a xenon atom cannot induce the reaction because of a weak interaction with porphycene and a strong relaxation of xenon on the tip as contact to the molecule is formed. PMID- 27657871 TI - Directionally tunable and mechanically deformable ferroelectric crystals from rotating polar globular ionic molecules. AB - Ferroelectrics are used in a wide range of applications, including memory elements, capacitors and sensors. Recently, molecular ferroelectric crystals have attracted interest as viable alternatives to conventional ceramic ferroelectrics because of their solution processability and lack of toxicity. Here we show that a class of molecular compounds-known as plastic crystals-can exhibit ferroelectricity if the constituents are judiciously chosen from polar ionic molecules. The intrinsic features of plastic crystals, for example, the rotational motion of molecules and phase transitions with lattice-symmetry changes, provide the crystals with unique ferroelectric properties relative to those of conventional molecular crystals. This allows a flexible alteration of the polarization axis direction in a grown crystal by applying an electric field. Owing to the tunable nature of the crystal orientation, together with mechanical deformability, this type of molecular crystal represents an attractive functional material that could find use in a diverse range of applications. PMID- 27657870 TI - Engineering nanometre-scale coherence in soft matter. AB - Electronic delocalization in redox-active polymers may be disrupted by the heterogeneity of the environment that surrounds each monomer. When the differences in monomer redox-potential induced by the environment are small (as compared with the monomer-monomer electronic interactions), delocalization persists. Here we show that guanine (G) runs in double-stranded DNA support delocalization over 4-5 guanine bases. The weak interaction between delocalized G blocks on opposite DNA strands is known to support partially coherent long-range charge transport. The molecular-resolution model developed here finds that the coherence among these G blocks follows an even-odd orbital-symmetry rule and predicts that weakening the interaction between G blocks exaggerates the resistance oscillations. These findings indicate how sequence can be exploited to change the balance between coherent and incoherent transport. The predictions are tested and confirmed using break-junction experiments. Thus, tailored orbital symmetry and structural fluctuations may be used to produce coherent transport with a length scale of multiple nanometres in soft-matter assemblies, a length scale comparable to that of small proteins. PMID- 27657872 TI - The dipolar endofullerene HF@C60. AB - The cavity inside fullerenes provides a unique environment for the study of isolated atoms and molecules. We report the encapsulation of hydrogen fluoride inside C60 using molecular surgery to give the endohedral fullerene HF@C60. The key synthetic step is the closure of the open fullerene cage with the escape of HF minimized. The encapsulated HF molecule moves freely inside the cage and exhibits quantization of its translational and rotational degrees of freedom, as revealed by inelastic neutron scattering and infrared spectroscopy. The rotational and vibrational constants of the encapsulated HF molecules were found to be redshifted relative to free HF. The NMR spectra display a large (1)H-(19)F J coupling typical of an isolated species. The dipole moment of HF@C60 was estimated from the temperature dependence of the dielectric constant at cryogenic temperatures and showed that the cage shields around 75% of the HF dipole. PMID- 27657875 TI - Corrigendum: Self-assembled molecular p/n junctions for applications in dye sensitized solar energy conversion. PMID- 27657873 TI - Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells. AB - The controlled activation of proteins in living cells is an important goal in protein-design research, but to introduce an artificial activation switch into membrane proteins through rational design is a significant challenge because of the structural and functional complexity of such proteins. Here we report the allosteric activation of two types of membrane-bound neurotransmitter receptors, the ion-channel type and the G-protein-coupled glutamate receptors, using coordination chemistry in living cells. The high programmability of coordination chemistry enabled two His mutations, which act as an artificial allosteric site, to be semirationally incorporated in the vicinity of the ligand-binding pockets. Binding of Pd(2,2'-bipyridine) at the allosteric site enabled the active conformations of the glutamate receptors to be stabilized. Using this approach, we were able to activate selectively a mutant glutamate receptor in live neurons, which initiated a subsequent signal-transduction pathway. PMID- 27657876 TI - Brief encounters with dubnium. PMID- 27657877 TI - Thiol-Ene Modified Amorphous Carbon Substrates: Surface Patterning and Chemically Modified Electrode Preparation. AB - Amorphous carbon (aC) films are chemically stable under ambient conditions or when interfaced with aqueous solutions, making them a promising material for preparing biosensors and chemically modified electrodes. There are a number of wet chemical methods capable of tailoring the reactivity and wettability of aC films, but few of these chemistries are compatible with photopatterning. Here, we introduce a method to install thiol groups directly onto the surface of aC films. These terminal thiols are compatible with thiol-ene click reactions, which allowed us to rapidly functionalize and pattern the surface of the aC films. We thoroughly characterized the aC films and confirmed the installation of surface bound thiols does not significantly oxidize the surface or change its topography. We also determined the conditions needed to selectively attach alkene-containing molecules to these films and show the reaction is proceeding through a thiol mediated reaction. Lastly, we demonstrate the utility of our approach by photopatterning the aC films and preparing ferrocene-modified aC electrodes. The chemistry described here provides a rapid means of fabricating sensors and preparing photoaddressable arrays of (bio)molecules on stable carbon interfaces. PMID- 27657874 TI - Switchable photooxygenation catalysts that sense higher-order amyloid structures. AB - Proteins can misfold into amyloid structures that are associated with diseases; however, the same proteins often have important biological roles. To degrade selectively the amyloid form without affecting the fraction of functional protein is, therefore, an attractive goal. Here we report target-state-dependent photooxygenation catalysts that are active only when bound to the cross-beta sheet structure that is characteristic of pathogenic aggregated amyloid proteins. We show these catalysts can selectively oxygenate the amyloid form of amyloid beta-protein (Abeta) 1-42 in the presence of non-amyloid off-target substrates. Furthermore, photooxygenation with a catalyst that bears an Abeta-binding peptide attenuated the Abeta pathogenicity in the presence of cells. We also show that selective photooxygenation is generally applicable to other amyloidogenic proteins (amylin, insulin, beta2-microglobulin, transthyretin and alpha synuclein) and does not affect the physiologically functional non-aggregate states of these proteins. This is the first report of an artificial catalyst that can be selectively and reversibly turned on and off depending on the structure and aggregation state of the substrate protein. PMID- 27657878 TI - How do consumer leaders co-create value in mental health organisations? AB - Objectives Contemporary mental health policies call for consumers to be involved in decision-making processes within mental health organisations. Some organisations have embraced leadership roles for consumers, but research suggests consumers remain disempowered within mental health services. Drawing on a service dominant logic, which emphasises the co-creation of value of services, the present study provides an overview of consumer leadership within mental health organisations in the Australian Capital Territory. Methods Mental health organisations subscribing to the local peak body mailing list were invited to complete a survey about consumer leadership. Survey data were summarised using descriptive statistics and interpreted through the lens of service-dominant logic. Results Ways in which organisations may create opportunities for consumers to co-create value within their mental health services included soliciting feedback, involving consumer leaders in service design, having consumer leaders involved in hiring decisions and employing consumer leaders as staff or on boards. Strategies that organisations used to develop consumer leaders included induction, workshops and training in a variety of organisational processes and skills. Conclusions The findings of the present study extend the application of a service-dominant logic framework to consumer leadership within mental health organisations through consideration of the diverse opportunities that organisations can provide for consumer co-creation of service offerings. What is known about the topic? Policy calls for consumer involvement in all levels of mental health service planning, implementation and delivery. The extent to which service organisations have included consumer leaders varies, but research suggests that this inclusion can be tokenistic or that organisations choose to work with consumers who are less likely to challenge the status quo. Service literature has explored the way consumers can co-create value of their own health care, but is yet to explore consumers' co-creation of value at a systemic level. What does the paper add? This paper outlines ways in which mental health organisations report involving consumers in leadership positions, including having consumers on boards, having consumers on recruitment panels and providing leadership training for consumers. These initiatives are considered in terms of the potential value co-created within mental health services by consumers in leadership, suggesting that consumer leaders are a resource to mental health organisations in terms of the value brought to service offerings. What are the implications for practitioners? Research suggests that medical professionals have been resistant to increased consumer leadership within mental health services. The findings of the present study emphasise the value that can be brought to service organisations by consumer leaders, suggesting that mental health practitioners may reconsider their approach and attitudes towards consumer leadership in the sector. PMID- 27657879 TI - Dermatography (Medical Tattooing) for Scars and Skin Grafts in Head and Neck Patients to Improve Appearance and Quality of Life. AB - Importance: Dermatography (medical tattooing) is often overlooked as an adjuvant procedure to improve color mismatch in the head and neck area, and its effect on patient satisfaction and quality of life has not been evaluated, to our knowledge. Objective: To analyze the effect of dermatography on the subjective perception of the appearance of scars and skin grafts and the quality of life in head and neck patients. Design, Setting, and Participants: Case series of patients undergoing dermatography at the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, between July 1, 2007, and April 1, 2015. Participants were invited to respond to 2 questionnaires measuring their scar or graft appearance and their quality of life before and after dermatography as an adjuvant treatment for benign or malignant head and neck tumors. Intervention: Use of dermatography. Main Outcomes and Measures: Two questionnaires evaluating a visual analog scale score (range, 0-10) and multiple questions on a 5-point scale focusing on satisfaction with the appearance and the quality of life. Results: Among 76 patients, 56 (74%) were included in the study. The mean (SD) age of the study cohort was 56.5 (16.0) years, and 42 (75%) were female. The mean improvement in scar or skin graft perception on the visual analog scale of the modified Utrecht Questionnaire for Outcome Assessment in Aesthetic Rhinoplasty before and after dermatography was 4 points. On the modified Patient Scar Assessment Questionnaire, uniform improvement of approximately 1 point across 9 questions was observed. The answers to all patient satisfaction and quality-of life questions on both questionnaires improved significantly after dermatography. Conclusions and Relevance: Dermatography is an effectual adjuvant procedure to improve the subjective perception of scar and skin graft appearance and the quality of life in head and neck patients. Level of Evidence: 4. PMID- 27657880 TI - Flow-Tube Investigations of Hypergolic Reactions of a Dicyanamide Ionic Liquid Via Tunable Vacuum Ultraviolet Aerosol Mass Spectrometry. AB - The unusually high heats of vaporization of room-temperature ionic liquids (RTILs) complicate the utilization of thermal evaporation to study ionic liquid reactivity. Although effusion of RTILs into a reaction flow-tube or mass spectrometer is possible, competition between vaporization and thermal decomposition of the RTIL can greatly increase the complexity of the observed reaction products. In order to investigate the reaction kinetics of a hypergolic RTIL, 1-butyl-3-methylimidazolium dicyanamide (BMIM+DCA-) was aerosolized and reacted with gaseous nitric acid, and the products were monitored via tunable vacuum ultraviolet photoionization time-of-flight mass spectrometry at the Chemical Dynamics Beamline 9.0.2 at the Advanced Light Source. Reaction product formation at m/z 42, 43, 44, 67, 85, 126, and higher masses was observed as a function of HNO3 exposure. The identities of the product species were assigned to the masses on the basis of their ionization energies. The observed exposure profile of the m/z 67 signal suggests that the excess gaseous HNO3 initiates rapid reactions near the surface of the RTIL aerosol. Nonreactive molecular dynamics simulations support this observation, suggesting that diffusion within the particle may be a limiting step. The mechanism is consistent with previous reports that nitric acid forms protonated dicyanamide species in the first step of the reaction. PMID- 27657881 TI - Dynamic Computational Model of Symptomatic Bacteremia to Inform Bacterial Separation Treatment Requirements. AB - The rise of multi-drug resistance has decreased the effectiveness of antibiotics, which has led to increased mortality rates associated with symptomatic bacteremia, or bacterial sepsis. To combat decreasing antibiotic effectiveness, extracorporeal bacterial separation approaches have been proposed to capture and separate bacteria from blood. However, bacteremia is dynamic and involves host pathogen interactions across various anatomical sites. We developed a mathematical model that quantitatively describes the kinetics of pathogenesis and progression of symptomatic bacteremia under various conditions, including bacterial separation therapy, to better understand disease mechanisms and quantitatively assess the biological impact of bacterial separation therapy. Model validity was tested against experimental data from published studies. This is the first multi-compartment model of symptomatic bacteremia in mammals that includes extracorporeal bacterial separation and antibiotic treatment, separately and in combination. The addition of an extracorporeal bacterial separation circuit reduced the predicted time of total bacteria clearance from the blood of an immunocompromised rodent by 49%, compared to antibiotic treatment alone. Implementation of bacterial separation therapy resulted in predicted multi-drug resistant bacterial clearance from the blood of a human in 97% less time than antibiotic treatment alone. The model also proposes a quantitative correlation between time-dependent bacterial load among tissues and bacteremia severity, analogous to the well-known 'area under the curve' for characterization of drug efficacy. The engineering-based mathematical model developed may be useful for informing the design of extracorporeal bacterial separation devices. This work enables the quantitative identification of the characteristics required of an extracorporeal bacteria separation device to provide biological benefit. These devices will potentially decrease the bacterial load in blood. Additionally, the devices may achieve bacterial separation rates that allow consequent acceleration of bacterial clearance in other tissues, inhibiting the progression of symptomatic bacteremia, including multi-drug resistant variations. PMID- 27657882 TI - Disease Status and Pubertal Stage Predict Improved Growth in Antitumor Necrosis Factor Therapy for Pediatric Inflammatory Bowel Disease. AB - BACKGROUND: Growth failure is well-recognized in pediatric inflammatory bowel disease (PIBD; <18 years). We aimed to examine whether antitumor necrosis factor (TNF) therapy improves growth in a PIBD population-based cohort. METHODS: A retrospective review of all Scottish children receiving anti-TNF (infliximab [IFX] and adalimumab [ADA]) from 2000 to 2012 was performed; height was collected at 12 months before anti-TNF (T-12), start (T0), and 12 (T+12) months after anti TNF. RESULTS: Ninety-three of 201 treated with IFX and 28 of 49 with ADA had satisfactory growth data; 66 had full pubertal data. Univariate analysis demonstrated early pubertal stages (Tanner 1-3 n = 44 vs T4-5 n = 22), disease remission, disease duration >=2 years, and duration of IFX >=12 months were associated with improved linear growth for IFX; for ADA only improvement was seen in Tanner 1-3. For IFX, Tanner 1-3 median Delta standard deviation scores for height (Ht SDS) -0.3 (-0.7, 0.2) at T0 changed to 0.04 (-0.5, 0.7) at T+12 (P < 0.001) versus -0.01 (-0.5, 0.9) at T0 in T4-5 changed to -0.01 (-0.4, 0.2) at T+12 (P > 0.05). For IFX disease duration >=2 year, median Delta Ht SDS was -0.13 (-0.6, 0.3) at T0 then 0.07 (-0.3, 0.6) at T+12 (P < 0.001). Remission improved Delta Ht SDS (median Delta Ht SDS -0.14 [-0.6, 0.3] at T0 to 0.17 [-0.2, 0.7] at T+12 [P < 0.001]). Multiple regression analysis demonstrated corticosteroid usage at T0 predicted improved Delta Ht SDS at T+12 for IFX and ADA. CONCLUSIONS: Anti TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty with remission a key growth-promoting strategy in pediatric Crohn disease. PMID- 27657885 TI - Nuclear Magnetic Resonance Metabolomic Profiling of Mouse Kidney, Urine and Serum Following Renal Ischemia/Reperfusion Injury. AB - BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in (patho)physiological changes of integrated living systems. Here, we performed 1H-Nuclear Magnetic Resonance metabolomics using urine, serum and kidney samples from a mouse model of renal I/R. METHODS: Renal 30-min ischemia was induced in 12-week-old C57BL/6J male mice by bilaterally clamping vascular pedicles, and was followed by 6, 24 or 48-hour reperfusion (n = 12/group). Sham-operated mice were used as controls. Statistical discriminant analyses, i.e. principal component analysis and orthogonal projections to latent structures (OPLS-DA), were performed on urine, serum and kidney lysates at each time-point. Multivariate receiver operating characteristic (ROC) curves were drawn, and sensitivity and specificity were calculated from ROC confusion matrix (with averaged class probabilities across 100 cross validations). RESULTS: Urine OPLS-DA analysis showed a net separation between I/R and sham groups, with significant variations in levels of taurine, di- and tri methylamine, creatine and lactate. Such changes were observed as early as 6 hours post reperfusion. Major metabolome modifications occurred at 24h post reperfusion. At this time-point, correlation coefficients between urine spectra and conventional AKI biomarkers, i.e. serum creatinine and urea levels, reached 0.94 and 0.95, respectively. The area under ROC curve at 6h, 24h and 48h post surgery were 0.73, 0.98 and 0.97, respectively. Similar discriminations were found in kidney samples, with changes in levels of lactate, fatty acids, choline and taurine. By contrast, serum OPLS-DA analysis could not discriminate sham operated from I/R-exposed animals. CONCLUSIONS: Our study demonstrates that renal I/R in mouse causes early and sustained metabolomic changes in urine and kidney composition. The most implicated pathways at 6h and 24h post reperfusion include gluconeogenesis, taurine and hypotaurine metabolism, whereas protein biosynthesis, glycolysis, and galactose and arginine metabolism are key at 48h post reperfusion. PMID- 27657886 TI - Regulation of Rho GTPases from the lateral sides of migrating cells. AB - Migratory polarity and epithelial polarity share many common regulatory mechanisms. Rho GTPases play a key role in modulating cell polarity, which in migrating cells has been conventionally studied along the solitary front-rear axis. In recent work, we discovered that Prickle1 (Pk1), a core com-ponent of planar cell polarity (PCP) signaling, mediates a novel lateral signaling pathway that coordinates multi-axial protrusive activities from the lateral cortex of migrating cancer cells. We identified that Arhgap21 and 23 are essential effectors of Pk1, and that lateral signaling regulates RhoA, actomyosin and focal adhesion dynamics. Interestingly, we showed that lateral signaling coordinates shape dynamics that are critical during cell migration and function orthogonally to front-rear directional polarity. PMID- 27657887 TI - The Stigma of Suicide Survivorship and Related Consequences-A Systematic Review. AB - BACKGROUND: considerable proportion of the population experiences major life disruptions after losing a loved one to suicide. Social stigma attached to suicide survivors adds to complications occurring in the course of suicide bereavement. Despite its known risks, stigma related to suicide survivors has been sparsely investigated. METHODS: We conducted a systematic literature search in PubMed, Web of Science, PsycInfo and PsyArticles, of studies indexed up through August 2015. Articles were eligible for inclusion if they addressed experiences of stigma in suicide survivors, compared them to other bereavement populations, or investigated stigmatizing attitudes within the public. The search was restricted to English-language studies. RESULTS: 25 records matched inclusion criteria. Study designs were heterogeneous, making comparisons difficult. Results demonstrated that suicide survivors experience stigma in the form of shame, blame, and avoidance. Suicide survivors showed higher levels of stigma than natural death survivors. Stigma was linked to concealment of the death, social withdrawal, reduced psychological and somatic functioning, and grief difficulties. Only one study investigated stigmatizing attitudes towards suicide survivors among the general population. LIMITATIONS: Internal and external validity of the studies was restricted by a lack of valid measures and selection bias. CONCLUSIONS: More methodologically sound research is needed to understand the impact of stigma on suicide survivors' grief trajectories and to separate it from other grief aspects. Clinicians and grief-counselors as well as the public should be educated about the persistent stigma experienced by suicide survivors. PMID- 27657888 TI - Drivers' Visual Characteristics when Merging onto or Exiting an Urban Expressway. AB - The aim of this study is to examine drivers' visual and driving behavior while merging onto or exiting an urban expressway with low and high traffic densities. The analysis was conducted according to three periods (approaching, merging or exiting, and accelerating or decelerating). A total of 10 subjects (8 males and 2 females) with ages ranging from 25 to 52 years old (M = 30.0 years old) participated in the study. The research was conducted in a natural driving situation, and the drivers' eye movements were monitored and recorded using an eye tracking system. The results show that the influence of traffic density on the glance duration and scan duration is more significant when merging than when exiting. The results also demonstrate that the number of glances and the mean glance duration are mainly related to the driving task (e.g., the merging period). Therefore, drivers' visual search strategies mainly depend on the current driving task. With regard to driving behavior, the variation tendencies of the duration and the velocity of each period are similar. These results support building an automated driving assistant system that can automatically identify gaps and accelerate or decelerate the car accordingly or provide suggestions to the driver to do so. PMID- 27657890 TI - Enhancing the Flexibility of TCP in Heterogeneous Network. AB - Due to a set of constant initial values, the performance of conventional TCP drops significantly encountering heterogeneous network, showing low throughput and unfairness. This paper firstly demonstrates the chaotic character of TCP congestion control in heterogeneous network, especially the sensitivity to initial value. Inspired by merit of nature-inspired algorithm, a novel structure of TCP congestion control (IPPM, Internet Prey-Predator Model) is proposed. Parameters such as available link capacity(C), congestion window (W) and queue length (Q) are collected by IPPM, which calculates the max value of C according to the interacting relationship existing in C, W and Q, and IPPM initiates the TCP ssthresh with the calculated value. Plenty of simulation results show that the modified TCP can effectively avoid network congestion and packet loss. Besides, it holds high resource utilization, convergence speeds, fairness and stability. PMID- 27657889 TI - Ivermectin induces PAK1-mediated cytostatic autophagy in breast cancer. AB - Ivermectin is a broad-spectrum antiparasitic drug that has recently been demonstrated to exhibit potent anticancer activity against colon cancer, ovarian cancer, melanoma and leukemia. However, the molecular mechanism underlying this anticancer effect remains poorly understood. We recently found that ivermectin markedly inhibits the growth of breast cancer cells by stimulating cytostatic macroautophagy/autophagy in vitro and in vivo. Ivermectin inhibits the AKT-MTOR signaling pathway by promoting ubiquitination-mediated degradation of PAK1 (p21 [RAC1] activated kinase 1), leading to increased autophagic flux. Together, our work unravels the molecular mechanism underpinning ivermectin-induced cytostatic autophagy in breast cancer, and characterizes ivermectin as a potential therapeutic option for breast cancer treatment. PMID- 27657891 TI - Impact of breathing patterns on the quality of life of 9- to 10-year-old schoolchildren. AB - BACKGROUND: Mouth breathing can cause a set of changes in craniofacial growth and development, with esthetic, functional, and psychological repercussions. OBJECTIVE: To determine the impact of mouth breathing on the quality of life of schoolchildren. METHODS: A school-based, cross-sectional study was conducted with 1911 children ages 9 and 10 years in the city of Recife, Brazil. The children answered the Mouth Breather Quality of Life questionnaire and a questionnaire that addressed sociodemographic data and health-related aspects. Clinical examinations were performed by an examiner who had undergone a training and calibration process for the diagnosis of mouth breathing (kappa = 0.90). Descriptive statistics were conducted to characterize the sample. Statistical analysis involved the Student's t-test and the F test (analysis of variance) (alpha = 5%). RESULTS: The prevalence of mouth breathing was 54.81%. Children with oral breathing demonstrated a poorer quality of life in comparison with children with nasal breathing (p < 0.001). The following variables were significantly associated with a poorer quality of life among the children with mouth breathing: a younger age (p < 0.001) and the use of medication (p = 0.002). CONCLUSION: Based on the present findings, children with the mouth-breathing pattern experience a greater negative impact on quality of life in comparison with those with the nose-breathing pattern. Thus, the early diagnosis and treatment of this clinical condition are fundamental to minimizing the consequences of mouth breathing on the quality of life of schoolchildren with respiration disorders. PMID- 27657892 TI - Sinonasal polyposis in the elderly. AB - BACKGROUND/OBJECTIVE: The main end point of this investigation was to review our experience gained from 2009 to 2015 of treating chronic rhinosinusitis with nasal polyps (CRSwNP) in elderly patients (>=65 years old) with functional endoscopic sinus surgery. Secondary aims were to analyze the prognostic variables for CRSwNP in elderly patients and to compare the demographic, clinical, laboratory, histologic, and prognostic characteristics of CRSwNP in elderly versus young adult patients (20-40 years old). METHODS: Forty-three consecutive elderly patients and 71 consecutive young adult patients with CRSwNP were enrolled. RESULTS: Significant associations were found in the elderly group between CRSwNP recurrence and allergy (p = 0.037), CRSwNP recurrence and asthma (p = 0.017), and CRSwNP recurrence and acetyl salicylic acid (ASA) intolerance (p = 0.032) but not between recurrence and eosinophilic/noneosinophilic CRSwNP histology. Significant associations emerged in the young adult group between CRSwNP recurrence and asthma (p = 0.009), and ASA intolerance (p = 0.016), and serum eosinophil count (p = 0.02). The recurrence rate was also significantly higher for young adult patients with eosinophilic-type CRSwNP (p = 0.001). CRSwNP recurred less often in the elderly than in the young adult patients (p = 0.05). CONCLUSION: The present preliminary investigation found a lower recurrence rate after functional endoscopic sinus surgery for CRSwNP in elderly patients than in young adult patients. Further investigations on larger, prospective series are mandatory to support the hypothesis that, although eosinophilic-type CRSwNP is generally considered a variant at high risk of recurrence and that probably warrants stricter postoperative follow-up and adjuvant postoperative medical treatment, these considerations could not be applied to elderly patients. PMID- 27657893 TI - Mucocele formation after surgical treatment of inverted papilloma of the frontal sinus drainage pathway. AB - BACKGROUND: Inverted papillomas (IP) inserted in the frontal sinus and/or recess may be treated by using an endoscopic endonasal or an external approach. There are still few data available on this uncommon localization of IPs. OBJECTIVE: To report our experience in the management of IP of the frontal drainage pathway, to describe a previously unreported specific complication of this surgery, and to discuss the optimal surgical strategy. METHODS: A retrospective study of the patients at a tertiary care center between 2004 and 2014 who were operated on for an IP with an insertion in the frontal recess and/or the frontal sinus. Clinical charts were reviewed for demographics, clinical presentation, imaging findings, surgical treatment, and outcome. RESULTS: Twenty-seven patients were included. Patients were operated on by using a purely endoscopic approach (Draf procedure; n = 14 [51.9%]) when the IP was inserted in the frontal recess and/or the frontal sinus infundibulum (with a nasoseptal-septoturbinal flap placed on the exposed bone in four patients), or by using a combined endoscopic and open approach (osteoplastic flap procedure; n = 13 [48.1%]) when the IP invaded the frontal sinus beyond the infundibulum. There were two recurrences (7.4%), with a mean follow-up of 40 months (range, 9-123 months). During follow-up, single or multiple iatrogenic frontal mucoceles were observed in 10 patients (37%), with a mean delay of 60 months (range, 27-89 months). These mucoceles occurred both after using endoscopic (n = 3) or combined (n = 7) approaches, and required a surgical treatment in eight patients. No postoperative mucocele was observed in the four patients who had had a septal flap. CONCLUSION: In our experience, an approach based on the localization of the IP insertion provided acceptable results in terms of the local control rate (92.6%). However, the significant rate of postoperative mucoceles indicated that specific strategies (such as local flaps) still need to be developed to avoid this iatrogenic complication. PMID- 27657894 TI - Impact of endoscopic dacryocystorhinostomy on sinonasal quality of life. AB - BACKGROUND: Dacryocystorhinostomy (DCR) is the criterion standard of surgical treatment for complete nasolacrimal obstruction and dacryocystitis. There has been an expansion in the indication of the endonasal DCR (eDCR), but the impact of surgical manipulating an otherwise healthy nasal mucosa on postoperative sinonasal quality of life remains unknown. The purpose of this study was to determine whether patients who underwent eDCR experienced any decrement in sinonasal quality of life. METHODS: A retrospective chart review of 44 patients who underwent eDCR between June 2012 and May 2015. The primary outcome was the total and nasal-specific domain 1 scores of the disease specific validated Sino Nasal Outcomes Test 22. Preoperative scores were compared with the postoperative scores on days 0-30, 30-90, and 90-180 visits. A subgroup analysis of patients without nasal symptoms who underwent concomitant nasal surgical procedures was also performed. RESULTS: A statistically significant increase was observed between the preoperative score and the first postoperative score (days 0-30) in both total (7.5 [0-44] to 24 [0-51], median [interquartile range]) and domain 1 (2.5 [0-11] to 9 [0-18]) scores (p = 0.0066 and p = 0.0001, respectively). In contrast, there was no statistically significant difference between the pre- and postoperative scores on days 30-90 or 90-180. Similar results were observed in the subgroup analysis. CONCLUSION: Analysis of our findings indicated that, in general, eDCR was well tolerated by patients and nasal symptom scores returned to baseline values within 30-90 days of surgery. The concomitant performance of septoplasty in the setting of asymptomatic septal deviation did not confer any long-term improvement in symptoms of nasal obstruction. PMID- 27657895 TI - Reality bites: The establishment of accountable care organizations in otolaryngology. PMID- 27657897 TI - Validation of the Nasal Mucus Index, a novel measurement of acute respiratory infection severity. AB - BACKGROUND: To assess the concurrent and predictive validity of the Nasal Mucus Index (NMI), a novel measurement of acute respiratory infection (ARI) severity. OBJECTIVE: ARI, including the common cold and influenza, imposes a great burden on individuals and society. Previous research has attempted to assess the severity of ARI with self-reported and laboratory-based measurements. Self reported measurements may introduce bias. Laboratory-based metrics are often expensive. Therefore, there is a need for non-self-reported, affordable, and validated ARI severity tests. METHODS: Participants (N = 719) with an ARI episode underwent nasal lavage on days 1 and 3. The samples were visually assessed for the amount of mucus present in the sample and were given a subsequent NMI score. Collected samples were further assessed for interleukin (IL) 8 values (in pg/mL) and polymorphonuclear neutrophils (PMN) per high-power field. The participants rated episode severity and nasal symptoms daily by using the validated Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21). A subset of nasal symptoms was used as an additional comparator. NMI scores were compared with same-day IL-8 level, PMN count, and WURSS-21 scores for concurrent validation purposes by using the Spearman rho as the index of correlation. NMI scores were correlated with overall episode severity measurements to assess predictive validity. Overall episode severity was measured as the WURSS-21 area under the curve, nasal symptoms area under the curve, and episode duration. RESULTS: The NMI score correlated significantly with the same-day IL-8 level (rho = 0.443, p < 0.001), PMN count (rho = 0.498, p < 0.001), WURSS-21 score (rho = 0.098, p = 0.004), and nasal symptom score (rho = 0.162, p < 0.001). No significant predictive correlations were found. CONCLUSION: Associations with inflammatory biomarkers and self-reported severity measurements provided evidence of concurrent validity for the novel NMI score. The NMI can be used in future research as a simple, inexpensive, non-self-reported indicator of ARI severity. PMID- 27657898 TI - Local allergic rhinitis in children: Novel diagnostic features and potential biomarkers. AB - BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of rhinitis that has been poorly studied in children. It is characterized by the same symptoms of allergic rhinitis but with the absence of markers of systemic atopy. OBJECTIVE: To identify children affected by LAR and to analyze the pathogenesis of this disease. We chose to focus our attention on interleukin (IL) and thymic stromal lymphopoietin (TSLP). METHODS: We enrolled 20 children affected by nonallergic rhinitis (negative skin-prick test results and serum specific immunoglobulin E [sIgE] values). Each patient underwent a nasal allergen provocation test (NAPT) with dust mite and grass pollen. Before and after NAPT, nasal lavage was performed to detect sIgE, IL-5, and TSLP; anterior active rhinomanometry was used to evaluate changes in nasal obstruction. RESULTS: Two patients were positive to a nonspecific NAPT and, thus, were excluded from the study. Of the remaining 18 children, 12 (66.7%) had positive results to at least one NAPT. Among these 12 patients, nasal sIgE levels for Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Lolium perenne increased significantly after NAPT (D. pteronyssinus, p < 0.005; D. farinae, p < 0.05; L. perenne, p < 0.05). Nasal IL-5 levels showed a significant increase after NAPT (p <= 0.006), and this increase was significantly higher in children who had positive NAPT results than in those patients with negative NAPT results (p <= 0.03). Among the 12 children who had a positive NAPT result, nasal TSLP was detected in 4 patients (33.3%) and its levels showed a relevant increase after NAPT, even though the difference did not reach statistical significance (p <= 0.061). CONCLUSION: Observed results raise the importance of better refining the diagnostic protocol for LAR in children. Nasal TSLP and IL-5 levels offer new insights concerning localized allergic inflammation, although the role of nasal sIgE has still to be clarified. PMID- 27657899 TI - Lymphoma of the nasal cavity and paranasal sinuses: A case series. AB - BACKGROUND: Lymphomas of the sinonasal tract are a rare and heterogeneous subset of solid sinonasal neoplasms. OBJECTIVE: To characterize, in this case series, presenting symptoms, treatment modalities, and outcomes for patients with sinonasal lymphoma within a single institution. METHODS: Retrospective patient data were collected from an academic, oncologic center and entered into a repository designed to capture outcomes for sinonasal malignancies. Patient demographics, presenting symptoms, imaging findings, treatment modalities, and health status were retrospectively extrapolated and evaluated by using Kaplan Meier estimations for survival probability. RESULTS: Patients with sinonasal lymphoma with a mean follow-up of 50 months were identified (n = 18). Histologic diagnosis included the following: diffuse large B-cell lymphoma (n = 9), natural killer/T-cell lymphoma (n = 5), follicular lymphoma (n = 1), T-cell lymphoma (n = 1), and lymphoma-not otherwise specified (n = 2). The most frequent presenting symptoms were nasal obstruction (78%), facial pain (72%), facial swelling (50%), and nasal discharge (44%). Treatment before lymphoma diagnosis included antibiotics (83%), oral steroids (22%), decongestants (22%), and topical steroids (11%). Treatment regimens after diagnosis included both chemotherapy (94%) and chemoradiotherapy (56%). Survival rates by lymphoma subtype were 56% for B-cell lymphoma and 40% for natural killer/T-cell lymphoma. Overall, 2- and 5-year survival rates were 67% and 50%, respectively. The combination of chemotherapy and radiation resulted in significantly higher survival rates (p <= 0.001) than chemotherapy alone. CONCLUSION: Sinonasal lymphomas are characterized by meager survival rates, which differ by histopathologic subtype. The diagnosis of sinonasal lymphoma is challenging because symptoms frequently parallel those of chronic rhinosinusitis. Increased awareness of these rare malignancies may improve detection and more timely treatment. Clinical trial registration NCT01332136. PMID- 27657900 TI - The Triple Aim and its implications on the management of chronic rhinosinusitis. AB - INTRODUCTION: Accountable care organizations (ACO) and alternative payment models are a sign of the change in reimbursement from fee-for-service to value-based reimbursement. The focus of health care under ACOs is represented by the Triple Aim: to improve the experience of health care, improve the health of populations, and reduce the per capita costs. Individuals with chronic rhinosinusitis (CRS) are heavy consumers of health care services. Results of recent studies have indicated that there is the potential for improved outcomes and cost savings from early surgical intervention. Adhering to the principles of the Triple Aim may signal a paradigm shift in regard to timing of intervention for CRS in certain patients. METHODS: A scoping review was performed to analyze the current literature related to management of CRS and the impact on cost, population health outcomes, and the patient's experience of health care. RESULTS: A growing body of literature indicates that, in appropriately selected patients, when compared with medical management, endoscopic sinus surgery has the potential to improve patient outcomes and reduce the long-term cost burden of CRS. CONCLUSION: With the advent of ACOs, a paradigm shift in the treatment of CRS is inevitable to better conform to the goals of the Triple Aim. Future treatment algorithms will need to account for the heterogeneity within CRS and seek to identify appropriate timing and interventions for patients on an individual basis if the value of health care is to be improved. PMID- 27657896 TI - New insights into upper airway innate immunity. AB - BACKGROUND: Protecting the upper airway from microbial infection is an important function of the immune system. Proper detection of these pathogens is paramount for sinonasal epithelial cells to be able to prepare a defensive response. Toll like receptors and, more recently, bitter taste receptors and sweet taste receptors have been implicated as sensors able to detect the presence of these pathogens and certain compounds that they secrete. Activation of these receptors also triggers innate immune responses to prevent or counteract infection, including mucociliary clearance and the production and secretion of antimicrobial compounds (e.g., defensins). OBJECTIVE: To provide an overview of the current knowledge of the role of innate immunity in the upper airway, the mechanisms by which it is carried out, and its clinical relevance. METHODS: A literature review of the existing knowledge of the role of innate immunity in the human sinonasal cavity was performed. RESULTS: Clinical and basic science studies have shown that the physical epithelial cell barrier, mucociliary clearance, and antimicrobial compound secretion play pivotal innate immune roles in defending the sinonasal cavity from infection. Clinical findings have also linked dysfunction of these defense mechanisms with diseases, such as chronic rhinosinusitis and cystic fibrosis. Recent discoveries have elucidated the significance of bitter and sweet taste receptors in modulating immune responses in the upper airway. CONCLUSION: Numerous innate immune mechanisms seem to work in a concerted fashion to keep the sinonasal cavity free of infection. Understanding sinonasal innate immune function and dysfunction in health and disease has important implications for patients with respiratory ailments, such as chronic rhinosinusitis and cystic fibrosis. PMID- 27657901 TI - Development of a novel T-tube frontal sinus irrigation catheter. AB - BACKGROUND: The problem of postoperative management after frontal sinus surgery remains a challenge. The bilateral opening created in the Draf III procedure does not fit any currently available stent, and patients find rinsing the frontal sinus difficult, which thus decreases compliance. The objective of this study was to demonstrate the successful use of a novel frontal sinus catheter fashioned from a biliary T tube by addressing these issues in patients with complicated sinus disease. METHODS: This was a review of 30 patients who underwent a Draf III procedure between January and October 2014, and who had a T-tube stent inserted at the end of the procedure. Patient charts were analyzed for complications such as bleeding, infection, and restenosis as well as indications of ease of rinsing ability after surgery. RESULTS: From the chart data, there was only one intraoperative bleed and only one postoperative bleed that required packing. Four patients had infections that required antibiotics after surgery. At the time of data collection, only one patient had signs of restenosis as judged by the operating surgeon. Patients reported an ease of rinsing ability with the T-tube stent. CONCLUSIONS: The novel biliary T-tube stent use presented in this article is a promising future direction for postoperative care after extended frontal sinus surgery. PMID- 27657902 TI - Open versus endoscopic medial orbital decompression: Utilization, cost, and operating room time. AB - BACKGROUND: The advent of endoscopic sinus surgery has created an exciting interface between rhinology and ophthalmology in the area of orbital and optic nerve decompression Objectives: (1) To study the utilization of open versus endoscopic medial orbital decompression based on geography and indication, (2) to describe the demographics of the patient populations who underwent these different techniques, and (3) to compare outcomes, including mean charges and operating room (OR) times Methods: Cases identified by Current Procedural and Terminology codes were extracted from the California, Florida, Maryland, and New York State Ambulatory Surgery Databases from 2009 to 2011. Patient demographics, diagnoses, mean charge, and OR time were compared. RESULTS: A total of 1009 patients underwent orbital decompression; 93.0% of cases involved the medial wall only; 22.9% of medial decompressions were performed endoscopically, 74.5% were open, and 2.6% were via combined approach. Eighty percent of patients had thyroid eye disease. Analyses adjusted for sex, age, race, state, and diagnosis found that surgeries for infection (N = 47) were more likely to be performed endoscopically compared with procedures for other diagnoses (N = 962) (odds ratio 5.27 [2.67-10.40], p < 0.001). Patients in Florida were more likely to undergo endoscopic decompression compared with patients in California (odds ratio 2.35 [1.42-3.62]). The difference in median charge for endoscopic ($13,119) versus open ($11,291; p = 0.085) procedures was not significant on bivariate analysis but was significant on multivariate analysis (p = 0.04). The median OR time for open procedures was, on average, 33 minutes shorter (endoscopic, 132 minutes; open, 98 minutes; p <= 0.001) on bivariate analysis but was not significantly different when controlling for covariables (p = 0.08). CONCLUSION: In the study sample, endoscopic orbital decompression was performed in 22.9% of patients, with significant variation in surgical technique based on geography and indication. Procedures that used endoscopic compared with open decompression techniques had no significant difference in charge on bivariate analysis. The OR time for open procedures was shorter on bivariate but not on multivariate analysis. Further research is required regarding the relative effectiveness of open versus endoscopic surgical techniques for various indications. PMID- 27657903 TI - Layered sellar reconstruction with avascular free grafts: Acceptable alternative to the nasoseptal flap for repair of low-volume intraoperative cerebrospinal fluid leak. AB - BACKGROUND: Although the nasoseptal flap has become the method of choice for reconstruction of intraoperative cerebrospinal fluid (CSF) leak in endoscopic minimally invasive surgery of the skull base, layered avascular graft techniques, including allografts and middle turbinate mucosal autografts, may provide comparable reconstructive success with decreased nasal morbidity. OBJECTIVE: To describe a method of reconstruction of intraoperative CSF leak in endoscopic surgery of the sella turcica and analyze its postoperative success rate and associated comorbidities. METHODS: A retrospective review of expanded endonasal sellar tumor resections from 2008-2014 was performed, and cases of layered intraoperative skull base reconstruction with avascular free grafts were identified. Demographic factors and comorbidities that predisposed to reconstruction failure (obstructive sleep apnea, obesity) were determined. Reconstruction-related nasal complications were also identified. Postoperative CSF leak rate was determined, and statistical analysis was performed to identify predictive factors for reconstructive failure. RESULTS: Seventy-three cases were identified. Layered closure with avascular free grafts was performed. There were five cases of postoperative CSF leak (6.85%). The mean follow-up was 19 months (range, 1-76 months). Intraoperative high-flow CSF leak was a significant predictor of reconstruction failure on univariate (odds ratio 22 [95% confidence interval, 2.26-214]; p = 0.008) and multivariate analysis (odds ratio 33.6 [95% confidence interval, 2.30-492]; p = 0.010). There were no significant differences in postoperative leak rates among bony overlay graft types. There were five patients (7.9%) who experienced persistent crusting after surgery. There were no significant differences in crusting rates between allografts and mucosal grafts. There were no postoperative mucoceles. CONCLUSION: In cases of low-volume intraoperative CSF leak, layered skull base repair with avascular free grafts was an acceptable alternative to the nasoseptal flap, which may reduce prolonged sinonasal healing and donor-site morbidities. PMID- 27657904 TI - Otolaryngology. PMID- 27657905 TI - Sifting and Winnowing through Human Cytomegalovirus Lytic Replication and Latency. PMID- 27657906 TI - miRNA29 Promotes Viral Replication During Early Stage of PRRSV Infection In Vitro. AB - miRNAs are involved in various biological processes, such as host-virus interactions and antiviral immunity. In this study, we investigated the role of miR-29 on porcine reproductive and respiratory syndrome virus (PRRSV) replication and its target genes. At first, miR-29a/b-1/c expression was detected when porcine alveolar macrophages (PAMs) were infected with PRRSV at different infective doses by real time-quantitative polymerase chain reaction (RT-qPCR). The result showed that miR-29a/b-1 expression significantly increased after 6 h (p < 0.01), with the peak around 24 h, miR-29c expression in each period of PRRSV infection was very low. Then, pre-miR-29a/b-1 lentiviral vectors were constructed. Absolute RT-qPCR analysis showed that PAMs transfected with pre-miR 29a/b-1 lentiviral vectors significantly promoted PRRSV replication in PAM within 24 h (p < 0.01). The expression of the target genes (AKT3, TP53INP1, and RPS6KB1) of miR-29a significantly reduced (p < 0.01). Western blot analysis showed that AKT3 and TP53INP1 are reduced at miR-29a overexpression. To further validate the interaction between miR-29a and its target gene sites, the luciferase assay results demonstrated that miR-29a interacted with AKT3 3'UTR 1676 and 1261 sites, leading the inhibition of luciferase expression. Our findings support that miR 29a could promote PRRSV replication during early stage of virus infection in vitro and AKT3 could be the target gene of miR-29a. PMID- 27657907 TI - Bromodomain and Extra Terminal (BET) Inhibitor Suppresses Macrophage-Driven Steroid-Resistant Exacerbations of Airway Hyper-Responsiveness and Inflammation. AB - BACKGROUND: Exacerbations of asthma are linked to significant decline in lung function and are often poorly controlled by corticosteroid treatment. Clinical investigations indicate that viral and bacterial infections play crucial roles in the onset of steroid-resistant inflammation and airways hyperresponsiveness (AHR) that are hallmark features of exacerbations. We have previously shown that interferon gamma (IFNgamma) and lipopolysaccharide (LPS) cooperatively activate pulmonary macrophages and induce steroid-resistant airway inflammation and AHR in mouse models. Furthermore, we have established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation of asthma, which exhibits macrophage dependent, steroid-resistant lung disease. Emerging evidence has demonstrated a key role for bromo- and extra-terminal (BET) proteins in the regulation of inflammatory gene expression in macrophages. We hypothesised that BET proteins may be involved in the regulation of AHR and airway inflammation in our steroid resistant exacerbation models. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of a BET inhibitor (I-BET-762) on the development of steroid resistant AHR and airway inflammation in two mouse models. I-BET-762 administration decreased macrophage and neutrophil infiltration into the airways, and suppressed key inflammatory cytokines in both models. I-BET treatment also suppressed key inflammatory cytokines linked to the development of steroid resistant inflammation such as monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived protein chemokine (KC), IFNgamma, and interleukin 27 (IL 27). Attenuation of inflammation was associated with suppression of AHR. CONCLUSIONS/SIGNIFICANCE: Our results suggest that BET proteins play an important role in the regulation of steroid-resistant exacerbations of airway inflammation and AHR. BET proteins may be potential targets for the development of future therapies to treat steroid-resistant inflammatory components of asthma. PMID- 27657908 TI - Rebuttal from Dr. Hofman and Dr. Ilie. PMID- 27657909 TI - Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa. AB - BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid. PMID- 27657910 TI - Genetic characterization and antimicrobial resistance of Staphylococcus aureus isolated from bovine milk in Tunisia. AB - : Staphylococcus aureus is a major agent of bovine mastitis in dairy herds, causing economic losses in dairy industry worldwide. In addition, milk and milk products contaminated by Staph. aureus can cause harmful human diseases. The aim of this study was to characterize Staph. aureus strains isolated from dairy farms in Tunisia. Bulk tank milk (n = 32) and individual cow milk (n = 130) samples were collected during the period of 2013-2014. Forty-three Staph. aureus isolates were recovered and typed by spa typing, 16S-23S rRNA intergenic spacer (RS-PCR) and multiplex PCRs for 22 virulence genes. Antimicrobial resistance was also investigated with a disc diffusion test. A selected subsample of 22 strains was additionally genotyped by multilocus sequence typing. Seventeen spa types were recovered, and t2421 (n = 10), t521 (n = 6) and t2112 (n = 5) were the most common. Fourteen different RS-PCR genotypes grouped into 11 clusters were detected in our study, with predominance of the RVI genotype (n = 24). Eight sequence types were identified and Clonal Complex 97, corresponding to RS-PCR cluster R, was the most common (n = 10), followed by CC1 (n = 4), CC15 (n = 3) and other four accounting for one or two strains. Different combinations of virulence genes were reported, and enterotoxin genes were present in few strains (seh, n = 4; sea, n = 2; sea and seh, n = 2; sec and sel, n = 2). The majority of strains were resistant only to penicillin; only one strain was found to be multiresistant and no methicillin-resistant Staph. aureus was demonstrated. Our study reported the isolation of CC97 from bovine milk in Tunisia for the first time and confirmed the relevance of this lineage in intramammary infection in cows. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper describes the characteristics of Staphylococcus aureus isolated from bulk tank and individual cow milk in Tunisia. All strains were genotyped by spa typing and RS-PCR, a method based on the amplification of the 16S-23S rRNA intergenic spacer region, and multiplex PCRs for 22 virulence genes. A selected subsample of strains was also genotyped by multilocus sequence typing. All strains were tested for antimicrobial resistance. Our study evidences a predominance of strains belonging to Clonal Complex 97. Methicillin-resistant strains were not detected, and overall low level of antimicrobial resistance was reported. PMID- 27657912 TI - Difference in Leukocyte Composition between Women before and after Menopausal Age, and Distinct Sexual Dimorphism. AB - There are sex differences in many inflammatory and immune diseases, and the differences tend to diminish after menopause. The underlying reasons are unclear, but sex hormone levels are likely to be an important factor. Blood leukocyte count and composition provide an indicator of the inflammatory and immune status of an individual. We performed a cross-sectional analysis of blood leukocyte data from 46,879 individuals (26,212 men and 20,667 women, aged 18 to 93 years) who underwent a routine health checkup. In women aged around 50 years, neutrophil percentage (NE%) dropped whilst lymphocyte percentage (LY%) rose. Accordingly, women before age 50 had significantly higher NE%, lower LY%, and higher neutrophil-to-lymphocyte ratio (NLR) than women of 51-70 years of age (p = 1.35*10-82, p = 5.32*10-100, and p = 1.25*10-26, respectively). In age groups of <50 years, women had higher NE%, lower LY% and higher NLR than men (p = 1.82*10 206, p = 1.46*10-69, and p = 2.30*10-118, respectively), whereas in age groups of >51 years, it was the reverse (p = 1.92*10-15, p = 1.43*10-84, and p = 1.51*10 48, respectively). These results show that blood leukocyte composition differs between women before and after menopausal age, with distinct sexual dimorphism. PMID- 27657911 TI - MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early-life adversity. AB - Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. (c) 2016 Wiley Periodicals, Inc. PMID- 27657914 TI - Alternative splicing of the receptor-like kinase Nt-Sd-RLK in tobacco cells responding to lipopolysaccharides: suggestive of a role in pathogen surveillance and perception? AB - Nt-Sd-RLK encodes an S-domain lectin receptor-like kinase that is induced in response to microbe-associated molecular pattern molecules (MAMPs) such as lipopolysaccharide (LPS). In this study, we investigated the alternative splicing of Nt-Sd-RLK in response to LPS stimulation. Our data indicate that in nonstimulated cells, a shorter transcript of Nt-Sd-RLK is generated and that in response to LPS, alternative splicing produces the full-length transcript. We propose that the extracellular domain of Nt-Sd-RLK encoded by the shorter transcript functions in pathogen surveillance. Once this domain binds LPS, alternative splicing generates the kinase domain-containing Nt-Sd-RLK that activates downstream signalling leading to a defence response. Thus, our findings suggest that plant defence signalling may be regulated through the alternative splicing of receptor-like kinases involved in pathogen recognition. PMID- 27657913 TI - Production Conditions Affect the In Vitro Anti-Tumoral Effects of a High Concentration Multi-Strain Probiotic Preparation. AB - A careful selection of the probiotic agent, standardization of the dose and detailed characterization of the beneficial effects are essential when considering use of a probiotic for the dietary management of serious diseases. However, changes in the manufacturing processes, equipment or facilities can result in differences in the product itself due to the live nature of probiotics. The need to reconfirm safety and/or efficacy for any probiotic product made at a different factory is therefore mandatory. Recently, under the brand VSL#3(r), a formulation produced by a manufacturer different from the previous one, has been commercialized in some European countries (the UK and Holland). VSL#3 is a high concentration multi-strain preparation which has been recognized by the main Gastroenterology Associations for the dietary management of pouchitis as well as ulcerative colitis. We have compared the "original" VSL#3 produced in USA with the "newfound" VSL#3 produced in Italy. According to our results, the "newfound" VSL#3 has 130-150% more "dead bacteria" compared to the "original" product, raising concerns for the well-known association between dead microbes with adverse effects. The abilities of bacterial lysates from the two formulations to influence in vitro viability and proliferation of different tumor cell lines also resulted different. The repair of previously scratched monolayers of various adherent tumor cell lines (i.e. HT1080, and Caco-2 cells) was inhibited more significantly by the "original" VSL#3 when compared to the "newfound" VSL#3. Tumor cell cycle profile, in particular cell cycle arrest and apoptotic death of the cancer cells, further confirms that the "original" VSL#3 has a better functional profile than the "newfound" VSL#3, at least in in vitro. Our data stress the importance of the production conditions for the "newfound" VSL#3 considering that this product is intended to be used for the dietary management of patients with very serious diseases, such as chronic inflammatory bowel diseases. PMID- 27657915 TI - DNA Barcoding Reveals High Cryptic Diversity of the Freshwater Halfbeak Genus Hemirhamphodon from Sundaland. AB - DNA barcoding of the cytochrome oxidase subunit I (COI) gene was utilized to assess the species diversity of the freshwater halfbeak genus Hemirhamphodon. A total of 201 individuals from 46 locations in Peninsular Malaysia, north Borneo (Sarawak) and Sumatra were successfully amplified for 616 base pairs of the COI gene revealing 231 variable and 213 parsimony informative sites. COI gene trees showed that most recognized species form monophyletic clades with high bootstrap support. Pairwise within species comparisons exhibited a wide range of intraspecific diversity from 0.0% to 14.8%, suggesting presence of cryptic diversity. This finding was further supported by barcode gap analysis, ABGD and the constructed COI gene trees. In particular, H. pogonognathus from Kelantan (northeast Peninsular Malaysia) diverged from the other H. pogonognathus groups with distances ranging from 7.8 to 11.8%, exceeding the nearest neighbor taxon. High intraspecific diversity was also observed in H. byssus and H. kuekanthali, but of a lower magnitude. This study also provides insights into endemism and phylogeographic structuring, and limited support for the Paleo-drainage divergence hypothesis as a driver of speciation in the genus Hemirhamphodon. PMID- 27657916 TI - Caffeine Positively Modulates Ferritin Heavy Chain Expression in H460 Cells: Effects on Cell Proliferation. AB - Both the methylxanthine caffeine and the heavy subunit of ferritin molecule (FHC) are able to control the proliferation rate of several cancer cell lines. While caffeine acts exclusively as a negative modulator of cell proliferation, FHC might reduce or enhance cell viability depending upon the different cell type. In this work we have demonstrated that physiological concentrations of caffeine reduce the proliferation rate of H460 cells: along with the modulation of p53, pAKT and Cyclin D1, caffeine also determines a significant FHC up-regulation through the activation of its transcriptional efficiency. FHC plays a central role in the molecular pathways modulated by caffeine, ending in a reduced cell growth, since its specific silencing by siRNA almost completely abolishes caffeine effects on H460 cell proliferation. These results allow the inclusion of ferritin heavy subunits among the multiple molecular targets of caffeine and open the way for studying the relationship between caffeine and intracellular iron metabolism. PMID- 27657917 TI - Increased Pain Communication following Multiple Group Memberships Salience Leads to a Relative Reduction in Pain-Related Brain Activity. AB - Pain is a fundamental human experience that triggers a range of social and psychological responses. In this study, we present behavioral and fMRI data to examine the effect of multiple group memberships salience on reported and neural indices of pain. We found that participants expressed higher levels of pain when more social group memberships were salient. This is consistent with the notion that pain itself motivates people to communicate their pain, and more so when multiple psychological resources are salient. In addition, fMRI results reveal an interesting twist: when participants increased their pain reporting as group memberships increased (from one group to four), there was a corresponding relative reduction in dorsal anterior cingulate cortex and anterior insula activation. These results provide evidence for an adaptive response to pain: the more people make use of the social resources at their disposal when experiencing pain, the less pain areas are activated. PMID- 27657918 TI - VfoldCPX Server: Predicting RNA-RNA Complex Structure and Stability. AB - RNA-RNA interactions are essential for genomic RNA dimerization, mRNA splicing, and many RNA-related gene expression and regulation processes. The prediction of the structure and folding stability of RNA-RNA complexes is a problem of significant biological importance and receives substantial interest in the biological community. The VfoldCPX server provides a new web interface to predict the two-dimensional (2D) structures of RNA-RNA complexes from the nucleotide sequences. The VfoldCPX server has several novel advantages including the ability to treat RNAs with tertiary contacts (crossing base pairs) such as loop-loop kissing interactions and the use of physical loop entropy parameters. Based on a partition function-based algorithm, the server enables prediction for structure with and without tertiary contacts. Furthermore, the server outputs a set of energetically stable structures, ranked by their stabilities. The results allow users to gain extensive physical insights into RNA-RNA interactions and their roles in RNA function. The web server is freely accessible at "http://rna.physics.missouri.edu/vfoldCPX". PMID- 27657919 TI - Findings of Esophagography for 25 Patients After Peroral Endoscopic Myotomy for Achalasia. AB - OBJECTIVE: The purpose of this study is to better characterize the findings of esophagography after peroral endoscopic myotomy for achalasia. MATERIALS AND METHODS: We evaluated 25 patients who underwent peroral endoscopic myotomy for achalasia. The findings noted on pre- and postprocedural esophagrams were reviewed retrospectively and were correlated with clinical outcomes. RESULTS: None of the patients had esophageal perforation noted on esophagrams obtained after myotomy, and all but two patients had a hospital stay that lasted 1 day only. Esophagrams obtained on postoperative day 1 revealed endoscopic clips in 25 patients (100%), pneumoperitoneum in 18 (72%), retroperitoneal gas in 10 (40%), gastric pneumatosis in nine (36%), intramural dissections in seven (28%), and pneumomediastinum in four (16%). Repeat esophagrams obtained 3 weeks later for 22 of the patients revealed endoscopic clips in 16 patients (73%) and intramural dissections in five patients (23%), but the remaining findings had resolved. Eighteen patients (72%) had a successful myotomy and seven (28%) had suboptimal results on the basis of clinical outcomes. Observation of a distal esophageal width of 5 mm or less on postprocedural esophagrams was often associated with suboptimal results. CONCLUSION: Peroral endoscopic myotomy is a novel procedure that is less invasive than is laparoscopic Heller myotomy for the treatment of achalasia, with fewer complications and shorter recovery times. Radiologists should be aware of the findings expected on esophagography (including pneumoperitoneum, retroperitoneal gas, gastric pneumatosis, intramural dissections, and pneumomediastinum) and should also know that fluoroscopic studies may be helpful for predicting patient outcomes on the basis of the width of the distal esophagus after myotomy. PMID- 27657920 TI - A Novel Model of P-Glycoprotein Inhibitor Screening Using Human Small Intestinal Organoids. AB - P-glycoprotein (P-gp), an important efflux transporter in intestine, regulates the bioavailability of orally taken drugs. To develop an in vitro model that preferably mimics the physiological microenvironment of human intestine, we employed the three-dimensionally (3D) cultured organoids from human normal small intestinal epithelium. It was observed that the intestinal crypts could efficiently form cystic organoid structure with the extension of culture time. Furthermore, the physiological expression of ABCB1 was detected at both mRNA and protein levels in cultured organoids. Rhodamine 123 (Rh123), a typical substrate of P-gp, was actively transported across 3D organoids and accumulated in the luminal space. This transport process was also inhibited by verapamil and mitotane. In summary, the above-mentioned model based on human small intestinal 3D organoids is suitable to imitate the small intestinal epithelium and could be used as a novel in vitro model especially for P-gp inhibitor screening. PMID- 27657921 TI - Dissociating Attention Effects from Categorical Perception with ERP Functional Microstates. AB - When faces appear in our visual environment we naturally attend to them, possibly to the detriment of other visual information. Evidence from behavioural studies suggests that faces capture attention because they are more salient than other types of visual stimuli, reflecting a category-dependent modulation of attention. By contrast, neuroimaging data has led to a domain-specific account of face perception that rules out the direct contribution of attention, suggesting a dedicated neural network for face perception. Here we sought to dissociate effects of attention from categorical perception using Event Related Potentials. Participants viewed physically matched face and butterfly images, with each category acting as a target stimulus during different blocks in an oddball paradigm. Using a data-driven approach based on functional microstates, we show that the locus of endogenous attention effects with ERPs occurs in the N1 time range. Earlier categorical effects were also found around the level of the P1, reflecting either an exogenous increase in attention towards face stimuli, or a putative face-selective measure. Both category and attention effects were dissociable from one another hinting at the role that faces may play in early capturing of attention before top-down control of attention is observed. Our data support the conclusion that certain object categories, in this experiment, faces, may capture attention before top-down voluntary control of attention is initiated. PMID- 27657922 TI - Lon Protease Is Involved in RhpRS-Mediated Regulation of Type III Secretion in Pseudomonas syringae. AB - Pseudomonas syringae depends on the type III secretion system (T3SS) to directly translocate effectors into host cells. Previously, we reported a nonpathogenic rhpS mutant, suggesting that the two-component transduction system rhpRS is an important regulator of T3SS in P. syringae. rhpRS regulates itself and a variety of downstream genes under an inverted repeat element promoter in a phosphorylation-dependent manner. Here, we identify lon as a suppressor of the rhpS mutant through transposon screening. A lon/rhpS double mutant restored the phenotypes of the rhpS mutant. The expression level of lon was higher in rhpS and other T3SS-deficient mutants than the wild-type strain, suggesting a negative feedback mechanism between lon and T3SS genes. lon was also induced by a novel T3SS inhibitor, acetate, which substantially compromises the activation of T3SS genes in minimal medium and bacterial growth in host plants. PMID- 27657923 TI - Redescription and Phylogenetic Placement of ?Hemicalypterus weiri Schaeffer, 1967 (Actinopterygii, Neopterygii) from the Triassic Chinle Formation, Southwestern United States: New Insights into Morphology, Ecological Niche, and Phylogeny. AB - The actinopterygian fish ?Hemicalypterus weiri Schaeffer, 1967 is herein redescribed and rediagnosed based on new information collected from reexamination of museum specimens as well as examination of recently collected specimens from the Upper Triassic Chinle Formation of San Juan County, Utah, United States. ?Hemicalypterus is distinguishable by its deep, disc-shaped compressed body; ganoid-scaled anterior half and scaleless posterior half; spinose, prominent dorsal and ventral ridge scales anterior to dorsal and anal fins; hem-like dorsal and anal fins with rounded distal margins; small mouth gape; and specialized, multicuspid dentition. This type of dentition, when observed in extant fishes, is often associated with herbivory, and ?Hemicalypterus represents the oldest known ray-finned fish to have possibly exploited an herbivorous trophic feeding niche. A phylogenetic analysis infers a placement of ?Hemicalypterus within ?Dapediiformes, with ?Dapediiformes being recovered as sister to Ginglymodi within holostean actinopterygians. PMID- 27657925 TI - Domestic diagnosis of newborn bilirubin levels? PMID- 27657924 TI - An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome. AB - The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5' end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, beta-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5' UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5' UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5' UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID- 27657926 TI - Group Dynamics in Automatic Imitation. AB - Imitation-matching the configural body movements of another individual-plays a crucial part in social interaction. We investigated whether automatic imitation is not only influenced by who we imitate (ingroup vs. outgroup member) but also by the nature of an expected interaction situation (competitive vs. cooperative). In line with assumptions from Social Identity Theory), we predicted that both social group membership and the expected situation impact on the level of automatic imitation. We adopted a 2 (group membership target: ingroup, outgroup) x 2 (situation: cooperative, competitive) design. The dependent variable was the degree to which participants imitated the target in a reaction time automatic imitation task. 99 female students from two British Universities participated. We found a significant two-way interaction on the imitation effect. When interacting in expectation of cooperation, imitation was stronger for an ingroup target compared to an outgroup target. However, this was not the case in the competitive condition where imitation did not differ between ingroup and outgroup target. This demonstrates that the goal structure of an expected interaction will determine the extent to which intergroup relations influence imitation, supporting a social identity approach. PMID- 27657928 TI - Correction: Improving Fishing Pattern Detection from Satellite AIS Using Data Mining and Machine Learning. AB - [This corrects the article DOI: 10.1371/journal.pone.0158248.]. PMID- 27657927 TI - Perspectives on Sleep, Sleep Problems, and Their Treatment, in People with Serious Mental Illnesses: A Systematic Review. AB - Sleep problems are common in people with serious mental illness, and impact negatively on functioning and wellbeing. To understand the development of sleep problems, their maintenance, and their treatment, an in depth understanding of patient perspectives is crucial. A systematic literature review was conducted using Medline, AMED, PsychInfo, Embase and CINAHL. Qualitative and quantitative studies were included if they explored or measured patient perspectives on sleep, sleep problems or sleep treatments in people with serious mental illness. Of the 2,067 hits, only 22 met review inclusion criteria, and high quality evidence was sparse. The limited findings suggested sleep was seen as highly interlinked with mental health. Evaluations of treatments varied, however perceived efficacy and personalisation of treatments were valued. Some evidence suggested patient priorities and conceptualisations regarding sleep may diverge from those of validated screening tools developed in general population and sleep medicine samples. More rigorous research is needed to support adaptation and development of interventions and outcome measures for use in specialist mental health settings. Qualitative studies exploring the experience of sleep disturbance in particular diagnostic groups and contexts are urgently required, as are patient perspectives on sleep interventions. PMID- 27657929 TI - JOURNAL CLUB: Longitudinal Qualitative Characterization of MRI Features After Laser Interstitial Thermal Therapy in Drug-Resistant Epilepsy. AB - OBJECTIVE: Laser interstitial thermal therapy (LITT), a method for ablating brain tissue under real-time MR thermometry, has been used more frequently in recent years to treat nonmalignant lesions. The purpose of this study is to longitudinally characterize MRI features after LITT in patients with drug resistant epilepsy, primarily in the setting of mesial temporal sclerosis. MATERIALS AND METHODS: MR images from 23 consecutive patients who underwent LITT were retrospectively reviewed. All patients had images obtained immediately after the ablation. Multiple patients had follow-up imaging at various time points after treatment, from postoperative days 7 through 1539. A total of 54 MRI studies were reviewed. RESULTS: Immediately after LITT, MR images showed a ring enhancing lesion at the ablation site with minimal surrounding edema. Seven images showed increased enhancement of the ipsilateral choroid plexus. Images in the subacute phase showed a mild increase in edema with similar enhancement. Images in the transitional phase showed a decrease in edema with variable enhancement. Images in the chronic phase showed minimal gliosis with or without cavity formation or cavity formation alone, with either decreased or no enhancement. CONCLUSION: This report describes the time course of the imaging findings after LITT for drug-resistant epilepsy. The typical stages include rim enhancing lesion with minimal edema, followed by an increase in edema, to eventual gliosis and nonenhancing cavity formation. Radiologists need to be familiar with the postablation findings to minimize misdiagnosis and prevent unnecessary workup. PMID- 27657930 TI - Safety and efficacy of IIb/IIIa inhibitors in combination with highly active oral antiplatelet regimens in acute coronary syndromes: A meta-analysis of pivotal trials. AB - The risk and benefit of GP-IIb/IIIa Inhibition (GPI) in combination with recent antiplatelet regimens in acute coronary syndromes (ACS) remain unassessed. The advent of fast-acting highly active oral P2Y12 inhibitors questions the additional value and risk of their association with GPI. We studied the effect of GPI in combination with prasugrel and ticagrelor, compared to clopidogrel on major bleeding in pivotal randomized controlled trials in the setting of ACS, using a meta-analytic approach. A similar analysis, further including the comparison of a double versus standard dose clopidogrel regimen, was performed for the risk of the primary efficacy endpoint. The combination of GPI and recent P2Y12 inhibitors was associated with a similar risk of bleeding as compared with GPI and the standard clopidogrel regimen (RR 0.92 [0.74; 1.13]). The benefit of recent regimens, including double dose clopidogrel, in reducing the primary ischemic endpoint (RR 0.86 [0.78; 0.94]) persisted in those treated with GPI. Although GPI use was associated with a consistent increase in the risk of bleeding in both recent (RR 1.27 [1.05-1.55]) and standard regimens (RR 2.01 [1.64-2.47]), the relative magnitude of such an increase was lower in association with prasugrel or ticagrelor as compared with clopidogrel. The risk of bleeding using a combination of GPI and oral antiplatelet regimens is mainly related to the use of GPI and not the oral antiplatelet regimen. Considering the absence of increased risk of bleeding and the persistence of the benefit of recent P2Y12 regimens in combination with GPI as compared with the standard clopidogrel regimen, the use of such a combination within the guidelines is supported by our findings. PMID- 27657932 TI - A new direction for spreading depolarization: Investigation in the fly brain. PMID- 27657931 TI - Comparison of Integrated Responses to Nonlethal and Lethal Hypothermal Stress in Milkfish (Chanos chanos): A Proteomics Study. AB - Milkfish is an important aquaculture species in Taiwan, and its high mortality during cold snaps in winter usually causes huge economic losses. To understand the effect of hypothermal stress and the corresponding compensatory stress response in milkfish, this study aimed to compare liver and gill protein levels between milkfish exposed to nonlethal (18 degrees C), lethal (16 degrees C), and control (28 degrees C) temperatures. Using a proteomics approach based on two dimensional electrophoresis and nano-LC-MS/MS analysis, this study identified thirty unique protein spots from milkfish livers and gills for which protein abundance was significantly different between nonlethal, lethal, and control temperature groups. Proteins identified in the liver were classified into three different categories according to their cellular function: (1) anti-oxidative stress, (2) apoptotic pathway, and (3) cytoskeleton. Similarly, proteins identified in the gill were sorted in five different functional categories: (1) cytoskeleton, (2) immune response, (3) protein quality control, (4) energy production, and (5) intracellular homeostasis. Based on functional information derived from the identified proteins, we assumed that different levels of hypothermal stress had a different effect and induced a different cellular response. Upon nonlethal hypothermal stress, the identified proteins were involved in anti-oxidative stress and anti-inflammation pathways, suggesting that milkfish had high levels of oxidative stress in the liver and exhibited inflammation response in the gill. Upon lethal hypothermal stress, however, identified proteins were associated with apoptosis in the liver and regulation of intracellular homeostasis in the gill. The present study provided evidence to illustrate different multi-physiological responses to nonlethal and lethal hypothermal stress in milkfish livers and gills. PMID- 27657934 TI - The impact of assistive technology services in post-secondary education for students with disabilities: Intervention outcomes, use-profiles, and user experiences. AB - The outcomes of assistive technology (AT) support services for post-secondary education students with disabilities are under-reported, and little is known about use-profiles and user experiences when AT interventions are applied to this rapidly growing population. We examined AT service outcomes related to performance and satisfaction of common academic tasks (using the Canadian Occupational Performance Measure [COPM]), as well as how students with disabilities use and experience AT and AT services (employing an AT-use survey). Three-hundred fifty-three students with disabilities completed the AT-use survey, with a subset of these (n = 216) also participating with pre-post AT intervention COPM assessment. COPM performance and satisfaction ratings significantly increased from pre- to post-AT intervention in all academic task categories (reading, writing, note-taking, test-taking, and studying; p < 0.001). The AT-use survey most notably revealed these students preferred face-to-face training, used their AT at least 3 days per week, used AT in a variety of environments, felt AT positively impacted their academic success, and believed they would continue using AT post-graduation. The study findings contribute to evidence-base for AT services with a hope we may improve AT services to best meet the changing needs of the growing number of college students with disabilities. PMID- 27657933 TI - Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis. AB - BACKGROUND: Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results. OBJECTIVE: To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis. METHODS: For the case control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk. RESULTS: We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76-1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95-1.99)] and a high heterogeneity (I2: 87.2%). CONCLUSIONS: The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted. PMID- 27657938 TI - Ready to do battle. AB - Last week, the Northern Regional Health Authority announced 180 redundant posts including the entire regional nursing staff. The move was part of the government's edict last month to slim down regions. PMID- 27657935 TI - Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls. AB - BACKGROUND: Conflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D) of human HFE (hereditary hemochromatosis) gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and hepatocellular carcinoma (HCC). METHODS: An updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis. RESULTS: In total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, Passociation<0.05). However, no significant difference between liver cirrhosis cases and the control group was observed for HFE C282Y and H63D (all Passociation>0.05). In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, Passociation<0.05). Moreover, a positive association between compound heterozygosity for C282Y/H63D and the risk of NAFLD and HCC, but not liver cirrhosis, was observed. CONCLUSION: Our meta-analysis provides evidence that the HFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion. PMID- 27657940 TI - Mass redundancies at Northern Region. AB - The Northern Regional Health Authority provoked outrage last week when it announced 180 redundant posts including the entire nursing division. PMID- 27657936 TI - A Nerve Conduit Containing a Vascular Bundle and Implanted With Bone Marrow Stromal Cells and Decellularized Allogenic Nerve Matrix. AB - Cells, scaffolds, growth factors, and vascularity are essential for nerve regeneration. Previously, we reported that the insertion of a vascular bundle and the implantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a nerve conduit promoted peripheral nerve regeneration. In this study, the efficacy of nerve conduits containing a vascular bundle, BM-MSCs, and thermally decellularized allogenic nerve matrix (DANM) was investigated using a rat sciatic nerve model with a 20-mm defect. Lewis rats were used as the sciatic nerve model and for the preparation of BM-MSCs, and Dark Agouti rats were used for the preparation of the DANM. The revascularization and the immunogenicity of the DANM were investigated histologically. The regeneration of nerves through nerve conduits containing vessels, BM-MSCs, and DANM (VBD group) was evaluated based on electrophysiological, morphometric, and reinnervated muscle weight measurements and compared with that of vessel-containing conduits that were implanted with BM MSCs (VB group). The DANM that was implanted into vessel-containing tubes (VCTs) was revascularized by neovascular vessels that originated from the inserted vascular bundle 5-7 days after surgery. The number of CD8+ cells found in the DANM in the VCT was significantly smaller than that detected in the untreated allogenic nerve segment. The regenerated nerve in the VBD group was significantly superior to that in the VB group with regard to the amplitude of the compound muscle action potential detected in the pedal adductor muscle; the number, diameter, and myelin thickness of the myelinated axons; and the tibialis anterior muscle weight at 12 and 24 weeks. The additional implantation of the DANM into the BM-MSC-implanted VCT optimized the axonal regeneration through the conduit. Nerve conduits constructed with vascularity, cells, and scaffolds could be an effective strategy for the treatment of peripheral nerve injuries with significant segmental defects. PMID- 27657939 TI - Staff 'duped' into accepting rationing. AB - Nurses and doctors 'seduced' into seeing rationing in the NHS as inevitable are accepting inadequate funding for health care, RCN General Secretary Christine Hancock said at a British Medical Association debate last week. PMID- 27657942 TI - Review of MH nurses' education needed. AB - Purchasing trends in the NHS mean a radical review is required of the way mental handicap nurses are prepared for practice, a DoH conference on the future of the specialty heard last week. PMID- 27657937 TI - Forecasting Human African Trypanosomiasis Prevalences from Population Screening Data Using Continuous Time Models. AB - To eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models for predicting HAT prevalence in a given village based on past observed prevalence levels and past screening activities in that village. Based on the quality of prevalence level predictions in 143 villages in Kwamouth (DRC), and based on the theoretical foundation underlying the models, we consider variants of the Logistic Model-a model inspired by the SIS epidemic model-to be most suitable for predicting HAT prevalence levels. Furthermore, we demonstrate the applicability of this model to predict the effects of planning policies for screening operations. Our analysis yields an analytical expression for the screening frequency required to reach eradication (zero prevalence) and a simple approach for determining the frequency required to reach elimination within a given time frame (one case per 10000). Furthermore, the model predictions suggest that annual screening is only expected to lead to eradication if at least half of the cases are detected during the screening rounds. This paper extends knowledge on control strategies for HAT and serves as a basis for further modeling and optimization studies. PMID- 27657943 TI - ? AB - Travel sick: Hundreds of travellers lobbied Parliament last week to fight proposals to change the 1968 Caravan Sites Act. The pressure group Maternity Alliance has warned that the plan could endanger the health of traveller mothers and babies. PMID- 27657944 TI - Jobs to go as London Trust relocates services. AB - More than 80 nurses and midwives are to lose their jobs as a London Trust hospital relocates its services, the RCN claimed last week. PMID- 27657945 TI - GP practice expelled after overspending. AB - The expulsion of a Sheffield practice from the GP fundholding scheme for failing to manage its budget could be the first of many, a nursing union has warned. PMID- 27657948 TI - Educators to help audit performance. AB - The English National Board is to ask educational institutions to help evaluate its performance in validating courses. PMID- 27657946 TI - Unions threaten legal action to speed up grading appeals. AB - Nurses unions are considering legal action to speed up the clinical grading appeals process after talks with the management side failed in reaching an agreement. PMID- 27657949 TI - Jobs threatened by plans to contract out. AB - Plans by Eastbourne Health Authority to award an elderly care contract to a private company could lead to job losses and may be detrimental to patients, the RCN has warned. PMID- 27657951 TI - ? AB - End product: A document celebrating the English National Board's tenth anniversary was launched last week at a dinner to mark the end of its term of office. From left are English National Board Chief Executive Tony Smith, ENB Chair Jean Hooper. United Kingdom Central Council Chair Dame Audrey Emerton and Chief Nursing Officer Yvonne Moores. PMID- 27657950 TI - ENB condemns new draft of Strategy as too political. AB - A Department of Health redrafting of the 1989 'Strategy for Nursing' has been condemned by the ENB for focusing on political issues, with too little reference to the contribution of the nursing professions. PMID- 27657952 TI - Helping relatives of people in nursing homes. AB - People with elderly parents in nursing homes should not feel guilty if their relatives are unhappy, a report by The Relatives Association says. Instead they should get 'on the inside' of homes and work with owners to improve the situation'. PMID- 27657953 TI - Mothers need more choice. AB - Midwives have no right to impose their views on mothers even if the mother's choice may put herself and her baby at greater risk, a King's Fund Centre report says. PMID- 27657954 TI - Dramatic number of cuts in school nurse posts revealed. AB - The number of school nurses has been slashed by a fifth since the government came to power, it emerged last week. PMID- 27657955 TI - Mental disorder committee gets one nurse. AB - The appointment of only one nurse to a 28-strong government advisory committee on mentally disordered offenders was labelled 'most disappointing' last week by the Royal College of Nursing. PMID- 27657956 TI - ? AB - Nurses from Dublin's St James Hospital at the funeral of Valerie Place, the Irish nurse murdered in Somalia last month. Ms Place was working for the humanitarian organisation Concern. PMID- 27657958 TI - Parliament. AB - Health Secretary Virginia Bottomley is being urged to consider emergency funding to help cash-strapped hospitals continue to treat patients. PMID- 27657959 TI - Link between leukaemia and nuclear industry. AB - Children of men who work in the nuclear industry may be at increased risk of leukaemia even if their fathers worked in areas where monitored radiation levels were low, evidence from the Imperial Cancer Research Fund suggests. PMID- 27657960 TI - Increased risk of coronary disease. AB - People who switch to margarine and other foods containing partially hydrogenated vegetable oils may run an increased risk of heart disease, new research suggests. PMID- 27657961 TI - ? AB - White blood cells from a patient with acute lymphoblastic leukaemia, a condition which may be linked to parental occupation, according to new research. PMID- 27657962 TI - Recommendation for licensed nicotine patches. AB - Practice nurses should recommend only licensed nicotine patches available in pharmacies, doctors at the National Addiction Centre warned last week. PMID- 27657963 TI - Fight against skin treatment cutbacks. AB - Dermatology nurses are fighting government plans to cut back on the range of skin treatments available on prescription from family doctors. PMID- 27657964 TI - Changing nurses' pay. AB - Several key elements in the government's NHS reforms are making an impact on nurses' pay. In particular, the creation of the internal market, in which the roles of purchasers and providers of health services are separated and are governed by the contracting process, gives providers an incentive to minimise the costs of their activities. With the nursing paybill accounting for roughly a third of the running costs of units, it is inevitable that tighter control of the wage bill directly through pay levels or indirectly through re-profiling will be seen as one way of gaining 'competitive' advantage. PMID- 27657965 TI - Family versus education dilemma. AB - As a mother of four, I was attracted to Project 2000 by brochures implying that I would be more than two years into the course before I had to start working shifts, and that I would receive seven weeks' holiday a year. PMID- 27657966 TI - No work after education? AB - I empathise with Katie Wood and appreciate her difficulties (Finished after finals? Nurses work campaign, February 17). Since qualifying as an RGN in Bristol in November 1991, I moved to Gloucestershire as no vacancies existed at Frenchay Hospital where I was a student. PMID- 27657967 TI - Nursing advisory group. AB - While Hugh Chadderton et al listed ways in which nurses can contribute to the purchasing cycle (Role of nurses in health purchasing, Clinical February 24), I would like to highlight another method we have developed in Camden and Islington the commissioning nursing advisory group. PMID- 27657968 TI - No radioactivity in dye. AB - I enjoyed Patricia Johnson's article on laporoscopic cholecystectomy (Clinical, February 17), but I feel I must make clear chat the 'radioactive opaque dye' used to demonstrate the biliary tree on X-ray is not in fact radioactive. PMID- 27657969 TI - Wrong time, wrong name. AB - Having just read Alan Glasper's Viewpoint, Write off sisters, (February 24), I feel compelled to say that he has missed the point. PMID- 27657970 TI - Congratulations on conference success. AB - On behalf of the RCN Ethics Forum, I would like to congratulate the Isle of Man Branch on the success of its recent three-day conference on the value of nursing. PMID- 27657971 TI - Poor standards do exist. AB - I feel I must respond to the comments made by angry care home owners and staff regarding my article, A poor substitute for care (News features January 20). PMID- 27657972 TI - All carers together after all. AB - It was good to read Josephine Greenan's over-the-top opinions on NHS nurses being pampered (Levels of skill in nursing homes, Letters, March 3). A little dispute, criticism and debate can be most helpful and stimulating. PMID- 27657973 TI - Your tributes. AB - * Dr Mo-Im Kim, President of the International Council of Nurses, has asked me to convey her deepest sympathy and that of the ICN Board of Directors and staff on the death of Robert Tiffany. PMID- 27657974 TI - Multiskilling and other hot air. AB - Hi there, Health Care Workers. How did you get on introducing multiskilling to your New Nursing Units? PMID- 27657975 TI - Let Me Decide Let Me Decide W Molloy V Mepham Penguin 48pp L3-99 0-14-017896-1. AB - Given recent events which have further fuelled debate about the status of advanced directives in health care, the publication of Let Me Decideis most timely. It offers simple yet erudite guidelines for preparing a document to indicate your wishes in the event of incapacity or crisis. Formerly, this approach was called a 'living will', but William Molloy and Virginia Mepham prefer to call it a 'let me decide' directive. PMID- 27657977 TI - Working towards Independence Working towards Independence J Carr S Collins Jessica Kingsley 266pp L14.95 1-8530-2140-7 [Formula: see text]. AB - If there were a bestseller list for practical books relating to behavioural methods of teaching people with learning disabilities, then the works of Janet Carr would justifiably occupy the top places. PMID- 27657976 TI - Shattering the glass ceiling - the woman manager M J Davidson Shattering the Glass Ceiling - the Woman Manager C L Cooper Paul Chapman Publ 184pp L12.95 1 85396-132-9. AB - Shattering the Glass Ceiling - the Woman managercould not have been published at a more opportune time. Mrs Bottomley, Secretary of State, has just announced a new bursary for nurses to provide them with the opportunity to undertake Masters in Business Administration degrees and, therefore, equip themselves with the academic knowledge and qualifications to compete for senior management posts in the NHS. PMID- 27657978 TI - Career listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27657979 TI - Web-based trauma intervention for veterans has physical health payoff in randomized trial. AB - OBJECTIVE: PTSD and depression are related to perceived physical health impairment in veterans, but little is known about the effects of psychological treatment on impairment. We examined the impact of an interactive online treatment for veterans with trauma-related distress, including (a) whether treatment effects include reduced perceived physical impairment, and (b) how these treatment effects are related to symptoms of PTSD and depression. METHOD: A randomized controlled trial assessed the impact on perceived physical health impairment of interactive online treatment for veterans with symptoms of PTSD and depression. Veterans were randomized to either the Vets Prevail program (n = 209), or a no-treatment control (n = 94) completing measures of depression and PTSD symptomology as well as perceived physical health impairment at 6 and 12 weeks following baseline assessment We conducted a series of multiple and single mediation analyses to examine how the effects of Vets Prevail on these outcomes are related. RESULTS: Compared with control, Vets Prevail was (a) associated with significant reductions in perceived physical health impairment, and (b) this relationship was mediated by reductions in symptoms of PTSD, but not depression. Further analysis showed that perceived physical health impairment also mediated the relationships between intervention and PTSD and depression symptoms. CONCLUSIONS: Findings indicate that Vets Prevail reduces perceptions of physical health impairment by reducing PTSD symptomology. It is also possible that treatment initiated more complex, bidirectional relationships such that improvements in psychological distress and in perceived physical health impairment reinforced each other over time. Findings demonstrate that Vets Prevail may help veterans overcome traditional barriers to care and achieve improvements in multiple areas of functioning. (PsycINFO Database Record PMID- 27657980 TI - Urea Mimics Nucleobases by Preserving the Helical Integrity of B-DNA Duplexes via Hydrogen Bonding and Stacking Interactions. AB - Urea lesions are formed in DNA because of free radical damage of the thymine base, and their occurrence in DNA blocks DNA polymerases, which has deleterious consequences. Recently, it has been shown that urea is capable of forming hydrogen bonding and stacking interactions with nucleobases, which are responsible for the unfolding of RNA in aqueous urea. Base pairing and stacking are inherent properties of nucleobases; because urea is able to form both, this study attempts to investigate if urea can mimic nucleobases in the context of nucleic acid structures by examining the effect of introducing urea lesions complementary to the four different nucleobases on the overall helical integrity of B-DNA duplexes and their thermodynamic stabilities using molecular dynamics (MD) simulations. The MD simulations resulted in stable duplexes without significant changes in the global B-DNA conformation. The urea lesions occupy intrahelical positions by forming hydrogen bonds with nitrogenous nucleobases, in agreement with experimental results. Furthermore, these urea lesions form hydrogen bonding and stacking interactions with other nucleobases of the same and partner strands, analogous to nucleobases in typical B-DNA duplexes. Direct hydrogen bond interactions are observed for the urea-purine pairs within DNA duplexes, whereas two different modes of pairing, namely, direct hydrogen bonds and water-mediated hydrogen bonds, are observed for the urea-pyrimidine pairs. The latter explains the complexities involved in interpreting the experimental nuclear magnetic resonance data reported previously. Binding free energy calculations were further performed to confirm the thermodynamic stability of the urea-incorporated DNA duplexes with respect to pure duplexes. This study suggests that urea mimics nucleobases by pairing opposite all four nucleobases and maintains the overall structure of the B-DNA duplexes. PMID- 27657982 TI - Molecules empowering animals to sense and respond to temperature in changing environments. AB - Adapting behavior to thermal cues is essential for animal growth and survival. Indeed, each and every biological and biochemical process is profoundly affected by temperature and its extremes can cause irreversible damage. Hence, animals have developed thermotransduction mechanisms to detect and encode thermal information in the nervous system and acclimation mechanisms to finely tune their response over different timescales. While temperature-gated TRP channels are the best described class of temperature sensors, recent studies highlight many new candidates, including ionotropic and metabotropic receptors. Here, we review recent findings in vertebrate and invertebrate models, which highlight and substantiate the role of new candidate molecular thermometers and reveal intracellular signaling mechanisms implicated in thermal acclimation at the behavioral and cellular levels. PMID- 27657981 TI - Adapting a couple-based intimacy enhancement intervention to breast cancer: A developmental study. AB - OBJECTIVE: Sexual concerns continue to be poorly addressed for women treated for breast cancer and evidence-based interventions that adequately address these concerns are scarce. The objective of this study was to adapt a telephone-based intimacy enhancement intervention, previously tested in couples facing colorectal cancer, to the needs of women with breast cancer through qualitative focus groups, cognitive interviews, and expert review. METHOD: Three semistructured qualitative focus groups in partnered posttreatment breast cancer survivors (n = 15) reporting sexual concerns were conducted to investigate experiences of breast cancer-related sexual concerns and intervention preferences. Focus group data were coded using the framework approach to qualitative analysis; 8 key themes were identified and used to develop the content and format of the intervention. Feedback from cognitive interviews with study-naive breast cancer survivors (n = 4) and expert review of materials were also incorporated in finalizing the intervention materials. RESULTS: Qualitative findings centered on the impact of breast cancer and its treatment on women's sexuality and on the intimate relationship, experiences of helpful and unhelpful coping methods, and explicit intervention preferences. Focus group data were particularly helpful in identifying the scope of educational topics and in determining how to structure intervention skills practice (e.g., intimacy-related communication) to be optimally relevant and helpful for both women and their partners. Cognitive interview feedback helped refine intervention materials. CONCLUSION: An intimacy enhancement intervention was adapted for women with breast cancer and their partners. This intervention offers a promising, potentially disseminable approach to addressing breast cancer-related sexual concerns. (PsycINFO Database Record PMID- 27657983 TI - Metabolomic analysis of NAD kinase-deficient mutants of the cyanobacterium Synechocystis sp. PCC 6803. AB - NAD kinase (NADK) phosphorylates NAD(H) to NADP(H). The enzyme has a crucial role in the regulation of the NADP(H)/NAD(H) ratio in various organisms. The unicellular cyanobacterium Synechocystis sp. PCC 6803 possesses two NADK-encoding genes, sll1415 and slr0400. To elucidate the metabolic change in NADK-deficient mutants growing under photoautotrophic conditions, we conducted metabolomic analysis using capillary electrophoresis mass spectrometry (CE-MS). The growth curves of the wild-type parent (WT) and NADK-deficient mutants (Delta1415 and Delta0400) did not show any differences under photoautotrophic conditions. The NAD(P)(H) balance showed abnormality in both mutants. However, only the metabolite pattern of Delta0400 showed differences compared to WT. These results indicated that the two NADK isoforms have distinct functions in cyanobacterial metabolism. PMID- 27657984 TI - TRPV1: A Potential Therapeutic Target for Myocardial Infarction? PMID- 27657985 TI - Comparative pharmacokinetic and pharmacodynamic evaluation between a new biosimilar and reference recombinant human growth hormone. AB - OBJECTIVE: To extend available dosing options in the treatment of growth hormone deficiency, a comparative pharmacokinetic and pharmacodynamic phase-1 clinical study involving subcutaneous administration of growth hormone was conducted. DESIGN: The test formulation (biosimilar recombinant human growth hormone; r-hGH; Somatotropin) and reference formulation (Genotropin(r)) were tested in 38 adult healthy subjects after their subcutaneous administration of 12.8IU in an open label, single dose, randomized, two period cross over study separated with a washout period of 11days. Endogenous growth hormone release was suppressed by a continuous Octreotide infusion up to 24h after r-hGH administration. All the subjects were evaluated for local tolerance using Wong-Baker Faces pain rating scale and an injection site reaction (ISR) score. Detection of serum levels of r hGH, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was done by suitable validated bio-analytical methods. Assessment of bioequivalence for pharmacokinetic parameters was done using log transformed area under the curve (AUC) and maximum concentration (Cmax) for r hGH. The pharmacodynamic assessment was done by comparing the area under the effect-time curve (AUEClast) and maximum measured effect concentration (Emax) of IGF-1 and IGFBP-3. RESULTS: The biosimilar formulation of recombinant human growth hormone fulfilled the predefined bioequivalence criteria for pharmacokinetic and pharmacodynamic parameters. CONCLUSION: The new biosimilar recombinant human growth hormone bears the potential to become an alternative option for the treatment of growth hormone deficiency. PMID- 27657987 TI - Broad-Spectrum Noncompetitive Immunocomplex Immunoassay for Cyanobacterial Peptide Hepatotoxins (Microcystins and Nodularins). AB - A broad-spectrum noncompetitive immunoassay allowing sensitive and simple detection of a group of similar compounds would be an ideal tool for screening low-molecular weight analytes (<2000 Da) having many variants. However, the development of an essential antibody pair capable of sandwich-type recognition of the analytes' small generic core structure is a demanding task due to limited space available for simultaneous binding of two different antibodies. We report here a generic noncompetitive assay for cyanobacterial microcystins (MCs) and nodularins (Nod), a group of structurally related small cyclic peptides (~1000 Da) with more than 100 naturally occurring analogs. The assay is based on the unique combination of a generic anti-immunocomplex (anti-IC) single-chain fragment of antibody variable domain (scFv) and a monoclonal antibody capable of binding to an Adda-group (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca 4(E),6(E)-dienoic acid) present in all MCs/Nod. The anti-IC scFv was isolated from a large synthetic antibody library with phage display and used to develop a single-step sandwich-type noncompetitive immunocomplex assay. The sensitive time resolved immunofluorometry-based assay is capable of detecting all the 11 tested commonly occurring hepatotoxins (MC-LR, -dmlR, -RR, -dmRR, -LA, -LY, -LF, -LW, YR, -WR, and Nod-R) at concentration below 0.1 MUg/L in a 1 h assay. Using MC-LR, the most studied toxic and widely distributed of the toxins, the calculated detection limits (based on blank + 3SD response) are ~0.026 MUg/L in 1 h and ~0.1 MUg/L in 10 min assay time. This is by far the fastest reported immunoassay for MCs and Nod with a detection limit far below the World Health Organization's guideline limit (1 MUg/L of MC-LR equivalent in drinking water). The assay was validated with spiked tap and lake water as well as with environmental surface water samples. The developed assay provides a simple, rapid, and highly sensitive tool for the quantitative detection of MCs/Nod with the additional benefit of automation and high-throughput possibilities for large scale screening of drinking and environmental surface water samples. Furthermore, the study describes the first demonstration of the assay intended for the detection of an analyte group comprising similar low-molecular weight compounds exhibiting the benefits of a reagent excess type assay. PMID- 27657988 TI - Forest soils in France are sequestering substantial amounts of carbon. AB - The aim of this study was to assess whether French forest soils are sources or sinks of carbon and to quantify changes in soil organic carbon (SOC) stocks over time by resampling soil in long-term forest monitoring plots. Within each plot, and for each survey, soils were sampled at five points selected in five subplots and divided into layers. Composite samples were produced for each layer and subplot, then analysed for mass, bulk density and SOC. Linear mixed models were used to estimate SOC changes over 15years between two soil surveys carried out in 102 plots in France. A factor analysis and a budget approach were also used to identify which factors and processes were primarily responsible for SOC dynamics. Forest soils throughout France substantially accumulated SOC (+0.35MgCha-1yr-1) between 1993 and 2012. The SOC sequestration rate declined with stand age and was affected by stand structure. Uneven-aged stands sequestered more SOC than did even-aged stands (p<0.001). For the forest floor, the SOC sequestration rate estimated by the budget approach was in agreement with that based on stock comparison. This increasing SOC stock in the forest floor can be explained by recent changes in certain factors affecting litter decomposition (climate and litter quality). For the mineral soil, the budget approach was unable to replicate the observed SOC sequestration rate, probably because SOC stocks were not yet at equilibrium with litter inputs at the beginning of the monitoring period (contrary to our steady-state assumption). This explanation is also supported by the fact that the SOC sequestration rate decreased with stand age. As the SOC sequestration rate declines with stand age and is higher in uneven aged stands, forest management has the potential to influence this carbon sink. PMID- 27657986 TI - Genetics of gigantism and acromegaly. AB - Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly. PMID- 27657989 TI - Multi-faceted monitoring of estuarine turbidity and particulate matter provenance: Case study from Salem Harbor, USA. AB - Turbidity is a water quality parameter that is known to adversely affect aquatic systems, however the causes of turbid water are often elusive. We present results of a study designed to constrain the source of particulate matter in a coastal embayment that has suffered from increased turbidity over past decades. Our approach utilized monitoring buoys to quantify turbidity at high temporal resolution complemented by geochemical isotope analysis of suspended sediment samples and meteorological data. Results reveal a complex system in which multiple sources are associated with particulate matter. Weight of evidence demonstrates that phytoplankton productivity in the water column, however, is the dominant source of particulate matter associated with elevated turbidity in Salem Harbor, Massachusetts. Allochthonous matter from the watershed was observed to mix into the pool of suspended particulate matter near river mouths, especially in spring and summer. Resuspension of harbor surface sediments likely provides additional particulates in the regions of boat moorings, especially during summer when recreational boats are attached to moorings. Our approach allows us to constrain the causes of turbidity events in this embayment, is helping with conservation efforts of environmental quality in the region, and can be used as a template for other locations. PMID- 27657990 TI - Hydropeaking mitigation project on a multi-purpose hydro-scheme on Valsura River in South Tyrol/Italy. AB - A hydropeaking mitigation project on Valsura River in the Italians Alps is described. The project is of particular interest due to several aspects. First of all, the Valsura torrent has unique morphological braiding characteristics, which are unique in the reach of Adige valley between Merano and Bolzano, and has a good reproduction potential for fish, especially in the terminal stretch along a biotope before its confluence with Adige River. Moreover, the Valsura hydropower cascade, which overall consists of six high-head hydropower plants, has an exceptional economic importance for the local hydropower industry. Lastly, the last HPP on the cascade is a multipurpose plant, so that interesting interactions between hydropeaking mitigation, irrigation supply and peak energy production are considered. The project started from a hydrological and a limnological measuring campaign and from an energetic, hydraulic and legislative framework analysis. The ecological findings are combined into a deficit analysis, founding the basis for the definition of a hydrological target state, which points to achieve a good natural reproduction for brown trout in the hydropeaked stretch, fulfilling at the same time the human safety conditions. Finally, mitigation Measures are described that at the same time comply with the following manifold aspects: a. maintenance of the requested target limits for fish reproduction; b. maintenance of the water release for the agricultural irrigation; c. enhancement of the flexibility of the hydropower plant's operation; d. reduction of the risk for local population. The paper compares operational and constructive mitigation measures and shows that constructive hydropeaking mitigation measures, for the present case study, can combine the positive effects of ecological improvement with higher safety standards and more flexible energy production. PMID- 27657991 TI - Community-weighted mean of leaf traits and divergence of wood traits predict aboveground biomass in secondary subtropical forests. AB - Subtropical forests are globally important in providing ecological goods and services, but it is not clear whether functional diversity and composition can predict aboveground biomass in such forests. We hypothesized that high aboveground biomass is associated with high functional divergence (FDvar, i.e., niche complementarity) and community-weighted mean (CWM, i.e., mass ratio; communities dominated by a single plant strategy) of trait values. Structural equation modeling was employed to determine the direct and indirect effects of stand age and the residual effects of CWM and FDvar on aboveground biomass across 31 plots in secondary forests in subtropical China. The CWM model accounted for 78, 20, 6 and 2% of the variation in aboveground biomass, nitrogen concentration in young leaf, plant height and specific leaf area of young leaf, respectively. The FDvar model explained 74, 13, 7 and 0% of the variation in aboveground biomass, plant height, twig wood density and nitrogen concentration in young leaf, respectively. The variation in aboveground biomass, CWM of leaf nitrogen concentration and specific leaf area, and FDvar of plant height, twig wood density and nitrogen concentration in young leaf explained by the joint model was 86, 20, 13, 7, 2 and 0%, respectively. Stand age had a strong positive direct effect but low indirect positive effects on aboveground biomass. Aboveground biomass was negatively related to CWM of nitrogen concentration in young leaf, but positively related to CWM of specific leaf area of young leaf and plant height, and FDvar of plant height, twig wood density and nitrogen concentration in young leaf. Leaf and wood economics spectra are decoupled in regulating the functionality of forests, communities with diverse species but high nitrogen conservative and light acquisitive strategies result in high aboveground biomass, and hence, supporting both the mass ratio and niche complementarity hypotheses in secondary subtropical forests. PMID- 27657994 TI - Antioxidant Enzyme Activity and Cognition in Obese Individuals with or without Metabolic Risk Factors. AB - Background: The metabolic syndrome may be associated with cognitive impairment and increased oxidative stress. Aim: To document the association between metabolic syndrome, cognitive impairment and oxidative stress activity in metabolically healthy obese and in metabolically unhealthy obese individuals. Methods: 60 obese individuals aged (49+/-10 years, 52% male) were enrolled. Obesity was defined as BMI>30. Metabolic syndrome was defined according to ATP III guidelines. Obese individuals were divided into 2 groups: Group 1, metabolically healthy obese (<=2 components of metabolic syndrome), and Group 2, metabolically unhealthy obese (>2 components of metabolic syndrome). Cognitive dysfunction was determined by Montreal cognitive assessment score. Liver Fibro scan (Elastography), Inflammation (CRP), pro oxidants (MDA), antioxidant activity (SOD, PON, GSH, GPx) and insulin resistance (HOMA-IR) were measured. Results: Of the 30 metabolically unhealthy obese individuals, 13% developed dementia, 51% had mild cognitive impairment, and 36% had a normal cognitive score. In the metabolically healthy obese group, 3% developed dementia, 7% had mild cognitive impairment, and 90% had a normal cognitive score. There was a significant difference in liver stiffness (7+/-3 vs. 5.2+/-2.7 kpa, p<0.001), liver fat measurement (337+/-51 vs. 280+/-20 db/m, p<0.001), MDA (4.7+/-0.9 vs. 5.47+/-1.12 mM, P<0.003), Glutathione GSH (27.2+/-2.4 vs. 28.4+/-2.3, P<0.03), CRP (9+/-6 vs. 7+/-6 P<0.001) and insulin resistance (2.5+/-1 vs. 6+/-5.5 p<0.02) between the 2 groups. Correlations were significant between GPx activity and liver stiffness (r=0.37), GPx activity and abdominal girth (r=-0.22) and glucose concentration and SOD activity (r=0.4). Multivariate analysis showed that HOMA-IR, MDA and GSH were the most powerful predictors of metabolically unhealthy obesity. Conclusion: There is a significant mild cognitive impairment and increased oxidative stress activity in the metabolically unhealthy obese. Whether treatment with anti oxidants improves cognitive dysfunction remains to be determined. PMID- 27657992 TI - The population impact of human papillomavirus/cytology cervical cotesting at 3 year intervals: Reduced cervical cancer risk and decreased yield of precancer per screen. AB - BACKGROUND: The objective of cervical screening is to detect and treat precancer to prevent cervical cancer mortality and morbidity while minimizing overtreatment of benign human papillomavirus (HPV) infections and related minor abnormalities. HPV/cytology cotesting at extended 5-year intervals currently is a recommended screening strategy in the United States, but the interval extension is controversial. In the current study, the authors examined the impact of a decade of an alternative, 3-year cotesting, on rates of precancer and cancer at Kaiser Permanente Northern California. The effect on screening efficiency, defined as numbers of cotests/colposcopy visits needed to detect a precancer, also was considered. METHODS: Two cohorts were defined. The "open cohort" included all women screened at least once during the study period; > 1 million cotests were performed. In a fixed "long-term screening cohort," the authors considered the cumulative impact of repeated screening at 3-year intervals by restricting the cohort to women first cotested in 2003 through 2004 (ie, no women entering screening later were added to this group). RESULTS: Detection of cervical intraepithelial neoplasia 3/adenocarcinoma in situ (CIN3/AIS) increased in the open cohort (2004-2006: 82.0/100,000 women screened; 2007-2009: 140.6/100,000 women screened; and 2010-2012: 126.0/100,000 women screened); cancer diagnoses were unchanged. In the long-term screening cohort, the detection of CIN3/AIS increased and then decreased to the original level (2004-2006: 80.5/100,000 women screened; 2007-2009: 118.6/100,000 women screened; and 2010-2012: 84.9./100,000 women screened). The number of cancer diagnoses was found to decrease. When viewed in terms of screening efficiency, the number of colposcopies performed to detect a single case of CIN3/AIS increased in the cohort with repeat screening. CONCLUSIONS: Repeated cotesting at a 3-year interval eventually lowers population rates of precancer and cancer. However, a greater number of colposcopies are required to detect a single precancer. Cancer 2016;122:3682-6. (c) 2016 American Cancer Society. PMID- 27657995 TI - Effects of Streptozotocin-Induced Diabetes on Proliferation and Differentiation Abilities of Mesenchymal Stem Cells Derived from Subcutaneous and Visceral Adipose Tissues. AB - Introduction: Accumulated evidence indicates that there are intrinsic differences between adipose tissue-derived stem cells (ASCs) obtained from different body fat depots. Here, we compared the proliferation and multipotency of subcutaneous ASCs (SC-ASCs) and epididymal ASCs (ED-ASCs) before and after induction of diabetes by streptozotocin. Methods: The adipogenic and osteogenic abilities of rat SC-ASCs and ED-ASCs were evaluated using Oil Red O and Alizarin Red staining, respectively. The expression of adipocyte (PPAR-gamma, LPL) and osteoblast (ALP, SPP1) specific mRNAs was evaluated by quantitative real-time PCR. MTT test was used for determination of cell proliferation capacity. Results: The proliferation of SC-ASCs was higher than ED-ASCs, both before and after diabetes induction (P<0.05). Diabetes increased the proliferative capability of SC-ASCs (P<0.05) but not ED-ASCs. Before diabetes, both adipogenic and osteogenic differentiation of SC-ASCs were higher than ED-ASCs (P<0.05). After diabetes, both SC-ASCs and ED ASCs were able to differentiate into adipocyte and osteoblast, but the levels of differentiation were higher in SC-ASCs than in ED-ASCs (P<0.05). Diabetes decreased the expression of PPAR-gamma and LPL, but increased the SPP1 and ALP expression in both SC-ASCs and ED-ASCs. Conclusion: Our data suggested that diabetes increases the proliferation of ASCs but decreases their adipogenic differentiation. Also, SC-ASCs have higher proliferation and differentiation abilities than ED-ASCs in normal and diabetic conditions so can be more preferable for cell therapy. PMID- 27657996 TI - The Effect of Ezetimibe/Statin Combination and High-Dose Statin Therapy on Thyroid Autoimmunity in Women with Hashimoto's Thyroiditis and Cardiovascular Disease: A Pilot Study. AB - Background: Intensive statin therapy was found to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis. No similar data are available for other hypolipidemic agents. Methods: The participants of the study were 16 women with Hashimoto's thyroiditis and coronary artery disease. On the basis of statin tolerance, they were divided into 2 groups. 8 patients who did not tolerate high dose statin therapy were treated with a statin, the dose of which was reduced by half, together with ezetimibe. The remaining 8 patients tolerating the treatment continued high-dose statin therapy. Plasma lipids, serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: Replacing high-dose statin therapy with ezetimibe/statin combination therapy increased serum titers of thyroid peroxidase as well as led to an insignificant increase in serum titers of thyroglobulin antibodies. At the end of the study, thyroid peroxidase and thyroglobulin antibody titers were higher in patients receiving the combination therapy than in those treated only with high-dose statin. Conclusions: Our study shows that high-dose statin therapy produces a stronger effect on thyroid autoimmunity than ezetimibe/statin combination therapy. PMID- 27657997 TI - The Effect of Coenzyme Q10 Supplementation on Circulating Levels of Novel Adipokine Adipolin/CTRP12 in Overweight and Obese Patients with Type 2 Diabetes. AB - Background: Adipolin, the novel adipokine that is proposed to be reduced in diabetes, obesity and inflammation, may improve glycemic control. It is known that coenzyme Q10 could improve insulin sensitivity. The aim of the current study was to investigate the effect of Q10 supplementation on adipolin concentration and glucose metabolism in overweight and obese diabetic patients. Material & Methods: Sixty four patients with type 2 diabetes and 25200 residues. Butelase 1 is the fastest known ligase and is found in pods of the common medicinal plant Clitoria ternatea (also known as butterfly pea). It has a very simple C-terminal-specific recognition motif that requires Asn/Asp (Asx) at the P1 position and a dipeptide His-Val at the P1' and P2' positions. Substrates for butelase-mediated ligation can be prepared by standard Fmoc (9-fluorenylmethyloxycarbonyl) chemistry or recombinant expression with the minimal addition of this tripeptide Asn-His-Val motif at the C terminus. Butelase 1 achieves cyclizations that are 20,000 times faster than those of sortase A, a commonly used enzyme for backbone cyclization. Unlike sortase A, butelase is traceless, and it can be used for the total synthesis of naturally occurring peptides and proteins. Furthermore, butelase 1 is also useful for intermolecular ligations and synthesis of peptide or protein thioesters, which are versatile activated intermediates necessary for and compatible with many chemical ligation methods. The protocol describes steps for isolation and purification of butelase 1 from plant extract using a four-step chromatography procedure, which takes ~3 d. We then describe steps for intramolecular cyclization, intermolecular ligation and butelase-mediated synthesis of protein thioesters. Butelase reactions are generally completed within minutes and often achieve excellent yields. PMID- 27658014 TI - A composite critical-size rabbit mandibular defect for evaluation of craniofacial tissue regeneration. AB - Translational biomaterials targeted toward the regeneration of large bone defects in the mandible require a preclinical model that accurately recapitulates the regenerative challenges present in humans. Computational modeling and in vitro assays do not fully replicate the in vivo environment. Consequently, in vivo models can have specific applications such as those of the mandibular angle defect, which is used to investigate bone regeneration in a nonload-bearing area, and the inferior border mandibular defect, which is a model for composite bone and nerve regeneration, with both models avoiding involvement of soft tissue or teeth. In this protocol, we describe a reproducible load-bearing critical-size composite tissue defect comprising loss of soft tissue, bone and tooth in the mandible of a rabbit. We have previously used this procedure to investigate bone regeneration, vascularization and infection prevention in response to new biomaterial formulations for craniofacial tissue engineering applications. This surgical approach can be adapted to investigate models such as that of regeneration in the context of osteoporosis or irradiation. The procedure can be performed by researchers with basic surgical skills such as dissection and suturing. The procedure takes 1.5-2 h, with ~2 h of immediate postoperative care, and animals should be monitored daily for the remainder of the study. For bone tissue engineering applications, tissue collection typically occurs 12 weeks after surgery. In this protocol, we will present the necessary steps to ensure reproducibility; tips to minimize complications during and after surgery; and analytical techniques for assessing soft tissue, bone and vessel regeneration by gross evaluation, microcomputed tomography (microCT) and histology. PMID- 27658015 TI - Efficient genome engineering approaches for the short-lived African turquoise killifish. AB - A central challenge in experimental aging research is the lack of short-lived vertebrate models for genetic studies. Here we present a comprehensive protocol for efficient genome engineering in the African turquoise killifish (Nothobranchius furzeri), which is the shortest-lived vertebrate in captivity with a median life span of 4-6 months. By taking advantage of the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) system and the turquoise killifish genome, this platform enables the generation of knockout alleles via nonhomologous end joining (NHEJ) and knock-in alleles via homology-directed repair (HDR). We include guidelines for guide RNA (gRNA) target design, embryo injection and hatching, germ-line transmission and for minimizing off-target effects. We also provide strategies for Tol2-based transgenesis and large-scale husbandry conditions that are critical for success. Because of the fast life cycle of the turquoise killifish, stable lines can be generated as rapidly as 2-3 months, which is much faster than other fish models. This protocol provides powerful genetic tools for studying vertebrate aging and aging-related diseases. PMID- 27658016 TI - Synthesis, lipid membrane incorporation, and ion permeability testing of carbon nanotube porins. AB - Carbon nanotube porins (CNTPs) are 10- to 20-nm-long segments of lipid-stabilized single-walled carbon nanotubes (CNTs) that can be inserted into phospholipid membranes to form nanometer-scale-diameter pores that approximate the geometry and many key transport characteristics of biological membrane channels. We describe protocols for CNTP synthesis by ultrasound-assisted cutting of long CNTs in the presence of lipid amphiphiles, and for validation of CNTP incorporation into a lipid membrane using a proton permeability assay. In addition, we describe protocols for measuring conductance of individual CNTPs in planar lipid bilayers and plasma membranes of live cells. The protocol for the preparation and testing of the CNTPs in vesicle systems takes 3 d, and single CNTP conductance measurements take 2-5 h. The CNTPs produced by this cutting protocol remain stable and active for at least 10-12 weeks. PMID- 27658017 TI - Saccharide Recognition Based on Self-Assembly of Amphiphilic Phenylboronic Acid Azoprobes. AB - We designed amphiphilic phenylboronic acid azoprobes (B-Azo-Cn) and evaluated their saccharide recognition function in relation to the micelle formation changes of the self-assembled B-Azo-Cn. First, we evaluated B-Azo-C8 in a 1% methanol-99% water solution under basic conditions. The wavelength of maximum absorption in the ultraviolet-visible (UV-vis) spectra of B-Azo-C8 was shifted, and the solution showed a color change with the addition of saccharides. The morphology of B-Azo-C8 was evaluated using dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM) observations. B-Azo-C8 formed aggregates in the absence of saccharides and in the presence of glucose. In the presence of fructose, micelle-formed B-Azo-C8 was dispersed, indicating that B-Azo-C8 changed its dispersion state by recognizing fructose. The effect of alkyl chain length on the saccharide recognition ability was examined as well. B Azo-C4 and B-Azo-C12 did not recognize saccharides in a 1% methanol-99% water solution under basic conditions, indicating that an appropriate alkyl chain length was required for recognizing saccharides. The control of the hydrophilic lipophilic balance (HLB) was a key factor for saccharide recognition. PMID- 27658019 TI - Thermal Decomposition of 2-Pentanol: A Shock Tube Study and RRKM Calculations. AB - A single pulse shock tube was used to study the thermal decomposition of 2 pentanol in the temperatures between 1110 and 1325 K. Three major decomposition products are methane, ethylene, and propylene. The minor products detected in lower concentration are ethane, acetylene, acetaldehyde, 1-pentene, and 2 pentene. The rate coefficient for the overall decomposition of 2-pentanol was found to be ktotalexp(1110-1325 K) = (4.01 +/- 0.51) * 109 exp(-(36.2 +/- 4.7)/RT) s-1, where the activation energies are given in kcal mol-1. To simulate reactant and product distribution over the experimentally studied temperatures between 1110 and 1325 K, a reaction scheme was constructed with 34 species and 39 reactions. In addition to this, the temperature and pressure dependent rate coefficients were computed for various unimolecular dissociation pathways using RRKM theory. The high pressure limit rate coefficient for overall decomposition of 2-pentanol was obtained to be ktotaltheory(500-2500 K) = (9.67 +/- 1.11) * 1014 exp(-(67.7 +/- 2.9)/RT) s-1. The calculated high pressure rate coefficients and experimentally measured rate constants are in good agreement with each other. The reaction is primarily governed by the unimolecular elimination of water. PMID- 27658018 TI - HIV-related stigma and discrimination in the New Zealand healthcare setting: a mixed-methods study. AB - : Background People living with HIV (PLHIV) assume that healthcare workers have an adequate knowledge of HIV and expect that they will be treated with respect and compassion in the healthcare setting. Despite the remarkable advances in HIV treatment in the past two decades, PLHIV have continued to experience HIV-related stigma and discrimination by healthcare workers worldwide. The aim of this study was to explore the prevalence and nature of stigma and discrimination experienced by PLHIV in the healthcare setting in New Zealand. METHODS: This study involved a mixed-methods approach, using a questionnaire to collect quantitative and qualitative data from PLHIV recruited from the HIV Clinic at Auckland City Hospital and from two national HIV peer-support organisations between August 2012 and February 2013. RESULTS: Two hundred and thirteen PLHIV participated in the study. One hundred PLHIV (47%) reported that they had ever experienced HIV related discrimination by a healthcare worker. The types of discrimination included confidentiality problems (19%), additional infection control measures (19%) and rudeness (18%). Healthcare settings where most of the discrimination had been experienced were other (non-infectious diseases) hospital wards, dental clinics, other (non-HIV) outpatient clinics and general practice clinics. CONCLUSION: Almost half of the PLHIV in New Zealand have experienced stigma and discrimination in a healthcare setting. The findings of this study show that there is a need to continue to normalise the care of HIV and increase HIV education for healthcare workers. PMID- 27658020 TI - Effect of Weakening of Ipsilateral Depressor Anguli Oris on Smile Symmetry in Postparalysis Facial Palsy. AB - Importance: Aberrant depressor anguli oris (DAO) activity may arise after recovery from acute facial paralysis and restrict movement of the oral commissure. Objective: To quantify the degree to which DAO inhibition affects smile dynamics and perceived emotional state. Design, Setting, and Participants: In this prospective, pretest-posttest study performed at an academic tertiary referral hospital, patients with unilateral postparalysis facial palsy were studied from January 16 through April 30, 2016. Interventions: Local anesthetic injection into the ipsilateral DAO. Main Outcomes and Measures: Healthy- and paretic-side commissure displacements from the midline lower vermillion border referenced to the horizontal plane were calculated from random-ordered photographs of full-effort smile before and after injection, and random-ordered hemifacial photographs of the paretic side were assessed as expressing positive, negative, or indiscernible emotion. Results: Twenty patients were identified as having unilateral postparalysis facial palsy with marked synkinesis of the ipsilateral DAO. Patient mean age was 46 years (range, 24-67 years), with a male to female ratio of 1:3. Mean paretic-side commissure displacement increased from 27.45 mm at 21.65 degrees above the horizontal plane to 29.35 mm at 23.58 degrees after DAO weakening (mean difference, 1.90 mm; 95% CI, 1.26-2.54 mm; and 1.93 degrees ; 95% CI, 0.34 degrees -3.51 degrees ; P < .001 and P = .20, respectively). Symmetry of excursion between sides improved by 2.00 mm (95% CI, 1.16-2.83 mm; P < .001) and 2.71 degrees (95% CI, 1.38 degrees -4.03 degrees ; P < .001). At baseline, observers assessed 7 of 20 paretic hemifaces (35%) as expressing positive emotion; this proportion increased to 13 of 20 (65%) after DAO weakening (P = .03). Conclusions and Relevance: Ipsilateral DAO weakening results in significant improvements in smile dynamics and perceived expression of positive emotion on the paretic hemiface in postparalysis facial palsy. A trial of DAO weakening should be offered to patients with this disfiguring complication of Bell palsy and similar facial nerve insults. Level of Evidence: 3. PMID- 27658021 TI - Invasive Fungal Disease in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant. AB - Invasive fungal disease (IFD) remains a major cause of morbidity and mortality in pediatric patients after allogeneic hematopoietic stem cell transplant (HSCT). We analyzed the outcome of 152 consecutive pediatric patients who underwent allogeneic HSCT from 2005 to 2012: 126 of these without a history of IFD and 26 with IFD before HSCT. Antifungal prophylaxis agent was determined by the primary transplant attending. The rate of IFD after HSCT among patients with or without prior IFD was similar (7.7% with and 7.1% without a history of fungal disease before transplant). Mortality in these 2 populations did not differ (35% vs. 28%, P=0.48, chi). Patients deemed at higher risk for IFD were generally placed on voriconazole prophylaxis; however, this did not affect rates of posttransplant IFD. All-cause mortality in patients with posttransplant IFD was significantly higher than those without posttransplant IFD (67% vs. 21%, P<0.0001,chi). Identifying risk factors for posttransplant IFD remains a high priority to improve outcome of HSCT. PMID- 27658022 TI - Eukaryotic transcription initiation machinery visualized at molecular level. AB - The structures of RNA Polymerase (Pol) II pre-initiation complexes (PIC) have recently been determined at near-atomic resolution, elucidating unprecedented mechanistic details of promoter opening during transcription initiation. The key structural features of promoter opening are summarized here. Structural knowledge of Pol I and III PIC is also briefly discussed. PMID- 27658024 TI - Mechanism of action of allergen immunotherapy. AB - BACKGROUND: Allergen immunotherapy (AIT) leads to the production of antiallergen immunoglobulin (IgG) or "blocking antibody" in the serum and an increase in antiallergen IgG and IgA in nasal secretions. There is also a decrease in the usual rise in antiallergen IgE that occurs after the pollen season. METHODS: In this paper, mechanisms of action of allergen immunotherapy is reviewed. RESULTS: Regulatory T (Treg) cells and their cytokines, primarily interleukin (IL) 10 and transforming growth factor beta, suppress T-helper type 2 immune responses and control allergic diseases in many ways. AIT induces a shift in the proportion of IL-4-secreting T-helper type 2 cells in favor of IL-10-secreting inducible Treg cells specific for the same allergenic epitope that increases in number and function. Different types of inducible Treg control several facets of allergic inflammation. There are two main types of immunotherapy: subcutaneous immunotherapy and sublingual immunotherapy. Subcutaneous immunotherapy is efficacious and is indicated for the reduction of seasonal symptoms. Sublingual immunotherapy involves the regular self-administration and retention of allergen extract under the tongue for 1-2 minutes before the extract is swallowed. The allergens cross the mucosa in 15-30 minutes and are then captured by tolerogenic dendritic cells and processed as small peptides. Next, via the lymphatic system, a systemic immune response is created to produce an early decrease in mast cell and basophil degranulation. CONCLUSION: AIT is indicated for the treatment of moderate-to-severe intermittent or persistent symptoms of allergic rhinitis. AIT can be administered to those >5 years of age and has been shown to be safe in children as young as 3 years of age. In this article, AIT and other types of immunotherapies were discussed as well as the indications for immunotherapy. PMID- 27658025 TI - Clinical efficacy of immunotherapy in allergic rhinitis. AB - BACKGROUND: Aeroallergen immunotherapy (AIT) should be considered for patients who exhibit symptoms of allergic rhinitis (AR), rhinoconjunctivitis, and/or asthma after natural exposure to allergens and who also demonstrate specific immunoglobulin E antibodies against relevant allergens. METHODS: In this paper, clinical efficacy of immunotherapy in allergic rhinitis is reviewed. RESULT: Subcutaneous allergen immunotherapy (SCIT) is effective for seasonal and perennial AR. Sustained effectiveness requires several years of treatment. SCIT may prevent the development of allergic asthma in children with AR. Sublingual allergen immunotherapy (SLIT) is currently considered an alternative treatment to the subcutaneous route. The use of SLIT has been included in international guidelines for the treatment of AR with or without conjunctivitis. CONCLUSION: Patients treated with SCIT are at risk of both local and systemic adverse reactions; however, in most cases, symptoms are readily reversible if they are recognized early and treated promptly. The safety profile of SLIT is good; therefore, SLIT can be self-administered by patients in their homes. In this article, we reviewed the efficacy and safety of allergen immunotherapy. PMID- 27658023 TI - Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. AB - MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria. PMID- 27658026 TI - Alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy. AB - BACKGROUND: Some alternative products instead of immunotherapy are used in patients with allergic rhinitis (AR). METHODS: In this paper, alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy are reviewed. RESULTS: Alternative products and methods used instead of immunotherapy are tea therapy, acupuncture, Nigella sativa, cinnamon bark, Spanish needle, acerola, capsaicin (Capsicum annum), allergen-absorbing ointment, and cellulose powder. N. sativa has been used in AR treatment due to its anti-inflammatory effects. N. sativa oil also inhibits the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism. The beneficial effects of N. sativa seed supplementation on the symptoms of AR may be due to its antihistaminic properties. To improve the efficacy of immunotherapy, some measures are taken regarding known immunotherapy applications and alternative routes of intralymphatic immunotherapy and epicutaneous immunotherapy are used. CONCLUSION: There are alternative routes and products to improve the efficacy of immunotherapy. PMID- 27658027 TI - The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis. AB - Chlamydia trachomatis is an obligate intracellular pathogen that requires specific essential nutrients from the host cell, one of which is the amino acid tryptophan. In this context interferon gamma (IFNgamma) is the major host protective cytokine against chlamydial infections because it induces the expression of the host enzyme, indoleamine 2,3-dioxygenase 1, that degrades tryptophan, thereby restricting bacterial replication. The mechanism by which IFNgamma acts has been dissected in vitro using epithelial cell-lines such as HeLa, HEp-2, or the primary-like endocervical cell-line A2EN. All these cell lines express the high-risk human papillomavirus oncogenes E6 & E7. While screening cell-lines to identify those suitable for C. trachomatis co-infections with other genital pathogens, we unexpectedly found that tryptophan starvation did not completely block chlamydial development in cell-lines that were HR-HPV negative, such as C33A and 293. Therefore, we tested the hypothesis that HR-HPV oncogenes modulate the effect of tryptophan starvation on chlamydial development by comparing chlamydial development in HeLa and C33A cell-lines that were both derived from cervical carcinomas. Our results indicate that during tryptophan depletion, unlike HeLa, C33A cells generate sufficient intracellular tryptophan via proteasomal activity to permit C. trachomatis replication. By generating stable derivatives of C33A that expressed HPV16 E6, E7 or E6 & E7, we found that E6 expression alone was sufficient to convert C33A cells to behave like HeLa during tryptophan starvation. The reduced tryptophan levels in HeLa cells have a biological consequence; akin to the previously described effect of IFNgamma, tryptophan starvation protects C. trachomatis from clearance by doxycycline in HeLa but not C33A cells. Curiously, when compared to the known Homo sapiens proteome, the representation of tryptophan in the HR-HPV E6 & E6AP degradome is substantially lower, possibly providing a mechanism that underlies the lowered intracellular free tryptophan levels in E6-expressing cells during starvation. PMID- 27658028 TI - Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency. AB - INTRODUCTION: Phosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI. METHODS: Forty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography). RESULTS: Sevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p<0.05 for all versus Sham), while sevelamer increased bone mineral density (+2%) and prevented the deleterious changes in bone. In the femoral neck, CRI reduced bone mineral density (-11%) and breaking load (-10%), while sevelamer prevented the decrease in bone mineral density (+6%) so that breaking load did not differ from controls. CONCLUSIONS: In this model of stage 3-4 CRI, sevelamer-HCl treatment ameliorated the decreases in femoral midshaft and neck mineral density, and restored bone strength despite prevailing acidosis. Therefore, treatment with sevelamer can efficiently preserve mechanical competence of bone in CRI. PMID- 27658029 TI - Zhongdanyaozhi No. 1 and Zhongdanyaozhi No. 2 Are Hybrid Cultivars of Salvia miltiorrhiza with High Yield and Active Compounds Content. AB - Salvia miltiorrhiza Bunge is an important medicinal plant used for the treatment of cardiovascular disease. Intraspecific hybridization between a male sterile line and inbred lines was followed by 39 F1 crossings. Cultivars "Zhongdanyaozhi No. 1" (ZD1) and "Zhongdanyaozhi No. 2" (ZD2) were obtained. In 2012 and 2013 tests in Beijing, the two cultivars were compared with three widely accepted types, SDCK, SXCK and HNCK from Shandong, Shanxi and Henan provinces. The yield of ZD1 and ZD2 exceeded the three CKs by more than 48.2% and 39.2%, respectively; the composition of the two hybrid cultivars was similar to the control, although the content of some compounds varied to some extent. The content of salvianolic acid B and tanshinone II A of both ZD1 and ZD2 could measure up the requirement of Chinese Pharmacopoeia. The former showed no obvious advantage than the three CKs, while the later's tanshinone II A was 29.6% higher than the three CKs. Taken together, ZD1 is a high yielding and thick-root-type cultivar which is suitable for decoction pieces; while ZD2 is suitable for component especially lipophilic component extraction. ZD1 and ZD2 reported here are the first cultivars obtained by the hybridization of S. miltiorrhiza. PMID- 27658030 TI - SpyTag/SpyCatcher Cyclization Enhances the Thermostability of Firefly Luciferase. AB - SpyTag can spontaneously form a covalent isopeptide bond with its protein partner SpyCatcher. Firefly luciferase from Photinus pyralis was cyclized in vivo by fusing SpyCatcher at the N terminus and SpyTag at the C terminus. Circular LUC was more thermostable and alkali-tolerant than the wild type, without compromising the specific activity. Structural analysis indicated that the cyclized LUC increased the thermodynamic stability of the structure and remained more properly folded at high temperatures when compared with the wild type. We also prepared an N-terminally and C-terminally shortened form of the SpyCatcher protein and cyclization using this truncated form led to even more thermostability than the original form. Our findings suggest that cyclization with SpyTag and SpyCatcher is a promising and effective strategy to enhance thermostability of enzymes. PMID- 27658031 TI - Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: 'The Co-MED Study'. AB - OBJECTIVE: Hyponatraemia is common and its differential diagnosis is challenging. Commonly used diagnostic algorithms have limited diagnostic accuracy. Copeptin, the c-terminal portion of the precursor peptide of arginine vasopressin might help in the differential diagnosis of hyponatraemia. DESIGN: Prospective multicentre observational study. PATIENTS/METHODS: A total of 298 patients admitted with profound hypoosmolar hyponatraemia (Na < 125 mmol/l) were evaluated. Three experts uninvolved in the patients' care determined the aetiology of hyponatraemia after standardized diagnostic evaluation. RESULTS: Hyponatraemia differential diagnoses were as follows: syndrome of inappropriate antidiuresis (SIAD), 106 patients (35.6%); 'diuretic-induced', 72 (24.2%); 'hypovolaemic', 59 (19.8%); 'hypervolaemic', 33 (11.1%); primary polydipsia (PP), 24 (8.1%); and cortisol deficiency, 4 (1.3%). Copeptin levels <3.9 pmol/l identified patients with PP with high specificity (91%). Further, copeptin levels >84 pmol/l were highly predictive for hypovolaemic hyponatraemia (specificity: 90%). Urinary sodium levels and copeptin/urinary sodium ratio in patients with SIAD were higher and lower as compared to other hyponatraemia aetiologies (P < 0.0001). However, the specificity to identify SIAD was moderate for both parameters (31% and 61%). Fractional uric acid excretion (FEUA ) and fractional urea excretion (FEurea ) were higher in patients with SIAD compared to other hyponatraemia aetiologies (both P < 0.0001). FEurea values >55% and FEUA values >12% had a specificity of 96% and 77% to detect patients with SIAD. These results remained similar after excluding patients taking diuretics. CONCLUSIONS: Overall, there is only limited diagnostic utility of copeptin in the differential diagnosis of profound hyponatraemia. Very low copeptin levels are seen in patients with PP and highest copeptin levels in hypovolaemic hyponatraemia. To discriminate between SIAD and other hyponatraemia aetiologies, FEurea and FEUA levels are valuable irrespective of diuretics use. PMID- 27658032 TI - Transverse patterning, aging, and neuropsychological correlates in humans. AB - Transverse patterning is a learning and memory adaptation of the 'rock/paper/scissors' problem that has been though to depend on the hippocampus, is sensitive to aging, and requires pattern separation to solve. Previous investigators dichotomized cognitively normal older adults who passed a cognitive screening into impaired and unimpaired subsets, and found that impaired older adults were disproportionately deficient in pattern separation abilities. However, this variability in pattern separation ability has not been examined using a transverse patterning task. Our aims, then, were two-fold: First, to determine if impaired older adults were inferior on transverse patterning compared to unimpaired older adults and young adults; second, to identify the neuropsychological correlates of transverse patterning. Our findings revealed that impaired older adults required more trials to criterion on the transverse patterning task than both young adults and unimpaired older adults. Unimpaired older adults also required more trials to criterion than young adults. A detailed analysis of the transverse patterning task confirmed that the aforementioned group differences were only observed in high interference conditions when pattern separation demands were at their peak. Finally, regression analyses showed that both memory and executive functioning neuropsychological composite scores were related to different indices of transverse patterning performance. Consistent with the pattern separation literature, and despite passing a cognitive screening, we found disproportionate transverse patterning deficits in impaired older adults. Forthcoming work should determine if transverse patterning performance is similar between impaired older adults and patients with Mild Cognitive Impairment. (c) 2016 Wiley Periodicals, Inc. PMID- 27658033 TI - Comparison of Physiological Parameters and Anaesthesia Specific Observations during Isoflurane, Ketamine-Xylazine or Medetomidine-Midazolam-Fentanyl Anaesthesia in Male Guinea Pigs. AB - Guinea pigs (GPs) are difficult to anaesthetize successfully, the choices for anaesthesia are limited and physiological parameters are likely to be influenced substantially under anaesthesia. We implanted blood pressure radio-telemetry devices into 16 male GPs and subjected them to anaesthesia with ketamine-xylazine (KX), medetomidine-midazolam-fentanyl (MMF) or isoflurane (Iso, plus atropine premedication) in a randomized order with a 7 day interval between anaesthesias. Each anaesthesia lasted 40min, after which Iso was discontinued, MMF was fully antagonized with atipamezole-flumazenil-naloxone and KX was partially antagonized with atipamezole. Hemodynamics were recorded continuously for at least 240min after induction and the GPs were monitored for respiratory rate, reflex responses and specific observations until regaining of their righting reflex (RR). Blood for glucose testing was taken from the ear at 7.5, 20 and 40min during anaesthesia. Recovery time was short with MMF and Iso but long for KX. MMF induced only a transient blood pressure drop after antagonization, whereas Iso caused a marked hypotension during maintenance and KX led to moderate hypotension after antagonization. MMF and Iso produced tolerable heart rate changes, but KX led to long term post-anaesthetic bradycardia. Hypothermia occurred with all anaesthesias, but the GPs returned to normothermia the fastest under MMF, followed shortly by Iso. KX, however, caused a profound and prolonged hypothermia. The respiration was depressed with all anaesthesias, substantially with MMF (-41%) and KX (-52%) and severe during Iso maintenance (-71%). Blood glucose with MMF and KX increased throughout the anaesthesia, but the values remained within reference values with all anaesthetics. The reflex responses character and strength varied between the anaesthetics. In conclusion, MMF is the anaesthetic of choice and Iso may be used for short, non-painful procedures. We advise against the use of KX in GPs. PMID- 27658039 TI - Heptose Sounds the Alarm: Innate Sensing of a Bacterial Sugar Stimulates Immunity. PMID- 27658040 TI - Vimentin filament controls integrin alpha5beta1-mediated cell adhesion by binding to integrin through its Ser38 residue. AB - Regulation of integrin affinity for its ligand is essential for cell adhesion and migration. Here, we found that direct interaction of vimentin with integrin beta1 can enhance binding of integrin alpha5beta1 to its ligand, fibronectin. Conversely, blocking the interaction reduced fibronectin binding, cell migration on a fibronectin-coated surface, and neural tube closure during Xenopus embryogenesis. We also found that withaferin A (WFA), a natural compound known to inhibit vimentin function, can suppress the vimentin-integrin interaction and abolish fibronectin binding. Finally, we identified Ser38 of vimentin as a critical residue for integrin binding. Our results suggest that phosphorylation of vimentin at Ser38 may regulate the integrin-ligand interaction, thus providing a molecular basis for antivimentin therapeutic strategies. PMID- 27658041 TI - Self-Reported Sitting Time, Physical Activity and Fibrinolytic and Other Novel Cardio-Metabolic Biomarkers in Active Swedish Seniors. AB - BACKGROUND: Too much sitting is linked with an increased risk of cardiovascular disease and mortality. The mediating mechanisms for these associations are largely unknown, however dysregulated fibrinolysis have emerged as a possible contributor. OBJECTIVE: We examined the associations of self-reported overall sitting time and physical activity with fibrinolytic and other novel cardio metabolic biomarkers in older adults. MATERIALS AND METHODS: Data was analysed for 364 participants (74+/-7 yrs) of the Active Seniors group (retired, living independently in their own homes). Linear regression analyses examined associations of categories of categories of sitting time (<=3, 3-6, >6 hrs/day) and overall physical activity (Low, Moderate and High) with biomarkers in serum or plasma, adjusting for age, gender and smoking (with further adjustment for either overall physical activity or sitting time and BMI in secondary analyses). RESULTS: Compared to sitting <= 3 hrs/day, sitting >6 hrs/day was associated with higher tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex). These associations were not independent of overall physical activity or BMI. Compared to those in the high physical activity, low physical activity was associated with a higher BMI, high-sensitivity C-reactive protein (hs-CRP) and tPA-PAI-1 complex levels. Only the associations of BMI and hs-CRP were independent of sitting time. CONCLUSIONS: These findings provide preliminary cross-sectional evidence for the relationships of sitting time with fibrinolytic markers in older adults. They also reinforce the importance of regular physical activity for cardio-metabolic health. PMID- 27658042 TI - Identifying Leprosy and Those at Risk of Developing Leprosy by Detection of Antibodies against LID-1 and LID-NDO. AB - Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. Challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. Although phenolic glycolipid (PGL)-I has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. The aim of this study was to evaluate the effectiveness of two related reagents, LID-1 and LID-NDO, for the detection of M. leprae infection. Sera from 98 leprosy patients, 365 household contacts (HHC) and 98 endemic controls from Rio Grande do Norte, Brazil, were evaluated. A subgroup of the HHC living in a hyperendemic area was followed for 7-10 years. Antigen-specific antibody responses were highest in multibacillary (MB) at the lepromatous pole (LL/BL) and lowest in paucibacillary (PB) at the tuberculoid pole (TT/BT). A positive correlation for both anti-LID-1 and anti-LID-NDO antibodies was found with bacterial burden (LID-1, r = 0.84, p<0.001; LID-NDO, r = 0.82, p<0.001), with higher sensitivity than bacilloscopy. According to Receiver Operating Curve, LID 1 and LID-NDO performed similarly. The sensitivity for MB cases was 89% for LID-1 and 95% for LID-NDO; the specificity was 96% for LID-1 and 88% for LID-NDO. Of the 332 HHC that were followed, 12 (3.6%) were diagnosed with leprosy in a median time of 31 (3-79) months after recruitment. A linear generalized model using LID 1 or LID-NDO as a predictor estimated that 8.3% and 10.4% of the HHC would become a leprosy case, respectively. Together, our findings support a role for the LID-1 and LID-NDO antigens in diagnosing MB leprosy and identifying people at greater risk of developing clinical disease. These assays have the potential to improve the diagnostic capacity at local health centers and aid development of strategies for the eventual control and elimination of leprosy from endemic areas. PMID- 27658043 TI - Insulin-Like Growth Factor I (IGF-I) Expressed from an AAV1 Vector Leads to a Complete Reversion of Liver Cirrhosis in Rats. AB - IGF-I modulates liver tissue homeostasis. It is produced by hepatocytes and signals within the liver through IGF-I receptor expressed on hepatic stellate cells (HSCs). Liver cirrhosis is characterized by marked IGF-I deficiency. Here we compared the effect of two different gene therapy vectors encoding IGF-I as a potential treatment for cirrhotic patients. Rats with carbon tetrachloride induced liver cirrhosis were treated with controls or with adeno-associated virus 1 (AAV) or simian virus 40 (SV40) vectors expressing IGF-I (AAVIGF-I or SVIGF-I) and molecular and histological studies were performed at 4 days, 8 weeks and 16 weeks. Increased levels of IGF-I were observed in the liver as soon as 4 days after vector administration. Control cirrhotic rats showed increased hepatic expression of pro-inflammatory and pro-fibrogenic factors including transforming growth factor beta (TGFbeta), tumor necrosis factor-alpha (TNFalpha), connective tissue growth factor (CTGF), and vascular endothelial growth factor (VEGF) together with upregulation of alpha-smooth muscle actin (alphaSMA), a marker of HSC activation. In IGF-I-treated rats the levels of all these molecules were similar to those of healthy controls by week 8 post-therapy. Of note, the decline of TGFbeta, CTGF, VEGF and alphaSMA expression was more rapid in AAVIGF-I treated animals reaching statistical significance by day 4 post-therapy. IGF-I-treated rats showed similar improvement of liver function tests in parallel with upregulation of hepatocyte nuclear factor 4alpha (HNF4alpha), a factor that promotes hepatocellular differentiation. A significant decrease of liver fibrosis, accompanied by upregulation of the hepatoprotective and anti-fibrogenic hepatocyte growth factor (HGF), occurred in all IGF-I-treated rats but complete reversal of liver cirrhosis took place only in AAVIGF-I group. Therefore, AAVIGF I reverts liver cirrhosis in rats, a capability which deserves clinical testing. PMID- 27658044 TI - The First Complete Plastid Genome from Joinvilleaceae (J. ascendens; Poales) Shows Unique and Unpredicted Rearrangements. AB - Joinvilleaceae is a family of tropical grass-like monocots that comprises only the genus Joinvillea. Previous studies have placed Joinvilleaceae in close phylogenetic proximity to the well-studied grass family. A full plastome sequence was determined and characterized for J. ascendens. The plastome was sequenced with next generation methods, fully assembled de novo and annotated. The assembly revealed two novel inversions specific to the Joinvilleaceae lineage and at least one novel plastid inversion in the Joinvilleaceae-Poaceae lineage. Two previously documented inversions in the Joinvilleaceae-Poaceae lineage and one previously documented inversion in the Poaceae lineage were also verified. Inversion events were identified visually and verified computationally by simulation mutations. Additionally, the loss and subsequent degradation of the accD gene in order Poales was explored extensively in Poaceae and J. ascendens. The two novel inversions along with changes in gene composition between families better delimited lineages in the Poales. The presence of large inversions and subsequent reversals in this small family suggested a high potential for large-scale rearrangements to occur in plastid genomes. PMID- 27658045 TI - Antisense Oligonucleotides Modulating Activation of a Nonsense-Mediated RNA Decay Switch Exon in the ATM Gene. AB - ATM (ataxia-telangiectasia, mutated) is an important cancer susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. ATM mutations in the germ line result in ataxia-telangiectasia (A-T), a rare genetic syndrome associated with hypersensitivity to double-strand DNA breaks and predisposition to lymphoid malignancies. ATM expression is limited by a tightly regulated nonsense-mediated RNA decay (NMD) switch exon (termed NSE) located in intron 28. In this study, we identify antisense oligonucleotides that modulate NSE inclusion in mature transcripts by systematically targeting the entire 3.1-kb long intron. Their identification was assisted by a segmental deletion analysis of transposed elements, revealing NSE repression upon removal of a distant antisense Alu and NSE activation upon elimination of a long terminal repeat transposon MER51A. Efficient NSE repression was achieved by delivering optimized splice-switching oligonucleotides to embryonic and lymphoblastoid cells using chitosan-based nanoparticles. Together, these results provide a basis for possible sequence-specific radiosensitization of cancer cells, highlight the power of intronic antisense oligonucleotides to modify gene expression, and demonstrate transposon-mediated regulation of NSEs. PMID- 27658046 TI - CD4+ Recent Thymic Emigrants Are Recruited into Granulomas during Leishmania donovani Infection but Have Limited Capacity for Cytokine Production. AB - Recent thymic emigrants (RTEs) represent a source of antigen-naive T cells that enter the periphery throughout life. However, whether RTEs contribute to the control of chronic parasitic infection and how their potential might be harnessed by therapeutic intervention is currently unclear. Here, we show that CD4+ recent thymic emigrants emerging into the periphery of mice with ongoing Leishmania donovani infection undergo partial activation and are recruited to sites of granulomatous inflammation. However, CD4+ RTEs displayed severely restricted differentiation either into IFNgamma+ or IFNgamma+TNFalpha+ effectors, or into IL 10-producing regulatory T cells. Effector cell differentiation in the chronically infected host was not promoted by adoptive transfer of activated dendritic cells or by allowing extended periods of post-thymic differentiation in the periphery. Nevertheless, CD4+ RTEs from infected mice retained the capacity to transfer protection into lymphopenic RAG2-/- mice. Taken together, our data indicate that RTEs emerging into a chronically inflamed environment are not recruited into the effector pool, but retain the capacity for subsequent differentiation into host protective T cells when placed in a disease-free environment. PMID- 27658047 TI - A Rationally Designed TNF-alpha Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice. AB - The TNF-alpha biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti drug antibody responses. Attempts to develop anti-TNF-alpha vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-alpha epitope scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF alpha epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-alpha, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases. PMID- 27658048 TI - IL-1beta maintains the redox balance by regulating glutaredoxin 1 expression during oral carcinogenesis. AB - BACKGROUND: Interleukin-1 beta (IL-1beta) is a pleiotropic cancer-inflammation linked cytokine which has been reported upregulated in many cancers. In our previous study, IL-1beta was found to be one of the key node genes during oral malignant transformation, and glutaredoxin 1 (Grx1) was identified as one of the downstream genes of IL-1beta in tumor microenvironment. Grx1 is ubiquitous oxidoreductase which is necessary for scavenging reactive oxygen species (ROS) and the intracellular redox balance maintenance. METHODS: Tissues from different stages of mucosal malignant transformation were obtained from 4NQO-induced rat oral carcinogenesis model and human mucosa for Grx1 expression detection by immunohistochemical staining. The intracellular ROS levels and Grx1 mRNA level of oral squamous carcinoma cell CAL27 were detected after IL-1beta treatment with or without pretreatment of IL-1Ra or NAC, respectively. The ROS levels were detected in Leti-si-IL-1beta and Leti-si-NC CAL27 cells after IL-1beta stimulation. The invasion and migration abilities of CAL27 cells were tested by transwell assay after IL-1beta stimulation with or without pretreatment of IL-1Ra. RESULTS: Grx1 expression was associated with the malignant transformation process in vivo. Exogenous IL-1beta upregulated the intracellular ROS level and the expression of Grx1 in CAL27 cells, which could be counteracted by IL-1Ra. The intracellular ROS accumulation induced by exogenous IL-1beta was responsible for the Grx1 upregulation. Endogenous IL-1beta acted as a switch in regulating the ROS level by modulating Grx1 expression, which was involved in the invasion and migration of OSCC cells. CONCLUSIONS: IL-1beta finely orchestrated the redox balance during carcinogenesis by modulating Grx1 expression. PMID- 27658050 TI - Price comparison of high-cost originator medicines in European countries. AB - BACKGROUND: In recent years, high-cost medicines have increasingly been challenging the public health budget in all countries including high-income economies. In this context, this study aims to survey, analyze and compare prices of medicines that likely contribute to high expenditure for the public payers in high-income countries. METHODS: We chose the following 16 European countries: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, the Netherlands, Portugal, Sweden, Slovakia, Spain and United Kingdom. The ex-factory price data of 30 medicines in these countries were collected in national databases accessible through the Pharmaceutical Price Information (PPI) service of Gesundheit Osterreich GmbH (Austrian Public Health Institute). RESULTS: The ex-factory prices (median) per unit (e.g. per tablet, vial) ranged from 10.67 cent (levodopa + decarboxylase inhibitor) to 17,000 euro (ipilimumab). A total of 53% of the medicines surveyed had a unit ex-factory price (median) above 200 Euro. For two thirds of the medicines, price differences between the highest-priced country and lowest-priced country ranged between 25 and 100%; the remaining medicines, mainly low-priced medicines, had higher price differential, up to 251%. Medicines with unit prices of a few euros or less were medicines for the treatment of diseases in the nervous system (anti-depressants, medicines to treat Parkinson and for the management of neuropathic pain), of obstructive airway diseases and cardio-vascular medicines (lipid modifying agents). High priced medicines were particularly cancer medicines. CONCLUSION: Medicine prices of Greece, Hungary, Slovakia and UK were frequently at the lower end, German and Swedish, as well as Danish and Irish prices at the upper end. For high-priced medicines, actual paid prices are likely to be lower due to confidential discounts and similar funding arrangements between industry and public payers. Pricing authorities refer to the higher undiscounted prices when they use price data from other countries for their pricing decisions. PMID- 27658049 TI - Molecular Genetic Characterization of Individual Cancer Cells Isolated via Single Cell Printing. AB - Intratumoral genetic heterogeneity may impact disease outcome. Gold standard for dissecting clonal heterogeneity are single-cell analyses. Here, we present an efficient workflow based on an advanced Single-Cell Printer (SCP) device for the study of gene variants in single cancer cells. To allow for precise cell deposition into microwells the SCP was equipped with an automatic dispenser offset compensation, and the 384-microwell plates were electrostatically neutralized. The ejection efficiency was 99.7% for fluorescent beads (n = 2304) and 98.7% for human cells (U-2 OS or Kasumi-1 cancer cell line, acute myeloid leukemia [AML] patient; n = 150). Per fluorescence microscopy, 98.8% of beads were correctly delivered into the wells. A subset of single cells (n = 81) was subjected to whole genome amplification (WGA), which was successful in all cells. On empty droplets, a PCR on LINE1 retrotransposons yielded no product after WGA, verifying the absence of free-floating DNA in SCP-generated droplets. Representative gene variants identified in bulk specimens were sequenced in single-cell WGA DNA. In U-2 OS, 22 of 25 cells yielded results for both an SLC34A2 and TET2 mutation site, including cells harboring the SLC34A2 but not the TET2 mutation. In one cell, the TET2 mutation analysis was inconclusive due to allelic dropout, as assessed via polymorphisms located close to the mutation. Of Kasumi-1, 23 of 33 cells with data on both the KIT and TP53 mutation site harbored both mutations. In the AML patient, 21 of 23 cells were informative for a TP53 polymorphism; the identified alleles matched the loss of chromosome arm 17p. The advanced SCP allows efficient, precise and gentle isolation of individual cells for subsequent WGA and routine PCR/sequencing-based analyses of gene variants. This makes single-cell information readily accessible to a wide range of applications and can provide insights into clonal heterogeneity that were indeterminable solely by analyses of bulk specimens. PMID- 27658052 TI - Differing Alterations of Two Esca Associated Fungi, Phaeoacremonium aleophilum and Phaeomoniella chlamydospora on Transcriptomic Level, to Co-Cultured Vitis vinifera L. calli. AB - The filamentous fungi Phaeoacremonium aleophilum (P.al, Teleomorph: Togninia minima) and Phaeomoniella chlamydospora (P.ch) are believed to be causal agents of wood symptoms associated with the Esca associated young vine decline. The occurrence of these diseases is dramatically increasing in vineyards all over the world whereas efficient therapeutic strategies are lacking. Both fungi occupy the same ecological niche within the grapevine trunk. We found them predominantly within the xylem vessels and surrounding cell walls which raises the question whether the transcriptional response towards plant cell secreted metabolites is comparable. In order to address this question we co-inoculated grapevine callus culture cells with the respective fungi and analyzed their transcriptomes by RNA sequencing. This experimental setup appears suitable since we aimed to investigate the effects caused by the plant thereby excluding all effects caused by other microorganisms omnipresent in planta and nutrient depletion. Bioinformatics analysis of the sequencing data revealed that 837 homologous genes were found to have comparable expression pattern whereas none of which was found to be differentially expressed in both strains upon exposure to the plant cells. Despite the fact that both fungi induced the transcription of oxido- reductases, likely to cope with reactive oxygen species produced by plant cells, the transcriptomics response of both fungi compared to each other is rather different in other domains. Within the transcriptome of P.ch beside increased transcript levels for oxido- reductases, plant cell wall degrading enzymes and detoxifying enzymes were found. On the other hand in P.al the transcription of some oxido- reductases was increased whereas others appeared to be repressed. In this fungus the confrontation to plant cells results in higher transcript levels of heat shock and chaperon-like proteins as well as genes encoding proteins involved in primary metabolism. PMID- 27658051 TI - CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18. AB - Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) belong to the family of beta2 integrins and are expressed mainly by myeloid cell types in humans. Previously, we proved that CR3 rather than CR4 plays a key role in phagocytosis. Here we analysed how CD11b and CD11c participate in cell adhesion to fibrinogen, a common ligand of CR3 and CR4, employing human monocytes, monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs) highly expressing CD11b as well as CD11c. We determined the exact numbers of CD11b and CD11c on these cell types by a bead-based technique, and found that the ratio of CD11b/CD11c is 1.2 for MDDCs, 1.7 for MDMs and 7.1 for monocytes, suggesting that the function of CD11c is preponderant in MDDCs and less pronounced in monocytes. Applying state-of-the-art biophysical techniques, we proved that cellular adherence to fibrinogen is dominated by CD11c. Furthermore, we found that blocking CD11b significantly enhances the attachment of MDDCs and MDMs to fibrinogen, demonstrating a competition between CD11b and CD11c for this ligand. On the basis of the cell surface receptor numbers and the measured adhesion strength we set up a model, which explains the different behavior of the three cell types. PMID- 27658054 TI - Correction: Comparison of Transversus Abdominis Plane Infiltration with Liposomal Bupivacaine versus Continuous Epidural Analgesia versus Intravenous Opioid Analgesia. AB - [This corrects the article DOI: 10.1371/journal.pone.0153675.]. PMID- 27658053 TI - Genomic regions, cellular components and gene regulatory basis underlying pod length variations in cowpea (V. unguiculata L. Walp). AB - Cowpea (V. unguiculata L. Walp) is a climate resilient legume crop important for food security. Cultivated cowpea (V. unguiculata L) generally comprises the bushy, short-podded grain cowpea dominant in Africa and the climbing, long-podded vegetable cowpea popular in Asia. How selection has contributed to the diversification of the two types of cowpea remains largely unknown. In the current study, a novel genotyping assay for over 50 000 SNPs was employed to delineate genomic regions governing pod length. Major, minor and epistatic QTLs were identified through QTL mapping. Seventy-two SNPs associated with pod length were detected by genome-wide association studies (GWAS). Population stratification analysis revealed subdivision among a cowpea germplasm collection consisting of 299 accessions, which is consistent with pod length groups. Genomic scan for selective signals suggested that domestication of vegetable cowpea was accompanied by selection of multiple traits including pod length, while the further improvement process was featured by selection of pod length primarily. Pod growth kinetics assay demonstrated that more durable cell proliferation rather than cell elongation or enlargement was the main reason for longer pods. Transcriptomic analysis suggested the involvement of sugar, gibberellin and nutritional signalling in regulation of pod length. This study establishes the basis for map-based cloning of pod length genes in cowpea and for marker-assisted selection of this trait in breeding programmes. PMID- 27658055 TI - Evidence-Based Medicine and Key Reporting Guidelines: Should AJR Adopt These Approaches? PMID- 27658056 TI - The impact of autologous platelet concentrates on endodontic healing: a systematic review. AB - The current literature was reviewed to determine the impact of autologous platelet concentrates (APCs) on endodontic healing. All types of clinical study designs concerning any kind of endodontic treatment involving the application of APCs were included. Two independent reviewers searched three databases (PubMed, Embase, and Cochrane Library) for studies, complemented by hand search, until 16/1/2016. From the 423 identified records, 48 articles met the inclusion criteria. Selected randomized controlled clinical trials (RCTs) underwent Cochrane Collaboration's risk-of-bias assessment and data extraction. Only two RCTs showed low risk of bias. There was considerable heterogeneity between the RCTs with regard to the type of therapy, type of APCs, assessment method, and study quality, and therefore the data could not be analyzed quantitatively. The included case reports/series and non-randomized comparative studies underwent qualitative analysis with the revised Methodological Index for Non-Randomized Studies (MINORS) and data extraction. The two comparative non-randomized studies scored qualitatively high, though the MINORS-scores of the case series and reports were dispersed. APCs were involved in five endodontic treatment modalities, namely apexification, regenerative endodontic procedures, pulpotomy, apical surgery, and treatment of endo-perio/perio-endo lesions. APCs seem to accelerate postoperative bone healing, augment the patients' postoperative quality of life, aid further root development, and support maintenance/regaining of pulp vitality. No adverse events were reported. APCs in endodontic treatments seem to contribute to the healing of soft and hard tissues, though there is a lack of long-term high quality clinical trials and standardized treatment protocols. PMID- 27658057 TI - An Experimental Model of Vasovagal Syncope Induces Cerebral Hypoperfusion and Fainting-Like Behavior in Awake Rats. AB - Vasovagal syncope, a contributing factor to elderly falls, is the transient loss of consciousness caused by decreased cerebral perfusion. Vasovagal syncope is characterized by hypotension, bradycardia, and reduced cerebral blood flow, resulting in fatigue, altered coordination, and fainting. The purpose of this study is to develop an animal model which is similar to human vasovagal syncope and establish an awake animal model of vasovagal syncope. Male Sprague-Dawley rats were subjected to sinusoidal galvanic vestibular stimulation (sGVS). Blood pressure, heart rate, and cerebral blood flow were monitored before, during, and post-stimulation. sGVS resulted in hypotension, bradycardia, and decreased cerebral blood flow. One cohort of animals was subjected to sGVS while freely moving. sGVS in awake animals produced vasovagal syncope-like symptoms, including fatigue and uncoordinated movements; two animals experienced spontaneous falling. Another cohort of animals was preconditioned with isoflurane for several days before being subjected to sGVS. Isoflurane preconditioning before sGVS did not prevent sGVS-induced hypotension or bradycardia, yet isoflurane preconditioning attenuated sGVS-induced cerebral blood flow reduction. The sGVS rat model mimics elements of human vasovagal syncope pathophysiology (hypotension, bradycardia, and decreased cerebral perfusion), including behavioral symptoms such as fatigue and altered balance. This study indicates that the sGVS rat model is similar to human vasovagal syncope and that therapies directed at preventing cerebral hypoperfusion may decrease syncopal episodes and reduce injuries from syncopal falls. PMID- 27658058 TI - A perspective on single cell behavior during infection. AB - The interface between immune cells and intracellular bacterial pathogens produces complex, diverse interactions. During individual encounters, highly adaptable and dynamic host cells and bacteria vary in their responses, thereby contributing to well-documented heterogeneous outcomes of infection. The challenge now is to break down the multidimensionality of these interactions into informative readouts of population physiology and predictors of responses to infection. We recently reported one approach to this challenge that couples single cell RNA-seq analysis with fluorescent markers to characterize infection phenotype. 1 We detected bacterial subpopulations that elicit profoundly different host responses to infection in the specific host cells that they infect. Here we describe how heterogeneity might be maintained in populations of host and pathogens and discuss the advantages that heterogeneity confers to bacteria during infection and to host cells for eradicating a pathogen. We propose that single cell studies will allow the unraveling of host-pathogen biology and lead to an understanding of how the sum of individual encounters leads to the infection outcome of a whole organism. PMID- 27658059 TI - Accuracy of the Fluorescence-Activated Cell Sorting Assay for the Aquaporin-4 Antibody (AQP4-Ab): Comparison with the Commercial AQP4-Ab Assay Kit. AB - BACKGROUND: The aquaporin-4 antibody (AQP4-Ab) is a disease-specific autoantibody to neuromyelitis optica (NMO). We aimed to evaluate the accuracy of the FACS assay in detecting the AQP4-Ab compared with the commercial cell-based assay (C CBA) kit. METHODS: Human embryonic kidney-293 cells were transfected with human aquaporin-4 (M23) cDNA. The optimal cut off values of FACS assay was tested using 1123 serum samples from patients with clinically definite NMO, those at high risk for NMO, patients with multiple sclerosis, patients with other idiopathic inflammatory demyelinating diseases, and negative controls. The accuracy of FACS assay and C-CBA were compared in consecutive 225 samples that were collected between January 2014 and June 2014. RESULTS: With a cut-off value of MFIi of 3.5 and MFIr of 2.0, the receiver operating characteristic curve for the FACS assay showed an area under the curve of 0.876. Among 225 consecutive sera, the FACS assay and C-CBA had a sensitivity of 77.3% and 69.7%, respectively, in differentiating the sera of definite NMO patients from sera of controls without IDD or of MS. Both assay had a good specificity of 100% in it. The overall positivity of the C-CBA among FACS-positive sera was 81.5%; moreover, its positivity was low as 50% among FACS-positive sera with relatively low MFIis. CONCLUSIONS: Both the FACS assay and C-CBA are sensitive and highly specific assays in detecting AQP4-Ab. However, in some sera with relatively low antibody titer, FACS-assay can be a more sensitive assay option. In real practice, complementary use of FACS assay and C-CBA will benefit the diagnosis of NMO patients, because the former can be more sensitive among low titer sera and the latter are easier to use therefore can be widely used. PMID- 27658061 TI - Tele-rehabilitation using in-house wearable ankle rehabilitation robot. AB - This article explores wide-ranging potential of the wearable ankle robot for in house rehabilitation. The presented robot has been conceptualized following a brief analysis of the existing technologies, systems, and solutions for in-house physical ankle rehabilitation. Configuration design analysis and component selection for ankle robot have been discussed as part of the conceptual design. The complexities of human robot interaction are closely encountered while maneuvering a rehabilitation robot. We present a fuzzy logic-based controller to perform the required robot-assisted ankle rehabilitation treatment. Designs of visual haptic interfaces have also been discussed, which will make the treatment interesting, and the subject will be motivated to exert more and regain lost functions rapidly. The complex nature of web-based communication between user and remotely sitting physiotherapy staff has also been discussed. A high-level software architecture appended with robot ensures user-friendly operations. This software is made up of three important components: patient-related database, graphical user interface (GUI), and a library of exercises creating virtual reality-specifically developed for ankle rehabilitation. PMID- 27658060 TI - Associations of Various Health-Ratings with Geriatric Giants, Mortality and Life Satisfaction in Older People. AB - Self-rated health is routinely used in research and practise among general populations. Older people, however, seem to change their health perceptions. To accurately understand these changed perceptions we therefore need to study the correlates of older people's self-ratings. We examined self-rated, nurse-rated and physician-rated health's association with common disabilities in older people (the geriatric giants), mortality hazard and life satisfaction. For this, we used an age-representative population of 501 participant aged 85 from a middle-sized city in the Netherlands: the Leiden 85-plus Study. Participants with severe cognitive dysfunction were excluded. Participants themselves provided health ratings, as well as a visiting physician and a research nurse. Visual acuity, hearing loss, mobility, stability, urinal and faecal incontinence, cognitive function and mood (depressive symptoms) were included as geriatric giants. Participants provided a score for life satisfaction and were followed up for vital status. Concordance of self-rated health with physician-rated (k = .3 [.0]) and nurse-rated health (k = .2 [.0]) was low. All three ratings were associated with the geriatric giants except for hearing loss (all p < 0.001). Associations were equal in strength, except for depressive symptoms, which showed a stronger association with self-rated health (.8 [.1] versus .4 [.1]). Self-rated health predicted mortality less well than the other ratings. Self-rated health related stronger to life satisfaction than physician's and nurse's ratings. We conclude that professionals' health ratings are more reflective of physical health whereas self-rated health reflects more the older person's mental health, but all three health ratings are useful in research. PMID- 27658063 TI - Changes worth the fight. AB - April 1 saw many changes to the NHS: more Trusts, the community care reforms and a 1.5 per cent pay increase for nurses. But it was also the day North East Thames RHA announced the early retirement of Mary Spinks (nee Donn), a move that has justifiably fuelled rumours that regional nursing officers are rapidly becoming an extinct breed. PMID- 27658062 TI - Correction: The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases. AB - [This corrects the article DOI: 10.1371/journal.pone.0161672.]. PMID- 27658064 TI - ? AB - Shopping list: Nina Sakjarvi-Stenham (left) and Coco Leuong join Parkside Health Visitor Angie Glew (centre) outside a North London branch of Tesco to highlight the first ever Child Safety Week. Health Visitors and firemen demonstrated to shoppers how parents can make sure their children avoid bums and scalds, while health visitors and road safety officers visited branches of Mothercare last week to give travel safety advice. The Child Accident Prevention Trust says three children the every day as a result of accidents, which is the major cause of death in the under-14s. More than 10,000 children are permanently disabled by accidents every year. PMID- 27658065 TI - Fear for RNO posts as regions follow decree to 'slimdown'. AB - Fears are growing about the future of regional nursing officer posts following Health Secretary Virginia Bottomley's decree that regions slim down. PMID- 27658066 TI - Fundholders warned not to cut back. AB - Fundholding GPs will regret cutting back on community nurses if they use their new purchasing powers to insist on skill mix changes, the RCN warned last week. PMID- 27658067 TI - ? AB - District nurses from Liverpool delivered a petition to their MPs last week protesting about plans to restructure the service. MPs Eddie Loydon (holding the petition) and Peter Kilfoyle (second left front row) are shown with the nurses and Royal College of Nursing Regional Officer Maureen Woods (right). PMID- 27658068 TI - Less staff caring for more deliveries. AB - Six senior midwifery posts are being axed by Guy's and St Thomas' NHS Trust in an attempt to save cash. The Royal College of Midwives claimed a postnatal ward would now be left with only one qualified midwife to care for 18 mothers and babies. RCM Senior Industrial Relations Officer Barbara Shepherd said there would note be less qualified staff caring for more deliveries. 'The moves will make the situation intolerable, ' she added. A Trust spokesperson confirmed seven posts were to be cut - six in senior grades - as part of a rationalisation plan adopted by Guy's managers before the recent merger with St Thomas'. PMID- 27658069 TI - New trust hospital will have to 'take out' up to 70 posts. AB - A Surrey hospital which assumed Trust status last week is overspending by L10,000 a day and must make cuts that total L3.6 million, unions at the hospital have claimed. PMID- 27658070 TI - P2000 mental handicap branch may go. AB - Department of Health proposals to get rid of the mental handicap branch of Project 2000 and replace it with a new post-registration course have received a mixed response from the nursing profession. PMID- 27658071 TI - 'Nurses could be NHS accountants'. AB - Hospital finance managers should encourage nurses to take up a career in NHS accountancy, the head of health service finance says. PMID- 27658072 TI - A&E shuffle results in patient overload. AB - Changes to the delivery of care in Birmingham have left the city's Dudley Road Hospital 'bursting at the seams' with casualty patients, the RCN claimed last week. PMID- 27658073 TI - Drop in cot deaths not fully explained. AB - Nurses and midwives have welcomed the dramatic reduction in cot deaths announced last week but have said that factors other than the government's L2 million campaign could have contributed to the drop. PMID- 27658074 TI - Heavy job losses predicted. AB - More than 750 health workers lost their jobs last month, with nurses accounting for at least half of the casualties, according to Unison's Jobwatch Bulletin. PMID- 27658075 TI - NHS now spending more on complementary therapies. AB - The National Health Service is now spending L1 million a year on complementary therapies, a new survey shows. PMID- 27658076 TI - ? AB - Kids Stuff: Participants at the recent Northern Ireland RCN Paediatric Nursing Society Conference (from left, front) Alan (Rasper. Professor of Nursing. Southampton University: Elizabeth McElkerney. Clinical Services Manager, Ulster Hospital; Hilary Herron, Royal College of Nursing Paediatric Nursing Society Chair; Lynn Peyton, Assistant Director Social Services, Southern Health and Social Services Board; (Back) Rosemary Rogers, Editor, Paediatric Nursing, Frank Rice. Director of Nursing. Southern Area College of Nursing; Norah Casey, Editor, Nursing Standard: John Templeton, UGM, Craigavon Area Hospital; Anna Sidey, Paediatric Community Nurse Specialist; and Basil McNamee, Director of Acute Services, South Tyrone Hospital. PMID- 27658078 TI - No cash for courses on work violence. AB - Lack of funding is preventing the development of courses on coping with violence at work, a new report claims. PMID- 27658077 TI - Formal procedures block complaints. AB - Many dissatisfied NHS patients are deterred from complaining by a 'bewildering' array of formal procedures, according to Which?, the Consumers' Association magazine. PMID- 27658079 TI - World news. AB - United States An influential American human rights organisation has highlighted the problems of whistleblowing' British nurses who speak out over shortcomings in care. PMID- 27658081 TI - Understanding race and culture. AB - Race and cultural awareness should be built into basic nurse education, integrated with all aspects of the curriculum, Royal College of Nursing General Secretary Christine Hancock told the conference. PMID- 27658080 TI - Black professionals for equality of care. AB - More black and ethnic minority nurses are needed to ensure equality of care, an RCN conference on Race and Health heard recently. PMID- 27658082 TI - Parliament. AB - Coal miners have won an important victory with the government's acceptance of chronic bronchitis and emphysema as industrial injuries. PMID- 27658083 TI - Looking at the benefits of mixed wards. AB - Hospitals should only have mixed sex wards if patients benefit, even if single sex wards are more expensive, RCN General Secretary Christine Hancock told a conference in Dublin. PMID- 27658084 TI - Hepatitis B fears for healthcare workers. AB - Occupationally-acquired hepatitis B may kill a European healthcare worker almost every day of the year, new figures show. PMID- 27658086 TI - ? AB - Fool proof: Project worker Russell Goodwin pictured on April Fool's Day at the start of a 3,000 mile sponsored bike ride to raise money for a permanent site for Oxford's Luther Street Centre. This provides health care for homeless people, but is currently housed in a portacabin. PMID- 27658087 TI - Less choice of pill could mean more pregnancies. AB - More women will have unwanted pregnancies if the range of contraceptive pills available free on prescription is reduced, family planning nurses have warned. PMID- 27658088 TI - Growing dependency levels in the elderly. AB - Dependency levels among elderly people in residential care homes rose sharply during the Eighties, especially in the private sector, according to research. PMID- 27658089 TI - ? PMID- 27658090 TI - Ignorance of healing is preventing cures. AB - Most wounds in elderly patients' are maintained instead of cured because health professionals lack understanding of the basic processes that promote healing, a doctor has warned. PMID- 27658091 TI - Exposure to carcinogens increasing cancer risk? AB - The risk of developing cancer is increasing, probably because of greater exposure to carcinogens, according to Swedish research. PMID- 27658092 TI - Reducing neutropenia in cancer therapy. AB - The morbidity associated with chemotherapy induced neutropenia may be reduced by giving recombinant granulocyte colony stimulating factor. PMID- 27658093 TI - Vaccine against malaria shows promise. AB - Clinical trials of a synthesised vaccine against Plasmodium falciparum malaria show that it is safe, immunogenic and protective in semi-immune populations subject to natural challenge. PMID- 27658094 TI - Adolescents fear lack of confidentiality. AB - Adolescents may not use health services because of fears about confidentiality, American researchers report. PMID- 27658095 TI - Meningitis may mimic substance abuse. AB - Bacterial meningitis may present with acute behavioural disturbance that can closely mimic substance abuse. PMID- 27658096 TI - Care getting out of the car could help hips. AB - Disabling hip pain may be prevented or cured by taking care getting out of cars. PMID- 27658097 TI - A major milestone. AB - Several things combined to ensure that the implications of the UK Central Council's recent statement on PREP were almost lost in a barrage of supplementary questions. There was the issue of funding, for example. Would the government pay for the five statutory study days? PMID- 27658098 TI - Caring in a divided community. AB - The Order of St John's links with Jerusalem span 900 years. Returning to its roots in 1882, the St John Ophthalmic Hospital was opened in Jerusalem, the first of its kind in the Middle East. But the hospital has not been immune to the area's political troubles - during fighting which followed the end of the British mandate in 1948, it was so badly damaged that a new start was needed. PMID- 27658099 TI - Help yourself. AB - Considering the changes currently taking place in the NHS, it would be remarkable if staff were not under stress. PMID- 27658100 TI - You don't have to face bullying alone. AB - The more I read the article 'Bullying, I fought back' (Viewpoint, March 17), the angrier I became. PMID- 27658101 TI - And it happens in the private sector as well. AB - I felt great empathy for the author of'Bullying, I fought back' (Viewpoint, March 17), as I have been in a similar position - but when working in a nursing home, where I had neither a complaints procedure nor an RCN representative to turn to. PMID- 27658103 TI - Letters. AB - My health suffered, and eventually I left, in the same manner as others before me, with my confidence in tatters. A friend helped me back into the workplace, and now I am settled and happy working in the NHS. PMID- 27658102 TI - The plunge into disappointment. AB - I am a Project 2000 student, due to complete my education in mid-September. PMID- 27658104 TI - Putting students in their placement. AB - I am a Project 2000 student studying in Leicester, and wish to express my views about the appalling way in which some of my colleagues and I are treated by qualified staff members when we are on placement. PMID- 27658105 TI - That's no 'client', that's my relative. AB - Very recently, an in-law of mine, a frail man in his 70s, has been a patient in one of the local hospitals. The nursing care he received has made me angry and frustrated, and I have found myself unable to defend the actions of my 'profession' to the rest of my family. PMID- 27658106 TI - Information exchange. AB - * I am health visitor dealing with a family affected by neurofibromatosis. I would be interested to hear of any patient support group for this condition, or from health visitors with similar families who would like to build a parents' support group. PMID- 27658107 TI - Asthma at your fingertips Asthma at your fingertips AL Levy , S Hilton and G Barnes Class Publishing 240pp L11.95 1-872362-06-0. AB - Asthma at Your Fingertips, a new publication on asthma, is undoubtedly excellent value for money, particularly for those who suffer from asthma and for parents of children who are affected. PMID- 27658108 TI - A textbook of science for the health professions, 2nd edition A textbook of science for the health professions, 2nd edition B Hinwood Chapman & Hall 490pp L17.95 0-412-46730-5. AB - A Textbook of Science for the Health Professions is in 11 main sections containing 40 chapters. Each chapter has stated objectives for the reader with an excellent 18-page glossary and useful appendices for quick reference. PMID- 27658109 TI - Death, Dying and Bereavement D Dickenson Death, Dying and Bereavement and M Johnson , editors SAGE 320pp L12.95 0-8039-8797-8 [Formula: see text]. AB - Death, Dying and Bereavement is the course reader for the Open University course 'Death and Dying', which is offered as part of the Open University Diploma in Health and Social Welfare. PMID- 27658110 TI - Computing reviews Ziff-Davis B Howard press Distributed by computer Manuals 50 James road, Tyseley, Birmingham B11 2BA Tel: 021 706 6000 L27.95 1-56276-005-X. AB - If you use a computer, you are likely to be interested in laptops and notebooks. Both offer the power of a desktop computer with the convenience of the jumbo A4 pad of feint and margin. PMID- 27658111 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House. 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27658112 TI - The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28. AB - KRAB domain Zinc finger proteins are one of the most abundant families of transcriptional regulators in higher vertebrates. The prevailing view is that KRAB domain proteins function as potent transcriptional repressors by recruiting TRIM28 and promoting heterochromatin spreading. However, the extent to which all KRAB domain proteins are TRIM28-dependent transcriptional repressors is currently unclear. Our studies on mouse ZFP568 revealed that TRIM28 recruitment by KRAB domain proteins is not sufficient to warrant transcriptional repressive activity. By using luciferase reporter assays and yeast two-hybrid experiments, we tested the ability of ZFP568 and other mouse KRAB domain proteins to repress transcription and bind TRIM28. We found that some mouse KRAB domain proteins are poor transcriptional repressors despite their ability to recruit TRIM28, while others showed strong KRAB-dependent transcriptional repression, but no TRIM28 binding. Together, our results show that the transcriptional repressive activity of KRAB-ZNF proteins does not correlate with their ability to recruit TRIM28, and provide evidence that KRAB domains can regulate transcription in a TRIM28 independent fashion. Our findings challenge the current understanding of the molecular mechanisms used by KRAB domain proteins to control gene expression and highlight that a high percentage of KRAB domain proteins in the mouse genome differ from the consensus KRAB sequence at amino acid residues that are critical for TRIM28 binding and/or repressive activity. PMID- 27658113 TI - Cr(VI) Adsorption on Red Mud Modified by Lanthanum: Performance, Kinetics and Mechanisms. AB - Water pollution caused by the highly toxic metal hexavalent chromium (Cr(VI)) creates significant human health and ecological risks. In this study, a novel adsorbent was used to treat Cr(VI)-containing wastewater; the adsorbent was prepared using red mud (RM) generated from the alumina production industry and the rare earth element lanthanum. This study explored adsorption performance, kinetics, and mechanisms. Results showed that the adsorption kinetics of the RM modified by lanthanum (La-RM), followed the pseudo-second-order model, with a rapid adsorption rate. Cr(VI) adsorption was positively associated with the absorbent dose, pH, temperature, and initial Cr(VI) concentration; coexisting anions had little impact. The maximum Cr(VI) adsorption capacity was 17.35 mg/g. Cr(VI) adsorption on La-RM was a mono-layer adsorption pattern, following the Langmuir isotherm model. Thermodynamic parameters showed the adsorption was spontaneous and endothermic. The adsorption of Cr(VI) on La-RM occurred as a result of LaOCl formation on the RM surface, which in turn further reacted with Cr(VI) in the wastewater. This study highlighted a method for converting industrial waste into a valuable material for wastewater treatment. The novel absorbent could be used as a potential adsorbent for treating Cr(VI) contaminating wastewater, due to its cost-effectiveness and high adsorption capability. PMID- 27658114 TI - Therapeutic targets in fibrotic pathways. AB - The pathogenetic heterogeneity of pulmonary fibrosis yields both challenges and opportunities for therapy. Its complexity implicates a variety of cellular processes, signaling pathways, and genetics as drivers of disease. TGF-beta stimulation is one avenue, and is central to pro-fibrotic protein expression, leading to decreased pulmonary function. Here we report our recent findings, introducing the E3 ligase Fibrosis Inducing E3 Ligase 1 (FIEL1) as an important regulator of TGF-beta signaling through the selective degradation of PIAS4. FIEL1 exacerbates bleomycin-induced murine pulmonary fibrosis, while its silencing attenuates the fibrotic phenotype. Further, we developed a small molecule inhibitor of FIEL1 (BC-1485) that inhibits the degradation of PIAS4, and ameliorates fibrosis in murine models. New understanding of this pathway illustrates the many targeting opportunities among the complexity of pulmonary fibrosis in the continuing search for therapy. PMID- 27658115 TI - Optimal Cut-Offs of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to Identify Dysglycemia and Type 2 Diabetes Mellitus: A 15-Year Prospective Study in Chinese. AB - BACKGROUND: The optimal reference range of homeostasis model assessment of insulin resistance (HOMA-IR) in normal Chinese population has not been clearly defined. Here we address this issue using the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), a prospective population-based cohort study with long-term follow-up. MATERIAL & METHODS: In this study, normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were defined according to the 1998 World Health Organization criteria. Dysglycemia referred to IFG, IGT or T2DM. This study comprised two parts. Part one was a cross-sectional study involving 2,649 Hong Kong Chinese subjects, aged 25-74 years, at baseline CRISPS-1 (1995-1996). The optimal HOMA-IR cut-offs for dysglycemia and T2DM were determined by the receiver-operating characteristic (ROC) curve. Part two was a prospective study involving 872 subjects who had persistent NGT at CRISPS-4 (2010-2012) after 15 years of follow-up. RESULTS: At baseline, the optimal HOMA-IR cut-offs to identify dysglyceia and T2DM were 1.37 (AUC = 0.735; 95% confidence interval [CI] = 0.713-0.758; Sensitivity [Se] = 65.6%, Specificity [Sp] = 71.3%] and 1.97 (AUC = 0.807; 95% CI = 0.777-0.886; Se = 65.5%, Sp = 82.9%) respectively. These cut offs, derived from the cross-sectional study at baseline, corresponded closely to the 75th (1.44) and 90th (2.03) percentiles, respectively, of the HOMA-IR reference range derived from the prospective study of subjects with persistent NGT. CONCLUSIONS: HOMA-IR cut-offs, of 1.4 and 2.0, which discriminated dysglycemia and T2DM respectively from NGT in Southern Chinese, can be usefully employed as references in clinical research involving the assessment of insulin resistance. PMID- 27658117 TI - Contrasting preschoolers' verbal reasoning in an object-individuation task with young infants' preverbal feats. AB - Young infants infer a second object if shown an object apparently moving on a discontinuous path (Aguiar & Baillargeon, 2002; Spelke, Kestenbaum, Simons, & Wein, 1995). In three experiments, we examined whether children aged 3-6 years and adults would do the same in their verbal explanations of an apparent continuity violation. Presenting participants with video clips (Exp. 1 and 3) as well as live events (Exp. 2) of a toy locomotive apparently passing through a tunnel without appearing in a large opening in the middle, we found virtually no evidence for generations of two-object explanations of the critical test event in preschoolers. Some of the younger children even denied a continuity violation at first. When participants were familiarized to two identical objects instead of just one, they were more likely to realize that a second object was involved in the test events but, unlike adults (Exp. 3), most children nonetheless adhered to a one-object interpretation. Analyzing 3- and 5-year-old children's and adults' eye movements (Exp. 3), we found that children's difficulties to infer a second object from an apparent continuity violation were not caused by inappropriate looking strategies. We conclude that preschoolers' physical reasoning about the numerical identity of objects is not continuous with the preverbal reasoning of infants. Rather than being exclusively constrained by the output of basic object individuation processes, as in infants, it is also strongly influenced, in a top down manner, by prior beliefs. PMID- 27658116 TI - Immersed Boundary Models for Quantifying Flow-Induced Mechanical Stimuli on Stem Cells Seeded on 3D Scaffolds in Perfusion Bioreactors. AB - Perfusion bioreactors regulate flow conditions in order to provide cells with oxygen, nutrients and flow-associated mechanical stimuli. Locally, these flow conditions can vary depending on the scaffold geometry, cellular confluency and amount of extra cellular matrix deposition. In this study, a novel application of the immersed boundary method was introduced in order to represent a detailed deformable cell attached to a 3D scaffold inside a perfusion bioreactor and exposed to microscopic flow. The immersed boundary model permits the prediction of mechanical effects of the local flow conditions on the cell. Incorporating stiffness values measured with atomic force microscopy and micro-flow boundary conditions obtained from computational fluid dynamics simulations on the entire scaffold, we compared cell deformation, cortical tension, normal and shear pressure between different cell shapes and locations. We observed a large effect of the precise cell location on the local shear stress and we predicted flow induced cortical tensions in the order of 5 pN/MUm, at the lower end of the range reported in literature. The proposed method provides an interesting tool to study perfusion bioreactors processes down to the level of the individual cell's micro environment, which can further aid in the achievement of robust bioprocess control for regenerative medicine applications. PMID- 27658119 TI - Ethnoracial inequality and insurance coverage among Latino young adults. AB - Previous research has demonstrated that Latino young adults are uninsured at higher rates relative to other ethnoracial groups. Recent implementation of the 2010 Affordable Care Act (ACA) has increased access to health insurance for young adults, in part by maintaining health coverage through their parents until age 26. This paper examines patterns of Latino young adults' insurance coverage during early ACA implementation by addressing three questions: 1) To what extent do Latino young adults remain uninsured relative to their peers of other ethnoracial groups? 2) How do young adults' family socioeconomic background, immigrant characteristics, college enrollment, and employment status mediate their coverage? And, 3) do patterns of insurance coverage differ for employer provided coverage versus other sources of coverage (including parents' health insurance)? Using a 2011 representative sample of U.S.-born and 1.5-generation immigrant young adults in California, we find that Latinos are more likely than other ethnoracial groups to remain uninsured. While they are as likely as similar peers to obtain employer-provided health insurance, they are less likely to possess insurance through other sources (including their parents). This study contributes to our understanding of the limits of the ACA in reducing disparities in insurance coverage for Latinos by highlighting the importance of family socioeconomic background, immigrant characteristics, college enrollment, and employment in shaping coverage among this age group. PMID- 27658118 TI - Seeing conflict and engaging control: Experience with contrastive language benefits executive function in preschoolers. AB - Engaging executive function often requires overriding a prepotent response in favor of a conflicting but adaptive one. Language may play a key role in this ability by supporting integrated representations of conflicting rules. We tested whether experience with contrastive language that could support such representations benefits executive function in 3-year-old children. Children who received brief experience with language highlighting contrast between objects, attributes, and actions showed greater executive function on two of three 'conflict' executive function tasks than children who received experience with contrasting stimuli only and children who read storybooks with the experimenter, controlling for baseline executive function. Experience with contrasting stimuli did not benefit executive function relative to reading books with the experimenter, indicating experience with contrastive language, rather than experience with contrast generally, was key. Experience with contrastive language also boosted spontaneous attention to contrast, consistent with improvements in representing contrast. These findings indicate a role for language in executive function that is consistent with the Cognitive Complexity and Control theory's key claim that coordinating conflicting rules is critical to overcoming perseveration, and suggest new ideas for testing theories of executive function. PMID- 27658120 TI - No one sees the fathers: Israeli fathers' experience of feticide. AB - RATIONALE: Feticide, a relatively recent development in medical technology, is the practice of late-stage pregnancy termination. The practice of feticide and the individuals who are closely exposed to it - particularly the fathers- have been under-researched. OBJECTIVE: The current research aims to fill this lacuna, examining the experience of Israeli fathers whose fetuses underwent feticide. Israeli policy concerning late-stage termination of pregnancy is unique but corresponds with Israeli social norms that emphasize health in general and healthy children in particular. METHODS: Seventeen interviews with men who experienced the feticide of their fetuses were carried out. Interviews were analyzed using the principles of hermeneutic phenomenology as outlined by Ricoeur. RESULTS: The results indicate that men's experiences in this arena are socially constructed and limited by gender roles and expectations. The revealed themes address: (a) the lack of a socially constructed terminology; (b) the unclear definition of the feticide experience; (c) men's sense of obligation to protect themselves and others from the procedure and its ramifications, and (d) the policies and regulations used to exclude men from the feticide experience, and the strategies they use to exclude themselves. The results further revealed that while narrating their experiences, men re-examined their behaviors, raising retrospectively counterfactual thoughts about what should have been done differently. CONCLUSION: The findings highlight the interface between a personal experience and a social phenomenon. In conceptualizing the men's two opposing positions - one that embraces social expectations, as evident in the revealed themes; the other that questions fathers' conformity, as evident through their counterfactual thoughts -Dialogical Self Theory was useful. PMID- 27658121 TI - Towards a validation of surface-enhanced Raman scattering (SERS) for use in forensic science: repeatability and reproducibility experiments. AB - In order for a new analytical technique such as surface-enhanced Raman scattering (SERS) to be used in a routine manner, data and studies on the validation of the method are required. In that context, we performed a systematic study of the variability observed at different levels of the analytical procedure (i.e. respectively measurement, sampling, colloids aliquots, colloids batches, laboratories). Our goal is to provide data towards a qualitative validation of the technique for identification purposes. Three molecules of forensic interest were used as probes, respectively crystal violet, methamphetamine and 2,4,6 trinitrotoluene (TNT). We demonstrate that the method is repeatable with RSD and multivariate techniques (PCA). The % RSD at the different analytical stages vary between the molecules and the peaks considered. The repeatability is on the order of 2-6% for crystal violet, and 5-16% for TNT. Methamphetamine binds very weakly to the silver colloids giving much greater variability in the measurements (5 29%). We show that spectra measured in the same conditions (e.g. same laboratory and instrument), even a few days apart, are comparable and stable. The largest source of variation has been identified to be the measurement conditions and the associated random fluctuations in intensity (i.e. Brownian motion of the particles, solvent evaporation and concentration). The influence of the substrate is confirmed to be negligible. However, the reproducibility between different laboratories and different instruments introduced the largest source of variability (~ 10-70%). Despite these factors, we demonstrate that qualitative identification of the species under analysis by measurement and comparison of peaks position is always successful even though quantitative analysis is, at present, difficult. Regardless of the amount of variability determined, the molecules could always be successfully identified, even on different instruments from different laboratories by utilizing the criterion proposed in the literature (i.e. 3:1 signal-to-noise ratio). PMID- 27658122 TI - Expression of Dopamine Receptor 1A and Cannabinoid Receptor 1 Genes in the Cochlea and Brain after Salicylate-Induced Tinnitus. AB - The purpose of this study was to investigate the mRNA expression of the dopamine receptor 1A (DR1A) and cannabinoid receptor 1 (CR1) genes in mice with tinnitus. Sixteen 3-month-old male SAMP8 mice were randomly and equally divided into two groups (8 mice in each group): a control (saline-treated) group and a tinnitus (salicylate-treated) group. The mRNA expression of the DR1A and CR1 genes in the cochleae and brains of the mice was evaluated after tinnitus had been induced by intraperitoneal injection of sodium salicylate (300 mg/kg body weight). The results showed that 4-day salicylate treatment (unlike 4-day saline treatment) caused a significant increase in the tinnitus score and in mRNA expression of the DR1A gene in the cochlea, the brainstem and inferior colliculus, the hippocampus and parahippocampus, and the temporal lobe, but not the frontal lobe. Conversely, 4-day salicylate treatment caused significantly lower mRNA expression of the CR1 gene in the cochlea and all the brain areas tested. In summary, salicylate induced tinnitus may be associated with increased mRNA expression of the DR1A gene - but with decreased mRNA expression of the CR1 gene - in the cochlea and in many tinnitus-related brain areas. PMID- 27658123 TI - Occlusal Caries: Biological Approach for Its Diagnosis and Management. AB - The management of occlusal caries still remains a major challenge for researchers as well as for general practitioners. The present paper reviews and discusses the most up-to-date knowledge and evidence of the biological principles guiding diagnosis, risk assessment, and management of the caries process on occlusal surfaces. In addition, it considers the whole spectrum of the caries process on occlusal surfaces, ranging from the molecular ecology of occlusal biofilms to the management of deep occlusal caries lesions. Studies using molecular methods with focus on biofilms in relation to occlusal caries should explore the relationship between the function and the structural composition of these biofilms to understand the role of occlusal biofilms in caries development. State-of-the-art measures to evaluate risk for occlusal caries lesion activity, caries incidence, and progression should include the assessment of the occlusal biofilm and the stage of tooth eruption. Careful clinical examination of non-cavitated lesions, including assessment of the lesion activity status, remains the major tool to determine the immediate treatment need and to follow on the non-operative treatment outcome. Even medium occlusal caries lesions in the permanent dentition may be treated by non-invasive fissure sealing. By extending the criteria for non invasive treatments, traditional restoration of occlusal surfaces can be postponed or even avoided, and the dental health in children and adolescents can be improved. Selective removal (incomplete) to soft dentin in deep carious lesions has greater success rates than stepwise excavation. Selective (complete) removal to firm dentin has a lower success rate due to increased pulp exposure. PMID- 27658124 TI - Prostaglandin synthesis by the porcine corpus luteum: effect of tumor necrosis factor-alpha. AB - The porcine corpus luteum (CL) displays delayed sensitivity to PGF-2alpha (luteolytic sensitivity, [LS]) until days 12 to 13 of cycle. The control of LS is unknown, but it is temporally associated with macrophage (which secrete tumor necrosis factor-alpha; TNF-alpha) infiltration into the CL. Other studies showed that TNF-alpha induces LS in vitro and that prostaglandins (PGs) may be involved in this mechanism. In experiment 1, PGF-2alpha and PGE secretion by luteal cells (LCs) was measured on days 4 to 14 of the estrous cycle, and the expression of PTGFS/AKR1B1 and PTGES/mPGES-1, determined by Western blot, before (day 7) vs after (day 13) the onset of LS. Results showed that the PGF-2alpha:PGE ratio increased significantly (P < 0.05) from day 4 to 13-14, and PTGFS/AKR1B1 and PTGES/mPGES-1 were significantly increased (P < 0.05) on day 13 (vs day 7). In experiment 2, LCs were collected from porcine CL at early (~days 4-6) or mid (~days 7-12) stages of the estrous cycle and cultured with 0, 0.1, 1, or 10 ng/mL TNF-alpha. Results showed that TNF-alpha significantly increased (P < 0.05) messenger RNA (mRNA) expression of cyclooxygenase (COX)-2 and mPGES-1 but not AKR1B1. TNF-alpha had no significant effects on AKR1B1 or mPGES protein abundance. TNF-alpha significantly increased (P < 0.05) PGE-2 but had no effect on PGF-2alpha secretion or on the PGF-2alpha:PGE2 ratio. In conclusion, although TNF-alpha increased COX2 and mPGES-1 mRNA, and PGE-2 secretion in vitro, it did not increase the PGF-2alpha:PGE2 ratio. Studies are currently directed toward exploring other pathways (eg, FP receptor signaling) by which TNF-alpha induces LS in the porcine CL. PMID- 27658126 TI - Brief report: Factor structure of parenting behaviour in early adolescence. AB - Researchers have traditionally relied on a tripartite model of parenting behaviour, consisting of the dimensions parental support, psychological control, and behavioural control. However, some scholars have argued to distinguish two dimensions of behavioural control, namely reactive control and proactive control. In line with earlier work, the current study found empirical evidence for these distinct behavioural control dimensions. In addition, the study showed that the four parenting dimensions of parental support, psychological control, reactive control, and proactive control were differentially related to peer-related loneliness as well as parent-related loneliness. Thereby, the current study does not only provide empirical evidence for the distinction between various parenting dimensions, but also shows the utility of this differentiation. PMID- 27658127 TI - Hybrid textile heart valve prosthesis: preliminary in vitro evaluation. AB - Transcatheter aortic valve implantation (TAVI) is nowadays a popular alternative technique to surgical valve replacement for critical patients. Biological valve tissue has been used in these devices for over a decade now with over 100,000 implantations. However, material degradations due to crimping for catheter insertion purpose have been reported, and with only 6-year follow-up, no information is available about the long-term durability of biological tissue. Moreover, expensive biological tissue harvesting and chemical treatment procedures tend to promote the development of synthetic valve leaflet materials. Textile polyester (PET) material is characterized by outstanding folding and strength properties combined with proven biocompatibility and could therefore be considered as a candidate to replace biological valve leaflets in TAVI devices. Nevertheless, the material should be preferentially partly elastic in order to limit water hammer effects at valve closing time and prevent exaggerated stress from occurring into the stent and the valve. The purpose of the present work is to study in vitro the mechanical as well as the hydrodynamic behavior of a hybrid elastic textile valve device combining non-deformable PET yarn and elastic polyurethane (PU) yarn. The hybrid valve properties are compared with those of a non-elastic textile valve. Testing results show improved hydrodynamic properties with the elastic construction. However, under fatigue conditions, the interaction between PU and PET yarns tends to limit the valve durability. PMID- 27658125 TI - Cell migration, viability and tissue reaction of calcium hypochlorite based solutions irrigants: An in vitro and in vivo study. AB - OBJECTIVE: This study aimed to analyze in vitro cytotoxicity to cultured 3T3 fibroblasts and in vivo inflammatory reaction in rats by calcium hypochlorite (Ca(OCl)2) solutions compared with sodium hypochlorite (NaOCl) solutions. DESIGN: Cultured 3T3 fibroblasts were exposed to different concentrations of (Ca(OCl)2) and NaOCl solutions, and a scratch assay was performed. The viability rate was analyzed with trypan blue assay. Both solutions of 1% and 2.5% concentrations were injected into the subcutaneous tissue of 18 male Wistar rats aged 18 weeks. The inflammatory tissue reaction was evaluated at 2h, 24h, and 14days after the injections. The samples were qualitatively analyzed using a light microscope. Statistical analysis was performed with ANOVA and Tukey post hoc tests for in vitro assays and Kruskal-Wallis and Dunn post hoc tests for in vivo assays (alpha=0.05). RESULTS: In the scratch assay, Ca(OCl)2 showed no significant difference compared with the control group (culture medium) at 24h (p<0.05). Solutions of 0.0075% and 0.005% NaOCl and Ca(OCl)2 concentrations presented similar results compared with those in the positive control group (hydrogen peroxide) (p>0.05) in the trypan blue assay. In the in vivo assay, 1% Ca(OCl)2 group showed a significant decrease in neutrophils at 2h and 24h (p=0.041) and 2h and 14days (p=0.017). There was no statistically significant difference for lymphocyte/plasmocyte and macrophage counts among the different concentration groups. CONCLUSIONS: Ca(OCl)2 showed favorable results of viability and induced a low-level inflammatory response. Ca(OCl)2 presented acceptable cytotoxicity and biocompatibility as an irrigant solution. PMID- 27658128 TI - An unusually long electric wire in a urethra and bladder. AB - Foreign bodies in the urethra and bladder are mostly due to self-insertion, iatrogenic insertion, migration from surrounding organs or through penetrating injuries. Self-insertion of a foreign body through the urethra is mostly related to sexual gratification, psychiatric conditions or to get relief from the intractable voiding symptoms. We present a case of a 17-year-old male who self introduced an extremely long 120 cm electrical wire into his bladder for sexual gratification. The wire was removed by supra-pubic cystotomy to avoid urethral injuries. PMID- 27658129 TI - Prevalence of physical inactivity and its association on oral conditions in adolescents. AB - BACKGROUND: The Brazilian population presents an ever-increasing number of sedentary people with poor oral health issues, including children and adolescents. Both physical inactivity and poor oral health have shown associations with various systemic diseases. OBJECTIVE: The aim of this study was to verify the association between physical inactivity and oral health conditions. SUBJECTS: Three hundred and fifty-three adolescents (mean age 13 and 17 years). METHODS: An epidemiological cross-sectional study. Assessment of the presence of caries was made by using the decayed, missing, filled (DMF) index. Gingival bleeding and quality of oral hygiene were also examined to evaluate the oral conditions. The International Physical Activity Questionnaire (PAQ-C) was used to assess physical activity. The confidence parameter was set at p=0.05. RESULTS: The results of this study showed that 74.3% were sedentary adolescents, the great majority of whom were girls (86.4%, p=0.001). There was a positive association between sedentary lifestyle and tooth decay (p=0.001), dental plaque (p=0.009), and time spent watching television (p=0.001). CONCLUSION: This study concluded that there was a positive association between physical inactivity and poor oral health. PMID- 27658130 TI - One month of omega-3 fatty acid supplementation improves lipid profiles, glucose levels and blood pressure in overweight schoolchildren with metabolic syndrome. AB - BACKGROUND: This study sought to investigate the effects of omega (omega)-3 polyunsaturated fatty acid (PUFA) supplementation on the lipid profiles and glucose (GLU) levels of overweight (OW) schoolchildren with metabolic syndrome (MS). METHODS: Thirty-nine OW schoolchildren with MS, including 19 girls and 20 boys, received 1-month of dietary supplementation with gel capsules containing omega-3 fatty acids. Fasting lipid profiles and GLU levels were measured before and after supplementation. RESULTS: Both sexes of OW schoolchildren with MS who received daily supplementation with 2.4 g of omega-3 fatty acids for 1 month displayed improved lipid profiles, reduced fasting GLU levels and reduced blood pressure (BP). CONCLUSIONS: These findings support the addition of omega-3 fatty acid supplementation to programs aiming to improve the metabolic status of OW children with MS, although additional research on the longer-term safety and efficacy of this treatment in this population is required. PMID- 27658131 TI - Fertility and sexual function: a gap in training in pediatric endocrinology. AB - BACKGROUND: Infertility and sexual dysfunction result from many different pediatric conditions and treatments and can profoundly impact quality of life. The American Academy of Pediatrics (AAP) has recommended consulting "fertility specialists" for counseling, but it remains unclear who these specialists are. Our objective was to assess whether pediatric subspecialists who manage hypogonadism and/or genitourinary conditions feel adequately trained to provide fertility and sexual function counseling. METHODS: An online survey was distributed to members of Pediatric Endocrine Society (PES), Society for Pediatric Urology (SPU), and North American Society for Pediatric and Adolescent Gynecology (NASPAG). Providers' comfort in counseling various age groups about fertility and sexual function was assessed via a five-point Likert scale. Providers reported whether they felt adequately trained in these areas. RESULTS: Two hundred and eighty-four surveys were completed by endocrinologists, 124 surveys by urologists, and 41 surveys by gynecologists. Respondents (44% male, 86% Caucasian) represented 39 states and Canada. Seventy-nine percent were at academic centers. Thirty-four percent of providers had been practicing for >20 years. Comfort level was variable and lowest in young males. Ninety-one percent of pediatric endocrinologists reported routinely seeing patients at risk for infertility, but only 36% felt adequately trained in fertility, and 25% felt adequately trained in sexual function. CONCLUSIONS: Infertility and sexual dysfunction are often overlooked in pediatric care. Our results suggest that pediatric endocrinologists, who frequently manage male and female hypogonadism, should also receive formal training in these areas. Optimizing counseling would help prevent missed opportunities for fertility preservation and alleviate distress among patients and families. PMID- 27658132 TI - Relationship between 25(OH)D levels and circulating lipids in African American adolescents. AB - BACKGROUND: Vitamin D deficiency is commonly seen among African American adolescents. Lipid levels during childhood are excellent predictors of adult dyslipidemia and atherosclerosis. There is a paucity of data on the relationship between 25 hydroxy vitamin D [25(OH)D] levels and lipids among African American adolescents. The objective of this study was to determine if there is an association between 25(OH)D levels and circulating lipids in African American adolescents residing in midwestern United States. METHODS: African American adolescents residing in Rochester, MN (latitude 44 degrees N), USA, underwent measurements of 25(OH)D and lipids following overnight fast. Pearson's correlation test, linear regression model and scatter plots were used to explore the association between 25(OH)D levels and lipids. RESULTS: 25(OH)D levels <30 ng/mL were seen in 21/24 (87%) of the subjects. 25(OH)D levels were inversely correlated with total cholesterol (r=-0.42; p=0.040) and with non-high-density lipoprotein (non-HDL) cholesterol (r=-0.42; p=0.040 ). These associations remained statistically significant after adjustment for age, gender and adiposity. In the multivariate linear regression model, and after adjusting for BMI Z-score, each 1 ng/mL increase in 25(OH)D was associated with a decrease in total cholesterol of 1.38 mg/dL (95% CI: -2.63, -0.14, p=0.030) and with a decrease in non-HDL cholesterol of 1.14 mg/dL (95% CI: -2.09, -0.18, p=0.020). CONCLUSIONS: 25(OH)D levels were inversely correlated with total cholesterol and non-HDL cholesterol levels in African American adolescents residing in midwestern United States. Further studies with larger sample sizes are needed to determine if low vitamin D status in African American adolescents is a potential modifiable risk factor for cardiovascular disease. PMID- 27658134 TI - Systematic review and meta-analysis of the association between mumps during childhood and risk of type 1 diabetes mellitus. AB - We conducted a systematic review and meta-analysis of the association between mumps and risk of type 1 diabetes mellitus (T1DM). Literature searches were conducted using Medline, EMBASE and Web of Science including studies published before February 2014. Crude and, where available, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from the published reports of each included study. Combined OR estimates and tests of heterogeneity were obtained using meta-analysis techniques. The analysis was repeated in subgroups of studies on the basis of quality defined by the score on the Newcastle-Ottawa scale (NOS). In total, 18 articles met the eligibility criteria, and overall there was some evidence of a weak association between clinically diagnosed mumps and T1DM (OR=1.23, 95% CI 1.00-1.51; p=0.05) but marked heterogeneity between studies (I2=49%; p for heterogeneity=0.01). Restricting analyses to 13 high quality studies, there was little evidence of association between clinically diagnosed mumps and T1DM (OR=1.11, 95% CI 0.91-1.35; p=0.29) and there was much less heterogeneity (I2=26%; p for heterogeneity=0.18). Overall there was little evidence of any strong association between mumps infection and T1DM. PMID- 27658133 TI - Glycemic variability predicts inflammation in adolescents with type 1 diabetes. AB - BACKGROUND: Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities. METHODS: This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A1c (HbA1c), and HbA1c*duration area under the curve (A1cDur). RESULTS: Seventeen adolescents (8 F/9M; age, 13.1+/-1.6 years (mean+/-SD); duration, 4.8+/-3.8 years, BMI, 20.3+/ 3.1 kg/m2; A1c, 8.3+/-1.2%) were studied. Log CRP but was not related to age, duration, body mass index (BMI), HbA1c, or A1cDUR. TAOC increased as logA1cDUR increased (n=13, r=0.61, p=0.028). CRP and sICAM were not related to CGM average glucose but log CRP increased as 3 day glucose standard deviation increased (r=0.66, p=0.006). TAOC increased as glucose standard deviation increased (r=0.63, p=0.028). CONCLUSIONS: Increased glucose variability is associated with increased inflammation in adolescents withT1D. Increased TAOC with increasing variability may be an effort to compensate for the ongoing oxidative stress. PMID- 27658135 TI - Ethnicity and incidence of congenital hypothyroidism in the capital of Macedonia. AB - BACKGROUND: Congenital hypothyroidism (CH) is a common and preventable cause of intellectual disability for which early diagnosis is difficult without newborn screening. Genetic and environmental factors, race, ethnicity, sex, and pregnancy outcomes were noted as risk factors. In the study we aimed to determine the incidence of CH among different ethnic groups in the capital of Macedoina - a multiethnic city. METHODS: A 14-year retrospective cohort analysis was performed on 121,507 newborns in the capital of Macedonia, Skopje, screened for whole-blood thyroid-stimulating hormone (TSH), in dry blood spots collected 48-72 h after birth, during the period 2002-2015. A TSH value of 15 mIU/L was used as cutoff point until 2010 and 10 mIU/L thereafter. RESULTS: Primary CH was detected in 46 newborns (female to male ratio 1.3) with overall incidence of 3.8/10,000 (1/2641). The incidence of primary CH was significantly increased after lowering the TSH cutoff value (p=0.038), primarily due to detected neonates with transient CH for this period. Ethnic differences in the incidence of primary CH were detected. CH incidence among Roma neonates (6.7/10,000) was significantly higher (p<0.05) than the incidence detected in Macedonians (3.9/10,000) or Albanians (3.7/10,000). CONCLUSIONS: Increased incidence of CH in Roma newborns was detected as compared to other ethnicities in the capital of Macedonia. Further analysis of factors in direct interrelationship with the increased CH incidence in Roma newborns, as well as elucidation of impact of the CH incidence in this ethnicity on the overall incidence in Skopje, is warranted. PMID- 27658136 TI - Prevalence and risk factors for diabetic retinopathy in a hospital-based population of Australian children and adolescents with type 1 diabetes. AB - BACKGROUND: The aim of this study was to investigate the prevalence of, and traditional and emerging risk factors associated with, retinopathy in a hospital based population of Australian children and adolescents with type 1 diabetes. METHODS: This was a cross-sectional study of 483 children and adolescents with type 1 diabetes. Medical files were audited to collect all relevant clinical data. Diabetic retinopathy was assessed from colour retinal images by an ophthalmologist. RESULTS: Diabetic retinopathy was observed in 11 (2.3%) participants. Logistic regression revealed that the principal components analysis derived risk profile of: higher serum creatinine, older age, higher systolic blood pressures, higher body mass index, abnormal estimated glomerular filtration rate (eGFR) (<59 mL/min), lower high density lipoproteins (HDL) cholesterol, higher serum sodium, longer duration of diabetes and narrower retinal arteriolar calibre was associated with diabetic retinopathy (ExpB=2.60, 95% CI 1.36/4.96, p=0.004). CONCLUSIONS: These results support the concept that the pathogenesis of diabetic retinopathy is likely due to the combined influence of various risk factors, many already identified. PMID- 27658137 TI - Seroprotection status of hepatitis B and measles vaccines in children with type 1 diabetes mellitus. AB - BACKGROUND: Type 1 diabetes mellitus (T1DM) is speculated to have an impaired immunological response to vaccines. This paper aimed to investigate the presence of specific antibodies against hepatitis B virus (HBV) and measles in diabetic children who had been immunized according to the standard national calendar of immunization. METHODS: Two hundred and one diabetic children and 140 healthy controls were prospectively evaluated. Antibodies against hepatitis B (anti-HBs) and measles were detected in all individuals who completed the vaccination schedule. We noted onset of T1DM, duration of the disease, diabetes-related autoantibodies and mean HbA1c levels. RESULTS: Some 72.6% of diabetics and 82.1% of controls had anti-HBs (+) (p=0.04). We found a reduced efficacy of measles vaccination in anti-HBs (-) diabetic children (p=0.009), even though there was no significant difference between the study and control groups. Onset of the disease was earlier in anti-HBs (-) diabetics than in controls (p=0.038). No difference with respect to other parameters was found. CONCLUSIONS: Our data showed a reduced seroprotection rate for HBV vaccination in diabetic children and for measles with anti-HBs (-) diabetics. Larger studies should be encouraged to confirm the vaccine efficacy in diabetic children and to elucidate possible pathogenic mechanisms. PMID- 27658138 TI - Antioxidant and acetylcholinesterase inhibitory activities of leaf extract and fractions of Albizia adianthifolia (Schumach) W.F. Wright. AB - BACKGROUND: This study was conducted to determine the antioxidant and acetylcholinesterase inhibitory activities of the leaf extract and different fractions of Albizia adianthifolia (Schumach.) W. Wright, and also to identify and quantify some phenolic compounds in the extract. METHODS: The antioxidant and acetylcholinesterase inhibitory activities of the methanol extract (CME), ethyl acetate (EAF), chloroform (CHF), and n-hexane (NHF) fractions of A. adianthifolia leaves were subjected to in vitro chemical analyses. RESULTS: Phytochemical screening revealed important classes of secondary metabolites. All extracts showed good antioxidant and acetylcholinesterase inhibitory activities. The EAF and CHF gave the highest total phenolic contents of 18.02+/-0.14 and 18.43+/-0.95 mg gallic acid equivalent per gram of extract, respectively. The polar extracts gave the highest activity in both assays with lower IC50 values. In the 2,2 diphenyl-1-picrylhydrazyl free-radical scavenging activity assay, the IC50 values of CME, EAF, CHF, and NHF were 77.74+/-0.84, 55.76+/-2.30, 58.47+/-0.72, and 232.24+/-2.70 ug/mL, respectively, while in the acetylcholinesterase inhibitory assay, the IC50 values of CME, EAF, CHF, and NHF were 11.80+/-0.88, 10.04+/-1.67, 17.44+/-1.74, and 124.38+/-1.51 ug/mL, respectively. CONCLUSIONS: The results of this study suggest that the leaf of A. adianthifolia could serve as a potential candidate for future search of antioxidant and acetylcholinesterase inhibitors for the management of neurodegenerative disorders such as Alzheimer's disease. PMID- 27658139 TI - alpha-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice. AB - BACKGROUND: Smoking during pregnancy is associated with numerous fetal and developmental complications and reproductive dysfunctions in the offspring. Nicotine is one of the key chemicals of tobacco responsible for addiction. The present study was aimed to investigate the protective role of alpha-lipoic acid (ALA) during the transplacental nicotine-induced germ cell and DNA damage in the offspring of Swiss mice. METHODS: Pregnant mice were treated with nicotine (20 mg/kg/day) in drinking water from 10 to 20 days of gestation period, and ALA (120 mg/kg/day) was administered orally for the same period. Endpoint of evaluation includes general observations at delivery and throughout the study, litter weight and size, sperm count and sperm head morphology, while structural damages and protein expression were assessed by histology and immunohistochemistry, respectively. RESULTS: Maternal nicotine exposure led to decreased growth rate, litter and testicular weight, testosterone level, 3beta-HSD expression and sperm count as well as increased sperm head abnormalities, micronucleus frequency and 8 oxo-dG positive cells, and the effects have been restored by ALA supplementation. CONCLUSIONS: The present study clearly demonstrated that ALA ameliorates nicotine associated oxidative stress, DNA damage and testicular toxicity in the offspring by improving steroidogenesis, spermatogenesis and sperm count. PMID- 27658140 TI - Ashanti pepper (Piper guineense Schumach et Thonn) attenuates carbohydrate hydrolyzing, blood pressure regulating and cholinergic enzymes in experimental type 2 diabetes rat model. AB - BACKGROUND: Ashanti pepper (Piper guineense Schumach et Thonn) seed is well known in folkloric medicine in the management of type 2 diabetes (T2DM) with little or no scientific documentation for its action. This study investigated the effect of Ashanti pepper seed on some enzymes relevant to carbohydrate hydrolysis, blood regulation and the cholinergic system, as well as the blood glucose level, lipid profile, antioxidant parameters, and hepatic and renal function markers in T2DM rats. METHODS: T2DM was induced by feeding rats with high-fat diet (HFD) for 14 days followed by a single intraperitoneal dose of 35 mg/kg body weight of streptozotocin (STZ). Three days after STZ induction, diabetic rats were placed on a dietary regimen containing 2%-4% Ashanti pepper. RESULTS: Reduced blood glucose level with decreased alpha-amylase, alpha-glucosidase and angiotensin I converting enzyme (ACE) activities were observed in Ashanti pepper seed and acarbose-treated rat groups when compared to that of the diabetic control rat group. Furthermore, the results revealed that inclusion of 2%-4% Ashanti pepper seed in diabetic rat fed group diets may ameliorate the lipid profile, antioxidant status, and hepatic and renal function in T2DM rats as much as in the acarbose-treated groups. In addition, a chromatographic profile of the seed revealed the presence of quercitrin (116.51 mg/g), capsaicin (113.94 mg/g), dihydrocapsaicin (88.29 mg/g) and isoquercitrin (74.89 mg/g). CONCLUSIONS: The results from this study clearly suggest that Ashanti pepper could serve as a promising source of phenolic compounds with great alternative therapeutic potentials in the management of T2DM. PMID- 27658141 TI - Comparative studies on the effects of clinically used anticonvulsants on the oxidative stress biomarkers in pentylenetetrazole-induced kindling model of epileptogenesis in mice. AB - BACKGROUND: Oxidative stress plays a key role in the pathogenesis of epilepsy and contributes in underlying epileptogenesis process. Anticonvulsant drugs targeting the oxidative stress domain of epileptogenesis may provide better control of seizure. The present study was carried out to investigate the effect of clinically used anti-epileptic drugs (AEDs) on the course of pentylenetetrazole (PTZ)-induced kindling and oxidative stress markers in mice. METHODS: Six mechanistically heterogeneous anticonvulsants: phenobarbital, phenytoin, levetiracetam, pregabalin, topiramate, and felbamate were selected and their redox profiles were determined. Diazepam was used as a drug control for comparison. Kindling was induced by repeated injections of a sub-convulsive dose of PTZ (50 mg/kg, s.c.) on alternate days until seizure score 5 was evoked in the control kindled group. Anticonvulsants were administered daily. Following PTZ kindling, oxidative stress biomarkers were assessed in homogenized whole brain samples and estimated for the levels of nitric oxide, peroxide, malondialdehyde, protein carbonyl, reduced glutathione, and activities of nitric oxide synthase and superoxide dismutase. RESULTS: Biochemical analysis revealed a significant increase in the levels of reactive oxygen species with a parallel decrease in endogenous anti-oxidants in PTZ-kindled control animals. Daily treatment with levetiracetam and felbamate significantly decreased the PTZ-induced seizure score as well as the levels of nitric oxide (p<0.001), nitric oxide synthase activity (p<0.05), peroxide levels (p<0.05), and malondialdehyde (p<0.05). Levetiracetam and felbamate significantly decreased lipid and protein peroxidation whereas topiramate was found to reduce lipid peroxidation only. CONCLUSIONS: An AED that produces anticonvulsant effect by the diversified mechanism of action such as levetiracetam, felbamate, and topiramate exhibited superior anti-oxidative stress activity in addition to their anticonvulsant activity. PMID- 27658142 TI - Blepharospasm: an uncommon adverse effect caused by long-term administration of olanzapine. AB - BACKGROUND: Blepharospasm is one of the components of drug-induced Meige's syndrome which is reported to be caused by typical antipsychotics. Reports of blepharospasm or Meige's syndrome caused by atypical antipsychotics are rare. CASE: A 30-year-old female patient presented to psychiatry out patient department (OPD) with chief complaints of inability to keep her eyes open for long and excessive blinking for 2 months, irritation of eyes, watery discharge from eyes and photophobia for last 1 month. The patient had been taking olanzapine 10 mg, sertraline 100 mg and divalproex sodium 500 mg per orally on once a day basis for the management of major depressive disorder with psychotic features for last 6 months. Routine blood analysis, thyroid function, EEG, MRI, lipid profile did not reveal any abnormality. Ocular examination was also within normal limits. Olanzapine was suspected as a culprit for the above symptoms of patient, so it was replaced with quetiapine 25 mg/day. Patient showed partial recovery of symptoms within 1 week and complete recovery within 2 months of stopping olanzapine. Causality of olanzapine-induced blepharospasm as per WHO-UMC scale was probable. CONCLUSIONS: Olanzapine (atypical antipsychotics) should also be kept in the list of suspected drugs causing blepharospasm in psychotic patients on treatment although further similar evidences from observational studies and/or reports are needed to establish the causal relationship. PMID- 27658143 TI - The effect of aqueous leaf extract of Telfairia occidentalis (Cucurbitaceae) on gentamycin-induced renal damage. AB - BACKGROUND: Despite the acclaimed beneficial effects of Telfaria occidentalis (TO), it is yet to be established that its aqueous extract is safe in the condition of renal impairment. Thus, the study investigated the effects of TO aqueous leaves extract on gentamycin-induced renal damage. METHODS: The animals were distributed into five groups. Group A (control) was placed on standard rat feed. Groups B and C received 500 mg/kg and 80 mg/kg of TO and gentamicin for 21 days, respectively. Group D received 500 mg/kg of TO 14 days before 7 days administration of 80 mg/kg of gentamycin. Group E received 80 mg/kg of gentamicin for 14 days before 7 days administration of 500 mg/kg TO. Group F received 500 mg/kg of TO and 80mg/kg of gentamycin concurrently for 21 days. Biochemical and histological examinations were analysed by standard methods. RESULTS: The administration of TO for 7 days after 14 days of gentamycin injection and its concomitant administration with gentamicin for 21 days caused significant reduction (p<0.05) on the relative kidney weight, creatinine and uric acid levels compared to groups C and D. There was a significant decrease (p<0.05) in the mean serum potassium level in group C compared to groups A, B, D, and F. The histological reports showed that the combination of the extract and gentamycin (group F) seems to ameliorate the deleterious effect observed when gentamycin was administered alone. CONCLUSIONS: The administration of the extract together with and after the administration of gentamycin reverses renal damage caused by gentamycin. PMID- 27658144 TI - Seasonal variation of gastroprotective terpenoids in Maytenus robusta (Celastraceae) quantified by gas chromatography-flame ionization detection (GC FID). AB - The triterpenes friedelin (1), beta-friedelinol (2) and 3,15-dioxo-21alpha hydroxyfriedelane (3) in the aerial parts of Maytenus robusta, a Brazilian medicinal plant with antiulcer potential, were seasonally quantified by gas chromatography flame-ionization detection (GC-FID) using an external standard. The method was found to be linear, precise and sensitive. Compounds 1 and 2 were found in M. robusta leaves and branches, with highest concentrations in the leaves collected in autumn, i.e. 3.21 +/- 0.16 and 12.60 +/- 1.49 mg g-1 dry weight of 1 and 2, respectively. On the other hand, compound 3 was found only in the branches, with the highest concentrations in winter and autumn (0.21 +/- 0.01 and 0.20 +/- 0.02 mg g-1). The results allow to define the optimal season and plant parts for the collection of M. robusta as a phytotherapeutic drug. PMID- 27658145 TI - Aspernolides L and M, new butyrolactones from the endophytic fungus Aspergillus versicolor. AB - During the systematic search of active compounds from endophytic fungi, two new butyrolactones, namely aspernolides L (2) and M (4), together with four known compounds: 1-O-acetylglycerol (1), butyrolactone I (3), butyrolactone VI (5), and (+) alantrypinone (6) were characterized from the EtOAc extract of the endophytic fungus Aspergillus versicolor isolated from the roots of Pulicaria crispa (Asteraceae). Extensive spectroscopic analysis, including 1D, 2D NMR, and HRESIMS, was used to elucidate their structures. Compounds 1, 5, and 6 are reported for the first time from this fungus. PMID- 27658146 TI - Evaluation of the hypochromic erythrocyte and reticulocyte hemoglobin content provided by the Sysmex XE-5000 analyzer in diagnosis of iron deficiency erythropoiesis. AB - BACKGROUND: Iron deficiency represents the most frequent cause of anemia. To diagnose iron deficiency some biochemical tests such as serum ferritin and the transferring saturation percent (TSAT%) are usually used. Recently, some hematological parameters such as mean reticulocyte hemoglobin content (CHr or Ret He) and percentage of hypochromic RBCs (Hypo% or %Hypo-He) were proposed as alternative to biochemical tests. In this study, the analytic performance and the diagnostic efficiency of these two parameters provided by Sysmex XE5000 analyzer on iron deficiency patients with or without anemia (IDA and ID, respectively) were evaluated. METHODS: One hundred and sixty-four healthy adults, 58 with IDA, 21 with iron depleted stores (ID), 23 with beta-thalassemia trait, and 24 with non iron deficiency anemia were selected. The gold standard used to define iron deficiency was the coexistence of serum ferritin below 15 MUg/L (12 in women) and TSAT <16%. RESULTS: For %Hypo-He, the best cut-off value for both IDA and ID is 0.9% while for Ret-He is 30.6 pg. For both parameters the performance was better to diagnose IDA (AUC, 0.96 and 0.98) than ID (AUC, 0.93 and 0.95). The Ret-He behavior was always slightly better than that of %Hypo-He. CONCLUSIONS: The use of these two parameters is useful to detect iron deficiency conditions if the hemoglobin synthesis has already been compromised. PMID- 27658147 TI - Peer groups splitting in Croatian EQA scheme: a trade-off between homogeneity and sample size number. AB - BACKGROUND: Laboratory evaluation through external quality assessment (EQA) schemes is often performed as 'peer group' comparison under the assumption that matrix effects influence the comparisons between results of different methods, for analytes where no commutable materials with reference value assignment are available. With EQA schemes that are not large but have many available instruments and reagent options for same analyte, homogenous peer groups must be created with adequate number of results to enable satisfactory statistical evaluation. We proposed a multivariate analysis of variance (MANOVA)-based test to evaluate heterogeneity of peer groups within the Croatian EQA biochemistry scheme and identify groups where further splitting might improve laboratory evaluation. METHODS: EQA biochemistry results were divided according to instruments used per analyte and the MANOVA test was used to verify statistically significant differences between subgroups. The number of samples was determined by sample size calculation ensuring a power of 90% and allowing the false flagging rate to increase not more than 5%. When statistically significant differences between subgroups were found, clear improvement of laboratory evaluation was assessed before splitting groups. RESULTS: After evaluating 29 peer groups, we found strong evidence for further splitting of six groups. Overall improvement of 6% reported results were observed, with the percentage being as high as 27.4% for one particular method. CONCLUSIONS: Defining maximal allowable differences between subgroups based on flagging rate change, followed by sample size planning and MANOVA, identifies heterogeneous peer groups where further splitting improves laboratory evaluation and enables continuous monitoring for peer group heterogeneity within EQA schemes. PMID- 27658148 TI - Performance of point-of-care HbA1c test devices: implications for use in clinical practice - a systematic review and meta-analysis. AB - BACKGROUND: Point-of-care (POC) devices could be used to measure hemoglobin A1c (HbA1c) in the doctors' office, allowing immediate feedback of results to patients. Reports have raised concerns about the analytical performance of some of these devices. We carried out a systematic review and meta-analysis using a novel approach to compare the accuracy and precision of POC HbA1c devices. METHODS: Medline, Embase and Web of Science databases were searched in June 2015 for published reports comparing POC HbA1c devices with laboratory methods. Two reviewers screened articles and extracted data on bias, precision and diagnostic accuracy. Mean bias and variability between the POC and laboratory test were combined in a meta-analysis. Study quality was assessed using the QUADAS2 tool. RESULTS: Two researchers independently reviewed 1739 records for eligibility. Sixty-one studies were included in the meta-analysis of mean bias. Devices evaluated were A1cgear, A1cNow, Afinion, B-analyst, Clover, Cobas b101, DCA 2000/Vantage, HemoCue, Innovastar, Nycocard, Quo-Lab, Quo-Test and SDA1cCare. Nine devices had a negative mean bias which was significant for three devices. There was substantial variability in bias within devices. There was no difference in bias between clinical or laboratory operators in two devices. CONCLUSIONS: This is the first meta-analysis to directly compare performance of POC HbA1c devices. Use of a device with a mean negative bias compared to a laboratory method may lead to higher levels of glycemia and a lower risk of hypoglycaemia. The implications of this on clinical decision-making and patient outcomes now need to be tested in a randomized trial. PMID- 27658149 TI - P35 and P22 Toxoplasma gondii antigens abbreviate regions to diagnose acquired toxoplasmosis during pregnancy: toward single-sample assays. AB - BACKGROUND: P35 and P22 Toxoplasma gondii proteins are recognized by specific IgG at the early infection stage, making them ideal for acute toxoplasmosis pregnancy control. Both proteins have been studied to discriminate between acute and chronic toxoplasmosis. However, results were hardly comparable because different protein obtainment procedures led to different antigens, the reference panels used were not optimally typified, and avidity tests were either not performed or narrowly examined. METHODS: We bioinformatically predicted P35 and P22 regions with the highest density of epitopes, and expressed them in pET32/BL21DE3 alternative expression system, obtaining the soluble proteins rP35a and rP22a. We assessed their diagnostic performance using pregnant woman serum samples typified as: not infected, NI (IgG-, IgM-), typical-chronic, TC (IgM-, IgG+), presumably acute, A (IgG+, IgM+, low-avidity IgG), and recently chronic, RC (IgG+, IgM+, high-avidity IgG). RESULTS: rP35a performed better than rP22a to differentiate A from RC, the areas under the curve (AUC) being 0.911 and 0.818, respectively. They, however, performed similarly to differentiate A from TC+RC (AUC: 0.915 and 0.907, respectively). rP35a and rP22a evaluation by avidity ELISA to discriminate A from RC rendered AUC values of 0.974 and 0.921, respectively. The indirect ELISA and avidity ELISA results analyzed in tandem were consistent with those obtained using commercial kits. CONCLUSIONS: rP35a and rP22a features suggest that, with complementary use, they could replace parasite lysate for toxoplasmosis infection screening and for acute toxoplasmosis diagnosis. Our proposal should be validated by a longitudinal study and may lead to a reliable toxoplasmosis pregnancy control, performing tests in only one serum sample. PMID- 27658150 TI - Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a Chinese hospital system perspective. AB - BACKGROUND: Cost-impact models have indicated that in the USA, the use of antibiotic stewardship protocols based on procalcitonin (PCT) levels for patients with suspected acute respiratory tract infection results in cost savings. Our objective was to assess the cost impact of adopting PCT testing among patients with acute respiratory infections (ARI) from the perspective of a typical hospital system in urban China. METHODS: To conduct an economic evaluation of PCT testing versus usual care we built a cost-impact model based on a previously published patient-level meta-analysis data of randomized trials including Chinese sites. The data were adapted to the China setting by applying the results to mean lengths of stay, costs, and practice patterns typically found in China. We estimated the annual ARI visit rate for the typical hospital system (assumed to be 1650 beds) and ARI diagnosis. RESULTS: In the inpatient setting, the costs of PCT-guided care compared to usual care for a cohort of 16,405 confirmed ARI patients was almost 1.1 million Chinese yuan (CNY), compared to almost 1.8 million CNY for usual care, resulting in net savings of 721,563 CNY to a typical urban Chinese hospital system for 2015. In the ICU and outpatient settings, savings were 250,699 CNY and 2.4 million CNY, respectively. The overall annual net savings of PCT-guided care was nearly 3.4 million CNY. CONCLUSIONS: Substantial savings are associated with PCT protocols of ARI across common China hospital treatment settings mainly by direct reduction in unnecessary antibiotic utilization. PMID- 27658151 TI - Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years' experience. AB - BACKGROUND: Preanalytical variables, such as sample collection, handling and transport, may affect patient results. Preanalytical phase quality monitoring should be established in order to minimize laboratory errors and improve patient safety. METHODS: A retrospective study (2001-2013) of the results obtained through the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) External quality assessment (preanalytical phase) was performed to summarize data regarding the main factors affecting preanalytical phase quality. Our aim was to compare data from 2006 to 2013 with a previously published manuscript assessing the 2001-2005 period. RESULTS: A significant decrease in rejection rates was observed both for blood and urine samples. For serum samples, the most frequent rejection causes in the first period were non-received samples (37.5%), hemolysis (29.3%) and clotted samples (14.4%). Conversely, in the second period, hemolysis was the main rejection cause (36.2%), followed by non-received samples (34.5%) and clotted samples (11.1%). For urine samples, the main rejection cause overall was a non-received sample (up to 86.1% of cases in the second period, and 81.6% in the first). For blood samples with anticoagulant, the number of rejections also decreased. While plasma-citrate-ESR still showed the highest percentages of rejections (0.980% vs. 1.473%, p<0.001), the lowest corresponded to whole-blood EDTA (0.296% vs. 0.381%, p<0.001). CONCLUSIONS: For the majority of sample types, a decrease in preanalytical errors was confirmed. Improvements in organization, implementation of standardized procedures in the preanalytical phase, and participation in a Spanish external quality assessment scheme may have notably contributed to error reduction in this phase. PMID- 27658152 TI - A real-world evidence-based approach to laboratory reorganization using e-Valuate benchmarking data. AB - BACKGROUND: Pressure to cut health-care costs has involved clinical laboratories underpinning the need to reduce cost per test through programs designed to consolidate activities and increase volumes. Currently, however, there is little evidence of the effectiveness of these measures. The aim of the present study was to verify whether a rational, evidence-based decision-making process might be achieved based on an activity-based cost analysis performed by collecting the data of all variables affecting cost per test. METHODS: An activity-based costing analysis was performed using a program that provides collected data on performance indicators, benchmark between different laboratories based on performance indicators, and information on reorganization initiatives. RESULTS: The data provided were used in two different settings to (1) verify the results of the internal re-organization of specific protein assay and (2) simulate some scenarios for the reorganization of autoimmune testing in the network of clinical laboratories in a large territory. CONCLUSIONS: The data produced by the e Valuate project enabled the quantification of variation in costs, the utilization of human and technological resources and efficiency, both as final result of a reorganization project (proteins) and as a simulation of a possible future organization (autoimmune tests). PMID- 27658153 TI - Retrospective validation of a beta-trace protein interpretation algorithm for the diagnosis of cerebrospinal fluid leakage. AB - BACKGROUND: Cerebrospinal fluid (CSF) leakage is a rare condition that can potentially lead to the development of serious complications. In the last decade, beta-trace protein (beta-TP) has been shown to be a valuable immunological biomarker that allows prompt and non-invasive identification of CSF leakage. At our institution, the measurement of beta-TP has been included in the diagnostic work-up of CSF leakage for more than 10 years. According to our diagnostic algorithm, the presence of CSF in secretion is excluded when beta-TP values are <0.7 mg/L, whereas beta-TP values >=1.3 mg/L indicate the presence of CSF in secretion. beta-TP values between 0.7 and 1.29 mg/L indicate the presence of CSF if the beta-TP ratio (beta-TP secretion/beta-TP serum) is >=2. This study aimed to validate this diagnostic algorithm using clinically defined nasal/ear secretions. METHODS: We performed a retrospective statistical analysis of three beta-TP interpretation strategies using data of 236 samples originating from 121 patients with suspect CSF leakage received at our laboratory between 2004 and 2012. RESULTS: The highest odds ratio was obtained when the proposed algorithm has been used for the interpretation of beta-TP results, showing a sensitivity of 98.3% and a specificity of 96%. Positive and negative predictive values were 89.2% and 99.4%, respectively. CONCLUSIONS: Our data suggest that the proposed beta-TP interpretation algorithm is a valuable tool for the diagnosis of CSF leakage in the clinical practice. PMID- 27658154 TI - Interference of laboratory disinfection with trichloro-isocyanuric acid on cardiac troponin I measurement using the Vitros immunoassay system. PMID- 27658155 TI - Deciphering a macro-troponin I complex; a case report. PMID- 27658156 TI - Fecal calprotectin in inflammatory bowel diseases: update and perspectives. AB - Inflammatory bowel diseases (IBDs) are chronic diseases that result from the inflammation of the intestinal wall, suspected in any patient presenting with intestinal symptoms. Until recently, the diagnosis was mainly based on both clinical and endoscopic arguments. The use of an easy, fast, reliable, non invasive, and inexpensive biological assay is mandatory not only in diagnosis but also in evolutionary and therapeutic monitoring. To date, the fecal calprotectin is the most documented in this perspective. This marker allows the discrimination between functional and organic bowel processes with good performance. The determination of the fecal calprotectin level contributes to the evaluation of the degree of disease activity and to monitoring of therapeutic response. PMID- 27658157 TI - Clinical autoantibody detection by microarray. AB - BACKGROUND: AMiDot is a microdot array-based immunoassay that allows simultaneous detection of multiple autoantibodies on a single patient. We evaluated the AMiDot "Systemic Autoimmune Disease" (SAD) panel, which detects antibodies to 17 different antigens. METHODS: AMiDot was performed on 184 samples from blood donors and on 280 randomly selected clinical samples containing antibodies to extractable nuclear antigens or to dsDNA. The results obtained by AMiDot on the clinical samples were compared to results obtained by EliA (Thermo Fisher) for anti-Ro60, anti-La, anti-RNP, anti-Scl-70, anti-CENPB, anti-Sm, and anti-Jo-1 and by Farr assay for anti-dsDNA. Discordant results were further analyzed by immunodot (D-tek). RESULTS: Concordance between AMiDot and EliA was >=87% and kappa agreement >=0.44. When compared to EliA and immunodot (in case of discordance between AMiDot and EliA), concordance improved to >=91% and kappa agreement to >=0.77. The sensitivity of AMiDot (compared to EliA and immunodot, in case of discordance between AMiDot and EliA) was >=93%, except for anti-Ro60 (84%). The concordance and kappa agreement of AMiDot with the Farr assay (for dsDNA antibodies) was, respectively, 84% and 0.33. The sensitivity of AMiDot for dsDNA (compared to Farr assay) was 25%. The specificity was >=97% (in blood donors as well as in clinical samples). The within-run imprecision was 9%-27% and the between-run imprecision 29%-39%. CONCLUSIONS: AMiDot offers an alternative to line immunodot assay. Individual antibody assays might suffer from low sensitivity. PMID- 27658158 TI - Improving Gram stain proficiency in hospital and satellite laboratories that do not have microbiology. AB - BACKGROUND: Consolidation of laboratories has left many hospitals and satellite laboratories with minimal microbiologic testing. In many hospitals and satellite laboratories, Gram stains on primary specimens are still performed despite difficultly in maintaining proficiency. METHODS: To maintain Gram stain proficiency at a community 450-bed hospital with an active emergency room we designed bimonthly challenges that require reporting Gram staining and morphology of different organisms. The challenges consist of five specimens prepared by the reference microbiology laboratory from cultures and primary specimens. Twenty to 23 medical laboratory scientists participate reading the challenges. Results from the challenges are discussed with each medical laboratory scientists. In addition, printed images from the challenges are presented at huddle to add microbiology knowledge. RESULTS: On the first three challenges, Gram staining was read correctly in 71%-77% of the time while morphology 53%-66%. In the last six challenges correct answers for Gram stain were 77%-99% while morphology 73%-96%. CONCLUSIONS: We observed statistically significant improvement when reading Gram stains by providing frequent challenges to medical laboratory scientists. The clinical importance of Gram stain results is emphasized during huddle presentations increasing knowledge and motivation to perform the test for patients. PMID- 27658160 TI - In defense of aldosterone measurement by immunoassay: a broader perspective. PMID- 27658159 TI - Evaluation of the accuracy of the Greiner Bio-One FC Mix Glucose tube. PMID- 27658161 TI - Hepatorenal Syndrome: Diagnosis and Treatment - newsreel. AB - Hepatorenal syndrome (HRS) is defined as renal failure that occurs in the presence of severe acute or chronic liver disease in the absence of underlying renal pathology. Due to the functional nature of the disease and the absence of specific diagnostic markers, HRS diagnosis is determined based on positive criteria associated with excluding other causes of renal failure in patients with liver cirrhosis and ascites. Differentiation from other types of acute or chronic renal disease is extremely difficult and therapeutic options are limited, prophylactic behavior is most appropriate in patients with severe hepatic disease and risk factors for the installation of hepatorenal syndrome. Highlighting all precipitating factors of acute renal insufficiency and therapeutic modalities in order to minimize adverse events is an important step in improving the follow-up of the patients with liver cirrhosis. The prognosis is reserved especially for type 1 HRS. Liver transplantation is the best option for patients without contraindications. The therapies introduced in recent years, such as vasoconstrictor drugs or transjugular intrahepatic portosystemic shunt are effective methods in the renal function improvement. PMID- 27658162 TI - Helicobacter pylori Infection, Gastric Cancer and Gastropanel. AB - Gastric cancer (GC) is one of the most widespread types of cancer worldwide. Helicobacter pylori infection has been clearly correlated with gastric carcinogenesis. At present and in the near future, the most important challenge is and will be the significant reduction of mortality due to GC. That goal can be achieved through the identification of higher-risk patients, such as those with atrophic gastritis, intestinal metaplasia and dysplasia. In this review we intend to discuss the importance of diagnosing H. pylori infection and chronic atrophic gastritis in preventing gastric cancer, using a new non-invasive test called GastroPanel. This test is a classification algorithm including four biochemical parameters pepsinogen I and II (PGI and PGII), gastrin-17 (G17), and anti Helicobacter pylori antibodies (Ig G anti-Hp) measured in fasting sera, which allows to classify patients as having atrophic or non-atrophic gastritis and to find whether gastritis is associated or not with H. pylori infection. GastroPanel is not a "cancer test", but it can and should be used in the screening and diagnosis of subjects with a high cancer risk; still, a careful diagnostic made by superior digestive endoscopy is compulsory to find possible precancerous or cancerous lesions at an early and curable stage. PMID- 27658163 TI - Proceedings from the 1st Insights in Hematology Symposium, Cluj-Napoca, Romania March 11-12, 2016. AB - In the March 2016 issue of the Lancet Haematology, the editorial office published a paper stating the roadmap for European research in hematology, based on the European Hematology Association (EHA) consensus document that outlines the directions in hematology for the following years across the continent. The meeting entitled "Insights in hematology" is organized a support for the initiative of a roadmap for European hematologists regarding research, may it be basic research or clinical research, but this consensus should not be focused mainly on European institutions, but rather form the backbone of global research between Europe and the United States, Japan or any other country. This will allow Europeans to learn as well as to share their experience with the rest of the scientific and medical community. And the Cluj-Napoca meeting should be followed by other such meetings all across the EU. PMID- 27658164 TI - Cardiac Changes in Overweight and Obese Patients. AB - BACKGROUND: Obesity and overweight are two pathologies that are more and more frequent in the XXIst century diagnosis and are causing high morbidity and mortality rates in the general population, especially through cardiovascular complications. AIMS: Identification and early diagnosis of cardiac changes in overweight and obese patients. MATERIAL AND METHOD: We carried out a sectional, analytical and observational study on 111 subjects: 27 normal weight subjects and 84 overweight and obese patients, which were submitted to a clinical exam, biochemical exams and 2D ultrasound. RESULTS: The presence of diastolic dysfunction is twice more frequent in overweight patients in comparison to normal weight ones (30% vs 15%) and 5 times more frequent in obese patients than normal weight ones (75% vs 15%). The size increase of the interventricular septum is correlated with the body mass index, there being statistically significant differences between normal weight vs overweight vs obese patients, as well as between overweight and obese ones. Within the whole group and within the groups, both the left ventricle mass (g) as well as the left ventricle mass to body surface ratio (g/m2) are statistically significantly higher in patients with present diastolic dysfunction (E/A < 1). This indicates a relation between the presence of diastolic dysfunction, increased left ventricle mass and body mass index (p < 0.05). CONCLUSIONS: Overweight and obese patients, unlike normal weight ones, present early cardiac changes, such as: a decrease of left ventricle ejection fraction, diastolic dysfunction, thickening of the interventricular septum, increase of the left ventricle mass both per se as well as in ratio to body surface. PMID- 27658166 TI - Cytology of Pericardial Effusion due to Malignancy. AB - BACKGROUND: Malignant pericardial effusion occurs in one tenth of all cancers. It is a very serious disorder that is mainly a secondary process due to metastasis because primary neoplasms of the pericardium such as mesotheliomas, sarcomas being exceedingly rare [corrected]. Pericardial effusion specimens are uncommon and to the best of our knowledge the current study is the largest systematic evaluation of pericardial fluid cytology performed to date. MATERIAL AND METHODS: Pericardial effusion specimens from 145 patients collected over a 25 [corrected] year period were studied by cytology [corrected]. The minimum pericardial fluid volume used for adequate cytologic diagnosis in these patients was more than 60 mL. RESULTS: Cytological diagnosis revealed malignant pericardial exudates in 100% of the studied patients [corrected]. CONCLUSIONS: Cytology provides an immediate and accurate means of diagnosis. Immunocytology is very importantin the diagnostic evaluation. PMID- 27658165 TI - The Etiology of Syncope in an Emergency Hospital. AB - BACKGROUND: Syncope is a commonly encountered problem in an emergency hospital. Global cerebral hypoperfusion is the final pathway common to all presentations of syncope, but this symptom presentation has a broad differential diagnosis. It is important to identify patients for whom syncope is a symptom of a potentially life-threatening condition. MATERIAL AND METHODS: We identified adult patients presenting with syncope to the Emergency Department of our hospital from January 2012 to June 2014. Of 590 patients found in the hospital database we further selected 217 patients who met our criteria, namely having a positive diagnosis of syncope (being clearly distinguished from other TLOCs) and an etiology of the disease. Thus, definite diagnosis was established retrospectively by reviewing medical records. RESULTS: The demographics of our group shows a slightly different distribution between men and women (49% men and 51% women) and a majority of the urban population (67%). As for the age range, most of our patients were in the age group of 70-80 years (30%), 29% were > 80 years old, and the percentage decreases significantly in the 60-70 years range (17%). The most frequent causes of syncope were cardiac (32%), vasovagal (23%) and due to orthostatic hypotension (12%), but we have also found various cases of mixt or iatrogenic causes. CONCLUSIONS: The incidence of syncope increases sharply after 70 years of age and poses special consideration in light of multiple comorbid conditions, age-related changes, atypical presentation, and concomitant medication use. The most common causes of syncope in this population are cardiac causes, orthostatic hypotension and carotid sinus hypersensitivity. Often, root cause of syncope remains undiagnosed, despite exhaustive diagnostic testing. PMID- 27658167 TI - Cinacalcet versus Parathyroidectomy in the Treatment of Secondary Hyperparathyroidism Post Renal Transplantation. AB - BACKGROUND: Persistent hyperparathyroidism (HPT) with hypercalcemia is prevalent after transplant and is considered a risk factor for progressive bone loss and fractures and vascular calcification, as well as the development of tubulointerstitial calcifications of renal allografts and graft dysfunction. The subtotal parathyroidectomy is the standard treatment, although currently it has been replaced by the calcimimetic cinacalcet. AIM: The hypothesis of this study is that subtotal parathyroidectomy is superior to cinacalcet for treatment of persistent secondary parathyroidectomy post renal transplant, with minimal morbidity and significantly it reduces the cost of treatment after transplantation. METHODS: We report our long-term clinical experience with either cinacalcet or parathyroidectomy in 59 kidney transplant recipients with hyperparathyroidism. Group one included medical treatment with cinacalcet and had 45 patients while parathyroidectomy patients (group 2) were 16 patients with two of them excluded because of surgical failure. RESULTS: No difference was found between groups for any parameter. A greater short-term change of calcium and phosphorus homeostasis obtained by surgery than by cinacalcet, and in long term change, no significant difference between the two groups. CONCLUSIONS: The main findings of this study are that correction of severe hyperparathyroidism was similar in both surgical and cinacalcet groups with the absence of a difference of long-term serum iPTH 1-84 levels between the two groups. PMID- 27658168 TI - Primary Hyperfibrinolysis as a Presentation of Extended Prostate Carcinoma. AB - Primary hyperfibrinolysis States are rare entities associated with different clinical scenarios and can be sometimes their first presentation. PHS outcome relies on the underlying cause. We introduce the case of a man presenting with a complex clotting abnormality malignancy related. Not having an accurate diagnosis hindered us to give an easy solution and compromised the prognosis overall. Misdiagnosing a severe entity often leads to fatal outcomes. We want to highlight the rarity of our case, the challenging differential diagnosis and the importance of being aware of PHS. Because our patient appeared to have an extended carcinoma, definitive treatment was not an option on our case.When an uncommon and challenging disease is presented, having all the clues is mandatory to succeed. PMID- 27658169 TI - First Successful Haploidentical Stem Cell Transplantation in Romania. AB - Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a premiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe. PMID- 27658170 TI - Corrigendum to: Porojan M., Costin S., Poanta L., Cerghizan A., Pop D., Dumitrascu D.L., Autonomic Neuropathy and Plasma Catecholamine in patients with Diabetes Mellitus. PMID- 27658171 TI - Effect of limonene on the heterotrophic growth and polyhydroxybutyrate production by Cupriavidus necator H16. AB - The inhibitory effect of limonene on polyhydroxybutyrate (PHB) production in Cupriavidus necator H16 was studied. Firstly, results demonstrate the feasibility of using orange juicing waste (OJW) as a substrate for PHB production. An intracellular PHB content of 81.4% (w/w) was attained for a total dry matter concentration of 9.58gL-1, when the OJW medium was used. Later, a mineral medium designed to mimic the nutrient levels found in the complex medium derived from OJW was used to study the effect of limonene on the production of PHB. Results showed a drop in specific growth rate (MU) of more than 50% when the initial limonene concentration was 2% (v/v) compared to the limonene free medium. This work highlights the importance of a limonene recovery stage prior to fermentation, to maintain levels below 1% (v/v) in the medium, adding value to the OJW and enhancing the fermentation process productivity. PMID- 27658172 TI - Biodiesel production from wet microalgae by using graphene oxide as solid acid catalyst. AB - In order to produce biodiesel from lipids in wet microalgae with graphene oxide (GO) as solid acid catalyst, the effects on lipids conversion efficiencies of catalyst dosage, transesterification temperature, reaction time, methanol dosage and chloroform dosage were investigated. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and elemental analysis revealed that GO contained 0.997mmol SO3H groups per gram and high amounts of OH groups. Scanning electron microscopy showed that wet microalgae cells were adsorbed on hydrophilic GO surfaces covered with many OH groups. Lipids extracted by chloroform from microalgal cells were transformed into fatty acids methyl esters (FAMEs) through transesterification catalyzed by the acid centers (SO3H groups) in GO catalysts. The lipids conversion efficiency into FAMEs was 95.1% in microwave-assisted transesterification reactions of 5wt.% GO catalyst at 90 degrees C for 40min. PMID- 27658173 TI - Nitrate removal and bioenergy production in constructed wetland coupled with microbial fuel cell: Establishment of electrochemically active bacteria community on anode. AB - The constructed wetland coupled with microbial fuel cell (CW-MFC) systems operated at different substrate concentration and pH influents were evaluated for bioelectricity generation, contaminant removal and microbial community structure. Performance of CW-MFC was evaluated at organic loading rate of 75.3gCODm-3d-1 and pH gradients of (5.18+/-0.14, 7.31+/-0.13, and 8.75+/-0.12) using carbon fiber felt as electrodes. Peak power density was observed at slightly neutral influent condition. Compared with the open circuit CW-MFC, average COD and NO3-N removal efficiency in CW-MFC increased by 8.3% and 40.2% respectively under slightly neutral pH of influents. However, the removal efficiency and bioenergy production have been inhibited with acidic influents. The relative abundance of beta Proteobacteria, nitrobacteria and denitrifying bacteria was significantly promoted in closed-circuit CW-MFC. Using of CW-MFC as a biochemical method for nitrate removal and bioelectricity generation under slightly neutral and alkaline influent conditions was a promising technology. PMID- 27658174 TI - An auto-inducible Escherichia coli strain obtained by adaptive laboratory evolution for fatty acid synthesis from ionic liquid-treated bamboo hydrolysate. AB - Adaptive laboratory evolution (ALE) is a useful metabolic engineering strategy, which allows the selection of the microorganisms with beneficial phenotype through accumulative beneficial mutations among genetic variations occurrencely. Following ALE strategy, a rational constructed Escherichia coli strain DQ101 for fatty acids synthesis was adaptively evolved for 90days with increasing [C4mim]Cl concentration from 1% to 7% (w/v). The evolved strain DQ102 reached a final OD600 of 4.93 at the end of the 24h culture with 7% (w/v) ionic liquid. DQ102/pDQTES with a thioesterase 'TesA overexpression could produce 1.12g/L fatty acid with a productivity of 0.023g/L-h from ionic liquid-treated bamboo hydrolysate. With another beta-hydroxyacyl-ACP dehydratases (fabZ) overexpression, DQ102/pDQTESZ could reach a higher concentration of 2.29g/L with a productivity of 0.048g/L-h. These results indicated that ALE could be implemented as a useful tool for metabolic engineering and production of bio-fuels, as well as commodity and specialty chemicals. PMID- 27658176 TI - Die Macht des Wortes. PMID- 27658177 TI - Erratum: Vol. 65, No. 35. AB - In the report, "Community Needs Assessment After Microcystin Toxin Contamination of a Municipal Water Supply - Lucas County, Ohio, September 2014," the first footnote on page 928 should be, "* https://www.epa.gov/sites/production/files/2015-06/documents/microcystins-report 2015.pdf." PMID- 27658175 TI - Testing and referral patterns in the years surrounding the US Preventive Services Task Force recommendation against prostate-specific antigen screening. AB - BACKGROUND: Since the US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening, there have been conflicting reports regarding the impact on the behavior of providers. This study analyzed real-world data on PSA ordering and referral practices in the years surrounding the recommendation. METHODS: A whole-institution sample of entered PSA orders and urology referrals was obtained from the electronic medical record. The study was performed at a tertiary referral center with a catchment in the southern United States. PSA examinations were defined as screening when they were ordered by providers with appointments in internal medicine, family medicine, or general internal medicine. Linear and quadratic regression analyses were performed, and joinpoint regression was used to assess for trend inflection points. RESULTS: Between January 2010 and July 2015, there were 275,784 unique ambulatory visits for men. There were 63,722 raw PSA orders, and 54,684 were evaluable. Primary care providers ordered 17,315 PSA tests and 858 urology referrals. The number of PSA tests per ambulatory visit, the number of referrals per ambulatory visit, the age at the time of the urology referral, and the proportion of PSA tests performed outside the recommended age range did not significantly change. The PSA value at the time of referral increased significantly (P = .022). Joinpoint analysis revealed no joinpoints in the analysis of total PSA orders, screening PSA tests, or examinations per 100 visits. CONCLUSIONS: In the years surrounding the USPSTF recommendation, PSA behavior did not change significantly. Patients were referred at progressively higher average PSA levels. The implications for prostate cancer outcomes from these trends warrant further research into provider variables associated with actual PSA utilization. Cancer 2016;122:3785-3793. (c) 2016 American Cancer Society. PMID- 27658178 TI - Delays in Sound Recognition and Imitation in Underinsured Children Receiving Cochlear Implantation. AB - Importance: Barriers to early pediatric cochlear implantation in underinsured populations have been previously reported. However, to our knowledge, the effect of this delay on the development of auditory and speech-language objectives has not been evaluated. Objective: To determine if health care insurance status affects the achievement of proficiency in basic sound access and imitation tasks in children with cochlear implants. Design, Setting, and Participants: A retrospective review of 123 children aged 1 to 12 years receiving cochlear implants at the single tertiary referral academic free-standing Children's National Health System in Washington, DC, between January 1, 2008, and December 31, 2015. Main Outcomes and Measures: Auditory function after cochlear implantation, time to proficiency in Ling-6 scores, and number of speech therapy and audiological appointments, as well as current educational setting, were compared with patient age at diagnosis of hearing loss, age at cochlear implantation, cochlear implantation insertion technique, and health care insurance status for recipients of cochlear implants. Results: A total of 123 children aged 1 to 12 years (mean [SD] age, 64.0 [57.4] years) with cochlear implants were included in the study. Of 37 patients with complete and accurate Ling-6 test scores, 23 (62.1%) were able to have proficiency a mean of 5.1 months at follow-up. Despite equal auditory performance on pure-tone audiometry after cochlear implantation, publicly insured recipients had Ling-6 proficiency a mean of 6.0 months (95% CI, 5.5-6.5 months) later than privately insured recipients (11.0 vs 5.0 months). When controlling for patient age, time to cochlear implantation, number of therapy sessions, and cochlear implantation insertion technique, multivariable logistic regression analysis revealed health care insurance status to be the independent variable associated with inadequate Ling-6 discrimination scores (odds ratio, 46.2; 95% CI, 2.9-729.4). Conclusions and Relevance: Despite equal speech detection scores, publicly insured recipients of cochlear implantation had a significant and critical delay in attaining proficiency in a fundamental measure of sound recognition and imitation. PMID- 27658179 TI - Highlights in Central Nervous System Tumors. PMID- 27658180 TI - Human papillomavirus vaccination in men who have sex with men - what will be required by 2020 for the same dramatic changes seen in heterosexuals. AB - This paper addresses the issue of whether men who have sex with men (MSM) will share the spectacular reductions in human papillomavirus (HPV) infection and its associated neoplasia that we are currently witnessing in heterosexuals. The reproductive rate for HPV infection in heterosexuals is not well established, but 70% vaccination coverage in women has resulted in a fall of more than 90% in genital warts and HPV types 16/18 in young women and 80% fall in young men indicating that the critical vaccination threshold has been exceeded for this group. Published data on the three elements of the reproductive rate for HPV infection (i.e. transmission probability per sexual partnership, rate of partner change and duration of infectiousness) suggest they are higher in MSM than heterosexuals. This indicates that the reproductive rate for HPV will be higher in MSM and hence the critical vaccination threshold will also be higher. But while vaccinating 70% of girls protect 70% of sexual partnerships in heterosexuals, vaccinating 70% of boys protect more than 70% of partnerships in MSM. Only 9% (30% by 30%) of sexual partnerships in MSM are not protected with 70% coverage. Therefore vaccinating 70% of boys will protect 91% of sexual partnerships in MSM. However the efficacy of the HPV vaccine is much lower when sexually active MSM are vaccinated rather than boys. We argue that if MSM are to have the same benefit from the HPV vaccine that heterosexuals had, boys and not adult MSM will need to be vaccinated. PMID- 27658181 TI - Hemiepiphysiodesis for Idiopathic Genu Valgum: Percutaneous Transphyseal Screw Versus Tension-band Plate. AB - BACKGROUND: The aim of this study was to compare the outcomes of angular deformity correction by percutaneous hemiepiphysiodesis using transphyseal screw (PETS) or tension-band plating (TBP) in growing children with idiopathic genu valgum with emphasis on the rate of deformity correction. METHODS: We retrospectively reviewed cases of hemiepiphysiodesis for angular deformity in lower extremities between 2009 and 2014. A total of 90 limbs in 33 patients received PETS and 60 limbs in 24 patients received TBP. Angular measurements were compared preoperatively and at the time of hardware removal. The amount and rate of angular deformity correction were compared between the 2 groups. Potential factors affecting correction velocity were investigated using multivariate analysis. RESULTS: Angular correction was achieved in all patients. The mean rate of correction was more rapid with PETS than with TBP at both the distal femur (0.92 vs. 0.64 deg./mo, respectively; P<0.001) and proximal tibia (0.72 vs. 0.55 deg./mo, respectively; P=0.019). Multivariate analysis showed that the used implant significantly affected the rate of correction: PETS demonstrated faster correction velocity than TBP (-0.26, 95% confidence interval, -0.35 to -0.17, P<0.001). CONCLUSIONS: Both PETS and TBP techniques result in satisfactory correction of coronal angular deformity in patients with idiopathic genu valgum. However, the observed rate of correction was faster with PETS than TBP. Correction with PETS, rather than TBP, may better serve patients near skeletal maturity. LEVEL OF EVIDENCE: Level III-retrospective comparative series. PMID- 27658182 TI - Are respiratory viruses involved in preseasonal symptoms or severity in Japanese cedar pollinosis? AB - BACKGROUND: Respiratory virus infections are involved in asthma exacerbations. However, there are no reports of the relationship between respiratory virus infections and Japanese cedar pollinosis. OBJECTIVE: We studied the relationship between respiratory viral infection and the appearance of preseasonal symptoms and the severity of seasonal symptoms in Japanese cedar pollinosis. METHODS: In 36 patients with asthma and with no symptoms (PreAsyP) and 54 patients with asthma and with symptoms (PreSyP) before the cedar pollen shedding commenced (preseason), and 37 patients with mild-to-moderate severity (InMild/Mod) and 45 patients with severe to extreme severity (InSev/Ext) after cedar shedding commenced (in season), the occurrence of respiratory viruses and nasal smear cytology were examined. RESULTS: In total, seven infections with respiratory viruses were detected among the subjects. Human rhinovirus (HRV) C infection was detected in one subject in each of the PreAsyP and PreSyP groups, and one HRVA infection occurred in the InMild/Mod group. In the InSev/Ext group, one HRVA, one HRVC, one respiratory syncytial virus, and one human metapneumovirus were detected. There was no significant difference in the rate of detection of viral infections between the PreAsyP and the PreSyP groups (p = 0.077), and between the InMild/Mod group and the InSev/Ext group (p = 0.24, Wilcoxon rank sum test). When cells types in nasal smears were identified and their abundance examined, the rate of neutrophilia in the subjects in the PreSyP group was 54%, which was statistically higher (p < 0.01) than the subjects in the PreAsyP group (25%). Interestingly, in the subjects in the InSev/Ext group, the proportion of eosinophils (40%) was larger (p < 0.05) than in the subjects in the InMild/Mod group (19%). CONCLUSION: These results provided no evidence that respiratory virus infections contributed to preseasonal symptoms and severity in season of Japanese cedar pollinosis. Nasal neutrophilia was related to preseasonal symptoms, whereas nasal eosinophilia was related to severity of symptoms during the pollen season. PMID- 27658184 TI - Congenital bilateral adult choanal atresia undiagnosed until the second decade: How we did it. AB - BACKGROUND: Bilateral congenital choanal atresia that presents in adulthood is rare. There are only eight reported cases in the literature. METHOD: We present a ninth case of adult bilateral choanal atresia diagnosed at the age of 20 years. Can a bilateral choanal atresia present so late in life when such a condition is considered incompatible with life? RESULTS AND CONCLUSION: Clinical details, diagnosis, and surgical steps with a clear depiction of photographs and comparison with all other previously reported cases, which can help novel otolaryngologists in their clinical practice are discussed. PMID- 27658183 TI - Role of antioxidants on the clinical outcome of patients with perennial allergic rhinitis. AB - BACKGROUND: Antioxidants have a preventive or therapeutic role in oxygen free radical-mediated cell and tissue damage. The study aimed to investigate the therapeutic effects of antioxidants and intranasal steroid fluticasone furoate (FF) on the clinical outcome of patients with perennial allergic rhinitis. METHODS: Subjects with perennial allergic rhinitis (n = 61) were randomly divided into two groups, group A (n = 30) received FF and group B (n = 31) received FF with antioxidants for 6 weeks. Nasal and ocular symptoms were evaluated weekly by using a four-point categoric scale. The efficacy of the study drug was assessed based on the mean change from baseline of the total daytime nasal symptom scores, total nighttime nasal symptom scores, and the composite symptom scores. RESULTS: The combined therapy (FF with antioxidants) resulted in marked improvements (p <= 0.05) in the mean total daytime nasal symptom scores, total nighttime nasal symptom scores, and composite symptom scores of subjects compared with ones treated with intranasal steroid (FF) alone, which highlighted the therapeutic effect of antioxidants in allergic rhinitis. CONCLUSION: Significant improvement in clinical outcome was observed in subjects who received antioxidants along with FF. However, because this was an open-label study, the results must be interpreted with caution, and further double-blind, placebo-controlled, dose ranging trials supplemented with different antioxidants together with intranasal steroids are suggested. PMID- 27658185 TI - Immunoglobulin G4-related sclerosing disease of the paranasal sinuses: A case report and literature review. AB - OBJECTIVE: Immunoglobulin G4 (IgG4) related sclerosing disease (RSD) of the paranasal sinuses is a rare lesion of dense lymphoplasmacytic tissue, with a high proportion of IgG4+ plasma cells. We presented a rare case of IgG4-RSD with isolated involvement of the paranasal sinuses in the absence of multiorgan involvement. METHODS: A case report and comprehensive literature review. RESULTS: To our knowledge, only 11 cases of IgG4-RSD with paranasal sinus involvement have been reported. Patients with IgG4-RSD commonly present with epistaxis and symptoms that mimic chronic rhinosinusitis, e.g., rhinorrhea, nasal obstruction, and facial pressure. On imaging, an expansive and erosive process is described. Surgery provides tissue for immunohistologic evaluation; however, there is a paucity of evidence about the direct extent of surgical resection or medical therapies. Postoperative steroids were typically started, although the regimen was not standardized. CONCLUSION: Few cases of paranasal sinus IgG4-RSD have been reported in the literature. Evidence-based recommendations regarding treatment and surveillance of paranasal sinus IgG4-RSD are lacking; however, most reports describe systemic steroids as the mainstay of treatment. This single subject analysis, with a review of previously reported cases adds to the expanding body of data related to this rare disorder. PMID- 27658186 TI - A novel insight into the immunologic basis of chronic granulomatous invasive fungal rhinosinusitis. AB - BACKGROUND: Chronic granulomatous invasive fungal rhinosinusitis (CGIFRS) is a rare disease. The underlying immune responses that drive the development of CGIFRS, as opposed to successful pathogen clearance and controlled inflammation, are not currently known. OBJECTIVE: To characterize the immune responses associated with CGIFRS. METHODS: In addition to a battery of basic investigations, more in-depth immunologic testing involves ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with interleukin (IL) 12, was undertaken to investigate cell-mediated immune responses associated with CGIFRS. RESULTS: Ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with IL 12 identified reduced interferon gamma and increased IL-17A levels within the supernatant, which indicated increased in vivo T-helper (Th)17 responses and impaired Th1 responses compared with healthy controls. CONCLUSION: These findings suggest that the development of CGIFRS may be associated with an abnormally exaggerated host Th17 response, which caused failure to clear the fungal pathogen with refractory fungal infection of mucosal membranes, resulting in chronic tissue inflammation. PMID- 27658187 TI - c-Met inhibition enhances chemosensitivity of human ovarian cancer cells. AB - In clinical practice, human ovarian cancer shows considerable resistance to chemotherapy. This study aimed to investigate the role of c-Met in the chemoresistance of ovarian cancer. Ovarian cancer cell line SKOV3 and OVCAR-3 were pretreated with c-Met inhibitor INCB28060, and then treated with paclitaxel. Cell survival, cell cycle and apoptosis were analyzed by MTT assay, flow cytometry analysis and TUNEL assay, respectively. The activation of c-Met signalling was detected by western blot analysis. INCB28060 inhibited the survival of SKOV3 and OVCAR-3 cells and enhanced the chemosensitivity of SKOV3 and OVCAR-3 cells to paclitaxel. INCB28060 inhibited c-Met signalling, caused mitochondrial membrane depolarization and DNA repair, and induced the apoptosis of SKOV3 and OVCAR-3 cells. c-Met plays an important role in mediating the chemoresistance of ovarian cancer. The combination of c-Met inhibitor and chemotherapy is a promising strategy to human ovarian cancer. PMID- 27658188 TI - The International Haemovigilance Network Database for the Surveillance of Adverse Reactions and Events in Donors and Recipients of Blood Components: technical issues and results. AB - BACKGROUND AND OBJECTIVES: The International Haemovigilance Network's ISTARE is an online database for surveillance of all adverse reactions (ARs) and adverse events (AEs) associated with donation of blood and transfusion of blood components, irrespective of severity or the harm caused. ISTARE aims to unify the collection and sharing of information with a view to harmonizing best practices for haemovigilance systems around the world. MATERIALS AND METHODS: Adverse reactionss and adverse events are recorded by blood component, type of reaction, severity and imputability to transfusion, using internationally agreed standard definitions. RESULTS: From 2006 to 2012, 125 national sets of annual aggregated data were received from 25 countries, covering 132.8 million blood components issued. The incidence of all ARs was 77.5 per 100 000 components issued, of which 25% were severe (19.1 per 100 000). Of 349 deaths (0.26 per 100 000), 58% were due to the three ARs related to the respiratory system: transfusion-associated circulatory overload (TACO, 27%), transfusion-associated acute lung injury (TRALI, 19%) and transfusion-associated dyspnoea (TAD, 12%). Cumulatively, 594 477 donor complications were reported (rate 660 per 100 000), of which 2.9% were severe. CONCLUSIONS: ISTARE is a well-established surveillance tool offering important contributions to international efforts to maximize transfusion safety. PMID- 27658189 TI - Spelling across Tasks and Levels of Language in a Transparent Orthography. AB - The paper reports the results of two studies on the spelling performance of 1st graders in a transparent writing system. The spelling performance of Italian children was assessed to determine the cross-task relationship between spelling to dictation and spontaneous spelling at the single word level (Study 1) and at the text level (Study 2), respectively. In study 1, 132 Italian children's spelling performance was assessed in 1st grade through two standardized tasks, i.e., word dictation, and spontaneous word spelling. In study 2, spelling performance of 81 Italian children was assessed in 1st grade through two tasks, i.e., text dictation, and spontaneous text spelling. In Study 1, spelling words and pseudo-words to dictation was found to be more difficult than spontaneous spelling of words. This effect was verified for all children (including low achievers and spelling impaired). The moderate correlation found between spelling to dictation and spontaneous spelling indicated that the two tasks are supported by partially different spelling processes and confirmed suggestions for including both types of spelling assessments in the school. In Study 2, children's spelling performances were not dependent across the two tasks (i.e., spelling a text under dictation or spontaneously). The two tasks shared the level of difficulty but performance in one task was not predictive of performance in the second task. Strong individual differences between children were found at the text level as a function of task. Similar to Study 1, the moderate correlation between spelling text to dictation and spontaneous spelling confirmed the usefulness of adopting both spelling assessments at school. PMID- 27658190 TI - Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes. AB - OBJECTIVE: Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes. STUDY DESIGN: Preterm infants <= 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord). RESULTS: Of the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnionitis but no funisitis (AC), and 26 infants had chorioamnionitis with funisitis (ACF). The fecal samples from ACF infants collected by day of life 7 had higher relative abundance of family Mycoplasmataceae (phylum Tenericutes), genus Prevotella (phylum Bacteroidetes) and genus Sneathia (phylum Fusobacteria). Further, AC and ACF infants had higher incidence of late-onset sepsis/death as a combined outcome. Presence of specific clades in fecal samples, specifically, order Fusobacteria, genus Sneathia or family Mycoplasmataceae, were significantly associated with higher risk of sepsis or death. CONCLUSION: The results support the hypothesis that specific alterations in the pioneering infant gastrointestinal microbiota induced by chorioamnionitis predispose to neonatal sepsis or death. PMID- 27658191 TI - No Evidence for a Saccadic Range Effect for Visually Guided and Memory-Guided Saccades in Simple Saccade-Targeting Tasks. AB - Saccades to single targets in peripheral vision are typically characterized by an undershoot bias. Putting this bias to a test, Kapoula [1] used a paradigm in which observers were presented with two different sets of target eccentricities that partially overlapped each other. Her data were suggestive of a saccadic range effect (SRE): There was a tendency for saccades to overshoot close targets and undershoot far targets in a block, suggesting that there was a response bias towards the center of eccentricities in a given block. Our Experiment 1 was a close replication of the original study by Kapoula [1]. In addition, we tested whether the SRE is sensitive to top-down requirements associated with the task, and we also varied the target presentation duration. In Experiments 1 and 2, we expected to replicate the SRE for a visual discrimination task. The simple visual saccade-targeting task in Experiment 3, entailing minimal top-down influence, was expected to elicit a weaker SRE. Voluntary saccades to remembered target locations in Experiment 3 were expected to elicit the strongest SRE. Contrary to these predictions, we did not observe a SRE in any of the tasks. Our findings complement the results reported by Gillen et al. [2] who failed to find the effect in a saccade-targeting task with a very brief target presentation. Together, these results suggest that unlike arm movements, saccadic eye movements are not biased towards making saccades of a constant, optimal amplitude for the task. PMID- 27658192 TI - Emotion regulation strategies in individuals with cocaine use disorder maintained on methadone. AB - BACKGROUND AND OBJECTIVES: Cognitive reappraisal (CR) and emotional suppression (ES), two emotion regulation strategies, are disrupted in other substance use disorders but have not been studied in cocaine dependence. METHODS: Methadone maintained individuals with cocaine dependence (N = 72) completed assessment of CR, ES, cocaine use, and psychiatric symptoms. RESULTS: CR scores were associated with lower depression scores (r = -.29, p = .01), but not with cocaine abstinence during 8 weeks of treatment (r = .12, p = .29). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: CR appeared relevant to cocaine-dependent individuals' depression, but was not associated with abstinence or treatment outcome. (Am J Addict 2016;25:529-532). PMID- 27658193 TI - Sensitive Detection and Simultaneous Discrimination of Influenza A and B Viruses in Nasopharyngeal Swabs in a Single Assay Using Next-Generation Sequencing-Based Diagnostics. AB - Reassortment of 2009 (H1N1) pandemic influenza virus (pdH1N1) with other strains may produce more virulent and pathogenic forms, detection and their rapid characterization is critical. In this study, we reported a "one-size-fits-all" approach using a next-generation sequencing (NGS) detection platform to extensively identify influenza viral genomes for diagnosis and determination of novel virulence and drug resistance markers. A de novo module and other bioinformatics tools were used to generate contiguous sequence and identify influenza types/subtypes. Of 162 archived influenza-positive patient specimens, 161(99.4%) were positive for either influenza A or B viruses determined using the NGS assay. Among these, 135(83.3%) were A(H3N2), 14(8.6%) were A(pdH1N1), 2(1.2%) were A(H3N2) and A(pdH1N1) virus co-infections and 10(6.2%) were influenza B viruses. Of the influenza A viruses, 66.7% of A(H3N2) viruses tested had a E627K mutation in the PB2 protein, and 87.8% of the influenza A viruses contained the S31N mutation in the M2 protein. Further studies demonstrated that the NGS assay could achieve a high level of sensitivity and reveal adequate genetic information for final laboratory confirmation. The current diagnostic platform allows for simultaneous identification of a broad range of influenza viruses, monitoring emerging influenza strains with pandemic potential that facilitating diagnostics and antiviral treatment in the clinical setting and protection of the public health. PMID- 27658194 TI - Distance-Based and Low Energy Adaptive Clustering Protocol for Wireless Sensor Networks. AB - A wireless sensor network (WSN) comprises small sensor nodes with limited energy capabilities. The power constraints of WSNs necessitate efficient energy utilization to extend the overall network lifetime of these networks. We propose a distance-based and low-energy adaptive clustering (DISCPLN) protocol to streamline the green issue of efficient energy utilization in WSNs. We also enhance our proposed protocol into the multi-hop-DISCPLN protocol to increase the lifetime of the network in terms of high throughput with minimum delay time and packet loss. We also propose the mobile-DISCPLN protocol to maintain the stability of the network. The modelling and comparison of these protocols with their corresponding benchmarks exhibit promising results. PMID- 27658196 TI - Treatment of sporadic port-wine stains: a retrospective review of 17 cases consecutively treated by pulsed sequential dual wavelength 595 and 1064 nm laser. AB - BACKGROUND: Port-wine stains (PWS) are relatively common and often cause cosmetic and psychological concerns. The pulsed dye laser is currently the treatment of choice for PWS. OBJECTIVE: To assess the effectiveness of the pulsed sequential dual wavelength 595 and 1064 nm laser as first-line treatment for PWS and to identify prognostic factors for treatment outcome in a retrospective series of 17 consecutive previously untreated patients. METHODS: The response to treatment was evaluated 2 months after treatment utilizing comparative photographs and a standard physician global assessment (PGA) grading system. Furthermore, measurement of the normalized erythema index (NEI) reduction (DeltaNEI%) was carried out using an image analysis system. The subjective improvement was assessed using a patient's satisfaction questionnaire. Multiple linear regression models were finally used to identify factors associated with DeltaNEI% and patients' satisfaction. RESULTS: Seventeen patients, with PWS, including 12 children were included. The average PGA assessment was 2.5 +/- 1.3 corresponding to an amelioration of 50% with a high intraclass correlation coefficient among the experts. The before-after NEI showed a statistically significant mean reduction of 3.5 +/- 2.6 units, corresponding to a relative reduction of 31%. Questionnaires showed that the satisfaction was very good with an average score of 6.1 points on a scale ranging from -10 to 10 points. Multiple regression analysis revealed that location in the frontotemporal area was associated with a significant reduction in DeltaNEI% (38.4%; 95% CI 4.3, 72.6). Presence of PWS on the neck was associated with a lower patient satisfaction (-3.7 points; 95% CI 6.5, -0.9). There were no significant side-effects, except for transient discomfort and purpura. CONCLUSIONS: Based on the results obtained in the largest reported series so far, the pulsed sequential dual wavelength 595 and 1064 nm laser represents an effective and safe first-line therapeutic option for the treatment of PWS. PMID- 27658197 TI - Coronary Computed Tomographic Angiography at 80 kVp and Knowledge-Based Iterative Model Reconstruction Is Non-Inferior to that at 100 kVp with Iterative Reconstruction. AB - The aims of this study were to compare the image noise and quality of coronary computed tomographic angiography (CCTA) at 80 kVp with knowledge-based iterative model reconstruction (IMR) to those of CCTA at 100 kVp with hybrid iterative reconstruction (IR), and to evaluate the feasibility of a low-dose radiation protocol with IMR. Thirty subjects who underwent prospective electrocardiogram gating CCTA at 80 kVp, 150 mAs, and IMR (Group A), and 30 subjects with 100 kVp, 150 mAs, and hybrid IR (Group B) were retrospectively enrolled after sample-size calculation. A BMI of less than 25 kg/m2 was required for inclusion. The attenuation value and image noise of CCTA were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated at the proximal right coronary artery and left main coronary artery. The image noise was analyzed using a non-inferiority test. The CCTA images were qualitatively evaluated using a four-point scale. The radiation dose was significantly lower in Group A than Group B (0.69 +/- 0.08 mSv vs. 1.39 +/- 0.15 mSv, p < 0.001). The attenuation values were higher in Group A than Group B (p < 0.001). The SNR and CNR in Group A were higher than those of Group B. The image noise of Group A was non-inferior to that of Group B. Qualitative image quality of Group A was better than that of Group B (3.6 vs. 3.4, p = 0.017). CCTA at 80 kVp with IMR could reduce the radiation dose by about 50%, with non-inferior image noise and image quality than those of CCTA at 100 kVp with hybrid IR. PMID- 27658195 TI - Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL 17A. AB - Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5-10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-gamma. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-gamma. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients. PMID- 27658198 TI - Expanding Praziquantel (PZQ) Access beyond Mass Drug Administration Programs: Paving a Way Forward for a Pediatric PZQ Formulation for Schistosomiasis. PMID- 27658199 TI - Dietary Flavones as Dual Inhibitors of DNA Methyltransferases and Histone Methyltransferases. AB - Methylation of DNA and histone proteins are mutually involved in the epigenetic regulation of gene expression mediated by DNA methyltransferases (DNMTs) and histone methyltransferases (HMTs). DNMTs methylate cytosine residues within gene promoters, whereas HMTs catalyze the transfer of methyl groups to lysine and arginine residues of histone proteins, thus causing chromatin condensation and transcriptional repression, which play an important role in the pathogenesis of cancer. The potential reversibility of epigenetic alterations has encouraged the development of dual pharmacologic inhibitors of DNA and histone methylation as anticancer therapeutics. Dietary flavones can affect epigenetic modifications that accumulate over time and have shown anticancer properties, which are undefined. Through DNA binding and in silico protein-ligand docking studies with plant flavones viz. Apigenin, Chrysin and Luteolin, the effect of flavones on DNA and histone methylation was assessed. Spectroscopic analysis of flavones with calf-thymus DNA revealed intercalation as the dominant binding mode, with specific binding to a GC-rich sequence in the DNA duplex. A virtual screening approach using a model of the catalytic site of DNMT and EZH2 demonstrated that plant flavones are tethered at both ends inside the catalytic pocket of DNMT and EZH2 by means of hydrogen bonding. Epigenetic studies performed with flavones exhibited a decrease in DNMT enzyme activity and a reversal of the hypermethylation of cytosine bases in the DNA and prevented cytosine methylation in the GC-rich promoter sequence incubated with the M.SssI enzyme. Furthermore, a marked decrease in HMT activity and a decrease in EZH2 protein expression and trimethylation of H3K27 were noted in histones isolated from cancer cells treated with plant flavones. Our results suggest that dietary flavones can alter DNMT and HMT activities and the methylation of DNA and histone proteins that regulate epigenetic modifications, thus providing a significant anticancer effect by altering epigenetic processes involved in the development of cancer. PMID- 27658200 TI - Liver transplantation after share 35: Impact on pretransplant and posttransplant costs and mortality. AB - Share 35 was implemented in 2013 to direct livers to the most urgent candidates by prioritizing Model for End-Stage Liver Disease (MELD) >= 35 patients. We aim to evaluate this policy's impact on costs and mortality. Our study includes 834 wait-listed patients and 338 patients who received deceased donor, solitary liver transplants at Mayo Clinic between January 2010 and December 2014. Of these patients, 101 (30%) underwent transplantation after Share 35. After Share 35, 29 (28.7%) MELD >= 35 patients received transplants, as opposed to 46 (19.4%) in the pre-Share 35 era (P = 0.06). No significant difference in 90-day wait-list mortality (P = 0.29) nor 365-day posttransplant mortality (P = 0.68) was found between patients transplanted before or after Share 35. Mean costs were $3,049 (P = 0.30), $5226 (P = 0.18), and $10,826 (P = 0.03) lower post-Share 35 for the 30 , 90-, and 365-day pretransplant periods, and mean costs were $5010 (P = 0.41) and $5859 (P = 0.57) higher, and $9145 (P = 0.54) lower post-Share 35 for the 30 , 90-, and 365-day posttransplant periods. In conclusion, the added cost of transplanting more MELD >= 35 patients may be offset by pretransplant care cost reduction. Despite shifting organs to critically ill patients, Share 35 has not impacted mortality significantly. Liver Transplantation 23:11-18 2017 AASLD. PMID- 27658201 TI - Molecular Evolution of MDM1, a "Duplication-Resistant" Gene in Vertebrates. AB - BACKGROUND: The mouse double minute 1 (Mdm1) gene was first reported and cloned in mouse tumor cell lines as an oncogene candidate. Later, it was found that mutation of Mdm1 might cause age-related retinal degeneration 2 in mice by genetic linkage analysis. Additionally, the MDM1 protein was found to be expressed in the centrosomes, cilia, and the nucleus of multiciliated tracheal epithelial cells in mice. These observations suggest that MDM1 may have some basal functions in cell physiology. However, the evolutionary history of this gene and its expression during embryonic development remain largely unexplored. RESULTS: Using molecular phylogenetic analysis, we found that the MDM1 gene encoded an evolutionarily conserved protein across all metazoans. We also found that the MDM1 gene was in a conserved synteny in vertebrates. In almost all the species that were analyzed, there was only one MDM1 gene based on current genome annotations. Since vertebrate genomes underwent two to three rounds of whole genome duplications around the origin of the vertebrates, it is interesting that only one MDM1 ohnolog was retained. This observation implies that other MDM1 ohnologs were lost after the whole-genome duplications. Furthermore, using whole mount in situ hybridization, we found that mdm1 was expressed in the forebrain, nephric ducts, and tail buds during zebrafish early embryonic development. CONCLUSION: MDM1 is an evolutionary conserved gene, and its homologous genes can be traced back to basal metazoan lineages. In vertebrates, the MDM1 gene is in a conserved synteny and there is only one MDM1 ohnolog suggesting it is a "duplication-resistant" gene. Its expression patterns in early zebrafish embryos indicate that mdm1 may play important roles in the development of the central nervous system, kidneys, and hematopoietic system. PMID- 27658202 TI - Grb7 Protein Stability Modulated by Pin1 in Association with Cell Cycle Progression. AB - Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. The molecular mechanisms underlying the regulation of Grb7 remain unclear. Here, we revealed a novel negative post-translational regulation of Grb7 by the peptidyl-prolyl cis/trans isomerase, Pin1. Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. Indeed, we found that Pin1 exerts its peptidyl-prolyl cis/trans isomerase activity in the modulation of Grb7 protein stability in regulation of cell cycle progression at the G2-M phase. This study illustrates a novel regulatory mechanism in modulating Grb7-mediated signaling, which may take part in pathophysiological consequences. PMID- 27658203 TI - Effects of Grazing Management and Cattle on Aquatic Habitat Use by the Anuran Pseudopaludicola mystacalis in Agro-Savannah Landscapes. AB - Because of their strong dependence on the environment, the spatial distribution of pond-breeding amphibians can be greatly influenced by anthropogenic habitat alteration. In some agricultural landscapes in Brazil, the anuran Pseudopaludicola mystacalis appears to be highly influenced by land use. Because adult males and tadpoles of this species are usually found in marshy areas with cattle hoof prints, we hypothesized that P. mystacalis preferentially occupies aquatic habitats with marshy areas that are trampled by cattle. To test our hypothesis, we assessed whether the occurrence of P. mystacalis is associated with the presence of cattle and trampled marshy areas, and which environmental features best explain the spatial distribution and abundance of P. mystacalis. To do so, we sampled 38 aquatic habitats in an area intensely used for livestock in southeastern Brazil. We found that the presence of cattle and trampled marshy areas in aquatic habitats are positively associated to P. mystacalis occurrence. Additionally, the abundance of calling males is better predicted by variables of landscape and local habitat structure. Specifically, the size of trampled marshy areas and the proportion of herbaceous vegetation within the aquatic habitat are positively associated with abundance, while distance to nearest aquatic habitat are negatively associated with abundance of calling males. All three of these variables can be directly or indirectly linked to the presence of cattle or grazing management. Therefore, this work shows evidence that Pseudopaludicola mystacalis is positively influenced by grazing management with cattle, and draws attention to other unknown potential consequences of different land use to fresh water diversity. PMID- 27658204 TI - Early Duplication of a Single MHC IIB Locus Prior to the Passerine Radiations. AB - A key characteristic of MHC genes is the persistence of allelic lineages over macroevolutionary periods, often through multiple speciation events. This phenomenon, known as trans-species polymorphism (TSP), is well documented in several major taxonomic groups, but has less frequently been observed in birds. The order Passeriformes is arguably the most successful terrestrial vertebrate order in terms of diversity of species and ecological range, but the reasons for this success remain unclear. Passerines exhibit the most highly duplicated MHC genes of any major vertebrate taxonomic group, which may generate increased immune response relative to other avian orders with fewer MHC loci. Here, we describe phylogenetic patterns of the MHC IIB in the passerine family Corvidae. Our results indicate wide-spread TSP within this family, with at least four supported MHC IIB allelic lineages that predate speciation by many millions of years. Markov chain Monte Carlo simulations indicate that divergence of these lineages occurred near the time of the divergence of the Passeriformes and other avian orders. We suggest that the current MHC diversity observed in passerines is due in part to the multiple duplication of a single MHC locus, DAB1, early in passerine evolution and that subsequent duplications of these paralogues have contributed to the enormous success of this order by increasing their ability to recognize and mount immune responses to novel pathogens. PMID- 27658205 TI - Total Bee Dependence on One Flower Species Despite Available Congeners of Similar Floral Shape. AB - Extreme specialization is a common phenomenon in antagonistic biotic interactions but it is quite rare in mutualistic ones. Indeed, bee specialization on a single flower species (monolecty) is a questioned fact. Here, we provide multiple lines of evidence on true monolecty in a solitary bee (Flavipanurgus venustus, Andrenidae), which is consistent across space (18 sites in SW Iberian Peninsula) and time (three years) despite the presence of closely related congeneric plant species whose flowers are morphologically similar. The host flower (Cistus crispus, Cistaceae) is in turn a supergeneralist, visited by at least 85 insect species. We uncover ultraviolet light reflectance as a distinctive visual cue of the host flower, which can be a key mechanism because bee specialization has an innate basis to recognize specific signals. Moreover, we hypothesized that a total dependence on an ephemeral resource (i.e. one flower species) must lead to spatiotemporal matching with it. Accordingly, we prove that the bee's flight phenology is synchronized with the blooming period of the host flower, and that the densities of bee populations mirror the local densities of the host flower. This case supports the 'predictable plethora' hypothesis, that is, that host specialization in bees is fostered by plant species providing predictably abundant floral resources. Our findings, along with available phylogenetic information on the genus Cistus, suggest the importance of historical processes and cognitive constraints as drivers of specialization in bee-plant interactions. PMID- 27658207 TI - Correction: Bilateral tDCS on Primary Motor Cortex: Effects on Fast Arm Reaching Tasks. AB - [This corrects the article DOI: 10.1371/journal.pone.0160063.]. PMID- 27658206 TI - Polyglutamine Tract Expansion Increases S-Nitrosylation of Huntingtin and Ataxin 1. AB - Expansion of the polyglutamine (polyQ) tract in the huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited movement disorder linked to neurodegeneration in the striatum and cortex. S-nitrosylation and S-acylation of cysteine residues regulate many functions of cytosolic proteins. We therefore used a resin-assisted capture approach to identify these modifications in Htt. In contrast to many proteins that have only a single S-nitrosylation or S-acylation site, we identified sites along much of the length of Htt. Moreover, analysis of cells expressing full-length Htt or a large N-terminal fragment of Htt shows that polyQ expansion strongly increases Htt S-nitrosylation. This effect appears to be general since it is also observed in Ataxin-1, which causes spinocerebellar ataxia type 1 (SCA1) when its polyQ tract is expanded. Overexpression of nitric oxide synthase increases the S-nitrosylation of normal Htt and the frequency of conspicuous juxtanuclear inclusions of Htt N-terminal fragments in transfected cells. Taken together with the evidence that S-nitrosylation of Htt is widespread and parallels polyQ expansion, these subcellular changes show that S nitrosylation affects the biology of this protein in vivo. PMID- 27658208 TI - A Novel Inflammation- and Nutrition-Based Prognostic System for Patients with Laryngeal Squamous Cell Carcinoma: Combination of Red Blood Cell Distribution Width and Body Mass Index (COR-BMI). AB - BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a head and neck cancer type. In this study, we introduced a novel inflammation- and nutrition-based prognostic system, referred to as COR-BMI (Combination of red blood cell distribution width and body mass index), for LSCC patients. METHODS: A total of 807 LSCC patients (784 male and 23 female, 22-87 y of age) who underwent surgery were enrolled in this retrospective cohort study. The patients were stratified by COR-BMI into three groups: COR-BMI (0) (RDW <= 13.1 and BMI >= 25); COR-BMI (1) (RDW <= 13.1 and BMI < 18.5 or 18.5 <= BMI < 25; RDW > 13.1 and 18.5 <= BMI < 25 or BMI >= 25); or COR-BMI (2) (RDW > 13.1 and BMI < 18.5). Cox regression models were used to investigate the association between COR-BMI and cancer-specific survival (CSS) rate among LSCC patients. RESULTS: The 5-y, 10-y, and 15-y CSS rates were 71.6%, 60.1%, and 55.4%, respectively. There were significant differences among the COR-BMI groups in age (< 60 versus >= 60 y; P = 0.005) and T stage (T1, T2, T3, or T4; P = 0.013). Based on the results, COR-BMI (1 versus 0: HR = 1.76; 95% CI = 0.98-3.15; 2 versus 0: HR = 2.91; 95% CI = 1.53-5.54, P = 0.001) was a significant independent predictor of CSS. CONCLUSION: COR-BMI is a novel inflammation- and nutrition-based prognostic system, which could predict long-term survival in LSCC patients who underwent surgery. PMID- 27658210 TI - Vesicle Size Distribution as a Novel Nuclear Forensics Tool. AB - The first nuclear bomb detonation on Earth involved a plutonium implosion-type device exploded at the Trinity test site (33 degrees 40'38.28"N, 106 degrees 28'31.44"W), White Sands Proving Grounds, near Alamogordo, New Mexico. Melting and subsequent quenching of the local arkosic sand produced glassy material, designated "Trinitite". In cross section, Trinitite comprises a thin (1-2 mm), primarily glassy surface above a lower zone (1-2 cm) of mixed melt and mineral fragments from the precursor sand. Multiple hypotheses have been put forward to explain these well-documented but heterogeneous textures. This study reports the first quantitative textural analysis of vesicles in Trinitite to constrain their physical and thermal history. Vesicle morphology and size distributions confirm the upper, glassy surface records a distinct processing history from the lower region, that is useful in determining the original sample surface orientation. Specifically, the glassy layer has lower vesicle density, with larger sizes and more rounded population in cross-section. This vertical stratigraphy is attributed to a two-stage evolution of Trinitite glass from quench cooling of the upper layer followed by prolonged heating of the subsurface. Defining the physical regime of post-melting processes constrains the potential for surface mixing and vesicle formation in a post-detonation environment. PMID- 27658211 TI - Correction: Energy Expenditure and Substrate Oxidation in Response to Side Alternating Whole Body Vibration across Three Commonly-Used Vibration Frequencies. AB - [This corrects the article DOI: 10.1371/journal.pone.0151552.]. PMID- 27658209 TI - Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study. AB - BACKGROUND: Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose dependent. METHODS AND FINDINGS: This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged >=40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA1c between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16% (95% confidence interval [CI]: 0.05-0.27%) in all COPD patients, and 0.25% (95% CI: 0.10-0.40%) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (>250 mg) had greater odds of increased HbA1c and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses (<=125 mg). CONCLUSION: For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression. TRIAL REGISTRATION: ENCePP ENCEPP/SDPP/6804. PMID- 27658212 TI - One-year follow-up study of first suicide attempts in first episode psychosis: Personality traits and temporal pattern. AB - OBJECTIVES: The highest suicide rates occur after psychiatric hospitalization or soon after discharge. In addition to other factors, personality traits have been suggested as predictors of suicide attempts (SA) after first episode psychosis (FEP). In this study we examined their temporal pattern and the influence of personality traits on first suicide attempts (fSA) during one year after FEP. METHOD: One-year follow-up of 65 FEP patients. Bivariate and multivariable analyses were performed to explore the relationship between personality traits and fSA. This analysis was also adjusted for a set of sociodemographic, clinical and psychopathological variables. RESULTS: fSAs in the six months following FEP were predicted by higher scores in passive-dependent personality traits (OR = 2.42, 95% CI = 1.15-5.09) and severity of symptoms at onset (OR = 2.00, 95% CI = 1.07-3.76). Severity of symptoms at onset (OR = 2.71, CI = 1.15-6.39) was the most significant predictor of fSA from six to twelve months after FEP. Seventy percent of fSA occurred during the first six months after FEP, decreasing considerably afterwards. CONCLUSIONS: Our study suggests that personality traits play a role in fSA after FEP. Specifically, passive-dependent personality traits emerged as a predictor of fSA in the six months following FEP. Severity of symptoms at onset predicted early and late first suicide attempts. We also found that risk of fSA is highest during the six months following FEP. These results can contribute to the implementation of prevention program. PMID- 27658213 TI - The aging brain: Movement speed and spatial control. AB - BACKGROUND/OBJECTIVES: With aging, people commonly develop motor slowing (bradykinesia). Although this slowness with aging may be entirely related to degradation of the cerebral networks important in motor programing, it is possible that, at least in part, it may be a learned procedure for enhancing the accuracy and/or precision of movements. The goal of this study is to test these contradictory hypotheses. METHODS: Twenty-four healthy adults, 12 younger than age 26 and 12 older than age 65 were asked to make alternative marks with a pen between a card centered in front of them and a series of circles distributed across a page. Performance was timed, and participants were instructed to complete the task as quickly as possible while not sacrificing accuracy for speed. The circle sizes and hand used varied by trial. RESULTS: The older adults performed the task more slowly for all target circle diameters. As the circles decreased in size, the younger adults performed the task more rapidly than did the older participants, but the younger participants also had a greater decline in accuracy. CONCLUSIONS: During this aiming task, healthy older adults were less likely than younger adults to sacrifice accuracy for speed. Thus, at least in part, their slowing may be a learned adaptive strategy. PMID- 27658214 TI - Separating Predicted and Perceived Sensory Consequences of Motor Learning. AB - During motor adaptation the discrepancy between predicted and actually perceived sensory feedback is thought to be minimized, but it can be difficult to measure predictions of the sensory consequences of actions. Studies attempting to do so have found that self-directed, unseen hand position is mislocalized in the direction of altered visual feedback. However, our lab has shown that motor adaptation also leads to changes in perceptual estimates of hand position, even when the target hand is passively displaced. We attribute these changes to a recalibration of hand proprioception, since in the absence of a volitional movement, efferent or predictive signals are likely not involved. The goal here is to quantify the extent to which changes in hand localization reflect a change in the predicted sensory (visual) consequences or a change in the perceived (proprioceptive) consequences. We did this by comparing changes in localization produced when the hand movement was self-generated ('active localization') versus robot-generated ('passive localization') to the same locations following visuomotor adaptation to a rotated cursor. In this passive version, there should be no predicted consequences of these robot-generated hand movements. We found that although changes in localization were somewhat larger in active localization, the passive localization task also elicited substantial changes. Our results suggest that the change in hand localization following visuomotor adaptation may not be based entirely on updating predicted sensory consequences, but may largely reflect changes in our proprioceptive state estimate. PMID- 27658215 TI - Effectiveness of Onsite Nurse Mentoring in Improving Quality of Institutional Births in the Primary Health Centres of High Priority Districts of Karnataka, South India: A Cluster Randomized Trial. AB - BACKGROUND: In India, although the proportion of institutional births is increasing, there are concerns regarding quality of care. We assessed the effectiveness of a nurse-led onsite mentoring program in improving quality of care of institutional births in 24/7 primary health centres (PHCs that are open 24 hours a day, 7 days a week) of two high priority districts in Karnataka state, South India. Primary outcomes were improved facility readiness and provider preparedness in managing institutional births and associated complications during child birth. METHODS: All functional 24/7 PHCs in the two districts were included in the study. We used a parallel, cluster randomized trial design in which 54 of 108 facilities received six onsite mentoring visits, along with an initial training update and specially designed case sheets for providers; the control arm received just the initial training update and the case sheets. Pre- and post intervention surveys were administered in April-2012 and August-2013 using facility audits, provider interviews and case sheet audits. The provider interviews were administered to all staff nurses available at the PHCs and audits were done of all the filled case sheets during the month prior to data collection. In addition, a cost analysis of the intervention was undertaken. RESULTS: Between the surveys, we achieved coverage of 100% of facilities and 91.2% of staff nurse interviews. Since the case sheets were newly designed, case sheet audit data were available only from the end line survey for about 80.2% of all women in the intervention facilities and 57.3% in the control facilities. A higher number of facilities in the intervention arm had all appropriate drugs, equipment and supplies to deal with gestational hypertension (19 vs.3, OR (odds ratio) 9.2, 95% C.I 2.5 to33.6), postpartum haemorrhage (29 vs. 12, OR 3.7, 95% C.I 1.6 to8.3); and obstructed labour (25 vs.9, OR 3.4, 95% CI 1.6 to8.3). The providers in the intervention arm had better knowledge of active management of the third stage of labour (82.4% vs.35.8%, AOR (adjusted odds ratio) 10, 95% C.I 5.5 to 18.2); management of maternal sepsis (73.5% vs. 10.9%, AOR 36.1, 95% C.I 13.6 to 95.9); neonatal resuscitation (48.5% vs.11.7%, AOR 10.7, 95% C.I 4.6 to 25.0) and low birth weight newborn care (58.1% vs. 40.9%, AOR 2.4, 95% C.I 1.2 to 4.7). The case sheet audits revealed that providers in the intervention arm showed greater compliance with the protocols during labour monitoring (77.3% vs. 32.1%, AOR 25.8, 95% C.I 9.6 to 69.4); delivery and immediate post-partum care for mothers (78.6% vs. 31.8%, AOR 22.1, 95% C.I 8.0 to 61.4) and for newborns (73.9% vs. 32.8%, AOR 24.1, 95% C.I 8.1 to 72.0). The cost analysis showed that the intervention cost an additional $5.60 overall per delivery. CONCLUSIONS: The mentoring program successfully improved provider preparedness and facility readiness to deal with institutional births and associated complications. It is feasible to improve the quality of institutional births at a large operational scale, without substantial incremental costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02004912. PMID- 27658216 TI - Effects of Mental Load and Fatigue on Steady-State Evoked Potential Based Brain Computer Interface Tasks: A Comparison of Periodic Flickering and Motion-Reversal Based Visual Attention. AB - Steady-state visual evoked potentials (SSVEP) based paradigm is a conventional BCI method with the advantages of high information transfer rate, high tolerance to artifacts and the robust performance across users. But the occurrence of mental load and fatigue when users stare at flickering stimuli is a critical problem in implementation of SSVEP-based BCIs. Based on electroencephalography (EEG) power indices alpha, theta, theta + alpha, ratio index theta/alpha and response properties of amplitude and SNR, this study quantitatively evaluated the mental load and fatigue in both of conventional flickering and the novel motion reversal visual attention tasks. Results over nine subjects revealed significant mental load alleviation in motion-reversal task rather than flickering task. The interaction between factors of "stimulation type" and "fatigue level" also illustrated the motion-reversal stimulation as a superior anti-fatigue solution for long-term BCI operation. Taken together, our work provided an objective method favorable for the design of more practically applicable steady-state evoked potential based BCIs. PMID- 27658217 TI - Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies. AB - Sexual dimorphism results from sex-biased gene expression, which evolves when selection acts differently on males and females. While there is an intimate connection between sex-biased gene expression and sex-specific selection, few empirical studies have studied this relationship directly. Here we compare the two on a genome-wide scale in humans and flies. We find a distinctive "Twin Peaks" pattern in humans that relates the strength of sex-specific selection, quantified by genetic divergence between male and female adults at autosomal loci, to the degree of sex-biased expression. Genes with intermediate degrees of sex-biased expression show evidence of ongoing sex-specific selection, while genes with either little or completely sex-biased expression do not. This pattern apparently results from differential viability selection in males and females acting in the current generation. The Twin Peaks pattern is also found in Drosophila using a different measure of sex-specific selection acting on fertility. We develop a simple model that successfully recapitulates the Twin Peaks. Our results suggest that many genes with intermediate sex-biased expression experience ongoing sex-specific selection in humans and flies. PMID- 27658219 TI - [Molekulargenetische Diagnostik - Was wissen die Maschinen? Was wollen wir wissen?] PMID- 27658218 TI - Cognitive-behavior therapy singly and combined with medication for persistent insomnia: Impact on psychological and daytime functioning. AB - : While impairment of daytime functioning due to poor sleep is often the main determinant for seeking treatment, few studies have examined the clinical impact of insomnia therapies on daytime outcomes. The main objective of this study was to evaluate the impact of cognitive-behavior therapy (CBT), alone and combined with medication, on various indices of daytime and psychological functioning. Participants were 160 individuals with chronic insomnia who received CBT alone or CBT plus medication (zolpidem) for an initial six-week therapy, followed by an extended six-month therapy. Participants treated with CBT initially received maintenance CBT or no additional treatment and those treated with combined therapy initially continued with CBT plus intermittent medication (prn) or CBT without medication (taper). Measures of anxiety and depressive symptoms, fatigue, quality of life, and perceived impact of sleep difficulties on various indices of daytime functioning were completed at baseline, after each treatment stage, and at six-month follow-up. Following acute treatment, significant improvements of fatigue, quality of life (mental component), anxiety, and depression were obtained in the CBT alone condition but not in the combined CBT plus medication condition. Following extended treatment, further improvements were noted for the subgroup receiving extended CBT relative to that with no additional treatment, and for the subgroup receiving CBT and intermittent medication relative to that with CBT but no medication. Improvements were well maintained at the 6-month follow-up. These findings indicate that insomnia-specific therapy is effective at improving daytime and psychological functioning in the short term, and that maintenance therapy produces an added value to optimize long-term outcomes. TRIAL REGISTRATION: www.clinicaltrials.gov (#NCT 00042146). PMID- 27658220 TI - [Management of large litters in piglet production]. AB - In recent years, the number of live-born piglets per litter has increased tremendously. Litters of 15 or even up to 20 piglets are no longer uncommon. Due to this increased fertility, the demands placed on the sows rise as they are expected to rear a large number of healthy and vital piglets until weaning. On the other hand, there is also a higher demand for good management of the sows and litters during the lactation period. To reduce piglet losses, to achieve a high growth performance of piglets in large litters and to maintain the lactating sows in good health and body condition, sows and piglets need to be supported by different management activities during the entire lactation period, which are presented in this article. PMID- 27658221 TI - Serum SPan-1 Is a Significant Risk Factor for Early Recurrence of Pancreatic Cancer after Curative Resection. AB - BACKGROUND/AIMS: Curative resection is still the only treatment for patients with pancreatic ductal adenocarcinoma (PDAC). However, early postoperative recurrence occurs frequently. The aim of this study was to investigate the predictors of early recurrence of PDAC. METHODS: Clinical data of 172 consecutive patients with PDAC who underwent curative resection (R0) between 2000 and 2015 at Tokyo Medical University Hospital were retrospectively analyzed. RESULTS: The median follow-up period was 18.2 months. Recurrence occurred in 96 of 172 (55.8%) patients, 27 in whom recurrence occurred within 6 months (early recurrence). Median survival time of the early recurrence group was 10.7 months. The optimal cutoff concentrations for the prediction of early recurrence were 111.3 U/ml, 3.0 ng/ml, 41 U/ml and 670 U/ml for CA19-9, carcinoembryonic antigen, SPan-1 and DUPAN-2, respectively. Multivariate analysis demonstrated that a SPan-1 concentration of >41 U/ml, having received neoadjuvant therapy and having never received adjuvant chemotherapy were significant and independent predictors of early recurrence. CONCLUSION: A preoperative SPan-1 concentration of >41 U/ml is a significant and independent predictor of the early recurrence of pancreatic adenocarcinoma. PMID- 27658222 TI - Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos. AB - Zinc oxide nanoparticles (nano-ZnO) are one of the most important nanoparticles in the industry. The objectives of this study were (1) to investigate the effects of nano-ZnO on oxidative damage to DNA and on apoptosis in zebrafish (Danio rerio) embryos, and (2) to identify the underlying molecular mechanism affecting theapoptotic process. In addition to nano-ZnO, we also investigated the toxic effects of the Zn2+ ion. Zebrafish embryos were exposed to 10, 30, 60, 90, or 120mg/L nano-ZnO for 96h postfertilization. Nano-ZnO (at concentrations between 10 and 120mg/L) significantly reduced the rate of embryo hatching. Embryos/larvae exposed to 120mg/L nano-ZnO had significantly higher heart rates. Increased heart rates could be a physiological mechanism compensating for body hypoxia. Embryos/larvae exposed to nano-ZnO exhibited oxidative stress, due to an excessive generation of reactive oxygen species (ROS). Oxidative stress was evidenced by increased levels of superoxide dismutase, by increased lipid peroxidation, and by increased expression of genes related to the antioxidant defense system (sod1, cat, gpx1a, and pparalpha), which were altered at different degrees. Upon exposure to nano-ZnO, the percentage of apoptotic cells increased in a dose-dependent manner (0.41% to 4.21%). In addition, altered transcriptional regulation of pro-apoptotic genes (bax, puma, and apaf-1) and anti-apoptotic genes (bcl-2) provided further evidence of the activation of apoptosis. In this study, exposure of zebrafish embryos to nano-ZnO triggered an excessive production of ROS, which was followed by several phenomena: the up-regulation of p53, a reduction in the bcl-2/bax ratio,a reduction in the mitochondrial membrane potential (psim), the release of cytochrome c into the cytosolic fraction, and the activation of caspases 9 and 3. Collectively, our data imply that nano-ZnO induce an excessive production of ROS which then activate the apoptosis pathway mediated by mitochondria and caspases. PMID- 27658223 TI - Home alone-The effects of isolation on uptake of a pharmaceutical contaminant in a social fish. AB - A wide range of biologically active pharmaceutical residues is present in aquatic systems worldwide. As uptake potential and the risk of effects in aquatic wildlife are directly coupled, the aim of this study was to investigate the relationships between stress by isolation, uptake and effects of the psychiatric pharmaceutical oxazepam in fish. To do this, we measured cortisol levels, behavioral stress responses, and oxazepam uptake under different stress and social conditions, in juvenile perch (Perca fluviatilis) that were either exposed (1.03MUgl-1) or not exposed to oxazepam. We found single exposed individuals to take up more oxazepam than individuals exposed in groups, likely as a result of stress caused by isolation. Furthermore, the bioconcentration factor (BCF) was significantly negatively correlated with fish weight in both social treatments. We found no effect of oxazepam exposure on body cortisol concentration or behavioral stress response. Most laboratory experiments, including standardized bioconcentration assays, are designed to minimize stress for the test organisms, however wild animals experience stress naturally. Hence, differences in stress levels between laboratory and natural environments can be one of the reasons why predictions from artificial laboratory experiments largely underestimate uptake of oxazepam, and other pharmaceuticals, in the wild. PMID- 27658224 TI - Dehydroabietic acid cytotoxicity in goldfish radial glial cells in vitro. AB - Dehydroabietic acid (DHAA) is a resin acid present in aquatic environments shown to induce cellular and molecular damage in aquatic animals. In this study, the cytotoxicity of DHAA on primary cultured goldfish radial glial cells (RGCs), an important component of the central nervous system, was evaluated. Here, it is reported that a concentration of 20mg/L DHAA affected cellular morphology and expression of genes involved in RGC steroidogenesis and metabolism. Higher concentration exposures of DHAA (40mg/L) lead to RGC death based on a lactate dehydrogenase leakage assay. Together, these data have implications in understanding the effects of DHAA on an integral central nervous system cell type important for neurogenesis, steroidogenesis and structural support. Due to the continuous presence of DHAA into water systems, results from this study provide indications as to the potential impacts of DHAA and demonstrate the importance of this class of chemicals on aquatic organisms. PMID- 27658225 TI - Road safety performance measures and AADT uncertainty from short-term counts. AB - OBJECTIVE: The objective of this paper is to enable better risk analysis of road safety performance measures by creating the first knowledge base on uncertainty surrounding annual average daily traffic (AADT) estimates when the estimates are derived by expanding short-term counts with the individual permanent counter method. BACKGROUND: Many road safety performance measures and performance models use AADT as an input. While there is an awareness that the input suffers from uncertainty, the uncertainty is not well known or accounted for. METHOD: The paper samples data from a set of 69 permanent automatic traffic recorders in Manitoba, Canada, to simulate almost 2 million short-term counts over a five year period. These short-term counts are expanded to AADT estimates by transferring temporal information from a directly linked nearby permanent count control station, and the resulting AADT values are compared to a known reference AADT to compute errors. The impacts of five factors on AADT error are considered: length of short-term count, number of short-term counts, use of weekday versus weekend counts, distance from a count to its expansion control station, and the AADT at the count site. RESULTS: The mean absolute transfer error for expanded AADT estimates is 6.7%, and this value varied by traffic pattern group from 5% to 10.5%. Reference percentiles of the error distribution show that almost all errors are between -20% and +30%. Error decreases substantially by using a 48-h count instead of a 24-h count, and only slightly by using two counts instead of one. Weekday counts are superior to weekend counts, especially if the count is only 24h. Mean absolute transfer error increases with distance to control station (elasticity 0.121, p=0.001), and increases with AADT (elasticity 0.857, p<0.001). IMPLICATIONS: These results can support evidence-based risk analysis of road safety performance measures that use AADT as inputs. Analytical frameworks for such analysis exist but are infrequently used in road safety because the evidence base on AADT uncertainty is not well developed. PMID- 27658226 TI - Does the probability of DWI arrest fall following participation in DWI and hybrid drug treatment court programs? AB - Using North Carolina administrative data, this study examined recidivism following participation in specialty hybrid drug and driving while intoxicated (DWI) court programs. Three court program participation levels were considered being referred to, enrolling in, and completing a specialty court program. Measures of DWI recidivism were: arrest and total number of arrests for DWI, and being convicted of DWI during follow-up periods of two and, alternatively, four years. Propensity score matching was used to obtain comparable control groups. Using a four-year follow-up, persons convicted of a DWI who completed a specialty court program were associated with a greater reduction in DWI re-arrests and re convictions than did matched individuals who were never referred to a specialty court program. DWI courts were more effective in reducing re-arrests than hybrid drug courts were. Although promising from the vantage point of participants, few persons convicted of a DWI were referred to either court type, thus limiting this strategy's potential effectiveness in reducing DWI. PMID- 27658227 TI - Drivers anticipate lead-vehicle conflicts during automated longitudinal control: Sensory cues capture driver attention and promote appropriate and timely responses. AB - Adaptive Cruise Control (ACC) has been shown to reduce the exposure to critical situations by maintaining a safe speed and headway. It has also been shown that drivers adapt their visual behavior in response to the driving task demand with ACC, anticipating an impending lead vehicle conflict by directing their eyes to the forward path before a situation becomes critical. The purpose of this paper is to identify the causes related to this anticipatory mechanism, by investigating drivers' visual behavior while driving with ACC when a potential critical situation is encountered, identified as a forward collision warning (FCW) onset (including false positive warnings). This paper discusses how sensory cues capture attention to the forward path in anticipation of the FCW onset. The analysis used the naturalistic database EuroFOT to examine visual behavior with respect to two manually-coded metrics, glance location and glance eccentricity, and then related the findings to vehicle data (such as speed, acceleration, and radar information). Three sensory cues (longitudinal deceleration, looming, and brake lights) were found to be relevant for capturing driver attention and increase glances to the forward path in anticipation of the threat; the deceleration cue seems to be dominant. The results also show that the FCW acts as an effective attention-orienting mechanism when no threat anticipation is present. These findings, relevant to the study of automation, provide additional information about drivers' response to potential lead-vehicle conflicts when longitudinal control is automated. Moreover, these results suggest that sensory cues are important for alerting drivers to an impending critical situation, allowing for a prompt reaction. PMID- 27658228 TI - [Correction: The Limits of Selective Laser Trabeculoplasty in Glaucoma Therapy]. PMID- 27658229 TI - Transposed Data in Abstract. PMID- 27658231 TI - Abnormal Optic Nerves in a Healthy Young Woman. PMID- 27658232 TI - Acute Resistance Exercise Performance Is Negatively Impacted by Prior Aerobic Endurance Exercise. AB - Ratamess, NA, Kang, J, Porfido, TM, Ismaili, CP, Selamie, SN, Williams, BD, Kuper, JD, Bush, JA, and Faigenbaum, AD. Acute resistance exercise performance is negatively impacted by prior aerobic endurance exercise. J Strength Cond Res 30(10): 2667-2681, 2016-The purpose of the present study was to examine acute resistance exercise (RE) performance after 4 different aerobic endurance (AE) protocols. Eleven healthy, resistance-trained men (21.0 +/- 1.2 years) performed a control RE protocol and 4 RE protocols 10 minutes after different AE protocols in random sequence. The RE protocol consisted of 5 exercises (high pull, squat, bench press, deadlift, and push press) performed for 3 sets of 6-10 repetitions with 70-80% of one repetition-maximum (1RM) with 3-minute rest intervals in between sets. The AE protocols consisted of treadmill running at velocities corresponding to: (a) 60% of their V[Combining Dot Above]O2 reserve (V[Combining Dot Above]O2R) for 45 minutes (P1); (b) 75% of their V[Combining Dot Above]O2R for 20 minutes (P2); (c) 90-100% of V[Combining Dot Above]O2R in 3-minute intervals (1:1 ratio) for 5 sets (P3); and (d) 75% of V[Combining Dot Above]O2R (4.5 mph) uphill (6-9% grade) for 20 minutes (P4). Completed repetitions, average power and velocity, heart rate (HR), and ratings of perceived exertion (RPE) were assessed each set. Protocols P1-P4 resulted in 9.1-18.6% fewer total repetitions performed compared with the control RE protocol with the squat experiencing the greatest reduction. Average power and velocity were significantly reduced for the high pull, squat, and bench press after most AE protocols. Ratings of perceived exertion values for the high pull and squat were significantly higher in P1-P4 compared with control. Heart rate was significantly higher during RE after P1-P4 compared with control by 4.3-5.5%. These results indicate acute RE performance is significantly compromised in healthy men after AE exercise of different type, intensity, and duration with largest reductions observed after high-intensity interval exercise. PMID- 27658233 TI - Time Course of Changes in Neuromuscular Parameters During Sustained Isometric Muscle Actions. AB - Smith, CM, Housh, TJ, Herda, TJ, Zuniga, JM, Camic, CL, Bergstrom, HC, Smith, DB, Weir, JP, Hill, EC, Cochrane, KC, Jenkins, NDM, Schmidt, RJ, and Johnson, GO. Time course of changes in neuromuscular parameters during sustained isometric muscle actions. J Strength Cond Res 30(10): 2697-2702, 2016-The objective of the present study was to identify the time course of changes in electromyographic (EMG) and mechanomyographic (MMG) time and frequency domain parameters during a sustained isometric muscle action of the leg extensors at 50% maximal voluntary isometric contraction. The EMG and MMG signals were measured from the vastus lateralis of 11 subjects to identify when motor unit activation strategies changed throughout the sustained isometric muscle action. The EMG amplitude (muscle activation) had a positive linear relationship (p = 0.018, r = 0.77) that began to increase at the initiation of the muscle action and continued until task failure. Electromyographic frequency (motor unit action potential conduction velocity) and MMG frequency (global motor unit firing rate) had negative quadratic relationships (p = 0.002, R = 0.99; p = 0.015, R = 0.94) that began to decrease at 30% of the time to exhaustion. The MMG amplitude (motor unit activation) had a cubic relationship (p = 0.001, R = 0.94) that increased from 10 to 30% of the time to exhaustion, then decreased from 40 to 70% of the time to exhaustion, and then markedly increased from 70% to task failure. The time course of changes in the neuromuscular parameters suggested that motor unit activation strategies changed at approximately 30 and 70% of the time to exhaustion during the sustained isometric muscle action. These findings indicate that the time course of changes in neuromuscular responses provide insight into the strategies used to delay the effects of fatigue and are valuable tools for quantifying changes in the fatiguing process during training programs or supplementation research. PMID- 27658230 TI - Age-associated repression of type 1 inositol 1, 4, 5-triphosphate receptor impairs muscle regeneration. AB - Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5 triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies. PMID- 27658234 TI - Implementation of an Ability-Based Training Program in Police Force Recruits. AB - Orr, RM, Ford, K, and Stierli, M. Implementation of an ability-based training program in police force recruits. J Strength Cond Res 30(10): 2781-2787, 2016 Currently, police recruit physical training programs generally use group-based runs of a "1 size fit all" approach. The aim of this study was to assess the impact of an ability-based training (ABT) program, as derived from the 30-15 Intermittent Fitness Assessment, on the metabolic fitness and injury rates of police recruits undergoing basic training. Police recruits completing two different stages of training (session 1: n = 54 and session 2: n = 233) were randomly assigned to either a control group (CG) (standard group running) or an intervention group (IG) (ABT program). Physical training was completed once a week over a 10-week period. Aerobic fitness was measured through 20-m progressive shuttle run test performance. Injury data were captured through formal accident and incident forms. Results found that aerobic fitness was maintained but not significantly improved in both groups for session 1, with no significant differences between the groups after training. In session 2, both groups significantly improved their aerobic fitness (p < 0.001), whereas the IG to a greater degree, with no significant differences between the groups after training. There were no significant differences in injury rates between groups (session 1: chi(1) = 1.533, p = 0.216; session 2: chi(1) = 1.252, p = 0.263). However, the IGs had a significantly lower relative risk (RR) of injury when compared with the CGs (group 1: RR = 0.31, p = 0.28; group 2: RR = 0.59, p = 0.24). The results suggest that coaches may benefit from implementing ABT programs in tactical populations and achieve the same or better fitness gains with a lower risk of injuring recruits. PMID- 27658237 TI - High-resolution melt analysis without DNA extraction affords rapid genotype resolution and species identification. AB - Extracting and sequencing DNA from specimens can impose major time and monetary costs to studies requiring genotyping, or identification to species, of large numbers of individuals. As such, so-called direct PCR methods have been developed enabling significant savings at the DNA extraction step. Similarly, real-time quantitative PCR techniques (qPCR) offer very cost-effective alternatives to sequencing. High-resolution melt analysis (HRM) is a qPCR method that incorporates an intercalating dye into a double-stranded PCR amplicon. The dye fluoresces brightly, but only when it is bound. Thus, after PCR, raising the temperature of the amplicon while measuring the fluorescence of the reaction results in the generation of a sequence-specific melt curve, allowing discrimination of genotypes. Methods combining HRM (or other qPCR methods) and direct PCR have not previously been reported, most likely due to concerns that any tissue in the reaction tube would interfere with detection of the fluorescent signal. Here, we couple direct PCR with HRM and, by way of three examples, demonstrate a very quick and cost-effective method for genotyping large numbers of specimens, using Rotor-Gene HRM instruments (QIAGEN). In contrast to the heated-block design of most qPCR/HRM instruments, the Rotor-Gene's centrifugal rotor and air-based temperature-regulation system facilitate our method by depositing tissues away from the pathway of the machine's fluorescence detection optics. PMID- 27658236 TI - The sequential pathway between trauma-related symptom severity and cognitive based smoking processes through perceived stress and negative affect reduction expectancies among trauma exposed smokers. AB - BACKGROUND AND OBJECTIVES: Smoking rates are markedly higher among trauma-exposed individuals relative to non-trauma-exposed individuals. Extant work suggests that both perceived stress and negative affect reduction smoking expectancies are independent mechanisms that link trauma-related symptoms and smoking. Yet, no work has examined perceived stress and negative affect reduction smoking expectancies as potential explanatory variables for the relation between trauma related symptom severity and smoking in a sequential pathway model. Methods The present study utilized a sample of treatment-seeking, trauma-exposed smokers (n = 363; 49.0% female) to examine perceived stress and negative affect reduction expectancies for smoking as potential sequential explanatory variables linking trauma-related symptom severity and nicotine dependence, perceived barriers to smoking cessation, and severity of withdrawal-related problems and symptoms during past quit attempts. RESULTS: As hypothesized, perceived stress and negative affect reduction expectancies had a significant sequential indirect effect on trauma-related symptom severity and criterion variables. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings further elucidate the complex pathways through which trauma-related symptoms contribute to smoking behavior and cognitions, and highlight the importance of addressing perceived stress and negative affect reduction expectancies in smoking cessation programs among trauma exposed individuals. (Am J Addict 2016;25:565-572). PMID- 27658235 TI - Current Heavy Alcohol Consumption is Associated with Greater Cognitive Impairment in Older Adults. AB - BACKGROUND: The acute consumption of excessive quantities of alcohol causes well recognized neurophysiological and cognitive alterations. As people reach advanced age, they are more prone to cognitive decline. To date, the interaction of current heavy alcohol (ethanol [EtOH]) consumption and aging remains unclear. This study tested the hypothesis that negative consequences of current heavy alcohol consumption on neurocognitive function are worse with advanced age. Further, we evaluated the relations between lifetime history of alcohol dependence and neurocognitive function METHODS: Sixty-six participants underwent a comprehensive neurocognitive battery. Current heavy EtOH drinkers were classified using National Institute on Alcohol Abuse and Alcoholism criteria (EtOH heavy, n = 21) based on the Timeline follow-back and a structured clinical interview and compared to nondrinkers, and moderate drinkers (EtOH low, n = 45). Of the total population, 53.3% had a lifetime history of alcohol dependence. Neurocognitive data were grouped and analyzed relative to global and domain scores assessing: global cognitive function, attention/executive function, learning, memory, motor function, verbal function, and speed of processing. RESULTS: Heavy current EtOH consumption in older adults was associated with poorer global cognitive function, learning, memory, and motor function (ps < 0.05). Furthermore, lifetime history of alcohol dependence was associated with poorer function in the same neurocognitive domains, in addition to the attention/executive domain, irrespective of age (ps < 0.05). CONCLUSIONS: These data suggest that while heavy current alcohol consumption is associated with significant impairment in a number of neurocognitive domains, history of alcohol dependence, even in the absence of heavy current alcohol use, is associated with lasting negative consequences for neurocognitive function. PMID- 27658239 TI - Pyoderma gangrenosum with extensive pulmonary involvement. PMID- 27658238 TI - The Effect of Exercise Training on Resting Concentrations of Peripheral Brain Derived Neurotrophic Factor (BDNF): A Meta-Analysis. AB - BACKGROUND: The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain derived neurotrophic factor (BDNF) mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood. METHODS: MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions >= 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses. RESULTS: In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17-0.60, p < 0.001). Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33-0.99, p < 0.001) but not resistance training (SMD = 0.07, 95% CI: -0.15-0.30, p = 0.52) interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma. CONCLUSION: Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood. PMID- 27658240 TI - Autophagy as a Survival Mechanism for Squamous Cell Carcinoma Cells in Endonuclease G-Mediated Apoptosis. AB - Safingol, L- threo-dihydrosphingosine, induces cell death in human oral squamous cell carcinoma (SCC) cells through an endonuclease G (endoG) -mediated pathway. We herein determined whether safingol induced apoptosis and autophagy in oral SCC cells. Safingol induced apoptotic cell death in oral SCC cells in a dose dependent manner. In safingol-treated cells, microtubule-associated protein 1 light chain 3 (LC3)-I was changed to LC3-II and the cytoplasmic expression of LC3, amount of acidic vesicular organelles (AVOs) stained by acridine orange and autophagic vacuoles were increased, indicating the occurrence of autophagy. An inhibitor of autophagy, 3-methyladenine (3-MA), enhanced the suppressive effects of safingol on cell viability, and this was accompanied by an increase in the number of apoptotic cells and extent of nuclear fragmentation. The nuclear translocation of endoG was minimal at a low concentration of safingol, but markedly increased when combined with 3-MA. The suppressive effects of safingol and 3-MA on cell viability were reduced in endoG siRNA- transfected cells. The scavenging of reactive oxygen species (ROS) prevented cell death induced by the combinational treatment, whereas a pretreatment with a pan-caspase inhibitor z VAD-fmk did not. These results indicated that safingol induced apoptosis and autophagy in SCC cells and that the suppression of autophagy by 3-MA enhanced apoptosis. Autophagy supports cell survival, but not cell death in the SCC cell system in which apoptosis occurs in an endoG-mediated manner. PMID- 27658242 TI - Living donor robotic right hepatectomy is the future: Or is it? PMID- 27658241 TI - Genome-Wide Comparison of Magnaporthe Species Reveals a Host-Specific Pattern of Secretory Proteins and Transposable Elements. AB - Blast disease caused by the Magnaporthe species is a major factor affecting the productivity of rice, wheat and millets. This study was aimed at generating genomic information for rice and non-rice Magnaporthe isolates to understand the extent of genetic variation. We have sequenced the whole genome of the Magnaporthe isolates, infecting rice (leaf and neck), finger millet (leaf and neck), foxtail millet (leaf) and buffel grass (leaf). Rice and finger millet isolates infecting both leaf and neck tissues were sequenced, since the damage and yield loss caused due to neck blast is much higher as compared to leaf blast. The genome-wide comparison was carried out to study the variability in gene content, candidate effectors, repeat element distribution, genes involved in carbohydrate metabolism and SNPs. The analysis of repeat element footprints revealed some genes such as naringenin, 2-oxoglutarate 3-dioxygenase being targeted by Pot2 and Occan, in isolates from different host species. Some repeat insertions were host-specific while other insertions were randomly shared between isolates. The distributions of repeat elements, secretory proteins, CAZymes and SNPs showed significant variation across host-specific lineages of Magnaporthe indicating an independent genome evolution orchestrated by multiple genomic factors. PMID- 27658243 TI - Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization - Mass Spectrometry Imaging. AB - Desorption electrospray ionization-mass spectrometry (DESI-MS) imaging was used to analyze unmodified human brain tissue sections from 39 subjects sequentially in the positive and negative ionization modes. Acquisition of both MS polarities allowed more complete analysis of the human brain tumor lipidome as some phospholipids ionize preferentially in the positive and others in the negative ion mode. Normal brain parenchyma, comprised of grey matter and white matter, was differentiated from glioma using positive and negative ion mode DESI-MS lipid profiles with the aid of principal component analysis along with linear discriminant analysis. Principal component-linear discriminant analyses of the positive mode lipid profiles was able to distinguish grey matter, white matter, and glioma with an average sensitivity of 93.2% and specificity of 96.6%, while the negative mode lipid profiles had an average sensitivity of 94.1% and specificity of 97.4%. The positive and negative mode lipid profiles provided complementary information. Principal component-linear discriminant analysis of the combined positive and negative mode lipid profiles, via data fusion, resulted in approximately the same average sensitivity (94.7%) and specificity (97.6%) of the positive and negative modes when used individually. However, they complemented each other by improving the sensitivity and specificity of all classes (grey matter, white matter, and glioma) beyond 90% when used in combination. Further principal component analysis using the fused data resulted in the subgrouping of glioma into two groups associated with grey and white matter, respectively, a separation not apparent in the principal component analysis scores plots of the separate positive and negative mode data. The interrelationship of tumor cell percentage and the lipid profiles is discussed, and how such a measure could be used to measure residual tumor at surgical margins. PMID- 27658244 TI - Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow. AB - Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment. PMID- 27658245 TI - Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis. AB - The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa-induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice that are typically resistant to P. aeruginosa induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found to be dependent on both eye and gut microbiota with the eye microbiota having a moderate, but significant impact on the resistance to infection. These events were IL-1beta-dependent as corneal IL-1beta levels were decreased in the infected GF and antibiotic-treated mice when compared to the SPF controls, and neutralization of IL-1beta increased the ocular bacterial burden in the SPF mice. Monocolonizing GF mice with Coagulase Negative Staphylococcus sp. isolated from the conjunctival swabs was sufficient to restore resistance to infection. Cumulatively, these data underline a previously unappreciated role for microbiota in regulating susceptibility to ocular keratitis. We predict that these results will have significant implications for contact lens wearers, where alterations in the ocular commensal communities may render the ocular surface vulnerable to infections. PMID- 27658246 TI - An Experimental Evolution Test of the Relationship between Melanism and Desiccation Survival in Insects. AB - We used experimental evolution to test the 'melanism-desiccation' hypothesis, which proposes that dark cuticle in several Drosophila species is an adaptation for increased desiccation tolerance. We selected for dark and light body pigmentation in replicated populations of D. melanogaster and assayed several traits related to water balance. We also scored pigmentation and desiccation tolerance in populations selected for desiccation survival. Populations in both selection regimes showed large differences in the traits directly under selection. However, after over 40 generations of pigmentation selection, dark selected populations were not more desiccation-tolerant than light-selected and control populations, nor did we find significant changes in mass or carbohydrate amounts that could affect desiccation resistance. Body pigmentation of desiccation-selected populations did not differ from control populations after over 140 generations of selection, although selected populations lost water less rapidly. Our results do not support an important role for melanization in Drosophila water balance. PMID- 27658247 TI - Constructing an Invasion Machine: The Rapid Evolution of a Dispersal-Enhancing Phenotype During the Cane Toad Invasion of Australia. AB - Biological invasions can induce rapid evolutionary change. As cane toads (Rhinella marina) have spread across tropical Australia over an 80-year period, their rate of invasion has increased from around 15 to 60 km per annum. Toads at the invasion front disperse much faster and further than conspecifics from range core areas, and their offspring inherit that rapid dispersal rate. We investigated morphological changes that have accompanied this dramatic acceleration, by conducting three-dimensional morphometric analyses of toads from both range-core and invasion-front populations. Morphology of heads, limbs, pectoral girdles and pelvic girdles differed significantly between toads from the two areas, ranging from 0.5% to 16.5% difference in mean bone dimensions between populations, with invasion-front toads exhibiting wider forelimbs, narrower hindlimbs and more compact skulls. Those changes plausibly reflect an increased reliance on bounding (multiple short hops in quick succession) rather than separate large leaps. Within an 80-year period, invasive cane toads have converted the basic anuran body plan - which evolved for occasional large leaps to evade predators - into a morphotype better-suited to sustained long-distance travel. PMID- 27658248 TI - A Comparative Study of Three Interneuron Types in the Rat Spinal Cord. AB - Interneurons are involved in the physiological function and the pathomechanism of the spinal cord. Present study aimed to examine and compare the characteristics of Cr+, Calb+ and Parv+ interneurons in morphology and distribution by using immunhistochemical and Western blot techniques. Results showed that 1) Cr-Calb presented a higher co-existence rate than that of Cr-Parv, and both of them were higher in the ventral horn than in the dosal horn; 2) Cr+, Calb+ and Parv+ neurons distributing zonally in the superficial dosal horn were small-sized. Parv+ neuronswere the largest, and Cr+ and Calb+ neurons were higher density among them. In the deep dorsal horn, Parv+ neurons were mainly located in nucleus thoracicus and the remaining scatteredly distributed. Cr+ neuronal size was the largest, and Calb+ neurons were the least among three interneuron types; 3) Cr+, Calb+ and Parv+ neurons of ventral horns displayed polygonal, round and fusiform, and Cr+ and Parv+ neurons were mainly distributed in the deep layer, but Calb+ neurons mainly in the superficial layer. Cr+ neurons were the largest, and distributed more in ventral horns than in dorsal horns; 4) in the dorsal horn of lumbar cords, Calb protein levels was the highest, but Parv protein level in ventral horns was the highest among the three protein types. Present results suggested that the morphological characteristics of three interneuron types imply their physiological function and pathomechanism relevance. PMID- 27658249 TI - Identification of Non-Coding RNAs in the Candida parapsilosis Species Group. AB - The Candida CTG clade is a monophyletic group of fungal species that translates CTG as serine, and includes the pathogens Candida albicans and Candida parapsilosis. Research has typically focused on identifying protein-coding genes in these species. Here, we use bioinformatic and experimental approaches to annotate known classes of non-coding RNAs in three CTG-clade species, Candida parapsilosis, Candida orthopsilosis and Lodderomyces elongisporus. We also update the annotation of ncRNAs in the C. albicans genome. The majority of ncRNAs identified were snoRNAs. Approximately 50% of snoRNAs (including most of the C/D box class) are encoded in introns. Most are within mono- and polycistronic transcripts with no protein coding potential. Five polycistronic clusters of snoRNAs are highly conserved in fungi. In polycistronic regions, splicing occurs via the classical pathway, as well as by nested and recursive splicing. We identified spliceosomal small nuclear RNAs, the telomerase RNA component, signal recognition particle, RNase P RNA component and the related RNase MRP RNA component in all three genomes. Stem loop IV of the U2 spliceosomal RNA and the associated binding proteins were lost from the ancestor of C. parapsilosis and C. orthopsilosis, following the divergence from L. elongisporus. The RNA component of the MRP is longer in C. parapsilosis, C. orthopsilosis and L. elongisporus than in S. cerevisiae, but is substantially shorter than in C. albicans. PMID- 27658250 TI - A Total Pleural Covering for Lymphangioleiomyomatosis Prevents Pneumothorax Recurrence. AB - BACKGROUND: Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. METHODS: Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. RESULTS: TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 +/- 0.606 episode/month (mean +/- SD) before TPC vs. 0.008 +/- 0.019 after TPC (P<0.0001). Grade IIIa postoperative complications were found in 13 TPC surgeries (24.1%). CONCLUSIONS: TPC successfully prevented the recurrence of pneumothorax in LAM, was minimally invasive and rarely caused restrictive ventilatory impairment. PMID- 27658251 TI - Taxonomic Identity Resolution of Highly Phylogenetically Related Strains and Selection of Phylogenetic Markers by Using Genome-Scale Methods: The Bacillus pumilus Group Case. AB - Bacillus pumilus group strains have been studied due their agronomic, biotechnological or pharmaceutical potential. Classifying strains of this taxonomic group at species level is a challenging procedure since it is composed of seven species that share among them over 99.5% of 16S rRNA gene identity. In this study, first, a whole-genome in silico approach was used to accurately demarcate B. pumilus group strains, as a case of highly phylogenetically related taxa, at the species level. In order to achieve that and consequently to validate or correct taxonomic identities of genomes in public databases, an average nucleotide identity correlation, a core-based phylogenomic and a gene function repertory analyses were performed. Eventually, more than 50% such genomes were found to be misclassified. Hierarchical clustering of gene functional repertoires was also used to infer ecotypes among B. pumilus group species. Furthermore, for the first time the machine-learning algorithm Random Forest was used to rank genes in order of their importance for species classification. We found that ybbP, a gene involved in the synthesis of cyclic di-AMP, was the most important gene for accurately predicting species identity among B. pumilus group strains. Finally, principal component analysis was used to classify strains based on the distances between their ybbP genes. The methodologies described could be utilized more broadly to identify other highly phylogenetically related species in metagenomic or epidemiological assessments. PMID- 27658252 TI - Chronic Periprosthetic Hip Joint Infection. A Retrospective, Observational Study on the Treatment Strategy and Prognosis in 130 Non-Selected Patients. AB - INTRODUCTION: Limited information is available regarding the treatment strategy and prognosis of non-selected patients treated for chronic periprosthetic hip joint infection. Such information is important as no head-to-head studies on treatment strategies are available. The purpose of this study is to report on the treatment strategy and prognosis of a non-selected, consecutive patient population. METHODS: We identified 130 patients in the National Patient Registry, consecutively treated for a chronic periprosthetic hip joint infection between 2003-2008 at 11 departments of orthopaedic surgery. We extracted information regarding patient demographics, treatment and outcome. 82 patients were re implanted in a two-stage revision (national standard), the remaining 48 were not re-implanted in a two-stage revision. We were able to collect up-to-date information on all patients to date of death or medical chart review with a minimum of 5 years follow-up by the nationwide electronic patient record system. RESULTS: After primary revision surgery, 53 patients (41%) had a spacer in situ, 64 (50%) had a resection arthroplasty and 13 (9%) did not have the infected implant removed. 63% were re-implanted in a two-stage revision. Re-implantation was performed after an interim period of 14 weeks (IQR 10-18). Patients re implanted were younger (p-value 0.0006), had a lower CCS score (p-value 0.005), a lower ASA score (p-value 0.0001) and a 68% lower mortality risk in the follow-up period (p-value <0.00001). After adjusting for selected confounders, the mortality risk was no longer significantly different. The 5-year re-infection rate after re-implantation was 14.6% (95%CI 8.0-23.1). Re-infections occurred mainly within 3 years of follow-up. The overall 1-year survival rate was 92% (95%CI 86-96) and the overall 5-year survival rate was 68% (95%CI 59-75). The 5 year survival rate after a two-stage revision was 82% (95%CI 71-89) and in those not re-implanted 45% (95%CI 30-58). CONCLUSION: We found that patients who receive a two-stage revision after a chronic periprosthetic hip joint infection are younger and healthier when compared to those who do not receive a two-stage revision in a non-selected patient population, indicating a clear selection of patients into this treatment strategy. Re-infection rates following two-stage revision were comparable to international results. We found a high mortality rate in our study population, but the causality of death and chronic periprosthetic hip joint infection cannot be established in this study and this needs further attention. PMID- 27658253 TI - Electrode Mass Balancing as an Inexpensive and Simple Method to Increase the Capacitance of Electric Double-Layer Capacitors. AB - Symmetric electric double-layer capacitors (EDLCs) have equal masses of the same active material in both electrodes. However, having equal electrode masses may prevent the EDLC to have the largest possible specific capacitance if the sizes of the hydrated anions and cations in the electrolyte differ because the electrodes and the electrolyte may not be completely utilized. Here we demonstrate how this issue can be resolved by mass balancing. If the electrode masses are adjusted according to the size of the ions, one can easily increase an EDLC's specific capacitance. To that end, we performed galvanostatic cycling to measure the capacitances of symmetric EDLCs with different electrode mass ratios using four aqueous electrolytes- Na2SO4, H2SO4, NaOH, and KOH (all with a concentration of 1 M)-and compared these to the theoretical optimal electrode mass ratio that we calculated using the sizes of the hydrated ions. Both the theoretical and experimental values revealed lower-than-1 optimal electrode ratios for all electrolytes except KOH. The largest increase in capacitance was obtained for EDLCs with NaOH as electrolyte. Specifically, we demonstrate an increase of the specific capacitance by 8.6% by adjusting the electrode mass ratio from 1 to 0.86. Our findings demonstrate that electrode mass balancing is a simple and inexpensive method to increase the capacitance of EDLCs. Furthermore, our results imply that one can reduce the amount of unused material in EDLCs and thus decrease their weight, volume and cost. PMID- 27658254 TI - The Panitumumab EGFR Complex Reveals a Binding Mechanism That Overcomes Cetuximab Induced Resistance. AB - Panitumumab and cetuximab target the epidermal growth factor receptor for the treatment of metastatic colorectal cancer. These therapies provide a significant survival benefit to patients with metastatic colorectal cancer with wild-type RAS. A single point mutation in the ectodomain of EGFR (S468R) confers acquired or secondary resistance in cetuximab treated patients, which is not observed in panitumumab-treated patients. Structural and biophysical studies presented here show this mutation directly blocks cetuximab binding to EGFR domain III and describes a unique mechanism by which panitumumab uses a central cavity to accommodate this mutation. PMID- 27658255 TI - Serum Soluble Corin Deficiency Predicts Major Disability within 3 Months after Acute Stroke. AB - OBJECTIVE: Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke. METHODS: We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype. RESULTS: Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes. CONCLUSION: Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis. PMID- 27658256 TI - Distribution and Diversity of Bacteria and Fungi Colonization in Stone Monuments Analyzed by High-Throughput Sequencing. AB - The historical and cultural heritage of Qingxing palace and Lingyin and Kaihua temple, located in Hangzhou of China, include a large number of exquisite Buddhist statues and ancient stone sculptures which date back to the Northern Song (960-1219 A.D.) and Qing dynasties (1636-1912 A.D.) and are considered to be some of the best examples of ancient stone sculpting techniques. They were added to the World Heritage List in 2011 because of their unique craftsmanship and importance to the study of ancient Chinese Buddhist culture. However, biodeterioration of the surface of the ancient Buddhist statues and white marble pillars not only severely impairs their aesthetic value but also alters their material structure and thermo-hygric properties. In this study, high-throughput sequencing was utilized to identify the microbial communities colonizing the stone monuments. The diversity and distribution of the microbial communities in six samples collected from three different environmental conditions with signs of deterioration were analyzed by means of bioinformatics software and diversity indices. In addition, the impact of environmental factors, including temperature, light intensity, air humidity, and the concentration of NO2 and SO2, on the microbial communities' diversity and distribution was evaluated. The results indicate that the presence of predominantly phototrophic microorganisms was correlated with light and humidity, while nitrifying bacteria and Thiobacillus were associated with NO2 and SO2 from air pollution. PMID- 27658257 TI - Ethyl Pyruvate: An Anti-Microbial Agent that Selectively Targets Pathobionts and Biofilms. AB - The microbiota has a strong influence on health and disease in humans. A causative shift favoring pathobionts is strongly linked to diseases. Therefore, anti-microbial agents selectively targeting potential pathogens as well as their biofilms are urgently demanded. Here we demonstrate the impact of ethyl pyruvate, so far known as ROS scavenger and anti-inflammatory agent, on planktonic microbes and biofilms. Ethyl pyruvate combats preferably the growth of pathobionts belonging to bacteria and fungi independent of the genera and prevailing drug resistance. Surprisingly, this anti-microbial agent preserves symbionts like Lactobacillus species. Moreover, ethyl pyruvate prevents the formation of biofilms and promotes matured biofilms dissolution. This potentially new anti microbial and anti-biofilm agent could have a tremendous positive impact on human, veterinary medicine and technical industry as well. PMID- 27658259 TI - Correction: Microneutralization Assay Titres Correlate with Protection against Seasonal Influenza H1N1 and H3N2 in Children. AB - [This corrects the article DOI: 10.1371/journal.pone.0131531.]. PMID- 27658258 TI - Colony Level Prevalence and Intensity of Nosema ceranae in Honey Bees (Apis mellifera L.). AB - Nosema ceranae is a widely prevalent microsporidian parasite in the western honey bee. There is considerable uncertainty regarding infection dynamics of this important pathogen in honey bee colonies. Understanding the infection dynamics at the colony level may aid in development of a reliable sampling protocol for N. ceranae diagnosis, and provide insights into efficient treatment strategies. The primary objective of this study was to characterize the prevalence (proportion of the sampled bees found infected) and intensity (number of spores per bee) of N. ceranae infection in bees from various age cohorts in a colony. We examined N. ceranae infection in both overwintered colonies that were naturally infected with N. ceranae and in quadruple cohort nucleus colonies that were established and artificially inoculated with N. ceranae. We also examined and quantified effects of N. ceranae infection on hypopharyngeal gland protein content and gut pH. There was no correlation between the prevalence and intensity of N. ceranae infection in composite samples (pooled bee samples used for analysis). Our results indicated that the prevalence and intensity of N. ceranae infection is significantly influenced by honey bee age. The N. ceranae infection prevalence values from composite samples of background bees (unmarked bees collected from four different locations in a colony) were not significantly different from those pertaining to marked-bee age cohorts specific to each sampling date. The foraging aged bees had a higher prevalence of N. ceranae infection when compared to nurse aged bees. N. ceranae did not have a significant effect on hypopharyngeal gland protein content. Further, there was no significant difference in mean gut pH of N. ceranae infected bees and non-infected bees. This study provides comprehensive insights into N. ceranae infection dynamics at the colony level, and also demonstrates the effects of N. ceranae infection on hypopharyngeal gland protein content and midgut pH. PMID- 27658260 TI - DRPPP: A machine learning based tool for prediction of disease resistance proteins in plants. AB - Plant disease outbreak is increasing rapidly around the globe and is a major cause for crop loss worldwide. Plants, in turn, have developed diverse defense mechanisms to identify and evade different pathogenic microorganisms. Early identification of plant disease resistance genes (R genes) can be exploited for crop improvement programs. The present prediction methods are either based on sequence similarity/domain-based methods or electronically annotated sequences, which might miss existing unrecognized proteins or low similarity proteins. Therefore, there is an urgent need to devise a novel machine learning technique to address this problem. In the current study, a SVM-based tool was developed for prediction of disease resistance proteins in plants. All known disease resistance (R) proteins (112) were taken as a positive set, whereas manually curated negative dataset consisted of 119 non-R proteins. Feature extraction generated 10,270 features using 16 different methods. The ten-fold cross validation was performed to optimize SVM parameters using radial basis function. The model was derived using libSVM and achieved an overall accuracy of 91.11% on the test dataset. The tool was found to be robust and can be used for high-throughput datasets. The current study provides instant identification of R proteins using machine learning approach, in addition to the similarity or domain prediction methods. PMID- 27658261 TI - Influence of gray level and space discretization on brain tumor heterogeneity measures obtained from magnetic resonance images. AB - PURPOSE: Tumor heterogeneity in medical imaging is a current research trend due to its potential relationship with tumor malignancy. The aim of this study is to analyze the effect of dynamic range and matrix size changes on the results of different heterogeneity measures. MATERIALS AND METHODS: Four patients harboring three glioblastomas and one metastasis were considered. Sixteen textural heterogeneity measures were computed for each patient, with a configuration including co-occurrence matrices (CM) features (local heterogeneity) and run length matrices (RLM) features (regional heterogeneity). The coefficient of variation measured agreement between the textural measures in two types of experiments: (i) fixing the matrix size and changing the dynamic range and (ii) fixing the dynamic range and changing the matrix size. RESULTS: None of the measures considered were robust under dynamic range changes. The CM Entropy and the RLM high gray-level run emphasis (HGRE) were the outstanding textural features due to their robustness under matrix size changes. Also, the RLM low gray-level run emphasis (LGRE) provided robust results when the dynamic range considered was sufficiently high (more than 8 levels). All of the remaining textural features were not robust. CONCLUSION: Tumor texture studies based on images with different characteristics (e.g. multi-center studies) should first fix the dynamic range to be considered. For studies involving images of different resolutions either (i) only robust measures should be used (in our study CM entropy, RLM HGRE and/or RLM LGRE) or (ii) images should be resampled to match those of the lowest resolution before computing the textural features. PMID- 27658262 TI - Observer performance in characterization of carotid plaque texture and surface characteristics with 3D versus 2D ultrasound. AB - OBJECTIVE: To determine the reproducibility of three-dimensional (3D) ultrasound (US) over two-dimensional (2D) US in characterizing atherosclerotic carotid plaques using inter- and intra-observer agreement metrics. METHODS: A Total of 51 patients with 105 carotid artery plaques were screened using 3D and 2D US probes attached to the same US scanner. Two independent observers characterized the plaques based on the morphological features namely echotexture, echogenicity and surface characteristics. The scores assigned to each morphological feature were used to determine intra- and inter-observer performance. The level of agreement was measured using Kappa coefficient. RESULTS: The first observer with 2D US showed fair (k=0.4-0.59) and very strong (k>0.8) with 3D US intra-observer agreements using three morphological features. The second observer indicated moderate strong (k=0.6-0.79) with 2D US and very strong with 3D US (k>0.8) intra observer performances. Moderate strong (k=0.6-0.79) and very strong (k>0.8) inter observer agreements were reported with 2D US and 3D US respectively. The results with 2D and 3D US were correlated 62% using only echotexture and 56% using surface morphology coupled with echogenicity. 3D US gave a lower score than 2D 71% of the time (p=0.005) in disagreement cases. CONCLUSION: High reproducibility in carotid plaque characterization was obtained using 3D US rather than 2D US. Hence, it can be a preferred imaging modality in routine or follow up plaque screening of patients with carotid artery disease. PMID- 27658263 TI - Evaluation of Effects of Topical Estradiol Benzoate Application on Cutaneous Wound Healing in Ovariectomized Female Mice. AB - Estrogen promotes cutaneous wound healing in ovariectomized (OVX) female mice. However, the effects of topical estrogen application on wounds remain unclear. Therefore, the aim of this study was to compare the effects of topical estrogen application on wounds with standard treatment methods. Eight-week-old C57BL/6J female mice underwent OVX and received two full-thickness wounds four weeks later. Mice were divided into three groups: topical estradiol benzoate (EB) (0.75 MUg/g/day) wound treatment, subcutaneous estradiol (E2) pellets (0.05 mg, 21 days), and topical E2 (0.01 g/day) skin application. Wound healing was observed until day 14. Wound area ratios were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet group on days 1-14 (p < 0.05) and topical E2 skin application group on days 1-9 (p < 0.05). Neutrophil and macrophage numbers were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 skin application groups on day 7 (p < 0.05). Moreover, the number of new blood vessels and ratio of myofibroblasts were significantly larger in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 application skin groups on day 7 (p < 0.05). These results demonstrate that the application of estrogen to wounds reduced inflammatory responses and promoted angiogenesis and wound contraction more than the two other standard treatment methods. PMID- 27658264 TI - Children with developmental coordination disorder (DCD) can adapt to perceptible and subliminal rhythm changes but are more variable. AB - Children with DCD demonstrate impairments in bimanual finger tapping during self paced tapping and tapping in synchrony to different frequencies. In this study, we investigated the ability of children with DCD to adapt motorically to perceptible or subliminal changes of the auditory stimuli without a change in frequency, and compared their performance to typically developing controls (TDC). Nineteen children with DCD between ages 6-11years (mean age+/-SD=114+/-21months) and 17 TDC (mean age+/-SD=113+/-21months) participated in this study. Auditory perceptual threshold was established. Children initially tapped bimanually to an antiphase beat and then to either a perceptible change in rhythm or to gradual subliminal changes in rhythm. Children with DCD were able to perceive changes in rhythm similar to TDC. They were also able to adapt to both perceptible and subliminal changes in rhythms similar to their age- and gender- matched TDC. However, these children were significantly more variable compared with TDC in all phasing conditions. The results suggest that the performance impairments in bilateral tapping are not a result of poor conscious or sub-conscious perception of the auditory cue. The increased motor variability may be associated with cerebellar dysfunction but further behavioral and neurophysiological studies are needed. PMID- 27658266 TI - Attention-Deficit/Hyperactivity Disorder and Lifestyle-Related Behaviors in Children. AB - Attention-deficit/hyperactivity disorder (ADHD) has been associated with obesity in children. Lifestyle-related behaviors (external eating, screen time and physical inactivity) are well known to be associated with increased risk of obesity, but their associations with ADHD are unclear. The objectives of this study were to clarify the associations between ADHD symptoms in children and their associated lifestyle. A cross sectional study was carried out with a total of 785 primary students aged 9 to 13 years old and their parents were recruited by stratified random sampling from primary schools of China. The Cochran-Mantel Haenszel (CMH) test was used to examine the relationships between ADHD symptoms and health related behaviors. We found that children with ADHD symptoms were likely to spend more time using a computer during school days; they were also more likely to eat while using a computer. These children were also more likely to eat while seated in a car, using a smart phone, using a computer at bedtime, and snacking before going to sleep than children without ADHD symptoms. An increased risk of obesity in children with ADHD symptoms was associated with the overuse of electronic devices, eating while using electronic devices, and delaying bedtimes to snack and use electronic devices. PMID- 27658265 TI - Localization, Shedding, Regulation and Function of Aminopeptidase N/CD13 on Fibroblast like Synoviocytes. AB - Aminopeptidase N/CD13 is highly expressed by fibroblast like synoviocytes (FLS) and may play a role in rheumatoid arthritis (RA). CD13 was previously detected in human synovial fluid where it was significantly increased in RA compared to osteoarthritis. In this study we found that CD13 in biological fluids (plasma, synovial fluid, FLS culture supernatant) is present as both a soluble molecule and on extracellular vesicles, including exosomes, as assessed by differential ultracentrifugation and density gradient separation. Having determined CD13 could be released as a soluble molecule from FLS, we examined potential mechanisms by which CD13 might be shed from the FLS membrane. The use of protease inhibitors revealed that CD13 is cleaved from the FLS surface by metalloproteinases. siRNA treatment of FLS revealed one of those proteases to be MMP14. We determined that pro-inflammatory cytokines (TNFalpha, IFNgamma, IL-17) upregulated CD13 mRNA in FLS, which may contribute to the increased CD13 in RA synovium and synovial fluid. Inhibition of CD13 function by either inhibitors of enzymatic activity or anti-CD13 antibodies resulted in decreased growth and diminished migration of FLS. This suggests that CD13 may be involved in the pathogenic hyperplasia of RA FLS. This data expands potential roles for CD13 in the pathogenesis of RA. PMID- 27658268 TI - [Diagnostic imaging of changes of the canine intervertebral disc]. AB - Intervertebral disc degeneration can cause intervertebral disc herniation. Diagnostic imaging, including radiography, computed tomography and magnetic resonance imaging, is the most important tool in diagnosis. Firstly, an overview of macroscopic and biochemical physiology and pathology of the intervertebral disc will be given. Subsequently, the physics of diagnostic imaging and the appearance of intervertebral disc degeneration and displacement in several imaging methods are described. PMID- 27658267 TI - Engineered transmembrane pores. AB - Today, hundreds of researchers are working on nanopores, making an impact in both basic science and biotechnology. Proteins remain the most versatile sources of nanopores, based on our ability to engineer them with sub-nanometer precision. Recent work aimed at the construction and discovery of novel pores has included unnatural amino acid mutagenesis and the application of selection techniques. The diversity of structures has now been increased through the development of helix based pores as well as the better-known beta barrels. New developments also include truncated pores, which pierce bilayers through lipid rearrangement, and hybrid pores, which do away with bilayers altogether. Pore dimers, which span two lipid bilayers, have been constructed and pores based on DNA nanostructures are gaining in importance. While nanopore DNA sequencing has received enthusiastic attention, protein pores have a wider range of potential applications, requiring specifications that will require engineering efforts to continue for years to come. PMID- 27658270 TI - Prof. Thomas Buchner (22 September 1934-5 August 2016). A career devoted to research in acute myeloid leukaemia. PMID- 27658271 TI - 'Failure to Maintain': A theoretical proposition for a new quality indicator of nurse care rationing for complex older people in hospital. AB - Complex older patients represent about half of all acute public hospital admissions in Australia. People with dementia are a classic example of complex older patients, and have been identified to have higher rates of hospital acquired complications. Complications contribute to poorer patient outcomes, and increase length of stay and cost to hospitals. The care for older people with dementia is complex, and this has been attributed to: their cognitive response to being hospitalised; their limited ability to self-care; and lack of nursing engagement with the family caregiver. Registered nurses can offer simultaneous assessment and intervention to prevent or mitigate hospital-acquired complications. However, it is known that when demand for nursing care exceeds supply, care is prioritised according to acute medical need. Consequently some basic but essential nursing care activities such as patient mobility, communication, skin care, hydration and nutrition are implicitly rationed. This paper offers a theoretical proposition of 'Failure to Maintain' as a conceptual framework to indicate implicit care rationing by nurses. Care rationing contributes to functional and cognitive decline of complex older patients, which then contributes to higher rates of hospital acquired complications. Four key hospital acquired complications: pressure injuries, pneumonia, urinary tract infections and delirium are proposed as measurable indicators of 'Failure to Maintain'. Hospital focus on throughput constrains nurses to privilege predictable, solvable and medically-related procedures and processes that will lead to efficient discharge over patient mobility, communication, skin care, hydration and nutrition. This privileging, also known as implicit rationing, is theoretically and physiologically associated with a rise in the incidence of complications such as pressure injuries, pneumonia, urinary tract infection, and delirium. Complex older patients, including those with dementia, are at higher risk of the complications, therefore should have higher delivery of prophylactic intervention (ie have higher care needs). 'Failure to Maintain' offers a conceptual framework that is inclusive of, and sensitive to, this vulnerable population. Implicit rationing is occurring and it likely contributes to functional and cognitive decline in complex older patients and hospital-acquired complications. However, the lack of patient functional ability data at admission and discharge for hospitalised patients, and lack of usable ward and hospital level nurse staffing and workload data makes it difficult to monitor, understand and improve quality of care. Current research in the fields of acute geriatrics and nursing work environments show promise through enabling multidisciplinary team communication, and facilitating clinical autonomy to provide patient focussed care, and avoid 'Failing to Maintain'. The research field of acute geriatrics can understand and act on the risk modification role of nurses, including controlling for nurse staffing and work environment variables in intervention studies. The research field of nurse sensitive outcomes should incorporate the different profile of complex older patients, by including age brackets and functional ability as variables in their studies. Clinically, nursing work environments can be designed to recognise the different profile of complex older patients by adapting practices to privilege mobility, hydration, nutrition, skin care and communication in the midst of acute care interventions. PMID- 27658272 TI - [Es war die richtige Entscheidung, den Gentest machen zu lassen - Erfahrungsbericht einer Patientin]. PMID- 27658269 TI - Resistance to imatinib in patients with chronic myelogenous leukemia and the splice variant BCR-ABL1(35INS). AB - PURPOSE: In patients with chronic myelogenous leukemia (CML), point mutations in the BCR-ABL1 kinase domain are the most common cause of treatment failure with a tyrosine kinase inhibitor (TKI). It is not clear whether the splice variant BCR ABL1(35INS) is also associated with treatment failure. PATIENTS AND METHODS: We reviewed all CML patients who had BCR-ABL1 kinase mutation analysis performed between August 1, 2007, and January 15, 2014. Patients who had BCR-ABL1(35INS) detected had their medical records reviewed to determine response to TKI therapy. RESULTS: Two hundred and eighty four patients had kinase mutation testing performed; of these, 64 patients (23%) had BCR-ABL1(35INS) detected. Forty-five patients were in chronic phase (70%), 10 were in accelerated phase (16%), 6 were in blastic phase (9%), and 3 were in other settings (5%). Of the 34 chronic phase patients who began therapy with imatinib, 23 patients (68%) failed therapy: 8 patients (24%) had primary refractory disease, 11 patients (32%) progressed, and 4 patients (12%) had disease progression after dose interruption. In contrast to the patients with disease progression or lack of response, none of 23 patients who were responding to imatinib had BCR-ABL1(35INS) detected. DNA sequencing of commonly mutated spliceosomal genes SF3B1, U2AF1, SRSF2, ZRSR2, SFA31, PRPF408, U2A565, and SF1 did not reveal mutations in seven BCR-ABL1(35INS) -positive patients tested. CONCLUSIONS: The splice variant BCR-ABL1(35INS) is frequently found in patients who are resistant to imatinib. Mutations in the commonly mutated spliceosomal proteins do not contribute to this association. PMID- 27658273 TI - Sydenham on Hysteria. AB - This historical essay outlines early ideas and clinical accounts of hysteria. It reproduces verbatim parts of a remarkable text of Thomas Sydenham. This provides the most detailed description of hysterical symptoms, contemporary treatment and particularly Sydenham's opinions about the nature of the disorder. His portrayal is compared to later and modern concepts and classification. PMID- 27658274 TI - Harmful Emotional Responses that Patients and Physicians May Have When their Values Conflict. AB - One of the most difficult decisions a clinician may face is when, if ever, to decline what a patient wants, based on the clinician's own moral conscience. Regardless of what the clinician decides, the outcome may be deeply emotionally painful for both parties, and the pain may last. I will discuss this pain, how it occurs, and what we can do to try to reduce it before, during, and after a conflict arises. Approaches include explaining how we are like the patient or doctor, that no one is perfect, and that what we do is not who we are. PMID- 27658275 TI - Moral Agency, Moral Imagination, and Moral Community: Antidotes to Moral Distress. AB - Moral distress has been covered extensively in the nursing literature and increasingly in the literature of other health professions. Cases that cause nurses' moral distress that are mentioned most frequently are those concerned with prolonging the dying process. Given the standard of aggressive treatment that is typical in intensive care units (ICUs), much of the existing moral distress research focuses on the experiences of critical care nurses. However, moral distress does not automatically occur in all end-of-life circumstances, nor does every critical care nurse suffer its damaging effects. What are the practices of these nurses? What specifically do they do to navigate around or through the distressing situations? The nursing literature is lacking an answer to these questions. This article reports a study that used narrative analysis to explore the reported practices of experienced critical care nurses who are skilled at and comfortable working with families and physicians regarding the withdrawal of aggressive treatment. A major finding was that these nurses did not report experiencing the damaging effects of moral distress as described in the nursing literature. The verbal communication and stated practices relevant to this finding are organized under three major themes: (1) moral agency, (2) moral imagination, and (3) moral community. Further, a total of eight subthemes are identified. The practices that constitute these themes and subthemes are further detailed and discussed in this article. Understanding these practices can help mitigate critical care nurses' moral distress. PMID- 27658276 TI - Towards a New Narrative of Moral Distress: Realizing the Potential of Resilience. AB - Terri Traudt, Joan Liaschenko, and Cynthia Peden-McAlpine's study contributes to a much-needed reorientation in thinking about and working with the challenges of moral distress. In providing a vital example of nurses able to navigate morally distressing situations in positive and constructive ways, and offering an analysis of the component elements of these nurses' success, the study helps identify promising directions we might take in addressing the epidemic of moral distress. It also invites important questions, concerning the challenges faced by clinicians who do not who work in healthy "moral communities," who lack the ethical competencies, and who don't have the presumptive authority and recognition enjoyed by the seasoned clinicians studied here. We explore some of these questions, and suggest ways we might build on the insights of Traudt and colleagues' study. PMID- 27658277 TI - Report by the American Medical Association's Council on Ethical and Judicial Affairs on Physicians' Exercise of Conscience. AB - As practicing clinicians, physicians are expected to uphold the ethical norms of their profession, including fidelity to patients and respect for patients' self determination. At the same time, as individuals, physicians are moral agents in their own right and, like their patients, are informed by and committed to diverse cultural, religious, and philosophical traditions and beliefs. In some circumstances, the expectation that physicians will put patients' needs and preferences first may be in tension with the need to sustain the sense of moral integrity and continuity that grounds a physician's personal and professional life. This article examines the implications for patients, physicians, and the medical profession when tensions arise between a physician's professional commitments and his or her deeply held personal moral beliefs. It offers guidance on when a physician's professional commitments should outweigh personal beliefs as well as when physicians should have freedom to act according to the dictates of conscience while still protecting patients' interests. PMID- 27658278 TI - Accommodating Conscientious Objection in Medicine-Private Ideological Convictions Must Not Trump Professional Obligations. AB - The opinion of the American Medical Association (AMA) Council on Ethical and Judicial Affairs (CEJA) on the accommodation of conscientious objectors among medical doctors aims to balance fairly patients' rights of access to care and accommodating doctors' deeply held personal beliefs. Like similar documents, it fails. Patients will not find it persuasive, and neither should they. The lines drawn aim at a reasonable compromise between positions that are not amenable to compromise. They are also largely arbitrary. This article explains why that is the case. The view that conscientious objection accommodation has no place in modern medicine is defended. PMID- 27658279 TI - Professional Ethics, Personal Conscience, and Public Expectations. AB - Examining to what extent physicians are, or ought to be, defined by the profession when giving advice to patients, this commentary seeks to offer a better understanding of the potential conflicts that the American Medical Association's (AMA's) "Opinion 1.1.7, Physician Exercise of Conscience," addresses. This commentary conceptualizes the professions as knowledge communities, and situates the physician-patient relationship within this larger conceptual framework. So doing, it sheds light on how and when specialized knowledge is operationalized in professional advice-giving. Physicians communicate the knowledge community's insights to the patient. Thus, departures from professional knowledge as a matter of the professional's personal conscience are appropriately circumscribed by the knowledge community. PMID- 27658280 TI - Who Judges Harm? AB - The American Medical Association's (AMA's) "Opinion 1.1.7, Physician Exercise of Conscience" attempts to help physicians strike a reasonable balance between their own conscientious beliefs and their patients' medical interests in an effort to minimize harms to both. However, some ambiguity still remains as to whether the severity of harms experienced by physicians and patients is to be assessed externally (by policy makers or by a professional body like the AMA), or internally by the subjects of those harms. Conflicts between conscientious physicians' self-assessments of the moral harm associated with various actions and the AMA's external assessments of such harms are likely to lead to challenges in the implementation of some provisions of its opinion. This commentary argues, however, that provisions (b) and (e) of the opinion, which describe the information physicians should provide about their own scope of practice and about the existence of controversial procedures, are less likely to conflict with physicians' subjective assessments of moral harm, and therefore will face fewer challenges in implementation. PMID- 27658281 TI - Action Steps and Solutions for Physicians' Exercise of Conscience. AB - Conscience can influence physicians' interactions with patients in myriad ways and, by extension, can influence the interactions and internal dynamics of a health care team. The AMA's opinion around physicians' exercise of conscience appropriately balance the obligations physicians have to their patients and profession, and the rights of physicians as moral agents to exercise their conscience. While the opinion is an effective starting point, further guidance is necessary to clarify the process by which physicians should identify, manage, and, if necessary, report their conscientious refusals to patients, supervisors, or colleagues. In addition to laying out a proposed process for identifying and managing issues of conscience, this article will use relevant and timely examples to help clarify how a physician could apply this process in an instance of conscientious refusal. PMID- 27658282 TI - Conscientious Objection: Widening the Temporal and Organizational Horizons. AB - Conscience can influence physicians' interactions with patients in myriad ways and, by extension, can influence the interactions and internal dynamics of a health care team. The AMA's opinion around physicians' exercise of conscience appropriately balance the obligations physicians have to their patients and profession, and the rights of physicians as moral agents to exercise their conscience. While the opinion is an effective starting point, further guidance is necessary to clarify the process by which physicians should identify, manage, and, if necessary, report their conscientious refusals to patients, supervisors, or colleagues. In addition to laying out a proposed process for identifying and managing issues of conscience, this article will use relevant and timely examples to help clarify how a physician could apply this process in an instance of conscientious refusal. PMID- 27658283 TI - Thinking about Conscience. AB - The path to consensus about physicians' exercise of conscience was not linear. It looped back on itself as new insights illuminated earlier deliberations and in turn led to further insights. In particular, coming to agreement about physicians' responsibility in regard to referral charted a route through many course corrections. PMID- 27658284 TI - Legal Briefing: Stopping Nonbeneficial Life-Sustaining Treatment without Consent. AB - In the United States, authoritative legal guidance remains sparse on whether or when clinicians may stop life-sustaining treatment without consent. Fortunately, several significant legislative and judicial developments over the past two years offer some clarity. We group these legal developments into the following seven categories: 1. Lawsuits for Damages 2. Amendments to the Texas Advance Directives Act 3. Constitutional Attack on TADA 4. Legislation Prohibiting Clinicians 5. Legislation Authorizing Clinicians 6. Cases from Canada 7. Cases from the United Kingdom. PMID- 27658285 TI - Diagnostic and Therapeutic Challenges. PMID- 27658286 TI - CHOROIDAL AND RETINAL ATROPHY OF BIETTI CRYSTALLINE DYSTROPHY PATIENTS WITH CYP4V2 MUTATIONS COMPARED TO RETINITIS PIGMENTOSA PATIENTS WITH EYS MUTATIONS. AB - PURPOSE: To compare atrophy of the choroid and retina between Bietti crystalline dystrophy (BCD) patients and EYS-related retinitis pigmentosa (RP) patients with a similar degree of central visual field defects, age, and axial length (AL). METHODS: Nine eyes of nine BCD patients with CYP4V2 mutations (BCD group) were examined. Moreover, we selected 10 eyes of 10 RP patients with EYS mutations matched for age, axial length, and mean deviation (measured with the 10-2 SITA standard program; EYS-RP group), and 10 eyes of 10 normal volunteers matched for age and axial length (control group). Macular thicknesses of the choroid and retina were measured via swept-source optical coherence tomography. RESULTS: The macular choroid was significantly thinner in the BCD group than in the EYS-RP and control groups, although the thickness did not significantly differ between the EYS-RP and control groups. The macular retina was significantly thinner in the BCD and EYS-RP groups than in the control group, although the thickness did not significantly differ between the BCD and EYS-RP groups at most sites. CONCLUSION: Bietti crystalline dystrophy patients with CYP4V2 mutations showed more severe macular choroid atrophy as compared to EYS-related RP patients. These different damage patterns suggest differences in choroidal expression between CYP4V2 and EYS. PMID- 27658288 TI - A Comparison of the Effectiveness of Sodium Stibogluconate Monotherapy to Sodium Stibogluconate and Paromomycin Combination for the Treatment of Severe Post Kala Azar Dermal Leishmaniasis in South Sudan - A Retrospective Cohort Study. AB - BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a common dermatological complication following successful treatment of Visceral Leishmaniasis (VL) caused by Leishmania donovani. PKDL presents as macular, papular, nodular or mixed skin rash on sun-exposed body parts. Patients are not ill unless there are complications due to mucosal involvement or ulceration. As PKDL in East Africa is typically self-healing, and treatment is long and with significant adverse events, only severe and complicated cases are treated. Studies to determine optimal treatment of PKDL are rare and based on small cohorts. Since 1989, Medecins Sans Frontieres is treating severe PKDL within VL treatment programmes in South Sudan. Treatment was initially with sodium stibogluconate (SSG) monotherapy and since 2002 with a combination of SSG and paromomycin (PM). SSG monotherapy (20 mg/kg/day for a minimum of 30 days) was provided in primary health units, and the combination of PM (15 mg sulphate/kg/day for 17 days) plus SSG (30 mg/kg/day for a minimum of 17 days) was provided in secondary health facilities. METHODOLOGY/PRINCIPAL FINDINGS: By retrospective analysis of routinely collected programme data we compared the effectiveness (outcome and treatment duration) of both regimens. Between 2002 and 2008, 422 patients with severe PKDL were treated; 343 received SSG and 79 SSG/PM combination. The cure rate was significantly better with combination treatment when compared to monotherapy (97% vs. 90%; odds ratio [OR], 7.6; p = 0.02), treatment duration was shorter (mean 34 days vs. 42 days; p = 0.005), and defaulter rate was lower (3% vs. 9%; OR, 0.3; p = 0.03). There was no significant difference in death rate (0% vs. 1%; p = 0.5). CONCLUSIONS/SIGNIFICANCE: We found that SSG/PM combination therapy resulted in more favourable outcomes than SSG monotherapy. An additional advantage is the lower cost of the combination therapy, due to the shorter treatment duration. A combination of SSG and PM is therefore a suitable option for the treatment of PKDL in East Africa. PMID- 27658289 TI - The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia. AB - Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction. PMID- 27658290 TI - Postpartum Vascular Dysfunction in the Reduced Uteroplacental Perfusion Model of Preeclampsia. AB - Preeclampsia is a disorder affecting 2-8% of all pregnancies, characterized by gestational hypertension (>= 140/90 mmHg) and proteinuria (>=300 mg over 24 hours) diagnosed following the 20th week of pregnancy, and for which there is currently no available treatment. While the precise cause of preeclampsia is unknown, placental ischemia/hypoxia resulting from abnormal trophoblast invasion and maternal endothelial dysfunction are central characteristics. Preeclampsia is a major cause of both maternal and fetal morbidity and mortality in the perinatal period. In addition, women who have experienced preeclampsia are more likely to suffer cardiovascular disease later in life. The cause of this elevation in cardiovascular risk postpartum, however, is unknown. We hypothesize that there may be lasting vascular dysfunction following exposure to reduced uteroplacental perfusion during pregnancy that may contribute to increased cardiovascular risk postpartum. Using the rat reduced utero-placental perfusion pressure (RUPP) model of preeclampsia, blood pressure was assessed in dams at gestational day 20, one and three months postpartum. Mesenteric artery and aortic function were assessed using wire myography. We demonstrated hypertension and increased mesenteric artery responses to phenylephrine at gestational day 20, with the latter due to a decreased contribution of nitric oxide without any change in methylcholine induced relaxation. At one month postpartum, we demonstrated a small but significant vasoconstrictive phenotype that was due to an underlying loss of basal nitric oxide contribution. At three months postpartum, endothelium dependent relaxation of the aorta demonstrated sensitivity to oxLDL and mesenteric arteries demonstrated decreased nitric oxide bioavailability with impaired methylcholine-induced relaxation; indicative of an early development of endothelial dysfunction. In summary, we have demonstrated impaired vascular function following exposure to a RUPP pregnancy that continued into the postpartum period; suggesting that a pregnancy complicated by preeclampsia may predispose women to later life cardiovascular disease via ongoing vascular dysfunction. PMID- 27658291 TI - Evaluation of Psoriasis Genetic Risk Based on Five Susceptibility Markers in a Population from Northern Poland. AB - Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (HLA-C, ERAP1, ZAP70) and in the skin barrier function (LCE3, CSTA) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8*10-7). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9*10-14). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative HLA-C*06 allele. PMID- 27658292 TI - Cerebral Cortical Thickness in Chronic Pain Due to Knee Osteoarthritis: The Effect of Pain Duration and Pain Sensitization. AB - OBJECTIVE: This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. METHODS: Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1+/- 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7+/- 7.4, 17 females). RESULTS: Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. CONCLUSION: With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role. PMID- 27658295 TI - Correction: Clinical Impact of MALDI-TOF MS Identification and Rapid Susceptibility Testing on Adequate Antimicrobial Treatment in Sepsis with Positive Blood Cultures. AB - [This corrects the article DOI: 10.1371/journal.pone.0156299.]. PMID- 27658294 TI - Alternative Splicing of Toll-Like Receptor 9 Transcript in Teleost Fish Grouper Is Regulated by NF-kappaB Signaling via Phosphorylation of the C-Terminal Domain of the RPB1 Subunit of RNA Polymerase II. AB - Similar to its mammalian counterparts, teleost Toll-like receptor 9 (TLR9) recognizes unmethylated CpG DNA presented in the genome of bacteria or DNA viruses and initiates signaling pathway(s) for immune responses. We have previously shown that the TLR9 pathway in grouper, an economically important teleost, can be debilitated by an inhibitory gTLR9B isoform, whose production is mediated by RNA alternative splicing. However, how does grouper TLR9 (gTLR9) signaling impinge on the RNA splicing machinery to produce gTlr9B is unknown. Here we show that the gTlr9 alternative splicing is regulated through ligand induced phosphorylation of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II). We first observed that ligand-activated NF- kappaB pathway biased the production of the gTlr9B isoform. Because NF- kappaB is known to recruit p-TEFb kinase, which phosphorylates the Pol II CTD at Ser2 residues, we examined p-TEFb's role in alternative splicing. We found that promoting p-TEFb kinase activity significantly favored the production of the gTlr9B isoform, whereas inhibiting p-TEFb yielded an opposite result. We further showed that p TEFb-mediated production of the gTlr9B isoform down-regulates its own immune responses, suggesting a self-limiting mechanism. Taken together, our data indicate a feedback mechanism of the gTLR9 signaling pathway to regulate the alternative splicing machinery, which in turn produces an inhibitor to the pathway. PMID- 27658293 TI - Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract. AB - Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels. PMID- 27658296 TI - Beyond Zipf's Law: The Lavalette Rank Function and Its Properties. AB - Although Zipf's law is widespread in natural and social data, one often encounters situations where one or both ends of the ranked data deviate from the power-law function. Previously we proposed the Beta rank function to improve the fitting of data which does not follow a perfect Zipf's law. Here we show that when the two parameters in the Beta rank function have the same value, the Lavalette rank function, the probability density function can be derived analytically. We also show both computationally and analytically that Lavalette distribution is approximately equal, though not identical, to the lognormal distribution. We illustrate the utility of Lavalette rank function in several datasets. We also address three analysis issues on the statistical testing of Lavalette fitting function, comparison between Zipf's law and lognormal distribution through Lavalette function, and comparison between lognormal distribution and Lavalette distribution. PMID- 27658298 TI - Correction: Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis. AB - [This corrects the article DOI: 10.1371/journal.pone.0160350.]. PMID- 27658297 TI - Fully-Automated MUMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome. AB - We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from MUMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings. PMID- 27658300 TI - MiR-375 Is Epigenetically Downregulated by HPV-16 E6 Mediated DNMT1 Upregulation and Modulates EMT of Cervical Cancer Cells by Suppressing lncRNA MALAT1. AB - Epigenetic modulation is an important mechanism of miRNA dysregulation in cervical cancer. In this study, we firstly studied how this mechanism contributes to miR-375 downregulation in cervical cancer cells. Then, we further studied the association between miR-375 and MALAT1 (metastasis associated lung adenocarcinoma transcript 1) in epithelial mesenchymal transition (EMT) of the cancer cells. HPV 16 positive SiHa and CaSki cells were used as in vitro model. Our data showed that HPV-16 E6 positively modulated DNMT1 expression in both SiHa and CaSki cells. Knockdown of DNMT1 partly restored miR-375 levels in the cells. The following methylation-specific PCR (MSP) assay and qRT-PCR analysis showed that methylation was common in the promoter region of miR-375 in both SiHa and CaSki cells and demethylation partly restored miR-375 levels in the cells. Therefore, we infer that miR-375 is downregulated partly due to promoter hypermethylation mediated by DNMT1 in HPV-16 positive cervical cancer cells. Our bioinformatics analysis showed that MALAT1 has three putative binding sites with miR-375 and the following dual luciferase assay confirmed two of them. QRT-PCR analysis showed that miR-375 overexpression significantly reduced MALAT1 expression, while MALAT1 overexpression reversely suppressed miR-375 levels. Therefore, we infer that there is a reciprocal regulation between miR-375 and MALAT1 in the cells. In SiHa cells, miR-375 overexpression or MALAT1 siRNA partly restored E-cadherin expression, significantly reduced N-cadherin and also reduced invasion capacity of SiHa cells. Therefore, these results suggest that miR-375 and MALAT1 form a functional axis modulating EMT in cervical cancer. PMID- 27658299 TI - Influence of Proximal, Distal, and Vestibular Frames of Reference in Object-Place Paired Associate Learning in the Rat. AB - Object-place paired associate learning has been used to test hypotheses regarding the neurobiological basis of memory in rodents. Much of this work has focused on the role of limbic and hippocampal-parahippocampal regions, as well as the use of spatial information derived from allothetic visual stimuli to determine location in an environment. It has been suggested that idiothetic self-motion (vestibular) signals and internal representations of directional orientation might play an important role in disambiguating between spatial locations when forming object place associations, but this hypothesis has not been explicitly tested. In the present study, we investigated the relationship between allothetic (i.e., distal and proximal cues) and vestibular stimuli on performance of an object-place paired-associate task. The paired-associate task was composed of learning to discriminate between an identical pair of objects presented in 180 degrees opposite arms of a radial arm maze. Thus, animals were required to select a particular object on the basis of spatial location (i.e., maze arm). After the animals acquired the object-place rule, a series of probe tests determined that rats utilize self-generated vestibular cues to discriminate between the two maze arms. Further, when available, animals showed a strong preference for local proximal cues associated with the maze. Together, the work presented here supports the establishment of an object-place task that requires both idiothetic and allothetic stimulus sources to guide choice behavior, and which can be used to further investigate the dynamic interactions between neural systems involved in pairing sensory information with spatial locations. PMID- 27658302 TI - Differential Communications between Fungi and Host Plants Revealed by Secretome Analysis of Phylogenetically Related Endophytic and Pathogenic Fungi. AB - During infection, both phytopathogenic and endophytic fungi form intimate contact with living plant cells, and need to resist or disable host defences and modify host metabolism to adapt to their host. Fungi can achieve these changes by secreting proteins and enzymes. A comprehensive comparison of the secretomes of both endophytic and pathogenic fungi can improve our understanding of the interactions between plants and fungi. Although Magnaporthe oryzae, Gaeumannomyces graminis, and M. poae are economically important fungal pathogens, and the related species Harpophora oryzae is an endophyte, they evolved from a common pathogenic ancestor. We used a pipeline analysis to predict the H. oryzae, M. oryzae, G. graminis, and M. poae secretomes and identified 1142, 1370, 1001, and 974 proteins, respectively. Orthologue gene analyses demonstrated that the M. oryzae secretome evolved more rapidly than those of the other three related species, resulting in many species-specific secreted protein-encoding genes, such as avirulence genes. Functional analyses highlighted the abundance of proteins involved in the breakdown of host plant cell walls and oxidation-reduction processes. We identified three novel motifs in the H. and M. oryzae secretomes, which may play key roles in the interaction between rice and H. oryzae. Furthermore, we found that expression of the H. oryzae secretome involved in plant cell wall degradation was downregulated, but the M. oryzae secretome was upregulated with many more upregulated genes involved in oxidation-reduction processes. The divergent in planta expression patterns of the H. and M. oryzae secretomes reveal differences that are associated with mutualistic and pathogenic interactions, respectively. PMID- 27658301 TI - The Feedback-Related Negativity and the P300 Brain Potential Are Sensitive to Price Expectation Violations in a Virtual Shopping Task. AB - A large body of evidence shows that buying behaviour is strongly determined by consumers' price expectations and the extent to which real prices violate these expectations. Despite the importance of this phenomenon, little is known regarding its neural mechanisms. Here we show that two patterns of electrical brain activity known to index prediction errors-the Feedback-Related Negativity (FRN) and the feedback-related P300 -were sensitive to price offers that were cheaper than participants' expectations. In addition, we also found that FRN amplitude time-locked to price offers predicted whether a product would be subsequently purchased or not, and further analyses suggest that this result was driven by the sensitivity of the FRN to positive price expectation violations. This finding strongly suggests that ensembles of neurons coding positive prediction errors play a critical role in real-life consumer behaviour. Further, these findings indicate that theoretical models based on the notion of prediction error, such as the Reinforcement Learning Theory, can provide a neurobiologically grounded account of consumer behavior. PMID- 27658303 TI - G Protein-Coupled Receptor 43 Modulates Neutrophil Recruitment during Acute Inflammation. AB - Fermentation of dietary fibre in the gut yields large amounts of short chain fatty acids (SCFAs). SCFAs can impart biological responses in cells through their engagement of 'metabolite-sensing' G protein-coupled receptors (GPCRs). One of the main SCFA receptors, GPR43, is highly expressed by neutrophils, which suggests that the actions of GPR43 and dietary fibre intake may affect neutrophil recruitment during inflammatory responses in vivo. Using intravital imaging of the small intestine, we found greater intravascular neutrophil rolling and adhesion in Gpr43-/-mice in response to LPS at 1 h. After 4 h of LPS challenge, the intravascular rolling velocity of GPR43-deficient neutrophils was reduced significantly and increased numbers of neutrophils were found in the lamina propria of Gpr43-/-mice. Additionally, GPR43-deficient leukocytes demonstrated exacerbated migration into the peritoneal cavity following fMLP challenge. The fMLP-induced neutrophil migration was significantly suppressed in wildtype mice that were treated with acetate, but not in Gpr43-/-mice, strongly suggesting a role for SCFAs in modulating neutrophil migration via GPR43. Indeed, neutrophils of no fibre-fed wildtype mice exhibited elevated migratory behaviour compared to normal chow-fed wildtype mice. Interestingly, this elevated migration could also be reproduced through simple transfer of a no fibre microbiota into germ-free mice, suggesting that the composition and function of microbiota stemming from a no fibre diet mediated the changes in neutrophil migration. Therefore, GPR43 and a microbiota composition that allows for SCFA production function to modulate neutrophil recruitment during inflammatory responses. PMID- 27658304 TI - Time Course Analysis of Skeletal Muscle Pathology of GDE5 Transgenic Mouse. AB - Glycerophosphodiesterase 5 (GDE5) selectively hydrolyses glycerophosphocholine to choline and is highly expressed in type II fiber-rich skeletal muscles. We have previously generated that a truncated mutant of GDE5 (GDE5dC471) that lacks phosphodiesterase activity and shown that transgenic mice overexpressing GDE5dC471 in skeletal muscles show less skeletal muscle mass than control mice. However, the molecular mechanism and pathophysiological features underlying decreased skeletal muscle mass in GDE5dC471 mice remain unclear. In this study, we characterized the skeletal muscle disorder throughout development and investigated the primary cause of muscle atrophy. While type I fiber-rich soleus muscle mass was not altered in GDE5dC471 mice, type II fiber-rich muscle mass was reduced in 8-week-old GDE5dC471 mice. Type II fiber-rich muscle mass continued to decrease irreversibly in 1-year-old transgenic mice with an increase in apoptotic cell. Adipose tissue weight and blood triglyceride levels in 8-week-old and 1 year-old transgenic mice were higher than those in control mice. This study also demonstrated compensatory mRNA expression of neuromuscular junction (NMJ) components, including nicotinic acetylcholine receptors (alpha1, gamma, and epsilon subunits) and acetylcholinesterase in type II fiber-rich quadriceps muscles in GDE5dC471 mice. However, we did not observe morphological changes in NMJs associated with skeletal muscle atrophy in GDE5dC471 mice. We also found that HSP70 protein levels are significantly increased in the skeletal muscles of 2-week-old GDE5dC471 mice and in mouse myoblastic C2C12 cells overexpressing GDE5dC471. These findings suggest that GDE5dC471 mouse is a novel model of early onset irreversible type II fiber-rich myopathy associated with cellular stress. PMID- 27658305 TI - The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies. AB - Curcumin (CUR) is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 MUM on epimastigotes). Demethoxycurcumin (DMC) was equipotent to CUR (IC50 11.07 MUM), but bisdemethoxycurcumin (BDMC) was less active (IC50 45.33 MUM) and cyclocurcumin (CC) was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel's mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations. PMID- 27658307 TI - Correction: Association of Empirically Derived Dietary Patterns with Cardiovascular Risk Factors: A Comparison of PCA and RRR Methods. AB - [This corrects the article DOI: 10.1371/journal.pone.0161298.]. PMID- 27658306 TI - Elevated Platelet to Lymphocyte Ratio Is Associated with Poor Survival Outcomes in Patients with Colorectal Cancer. AB - Platelet to lymphocyte ratio (PLR) is a parameter reflecting inflammatory responses in patients with cancer. Several studies have investigated the prognostic value of PLR in patients with colorectal cancer (CRC); however, the results are controversial. Thus, we carried out a meta-analysis to evaluate the association between PLR and CRC prognostication. Relevant articles were retrieved through PubMed, Embase, and Web of Science, and pooled hazard ratio (HR) and 95% confidence interval (CI) were computed by using STATA V.12.0. Both the random effects model and fixed-effects model were utilized. A total of 13 studies (14 cohorts) with 8,601 patients were included in the meta-analysis. Pooled HRs and 95% CIs demonstrated that increased PLR predicted poor overall survival (OS) (HR = 1.81, 95%CI:1.42-2.31, p<0.001; I2 = 65%, Ph = 0.002), disease-free survival (DFS) (HR = 1.84, 95%CI:1.22-2.76, p = 0.003; I2 = 78.3%, Ph<0.001) and recurrence-free survival (RFS) (HR = 1.84, 95%CI:1.41-2.41, p<0.001; I2 = 0, Ph = 0.686), although this was not the case for cancer-specific survival (CSS) (HR = 1.75, 95%CI:0.59-5.17, p = 0.309; I2 = 66.2%, Ph = 0.085) or time to recurrence (TTR) (HR = 1.21 95%CI:0.62-2.36, p = 0.573;I2 = 58.4%, Ph = 0.121). Subgroup analysis showed that PLR enhanced the prognostic value for OS in Caucasian patients, in small sample studies and for metastatic disease; however, this was not the case with rectal cancer. Furthermore, elevated PLR predicted reduced DFS in Caucasians and not in Asians. In conclusion, our meta-analysis showed that high PLR was a significant biomarker for poor OS, DFS, and RFS in patients with CRC; however, it had no association with CSS or TTR. PMID- 27658308 TI - Growth in Total Height and Its Components and Cardiometabolic Health in Childhood. AB - BACKGROUND: Short stature or short legs is associated with cardiometabolic disease. Few studies have addressed this issue in children, incorporated repeated measures, or studied modern cohorts. METHODS: We examined if change in total height, leg length and trunk length between two time points from early (median: 3.2 years) to mid-childhood (median: 7.7 years), with and without adjustment for concurrent change in adiposity (subscapular plus triceps skinfold thickness), was associated with mid-childhood cardiometabolic risk in 315 boys and 295 girls from Project Viva. The main outcome was a cardiometabolic risk score based on sex specific internal z-scores for systolic blood pressure, waist circumference, homeostatic model assessment of insulin resistance, triglycerides and high density lipoprotein-cholesterol. RESULTS: Mean (SD) total height was 97.9 (4.5) cm in boys and 97.1 (4.7) cm in girls in early childhood and 129.1 (7.2) cm in boys and 128.3 (7.9) cm in girls in mid-childhood. Trunk length constituted about half of total height. In linear regression models adjusted for parental anthropometry and socio-demographics, faster growth in total height, leg length and particularly trunk length, were associated with higher cardiometabolic risk in mid-childhood. Per 1 cm annual increase in trunk length, the cardiometabolic risk score was 0.23 z-score (95% confidence interval [CI] 0.08, 0.39) higher among boys and 0.47 z-score (95% CI 0.33, 0.60) higher among girls. Estimates were attenuated after adjusting for adiposity (boys: 0.03 z-score, 95% CI -0.11, 0.18; girls: 0.32 z-score, 95% CI 0.19, 0.45). CONCLUSION: Rapid linear growth, particularly in trunk length, was associated with higher cardiometabolic risk in childhood, which was explained by relationships of linear growth with adiposity in boys, but only partly in girls. PMID- 27658310 TI - Effects of Leading Edge Defect on the Aerodynamic and Flow Characteristics of an S809 Airfoil. AB - BACKGROUND: Unexpected performance degradation occurs in wind turbine blades due to leading edge defect when suffering from continuous impacts with rain drops, hails, insects, or solid particles during its operation life. To assess this issue, this paper numerically investigates the steady and dynamic stall characteristics of an S809 airfoil with various leading edge defects. More leading edge defect sizes and much closer to practical parameters are investigated in the paper. METHODOLOGY: Numerical computation is conducted using the SST k-omega turbulence model, and the method has been validated by comparison with existed published data. In order to ensure the calculation convergence, the residuals for the continuity equation are set to be less than 10-7 and 10-6 in steady state and dynamic stall cases. The simulations are conducted with the software ANSYS Fluent 13.0. RESULTS: It is found that the characteristics of aerodynamic coefficients and flow fields are sensitive to leading edge defect both in steady and dynamic conditions. For airfoils with the defect thickness of 6%tc, leading edge defect has a relative small influence on the aerodynamics of S809 airfoil. For other investigated defect thicknesses, leading edge defect has much greater influence on the flow field structures, pressure coefficients and aerodynamic characteristics of airfoil at relative small defect lengths. For example, the lift coefficients decrease and drag coefficients increase sharply after the appearance of leading edge defect. However, the aerodynamic characteristics could reach a constant value when the defect length is large enough. The flow field, pressure coefficient distribution and aerodynamic coefficients do not change a lot when the defect lengths reach to 0.5%c,1%c, 2%c and 3%c with defect thicknesses of 6%tc, 12%tc,18%tc and 25%tc, respectively. In addition, the results also show that the critical defect length/thickness ratio is 0.5, beyond which the aerodynamic characteristics nearly remain unchanged. In dynamic stall, leading edge defect imposes a greater influence on the aerodynamic characteristics of airfoil than steady conditions. By increasing in defect length, it is found that the separated area becomes more intense and moves forward along the suction surface. CONCLUSIONS: Leading edge defect has significant influence on the aerodynamic and flow characteristics of the airfoil, which will reach a stable status with enough large defect size. The leading edge separation bubble, circulation in the defect cavity and intense tailing edge vortex are the main features of flow around defective airfoils. PMID- 27658311 TI - [Vorwort]. PMID- 27658309 TI - Heterogeneous Aging Effects on Functional Connectivity in Different Cortical Regions: A Resting-State Functional MRI Study Using Functional Data Analysis. AB - Brain aging is a complex and heterogeneous process characterized by the selective loss and preservation of brain functions. This study examines the normal aging effects on the cerebral cortex by characterizing changes in functional connectivity using resting-state fMRI data. Previous resting-state fMRI studies on normal aging have examined specific networks of the brain, whereas few studies have examined cortical-cortical connectivities across the entire brain. To characterize the effects of normal aging on the cerebral cortex, we proposed the Pearson functional product-moment correlation coefficient for measuring functional connectivity, which has advantages over the traditional correlation coefficient. The distinct patterns of changes in functional connectivity within and among the four cerebral lobes clarified the effects of normal aging on cortical function. Besides, the advantages of the proposed approach over other methods considered were demonstrated through simulation comparisons. The results showed heterogeneous changes in functional connectivity in normal aging. Specifically, the elderly group exhibited enhanced inter-lobe connectivity between the frontal lobe and the other lobes. Inter-lobe connectivity decreased between the temporal and parietal lobes. The results support the frontal aging hypothesis proposed in behavioral and structural MRI studies. In conclusion, functional correlation analysis enables differentiation of changes in functional connectivities and characterizes the heterogeneous aging effects in different cortical regions. PMID- 27658312 TI - Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology. AB - BACKGROUND: Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS. MATERIALS AND METHODS: The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model. RESULTS: In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 +/- 3.5%, the lipid volume fraction was 9.9 +/- 4.7%, and the bile volume fraction was 8.2 +/- 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively. CONCLUSION: This study shows that it is possible to manage DRS measurements through the liver capsule and that surface DRS measurements are representative of the whole liver. The results are consistent with data published earlier on the combination of liver chromophores. The results encourage us to proceed with in vivo measurements for further quantification of the liver's composition and assessment of parenchymal damage such as steatosis and fibrosis grade. PMID- 27658313 TI - Medicare and Medicaid Programs; Emergency Preparedness Requirements for Medicare and Medicaid Participating Providers and Suppliers. Final rule. AB - This final rule establishes national emergency preparedness requirements for Medicare- and Medicaid-participating providers and suppliers to plan adequately for both natural and man-made disasters, and coordinate with federal, state, tribal, regional, and local emergency preparedness systems. It will also assist providers and suppliers to adequately prepare to meet the needs of patients, residents, clients, and participants during disasters and emergency situations. Despite some variations, our regulations will provide consistent emergency preparedness requirements, enhance patient safety during emergencies for persons served by Medicare- and Medicaid-participating facilities, and establish a more coordinated and defined response to natural and man-made disasters. PMID- 27658314 TI - Medical Devices; General and Plastic Surgery Devices; Classification of the Magnetic Surgical Instrument System. Final order. AB - The Food and Drug Administration (FDA) is classifying the Magnetic Surgical Instrument System into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the magnetic surgical instrument system's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 27658315 TI - Clinical Trials Registration and Results Information Submission. Final rule. AB - This final rule details the requirements for submitting registration and summary results information, including adverse event information, for specified clinical trials of drug products (including biological products) and device products and for pediatric postmarket surveillances of a device product to ClinicalTrials.gov, the clinical trial registry and results data bank operated by the National Library of Medicine (NLM) of the National Institutes of Health (NIH). This rule provides for the expanded registry and results data bank specified in Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) to help patients find trials for which they might be eligible, enhance the design of clinical trials and prevent duplication of unsuccessful or unsafe trials, improve the evidence base that informs clinical care, increase the efficiency of drug and device development processes, improve clinical research practice, and build public trust in clinical research. The requirements apply to the responsible party (meaning the sponsor or designated principal investigator) for certain clinical trials of drug products (including biological products) and device products that are regulated by the Food and Drug Administration (FDA) and for pediatric postmarket surveillances of a device product that are ordered by FDA. PMID- 27658316 TI - Medical Devices; Ophthalmic Devices; Classification of Strabismus Detection Device. Final order. AB - The Food and Drug Administration (FDA) is classifying the strabismus detection device into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the strabismus detection device's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 27658318 TI - Rab11 and phosphoinositides: A synergy of signal transducers in the control of vesicular trafficking. AB - Rab11 and phosphoinositides are signal transducers able to direct the delivery of membrane components to the cell surface. Rab11 is a small GTPase that, by cycling from an active to an inactive state, controls key events of vesicular transport, while phosphoinositides are major determinants of membrane identity, modulating compartmentalized small GTPase function. By sharing common effectors, these two signal transducers synergistically direct vesicular traffic to specific intracellular membranes. This review focuses on the latest advances regarding the mechanisms that ensure the compartmentalized regulation of Rab11 function through its interaction with phosphoinositides. PMID- 27658320 TI - Development of a novel physico-chemically and microbiologically stable oral solution of flecainide for pediatrics. AB - There is as yet no commercialized preparation for oral administration of flecainide acetate (FA) to children. In such cases, manipulation of commercial tablets is the usual practice in pharmacy services of hospitals and compounding pharmacies, to provide a suitable dosage form for this vulnerable pediatric population group. In this study, we have formulated FA as an oral solution, as an alternative to the suspension elaborated from commercial tablets. Due to this sensitivity of young patients, we have used the pure active pharmaceutical ingredient (API) and the lowest permitted levels of pediatric excipients. Despite being a highly soluble API, only one of the formulations appears as a transparent solution due to complete FA solubilization. The proposed formulation is physico chemically and microbiologically stable and the mass and dose uniformity is appropriate for 30 days' storage at 25 degrees C. PMID- 27658319 TI - Nitric oxide synthase in plants: Where do we stand? AB - Over the past twenty years, nitric oxide (NO) has emerged as an important player in various plant physiological processes. Although many advances in the understanding of NO functions have been made, the question of how NO is produced in plants is still challenging. It is now generally accepted that the endogenous production of NO is mainly accomplished through the reduction of nitrite via both enzymatic and non-enzymatic mechanisms which remain to be fully characterized. Furthermore, experimental arguments in favour of the existence of plant nitric oxide synthase (NOS)-like enzymes have been reported. However, recent investigations revealed that land plants do not possess animal NOS-like enzymes while few algal species do. Phylogenetic and structural analyses reveals interesting features specific to algal NOS-like proteins. PMID- 27658321 TI - The new era of postgraduate certified general practice training in Japan. AB - This paper describes the background to, and the recent evolution of general practice as a recognised medical specialism in Japan (2015), and the evolution of a system of training to support this development. We, the general practitioners (GPs) in Japan have not been recognised as one body of medical specialists and have been training in our own way. A new certified training system will commence in 2018, authorised by a new third organisation, the Japanese Medical Specialty Board. An effective educational system has been developed for medical graduates that have a career intention in general practice that is distinct from other basic medical fields, but collaborates with them. A challenge exists to provide clarity to the Japanese population about what the specialty of general practice is, and what professionals in general practice can do for them. Japan currently has approximately 500 certified GPs and it is unclear at present what numbers will eventually be required. This paper reviews some of the challenges facing the development of general practice from the perspective of the Japan Primary Care Association. PMID- 27658323 TI - RIFM fragrance ingredient safety assessment, 2-ethyl-1-butanol, CAS Registry Number 97-95-0. AB - The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog 2-ethylhexanol (CAS # 104-76-7) show that this material is not genotoxic. Data from the suitable read across analog isopropyl alcohol (CAS # 67-63-0) show that this material does not have skin sensitization potential. The local respiratory toxicity endpoint was completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (1.4 mg/day). The repeated dose toxicity endpoint was completed using 2 ethylhexanol (CAS # 104-76-7) and 1-heptanol, 2-propyl (CAS # 10042-59-8) as suitable read across analogs, which provided a MOE > 100. The developmental and reproductive toxicity endpoint was completed using 2-ethyl-hexanol (CAS # 104-76 7) and isobutyl alcohol (CAS # 78-83-1) as suitable read across analogs, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework. PMID- 27658324 TI - Oxidative stress in rat brain but not in liver following oral administration of a low dose of nanoparticulate silver. AB - While it is known that silver nanoparticles (AgNPs) can enter the brain, our knowledge of AgNP-induced neurotoxicity remains incomplete. We investigated the ability of 10 nm citrate-stabilized AgNPs to generate oxidative stress in brain and liver of adult male Wistar rats after repeated oral exposure for 14 days, using a low dose of 0.2 mg/kg b.w. as compared with the same dose of ionic silver (silver citrate). In AgNP-exposed animals, the level of reactive oxygen species (ROS), lipid peroxidation (MDA) and glutathione peroxidase (GPx) activity were found to be significantly higher in brain relative to the control group receiving saline. Administration of ionic silver (silver citrate) increased ROS and MDA levels in both tissues. Activities of GPx in brain so as superoxide dismutase (SOD) and catalase (CAT) in liver of exposed animals were also elevated. Besides, AgNPs and silver ions were both found to cause statistically significant decrease in the reduced-to-oxidized glutathione ratio (GSH/GSSG) in brain. The results show that exposure to a very low dose of particulate silver generates mild oxidative stress in the brain but not in the liver of rats, indicating a role of oxidative stress in AgNP-induced neurotoxicity. PMID- 27658322 TI - The risk of chronic kidney disease and mortality are increased after community acquired acute kidney injury. AB - We investigated whether community-acquired acute kidney injury encountered in a tertiary hospital emergency department setting increases the risk of chronic kidney disease (CKD) and mortality, and whether plasma biomarkers could improve the prediction of those adverse outcomes. In a prospective cohort study, we enrolled 616 patients at admission to the emergency department and followed them for a median of 62.1 months. Within this cohort, 130 patients were adjudicated as having acute kidney injury, 159 transient azotemia, 15 stable CKD, and 312 normal renal function. Serum cystatin C and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at index admission. After adjusting for clinical variables, the risk of developing CKD stage 3, as well as the risk of death, were increased in the acute kidney injury group (hazard ratio [HR], 5.7 [95% confidence interval, 3.8-8.7] and HR, 1.9 [95% confidence interval, 1.3-2.8], respectively). The addition of serum cystatin C increased the ability to predict the risk of developing CKD stage 3, and death (HR, 1.5 [1.1-2.0] and 1.6 [1.1 2.3], respectively). The addition of plasma NGAL resulted in no improvement in predicting CKD stage 3 or mortality (HR, 1.0 [0.7-1.5] and 1.2 [0.8-1.8], respectively). The risk of developing CKD stage 3 was also significantly increased in the transient azotemia group (HR, 2.4 [1.5-3.6]). Thus, an episode of community acquired acute kidney injury markedly increases the risk of CKD, and moderately increases the risk of death. Our findings highlight the importance of follow-up of patients with community acquired acute kidney injury, for potential early initiation of renal protective strategies. PMID- 27658325 TI - Cyto-genotoxicity and oxidative stress induced by zinc oxide nanoparticle in human lymphocyte cells in vitro and Swiss albino male mice in vivo. AB - ZnO-np has immense potential and application in cosmetic and health care sectors. Hence it was imperative to assess the toxicity/safety of these nanoparticles. In this study, we have evaluated the effects of ZnO-np in human peripheral blood mononuclear cells (PBMCs) in vitro and in Swiss albino male mice in vivo for cyto genotoxicity and oxidative damage. In vitro results showed that ZnO-nps were weakly genotoxic, induced significant decrease in mitochondrial membrane potential and was capable of ROS generation, leading to apoptosis. In bone marrow cells in vivo, reduction of mitochondrial membrane potential (MMP), increased oxidative stress and G0/G1 cell cycle arrest was observed along with chromosome aberrations and micronuclei formation. In liver cells DNA damage and induction of oxidative stress with concurrent decrease in inhibition of antioxidant enzymes were noted. These in vitro and in vivo results demonstrated that ZnO-np induced genotoxic response and ROS production leading to apoptotic cell death and established a good co-relation between the two biological systems. More importantly, the results stress on the need of multiple endpoint assay approaches, with an in vitro-in vivo study design to assess nanoparticle toxicology. PMID- 27658326 TI - Acute vanishing bile duct syndrome after the use of ibuprofen. AB - We present a case report of a 7-year-old patient who developed toxic epidermal necrolysis (TEN) and vanishing bile duct syndrome (VBDS) after oral ibuprofen intake. Acute VBDS is a rare disease with unknown aetiology, often presenting with progressive loss of the intrahepatic biliary tract. TEN is an immune complex mediated hypersensitivity reaction involving the skin and mucosa, which is induced by drugs or infectious diseases, sometimes leading to systemic symptoms. The patient in this case report was treated with supportive care, a steroid and ursodeoxycholic acid, with complete recovery observed by the end of the 8th month. This case report suggests that ibuprofen can cause acute vanishing duct syndrome. PMID- 27658327 TI - Liver research in the International Space Station. PMID- 27658328 TI - A case of hepatic portal venous gas after colonoscopy. AB - Hepatic portal venous gas (HPVG) is a rare radiologic finding that is usually precipitated by intestinal ischaemia, intra-abdominal abscesses, necrotising enterocolitis, abdominal trauma, infectious enteritis, and inflammatory bowel disease. In this study, we present a case of HPVG in a 66-year-old female patient who underwent colonoscopy for evaluation of haematochezia and a review of the literature focused on HPVG following colonoscopy. PMID- 27658329 TI - What Do Patients Tweet About Their Mammography Experience? AB - RATIONALE AND OBJECTIVE: The purpose of this study was to evaluate themes related to patients' experience in undergoing mammography, as expressed on Twitter. METHODS: A total of 464 tweets from July to December 2015 containing the hashtag #mammogram and relating to a patient's experience in undergoing mammography were reviewed. RESULTS: Of the tweets, 45.5% occurred before the mammogram compared to 49.6% that occurred afterward (remainder of tweets indeterminate). However, in patients undergoing their first mammogram, 32.8% occurred before the examination, whereas in those undergoing follow-up mammogram, 53.0% occurred before the examination. Identified themes included breast compression (24.4%), advising other patients to undergo screening (23.9%), recognition of the health importance of the examination (18.8%), the act of waiting (10.1%), relief regarding results (9.7%), reflection that the examination was not that bad (9.1%), generalized apprehension regarding the examination (8.2%), interactions with staff (8.0%), the gown (5.0%), examination costs or access (3.4%), offering or reaching out for online support from other patients (3.2%), perception of screening as a sign of aging (2.4%), and the waiting room or waiting room amenities (1.3%). Of the tweets, 31.9% contained humor, of which 56.1% related to compression. Themes that were more common in patients undergoing their first, rather than follow-up, mammogram included breast compression (16.4% vs 9.1%, respectively) and that the test was not that bad (26.2% vs 7.6%, respectively). CONCLUSION: Online social media provides a platform for women to share their experiences and reactions in undergoing mammography, including humor, positive reflections, and encouragement of others to undergo the examination. Social media thus warrants further evaluation as a potential tool to help foster greater adherence to screening guidelines. PMID- 27658331 TI - Terminal QRS distortion is present in anterior myocardial infarction but absent in early repolarization. AB - BACKGROUND: Early repolarization (ER) and acute left anterior descending artery occlusion (LADO) may be difficult to distinguish. Terminal QRS distortion (TQRSD), defined by the absence of both an S wave and J wave in either of leads V2 or V3, is often present in anterior ST-segment elevation myocardial infarction. We hypothesized that this finding would always be absent in ER. METHODS: This was a retrospective analysis of electrocardiograms (ECGs) of consecutive patients who presented to the emergency department with ischemic symptoms and had a cardiologist interpretation of "benign ER" on the initial emergency department ECG. All ECGs were scrutinized for the presence of an S wave and a J wave in leads V2 and V3. Differences in S-wave amplitudes between complexes with and without J waves were analyzed using nonparametric Mann-Whitney testing and confidence intervals around a proportion. RESULTS: One hundred seventy-one patients were identified with benign ER. Zero of 171 had TQRSD (specificity for LADO, 100%; 95% confidence interval, 97.8-100). In lead V2, S waves were absent in only 1 of 171 ECGs; however, in that ECG, a J wave measuring 0.5 mm was present. In lead V3, S waves were absent in 16 ECGs, but all of these ECGs had J waves. When J waves were absent in leads V2 or V3, the corresponding S waves were deeper than S waves in QRS complexes with J waves. CONCLUSION: Terminal QRS distortion was never observed in benign ER. Based on previous studies indicating the presence of TQRSD in LADO, it was, thus, 100% specific to LADO when the differential diagnosis was acute myocardial infarction vs ER. PMID- 27658330 TI - SYNTAX Score Derived From Coronary CT Angiography for Prediction of Complex Percutaneous Coronary Interventions. AB - RATIONALE AND OBJECTIVES: SYNTAX score is a useful metric determined at the time of invasive coronary angiography (ICA) to assess the complexity of coronary artery disease, and improves prediction of complications at the time of percutaneous complex intervention (PCI). We aimed to determine whether SYNTAX score can be reliably determined from coronary computed tomography angiography (CCTA) and whether a CCTA-derived SYNTAX score can predict complex PCI. MATERIALS AND METHODS: SYNTAX scores were calculated on per-patient, per-vessel, and per segment basis in 154 consecutive patients who underwent CCTA and ICA. PCI complexity in 113 patients who underwent intervention was defined by total fluoroscopy time and contrast volume. RESULTS: Compared to ICA, CCTA detected 285 of 302 (94%) obstructive lesions in 230 vessels, for which PCI was performed for 154 lesions in 131 vessels. Overall, on a per-patient basis, ICA-derived SYNTAX score was lower in comparison to CCTA-derived score (10.2 +/- 8.0 vs 10.9 +/- 8.3, P = 0.001). As compared to lesions in the lowest CCTA-derived segmental SYNTAX tertile, lesions in the highest tertile required longer fluoroscopy time (17.5 +/- 12 min vs 11.5 +/- 7.9 min, P = 0.01) and greater contrast volume (215.4 +/- 125.5 mL vs 144.3 +/- 49 mL, P = 0.02). CONCLUSION: SYNTAX scores derived from CCTA are concordant with those derived from ICA and correspond with complex PCI. PMID- 27658332 TI - Prehospital therapeutic hypothermia after out-of-hospital cardiac arrest: a systematic review and meta-analysis. AB - BACKGROUND: The effectiveness and safety of the infusion of ice-cold fluids for prehospital hypothermia in cardiac arrest victims are unclear. This study assessed its effects in adult victims of out-of-hospital cardiac arrest. METHODS: An online search of PubMed and Cochrane Library databases was performed. Cooling methods were limited to ice-cold fluid perfusion. Randomized controlled trials were included in this review. The main outcomes were body temperature at hospital arrival, survival to hospital discharge, neurological recovery, incidence of pulmonary edema, and the rate of rearrest. RESULTS: Among 1155 citations, 5 studies were included in this meta-analysis. The pooled analysis of these studies revealed no differences in survival to hospital discharge, favorable neurological outcomes, and incidence of pulmonary edema between the treatment group and control group. There were significant differences in body temperature at hospital arrival (I2 = 0.0%, chi2 = 2.58, MD = -0.760, 95% confidence interval = -0.938 to -0.581, P < .001) and the rate of rearrest (I2 = 0.0%, chi2 = 0.69, 95% confidence interval = 1.109 to 1.479, P = .031). CONCLUSIONS: Prehospital therapeutic hypothermia induced by intravenous infusion of ice-cold fluids in patients with out-of-hospital cardiac arrest decreased body temperature at hospital arrival but did not improve survival to hospital discharge and favorable neurological outcomes. Ice-cold fluid infusion did not increase the incidence of pulmonary edema but increased the incidence of rearrests. PMID- 27658333 TI - STEMI in a young female? Consider spontaneous peripartum coronary artery dissection. PMID- 27658334 TI - Sexual enhancer-induced vision loss. PMID- 27658335 TI - In search of the optimal Valsalva maneuver position for the treatment of supraventricular tachycardia. PMID- 27658336 TI - A Review of Singing Voice Subsystem Interactions-Toward an Extended Physiological Model of "Support". AB - During phonation, the respiratory, the phonatory, and the resonatory parts of the voice organ can interact, where physiological action in one subsystem elicits a direct effect in another. Here, three major subsystems of these synergies are reviewed, creating a model of voice subsystem interactions: (1) Vocal tract adjustments can influence the behavior of the voice source via nonlinear source tract interactions; (2) The type and degree of vocal fold adduction controls the expiratory airflow rate; and (3) The tracheal pull caused by the respiratory system affects the vertical larynx position and thus the vocal tract resonances. The relevance of the presented model is discussed, suggesting, among others, that functional voice building work concerned with a particular voice subsystem may evoke side effects or benefits on other subsystems, even when having a clearly defined and isolated physiological target. Finally, four seemingly incongruous historic definitions of the concept of singing voice "support" are evaluated, showing how each of these pertain to different voice subsystems at various levels of detail. It is argued that presumed discrepancies between these definitions can be resolved by putting them into the wider context of the subsystem interaction model presented here, thus offering a framework for reviewing and potentially refining some current and historical pedagogical approaches. PMID- 27658337 TI - Effect of Performance Time of the Semi-Occluded Vocal Tract Exercises in Dysphonic Children. AB - OBJECTIVE: This study aimed to verify the effects of execution time on auditory perceptual and acoustic responses in children with dysphonia completing straw phonation exercises. STUDY DESIGN: A randomized, prospective, comparative intra subject study design was used. METHODS: Twenty-seven children, ranging from 5 to 10 years of age, diagnosed with vocal cord nodules or cysts, were enrolled in the study. All subjects included in the Experimental Group were also included in the Control Group which involved complete voice rest. Sustained vowels (/a/e/epsilon/e/) counting from 1 to 10 were recorded before the exercises (m0) and then again after the first (m1), third (m3), fifth (m5), and seventh (m7) minutes of straw phonation exercises. The recordings were randomized and presented to five speech therapists, who evaluated vocal quality based on the Grade Roughness Breathiness Asthenia/Strain Instability scale. For acoustic analysis, fundamental frequency, jitter, shimmer, glottal to noise excitation ratio, and noise parameters were analyzed. RESULTS: Reduced roughness, breathiness, and noise measurements as well as increased glottal to noise excitation ratio were observed in the Experimental Group after 3 minutes of exercise. Reduced grade of dysphonia and breathiness were noted after 5 minutes. CONCLUSION: The ideal duration of straw phonation in children with dysphonia is from 3 to 5 minutes. PMID- 27658338 TI - Assessment of Grade of Dysphonia and Correlation With Quality of Life Protocol. AB - OBJECTIVE: The main objective of this study is to check the correlation between vocal self-assessment and results of the Voice-Related Quality of Life (V-RQOL) protocol, and whether there is a correlation between perceptual vocal assessment made by voice therapists and the results from the V-RQOL protocol. STUDY DESIGN: The study included 245 subjects with vocal complaints. This was a prospective analytical clinical study. METHODS: Vocal perceptual assessment of each subject with dysphonia was made by three voice therapists, followed by self-assessment made by the subjects themselves, and the application of the V-RQOL protocol. RESULTS: The results have shown poor level of agreement between vocal assessment made by the voice therapists and self-assessment made by the subjects. The statistical analysis indicated that the results of V-RQOL protocol showed significant correlation with the vocal assessment made by the voice therapists and the self-assessment by the subjects. CONCLUSIONS: The agreement between the assessments was low and variable; age, gender, professional voice use, and clinical laryngoscopic diagnosis did not influence the agreement level. Protocol V-RQOL is sensitive to vocal assessment made by the voice therapists and self assessment made by the patient. PMID- 27658339 TI - Data Collection of Infant Cries for Research and Analysis. AB - Analysis of infants cries may help in identifying the needs of infants such as hunger, pain, sickness, etc and thereby develop a tool or possible mobile application that can help the parents in monitoring the needs of their infant. Analysis of cries of infants who are suffering from neurologic disorders and severe diseases, which can later on result in motor and mental handicap, may prove helpful in early diagnosis of pathologies and protect infants from such disorders. The development of an infant cry corpus is necessary for the analysis of infant cries and for the development of infant cry tools. Infant cry database is not available commercially for research, which limits the scope of research in this area. Because the cry characteristics changes with many factors such as reason for crying, infant's health and weight, age, etc, care is required while designing a corpus for a particular research application of infant cry analysis and classification. In this paper, the ideal characteristics of the corpus are proposed along with factors influencing infant cry characteristics, and experiences during data collection are shared. This study may help other researchers to build an infant cry corpus for their specific problem of study. Justification of the proposed characteristics is also given along with suitable examples. PMID- 27658340 TI - Very late relapse in a patient with acute promyelocytic leukemia (APL) rescued with a chemotherapy-free protocol. PMID- 27658341 TI - Hypoadiponectinemia, elevated iron and high-sensitivity C-reactive protein levels and their relation with prostate size in benign prostatic hyperplasia. AB - Elevated iron, high-sensitivity C-reactive protein (CRP) and hypoadiponectinemia are known to initiate tumour development. There is paucity of data regarding the above-mentioned parameters and their relation with prostate size in benign prostatic hyperplasia (BPH). The present study was designed to assess the levels of iron, hs-CRP and adiponectin levels and their association with prostate size in BPH patients. A total of 37 BPH cases and 36 controls were enrolled in the study. Iron, hs-CRP and adiponectin were estimated in both the groups. Iron and hs-CRP were significantly increased and adiponectin was significantly reduced in BPH cases when compared with controls. Iron (r = .397, p = .015), hs-CRP (r = .341, p = .039) and adiponectin (r = -.464, p = .004) were significantly associated with prostate size in BPH cases. Multivariate linear regression analysis showed that iron acts as predictor of prostate size in BPH (R2 = 0.395, beta = 0.526, p = .001). We conclude that iron and hs-CRP are elevated and adiponectin is reduced in BPH cases and associated with prostate size. PMID- 27658342 TI - Growth, productivity, and relative extinction risk of a data-sparse devil ray. AB - Devil rays (Mobula spp.) face intensifying fishing pressure to meet the ongoing international demand for gill plates. The paucity of information on growth, mortality, and fishing effort for devil rays make quantifying population growth rates and extinction risk challenging. Furthermore, unlike manta rays (Manta spp.), devil rays have not been listed on CITES. Here, we use a published size-at age dataset for the Spinetail Devil Ray (Mobula japanica), to estimate somatic growth rates, age at maturity, maximum age, and natural and fishing mortality. We then estimate a plausible distribution of the maximum intrinsic population growth rate (rmax) and compare it to 95 other chondrichthyans. We find evidence that larger devil ray species have low somatic growth rate, low annual reproductive output, and low maximum population growth rates, suggesting they have low productivity. Fishing rates of a small-scale artisanal Mexican fishery were comparable to our estimate of rmax, and therefore probably unsustainable. Devil ray rmax is very similar to that of manta rays, indicating devil rays can potentially be driven to local extinction at low levels of fishing mortality and that a similar degree of protection for both groups is warranted. PMID- 27658343 TI - No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment. AB - A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes. PMID- 27658344 TI - Transfusion medicine in the Formosa Fun Coast water park explosion: The role of combined tissue and blood banking. AB - The Formosa Fun Coast explosion, occurring in a recreational water park located in the Northern Taiwan on 27 June 2015, made 499 people burn-injured. For those who had severe burn trauma, surgical intervention and fluid resuscitation were necessary, and potential blood transfusion therapy could be initiated, especially during and after broad escharotomy. Here, we reviewed the literature regarding transfusion medicine and skin grafting as well as described the practicing experience of combined tissue and blood bank in the burn disaster in Taiwan. It was reported that patients who were severely burn-injured could receive multiple blood transfusions during hospitalization. Since the use of skin graft became a mainstay alternative for wound coverage after the early debridement of burn wounds at the beginning of the 20th century, the development of tissue banking program was initiated. In Taiwan, the tissue banking program was started in 2006. And the first combined tissue and blood bank was established in Far Eastern Memorial Hospital in 2010, equipped with the non-sterile, clean and sterile zones distinctly segregated with a unidirectional movement in the sterile area. The sterile zone was a class 10000 clean room equipped with high efficiency particulate air filter (HEPAF) and positive air pressure ventilation. The combined tissue and blood bank has been able to provide the assigned blood products and tissue graft timely and accurately, with the concepts of centralized management. In the future, the training of tissue and blood bank technicians would be continued and fortified, particularly on the regulation and quality control for further bio- and hemovigilance. PMID- 27658345 TI - Biography of Professor Hitoshi Ohto, the Invited Editor for this Theme, Disasters and Blood Transfusion. PMID- 27658346 TI - Pharmacological characterization of a series of aryl-sulfonamide derivatives that potently and selectively inhibit monoacylglycerol acyltransferase 2. AB - Monoacylglycerol acyltransferase (MGAT) 2 is an endoplasmic reticulum membrane enzyme that catalyzes the synthesis of diacylglycerol (DAG) from fatty acyl-CoA and monoacylglycerol as substrates. It is important for the resynthesis of triacylglycerol in the intestine. We have identified a series of aryl-sulfonamide MGAT2 inhibitors and demonstrated pharmacological inhibition of MGAT2 improved hyperlipidemia, obesity, and diabetes in animal models. However, its mechanism of action has not been elucidated in molecular and cellular levels. In the present study, we have characterized a series of aryl-sulfonamide derivatives that potently and selectively inhibit human MGAT2 and determined their pharmacological profiles. Analyses on the molecular mechanism of a representative aryl sulfonamide MGAT2 inhibitor revealed a reversible inhibitory activity and a binding activity to MGAT2. The aryl-sulfonamide derivatives exhibited potent inhibitory activities against both human and mouse intestinal MGAT activities, which were correlated to those determined using recombinant human and mouse MGAT enzymes. We have developed a cellular assay using Liquid Chromatography-Mass Spectrometry and confirmed that the aryl-sulfonamide derivatives suppressed DAG synthesis in the cellular context. We have thus elucidated their pharmacological profiles and provided the fundamental clues for understanding the molecular and cellular actions of the aryl-sulfonamide MGAT2 inhibitors. PMID- 27658347 TI - Effect of D609 on the expression of GADD45beta protein: Potential inhibitory role in the growth of glioblastoma cancer stem like cells. AB - GADD45beta (Growth Arrest and DNA Damage inducible protein) is a stress activated protein which plays an important role in regulating apoptosis, proliferation, DNA repair and potentially may have a role in cancer. In this study we examined the role of anti-oxidative stress on the expression of GADD45beta in glioma stem-like cells (GSC). We show that patient derived GSCs have high survival in the absence of exogenous growth factors. Addition of D609 (Tricyclodecan-9-yl-xanthogenate), a known anti-oxidative compound, to GSCs reduced the cellular ATP content with significant effects observed when GSCs were cultured in growth factor free medium. D609 exposure also resulted in a decrease in the protein and an increase in mRNA of GADD45beta with a concomitant decline in the survival of cells. However, under similar conditions the phosphorylation of p38 MAP kinase (stress activated MAP kinase), a downstream target of GADD45beta, was significantly enhanced in response to D609. Therefore it appears that GADD45beta might play a role in glioma stem cell survival and that p38 MAP kinase may not be directly activated by GADD45beta. Together these observations suggest that anti-oxidative compounds like D609 can target GADD45beta which may be one strategy to curtail the growth of glioma stem like cells. PMID- 27658348 TI - Mediation of self-regulation and mood in the relationship of changes in high emotional eating and nutritional behaviors: Moderating effects of physical activity. AB - High emotional eating (EE) is prevalent in women with obesity. A previous study's subsample of obese women classified as high emotional eaters participated in either a physical activity-focused experimental (n = 29) or an educationally focused comparison (n = 22) behavioral treatment and was assessed over phases of expected weight loss (baseline-month 6) and short- and long-term regain (months 6 12 and 6-24, respectively). The study's aim was to assess theory-based psychological and behavioral mediation and moderation of changes in nutritional behaviors via emotional eating change in order to inform behavioral weight-loss treatments. During the weight-loss phase, significant improvements in eating self regulation and mood significantly mediated the relationship of reduced EE and intake of both fruits and vegetables (FV) and sweets. Self-regulation was a significant independent mediator. Physical activity significantly moderated the relationship between EE and self-regulation changes. All variables demonstrated large positive effects and significant time * group interactions favoring the experimental group. During the short and long-term phases of expected weight regain, there were no significant changes in FV intake, although consumption of sweets significantly increased during months 6-24. Change in FV and sweets significantly predicted weight change, which was significantly greater in the experimental vs. comparison group over both the initial 6 months (-6.1% vs. 2.6%) and full 24 months of the study (-7.6% vs. -1.3%). Findings suggest that behavioral treatments should address EE through improvements in self-regulation and mood, and supported physical activity will aid in that process. The need for an improved understanding of weight-loss maintenance remains. PMID- 27658349 TI - A quantum approach to homomorphic encryption. AB - Encryption schemes often derive their power from the properties of the underlying algebra on the symbols used. Inspired by group theoretic tools, we use the centralizer of a subgroup of operations to present a private-key quantum homomorphic encryption scheme that enables a broad class of quantum computation on encrypted data. The quantum data is encoded on bosons of distinct species in distinct spatial modes, and the quantum computations are manipulations of these bosons in a manner independent of their species. A particular instance of our encoding hides up to a constant fraction of the information encrypted. This fraction can be made arbitrarily close to unity with overhead scaling only polynomially in the message length. This highlights the potential of our protocol to hide a non-trivial amount of information, and is suggestive of a large class of encodings that might yield better security. PMID- 27658350 TI - Nail involvement as a negative prognostic factor in biological therapy for psoriasis: a retrospective study. AB - BACKGROUND: Psoriasis (Pso) has a strong impact on quality of life and a positive association has been reported between nail psoriasis (NP) and more severe disease, together with a longer duration of skin lesions. The treatment of NP represents a challenge and biological therapy can be recommended for severe disease. OBJECTIVE: The first end point of this retrospective study was to evaluate the time to achieve Psoriasis Area Severity Index (PASI) 75 in patients with and without NP treated with biological therapy. The second end point was to evaluate the efficacy of biological therapy to improve NP. METHODS: A total of 127 patients (88 men and 39 women) with moderate to severe Pso referring to our Service between 2007 and 2014 were included. Inclusion criteria were age >=18 years and a 24 week treatment. The outcome variable was achievement of PASI 75 at 24 weeks with and without NP. All patients were treated with topical therapy and one of four different biological treatments: adalimumab (44.09%), etanercept (18.11%), infliximab (13.39%) and ustekinumab (24.41%). Physical examinations were performed every 4 weeks, and at each visit, the clinician assessed the PASI and Nail Psoriasis Severity Index (NAPSI). RESULTS: At multivariate Cox regression analysis, a smaller proportion of patients with NP achieved PASI 75 at 24 weeks than patients without NP when adjusted for the epidemiological, clinical features and biological treatment received. With all biological drugs, the NAPSI score began to improve already after 8 weeks (from 18.53 at week 0-2.83 at week 24). CONCLUSION: Patients with NP reach PASI 75 more slowly than patients without NP. Clinicians should therefore consider that treatment with a biological agent may require a longer period before reaching a satisfying therapeutical goal. Nevertheless, adalimumab, infliximab, ustekinumab and etanercept demonstrated their equal effectiveness in reducing the NAPSI score. PMID- 27658352 TI - Contemporary evidence-based practice in Canadian emergency medical services: a vision for integrating evidence into clinical and policy decision-making. AB - Nationally, emphasis on the importance of evidence-based practice (EBP) in emergency medicine and emergency medical services (EMS) has continuously increased. However, meaningful incorporation of effective and sustainable EBP into clinical and administrative decision-making remains a challenge. We propose a vision for EBP in EMS: Canadian EMS clinicians and leaders will understand and use the best available evidence for clinical and administrative decision-making, to improve patient health outcomes, the capability and quality of EMS systems of care, and safety of patients and EMS professionals. This vision can be implemented with the use of a structure, process, system, and outcome taxonomy to identify current barriers to true EBP, to recognize the opportunities that exist, and propose corresponding recommended strategies for local EMS agencies and at the national level. Framing local and national discussions with this approach will be useful for developing a cohesive and collaborative Canadian EBP strategy. PMID- 27658351 TI - The brain, obesity and addiction: an EEG neuroimaging study. AB - Obesity is among the greatest challenges facing healthcare systems with 20% of the world's population afflicted. Great controversy exists whether obesity can be regarded as an addictive disorder or not. Recently the Yale Food Addiction Scale questionnaire has been developed as a tool to identify individuals with traits of addiction towards food. Using clinical and source localized EEG data we dichotomize obesity. Brain activity in food-addicted and non-food-addicted obese people is compared to alcohol-addicted and non-addicted lean controls. We show that food addiction shares common neural brain activity with alcohol addiction. This 'addiction neural brain activity' consists of the dorsal and pregenual anterior cingulate cortex, parahippocampal area and precuneus. Furthermore, common neural obesity neural brain activity exists as well. The 'obesity neural brain activity' consists of dorsal and pregenual anterior cingulate cortex, posterior cingulate extending into the precuneus/cuneus as well as the parahippocampal and inferior parietal area. However food-addicted differ from non food-addicted obese people by opposite activity in the anterior cingulate gyrus. This food addiction and non-food-addiction obesity dichotomy demonstrates there is at least 2 different kinds of obesity with overlapping network activity, but different in anterior cingulate cortex activity. PMID- 27658353 TI - Mangiferin: A review of sources and interventions for biological activities. AB - Xanthones are naturally synthesized in various biological systems such as plants, lichens, and fungi and are stored as by-products. In addition to taxonomic significance they are also important in the treatment/management of a number of human disorders. Mangiferin and its derived lead molecule have never qualified for use in a clinical trial despite a number of pharmacological studies that have proven its effectiveness as an antioxidant, analgesic, antidiabetic, antiproliferative, chemopreventive, radioprotective, cardiotonic, immunomodulatory, and diuretic. For centuries in the traditional practice of medicine in India and China the use of plants containing mangiferin has been a major component for disease management and health benefits. While it resembles biflavones, the C-glucosyl xanthone (mangiferin) has great nutritional and medicinal significance due to its unique structural characteristics. The C glycoside link of mangiferin, mimicked to nucleophilic phloroglucinol substitution, facilitates its bioavailability and also is responsible for its antioxidant properties. Researchers have also utilized its xanthonic framework for both pharmacophoric backbone and for its use as a substitution group for synthesis and prospects. To date more than 500 derivatives using about 80 reactions have been generated. These reactions include: lipid peroxidation, phosphorylation, glycosylation, methylation, fermentation, deglycosylation, hydrolysis, polymerization, sulfation, acylation, etherification, peroxidation among others. Multiple studies on efficacy and safety have increased the global demand of mangiferin-based food supplements. This review highlights the distribution of mangiferin in plants, its isolation, and assay methods applicable to different sample matrices. In addition we include updates on various strategies and derived products intended for designated pharmacological actions. (c) 2016 BioFactors, 42(5):504-514, 2016. PMID- 27658355 TI - Internuclear Bridging of Erythroid Precursors in the Peripheral Blood Smear of a Patient with Primary Myelofibrosis. PMID- 27658354 TI - Genetic characterization of two fully sequenced multi-drug resistant plasmids pP10164-2 and pP10164-3 from Leclercia adecarboxylata. AB - We previously reported the complete sequence of the resistance plasmid pP10164 NDM, harboring blaNDM (conferring carbapenem resistance) and bleMBL (conferring bleomycin resistance), which is recovered from a clinical Leclercia adecarboxylata isolate P10164 from China. This follow-up work disclosed that there were still two multidrug-resistant (MDR) plasmids pP10164-2 and pP10164-3 coexisting in this strain. pP10164-2 and pP10164-3 were completely sequenced and shown to carry a wealth of resistance genes, which encoded the resistance to at least 10 classes of antibiotics (beta-lactams. macrolides, quinolones, aminoglycosides, tetracyclines, amphenicols, quaternary ammonium compounds, sulphonamides, trimethoprim, and rifampicin) and 7 kinds of heavy mental (mercury, silver, copper, nickel, chromate, arsenic, and tellurium). All of these antibiotic resistance genes are associated with mobile elements such as transposons, integrons, and insertion sequence-based transposable units, constituting a total of three novel MDR regions, two in pP10164-2 and the other one in pP10164-3. Coexistence of three resistance plasmids pP10164-NDM, pP10164-2 and pP10164-3 makes L. adecarboxylata P10164 tend to become extensively drug resistant. PMID- 27658356 TI - Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation. AB - Leucine-rich repeat kinase 2 (LRRK2) kinase activity is increased in several pathogenic mutations, including the most common mutation, G2019S, and is known to play a role in Parkinson's disease (PD) pathobiology. This has stimulated the development of potent, selective LRRK2 kinase inhibitors as one of the most prevailing disease-modifying therapeutic PD strategies. Although several lines of evidence support beneficial effects of LRRK2 kinase inhibitors, many questions need to be answered before clinical applications can be envisaged. Using six different LRRK2 kinase inhibitors, we show that LRRK2 kinase inhibition induces LRRK2 dephosphorylation and can reduce LRRK2 protein levels of overexpressed wild type and G2019S, but not A2016T or K1906M, LRRK2 as well as endogenous LRRK2 in mouse brain, lung and kidney. The inhibitor-induced reduction in LRRK2 levels could be reversed by proteasomal inhibition, but not by lysosomal inhibition, while mRNA levels remained unaffected. In addition, using LRRK2 S910A and S935A phosphorylation mutants, we show that dephosphorylation of these sites is not required for LRRK2 degradation. Increasing our insight in the molecular and cellular consequences of LRRK2 kinase inhibition will be crucial in the further development of LRRK2-based PD therapies. PMID- 27658357 TI - New steroids from Anemarrhena asphodeloides rhizome and their alpha-glucosidase inhibitory activity. AB - Two new steroids were isolated from acid hydrolysis residue of the rhizomes of Anemarrhena asphodeloides. Their structures were identified on the basis of several spectroscopic analysis approaches including 1D, 2D-NMR techniques, and MS data, and by the comparison of spectral data of the known compounds. The biological activities of these two isolated compounds were explored on alpha glucosidase. Compound 1 displayed 4.7 folds inhibitory activity against alpha glucosidase compared with the positive control acarbose. PMID- 27658358 TI - Falling and fall risk in adult patients with severe haemophilia. AB - : The objective of this study was to define fall rates and to identify possible fall risk factors in adult patients with severe haemophilia. PATIENTS, MATERIAL, METHODS: 147 patients with severe haemophilia A and B were evaluated using a standardized test battery consisting of demographic, medical and clinical variables and fall evaluation. RESULTS: 41 (27.9 %) patients reported a fall in the past 12 months, 22 (53.7 %) of them more than once. Young age, subjective gait insecurity and a higher number of artificial joints seem to be risk factors for falling. CONCLUSION: Falls seem to be a common phenomenon in patients with severe haemophilia. Fall risk screening and fall prevention should be implemented into daily practice. PMID- 27658359 TI - [An assessment of the management of spasticity in Spain: the 5E Study]. AB - INTRODUCTION: Although spasticity is a disabling complication of high incidence, there is a lack of either regional or national epidemiological studies in Spain evaluating its management. AIM: To evaluate the management of spasticity in Spain. PATIENTS AND METHODS: An epidemiological, observational, multicenter, and retrospective study involving 49 rehabilitation services of public and private hospitals was designed. RESULTS: Two hundred and thirty-five patients from 49 centers, with evidence of upper (UL) or lower limb (LL) spasticity with one valid baseline visit and at least one follow-up visit, were included. Among the patients included in the study 148 (62.9%) have post stroke spasticity; 79 (33.6%) have LL spasticity, 38 (16.1%) UL, and 118 (50.3%) in both. At baseline, Modified Ashworth Scale, goniometry, Visual Analog Scale for pain and Tardieu Scale had been performed in 164 (69.8%), 99 (42.1%), 85 (36.2%), and 26 (11.1%) patients, respectively. A 93.8% (IC 95%: 81.4-97.6%) of the centers accurately defined the treatment goals and 52% of the objectives were agreed with the patient. Botulinum A toxin was administered in 186 (79.1%) of patients; 49 (20.9%) patients were treated with oral antispastic medications and 93 (39.6%) were under physiotherapy treatment. CONCLUSIONS: Most of the patients have post stroke spasticity. Moreover, botulinum A toxin was the most commonly treatment applied to patients with spasticity. The results demonstrate that the management of spasticity varies significantly across the different centers participating in the study. PMID- 27658360 TI - [Prognostic implications of folliculo-stellate cells in pituitary adenomas: relationship with tumoral behavior]. AB - INTRODUCTION: Despite progress in understanding its pathogenesis, there has not yet been found any independent predictive marker of aggressive behavior of pituitary adenomas, to facilitate the treatment and monitoring of patients. AIM: To analyze the expression of folliculo-stellate cells by immunostaining with S 100 protein, in a series of patients with pituitary adenomas followed for at least seven years. PATIENTS AND METHODS: A retrospective study of 51 patients diagnosed with a pituitary adenoma between 2006 and 2008 was performed, according to current criteria established by the World Health Organization. The S-100 expression in folliculo-stellate cells was immunohistochemically evaluated, correlating it with clinico-radiological and histopathological tumor parameters and post-operative progression/recurrence. RESULTS: Of 51 tumors, 40 were classified as typical and 11 as atypical pituitary adenomas. Most typical pituitary adenomas showed positive folliculo-stellate cells for S-100 (mean: 3.93%); atypical had little/no cell S-100 positive (mean: 0.83%). There were no significant differences in the expression of S-100 with respect to age or sex of the patient, size, invasiveness or post-operative tumor recurrence. CONCLUSIONS: In our study group, with the exception of non-functioning adenomas immunopositive for prolactin, with the lowest and highest average of all subtypes in both groups (typical 0.25% vs atypical 9.24%; p = 0.0028), the predictive factor of tumor aggressiveness for pituitary adenomas, is not represented by a low value of S-100 in folliculo-stellate cells, not allowing select patients for intensive post operative treatment. PMID- 27658361 TI - [Description of a series of hospital patients with a spinal fistula]. AB - INTRODUCTION: Although spinal fistulas account for 70% of all spinal arteriovenous malformations, they are an underdiagnosed condition. The arteriovenous shunt produces vascular congestion that gives rise to a progressive myelopathy, sometimes irreversible if it is not treated in the early stages. AIM: To describe the clinicoradiological characteristics of a series of patients with spinal fistulas. PATIENTS AND METHODS: A retrospective search was conducted for patients diagnosed with a spinal fistula who were hospitalised in the neuroscience area of a tertiary care hospital. RESULTS: A total of 19 patients (7 females and 12 males) were identified, with a mean age of 56 years. The spinal fistula was type I in 79% of patients, and a dorsal location was the most frequent. Most of the cases (90%) presented a progressive course. Magnetic resonance imaging was used in the diagnosis in 74% of the patients. In four cases angiography was required to reach a diagnosis, and in one of them it was necessary to perform an intraoperative biopsy. Three lumbar punctures were performed, two of which revealed lymphocytic pleocytosis and high protein levels in cerebrospinal fluid. The average diagnostic delay was nine months. Seventy nine per cent of the patients were treated and only 10% of them improved. CONCLUSIONS: When faced with a clinical picture suggestive of a spinal fistula, a diagnostic spinal angiography must be carried out, although the patient under study may present atypical cerebrospinal fluid characteristics and normal results in magnetic resonance imaging of the spinal cord. PMID- 27658362 TI - [Aicardi-Goutieres syndrome due to mutation of the IFIH1 gene with pontine involvement. A case report]. AB - INTRODUCTION: Aicardi-Goutieres syndrome is a rare progressive subacute encephalopathy of early onset - generally in the first year of life - characterised by psychomotor retardation, microcephaly, alterations in the white matter of the brain, intracranial calcifications, pleocytosis and elevated levels of interferon alpha in the cerebrospinal fluid. It is associated to an increase in the expression of genes stimulated by interferon in peripheral blood, a fact known as the interferon signature. The levels of genes stimulated by interferon has been postulated as a good biomarker, as they remain high in peripheral blood over time and are more sensitive, in comparison to determinations of interferon alpha and neopterins in cerebrospinal fluid, which descend as of one year of life. To date, mutations have been reported in seven genes that overstimulate the interferon alpha pathway, and the last to be discovered is IFIH1 (interferon induced with helicase C domain 1), with a pattern of dominant autosomal inheritance. CASE REPORT: We present the first case reported in the Hispanic literature caused by a de novo mutation in the IFIH1 gene. The clinical features, studies conducted and review of the clinical, neuroradiological and genetic aspects are described. CONCLUSIONS: The inheritance of the mutations reported for Aicardi-Goutieres syndrome was classically considered as being recessive autosomal, but these findings show that dominant autosomal mutations in the IFIH1 gene can cause the disease. As a previously unreported neuroimaging finding, it presents a lesion consisting in cystic encephalomalacia in the pons. PMID- 27658363 TI - [Migraine and evolutionary theory: paths for a clinical approach]. AB - INTRODUCTION: Migraine is a very common disorder with a raising incidence. The theory of evolution allow us to explain the emergence of the disorder, due to the advantages that the overreactivity to stimulus provided to ancestral groups of Homo sapiens, and a greater presence of the disorder in modern societies, based in the interactions with external factors. Herein we analyze these points. DEVELOPMENT: Design of organisms and their responses to environmental factors emerge to improve survival. Thus pain and headache can be contemplated as homeostatic and adaptative responses. Below 10% of the population has no experience with headache and the migrainous phenotype is quite frequent in secondary headaches and in syndromic forms of migraine. These features can be understood under the next undergrounds: specific neurophysiological data (lack of habituation, sensibilization and low preactivation), genetic features (polygenic disorder with the implication of many gens with a low penetrance, that interact with the environment and are shared with comorbid disorders such as depression and anxiety); and environmental interactions in modern societies (increase in the number of estrogenic cycles and particularly overexposition to stress). CONCLUSIONS: A feature that was an evolutionary advantage has been transformed in a highly prevalent and disabling disorder in modern societies. It is the result of the interaction with internal (estrogenic cycles) and external (stress) stimuli. As a consequence, it becomes a mismatch disorder. The effects appear in childhood through epigenetics. Therefore, therapeutic interventions would yield greater benefits if whole populations were included in educative interventions incorporating these aspects. PMID- 27658364 TI - [XXX Reunion da Sociedade Galega de Neuroloxia. Communications]. PMID- 27658365 TI - [Abdominal pain: an infrequent manifestation of temporal epilepsy]. PMID- 27658366 TI - Rethinking Autonomy: Relationships as a Source of Resilience in a Changing Healthcare System. PMID- 27658367 TI - Two-dimensional flow nanometry of biological nanoparticles for accurate determination of their size and emission intensity. AB - Biological nanoparticles (BNPs) are of high interest due to their key role in various biological processes and use as biomarkers. BNP size and composition are decisive for their functions, but simultaneous determination of both properties with high accuracy remains challenging. Optical microscopy allows precise determination of fluorescence/scattering intensity, but not the size of individual BNPs. The latter is better determined by tracking their random motion in bulk, but the limited illumination volume for tracking this motion impedes reliable intensity determination. Here, we show that by attaching BNPs to a supported lipid bilayer, subjecting them to hydrodynamic flows and tracking their motion via surface-sensitive optical imaging enable determination of their diffusion coefficients and flow-induced drifts, from which accurate quantification of both BNP size and emission intensity can be made. For vesicles, the accuracy of this approach is demonstrated by resolving the expected radius squared dependence of their fluorescence intensity for radii down to 15 nm. PMID- 27658368 TI - Design and synthesis of selective, dual fatty acid binding protein 4 and 5 inhibitors. AB - Dual inhibition of fatty acid binding proteins 4 and 5 (FABP4 and FABP5) is expected to provide beneficial effects on a number of metabolic parameters such as insulin sensitivity and blood glucose levels and should protect against atherosclerosis. Starting from a FABP4 selective focused screening hit, biostructure information was used to modulate the selectivity profile in the desired way and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. With very good pharmacokinetic properties and no major safety alerts, compound 12 was identified as a suitable tool compound for further in vivo investigations. PMID- 27658369 TI - Fluoro analogs of bioactive oxy-sterols: Synthesis of an EBI2 agonist with enhanced metabolic stability. AB - Synthesis of several 7-hydroxy oxysterols and their potential roles as signaling molecules in the innate and adaptive immune responses is discussed. Discovery of a new, fluorinated, synthetic analog of the 7alpha,25-dihydroxycholesterol-the endogenous ligand of GPR 183 (EBI2), a G-protein coupled receptor highly expressed upon Epstein-Barr virus infection is described. Fluoro oxysterol 12 showed good metabolic stability while maintaining excellent EBI2 agonist activity. PMID- 27658370 TI - One-inflation and unobserved heterogeneity in population size estimation. AB - We present the one-inflated zero-truncated negative binomial (OIZTNB) model, and propose its use as the truncated count distribution in Horvitz-Thompson estimation of an unknown population size. In the presence of unobserved heterogeneity, the zero-truncated negative binomial (ZTNB) model is a natural choice over the positive Poisson (PP) model; however, when one-inflation is present the ZTNB model either suffers from a boundary problem, or provides extremely biased population size estimates. Monte Carlo evidence suggests that in the presence of one-inflation, the Horvitz-Thompson estimator under the ZTNB model can converge in probability to infinity. The OIZTNB model gives markedly different population size estimates compared to some existing truncated count distributions, when applied to several capture-recapture data that exhibit both one-inflation and unobserved heterogeneity. PMID- 27658371 TI - Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design. AB - BACKGROUND: In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. OBJECTIVES: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients' experiences with NET and to identify influencing factors on treatment results. METHODS: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the understanding of quantitative outcomes. DISCUSSION: The results of this study will provide more insight into influencing factors for clinical changes in this population. PMID- 27658373 TI - QRB Discovery: introducing original research to QRB. PMID- 27658372 TI - Transcranial focused ultrasound stimulation of human primary visual cortex. AB - Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications. PMID- 27658375 TI - The effect of silver nanoparticles/graphene-coupled TiO2 beads photocatalyst on the photoconversion efficiency of photoelectrochemical hydrogen production. AB - In this work, a novel configuration of the photoelectrochemical hydrogen production device is demonstrated. It is based on TiO2 beads as the primary photoanode material with the addition of a heterostructure of silver nanoparticles/graphene. The heterostructure not only caters to a great improvement in light harvesting efficiency (LHE) but also enhances the charge collection efficiency. For LHE, the optimized cell based on TiO2 beads/Ag/graphene shows a 47% gain as compared to the cell having a photoanode of commercial P25 TiO2 powders. For the charge collection efficiency, there is a pronounced improvement of an impressive value of 856%. The reason for the improvement in light absorption is attributed to either the light scattering of TiO2 beads or the surface plasmonic resonance on the Ag nanoparticles/graphene. The photoconversion efficiency (PCE) of the resulting cells is also presented and discussed. The PCE of the TiO2 beads/Ag/graphene cell is approximately 2.5 times than that of pure P25 cell. PMID- 27658374 TI - Cadm3 (Necl-1) interferes with the activation of the PI3 kinase/Akt signaling cascade and inhibits Schwann cell myelination in vitro. AB - Axo-glial interactions are critical for myelination and the domain organization of myelinated fibers. Cell adhesion molecules belonging to the Cadm family, and in particular Cadm3 (axonal) and its heterophilic binding partner Cadm4 (Schwann cell), mediate these interactions along the internode. Using targeted shRNA mediated knockdown, we show that the removal of axonal Cadm3 promotes Schwann cell myelination in the in vitro DRG neuron/Schwann cell myelinating system. Conversely, over-expressing Cadm3 on the surface of DRG neuron axons results in an almost complete inability by Schwann cells to form myelin segments. Axons of superior cervical ganglion (SCG) neurons, which do not normally support the formation of myelin segments by Schwann cells, express higher levels of Cadm3 compared to DRG neurons. Knocking down Cadm3 in SCG neurons promotes myelination. Finally, the extracellular domain of Cadm3 interferes in a dose-dependent manner with the activation of ErbB3 and of the pro-myelinating PI3K/Akt pathway, but does not interfere with the activation of the Mek/Erk1/2 pathway. While not in direct contradiction, these in vitro results shed lights on the apparent lack of phenotype that was reported from in vivo studies of Cadm3-/- mice. Our results suggest that Cadm3 may act as a negative regulator of PNS myelination, potentially through the selective regulation of the signaling cascades activated in Schwann cells by axonal contact, and in particular by type III Nrg-1. Further analyses of peripheral nerves in the Cadm-/- mice will be needed to determine the exact role of axonal Cadm3 in PNS myelination. GLIA 2016;64:2247-2262. PMID- 27658376 TI - Recovery of ergosterol from the medicinal mushroom, Ganoderma tsugae var. Janniae, with a molecularly imprinted polymer derived from a cleavable monomer template composite. AB - A semi-covalent imprinting strategy has been developed for the synthesis of molecularly-imprinted polymers specific for the fungal sterol, ergosterol, a biological precursor of vitamin D2. This imprinting approach involved a novel post-synthesis cleavable monomer-template composite, namely ergosteryl methacrylate, and resulted in the formation of an imprinted polymer that selectively and efficiently recognized ergosterol through non-covalent interactions. The derived molecularly-imprinted polymer and the corresponding non imprinted polymer were systematically evaluated for their selectivity towards ergosterol via static and dynamic binding studies using various ergosteryl esters (e.g. ergosteryl-cinnamate, -ferulate, -coumarate, -ferulate acetate and acetate, respectively) as competitors. Moreover, the binding capacity of the molecularly imprinted polymer for ergosterol was enhanced when the sample loading conditions involved the use of partially aqueous solvent mixtures, such as acetonitrile/water (9:1 (v/v) or 8:2 (v/v)). These attributes were exploited in a solid-phase extraction format, whereby ergosterol was obtained with excellent recoveries from an extract of the fruiting body powder of the medicinal fungus Ganoderma tsugae var. Janniae. PMID- 27658377 TI - Maximizing performance in supercritical fluid chromatography using low-density mobile phases. AB - The performance of a 3.0mm*150mm column packed with 1.8MUm fully porous HSS-SB C18 particles was investigated in supercritical fluid chromatography (SFC) with low-density, highly expansible carbon dioxide. These conditions are selected for the analysis of semi-volatile compounds. Elevated temperatures (>100 degrees C) were then combined with low column back pressures (<100bar). In this work, the inlet temperature of pure carbon dioxide was set at 107 degrees C, the active back pressure regulator (ABPR) pressure was fixed at 100bar, and the flow rate was set at 2.1mL/min at 12 degrees C (liquefied carbon dioxide) and at an inlet column pressure close to 300bar. Nine n-alkylbenzenes (from benzene to octadecylbenzene) were injected under linear (no sample overload) conditions. The severe steepness of the temperature gradients across the column diameter were predicted from a simplified heat transfer model. Such conditions dramatically lower the column performance by affecting the symmetry of the peak shape. In order to cope with this problem, three different approaches were experimentally tested. They include (1) the decoupling and the proper selection of the inlet eluent temperature with respect to the oven temperature, (2) the partial thermal insulation of the column using polyethylene aerogel, and (3) the application of a high vacuum (10-5Torr provided by a turbo-molecular pump) in a housing chamber surrounding the whole column body. The results reveal that (1) the column efficiency can be maximized by properly selecting the difference between the eluent and the oven temperatures, (2) the mere wrapping of the column with an excellent insulating material is insufficient to fully eliminate heat exchanges by conduction and the undesirable radial density gradients across the column i.d., and (3) the complete thermal insulation of the SFC column under high vacuum allows to maximize the column efficiency by maintaining the integrity of the peak shape. PMID- 27658378 TI - Selective pressurized liquid extraction for the analysis of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and dibenzofurans in soil. AB - During this study a high throughout selective pressurized liquid extraction (SPLE) method was developed and validated for the simultaneous extraction of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/PCDFs) and polychlorinated biphenyls (PCBs) from soil. To that end, extraction rates of PCBs from soil utilizing different extraction solvents and different extraction temperatures were investigated whereas extraction rates were comparable for toluene, n-hexane and dichloromethane (extraction conditions for all utilized solvents: 33mL PLE extraction cell, extraction temperature: 110 degrees C, static extraction time: 5min, flush volume: 60%, purge 90s). Ratios of native PCBs and PCDD/PCDFs congener concentrations after Soxhlet and selective pressurized liquid extraction (SPLE) showed that SPLE is an alternative sample preparation step for the simultaneous determination of PCDD/PCDFs and PCBs in soil. Additional clean-up steps for the separation of PCBs and PCDD/PCDFs utilizing alumina were performed in order to avoid interferences between the component classes. PMID- 27658379 TI - Downstream valorization and comprehensive two-dimensional liquid chromatography based chemical characterization of bioactives from black chokeberries (Aronia melanocarpa) pomace. AB - In this work, a new alternative for the downstream processing and valorization of black chokeberry pomace (Aronia melanocarpa) which could be potentially coupled to a biorefinery process is proposed. This alternative is based on the application of pressurized liquid extraction (PLE) to the residue obtained after the supercritical fluid extraction of the berry pomace. An experimental design is employed to study and optimize the most relevant extraction conditions in order to attain extracts with high extraction yields, total phenols content and antioxidant activity. Moreover, the PLE extracts were characterized by using a new method based on the application of comprehensive two-dimensional liquid chromatography in order to correlate their activity with their chemical composition. Thanks to the use of this powerful analytical tool, 61 compounds could be separated being possible the tentative identification of different anthocyanins, proanthocyanidins, flavonoids and phenolic acids. By using the optimized PLE approach (using pressurized 46% ethanol in water at 165 degrees C containing 1.8% formic acid), extracts with high total phenols content (236.6mg GAE g-1 extract) and high antioxidant activities (4.35mmol TE g-1 extract and EC50 5.92MUgmL-1) could be obtained with high yields (72.5%). PMID- 27658380 TI - Carbon nanotube composite microspheres as a highly efficient solid-phase microextraction coating for sensitive determination of phthalate acid esters in water samples. AB - Multiwalled carbon nanotubes (MWCNTs) on polystyrene (PS) microspheres have been designed and prepared by layer-by-layer assembly via electrostatic interaction. MWCNTs@PS was characterized by scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The new materials were employed as a novel solid-phase microextraction (SPME) coating to enrich trace level of phthalate acid esters (PAEs) in water samples. Five PAEs, di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl adipate (DEHA), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP), were studied in this work. The Box-Behnken design was applied to calculate optimum extraction factors affecting the extraction efficiency using a response surface. In the optimized conditions, the developed technique achieved high enrichment factors (738-2347), low limits of detection (0.0012-0.018MUgL-1) and wide linearity (0.001-5MUgL-1) for detecting PAEs. The method was successfully applied to analyze PAEs in real environmental water samples with recovery ranging from 73.4% to 103.8%. The results demonstrated that MWCNTs@PS are a promising coating material in the SPME of PAEs at trace levels from environmental samples. PMID- 27658381 TI - The chromatography of poly(phenylene ether) on a porous graphitic carbon sorbent. AB - A Porous Graphitic Carbon (PGC) column was evaluated for the analysis of poly(phenylene ether) (PPE). This column appears particularly well-suited for the separation of this polymer. Conditions for the elution of PPE either in adsorption mode with chloroform or size exclusion with 1,2,4-trichlorobenzene (TCB) as eluent were established. Elution of homologous species is obtained in chloroform that follows Martin's rule. A separation based on a gradient consisting of a sequence of non-solvent (acetonitrile), solvent/adsorli (chloroform) provided the highest peak capacity. In TCB, it is possible to obtain rapid size-based separation: with a flow rate of 0.7ml/min, the run time is less than two minutes for a series of polystyrene standards. The PGC column performs remarkably well in this mode and may be a viable solution when a short analysis time is critical such as in a combinatorial laboratory or in a two-dimensional chromatograph. In addition to its value as a sorbent for polymer separation, this column also deserves the attention of the materials engineer. Indeed, the PGC sorbent can be used as a model to probe the interaction between polymers and graphitic fillers such as carbon nanotubes or graphite nanosheets. PMID- 27658382 TI - Development and performance evaluation of a recombinase polymerase amplification assay for the rapid detection of group B streptococcus. AB - BACKGROUND: Despite the implementation of prevention guidelines, group B Streptococcal (GBS) infection remains a leading cause of sepsis, pneumonia, and meningitis, resulting in significant neonatal morbidity and mortality. Preventive approaches that identify women at risk of transmitting GBS have reduced the incidence of neonatal GBS disease, and dramatically decreased the associated mortality rates. However, there is an on-going requirement for a near-patient diagnostic test for GBS that can be carried out at the time of delivery, ideally in the labour ward setting, particularly for women of unknown GBS colonisation status at the time of delivery. METHODS: In this study, a Recombinase Polymerase Amplification (RPA) assay was developed and performance evaluated for the detection of group B Streptococcus in vaginal swabs. The assay uses the cAMP factor (cfb) gene of GBS as the target gene. The analytical performance of the assay was evaluated by testing a panel of GBS reference strains and clinical isolates, and non-GBS organisms. The limit of detection was determined and the clinical performance was evaluated by testing 124 vaginal swabs from women with both GBS positive and negative status. RESULTS: Based on specificity testing carried out the assay was shown to be specific for the target of interest. The limit of detection of the assay was shown to be between six and 12 genome copies and was comparable to that of a real-time PCR assay, both achieving a limit of detection below 12.5 genome copies. The performance of both assays when applied to clinical samples was identical. CONCLUSION: A specific, sensitive RPA assay for GBS was developed. The performance of the assay for testing of clinical samples is within the acceptable range. PMID- 27658383 TI - Molecular evolution and population genetics of a Gram-negative binding protein gene in the malaria vector Anopheles gambiae (sensu lato). AB - BACKGROUND: Clarifying the role of the innate immune system of the malaria vector Anopheles gambiae is a potential way to block the development of the Plasmodium parasites. Pathogen recognition is the first step of innate immune response, where pattern recognition proteins like GNBPs play a central role. RESULTS: We analysed 70 sequences of the protein coding gene GNBPB2 from two species, Anopheles gambiae (s.s.) and An. coluzzii, collected in six African countries. We detected 135 segregating sites defining 63 distinct haplotypes and 30 proteins. Mean nucleotide diversity (pi) was 0.014 for both species. We found no significant genetic differentiation between species, but a significant positive correlation between genetic differentiation and geographical distance among populations. CONCLUSIONS: Species status seems to contribute less for the molecular differentiation in GNBPB2 than geographical region in the African continent (West and East). Purifying selection was found to be the most common form of selection, as in many other immunity-related genes. Diversifying selection may be also operating in the GNBPB2 gene. PMID- 27658385 TI - MRI utility in the detection of disease activity in clinically stable patients with multiple sclerosis: a retrospective analysis of a community based cohort. AB - BACKGROUND: Since the application of MRI scanning to the diagnosis and treatment of multiple sclerosis, it has been recognized that only a small fraction of lesions seen on MRI scans produce recognizable symptoms or neurological findings. Because new lesions may occur without clinical detection, the recommendation has been made that MRI scanning be performed on a routine scheduled basis, usually yearly, even in patients who are clinically stable. METHODS: A retrospective chart review study was conducted on MS patients who had MRI scans of the central nervous system between 2009 and 2012 at Providence Multiple Sclerosis Center. Inclusion criteria were patients with relapsing MS who had been treated with interferon beta or glatiramer acetate for 6 months or longer. Information on type, indication, and result of MRI and whether a change in disease modifying therapy occurred as a result of the scan was collected. RESULTS: Of the 436 clinically stable patients who had routine MRI, 16.7 % of subjects had scans revealing new, enlarged or active lesions, yet in only 4.4 % patients was there a change in therapy based upon MRI results. Subjects who had MRI changes were found to be younger (50.15 vs 53.43, p = 0.02) but there was no significant difference in other demographic or clinical characteristics when compared with the subjects who did not have MRI changes. Thirty-six percent of patients with MRI changes did not change DMT due to patient request. CONCLUSIONS: This study provides data on the likelihood of detecting MRI-documented disease activity, in patients demonstrating longer term sustained clinical stability while receiving DMTs. These results may materially assist in the decision whether or not to perform yearly MRI scanning of such patients. The potential clinical impact of the results of routine MRI scanning must be weighed against the consideration of considerable expense of frequent MRI scanning, and the yet unknown adverse impact of retained gadolinium in patients repeatedly receiving this contrast agent. The long-term clinical impact of not changing DMTs in patients in whom MRI changes were observed will be addressed in future studies of this cohort. PMID- 27658384 TI - The association between dog walking, physical activity and owner's perceptions of safety: cross-sectional evidence from the US and Australia. AB - BACKGROUND: We examined the relationship between dog walking and physical activity within and between four US cities and Australia and investigated if dog walking is associated with higher perceived safety in US and Australian cities. METHODS: Dog owners (n = 1113) in the Pet Connections Study completed a cross sectional survey. Data were collected across four study sites; three in the US (San Diego, Nashville, Portland) and a fourth in Australia (Perth). Physical activity, local walking, dog walking, and individual and community perceptions of safety were analysed for dog walkers and non-dog walkers for each study site. Between-city comparisons were examined for dog walkers. RESULTS: Across all study sites, dog walkers walked with their dog 5-6 times/week for a total of 93-109 min/week and achieved >=30mins of physical activity on more days/week and walked in their neighbourhood more often/week, compared with non-dog walkers (all p <= 0.01). Compared with Perth, significantly fewer dog walkers walked in their local park in the three US study sites. San Diego dog walkers walked more often in their neighborhood/week compared with Perth dog walkers (all p <= 0.05). In Portland, dog walkers perceived significantly more neighborhood problems and in Nashville dog walkers perceived a significantly higher level of neighborhood natural surveillance (i.e., 'eyes on the street'), compared with non-dog walkers (both p <= 0.05). Among dog walkers, females were more likely than males to feel safer walking with their dog in their neighborhood (OR = 2.49; 95 % CI = 1.76, 3.53). Compared with dog walkers in Perth, dog walkers from each of the US study sites felt safer in their neighborhood and perceived there was more neighborhood surveillance (all p <= 0.001). CONCLUSION: This multi-site international study provides further support for the potential for dog walking to increase levels of daily physical activity. Walking with a dog may be a mechanism for increasing perceptions of neighborhood safety and getting to know the neighborhood, however significant between-country differences exist. Further international research is required to understand the drivers for these between-country differences. Community based programs and policies aimed at improving safety and social connectedness should consider the wider community benefits of dog walking and include strategies for supporting more dog walking. PMID- 27658386 TI - Mifepristone combined with ethacridine lactate for the second-trimester pregnancy termination in women with placenta previa and/or prior cesarean deliveries. AB - PURPOSE: This study was aimed to evaluate the safety and efficacy of the second trimester medical abortions using mifepristone and ethacridine lactate in women with placenta previa and/or prior cesarean deliveries. METHODS: The patients who underwent a second-trimester pregnancy termination from January 2009 to December 2015 were retrospectively analyzed. The eligible patients were assigned to four groups based on placentation and cesarean history. The abortion interval (AI), blood loss, hospital stays, incidence of curettage, and transfusion were reviewed. RESULTS: Two women underwent cesarean sections for placenta increta. Finally, 443 patients were enrolled in this study, including 92 with placenta previa, 153 with prior cesarean deliveries, 36 with the both factors, and 236 with normal placentation and no cesarean delivery history. All the included cases had a successful vaginal delivery. There was no significant difference in AI, hospital stay, rate of hemorrhage, and transfusion among the four groups. Patients with prior cesarean section had higher blood loss than the normal group (P = 0.0017), as well as patients with both placenta previa and prior cesarean (P = 0.0018). However, there was no obvious blood loss in patients with placenta previa when compared with normal placetal patients (P = 0.23). No uterine rupture occurred in all patients. CONCLUSIONS: Mifepristone combined with ethacridine lactate is safe and effective for patients with low placentation or/and prior cesarean in the second-trimester pregnancy termination. PMID- 27658387 TI - Is the distribution of care quality provided under pay-for-performance equitable? Evidence from the Advancing Quality programme in England. AB - BACKGROUND: The limited number of existing previous studies of the distribution of quality under NHS Pay-for-performance (P4P) by income deprivation have not analysed the relationship at the individual level and have been restricted to assessing P4P in the primary care setting. In this study, we set out to examine how achievement of P4P 'quality measures' for which NHS hospitals were paid was distributed by income deprivation. METHODS: Design: Retrospective analysis of performance data reported by hospitals, examining how the probability of receiving 23 indicators varied by patients' area deprivation using logistic regression controlling for age and gender. SAMPLE: We use anonymised observational data on 73,002 patients admitted to hospitals in the North West of England between October 2008 and March 2010 for the following five reasons: acute myocardial infarction; coronary artery bypass grafting; heart failure; hip and knee replacement; and pneumonia. RESULTS: The relationship between quality and deprivation varies depending on the point of delivery in the treatment pathway, and on whether delivered for conditions in scheduled or unscheduled care. For diagnostic tests on arrival, receipt of quality was: pro-rich in scheduled care and pro-poor in unscheduled care. Receipt of quality was pro-poor for pre-surgery measures in scheduled care. Receipt of quality at discharge was pro-rich. CONCLUSION: Unlike in primary care, in secondary care quality is not systemically distributed by income deprivation under P4P. Whilst improvements in health inequalities are important system objectives; they may not necessarily be achieved by the adoption of P4P schemes in hospitals. PMID- 27658389 TI - Survey of Medical Oncology Status in Korea (SOMOS-K): A National Survey of Medical Oncologists in the Korean Association for Clinical Oncology (KACO). AB - PURPOSE: This study was conducted to investigate the current role of medical oncologists in cancer care with a focus on increasing the recognition of medical oncology as an independent specialty. MATERIALS AND METHODS: Questionnaires modified from the Medical Oncology Status in Europe Survey dealing with oncology structure, resources, research, and patterns of care given by medical oncologists were selected. Several modifications were made to the questionnaire after feedback from the insurance and policy committee of the Korean Association for Clinical Oncology (KACO). The online survey was then sent to KACO members. RESULTS: A total of 214 medical oncologists (45.8% of the total inquiries), including 71 directors of medical oncology institutions, took the survey. Most institutions had various resources, including a medical oncology department (94.1%) and a department of radiation oncology (82.4%). There was an average of four medical oncologists at each institution. Medical oncologists were involved in various treatments from diagnosis to end-of-life care. They were also chemotherapy providers from a wide range of institutions that treated many types of solid cancers. In addition, 86.2% of the institutions conducted research. CONCLUSION: This is the first national survey in Korea to show that medical oncologists are involved in a wide range of cancer treatments and care. This survey emphasizes the contributions and proper roles of medical oncologists in the evolving health care environment in Korea. PMID- 27658388 TI - Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea. AB - PURPOSE: This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea. MATERIALS AND METHODS: In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data. RESULTS: Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, -2.01%; p=0.05) and bladder (APC, 0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (-7.20%). CONCLUSION: The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers. PMID- 27658390 TI - Clinically Significant Unclassified Variants in BRCA1 and BRCA2 genes among Korean Breast Cancer Patients. AB - PURPOSE: Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls. MATERIALS AND METHODS: A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico. RESULTS: Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function. CONCLUSION: This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families. PMID- 27658391 TI - Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL. AB - BACKGROUND: GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). METHODS: We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium(r) HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3low and GATA3high expressing T-ALL patients. In addition, the ETP-ALL cell line PER-117 was investigated for cytotoxicity, apoptosis, GATA3 mRNA expression, DNA methylation, and global gene expression before and after treatment with decitabine. RESULTS: In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3low. DNA methylation analysis revealed a high degree of GATA3 CpG island methylation in GATA3low compared with GATA3high ETP-ALL patients (mean 46 vs. 21 %, p < 0.0001). Genome-wide expression profiling of GATA3low ETP-ALL exhibited enrichment of myeloid/lymphoid progenitor (MLP) and granulocyte/monocyte progenitor (GMP) genes, while T cell-specific signatures were downregulated compared to GATA3high ETP-ALL. Among others, FLT3 expression was upregulated and mutational analyses demonstrated a high rate (79 %) of FLT3 mutations. Hypomethylating agents induced reversal of GATA3 silencing, and gene expression profiling revealed downregulation of hematopoietic stem cell genes and upregulation of T cell differentiation. CONCLUSIONS: We propose GATA3low ETP-ALL as a novel stem cell like leukemia with implications for the use of myeloid-derived therapies. PMID- 27658392 TI - Ubiquitin Ligase COP1 Controls Hepatic Fat Metabolism by Targeting ATGL for Degradation. AB - Optimal control of hepatic lipid metabolism is critical for organismal metabolic fitness. In liver, adipose triglyceride lipase (ATGL) serves as a major triacylglycerol (TAG) lipase and controls the bulk of intracellular lipid turnover. However, regulation of ATGL expression and its functional implications in hepatic lipid metabolism, particularly in the context of fatty liver disease, is unclear. We show that E3 ubiquitin ligase COP1 (also known as RFWD2) binds to the consensus VP motif of ATGL and targets it for proteasomal degradation by K-48 linked polyubiquitination, predominantly at the lysine 100 residue. COP1 thus serves as a critical regulator of hepatocyte TAG content, fatty acid mobilization, and oxidation. Moreover, COP1-mediated regulation of hepatic lipid metabolism requires optimum ATGL expression for its metabolic outcome. In vivo, adenovirus-mediated depletion of COP1 ameliorates high-fat diet-induced steatosis in mouse liver and improves liver function. Our study thus provides new insights into the regulation of hepatic lipid metabolism by the ubiquitin-proteasome system and suggests COP1 as a potential therapeutic target for nonalcoholic fatty liver disease. PMID- 27658395 TI - Ca2+ Ultrastructural Distribution in Root Apical Cells of Wheat Under Aluminum Stress. PMID- 27658393 TI - [Emotion regulation and pain : Behavioral and neuronal correlates: a transdiagnostic approach]. AB - Emotions and emotion regulation are of special importance in the perception and modulation of pain but the mechanisms underlying this reciprocal relationship remain unclear. The transdiagnostic model provides an approach to explain the link between pain and emotion regarding cognitive and neuronal mechanisms and aims to identify mutual processes, which are relevant for both. Structural and functional imaging studies of pain indicate the involvement of specific cortical and subcortical structures, which also play an important role in emotion regulation. While numerous studies have investigated emotion regulation and their correlates in the central nervous system in pathological states, the research on emotion regulation in pain is still young. The purpose of this review is to provide an overview of experimental and clinical studies of neuronal and behavioral correlates of pain-related emotion regulation. The current transdiagnostic approach may be able to enhance pain relief in the future. PMID- 27658394 TI - Functionally aberrant dendritic cell subsets and expression of DC-SIGN differentiate acute from chronic HBV infection. AB - BACKGROUND: Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs). AIMS AND OBJECTIVES: We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection. METHODS: We measured the frequencies of circulating myeloid (mDC) and plasmacytoid (pDC) dendritic cells and IFN-alpha production along with the expression of DC-SIGN and Toll Like Receptors (TLR's) in HBV patients at different time points. Also investigated in healthy volunteers, the dynamic changes in TLRs expression after receiving hepatitis B vaccine. RESULTS: On follow-up of AVHB patients, we found the mDC population was significantly higher at week 4 and 6 (p < 0.02, 0.01), whereas the pDC population was unchanged at week 6 compared with week 0. Whereas frequencies of mDCs and pDCs were found to be elevated in AVHB and CHB patients than HC (p < 0.00 and 0.01, respectively) but was comparable among AVHB vs CHB. The DCs in CHB patients were functionally impaired with significantly low IFN-alpha production and low DCSIGN expression (p < 0.04 and 0.00, respectively). Even after stimulation by TLR agonists, no change was found in IFN-alpha production in CHB patients. MyD88 and IL-6, IFN-alpha mRNA levels were also found down-regulated. Interestingly, on follow-up after HBV vaccine, TLRs expression was found high at day 3 after vaccination. DISCUSSION: The initial events of immune activation might be responsible for modulating immune response. These novel observations would pave the way for the development of antiviral strategies for chronic HBV infection. PMID- 27658396 TI - Effects of slice orientation on reproducibility of sequential assessment of right ventricular volumes and ejection fraction: short-axis vs transverse SSFP cine cardiovascular magnetic resonance. AB - BACKGROUND: Test-retest reproducibility is of utmost importance in follow-up of right ventricular (RV) volumes and function; optimal slice orientation though is not yet known. We compared test-retest reproducibility and intra-/inter-observer variability of right ventricular (RV) volumes and function assessed with short axis and transverse cardiovascular magnetic resonance (CMR). METHODS: Eighteen volunteers underwent cine CMR for RV assessment obtaining ventricular coverage in short-axis and transverse slice orientation. Additional 2D phase contrast flow imaging of the main pulmonary artery (MPA) was performed. After complete repositioning repeat acquisitions were performed. Data sets were contoured by two blinded observers. Statistical analysis included Student's t-test, Bland-Altman plots, intra-class correlation coefficient (ICC) and 2-way ANOVA, SEM and minimal detectable difference calculations. RESULTS: Heart rates (65.0 +/- 7.4 vs. 67.6 +/- 9.9 bpm; P = 0.1) and MPA flow (89.8 +/- 16.6 vs. 87.2 +/- 14.9 mL; P = 0.1) did not differ between imaging sessions. EDV and ESV demonstrated an inter-study bias of 0.4 %[-9.5 %,10.3 %] and 2.1 %[-12.3 %,16.4 %] for short-axis and 1.1 %[ 7.3 %,9.4 %] and 0.8 %[-16.0 %,17.6 %] for transverse orientation, respectively. There was no significant interaction between imaging orientation and interstudy reproducibility (p = 0.395-0.824), intra-observer variability (p = 0.726-0.862) or inter-observer variability (p = 0.447-0.706) by 2-way ANOVA. Inter-observer agreement by ICC was greater for short axis versus transverse orientation for all parameters (0.769-0.986 vs. 0.625-0.983, respectively). Minimal detectable differences for short axis and transverse orientations were 10.1 mL/11.5 mL for EDV, 8.3 mL/8.4 mL for ESV and 4.1 % vs. 4.7 % for EF, respectively. CONCLUSION: Short-axis and transverse orientation both provide reliable and reproducible measures for follow-up of RV volumes and global function. Therefore, additional transverse SSFP cine CMR may not necessarily be required if performed for the sole purpose of quantitative volumetric RV assessment. PMID- 27658397 TI - Internalization of a novel, huge lectin from Ibacus novemdentatus (slipper lobster) induces apoptosis of mammalian cancer cells. AB - An N-acetyl sugar-binding lectin (termed iNoL) displaying cytotoxic activity against human cancer cells was isolated from the slipper lobster Ibacus novemdentatus (family Scyllaridae). iNoL recognized monosaccharides containing N acetyl group, and glycoproteins (e.g., BSM) containing oligosaccharides with N acetyl sugar. iNoL was composed of five subunits (330, 260, 200, 140, and 30 kDa), which in turn consisted of 70-, 40-, and 30-kDa polypeptides held together by disulfide bonds. Electron microscopic observations and gel permeation chromatography indicated that iNoL was a huge (500-kDa) molecule and had a polygonal structure under physiological conditions. iNoL displayed cytotoxic (apoptotic) effects against human cancer cell lines MCF7 and T47D (breast), HeLa (ovarian), and Caco2 (colonic), through incorporation (internalization) into cells. The lectin was transported into lysosomes via endosomes. Its cytotoxic effect and incorporation into cells were inhibited by the co-presence of N-acetyl D-mannosamine (ManNAc). Treatment of HeLa cells with iNoL resulted in DNA fragmentation and chromatin condensation, through activation of caspase-9 and -3. In summary, the novel crustacean lectin iNoL is incorporated into mammalian cancer cells through glycoconjugate interaction, and has cytotoxic (apoptotic) effects. PMID- 27658399 TI - Cu and Zr surface sites in the photocatalytic activity of TiO2 nanoparticles. AB - The rate of methylene blue and terephthalic acid degradation assisted with double metal-modified catalyst (0.1 mol% Cu and 1.0 mol% Zr) was enhanced as compared with single metal-modified catalysts (0.1, 0.5 mol% Cu and 1.0 mol% Zr). The wet impregnation method was used for copper and zirconium modification of the surface of Aeroxide P25 TiO2 particles. Simultaneous loading of both metals on the surface of P25 leads to an increased specific surface area of the obtained material despite negative Cu influence. The tendency of stabilization and agglomerate size rising with the time for Cu and Zr-modified catalysts were traced by dynamic light scattering (DLS) measurements. The observed optical characteristics suggest that Cu compensated the broadening of band gap caused by Zr loading. Crystal structure of obtained photocatalysts was explored by XRD; morphological data and particle size were obtained by SEM. EDX was used for Zr and Cu content determination. Cu K-edge extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES) analytical techniques were used to investigate the local Cu neighbourhood in the samples and to identify copper coordination and valence state of copper species in the synthesized nanocomposites. PMID- 27658398 TI - Stereoselective toxicity of etoxazole to MCF-7 cells and its dissipation behavior in citrus and soil. AB - The stereoselective cytotoxicity of new chiral acaricide etoxazole and its dissipation in citrus and soil were investigated for the first time. Enantioselective toxicity and oxidative stress of etoxazole toward MCF-7 cells was conducted. The phenomenon of dose- and form-dependent cytotoxicity was demonstrated by MTT and LDH assays, ROS generation, and SOD and CAT activity alternation. Cytotoxicity ranks were found to be consistent with oxidative damage as (R)- > Rac- > (S)-etoxazole. Moreover, the results of enantioselective degradation showed that (S)-etoxazole degraded faster than its antipode (R) etoxazole. The gradual raise of EF values indicated the achievement of enantioselective degradation in citrus and soil, leaving the enrichment of (R) etoxazole isomer. Significant differences of environmental behavior and cytotoxicity of etoxazole enantiomers were found in this study which provided valuable insight into the mechanism of potential toxicity and warranted more careful assessment of this pesticide before its agricultural application. PMID- 27658400 TI - Emissions of microplastic fibers from microfiber fleece during domestic washing. AB - Microplastics are found in marine and freshwater environments; however, their specific sources are not yet well understood. Understanding sources will be of key importance in efforts to reduce emissions into the environment. We examined the emissions of microfibers from domestic washing of a new microfiber polyester fleece textile. Analyzing released fibers collected with a 200 MUm filter during 10 mild, successive washing cycles showed that emission initially decreased and then stabilized at approx. 0.0012 wt%. This value is our estimation for the long term release of fibers during each washing. Use of detergent and softener did not significantly influence emission. Release of fibers during tumble drying was approx. 3.5 times higher than during washing. PMID- 27658401 TI - Evaluation of a spatialized agronomic model in predicting yield and N leaching at the scale of the Seine-Normandie Basin. AB - The EU directive has addressed ambitious targets concerning the quality of water bodies. Predicting water quality as affected by land use and management requires using dynamic agro-hydrogeological models. In this study, an agronomic model (STICS) and a hydrogeological model (MODCOU) have been associated in order to simulate nitrogen fluxes in the Seine-Normandie Basin, which is affected by nitrate pollution of groundwater due to intensive farming systems. This modeling platform was used to predict and understand the spatial and temporal evolution of water quality over the 1971-2013 period. A quality assurance protocol (Refsgaard et al. Environ Model Softw 20: 1201-1215, 2005) was used to qualify the reliability of STICS outputs. Four iterative runs of the model were carried out with improved parameterization of soils and crop management without any change in the model. Improving model inputs changed much more the spatial distribution of simulated N losses than their mean values. STICS slightly underestimated the crop yields compared to the observed values at the administrative district scale. The platform also slightly underestimated the nitrate concentration at the outlet level with a mean difference ranging from -1.4 to -9.2 mg NO3 L-1 according to the aquifer during the last decade. This outcome should help the stakeholders in decision-making to prevent nitrate pollution and provide new specifications for STICS development. PMID- 27658402 TI - EDTA and hydrochloric acid effects on mercury accumulation by Lupinus albus. AB - The efficiency of white lupine (Lupinus albus) to uptake and accumulate mercury from a soil polluted by mining activities was assessed in a pot experiment with chemically assisted phytoextraction. The mobilizing agents tested were ethylenediaminetetracetic acid (EDTA) and hydrochloric acid (HCl). Two doses of each amendment were used (0.5 and 1.0 g of amendment per kg of soil), and unamended pots were used as a control. Addition of HCl to the soil did not negatively affect plant biomass, while the use of EDTA led to a significant decrease in plant growth when compared to that found for non-treated pots, with plants visually showing symptoms of toxicity. The addition of hydrochloric acid increased root, shoot and total plant Hg uptake of white lupine by 3.7 times, 3.1 times and 3.5 times, respectively, in relation to non-amended plants. The greatest efficiency was obtained for the highest HCl dose. EDTA led to higher concentrations of total plant Hg than that found with the control, but, due to the aforementioned decrease in plant biomass, the Hg phytoextraction yield was not significantly increased. These results were attributed to the capability of both amendments to form stable Hg complexes. The concentration of Hg in the water of the soil pores after the phytoextraction experiment was very low for all treatments, showing that risks derived from metal leaching could be partially avoided by using doses and chemicals suitable to the concentration of metal in the soil and plant performance. PMID- 27658403 TI - N-fixing trees in wetland restoration plantings: effects on nitrogensupply and soil microbial communities. AB - To investigate the impact of an exotic Frankia nodulated tree (Alnus trabeculosa) on soil nitrogen content, soil microbial composition, and the abundance of N turnover-related functional microorganism community, we compared the community structure and abundance of key functional genes (nifH, bacterial/archaeal amoA, and nosZ) in the rhizosphere and nonrhizosphere of monoculture of Phragmites australis and A.trabeculosa-P.australis mixed communities by MiSeq Illumina sequencing and real-time PCR, respectively. The introduction of Frankia nodulated tree to recover degraded wetland was effective in the accumulation of soil organic carbon and nitrogen, which was the key factor to impact on the bacterial community composition revealed by canonical correspondence analysis. Acidobacteria and Proteobacteria were the dominant bacterial phylums while seven rare phyla appeared the most phylogenetically different among the investigated soil of two vegetations, including Chlorobi, Cyanobacteria, OD1, OP11, TM6, TM7, and GN02. The gene copy numbers of nifH were ranged from 2.28 * 108 to 2.96 * 109 copies g-1 dry soil in the wetland, and which were significantly higher in soil samples from P. australis than that from A.trabeculosa. While the abundance of nosZ in both rhizosphere and nonrhizosphere soils of A.trabeculosa-P.australis mixed communities was significantly lower compared with P.australis monoculture. The potential nitrification (PNA) (0.15-0.41 mg NOx-N kg-1 dry soil d-1) in the rhizosphere of A. trabeculosa was significantly higher than that of P. australis, and the soil denitrification enzyme activity (DEA) (0.42-0.90 nmol N2O-N g-1 dry soil h-1) was lower in the mixed community compared with monoculture of P. australis. The introduced planting of Frankia nodulated tree effectively accumulated soil organic carbon and nitrogen and reduce the relative abundance and activity of nitrogen-fixing bacteria and denitrification bacteria. PMID- 27658404 TI - Carbon emissions, logistics volume and GDP in China: empirical analysis based on panel data model. AB - This paper studies the relationship among carbon emissions, GDP, and logistics by using a panel data model and a combination of statistics and econometrics theory. The model is based on the historical data of 10 typical provinces and cities in China during 2005-2014. The model in this paper adds the variability of logistics on the basis of previous studies, and this variable is replaced by the freight turnover of the provinces. Carbon emissions are calculated by using the annual consumption of coal, oil, and natural gas. GDP is the gross domestic product. The results showed that the amount of logistics and GDP have a contribution to carbon emissions and the long-term relationships are different between different cities in China, mainly influenced by the difference among development mode, economic structure, and level of logistic development. After the testing of panel model setting, this paper established a variable coefficient model of the panel. The influence of GDP and logistics on carbon emissions is obtained according to the influence factors among the variables. The paper concludes with main findings and provides recommendations toward rational planning of urban sustainable development and environmental protection for China. PMID- 27658405 TI - Heavy metals in the riverbed surface sediment of the Yellow River, China. AB - One hundred and eleven riverbed surface sediment (RSS) samples were collected to determine the heavy metal concentration throughout the Inner Mongolia reach of the Yellow River (IMYR), which has been subjected to rapid economic and industrial development over the past several decades. Comprehensive analysis of heavy metal contamination, including the enrichment factor, geo-accumulation index, contamination factor, pollution load index, risk index, principal component analysis (PCA), hierarchical cluster analysis (HCA), and Pearson correlation analysis, was performed. The results demonstrated that a low ecological risk with a moderate level of heavy metal contamination was present in the IMYR due to the risk index (RI) being less than 150 and the pollution load index (PLI) being above 1, and the averaged concentrations of Co, Cr, Cu, Mn, Ni, Ti, V, and Zn in the RSS, with standard deviations, were 144 +/- 69, 77.91 +/- 39.28, 22.95 +/- 7.67, 596 +/- 151, 28.50 +/- 8.01, 3793 +/- 487, 69.11 +/- 18.44, and 50.19 +/- 19.26 mg kg-1, respectively. PCA, HCA, and Pearson correlation analysis revealed that most of the RSS was heavily contaminated with Zn, Ni, and Cu, due to the influence of anthropogenic activities; moderately contaminated with Ti, Mn, V and Cr because of the dual influence of anthropogenic activities and nature; and slightly to not contaminated with Co because it occurs mainly in the bordering desert areas. Graphic abstract ?. PMID- 27658407 TI - Future of lignite resources: a life cycle analysis. AB - Lignite is a low-quality energy source which accounts for 13 % of China's coal reserves. It is imperative to improve the quality of lignite for large-scale utilization. To further explore and analyze the influence of various key processes on the environment and economic costs, a lignite drying and compression technology is evaluated using an integrated approach of life cycle assessment and life cycle costs. Results showed that lignite mining, direct air emissions, and electricity consumption have most significant impacts on the environment. An integrated evaluation of life cycle assessment and life cycle costs showed that the most significant contributor to the environmental impacts and economic costs was the lignite mining process. The impact of transportation and wastewater treatment process on the environment and economic costs was small enough to be ignored. Critical factors were identified for reducing the environmental and economic impacts of lignite drying and compression technology. These findings provide useful inputs for both industrial practice and policy making for exploitation, processing, and utilization of lignite resources. PMID- 27658406 TI - Effects of nitrogen application rates on net annual global warming potential and greenhouse gas intensity in double-rice cropping systems of the Southern China. AB - The net global warming potential (NGWP) and net greenhouse gas intensity (NGHGI) of double-rice cropping systems are not well documented. We measured the NGWP and NGHGI including soil organic carbon (SOC) change and indirect emissions (IE) from double-crop rice fields with fertilizing systems in Southern China. These experiments with three different nitrogen (N) application rates since 2012 are as follows: 165 kgN ha-1 for early rice and 225 kgN ha-1 for late rice (N1), which was the local N application rates as the control; 135 kgN ha-1 for early rice and 180 kgN ha-1 for late rice (N2, 20 % reduction); and 105 kgN ha-1 for early rice and 135 kgN ha-1 for late rice (N3, 40 % reduction). Results showed that yields increased with the increase of N application rate, but without significant difference between N1 and N2 plots. Annual SOC sequestration rate under N1 was estimated to be 1.15 MgC ha-1 year-1, which was higher than those under other fertilizing systems. Higher N application tended to increase CH4 emissions during the flooded rice season and significantly increased N2O emissions from drained soils during the nonrice season, ranking as N1 > N2 > N3 with significant difference (P < 0.05). Two-year average IE has a huge contribution to GHG emissions mainly coming from the higher N inputs in the double-rice cropping system. Reducing N fertilizer usage can effectively decrease the NGWP and NGHGI in the double-rice cropping system, with the lowest NGHGI obtained in the N2 plot (0.99 kg CO2-eq kg-1 yield year-1). The results suggested that agricultural economic viability and GHG mitigation can be simultaneously achieved by properly reducing N fertilizer application in double-rice cropping systems. PMID- 27658408 TI - Distribution and risk assessment of metals and arsenic contamination in man-made ditch sediments with different land use types. AB - Ditches are subjected to a large input of nutrients, trace metals, and arsenic and the enhancement of sedimentation due to human activities. However, the influence of different types of land uses on the distribution and associated environmental risk of metals and arsenic in the Red purple Sichuan Basin remains largely unclear, which is needed for water management. This study was carried out to characterize metal/metalloid status in ditch sediments from different land uses. A total of 68 surface sediment samples (0-5 cm) were collected from open ditches distributed in different land use types, i.e., cultivated ditches (CD), barren land ditches (BLD), roadside ditches (RSD), and residential ditches (RD), within the Sichuan Basin. Mean concentrations of Cr, Ni, Cu, Zn, Cd, Pb, and Mn in both RD and RSD were above the soil background values of Sichuan Basin, but Cd in ditch sediments of the basin posed considerable ecological risk to the environment. Overall, metals/metalloid (except Pb) decreased in the following order of RD > RSD > BLD > CD. Of the different land use types in the hilly region, residential and roadside land uses were likely to adverse effects on aquatic life. Multivariate statistical analysis showed that Mn, As, Cu, Ni, Zn, Fe, and Al were mainly influenced by natural weathering (erosion), while Pb might come from heavy vehicular traffic. The degree of contamination (Md), enrichment factor (EF), and the geo-accumulation index (Igeo) showed that Cd causes strong sediment pollution in the basin. Sediment quality guidelines SQG-Q values displayed that metals and arsenic created medium-low potential of adverse biological effects. These results provide baseline information on the metals and arsenic pollution in the Sichuan Basin. Awareness of land use type contributions to metals and arsenic requires that these man-made ditches be considered for their mitigation of pollutants in this region. PMID- 27658409 TI - Organochlorine pesticides and polychlorinated biphenyls in surface water around Beijing. AB - Contaminant concentrations, sources, seasonal variation, and eco-toxicological risk of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in surface water around Beijing from summer to winter in 2015 and 2016 were investigated. The concentrations of ?OCPs and ?PCBs ranged from 9.81 to 32.1 ng L 1 (average 15.1 +/- 7.78 ng L-1) and from 7.41 to 54.5 ng L-1 (average 21.3 +/- 1.87 ng L-1), respectively. Hexachlorocyclohexane (HCHs) were the dominated contamination both in aqueous and particulate phase. For PCBs, lower chlorinated PCBs were the major contaminants. Compositions of HCHs, dichlorodiphenyltrichloroethane (DDTs), and PCBs indicated that the sources of OCPs and PCBs in water were due to historical usage in the study areas. For OCPs, there was an obvious variation among three seasons, while insignificant change was shown for PCBs. Water quality standards for China's surface water were not exceeded in this study. Concentrations at Miyun Reservoir, the primary source of drinking water to Beijing, when compared to the USEPA's criterion for cancer risk was below the level of risk. PMID- 27658410 TI - Seasonal and storm-driven changes in chemical composition of dissolved organic matter: a case study of a reservoir and its forested tributaries. AB - Many drinking water supplies are located in forested watersheds, which operate as an important source of dissolved organic matter (DOM). In this study, monthly sampling campaigns were conducted from a reservoir (Daecheong Reservoir, South Korea) and its forested tributaries for five consecutive months (June to October) to examine the variations of DOM composition. Excitation-emission matrix fluorescence spectroscopy combined with parallel factor analysis (EEM-PARAFAC) was applied to track the variations of different fluorescent components within bulk DOM. Selected samples were further separated into hydrophobic (Ho) and hydrophilic (Hi) fractions. Water quality and DOM composition varied greatly with the sampling locations including the upstream and the downstream tributary sites, and the reservoir. Non-metric multidimensional scaling (NMDS) provided the information on the DOM sources and the potential processes leading to the observed DOM changes. Four of the five fluorescent components, identified by EEM PARAFAC, were well correlated with the flow rates of the tributaries, suggesting hydrological control on DOM composition. The greatest effects were found on two terrestrial humic-like components (C1 and C2). The Ho fraction of DOM was more abundant for the post-storm samples versus the non-storm samples, supporting the important roles of hydrology on the changes in chemical composition of DOM. The amounts of the DOM resin fractions, either Ho or Hi, showed strong relationships with C1 and C2, suggesting that DOM fluorescence could be successfully applied to estimate different DOM chemical constituents in forested watersheds. PMID- 27658411 TI - Schwartz Centre Rounds: a new initiative in the undergraduate curriculum-what do medical students think? AB - BACKGROUND: Training to be a doctor and caring for patients are recognized as being stressful and demanding. The wellbeing of healthcare professionals impacts upon the wellbeing and care of patients. Schwartz Centre Rounds (SCRs), multidisciplinary meetings led by a trained facilitator and designed for hospital staff, were introduced to enhance communication and compassion, and have since been widely adopted as a way of fostering compassion. The continuum of education suggests that medical students need to develop these attributes in conjunction with resilience and maintaining empathy. The benefits of SCRs in fostering this development in medical students is unexplored. The objective of this study was to examine the potential of SCRs within the undergraduate curriculum. METHODS: Two student-focused SCRs were piloted at a major medical school. The sessions were based on the current format implemented across the US and UK: a presentation of cases by a multidisciplinary panel followed by an open discussion with the audience. Participants were asked to complete an evaluative questionnaire immediately following the sessions. Seven students took part in a focus group to explore their views on the SCR. Data sets were examined using descriptive statistics and thematic analysis. RESULTS: Feedback was obtained from 77 % (258/334) Year 5 and 37 % (126/343) Year 6 students. Mean student ratings of the session on a five-point scale, where 1 = poor and 5 = exceptional, were 3.5 (Year 5) and 3.3 (Year 6). Over 80 % of respondents either agreed or strongly agreed that the presentation of cases was helpful and gave them insight into how others feel/think about caring for patients. Eighty percent said they would attend a future SCR and 64 % believed SCRs should be integrated into the curriculum. Focus group participants felt SCRs promoted reflection and processing of emotion. Students identified smaller group sizes and timing in the curriculum as ways of improving SCRs. CONCLUSION: Students were positive about SCRs, preferring them to their current reflective practice assignments. Whether this results in sustained benefits to trainee doctors is yet to be explored. Consideration is given to overcoming the challenges that were encountered, such as optimal timing and participation. Staff training and costs are potential obstacles to adoption. PMID- 27658413 TI - Nathaniel Gist Gee's contribution to biology in modern China. PMID- 27658412 TI - Recurrence of giant cell tumour of bone: role of p53, cyclin D1, beta-catenin and Ki67. AB - PURPOSE: To determine various clinical, radiographic, and pathological parameters which may indicate an increased risk of Giant cell tumour of bone (GCTB) recurrence after surgical therapy. METHODS: The study included a total of 164 GCTB samples; 118 (72 %) primary tumours, and 46 (28 %) recurrences; which were analyzed on immunohistochemistry for expression of Ki67, p53, cyclin D1, and beta catenin. RESULTS: Among 13 analyzed clinical, radiological, and histological variables, which presented possible predictive factors for the incidence of GCTB relapse, univariate logistic regression (ULR) extract three highly statistically significant parameters: 1) lesion localization, 2) nuclear p53 expression in mononuclear cells, and 3) nuclear cyclin D1 expression in giant multinuclear cells. The multivariate logistic regression (MLR), revealing that p53 expression in mononuclear cells was the most significant predictive factor (HR = 6,181 p < 0,001), the positivity of which indicated six times higher probability for recurrence in GCTB. The expression of cyclin D1 in giant cells, containing less than 15 nuclei, was also statistically significant (HR = 8,398, p = 0,038) for predicting the recurrence, and demonstrated eight times more frequent recurrence in positive tumours. CONCLUSIONS: This study confirmed independent predicting factors for GCTB reccurence: p53 expression in mononuclear tumour cells and cyclin D1 expression in giant multinuclear cells. Results are new addition to generally known parameters, such as: localization of lesion, number of surgical interventions, clear destruction of cortex with the presence of extracompartmental lesion, and histological criteria for malignancy and can help in further research and treatment of GCTB. PMID- 27658414 TI - Arthroscopic Surgical Technique for an Acute Talar Dome Osteochondral Lesion in a Professional Rugby League Player. AB - BACKGROUND: Talar osteochondral lesions represent challenging clinical entities, particularly in high-demand athletes. Surgical treatment of large lesions often requires a 2-step procedure, or the use of osteotomy in the case of autologous osteochondral transfer, which can delay return to sport. METHODS: A professional rugby league player underwent surgery for a complex injury to the ankle. A talar osteochondral lesion with a maximal diameter of 15 mm was treated in an arthroscopic fashion using the cartilage taken from the completely displaced osteochondral fragment. Cartilage was cut into chips and combined with bone graft product containing platelet-derived growth factor and a porous collagen scaffold. Autologous cartilage was then reimplanted arthroscopically. The patient was allowed full ankle motion from 2 weeks postoperatively, and weightbearing was commenced at 6 weeks. Follow-up imaging and functional outcomes, including return to sport, were assessed at regular intervals. RESULTS: The patient was able to return to professional rugby league by 23 weeks postoperatively. Magnetic resonance imaging at 16 months postoperatively showed restoration of the subchondral plate and osseous infill. At final follow-up, the patient remained pain free and was playing at preinjury level. CONCLUSION: This report describes good outcomes using a novel, 1-step cartilage repair technique to treat a large talar osteochondral lesion in a professional athlete. LEVELS OF EVIDENCE: Level V: Expert opinion. PMID- 27658416 TI - Letter to the Editor: "Risk of venous thromboembolism among patients with vasculitis: a systematic review and meta-analysis". PMID- 27658415 TI - Assessment of serum CX3CL1/fractalkine level in Han Chinese girls with anorexia nervosa and its correlation with nutritional status: a preliminary cross sectional study. AB - The chemokine (C-X3-C motif) ligand 1 (CX3CL1), also named fractalkine (FKN), has been implicated in psychiatric disorders and functions as a novel adipocytokine. However, no attention has been paid to the role of FKN in anorexia nervosa (AN). The current study was performed to explore FKN levels in AN to determine its role in the involvement of AN. A total of 96 girls aged 11-18 years with AN (n=34), healthy controls (HC; n=32) and simple obesity (OB, n=30) were enrolled in the cross-sectional study. Blood samples were collected during the fasting state. Serum FKN concentrations were determined using ELISA. The skinfold thickness (TSF) of the biceps and triceps as well as mid-arm muscle circumference (MAMC) were used to determine the nutritional status. Our results showed that serum FKN levels were significantly lower in the AN group than in the control and OB groups. After adjusting for body mass index (BMI), FKN concentrations in the AN group were statistically higher than in the HC and OB groups. Significant correlations between serum FKN and body weight, BMI, Cole index and serum insulin were observed. In addition, serum FKN levels were positively related to TSF and MAMC in all subjects. Serum FKN concentrations are attenuated in girls with AN compared with healthy adolescents and are positively related to nutritional status. The lower FKN levels may be regulated by nutrition status and response to starvation. After adjusting for BMI, higher FKN levels may reflect that persistent inflammation is present in patients with AN. PMID- 27658417 TI - Optimizing therapy in inflammatory arthritis: prediction of relapse after tapering or stopping treatment for rheumatoid arthritis patients achieving clinical and radiological remission. AB - This study aims to assess clinical, lab/immunological or imaging (joint ultrasonography) markers able to predict disease relapse in RA patients in sustained remission when tapering or stopping their treatment. One hundred fifty seven RA patients in clinical remission (DAS-28 <2.6 for >6 months), receiving treatment with sDMARDs and bDMARD therapy, were randomly allocated into any of five groups: Group 1: continue full dose DMARDs and taper biologic therapy by 50 % (31 patients); Group 2: taper both DMARDs and biologic therapy dose by 50 % (32 patients); Group 3: taper DMARDs by 50 % and stop biologic therapy (31 patients); Group 4: stop both DMARDs and biologic therapy (31 patients); Group 5: continue medications without change (31 patients). Forty joints were assessed ultrasonographically (DAS-28 joints + ankles + metatarsophalangeal joints) and prospectively monitored for 12 months. The primary endpoint was sustained remission for 12 months. Patients were considered as having a relapse when the DAS-28 score was >3.2 and anti-rheumatic treatment was escalated. The frequency of relapse was 41.9 % in Group 1, 59.3 % in Group 2, 67.7 % in Group 3, 77.4 % in Group 4 and 6.5 % in Group 5. Relapse rates were significantly higher in patients whose ultrasound scores raised within 3 months of stopping their medications (P < 0.001 for both GS and PD scores). Cox regression identified ACPA positivity (at baseline) and progression of functional disability (at 2 months) as predictors for relapse. Tapering therapy is feasible in RA patients. Tailored dynamic approach is advised. Joint ultrasonographic assessment, ACPA positivity and worsening functional disability predicted relapse within a short term after discontinuation of the treatment. RA patients whose DAS-28 score was <2 were more likely to remain in remission. PMID- 27658418 TI - Risk of acute gout among active smokers: data from nationwide inpatient sample. AB - Smoking has been found to be negatively correlated with serum uric acid levels by virtue of reduced production and increased consumption of endogenous antioxidant uric acid among smokers and has been reported to decrease incidence of gout. To shed further light on the question of association between active smoking and acute gout by examining this association using a large inpatient US database, using the Nationwide Inpatient Sample data from 2009 to 2011, we identified current smokers based on the International Classification of Diseases, Ninth Revision (ICD-9) code 305.1 and were assumed to have ceased smoking during hospital stay. Patients who developed acute gout inhospital were identified based on ICD-9 code 274.01 at secondary diagnosis position. Univariate and multivariate logistic regressions were used to derive odds ratio for measures of association. Statistical analysis was done using STATA version 13.0 (College Station, TX). A total of 17,847,045 discharge records were used which included 13,932 (0.08 %) inhospital acute gouty arthritis and 2,615,944 (14.66 %) active smokers. Both univariate (OR 0.59, CI 0.54-0.63, p < 0.0001) and multivariate (OR 0.64, CI 0.59 0.68, p < 0.0001) regressions showed statistically significant reduction of acute gout among hospitalized patients who were current smokers but were assumed to have ceased smoking during hospital stay. Active tobacco use was associated with a lower risk of acute inpatient gouty arthritis, even when controlling for conventional risk factors. More study is needed to correlate this finding with uric acid levels, and a better understanding of the mechanisms that explain this finding are necessary. PMID- 27658420 TI - Like prions: the propagation of aggregated tau and alpha-synuclein in neurodegeneration. AB - The abnormal aggregation of a small number of known proteins underlies the most common human neurodegenerative diseases. In tauopathies and synucleinopathies, the normally soluble intracellular proteins tau and alpha-synuclein become insoluble and filamentous. In recent years, non-cell autonomous mechanisms of aggregate formation have come to the fore, suggesting that nucleation-dependent aggregation may occur in a localized fashion in human tauopathies and synucleinopathies, followed by seed-dependent propagation. There is a long prodromal phase between the formation of protein aggregates and the appearance of the first clinical symptoms, which manifest only after extensive propagation, opening novel therapeutic avenues. PMID- 27658419 TI - A novel approach to identifying patterns of human invasion-inhibitory antibodies guides the design of malaria vaccines incorporating polymorphic antigens. AB - BACKGROUND: The polymorphic nature of many malaria vaccine candidates presents major challenges to achieving highly efficacious vaccines. Presently, there is very little knowledge on the prevalence and patterns of functional immune responses to polymorphic vaccine candidates in populations to guide vaccine design. A leading polymorphic vaccine candidate against blood-stage Plasmodium falciparum is apical membrane antigen 1 (AMA1), which is essential for erythrocyte invasion. The importance of AMA1 as a target of acquired human inhibitory antibodies, their allele specificity and prevalence in populations is unknown, but crucial for vaccine design. METHODS: P. falciparum lines expressing different AMA1 alleles were genetically engineered and used to quantify functional antibodies from two malaria-exposed populations of adults and children. The acquisition of AMA1 antibodies was also detected using enzyme linked immunosorbent assay (ELISA) and competition ELISA (using different AMA1 alleles) from the same populations. RESULTS: We found that AMA1 was a major target of naturally acquired invasion-inhibitory antibodies that were highly prevalent in malaria-endemic populations and showed a high degree of allele specificity. Significantly, the prevalence of inhibitory antibodies to different alleles varied substantially within populations and between geographic locations. Inhibitory antibodies to three specific alleles were highly prevalent (FVO and W2mef in Papua New Guinea; FVO and XIE in Kenya), identifying them for potential vaccine inclusion. Measurement of antibodies by standard or competition ELISA was not strongly predictive of allele-specific inhibitory antibodies. The patterns of allele-specific functional antibody responses detected with our novel assays may indicate that acquired immunity is elicited towards serotypes that are prevalent in each geographic location. CONCLUSIONS: These findings provide new insights into the nature and acquisition of functional immunity to a polymorphic vaccine candidate and strategies to quantify functional immunity in populations to guide rational vaccine design. PMID- 27658421 TI - Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy? AB - Thalamic deep brain stimulation is a mainstay treatment for severe and drug refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. PMID- 27658422 TI - Increased Expression of System xc- in Glioblastoma Confers an Altered Metabolic State and Temozolomide Resistance. AB - : Glioblastoma multiforme is the most aggressive malignant primary brain tumor in adults. Several studies have shown that glioma cells upregulate the expression of xCT (SLC7A11), the catalytic subunit of system xc-, a transporter involved in cystine import, that modulates glutathione production and glioma growth. However, the role of system xc- in regulating the sensitivity of glioma cells to chemotherapy is currently debated. Inhibiting system xc- with sulfasalazine decreased glioma growth and survival via redox modulation, and use of the chemotherapeutic agent temozolomide together with sulfasalazine had a synergistic effect on cell killing. To better understand the functional consequences of system xc- in glioma, stable SLC7A11-knockdown and -overexpressing U251 glioma cells were generated. Modulation of SLC7A11 did not alter cellar proliferation but overexpression did increase anchorage-independent cell growth. Knockdown of SLC7A11 increased basal reactive oxygen species (ROS) and decreased glutathione generation resulting in increased cell death under oxidative and genotoxic stress. Overexpression of SLC7A11 resulted in increased resistance to oxidative stress and decreased chemosensitivity to temozolomide. In addition, SLC7A11 overexpression was associated with altered cellular metabolism including increased mitochondrial biogenesis, oxidative phosphorylation, and ATP generation. These results suggest that expression of SLC7A11 in the context of glioma contributes to tumorigenesis, tumor progression, and resistance to standard chemotherapy. IMPLICATIONS: SLC7A11, in addition to redox modulation, appears to be associated with increased cellular metabolism and is a mediator of temozolomide resistance in human glioma, thus making system xC- a potential therapeutic target in glioblastoma multiforme. Mol Cancer Res; 14(12); 1229-42. (c)2016 AACR. PMID- 27658424 TI - Klebsiella pneumoniae necrotizing fasciitis. PMID- 27658425 TI - Oxford in the springtime. PMID- 27658423 TI - MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway. AB - : Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C--terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known whether MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation, and apoptosis. Also shown is that MUC1-C--mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/beta-catenin complexes, and induces the WNT target gene MYC. These data support a previously unrecognized pathway in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/beta-catenin-mediated induction of MYC expression. IMPLICATIONS: These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. Mol Cancer Res; 14(12); 1266-76. (c)2016 AACR. PMID- 27658426 TI - Biomechanical effects of angular stable locking in intramedullary nails for the fixation of distal tibia fractures. AB - Treatment of distal tibia shaft fractures using intramedullary nailing requires stable fixation of the distal fragment to prevent malunion. Angular stable locking for intramedullary nails pledge to provide increased mechanical stability. This study tested the hypothesis that intramedullary nails with angular stable interlocking screws would have increased construct stiffness, reduced fracture gap movement and enhanced fatigue failure compared to nails with conventional locking having the same diameter. Biomechanical experiments were performed on 24 human cadaveric tibiae which obtained a distal fracture and were fixed by three different techniques: conventional locking with 8- and 10-mm diameter nails and angular stable locking with 8-mm nails. Stiffness of the implant-bone construct and movement of the fragments were tested under axial loading and torsion. The constructs were tested to failure under cyclic fatigue loading. Analysis of variance and Kaplan-Meier survival analysis were used for statistical assessment. Axial stiffness of the 10-mm nail was about 50% larger compared to both 8-mm nail constructs independent of the type of locking mode (p < 0.01). No differences were found in axial performance between angular stable and conventional locking neither under static nor under cyclic testing conditions (p > 0.5). Angular stability significantly decreased the clearance under torsional load by more than 50% compared to both conventionally locked constructs (p = 0.03). However, due to the larger nail diameter, the total interfragmentary motion was still smallest for the 10-mm nail construct (p < 0.01). Although the 10-mm nail constructs survived slightly longer, differences between groups were minor and not statistically significant (p = 0.4). Our hypothesis that angular stable interlocking of intramedullary nails would improve mechanical performance of distal tibia fracture fixation was not confirmed in a physiologically realistic loading scenario. Whether minor mechanical advantages provided by angular stability of the locking screws would improve biological tissue response cannot be concluded from this biomechanical study. PMID- 27658427 TI - Applications of 3D printing in the management of severe spinal conditions. AB - The latest and fastest-growing innovation in the medical field has been the advent of three-dimensional printing technologies, which have recently seen applications in the production of low-cost, patient-specific medical implants. While a wide range of three-dimensional printing systems has been explored in manufacturing anatomical models and devices for the medical setting, their applications are cutting-edge in the field of spinal surgery. This review aims to provide a comprehensive overview and classification of the current applications of three-dimensional printing technologies in spine care. Although three dimensional printing technology has been widely used for the construction of patient-specific anatomical models of the spine and intraoperative guide templates to provide personalized surgical planning and increase pedicle screw placement accuracy, only few studies have been focused on the manufacturing of spinal implants. Therefore, three-dimensional printed custom-designed intervertebral fusion devices, artificial vertebral bodies and disc substitutes for total disc replacement, along with tissue engineering strategies focused on scaffold constructs for bone and cartilage regeneration, represent a set of promising applications towards the trend of individualized patient care. PMID- 27658428 TI - A Study on the Validity of a Computer-Based Game to Assess Cognitive Processes, Reward Mechanisms, and Time Perception in Children Aged 4-8 Years. AB - BACKGROUND: A computer-based game, named Timo's Adventure, was developed to assess specific cognitive functions (eg, attention, planning, and working memory), time perception, and reward mechanisms in young school-aged children. The game consists of 6 mini-games embedded in a story line and includes fantasy elements to enhance motivation. OBJECTIVE: The aim of this study was to investigate the validity of Timo's Adventure in normally developing children and in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: A total of 96 normally developing children aged 4-8 years and 40 children with ADHD were assessed using the game. Clinical validity was investigated by examining the effects of age on performances within the normally developing children, as well as performance differences between the healthy controls and the ADHD group. RESULTS: Our analyses in the normally developing children showed developmental effects; that is, older children made fewer inhibition mistakes (r=-.33, P=.001), had faster (and therefore better) reaction times (r=-.49, P<.001), and were able to produce time intervals more accurately than younger children (rho=.35, P<.001). Discriminant analysis showed that Timo's Adventure was accurate in most classifications whether a child belonged to the ADHD group or the normally developing group: 78% (76/97) of the children were correctly classified as having ADHD or as being in the normally developing group. The classification results showed that 72% (41/57) children in the control group were correctly classified, and 88% (35/40) of the children in the ADHD group were correctly classified as having ADHD. Sensitivity (0.89) and specificity (0.69) of Timo's Adventure were satisfying. CONCLUSIONS: Computer-based games seem to be a valid tool to assess specific strengths and weaknesses in young children with ADHD. PMID- 27658429 TI - Biophysical tools to assess the interaction of PF4 with polyanions. AB - The antigen in heparin-induced thrombocytopenia (HIT) is expressed on platelet factor 4 (PF4) when PF4 complexes with polyanions. In recent years, biophysical tools (e. g. circular dichroism spectroscopy, atomic force microscopy, isothermal titration calorimetry, x-ray crystallography, electron microscopy) have gained an important role to complement immunological and functional assays for better understanding the interaction of heparin with PF4. This allowed identification of those features that make PF4 immunogenic (e. g. a certain conformational change induced by the polyanion, a threshold energy of the complexes, the existence of multimeric complexes, a certain number of bonds formed by PF4 with the polyanion) and to characterize the morphology and thermal stability of complexes formed by the protein with polyanions. These findings and methods can now be applied to test new drugs for their potential to induce the HIT-like adverse drug effect by preclinical in vitro testing. The methods and techniques applied to characterize the antigen in HIT may also be helpful to better understand the mechanisms underlying other antibody-mediated disorders in thrombosis and hemostasis (e. g. acquired hemophilia, thrombotic thrombocytopenic purpura). Furthermore, understanding the mechanisms making the endogenous protein PF4 immunogenic may help to understand the mechanisms underlying other autoimmune disorders. PMID- 27658430 TI - [Fingolimod in Spain: usual clinical practice]. PMID- 27658431 TI - [Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Galicia]. AB - INTRODUCTION: The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet, due to their limitations, it is important to know how it behaves under everyday clinical practice conditions. Hence, the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months' usage in clinical practice in Galicia. PATIENTS AND METHODS: We conducted a retrospective, multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod, 0.5 mg/day. Effectiveness was assessed annualised relapse rate (ARR), changes in the score on the Expanded Disability Status Scale (EDSS), percentage of patients free from relapses, free from progression of disability and free from activity in resonance- for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. RESULTS: After 12 months' use, fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and, consequently, 81% of patients were free from relapses. The score was reduced by 9%. In all, 91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects, but only 2% of them withdrew for this reason. CONCLUSIONS: In clinical practice, most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials. PMID- 27658432 TI - [Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Asturias and Cantabria]. AB - AIM: To evaluate the effectiveness and safety of fingolimod in routine clinical practice in the region of Asturias and Cantabria (Spain). PATIENTS AND METHODS: We conducted a retrospective multicentre study of patients with relapsing remitting multiple sclerosis treated with fingolimod, in accordance with the product data sheet. Effectiveness was evaluated in patients with at least one year's treatment. The following were calculated: annualised relapse rate (ARR), the percentage of patients free from relapses and free from gadolinium-enhancing lesions, and those who improved/maintained their score on the Expanded Disability Status Scale (EDSS). Both total population and according to previous treatment: immunomodulator (interferon beta-1 or glatiramer acetate) or natalizumab, were analysed. RESULTS: A total of 138 patients started treatment with fingolimod; 60% previously received an immunomodulator; 28% were given natalizumab; and 9% had no treatment. Ninety-nine patients were treated with fingolimod for at least one year. After one year of treatment, fingolimod decreased the ARR by 67% (1.26 to 0.42; p < 0.0001), increased the percentage of patients free from relapses from 24% to 69% (p < 0.0001) and the percentage of patients free from gadolinium enhancing lesions from 70% to 85% (p < 0.0106). Altogether, 77% of the patients improved/maintained their score on the EDSS. Similar results were observed in patients previously treated with an immunomodulator. The effectiveness of the patients previously treated with natalizumab remained the same following treatment with fingolimod. CONCLUSIONS: Routine clinical practice in the regions of Asturias and Cantabria shows that fingolimod yields similar results to those observed in clinical trials, on comparing the clinicoradiological variables used in them. PMID- 27658433 TI - [Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in the province of Alicante]. AB - INTRODUCTION: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice. AIMS: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante. PATIENTS AND METHODS: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod. Demographic, clinical and pharmacological data were collected. We report on the effectiveness of the drug -annualised relapse rate (ARR) and percentage of patients free from attacks- at one and at two years after treatment in relation to the previous year, and data concerning side effects are also provided. RESULTS: The sample consisted of 89 patients. Previous treatment was with immunomodulators (interferon beta or glatiramer acetate) in 54 patients and natalizumab in 32. Fifty patients changed due to failure with the immunomodulator and 31 owing to positive serology for JC virus (JCV+). Overall ARR decreased by 67.3% the first year (p < 0.0001) and by 84.1% the second (p = 0.0078). It diminished in patients with immunomodulator failure (85.6% the first year, p < 0.0001; 88.9% the second year, p = 0.0039) and increased in a non-significant manner in JCV+ patients in the first year. The percentage of patients free from relapses in the overall population increased from 32.6% to 68.1% in the first year (p < 0.0019) and to 82.6% in the second (p = 0.0215). This increase was not observed in JCV+ patients. Side effects were reported by 13 patients, which led to the drug being withdrawn in two of them. CONCLUSION: In clinical practice in the province of Alicante, levels of effectiveness and safety of fingolimod proved to be slightly higher than those found in clinical trials. PMID- 27658434 TI - [Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Navarra, Gipuzkoa and La Rioja]. AB - AIM: To evaluate the effectiveness and safety of fingolimod in clinical practice in Navarra, Gipuzkoa and La Rioja regions. PATIENTS AND METHODS: We conducted a retrospective multi-centre study with recurrent multiple sclerosis patients treated with fingolimod, following the product data sheet. The following data were evaluated: annualised relapse rate (ARR), percentage of patients free from relapses, disability using the Expanded Disability Status Scale (EDSS) and the percentage of patients without gadolinium-enhancing lesions. RESULTS: A total of 113 patients were treated with fingolimod: 6% were naive, and 58% and 35% were patients previously treated with an immunomodulator and natalizumab, respectively. Fingolimod lowered the ARR after the first (67%; 1 to 0.3; p < 0.0001) and second (89%; 1 to 0.1; p < 0.0001) years of treatment, and thus the number of patients free from relapses during the treatment increased. The baseline EDSS was 3 and after treatment with fingolimod was 2.5 in both years. The percentage of patients without gadolinium-enhancing lesions after the first year of treatment was 77%. Similar results were observed in naive patients and in those previously treated with an immunomodulator. In patients previously treated with natalizumab no changes were observed following the treatment. CONCLUSIONS: The use of fingolimod in clinical practice showed an effectiveness similar to that observed in clinical trials. There were no changes in the ARR after changing from natalizumab, and only one patient presented a 'relapse' after withdrawal of natalizumab. Fingolimod acts like a safe drug, with scarce side effects and a low percentage of drop-outs. PMID- 27658435 TI - Due to interleukin-6 type cytokine redundancy only glycoprotein 130 receptor blockade efficiently inhibits myeloma growth. AB - Interleukin-6 has an important role in the pathophysiology of multiple myeloma where it supports the growth and survival of the malignant plasma cells in the bone marrow. It belongs to a family of cytokines which use the glycoprotein 130 chain for signal transduction, such as oncostatin M or leukemia inhibitory factor. Targeting interleukin-6 in plasma cell diseases is currently evaluated in clinical trials with monoclonal antibodies. Here, efforts were made to elucidate the contribution of interleukin-6 and glycoprotein 130 signaling in malignant plasma cell growth in vivo In the xenograft severe combined immune deficiency model employing our interleukin-6-dependent plasma cell line INA-6, the lack of human interleukin-6 induced autocrine interleukin-6 production and a proliferative response to other cytokines of the glycoprotein 130 family. Herein, mice were treated with monoclonal antibodies against human interleukin-6 (elsilimomab/B-E8), the interleukin-6 receptor (B-R6), and with an antibody blocking glycoprotein 130 (B-R3). While treatment of mice with interleukin-6 and interleukin-6 receptor antibodies resulted in a modest delay in tumor growth, the development of plasmacytomas was completely prevented with the anti-glycoprotein 130 antibody. Importantly, complete inhibition was also achieved using F(ab')2 fragments of monoclonal antibody B-R3. Tumors harbor activated signal transducer and activator of transcription 3, and in vitro, the antibody inhibited leukemia inhibitory factor stimulated signal transducer and activator of transcription 3 phosphorylation and cell growth, while being less effective against interleukin 6. In conclusion, the growth of INA-6 plasmacytomas in vivo under interleukin-6 withdrawal remains strictly dependent on glycoprotein 130, and other glycoprotein 130 cytokines may substitute for interleukin-6. Antibodies against glycoprotein 130 are able to overcome this redundancy and should be explored for a possible therapeutic window. PMID- 27658436 TI - APOL1, alpha-thalassemia, and BCL11A variants as a genetic risk profile for progression of chronic kidney disease in sickle cell anemia. PMID- 27658437 TI - A plasma microRNA signature as a biomarker for acquired aplastic anemia. AB - Aplastic anemia is an acquired bone marrow failure characterized by marrow hypoplasia, a paucity of hematopoietic stem and progenitor cells, and pancytopenia of the peripheral blood, due to immune attack on the bone marrow. In aplastic anemia, a major challenge is to develop immune biomarkers to monitor the disease. We measured circulating microRNAs in plasma samples of aplastic anemia patients in order to identify disease-specific microRNAs. A total of 179 microRNAs were analyzed in 35 plasma samples from 13 aplastic anemia patients, 11 myelodysplastic syndrome patients, and 11 healthy controls using the Serum/Plasma Focus microRNA Polymerase Chain Reaction Panel. Subsequently, 19 microRNAs from the discovery set were investigated in the 108 plasma samples from 41 aplastic anemia patients, 24 myelodysplastic syndrome patients, and 43 healthy controls for validation, confirming that 3 microRNAs could be validated as dysregulated (>1.5-fold change) in aplastic anemia, compared to healthy controls. MiR-150-5p (induction of T-cell differentiation) and miR-146b-5p (involvement in the feedback regulation of innate immune response) were elevated in aplastic anemia plasma, whereas miR-1 was decreased in aplastic anemia. By receiver operating characteristic curve analysis, we developed a logistic model with these 3 microRNAs that enabled us to predict the probability of a diagnosis of aplastic anemia with an area under the curve of 0.86. Dysregulated expression levels of the microRNAs became normal after immunosuppressive therapy at 6 months. Specifically, miR-150-5p expression was significantly reduced after successful immunosuppressive therapy, but did not change in non-responders. We propose 3 novel plasma biomarkers in aplastic anemia, in which miR-150-5p, miR-146b-5p, and miR-1 can serve for diagnosis and miR-150-5p for disease monitoring. Clinicaltrials.gov identifiers:00260689, 00217594, 00961064. PMID- 27658438 TI - Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes. AB - Flow cytometric analysis is a recommended tool in the diagnosis of myelodysplastic syndromes. Current flow cytometric approaches evaluate the (im)mature myelo-/monocytic lineage with a median sensitivity and specificity of ~71% and ~93%, respectively. We hypothesized that the addition of erythroid lineage analysis could increase the sensitivity of flow cytometry. Hereto, we validated the analysis of erythroid lineage parameters recommended by the International/European LeukemiaNet Working Group for Flow Cytometry in Myelodysplastic Syndromes, and incorporated this evaluation in currently applied flow cytometric models. One hundred and sixty-seven bone marrow aspirates were analyzed; 106 patients with myelodysplastic syndromes, and 61 cytopenic controls. There was a strong correlation between presence of erythroid aberrancies assessed by flow cytometry and the diagnosis of myelodysplastic syndromes when validating the previously described erythroid evaluation. Furthermore, addition of erythroid aberrancies to two different flow cytometric models led to an increased sensitivity in detecting myelodysplastic syndromes: from 74% to 86% for the addition to the diagnostic score designed by Ogata and colleagues, and from 69% to 80% for the addition to the integrated flow cytometric score for myelodysplastic syndromes, designed by our group. In both models the specificity was unaffected. The high sensitivity and specificity of flow cytometry in the detection of myelodysplastic syndromes illustrates the important value of flow cytometry in a standardized diagnostic approach. The trial is registered at www.trialregister.nl as NTR1825; EudraCT n.: 2008-002195-10. PMID- 27658440 TI - A randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy. AB - INTRODUCTION: Vaginal tenofovir (TFV) 1% gel may reduce incident HIV-1 and herpes simplex virus 2 infection. Pregnancy may increase risk of HIV acquisition, and incident HIV in pregnancy potentiates perinatal HIV transmission. Our objective was to investigate the safety and pharmacokinetics of seven days of TFV 1% vaginal gel in term and near-term pregnancy. METHODS: Ninety-eight healthy pregnant women, stratified to a term cohort followed by a near-term cohort, were enrolled into a 2:1 randomized, double-blinded, placebo-controlled trial. Women received TFV or placebo gel for seven consecutive days with pharmacokinetic sampling on days 0 and 6. Maternal and cord blood were collected at delivery. Primary end points included laboratory and genital adverse events, adverse pregnancy and neonatal outcomes, and maternal TFV levels. RESULTS: Most adverse events were grade 1 and none of the grade 3 or 4 adverse events were related to study product. There was no significant difference in safety end points between the two pregnancy cohorts (p=0.18); therefore, their data were combined. Primary safety end point rates were similar for mothers randomized to the TFV gel vs placebo arm (72.7 and 68.8%, p=0.81). The same was true for newborns in the TFV gel vs placebo arms (4.5% vs 6.3%, p=0.66). All women randomized to TFV had quantifiable serum levels within eight hours of dosing, with low overall median (interquartile range) day 0 and day 6 peak values (3.8 (2.0 to 7.0) and 5.8 (2.6 to 9.4) ng/mL, respectively). CONCLUSIONS: Daily TFV 1% vaginal gel use in term and near-term pregnancy appears to be safe and produces low serum drug levels. PMID- 27658439 TI - Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia. AB - Malaria, a major global health challenge worldwide, is accompanied by a severe anemia secondary to hemolysis and increased erythrophagocytosis. Iron is an essential functional component of erythrocyte hemoglobin and its availability is controlled by the liver-derived hormone hepcidin. We examined the regulation of hepcidin during malarial infection in mice using the rodent parasite Plasmodium berghei K173. Mice infected with Plasmodium berghei K173 develop a severe anemia and die after 18 to 22 days without cerebral malaria. During the early phase of blood-stage infection (days 1 to 5), a strong inflammatory signature was associated with an increased production of hepcidin. Between days 7 and 18, while infection progressed, red blood cell count, hemoglobin and hematocrit dramatically decreased. In the late phase of malarial infection, hepcidin production was reduced concomitantly to an increase in the messenger RNA expression of the hepcidin suppressor erythroferrone in the bone marrow and the spleen. Compared with wild-type mice, Erfe-/- mice failed to adequately suppress hepcidin expression after infection with Plasmodium berghei K173. Importantly, the sustained production of hepcidin allowed by erythroferrone ablation was associated with decreased parasitemia, providing further evidence that transient iron restriction could be beneficial in the treatment of malaria. PMID- 27658441 TI - Flyglow: Single-fly observations of simultaneous molecular and behavioural circadian oscillations in controls and an Alzheimer's model. AB - Circadian rhythms are essential for health and are frequently disturbed in disease. A full understanding of the causal relationships between behavioural and molecular circadian rhythms requires simultaneous longitudinal observations over time in individual organisms. Current experimental paradigms require the measurement of each rhythm separately across distinct populations of experimental organisms, rendering the comparability of the resulting datasets uncertain. We therefore developed FLYGLOW, an assay using clock gene controlled luciferase expression detected by exquisitely sensitive EM-CCD imaging, to enable simultaneous quantification of parameters including locomotor, sleep consolidation and molecular rhythms in single flies over days/weeks. FLYGLOW combines all the strengths of existing techniques, and also allows powerful multiparametric paired statistics. We found the age-related transition from rhythmicity to arrhythmicity for each parameter occurs unpredictably, with some flies showing loss of one or more rhythms during middle-age. Using single-fly correlation analysis of rhythm robustness and period we demonstrated the independence of the peripheral clock from circadian behaviours in wild type flies as well as in an Alzheimer's model. FLYGLOW is a useful tool for investigating the deterioration of behavioural and molecular rhythms in ageing and neurodegeneration. This approach may be applied more broadly within behavioural neurogenetics research. PMID- 27658442 TI - The MADS-Box transcription factor Bcmads1 is required for growth, sclerotia production and pathogenicity of Botrytis cinerea. AB - MADS-box transcription factors are highly conserved in eukaryotic species and involved in a variety of biological processes. Little is known, however, regarding the function of MADS-box genes in Botrytis cinerea, a fungal pathogen with a wide host range. Here, the functional role of the B. cinerea MADS-box gene, Bcmads1, was characterized in relation to the development, pathogenicity and production of sclerotia. The latter are formed upon incubation in darkness and serve as survival structures during winter and as the female parent in sexual reproduction. Bcmads1 is indispensable for sclerotia production. RT-qPCR analysis suggested that Bcmads1 modulated sclerotia formation by regulating the expression of light-responsive genes. Bcmads1 is required for the full virulence potential of B. cinerea on apple fruit. A comparative proteomic analysis identified 63 proteins, representing 55 individual genes that are potential targets of Bcmads1. Among them, Bcsec14 and Bcsec31 are associated with vesicle transport. Deletion of Bcsec14 and Bcsec31 resulted in a reduction in the virulence and protein secretion of B. cinerea. These results suggest that Bcmads1 may influence sclerotia formation by modulating light responsive gene expression and regulate pathogenicity by its effect on the protein secretion process. PMID- 27658444 TI - The conservative behavior of dissolved organic carbon in surface waters of the southern Chukchi Sea, Arctic Ocean, during early summer. AB - The spatial distribution of dissolved organic carbon (DOC) concentrations and the optical properties of dissolved organic matter (DOM) determined by ultraviolet visible absorbance and fluorescence spectroscopy were measured in surface waters of the southern Chukchi Sea, western Arctic Ocean, during the early summer of 2013. Neither the DOC concentration nor the optical parameters of the DOM correlated with salinity. Principal component analysis using the DOM optical parameters clearly separated the DOM sources. A significant linear relationship was evident between the DOC and the principal component score for specific water masses, indicating that a high DOC level was related to a terrigenous source, whereas a low DOC level was related to a marine source. Relationships between the DOC and the principal component scores of the surface waters of the southern Chukchi Sea implied that the major factor controlling the distribution of DOC concentrations was the mixing of plural water masses rather than local production and degradation. PMID- 27658443 TI - Multipath Effects in Millimetre-Wave Wireless Communication using Orbital Angular Momentum Multiplexing. AB - Electromagnetic waves carrying orbital angular momentum (OAM) have been used for mode division multiplexing in free-space communication systems to increase both the capacity and the spectral efficiency. In the case of conventional wireless communication links using non-OAM beams, multipath effects caused by beam spreading and reflection from the surrounding objects affect the system performance. This paper presents the results of analysis, simulations, and measurements of multipath effects in a millimetre-wave communication link using OAM multiplexing at 28 GHz. Multipath-induced intra- and inter-channel crosstalk, which are caused by specular reflection from a plane parallel to the propagation path, are analysed and measured. Both the simulation and the experimental results show that an OAM channel with a high OAM number l tends to suffer from both strong intra-channel crosstalk and strong inter-channel crosstalk with other OAM channels. Results of the analysis show that this observation can be explained on the basis of both the properties of OAM beam divergence and the filtering effect at the receiver, which is associated with the spiral wavefront of OAM beams. PMID- 27658445 TI - Flavonoids are determinants of freezing tolerance and cold acclimation in Arabidopsis thaliana. AB - In plants from temperate climates such as Arabidopsis thaliana low, non-freezing temperatures lead to increased freezing tolerance in a process termed cold acclimation. This process is accompanied by massive changes in gene expression and in the content of primary metabolites and lipids. In addition, most flavonols and anthocyanins accumulate upon cold exposure, along with most transcripts encoding transcription factors and enzymes of the flavonoid biosynthetic pathway. However, no evidence for a functional role of flavonoids in plant freezing tolerance has been shown. Here, we present a comprehensive analysis using qRT-PCR for transcript, LC-MS for flavonoid and GC-MS for primary metabolite measurements, and an electrolyte leakage assay to determine freezing tolerance of 20 mutant lines in two Arabidopsis accessions that are affected in different steps of the flavonoid biosynthetic pathway. This analysis provides evidence for a functional role of flavonoids in plant cold acclimation. The accumulation of flavonoids in the activation tagging mutant line pap1-D improved, while reduced flavonoid content in different knock-out mutants impaired leaf freezing tolerance. Analysis of the different knock-out mutants suggests redundancy of flavonoid structures, as the lack of flavonols or anthocyanins could be compensated by other compound classes. PMID- 27658446 TI - Full-Color Biomimetic Photonic Materials with Iridescent and Non-Iridescent Structural Colors. AB - The beautiful structural colors in bird feathers are some of the brightest colors in nature, and some of these colors are created by arrays of melanin granules that act as both structural colors and scattering absorbers. Inspired by the color of bird feathers, high-visibility structural colors have been created by altering four variables: size, blackness, refractive index, and arrangement of the nano-elements. To control these four variables, we developed a facile method for the preparation of biomimetic core-shell particles with melanin-like polydopamine (PDA) shell layers. The size of the core-shell particles was controlled by adjusting the core polystyrene (PSt) particles' diameter and the PDA shell thicknesses. The blackness and refractive index of the colloidal particles could be adjusted by controlling the thickness of the PDA shell. The arrangement of the particles was controlled by adjusting the surface roughness of the core-shell particles. This method enabled the production of both iridescent and non-iridescent structural colors from only one component. This simple and novel process of using core-shell particles containing PDA shell layers can be used in basic research on structural colors in nature and their practical applications. PMID- 27658447 TI - Shiny condensates. PMID- 27658448 TI - Physics and applications of exciton-polariton lasers. PMID- 27658449 TI - Organic light-emitting diodes: High-throughput virtual screening. PMID- 27658450 TI - Active colloids: Controlled collective motions. PMID- 27658451 TI - Karl A. Gschneidner Jr (1930-2016). PMID- 27658452 TI - Material witness: Close to the edge. PMID- 27658453 TI - Transcriptome responses of an ungrafted Phytophthora root rot tolerant avocado (Persea americana) rootstock to flooding and Phytophthora cinnamomi. AB - BACKGROUND: Avocado (Persea americana Mill.) is a commercially important fruit crop worldwide. A major limitation to production is the oomycete Phytophthora cinnamomi, which causes root rot leading to branch-dieback and tree death. The decline of orchards infected with P. cinnamomi occurs much faster when exposed to flooding, even if flooding is only transient. Flooding is a multifactorial stress compromised of several individual stresses, making breeding and selection for tolerant varieties challenging. With more plantations occurring in marginal areas, with imperfect irrigation and drainage, understanding the response of avocado to these stresses will be important for the industry. RESULTS: Maintenance of energy production was found to be central in the response to flooding, as seen by up-regulation of transcripts related to glycolysis and induction of transcripts related to ethanolic fermentation. Energy-intensive processes were generally down-regulated, as evidenced by repression of transcripts related to processes such as secondary cell-wall biosynthesis as well as defence-related transcripts. Aquaporins were found to be down-regulated in avocado roots exposed to flooding, indicating reduced water-uptake under these conditions. CONCLUSIONS: The transcriptomic response of avocado to flooding and P. cinnamomi was investigated utilizing microarray analysis. Differences in the transcriptome caused by the presence of the pathogen were minor compared to transcriptomic perturbations caused by flooding. The transcriptomic response of avocado to flooding reveals a response to flooding that is conserved in several species. This data could provide key information that could be used to improve selection of stress tolerant rootstocks in the avocado industry. PMID- 27658454 TI - Resilience of a FIT screening programme against screening fatigue: a modelling study. AB - BACKGROUND: Repeated participation is important in faecal immunochemical testing (FIT) screening for colorectal cancer (CRC). However, a large number of screening invitations over time may lead to screening fatigue and consequently, decreased participation rates. We evaluated the impact of screening fatigue on overall screening programme effectiveness. METHODS: Using the ASCCA model, we simulated the Dutch CRC screening programme consisting of biennial FIT screening in individuals aged 55-75. We studied the resilience of the programme against heterogeneity in screening attendance and decrease in participation rate due to screening fatigue. Outcomes were reductions in CRC incidence and mortality compared to no screening. RESULTS: Assuming a homogenous 63 % participation, i.e., each round each individual was equally likely to attend screening, 30 years of screening reduced CRC incidence and mortality by 39 and 53 %, respectively, compared to no screening. When assuming clustered participation, i.e., three subgroups of individuals with a high (95 %), moderate (65 %) and low (5 %) participation rate, screening was less effective; reductions were 33 % for CRC incidence and 43 % for CRC mortality. Screening fatigue considerably reduced screening effectiveness; if individuals refrained from screening after three negative screens, model-predicted incidence reductions decreased to 25 and 18 % under homogenous and clustered participation, respectively. Figures were 34 and 25 % for mortality reduction. CONCLUSIONS: Screening will substantially decrease CRC incidence and mortality. However, screening effectiveness can be seriously compromised if screening fatigue occurs. This warrants careful monitoring of individual screening behaviour and consideration of targeted invitation systems in individuals who have (repeatedly) missed screening rounds. PMID- 27658456 TI - Bacterial vaginosis and adverse outcomes among full-term infants: a cohort study. AB - BACKGROUND: Bacterial vaginosis (BV) during pregnancy is a well-established risk factor for preterm birth and other preterm pregnancy complications. Little is known about adverse neonatal outcomes associated with BV exposure in full-term births, nor its influence on adverse outcomes independent of its effect on gestational age. The purpose of this study was to examine the relationship between BV during pregnancy and adverse neonatal outcomes among full-term and preterm infants. METHODS: We conducted a retrospective cohort study of Washington State mother/infant pairs from 2003-2013, stratified by full-term (primary outcomes) and preterm births (secondary outcomes). BV-exposed and unexposed women were frequency-matched based on year of delivery. BV exposure and adverse outcomes [assisted ventilation/respiratory distress, neonatal intensive care unit (NICU) admission, neonatal sepsis, fetal mortality, and infant mortality] were identified using birth certificates, ICD-9 codes from linked hospital records, and death certificates. Associations between BV exposure and outcomes were assessed using multivariable Poisson regression, adjusted for maternal demographics, gestational age, and other pregnancy complications, including infections. RESULTS: A total of 12,340 mother/infant pairs were included: 2,468 BV-exposed (2198 term, 267 preterm) and 9,872 BV unexposed (9156 term, 708 preterm). Among full-term infants, BV-exposed mothers were younger, more likely to be Black or Hispanic, more likely to have had a sexually transmitted infection, and less likely to have a college degree than unexposed mothers. Term BV exposed infants were more likely to have meconium at delivery. Following adjustment, BV was associated with an increased risk of assisted ventilation/respiratory distress at birth (aRR = 1.28, 95 % CI 1.02-1.61), NICU admission (aRR = 1.42, 95 % CI 1.11-1.82), and neonatal sepsis (aRR = 1.60, 95 % CI 1.13-2.27) among full-term infants. These associations were independent of the presence of chorioamnionitis or meconium. Among preterm infants, BV-exposure was associated with an increased risk for NICU admissions only (aRR = 1.24, 95 % CI 1.04-1.46). CONCLUSIONS: BV exposure during pregnancy is associated with adverse neonatal outcomes even among infants born full-term. These findings amongst full term infants are novel, and highlight neonatal implications of BV in pregnancy independent of BV's effect on preterm birth. PMID- 27658455 TI - Enhancement of the BG-sentinel trap with varying number of mice for field sampling of male and female Aedes albopictus mosquitoes. AB - BACKGROUND: Trapping male mosquitoes in the field is essential for the development of area-wide vector control programs with a sterile insect technique (SIT) component. To determine the optimal temporal and spatial release strategy, an estimation of the wild population density and its temporal dynamics is essential. Among the traps available for such data collection, the BG-Sentinel trap developed by the Biogents company uses a combination of visual cues, convection currents and olfactory signals. Although in numerous cases, this trap has shown high efficiency in sampling Aedes albopictus, in some cases low capture rates of Ae. albopictus males were recorded for the BG-sentinel mosquito trap baited with synthetic attractants. METHODS: The effects of modifying the BG sentinel trap (by adding one mouse, two or three live mice to the trap) on the efficiency of trapping Ae. albopictus males and females was tested. The experiment was carried out in three distinct areas on La Reunion that have been selected for pilot field testing of the release of sterile male Ae. albopictus mosquitoes. The effect of four types of attractant (including the generic BG Lure, one mouse or two to three mice) in baited BGS traps was tested with a Latin square design in order to control for the variability of different sampling positions and dates. RESULTS: At the three studied sites, the number of Ae. albopictus adults caught and the proportion of males per trap consistently increased with the number of mice present in the trap. CONCLUSION: The results from this study suggest that some new attractants derived from, or similar to, mouse odors could be developed and tested in combination with other existing attractive components, such as CO2 and heat, in order to provide a reliable estimation method for Ae. albopictus adult male abundance in the wild. PMID- 27658458 TI - Chronic fibrosing pulmonary aspergillosis: a cause of 'destroyed lung' syndrome. AB - BACKGROUND: Chronic pulmonary aspergillosis (CPA) has substantial impact on quality of life. A subset of patients develops significant pulmonary fibrosis, identified either on biopsy or radiologically. The term chronic fibrosing pulmonary aspergillosis (CFPA) has been suggested. METHODS: We describe 11 patients with CFPA referred to our centre. RESULTS: Mean age was 58.5 years and five were male. In nine, fibrosis was already evident on presentation, while in two it developed 3 and 6 years later. The predominant radiological feature was extensive or complete involvement of the entire lung, with minimal contralateral involvement. All patients received prolonged antifungal treatment. Two patients had surgical treatment; both developed post-operative complications. The contralateral lung remained free of significant disease in all but three patients. CONCLUSIONS: CFPA is a rare complication of CPA that is usually evident on presentation, but may develop after years in patients not on antifungals. Fibrosis resembles the 'destroyed lung' syndrome described after treated tuberculosis. PMID- 27658459 TI - Resistin as an inflammatory marker in patients with schizophrenia treated with clozapine. AB - BACKGROUND: Schizophrenia is associated with excess cardiovascular comorbidity and mortality related to lifestyle factors, such as lack of physical activity, poor diet, and smoking. The prevalence of metabolic syndrome is increased among patients with schizophrenia, with the highest rates among patients on clozapine treatment. Smoking, obesity, physical inactivity, airway inflammation and obstruction, and adipose tissue and inflammatory marker activation are related in systemic inflammation. Low-grade inflammation is also associated with schizophrenia. Adipokine resistin is a biomarker involving several acute and chronic inflammatory states. However, the inflammatory role of resistin is so far inconclusive and studies in schizophrenia are scanty. AIMS: The aim of the present study was to explore the role of serum resistin as an inflammatory marker in patients with schizophrenia on clozapine treatment. METHODS: Associations between serum levels of resistin and some other selected cytokines/adipokines (adiponectin, leptin, adipsin, IL-6, IL-1Ra, TNF-alpha, hs-CRP) and metabolic markers in 190 patients with schizophrenia on clozapine treatment were studied using a cross-sectional study design. RESULTS: Among male patients especially, smokers had higher levels of resistin than non-smokers, and among smokers resistin levels were associated with IL-1Ra and hs-CRP levels. In the whole patient group levels of resistin associated with levels of IL-1Ra, and among male patients with low HDL-cholesterol. CONCLUSIONS: Resistin is a biomarker of systemic inflammation associated with smoking among patients with schizophrenia on clozapine treatment. Resistin might have a role as a marker of cardiovascular comorbidity. PMID- 27658457 TI - The association between maternal and partner experienced racial discrimination and prenatal perceived stress, prenatal and postnatal depression: findings from the growing up in New Zealand cohort study. AB - BACKGROUND: A growing number of studies document the association between maternal experiences of racial discrimination and adverse children's outcomes, but our understanding of how experiences of racial discrimination are associated with pre and post-natal maternal mental health, is limited. In addition, existent literature rarely takes into consideration racial discrimination experienced by the partner. METHODS: We analysed data from the Growing Up in New Zealand study to examine the burden of lifetime and past year experiences of racial discrimination on prenatal and postnatal mental health among Maori, Pacific, and Asian women in New Zealand (NZ), and to study the individual and joint contribution of mother's and partner's experiences of lifetime and past year racial discrimination to women's prenatal and postnatal mental health. RESULTS: Our findings show strong associations between lifetime and past year experiences of ethnically-motivated interpersonal attacks and unfair treatment on mother's mental health. Maori, Pacific, and Asian women who had experienced unfair treatment by a health professional in their lifetime were 66 % more likely to suffer from postnatal depression, compared to women who did not report these experiences. We found a cumulative effect of lifetime experiences of ethnically motivated personal attacks on poor maternal mental health if both the mother and the partner had experienced a racist attack. CONCLUSIONS: Experiences of racial discrimination have severe direct consequences for the mother's mental health. Given the importance of mother's mental health for the basic human needs of a healthy child, racism and racial discrimination should be addressed. PMID- 27658460 TI - Whole-Virus Screening to Develop Synbodies for the Influenza Virus. AB - There is an ongoing need for affinity agents for emerging viruses and new strains of current human viruses. We therefore developed a robust and modular system for engineering high-affinity synbody ligands for the influenza A/Puerto Rico/8/1934 H1N1 virus as a model system. Whole-virus screening against a peptide microarray was used to identify binding peptides. Candidate peptides were linked to bis maleimide peptide scaffolds to produce a library of candidate influenza-binding synbodies. From this library, a candidate synbody, ASU1060, was selected and affinity-improved via positional substitution using d-amino acids to produce a new synbody, ASU1061, that bound H1N1 in an ELISA assay with a KD of <1 nM, comparable to that of a monoclonal antibody for neuraminidase (NA). We prepared a modified version of ASU1061 that contained an additional C-terminal peptide to simulate conjugation of the synbody to a carrier protein, called ASU1063, and found that H1N1 binding was unchanged. Subsequent work identified the synbody target as nucleoprotein (NP), a highly conserved protein in influenza, with a KD of <1 nM for ASU1063. This suggests that virus-binding synbodies can be conjugated to carrier proteins or other moieties that could improve the therapeutic profile of the resulting synbody. This method is a rapid process that offers a means of developing new affinity ligands to influenza and other viruses. PMID- 27658461 TI - Primary pulmonary lymphoma: four different and unusual radiologic and clinical manifestations. PMID- 27658462 TI - Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells. AB - BACKGROUND: The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. METHODS: The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. RESULTS: The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C), alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. CONCLUSIONS: Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents. PMID- 27658464 TI - Psychometric properties of the newly developed Physician Teaching Self-Efficacy Questionnaire (PTSQ). AB - BACKGROUND: High teaching quality and students' corresponding learning progress are the most important indicators of teachers' work performance. Theory and numerous empirical studies indicate that self-efficacy, a person's belief in her or his ability to accomplish a task, is an important predictor of work performance. Accordingly, it can be assumed that teaching self-efficacy also influences teaching performance and students' learning progress with regard to physicians who teach in undergraduate medical education. Therefore, the aim of this study was to develop and validate an instrument measuring clinical teaching self-efficacy in physicians. METHODS: We developed 16 items reflecting physicians' beliefs to provide high quality clinical teaching when facing regularly occurring critical teaching situations. These constitute the Physician Teaching Self-Efficacy Questionnaire (PTSQ). For its validation, we used data from a sample of 247 physicians from internal medicine and surgery at six German medical faculties. Regarding factorial validity, we performed exploratory structural equation modelling (ESEM) as well as confirmatory factor analysis (CFA). Regarding criterion validity, correlations with the scales of the Physician Teaching Motivation Questionnaire (PTMQ), teaching experience and perceived teaching involvement were calculated. Additionally, we conducted the same analyses with a short 6-item version. RESULTS: ESEM delivered evidence for a three-factor structure with a superordinate general factor, which was confirmed by local and global fit indicators in CFA (RMSEA = .055, TLI = .939, SRMR = .048, CFI = .948). We identified the following three subfactors: teaching self-efficacy with respect to self-regulation, dyadic regulation involving students, and triadic regulation involving students and patients. Internal consistencies indicated acceptable to excellent reliability for all scales (Cronbach's alpha = .77-.90). Theory-consistent correlations with the PTMQ scales, teaching experience, and teaching involvement confirmed criterion validity. Besides excellent global fit, the short version of the PTSQ also fulfilled all other validity criteria. CONCLUSIONS: The PTSQ is a valid instrument to assess physicians' clinical teaching self-efficacy. It could be used in faculty development programmes and for educational research. The short version could be used in situations that are time-critical for physicians in order to ensure high response rates. PMID- 27658465 TI - Arterial dissection in childhood Takayasu Arteritis: not as rare as thought. AB - BACKGROUND: Arterial vessel wall dissection is a rare, life-threatening and rarely described complication in childhood Takayasu Arteritis (cTA). Prevalence and risk factors for arterial dissection in cTA are unknown. We sought to study the prevalence and analyse risk factors for arterial dissection in cTA. FINDINGS: A single center retrospective review of all children with cTA was performed. Patients with arterial dissection at cTA diagnosis were reported in detail and compared to the remaining single center retrospective cohort of children without dissection. Disease activity was assessed by the Pediatric Vasculitis Disease Activity Score (PVAS). A total of 27 cTA patients (74 % girls) were included. Three children (11 %) presented with dissection at diagnosis of cTA. They had higher PVAS (median 21 versus 10, p = 0.26), increased neutrophils (p < 0.0001) and lower albumin levels (p = 0.05). Arterial hypertension was common in both groups: in 67 % of children with dissection and 54 % of those without. CONCLUSIONS: Arterial dissection was more frequent in our cTA cohort than previously reported. Careful vascular imaging assessment is crucial to document this complication. High disease activity and markers of inflammation especially in combination with arterial hypertension, may be associated with the risk for vessel wall dissection in children with cTA. PMID- 27658467 TI - Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKKβ/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus. AB - OBJECTIVES: The present study was designed to investigate the effects of calcitriol (the active hormonal metabolite of vitamin D) on hepatic metabolic abnormalities in type 2 diabetes. METHODS: Type 2 diabetic db/db mice were used to investigate the effects of calcitriol on hepatic and systemic metabolic disorders. HepG2 cells cultured in insulin-resistant conditions were used to examine the potential mechanisms for calcitriol-induced changes in hepatic lipid and glucose metabolism. RESULTS: 8-week calcitriol treatment ameliorated abnormal hepatic lipid and glucose production in db/db mice. In HepG2 cells under insulin resistant condition, calcitriol increased cytosolic calcium concentration and induced 5'-AMP-activated protein kinase/acetyl-CoAcarboxylase (AMPK/ACC) phosphorylation via the Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) pathway, contributing to the reductions in hepatic triglyceride accumulation and glucose output. Calcitriol also induced AMPK/ACC phosphorylation in liver of db/db mice. CONCLUSION: Our data indicate that calcitriol, at above physiological serum concentrations, reduces hepatic triglyceride accumulation and glucose output, at least in part through activation of Ca2+/CaMKKbeta/AMPK under insulin-resistant condition. PMID- 27658466 TI - European multicenter study on antimicrobial resistance in bacteria isolated from companion animal urinary tract infections. AB - BACKGROUND: There is a growing concern regarding the increase of antimicrobial resistant bacteria in companion animals. Yet, there are no studies comparing the resistance levels of these organisms in European countries. The aim of this study was to investigate geographical and temporal trends of antimicrobial resistant bacteria causing urinary tract infection (UTI) in companion animals in Europe. The antimicrobial susceptibility of 22 256 bacteria isolated from dogs and cats with UTI was determined. Samples were collected between 2008 and 2013 from 16 laboratories of 14 European countries. The prevalence of antimicrobial resistance of the most common bacteria was determined for each country individually in the years 2012-2013 and temporal trends of bacteria resistance were established by logistic regression. RESULTS: The aetiology of uropathogenic bacteria differed between dogs and cats. For all bacterial species, Southern countries generally presented higher levels of antimicrobial resistance compared to Northern countries. Multidrug-resistant Escherichia coli were found to be more prevalent in Southern countries. During the study period, the level of fluoroquinolone resistant E. coli isolated in Belgium, Denmark, France and the Netherlands decreased significantly. A temporal increase in resistance to amoxicillin clavulanate and gentamicin was observed among E. coli isolates from the Netherlands and Switzerland, respectively. Other country-specific temporal increases were observed for fluoroquinolone-resistant Proteus spp. isolated from companion animals from Belgium. CONCLUSIONS: This work brings new insights into the current status of antimicrobial resistance in bacteria isolated from companion animals with UTI in Europe and reinforces the need for strategies aiming to reduce resistance. PMID- 27658468 TI - Multiobjective guided priors improve the accuracy of near-infrared spectral tomography for breast imaging. AB - An image reconstruction regularization approach for magnetic resonance imaging guided near-infrared spectral tomography has been developed to improve quantification of total hemoglobin (HbT) and water. By combining prior information from dynamic contrast enhanced (DCE) and diffusion weighted (DW) MR images, the absolute bias errors of HbT and water in the tumor were reduced by 22% and 18%, 21% and 6%, and 10% and 11%, compared to that in the no-prior, DCE- or DW-guided reconstructed images in three-dimensional simulations, respectively. In addition, the apparent contrast values of HbT and water were increased in patient image reconstruction from 1.4 and 1.4 (DCE) or 1.8 and 1.4 (DW) to 4.6 and 1.6. PMID- 27658469 TI - Impact of Game-Inspired Infographics on User Engagement and Information Processing in an eHealth Program. AB - BACKGROUND: Online interventions providing individual health behavior assessment should deliver feedback in a way that is both understandable and engaging. This study focused on the potential for infographics inspired by the aesthetics of game design to contribute to these goals. OBJECTIVE: We conducted formative research to test game-inspired infographics against more traditional displays (eg, text-only, column chart) for conveying a behavioral goal and an individual's behavior relative to the goal. We explored the extent to which the display type would influence levels of engagement and information processing. METHODS: Between participants experiments compared game-inspired infographics with traditional formats in terms of outcomes related to information processing (eg, comprehension, cognitive load) and engagement (eg, attitudes toward the information, emotional tone). We randomly assigned participants (N=1162) to an experiment in 1 of 6 modules (tobacco use, alcohol use, vegetable consumption, fruit consumption, physical activity, and weight management). RESULTS: In the tobacco module, a game-inspired format (scorecard) was compared with text-only; there were no differences in attitudes and emotional tone, but the scorecard outperformed text-only on comprehension (P=.004) and decreased cognitive load (P=.006). For the other behaviors, we tested 2 game-inspired formats (scorecard, progress bar) and a traditional column chart; there were no differences in comprehension, but the progress bar outperformed the other formats on attitudes and emotional tone (P<.001 for all contrasts). CONCLUSIONS: Across modules, a game-inspired infographic showed potential to outperform a traditional format for some study outcomes while not underperforming on other outcomes. Overall, findings support the use of game-inspired infographics in behavioral assessment feedback to enhance comprehension and engagement, which may lead to greater behavior change. PMID- 27658470 TI - Direct Oral Anticoagulants in Emergency Trauma Admissions. AB - BACKGROUND: Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery. Clotting disturbances elevate the mortality of such patients to 43%, compared to 17% in patients without a clotting disturbance. This underscores the impor tance of the proper, targeted treatment of trauma patients who are aking DOAC. METHODS: This review is based on articles retrieved by a selective search in PubMed and on a summary of expert opinion and the recommendations of the relevant medical specialty societies. RESULTS: Peak DOAC levels are reached 2-4 hours after the drug is taken. In patients with normal renal and hepatic function, no drug accumulation, and no drug interactions, the plasma level of DOAC 24 hours after administration is generally too low to cause any clinically relevant risk of bleeding. The risk of drug accumulation is higher in patients with renal dysfunction (creatinine clearance [CrCl] of 30 mL/min or less). Dabigatran levels can be estimated from the thrombin time, ecarin clotting time, and diluted thrombin time, while levels of factor Xa inhibitors can be estimated by means of calibrated chromogenic anti factor Xa activity tests. Routine clotting studies do not reliably reflect the anticoagulant activity of DOAC. Surgery should be postponed, if possible, until at least 24-48 hours after the last dose of DOAC. For patients with mild, non life threatening hemorrhage, it suffices to discontinue DOAC; for patients with severe hemorrhage, there are special treatment algorithms that should be followed. CONCLUSION: DOACs in the setting of hemorrhage are a clinical challenge in the traumatological emergency room because of the inadequate validity of the relevant laboratory tests. An emergency antidote is now available only for dabigatran. PMID- 27658471 TI - Fecal Microbiota Transplant in Patients With Recurrent Clostridium Difficile Infection. AB - BACKGROUND: The clinical effectiveness of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridium difficile infections (rCDI) has been demonstrated in randomized controlled trials. To assess the current status of FMT in Germany with respect to active centers, local standards, clinical effectiveness and safety, the MicroTrans Registry (NCT02681068) was established. METHODS: In a long-term retrospective multicenter observational study by the German Clinical Microbiome Study Group (GCMSG), primary and secondary cure on day 30 and 90, as well as occurrence of treatment-related adverse events were assessed. In addition to patient demographic data, we provide an overview of the FMT procedures and techniques used at different centers. RESULTS: Overall, 133 eligible patients from 33 centers were included, of which 64.7% were female (n = 86). The mean age was 75 years (interquartile range: 59.5-81.5). Administration via the duodenal route (n = 59; 44.4%) was the most frequently applied option, followed by colonic (n = 55; 41.1%), capsule (n = 13; 9.8%), and gastric administration (n = 4; 3.0%). Primary cure on day 30 and 90 was achieved in 84.2% (n = 101/120) and 78.3% (n = 72/92) of patients, respectively. Including re treatment, secondary response was achieved in 87.5% (d 30; n = 105/120) and 85.9% (d 90; n = 79/92), respectively. Treatment- elated adverse events were documented in 16 patients (12.0%). CONCLUSION: FMT is a safe and effective treatment option for rCDI. However, FMT is currently available only in few centers in Germany, and treatment options vary from one center to another. PMID- 27658472 TI - The Diagnosis, Treatment, and Follow-up of Renal Cell Carcinoma. AB - BACKGROUND: In 2014, 15 500 persons in Germany were given the diagnosis of renal cell carcinoma. This disease is the third most common cancer of the urogenital system. The mean age at diagnosis is 68 years in men and 71 in men. METHODS: Pertinent publications up to 2014 were retrieved by a systematic literature search and reviewed in a moderated, formalized consensus process. Key questions were generated and answered by the adaptation of existing international guidelines, on the basis of an independent literature review, and by expert consensus. Representatives of 30 medical specialty societies, patient self-help groups, and other organizations participated in the process. RESULTS: The search for guidelines yielded 80 hits, 23 of which were judged by DELBI to be potentially relevant; 7 were chosen for adaptation. Smoking, obesity, and hypertension increase the risk of renal cell carcinoma. Its 5-year survival rate is 75% for men and 77% for women. Renal cell carcinoma accounts for 2.6% of all deaths from cancer in men and 2.1% in women. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in clinical stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain metastases or osseous metastases that are painful or increase the risk of fracture. CONCLUSION: Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress. PMID- 27658473 TI - Propensity Score: an Alternative Method of Analyzing Treatment Effects. AB - BACKGROUND: In intervention trials, only randomization guarantees equal distributions of all known and unknown patient characteristics between an intervention group and a control group and enables causal statements on treatment effects. However, randomized controlled trials have been criticized for insufficient external validity; non-randomized trials are an alternative here, but come with the danger of intervention and control groups differing with respect to known and/or unknown patient characteristics. Non-randomized trials are generally analyzed with multiple regression models, but the so-called propensity score method is now being increasingly used. METHODS: The authors present, explain, and illustrate the propensity score method, using a study on coronary artery bypass surgery as an illustrative example. This article is based on publications retrieved by a selective literature earch and on the authors' scientific experience. RESULTS: The propensity score (PS) is defined as the probability that a patient will receive the treatment under investigation. In a first step, the PS is estimated from the available data, e.g. in a logistic regression model. In a second step, the actual treatment effect is estimated with the aid of the PS. Four methods are available for this task: PS matching, inverse probability of treatment weighting (IPTW), stratification by PS, and regression adjustment for the PS. CONCLUSION: The propensity score method is a good alternative method for the analysis of non-randomized intervention trials, with epistemological advantages over conventional regression modelling. Nonetheless, the propensity score method can only adjust for known confounding factors that have actually been measured. Equal distributions of unknown confounding factors can be achieved only in randomized controlled trials. PMID- 27658474 TI - Blood Pressure and Lifestyle. PMID- 27658475 TI - In Reply. PMID- 27658476 TI - Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter. AB - Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism. PMID- 27658477 TI - Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes. AB - T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence. T-2 toxin has posed various toxic effects on human and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues, while HT-2 toxin is the major metabolite which is deacetylated by T-2 toxin. In this study, we focused on the toxic effects of HT-2 on porcine oocyte maturation. We treated the porcine oocyte with HT-2 toxin in vitro, and we first found that HT-2 treatment inhibited porcine oocyte polar body extrusion and cumulus cell expansion. We observed the disrupted meiotic spindle morphology after treatment, which might be due to the reduced p-MAPK protein level. Actin distribution was also disturbed, indicating that HT-2 affects cytoskeleton of porcine oocytes. We next explored the causes for the failure of oocyte maturation after HT-2 treatment. We found that HT-2 treated oocytes showed the increased ROS level, which indicated that oxidative stress had occurred. We also detected autophagy as well as early apoptosis in the treatment oocytes. Due to the fact that oxidative stress could induced apoptosis, our results indicated that HT-2 toxin caused oxidative stress induced apoptosis and autophagy, which further affected porcine oocyte maturation. PMID- 27658478 TI - Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template. AB - The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (>=90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated. PMID- 27658480 TI - Transmembrane Helices Tilt, Bend, Slide, Torque, and Unwind between Functional States of Rhodopsin. AB - The seven-helical bundle of rhodopsin and other G-protein coupled receptors undergoes structural rearrangements as the transmembrane receptor protein is activated. These structural changes are known to involve tilting and bending of various transmembrane helices. However, the cause and effect relationship among structural events leading to a cytoplasmic crevasse for G-protein binding is less well defined. Here we present a mathematical model of the protein helix and a simple procedure to determine multiple parameters that offer precise depiction of a helical conformation. A comprehensive survey of bovine rhodopsin structures shows that the helical rearrangements during the activation of rhodopsin involve a variety of angular and linear motions such as torsion, unwinding, and sliding in addition to the previously reported tilting and bending. These hitherto undefined motion components unify the results obtained from different experimental approaches, and demonstrate conformational similarity between the active opsin structure and the photoactivated structures in crystallo near the retinal anchor despite their marked differences. PMID- 27658479 TI - Degradable Organically-Derivatized Polyoxometalate with Enhanced Activity against Glioblastoma Cell Line. AB - High efficacy and low toxicity are critical for cancer treatment. Polyoxometalates (POMs) have been reported as potential candidates for cancer therapy. On accounts of the slow clearance of POMs, leading to long-term toxicity, the clinical application of POMs in cancer treatment is restricted. To address this problem, a degradable organoimido derivative of hexamolybdate is developed by modifying it with a cleavable organic group, leading to its degradation. Of note, this derivative exhibits favourable pharmacodynamics towards human malignant glioma cell (U251), the ability to penetrate across blood brain barrier and low toxicity towards rat pheochromocytoma cell (PC12). This line of research develops an effective POM-based agent for glioblastoma inhibition and will pave a new way to construct degradable anticancer agents for clinical cancer therapy. PMID- 27658481 TI - Systematical Evaluation of Mechanically Strong 3D Printed Diluted magnesium Doping Wollastonite Scaffolds on Osteogenic Capacity in Rabbit Calvarial Defects. AB - Wollastonite (CaSiO3; CSi) ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs in vivo. In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi (CSi-Mgx, x = 6, 10, 14) can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60-63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6-12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects. PMID- 27658482 TI - Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti acetylcholinesterase Activities. AB - Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 MUM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary. PMID- 27658483 TI - A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence. AB - Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM-IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2-12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients. PMID- 27658484 TI - Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. AB - 3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance and the beta-keto analog of 3,4-methylenedioxy-N-methylamphetamine (MDMA). It is well established that MDMA metabolism produces bioactive metabolites. Here we tested the hypothesis that methylone metabolism in rats can form bioactive metabolites. First, we examined the pharmacokinetics (PKs) of methylone and its metabolites after subcutaneous (sc) methylone administration (3, 6, 12 mg/kg) to male rats fitted with intravenous (iv) catheters for repeated blood sampling. Plasma specimens were assayed by liquid chromatography tandem mass spectrometry to quantify methylone and its phase I metabolites: 3,4-methylenedioxycathinone (MDC), 3,4-dihydroxy-N-methylcathinone (HHMC), and 4-hydroxy-3-methoxy-N methylcathinone (HMMC). The biological activity of methylone and its metabolites was then compared using in vitro transporter assays and in vivo microdialysis in rat nucleus accumbens. For the PK study, we found that methylone and MDC peaked early (Tmax=15-45 min) and were short lived (t1/2=60-90 min), while HHMC and HMMC peaked later (Tmax=60-120 min) and persisted (t1/2=120-180 min). Area-under-the curve values for methylone and MDC were greater than dose-proportional, suggesting non-linear accumulation. Methylone produced significant locomotor activation, which was correlated with plasma methylone, MDC, and HHMC concentrations. Methylone, MDC, and HHMC were substrate-type releasers at monoamine transporters as determined in vitro, but only methylone and MDC (1, 3 mg/kg, iv) produced significant elevations in brain extracellular dopamine and 5 HT in vivo. Our findings demonstrate that methylone is extensively metabolized in rats, but MDC is the only centrally active metabolite that could contribute to overall effects of the drug in vivo. PMID- 27658485 TI - Sex as a Biological Variable: Who, What, When, Why, and How. AB - The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience. PMID- 27658486 TI - Trace Amine-Associated Receptor 1 Regulates Wakefulness and EEG Spectral Composition. AB - Trace amine-associated receptor 1 (TAAR1) agonists have been shown to have procognitive, antipsychotic-like, anxiolytic, weight-reducing, glucose-lowering, and wake-promoting activities. We used Taar1 knockout (KO) and overexpressing (OE) mice and TAAR1 agonists to elucidate the role of TAAR1 in sleep/wake. EEG, EMG, body temperature (Tb), and locomotor activity (LMA) were recorded in Taar1 KO, OE, and WT mice. Following a 24 h recording to characterize basal sleep/wake parameters, mice were sleep deprived (SD) for 6 h. In another experiment, mice were given three doses of the TAAR1 partial agonist RO5263397, caffeine, or vehicle p.o. Baseline wakefulness was modestly increased in OE compared with WT mice. Baseline theta (4.5-9 Hz) and low gamma (30-60 Hz) activity was elevated in KO compared with OE mice in NREM and REM sleep. Following SD, both KO and OE mice exhibited a homeostatic sleep rebound. In WT mice, RO5263397 increased waking and reduced NREM and REM sleep, decreased gamma power during wake and NREM, and decreased Tb without affecting LMA; these effects were absent in KO mice and potentiated in OE mice. In contrast, caffeine increased wake time, NREM gamma power, and LMA in all strains compared with vehicle; this effect was attenuated in KO and potentiated in OE mice. TAAR1 overexpression modestly increases wakefulness, whereas TAAR1 partial agonism increases wakefulness and also reduces NREM and also REM sleep. These results indicate a modulatory role for TAAR1 in sleep/wake and cortical activity and suggest TAAR1 as a novel target for wake promoting therapeutics. PMID- 27658488 TI - In the linear quadratic model, the Poisson approximation and the Zaider-Minerbo formula agree on the ranking of tumor control probabilities, up to a critical cell birth rate. AB - PURPOSE: To provide a rule for the agreement or disagreement of the Poisson approximation (PA) and the Zaider-Minerbo formula (ZM) on the ranking of treatment alternatives in terms of tumor control probability (TCP) in the linear quadratic model. MATERIALS AND METHODS: A general criterion involving a critical cell birth rate was formally derived. For demonstration, the criterion was applied to a distinct radiobiological model of fast growing head and neck tumors and a respective range of 22 conventional and nonconventional head and neck schedules. RESULTS: There is a critical cell birth rate bcrit below which PA and ZM agree on which one out of two alternative treatment schemes with single-cell survival curves S'(t) and S''(t) offers better TCP: [Formula: see text] For cell birth rates b above this critical cell birth rate, PA and ZM disagree if and only if b >bcrit > 0. In case of the exemplary head and neck schedules, out of 231 possible combinations, only 16 or 7% were found where PA and ZM disagreed. In all 231 cases the prediction of the criterion was numerically confirmed, and cell birth rates at crossovers between schedules matched the calculated critical cell birth rates. CONCLUSIONS: TCP estimated by PA and ZM almost never numerically coincide. Still, in many cases both formulas at least agree about which one out of two alternative fractionation schemes offers better TCP. In case of fast growing tumors featuring a high cell birth rate, however, ZM may suggest a re evaluation of treatment options. PMID- 27658489 TI - "I feel like I am surviving the health care system": understanding LGBTQ health in Nova Scotia, Canada. AB - BACKGROUND: Currently, there is a dearth of baseline data on the health of lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations in the province of Nova Scotia, Canada. Historically, LGBTQ health research has tended to focus on individual-level health risks associated with poor health outcomes among these populations, which has served to obscure the ways in which they maintain their own health and wellness across the life course. As such, there is an urgent need to shift the focus of LGBTQ health research towards strengths based perspectives that explore the complex and resilient ways in which LGBTQ populations promote their health. METHODS: This paper discusses the findings of our recent scoping review as well as the qualitative data to emerge from community consultations aimed at developing strengths-based approaches to understanding and advancing LGBTQ pathways to health across Nova Scotia. RESULTS: Our scoping review findings demonstrated the lack of strengths-based research on LGBTQ health in Nova Scotia. Specifically, the studies examined in our scoping review identified a number of health-promoting factors and a wide variety of measurement tools, some of which may prove useful for future strengths-based health research with LGBTQ populations. In addition, our community consultations revealed that many participants had negative experiences with health care systems and services in Nova Scotia. However, participants also shared a number of factors that contribute to LGBTQ health and suggestions for how LGBTQ pathways to health in Nova Scotia can be improved. CONCLUSIONS: There is an urgent need to conduct research on the health needs, lived experiences, and outcomes of LGBTQ populations in Nova Scotia to address gaps in our knowledge of their unique health needs. In moving forward, it is important that future health research take an intersectional, strengths-based perspective in an effort to highlight the factors that promote LGBTQ health and wellness across the life course, while taking into account the social determinants of health. PMID- 27658490 TI - Electrohydrodynamic printing for scalable MoS2 flake coating: application to gas sensing device. AB - Scalable sub-micrometer molybdenum disulfide ([Formula: see text]) flake films with highly uniform coverage were created using a systematic approach. An electrohydrodynamic (EHD) printing process realized a remarkably uniform distribution of exfoliated [Formula: see text] flakes on desired substrates. In combination with a fast evaporating dispersion medium and an optimal choice of operating parameters, the EHD printing can produce a film rapidly on a substrate without excessive agglomeration or cluster formation, which can be problems in previously reported liquid-based continuous film methods. The printing of exfoliated [Formula: see text] flakes enabled the fabrication of a gas sensor with high performance and reproducibility for [Formula: see text] and [Formula: see text]. PMID- 27658487 TI - Cellular senescence in aging and osteoarthritis. AB - - It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population. PMID- 27658493 TI - Screening ABL1 kinase domain mutations in patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). PMID- 27658491 TI - Tocilizumab as monotherapy or combination therapy for treating active rheumatoid arthritis: a meta-analysis of efficacy and safety reported in randomized controlled trials. AB - BACKGROUND: Previous studies in patients with rheumatoid arthritis (RA) have shown that switching to tocilizumab (TCZ) monotherapy (TCZMONO) or combination therapy (TCZCOMBI) with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is efficacious in reducing disease activity in patients with inadequate response to csDMARDs. However, hitherto there is no consensus on whether TCZMONO is as effective as TCZCOMBI. The objective of this study was therefore to evaluate the efficacy and safety of TCZMONO versus add-on TCZCOMBI and both TCZ therapies versus continuing the current csDMARD therapy, by performing a systematic review and meta-analyses. METHOD: The MEDLINE, EMBASE and CENTRAL databases were searched until February 2016 for relevant randomized controlled trials (RCTs). We performed meta-analyses of Disease Activity Score in 28 joints (DAS28 < 2.6), American College of Rheumatology (ACR) 20/50/70 responses, adverse events (AEs) and serious AEs (SAEs) to compare the three different strategies, whereas a random-effect model was used for pooling relative risks (RR) and 95 % confidence intervals (CI). In addition, sensitivity analyses were performed for evaluating differences in study duration. RESULTS: In total, 13 RCTs were included in the meta-analysis, involving 6679 patients. When comparing both TCZ strategies, a marginally greater proportion of patients achieving DAS28 < 2.6 (RR 1.21; 95 % CI 1.09, 1.36) and ACR50 response (RR 1.14; 95 % CI 1.03, 1.26) was found in favor of the TCZCOMBI strategy. However, the risk of SAEs was also significantly higher using this strategy (RR 1.40; 95 % CI 1.03, 1.92, p = 0.03). Pooled effect estimates showed statistical superiority of switching to either TCZ strategy compared to continuing csDMARD therapy. CONCLUSIONS: In the management of active RA, almost similar efficacy can be expected in patients unable to tolerate csDMARDs, who switch to TCZMONO compared to inadequate responders switching to add-on TCZCOMBI. Although TCZCOMBI is marginally superior to TCZMONO in achieving DAS28 < 2.6 and ACR50 response, this is at the cost of an increased risk of SAEs. PMID- 27658494 TI - Extraction of total nucleic acids from bacterial isolates using the bioMerieux NucliSENS easyMAG total nucleic acid extractor. AB - The BioMerieux NucliSENS easyMAG total nucleic acid extractor was evaluated for use on bacterial isolates in the clinical microbiology laboratory. Forty eight isolates were extracted, yielding quantifiable amounts of DNA for all isolates. The easyMAG is appropriate for DNA extraction from bacterial isolates and will be incorporated in the clinical laboratory. PMID- 27658492 TI - Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients. AB - BACKGROUND: While programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity in a proportion of patients with advanced bladder cancer, strongly predictive and prognostic biomarkers are still lacking. In this study, we evaluated PD-L1 protein expression on circulating tumor cells (CTCs) isolated from patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer and explore the prognostic value of CTC PD-L1 expression on clinical outcomes. METHODS: Blood samples from 25 patients with MIBC or mBCa were collected at UCSF and shipped to Epic Sciences. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC identification by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK)+ and (CK)-CTCs (CD45-, intact nuclei, morphologically distinct from WBCs) were enumerated. A subset of patient samples underwent genetic characterization by fluorescence in situ hybridization (FISH) and copy number variation (CNV) analysis. RESULTS: CTCs were detected in 20/25 (80 %) patients, inclusive of CK+ CTCs (13/25, 52 %), CK-CTCs (14/25, 56 %), CK+ CTC Clusters (6/25, 24 %), and apoptotic CTCs (13/25, 52 %). Seven of 25 (28 %) patients had PD-L1+ CTCs; 4 of these patients had exclusively CK-/CD45-/PD-L1+ CTCs. A subset of CTCs were secondarily confirmed as bladder cancer via FISH and CNV analysis, which revealed marked genomic instability. Although this study was not powered to evaluate survival, exploratory analyses demonstrated that patients with high PD-L1+/CD45 CTC burden and low burden of apoptotic CTCs had worse overall survival. CONCLUSIONS: CTCs are detectable in both MIBC and mBCa patients. PD-L1 expression is demonstrated in both CK+ and CK-CTCs in patients with mBCa, and genomic analysis of these cells supports their tumor origin. Here we demonstrate the ability to identify CTCs in patients with advanced bladder cancer through a minimally invasive process. This may have the potential to guide checkpoint inhibitor immune therapies that have been established to have activity, often with durable responses, in a proportion of these patients. PMID- 27658495 TI - The use of XFEM to assess the influence of intra-cortical porosity on crack propagation. AB - This study aimed at using eXtended finite element method (XFEM) to characterize crack growth through bone's intra-cortical pores. Two techniques were compared using Abaqus: (1) void material properties were assigned to pores; (2) multiple enrichment regions with independent crack-growth possibilities were employed. Both were applied to 2D models of transverse images of mouse bone with differing porous structures. Results revealed that assigning multiple enrichment regions allows for multiple cracks to be initiated progressively, which cannot be captured when the voids are filled. Therefore, filling pores with one enrichment region in the model will not create realistic fracture patterns in Abaqus-XFEM. PMID- 27658496 TI - Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. AB - BACKGROUND: Breast cancer is one of the leading cause of cancer-related deaths in women worldwide and increasing rapidly in developing countries. In the present study, we investigated the potential role and association of HSP70-2 with breast cancer. METHODS: HSP70-2 expression was examined in 154 tumor and 103 adjacent non-cancerous tissue (ANCT) specimens and breast cancer cell lines (MCF7, BT-474, SK-BR-3 and MDA-MB-231) by RT-PCR, quantitative-PCR, immunohistochemistry, Western blotting, flow cytometry and indirect immunofluorescence. Plasmid driven short hairpin RNA approach was employed to validate the role of HSP70-2 in cellular proliferation, senescence, migration, invasion and tumor growth. Further, we studied the effect of HSP70-2 protein ablation on signaling cascades involved in apoptosis, cell cycle and Epithelial-Mesenchymal-Transition both in culture as well as in-vivo human breast xenograft mouse model. RESULTS: HSP70-2 expression was detected in majority of breast cancer patients (83 %) irrespective of various histotypes, stages and grades. HSP70-2 expression was also observed in all breast cancer cells (BT-474, MCF7, MDA-MB-231 and SK-BR-3) used in this study. Depletion of HSP70-2 in MDA-MB-231 and MCF7 cells resulted in a significant reduction in cellular growth, motility, onset of apoptosis, senescence, cell cycle arrest as well as reduction of tumor growth in the xenograft model. At molecular level, down-regulation of HSP70-2 resulted in reduced expression of cyclins, cyclin dependent kinases, anti-apoptotic molecules and mesenchymal markers and enhanced expression of CDK inhibitors, caspases, pro apoptotic molecules and epithelial markers. CONCLUSIONS: HSP70-2 is over expressed in breast cancer patients and was involved in malignant properties of breast cancer. This suggests HSP70-2 may be potential candidate molecule for development of better breast cancer treatment. PMID- 27658497 TI - An innovative masticatory efficiency test using odour intensity in the mouth as a target marker: a feasibility study. AB - A large number of studies have reported the findings for masticatory efficiency tests; however, some objective masticatory efficiency tests have a drawback, in that subjects are required to spit out the test material. This study examined the possibility of a masticatory efficiency test that evaluates the intensity of odours released when chewing an odour compound-containing material. A total of 20 volunteers were used in this study. The odour intensity in the breath after chewing a gum was measured by portable odour sensor device. The odour intensity after chewing the gum was measured over four chewing durations and at four intervals between spitting out and measurement of the odour intensity. The volume of stimulated saliva was measured by calculating the difference in the weight of the gauze before and after chewing to examine the effect of saliva flow. With an increase in chewing duration, odour intensity reduced. The odour intensity was the highest immediately after chewing. There was a positive correlation between odour intensity and gummy jelly-related masticatory efficiency test value (G METV), which was significant for 10-s chewing. The regression equation was calculated from three objective variables of odour intensity and G-METV as dependent variable. Pearson's correlation coefficient between G-METV and the odour intensity-related masticatory efficiency value (O-METV) was 0.68. The coefficient of variation of O-METV was significantly lower than that of G-METV. These results suggest that the masticatory performance can be estimated by measuring the odour intensity immediately after chewing food containing odour compounds for 10 s. PMID- 27658498 TI - Linked Patient-Reported Outcomes Data From Patients With Multiple Sclerosis Recruited on an Open Internet Platform to Health Care Claims Databases Identifies a Representative Population for Real-Life Data Analysis in Multiple Sclerosis. AB - BACKGROUND: An enormous amount of information relevant to public health is being generated directly by online communities. OBJECTIVE: To explore the feasibility of creating a dataset that links patient-reported outcomes data, from a Web-based survey of US patients with multiple sclerosis (MS) recruited on open Internet platforms, to health care utilization information from health care claims databases. The dataset was generated by linkage analysis to a broader MS population in the United States using both pharmacy and medical claims data sources. METHODS: US Facebook users with an interest in MS were alerted to a patient-reported survey by targeted advertisements. Eligibility criteria were diagnosis of MS by a specialist (primary progressive, relapsing-remitting, or secondary progressive), >=12-month history of disease, age 18-65 years, and commercial health insurance. Participants completed a questionnaire including data on demographic and disease characteristics, current and earlier therapies, relapses, disability, health-related quality of life, and employment status and productivity. A unique anonymous profile was generated for each survey respondent. Each anonymous profile was linked to a number of medical and pharmacy claims datasets in the United States. Linkage rates were assessed and survey respondents' representativeness was evaluated based on differences in the distribution of characteristics between the linked survey population and the general MS population in the claims databases. RESULTS: The advertisement was placed on 1,063,973 Facebook users' pages generating 68,674 clicks, 3719 survey attempts, and 651 successfully completed surveys, of which 440 could be linked to any of the claims databases for 2014 or 2015 (67.6% linkage rate). Overall, no significant differences were found between patients who were linked and not linked for educational status, ethnicity, current or prior disease-modifying therapy (DMT) treatment, or presence of a relapse in the last 12 months. The frequencies of the most common MS symptoms did not differ significantly between linked patients and the general MS population in the databases. Linked patients were slightly younger and less likely to be men than those who were not linkable. CONCLUSIONS: Linking patient-reported outcomes data, from a Web-based survey of US patients with MS recruited on open Internet platforms, to health care utilization information from claims databases may enable rapid generation of a large population of representative patients with MS suitable for outcomes analysis. PMID- 27658499 TI - Hemoglobin glutamer-250 (bovine) in South Africa: consensus usage guidelines from clinician experts who have treated patients. AB - Hemopure (hemoglobin glutamer-250 [bovine]; HBOC-201) is a hemoglobin (Hb)-based oxygen carrier registered with the Medicines Control Council of South Africa. It is indicated for the treatment of adult patients who are acutely anemic, for the purpose of maintaining tissue oxygen delivery thus eliminating, delaying, or reducing the need for allogeneic red blood cells (RBCs). Hemopure is a volume expander, and circulatory volume must be carefully monitored for signs of fluid overload. Hemopure is not as effective as RBCs for restoring Hb content and concentration, but in cases of severe anemia where allogeneic blood is not an option or is unavailable, it may offer an immediate alternative for improving oxygen transport. This document provides clinical recommendations on the safe and effective use of Hemopure based on the postmarketing experience in South Africa as well as a better understanding of Hemopure properties reflected in recent publications. PMID- 27658500 TI - Prevalence of systemic anticancer therapy for patients within the last 30 days of life: experience in a private hospital oncology group. AB - BACKGROUND: In recent years, there has been a significant increase in the number of cancer treatments that have become available. However, it has remained difficult to choose the most appropriate time to cease active therapy in individual patients. AIMS: To determine the proportion of patients being treated with palliative intent who received systemic anticancer treatment in the last 30 days of life. METHODS: This is a retrospective cohort study conducted within the Melbourne Oncology Group at Cabrini Hospital. Patients managed with palliative intent who died between 1 January 2014 and 30 June 2014 were included. Outcomes measured were the percentage of patients who received systemic anticancer treatment in the last 30 days of life, palliative care referral status, Emergency Department presentations, hospital admissions and place of death. RESULTS: A total of 80 patients was included in the study. Of these patients, 21 (26%) received systemic anticancer treatment in the last 30 days of life. There was no statistically significant difference between patients who received treatment in the last month of life and those who did not in terms of the number of patients who were referred to palliative care, presented to an Emergency Department, were admitted to hospital or died in an acute ward. CONCLUSION: Although over a quarter of patients dying from advanced cancer received anticancer treatment in the last month of life, these patients did not present acutely to hospital more often and had the same extent of palliative care team involvement. PMID- 27658501 TI - A first report of East Asian students' perception of progress testing: a focus group study. AB - BACKGROUND: Progress testing (PT) is used in Western countries to evaluate students' level of functional knowledge, and to enhance meaning-oriented and self directed learning. However, the use of PT has not been investigated in East Asia, where reproduction-oriented and teacher-centered learning styles prevail. Here, we explored the applicability of PT by focusing on student perceptions. METHODS: Twenty-four students from Years 2, 3, and 5 at Jichi Medical University in Japan attended a pilot PT session preceded by a brief introduction of its concept and procedures. Variations in obtained test scores were analyzed by year, and student perceptions of PT were explored using focus groups. RESULTS: Formula scores (mean +/- standard deviation) in Years 2, 3, and 5 were 12.63 +/- 3.53, 35.88 +/- 14.53, and 71.00 +/- 18.31, respectively. Qualitative descriptive analysis of focus group data showed that students disfavored testing of medical knowledge without tangible goals, but instead favored repetitive assessment of knowledge that had been learned and was tested on a unit basis in the past in order to achieve deep learning. Further, students of all school years considered that post test explanatory lectures by teachers were necessary. CONCLUSIONS: East Asian students' perceptions indicated that, in addition to their intensive memorization within narrow test domains compartmentalized by end-of-unit tests, the concept of PT was suitable for repetitive memorization, as it helped them to integrate their knowledge and to increase their understanding. Post-test explanatory lectures might lessen their dislike of the intangible goals of PT, but at the expense of delaying the development of self-directed learning. Key issues for the optimization of PT in East Asia may include administration of PT after completed end-of-unit tests and a gradual change in feedback methodology over school years from test-oriented post-test lectures to the provision of literature references only, as a means of enhancing test self-review and self-directed learning. PMID- 27658502 TI - Use of molecular markers to improve relationship information in the genetic evaluation of beef cattle tick resistance under pedigree-based models. AB - The selection of genetically superior individuals is conditional upon accurate breeding value predictions which, in turn, are highly depend on how precisely relationship is represented by pedigree. For that purpose, the numerator relationship matrix is essential as a priori information in mixed model equations. The presence of pedigree errors and/or the lack of relationship information affect the genetic gain because it reduces the correlation between the true and estimated breeding values. Thus, this study aimed to evaluate the effects of correcting the pedigree relationships using single-nucleotide polymorphism (SNP) markers on genetic evaluation accuracies for resistance of beef cattle to ticks. Tick count data from Hereford and Braford cattle breeds were used as phenotype. Genotyping was carried out using a high-density panel (BovineHD - Illumina(r) bead chip with 777 962 SNPs) for sires and the Illumina BovineSNP50 panel (54 609 SNPs) for their progenies. The relationship between the parents and progenies of genotyped animals was evaluated, and mismatches were based on the Mendelian conflicts counts. Variance components and genetic parameters estimates were obtained using a Bayesian approach via Gibbs sampling, and the breeding values were predicted assuming a repeatability model. A total of 460 corrections in relationship definitions were made (Table 1) corresponding to 1018 (9.5%) tick count records. Among these changes, 97.17% (447) were related to the sire's information, and 2.8% (13) were related to the dam's information. We observed 27.2% (236/868) of Mendelian conflicts for sire-progeny genotyped pairs and 14.3% (13/91) for dam-progeny genotyped pairs. We performed 2174 new definitions of half-siblings according to the correlation coefficient between the coancestry and molecular coancestry matrices. It was observed that higher-quality genetic relationships did not result in significant differences of variance components estimates; however, they resulted in more accurate breeding values predictions. Using SNPs to assess conflicts between parents and progenies increases certainty in relationships and consequently the accuracy of breeding value predictions of candidate animals for selection. Thus, higher genetic gains are expected when compared to the traditional non-corrected relationship matrix. PMID- 27658503 TI - Large venous malformation of right colonic flexure. PMID- 27658504 TI - Massive thyroid goiter: an unusual cause of aspiration pneumonia. PMID- 27658505 TI - Implementation of pattern-mixture models in randomized clinical trials. AB - Modern analysis of incomplete longitudinal outcomes involves formulating assumptions about the missingness mechanisms and then using a statistical method that produces valid inferences under this assumption. In this manuscript, we define missingness strategies for analyzing randomized clinical trials (RCTs) based on plausible clinical scenarios. Penalties for dropout are also introduced in an attempt to balance benefits against risks. Some missingness mechanisms are assumed to be non-future dependent, which is a subclass of missing not at random. Non-future dependent stipulates that missingness depends on the past and the present information but not on the future. Missingness strategies are implemented in the pattern-mixture modeling framework using multiple imputation (MI), and it is shown how to estimate the marginal treatment effect. Next, we outline how MI can be used to investigate the impact of dropout strategies in subgroups of interest. Finally, we provide the reader with some points to consider when implementing pattern-mixture modeling-MI analyses in confirmatory RCTs. The data set that motivated our investigation comes from a placebo-controlled RCT design to assess the effect on pain of a new compound. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27658507 TI - Dyspnea in a case of shoulder dislocation - to beware of this rare life threatening symptom. AB - Shoulder dislocation is a common injury in orthopedic practice. In an acute presentation, closed reduction of the shoulder joint leads to an uneventful recovery. However, in the developing world neglected shoulder dislocation and treatments from quacks are not uncommon. Improper treatment and neglect can rarely become life threatening. We present one such case, emphasizing the need to investigate the symptom of dyspnea in a patient with history of shoulder dislocation. PMID- 27658506 TI - Comparison of spoiled gradient echo and steady-state free-precession imaging for native myocardial T1 mapping using the slice-interleaved T1 mapping (STONE) sequence. AB - Cardiac T1 mapping allows non-invasive imaging of interstitial diffuse fibrosis. Myocardial T1 is commonly calculated by voxel-wise fitting of the images acquired using balanced steady-state free precession (SSFP) after an inversion pulse. However, SSFP imaging is sensitive to B1 and B0 imperfection, which may result in additional artifacts. A gradient echo (GRE) imaging sequence has been used for myocardial T1 mapping; however, its use has been limited to higher magnetic field to compensate for the lower signal-to-noise ratio (SNR) of GRE versus SSFP imaging. A slice-interleaved T1 mapping (STONE) sequence with SSFP readout (STONE SSFP) has been recently proposed for native myocardial T1 mapping, which allows longer recovery of magnetization (>8 R-R) after each inversion pulse. In this study, we hypothesize that a longer recovery allows higher SNR and enables native myocardial T1 mapping using STONE with GRE imaging readout (STONE-GRE) at 1.5T. Numerical simulations and phantom and in vivo imaging were performed to compare the performance of STONE-GRE and STONE-SSFP for native myocardial T1 mapping at 1.5T. In numerical simulations, STONE-SSFP shows sensitivity to both T2 and off resonance. Despite the insensitivity of GRE imaging to T2 , STONE-GRE remains sensitive to T2 due to the dependence of the inversion pulse performance on T2 . In the phantom study, STONE-GRE had inferior accuracy and precision and similar repeatability as compared with STONE-SSFP. In in vivo studies, STONE-GRE and STONE-SSFP had similar myocardial native T1 times, precisions, repeatabilities and subjective T1 map qualities. Despite the lower SNR of the GRE imaging readout compared with SSFP, STONE-GRE provides similar native myocardial T1 measurements, precision, repeatability, and subjective image quality when compared with STONE SSFP at 1.5T. PMID- 27658508 TI - Entanglement and nonclassicality in four-mode Gaussian states generated via parametric down-conversion and frequency up-conversion. AB - Multipartite entanglement and nonclassicality of four-mode Gaussian states generated in two simultaneous nonlinear processes involving parametric down conversion and frequency up-conversion are analyzed assuming the vacuum as the initial state. Suitable conditions for the generation of highly entangled states are found. Transfer of the entanglement from the down-converted modes into the up converted ones is also suggested. The analysis of the whole set of states reveals that sub-shot-noise intensity correlations between the equally-populated down converted modes, as well as the equally-populated up-converted modes, uniquely identify entangled states. They represent a powerful entanglement identifier also in other cases with arbitrarily populated modes. PMID- 27658510 TI - Purinergic Signalling and Neurological Diseases: An Update. AB - Purinergic signalling, i.e. ATP as an extracellular signalling molecule and cotransmitter in both peripheral and central neurons, is involved in the physiology of neurotransmission and neuromodulation. Receptors for purines have been cloned and characterised, including 4 subtypes of the P1(adenosine) receptor family, 7 subtypes of the P2X ion channel nucleotide receptor family and 8 subtypes of the P2Y G protein-coupled nucleotide receptor family. The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field about the involvement of purinergic signalling in Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis, amyotrophic lateral sclerosis, degeneration and regeneration after brain injury, stroke, ischaemia, inflammation, migraine, epilepsy, psychiatric disorders, schizophrenia, bipolar disorder, autism, addiction, sleep disorders and brain tumours. The use in particular of P2X7 receptor antagonists for the treatment of neurodegenerative diseases, cancer, depression, stroke and ischaemia, A2A receptor antagonists for Parkinson's disease and agonists for brain injury and depression and P2X3 receptor antagonists for migraine and seizures has been recommended. P2Y receptors have also been claimed to be involved in some central nervous disorders. PMID- 27658511 TI - An Overview on the Role of alpha -Synuclein in Experimental Models of Parkinson's Disease from Pathogenesis to Therapeutics. AB - Parkinson's disease (PD) is a devastating and progressive movement disorder characterized by symptoms of muscles rigidity, tremor, postural instability and slow physical movements. Biochemically, PD is characterized by lack of dopamine production and its action due to loss of dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as Lewy bodies, which mainly consist of presynaptic neuronal protein, alpha-synuclein (alpha-syn). It is believed that alteration in alpha-syn homeostasis leads to increased accumulation and aggregation of alpha-syn in Lewy body. Based on the important role of alpha-syn from pathogenesis to therapeutics, the recent researches are mainly focused on deciphering the critical role of alpha-syn at advanced level. Being a major protein in Lewy body that has a key role in pathogenesis of PD, several model systems including immortalized cell lines (SH SY5Y), primary neuronal cultures, yeast (saccharomyces cerevisiae), drosophila (fruit flies), nematodes (Caenorhabditis elegans) and rodents are being employed to understand the PD pathogenesis and treatment. In order to study the etiopathogensis and develop novel therapeutic target for alpha -syn aggregation, majority of investigators rely on toxin (rotenone, 1-Methyl-4-Phenyl-1,2,3,6 Tetrahydropyridine, 6-hydroxydopamine, paraquat)-induced animal models of PD as a tool for basic research. Whereas, cell and tissue based models are mostly utilized to elucidate the mechanistic and molecular pathways underlying the alpha -syn induced toxicity and therapeutic approaches in PD. Gene modified mouse models based on alpha-syn expression are fascinating for modeling familial PD and toxin induced models provide a suitable approach for sporadic PD. The purpose of this review is to provide a summary and a critical review of the involvement of alpha-syn in various in vitro and in vivo models of PD based on use of neurotoxins as well as genetic modifications. PMID- 27658512 TI - Involvement of the Blood-Brain Barrier in Metabolic Regulation. AB - Pertinent to pandemic obesity, the discovery of endogenous peptides that affect the ingestion of food has led to the question of how these ingestive peptides exert their actions in the brain. Whereas peripheral sources provide a ready reserve, the availability of ingestive peptides to their central nervous system targets can be regulated by the blood-brain barrier (BBB). Some of the peptides/polypeptides are transported by saturable mechanisms from blood to brain. Examples include leptin, insulin, mahogany, and pancreatic polypeptide. Some enter the brain by passive diffusion, such as neuropeptide Y, orexin A, cocaine- and amphetamine-regulated transcript, cyclo His-Pro, and amylin. Some others may have essentially no penetration of the BBB; this class includes agouti related protein, melanin-concentrating hormone, and urocortin. The regulatory function of the BBB can be seen in various physiological states. Hyperglycemia may upregulate transport systems for leptin, urocortin, and galanin-like peptide, whereas fasting can down-regulate those for leptin and galanin-like peptide. Thus, the BBB plays a dynamic role in modulating the passage of ingestive peptides from blood to brain. PMID- 27658509 TI - Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca. AB - BACKGROUND: Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. RESULTS: Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p < 0.0001). CONCLUSIONS: Our results showed that the association of traditional immune-suppressive therapy with the antioxidant/anti-inflammatory properties of the nutraceutical diet resulted in a significant amelioration of clinical signs and symptoms in cKCS. The beneficial effects, likely due to the presence of supplemented nutraceuticals in the diet, appeared to specifically reduce the immune-mediated ocular symptoms in those cKCS affected dogs that were poorly responsive or unresponsive to classical immunosuppressive drugs. These data suggest that metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS. PMID- 27658513 TI - Spinal Cord Injury Changes Cytokine Transport. AB - Here we summarize three aspects of our understanding of the interactions of cytokines and neurotrophic peptides/proteins with the blood-brain and bloodspinal cord barriers (BBB): (a) pharmacokinetic analysis that has been reported for native cytokines and neurotrophic peptides/proteins; (b) landmark work on conjugated proteins to enhance their delivery across the normal BBB; and (c) regulatory changes under pathophysiological conditions in rodents, particularly after spinal cord injury (SCI). First, though the BBB restricts the permeation of large proteins, some cytokines and neurotrophic peptides/proteins in the periphery can reach the central nervous system (CNS) by specific transport systems. Moreover, SCI and some other disease processes may regulate these transport systems. The significance of studies of the transport systems is obvious because of the biological impact of these molecules on the CNS in health and disease. We have characterized the pharmacokinetic characteristics of some stable cytokines and neurotrophic peptides/proteins in mice after intravenous administration and also in the setting of in situ brain perfusion. In the particular case of SCI, there are time- and regionspecific changes of BBB permeability and transport systems. Tumor necrosis factor-alpha, a cytokine with dual actions in regeneration of the spinal cord, has a slow basal influx into the brain and spinal cord. After SCI, the increase in the entry of tumor necrosis factor-alpha to the CNS differs from leakage after BBB disruption and is related to upregulation of the transport system in a unique temporal and regional pattern. Overall, the permeation of cytokines across the BBB can be mediated by specific transport systems. The regulation of transport in pathophysiological conditions affects the extent of neuroinflammation and is implicated in neuroregeneration. PMID- 27658514 TI - 'Non-Criteria' Neurologic Manifestations of Antiphospholipid Syndrome: A Hidden Kingdom to be Discovered. AB - Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS. PMID- 27658515 TI - Effect of Environmental Extremely Low-Frequency Electromagnetic Fields Exposure on Inflammatory Mediators and Serotonin Metabolism in a Human Neuroblastoma Cell Line. AB - Exposure to environmental extremely low-frequency electromagnetic fields (ELF EMF) in everyday life is increasing and it is a matter of great debate whether exposure to ELF-EMF can be harmful to human health. The neuropathology and symptoms of neurodegenerative disease depends on factors other than genetic predispositions, such as environmental exposure to disease-related risk factors. Research focusing on a possible contribution of ELF-EMF to cell injury and to the development of neurodegenerative disorders is characterized by conflicting data from epidemiological and animal studies. Due to lack of a direct link between neurodegenerative processes and ELF-EMF exposure, our goal was to investigate if ELF-EMF exposure may represent a possible risk factor. In the present study, using neuronal-like SH-SY5Y neuroblastoma cells, we show that the balance between generation and elimination of reactive oxygen species, as well as the balance between pro- and anti-inflammatory cytokines linked to oxidative stress, was maintained ensuring that cells respond properly to ELF-EMF (50Hz /1mT). In SH SY5Y-exposed cells we observed increased intracellular 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio reflecting the rate of transmitter synthesis, catabolism and release, while matrix metalloproteinases that play critical roles in neuronal cell death were not significantly altered. The results presented here indicate that changes caused by short (1h-3h) and sub-chronic (48 h) exposure to 50Hz/1mT ELF-EMF in SH-SY5Y cells are minor in comparison to the neuronal cell damage expected to underlie neurodegeneration or cognitive impairment. Thus, these results are in accord with epidemiological studies that have provided little support for a link between ELF-EMFs and neurodegeneration. PMID- 27658517 TI - Endophytes and Neurodegenerative Diseases: A Hope in Desperation. AB - Neurodegeneration is progressive loss of functional and structural integrity of the central nervous system. Neurodegenerative disorders are yet without any reliable therapy because the neurons of the central nervous system have limited ability to regenerate. Current therapeutic approaches rely mainly on abrogation of symptoms and leave the dying neurons to their fate. Protective and/or rescuing treatments need to be explored fully to suppress neuronal death that will automatically alleviate the symptoms. Adequate precedent exists in literature regarding the neuroprotective activity of endophytes. Endophytes are a class of microorganisms which colonize healthy plant tissues without causing any apparent harm to the host. Chemical moieties from known endophytes have been used against many disease models including neurodegenerative diseases. There is great hope that novel bioactive molecules from newer endophytes can impede pathogenic mechanisms and progression of many diseases. In this review, we will discuss promising pharmacological or clinical relevance of endophytes against various neurodegenerative diseases. PMID- 27658516 TI - Breakdown of Blood-Brain and Blood-Spinal Cord Barriers During Acute Methamphetamine Intoxication: Role of Brain Temperature. AB - Methamphetamine (METH) is a powerful and often-abused stimulant with potent addictive and neurotoxic properties. While it is generally believed that structural brain damage induced by METH results from oxidative stress, in this work we present data suggesting robust disruption of blood-brain and blood-spinal cord barriers during acute METH intoxication in rats. We demonstrate the relationships between METH-induced brain hyperthermia and widespread but structure-specific barrier leakage, acute glial cell activation, changes in brain water and ionic homeostasis, and structural damage of different types of cells in the brain and spinal cord. Therefore, METH-induced leakage of the blood-brain and blood-spinal cord barriers is a significant contributor to different types of functional and structural brain abnormalities that determine acute toxicity of this drug and possibly neurotoxicity during its chronic use. PMID- 27658518 TI - Correction: Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta analysis. PMID- 27658519 TI - In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia. AB - BACKGROUND: Teriflunomide, an inhibitor of dihydroorotate dehydrogenase, is thought to ameliorate multiple sclerosis by reducing activation-induced proliferation of lymphocytes, which is highly dependent on de novo pyrimidine synthesis. Nevertheless, its immunomodulatory effects on resident glial cells in the central nervous system are only poorly understood. METHODS: In this study, we employed physiologically relevant concentrations of teriflunomide and investigated its effects on survival, proliferation, activation, and function of primary rat microglia in vitro. RESULTS: We demonstrate that teriflunomide had no cytotoxic effect on microglia and had only a minor impact on microglial activation. In a concentration- and time-dependent manner, teriflunomide significantly downregulated surface expression of the co-stimulatory molecule CD86. Furthermore, in the highest concentration applied (5 MUM), it slightly increased the expression of interleukin-10 in microglia in response to lipopolysaccharide. Treatment with low concentrations of teriflunomide (0.25-1 MUM) did not have any impact on the activation or proliferation of microglia. At 5 MUM concentration of teriflunomide, we observed a reduction of approximately 30 % in proliferation of microglia in mixed glial cell cultures. CONCLUSIONS: Taken together, our in vitro findings suggest that at higher concentrations, teriflunomide potentially exerts its effects by reducing microglial proliferation and not by modulating the M1-/M2-like cell differentiation of primary rat microglia. Thus, teriflunomide has no major impact on the plasticity of microglia; however, the anti-proliferative and minimal anti-inflammatory effects might be clinically relevant for immune modulation in the treatment of neuroinflammatory CNS diseases such as multiple sclerosis. PMID- 27658520 TI - Activation of hypothalamic astrocytes suppresses feeding without altering emotional states. AB - Emerging evidence shows that hypothalamic astrocytes react to and counteract energy surfeit produced by high-fat diet (HFD) feeding. However, the functional role of astrocytes in the control of energy states and the underlying molecular mechanism(s) during physiological conditions remain largely underexplored. In the present study, by taking advantage of spatiotemporally precise optogenetic approaches, real-time measurements of extracellular adenosine, and behavioral assays, we find that optogenetic stimulation of astrocytes localized in the medial basal hypothalamus (MBH) suppresses food intake in a frequency dependent manner with high frequency, but not low frequency, stimulation of astrocytes reducing food intake. Furthermore, stimulation of MBH astrocytes diminishes orexigenic ghrelin or fasting-induced hyperphagia without effecting anxiety related behavior. Consistent with a frequency dependent role for MBH astrocytes in feeding behavior, optogenetic stimulation of MBH astrocytes increases extracellular levels of adenosine in a frequency dependent manner. Collectively, our results provide new insights into the role of astrocytes in physiological functions during naturally occurring behaviors, such as feeding. GLIA 2016;64:2263-2273. PMID- 27658521 TI - A novel testate amoebae trait-based approach to infer environmental disturbance in Sphagnum peatlands. AB - Species' functional traits are closely related to ecosystem processes through evolutionary adaptation, and are thus directly connected to environmental changes. Species' traits are not commonly used in palaeoecology, even though they offer powerful advantages in understanding the impact of environmental disturbances in a mechanistic way over time. Here we show that functional traits of testate amoebae (TA), a common group of palaeoecological indicators, can serve as an early warning signal of ecosystem disturbance and help determine thresholds of ecosystem resilience to disturbances in peatlands. We analysed TA traits from two Sphagnum-dominated mires, which had experienced different kinds of disturbances in the past 2000 years - fire and peat extraction, respectively. We tested the effect of disturbances on the linkages between TA community structure, functional trait composition and functional diversity using structural equation modelling. We found that traits such as mixotrophy and small hidden apertures (plagiostomic apertures) are strongly connected with disturbance, suggesting that these two traits can be used as palaeoecological proxies of peatland disturbance. We show that TA functional traits may serve as a good proxy of past environmental changes, and further analysis of trait-ecosystem relationships could make them valuable indicators of the contemporary ecosystem state. PMID- 27658522 TI - Physician attitudes and experiences with Maryland's prescription drug monitoring program (PDMP). AB - AIMS: Physicians' use of prescription drug monitoring programs (PDMPs) varies by state. Among Maryland physicians, we sought to (1) estimate the PDMP impact on changes in opioid prescribing, (2) approximate the scope of PDMP utility and (3) determine the barriers to PDMP use after its 2013 implementation. DESIGN: Cross sectional postal survey linking responses to state records of PDMP registration and use, randomly sampling physicians within specialty and registration strata. SETTING: Maryland, USA. PARTICIPANTS: A total of 1000 surveyed primary care, pain and emergency medicine physicians stratified into three subpopulations: PDMP non registrants, PDMP registrants who were non-users and PDMP users; 405 respondents (44%) of 916 eligible physicians were analysed. MEASUREMENTS: Primary outcome measure was PDMP use. Key predictors were clinic characteristics, including type of practice and number of patients prescribed opioids. FINDINGS: No response-wave bias was identified. Seventy per cent of physicians believed PDMP access decreased their amount and increased their comfort level in prescribing opioids. Three-fourths (74%) of PDMP users reported the data very useful for informing opioid prescribing, although one-fifth (20%) reported difficulty accessing the data. Commonly reported barriers to PDMP use were lack of knowledge regarding its existence and registration process. In multivariable analysis after adjusting for key clinic characteristics, practicing at a managed care organization was associated with lower PDMP use [incidence rate ratio (IRR) = 0.19, 95% confidence interval (CI) = 0.05-0.73]. Conversely, physicians who prescribed opioids for more than 50 patients accessed the PDMP three times as often as those prescribing opioids for fewer than 10 patients monthly (IRR = 3.00, 95 % CI = 1.07-8.43). CONCLUSIONS: In this survey of Maryland, USA physicians, most participants reported that prescription drug monitoring programs (PDMPs) improved their opioid prescribing by decreasing prescription amounts and increasing comfort with prescribing opioids. Common barriers to PDMP use included not knowing about the program, registration difficulties and data access difficulties. PMID- 27658523 TI - Increased need for interventions predicts mortality in the critically ill. AB - INTRODUCTION: The aim of this study was to determine the association of early treatment intensity with hospital mortality of intensive care unit (ICU) patients. METHODS: We performed an observational study based on a national ICU registry. We included adult patients treated in Finnish ICUs between 2003 and 2013 with the length of ICU stay of more than 3 days. We measured treatment intensity with the Therapeutic Intervention Scoring System (TISS-76). We assessed mean and daily TISS scores. To define the change in treatment intensity during the first days in the ICU, we calculated the difference between the TISS score on day 3 and the score on day 1 (DeltaTISS). We used multivariate logistic regression to adjust for baseline differences and continuous net reclassification improvement (NRI) to determine the impact of adding TISS data to the baseline prediction model on its prognostic performance. RESULTS: We identified 42,493 patients eligible for the study. For 71% of the patients, DeltaTISS was <= 0 and crude hospital mortality was 18%. DeltaTISS > 0 was observed for 29% of the patients, with a hospital mortality of 23%. When compared to the group DeltaTISS <= 0, the category DeltaTISS > 0 was independently associated with substantially increased mortality. Adding TISS data to the prediction model resulted in the improvement of prognostic performance particularly in the patients with the lowest initial baseline risk. CONCLUSIONS: Early increase in TISS scores was associated with increased risk of death, especially in patients with a lower initial severity of illness. PMID- 27658525 TI - Time to lowest postoperative carcinoembryonic antigen level is predictive on survival outcome in rectal cancer. AB - This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline, and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0-18.0) weeks and -67% (range, -99% to 114%) respectively. Patients with TTDpR 4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06-1.22, P = 0.001) and 1.17 (95% CI 1.07-1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03 1.21, P = 0.006) and 1.17 (95% CI 1.06-1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not. PMID- 27658526 TI - Impact of a high Edinburgh Postnatal Depression Scale score on obstetric and perinatal outcomes. AB - The aim of this retrospective study was to characterise intrapartum and neonatal outcomes in women with an antenatally recorded Edinburgh Postnatal Depression Score (EPDS) <= 9 compared with women with a score of >=12 at a major Australian tertiary maternity hospital. Women with scores >=12 are at particularly high risk of major depressive symptomatology. There were 20512 (78.6%) women with a score <= 9 and 2708 (10.4%) had a score >= 12. Category 1 caesarean sections where there was immediate threat to life (maternal or fetal) were more common in women with EPDS scores >=12 (5.2% vs. 4.3%, OR 1.24 95% CI 1.03-1.49, p = 0.024). Pre term birth (<37 weeks) was also more common (11.7% vs. 8.6%, OR 1.38 95% CI 1.21 1.57, p < 0.001). Women with high scores had higher rates of babies with birth weights <5th centile (6.2% vs. 4.4%, p < 0.001). Apgar score < 7 at 5 minutes were more frequent in the high EPDS group (3.1% vs. 2%, OR 1.52 95% CI 1.18-1.93, p < 0.001). Resuscitation at birth (34.4% vs. 30.6%, p < 0.001) and neonatal death (0.48% vs. 0.13%, OR 2.52 95% CI 1.2-5.0, p < 0.001) were higher in babies of these women. These results suggest poorer intrapartum and neonatal outcomes for women with high EPDS scores. PMID- 27658524 TI - Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease. AB - Enzyme replacement therapy (ERT) is the standard of care for several lysosomal storage diseases (LSDs). ERT, however, requires multiple and costly administrations and has limited efficacy. We recently showed that a single high dose administration of adeno-associated viral vector serotype 8 (AAV2/8) is at least as effective as weekly ERT in a mouse model of mucopolysaccharidosis type VI (MPS VI). However, systemic administration of high doses of AAV might result in both cell-mediated immune responses and insertional mutagenesis. Here we evaluated whether the combination of low doses of AAV2/8 with a less frequent (monthly) than canonical (weekly) ERT schedule may be as effective as the single treatments at high doses or frequent regimen. A greater reduction of both urinary glycosaminoglycans, considered a sensitive biomarker of therapeutic efficacy, and storage in the myocardium and heart valves was observed in mice receiving the combined than the single therapies. Importantly, these levels of correction were similar to those we obtained in a previous study following either high doses of AAV2/8 or weekly ERT. Our data show that low-dose gene therapy can be used as a means to rarify ERT administration, thus reducing both the risks and costs associated with either therapies. PMID- 27658527 TI - PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion. AB - PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility. MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths. RESULTS: We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro inflammatory mediators interleukin (IL)-1beta, IL-6, and IL-8 in tendon sheaths. CONCLUSIONS: RabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair. PMID- 27658528 TI - Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. AB - Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb repressive complex 2 (PRC2), has attracted broad research attention in the past few years because of its involvement in the development and maintenance of many types of cancer and the use of specific EZH2 inhibitors in clinical trials. Several observations show that PRC2 can have both oncogenic and tumour suppressive functions. We propose that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes. PMID- 27658531 TI - Tooth wear as a means to quantify intra-specific variations in diet and chewing movements. AB - In mammals, tooth function, and its efficiency, depends both on the mechanical properties of the food and on chewing dynamics. These aspects have rarely been studied in combination and/or at the intra-specific level. Here we applied 3D dental surface texture analysis to a sample of field voles (Microtus agrestis) trapped from Finnish Lapland at different seasons and localities to test for inter-population variations. We also explored intra-individual variation in chewing dynamics by analysing two facets on the second upper molars. Our results confirm that the two localities have similar environments and that the voles feed on the same items there. On the other hand, the texture data suggest that diets are seasonally variable, probably due to varying concentrations of abrasives. Lastly, the textures on the buccal facets are more isotropic and their direction deviates more from the mesial chewing direction than the lingual facets. We interpret these results as reflecting food, rather than chewing, movements, where food particles are more guided on the lingual side of the molars. This has implications for the application of dental microwear analysis to fossils: only homologous facets can be compared, even when the molar row seems to constitute a functional unit. PMID- 27658529 TI - The multifaceted roles of fatty acid synthesis in cancer. AB - Lipid metabolism, in particular the synthesis of fatty acids (FAs), is an essential cellular process that converts nutrients into metabolic intermediates for membrane biosynthesis, energy storage and the generation of signalling molecules. This Review explores how different aspects of FA synthesis promote tumorigenesis and tumour progression. FA synthesis has received substantial attention as a potential target for cancer therapy, but strategies to target this process have not yet translated into clinical practice. Furthermore, efforts to target this pathway must consider the influence of the tumour microenvironment. PMID- 27658532 TI - Postoperative start compared to preoperative start of low-molecular-weight heparin increases mortality in patients with femoral neck fractures. AB - Background and purpose - Controversies exist regarding thromboprophylaxis in orthopedic surgery. Using data in the nationwide Norwegian Hip Fracture Register (NHFR) with postoperative death and reoperation in the first 6 months after surgery as endpoints in the analyses, we determined whether the thromboprophylaxis in patients who undergo hemiarthroplasty for femoral neck fracture should start preoperatively or postoperatively. Patients and methods - After each operation for hip fracture in Norway, the surgeon reports information on the patient, the fracture, and the operation to the NHFR. Cox regression analyses were performed with adjustments for age, ASA score, gender, type of implant, length of surgery, and year of surgery. Results - During the period 2005 2014, 25,019 hemiarthroplasties as treatment for femoral neck fractures were reported to the registry. Antithrombotic medication was given to 99% of the patients. Low-molecular-weight heparin predominated with dalteparin in 57% of the operations and enoxaparin in 41%. Only operations with these 2 drugs and with known information on preoperative or postoperative start of the prophylaxis were included in the analyses (n = 20,241). Compared to preoperative start of thromboprophylaxis, postoperative start of thromboprophylaxis gave a higher risk of death (risk ratio (RR) = 1.13, 95% CI: 1.06-1.21; p < 0.001) and a higher risk of reoperation for any reason (RR =1.19, 95% CI: 1.01-1.40; p = 0.04), whereas we found no effect on reported intraoperative bleeding complication or on the risk of postoperative reoperation due to hematoma. The results did not depend on whether the initial dose of prophylaxis was the full dosage or half of the standard dosage. Interpretation - Postoperative start of thromboprophylaxis increased the mortality and risk of reoperation compared to preoperative start in femoral neck fracture patients operated with hemiprosthesis. The risks of bleeding and of reoperation due to hematoma were similar in patients who received low-molecular-weight heparin preoperatively and in those who received it postoperatively. PMID- 27658534 TI - Quantum efficiency of colloidal suspensions containing quantum dot/silica hybrid particles. AB - We have investigated the fluorescence properties of colloidal suspensions conntaining quantum dot (QD)/silica hybrid particles. First, we synthesized QD/silica hybrid particles with silica-QD-silica (SQS) core-shell-shell geometry, and monitored the quantum efficiencies of their suspensions at various particle concentrations. We found that the quantum efficiency (QE) of SQS particles in deionized (DI) water was much lower than that of the QDs even at low particle concentration, mainly due to the light scattering of emitted photons at the silica/water interface, followed by reabsorption by QDs. As the concentration of SQS particles was increased, both light scattering and reabsorption by QDs became more important, which further reduced the QE. Refractive index-matched solvent, however, reduced light scattering, yielding greater QE than DI water. Next, we induced aggregation of SQS particles, and found that QE increased as particles aggregated in DI water because of reduced light scattering and reabsorption, whereas it remained almost constant in the refractive index-matched solvent. Finally, we studied aggregation of highly concentrated silica particle suspensions containing a low concentration of SQS particles, and found that QE increased with aggregation because light scattering and reabsorption were reduced. PMID- 27658533 TI - Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of omega-3-polyunsaturated fatty acids. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) damage the gastrointestinal (GI) epithelial cell membranes by inducing several signals through lipid raft organization after membrane incorporation, whereas omega-3 polyunsaturated fatty acids (PUFAs) relieve inflammation, reduce oxidative stress, and provide cytoprotection, consequent to lipid raft disorganization. Therefore, we hypothesized that omega-3 PUFAs can protect the GI from NSAID-induced damages by initiating the gatekeeper action of cell membranes, subsequent to anti inflammatory and anti-oxidative actions. Administration of indomethacin (IND) leads to the formation of lipid rafts and activation of caveolin-1; however, no such observations were made upon co-administration of eicosapentaenoic acid (EPA) and IND. In addition, the EPA-induced lipid raft disorganization, caveolin-1 inactivation, and cellular cytotoxicity were inhibited when target cells were knocked-out using G-protein coupled receptor 120 (GPR 120). EPA significantly attenuated IND-induced oxidative damage and apoptosis. IND administration induced significant ulceration, bleeding, and oedema in the stomach or small intestine of wild-type (WT) mice; however, such severe damages to the GI significantly decreased in fat-1 transgenic (TG) mice (P < 0.001), which exhibited decreased cyclooxygenase-2 expression and apoptosis, decreased interleukin-1beta and FAS concentrations, and increased heme oxygenase-1 concentration. Our study indicates that the gatekeeper function of omega-3 PUFAs improves GI safety when administered with NSAID. PMID- 27658530 TI - Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. AB - Altered cell metabolism is a characteristic feature of many cancers. Aside from well-described changes in nutrient consumption and waste excretion, altered cancer cell metabolism also results in changes to intracellular metabolite concentrations. Increased levels of metabolites that result directly from genetic mutations and cancer-associated modifications in protein expression can promote cancer initiation and progression. Changes in the levels of specific metabolites, such as 2-hydroxyglutarate, fumarate, succinate, aspartate and reactive oxygen species, can result in altered cell signalling, enzyme activity and/or metabolic flux. In this Review, we discuss the mechanisms that lead to changes in metabolite concentrations in cancer cells, the consequences of these changes for the cells and how they might be exploited to improve cancer therapy. PMID- 27658536 TI - Phase I/II study of low-dose azacytidine in patients with chronic myeloid leukemia who have minimal residual disease while receiving therapy with tyrosine kinase inhibitors. PMID- 27658535 TI - Economic Evidence for US Asthma Self-Management Education and Home-Based Interventions. AB - The health and economic burden of asthma in the United States is substantial. Asthma self-management education (AS-ME) and home-based interventions for asthma can improve asthma control and prevent asthma exacerbations, and interest in health care-public health collaboration regarding asthma is increasing. However, outpatient AS-ME and home-based asthma intervention programs are not widely available; economic sustainability is a common concern. Thus, we conducted a narrative review of existing literature regarding economic outcomes of outpatient AS-ME and home-based intervention programs for asthma in the United States. We identified 9 outpatient AS-ME programs and 17 home-based intervention programs with return on investment (ROI) data. Most programs were associated with a positive ROI; a few programs observed positive ROIs only among selected populations (eg, higher health care utilization). Interpretation of existing data is limited by heterogeneous ROI calculations. Nevertheless, the literature suggests promise for sustainable opportunities to expand access to outpatient AS ME and home-based asthma intervention programs in the United States. More definitive knowledge about how to maximize program benefit and sustainability could be gained through more controlled studies of specific populations and increased uniformity in economic assessments. PMID- 27658537 TI - Direct nematicidal effects of methyl jasmonate and acibenzolar-S-methyl against Meloidogyne incognita. AB - The aim of this study was to examine the nematicidal properties of two defence inducers against the root-knot nematode Meloidogyne incognita. A direct-contact bioassay was applied to evaluate the nematicidal effects of acibenzolar-S-methyl (ASM) and methyl jasmonate (MEJA) on second-stage juveniles (J2). Nematodes were incubated in different concentrations of these compounds, and the numbers of immobile nematodes were counted after 24 and 48 h post incubation. Tap water was then added to verify whether the nematodes recovered or remained dead at 72 h. The percentage of dead nematodes was used as indicator for the toxicity of the different solutions. Our results show that ASM, in the formulation of Bion(r), and MEJA have nematicidal properties. PMID- 27658538 TI - Obsessive-compulsive skin disorders: a novel classification based on degree of insight. AB - Individuals with obsessive-compulsive features frequently visit dermatologists for complaints of the skin, hair or nails, and often progress towards a chronic relapsing course due to the challenge associated with accurate diagnosis and management of their psychiatric symptoms. The current DSM-5 formally recognizes body dysmorphic disorder, trichotillomania, neurotic excoriation and body focused repetitive behavior disorder as psychodermatological disorders belonging to the category of Obsessive-Compulsive and Related Disorders. However there is evidence that other relevant skin diseases such as delusions of parasitosis, dermatitis artefacta, contamination dermatitis, AIDS phobia, trichotemnomania and even lichen simplex chronicus possess prominent obsessive-compulsive characteristics that do not necessarily fit the full diagnostic criteria of the DSM-5. Therefore, to increase dermatologists' awareness of this unique group of skin disorders with OCD features, we propose a novel classification system called Obsessive Compulsive Insight Continuum. Under this new classification system, obsessive compulsive skin manifestations are categorized along a continuum based on degree of insight, from minimal insight with delusional obsessions to good insight with minimal obsessions. Understanding the level of insight is thus an important first step for clinicians who routinely interact with these patients. PMID- 27658539 TI - The genetics of nonsyndromic bilateral Duane retraction syndrome. AB - PURPOSE: To assess the importance of monogenic mutations and chromosomal copy number variants (CNVs) in the occurrence of nonsyndromic bilateral Duane retraction syndrome (bilateral nsDRS). METHODS: The medical records of 12 patients with bilateral nsDRS were reviewed. Genes associated with DRS and associated congenital cranial dysinnervation disorders (SALL4, CHN1, HOXA1, TUBB3, and KIF21A) were sequenced in the standard fashion in each patient. Array comparative genomic hybridization (array CGH) was performed using Affymetrix Cytogenetics Whole-Genome 2.7M array, and the results were analyzed using Affymetrix Chromosome Analysis Suite v1.2. CNVs were assessed as unlikely to be pathologic if they were also present in the Database of Genomic Variants (DGV) or our local database of array CGH results in 150 normal individuals of Middle Eastern ethnicity. RESULTS: No patient had a sequence mutation in SALL4, CHN1, HOXA1, TUBB3, or KIF21A. These 12 patients each had 36-42 chromosomal deletions and/or duplications (mean with standard deviation, 26.25 +/- 6.77), but all of these CNVs were present either in the DGV or in our local database of normal individuals of similar ethnicity and, therefore, are considered nonpathogenic. CONCLUSIONS: The results reported here suggest that bilateral nsDRS is not usually associated with mutations in these genes or with chromosomal CNVs. Current evidence suggests other factors such as epigenetic and/or teratogenic abnormalities may be a potential cause of bilateral nsDRS. PMID- 27658540 TI - Anterior nasal transposition of the inferior oblique muscle can cause antielevation syndrome. AB - We present a case of acquired severe excyclotropia that occurred following multiple orbital wall fracture and traumatic superior oblique palsy in an 18-year old man. The patient suffered from severe torsional diplopia in the right eye; double Maddox rod testing showed excylotorsion of 25 degrees . After anterior nasal transposition of the right inferior oblique muscle, His subjective torsional diplopia improved; however, severe antielevation syndrome was noted after surgery. PMID- 27658541 TI - Non-carious cervical lesions (NCCLs) in a random sampling community population and the association of NCCLs with occlusive wear. AB - This study investigated the prevalence, risk factors and association of occlusive wear with non-carious cervical lesions (NCCLs) in the general Chinese population. A total of 1320 subjects were recruited, and multistage and random sampling methods of survey spots were performed. All age groups comprised similar numbers of participants and equal numbers of males and females. Each subject completed a structured interview, and all teeth of each subject were examined by a practitioner to determine NCCLs and occlusive wear. Binary logistic regression was conducted by analysing the association of risk factors with the occurrence of NCCLs. Bivariate correlation analysis was performed by determining the association of NCCLs dimension or depth with the range of occlusive wear facets. Clinical assessment showed that the overall prevalence of subjects diagnosed with NCCLs was 63%. The proportion of subjects or teeth with NCCLs significantly increased with age. Pre-molars were the most commonly affected teeth. Single variables and interactive effects of variables associated with the occurrence of NCCLs include the following: age group, intensity of toothbrushing, frequency of fresh fruit consumption and interactive effect between intensity of toothbrushing and frequency of fresh fruit consumption. A weak positive correlation of the grading index was found between NCCLs dimension, size or depth and range of occlusive wear facets. This study reported the higher prevalence of NCCLs in the general Chinese population. Implementation of a combined strategy to reduce risk factors of NCCLs could be more effective than individual techniques; meanwhile, the occurrence of NCCL could be related to the wear degree of occlusive defects in the population studied. PMID- 27658542 TI - Body mass and cognitive decline are indirectly associated via inflammation among aging adults. AB - Inflammatory models of neurodegeneration suggest that higher circulating levels of inflammation can lead to cognitive decline. Despite established independent associations between greater body mass, increased inflammation, and cognitive decline, no prior research has explored whether markers of systemic inflammation might mediate the association between body mass and changes in cognitive functioning. To test such a model, we used two longitudinal subsamples (ns=9066; 12,561) of aging adults from the English Longitudinal Study of Ageing (ELSA) study, which included two cognitive measures components of memory and executive functioning, as well as measurements of body mass and systemic inflammation, assessed via C-reactive protein (CRP). Greater body mass was indirectly associated with declines in memory and executive functioning over 6years via relatively higher levels of CRP. Our results suggest that systemic inflammation is one biologically plausible mechanism through which differences in body mass might influence changes in cognitive functioning among aging adults. PMID- 27658543 TI - Platelet CD40L induces activation of astrocytes and microglia in hypertension. AB - Studies have demonstrated separately that hypertension is associated with platelet activation in the periphery (resulting in accumulation and localized inflammatory response) and glial activation in the brain. We investigated the contribution of platelets in brain inflammation, particularly glial activation in vitro and in a rat model of hypertension. We found that HTN increased the expression of adhesion molecules like JAM-1, ICAM-1, and VCAM-1 on brain endothelium and resulted in the deposition of platelets in the brain. Platelet deposition in hypertensive rats was associated with augmented CD40 and CD40L and activation of astrocytes (GFAP expression) and microglia (Iba-1 expression) in the brain. Platelets isolated from hypertensive rats had significantly higher sCD40L levels and induced more prominent glial activation than platelets from normotensive rats. Activation of platelets with ADP induced sCD40L release and activation of astrocytes and microglia. Moreover, CD40L induced glial (astrocytes and microglia) activation, NFkB and MAPK inflammatory signaling, culminating in neuroinflammation and neuronal injury (increased apoptotic cells). Importantly, injection of ADP-activated platelets into normotensive rats strongly induced activation of astrocytes and microglia and increased plasma sCD40L levels compared with control platelets. On the contrary, inhibition of platelet activation by Clopidogrel or disruption of CD40 signaling prevented astrocyte and microglial activation and provided neuroprotection in both in vivo and in vitro conditions. Thus, we have identified platelet CD40L as a key inflammatory molecule for the induction of astrocyte and microglia activation, the major contributors to inflammation-mediated injury in the brain. PMID- 27658545 TI - [Clinical and pathological features of breast cancer in a population of Mexico]. AB - BACKGROUND: Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in Mexico are described. MATERIAL AND METHODS: A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. RESULTS: A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. CONCLUSION: In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions. PMID- 27658544 TI - Activated GL7+ B cells are maintained within the inflamed CNS in the absence of follicle formation during viral encephalomyelitis. AB - Central nervous system (CNS) inflammation associated with viral infection and autoimmune disease results in the accumulation of B cells in various differentiation stages. However, the contribution between peripheral and CNS activation remains unclear. During gliatropic coronavirus induced encephalomyelitis, accumulation of protective antibody secreting cells is preceded by infiltration of B cells with a naive and early differentiation phenotype (Phares et al., 2014). Investigation of the temporal dynamics of B cell activation in draining cervical lymph nodes (CLN) and the CNS revealed that peak CNS infiltration of early activated, unswitched IgD+ and IgM+ B cells coincided with polyclonal activation in CLN. By contrast, isotype-switched IgG+ B cells did not accumulate until peripheral germinal center formation. In the CNS, unswitched B cells were confined to the perivascular space and meninges, with only rare B cell clusters, while isotype-switched B cells localized to parenchymal areas. Although ectopic follicle formation was not observed, more differentiated B cell subsets within the CNS expressed the germinal center marker GL7, albeit at lower levels than CLN counterparts. During chronic infection, CNS IgDint and IgD- B cell subsets further displayed sustained markers of proliferation and CD4 T cell help, which were only transiently expressed in the CLN. A contribution of local CD4 T cell help to sustain B cell activation was supported by occasional B cells adjacent to T cells. The results suggest that accumulation of differentiated B cell subsets within the CNS is largely dictated by peripheral activation, but that local events contribute to their sustained activation independent of ectopic follicle formation. PMID- 27658546 TI - Flavonoid compounds from the red marine alga Alsidium corallinum protect against potassium bromate-induced nephrotoxicity in adult mice. AB - Potassium bromate (KBrO3 ), an environmental pollutant, is a well-known human carcinogen and a potent nephrotoxic agent. Currently, natural products have built a well-recognized role in the management of many diseases induced by pollutants. As potent natural sources of bioactive compounds, marine algae have been demonstrated to be rich in novel secondary metabolites with a broad range of biological functions. In this study, adults male mice were orally treated for 15 days with KBrO3 (0.5 g/L) associated or not with extract of Alsidium corallinum, a red Mediterranean alga. In vitro study demonstrated that algal extract has antioxidant efficacy attributable to the presence of flavonoids and polyphenols. Among these, Liquid chromatography-mass spectrometry analysis showed A. corallinum is rich in kaempferol, apigenin, catechin, and quercetin flavonoids. In vivo study showed that supplementation with the alga significantly prevented KBrO3 -induced nephrotoxicity as indicated by plasma biomarkers (urea, uric acid, and creatinin levels) and oxidative stress related parameters (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C, hydrogen peroxide, protein oxidation products) in kidney tissue. The corrective effect of A. corallinum on KBrO3 -induced kidney injury was also supported by molecular and histopathological observations. In conclusion, it was established that the red alga, thanks to its bioactive compounds, effectively counteracts toxic effects of KBrO3 and could be a useful coadjuvant agent for treatment of this pollutant poisonings. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1475-1486, 2017. PMID- 27658548 TI - PTPN2-deficiency exacerbates T follicular helper cell and B cell responses and promotes the development of autoimmunity. AB - Non-coding single nucleotide polymorphisms that repress PTPN2 expression have been linked with the development of type 1 diabetes, rheumatoid arthritis and Crohn's disease. PTPN2 attenuates CD8+ T cell responses to self and prevents overt autoreactivity in the context of T cell homeostasis and antigen cross presentation. The role of PTPN2 in other immune subsets in the development of autoimmunity remains unclear. Here we show that the inducible deletion of PTPN2 in hematopoietic compartment of adult non-autoimmune prone mice results in systemic inflammation and autoimmunity. PTPN2-deficient mice had increased inflammatory monocytes, B cells and effector T cells in lymphoid and non-lymphoid tissues and exhibited symptoms of dermatitis, glomerulonephritis, pancreatitis and overt liver disease. Autoimmunity was characterised by the formation of germinal centers in the spleen and associated with markedly increased germinal center B cells and T follicular helper (Tfh) cells and circulating anti-nuclear antibodies, inflammatory cytokines and immunoglobulins. CD8+ T cell proliferative responses were enhanced, and interleukin-21-induced STAT-3 signalling in Tfh cells and B cells was increased and accompanied by enhanced B cell proliferation ex vivo. These results indicate that deficiencies in PTPN2 across multiple immune lineages, including naive T cells, Tfh cells and B cells, contribute to the development of autoimmunity. PMID- 27658549 TI - An Unusual Cause of Persistent Crying in a Toddler. AB - BACKGROUND: Excessive or persistent crying is a common presentation to the pediatric emergency department, and often poses a diagnostic dilemma to emergency physicians. There are several reasons for excessive or persistent crying in children, ranging from benign causes like hunger, to life-threatening causes such as intussusception. CASE REPORT: We report an interesting case of a toddler whose cause of excess crying, with no detectable clinical clues, was eventually attributed to a foreign body in the esophagus. A brief review of diagnostic approach to excess crying and management of ingested foreign bodies is presented. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ingested foreign body is a potential cause of persistent crying, and early recognition can result in definitive treatment and prevention of potential mortality and morbidity. PMID- 27658547 TI - Cadmium-induced heme-oxygenase-1 expression plays dual roles in autophagy and apoptosis and is regulated by both PKC-delta and PKB/Akt activation in NRK52E kidney cells. AB - Heme oxygenase-1 (HO-1) protects cells against cadmium (Cd)-induced oxidative stress. However, the mechanism underlying this protection is not well understood. In this study, we elucidated the role of HO-1 in Cd-induced cytotoxicity. Exposure of NRK52E cells to Cd induced protein kinase B (PKB)/Akt, protein kinase C (PKC)-delta, and glycogen synthase kinase (GSK) 3alphab phosphorylation, and eukaryotic initiation factor (eIF) 2alpha dephosphorylation. Pharmacological inhibition of Akt resulted in HO-1 suppression and eIF2alpha activation, which partially suppressed CHOP and PARP-1 cleavage, but promoted autophagy and decreased cell viability. Pharmacological inactivation of PKC-delta markedly suppressed Cd-induced phospho-serine (p-Ser) GSK3alphabeta, and HO-1, and partially inhibited PARP-1 cleavage, but massively induced autophagy and decreased cell viability. Pharmacological upregulation of p-Ser GSK3alphabeta enhanced Cd-induced HO-1, CHOP, and PARP-1 cleavage, but decreased autophagy. Genetic deficiency of GSK3beta suppressed HO-1 and PARP-1 cleavage and increased autophagy. Genetic suppression of HO-1 reduced Cd-induced PARP-1 cleavage, but increased LC3-II. Cd exposure led to accumulation of p-PKC-delta, p-Ser GSK3alphabeta, and HO-1 in the nucleus and particulate fractions, suggesting that they have dual functions in response to Cd. N-acetylcysteine treatment suppressed Cd-induced activation of PKC-delta and Akt. These results indicate that HO-1 induced by Cd exposure is regulated by PKC-delta, p-Ser GSK3alphabeta, and PKB/Akt, which restrain autophagic cell death, but mildly induce apoptosis in NRK52E cells. Together, the results suggest that HO-1 expression in response to Cd maintains cellular homeostasis during oxidative stress. PMID- 27658550 TI - Calcaneus Fractures: A Possible Musculoskeletal Emergency. AB - BACKGROUND: Calcaneal fractures are commonly seen and treated in the emergency department. There are subsets of calcaneal fractures that pose a high risk to the adjacent soft tissue of the heel and can result in full-thickness tissue necrosis. OBJECTIVE: To identify which calcaneal fractures need to be managed within hours and triaged to the orthopedic team and which can be temporized in a neutral or plantarflexed ankle splint and seen in an outpatient setting. DISCUSSION: Tongue-type calcaneal fractures and tuberosity fractures must be triaged appropriately within the first few hours of presentation to prevent skin compromise. This requires the emergency physician to understand the radiographic morphology of the fracture as well as the clinical signs of skin compromise. Communication with the orthopedic surgery service is essential and splinting in a specific manner is important to stabilize the soft tissue envelope. CONCLUSION: Recognizing the calcaneal injury pattern and implementing the correct treatment strategy is paramount to having successful patient outcomes. A delay or error in treatment can turn a closed fracture into an open fracture. PMID- 27658551 TI - Acute Promyelocytic Leukemia Presenting as Focal Neurologic Findings and Deteriorating Mental Status. AB - BACKGROUND: Acute promyelocytic leukemia (APL) is a rare but particularly malignant form of acute leukemia that is characterized by a rapid progression to fatal hemorrhage. Survival rates of patients with APL have increased with the introduction of all-trans retinoic acid (ATRA), but early deaths caused by hemorrhage still persist. CASE REPORT: A man with undiagnosed APL presenting with focal neurologic findings and deteriorating altered mental status caused by an intracranial hemorrhage is discussed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to consider APL when diagnosing etiologies for intracranial hemorrhage. In addition to standard care, early administration of ATRA is recommended upon clinical suspicion of the disease. PMID- 27658552 TI - Appendicitis Presenting As Cellulitis of the Right Leg. AB - BACKGROUND: Several infectious processes of intra-abdominal origin may atypically present as skin or soft tissue infections or abscess in the thigh. CASE REPORT: We describe the case of a 73-year-old woman who presented to the emergency department with the clinical picture of a skin infection of the right leg. The patient's condition deteriorated during medical treatment with intravenous antibiotics. Subsequent radiologic imaging revealed that the complaints were caused by a bulging retroperitoneal appendicular abscess along the iliopsoas muscle, although the patient experienced no abdominal symptoms. The patient recovered completely after surgical intervention. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Timely performance of anatomic imaging in patients with unexplained skin or soft tissue infections and thigh abscesses is important because these findings may be manifestations of an abdominal pathology. A correct diagnosis in the emergency department prohibits delays in treatment. PMID- 27658553 TI - Sudden Weakness in A Young Healthy Man. PMID- 27658554 TI - Chestnut Sign: Metronidazole-Induced Encephalopathy. PMID- 27658555 TI - A Physician's Moral Dilemma in the Emergency Department: Going Against a Patient's Perceived Wishes. AB - OBJECTIVES: We describe a case where a patient at the end of life with an advanced medical directive in place presents to the ED in distress. CASE REPORT: Our case is of a middle aged male with advanced cancer who presents in the ED with his family in respiratory distress requiring intubation. Even though his advanced medical directive states not for prolonged life sustaining support his wife and daughters plead with the physicians to save his life in order to end his suffering as well as prepare them for a more peaceful death. CONCLUSION: We discuss the ethical and moral distress faced by ED physicians in such acute scenarios where a patient's perceived wishes are not in line with their families' pleas. PMID- 27658556 TI - Comments on Spinal Intramedullary Cysticercosis. PMID- 27658557 TI - Allergic Contact Dermatitis from Topical Acyclovir: Case Series. AB - BACKGROUND: Despite the widespread use of oral or topical acyclovir, allergic contact dermatitis caused by it has been rarely reported, with fewer than 20 case studies published in the English literature to date. CASE REPORTS: A diagnosis of allergic contact dermatitis from acyclovir cream was established in a 62-year-old female patient who had been continuously using acyclovir cream for 3 weeks after systemic therapy for herpes zoster with acyclovir, and in a 35-year-old female patient, who had undergone liver transplantation in 2008 and subsequently developed a severe form of herpes zoster treated orally with 4 g/day acyclovir and prolonged topical administration of acyclovir cream. In both cases, patch tests were performed with extended European Baseline Series, with the excipients of acyclovir cream (propylene glycol, sodium lauryl sulfate, cetostearyl alcohol, dimethyl sulfoxide) and commercial cream containing acyclovir 2%. Positive reactions were obtained only with the commercial cream with acyclovir 2%. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Allergic contact dermatitis caused by acyclovir is rarely reported and frequently misdiagnosed, despite the wide use of oral or topical acyclovir. Allergic contact dermatitis due to acyclovir applied topically is a clinical problem with which health care providers should be familiar, and which prompts patch testing in suspected patients. Knowledge and education focused on allergens are important to clinicians in daily practice. PMID- 27658559 TI - A Novel Esophageal Heat Transfer Device for Temperature Management in an Adult Patient with Severe Meningitis. PMID- 27658558 TI - Safety and Efficacy of the "Easy Internal Jugular (IJ)": An Approach to Difficult Intravenous Access. AB - BACKGROUND: The easy internal jugular (Easy IJ) technique involves placement of a single-lumen catheter in the internal jugular vein using ultrasound guidance. This technique is used in patients who do not have suitable peripheral or external jugular venous access. The efficacy and safety of this procedure are unknown. OBJECTIVE: We aimed to estimate efficacy and safety parameters for the Easy IJ when used in emergency department (ED) settings. METHODS: We conducted a prospective study of the Easy IJ in stable ED patients with severe intravenous access difficulty. The study was conducted simultaneously at two academic EDs and a community university-affiliated ED. Patients were selected for failure of alternative access, hemodynamic stability, and ability to increase the IJ diameter with the Valsalva maneuver. Emergency physicians prepped the skin and inserted an 18-gauge, 4.8-cm catheter using a limited sterile technique. We collected the following data: patient body mass index, age, procedure time, pain score, initial success, loss of patency, occurrence of pneumothorax, infection, or arterial puncture. RESULTS: We recorded 83 attempts in 74 patients, with a median age of 44 years and a median body mass index of 27 kg/m2. The initial success rate was 88%, with a mean procedure time of 4.4 min (95% confidence interval 3.8-4.9). The average pain score was 3.9 out of 10 (95% confidence interval 3.4-4.5). Ten of 73 successful lines (14%) lost patency. There were no cases of pneumothorax, arterial puncture, or line infection. CONCLUSION: The Easy IJ was inserted successfully in 88% of cases, with a mean time of 4.4 min. Loss of patency, the only complication, occurred in 14% of cases. PMID- 27658560 TI - Extended immunologic and genetic lineage of mammary analogue secretory carcinoma of salivary glands. AB - Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. To explore a more practical and convenient immunohistochemical approach to distinguish MASC from other tumors arising from salivary glands as well as to expand the immunologic and genetic lineage of MASC, we examined 17 MASCs using clinicopathologic, immunohistochemical, and molecular analyses. Eighteen cases of acinic cell carcinoma, 18 cases of adenoid cystic carcinoma, 22 cases of mucoepidermoid carcinoma, and 14 cases of basal cell adenocarcinoma were brought in for comparison. Seventeen MASCs shared similar architectures with not only intraluminal or intracellular secretion but also low grade vesicular nuclei. In addition, they were all immunoreactive for S-100 and SOX-10, whereas only 3 of 17 demonstrated reactivity for GATA-3 and P63, and 4 of 17 were focally positive for CD117. ETV6 translocation was detected in 10 cases by fluorescence in situ hybridization, whereas intact ETV6 was noted in 2 cases. Our data proposed a combined immunohistochemical panel to distinguish MASC from other tumors arising from salivary glands and expanded the immunologic and genetic lineage of MASC. PMID- 27658561 TI - Sutures and surgical site infections: children versus adults and single centre versus multicentre trials. PMID- 27658562 TI - Triclosan-containing sutures versus ordinary sutures for reducing surgical site infections in children: a double-blind, randomised controlled trial. AB - BACKGROUND: Surgical site infections (SSIs) are a pervasive problem in surgery. Sutures coated or impregnated with triclosan might reduce the occurrence of SSIs, but evidence of their efficacy is limited, especially in children. METHODS: We designed a randomised, double-blind, controlled trial in patients who underwent elective or daytime emergency surgery at Oulu University Hospital (Oulu, Finland). We included children younger than 18 years staying in the paediatric surgery and orthopaedics ward for any elective or emergency surgery during the daytime and with anticipated use of absorbing sutures. Children were randomly allocated (1:1) to receive either triclosan-containing sutures or ordinary absorbing sutures. The primary outcome was the occurrence of superficial or deep surgical site infections according to the Centers for Disease Control and Prevention criteria within 30 days after surgery. The primary analysis was with modified intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01220700. FINDINGS: Between September, 2010, and December, 2014, 1633 children were recruited. In the modified intention-to-treat group, SSIs occurred in 20 (3%) of 778 patients allocated to receive triclosan-containing sutures and in 42 (5%) of 779 patients allocated to receive control sutures (risk ratio 0.48, 95% CI 0.28-0.80). To prevent one SSI, triclosan-containing sutures had to be used in 36 children (95% CI 21-111). One patient died from suspected mitochondrial disease; no other expected or unexpected adverse events were reported in either of the groups. INTERPRETATION: Use of triclosan-containing sutures effectively reduced the occurrence of all SSIs compared with normal sutures. The results accord with the results of meta-analyses of previous studies in adults. Use of triclosan-containing sutures is a simple way to reduce SSIs in children. FUNDING: The Alma and K A Snellman Foundation. PMID- 27658563 TI - Microfluidic enrichment of circulating tumor cells in patients with clinically localized prostate cancer. AB - BACKGROUND: Circulating tumor cells (CTC) have become an important tool in the monitoring of patients with advanced prostate cancer (PC). The role of CTC in localized disease has been addressed by only few studies. However, results of CTC analyses are strongly dependent on the platform used for CTC enrichment and detection. In the present study, a microfluidic platform allowing for antigen independent enrichment of CTC was investigated for its ability to detect CTC in patients with clinically localized PC. PATIENTS AND METHODS: Blood (2ml) was collected preoperatively from 50 consecutive patients undergoing radical prostatectomy for clinically localized PC. CTC were enriched using a microfluidic ratchet mechanism allowing separation of CTC from white blood cells based on differences in size and deformability. Enriched cells were stained for immunofluorescence with antibodies targeting pancytokeratin, epithelial cell adhesion molecule, and CD45. In 21 patients, we performed staining for the androgen receptor. CTC counts were correlated with clinical and pathological parameters using the Wilcoxon-Mann-Whitney test for continuous parameters and Chi square test for categorical parameters. RESULTS: CTC were detected in 25 (50%) patients. The median number of CTC in CTC-positive patients was 9 CTC/2ml (range: 1-417). Pancytokeratin positive CTC showed expression of androgen the receptor. We observed no correlation between CTC counts and prostate-specific antigen concentration, tumor stage, lymph node stage, or Gleason grade. CONCLUSION: In a representative cohort of patients with clinically localized PC, CTC can be detected in a considerable proportion of patients when using a new microfluidic ratchet mechanism. This encourages further studies assessing the prognostic effect of antigen-independent enriched CTC in patients with PC. PMID- 27658564 TI - Follow-up after surgery for hemorrhagic AMD. AB - INTRODUCTION: The long-term functional results of macular hematoma (MH) surgery in exudative AMD are often limited. The goal of this study was to compare visual outcomes of monthly versus bimestrial follow-up in these patients. METHODS: Retrospective, interventional case series. Population : 21 eyes of 21 patients with SMH associated with exudative AMD. INCLUSION CRITERIA: first SMH associated with exudative AMD, with 1-year postoperative follow-up. EXCLUSION CRITERIA: blood located exclusively underneath the retinal pigment epithelium on OCT imaging, SMH due to different etiology, lost to follow-up, <=5 postoperative visits and a different surgical protocol as described. Patients were divided into two groups according to the number of postoperative visits (number of intravitreal injections [IVT] combined with the number of consultations, only one visit was recorded when IVT and consultation occurred on the same day) during the 1-year postoperative follow-up: group 1 had >=11 visits (n=8); group 2 had 6 to 10 visits (n=13). All eyes underwent vitrectomy with subretinal injection of recombinant tissue plasminogen activator, fluid-gas exchange and anti-VEGF intravitreal injection. The main outcome was change in best-corrected visual acuity (BCVA). RESULTS: Considering visual acuity (VA) change between 1-month and 1-year postoperative follow-up examinations, group 1 had statistically significant greater VA changes (logMAR -0.29+/-0.44 vs logMAR 0.42+/-0.73; P=0.016; P=0.016). In patients that had exudative recurrences (ER), group 1 received more anti-VEGF IVT than group 2 (P=0.045). CONCLUSION: Our results showed that monthly follow-up, between the IVT series, is highly recommended to preserve postoperative VA in patients undergoing surgery for SMH associated with AMD. PMID- 27658565 TI - [Purtscher retinopathy: Role of optical coherence tomography (OCT) in diagnosis, monitoring and prognostic evaluation]. PMID- 27658566 TI - Resting cardiac vagal tone predicts intraindividual reaction time variability during an attention task in a sample of young and healthy adults. AB - Intraindividual reaction time variability (IIV), defined as the variability in trial-to-trial response times, is thought to serve as an index of central nervous system function. As such, greater IIV reflects both poorer executive brain function and cognitive control, in addition to lapses in attention. Resting-state vagally mediated heart rate variability (vmHRV), a psychophysiological index of self-regulatory abilities, has been linked with executive brain function and cognitive control such that those with greater resting-state vmHRV often perform better on cognitive tasks. However, research has yet to investigate the direct relationship between resting vmHRV and task IIV. The present study sought to examine this relationship in a sample of 104 young and healthy participants who first completed a 5-min resting-baseline period during which resting-state vmHRV was assessed. Participants then completed an attentional (target detection) task, where reaction time, accuracy, and trial-to-trial IIV were obtained. Results showed resting vmHRV to be significantly related to IIV, such that lower resting vmHRV predicted higher IIV on the task, even when controlling for several covariates (including mean reaction time and accuracy). Overall, our results provide further evidence for the link between resting vmHRV and cognitive control, and extend these notions to the domain of lapses in attention, as indexed by IIV. Implications and recommendations for future research on resting vmHRV and cognition are discussed. PMID- 27658567 TI - Cytoprotective effect of autophagy on phagocytosis of apoptotic cells by macrophages. AB - Clearance of the apoptotic cells by phagocytes plays pivotal roles in maintenance of tissue homeostasis, promotion of immunological tolerance and anti-inflammatory response. Recent studies show that autophagy is involved in phagocytosis of the apoptotic cells. However, contribution of autophagy to phagocytosis of the apoptotic cells by macrophages is not clearly defined. Here, we assessed cytoprotective effect of autophagy on clearance of the apoptotic cells. Apoptosis of murine splenic lymphocytes and human T-cell leukemia cells was induced with cyclophosphamide. After engulfment of the apoptotic cells, expression of Belin-1 and LC3 in macrophages was upregulated, the number of MDC-positive vesicles, LC3 positive autophagosomes and autophagic ultrastructures increased significantly. Autophagosome was fused with phagosome containing fragments of the nuclei or other debris of the apoptotic cells to form amphisome. Some cells in macrophages phagocytosing the apoptotic cells became apoptotic. After autophagy of macrophages was inhibited with 3-MA, viability and survival of macrophages reduced, phagocytosis of the apoptotic cells by macrophages deceased significantly. These results demonstrate that autophagy plays an important role in promoting clearance of the apoptotic cells by protecting macrophages from apoptosis during phagocytosis as well as degrading the contents of phagosomes via amphisome formation. PMID- 27658569 TI - Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions. AB - Mesenchymal stem cells (MSCs), which were first isolated from the bone marrow, are now being extracted from various other tissues in the body, including the adipose tissue. The current study presents systematic evidence of how the adipose tissue-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (Bm-MSCs) behave when cultured in specific pro-adipogenic microenvironments. The cells were first characterized and identified as MSCs in terms of their morphology, phenotypic expression, self-renewal capabilities and multi-lineage potential. Subsequently, the proliferation and gene expression profiles of the cell populations cultured on two-dimensional (2D) adipose tissue extracellular matrix (ECM)-coated tissue culture plastic (TCP) and in three-dimensional (3D) AlgiMatrix(r) microenvironments were analyzed. Overall, it was found that adipogenesis was triggered in both cell populations due to the presence of adipose tissue ECM. However, in 3D microenvironments, ASCs and Bm-MSCs were predisposed to the adipogenic and osteogenic lineages respectively. Overall, findings from this study will contribute to ongoing efforts in adipose tissue engineering as well as provide new insights into the role of the ECM and cues provided by the immediate microenvironment for stem cell differentiation. PMID- 27658568 TI - Overexpression of microRNA-1288 in oesophageal squamous cell carcinoma. AB - PURPOSE: This study aims to examine the expression profiles miR-1288 in oesophageal squamous cell carcinoma (ESCC). The cellular implications and target interactions of ESCC cells following miR-1288 overexpression was also examined. METHODS: In total, 120 oesophageal tissues (90 primary ESCCs and 30 non neoplastic tissues) were recruited for miR-1288 expression analysis using qRT PCR. An exogenous miR-1288 mimic and its inhibitor were used to explore the in vitro effects of miR-1288 on ESCC cells by performing cell proliferation, colony formation, cell invasion and migration assays. Localisation and modulatory changes of various miR-1288 regulated proteins such as FOXO1, p53, TAB3, BCL2 and kRAS was examined using immunofluorescence and western blot. RESULTS: Overexpression of miR-1288 was more often noted in ESCC tissues when compared to non-neoplastic oesophageal tissues. High expression was often noted in high grade carcinomas and with metastases. Patients with high levels of miR-1288 expression showed a slightly better survival compared to patients with low miR-1288 levels. Furthermore, overexpression of miR-1288 showed increased cell proliferation and colony formation, improved cell migration and enhanced cell invasion properties in ESCC cells. In addition, miR-1288 overexpression in ESCC cells showed repression of cytoplasmic tumour suppressor FOXO1 protein expression. Inversely, inhibition of miR-1288 expression exhibited remarkable upregulation of FOXO1 protein, while expressions of other tested proteins remain unchanged. CONCLUSIONS: Up regulation of miR-1288 expression in ESCC tissues and miR-1288 induced oncogenic features of ESCC cells in-vitro indicates the oncogenic roles of miR-1288 in ESCCs. Overexpression of miR-1288 play a key role in the pathogenesis of ESCCs and its modulation may have potential therapeutic value in patients with ESCC. PMID- 27658570 TI - Distinct hydrophobic "patches" in the N- and C-tails of beta-catenin contribute to nuclear transport. AB - beta-catenin is a key mediator of Wnt signaling and its deregulated nuclear accumulation can drive cancer progression. While the central armadillo (Arm) repeats of beta-catenin stimulate nuclear entry, the N- and C-terminal "tail" sequences are thought to regulate turnover and transactivation. We show here that the N- and C-tails are also potent transport sequences. The unstructured tails of beta-catenin, when individually fused to a GFP-reporter, could enter and exit the nucleus rapidly in live cells. Proximity ligation assays and pull-down assays identified a weak interaction between the tail sequences and the FG-repeats of nucleoporins, consistent with a possible direct translocation of beta-catenin through the nuclear pore complex. Extensive alanine mutagenesis of the tail sequences revealed that nuclear translocation of beta-catenin was dependent on specific uniformly distributed patches of hydrophobic residues, whereas the mutagenesis of acidic amino acids had no effect. Moreover, the mutation of hydrophobic patches within the N-tail and C-tail of full length beta-catenin reduced nuclear transport rate and diminished its ability to activate transcription. We propose that the tail sequences can contribute to beta-catenin transport and suggest a possible similar role for hydrophobic unstructured regions in other proteins. PMID- 27658571 TI - Characterizing the (Perceived) Newsworthiness of Health Science Articles: A Data Driven Approach. AB - BACKGROUND: Health science findings are primarily disseminated through manuscript publications. Information subsidies are used to communicate newsworthy findings to journalists in an effort to earn mass media coverage and further disseminate health science research to mass audiences. Journal editors and news journalists then select which news stories receive coverage and thus public attention. OBJECTIVE: This study aims to identify attributes of published health science articles that correlate with (1) journal editor issuance of press releases and (2) mainstream media coverage. METHODS: We constructed four novel datasets to identify factors that correlate with press release issuance and media coverage. These corpora include thousands of published articles, subsets of which received press release or mainstream media coverage. We used statistical machine learning methods to identify correlations between words in the science abstracts and press release issuance and media coverage. Further, we used a topic modeling-based machine learning approach to uncover latent topics predictive of the perceived newsworthiness of science articles. RESULTS: Both press release issuance for, and media coverage of, health science articles are predictable from corresponding journal article content. For the former task, we achieved average areas under the curve (AUCs) of 0.666 (SD 0.019) and 0.882 (SD 0.018) on two separate datasets, comprising 3024 and 10,760 articles, respectively. For the latter task, models realized mean AUCs of 0.591 (SD 0.044) and 0.783 (SD 0.022) on two datasets-in this case containing 422 and 28,910 pairs, respectively. We reported most predictive words and topics for press release or news coverage. CONCLUSIONS: We have presented a novel data-driven characterization of content that renders health science "newsworthy." The analysis provides new insights into the news coverage selection process. For example, it appears epidemiological papers concerning common behaviors (eg, alcohol consumption) tend to receive media attention. PMID- 27658572 TI - Retraction notice to "A new femoral nail with single distal locking screw for maximum interfragment rotational stability" Acta Orthop Traumatol Turc 2016;50(1):89-96. PMID- 27658573 TI - Risk factors for fatigue in patients with epilepsy. AB - Fatigue is highly prevalent in patients with epilepsy and has a major impact on quality of life, but little data is available on its effects and management in epilepsy. To identify the incidence and risk factors of fatigue in patients with epilepsy, 105 epilepsy patients (45 women and 60 men) were enrolled in our study. Demographic and clinical data were collected and psychological variables including fatigue, sleep quality, excess daytime sleepiness, anxiety, and depression were measured by Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale, respectively. Of 105 patients, 29.5% exhibited fatigue (FSS score ?4). We found no correlation between the occurrence of fatigue and any of our demographic or clinical variables. Fatigue is correlated with low sleep quality, anxiety, and depression, but not with excess daytime sleepiness. Thus, we concluded that fatigue is highly prevalent in patients with epilepsy, and that low sleep quality, anxiety, and depression are significantly correlated with fatigue in epileptics, while excess daytime sleepiness not. PMID- 27658574 TI - Balloon-in-stent assisted coiling for treatment of intracranial overwide and undertall aneurysms. AB - This study reports our experience of balloon-in-stent assisted coiling for the treatment of morphologically unfavorable aneurysms located in the internal carotid artery (ICA). From July 2007 to April 2014, twelve patients with twelve aneurysms located in the ICA were coil embolized by simultaneously using balloon and stent assistance. Five aneurysms were ruptured and seven were unruptured. All the aneurysms were overwide (dome-to-neck ratio ?1.2) and undertall (aspect ratio ?1.2) anatomically. The procedure-related adverse events, clinical and angiographic results were retrospectively analyzed. Intraprocedural aneurysmal bleeding occurred for one unruptured aneurysm but was stopped immediately after the balloon was inflated. Periprocedural thromboembolism occurred for two ruptured aneurysms, leading to death in one patient and severe neurological deficit for the other one. Procedure-related permanent morbidity and mortality rates were 8.3% (1/12) and 8.3% (1/12). Satisfactory (total and subtotal) occlusion was obtained immediately in 11 (91.7%) cases. Nine aneurysms received digital subtraction angiography follow-up (mean 25.1months, range 6-55), and all of them except one were totally obliterated. No aneurysmal bleeding occurred during a mean period of 59.1months, clinical follow-up for eleven patients. Balloon-in-stent assisted coiling might be a therapeutic alternative to prevent growth or rupture of overwide and undertall aneurysms. Nevertheless, it should be used prudently for ruptured ICA aneurysms, for its disadvantage of technical complexity and relatively high rate of adverse events. PMID- 27658575 TI - Differential DNA methylation of the meiosis-specific gene FKBP6 in testes of yak and cattle-yak hybrids. AB - FK506-binding protein 6 (FKBP6) is essential for meiosis during mammalian spermatogenesis. However, the molecular regulation of FKBP6 during spermatogenesis remains unclear. In the present study, we performed molecular characterization of the meiosis-specific gene FKBP6 in yak testes. Yak FKBP6 encodes a polypeptide of 295 amino acid residues with an FK506-binding domain (FKBP_C) and three tetratricopeptide repeat domains. The methylation level of the FKBP6 promoter in testes was significantly higher in cattle-yak with male sterility than in yak, and the FKBP6 promoter was methylated in liver tissues in which FKBP6 is not expressed. FKBP6 promoter activity was significantly decreased after treatment with the M.SssI methyltransferase in vitro. Furthermore, the FKBP6 gene was remarkably activated in bovine mammary epithelial cells treated with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine. Taken together, our results demonstrate for the first time that the FKBP6 promoter is differentially methylated in testes; together with the functional promoter analysis, this suggests that methylation of this promoter may contribute to cattle-yak male infertility. PMID- 27658576 TI - Autosomal dominant auditory neuropathy and variant DIAPH3 (c.-173C>T). PMID- 27658577 TI - Syringocystadenoma papilliferum of the external auditory canal. Case report and literature review. PMID- 27658578 TI - Laryngeal Chondritis in Sheep in Iceland. AB - Laryngeal chondritis is a chronic disease in sheep with low morbidity, high mortality and unresolved pathogenesis. The disease has been recognized recently in Iceland and affects both ewes and rams. Animals of different ages are affected, but lambs and yearlings predominate. The disease is seen in housed animals and most cases occur during the late winter months. We report the gross and microscopical findings in 45 cases of laryngeal chondritis in Icelandic sheep. PMID- 27658579 TI - Totally implantable venous access port via the femoral vein in a femoral port position with CT-venography. AB - BACKGROUND AND PURPOSE: We aimed to determine the success rate and any complications using a percutaneous approach to the femoral vein (FV) for placement of a totally implantable access port (TIVAP), with a preoperative assessment of the femoral and iliac veins using computed tomography-venography (CT-V). METHODS: A prospective study of 72 patients was conducted where placement of a TIVAP was attempted via the right FV, with the port placed in the anterior thigh, when subclavian vein or jugular vein access was contraindicated. Preoperative assessment of the femoral venous plexus was performed with CT-V in 72 patients. RESULTS: CT-V success was achieved in 72 of 72 patients (100%). The average distance between the inguinal ligament and the saphenofeomral (FV-GSV) junction was 42.8 +/- 12.9 mm. The FV approach had a 97% successful cannulation rate. Two patients had a thrombosis in either the femoral vein or the great saphenous vein. One procedural complication (1.4%) and one initial complication (1.4%) occurred. Late complications occurred in four patients (5.7%). CONCLUSIONS: The percutaneous FV approach with CT-V guidance is an option for patients with multiple central venous cannulations, as well as those with bilateral breast cancer, or those undergoing hemodialysis. J. Surg. Oncol. 2016;114:1024-1028. (c) 2016 Wiley Periodicals, Inc. PMID- 27658581 TI - Postoperative analgesic effect, of preoperatively administered dexamethasone, after operative fixation of fractured neck of femur: randomised, double blinded controlled study. AB - BACKGROUND: Fractured neck of femur is a common cause of hospital admission in the elderly and usually requires operative fixation. In a variety of clinical settings, preoperative glucocorticoid administration has improved analgesia and decreased opioid consumption. Our objective was to define the postoperative analgesic efficacy of single dose of dexamethasone administered preoperatively in patients undergoing operative fixation of fractured neck of femur. METHODS: Institutional ethical approval was granted and written informed consent was obtained from each patient. Patients awaiting for surgery at Cork University Hospital were recruited between July 2009 and August 2012. Participating patients, scheduled for surgery were randomly allocated to one of two groups (Dexamethasone or Placebo). Patients in the dexamethasone group received a single dose of intravenous dexamethasone 0.1 mg kg -1 immediately preoperatively. Patients in the placebo group received the same volume of normal saline. Patients underwent operative fixation of fractured neck of femur using standardised spinal anaesthesia and surgical techniques. The primary outcome was pain scores at rest 6 h after the surgery. RESULTS: Thirty seven patients were recruited and data from thirty patients were analysed. The groups were similar in terms of patient characteristics. Pain scores at rest 6 h after the surgery (the principal outcome) were lesser in the dexamethasone group compared with the placebo group [0.8(1.3) vs. 3.9(2.9), mean(SD) p = 0.0004]. Cumulative morphine consumption 24 h after the surgery was also lesser in the dexamethasone group [7.7(8.3) vs. 15.1(9.4), mean(SD) mg, p = 0.04]. CONCLUSIONS: A single dose of intravenous dexamethasone 0.1 mg kg -1 administered before operative fixation of fractured neck of femur improve significantly the early postoperative analgesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01550146 , date of registration: 07/03/2012. PMID- 27658580 TI - Measurement of physical activity in urban and rural South African adults: a comparison of two self-report methods. AB - BACKGROUND: Due to the large mortality from inactivity-related non-communicable diseases in low- and middle- income countries, accurate assessment of physical activity is important for surveillance, monitoring and understanding of physical (in)activity epidemiology in many of these countries. Research on relative performance of self-report physical activity instruments commonly used for epidemiological research in Africa have rarely been reported. The present study compared estimates of physical activity measured with the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and the Baecke Physical Activity Questionnaire (BPAQ) among urban and rural black South African adults. METHODS: Self-reported physical activity data using the IPAQ-SF and BPAQ were collected from a representative sample of 910 urban and rural black South African adults (age = 59.2 +/- 9.5 years, 69.7 % women) participating in the 2015 wave of the Prospective Urban and Rural Epidemiological (PURE) study in the North West Province of South Africa. Between-method relationships (pearson correlations [r] and intraclass correlation coefficients [ICCs]) and agreements (Bland-Altman mean difference with 95 % limits of agreement and Kappa coefficient [k]) of IPAQ-SF and BPAQ variables were estimated. Sensitivity and specificity of the BPAQ relative to the IPAQ-SF to classify individuals according to the international guidelines for sufficient physical activity were calculated using chi-square statistics. RESULTS: Correlations between IPAQ-SF scores and BPAQ indices were small (r = 0.08-0.18; ICCs = 0.09-0.18) for BPAQ leisure and sport indices, moderate-to-large for work index (r = 0.42-0.59; ICCs = 0.40-0.62) and total physical activity index (r = 0.52-0.60; ICCs = 0.36-0.51). Between methods mean difference for total physical activity was large (1.85 unit), and agreement in physical activity classifications was poor to moderate (k = 0.16-0.44). The sensitivity of the BPAQ to identify sufficiently active people from the IPAQ-SF was very good (98 %), but its specificity to correctly classify insufficiently active people was weak (23 %). CONCLUSION: Notable disparities in physical activity estimates between methods suggest that utilization of IPAQ-SF and BPAQ for surveillance and epidemiology studies in Africa should depend on research questions and population to be studied. Future studies with objective measures are needed to confirm the relative validity between the two instruments. PMID- 27658582 TI - Toxoplasma gondii pseudocyst in a transbronchial biopsy: a case report. AB - BACKGROUND: We herein present a case in which a Toxoplasma cyst was found in a transbronchial biopsy specimen from an immunocompetent patient with negative serology for the parasite. CASE PRESENTATION: An 18-year-old Brazilian man presented with a 1-week history of dyspnea and fever and was diagnosed with right lower lobe pneumonia. He began inpatient treatment with intravenous antibiotics. During treatment, a bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was performed. Anatomopathological examination of the transbronchial biopsy showed a small fragment of lung parenchyma with discrete septal thickening and a rounded structure, suggestive of a pseudocyst containing Toxoplasma gondii bradyzoites. However, serological tests were negative for immunoglobulin G and immunoglobulin M. CONCLUSIONS: Bronchoscopy is a minimally invasive, effective diagnostic and therapeutic method. Despite the fact that the Toxoplasma pseudocyst in the present case was not the cause of the patient's comorbidities, bronchoscopy with transbronchial biopsy allowed for an incidental diagnosis of a Toxoplasma pseudocyst with minimal invasiveness. PMID- 27658583 TI - Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways. AB - BACKGROUND: Several studies show that bone marrow (BM) microenvironment and hypoxia condition can promote the survival of leukemic cells and induce resistance to anti-leukemic drugs. However, the molecular mechanism for chemoresistance by hypoxia is not fully understood. METHODS: In the present study, we investigated the effect of hypoxia on resistance to two therapies, methotrexate (MTX) and prednisolone (PRD), in two cell models for acute lymphoblastic leukemia (ALL). To look for an implication of hypoxia in chemoresistance, cell viability, total cell density and cell proliferation were analyzed. Survival and death signaling pathways were also screened by "reverse phase protein array" (RPPA) and western blotting experiments conducted on selected proteins to confirm the results. RESULTS: We found that hypoxia promotes chemoresistance in both ALL cell lines. The induction of drug-resistance by hypoxia was not associated with an increase in total cell density nor an increase in cell proliferation. Using RPPA, we show that chemoresistance induced by hypoxia was mediated through an alteration of cell death signaling pathways. This protective effect of hypoxia seems to occur via a decrease in pro-apoptotic proteins and an increase in anti-apoptotic proteins. The results were confirmed by immunoblotting. Indeed, hypoxia is able to modulate the expression of anti apoptotic proteins independently of chemotherapy while a pro-apoptotic signal induced by a chemotherapy is not modulated by hypoxia. CONCLUSIONS: Hypoxia is a factor in leukemia cell resistance and for two conventional chemotherapies modulates cell death signaling pathways without affecting total cell density or cell proliferation. PMID- 27658584 TI - Stimulating effect of normal-dosing of fibrates on cell proliferation: word of warning. AB - BACKGROUND: Fibrates are widely used hypolipidemic drugs, which serve as ligand of peroxisome proliferator-activated receptor alpha (PPARalpha). Recently, they have also been considered as potential anticancer agents. We studied effect of fibrates treatment on cell proliferation, expression of CYP2J2 and concomitant changes in expression of cell cycle regulatory proteins in three different human cell lines: HEK293, HepG2, and HT-29. METHODS: We used WST-1 viability test, western blot and immunocytochemistry for detection of proteins of interests and analysis of cell cycle. RESULTS: Our results showed that at lower concentrations of all tested fibrates, viability of all tested cell lines is increased, whereas at higher concentrations, repression is apparent. Unfortunately, the viability of tested cells is predominantly increased in a range of concentration which is reached in patient plasma. This phenomenon is accompanyed by elevation of CYP2J2, increased number of cyclin E-positive cells and decreased number of Cdc25A positive cells in all tested cell lines, and elevated cyclin A expression in HepG2 and HT-29. These changes are concentration-dependent. We suppose that increased level of CYP2J2 could explain enhanced cell proliferation in lower concentration of fibrates. CONCLUSION: Based on our results, we suggested there is no anti-cancer effect of fibrates in tested carcinoma cell lines. PMID- 27658585 TI - Using an Artificial Neural Bypass to Restore Cortical Control of Rhythmic Movements in a Human with Quadriplegia. AB - Neuroprosthetic technology has been used to restore cortical control of discrete (non-rhythmic) hand movements in a paralyzed person. However, cortical control of rhythmic movements which originate in the brain but are coordinated by Central Pattern Generator (CPG) neural networks in the spinal cord has not been demonstrated previously. Here we show a demonstration of an artificial neural bypass technology that decodes cortical activity and emulates spinal cord CPG function allowing volitional rhythmic hand movement. The technology uses a combination of signals recorded from the brain, machine-learning algorithms to decode the signals, a numerical model of CPG network, and a neuromuscular electrical stimulation system to evoke rhythmic movements. Using the neural bypass, a quadriplegic participant was able to initiate, sustain, and switch between rhythmic and discrete finger movements, using his thoughts alone. These results have implications in advancing neuroprosthetic technology to restore complex movements in people living with paralysis. PMID- 27658587 TI - Development and psychometric testing of Holistic Clinical Assessment Tool (HCAT) for undergraduate nursing students. AB - BACKGROUND: A major focus in nursing education is on the judgement of clinical performance, and it is a complex process due to the diverse nature of nursing practice. A holistic approach in assessment of competency is advocated. Difficulties in the development of valid and reliable assessment measures in nursing competency have resulted in the development of assessment instruments with an increase in face and content validity, but few studies have tested these instruments psychometrically. It is essential to develop a holistic assessment tool to meet the needs of the clinical education. The study aims to develop a Holistic Clinical Assessment Tool (HCAT) and test its psychometric properties. METHODS: The HCAT was developed based on the systematic literature review and the findings of qualitative studies. An expert panel was invited to evaluate the content validity of the tool. A total of 130 final-year nursing undergraduate students were recruited to evaluate the psychometric properties (i.e. factor structure, internal consistency and test-retest reliability) of the tool. RESULTS: The HCAT has good content validity with content validity index of .979. The exploratory factor analysis reveals a four-factor structure of the tool. The internal consistency and test-retest reliability of the HCAT are satisfactory with Cronbach alpha ranging from .789 to .965 and Intraclass Correlation Coefficient ranging from .881 to .979 for the four subscales and total scale. CONCLUSIONS: HCAT has the potential to be used as a valid measure to evaluate clinical competence in nursing students, and provide specific and ongoing feedback to enhance the holistic clinical learning experience. In addition, HCAT functions as a tool for self-reflection, peer-assessment and guides preceptors in clinical teaching and assessment. PMID- 27658586 TI - Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells. AB - BACKGROUND: Hsp90 proteins are important therapeutic targets for many anti-cancer drugs in clinical trials. Geldanamycin (GA) was identified as the first natural inhibitor of Hsp90, increasing evidence suggests that GA was not a good choice for clinical trials. In this study, we investigated two new non-benzoquinone geldanamycin analogs of Hsp90 inhibitors, DHQ3 and 17-demethoxy-reblastatin (17 DR), to explore the molecular mechanisms of their anti-cancer activity in vivo and vitro. METHODS: MTT and colony formation assays were used to measure cell viability. Flow cytometry, DAPI staining, ATP assay, electron microscopy, western blots, siRNAs transfection and immunofluorescence were used to determine the molecular mechanism of DHQ3- or 17-DR-induced different forms of death in human breast cancer MDA-MB-231 cells. Malachite green reagent was used to measure ATPase activity of the analogs. RESULTS: DHQ3 and 17-DR presented efficiently inhibitory effect in MDA-MB-231 cell lines, and DHQ3 induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade. And DHQ3-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), but not by a caspase inhibitor z-VAD-fmk. On the other hand, 17-DR induced apoptosis in MDA-MB 231 cells, indicating a caspase-dependent killing mechanism. We further demonstrated that down-regulation of RIP1 and RIP3 by siRNA protected against DHQ3 but not 17-DR induced cell death. These results were confirmed by electron microscopy. DHQ3 and 17-DR induced the degradation of Hsp90 client proteins, and they showed strong antitumor effects in MDA-MB-231 cell-xenografted nude mice. CONCLUSIONS: These findings supported that DHQ3 and 17-DR induce different forms of death in some cancer cell line via activation of different pathways. All of the results provided evidence for its anti-tumorigentic action with low hepatotoxicity in vivo, making them promising anti-breast cancer agents. PMID- 27658588 TI - Characterization of Pv92, a Novel Merozoite Surface Protein of Plasmodium vivax. AB - The discovery and understanding of antigenic proteins are essential for development of a vaccine against malaria. In Plasmodium falciparum, Pf92 have been characterized as a merozoite surface protein, and this protein is expressed at the late schizont stage, but no study of Pv92, the orthologue of Pf92 in P. vivax, has been reported. Thus, the protein structure of Pv92 was analyzed, and the gene sequence was aligned with that of other Plasmodium spp. using bioinformatics tools. The recombinant Pv92 protein was expressed and purified using bacterial expression system and used for immunization of mice to gain the polyclonal antibody and for evaluation of antigenicity by protein array. Also, the antibody against Pv92 was used for subcellular analysis by immunofluorescence assay. The Pv92 protein has a signal peptide and a sexual stage s48/45 domain, and the cysteine residues at the N-terminal of Pv92 were completely conserved. The N-terminal of Pv92 was successfully expressed as soluble form using a bacterial expression system. The antibody raised against Pv92 recognized the parasites and completely merged with PvMSP1-19, indicating that Pv92 was localized on the merozoite surface. Evaluation of the human humoral immune response to Pv92 indicated moderate antigenicity, with 65% sensitivity and 95% specificity by protein array. Taken together, the merozoite surface localization and antigenicity of Pv92 implicate that it might be involved in attachment and invasion of a merozoite to a new host cell or immune evasion during invasion process. PMID- 27658589 TI - Hemozoin Pigment: An Important Tool for Low Parasitemic Malarial Diagnosis. AB - Low parasitemic condition in malaria remains a diagnostic challenge; as the available diagnostic methods failed to detect. Currently, hemozoin (Hz) pigment is gaining attention in the diagnosis of malaria. The major drawback is ease of detection of Hz in routine practice. A pilot study was conducted to evaluate the role of Hz pigment and to compare the performance of quantitative buffy coat assay (QBC) and PCR in such conditions. Clinically suspected cases of malaria were examined by both Giemsa stain and immunochromatographic test (ICT). Samples positive by ICT and negative by Giemsa stain were further examined by nested PCR targeting 18S rRNA and QBC for the presence of malaria parasites and pigments. Thirty blood samples fulfilled the inclusion criteria out of which 23 were Plasmodium vivax (Pv), 4 Plasmodium falciparum (Pf), and 3 mixed (Pv and Pf) by immunochromatographic test. Twenty-one out of 30 (70%) were positive by nested PCR in comparison to 25/30 (83%) by QBC. Samples containing both malaria parasites and Hz pigment by QBC completely showed concordance with the PCR result. However, 61% of total samples containing only Hz pigment were observed positive by PCR. Hz pigment remains an important tool for malaria diagnosis. Identification of leukocytes containing pigments by QBC not only indicates recent malarial infections but also puts light on severity of the disease. QBC assay is a rapid, highly sensitive, and cost-effective method to detect malaria parasites and Hz pigment especially in low parasitemic conditions. PMID- 27658590 TI - Impact of Irrigation Extension on Malaria Transmission in Simret, Tigray, Ethiopia. AB - Poor subsistence farmers who live in a semi-arid area of northern Ethiopia build irrigation systems to overcome water shortages. However, there is a high risk of malaria transmission when increased standing water provides more favorable habitats for mosquito breeding. This is a serious problem because there are many barriers to malaria control measures and health care systems in the area. Using a causal loop diagram and computer simulations, the author attempted to visually illustrate positive and negative feedbacks between mosquito and human populations in the context of Simret, which is a small village located in northern Ethiopia and is generally considered a malaria-free area. The simulation results show that the number of infectious mosquitos increases to 17,215 at its peak, accounting for 3.5% of potentially dangerous mosquitos. At the same time, the number of sick people increases to 574 at its peak, accounting for 15% of local population. The malaria outbreak is controlled largely because of a fixed number of vulnerable people or local population that acts as an intermediate host. PMID- 27658591 TI - Characteristics of Imported Malaria and Species of Plasmodium Involved in Shandong Province, China (2012-2014). AB - Malaria remains a serious public health problem in Shandong Province, China; therefore, it is important to explore the characteristics of the current malaria prevalence situation in the province. In this study, data of malaria cases reported in Shandong during 2012-2014 were analyzed, and Plasmodium species were confirmed by smear microscopy and nested-PCR. A total of 374 malaria cases were reported, 80.8% of which were reported from 6 prefectures. Of all cases, P. falciparum was dominant (81.3%), followed by P. vivax (11.8%); P. ovale and P. malariae together accounted for 6.4% of cases. Notably, for the first time since 2012, no indigenous case had been reported in Shandong Province, a situation that continued through 2014. Total 95.2% of cases were imported from Africa. The ratio of male/female was 92.5:1, and 96.8% of cases occurred in people 20-54 years of age. Farmers or laborers represented 77.5% of cases. No significant trends of monthly pattern were found in the reported cases. All patients were in good condition after treatment, except for 3 who died. These results indicate that imported malaria has increased significantly since 2012 in Shandong Province, especially for P. falciparum, and there is an emergence of species diversity. PMID- 27658592 TI - Antiplasmodial and Cytotoxic Activities of Toad Venoms from Southern Amazon, Brazil. AB - The drug-resistance of malaria parasites is the main problem in the disease control. The huge Brazilian biodiversity promotes the search for new compounds, where the animal kingdom is proving to be a promising source of bioactive compounds. The main objective of this study was to evaluate the antiplasmodial and cytotoxic activity of the compounds obtained from the toad venoms of Brazilian Amazon. Toad venoms were collected from the secretion of Rhinella marina and Rhaebo guttatus in Mato Grosso State, Brazil. The powder was extracted at room temperature, yielding 2 extracts (RG and RM) and a substance ('1') identified as a bufadienolide, named telocinobufagin. Growth inhibition, intraerythrocytic development, and parasite morphology were evaluated in culture by microscopic observations of Giemsa-stained thin blood films. Cytotoxicity was determined against HepG2 and BGM cells by MTT and neutral red assays. The 2 extracts and the pure substance ('1') tested were active against chloroquine resistant Plasmodium falciparum strain, demonstrating lower IC50 values. In cytotoxic tests, the 2 extracts and substance '1' showed pronounced lethal effects on chloroquine-resistant P. faciparum strain and low cytotoxic effect, highlighting toad parotoid gland secretions as a promising source of novel lead antiplasmodial compounds. PMID- 27658594 TI - Identifying Novel B Cell Epitopes within Toxoplasma gondii GRA6. AB - The study of antigenic epitopes from Toxoplasma gondii has not only enhanced our understanding of the structure and function of antigens, the reactions between antigens and antibodies, and many other aspects of immunology, but it also plays a significant role in the development of new diagnostic reagents and vaccines. In the present study, T. gondii GRA6 epitopes were identified using bioinformatics tools and a synthetic peptide technique. The potential B cell epitopes of GRA6 predicted by bioinformatics tools concentrated upon 3 regions of GRA6, 1-20 aa, 44-103 aa, and 172-221 aa. Ten shorter peptides from the 3 regions were synthesized and assessed by ELISA using pig sera from different time points after infection. Three of the 10 peptides (amino acids 44-63, 172-191, and 192-211) tested were recognized by all sera and determined to be immunodominant B-cell epitopes of GRA6. The results indicated that we precisely and accurately located the T. gondii GRA6 epitopes using pig sera collected at different time points after infection. The identified epitopes may be very useful for further studies of epitope-based vaccines and diagnostic reagents. PMID- 27658593 TI - Molecular Identification of Cryptosporidium Species from Pet Snakes in Thailand. AB - Cryptosporidium is an important pathogen causing gastrointestinal disease in snakes and is distributed worldwide. The main objectives of this study were to detect and identify Cryptosporidium species in captive snakes from exotic pet shops and snake farms in Thailand. In total, 165 fecal samples were examined from 8 snake species, boa constrictor (Boa constrictor constrictor), corn snake (Elaphe guttata), ball python (Python regius), milk snake (Lampropeltis triangulum), king snake (Lampropeltis getula), rock python (Python sebae), rainbow boa (Epicrates cenchria), and carpet python (Morelia spilota). Cryptosporidium oocysts were examined using the dimethyl sulfoxide (DMSO) modified acid-fast staining and a molecular method based on nested-PCR, PCR-RFLP analysis, and sequencing amplification of the SSU rRNA gene. DMSO-modified acid fast staining revealed the presence of Cryptosporidium oocysts in 12 out of 165 (7.3%) samples, whereas PCR produced positive results in 40 (24.2%) samples. Molecular characterization indicated the presence of Cryptosporidium parvum (mouse genotype) as the most common species in 24 samples (60%) from 5 species of snake followed by Cryptosporidium serpentis in 9 samples (22.5%) from 2 species of snake and Cryptosporidium muris in 3 samples (7.5%) from P. regius. PMID- 27658595 TI - Seroprevalence and Spatial Distribution of Toxoplasmosis in Sheep and Goats in North-Eastern Region of Pakistan. AB - Toxoplasmosis is a protozoan disease that is caused by Toxoplasma gondii in livestock and humans. Due to its medical and veterinary importance, it is essential to study the seroprevalence of T. gondii infection among humans and animals in various parts of the world. The major objective of this study was to determine the seroprevalence and spatial distribution of toxoplasmosis in small ruminants (sheep and goats) of north-eastern region, Pakistan. A total of 1,000 animals comprising of sheep (n=470) and goats (n=530) were examined for T. gondii infection by using ELISA. An epidemiological data was collected in the form of questionnaire. A surface has been generated by using method of interpolation in Arc GIS with the help of IDW (inverse distance weight). The results showed higher seroprevalence of T. gondii in goats (42.8%) as compared to sheep (26.2%). The seroprevalence was higher in females as compared to males in all examined ruminants. Similarly, there is a wide variation in the seroprevalence of T. gondii in different breeds of sheep and goats showing higher seroprevalence in Teddy (52.8%) and Damani breed (34.5%) of goat and sheep's, respectively. The geographical and spatial distribution of T. gondii shows that it is widely distributed in different parts of the north-eastern region of Pakistan. Our results suggest widespread environmental contamination with T. gondii oocysts. It suggests us that small ruminants could be a potentially important source of T. gondii infection if their infected meat is consumed undercooked. PMID- 27658596 TI - Isolation and Genotyping of Acanthamoeba spp. as Neglected Parasites in North of Iran. AB - Acanthamoeba, a free-living amoeba, is widely distributed in the environment, water sources, soil, dust, and air. It can cause keratitis in contact lens wearers with poor hygiene and also fatal granulomatous amebic encephalitis (GAE) in immunocompromised hosts. The aim of this study was to gain some insights into the distribution and genotypes of the potentially pathogenic species of Acanthamoeba present in water sources in north of Iran. Total 43 Acanthamoeba species were isolated from 77 water samples taken from different water sources within the Mazandaran province in Northern Iran (Sari city and suburbs). Isolates were identified based on cyst and trophozoite morphological characteristics as well genetics. PCR fragments corresponding to the small-subunit 18S rRNA gene were sequenced for 20 of 43 positive isolates. The results revealed that 83.3% of sequenced isolates belonged to the T4 genotype and the rest belonged to the T2 genotype. Our results indicated that Acanthamoeba is widely distributed in Sari city. As the incidence in Iran of amoebic keratitis has increased in recent years, the exact estimation of the prevalence of this amoeba and its predominant genotype may play a crucial role in prevention of the disease. Sari city has several rivers, seashores, and natural recreational amenities, which attract visitors during the year. This is the first report of Acanthamoeba genotypes from water sources in Sari city, Mazandaran province of Iran, and the results suggest that more attention is needed to protect the visiting population and immunocompromised individuals. PMID- 27658597 TI - Subtype Distribution of Blastocystis in Communities along the Chao Phraya River, Thailand. AB - Blastocystis is a common zoonotic enteric protozoan that has been classified into 17 distinct subtypes (STs). A cross-sectional study was conducted to determine the prevalence and subtype distributions of Blastocystis in villagers living along the Chao Phraya River, Ayutthaya Province, Thailand, and to assess the risk of zoonotic infection. In total, 220 stool samples were collected, and DNA was extracted. PCR and sequencing were performed with primers targeting the small subunit ribosomal RNA (SSU rRNA) genes. Blastocystis was present in 5.9% (13/220) of samples, and ST3 (5.0%; 11/220) was the predominant subtype, followed by ST2 (0.45%; 1/220) and ST6 (0.45%; 1/220). Phylogenetic trees were constructed with the maximum-likelihood method based on the Hasegawa-Kishino-Yano + G + I model, neighbor-joining, and maximum parsimony methods. The percentage of bootstrapped trees in which the associated taxa clustered together was relatively high. All the sequences of the Blastocystis-positive samples (KU051524-KU051536) were closely related to those from animals (pig, cattle, and chicken), indicating a zoonotic risk. Therefore, the villagers require proper health education, especially regarding the prevention of parasitic infection, to improve their personal hygiene and community health. Further studies are required to investigate the Blastocystis STs in the animals living in these villages. PMID- 27658598 TI - Identification of a Novel Microtubule-Binding Protein in Giardia lamblia. AB - Giardia lamblia is a protozoan that causes diarrheal diseases in humans. Cytoskeletal structures of Giardia trophozoites must be finely reorganized during cell division. To identify Giardia proteins which interact with microtubules (MTs), Giardia lysates were incubated with in vitro-polymerized MTs and then precipitated by ultracentifugation. A hypothetical protein (GL50803_8405) was identified in the precipitated fraction with polymerized MTs and was named GlMBP1 (G. lamblia microtubule-binding protein 1). Interaction of GlMBP1 with MTs was confirmed by MT binding assays using recombinant GlMBP1 (rGlMBP1). In vivo expression of GlMBP1 was shown by a real-time PCR and western blot analysis using anti-rGlMBP1 antibodies. Transgenic G. lamblia trophozoites were constructed by integrating a chimeric gene encoding hemagglutinin (HA)-tagged GlMBP1 into a Giardia chromosome. Immunofluorescence assays of this transgenic G. lamblia, using anti-HA antibodies, revealed that GlMBP1 mainly localized at the basal bodies, axonemes, and median bodies of G. lamblia trophozoites. This result indicates that GlMBP1 is a component of the G. lamblia cytoskeleton. PMID- 27658599 TI - Prevalence of Soil-Transmitted Helminths and Molecular Clarification of Hookworm Species in Ethnic Ede Primary Schoolchildren in Dak Lak Province, Southern Vietnam. AB - To know the infection status of helminths in primary schoolchildren of southern parts of Vietnam, we performed an epidemiological study in Krong Pac district, Dak Lak Province, Vietnam. A total of 1,206 stool specimens were collected from ethnic Ede schoolchildren in 4 primary schools in 2015 and examined by the Kato Katz technique. In addition, stool cultures were done by the Harada-Mori method to obtain hookworm larvae and then to clarify the species of hookworms infected. The results showed that the helminth infection rate was 25.0%, including 2.0% Ascaris lumbricoides, 0.33% Trichuris trichiura, and 22.8% hookworm infections. The average intensity of infection was 102.0 eggs per gram of feces (EPG) for Ascaris, 36.0 EPG for Trichuris, and 218.0 EPG for hookworms. ITS1 gene sequences of the hookworm larvae were identical with those of Necator americanus (100% homology) reported in GenBank. It has been confirmed in this study that the hookworm, N. americanus, is a dominant helminth species infected in primary schoolchildren of a southern part of Vietnam. Public health attention is needed for control of hookworm infections among schoolchildren in surveyed areas of Vietnam. PMID- 27658600 TI - In Vitro Schistosomicidal Activity of Phytol and Tegumental Alterations Induced in Juvenile and Adult Stages of Schistosoma haematobium. AB - There is renewed interest in natural products as a starting point for discovery of drugs for schistosomiasis. Recent studies have shown that phytol reveals interesting in vivo and in vitro antischistosomal properties against Schistosoma mansoni adult worms. Here, we report the in vitro antischistosomal activity of phytol against Schistosoma haematobium juvenile and adult worms and alterations on the tegumental surface of the worms by means of scanning electron microscopy. The assay, which was carried out with 6 concentrations (25, 50, 75, 100, 125, and 150 MUg/ml) of phytol, has shown a promising activity in a dose and time dependent manner. There was a significant decline in the motility of the worms and a mortality rate of 100% was found at 48 hr after they had been exposed to phytol in the concentration of 150 MUg/ml. Male worms were more susceptible. On the ultrastructural level, phytol also induced tegumental peeling, disintegration of tubercles and spines in addition to morphological disfiguring of the oral and ventral suckers. This report provides the first evidence that phytol is able to kill S. haematobium of different ages, and emphasizes that it is a promising natural product that could be used for development of a new schistosomicidal agent. PMID- 27658601 TI - Two Echinostome Species, Pegosomum bubulcum and Nephrostomum ramosum (Digenea: Echinostomatidae), from an Eastern Cattle Egret, Bubulcus ibis coromandus, in Republic of Korea. AB - We describe 2 echinostome species recovered from an Eastern cattle egret, Bubulcus ibis coromandus, from Cheongju-si (city), Chungcheongbuk-do (province), Korea. Total 72 Pegosomum bubulcum specimens were recovered from the bile duct. They were 7,566*2,938 MUm in average size and had 27 collar spines with vitelline extension from anterior 1/3 level of the esophagus to mid-level of the posterior testis as characteristic features. Total 9 specimens of Nephrostomum ramosum were recovered in the small intestines of the bird. They were ribbon-shaped, 11,378*2,124 MUm in average size, and morphologically variable in some organs, i.e., the number of collar spines (47-50), the shape of ovary and testes, and the extension of vitelline follicles. These morphological variations observed in a single host indicated that these features are not critical for the classification of Nephrostomum species and thus were reconsidered taxonomically as synonym of N. ramosum. This study is the first report documenting and describing both flukes and their associated genera in Korea. PMID- 27658602 TI - Pygidiopsis summa (Digenea: Heterophyidae): Status of Metacercarial Infection in Mullets from Coastal Areas in the Republic of Korea. AB - To know the infection status of zoonotic trematode metacercariae in brackish water fish, we surveyed mullets collected from 18 coastal areas in the Republic of Korea. The metacercariae of Pygidiopsis summa were detected in 236 (68.2%) out of 346 mullets examined. They were found in mullets from 15 areas except for those from Boseong-gun (Jeollanam-do), Pohang-si, and Uljin-gun (Gyeongsangbuk do). Especially in mullets from Taean-gun (Chungcheongnam-do) and Geoje-si (Gyeongsangnam-do), their prevalences were 100% and 95.5%, and the average metacercarial density was more than 1,000 per fish. They were also detected in mullets from 3 coastal lakes, Gyeongpoho, Songjiho, and Hwajinpoho, in Gangwon do, and their average densities were 419, 147, and 672 per infected fish, respectively. The metacercariae of 5 other heterophyid species, including Heterophyes nocens, Heterophyopsis continua, Metagonimus sp., Stictodora fuscata, and Stictodora lari, were found in the mullets examined. The metacercariae of H. nocens were detected in 66.7, 100, 28.6, 81.6, 3.9, 61.5, and 27.3% of mullets from Muan-gun, Shinan-gun, Haenam-gun, Gangjin-gun, and Boseong-gun (Jeollanam do), Hadong-gun, and Geoje-si (Gyeongsangnam-do), and their metacercarial intensities were 64, 84, 119, 99, 1, 24, and 24 per fish infected, respectively. From the above results, it has been confirmed that P. summa metacercariae are heavily infected in mullets from coastal areas of Korea. It is suggested that residents who frequently consume raw mullet dish can be easily infected with heterophyid flukes. PMID- 27658603 TI - Molecular Detection of Spirometra decipiens in the United States. AB - The genus Spirometra belongs to the family Diphyllobothriidae and order Pseudophyllidea, and includes intestinal parasites of cats and dogs. In this study, a plerocercoid labeled as Spirometra mansonoides from the USA was examined for species identification and phylogenetic analysis using 2 complete mitochondrial genes, cytochrome c oxidase I (cox1) and NADH dehydrogenase subunit 3 (nad3). The cox1 sequences (1,566 bp) of the plerocercoid specimen (USA) showed 99.2% similarity to the reference sequences of the plerocercoid of Korean Spirometra decipiens (GenBank no. KJ599679), and 99.1% similarity in regard to nad3 (346 bp). Phylogenetic tree topologies generated using 4 analytical methods were identical and showed high confidence levels with bootstrap values of 1.00, 100%, 100%, and 100% for Bayesian inference (BI), maximum-likelihood (ML), neighbor-joining (NJ), and maximum parsimony (MP) methods, respectively. Representatives of Diphyllobothrium and Spirometra species formed a monophyletic group, and the sister-genera status between these species was well supported. Trapezoic proglottids in the posterior 1/5 region of an adult worm obtained from an experimentally infected cat were morphologically examined. The outer uterine loop of the uterus coiling characteristically consisted of 2 complete turns. The results clearly indicated that the examined Spirometra specimen from the USA matched to S. decipiens very well, and indicated possible presence of the life cycle of this species in this region. PMID- 27658604 TI - Catenotaenia dendritica (Cestoda: Catenotaeniidae) and Three Ectoparasite Species in the Red Squirrel, Sciurus vulgaris, from Cheongju, Korea. AB - Parasites are recorded from the red squirrel, Sciurus vulgaris, from Cheongju, the Republic of Korea. A total of 5 road-killed squirrels were thoroughly examined for internal and external parasites from November 2011 to May 2014. Total 4 parasite species, including 1 tapeworm and 3 ectoparasite species were recovered. They were morphologically identified as Catenotaenia dendritica (Cestoda: Catenotaeniidae), Hirstionyssus sciurinus, Leptotrombidium pallidum, and Ceratophyllus (Monopsyllus) indages. Among them, C. dendritica and H. sciurinus are recorded for the first time in the Korean parasite fauna. In addition, the possibility that the red squirrel could act as a reservoir host for a zoonotic disease like tsutsugamushi disease with L. pallidum as its vector has been raised. PMID- 27658605 TI - Increased Expression of TGF-beta1 in Correlation with Liver Fibrosis during Echinococcus granulosus Infection in Mice. AB - To investigate the potential role of transforming growth factor (TGF)-beta1 in liver fibrosis during Echinococcus granulosus infection, 96 BALB/c mice were randomly divided into 2 groups, experimental group infected by intraperitoneal injection with a metacestode suspension and control group given sterile physiological saline. The liver and blood samples were collected at days 2, 8, 30, 90, 180, and 270 post infection (PI), and the expression of TGF-beta1 mRNA and protein was determined by real-time quantitative RT-PCR and ELISA, respectively. We also evaluated the pathological changes in the liver during the infection using hematoxylin and eosin (H-E) and Masson staining of the liver sections. Pathological analysis of H-E stained infected liver sections revealed liver cell edema, bile duct proliferation, and structural damages of the liver as evidenced by not clearly visible lobular architecture of the infected liver, degeneration of liver cell vacuoles, and infiltration of lymphocytes at late stages of infection. The liver tissue sections from control mice remained normal. Masson staining showed worsening of liver fibrosis at the end stages of the infection. The levels of TGF-beta1 did not show significant changes at the early stages of infection, but there were significant increases in the levels of TGF beta1 at the middle and late stages of infection (P<0.05). RT-PCR results showed that, when compared with the control group, TGF-beta1 mRNA was low and comparable with that in control mice at the early stages of infection, and that it was significantly increased at day 30 PI and remained at high levels until day 270 PI (P<0.05). The results of this study suggested that increased expression of TGF beta1 during E. granulosus infection may play a significant role in liver fibrosis associated with E. granulosus infection. PMID- 27658606 TI - Electron Microscopic Alterations in Pediculus humanus capitis Exposed to Some Pediculicidal Plant Extracts. AB - Head lice, Pediculus humanus capitis, infestation is an important public health problem in Egypt. Inadequate application of topical pediculicides and the increasing resistance to the commonly used pediculicides made the urgent need for the development of new agents able to induce irreversible changes in the exposed lice leading to their mortality. The aim of the present work is to evaluate pediculicidal efficacy of some natural products such as olive oil, tea tree oil, lemon juice, and ivermectin separately in comparison with tetramethrin-piperonyl butoxide (licid), as a standard pediculicide commonly used in Egypt. The effects of these products were evaluated by direct observation using dissecting and scanning electron microscopes (SEM). Results showed that after 1 hr exposure time in vitro, absolute (100%) mortalities were recorded after exposure to 1% ivermectin and fresh concentrate lemon juice. The mortalities were decreased to 96.7% after exposure to tea tree oil. Very low percentage of mortality (23.3%) was recorded after 1 hr of exposure to extra virgin olive oil. On the other hand, the reference pediculicide (licid) revealed only mortality rate of 93.3%. On the contrary, no mortalities were recorded in the control group exposed to distilled water. By SEM examination, control lice preserved outer smooth architecture, eyes, antenna, respiratory spiracles, sensory hairs, and legs with hook-like claws. In contrast, dead lice which had been exposed to pediculicidal products showed damage of outer smooth architecture, sensory hairs, respiratory spiracles and/or clinching claws according to pediculicidal products used. PMID- 27658607 TI - A Case of Ancylostoma ceylanicum Infection Occurring in an Australian Soldier Returned from Solomon Islands. AB - A 26-year-old male member of the Australian Defense Force presented with a history of central abdominal pain of 4 weeks duration and peripheral eosinophilia consistent with eosinophilic enteritis. Acute hookworm disease was diagnosed as the cause. Adult worms recovered from feces after therapy with albendazole were morphologically consistent with Ancylostoma ceylanicum. As the patient had been deployed with the Regional Assistance Mission to Solomon Islands for 6 months prior to this presentation, it is very likely that the A. ceylanicum was acquired in Solomon Islands. Until now, it has been assumed that any Ancylostoma spp. recovered from humans in Solomon Islands is A. duodenale. However, this case demonstrates that human hookworm infection acquired in the Solomon Islands could be caused by A. ceylanicum. PMID- 27658608 TI - Stellantchasmus falcatus (Digenea: Heterophyidae) in Cambodia: Discovery of Metacercariae in Mullets and Recovery of Adult Flukes in an Experimental Hamster. AB - Stellantchasmus falcatus (Digenea: Heterophyidae) is first reported from Cambodia through recovery of the metacercariae from mullet fish and adult flukes from an experimentally infected hamster. We purchased 7 mullets, Chelon macrolepis, in a local market of Phnom Penh, Cambodia, and each of them was examined by the artificial digestion method on May 2010. The metacercariae of S. falcatus were detected in all mullets (100%) examined, and their average density was 177 per fish. They were elliptical, 220*168 MUm in average size. They were orally infected to an hamster to obtain adult flukes. Adults recovered at day 10 post infection were observed with a light microscope and a scanning electron microscope (SEM). They were small, 450*237 MUm in average size, had a small oral sucker (41*50 MUm), subglobular pharynx (29*21 MUm), slender esophagus (57 MUm), long and thick-walled expulsor (119*32 MUm), spherical ovary (58*69 MUm), and 2 ovoid testes (right: 117*74 MUm; left: 114*63 MUm). Eggs were small, yellow, and 23*12 MUm in average size. In SEM observations, tegumental spines were densely distributed on the whole tegument, and single small type I sensory papillae were distributed around the lip of oral sucker. The small ventral sucker was dextrally located and had 8 type I sensory papillae on the left margin. It has been first confirmed in the present study that the mullet, C. macrolepis, is playing the role of a second intermediate host of S. falcatus in Cambodia. PMID- 27658609 TI - First Record of Paramphistomes Fischoederius cobboldi and Paramphistomum epiclitum Detected in Bovine Rumen from a Local Market of Savannakhet Province, Lao PDR. AB - In the present study, we report on the occurrence of paramphistomes, Fischoederius cobboldi and Paramphistomum epiclitum, in Lao PDR with the basis of molecular data. Parasite materials were collected from bovines bred in Ban Lahanam area, Savannakhet Province, Lao PDR at Lahanam public market. Morphological observations indicated 2 different species of paramphistomes. The mitochondrial gene cox1 of the specimens was successfully amplified by PCR and DNA sequencing was carried out for diagnosis of 11 specimens. Pairwise alignment of cox1 sequences were performed and confirmed F. cobboldi and P. epiclitum infecting bovines in Laos. Although there were many limiting points, as the small number of worm samples, and the restricted access of the animal host materials, we confirmed for the first time that 2 species of paramphistomes, F. cobboldi and P. epiclitum, are distributed in Lao PDR. More studies are needed to confirm the paramphistome species present in Savannakhet and its hosts to clear the natural history of these parasites of ruminants in the region and measure the impact of this parasite infection in the life and health of the local people. PMID- 27658611 TI - Improving psychotropic medication use among persons with dementia. AB - The use of psychotropic medication among persons with dementia (PWD) both in nursing home (Wetzels et al., 2011) and community settings (Maust et al., 2016) far exceeds what might be expected based on their limited evidence for benefit (Kales et al., 2015). This relatively high use persists despite years of evidence about the potential harms associated with their use in older adults generally and PWD in particular (e.g. Wang et al., 2001; Schneider et al., 2005). However, the solution to relatively high psychotropic use is not to end all psychotropic use, as there are individual patients for whom use of such medication is appropriate. For example, a policy that defines all antipsychotic use as inappropriate may simply lead to increased use of alternatives with even less evidence of benefit, as suggested by the response to antipsychotics' black box warning in the United States (Kales et al., 2011). PMID- 27658610 TI - Detecting Suicide Risk Among College Students: A Test of the Predictive Validity of the Modified Emotional Stroop Task. AB - Detecting suicide risk among nonclinical populations is challenging due to low base rates and the help-negation tendency of at-risk individuals. The current longitudinal study investigated the predictive validity of the modified emotional Stroop task (EST) by conducting a follow-up study of 197 students who participated in a study by Chung and Jeglic (2016). The EST latencies for suicide related cues and past suicidal behaviors were the only significant predictors of suicide risk. The findings of this study provide preliminary support for the use of the EST as part of a suicide risk screening battery that could add to the detection of suicide risk. PMID- 27658612 TI - Bioink properties before, during and after 3D bioprinting. AB - Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction. PMID- 27658613 TI - Thermal protein unfolding by differential scanning calorimetry and circular dichroism spectroscopy Two-state model versus sequential unfolding. AB - Thermally-induced protein unfolding is commonly described with the two-state model. This model assumes only two types of protein molecules in solution, the native (N) and the denatured, unfolded (U) protein. In reality, protein unfolding is a multistep process, even if intermediate states are only sparsely populated. As an alternative approach we explore the Zimm-Bragg theory, originally developed for the alpha-helix-to-random coil transition of synthetic polypeptides. The theory includes intermediate structures with concentrations determined by the cooperativity of the unfolding reaction. We illustrate the differences between the two-state model and the Zimm-Bragg theory with measurements of apolipoprotein A-1 and lysozyme by differential scanning calorimetry (DSC) and CD spectroscopy. Nine further protein examples are taken from the literature. The Zimm-Bragg theory provides a perfect fit of the calorimetric unfolding transitions for all proteins investigated. In contrast, the transition curves and enthalpies predicted by the two-state model differ considerably from the experimental results. Apolipoprotein A-1 is ~50% alpha-helical at ambient temperature and its unfolding follows the classical alpha-helix-to-random coil equilibrium. The unfolding of proteins with little alpha-helix content, such as lysozyme, can also be analyzed with the Zimm-Bragg theory by introducing the concept of 'folded' and 'unfolded' peptide units assuming an average unfolding enthalpy per peptide unit. DSC is the method of choice to measure the unfolding enthalpy, , but CD spectroscopy in combination with the two-state model is often used to deduce the unfolding enthalpy. This can lead to erroneous result. Not only are different enthalpies required to describe the CD and DSC transition curves but these values deviate distinctly from the experimental result. In contrast, the Zimm-Bragg theory predicts the DSC and CD unfolding transitions with the same set of parameters. PMID- 27658615 TI - Sumoylation of IkB attenuates NF-kB-induced nitrosative stress at rostral ventrolateral medulla and cardiovascular depression in experimental brain death. AB - BACKGROUND: Small ubiquitin-related modifier (SUMO) is a group of proteins that participates in post-translational modifications. One known SUMO target is the transcription factor nuclear factor-kB (NF-kB) that plays a pivotal role in many disease processes; sumoylation inactivates NF-kB by conjugation with inhibitors of NF-kB (IkB). Our laboratory demonstrated previously that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-kB, leading to nitrosative stress by the formation of peroxynitrite in the rostral ventrolateral medulla (RVLM), underpins the defunct brain stem cardiovascular regulation that precedes brain death. Based on an experimental endotoxemia model, this study evaluated the hypothesis that sumoylation plays a pro-life role in brain death by interacting with the NF-kB/NOS II/peroxynitrite signaling pathway in the RVLM. RESULTS: In Sprague-Dawley rats, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 10 mg kg-1) elicited an augmentation of SUMO-1 and ubiquitin-conjugase 9 (Ubc9) mRNA or protein levels, alongside SUMO-1-conjugated proteins in the RVLM. Immunoneutralization of SUMO-1 or Ubc9 in the RVLM significantly potentiated the already diminished sumoylation of IkBalpha and intensified NF-kB activation and NOS II/peroxynitrite expression in this brain stem substrate, together with exacerbated fatality, cardiovascular depression and reduction of an experimental index of a life-and-death signal detected from arterial pressure that disappears in comatose patients signifying failure of brain stem cardiovascular regulation before brain death. CONCLUSION: We conclude that sumoylation of IkB in the RVLM ameliorates the defunct brain stem cardiovascular regulation that underpins brain death in our experimental endotoxemia modal by reducing nitrosative stress via inhibition of IkB degradation that diminishes the induction of the NF-kB/NOS II/peroxynitrite signaling cascade. PMID- 27658614 TI - Wnt proteins can direct planar cell polarity in vertebrate ectoderm. AB - The coordinated orientation of cells across the tissue plane, known as planar cell polarity (PCP), is manifested by the segregation of core PCP proteins to different sides of the cell. Secreted Wnt ligands are involved in many PCP dependent processes, yet whether they act as polarity cues has been controversial. We show that in Xenopus early ectoderm, the Prickle3/Vangl2 complex was polarized to anterior cell edges and this polarity was disrupted by several Wnt antagonists. In midgastrula embryos, Wnt5a, Wnt11, and Wnt11b, but not Wnt3a, acted across many cell diameters to orient Prickle3/Vangl2 complexes away from their sources regardless of their positions relative to the body axis. The planar polarity of endogenous Vangl2 in the neuroectoderm was similarly redirected by an ectopic Wnt source and disrupted after depletion of Wnt11b in the presumptive posterior region of the embryo. These observations provide evidence for the instructive role of Wnt ligands in vertebrate PCP. PMID- 27658616 TI - Calcineurin inhibitor- and corticosteroid-free immunosuppression in pediatric heart transplant patients. AB - Pediatric heart transplant patients at our institution are immunosuppressed with a CNI and another immune-modulating agent without utilizing corticosteroids. Patients whose renal function worsened and who did not respond to CNI minimization had their CNI discontinued. The clinical history of 35 pediatric heart transplant patients with significant renal insufficiency whose CNI was discontinued was retrospectively analyzed. Data including serum creatinine and weight were collected before, at time of, and every 3-6 months after CNI discontinuation. This was used to calculate an eGFR. Cardiac allograft rejection and mortality data were also collected. CNI discontinuation occurred 39 times in 35 patients. The median eGFR significantly increased by 14 mL/min 3 months after CNI discontinuation and the increase continued to be significant (P<=.05) at 5 years. Freedom from rejection analysis showed no difference between graft rejection 2 years before versus after CNI discontinuation (P=.437). No mortality was associated with CNI discontinuation. Immunosuppression free of CNIs and corticosteroids appears to be a safe alternative in pediatric heart transplant patients with significant renal insufficiency. Furthermore, this strategy can significantly reverse renal insufficiency, even late after transplantation. PMID- 27658618 TI - Astaxanthin; a Promising Protector Against Gentamicin-Induced Nephrotoxicity in Rats. AB - Gentamicin is an aminoglycoside antibiotic widely used against infections caused by Gram-negative microorganisms. Nephrotoxicity is the main limitation to its therapeutic use. The objective of this study was to evaluate the potential protective effect of astaxanthin on the renal damage generated by gentamicin in rats, in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. The daily oral administration of the astaxanthin at a concentration of 50 mg/kg for 15 days to gentamicin (80 mg/kg.b.w) treated rats showed a significant decrease (p<0.05) in plasma creatinine, urea, TNF-alpha as well as plasma and renal MDA and HP. The treatment also resulted in a significant increase in hemoglobin, plasma sodium, potassium and TAS as well as renal total protein, GSH, Pr-SHs, G6PD, SOD, GPx, CAT and GR levels. The histological examinations of renal tissues in this study revealed damage and glomerular infiltration in gentamicin treated rats. The presented data suggest that astaxanthin has a significant prophylactic action against gentamicin induced nephrotoxicity in rats. The effect was more pronounced in case of astaxanthin pre-treatment compared with administration of astaxanthin post treatment. Taken together, astaxanthin has a potential as a protective and therapeutic agent for nephrotoxicity and deserves clinical trial in the near future as an adjuvant therapy in patients treated with gentamicin. PMID- 27658617 TI - Microglia contributes to plaque growth by cell death due to uptake of amyloid beta in the brain of Alzheimer's disease mouse model. AB - Pathological hallmarks of Alzheimer's disease (AD) include extracellularly accumulated amyloid beta (Abeta) plaques and intracellular neurofibrillary tangles in the brain. Activated microglia, brain-resident macrophages, are also found surrounding Abeta plaques. The study of the brain of AD mouse models revealed that Abeta plaque formation is completed by the consolidation of newly generated plaque clusters in vicinity of existed plaques. However, the dynamics of Abeta plaque formation, growth and the mechanisms by which microglia contribute to Abeta plaque formation are unknown. In the present study, we confirmed how microglia are involved in Abeta plaque formation and their growth in the brain of 5XFAD mice, the Abeta-overexpressing AD transgenic mouse model, and performed serial intravital two-photon microscopy (TPM) imaging of the brains of 5XFAD mice crossed with macrophage/microglia-specific GFP-expressing CX3CR1GFP/GFP mice. We found that activated microglia surrounding Abeta plaques take up Abeta, which are clusters developed inside activated microglia in vivo and this was followed by microglial cell death. These dying microglia release the accumulated Abeta into the extracellular space, which contributes to Abeta plaque growth. This process was confirmed by live TPM in vivo imaging and flow cytometry. These results suggest that activated microglia can contribute to formation and growth of Abeta plaques by causing microglial cell death in the brain. GLIA 2016;64:2274-2290. PMID- 27658619 TI - Novel and Neuroprotective Tetranortriterpenoids from Chinese Mangrove Xylocarpus granatum Koenig. AB - Eight new tetranortriterpenoids (1-8) were isolated from the twigs and leaves of the Chinese mangrove plant Xylocarpus granatum, together with four related known ones (9-12). The structures of new compounds were elucidated by detailed spectroscopic analysis. The absolute configuration of 9-epixylogranatin A (1) was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations of the solution conformers. Xylogranatumin A (2) represents the first example of the 9, 10-seco limonoid with an unprecedented oxygen-bridged B ring (2,7-dioxabicyclo[2.2.1]-heptane). All the isolates were evaluated for the in vitro neuroprotective activity, both compounds 11 and 12 displayed moderate effects against H2O2-induced neurotoxicity in PC12 cells at the concentration of 10 MUM, with an increase in cell viability of 12.0% and 11.6%, respectively. PMID- 27658620 TI - The effect of liquor licensing restrictions on assault: a quasi-experimental study in Sydney, Australia. AB - AIMS: To determine whether restrictions on the availability of alcohol in two inner-city entertainment areas in Sydney, Australia (1) reduced the incidence of assault in those areas, (2) increased the incidence of assault in nearby areas (where the restrictions did not apply), (3) resulted in a net reduction in overall levels of assault (4) and/or whether the reductions in assault were most pronounced during the daily time-periods when liquor trading restrictions were in operation. DESIGN: Structural time-series modelling was used to estimate and compare trends in assault in areas/times affected by the new restrictions on alcohol availability with trends in assault in areas unaffected by the new restrictions. SETTING: Sydney, Australia. PARTICIPANTS/MEASUREMENTS: The primary outcome measure was the police-recorded monthly incidence of non-domestic assault in the 78 months between January 2009 and June 2015. FINDINGS: Following the reforms, we found reductions in assaults of 45% [beta = -0.599, 95% confidence interval (CI) = -1.107, -0.091] and 22% (beta =0.260, 95% CI = -0.397, -0.123), respectively, in the Kings Cross and Sydney CBD Entertainment Precincts. In the Kings Cross Entertainment Precinct, reductions in assault were observed in all three daily time-periods. In the Sydney CBD Entertainment Precinct reductions in assault were observed only in the second and third daily time-periods. Assaults did not increase in entertainment areas adjacent to or within easy reach of the target areas. CONCLUSION: Restrictions on the availability of alcohol appear to reduce the incidence of assault. PMID- 27658621 TI - Genome sequencing and genetic characterization of Culex Flavirirus (CxFV) provides new information about its genotypes. AB - BACKGROUND: Culex Flavivirus (CxFV) is an insect-specific virus that is widely distributed and primarily infects mosquito species from the genus Culex. Its hosts include Culex tritaeniorhynchus, Culex quinquefasciatus, and Anopheles sinensis mosquitoes. Since its original identification, CxFV has been reported in several countries. Despite the increasing number of reports on CxFV, little is known about its genomic characteristics. It is unclear whether the phylogenetic relationships between the strains are influenced by host species and geographic location. RESULTS: We characterized the Brazilian CxFV strain and performed a comprehensive genetic and phylogenetic characterization of CxFV based on all ORF sequences described so far. Our results revealed that the Brazilian strain is in a monophyletic clade with the Mexican strain. Overall, selective pressure indicates that the ORF is undergoing purifying selection. CONCLUSIONS: The phylogenetic analysis revealed a strong association between climate and CxFV ancestry. Also, based on phylogeny and the genetic distance between the main branches of the tree, we propose the classification of the available sequences into two different genotypes. We also suggest the existence of two different subtypes within Genotype 1. PMID- 27658622 TI - Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity. AB - Synaptic plasticity often involves changes in the structure and composition of dendritic spines. Vesicular cargos and organelles enter spines either by exocytosing in the dendrite shaft and diffusing into spines or through a kinesin to myosin hand-off at the base of spines. Here we present evidence for microtubule (MT)-based targeting of a specific motor/cargo pair directly into hippocampal dendritic spines. During transient MT polymerization into spines, the kinesin KIF1A and an associated cargo, synaptotagmin-IV (syt-IV), are trafficked in unison along MTs into spines. This trafficking into selected spines is activity-dependent and results in exocytosis of syt-IV-containing vesicles in the spine head. Surprisingly, knockdown of KIF1A causes frequent fusion of syt-IV containing vesicles throughout the dendritic shaft and diffusion into spines. Taken together, these findings suggest a mechanism for targeting dendritic cargo directly into spines during synaptic plasticity and indicate that MT-bound kinesins prevent unregulated fusion by sequestering vesicular cargo to MTs. PMID- 27658624 TI - Oligomannan Prebiotic Attenuates Immunological, Clinical and Behavioral Symptoms in Mouse Model of Inflammatory Bowel Disease. AB - Inflammatory bowel disease shows increasing prevalence, however its pathomechanism and treatment is not fully resolved. Prebiotics are non-digestible carbohydrates which might provide an alternative to treat inflammatory conditions in the gut due to their positive effects either on the microbiome or through their direct effect on macrophages and mucosa. To test the protective effects of an oligomannan prebiotic, yeast cell wall mannooligosaccharide (MOS) was administered in dextran-sulphate-sodium (DSS)-induced mouse model of acute colitis. MOS reduced DSS-induced clinical- (weight loss, diarrhea) and histological scores (mucosal damage) as well as sickness-related anxiety. DSS treatment resulted in changes in colon microbiome with selective increase of Coliform bacteria. MOS administration attenuated colitis-related increase of Coliforms, normalized colonic muc2 expression and attenuated local expression of proinflammatory cytokines IL-1a, IL1b, IL6, KC, G-CSF and MCP1 as well as toll like receptor TLR4 and NLRP3 inflammasome. Some of the protective effects of MOS were likely be mediated directly through local macrophages because MOS dose dependently inhibited IL-1b and G-CSF induction following in vitro DSS challenge and IL1a, IL1b, G-SCF-, and IL6 increases after LPS treatment in mouse macrophage cell line RAW264.7. These results highlight oligomannan prebiotics as therapeutic functional food for testing in clinical trials. PMID- 27658625 TI - [Specific Learning Disabilities: Current challenges and opportunities]. PMID- 27658623 TI - Toll-Like Receptor 9 Activation Rescues Impaired Antibody Response in Needle-free Intradermal DNA Vaccination. AB - The delivery of plasmid DNA to the skin can target distinct subsets of dermal dendritic cells to confer a superior immune response. The needle-free immunization technology offers a reliable, safe and efficient means to administer intradermal (ID) injections. We report here that the ID injection of DNA vectors using an NF device (NF-ID) elicits a superior cell-mediated immune response, at much lesser DNA dosage, comparable in magnitude to the traditional intramuscular immunization. However, the humoral response is significantly impaired, possibly at the stage of B cell isotype switching. We found that the NF-ID administration deposits the DNA primarily on the epidermis resulting in a rapid loss of the DNA as well as the synthesized antigen due to the faster regeneration rate of the skin layers. Therefore, despite the immune-rich nature of the skin, the NF-ID immunization of DNA vectors may be limited by the impaired humoral response. Additional booster injections are required to augment the antibody response. As an alternative and a viable solution, we rescued the IgG response by coadministration of a Toll-like receptor 9 agonist, among other adjuvants examined. Our work has important implication for the optimization of the emerging needle-free technology for ID immunization. PMID- 27658626 TI - ? PMID- 27658627 TI - Response to "Trust, but verify" by Banaschewski et al. PMID- 27658628 TI - Check and Double Check - the Cochrane review by Storebo et al. (2015) is indeed flawed. PMID- 27658629 TI - ? PMID- 27658630 TI - ? PMID- 27658631 TI - ? PMID- 27658632 TI - Tumour metabolism: Metabolic flexibility. PMID- 27658633 TI - Genetics: Transcribing for the enemy. PMID- 27658634 TI - Tumour evolution: Evolving resistance in Tasmanian devils. PMID- 27658635 TI - Tumour metabolism: Functions of fumarate. PMID- 27658637 TI - Key clinical beam parameters for nanoparticle-mediated radiation dose amplification. AB - As nanoparticle solutions move towards human clinical trials in radiation therapy, the influence of key clinical beam parameters on therapeutic efficacy must be considered. In this study, we have investigated the clinical radiation therapy delivery variables that may significantly affect nanoparticle-mediated radiation dose amplification. We found a benefit for situations which increased the proportion of low energy photons in the incident beam. Most notably, "unflattened" photon beams from a clinical linear accelerator results in improved outcomes relative to conventional "flat" beams. This is measured by significant DNA damage, tumor growth suppression, and overall improvement in survival in a pancreatic tumor model. These results, obtained in a clinical setting, clearly demonstrate the influence and importance of radiation therapy parameters that will impact clinical radiation dose amplification with nanoparticles. PMID- 27658638 TI - The Healthy Infant Nasal Transcriptome: A Benchmark Study. AB - Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome wide transcriptomic analysis, and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates, and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently, and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology, and describes normal gene expression and variation within a healthy infant cohort. PMID- 27658639 TI - 3D-Printed Zeolite Monoliths for CO2 Removal from Enclosed Environments. AB - Structured adsorbents, especially in the form of monolithic contactors, offer an excellent gas-solid contacting strategy for the development of practical and scalable CO2 capture technologies. In this study, the fabrication of three dimensional (3D)-printed 13X and 5A zeolite monoliths with novel structures and their use in CO2 removal from air are reported. The physical and structural properties of these printed monoliths are evaluated and compared with their powder counterparts. Our results indicate that 3D-printed monoliths with zeolite loadings as high as 90 wt % exhibit adsorption uptake that is comparable to that of powder sorbents. The adsorption capacities of 5A and 13X monoliths were found to be 1.59 and 1.60 mmol/g, respectively, using 5000 ppm (0.5%) CO2 in nitrogen at room temperature. The dynamic CO2/N2 breakthrough experiments show relatively fast dynamics for monolithic structures. In addition, the printed zeolite monoliths show reasonably good mechanical stability that can eventually prevent attrition and dusting issues commonly encountered in traditional pellets and beads packing systems. The 3D printing technique offers an alternative, cost effective, and facile approach to fabricate structured adsorbents with tunable structural, chemical, and mechanical properties for use in gas separation processes. PMID- 27658636 TI - Oxygen availability and metabolic adaptations. AB - Oxygen availability, along with the abundance of nutrients (such as glucose, glutamine, lipids and albumin), fluctuates significantly during tumour evolution and the recruitment of blood vessels, leukocytes and reactive fibroblasts to complex tumour microenvironments. As such, hypoxia and concomitant nutrient scarcity affect large gene expression programmes, signalling pathways, diverse metabolic reactions and various stress responses. This Review summarizes our current understanding of how these adaptations are integrated in hypoxic tumour cells and their role in disease progression. PMID- 27658641 TI - On second harmonic generation and multiphoton-absorption induced luminescence from laser-reshaped silver nanoparticles embedded in glass. AB - Spherical silver nanoparticles (NPs) of 30 nm diameter embedded in soda-lime glass were uniformly reshaped (elongated) after irradiation by a linearly polarised 250 fs pulsed laser operating within the NPs' surface plasmon resonance band. We observed second harmonic generation (SHG) and multiphoton-absorption induced luminescence (MAIL) in the embedded laser-reshaped NPs upon picosecond (10 ps) pulsed laser excitation at 1064 nm. A complementary study of SHG and MAIL was conducted in soda-lime glass containing embedded, mechanically-reshaped silver NPs of a similar elongation ratio (aspect ratio) to the laser-reshaped NPs. This supports the notion that the observed difference in SHG and MAIL in the studied nanocomposite systems is due to the shape modification mechanism. The discrete dipole approximation method was used to assess the absorption and scattering cross-sections of the reshaped NPs with different elongation ratios. PMID- 27658640 TI - 24 hours stay after hip replacement. AB - Background and purpose - The length of stay after total hip arthroplasty has been reduced to 2-4 days after implementing fast-track surgery. We investigated whether a new time-based patient-centered primary direct anterior approach (DAA) total hip arthroplasty (THA) treatment protocol in a specialized clinic, with a planned length of stay of about 24 hours, could be achieved in all patients or only in a selected group of patients. Patients and methods - We analyzed prospectively collected data in a cohort of 378 consecutive patients who underwent a primary direct anterior THA as a patient-centered time-based procedure between March 1, 2012 and December 31, 2015. Patients with complicated medical comorbidity and those over the age of 85 were excluded from the study. The average length of stay was recorded and all complications, re-admissions, and reoperations were registered and analyzed. The primary outcome measures were length of stay and complication rate, at discharge and 90 days postoperatively. Results - The average length of stay for all patients was 26 hours. All patients were discharged from the clinic on the day after the operation and were able to continue their recovery at home or in a rehabilitation facility. The overall complication rate within 3 months of surgery was 6%. The 3-month re-admission rate and the 3-month reoperation rate were both 2%. Interpretation - Performing a time-based, patient-centered fast-track program for DAA total hip arthroplasty can result in a standardized length of stay of about 24 hours and a high level of patient satisfaction with few complications, re-admissions, and reoperations. PMID- 27658642 TI - PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma. AB - Aberrant activation of PI3K-AKT signaling in many pathological conditions including cancer has attracted much of interest for drug targeting. Various isoforms are known from three classes of PI3K. Targeting selective isoform is advantageous to overcome the global deleterious effects of drug. PI-103 is a specific inhibitor of p110alpha of class I PI3K. The present study is aimed to analyze anti-carcinogenic activity of PI-103 in Dalton's lymphoma ascite (DLA) cells. Result shows regression in cell proliferation and increased apoptosis in terms of increased Annexin V binding, nuclear fragmentation and active caspase 3 level. It is correlated with attenuation of PI3K-AKT signaling by PI-103 via downregulation of the level of p110alpha, phospho-p85alpha, phospho- AKT, and PKCalpha in DLA cells as well as in H2O2 induced DLA cells. Additionally, ROS accumulation is declined in H2O2 induced DLA cells. Overall result suggests that PI-103 attenuates PI3K-AKT signaling via induction of apoptosis in murine T-cell lymphoma. PMID- 27658643 TI - The analgesic action of desmopressin in renal colic. AB - Urolithiasis is a frequent problem causing a significant clinical, psychological and socio-economic burden. Analgesia remains the most important element in the medical treatment of renal colic. Nonetheless, both NSAIDs and opiates have a side effect profile which can cause further complications. As such, the use of desmopressin for renal colic has received increased attention in the last two decades. This paper provides an overview of current evidence on the use of desmopressin as an analgesic strategy in renal colic. PMID- 27658644 TI - Direct identification of microorganisms from positive blood cultures by MALDI-TOF MS using an in-house saponin method. AB - OBJECTIVES: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a fast and reliable method for the identification of bacteria. A MALDI Sepsityper kit is generally used to prepare samples obtained directly from culture bottles. However, the relatively high cost of this kit is a major obstacle to introducing this method into routine clinical use. In this study, the accuracies of three different preparation methods for rapid direct identification of bacteria from positive blood culture bottles by MALDI-TOF MS analysis were compared. METHODS: In total, 195 positive bottles were included in this study. RESULTS: Overall, 78.5%, 68.7%, and 76.4% of bacteria were correctly identified to the genus level (score >=1.7) directly from positive blood cultures using the Sepsityper, centrifugation, and saponin methods, respectively. The identification rates using the Sepsityper and saponin methods were significantly higher than that using the centrifugation method (Sepsityper vs. centrifugation, p<0.001; saponin vs. centrifugation, p=0.003). CONCLUSIONS: These results suggest that the saponin method is superior to the centrifugation method and comparable to the Sepsityper method in the accuracy of rapid bacterial identification directly from blood culture bottles, and could be a less expensive alternative to the Sepsityper method. PMID- 27658646 TI - A new patchoulane-type sesquiterpenoid glycoside from the roots of Croton crassifolius. AB - A new patchoulane-type sesquiterpenoid glycoside (1), together with five known sesquiterpenoids (2-6), was isolated from the roots of Croton crassifolius. Their structures were elucidated on the basis of spectroscopic methods. This is the first report about the sesquiterpenoid glycoside from C. crassifolius. All the isolated compounds 1-6 were evaluated for their cytotoxic activities against human tumour cell lines HL-60 and A549, but none showed significant activity. PMID- 27658645 TI - Salivirus in children with diarrhoea, western India. PMID- 27658647 TI - Calcitonin-Negative Neuroendocrine Tumor of the Thyroid. AB - Neuroendocrine tumors (NETs) of the thyroid are rare; the most common type is medullary thyroid carcinoma (MTC). They are derived from parafollicular cells (C cells) that usually express calcitonin, chromogranin, and carcinoembryonic antigen. Calcitonin-negative NETs of the thyroid are extremely rare, and the origin of these tumors is unclear. Whereas some believe that these tumors are from follicular cells, recent reports have shown expression of calcitonin gene related peptide in these tumors, indicating parafollicular C-cell origin. Here, we report a case of calcitonin-negative NET of the thyroid in a 74-year-old woman, with review of the literature. PMID- 27658649 TI - Ethiopia's health extension workers use of work time on duty: time and motion study. AB - Ethiopia implemented an innovative community-based health program, called the health extension program, to enhance access to basic health promotion, disease prevention and selected curative services by establishing health posts in every village, also called kebeles, with average of 5000 people, staffed with two health extension workers (HEWs). This time and motion study was done to estimate the amount of time that HEWs spend on various work duties and to explore differences in urban compared with rural settings and among regions. A total of 44 HEWs were observed for 21 consecutive days, and time and motion data were collected using tablet computers. On average, HEWs were on duty for 15.5 days out of the 21 days of observation period, and on average, they stayed on duty for about 6 hours per day. Out of the total observed work time, the percentages of total time spent on various activities were as follows: providing health education or services (12.8%); participating in meetings and giving trainings (9.3%); conducting community mapping and mobilization (0.8%); recordkeeping, reporting, managing family folders (13.2%); managing commodities and supplies (1.3%); receiving supervision (3.2%); receiving training (1.6%); travel between work activities (15.5%); waiting for clients in the health post (or health centre in urban settings) (24.9%); building relationships in the community (13.3%); and other activities that could not be meaningfully categorized (4%). The proportion of time spent on different activities and the total time worked varied significantly between rural and urban areas and among the regions (at P < 0.05). Findings of this study indicate that only a minority of HEW time is spent on providing health education and services, and substantial time is spent waiting for clients. The efficiency of the HEW model may be improved by creating more demand for services or by redesigning service delivery modalities. PMID- 27658650 TI - Recreational physical activity in natural environments and implications for health: A population based cross-sectional study in England. AB - BACKGROUND: Building on evidence that natural environments (e.g. parks, woodlands, beaches) are key locations for physical activity, we estimated the total annual amount of adult recreational physical activity in England's natural environments, and assessed implications for population health. METHODS: A cross sectional analysis of six waves (2009/10-2014/5) of the nationally representative, Monitor of Engagement with the Natural Environment survey (n=280,790). The survey uses a weekly quota sample, and population weights, to estimate nature visit frequency across England, and provides details on a single, randomly selected visit (n=112,422), including: a) duration; b) activity; and c) environment type. RESULTS: Approximately 8.23 million (95% CIs: 7.93, 8.54) adults (19.5% of the population) made at least one 'active visit' (i.e. >=30min, >=3 METs) to natural environments in the previous week, resulting in 1.23 billion (1.14, 1.32) 'active visits' annually. An estimated 3.20 million (3.05, 3.35) of these also reported meeting recommended physical activity guidelines (i.e. >=5*30min a week) fully, or in part, through such visits. Active visits by this group were associated with an estimated 109,164 (101,736, 116,592) Quality Adjusted Life Years (QALYs) annually. Assuming the social value of a QALY to be L20,000, the annual value of these visits was approximately L2.18 billion (L2.03, L2.33). Results for walking were replicated using WHO's Health Economic Assessment Tool. CONCLUSIONS: Natural environments provide the context for a large proportion of England's recreational physical activity and highlight the need to protect and manage such environments for health purposes. PMID- 27658648 TI - High butter-fat diet and bisphenol A additively impair male rat spermatogenesis. AB - Exposure to xenoestrogens is a probable cause of male infertility in humans. Consumption of high-fat diets and exposure to bisphenol A (BPA) is pervasive in America. Here, we test the hypothesis that gestational exposure to high dietary fats and/or BPA disrupt spermatogenesis in adulthood. Sprague-Dawley rats were fed diets containing 10kcal% butter fat (AIN), 39kcal% butter fat (HFB), or 39kcal% olive oil (HFO), with or without BPA (25MUg/kg body weight/day) during pregnancy. One group of male offspring received testosterone (T)- and estradiol 17beta (E2)-filled implants or sham-implants from postnatal day (PND)70-210. Another group was naturally aged to 18 months. We found that adult males with gestational exposure to BPA, HFB, or HFB+BPA, in both the aged group and the T+E2 implanted group, exhibited impairment of spermatogenesis. In contrast, gestational exposure to HFO or HFO+BPA did not affect spermatogenesis. Sham implanted, gestational exposed groups also had normal spermatogenesis. Loss of ERalpha expression in round spermatids and premature expression of protamine-1 in diplotene spermatocytes were features associated with impaired spermatogenesis. Compared with the single-treatment groups, the HFB+BPA group experienced more severe effects, including atrophy. PMID- 27658651 TI - A novel protocol for dispatcher assisted CPR improves CPR quality and motivation among rescuers-A randomized controlled simulation study. AB - BACKGROUND: Emergency dispatchers use protocols to instruct bystanders in cardiopulmonary resuscitation (CPR). Studies changing one element in the dispatcher's protocol report improved CPR quality. Whether several changes interact is unknown and the effect of combining multiple changes previously reported to improve CPR quality into one protocol remains to be investigated. We hypothesize that a novel dispatch protocol, combining multiple beneficial elements improves CPR quality compared with a standard protocol. METHODS: A novel dispatch protocol was designed including wording on chest compressions, using a metronome, regular encouragements and a 10-s rest each minute. In a simulated cardiac arrest scenario, laypersons were randomized to perform single-rescuer CPR guided with the novel or the standard protocol. PRIMARY OUTCOME: a composite endpoint of time to first compression, hand position, compression depth and rate and hands-off time (maximum score: 22 points). Afterwards participants answered a questionnaire evaluating the dispatcher assistance. RESULTS: The novel protocol (n=61) improved CPR quality score compared with the standard protocol (n=64) (mean (SD): 18.6 (1.4)) points vs. 17.5 (1.7) points, p<0.001. The novel protocol resulted in deeper chest compressions (mean (SD): 58 (12)mm vs. 52 (13)mm, p=0.02) and improved rate of correct hand position (61% vs. 36%, p=0.01) compared with the standard protocol. In both protocols hands-off time was short. The novel protocol improved motivation among rescuers compared with the standard protocol (p=0.002). CONCLUSIONS: Participants guided with a standard dispatch protocol performed high quality CPR. A novel bundle of care protocol improved CPR quality score and motivation among rescuers. PMID- 27658652 TI - Recognition of out-of-hospital cardiac arrest by medical dispatchers in emergency medical dispatch centres in two countries. AB - INTRODUCTION: Survival after out-of-hospital cardiac arrest (OHCA) remains low. Early recognition by emergency medical dispatchers is essential for an effective chain of actions, leading to early cardiopulmonary resuscitation, use of an automated external defibrillator and rapid dispatching of the emergency medical services. AIM: To analyse and compare the accuracy of OHCA recognition by medical dispatchers in two countries. METHOD: An observational register-based study collecting data from national cardiac arrest registers in Denmark and Sweden during a six-month period in 2013. Data were analysed in two steps; registry data were merged with electronically registered emergency call data from the emergency medical dispatch centres in the two regions. Cases with missing or non-OHCA dispatch codes were analysed further by auditing emergency call recordings using a uniform data collection template. RESULTS: The sensitivity for recognition of OHCA was 40.9% (95% CI: 37.1-44.7%) in the Capital Region of Denmark and 78.4% (95% CI: 73.2-83.0%) in the Skane Region in Sweden (p<0.001). With additional data from the emergency call recordings, the sensitivity was 80.7% (95% CI: 77.7 84.3%) and 86.0% (95% CI: 81.3-89.8%) for the two regions (p=0.06). The majority of the non-recognised OHCA were dispatched with the highest priority. CONCLUSION: The accuracy of OHCA recognition was high and comparable. We identified large differences in data registration practices despite the use of similar dispatch tools. This raises a discussion of definitions and transparency in general in scientific reporting of OHCA recognition, which is essential if used as quality indicator in emergency medical services. PMID- 27658653 TI - Dynamic prediction of patient outcomes during ongoing cardiopulmonary resuscitation. AB - PURPOSE: The probability of the return of spontaneous circulation (ROSC) and subsequent favourable outcomes changes dynamically during advanced cardiac life support (ACLS). We sought to model these changes using time-to-event analysis in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Adult (>=18 years old), non-traumatic OHCA patients without prehospital ROSC were included. Utstein variables and initial arterial blood gas measurements were used as predictors. The incidence rate of ROSC during the first 30min of ACLS in the emergency department (ED) was modelled using spline-based parametric survival analysis. Conditional probabilities of subsequent outcomes after ROSC (1-week and 1-month survival and 6-month neurologic recovery) were modelled using multivariable logistic regression. The ROSC and conditional probability models were then combined to estimate the likelihood of achieving ROSC and subsequent outcomes by providing k additional minutes of effort. RESULTS: A total of 727 patients were analyzed. The incidence rate of ROSC increased rapidly until the 10th minute of ED ACLS, and it subsequently decreased. The conditional probabilities of subsequent outcomes after ROSC were also dependent on the duration of resuscitation with odds ratios for 1-week and 1-month survival and neurologic recovery of 0.93 (95% CI: 0.90-0.96, p<0.001), 0.93 (0.88-0.97, p=0.001) and 0.93 (0.87-0.99, p=0.031) per 1-min increase, respectively. Calibration testing of the combined models showed good correlation between mean predicted probability and actual prevalence. CONCLUSIONS: The probability of ROSC and favourable subsequent outcomes changed according to a multiphasic pattern over the first 30min of ACLS, and modelling of the dynamic changes was feasible. PMID- 27658654 TI - The impact of hospital experience with out-of-hospital cardiac arrest patients on post cardiac arrest care. AB - OBJECTIVE: Patient volume as a surrogate for institutional experience has been associated with quality of care indicators for a variety of illnesses. We evaluated the association between hospital experience with comatose out-of hospital cardiac arrest (OHCA) patients and important care processes. METHODS: This was a population-based, retrospective cohort study using data from 37 hospitals in Southern Ontario from 2007 to 2013. We included adults with atraumatic OHCA who were comatose on emergency department arrival and survived at least 6h. We excluded patients with a Do-Not-Resuscitate order or severe bleeding within 6h of hospital arrival. Multi-level logistic regression models estimated the association between average annual hospital volume of OHCA patients and outcomes. The primary outcome was successful targeted temperature management (TTM) and secondary outcomes included TTM initiation, premature withdrawal of life-sustaining therapy, and survival with good neurologic function. RESULTS: Our analysis included 2723 patients. For every increase of 10 in the average annual volume of eligible patients, the adjusted odds increased by 30% for successful TTM (OR 1.29, 95% CI 1.03-1.62) and by 38% for initiating TTM (OR 1.38, 95% CI 1.11-1.72). No significant association between patient volume and other secondary outcomes was observed. CONCLUSIONS: Patients arriving at hospitals with more experience treating comatose post cardiac arrest patients are more likely to have TTM initiated and to successfully reach target temperature. Our findings have implications for regional systems of care and knowledge translation efforts aiming to improve quality of care for this patient population. PMID- 27658655 TI - Co-location of passive gear fisheries in offshore wind farms in the German EEZ of the North Sea: A first socio-economic scoping. AB - Worldwide the renewable energy sector is expanding at sea to address increasing demands. Recently the race for space in heavily used areas such as the North Sea triggered the proposal of co-locating other activities such as aquaculture or fisheries with passive gears in offshore wind farms (OWFs). Our interdisciplinary approach combined a quantification of spatial overlap of activities by using Vessel Monitoring System and logbook data with a stakeholder consultation to conclude and verify on the actual feasibility of co-location. In the German Exclusive Economic Zone (EEZ) of the North Sea up to 90% of Danish and 40% of German annual gillnet fleet landings of plaice overlapped with areas where OWFs are developed. Our results indicated further that the international gillnet fishery could lose up to 50% in landings within the North Sea German EEZ when OWF areas are closed entirely for fisheries. No spatial overlap was found for UK potters targeting brown crab in the German EEZ. We further identified a number of key issues and obstacles that to date hinder an actual implementation of co location as a measure in the marine spatial planning process: defining the legal base; implementation of safety regulations; delineation of minimum requirements for fishing vessels such as capacities, quotas, technical equipment; implementation of a licensing process; and scoping for financial subsidies to set up business. The stakeholder consultation verified the scientific findings and highlighted that all those points need to be addressed in a planning process. In the German EEZ we have shown that the socio-economic importance of spatial overlap varies within planning boundaries. Therefore we recommend an interdisciplinary bottom-up approach when scoping for suitable areas of co location. Hence, an informed marine spatial planning process requires comprehensive and spatial explicit socio-economic viability studies factoring in also ecological effects of OWFs on target species. PMID- 27658656 TI - An environmental analysis of options for utilising wasted food and food residue. AB - The potential environmental impact of wasted food minimisation versus its utilisation in a circular bioeconomy is investigated based on a case study of Ireland. The amount of wasted food and food residue (WFFR) produced in 2010 was used for business-as-usual, (a) and four management options were assessed, (b) minimisation, (c) composting, (d) anaerobic digestion and (e) incineration. The environmental impacts Global Warming Potential (GWP), Acidification Potential (AP) and Eutrophication Potential (EP) were considered. A carbon return on investment (CRoI) was calculated for the three processing technologies (c-e). The results showed that a minimisation strategy for wasted food would result in the greatest reduction of all three impacts, -4.5 Mt CO2-e (GWP), -11.4 kt PO43-e (EP) and -43.9 kt SO2-e (AP) compared to business as usual. For WFFR utilisation in the circular bioeconomy, anaerobic digestion resulted in the lowest environmental impact and best CRoI of -0.84 kg CO2-e per Euro. From an economic perspective, for minimisation to be beneficial, 0.15 kg of wasted food would need to be reduced per Euro spent. PMID- 27658657 TI - Irrigated greywater in an urban sub-division as a potential source of metals to soil, groundwater and surface water. AB - Increased water demands in dry countries such as Australia, have led to increased adoption of various water reuse practices. Irrigation of greywater (all water discharged from the bathrooms, laundry and kitchen apart from toilet waste) is seen as a potential means of easing water demands; however, there is limited knowledge of how greywater irrigation impacts terrestrial and aquatic environments. This study compared four greywater irrigated residential lots to adjacent non-irrigated lots that acted as controls. Accumulation and potential impacts of metals in soil, groundwater and surface water, as a result of greywater irrigation, were assessed by comparing measured concentrations to national and international guidelines. Greywater increased concentrations of some metals in irrigated soil and resulted in As, B, Cr and Cu exceeding guidelines after only four years of irrigation. Movement of metals from the irrigation areas resulted in metal concentrations in groundwater (Al, As, Cr, Cu, Fe, Mn, Ni and Zn) and surface water (Cu, Fe and Zn) exceeding environmental quality guidelines again within four years. These results are unlikely to be universally applicable but indicate the need to consider metals in greywater in order to minimize potential adverse environmental effects from greywater irrigation. PMID- 27658658 TI - Modelling and experimental checking of the influence of substrate concentration on the first order kinetic constant in photo-processes. AB - Most photoprocesses follow a pseudo first order kinetic law and, commonly, the kinetic parameter depends on the initial concentration of the substrate. In this work, a kinetic model, which explains this dependence on the substrate concentration and on the other operational variables, has been developed. In the model, mass transfer of substrate from the bulk solution to the wall of the photoreactor was assumed as the step determining the rate of the process. To check the model, methylene blue (MB) has been used as model substrate and photodegradation experiments have been carried out in an exciplex KrCl flow through photoreactor, It was observed that the methylene blue conversion improved with a decrease in its initial concentration, in good agreement with the model. Also, by fitting the experimental data to the model, high correlation coefficients and a high degree of agreement between experimental and calculated conversion was obtained, which validates the model. PMID- 27658659 TI - Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals. AB - OBJECTIVE: The formation of reactive oxygen species (ROS) contributes to the pathogenesis and progression of several diseases. Polyphenols have been shown to be beneficial against ROS. The aim of this study was to evaluate the effects of a natural antioxidant ice cream on oxidative stress, vascular function, and physical performance. METHODS: In this controlled, single-blind, crossover study, 14 healthy individuals were randomized to consume 100 g of either antioxidant ice cream containing dark cocoa powder and hazelnut and green tea extracts or milk chocolate ice cream (control ice cream). Participants were studied at baseline and 2 h after ingesting ice cream. Serum polyphenols, antioxidant status (ferric reducing ability of plasma [FRAP]), nitric oxide (NOx) bioavailability, markers of oxidative stress (determination of reactive oxygen metabolites [d-ROMs] and hydrogen peroxide [H2O2]), endothelium function (flow-mediated dilation [FMD] and reactive hyperemia index [RHI]), and exercise tolerance (stress test) were assessed, and the double product was measured. RESULTS: Serum polyphenols (P < 0.001), NOx (P < 0.001), FRAP (P < 0.005), FMD (P < 0.001), and RHI (P < 0.05) increased significantly, oxidative stress decreased (d-Roms, P < 0.001; H2O2, P < 0.001), and the double product (P < 0.001) was improved only after antioxidant ice cream ingestion. No changes were found after control ice cream ingestion. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that a natural ice cream rich in polyphenols acutely improved vascular function and physical performance in healthy individuals through a reduction in oxidative stress. PMID- 27658660 TI - eHealth literacy in chronic disease patients: An item response theory analysis of the eHealth literacy scale (eHEALS). AB - BACKGROUND: Chronic disease patients are affected by low computer and health literacy, which negatively affects their ability to benefit from access to online health information. OBJECTIVE: To estimate reliability and confirm model specifications for eHealth Literacy Scale (eHEALS) scores among chronic disease patients using Classical Test (CTT) and Item Response Theory techniques. METHODS: A stratified sample of Black/African American (N=341) and Caucasian (N=343) adults with chronic disease completed an online survey including the eHEALS. Item discrimination was explored using bi-variate correlations and Cronbach's alpha for internal consistency. A categorical confirmatory factor analysis tested a one factor structure of eHEALS scores. Item characteristic curves, in-fit/outfit statistics, omega coefficient, and item reliability and separation estimates were computed. RESULTS: A 1-factor structure of eHEALS was confirmed by statistically significant standardized item loadings, acceptable model fit indices (CFI/TLI>0.90), and 70% variance explained by the model. Item response categories increased with higher theta levels, and there was evidence of acceptable reliability (omega=0.94; item reliability=89; item separation=8.54). CONCLUSION: eHEALS scores are a valid and reliable measure of self-reported eHealth literacy among Internet-using chronic disease patients. PRACTICE IMPLICATIONS: Providers can use eHEALS to help identify patients' eHealth literacy skills. PMID- 27658662 TI - A Nationwide Assessment of the Emergency Department Management of Acute Urinary Retention Due to Urethral Stricture. AB - OBJECTIVE: To evaluate the nationwide practice patterns of the management of acute urinary retention (AUR) secondary to urethral stricture (US) in an emergency department (ED) setting. MATERIALS AND METHODS: We used the 2006-2010 Nationwide Emergency Department Sample to identify men with US who received treatment for AUR. We excluded patients with benign prostatic hyperplasia, vesicourethral anastomotic stenosis, neurogenic bladder, and bladder cancer. Primary outcome was urethral dilation or suprapubic tube (SPT) placement as initial AUR management. Patient demographics and hospital factors were also examined. Multivariate logistic regression was performed to examine factors associated with initial AUR management. RESULTS: We identified 4794 weighted ED encounters of men with US who underwent urethral dilation or SPT placement for AUR. Mean age was 58.6 +/- 0.8 years. A total of 4084 (85%) men received urethral dilation, whereas 710 had SPT (15%) placement. In bivariate analysis, patients who received SPT were likely to be younger (P <.001), treated in recent years (P = .002), and in hospitals in the West region (P = .003). In multivariate analysis, SPT placement was significantly associated with younger age (P = .004), public insurance (P = .03), recent treatment years (P = .02), and hospitals in the West region (P = .02). Income and hospital teaching status did not have significant association with initial treatment choice. CONCLUSION: Urethral dilation remains the most common urologic intervention in the ED for AUR due to US; however, there is an increasing trend toward SPT placement. Patients who are younger, publicly insured, or who receive care in the West region are more likely to receive a SPT for initial treatment of AUR due to US. PMID- 27658661 TI - Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study. AB - OBJECTIVE: To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. METHODS: A randomized, double blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded. RESULTS: Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits. PMID- 27658664 TI - Role of compression therapy in pathophysiology of the venous system in lower limbs. AB - The management of varicose veins and their sequelae are estimated to cost the NHS approximately L400-600 m annually. Along with interventional procedures, the National Institute for Health and Care Excellence (NICE) also recommends the use of compression therapy. With the vast array of different compression therapies available, prescribing the correct method can be challenging, with patients receiving incorrect compression being a matter of concern. This review summarises the key principles underpinning the management of these patients with particular emphasis on the pathophysiology and different classes of compression. PMID- 27658663 TI - Management of Duodenal Involvement During Retroperitoneal Lymph Node Dissection for Germ Cell Tumors. AB - OBJECTIVE: To describe patient characteristics and outcomes after duodenal repair during postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and to identify treatment and management patterns. METHODS: The Indiana University Testis Cancer database was used to identify all patients who underwent simultaneous partial duodenectomy and PC-RPLND from 1983 to 2013. Patient records were reviewed to describe patient and tumor characteristics, type of duodenal restoration, postoperative management, and complications. RESULTS: Of the 2223 PC RPLND performed during the study period, we identified 39 patients who underwent simultaneous duodenectomy, with 1 patient requiring 2 duodenal procedures for a total of 40 duodenal procedures. The postchemotherapy median tumor mass size was 8.95 (2.5-17) cm. Fifty percent of cases were standard PC-RPLND; the remainders were redo, desperation, or late relapse cases. Preoperative gastrointestinal symptoms were present in 21% of patients and included bowel obstruction (8%) or gastrointestinal bleeding (13%). Retroperitoneal pathology consisted of teratoma (48%), cancer (33%), and necrosis (20%). Duodenal involvement was managed with primary duodenorrhaphy (68%), duodenojejunostomy (18%), duodenoduodenostomy (13%), or pancreaticoduodenectomy (3%). Starting in the year 2000, duodenostomy and gastrostomy tubes were no longer used. The most common postoperative complication was ileus (45%) with a 3% duodenal fistula rate. CONCLUSION: Duodenal tumor involvement during PC-RPLND is most commonly managed with primary duodenorrhaphy after partial duodenectomy with an acceptable duodenal fistula rate. The routine use of duodenostomy or gastrostomy tubes is not recommended. PMID- 27658665 TI - Cognitive training: How can it be adapted for surgical education? AB - BACKGROUND: There is a need for new approaches to surgical training in order to cope with the increasing time pressures, ethical constraints, and legal limitations being placed on trainees. One of the most interesting of these new approaches is "cognitive training" or the use of psychological processes to enhance performance of skilled behaviour. Its ability to effectively improve motor skills in sport has raised the question as to whether it could also be used to improve surgical performance. The aim of this review is to provide an overview of the current evidence on the use of cognitive training within surgery, and evaluate the potential role it can play in surgical education. METHODS: Scientific database searches were conducted to identify studies that investigated the use of cognitive training in surgery. The key studies were selected and grouped according to the type of cognitive training they examined. RESULTS: Available research demonstrated that cognitive training interventions resulted in greater performance benefits when compared to control training. In particular, cognitive training was found to improve surgical motor skills, as well as a number of non-technical outcomes. Unfortunately, key limitations restricting the generalizability of these findings include small sample size and conceptual issues arising from differing definitions of the term 'cognitive training'. CONCLUSIONS: When used appropriately, cognitive training can be a highly effective supplementary training tool in the development of technical skills in surgery. Although further studies are needed to refine our understanding, cognitive training should certainly play an important role in future surgical education. PMID- 27658667 TI - There are too many medical physics journals! PMID- 27658666 TI - Point-of-care universal screening for meticillin-resistant Staphylococcus aureus: a cluster-randomized cross-over trial. AB - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is frequently endemic in healthcare settings and may be transmitted by person-to-person spread. Asymptomatic MRSA carriers are potential, unsuspected sources for transmission and some of them may be identified by admission screening. AIM: To assess whether rapid point-of-care screening (POCS) for MRSA at hospital admission may be associated with a reduction in MRSA acquisition rates when compared with slower laboratory-based methods. METHODS: A cluster-randomized cross-over trial was conducted in four admission wards of an acute London tertiary care hospital. Polymerase chain reaction-based POCS screening was compared with conventional culture screening. Patients were screened on ward admission and discharge, and the MRSA acquisition rate on the admission wards was calculated as the primary outcome measure. RESULTS: In all, 10,017 patients were included; 4978 in the control arm, 5039 in the POCS arm. The MRSA carriage rate on admission was 1.7%. POCS reduced the median reporting time from 40.4 to 3.7 h (P < 0.001). MRSA was acquired on the admission wards by 23 (0.46%) patients in the control arm and by 24 (0.48%) in the intervention arm, acquisition rates of 5.39 and 4.60 per 1000 days respectively. After taking account of predefined confounding factors, the adjusted incidence rate ratio (IRR) for change in trend for MRSA acquisition was 0.961 (95% confidence interval: 0.766-1.206). The adjusted IRR for step change for MRSA acquisition was 0.98 (0.304-3.162). CONCLUSION: POCS produces a significantly faster result but has no effect on MRSA acquisition on admission wards compared with culture screening. Where compliance with infection prevention and control is high and MRSA carriage is low, POCS has no additional impact on MRSA acquisition rates over the first one to four days of admission compared with conventional culture screening. PMID- 27658668 TI - The ups and downs of low dose ionising radiobiology research. PMID- 27658670 TI - National Survey of State Children's Mental Health Directors: Current Status and Future Directions. AB - State agencies play a critical role in addressing the mental health needs of children and youth. Significant changes underway throughout the nation at the federal and state levels have led to questions about the role of state children's mental health (CMH) agencies and the effects of these changes on children's services. The purpose of this study was to examine the current status of state offices for CMH with regard to structure and responsibilities and to identify what state CMH directors express as opportunities and challenges for CMH at the state level. CMH directors or their representatives from 46 states, 1 US territory, and D.C. completed an online survey developed to address the specific aims of this study. Findings highlight the importance of a strong state structure to support CMH and opportunities for reform and system change, particularly related to the Affordable Care Act and expansion of Systems of Care. PMID- 27658669 TI - Differences in the association between childhood trauma history and borderline personality disorder or attention deficit/hyperactivity disorder diagnoses in adulthood. AB - Common environmental etiological factors between borderline personality disorder (BPD) and attention deficit/hyperactivity disorder (ADHD) have not been fully studied. The main aim of this study was to investigate the relationship between childhood trauma histories, assessed by the Childhood Trauma Questionnaire-Short Form (CTQ-SF), with adult BPD, ADHD or BPD-ADHD diagnoses. Comorbid BPD-ADHD patients exhibited significantly higher clinical severity and higher scores in the Total Neglect Scale, compared to BPD and ADHD patients, and only a marginal difference was observed for Sexual Abuse when BPD and ADHD patients were compared. Physical Trauma Scales were associated with ADHD diagnosis, whereas Emotional Abuse and Sexual Abuse Scales were associated with BPD or BPD-ADHD diagnoses. The study findings support the association between experiencing traumatic events in childhood and a higher clinical severity of BPD in adulthood. Furthermore, physical trauma history in childhood could be associated with the persistence of ADHD in adulthood and emotional or sexual abuse with later development of BPD or comorbid BPD-ADHD. Whereas experiencing childhood traumas is associated with later development of more general psychopathology, our study supports that a specific type of traumatic event could increase the risk for the consolidation of a concrete psychiatric disorder in the trajectory from childhood to adulthood of vulnerable subjects. PMID- 27658671 TI - Residential Moves Among Housing First Participants. PMID- 27658672 TI - The prevalence of heat-related cardiorespiratory symptoms: the vulnerable groups identified from the National FINRISK 2007 Study. AB - The prevalence of heat-related cardiorespiratory symptoms among vulnerable groups is not well known. We therefore estimated the prevalence of heat-related cardiorespiratory symptoms among the Finnish population and their associations with social and individual vulnerability factors. The data came from the National FINRISK 2007 Study, in which 4007 men and women aged 25-74 answered questions on heat-related cardiorespiratory symptoms in the Oulu Cold and Heat Questionnaire 2007. Logistic regression was used to calculate odds ratios (ORs), their 95 % confidence intervals (CIs), and model-predicted prevalence figures. The prevalence of heat-related cardiorespiratory symptoms was 12 %. It increased with age, from 3 % at the age of 25 years to 28 % at the age of 75 years. The symptoms were associated with pre-existing lung (OR 3.93; CI 3.01-5.13) and cardiovascular diseases (OR 2.27; 1.78-2.89); being a pensioner (OR 2.91; 1.65-5.28), unemployed (OR 2.82; 1.47-5.48), or working in agriculture (OR 2.27; 1.14-4.46) compared with working in industry; having only basic vs academic education (OR 1.98; 1.31 3.05); being female (OR 1.94; 1.51-2.50); being heavy vs light alcohol consumer (OR 1.89; 1.02-3.32); undertaking hard vs light physical work (OR 1.48;1.06 2.07); and being inactive vs active in leisure time (OR 1.97; 1.39-2.81). The adjusted prevalence of symptoms showed a wide range of variation, from 3 to 61 % depending on sex, age, professional field, education, and pre-existing lung and cardiovascular diseases. In conclusion, heat-related cardiorespiratory symptoms are commonly perceived among people with pre-existing lung or cardiovascular disease, agricultural workers, unemployed, pensioners, and people having only basic education. This information is needed for any planning and targeting measures to reduce the burden of summer heat. PMID- 27658673 TI - Engaging Patient Advocates and Other Stakeholders to Design Measures of Patient Centered Communication in Cancer Care. AB - BACKGROUND: Patient-centered communication (PCC) is an essential component of patient-centered care and contributes to patient satisfaction, health-related quality of life, and other important patient outcomes. OBJECTIVE: The aim of this study was to develop and test survey questions to assess patients' experiences with PCC in cancer care. METHODS: We used a conceptual model developed by the National Cancer Institute as our framework. The survey questions align with the six core functions of PCC defined in the model: Exchanging Information, Managing Uncertainty, Enabling Patient Self-Management, Fostering Healing Relationships, Making Decisions, and Responding to Emotions. The study focused on colorectal cancer patients. We conducted two rounds of cognitive interviewing to evaluate patients' ability to understand and provide valid answers to the PCC questions. Interviews were conducted in Maryland and North Carolina in 2014. We involved a patient advocacy group, Fight Colorectal Cancer, and a multidisciplinary panel of stakeholders throughout the measurement development process to ensure that the survey questions capture aspects of PCC that are important to patients and meet the needs of potential end users, including researchers, healthcare organizations, and health professionals. RESULTS: Patient and other stakeholder input informed revisions of draft survey questions, including changes to survey instructions, frame of reference for questions, response scales, and language. CONCLUSION: This study demonstrated the feasibility and value of engaging patients and other stakeholders in a measurement development study. The Patient Centered Outcomes Research Institute (PCORI) conceptual model of patient-centered outcomes research provides a useful guide for patient engagement in research. Research funders should call for meaningful roles for patients and other stakeholders in health research, including in the development of patient-centered outcomes. PMID- 27658675 TI - Generalizing prosodic patterns by a non-vocal learning mammal. AB - Prosody, a salient aspect of speech that includes rhythm and intonation, has been shown to help infants acquire some aspects of syntax. Recent studies have shown that birds of two vocal learning species are able to categorize human speech stimuli based on prosody. In the current study, we found that the non-vocal learning rat could also discriminate human speech stimuli based on prosody. Not only that, but rats were able to generalize to novel stimuli they had not been trained with, which suggests that they had not simply memorized the properties of individual stimuli, but learned a prosodic rule. When tested with stimuli with either one or three out of the four prosodic cues removed, the rats did poorly, suggesting that all cues were necessary for the rats to solve the task. This result is in contrast to results with humans and budgerigars, both of which had previously been studied using the same paradigm. Humans and budgerigars both learned the task and generalized to novel items, but were also able to solve the task with some of the cues removed. In conclusion, rats appear to have some of the perceptual abilities necessary to generalize prosodic patterns, in a similar though not identical way to the vocal learning species that have been studied. PMID- 27658676 TI - Experimental setting affects the performance of guppies in a numerical discrimination task. AB - A recent study found that guppies (Poecilia reticulata) can be trained to discriminate 4 versus 5 objects, a numerical discrimination typically achieved only by some mammals and birds. In that study, guppies were required to discriminate between two patches of small objects on the bottom of the tank that they could remove to find a food reward. It is not clear whether this species possesses exceptional numerical accuracy compared with the other ectothermic vertebrates or whether its remarkable performance was due to a specific predisposition to discriminate between differences in the quality of patches while foraging. To disentangle these possibilities, we trained guppies to the same numerical discriminations with a more conventional two-choice discrimination task. Stimuli were sets of dots presented on a computer screen, and the subjects received a food reward upon approaching the set with the larger numerosity. Though the cognitive problem was identical in the two experiments, the change in the experimental setting led to a much poorer performance as most fish failed even the 2 versus 3 discrimination. In four additional experiments, we varied the duration of the decision time, the type of stimuli, the length of training, and whether correction was allowed in order to identify the factors responsible for the difference. None of these parameters succeeded in increasing the performance to the level of the previous study, although the group trained with three dimensional stimuli learned the easiest numerical task. We suggest that the different results with the two experimental settings might be due to constraints on learning and that guppies might be prepared to accurately estimate patch quality during foraging but not to learn an abstract stimulus-reward association. PMID- 27658674 TI - Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia. AB - Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos+ D2 MSNs and decreased c-Fos+ non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. PMID- 27658677 TI - An mHealth Intervention Using a Smartphone App to Increase Walking Behavior in Young Adults: A Pilot Study. AB - BACKGROUND: Physical inactivity is a growing concern for society and is a risk factor for cardiovascular disease, obesity, and other chronic diseases. OBJECTIVE: This study aimed to determine the efficacy of the Accupedo-Pro Pedometer mobile phone app intervention, with the goal of increasing daily step counts in young adults. METHODS: Mobile phone users (n=58) between 17-26 years of age were randomized to one of two conditions (experimental and control). Both groups downloaded an app that recorded their daily step counts. Baseline data were recorded and followed-up at 5 weeks. Both groups were given a daily walking goal of 30 minutes, but the experimental group participants were told the equivalent goal in steps taken, via feedback from the app. The primary outcome was daily step count between baseline and follow-up. RESULTS: A significant time x group interaction effect was observed for daily step counts (P=.04). Both the experimental (P<.001) and control group (P=.03) demonstrated a significant increase in daily step counts, with the experimental group walking an additional 2000 steps per day. CONCLUSIONS: The results of this study demonstrate that a mobile phone app can significantly increase physical activity in a young adult sample by setting specific goals, using self-monitoring, and feedback. PMID- 27658679 TI - What is rheumatoid arthritis? Considering consequences of changed classification criteria. PMID- 27658678 TI - Treat-to-target (T2T) recommendations for gout. AB - OBJECTIVES: The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. METHODS: A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. CONCLUSIONS: This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon. PMID- 27658680 TI - Erratum to: Lactate-guided resuscitation saves lives: no. PMID- 27658681 TI - Clinical characterization of posterior polymorphous corneal dystrophy in patients of Indian ethnicity. AB - PURPOSE: To characterize the clinical presentation of posterior polymorphous corneal dystrophy (PPCD) in eyes of Indian ethnicity. DESIGN: Retrospective cohort study from January 1995 to December 2015. PARTICIPANTS: Patients with the diagnosis of posterior polymorphous corneal dystrophy. METHODS: Medical records of the patients were reviewed for clinical presentation. Histology of corneal specimens of those that underwent keratoplasty was assessed. MAIN OUTCOME MEASURES: Descriptive analysis of clinical condition. RESULTS: Mean age at first evaluation was 32.5 years (range 1-73 years), male:female = 35:18. Majority (44/53; 83 %) of the patients had bilateral involvement. 5/9 (44 %) patients with unilateral presentation were amblyopic in the affected eye. The clinical features documented were vesicles in 94 eyes, band-like pattern in 32 eyes, edema of varying degree in 23 eyes (12 patients, 1 patient was one eyed), and anterior segment changes in 1 eye. 8/45 (17 %) eyes had a regular astigmatism with steep axis >47 D (range 47.2-56.2 D). 16 eyes of 12 patients who had clinically evident corneal edema underwent keratoplasty. Mean age at keratoplasty was 58 years (range 1-73 years). 8 patients had penetrating keratoplasty (PK) and 8 had Descemet stripping endothelial keratoplasty (DSEK). Mean follow-up after keratoplasty was 4.2 years (1 month to 13 years). Except one, all grafts remained clear till the last follow-up. In all specimens, the Descemet membrane was grossly thickened. CONCLUSIONS: In our study, 12/53 (22.6 %) patients required keratoplasty for visually significant corneal edema. Except one, all were older adults. The patients who needed keratoplasty were bilaterally afflicted and had visually significant cornea edema in both eyes. With a mean follow-up duration of 4.2 years after keratoplasty, no recurrences were noted. PMID- 27658682 TI - Climate Change Perceptions of NY State Farmers: The Role of Risk Perceptions and Adaptive Capacity. AB - Climate change is expected to severely impact agricultural practices in many important food-producing regions, including the Northeast United States. Changing climate conditions, such as increases in the amount of rainfall, will require farmers to adapt. Yet, little is known with regard to farmers' perceptions and understandings about climate change, especially in the industrialized country context. This paper aims at overcoming this research limitation, as well as determining the existing contextual, cognitive, and psychological barriers that can prevent adoption of sustainable practices of farmers in New York State. The study is framed within the adaptive capacity and risk perception literature, and is based on a qualitative analysis of in-depth interviews with farmers in 21 farms in two counties in Central New York. The results reveal diverging views about the long-term consequences of climate change. Results also reveal that past experience remains as the most important source of information that influences beliefs and perceptions about climate change, confirming previous research. PMID- 27658683 TI - Taking the next step-Advancing bladder cancer management. PMID- 27658685 TI - Tuning Proton Conductivity by Interstitial Guest Change in Size-Adjustable Nanopores of a CuI -MOF: A Potential Platform for Versatile Proton Carriers. AB - By exploiting the breathing behavior of nanopores, we have studied for the first time the dependency of the guest-induced proton conductivity of an interpenetrated CuI metal-organic framework (CuI -MOF, [1]) on various guest molecules. Proton conductivities of over 10-3 S cm-1 under humid conditions were induced by a series of guest molecules, namely N,N-dimethylformamide, dimethyl sulfoxide, diethylamine, 1,4-dinitrobenzene, nitrobenzene, pyridine, and 1H-1,2,4 triazole. A detailed investigation of the guest-incorporated complexes revealed that low-energy proton conduction occurs under humid conditions through the Grotthuss mechanism in [1?NB] and through the vehicle mechanism in the rest of the complexes. Single-point energy computations revealed considerable stabilization upon guest encapsulation. To the best of our knowledge, [1] represents the first example in which considerably high protonic conductivity is triggered upon the facile incorporation of small molecules of such a variety. The investigation portrayed herein may be a stepping stone towards the rational design of proton-conducting materials for practical applications. PMID- 27658684 TI - ATPase and GTPase Tangos Drive Intracellular Protein Transport. AB - The GTPase superfamily of proteins provides molecular switches to regulate numerous cellular processes. The 'GTPase switch' paradigm, in which external regulatory factors control the switch of a GTPase between 'on' and 'off' states, has been used to interpret the regulatory mechanism of many GTPases. However, recent work unveiled a class of nucleotide hydrolases that do not adhere to this classical paradigm. Instead, they use nucleotide-dependent dimerization cycles to regulate key cellular processes. In this review article, recent studies of dimeric GTPases and ATPases involved in intracellular protein targeting are summarized. It is suggested that these proteins can use the conformational plasticity at their dimer interface to generate multiple points of regulation, thereby providing the driving force and spatiotemporal coordination of complex cellular pathways. PMID- 27658687 TI - What Lies Beneath: Acropachy Hiding Subungual Osteochondroma. PMID- 27658686 TI - Ectomycorrhizal fungal response to warming is linked to poor host performance at the boreal-temperate ecotone. AB - Rising temperatures associated with climate change have been shown to negatively affect the photosynthetic rates of boreal forest tree saplings at their southern range limits. To quantify the responses of ectomycorrhizal (EM) fungal communities associated with poorly performing hosts, we sampled the roots of Betula papyrifera and Abies balsamea saplings growing in the B4Warmed (Boreal Forest Warming at an Ecotone in Danger) experiment. EM fungi on the root systems of both hosts were compared from ambient and +3.4 degrees C air and soil warmed plots at two sites in northern Minnesota. EM fungal communities were assessed with high-throughput sequencing along with measures of plant photosynthesis, soil temperature, moisture, and nitrogen. Warming selectively altered EM fungal community composition at both the phylum and genus levels, but had no significant effect on EM fungal operational taxonomic unit (OTU) diversity. Notably, warming strongly favored EM Ascomycetes and EM fungi with short-contact hyphal exploration types. Declining host photosynthetic rates were also significantly inversely correlated with EM Ascomycete and EM short-contact exploration type abundance, which may reflect a shift to less carbon demanding fungi due to lower photosynthetic capacity. Given the variation in EM host responses to warming, both within and between ecosystems, better understanding the link between host performance and EM fungal community structure will to clarify how climate change effects cascade belowground. PMID- 27658688 TI - Precancerous Skin Lesions. AB - Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today. PMID- 27658690 TI - Digitizing paper electrocardiograms: Status and challenges. AB - The paper electrocardiogram (ECG) has been widely used for cardiac assessment for well over a century. ECGs can be obtained quickly and cheaply. For this reason, an ever-growing amount of paper ECG records continue to accumulate, some of which are stored into a paper-only format. Converting paper ECGs into digital form has been proposed as the most efficient means to store and analyze an otherwise cumbersome paper archive. In this article, a literature review was conducted for conversion algorithms, criticisms of said algorithms, applications, and standardization efforts. The algorithms were compared in tabulated form. Key functions that have advanced the conversion algorithms as well as remaining challenges are discussed. PMID- 27658689 TI - Management of Biologic Therapy in Moderate to Severe Psoriasis in Surgical Patients: Data From the Spanish Biobadaderm Registry. AB - BACKGROUND AND OBJECTIVE: We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. METHODS: Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. RESULTS: Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. CONCLUSION: Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size. PMID- 27658691 TI - Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine. AB - BACKGROUND: The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. METHODS: In this double blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. RESULTS: Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. CONCLUSIONS: The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV. PMID- 27658692 TI - The Matrine Derivate MASM Prolongs Survival, Attenuates Inflammation, and Reduces Organ Injury in Murine Established Lethal Sepsis. AB - BACKGROUND: MASM, a novel derivative of matrine, has inhibitory effects on activation of macrophages, dendritic cells, and hepatic stellate cells and binds to ribosomal protein S5 (RPS5). This study was designed to evaluate the effect of MASM on murine-established lethal sepsis and its mechanisms. METHODS: Mouse peritoneal macrophages and RAW264.7 cells that were infected with recombinant lentiviruses encoding shRPS5 were incubated with lipopolysaccharide (LPS) in the absence or presence of MASM in vitro. Endotoxemia induced by LPS injection and sepsis induced by cecal ligation and puncture was followed by MASM treatment. RESULTS: MASM markedly attenuated LPS-induced release and messenger RNA expression of tumor necrosis factor alpha, interleukin 6, and NO/inducible NO synthase in murine peritoneal macrophages and RAW264.7 cells. Meanwhile, MASM inhibited LPS-induced activation of nuclear factor kappaB and MAPK pathways. Consistently, RPS5 suppressed LPS-induced inflammatory responses and at least in part mediated the antiinflammatory effect of MASM in vitro. Remarkably, delayed administration of MASM could significantly reduce mortality in mouse sepsis models, which was associated with the reduction in the inflammatory response, the attenuation in multiple organ injury, and the enhanced bacterial clearance. CONCLUSIONS: MASM could be further explored for the treatments of sepsis, especially for administration later after the onset of sepsis. PMID- 27658694 TI - Thomas ED, Buckner CD, Rudolph RH, et al. Allogeneic marrow grafting for hematologic malignancy using HL-A matched donor-recipient sibling pairs. Blood. 1971;38(3):267-287. PMID- 27658693 TI - Hepatitis B Virus (HBV) Load Response to 2 Antiviral Regimens, Tenofovir/Lamivudine and Lamivudine, in HIV/ HBV-Coinfected Pregnant Women in Guangxi, China: The Tenofovir in Pregnancy (TiP) Study. AB - BACKGROUND: There is limited information on antiviral therapy for hepatitis B virus (HBV) infection among pregnant women coinfected with human immunodeficiency virus (HIV) and HBV. METHODS: A phase 2 randomized, controlled trial of a regimen containing tenofovir (TDF)/lamivudine (3TC) and a regimen containing 3TC in HIV/HBV-coinfected pregnant women in China. The HBV virological response was compared in study arms. RESULTS: The median decline in the HBV DNA level was 2.60 log10 copies/mL in the TDF/3TC arm and 2.24 log10 copies/mL in the 3TC arm (P = .41). All women achieved HBV DNA levels of <6 log10 copies/mL at delivery. CONCLUSIONS: Initiation of either regimen led to achievement of HBV DNA levels below the threshold associated with perinatal HBV transmission. CLINICAL TRIALS REGISTRATION: NCT01125696. PMID- 27658695 TI - Blind men and the refractory ITP elephant. PMID- 27658696 TI - Unchanneling cardiac iron in humans. PMID- 27658697 TI - BV for HL: can the responses last? PMID- 27658698 TI - Turning it down a Notch. PMID- 27658699 TI - EBV, an inhibited receptor kinase, and lymphoma. PMID- 27658700 TI - When is a thrombogenic matrix not thrombogenic? PMID- 27658701 TI - RBC storage lesions. PMID- 27658703 TI - Behavioural and neural modulation of win-stay but not lose-shift strategies as a function of outcome value in Rock, Paper, Scissors. AB - Competitive environments in which individuals compete for mutually-exclusive outcomes require rational decision making in order to maximize gains but often result in poor quality heuristics. Reasons for the greater reliance on lose-shift relative to win-stay behaviour shown in previous studies were explored using the game of Rock, Paper, Scissors and by manipulating the value of winning and losing. Decision-making following a loss was characterized as relatively fast and relatively inflexible both in terms of the failure to modulate the magnitude of lose-shift strategy and the lack of significant neural modulation. In contrast, decision-making following a win was characterized as relatively slow and relatively flexible both in terms of a behavioural increase in the magnitude of win-stay strategy and a neural modulation of feedback-related negativity (FRN) and stimulus-preceding negativity (SPN) following outcome value modulation. The win-stay/lose-shift heuristic appears not to be a unified mechanism, with the former relying on System 2 processes and the latter relying on System 1 processes. Our ability to play rationally appears more likely when the outcome is positive and when the value of wins are low, highlighting how vulnerable we can be when trying to succeed during competition. PMID- 27658702 TI - Oxygen tension modulates the effects of TNFalpha in compressed chondrocytes. AB - OBJECTIVE AND DESIGN: Oxygen tension and biomechanical signals are factors that regulate inflammatory mechanisms in chondrocytes. We examined whether low oxygen tension influenced the cells response to TNFalpha and dynamic compression. MATERIALS AND METHODS: Chondrocyte/agarose constructs were treated with varying concentrations of TNFalpha (0.1-100 ng/ml) and cultured at 5 and 21 % oxygen tension for 48 h. In separate experiments, constructs were subjected to dynamic compression (15 %) and treated with TNFalpha (10 ng/ml) and/or L-NIO (1 mM) at 5 and 21 % oxygen tension using an ex vivo bioreactor for 48 h. Markers for catabolic activity (NO, PGE2) and tissue remodelling (GAG, MMPs) were quantified by biochemical assay. ADAMTS-5 and MMP-13 expression were examined by real-time qPCR. 2-way ANOVA and a post hoc Bonferroni-corrected t test were used to analyse data. RESULTS: TNFalpha dose-dependently increased NO, PGE2 and MMP activity (all p < 0.001) and induced MMP-13 (p < 0.05) and ADAMTS-5 gene expression (pp < 0.01) with values greater at 5 % oxygen tension than 21 %. The induction of catabolic mediators by TNFalpha was reduced by dynamic compression and/or L-NIO (all p < 0.001), with a greater inhibition observed at 5% than 21 %. The stimulation of GAG synthesis by dynamic compression was greater at 21 % than 5 % oxygen tension and this response was reduced with TNFalpha or reversed with L-NIO. CONCLUSIONS: The present findings revealed that TNFalpha increased production of NO, PGE2 and MMP activity at 5 % oxygen tension. The effects induced by TNFalpha were reduced by dynamic compression and/or the NOS inhibitor, linking both types of stimuli to reparative activities. Future therapeutics should develop oxygen-sensitive antagonists which are directed to interfering with the TNFalpha-induced pathways. PMID- 27658705 TI - Surface-Functionalized Electrospun Titania Nanofibers for the Scavenging and Recycling of Precious Metal Ions. AB - Precious metals are widely used as catalysts in industry. It is of critical importance to keep the precious metal ions leached from catalysts at a level below one part per million (ppm) in the final products and to recycle the expensive precious metals. Here we demonstrate a simple and effective method for scavenging precious metal ions from an aqueous solution and thereby reduce their concentrations down to the parts per billion (ppb) level. The key component is a filtration membrane comprised of titania (TiO2 ) nanofibers whose surface has been functionalized with a silane bearing amino or thiol group. When operated under continuous flow at a rate of 1 mL min-1 and at room temperature, up to 99.95 % of the Pd2+ ions could be removed from a stock solution with an initial concentration of 100 ppm. This work offers a viable strategy not only for the removal of precious metal ions but also for recovering and further recycling them for use as catalysts. For example, the captured Pd2+ ions could be converted to nanoparticles and used as catalysts for organic reactions such as Suzuki coupling in a continuous flow reactor. This system can be potentially applied to pharmaceutical industry and waste stream treatment. PMID- 27658704 TI - Baicalin attenuates bleomycin-induced pulmonary fibrosis via adenosine A2a receptor related TGF-beta1-induced ERK1/2 signaling pathway. AB - BACKGROUND: Baicalin has been reported to have anti-fibrosis effect; however, its mechanism still remains to be elucidated. Adenosine A2a receptor (A2aR) is a novel inflammation regulator, and transforming growth factor-beta1 (TGF-beta1) induced extracellular signal regulated kinase1/2 (ERK1/2) signaling pathway plays an important role in idiopathic pulmonary fibrosis (IPF). This study was to explore the relationship of A2aR and TGF-beta1-induced ERK1/2 in bleomycin (BLM) induced pulmonary fibrosis in mice, and to investigate whether A2aR mediate the anti-fibrosis effect of Baicalin on BLM-induced pulmonary fibrosis. METHODS: The A2aR-/- and A2aR+/+ mice were respectively divided into three groups: control group, model group, baicalin group. Pulmonary fibrosis was induced in mice of model groups by intratracheal instillation of bleomycin, and baicalin was administered in mice of baicalin groups daily for 28 days. Histopathological and ultrastructural changes of lung tissues were evaluated. Lung coefficient and the levels of hydroxyproline (HYP) in lung tissues were measured at the same time. The levels of serum TGF-beta1 were measured by ELISA. The expression of TGF beta1, ERK1/2, p-ERK1/2 and A2aR were detected by western blot and immunohistochemical staining techniques. RESULTS: Severe lung fibrosis was observed in the bleomycin-treated mice on day 28. The histopathological findings and collagen content of lung tissues were much severer/higher in A2aR-/- mice than in A2aR+/+ mice. We also showed that TGF-beta1 and p-ERK1/2 were upregulated in bleomycin-treated mice and expressed higher in A2aR-/- mice compared to A2aR+/+ mice. Besides, bleomycin-treated A2aR+/+ mice had increased A2aR level in lungs. However, long-term treatment with baicalin in A2aR-/- and A2aR+/+ mice significantly ameliorated the histopathological changes in lungs. Moreover, Increased TGF-beta1 and p-ERK1/2 expressions in bleomycin-treated A2aR-/- and A2aR+/+ mice were obviously diminished by baicalin. The baicalin-treated A2aR-/- mice had severer lung fibrosis and higher expressions of TGF-beta1 and p-ERK1/2 than A2aR+/+ mice. Baicalin has also upregulated the expression of A2aR in A2aR+/+ mice. CONCLUSIONS: Genetic inactivation of A2aR exacerbated the pathological processes of bleomycin-induced pulmonary fibrosis. Together, baicalin could inhibit BLM-induced pulmonary fibrosis by upregulating A2aR, suggesting A2aR as a therapeutic target of baicalin for the treatment of pulmonary fibrosis. PMID- 27658707 TI - Amyand's hernia with appendicitis masquerading as Fournier's gangrene: a case report and review of the literature. AB - BACKGROUND: The incarceration of an appendix within an inguinal hernia sac is known as Amyand's hernia. Appendicitis in Amyand's hernia accounts for 0.1 % of the cases. An aggressive necrotizing infection of the genitalia and perineum, called Fournier's gangrene, can rapidly progress to sepsis and death. We describe a rare case of Fournier's gangrene complicating Amyand's inguinal hernia which has rarely been reported in the literature. CASE PRESENTATION: This case report describes the presentation and management of a 47-year-old Chinese man who presented with pus discharge from his right inguinoscrotal region and lower abdominal pain with clinical signs of Fournier's gangrene. On surgical exploration, a complicated Amyand's hernia (Losanoff and Basson classification type 4) was found to be the cause of his Fournier's gangrene. CONCLUSIONS: A perforated appendix within an inguinal hernia causing Fournier's gangrene is rarely seen in clinical practice. The diagnosis of this condition is almost always made intraoperatively. Early recognition and awareness of perforated appendicitis within an inguinal hernia sac as one of the causes of Fournier's gangrene and good surgical technique in such cases are the keys to success when dealing with this surgical issue. In complicated presentations of Amyand's hernia, an appendicectomy with anatomical repair is the best treatment. It is better to avoid meshplasty. PMID- 27658706 TI - Primary triage nurses do not divert patients away from the emergency department at times of high in-hospital bed occupancy - a retrospective cohort study. AB - BACKGROUND: Emergency department (ED) overcrowding is frequently described in terms of input- throughput and output. In order to reduce ED input, a concept called primary triage has been introduced in several Swedish EDs. In short, primary triage means that a nurse separately evaluates patients who present in the Emergency Department (ED) and either refers them to primary care or discharges them home, if their complaints are perceived as being of low acuity. The aim of the present study is to elucidate whether high levels of in-hospital bed occupancy are associated with decreased permeability in primary triage. The appropriateness of discharges from primary triage is assessed by 72-h revisits to the ED. METHODS: The study is a retrospective cohort study on administrative data from the ED at a 420-bed hospital in southern Sweden from 2011-2012. In addition to crude comparisons of proportions experiencing each outcome across strata of in hospital bed occupancy, multivariate models are constructed in order to adjust for age, sex and other factors. RESULTS: A total of 37,129 visits to primary triage were included in the study. 53.4 % of these were admitted to the ED. Among the cases referred to another level of care, 8.8 % made an unplanned revisit to the ED within 72 h. The permeability of primary triage was not decreased at higher levels of in-hospital bed occupancy. Rather, the permeability was slightly higher at occupancy of 100-105 % compared to <95 % (OR 1.09 95 % CI 1.02-1.16). No significant association between in-hospital bed occupancy and the probability of 72-h revisits was observed. CONCLUSIONS: The absence of a decreased permeability of primary triage at times of high in-hospital bed occupancy is reassuring, as the opposite would have implied that patients might be denied entry not only to the hospital, but also to the ED, when in-hospital beds are scarce. PMID- 27658708 TI - Depletion of gamma-glutamylcyclotransferase inhibits breast cancer cell growth via cellular senescence induction mediated by CDK inhibitor upregulation. AB - BACKGROUND: Chromosome 7 open reading frame 24 (C7orf24) was originally identified as a highly expressed protein in various types of cancer, and later shown to be a gamma-glutamylcyclotransferase (GGCT). GGCT depletion in cancer cells has anti-proliferative effects in vitro and in vivo, and it is therefore considered a promising candidate as a therapeutic target. However, the cellular events induced by GGCT depletion remain unclear. METHODS: GGCT was depleted by siRNA in MCF7, MDA-MB-231, PC3, A172, Hela, and LNCaP cells. Induction of cellular senescence was evaluated with senescence-associated beta-galactosidase (SA-beta-Gal) staining. Expression levels of p21WAF1/CIP1 and p16INK4A were assessed by qRT-PCR and Western blotting. Effects of simultaneous double knockdown of p21WAF1/CIP1 and p16INK4A together with GGCT on cell cycle regulation and cell growth was measured by flow cytometry, and trypan blue dye exclusion test. RESULTS: We found that GGCT knockdown induces significant cellular senescence in various cancer cells. Cyclin dependent kinase inhibitor p21WAF1/CIP1 and/or p16INK4A were upregulated in all cell lines tested. Simultaneous knockdown of p21WAF1/CIP1 recovered the cell cycle arrest, attenuated cellular senescence induction, and rescued the subsequent growth inhibition in GGCT-silenced MCF7 breast cancer cells. In contrast, in GGCT silenced MDA-MB-231 breast cancer cells, GGCT depletion upregulated p16INK4A, which played a regulatory role in senescence induction, instead of p21WAF1/CIP1. CONCLUSIONS: Our findings demonstrate that induction of cellular senescence mediated by the upregulation of cyclin-dependent kinase inhibitors is a major event underlying the anti-proliferative effect of GGCT depletion in breast cancer cells, highlighting the potential of GGCT blockade as a therapeutic strategy to induce cellular senescence. PMID- 27658709 TI - Comparing fluorescence-based cell-free assays for the assessment of antioxidative capacity of high-density lipoproteins. AB - BACKGROUND: Population studies have shown an inverse association between high density lipoprotein (HDL) cholesterol levels and risk of coronary heart disease (CHD). HDL has different functions, including the ability to protect biological molecules from oxidation. Our aim was to evaluate the performance of two fluorescence-based assays in assessing the antioxidative capacity of HDL. METHODS: We compared the antioxidative capacity of HDL with the phospholipid 2',7'-dichlorodihydrofluorescein (DCF) assay and the dihydrorhodamine 123 (DHR) assay in controls and in subjects at increased risk of CHD, including subjects with established CHD, and subjects with elevated plasma triglycerides (TG), serum amyloid A (SAA), or myeloperoxidase (MPO) levels. RESULTS: The antioxidative capacity of HDL, as measured by the DCF assay, was significantly lower in both CHD and high-TG patients than in controls (p < 0.001 and p = 0.004, respectively). Interestingly, the mean antioxidative capacity of HDL in high-SAA subjects was significantly higher (p < 0.03), while in high-MPO subjects was similar to controls. When the DHR assay was used we did not find differences in HDL's antioxidative capacity between CHD patients and controls but we found higher antioxidative capacity in high-SAA subjects compared to controls. CONCLUSIONS: Only the DCF assay could detect significant differences in the antioxidative capacity of HDL between controls and CHD subjects. Practical use of both assays for the assessment of antioxidative capacity of HDL is limited by the large overlap in values among groups. The antioxidative activity of HDL in patients who have elevated SAA levels needs to be reassessed. PMID- 27658712 TI - The molecular choreography of protein synthesis: translational control, regulation, and pathways. AB - Translation of proteins by the ribosome regulates gene expression, with recent results underscoring the importance of translational control. Misregulation of translation underlies many diseases, including cancer and many genetic diseases. Decades of biochemical and structural studies have delineated many of the mechanistic details in prokaryotic translation, and sketched the outlines of eukaryotic translation. However, translation may not proceed linearly through a single mechanistic pathway, but likely involves multiple pathways and branchpoints. The stochastic nature of biological processes would allow different pathways to occur during translation that are biased by the interaction of the ribosome with other translation factors, with many of the steps kinetically controlled. These multiple pathways and branchpoints are potential regulatory nexus, allowing gene expression to be tuned at the translational level. As research focus shifts toward eukaryotic translation, certain themes will be echoed from studies on prokaryotic translation. This review provides a general overview of the dynamic data related to prokaryotic and eukaryotic translation, in particular recent findings with single-molecule methods, complemented by biochemical, kinetic, and structural findings. We will underscore the importance of viewing the process through the viewpoints of regulation, translational control, and heterogeneous pathways. PMID- 27658710 TI - Antigen processing and immune regulation in the response to tumours. AB - The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8+ cytotoxic and CD4+ helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8+ cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4+ T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8+ cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets. PMID- 27658711 TI - Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: an observational study. AB - BACKGROUND: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. METHODS: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. RESULTS: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61 68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. DISCUSSION: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. CONCLUSION: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services. PMID- 27658713 TI - Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis. AB - Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by in vivo electroporation. Subclinical MG was subsequently induced with a low dose of anti-AChR monoclonal antibody 35. Neuromuscular transmission was significantly impaired in Dok-7-siRNA electroporated legs compared with the contralateral control legs, which correlated with a reduction of AChR protein levels at the neuromuscular junction (approximately 25%) in Dok-7-siRNA-electroporated muscles, compared with contralateral control muscles. These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack. PMID- 27658715 TI - Note of Concern. AB - This Note of Concern relates to Al-Gayyar et al Am J Pathol 177:1187-1197 and Correction 185:1795-1796. PMID- 27658714 TI - Braf Mutations Initiate the Development of Rat Gliomas Induced by Postnatal Exposure to N-Ethyl-N-Nitrosourea. AB - A single dose of N-ethyl-N-nitrosourea (ENU) during late prenatal or early postnatal development induces a high incidence of malignant schwannomas and gliomas in rats. Although T->A mutations in the transmembrane domain of the Neu (c-ErbB-2) gene are the driver mutations in ENU-induced malignant schwannomas, the molecular basis of ENU-induced gliomas remains enigmatic. We performed whole genome sequencing of gliomas that developed in three BDIV and two BDIX rats exposed to a single dose of 80 mg ENU/kg body weight on postnatal day one. T:A >A:T and T:A->C:G mutations, which are typical for ENU-induced mutagenesis, were predominant (41% to 55% of all somatic single nucleotide mutations). T->A mutations were identified in all five rat gliomas at Braf codon 545 (V545E), which corresponds to the human BRAF V600E. Additional screening revealed that 33 gliomas in BDIV rats and 12 gliomas in BDIX rats all carried a Braf V545E mutation, whereas peritumoral brain tissue of either strain had the wild-type sequence. The gliomas were immunoreactive to BRAF V600E antibody. These results indicate that Braf mutation is a frequent early event in the development of rat gliomas caused by a single dose of ENU. PMID- 27658716 TI - Epigenetic Profiling of CUP. AB - DNA methylation profiling may have potential in unmasking the origin of tumors classified as cancer of unknown primary. A diagnostic assay developed by the researchers, EPICUP, predicted the primary tumor site in 87% of 216 cases, and these predictions were subsequently verified through various tests, including immunohistochemistry. PMID- 27658717 TI - Pinpointing a Factor in Myeloma Bone Disease. AB - A recent study implicates thymidine phosphorylase in myeloma-induced bone disease and suggests that inhibiting the enzyme may be a viable therapeutic option. Thymidine phosphorylase provokes osteolytic lesions by disrupting the balance between bone resorption and formation, shifting it toward a net loss of bone tissue. PMID- 27658718 TI - Flipper strokes can predict energy expenditure and locomotion costs in free ranging northern and Antarctic fur seals. AB - Flipper strokes have been proposed as proxies to estimate the energy expended by marine vertebrates while foraging at sea, but this has never been validated on free-ranging otariids (fur seals and sea lions). Our goal was to investigate how well flipper strokes correlate with energy expenditure in 33 foraging northern and Antarctic fur seals equipped with accelerometers, GPS, and time-depth recorders. We concomitantly measured field metabolic rates with the doubly labelled water method and derived activity-specific energy expenditures using fine-scale time-activity budgets for each seal. Flipper strokes were detected while diving or surface transiting using dynamic acceleration. Despite some inter species differences in flipper stroke dynamics or frequencies, both species of fur seals spent 3.79 +/- 0.39 J/kg per stroke and had a cost of transport of ~1.6 1.9 J/kg/m while diving. Also, flipper stroke counts were good predictors of energy spent while diving (R2 = 0.76) and to a lesser extent while transiting (R2 = 0.63). However, flipper stroke count was a poor predictor overall of total energy spent during a full foraging trip (R2 = 0.50). Amplitude of flipper strokes (i.e., acceleration amplitude * number of strokes) predicted total energy expenditure (R2 = 0.63) better than flipper stroke counts, but was not as accurate as other acceleration-based proxies, i.e. Overall Dynamic Body Acceleration. PMID- 27658720 TI - Improvement in verbal memory performance in depressed in-patients after treatment with electroconvulsive therapy. AB - OBJECTIVE: Electroconvulsive therapy (ECT) is a highly effective and well tolerated therapy for severe and treatment-resistant depression. Cognitive side effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself. METHODS: Patients suffering from a severe episode of depression were treated with either ECT or treatment as usual (TAU) in an in-patient setting. Matched healthy participants served as controls (HC). Verbal memory was tested with the California Verbal Learning Test (CVLT) before the specific treatment started (ECT = 15, TAU = 16, HC = 31) and 2 months after the last ECT session or 2 months after discharge respectively. RESULTS: Before the specific treatment started, depressed patients performed substantially worse compared with HC in total, short and long-delay recall in the CVLT, while the ECT group showed the worst performance. More severely depressed patients showed worse performances in these measures. Intriguingly, verbal memory showed a significant improvement in ECT treated patients, but not in the other groups. No differences between the groups were found at follow-up. CONCLUSION: Contrary to the widely feared assumption that ECT has long-term impact on memory functions, we found evidence that ECT is superior to TAU in improving verbal memory in depressed patients. PMID- 27658721 TI - Subnatural-linewidth biphotons from a Doppler-broadened hot atomic vapour cell. AB - Entangled photon pairs, termed as biphotons, have been the benchmark tool for experimental quantum optics. The quantum-network protocols based on photon-atom interfaces have stimulated a great demand for single photons with bandwidth comparable to or narrower than the atomic natural linewidth. In the past decade, laser-cooled atoms have often been used for producing such biphotons, but the apparatus is too large and complicated for engineering. Here we report the generation of subnatural-linewidth (<6 MHz) biphotons from a Doppler-broadened (530 MHz) hot atomic vapour cell. We use on-resonance spontaneous four-wave mixing in a hot paraffin-coated 87Rb vapour cell at 63 degrees C to produce biphotons with controllable bandwidth (1.9-3.2 MHz) and coherence time (47-94 ns). Our backward phase-matching scheme with spatially separated optical pumping is the key to suppress uncorrelated photons from resonance fluorescence. The result may lead towards miniature narrowband biphoton sources. PMID- 27658719 TI - In vivo T-cell activation by a monoclonal alphaCD3epsilon antibody induces preterm labor and birth. AB - PROBLEM: Activated/effector T cells seem to play a role in the pathological inflammation associated with preterm labor. The aim of this study was to determine whether in vivo T-cell activation by a monoclonal alphaCD3epsilon antibody induces preterm labor and birth. METHOD OF STUDY: Pregnant B6 mice were intraperitoneally injected with a monoclonal alphaCD3epsilon antibody or its isotype control. The gestational age, the rates of preterm birth and pup mortality at birth as well as the fetal heart rate and umbilical artery pulsatility index were determined. RESULTS: Injection of a monoclonal alphaCD3epsilon antibody led to preterm labor/birth (alphaCD3epsilon 83 +/- 16.97% [10/12] vs isotype 0% [0/8]) and increased the rate of pup mortality at birth (alphaCD3epsilon 87.30 +/- 8.95% [77/85] vs isotype 4.91 +/- 4.34% [3/59]). In addition, injection of a monoclonal alphaCD3epsilon antibody decreased the fetal heart rate and increased the umbilical artery pulsatility index when compared to the isotype control. CONCLUSION: In vivo T-cell activation by a monoclonal alphaCD3epsilon antibody in late gestation induces preterm labor and birth. PMID- 27658723 TI - The UPR inducer DPP23 inhibits the metastatic potential of MDA-MB-231 human breast cancer cells by targeting the Akt-IKK-NF-kappaB-MMP-9 axis. AB - (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP23) is a synthetic polyphenol derivative that selectively induces apoptosis in cancer cells through the unfolded protein response pathway. In the present study, we evaluated the effect of DPP23 on tumour invasion and metastasis. Here, we show that DPP23 inhibited tumour necrosis factor alpha (TNFalpha)-induced motility, F actin formation, and the invasive capability of MDA-MB-231 cells. DPP23 inhibited NF-kappaB-dependent MMP-9 expression at the transcriptional level. Akt is involved in the activation of IKK, an upstream regulator of NF-kappaB. DPP23 inhibited IKK and Akt, and knockdown of Akt2 significantly inhibited TNFalpha induced IKK phosphorylation. We found that DPP23 bound to the catalytic domain of Akt2, as revealed by an in silico molecular docking analysis. These results suggest that DPP23 prevents TNFalpha-induced invasion of highly metastatic MDA-MB 231 breast cancer cells by inhibiting Akt-IKK-NF-kappaB axis-mediated MMP-9 gene expression. In addition, DPP23 attenuated experimental liver metastasis in a syngenic intrasplenic transplantation model using 4T1 mouse mammary carcinoma cells. Collectively, these results suggest that DPP23 could be used as a potential platform for the prevention of invasion and metastasis of early-stage breast cancer or as an adjuvant for chemo/radiotherapy. PMID- 27658722 TI - Gut microbiota Modulated by Probiotics and Garcinia cambogia Extract Correlate with Weight Gain and Adipocyte Sizes in High Fat-Fed Mice. AB - Results of recent studies on gut microbiota have suggested that obesogenic bacteria exacerbate obesity and metabolic dysfunction in the host when fed a high fat diet (HFD). In order to explore obesity-associated bacterial candidates and their response to diet, the composition of faecal bacterial communities was investigated by analyzing 16S rRNA gene sequences in mice. Dietary intervention with probiotics and Garcinia cambogia extract attenuated weight gain and adipocyte size in HFD-fed mice. To identify obesity-causative microbiota, two statistical analyses were performed. Forty-eight bacterial species were found to overlap between the two analyses, indicating the commonly identified species as diet-driven and obesity-associated, which would make them strong candidates for host-microbiome interaction on obesity. Finally, correlation based network analysis between diet, microbe, and host revealed that Clostridium aminophilum, a hyper-ammonia-producing bacterium, was highly correlated with obesity phenotypes and other associated bacteria, and shown to be suppressed by the combination of probiotics and Garcinia cambogia extract. Results of the present study suggest that probiotics and Garcinia cambogia extract alleviate weight gain and adiposity, in part via differentially modulating the composition of gut microbiota in HFD fed mice. PMID- 27658724 TI - Discordance in cathepsin B and cystatin C expressions in bronchoalveolar fluids between murine bleomycin-induced fibrosis and human idiopathic fibrosis. AB - The activity of cysteine cathepsin B increased markedly in lung homogenates and in bronchoalveolar lavage fluids (BALF) of the mouse model of bleomycin-induced lung fibrosis after 14 days of challenge. In contrast the level of the cysteine cathepsin inhibitor cystatin C was unaffected in BALF of wild-type and cathepsin B-deficient mice. Therefore, murine cystatin C is not a reliable marker of fibrosis during bleomycin-induced lung fibrosis. Current data are in sharp contrast to previous analysis carried on human BALF from patients with idiopathic pulmonary fibrosis, for which the level of cathepsin B remained unchanged while cystatin C was significantly increased. PMID- 27658725 TI - Myeloid cells as orchestrators of the tumor microenvironment: novel targets for nanoparticular cancer therapy. AB - Macrophages, myeloid-derived suppressor cells and tolerogenic dendritic cells are central players of a heterogeneous myeloid cell population, with the ability to suppress innate and adaptive immune responses and thus to promote tumor growth. Their influx and local proliferation are mainly induced by the cancers themselves, and their numbers in the tumor microenvironment and the peripheral blood correlate with decreased survival. Therapeutic targeting these innate immune cells, either aiming at their elimination or polarization toward tumor suppressive cells is an attractive novel approach to control tumor progression and block metastasis. We review the current understanding of cancer immunology including immune surveillance and immune editing in the context of these prominent innate suppressor cells, and their targetability by nanoparticular immunotherapy with small molecules or siRNA. PMID- 27658726 TI - Neuroendocrinology: New hormone treatment for obesity caused by POMC-deficiency. PMID- 27658727 TI - Mechanisms of diabetes mellitus-induced bone fragility. AB - The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus. PMID- 27658728 TI - Bone Tissue Regeneration - Application of Mesenchymal Stem Cells and Cellular and Molecular Mechanisms. AB - BACKGROUND & OBJECTIVE: The regeneration of damaged bone tissues to a pre-disease state has been a major goal for both clinicians and researchers worldwide. However, critical-sized bone defects which are unable to heal completely are a major clinical concern because effective, evidencebased regenerative therapy is still missing. Bone tissue engineering, aiming at providing novel and effective materials to promote bone regeneration, has been considered as a promising alternative to the traditional use of autografts, allografts and xenografts based on the fact that engineered bone tissue has limitless supply and has no disease transmission. Mesenchymal stem cells (MSCs) can be derived from various adult tissues such as adipose tissues, dental follicles of wisdom teeth, bone marrow, dental pulp, gingiva, etc., which do not raise any ethical concerns. Furthermore, the application of MSCs in bone tissue engineering has moved to the preclinical stage, and an ex vivo cell manufacturing procedure for obtaining high quality, bioactive MSCs from human bone marrow has been approved by the US Food and Drug Administration (FDA). SUMMARY: In this review, we summarized the cell sources and biological characteristics of MSCs, discussed the in vivo functions of MSCs during bone regeneration, and briefly introduced the strategies for the application of MSCs in bone tissue engineering. Further research efforts are still needed to facilitate the application of MSCs in enhancing bone regeneration. PMID- 27658729 TI - Sexually dimorphic gene expressions in eels: useful markers for early sex assessment in a conservation context. AB - Environmental sex determination (ESD) has been detected in a range of vertebrate reptile and fish species. Eels are characterized by an ESD that occurs relatively late, since sex cannot be histologically determined before individuals reach 28 cm. Because several eel species are at risk of extinction, assessing sex at the earliest stage is a crucial management issue. Based on preliminary results of RNA sequencing, we targeted genes susceptible to be differentially expressed between ovaries and testis at different stages of development. Using qPCR, we detected testis-specific expressions of dmrt1, amh, gsdf and pre-miR202 and ovary-specific expressions were obtained for zar1, zp3 and foxn5. We showed that gene expressions in the gonad of intersexual eels were quite similar to those of males, supporting the idea that intersexual eels represent a transitional stage towards testicular differentiation. To assess whether these genes would be effective early molecular markers, we sampled juvenile eels in two locations with highly skewed sex ratios. The combined expression of six of these genes allowed the discrimination of groups according to their potential future sex and thus this appears to be a useful tool to estimate sex ratios of undifferentiated juvenile eels. PMID- 27658730 TI - Region-specific growth restriction of brain following preterm birth. AB - Regional brain sizes of very-preterm infants at term-equivalent age differ from those of term-born peers, which have been linked with later cognitive impairments. However, dependence of regional brain volume loss on gestational age has not been studied in detail. To investigate the spatial pattern of brain growth in neonates without destructive brain lesions, head MRI of 189 neonates with a wide range of gestational age (24-42 weeks gestation) was assessed using simple metrics measurements. Dependence of MRI findings on gestational age at birth (Agebirth) and the corrected age at MRI scan (AgeMRI) were assessed. The head circumference was positively correlated with AgeMRI, but not Agebirth. The bi-parietal width, deep grey matter area and the trans-cerebellar diameter were positively correlated with both Agebirth and AgeMRI. The callosal thickness (positive), atrial width of lateral ventricle (negative) and the inter hemispheric distance (negative) were exclusively correlated with Agebirth. The callosal thickness and cerebral/cerebellar transverse diameters showed predominant dependence on Agebirth over AgeMRI, suggesting that brain growth after preterm-birth was considerably restricted or even became negligible compared with that in utero. Such growth restriction after preterm birth may extensively affect relatively more matured infants, considering the linear relationships observed between brain sizes and Agebirth. PMID- 27658731 TI - Substantial Band-Gap Tuning and a Strain-Controlled Semiconductor to Gapless/Band Inverted Semimetal Transition in Rutile Lead/Stannic Dioxide. AB - By first-principle calculations, we have systematically studied the effect of strain/pressure on the electronic structure of rutile lead/stannic dioxide (PbO2/SnO2). We find that pressure/strain has a significant impact on the electronic structure of PbO2/SnO2. Not only can the band gap be substantially tuned by pressure/strain, but also a transition between a semiconductor and a gapless/band-inverted semimetal can be manipulated. Furthermore, the semimetallic state is robust under strain, indicating a bright perspective for electronics applications. In addition, a practical approach to realizing strain in SnO2 is then proposed by substituting tin (Sn) with lead (Pb), which also can trigger the transition from a large-band-gap to a moderate-gap semiconductor with enhanced electron mobility. This work is expected to provide guidance for full utilization of the flexible electronic properties in PbO2 and SnO2. PMID- 27658733 TI - Nationwide review of mixed and non-mixed components from different manufacturers in total hip arthroplasty. PMID- 27658732 TI - A comparison between the pathophysiology of multiple sclerosis and normal pressure hydrocephalus: is pulse wave encephalopathy a component of MS? AB - BACKGROUND: It has been suggested there is a chronic neurodegenerative disorder, underlying the pathophysiology of multiple sclerosis (MS), which is distinct from the more obvious immune-mediated attack on the white matter. Limited data exists indicating there is an alteration in pulse wave propagation within the craniospinal cavity in MS, similar to the findings in normal pressure hydrocephalus (NPH). It is hypothesized MS may harbor pulse wave encephalopathy. The purpose of this study is to compare blood flow and pulse wave measurements in MS patients with a cohort of NPH patients and control subjects, to test this hypothesis. METHODS: Twenty patients with MS underwent magnetic resonance (MR) flow quantification techniques. Mean blood flow and stroke volume were measured in the arterial inflow and venous out flow from the sagittal (SSS) and straight sinus (ST). The arteriovenous delay (AVD) was defined. The results were compared with both age-matched controls and NPH patients. RESULTS: In MS there was a 35 % reduction in arteriovenous delay and a 5 % reduction in the percentage of the arterial inflow returning via the sagittal sinus compared to age matched controls. There was an alteration in pulse wave propagation, with a 26 % increase in arterial stroke volume but 30 % reduction in SSS and ST stroke volume. The AVD and blood flow changes were in the same direction to those of NPH patients. CONCLUSIONS: There are blood flow and pulsation propagation changes in MS patients which are similar to those of NPH patients. The findings would be consistent with an underlying pulse wave encephalopathy component in MS. PMID- 27658734 TI - Direct correlation of structural and electrical properties of electron-doped individual VO2 nanowires on devised TEM grids. AB - Nano-scale VO2 wires with controlled parameters such as electron-doping have attracted intense interest due to their capability of suppressing the temperature of the metal-insulator transition (MIT). However, because their diameters are smaller than the spatial resolutions of the conventional measuring equipment, the ability to perform a thorough examination of the wires has been hindered. Here, we report the fabrication of a transmission electron microscopy (TEM) grid with an optimum design of Si3N4 windows on which the photolithography for individual electron-doped VO2 nanowire devices can be safely accomplished, allowing the cross-examination of the structural and electrical properties. TEM dark-field imaging was used to quantitatively investigate the fractions of rutile and M1 phases, and their lattice alignments were observed using high-resolution TEM (HRTEM) with small area diffraction. Moreover, electron energy loss spectroscopy (EELS) revealed that the rutile domain would be created by the strain induced by oxygen vacancies. Importantly, we successfully tuned the transition temperature by changing the rutile fraction while maintaining a high level of resistivity change. The resistivity at room temperature linearly decreased with the rutile fraction, following a simple model. Furthermore, the T dependence of the threshold voltage can be attributed to the Joule heating, exhibiting an identical thermal dependence, irrespective of the rutile fraction. PMID- 27658735 TI - Minimal residual disease evaluation in autologous stem cell transplantation recipients with multiple myeloma. PMID- 27658736 TI - Bacterial Abscess Formation Is Controlled by the Stringent Stress Response and Can Be Targeted Therapeutically. AB - Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model. To pharmacologically confirm the role of the stringent response in abscess formation, a cationic peptide that causes rapid degradation of the stringent response mediator, guanosine tetraphosphate (ppGpp), was employed. The therapeutic application of this peptide strongly inhibited lesion formation in mice infected with Gram-positive MRSA and Gram-negative Pseudomonas aeruginosa. Overall, we provide insights into the mechanisms governing abscess formation and a paradigm for treating multidrug resistant cutaneous abscesses. PMID- 27658737 TI - Zika Virus Replicons for Drug Discovery. AB - The current epidemic of Zika virus (ZIKV) has underscored the urgency to establish experimental systems for studying viral replication and pathogenesis, and countermeasure development. Here we report two ZIKV replicon systems: a luciferase replicon that can differentiate between viral translation and RNA synthesis; and a stable luciferase replicon carrying cell line that can be used to screen and characterize inhibitors of viral replication. The transient replicon was used to evaluate the effect of an NS5 polymerase mutation on viral RNA synthesis and to analyze a known ZIKV inhibitor. The replicon cell line was developed into a 96-well format for antiviral testing. Compare with virus infection-based assay, the replicon cell line allows antiviral screening without using infectious virus. Collectively, the replicon systems have provided critical tools for both basic and translational research. PMID- 27658738 TI - The State of Vaccine Confidence 2016: Global Insights Through a 67-Country Survey. AB - BACKGROUND: Public trust in immunization is an increasingly important global health issue. Losses in confidence in vaccines and immunization programmes can lead to vaccine reluctance and refusal, risking disease outbreaks and challenging immunization goals in high- and low-income settings. National and international immunization stakeholders have called for better monitoring of vaccine confidence to identify emerging concerns before they evolve into vaccine confidence crises. METHODS: We perform a large-scale, data-driven study on worldwide attitudes to immunizations. This survey - which we believe represents the largest survey on confidence in immunization to date - examines perceptions of vaccine importance, safety, effectiveness, and religious compatibility among 65,819 individuals across 67 countries. Hierarchical models are employed to probe relationships between individual- and country-level socio-economic factors and vaccine attitudes obtained through the four-question, Likert-scale survey. FINDINGS: Overall sentiment towards vaccinations is positive across all 67 countries, however there is wide variability between countries and across world regions. Vaccine-safety related sentiment is particularly negative in the European region, which has seven of the ten least confident countries, with 41% of respondents in France and 36% of respondents in Bosnia & Herzegovina reporting that they disagree that vaccines are safe (compared to a global average of 13%). The oldest age group (65+) and Roman Catholics (amongst all faiths surveyed) are associated with positive views on vaccine sentiment, while the Western Pacific region reported the highest level of religious incompatibility with vaccines. Countries with high levels of schooling and good access to health services are associated with lower rates of positive sentiment, pointing to an emerging inverse relationship between vaccine sentiments and socio-economic status. CONCLUSIONS: Regular monitoring of vaccine attitudes - coupled with monitoring of local immunization rates - at the national and sub-national levels can identify populations with declining confidence and acceptance. These populations should be prioritized to further investigate the drivers of negative sentiment and to inform appropriate interventions to prevent adverse public health outcomes. PMID- 27658739 TI - Genetic Association Studies Identify Unanticipated Gene Pathways Influencing Sepsis Outcome. PMID- 27658741 TI - Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction - A comparative study. AB - Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF) beta, and a combination of peroxisome proliferator-activated receptor gamma agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF beta-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjogren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance inducing therapy. PMID- 27658742 TI - QSPR studies for predicting polarity parameter of organic compounds in methanol using support vector machine and enhanced replacement method. AB - In the present work, enhanced replacement method (ERM) and support vector machine (SVM) were used for quantitative structure-property relationship (QSPR) studies of polarity parameter (p) of various organic compounds in methanol in reversed phase liquid chromatography based on molecular descriptors calculated from the optimized structures. Diverse kinds of molecular descriptors were calculated to encode the molecular structures of compounds, such as geometric, thermodynamic, electrostatic and quantum mechanical descriptors. The variable selection method of ERM was employed to select an optimum subset of descriptors. The five descriptors selected using ERM were used as inputs of SVM to predict the polarity parameter of organic compounds in methanol. The coefficient of determination, r2, between experimental and predicted polarity parameters for the prediction set by ERM and SVM were 0.952 and 0.982, respectively. Acceptable results specified that the ERM approach is a very effective method for variable selection and the predictive aptitude of the SVM model is superior to those obtained by ERM. The obtained results demonstrate that SVM can be used as a substitute influential modeling tool for QSPR studies. PMID- 27658740 TI - Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study. AB - BACKGROUND: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular repair. EPCs may be reduced in HIV-infected (HIV+) persons, contributing to cardiovascular disease (CVD). Telmisartan is an angiotensin receptor blocker that increases EPCs in HIV-uninfected adults. OBJECTIVE: To assess telmisartan's effects on EPC number and immunophenotype in older HIV + adults at risk for CVD. METHODS: HIV + persons >=50 years old with HIV-1 RNA < 50 copies/mL on suppressive antiretroviral therapy and >=1 CVD risk factor participated in a prospective, open-label, pilot study of oral telmisartan 80 mg daily for 12 weeks. Using CD34 and CD133 as markers of early maturity and KDR as a marker of endothelial lineage commitment, EPCs were quantified via flow cytometry and defined as viable CD3-/CD33-/CD19-/glycophorin- cells of four immunophenotypes: CD133+/KDR+, CD34+/KDR+, CD34+/CD133+, or CD34+/KDR+/CD133+. The primary endpoint was a 12-week change in EPC subsets (NCT01578772). RESULTS: Seventeen participants (88% men, median age 60 years and peripheral CD4+ T lymphocyte count 625 cells/mm3) enrolled and completed the study. After 6 and 12 weeks of telmisartan, frequencies of all EPC immunophenotypes were higher than baseline (all p < 0.10 except week 12 CD133+/KDR+ EPC, p = 0.13). Participants with lower baseline EPC levels had the largest gains. Additionally, the percentage of CD34+ cells with endothelial commitment (KDR+) increased. CONCLUSIONS: Our data suggest that telmisartan use is associated with an increase in circulating EPCs in older HIV + individuals with CVD risk factors. Further controlled studies are needed to assess whether EPC increases translate to a reduction in CVD risk in this population. PMID- 27658743 TI - Thioredoxin-mimetic peptides (TXM) inhibit inflammatory pathways associated with high-glucose and oxidative stress. AB - Impaired insulin signaling and the associated insulin-resistance in liver, adipose tissue, and skeletal muscle, represents a hallmark of the pathogenesis of type 2-diabetes-mellitus. Here we show that in the liver of db/db mice, a murine model of obesity, type 2 diabetes, and dyslipidemia, the elevated activities of mitogen-activated protein kinases (MAPK; ERK1/2 and p38MAPK), and Akt/PKB are abolished by rosiglitazone-treatment, which normalizes blood glucose in db/db mice. This is unequivocal evidence of a functional link between the activation of the MAPK specific inflammatory-pathway and high-blood sugar. A similar reduction in ERK1/2, p38MAPK, and Akt activities but without affecting blood-glucose was observed in the liver of db/db mice treated with a molecule that mimics the action of thioredoxin, called thioredoxin-mimetic peptide (TXM). N-Acetyl-Cys-Pro Cys-amide (TXM-CB3) is a free radical scavenger, a reducing and denitrosylating reagent that protects the cells from early death induced by inflammatory pathways. TXM-CB3 also lowered MAPK signaling activated by the disruption of the thioredoxin-reductase-thioredoxin (Trx-TrxR) redox-system and restored Akt activity in rat hepatoma FAO cells. Similarly, two other TXM-peptides, N-Acetyl Cys-Met-Lys-Cys-amide (TXM-CB13; DY70), and N-Acetyl-Cys-gammaGlu-Cys-Cys-amide (TXM-CB16; DY71), lowered insulin- and oxidative stress-induced ERK1/2 activation, and rescued HepG2 cells from cell death. The potential impact of TXM peptides on inhibiting inflammatory pathways associated with high-glucose could be effective in reversing low-grade inflammation. TXM-peptides might also have the potential to improve insulin resistance by protecting from posttranslational modifications like nitrosylation. PMID- 27658744 TI - Parturition induction in ewes by a progesterone receptor blocker, aglepristone, and subsequent neonatal survival: Preliminary results. AB - The clinical effects of aglepristone treatment to induce parturition in ewes and their newborns were reported. Three experimental groups were defined: group AG5 (n = 5), group AG10 (n = 5), and group CG (n = 5) in which ewes were injected twice with 5, 10 mg/kg of aglepristone, and saline solution of ewes, respectively. Different parameters associated with parturition in ewes and their newborns were investigated. Serum progesterone, oxytocin, and free and conjugated total estrogens were measured after treatments until parturition. No statistical difference was found from first aglepristone administration to onset of lambing between AG5 and AG10 (23.90 +/- 6.20, 40.00 +/- 6.71 hours). Parturition induction in two groups shortened the gestational length significantly compared with the control group (P = 0.003). Dystocia was observed in two ewes in group AG10. The placental weight showed statistically significant difference only between the AG10 and CG (P = 0.039), but no difference was observed in the placental expulsion period between the groups. Decrease in food consumption 24 to 36 hours after parturition in all ewes and skin necrosis in an ewe in group AG5 were observed. Progesterone concentration was significantly lower in AG5 than that in ewes in group AG10 and CG (P < 0.05). No difference was observed in concentrations of free total estrogens and oxytocin between groups. The body temperature of lambs was significantly different between AG10 and CG groups both right after (P = 0.011) and 12 hours after parturition (P = 0.014). The lambs in CG had the highest mean birth weight (4.29 +/- 0.28 kg), which was significantly different from the induced groups. No significant difference of blood pH and blood gases values between groups was identified both at birth and 12 hours after parturition for lambs. Significant differences could clearly be observed in total protein and blood urea nitrogen and total protein findings 12 hours after parturition (P < 0.05), whereas no difference was found in blood glucose, albumin, inorganic phosphor, triglyceride, or total cholesterol parameters. The results of this study show that the administration of aglepristone to induce parturition can precisely control lambing time without any side effects in either mothers or lambs. PMID- 27658745 TI - Semen evaluation and fertility assessment in a purebred dog breeding facility. AB - Semen quality in dogs has not been assessed in a longitudinal study that includes endpoints of female fertility and pregnancy. Although use of artificial insemination with chilled semen is increasingly used in canine reproduction, the resultant level of predictability and odds of fertile matings for dogs is still not fully understood. This research provides, for the first time, comprehensive semen evaluation in a large population of dogs in which fertility has been tracked. Duplicate ejaculates were obtained from 39 Labrador retriever males of the Guide Dogs for the Blind (San Rafael, CA, USA) breeding program. Sperm endpoints were determined in fresh semen and extended chilled semen at 48 hour after collection. Evaluation included total and progressive motility, average path velocity, morphology, membrane lipid peroxidation, presence of sperm reactive oxygen species, sperm chromatin structure, and mitochondrial DNA copy number. Male age ranged from 1 to 10 years and were grouped as young (Y; 1-3 years, n = 21), middle aged (M; 4-6 years, n = 13), and senior (S; 7 years or greater, n = 5) for analysis. The effects of age and sperm state (fresh vs. chilled) on the above sperm endpoints were determined using a linear mixed effects model. Semen endpoint values for all parameters were established for this group of fertile males. Progressive motility was only lower in the senior male chilled samples compared to all other groups, fresh and chilled (P < 0.05). Velocity decreased with increasing age and was lower overall in chilled samples (P < 0.05). Percent morphologically normal sperm was lower in senior dogs compared with the other age groups (P < 0.05). The presence of reactive oxygen species was lower in chilled samples compared with fresh (P < 0.05). For sperm chromatin structure, the senior-aged group had a higher %COMPalphat than the middle-aged group (P < 0.05). Bayesian analysis determined that no differences were seen in total motility, membrane lipid peroxidation, and mitochondrial DNA copy number, with regard to conception rate or average litter size between age groups or between fresh and chilled samples. We observed no effects from semen quality on fertility or fecundity regardless of age, despite the differences found in semen quality. The use of advanced laboratory tests to evaluate sperm parameters beyond the standard motility, morphology, and concentration will open investigation to more specific and sensitive fertility tests in canine reproduction. PMID- 27658746 TI - Site of PGF2alpha injection does not alter effectiveness of the Select Synch + controlled internal drug release and timed artificial insemination protocol. AB - Beef Quality Assurance programs have contributed to significant improvements in the wholesomeness of beef available for consumption. Injection site blemishes in the round have declined since the promotion of administering intramuscular injections in the neck. Unfortunately, many producers continue to administer estrus synchronization (ES) drugs in the rump. The objective of this study was to compare the effectiveness of injection site of PGF2alpha, in ES protocols, on steroid hormone concentrations and pregnancy rates. A Select Synch + 7-day controlled internal drug release ES protocol was conducted with the site of PGF2alpha injection alternated between neck and rump in beef cattle (n = 312) at the Ohio State University Agricultural Technical Institute and North Carolina State University. Blood samples (n = 75) were collected at controlled internal drug release insertion and at the time of artificial insemination (AI) to determine if progesterone (P4) and estrogen (E2) concentrations varied due to PGF2alpha injection site. All cattle were confirmed pregnant by ultrasonography at approximately 30 and 90 days after insemination in North Carolina and approximately 70 days after insemination in Ohio. Data were analyzed as randomized complete block designs in PROC GLIMMIX with animal as the experimental unit. Differences were declared significant at P < 0.05. Site of PGF2alpha injection, in either the neck or rump, did not affect (P > 0.05) overall conception rates in response to AI (58.4% and 55.6%, respectively). Altering PGF2alpha injection site did not impact P4, E2 concentrations, or the P4:E2 ratio at AI (P > 0.05). However, cattle inseminated after displaying estrus had greater (P < 0.05) pregnancy rates than timed AI (67.8 vs. 47.5%, respectively). First service conception rates and pregnancy rates were consistent with previous reports. Overall, altering the location of the PGF2alpha injection during ES did not change circulating hormone concentrations at AI or pregnancy rates; therefore, cattle producers should follow Beef Quality Assurance guidelines when administering ES protocols. PMID- 27658747 TI - Avoiding hemodynamic collapse during high-risk percutaneous coronary intervention: Advanced hemodynamics of impella support. AB - The rate of performing primary percutaneous coronary intervention in patients with complex coronary artery disease is increasing. The use of percutaneous mechanical circulatory support devices provides critical periprocedural hemodynamic support. Mechanical support has increased the safety and efficacy of interventional procedures in this high-risk patient population. Predicting patient response to the selected intervention can be clinically challenging. Here we demonstrate a case where complete hemodynamic collapse during PCI was avoided by mechanical support provided by the Impella device. Further, we employ a comprehensive cardiovascular model to predict ventricular function and patient hemodynamics in response to the procedure. New computational tools may help interventionists visualize, understand, and predict the multifaceted hemodynamic aspects of these high risk procedures in individual patients. (c) 2016 Wiley Periodicals, Inc. PMID- 27658748 TI - Fluid Reasoning Mediates the Association of Birth Weight With ADHD Symptoms in Youth From Multiplex Families With ADHD. AB - OBJECTIVE: We tested mediation of birth weight and ADHD symptoms by multiple biologically plausible neurocognitive functions and evaluated familiality of observed indirect effects. METHOD: 647 youth from 284 multiplex families with ADHD completed the Arithmetic, Digit Span, Vocabulary, and Block Design subtests of the Wechsler Intelligence Scale for Children (WISC). Multiple mediation tested WISC subtests as mediators of birth weight and multi-informant ADHD symptoms. Familiality of indirect effects was estimated via moderated mediation comparing conditional indirect effects across siblings concordant and discordant for ADHD. RESULTS: Controlling for IQ and demographic factors, Arithmetic uniquely mediated birth weight and ADHD symptoms. Conditional indirect effects through Arithmetic did not differ across ADHD concordant and discordant siblings. CONCLUSION: These cross-sectional findings support previous prospective longitudinal research implicating Arithmetic (i.e., fluid reasoning) as a preliminary causal mediator of birth weight and ADHD symptoms, and suggest that this pathway is independent of genetic influences on ADHD. PMID- 27658749 TI - Are people who have a better smell sense, more affected from satiation? AB - INTRODUCTION: The olfactory system is affected by the nutritional balance and chemical state of the body, serving as an internal sensor. All bodily functions are affected by energy loss, including olfaction; hunger can alter odour perception. OBJECTIVE: In this study, we investigated the effect of fasting on olfactory perception in humans, and also assessed perceptual changes during satiation. METHODS: The "Sniffin' Sticks" olfactory test was applied after 16h of fasting, and again at least 1h after Ramadan supper during periods of satiation. All participants were informed about the study procedure and provided informed consent. The study protocol was approved by the local Ethics Committee of Gaziosmanpasa Taksim Education and Research Hospital (09/07/2014 no: 60). The study was conducted in accordance with the basic principles of the Declaration of Helsinki. RESULTS: This prospective study included 48 subjects (20 males, 28 females) with a mean age of 33.6+/-9.7 (range 20-72) years; their mean height was 169.1+/-7.6 (range 150.0-185.0)cm, mean weight was 71.2+/-17.6 (range 50.0 85.0)kg, and average BMI was 24.8+/-5.3 (range 19.5-55.9). Scores were higher on all items pertaining to olfactory identification, thresholds and discrimination during fasting vs. satiation (p<0.05). Identification (I) results: Identification scores were significantly higher during the fasting (median=14.0) vs. satiation period (median=13.0). Threshold (T) results: Threshold scores were significantly higher during the fasting (median=7.3) vs. satiation period (median=6.2). Discrimination (D) results: Discrimination scores were significantly higher during the fasting (median=14.0) vs. satiation period (median=13.0). The total TDI scores were 35.2 (fasting) vs. 32.6 (satiation). When we compared fasting threshold value of >9 and <=9, the gap between the fasting and satiety thresholds was significantly greater in >9 (p<0.05). CONCLUSION: Olfactory function improved during fasting and declined during satiation. The olfactory system is more sensitive, and more reactive to odours, under starvation conditions, and is characterised by reduced activity during satiation. This situation was more pronounced in patients with a better sense of smell. Olfaction-related neurotransmitters should be the target of further study. PMID- 27658750 TI - Exenatide substantially improves proinsulin conversion and cell survival that augment Ins2+/Akita beta cell function. AB - Proinsulin folding imperfections cause extensive beta-cell defects known in diabetes. Here, we investigated whether exenatide can alleviate such defects in proinsulin conversion, beta-cell survival, and insulin secretion, in the Ins2+/Akita beta-cells that have a spontaneous mutation (Cys 96 Tyr) in the insulin 2 gene caused dominant negative misfolding problem. 15 or 120 min exenatide administration substantially improves glucose-stimulated insulin secretion, marked in the secreted insulin levels and proinsulin/insulin ratio. This improvement is mainly due to enhanced conversion of proinsulin to insulin, having nothing to do with the prohormone convertase PC1/3 and PC2 levels. The 15 min improvement is calcium-independent. The 120 min improvement is linked to calcium and/or cAMP dependent mechanisms. This efficacy is validated during longer treatment and in Akita islets. Exenatide improves Ins2+/Akita beta-cell survival and Akita mouse's glucose tolerance. The results suggest a potential of incretin mimetics in alleviating defective proinsulin conversion and other proinsulin misfolding consequences. PMID- 27658751 TI - Does Exposure to Diagnostic Ultrasound Modulate Human Nerve Responses to Magnetic Stimulation? AB - Ultrasound (US) at diagnostic frequency and power is known to alter nerve potentials; however, the precise mechanism of action is unknown. We investigated whether US alters resting nerve potential to lower the threshold for magnetic nerve stimulation. Seventeen healthy subjects were recruited. For each subject, a 1.5 MHz US imaging probe was placed onto the elbow with the beam directed at the ulnar nerve. The probe was coupled to the skin using standard acoustic coupling gel as would be done for a routine clinical US scan. Ulnar nerve stimulation was performed simultaneously with magnetic stimulation (MS). Successful magnetic stimulation of the ulnar nerve was confirmed with nerve potentials measured by electromyography. There was no significant change in electromyography signal when MS was performed during US exposure. US at the diagnostic frequency and power tested does not alter nerve thresholds with MS. Testing at other frequencies is required, however, before US is negated as a technique to modify MS thresholds. PMID- 27658753 TI - Effect of Background Parenchymal Enhancement on Pre-Operative Breast Magnetic Resonance Imaging: How It Affects Interpretation and the Role of Second-Look Ultrasound in Patient Management. AB - Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may either obscure or mimic malignancy. We evaluated the impact of BPE on the diagnostic performance of pre-operative MRI in breast cancer patients, and how second-look ultrasound (US) can help in guiding patient management. Two hundred fifty-three breast cancer patients with pre-operative MRI were included. In moderate or marked BPE, abnormal interpretation rate (38.9% vs. 12.2%) and biopsy rate (27.8% vs. 8.3%) were higher, and specificity (64.7% vs. 89.8%) was lower, compared with minimal or mild BPE (all p < 0.001). Visibility of MRI detected additional suspicious lesions on second-look US did not differ between the two groups (86.7% in minimal or mild BPE vs. 77.1% in moderate or marked BPE, p = 0.296). Increased BPE was related to increased abnormal interpretation rate, additional biopsy rate and decreased specificity. Second-look US was useful in visualization of MRI-detected additional suspicious lesions, regardless of BPE. PMID- 27658752 TI - Comparison of Ultrasound, Pathologic and Prognostic Characteristics of the Follicular Variant of Papillary Thyroid Cancer According to Fine-Needle Aspiration Cytology. AB - The aim of the study described here was to compare ultrasound features, pathologic characteristics and prognoses of the follicular variant of papillary thyroid carcinoma (FVPTC) according to cytology results. Eighty-seven FVPTCs were classified according to the first cytology results as the surgery group (n = 66, follicular neoplasm/Hurthle cell neoplasm, suspicious for malignancy and malignancy) and the indeterminate group (n = 21, non-diagnostic and benign), for whom the management was follow-up. The indeterminate group had a longer mean interval to surgery (p = 0.020) and larger tumor size (p = 0.018). More tumors were assessed as probably benign in the indeterminate group than in the surgery group (p < 0.001). Extrathyroidal extension and lymph node metastasis did not significantly differ between the two groups, and no patient had a recurrence (mean follow-up interval: 54.9 +/- 16.9 mo). The indeterminate group exhibited more probably benign features and larger size on ultrasound, with surgery being performed at a later date. However, aggressive pathologic characteristics and tumor recurrence did not significantly differ between the two groups. PMID- 27658754 TI - Increased levels of HMGB1 in trophoblastic debris may contribute to preeclampsia. AB - Preeclampsia is triggered by an as yet unknown toxin from the placenta. Antiphospholipid antibodies (aPL), a strong risk factor for preeclampsia, have been shown to induce the production of toxic trophoblastic debris from the placenta. High mobility group box 1 (HMGB1) is a proinflammatory danger signal, and the expression of it has been reported to be increased in preeclampsia. This study examined whether aPL or preeclamptic sera increase the expression of HMGB1 in the syncytiotrophoblast or trophoblastic debris. Trophoblastic debris from normal placental explants that had been cultured with aPL or preeclamptic sera was exposed to endothelial cells. Endothelial cell activation was quantified by cell-surface ICAM-1 expression and U937 monocyte adhesion. The expression of HMGB1 in placental explants and trophoblastic debris that had been treated with aPL or preeclamptic sera was measured by immunohistochemistry and western blotting. The expression of the receptor for advanced glycation end products (RAGE) in endothelial cells was quantified by western blotting. Compared with controls, the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast and trophoblastic debris was increased by treating placental explants with aPL or preeclamptic sera. The increased levels of HMGB1 contributed to endothelial cell activation, mediated in part by the RAGE. Preeclamptic sera and aPL both induced an increase in the cytoplasmic levels of the danger signal HMGB1 in trophoblastic debris. This increased HMGB1 in trophoblastic debris may be one of the toxic factors released from the placenta in preeclampsia. PMID- 27658755 TI - A comparative study of different surgical methods in the treatment of traumatic temporomandibular joint ankylosis. AB - Two different surgical methods for the treatment of unilateral traumatic temporomandibular joint (TMJ) ankylosis with a medially displaced residual condyle are described. Eighteen patients with unilateral traumatic TMJ ankylosis and a medially displaced residual condyle, treated between 2008 and 2013, were included in this study. Group A patients (n=10) were treated with an autogenous coronoid process graft (ACPG) for reconstruction of the mandibular condyle, while group B patients (n=8) were treated by lateral arthroplasty (LAP); a temporalis myofascial flap (TMF) was used as interpositional material in both groups. The long-term results of the two treatments were compared through postoperative computed tomography and clinical follow-up examinations. The two groups were compared in terms of the recurrence rate, facial pattern change, and improvement in maximum inter-incisal opening (MIO) using SPSS 18.0 software. All patients were followed up for 12-24 months. Two patients in group A (20%) had reankylosis; no reankylosis was observed in group B patients. Compared with the ACPG, LAP improved the facial pattern and MIO significantly (P<0.05). LAP is a feasible and effective surgical method for the treatment of unilateral traumatic TMJ ankylosis when the displaced residual condyle is bigger than one third of the condylar head. PMID- 27658756 TI - Treating Smokers in Substance Treatment With Contingent Vouchers, Nicotine Replacement and Brief Advice Adapted for Sobriety Settings. AB - : Treatment for substance use disorders (SUD) provides an opportunity to use voucher-based treatment for smoking. Nicotine replacement (NRT) could improve outcomes previously observed with vouchers without NRT. METHODS: A randomized controlled trial compared contingent vouchers (CV) for smoking abstinence to noncontingent vouchers (NV), when all received counseling and NRT. Smokers who had not sought smoking treatment (n=340) in residential SUD treatment were provided 14days of vouchers for complete smoking abstinence per exhaled carbon monoxide (CO) after a 5-day smoking reduction period, or vouchers only for breath samples, plus brief advice (four sessions) and 8weeks of NRT. RESULTS: Within treatment, 20% had complete abstinence with CV, 5% with NV (p<.001), and participants showed 50% of days abstinent in CV compared to 22% in NV (p<.001). Across 1, 3, 6 and 12months after randomization, CV resulted in significantly fewer cigarettes per day (p<.01) and fewer days smoking (p<.01), but with small effects. Point-prevalence abstinence differences across follow-up (e.g., 4% CV, 2% in NV at 6 and 12months) were not significant. No differences in substance use were seen. CONCLUSIONS: Within-treatment effects on abstinence are stronger than in a prior study of the same CV with BA but without NRT, but NRT does not improve abstinence after vouchers end. Implications for voucher-based treatment include investigating effects when combined with stronger smoking medications and using motivational interviewing. Smoking treatment does not harm SUD recovery. PMID- 27658757 TI - Blood urea nitrogen-to-creatinine ratio in the general population and in patients with acute heart failure. AB - OBJECTIVE: The blood urea nitrogen-to-creatinine (BUN/creatinine) ratio has been proposed as a useful parameter in acute heart failure (AHF), but data on the normal range and the added value of the ratio compared with its separate components in patients with AHF are lacking. The aim of this study is to define the normal range of BUN/creatinine ratio and to investigate its clinical significance in patients with AHF. METHODS: In 4484 subjects from the general population without cardiovascular comorbidities, we calculated age-specific and sex-specific normal values of the BUN/creatinine ratio, deriving a higher and lower than normal range of BUN/creatinine ratio (exceeding the 95% prediction intervals). Association of abnormal range to prognosis was tested in 2033 patients with AHF for the outcome of all-cause death through 180 days, death or cardiovascular or renal rehospitalisation through 60 days and heart failure (HF) rehospitalisation within 60 days. RESULTS: In a cohort of patients with AHF, 482 (24.6%) and 28 (1.4%) patients with HF were classified into higher and lower than normal range groups, respectively. In Cox regression analysis, higher than normal range of BUN/creatinine ratio group was an independent predictor for all-cause death (HR: 1.86, 95% CI 1.29 to 2.66) and death or cardiovascular or renal rehospitalisation (HR: 1.37, 95% CI 1.03 to 1.82), but not for HF rehospitalisation (HR: 1.23, 95% CI 0.81 to 1.86) after adjustment for other prognostic factors including both creatinine and BUN. CONCLUSIONS: In patients with AHF, BUN/creatinine higher than age-specific and sex-specific normal range is associated with worse prognosis independently from both creatinine and BUN. CLINICAL TRIALS: gov identifier NCT00328692 and NCT00354458. PMID- 27658759 TI - Childhood obesity and asthma: To BMI or not to BMI? PMID- 27658760 TI - High-resolution metabolomics to identify urine biomarkers in corticosteroid resistant asthmatic children. AB - BACKGROUND: Corticosteroid (CS) treatment has been established as the first anti inflammatory treatment for adults and children with asthma. However, a subset of patients fails to respond to combined systemic and inhaled CS treatment. OBJECTIVE: This study was aimed at further understanding CS resistance among children with severe asthma. METHODS: High-resolution metabolomics was performed on urine samples from CS-respondent (n = 15) and CS-nonrespondent (n = 15) children to determine possible urine biomarkers related to CS resistance. The metabolic phenotypes of CS responders and CS nonresponders were analyzed using bioinformatics including Manhattan plot with false- discovery rate, hierarchical cluster analysis, Kyoto Encyclopedia Genes and Genomes, and Mummichog pathway analysis. RESULTS: The 2-way hierarchical cluster analysis study determined 30 metabolites showing significantly different levels between CS responders and CS nonresponders. The important metabolites annotated were 3,6-dihydronicotinic acid (126.05 m/z, RT: 106, [M+H]+), 3-methoxy-4-hydroxyphenyl(ethylene)glycol (185.05 m/z, RT: 155, [M+H]+), 3,4-dihydroxy-phenylalanine (198.07 m/z, RT: 446, [M+H]+), gamma-glutamylcysteine (236.06 m/z, RT: 528, [M+S(34)+H]+), Cys-Gly, (253.06 m/z, RT: 528, [M-NH3+H]+), and reduced Flavin mononucleotide (517.0794 m/z, RT: 533, [M+NaCl]+). Tyrosine metabolism, degradation of aromatic compounds, and glutathione metabolism are suggested to be significant pathways relating to CS resistance. CONCLUSIONS: High-resolution metabolomics is a promising approach in asthma research. Five candidate markers were identified to be related to CS resistant children with severe asthma. These compounds, upon validation, may contribute further in the understanding of CS resistance among children with severe asthma through the use of urine. PMID- 27658758 TI - Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps. AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. OBJECTIVES: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. METHODS: Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. RESULTS: Thirty seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. CONCLUSIONS: SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcepsilonRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcepsilonRI complexes. PMID- 27658761 TI - A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis. AB - BACKGROUND: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. OBJECTIVES: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. METHODS: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. RESULTS: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. CONCLUSIONS: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID. PMID- 27658762 TI - Efficacy and safety of canakinumab in Schnitzler syndrome: A multicenter randomized placebo-controlled study. AB - BACKGROUND: Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available. OBJECTIVE: We assessed effects of the anti IL-1beta mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome. METHODS: In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey). RESULTS: The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension. CONCLUSIONS: In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease. PMID- 27658763 TI - Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge. AB - BACKGROUND: An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis, relates to an intact epithelial/epidermal barrier during early childhood. Conceivably, the immunologic and genomic footprint of this resistance is preserved in nonatopic, nonallergic adults and is unmasked during exposure to an aeroallergen. OBJECTIVE: The aim of this study was to obtain direct support of the epithelial/epidermal barrier model for allergic rhinoconjunctivitis. METHODS: Twenty-three adults allergic to house dust mites (HDMs) (M+) and 15 nonsensitive, nonallergic (M-) participants completed 3-hour exposures to aerosolized HDM (Dermatophagoides pteronyssinus) powder on 4 consecutive days in an allergen challenge chamber. We analyzed: (1) peripheral blood leukocyte levels and immune responses; and (2) RNA sequencing derived expression profiles of nasal cells, before and after HDM exposure. RESULTS: On HDM challenge: (1) only M+ persons developed allergic rhinoconjunctivitis symptoms; and (2) peripheral blood leukocyte levels/responses and gene expression patterns in nasal cells were largely concordant between M+ and M- participants; gross differences in these parameters were not observed at baseline (pre-exposure). Two key differences were observed. First, peripheral blood CD4+ and CD8+ T-cell activation levels initially decreased in M- participants versus increased in M+ participants. Second, in M- compared with M+ participants, genes that promoted epidermal/epithelial barrier function (eg, filament-aggregating protein [filaggrin]) versus inflammation (eg, chemokines) and innate immunity (interferon) were upregulated versus muted, respectively. CONCLUSION: An imprint of resistance to HDM challenge in nonatopic, nonallergic adults was muted T-cell activation in the peripheral blood and inflammatory response in the nasal compartment, coupled with upregulation of genes that promote epidermal/epithelial cell barrier function. PMID- 27658764 TI - Self-Reported Physical Activity Using the International Physical Activity Questionnaire (IPAQ) in Australian Adults with Type 2 Diabetes, with and Without Peripheral Neuropathy. AB - OBJECTIVES: The aim of this study was to survey the level of self-reported physical activity in people with type 2 diabetes, with and without peripheral neuropathy. METHODS: A sample of South Australian adults (n=481) 33 to 88 years of age who had type 2 diabetes, including 55 people with peripheral neuropathy, completed the International Physical Activity Questionnaire (IPAQ). Levels of self-reported physical activity were compared between those with and without peripheral neuropathy. RESULTS: People with type 2 diabetes and peripheral neuropathy (median [Mdn]=1433; interquartile range [IQR]=495 to 3390 metabolic equivalent minutes per week [MET-min/wk]) were less physically active than those without peripheral neuropathy (Mdn=2106; IQR=876 to 4380 MET-min/wk) (p=0.04). A total of 49% of people with type 2 diabetes and peripheral neuropathy met physical activity recommendations of 150 minutes of at least moderate activity per week, compared to 57% of people with type 2 diabetes alone. CONCLUSIONS: These findings demonstrate that people with type 2 diabetes and peripheral neuropathy reported being significantly less active than people with type 2 diabetes alone. People with type 2 diabetes and peripheral neuropathy need to be encouraged to perform higher levels of physical activity for biologic, physical and psychological benefits. Further studies using objective measures of physical activity are required to support these results. PMID- 27658765 TI - The Effect of Nurse Practitioner-Led Intervention in Diabetes Care for Patients Admitted to Cardiology Services. AB - OBJECTIVE: To determine the benefits of diabetes nurse practitioner (DNP) intervention on glycemic control, quality of life and diabetes treatment satisfaction in patients with type 2 diabetes (T2DM) admitted to cardiology inpatient services at a tertiary centre. PATIENTS AND METHODS: Patients admitted to the cardiology service with T2DM who had suboptimal control (HbA1c >6.5%) were approached for the study. Diabetes care was optimized by the DNP through medication review, patient education and discharge care planning. Glycemic control was evaluated with 3-month post-intervention HbA1c. Secondary outcomes of lipid profiles, quality of life and treatment satisfaction were evaluated at baseline and at 3 months with fasting lipids, Audit of Diabetes-Dependent Quality of Life questionnaires (ADDQoL) and Diabetes Treatment Satisfaction Questionnaires (DTSQ) respectively. RESULTS: With almost 49% of patients admitted to the Mazankowski Alberta Heart Institute having HbA1c <6.5%, only 23 patients completed the study over a 12-month period. We found a significant decrease in HbA1c values at 3 months post-intervention from 8.0% (SD=1. 2) to 6.9% (SD=0.7), p=0.002. LDL showed a significant decrease at 3 months from 1.7 mmol/L (SD=0.7) to 1.1 mmol /L (SD=0.6), p=0.011. Overall median ADDQoL impact scores improved at follow up, from -1.4 to -0.4, p = 0.0003. Overall no significant changes in DTSQ scores were seen. CONCLUSIONS: Short-term DNP intervention in T2DM patients admitted to the inpatient cardiology service was associated with benefits in areas of glycemic control and various domains of QoL. Our study provides support for the involvement of DNP in the care of cardiology inpatients at tertiary centres. PMID- 27658766 TI - Diabetes in Emerging Adulthood: Transitions Lost in Translation. PMID- 27658767 TI - Characterization of methicillin-resistant Staphylococcus aureus isolates from fitness centers in the Memphis metropolitan area, Tennessee. AB - Indoor skin-contact surfaces of public fitness centers may serve as reservoirs of potential human transmission of methicillin-resistant Staphylococcus aureus (MRSA). We found a high prevalence of multidrug-resistant (MDR) MRSA of clonal complex 59 lineage harboring a variety of extracellular toxin genes from surface swab samples collected from inanimate surfaces of fitness centers in the Memphis metropolitan area, Tennessee. Our findings underscore the role of inanimate surfaces as potential sources of transmission of MDR MRSA strains with considerable genetic diversity. PMID- 27658768 TI - A novel type of hand hygiene technique. PMID- 27658769 TI - Impact of a hand hygiene campaign in a tertiary hospital in South Korea on the rate of hospital-onset methicillin-resistant Staphylococcus aureus bacteremia and economic evaluation of the campaign. AB - BACKGROUND: Hand hygiene (HH) is the most important factor affecting health care associated infections. METHODS: We introduced a World Health Organization HH campaign in October 2010. The monthly procurement of hand sanitizers per 1,000 patient days was calculated, and the monthly incidence of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), classified into community- and hospital onset (HO), was measured from a microbiologic laboratory database. Trends of MRSAB incidence were assessed using Bayesian structural time series models. A cost-benefit analysis was also performed based on the economic burden of HO MRSAB in Korea. RESULTS: Procurement of hand sanitizers increased 134% after the intervention (95% confidence interval [CI], 120%-149%), compared with the preintervention period (January 2008-September 2010). In the same manner, HH compliance improved from 33.2% in September 2010 to 92.2% after the intervention. The incidence of HO MRSAB per 100,000 patient days decreased 33% (95% CI, -57% to -7.8%) after the intervention. Because there was a calculated reduction of 65 HO MRSAB cases during the intervention period, the benefit outweighed the cost (total benefit [$851,565]/total cost [$167,495] = 5.08). CONCLUSIONS: Implementation of the HH campaign led to increased compliance and significantly reduced HO MRSAB incidence; it was also cost saving. PMID- 27658770 TI - What parents think and feel about deep brain stimulation in paediatric secondary dystonia including cerebral palsy: A qualitative study of parental decision making. AB - BACKGROUND: Dystonia is characterised by involuntary movements and postures. Deep Brain Stimulation (DBS) is effective in reducing dystonic symptoms in primary dystonia in childhood and to lesser extent in secondary dystonia. How families and children decide to choose DBS surgery has never been explored. AIMS: To explore parental decision-making for DBS in paediatric secondary dystonia. METHODS: Data was gathered using semi-structured interviews with eight parents of children with secondary dystonia who had undergone DBS. Interviews were analysed using Interpretative Phenomenological Analysis. RESULTS: For all parents the decision was viewed as significant, with life altering consequences for the child. These results suggested that parents were motivated by a hope for a better life and parental duty. This was weighed against consideration of risks, what the child had to lose, and uncertainty of DBS outcome. Decisions were also influenced by the perspectives of their child and professionals. CONCLUSIONS: The decision to undergo DBS was an ongoing process for parents, who ultimately were struggling in the face of uncertainty whilst trying to do their best as parents for their children. These findings have important clinical implications given the growing referrals for consideration of DBS childhood dystonia, and highlights the importance of further quantitative research to fully establish the efficacy of DBS in secondary dystonia to enhance informed decision-making. PMID- 27658771 TI - Current experience of spinal neuromodulation in chronic pain: Is there a role in children and young people? AB - INTRODUCTION: Chronic pain in children has been an under-recognized problem compared to adult pain. The aim of management is to help children and their families cope with the symptoms rather than a cure. Current medical treatments to reduce pain intensity are often short lived, poorly tolerated or ineffective. RESULTS: The use of electrical stimulation to treat pain is the current basis of modern Neuromodulation at the spinal cord and has been well established as spinal cord stimulation in adult practice. This involves placement of an epidural electrode connected to a subcutaneous implanted pulse generator. The electrode generates an electrical field at the dorsal columns of the spinal cord that inhibits pain pathways. Randomised controlled trials have demonstrated efficacy in neuropathic pain states such as the failed back surgery syndrome and complex regional pain syndrome. CONCLUSION: Despite its initial expense, Spinal cord stimulation is a cost effective therapy in the long term and has the advantages of being a minimally invasive therapy and reversible. PMID- 27658772 TI - Estrogen Signals Through Peroxisome Proliferator-Activated Receptor-gamma Coactivator 1alpha to Reduce Oxidative Damage Associated With Diet-Induced Fatty Liver Disease. AB - BACKGROUND & AIMS: Inefficient fatty acid oxidation in mitochondria and increased oxidative damage are features of non-alcoholic fatty liver disease (NAFLD). In rodent models and patients with NAFLD, hepatic expression of peroxisome proliferator-activated receptor-gamma (PPARG) coactivator 1alpha (PPARGC1A or PGC1A) is inversely correlated with liver fat and disease severity. A common polymorphism in this gene (rs8192678, encoding Gly482Ser) has been associated with NAFLD. We investigated whether reduced expression of PGC1A contributes to development of NAFLD using mouse models, primary hepatocytes, and human cell lines. METHODS: HepG2 cells were transfected with variants of PPARGC1A and protein and messenger RNA levels were measured. Mice with liver-specific hemizygous or homozygous disruption of Ppargc1a (Ppargc1af/+Alb-cre+/0 and Ppargc1af/f Alb-cre+/0 mice, respectively) were fed regular chow (control) or a high-fat diet supplemented with 30% d-fructose in drinking water (obesogenic diet) for 25-33 weeks. Liver tissues were analyzed by histology and by immunoblotting. Primary hepatocytes were analyzed for insulin signaling, reactive oxygen species, and estrogen response. Luciferase reporter expression was measured in transfected H2.35 cells expressing an estrogen receptor reporter gene, estrogen receptor 1, and/or PGC1A/B. RESULTS: The serine 482 variant of the human PGC1A protein had a shorter half-life than the glycine 482 variant when expressed in HepG2 cells. Liver tissues from mice with liver-specific hemizygous disruption of Ppargc1a placed on an obesogenic diet expressed increased markers of inflammation and fibrosis and decreased levels of antioxidant enzymes compared with the Ppargc1a+/+ on the same diet. Oxidative damage was observed in livers from Ppargc1af/+Alb-cre+/0 mice of each sex, in a cell-autonomous manner, but was greater in livers from the female mice. Expression of PGC1A in H2.35 cells coactivated estrogen receptor 1 and was required for estrogen-dependent expression of genes that encode antioxidant proteins. These findings could account for the increased liver damage observed in female Ppargc1af/+Alb-cre+/0 mice; while, compensatory increases in PPARG coactivator 1beta could prevent oxidative damage associated with complete loss of PGC1A expression in Ppargc1af/fAlb-cre+/0 female mice. CONCLUSIONS: In mice, loss of estrogen signaling contributes to oxidative damage caused by low levels of PGC1A in liver, exacerbating steatohepatitis associated with diets high in fructose and fat. PMID- 27658773 TI - Profiling of downregulated blood-circulating miR-150-5p as a novel tumor marker for cholangiocarcinoma. AB - Altered microRNA (miRNA) expression plays a role in cholangiocarcinoma (CCA) development; thus, detection of blood-circulating miRNAs could be useful as CCA markers. This study profiled serum miRNA levels in patients with primary sclerosing cholangitis (PSC) and CCA and then assessed the role of miR-150-5p in CCA progression in vitro. Three samples were randomly selected from each of 50 sera of healthy controls, 30 PSC sera, and 28 CCA sera with matched bile samples for miRNA microarray profiling. The dysregulated miRNAs were confirmed using qRT PCR, and miR-150-5p was selected for further in vitro and ex vivo studies. The miRNA microarray identified three dysregulated miRNAs in both CCA and PSC samples, while miR-150-5p level was consistently lower in CCA sera, bile, and tissues than in normal control and PSC sera (P < 0.05). Furthermore, levels of miR-150-5p were associated with serum carbohydrate antigen 19-9 (CA19-9) levels and CCA pathological grade. Bioinformatic Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that miR-150-5p could regulate hand full gene pathways, including cancer pathway (P < 0.01). However, overexpression of miR-150-5p inhibited proliferation, migration, and invasion capability of CCA cells (P < 0.05). Luciferase reporter assay showed that miR-150-5p bound to an oncogene Ets including gene-1 (ELK1), and Western blot data confirmed that miR 150-5p suppressed ELK1 expression in CCA cell lines. These results suggest that reduced miR-150-5p expression could contribute to CCA development and progression due to uncontrolled ELK1 expression. Thus, further study could evaluate miR-150 5p as a novel target and predictor for CCA prevention and treatment. PMID- 27658774 TI - Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression. AB - Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma. PMID- 27658775 TI - Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma. AB - Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. However, the role of IGFBP3 in tumor metastasis remains under debate. Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. Besides, NPC cells stimulated with recombinant IGFBP3 accelerated migration and adhesion. These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target. PMID- 27658776 TI - The mitochondrion interfering compound NPC-26 exerts potent anti-pancreatic cancer cell activity in vitro and in vivo. AB - The development of novel anti-pancreatic cancer agents is extremely important. Here, we investigated the anti-pancreatic cancer activity by NPC-26, a novel mitochondrion interfering compound. We showed that NPC-26 was anti-proliferative and cytotoxic to human pancreatic cancer cells, possibly via inducing caspase-9 dependent cell apoptosis. Pharmacological inhibition or shRNA-mediated silence of caspase-9 attenuated NPC-26-induced pancreatic cancer cell death and apoptosis. Further, NPC-26 treatment led to mitochondrial permeability transition pore (mPTP) opening in the cancer cells, which was evidenced by mitochondrial depolarization, ANT-1(adenine nucleotide translocator-1)-Cyp-D (cyclophilin-D) association and oxidative phosphorylation disturbance. mPTP blockers (cyclosporin and sanglifehrin A) or shRNA-mediated knockdown of key mPTP components (Cyp-D and ANT-1) dramatically attenuated NPC-26-induced pancreatic cancer cell apoptosis. Importantly, we showed that NPC-26, at a low concentration, potentiated gemcitabine-induced mPTP opening and subsequent pancreatic cancer cell apoptosis. In vivo, NPC-26 intraperitoneal injection significantly suppressed the growth of PANC-1 xenograft tumors in nude mice. Meanwhile, NPC-26 sensitized gemcitabine mediated anti-pancreatic cancer activity in vivo. In summary, the results of this study suggest that NPC-26, alone or together with gemcitabine, potently inhibits pancreatic cancer cells possibly via disrupting mitochondrion. PMID- 27658777 TI - Lentivirus-mediated silencing of HSDL2 suppresses cell proliferation in human gliomas. AB - Gliomas are the most common type of malignant brain tumors, and the related prognosis is poor. Though many genes have been identified as factors in the development and progression of gliomas, underlying mechanisms remained unclear. It was clear that abnormal lipid metabolism was one of the major hallmarks of cancers. However, few factors associated with lipid metabolism have been reported to be involved in cancer pathogenesis. Hydroxysteroid dehydrogenase-like 2 (HSDL2) is a protein containing sterol carrier protein 2 (SCP2) domain localized in peroxisomes, which indicated that HSDL2 might be a fatty acid regulatory factor. Here, we revealed that HSDL2 was significantly upregulated in gliomas and its expression was positively correlated with glioma grades. Furthermore, lentiviral-mediated HSDL2 knockdown showed that HSDL2 downregulation inhibited the proliferation in two human glioblastoma cell lines U-251 cells and U87 MG cells, induced cell cycle arrest, and promoted cell apoptosis. Our study provided multiple lines of evidence for the causal relationship between HSDL2 overexpression and glioma progression and provided possible mechanisms underlying HSDL2-mediated glioma growth. Taken together, these results indicated that HSDL2 might serve as a potential target for glioma treatment in the future. PMID- 27658778 TI - The role of ADAM17 in tumorigenesis and progression of breast cancer. AB - A disintegrin and metalloproteinase (ADAM) family members are known to process the target membrane-bound molecules through the quick induction of their protease activities under interaction with other molecules, which have diverse roles in tissue morphogenesis and pathophysiological remodeling. Among these, ADAM17 is a membrane-bound protease that sheds the extracellular domain of various receptors or its ligands from the cell membrane and subsequently activates downstream signaling transduction pathways. Importantly, breast cancer remains a mainspring of cancer-induced death in women, and numerous regulatory pathways have been implicated in the formation of breast cancer. Substantial evidence has demonstrated that an obvious increased in ADAM17 cell surface expression has been discovered in breast cancer and was shown to be associated with mammary tumorigenesis, invasiveness, and drug resistance. Over the last decades, it has received more than its share of attention that ADAM17 plays a potential role in breast cancer, including cell proliferation, invasion, angiogenesis, apoptosis, and trastuzumab resistance. In our review, we discuss the mechanisms through which ADAM17 acts on breast cancer tumorigenesis and progression. Thus, this will provide further impetus for exploiting ADAM17 as a new target for breast cancer treatment. PMID- 27658779 TI - Low expression of DCXR protein indicates a poor prognosis for hepatocellular carcinoma patients. AB - The aim of this study was to investigate the prognostic value of dicarbonyl/L xylulose reductase (DCXR) in human hepatocellular carcinoma (HCC). Immunohistochemistry and tissue microarrays were used to evaluate DCXR protein expression levels. Image-Pro Plus was used to calculate the integral optic density (IOD) in each tissue sample, which represented the expression level of DCXR. DCXR proteins were found to be significantly lower in HCC tumor tissues (P < 0.0001) according to immunohistochemical analysis of DCXR protein levels in 74 paired HCC tissue and peritumoral non-cancer tissues. The prognostic value of DCXR in HCC was assessed in 290 cases of the training cohort and 74 cases of the validation cohort. Shorter overall survival (OS) time and shorter time to recurrence (TTR) in both the training and validation set were found to be associated with lower expression levels of DCXR. In the training set, the expression level of DCXR in HCC was an independent prognostic factor for OS according to univariate and multivariate analyses. In conclusion, DCXR expression is an independent prognostic factor for OS and TTR of post-operative HCC patients, and low expression levels of DCXR in HCC may indicate poor outcome of HCC patients after surgical resection. PMID- 27658780 TI - HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma. AB - Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors. PMID- 27658781 TI - Hepatitis B virus X protein in liver tumor microenvironment. AB - Encoded by the hepatitis B virus, hepatitis B virus X protein (HBx) is a multifunctional, potentially oncogenic protein that acts primarily during the progression from chronic hepatitis B to cirrhosis and hepatocellular carcinoma (HCC). In recent decades, it has been established that chronic inflammation generates a tumor-supporting microenvironment. HCC is a typical chronic inflammation-related cancer, and inflammation is the main risk factor for HCC progression. The viral transactivator HBx plays a pivotal role in the initiation and maintenance of hepatic inflammatory processes through interactions with components of the tumor microenvironment including tumor cells and the surrounding peritumoral stroma. The complex interactions between HBx and this microenvironment are thought to regulate tumor growth, progression, invasion, metastasis, and angiogenesis. In this review, we have summarized the current evidence evaluating the function of HBx and its contribution to the inflammatory liver tumor microenvironment. PMID- 27658783 TI - Strigolactones redefine plant hormones. PMID- 27658782 TI - Systematic procedure for identifying the five main ossification stages of the medial clavicular epiphysis using computed tomography: a practical proposal for forensic age diagnostics. AB - In forensic age estimations of living individuals, computed tomography of the clavicle is widely used for determining the age of majority. To this end, the degree of ossification of the medial clavicular epiphysis can be determined by means of two classification systems complementing each other: a 5-stage system and an additional 6-stage system that further sub-classifies the stages 2 and 3. In recent years, practical experience and new data revealed that difficulties and even wrong stage determinations may occur especially when following the short descriptions of the fundamental 5-stage system only. Based on current literature, this article provides a systematic procedure for identifying the five main ossification stages by listing important preconditions and presenting an algorithm that is comprised of four specific questions. Each question is accompanied by comprehensive and detailed descriptions which specify the criteria used for differentiation. The information is subdivided into "single-slice view" and "multi-slice view." In addition, illustrative case examples and schematic drawings facilitate application of the procedure in forensic practice. The pitfalls associated with the criteria of stage determination will be discussed in detail. Eventually, two general rules will be inferred to assign correct ossification stages of the medial clavicular epiphysis by means of computed tomography. PMID- 27658785 TI - Mitochondrial dynamics during cell cycling. AB - Mitochondria are the cell's power plant that must be in a proper functional state in order to produce the energy necessary for basic cellular functions, such as proliferation. Mitochondria are 'dynamic' in that they are constantly undergoing fission and fusion to remain in a functional state throughout the cell cycle, as well as during other vital processes such as energy supply, cellular respiration and programmed cell death. The mitochondrial fission/fusion machinery is involved in generating young mitochondria, while eliminating old, damaged and non repairable ones. As a result, the organelles change in shape, size and number throughout the cell cycle. Such precise and accurate balance is maintained by the cytoskeletal transporting system via microtubules, which deliver the mitochondrion from one location to another. During the gap phases G1 and G2, mitochondria form an interconnected network, whereas in mitosis and S-phase fragmentation of the mitochondrial network will take place. However, such balance is lost during neoplastic transformation and autoimmune disorders. Several proteins, such as Drp1, Fis1, Kif-family proteins, Opa1, Bax and mitofusins change in activity and might link the mitochondrial fission/fusion events with processes such as alteration of mitochondrial membrane potential, apoptosis, necrosis, cell cycle arrest, and malignant growth. All this indicates how vital proper functioning of mitochondria is in maintaining cell integrity and preventing carcinogenesis. PMID- 27658784 TI - The ROS derived mitochondrial respirstion not from NADPH oxidase plays key role in Celastrol against angiotensin II-mediated HepG2 cell proliferation. AB - Angiotensin II (AngII) is an important factor that promotes the proliferation of cancer cells, whereas celastrol exhibits a significant antitumor activity in various cancer models. Whether celastrol can effectively suppress AngII mediated cell proliferation remains unknown. In this study, we studied the effect of celastrol on AngII-induced HepG2 cell proliferation and evaluated its underlying mechanism. The results revealed that AngII was able to significantly promote HepG2 cell proliferation via up-regulating AngII type 1 (AT1) receptor expression, improving mitochondrial respiratory function, enhancing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, increasing the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines. The excess ROS from mitochondrial dysfunction is able to cause the apoptosis of tumor cells via activating caspase3 signal pathway. In addition, the reaction between NO and ROS results in the formation of peroxynitrite (ONOO-), and then promoting cell damage. celastrol dramatically enhanced ROS generation, thereby causing cell apoptosis through inhibiting mitochodrial respiratory function and boosting the expression levels of AngII type 2 (AT2) receptor without influencing NADPH oxidase activity. PD123319 as a special inhibitor of AT2R was able to effectively decreased the levels of inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activity, but only partially attenuate the effect of celastrol on AnII mediated HepG2 cell proliferation. Thus, celastrol has the potential for use in liver cancer therapy. ROS derived from mitochondrial is an important factor for celastrol to suppress HepG2 cell proliferation. PMID- 27658787 TI - Tumor like reversible seizure-induced brain MRI abnormalities in a patient previously treated for Nocardia brain abscess. An avoided clinical pitfall. PMID- 27658788 TI - Linking cognitive abilities with the propensity for risk-taking: the balloon analogue risk task. AB - There is great interest about the individual differences that influence the ability of dealing with risky decisions. In this light, an intriguing question is whether decision-making during risk is related to other cognitive abilities, especially executive functions. To investigate, in healthy subjects, the existence of a possible correlation between risk-taking and cognitive abilities, the balloon analogue risk task (BART) has been exploited to assess risk-taking propensity and the random number generation (RNG), to investigate cognitive functions. The risk-taking propensity is significantly correlated with the Cycling factor, a feature of RNG performance specifically related to the ability of updating and monitoring information. In particular, an excessive activity of monitoring (expressed by lower values of Cycling factor) is related to a more risk-averse behavior. An overlapping between the circuits involved in both RNG and BART, centered on the dorsolateral prefrontal cortex, could be the possible neurophysiological substrate for this correlation. This study suggests a relevant contribution of executive functions in risk-taking behavior. This could have relevant implications in neuroeconomics and neuropsychiatry of addiction and pathological gambling. PMID- 27658786 TI - An Eye on Age-Related Macular Degeneration: The Role of MicroRNAs in Disease Pathology. AB - Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries, and is the third leading cause worldwide. Emerging evidence suggests that beside environmental and genetic factors, epigenetic mechanisms, such as microRNA (miRNA) regulation of gene expression, are relevant to AMD providing an exciting new avenue for research and therapy. MiRNAs are short, non coding RNAs thought to be imperative for coping with cellular stress. Numerous studies have analyzed miRNA dysregulation in AMD patients, although with varying outcomes. Four studies which profiled dysregulated circulating miRNAs in AMD yielded unique sets, and there is only minimal overlap in ocular miRNA profiling of AMD. Mouse models of AMD, including oxygen-induced retinopathy and laser induced choroidal neovascularization, showed similarities to some extent with miRNA patterns in AMD. For example, miR-146a is an extensively researched miRNA thought to modulate inflammation, and was found to be upregulated in AMD mice and cellular systems, but also in human AMD retinae and vitreous humor. Similarly, mir-17, miR-125b and miR-155 were dysregulated in multiple AMD mouse models as well as in human AMD plasma or retinae. These miRNAs are thought to regulate angiogenesis, apoptosis, phagocytosis, and inflammation. A promising avenue of research is the modulation of such miRNAs, as the phenotype of AMD mice could be ameliorated with antagomirs or miRNA-mimic treatment. However, before meaningful strides can be made to develop miRNAs as a diagnostic or therapeutic tool, reproducible miRNA profiles need to be established for the various clinical outcomes of AMD. PMID- 27658789 TI - Genomic Profiling of Biliary Tract Cancers and Implications for Clinical Practice. AB - OPINION STATEMENT: Biliary tract cancers are relatively uncommon, have an aggressive disease course and a dismal clinical outcome. Until recently, there have been very few clinical advances in the management of these patients and gemcitabine-based chemotherapy has been the only widely accepted systemic therapy. The advent of next generation sequencing technologies can potentially change the treatment paradigm of this disease. Targeted therapy directed against actionable mutations and identification of molecular subsets with distinct prognostic significance is now feasible in clinical practice. Mutation profiling has highlighted the genomic differences between the intra, extrahepatic cholangiocarcinoma, and gallbladder cancer. The mutational spectrum of intrahepatic cholangiocarcinoma differs according to geographic location and ethnicity. There is a higher incidence of chromatin modulating gene mutations in Western patients as compared with Asian patients with liver fluke-associated cholangiocarcinoma. KRAS and p53 mutations are associated with an aggressive disease prognosis while FGFR mutations may signify a relatively indolent disease course of intrahepatic cholangiocarcinoma. FGFR and IDH mutations have promising agents in clinical trials at this time. An estimated 15 % of gallbladder cancers have Her2/neu amplification and can be targeted by trastuzumab. On the other hand, an estimated 10-15 % of cholangiocarcinomas have DNA repair mutations and may be candidates for immune therapies with checkpoint inhibitors. The promise of targeted therapies for biliary tract cancers can be fulfilled with well-designed, prospective, and multi-center clinical trials. PMID- 27658790 TI - Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4. AB - CXCR4 dimerization has been widely demonstrated both biologically and structurally. This paper mainly focused on the development of structure-based dimeric ligands that target CXCL12-CXCR4 interaction and signaling. This study presents the design and synthesis of a series of [PEG]n linked dimeric ligands of CXCR4 based on the knowledge of the homodimeric crystal structure of CXCR4 and our well established platform of chemistry and bioassays for CXCR4. These new ligands include [PEG]n linked homodimeric or heterodimeric peptides consisting of either two DV3-derived moieties (where DV3 is an all-d-amino acid analog of N terminal modules of 1-10 (V3) residues of vMIP-II) or hybrids of DV3 moieties and CXCL121-8. Among a total of 24 peptide ligands, four antagonists and three agonists showed good CXCR4 binding affinity, with IC50 values of <50nM and <800nM, respectively. Chemotaxis and calcium mobilization assays with SUP-T1 cells further identified two promising lead modulators of CXCR4: ligand 4, a [PEG3]2 linked homodimeric DV3, was an effective CXCR4 antagonist (IC50=22nM); and ligand 21, a [PEG3]2 linked heterodimeric DV3-CXCL121-8, was an effective CXCR4 agonist (IC50=407nM). These dimeric CXCR4 modulators represent new molecular probes and therapeutics that effectively modulate CXCL12-CXCR4 interaction and function. PMID- 27658791 TI - Synthesis, characterization, and evaluation of (E)-methyl 2-((2-oxonaphthalen 1(2H)-ylidene)methylamino)acetate as a biological agent and an anion sensor. AB - An amino acid based and bidentate Schiff base, (E)-methyl 2-((2-oxonaphthalen 1(2H)-ylidene)methylamino)acetate (ligand), was synthesized from the reaction of glycine-methyl ester hydrochloride with 2-hydroxy-1-naphthaldehyde. Characterization of the ligand was carried out using theoretical quantum mechanical calculations and experimental spectroscopic methods. The molecular structure of the compound was confirmed using X-ray single-crystal data, NMR, FTIR and UV-Visible spectroscopy, which were in good agreement with the structure predicted by the theoretical calculations using density functional theory (DFT). Antimicrobial activity of the ligand was investigated for its minimum inhibitory concentration (MIC) to several bacteria and yeast cultures. UV-Visible spectroscopy studies also shown that the ligand can bind calf thymus DNA (CT-DNA) electrostatic binding. In addition, DNA cleavage study showed that the ligand cleaved DNA without the need for external agents. Energetically most favorable docked structures were obtained from the rigid molecular docking of the compound with DNA. The compound binds at the active site of the DNA proteins by weak non covalent interactions. The colorimetric response of the ligand in DMSO to the addition of equivalent amount of anions (F-, Br-, I-, CN-, SCN-, ClO4-, HSO4-, AcO-, H2PO4-, N3- and OH-) was investigated and the ligand was shown to be sensitive to CN- anion. PMID- 27658792 TI - Arylsulfonamide derivatives of (aryloxy)ethyl pyrrolidines and piperidines as alpha1-adrenergic receptor antagonist with uro-selective activity. AB - A series of arylsulfonamide derivatives of (aryloxy)ethyl pyrrolidines and piperidines was synthesized to develop new alpha1-adrenoceptor antagonists with uroselective profile. Biological evaluation for alpha1- and alpha2-adrenorecepor showed that tested compounds 13-37 displayed high-to-moderate affinity for the alpha1-adrenoceptor (Ki=34-348nM) and moderate selectivity over alpha2-receptor subtype. Compounds with highest affinity and selectivity for alpha1-adrenoceptor were evaluated in vitro for their intrinsic activity toward alpha1A- and alpha1B adrenoceptor subtypes. All compounds behaved as antagonists at both alpha1 adrenoceptor subtypes, displaying 2- to 6-fold functional preference to alpha1A subtype. Among them, N-{1-[2-(2-methoxyphenoxy)ethyl]piperidin-4-yl}isoquinoline 4-sulfonamide (25) and 3-chloro-2-fluoro-N-{[1-(2-(2 isopropoxyphenoxy)ethyl)piperidin-4-yl]methyl}benzene sulfonamide (34) displayed the highest preference to alpha1A-adrenoceptor. Finally, compounds 25 and 34 (2 5mg/kg, iv), in contrast to tamsulosin (1-2mg/kg, iv), did not significantly decrease systolic and diastolic blood pressure in normotensive anesthetized rats to determine their influence on blood pressure. PMID- 27658793 TI - New inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 7 hydroxycoumarin and monoterpenoid moieties. AB - A number of derivatives of 7-hydroxycoumarins containing aromatic or monoterpene substituents at hydroxy-group were synthesized based on a hit compound from a virtual screen. The ability of these compounds to inhibit tyrosyl-DNA phosphodiesterase I (Tdp 1), important target for anti-cancer therapy, was studied for the first time. It was found that the 7-hydroxycoumarin derivatives with monoterpene pinene moiety are effective inhibitors of Tdp 1 with the most active derivative (+)-25c with IC50 value of 0.675MUM. This compound has low cytotoxicity (CC50>100MUM) when tested against human cancer cells which is crucial for presupposed application in combination with clinically established anticancer drugs. The ability of the new compounds to enhance the cytotoxicity of camptothecin, an established topoisomerase 1 poison, was demonstrated. PMID- 27658794 TI - Synthesis of phenylpiperazine derivatives of 1,4-benzodioxan as selective COX-2 inhibitors and anti-inflammatory agents. AB - 1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-substituted-phenylpiperazine moiety was prepared and has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The biological activity of compound 3k as anti inflammatory agent was further investigated both in vitro and in vivo. Notably, compound 3k exhibited the best anti-inflammatory activity among the eleven designed compounds with no toxicity, as determined by the ulcerogenic activity. Computational docking studies also showed that compound 3k has interaction with COX-2 key residues in the active site. Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic. PMID- 27658795 TI - New antibiotics from Nature's chemical inventory. AB - The doom and gloom of antibiotic resistance dominates public perception of this drug class. Many believe the world has entered the post-antibiotic era. Classic and modern approaches to antibacterial drug discovery have delivered a plethora of lead molecules with a great majority being natural products of ancient microbial origin. The failure of antibiotics in the resistance era comes from an inability to develop new leads into clinical candidates, which is a costly and risky endeavor for any therapeutic area, especially when resistance is at play. The world needs new antibiotic molecules to replace the exhausted pipeline and the second 'golden era' is certain to come from Nature's chemical inventory once again. PMID- 27658796 TI - Advances in rationally designed dual inhibitors of HIV-1 reverse transcriptase and integrase. AB - Reverse transcriptase (RT) and integrase (IN) are two indispensable enzymes in human immunodeficiency virus type 1 (HIV-1) replication. RT is responsible for the transformation of the single-stranded RNA viral genome into double-stranded DNA, and IN catalyzes the integration of viral DNA into the host DNA. Although highly active antiretroviral therapy (HAART) combining nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) with nonnucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) could suppress successfully HIV viral load and reduce evidently the mortality of HIV infected people, it involves the difficulty of perfect adherence, and other drawbacks such as viral rebound, toxicities and multi-drug resistances. Recently, rational drug design has become a dominant technique for the development of multi-target drugs. And the rationally designed dual inhibitors of HIV-1 RT and IN have become a hot topic of anti-HIV research. In this review, the advances in rationally designed dual inhibitors of HIV-1 RT and IN were summarized, including structurally diverse inhibitors, their structure-activity relationship (SAR) studies as well as binding mode analysis. PMID- 27658797 TI - Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues. AB - Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists. PMID- 27658798 TI - 8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors. AB - Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A2A adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A1 ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1 f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A1 and A2AARs at similar concentrations representing dual A1/A2A antagonists with high selectivity versus the other AR subtypes. Among the best dual A1/A2AAR antagonists were 8-(3-(4-chlorophenyl)propyl)-1,3-dimethyl 6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (41, Ki human A1: 65.5nM, A2A: 230nM; Ki rat A1: 352nM, A2A: 316nM) and 1,3-dimethyl-8-((2 (thiophen-2-yl)thiazol-4-yl)methyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine 2,4(1H,3H)-dione (57, Ki human A1: 642nM, A2A: 203nM; Ki rat A1: 166nM, A2A: 121nM). Compound 57 was found to be well water-soluble (0.7mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple-target inhibition: (R)-1,3-dimethyl-8-(2,1,3,4-tetrahydronaphthalen-1-yl)-6,7,8,9 tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (49) was about equipotent at A1 and A2AARs and at MAO-B (Ki human A1: 393nM, human A2A: 595nM, IC50 human MAO-B: 210nM) thus allowing future in vivo explorations of the intended multi-target approach. PMID- 27658799 TI - Factors affecting whether or not cancer patients consider using acupuncture. AB - OBJECTIVE: To explore the factors associated with utilisation of an acupuncture service in a tertiary oncology setting in an Australian public hospital. METHOD: Cancer patients attending oncology clinics at a university teaching hospital were invited to participate in the evaluation of acupuncture services from June 2014 to May 2015. Patients had a prior diagnosis of cancer (albeit at different stages) and were planning to receive, or were already receiving, systemic and/or radiation cancer treatment. RESULTS: The majority (81%) of participants indicated that they would consider the use of acupuncture during their cancer treatment. The most common reasons given for not considering acupuncture included adequate control of symptoms already with medical treatment, inconvenient clinic timing, and needle phobia. The main reasons given for considering acupuncture use included its perceived capability of reducing fatigue, boosting energy levels, improving immune function, and reducing pain and anxiety. Patients considering acupuncture use also demonstrated significantly higher levels of stress (p<0.001), anxiety and depression (p<0.001), fatigue (p<0.001), and lower global quality of life (p<0.01) compared to those who were not considering acupuncture. CONCLUSIONS: The findings show that demand for acupuncture by cancer patients is high. A substantial proportion of cancer patients intend to use acupuncture to manage cancer and/or cancer treatment-related symptoms. Discussion with patients about acupuncture and other complementary therapies during the consultation may improve cancer care. PMID- 27658800 TI - Protic N-Heterocyclic Carbene Versus Pyrazole: Rigorous Comparison of Proton- and Electron-Donating Abilities in a Pincer-Type Framework. AB - Evaluation of the acidity of proton-responsive ligands such as protic N heterocyclic carbenes (NHCs) bearing an NH-wingtip provides a key to understanding the metal-ligand cooperation in enzymatic and artificial catalysis. Here, we design a CNN pincer-type ruthenium complex 2 bearing protic NHC and isoelectronic pyrazole units in a symmetrical skeleton, to compare their acidities and electron-donating abilities. The synthesis is achieved by direct C H metalation of 2-(imidazol-1-yl)-6-(pyrazol-3-yl)pyridine with [RuCl2 (PPh3 )3 ]. 15 N-Labeling experiments confirm that deprotonation of 2 occurs first at the pyrazole side, indicating clearly that the protic pyrazole is more acidic than the NHC group. The electrochemical measurements as well as derivatization to carbonyl complexes demonstrate that the protic NHC is more electron-donating than pyrazole in both protonated and deprotonated forms. PMID- 27658801 TI - Development of mouse models of malignant phyllodes tumors by transplantation of syngeneic mammary gland cells expressing mutant H-Ras. AB - Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast with epithelial and stromal components, and surgical resection is the standard and only available treatment for malignant PTs. To provide a better understanding of these tumors, we developed mouse models that recapitulate the pathological and clinical properties of human malignant PTs. Mouse undifferentiated mammary gland cells were infected with a retrovirus encoding the human oncoprotein H-RasG12V , and the infected cells were transplanted orthotopically into the mammary fat pads of syngeneic mice. The transplanted cells showed a high tumorigenic activity, with the resulting tumors manifesting pathological characteristics including stromal overgrowth similar to those of human malignant PTs. The tumors also showed high rates of both local recurrence and lung metastasis. Our models may prove useful for studies of the pathophysiology of malignant PTs as well as facilitate the development of new treatments. PMID- 27658803 TI - The boss is always right: Preschoolers endorse the testimony of a dominant over that of a subordinate. AB - Recent research has shown that young children rely on social cues to evaluate testimony. For instance, they prefer to endorse testimony provided by a consensual group than by a single dissenter. Given that dominance is pervasive in children's social environment, it can be hypothesized that children also use dominance relations in their selection of testimony. To test this hypothesis, a dominance asymmetry was induced between two characters either by having one repeatedly win in physical contests (physical power; Experiment 1) or by having one repeatedly impose her goals on the other (decisional power; Experiment 2). In two subsequent testimony tasks, 3- to 5-year-old children significantly tended to endorse the testimony of the dominant over that of the subordinate. These results suggest that preschoolers take dominance into account when evaluating testimony. In conclusion, we discuss two potential explanations for these findings. PMID- 27658802 TI - Overview of the SAMPL5 host-guest challenge: Are we doing better? AB - The ability to computationally predict protein-small molecule binding affinities with high accuracy would accelerate drug discovery and reduce its cost by eliminating rounds of trial-and-error synthesis and experimental evaluation of candidate ligands. As academic and industrial groups work toward this capability, there is an ongoing need for datasets that can be used to rigorously test new computational methods. Although protein-ligand data are clearly important for this purpose, their size and complexity make it difficult to obtain well converged results and to troubleshoot computational methods. Host-guest systems offer a valuable alternative class of test cases, as they exemplify noncovalent molecular recognition but are far smaller and simpler. As a consequence, host guest systems have been part of the prior two rounds of SAMPL prediction exercises, and they also figure in the present SAMPL5 round. In addition to being blinded, and thus avoiding biases that may arise in retrospective studies, the SAMPL challenges have the merit of focusing multiple researchers on a common set of molecular systems, so that methods may be compared and ideas exchanged. The present paper provides an overview of the host-guest component of SAMPL5, which centers on three different hosts, two octa-acids and a glycoluril-based molecular clip, and two different sets of guest molecules, in aqueous solution. A range of methods were applied, including electronic structure calculations with implicit solvent models; methods that combine empirical force fields with implicit solvent models; and explicit solvent free energy simulations. The most reliable methods tend to fall in the latter class, consistent with results in prior SAMPL rounds, but the level of accuracy is still below that sought for reliable computer-aided drug design. Advances in force field accuracy, modeling of protonation equilibria, electronic structure methods, and solvent models, hold promise for future improvements. PMID- 27658804 TI - Comparison of Functional Recovery is Crucial for Implementing ERAS: Reply. PMID- 27658805 TI - The Quality and Utility of Surgical and Anesthetic Data at a Ugandan Regional Referral Hospital. AB - BACKGROUND: There are little primary data available on the delivery or quality of surgical treatment in rural sub-Saharan African hospitals. To initiate a quality improvement system, we characterized the existing data capture at a Ugandan Regional Referral Hospital. METHODS: We examined the surgical ward admission (January 2008-December/2011) and operating theater logbooks (January 2010-July 2011) at Mbarara Regional Referral Hospital. RESULTS: There were 6346 admissions recorded over three years. The mean patient age was 31.4 +/- 22.3 years; 29.8 % (n = 1888) of admissions were children. Leading causes of admission were general surgical problems (n = 3050, 48.1 %), trauma (n = 2041, 32.2 %), oncology (n = 718, 11.3 %) and congenital condition (n = 193, 3.0 %). Laparotomy (n = 468, 35.3 %), incision and drainage (n = 188, 14.2 %) and hernia repair (n = 90, 6.8 %) were the most common surgical procedures. Of 1325 operative patients, 994 (75 %) had an ASA I-II score. Of patients undergoing 810 procedures booked as non elective, 583 (72 %) had an ASA "E" rating. Records of 41.3 % (n-403/975) of patients age 5 years or older undergoing non-obstetric operations were missing from the ward logbook. Missing patients were younger (25 [13,40] versus 30 [18,46] years, p = 0.002) and had higher ASA scores (ASA III-V 29.0 % versus 18.9 %, p < 0.001) than patients recorded in the logbbook; there was no diffence in gender (male 62.8 % versus 67.0 %, p = 0.20). CONCLUSIONS: The hospital records system measures surgical care, but improved data capture is needed to determine outcomes with sufficient accuracy to guide and record expansion of surgical capacity. PMID- 27658807 TI - Prediction of prostate cancer recurrence using quantitative phase imaging: Validation on a general population. AB - Prediction of biochemical recurrence risk of prostate cancer following radical prostatectomy is critical for determining whether the patient would benefit from adjuvant treatments. Various nomograms exist today for identifying individuals at higher risk for recurrence; however, an optimistic under-estimation of recurrence risk is a common problem associated with these methods. We previously showed that anisotropy of light scattering measured using quantitative phase imaging, in the stromal layer adjacent to cancerous glands, is predictive of recurrence. That nested-case controlled study consisted of specimens specifically chosen such that the current prognostic methods fail. Here we report on validating the utility of optical anisotropy for prediction of prostate cancer recurrence in a general population of 192 patients, with 17% probability of recurrence. Our results show that our method can identify recurrent cases with 73% sensitivity and 72% specificity, which is comparable to that of CAPRA-S, a current state of the art method, in the same population. However, our results show that optical anisotropy outperforms CAPRA-S for patients with Gleason grades 7-10. In essence, we demonstrate that anisotropy is a better biomarker for identifying high-risk cases, while Gleason grade is better suited for selecting non-recurrence. Therefore, we propose that anisotropy and current techniques be used together to maximize prediction accuracy. PMID- 27658806 TI - Cutaneous manifestations of graft-versus-host disease: role of the dermatologist. AB - Graft-versus-host disease (GVHD) is the major complication of hematopoietic stem cell transplantation and is associated with high mortality in severe cases. The skin is one of the major organs affected in both acute and chronic GVHD. This review aims to elucidate the basic characteristics of GVHD, and the role and contribution of dermatologists in the care of patients with this condition. PMID- 27658808 TI - Comparative Risk Analysis of Two Culicoides-Borne Diseases in Horses: Equine Encephalosis More Likely to Enter France than African Horse Sickness. AB - African horse sickness (AHS) and equine encephalosis (EE) are Culicoides-borne viral diseases that could have the potential to spread across Europe if introduced, thus being potential threats for the European equine industry. Both share similar epidemiology, transmission patterns and geographical distribution. Using stochastic spatiotemporal models of virus entry, we assessed and compared the probabilities of both viruses entering France via two pathways: importation of live-infected animals or importation of infected vectors. Analyses were performed for three consecutive years (2010-2012). Seasonal and regional differences in virus entry probabilities were the same for both diseases. However, the probability of EE entry was much higher than the probability of AHS entry. Interestingly, the most likely entry route differed between AHS and EE: AHS has a higher probability to enter through an infected vector and EE has a higher probability to enter through an infectious host. Consequently, different effective protective measures were identified by 'what-if' scenarios for the two diseases. The implementation of vector protection on all animals (equine and bovine) coming from low-risk regions before their importation was the most effective in reducing the probability of AHS entry. On the other hand, the most significant reduction in the probability of EE entry was obtained by the implementation of quarantine before import for horses coming from both EU and non EU countries. The developed models can be useful to implement risk-based surveillance. PMID- 27658809 TI - Population Fluctuation and Altitudinal Distribution of Tetraleurodes perseae (Nakahara) (Hemiptera: Aleyrodidae) in Avocado (Lauraceae) in Morelos, Mexico. AB - Although whiteflies Tetraleurodes perseae (Nakahara) (Hemiptera: Aleyrodidae) are considered a secondary pest of avocado crops, their presence and the damages that they cause can decrease crop vigor and affect production. The objective of the present work was to determine the population fluctuation and altitudinal distribution of the T. perseae Nakahara whitefly in avocado trees, as well as to determine the number of possible generations in one year. The study was done in three orchards in Morelos state, located at different altitudes, from February 2014 to April 2015. Samplings were done every 21 days from 10 randomly chosen trees in each orchard. The samples were taken randomly from the middle stratus (1.6 m in height) of each tree; in buds or young leaves for the number of adults and leaves only for nymphs. Additionally, two yellow traps (7 * 14 cm) with glue were placed in each tree for adult samplings. Data were collected regarding vegetative budding, rainfall, relative humidity, and temperature. T. perseae was present in all three sampled orchards, with a greater presence in the lowest orchard, during the whole study period. In the orchard with the lowest altitudinal gradient (1,736 masl), 11 whitefly generations developed; 10 generations developed in the medium gradient orchard (1,934 masl); and 8 generations developed in the highest orchard (2,230 masl). The adults showed a positive relationship with regard to vegetative buds, while the nymphs had a negative relationship with regard to relative humidity. The rest of the parameters showed diverse effects on the species depending on the altitude of the orchard. PMID- 27658810 TI - Soluble VEGFR1 reverses BMP2 inhibition of intramembranous ossification during healing of cortical bone defects. AB - BMP2 is widely used for promotion of bone repair and regeneration. However, bone formation induced by BMP2 is quite variable. Bone forming progenitor cells in different locations appear to respond to BMP2 in different ways, and repair outcomes can vary as a consequence of modulating effects by other factors. In this study, we have examined the effects of VEGF on BMP2-induced repair of a cortical bone defect, a 1 mm diameter drill hole, in the proximal tibia of mice. Treatment of the defect with either a bolus of PBS or soluble VEGFR1 (sVEGFR1), a decoy receptor for VEGF, had the same effects on bone formation via intramembranous ossification in the defect and cartilage formation and injured periosteum, during the healing process. In contrast, treatment with BMP2 inhibited intramembranous bone formation in the defect while it promoted cartilage and endochondral bone formation in the injured periosteum compared with mice treated with PBS or sVEGFR1. The inhibitory effect of BMP2 on bone formation was unlikely due to increased osteoclast activity and decreased invasion of blood vessels in the defect. Most importantly, co-delivery of BMP2 and sVEGFR1 reversed the inhibition of intramembranous bone formation by BMP2. Furthermore, the decreased accumulation of collagen and production of bone matrix proteins in the defect of groups with BMP2 treatment could also be prevented by co-delivery of BMP2 and sVEGFR1. Our data indicate that introducing a VEGF-binding protein, such as sVEGFR1, to reduce levels of extracellular VEGF, may enhance the effects of BMP2 on intramembranous bone formation. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1461-1469, 2017. PMID- 27658811 TI - Self-harm in adolescence: protective health assets in the family, school and community. AB - OBJECTIVES: The aim of this paper was to examine if the multiple environments of the adolescent including family, peers, school and neighbourhood might function as protective health assets against self-harming behaviour during adolescence. METHODS: The present study utilised data collected from 1608 respondents aged 15 years as part of the England WHO Health Behaviour in School-aged Children (HBSC) Study. Multilevel modelling was undertaken using the package MLwiN (version 2.33) to investigate the potential domains and dimensions of family life, school culture and environment, and neighbourhood factors that may operate as protective health assets. RESULTS: The results indicated that while peer support did not appear to operate as a protective health asset in the context of self-harm, key dimensions of adolescent/parent interaction and adolescent experience of the school culture and their neighbourhood were associated with reduced likelihood of self-harming behaviours during adolescence. CONCLUSIONS: The Findings highlight the significance of belonging and connectedness as important constituent elements of protective health assets for young people. Interventions that address the multiple environments of the young person, may offer an effective means to reduce the levels of self-harm. PMID- 27658812 TI - Sociocultural determinants of anticipated acceptance of pandemic influenza vaccine in Pune, India: a community survey using mixed-methods. AB - OBJECTIVES: To investigate community priority and determinants of pandemic influenza vaccine acceptance in Pune, India. Community willingness to accept vaccines is often neglected in pandemic preparedness. Despite an acknowledged need, few such studies have been done in lower income countries. METHODS: A cross sectional, mixed-methods study used semi-structured explanatory model interviews to assess anticipated acceptance of nasal and injectable vaccines at different prices among 436 urban and rural residents. Logistic regression models identified sociocultural determinants of vaccine acceptance. RESULTS: Over 93 % anticipated acceptance at no-cost; 87.8 % for INR 150 nasal vaccine; 74.1 % for INR 500 and 61.7 % for INR 1000 injectable vaccines. Some respondents preferred low-cost over free vaccines. Illness-related concerns about social isolation, contaminants identified as perceived causes, private-hospital or traditional-healer help seeking, and income were positively associated with anticipated acceptance. Humoral imbalances as perceived cause, home remedies for help-seeking and age were negatively associated. CONCLUSIONS: High acceptability of pandemic influenza vaccines indicates good prospects for mass vaccination. It appeared that confidence was higher in the vaccines than in the health systems delivering them. Vaccination programmes should consider sociocultural determinants influencing vaccine acceptance. PMID- 27658814 TI - Infliximab biosimilars are safe, effective, and cheap, UK audit shows. PMID- 27658813 TI - (Non-)utilization of pre-hospital emergency care by migrants and non-migrants in Germany. AB - OBJECTIVES: This study was designed to explore the utilization and non utilization of pre-hospital emergency care by migrants and non-migrants, and the factors that influence this behaviour. METHODS: A cross-sectional representative German survey was conducted in a sample of 2.175 people, 295 of whom had a migration background. An additional sample of 50 people with Turkish migration background was conducted, partially in the Turkish language. Apart from socio demographics, the utilization of emergency services and the reasons for non utilization were assessed. RESULTS: Migrants had a higher utilization rate of pre hospital emergency care (RR = 1.492) than non-migrants. Furthermore, migrants who were not born in Germany had a lower utilization rate (RR = 0.793) than migrants who were born in Germany. Regarding non-utilization, the most frequently stated reasons belonged to the categories initial misjudgment of the emergency situation and acting on one's own behalf, with the latter stated more frequently by migrants than by non-migrants. CONCLUSIONS: To prevent over-, under-, and lack of supply, it is necessary to transfer knowledge about the functioning of the medical emergency services, including first aid knowledge. PMID- 27658816 TI - Characterizing the drivers of seedling leaf gas exchange responses to warming and altered precipitation: indirect and direct effects. AB - Anthropogenic forces are projected to lead to warmer temperatures and altered precipitation patterns globally. The impact of these climatic changes on the uptake of carbon by the land surface will, in part, determine the rate and magnitude of these changes. However, there is a great deal of uncertainty in how terrestrial ecosystems will respond to climate in the future. Here, we used a fully factorial warming (four levels) by precipitation (three levels) manipulation experiment in an old-field ecosystem in the northeastern USA to examine the impact of climatic changes on leaf carbon exchange in five species of deciduous tree seedlings. We found that photosynthesis generally increased in response to increasing precipitation and decreased in response to warming. Respiration was less sensitive to the treatments. The net result was greater leaf carbon uptake in wetter and cooler conditions across all species. Structural equation modelling revealed the primary pathway through which climate impacted leaf carbon exchange. Net photosynthesis increased with increasing stomatal conductance and photosynthetic enzyme capacity (Vcmax), and decreased with increasing respiration of leaves. Soil moisture and leaf temperature at the time of measurement most heavily influenced these primary drivers of net photosynthesis. Leaf respiration increased with increasing soil moisture, leaf temperature, and photosynthetic supply of substrates. Counter to the soil moisture response, respiration decreased with increasing precipitation amount, indicating that the response to short- (i.e. soil moisture) versus long-term (i.e. precipitation amount) water stress differed, possibly as a result of changes in the relative amounts of growth and maintenance demand for respiration over time. These data (>500 paired measurements of light and dark leaf gas exchange), now publicly available, detail the pathways by which climate can impact leaf gas exchange and could be useful for testing assumptions in land surface models. PMID- 27658815 TI - Surgical outcomes after instrumented lumbar surgery in patients of eighty years of age and older. AB - BACKGROUND: In Taiwan, the life expectancy of an 80-year-old man is 88.4 years and the life expectancy of an 80-year-old woman is 89.8 years. Some of these people will develop symptomatic degenerative lumbar diseases that interfere with an active lifestyle. These older surgical candidates usually ask the surgeon whether it would be safe to undergo surgery. However, there is no literature assessing the outcomes of laminectomy, fusion and posterior fixation for degenerative lumbar diseases in patients older than 80 years. The purpose of this study was to report the surgical outcomes of patients 80 years of age and older who underwent spinal decompression and instrumented lumbar arthrodesis for degeneration lumbar diseases. METHODS: We retrospectively reviewed patients with degenerative lumbar diseases and spinal stenosis who underwent surgery between January 2010 and December 2012. Inclusion criteria were age greater than or equal to 80 years, decompression with instrumented lumbar arthrodesis, and at least 2 years of follow-up. Totally 89 patients were studies. Clinical outcomes were evaluated according to the Oswestry Disability Index (ODI) and visual analogue scale (VAS) of leg and back pain. Plain radiographs (lateral, anteroposterior, and flexion-extension) were used to assess the status of fusion and implant related complications. Every complication during admission and any implant related or failed-back syndrome requiring a second surgery was documented. T test and Fisher's exact test were used for statistical analysis. RESULTS: Five patients were lost to follow-up, and another 12 died during the follow-up period. One patient died due to cerebral stroke just 2 days after surgery, and the other 11 patients passed away 3 months to 4 years postoperatively. In all, 72 patients had an adequate follow-up: 44 were female and 28 were male. The average age at surgery was 82.5 +/- 2.6 years (80 to 93); 63 patients underwent their first lumbar surgery, and nine patients received a second surgery. Patients underwent arthrodesis surgeries were from a single-level to a 7-level. Four patients developed complications (5.6 %, 4/72). At the final follow-up, the average ODI score was lower than the preoperative score (30.0 vs. 61.8) (p < 0.001). The average VAS score also showed improvement (leg: p < 0.001; back: p < 0.001). Forty-three patients were classified as "satisfied", and 29 were "dissatisfied". Longer operation time (p = 0.014) and development of complications (p = 0.049) were related to poor clinical results. Radiographic follow-up showed that 53 patients had solid union, ten had a probable union, and nine had pseudarthrosis. More surgical segments led to a greater chance of pseudarthrosis (2.0 +/- 0.9 vs 3.0 +/- 1.8, p = 0.003). CONCLUSION: Longer instrumented segments and development of complications contributed to worse clinical and radiographic outcomes. With proper patient selection, posterior decompression with instrumented fusion can be safe and effective for patients 80 years of age and older with degenerative lumbar conditions. PMID- 27658818 TI - High male fertility in males of a subdioecious shrub in hand-pollinated crosses. AB - Female reproductive success in females versus hermaphrodites has been well documented. However, documenting a potential advantage in male fertility of male versus hermaphrodite individuals in subdioecious species is also essential for understanding the evolutionary pathway toward dioecy from hermaphroditism via gynodioecy. Siring success in terms of fruit set, fruit mass, number of seeds and mean seed mass was compared by hand-pollinated crosses in the subdioecious shrub Eurya japonica The pollen was from male and hermaphrodite individuals, and the pollen recipients were females and hermaphrodites. Seed quality was also evaluated in terms of seed germination rate, seed germination day and seedling survival. Overall, pollen from males sired more fruits of larger size and more seeds than did pollen from hermaphrodites. The male advantage was observed when pollen recipients were females, whereas no effect was found in hermaphrodite recipients. Pollen from males also produced better quality seeds with higher germination rate and sooner germination day. Although these results could also be explained by a higher pollen load for crosses with male pollen donors, we took care to saturate the stigma regardless of the pollen donor. Therefore, these results suggest that male individuals of E. japonica have advantages in male fertility in terms of both quantity and quality. Our previous studies indicated that females exhibit higher female reproductive success compared with hermaphrodites. Thus, both the female and male functions of hermaphrodites are outperformed by females and males, respectively, raising the possibility that the subdioecious E. japonica at this study site is entering the transitional phase to dioecy along the gynodioecy-dioecy pathway. PMID- 27658819 TI - A unique patterned diamond stamp for a periodically hierarchical nanoarray structure. AB - A diamond stamp with a hierarchical pattern was designed for the direct preparation of a periodic nanoarray structure, which was prepared by the reactive ion etching technique with a hierarchical ultrathin alumina membrane (HUTAM) as a mask. The optimal etching conditions for fabricating the diamond stamp were discussed in order to realize a vertical nanopore structure, avoiding structural damage from lateral etching. By using this diamond stamp, a polymer film with the desired hierarchical nanorod array structure can be obtained easily via the simple stamping process, which greatly simplifies the processing procedure. More importantly, the stamp is reusable because of its super-hardness, which ensures the reproducibility of the nanorod array pattern. Another merit is that the smooth surface of the etched diamond can avoid the use of a release agent. Our results prove that this hard stamp can be used for quick preparation of an elaborate periodic nanoarray structure. This study is significant in that it solves the problems of high cost and easy damage of stamps in nanoimprint lithography, and it might inspire more sophisticated applications of such an ordered structure in nanoplasmonics, biochemical sensing and nanophotonic devices. PMID- 27658817 TI - Host specificity in parasitic plants-perspectives from mistletoes. AB - Host specificity has been investigated for centuries in mistletoes, viruses, insects, parasitoids, lice and flukes, yet it is poorly understood. Reviewing the numerous studies on mistletoe host specificity may contribute to our understanding of these plants and put into context the dynamics at work in root parasitic plants and animal parasites. The mechanisms that determine host specificity in mistletoes are not as well documented and understood as those in other groups of parasites. To rectify this, we synthesized the available literature and analyzed data compiled from herbaria, published monographs and our own field studies in South Africa. As for other groups of parasites, multiple factors influence mistletoe host specificity. Initially, pollination affects gene flow. Subsequently, seed dispersal vectors (birds and marsupials), host abundance and compatibility (genetic, morphological, physiological and chemical), history and environmental conditions affect the interaction of mistletoes and their hosts and determine host specificity. Mistletoe-host network analyses and a geographic mosaic approach combined with long-term monitoring of reciprocal transplant experiments, genetic analyses of confined mistletoe populations and comparative phylogenetic studies could provide further insights to our understanding of host specificity. Some of these approaches have been used to study animal-plant interactions and could be adopted to test and evaluate host specificity in mistletoes at local and larger geographic scales. PMID- 27658821 TI - Single particle electron cryomicroscopy: trends, issues and future perspective. AB - There has been enormous progress during the last few years in the determination of three-dimensional biological structures by single particle electron cryomicroscopy (cryoEM), allowing maps to be obtained with higher resolution and from fewer images than required previously. This is due principally to the introduction of a new type of direct electron detector that has 2- to 3-fold higher detective quantum efficiency than available previously, and to the improvement of the computational algorithms for image processing. In spite of the great strides that have been made, quantitative analysis shows that there are still significant gains to be made provided that the problems associated with image degradation can be solved, possibly by minimising beam-induced specimen movement and charge build up during imaging. If this can be achieved, it should be possible to obtain near atomic resolution structures of smaller single particles, using fewer images and resolving more conformational states than at present, thus realising the full potential of the method. The recent popularity of cryoEM for molecular structure determination also highlights the need for lower cost microscopes, so we encourage development of an inexpensive, 100 keV electron cryomicroscope with a high-brightness field emission gun to make the method accessible to individual groups or institutions that cannot afford the investment and running costs of a state-of-the-art 300 keV installation. A key requisite for successful high-resolution structure determination by cryoEM includes interpretation of images and optimising the biochemistry and grid preparation to obtain nicely distributed macromolecules of interest. We thus include in this review a gallery of cryoEM micrographs that shows illustrative examples of single particle images of large and small macromolecular complexes. PMID- 27658820 TI - Feasibility and validity of a statistical adjustment to reduce self-report bias of height and weight in wave 1 of the Add Health study. AB - BACKGROUND: Bias in adolescent self-reported height and weight is well documented. Given the importance and widespread use of the National Longitudinal Study of Adolescent to Adult Health (Add Health) data for obesity research, we developed and tested the feasibility and validity of an empirically derived statistical correction for self-report bias in wave 1 (W1) of Add Health, a large panel study in the United States. METHODS: Participants in grades 7-12 with complete height and weight data at W1 were included (n = 20,175). We used measured and self-reported (SR) height and weight and relevant biopsychosocial factors from wave 2 (W2) of Add Health (n = 14,190) to identify sources of bias and derive the most efficient sex-specific estimates of corrected height and weight. Measured, SR, and corrected W2 BMI values were calculated and compared, including sensitivity and specificity. Final correction equations were applied to W1. RESULTS: After correction, weight status misclassification rates among those who underestimated their weight status were reduced from 6.6 to 5.7 % for males and from 8.0 to 5.6 % for females compared to self-report; and the correlation between SR and measured BMI in W2 increased slightly from 0.92 to 0.93. Among females, correction procedures resulted in a 3.4 % increase in sensitivity to detect overweight/obesity (BMI >= 25) and 5.9 % increase in sensitivity for obesity (BMI >= 30). CONCLUSIONS: Findings suggest that application of the proposed statistical corrections can reduce bias of self-report height and weight in W1 of the Add Health data and may be useful in some analyses. In particular, the corrected BMI values improve sensitivity --the ability to detect a true positive-for overweight/obesity among females, which addresses a major concern about self-report bias in obesity research. However, the correction does not improve sensitivity to identify underweight or healthy weight adolescents and so should be applied selectively based on research questions. PMID- 27658822 TI - Fibrous shape underlies the mutagenic and carcinogenic potential of nanosilver while surface chemistry affects the biosafety of iron oxide nanoparticles. AB - Nowadays engineered nanomaterials (ENMs) are increasingly used in a wide range of commercial products and biomedical applications. Despite this, the knowledge of human potential health risk as well as comprehensive biological and toxicological information is still limited. We have investigated the capacity of two frequently used metallic ENMs, nanosilver and magnetite nanoparticles (MNPs), to induce thymidine kinase (Tk +/-) mutations in L5178Y mouse lymphoma cells and transformed foci in Bhas 42 cells. Two types of nanosilver, spherical nanoparticles (AgNM300) and fibrous (AgNM302) nanorods/wires, and MNPs differing in surface modifications [MNPs coated with sodium oleate (SO-MNPs), MNPs coated with SO + polyethylene glycol (SO-PEG-MNPs) and MNPs coated with SO + PEG + poly(lactide-co-glycolic acid) SO-PEG-PLGA-MNPs] were included in this study. Spherical AgNM300 showed neither mutagenic nor carcinogenic potential. In contrast, silver nanorods/wires (AgNM302) increased significantly the number of both gene mutations and transformed foci compared with the control (untreated) cells. Under the same treatment conditions, neither SO-MNPs nor SO-PEG-PLGA-MNPs increased the mutant frequency compared with control cells though an equivocal mutagenic effect was estimated for SO-PEG-MNPs. Although SO-MNPs and SO-PEG-MNPs did not show any carcinogenic potential, SO-PEG-PLGA-MNPs increased concentration dependently the number of transformed foci in Bhas 42 cells compared with the control cells. Our results revealed that fibrous shape underlies the mutagenic and carcinogenic potential of nanosilver while surface chemistry affects the biosafety of MNPs. Considering that both nanosilver and MNPs are prospective ENMs for biomedical applications, further toxicological evaluations are warranted to assess comprehensively the biosafety of these nanomaterials. PMID- 27658824 TI - Hemophagocytic lymphohistiocytosis responding to withdrawal of gluten: a case report. AB - BACKGROUND: This is the first documented case of a patient with hemophagocytic lymphohistiocytosis in association with coeliac disease. There was complete clinical and biochemical remission of hemophagocytic lymphohistiocytosis following the introduction of a gluten-free diet. CASE PRESENTATION: A 7-year-old white girl presented with fevers and maculopapular rash with a recent history of tonsillitis. Blood tests revealed thrombocytopenia (64*109/L), anemia (80 g/L), hypofibrinogenemia (1 g/L), and hyperferritinemia (71,378 MUg/L). A bone marrow revealed evidence of hemophagocytosis, but the results of tests for the genetic or familial-associated hemophagocytic lymphohistiocytosis syndromes were negative. The results of screening tests for known secondary causes were negative. She was diagnosed as having hemophagocytic lymphohistiocytosis and following treatment with the hemophagocytic lymphohistiocytosis-2004 protocol these symptoms, in addition to the biochemical and hematological markers, completely resolved. She presented again 10 months later with fever, rash, and biochemical abnormalities suggestive of hemophagocytic lymphohistiocytosis. Her tissue transglutaminase was markedly raised and the results of blood tests revealed a genetic susceptibly to coeliac disease in the form of HLA-DQ2 positivity. She commenced a gluten-free diet and there was complete symptomatic and biochemical response without any further chemotherapy. She had further episodic rashes, each associated with the accidental intake of gluten. CONCLUSIONS: This is to the best of our knowledge the first documented case of hemophagocytic lymphohistiocytosis in association with coeliac disease. No other secondary cause found; she initially responded to chemoimmunotherapy specific for hemophagocytic lymphohistiocytosis but relapsed within a few months of cessation of treatment and then achieved complete remission on gluten withdrawal alone. PMID- 27658823 TI - Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice. AB - The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 ug/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dose-dependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung tissue at all assessed time points. There was no statistically significant difference between NRCWE-001 and NRCWE-002. Exposure to both TiO2 NPs induced increased levels of DNA strand breaks in lung tissue at all doses 1 and 28 days post-exposure and NRCWE-002 at the low and middle dose 3 days post-exposure. The DNA strand break levels were statistically significantly different for NRCWE-001 and -002 for liver and for BAL cells, but no consistent pattern was observed. In conclusion, functionalisation of reactive negatively charged rutile TiO2 to positively charged did not consistently influence pulmonary toxicity of the studied TiO2 NPs. PMID- 27658825 TI - A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer. AB - BACKGROUND: Sequential biopsy of breast cancer is used to assess biomarker effects and drug efficacy. The preoperative "window of opportunity" setting is advantageous to test biomarker changes in response to therapeutic agents in previously untreated primary cancers. This study tested the consistency over time of paired, sequential biomarker measurements on primary, operable breast cancer in the absence of drug therapy. METHODS: Immunohistochemistry was performed for ER, PR and Ki67 on paired preoperative/operative tumor samples taken from untreated patients within 2 weeks of each other. Microarray analysis on mRNA extracted from formalin fixed paraffin embedded cores was performed using Affymetrix based arrays on paired core biopsies analysed using Ingenuity Pathway Analysis (IPA) and Gene Set Analysis (GSA). RESULTS: In 41 core/resection pairs, the recognised trend to lower ER, PR and Ki67 score on resected material was confirmed. Concordance for ER, PR and Ki67 without changing biomarker status (e.g. ER+ to ER-) was 90, 74 and 80 % respectively. However, in 23 paired core samples (diagnostic core v on table core), Ki67 using a cut off of 13.25 % was concordant in 22/23 (96 %) and differences in ER and PR immunohistochemistry by Allred or Quickscore between the pairs did not impact hormone receptor status. IPA and GSA demonstrated substantial gene expression changes between paired cores at the mRNA level, including reduced expression of ER pathway analysis on the second core, despite the absence of drug intervention. CONCLUSIONS: Sequential core biopsies of primary breast cancer (but not core versus resection) was consistent and is appropriate to assess the effects of drug therapy in vivo on ER, PR and Ki67 using immunohistochemistry. Conversely, studies utilising mRNA expression may require non-treatment controls to distinguish therapeutic from biopsy differences. PMID- 27658826 TI - Correlation between serum levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and atherogenic lipoproteins in patients with coronary artery disease. AB - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein (LDL) cholesterol levels. Recently, PCSK9 has additionally been related to metabolic risk factors such as the levels of triglycerides, apolipoprotein B (apoB), insulin, and glucose, as well as body mass index. The purpose of this study was to investigate correlations between serum levels of PCSK9 and apoB-containing atherogenic lipoproteins in patients with coronary artery disease (CAD). METHODS: Serum levels of PCSK9 and lipoprotein(a) [Lp(a)]; small, dense LDL; and oxidized LDL were measured in 101 patients with CAD who were not receiving lipid-lowering therapy. RESULTS: Serum hetero-dimer PCSK9 levels were positively correlated with serum levels of Lp(a) (r = 0.195, p = 0.05); small, dense LDL (r = 0.336, p = 0.0006); and oxidized LDL (r = 0.268, p = 0.008). Multivariate regression analyses showed that serum hetero dimer PCSK9 was a significant predictor of serum levels of Lp(a) (beta = 0.235, p = 0.01); small, dense LDL (beta = 0.143, p = 0.03); and oxidized LDL (beta = 0.268, p = 0.008). CONCLUSIONS: Serum PCSK9 levels were positively correlated with serum levels of Lp(a); small, dense LDL; and oxidized LDL in patients with CAD. This suggests that the interaction between serum PCSK9 and apoB-containing lipoproteins plays a role in establishing the atherosclerotic status of patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN ID: C000000311 . PMID- 27658827 TI - The transition from intra to extra-uterine life in late preterm infant: a single center study. AB - BACKGROUND: Infants born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse outcomes than those born at 37 weeks of gestation or later. Aim of this paper is to examine risk factors for late preterm births and to investigate the complications of the transition period in late preterm infants (LPIs). METHODS: All consecutive late preterm deliveries, excluded stillbirths, were included. Maternal and neonatal data, need for delivery room resuscitative procedures, temperature at birth (T1) and two hours after the admission (T2) were analyzed in all LPIs stratified by Gestational Age (GA) and divided into three groups (34, 35 and 36 weeks). RESULTS: Two hundred seventy-six LPIs were analyzed. Pregnancy complications were present in 72 mothers (26.1 %), more frequently at 34 weeks of gestation respect to 35 and 36 weeks (p = 0.008, p = 0.006 respectively). Forty seven LPIs (17.1 %) needed for any resuscitation and 37 (13.4 %) were ventilated at birth. LPIs at 34 weeks were significantly more likely to receive ventilation respect to those at 35 and 36. At T1 the mean temperature resulted lower at 34 weeks respect to 36 weeks (p = 0.03). At T2 respect to T1, the rate of normothermic neonates increased at 35 and 36 weeks (p = 0.003, p = 0.005, respectively). Hypoglicemia rate was similar among the groups; 66.7 % of hypoglicemic neonates were hypothermic at T1. The rate of respiratory diseases and NICU admission decreased with increasing GA. Higher number of neonates ventilated at birth developed respiratory disorders respect to those unventilated (40.5 % vs 8.4 %; p < 0.001). CONCLUSIONS: Transition period in LPIs may become critical, as resuscitation strategies can be required and heat loss can occur. LPIs, especially at 34 gestational weeks, are higher-risk group needing adequate and targeted management at birth. PMID- 27658828 TI - Pitfalls in anorexia nervosa research: The risk of artifacts linked to denial of illness and methods of preventing them. AB - One of the most serious problems faced by researchers studying eating disorders is denial of illness in individuals with anorexia nervosa. Importantly, the term "denial" not only has different meanings, but in the case of anorexia nervosa its very nature still remains obscure. It is not even known whether it is deliberate or unintentional. Denial of illness in anorexic patients has serious consequences for evaluation of the reliability of information obtained from those individuals. Indeed, the most frequently used screening questionnaires, such as the Eating Attitudes Test (EAT) (Garner & Garfinkel 1979) and the Eating Disorder Inventory (EDI) (Garner et al. 1983), may not reflect the psychological state of the subjects due to distorted responses. The objective of this review article is to elucidate, at least in part, the nature of denial of illness in anorexic individuals and, importantly, to present methods for direct or indirect measurement of this variable. The authors emphasize the detrimental effect of denial of illness on the quality of information obtained from the patients and the notorious unreliability of self-report data. The final part of the paper contains suggestions as to methods of bypassing the pitfalls associated with the influence of denial of illness on the results of studies involving anorexic individuals; for instance, it is recommended that one should build an honest and trustful relationship with the patient. Last but not least, the focus is placed on the potential of experimental psychology, which offers tools producing robust data, resistant to deliberate distortion by patients. PMID- 27658829 TI - Long-term Effects of Maternal Deprivation on the Volume, Number and Size of Neurons in the Amygdala and Nucleus Accumbens of Rats. AB - BACKGROUND: Maternal deprivation (MD) in rodents is an important neurodevelopmental model for studying a variety of behavioral changes which closely resemble the symptoms of schizophrenia in humans. SUBJECTS AND METHODS: To determine whether early-life stress leads to changes in the limbic system structures: the amygdala and the nucleus accumbens, 9-day-old Wistar rats were exposed to 24 hour MD. On P60 the rats were sacrificed for morphometric analysis and their brains were compared to the control group. RESULTS: Results show that MD affected important limbic system structures: the amygdala and the nucleus accumbens, whose volume was decreased (17% of the control value for the amygdala and 9% of the control value for the nucleus accumbens ), as well as the number of neurons (41% of the control value for the amygdala and 43% of the control value for the nucleus accumbens ) and the size of their cells soma (12% of the control value for the amygdala and 33% of the control value for the nucleus accumbens ). CONCLUSION: This study indicates that early stress in life leads to changes in the morphology of the limbic areas of the brain, most probably due to the loss of neurons during postnatal development, and it further contributes to our understanding of the effects of maternal deprivation on brain development. PMID- 27658830 TI - The association of pineal gland volume and body mass in obese and normal weight individuals: a pilot study. AB - BACKGROUND: In obese individuals impaired sleep and neuroendocrine alterations such as melatonin deficits are associated with circadian rhythm disruption, altered circadian clock gene expression, and bright light at night. While the relation of pineal gland volume (PGV) and melatonin levels has recently been documented in humans, surprisingly little is known about the possible interference of the PGV and the pathophysiology of obesity in humans. SUBJECTS AND METHODS: We therefore compared the PGV of obese with non-obese individuals; both groups were matched by age and gender. Volumetric analyses were performed on the basis of 3 Tesla high resolution Magnetic Resonance Imaging (MRI). RESULTS: We found, that the PGV was significantly smaller in obese individuals than in lean controls (P=0.036). Moreover, PGV and waist-hip ratio showed a significant negative association in controls (P=0.018, rs=-0.602) whereas no association of both variables was found in obese individuals (P=0.856, rs=-0.051). CONCLUSIONS: Thus, the current pilot investigation suggests that pineal gland function, reflected by PGV might be involved in the energy homeostasis and pathophysiological mechanisms that contribute to the development and the maintenance of obesity in humans. Moreover, our data supports the notion that the replacement of melatonin deficits might be a novel strategy in the treatment of obesity. PMID- 27658831 TI - Sensory gating deficits and impaired quality of life in patients with schizophrenia: A preliminary study. AB - BACKGROUND: New determinants of quality of life in schizophrenia need to be identified. As sensory gating deficit is core impairment in schizophrenia, the present study hypothesized that sensory gating deficit is a determinant of impaired quality of life in schizophrenia. This study therefore investigated the relationship between sensory gating deficit and quality of life in patients with schizophrenia after adjusting for key confounding factors. SUBJECTS AND METHODS: Sensory gating was assessed with the auditory event-related potential method by measuring P50 amplitude changes in a double-click conditioning-testing procedure, perceptual impairments related to sensory gating deficit was assessed with the SGI questionnaire and quality of life was assessed with the SQoL 18 questionnaire in 39 patients with schizophrenia. RESULTS: Patients with sensory gating deficit (n=14) had a lower subjective quality of life on the psychological well-being dimension evaluated with SQoL 18 questionnaire (p=0.008) compared to those without it (n=25). This result remained significant (B=-0.45, Wald=4.84, p=0.02) after taking into account 7 potential confounding factors (gender, age, level of education, duration of disorder, positive symptoms, depressive symptoms and anxiety symptoms). Poorer psychological well-being was related to a higher score on the SGI (rho=-0.40, p=0.01), in particular on the Distractibility dimension (rho=-0.47, p=0.001). CONCLUSIONS: These findings suggest that sensory gating deficit may be a determinant of impaired quality of life in schizophrenia. Further studies are needed to address the causal relationship between sensory gating deficit, perceptual impairments, attentional deficit and impaired quality of life in schizophrenia in order to act more efficiently on the quality of life of patients with this disorder. PMID- 27658832 TI - Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries. AB - OBJECTIVE: The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. METHODS: Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. RESULTS: 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). CONCLUSION: Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries. Given that results are from the first large-scale analysis of RWD, we believe these findings can be a benchmark for future real-world studies, which could contribute to the optimization of treatment for this debilitating disease. PMID- 27658834 TI - The Effect of Antipsychotics on Bone Mineral Density and Sex Hormones in Male Patients with Schizophrenia. AB - BACKGROUND: The aim of this study was to compare the bone mineral density (BMD) of male schizophrenia patients with those of healthy controls in order to determine the relationship between BMD and hormonal changes. SUBJECTS AND METHODS: The study sample included male outpatients between 18 and 55 years old, diagnosed with schizophrenia who had used prolactin-raising antipsychotics (n=23) and prolactin-sparing antipsychotics (n=19) for at least twelve months, along with an age - matched healthy control group. A socio-demographic form was administered, BMD and T-score measurements were performed with a DEXA test, and hormone levels were measured with commercial test kits. RESULTS: The prolactin levels of the prolactin-raising group (PRG) were significantly higher than those of the healthy control group (CG) and the prolactin-sparing group (PSG). While prolactin levels were normal in the CG, hyperprolactinemia was found in 15.8% (n=3) of patients in the PSG and 65.2% (n=15) of subjects in the PRG. Estradiol levels for the PRG and PSG were similar but significantly lower than those of the CG. There was a statistically significant difference between the PRG, PSG and CG in terms of their L1-4 total actual bone density and T-scores. BMD and T-scores were lower for the PRG in comparison with the PSG and CG, and were consistent with osteopenia. Although not observed for every tested region, a negative correlation was found between age, duration of therapy, duration of illness, and T-scores. A positive correlation was found between subjects BMI and T-scores. A consistent negative correlation was found between total testosterone and L1-4 total T-scores when corrected according to prolactin and estradiol. A linear regression analysis found significant relationships between age, BMI, duration of therapy, duration of illness, chlorpromazine equivalent dose, estradiol and testosterone affected T-scores for some regions. CONCLUSIONS: The long-term use of prolactin - raising antipsychotic medications as well as hyperprolactinemia and hypoestrogenism accelerate bone degradation. PMID- 27658833 TI - Antipsychotic treatment, prolactin, and breast tumorigenesis. AB - BACKGROUND: Over the last decades prolactin (PRL) has gained attention for its possible role in breast tumorigenesis. As all antipsychotics (although differences with respect to PRL elevation are large) have the propensity to induce hyperprolactinemia (HPRL), questions have arisen concerning the influence of PRL-elevating antipsychotic medications on breast cancer risk. SUBJECTS AND METHODS: A literature search (until January 2016), using the MEDLINE database, was conducted for English-language published clinical studies to identify and synthesize data of the current state of knowledge concerning the relationship between HPRL, breast cancer risk (factors) and antipsychotic medication. RESULTS: Results of human prospective studies evaluating the relationship between pre diagnostic circulating PRL levels and breast cancer risk are limited, equivocal and only correlational. Associations between higher circulating PRL levels and other breast cancer risk factors than nulliparity and hormone therapies mostly have been negative for both pre-and postmenopausal women. Until today, no causal link between (chronic) administration of antipsychotics and breast tumorigenesis in humans has been demonstrated. Finally, several reports describe mechanisms of cancer protection with the PRL hormone as well as with antipsychotic medication. CONCLUSION: The role of PRL in breast carcinogenesis therefore remains unclear, unconfirmed, yet controversial. Antipsychotics should not be withhold for breast cancer prevention reasons to patients in need of this sometimes life-saving medication, even if classical breast cancer risk factors are present. PMID- 27658835 TI - Remission and employment status in schizophrenia and other psychoses: One-year prospective study in Croatian patients treated with risperidone long acting injection. AB - BACKGROUND: While numerous studies have confirmed the efficacy of risperidone long-acting injectable (RLAI) on many clinical outcomes in patients with schizophrenia, there is no data regarding its influence on employment status. SUBJECT AND METHODS: This was a 12-month observational study with flexible doses of RLAI on a Croatian population of patients with schizophrenia and other psychoses. Visits were at baseline and after 1, 3, 6 and 12 months of treatment. Treatment response was evaluated using Clinical Global Impression of Illness Severity (CGI-S) and Improvement (CGI-I) scales, while remission was defined by 8 items of Positive and Negative Syndrome Scale (PANSS). Employment status was determined at baseline and at study endpoint. RESULTS: A total of 362 patients were included, with a median age of 37 (interquartile range 29-47) years, 63.5 % were males and 67.4% were hospitalised at baseline. Overall 258 (71.3%) patients completed the study. Improvements in CGI-S scores from baseline were significant (p<0.001) at all visits. Remission criteria were met in 9 (2.5%) patients at baseline, and in 199 (54.9%) at endpoint, while 144 patients (52.7%) achieved symptomatic remission. Female patients were five times more likely to achieve symptomatic remission (OR=5.2; 95%CI=2.64-10.19). At baseline, 74/362 (20.4%) patients were employed, compared to 77/257 (30.0%) at endpoint (p<0.001). Adverse events were spontaneously reported in 55 (15.2%) patients. Three patients died (judged not to be related to RLAI) and one patient committed homicide. CONCLUSIONS: Patients treated with RLAI had significant improvements in CGI-S scale scores, hospitalization status, rates of remission and employment status, indicating the benefits of continuous treatment over time. Further studies on the comparative impact of different treatment strategies on functional recovery are needed. PMID- 27658836 TI - Attitudes of Croatian psychiatrists towards long-acting injectable antipsychotics. AB - BACKGROUND: Despite many advantages of long-acting injectable antipsychotics (LAIA), this type of therapy is still underused in routine practice. Since psychiatrists' attitudes play an important role in prescription rate of LAIA, we found it valuable to examine their attitudes because, according to our knowledge, there hasn't been similar research in Croatia so far. SUBJECTS AND METHODS: In this research, we included the total of 48 psychiatrists. For research purposes, we created a questionnaire modeled on standardized questionnaire. Results are described with descriptive statistics and Likert scale was used to measure respondents' attitudes to statements. RESULTS: The number of years of their experience in practice is expressed with median of 13.50 years with minimal value of 1.00 and maximum value of 36.00 years. Most of psychiatrists find that LAIA play an important role in treatment of schizophrenia (n=44, 93.62%) and that they tend to prescribe that type of therapy (n=39, 81.25%). Almost all of psychiatrists (n=45, 93.75%) agree or strongly agree that it is easier to control patients' disease if they are treated with LAIA rather than with oral therapy and 32 of them (68.08%) think that doctor-patient relationship is more successful when patients are treated with LAIA than with oral antipsychotics. According to their experience (n=32, 68.08%) patients prefer to be treated with oral antipsychotics instead of LAIA. We expressed approximate percentage of their patients treated with LAIA with median of 20%, with minimum value of 0.00% and maximum value of 70.00%. CONCLUSION: According to the results of our research, attitudes of psychiatrists towards LAIA are mostly positive, but considering the fact that there is a small number of their patients who are treated with them, we emphasize that psychiatrists still prescribe oral antipsychotics much more often than LAIA. Despite positive attitudes of patients towards LAIA, majority of psychiatrists think that patients would rather choose oral therapy. PMID- 27658837 TI - Attitudes of Croatian patients with severe mental illness towards long-acting injectable antipsychotics. AB - BACKGROUND: It has been shown that patients' attitudes towards long-acting injectable antipsychotics (LAIA) have the influence on the acceptance and use of this type of therapy. The aim of our study was to explore attitudes of patients because, according to our knowledge, there has been no similar research in Croatia thus far. SUBJECTS AND METHODS: Two questionnaires were given to the total of 100 patients, the first one to patients treated with LAIA (group 1) and the second one to patients treated with oral antipsychotics (group 2). RESULTS: Significantly more patients treated with LAIA find that good aspects of their medication outweigh the bad (p=0.014). Almost one third of patients treated with oral antipsychotics (n=16, 32%) quit taking medication when they feel better and 6 patients (12%) very often or often forget to take medication. Larger number of patients treated with LAIA feels much better since they have been taking their medication (group 1=82%, group 2=68%). Almost all patients treated with LAIA would recommend their therapy to other patients (92%), which is not the case with patients treated with oral antipsychotics (58%). 90% of patients decided to take LAIA because of suggestion given by their psychiatrists and 10% were persuaded by their psychiatrists. When given potential advantages of LAIA, 84% of patients said they found very positive the fact that they didn't have to think about taking their medication every day, 82% were fond of LAIA's simplicity, 68% considered positive that their psychiatrists had better control over their treatment and 66% were very content with their recovery. CONCLUSION: The larger number of patients treated with LAIA is content with their therapy than patients treated with oral antipsychotics. Patients' attitudes have changed in a way that they don't find LAIA coercive anymore and most of them agreed to that type of therapy on a suggestion given by their psychiatrists. PMID- 27658838 TI - Somatic comorbidities are independently associated with the poor health-related quality of life in psychiatric patients. AB - BACKGROUND: Despite the increased risk, the quality of somatic healthcare is lower for patients with mental illnesses. Currently dominant approach separates physical and mental, primary and secondary healthcare. Objective of our study was to explore whether somatic comorbidities are associated with a poor HRQoL independently of some sociodemographic and clinical factors. Majority of studies have explored particular somatic and psychiatric illnesses. Therefore we decided to access the problem from the general perspective of the universe of somatic and mental illnesses in the large psychiatric institution. SUBJECTS AND METHODS: This nested cross-sectional study was done during May 2016 at Psychiatric hospital Sveti Ivan, Zagreb, Croatia on the sample of 506 patients diagnosed with psychiatric illnesses (ICD-10: F00-F99). Key outcome was the lowest 25% results on the SF-36 General health sub-scale, indicating the worst HRQoL. Predictors were all detected somatic illnesses. By multivariate logistic regression we controlled different sociodemographic, vital and clinical factors. RESULTS: After adjustment for different sociodemographic and clinical factors, three somatic comorbidities remained independently associated with the worst HRQoL: endocrine, nutritional and metabolic diseases (E00-E90), diseases of respiratory system (J00 J99) and diseases of musculoskeletal system and connective tissue (M00-M99) CONCLUSIONS: Somatic comorbidities in psychiatric patients are associated with the poor HRQoL independently of different sociodemographic, vital and clinical factors and they should be treated seriously and integrally with mental aspects of HRQoL. Early comorbidities detection and adequate pharmacological and psychotherapeutic treatment, as well as the prevention of risk factors, may improve the quality of life and reduce morbidity and mortality of psychiatric patients. PMID- 27658840 TI - Olanzapine induced stuttering: a case report. PMID- 27658842 TI - [The beta draft of the ICD-11 chapter on mental and behavioural disorders]. PMID- 27658841 TI - Acute psychosis - anti-NMDA receptor encephalitis phase. PMID- 27658839 TI - Serum concentrations of TNF-alpha and its soluble receptors during psychotherapy in German soldiers suffering from combat-related PTSD. AB - BACKGROUND: Changes in serum concentrations of tumor necrosis factor-alpha (TNF alpha) and its soluble receptors (sTNF-R) p55 and p75 have been shown to be associated with various psychiatric treatments. SUBJECTS AND METHODS: Before and after treatment, serum levels of TNF-alpha, sTNF-R p55 and sTNF-R p75 were measured in 38 German soldiers who had been deployed abroad and suffered from combat-related post-traumatic stress disorder (PTSD). Patients were randomized either to inpatient psychotherapy (N=21) including eye movement desensitization and reprocessing (EMDR) or to outpatient clinical management (N=17). Symptoms of PTSD were measured using the Post-traumatic Stress Diagnostic Scale (PDS). RESULTS: The PDS score significantly decreased across time in both groups. Serum concentrations of TNF-alpha increased, while sTNF-R p55 and sTNF-R p75 levels decreased significantly. After the treatment period, we could not detect any significant difference regarding TNF-alpha, sTNF-R p55 or sTNF-R p75 levels between the inpatient psychotherapy group and the outpatient clinical management control group. CONCLUSIONS: This relatively small clinical study suggests that specific inpatient psychotherapy but also non-specific supportive outpatient treatment for PTSD are associated with changes in the TNF-alpha system. This may represent an immunological effects or side effects of psychotherapy. PMID- 27658843 TI - Narcissistic personality disorder and suicide. PMID- 27658844 TI - Device Strategies for Patients in INTERMACS Profiles 1 and 2 Cardiogenic Shock: Double Bridge With Extracorporeal Membrane Oxygenation and Initial Implant of More Durable Devices. AB - For Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 and 2 cardiogenic shock patients initially placed on extracorporeal membrane oxygenation (ECMO), whether crossover to more durable devices is associated with increased survival, and its optimal timing, are not established. Profiles 1 and 2 patients placed on mechanical support were prospectively registered. Survival and successful hospital discharge were compared between patients placed on ECMO only, ECMO with early crossover, and ECMO with delayed crossover. Survival of patients directly implanted with non-ECMO devices was also reported. One-hundred and sixty two patients were included. Mean age was 52.2 +/- 13.8 years. Seventy-three of 162 (45.1%) were initiated on ECMO. Of these, 43 were supported with ECMO only, 11 were crossed-over early <4 days, and 19 were crossed-over in a delayed fashion. Survival was different across groups (Log-rank P < 0.002). In multivariate analysis, early crossover was associated with decreased mortality as compared with no crossover (hazard ratio [HR] 0.201, 95% confidence interval [95%CI] 0.058-0.697, P = 0.011) or with delayed crossover (HR 0.255, 95%CI 0.073 0.894, P = 0.033). Mortality was not different between delayed crossover and no crossover (P = 0.473). In patients with early crossover there were no deaths at 30 days, and 60-day survival was 90.0 +/- 9.5%. Survival to hospital discharge was 72.8%. For patients directly implanted with non-ECMO devices, 30-day and 60 day survival was 90.9 +/- 3.1% and 87.3 +/- 3.8%, respectively, and survival to hospital discharge was 78.7%. Both initial implant of durable devices and double bridge strategy was associated with improved outcomes. If the double bridge strategy is chosen, early crossover is associated with improved survival and successful hospital discharge. PMID- 27658845 TI - Diversity distribution patterns of Chinese endemic seed plant species and their implications for conservation planning. AB - Endemism is an important concept in biogeography and biodiversity conservation. China is one of the richest countries in biodiversity, with very high levels of plant endemism. In this study, we analysed the distribution patterns of diversity, the degree of differentiation, and the endemicity of Chinese endemic seed plants using the floristic unit as a basic spatial analysis unit and 11 indices. The analysis was based on distribution data of 24,951 native seed plant species (excluding subspecies and varieties) and 12,980 Chinese endemic seed plant species, which were sourced from both specimen records and published references. The distribution patterns of Chinese endemic flora were generally consistent but disproportionate across China for diversity, degree of differentiation and endemicity. The South Hengduan Mountains Subregion had the highest values for all indices. At the regional level, both the Hengduan Mountains and the Central China regions were highest in diversity and degrees of differentiation. However, both the rate of local endemic to native species and the rate of local to Chinese endemic species were highest in the Taiwan Region and the South Taiwan Region. The Hengduan Mountains Region and the Central China Region are two key conservation priority areas for Chinese endemic seed plants. PMID- 27658847 TI - Synthesis, peptoids and yellow pseudo peptides. PMID- 27658846 TI - The replicability of cannabis use prevalence estimates in the United States. AB - Recent changes in cannabis policy in the United States have prompted increased interest in cannabis use estimates, and replicability of these estimates. Here, we compare prevalence estimates from two concurrent approaches: (1) standard social survey with audio computer-assisted self-interviews at respondent's home (ACASI-H), derived from the National Surveys on Drug Use and Health (NSDUH), and (2) standard health survey with ACASI assessment in a mobile health examination vehicle (ACASI-M), derived from National Health and Nutrition Examination Surveys (NHANES), 2005-2012, with essentially the same standardized items in cannabis modules. NHANES ACASI-M prevalence proportions for recently-active-cannabis-use are an estimated 130-140% larger than corresponding NSDUH ACASI-H estimates (p < 0.05). In exploratory stratified analyses, we sought to understand these NHANES NSDUH differences, and found no differences in lifetime-history-of-cannabis-use. However, for participants living with others in the same residence, moving cannabis assessment out of the dwelling unit might promote larger recently-active cannabis-use estimates; no NHANES-NSDUH differences were found for participants living alone. The observed discrepancies might be non-ignorable in a policy or program evaluation context. A methods research program will be needed to account for between-survey differences of the type observed here, perhaps with a focus on within-residence versus non-residence assessment as a source of variation. PMID- 27658848 TI - Hazardous thunderstorm intensification over Lake Victoria. AB - Weather extremes have harmful impacts on communities around Lake Victoria, where thousands of fishermen die every year because of intense night-time thunderstorms. Yet how these thunderstorms will evolve in a future warmer climate is still unknown. Here we show that Lake Victoria is projected to be a hotspot of future extreme precipitation intensification by using new satellite-based observations, a high-resolution climate projection for the African Great Lakes and coarser-scale ensemble projections. Land precipitation on the previous day exerts a control on night-time occurrence of extremes on the lake by enhancing atmospheric convergence (74%) and moisture availability (26%). The future increase in extremes over Lake Victoria is about twice as large relative to surrounding land under a high-emission scenario, as only over-lake moisture advection is high enough to sustain Clausius-Clapeyron scaling. Our results highlight a major hazard associated with climate change over East Africa and underline the need for high-resolution projections to assess local climate change. PMID- 27658849 TI - Predator-prey interactions in the plankton: larval fish feeding on evasive copepods. AB - Capture success and prey selectivity were investigated in clownfish Amphiprion ocellaris larvae using videography. Three prey types were tested using developmental stages (nauplii, copepodites and adults) of the copepod Parvocalanus crassirostris. Predatory abilities improved rapidly between days 1 and 14 post-hatch. Initially, capture success was limited to nauplii with few attacks on larger stages. Captures of copepodites were first observed at 3 dph, and of adults at 8 dph. Consistent strikes at the larger prey were observed on the day prior to successful captures (2 dph for copepodites, 7 dph for adults). Difference in capture success between nauplii and adults at 8 dph was an order of magnitude. Differences in capture success among prey types persisted but decreased to three-fold by 14 dph. Younger A. ocellaris attacked nauplii preferentially and avoided adult prey. Strike selectivity declined with age, and no selectivity was observed after 10 dph. However, numerically 50% of the ingested prey were still nauplii at 14 dph under the experimental conditions. PMID- 27658850 TI - Enhanced superconductivity in aluminum-based hyperbolic metamaterials. AB - One of the most important goals of condensed matter physics is materials by design, i.e. the ability to reliably predict and design materials with a set of desired properties. A striking example is the deterministic enhancement of the superconducting properties of materials. Recent experiments have demonstrated that the metamaterial approach is capable of achieving this goal, such as tripling the critical temperature TC in Al-Al2O3 epsilon near zero (ENZ) core shell metamaterial superconductors. Here, we demonstrate that an Al/Al2O3 hyperbolic metamaterial geometry is capable of a similar TC enhancement, while having superior transport and magnetic properties compared to the core-shell metamaterial superconductors. PMID- 27658851 TI - Identification of disease states associated with coagulopathy in trauma. AB - BACKGROUND: Trauma is the leading cause of death between the ages of 1 to 44 in the United States. Blood loss is the primary cause of these deaths. The discrimination of states through which patients transition would be helpful in understanding the disease process, and in identification of critical states and appropriate interventions. Even though these states are strongly associated with patients' blood composition data, there has not been a way to directly identify them. Statistical tools such as hidden Markov models can be used to infer the discrete latent states from the blood composition data. METHODS: We applied a hidden Markov model to time-series multivariate patient measurements from the UCSF/ San Francisco General Hospital and Trauma Center. Ten blood factor related measurements were used to identify the model: factors II, V, VII, VIII, IX, X, antithrombin III, protein C, prothrombin time and partial thromboplastin time. Missing data in the time-series dataset was considered in the hidden Markov model. The number of states was determined by minimizing the Bayesian information criterion across different numbers of states. RESULTS: After preprocessing, 1090 patients with a total number of 2176 time point measurements were included in the analysis. The hidden Markov model identified 6 disease states and 3 stages. We analyzed their relationships to the blood composition data and the coagulation cascade. The states are very indicative of the disease progression status of patients. CONCLUSIONS: Six disease states and 3 stages associated with Coagulopathy in trauma were identified in our study. The hidden Markov model can be useful in identifying latent states by using patients' time-series multivariate data. The information obtained from the states and stages can be useful in the clinical setting. PMID- 27658855 TI - UiO-66-Type Metal-Organic Framework with Free Carboxylic Acid: Versatile Adsorbents via H-bond for Both Aqueous and Nonaqueous Phases. AB - The metal-organic framework (MOF) UiO-66 was synthesized in one step from zirconium chloride and isophthalic acid (IPA), together with the usual link material, terephthalic acid (TPA). UiO-66 with free -COOH can be obtained in a facile way by replacing up to 30% of the TPA with IPA. However, the chemical and thermal stability of the synthesized MOFs decreased with increasing IPA content used in the syntheses, suggesting an increase in the population of imperfect bonds in the MOFs because of the asymmetrical structure of IPA. The obtained MOFs with free -COOH were applied in liquid-phase adsorptions from both water and model fuel to not only estimate the potential applications but also confirm the presence of -COOH in the MOFs. The adsorbed amounts of several organics (triclosan and oxybenzone from water and indole and pyrrole from fuel) increased monotonously with increasing IPA content applied in MOF synthesis (or -COOH in the MOFs). The favorable contribution of free -COOH to adsorption can be explained by H-bonding, and the direction of H-bonds (adsorbates: H donor; MOFs: H acceptor) was confirmed by the adsorption of oxybenzone in a wide pH range. The versatile applications of the MOFs with -COOH in adsorptions from both polar and nonpolar phases are remarkable considering that hydrophobic and hydrophilic adsorbents are generally required for water and fuel purification, respectively. Finally, the presence of free -COOH in the MOFs was confirmed by liquid-phase adsorptions together with general Fourier transform infrared analyses and decreased chemical and thermal stability. PMID- 27658854 TI - Elemental characterisation of melanin in feathers via synchrotron X-ray imaging and absorption spectroscopy. AB - Melanin is a critical component of biological systems, but the exact chemistry of melanin is still imprecisely known. This is partly due to melanin's complex heterogeneous nature and partly because many studies use synthetic analogues and/or pigments extracted from their natural biological setting, which may display important differences from endogenous pigments. Here we demonstrate how synchrotron X-ray analyses can non-destructively characterise the elements associated with melanin pigment in situ within extant feathers. Elemental imaging shows that the distributions of Ca, Cu and Zn are almost exclusively controlled by melanin pigment distribution. X-ray absorption spectroscopy demonstrates that the atomic coordination of zinc and sulfur is different within eumelanised regions compared to pheomelanised regions. This not only impacts our fundamental understanding of pigmentation in extant organisms but also provides a significant contribution to the evidence-based colour palette available for reconstructing the appearance of fossil organisms. PMID- 27658852 TI - Pathophysiological and diagnostic implications of cortical dysfunction in ALS. AB - Cortical dysfunction - specifically, the development of hyperexcitability - seems to be an early and intrinsic feature of sporadic and familial amyotrophic lateral sclerosis (ALS) phenotypes, preceding the onset of lower motor neuron dysfunction and correlating with ensuing lower motor neuron dysfunction and degeneration. In fact, cortical dysfunction could provide a pathogenic basis for ALS, with corticomotor neuronal hyperexcitability mediating motor neuron degeneration via a trans-synaptic, glutamate-mediated, excitotoxic mechanism. The recent identification of C9orf72 repeat expansion as an important genetic risk factor for both ALS and frontotemporal dementia has underscored the importance of cortical function in ALS pathogenesis, and has helped to confirm that the disease forms part of a spectrum of central neurodegenerative processes. Changes in cortical function that develop in ALS could prove useful as diagnostic biomarkers, potentially enhancing the diagnosis of ALS at an early stage of the disease process. Pathophysiological and diagnostic biomarkers of cortical function might also provide insights to guide the development of future therapeutic approaches, including stem cell and genetic interventions, thereby providing potential for more-effective management of patients with ALS. PMID- 27658853 TI - Sweeter and stronger: enhancing sweetness and stability of the single chain monellin MNEI through molecular design. AB - Sweet proteins are a family of proteins with no structure or sequence homology, able to elicit a sweet sensation in humans through their interaction with the dimeric T1R2-T1R3 sweet receptor. In particular, monellin and its single chain derivative (MNEI) are among the sweetest proteins known to men. Starting from a careful analysis of the surface electrostatic potentials, we have designed new mutants of MNEI with enhanced sweetness. Then, we have included in the most promising variant the stabilising mutation E23Q, obtaining a construct with enhanced performances, which combines extreme sweetness to high, pH-independent, thermal stability. The resulting mutant, with a sweetness threshold of only 0.28 mg/L (25 nM) is the strongest sweetener known to date. All the new proteins have been produced and purified and the structures of the most powerful mutants have been solved by X-ray crystallography. Docking studies have then confirmed the rationale of their interaction with the human sweet receptor, hinting at a previously unpredicted role of plasticity in said interaction. PMID- 27658856 TI - Eradication of infection, survival, and radiological results of uncemented revision stems in infected total hip arthroplasties. AB - Background and purpose - The use of uncemented revision stems is an established option in 2-stage procedures in patients with periprosthetic joint infection (PJI) after total hip arthroplasty (THA). However, in 1-stage procedures, they are still rarely used. There are still no detailed data on radiological outcome after uncemented 1-stage revisions. We assessed (1) the clinical outcome, including reoperation due to persistent infection and any other reoperation, and (2) the radiological outcome after 1- and 2-stage revision, using an uncemented stem. Patients and methods - Between January 1993 and December 2012, an uncemented revision stem was used in 81 THAs revised for PJI. Patients were treated with 1- or 2-stage procedures according to a well-defined algorithm (1 stage: n = 28; 2-stage: n = 53). All hips had a clinical and radiological follow up. Outcome parameters were eradication of infection, re-revision of the stem, and radiological changes. Survival was calculated using Kaplan-Meier analysis. Radiographs were analyzed for bone restoration and signs of loosening. The mean clinical follow-up time was 7 (2-15) years. Results - The 7-year infection-free survival was 96% (95% CI: 92-100), 100% for 1-stage revision and 94% for 2-stage revision (95% CI: 87-100) (p = 0.2). The 7-year survival for aseptic loosening of the stem was 97% (95% CI: 93-100), 97% for 1-stage revision (95% CI: 90-100) and 97% for 2-stage revision (95% CI: 92-100) (p = 0.3). No further infection or aseptic loosening occurred later than 7 years postoperatively. The radiographic results were similar for 1- and 2-stage procedures. Interpretation - Surgical management of PJI with stratification to 1- or 2-stage exchange according to a well-defined algorithm combined with antibiotic treatment allows the safe use of uncemented revision stems. Eradication of infection can be achieved in most cases, and medium- and long-term results appear to be comparable to those for revisions for aseptic loosening. PMID- 27658858 TI - Magnetic interactions in compositionally modulated nanowire arrays. AB - Series of high hexagonally ordered compositionally modulated nanowire arrays, with different Cu layer and FeCoCu segment thicknesses and a constant diameter of 35 nm, were fabricated by electroplating from a single electrolytic bath into anodic aluminum oxide membranes. The objective of the study was to determine the influence of ferromagnetic (FM) segment and non-ferromagnetic (NFM) layer thickness on the magnetic properties, particularly coercivity and magnetic interactions. First-order reversal curve (FORC) measurements and simulations were performed to quantify the effect of the inter-/intra-nanowire magnetostatic interactions on the coercivity and interaction field distributions. The FORC coercivity increases for a thick NFM layer and long FM segments due to decoupling of the the FM segments and the increased shape anisotropy, respectively. On the other hand, the interaction field presents a parallel strong reduction for a thick NFM layer and thin FM segments, which is ascribed to a similar NFM/FM thickness ratio and degree of FM segment decoupling along the nanowire. PMID- 27658859 TI - Stereospecific Synthesis of Tetrahydronaphtho[2,3-b]furans Enabled by a Nickel Promoted Tandem Reductive Cyclization. AB - A Ni-mediated cascade to a stereoselective synthesis of trans tetrahydronaphtho[2,3-b]furans is efficiently achieved for the first time. The mild reductive system can be easily generated from inexpensive and air-stable materials and shows a broad positional tolerance of substituents that were previously difficult or impossible to access by other methods. Facile syntheses toward new analogues of therapeutic agents (iso)deoxypodophyllotoxin are also reported. In addition, the inherent substrate control is disclosed for the observed unique stereoselectivities during cyclizations. PMID- 27658860 TI - Citrobacter braakii Bacteremia: Case Report and Review of the Literature. AB - Bacteremia is frequently caused by gram-positive organisms such as Staphylococcus aureus or beta hemolytic streptococci. While there is adequate information for the diagnosis and management of these common bacteria, less information is available to address bacteremia that is caused by uncommon bacteria such as Citrobacter. Citrobacter species are gram-negative bacilli that have been noted to cause infections in immune compromised patients. The re-speciation of Citrobacter by its varied genetic composition has produced 11 distinct species. While C. braakii is part of the genome species 6 of the previous Citrobacter freundii complex, there is a lack of definitive research on the subject of Citrobacter bacteremia caused by lesser- known species. We report an unusual case of Citrobacter braakii bacteremia in a patient with multiple comorbidities that presented to the hospital with cellulitis and pleural effusion. Blood cultures grew Citrobacter braakii. Despite good response to antibiotic treatment, the patient's infection proved to be persistent and he succumbed to the cirrhosis of the liver and subsequent renal failure. Multiple and fatal underlying disease processes seem to worsen the likelihood of recovery from unusual infections. We believe our case report can add to the limited data available for C. braakii. PMID- 27658857 TI - The genetic and epigenetic landscapes of the epithelium in asthma. AB - Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium. Epigenetic factors that regulate airway epithelial structure and function are also an attractive area for assessment of susceptibility to asthma. In this review we provide a comprehensive discussion on genetic factors; from using linkage designs and candidate gene association studies to genome-wide association studies and whole genome sequencing, and epigenetic factors; DNA methylation, histone modifications, and non-coding RNAs (especially microRNAs), in airway epithelial cells that are functionally associated with asthma pathogenesis. Our aims were to introduce potential predictors or therapeutic targets for asthma in airway epithelium. Overall, we found very small overlap in asthma susceptibility genes identified with different technologies. Some potential biomarkers are IRAKM, PCDH1, ORMDL3/GSDMB, IL-33, CDHR3 and CST1 in airway epithelial cells. Recent studies on epigenetic regulatory factors have further provided novel insights to the field, particularly their effect on regulation of some of the asthma susceptibility genes (e.g. methylation of ADAM33). Among the epigenetic regulatory mechanisms, microRNA networks have been shown to regulate a major portion of post transcriptional gene regulation. Particularly, miR-19a may have some therapeutic potential. PMID- 27658861 TI - Successful treatment of extranodal natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis with MEDA chemotherapy. PMID- 27658862 TI - CBT for depression and drug adherence in HIV care. PMID- 27658863 TI - Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. AB - BACKGROUND: Immune priming before reversal of latency might be a component of a functional HIV cure. To assess this concept, we assessed if therapeutic HIV immunisation followed by latency reversal would affect measures of viral transcription, plasma viraemia, and reservoir size in patients with HIV on suppressive antiretroviral therapy. METHODS: In this single-arm, phase 1B/2A trial, we recruited adults treated at the Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark (aged >=18 years) with successfully treated HIV-1 with plasma RNA loads of less than 50 copies per mL for the previous year and CD4 counts of at least 500 cells per MUL. Exclusion criteria included CD4 counts of less than 200 cells per MUL within the past 2 years, active hepatitis B or C infections, and clinically significant cardiac disease, including QTc prolongation. Participants received six therapeutic intradermal HIV 1 immunisations with 12 mg/mL Vacc-4x and 0.6 mg/mL rhuGM-CSF over 12 weeks (at 0 weeks, 1 week, 2 weeks, 3 weeks, 11 weeks, and 12 weeks) before receiving 5 mg/m(2) intravenous romidepsin once a week for 3 weeks. This procedure was followed by analytical treatment interruption. Coprimary outcomes were changes in copies of HIV-1 DNA (total and integrated) per million CD4 T cells and infectious units per million (IUPM) resting memory CD4 T cells established by viral outgrowth, assessed in all patients receiving at least one dose of active treatment with assessable data. We assessed total HIV-1 DNA at screening, before romidepsin treatment, and 6 weeks after romidepsin treatment. We assessed integrated viral DNA at baseline, before romidepsin treatment, and 8 weeks after romidepsin treatment. We assessed IUPM at screening, 2 weeks before romidepsin treatment, and 6 weeks after romidepsin treatment. This trial is registered at ClinicalTrials.gov, number NCT02092116. FINDINGS: Between May 19, 2014, and Oct 8, 2014, we enrolled 20 individuals, of whom 17 completed all Vacc-4x and rhuGM CSF administrations and romidepsin infusions. 16 of 17 had assessable total HIV-1 DNA, 15 of 17 had assessable integrated HIV-1 DNA, and six of 17 had assessable IUPM at baseline and at one or more timepoints after study treatment. Total HIV-1 DNA declined from screening to 6 weeks after romidepsin treatment (mean reduction 39.7%, 95% CI -59.7 to -11.5; p=0.012). The decrease in integrated HIV-1 DNA from baseline to 8 weeks after romidepsin treatment was not significant (19.2%, -38.6 to 6.3; p=0.123). Among the six assessable participants, the mean reduction in IUPM from screening to 6 weeks after romidepsin treatment was 38.0% (95% CI -67.0 to -8.0; p=0.019). Of 141 adverse events, 134 (95%) were grade 1 and seven (5%) were grade 2-3. INTERPRETATION: This in-vivo combinatorial approach provides the first evidence for the feasibility of a combined shock and kill strategy, but also emphasises that further optimisation of this strategy is needed to achieve a sizeable effect on the latent reservoir that will translate into clinically measurable benefits for people living with HIV-1. FUNDING: Bionor Pharma, the Research Council of Norway, and SkatteFUNN. PMID- 27658865 TI - When is a PrEP candidate ready for phase 3? PMID- 27658864 TI - Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment. AB - BACKGROUND: Long-acting injectable antiretroviral agents are being developed for HIV-1 prevention. The MWRI-01 study was done to characterise the safety, acceptability, and pharmacokinetic and pharmacodynamic profile of long-acting rilpivirine. METHODS: We did a phase 1 open-label study at the University of Pittsburgh. We enrolled healthy individuals (aged 18-45 years) who were seronegative for HIV-1. Participants were assigned alternately one intramuscular dose of either 1200 mg or 600 mg long-acting rilpivirine, beginning with the 1200 mg dose. We obtained plasma specimens, genital and rectal fluids, and tissue samples (rectal, cervical, and vaginal) before and after exposure to long-acting rilpivirine for assessment of pharmacokinetics and ex-vivo biopsy challenge with HIV-1. Our primary objective was to characterise product safety, and the analysis included all enrolled participants. This trial is registered with ClinicalTrials.gov, number NCT01656018. FINDINGS: 36 participants were enrolled into the study, of whom 24 were women and 12 men. 12 women and six men received each dose. 204 adverse events were reported among the 36 participants, of which 200 (98%) were grade 1-2. The most common adverse event was injection site reaction. All grade 3 and 4 adverse events were deemed not related to rilpivirine. Geometric mean (90% CI) concentrations in plasma of rilpivirine at day 28 post dose were 53 ng/mL (38-67) in women and 43 ng/mL (23-63) in men for the 1200 mg dose and 28 ng/mL (19-37) in women and 17 ng/mL (9-24) in men for the 600 mg dose. The tissue-to-plasma ratio for rilpivirine in rectal tissue was about two-fold higher than in vaginal and cervical tissue (1.10-1.53 vs 0.61-0.72 and 0.50-0.71, respectively). Exposure to long-acting rilpivirine suppressed viral replication significantly in rectal tissue (p<0.0001), and this suppression persisted for up to 4 months. By contrast, no viral suppression was seen in cervical or vaginal tissue. INTERPRETATION: Ongoing research will characterise longer term safety and acceptability of multiple injections and help ascertain whether long-acting rilpivirine should advance to assessment of efficacy in preventing HIV-1 infection. FUNDING: Bill & Melinda Gates Foundation. PMID- 27658866 TI - Next-generation sequencing and HIV drug resistance surveillance. PMID- 27658868 TI - First-line integrase inhibitors for HIV-prices versus benefits. PMID- 27658867 TI - Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey. AB - BACKGROUND: WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods. METHODS: Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9.4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression. FINDINGS: Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15.5%, 95% CI 11.4-20.5) had pretreatment resistance to any antiretroviral drug and 28 (10.6%, 7.2-15.0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score >=15) was noted in 13 (4 . 9%) of participants to efavirenz and in 23 (8.7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14.4%, 95% CI 10.4-19.2) had pretreatment resistance to any antiretroviral drug and 26 (9.8%, 6.5-14.1) had pretreatment resistance to NNRTIs. After median follow-up of 8 months (IQR 6.5-9.4, range 5 11) after ART initiation, 97 (72%) of 135 NNRTI initiators achieved viral suppression (<50 copies per mL) compared with ten (40%) of 25 individuals who started with protease inhibitor-based regimens (p=0.0045). After multivariate regression considering pretreatment resistance and initial ART regimen as composite variables, people starting NNRTIs with pretreatment drug resistance achieved significantly lower viral suppression (odds ratio 0.24, 95% CI 0.07 0.74; p=0.014) than patients without NNRTI resistance. INTERPRETATION: High levels of pretreatment drug resistance were noted in Mexico, and NNRTI pretreatment drug resistance significantly reduced the effectiveness of first line ART regimens based on these drugs. Baseline HIV-drug resistance testing for initial ART follow-up and decision making should be considered. FUNDING: The Mexican Government and Consejo Nacional de Ciencia y Tecnologia. PMID- 27658869 TI - Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. AB - BACKGROUND: New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART regimens for HIV in ART-naive patients. METHODS: For this systematic review and network meta-analysis, we searched for randomised clinical trials published up to July 5, 2015, comparing recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. We extracted data on trial and patient characteristics, and the following primary outcomes: viral suppression, mortality, AIDS defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events. We synthesised data using network meta-analyses in a Bayesian framework and included older treatments, such as indinavir, to serve as connecting nodes. We defined network nodes in terms of specific antivirals rather than specific ART regimens. We categorised backbone regimens and adjusted for them through group-specific meta-regression. We used the GRADE framework to interpret the strength of inference. FINDINGS: We identified 5865 citations through database searches and other sources, of which, 126 articles related to 71 unique trials were included in the network analysis, including 34 032 patients randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the odds ratio (OR) for viral suppression was 1.87 (95% credible interval [CrI] 1.34-2.64) with dolutegravir and 1.40 (1.02-1.96) with raltegravir; with respect to viral suppression, low dose efavirenz was similar to all other treatments. Both low-dose efavirenz and integrase strand transfer inhibitors tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz. The most protective effect relative to efavirenz in network meta-analyses was that of dolutegravir (OR 0.26, 95% CrI 0.14-0.47), followed by low-dose efavirenz (0.39, 0.16-0.92). Owing to insufficient data, we could make no conclusions about serious adverse events. Low event rates also limited the quality of evidence with regard to mortality and AIDS defining illnesses. INTERPRETATION: The efficacy and safety of ART has substantially improved with the introduction of newer drug classes of antiretrovirals that are now available to patients and HIV care providers. Their improved tolerance could be part of a larger solution to improve retention, which is a challenge, particularly in low-income and middle-income country settings. FUNDING: The World Health Organization. PMID- 27658871 TI - The benefits and risks of PrEP and kidney function. PMID- 27658870 TI - Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study. AB - BACKGROUND: As pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine for the prevention of HIV infection is rolled out internationally, strategies to maintain effectiveness and to minimise adverse effects merit consideration. In this study, we aimed to assess reductions in renal function and predictors of renal toxicity in a large open-label study of PrEP. METHODS: As part of the iPrEx open-label extension (OLE) study, men who have sex with men or transgender women aged 18-70 years who were HIV negative and had participated in three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the USA were enrolled into an open-label PrEP study. There were no restrictions on current renal function for enrolment into iPrEx OLE, in which participants were given combination tablets of tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) and advised to take one tablet per day. At follow-up sessions every 12 weeks, participants' creatinine clearance on PrEP was estimated and in a subset of participants, hair samples were collected to measure tenofovir and emtricitabine concentrations (a measure of adherence and exposure) via liquid-chromatography-tandem-mass-spectrometry. Reductions in creatinine clearance from baseline were calculated and predictors of decline were identified by use of multivariate models. iPrEx is registered with ClinicalTrials.com, number NCT00458393. FINDINGS: Baseline characteristics were similar between all participants in iPrEx-OLE (1224 participants with 7475 person visits) and those participating in the hair substudy (220 participants with 1114 person-visits). During a median of 72 weeks, the mean decline in creatinine clearance was -2.9% (95% CI -2.4 to -3.4; ptrend<0.0001), but declines were greater for those who started PrEP at older ages: participants aged 40-50 years at baseline had declines of -4.2% (95% CI -2.8 to -5.5) and participants older than 50 years at baseline had declines of -4.9% (-3.1 to -6.8). In multivariate models, age and baseline creatinine clearance less than 90 mL/min predicted declines in renal function. We identified a monotonic association between percentage decrease in creatinine clearance and the number of doses of tenofovir disoproxil fumarate and emtricitabine taken per week, as estimated by hair concentrations of tenofovir and emtricitabine (ptrend=0.008). INTERPRETATION: Our data suggest that the frequency of safety monitoring for PrEP might need to be different between age groups and that pharmacological measures can monitor for toxic effects as well as adherence. FUNDING: National Institutes of Health. PMID- 27658872 TI - Accelerating initiation of antiretroviral therapy. PMID- 27658874 TI - Heightened epidemic in men who have sex with men in Brazil. PMID- 27658873 TI - Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial. AB - BACKGROUND: In Africa, up to 30% of HIV-infected patients who are clinically eligible for antiretroviral therapy (ART) do not start timely treatment. We assessed the effects of an intervention targeting prevalent health systems barriers to ART initiation on timing and completeness of treatment initiation. METHODS: In this stepped-wedge, non-blinded, cluster-randomised controlled trial, 20 clinics in southwestern Uganda were randomly assigned in groups of five clinics every 6 months to the intervention by a computerised random number generator. This procedure continued until all clinics had crossed over from control (standard of care) to the intervention, which consisted of opinion-leader led training and coaching of front-line health workers, a point-of-care CD4 cell count testing platform, a revised counselling approach without mandatory multiple pre-initiation sessions, and feedback to the facilities on their ART initiation rates and how they compared with other facilities. Treatment-naive, HIV-infected adults (aged >=18 years) who were clinically eligible for ART during the study period were included in the study population. The primary outcome was ART initiation 14 days after first clinical eligibility for ART. This study is registered with ClinicalTrials.gov, number NCT01810289. FINDINGS: Between April 11, 2013, and Feb 2, 2015, 12 024 eligible patients visited one of the 20 participating clinics. Median CD4 count was 310 cells per MUL (IQR 179-424). 3753 of 4747 patients (weighted proportion 80%) in the intervention group had started ART by 2 weeks after eligibility compared with 2585 of 7066 patients (38%) in the control group (risk difference 41.9%, 95% CI 40.1-43.8). Vital status was ascertained in a random sample of 208 patients in the intervention group and 199 patients in the control group. Four deaths (2%) occurred in the intervention group and five (3%) occurred in the control group. INTERPRETATION: A multicomponent intervention targeting health-care worker behaviour increased the probability of ART initiation 14 days after eligibility. This intervention consists of widely accessible components and has been tested in a real-world setting, and is therefore well positioned for use at scale. FUNDING: National Institute of Allergy and Infectious Diseases (NIAID) and the President's Emergency Fund for AIDS Relief (PEPFAR). PMID- 27658876 TI - Paediatric HIV testing beyond the context of prevention of mother-to-child transmission: a systematic review and meta-analysis. AB - BACKGROUND: Many HIV-positive children in low-income and middle-income countries remain undiagnosed. Although HIV testing in children at health facilities is recommended by WHO, it is not well implemented. This systematic review and meta analysis examines the case-finding benefit of HIV screening in children aged 0-5 years in low-income and middle-income countries. METHODS: We did this systematic review and meta-analysis in accordance with an a-priori protocol. We searched PubMed, MEDLINE, WHO Global Index Medicus, Web of Science, Medecins Sans Frontieres, Cochrane, Embase, CABS Abstracts, and LILACS databases for articles published between Jan 1, 2004, and April 30, 2016, that reported the quantitative prevalence of HIV detected through screening in four key contexts (paediatric inpatient settings, paediatric outpatient settings, nutrition centres, and expanded programme on immunisation centres) in paediatric populations in low income and middle-income countries. Articles were identified and data were extracted in duplicate. The primary outcome was HIV prevalence, for which we used a DerSimonian-Laird random-effects meta-analysis to pool prevalence data and 95% CIs. We did stratified analyses according to geographical context and testing strategy. This study is registered with PROSPERO, number CRD42014014372. FINDINGS: Our search found 2996 studies, of which 26 met the inclusion criteria. Paediatric HIV prevalence across all settings was 15.6% (95% CI 11.8-19.5). HIV prevalence by setting was highest in paediatric inpatient settings (21.1%, 95% CI 14.9-27.3), followed by nutrition centres (13.1%, 95% CI 3.4-22.7), expanded programme on immunisation centres (3.3%, 95% CI 0-6.9), and paediatric outpatient settings (2.7%, 95% CI 0.3-5.2). Universal testing and testing triggered by symptoms had similar diagnostic yield in the inpatient setting (21.3%, 95% CI 11.6-31.0 in triggered testing vs 20.9%, 95% CI 13.5-28.3 in universal testing). INTERPRETATION: HIV testing in paediatric populations in low-income and middle income countries outside the context of prevention of mother-to-child transmission programmes provides an important opportunity to identify HIV positive children. For countries wishing to prioritise interventions, the highest diagnostic yields were obtained from inpatient wards and nutrition centres. Universal testing might be the preferred approach since it did not have a substantially lower diagnostic yield than triggered testing FUNDING: None. PMID- 27658875 TI - Mortality in HIV-infected women, heterosexual men, and men who have sex with men in Rio de Janeiro, Brazil: an observational cohort study. AB - BACKGROUND: Mortality in HIV-infected individuals might differ by sex and mode of HIV acquisition. We aimed to study mortality in HIV-infected women, heterosexual men, and men who have sex with men (MSM) in a cohort from Rio de Janeiro, Brazil. METHODS: In this observational cohort study, we included HIV-infected women, heterosexual men, and MSM (aged >=18 years) from the Instituto Nacional de Infectologia Evandro Chagas database who were enrolled between Jan 1, 2000, and Oct 30, 2011, and who had at least 60 days of follow-up. Causes of deaths, defined with the Coding of Death in HIV protocol, were documented. Cox proportional hazards models accounting for competing risks were used to explore risk factors for AIDS-related and non-AIDS-related deaths. FINDINGS: We had 10 142 person-years of follow-up from 2224 individuals: 817 (37%) women, 554 (25%) heterosexual men, and 853 (38%) MSM. Of 103 deaths occurred, 64 were AIDS related, 31 were non-AIDS related, and eight were of unknown causes. In unadjusted analyses, compared with women, the hazard of AIDS-related deaths was higher for heterosexual men (hazard ratio [HR] 3.52, 95% CI 1.30-9.08; p=0.009) and for MSM (2.30, 0.89-5.94; p=0.084). After adjustment for age, CD4 cell counts, last HIV viral load, antiretroviral therapy use, and AIDS-defining infection, AIDS-defining malignant disease, and hospital admission during follow up, the excess risk of AIDS-related death decreased for heterosexual men (adjusted HR 1.99, 0.75-5.25; p=0.163) but was unchanged for MSM (2.24, 0.82 6.11; p=0.114). Non-AIDS-related mortality did not differ by group. INTERPRETATION: Compared with women, increased risk of AIDS-related death in heterosexual men was partly mitigated by risk factors for AIDS mortality, whereas the excess risk in MSM was unchanged. Further study of reasons for disparity in AIDS-related mortality by mode of transmission is needed. FUNDING: US National Institutes of Health, Brazilian National Council of Technological and Scientific Development (CNPq), and Research Funding Agency of the State of Rio de Janeiro (FAPERJ). PMID- 27658877 TI - Expanding coverage of paediatric HIV testing. PMID- 27658878 TI - Curbing HIV incidence in people who inject drugs. PMID- 27658879 TI - HIV incidence among people who inject drugs (PWIDs) in Ukraine: results from a clustered randomised trial. AB - BACKGROUND: HIV prevalence among people who inject drugs (PWID) in Ukraine is among the highest in the world. In this study, we aimed to assess whether a social network intervention was superior to HIV testing and counselling in affecting HIV incidence among PWID. Although this was not the primary aim of the study, it is associated with reducing drug and sex risk behaviours, which were primary aims. METHODS: In this clustered randomised trial, PWID who were 16 years of age or older, had used self-reported drug injection in the past 30 days, were willing to be interviewed for about 1 hour and tested for HIV, were not too impaired to comprehend and provide informed consent, and, for this paper, who tested HIV negative at baseline were recruited from the streets by project outreach workers in three cities in southern and eastern Ukraine: Odessa, Donetsk, and Nikolayev. Index or peer leaders, along with two of their network members, were randomly assigned (1:1) by the study statistician to the testing and counselling block (control group) or the testing and counselling plus a social network intervention block (intervention group). No stratification or minimisation was done. Participants in the network intervention received five sessions to train their network members in risk reduction. Those participants assigned to the control group received no further intervention after counselling. The main outcome of this study was HIV seroconversion in the intent-to-treat population as estimated with Cox regression and incorporating a gamma frailty term to account for clustering. This trial is registered with ClinicalTrial.gov, number NCT01159704. FINDINGS: Between July 12, 2010, and Nov 23, 2012, 2304 PWIDs were recruited, 1200 of whom were HIV negative and are included in the present study. 589 index or peer leaders were randomly assigned to the control group and 611 were assigned to the intervention group. Of the 1200 HIV-negative participants, 1085 (90%) were retained at 12 months. In 553.0 person-years in the intervention group, 102 participants had seroconversion (incidence density 18.45 per 100 person-years; 95% CI 14.87-22.03); in 497.1 person-years in the control group 158 participants seroconverted (31.78 per 100 person-years; 26.83-36.74). This corresponded to a reduced hazard in the intervention group (hazard ratio 0.53, 95% CI 0.38-0.76, p=0.0003). No study-related adverse events were reported. INTERPRETATION: These data provide strong support for integrating peer education into comprehensive HIV prevention programmes for PWID and suggest the value in developing and testing peer-led interventions to improve access and adherence to pre-exposure prophylaxis and antiretroviral therapy. FUNDING: The National Institute on Drug Abuse. PMID- 27658880 TI - The doctor's dilemma and vaccine therapy for HIV. PMID- 27658882 TI - Peripheral and bone marrow CD34+ cell levels on chronic myeloproliferative disease. AB - PURPOSE: The aim of the present study was to examine the relationship between peripheral CD34+ and bone marrow CD34+ levels and the clinicopathologic characteristics and laboratory parameters of myeloproliferative disease (MPD) patients. PATIENTS AND METHODS: A total of 103 MPD patients were enrolled in this study. We examined the relationship between bone marrow CD34+ and peripheral CD34+ levels and the patients' clinicopathologic and laboratory parameters. RESULTS: There were no significant correlations between the peripheral CD34+ levels and the JAK-2 V617F mutation, thrombosis, white blood cells (WBC), lactate dehydrogenase (LDH), transferrin saturation (TS), ferritin, or bone marrow cellularity. In addition, there were no significant correlations between bone marrow CD34+ levels and the JAK-2 V617F mutation, thrombosis, WBC, LDH, TS, ferritin, or bone marrow cellularity (P > 0.05). We did not identify any significant relationship between peripheral CD34+ and bone marrow CD34+ levels (P > 0.05). However, there were significant correlations between peripheral CD34+ levels and bone marrow fibrosis (P < 0.001), between bone marrow CD34+ levels and constitutional symptoms (P < 0.05), and between bone marrow CD34+ levels and bone marrow fibrosis (P < 0.001). CONCLUSION: We did not find any significant relationship between the clinicopathologic and laboratory characteristics and peripheral and bone marrow CD34+ cells from bone marrow fibrosis patients. There was also no significant relationship between bone marrow CD34+ cells and peripheral CD34+ cells. Some peripheral CD34+ cells may originate from the spleen rather than the bone marrow, which may given us different result of some parameters. PMID- 27658883 TI - Commentary: expectations for global health program prioritization from a selection of international students studying at a European university. AB - BACKGROUND: Some university curricula struggle to present evidence-based promotion of global health principles and global health diplomacy within an undergraduate setting. The de facto global health paradigm has experienced significant stress and pressure from epidemics, war and violence, climate change and resource challenges. These stressors may lead to increased morbidity and mortality, in turn requiring medical professionals to play a larger role in global health action across borders. METHODS: In the academic year 2014-2015, an English-speaking international medical school promoted a global health forum with pre-course readings and a pre-attendance quiz. All students from the university were invited to attend and the event was not mandatory. RESULTS: The one-day event culminated in expert speakers, discussions and a post-event questionnaire to gauge students' reactions and expectations as future physicians regarding the most pressing global health topics. Emphasis was also placed on what future doctors foresee as pressing issues in forthcoming global health policy and programming. This paper is a brief commentary of the Global Health Forum in Prague 2014, and presents novel results from a post-event student questionnaire, with conclusions provided by students on innovative global health policy. PMID- 27658881 TI - Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial. AB - BACKGROUND: Depression is highly prevalent in people with HIV and has consistently been associated with poor antiretroviral therapy (ART) adherence. Integrating cognitive behavioural therapy (CBT) for depression with adherence counselling using the Life-Steps approach (CBT-AD) has an emerging evidence base. The aim of this study was to test the efficacy of CBT-AD. METHODS: In this three arm randomised controlled trial in HIV-positive adults with depression, we compared CBT-AD with information and supportive psychotherapy plus adherence counselling using the Life-Steps approach (ISP-AD), and with enhanced treatment as usual (ETAU) including Life-Steps adherence counselling only. Participants were recruited from three sites in New England, USA (two hospital settings and one community health centre). Patients were randomly assigned (2:2:1) to receive CBT-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), ISP-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), or ETAU (one Life-Steps session and five assessment visits roughly every 2 weeks), randomisation was done with allocation software, in pairs, and stratified by three variables: study site, whether or not participants had been prescribed antidepressant medication, and whether or not participants had a history of injection drug use. The primary outcome was ART adherence at the end of treatment (4 month assessment) assessed via electronic pill caps (Medication Event Monitoring System [MEMS]) with correction for pocketed doses, analysed by intention to treat. FINDINGS: Patients were recruited from Feb 26, 2009, to June 21, 2012. Patients who were assigned to CBT-AD (94 randomly assigned, 83 completed assessment) had greater improvements in adherence (estimated difference 1.00 percentage point per visit, 95% CI 0.34 to 1.66, p=0.003) and depression (Center for Epidemiological Studies depression [CESD] score estimated difference -0.41, -0.66 to -0.16, p=0.001; Montgomery-Asberg depression rating scale [MADRS] score -4.69, -8.09 to -1.28, p=0.007; clinical global impression [CGI] score -0.66, -1.11 to -0.21, p=0.005) than did patients who had ETAU (49 assigned, 46 completed assessment) after treatment (4 months). No significant differences in adherence were noted between CBT-AD and ISP-AD (97 assigned, 87 completed assessment). No study-related adverse events were reported. INTERPRETATION: Integrating evidenced-based treatment for depression with evidenced-based adherence counselling is helpful for individuals living with HIV/AIDS and depression. Future efforts should examine how to best disseminate effective psychosocial depression treatments such as CBT-AD to people living with HIV/AIDS and examine the cost-effectiveness of such approaches. FUNDING: National Institute of Mental Health, National Institute of Allergy and Infectious Diseases. PMID- 27658884 TI - An analysis on the roles of angiogenesis-related factors including serum vitamin D, soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt1), and vascular endothelial growth factor (VEGF) in the diagnosis and severity of late onset preeclampsia. AB - AIM: The aim of this study was to evaluate the roles of proangiogenic factors including serum vitamin D and vascular endothelial growth factor (VEGF) and anti angiogenic factors including soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in the diagnosis and severity of late-onset preeclampsia. MATERIALS AND METHODS: The study was conducted at Yuzuncu Yil University Research and Education Hospital Department of Gynecology and Obstetrics. The study included a patient group of 40 women with late-onset preeclampsia who were pregnant at >=32 weeks of gestation according to the last menstrual period (LMP) or ultrasonographic fetal biometric measurement and a control group of 40 healthy pregnant women who presented to our clinic for routine pregnancy examination and were at the same age and gestational period with those in the patient group. The two groups were compared in terms of maternal age, gravida, parity, week of gestation, systolic/diastolic blood pressure, total protein in spot urine sample, 24-h urine protein, white blood cell (WBC), hemoglobin (Hgb), platelet count, urea, creatinine, liver function tests (AST, ALT, LDH), vitamin D3, 25(OH) vitamin D3, 1,25(OH) vitamin D3, sEng, sFlt1, and VEGF levels, mode of delivery, the infant APGAR score at 1 and 5 min after delivery, and infant weight at delivery. RESULTS: The groups were similar in terms of age, gravida, parity, week of gestation, serum vitamin D3, 25(OH) vitamin D3, 1,25(OH)2 vitamin D3 and VEGF levels, and infant weight at delivery (p > 0.05). Systolic/diastolic blood pressure, total protein in spot urine sample, 24-h urine protein, WBC, Hgb, serum urea, creatine, AST, ALT, and LDH were significantly higher in the preeclamptic group compared to the healthy group (p < 0.05). However, thrombocyte level and the APGAR score at 1 and 5 min after delivery were significantly lower in the preeclamptic group compared to the healthy group (p < 0.05). No significant correlation was found between serum sEng, sFlt1, VEGF, vitamin D3, 25(OH) vitamin D3, and 1,25(OH)2 vitamin D3 levels. The sEng level was higher in the women with severe preeclampsia compared to the women with mild preeclampsia (p < 0.05) and no significant difference was observed in serum sFlt1, VEGF, vitamin D3, 25(OH) vitamin D3, and 1,25(OH)2 vitamin D3 levels between the subgroups of preeclampsia (p > 0.05). CONCLUSION: Both sEng and sFlt1 levels are remarkably high in patients with late-onset preeclampsia; however, only sEng may be a useful tool in the determination of the severity of preeclampsia. PMID- 27658886 TI - How can machine-learning methods assist in virtual screening for hyperuricemia? A healthcare machine-learning approach. AB - OBJECT: Our purpose was to develop a new machine-learning approach (a virtual health check-up) toward identification of those at high risk of hyperuricemia. Applying the system to general health check-ups is expected to reduce medical costs compared with administering an additional test. METHODS: Data were collected during annual health check-ups performed in Japan between 2011 and 2013 (inclusive). We prepared training and test datasets from the health check-up data to build prediction models; these were composed of 43,524 and 17,789 persons, respectively. Gradient-boosting decision tree (GBDT), random forest (RF), and logistic regression (LR) approaches were trained using the training dataset and were then used to predict hyperuricemia in the test dataset. Undersampling was applied to build the prediction models to deal with the imbalanced class dataset. RESULTS: The results showed that the RF and GBDT approaches afforded the best performances in terms of sensitivity and specificity, respectively. The area under the curve (AUC) values of the models, which reflected the total discriminative ability of the classification, were 0.796 [95% confidence interval (CI): 0.766-0.825] for the GBDT, 0.784 [95% CI: 0.752-0.815] for the RF, and 0.785 [95% CI: 0.752-0.819] for the LR approaches. No significant differences were observed between pairs of each approach. Small changes occurred in the AUCs after applying undersampling to build the models. CONCLUSIONS: We developed a virtual health check-up that predicted the development of hyperuricemia using machine-learning methods. The GBDT, RF, and LR methods had similar predictive capability. Undersampling did not remarkably improve predictive power. PMID- 27658885 TI - Development and validation of an electronic medical record-based alert score for detection of inpatient deterioration outside the ICU. AB - BACKGROUND: Patients in general medical-surgical wards who experience unplanned transfer to the intensive care unit (ICU) show evidence of physiologic derangement 6-24h prior to their deterioration. With increasing availability of electronic medical records (EMRs), automated early warning scores (EWSs) are becoming feasible. OBJECTIVE: To describe the development and performance of an automated EWS based on EMR data. MATERIALS AND METHODS: We used a discrete-time logistic regression model to obtain an hourly risk score to predict unplanned transfer to the ICU within the next 12h. The model was based on hospitalization episodes from all adult patients (18years) admitted to 21 Kaiser Permanente Northern California (KPNC) hospitals from 1/1/2010 to 12/31/2013. Eligible patients met these entry criteria: initial hospitalization occurred at a KPNC hospital; the hospitalization was not for childbirth; and the EMR had been operational at the hospital for at least 3months. We evaluated the performance of this risk score, called Advanced Alert Monitor (AAM) and compared it against two other EWSs (eCART and NEWS) in terms of their sensitivity, specificity, negative predictive value, positive predictive value, and area under the receiver operator characteristic curve (c statistic). RESULTS: A total of 649,418 hospitalization episodes involving 374,838 patients met inclusion criteria, with 19,153 of the episodes experiencing at least one outcome. The analysis data set had 48,723,248 hourly observations. Predictors included physiologic data (laboratory tests and vital signs); neurological status; severity of illness and longitudinal comorbidity indices; care directives; and health services indicators (e.g. elapsed length of stay). AAM showed better performance compared to NEWS and eCART in all the metrics and prediction intervals. The AAM AUC was 0.82 compared to 0.79 and 0.76 for eCART and NEWS, respectively. Using a threshold that generated 1 alert per day in a unit with a patient census of 35, the sensitivity of AAM was 49% (95% CI: 47.6-50.3%) compared to the sensitivities of eCART and NEWS scores of 44% (42.3-45.1) and 40% (38.2-40.9), respectively. For all three scores, about half of alerts occurred within 12h of the event, and almost two thirds within 24h of the event. CONCLUSION: The AAM score is an example of a score that takes advantage of multiple data streams now available in modern EMRs. It highlights the ability to harness complex algorithms to maximize signal extraction. The main challenge in the future is to develop detection approaches for patients in whom data are sparser because their baseline risk is lower. PMID- 27658887 TI - Heritability of serum dehydroepiandrosterone sulphate levels and pubertal development in 6~18-year-old girls: a twin study. AB - BACKGROUND: Dehydroepiandrosterone sulphate (DHEAS), the most plentiful circulating adrenal hormone, may be considered as a marker of the onset of adrenarche and is involved in pubertal development and metabolic disorders. AIM: The objective of this study is to determine the genetic and environmental influences on the variation of basal DHEAS levels and pubertal development in pubertal girls. SUBJECTS AND METHODS: Three hundred and sixty twin girls aged 6 18-years were enrolled, consisting of 132 monozygotic pairs and 48 dizygotic pairs. Anthropometric and sexual characteristics were examined. Serum DHEAS was measured by RIA. Estimates of genetic and environmental components of variance were based on the theory of normal maximum likelihood in Mx package. RESULTS: Serum DHEAS concentrations of PH-II and PH-III were significantly higher than Tanner stage PH-I (p < .05) and maintained higher levels in PH-IV ~ V. Heritability of serum DHEAS estimated by model-fitting on data from 180-pairs of twins is 0.61 (0.52-0.70), the rest of the variance in DHEAS levels could be explained by unique environmental influences and age. The heritabilities of DHEAS in two pubertal sub-groups (PH-I and PH-II-V) are 0.82 (0.71-0.90) and 0.63 (0.52 0.74), respectively. The heritability index of menarche, breast development and pube development are 0.71, 0.35 and 0.45, respectively. CONCLUSIONS: Serum DHEAS concentrations of pubertal girls are mainly influenced by genetic factors, especially during the period of adrenarche. The results stress the importance of research into the genetic regulation of the endocrine regulators involved in adrenarche and related metabolic disorders in girls. PMID- 27658888 TI - Derivatives of the pyrazolo[1,5-a]pyrimidine acetamide DPA-713 as translocator protein (TSPO) ligands and pro-apoptotic agents in human glioblastoma. AB - The 18kDa translocator protein (TSPO) is a target for novel glioblastoma therapies due to its upregulation in this cancer and relatively low levels of expression in the healthy cortex. The pyrazolo[1,5-a]pyrimidine acetamides, exemplified by DPA-713 and DPA-714, are a class of high affinity TSPO ligands with selectivity over the central benzodiazepine receptor. In this study we have explored the potential anti-glioblastoma activity of a library of DPA-713 and DPA 714 analogues, and investigated the effect of amending the alkyl ether chain on TSPO affinity and functional potential. All ligands demonstrated nanomolar affinity for TSPO, but showed diverse functional activity, for example DPA-713 and DPA-714 did not affect the proliferation or viability of human T98G glioblastoma cells, while the hexyl ether and benzyl ether derivatives decreased proliferation of T98G cells without affecting proliferation in human fetal glial SVGp12 cells. These ligands also induced apoptosis and dissipated T98G mitochondrial membrane potential. This suggests that the nature of the alkyl ether chain of pyrazolo[1,5-a]pyrimidine acetamides has little influence on TSPO affinity but is important for functional activity of this class of TSPO ligands. PMID- 27658889 TI - Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways. AB - Grape seed procyanidin extract (GSE) has been reported to exert antineoplastic properties via the inhibition of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) eicosanoid pathways. In addition, ample data link carcinogenesis to inflammatory events involving other major eicosanoid metabolic pathways, including prostacyclin (PGI2) and 15-hydroxyeicosatetraenoic acid (15-HETE). We therefore evaluated the effects of GSE on prostacyclin synthase (PTGIS)/PGI2 and 15 lipoxigenase-2 (15-LOX-2)/15-HETE productions by human lung premalignant and malignant cells and correlated the findings with antiproliferative or proapoptotic effects of GSE. The effects of GSE on PGI2 and 15-HETE productions by human bronchoalveolar lavage (BAL) cells ex vivo were also determined. We further evaluated the bioactivity of oral administration of leucoselect phytosome (a standardized GSE) in the lungs of subjects participating in a lung cancer chemoprevention trial, by comparing the antiproliferative effects of coculturing matched pre- versus posttreatment BAL fluids with lung premalignant and malignant cells. GSE significantly increased PGI2 (as measured by 6-keto PGF1alpha) and 15 HETE productions by these cells. Transfections of PTGIS or 15-LOX-2-specific siRNA partially abrogated the antiproliferative or proapoptotic effects of GSE in lung premalignant and malignant cells, respectively. GSE also increased PTGIS and inhibition of caspase-3, and transfection of 15-LOX-2 siRNA abrogated the GSE induced apoptosis in A549 cells. In addition, culture supernatants from ex vivo GSE-treated baseline BAL cells, as well as BAL fluids from subjects treated with leucoselect phytosome, significantly decreased proliferations of lung premalignant and malignant cells. Our findings support the continued investigation of GSE as an anti-neoplastic and chemopreventive agent against lung cancer. Cancer Prev Res; 9(12); 925-32. (c)2016 AACR. PMID- 27658890 TI - A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia. AB - Previous preclinical studies and a phase I clinical trial suggested that myo inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with >=1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906-14. (c)2016 AACR. PMID- 27658892 TI - Transcatheter aortic valve replacement in unicuspid aortic valve stenosis. AB - Unicuspid aortic valve (UAV) offers unique challenges to transcatheter aortic valve replacement (TAVR), due to asymmetric expansion and apposition of the prosthesis during implantation. Although TAVR in bicuspid is now a well described experience, TAVR in unicuspid valve has not yet been described. A challenging case is described with TAVR in UAV using a Edwards Sapiens prosthesis via transapical approach. (c) 2016 Wiley Periodicals, Inc. PMID- 27658891 TI - MicroRNA Signatures of Colonic Polyps on Screening and Histology. AB - Colorectal cancer and adenoma adjacent to cancer exhibit distinct microRNA (miRNA) alterations in an apparent mucosa-to-adenocarcinoma sequence. The pattern of microRNAs in screen-detected polyps in relation to histologic features and cancer risk has not been investigated. miRNA expression analysis was performed on normal mucosa (NM), hyperplastic polyps (HP), tubular adenomas (TA), tubulovillous adenomas or high-grade dysplasia (TVHG), and serrated polyps [sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA)] in biopsy specimens from 109 patients undergoing screening/surveillance colonoscopy. Generalized linear models were used to identify differentially expressed miRNAs by histologic type and logistic regression to identify miRNA predictors of histopathology. False discovery rate (FDR) was used to control for multiple comparisons. We identified 99 miRNAs differing in at least one of five histopathologic groups (FDR <=0.05). In a comparison of HPNM versus TVHG, the top most upregulated and downregulated miRNAs in HPNM included miR-145, -143, -107, 194, and -26a (upregulated), and miR-663, -1268, -320b, -1275, and -320b (downregulated; FDR P < 0.05). miR-145 and -619 showed high accuracy to discriminate low- from high-risk polyps without serrated histology (TVHG vs. HPNM + TA; CI, 95.6%), whereas miR-124, -143, and -30a showed high accuracy of separating high-risk polyps (TVHG + TSA) from low-risk polyps (HPNM + TA + SSA/P; CI, 96.0%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs, and miR-335, -222, and -214 discriminated between non-serrated and serrated histology. Our data support the presence of colorectal cancer-associated miRNA alterations in screen-detected adenomas that may be useful for risk stratification for surveillance interval planning. Cancer Prev Res; 9(12); 942-9. (c)2016 AACR. PMID- 27658893 TI - The six obesity indices, which one is more compatible with metabolic syndrome? A population based study. AB - OBJECTIVES: The present study was conducted to determine the best discriminators in the diagnosis of the metabolic syndrome (MetS) among six obesity indexes. Furthermore the optimal cutoff points for all obesity indexes were determined. METHODS: The baseline data of 5910 subjects of Haraz cohort study which was conducted in northern Iran were analyzed. Receiver operating characteristic (ROC) analyses were separately performed to determine discriminatory power of six obesity indexes, including, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), abdominal volume index (AVI) and conicity index (CI) for diagnosis of at least two other components of MetS. Youden index was used to determine the optimal cutoff points. RESULTS: While the optimal cutoff points in men were 26.0kg/m2 for BMI, 90cm for WC, 0.90 for WHR, 0.53 for WHtR, 16.6 (cm2) for AVI and 1.24(m32/kg12) for CI, the optimal values in women were 29.0kg/m2 for BMI, 91cm for WC, 0.86 for WHR, 0.58 for WHtR, 17.0(cm2) for AVI and 1.23 (m32/kg12) for CI. The prevalence of overweight or obesity was 46.1% to 54.1% in women and 49.5% to 53.6% in men based on various obesity indexes. The area under the ROC curves (AUCs) varied from 0.671(0.651 0.690) for CI to 0.718(0.700-0.736) for WC in men and from 0.668 (0.646-0.690) for BMI to 0.755(0.735-0.774) for WHR and CI in women. CONCLUSION: Except for CI in men and BMI in women, other obesity indexes were good discriminator in the diagnosis of the MetS. PMID- 27658894 TI - A unified Hyperglycemia and Diabetic ketoacidosis (DKA) insulin infusion protocol based on an Excel algorithm and implemented via Electronic Medical Record (EMR) in Intensive Care Units. AB - BACKGROUND: To assess the efficacy of a unified hyperglycemia and diabetic ketoacidosis (DKA) insulin infusion protocol (IIP), based on an Excel algorithm and implemented as an electronic order set, in achieving glycemic targets and minimizing hypoglycemia. METHODS: An IIP was instituted in medical and surgical intensive care units for post-cardiac surgery (PCS) and other stress hyperglycemia (SH), diabetes hyperglycemia (DH), and DKA. The IIP initiated therapeutic insulin rates at elevated blood glucose (BG), and decreased insulin when target range was achieved. A convenience sample (n=62) was studied; 20 PCS, 15 with DH, 9 with SH, 8 with diabetes on vasopressors, 7 with diabetes on glucocorticoids and 3 with DKA were assessed. RESULTS: The protocol maintained BG at 144+/-24.7mg/dL for PCS and 167+/-36mg/dL for patients with diabetes mellitus. It maintained acceptable target range (ATR) (100mg/dL-180mg/dL) 89% of the time for PCS and 67% of the time for patients with diabetes mellitus. There were no measurements of BG<70mg/dL. The protocol lowered the BG at a similar rate and time period in those with diabetes, DKA and those with or without vasopressors or glucocorticoids. To determine long-term efficacy, a retrospective review of Point of Care (POC) RALS (Remote Automated Data System) BG data 2 years post implementation demonstrated fewer episodes of hypoglycemia<70mg/dL and hyperglycemia>240mg/dL and more BG values within ATR. CONCLUSIONS: This IIP maintained ATR without hypoglycemia for patients in the ICU setting without requiring complex nursing calculations. PMID- 27658895 TI - Reevaluation of anti-obesity action of mazindol and elucidation of its effect on the reward system. AB - In this study, we evaluated the preventive effect of mazindol on the development of obesity and sought to elucidate the drug's effects on the reward system. In mice, body weight gain and hyperphagia induced by high-fat diet (HFD) were decreased by 38.6% and 13.9%, respectively, by subcutaneous infusion of mazindol (1.5mg/kg/day) for 28days. A single intraperitoneal administration of mazindol (1.5mg/kg) significantly reduced lipid preference, as assessed using the two bottle preference paradigm (vehicle, 89.98+/-1.66%; mazindol, 75.65+/-5.47%; p<0.05). In addition, the conditioned place preference (CPP) test demonstrated that mazindol (1.5mg/kg) significantly decreased CPP score for HFD as compared with vehicle (vehicle, 330.44+/-58.61s; mazindol, 144.72+/-43.02s; p<0.05). Moreover, at the dose required for these effects, mazindol did not elicit abuse potential or induce psychostimulant-like behavior. These results confirm that mazindol prevents diet-induced obesity without addictive behavior and demonstrate that its action is mediated at least in part via the reward system, advancing our understanding of mazindol in clinical practice. PMID- 27658896 TI - Author's reply. PMID- 27658897 TI - Systematic identification and management of barriers to vascular surgery patient discharge time of day. AB - OBJECTIVE: Length of stay fails to completely capture the clinical and economic effects of patient progression through the phases of inpatient care, such as admission, room placement, procedures, and discharge. Delayed hospital throughput has been linked to increased time spent in the emergency department and postanesthesia care unit, delayed time to treatment, increased in-hospital mortality, decreased patient satisfaction, and lost hospital revenue. We identified barriers to vascular surgery inpatient care progression and instituted defined measures to positively impact standardized metrics. METHODS: The study was divided into three periods: preintervention, "wash-in," and postintervention. During the preintervention phase, barriers to patient flow were quantified by an interdisciplinary team. Suboptimal provider communication emerged as the key barrier. An enhanced communication intervention consisting of face-to-face and mobile application-based education on key patient flow metrics, explicit discussion of individual patient barriers to progression at rounds and interdisciplinary huddles, and communication of projected discharge and potential barriers via e-mail was developed with input from all stakeholders. Following a 4 week wash-in implementation phase, data collection was repeated. RESULTS: The pre and postintervention patient cohorts accounted for 244.3 and 238.1 inpatient days, respectively. Both groups had similar baseline demographic, clinical characteristics, and procedures performed during hospitalization. The postintervention group was discharged 78 minutes earlier (14:00:32 vs 15:18:37; P = .03) with a trend toward increased discharge by noon (94% vs 88%; P = .09). Readmission rates did not differ (P = .44). CONCLUSIONS: Implementation of a focused, interdisciplinary, frontline provider-driven, enhanced communication program can be feasibly incorporated into existing specialty surgical workflow. The program resulted in improved timeliness of discharge and projected cost savings, without increasing readmission rates. PMID- 27658898 TI - Places where children are active: A longitudinal examination of children's physical activity. AB - Using two-year longitudinal data, we examined locations where children spent time and were active, whether location patterns were stable, and relationships between spending time in their home neighborhood and moderate to vigorous physical activity (MVPA). At two time points (2007-2009 and 2009-2011), children living in the metropolitans areas of either San Diego, CA or Seattle, WA wore an accelerometer, and parents recorded their child's locations for seven days. Across two years, global average proportion of time spent in each location was stable, but total time and proportion of time in each location spent in MVPA decreased significantly across all locations. Children spent the largest proportion of time in MVPA in their home neighborhood at both time points, although they spent little time in their home neighborhood. PMID- 27658899 TI - Shared use agreements between municipalities and public schools in the United States, 2014. AB - Shared use agreements allow public use of school facilities during non-school hours. Such agreements can cover outdoor facilities alone or may be more comprehensive by also including indoor facilities. Our aim was to: 1) estimate the prevalence of shared use agreements and facility types covered among U.S. municipalities and 2) identify differences in prevalence by municipality characteristics. The 2014 National Survey of Community-based Policy and Environmental Supports for Healthy Eating and Active Living is a representative survey of US municipalities (n=2029). Data were analyzed using survey weights to create national estimates. Logistic and multinomial regression models determined odds ratios adjusting for municipality characteristics. Among 1930 municipalities with a school, 41.6% had a shared use agreement as reported by a local official, 45.6% did not, and 12.8% did not know. Significant differences in prevalence existed by population size, rural/urban status, poverty prevalence, median education level, and census region; however, after adjustment for other municipality characteristics significant differences remained only by population size, median education level, and census region. Among municipalities with a shared use agreement, 59.6% covered both outdoor and indoor facilities, 5.5% covered indoor facilities only, and 34.9% covered outdoor facilities only. Opportunities exist to expand the use of shared use agreements particularly in municipalities with small populations, lower education levels, and in the South, and to promote more comprehensive shared use agreements that include both indoor and outdoor facilities. PMID- 27658900 TI - Changes in Female Drosophila Sleep following Mating Are Mediated by SPSN-SAG Neurons. AB - Female Drosophila melanogaster, like many other organisms, exhibit different behavioral repertoires after mating with a male. These postmating responses (PMRs) include increased egg production and laying, increased rejection behavior (avoiding further male advances), decreased longevity, altered gustation and decreased sleep. Sex Peptide (SP), a protein transferred from the male during copulation, is largely responsible for many of these behavioral responses, and acts through a specific circuit to induce rejection behavior and alter dietary preference. However, less is known about the mechanisms and neurons that influence sleep in mated females. In this study, we investigated postmating changes in female sleep across strains and ages and on different media, and report that these changes are robust and relatively consistent under a variety of conditions. We find that female sleep is reduced by male-derived SP acting through the canonical sex peptide receptor (SPR) within the same neurons responsible for altering other PMRs. This circuit includes the SPSN-SAG neurons, whose silencing by DREADD induces postmating behaviors including sleep. Our data are consistent with the idea that mating status is communicated to the central brain through a common circuit that diverges in higher brain centers to modify a collection of postmating sensorimotor processes. PMID- 27658902 TI - A Tale of Two Types of Perspective Taking: Sex Differences in Spatial Ability. AB - Sex differences in favor of males have been documented in measures of spatial perspective taking. In this research, we examined whether social factors (i.e., stereotype threat and the inclusion of human figures in tasks) account for these differences. In Experiment 1, we evaluated performance when perspective-taking tests were framed as measuring either spatial or social (empathetic) perspective taking abilities. In the spatial condition, tasks were framed as measures of spatial ability on which males have an advantage. In the social condition, modified tasks contained human figures and were framed as measures of empathy on which females have an advantage. Results showed a sex difference in favor of males in the spatial condition but not the social condition. Experiments 2 and 3 indicated that both stereotype threat and including human figures contributed to these effects. Results suggest that females may underperform on spatial tests in part because of negative performance expectations and the character of the spatial tests rather than because of actual lack of abilities. PMID- 27658903 TI - From Caregivers to Peers: Puberty Shapes Human Face Perception. AB - Puberty prepares mammals to sexually reproduce during adolescence. It is also hypothesized to invoke a social metamorphosis that prepares adolescents to take on adult social roles. We provide the first evidence to support this hypothesis in humans and show that pubertal development retunes the face-processing system from a caregiver bias to a peer bias. Prior to puberty, children exhibit enhanced recognition for adult female faces. With puberty, superior recognition emerges for peer faces that match one's pubertal status. As puberty progresses, so does the peer recognition bias. Adolescents become better at recognizing faces with a pubertal status similar to their own. These findings reconceptualize the adolescent "dip" in face recognition by showing that it is a recalibration of the face-processing system away from caregivers toward peers. Thus, in addition to preparing the physical body for sexual reproduction, puberty shapes the perceptual system for processing the social world in new ways. PMID- 27658901 TI - TYROBP genetic variants in early-onset Alzheimer's disease. AB - We aimed to identify new candidate genes potentially involved in early-onset Alzheimer's disease (EOAD). Exome sequencing was conducted on 45 EOAD patients with either a family history of Alzheimer's disease (AD, <65 years) or an extremely early age at the onset (<=55 years) followed by multiple variant filtering according to different modes of inheritance. We identified 29 candidate genes potentially involved in EOAD, of which the gene TYROBP, previously implicated in AD, was selected for genetic and functional follow-up. Using 3 patient cohorts, we observed rare coding TYROBP variants in 9 out of 1110 EOAD patients, whereas no such variants were detected in 1826 controls (p = 0.0001), suggesting that at least some rare TYROBP variants might contribute to EOAD risk. Overexpression of the p.D50_L51ins14 TYROBP mutant led to a profound reduction of TREM2 expression, a well-established risk factor for AD. This is the first study supporting a role for genetic variation in TYROBP in EOAD, with in vitro support for a functional effect of the p.D50_L51ins14 TYROBP mutation on TREM2 expression. PMID- 27658904 TI - Outcome and surgical strategy in critical sites in cases of psuedomyxoma peritonei. AB - BACKGROUND: For a long time peritoneal neoplasms were considered beyond surgical intervention and beyond cure, till the concept of cytoreductive surgery (CRS) and adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced. However this surgical intervention is technically demanding and associated with considerable postoperative morbidity. OBJECTIVE: To describe the surgical strategy in resection of critical sites loaded by heavy tumor deposits and to evaluate short and long term results of CRS and HIPEC, in a cohort of Egyptian patients with pseudomyxoma peritonei (PMP) from appendiceal origin. PATIENTS AND METHODS: 21 patients with PMP, age ranged from 40 to 63years, 12 males and 9 females. All were recruited from the department of surgery at the National Cancer Institute (NCI), Cairo University over the period from February 2011 to February 2016. They were subjected to CRS and HIPEC with mitomycin-C. RESULTS: The median peritoneal carcinoma index (PCI) was 22 (range: 10-39). Optimal cytoreduction (CCR-0/1) was achieved in 19 patients (90.4%) of whom 17 patients (80.9%) had a complete cytoreduction (CCR-0). The median follow up period was 51.5months (range: 0.07-82.3months). The cumulative overall survival was 85.7% while the cumulative disease free survival was 76.9%. CONCLUSION: To the best of our knowledge, this is the first study reporting five years postoperative outcome of CRS and HIPEC in Egyptian patients with PMP from appendiceal origin. Our results support that although technically demanding this treatment modality is safe and associated with favorable outcome. PMID- 27658905 TI - Efficacy of intra-articular corticosteroid injection in erosive hand osteoarthritis: infrared thermal imaging. PMID- 27658906 TI - Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett's esophagus using high-quality histological correlation. AB - BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) provides a circumferential scan that enables visualization of the subsurface layers of the esophageal wall at 7 MUm resolution. The aims of this study were to identify VLE features of Barrett's esophagus (BE) neoplasia and to develop a VLE prediction score. METHODS: A database of VLE images from endoscopic resection specimens, precisely correlated with histology, from patients with BE with and without neoplasia was used. Features potentially predictive for early BE neoplasia were identified by unblinded evaluation of 25 VLE-histology images. In a learning phase, 20 VLE images with or without BE neoplasia were scored by 2 VLE experts, blinded to histology. A prediction score was created by using multivariable logistic regression analyses and validated by scoring 40 VLE images (50% neoplastic) by using area under receiver operating characteristic (ROC) curve (AUC) analysis. RESULTS: Three VLE features independently predictive for BE neoplasia were identified: (1) lack of layering; (2) higher surface than subsurface signal; (3) presence of irregular, dilated glands/ducts. A VLE neoplasia prediction score was developed with the following: (1) 6 points; (2) 6 or 8 points for equal or higher surface signal; and (3) 5 points. The ROC curve of this prediction score showed an AUC of 0.81 (95% confidence interval, 0.71 0.90). A cut-off value of >=8 was associated with sensitivity and specificity of 83% and 71%, respectively. CONCLUSIONS: When high-quality ex vivo VLE-histology correlation was used, the VLE features of layering, surface signal, and irregular glands/ducts were independently and significantly associated with BE neoplasia. A VLE prediction score for BE neoplasia was developed and validated, with promising accuracy. (Clinical trial registration number: NCT01862666.). PMID- 27658907 TI - Comparing diagnostic yield of a novel pan-enteric video capsule endoscope with ileocolonoscopy in patients with active Crohn's disease: a feasibility study. AB - BACKGROUND AND AIMS: Crohn's disease (CD) is typically diagnosed with ileocolonoscopy (IC); however, when inflammation is localized solely in the small bowel, visualization of the entire small-bowel mucosa can be challenging. The aim of this study was to compare the diagnostic yield of a pan-enteric video capsule endoscope (small-bowel colon [SBC] capsule) versus IC in patients with active CD. METHODS: This was a prospective, multicenter study. Patients with known active CD and proven bowel luminal patency underwent a standardized colon cleansing protocol followed by ingestion of the capsule. After passage of the capsule, IC was performed and recorded. Lesions indicative of active CD were assessed. RESULTS: One hundred fourteen subjects were screened; 66 subjects completed both endoscopic procedures. The per-subject diagnostic yield rate for active CD lesions was 83.3% for SBC and 69.7% for IC (yield difference, 13.6%; 95% confidence interval [CI], 2.6%-24.7%); 65% of subjects had active CD lesions identified by both modalities. Of the 12 subjects who were positive for active CD by SBC only, 5 subjects were found to have active CD lesions in the terminal ileum. Three subjects were positive for active CD by IC only. Three hundred fifty five classifying bowel segments were analyzed; the per-segment diagnostic yield rate was 40.6% for SBC and 32.7% for IC (yield difference 7.9%; 95% CI, 3.3% 12.4%). CONCLUSION: This preliminary study shows that the diagnostic yields for SBC might be higher than IC; however, the magnitude of difference between the two is difficult to estimate. Further study is needed to confirm these findings. PMID- 27658908 TI - Colonoscopy. PMID- 27658910 TI - Mathematical model of tumor volume dynamics in mice treated with electrochemotherapy. AB - The effectiveness of electrochemotherapy, a local treatment using electric pulses to increase the uptake of chemotherapeutic drug, includes several antitumor mechanisms. In addition to the cytotoxic action of chemotherapeutic drug, treatment outcome also depends on antitumor immune response. In order to assess the contribution of different antitumor mechanisms to the observed treatment outcome, we designed a model of tumor volume dynamics, which is able to quantify early and late treatment effects. Model integrates characteristics of both main posttreatment processes, namely removal of lethally damaged cells from tumor volume and tumor-immune interaction. Fitting to individual responses gives the insight into the dynamics of tumor cell elimination. Two more or less clearly separable peaks can be observed from these dynamics. Model was used to quantify responses obtained after chemotherapy and electrochemotherapy with bleomycin and cisplatin in immunocompetent and immunodeficient mice. As expected, electrochemotherapy resulted in higher number of lethally damaged cells as well as in stronger immune response compared to chemotherapy alone. Additionally, bleomycin-treated tumors proved to be more immunogenic than cisplatin-treated tumors in the given range of doses. PMID- 27658911 TI - Effect of Phyllostachys parvifolia leaf extract on ionizing radiation-induced genetic damage: A preliminary in vitro cytogenetic study. AB - The ionizing radiation is a known carcinogen as well as cancer therapeutic agent however, the side effect on normal tissue is a limiting factor and inadequate doses necessitates search for an ideal radioprotective agent. Bamboo species are rich source of antioxidants hence have therapeutic value in many free radical mediated diseases. This is the first report regarding in vitro protective effect of bamboo leaf extract against radiation induced genetic damage in human peripheral blood lymphocytes by cytokinesis blocked micronuclei (CBMN) assay. Fresh whole blood was exposed to 5Gy of cobalt-6o gamma radiation with or without 30 min pre-treatment with 3 MUl and 5 MUl of hydro alcoholic leaf extract of Phyllostachys parvifolia. In addition to whole extract the effect of potential active compound orientin was also assessed. The frequency of radiation induced micronuclei decreased significantly in a dose dependent manner following treatment with whole extract as well as orientin. The extent of reduction in micronuclei frequency was higher with whole bamboo leaf extract as compared to orientin alone. PMID- 27658912 TI - Clinical trials in Ayurveda: Analysis of clinical trial registry of India. AB - Ayurveda is one of the complementary and alternative systems of medicine requiring generation of high quality evidence for rational practice. Evidence can be generated from study designs and the present study is an attempt to critically assess the registered studies in the field of Ayurveda from clinical trial registry of India. We found low number of trials conducted with more focus required on the quality of these studies to contribute to high quality evidence. PMID- 27658913 TI - Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis. AB - BACKGROUND: Chronic pain patients increasingly seek treatment through mindfulness meditation. PURPOSE: This study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults. METHOD: We conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use. RESULTS: Thirty-eight RCTs met inclusion criteria; seven reported on safety. We found low quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life. CONCLUSIONS: While mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain. PMID- 27658914 TI - Efficacy and Mediation of a Theory-Based Physical Activity Intervention for African American Men Who Have Sex with Men: A Randomized Controlled Trial. AB - BACKGROUND: Few trials have tested physical-activity interventions among sexual minorities, including African American men who have sex with men (MSM). PURPOSE: We examined the efficacy and mediation of the Being Responsible for Ourselves (BRO) physical-activity intervention among African American MSM. METHOD: African American MSM were randomized to the physical-activity intervention consisting of three 90-min one-on-one sessions or an attention-matched control intervention and completed pre-intervention, immediately post-intervention, and 6- and 12-month post-intervention audio computer-based surveys. RESULTS: Of the 595 participants, 503 completed the 12-month follow-up. Generalized estimating equation models revealed that the intervention increased self-reported physical activity compared with the control intervention, adjusted for pre-intervention physical activity. Mediation analyses suggested that the intervention increased reasoned action approach variables, subjective norm and self-efficacy, increasing intention immediately post-intervention, which increased physical activity during the follow-up period. CONCLUSIONS: Interventions targeting reasoned action approach variables may contribute to efforts to increase African American MSM's physical activity. CLINICAL TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov Identifier NCT02561286 . PMID- 27658916 TI - Erratum to: Moving Transgender Care Forward within Public Health Organizations: Inclusion of Facial Feminizing Surgery in the Swedish National Treatment Recommendations. PMID- 27658918 TI - DSM-5 and the Paraphilic Disorders: Conceptual Issues. PMID- 27658915 TI - Personality and Risk of Frailty: the English Longitudinal Study of Ageing. AB - BACKGROUND: There is evidence that the personality traits conscientiousness, extraversion and neuroticism are associated with health behaviours and with risk of various health outcomes. We hypothesised that people who are lower in conscientiousness or extraversion or higher in neuroticism may be at greater risk of frailty in later life. METHODS: We used general linear models to examine the prospective relation between personality, assessed using the Midlife Development Inventory, and change in frailty, modelled by a frailty index, in 5314 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. RESULTS: Men and women with higher levels of neuroticism or lower levels of extraversion or conscientiousness had an increased frailty index score at follow up. After adjustment for potential confounding or mediating variables, including frailty index score at baseline, the frailty index score at follow-up-which potentially ranges from 0 to 1-was higher by 0.035 (95 % confidence interval 0.018, 0.052) for a standard deviation increase in neuroticism and lower by 0.061 (0.031, 0.091) or 0.045 (0.020, 0.071) for a standard deviation increase in extraversion or conscientiousness, respectively. There was some evidence that the association between extraversion and frailty may be due to reverse causation whereby poorer health affected responses to items in the personality inventory. CONCLUSIONS: Higher levels of neuroticism or lower levels of conscientiousness or extraversion may be risk factors for the onset or progression of frailty. Future studies need to replicate these observations in other populations and explore the mechanisms underlying these associations. PMID- 27658917 TI - Gender Incongruence of Childhood Diagnosis and Its Impact on Brazilian Healthcare Access. PMID- 27658919 TI - Circularly Polarized Luminescence from Axially Chiral BODIPY DYEmers: An Experimental and Computational Study. AB - With our new home-built circularly polarized luminescence (CPL) instrument, we measured fluorescence and CPL spectra of the enantiomeric pairs of two quasi isomeric BODIPY DYEmers 1 and 2, endowed with axial chirality. The electronic circular dichroism (ECD) and CPL spectra of these atropisomeric dimers are dominated by the exciton coupling between the main pi-pi* transitions (550-560 nm) of the two BODIPY rings. Compound 1 has strong ECD and CPL spectra (glum =4*10-3 ) well reproduced by TD-DFT and SCS-CC2 (spin-component scaled second order approximate coupled-cluster) calculations using DFT-optimized ground- and excited-state structures. Compound 2 has weaker ECD and CPL spectra (glum =4*10-4 ), partly due to the mutual cancellation of electric-electric and electric magnetic exciton couplings, and partly to its conformational freedom. This compound is computationally very challenging. Starting from the optimized excited state geometries, we predicted the wrong sign for the CPL band of 2 using TD-DFT with the most recommended hybrid and range-separated functionals, whereas SCS-CC2 or a DFT functional with full exact exchange provided the correct sign. PMID- 27658920 TI - DNA damage inhibits lateral root formation by up-regulating cytokinin biosynthesis genes in Arabidopsis thaliana. AB - Lateral roots (LRs) are an important organ for water and nutrient uptake from soil. Thus, control of LR formation is crucial in the adaptation of plant growth to environmental conditions. However, the underlying mechanism controlling LR formation in response to external factors has remained largely unknown. Here, we found that LR formation was inhibited by DNA damage. Treatment with zeocin, which causes DNA double-strand breaks, up-regulated several DNA repair genes in the LR primordium (LRP) through the signaling pathway mediated by the transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1). Cell division was severely inhibited in the LRP of zeocin-treated sog1-1 mutant, which in turn inhibited LR formation. This result suggests that SOG1-mediated maintenance of genome integrity is crucial for proper cell division during LRP development. Furthermore, zeocin induced several cytokinin biosynthesis genes in a SOG1 dependent manner, thereby activating cytokinin signaling in the LRP. LR formation was less inhibited by zeocin in mutants defective in cytokinin biosynthesis or signaling, suggesting that elevated cytokinin signaling is crucial for the inhibition of LR formation in response to DNA damage. We conclude that SOG1 regulates DNA repair and cytokinin signaling separately and plays a key role in controlling LR formation under genotoxic stress. PMID- 27658921 TI - Initiation and Intensification Strategies in Type 2 Diabetes Management: A Comparison of Basal Plus and Premix Regimens. AB - : The progressive nature of type 2 diabetes (T2D) often results in the need for initiation and subsequent intensification of insulin treatment to achieve glycemic control. The aim of this review is to examine published clinical evidence that has directly compared two recommended treatment approaches in patients with T2D: (1) a 'basal plus' regimen, whereby 1-2 injections of prandial insulin are added to basal insulin; or (2) the use of once- or twice-daily premix insulin analogs, which contain both basal and prandial insulin in a single injection. Broadly, the available evidence suggests that both basal plus and premix regimens are comparable in terms of efficacy and safety when used for insulin initiation in insulin-naive patients and intensification in patients who have failed on basal insulin; instances of greater glycemic control are observed with premix insulin; however, these are often accompanied by increases in hypoglycemia and/or weight relative to basal plus treatment, and results should be interpreted within the context of total insulin doses used. Relatively low numbers of patients achieved glycemic control when both regimens were used for insulin intensification following failure of basal insulin, suggesting that a full basal-bolus regimen and/or the use of different treatments is clinically indicated in certain patients. In summary, the current review argues that both basal plus and premix insulin regimens are relatively efficacious and safe options for patients with T2D during both insulin initiation in insulin-naive patients and intensification in patients who have failed on basal insulin. This emphasizes the important role of patient-centered factors in clinical decision making. FUNDING: Novo Nordisk. PMID- 27658922 TI - Usefulness of the Atrial Emptying Fraction to Predict Maintenance of Sinus Rhythm After Direct Current Cardioversion for Atrial Fibrillation. AB - Atrial volumes indexed to body surface area (AVI) are robust predictors of nonvalvular atrial fibrillation (AF) recurrence after direct current cardioversion (DCCV). The incremental value of atrial emptying fraction (EmF) compared with atrial volumes as a predictor for recurrent AF after DCCV has not been evaluated. We sought to compare the predictive ability of baseline left atrial (LA) EmF, right atrial (RA) EmF, LAVI, and RAVI for post-DCCV AF recurrence at 6 months. The first 95 patients enrolled in the AF Clinic Registry with adequate echocardiogram imaging constituted the study cohort. Each patient underwent echocardiogram within 6 months before cardioversion. Maximal LAVI and RAVI, LA EmF, and RA EmF were performed offline using 4-chamber single-plane Simpson's method, averaged over 5 cycles. The mean age of the study cohort was 64 +/- 12 years, and 67% were men. Only 28 patients (29%) who underwent DCCV remained in sinus rhythm at 6 months of follow-up. The remaining, 67 (71%) had reverted to AF or underwent ablation during the 6 months of follow-up. The overall performance for prediction of AF recurrence was greatest for RA EmF, area under the receiver operator characteristic curve (AUC): RA EmF 0.92, LA EmF 0.89, RAVI 0.76, and LAVI 0.63. RA and LA EmF AUCs were significantly higher than for LAVI or RAVI (max p = 0.02). In conclusion, although RAVI and LAVI are strong predictors of AF recurrence after DCCV, RA and LA EmF outperformed in this cohort. PMID- 27658923 TI - Facial fracture repair and diabetes mellitus: An examination of postoperative complications. AB - OBJECTIVES/HYPOTHESIS: Our objectives included using a nationally representative resource to evaluate charges, demographics, and complication rates among diabetics undergoing surgical repair of facial fractures. METHODS: We evaluated the Nationwide Inpatient Sample, a database encompassing nearly 8 million hospitalizations, for patients with a diagnosis of a facial fracture who underwent surgical intervention during their hospitalization. Patients were organized by whether they had a diagnosis of diabetes mellitus (DM). RESULTS: Of 45,509 inpatients included, diabetics had greater costs, longer length of stays, and were significantly more likely to have a host of baseline comorbidities. On multivariate logistic regression corrected for age, race, gender, and preexisting cardiac disease, DM patients had significantly greater odds for cardiac complications (3.3; P < 0.001) and hepatic failure (15.0; P = 0.007). There were no significant differences associated with DM in the rates of enophthalmos, epiphora, and diplopia among patients with orbital fractures. Diabetics did have a significantly greater risk of postoperative infection after mandible repair. CONCLUSION: In addition to a significant association with greater length of stay and increased hospital charges, DM patients undergoing surgical repair of facial fractures had a significantly greater risk of postoperative complications, including cardiac complications. Diabetics undergoing mandible repair had a greater risk of postoperative infection, even upon controlling for demographic factors, suggesting the need for further study evaluating the role of postoperative antibiotic prophylaxis in this patient population. These findings reveal the potential value of developing and using standardized postoperative care algorithms aimed at minimizing complications in this susceptible population. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:809-814, 2017. PMID- 27658924 TI - Toward an Understanding of Divergent Compound Eye Development in Drones and Workers of the Honeybee (Apis mellifera L.): A Correlative Analysis of Morphology and Gene Expression. AB - Eye development in insects is best understood in Drosophila melanogaster, but little is known for other holometabolous insects. Combining a morphological with a gene expression analysis, we investigated eye development in the honeybee, putting emphasis on the sex-specific differences in eye size. Optic lobe development starts from an optic lobe anlage in the larval brain, which sequentially gives rise to the lobula, medulla, and lamina. The lamina differentiates in the last larval instar, when it receives optic nerve projections from the developing retina. The expression analysis focused on seven genes important for Drosophila eye development: eyes absent, sine oculis, embryonic lethal abnormal vision, minibrain, small optic lobes, epidermal growth factor receptor, and roughest. All except small optic lobes were more highly expressed in third-instar drone larvae, but then, in the fourth and fifth instar, their expression was sex-specifically modulated, showing shifts in temporal dynamics. The clearest differences were seen for small optic lobes, which is highly expressed in the developing eye of workers, and minibrain and roughest, which showed a strong expression peak coinciding with retina differentiation. A microarray analysis for optic lobe/retina complexes revealed the differential expression of several metabolism-related genes, as well as of two micro-RNAs. While we could not see major morphological differences in the developing eye structures before the pupal stage, the expression differences observed for the seven candidate genes and in the transcriptional microarray profiles indicate that molecular signatures underlying sex-specific optic lobe and retina development become established throughout the larval stages. PMID- 27658926 TI - Endoscopic ultrasound-guided fine needle aspiration biopsy of pancreatic lesions. An 8-year analysis of single institution material focusing on efficacy and learning progress. AB - OBJECTIVE: To evaluate the efficacy and the learning curve of the endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) diagnostics of pancreatic lesions over 8 years (2007-2014). MATERIAL AND METHODS: EUS-FNAB using a Linear Echoendoscope Olympus was performed in 531 patients, mostly without rapid on-site evaluation (ROSE). Smears plus cytoblock sections were used routinely. Immunocytochemistry was utilised as indicated. RESULTS: The average, satisfactory sampling rate increased from the 61.2% in the first 3-year period to 72.9% in the last 3-year period (P = 0.008). The availability of the material for cytoblocks increased from 36.4% in the first period to 75.3% in the last period (P = 0.017). The efficacy of cytoblocks increased from 39.6% to 46.2% (P = 0.086). Comparing the first and last 3-year periods, the indication for immunocytochemistry did not rise substantially (5.2% and 8.5% respectively), but the predictive value of immunocytochemistry rose from 56.3% to 100.0% (P = 0.001). The most frequent diagnostic result was malignancy confirmation - both primary (41.2%) and metastatic (2.1%). In cases with representative samples and follow-up information, the specificity, sensitivity, positive predictive value and accuracy were high from the beginning. The negative predictive value decreased slightly in the last 3-year period. CONCLUSION: The pancreatic EUS-FNAB without ROSE represents a suboptimal arrangement conditioned with our staff/time/location reality. Nevertheless, within the last 3 years of our activity, nearly three-quarters of patients profit from the diagnostic contribution of this procedure. PMID- 27658925 TI - Long Term Home-Based Exercise is Effective to Reduce Blood Pressure in Low Income Brazilian Hypertensive Patients: A Controlled Trial. AB - INTRODUCTION: Home-based exercise programs may increase adherence to physical activity among groups with poor access to exercise facilities. However, their effectiveness to lower blood pressure of hypertensive patients remains undefined. AIMS: This controlled clinical trial investigated the influence of a home-based exercise program upon blood pressure, blood metabolic profile, and physical fitness in a Brazilian cohort of low income patients diagnosed with hypertension. METHODS: Twenty-nine patients (22 women, age: 53 +/- 11 years) underwent 16 months of home-based exercise, including 30 min of moderate intensity walking and stretching exercises. Fourteen patients (9 women, age: 48 +/- 5 years) composed a non-exercise control group. Primary outcomes were assessed each two months. RESULTS: Body mass (3.6 +/- 0.2 kg; P = 0.03) and sum of skinfolds (3.0 +/- 1.2 cm; P = 0.04) increased in controls vs. baseline. Mean compliance to home-based exercise was 83 +/- 7 %, which induced significant improvements from baseline vs. controls in body mass (-5.4 +/- 2.0 kg; P = 0.04), body fat (-4.7 +/- 0.3 %; P = 0.03), waist circumference (-6.1 +/- 1.2 cm; P = 0.03), sum of skinfolds (-14.8 +/- 3.7; P = 0.02); aerobic efficiency reflected by slopes of relationships between heart rate and workload (-0.05 +/- 0.01; P = 0.05), trunk flexibility (7.8 +/- 1.7 cm; P = 0.02), HDL (1.8 +/- 0.9 mg/dL; P = 0.04), triglycerides ( 12.3 +/- 1.0 mg/dL; P = 0.03), and glucose (-6.9 +/- 2.9 mg/dL; P = 0.05). Systolic and diastolic BP decreased until the sixth month of intervention vs. baseline and controls, remaining stable at lower levels thereafter (systolic blood pressure: -4.5 +/- 0.3 mmHg; P = 0.03; diastolic blood pressure: -2.5 +/- 0.6 mmHg; P = 0.05). CONCLUSIONS: Low income hypertensive patients complied with a long-term home-based exercise program, which was effective for improving their functional capacity, blood metabolic profile, and blood pressure. PMID- 27658927 TI - Altered functional brain connectivity in children and young people with opsoclonus-myoclonus syndrome. AB - AIM: Opsoclonus-myoclonus syndrome (OMS) is a rare, poorly understood condition that can result in long-term cognitive, behavioural, and motor sequelae. Several studies have investigated structural brain changes associated with this condition, but little is known about changes in function. This study aimed to investigate changes in brain functional connectivity in patients with OMS. METHOD: Seven patients with OMS and 10 age-matched comparison participants underwent 3T magnetic resonance imaging (MRI) to acquire resting-state functional MRI data (whole-brain echo-planar images; 2mm isotropic voxels; multiband factor *2) for a cross-sectional study. A seed-based analysis identified brain regions in which signal changes over time correlated with the cerebellum. Model-free analysis was used to determine brain networks showing altered connectivity. RESULTS: In patients with OMS, the motor cortex showed significantly reduced connectivity, and the occipito-parietal region significantly increased connectivity with the cerebellum relative to the comparison group. A model-free analysis also showed extensive connectivity within a visual network, including the cerebellum and basal ganglia, not present in the comparison group. No other networks showed any differences between groups. INTERPRETATION: Patients with OMS showed reduced connectivity between the cerebellum and motor cortex, but increased connectivity with occipito-parietal regions. This pattern of change supports widespread brain involvement in OMS. PMID- 27658928 TI - Investigation of the atrial conduction time measured by tissue Doppler imaging at the left atrial appendage and the actual electrical conduction time: consideration of left atrial remodeling in atrial fibrillation patients. AB - PURPOSE: The atrial conduction time measured by echocardiography using tissue Doppler imaging (TDI) has been reported as a predictive factor of left atrial (LA) remodeling. We investigated the P wave to LA appendage (LAA) conduction time defined by transthoracic echocardiography using TDI (P-LAA TDI), and directly compared the actual LA electrical conduction time determined by the electrophysiological data. Additionally, we confirmed the clinical utility of the P-LAA TDI by examining the relationship to the electroanatomical LA remodeling data. METHODS: Sixty-three AF patients (22 paroxysmal AF, 41 persistent AF) underwent ablation and electroanatomical LA mapping. The P-LAA TDI was measured after the ablation and was compared with the electrophysiological data during sinus rhythm, including the actual electrical conduction time. RESULTS: A strong linear correlation (r = 0.776, p < 0.001, y = 1.28x + 49) was observed between the P-LAA TDI (161 +/- 24 ms) and electrophysiological P-LAA time (87 +/- 15 ms). The P-LAA TDI was also strongly correlated with the LA volume (173 +/- 52 ml, r = 0.632, p < 0.001) and LA conduction velocity index (1.07 +/- 0.19 mm/ms, r = 0.735, p < 0.001), but less to the focal anterior-LVA region surface area (2.2 [0.4-5.0] cm2, r = 0.380, p = 0.002). Additionally, a stepwise multiple linear regression demonstrated that both the LA volume and LA conduction velocity index were strongly associated with the value of the P-LAA TDI (p < 0.001). CONCLUSIONS: The P-LAA TDI was useful for estimating the actual electrophysiological conduction time and represented both electrical and anatomical LA remodeling. PMID- 27658929 TI - Ultrabroadband Design for Linear Polarization Conversion and Asymmetric Transmission Crossing X- and K- Band. AB - In this work, a high-efficiency and broadband reflective converter using ultrathin planar metamaterial (MM) composed of single-layered SRR is firstly realized. Numerical and experimental results demonstrate that the cross polarization conversion reflectance above 0.84 is achieved from 8.6 to 18.6 GHz for linearly polarized (LP) incident waves under normal incidence. Subsequently, a multi-layered MM based on SRR enables a dramatic improvement of the recently demonstrated asymmetric transmission (AT) effect. Theoretical and measured results present that strong one-way transmission of two orthogonally polarized waves crossing C- and K- band has been observed. These two separated AT pass bands have a function of selective polarization filter, which can be switched on/off by changing the polarization state of incident waves. The physical mechanisms are elucidated by taking advantage of electric fields and current distributions. Considering the broad bandwidth and the dual band, we believe that these two structures will be beneficial for designing polarization-controlled and selective transmission converter. PMID- 27658930 TI - Isolation and Characterization of a Moderately Virulent Classical Swine Fever Virus Emerging in China. AB - Classical swine fever (CSF) is a devastating infectious disease of pigs caused by classical swine fever virus (CSFV). In China, CSF has been under control owing to extensive vaccination with the lapinized attenuated vaccine (C-strain) since 1950s, despite sporadic or endemic in many regions. However, recently, CSF outbreaks occurred in a large number of swine herds in China. Here, we isolated 15 CSFV strains from diverse C-strain-vaccinated pig farms in China and characterized the genetic variations and antigenicity of the new isolates. The new strains showed unique variations in the E2 protein and were clustered to the subgenotype 2.1d of CSFV recently emerging in China in the phylogenetic tree. Cross-neutralization test showed that the neutralizing titres of porcine anti-C strain sera against the new isolates were substantially lower than those against both the highly virulent Shimen strain and the subgenotype 2.1b strains that were isolated in China in 2006 and 2009, respectively. In addition, experimental animal infection showed that the HLJZZ2014 strain-infected pigs displayed lower mortality and less severe clinical signs and pathological changes compared with the Shimen strain-infected pigs. The HLJZZ2014 strain was defined to be moderately virulent based on a previously established assessment system for CSFV virulence evaluation, and the virus shedding and the viral load in various tissues of the CSFV HLJZZ2014 strain-infected pigs were significantly lower than those of the Shimen strain-infected pigs. Taken together, the subgenotype 2.1d isolate of CSFV is a moderately virulent strain with molecular variations and antigenic alterations. PMID- 27658931 TI - Caring for People with Diabetes at the End of Life. AB - End-of-life care planning is assuming global significance. While general end-of life care guidelines apply to diabetes, there are some diabetes-specific issues that need to be considered. These include the usual long trajectory to end-of life care that enables clinicians and people with diabetes to proactively discuss when to change the focus of care from preventing diabetes complications (tight control) to a palliative approach. Palliative care aims to promote comfort and quality of life and reduce the unnecessary burden of care on individuals and their families. The aim of this paper is to discuss common disease trajectories and their relationship to diabetes care, outline strategies for proactively discussing these issues and suggest indications that palliative care is warranted. PMID- 27658932 TI - Urinary Proteomics for Diagnosis and Monitoring of Diabetic Nephropathy. AB - The last decade has seen a surge in publications describing novel biomarkers for early detection of diabetic nephropathy (DN), but as yet none have outperformed albuminuria in well-designed prospective studies. This is partially attributable to our incomplete understanding of the many complex interrelated mechanisms underlying DN development, a heterogeneous process unlikely to be captured by a single biomarker. Proteomics offers the advantage of simultaneously analysing the entire protein content of a biological sample, and the technique has gained attention as a potential tool for a more accurate diagnosis of disease at an earlier stage as well as a means by which to unravel the pathogenesis of complex diseases such as DN using an untargeted approach. This review will discuss the potential of proteomics as both a clinical and research tool, evaluating exploratory work in animal models as well as diagnostic potential in human subjects. PMID- 27658934 TI - Executive Summary of the Joint Position Paper on Renal Denervation of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH). PMID- 27658933 TI - Imaging Atherosclerosis in Diabetes: Current State. AB - Cardiovascular events, including myocardial infarction and stroke, are the primary causes of mortality in both type 1 and type 2 diabetes. Affected patients frequently have asymptomatic coronary artery disease. Studies have shown heterogeneity in cardiovascular risk among patients with diabetes. Imaging can help categorize risk of future cardiovascular events by identifying those patients with atherosclerosis, rather than relying on risk prediction based on population-based studies. In this article, we will review the evidence regarding use of atherosclerosis imaging in patients with diabetes to predict risk of coronary heart disease and mortality. PMID- 27658935 TI - Risk factors for unplanned readmission following head and neck microvascular reconstruction: Results from the National Surgical Quality Improvement Program, 2011-2014. AB - INTRODUCTION: Unplanned readmissions are associated with decreased healthcare quality and increased costs. This nationwide study examines causes for unplanned readmission among head and neck cancer patients undergoing immediate microsurgical reconstruction. METHODS: Patients undergoing head and neck tumor resection with microsurgical reconstruction were identified in the 2011-2014 National Surgical Quality Improvement Program database. Clinical characteristics and complications were compared among patients who did and did not undergo unplanned readmission. Univariate and multivariate logistic regression analyses were performed. RESULTS: Database search revealed 1,063 patients, 94 (8.8%) of whom had unplanned readmissions. Readmitted patients had significantly higher ASA scores (14.9% vs.7.3% ASA class 4 patients; P = 0.03) and significantly higher rates of disseminated cancer (14.9% vs.7.1%; P = 0.01), laryngopharyngectomy (17.0% vs.6.9%; P = 0.0005), deep wound infection (22.3% vs.2.4%; P < 0.0001), wound dehiscence (19.1% vs.3.3%; P < 0.0001), and blood transfusion within 72 h of surgery (44.7% vs.32.6%; P = 0.02). Multivariate logistic regression revealed deep wound infection (OR = 8.65, P < 0.0001) and wound dehiscence (OR = 3.69, P = 0.0004) to be independent predictors of unplanned readmission. CONCLUSIONS: Deep wound infection and wound dehiscence were independent predictors of unplanned readmission among head and neck cancer patients undergoing immediate microsurgical reconstruction. Institutions should focus efforts on improving wound surveillance, outpatient strategies for wound care, and optimization of discharge planning for this complex patient population. PMID- 27658937 TI - What do we expect from a beauty? Facial attractiveness of the opposite sex gives rise to discrepancies in males' anticipation and demand. AB - Facial attractiveness plays a significant role in social interactions and the effect of beauty premium is frequently observed. Previous studies showed that observing attractive counterparts would alleviate one's sense of unfairness. However, the mechanism underlying this phenomenon remained to be clarified. In this study, male participants were engaged in a modified Dictator game as recipients and their electroencephalograms were recorded. They were convinced that anonymous females who vary in facial attractiveness played as dictators. An outcome anticipation stage was implemented before proposed offers were presented and we focused on the cognitive process of subjective anticipation. A less negative Stimulus-preceding negativity was observed in the attractive face condition, suggesting that subjects paid less anticipatory attention toward proposed offers, and subjective expectation toward fair ones was weakened when beauties played as dictators. Thus, this study provides additional neural evidences for the beauty premium effect and suggests a reasonable explanation for this commonly reported phenomenon. PMID- 27658936 TI - Mutation-adapted U1 snRNA corrects a splicing error of the dopa decarboxylase gene. AB - Aromatic l-amino acid decarboxylase (AADC) deficiency is an inborn error of monoamine neurotransmitter synthesis, which results in dopamine, serotonin, epinephrine and norepinephrine deficiencies. The DDC gene founder mutation IVS6 + 4A > T is highly prevalent in Chinese patients with AADC deficiency. In this study, we designed several U1 snRNA vectors to adapt U1 snRNA binding sequences of the mutated DDC gene. We found that only the modified U1 snRNA (IVS-AAA) that completely matched both the intronic and exonic U1 binding sequences of the mutated DDC gene could correct splicing errors of either the mutated human DDC minigene or the mouse artificial splicing construct in vitro. We further injected an adeno-associated viral (AAV) vector to express IVS-AAA in the brain of a knock in mouse model. This treatment was well tolerated and improved both the survival and brain dopamine and serotonin levels of mice with AADC deficiency. Therefore, mutation-adapted U1 snRNA gene therapy can be a promising method to treat genetic diseases caused by splicing errors, but the efficiency of such a treatment still needs improvements. PMID- 27658938 TI - Surface chemistry of black phosphorus under a controlled oxidative environment. AB - Black phosphorus (BP), the bulk counterpart of monolayer phosphorene, is a relatively stable phosphorus allotrope at room temperature. However, monolayer phosphorene and ultra-thin BP layers degrade in ambient atmosphere. In this paper, we report the investigation of BP oxidation and discuss the reaction mechanism based on the x-ray photoelectron spectroscopy (XPS) data. The kinetics of BP oxidation was examined under various well-controlled conditions, namely in 5% O2/Ar, 2.3% H2O/Ar, and 5% O2 and 2.3% H2O/Ar. At room temperature, the BP surface is demonstrated not to be oxidized at a high oxidation rate in 5% O2/Ar nor in 2.3% H2O/Ar, according to XPS, with the thickness of the oxidized phosphorus layer <5 A for 5 h. On the other hand, in the O2/H2O mixture, a 30 A thickness oxide layer was detected already after 2 h of the treatment. This result points to a synergetic effect of water and oxygen in the BP oxidation. The oxidation effect was also studied in applications to the electrical measurements of BP field-effect transistors (FETs) with or without passivation. The electrical performance of BP FETs with atomic layer deposition (ALD) dielectric passivation or h-BN passivation formed in a glove-box environment are also presented. PMID- 27658940 TI - Transcatheter Aortic Valve Implantation With or Without Preimplantation Balloon Aortic Valvuloplasty: A Systematic Review and Meta-Analysis. PMID- 27658941 TI - High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease. PMID- 27658944 TI - The impact of measurement of respiratory quotient by indirect calorimetry on the achievement of nitrogen balance in patients with severe traumatic brain injury. AB - BACKGROUND: This study evaluated the impact of IC on the optimization of nutritional support and the achievement of +NB in patients with TBI. MATERIALS AND METHODS: 27 patients (GCS <= 8), treated with a 5-day multimodality monitoring and goal-directed therapy protocol, received enteral nutrition on day 1 followed by IC on days 3 and 5 and assessment of NB on day 7. In the first cohort (n = 11), no adjustment in kcal was made. In the second cohort (n = 16), nutrition was targeted to an RQ of 0.83 by day 3. The first cohort was analyzed with respect to NB status; the second cohort was compared to patients with (-) and +NB of the first cohort. Data (mean +/- SD) were analyzed with unpaired t test, and Chi square and Fisher exact tests. RESULTS: 4/11(36 %) patients in the first cohort had +NB. The predicted mortality by TRISS, substrate utilization, and RQ was significantly lower compared to the second cohort. The mortality predicted by the CrasH model did not differ between the two cohorts. A RQ of 0.74 was associated with the preferential use of fat and protein and -NB, whereas a RQ of 0.84 favored utilization of carbohydrates and +NB. All patients whose kcal intake was adjusted based on the RQ on day 3 reached a +NB by day 7. CONCLUSION: An increase in kcal >=25 % in patients with a RQ < 0.83 on day 3 improves substrate utilization, decreases protein utilization and optimizes the achievement of +NB by day 7. PMID- 27658945 TI - Swine flu vaccine is unlikely to raise risk of overall birth defects, study finds. PMID- 27658939 TI - Bridging the gap between in vitro and in vivo RNA folding. AB - Deciphering the folding pathways and predicting the structures of complex three dimensional biomolecules is central to elucidating biological function. RNA is single-stranded, which gives it the freedom to fold into complex secondary and tertiary structures. These structures endow RNA with the ability to perform complex chemistries and functions ranging from enzymatic activity to gene regulation. Given that RNA is involved in many essential cellular processes, it is critical to understand how it folds and functions in vivo. Within the last few years, methods have been developed to probe RNA structures in vivo and genome wide. These studies reveal that RNA often adopts very different structures in vivo and in vitro, and provide profound insights into RNA biology. Nonetheless, both in vitro and in vivo approaches have limitations: studies in the complex and uncontrolled cellular environment make it difficult to obtain insight into RNA folding pathways and thermodynamics, and studies in vitro often lack direct cellular relevance, leaving a gap in our knowledge of RNA folding in vivo. This gap is being bridged by biophysical and mechanistic studies of RNA structure and function under conditions that mimic the cellular environment. To date, most artificial cytoplasms have used various polymers as molecular crowding agents and a series of small molecules as cosolutes. Studies under such in vivo-like conditions are yielding fresh insights, such as cooperative folding of functional RNAs and increased activity of ribozymes. These observations are accounted for in part by molecular crowding effects and interactions with other molecules. In this review, we report milestones in RNA folding in vitro and in vivo and discuss ongoing experimental and computational efforts to bridge the gap between these two conditions in order to understand how RNA folds in the cell. PMID- 27658943 TI - The Gustilo-Anderson classification system as predictor of nonunion and infection in open tibia fractures. AB - PURPOSE: We sought to conduct the largest retrospective study to date of open tibia fractures and describe the incidence of complications and evaluate the potential predictive risk factors for complications. METHODS: Patients with open tibia fractures treated with reamed intramedullary nail (IMN) across a 10-year period were evaluated. Patient charts were reviewed for demographics, type of open fracture (T), comorbidities, and postoperative complications. A multivariate model was conducted to determine the risk factors for each type of complication. RESULTS: Of the 486 patients with open tibia fractures, 13 % (n = 64) had infections, 12 % (n = 56) had nonunions, and 1 % (n = 7) had amputations. TIII fractures had much higher rates of each complication than TI and TII fractures. Fracture type was the only significant risk factor for both nonunion and infection. CONCLUSION: Our study found that the Gustilo grade of open tibia fracture is by far the greatest predictor of nonunion and infection. PMID- 27658942 TI - Algorithm for activation of coagulation support treatment in multiple injured patients--cohort study. AB - BACKGROUND: Early recognition and management of trauma related coagulopathy improves the outcome. Trauma facilities should implement an algorithm to identify the bleeding trauma patient with coagulopathy. OBJECTIVE: The scope of the paper is to identify the indicators of early coagulopathy and to optimize the indications for thromboelastometry and coagulation support. DESIGN: Cohort study based on data from trauma registry. SETTING: Data of 493 major trauma patients treated in GH Celje from 2006 to 2014 were included into The TraumaRegister DGU(r) (TR-DGU). PATIENTS: Patients were selected for inclusion into TR-DGU according to the following criteria: polytraumatized patients with Injury severity score (ISS) >= 18, patients with injuries to single region with AIS 5, patients with major injuries to a single region and abnormal vital signs. All patients that were dead on arrival to hospital, patients presented to hospital >24 h after the injury, and head injuries that occurred with a low energy mechanism in patients on anticoagulation drugs were excluded. MEASUREMENTS: Two groups were formed (with or without coagulopathy). Mortality, morbidity, length of mechanical ventilation, ICU and hospital stay were used as outcome and compared between the groups. A coagulopathy prediction model (CPM) was developed to identify the patients who were at high risk of coagulopathy. RESULTS: Coagulopathy was present in 51 % of patients. Severe injuries to the torso and limbs, infusion of >1000 ml of fluids in the prehospital settings, and hypotension were included into CPM. If all three criteria were present, the sensitivity of the model to predict coagulopathy was 93 %. By adding the blood gas analysis (BE <= -5), the specificity increased to 81.7 %. LIMITATIONS: Shortcomings of our analysis are mainly related to the quality of data in the registry that may not be comparable to a clinical trial where data are collected specifically to address a given issue. CONCLUSIONS: The Criteria for activation of coagulation support treatment remain centre dependent. In our settings the CPM is the tool to select patients for ROTEM(r) analysis. By adding data from blood gas analysis, treatment of coagulopathy is justifiable before complete test results are available. PMID- 27658946 TI - How consistent are lordosis, range of movement and lumbo-pelvic rhythm in people with and without back pain? AB - BACKGROUND: Comparing movements/postures in people with and without lower back pain (LBP) may assist identifying LBP-specific dysfunction and its relationship to pain or activity limitation. This study compared the consistency in lumbo pelvic posture and movement (range and pattern) in people with and without chronic LBP (>12 week's duration). METHODS: Wireless, wearable, inertial measurement units measured lumbar lordosis angle, range of movement (ROM) and lumbo-pelvic rhythm in adults (n = 63). Measurements were taken on three separate occasions: two tests on the same day with different raters and a third (intra rater) test one to two weeks later. Participants performed five repetitions of tested postures or movements. Test data were captured automatically. Minimal detectable change scores (MDC90) provided estimates of between-test consistency. RESULTS: There was no significant difference between participants with and without LBP for lordosis angle. There were significant differences for pelvic flexion ROM (LBP 60.8 degrees , NoLBP 54.8 degrees , F(1,63) = 4.31, p = 0.04), lumbar right lateral flexion ROM (LBP 22.2 degrees , NoLBP 24.6 degrees F(1,63) = 4.48, p = .04), trunk right lateral flexion ROM (LBP 28.4 degrees , NoLBP 31.7 degrees , F(1,63) = 5.9, p = .02) and lumbar contribution to lumbo-pelvic rhythm in the LBP group (LBP 45.8 %, F(1,63) = 4.20, NoLBP 51.3 % p = .044). MDC90 estimates for intra and inter-rater comparisons were 10 degrees -15 degrees for lumbar lordosis, and 5 degrees -15 degrees for most ROM. For lumbo-pelvic rhythm, we found 8-15 % variation in lumbar contribution to flexion and lateral flexion and 36-56 % variation in extension. Good to excellent agreement (reliability) was seen between raters (mean r = .88, ICC (2,2)). CONCLUSION: Comparisons of ROM between people with and without LBP showed few differences between groups, with reduced relative lumbar contribution to trunk flexion. There was no difference between groups for lordosis. Wide, within-group differences were seen for both groups for ROM and lordosis. Due to variability between test occasions, changes would need to exceed 10 degrees -15 degrees for lumbar lordosis, 5 degrees -15 degrees for ROM components, and 8-15 % of lumbar contribution to lumbo-pelvic rhythm, to have 90 % confidence that movements had actually changed. Lordosis, range of movement and lumbo-pelvic rhythm typically demonstrate variability between same-day and different-day tests. This variability needs to be considered when interpreting posture and movement changes. PMID- 27658947 TI - Acute Pulmonary Edema in an Eclamptic Pregnant Patient: A Rare Case of Takotsubo Syndrome. AB - BACKGROUND Acute pulmonary edema in a pregnant patient is associated with significant morbidity and mortality. Takotsubo syndrome, or stress-induced cardiomyopathy, is a rare cause of acute pulmonary edema in a pregnant patient, especially prior to delivery of the fetus. CASE REPORT We describe a case of a pregnant patient who presented with acute pulmonary edema and eclampsia and was found to have Takotsubo syndrome. To the best of our knowledge, eclampsia as a precipitating factor for Takotsubo syndrome has not been described in literature. CONCLUSIONS Clinicians taking care of pregnant patients should be aware of the potential link between eclampsia and Takotsubo cardiomyopathy. Prompt correction of the precipitating cause along with supportive management as described is the key to a successful outcome. PMID- 27658948 TI - Enhancing emergency care in low-income countries using mobile technology-based training tools. AB - In this paper, we discuss the role of mobile technology in developing training tools for health workers, with particular reference to low-income countries (LICs). The global and technological context is outlined, followed by a summary of approaches to using and evaluating mobile technology for learning in healthcare. Finally, recommendations are made for those developing and using such tools, based on current literature and the authors' involvement in the field. PMID- 27658949 TI - Magnetic Resonance Imaging Appearance and Mechanism of Action of Five Hemostatic Agents Used in Neurosurgery. AB - OBJECTIVE: To describe the magnetic resonance (MR) image appearance of 5 hemostatic agents placed in the brain, and to review their clinical application. STUDY DESIGN: Descriptive ex vivo and in vivo study. ANIMALS: Canine cadavers (n=4), client-owned dogs (n=4). METHODS: Heads from 4 canine cadavers were used, each with 5 hemostatic agents placed in specific locations in the brain. Hemostatic agents were used in their native form in 2 cadaveric brains, and in 2 others the materials were saturated with fresh whole blood prior to placement to mimic application in a field of active hemorrhage. The heads underwent MR imaging and the images were reviewed. Postoperative MRI images from 4 dogs undergoing brain tumor resection were retrospectively reviewed and compared to the images from the cadavers. All clinical cases and cadaveric specimens underwent surgical closure prior to MR imaging including placement of titanium mesh over the craniotomy defect with a dural graft of porcine small intestinal submucosa (SIS) sealed with Tisseel (fibrin sealant). RESULTS: The SIS and Tisseel used in the dural graft were consistently indistinguishable from the surrounding tissues on MR images. The MR imaging appearance of the remaining 4 hemostatic agents (Gelfoam, Avitene, Surgicel, and Floseal) placed on the surface or in the parenchyma of canine brain, varied with MR sequence weighting and blood saturation. CONCLUSION: Accurate evaluation of the degree of brain tumor resection on postoperative MR images requires careful differentiation between hemorrhage, residual tumor, and hemostatic agents implanted. PMID- 27658950 TI - An explorative qualitative study on acceptability of physical activity assessment instruments among primary care professionals in southern Sydney. AB - BACKGROUND: There are a substantial number of instruments for primary-care clinicians to assess physical-activity (PA). However, there are few studies that have explored the views of clinicians regarding comparative acceptability and ease of use. A better understanding of how clinicians perceive instruments could help overcome barriers, and inform future interventions. This study explored the acceptability of five PA-assessment instruments amongst a sample of Australian primary-care clinicians, including family-physicians (FP) and practice-nurses (PN). METHODS: A purposive sample of FPs (N = 9) and PNs (N = 10) from eight family-practices in southern Sydney consented to participate. Stage-1 involved semi-structured interviews with participants to select preferred instruments. An analysis of the two preferred instruments was conducted as Stage-2, to identify differences in instrument purpose and content. Stage-3 involved participants using the two instruments, selected from Stage-1, for 12-weeks. At the end of this period, semi-structured interviews were repeated to explore clinician experience. RESULTS: Clinicians indicated preferences for the GP-Physical Activity-Questionnaire and 3-Questionnaire Physical-Activity-Questionnaire. These instruments demonstrated distinct variations in content, theoretical orientation, and outcome measures. Reasons for preference included; variations in individual clinician PA levels, knowledge in PA-assessment and instrument features. CONCLUSION: Findings demonstrated two instruments as preferred. Reasons for preference related to internal characteristics of clinicians such as variations in the level of individual PA and external circumstances, such as instrument features. PMID- 27658951 TI - Papillon-Lefevre syndrome: a series of five cases among siblings. AB - BACKGROUND: Papillon-Lefevre syndrome is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressively progressing periodontitis leading to premature loss of deciduous and permanent dentition. The etiopathogenesis of the syndrome is relatively obscure, and immunologic, genetic, or possible bacterial etiologies have been proposed. CASE PRESENTATION: A series of five cases of Papillon-Lefevre syndrome among the siblings in a family is presented here: a 3-year-old Arab girl, a 4-year-old Arab boy, a 11-year-old Arab boy, a 12-year-old Arab boy, and a 14-year-old Arab boy. The patients presented with severe gingival inflammation and mobility of teeth. The clinical manifestations were typical of Papillon-Lefevre syndrome and the degree of involvement of the oral and skin conditions varied among them. CONCLUSIONS: This case series stresses the consanguinity in the family as an etiologic factor. All siblings in the family were affected with Papillon-Lefevre syndrome which makes this a rare case. A multidisciplinary approach with the active participation of a dental surgeon, dermatologist, and pediatrician is essential for the management of cases of Papillon-Lefevre syndrome. PMID- 27658953 TI - Contributions of pioneering women in indoor environment and health. PMID- 27658952 TI - Internal jugular vein versus subclavian vein as the percutaneous insertion site for totally implantable venous access devices: a meta-analysis of comparative studies. AB - BACKGROUND: A totally implantable venous access device (TIVAD) provides reliable, long-term vascular access and improves patients' quality of life. The wide use of TIVADs is associated with important complications. A meta-analysis was undertaken to compare the internal jugular vein (IJV) with the subclavian vein (SCV) as the percutaneous access site for TIVAD to determine whether IJV has any advantages. METHODS: All randomized controlled trials (RCTs) and cohort studies assessing the two access sites, IJV and SCV, were retrieved from PubMed, Web of Science, Embase, and OVID EMB Reviews from their inception to December 2015. Random effects models were used in all analyses. The endpoints evaluated included TIVAD related infections, catheter-related thrombotic complications, and major mechanical complications. RESULTS: Twelve studies including 3905 patients published between 2008 and 2015, were included. Our meta-analysis showed that incidences of TIVAD-related infections (odds ratio [OR] 0.71, 95 % confidence interval [CI] 0.48-1.04, P = 0.081) and catheter-related thrombotic complications (OR 0.76, 95 % CI 0.38-1.51, P = 0.433) were not significantly different between the two groups. However, compared with SCV, IJV was associated with reduced risks of total major mechanical complications (OR 0.38, 95 % CI 0.24-0.61, P < 0.001). More specifically, catheter dislocation (OR 0.43, 95 % CI 0.22-0.84, P = 0.013) and malfunction (OR 0.42, 95 % CI 0.28-0.62, P < 0.001) were more prevalent in the SCV than in the IJV group; however, the risk of catheter fracture (OR 0.47, 95 % CI 0.21-1.05, P = 0.065) were not significantly different between the two groups. Sensitivity analyses using fixed-effects models showed a decreased risk of catheter fracture in the IJV group. CONCLUSION: The IJV seems to be a safer alternative to the SCV with lower risks of total major mechanical complications, catheter dislocation, and malfunction. However, a large-scale and well-designed RCT comparing the complications of each access site is warranted before the IJV site can be unequivocally recommended as a first choice for percutaneous implantation of a TIVAD. PMID- 27658955 TI - Erratum to: Metformin improved health-related quality of life in ethnic Chinese women with polycystic ovary syndrome. PMID- 27658954 TI - Decreased IL7Ralpha and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin. AB - Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction. Fewer N-nucleotides were added in IGH gene rearrangements in the context of low TdT and XRCC4 expression. Moreover, fetal progenitor-B cells expressed lower levels of IL7Ralpha than their pediatric counterparts. Analysis of progenitor-B cells from IL7Ralpha-deficient patients revealed that TdT expression and N-nucleotides additions in Dh-Jh junctions were dependent on functional IL7Ralpha. Thus, IL7Ralpha affects TdT expression, and decreased expression of this receptor underlies at least in part the skewed Ig repertoire formation in fetal B-cell precursors. These new insights provide a better understanding of the formation of adaptive immunity in the developing fetus. PMID- 27658956 TI - Development of short-form and screening cutoff point of the Smartphone Addiction Inventory (SPAI-SF). AB - Smartphone addiction is considered a form of technological addiction that has attracted increasing attention. The present study developed and validated the short-form Smartphone Addiction Inventory (SPAI-SF) and established cutoff point for screening smartphone addiction based on diagnostic criteria established by psychiatric interview. A total of 268 participants completed an online survey that collected demographic data, smartphone use behaviours, and responses to the 26-item SPAI. Each participant also completed a psychiatric interview. Confirmatory factor analysis (CFA) revealed that the 10-item SPAI-SF replicated the structure of original 26-item SPAI accurately, yielding a four-factor model consisting of compulsive behaviour, functional impairment, withdrawal, and tolerance. For maximal diagnostic accuracy, a cutoff point of 24/25 best discriminated cases of smartphone addiction from diagnostic negatives. The present findings suggest that both the 26-item SPAI and SPAI-SF manifest the four constructs of behavioural addiction and the characteristics of smartphone addiction. The cutoff point determined by psychiatrists' diagnostic interview will be useful for clinical screening and epidemiologic research. PMID- 27658957 TI - Postzygotic mosaicism in basal cell naevus syndrome. AB - Basal cell naevus syndrome (BCNS) is an autosomal dominant disorder most commonly caused by a germline mutation in the Drosophila homologue of patched-1 gene (PTCH1). Here we describe a patient with clinical signs of BCNS, caused by postzygotic mosaicism of a PTCH1 mutation. We performed restriction fragment length polymorphism analysis and Droplet Digital polymerase chain reaction to determine the degree of mosaicism in different tissues of this patient. Our case shows that a relatively low-grade mosaicism can lead to clinical signs reminiscent of those caused by a germline mutation. This finding has important implications for genetic counselling and therefore is pivotal to recognize for dermatologists, as well as for clinical geneticists and clinical laboratory geneticists. PMID- 27658958 TI - ERK-dependent mTOR pathway is involved in berberine-induced autophagy in hepatic steatosis. AB - Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem and is considered as a hepatic manifestation of metabolic syndrome. Increasing evidence demonstrates that berberine (BBR), a natural plant alkaloid, is beneficial for obesity-associated NAFLD. However, the mechanisms about how BBR improves hepatic steatosis remain uncertain. Recently, some reports revealed that enhanced autophagy could decrease hepatic lipid accumulation. In this study, we first established a high-fed diet (HFD) mice model and oleate-palmitate-induced lipotoxicity hepatocytes to explore the association among BBR, autophagy and hepatic steatosis. Our data demonstrated that BBR had profound effects on improving hepatic lipid accumulation both in vivo and in vitro, and led to high autophagy flux. The molecular alterations proceeding these changes were characterized by inhibition of the ERK/mTOR pathway. These findings suggest an important mechanism for the positive effects of BBR on hepatic steatosis, and may provide new evidence for the clinical use of BBR in NAFLD. PMID- 27658959 TI - Prolactin receptor in breast cancer: marker for metastatic risk. AB - Prolactin and prolactin receptor signaling and function are complex in nature and intricate in function. Basic, pre-clinical and translational research has opened up our eyes to the understanding that prolactin and prolactin receptor signaling function differently within different cellular contexts and microenvironmental conditions. Its multiple roles in normal physiology are subverted in cancer initiation and progression, and gradually we are teasing out the intricacies of function and therapeutic value. Recently, we observed that prolactin has a role in accelerating the time to bone metastasis in breast cancer patients and identified the mechanism by which prolactin stimulated breast cancer cell mediated lytic osteoclast formation. The possibility that the prolactin receptor is a marker for metastasis, and specifically bone metastasis, is one that may have to be put into the context of the different variants of prolactin, different prolactin receptor isoforms and intricate signaling pathways that are regulated by the microenvironment. The more complete the picture, the better one can test biomarker identity and design clinical trials to test therapeutic intervention. This review will cover the recent advances and highlight the complexity of prolactin receptor biology. PMID- 27658960 TI - Molecular transport through large-diameter DNA nanopores. AB - DNA-based nanopores are synthetic biomolecular membrane pores, whose geometry and chemical functionality can be tuned using the tools of DNA nanotechnology, making them promising molecular devices for applications in single-molecule biosensing and synthetic biology. Here we introduce a large DNA membrane channel with an ~4 nm diameter pore, which has stable electrical properties and spontaneously inserts into flat lipid bilayer membranes. Membrane incorporation is facilitated by a large number of hydrophobic functionalizations or, alternatively, streptavidin linkages between biotinylated channels and lipids. The channel displays an Ohmic conductance of ~3 nS, consistent with its size, and allows electrically driven translocation of single-stranded and double-stranded DNA analytes. Using confocal microscopy and a dye influx assay, we demonstrate the spontaneous formation of membrane pores in giant unilamellar vesicles. Pores can be created both in an outside-in and an inside-out configuration. PMID- 27658961 TI - Erratum: Detecting a hierarchical genetic population structure via Multi-InDel markers on the X chromosome. PMID- 27658962 TI - Interleukin-25 Induces Resistance Against Intestinal Trematodes. AB - Echinostoma caproni is an intestinal trematode that has been extensively used as an experimental model to investigate the factors determining the resistance to intestinal helminths or the development of chronic infections. ICR mice are permissive hosts for E. caproni in which chronic infections are developed, concomitantly with local Th1 responses, elevated levels of local IFN-gamma, inflammation and antibody responses. However, mice develop partial resistance to homologous challenge infections after cure of a primary infection, which converts this subject into an adequate model for the study of the mechanisms generating resistance against intestinal helminths. The purpose of the present study was to compare the immune response induced in primary and secondary infections to elucidate the factors determining the different outcome of the infection in each type of infection. The results obtained indicate that susceptibility is determined by the lack of IL-25 expression in response to primary infection. In contrast, infection in an environment with elevated levels of IL-25, as occurs in challenge infection, results in a Th2 phenotype impairing parasite survival. This was confirmed by treatment of naive mice with exogenous IL-25 and subsequent infection. Changes induced in goblet cell populations and mucin glycosylation could be implicated in resistance to infection. PMID- 27658963 TI - Selected plantar pressure characteristics associated with the skating performance of national in-line speed skaters. AB - In order to help coaches analyse the techniques of professional in-line speed skaters for making the required fine adjustments and corrections in their push off work, this study analysed the specific plantar pressure characteristics during a 300-m time-trial test. Fourteen elite in-line speed skaters from the national team were recruited in this study. The total completion time of the 300 m time-trial test, duration of each skating phase, and plantar pressure distribution were measured. The correlation between plantar pressure distribution and skating performance was assessed using Pearson correlation analyses. The results showed that the contact time of the total foot and force-time integral (FTI) in the medial forefoot were significantly correlated with the duration of the start phase, and the FTIs in the medial forefoot of the gliding (left) leg and lateral forefoot of the pushing (right) leg were significantly correlated with the duration of the turning phase. The maximum force in the medial heel, medial forefoot, and median forefoot and the FTI in the medial heel and medial forefoot were significantly correlated with the duration of the linear acceleration phase. The results suggest that a correct plantar loading area and push-off strategy can enhance the skating performance. PMID- 27658964 TI - New insights into the Shwachman-Diamond Syndrome-related haematological disorder: hyper-activation of mTOR and STAT3 in leukocytes. AB - Shwachman-Diamond syndrome (SDS) is an inherited disease caused by mutations of a gene encoding for SBDS protein. So far little is known about SBDS exact function. SDS patients present several hematological disorders, including neutropenia and myelodysplastic syndrome (MDS), with increased risk of leukemic evolution. So far, the molecular mechanisms that underlie neutropenia, MDS and AML in SDS patients have been poorly investigated. STAT3 is a key regulator of several cellular processes including survival, differentiation and malignant transformation. Moreover, STAT3 has been reported to regulate neutrophil granulogenesis and to induce several kinds of leukemia and lymphoma. STAT3 activation is known to be regulated by mTOR, which in turn plays an important role in cellular growth and tumorigenesis. Here we show for the first time, to the best of our knowledge, that both EBV-immortalized B cells and primary leukocytes obtained from SDS patients present a constitutive hyper-activation of mTOR and STAT3 pathways. Interestingly, loss of SBDS expression is associated with this process. Importantly, rapamycin, a well-known mTOR inhibitor, is able to reduce STAT3 phosphorylation to basal levels in our experimental model. A novel therapeutic hypothesis targeting mTOR/STAT3 should represent a significant step forward into the SDS clinical practice. PMID- 27658965 TI - Stereological analyses of the whole human pancreas. AB - The large size of human tissues requires a practical stereological approach to perform a comprehensive analysis of the whole organ. We have developed a method to quantitatively analyze the whole human pancreas, as one of the challenging organs to study, in which endocrine cells form various sizes of islets that are scattered unevenly throughout the exocrine pancreas. Furthermore, the human pancreas possesses intrinsic characteristics of intra-individual variability, i.e. regional differences in endocrine cell/islet distribution, and marked inter individual heterogeneity regardless of age, sex and disease conditions including obesity and diabetes. The method is built based on large-scale image capture, computer-assisted unbiased image analysis and quantification, and further mathematical analyses, using widely-used software such as Fiji/ImageJ and MATLAB. The present study includes detailed protocols of every procedure as well as all the custom-written computer scripts, which can be modified according to specific experimental plans and specimens of interest. PMID- 27658968 TI - N-doped graphene layers encapsulated NiFe alloy nanoparticles derived from MOFs with superior electrochemical performance for oxygen evolution reaction. AB - Water splitting, an efficient approach for hydrogen production, is often hindered by unfavorable kinetics of oxygen evolution reaction (OER). In order to reduce the overpotential, noble metal oxides-based electrocatalysts like RuO2 and IrO2 are usually utilized. However, due to their scarcity, the development of cost effective non-precious OER electrocatalysts with high efficiency and good stability is urgently required. Herein, we report a facile one-step annealing of metal-organic frameworks (MOFs) strategy to synthesize N-doped graphene layers encapsulated NiFe alloy nanoparticles (NiFe@C). Through tuning the nanoparticle size and calcination temperature, NiFe@C with an average size of around 16 nm obtained at 700 degrees C exhibits superior OER performance with an overpotential of only 281 mV at 10 mA cm-2 and high durability. The facile synthesis method and excellent electrochemical performance show great potential of NiFe@C in replacing the precious metal-based electrocatalysts in the OER. PMID- 27658967 TI - Protein-DNA interfaces: a molecular dynamics analysis of time-dependent recognition processes for three transcription factors. AB - We have studied the dynamics of three transcription factor-DNA complexes using all-atom, microsecond-scale MD simulations. In each case, the salt bridges and hydrogen bond interactions formed at the protein-DNA interface are found to be dynamic, with lifetimes typically in the range of tens to hundreds of picoseconds, although some interactions, notably those involving specific binding to DNA bases, can be a hundred times longer lived. Depending on the complex studied, this dynamics may or may not lead to the existence of distinct conformational substates. Using a sequence threading technique, it has been possible to determine whether DNA sequence recognition is sensitive or not to such conformational changes, and, in one case, to show that recognition appears to be locally dependent on protein-mediated cation distributions. PMID- 27658969 TI - Enhancing the Spin-Orbit Coupling in Fe3O4 Epitaxial Thin Films by Interface Engineering. AB - By analyzing the in-plane angular dependence of ferromagnetic resonance linewidth, we show that the Gilbert damping constant in ultrathin Fe3O4 epitaxial films on GaAs substrate can be enhanced by thickness reduction and oxygen vacancies in the interface. At the same time, the uniaxial magnetic anisotropy due to the interface effect becomes significant. Using the element-specific technique of X-ray magnetic circular dichroism, we find that the orbital-to-spin moment ratio increases with decreasing film thickness, in full agreement with the increase in the Gilbert damping obtained for these ultrathin single-crystal films. Combined with the first-principle calculations, the results suggest that the bonding with Fe and Ga or As ions and the ionic distortion near the interface, as well as the FeO defects and oxygen vacancies, may increase the spin orbit coupling in ultrathin Fe3O4 epitaxial films and in turn provide an enhanced damping. PMID- 27658966 TI - ADAR1 restricts LINE-1 retrotransposition. AB - Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosines to inosines in double-stranded RNAs. ADAR1 was demonstrated to be functional on different viruses exerting either antiviral or proviral effects. Concerning HIV-1, several studies showed that ADAR1 favors viral replication. The aim of this study was to investigate the composition of the ADAR1 ribonucleoprotein complex during HIV-1 expression. By using a dual-tag affinity purification procedure in cells expressing HIV-1 followed by mass spectrometry analysis, we identified 14 non-ribosomal ADAR1-interacting proteins, most of which are novel. A significant fraction of these proteins were previously demonstrated to be associated to the Long INterspersed Element 1 (LINE1 or L1) ribonucleoparticles and to regulate the life cycle of L1 retrotransposons that continuously re-enter host-genome.Hence, we investigated the function of ADAR1 in the regulation of L1 activity.By using different cell-culture based retrotransposition assays in HeLa cells, we demonstrated a novel function of ADAR1 as suppressor of L1 retrotransposition. Apparently, this inhibitory mechanism does not occur through ADAR1 editing activity. Furthermore, we showed that ADAR1 binds the basal L1 RNP complex. Overall, these data support the role of ADAR1 as regulator of L1 life cycle. PMID- 27658971 TI - [First Experience with Femtosecond Laser Presbyopia Correction Method INTRACOR]. AB - : We report the first experience with presbyopia correcting femtosecond laser surgical procedure INTRACOR. This procedure is so far the only one that is made purely intrastromally without generating a wound connected to corneal surface or anterior chamber.Presbyopia - caused by physiological aging and decreasing elasticity of the lens, impairs patients accommodative ability. In the case of the method INTRACOR, presbyopia is corrected by steepening of corneal curvature in the central optical zone. Procedure is usually performed only in the non dominant eye. METHODS: Intracor procedure was performed in 10 eyes of 10 patients (3 women and 7 men, aged 47-58 years). All procedures were performed with the femtosecond laser VICTUS (Bausch - Lomb, USA) in the non-dominant eye by an experienced surgeon. RESULTS: One-year follow-up. Mean monocular uncorrected near visual acuity (UNVA) improved from 0.2 +/- 0.1 before surgery to 0.7 +/- 0.3 after treatment (mean improvement of four lines). Mean near uncorrected binocular visual acuity (UNBVA) improved from a mean preoperative value of 0.23 +/- 0.08 to a mean postoperative value of 0.8 +/- 0.22 (mean improvement of about 5 lines). The mean monocular uncorrected distance visual acuity (UDVA) was 0.9 +/- 0.1 before surgery and 0.8 +/- 0.3 after treatment (average loss of 1 line). The mean binocular uncorrected distance visual acuity improved from 1.0 +/- 0,1 to 1,3 +/- 0.3 after surgery. All patients had improvements in near vision. In 3 patient, monocular distance vision improved, in 6 patient improved binocular distance vision. We observed statistically significant decrease (mean loss of 1 line) of monocular best corrected distance visual acuity (BCDVA). Patients subjectively reported satisfaction with the quality of vision achieved for near and distance and high levels of spectacle independence under good lighting conditions.The results shows that INTRACOR method is well suitable for low hyperopic patients, who because of good distance visual acuity are not good candidates for refractive lens exchange with multifocal intraocular lens implantation. KEY WORDS: presbyopia, Intracor, intrastromal, femtosecond laser. PMID- 27658970 TI - Factors that can predict pain with walking, 12 months after total knee arthroplasty. AB - Background and purpose - Functional limitations after total knee arthroplasty (TKA) are common. In this longitudinal study, we wanted to identify subgroups of patients with distinct trajectories of pain-related interference with walking during the first year after TKA and to determine which demographic, clinical, symptom-related, and psychological characteristics were associated with being part of this subgroup. Patients and methods - Patients scheduled for primary TKA for osteoarthritis (n = 202) completed questionnaires that evaluated perception of pain, fatigue, anxiety, depression, and illness on the day before surgery. Clinical characteristics were obtained from the medical records. Interference of pain with walking was assessed preoperatively, on postoperative day 4, and at 6 weeks, 3 months, and 12 months after TKA. Results - Using growth mixture modeling, 2 subgroups of patients were identified with distinct trajectories of pain-related interference with walking over time. Patients in the Continuous Improvement class (n = 157, 78%) had lower preoperative interference scores and reported a gradual decline in pain-related interference with walking over the first 12 months after TKA. Patients in the Recurrent Interference class (n = 45, 22%) reported a high degree of preoperative pain-related interference with walking, initial improvement during the first 3 months after TKA, and then a gradual increase-returning to preoperative levels at 12 months. Patients in the Recurrent Interference class had higher preoperative pain, fatigue, and depression scores, and poorer perception of illness than the Continuous Improvement class. Interpretation - 1 in 5 patients did not improve in pain related interference with walking at 12 months after TKA. Future studies should test the efficacy of interventions designed to modify preoperative characteristics. PMID- 27658972 TI - [Outcomes of Trifocal Toric Lens Implantation in Cataract Patients]. AB - AIM: The aim of our study was to evaluate the outcome of cataract surgeries with implantation of intraocular trifocal toric lens, and to study the accuracy of astigmatism correction, lens rotational stability, and safety of the procedures. PATIENTS AND METHODS: Our study comprised 22 eyes of 16 patients who underwent unilateral or bilateral implantation of AT LISA tri toric 939MP, or its implantation in combination with AT LISA tri 839MP. Mean patient age was 58 +/- 11 years (39 to 75 years). Mean follow-up was 5 months. Evaluated parameters were preoperative and postoperative decimal corrected (CDVA) and uncorrected (UDVA) distance visual acuity. Uncorrected near (UNVA) and intermediate (UIVA) visual acuity was obtained with Jaeger optotypes. Furthermore, we studied manifest refraction, amount of corneal astigmatism, implanted lens position, and potential complications. Using two types of questionnaires we surveyed patients on their subjective satisfaction with vision. RESULTS: Spherical equivalent changed from preoperative -1.32 +/- 4.05 D (-9.25 to 4.00 D) to postoperative -0.23 +/- 0.21 D (-0.75 to 0.00 D). Preoperative corneal astigmatism was -1.97 +/- 0.76 D (-4.02 to -1.01 D), manifest astigmatism was -1.70 +/- 1.26 D. After the surgery, manifest astigmatism significantly improved to -0.34 +/- 0.37 D (p<0.001). Mean monocular UDVA increased from 0.26 +/- 0.18 (0.05 to 0.60) to postoperative 0.88 +/- 0.13 (0.60 to 1.00) (p<0.001). CDVA also improved significantly, from 0.57 +/ 0.24 to a final value of 1.02 +/- 0.07 (p<0.001). Mean postoperative monocular UNVA was Jaeger 1-2, UIVA corresponded to Jaeger 3-4.No serious complications were recorded. Based on the outcome of questionnaires, all patients are satisfied with their vision and they are independent of spectacles. CONCLUSION: In the present study we have obtained very good functional outcomes of vision at far, near and intermediate in cataract patients after trifocal AT LISA tri toric lens implantation. Also, total astigmatism in studied eyes was substantially reduced. The treatment led to a high subjective satisfaction of patients and to their independence of spectacles. KEY WORDS: trifocal toric intraocular lens, cataract, astigmatism, refractive outcomes, patient subjective satisfaction. PMID- 27658973 TI - [Objective Assessment of Postoperative Results of Intraocular Lenses]. AB - PURPOSE: To prospectively compare postoperative results of two premium intraocular lenses EnVISTA (Bausch and Lomb) and AcrySof IQ (Alcon), focussing on glistenings and posterior capsule opacification. The evaluation of glistenings was done using Image J software and posterior capsule opacifications were quantified with OSCA system. METHODS: Twenty patients (7 men and 13 women) with bilateral cataract were included. EnVista intraocular lens (IOL) was implanted in one eye and AcrySof IQ IOL in the second eye of each patient. Objective evaluation methods were used for assessment. Glistenings was quantified with ImageJ software and PCO using the Open-Access Systematic Capsule Assessment (OSCA) system (Devised by Aslam TM, Edinburgh, United Kingdom). Complete ophthtalmological evaluation including evaluation after pupil dilatation was done and digital images of intraocular lenses were obtained. The results of 2-, 4-, 6- and 12-month follow-up were compared. RESULTS: Twenty patients were analyzed 2 months, 16 patients 4 months, 14 patients 6 months and 13 patients 12 months after cataract surgery. There was only minimal difference in best corrected visual acuity between EnVista and AcrySof group. The glistenings in the EnVista IOLs was objectively lower than in the AcrySof IOLs during whole follow-up period. In contrast to PCO, in eyes with AcrySof IOL was lower PCO score. CONCLUSION: Development of new materials and techniques of cataract surgery is the topic of ophthtalmologists worldwide. Reduction of glistenings and PCO is one of the main aims, objective measurements is important part of assessment of postoperative results after cataract surgery. KEY WORDS: glistenings, posterior capsule opacification, EnVista, AcrySof IQ, Image J software, OSCA system. PMID- 27658974 TI - [Local Rotating Flaps in Oculoplastic Surgery]. AB - AIM: In the contemporary medicine, strong emphasis is put on early closing of body surface defects, which contributes to good and early healing, but, of course, closes the entrance gate for possible infection as well. The easiest closing of the defect is the direct suture of the emerged wound. But some defects are of such an extent, so their closure is necessary to handle other way than simple suture, e.g. by rotating flap plastic surgery. In the paper are evaluated results of flap surgery technique in 56 patients. MATERIAL AND METHODS: It is a retrospective overview of 56 patients operated on by the author in the years 2011 2012, in whom the rotating flap plastic surgery was used as surgery technique. In 46 patients, the reason of flap plastic surgery technique was tumor of the eyelids. In 35 patients, it was due to the basalioma of the lower eyelid, in 8 patients due to the basalioma of the upper eyelid, and in three patients due to the basalioma of the medial cantus region. In 10 patients, the reason of the surgery was ectropion of the lower eyelid, and in two of them bilaterally. The paper is supplemented by surgical procedures photographs, and by a table, with detailed analysis of the sizes of tumors and corresponding flaps as well. RESULTS: According to the experience with 56 rotating flap plastic surgeries, performed by author during the period of two years at the Department of Ophthalmology, Masaryk Hospital in Usti nad Labem, Czech Republic. E.U., the results of the use of rotating skin flaps in 46 eyelids basalioma, of correcting 12 ectropions of the lower eyelid, and reliability of the tumors excision with 2 mm surrounding healthy tissue rim were followed-up. Using the mentioned surgery technique, it was possible in all patients to secure the closing of the eyelid defect, or to return to normal and correct anatomical position of the eyelids in ectropions. In two patients with basalioma of the lower eyelid, the additional technique of lateral cantotomy was used to relieve the tension in the wound. Statistical results of recurrences number in tumors excisions with 2 mm safety margin in to the healthy tissue confirm the relative safety of such wide excision, and our results (4.34 %) differ only slightly from the results published in the literature (4.0 %). KEY WORDS: flap plastic surgery, basalioma, ectropion. PMID- 27658975 TI - [Possibility of 3D Printing in Ophthalmology - First Experiences by Stereotactic Radiosurgery Planning Scheme of Intraocular Tumor]. AB - : Nowadays 3D printing allows us to create physical objects on the basis of digital data. Thanks to its rapid development the use enormously increased in medicine too. Its creations facilitate surgical planning processes, education and research in context of organ transplantation, individualization prostheses, breast forms, and others.Our article describes the wide range of applied 3D printing technology possibilities in ophthalmology. It is focusing on innovative implementation of eye tumors treatment planning in stereotactic radiosurgery irradiation.We analyze our first experience with 3D printing model of the eye in intraocular tumor planning stereotactic radiosurgery. KEY WORDS: 3D printing, model, Fused Deposition Modelling, stereotactic radiosurgery, prostheses, intraocular tumor. PMID- 27658976 TI - [Technical Options of Documentation of the Anterior Segment and the eye Fundus Findings within Mission]. AB - : Documentation of the anterior segment and the eye fundus with instruments that enable quality precision diagnostics is a common and important part of screening in humanitarian ophthalmology projects. It is the essential element in diagnosis, monitoring and management of eye diseases. In sub saharan countries within the screening for ophthalmologist are not available the modern technologies such as biomicroscope (slit lamp) or fundus camera. We describe our experience with photographs of anterior segment of the eye by using digital camera and Smartphone. The documentation of the eye fundus was recorded through 20D Volk spherical lens to Smartphone. MATERIAL AND METHODS: Within the screening projects in collaboration with St. Elisabeth University of Health and Social Sciences for eye diseases in the year 2014 in Bigugu, Rwanda and in 2015 in Mapuordit, South Sudan, we examined patients who were unable to reach ophthalmologic care. We used a flashlight, a direct ophthalmoscope, tables to determine visual acuity on illiterate, Schiotz tonometer, Volk lens, Smartphone. Patients who underwent screening, and needed glasses, got from humanitarian collection already used dioptric eyeglasses or sunglasses. For documentation of the anterior segment we used a digital camera and for patients in whom it was necessary to document fundus findings detected by direct ophthalmoscopy we took the opportunity of Smartphone with 8 Mpix camera and the LED flash and Volk lens plus 20 Diopters. RESULTS: In 2014 within the project in Bigugu, Rwanda and in 2015 in Mapuordit, South Sudan, we examined patients in an improvised clinic without access to electricity.We examined in 2014 a total of 340 patients and in 2015 a total of 290 patients. Patient age was due to the unavailability of designated identification records estimated with the help of an interpreter. In both groups, the mean age of the patients was about 30 years. The most common diseases leading to blindness were cataract, trachoma, post-traumatic conditions. Infectious diseases and consequences of untreated infectious diseases were the cause of 20% of the permanent changes on the surface of the eye or the adnexa. In the group of HIV positive patients we did not mention pathological findings on the eye fundus. CONCLUSION: Anterior segment findings documentation with digital camera or mobile phone and fundus examination using a Smartphone and Volks lens with a value of plus 20D is inexpensive and manageable technique which can capture high quality and reproducible images. These techniques are suitable for photo documentation of anterior segment and also eye fundus screening within humanitarian projects of eye diseases in developing countries. KEY WORDS: anterior segment examination, eye fundus examination, Smartphone, digital camera, humanitarian screening projects of eye diseases. PMID- 27658977 TI - [Orbital Exenteration in Patient with Metastatic Choroidal Melanoma - a Case Report]. AB - INTRODUCTION: Uveal melanoma is the most common primary intraocular tumour in adults in Caucasians and in 75% is arising from choroid. It threatens not only the patients loss of vision and eye, but also 50% of patients after 5-year interval after therapy die due to distant metastases. The treatment of small and medium-sized melanoma are methods preserving eye globe. Almost half of the total number of patients is still unavoidable enucleation. Considerably rarer is indicated exenteration of an orbit. These tumors metastasize only hematogenous, while the most frequent place of localization of distant metastases is the liver. Generalized disease prognosis is poor, and our current treatment options in this stage are ineffective. MATERIAL AND METHODS: Case report of 59 years old patient with choroidal melanoma stage T4 N1 M1 massively infiltrating the orbit. At the time of diagnosis of the primary tumor distant metastases were present. The patient underwent exenteration of the orbit and systemic chemotherapy. DISCUSSION: Although choroidal melanomas with extrascleral extension and infiltration into the orbit have no better prognosis after exenteration of the orbit, surgery is providing us local tumour control. Good cosmetic effect after this mutilating procedure is offered by individually made prosthesis (epithesis). All patients with uveal melanoma require lifelong dispensation, distant metastases may occur even after many years. In the treatment of generalized disease is available systemic chemotherapy and immunotherapy only palliative. The best effect on survival has complete surgical resection of single metastasis. Uveal melanoma has a different genetic profile as cutaneous melanoma. The biological nature of uveal melanoma seems to be the key to determining risk patients, as well as the development of targeted systemic therapy. CONCLUSION: Treatment of patients with generalized large uveal melanoma with extrascleral extension is difficult. A better understanding of biological interest may be the key to the detection of patients at higher risk of distant metastases formation, and to an effective systemic treatment. KEY WORDS: large uveal melanoma, extrascleral extension, orbital exenteration, the treatment of generalized disease. PMID- 27658978 TI - Modular aortic valve prosthesis for transcatheter aortic valve implantation: a novel concept with a new implantation method. AB - Transcatheter aortic valve implantation (TAVI) is a relatively new medical intervention. Research on dedicated TAVI devices is an exciting and dynamic field to be explored by professionals involved in technological innovation. The authors describe in this article the first engineering concept and part of the US Patent of a new valve prosthesis. Divided into two pieces to be separately implanted using a single catheter by means of an innovative technique, this device aims at reducing prosthesis and delivery catheter profile. Miniaturization of the valve and delivery system is probably the best solution to reduce the morbidity and mortality that derive from vascular complications associated with TAVI. PMID- 27658979 TI - High-dose dexamethasone or oral prednisone for immune thrombocytopenia? PMID- 27658981 TI - Acute leukodystrophy: elevated risk for neurocognitive impairment and imaging abnormalities. PMID- 27658982 TI - High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis. AB - BACKGROUND: Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response. METHODS: We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 * 109/L) and complete (platelets >100 * 109/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model. FINDINGS: Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1.16, 95% CI 0.79-1.71; p=0.44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1.22, 95% CI 1.00-1.49; p=0.048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children. INTERPRETATION: In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count. FUNDING: Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada. PMID- 27658980 TI - Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis. AB - BACKGROUND: Leukoencephalopathy is observed in some children undergoing chemotherapy for acute lymphoblastic leukaemia, although its effects on long-term outcomes is unknown. This study examines the associations between acute leukoencephalopathy and neurobehavioural, neurocognitive, and brain white matter imaging outcomes in long-term survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy without cranial radiation. METHODS: In this longitudinal analysis, we used data of children with acute lymphoblastic leukaemia at St Jude Children's Research Hospital (Memphis, TN, USA) who had been treated between June 1, 2000, and Oct 31, 2010. Eligible patients were diagnosed with non-B-cell acute lymphoblastic leukaemia, aged at least 8 years, and survivors with at least 5 years since their initial diagnosis. Brain MRIs obtained during active therapy were systematically coded for leukoencephalopathy using Common Terminology Criteria for Adverse Event version 4. At least 5 years after their diagnosis, survivors completed neurocognitive testing, another brain MRI, and their parents completed neurobehavioural ratings of their child (Behavior Rating Inventory of Executive Function [BRIEF]). Follow-up MRI included diffusion tensor imaging to assess white matter integrity, with indices of fractional anisotropy, axial diffusivity, and radial diffusivity from frontal lobes, parietal lobes, and in the frontostriatal tract. The neuroradiologist, who assessed abnormal MRIs, was masked to both group assignment of survivors and the neurobehavioural and neurocognitive outcomes. The primary outcomes were neurobehavioural function, assessed from completed BRIEF, and neurocognitive performance, measured by direct neurocognitive tests (Delis-Kaplan Executive Function System, Wechsler Intelligence Scale for Children-IV/Wechsler Adult Intelligence Scale-III, Rey-Osterrieth Complex Figure Test, and Lafayette Grooved Pegboard Test). This study had completed enrolment in October, 2014, and is registered as an observational study at ClinicalTrials.gov, number NCT01014195. FINDINGS: Between Feb 18, 2010, and Oct 22, 2014, 210 (70%) of 301 eligible survivors participated in our study of whom 190 were evaluable, 162 had an MRI. 56 participants had quantitative brain imaging data and were included in evaluable population analyses. 51 (27%) of the 190 evaluable participants had acute leukoencephalopathy. Compared with population norms, survivors were reported to have more neurobehavioural problems with working memory, organisation, initiation, and planning (p<0.001 for all). Survivors had worse scores than the general population on direct measures of memory span, processing speed, and executive function (p<0.05 for all). Survivors with a history of acute leukoencephalopathy had more neurobehavioural problems than survivors with no history of leukoencephalopathy on organisation (adjusted T-score 56.2 [95% CI 53.3-59.1] vs 52.2 [50.4-53.9], p=0.020) and initiation (55.5 [52.7-58.3] vs 52.1 [50.4-53.8], p=0.045). Survivors with acute leukoencephalopathy also had reduced white matter integrity in the frontostriatal tract at follow-up: lower fractional anisotropy (p=0.069), higher axial diffusivity (p=0.020), and higher radial diffusivity (p=0.0077). A one-unit change in the radial diffusivity index corresponded with a 15.0 increase in raw score points on initiation, 30.3 on planning, and 28.0 on working memory (p<0.05 for all). INTERPRETATION: Acute leukoencephalopathy during chemotherapy treatment, without cranial radiation, for childhood acute lymphoblastic leukaemia predicted higher risk for long-term neurobehavioural problems and reduced white matter integrity in frontal brain regions. Survivors of childhood acute lymphoblastic leukaemia might benefit from preventive cognitive or behavioural interventions, particularly those who develop acute leukoencephalopathy. FUNDING: National Institute of Mental Health, National Cancer Institute, American Lebanese Syrian Associated Charities. PMID- 27658983 TI - A HuR/TGF-beta1 feedback circuit regulates airway remodeling in airway smooth muscle cells. AB - BACKGROUND: Asthma is a worldwide health burden with an alarming prevalence. For years, asthma-associated airway injury remains elusive. Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine that has been shown to be involved in the synthesis of the matrix molecules associated with airway remodeling. Human antigen R (HuR), the member of the Hu RNA-binding protein family, can bind to a subset of short-lived mRNAs in their 3' untranslated regions (UTR). However, the functional roles and relevant signaling pathways of HuR in airway remodeling have not been well illustrated. Thus, we aim to explore the relationship between HuR and TGF-beta1 in platelet derived growth factor(PDGF)-induced airway smooth muscle (ASM) cells and asthmatic animal. METHODS: Cultured human ASM cells were stimulated by PDGF for 0, 6, 12 and 24 h. Western blotting, RT-PCR and immunofluoresence were used to detect the expression of HuR, TGF-beta1, alpha-smooth muscle actins (alpha-SMA) and collagen type I (Col-I). Then knockdown of HuR, flow cytomerty was used to detect the morphological change and western blotting for functionally change of ASM cells. Furthermore, the interference of TGF-beta1 and exogenous TGF-beta1 were implemented to testify the influence on HuR. A murine OVA-driven allergic model based on sensitization and challenge was developed. The inflammatory response was measured by bronchoalveolar lavage fluid (BALF), airway damage was analyzed by hematoxylin and eosin staining, airway remodeling was assessed by sirius red staining and periodic acid-schiff staining, the expression level of HuR, TGF beta1 and alpha-SMA were measured by RT-PCR, western blotting and immunohistochemistry. RESULTS: Here, we found that PDGF elevated HuR expression both at mRNA and protein level in cultured ASM cells at a time-dependent manner, which was simultaneously accompanied by the enhanced expression of TGF-beta1, alpha-SMA and Col-I. Further study revealed that the knockdown of HuR significantly increased the apoptosis of ASM cells and dampened TGF-beta1, Col-I and alpha-SMA expression. However, interfering TGF-beta1 with siRNA or extra addition of TGF-beta1, HuR could restore its production as well as Col-I. Compared with normal mice stimulating with PBS, OVA-induced mice owned high amount of inflammatory cells, such as eosinophils, lymphocytes and neutrophils except macrophages. HE staining showed accumulation of inflammatory cells surrounding bronchiole and sirius red staining distinguished collagen type I and III deposition around the bronchiole. Higher abundance of HuR, TGF-beta1 and alpha-SMA were verified in OVA-induced mice than PBS-induced mice by RT-PCR, western blotting and immunohistochemistry. CONCLUSIONS: A HuR/TGF-beta1 feedback circuit was established to regulate airway remodeling in vivo and in vitro and targeting this feedback has considerable potential for the intervention of asthma. PMID- 27658985 TI - Routine radiographs one day after anterior cervical discectomy and fusion are neither necessary nor cost-effective. AB - OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) is a common operative treatment of compressive pathology of the cervical spinal cord, when caused by one or more degenerated intervertebral discs or related osteophytes. In addition to intra-operative radiographs to confirm spinal level before discectomy and implant position after insertion, traditional practice is to obtain post operative antero-posterior and lateral plain radiographs (XR) before hospital discharge, despite a paucity of evidence supporting their benefit to patient care. Minimising unnecessary radiation to radiosensitive neck structures is desirable, and furthermore, with increasing financial pressure on healthcare resources, routine investigations should be clinically justified and evidence based. We aim to compare the utility of routine post-operative cervical spine X rays following ACDF. METHODS: We compare two groups of consecutive patients undergoing ACDF in a single UK neurosurgical centre. The first group (n = 109) received routine post-operative XR imaging, and the second group (n = 113) received radiographs only when clinically indicated. RESULTS: There were no differences in post-operative complication rates (4.6% vs. 5.3%), or requirement for further imaging or of further operative intervention (1.8% vs. 0.9%). The group that did not have routine post-operative radiographs had a significantly shorter stay in hospital (median two days vs. three days). There were no patients in either group where post-operative XR changed clinical management and mandated revision surgery or further imaging. All cases requiring surgery or further imaging were identified by clinical deterioration. CONCLUSIONS: We suggest that the practice of obtaining routine radiographs of the cervical spine following ACDF should be abandoned, unless there is a clear clinical indication. PMID- 27658984 TI - Role of CaMKII in Ang-II-dependent small artery remodeling. AB - Angiotensin-II (Ang-II) is a well-established mediator of vascular remodeling. The multifunctional calcium-calmodulin-dependent kinase II (CaMKII) is activated by Ang-II and regulates Erk1/2 and Akt-dependent signaling in cultured smooth muscle cells in vitro. Its role in Ang-II-dependent vascular remodeling in vivo is far less defined. Using a model of transgenic CaMKII inhibition selectively in smooth muscle cells, we found that CaMKII inhibition exaggerated remodeling after chronic Ang-II treatment and agonist-dependent vasoconstriction in second-order mesenteric arteries. These findings were associated with increased mRNA and protein expression of smooth muscle structural proteins. As a potential mechanism, CaMKII reduced serum response factor-dependent transcriptional activity. In summary, our findings identify CaMKII as an important regulator of smooth muscle function in Ang-II hypertension in vivo. PMID- 27658987 TI - Physicochemical properties of direct compression tablets with spray dried and ball milled solid dispersions of tadalafil in PVP-VA. AB - The aim of this research was to develop immediate release tablets comprising solid dispersion (IRSDTs) of tadalafil (Td) in a vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA), characterized by improved dissolution profiles. The solid dispersion of Td in PVP-VA (Td/PVP-VA) in a weight ratio of 1:1 (w/w) was prepared using two different processes i.e. spray drying and ball milling. While the former process has been well established in the formulation of IRSDTs the latter has not been exploited in these systems yet. Regardless of the preparation method, both Td/PVP-VA solid dispersions were amorphous as confirmed by PXRD, DSC and FTIR. However, different morphology of particles (SEM) resulted in differences in water apparent solubility and disk intrinsic dissolution rate (DIDR). Both solid dispersions and crystalline Td were successfully made into directly compressible tablets at three doses of Td, i.e. 2.5mg, 10mgand20mg, yielding nine different formulations (D1-D9). Each of the lots met the requirements set by Ph.Eur. and was evaluated with respect to appearance, diameter, thickness, mass, hardness, friability, disintegration time and content of Td. IRSDTs performed as supersaturable formulations and had significantly improved water dissolution profiles in comparison with equivalent tablets containing crystalline Td and the marketed formulations. Tablets with both spray dried and ball milled Td/PVP-VA revealed the greatest improvement in dissolution depending on the investigated doses, i.e. 2.5mgand20mg, respectively. Also, dissolution of Td from Td/PVP-VA delivered in different forms occurred in the following order: powders>tablets>capsules. PMID- 27658988 TI - [Homicide-suicide: Clinical review and psychological assumptions]. AB - OBJECTIVES: Suicide-homicide could be defined as a "suicidal" behaviour, which also includes the death of at least one other individual and sometimes up to hundreds. This literature review intends to highlight some characteristic features that might be found amongst the various types of suicide-homicide. It is a complex phenomenon which can occur in different situations, from a familial and somehow intimate setting (filicide, uxoricide, marital homicide...) to a public one (workplace shooting, school shooting), including a wide range of victims, from a single victim in marital cases of suicide-homicide to hundreds of victims in certain types, such as suicide by aircraft or warrior-like multi-homicids in terrorist acts. This literature review offers a combination of data emanating from scientific publications and case studies from our practices in an attempt to insulate some common factors. A thorough examination of the offenses unravels complex processes, ideations, M.O and peculiar cognitive impairments in which the familial suicide-homicide could be rooted. Mass murders might be caused also by a psychopathological alloy, made of Grandiose Self and sub-depressive and even paranoid ideations. Concerning the terrorism and multi-homicide-suicide, this is far more complex phenomenon and is defined by a group-process enrolment and ideological conviction. Beyond epidemiological studies, both descriptive and statistical, this paper's objective is to isolate a hypothesis about a psychopathological ground from which a criminological mechanism could emerge. Despite the lack of blatant psychosis, some traits might be identified in suicide homicide cases - such as paranoid, psychopathic, narcissistic, melancholic - which can intertwine, potentiate one with another forming a distorted view of the world. The offense dynamic is possibly composed of preparatory behaviours, triggers, the use of death as a narcissistic support, identity choices... METHODS: The data were collected from scientific publications, personal cases, and open source. RESULTS: Despite the variety of behaviours included in this typology, we were able to identify a few mechanisms that could be found in two types of suicide-homicide [Private suicide-homicide (within the family circle) vs. Public space suicide-homicide (suicide by aircraft, school shooting...)]. DISCUSSION: Suicide-homicide phenomenon is the result of the interaction of societal, ideological, psychopathological and criminological elements which burst out in a lethal and paroxystic gesture. Psychiatrists and psychologists may have an important part to play in modelling a pattern to better understand it. PMID- 27658989 TI - [Therapeutic benefit of a registered psychoeducation program on treatment adherence, objective and subjective quality of life: French pilot study for schizophrenia]. AB - INTRODUCTION: In schizophrenic disorders, supportive psychosocial therapies have been used as adjuncts to pharmacotherapy to help alleviate residual symptoms and to improve social functioning and quality of life. Among these therapies, psychoeducational therapies showed a significant efficacy on improving drug adherence and on reducing relapses. However, according to the French Health Agency, fewer than 10% of psychiatric structures in France offer registered psychoeducation programs. Caregiver apprehension of patients' depressive reactions to the awareness of the disease could underlie the underuse of psychoeducation therapies. Indeed, the psychoeducation programs' impact on objective and subjective quality of life is discussed among the literature. In this context, we conducted a retrospective, monocentric, open-labelled and non controlled pilot study to measure the impact of a registered psychoeducation program on objective and subjective quality of life of patients suffering from schizophrenia. Secondary objectives included measures of the effects on drug observance and awareness of the disease. METHODS: We included stabilized patients over the age of eighteen suffering from schizophrenia. Referent psychiatrics were asked to inform the patient of the diagnosis and to prescribe psychoeducation therapy. From 2011 to 2014, we offered three ambulatory programs, each program including fifteen two-hour group sessions. The groups were opened for three to six patients and managed by two caregivers. Themes discussed during the sessions included: schizophrenic disease, treatments, relationships to family, diet, social issues, toxics, relaxation. Objective and subjective quality of life were evaluated one month before and one month after the program using respectively the global assessment functioning (GAF) and the subjective quality of life (SQoL) scales. The Medical Adherence Rating Scale (MARS) and the French IQ8 scale evaluated respectively drug adherence and awareness of the disease. All patients gave their written consent for the study. Based on medical records and scales, we compared data before and after the program using the Wilcoxon test, adapted for small samples. RESULTS: Fourteen patients, with a mean age of 37.6 years, were included. All patients had a chronic antipsychotic treatment and four benefitted from a bitherapy with a mood stabilizer. The mean length of disease was 15.3 years, with a mean number of 3.4 hospitalizations before inclusion. The participation rate was nearly twelve sessions out of fifteen. Mean GAF score before the program was 48/100. After the program, mean GAF score was significantly increased to 54/100 (P=0.008). As to SQoL score, we found a significant difference of the sub item psychological well-being from 3.2/5 before the program to 3.8/5 after the program (P=0.03). Global SQoL score and other sub items (self-esteem, resilience, and physical well-being) showed a slight but not significant improvement. The sub items family relationships and sentimental life were diminished, non-significantly. Concerning the drug adherence, the mean MARS score was significantly increased from 6.1 to 6.4/8 (P=0.03). Comparison of the insight IQ8 scale showed a slight but non-significant increase. When asked to note the program, patients were globally very satisfied, with a mean rate of 8.6/10. Of fourteen patients, one needed to be hospitalized three years after program. DISCUSSION: This retrospective study on a small sample of patients suffering from schizophrenic disorder pointed out a significant improvement on drug adherence, objective quality of life and psychological well-being, after an eight-month registered program of psychoeducational therapy. These results are in line with a recent report from the Cochrane group who reported a significant raise of GAF associated with psychoeducational therapies. The literature data for subjective quality of life are more contradictory. Despite the small sample and evaluation means that need to be corrected in further studies, we reproduced the results described in the literature regarding the improvement on drug adherence. However, the stability of these effects should be checked in the medium and long term. CONCLUSION: Adjunctive psychoeducation therapy has a positive impact on reducing relapses in schizophrenia. In this study, we showed a significant benefit on drug adherence, objective quality of life and psychological well-being on a small sample of patients and provide arguments for the development of psychoeducation programs which are currently underrepresented in France. Our results encourage conducting a further prospective multicenter controlled study on a larger sample to clarify the benefit of psychoeducational therapy on objective and subjective quality of life in schizophrenia. PMID- 27658990 TI - [Clozapine: Latest FDA recommendations and our practice]. PMID- 27658991 TI - [Efficacy and tolerance of PDE-5 in the treatment of erectile dysfunction in schizophrenic patients: A literature review]. AB - INTRODUCTION: Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients. This literature review aimed to summarize the current data on the efficacy and tolerability of PDE-5 inhibitors in the erectile dysfunction in schizophrenic patients. MATERIAL AND METHODS: PubMed, PsycInfo and Cochrane databases were searched for studies published until August 2014. RESULTS: Only 6 studies met the inclusion criteria. Three were randomized, double-blind, cross-over, placebo controlled trials and three were open studies. Various scales were used to measure erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, quality of life and intensity of schizophrenic symptoms. In the 3 randomized studies (one with sildenafil 25-50 mg, one with lodenafil carbonate 80 mg/j and the last one with tadalafil 10 mg), the rate of participants who completed the trial was high (around 95 %). All three included patients with schizophrenia or schizophrenia spectrum disorders. Patients reported significant improvement on sexual dysfunction. However, no statistical difference was reported between lodenafil and placebo, on different scales, suggesting a very important placebo effect in patients with schizophrenia. All three found a good tolerance of PDE-5 inhibitors. Side effects were rare and were mainly nasal congestion, headaches, nausea and dizziness. There were no major side effects or drug interactions. Considering the 3 open studies, 2 involved sildenafil and one tadalafil. All concluded in improved erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. DISCUSSION: Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. CONCLUSION: In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia. PMID- 27658992 TI - CDC73 gene mutations in sporadic ossifying fibroma of the jaws. AB - BACKGROUND: The tumor suppressor gene CDC73 was found to be associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is characterized by parathyroid adenoma or carcinoma, ossifying fibroma (OF) of the jaws, and renal and uterine lesions. Mutations in CDC73 have also been frequently detected in sporadic parathyroid carcinomas and renal tumors. However, the prevalence and range of CDC73 mutations in sporadic OFs have not been established. METHODS: We directly sequenced coding and flanking splice junctional regions of CDC73 in 40 cases of sporadic OF of the jaws. We also used immunohistochemistry to detect parafibromin, the protein product of CDC73, in those cases. RESULTS: Two novel CDC73 mutations were identified in 2 of the 40 cases (5 %). Both were somatic mutations located in exon 1 of the coding region. Strong parafibromin expression was detected in all 40 cases, irrespective of the presence of CDC73 mutations. CONCLUSIONS: Mutations inCDC73 were rare in sporadic OF of the jaws, but may affect the pathogenesis of a small subset of tumors of this type. PMID- 27658993 TI - Biological Evaluation of Implant Drill Made from Zirconium Dioxide. AB - PURPOSE: Zirconia is a good candidate material in the dental field. In this study, we evaluated biological responses against a zirconia drill using a bone cavity healing model. MATERIALS AND METHODS: Zirconia drills, stainless steel drills, and the drilled bone surface were observed by scanning electron microscopy (SEM), before and after cavity preparation. For the bone cavity healing model, the upper first and second molars of Wistar rats were extracted. After 4 weeks, cavities were prepared with zirconia drills on the left side. As a control, a stainless steel drill was used on the right side. At 3, 7, and 14 days after surgery, micro-CT images were taken. Samples were prepared for histological staining. RESULTS: SEM images revealed that zirconia drills maintained sharpness even after 30 drilling procedures. The bone surface was smoother with the zirconia drill. Micro-CT images showed faster and earlier bone healing in the zirconia drill cavity. On H-E staining, at 7 days, the zirconia drill defect had a smaller blank lacunae area. At 14 days, the zirconia drill defect was filled with newly formed bone. CONCLUSIONS: The zirconia drill induces less damage during cavity preparation and is advantageous for bone healing. (197 words). PMID- 27658994 TI - A 3D-QSAR Study on Betulinic Acid Derivatives as Anti-Tumor Agents and the Synthesis of Novel Derivatives for Modeling Validation. AB - BACKGROUND: Betulinic acid is a lupane-type triterpene firstly extracted from the bark of white birch. It has displayed anti-inflammatory, antioxidant, anti-HIV and selective cytotoxicity. OBJECTIVE: To understand the structure- anti-tumor activity relationship of betulinic acid and betulin derivatives and to synthesize novel anti-tumor derivatives of betulinic acid and betulin. METHOD: The 3D-QSAR methods including CoMFA and CoMSIA methods were performed to study the structureanti- tumor activity relationship of betulinic acid (BA) and betulin (BE) derivatives. RESULTS: According to the models, near the C-3 site, non-bulky, negatively charged electron-donating, hydrophobic, non-hydrogen-bond-donating and hydrogen-bond-accepting groups are favored to the activity. Around the C-28 site, the bulky, positively charged electron-withdrawing and hydrophobic groups are favored, whereas hydrophilic groups may be introduced at the terminal of the side chain. Based on the models, BA and BE were esterified with substituted amino acid derivatives achieving novel derivatives for the modeling validation. CONCLUSION: The experimental results verified the modeling rules, and showed when different rules may apply to the new structures, the steric effects might be more important. The synthesized derivatives were showed promising cytotoxicity against tested cancer cell lines. PMID- 27658995 TI - The effects of mindfulness training on weight-loss and health-related behaviours in adults with overweight and obesity: A systematic review and meta-analysis. AB - The aim of this study was to conduct a comprehensive quantitative synthesis of the effects of mindfulness training interventions on weight-loss and health behaviours in adults with overweight and obesity using meta-analytic techniques. Studies included in the analysis (k=12) were randomised controlled trials investigating the effects of any form of mindfulness training on weight loss, impulsive eating, binge eating, or physical activity participation in adults with overweight and obesity. Random effects meta-analysis revealed that mindfulness training had no significant effect on weight loss, but an overall negative effect on impulsive eating (d=-1.13) and binge eating (d=-.90), and a positive effect on physical activity levels (d=.42). Meta-regression analysis showed that methodological features of included studies accounted for 100% of statistical heterogeneity of the effects of mindfulness training on weight loss (R2=1,00). Among methodological features, the only significant predictor of weight loss was follow-up distance from post-intervention (beta=1.18; p<.05), suggesting that the longer follow-up distances were associated with greater weight loss. Results suggest that mindfulness training has short-term benefits on health-related behaviours. Future studies should explore the effectiveness of mindfulness training on long-term post-intervention weight loss in adults with overweight and obesity. PMID- 27658996 TI - Oxytocin, a main breastfeeding hormone, prevents hypertension acquired in utero: A therapeutics preview. AB - Hypertension is a major risk factor for ischemic heart disease and stroke, leading causes of morbidity and death worldwide. Intrauterine growth restriction (IUGR), caused by an excess of glucocorticoid exposure to the fetus, produces an imbalance in oxidative stress altering many biochemical and epigenetic gene transcription processes exposing the fetus and neonate to the 'thrifty' phenotype and pervasive polymorphisms appearance damaging health, cognitive, and behavioral processes in later life. OT is a major regulator of oxidative stress radicals that plays a major role in neonatal maturation of the central nervous system and many peripheral tissues expressing oxytocin/oxytocin-receptor (OT/OTR) system in the early postnatal period. OT and OTR are damaged by IUGR and early stress. This review highlights the fact that hypertension is likely to be a legacy of preterm birth due to IUGR and failure to meet nutritional needs in early infancy when fed formula instead of breastfeeding or human milk. PMID- 27658997 TI - Controlling intraoperative hemorrhage during burn surgery: A prospective, randomized trial comparing NuStat(r) hemostatic dressing to the historic standard of care. AB - INTRODUCTION: One of the primary intraoperative challenges during burn surgery is to adequately excise the burn while avoiding massive hemorrhage. This has become increasingly important, as we see more burn patients that are older and with more medical comorbidities. While adequate excision down to healthy tissues for deep burns is essential for skin graft to take, it also leads to active bleeding that can be a challenge to control. Good hemostasis is imperative as a hematoma is the most common cause of graft loss. Several new products have become available to help control intraoperative hemorrhage. A new hemostatic dressing, NuStat(r), is available and approved by FDA in United States. METHODS: A single institution prospective randomized control trial was completed at Regional Burn Center of the University of South Alabama comparing NuStat(r) with the institutional historic standard of care. Twenty such patients were included in our study. A cost analysis was also completed as part of the study retrospectively. RESULTS: For dressings used to treat the burn site, blood loss on the side treated with NuStat(r) was on average less (27g/100cm2) than the side treated with our historic standard of care (31g/100cm2), though it was not statistically significant (p=0.81). Similarly, on the donor site, blood loss on the side treated with NuStat(r) was on average less (14g/100cm2) than the side treated with our historic standard of care (15g/100cm2), but it was also not statistically significant (p=0.92). Average total blood loss from both excision and donor sites was also less with NuStat(r) (10g/100cm2) compared to the historic standard of care (12g/100cm2), but it was also not significant (p=0.77). There was no difference in the number of cycles required to achieve hemostasis for either the burn (1.15 NuStat(r) vs. 1.1 for historic standard of care, p=0.70) or the donor site (1 vs. 1, p=1.0). When comparing the cost of NuStat(r) versus the historic standard of care, the actual costs incurred for the wounds was less for the portion treated with NuStat(r) ($148.43) when compared to the historic standard of care ($186.45) (p<0.001). CONCLUSIONS: Based on these findings, NuStat(r) hemostatic action should be comparable to the historic standard of care, and these newer hemostatic agents evaluated further in burn surgery and bleeding during other procedures such as trauma surgery. PMID- 27658998 TI - The impact of patient demographics and comorbidities upon burns admitted to Tygerberg Hospital Burns Unit, Western Cape, South Africa. AB - In South Africa, burns are a major public health problem responsible for significant morbidity and long-term physical disability. This is, in part, due to a significant proportion of the urban population living in poorly constructed, combustible accommodation. The presence of co-morbid diseases such as diabetes and malignancy in patients with burns has been associated with a poorer outcome. The impact of other diseases such as HIV has yet to be defined. A retrospective data collection study analysed the 221 patients admitted to Tygerberg Hospital Burns Unit in 2011 and the first six months of 2013. Using hospital records, patient demographic data was collected alongside burn agent, ICU admission, complications, and patient outcome in terms of length of stay and mortality. The most common burn agent was hot liquid (45.7%). A significant proportion of patients were subject to intentional attacks (34.3%). Shack fires and flame accounted cumulatively for 85% of total inhalational burns, the highest rates of admission to ICU (85.5%), the highest rate of complications, as well as 92.3% of all total fatalities. HIV+ patients had a higher mortality (13.3% vs 5%, p=0.22) and a higher complication rate (46.7% vs 30%, p=0.21). There was no difference in length of stay between the HIV+ and HIV- cohort (12days vs. 15.5 days, p=0.916). Burns are a significant yet preventable cause of mortality and morbidity. The rising number of shack fires, responsible for extensive burns and resultant mortality is concerning and indicates urgent attention and action. HIV complicates the recovery from burn and is responsible for an increased rate of in hospital mortality. PMID- 27658999 TI - Association between prefrontal N-acetylaspartate and insight in psychotic disorders. AB - Insight is impaired in most patients with psychosis and has been associated with poorer prognosis. The exact neural basis of impaired insight is still unknown, but it may involve disrupted prefrontal neural connectivity. Numerous studies have indeed found white matter (WM) abnormalities in psychosis. The association between prefrontal WM abnormalities and insight has not been studied yet by means of proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS can be used to measure N-acetylaspartate (NAA), which is considered to be a marker of neuronal integrity. We measured insight with the Birchwood Insight Scale (BIS) as well as item G12 of the Positive and Negative Syndrome Scale (PANSS) in 88 patients with psychosis. Prefrontal WM concentrations of NAA and ratios of NAA to creatine (Cr) were assessed with 1H-MRS. Nonparametric partial correlational analyses were conducted between NAA concentrations and insight controlling for illness duration, standardized antipsychotic dose, symptom scores, voxel grey matter content and voxel cerebrospinal fluid content. We found a significant correlation between reduced NAA/Cr ratios and poorer insight as measured with the BIS, which remained significant after additional correction for full width at half maximum, signal/noise and age. This is the first study reporting a relationship between lower prefrontal concentrations of a marker of neuronal integrity and impaired insight, providing further evidence that prefrontal pathology may play an important role in impaired insight in psychosis. This may be explained by the involvement of the prefrontal cortex in several executive and metacognitive functions, such as cognitive flexibility and perspective taking. PMID- 27659000 TI - Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres. AB - OBJECTIVE: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. METHODS AND MATERIALS: Five hundred sixty five patients with LRRC who underwent multimodality treatment up to 2010 were studied. The preferred treatment was preoperative chemo radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. RESULTS: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full course treatment, except the chance of local re-recurrence was higher for re irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection. CONCLUSIONS: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence. PMID- 27659001 TI - Comparison of immunoregulatory effects of polysaccharides from three natural herbs and cellular uptake in dendritic cells. AB - Polysaccharides from different types of natural herbs have not been compared with each other to determine their differential potencies on innate immune response, such as maturation of dendritic cells (DC). In addition, the role of endocytosis of polysaccharides in DC maturation has not been explored previously. Polysaccharides isolated from Astragalus membranaceus (APS), Ganoderma lucidum (GLP) and Radix ophiopogonis (OGP) were characterized and applied in bone marrow derived DC. Compared to immature DC, three polysaccharides with immunoactivities showed elongated dendrites, decreased phagocytic abilities, phenotypic changes (CD40/MHCII/CD80/CD86) and increased level of nitric oxide (NO) in a dose dependent manner. Interestingly, blockage of NO by iNOS inhibitor slightly decreased CD40 and MHCII but not CD80/CD86 expression induced by polysaccharides, indicating that NO was partially involved in DC maturation. In addition, GLP can enter cells in a dose and time dependent manner, shown as punctate distribution in the cytoplasm. Endocytic inhibitors sodium azide and brefeldinA that were demonstrated to inhibit cellular uptake of GLP can block phenotypic maturation of DC. Taken together, these results suggested that polysaccharides from natural herbs are effective immunostimulators with variable potencies ranking as GLP>APS>OGP, and the increase of NO level as well as the increase in polysaccharide endocytosis could be the novel strategies for improved innate response and immunotherapy. PMID- 27659002 TI - Insight into the phylogenetic relationship and structural features of vertebrate myoglobin family. AB - Myoglobin (Mb) is studied to clarify the structure-function relationships in protein science. In this work, we report the results of a comparative analysis of amino acid sequences from 298 vertebrate Mbs. Forty-one high conserved residues were identified and seven of them were invariants [E18, G25, F43, V68, L72, H93 (proximal histidine) and H97]. E18 is the only invariant amino acid residue located out of the heme-pocket and Xe-cavities playing a role in interaction between the A and E-helices. A comparative analysis of several parameters related to amino acid composition shows an increase of average mass, accessible surface area and volume per residue from Actinopterygii to Mammalia and Aves. This may be due to an increased number of bulky residues reducing the non-specific cavities volume and thus improving the oxygen flow between the heme site and the outside of the protein. Finally, the phylogenetic analyses of Mb in vertebrates are consistent with an evolution that runs with the diversification of the species, but in which several episodes of gene duplication and lost have occurred, less frequently in the ancestors of great taxons, cartilaginous fishes and non-avian reptiles, most frequently in ray-finned fishes and mammals, and very frequently in birds. PMID- 27659003 TI - Ketoconazole encapsulated in chitosan-gellan gum nanocomplexes exhibits prolonged antifungal activity. AB - The objective of the present study was to prepare ketoconazole loaded chitosan gellan gum (CSGG) nanoparticles and to evaluate them for antifungal activity against Aspergillus niger. Ketoconazole loaded CSGG nanoparticles were prepared by electrostatic complexation technique using chitosan (CS) as cationic polymer and gellan gum (GG) as anionic polymer with ketoconazole as drug. It was observed that the effect of gellan gum on particle size was more pronounced in comparison to chitosan and increase in its concentration resulted in a significant increase in particle size but decrease in zeta potential. Whereas, increase in concentration of chitosan resulted in increase in zeta potential. The particle size and zeta potential of optimal formulation was 155.7+/-26.1nm and 32.1+/ 2.8mV which obtained at concentration of chitosan (0.02% w/v) and gellan gum (0.01% w/v). On comparative evaluation, ketoconazole loaded CSGG nanoparticles showed significantly higher antifungal activity against Aspergillus niger than dummy CSGG nanoparticles (without drug) and drug individually. PMID- 27659004 TI - Well-Being and Self-Assessment of Change: Secondary Analysis of an RCT That Demonstrated Benefit of Inhaled Lavender and Sleep Hygiene in College Students with Sleep Problems. AB - CONTEXT: Sleep issues are prevalent and affect health and well-being. The aspects of well-being that are impacted by sleep interventions have not been well studied. OBJECTIVES: To investigate the impact of lavender and sleep hygiene (LSH) compared to sleep hygiene (SH) alone on well-being as measured by the Self assessment of Change questionnaire (SAC) at post-intervention and two-week follow up, and secondarily to compare the SAC sleep item to results from standardized sleep surveys. DESIGN: Secondary analysis of a randomized controlled trial (RCT) where one group received a lavender inhalation patch and practiced sleep hygiene (LSH) and the other group received a placebo inhalation patch and practiced sleep hygiene (SH) for five consecutive nights. SETTING: Usual sleep setting. PARTICIPANTS: Seventy-nine college students with self-reported sleep issues. MAIN OUTCOME MEASURES: The SAC was completed at post-intervention and follow-up. RESULTS: Exploratory analysis showed significantly improved well-being for the LSH group at post-intervention for well-being domains of sleep, energy, and vibrancy (P = .01, .03, and .05, respectively) and an overall trend of improved well-being in comparison to the SH group at post-intervention and follow-up. The SAC sleep item showed a similar pattern of change to the standardized sleep surveys with a statistically significant improvement in sleep for the LSH group at follow-up (P = .02). CONCLUSIONS: Findings demonstrate the positive impact of the lavender intervention on three domains of self-assessed well-being are energy, vibrancy, and sleep. SAC results extend and complement prior findings of improved sleep quality. PMID- 27659005 TI - Rescue of Moribund Chicken Embryos by Extremely Low-Frequency Electric Fields. AB - BACKGROUND: Modern living is awash with low-frequency electromagnetic radiation raising concern over health effects, birth defects, and infant cancers especially leukemias. Medical/scientific opinion is ambivalent, especially regarding possible mechanisms of action despite our bodies' many electric currents. AIMS: Are some cancers induced by morphogenetic changes rather than direct mutation? We wished to see if morphogenetic effects of weak, extremely low-frequency electric (ELF) fields in embryonated hen's eggs could induce cancers, knowing that such treatment is usually deleterious. We report a pilot study intended to reveal a promising cell source in which to search for cancer cells by established methods and then to check for DNA damage. METHODS: Stored (5 degrees C for 1-36 days) fresh, fertile hens' eggs were incubated (38 degrees C, total five or six days) in presence or absence of a weak ELF oscillating electric field (1-40V/cm, 1-50Hz and two to six days). Separated embryos were assessed for development stage. RESULTS: Storage of untreated eggs (>12 days, 5 degrees C) allows a steady loss of normal embryo formation at 38 degrees C (few viable by 25 days, half-life ~18 days). Surprisingly, incubation in a weak ELF field during the period of declining viability significantly (P: 0.03-0.0001) improved viability and condition of the embryos (new half-life ~21 days), rather than the expected converse. Thus for a few days, the field could keep viable some embryos that would otherwise not have survived. CONCLUSIONS: The rescued embryos and their untreated controls seem the most promising place to seek any carcinogenic effects of ELF fields. The nature of the presumed critical component keeping them viable during 5 degrees C storage is at least of equal interest. PMID- 27659006 TI - Influence of voxel S factors on three-dimensional internal dosimetry calculations. AB - Internal dosimetry is a fundamental instrument for the personalization of nuclear medicine therapies, to maximize the therapeutic effect while minimizing the radiation burden to other organs. Three-dimensional (3D) dosimetry can quantify the impact of heterogeneous radiopharmaceutical distributions in organs, lesions and tissues. We analysed the influence of radionuclide voxel S factors in 3D dosimetry of 111In, 177Lu and 90Y, the most used radionuclides in Peptide Receptor Radionuclide Therapy (PRRT). Calculations were carried out for kidneys on a workstation equipped with a software for 3D dosimetry (Imalytics STRATOS, Philips AG), adopting a computational anthropomorphic phantom and, retrospectively, the SPECT-CT image series of a clinical case of PRRT. Two sets of voxel S factors were adopted: the pre-loaded Philips kernels, calculated by direct Monte Carlo simulation, and the ones calculated through a previously proposed analytical approach. Philips 111In kernel did not account for mono energetic Auger or Conversion electrons. Results indicate a difference of about 32% in voxel S factors for 111In in 4.42mm voxel size and around -35% in 4.80mm voxel size, particularly self-dose values; this lead to significant shift in dose histograms and average doses. For 177Lu and 90Y, differences are about 2% and 12% for 4.42mm voxels and about -8% and 9% for 4.80mm voxels, respectively, attributable to the different calculation methods of the voxel S factors; this does not lead to significant discrepancies between the two dose histograms. Consequently, voxel S factors must account accurately for all radiations emitted by the nuclide. PMID- 27659007 TI - Review of Geant4-DNA applications for micro and nanoscale simulations. AB - Emerging radiotherapy treatments including targeted particle therapy, hadron therapy or radiosensitisation of cells by high-Z nanoparticles demand the theoretical determination of radiation track structure at the nanoscale. This is essential in order to evaluate radiation damage at the cellular and DNA level. Since 2007, Geant4 offers physics models to describe particle interactions in liquid water at the nanometre level through the Geant4-DNA Package. This package currently provides a complete set of models describing the event-by-event electromagnetic interactions of particles with liquid water, as well as developments for the modelling of water radiolysis. Since its release, Geant4-DNA has been adopted as an investigational tool in kV and MV external beam radiotherapy, hadron therapies using protons and heavy ions, targeted therapies and radiobiology studies. It has been benchmarked with respect to other track structure Monte Carlo codes and, where available, against reference experimental measurements. While Geant4-DNA physics models and radiolysis modelling functionalities have already been described in detail in the literature, this review paper summarises and discusses a selection of representative papers with the aim of providing an overview of a) geometrical descriptions of biological targets down to the DNA size, and b) the full spectrum of current micro- and nano scale applications of Geant4-DNA. PMID- 27659008 TI - Clinical implementation of a Monte Carlo based treatment plan QA platform for validation of Cyberknife and Tomotherapy treatments. AB - PURPOSE: The main focus of the current paper is the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, without adding additional tasks to the dosimetry department. METHODS: The Monte Carlo platform consists of C++ classes for the actual functionality and a web based GUI that allows accessing the system using a web browser. Calculations are based on BEAMnrc/DOSXYZnrc and/or GATE and are performed automatically after exporting the dicom data from the treatment planning system. For Cyberknife treatments of moving targets, the log files saved during the treatment (position of robot, internal fiducials and external markers) can be used in combination with the 4D planning CT to reconstruct the actually delivered dose. The Monte Carlo platform is also used for calculation on MRI images, using pseudo-CT conversion. RESULTS: For Tomotherapy treatments we obtain an excellent agreement (within 2%) for almost all cases. However, we have been able to detect a problem regarding the CT Hounsfield units definition of the Toshiba Large Bore CT when using a large reconstruction diameter. For Cyberknife treatments we obtain an excellent agreement with the Monte Carlo algorithm of the treatment planning system. For some extreme cases, when treating small lung lesions in low density lung tissue, small differences are obtained due to the different cut-off energy of the secondary electrons. CONCLUSIONS: A Monte Carlo based treatment plan validation tool has successfully been implemented in clinical routine and is used to systematically validate all Cyberknife and Tomotherapy plans. PMID- 27659009 TI - Chromate and amine contact allergies in workers manufacturing precast concrete elements. AB - BACKGROUND: Five workers from a plant manufacturing concrete wall panels and beams were referred to our department because of suspected occupational dermatitis. When patch tested, 3 workers reacted to potassium dichromate. Four workers reacted to ethylenediamine dihydrochloride, without any obvious exposure. Owing to the high proportion of workers with recent-onset skin disease, an investigation of all workers at the plant was initiated. OBJECTIVES: To investigate the prevalence of occupational dermatitis and contact allergy in the workers at the plant. METHODS: All 24 workers at the plant underwent a clinical investigation and were patch tested. RESULTS: Four cases of allergic occupational contact dermatitis and 3 cases of irritant occupational contact dermatitis were diagnosed. Contact allergy to potassium dichromate was found in 4 workers. All 4 also reacted to ethylenediamine dihydrochloride and/or amines that were present as additives in the cement. CONCLUSIONS: Chromate contact allergy can still be found in concrete workers, despite the legislation regulating the amount of hexavalent chromium (chromate) in cement. Occupational contact allergy to amines can be found in workers exposed to cement and concrete, so amines should be tested in these workers. PMID- 27659011 TI - PathCellNet: Cell-type specific pathogen-response network explorer. AB - Pathogen specific immune response is a complex interplay between several innate and adaptive immune cell-types. Innate immune cells play a critical role in pathogen recognition and initiating the antigen specific adaptive immune response. Despite specific functional roles of the innate immune cells, they share several anti-viral pathways. The question then becomes, what is the overlap in the transcriptional changes induced upon viral infections across different cell-types? Here we investigate the extent to which gene signatures are conserved across innate immune cell-types by performing a comparative analysis of transcriptomic data. Particularly, we integrate transcriptomic datasets measuring response of two innate immune cells (epithelial and dendritic cells) to influenza virus. The study reveals cell-type specific regulatory genes and a conserved network between the two cell-types. Additionally, novel functionally associated gene clusters are identified which are robustly defined across multiple independent studies. These gene clusters can be used in future investigation, and to facilitate their use we release PathCellNet (version 0), a cloud based tool to explore cell-type specific connectivity of user-defined genes. In the future, expansion of PathCellNet will allow exploration of cell-type specific responses across a variety of pathogens and cell-types. PMID- 27659010 TI - Detection of herpes simplex virus type 2 (HSV-2) -specific cell-mediated immune responses in guinea pigs during latent HSV-2 genital infection. AB - Genital infections with herpes simplex virus type 2 (HSV-2) are a source of considerable morbidity and are a health concern for newborns exposed to virus during vaginal delivery. Additionally, HSV-2 infection diminishes the integrity of the vaginal epithelium resulting in increased susceptibility of individuals to infection with other sexually transmitted pathogens. Understanding immune protection against HSV-2 primary infection and immune modulation of virus shedding events following reactivation of the virus from latency is important for the development of effective prophylactic and therapeutic vaccines. Although the murine model of HSV-2 infection is useful for understanding immunity following immunization, it is limited by the lack of spontaneous reactivation of HSV-2 from latency. Genital infection of guinea pigs with HSV-2 accurately models the disease of humans including the spontaneous reactivation of HSV-2 from latency and provides a unique opportunity to examine virus-host interactions during latency. Although the guinea pig represents an accurate model of many human infections, relatively few reagents are available to study the immunological response to infection. To analyze the cell-mediated immune response of guinea pigs at extended periods of time after establishment of HSV-2 latency, we have modified flow-cytometry based proliferation assays and IFN-gamma ELISPOT assays to detect and quantify HSV-specific cell-mediated responses during latent infection of guinea pigs. Here we demonstrate that a combination of proliferation and ELISPOT assays can be used to quantify and characterize effecter function of virus-specific immune memory responses during HSV-latency. PMID- 27659012 TI - Induction of Activating Transcription Factor 3 Is Associated with Cisplatin Responsiveness in Non-Small Cell Lung Carcinoma Cells. AB - Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer deaths, with platin-based combination chemotherapy the most efficacious therapies. Gains in overall survival are modest, highlighting the need for novel therapeutic approaches including the development of next-generation platin combination regimens. The goal of this study was to identify novel regulators of platin induced cytotoxicity as potential therapeutic targets to further enhance platin cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their cisplatin-resistant sublines, Calu6cisR1 and H23cisR1, activating transcription factor 3 (ATF3) was robustly induced in cisplatin-treated parental sensitive cell lines but not their resistant sublines, and in three of six tumors evaluated, but not in their corresponding normal adjacent lung tissue (0/6). Cisplatin-induced JNK activation was a key regulator of this ATF3 induction. Interestingly, in both resistant sublines, this JNK induction was abrogated, and the expression of an activated JNK construct in these cells enhanced both cisplatin-induced cytotoxicity and ATF3 induction. An FDA-approved drug compound screen was employed to identify enhancers of cisplatin cytotoxicity that were dependent on ATF3 gene expression. Vorinostat, a histone deacetylase inhibitor, was identified in this screen and demonstrated synergistic cytotoxicity with cisplatin in both the parental Calu6 and H23 cell lines and importantly in their resistant sublines as well that was dependent on ATF3 expression. Thus, we have identified ATF3 as an important regulator of cisplatin cytotoxicity and that ATF3 inducers in combination with platins are a potential novel therapeutic approach for NSCLC. PMID- 27659013 TI - Frontline Dasatinib Treatment in a "Real-Life" Cohort of Patients Older than 65 Years with Chronic Myeloid Leukemia. AB - Dasatinib (DAS) has been licensed for the frontline treatment in chronic myeloid leukemia (CML). However, very few data are available regarding its efficacy and toxicity in elderly patients with CML outside clinical trials. To address this issue, we set out a "real-life" cohort of 65 chronic phase CML patients older than 65 years (median age 75.1 years) treated frontline with DAS in 26 Italian centers from June 2012 to June 2015, focusing our attention on toxicity and efficacy data. One third of patients (20/65: 30.7%) had 3 or more comorbidities and required concomitant therapies; according to Sokal classification, 3 patients (4.6%) were low risk, 39 (60.0%) intermediate risk, and 20 (30.8%) high risk, whereas 3 (4.6%) were not classifiable. DAS starting dose was 100 mg once a day in 54 patients (83.0%), whereas 11 patients (17.0%) received less than 100 mg/day. Grade 3/4 hematologic and extrahematologic toxicities were reported in 8 (12.3%) and 12 (18.5%) patients, respectively. Overall, 10 patients (15.4%) permanently discontinued DAS because of toxicities. Pleural effusions (all WHO grades) occurred in 12 patients (18.5%) and in 5 of them occurred during the first 3 months. DAS treatment induced in 60/65 patients (92.3%) a complete cytogenetic response and in 50/65 (76.9%) also a major molecular response. These findings show that DAS might play an important role in the frontline treatment of CML patients >65 years old, proving efficacy and having a favorable safety profile also in elderly subjects with comorbidities. PMID- 27659015 TI - DNMT1 Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cells, Which Promotes Prostate Cancer Metastasis. AB - Cancer metastasis is a multistep process associated with the induction of an epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Although significant progress has been made in understanding the molecular mechanisms regulating EMT and the CSC phenotype, little is known of how these processes are regulated by epigenetics. Here we demonstrate that reduced expression of DNA methyltransferase 1 (DNMT1) plays an important role in the induction of EMT and the CSC phenotype by prostate cancer (PCa) cells, with enhanced tumorigenesis and metastasis. First, we observed that reduction of DNMT1 by 5-azacitidine (5-Aza) promotes EMT induction as well as CSCs and sphere formation in vitro. Reduced expression of DNMT1 significantly increased PCa migratory potential. We showed that the increase of EMT and CSC activities by reduction of DNMT1 is associated with the increase of protein kinase C. Furthermore, we confirmed that silencing DNMT1 is correlated with enhancement of the induction of EMT and the CSC phenotype in PCa cells. Additionally, chromatin immunoprecipitation assay reveals that reduction of DNMT1 promotes the suppression of H3K9me3 and H3K27me3 on the Zeb2 and KLF4 promoter region in PCa cells. Critically, we found in an animal model that significant tumor growth and more disseminated tumor cells in most osseous tissues were observed following injection of 5-Aza pretreated-PCa cells compared with vehicle-pretreated PCa cells. Our results suggest that epigenetic alteration of histone demethylation regulated by reduction of DNMT1 may control induction of EMT and the CSC phenotype, which facilitates tumorigenesis in PCa cells and has important therapeutic implications in targeting epigenetic regulation. PMID- 27659018 TI - Hospitalization Among HIV-Infected U.S. Marshals Service Prisoners. AB - The U.S. Marshals Service (USMS) prisoner population is diverse and includes immigration violators, fugitives that have evaded apprehension, perpetrators of Medicaid fraud, and parole and probation violators. Unlike state and local jails, the USMS has numerous housing options for its prisoners. Given the unique characteristics, federal prisoners' quality of care, and subsequent clinical outcomes, may differ from those of state and local inmates. However, little is known about hospitalization rates and length of stay for HIV-positive USMS prisoners. The purpose of this study is to examine hospitalizations among HIV infected prisoners in the custody of the USMS. PMID- 27659017 TI - Clinical Genotyping of Non-Small Cell Lung Cancers Using Targeted Next-Generation Sequencing: Utility of Identifying Rare and Co-mutations in Oncogenic Driver Genes. AB - Detection of somatic mutations in non-small cell lung cancers (NSCLCs), especially adenocarcinomas, is important for directing patient care when targeted therapy is available. Here, we present our experience with genotyping NSCLC using the Ion Torrent Personal Genome Machine (PGM) and the AmpliSeq Cancer Hotspot Panel v2. We tested 453 NSCLC samples from 407 individual patients using the 50 gene AmpliSeq Cancer Hotspot Panel v2 from May 2013 to July 2015. Using 10 ng of DNA, up to 11 samples were simultaneously sequenced on the Ion Torrent PGM (316 and 318 chips). We identified variants with the Ion Torrent Variant Caller Plugin, and Golden Helix's SVS software was used for annotation and prediction of the significance of the variants. Three hundred ninety-eight samples were successfully sequenced (12.1% failure rate). In all, 633 variants in 41 genes were detected with a median of 2 (range of 0 to 7) variants per sample. Mutations detected in BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA were considered potentially actionable and were identified in 237 samples, most commonly in KRAS (37.9%), EGFR (11.1%), BRAF (4.8%), and PIK3CA (4.3%). In our patient population, all mutations in EGFR, KRAS, and BRAF were mutually exclusive. The Ion Torrent Ampliseq technology can be utilized on small biopsy and cytology specimens, requires very little input DNA, and can be applied in clinical laboratories for genotyping of NSCLC. This targeted next-generation sequencing approach allows for detection of common and also rare mutations that are clinically actionable in multiple patients simultaneously. PMID- 27659014 TI - Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia. AB - Preclinical studies have suggested that the pancreatic tumor microenvironment both inhibits and promotes tumor development and growth. Here we establish the role of stromal fibroblasts during acinar-to-ductal metaplasia (ADM), an initiating event in pancreatic cancer formation. The transcription factor V-Ets avian erythroblastosis virus E26 oncogene homolog 2 (ETS2) was elevated in smooth muscle actin-positive fibroblasts in the stroma of pancreatic ductal adenocarcinoma (PDAC) patient tissue samples relative to normal pancreatic controls. LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) mice showed that ETS2 expression initially increased in fibroblasts during ADM and remained elevated through progression to PDAC. Conditional ablation of Ets-2 in pancreatic fibroblasts in a Kras(G12D)-driven mouse ADM model decreased the amount of ADM events. ADMs from fibroblast Ets-2-deleted animals had reduced epithelial cell proliferation and increased apoptosis. Surprisingly, fibroblast Ets-2 deletion significantly altered immune cell infiltration into the stroma, with an increased CD8+ T-cell population, and decreased presence of regulatory T cells (Tregs), myeloid-derived suppressor cells, and mature macrophages. The mechanism involved ETS2-dependent chemokine ligand production in fibroblasts. ETS2 directly bound to regulatory sequences for Ccl3, Ccl4, Cxcl4, Cxcl5, and Cxcl10, a group of chemokines that act as potent mediators of immune cell recruitment. These results suggest an unappreciated role for ETS2 in fibroblasts in establishing an immune suppressive microenvironment in response to oncogenic Kras(G12D) signaling during the initial stages of tumor development. PMID- 27659016 TI - Hypoxia-Inducible Factor 2alpha Mutation-Related Paragangliomas Classify as Discrete Pseudohypoxic Subcluster. AB - Recently, activating mutations of the hypoxia-inducible factor 2alpha gene (HIF2A/EPAS1) have been recognized to predispose to multiple paragangliomas (PGLs) and duodenal somatostatinomas associated with polycythemia, and ocular abnormalities. Previously, mutations in the SDHA/B/C/D, SDHAF2, VHL, FH, PHD1, and PHD2 genes have been associated with HIF activation and the development of pseudohypoxic (cluster-1) PGLs. These tumors overlap in terms of tumor location, syndromic presentation, and noradrenergic phenotype to a certain extent. However, they also differ especially by clinical outcome and by presence of other tumors or abnormalities. In the present study, we aimed to establish additional molecular differences between HIF2A and non-HIF2A pseudohypoxic PGLs. RNA expression patterns of HIF2A PGLs (n=6) from 2 patients were compared with normal adrenal medullas (n=8) and other hereditary pseudohypoxic PGLs (VHL: n=13, SDHB: n=15, and SDHD: n=14). Unsupervised hierarchical clustering showed that HIF2A PGLs made up a separate cluster from other pseudohypoxic PGLs. Significance analysis of microarray yielded 875 differentially expressed genes between HIF2A and other pseudohypoxic PGLs after normalization to adrenal medulla (false discovery rate 0.01). Prediction analysis of microarray allowed correct classification of all HIF2A samples based on as little as three genes (TRHDE, LRRC63, IGSF10; error rate: 0.02). Genes with the highest expression difference between normal medulla and HIF2A PGLs were selected for confirmatory quantitative reverse transcriptase polymerase chain reaction. In conclusion, HIF2A PGLs show a characteristic expression signature that separates them from non-HIF2A pseudohypoxic PGLs. Unexpectedly, the most significantly differentially expressed genes have not been previously described as HIF target genes. PMID- 27659020 TI - Influence of change in surgical practice for benign thyroid disease on postsurgical outcome-Single-center experience in 1400 patients. AB - PURPOSE: To evaluate the rate of surgical complications during the change from subtotal resection to hemithyroidectomy or thyroidectomy over a period of 17 years. METHODS: All operations for benign goiter at our hospital were analyzed for the periods 1996-2002 (Group 1) and 2003-2012 (Group 2). The groups were compared for recurrent laryngeal nerve damage, hypocalcemia, and other surgical complications directly postoperatively. RESULTS: In total, 1462 patients were operated on for goiter between 1996 and 2012. There were 1219 patients who underwent a primary thyroid operation, whereas 50 patients had surgery for recurrence. Postoperative histology revealed thyroid cancer in 193 patients (13.2%). In Group 1, 42.7% of all operated lobes were performed as lobectomies and 57.3% as subtotal resections; in Group 2, 74.4% were performed as lobectomies and 25.6% as subtotal resections. No differences were found for reduced vocal cord function (2.4% vs. 1.9%, p = 0.746) and recurrent laryngeal nerve paralysis in the postoperative laryngoscopy (2.9% vs. 1.8%, p = 0.675). Postoperative hypoparathyroidism was detected in 13.66% in Group 1 and in 19.80% in Group 2 after bilateral resections (p = 0.037). There was no difference in the rate of reoperations for cancer between both groups (43.4% vs. 52.1%, p = 0.182). CONCLUSION: Surgical practice changed from subtotal to lobectomies for benign goiter over a period of 17 years without change in laryngeal nerve damage but with increasing rates of postoperative hypocalcemia. PMID- 27659021 TI - Abstracts of the 11th Scientific and Annual Meeting of the European Society of Coloproctology, 28-30 September 2016, Milan, Italy. PMID- 27659019 TI - What Touched Your Heart? Collaborative Story Analysis Emerging From an Apsaalooke Cultural Context. AB - Community-based participatory research and decolonizing research share some recommendations for best practices for conducting research. One commonality is partnering on all stages of research; co-developing methods of data analysis is one stage with a deficit of partnering examples. We present a novel community based and developed method for analyzing qualitative data within an Indigenous health study and explain incompatibilities of existing methods for our purposes and community needs. We describe how we explored available literature, received counsel from community Elders and experts in the field, and collaboratively developed a data analysis method consonant with community values. The method of analysis, in which interview/story remained intact, team members received story, made meaning through discussion, and generated a conceptual framework to inform intervention development, is detailed. We offer the development process and method as an example for researchers working with communities who want to keep stories intact during qualitative data analysis. PMID- 27659024 TI - Do Branch Lengths Help to Locate a Tree in a Phylogenetic Network? AB - Phylogenetic networks are increasingly used in evolutionary biology to represent the history of species that have undergone reticulate events such as horizontal gene transfer, hybrid speciation and recombination. One of the most fundamental questions that arise in this context is whether the evolution of a gene with one copy in all species can be explained by a given network. In mathematical terms, this is often translated in the following way: is a given phylogenetic tree contained in a given phylogenetic network? Recently this tree containment problem has been widely investigated from a computational perspective, but most studies have only focused on the topology of the phylogenies, ignoring a piece of information that, in the case of phylogenetic trees, is routinely inferred by evolutionary analyses: branch lengths. These measure the amount of change (e.g., nucleotide substitutions) that has occurred along each branch of the phylogeny. Here, we study a number of versions of the tree containment problem that explicitly account for branch lengths. We show that, although length information has the potential to locate more precisely a tree within a network, the problem is computationally hard in its most general form. On a positive note, for a number of special cases of biological relevance, we provide algorithms that solve this problem efficiently. This includes the case of networks of limited complexity, for which it is possible to recover, among the trees contained by the network with the same topology as the input tree, the closest one in terms of branch lengths. PMID- 27659022 TI - Quality of life and need for care in patients with an ostomy: a survey of 2647 patients of the Berlin OStomy-Study (BOSS). AB - BACKGROUND: Although ostomies are sometimes necessary, it is unclear which type of ostomy is advantageous for quality of life (QoL). In an observational study of 2647 patients, QoL after colostomy (CS) and small bowel stoma (SBS) formation was evaluated. METHODS: The European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30 and CR-38 questionnaires were used. Patient characteristics, retrospective information about the ostomy and previous treatments, and current stoma-related complications were recorded. All questionnaires were distributed and collected by stoma therapists at the homecare company PubliCare(r). RESULTS: In all, 1790 patients had a CS, and 756 had an SBS. The mean Global Health Score (mGHS-a general QoL indicator) was 52.33 in CS and 49.40 in SBS patients (p = 0.004), but the effect size (Cohen's d) was 0.1. In SBS patients, all functional scores were lower and most of the symptom scores were higher. CONCLUSIONS: QoL differed significantly for CS and SBS patients, but the effect size was marginal. The care of certain patient groups, particularly (female) patients who receive emergency surgeries, must be improved. More professional education and guidance are necessary for a larger proportion of patients. This survey provided reference data for quality of life in patients with an ostomy. PMID- 27659023 TI - Highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vectors for inactivation of hepatitis B virus. AB - CRISPR-Cas9-mediated genome-editing technology contributes not only to basic genomic studies but also to clinical studies such as genetic correction and virus inactivation. Hepatitis B virus (HBV) is a major target for potential application of CRISPR-Cas9 in eliminating viral DNA from human cells. However, the high stability of covalently closed circular DNA (cccDNA) makes it difficult to completely clear HBV infection. Here, we report highly multiplexed CRISPR-Cas9 nuclease and Cas9-nickase vector systems that simultaneously target three critical domains of the HBV genome. Co-transfection of an HBV-expressing plasmid and all-in-one CRISPR-Cas9 vectors resulted in significant reduction in viral replicative intermediates and extracellular hepatitis B surface and envelope antigens. In addition, successful fragmentation of the HBV genome was confirmed by DNA sequencing. Despite its high efficacy in suppressing HBV, no apparent off target mutations were detected by genomic cleavage detection assay and the small number of observed mutations was extremely rare and could only be detected by deep sequencing analysis. Thus, our all-in-one CRISPR-Cas9-nuclease and Cas9 nickase vectors present a model for simultaneous targeting of multiple HBV domains, potentially contributing to a well-designed therapeutic approach for curing HBV patients. PMID- 27659025 TI - Formulation and Characterization of Polysaccharide Microparticles for Pulmonary Delivery of Sodium Cromoglycate. AB - Sodium cromoglycate (SC) is an antiasthmatic and antiallergenic drug commonly used for chronic inhalation therapy; however, many daily intakes are required due to the fast drug clearance from airways. For these reasons, SC polymeric particles for inhalatory administration with adequate aerosolization and mucoadhesive properties were designed to prolong the drug residence time in the site of action. Sodium carboxymethylcellulose (CMCNa), sodium hyaluronate, and sodium alginate were selected to co-process SC by spray drying. The influence of these polysaccharides on the spray drying process and powder quality was evaluated (among others, morphology, size, moisture content, hygroscopicity, flowability, densities, liquid sorption, and stability). In vitro aerosolization, drug release, and mucoadhesion performance were also studied. Particularly, a novel method to comparatively evaluate the interaction between formulations and mucin solution (mucoadhesion test) was proposed as a rapid methodology to measure adhesion properties of inhalable particles, being the results as indicative of clearance probability. Among all the studied formulations, the powder based on SC and CMCNa exhibited the best mucoadhesion and aerosolization performance, the highest process yield and adequate moisture content, hygroscopicity, and stability. SC-CMCNa formulation arose as a promising inhalatory system to reduce the daily intakes and to increase the patient compliance. PMID- 27659026 TI - Hypothyroxinemia and Risk for Transient Tachypnea of Newborn. AB - Transient tachypnea of newborn is associated with hypothyroxinemia in animals via decreased stimulation of beta-adrenergic receptors and Na-K-ATPase activity. In 26 549 term neonates, serum total thyroxine <14 ug/dL, male sex, and elective cesarean delivery were significantly associated with greater risk for transient tachypnea of newborn. PMID- 27659027 TI - Variability in Response to Intravenous Immunoglobulin in the Treatment of Kawasaki Disease. AB - OBJECTIVES: To characterize the pattern of temperature response to intravenous immunoglobulin (IVIG) infusion in patients with Kawasaki disease (KD). STUDY DESIGN: Patients nonresponsive to IVIG (axillary temperature >=37.5 degrees C >24 hours after end of IVIG) were identified. Each patient with IVIG-nonresponsive KD was matched to a control patient with IVIG-responsive KD of the same age, sex, and duration of fever before IVIG. Hourly temperature profiles were obtained from immediately before the start of IVIG infusion until complete defervescence. RESULTS: A total of 182 patients nonresponsive to IVIG were matched (total n = 364). Nonresponders were further classified as partial nonresponders (68%) (axillary temperature decreased to <37.5 degrees C but fever recurred) and complete nonresponders (32%) (axillary temperature consistently >=37.5 degrees C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between responders and partial nonresponders (EST: -0.061 [0.007] degrees C/h, P < .001 for responders vs EST: -0.027 (0.012) degrees C/h, P = .03 for partial nonresponders [responders vs partial nonresponders, P = .65]), where EST is the parameter estimate from the regression model, representing the change in degrees Celsius for each hour since start of IVIG. In complete nonresponders, IVIG was not associated with significant decreases in temperature (EST: -0.008 [0.010] degrees C, P = .42). Factors associated with complete (vs partial) nonresponse included laboratory-confirmed infection, greater C-reactive protein, and IVIG brand. Defervescence in partial nonresponders was achieved with a second IVIG dose for 72% of patients compared with 58% of complete nonresponders (P = .001). Complete nonresponders were more likely to develop coronary artery aneurysms vs partial nonresponders (OR: 2.4 [1.1-5.4], P = .03) or responders (OR: 3.2 [1.5-6.9], P = .002). CONCLUSIONS: Nonresponse to initial IVIG can be further characterized by temperature profile, and complete nonresponders may require more aggressive second-line therapy. PMID- 27659028 TI - PHACE Syndrome: Consensus-Derived Diagnosis and Care Recommendations. PMID- 27659029 TI - Readmission following primary surgery for larynx and oropharynx cancer in the elderly. AB - OBJECTIVE: To examine 30-day readmission rates and associations with risk factors, survival, length of hospitalization, and costs in elderly patients with laryngeal and oropharyngeal squamous cell cancer (SCC). STUDY DESIGN: Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We evaluated 1,518 patients diagnosed with laryngeal or oropharyngeal SCC from 2004 to 2007 who underwent primary surgery using cross-tabulations, multivariate regression modeling, and survival analysis. RESULTS: Thirty-day readmission occurred in 14.1% of hospitalizations. Readmission was more likely in patients with postoperative complications during initial hospitalization (24.8% vs. 4.5%, P < 0.001), and was associated with an increased 30-day mortality incidence rate (5.1% vs. 0.9%; P < 0.001). On multivariate analysis, 30-day readmission was significantly associated with advanced stage (odds ratio [OR] = 1.81 [1.13-2.90]), comorbidity (OR = 2.69 [1.65 4.39]), divorced/separated marital status (OR = 2.00 [1.19-3.38]), preoperative tracheostomy (OR = 3.39 [1.55-7.44]), major surgical procedures (OR = 2.58 [1.68 3.97]), greater length of initial hospitalization (OR = 1.72 [1.09-2.71]), pneumonia (OR = 2.86 [1.28-6.40]), postoperative dysphagia (OR = 5.97 [2.48 15.83]), and cardiovascular events (OR = 5.84 [1.89-17.96]). Thirty-day readmission was significantly associated with 30-day mortality (OR = 5.89 [2.21 15.70) and higher 1-year mortality (68.0% vs. 89.2%, P < 0.001). The mean incremental costs of surgical care were significantly greater for patients with unplanned readmission ($15,123 [$10,514-$19,732]), after controlling for all other variables. CONCLUSION: Unplanned readmissions are associated with increased short- and long-term mortality and costs. Elderly patients with advanced disease, advanced comorbidity, lack of spousal support, pretreatment organ dysfunction, more extensive surgery, postoperative pneumonia, postoperative dysphagia, and prolonged hospitalization are at increased risk of 30-day readmission. These findings suggest a need for targeted interventions before, during, and after hospitalization to reduce morbidity, mortality, and excess costs in this high risk population. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:631-641, 2017. PMID- 27659030 TI - 3D in vitro co-culture models based on normal cells and tumor spheroids formed by cyclic RGD-peptide induced cell self-assembly. AB - OBJECTIVES: To design novel 3D in vitro co-culture models based on the RGD peptide-induced cell self-assembly technique. RESULTS: Multicellular spheroids from M-3 murine melanoma cells and L-929 murine fibroblasts were obtained directly from monolayer culture by addition of culture medium containing cyclic RGD-peptide. To reach reproducible architecture of co-culture spheroids, two novel 3D in vitro models with well pronounced core-shell structure from tumor spheroids and single mouse fibroblasts were developed based on this approach. The first was a combination of a RGD-peptide platform with the liquid overlay technique with further co-cultivation for 1-2 days. The second allowed co-culture spheroids to generate within polyelectrolyte microcapsules by cultivation for 2 weeks. M-3 cells (a core) and L-929 fibroblasts (a shell) were easily distinguished by confocal microscopy due to cell staining with DiO and DiI dyes, respectively. CONCLUSIONS: The 3D co-culture spheroids are proposed as a tool in tumor biology to study cell-cell interactions as well as for testing novel anticancer drugs and drug delivery vehicles. PMID- 27659031 TI - Technical difficulties and solutions of direct transesterification process of microbial oil for biodiesel synthesis. AB - Microbial oils are considered as alternative to vegetable oils or animal fats as biodiesel feedstock. Microalgae and oleaginous yeast are the main candidates of microbial oil producers' community. However, biodiesel synthesis from these sources is associated with high cost and process complexity. The traditional transesterification method includes several steps such as biomass drying, cell disruption, oil extraction and solvent recovery. Therefore, direct transesterification or in situ transesterification, which combines all the steps in a single reactor, has been suggested to make the process cost effective. Nevertheless, the process is not applicable for large-scale biodiesel production having some difficulties such as high water content of biomass that makes the reaction rate slower and hurdles of cell disruption makes the efficiency of oil extraction lower. Additionally, it requires high heating energy in the solvent extraction and recovery stage. To resolve these difficulties, this review suggests the application of antimicrobial peptides and high electric fields to foster the microbial cell wall disruption. PMID- 27659032 TI - Biodegradation of saline phenolic wastewater in a biological contact oxidation reactor with immobilized cells of Oceanimonas sp. AB - OBJECTIVE: To develop a method to treat saline phenolic wastewater in a biological contact oxidation reactor (BCOR) with immobilized cells of a marine microorganism, Oceanimonas sp., isolated from seawater. RESULTS: Cells were immobilized on fibre carriers in the BCOR. Saline wastewater with phenol at 1.5 g/l and NaCl at 6 % (w/v) was treated. In continuous assays, 99 % removal of phenol was achieved and a kinetic model for the phenol degradation is presented based on Monod's equation. CONCLUSION: The BOCR system using immobilized cells of Oceanimonas efficiently treats saline phenolic wastewaters without having decrease the salinity of the wastewater. PMID- 27659033 TI - Heterochrony and Morphological Variation of Epithalamic Asymmetry. AB - Heterochrony is one proposed mechanism to explain how morphological variation and novelty arise during evolution. To experimentally approach heterochrony in a comprehensive manner, we must consider all three aspects of developmental time (sequence, timing, duration). This task is only possible in developmental models that allow the acquisition of high-quality temporal data in the context of normalized developmental time. Here we propose that epithalamic asymmetry of teleosts is one such model. Comparative studies among related teleost species have revealed heterochronic shifts in the timing of ontogenic events leading to the development of epithalamic asymmetry. Such temporal changes involve neural structures critical for tissue-tissue interactions underlying the generation of asymmetry and are concurrent with the appearance of morphological differences in the pattern of asymmetry between species. Based on these findings, we hypothesize that interspecies variation of epithalamic asymmetry results from changes in the timing of tissue-tissue interactions critical for the establishment of asymmetry during ontogeny. Importantly, this hypothesis can be tested by systematic comparative approaches among teleosts species based on normalized developmental time, combined with experimental manipulation of epithalamic asymmetry development. PMID- 27659034 TI - Reducing the Matrix Effect in Organic Cluster SIMS Using Dynamic Reactive Ionization. AB - Dynamic reactive ionization (DRI) utilizes a reactive molecule, HCl, which is doped into an Ar cluster projectile and activated to produce protons at the bombardment site on the cold sample surface with the presence of water. The methodology has been shown to enhance the ionization of protonated molecular ions and to reduce salt suppression in complex biomatrices. In this study, we further examine the possibility of obtaining improved quantitation with DRI during depth profiling of thin films. Using a trehalose film as a model system, we are able to define optimal DRI conditions for depth profiling. Next, the strategy is applied to a multilayer system consisting of the polymer antioxidants Irganox 1098 and 1010. These binary mixtures have demonstrated large matrix effects, making quantitative SIMS measurement not feasible. Systematic comparisons of depth profiling of this multilayer film between directly using GCIB, and under DRI conditions, show that the latter enhances protonated ions for both components by 4- to ~15-fold, resulting in uniform depth profiling in positive ion mode and almost no matrix effect in negative ion mode. The methodology offers a new strategy to tackle the matrix effect and should lead to improved quantitative measurement using SIMS. Graphical Abstract ?. PMID- 27659036 TI - Sharks, ice cream, and neonatal seizures. PMID- 27659035 TI - Coeliac disease: immunogenicity studies of barley hordein and rye secalin-derived peptides. AB - Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A omega-gliadin/C hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of 3 H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. omega-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared. PMID- 27659037 TI - Role of laser irradiation in direct pulp capping procedures: a systematic review and meta-analysis. AB - A variety of materials are available to treat exposed dental pulp by direct pulp capping. The healing response of the pulp is crucial to form a dentin bridge and seal off the exposed pulp. Studies have used lasers to stimulate the exposed pulp to form tertiary dentin. The aim of the present systematic review and meta analysis was to evaluate the evidence on the effects of laser irradiation as an adjunctive therapy to stimulate healing after pulp exposure. A systematic literature search was conducted up to April 2016. A structured search using the keywords "Direct pulp capping," "Lasers," "Calcium hydroxide pulp capping," and "Resin pulp capping" was performed. Initially, 34 potentially relevant articles were identified. After removal of duplicates and screening by title, abstract, and full text when necessary, nine studies were included. Studies were assessed for bias and data were synthetized using a random-effects meta-analysis model. Six studies were clinical, and three were preclinical animal trials; the follow up period ranged from 2 weeks to 54 months. More than two thirds of the included studies showed that laser therapy used as an adjunct for direct pulp capping was more effective in maintaining pulp vitality than conventional therapy alone. Meta analysis showed that the success rate in the laser treatment group was significantly higher than the control group (log odds ratio = 1.737; 95 % confidence interval, 1.304-2.171). Lasers treatment of exposed pulps can improve the outcome of direct pulp capping procedures; a number of confounding factors may have influenced the outcomes of the included studies. PMID- 27659039 TI - 3D echocardiographic imaging of a septal myocardial cleft in hypertrophic cardiomyopathy. AB - Myocardial clefts are defined as narrow, deep blood-filled invaginations within the left ventricular myocardium. They occur in hypertrophic cardiomyopathy patients with different frequency and represent a distinctive morphological expression of hypertrophic cardiomyopathy. Although two-dimensional transthoracic echocardiography is able to detect myocardial clefts in some cases, cardiovascular magnetic resonance imaging with its high spatial resolution can detect myocardial clefts not visualized with echocardiography. In this report, we represent multimodality imaging of a septal myocardial cleft in a hypertrophic cardiomyopathy patient. PMID- 27659038 TI - Female Adult Aedes albopictus Suppression by Wolbachia-Infected Male Mosquitoes. AB - Dengue, chikungunya and zika viruses are pathogens with an increasing global impact. In the absence of an approved vaccine or therapy, their management relies on controlling the mosquito vectors. But traditional controls are inadequate, and the range of invasive species such as Aedes albopictus (Asian Tiger Mosquito) is expanding. Genetically modified mosquitoes are being tested, but their use has encountered regulatory barriers and public opposition in some countries. Wolbachia bacteria can cause a form of conditional sterility, which can provide an alternative to genetic modification or irradiation. It is unknown however, whether openly released, artificially infected male Ae. albopictus can competitively mate and sterilize females at a level adequate to suppress a field population. Also, the unintended establishment of Wolbachia at the introduction site could result from horizontal transmission or inadvertent female release. In 2014, an Experimental Use Permit from the United States Environmental Protection Agency approved a pilot field trial in Lexington, Kentucky, USA. Here, we present data showing localized reduction of both egg hatch and adult female numbers. The artificial Wolbachia type was not observed to establish in the field. The results are discussed in relation to the applied use of Wolbachia-infected males as a biopesticide to suppress field populations of Ae. albopictus. PMID- 27659041 TI - Disaster nursing experiences of Chinese nurses responding to the Sichuan Ya'an earthquake. AB - AIM: The aim of this study was to investigate the disaster experiences of nurses called to assist survivors one month after the 2013 Ya'an earthquake. BACKGROUND: China has experienced an increasing number of earthquake disasters in the past four decades. Although a health and disaster management system was initiated after the 2008 Wenchuan earthquake, nurses' roles and experiences in a disaster have been overlooked. METHODS: The researchers used qualitative descriptive design that included 16 participants. Data were collected using semi-structured interviews and observation notes, after which a qualitative content analysis was conducted. FINDINGS: Three major themes emerged: the process of being dispatched from hospitals to the disaster zone, the effort involved in getting to and working in the affected site and reflecting on the challenges they encountered. DISCUSSION: About half of the participants had received disaster nursing training before deploying to the disaster site, but they consistently expressed a lack of physical and psychological preparedness regarding the process of being dispatched from their hospitals to the disaster zone. LIMITATIONS: This was a single incident experience. Caution should be taken when trying to extend the findings to other parts of China. CONCLUSION: These findings highlighted the need for disaster in-service training as well as for having disaster plans in place. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Hospital and nursing leaders should provide disaster training opportunities that included topics such as compiling resource inventories, formulating disaster drills and simulations, managing emergencies, and using emergency communication methods. Health policy-makers should be required to prioritize capacity-building training for front-line nurses as well as to develop and implement disaster management plans to better prepare nurses for future disasters. PMID- 27659042 TI - Uncovering dispersion properties in semiconductor waveguides to study photon-pair generation. AB - We investigate the dispersion properties of ridge Bragg-reflection waveguides to deduce their phasematching characteristics. These are crucial for exploiting them as sources of parametric down-conversion (PDC). In order to estimate the phasematching bandwidth we first determine the group refractive indices of the interacting modes via Fabry-Perot experiments in two distant wavelength regions. Second, by measuring the spectra of the emitted PDC photons, we gain access to their group index dispersion. Our results offer a simple approach for determining the PDC process parameters in the spectral domain, and provide important feedback for designing such sources, especially in the broadband case. PMID- 27659040 TI - Characterizing the magnetic susceptibility tensor of lanthanide-containing polymethylated-DOTA complexes. AB - Lanthanide complexes based on the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraacetic acid) cage are commonly used as phase contrast agents in magnetic resonance imaging, but can also be utilized in structural NMR applications due to their ability to induce either paramagnetic relaxation enhancement or a pseudocontact shift (PCS) depending on the choice of the lanthanide. The size and sign of the PCS for any given atom is determined by its coordinates relative to the metal center, and the characteristics of the lanthanide's magnetic susceptibility tensor. Using a polymethylated DOTA tag (Ln-M8-SPy) conjugated to ubiquitin, we calculated the position of the metal center and characterized the susceptibility tensor for a number of lanthanides (dysprosium, thulium, and ytterbium) under a range of pH and temperature conditions. We found that there was a difference in temperature sensitivity for each of the complexes studied, which depended on the size of the lanthanide ion as well as the isomeric state of the cage. Using 17O-NMR, we confirmed that the temperature sensitivity of the compounds was enhanced by the presence of an apically bound water molecule. Since amide-containing lanthanide complexes are known to be pH sensitive and can be used as probes of physiological pH, we also investigated the effect of pH on the Ln-M8-SPy susceptibility tensor, but we found that the changes in this pH range (5.0-7.4) were not significant. PMID- 27659043 TI - The evidence for open and closed exocytosis as the primary release mechanism. AB - Exocytosis is the fundamental process by which cells communicate with each other. The events that lead up to the fusion of a vesicle loaded with chemical messenger with the cell membrane were the subject of a Nobel Prize in 2013. However, the processes occurring after the initial formation of a fusion pore are very much still in debate. The release of chemical messenger has traditionally been thought to occur through full distention of the vesicle membrane, hence assuming exocytosis to be all or none. In contrast to the all or none hypothesis, here we discuss the evidence that during exocytosis the vesicle-membrane pore opens to release only a portion of the transmitter content during exocytosis and then close again. This open and closed exocytosis is distinct from kiss-and-run exocytosis, in that it appears to be the main content released during regular exocytosis. The evidence for this partial release via open and closed exocytosis is presented considering primarily the quantitative evidence obtained with amperometry. PMID- 27659044 TI - No difference in range of motion between ultracongruent and posterior stabilized design in total knee arthroplasty: a randomized controlled trial. AB - PURPOSE: The use of an ultracongruent (UC) insert with a standard femoral component for substitution of the posterior cruciate ligament (PCL) is a bone preserving and therefore interesting alternative to the established box and cam mechanism of posterior stabilized (PS) total knee arthroplasty (TKA). This study investigated range of motion (ROM), stability and patient-reported outcome (PRO) in UC and PS TKA. We hypothesized better knee flexion with the PS design but no difference in stability and PRO between UC and PS TKA. METHODS: A randomized controlled study was performed. One hundred and twenty-seven patients were included, 63 with an UC and 64 with a PS TKA (Columbus, Aesculap, Tuttlingen, Germany). Intraoperative stability and range of motion was measured with the use of a navigation system. Patients were assessed before surgery, 3 months and 1 year postoperatively. RESULTS: There was no difference in ROM between both groups, neither intraoperatively nor at follow-up. There was 5 mm less sagittal translation at 90 degrees of knee flexion (p < 0.001) and more posterior femoral rollback during knee flexion in the PS TKA. Axial rotation between extension and knee flexion was reduced by both designs. UC TKA was 7 min faster (p = 0.001). At the one-year follow-up, the Knee Society Score was similar in both groups, the Oxford Knee Score demonstrated better results in the UC TKA group (p = 0.048). CONCLUSION: Increased intraoperative sagittal translation and reduced posterior femoral rollback during knee flexion of UC TKA seem to have no negative influence on short-term clinical outcome. Therefore, UC TKA seems to be a practical alternative to the established PS TKA for substitution of the PCL. This might be especially interesting for surgeons who do not always substitute the PCL. LEVEL OF EVIDENCE: I. PMID- 27659045 TI - IGFBP2 Activates the NF-kappaB Pathway to Drive Epithelial-Mesenchymal Transition and Invasive Character in Pancreatic Ductal Adenocarcinoma. AB - The molecular basis underlying the particularly aggressive nature of pancreatic ductal adenocarcinoma (PDAC) still remains unclear. Here we report evidence that the insulin-like growth factor-binding protein IGFBP2 acts as a potent oncogene to drive its extremely malignant character. We found that elevated IGFBP2 expression in primary tumors was associated with lymph node metastasis and shorter survival in patients with PDAC. Enforced expression of IGFBP2 promoted invasion and metastasis of PDAC cells in vitro and in vivo by inducing NF-kappaB dependent epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that IGFBP2 induced the nuclear translocation and phosphorylation of the p65 NF-kappaB subunit through the PI3K/Akt/IKKbeta pathway. Conversely, enforced expression of PTEN blunted this signaling pathway and restored an epithelial phenotype to PDAC cells in the presence of overexpressed IGFBP2. Overall, our results identify IGFBP2 as a pivotal regulator of an EMT axis in PDAC, the activation of which is sufficient to confer the characteristically aggressive clinical features of this disease. Cancer Res; 76(22); 6543-54. (c)2016 AACR. PMID- 27659046 TI - High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells. AB - Like classical chemotherapy regimens used to treat cancer, targeted therapies will also rely upon polypharmacology, but tools are still lacking to predict which combinations of molecularly targeted drugs may be most efficacious. In this study, we used image-based proliferation and apoptosis assays in colorectal cancer cell lines to systematically investigate the efficacy of combinations of two to six drugs that target critical oncogenic pathways. Drug pairs targeting key signaling pathways resulted in synergies across a broad spectrum of genetic backgrounds but often yielded only cytostatic responses. Enhanced cytotoxicity was observed when additional processes including apoptosis and cell cycle were targeted as part of the combination. In some cases, where cell lines were resistant to paired and tripled drugs, increased expression of antiapoptotic proteins was observed, requiring a fourth-order combination to induce cytotoxicity. Our results illustrate how high-order drug combinations are needed to kill drug-resistant cancer cells, and they also show how systematic drug combination screening together with a molecular understanding of drug responses may help define optimal cocktails to overcome aggressive cancers. Cancer Res; 76(23); 6950-63. (c)2016 AACR. PMID- 27659047 TI - UGT2B17 Expedites Progression of Castration-Resistant Prostate Cancers by Promoting Ligand-Independent AR Signaling. AB - Castration-resistant prostate cancer (CRPC) is characterized by a shift in androgen receptor (AR) signaling from androgen-dependent to androgen (ligand) independent. UDP-glucuronosyltransferase 2B17 (UGT2B17) is a key enzyme that maintains androgen homeostasis by catabolizing AR agonists into inactive forms. Although enhanced UGT2B17 expression by antiandrogens has been reported in androgen-dependent prostate cancer, its roles in regulating AR signaling transformation and CRPC progression remain unknown. In this study, we show that higher UGT2B17 protein expression in prostate tumors is associated with higher Gleason score, metastasis, and CRPC progression. UGT2B17 expression and activity were higher in androgen-independent compared to androgen-dependent cell lines. UGT2B17 stimulated cancer cell proliferation, invasion, and xenograft progression to CRPC after prolonged androgen deprivation. Gene microarray analysis indicated that UGT2B17 suppressed androgen-dependent AR transcriptional activity and enhanced of ligand-independent transcriptional activity at genes associated with cell mitosis. These UGT2B17 actions were mainly mediated by activation of the c Src kinase. In CRPC tumors, UGT2B17 expression was associated positively with c Src activation. These results indicate that UGT2B17 expedites CRPC progression by enhancing ligand-independent AR signaling to activate cell mitosis in cancer cells. Cancer Res; 76(22); 6701-11. (c)2016 AACR. PMID- 27659049 TI - Linezolid-associated reticulocytopenia. PMID- 27659048 TI - Cardiolipins Are Biomarkers of Mitochondria-Rich Thyroid Oncocytic Tumors. AB - Oncocytic tumors are characterized by an excessive eosinophilic, granular cytoplasm due to aberrant accumulation of mitochondria. Mutations in mitochondrial DNA occur in oncocytic thyroid tumors, but there is no information about their lipid composition, which might reveal candidate theranostic molecules. Here, we used desorption electrospray ionization mass spectrometry (DESI-MS) to image and chemically characterize the lipid composition of oncocytic thyroid tumors, as compared with nononcocytic thyroid tumors and normal thyroid samples. We identified a novel molecular signature of oncocytic tumors characterized by an abnormally high abundance and chemical diversity of cardiolipins (CL), including many oxidized species. DESI-MS imaging and IHC experiments confirmed that the spatial distribution of CLs overlapped with regions of accumulation of mitochondria-rich oncocytic cells. Fluorescent imaging and mitochondrial isolation showed that both mitochondrial accumulation and alteration in CL composition of mitochondria occurred in oncocytic tumors cells, thus contributing the aberrant molecular signatures detected. A total of 219 molecular ions, including CLs, other glycerophospholipids, fatty acids, and metabolites, were found at increased or decreased abundance in oncocytic, nononcocytic, or normal thyroid tissues. Our findings suggest new candidate targets for clinical and therapeutic use against oncocytic tumors. Cancer Res; 76(22); 6588-97. (c)2016 AACR. PMID- 27659050 TI - A proximity-dependent assay for specific RNA-protein interactions in intact cells. AB - The proximity ligation assay (PLA) is an immune staining method that detects protein-protein interactions in fixed cells. We describe here RNA-PLA, a simple adaptation of this technology that allows the detection of specific RNA-protein interactions in fixed cells by using a DNA oligonucleotide that hybridizes to a target RNA in combination with an antibody that recognizes the protein bound to the target RNA. Stable and transient RNA-protein interactions can be readily detected by generation of a fluorescent signal in discrete compartments in intact fixed cells with high specificity. We demonstrate that this approach requires the colocalization of the binding protein and its RNA target in the same cellular compartment, use of an oligonucleotide complementary to the target RNA, and the presence of a binding site for the protein in the target RNA. PMID- 27659051 TI - ARiBo pull-down for riboproteomic studies based on label-free quantitative mass spectrometry. AB - As part of their normal life cycle, most RNA molecules associate with several proteins that direct their fate and regulate their function. Here, we describe a novel method for identifying proteins that associate with a target RNA. The procedure is based on the ARiBo method for affinity purification of RNA, which was originally developed to quickly purify RNA with high yields and purity under native conditions. The ARiBo method was further optimized using in vitro transcribed RNA to capture RNA-associating proteins from cellular extracts with high yields and low background protein contamination. For these RNA pull-downs, stem-loops present in the immature forms of let-7 miRNAs (miRNA stem-loops) were used as the target RNAs. Label-free quantitative mass spectrometry analysis allowed for the reliable identification of proteins that are specific to the stem loops present in the immature forms of two miRNAs, let-7a-1 and let-7g. Several proteins known to bind immature forms of these let-7 miRNAs were identified, but with an improved coverage compared to previous studies. In addition, several novel proteins were identified that better define the protein interactome of the let-7 miRNA stem-loops and further link let-7 biogenesis to important biological processes such as development and tumorigenesis. Thus, combining the ARiBo pull down method with label-free quantitative mass spectrometry provides an effective proteomic approach for identification of proteins that associate with a target RNA. PMID- 27659052 TI - An intermolecular G-quadruplex as the basis for GTP recognition in the class V GTP aptamer. AB - Many naturally occurring or artificially created RNAs are capable of binding to guanine or guanine derivatives with high affinity and selectivity. They bind their ligands using very different recognition modes involving a diverse set of hydrogen bonding and stacking interactions. Apparently, the potential structural diversity for guanine, guanosine, and guanine nucleotide binding motifs is far from being fully explored. Szostak and coworkers have derived a large set of different GTP-binding aptamer families differing widely in sequence, secondary structure, and ligand specificity. The so-called class V-GTP aptamer from this set binds GTP with very high affinity and has a complex secondary structure. Here we use solution NMR spectroscopy to demonstrate that the class V aptamer binds GTP through the formation of an intermolecular two-layered G-quadruplex structure that directly incorporates the ligand and folds only upon ligand addition. Ligand binding and G-quadruplex formation depend strongly on the identity of monovalent cations present with a clear preference for potassium ions. GTP binding through direct insertion into an intermolecular G-quadruplex is a previously unobserved structural variation for ligand-binding RNA motifs and rationalizes the previously observed specificity pattern of the class V aptamer for GTP analogs. PMID- 27659054 TI - Virus-Like Particles Produced in Pichia Pastoris Induce Protective Immune Responses Against Coxsackievirus A16 in Mice. AB - BACKGROUND Coxsackievirus A16 (CA16) is one of the main causative agents of hand, foot, and mouth disease (HFMD), and the development of a safe and effective vaccine has been a top priority among CA16 researchers. MATERIAL AND METHODS In this study, we developed a Pichia pastoris yeast system for secretory expression of the virus-like particles (VLPs) for CA16 by co-expression of the P1 and 3CD proteins of CA16. SDS-PAGE, Western blot, and transmission electron microscopy (TEM) were performed to identify the formation of VLPs. Immunogenicity and vaccine efficacy of the CA16 VLPs were assessed in BABL/c mouse models. RESULTS Biochemical and biophysical analysis showed that the yeast-expressed CA16 VLPs were composed of VP0, VP1, and VP3 capsid subunit proteins, and present spherical particles with a diameter of 30 nm, similar to the parental infectious CA16 virus. Furthermore, CA16 VLPs elicited potent humoral and cellular immune responses, and VLPs-immunized sera conferred efficient protection to neonatal mice against lethal CA16 challenge. CONCLUSIONS Our results demonstrate that VLPs produced in Pichia pastoris represent a safe and effective vaccine strategy for CA16. PMID- 27659055 TI - Laparoscopic Adrenalectomy for Removal of Unilateral Noninvasive Pheochromocytomas in 10 Dogs. AB - OBJECTIVE: To report the surgical technique and outcome of dogs undergoing laparoscopic adrenalectomy for removal of unilateral noninvasive pheochromocytoma. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs with unilateral noninvasive adrenal tumors (n=10). METHODS: Medical records of dogs that underwent laparoscopic adrenalectomy for histologically confirmed pheochromocytoma were reviewed. Dogs were positioned in lateral recumbency with the table tilted up to create a semi-sternal position. Three or 4 ports were used and dissection of the mass proceeded using a combination of laparoscopic instrumentation, bipolar vessel-sealing devices, and in some cases monopolar electrosurgical probes. Conversion rate, complications, surgical time, hospitalization time, and long-term follow-up were recorded. RESULTS: The procedure was completed without the need for conversion in 9 of 10 dogs. In 1 dog, hemorrhage obscured the visual field and conversion to an open approach was elected. In 5 cases, a 3-port approach was used, and in 5 cases, a 4th port was placed. Median surgical time was 105 minutes (range, 65-250). Intraoperative complications included 1 splenic laceration. Postoperatively, 1 dog developed gastric dilatation-volvulus. All dogs were discharged from the hospital. Median follow-up time was 16.0 months (range, 6.9-38.0). CONCLUSION: With careful case selection, laparoscopic adrenalectomy for resection of pheochromocytoma was feasible and could be performed efficiently by experienced laparoscopic surgeons. PMID- 27659053 TI - Singlet glycine riboswitches bind ligand as well as tandem riboswitches. AB - The glycine riboswitch often occurs in a tandem architecture, with two ligand binding domains (aptamers) followed by a single expression platform. Based on previous observations, we hypothesized that "singlet" versions of the glycine riboswitch, which contain only one aptamer domain, are able to bind glycine if appropriate structural contacts are maintained. An initial alignment of 17 putative singlet riboswitches indicated that the single consensus aptamer domain is flanked by a conserved peripheral stem-loop structure. These singlets were sorted into two subtypes based on whether the active aptamer domain precedes or follows the peripheral stem-loop, and an example of each subtype of singlet riboswitch was characterized biochemically. The singlets possess glycine-binding affinities comparable to those of previously published tandem examples, and the conserved peripheral domains form A-minor interactions with the single aptamer domain that are necessary for ligand-binding activity. Analysis of sequenced genomes identified a significant number of singlet glycine riboswitches. Based on these observations, we propose an expanded model for glycine riboswitch gene control that includes singlet and tandem architectures. PMID- 27659056 TI - Targeting astrocytes in brain injuries: A translational research approach. AB - In the brain, the astrocentric view has increasingly changed in the past few years. The classical and old view of astrocytes as "just supporting cells" has assigned these cells some functions to help neurons maintain their homeostasis. This neuronal supportive function of astrocytes includes maintenance of ion and extracellular pH equilibrium, neuroendocrine signaling, metabolic support, clearance of glutamate and other neurotransmitters, and antioxidant protection. However, recent findings have shed some light on the new roles, some controversial though, performed by astrocytes that might change our view about the central nervous system functioning. Since astrocytes are important for neuronal survival, it is a potential approach to favor astrocytic functions in order to improve the outcome. Such translational strategies may include the use of genetically targeted proteins, and/or pharmacological therapies by administering androgens and estrogens, which have shown promising results in vitro and in vivo models. It is noteworthy that successful strategies reviewed in here shall be extrapolated to human subjects, and this is probably the next step we should move on. PMID- 27659057 TI - Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound. AB - BACKGROUND: In patients with rheumatoid arthritis (RA) clinical measures of disease activity may not reliably discriminate between patients with active inflammatory disease and those with concomitant fibromyalgia (FM). Recent work has shown RA patients with a 28 tender joint count (TJC) minus swollen joint count (SJC) of 7 or more (joint count criteria) are more likely to meet classification criteria for FM. This study aimed to determine whether RA patients meeting clinical criteria for FM had lower levels of joint inflammation as determined by ultrasound (US). METHODS: RA patients with DAS28 > 2.6 were recruited. Patients underwent clinical assessment including ultrasound examination of the hands and wrists with quantification of grey scale (GS) and power Doppler (PD) synovitis. Patients completed questionnaires to assess pain, fatigue, disability and psychological comorbidity. RESULTS: Patients meeting either of the FM criteria had higher scores for disease activity, depression, disability and fatigue. Those meeting both the joint count and classification FM criteria had significantly lower levels of GS and PD inflammation on US. CONCLUSIONS: RA patients with concomitant FM, as determined by widespread soft tissue tenderness but fewer clinically inflamed joints, have higher disease activity scores but may have lower levels of synovial inflammation on US. This has implications for the identification and management of these patients who may not respond to conventional therapy and hence be more suitable for alternative approaches to treatment. PMID- 27659058 TI - Risk of erectile dysfunction associated with use of 5-alpha reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink. AB - OBJECTIVE: To estimate the risk of erectile dysfunction in men who used 5-alpha reductase inhibitors to treat benign prostatic hyperplasia or alopecia. DESIGN: Cohort studies with nested case-control analyses. SETTING: UK Clinical Practice Research Datalink. POPULATION: Two populations of men free of risk factors for erectile dysfunction and other sexual dysfunction or its treatment: men aged 40 or more with benign prostatic hyperplasia who received a prescription for a 5 alpha reductase inhibitor (finasteride or dutasteride) or alpha blocker, or both, and men aged 18-59 with alopecia. EXPOSURES: In the benign prostatic hyperplasia study, exposures were classified as 5-alpha reductase inhibitors only, 5-alpha reductase inhibitors+alpha blockers, or alpha blockers only. In the alopecia study, exposures were finasteride 1 mg or no treatment. MAIN OUTCOME MEASURES: Cases were men with a diagnosis of erectile dysfunction or treatment (procedure or prescription for a phosphodiesterase type 5 inhibitor) during follow-up. We calculated incidence rates and adjusted incidence rate ratios with 95% confidence intervals. We also conducted nested case-control analyses to control for major confounders, and calculated adjusted odds ratios with 95% confidence intervals. RESULTS: In the population with benign prostatic hyperplasia (n=71 849), the risk of erectile dysfunction was not increased with use of 5-alpha reductase inhibitors only (incidence rate ratio 0.92, 95% confidence interval 0.85 to 0.99; odds ratio 0.94, 95% confidence interval 0.85 to 1.03) or 5-alpha reductase inhibitors+alpha blocker (1.09, 0.99 to 1.21, 0.92; 0.80 to 1.06) compared with alpha blockers only, and remained null regardless of number of prescriptions or timing of use. The risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia, regardless of exposure. For the alopecia population (n=12 346), the risk of erectile dysfunction was not increased for users of finasteride 1 mg compared with unexposed men with alopecia (1.03, 0.73 to 1.44; 0.95, 0.64 to 1.41). CONCLUSION: 5-alpha reductase inhibitors do not seem to significantly increase the risk of incident erectile dysfunction, regardless of indication for use. Risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia. PMID- 27659059 TI - VOC exposures in California early childhood education environments. AB - Little information exists about exposures to volatile organic compounds (VOCs) in early childhood education (ECE) environments. We measured 38 VOCs in single-day air samples collected in 2010-2011 from 34 ECE facilities serving California children and evaluated potential health risks. We also examined unknown peaks in the GC/MS chromatographs for indoor samples and identified 119 of these compounds using mass spectral libraries. VOCs found in cleaning and personal care products had the highest indoor concentrations (d-limonene and decamethylcyclopentasiloxane [D5] medians: 33.1 and 51.4 MUg/m3, respectively). If reflective of long-term averages, child exposures to benzene, chloroform, ethylbenzene, and naphthalene exceeded age-adjusted "safe harbor levels" based on California's Proposition 65 guidelines (10-5 lifetime cancer risk) in 71%, 38%, 56%, and 97% of facilities, respectively. For VOCs without health benchmarks, we used information from toxicological databases and quantitative structure-activity relationship models to assess potential health concerns and identified 12 VOCs that warrant additional evaluation, including a number of terpenes and fragrance compounds. While VOC levels in ECE facilities resemble those in school and home environments, mitigation strategies are warranted to reduce exposures. More research is needed to identify sources and health risks of many VOCs and to support outreach to improve air quality in ECE facilities. PMID- 27659060 TI - A novel affinity-based method for the isolation of highly purified extracellular vesicles. AB - Extracellular vesicles (EVs) such as exosomes and microvesicles serve as messengers of intercellular network, allowing exchange of cellular components between cells. EVs carry lipids, proteins, and RNAs derived from their producing cells, and have potential as biomarkers specific to cell types and even cellular states. However, conventional methods (such as ultracentrifugation or polymeric precipitation) for isolating EVs have disadvantages regarding purity and feasibility. Here, we have developed a novel method for EV purification by using Tim4 protein, which specifically binds the phosphatidylserine displayed on the surface of EVs. Because the binding is Ca2+-dependent, intact EVs can be easily released from Tim4 by adding Ca2+ chelators. Tim4 purification, which we have applied to cell conditioned media and biofluids, is capable of yielding EVs of a higher purity than those obtained using conventional methods. The lower contamination found in Tim4-purified EV preparations allows more EV-specific proteins to be detected by mass spectrometry, enabling better characterization and quantification of different EV populations' proteomes. Tim4 protein can also be used as a powerful tool for quantification of EVs in both ELISA and flow cytometry formats. Thus, the affinity of Tim4 for EVs will find abundant applications in EV studies. PMID- 27659061 TI - A cross-sectional study on the concordance between vaginal HPV DNA detection and type-specific antibodies in a multi-ethnic cohort of women from Amsterdam, the Netherlands - the HELIUS study. AB - BACKGROUND: Acquisition of genital human papillomavirus (HPV) infection is common among the young, sexually active population. Genital HPV infections do not always lead to seroconversion. We aimed to assess the association between cervico vaginal high risk (hr) HPV DNA and type-specific antibodies in an ethnically diverse cohort of young women. METHODS: Women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan and Turkish origin participating in a large-scale multi-ethnic population-based cohort (the HELIUS study) provided vaginal self-samples and blood samples, and completed a questionnaire regarding demographics, lifestyle and sexual health. Vaginal swabs were tested for HPV using the highly sensitive SPF10-PCR DEIA/LiPA25 system (version1). Serum samples were tested for type-specific L1 antibodies against 7 hrHPV types (16,18,31,33,45,52,58) with multiplex serology. We assessed the association between vaginal HPV DNA and type-specific seropositivity with logistic and linear regression, using generalized estimating equations (GEE). We determined whether this association varies by ethnicity by adding an interaction term. RESULTS: We selected 532 women who completed the questionnaire, provided a vaginal swab and a blood sample. Their median age was 27 years (interquartile range 24-31 years). Prevalence of DNA of any of the 7 hrHPV was 22 %; HPV-52 was most common. Prevalence of antibodies against one or more hrHPV types was 24 %; HPV-16 seropositivity was most common. In multivariable logistic regression analysis using GEE, adjusting for other determinants, vaginal HPV DNA detection was associated with type-specific HPV seropositivity (OR 1.53, 95 % CI 1.06-2.20). In multivariable linear regression analysis using GEE, the geometric mean of type specific antibody reactivity was 1.15 (95 % CI 1.04-1.27) times higher in women positive for HPV DNA compared to HPV DNA-negative women. There was little evidence that ethnicity modified the association between HPV DNA, and type specific seropositivity, or with antibody reactivities (p = 0.47 and p = 0.57, respectively). CONCLUSIONS: In this multi-ethnic group of young women in Amsterdam, cervico-vaginal hrHPV DNA detection was an independent determinant of type-specific HPV seropositivity. PMID- 27659063 TI - An efficient method for generating a germ cell depleted animal model for studies related to spermatogonial stem cell transplantation. AB - BACKGROUND: Spermatogonial stem cell (SSC) transplantation (SSCT) has become important for conservation of endangered species, transgenesis and for rejuvenating testes which have lost germ cells (Gc) due to gonadotoxic chemotherapy or radiotherapy during the prepubertal phase of life. Creating a germ cell-depleted animal model for transplantation of normal or gene-transfected SSC is a prerequisite for such experimental studies. Traditionally used intraperitoneal injections of busulfan to achieve this are associated with painful hematopoietic toxicity and affects the wellbeing of the animals. Use of testicular busulfan has been reported recently to avoid this but with a very low success rate of SSCT. Therefore, it is necessary to establish a more efficient method to achieve higher SSCT without any suffering or mortality of the animals. METHODS: A solution of busulfan, ranging from 25 MUg/20 MUl to 100 MUg/20 MUl in 50 % DMSO was used for this study. Each testis received two diagonally opposite injections of 10 MUl each. Only DMSO was used as control. Germ cell depletion was checked every 15 days. GFP-expressing SSC from transgenic donor mice C57BL/6-Tg (UBC-GFP) 30Scha/J were transplanted into busulfan-treated testis. Two months after SSCT, mice were analyzed for presence of colonies of donor-derived SSC and their ability to generate offspring. RESULTS: A dose of 75 MUg of busulfan resulted in reduction of testis size and depletion of the majority of Gc of testis in all mice within 15 days post injection without causing mortality or a cytotoxic effect in other organs. Two months after SSCT, colonies of donor derived Gc-expressing GFP were observed in recipient testes. When cohabitated with females, donor-derived offspring were obtained. By our method, 71 % of transplanted males sired transgenic progeny as opposed to 5.5 % by previously described procedures. About 56 % of progeny born were transgenic by our method as opposed to 1.2 % by the previously reported methods. CONCLUSIONS: We have established an efficient method of generating a germ cell-depleted animal model by using a lower dose of busulfan, injected through two diagonally opposite sites in the testis, which allows efficient colonization of transplanted SSC resulting in a remarkably higher proportion of donor-derived offspring generation. PMID- 27659062 TI - Depth-dependence of visual signals in the human superior colliculus at 9.4 T. AB - The superior colliculus (SC) is a layered structure located in the midbrain. We exploited the improved spatial resolution and BOLD signal strength available at 9.4 T to investigate the depth profile of visual BOLD responses in the human SC based on distortion-corrected EPI data with a 1 mm isotropic resolution. We used high resolution (350 um in-plane) anatomical images to determine regions-of interest of the SC and applied a semi-automated method to segment it into superficial, intermediate, and deep zones. A greater than linear increase in sensitivity of the functional signal at 9.4 T allowed us to detect a statistically significant depth pattern in a group analysis with a 20 min stimulation paradigm. Descriptive data showed consistent depth profiles also in single individuals. The highest signals were localized to the superficial layers of the right and left SC during contralateral stimulation, which was in good agreement with its functional architecture known from non-human primates. This study thus demonstrates the potential of 9.4 T MRI for functional neuroimaging even in deeply located, particularly challenging brain structures such as the SC. Hum Brain Mapp 38:574-587, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27659064 TI - Low-oxygen waters limited habitable space for early animals. AB - The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (~550-541 Ma). In combination with Fe based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 MUM) was a key requirement for the development of early animal-based ecosystems. PMID- 27659065 TI - Schizophyllum commune has an extensive and functional alternative splicing repertoire. AB - Recent genome-wide studies have demonstrated that fungi possess the machinery to alternatively splice pre-mRNA. However, there has not been a systematic categorization of the functional impact of alternative splicing in a fungus. We investigate alternative splicing and its functional consequences in the model mushroom forming fungus Schizophyllum commune. Alternative splicing was demonstrated for 2,285 out of 12,988 expressed genes, resulting in 20% additional transcripts. Intron retentions were the most common alternative splicing events, accounting for 33% of all splicing events, and 43% of the events in coding regions. On the other hand, exon skipping events were rare in coding regions (1%) but enriched in UTRs where they accounted for 57% of the events. Specific functional groups, including transcription factors, contained alternatively spliced genes. Alternatively spliced transcripts were regulated differently throughout development in 19% of the 2,285 alternatively spliced genes. Notably, 69% of alternatively spliced genes have predicted alternative functionality by loss or gain of functional domains, or by acquiring alternative subcellular locations. S. commune exhibits more alternative splicing than any other studied fungus. Taken together, alternative splicing increases the complexity of the S. commune proteome considerably and provides it with a rich repertoire of alternative functionality that is exploited dynamically. PMID- 27659066 TI - A novel animal model for skin flap prelamination with biomaterials. AB - Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible. PMID- 27659067 TI - Whether G-CSF administration has beneficial effect on the outcome after assisted reproductive technology? A systematic review and meta-analysis. AB - BACKGROUND: Previous studies have explored the effect of granulocyte colony stimulating factor (G-CSF) administration on the outcome of assisted reproductive technology (ART), and came into controversial conclusions. The present meta analysis aims to assess whether G-CSF administration has beneficial effect on the outcome after ART. METHOD: The electronic databases Pubmed, Embase and Google Scholar were searched up to May 2016. Articles that studied the effect of G-CSF administration on the outcome after ART were included in the present meta analysis. Odds ratio (OR) with 95 % confidence interval (95 % CI) were calculated to assess the effect of G-CSF administration on the outcome after ART. The outcomes of interest were implantation rate (IR) and pregnancy rate (PR). RESULTS: Four cohort studies with 1101 embryos transplantation assessed the effect of G-CSF administration on IR and 6 studies with 621 cycles assessed the role of G-CSF administration in PR. Meta-analysis did not found an increased embryo IR in G-CSF administration cycles [OR 1.59 (95 % CI 0.74-3.41). whereas the PR with G-CSF administration was significantly higher compared with cases without G-CSF administration [OR 2.03 (95 % CI 1.19-3.46)]. Additionally, we found that G-CSF administrated subcutaneously resulted in significantly higher PR [OR 3.12 (95 % CI 1.67-5.81)] and IR [OR 2.82 (95 % CI 1.29-6.15)] compared with control group, whereas G-CSF administrated via local uterine infusion had no beneficial effect on the PR [OR 1.42 (95 % CI 0.91-2.24)] and IR [OR 1.10 (95 % CI 0.76-1.60)] after ART. CONCLUSIONS: G-CSF administration may have beneficial effect on clinical pregnancy outcome after ART. Subcutaneous injection may be an optimal route of G-CSF administration. Further cohort studies are required to explore the mechanisms undergone the effect and investigate the best route and dose of G-CSF administration. PMID- 27659068 TI - The volleyball athlete's shoulder: biomechanical adaptations and injury associations. AB - In volleyball, the dominant shoulder of the athlete undergoes biomechanical and morphological adaptations; however, definitive conclusions about their exact nature, aetiology, purpose and associations with shoulder injury have not been reached. We present a systematic review of the existing literature describing biomechanical adaptations in the dominant shoulders of volleyball players and factors that may predispose to shoulder pain/injury. A thorough literature search via Medline, EMBASE and SCOPUS was conducted for original studies of volleyball players and 15 eligible articles were identified. Assessment of study quality was performed using the STROBE statement. The reviewed literature supports the existence of a glenohumeral internal rotation deficit (GIRD) and a possible (and less pronounced) external rotation gain in the dominant vs. the non-dominant shoulder of volleyball athletes. Unlike other overhead sports, the GIRD in volleyball athletes appears to be anatomical as a response to the repetitive overhead movements and not to be associated with shoulder pain/injury. Additionally, the dominant shoulder exhibits muscular imbalance, which appears to be a significant risk factor for shoulder pain. Strengthening of the external rotators should be used alongside shoulder stretching and joint mobilisations, core strengthening and optimisation of spike technique as part of injury management and prevention programmes. PMID- 27659069 TI - Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis. AB - Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. However, the diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. A systematic search was performed to identify eligible articles for analysis. The pooled OR showed that SFRP1, SFRP2, SFRP4 and SFRP5 methylation was significantly higher in CRC and benign mucosal lesions than in normal colonic mucosa. When CRC was compared to benign mucosal lesions, SFRP1 and SFRP2 methylation had a significantly higher OR, but methylated SFRP4 and SFRP5 had a similar OR. Moreover, the pooled sensitivity, specificity and AUC (area under the curve) of methylated SFRP2 in feces of patients with CRC vs. healthy subjects was 0.71, 0.94 and 0.94, respectively. Therefore, methylation of SFRP1 and SFRP2 may be significantly correlated with CRC. However, in a study with small sample size, methylated SFRP4 and SFRP5 were not shown to be closely associated with CRC. Additionally, detection of SFRP2 methylation in feces presents a potential noninvasive biomarker for CRC diagnosis. PMID- 27659070 TI - Characterization and Comparative Genomic Analyses of Pseudomonas aeruginosa Phage PaoP5: New Members Assigned to PAK_P1-like Viruses. AB - As a potential alternative to antibiotics, phages can be used to treat multi-drug resistant bacteria. As such, the biological characteristics of phages should be investigated to utilize them as effective antimicrobial agents. In this study, phage PaoP5, a lytic virus that infects Pseudomonas aeruginosa PAO1, was isolated and genomically characterized. PaoP5 comprises an icosahedral head with an apex diameter of 69 nm and a contractile tail with a length of 120 nm. The PaoP5 genome is a linear dsDNA molecule containing 93,464 base pairs (bp) with 49.51% G + C content of 11 tRNA genes and a 1,200 bp terminal redundancy. A total of 176 protein-coding genes were predicted in the PaoP5 genome. Nine PaoP5 structural proteins were identified. Three hypothetical proteins were determined as structural. Comparative genomic analyses revealed that seven new Pseudomonas phages, namely, PaoP5, K8, C11, vB_PaeM_C2-10_Ab02, vB_PaeM_C2-10_Ab08, vB_PaeM_C2-10_Ab10, and vB_PaeM_C2-10_Ab15, were similar to PAK_P1-like viruses. Phylogenetic and pan-genome analyses suggested that the new phages should be assigned to PAK_P1-like viruses, which possess approximately 100 core genes and 150 accessory genes. This work presents a detailed and comparative analysis of PaoP5 to enhance our understanding of phage biology. PMID- 27659072 TI - The effects of ordered carbon vacancies on stability and thermo-mechanical properties of V8C7 compared with VC. AB - The ordered non-stoichiometric V8C7 can form in the VCy carbides by the disorder order phase transformation. The intrusion of ordered carbon vacancies can affect their stability, mechanical, thermal and electronic properties. The relatively thermodynamic stability and mechanical properties at high temperature for the ordered stoichiometric VC and non-stoichiometric V8C7 are investigated in this paper by first-principle calculations combined with the quasi-harmonic approximation. The difference between the properties of VC and V8C7 can be obtained. We find that the V8C7 is thermodynamic more stable than VC, but has weaker elastic heat resistance than VC. Moreover, the minimum thermal conductivity of VC is a little larger than V8C7 and a simple way is proposed to characterize the anisotropy of lattice thermal conductivity based on the Cahill's model. PMID- 27659071 TI - Nonvitamin K antagonist oral anticoagulant activity: challenges in measurement and reversal. AB - BACKGROUND: Four nonvitamin K antagonist oral anticoagulants (NOACs) are approved for the prevention of stroke in patients with nonvalvular atrial fibrillation and for the treatment of venous thromboembolism. These include the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. Bleeding is a complication for all anticoagulants and concerns regarding bleeding risk and the suitability of effective reversal strategies may be a barrier to their prescription. Despite the reduced risk of bleeding compared with vitamin K antagonists, questions persist regarding the management of bleeding related to NOAC use. MAIN TEXT: To date, although a number of assays are responsive to NOACs, no single routine laboratory test has been identified to accurately measure the clinical anticoagulation state of patients on NOACs or established as a reliable predictor of bleeding risk. In addition, the establishment of a reliable human bleeding model to test novel inhibitors of the coagulation cascade has proved challenging. Although routine monitoring of anticoagulant levels is not necessary in patients taking NOACs, anticoagulant reversal and a means of measuring reversal may be required for patients who present with bleeding or require urgent surgery. Prothrombin complex concentrates are pooled plasma products containing varying amounts of inactive vitamin K dependent clotting factors in addition to vitamin K-dependent proteins and can replenish factors in the intrinsic and extrinsic coagulation cascade, reversing an anticoagulant effect. Only one agent, idarucizumab, has been approved for rapid reversal of dabigatran-induced anticoagulation and one more agent, andexanet alfa, has been submitted for approval to reverse the anticoagulatory effects of direct and indirect factor Xa inhibitors. CONCLUSIONS: This review discusses the laboratory tests available for assessing anticoagulation, human models of bleeding, and the use of current strategies-including prothrombin complex concentrates for reversal of anticoagulation by NOACs-to manage bleeding in patients. PMID- 27659073 TI - Cross-Linkable Hole-Transport Materials Improve the Device Performance of Perovskite Light-Emitting Diodes. AB - Hybrid organic/inorganic perovskites are promising candidate materials for use in photovoltaic applications. More recently, they have also become highly attractive as active materials for other optoelectronic devices, including lasers, light emitting diodes, and photodetectors. Nevertheless, difficulties in forming continuous and uniform films and the existence of a charge-injection barrier between the perovskite layer and the electrodes have hindered the development of high-performance perovskite light-emitting diodes (PeLEDs). In this study, a cross-linked hole-transport layer (HTL) is introduced to improve the hole injection efficiency of PeLEDs. Furthermore, this layer simultaneously facilitates the formation of smooth perovskite layers, presumably because of the different surface energies. More interestingly, the HTL also exhibits strong solvent effects on the device performance. When the processing solvent for fabricating the HTLs is changed from chlorobenzene to N,N-dimethylformamide (DMF), the perovskite layer becomes more uniform and continuous, leading to better surface coverage and higher device efficiency, presumably because DMF has strong affinity toward the perovskite precursors. The approach presented herein could become a general method for decreasing the hole-injection barrier of PeLEDs and, eventually, lead to higher device performance. PMID- 27659074 TI - Cancellous and cortical bone mineral density around an elastic press-fit socket in total hip arthroplasty. AB - Background and purpose - The acetabular component has remained the weakest link in hip arthroplasty for achievement of long-term survival. One of the possible explanatory factors for acetabular failure has been acetabular stress shielding. For this, we investigated the effects of a cementless elastic socket on acetabular bone mineral density (BMD). Patients and methods - During 2008-2009, we performed a single-center prospective cohort trial on 25 patients (mean age 64 (SD 4), 18 females) in whom we implanted a cementless elastic press-fit socket. Using quantitative BMD measurements on CT, we determined the change in BMD surrounding the acetabular component over a 2-year follow-up period. Results - We found a statistically significant decrease in cancellous BMD (-14% to -35%) and a stable level of cortical BMD (5% to -5%) surrounding the elastic press-fit cup during the follow-up period. The main decrease was seen during the first 6 months after implantation. During the second year, cancellous BMD showed a further decrease in the medial and lower acetabular regions. Interpretation - We found no evidence that an elastic press-fit socket would prevent acetabular stress shielding during a 2-year follow-up. PMID- 27659075 TI - Effects of the Residues from the Endodontic Sealers on the Longevity of Esthetic Restorations. AB - The substances used in the root canal treatment, especially sodium hypochlorite solution and oxidant agents, can negatively interfere on the bond strength of the adhesive systems to dentin and on the dental crowns fracture resistance.(1,2). PMID- 27659076 TI - Prevalence of Candida spp. in Healthy Oral Mucosa Surfaces with Higher Incidence of Chronic Hyperplastic Candidosis. AB - INTRODUCTION: Predisposing factors in chronic hyperplastic candidosis (CHC) have been poorly recognized. This study aimed at assessing the prevalence of Candida spp. in areas of the oral mucosa showing greater prevalent rate of CHC, such as the retrocomissural area, the lateral borders of the tongue, and the hard-palate mucosa in four groups of individuals presenting predisposing factors as follows: Smoking habits (group I); patients with low salivary flow rate (SFR) (hyposalivation - group II); patients with loss of vertical dimension of occlusion (LVDO -group III); and control subjects (group IV). MATERIALS AND METHODS: A total of 44 individuals (age 4090 years, mean: 55.8 years) were divided into four groups: Group I (11 smokers); group II (10 hyposalivation patients); group III (10 LVDO patients); and group IV (control, 13 healthy subjects). All individuals were tested for Candida-pseudohyphae form by direct examination and for Candida spp. culture growth in samples obtained from the retrocomissural, tongue's lateral border, and hard-soft palatal mucosa. RESULTS: Direct examination showed a statistically significant prevalence rate for pseudohyphae (p < 0.05) on the retrocomissural and on tongue's lateral borders of individuals with LVDO. A statistically significant (p < 0.05) culture growth for Candida spp. was found on the retrocomissural areas of those with hyposalivation and with LVDO, and on the palate mucosa and on the tongue's lateral borders in the smokers and in the individuals with LVDO when compared with those of the control group. CONCLUSION: While direct examination is effective for detecting pseudohyphae, LVDO and tobacco smoking seem to be factors of relevance to the development of CHC. CLINICAL SIGNIFICANCE: Since CHC has been linked to a high rate of malignant transformation, this study analyzes some clinical (and exogenous) factors that may contribute to the development of CHC and addresses some preventive measures to reduce its incidence. PMID- 27659078 TI - Failure Rates of Orthodontic Fixed Lingual Retainers bonded with Two Flowable Light-cured Adhesives: A Comparative Prospective Clinical Trial. AB - INTRODUCTION: This comparative prospective randomized clinical trial examined the in vivo failure rates of fixed mandibular and maxillary lingual retainers bonded with two light-cured flowable composites over 6 months. MATERIALS AND METHODS: Consecutive patients were divided into two groups on a 1:1 basis. Two hundred fixed lingual retainers were included, and their failures were followed for 6 months. One group (n = 50) received retainers bonded with a nano-hybrid composite based on nano-optimized technology (Tetric-N-Flow, Ivoclar Vivadent). Another group (n = 50) received retainers bonded with a low viscosity (LV) composite (Transbond Supreme LV, 3M Unitek). RESULTS: There was no significant difference between the overall failure rates of mandibular retainers bonded with Transbond (8%) and those bonded with Tetric-N-Flow (18%). However, the odds ratio for failure using Tetric-N-flow was 2.52-fold greater than that of Transbond. The failure rate of maxillary retainers bonded with Transbond was higher (14%), but not significantly different, than that of maxillary retainers bonded with Tetric N-flow (10%). There was no significant difference in the estimated mean survival times of the maxillary and mandibular retainers bonded with the two composites. CONCLUSION: Both types of composites tested in the current study can be used to bond fixed maxillary and mandibular lingual retainers, with low failure rates. PMID- 27659077 TI - Cone Beam Computed Tomography-based Evaluation of the Anterior Teeth Position Changes obtained by Passive Self-ligating Brackets. AB - AIM: The objective of this study was to evaluate the anterior teeth position changes obtained by passive self-ligating brackets using cone beam computed tomography (CBCT). MATERIALS AND METHODS: Twenty patients with a mean age of 16.5 years, class I malocclusion, constricted maxillary arch, and teeth crowding above 5 mm were enrolled in this study, and treated by passive orthodontic self ligating brackets. A sequence of stainless steel thermoset wire was implemented with ending wire of 0.019" * 0.025". The CBCT and dental casts were obtained prior to the installation of orthodontic appliances (T1), and 30 days after rectangular steel wire 0.019" * 0.025" installation (T2). The measurements in CBCT were performed with the Anatomage software, and the dental casts were evaluated with a digital caliper rule with an accuracy of 0.01 mm. RESULTS: The CBCT data demonstrated mean buccal inclination of the upper and lower central incisors ranging from 6.55 degrees to 7.24 degrees respectively. The upper and lower lateral incisors ranged from 4.90 degrees to 8.72 degrees respectively. The lower canines showed an average increase of 3.88 degrees in the buccal inclination and 1.96 mm in the transverse intercuspal distance. The upper canines showed a negative inclination with mean average of -0.36 degrees , and an average increase of 0.82 mm in the transverse distance, with negative correlation with the initial crowding. CONCLUSION: Treatment with passive self-ligating brackets without obtaining spaces increases buccal inclination of the upper and lower incisors with no correlation with the amount of initial teeth crowding. The intercanine distance tends to a small increase showing different inclinations between the arches. CLINICAL SIGNIFICANCE: When taking into account the self ligating brackets, the amount of initial dental crowding is not a limitation factor that could increase the buccal inclination of the anterior teeth. PMID- 27659079 TI - Nano-hydroxyapatite could Compensate the Adverse Effect of soft carbonated Drinks on Enamel. AB - INTRODUCTION: Since one of the most important disadvantages of soft drinks includes their adverse effect on mineral content of enamel because of their low pH, this study examined the microhardness of enamel before and after exposure to a soft drink containing different concentrations of nano-hydroxyapatite (nano-HA) as an additive. MATERIALS AND METHODS: Sixty caries free human premolars were mounted in epoxy resin. After polishing, the baseline micro-hardness was recorded three times for each specimen using a Vickers indenter at 50 gm load. Subsequently, the samples were divided into six groups, which were treated for 5 minutes at 9 degrees C by a cola-based drink contacting 0, 0.5, 1, 5, and 10 wt.% of nano-HA while the control group was immersed in artificial saliva. Ultimately, the final microhardness was assessed three times again for each specimen. RESULTS: Paired t-test showed that in groups containing 0 and 0.5 wt.% of nano HA, the microhardness was significantly reduced after treatment protocol (p = 0.00 and 0.01 respectively). Whereas in the other groups the microhardness was not significantly changed after treatment (p > 0.05). CONCLUSION: Pure cola-based drink has a pronounced adverse effect on enamel microhardness, while admixing it with nano-HA could act as a protective factor. CLINICAL SIGNIFICANCE: Although soft beverages are hazardous to tooth structure, some additives could compensate their adverse effect. PMID- 27659080 TI - Work-related Musculoskeletal Pain among Different Dental Specialists in United Arab Emirates. AB - INTRODUCTION: Dentists are at a very high risk of developing work-related musculoskeletal pain. The present study aimed at studying the prevalence of musculoskeletal pain among different dental specialists in the United Arab Emirates (UAE), and correlating the region of pain with the type of clinical work done by the specialists. MATERIALS AND METHODS: A sample of more than 100 dentists was chosen randomly from different emirates in UAE. An interview questionnaire was administered regarding the number of years of experience and the presence, region, duration, and type of musculoskeletal pain they experienced. RESULTS: Musculoskeletal pain is experienced by 83.3% of periodontists, 80% of conservative dentists, 77.8% of endodon-tists, 72.7% of orthodontists, 70% of oral surgeons, 63.6% of prosthodontists, 63% of general dental practitioners, and 50% of pedodontists. The results have also indicated that the region of experienced musculoskeletal pain does vary according to the specialty. From those dentists who experience work-related musculoskeletal pain, 80% of conservative dentists experience pain in neck and shoulders, 66.7% of periodontists, and 54.5% of orthodontists experience pain in the lower back region. More than 50% of endodontists experience pain in the neck and shoulders regions, and 39% of general dental practitioners who experience pain in the neck region. CONCLUSION: Preventive measures need to be taken to decrease the risk of dentists and dental specialists developing work-related musculoskeletal pain. CLINICAL SIGNIFICANCE: The prevalence and distribution of musculoskeletal disorders (MSDs) among registered general dental practitioners and dental specialists in UAE was not clearly documented. The study results indicated that the region that experienced musculoskeletal pain does vary according to the specialty. PMID- 27659081 TI - Remineralizing Effect of Topical NovaMin and Nano-hydroxyapatite on caries-like Lesions in Primary teeth. AB - INTRODUCTION: NovaMin is a synthetic mineral compound composed of calcium, sodium, phosphorus, and silica. It releases crystalline hydroxyl-carbonate apatite (HCA), which structurally resembles the minerals naturally found in the teeth. Nano-hydroxyapatite (NHA) is a biocompatible compound with high affinity for tooth enamel. NHA particles morphologically resemble dental enamel apatite crystals. Considering the efficacy of remineralizing agents and the importance of conservative preventive measures, this study aimed to compare the remin-eralizing effects of NovaMin and NHA on caries-like lesions in primary teeth. MATERIALS AND METHODS: This in vitro experimental study was conducted on 30 sound human primary anterior teeth with no cracks or fractures. The surface microhardness (SMH) of each tooth was measured at baseline using a Vickers microhard-ness tester. The teeth were then subjected to remineralization/ demineralization cycles, and artificial caries lesions were created in them. The SMH of each tooth was measured again and the teeth were then randomly treated with toothpastes containing NovaMin or 10% NHA powder for 2 minutes daily for a period of 5 days. The SMH of each was again measured afterward. Data were statistically analyzed using independent t-tests and Mann-Whitney U tests. RESULTS: The mean SMH was found to be higher in the teeth treated with NovaMin toothpaste (422.67 kgf/mm(2)) than in the teeth treated with NHA (384.2 kgf/mm(2)); However, this difference was not statistically significant. CONCLUSION: Both NHA and NovaMin were effective for reminer-alization of caries-like lesions of primary teeth and no significant difference was detected in their efficacy. PMID- 27659082 TI - Antibacterial Activity of Leaf Extract of Annona muricata and Simarouba glauca on Enterococcus faecalis. AB - AIM: To determine the antimicrobial effect of water extracts of leaves of Annona muricata and Simarouba glauca on Enterococcus faecalis using agar diffusion method. MATERIALS AND METHODS: Dried leaves of A. muricata and S. glauca were powdered and extracted in a soxhlet apparatus. Enterococcus faecalis was grown overnight in Trypticase soy agar plates. About 10 MUl of each extract was placed on agar plates and incubated overnight. The zone of inhibition was measured after 24 hours. About 1% sodium hypochlorite and distilled water were used as positive and negative controls. RESULTS: The leaf extract of A. muricata showed similar effectiveness as that of sodium hypochlorite, whereas the leaf extract of S. glauca showed only a slight reduction in growth of E. faecalis. CONCLUSION: Leaf extract of A. muricata can be developed as an alternative to sodium hypochlorite for root canal irrigants. CLINICAL SIGNIFICANCE: Success of endodontic treatment depends on complete disinfection of the root canals. Root canal irrigants have a major role in complete disinfection of the root canals. Chemical root canal irrigants are more or less toxic to the oral environment. In this study, naturally derived leaf extracts of A. muricata and S. glauca are compared with sodium hypochlorite for its effectiveness against E. faecalis - the most common pathogen found in the root canals. PMID- 27659083 TI - Assessment of Correlation between Clinical Parameters and Pulp Canal Pathogens in Endodontic Pathologies: A Microbiological Study. AB - INTRODUCTION: Success and failure of root canal therapy is largely dependent on the clinician and the patient. Once the tooth is restored into its functional and esthetic place, the root canal therapy is considered to be complete. It is a well known fact that root canal space acts as a rich reservoir for microorganisms. Past studies show that root canal harbors an array of different microorganisms. Streptococcus mitis and Enterococcus faecalis have been found to be the most prevalent microorganisms isolated from the infected pulp canal space. Hence, we evaluated the association of endodontic signs and symptoms with root canal pathogens. MATERIALS AND METHODS: A total of 120 patients were selected for the study and divided broadly into two groups: Group I containing patients with primary infection and group II containing patients in which retreatment was required. Both groups contained 60 patients each. Clinical parameters recorded for the study are pain, tenderness on percussion, swelling, periapical radiolucency on radiographic analysis, caries, sinus formation, and tooth mobility. After assessment, opening, and initial filing, sterile paper points were inserted into the root canal space for collection of microbiological sample, which was further send to laboratory for cultural analysis. All the results were analyzed by Statistical Package for the Social Sciences (SPSS) software. Student's t-test and Fisher's exact test were used to evaluate the level of significance. RESULTS: While comparing the mean age of the patients in the two groups, no significant association was seen. Statistically significant results were obtained while comparing the association between pain and S. mitis. Positive correlation was seen on comparing the association between tenderness on percussion and E. faecalis. Also, a positive association was seen between periapical radiolucency and S. mitis. CONCLUSION: Strong positive correlation exists between S. mitis and E. faecalis and endodontic signs and symptoms. CLINICAL SIGNIFICANCE: Sound knowledge regarding the association of microbes of root canal and specific endodontic signs and symptoms could help therapeutic management of root canal infections effectively. PMID- 27659085 TI - A Comparative Study of the Retentive Strengths of Commercial and Indigenously Developed Luting Cements using Both Lathe-cut and Clinically Simulated Specimens. AB - INTRODUCTION: Superior adhesive strength in luting agents is of paramount significance in fixed partial denture success. In this in vitro study five cements were tested for retentive qualities, using both lathe-cut and hand prepared specimens. MATERIALS AND METHODS: A total of 104 freshly extracted tooth specimens were prepared. Seventy of them were lathe-cut and 30 specimens were hand-prepared to simulate clinical conditions. Five different cements were tested, which included a compomer, a composite, a zinc phosphate, and 2 glass ionomer luting cements. Of the 5, 2 trial cements were indigenously developed by Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, India - a glass-ionomer cement (Chitra GIC) and a chemical-cure composite (Chitra CCC). All cements were compared within each group and between groups (lathe-prepared and hand-prepared). RESULTS: GC Fuji 1 (GC America) exhibited superior retentive strengths in both lathe-cut and hand-prepared specimens, whereas the compomer cement displayed the lowest values when tested. In lathe-cut specimens, statistical analysis showed no significant difference between GC Fuji 1 and indigenously developed Chitra CCC. CONCLUSION: Both Chitra CCC and GC Fuji 1 have comparable strengths in lathe-cut samples, making Chitra CCC a potential luting agent. Statistical analysis reveals that all cements, except GC Fuji 1, exhibited a significant decrease in strength due to the change in design uniformity. The chemical bonding of GC Fuji 1 proves to be quite strong irrespective of shape and precision of the tooth crown. CLINICAL SIGNIFICANCE: The indigenously developed Chitra GIC and Chitra CCC showed promising results to be used as a potential luting agent. PMID- 27659084 TI - Impact of Various Irrigating Agents on Root Fracture: An in vitro Study. AB - INTRODUCTION: Irrigating solutions are used for cleaning and removing dentinal debris, and the other remains from pulpal space during biomechanical preparation. Therefore, we evaluated the impact of various irrigating agents on root fracture at 5-minute time exposure. MATERIALS AND METHODS: We sectioned 60 permanent maxillary premolars with fully formed root structures transversely maintaining the root length of approximately 14 mm. Five study groups were made comprising ethylenediaminetetraacetic acid (EDTA), cetrimide, citric acid, and so on as various irrigating agents. A universal force test machine was used to calculate the force which was enough to fracture each root. Analysis of variance (ANOVA) test was used to access the level of significance. RESULTS: About 10% citric acid solution as an irrigating agent showed minimal fracture opposing results, whereas 10% EDTA solution showed the maximum fracture resistance of root portion. CLINICAL SIGNIFICANCE: Selection of suitable EDTA concentration that has minimal adverse effect on the mechanical properties of the tooth is very important for the successful management of tooth fracture. CONCLUSION: About 10% EDTA provided the highest fracture resistance, necessitating the use of irrigating solution in root canal therapy (RCT). Further research with higher and different study groups is required to search for more efficient irrigating solution to improve the outcome of RCT. PMID- 27659086 TI - Intricate Assessment and Evaluation of Effect of Bruxism on Long-term Survival and Failure of Dental Implants: A Comparative Study. AB - INTRODUCTION: Dental implants are one of the common lines of treatment used for the treatment of missing tooth. Various risk factors are responsible for the failure of the dental implants and occurrence of postoperative complications. Bruxism is one such factor responsible for the failure of the dental implants. The actual relation between bruxism and dental implants is a subject of long-term controversy. Hence, we carried out this retrospective analysis to assess the complications occurring in dental implants in patients with and without bruxism. MATERIALS AND METHODS: The present study included 1100 patients which were treated for rehabilitation by dental implant procedure at 21 dental offices of Ghaziabad (India) from 2004 to 2014. Analyzing the clinical records of the patients along with assessing the photographs of the patients was done for confirming the diagnosis of bruxism. Clinical re-evaluation of the patients, who came back for follow-up, was done to confirm the diagnosis of bruxism. Systemic questionnaires as used by previous workers were used to evaluate the patients about the self-conscience of the condition. Estimation of the mechanical complications was done only in those cases which occurred on the surfaces of the restoration of the dental implants. All the results were analyzed by Statistical Package for Social Sciences (SPSS) software. Student's t-test and Pearson's chi square test were used to evaluate the level of significance. RESULTS: In both bruxer and non-bruxers, maximum number of dental implants was placed in anterior maxillary region. Significant difference was obtained while comparing the two groups for dimensions of the dental implants used. On comparing the total implant failed cases between bruxers and non-bruxers group, statistically significant result was obtained. Statistically significant difference was obtained while comparing the two study groups based on the health parameters, namely hypertension, diabetes, and smoking habit. CONCLUSION: Success of dental implant is significantly affected by bruxism. Special attention is required in such patients while doing treatment planning. CLINICAL SIGNIFICANCE: For the long-term clinical success and survival of dental implants in patients, special emphasis should be given on the patient's deleterious oral habits, such as bruxism as in long run, they influence the stability of dental implants. PMID- 27659088 TI - Improved Visualization and Assessment of Condylar Position in the Glenoid Fossa for Different Occlusions: A CBCT Study. AB - INTRODUCTION: The position of the condyle in the glenoid fossa plays an important role in the stability of occlusion after orthodontic treatment. Cone beam computed tomography (CBCT) provides an optimal imaging of the osseous components of the temporomandibular joint (TMJ) and give a full size truly three-dimensional (3D) description in real anatomical size. The present study aimed to visualize and compare the position of condyle in the glenoid fossa for different occlusions by using CBCT Materials and methods: Cone beam computed tomographic images of 45 subjects, aged 18 to 42 years, were evaluated. Subjects were equally divided into three groups according to the A point, nasion, B point (ANB) angle. RESULTS: In the sagittal plane, condyle is positioned nonconcen-trically; positioned anteriosuperiorly in class I and III occlusions and lies posteriosuperiorly in class II occlusion. In the frontal plane, condyle is positioned centrally (mediolaterally) in all the three types of occlusions. In the axial plane, the parameters showed significant difference between the different occlusions. No statistical significant distinction could be made in the position of the condyle when comparing the right and left joints. CONCLUSION: The position of condyle in glenoid fossa influences sagittal, transverse, and vertical relationships of the jaws which eventually contribute to development of various malocclusions. Nonconcentricity is the feature of the condyle in the sagittal plane in different malocclusions. CLINICAL SIGNIFICANCE: An important consideration in orthodontic treatment is the recognition of the importance that the dentition should be in harmony with the related musculoskeletal structures. Therefore, the condylar position is an important concern in maintaining or restoring temporomandibular harmony with the dentition and the position of the condyle in the glenoid fossa plays an important role in the stability of occlusion after orthodontic treatment. PMID- 27659087 TI - Comparative Evaluation of Pediatric Patients with Mental Retardation undergoing Dental Treatment under General Anesthesia: A Retrospective Analysis. AB - INTRODUCTION: Behavioral management of patients forms one of the foremost components of pediatric dental treatment. Some children readily cooperate with dental treatment, while others require general anesthesia as a part of treatment protocol for carrying out various dental procedures. Hence, we evaluated the pediatric patients with and without mental retardation, who underwent dental treatment under general anesthesia. MATERIALS AND METHODS: The present study analyzed the record of 480 pediatric patients reporting in the department of pedodontics from 2008 to 2014. Analysis of the records of the patients who underwent dental treatment under general anesthesia was done and all the patients were divided into two study groups depending upon their mental level. For the purpose of evaluation, the patients were also grouped according to their age; 4 to 7 years, 8 to 12 years, and 13 to 18 years. Measurement of decayed, missing, and filled teeth and scores for both deciduous and permanent dentition was done before and after the commencement of the dental treatment. Chi-square test and independent t-test were used for evaluating the level of significance. RESULTS: While comparing the patients in the two groups, maximum number of patients is present in the age group of 13 to 18 years. While comparing the indices' score between the two study groups in various age intervals, no statistically significant results were obtained. Restorative treatment and dental extractions were the most common dental treatments that were seen at a higher frequency in the intellectual disability study group. CONCLUSION: In patients with mental retardation, a higher frequency of restorative treatment and extractions occurs as compared to healthy subjects of similar age group. Therefore, they require special attention regarding maintenance of their oral health. CLINICAL SIGNIFICANCE: Special attention should be given for maintaining the oral health of patients with special health care needs as compared to their physically and mentally normal counterparts. PMID- 27659089 TI - Retrospective Analysis of Different Bracket Systems used in the Treatment of Patients with Anterior Crowding: A Longitudinal Comparative Study. AB - INTRODUCTION: New design of brackets have been introduced in the field of orthodontics in the recent past, and one of such advancement is the self-ligating brackets. These brackets are said to have less friction, with a shorter period of treatment. Better patient acceptance and good treatment results are some of the other advantages offered by self-ligating brackets. Hence, we comparatively evaluated root resorption of anterior teeth by self-ligating and conventional preadjusted brackets in cases of severe anterior crowding in class I patients. MATERIALS AND METHODS: The present study was carried out at the department of orthodontics in a dental institution and included 140 patients that presented with the chief complaint of Angle class I malocclusion with crowding of more than 6 mm in the anterior tooth region. Two groups were formed with 70 patients in each group. In one group self-ligating brackets were used, while in other group conventional brackets were used. Malmgren's method was sued for evaluating the root resorption score ranging from 0 to 4. All the results were analyzed by the Statistical Package for the Social Sciences software. Chi-square test, nonpaired t-test, and paired t-test were used to evaluate the level of significance. RESULTS: The mean age of the patients in groups I and II was 13.92 and 13.81 years respectively. While comparing age of the patients and time duration of the treatment, no significant results were obtained. While comparing the root resorptions at various time intervals in groups I and II patients, significant results were obtained. While comparing the root resorptions in between groups I and II patients, no statistically significant results were obtained (p-value > 0.05). CONCLUSION: Statistically similar amount of resorption is seen in patients in both the groups either on self-ligating brackets or on conventional preadjusted brackets during treatment of Angle class I patients with severe anterior crowding. CLINICAL SIGNIFICANCE: In treating anterior crowding patients with Angle class I patients, choice of brackets has no effect on the amount of root resorption. PMID- 27659090 TI - Evaluation of Potential Risk Factors that contribute to Malignant Transformation of Oral Lichen Planus: A Literature Review. AB - AIM: Many studies have suggested that a lesion originally diagnosed as oral lichen planus (OLP) has different possibilities of undergoing malignant transformation in time, although these findings remain a controversial issue; for example, some studies reported different values of potential malignancy of OLP. INTRODUCTION: World Health Organization (WHO) classifies OLP as a "potentially malignant disorder" with unspecified malignant transformation risk, and suggests that OLP patients should be closely monitored. Numerous studies have attempted to confirm the malignant transformation potential of OLP. REVIEW RESULTS: The Cochrane Controlled Trials Register, Medline and EMBASE databases, PubMed, Google Scholar, Ovid, Up To Date, BMJ Clinical Evidence, MD Consult, and Science Direct were searched for papers published between 1997 and 2015. The medical subject heading search terms were "lichen planus," "oral lichen planus," "erosive oral lichen planus," "dysplasia," "oral precancerous condition," "oral premalignant condition," oral cancer, oral squamous cell carcinoma (OSCC), and atrophic lichen planus. A total of 120 English language abstracts were reviewed, and 50 relevant articles identified. Because of the extensive literature on the association between OLP and SCC, we have divided the data into genetic and non-genetic factors for more accurate assessment. CONCLUSION: In this evidence base, malignant transformation ranges from 0 to 37% with a mean of 4.59%. The highest rate of malignancy was noted in erythematosus and erosive lesions. In this way, follow-up of OLP patients could be carried out more efficiently and appropriately. CLINICAL SIGNIFICANCE: Oral lichen planus is a premalignant lesion. All types of OLP in any site of oral mucosa must be monitored regularly. PMID- 27659091 TI - Trauma due to Self-aggression in Patient with Waardenburg Syndrome associated with Congenital Anomalies. AB - Waardenburg syndrome (WS) is an inherited autosomal dominant genetic disorder presenting variable penetrance and expressivity, with an estimated prevalence of 1:42,000. Clinical characteristics of WS include lateral displacement of the internal eye canthus, hyperplasia of the medial portion of the eyebrows, prominent and broad nasal base, congenital deafness, pigmentation of the iris and skin, and white forelock. A 24-year-old male patient, previously diagnosed with WS, was referred to the Special Needs Dental Clinic of Sacred Heart University, Bauru, Brazil. Parents reported that the patient was experiencing self mutilation, particularly in the oral region. He presented multiple congenital anomalies, including anophthalmia, mental retardation, low-set ears, and leg deformities. Clinical oral examination revealed hypodontia, abnormalities in dental morphology, extensive dental caries, periodontal disease, and fistulae. Extensive scars on the tongue, lips, and hands caused by self-mutilation were also observed. In accordance with his family and neurologist, full-mouth extraction under general anesthesia was performed, especially considering his severe self-aggressive behavior and the necessity to be fed with soft-food diet due to his inability to chew. After the surgical procedure, a significant reduction in the patient's irritability and gain of weight were reported in the follow-ups of 30, 60, and 180 days. PMID- 27659092 TI - A Solitary Phlebolith in the Buccal Mucosa: Report of a Rare Entity and Clinicopathologic Correlation. AB - Pathological conditions can give rise to calcifications within oral mucosa representing either a local or systemic disturbance. Inflammation, trauma, debris acting as nidus and vascular lesions have been attributed as principal causes for occurrence of calcifications within the oral mucosa. Occurrence of multiple calcified thrombi (phleboliths) is considered pathognomonic for hemangiomas and vascular malformations in the oral and maxillofacial region. Isolated occurrence of phlebolith in oral mucosa though very rare, especially without any underlying vascular lesions, can be diagnostically challenging. Either a traumatic association at that site or a hemangioma of childhood that has regressed once the individual became an adult are the possible explanations suggested for the occurrence of these unique solitary phleboliths. Histologically, an "onion-ring" like concentric lamellar fibrosis around a central core with varying amounts of calcifications and presence of minute vascular channels within or around calcified lamellae is characteristic for phlebolith. There is a high propensity for misdiagnosing solitary phlebolith located in sites like the buccal mucosa where various other pathologic soft-tissue calcifications, such as sialoliths, calcified lymph nodes, traumatic myositis ossificans, etc. can occur and they too appear radiopaque in radiographs. Besides, the absence of any associated underlying vascular lesion adds to the mispercep-tion. In such cases, histopathological examination with routine hematoxylin and eosin staining alone may not be sufficient to determine the accurate diagnosis. Allied clinical history and immunohistochemistry can aid to arrive at the final diagnosis. We report such a case of nonvascular lesion-associated solitary phlebolith in the right buccal mucosa of a healthy 49-year-old male patient and discuss its differential diagnosis with emphasis on histological presentation. PMID- 27659093 TI - Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols. AB - Mammalian survival depends on ultrasensitive olfactory detection of volatile sulfur compounds, since these compounds can signal the presence of rancid food, O2 depleted atmospheres, and predators (through carnivore excretions). Skunks exploit this sensitivity with their noxious spray. In commerce, natural and liquefied gases are odorized with t-BuSH and EtSH, respectively, as warnings. The 100-million-fold difference in olfactory perception between structurally similar EtSH and EtOH has long puzzled those studying olfaction. Mammals detect thiols and other odorants using odorant receptors (ORs), members of the family of seven transmembrane G-protein-coupled receptors (GPCRs). Understanding the regulator cofactors and response of ORs is particularly challenging due to the lack of X ray structural models. Here, we combine computational modeling and site-directed mutagenesis with saturation transfer difference (STD) NMR spectroscopy and measurements of the receptor response profiles. We find that human thiol receptor OR2T11 responds specifically to gas odorants t-BuSH and EtSH requiring ionic copper for its robust activation and that this role of copper is mimicked by ionic and nanoparticulate silver. While copper is both an essential nutrient for life and, in excess, a hallmark of various pathologies and neurodegenerative diseases, its involvement in human olfaction has not been previously demonstrated. When screened against a series of alcohols, thiols, sulfides, and metal-coordinating ligands, OR2T11 responds with enhancement by copper to the mouse semiochemical CH3SCH2SH and derivatives, to four-membered cyclic sulfide thietane and to one- to four-carbon straight- and branched-chain and five-carbon branched-chain thiols but not to longer chain thiols, suggesting compact receptor dimensions. Alcohols are unreactive. PMID- 27659094 TI - Technical aspects of transurethral plasmakinetic enucleation and resection of the prostate for benign prostatic hyperplasia. AB - : TUERP, which is based on TURP, technically has been proven to be safe and effective with reduced complication rates. Due to the lack of systematic pre clinical training, the surgery is learnt only inside the operative theatre in the majority of the Chinese medical centers. It is also known to have a steep learning curve, and very few articles have addressed the technical aspects of TUERP. MATERIAL AND METHODS: The videos of 91 cases of bipolar transurethral enucleation and resection of the prostate, which were performed by one urological surgeon in our department from August 2013 to January 2016, were retrospectively analyzed. With an extensive review of the literature and based on the summary of our experience, detailed techniques and tips for TUERP are described. RESULTS: The procedure is initiated from the enucleation of mid-lobe and progressed in a retrograde mode with the guide of the capsular plane. Along with the experience accumulated, the capability of landmark identifying and the surgical skills were improved. CONCLUSION: A steep operative learning curve may be the main obstacle to the widespread use of TUERP. Accurate identification and orientation of the landmark with good understanding of the three-dimensional structure of the prostatic fossa and the detailed technical issues of enucleating along the right capsule plane will be helpful for beginners to overcome the learning curve and gain confidence with this procedure and for experienced surgeons to further improve their surgical technique. PMID- 27659096 TI - Behavioral patterns, parity rate and natural infection analysis in anopheline species involved in the transmission of malaria in the northeastern Brazilian Amazon region. AB - The characterization of behavioral patterns allows a better understanding of the transmission dynamics and the design of more effective malaria vector control strategies. This study analyzed the behavioral patterns of the Anopheles species of the Coracao district situated in the northeast of the Brazilian Amazon region. The behavioral patterns of the anopheline species were measured based on the 36 collection sites of this district from December 2010 to November 2011. Collections of four hours for three consecutive nights each month and four 12-h collections, comprising two in the rainy season and two in the dry season, were performed. Furthermore, to infer the anthropophily and zoophily indexes, four additional four-hour collections were performed. The samples were also evaluated for parity rate and natural infectivity for Plasmodium spp. A total of 1689 anophelines were captured, comprising of nine species and two subgenera (Nyssorhynchus - six species, and Anopheles - three species). Anopheles darlingi was the most abundant and widely distributed species in the area, followed by A. braziliensis and A.marajoara. Anopheles darlingi and A. marajoara were the only species present in the four collections of 12-h, but only A. darlingi showed activity throughout night. Anopheles darlingi was the most anthropophilic species (AI=0.40), but the zoophily index was higher (ZI=0.60), revealing an eclectic and opportunistic behavior. Of the six most frequent species, A. nuneztovari s.l. was the most zoophilic species (ZI=1.00). All captured species showed predominance towards biting in outdoor environments. Anopheles darlingi and A. braziliensis showed multimodal biting peaks, whereas A. marajoara revealed a stable pattern, with the biting peak after sunset. Using the PCR technique, no anopheline was found infected with the malaria parasite. Since A. darlingi and A. marajoara are recognized as important vectors in this region, the district of Coracao may be considered as a highly potent area for transmission of malaria, therefore, the prevention and surveillance measures should be taken constantly to prevent the same. The role of A. braziliensis as malaria vector needs to be urgently investigated. PMID- 27659095 TI - The influence of natural factors on the spatio-temporal distribution of Oncomelania hupensis. AB - BACKGROUND: We analyzed the influence of natural factors, such as temperature, rainfall, vegetation and hydrology, on the spatio-temporal distribution of Oncomelania hupensis and explored the leading factors influencing these parameters. The results will provide reference methods and theoretical a basis for the schistosomiasis control. METHODS: GIS (Geographic Information System) spatial display and analysis were used to describe the spatio-temporal distribution of Oncomelania hupensis in the study area (Dongting Lake in Hunan Province) from 2004 to 2011. Correlation analysis was used to detect the natural factors associated with the spatio-temporal distribution of O. hupensis. Spatial regression analysis was used to quantitatively analyze the effects of related natural factors on the spatio-temporal distribution of snails and explore the dominant factors influencing this parameter. RESULTS: (1) Overall, the spatio temporal distribution of O. hupensis was governed by the comprehensive effects of natural factors. In the study area, the average density of living snails showed a downward trend, with the exception of a slight rebound in 2009. The density of living snails showed significant spatial clustering, and the degree of aggregation was initially weak but enhanced later. Regions with high snail density and towns with an HH distribution pattern were mostly distributed in the plain areas in the northwestern and inlet and outlet of the lake. (2) There were space-time differences in the influence of natural factors on the spatio-temporal distribution of O. hupensis. Temporally, the comprehensive influence of natural factors on snail distribution increased first and then decreased. Natural factors played an important role in snail distribution in 2005, 2006, 2010 and 2011. Spatially, it decreased from the northeast to the southwest. Snail distributions in more than 20 towns located along the Yuanshui River and on the west side of the Lishui River were less affected by natural factors, whereas relatively larger in areas around the outlet of the lake (Chenglingji) were more affected. (3) The effects of natural factors on the spatio-temporal distribution of O. hupensis were spatio-temporally heterogeneous. Rainfall, land surface temperature, NDVI, and distance from water sources all played an important role in the spatio temporal distribution of O. hupensis. In addition, due to the effects of the local geographical environment, the direction of the influences the average annual rainfall, land surface temperature, and NDVI had on the spatio-temporal distribution of O. hupensis were all spatio-temporally heterogeneous, and both the distance from water sources and the history of snail distribution always had positive effects on the distribution O. hupensis, but the direction of the influence was spatio-temporally heterogeneous. (4) Of all the natural factors, the leading factors influencing the spatio-temporal distribution of O. hupensis were rainfall and vegetation (NDVI), and the primary factor alternated between these two. The leading role of rainfall decreased year by year, while that of vegetation (NDVI) increased from 2004 to 2011. CONCLUSIONS: The spatio-temporal distribution of O. hupensis was significantly influenced by natural factors, and the influences were heterogeneous across space and time. Additionally, the variation in the spatial-temporal distribution of O. hupensis was mainly affected by rainfall and vegetation. PMID- 27659098 TI - Prevalence of Elevated Lp(a) Mass Levels and Patient Thresholds in 532 359 Patients in the United States. AB - OBJECTIVE: Elevated lipoprotein(a) [Lp(a)] is a causal, independent risk factor for cardiovascular disease and aortic stenosis. We aimed to define the prevalence and patient thresholds of elevated Lp(a) levels in the United States. APPROACH AND RESULTS: We analyzed Lp(a) levels in 532 359 subjects from 2 data sets: (1) in 531 144 subjects from a referral laboratory and (2) in 915 patients from a tertiary referral center. Lp(a) mass levels were measured by immunoturbidometric assays in both centers and expressed as mg/dL. At the referral laboratory, the median age (interquartile range) of the subjects was 57.0 (46-67) years, and 51.9% were female. Lp(a) levels were skewed rightward as expected. The mean+/-SD levels were 34.0+/-40.0 mg/dL, and median (interquartile range) levels were 17 (7 47) mg/dL, with range 0 to 907 mg/dL. Lp(a) levels at 75%, 80%, 90%, 95%, 99%, and 99.9% percentiles were >47, >60, >90, >116, >180, and >245 mg/dL, respectively. At the referral laboratory, Lp(a) levels >30 and >50 mg/dL were present in 35.0% and 24.0% of subjects, respectively, and at the tertiary referral center, 39.5% and 29.2%, respectively. Females had higher mean (SD) (37.0 [42.7] versus 30.7 [36.7]; P<0.0001) and median (interquartile range) (19 [8-53] versus 15 [7-42]; P<0.0001) Lp(a) than males. CONCLUSIONS: This is the largest database to assess the distribution of Lp(a) and is derived from patients as opposed to general populations. Lp(a) levels >30 and >50 mg/dL were fairly common, particularly in a tertiary care setting. These data may inform consensus documents, guidelines, and therapeutic cutoffs for Lp(a)-mediated cardiovascular risk. PMID- 27659099 TI - Aortic Elastic Properties in Preschool Children Born Preterm. AB - OBJECTIVE: Preterm birth predisposes children to the development of cardiovascular diseases in adulthood. The aim of this study was to characterize elastic properties of the aorta at preschool age and test the hypothesis that prematurity is associated with decreased aortic distensibility and increased stiffness, both of which are predictors of increased cardiovascular risk. APPROACH AND RESULTS: In an observational study of 76 five- to seven-year-old children born at a gestational age <32 weeks and 79 term-born controls, elastic parameters of the ascending and descending abdominal aorta were determined noninvasively by means of M mode echocardiographic tracings and calculated using computerized wall contour analysis. Compared with children born at term, the preterm group showed significantly reduced distensibility and increased stiffness of the descending abdominal aorta. These results remained significant under multivariable adjustment for birth weight z score, maternal smoking in pregnancy, maternal education, family history of cardiovascular disease, breastfeeding, childhood nutrition, and current body mass index z score (multivariable odds ratios and 95% confidence intervals 5.1, 1.7-15.9; P=0.005 and 2.8, 1.0-7.9; P=0.046, respectively). Further adjustment for intravenous lipid therapy attenuated the strength of association. Elastic properties of the ascending aorta did not differ between the 2 study groups. CONCLUSIONS: Children born preterm are characterized by decreased elastic properties of the descending abdominal aorta potentially attributable to impaired viscoelastic properties of and lipid damage to the aorta. Clinical follow-up of preterm infants with a focus on aortic elastic properties may be useful for tailoring early prevention programs and counteracting cardiovascular risk in adulthood. PMID- 27659097 TI - Pharmacological Targeting of Plasminogen Activator Inhibitor-1 Decreases Vascular Smooth Muscle Cell Migration and Neointima Formation. AB - OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor that promotes and inhibits cell migration, plays a complex and important role in adverse vascular remodeling. Little is known about the effects of pharmacological PAI-1 inhibitors, an emerging drug class, on migration of vascular smooth muscle cells (SMCs) and endothelial cells (ECs), crucial mediators of vascular remodeling. We investigated the effects of PAI-039 (tiplaxtinin), a specific PAI 1 inhibitor, on SMC and EC migration in vitro and vascular remodeling in vivo. APPROACH AND RESULTS: PAI-039 inhibited SMC migration through collagen gels, including those supplemented with vitronectin and other extracellular matrix proteins, but did not inhibit migration of PAI-1-deficient SMCs, suggesting that its antimigratory effects were PAI-1-specific and physiologically relevant. However, PAI-039 did not inhibit EC migration. PAI-039 inhibited phosphorylation and nuclear translocation of signal transducers and activators of transcription-1 in SMCs, but had no discernable effect on signal transducer and activator of transcription-1 signaling in ECs. Expression of low-density lipoprotein receptor related protein 1, a motogenic PAI-1 receptor that activates Janus kinase/signal transducers and activators of transcription-1 signaling, was markedly lower in ECs than in SMCs. Notably, PAI-039 significantly inhibited intimal hyperplasia and inflammation in murine models of adverse vascular remodeling, but did not adversely affect re-endothelialization after endothelium-denuding mechanical vascular injury. CONCLUSIONS: PAI-039 inhibits SMC migration and intimal hyperplasia, while having no inhibitory effect on ECs, which seems to be because of differences in PAI-1-dependent low-density lipoprotein receptor-related protein 1/Janus kinase/signal transducer and activator of transcription-1 signaling between SMCs and ECs. These findings suggest that PAI-1 may be an important therapeutic target in obstructive vascular diseases characterized by neointimal hyperplasia. PMID- 27659100 TI - Cesarean section: the pediatricians' views. AB - Cesarean sections (CS) have greatly increased and many reasons are often evoked. Safer anesthetics and surgical procedures have rendered CS a popular choice for both professionals and mothers alike. CS on maternal request, for nonmedical reasons, is the subject of scientific, legal and ethical dispute. We shall address the CS issues, primarily, from the pediatrician's point of view. The immediate neonatal problems of the more mature neonate are well recognized. For preterm birth, contradictory results on mid- and long-term outcomes do not confirm the earlier reports on neonatal advantages of CS over vaginal delivery; therefore, their mode of delivery should be based on individual circumstances. The intestinal flora of neonates delivered by CS is often deprived of the normal colonization by maternal vulvovaginal and rectal flora. Whether this adverse microbiome will play a role in the late development of multiple morbidities in children and adults is an interesting possibility open to consideration. The consequences of unnecessary CS demands a reflection for all the involved parties and the decision to perform a CS shall, then, be based on the net clinical benefit to all: the mother, the child and the future adult. PMID- 27659101 TI - Beta-blocker therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: Are all beta-blockers equivalent? PMID- 27659103 TI - Serum uric acid levels and the risk of flares among gout patients in a US managed care setting. AB - OBJECTIVE: Serum uric acid (sUA) levels are causally associated with the risk of gout flares. Our aim was to assess the magnitude of the association and time to first flare among patients in a managed care setting. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using administrative claims data from a large US health plan. Patients were required to have evidence of gout based on medical and pharmacy claims between January 2009 and April 2012. The 12 months prior to the index gout claim were used to assess baseline sUA levels; risk of gout flares, stratified by baseline sUA levels, was examined for 2 years post-index. Risk of flare was modeled with Cox proportional hazards; time to first flare was assessed by Kaplan-Meier. RESULTS: We identified 18,008 patients with gout and available baseline SUA levels (mg/dL). The hazard ratios for the risk of gout flares compared with sUA <5.0 were: 1.17 for sUA 5.0 to <6.0; 1.69 for sUA 6.0 to <7.0; 2.16 for sUA 7.0 to <8.0; 2.87 for sUA 8.0 to <9.0; and 3.85 for sUA >=9.0 (all p < .001 except for sUA 5.0 to <6.0 cohort). The time to first flare was shorter for cohorts with higher baseline sUA levels. CONCLUSION: These findings confirm that higher sUA levels are associated with an increased risk of gout flares in a dose-response manner over 2 years. This data supports the need to treat to sUA target levels as recommended by recent gout care guidelines. Claims-based algorithms were used to identify gout flares; although this would not be expected to influence estimates of risk by sUA level, there may have been over- or under-estimation of the incidence of flares. PMID- 27659104 TI - Spontaneous rupture of a liver hemangioma. A case report. AB - Spontaneous rupture of a liver hemangioma is a very uncommon disease, but extremely seriousness because it is associated to a 75% of mortality caused by hipovolemic shock. A case of an spontaneous rupture of liver hemangioma, which was previously unknow, is presented. PMID- 27659102 TI - Short time effect of a self-referral to inpatient treatment for patients with severe mental disorders: a randomized controlled trial. AB - BACKGROUND: Service user participation is a central principle in mental healthcare, and the opportunity to self-refer to inpatient treatment is used to increase service user involvement and activation. The aim of this study was to investigate the short-term effect of a self-referral system in an inpatient rehabilitation unit at a community mental health center on patient activation and recovery in individuals with severe mental disorders. METHODS: A randomized controlled study including 53 patients (41 % females, mean age 40 years). Twenty six patients in the intervention group were given a contract for self-referral to inpatient treatment, limited to maximum 5 days and a quarantine time of 14 days between each stay. The control group (27 participants) received treatment as usual, and was offered the intervention after 1 year. The Patient Activation Measure was the primary outcome and secondary outcome was the Recovery Assessment Scale. Mixed models were used to assess group differences. RESULTS: During the 4 months period, 15 (58 %) of 26 participants in the intervention group used the contract of self-referral to inpatient treatment. The intervention group had more admissions than the control group but both groups had a similar total use of inpatient days and out-patient consultations. The self-referral to inpatient treatment counted for 11 % of all inpatient days for the intervention group. There were no significant differences in the outcome between the groups on patient activation (estimated mean difference 2.7, 95 % confidence interval = 5.5 to 10.8, p = 0.52) or recovery (estimated mean difference 0.01, 95 % confidence interval = -0.3 to 0.3, p = 0.92). CONCLUSIONS: Giving persons with severe mental disorders the possibility to self-refer to inpatient treatment did not change their level of patient activation and recovery after 4 months and did not lead to increased use of health services. The cost-effectiveness and long term effect of self-referral to inpatient treatment should be investigated further. TRIAL REGISTRATION: NCT01133587 , clinicaltrials.gov. PMID- 27659105 TI - Small bowel mesenchymal tumors: description of two unusual cases. AB - We present two cases of intestinal ileal GIST who developed complications of nonspecific signs and required to be operated urgently, providing unusual images of tumors because of its characteristics. PMID- 27659106 TI - A rare presentation of gallstones: Bouveret's syndrome, a case report. AB - CT images and endoscopic findings in a case of Bouveret's syndrome. PMID- 27659108 TI - Inflammation at the blood-brain barrier: The role of liver X receptors. AB - The blood-brain barrier (BBB) is indispensable for the maintenance of brain homeostasis and proper neuronal functioning. Dysfunction of the BBB significantly contributes to the pathogenesis of neuroinflammatory and neurodegenerative diseases like stroke, multiple sclerosis (MS), and Alzheimer's disease (AD). The neuroinflammatory environment that characterizes these disorders propagates chronic impaired function of the BBB, processes that will be discussed in this review. Limiting dysfunction of the BBB may be an attractive target for treatment of neurological disorders. To date, no current treatments are directly targeting the function of the BBB. In this review, we will specifically discuss the potential protective role of nuclear liver X receptors (LXRs) as a promising therapeutic target to reverse or prevent BBB impairment in neurological diseases. PMID- 27659109 TI - Impaired bidirectional NMDA receptor dependent synaptic plasticity in the dentate gyrus of adult female Fmr1 heterozygous knockout mice. AB - Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits. We, and others, have recently reported that there is significant impairment in N-methyl-d aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal dentate gyrus (DG) of male Fmr1 knock out mice. Here we examined if female mice displaying a heterozygous loss of the Fmr1 gene (Fmr1+/-) would exhibit similar impairments in DG-dependent spatial memory processing and NMDAR hypofunction. We found that Female Fmr1+/- mice did not show impaired metabotropic glutamate receptor (mGluR)-LTD in the CA1 region, and could perform well on a temporal ordering task that is thought to involve this brain region. In contrast, female Fmr1+/- mice showed impairments in a pattern separation task thought to involve the DG, and also displayed a significant impairment in both NMDAR-dependent LTD and LTP in this region. The LTP impairment could be rescued by administering the NMDAR co-agonist, glycine. Our data suggests that NMDAR hypofunction in the DG may partly contribute to learning and memory impairment in female Fmr1+/- mice. Targeting NMDAR-dependent mechanisms may offer hope as a new therapeutic approach for treating female FXS patients with learning and memory impairments. PMID- 27659107 TI - Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice. AB - Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models. To further characterize the mechanism of TH-induced brain protection, we examined the effect of TH (at +/-33 degrees C for 6h) induced by the NTR1 agonist HPI-201 or physical (ice/cold air) cooling on inflammatory responses after ischemic stroke in mice and oxygen glucose deprivation (OGD) in cortical neuronal cultures. Seven days after focal cortical ischemia, microglia activation in the penumbra reached a peak level, which was significantly attenuated by TH treatments commenced 30min after stroke. The TH treatment decreased the expression of M1 type reactive factors including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL 1beta), IL-12, IL-23, and inducible nitric oxide synthase (iNOS) measured by RT PCR and Western blot analyses. Meanwhile, TH treatments increased the expression of M2 type reactive factors including IL-10, Fizz1, Ym1, and arginase-1. In the ischemic brain and in cortical neuronal/BV2 microglia cultures subjected to OGD, TH attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), two key chemokines in the regulation of microglia activation and infiltration. Consistently, physical cooling during OGD significantly decreased microglia migration 16h after OGD. Finally, TH improved functional recovery at 1, 3, and 7days after stroke. This study reveals the first evidence for hypothermia mediated regulation on inflammatory factor expression, microglia polarization, migration and indicates that the anti-inflammatory effect is an important mechanism underlying the brain protective effects of a TH therapy. PMID- 27659111 TI - Selected GRIN2A mutations in melanoma cause oncogenic effects that can be modulated by extracellular glutamate. AB - GRIN2A mutations are frequent in melanoma tumours but their role in disease is not well understood. GRIN2A encodes a modulatory subunit of the N-methyl-d aspartate receptor (NMDAR). We hypothesized that certain GRIN2A mutations increase NMDAR function and support melanoma growth through oncogenic effects. This hypothesis was tested using 19 low-passage melanoma cell lines, four of which carried novel missense mutations in GRIN2A that we previously reported. We examined NMDAR expression, function of a calcium ion (Ca2+) channel and its contribution to cell growth using pharmacological modulators; findings were correlated with the presence or absence of GRIN2A mutations. We found that NMDAR expression was low in all melanoma cell lines, independent of GRIN2A mutations. In keeping with this, NMDAR-mediated Ca2+ influx and its contribution to cell proliferation were weak in most cell lines. However, certain GRIN2A mutations and culture media with lower glutamate levels enhanced NMDAR effects on cell growth and invasion. The main finding was that G762E was associated with higher glutamate-mediated Ca2+ influx and stronger NMDAR contribution to cell proliferation, compared with wild-type GRIN2A and other GRIN2A mutations. The pro invasive phenotype of mutated cell lines was increased in culture medium containing less glutamate, implying environmental modulation of mutation effects. In conclusion, NMDAR ion channel function is low in cultured melanoma cells but supports cell proliferation and invasion. Selected GRIN2A mutations, such as G762E, are associated with oncogenic consequences that can be modulated by extracellular glutamate. Primary cultures may be better suited to determine the role of the NMDAR in melanoma in vivo. PMID- 27659112 TI - Bibliometric assessment of scientific production of literature of West Nile Virus. PMID- 27659113 TI - Assessment of picture archiving and communication system (PACS) at three of ministry of health hospitals in Riyadh region - Content analysis. AB - BACKGROUND: Picture archiving and communication system (PACS) are management information systems used for distributing, viewing and archiving digital images by integrating different types of modalities through communication networks. PACS have many advantages that can lead to improving health care quality. PACS has been widely used in hospitals in Saudi Arabia for the past 10 years. However, an extensive review of literature in the field of PACS, among physicians and radiologists in Saudi Arabia, showed lack of local studies of this costly and newly implemented technology. Therefore, this assessment is very important to provide an insightful study of PACS in Saudi Arabia to provide proper recommendations for the PACS projects implementation nationwide. OBJECTIVES: The objectives of this study are to, firstly, assess the perceived benefits of PACS among physicians and radiologists specifically in quality of care, secondly, assess the perceived challenges of PACS implementation and adoption inside and outside the radiology department, and thirdly, to compare between physicians' and radiologists' perceptions toward PACS. METHODS: A cross-sectional descriptive study at three of Ministry of Health (MOH) Hospitals in the Riyadh region, Saudi Arabia. The researchers used two separate surveys questionnaires, for administration to the physicians and radiologists at the three hospitals. Apart from the questionnaire, included is feedback as responses to open-ended questions. Content analysis was used to analyze the feedback under two themes: benefits or challenges. RESULTS: The response rate was 46% (84/183) physicians and 88% (15/17) radiologists have participated in this study. The result showed that 70% physicians' views affirms that PACS improved physicians' efficiency. On the other hand, all radiologists who responded affirmed that PACS improved efficiency. For questions on the ability to make decisions, 69% of views have affirmed that PACS improved physician's abilities to make decisions regarding patient care. Using PACS has led to a reduction in patients' length of stay in hospital (LOS) question, 79% of total views were positive. In contrast, only 18% of physicians talked about PACS positively in summary views and 82% talked about the challenges of PACS whereas 20% of radiologists talked about PACS positively. CONCLUSIONS: The results in the present study conclude that PACS was well perceived due to its numerous benefits among physicians and radiologists. However, radiologists showed more focus on the benefits of PACS than physicians. The main disadvantages are that PACS has resulted in difficulty in finding images, recurrent downtime and insufficient training. PMID- 27659110 TI - Acute hyperglycemia suppresses left ventricular diastolic function and inhibits autophagic flux in mice under prohypertrophic stimulation. AB - BACKGROUND: Left ventricular (LV) dysfunction is closely associated with LV hypertrophy or diabetes, as well as insufficient autophagic flux. Acute or chronic hyperglycemia is a prognostic factor for patients with myocardial infarction. However, the effect of acute hyperglycemia on LV dysfunction of the hypertrophic heart and the mechanisms involved are still unclear. This study aimed to confirm our hypothesis that either acute or chronic hyperglycemia suppresses LV diastolic function and autophagic flux. METHODS: The transverse aortic constriction (TAC) model and streptozocin-induced type 1 diabetic mellitus mice were used. LV function was evaluated with a Millar catheter. Autophagic levels and autophagic flux in the whole heart and cultured neonatal rat cardiomyocytes in response to hyperglycemia were examined by using western blotting of LC3B-II and P62. We also examined the effect of an autophagic inhibitor on LC3B-II and P62 protein expression and LC3 puncta. RESULTS: In mice with TAC, we detected diastolic dysfunction as early as 30 min after TAC. This dysfunction was indicated by a greater LV end-diastolic pressure and the exponential time constant of LV relaxation, as well as a smaller maximum descending rate of LV pressure in comparison with sham group. Similar results were also obtained in mice with TAC for 2 weeks, in addition to increased insulin resistance. Acute hyperglycemic stress suppressed diastolic function in mice with myocardial hypertrophy, as evaluated by invasive LV hemodynamic monitoring. Mice with chronic hyperglycemia induced by streptozocin showed myocardial fibrosis and diastolic dysfunction. In high glucose-treated cardiomyocytes and streptozocin treated mice, peroxisome proliferator-activated receptor-gamma coactivator 1alpha was downregulated, while P62 was upregulated. Autophagic flux was also significantly inhibited in response to high glucose exposure in angiotensin-II treated cardiomyocytes. CONCLUSIONS: Acute hyperglycemia suppresses diastolic function, damages mitochondrial energy signaling, and inhibits autophagic flux in prohypertrophic factor-stimulated cardiomyocytes. PMID- 27659114 TI - Vaccination adherence: Review and proposed model. AB - BACKGROUND: The prevalence of childhood vaccine-preventable diseases can be significantly reduced through adherence to confirmed vaccination schedules. However, many barriers to vaccination compliance exist, including a lack of awareness regarding the importance of vaccines, missing due dates, and fear of complications from vaccinations. The aim of this study is to review the existing tools and publications regarding vaccination adherence, and to propose a design for a vaccination adherence application (app) for smartphones. METHODS: Android and iOS apps designed for vaccination reminders have been reviewed to examine six elements: educational factor; customizing features; reminder tools; peer education facilitations; feedback, and the language of apps' interface and content. The literature from PubMed has been reviewed for studies addressing reminder systems or tools including apps. RESULTS: The study has revealed insufficient (n=6) technology-based interventions for increasing childhood vaccination rates by reminding parents in comparison to the fast growth in technology, out of which are two publications discussed mobile apps. Ten apps have been found in apps stores; only one out of them was designed for the Saudi vaccination schedule in Arabic language with some weaknesses. The study proposed a design for a vaccination reminder app that includes a number of features in order to overcome the limitations discussed in the studied reminders, apps, and systems. The design supports the Arabic language and the Saudi vaccination schedule; parental education including peer education; a variety of reminder methods, and the capability to track vaccinations and refer to the app as a personal health record. CONCLUSION: The study discussed a design for a vaccination reminder app that satisfies the specific requirements for better compliance to children's immunization schedules based on reviewing the existing apps and publications. The proposed design includes element to educate parents and answer their concerns about vaccines. It involves their peers and can encourage the exchange of experiences and overcome vaccine fears. In addition, it could form a convenient child personal health record. PMID- 27659115 TI - The influence of system quality characteristics on health care providers' performance: Empirical evidence from Malaysia. AB - BACKGROUND: The Ministry of Health Malaysia initiated the total hospital information system (THIS) as the first national electronic health record system for use in selected public hospitals across the country. Since its implementation 15 years ago, there has been the critical requirement for a systematic evaluation to assess its effectiveness in coping with the current system, task complexity, and rapid technological changes. The study aims to assess system quality factors to predict the performance of electronic health in a single public hospital in Malaysia. METHODS: Non-probability sampling was employed for data collection among selected providers in a single hospital for two months. Data cleaning and bias checking were performed before final analysis in partial least squares structural equation modeling. RESULTS AND CONCLUSIONS: Convergent and discriminant validity assessments were satisfied the required criterions in the reflective measurement model. The structural model output revealed that the proposed adequate infrastructure, system interoperability, security control, and system compatibility were the significant predictors, where system compatibility became the most critical characteristic to influence an individual health care provider's performance. The previous DeLone and McLean information system success models should be extended to incorporate these technological factors in the medical system research domain to examine the effectiveness of modern electronic health record systems. In this study, care providers' performance was expected when the system usage fits with patients' needs that eventually increased their productivity. PMID- 27659116 TI - Neurofeedback Training Effects on Inhibitory Brain Activation in ADHD: A Matter of Learning? AB - Neurofeedback training (NF) is a promising non-pharmacological treatment for ADHD that has been associated with improvement of attention-deficit/hyperactivity disorder (ADHD)-related symptoms as well as changes in electrophysiological measures. However, the functional localization of neural changes following NF compared to an active control condition, and of successful learning during training (considered to be the critical mechanism for improvement), remains largely unstudied. Children with ADHD (N=16, mean age: 11.81, SD: 1.47) were randomly assigned to either slow cortical potential (SCP, n=8) based NF or biofeedback control training (electromyogram feedback, n=8) and performed a combined Flanker/NoGo task pre- and post-training. Effects of NF, compared to the active control, and of learning in transfer trials (approximating successful transfer to everyday life) were examined with respect to clinical outcome and functional magnetic resonance imaging (fMRI) changes during inhibitory control. After 20 sessions of training, children in the NF group presented reduced ADHD symptoms and increased activation in areas associated with inhibitory control compared to baseline. Subjects who were successful learners (n=9) also showed increased activation in an extensive inhibitory network irrespective of the type of training. Activation increased in an extensive inhibitory network following NF training, and following successful learning through NF and control biofeedback. Although this study was only powered to detect large effects and clearly requires replication in larger samples, the results suggest a crucial role for learning effects in biofeedback trainings. PMID- 27659117 TI - Structural connectivity within neural ganglia: A default small-world network. AB - Diffusion tensor imaging (DTI) provides a unique contrast based on the restricted directionality of water movement in an anisotropic environment. As such, DTI based tractography can be used to characterize and quantify the structural connectivity within neural tissue. Here, DTI-based connectivity within isolated abdominal ganglia of Aplysia californica (ABG) is analyzed using network theory. In addition to quantifying the regional physical proprieties of the fractional anisotropy and apparent diffusion coefficient, DTI tractography was used to probe inner-connections of local communities, yielding unweighted, undirected graphs that represent community structures. Local and global efficiency, characteristic path lengths and clustering analysis are performed on both experimental and simulated data. The relevant intensity by which these specific nodes communicate is probed through weighted clustering coefficient measurements. Both small worldness and novel small-world metrics were used as tools to verify the small world properties for the experimental results. The aim of this manuscript is to categorize the properties exhibited by structural networks in a model neural tissue to derive unique mean field information that quantitatively describe macroscopic connectivity. For ABG, findings demonstrate a default structural network with preferential specific small-world properties when compared to simulated lattice and random networks that are equivalent in order and degree. PMID- 27659119 TI - Anti-inflammatory, Analgesic and Anti-ulcerogenic Activities of Novel bis thiadiazoles, bis-thiazoles and bis-formazanes. AB - BACKGROUND: Indane-1,3-dione, thiazole, bis-thiazole and thiadiazoles rings are very interested moieties in anti-inflammatory and analgesic drugs. OBJECTIVE: The goal of this work is to synthesize new derivatives of bis-thiazoles and bis-1,3,4 thiadiazoles for the investigation of their anti-inflammatory, anti-ulcerogenic and analgesic activities. METHODS: 1,1'-(1,2-phenylene)bis(3-phenylthiourea) (1) reacts with a number of N-aryl arenecarbohydrazonoyl chlorides 2 to give a series of new bis-1,3,4-thiadiazoles 4. Also, reaction of bisthiosemicarbazone of 1,3 indanedione 6 with another type of hydrazonoyl halides namely, N-aryl-2- oxapropanehydrazonoyl chlorides 7 and ethyl-(N-arylhydrazono)chloroacetate 8 in dioxane under reflux in the presence of triethylamine give the respective bis thiazole derivatives 9 and 10, respectively. The products 9 and 10 can exist in five and seven tautomeric forms for each one. Their actual tautomeric forms were deduced based on electronic absorption data (UV / Vis spectra). Moreover, a series of novel bis-formazans 12 and 13 have been synthesized by reaction of 1,3 dihydrazono-2,3- dihydro-1H-indene (11) with both hydrazonoyl chlorides 7 and 8. RESULTS: The structure of all the novel products was deduced by elemental analysis and spectral data. In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, anti-ulcerogenic and analgesic agents. CONCLUSION: In this context, we synthesize new derivatives of bis-thiazoles and bis-1,3,4 thiadiazoles as anti-inflammatory, anti-ulcerogenic and analgesic agents. PMID- 27659118 TI - When the Brain Takes 'BOLD' Steps: Real-Time fMRI Neurofeedback Can Further Enhance the Ability to Gradually Self-regulate Regional Brain Activation. AB - Brain-computer interfaces (BCIs) based on real-time functional magnetic resonance imaging (rtfMRI) are currently explored in the context of developing alternative (motor-independent) communication and control means for the severely disabled. In such BCI systems, the user encodes a particular intention (e.g., an answer to a question or an intended action) by evoking specific mental activity resulting in a distinct brain state that can be decoded from fMRI activation. One goal in this context is to increase the degrees of freedom in encoding different intentions, i.e., to allow the BCI user to choose from as many options as possible. Recently, the ability to voluntarily modulate spatial and/or temporal blood oxygenation level-dependent (BOLD)-signal features has been explored implementing different mental tasks and/or different encoding time intervals, respectively. Our two session fMRI feasibility study systematically investigated for the first time the possibility of using magnitudinal BOLD-signal features for intention encoding. Particularly, in our novel paradigm, participants (n=10) were asked to alternately self-regulate their regional brain-activation level to 30%, 60% or 90% of their maximal capacity by applying a selected activation strategy (i.e., performing a mental task, e.g., inner speech) and modulation strategies (e.g., using different speech rates) suggested by the experimenters. In a second step, we tested the hypothesis that the additional availability of feedback information on the current BOLD-signal level within a region of interest improves the gradual self regulation performance. Therefore, participants were provided with neurofeedback in one of the two fMRI sessions. Our results show that the majority of the participants were able to gradually self-regulate regional brain activation to at least two different target levels even in the absence of neurofeedback. When provided with continuous feedback on their current BOLD signal level, most participants further enhanced their gradual self-regulation ability. Our findings were observed across a wide variety of mental tasks and across clinical MR field strengths (i.e., at 1.5T and 3T), indicating that these findings are robust and can be generalized across mental tasks and scanner types. The suggested novel parametric activation paradigm enriches the spectrum of current rtfMRI-neurofeedback and BCI methodology and has considerable potential for fundamental and clinical neuroscience applications. PMID- 27659120 TI - In vivo emergence of rifampicin resistance by rpoB mutation in Listeria monocytogenes during therapy of prosthetic joint infection. PMID- 27659121 TI - Institute of Medicine Measures of Social and Behavioral Determinants of Health: A Feasibility Study. AB - INTRODUCTION: Social and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order. METHODS: Adults, aged >=18 years, were recruited using ResearchMatch.org for this randomized, parallel design study conducted in 2015 (data analyzed in 2015-2016). Three versions of the SBD measures, sharing the same items but in different orders of presentation (Versions 1-3), were developed. Randomized to six groups, participants completed each version at least 1 week apart (Weeks 1-3). Version order was counterbalanced across each administration and randomization was stratified by gender, race, and age. Main outcomes were effect of question order, completion time, and non-response rates. RESULTS: Of 781 participants, 624 (80%) completed the Week 1 questionnaire; median completion time for answering all SBD questions was 5 minutes, 583/624 participants answered all items, and no statistically significant differences associated with question order were observed when comparing responses across all versions. No significant differences in responses within assignment groups over time were found, with the exception of the stress measure for Group 5 (p=0.036). CONCLUSION: Question order did not significantly impact participant responses. Time to complete the questionnaire was brief, and non-response rate was low. Findings support the feasibility of using the Institute of Medicine-recommended questionnaire to capture SBDs. PMID- 27659122 TI - Challenges in Assessing Mobile Health App Quality: A Systematic Review of Prevalent and Innovative Methods. AB - CONTEXT: Mobile apps are poised to become a major source of health guidance; however, concerns about their quality and safety remain. Governments, clinicians, and health researchers are struggling to determine how to adequately evaluate the content and function of mobile health apps to guide consumers toward apps that will effectively and safely support their health. Researchers are both adapting existing research methods, such as those for systematic reviews, and exploring novel methods toward this aim. The purpose of this systematic review was to describe prevalent and emerging methods for searching, data extraction, and analysis in the context of mobile health apps and commercial app stores. EVIDENCE ACQUISITION: A systematic search was conducted on April 6, 2016, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, for published studies that evaluated health-related apps targeted at consumers in a commercial app store, and a descriptive content analysis of their methods was performed. EVIDENCE SYNTHESIS: Although the majority of studies self-identified as "reviews" or "systematic reviews," their claims to have performed an exhaustive, replicable, and systematic search and data extraction are unsupported, given the nature of commercial app stores' search engines and personalized app content. Currently, studies of health-related app content are largely descriptive, and most use surrogate and one-dimensional outcome measures for app content quality. CONCLUSIONS: This field is rapidly developing, and innovative methods for systematic searches, multidimensional quality assessment, and contextualizing content assessment are emerging. Areas for future methodologic development are highlighted, including expanding definitions of app "content" and assessing risk of bias. PMID- 27659123 TI - States' Influences on Medicaid Investments to Address Patients' Social Needs. AB - INTRODUCTION: Relationships between socioeconomic adversity and poor health have been well documented. Given these associations, Medicaid MCOs (MMCOs) have shown increasing interest in addressing social determinants of health (SDH) to improve health and decrease healthcare costs. The authors sought to better understand how contractual relationships with State Medicaid Agencies influence MMCO investments in addressing members' SDH. METHODS: In 52 semi-structured key informant interviews, MMCO executives representing 17 geographically diverse MMCOs ranging in size, commercial status, and state participation in Medicaid expansion were asked to describe existing state and other influences on MMCO SDH-related activities. The authors followed an established iterative coding, thematic development, and interpretation process to analyze all interview transcripts. All data were collected and analyzed between November 2014 and November 2015. RESULTS: Informants highlighted both general and state-specific regulations that limit MMCOs from incorporating SDH-oriented solutions into care delivery, including regulations governing claimable expenses, rate determination, and enrollment eligibility. MMCO leaders also made recommendations to State Medicaid Agencies to help overcome perceived barriers. CONCLUSIONS: MMCO experiences should inform new strategies to sustainably implement SDH innovations. An initial promise of managed care was that an MMCO that improves member health through cost efficient innovations would benefit financially. The views expressed in these interviews challenge this framework's suitability for promoting SDH innovations, as many SDH-promoting services may instead translate into financial losses for MMCOs, even as they produce positive impacts on members' health. PMID- 27659124 TI - Talking to the neighbours: The molecular and physiological mechanisms of clustered synaptic plasticity. AB - Synaptic connectivity forms the basis for neuronal communication and the storage of information. Experiences and learning of new abilities can drive remodelling of this connectivity and promotes the formation of spine clusters; dendritic segments with a higher spine density. Spines located within these segments are frequently co-activated, undergo different dynamics than synapses located outside of this dendritic compartment and have, in general, a longer lifetime. Several lines of evidence have shown that chemical synapses located close to each other share or compete for intracellular signalling molecules and structural resources. This sharing and competition directly influences spine dynamics. Spines can grow, shrink, increase or decrease the surface expression of receptors, channels and adhesion molecules or remain stable and unchanged over extended periods of time. Here we summarize recent discoveries and provide a closer look at spine clustering, dendritic segment-specific signalling and potential molecular mechanisms underlying associative and heterosynaptic plasticity. PMID- 27659125 TI - The potential for animal models to provide insight into mild traumatic brain injury: Translational challenges and strategies. AB - Mild traumatic brain injury (mTBI) is a common health problem. There is tremendous variability and heterogeneity in human mTBI, including mechanisms of injury, biomechanical forces, injury severity, spatial and temporal pathophysiology, genetic factors, pre-injury vulnerability and resilience factors, and clinical outcomes. Animal models greatly reduce this variability and heterogeneity, and provide a means to study mTBI in a rigorous, controlled, and efficient manner. Rodent models, in particular, are time- and cost-efficient, and they allow researchers to measure morphological, cellular, molecular, and behavioral variables in a single study. However, inter-species differences in anatomy, morphology, metabolism, neurobiology, and lifespan create translational challenges. Although the term "mild" TBI is used often in the pre-clinical literature, clearly defined criteria for mild, moderate, and severe TBI in animal models have not been agreed upon. In this review, we introduce current issues facing the mTBI field, summarize the available research methodologies and previous studies in mTBI animal models, and discuss how a translational research approach may be useful in advancing our understanding and management of mTBI. PMID- 27659127 TI - Fibroblast growth factor 23 actions in inflammation: a key factor in CKD outcomes. AB - During chronic kidney disease (CKD), bone mineral metabolism is disturbed owing in part to the endogenous hormone fibroblast growth factor 23 (FGF23). Elevated FGF23 levels are seen in CKD patients. Current research has demonstrated that FGF23 directly modulates the immune response and host defense to bacterial infections. FGF23 also impairs the activation and recruitment of neutrophils, which are the main immune effector cells required for host defense against bacterial infections. In addition, while FGF23 levels reduce leukocyte recruitment and functions, inflammatory conditions may also-in a reverse fashion contribute to elevated FGF23 levels in the circulation. In this context, altered hypoxia inducible factor 1alpha signaling and iron metabolism may contribute to intact FGF23 (iFGF23) production. This review examines evidence on the role of FGF23 in inflammation, immune cell function and recruitment as well as the regulation of FGF23 during inflammation and the clinical implications of this process for the immune system in individuals with CKD. Clinical observations and laboratory investigations indicate an important role of FGF23 in directly modulating leukocyte activation and recruitment behavior with consequences on host defense against bacterial infections. This novel observation may in part explain the increased infectious risk among patients with CKD. However, studies of FGF23 neutralization also revealed increased mortality after sustained administration over several weeks in rats. Thus, therapeutic interventions targeting FGF23 must be carefully evaluated. PMID- 27659126 TI - Effect of high-protein meals during hemodialysis combined with lanthanum carbonate in hypoalbuminemic dialysis patients: findings from the FrEDI randomized controlled trial. AB - Background: Inadequate protein intake and hypoalbuminemia, indicators of protein energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels. Methods: We conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin <4.0 g/dL recruited between July 2010 and October 2011 from eight Southern California dialysis units. Patients were randomly assigned to receive high-protein (50-55 g) meals during dialysis, providing 400-500 mg phosphorus, combined with lanthanum carbonate versus low-protein (<1 g) meals during dialysis, providing <20 mg phosphorus. Prescribed nonlanthanum phosphorus binders were continued over an 8-week period. The primary composite outcome was a rise in serum albumin of >=0.2 g/dL while maintaining phosphorus between 3.5-<5.5 mg/dL. Secondary outcomes included achievement of the primary outcome's individual endpoints and changes in mineral and bone disease and inflammatory markers. Results: Among 106 participants who satisfied the trial entrance criteria, 27% ( n = 15) and 12% ( n = 6) of patients in the high-protein versus low-protein hemodialysis meal groups, respectively, achieved the primary outcome (intention-to-treat P-value = 0.045). A lower proportion of patients in the high protein versus low-protein intake groups experienced a meaningful rise in interleukin-6 levels: 9% versus 31%, respectively (P = 0.009). No serious adverse events were observed. Conclusion: In hypoalbuminemic hemodialysis patients, high protein meals during dialysis combined with lanthanum carbonate are safe and increase serum albumin while controlling phosphorus. PMID- 27659128 TI - CKD to ESRD transition: does assessment of kidney function matter? PMID- 27659129 TI - Rare subtype(s) and frequency of multi-viral subtype high-risk human papilloma virus infection in high-grade squamous intraepithelial lesion and squamous cell carcinoma in a cervical carcinoma prevalent developing country: a multiplex real time polymerase chain reaction-based pilot study. AB - BACKGROUND: Bangladesh, with a population of 160 million and nearly half being women, has the 4th highest rate of cervical carcinoma deaths in the world. It is projected that ~500,000 of these women would die of this entirely preventable cancer by 2030. HPV vaccination is not widely offered in Bangladesh. This pilot study is designed to find out the prevalence of rare and multi-viral high-risk HPV (hrHPV) subtype(s) infection which may help strategize a large scale vaccination program in tackling cervical carcinoma in the country. METHODS: Forty cases of cervical High-Grade squamous intraepithelial lesion (HSIL) and Squamous cell carcinoma (SqCa) were collected. DNA was extracted from tissue representing HSIL and SqCa and multiplex PCR was run to identify all 15 hrHPV subtypes along with known positive controls. RESULTS: Of the total, 27 cases were biopsies/cones and 13 were hysterectomies including 5 HSIL and 35 SqCa. Infection caused by rare subtypes, hrHPV 45 and 52, were found in only two cases. Multi-subtype infection, detected in 28 % cases, was limited to HPV16/18 in all cases but one; one case showed hrHPV16/52 combination. CONCLUSION: A remarkable homogeneity of hrHPV 16 infection is noted in women with HSIL & SqCa in this country in these limited samples. This finding is in sharp contrast to the reports from western countries of frequent multi-viral and rare subtype hrHPV infection. This pilot study suggests that a vaccination program may be highly effective in controlling cervical cancer there. A larger study, however, is required to ratify the findings. PMID- 27659130 TI - Systematic review of renal carcinoma prognostic factors. AB - CONTEXT AND OBJECTIVES: The natural history of renal cell carcinoma is heterogeneous. Some scenarios can be found in terms of clinical presentation, clinical evolution or type of recurrence (local/metastatic). The aim of this publication is to analyze the most important prognostic factors published in the literature. EVIDENCE ACQUISITION: A literature review ob published papers was performed using the Pubmed, from first Motzer's classification published in 1999 to 2015, according to PRISMA declaration. Search was done using the following keywords: kidney neoplasm, kidney cancer, renal cell carcinoma, prognostic factors, mortality, survival and disease progression. Papers were classified according to level of evidence, the number of patients included and the type of study performed. EVIDENCE SYNTHESIS: The evolution in the knowledge of molecular pathways related to renal oncogenesis and the new targeted therapies has left to remain obsolete the old prognostic models. It's necessary to perform a continuous review to actualize nomograms and to adapt them to the new scenarios. CONCLUSIONS: Is necessary to perform a proper external validation of existing prognostic factors using prospective and multicentric studies to add them into the daily urologist clinical practice. PMID- 27659131 TI - Heavy Metal Concentration in Periwinkle - Tympanotomus fuscatus in Iko River Estuary, Nigeria. AB - BACKGROUND: Heavy metals are intrinsic, natural constituents of our environment and are generally present in small amounts in natural aquatic environments. Humans may be contaminated by organic and inorganic pollutants associated with aquatic systems by consumption of contaminated aquatic foods from the environment. Relevant patents relating to heavy metal concentration in aquatic molluscs were reviewed. Gastropods; a promising bio-indicator and bio-monitoring subject, abound in brackish ecosystems in the Niger Delta, and are easily available for collection. Iko River Estuary, in Niger Delta zone, is one of the popular coastal areas of Nigeria where massive oil exploitation, exploration, production and refining processes take place. METHODS: The concentration of five heavy metals; Cadmium (Cd), Copper (Cu), Lead (Pb), Mercury (Hg) and Zinc (Zn) in the tissues of periwinkle; Typanotonus fuscatus, a gastropod bought from fishers fishing along the coast of Iko River Estuary was determined using UNICAM Solar Atomic Absorption Spectrophotometer 969 model for five months. RESULTS: The results showed that Cd ranged from 68.83-130.5mg/kg with a mean value of 104.47+/ 23.85mg/kg, Cu ranged from 34.9-73.62mg/kg with a mean value of 57.70+/ 17.19mg/kg, Pb ranged between 54.27-102.54mg/kg with a mean value of 85.03+/ 18.52mg/kg, Mercury ranged from 0.01-1.84mg/kg with a mean value of 0.41+/ 0.80mg/kg and Zn ranged from 270.2-508.16mg/kg with a mean of 384.99+/ 103.99mg/kg. The sequence of heavy metal concentration in the tissue of periwinkle was; Zn ? Cd ? Pb ? Cu ? Hg while the sequence of non-essential metals was Cd ? Pb ? Hg. CONCLUSION: Except for Mercury, the mean concentration of the metals was above the maximum permissible limits recommended by relevant bodies and organizations. Hence, there is need for regular monitoring of heavy metal concentrations in this water body and the aquatic organism inhabitants because of the long term effects. PMID- 27659132 TI - Local Anaesthetic Effect of Methanolic Leaves Extract of Lannea schimperi (Hoschst. Ex Rich) Eng. AB - BACKGROUND: Local anaesthetics provide relief from pain when applied locally to nerve tissue by blocking conduction of sensory nerve impulse from the receptor to the brain cortex. OBJECTIVE: This study aimed at evaluating local anaesthetic activity of the methanolic leaves extract of Lannea schimperi. METHODS: Six groups of five animals were used; groups I-IV were used for intracutaneous wheal test in guinea pigs for infiltration anaesthesia, while group V and VI were used for guinea pig corneal reflex method of surface anaesthesia. RESULTS: The result indicated a significant ( 0.05) dose dependent local anaesthetic activity of the methanolic leaves extract of Lannea schimperi with faster onset and longer duration of action at 24 mg/ml than at 12 mg/ml of the extract. Additions of 5 MUg of adrenaline into the 24 mg/ml preparation also prolonged the duration of local anaesthetic activity of the extract. The extract at 24 mg/ml significantly (0.05) inhibited corneal reflex, lidocaine was used as a standard drug in positive control group, while normal saline was used as negative control in all the treated groups. CONCLUSION: The patent data therefore revealed that the methanolic leaves extract Lannea schimperi possess local anaesthetic principles that may require further scientific elucidation. PMID- 27659133 TI - [Adapting the diet due to health reasons: Nursing intervention in patients with renal lithiasis]. AB - The urolithiasis, with a high incidence nowadays, including formations caused by gallstone of uric acid, has a high correlation to our lifestyles and dietary habits. Through a clinic case, it is intended to review the main nursing actions that may occur with this pathology. To achieve this, the data collected on physical examination and nursing assessment on the model of Virginia Henderson, while the full care plan is developed. The results show the need to establish a standardized healthy education intervention, related to a low-pruine healthy diet for people that suffer this disease. The amount of complications and problems associated with recidivism of hospital accommodation because of the ignorance of gallstone cases increase the risk of reducing the quality of life of the patients. PMID- 27659134 TI - High incidence and persistence of airborne allergen sensitization up to age 19 years. AB - BACKGROUND: Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization. METHODS: All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1516 participated in all three examinations. RESULTS: Prevalence of any positive SPT increased from 20.6% at age 7-8 years to 30.6% at 11-12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7-8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7-8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6-2.8), urban living, OR 1.9 (95% CI 1.2-2.9), and male sex, OR 1.3 (95% CI 1.0-1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7-1.0), and furry animals at home, OR 0.7 (95% CI 0.7-0.9). Incidence after age 11-12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon. CONCLUSION: The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12 years, the factors urban living, number of siblings, and male sex lost their importance. PMID- 27659135 TI - Adult pollen diet essential for egg maturation by a solitary Osmia bee. AB - Reproduction is a nutritionally costly activity for many insects, as their eggs are rich in lipids and proteins. That cost seems especially acute for non-social bees, which for their size, lay enormous eggs. All adult female bees visit flowers, most of them to collect pollen and nectar, or sometimes oils, to feed their progeny. For adult bees, the need for pollen feeding has only been detailed for the honey bee, Apis mellifera. To experimentally test for the reproductive value of adult pollen feeding by a non-social bee, Osmia californica (Hymenoptera: Apiformes: Megachilidae), young female bees plus males were released into large glasshouse cages provided with either a male-fertile sunflower cultivar or a pollen-less one. Females regularly visited and drank nectar from flowers of both cultivars. Abundant orange pollen was seen regularly in guts of females confined with the male-fertile sunflowers, indicative of active pollen ingestion. All females' terminal oocytes (next egg to be laid) were small at emergence. Oocytes of females confined with the pollen-less sunflowers remained small, despite frequent nectaring and exposure to other floral stimuli. In contrast, the basal oocytes of female O. californica with access to pollen had swelled to full size within ten days following emergence, enabling them to lay eggs in provided nest tubes. Adult females of this solitary bee required dietary pollen to reproduce; nitrogen stores acquired as larvae were inadequate. Early and regular pollen feeding in part paces the onset and maximum tempo of solitary bees' lifetime reproductive output. PMID- 27659136 TI - Reliability of SRS-22 and ODI by phone: a step toward making PROs more accessible. PMID- 27659137 TI - Inaccurate information on facet joint injections in the Medicare population. PMID- 27659138 TI - Facet injection trends in the Medicare population, response. PMID- 27659139 TI - Letter concerning "Segmental pelvic correlation (SPeC): a novel approach to understanding sagittal plane spinal alignment" by Anwar et al. PMID- 27659140 TI - Reply to letter concerning "Segmental Pelvic Correlation (SPeC): a novel approach to understanding sagittal plane spinal alignment". PMID- 27659141 TI - Adjacent segment infection complicates long segment fusion in elderly patients. PMID- 27659142 TI - Reply to "Letter to the Editor: adjacent segment infection complicates long segment fusion in elderly patients". PMID- 27659143 TI - Immune and Pancreatic beta Cell Interactions in Type 1 Diabetes. AB - The autoimmune destruction of the pancreatic islet beta cells is due to a targeted lymphocyte attack. Different T cell subsets communicate with each other and with the insulin-producing beta cells in this process, with evidence not only of damage to the tissue cells but also of lymphocyte regulation. Here we explore the various components of the immune response as well as the cellular interactions that are involved in causing or reducing immune damage to the beta cells. We consider these in the light of the possibility that understanding them may help us identify therapeutic targets to reduce the damage and destruction leading to type 1 diabetes. PMID- 27659144 TI - Perilipin 2 and Age-Related Metabolic Diseases: A New Perspective. AB - Perilipin 2 (Plin2), a protein associated with the metabolism of intracellular lipid droplets (LDs), has long been considered only for its role in lipid storage. However, the manipulation of its expression affects the severity of a variety of metabolic and age-related diseases, such as fatty liver, insulin resistance and type 2 diabetes (T2D), cardiovascular disease, atherosclerosis, sarcopenia, and cancer, suggesting that this protein may play a role in these pathological conditions. In particular, its downregulation in mice prevents or mitigates some of the above mentioned diseases. Conversely, in humans high levels of Plin2 are present in sarcopenia, hepatic steatosis, atherosclerosis, and some types of cancer. We propose that inhibition of Plin2 might be a strategy to counteract several metabolic and age-related diseases. PMID- 27659145 TI - Prognosis of small bowel adenocarcinoma in Crohn's disease compares favourably with de novo small bowel adenocarcinoma. AB - AIM: Limited data exist on Crohn's disease (CD)-associated small bowel adenocarcinoma (SBA). A large-scale retrospective cohort study was conducted comparing the clinical features and outcome of CD-associated SBA and de novo SBA. METHOD: Data for patients with small bowel adenocarcinoma were gathered from the 1992-2010 United States Surveillance, Epidemiology and End Results cancer registry-Medicare linked database. We identified 2123 patients, of whom 179 had CD-associated and 1944 de novo SBA. The main outcome measures were overall survival (OS) and cancer-specific survival (CSS). RESULTS: CD-associated SBA was most commonly located in the ileum (62% vs 31%, P < 0.0001). CD patients were diagnosed at an earlier stage (I/II), compared with de novo SBA (55% vs 32%, P < 0.0001), and were more likely to undergo surgery (81% vs 72%, P = 0.0016). Chemotherapy use was similar (25% vs 21%, P = 0.1886). Patients with CD associated SBA had better 5-year OS (43% vs 34%, P = 0.0121) but a similar CSS (65% vs 64%, P = 0.77). There was no difference in the OS between the cohorts when stratified by stage. On multivariate analysis, CD was not significantly related to OS [hazard ratio (HR) 0.97, 95% CI: 0.79-1.20, P = 0.7889]. Surgery and the extent of lymphadenectomy improved OS for all SBA patients (HR 0.73, 95% CI: 0.60-0.88, P = 0.001), whereas chemotherapy did not (HR 1.13, 95% CI: 0.99 1.28, P = 0.0665). CONCLUSION: Patients with CD-associated SBA present at an earlier stage than patients with de novo SBA, they receive more surgery but similar rates of chemotherapy, and have similar OS and CSS. The presence of CD does not worsen survival after treatment of SBA. PMID- 27659146 TI - Liquid-Crystalline Ionic Liquids as Ordered Reaction Media for the Diels-Alder Reaction. AB - Liquid-crystalline ionic liquids (LCILs) are ordered materials that have untapped potential to be used as reaction media for synthetic chemistry. This paper investigates the potential for the ordered structures of LCILs to influence the stereochemical outcome of the Diels-Alder reaction between cyclopentadiene and methyl acrylate. The ratio of endo- to exo-product from this reaction was monitored for a range of ionic liquids (ILs) and LCILs. Comparison of the endo:exo ratios in these reactions as a function of cation, anion and liquid crystallinity of the reaction media, allowed for the effects of liquid crystallinity to be distinguished from anion effects or cation alkyl chain length effects. These data strongly suggest that the proportion of exo-product increases as the reaction media is changed from an isotropic IL to a LCIL. A detailed molecular dynamics (MD) study suggests that this effect is related to different hydrogen bonding interactions between the reaction media and the exo- and endo transition states in solvents with layered, smectic ordering compared to those that are isotropic. PMID- 27659147 TI - Dendritic transport element of human arc mRNA confers RNA degradation activity in a translation-dependent manner. AB - Localization of mRNA in neuronal cells is a critical process for spatiotemporal regulation of gene expression. Cytoplasmic localization of mRNA is often conferred by transport elements in 3' untranslated region (UTR). Activity regulated cytoskeleton-associated protein (arc) mRNA is one of the localizing mRNAs in neuronal cells, and its localization is mediated by dendritic targeting element (DTE). As arc mRNA has introns in its 3' UTR, it was thought that arc mRNA is a natural target of nonsense-mediated mRNA decay (NMD). Here, we show that DTE in human arc 3' UTR has destabilizing activity of RNA independent of NMD pathway. DTE alone was able to cause instability of the reporter mRNA and this degradation was dependent on translation. Our results indicate that DTE has dual activity in mRNA transport and degradation, which suggests the novel spatiotemporal regulation mechanism of activity-dependent degradation of the mRNA. PMID- 27659148 TI - CorMatrix valved conduit in a porcine model: long-term remodelling and biomechanical characterization. AB - OBJECTIVES: Porcine small intestinal submucosa extracellular matrix (CorMatrix; CorMatrix Cardiovascular, Rosewell, GA) is a relatively novel tissue substitute used in cardiovascular applications. We investigated the biological reaction and remodelling of CorMatrix as a tri-leaflet valved conduit in a pig model. We hypothesized that CorMatrix maintains a durable architecture as a valved conduit and remodels to resemble surrounding tissues. METHODS: We fashioned the valved conduit using a 7 * 10 cm 4-ply CorMatrix sheet and placed it in the thoracic aorta of seven landrace pigs for 3, 4, 5 and 6 months. Biodegradation, replacement by native tissue, strength and durability were examined by histology, immunohistochemistry and mechanical testing. RESULTS: Four pigs, one per time frame, completed the study. The conduit lost its original architecture as a tri leaflet valve due to cusp immobility, subsequent attachment to the wall segment and consequent maintenance of a thick arterial wall-like structure. Scaffold resorption was incomplete, with disorganized inconsistent spatial and temporal degradation even at 6 months. Fibrosis, scarring and calcification started at 4 months and chronic inflammation persisted. The partially remodelled scaffold did not resemble the aortic wall, suggesting impaired remodelling. Mechanical testing showed progressive weakening of the tissues over time, which were liable to breakage. CONCLUSIONS: CorMatrix is biodegradable; however, it failed to remodel in a structured and anatomical fashion in an arterial environment. Progressive mechanical and remodelling failure in this scenario might be explained by the complexity of the conduit design and the host's chronic inflammatory response, leading to early fibrosis and calcification. PMID- 27659149 TI - A novel procedure for reconstructing an extensive hypoplastic aortic arch in older children. AB - Aortic arch reconstruction is the key to successfully repairing an interrupted aortic arch (IAA) with tubular hypoplasia of the aortic arch (THAA), especially in older children. We report a novel reconstruction technique involving aortapulmonary fusion that was used to treat THAA in a 9 year-old patient with IAA. In this procedure, the underside of the aortic arch and the upside of the main pulmonary artery were fused to reconstruct the aortic arch. The short-term outcome of the procedure has been promising. This procedure may represent an alternative for repairing extensive THAA in older children. PMID- 27659150 TI - Meta-analysis of open surgical repair versus hybrid arch repair for aortic arch aneurysm. AB - OBJECTIVE: To conduct a meta-analysis of available comparative studies evaluating hybrid arch repair versus open surgical repair of aortic arch aneurysm. METHODS: A literature search was performed using PubMed, Embase and Web of Science to identify any studies comparing the results of hybrid arch repair with open surgical repair of aortic arch aneurysm. Study quality was assessed with the Newcastle-Ottawa Scale. Statistical heterogeneity was estimated using the chi square test. A random-effects model was used to illustrate heterogeneity. Publication bias was evaluated by funnel plots. RESULTS: Seven retrospective cohort studies from 2009 to 2016 comprising 727 patients were included. Among these patients, 269 were treated with hybrid arch repair and 458 with open surgical repair. There was no significant difference in operative mortality (OR 0.75; 95% CI 0.41-1.39; P = 0.37), permanent neurological deficit (OR 1.24; 95% CI 0.73-2.13; P = 0.42), late mortality (2 years) (OR 3.41; 95% CI 0.83-14.03; P = 0.09) or renal failure (OR 0.80; 95% CI 0.40-1.61; P = 0.53). Interestingly, the meta-analysis indicated that the hybrid group needed more reinterventions (OR 3.43; 95% CI 1.72-6.84; P = 0.0005). CONCLUSIONS: We found no strong evidence indicating that hybrid arch repair is superior to open surgical repair. Furthermore, the hybrid arch repair resulted in more reinterventions despite the fact that it was a less invasive procedure; it also required fewer days in the hospital. Further studies with large numbers of participants and long-term follow ups are necessary to confirm the effectiveness of hybrid arch repair. PMID- 27659151 TI - Trends in isolated coronary artery bypass grafting over the last decade. AB - OBJECTIVES: The purpose of this study was to assess the impact on hospital mortality and morbidity of extensive myocardial revascularization, using arterial grafts in patients undergoing isolated coronary artery bypass grafting (CABG). METHODS: Our prospective perioperative database was used to define two groups of patients who underwent isolated CABG with cardiopulmonary bypass, based on the years in which the operation was performed: Group A (2000-2003; 898 patients) and Group B (2009-2012; 1249 patients). The baseline and operative characteristics and outcomes were compared. RESULTS: Several significant changes in perioperative variables were observed. Group B included higher percentages of patients aged over 80 years (+58.1%), with diabetes (+32.0%) and with a history of percutaneous coronary intervention (+24.9%). The mean EuroSCORE II was significantly increased from 2.5 +/- 4.4% in Group A to 3.2 +/- 5.7% in Group B (P= 0.001). The mean number of distal anastomoses was significantly increased over time (total: 2.6 +/ 0.8 vs 3.1 +/- 1.0, P< 0.0001 and with arterial grafts: 1.6 +/- 0.8 vs 2.6 +/- 0.9, P< 0.0001). In-hospital mortality was low and did not significantly differ between Groups A and B (1.3 vs 2.4%; P= 0.08). Significant increases of new-onset atrial fibrillation (11.7 vs 21.9%, P= 0.017) and deep sternal infection (0.2 vs 1.1%, P= 0.017) were observed in Group B, compared with Group A. In multivariate analysis, extensive use of arterial grafts was not a risk factor of hospital mortality or sternal morbidity. CONCLUSIONS: Despite the increasing risk profiles of patients undergoing CABG, extensive myocardial revascularization using arterial grafts is associated with good early results. PMID- 27659152 TI - Superficial femoral artery access for transcatheter aortic valve replacement. AB - Different vascular accesses have been described for the delivery of a transcatheter aortic bioprosthesis. We report the use of the superficial femoral artery (SFA) as the arterial site of puncture with surgical cut-down. It may be a reasonable access alternative to the other classical routes, especially in the setting of either obese patients with elevated body mass index or in the presence of high femoral artery bifurcation. This route seems to be feasible with a low profile risk. PMID- 27659153 TI - Characterization of serum matrix metalloproteinase 2/9 levels in patients with ascending aortic aneurysms. AB - OBJECTIVES: The objectives of this study were to identify interrelations between matrix metalloproteinase-2 (MMP2)/MMP9 levels and clinical variables in patients with aortic root/ascending aortic aneurysms and to describe comorbidities as possible biasing factors in the widely discussed correlation of serum MMP levels and aortic diameter. METHODS: Serum MMP9 and MMP2 levels were quantified in 32 consecutive patients with ascending aortic and/or aortic root aneurysms (>45 mm) at the Heart Center University of Freiburg from May 2013 to January 2014. The influence of comorbidities and medication on serum MMP2 and MMP9 levels was studied. We took into account ascending aortic diameter (aAD), aortic valve configuration, hypertension, age and hyperlipidaemia as factors possibly altering serum MMP levels. The relation between serum MMP levels and aAD was examined by a correlation test based on ranks. RESULTS: Serum MMP2 levels and aAD correlated positively. Correlation was increased in patients without hyperlipidaemia (Spearman's rho = 0.62, P = 0.008 in patients without hyperlipidaemia; rho = 0.409, P = 0.020 in all patients). Serum MMP9 levels did not correlate with aAD and showed greater variation. Serum MMP9 levels were significantly associated with hyperlipidaemia (P = 0.037). CONCLUSIONS: The distinct correlation patterns in patients with and without hyperlipidaemia have to be considered when defining the potential of MMP2 as a biomarker in future studies. The relation between MMP9 and hyperlipidaemia has to be further investigated. PMID- 27659154 TI - Thoraco-abdominal aortic aneurysm rupture secondary to lymphocytic lymphoma. AB - We present the case of a 60-year old woman with a ruptured thoraco-abdominal aortic aneurysm (TAAA). It was a Type IV TAAA in the Crawford Classification. A mycotic origin was suspected as she had a known history of lymphocytic lymphoma. She underwent thoraco-abdominal aortic replacement with a good surgical result. Histopathological examination revealed destruction of the aortic layers due to inflammatory lymphomatous aortic infiltration. The patient fully recovered. PMID- 27659155 TI - Puncturing Plaques. AB - PURPOSE: To test and validate magnetic resonance imaging (MRI) sequences for peripheral artery lesion characterization and relate the MRI characteristics to the amount of force required for a guidewire to puncture peripheral chronic total occlusions (CTOs) as a surrogate for immediate failure of endovascular therapy. METHODS: Diseased superficial femoral, popliteal, and tibial artery segments containing 55 atherosclerotic lesions were excised from the amputated limbs of 7 patients with critical limb ischemia. The lesions were imaged at high resolution (75 MUm3 voxels) with T2-weighted (T2W) and ultrashort echo time (UTE) sequences on a 7-T MR scanner. The MR images (n=15) were validated with micro-computed tomography and histology. CTOs (n=40) were classified by their MR signal characteristics as "soft" (signals indicating fat, thrombus, microchannels, or loose fibrous tissue), "hard" (collagen and/or speckled calcium signals), or "calcified" (calcified nodule signals). A 2-kg load cell advanced the back end of a 0.035-inch stiff guidewire at a fixed displacement rate (0.05 mm/s) through the CTOs, and the forces required to cross each lesion were measured. RESULTS: T2W images showed fat as hyperintense and hardened tissue as hypointense. Calcium and thrombus appeared as a signal void in conventional MRI sequences but were easily identified in UTE images (thrombus was hyperintense and calcium hypointense). MRI accurately differentiated "hard," "soft," and "calcified" CTOs based on associated guidewire puncture force. The guidewire could not enter "calcified" CTOs (n=6) at all. "Hard" CTOs (n=9) required a significantly higher (p<0.001) puncture force of 1.71+/-0.51 N vs 0.43+/-0.36 N for "soft" CTOs (n=25). CONCLUSION: MRI characteristics of PAD lesions correlate with guidewire puncture forces, an important aspect of crossability. Future work will determine if clinical MR scanners can be used to predict success in peripheral vascular interventions. PMID- 27659156 TI - Ambulatory bilateral neck exploration for primary hyperparathyroidism: is it safe? AB - BACKGROUND: We sought to determine if bilateral neck exploration (BNE) for hyperparathyroidism could be performed safely in an ambulatory setting (same-day discharge) when compared with focused parathyroidectomy. METHODS: A retrospective review of 503 patients who underwent parathyroidectomy from 2010 to 2015 was performed. Focused parathyroidectomy was compared with BNE. Only patients with positive localization and no prior operations were included. RESULTS: Forty-nine percent of patients underwent focused parathyroidectomy and 51% had BNE. BNE patients were more likely to have 1 or more glands removed (35% vs 14%, P < .01) and longer operative times (median 50 vs 41 minutes, P < .01). There were no differences in the rate of same-day discharge, transient hypocalcemia, emergency department visits, and readmissions. CONCLUSIONS: In this study, BNE for hyperparathyroidism was associated with excision of more parathyroid glands and slightly longer operative times. However, BNE had equal rates of same-day discharges and safety profile. PMID- 27659158 TI - Prophylactic mesh placement for prevention of incisional hernia after open bariatric surgery: a systematic review and meta-analysis. AB - BACKGROUND: Prophylactic mesh during laparotomy has been shown to be effective in preventing postoperative incisional hernia (IH) in high-risk patients. Since obesity is a risk factor for IH, we wished to determine whether mesh prevents IH in open and laparoscopic bariatric surgery patients. METHODS: We conducted a systematic review of the literature with meta-analysis. Seven studies met inclusion criteria. We abstracted data regarding postoperative IH development, surgical site infection, and seroma or wound leakage and performed meta-analysis. RESULTS: The prophylactic mesh group had significantly decreased odds of developing IH than the standard closure group (odds ratio, .30, 95% CI, .13 to .68, P = .004). No included studies evaluated outcomes after prophylactic mesh during laparoscopic bariatric surgery. CONCLUSIONS: Prophylactic mesh during open bariatric surgery appears to be beneficial in reducing postoperative IH without significant increasing the odds of surgical site infection or seroma or wound leakage. Higher quality studies, including those in laparoscopic patients, and cost-utility analysis, are needed to support routine use of this intervention. PMID- 27659157 TI - Surgical immune interventions for solid malignancies. AB - BACKGROUND: The purpose of this study was to systematically review clinically translatable immunotherapeutic agents that are delivered regionally for solid malignancies. DATA SOURCES: PubMed and ClinicalTrials.gov were searched for published and registered clinical trials, respectively. The search yielded 334 relevant publications, of which 116 articles were included for review after exclusion criteria were applied. CONCLUSIONS: There has been an increase in the regional administration of cell-based and viral vector-based clinical trials over the last 5 years. Surgical interventions have been developed for intrapleural, intracranial, intraperitoneal, and intratumoral routes of access to enhance the local delivery of these therapies. Multimodality therapies that combine regional immunotherapy with other local and systemic therapies are demonstrating continued growth as the field of immunotherapy continues to expand. PMID- 27659159 TI - Optimizing Clinical Drug Product Performance: Applying Biopharmaceutics Risk Assessment Roadmap (BioRAM) and the BioRAM Scoring Grid. AB - The aim of Biopharmaceutics Risk Assessment Roadmap (BioRAM) and the BioRAM Scoring Grid is to facilitate optimization of clinical performance of drug products. BioRAM strategy relies on therapy-driven drug delivery and follows an integrated systems approach for formulating and addressing critical questions and decision-making (J Pharm Sci. 2014,103(11): 3777-97). In BioRAM, risk is defined as not achieving the intended in vivo drug product performance, and success is assessed by time to decision-making and action. Emphasis on time to decision making and time to action highlights the value of well-formulated critical questions and well-designed and conducted integrated studies. This commentary describes and illustrates application of the BioRAM Scoring Grid, a companion to the BioRAM strategy, which guides implementation of such an integrated strategy encompassing 12 critical areas and 6 assessment stages. Application of the BioRAM Scoring Grid is illustrated using published literature. Organizational considerations for implementing BioRAM strategy, including the interactions, function, and skillsets of the BioRAM group members, are also reviewed. As a creative and innovative systems approach, we believe that BioRAM is going to have a broad-reaching impact, influencing drug development and leading to unique collaborations influencing how we learn, and leverage and share knowledge. PMID- 27659160 TI - Solid-Phase and Oscillating Solution Crystallization Behavior of (+)- and (-)-N Methylephedrine. AB - This work involves the study of the solid-phase and solution crystallization behavior of the N-methylephedrine enantiomers. A systematic investigation of the melt phase diagram of the enantiomeric N-methylephedrine system was performed considering polymorphism. Two monotropically related modifications of the enantiomer were found. Solubilities and the ternary solubility phase diagrams of N-methylephedrine enantiomers in 2 solvents [isopropanol:water, 1:3 (Vol) and (2R, 3R)-diethyl tartrate] were determined in the temperature ranges between 15 degrees C and 25 degrees C, and 25 degrees C and 40 degrees C, respectively. Preferential nucleation and crystallization experiments at higher supersaturation leading to an unusual oscillatory crystallization behavior as well as a successful preferential crystallization experiment at lower supersaturation are presented and discussed. PMID- 27659161 TI - In vivo multiphoton imaging of immune cell dynamics. AB - Multiphoton imaging has been utilized to analyze in vivo immune cell dynamics over the last 15 years. Particularly, it has deepened the understanding of how immune responses are organized by immune cell migration and interactions. In this review, we first describe the following technical advances in recent imaging studies that contributed to the new findings on the regulation of immune responses and inflammation. Improved multicolor imaging of immune cell behavior has revealed that their interactions are spatiotemporally coordinated to achieve efficient and long-term immunity. The use of photoactivatable and photoconvertible fluorescent proteins has increased duration and volume of cell tracking, even enabling the analysis of inter-organ migration of immune cells. In addition, visualization of immune cell activation using biosensors for intracellular calcium concentration and signaling molecule activities has started to give further mechanistic insights. Then, we also introduce recent imaging analyses of interactions between immune cells and non-immune cells including endothelial, fibroblastic, epithelial, and nerve cells. It is argued that future imaging studies that apply updated technical advances to analyze interactions between immune cells and non-immune cells will be important for thorough physiological understanding of the immune system. PMID- 27659163 TI - Balloon dilation of sinus ostia in the Department of Defense: Diagnoses, actual indications, and outcomes. AB - OBJECTIVES/HYPOTHESIS: To determine the primary diagnoses for which balloon catheter dilation (BCD) of sinus ostia is being employed in a profit-blind health care system, the Department of Defense. STUDY DESIGN: Retrospective chart review. METHODS: From January 1, 2011 to December 31, 2013, 319 consecutive patient charts were reviewed for International Classification of Diseases, Ninth Edition (ICD-9) diagnoses, presence of chronic rhinosinusitis (CRS) defined by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), preoperative Lund-Mackay scores, nasal endoscopy findings, sinuses dilated, postoperative outcomes, and complications. RESULTS: Of the 319 patients identified, 217 had sufficient documentation to be included. A CRS ICD-9 code was applied in 182 of 217 (83.9%) and recurrent acute rhinosinusitis in 12 of 217 (5.6%). Only 50.5% of CRS patient charts met criteria using EPOS guidelines. In contrast, 39.6% met the ICD-9 criteria for atypical facial pain. Patients with Lund-Mackay scores <= 4 were reviewed for number of sinuses dilated. Eighty-eight of 123 patients (71.5%) had sinuses dilated that were free from opacification/mucosal edema on preoperative imaging. CONCLUSIONS: Balloon dilation of sinus ostia has an expanding role in treating sinus disease. In the studied population, BCD is often utilized for alternate indications for which there is currently no evidence of efficacy. Future studies are needed to evaluate the efficacy of this technology in treating these alternate indications. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:544-549, 2017. PMID- 27659162 TI - Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression. AB - T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Enhanced T-type channel expression has been causally linked to a number of pathological conditions including peripheral painful diabetic neuropathy. Recently, it was demonstrated that asparagine-linked glycosylation not only plays an essential role in regulating cell surface expression of Cav3.2 channels, but may also support glucose-dependent potentiation of T-type currents. However, the underlying mechanisms by which N-glycosylation and glucose levels modulate the expression of T-type channels remain elusive. In the present study, we show that site-specific N-glycosylation of Cav3.2 is essential to stabilize expression of the channel at the plasma membrane. In contrast, elevated external glucose concentration appears to potentiate intracellular forward trafficking of the channel to the cell surface, resulting in an increased steady-state expression of the channel protein at the plasma membrane. Collectively, our study indicates that glucose and N-glycosylation act in concert to control the expression of Cav3.2 channels, and that alteration of these mechanisms may contribute to the altered expression of T-type channels in pathological conditions. PMID- 27659164 TI - Improved specific loss power on cancer cells by hyperthermia and MRI contrast of hydrophilic Fex Co1-x Fe2 O4 nanoensembles. AB - Ferrite-based ferri/superparamagnetic nanoparticles can be rapidly heated by an external alternating magnetic field (AMF) to induce tissue necrosis of the adjacent microenvironment, but in addition provide magnetic resonance imaging (MRI) contrast utilizing enhanced water relaxivity. Here we characterized nanoensembles of Fe-Co mixed spinel ferrites (i.e. Fex Co1-x Fe2 O4 , where x ranges from 0.2 to 0.8) synthesized by chemical co-precipitation. With nanoensembles of increasing Co content the saturation magnetization improved, while lattice parameter remained relatively constant. MRI water (transverse) relaxivity at 11.7 T was also boosted with increasing Co content. Efficiency of AMF-induced heating was quite comparable for the nanoensembles with either chitosan or polyethylene glycol (PEG) coating except for PEG-coated Fe0.2 Co0.8 Fe2 O4 , which was twice as less efficient as others. While toxicity of the nanoensembles with either coating examined on 9L tumor cell cultures showed no significant differences, upon AMF exposure (i.e. heat-induced necrosis) Fex Co1-x Fe2 O4 composition with different values of x showed quite dramatic effects on cell death of tumor cells with both coatings. This study lays the ground work for further characterization of other mixed spinel ferrites, and in addition we expect that chitosan and PEG coated Fex Co1-x Fe2 O4 of all the compositions will have good potential for preclinical applications in vivo. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27659165 TI - Remineralizing potential of a 60-s in vitro application of Tooth Mousse Plus. AB - BACKGROUND: No published studies exist on the remineralizing potential of Tooth Mousse Plus(r) (TMP) when applied for less than 3 min. AIM: To evaluate (i) the remineralizing potential of TMP on artificial carious lesions, when applied thrice daily for 60 s, and (ii) the benefit of using a fluoridated dentifrice prior to TMP application. DESIGN: Carious lesions, 120-200 MUm deep, were produced by placing molars in demineralizing solution for 96 h, and sections 100 150 MUm thick were then randomly assigned to four groups. Specimens were treated thrice daily with a non-fluoridated (Group A), or 1000 ppm F dentifrice (Group B), or TMP (Group C), or a 1000 ppm F dentifrice followed by TMP application (Group D), and then subjected to a 10-day pH cycling model. Lesion evaluation involved polarizing light microscopy and microradiography. RESULTS: Post treatment maximum mineral content at the surface zone (Vmax ) was significantly increased and lesion depth (LD) significantly decreased in Group C, while only the Vmax increased in Group D. Increase in LD was observed in Group B; however, no significant differences were noted in percentage LD changes between groups B, C, and D (P > 0.05). CONCLUSIONS: TMP applied for 60 s significantly remineralized the artificial carious lesions. No additional benefit was evident when TMP was preceded by treatment with 1000 ppm F dentifrice. PMID- 27659166 TI - Protective effects of resveratrol and its analogs on age-related macular degeneration in vitro. AB - Damage of retinal pigment epithelial (RPE) cells by A2E may be critical for age related macular degeneration (AMD) management. Accumulation and photooxidation of A2E are known to be one of the critical causes in AMD. Here, we evaluated the protective effect of resveratrol (RES), piceatannol (PIC) and RES glycones on blue-light-induced RPE cell death caused by A2E photooxidation. A2E treatment followed by blue light exposure caused significant damages on human RPE cells (ARPE-19). But the damages were attenuated by post- and pre-treatment of RES and PIC in our in vitro models. The results of cell free system and FAB-MS analysis clearly showed that the reduction of A2E by blue light exposure was significantly rescued, and that oxidized forms of A2E were significantly reduced by RES or PIC treatment. Besides, RES or PIC inhibited the intracellular accumulation of A2E. Not only RES and PIC but RES glycones showed protection of ARPE-19 cells against A2E and blue-light-induced photo-damage. These findings demonstrate that RES and its analogs may have protective effects against A2E and blue-light-induced ARPE 19 cell death through regulation of A2E accumulation as well as photooxidation of A2E. Thus RES and its analogs may be beneficial for AMD treatment. PMID- 27659167 TI - Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells. AB - The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3 sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority. PMID- 27659168 TI - Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies. AB - In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as marginal structural Cox model in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995-2008). PMID- 27659169 TI - Feasibility of reusing time-matched controls in an overlapping cohort. AB - The methods developed for secondary analysis of nested case-control data have been illustrated only in simplified settings in a common cohort and have not found their way into biostatistical practice. This paper demonstrates the feasibility of reusing prior nested case-control data in a realistic setting where a new outcome is available in an overlapping cohort where no new controls were gathered and where all data have been anonymised. Using basic information about the background cohort and sampling criteria, the new cases and prior data are "aligned" to identify the common underlying study base. With this study base, a Kaplan-Meier table of the prior outcome extracts the risk sets required to calculate the weights to assign to the controls to remove the sampling bias. A weighted Cox regression, implemented in standard statistical software, provides unbiased hazard ratios. Using the method to compare cases of contralateral breast cancer to available controls from a prior study of metastases, we identified a multifocal tumor as a risk factor that has not been reported previously. We examine the sensitivity of the method to an imperfect weighting scheme and discuss its merits and pitfalls to provide guidance for its use in medical research studies. PMID- 27659170 TI - Minimally invasive surgery for lumbar spinal stenosis. PMID- 27659171 TI - Influence of sagittal plane malpositioning of the patella on anterior knee pain after tibia intramedullary nailing. AB - PURPOSE: Anterior knee pain (AKP) is one of the most common complications after tibia intramedullary surgery. We evaluated changes in patellar tendon length after tibia intramedullary nailing surgery using a transtendinous approach and assessed the importance of nail position in relation to the anterior tibial cortex and joint line. METHODS: Two surgeons blinded to patients' pain status measured both the knee Insall-Salvati and Caton-Deschamps indexes on 30 degrees flexion lateral knee X-rays of 33 patients. Superior nail prominence (the distance from the proximal tip of the nail to the tibial plateau) and anterior nail prominence (the distance from the anterior tip of the nail to the anterior tibial cortex) were measured on the CT. RESULTS: Clinical assessment showed that 10 patients (30 %) had AKP at the last follow-up. HSS and Lysholm scores and the incidence of AKP were similar between patients whose IM nails were removed and those who still had them. HSS score, Insall-Salvati, and Caton-Deschamps indexes were significantly lower in the operated extremity than in the healthy limb at last follow-up. No association was demonstrated between AKP and nail position in relation to the anterior tibial cortex or tibial plateau. CONCLUSIONS: According to our study, although the patellar tendon shortened significantly on the affected side compared with the contralateral side, these measurements did not correlate with the presence or absence of pain. AKP and functional knee scores after tibia IM nailing using a transtendinous approach were not associated with nail position in relation to the anterior tibial cortex or tibial plateau. LEVEL OF EVIDENCE: Level 3 (Case control study). PMID- 27659173 TI - Length separation of single-walled carbon nanotubes and its impact on structural and electrical properties of wafer-level fabricated carbon nanotube-field-effect transistors. AB - For an industrial realization of devices based on single-walled carbon nanotube (SWCNTs) such as field-effect transistors (FETs) it becomes increasingly important to consider technological aspects such as intrinsic device structure, integration process controllability as well as yield. From the perspective of a wafer-level integration technology, the influence of SWCNT length on the performance of short-channel CNT-FETs is demonstrated by means of a statistical and comparative study. Therefore, a methodological development of a length separation process based on size-exclusion chromatography was conducted in order to extract well-separated SWCNT dispersions with narrowed length distribution. It could be shown that short SWCNTs adversely affect integrability and reproducibility, underlined by a 25% decline of the integration yield with respect to long SWCNTs. Furthermore, it turns out that the significant changes in electrical performance are directly linked to a SWCNT chain formation in the transistor channel. In particular, CNT-FETs with long SWCNTs outperform reference and short SWCNTs with respect to hole mobility and subthreshold controllability by up to 300% and up to 140%, respectively. As a whole, this study provides a statistical and comparative analysis towards chain-less CNT-FETs fabricated with a wafer-level technology. PMID- 27659172 TI - The peri-esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging. AB - An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named 'aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection 'aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named 'peri-esophageal compartment' and the posterior compartment 'para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long-standing paradigm that no such structure exists. A comprehensive, detailed description of the peri esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI. PMID- 27659174 TI - 'Photosystem II: the water splitting enzyme of photosynthesis and the origin of oxygen in our atmosphere'. AB - About 3 billion years ago an enzyme emerged which would dramatically change the chemical composition of our planet and set in motion an unprecedented explosion in biological activity. This enzyme used solar energy to power the thermodynamically and chemically demanding reaction of water splitting. In so doing it provided biology with an unlimited supply of reducing equivalents needed to convert carbon dioxide into the organic molecules of life while at the same time produced oxygen to transform our planetary atmosphere from an anaerobic to an aerobic state. The enzyme which facilitates this reaction and therefore underpins virtually all life on our planet is known as Photosystem II (PSII). It is a pigment-binding, multisubunit protein complex embedded in the lipid environment of the thylakoid membranes of plants, algae and cyanobacteria. Today we have detailed understanding of the structure and functioning of this key and unique enzyme. The journey to this level of knowledge can be traced back to the discovery of oxygen itself in the 18th-century. Since then there has been a sequence of mile stone discoveries which makes a fascinating story, stretching over 200 years. But it is the last few years that have provided the level of detail necessary to reveal the chemistry of water oxidation and O-O bond formation. In particular, the crystal structure of the isolated PSII enzyme has been reported with ever increasing improvement in resolution. Thus the organisational and structural details of its many subunits and cofactors are now well understood. The water splitting site was revealed as a cluster of four Mn ions and a Ca ion surrounded by amino-acid side chains, of which seven provide direct ligands to the metals. The metal cluster is organised as a cubane structure composed of three Mn ions and a Ca2+ linked by oxo-bonds with the fourth Mn ion attached to the cubane. This structure has now been synthesised in a non-protein environment suggesting that it is a totally inorganic precursor for the evolution of the photosynthetic oxygen-evolving complex. In summary, the overall structure of the catalytic site has given a framework on which to build a mechanistic scheme for photosynthetic dioxygen generation and at the same time provide a blue-print and incentive to develop catalysts for artificial photo electrochemical systems to split water and generate renewable solar fuels. PMID- 27659176 TI - Psychology, Medicine and Collaborative Innovation: An Appreciative Reply to Kirch and Ast. PMID- 27659177 TI - Can a Tarlov cyst radiculopathy simulate meralgia paresthetica? PMID- 27659175 TI - Eating disorder severity and functional impairment: moderating effects of illness duration in a clinical sample. AB - PURPOSE: The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. METHODS: The study included 159 patients diagnosed with bulimia nervosa, binge eating disorder or eating disorder not otherwise specified. Regression analysis was applied to assess the effect of the hypothesized moderators and mediators. Eating disorder severity was measured with the Eating Disorder Examination Questionnaire, functional impairment was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. RESULTS: Duration of illness significantly moderated the relationship between eating disorder severity and functional impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress and functional impairment; the strongest relationship was seen for patients with a shorter duration of illness. Body mass index was not a significant moderator of the relationship between ED severity and functional impairment. CONCLUSIONS: Overall, this study established a link between ED severity, psychological distress and functional impairment indicating that both eating disorder severity and psychological distress are more strongly related to impaired role functioning for patients with more recent onset of an eating disorder. More research in the complex relationship between ED severity and functional impairment is needed. PMID- 27659179 TI - Determination of Porto-Azygos Shunt Anatomy in Dogs by Computed Tomography Angiography. AB - OBJECTIVE: To describe the morphology of porto-azygos shunts in a large series of dogs using computed tomography (CT) angiography. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=36) with porto-azygos shunts. METHODS: CT angiography was performed in dogs subsequently proven to have a porto-azygos shunt. The origin and insertion of the shunts were assessed on native images. The diameter of the porto-azygos shunt and the portal vein, cranial and caudal to the shunt origin, were measured. The porto-azygos shunt anatomy was studied on three-dimensional images. RESULTS: All porto-azygos shunts originated either in the left gastric vein (33 left gastro-azygos shunts) or the right gastric vein (3 right gastro azygos shunts). Two left gastro-azygos shunts had concurrent caval-azygos continuation and 2 right gastro-azygos shunts had a caudal splenic loop. All shunts crossed the diaphragm through the esophageal hiatus. The majority of porto azygos shunts (32) followed a straight pathway after traversing the diaphragm, although 4 shunts followed a tortuous route. All shunts terminated in the thoracic part of the azygos vein, perpendicular to the aorta. The shunt diameter at insertion was only 3 mm on average. The insertion site was consistently the narrowest part of the shunt. CONCLUSION: CT angiography was well suited to provide anatomic details of porto-azygos shunts and comprehensively documented that all porto-azygos shunts had a thoracic terminus, after crossing the diaphragm through the esophageal hiatus. Different shunt types existed with minor variations. PMID- 27659180 TI - ABSTRACTS OF OSTEOPOROSIS CONFERENCE 2016. PMID- 27659178 TI - Twenty-Four-Hour Ambulatory Pulse Wave Analysis in Hypertension Management: Current Evidence and Perspectives. AB - The predictive value of vascular biomarkers such as pulse wave velocity (PWV), central arterial pressure (CAP), and augmentation index (AIx), obtained through pulse wave analysis (PWA) in resting conditions, has been documented in a variety of patient groups and populations. This allowed to make appropriate recommendations in clinical practice guidelines of several scientific societies. Due to advances in technologies, largely operator-independent methods are currently available for estimating vascular biomarkers also in ambulatory conditions, over the 24 h. According to the acceptable accuracy and reproducibility of 24-h ambulatory PWA, it appears to be a promising tool for evaluating vascular biomarkers in daily life conditions. This approach may provide an opportunity to further improve the early cardiovascular screening in subjects at risk. However, concerning the clinical use of PWA over the 24 h in ambulatory conditions at the moment, there is no sufficient evidence to support its routine clinical use. In particular, long-term outcome studies are needed to show the predictive value of 24-h PWV, CAP, and AIx values, provided by these devices, over and beyond peripheral blood pressure, and to answer the many technical and clinical questions still open. To this regard, the VASOTENS Registry, an international observational prospective study recently started, will help providing answers on a large sample of hypertensive patients recruited worldwide. PMID- 27659181 TI - The triterpenoid CDDO-imidazolide reduces immune cell infiltration and cytokine secretion in the KrasG12D;Pdx1-Cre (KC) mouse model of pancreatic cancer. AB - Because the 5-year survival rate for pancreatic cancer remains under 10%, new drugs are needed for the prevention and treatment of this devastating disease. Patients with chronic pancreatitis have a 12-fold higher risk of developing pancreatic cancer. LSL-KrasG12D/+;Pdx-1-Cre (KC) mice replicate the genetics, symptoms and histopathology found in human pancreatic cancer. Immune cells infiltrate into the pancreas of these mice and produce inflammatory cytokines that promote tumor growth. KC mice are particularly sensitive to the effects of lipopolysaccharide (LPS), as only 48% of KC mice survived an LPS challenge while 100% of wildtype (WT) mice survived. LPS also increased the percentage of CD45+ immune cells in the pancreas and immunosuppressive Gr1+ myeloid-derived suppressor cell in the spleen of these mice. The triterpenoid CDDO-imidazolide (CDDO-Im) not only reduced the lethal effects of LPS (71% survival) but also decreased the infiltration of CD45+ cells into the pancreas and the percentage of Gr1+ myeloid-derived suppressor cell in the spleen of KC mice 4-8 weeks after the initial LPS challenge. While the levels of inflammatory cytokine levels were markedly higher in KC mice versus WT mice challenged with LPS, CDDO-Im significantly decreased the production of IL-6, CCL-2, vascular endothelial growth factor and G-CSF in the KC mice. All of these cytokines are prognostic markers in pancreatic cancer or play important roles in the progression of this disease. Disrupting the inflammatory process with drugs such as CDDO-Im might be useful for preventing pancreatic cancer, especially in high-risk populations. PMID- 27659183 TI - Performance and safety of collagenated xenogeneic bone block for lateral alveolar ridge augmentation and staged implant placement. A monocenter, prospective single arm clinical study. AB - OBJECTIVES: To assess the clinical safety and performance of collagenated xenogeneic bone block (CXBB) for lateral alveolar ridge augmentation and two stage implant placement. MATERIAL & METHODS: In ten patients exhibiting a single tooth gap, the surgical procedure included the preparation of mucoperiosteal flaps, a rigid fixation of CXBB (Geistlich Bio-Graft(r) ) using an osteosynthesis screw, and contour augmentation. After 24 weeks of submerged healing, the primary endpoint was defined as the final ridge width sufficient to place an adequately dimensioned titanium implant at the respective sites. Secondary outcomes included, for example, the gain in ridge width (mm). Clinical parameters (e.g., bleeding on probing - BOP, probing depth - PD, mucosal recession - MR) were assessed immediately after the cementation of the crown and at the final visit. RESULTS: At 24 weeks, implant placement could be achieved in 8 of 10 patients exhibiting a mean gain in ridge width (mean +/- SD) of 3.88 +/- 1.75 mm. Histological analysis has pointed to a homogeneous osseous organization of CXBB. The changes of mean BOP, PD, and MR values at the final visit amounted to 16.62 +/- 32.02%, 0.04 +/- 0.21 mm, and -0.04 +/- 0.12 mm, respectively. CONCLUSIONS: CXBB may be successfully used to support lateral alveolar ridge augmentation and two-stage implant placement. PMID- 27659182 TI - Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients. AB - PURPOSE: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. METHODS: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy. RESULTS: We describe a very plausible mechanism for methotrexate neurotoxicity in pediatric leukemia patients involving reduction in methionine and consequential disruption of myelin production. We provide evidence that a number of commonly prescribed drugs in pediatric leukemia management interact with the same folate biosynthetic pathways and/or reduce functional vitamin B12 levels and hence are likely to increase the toxicity of methotrexate in these patients. We also present a brief case study supporting out hypothesis that nitrous oxide contributes to methotrexate neurotoxicity and a nutritional study, showing that vitamin B12 deficiency is common in pediatric leukemia patients. CONCLUSIONS: Use of nitrous oxide in pediatric leukemia patients at the same time as methotrexate use should be avoided especially as many suitable alternative anesthetic agents exist. Clinicians should consider monitoring levels of vitamin B12 in patients suspected of having methotrexate induced neurotoxic effects. PMID- 27659184 TI - Direct synthesis of nanodiamonds by femtosecond laser irradiation of ethanol. AB - Carbon nanomaterials exhibit novel characteristics including enhanced thermal, electrical, mechanical, and biological properties. Nanodiamonds; first discovered in meteorites are found to be biocompatible, non-toxic and have distinct optical properties. Here we show that nanodiamonds with the size of <5 nm are formed directly from ethanol via 1025 nm femtosecond laser irradiation. The absorption of laser energy by ethanol increased non-linearly above 100 MUJ accompanied by a white light continuum arises from fs laser filamentation. At laser energy higher than 300 MUJ, emission spectra of C, O and H in the plasma were detected, indicating the dissociation of C2H5OH. Nucleation of the carbon species in the confined plasma within the laser filaments leads to the formation of nanodiamonds. The energy dependence and the roles of the nonlinear phenomenon to the formation of homogeneous nanodiamonds are discussed. This work brings new possibility for bottom-up nanomaterials synthesis based on nano and ultrafast laser physics. PMID- 27659186 TI - [Not Available]. PMID- 27659185 TI - Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals. AB - The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food-evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U-shape association between BMI and monetary-evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food-evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary-evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666-677, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27659187 TI - A case report of simultaneous orthotopic liver transplantation and jejunectomy. AB - BACKGROUND: Liver transplantation (LT) accompanied by jejunectomy to treat patients with acute or chronic hepatic cirrhosis with thrombosis in the portal system is extremely rare. CASE PRESENTATION: A 47-year-old man presented with hematemesis and melena, and a diagnosis of decompensated cirrhosis, chronic portal vein thrombosis (PVT) and secondary gastro-esophageal variceal hemorrhage was made. Coagulants were administered, but portal vein thrombi occurred rapidly, and gastrointestinal bleeding recurred shortly thereafter. The patient underwent LT, phlebothrombectomy and a partial jejunectomy. His recovery from a fistula was uneventful, and follow-up visits over 70 months were unremarkable. CONCLUSION: Liver transplantation and partial jejunectomy is a feasible and effective surgical option for select patients with end-stage liver disease accompanied by acute portal venous thrombosis. PMID- 27659188 TI - Disparate acidification and calcium carbonate desaturation of deep and shallow waters of the Arctic Ocean. AB - The Arctic Ocean is acidifying from absorption of man-made CO2. Current predictive models of that acidification focus on surface waters, and their results argue that deep waters will acidify by downward penetration from the surface. Here we show, with an alternative model, the rapid, near simultaneous, acidification of both surface and deep waters, a prediction supported by current, but limited, saturation data. Whereas Arctic surface water responds directly by atmospheric CO2 uptake, deeper waters will be influenced strongly by intrusion of mid-depth, pre-acidified, Atlantic Ocean water. With unabated CO2 emissions, surface waters will become undersaturated with respect to aragonite by 2105 AD and could remain so for ~600 years. In deep waters, the aragonite saturation horizon will rise, reaching the base of the surface mixed layer by 2140 AD and likely remaining there for over a millennium. The survival of aragonite-secreting organisms is consequently threatened on long timescales. PMID- 27659189 TI - Measuring Brain Tissue Integrity during 4 Years Using Diffusion Tensor Imaging. AB - BACKGROUND AND PURPOSE: DTI is an MR imaging measure of brain tissue integrity. Little is known regarding the long-term longitudinal evolution of lesional and nonlesional tissue DTI parameters in multiple sclerosis and the present study examines DTI evolution over 4 years. MATERIALS AND METHODS: Twenty-one patients with multiple sclerosis were imaged for up to 48 months after starting natalizumab therapy. Gadolinium-enhancing lesions at baseline, chronic T2 lesions, and normal-appearing white matter were followed longitudinally. T2 lesions were subclassified as black holes and non-black holes. Within each ROI, the average values of DTI metrics were derived by using Analysis of Functional Neuro Images software. The longitudinal trend in DTI metrics was estimated by using a mixed-model regression analysis. RESULTS: A significant increase was observed for axial diffusivity (P < .001) in gadolinium-enhancing lesions and chronic T2 lesions during 4 years. No significant change in radial diffusivity either in normal-appearing white matter or lesional tissue was observed. The evolution of axial diffusivity was different in gadolinium-enhancing lesions (P < .001) and chronic T2 lesions (P = .02) compared with normal-appearing white matter. CONCLUSIONS: An increase in axial diffusion in both gadolinium-enhancing lesions and T2 lesions may relate to the complex evolution of chronically demyelinated brain tissue. Pathologic changes in normal-appearing white matter are likely more subtle than in lesional tissue and may explain the stability of these measures with DTI. PMID- 27659190 TI - Influence of Small Vessel Disease and Microstructural Integrity on Neurocognitive Functioning in Older Individuals: The DANTE Study Leiden. AB - BACKGROUND AND PURPOSE: Small vessel disease is a major cause of neurocognitive dysfunction in the elderly. Small vessel disease may manifest as white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy, all of which are visible on conventional MR imaging or as microstructural changes determined by diffusion tensor imaging. This study investigated whether microstructural integrity is associated with neurocognitive dysfunction in older individuals, irrespective of the conventional features of small vessel disease. MATERIALS AND METHODS: The study included 195 participants (75 years of age or older) who underwent conventional 3T MR imaging with DTI to assess fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Cognitive tests were administered to assess cognitive domains, and the Geriatric Depression Scale-15 and Apathy Scale of Starkstein were used to assess symptoms of depression and apathy, respectively. The association between DTI measures and neurocognitive function was analyzed by using linear regression models. RESULTS: In gray matter, a lower fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity were associated with worse executive function, psychomotor speed, and overall cognition and, in white matter, also with memory. Findings were independent of white matter hyperintensities, lacunar infarcts, and cerebral microbleeds. However, after additional adjustment for normalized brain volume, only lower fractional anisotropy in white and gray matter and higher gray matter radial diffusivity remained associated with executive functioning. DTI measures were not associated with scores on the Geriatric Depression Scale-15 or the Apathy Scale of Starkstein. CONCLUSIONS: Microstructural integrity was associated with cognitive but not psychological dysfunction. Associations were independent of the conventional features of small vessel disease but attenuated after adjusting for brain volume. PMID- 27659191 TI - Prospective Validation of Two 4D-CT-Based Scoring Systems for Prediction of Multigland Disease in Primary Hyperparathyroidism. AB - BACKGROUND AND PURPOSE: Patients with multigland primary hyperparathyroidism are at higher risk for missed lesions on imaging and failed parathyroidectomy. The purpose of this study was to prospectively validate the ability of previously derived predictive score systems, the composite multigland disease score, and the multiphase multidetector contrast-enhanced CT (4D-CT) composite multigland disease score, to identify patients with a high likelihood of multigland disease. MATERIALS AND METHODS: This was a prospective study of 71 patients with primary hyperparathyroidism who underwent 4D-CT and successful parathyroidectomy. The size and number of lesions identified on 4D-CT, serum calcium levels, and parathyroid hormone levels were collected. A composite multigland disease score was calculated from 4D-CT imaging findings and the Wisconsin Index (the product of the serum calcium and parathyroid hormone levels). A 4D-CT multigland disease score was obtained by using the CT data alone. RESULTS: Twenty-eight patients with multigland disease were compared with 43 patients with single-gland disease. Patients with multigland disease had a significantly smaller lesion size (P < .01) and a higher likelihood of having either >=2 or 0 lesions identified on 4D CT (P < .01). Composite multigland disease scores of >=4, >=5, and 6 had specificities of 72%, 86%, and 100% for multigland disease, respectively. 4D-CT multigland disease scores of >=3 and 4 had specificities of 74% and 88%. CONCLUSIONS: Predictive scoring systems based on 4D-CT data, with or without laboratory data, were able to identify a subgroup of patients with a high likelihood of multigland disease in a prospectively accrued population of patients with primary hyperparathyroidism. These scoring systems can aid in surgical planning. PMID- 27659192 TI - Comparison of High-Resolution MR Imaging and Digital Subtraction Angiography for the Characterization and Diagnosis of Intracranial Artery Disease. AB - BACKGROUND AND PURPOSE: High-resolution MR imaging has recently been introduced as a promising diagnostic modality in intracranial artery disease. Our aim was to compare high-resolution MR imaging with digital subtraction angiography for the characterization and diagnosis of various intracranial artery diseases. MATERIALS AND METHODS: Thirty-seven patients who had undergone both high-resolution MR imaging and DSA for intracranial artery disease were enrolled in our study (August 2011 to April 2014). The time interval between the high-resolution MR imaging and DSA was within 1 month. The degree of stenosis and the minimal luminal diameter were independently measured by 2 observers in both DSA and high resolution MR imaging, and the results were compared. Two observers independently diagnosed intracranial artery diseases on DSA and high-resolution MR imaging. The time interval between the diagnoses on DSA and high-resolution MR imaging was 2 weeks. Interobserver diagnostic agreement for each technique and intermodality diagnostic agreement for each observer were acquired. RESULTS: High-resolution MR imaging showed moderate-to-excellent agreement (interclass correlation coefficient = 0.892-0.949; kappa = 0.548-0.614) and significant correlations (R = 0.766-892) with DSA on the degree of stenosis and minimal luminal diameter. The interobserver diagnostic agreement was good for DSA (kappa = 0.643) and excellent for high-resolution MR imaging (kappa = 0.818). The intermodality diagnostic agreement was good (kappa = 0.704) for observer 1 and moderate (kappa = 0.579) for observer 2, respectively. CONCLUSIONS: High-resolution MR imaging may be an imaging method comparable with DSA for the characterization and diagnosis of various intracranial artery diseases. PMID- 27659193 TI - Yield of Repeat 3D Angiography in Patients with Aneurysmal-Type Subarachnoid Hemorrhage. AB - BACKGROUND AND PURPOSE: Aneurysmal-type subarachnoid hemorrhage is a serious disease with high morbidity and mortality. When no aneurysm is found, the patient remains at risk for rebleeding. Negative findings for SAH on angiography range from 2% to 24%. Most previous studies were based on conventional 2D imaging. 3D rotational angiography depicts more aneurysms than 2D angiography. The purpose of this study was to evaluate the yield of repeat 3D rotational angiography in patients with aneurysmal-type SAH with negative initial 3D rotational angiography findings and to classify the initial occult aneurysms. MATERIALS AND METHODS: Between March 2013 and January 2016, 292 patients with SAH and an aneurysmal bleeding pattern were admitted. Of these 292 patients, 30 (10.3%; 95% CI, 7.3% 14.3%) had initial negative 3D rotational angiography findings within 24 hours. These patients underwent a second 3D rotational angiography after 7-10 days. RESULTS: In 8 of 30 patients (26.7%; 95% CI, 14.0%-44.7%) with initial negative 3D rotational angiography findings, a ruptured aneurysm was found on repeat 3D rotational angiography. Three of 8 initial occult aneurysms were very small (1-2 mm), 2 were supraclinoid carotid artery dissecting aneurysms (2 and 8 mm), 2 were small (1 and 3 mm) basilar perforator aneurysms, and 1 was a 3-mm vertebral artery dissecting aneurysm. CONCLUSIONS: In 10% of patients with aneurysmal-type SAH, initial 3D rotational angiography findings were negative, and in 1 in 4, repeat 3D rotational angiography demonstrated a ruptured aneurysm. Initial occult aneurysms were dissecting aneurysms of perforators or main arteries or were very small (1-2 mm) or both. Our results indicate that repeat 3D rotational angiography is mandatory in patients with initial 3D rotational angiography findings negative for aneurysmal-type SAH. PMID- 27659194 TI - PQRS and the MACRA: Value-Based Payments Have Moved from Concept to Reality. PMID- 27659195 TI - Gynaecomastia. PMID- 27659196 TI - Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers. AB - Soils are facing new environmental stressors, such as titanium dioxide nanoparticles (TiO2-NPs). While these emerging pollutants are increasingly released into most ecosystems, including agricultural fields, their potential impacts on soil and its function remain to be investigated. Here we report the response of the microbial community of an agricultural soil exposed over 90 days to TiO2-NPs (1 and 500 mg kg-1 dry soil). To assess their impact on soil function, we focused on the nitrogen cycle and measured nitrification and denitrification enzymatic activities and by quantifying specific representative genes (amoA for ammonia-oxidizers, nirK and nirS for denitrifiers). Additionally, diversity shifts were examined in bacteria, archaea, and the ammonia-oxidizing clades of each domain. With strong negative impacts on nitrification enzyme activities and the abundances of ammonia-oxidizing microorganism, TiO2-NPs triggered cascading negative effects on denitrification enzyme activity and a deep modification of the bacterial community structure after just 90 days of exposure to even the lowest, realistic concentration of NPs. These results appeal further research to assess how these emerging pollutants modify the soil health and broader ecosystem function. PMID- 27659197 TI - CIBZ Regulates Mesodermal and Cardiac Differentiation of by Suppressing T and Mesp1 Expression in Mouse Embryonic Stem Cells. AB - The molecular mechanisms underlying mesodermal and cardiac specification from embryonic stem cells (ESCs) are not fully understood. Here, we showed that the BTB domain-containing zinc finger protein CIBZ is expressed in mouse ESCs but is dramatically downregulated during ESC differentiation. CIBZ deletion in ESCs induced specification toward mesoderm phenotypes and their differentiation into cardiomyocytes, whereas overexpression of CIBZ delayed these processes. During ESC differentiation, CIBZ loss-and-gain-of-function data indicate that CIBZ negatively regulates the expressions of Brachyury (T) and Mesp1, the key transcriptional factors responsible for the specification of mammalian mesoderm and cardiac progenitors, respectively. Chromatin immunoprecipitation assays showed that CIBZ binds to T and Mesp1 promoters in undifferentiated ESCs, and luciferase assays indicate that CIBZ suppresses T and Mesp1 promoters. These findings demonstrate that CIBZ is a novel regulator of mesodermal and cardiac differentiation of ESCs, and suggest that CIBZ-mediated cardiac differentiation depends on the regulation of these two genes. PMID- 27659198 TI - Human leukocyte antigen class 1 genotype distribution and analysis in persons with active tuberculosis and household contacts from Central Uganda. AB - BACKGROUND: To determine the distribution of Human leukocyte antigen (HLA) class I genotypes in a Ugandan population of persons with tuberculosis (TB) and establish the relationship between class I HLA types and Mycobacterium tuberculosis (MTB) disease. METHODS: Blood samples were drawn from HIV negative individuals with active TB and HIV negative household controls. DNA was extracted from blood samples and HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. RESULTS: HLA-A*02, B*15, C*07, C*03, B*58, C*04, A*01, A*74, C*02 and A*30 were the dominant genotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the household controls with only HLA-A*03 allele showing a statistically significant difference (p = 0.017 crude; OR = 6.29 and p = 0.016; OR = 11.67 after adjustment for age). However, after applying the Benjamini and Hochberg adjustment for multiple comparisons the difference was no longer statistically significant (p = 0.374 and p = 0.176 respectively). CONCLUSIONS: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results do not show a positive association between the HLA class I alleles and TB in this Ugandan population however the study sample was too small to draw any firm conclusions about the role of HLA class I alleles and TB development in Uganda. PMID- 27659199 TI - Violent obsessions are associated with suicidality in an OCD analog sample of college students. AB - The picture of suicide in obsessive-compulsive disorder (OCD) is unclear because previous research did not uniformly control for depressive symptoms when examining the relationship between OCD and suicidality. Specific links between OC symptom dimensions and suicidality were also not adequately studied. As such, we investigated specific associations between OC symptom dimensions and suicidality, beyond the contribution of depressive symptoms, in an OCD analog sample of college students, a group traditionally at risk for suicide. One hundred and forty-six college students (103 females; 43 males) who exceeded the clinical cut off for OC symptoms on the Obsessive-Compulsive Inventory, Revised (OCI-R) were recruited. Participants completed an online questionnaire containing measures that assessed suicidality and OC and depressive symptom severity. Total OC symptom severity, unacceptable thoughts, and especially violent obsessions exhibited significant positive zero-order correlations with suicidality. However, analyses of part correlations indicated that only violent obsessions had a significant unique association with suicidality after controlling for depressive symptoms. Our findings support the hypothesis that violent obsessions have a specific role in suicidality beyond the influence of depressive symptoms in an OCD analog sample of college students. A strong clinical focus on suicide risk assessment and safety planning in college students reporting violent obsessions is therefore warranted. Future related research should employ longitudinal or prospective designs and control for other possible comorbid symptoms in larger and more representative samples of participants formally diagnosed with OCD in order to verify the generalizability of our findings to these groups. PMID- 27659200 TI - Goat K222-PrPC polymorphic variant does not provide resistance to atypical scrapie in transgenic mice. AB - Host prion (PrPC) genotype is a major determinant for the susceptibility to prion diseases. The Q/K222-PrPC polymorphic variant provides goats and mice with high resistance against classical scrapie and bovine spongiform encephalopathy (BSE); yet its effect against atypical scrapie is unknown. Here, transgenic mice expressing the goat wild-type (wt) or the K222-PrPC variant were intracerebrally inoculated with several natural cases of atypical scrapie from sheep and goat and their susceptibility to the prion disease was determined. Goat wt and K222-PrPC transgenic mice were 100% susceptible to all the atypical scrapie isolates, showing similar survival times and almost identical disease phenotypes. The capacity of the K222-PrPC variant to replicate specifically the atypical scrapie strain as efficiently as the goat wt PrPC, but not the classical scrapie or cattle-BSE as previously reported, further suggests the involvement of concrete areas of the host PrPC in the strain-dependent replication of prions. PMID- 27659201 TI - Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms. AB - Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR-/-) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression, and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA. PMID- 27659202 TI - Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice. AB - Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2WT/WT) and PKD2 catalytic activity deficient mice (PKD2SSAA/SSAA) with dextran sulfate sodium. PKD2SSAA-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2WT/WT mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2SSAA-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2SSAA-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function. PMID- 27659203 TI - Single-pulse enhanced coherent diffraction imaging of bacteria with an X-ray free electron laser. AB - High-resolution imaging offers one of the most promising approaches for exploring and understanding the structure and function of biomaterials and biological systems. X-ray free-electron lasers (XFELs) combined with coherent diffraction imaging can theoretically provide high-resolution spatial information regarding biological materials using a single XFEL pulse. Currently, the application of this method suffers from the low scattering cross-section of biomaterials and X ray damage to the sample. However, XFELs can provide pulses of such short duration that the data can be collected using the "diffract and destroy" approach before the effects of radiation damage on the data become significant. These experiments combine the use of enhanced coherent diffraction imaging with single shot XFEL radiation to investigate the cellular architecture of Staphylococcus aureus with and without labeling by gold (Au) nanoclusters. The resolution of the images reconstructed from these diffraction patterns were twice as high or more for gold-labeled samples, demonstrating that this enhancement method provides a promising approach for the high-resolution imaging of biomaterials and biological systems. PMID- 27659205 TI - Dibenzothiophene Sulfone-Based Phosphine Oxide Electron Transporters with Unique Asymmetry for High-Efficiency Blue Thermally Activated Delayed Fluorescence Diodes. AB - Three asymmetrical electron transporters as dibenzothiophene sulfone (DBSO) diphenylphosphine oxide (DPPO) hybrids, collectively named mnDBSODPO, were designed and prepared. All of these materials achieve the high triplet energy of ~3.0 eV to restrain the exciton linkage from emissive layers. The dependence of inductive and steric effects for DPPO groups on the substitution position, the intermolecular interaction suppression, the encapsulations of high-polar DBSO cores, and the favorable electrical performance are successfully integrated on 36DBSODPO, which can simultaneously suppress the exciton quenching by formation of an interfacial dipole and enhancing the charge flux balance. As a result, 36DBSODPO endowed its tetralayer blue thermally activated delayed fluorescence (TADF) devices with impressive performance, including the maximum external quantum efficiency around 19%, and reduced efficiency roll-offs, which verifies the great potential of asymmetrical electron transporting materials for highly efficient TADF devices. PMID- 27659204 TI - Risk factors for community-acquired pneumonia in children under five years of age in the post-pneumococcal conjugate vaccine era in Brazil: a case control study. AB - BACKGROUND: Pneumonia plays an important role in children's morbidity and mortality. In Brazil, epidemiological and social changes occurred concomitantly with the universal introduction of the 10-valent pneumococcal conjugate vaccine. This study identified risk factors for pneumonia following the implementation of a pneumococcal vaccination program. METHODS: A hospital-based, case-control study involving incident cases of pneumonia in children aged 1-59 months was conducted between October 2010 and September 2013 at a tertiary hospital in northeastern Brazil. The diagnosis of pneumonia was based on the World Health Organization (WHO) criteria. The control group consisted of children admitted to the day hospital ward for elective surgery. Children with comorbidities were excluded. The risk factors for pneumonia that were investigated were among those classified by the WHO as definite, likely and possible. A multivariate analysis was performed including variables that were significant at p <= 0.25 in the bivariate analysis. RESULTS: The study evaluated 407 children in the case group and 407 children in the control group. Household crowding (OR = 2.15; 95 % CI, 1,46-3,18) and not having been vaccinated against the influenza virus (OR = 3.59; 95 % CI, 2,62-4.91) were the only factors found to increase the likelihood of pneumonia. Male gender constituted a protective factor (OR = 0.53; 95 % CI, 0,39-0,72). CONCLUSION: Changes on risk factors for pneumonia were most likely associated with the expansion of the vaccination program and social improvements; however, these improvements were insufficient to overcome inequalities, given that household crowding remained a significant risk factor. The protection provided by the influenza vaccine must be evaluated new etiological studies. Furthermore, additional risk factors should be investigated. PMID- 27659206 TI - Patients with severe-to-profound hearing impairment and simultaneous severe vision impairment: a quality-of-life study. AB - CONCLUSIONS: Patients with severe vision impairment in combination with severe-to profound hearing loss seem to have a higher risk for effects on QoL, including: mobility, the ability to provide self-care and perform usual activities, and levels of anxiety and depression, compared with patients with only severe-to profound hearing loss. OBJECTIVES: To study the quality-of-life (QoL) and audiological rehabilitation of the severely vision-impaired patient population among adults with severe-to-profound hearing loss in Sweden. METHOD: A study of data collected from 543 patients with severe-to-profound hearing loss combined with severe vision impairment among the total of 2319 persons registered in the Swedish Quality Register of Otorhinolaryngology. QoL was measured with the following instruments: EQ5D, PIRS, and HADS. Audiological rehabilitation was described and evaluated. RESULTS: The patients with dual sensory loss were younger, were more likely to live alone, and had a lower level of education than the control group. The QoL of the study group was significantly negatively affected. In total, 89% of the study group had been rehabilitated with hearing aids, while 8% had received rehabilitation with cochlear implants. A total of 32% of the study group had received extended audiological rehabilitation. PMID- 27659208 TI - Ten polymorphic microsatellite markers characterized for Schizothorax pseudaksaiensis and applied for population genetic analysis. PMID- 27659209 TI - Development, characterization and transferability of 10 novel microsatellite markers in Cotoneaster orbicularis Schltdl. (Rosaceae). PMID- 27659207 TI - Neurogenin 3 is regulated by neurotrophic tyrosine kinase receptor type 2 (TRKB) signaling in the adult human exocrine pancreas. AB - BACKGROUND: Reports of exocrine-to-endocrine reprogramming through expression or stabilization of the transcription factor neurogenin 3 (NGN3) have generated renewed interest in harnessing pancreatic plasticity for therapeutic applications. NGN3 is expressed by a population of endocrine progenitor cells that give rise exclusively to hormone-secreting cells within pancreatic islets and is necessary and sufficient for endocrine differentiation during development. In the adult human pancreas, NGN3 is expressed by dedifferentiating exocrine cells with a phenotype resembling endocrine progenitor cells and the capacity for endocrine differentiation in vitro. Neurotrophic tyrosine kinase receptor type 2 (TRKB), which regulates neuronal cell survival, differentiation and plasticity, was identified as highly overexpressed in the NGN3 positive cell transcriptome compared to NGN3 negative exocrine cells. This study was designed to determine if NGN3 is regulated by TRKB signaling in the adult human exocrine pancreas. METHODS: Transcriptome analysis, quantitative reverse transcriptase polymerase chain reaction (RTPCR) and immunochemistry were used to identify TRKB isoform expression in primary cultures of human islet-depleted exocrine tissue and human cadaveric pancreas biopsies. The effects of pharmacological modulation of TRKB signaling on the expression of NGN3 were assessed by Student's t-test and ANOVA. RESULTS: Approximately 30 % of cultured exocrine cells and 95 % of NGN3+ cells express TRKB on their cell surface. Transcriptome-based exon splicing analyses, isoform-specific quantitative RTPCR and immunochemical staining demonstrate that TRKB-T1, which lacks a tyrosine kinase domain, is the predominant isoform expressed in cultured exocrine tissue and is expressed in histologically normal cadaveric pancreas biopsies. Pharmacological inhibition of TRKB significantly decreased the percentage of NGN3+ cells, while a TRKB agonist significantly increased this percentage. Inhibition of protein kinase B (AKT) blocked the effect of the TRKB agonist, while inhibition of tyrosine kinase had no effect. Modulation of TRKB and AKT signaling did not significantly affect the level of NGN3 mRNA. CONCLUSIONS: In the adult human exocrine pancreas, TRKB-T1 positively regulates NGN3 independent of effects on NGN3 transcription. Targeting mechanisms controlling the NGN3+ cell population size and endocrine cell fate commitment represent a potential new approach to understand pancreas pathobiology and means whereby cell populations could be expanded for therapeutic purposes. PMID- 27659210 TI - Antigenic Peptide Recognition on the Human ABC Transporter TAP Resolved by DNP Enhanced Solid-State NMR Spectroscopy. AB - The human transporter associated with antigen processing (TAP) is a 150 kDa heterodimeric ABC transport complex that selects peptides for export into the endoplasmic reticulum and subsequent loading onto major histocompatibility complex class I molecules to trigger adaptive immune responses against virally or malignantly transformed cells. To date, no atomic-resolution information on peptide-TAP interactions has been obtained, hampering a mechanistic understanding of the early steps of substrate translocation catalyzed by TAP. Here, we developed a mild method to concentrate an unstable membrane protein complex and combined this effort with dynamic nuclear polarization enhanced magic angle spinning solid-state NMR to study this challenging membrane protein-substrate complex. We were able to determine the atomic-resolution backbone conformation of an antigenic peptide bound to human TAP. Our NMR data also provide unparalleled insights into the nature of the interactions between the side chains of the antigen peptide and TAP. By combining NMR data and molecular modeling, the location of the peptide binding cavity has been identified, revealing a complex scenario of peptide-TAP recognition. Our findings reveal a structural and chemical basis of substrate selection rules, which define the crucial function of this ABC transporter in human immunity and health. This work is the first NMR study of a eukaryotic transporter protein and presents the power of solid-state NMR in this growing field. PMID- 27659212 TI - Should we recommend universal aspirin for all pregnant women? AB - Low-dose aspirin has been demonstrated to reduce the incidence of preeclampsia and fetal growth restriction in at-risk populations. Its role in low-risk populations is as yet unknown. Novel preeclampsia screening tests are emerging that can predict the risk of the development of preeclampsia from as early as 11 weeks of gestation. It may be more efficacious, acceptable, and cost-effective to prescribe low-dose aspirin to all pregnant women from the first trimester as opposed to performing a screening test in the first instance. There is variation in opinion: the American College of Obstetricians and Gynecologists suggests the use of aspirin only in women who are at risk of preeclampsia, based on patient history; the National Institute for Health and Clinical Excellence, UK, and the US Preventative Services Task Force recommend the use of low-dose aspirin if there is 1 major or 2 moderate risk factors. This point-counterpoint discussion shall address (1) controversies regarding the real impact of low-dose aspirin; (2) controversies in the actual guidelines among the different national societies; (3) controversies regarding emerging preeclampsia screening tests in terms of cost-effectiveness and efficacy, and (4) points in favor of the provision of universal vs screened-positive women. PMID- 27659213 TI - Good eggs and bad eggs. PMID- 27659214 TI - Genetic diversity and phylogeography of highly zoonotic Echinococcus granulosus genotype G1 in the Americas (Argentina, Brazil, Chile and Mexico) based on 8279bp of mtDNA. AB - Echinococcus granulosus is a taeniid cestode and the etiological agent of an infectious zoonotic disease known as cystic echinococcosis (CE) or hydatid disease. CE is a serious public health concern in many parts of the world, including the Americas, where it is highly endemic in many regions. Echinococcus granulosus displays high intraspecific genetic variability and is divided into multiple genotypes (G1-G8, G10) with differences in their biology and etiology. Of these, genotype G1 is responsible for the majority of human and livestock infections and has the broadest host spectrum. However, despite the high significance to the public and livestock health, the data on genetic variability and regional genetic differences of genotype G1 in America are scarce. The aim of this study was to evaluate the genetic variability and phylogeography of G1 in several countries in America by sequencing a large portion of the mitochondrial genome. We analysed 8279bp of mtDNA for 52 E. granulosus G1 samples from sheep, cattle and pigs collected in Argentina, Brazil, Chile and Mexico, covering majority of countries in the Americas where G1 has been reported. The phylogenetic network revealed 29 haplotypes and a high haplotype diversity (Hd=0.903). The absence of phylogeographic segregation between different regions in America suggests the importance of animal transportation in shaping the genetic structure of E. granulosus G1. In addition, our study revealed many highly divergent haplotypes, indicating a long and complex evolutionary history of E. granulosus G1 in the Americas. PMID- 27659219 TI - Mental health academics in rural and remote Australia. AB - CONTEXT: The significant impact of mental ill health in rural and remote Australia has been well documented. Included among innovative approaches undertaken to address this issue has been the Mental Health Academic (MHA) project, established in 2007. Funded by the Australian Government (Department of Health), this project was established as a component of the University Departments of Rural Health (UDRH) program. All 11 UDRHs appointed an MHA. Although widely geographically dispersed, the MHAs have collaborated in various ways. The MHA project encompasses a range of activities addressing four key performance indicators. These activities, undertaken in rural and remote Australia, aimed to increase access to mental health services, promote awareness of mental health issues, support students undertaking mental health training and improve health professionals' capacity to recognise and address mental health issues. MHAs were strategically placed within the UDRHs across the country, ensuring an established academic base for the MHAs' work was available immediately. Close association with each local rural community was recognised as important. For most MHAs this was facilitated by having an established clinical role in their local community and actively engaging with the community in which they worked. In common with other rural health initiatives, some difficulties were experienced in the recruitment of suitable MHAs, especially in more remote locations. The genesis of this article was a national meeting of the MHAs in 2014, to identify and map the different types of activities MHAs had undertaken in their regions. These activities were analysed and categorised by the MHAs. These categories have been used as a guiding framework for this article. ISSUES: The challenge to increase community access to mental health services was addressed by (i) initiatives to address specific access barriers, (ii) supporting recruitment and retention of rural mental health staff, (iii) developing the skills of the existing workforce and (iv) developing innovative approaches to student placements. Strategies to promote awareness of mental health issues included workshops in rural and remote communities, specific suicide prevention initiatives and targeted initiatives to support the mental health needs of Indigenous Australians. The need for collaboration between the widely dispersed MHAs was identified as important to bridge the rural divide, to promote project cohesiveness and ensure new ideas in an emerging setting are readily shared and to provide professional support for one another as mental health academics are often isolated from academic colleagues with similar mental health interests. LESSONS LEARNED: The MHA project suggests that an integrated approach can be taken to address the common difficulties of community awareness raising of mental health issues, increasing access to mental health services, workforce recruitment and retention (access), and skill development of existing health professionals (access and awareness). To address the specific needs and circumstances of their community, MHAs have customised their activities. As in other rural initiatives, one size was found not to fit all. The triad of flexibility, diversity and connectedness (both to local community and other MHAs) describes the response identified as appropriate by the MHAs. The breadth of the MHA role to provide university sponsored educational activities outside traditional student teaching meant that the broader health workforce benefited from access to mental health training that would not otherwise have occurred. Provision of these additional educational opportunities addressed not only the need for increased education regarding mental health but also reduced the barriers commonly faced by rural health professionals in accessing quality professional development. PMID- 27659218 TI - Comparative efficacy of bilastine, desloratadine and rupatadine in the suppression of wheal and flare response induced by intradermal histamine in healthy volunteers. AB - OBJECTIVE: To compare the peripheral antihistaminic activity of bilastine, rupatadine and desloratadine in inhibiting the histamine-induced wheal and flare (W&F) response. RESEARCH DESIGN AND METHODS: Twenty-four healthy volunteers aged 18-40 years participated in this crossover, randomized, double-blind, placebo controlled clinical study. Subjects received single doses of bilastine 20 mg, desloratadine 5 mg, rupatadine 10 mg and placebo. W&F responses induced by intradermal injection of histamine 5 MUg were evaluated before treatment (basal value) and at 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after treatment. Fifteen minutes after histamine injection, W&F surface areas (cm2) were quantified using the Visitrak System. Itching sensation was evaluated using a 100 mm visual analog scale. EudraCT number: 2015-000790-13. MAIN OUTCOME MEASURES: The primary outcome measure was the percentage reduction in W&F areas after each active treatment compared with corresponding basal values. RESULTS: Bilastine induced the greatest inhibition in wheal area and was significantly superior to desloratadine and rupatadine from 1 to 12 hours (both p < .001). Rupatadine and desloratadine were better than placebo without differences between them. Maximum wheal inhibition occurred at 6 hours (bilastine 83%, desloratadine 38%, rupatadine 37%). Onset of action was 1 hour for bilastine and 4 hours for desloratadine and rupatadine. Bilastine was significantly superior to desloratadine and rupatadine for flare inhibition from 1-24 hours (both p < .001) with an onset of action at 30 minutes. Bilastine was significantly better than desloratadine (2-12 hours; at least p < .05) and rupatadine (2-9 hours; at least p < .01) for reducing itching sensation. Neither desloratadine nor rupatadine significantly reduced itching compared to placebo. All active treatments were well tolerated. CONCLUSIONS: Bilastine 20 mg induced significantly greater inhibition of the W&F response compared with desloratadine 5 mg and rupatadine 10 mg throughout the 24 hour study period, and had the fastest onset of action. Only bilastine significantly reduced itching sensation versus placebo. PMID- 27659220 TI - Pharmacological modulation in mesial temporal lobe epilepsy: Current status and future perspectives. AB - Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE. In particular, the link between neuroinflammation, GABAAR and epilepsy has been extensively studied mainly because of the relevant therapeutic implications that the pharmacological modulation of these phenomena would have in the clinical practice. In this review, we briefly summarize the studies that could pave the road to develop new disease-modifying therapeutic strategies for pharmacoresistant MTLE patients. Both clinical observations in human MTLE and experimental findings will be discussed, highlighting the potential modulatory crosstalk between the deregulation of the inhibitory (GABAergic) transmission and the sustained activation of the innate immune response. PMID- 27659221 TI - Computational operon prediction in whole-genomes and metagenomes. AB - Microbial diversity in unique environmental settings enables abrupt responses catalysed by altering the gene regulation and formation of gene clusters called operons. Operons increases bacterial adaptability, which in turn increases their survival. This review article presents the emergence of computational operon prediction methods for whole microbial genomes and metagenomes, and discusses their strengths and limitations. Most of the whole-genome operon prediction methods struggle to generalize on unrelated genomes. The applicability of universal whole-genome operon prediction methods to metagenomic data is an interesting yet less investigated question. We have evaluated the potential of various operon prediction features for genomic and metagenomic data. Most of operon prediction methods with high accuracy have been compiled into databases. Despite of the high predictive performance, the data among many databases are not completely consistent for similar species. We performed a correlation analysis between the computationally predicted operon databases and experimentally validated data for Escherichia coli, Bacillus subtilis and Mycobacterium tuberculosis. Operon prediction for most of the less characterized microbes cannot be verified due to absence of experimentally validated operons. The generation of validated information for other microbes would test the authenticity of operon databases for other less annotated microbes as well. Advances in sequencing technologies and development of better analysis methods will help researchers to overcome the technological hurdles (such as long sequencing reads and improved contig size) and further improve operon predictions and better utilize operonic information. PMID- 27659223 TI - Eulogy for the Metabolic Clinical Investigator? PMID- 27659224 TI - The Next Step Forward Is to Take a Step Back. PMID- 27659225 TI - HDL Cholesterol Story Is Dead: Long Live HDL! PMID- 27659211 TI - The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species. AB - BACKGROUND: The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control. RESULTS: The 479 Mb medfly genome is sequenced from adult flies from lines inbred for 20 generations. A high-quality assembly is achieved having a contig N50 of 45.7 kb and scaffold N50 of 4.06 Mb. In-depth curation of more than 1800 messenger RNAs shows specific gene expansions that can be related to invasiveness and host adaptation, including gene families for chemoreception, toxin and insecticide metabolism, cuticle proteins, opsins, and aquaporins. We identify genes relevant to IPM control, including those required to improve SIT. CONCLUSIONS: The medfly genome sequence provides critical insights into the biology of one of the most serious and widespread agricultural pests. This knowledge should significantly advance the means of controlling the size and invasive potential of medfly populations. Its close relationship to Drosophila, and other insect species important to agriculture and human health, will further comparative functional and structural studies of insect genomes that should broaden our understanding of gene family evolution. PMID- 27659226 TI - Exosomes in Diabetic Cardiomyopathy: The Next-Generation Therapeutic Targets? PMID- 27659227 TI - Hydrogen Sulfide Therapy in Diabetes-Accelerated Atherosclerosis: A Whiff of Success. PMID- 27659229 TI - Erratum. Adiponectin-Induced Endothelial Nitric Oxide Synthase Activation and Nitric Oxide Production Are Mediated by APPL1 in Endothelial Cells. Diabetes 2007;56:1387-1394. PMID- 27659230 TI - Erratum. Adiponectin Prevents Diabetic Premature Senescence of Endothelial Progenitor Cells and Promotes Endothelial Repair by Suppressing the p38 MAP Kinase/p16INK4A Signaling Pathway. Diabetes 2010;59:2949-2959. PMID- 27659228 TI - Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness. AB - Type 2 diabetes and cardiovascular disease are complex disorders involving metabolic and inflammatory mechanisms. Here we investigated whether sCD93, a group XIV c-type lectin of the endosialin family, plays a role in metabolic dysregulation or carotid intima-media thickness (IMT). Although no association was observed between sCD93 and IMT, sCD93 levels were significantly lower in subjects with type 2 diabetes (n = 901, mean +/- SD 156.6 +/- 40.0 ng/mL) compared with subjects without diabetes (n = 2,470, 164.1 +/- 44.8 ng/mL, P < 0.0001). Genetic variants associated with diabetes risk (DIAGRAM Consortium) did not influence sCD93 levels (individually or combined in a single nucleotide polymorphism score). In a prospective cohort, lower sCD93 levels preceded the development of diabetes. Consistent with this, a cd93-deficient mouse model (in addition to apoe deficiency) demonstrated no difference in atherosclerotic lesion development compared with apoe(-/-) cd93-sufficient littermates. However, cd93 deficient mice showed impaired glucose clearance and insulin sensitivity (compared with littermate controls) after eating a high-fat diet. The expression of cd93 was observed in pancreatic islets, and leaky vessels were apparent in cd93-deficient pancreases. We further demonstrated that stress-induced release of sCD93 is impaired by hyperglycemia. Therefore, we propose CD93 as an important component in glucometabolic regulation. PMID- 27659231 TI - Erratum. APPL1 Counteracts Obesity-Induced Vascular Insulin Resistance and Endothelial Dysfunction by Modulating the Endothelial Production of Nitric Oxide and Endothelin-1 in Mice. Diabetes 2011;60:3044-3054. PMID- 27659233 TI - A systematic review of the quality of studies on dementia prevalence in Italy. AB - BACKGROUND: Dementia, including Alzheimer's disease (AD), is one of the most burdensome medical conditions. In order to better understand the epidemiology of dementia in Italy, we conducted a systematic search of studies published between 1980 and April 2014 investigating the prevalence of dementia and AD in Italy and then evaluated the quality of the selected studies. METHODS: A systematic search was performed using PubMed/Medline and Embase to identify Italian population based studies on the prevalence of dementia among people aged >=60 years. The quality of the studies was scored according to Alzheimer's Disease International (ADI) criteria. RESULTS: Sixteen articles on the prevalence of dementia and AD in Italy were eligible and 75 % of them were published before the year 2000. Only one study was a national survey, whereas most of the studies were locally based (Northern Italy and Tuscany). Overall, the 16 studies were attributed a mean ADI quality score of 7.6 (median 7.75). CONCLUSIONS: Available studies on the prevalence of dementia and AD in Italy are generally old, of weak quality, and do not include all regions of Italy. The important limitations of the few eligible studies included in our analysis, mostly related to their heterogeneous design, make our systematic review difficult to interpret from an epidemiologic point of view. Full implementation of a Dementia National Plan is highly needed to better understand the epidemiology of the disease and monitor dementia patients. PMID- 27659235 TI - Blood Pressure Measurement in Pediatrics. PMID- 27659234 TI - A novel neuropeptide Y neuronal pathway linking energy state and reproductive behavior. AB - Animals consume energy for reproduction, as well as survival. Excess or insufficient energy investment into reproduction, respectively, threatens the survival of parents or leads to the failure of reproduction. Management of energy consumption in reproduction is important, not only for the success of the process, but also for the survival of the parents. Reproductive behaviors, such as mating and parental behavior, are indispensable for achieving each event of reproduction including gametogamy, parturition, and lactation. Therefore, reproductive behavior is one of the important factors in managing energy consumption for reproduction. Orexigenic and anorexigenic molecules in the hypothalamus have been implicated in the regulation of reproductive functions. An orexigenic neuropeptide, neuropeptide Y (NPY), has been also implicated in the regulation of both reproduction and energy state of animals. In this review, we will first summarize the neuronal mechanism for regulating reproductive functions by orexigenic and anorexigenic molecules in the hypothalamus. Second, we will focus on the NPY neuronal pathways regulating reproductive behavior in the intra- and extra-hypothalamic brain areas. We will highlight the NPY neuronal pathway from the arcuate nucleus to the dorsal raphe nucleus as a novel extra hypothalamic pathway for energy state-dependent regulation of reproductive behavior. Finally, we will propose a biological significance of the extra hypothalamic NPY neuronal pathway, which plays an important role in the associative control of feeding and reproductive behaviors. PMID- 27659236 TI - Synovial cyst of the knee: A rare case of acute sciatic neuropathy. PMID- 27659237 TI - Validation of a novel activity monitor in impaired, slow-walking, crutch supported patients. AB - BACKGROUND: A growing need in clinical practice of rehabilitation and orthopaedic medicine is for objective outcome tools to estimate physical activity. Current techniques show limited validity or are too demanding for routine clinical use. Accelerometer-based activity monitors (AMs) have shown promise for measuring physical activity in healthy people but lack validity in impaired patients. OBJECTIVES: This study aimed to validate an accelerometer-based AM in impaired, slow-walking, crutch-supported patients after total joint arthroplasty (TJA). METHODS: Shortly after TJA, patients who were safely mobilized with 2 crutches and 8 healthy participants completed a trial of different activities while wearing the AM on the lateral upper leg and being videotaped. Outcome variables (e.g., time walking, number of gait cycles, sit-stand-sit transfers) were compared to video recordings, and sensitivity, predictive value and mean percentage difference (MPD) values were calculated. RESULTS: We included 40 patients (mean age: 65+/-9 years; mean BMI: 30+/-6kg/m2; male:female ratio: 18:22) and 8 healthy participants (mean age: 49+/-20 years; mean BMI: 23+/ 0.7kg/m2; male:female ratio: 5:3). The AM showed excellent sensitivity (>95%) and predictive value (>95%) in identifying activities (e.g., walking, sitting, resting) and detecting the number of gait cycles and sit-stand-sit transfers (mean percentage difference: +/-2%). Detection of number of steps ascending and descending stairs and cadence was more difficult but still showed good results (mean percentage difference: +/-7%). CONCLUSIONS: This is the first validation study to assess physical activity with an AM in impaired, slow-walking, crutch supported patients. The AM was a valid tool for measuring physical activity in these patients. The tool may help in evaluating and optimizing rehabilitation programs for patients after TJA, those recovering from stroke or chronic impaired patients. PMID- 27659238 TI - Classifying amygdala kindling stages using quantitative assessments of extracellular recording of EEG in rats. AB - PURPOSE: Determining different seizure stage specific features in a kindling model is a crucial step in developing efficient objective techniques for early prediction and treatment of seizures. This study identified and categorized kindling stages based on their electrophysiological features through processing extracellular field potentials of Amygdala rapid kindling. METHODS: Thirteen Wistar rats (200+/-10g) were divided into 2 groups including kindle (n=7) and sham (n=6) and respectively underwent an amygdala rapid kindling and placebo stimulation. EEG signals in each stage were classified into 7 bands: delta (0 4Hz), theta (4-8Hz), alpha (8-12Hz), low beta (12-16Hz), mid beta (16-20Hz), high beta (20-28Hz) and gamma (28-40Hz). Spectral power and power of sub bands of stage 3 (localized seizure stage (SS)) and stages 4 and 5 (generalized SSs) were compared between kindling and sham groups. RESULT: Spectral analyses showed larger spikes in delta and theta subbands in the stages of 3, 4, and 5 of kindling, compared with sham animals. Generalized SSs contained more spikes than the localized SS in the kindling. Kindling process was accompanied by reduction in high beta and gamma oscillations and increase in delta sub band power which were significant in the generalized SSs. The theta/alpha ratio in the localized SS was higher than the generalized SSs and sham group, but the difference with the sham group was statistically significant. CONCLUSION: Our results showed that reduced high beta and gamma and increased delta oscillations power are associated with behavioral seizure progression. PMID- 27659239 TI - Benign Metastasizing Leiomyoma. AB - Benign metastasizing leiomyoma is a rare diagnosis in women with history of uterine leiomyomata. Distant metastasis may occur anywhere but is most commonly seen to the lungs. The age of presentation is often young to mid age, with patients often having a history of hysterectomy or myomectomy for uterine leiomyomata. The clinical course of these patients is most often indolent. However, the size and number of nodules can result in pulmonary symptoms. Differentiating benign metastasizing leiomyoma from malignant metastatic disease, including from leiomyosarcoma, is important to avoid unnecessary procedures or delayed treatment. The treatment with hormonal suppression is often successful for decreasing the size of lesions and alleviating pulmonary symptoms. PMID- 27659240 TI - Bias in the reporting of harms in clinical trials of second-generation antidepressants for depression and anxiety: A meta-analysis. AB - Previous research has shown that reporting bias has inflated the apparent efficacy of antidepressants. We investigated whether apparent safety was also affected. We included 133 trials, involving 31,296 patients, of second-generation antidepressants for the treatment of major depressive disorder (MDD) or anxiety disorders, obtained from Food and Drug Administration (FDA) reviews. We extracted data on overall discontinuation, discontinuation due to adverse events, and serious adverse events (SAEs). Meta-analysis was used to compare discontinuation rates between FDA reviews and matching journal articles, while SAEs were compared qualitatively. The odds ratio for overall discontinuation, comparing drug to placebo, was 1.0 for both sources, while that for discontinuation due to adverse events was 2.4 for both sources. Seventy-seven of 97 (79%) journal articles provided incomplete information on SAEs; sixty-one (63%) articles made no mention of SAEs at all. Of 21 articles which could be compared to the FDA, only 6 (29%) had full reporting without discrepancies. Nine (43%) articles reported a discrepant number of SAEs. Descriptions were absent or discrepant in 6 (29%) additional articles, even for important SAEs such as suicide attempts. In conclusion, reporting bias has not affected average discontinuation rates over trials. However, SAE reporting is not only very poor, with over half of articles failing to discuss SAEs altogether, but discrepancies between the FDA and articles were common and often led to a more favorable drug-placebo comparison. These findings suggest that journal articles are an unreliable source of data on SAEs in antidepressant trials. PMID- 27659242 TI - All-Arthroscopic Suprapectoral Versus Open Subpectoral Tenodesis of the Long Head of the Biceps Brachii Without the Use of Interference Screws. AB - PURPOSE: To compare patient-reported outcomes and healing rates after open subpectoral and all-arthroscopic suprapectoral biceps tenodesis without the use of interference screws in patients with more than 2 years of follow-up. METHODS: Patients with at least 2 years of follow-up who underwent open subpectoral biceps tenodesis or all-arthroscopic suprapectoral biceps tenodesis without concomitant rotator cuff repair, labral repair, or Mumford procedure were considered for enrollment in the study. They were evaluated for visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, and satisfaction with function and biceps contour. Ultrasonography was performed to evaluate the integrity of the tenodesis site and measure biceps muscle diameters on each arm. RESULTS: Forty-nine patients were eligible for our study and of these, 38 were able to participate. Twenty-three patients had open subpectoral biceps tenodesis and 15 received all-arthroscopic suprapectoral biceps tenodesis. The average follow-up time was 4.5 years (range 2-9.1 years). There were no significant differences in anterior shoulder pain VAS, ASES scores, or satisfaction rates. The average anterior shoulder VAS was 0.7 +/- 1.1 for the open group and 0.9 +/- 1.8 for the arthroscopic group (P = .74). The mean ASES score for the open group was 90.6 +/- 11.4 and 91.4 +/- 13.9 for the arthroscopic group (P = .69). All patients had an intact tenodesis site on ultrasonography and the ratio of operative to nonoperative biceps diameters was 100.2% +/- 12.8% for the open group and 99.1% +/- 10.8% for the arthroscopic group (P = .66). There were no infections and no brachial plexus injuries in either group. CONCLUSIONS: Open subpectoral biceps tenodesis and all-arthroscopic suprapectoral biceps tenodesis are both successful surgeries with consistently positive outcomes. Tenodesis can be performed in either location without interference screw fixation with durable, reliable results. LEVEL OF EVIDENCE: Level III, retrospective comparative trial. PMID- 27659241 TI - Cholesterol remnants and triglycerides are associated with decreased myocardial function in patients with type 2 diabetes. AB - BACKGROUND: Recently, genetic studies have suggested a causal relationship between cholesterol remnants and ischemic heart disease. We aimed to determine whether cholesterol remnants and its marker, triglyceride levels, are associated with cardiac function as determined by sensitive echocardiographic measures in a population of patients with type 2 diabetes. METHODS: Comprehensive echocardiography including 2D-speckle tracking echocardiography was performed on a representative sample of 924 patients with type 2 diabetes-730 of whom were treated with statins. These were recruited from two large secondary care centers. RESULTS: In multivariable analyses, triglycerides and cholesterol remnants were not associated with left ventricular ejection fraction, but with subtle measures of systolic function, including global longitudinal strain by speckle tracking and longitudinal displacement by tissue Doppler echocardiography: global longitudinal strain [0.33 % (0.14), p = 0.02 per doubling in cholesterol remnants and 0.28 % (0.13), p = 0.03 per doubling in triglyceride levels] and with longitudinal displacement [-0.25 mm (0.10), p = 0.01 per doubling in cholesterol remnants and -0.25 mm (0.09), p = 0.005 per doubling in triglyceride levels]. Subgroup analyses of patients receiving statin therapy and patients without known heart disease revealed similar results, but the association was not present in patients with known heart disease. CONCLUSION: In patients with type 2 diabetes, subtle decrease in left ventricular function is present with increasing levels of cholesterol remnants and triglyceride levels indicating an effect of these on cardiac function that is not detectable by conventional echocardiography. PMID- 27659243 TI - Recombination-based generation of the agroinfectious clones of Peanut stunt virus. AB - Full-length cDNA clones of Peanut stunt virus strain P (PSV-P) were constructed and introduced into Nicotiana benthamiana plants via Agrobacterium tumefaciens. The cDNA fragments corresponding to three PSV genomic RNAs and satellite RNA were cloned into pGreen binary vector between Cauliflower mosaic virus (CaMV) 35S promoter and nopaline synthase (NOS) terminator employing seamless recombinational cloning system. The plasmids were delivered into A. tumefaciens, followed by infiltration of hosts plants. The typical symptoms on systemic leaves of infected plants similar to those of wild-type PSV-P were observed. The presence of the virus was confirmed by means of RT-PCR and Western blotting. Re inoculation to N. benthamiana, Phaseolus vulgaris, and Pisum sativum resulted in analogous results. Generation of infectious clones of PSV-P enables studies on virus-host interaction as well as revealing viral genes functions. PMID- 27659244 TI - Construction of stabilized and tagged foot-and-mouth disease virus. AB - Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease that affects cloven-hoofed animals worldwide. Construction and purification of stable antigen for vaccine are necessary but technically difficult and laborious. Here, we have tried to investigate an alternative method by inserting a hexa-histidine tag (6xHIS) in the VP1 C-terminal for easy purification and replacing two amino acids of VP1/VP2 to enhance the stability of the capsid of the FMD virus (FMDV) Asia1/MOG/05. In addition, infectious 6xHIS tagged stable (S/T) FMDVs were maintained under acidic conditions (pH 6.0) and were readily purified from small-scale cultures using a commercial metal-affinity column. The groups vaccinated with the S/T FMDV antigen showed complete protection comparing to low survival rate in the group vaccinated with non-S/T FMDV against lethal challenge with Asia1 Shamir in mice. Therefore, the present findings indicate that the stabilized and tagged antigen offers an alternative to using the current methods for antigen purification and enhancement of stability and has potential for the development of a new FMD vaccine. PMID- 27659246 TI - Platform for determining the inhibition profile of neuraminidase inhibitors in an influenza virus N1 background. AB - Efforts to develop novel neuraminidase inhibitors (NAIs) for the treatment of influenza are ongoing. Novel NAIs should in particular be also effective against seasonal and/or pandemic N1 that carry a H274Y or N294S substitution (N2 numbering), which are most commonly linked to oseltamivir resistance. Here we report a platform for profiling the efficacy of novel NAIs in the N1 genetic background of influenza A virus. Employing reverse genetics, a set of influenza virus variants containing an amino acid substitution associated with oseltamivir resistance in N1 isolates (H274Y, N294S, Y155H or Q136L) was generated. In parallel, so far unreported mutations of I427 (I427Q and I427M) were investigated. These possibly interfere with the side chain orientation of R371 and alter the binding affinity of most relevant NAIs. The profiling platform was validated with both oseltamivir and zanamivir and exemplarily applied to three analogs with differing decorations at positions 4 and 5. Besides confirming the inhibition profile of zanamivir and oseltamivir, the distinct effect of I427Q/M on the activity of both NAIs was shown. For 5-amidino and 5-guanidino analogs of oseltamivir a significantly stronger inhibition of virus variants carrying a NA H274Y was confirmed, and additionally shown for NA-N294S and NA-Y155H substitutions as compared to the parent compound. Hence, the herein presented profiling platform is a valid tool for defining the inhibition profile of novel NAIs in the N1 background. PMID- 27659245 TI - Direct typing of Canine parvovirus (CPV) from infected dog faeces by rapid mini sequencing technique. AB - Canine parvovirus (CPV) is a non-enveloped single stranded DNA virus with an icosahedral capsid. Mini-sequencing based CPV typing was developed earlier to detect and differentiate all the CPV types and FPV in a single reaction. This technique was further evaluated in the present study by performing the mini sequencing directly from fecal samples which avoided tedious virus isolation steps by cell culture system. Fecal swab samples were collected from 84 dogs with enteritis symptoms, suggestive of parvoviral infection from different locations across India. Seventy six of these samples were positive by PCR; the subsequent mini-sequencing reaction typed 74 of them as type 2a virus, and 2 samples as type 2b. Additionally, 25 of the positive samples were typed by cycle sequencing of PCR products. Direct CPV typing from fecal samples using mini-sequencing showed 100% correlation with CPV typing by cycle sequencing. Moreover, CPV typing was achieved by mini-sequencing even with faintly positive PCR amplicons which was not possible by cycle sequencing. Therefore, the mini-sequencing technique is recommended for regular epidemiological follow up of CPV types, since the technique is rapid, highly sensitive and high capacity method for CPV typing. PMID- 27659247 TI - Care ethics. A new bioethical approach to humanize the ICU. PMID- 27659248 TI - Consensus statement on the management of dyslipidaemias in adults. PMID- 27659249 TI - In Situ Intestinal Perfusion in Rodents: Future Perspectives for Application on Absorption Studies and Classification of Drugs. AB - BACKGROUND: In 1995, the Biopharmaceutics Classification System (BCS) was proposed by Amidon and colleagues as a tool that considers two important parameters regarding drugs: solubility and permeability. Since then, several methods for solubility and permeability studies have been developed for drug delivery and absorption prediction. In recent years, permeability has gained a great highlight and the interaction between a molecule and a biological membrane is not enough to predict the in vivo behavior of a compound. METHOD: Thus, different methods for permeability assessment are currently used for mechanistic studies including involvement of carriers and several transport pathways. Furthermore, the investigation regarding metabolism has been a focus in recent researches. Based on this idea, Wu and Benet proposed a new tool called Biopharmaceutics Drug Disposition Classification System (BDDCS), where drugs are classified into four classes considering their solubility and metabolism. RESULTS: Among several methods for permeability studies, the in situ intestinal perfusion is considered the closest to in vivo conditions due advantages as intact blood supply and innervation. CONCLUSION: This review presents the in situ intestinal perfusion model and its application for permeability/ transport studies of drugs and intestinal metabolism. Also, this paper discusses about how the in situ perfusion studies can be used for classification of drugs and the future perspectives for in vivo absorption prediction. PMID- 27659251 TI - Searching for Novel Janus Kinase-2 Inhibitors Using a Combination of Pharmacophore Modeling, 3D-QSAR Studies and Virtual Screening. AB - The Janus kinases (JAKs) play a pivotal role in cytokine receptor signaling pathways via activation of downstream signal transducers and activators of transcription (STAT) pathway. Intracellular pathways that include JAKs are critical to immune cell activation and pro-inflammatory cytokine production. Selective inhibitors of JAKs are potentially disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis (RA). Each of the four members of the JAK family plays an individual role in the oncogenesis of the immune system, and therefore, the development of potent and specific inhibitors for each member is needed. Although there is a high sequence homology and structural identity of JAK1 and JAK2, such as a very similar binding mode of inhibitors at the ATPbinding site of enzymes, obvious differences surrounding the JAK1 and JAK2 ATP binding sites provide a platform for the rational design of JAK2- and JAK1 specific inhibitors. In the present study, a dataset of 33 compounds characterized by a common scaffold of 2-amino-[1,2,4]triazolo[1,5-α]pyridine with well-defined in vitro activity values was computationally explored. Most of the compounds included in the dataset had higher ligand efficiency against JAK2 than JAK1. To improve further the selectivity of these triazolopyridines, Common Pharmacophore Hypotheses (CPHs) were generated and 3D-QSAR studies were carried out on them, in order to comprehend on the molecular features responsible for their selectivity. The proposed computational approach was applied in order to perform an in silico database virtual screening study with the aim to discover novel potent and selective JAK2 inhibitors. PMID- 27659250 TI - A Review of Three Commonly Used Herbs Which Enhance Memory and New Evidences Which Show Their Combination Could Improve Memory in Young Animals. AB - BACKGROUND: This review looks into the herbs Gingko biloba, Polygala tenuifolia, and Lycii fructus for their widely studied neuroprotective properties. In particular, we investigated memory enhancing effect of these herbs, and their potential synergetic effect on memory with new data. Sixmonth treated mice demonstrated shorter escape latency in water maze and shorter arrival time in a consolidated memory task. Immunochemistry showed evident increase in superoxide dismutase activities in the prefrontal cortex, implying protection against free radicals during aging. Discrete increase of catecholaminergic neurons was found in the prefrontal cortex, hippocampus, corpus striatum, and midbrain, suggesting better memory and better control on mood and behavior. Necrotic cells in the brain decreased as indicated by immunocytochemistry of lactic dehydrogenase. Terminal deoxynucleotidyl transferase dUTP nick end labeling showed no apoptotic cells in most brain areas in high dose group. Biochemistry revealed increase of dopaminergic cells in treatment groups at prefrontal cortex, and in the hippocampus and cerebellum of the high dose group. Most 6-month groups showed increase of serotonin in all three areas. For the high dose group, GABA increased in the hippocampus but not prefrontal cortex, which would help induce sleep at night. Protein kinase C increased in most groups at prefrontal cortex, hippocampus and cerebellum, signifying increase of possible signal transduction pathways for memory or other nervous activations. CONCLUSION: Our results intimate that the interaction of the three herbs exerts beneficial effects on memory, associated cognitive function, and necrosis. Future investigations based on the present data shall aid development of clinically relevant medication. PMID- 27659252 TI - Asthma is associated with reduced fibrinolytic activity, abnormal clot architecture, and decreased clot retraction rate. AB - The aim of this study was to assess whether steroid-naive asthma modulates hemostasis. We evaluated the clot retraction rate (CRR), fibrinolysis rate (FR), clot density (CD) (by confocal microscopy), plasma levels of plasminogen activator inhibitor (PAI-1), and factor XIII (FXIII), NO in exhaled breath (FENO ), spirometry (FEV1 ) and eosinophil count (EOS) in 36 patients with allergic, steroid-naive asthma and in 34 healthy controls. We observed significantly (P < 0.001) reduced CRR, FR, and FEV1 and increased FENO , EOS, PAI-1, FXIII, and CD in patients with asthma compared with controls. In patients with asthma, FR negatively correlated with CD, FXIII, PAI-1, FENO , and EOS and positively with FEV1 . FXIII positively correlated with CD. Clot retraction rate negatively correlated with FENO and positively with FEV1 (all P < 0.001). These novel findings suggest that asthma itself is associated with decreased CRR and reduced fibrinolytic potential resulting from alterations in clot architecture and elevated levels of plasma FXIII and PAI-1. PMID- 27659253 TI - Topically Applied Hsp90 Blocker 17AAG Inhibits Autoantibody-Mediated Blister Inducing Cutaneous Inflammation. AB - Cell stress-inducible Hsp90 has been recognized as key player in mediating inflammatory responses. Although its systemic blockade was successfully used to treat autoimmune diseases in preclinical models, efficacy of a topical route of Hsp90 inhibitor administration has so far not been evaluated in chronic inflammatory and autoimmune-mediated dermatoses. Here, effects of the Hsp90 blocker 17-allylamino-demethoxygeldanamycin (17AAG) applied topically to the skin were determined in experimental inflammatory epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-induced blistering skin disease. Topical 17AAG ameliorated clinical disease severity when given before or during the occurrence of skin lesions without causing cutaneous or systemic toxicity in mice with antibody transfer- and immunization-induced EBA. In both EBA models and in the setting of locally induced inflammation, topical 17AAG treatment was associated with (i) reduced neutrophilic infiltrates, (ii) decreased NF-kappaB activation, (iii) lowered expression of matrix metalloproteinases and Flii, and (iv) induction of anti-inflammatory Hsp70 in the skin. Our results suggest that topical delivery of Hsp90 antagonists, offering the benefit of a reduced risk of systemic adverse effects of Hsp90 inhibition, may be useful for the control of EBA and possibly other related inflammatory skin disorders. PMID- 27659254 TI - Recycling pacemakers and defibrillators: A humanitarian cause-Is it feasible? PMID- 27659256 TI - A 24-year-old man with an irregular pulse. PMID- 27659255 TI - "Wide-narrow-wide" QRS complex tachycardia: What is the mechanism? PMID- 27659257 TI - The Australian laparoscopic non robotic radical prostatectomy experience - analysis of 2943 cases (USANZ supplement). AB - OBJECTIVES: To analyse the Australian experience of high-volume Fellowship trained Laparoscopic Radical Prostatectomy (LRP) surgeons. MATERIALS AND METHODS: 2943 LRP cases were performed by nine Australian surgeons. The inclusion criteria were a prospectively collected database with a minimum of 100 consecutive LRP cases. The surgeons' LRP experience commenced at various times from July 2003 to September 2009. Data were analysed for demographic, peri-operative, oncological and functional outcomes. RESULTS: The mean age of patients were 61.5 years and mean preoperative PSA 7.4 ng/ml. Mean operating time was 168 minutes with conversion to open surgery in 0.5% and a blood transfusion rate of 1.1%. Overall mean length of stay was 2.5 days. 73.6% of pathological specimens were pT2 and 86.3% had Gleason Score >7. Overall positive surgical margins (PSM) occurred in 15.9% with pT2 PSM 9.8%, pT3a PSM 30.8% and pT3b PSM 39.2%. Mean urinary continence at 12 months was 91.4% (data available from five surgeons). Mean 12 months potency after bilateral nerve spare was 47.2% (data available from four surgeons). Biochemical recurrence occurred in 10.6% (mean follow up 17 months). CONCLUSION: The Australian experience of Fellowship trained surgeons performing LRP demonstrates favourable peri-operative, oncological and functional outcomes in comparison to published data for open, laparoscopic and robotic assisted radical prostatectomy. In our Australian centres, LRP remains an acceptable minimally invasive surgical treatment for prostate cancer despite the increasing use of robotic assisted surgery. PMID- 27659258 TI - A comparative ethnobotany of Khevsureti, Samtskhe-Javakheti, Tusheti, Svaneti, and Racha-Lechkhumi, Republic of Georgia (Sakartvelo), Caucasus. AB - BACKGROUND: The Republic of Georgia (Sakartvelo in Georgian language) is part of the Caucasus biodiversity hotspot, and human agricultural plant use dates bat at least 6000 years. However, little ethnobiological research has been published from the region since the 1940s. Given the lack of recent research in the region, the present study we report on plant uses in Skartvelo (Republic of Georgia), Caucasus. We hypothesized that, (1) given the long tradition of plant use, and the isolation under Soviet rule, plant use both based on homegardens and wild harvesting would be more pronounced in Georgia than in the wiser region, (2) the Soviet occupation would have had broad influence on plant use, and (3) there would still be incidence of knowledge loss despite wide plant use. METHODS: Fieldwork was conducted in Khevsureti, Samtskhe-Javakheti, Tusheti, Svaneti, and Racha in July-August 2013, July-August 2014, and September-October 2015. Interviews using semi-structured questionnaires were conducted with 170 participants (80 women and 90 men) after obtaining their oral prior informed consent. All interviews were carried out in the participants' homes and gardens by native speakers of Georgian and its local dialects (Svan, Tush, Khevsur, Psav), or, where participants spoke these as their native language, Armenian, Russian, or Greek. RESULTS: In the present study we encountered 480 plant species belonging to 249 genera of 95 families being used in the research region. The highest number of species and of unique species were reported from the remote Tusheti-Khevsureti region. Informant consensus and number of use reports were highest for each region in the food and medicinal use categories. Of the 480 plants being used in the research region 282 species were exclusively wild harvested, 103 were grown in homegardens, and 84 were both grown in gardens and sourced in the wild. CONCLUSIONS: Plant species, and uses, found in our study, both for Georgia in general, as well as for its regions, showed clear relations to the wider Caucasus - Asia Minor - Balkans cultural complex. However, plant use in Georgia was much more diverse than reported in other studies from Eurasia. PMID- 27659259 TI - A Self-Assembled Sensor for Carbohydrates on the Surface of Cyclodextrin Vesicles. AB - A supramolecular carbohydrate sensor was prepared by self-assembly of unilamellar bilayer vesicles of amphiphilic beta-cyclodextrin with a boronic acid-adamantane conjugate (PBA-AD), which binds strongly to beta-cyclodextrin through host-guest interactions (Ka ~4*104 m-1 ), so the vesicle surface exhibits multiple boronic acid receptors for carbohydrates. The binding of diols to the functionalized vesicles was tested with alizarin red S (ARS) as a reporter dye by using fluorescence and UV/Vis spectroscopy. Analysis of the competitive binding of monosaccharides revealed pH-dependent (pH 7.4-10.1) binding constants in the range of 100-3000 m-1 for d-fructose and 5-400 m-1 for d-glucose. Interestingly, the self-assembled sensor showed fluorescence intensity enhanced by about fivefold and a binding affinity to the reporter dye increased by about eightfold in comparison to PBA-AD and ARS without vesicles. This is attributed to increased local concentration of ARS and PBA-AD on the surface of the vesicles. Detection of d-fructose and d-glucose was possible in the physiologically relevant range in dilute aqueous solution. PMID- 27659261 TI - Fullerenes as Anti-Aging Antioxidants. AB - Here we review fullerenes biological effects focusing on their antioxidant and anti-ageing action. A scope of various poisonous and healing properties reported in literature for fullerene and its derivatives is analyzed. The review begins with the history of fullerenes discovery and their main properties. Then we focus on the longevity and antioxidant action, including the confrontation of available experimental data and theoretical modeling of buckminsterfullerene C60. Special attention is given to our hypothesis concerning the possibility of fullerenes to act as mitochondria protonophore and various simulations of the transport of C60 and its hydroxylated and other derivatives through lipid bilayer membranes, which can account for scavenging capacity of fullerenes for reactive oxygen species and their acting as mild mitochondrial respiration uncouplers. Extension of the theoretical modeling to the mitochondria membranes and implications on the real biological systems is analyzed. Finally, we focus on the toxicity evaluation and current therapeutic usage of fullerenes. The review contains a comprehensive discussion of both papers published by 2016 and our own research results. PMID- 27659260 TI - Maximizing potential impact of experimental research into cognitive processes in health psychology: A systematic approach to material development. AB - BACKGROUND: There is an abundance of research into cognitive processing biases in clinical psychology including the potential for applying cognitive bias modification techniques to assess the causal role of biases in maintaining anxiety and depression. Within the health psychology field, there is burgeoning interest in applying these experimental methods to assess potential cognitive biases in relation to physical health conditions and health-related behaviours. Experimental research in these areas could inform theoretical development by enabling measurement of implicit cognitive processes that may underlie unhelpful illness beliefs and help drive health-related behaviours. However, to date, there has been no systematic approach to adapting existing experimental paradigms for use within physical health research. Many studies fail to report how materials were developed for the population of interest or have used untested materials developed ad hoc. The lack of protocol for developing stimuli specificity has contributed to large heterogeneity in methodologies and findings. PURPOSE: In this article, we emphasize the need for standardized methods for stimuli development and replication in experimental work, particularly as it extends beyond its original anxiety and depression scope to other physical conditions. METHOD: We briefly describe the paradigms commonly used to assess cognitive biases in attention and interpretation and then describe the steps involved in comprehensive/robust stimuli development for attention and interpretation paradigms using illustrative examples from two conditions: chronic fatigue syndrome and breast cancer. CONCLUSIONS: This article highlights the value of preforming rigorous stimuli development and provides tools to aid researchers engage in this process. We believe this work is worthwhile to establish a body of high-quality and replicable experimental research within the health psychology literature. Statement of contribution What is already known on this subject? Cognitive biases (e.g., tendencies to attend to negative information and/or interpret ambiguous information in negative ways) have a causal role in maintaining anxiety and depression. There is mixed evidence of cognitive biases in physical health conditions and chronic illness; one reason for this may be the heterogeneous stimuli used to assess attention and interpretation biases in these conditions. What does this study add? Steps for comprehensive/robust stimuli development for attention and interpretation paradigms are presented. Illustrative examples are provided from two conditions: chronic fatigue syndrome and breast cancer. We provide tools to help researchers develop condition specific materials for experimental studies. PMID- 27659262 TI - Physiological and Biochemical Mechanisms of Lifespan Regulation in Rats Kept Under Various Light Conditions. AB - BACKGROUND: The present study was aimed to identify how age-related changes in some physiological and biochemical systems are related to changes in the life span of rats with long-term pineal gland hypo- and hyperfunction induced by constant light and constant darkness, respectively. METHODS: At the age of 25 days the rats were randomly divided into 3 groups: standard light/dark regimen (LD), constant light (LL) and constant darkness (DD). Age-related Antioxidant System (AOS) changes in liver tissues, alteration of immunoreactivity in blood smears were investigated, pubescence and lifespan of the animals were determined. RESULTS: Modification of the level of melatonin synthesis induced by constant light results in interrelated rearrangements in the functioning of the investigated physiological systems. Elevated activity of the antioxidant system extends the lifespan, while at the same time slowing down pubescence and altering the morpho-functional properties of leukocytes in blood. CONCLUSION: The absence of light/dark alternation (constant light and constant darkness) affects only those physiological indices that follow the organism's circadian rhythms (Activity of Antioxidant Enzymes (AOE), levels of individual immune system cell types), whereas changes in the parameters not governed by circadian fluctuations (vitamin concentrations, pubescence, and aging) depend on the level of melatonin produced by the pineal gland. PMID- 27659264 TI - Cellular and Molecular Mechanisms of Action of Mitochondria-Targeted Antioxidants. AB - Reactive oxygen species generated in mitochondria are an important factor contributing to mitochondrial and cellular dysfunction underlying many degenerative diseases, chronic pathologies and aging. The idea of delivering antioxidant molecules to mitochondria in vivo to treat these diseases and slow aging intensively developed in the last 20 years. Derivatives of quinones covalently conjugated to a lipophilic cation (e.g., MitoQ and SkQ) were the most extensively studied mitochondria-targeted antioxidants. These compounds have now been used in a wide range of in vitro and in vivo studies, as well as in clinical trials in humans. Here, we review recent progress in this field with a special attention on molecular mechanisms of rechargeable mitochondria-targeted antioxidants. A simple hypothesis that aging results from gradual accumulation of occasional damage inflicted by ROS to DNA, proteins and lipids is apparently insufficient. More and more pieces of evidence indicate that the damage in question is programmed. Moreover, the imbalance in ROS-dependent regulatory mechanisms and compromised ROS signaling are underlying many pathologies and aging. Chain reactions of cardiolipin peroxidation initiated by mitochondrial ROS seem to play a key role in these degenerative processes. Such reactions are specifically abolished by mitochondriatargeted antioxidants. PMID- 27659263 TI - Aging and Ambiguous ROS. System Genetics Analysis. AB - Famous Free Radical Theory (FRT) of aging, the 50th year anniversary of which is celebrated in 2015 postulates a crucial role of Reactive Oxygen Species (ROS) in aging. Still it is the most robust theory of aging as mitochondria ROS production (mtROSp) correlates well with four principal ''rules" of aging being universal, endogenous, progressive, and deleterious. Vast number of experiments in different species prove mutagenic effect of ROS and their carcinogenic properties. So far, FRT stimulates the search of new pharmaceuticals with antioxidant activity. However, some recent experimental data and clinical findings render doubt to ROS as a principal senescence drivers and come in conflict with original version of FRT. Growth stimulating effects of ROS and their modest antitumor properties support these objections. One should remember that FRT is only one of the numerous theories of aging. Molecular mechanisms of senescence involve all living systems and numerous metabolic pathways which are also variable owing to the unique properties of individual genome and unique epigenetic modulations operating throughout the lifetime thus making aging a unique private matter. Universal theory of aging that incorporates and explains all known and suggested mechanisms of aging, is illusive. However, knowledge of unique peculiarities of individual genome, its feasible editing and efficient epigenetic regulation of metabolic pathways give a chance to postpone aging and extend period of active longevity. PMID- 27659265 TI - Chemical Modification of Ginsenoside on Cell Viability and Cytokine Secretion. AB - BACKGROUND: Rb1 is a ginsenoside steroid glycoside found exclusively in the plant Panax ginseng. In an earlier report, we showed that Rb1 increased cell proliferation and reduced VEGF (vascular endothelial growth factor) secretion by human retinal pigment epithelial (ARPE19) cells. OBJECTIVE: In the present study, we hypothesized that chemical modification of Rb1 changes the level of VEGF secretion by ARPE19 cells. METHOD: Three derivatives of Rb1 were chemically synthesized by hydrogenation (Rb1-H2), acetylation (Rb1-Acyl), and epoxidation (Rb1-Epoxy). Structural modifications were confirmed by 1H Nuclear Magnetic Resonance (NMR) spectra and Mass Spectrometry (MS). To test the biological activity, chemically modified compounds were added to cell culture media and incubated for 72 hours at a concentration of 250 nM at 37 degrees C. Conditioned media were collected and cells were harvested/ counted after treatment. Viable cell numbers were determined by the trypan blue dye exclusion method and VEGF levels by Enzyme-Linked Immunosorbent Assays (ELISA). RESULTS: Consistent with the prior report, results of the present study show Rb1 increased cell proliferation and decreased VEGF secretion. Similar to Rb1's effect on cell proliferation, treatment with Rb1-H2, Rb1-Acyl and Rb1-Epoxy resulted in an increase in cell numbers. In contrast to Rb1- induced decrease in VEGF secretion, treatment with Rb1-H2, Rb-Acyl and Rb1-Epoxy resulted in increased VEGF levels. CONCLUSION: Chemical modifications of the ginsenoside Rb1 significantly affect the biological activity of VEGF secretion by ARPE19 cells. Additional SAR (Structure Activity Relationship) experiments will be conducted to study the detailed mechanisms by which how specific modifications of Rb1 functional groups alter biological activities. PMID- 27659266 TI - Thyroid hormone transport across the placenta. PMID- 27659268 TI - Mucinous carcinoma of the thyroid: A case report and review of the literature. AB - We report the case of a primary mucinous carcinoma of the thyroid in a man of 74 who had a 4-cm nodule in the right lobe of the thyroid, with a solido-cystic appearance on ultrasound associated with lymph node metastases. On scintigraphy, the nodule was hot and not extinctive. The patient underwent total thyroidectomy with a ipsilateral right lymph node dissection. The immunohistochemical study showed the negativity of CK 7 and CK 20 and the positivity of thyroglobulin and TTF 1. Postoperatively the rate of blood thyroglobulin 3 months after surgery had collapsed to 0.17ng/ml. The evolution was marked by the appearance of pulmonary metastasis and the patient died 4 months after surgery. Histological study showed the presence of almas of neoplastic cells surrounded by large deposits of extracellular mucin. Primitive mucinous carcinoma of the thyroid is a rare tumor which differential diagnosis is established on the positive immunohistochemistry of thyroglobulin and TTF1 but negative for other markers. PMID- 27659267 TI - Current biomarkers of invasive sporadic pituitary adenomas. AB - Though pituitary adenomas (PA) are considered benign, some of them exhibit invasive behaviors such as recurrence and low rate of total surgical resection. Reliable prognostic biomarkers for invasive PA are highly desired; however they remain to be identified. In this review, we summarize the current controversial findings of biomarkers for invasive sporadic PA, and we discuss the possible reasons for the controversies. PMID- 27659269 TI - Identification of Pb sources using Pb isotopic compositions in the core sediments from Western Xiamen Bay, China. AB - Pb concentrations and Pb isotopic compositions (total and acid-extractable) in the core sediments collected from Western Xiamen Bay, China, were determined to investigate the Pb pollution history and trace the Pb sources. Pb concentration showed an increasing trend (from 40.3 to 64.2mgkg-1) with obvious fluctuation from 1967 to 2013, reflected by the core sediments. The enrichment factors of Pb were between 2 and 5, indicating a moderate enrichment. The relative contributions of Pb-Zn deposit and parent material to total Pb in the core sediments were 51%-62% and 38%-49%, respectively. Acid-extractable Pb isotopic signature was more sensitive than total Pb isotopic signature in identifying anthropogenic Pb sources due to the substantial variability of acid-extractable Pb isotopic ratios exhibited in the core sediments. Based on the acid-extractable Pb isotopic ratios, Pb-Zn deposit and industrial emission were regarded as the main anthropogenic Pb contributors. PMID- 27659270 TI - Improving optimization efficiency for the total pollutant load allocation in large two-dimensional water areas: Bohai Sea (China) case study. AB - The total pollutant load allocation (TPLA) can be transformed into an optimization problem with regards to water quality constraints. The optimization calculation may become very time consuming when the number of water quality constraint equations is great. A Trial and Error Method (TEM) to remove the redundant points was first introduced through iterative calculations under structure and non-structure model grids. The TEM was applied for the TPLA in the Bohai Sea in China. The calculation time was reduced to about 2min under the condition that 103,433 model grids met the water quality standards. In the best case, the optimization efficiency was improved by 98.9%. The allocation results showed that approximately 90% of total nitrogen (TN) load should be reduced in the 56 pollution sources around the Bohai Sea; of these values, roughly 85% of the reduction could come from 10 pollution sources. PMID- 27659271 TI - Trophic transfer of toxic elements in the estuarine invertebrate and fish food web of Daliao River, Liaodong Bay, China. AB - In order to study element accumulation and trophic transfer in the food web, sixteen benthic invertebrate species and nine fish species were collected from the Daliao River estuary for analysis of toxic elements and nitrogen stable isotope in the muscle tissue. The concentrations ranged between 1.44-17.98, 0.01 9.30, 0.17-36.15, 0.7-145.4, 0.01-0.33, 0.14-14.88, 0.10-2.51, 0.02-0.14, and 19.3-221.1mgkg-1 for As, Cd, Cu, Hg, Ni, Pb, Sb, and Zn, respectively. As, Cd, Cu, and Zn were significantly higher in the benthic invertebrates than in fish, whereas Hg and Sb were significantly lower. In addition, the benthic invertebrates were characterized by the highest bioaccumulation factor (BAF) for Cd, whereas the fish were characterized by the highest BAF for Hg. A significant decrease in Cd, Cr, Cu, and Ni levels, and a significant increase in Hg and Sb levels were observed with increasing trophic levels. PMID- 27659272 TI - Biocompatible poly(vinyl alcohol) nanoparticle-based binary blends for oil spill control. AB - In the current study, biocompatible and biodegradable blends based on poly(vinyl alcohol) nanoparticles - PVAn mixed with either chitosan (Ch) or starch (St) - were prepared and investigated as nanoabsorbents for oil elimination from wastewater. The use of water/dimethyl sulfoxide (DMSO) as a mixed solvent is the key factor for preparing aggregated PVAn, which is further mixed with Ch or St. Nanoblends were applied as oil absorbents, and the results showed that PVAn/St possess high adsorption capacity than PVAn/Ch and PVAn. The maximum sorption capacities (qg/g) of the PVAn/Ch sorbents for hydraulic oil, kerosene, and toluene were 33.6, 73.96, and 93.1g/g, respectively. The absorbed oil could be rapidly recovered by simple mechanical squeezing and reused without any other modification. The blends showed excellent reusability and could be reused for at least 10 times with minimal losses. The current study demonstrates the application of these blends as an ideal alternative sorbent for oil spillage cleanup. PMID- 27659273 TI - Risk assessment for marine spills along European coastlines. AB - A marine-spill risk index is proposed to measure and compare the relative vulnerability of coastal regions to marine spills in European waters. It is applied to 301 spills in European waters between 1970 and 2014 for 429 Eurostat territorial units and 156 regions in Europe's coasts. The results show a high heterogeneity among European coastal regions with areas, predominantly on the Atlantic coast, with high marine-spill risks. In particular, UK coasts are markedly affected as there are only five non-British coastal territories within the first 25 territorial units most at risk from marine spills. Across countries, European Atlantic countries face highest risks versus coastal countries on other European waters that are relatively safer. The index also shows a tendency of sea currents to have positive dispersal effects leading to smaller risks rather than otherwise. The index may help to design protection policies and reduce the vulnerability of sensitive resources. PMID- 27659274 TI - Citizen science data reveal ecological, historical and evolutionary factors shaping interactions between woody hosts and wood-inhabiting fungi. AB - Woody plants host diverse communities of associated organisms, including wood inhabiting fungi. In this group, host effects on species richness and interaction network structure are not well understood, especially not at large geographical scales. We investigated ecological, historical and evolutionary determinants of fungal species richness and network modularity, that is, subcommunity structure, across woody hosts in Denmark, using a citizen science data set comprising > 80 000 records of > 1000 fungal species on 91 genera of woody plants. Fungal species richness was positively related to host size, wood pH, and the number of species in the host genus, with limited influence of host frequency and host history, that is, time since host establishment in the area. Modularity patterns were unaffected by host history, but largely reflected host phylogeny. Notably, fungal communities differed substantially between angiosperm and gymnosperm hosts. Host traits and evolutionary history appear to be more important than host frequency and recent history in structuring interactions between hosts and wood-inhabiting fungi. High wood acidity appears to act as a stress factor reducing fungal species richness, while large host size, providing increased niche diversity, enhances it. In some fungal groups that are known to interact with live host cells in the establishment phase, host selectivity is common, causing a modular community structure. PMID- 27659275 TI - Risk Perceptions of Little Cigar and Cigarillo Smoking Among Adult Current Cigarette Smokers. AB - Introduction: Few studies have examined the perceptions of risk of little cigar and cigarillo (LCC) smoking among cigarette smokers, which is important for expanding regulatory policies and developing prevention programs. We examined current cigarette smokers' perceived harm of LCC smoking, and determined whether these perceptions were associated with susceptibility and intention to continue smoking LCCs. Methods: Data were from the 2014 Tobacco Products and Risk Perceptions Survey of a probability sample of 5717 US adults. Data were analyzed for a subsample of 1191 current cigarette smokers who were stratified into three groups: (1) dual current cigarette smokers who had ever used LCCs, (2) current smokers susceptible to LCC smoking, and (3) current smokers who were not susceptible to LCC smoking. Results: Overall, 47.2% of participants were dual smokers, 12.7% were susceptible to LCC smoking, and 40.1% were not susceptible. Perceptions of risk of LCCs varied across the groups. Dual smokers were more likely to perceive that daily LCC smoking is "very risky" (OR = 1.64, 95% CI = 1.08, 2.41) while occasional LCC smoking is only "somewhat risky" (OR = 1.71, 95% CI = 1.02, 2.87). Of the dual smokers, 20.7% intended to continue smoking LCCs in the future. Perceptions of addiction and risk of daily LCC smoking significantly predicted intention to continue LCC smoking. Addiction perceptions also significantly predicted susceptibility to initiate LCC smoking. Conclusions: Perceptions about harms from and addiction to LCCs could predict future LCC smoking. Health communication campaigns need to address the harms of LCCs. Implications: Our data suggest that perceptions of risk about the addictiveness of LCCs and frequency of use are important determinants of the LCC smoking susceptibility among some cigarette smokers and intended continued use among cigarette smokers with a history of LCC use. Health communication campaigns should address misperceptions related to LCCs. PMID- 27659276 TI - Effect of 5% benzocaine gel on relieving pain caused by fixed orthodontic appliance activation. A double-blind randomized controlled trial. AB - AIM: To compare the effectiveness of 5% benzocaine gel and placebo gel on reducing pain caused by fixed orthodontic appliance activation. SETTING AND SAMPLE POPULATION: Thirty subjects (15-25 years) undergoing fixed orthodontics. METHODS AND MATERIALS: A randomized, double-blind, placebo-controlled and cross over clinical trial study was conducted. Subjects were asked to apply a placebo gel and 5% benzocaine gel, exchangeable in two consecutive appointments, twice a day for 3 days and mark their level of pain on a VAS scale. The pain severity was evaluated by means of Mann-Whitney U-test for comparing two gel groups, Kruskal Wallis nonparametric test for overall differences and post hoc test of Dunnett for paired multiple comparisons. p-value was assigned <0.05. RESULTS: The overall mean value of pain intensity for benzocaine and placebo gels was 0.89 and 1.15, respectively. The Mann-Whitney U-test indicated that there was no significant difference between overall pain in both groups (mean difference = 0.258 p ? 0.21). For both groups, pain intensity was significantly lower at 2, 6 and 24 h compared with pain experienced at days 2, 3 and 7. CONCLUSION: Benzocaine gel caused a decrease in pain perception at 2 h compared with placebo gel. Peak pain intensity was at 2 h for placebo gel and at 6 h for benzocaine gel, followed by a decline in pain perception from that point to day 7 for both gels. PMID- 27659277 TI - Caring Through Web-Based Communication: A Qualitative Evaluation of a Nursing Intervention to Create Holistic Well-Being Among Patients With Hematological Disease. AB - PURPOSE: To examine how written communication between patients with hematological diseases and a nurse within a web-based communication service can be caring. DESIGN: The study is based on qualitative deductive content analysis of 109 written messages between 10 patients and a responding nurse. The evaluated nursing intervention is a web-based communication service where patients could request support from a responding nurse during 2 months of use. A structured theoretical matrix based on Swanson's theory of caring including compassion, competence, and upholding trust is used for the analysis. FINDINGS: Nursing compassion emerges when patients share personal matters and the nurse has an opportunity to explicitly display genuine interest and understanding. Nursing competence is required when patients ask for or are in need of information, advice, and emotional support. The nurse can uphold trust when compassion and competence are exhibited and patients share their innermost feelings. CONCLUSIONS: Web-based communication has the potential to contribute to holistic well-being according to Swanson's theory of caring. The written word lasts, can be read repeatedly, and in connection with writing there is time for reflection. However, the lack of nonverbal cues makes it important that the nurse answers in a fully accurate and explicitly caring way. PMID- 27659278 TI - Optical coherence tomography angiography in age-related macular degeneration: persistence of vascular network in quiescent choroidal neovascularization. PMID- 27659279 TI - Antibacterial activity of a modified unfilled resin containing a novel polymerizable quaternary ammonium salt MAE-HB. AB - Resins with strong and long-lasting antibacterial properties are critical for the prevention of secondary dental caries. In this study, we evaluated the antibacterial effect and the underlying mechanism of action of an unfilled resin incorporating 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) against Streptococcus mutans UA159 (S. mutans UA159). MAE-HB was added into unfilled resin at 10 mass%, and unfilled resin without MAE-HB served as the control. Bacterial growth was inhibited on 10%-MAE-HB unfilled resin compared with the control at 1 d, 7 d, 30 d, or 180 d (P < 0.05). The growth inhibitory effect was independent of the incubation time (P > 0.05). No significant differences in the antibacterial activities of eluents from control versus 10% MAE-HB unfilled resins were observed at any time point (P > 0.05). The number of bacteria attached to 10%-MAE-HB unfilled resin was considerably lower than that to control. Fe-SEM and CLSM showed that 10%-MAE-HB unfilled resin disturbed the integrity of bacterial cells. Expression of the bacterial glucosyltransferases, gtfB and gtfC, was lower on 10%-MAE-HB unfilled resin compared to that on control (P < 0.05). These data indicate that incorporation of MAE-HB confers unfilled resin with strong and long-lasting antibacterial effects against S. mutans. PMID- 27659281 TI - Molecular mechanisms of HLA class I-mediated immune evasion of human tumors and their role in resistance to immunotherapies. AB - Although the human immune system can recognize and eradicate tumor cells, tumors have also been shown to develop different strategies to escape immune surveillance, which has been described for the first time in different mouse models. The evasion of immune recognition was often associated with a poor prognosis and reduced survival of patients. During the last years the molecular mechanisms, which protect tumor cells from this immune attack, have been identified and appear to be more complex than initially expected. However, next to the composition of cellular, soluble and physical components of the tumor microenvironment, the tumor cells changes to limit immune responses. Of particular importance are classical and non-classical human leukocyte antigen (HLA) class I antigens, which often showed a deregulated expression in cancers of distinct origin. Furthermore, HLA class I abnormalities were linked to defects in the interferon signaling, which have both been shown to be essential for mounting immune responses and are involved in resistances to T cell-based immunotherapies. Therefore this review summarizes the expression, regulation, function and clinical relevance of HLA class I antigens in association with the interferon signal transduction pathway and its role in adaptive resistances to immunotherapies. PMID- 27659282 TI - Intraoperative navigation in complex head and neck resections: indications and limits. AB - PURPOSE: The surgical removal of head and neck tumors often represents a highly complex surgery. The three-dimensionality and the anatomy of the head and neck area make sometimes difficult a correct intraoperative orientation and the obtaining of an adequate oncological safety. In the present pilot study, the authors propose a protocol of application of intraoperative navigation in the resection of head and neck tumors. The purpose is to develop a methodology that can be helpful to ensure oncologic free margins of resection and to facilitate the orientation of the specimen by pathologists. MATERIALS AND METHODS: A sample of 16 patients with head and neck tumors was selected, and they were differentiated into two groups: a "study group" treated with CT computer-assisted surgery and a "control group" surgically treated without the use of technology. The following data were analyzed: operative and pre-surgical planning times, issues related to the use of the technologies, respect of the planned landmarks, description and orientation of the surgical specimen and distance of the tumor from the margins of resection. RESULTS: In the "study group" were noticed a reduced rate of errors in the specimen orientation and an increased distance of the tumor from the margins of resection. Similar operative times were observed in both groups. CONCLUSIONS: Intraoperative navigation resulted to be a reliable method to improve oncological safety in a selected group of patients. PMID- 27659283 TI - Automated liver segmentation from a postmortem CT scan based on a statistical shape model. AB - PURPOSE: Automated liver segmentation from a postmortem computed tomography (PMCT) volume is a challenging problem owing to the large deformation and intensity changes caused by severe pathology and/or postmortem changes. This paper addresses this problem by a novel segmentation algorithm using a statistical shape model (SSM) for a postmortem liver. METHODS: The location and shape parameters of a liver are directly estimated from a given volume by the proposed SSM-guided expectation-maximization (EM) algorithm without any spatial standardization that might fail owing to the large deformation and intensity changes. The estimated location and shape parameters are then used as a constraint of the subsequent fine segmentation process based on graph cuts. Algorithms with eight different SSMs were trained using 144 in vivo and 32 postmortem livers, and the segmentation algorithm was tested on 32 postmortem livers in a twofold cross validation manner. The segmentation performance is measured by the Jaccard index (JI) between the segmentation result and the true liver label. RESULTS: The average JI of the segmentation result with the best SSM was 0.8501, which was better compared with the results obtained using conventional SSMs and the results of the previous postmortem liver segmentation with statistically significant difference. CONCLUSIONS: We proposed an algorithm for automated liver segmentation from a PMCT volume, in which an SSM-guided EM algorithm estimated the location and shape parameters of a liver in a given volume accurately. We demonstrated the effectiveness of the proposed algorithm using actual postmortem CT volumes. PMID- 27659285 TI - Room temperature direct band gap emission characteristics of surfactant mediated grown compressively strained Ge films. AB - Compressively strained Ge films have been grown on relaxed Si0.45Ge0.55 virtual substrates using molecular beam epitaxy in the presence of Sb as a surfactant. Structural characterization has shown that films grown in the presence of surfactant exhibit very smooth surfaces with a relatively higher strain value in comparison to those grown without any surfactant. The variation of strain with increasing Ge layer thickness was analyzed using Raman spectroscopy. The strain is found to be reduced with increasing film thickness due to the onset of island nucleation following Stranski-Krastanov growth mechanism. No phonon assisted direct band gap photoluminescence from compressively strained Ge films grown on relaxed Si0.45Ge0.55 has been achieved up to room temperature. Excitation power and temperature dependent photoluminescence have been studied in details to investigate the origin of different emission sub-bands. PMID- 27659286 TI - Nuclear magnetic resonance (NMR) applied to membrane-protein complexes. AB - Increasing evidence suggests that most proteins occur and function in complexes rather than as isolated entities when embedded in cellular membranes. Nuclear magnetic resonance (NMR) provides increasing possibilities to study structure, dynamics and assembly of such systems. In our review, we discuss recent methodological progress to study membrane-protein complexes (MPCs) by NMR, starting with expression, isotope-labeling and reconstitution protocols. We review approaches to deal with spectral complexity and limited spectral spectroscopic sensitivity that are usually encountered in NMR-based studies of MPCs. We highlight NMR applications in various classes of MPCs, including G protein-coupled receptors, ion channels and retinal proteins and extend our discussion to protein-protein complexes that span entire cellular compartments or orchestrate processes such as protein transport across or within membranes. These examples demonstrate the growing potential of NMR-based studies of MPCs to provide critical insight into the energetics of protein-ligand and protein protein interactions that underlie essential biological functions in cellular membranes. PMID- 27659284 TI - High-resolution QTL mapping for grain appearance traits and co-localization of chalkiness-associated differentially expressed candidate genes in rice. AB - BACKGROUND: Grain appearance quality is a main determinant of market value in rice and one of the highly important traits requiring improvement in breeding programs. The genetic basis of grain shape and endosperm chalkiness have been given significant attention because of their importance in affecting grain quality. Meanwhile, the introduction of NGS (Next Generation Sequencing) has a significant part to play in the area of genomics, and offers the possibility for high-resolution genetic map construction, population genetics analysis and systematic expression profile study. RESULTS: A RIL population derived from an inter-subspecific cross between indica rice PYZX and japonica rice P02428 was generated, based on the significant variations for the grain morphology and cytological structure between these two parents. Using the Genotyping-By Sequencing (GBS) approach, 2711 recombination bin markers with an average physical length of 137.68 kb were obtained, and a high-density genetic map was constructed. Global genetic mapping of QTLs affecting grain shape and chalkiness traits was performed across four environments and the newly identified stable loci were obtained. Twelve important QTL clusters were detected, four of which were coincident with the genomic regions of cloned genes or fine mapped QTL reported. Eight novel QTL clusters (including six for grain shape, one for chalkiness, and one for both grain shape and chalkiness) were firstly obtained and highlighted the value and reliability of the QTL analysis. The important QTL cluster on chromosome 5 affects multiple traits including circularity (CS), grain width (GW), area size of grain (AS), percentage of grains with chalkiness (PGWC) and degree of endosperm chalkiness (DEC), indicating some potentially pleiotropic effects. The transcriptome analysis demonstrated an available gene expression profile responsible for the development of chalkiness, and several DEGs (differentially expressed genes) were co-located nearby the three chalkiness related QTL regions on chromosomes 5, 7, and 8. Candidate genes were extrapolated, which were suitable for functional validation and breeding utilization. CONCLUSION: QTLs affecting grain shape (grain width, grain length, length-width ratio, circularity, area size of grain, and perimeter length of grain) and chalkiness traits (percentage of grains with chalkiness and degree of endosperm chalkiness) were mapped with the high-density GBS-SNP based markers. The important differentially expressed genes (DEGs) were co-located in the QTL cluster regions on chromosomes 5, 7 and 8 affecting PGWC and DEC parameters. Our research provides a crucial insight into the genetic architecture of rice grain shape and chalkiness, and acquired potential candidate loci for molecular cloning and grain quality improvement. PMID- 27659287 TI - Emerging role of ivabradine for rate control in atrial fibrillation. AB - Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment. Because If channels were thought to be expressed solely in sinoatrial (SA) nodal tissue, ivabradine was not investigated in heart failure patients with concomitant AF. Subsequent identification of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4), the primary gene responsible for If current expression throughout the myocardium, stimulated interest in the potential role of ivabradine for ventricular rate control in AF. Preclinical studies of ivabradine in animal models with induced AF demonstrated a reduction in HR, with no significant worsening of QT interval or mean arterial pressure. Preliminary human data suggest that ivabradine provides HR reduction without associated hemodynamic complications in patients with AF. Questions remain regarding efficacy, safety, optimal dosing, and length of therapy in these patients. Prospective, randomized studies are needed to determine if ivabradine has a role as a rate-control treatment in patients with AF. PMID- 27659288 TI - The Time Course of Activity within the Dorsal and Rostral-Ventral Anterior Cingulate Cortex in the Emotional Stroop Task. AB - Growing evidence from neuroimaging studies suggest that emotional and cognitive processes are interrelated. Anatomical key structures in this context are the dorsal and rostral-ventral anterior cingulate cortex (dACC and rvACC). However, up to now, the time course of activations within these regions during emotion cognition interactions has not been disentangled. In the present study, we used event-related potentials (ERP) and standardized low-resolution electromagnetic tomography (sLORETA) region of interest (ROI) source localization analyses to explore the time course of neural activations within the dACC and rvACC using a modified emotional Stroop paradigm. ERP components related to Stroop conflict (N200, N450 and late negativity) were analyzed. The time course of brain activations in the dACC and rvACC was strikingly different with more pronounced initial responses in the rvACC followed by increased dACC activity mainly at the late negativity window. Moreover, emotional valence modulated the earlier N450 stage within the rvACC region with higher neural activations in the positive compared to the negative and neutral conditions. Emotional arousal modulated the late negativity stage; firstly in the significant arousal * congruence ERP effect and then the significant higher current density in the low arousal condition within the dACC. Using sLORETA source localization, substantial differences in the activation time courses in the dACC and rvACC could be found during the emotional Stroop task. We suggest that during late negativity, within the dACC, emotional arousal modulated the processing of response conflict, reflected in the correlation between the ex-Gaussian u and the current density in the dACC. PMID- 27659289 TI - Thin-section computed tomography findings of lung adenocarcinoma with inherent metastatic potential. AB - PURPOSE: The solid component of lung ground-glass nodules on thin-section computed tomography (TSCT) reflects cancer cell progression and invasiveness. The purpose of this study was to clarify the cut-off value of preoperative TSCT findings in treating a lesion suspected of being adenocarcinoma and to recognize the timing of surgical resection for lung nodules. METHODS: We reevaluated the TSCT findings in 392 patients with clinical stage IA lung adenocarcinoma who underwent surgical resection between 2003 and 2007. We identified the clinical parameters that were most useful for predicting recurrence and identified a cut off level for each parameter. RESULTS: Recurrence was observed in 75 (19 %) of 392 patients (median follow-up: 7 years). The size of internal consolidation of a lung nodule (SCL) and the ratio of the SCL to the maximum tumor diameter (C/T ratio) were extracted as independent factors that predicted recurrence. Only 1 (0.3 %) patient each with a lung nodule C/T ratio <=0.5 and SCL <=10 mm recurred. These conditions were associated with a significantly better overall survival and recurrence-free survival. CONCLUSION: In patients with clinical stage I lung adenocarcinoma with a C/T ratio <=0.5 and/or SCL <=10 mm on TSCT, surgery is extremely likely to achieve a cure. PMID- 27659291 TI - What am I compressing with my supraglottic device? PMID- 27659290 TI - Clinical significance of mucinous components in rectal cancer after preoperative chemoradiotherapy. AB - PURPOSE: The clinical implications of mucinous components in rectal tumors, especially with regard to the efficacy of neoadjuvant chemoradiotherapy, remain unclear. METHODS: One hundred and thirty rectal cancer patients who received curative resection after neoadjuvant chemoradiotherapy were retrospectively reviewed. Patients were classified into 3 groups according to the proportion of extracellular mucin: low (<5 %), moderate (5-25 %), and high (>25 %). RESULTS: There were 82 (63.1 %), 26 (20.0 %), and 22 (16.9 %) patients in the low, moderate, and high mucin groups, respectively. Patients with a high mucinous tumor component were significantly more likely to have an advanced tumor stage (p = 0.010) and a shorter disease-free (p = 0.002) and distant recurrence-free survivals (p < 0.001), whereas the mucinous tumor component showed no correlation with local recurrence (p = 0.101). A high mucinous component was also an independent predictive factor for a shorter disease-free survival (p = 0.041, hazard ratio = 2.56) and distant recurrence-free survival (p = 0.001, hazard ratio = 5.74) according to a multivariate analysis. CONCLUSIONS: Because the mucinous components showed little correlation with local recurrence, mucinous cancer should not be a determining factor for chemoradiotherapy. However, the frequent occurrence of metachronous distant metastasis among patients with a high mucin component makes this a possible indicator for more robust postoperative adjuvant treatment and close surveillance of recurrence. PMID- 27659292 TI - Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B. AB - BACKGROUND: Factors influencing changes in liver stiffness measurements during long-term nucleoside analogue therapy for chronic hepatitis B (CHB) have not been thoroughly investigated. AIM: To identify determinants of on-treatment fibrosis regression in CHB. METHODS: We performed follow-up liver stiffness and controlled attenuation parameter measurements on nucleoside analogue-treated CHB patients with severe liver fibrosis, according to EASL-ALEH criteria, diagnosed by transient elastography in 2006-2008. Anthropometric measurements and different metabolic parameters were recorded. RESULTS: Among 257 patients with severe liver fibrosis by initial transient elastography, 123 (47.9%) were recruited for reassessment. Median treatment duration was 87.5 (interquartile range 75.3-102.2) months; 97.5% had undetectable HBV DNA. There was a significant reduction in median liver stiffness from 14.6 to 8.3 kPa (P < 0.001). A total of 29.3% had fibrosis regression, with lower rates of 17.9%, 14.9% and 11.5% noted in patients with body-mass index (BMI) >=25 kg/m2 , metabolic syndrome and diabetes, respectively. Absence of BMI >=25 kg/m2 , diabetes and metabolic syndrome, when compared with presence of any one of these three factors, was associated with increased fibrosis regression (43.1% vs. 16.9%, P = 0.001). Multivariate analysis found a lower BMI to be the only factor independently associated with fibrosis regression (P = 0.034, odds ratio 0.68, 95% CI 0.48-0.97). No association was noted between controlled attenuation parameter measurements and fibrosis regression (P > 0.05). CONCLUSION: An increased BMI hindered fibrosis regression in patients with chronic hepatitis B during nucleoside analogue treatment, suggesting that control of metabolic risk factors, in addition to virologic suppression via antiviral therapy, might be needed to halt the fibrogenic process in chronic hepatitis B. PMID- 27659293 TI - The promise of cyborg intelligence. AB - Yu et al. (2016) demonstrated that algorithms designed to find efficient routes in standard mazes can be integrated with the natural processes controlling rat navigation and spatial choices, and they pointed out the promise of such "cyborg intelligence" for biorobotic applications. Here, we briefly describe Yu et al.'s work, explore its relevance to the study of comparative cognition, and indicate how work involving cyborg intelligence would benefit from interdisciplinary collaboration between behavioral scientists and engineers. PMID- 27659295 TI - Iranian kidney market in limbo: a commentary on "The ambiguous lessons of the Iranian model of paid living kidney donation". AB - Sigrid Fry-Revere's The Kidney Sellers: A Journey of Discovery in Iran, an allegedly first-hand examination of the Iranian paid kidney donation model, has been criticized by Koplin in an essay formerly published in the Monash Bioethics Review. Koplin especially challenges Fry-Revere's claim that financially compensating kidney vendors might facilitate altruistic kidney donation. The current situation in Iran, according to Koplin, suggests that the market model has undermined altruistic donation. On this point, this commentary tries to show that healthcare policymakers in Iran no longer see the Iranian paid kidney donation model as a sustainable and ethically justifiable status quo. Briefly touching on the criticisms that have been made even by some positive commentators of the Iranian model, this commentary aims to call attention to the fact that the current dynamic within healthcare policymaking in Iran seeks primarily to decrease its reliance on the organ market instead of revising and modifying it. This complicates the plausibility of any kind of extrapolation, replication or extracting empirical support from the Iranian model to create organ markets in other countries, for example, as Fry-Revere suggests to conduct a trial of a financially incentivized kidney donation scheme in the US. The conclusion is that the Iranian healthcare system should tackle the organ shortage through increasing altruistic living and postmortem kidney donations. This might also provide, finally, a space for conducting extensive and long-term follow-up studies on well being, satisfaction and social integration of Iranian kidney vendors. PMID- 27659294 TI - Final overall survival in JO22903, a phase II, open-label study of first-line erlotinib for Japanese patients with EGFR mutation-positive non-small-cell lung cancer. AB - BACKGROUND: In Japan, the clinical efficacy of erlotinib monotherapy in epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer was demonstrated in the phase II JO22903 trial, which reported a median progression free survival of 11.8 months. Here we report final overall survival data from JO22903. METHODS: JO22903 (JapicCTI-101085) was a single-arm, multicenter, phase II, open-label, non-randomized study of first-line erlotinib monotherapy in EGFR mutation-positive non-small-cell lung cancer. Eligible patients (>=20 years) with stage IIIB/IV or recurrent non-small-cell lung cancer and confirmed activating mutations of EGFR (exon 19 deletion or L858R point mutation in exon 21) received oral erlotinib 150 mg/day until disease progression or unacceptable toxicity. The primary endpoints were progression-free survival and safety; overall survival was a secondary endpoint. RESULTS: At the final analysis, 102 patients were included in the modified intent-to-treat population and 103 in the safety population. Median follow-up was 32.3 months. Median overall survival was 36.3 months (95 % confidence interval 29.4-not reached). Subgroup analyses of overall survival suggested that the presence of brain metastases was a negative prognostic factor (median overall survival 22.7 months, 95 % confidence interval 19.6-29.4). The impact on overall survival of using versus not using EGFR tyrosine kinase inhibitors in any line of treatment following disease progression was unclear (median 32.8 versus 36.3 months, respectively). No new safety issues were observed. CONCLUSION: In this survival update, single-agent erlotinib achieved a median overall survival of more than 3 years in patients with EGFR mutation positive non-small-cell lung cancer. PMID- 27659296 TI - Randomized clinical study assessing two membranes for guided bone regeneration of peri-implant bone defects: clinical and histological outcomes at 6 months. AB - PURPOSE: To test whether or not one of two membranes is superior for peri-implant guided bone regeneration in terms of clinical and histologic outcomes. MATERIAL AND METHODS: In 27 patients, 27 two-piece dental implants were placed in single tooth gaps in the esthetic area. Buccal dehiscence and/or fenestration-type defects were regenerated using demineralized bovine bone mineral and randomly covered with either a resorbable membrane (RES) or a titanium-reinforced non resorbable membrane (N-RES). Clinical measurements included vertical defect resolution and the horizontal thickness of regenerated bone at implant placement and at 6 months. Statistics were performed by means of nonparametric testing. RESULTS: The remaining mean vertical defect measured 4 mm (+/-2.07) (RES) and 2.36 mm (+/-2.09) (N-RES) (P = 0.044) at baseline and 0.77 mm (+/-0.85) (RES) and 0.21 mm (+/-0.80) (N-RES) (P = 0.021) at re-entry. This translated into a defect resolution of 85% (RES) and 90.7% (N-RES) (P = 0.10). The horizontal thickness after augmentation measured 3.46 mm (+/-0.52) (RES) and 2.82 mm (+/-0.50) (N-RES) (P = 0.004). The mean loss in horizontal thickness from baseline to re-entry measured 2.23 mm (SD +/-1.21) (RES) and 0.14 mm (+/-0.79) (N-RES) (P = 0.017). The horizontal changes in thickness at the implant shoulder level were statistically significant between the groups (P = 0.0001). CONCLUSIONS: Both treatment modalities were clinically effective in regenerating bone as demonstrated by a similar horizontal thickness and vertical defect fill at 6 months. The N-RES group exhibited significantly less horizontal bone thickness reduction from baseline to follow-up. PMID- 27659297 TI - Medical Home Characteristics and Quality of Diabetes Care in Safety Net Clinics. AB - We examined associations between patient-centered medical home (PCMH) characteristics and quality of diabetes care in 15 safety net clinics in five states. Surveys among clinic directors assessed PCMH characteristics using the Safety Net Medical Home Scale. Chart audits among 864 patients assessed diabetes process and outcome measures. We modeled the odds of the patient receiving performance measures as a function of total PCMH score and of PCMH subscales and covariates. PCMH characteristics had mixed, inconsistent associations with the quality of diabetes care. The PCMH model may require refinement in design and implementation to improve diabetes care among vulnerable populations. PMID- 27659298 TI - Origin of multi-level switching and telegraphic noise in organic nanocomposite memory devices. AB - The origin of negative differential resistance (NDR) and its derivative intermediate resistive states (IRSs) of nanocomposite memory systems have not been clearly analyzed for the past decade. To address this issue, we investigate the current fluctuations of organic nanocomposite memory devices with NDR and the IRSs under various temperature conditions. The 1/f noise scaling behaviors at various temperature conditions in the IRSs and telegraphic noise in NDR indicate the localized current pathways in the organic nanocomposite layers for each IRS. The clearly observed telegraphic noise with a long characteristic time in NDR at low temperature indicates that the localized current pathways for the IRSs are attributed to trapping/de-trapping at the deep trap levels in NDR. This study will be useful for the development and tuning of multi-bit storable organic nanocomposite memory device systems. PMID- 27659299 TI - Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder. AB - Deficits in attention have been implicated in Obsessive-Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs-fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN-SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN-SN networks that subserve attentional processes and this effect of OCD on DMN-SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN-SN connectivity may represent a trans-diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN-SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp 38:678 687, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27659302 TI - A bead-based western for high-throughput cellular signal transduction analyses. AB - Dissecting cellular signalling requires the analysis of large number of proteins. The DigiWest approach we describe here transfers the western blot to a bead-based microarray platform. By combining gel-based protein separation with immobilization on microspheres, hundreds of replicas of the initial blot are created, thus enabling the comprehensive analysis of limited material, such as cells collected by laser capture microdissection, and extending traditional western blotting to reach proteomic scales. The combination of molecular weight resolution, sensitivity and signal linearity on an automated platform enables the rapid quantification of hundreds of specific proteins and protein modifications in complex samples. This high-throughput western blot approach allowed us to identify and characterize alterations in cellular signal transduction that occur during the development of resistance to the kinase inhibitor Lapatinib, revealing major changes in the activation state of Ephrin-mediated signalling and a central role for p53-controlled processes. PMID- 27659300 TI - Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man. AB - The current test systems employed by pharmaceutical industry are poorly predictive for drug-induced liver injury (DILI). The 'MIP-DILI' project addresses this situation by the development of innovative preclinical test systems which are both mechanism-based and of physiological, pharmacological and pathological relevance to DILI in humans. An iterative, tiered approach with respect to test compounds, test systems, bioanalysis and systems analysis is adopted to evaluate existing models and develop new models that can provide validated test systems with respect to the prediction of specific forms of DILI and further elucidation of mechanisms. An essential component of this effort is the choice of compound training set that will be used to inform refinement and/or development of new model systems that allow prediction based on knowledge of mechanisms, in a tiered fashion. In this review, we focus on the selection of MIP-DILI training compounds for mechanism-based evaluation of non-clinical prediction of DILI. The selected compounds address both hepatocellular and cholestatic DILI patterns in man, covering a broad range of pharmacologies and chemistries, and taking into account available data on potential DILI mechanisms (e.g. mitochondrial injury, reactive metabolites, biliary transport inhibition, and immune responses). Known mechanisms by which these compounds are believed to cause liver injury have been described, where many if not all drugs in this review appear to exhibit multiple toxicological mechanisms. Thus, the training compounds selection offered a valuable tool to profile DILI mechanisms and to interrogate existing and novel in vitro systems for the prediction of human DILI. PMID- 27659303 TI - Global properties of vector-host disease models with time delays. AB - Since there exist extrinsic and intrinsic incubation periods of pathogens in the feedback interactions between the vectors and hosts, it is necessary to consider the incubation delays in vector-host disease transmission dynamics. In this paper, we propose vector-host disease models with two time delays, one describing the incubation period in the vector population and another representing the incubation period in the host population. Both distributed and discrete delays are used. By constructing suitable Liapunov functions, we obtain sufficient conditions for the global stability of the endemic equilibria of these models. The analytic results reveal that the global dynamics of such vector-host disease models with time delays are completely determined by the basic reproduction number. Some specific cases with discrete delay are studied and the corresponding results are improved. PMID- 27659305 TI - A Single Talent Immunogenic Membrane Antigen and Novel Prognostic Predictor: voltage-dependent anion channel 1 (VDAC1) in Pancreatic Cancer. AB - Immunogenic membrane antigens associated with multiple biological functions of human cancer cells, have significant value in molecule diagnosis and targeted therapy. Here we screened immunogenic membrane antigens in pancreatic cancer by immunobloting IgG purified from sera of 66 pancreatic cancer patients with membrane proteins separated from two-dimensional PAGE of human pancreatic cancer cell line SWl990, and identified voltage-dependent anion channel 1 (VDAC1) as one of the potential immunogenic membrane antigens. Further studies focusing on VDAC1 demonstrated that VDAC1 mRNA and protein were significantly expressed in the tested pancreatic cancer cell lines. VDAC1 silencing with RNAi significantly decreased cell growth, invasion and migration in the pancreatic cancer cell line Capan-1. Additionally, VDAC1 expression was upregulated in pancreatic cancer tissue compared with normal pancreas samples and patients with low VDAC1 expression had a significantly greater median survival compared to those with high expression (27.0 months vs. 17.8 months, P = 0.039). In multivariable analysis, VDAC1 staining was an independent prognostic factor for survival [(Hazard-Ratio) HR = 1.544, 95% CI = 0.794-3.0, P = 0.021]. These results demonstrated that VDAC1 may be a candidate immunogenic membrane antigen for pancreatic cancer, a potential independent prognostic marker, and an ideal drug target. PMID- 27659304 TI - An impulsive modelling framework of fire occurrence in a size-structured model of tree-grass interactions for savanna ecosystems. AB - Fires and mean annual rainfall are major factors that regulate woody and grassy biomasses in savanna ecosystems. Within the savanna biome, conditions of long lasting coexistence of trees and grasses have been often studied using continuous time modelling of tree-grass competition. In these studies, fire is a time continuous forcing while the relationship between woody plant size and fire sensitivity is not systematically considered. In this paper, we propose a new mathematical framework to model tree-grass interactions that takes into account both the impulsive nature of fire occurrence and size-dependent fire sensitivity (via two classes of woody plants). We carry out a qualitative analysis that highlights ecological thresholds and bifurcation parameters that shape the dynamics of the savanna-like systems within the main ecological zones. Through a qualitative analysis, we show that the impulsive modelling of fire occurrences leads to more diverse behaviors including cases of grassland, savanna and forest tristability and a more realistic array of solutions than the analogous time continuous fire models. Numerical simulations are carried out with respect to the three main ecological contexts (moist, mesic, semi-arid) to illustrate the theoretical results and to support a discussion about the bifurcation parameters and the advantages of the model. PMID- 27659306 TI - Efficacy of extracorporeal cardiopulmonary resuscitation compared to conventional cardiopulmonary resuscitation for adult cardiac arrest patients: a systematic review and meta-analysis. AB - We performed a meta-analysis to compare the impact of extracorporeal cardiopulmonary resuscitation (ECPR) to that of conventional cardiopulmonary resuscitation (CCPR) in adult patients who experience cardiac arrest of cardiac origin. A literature search was performed using criteria set forth in a predefined protocol. Report inclusion criteria were that ECPR was compared to CCPR in adult patients with cardiac arrest of cardiac origin, and that survival and neurological outcome data were available. Exclusion criteria were reports describing non-cardiac origin arrest, review articles, editorials, and nonhuman studies. The efficacies of ECPR and CCPR were compared in terms of survival and neurological outcome. A total of 38,160 patients from 7 studies were ultimately included. ECPR showed similar survival (odds ratio [OR] 2.26, 95% confidence interval [CI] 0.45-11.20) and neurologic outcomes (OR 3.14, 95% CI 0.66-14.85) to CCPR in out-of-hospital cardiac arrest patients. For in-hospital cardiac arrest (IHCA) patients, however, ECPR was associated with significantly better survival (OR 2.40, 95% CI 1.44-3.98) and neurologic outcomes (OR 2.63, 95% CI 1.38-5.02) than CCPR. Hence, ECPR may be more effective than CCPR as an adjuvant therapy for survival and neurologic outcome in cardiac-origin IHCA patients. PMID- 27659301 TI - Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery. AB - : Ageing, an unanswered question in the medical field, is a multifactorial process that results in a progressive functional decline in cells, tissues and organisms. Although it is impossible to prevent ageing, slowing down the rate of ageing is entirely possible to achieve. Traditional Chinese medicine (TCM) is characterized by the nourishing of life and its role in anti-ageing is getting more and more attention. This article summarizes the work done on the natural products from TCM that are reported to have anti-ageing effects, in the past two decades. The effective anti-ageing ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, alkaloids and others. Astragaloside, Cistanche tubulosa acteoside, icariin, tetrahydrocurcumin, quercetin, butein, berberine, catechin, curcumin, epigallocatechin gallate, gastrodin, 6-Gingerol, glaucarubinone, ginsenoside Rg1, luteolin, icarisid II, naringenin, resveratrol, theaflavin, carnosic acid, catalpol, chrysophanol, cycloastragenol, emodin, galangin, echinacoside, ferulic acid, huperzine, honokiol, isoliensinine, phycocyanin, proanthocyanidins, rosmarinic acid, oxymatrine, piceid, puerarin and salvianolic acid B are specified in this review. Simultaneously, chemical structures of the monomers with anti-ageing activities are listed, and their source, model, efficacy and mechanism are also described. The TCMs with anti-ageing function are classified according to their action pathways, including the telomere and telomerase, the sirtuins, the mammalian target of rapamycin, AMP-activated kinase and insulin/insulin-like growth factor 1 signalling pathway, free radicals scavenging and the resistance to DNA damage. Finally, Chinese compound prescription and extracts related to anti-ageing are introduced, which provides the basis and the direction for the further development of novel and potential drugs. LINKED ARTICLES: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. PMID- 27659307 TI - Rim15 and Sch9 kinases are involved in induction of autophagic degradation of ribosomes in budding yeast. AB - Autophagic degradation of ribosomes is promoted by nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1). Here we show that selective autophagic degradation of ribosomes (called ribophagy) after TORC1 inactivation requires the specific autophagy receptor Atg11. Rim15 protein kinase upregulated ribophagy, while it downregulated non-selective degradation of ribosomes. PMID- 27659308 TI - [Percutaneous internal fixation of pelvic fractures. German version]. AB - BACKGROUND: Percutaneous internal fixation of pelvic fractures is increasing in popularity with multiple new techniques reported. OBJECTIVES: The purpose of this article is to outline the imaging, indication, planning, equipment, surgical technique and complications of these methods. METHODS: A review of the literature is provided and the techniques for anterior and posterior pelvic stabilization are discussed. RESULTS: High-quality preoperative CT scans are essential in planning for this technique. The anterior internal fixator ("InFix") is an effective method for stabilizing the anterior ring and should be usually used in conjunction with posterior fixation. Good technique avoids neurovascular injury, which can be a devastating complication. The retrograde anterior column screw (RACS) is a technique that can be used in most patients, although in smaller patients smaller screw diameters may be needed. The entry point for the screw is more lateral in women than men. Iliosacral screws (ISS) are an effective method of posterior stabilization and can be placed using 2D or 3D fluoroscopy, computer navigation or CT navigation. CONCLUSION: Percutaneous fixation of pelvic fractures requires high-quality imaging and can be aided by computer navigation. Safe techniques are reproducible; however, not all patients and fracture patterns can be treated using these techniques. PMID- 27659309 TI - Percutaneous internal fixation of pelvic fractures. AB - BACKGROUND: Percutaneous internal fixation of pelvic fractures is increasing in popularity with multiple new techniques reported. OBJECTIVES: The purpose of this article is to outline the imaging, indication, planning, equipment, surgical technique and complications of these methods. METHODS: A review of the literature is provided and the techniques for anterior and posterior pelvic stabilisation are discussed. RESULTS: High-quality preoperative CT scans are essential in planning for this technique. The anterior internal fixator ("InFix") is an effective method for stabilising the anterior ring and should be usually used in conjunction with posterior fixation. Good technique avoids neurovascular injury, which can be a devastating complication. The retrograde anterior column screw (RACS) is a technique that can be used in most patients, although in smaller patients smaller screw diameters may be needed. The entry point for the screw is more lateral in women than men. Iliosacral screws (ISS) are an effective method of posterior stabilisation and can be placed using 2D or 3D fluoroscopy, computer navigation or CT navigation. CONCLUSION: Percutaneous fixation of pelvic fractures requires high-quality imaging and can be aided by computer navigation. Safe techniques are reproducible; however, not all patients and fracture patterns can be treated using these techniques. PMID- 27659311 TI - The discovery of the hydrogen bond from p-Nitrothiophenol by Raman spectroscopy: Guideline for the thioalcohol molecule recognition tool. AB - Inter- and intra- molecular hydrogen bonding plays important role in determining molecular structure, physical and chemical properties, which may be easily ignored for molecules with a non-typical hydrogen bonding structure. We demonstrated in this paper that the hydrogen bonding is responsible for the different Raman spectra in solid and solution states of p-Nitrothiophenol (PNTP). The consistence of the theoretical calculation and experiment reveals that the intermolecular hydrogen bonding yields an octatomic ring structure (8) of PNTP in the solid state, confirmed by the characteristic S-H---O stretching vibration mode at 2550 cm-1; when it comes to the solution state, the breakage of hydrogen bond of S-H---O induced the S-H stretching vibration at 2590 cm-1. Our findings may provide a simple and fast method for identifying the intermolecular hydrogen bonding. PMID- 27659310 TI - Human cathelicidin LL-37 enhance the antibiofilm effect of EGCG on Streptococcus mutans. AB - BACKGROUND: Streptococcus mutans forms biofilms as a resistance mechanism against antimicrobial agents in the human oral cavity. We recently showed that human cathelicidin LL-37 exhibits inhibitory effects on biofilm formation of S. mutans through interaction with lipoteichoic acid (LTA), but without antibacterial or biofilm dispersal abilities. (-)-Epigallocatechin gallate (EGCG) is the most abundant constituent of tea catechins that has the greatest anti-infective potential to inhibit the growth of various microorganisms and biofilm formation. Therefore, in this study, we evaluated whether LL-37 interacts with EGCG to enhance the antibiofilm effect of EGCG on S. mutans biofilm formation. METHODS: Clinical S. mutans strains (n = 10) isolated from children's saliva were tested in a biofilm formation assay. The antibiofilm effect of EGCG with and without LL 37 was analyzed by the minimum biofilm eradication concentration assay and confirmed using field emission-scanning electron microscopy. In addition, the interaction among EGCG, LL-37, and LTA of S. mutans was determined using quartz crystal microbalance analysis. RESULTS: EGCG killed 100 % of planktonic S. mutans within 5 h, inhibited biofilm formation within 24 h, and reduced bacteria cells in preformed biofilms within 3 h at a concentration of 0.2 mg/mL. However, EGCG did not appear to interact with LTA. LL-37 effectively enhanced the bactericidal activity of EGCG against biofilm formation and preformed biofilms as determined by quantitative crystal violet staining and field emission-scanning electron microscopy. In addition, quartz crystal microbalance analysis revealed that LL-37 interacted with EGCG and promoted binding between EGCG and LTA of S. mutans. CONCLUSIONS: We show that LL-37 enhances the antibiofilm effect of EGCG on S. mutans. This finding provides new knowledge for dental treatment by using LL-37 as a potential antibiofilm compound. PMID- 27659314 TI - GP who supplied abortion drug in "fake sheikh" sting is struck off. PMID- 27659312 TI - A 16-bit Coherent Ising Machine for One-Dimensional Ring and Cubic Graph Problems. AB - Many tasks in our modern life, such as planning an efficient travel, image processing and optimizing integrated circuit design, are modeled as complex combinatorial optimization problems with binary variables. Such problems can be mapped to finding a ground state of the Ising Hamiltonian, thus various physical systems have been studied to emulate and solve this Ising problem. Recently, networks of mutually injected optical oscillators, called coherent Ising machines, have been developed as promising solvers for the problem, benefiting from programmability, scalability and room temperature operation. Here, we report a 16-bit coherent Ising machine based on a network of time-division-multiplexed femtosecond degenerate optical parametric oscillators. The system experimentally gives more than 99.6% of success rates for one-dimensional Ising ring and nondeterministic polynomial-time (NP) hard instances. The experimental and numerical results indicate that gradual pumping of the network combined with multiple spectral and temporal modes of the femtosecond pulses can improve the computational performance of the Ising machine, offering a new path for tackling larger and more complex instances. PMID- 27659313 TI - High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice. AB - Type 2 Diabetes (T2D), a major public health issue reaching worldwide epidemic, has been correlated with lower olfactory abilities in humans. As olfaction represents a major component of feeding behavior, its alteration may have drastic consequences on feeding behaviors that may in turn aggravates T2D. In order to decipher the impact of T2D on the olfactory epithelium, we fed mice with a high fructose diet (HFruD) inducing early diabetic state in 4 to 8 weeks. After only 4 weeks of this diet, mice exhibited a dramatic decrease in olfactory behavioral capacities. Consistently, this decline in olfactory behavior was correlated to decreased electrophysiological responses of olfactory neurons recorded as a population and individually. Our results demonstrate that, in rodents, olfaction is modified by HFruD-induced diabetes. Functional, anatomical and behavioral changes occurred in the olfactory system at a very early stage of the disease. PMID- 27659315 TI - Prevalence of Fusobacterium necrophorum in tonsils from patients with chronic tonsillitis. AB - CONCLUSION: There was a high prevalence of Fusobacterium necrophorum (FN) in patients with chronic tonsillitis in the age group 15-23 years. This indicates that FN might play an important role in the pathogenesis of chronic tonsillitis in this age group, which is also the age group in which chronic or recurrent tonsillitis is most common. OBJECTIVES: The role of FN in patients with acute and chronic tonsillitis is unclear. Thus, this study investigated the occurrence of FN in tonsils of patients with chronic tonsillitis. The aim of the study was to determine the prevalence of FN in patients that underwent tonsillectomy due to chronic tonsillitis. This study also investigated if FN was found at different areas in the tonsils. METHOD: One hundred and twenty-six consecutive patients undergoing tonsillectomy due to chronic tonsillitis were included from the ENT clinics at Sunderby Hospital and Gallivare Hospital, Sweden. Both children and adults were included to encompass various age groups (age =2-57 years). Culture swabs were taken from three different levels of the tonsils - the surface, the crypts, and the inner core of the tonsils. Selective agar plates for detecting FN were used for culture. Culture was also made for detecting beta-hemolytic streptococci, Haemophilus influenzae, and Arcanobacterium. RESULTS: FN was the most common pathogen (19%). The highest prevalence of FN was found in the age group 15-23 years (in 34% of the patients). FN was detected both at the surface and in the core of the tonsils. Furthermore, in the few patients where FN was not detected in all three areas, FN was always detected at the tonsillar surface, in spite of being an anaerobic bacterium. Streptococci group G and C also occurred most frequently (30%) in the same age group as FN (15-23 years), whereas Streptococci group A was more evenly spread among the age groups. PMID- 27659316 TI - Association of vitamin D deficiency with hepatitis B virus - related liver diseases. AB - BACKGROUND: As an immune modulator, vitamin D is involved in various pathophysiological mechanisms in a plethora of diseases. This study aims to correlate the vitamin D deficiency status and clinical progression of liver diseases associated with hepatitis B virus (HBV) infection in patients in Vietnam and to compare it to healthy controls. METHODS: We quantified the levels of total vitamin D [25-(OH) D2 and D3] in serum samples from 400 HBV patients (chronic hepatitis B infection [CHB], n = 165; HBV-associated liver cirrhosis [LC], n = 127; HBV-associated hepatocellular carcinoma [HCC], n = 108) and 122 unrelated healthy controls (HC). Univariate and multivariate analyses were performed in order to determine the association between vitamin D levels and distinct clinical parameters. RESULTS: The prevalence of vitamin D inadequacy (<30 ng/mL) was high among healthy individuals (81.7 %) as well as in HBV patients (84.3 %). Vitamin D deficiency (<20 ng/ml) or severe deficiency (<10 ng/ml) was observed more frequently among HBV patients (52 %) and subgroups (CHB, 47.8 %; LC, 54.4 %; HCC, 55.3 %) compared to the control group (32.5 %) (P < 0.001). Vitamin D levels and HBV-DNA load were strongly and inversely correlated (rho = -0.57, P < 0.0001). Multivariate regression analysis also revealed an independent association of HBV DNA loads with low vitamin D levels (P = 0.0004). In addition, reduced vitamin D levels were associated with significant clinical progression of LC (Child-Pugh C versus Child-Pugh A, P = 0.0018; Child-Pugh C versus Child-Pugh B, P = 0.016). CONCLUSIONS: Vitamin D deficiency was observed in the majority of HBV-infected patients and associated with adverse clinical outcomes. Our findings suggest that substitution of vitamin D may be a supportive option in the treatment of chronic liver diseases, in particular of HBV-associated disorders. PMID- 27659317 TI - Acute and chronic infections with nonprimate hepacivirus in young horses. AB - The recently discovered nonprimate hepacivirus (NPHV) naturally infects horses and is the closest known homolog of hepatitis C virus to date. Within a follow-up study acute field infections were monitored in four young Thoroughbred horses until the ages of 12-13 months. Serum samples were analyzed for the presence of NPHV RNA and anti-NPHV NS3 antibodies and liver specific parameters were evaluated. The four young horses were not able to clear infection, but remained chronically infected for the entire monitored time period despite the presence of NPHV specific antibodies. PMID- 27659318 TI - Autism genes: the continuum that connects us all. PMID- 27659319 TI - Identification of novel SNP in caprine beta-lactoglobulin gene. AB - beta-lactoglobulin (beta-LG) gene is suggested as a functional candidate gene for milk yield and milk composition. beta-LG polymorphism has been reported to be associated with milk yield in cows, sheep and Indian goats. This study was performed to identify SNPs in exon 7 of beta-LG gene and their association with milk traits in Iranian local Mahabadi goats using polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and PCR-sequencing. Three SSCP patterns were observed with frequencies 0.678, 0.096 and 0.226, respectively. Subsequently, after sequencing each unique pattern nine novel mutations were identified. These mutations include: T InDel at nucleotide position 93 and substitutions T/C, T/G, T/C, G/T, T/G,T/C, G/A and A/T at nucleotide positions 99, 124, 126, 134, 147, 156, 176 and 177, respectively. Of these, seven mutations were same among the genotypic patterns while differences were related to T deletion and insertion (-/T) at nucleotide position 93 with frequencies 0.22 and 0.78 in the presence and absence of T allele, respectively; and substitution (A/T) at nucleotide position 177 with frequencies 0.16 and 0.84 for A and T alleles, respectively. Milk traits including milk production (gr), milk fat and protein (%) were also measured. These findings demonstrated that beta-LG gene had a significant effect on milk protein percentage (P < 0.05), but had no significant effect on milk production and milk fat percentage. PMID- 27659320 TI - Evolution of increased larval competitive ability in Drosophila melanogaster without increased larval feeding rate. AB - Multiple experimental evolution studies on Drosophila melanogaster in the 1980s and 1990s indicated that enhanced competitive ability evolved primarily through increased larval tolerance to nitrogenous wastes and increased larval feeding and foraging rate, at the cost of efficiency of food conversion to biomass, and this became the widely accepted view of how adaptation to larval crowding evolves in fruitflies.We recently showed that populations of D. ananassae and D. n. nasuta subjected to extreme larval crowding evolved greater competitive ability without evolving higher feeding rates, primarily through a combination of reduced larval duration, faster attainment of minimum critical size for pupation, greater efficiency of food conversion to biomass, increased pupation height and, perhaps, greater urea/ammonia tolerance. This was a very different suite of traits than that seen to evolve under similar selection in D. melanogaster and was closer to the expectations from the theory of K-selection. At that time, we suggested two possible reasons for the differences in the phenotypic correlates of greater competitive ability seen in the studies with D. melanogaster and the other two species. First, that D. ananassae and D. n. nasuta had a very different genetic architecture of traits affecting competitive ability compared to the long-term laboratory populations of D. melanogaster used in the earlier studies, either because the populations of the former two species were relatively recently wild caught, or by virtue of being different species. Second, that the different evolutionary trajectories in D. ananassae and D. n. nasuta versus D. melanogaster were a reflection of differences in the manner in which larval crowding was imposed in the two sets of selection experiments. The D. melanogaster studies used a higher absolute density of eggs per unit volume of food, and a substantially larger total volume of food, than the studies on D. ananassae and D. n. nasuta. Here, we show that long-term laboratory populations of D. melanogaster, descended from some of the populations used in the earlier studies, evolve essentially the same set of traits as the D. ananassae and D. n. nasuta crowding-adapted populations when subjected to a similar larval density at low absolute volumes of food. As in the case of D. ananassae and D. n. nasuta, and in stark contrast to earlier studies with D. melanogaster, these crowding-adapted populations of D. melanogaster did not evolve greater larval feeding rates as a correlate of increased competitive ability. The present results clearly suggest that the suite of phenotypes through which the evolution of greater competitive ability is achieved in fruitflies depends critically not just on larval density per unit volume of food, but also on the total amount of food available in the culture vials. We discuss these results in the context of an hypothesis about how larval density and the height of the food column in culture vials might interact to alter the fitness costs and benefits of increased larval feeding rates, thus resulting in different routes to the evolution of greater competitive ability, depending on the details of exactly how the larval crowding was implemented. PMID- 27659321 TI - Maternal MTHFR polymorphism (677 C-T) and risk of Down's syndrome child: meta analysis. AB - Methylenetetrahydrofolate reductase (MTHFR) is the most important gene that participates in folate metabolism. Presence of valine instead of alanine at position 677 and elevated levels of homocystein causes DNA hypomethylation which in turn favours nondisjunction. In this study, we conducted a meta-analysis to establish link between maternal single-nucleotide polymorphism (SNP) and birth of Down's syndrome (DS) child. A total of 37 case-control studies were selected for analysis including our own, in which we investigated 110 cases and 111 control mothers. Overall, the result of meta-analysis showed significant risk of DS affected by the presence of maternal SNP (MTHFR 677 C-T OR = 0.816, 95% CI = 0.741-0.900, P <0.0001). Heterogeneity of high magnitude was observed among the studies. The chi-square value suggested a highly significant association between homozygous mutant TT genotype and birth of DS child (chi2 = 23.63, P = 0.000). Genetic models suggested that 'T' allele possesses high risk for DS whether present in dominant (OR = 1.23, 95% CI = 1.13-1.34); codominant (OR = 1.17, 95% CI = 1.10-1.25) or recessive (OR = 1.21, 95% CI = 1.05-1.38) form. The analysis from all 37 studies combined together suggested that MTHFR 677 C-T is a major risk factor for DS birth. PMID- 27659322 TI - Genomewide analysis of the lateral organ boundaries domain gene family in Vitis vinifera. AB - In plants, the transcription factor families have been implicated in many important biological processes. These processes include morphogenesis, signal transduction and environmental stress responses. Proteins containing the lateral organ boundaries domain (LBD), which encodes a zinc finger-like domain are only found in plants. This finding indicates that this unique gene family regulates only plant-specific biological processes. LBD genes play crucial roles in the growth and development of plants such as Arabidopsis, Oryza sativa, Zea mays, poplar, apple and tomato. However, relatively little is known about the LBD genes in grape (Vitis vinifera). In this study, we identified 40 LBD genes in the grape genome. A complete overview of the chromosomal locations, phylogenetic relationships, structures and expression profiles of this gene family during development in grape is presented here. Phylogenetic analysis showed that the LBD genes could be divided into classes I and II, together with LBDs from Arabidopsis. We mapped the 40 LBD genes on the grape chromosomes (chr1-chr19) and found that 37 of the predicted grape LBD genes were distributed in different densities across 12 chromosomes. Grape LBDs were found to share a similar intron/exon structure and gene length within the same class. The expression profiles of grape LBD genes at different developmental stages were analysed using microarray data. Results showed that 21 grape LBD genes may be involved in grape developmental processes, including preveraison, veraison and ripening. Finally, we analysed the expression patterns of six LBD genes through quantitative real time polymerase chain reation analysis. The six LBD genes showed differential expression patterns among the three representative grape tissues, and five of these genes were found to be involved in responses to mannitol, sodium chloride, heat stress and low temperature treatments. To our knowledge, this is the first study to analyse the LBD gene family in grape and provides valuable information for classification and functional investigation of this gene family. PMID- 27659323 TI - A deep sequencing analysis of transcriptomes and the development of EST-SSR markers in mungbean (Vigna radiata). AB - Mungbean (Vigna radiata L. Wilczek) is one of the most important leguminous food crops in Asia. We employed Illumina paired-end sequencing to analyse transcriptomes of three different mungbean genotypes. A total of 38.3-39.8 million pairedend reads with 73 bp lengths were generated. The pooled reads from the three libraries were assembled into 56,471 transcripts. Following a cluster analysis, 43,293 unigenes were obtained with an average length of 739 bp and N50 length of 1176 bp. Of the unigenes, 34,903 (80.6%) had significant similarity to known proteins in the NCBI nonredundant protein database (Nr), while 21,450 (58.4%) had BLAST hits in the Swiss-Prot database (E-value<10-5). Further, 1245 differential expression genes were detected among three mungbean genotypes. In addition, we identified 3788 expressed sequence tag-simple sequence repeat (EST SSR) motifs that could be used as potential molecular markers. Among 320 tested loci, 310 (96.5%) yielded amplification products, and 151 (47.0%) exhibited polymorphisms among six mungbean accessions. These transcriptome data and mungbean EST-SSRs could serve as a valuable resource for novel gene discovery and the marker-assisted selective breeding of this species. PMID- 27659324 TI - Comparative analysis of codon usage bias in Crenarchaea and Euryarchaea genome reveals differential preference of synonymous codons to encode highly expressed ribosomal and RNA polymerase proteins. AB - The present study was undertaken to investigate the pattern of optimal codon usage in Archaea. Comparative analysis was executed to understand the pattern of codon usage bias between the high expression genes (HEG) and the whole genomes in two Archaeal phyla, Crenarchaea and Euryarchaea. The G+C% of the HEG was found to be less in comparison to the genome G+C% in Crenarchaea, whereas reverse was the case in Euryarchaea. The preponderance of U/A ending codons that code for HEG in Crenarchaea was in sharp contrast to the C/G ended ones in Euryarchaea. The analysis revealed prevalence of Uending codons even within theWWY(nucleotide ambiguity code) families in Crenarchaea vis-a-vis Euryarchaea, bacteria and Eukarya. No plausible interpretation of the observed disparity could be made either in the context of tRNA gene composition or genome G+C%. The results in this study attested that the preferential biasness for codons in HEG of Crenarchaea might be different from Euryarchaea. The main highlights are (i) varied CUB in the HEG and in the whole genomes in Euryarchaea and Crenarchaea. (ii) Crenarchaea was found to have some unusual optimal codons (OCs) compared to other organisms. (iii) G+C% (and GC3) of the HEG were different from the genome G+C% in the two phyla. (iv) Genome G+C% and tRNA gene number failed to explain CUB in Crenarchaea. (v) Translational selection is possibly responsible for A+T rich OCs in Crenarchaea. PMID- 27659325 TI - Frequent alterations of SLIT2-ROBO1-CDC42 signalling pathway in breast cancer: clinicopathological correlation. AB - The aim of the study was to understand the role of SLIT2-ROBO1/2-CDC42 signalling pathways in development of breast cancer (BC). Primary BC samples (n = 150), comprising of almost equal proportion of four subtypes were tested for molecular alterations of SLIT2, ROBO1, ROBO2 and CDC42, the key regulator genes of this pathway. Deletion and methylation frequencies of the candidate genes were seen in the following order: deletion, SLIT2 (38.6%) > ROBO1 (30%) > ROBO2 (7.3%); methylation, SLIT2 (63.3%) > ROBO1 (26.6%) >ROBO2 (9.3%). Majority (80%, 120/150) of the tumours showed alterations (deletion/methylation) in at least one of the candidate genes. Overall, alterations of the candidate genes were as follows: SLIT2, 75.3% (101/150); ROBO1, 45.3% (68/150); ROBO2, 15.3% (23/150). Significantly, higher alteration of SLIT2 locus was observed in triple negative breast cancer (TNBC) over HER2 subtype (P = 0.0014). Similar trend is also seen in overall alterations of SLIT2 and/or ROBO1, in TNBC than HER2 subtype (P = 0.0012); of SLIT2 and/or ROBO2 in TNBC than luminal A (P = 0.014) and HER2 subtype (P = 0.048). Immunohistochemical analysis of SLIT2, ROBO1/2 showed reduced expression, concordant with their molecular alterations. Also, high expression of total CDC42 (49/52; 94.2%) and reduced expression of phospho Serine 71 CDC42 (41/52; 78.8%) was observed. Coalterations of SLIT2 and/or ROBO1, SLIT2 and/or ROBO2 had significant association with reduced expression of phospho Serine-71 CDC42 (P = 0.0012-0.0038). Alterations of SLIT2 and/or ROBO1, reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients. Results indicate the importance of SLIT2-ROBO1-CDC42 signalling pathway in predicting tumour progression. PMID- 27659327 TI - Association of IL-6 and MMP-3 gene polymorphisms with susceptibility to adolescent idiopathic scoliosis: a meta-analysis. AB - Recently, several institutions have investigated the associations of MMP-3-1171 5A/6A and IL-6-174-G/C gene polymorphisms with adolescent idiopathic scoliosis (AIS), while reports from different institutions are not consistent. Therefore, we, comprehensively and systematically performed this meta-analysis to detect whether the two gene polymorphisms are correlated with AIS. From January 1994 to October 2015, all case-control studies focussed on the relationship between the two aforementioned gene polymorphisms and the susceptibility to AIS were retrieved from bibliographic databases. A total of 16 articles were found, of which five consisted of 944 cases and 1177 controls, were finally included after being assessed by two reviewers. We calculated the pooled odds ratio (OR) with 95% confidence interval (95% CI) to assess the associations. The pooled data analyses were based on allele contrast, homozygote, heterozygote, dominant and recessive models. Overall, there was no significant association of IL-6-174-G/C gene polymorphism with AIS risk. Significant association was observed in homozygote model of MMP-3-1171-5A/6A gene polymorphism (5A5A versus 6A6A: OR = 1.69, 95% CI = 1.11-2.58, P = 0.02). When stratified into Caucasian and Asian populations, positive association was found in Caucasian population (5A versus 6A: OR = 1.43, 95% CI = 1.11-1.84, P = 0.006; 5A5A versus 6A6A: OR = 1.90, 95% CI = 1.13-3.19, P = 0.015); however, there was no significant association in Asian population. The present study concluded that 5A5A genotype of MMP-3-1171 5A/6A gene polymorphism was associated with AIS, especially in Caucasian population. However, no significant association was detected between IL-6-174-G/C gene polymorphism and AIS. PMID- 27659328 TI - Molecular cloning, characterization and expression of WAG-2 alternative splicing transcripts in developing spikes of Aegilops tauschii. AB - WAG-2 is a C-class MADS-box gene, which is orthologous to AGAMOUS (AG) in Arabidopsis. The AG group C-class MADS-box genes are involved in stamen and pistil identity. In this study, two WAG-2 transcripts, namely, WAG-2f and WAG- 2g, were isolated and characterized from Aegilops tauschii. The open reading frames of WAG-2f and WAG-2g were 825 and 822 bp, respectively, encoding 275 and 274 amino acid residues. BLAST searches of partial WAG-2 genomic sequence against the draft sequence of Ae. tauschii genome database revealed the complex structure of WAG-2 gene, which consisted of seven exons and six introns. The WAG-2f and WAG 2g cDNAs were two alternative splicing transcripts. The alternative splicing events were produced by an alternative 5' splice site. The expression level of WAG-2f transcript, which was extremely weak in young spikes of floret primordium formation stage, increased as the spikes developed. The highest expression was observed in the spikes at the anther separation stage. Low expression levels of WAG-2f were also detected at the tetrad stage. The WAG- 2g transcript was expressed at all four stages of spike development but at a relatively low level. The expression pattern of the two transcripts was distinctly different during floral development, thereby suggesting a functional divergence. PMID- 27659326 TI - Characterization and expression analyses of the H+-pyrophosphatase gene in rye. AB - The H+-pyrophosphatase (H+-PPase) gene plays an important role in maintaining intracellular proton gradients. Here, we characterized the full-length complementary DNA (cDNA) and DNA of the H+-PPase gene ScHP1 in rye (Secale cereale L. 'Qinling'). We determined the subcellular localization of this gene and predicted the corresponding protein structure. We analysed the evolutionary relationship between ScHP1 and H+-PPase genes in other species, and did real-time quantitative polymerase chain reaction to explore the expression patterns of ScHP1 in rye plants subjected to N, P and K deprivation and to cold, high-salt and drought stresses. ScHP1 cDNA included a 2289 bp open reading frame (ORF) encoding 762 amino acid residues with 14 transmembrane domains. The genomic ScHP1 DNA was 4354 bp and contained eight exons and seven introns. ScHP1 was highly homologous with other members of the H+-PPase gene family. When the full-length ORF was inserted into the expression vector pA7-YFP, the fluorescent microscopy revealed that ScHP1-YFP fusion protein was located in the plasma membrane. Rye plants that were subjected to N deprivation, cold and high-salt stresses, ScHP1 expression was higher in the leaves than roots. Conversely, plants subjected to P and K deprivation and drought stress, ScHP1 expression was higher in the roots than leaves. Under all the investigated stress conditions, expression of ScHP1 was lower in the stem than in the leaves and roots. Our results imply that ScHP1 functions under abiotic stress response. PMID- 27659329 TI - Detecting cognizable trends of gene expression in a time series RNA-sequencing experiment: a bootstrap approach. AB - Study of temporal trajectory of gene expression is important. RNA sequencing is popular in genome-scale studies of transcription. Because of high expenses involved, many time-course RNA sequencing studies are challenged by inadequacy of sample sizes. This poses difficulties in conducting formal statistical tests of significance of null hypotheses. We propose a bootstrap algorithm to identify 'cognizable' 'time-trends' of gene expression. Properties of the proposed algorithm are derived using a simulation study. The proposed algorithm captured known 'time-trends' in the simulated data with a high probability of success, even when sample sizes were small (n < 10). The proposed statistical method is efficient and robust to capture 'cognizable' 'time-trends' in RNA sequencing data. PMID- 27659331 TI - Development and characterization of genic SSR markers from low depth genome sequence of Clarias batrachus (magur). AB - Indian magur (Clarias batrachus) is an important freshwater catfish, which is listed as endangered under A3cde+4acde ver. 3.1 categories by the IUCN (2015) due to decreasing population trend. Microsatellites or short sequence repeats (SSRs) tagged to genes have been utilized as gene marker. In the present study, 31,814 SSRs of C. batrachus (magur) were identified using microsatellite identification tool programme from the next generation sequencing data generated on Roche 454 and Ion Torrent platforms. A bioinformatics pipeline, with stringent criteria resulted in selection of 1672 microsatellite loci falling in the genic region. Initially, a total of 30 loci were selected for primer development; and of these 14 were successfully amplified and five were found to be polymorphic in 30 individuals of C. batrachus (magur). The observed as well as expected heterozygosity ranged from 0.038 to 0.526 and 0.434 to 0.784, respectively, and the number of observed alleles ranged from three to five. The study reported the application of next generation sequencing technologies for rapid development of microsatellite loci in Indian catfish species, C. batrachus (magur). PMID- 27659330 TI - Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity and metabolic phenotypes in a Taiwanese population: a replication study. AB - It is a key challenge to conduct reproducibility in genetic research, especially association studies in obesity. While susceptibility of a single-nucleotide polymorphism (SNP), rs9939609, in the fat mass and obesity-associated (FTO) gene to obesity has been reported in various populations, data from Asians is less conclusive. This replication study was carried out to test whether the FTO rs9939609 SNP is a predictive factor for obesity and obesity-related metabolic traits in a Taiwanese population. A total of 1188 Taiwanese subjects were recruited for this study. The FTO rs9939609 SNP was genotyped by the Taqman assay. Obesity-related metabolic traits such as triglyceride, waist circumference, systolic and diastolic blood pressure, total cholesterol, creatinine, alanine aminotransferase and fasting glucose were measured. Our data revealed that the FTO rs9939609 SNP exhibited a significant association with obesity (BMI >= 30 kg/m2) among the subjects (P = 0.026). However, the FTO rs9939609 SNP did not exhibit any significant association with obesity-related metabolic traits among the subjects. Our results indicated that the FTO rs9939609 SNP may be linked with the risk of obesity in Taiwanese subjects. PMID- 27659332 TI - Effect of matrix metalloproteinase promoter polymorphisms on endometriosis and adenomyosis risk: evidence from a meta-analysis. AB - Matrix metalloproteinase (MMP) promoter polymorphisms are considered to play roles in the aetiology of endometriosis and adenomyosis, however, the evidence available are inconsistent. We aimed to systematically review the asscociation between MMP-1 -1607 1G/2G MMP-2 -735 C/T, MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms and the risk of endometriosis and adenomyosis. A systemic search was conducted in Ovid, PubMed, Chinese National Knowledge Infrastructure and ChineseWanfang Database.We used the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) to calculate the statistical power. Besides, we evaluated the quality of individual studies based on Newcastle-Ottawa scale. A total of 13 papers with 18 studies conformed to our inclusion criteria. We observed a significant association between MMP-1 -1607 1G/2G polymorphism and the susceptibility of endometriosis and adenomyosis under recessive model (OR = 1.25, 95%CI = 1.03-1.53, P = 0.03). While no significant association was found in MMP-2 -735 C/T, MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms. This systemic review and meta-analysis suggested that theMMP-1 -1607 1G/2G polymorphism might play an important role in the risk of endometriosis and adenomyosis. Further, more well-designed and large-scale studies regarding gene gene and gene-environment interactions are needed in the future. PMID- 27659333 TI - Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a child with developmental delay and excessive weight. AB - Prader-Willi syndrome is a rare syndrome characterized by hypotonia, developmental delay and excessive appetite. This syndrome is caused by the loss of function of paternally-expressed genes located in an imprinting centre in 15q11-q13. Here, we report the case of a patient who was referred to us with Prader-Willi syndrome-like symptoms including obesity and developmental delay. Examination of this patient revealed that he was a carrier of a paternally inherited deletion that affected the U1B and U1B* upstream exons of the SNURF SNRNP gene within the 15q11-q13 imprinted region. Mutations localized within this genomic region have not been previously reported in Prader-Willi syndrome patients. It is possible that disruption of upstream exons of SNURF-SNRNP could contribute to Prader-Willi phenotype by disrupting brain-specific alternative transcripts, although, case reports from further patients with a comparable phenotype are required. PMID- 27659335 TI - Genomewide association analysis for awn length linked to the seed shattering gene qSH1 in rice. AB - Awn is one of the most important domesticated traits in rice (Oryza sativa). Understanding the genetic basis of awn length is important for grain harvest and production, because long awn length is disadvantageous for both grain harvest and milling. We investigated the awn length of 529 rice cultivars and performed a Genomewide association studies (GWAS) in the indica and japonica subpopulations, and the whole population. In total, we found 17 loci associated with awn length. Of these loci, seven were linked to previously reported quantitative trait loci, and one was linked to the awn gene An-1. Nine novel loci were repeatedly identified in different environments. One of the nine associations was identified in both the whole and japonica populations. Special interest was the detection of the most significant association SNP, sf0136352825, which was less than 95 kb from the seed shattering gene qSH1. These results may provide potentially favourable haplotypes for molecular breeding in rice. PMID- 27659334 TI - Computational identification and characterization of novel microRNA in the mammary gland of dairy goat (Capra hircus). AB - Many studies have indicated that microRNAs (miRNAs) influence the development of the mammary gland by posttranscriptionally affecting their target genes. The objective of this research was to identify novel miRNAs in the mammary gland of dairy goats with a bioinformatics approach that was based on expressed sequence tag (EST) and genome survey sequence (GSS) analyses. We applied all known major mammals, miRNAs to search against the goat EST and GSS databases for the first time to identify new miRNAs. We, then, validated these newly predicted miRNAs with stem-loop reverse transcription followed by a SYBR Green polymerase chain reaction assay. Finally, 29 mature miRNAs were identified and verified, and of these, 14 were grouped into 13 families based on seed sequence identity and 85 potential target genes of newly verified miRNAs were subsequently predicted, most of which seemed to encode the proteins participating in regulation of metabolism, signal transduction, growth and development. The predicting accuracy of the new miRNAs was 70.37%, which confirmed that the methods used in this study were efficient and reliable. Detailed analyses of the sequence characteristics of the novel miRNAs of the goat mammary gland were performed. In conclusion, these results provide a reference for further identification of miRNAs in animals without a complete genome and thus improve the understanding of miRNAs in the caprine mammary gland. PMID- 27659337 TI - A novel mutation in the AGXT gene causing primary hyperoxaluria type I: genotype phenotype correlation. AB - Primary hyperoxaluria type I (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine : glyoxylate aminotransferase (AGT) which is deficient or mistargeted to mitochondria. PH1 shows considerable phenotypic and genotypic heterogeneity. The incidence and severity of PH1 varies in different geographic regions. DNA samples of the affected members from two unrelated Tunisian families were tested by amplifying and sequencing each of the AGXT exons and intron-exon junctions. We identified a novel frameshift mutation in the AGXT gene, the c.406_410dupACTGC resulting in a truncated protein (p.Gln137Hisfs*19). It is found in homozygous state in two nonconsanguineous unrelated families from Tunisia. These molecular findings provide genotype/phenotype correlations in the intrafamilial phenotypic and permit accurate carrier detection, and prenatal diagnosis. The novel p.Gln137Hisfs*19 mutation detected in our study extend the spectrum of known AGXT gene mutations in Tunisia. PMID- 27659336 TI - Cloning and expression analysis of chalcone synthase gene from Coleus forskohlii. AB - Flavonoids are an important class of secondary metabolites that play various roles in plants such as mediating defense, floral pigmentation and plant-microbe interaction. Flavonoids are also known to possess antioxidant and antimicrobial activities. Coleus forskohlii (Willd.) Briq. (Lamiaceae) is an important medicinal herb with a diverse metabolic profile, including production of a flavonoid, genkwanin. However, components of the flavonoid pathway have not yet been studied in this plant. Chalcone synthase (CHS) catalyses the first committed step of flavonoid biosynthetic pathway. Full-length cDNA, showing homology with plant CHS gene was isolated from leaves of C. forskohlii and named CfCHS (GenBank accession no. KF643243). Theoretical translation of CfCHS nucleotide sequence shows that it encodes a protein of 391 amino acids with a molecular weight of 42.75 kDa and pI 6.57. Expression analysis of CfCHS in different tissues and elicitor treatments showed that methyl jasmonate (MeJA) strongly induced its expression. Total flavonoids content and antioxidant activity of C. forskohlii also got enhanced in response to MeJA, which correlated with increased CfCHS expression. Induction of CfCHS by MeJA suggest its involvement in production of flavonoids, providing protection from microbes during herbivory or mechanical wounding. Further, our in silico predictions and experimental data suggested that CfCHS may be posttranscriptionally regulated by miR34. PMID- 27659338 TI - Prevalence of common MEFV mutations and carrier frequencies in a large cohort of Iranian populations. AB - Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder caused by mutations in the MEFV gene. The disease is especially common among Armenian, Turkish, Jewish and Middle East Arab populations. To identify the frequency and the spectrum of common MEFV mutations in different Iranian populations, we investigated a cohort of 208 unselected asymptomatic individuals and 743 FMF patients. Nine hundred and fifty-one samples were analysed for the presence of 12 MEFV mutations by PCR and reverse-hybridization (FMF StripAssay, ViennaLab, Vienna, Austria). Confirmatory dideoxy sequencing of all MEFV gene exons was performed for 39 patients. Fifty-seven (27.4%) healthy individual carried mutant MEFV alleles. Three hundred and ninety-one (52.6%) FMF patients were found positive for either one (172/743; 23.1%), two or three MEFV mutations. Using dideoxy sequencing, three novel variants, A66P, R202W and H300Q, could be identified. Our analysis revealed an allele frequency and carrier rate of 15.6 and 27.4%, respectively, among healthy Iranians. Still moderate compared to neighbouring Armenia, but higher than in Turkey or Iraq, these data suggest that FMF is remarkably common among Iranian populations. E148Q was most frequent in the group of healthy individuals, whereas M694V was the most common mutation among FMF patients, thereby corroborating previous studies on MEFV mutational spectra in the Middle East. Accordingly, MEFV mutations are frequent in healthy Iranian individuals across different ethnic groups. Based on this finding, the awareness for FMF and the implementation of augmented carrier screening programmes considering the multiethnic nature of the Iranian population should be promoted. PMID- 27659339 TI - Genetic diversity of bitter taste receptor gene family in Sichuan domestic and Tibetan chicken populations. AB - The sense of bitter taste plays a critical role in animals as it can help them to avoid intake of toxic and harmful substances. Previous research had revealed that chicken has only three bitter taste receptor genes (Tas2r1, Tas2r2 and Tas2r7). To better understand the genetic polymorphisms and importance of bitter taste receptor genes (Tas2rs) in chicken, here, we sequenced Tas2rs of 30 Sichuan domestic chickens and 30 Tibetan chickens. Thirteen single-nucleotide polymorphisms (SNPs) including three nonsynonymous mutations (m.359G>C, m.503C>A and m.583A>G) were detected in Tas2r1 (m. is the abbreviation for mutation); three SNPs were detected in Tas2r2, but none of them were missense mutation; eight SNPs were detected in Tas2r7 including six nonsynonymous substitutions (m.178G>A, m.421A>C, m.787C>T, m.832G>T, m.907A>T and m.943G>A). Tajima's D neutral test indicates that there is no population expansion in both populations, and the size of the population is relatively stable. All the three networks indicate that red jungle fowls share haplotypes with domestic chickens. In addition, we found that haplotypes H1 and HE1 were positively associated with high-altitude adaptation, whereas haplotypes H4 and HE4 showed a negative correlation with high-altitude adaptation in Tas2rs. Although, chicken has only three Tas2rs, our results showed that both Sichuan domestic chickens and Tibetan chickens have abundant haplotypes in Tas2rs, especially in Tas2r7, which might help chickens to recognize a wide variety of bitter-tasting compounds. PMID- 27659340 TI - Characterization and tissue distribution of Lhx9 and Lhx9alpha in Chinese giant salamander Andrias davidianus. AB - Lhx9 is an LIM (named for the first three proteins in which the domain was found, Lin-11, Isl1 and Mec-3) homeodomain protein involved in development and differentiation of the gonad. In this study, we isolated the full-length Lhx9 and Lhx9alpha from Andrias davidianus, detected the tissue distribution and analysed the methylation of the promoters. We identified Lhx9 of 1411 bp and Lhx9alpha of 1153-bp length, differing in the 3'-flanking region, encoding 399 and 330 amino acids, respectively. The Lhx9 gene was detected primarily in liver, ovary and heart with moderate expression in brain, pituitary, intestine and spleen, and low expression in the remaining examined tissues, while Lhx9alpha expression was high in heart, pituitary and liver, and low in spleen and stomach. Significantly higher Lhx9 expression was observed in ovary than in testis, with no differences in Lhx9alpha expression between testis and ovary observed. Bisulphite sequencing revealed significantly higher methylation in testis compared to ovary. The methylation level of CpG sites -733, -673, -615 and -594 exhibited significantly higher levels in testis than in ovary, which was negatively correlated with Lhx9 expression. The methylation and expression patterns suggested that promoter methylation suppressed expression of Lhx9 in A. davidianus. PMID- 27659342 TI - Gene actions for yield and its attributes and their implications in the inheritance pattern over three generations in opium poppy (Papaver somniferum L.). AB - The gene actions for yield and its attributes and their inheritance pattern based on five parameter model have been explored in four single crosses (NBIHT-5 * NBIHT-6, NBIHT-5 * NBMHT-1, NBMHT-1 * NBIHT-6 and NBMHT-2 * NBMHT-1) obtained using thebaine rich pure lines of opium poppy (Papaver somniferum L.) for three consecutive generations. All the traits showed nonallelic mode of interaction, however, dominance effect (h) was more pronounced for all the traits except thebaine and papaverine. The dominance * dominance (l) effects were predominant over additive * additive (i) for all traits in all the four crosses except for papaverine. The seed and opium yield, and its contributing traits inherited quantitatively. The fixable gene effects (d) and (i) were lower in magnitude than nonfixable (h) and (l) gene effects. The estimates of heterosis were also higher in comparison to the respective parents which suggested preponderance of dominance gene action for controlling most of the traits. The phenotypic coefficient of variation was marginally higher than those of genotypic coefficient of variation for all the traits. The traits thebaine, narcotine, morphine and opium yield had high heritability coupled with high genetic advance. The leaf number, branches per plant and stem diameter showed positive correlation with opium and seed yields. The selection of plants having large number of leaves, branches and capsules with bigger size would be advantageous to enhance the yield potential. PMID- 27659341 TI - Genomewide analysis of MATE-type gene family in maize reveals microsynteny and their expression patterns under aluminum treatment. AB - Multidrug and toxic compound extrusion (MATE) proteins are a group of secondary active transporters, which widely exist in all living organisms and play important role in the detoxication of endogenous secondary metabolites and exogenous agents. However, to date, no systematic and comprehensive study of this family is reported in maize. Here, a total of 49 MATE genes (ZmMATE) were identified and divided into seven groups by phylogenetic analysis. Conserved intro-exon structures and motif compositions were investigated in these genes. Results by gene locations indicated that these genes were unevenly distributed among all 10 chromosomes. Tandem and segmental duplications appeared to contribute to the expansion and evolution of this gene family. The Ka/Ks ratios suggested that the ZmMATE has undergone large-scale purifying selection on the maize genome. Interspecies microsynteny analysis revealed that there were independent gene duplication events of 10 ZmMATE. In addition, most maize MATE genes exhibited different expression profiles in diverse tissues and developmental stages. Sixteen MATE genes were chosen for further quantitative real-time polymerase chain reaction analysis showed differential expression patterns in response to aluminum treatment. These results provide a useful clue for future studies on the identification of MATE genes and functional analysis of MATE proteins in maize. PMID- 27659343 TI - Enhancement of larval immune system traits as a correlated response to selection for rapid development in Drosophila melanogaster. PMID- 27659344 TI - Paternal social experience affects male reproductive behaviour in Drosophila melanogaster. PMID- 27659345 TI - Lack of association between rs10491334 in the CAMK4 gene and longevity in a Chinese population. PMID- 27659346 TI - Genetic diversity in barley landraces (Hordeum vulgare L. subsp.vulgare) originated from Crescent Fertile region as detected by seed storage proteins. PMID- 27659348 TI - Upregulation of the C/EBP beta LAP isoform could be due to decreased TNFAIP3/TNIP1 expression in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus. AB - OBJECTIVES: We aimed to examine CCAAT/enhancer-binding protein beta (C/EBP beta), TNF-alpha-induced protein 3 (TNFAIP3), and TNFAIP3-interacting protein 1 (TNIP1) expression in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients to assess their relationship in SLE pathogenesis. METHODS: C/EBP beta, TNIP1, and TNFAIP3 expression was assessed in PBMCs from 20 SLE patients and 20 controls by western blotting. The correlation between C/EBP beta/TNFAIP3/TNIP1 expression and SLE disease activity was determined by Spearman's rank. C/EBP beta, TNIP1, and TNFAIP3 levels in THP-1 cells, THP-1 cells transfected with plasmids encoding TNFAIP3 shRNA, and THP-1 cells infected with lentiviral vectors encoding TNIP1 shRNA were assessed by western blotting. RESULTS: C/EBP beta LAP isoform expression was increased and LIP/TNFAIP3/TNIP1 expression was decreased in SLE patients. LAP expression was positively correlated with SLE disease activity; TNFAIP3 and TNIP1 expression was negatively correlated with SLE disease activity. LAP expression was increased in SLE patients with proteinuria and elevated anti-dsDNA antibody, as well as in THP-1 cells transfected with plasmids encoding TNFAIP3 shRNA and THP-1 cells infected with lentiviral vectors encoding TNIP1 shRNA. CONCLUSIONS: C/EBP beta/TNFAIP3/TNIP1 is associated with SLE activity. The upregulated expression of C/EBP beta LAP could be caused by reduced TNFAIP3/TNIP1 expression. PMID- 27659349 TI - Blood lead concentrations and attention deficit hyperactivity disorder in Korean children: a hospital-based case control study. AB - BACKGROUND: Because the developing brain of a child is vulnerable to environmental toxins, even very low concentration of neurotoxin can affect children's neurodevelopment. Lead is a neurotoxic heavy metal which has the harmful effect on the striatal-frontal circuit of brain. This area of the brain is known to be closely related to attention deficit hyperactivity disorder (ADHD) pathophysiology. The primary objective of the present study was to investigate whether elevated blood lead concentration is a risk factor for ADHD. The secondary objective was to examine the association between blood lead concentration and symptom severity. METHODS: We conducted a frequency-matched, hospital-based case-control study with 114 medically diagnosed ADHD cases and 114 controls. The participants were matched for age and sex. The diagnoses of ADHD were assessed with semi-structured diagnostic interviews. The participants completed the continuous performance test (CPT), and their parents completed the ADHD-rating scale (ADHD-RS). Blood lead concentrations were measured by using graphite furnace atomic absorption spectrometry featuring Zeeman background correction. RESULTS: Children with ADHD exhibited blood lead concentrations that were significantly higher than those of the controls ( 1.90 +/- 086 MUg/dl vs. 1.59 +/- 0.68 MUg/dl, p = 0.003). The log transformed total blood lead concentration was associated with a higher risk of ADHD (OR: 1.60, 95 % CI: 1.04 2.45, p < 0.05). The analysis also revealed that the children with blood lead concentrations above 2.30 MUg/dl were at a 2.5-fold (95 % CI: 1.09-5.87, p < 0.05) greater risk of having ADHD. After adjusting for covariates, our multivariate regression models indicated that blood lead concentrations were not significantly associated with ADHD-RS or CPT profiles among the ADHD cases. CONCLUSION: Even low blood lead concentrations are a risk factor for ADHD in children. This study warrants primary prevention policies to reduce the environmental lead burden. Future studies may be required to ascertain the effects of lead on symptom severity in ADHD. PMID- 27659347 TI - Comparative analysis of gene expression profiles of OPN signaling pathway in four kinds of liver diseases. AB - To explore the relevance of OPN signalling pathway to the occurrence and development of nonalcoholic fatty liver disease (NAFLD), liver cirrhosis (LC), hepatic cancer (HC) and acute hepatic failure (AHF) at transcriptional level, Rat Genome 230 2.0 Array was used to detect expression profiles of OPN signalling pathway-related genes in four kinds of liver diseases. The results showed that 23, 33, 59 and 74 genes were significantly changed in the above four kinds of liver diseases, respectively. H-clustering analysis showed that the expression profiles of OPN signalling-related genes were notably different in four kinds of liver diseases. Subsequently, a total of above-mentioned 147 genes were categorized into four clusters by k-means according to the similarity of gene expression, and expression analysis systematic explorer (EASE) functional enrichment analysis revealed that OPN signalling pathway-related genes were involved in cell adhesion and migration, cell proliferation, apoptosis, stress and inflammatory reaction, etc. Finally, ingenuity pathway analysis (IPA) software was used to predict the functions of OPN signalling-related genes, and the results indicated that the activities of ROS production, cell adhesion and migration, cell proliferation were remarkably increased, while that of apoptosis, stress and inflammatory reaction were reduced in four kinds of liver diseases. In summary, the above physiological activities changed more obviously in LC, HC and AHF than in NAFLD. PMID- 27659350 TI - Comparison Over Time of Vault in Chinese Eyes Receiving Implantable Contact Lenses With or Without a Central Hole. AB - PURPOSE: To compare the longitudinal vault changes after implantation of a posterior chamber phakic intraocular lens (pIOL) (Visian implantable contact lens) with (ICL V4c) and without (ICL V4) a central artificial hole for moderate to high myopia in Chinese eyes. DESIGN: Retrospective case series. METHODS: This study comprised 78 eyes implanted with the ICL V4c model and 82 eyes implanted with the ICL V4 model at our department by the same surgeon. The time course of the postoperative pIOL vault changes was quantitatively assessed using ultrasound biomicroscopy over 6 months. RESULTS: There was a trend toward a decrease in all measures of central vault, peripheral vault, and the endothelium-anterior pIOL distance for both central hole pIOL and conventional pIOL over time, although the variance was not statistically significant (all P > .05). There were no significant between-group differences in the amount of the pIOL central vault, peripheral vault, or the endothelium-anterior pIOL distance at any time point after surgery (all P > .05). CONCLUSIONS: The time course of the central hole pIOL vault changes is essentially equivalent to that of the conventional pIOL vault, suggesting that the presence of the central hole did not significantly affect the pIOL position. PMID- 27659352 TI - Automated signal quality assessment of mobile phone-recorded heart sound signals. AB - Mobile phones, due to their audio processing capabilities, have the potential to facilitate the diagnosis of heart disease through automated auscultation. However, such a platform is likely to be used by non-experts, and hence, it is essential that such a device is able to automatically differentiate poor quality from diagnostically useful recordings since non-experts are more likely to make poor-quality recordings. This paper investigates the automated signal quality assessment of heart sound recordings performed using both mobile phone-based and commercial medical-grade electronic stethoscopes. The recordings, each 60 s long, were taken from 151 random adult individuals with varying diagnoses referred to a cardiac clinic and were professionally annotated by five experts. A mean voting procedure was used to compute a final quality label for each recording. Nine signal quality indices were defined and calculated for each recording. A logistic regression model for classifying binary quality was then trained and tested. The inter-rater agreement level for the stethoscope and mobile phone recordings was measured using Conger's kappa for multiclass sets and found to be 0.24 and 0.54, respectively. One-third of all the mobile phone-recorded phonocardiogram (PCG) signals were found to be of sufficient quality for analysis. The classifier was able to distinguish good- and poor-quality mobile phone recordings with 82.2% accuracy, and those made with the electronic stethoscope with an accuracy of 86.5%. We conclude that our classification approach provides a mechanism for substantially improving auscultation recordings by non-experts. This work is the first systematic evaluation of a PCG signal quality classification algorithm (using a separate test dataset) and assessment of the quality of PCG recordings captured by non-experts, using both a medical-grade digital stethoscope and a mobile phone. PMID- 27659351 TI - Reproducibility of NIRS assessment of muscle oxidative capacity in smokers with and without COPD. AB - Low muscle oxidative capacity contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Near-infrared spectroscopy (NIRS) allows non-invasive determination of the muscle oxygen consumption (mVO2) recovery rate constant (k), which is proportional to oxidative capacity assuming two conditions are met: 1) exercise intensity is sufficient to fully-activate mitochondrial oxidative enzymes; 2) sufficient O2 availability. We aimed to determine reproducibility (coefficient of variation, CV; intraclass correlation coefficient, ICC) of NIRS k assessment in the gastrocnemius of 64 participants with (FEV1 64+/-23%predicted) or without COPD (FEV1 98+/-14%predicted). 10-15s dynamic contractions preceded 6min of intermittent arterial occlusions (5-10s each, ~250mmHg) for k measurement. k was lower (P<0.05) in COPD (1.43+/-0.4min-1; CV=9.8+/-5.9%, ICC=0.88) than controls (1.74+/-0.69min-1; CV=9.9+/-8.4%; ICC=0.93). Poor k reproducibility was more common when post-contraction mVO2 and deoxygenation were low, suggesting insufficient exercise intensity for mitochondrial activation and/or the NIRS signal contained little light reflected from active muscle. The NIRS assessment was well tolerated and reproducible for muscle dysfunction evaluation in COPD. PMID- 27659353 TI - Immunogenic FEAT protein circulates in the bloodstream of cancer patients. AB - BACKGROUND: FEAT is an intracellular protein that potently drives tumorigenesis in vivo. It is only weakly expressed in normal human tissues, including the testis. In contrast, FEAT is aberrantly upregulated in most human cancers. The present study was designed to investigate whether FEAT is applicable to tumor immunotherapy and whether FEAT is discernible in the bloodstream as a molecular biomarker of human cancers. METHODS: Two mouse FEAT peptides with predicted affinities for major histocompatibility complex H-2Kb and H-2Db were injected subcutaneously into C57BL/6 mice before subcutaneous transplantation of isogenic B16-F10 melanoma cells. Intracellular localization of FEAT was determined by immunogold electron microscopy. Immunoprecipitation was performed to determine whether FEAT was present in blood from cancer patients. A sandwich enzyme-linked immunosorbent assay was used to measure FEAT concentrations in plasma from 30 cancer patients and eight healthy volunteers. RESULTS: The vaccination experiments demonstrated that FEAT was immunogenic, and that immune responses against FEAT were induced without deleterious side effects in mice. Electron microscopy revealed localization of FEAT in the cytoplasm, mitochondria, and nucleus. Immunoprecipitation identified FEAT in the blood plasma from cancer patients, while FEAT was not detected in plasma exosomes. Plasma FEAT levels were significantly higher in the presence of cancers. CONCLUSIONS: These findings suggest that FEAT is a candidate for applications in early diagnosis and prevention of some cancers. PMID- 27659354 TI - The risk of cardiovascular side effects with anti-anginal drugs. AB - INTRODUCTION: Angina pectoris is a common presenting symptom of underlying coronary artery disease or reduced coronary flow reserve. Patients with angina have impaired quality of life; and need to be treated optimally with antianginal drugs to control symptoms and improve exercise performance. A wide range of antianginal medications are approved for the treatment of angina, and often more than one class of antianginal drugs are used to adequately control the symptoms. This expert opinion highlights the likely cardiac adverse effects of available antianginal drugs, and how to minimize these in individual patients and especially during combination treatment. Areas covered: All approved antianginal drugs, including the older and newly approved medications with different mechanism of action to the older drugs as well as some of the unapproved herbal medications. The safety profiles and potential cardiac side effects of these medications when used as monotherapy or as combination therapy are discussed and highlighted. Expert opinion: Because of the different cardiac safety profiles and possible side effects, we recommend selection of initial drug or adjustment of therapy based on the resting heart rate; blood pressure, hemodynamic status; and resting left ventricular function, concomitant medications and any associated comorbidities. PMID- 27659355 TI - L-shaped nipple reconstruction. PMID- 27659356 TI - The association of level of practical experience in transrectal ultrasonography guided prostate biopsy with its diagnostic outcome. AB - INTRODUCTION The diagnostic yield of transrectal ultrasonography (TRUS) guided prostate biopsy is influenced by many patient and procedure specific factors. However, the role of operator specific factors remains inadequately defined. This study investigated the association of diagnostic outcome of TRUS guided biopsy with operator skill level. METHODS This study looked at a consecutive cohort of 690 men undergoing their first extended pattern TRUS guided prostate biopsy by 27 operators over a 24-month period in a single institution. Logistic regression was used for statistical analysis. RESULTS Biopsies performed by consultants (odds ratio [OR]: 2.35, p=0.004) and senior trainees (OR: 2.37, p=0.002) in patients with prostate specific antigen levels of <10ng/ml were more likely to be positive than those performed by junior trainees (cancer detection rate 50.0%, 50.3% and 29.9% respectively). Furthermore, biopsies performed by junior trainees yielded a significantly higher proportion of prostate cancers with a Gleason score of >=3+4 than those performed by senior trainees (OR: 2.11, p=0.031) and consultants (OR: 2.40, p=0.013) (81.4%, 67.5% and 64.6% respectively). No significant differences emerged between operator skill groups for complications, rebiopsy rates or the number of prostate cancers found during the follow-up period (median: 34 months) of patients with a negative biopsy. CONCLUSIONS Level of operator experience is associated with the diagnostic outcome of extended pattern TRUS guided biopsy. The findings of this study imply that case selection, self-audit and expert supervision for the duration of the learning curve should form the basis of biopsy training. PMID- 27659358 TI - Spontaneous haemorrhage from a left gastric artery aneurysm as a cause of acute abdominal pain. AB - Visceral artery aneurysms are rare, with a reported incidence of less than 2% in the general population. 1,2 Aneurysms of the left gastric artery are particularly uncommon, accounting for 4% of all visceral aneurysms. 3,4 Although the majority are discovered incidentally and can be managed conservatively, prompt treatment of those ruptured or at risk of rupture is crucial to reduce the associated morbidity. Increasing awareness of visceral artery aneurysms as a cause of spontaneous intraperitoneal haemorrhage will improve early recognition and impact on survival. We present a rare case of spontaneous rupture of a left gastric artery aneurysm. PMID- 27659357 TI - Usefulness of chemoradiotherapy for inoperable gastric cancer. AB - Introduction Radiotherapy is not commonly used for the treatment of gastric cancer in Japan, where surgery is the standard local treatment. We report the results of chemoradiotherapy in patients with advanced or recurrent gastric cancer which was deemed difficult to treat surgically. Methods Twenty-one patients with gastric cancer (including sixteen with advanced/recurrent gastric cancer and five with poor general condition) underwent chemo-radiotherapy, for whom the therapeutic efficacy, toxicity and survival period were analysed. Results The tumour response to chemoradiotherapy was categorised as complete, partial, stable or progressive in 5, 9, 3, and 4 patients, respectively, with an overall response rate of 67%. No serious complications such as gastrointestinal perforation or bleeding occurred, and no cardiac, hepatic or renal dysfunction developed during the follow-up period. The mean survival time was 19.8 months (range, 3-51 months). One patient died of another disease, 18 died of primary cancer and the cause of death was unknown in 2 patients. Conclusions Chemoradiotherapy appears to be an effective treatment for localised gastric cancer without distant metastases, but further studies are needed to determine the indications for chemoradiotherapy and late adverse effects, as well as the chemotherapy regimens to be used. PMID- 27659360 TI - A cadaveric study showing the anatomical variations in the branches of the dorsalis pedis artery at the level of the ankle joint and its clinical implication in ankle arthroscopy. AB - Introduction Pseudoaneurysm formation following ankle arthroscopy is a rare but potentially catastrophic complication. The placement of anterior ankle portals carries inherent risk to the superficial and deep peroneal nerves, as well as to the dorsalis pedis artery. Anatomical variations in the dorsalis pedis and the presence of branches at the joint line may increase the risk of vascular injury and pseudoaneurysm formation during arthroscopy. There is limited anatomical evidence available regarding the branches of the dorsalis pedis artery, which occur at the point at which they cross the ankle joint. Objectives The objective of the study was to describe the frequency and direction of branches of the dorsalis pedis crossing the ankle joint. Materials and Methods Nineteen cadaveric feet were carefully dissected to explore the course of the dorsalis pedis artery, noting in particular the branching pattern at the joint line. Results Eleven of the nineteen feet had a branch of the dorsalis pedis artery that crossed the level of the ankle joint. Out of these, six were lateral, four medial and one bilateral. Eight of the eleven specimens had one branch at, or just before, the level of the joint. Two specimens had two branches and one had three branches crossing the ankle, which were all in the same direction, crossing laterally to the main trunk of the dorsalis pedis. Conclusions Our study demonstrated high rates of branching of the dorsalis pedis artery at the level of the ankle joint. The role of these branches in pseudoaneurysm formation during anterior hindfoot surgery remains unclear. PMID- 27659361 TI - Intraoperative use of a tablet computer to aid rhinoplasty. AB - Open septorhinoplasty enables excellent exposure to the structural components of the nasal tip. Nevertheless, it runs the risk of weakening its support mechanisms, which can lead to notable changes to tip projection and rotation as well as to the nasolabial angle. It is therefore paramount that the surgeon reconstructs the nose to the desired endpoint at the end of the operation. Currently, the gold standard of care in rhinoplasty uses preoperative photographs with the patient sitting or standing. However, this is not a true representation of the face in the operative position as the patient is placed supine and so gravity affects the appearance of the nose in a different way. Other factors such as head drapes and traction on the endotracheal tube can also cause subtle changes. We therefore advocate additional intraoperative profile view photographs to improve the accuracy of nasal tip positioning. In our department, in addition to standard preoperative photographs, immediate preoperative profile photos are taken with the patient supine, intubated and draped. Images are captured using a tablet computer at a distance of 1 meter from the patient. We ensure that the Frankfort plane is perpendicular to the floor. The picture is enlarged so that the image is full scale and the tablet is subsequently placed immediately behind the patient for direct comparison. This is then used during the procedure to check tip projection and rotation as well as at the end of the procedure following closure of the columellar incision to ensure correct placement of the nasal tip. PMID- 27659359 TI - The management of colonic trauma in the damage control era. AB - INTRODUCTION The purpose of this study was to audit our current management of colonic trauma, and to review our experience of colonic trauma in patients who underwent initial damage control (DC) surgery. METHODS All patients treated for colonic trauma between January 2012 and December 2014 by the Pietermaritzburg Metropolitan Trauma Service were included in the study. Data reviewed included mechanism of injury, method of management (primary repair [PR], primary diversion [PD] or DC) and outcome (complications and mortality rate). Results A total of 128 patients sustained a colonic injury during the study period. Ninety-seven per cent of the injuries were due to penetrating trauma. Of these cases, 56% comprised stab wounds (SWs) and 44% were gunshot wounds (GSWs). Management was by PR in 99, PD in 20 and DC surgery in 9 cases. Among the 69 SW victims, 57 underwent PR, 9 had PD and 3 required a DC procedure. Of the 55 GSW cases, 40 were managed with PR, 9 with PD and 6 with DC surgery. In the PR group, there were 16 colonic complications (5 cases of breakdown and 11 of wound sepsis). Overall, nine patients (7%) died. CONCLUSIONS PR of colonic trauma is safe and should be used for the majority of such injuries. Persistent acidosis, however, should be considered a contraindication. In unstable patients with complex injuries, the optimal approach is to perform DC surgery. In this situation, formal diversion is contraindicated, and the injury should be controlled and dropped back into the abdomen at the primary operation. At the repeat operation, if the physiological insult has been reversed, then formal repair of the colonic injury is acceptable. PMID- 27659362 TI - Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. AB - Introduction Follicular thyroid cancer (FTC) has a good prognosis if treated early. The aim of this study was to look at the difference in outcomes in those who presented with metastasis early or late in their disease. Methods A retrospective cohort study was conducted of patients diagnosed with FTC (n=91) treated between 2000 and 2013. Demographic, laboratory, pathological and survival data were collected and analysed. Results Metastatic FTC was diagnosed in 20 cases (22%). The median age at diagnosis was 65 years (range: 17-86 years) and 65% of the patients were female. Twelve patients (60%) were diagnosed with metastatic disease at presentation, with the bones being the most common site (75%). In the remaining eight cases (40%), metastasis developed at a median of 4.5 years (range: 2-8 years) after initial thyroid surgery, lungs being the most common site (50%). Eighteen patients (90%) underwent surgical intervention for the primary disease. Sixteen patients (80%) received adjuvant radioactive iodine and eight (40%) received external beam radiotherapy. Widely invasive follicular cancer was the predominant histological diagnosis (90%). No prognostic association was observed with any of the parameters studied. The overall disease specific mortality rate was 40%. There was no significant difference in mortality between those who presented with metastatic disease and those who developed metastasis during the follow-up period (33% vs 50%, p=0.61). Conclusions The clinical outcome and prognosis for cases with metastatic disease is generally poor. Despite this, almost half of the patients in our study were still alive at a median follow-up of 5.5 years, regardless of whether they were diagnosed with metastatic disease on initial presentation or whether they developed metastasis after initial thyroid surgery. PMID- 27659363 TI - Liberal perioperative fluid administration is an independent risk factor for morbidity and is associated with longer hospital stay after rectal cancer surgery. AB - INTRODUCTION Recent studies have advocated the use of perioperative fluid restriction in patients undergoing major abdominal surgery as part of an enhanced recovery protocol. Series reported to date include a heterogenous group of high- and low-risk procedures but few studies have focused on rectal cancer surgery alone. The aim of this study was to assess the effects of perioperative fluid volumes on outcomes in patients undergoing elective rectal cancer resection. METHODS A prospectively maintained database of patients with rectal cancer who underwent elective surgery over a 2-year period was reviewed. Total volume of fluid received intraoperatively was calculated, as well as blood products required in the perioperative period. The primary outcome was postoperative morbidity (Clavien-Dindo grade I-IV) and the secondary outcomes were length of stay and major morbidity (Clavien-Dindo grade III-IV). RESULTS Over a 2-year period (2012-2013), 120 patients underwent elective surgery with curative intent for rectal cancer. Median total intraoperative fluid volume received was 3680ml (range 1200-9670ml); 65/120 (54.1%) had any complications, with 20/120 (16.6%) classified as major (Clavien-Dindo grade III-IV). Intraoperative volume >3500ml was an independent risk factor for the development of postoperative all-cause morbidity (P=0.02) and was associated with major morbidity (P=0.09). Intraoperative fluid volumes also correlated with length of hospital stay (Pearson's correlation coefficient 0.33; P<0.01). CONCLUSIONS Intraoperative fluid infusion volumes in excess of 3500ml are associated with increased morbidity and length of stay in patients undergoing elective surgery for rectal cancer. PMID- 27659364 TI - Hip fracture litigation: A 10-year review of NHS Litigation Authority data and the effect of national guidelines. AB - We present a review evaluating all litigation claims relating to hip fractures made in a 10-year period between 2005 and 2015. Data was obtained from the NHS Litigation Authority through a freedom of information request. All claims relating to hip fractures were reviewed. During the period analysed, 216 claims were made, of which 148 were successful (69%). The total cost of settling these claims was in excess of L5 million. The introduction of a best-practice tariff by the Department of Health in 2010 was designed to improve the quality of care for hip fracture patients. This was followed by guidance from the National Institute for Health and Clinical Excellence in 2011 and the British Orthopaedic Association in 2012. We analysed claims submitted before and after these guidelines were introduced and no significant difference in the number of claims was noted. The most common cause for litigation was a delay in diagnosis, which accounted for 86 claims in total (40%). Despite the presence of these guidelines and targets, there has not been a significant reduction in the number of claims or an improvement in diagnostic accuracy. This may be due to an increasing level of litigation in the UK but we must also question whether we are indeed providing best-practice care to our hip fracture patients and whether these guidelines need further review. PMID- 27659366 TI - Pseudohyperkalaemia: a rare complication of splenectomy. AB - Pseudohyperkalaemia is an uncommon and frequently unrecognised biochemical abnormality. It occurs as a consequence of aggregation and lysis of platelets in vitro. As a result, potassium is released, which causes an elevated serum concentration. We present the case of a 21-year-old man with a traumatic splenic injury necessitating laparotomy and splenectomy. Following surgery he developed hyperkalaemia. Further investigations diagnosed pseudohyperkalaemia, one of the causes of which is thrombocytosis secondary to splenectomy. PMID- 27659365 TI - Radiopathological features predictive of involved margins in ductal carcinoma in situ. AB - INTRODUCTION Ductal carcinoma in situ (DCIS) usually manifests as microcalcification on mammography but may be uncalcified. Consequently, a quarter of patients undergoing excision of a presumed pure DCIS require further surgery to re-excise margins. Patients at highest risk of margin involvement may benefit from additional preoperative assessment. METHODS A retrospective review was carried out of patients treated for screen detected, biopsy proven DCIS in a single centre over a ten-year period (1999-2009). Logistic regression analysis identified factors predictive of need for further surgery to clear margins. RESULTS Overall, 248 patients underwent surgery for DCIS (low/intermediate grade: 82, high grade: 155) and 49 (19.8%) required further surgery. High grade disease was associated with greater mammographic extent (mean: 32mm [range: 5-120mm] vs 25mm [range: 2-100mm]), p=0.009) and higher incidence of mastectomy (38% vs 24%, p=0.034). Factors predictive of involvement of surgical margins necessitating further surgery included negative oestrogen receptor status (OR: 5.2, 95% CI: 2.1 12.8, p<0.001) and mammographic extent (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.2-2.1, p=0.004). Once size exceeded 30mm, more than 50% of patients required secondary breast surgery for margins. CONCLUSIONS Reoperation rates for DCIS increase with preoperative size on mammography and negative oestrogen receptor status on core biopsy. Patients with these risk features should be counselled accordingly and consideration should be given to the role of additional preoperative imaging. PMID- 27659367 TI - A bow-tie for hand trauma. PMID- 27659368 TI - Risk factors for intramedullary nail breakage in proximal femoral fractures: a 10 year retrospective review. AB - INTRODUCTION Intramedullary nailing is a common treatment for proximal femoral fractures. Fracture of the nail is a rare but devastating complication that exposes often frail patients to complex revision surgery. We investigated which risk factors predict nail failure. METHODS We reviewed all cases of nail breakage seen over a 10-year period in a single busy trauma unit; 22 nail fractures were seen in 19 patients. Comparison was made with a group of 209 consecutive patients who underwent intramedullary fixation of a proximal femur fracture with no nail breakage over a 2-year period. RESULTS In the fractured nail group, mean age was 70.4 years (range 55-88 years).The mean time to fracture was 10 months (range 2.5 23 months). Logistical regression was used to show that low American Society of Anesthesiologists (ASA) score, subtrochanteric fracture and pathological fracture were independent risk factors for nail fracture. CONCLUSIONS Young patients with a low ASA score are at highest risk of nail breakage. We advise close follow-up of patients with these risk factors until bony union has been achieved. In addition, there may be merit in considering other treatment options, such as proximal femoral replacement, especially for those with pathological fracture with a good prognosis. PMID- 27659369 TI - The construction and implementation of a clinical decision-making algorithm reduces the cost of adult fracture clinic visits by up to L104,800 per year: a quality improvement study. AB - INTRODUCTION Inappropriate referrals to the new patient fracture clinic unnecessarily consume hospital resources and many hospitals lack clear guidelines as to what should be referred. Many of these injuries can be definitively managed by the emergency department. Our aim was to construct and disseminate a clinical decision-making algorithm to reduce the frequency of inappropriate referrals to fracture clinics at our institution, to improve the management of patients with minor injuries and save the hospital and the patient the cost of unnecessary visits. MATERIALS AND METHODS Data were prospectively collected for all new fracture clinic referrals over two separate 1-week cycles with cohorts of 94 and 74 patients, respectively. After the first cycle, the referral algorithm was disseminated both electronically (intranet) and orally (presentations to emergency department staff). The results of this intervention were examined in the second cycle, which took place 6 months after the first cycle. RESULTS The introduction of this algorithm significantly reduced inappropriate referrals by almost 20% (P = 0.0445). DISCUSSION This simple intervention highlighted a potential annual cost saving of up to L104,000. We advocate the use of this concise algorithm in improving the efficiency of the referral system to fracture clinics. PMID- 27659370 TI - Anatomical siting of the splenic flexure using computed tomography. AB - INTRODUCTION Often, left-sided colorectal surgery requires splenic flexure mobilisation (SFM) to allow a tension-free anastomosis to be carried out. This step is difficult and not without risk. We investigated a system of anatomical siting of the splenic flexure using computed tomography (CT). METHODS The Shrewsbury Splenic Flexure Siting (SSFS) system involves siting of the splenic flexure using the vertebral level (VL) as a reference point. We asked three surgical registrars (SRs) to analyse 20 CT scans of patients undergoing colonic resection to ascertain the anatomical site of the splenic flexure using the SSFS system. The distance from the centre of the vertebral body to the lateral edge (CVBL) of the splenic flexure was measured, as was the distance from the centre of the vertebral body to the inner abdominal wall (CVBI) along the same line, on axial images. RESULTS VL assessment demonstrated substantial inter-observer agreement with a kappa (kappa) value of 0.742 (95% confidence interval (CI), 0.463-0.890). CVBL and CVBI demonstrated very strong inter-observer agreement (CVBL: kappa = 0.905 (95% CI, 0.785-0.961); CVBI: 0.951 (0.890-0.979) (p<0.001). Overall, there was strong correlation between assessments by all three SRs across the three variables measured. CONCLUSIONS The SSFS system is an accurate method to site the splenic flexure anatomically using CT. We can use the SSFS system to develop a validated scoring system to help colorectal surgeons assess the difficulty of SFM. PMID- 27659371 TI - Data protection: in our patients' hands. PMID- 27659372 TI - A decade of major vascular trauma: Lessons learned from gang and civilian warfare. AB - INTRODUCTION Trinidad and Tobago is a trans-shipment point for the illegal trade of drugs, arms and ammunition and, as such, has a high incidence of gang-related warfare and drug-related crimes. This has led to a high incidence of gunshot and stab wounds, with associated major vascular injuries. We describe our management strategies learned from a decade of vascular trauma experience. METHODS A retrospective analysis of age, gender, type of trauma, vessel injured, procedure and outcome for all cases of vascular trauma between 2006 and 2015 at two surgical units in Trinidad and Tobago. RESULTS There were 198 vascular trauma cases (232 procedures), involving 159 (80%) males at a mean age of 33 years. Gunshots accounted for 103 (52%) cases, followed by stabs/chops (n=50; 25%) and lacerations (n=15; 8%). The most commonly injured vessels were the radial/ulnar arteries (n=39; 20%) and the superficial femoral artery (n=37; 19%). There were seven pseudoaneurysms and three traumatic arteriovenous fistulae. Repair techniques included primary (n=82; 35%), reversed vein (n=63; 27%), polytetrafluoroethylene (n=58; 25%), oversew (n=24; 10%) and endovascular (n=5; 2%) techniques. There were eight (4%) secondary amputations and eight (4%) deaths. CONCLUSIONS Major vascular trauma causes significant morbidity and mortality in Trinidad and Tobago, with the majority of cases due to gunshot injuries secondary to gang-related warfare and civilian violence. We compare our experience with that in the literature on the epidemiology and management of vascular trauma. PMID- 27659373 TI - Complications of biliary-enteric anastomoses. AB - INTRODUCTION Biliary-enteric anastomoses are performed for a range of indications and may result in early and late complications. The aim of this study was to assess the risk factors and management of anastomotic leak and stricture following biliary-enteric anastomosis. METHODS A retrospective analysis of the medical records of patients who underwent biliary-enteric anastomoses in a tertiary referral centre between 2000 and 2010 was performed. RESULTS Four hundred and sixty-two biliary-enteric anastomoses were performed. Of these, 347 (75%) were performed for malignant disease. Roux-en-Y hepaticojejunostomy or choledocho-jejunostomy were performed in 440 (95%) patients. Perioperative 30-day mortality was 6.5% (n=30). Seventeen patients had early bile leaks (3.7%) and 17 had late strictures (3.7%) at a median of 12 months. On univariable logistic regression analysis, younger age was a significant risk factor for biliary anastomotic leak. However, on multivariable analysis only biliary reconstruction following biliary injury (odds ratio [OR]=6.84; p=0.002) and anastomosis above the biliary confluence (OR=4.62; p=0.03) were significant. Younger age and biliary reconstruction following injury appeared to be significant risk factors for biliary strictures but multivariable analysis showed that only younger age was significant. CONCLUSIONS Biliary-enteric anastomoses have a low incidence of early and late complications. Biliary reconstruction following injury and a high anastomosis (above the confluence) are significant risk factors for anastomotic leak. Younger patients are significantly more likely to develop an anastomotic stricture over the longer term. PMID- 27659374 TI - Inpatient magnetic resonance cholangiopancreatography: does it increase the efficiency in emergency hepatopancreaticobiliary surgery services? AB - INTRODUCTION Magnetic resonance cholangiopancreatography (MRCP) is commonly used to evaluate the biliary tree, although indications for patients who require inpatient imaging are not fully defined. The aim of this study was to evaluate inpatient MRCP performed on surgical patients and to devise a treatment pathway for these patients. MATERIAL AND METHODS All adult inpatient MRCP examinations between January 2012 and December 2013 were reviewed. Demographic, clinical and radiological data were collated. RESULTS During the study period, 271 inpatient MRCP were requested, of which 234 examinations were included. The majority of patients were female (n=140) and the median age was 63 years (range 16-93 years). Surgical admissions accounted for 171 (73%) of cases. Indications for inpatient MRCP include gallstone-related complications (n=173; 74%), malignant process (n=17; 7%) and other indications (n=44; 19%). Overall, inpatient MRCP led to further inpatient interventions in 22% (gallstone group, n=32, 18%; patients with malignancy, n=8, 47%; other indications, n=12, 27%). The median duration of inpatient MRCP from request to examination was 2 days (range 0-15 days) and median reporting after examination was 1 day (range 0-14 days). DISCUSSION AND CONCLUSION Improved access and timely reporting of iMRCP may reduce length of hospital stay. Inpatient MRCP also led to further inpatient interventions, in particular, in patients with malignancy. PMID- 27659375 TI - ParietexTM Composite mesh versus DynaMesh(r)-IPOM for laparoscopic incisional and ventral hernia repair: a retrospective cohort study. AB - INTRODUCTION Laparoscopic incisional and ventral hernia repair (LIVHR) is widely accepted and safe but the type of mesh used is still debated. We retrospectively compared postoperative outcomes with two different meshes commonly used in LIVHR. METHODS This is a retrospective study of patients who underwent incisional hernia repair between January 2008 and December 2010. Two meshes were used: ParietexTM Composite (Covidien, New Haven, CT, USA) and the DynaMesh(r)-IPOM (FEG Textiltechnik mbH, Aachen, Germany). The two groups were compared with respect to recurrence rates, incidence of seroma and intestinal obstruction. RESULTS Among the 88 patients who underwent LIVHR, 75 patients (85.2%) presented with primary incisional hernia, 10 (11.4%) presented with a first recurrence and 3 (3.4%) presented with a second recurrence. Median follow-up was 53.6 months (range 40-61 months). 12.9% of patients had recurrence in the ParietexTM Composite mesh group (n=62) in comparison to 3.8% in the DynaMesh(r)-IPOM mesh group (n=26; P=0.20). DynaMesh(r)-IPOM was associated with a significantly higher incidence of intestinal obstruction secondary to adhesions (11.5% vs. 0%, P=0.006) and lower incidence of seroma and haematoma formation compared to ParietexTM composite mesh group (0% vs. 6.4% of patients; P=0.185). CONCLUSIONS LIVHR is a safe and feasible technique. Dynamesh(r)-IPOM is associated with a significantly higher incidence of adhesion related bowel obstruction, albeit with a lower incidence of recurrence, seroma and haematoma formation compared with ParietexTM Composite mesh. However, there is a need for further well-designed, multicentre randomised controlled studies to investigate the use of these meshes. PMID- 27659376 TI - Encountering a high jugular bulb during ear surgery. AB - Encounters with jugular bulb abnormalities during ear surgery are a rare but recognised problem. A high riding jugular bulb is present in 10%-15% of patients and its variable position within the temporal bone can lead to problems as brisk venous haemorrhage can result if the bulb is inadvertently opened. The case of a 52-year-old woman with a central tympanic membrane perforation who underwent elective endaural myringoplasty and experienced brisk bleeding on raising the tympanomeatal flap is presented. PMID- 27659377 TI - Paraneoplastic polymyositis presenting as a clinically occult breast cancer. AB - Paraneoplastic syndrome affects less than 1% of cancer patients. Diagnosis of paraneoplastic syndrome with neurological presentation requires screening for an underlying malignancy, including a complete history, physical examination and imaging studies. Treatment often results in symptom stability, rather than improvement. Paraneoplastic polymyositis can precede or instantaneously occur at diagnosis or treatment of a primary tumour, while neurological symptoms can persist even following cancer treatment. We report a rare case of metaplastic breast carcinoma with an unusual presentation of paraneoplastic polymyositis. PMID- 27659379 TI - A rare case of peripheral vascular graft infection by Aspergillus fumigatus and review of the literature. AB - We present an unusual case of a 74-year-old woman who presented with a pseudoaneurysm at the site of a previous prosthetic femoro-popliteal bypass graft and underwent an urgent repair with pseudoaneurysm excision and extra-anatomic placement of an autologous venous graft. Microbiology examination revealed Aspergillus fumigatus infection of the graft, which is a very rare condition. Long-term antifungal medication has been administrated with positive outcome. Only a few cases have been reported in literature, mainly involving aortic grafts. Most patients are immunocompetent and with late presentation. Successful outcome can only be achieved with long-term antifungal treatment and extra anatomic replacement of the graft. PMID- 27659378 TI - Spontaneous diaphragmatic rupture following robotic prostatectomy. AB - Robotic surgery is an established therapy for localised prostate cancer and is replacing conventional laparoscopic prostatectomy in developed countries. Port site hernia is a recognised, albeit small, risk following laparoscopic or robotic surgery. We report a case of spontaneous rupture of the right hemidiaphragm following robotic prostatectomy. PMID- 27659380 TI - A case of endobronchial paraganglioma. AB - Paragangliomas are rare lung tumours; endobronchial localisation is even more rare. This report describes the case of a 59-year-old patient with a symptomatic endobronchial paraganglioma successfully resected by means of pulmonary lobectomy. Recognition of this uncommon tumour can lead to a correct diagnosis and therapeutic strategy. PMID- 27659381 TI - A rare case of a direct ocular contact burn to the right eye. AB - Ocular thermal burns represent an oculoplastic emergency, with the potential for blindness owing to limbal ischaemia. We present a rare case of a 66-year-old man who sustained a direct thermal contact burn to the right eye. PMID- 27659382 TI - Delayed diagnosis of central skull-base osteomyelitis with abscess: case report and learning points. AB - Central skull-base osteomyelitis (CSBO) is a rare life-threatening infection, usually resulting from medial spread of necrotising otitis externa. Here, we describe a case with no identifiable source of infection, causing a delay in diagnosis. An 80-year-old man with Crohn's disease treated with mesalazine presented with collapse and tonic-clonic seizure. Computed tomography and magnetic resonance imaging showed a nasopharyngeal mass that was initially thought to be a neoplasm. Awaiting formal biopsy, he represented with collapse and repeat imaging showed features of abscess formation. Review of previous scans revealed skull-base erosion and the diagnosis was revised to skull-base osteomyelitis. This is the first reported case of CSBO associated with mesalazine use, an aminosalicylate used in Crohn's disease. It is only the second reported case with abscess formation. We discuss the learning points in making a timely diagnosis and examine the potential association of factors such as mesalazine use and abscess formation in this case. PMID- 27659383 TI - Unusual variant of inverted Y ureteral duplication with an ipsilateral seminal vesicle cyst and renal dysgenesis. AB - Inverted Y malformation is a rare variant of ureteral duplication with a marked female predominance. We describe a case of inverted Y ureteral duplication with concurrent ectopic ureteral insertion into a seminal vesicle cyst, a ureterocoele and renal dysgenesis, which occurred in a 29-year-old man with lower urinary tract symptoms, haematospermia and postcoital discomfort. To our knowledge, this is the first reported case with this constellation of urogenital abnormalities. PMID- 27659384 TI - Galactorrhoea of the neck following pectoralis major reconstruction of a pharyngeal defect. AB - We describe a case of postoperative galactorrhea following the use of a pedicled pectoralis major myocutaneous flap for reconstruction of a pharyngolaryngeal defect in a woman with squamous cell carcinoma. We believe this to be unique in the literature, and an important complication to be reported, due to the similarities in appearance of galactorrhoea and postoperative aerodigestive tract/cutaneous fistula. PMID- 27659385 TI - Structure of the second Single Stranded DNA Binding protein (SSBb) from Mycobacterium smegmatis. AB - All mycobacteria with sequenced genomes, except M. leprae, have a second Single Stranded DNA Binding protein (SSBb) in addition to the canonical one (SSBa). This paralogue from M. smegmatis (MsSSBb) has been cloned, expressed and purified. The protein, which is probably involved in stress response, has been crystallized and X-ray analyzed in the first structure elucidation of a mycobacterial SSBb. In spite of the low sequence identity between SSBas and SSBbs in mycobacteria, the tertiary and quaternary structure of the DNA binding domain of MsSSBb is similar to that observed in mycobacterial SSBas. In particular, the quaternary structure is 'clamped' using a C-terminal stretch of the N-domain, which endows the tetrameric molecule with additional stability and its characteristic shape. Comparison involving available, rather limited, structural data on SSBbs from other sources, appears to suggest that SSBbs could exhibit higher structural variability than SSBas do. PMID- 27659387 TI - [Nevus comedonicus: Somatic mutations in NEK9]. PMID- 27659386 TI - [The role of reflectance confocal microscopy in the diagnosis of ocular-cutaneous erucism or dermatitis and keratitis induced by pine processionary caterpillar hairs]. PMID- 27659388 TI - [CONDYDAV: A multicentre observational study of patients presenting external genital warts in France]. AB - BACKGROUND: Since 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear. OBJECTIVES: To determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination. PATIENTS AND METHODS: In this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France. RESULTS: A total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil(r) and one with Cervarix(r). Cryotherapy was the preferred treatment. CONCLUSION: With the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented. PMID- 27659389 TI - Effects of Treating Primary Aldosteronism on Renal Function. AB - Longstanding primary aldosteronism (PA) has deleterious effects on renal function, often masked until treatment (adrenalectomy or spironolactone) is initiated. It has been suggested that PA causes relative glomerular hyperfiltration, explaining the decline in estimated glomerular filtration rate (eGFR) after treatment. In this retrospective study, the authors retrieved the clinical characteristics and eGFR of 134 PA patients before and 6 months after treatment. Using multiple regression analysis, the predictors for eGFR decline and the predictors of ultimately attained renal function in 113 patients was assessed. eGFR declined by 15.3+/-14.2 (range 19-63) mL/min, independent predictors were pretreatment plasma aldosterone, eGFR, plasma renin, and plasma potassium. Independent predictors of ultimately attained eGFR after treatment were pretreatment plasma aldosterone, age, eGFR, and plasma potassium. Our findings lend support to the hypothesis that higher aldosterone levels cause relative glomerular hyperfiltration. The severity of pretreatment aldosterone excess is the most important risk factor for renal function decline. PMID- 27659390 TI - Chemical constituents from Cordia alliodora and C. colloccoca (Boraginaceae) and their biological activities. AB - Two new natural products, 5-O-[beta-D-apiofuranosyl-(1->6)-beta-d-glucopyranosyl] 1-isoindolinone (1) as well as N-(2E)-3-[(2S,3R)-2-(4-hydroxy-3-methoxyphenyl)-3 (hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]acryloylglycine (2), along with four known compounds (3-6), were isolated from the methanolic extract of Cordia alliodora root bark. Furthermore, the methanolic extract of Cordia colloccoca leaves, afforded the known flavonoids afzelin (7) and quercitrin (8). The isolated secondary metabolites were assayed for their antimicrobial activities against a panel of 6g positive and negative bacteria and three human pathogenic fungi. Moreover, their antiproliferative effect was also evaluated in vitro against the human non-small-cell bronchopulmonary carcinoma line NSCLC-N6, the epidermoid lung cancer cell line A549 as well as the normal human skin fibroblast cell line (AG01523). PMID- 27659391 TI - Comparing healthcare utilization among health survey respondents with the total population - are respondents representative? AB - BACKGROUND: Surveys are often used for analysis of health status and healthcare utilization in different socioeconomic groups. However, differential non-response rates may bias results. The aim of this study was to compare register data on outpatient healthcare utilization among respondents to a health survey to that of the total population and to investigate whether socioeconomic differences in outpatient healthcare utilization differ between survey respondents and the total population. METHOD: Data from the Stockholm Public Health Survey 2010 (n = 30,767 aged 18 + years) were linked to register data on outpatient healthcare utilization in order to investigate differentials by socioeconomic groups, country of birth and residential areas among respondents, using logistic regression and negative binomial regression. These results were compared to analyses of register data on outpatient healthcare utilization for the total population (n = 1.6 million aged 18 + years) of Stockholm County. RESULTS: Outpatient healthcare utilization was generally higher among survey respondents than in the total population, especially among men. The proportion of individuals having made at least one visit was significantly higher among survey respondents than in the total population but the differences were smaller regarding the average number of visits. Socioeconomic differences in outpatient healthcare utilization between subgroups were largely similar among survey respondents and in the total population. However, individuals born outside Sweden responding to the survey had significantly higher outpatient healthcare utilisation than individuals born outside Sweden in the total population. CONCLUSION: Compared to the total population, a greater proportion of survey respondents had made at least one outpatient visit to the doctor. However, the mean number of registered visits did not differ significantly between survey respondents and the total population. Hence, depending on the outcome measure used survey-based estimates may result in slightly biased prevalence estimates, however, relative differences among survey respondents were to a large degree comparable to relative differences in the total population. In contrast, survey respondents born outside Sweden differed from persons born outside Sweden in the total population to a degree where they may not be representative and comparisons between this group and other subgroups, using survey data, may be biased. PMID- 27659393 TI - Optimal Cutoff Scores for Alzheimer's Disease Using the Chinese Version of Mini Mental State Examination Among Chinese Population Living in Rural Areas. AB - To explore the optimal cutoff score for initial detection of Alzheimer's Disease (AD) through the Chinese version of Mini-Mental State Examination (CMMSE) in rural areas in China, we conducted a cross-sectional study within the Linxian General Population Nutritional Follow-up study. 16,488 eligible cohort members participated in the survey and 881 completed the CMMSE. Among 881 participants, the median age (Interquartile range) was 69.00 (10.00), 634 (71.92%) were female, 657 (74.57%) were illiterate, 35 (3.97%) had 6 years of education or higher, and 295 (33.48%) were diagnosed with AD. By reducing the CMMSE criteria for illiterate to 16 points, primary school to 19 points, and middle school or higher to 23 points, the efficiency of Chinese version of Mini-Mental State Examination can be significantly improved for initial detection of AD in rural areas in China, especially in those nutrition deficient areas. PMID- 27659392 TI - An Education Intervention to Enhance Staff Self-Efficacy to Provide Dementia Care in an Acute Care Hospital in Canada: A Nonrandomized Controlled Study. AB - Education is needed for enhanced capacity of acute hospitals to provide dementia care. A nonrandomized controlled, repeated-measures design was used to evaluate a dementia education program delivered to an intervention group (IG, n = 468), compared to a wait-listed group (n = 277), representing separate sites of a multisite hospital. Participants completed self-efficacy for dementia and satisfaction measures and provided written descriptions of dementia care collected at baseline, postintervention (IG only), and at 8-week follow-up. Oral narratives were gathered from IG participants 8 weeks postintervention. The IG demonstrated significant improvement in self-efficacy scores from baseline to immediately postintervention (P < .001), sustained at 8 weeks. There were no changes from baseline to 8 weeks postintervention evident in the wait-listed group (P = .21). Intervention group participants described positive impacts including implementation of person-centered care approaches. Implementation of dementia care education programs throughout hospital settings is promising for the enhancement of dementia care. PMID- 27659394 TI - Efficacy of Hybrid Plasma Scalpel in Reducing Blood Loss and Transfusions in Direct Anterior Total Hip Arthroplasty. AB - BACKGROUND: Allogeneic blood transfusions have inherent risk and direct cost in total hip arthroplasty. Anterior total hip arthroplasty has grown in popularity with increased utilization. This approach may offer an enhanced recovery but has been associated with increased blood loss. Several technologies have been developed including the Canady Hybrid Plasma Scalpel (CHPS) and Aquamantys Bipolar Sealer (BS) to decrease blood loss. METHODS: Two hundred forty-four consecutive patients undergoing anterior supine intermuscular total hip arthroplasty were separated by intraoperative cautery device (CHPS vs BS). Exclusion criteria included blood dyscrasias and contraindication to tranexamic acid. Demographic data, blood loss, transfusion requirements, and Harris Hip Scores were obtained. Differences between groups were evaluated using the Student t-test or Wilcoxon rank-sum test for continuous variables and chi-square test for categorical variables. RESULTS: There were no differences in demographic data between the groups. Patients in the CHPS group had a significantly smaller decrease in postoperative hemoglobin (-2.3 mg/dL vs -2.7 mg/dL, P < .05), estimated blood loss (240.3 mL vs 384.4 mL, P < .001), and calculated actual blood loss (1.11 L vs 2.47 L, P < .001). There were 12 transfusions in the BS group and none in CHPS group (P < .001). CONCLUSION: The use of the hybrid plasma scalpel resulted in significantly less blood loss and transfusions than the BS. Additionally, patients treated with the hybrid plasma scalpel had significantly shorter operative times and reduced hospital length of stay. The hybrid scalpel shows promise in reducing blood loss in anterior total hip arthroplasty and is a valuable tool in the multimodal approach to avoiding transfusions. PMID- 27659395 TI - Referral Bias in Primary Total Knee Arthroplasty: Retrospective Analysis of 22,614 Surgeries in a Tertiary Referral Center. AB - BACKGROUND: Patients who travel a significant distance to obtain surgical treatment typically experience better outcomes. This is called the referral bias and can limit the generalizability of studies performed at large tertiary care centers. We explored the influence of referral bias by comparing the clinical characteristics and outcomes of total knee arthroplasty (TKA) at a large tertiary care hospital in the United States. METHODS: The study cohort included 22,614 primary TKA procedures performed between 1985 and 2010. Patients were stratified into 5 groups using home address zip codes and according to travel distance from the hospital. Clinical characteristics and the risk of TKA complications and surgical outcomes (instability, surgical-site infections, and thrombovascular complications within the first year, reoperations, revisions, and mortality) were compared across the 5 groups. RESULTS: Compared with local patients, patients who traveled from other parts of the United States were significantly younger (mean age 67.8 vs 68.5 years; P < .05), were more likely to be male (47% vs 38%, P < .001), had lower body mass index (mean 30.4 vs 31.8 kg/m2; P < .001), were more likely to have inflammatory arthritis or neoplasms as surgical indications (P < .05), and were more likely to have a history of prior surgeries on the same knee (20% vs 14%; P < .001). Referral patients also had significantly higher American Society of Anesthesiologists scores and longer operative times (mean 173 vs 156 minutes P < .001). Despite these differences, the risk of instability, surgical site infections, thrombovascular complications, reoperations, and revision surgeries were similar across the 5 groups. CONCLUSION: Although referral patients differ from local patients, the groups seem to experience largely similar complication and revision rates after TKA. PMID- 27659396 TI - The Direct Anterior Approach for Hip Revision: Accessing the Entire Femoral Diaphysis Without Endangering the Nerve Supply. AB - BACKGROUND: The direct anterior approach (DAA) to the hip has been criticized as an approach that is limited to primary arthroplasty only. Our study objective was to demonstrate, in a cadaveric setting, that an alternate extension of the DAA can be used to reach the femur at the posterior border of the lateral vastus muscle without endangering the nerve supply. METHODS: The iliotibial tract is split anteriorly and pulled laterally, thereby opening the interval to the lateral-posterior aspect of the vastus muscle. The muscle fascia is incised at the posterior border to access the femoral diaphysis. The vastus mobilization is started distally and laterally to the greater trochanter, leaving a muscular bridge between the vastus and the medial gluteal muscle intact. If it is necessary to open the femoral cavity for implant retrieval, we perform an anterior wall osteotomy instead of an extended trochanteric osteotomy. RESULTS: It was possible to split the iliotibial band and pull it laterally, thereby exposing the entire vastus lateralis muscle. The junction of the vastus lateralis and vastus intermedius was not encountered in all cases, nor was the nerve supply with all nerve fibers in that interval. CONCLUSION: The alternate technique described here for accessing the femoral diaphysis allows for easy access to the lateral aspect of the vastus lateralis and the femoral diaphysis. Using this technique, it should also be possible to access the femur and perform all necessary reconstructive procedures on it without damaging the surrounding nerve structures. PMID- 27659397 TI - An Assessment of Gender-Specific Risk of Implant Revision After Primary Total Hip Arthroplasty: A Systematic Review and Meta-analysis. AB - BACKGROUND: Total hip arthroplasty (THA) has been a successful reconstructive procedure to mitigate pain associated with diseases of the hip joint. However, some THA procedures require revision due to mechanical or biological failure. The purpose of this study was to synthesize and examine the evidence on the relative risk of revision in men and women after primary THA procedures. METHODS: We conducted a systematic literature review of cohort studies reporting THA revision risk estimate by gender. Study quality scoring and a random effects meta-analysis were performed to estimate the meta-relative risk (meta-RR) and corresponding 95% confidence interval (95% CI) of revision, comparing men to women. RESULTS: Males had a statistically significant increased risk of revision after primary THA (meta-RR = 1.33 [95% CI: 1.13-1.57]), when compared to females. When stratified by cause of revision, males had a statistically significant increased risk of revision due to any cause (meta-RR = 1.16 [95% CI: 1.01-1.33]), aseptic loosening (meta-RR = 1.54 [95% CI: 1.05-2.25]), and infection (meta-RR = 1.55 [95% CI: 1.11 2.15]). For primary THA operations performed during the 2000s, males in Europe had a statistically significant increased risk of revision (meta-RR 1.42 [95% CI: 1.25-1.61]) while males in the United States had a statistically significant decreased risk of revision (meta-RR 0.80 [95% CI: 0.72-0.89]). CONCLUSION: These results provide evidence for an increased risk of revision after THA among males, which may be impacted by geographic location and time period of operation. Findings suggest that a better understanding of the underlying drivers of gender specific risks would help reduce postsurgery complications. PMID- 27659398 TI - New insights into the interaction between pyrrolyl diketoacids and HIV-1 integrase active site and comparison with RNase H. AB - HIV-1 integrase (IN) inhibitors are one of the most recent innovations in the treatment of HIV infection. The selection of drug resistance viral strains is however a still open issue requiring constant efforts to identify new anti-HIV-1 drugs. Pyrrolyl diketo acid (DKA) derivatives inhibit HIV-1 replication by interacting with the Mg2+ cofactors within the HIV-1 IN active site or within the HIV-1 reverse-transcriptase associated ribonuclease H (RNase H) active site. While the interaction mode of pyrrolyl DKAs with the RNase H active site has been recently reported and substantiated by mutagenesis experiments, their interaction within the IN active site still lacks a detailed understanding. In this study, we investigated the binding mode of four pyrrolyl DKAs to the HIV-1 IN active site by molecular modeling coupled with site-directed mutagenesis studies showing that the DKA pyrrolyl scaffold primarily interacts with the IN amino residues P145, Q146 and Q148. Importantly, the tested DKAs demonstrated good effectiveness against HIV-1 Raltegravir resistant Y143A and N155H INs, thus showing an interaction pattern with relevant differences if compared with the first generation IN inhibitors. These data provide precious insights for the design of new HIV inhibitors active on clinically selected Raltegravir resistant variants. Furthermore, this study provides new structural information to modulate IN and RNase H inhibitory activities for development of dual-acting anti-HIV agents. PMID- 27659399 TI - Adrenergic signaling elements in the bladder wall of the adult rat. AB - A growing body of work is describing the absence of a significant sympathetic innervation of the detrusor implying little sympathetic regulation of bladder contractility. However, low doses of adrenergic agonists are capable of relaxing the bladder smooth muscle. If these effects underpin a physiological response then the cellular nature and operation of this system are currently unknown. The present immunohistochemistry study was done to explore the existence of alternative adrenergic signaling elements in the rat bladder wall. Using antibodies to tyrosine hydroxylase (TH) and vesicular mono-amine transporter (vmat), few adrenergic nerves were found in the detrusor although TH immunoreactive (IR) nerves were apparent in the bladder neck. TH-IR and vmat-IR nerves were however abundant surrounding blood vessels. A population of vmat-IR cells was found within the network of interstitial cells that surround the detrusor muscle bundles. These vmat-IR cells were not or only weakly TH-IR. This suggests that these interstitial cells have the capacity to store and release catecholamines that may involve noradrenaline. Cells expressing the beta1 adrenoceptor (beta1AR-IR) were also detected within the interstitial cell network. Double staining with antibodies to beta1AR and vmat suggests that the majority of vmat-IR interstitial cells show beta1AR-IR indicative of an autocrine signaling system. In conclusion, a population of interstitial cells has the machinery to store, release and respond to catecholamines. Thus, there might exist a non-neuronal beta-adrenergic system operating in the bladder wall possibly linked to one component of motor activity, micro-contractions, a system that may be involved in mechanisms underpinning bladder sensation. PMID- 27659400 TI - [Is there workplace violence in the Spanish nursing homes?] PMID- 27659401 TI - Hyperferritinemia increases the risk of hyperuricemia in HFE-hereditary hemochromatosis. AB - OBJECTIVES: Hyperuricemia is becoming increasingly frequent in the population, and is known to be sometimes the cause of gout. The impact of uric acid is still not clearly understood, however. The iron metabolism may interact with the uric acid metabolism. The aim of this study was to examine the relationship between the serum uric acid and serum ferritin levels in a cohort of hemochromatosis patients who were homozygous for the HFE p.Cys282Tyr mutation. METHODS: 738 patients with the HFE gene mutation Cys282Tyr in the homozygous state were included in the study. The variables measured during the initial evaluation were compared in univariate analysis by Student's t test. In multivariate analysis, linear stepwise regression was used. RESULTS: In the group of hyperuricemic patients, ferritinemia was significantly higher than in the group of non hyperuricemic patients (1576.7+/-1387.4MUg/l vs. 1095.63+/-1319.24MUg/l, P<0.005). With multivariate analysis, only ferritin and BMI independently explained the uricemia (R2=0.258) after adjustment for age, glycemia and CRP. The correlation between uricemia and log(ferritin) with partial regression correlation coefficients was 0.307 (P<0.01). CONCLUSIONS: The increase in uricemia is associated with the increase in ferritin in a population of patients who were homozygous for the HFE gene mutation p.Cys282Tyr and this independently of factors commonly associated with hyperuricemia. The increase in uric acid associated with hyperferritinemia, could be a response to the visceral toxicity of excess non-transferrin bound iron linked to oxidative stress via the antioxidant properties of uric acid. PMID- 27659402 TI - Serum procalcitonin measurement is not a useful biomarker in the detection of primary infectious spondylodiscitis. PMID- 27659403 TI - Alarmins firing arthritis: Helpful diagnostic tools and promising therapeutic targets. AB - Alarmins are endogenous molecules with homeostatic roles that have reached the focus of research in inflammatory arthritis in the last two decades, mostly due to their ability to indicate tissue related damage after active or passive release from injured cells. From HMGB1, S100A8/A9 and S100A12 proteins, over heat shock proteins (HSPs) and purine metabolites (e.g. uric acid, ATP) to altered matrix proteins and interleukin-33 (IL-33), a number of alarmins have been determined until now as having a role in rheumatoid arthritis, psoriatic and juvenile idiopathic arthritis, as well as spondyloarthritis and gout. Although formerly being linked to initiation and chronification of inflammatory arthritis, driving auto- and paracrine inflammatory loops, more recent research has also unraveled the alarmins' role in the crosstalk between innate and adaptive immunity and in resolution of inflammation. Providing a state-of-the-art overview of known alarmins, this review lists the known modes of action and pathologic contribution of alarmins to inflammatory arthritis, as well as biomarker potential of alarmins in the clinical setting for tracking disease severity. Based upon research on animal experimental models (CIA, AIA) and clinical trials, a look is made into potentially viable strategies for modifying alarmin secretion and their target receptor (e.g. TLR, RAGE) interaction with the purpose of attenuating arthritic disease. PMID- 27659404 TI - Pulmonary embolism induced by methotrexate in a dermatomyositis patient. PMID- 27659405 TI - Cystic lung disease in Sjogren's syndrome: An observational study. AB - OBJECTIVES: To analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjogren's syndrome (SS). METHODS: From June 2010 to February 2015, 90 consecutive SS patients [60.1+/-14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records. RESULTS: Twenty-one (23.3%) patients had cysts on CT scan performed 40.5+/-54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3+/ 15.3 versus 58.5+/-14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1+/ 17.7months), no patient developed specific lung disease or lymphoproliferative disorders. CONCLUSIONS: Cystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS. PMID- 27659406 TI - Assessment of children's nutritional attitudes before oral food challenges to identify patients at risk of food reintroduction failure: a prospective study. AB - BACKGROUND: Inappropriate dietary eliminations may impair quality of life, affect children's growth and unnecessarily impact on healthcare costs. Previous retrospective studies reported that around 25% of children continue a food avoidance diet despite a negative oral food challenge (OFC). A definite pattern has not been found yet for patients not reintroducing the food. This study aimed to examine the role of child's nutritional attitudes and maternal anxiety in reintroducing food after a negative OFC. METHODS: A prospective study was conducted involving 81 mothers of children with IgE-mediated food allergy. They completed a survey on nutritional behaviour and attitudes and the State-Trait Anxiety Inventory on the day of OFC and 6 months later. RESULTS: In total, 11.1% of children never or rarely ate the food after a negative OFC. Consumption of the reintroduced food is positively correlated to child's interest in tasting new foods before and after OFC and to changes in child's nutritional habits after OFC. It is negatively correlated to monotony of the diet after OFC. No correlations were found with other participants' characteristics or maternal anxiety. State anxiety significantly decreased after the OFC. A correlation was found between trait and state anxiety and the degree of change in nutritional habits after OFC. CONCLUSIONS: Evaluating child's approach towards food before the OFC is a promising approach to identify patients at risk of food reintroduction failure. Furthermore, it underlined the importance of reassessing food consumption in all patients after a negative OFC and supporting patients in the reintroduction of food. PMID- 27659407 TI - Combined Analysis of Three Large Interventional Trials With Gliptins Indicates Increased Incidence of Acute Pancreatitis in Patients With Type 2 Diabetes. AB - OBJECTIVE: Data on the possible relationship of gliptin treatment with the incidence of acute pancreatitis have been controversial. The aim of the current study was to combine data on the incidence of acute pancreatitis from three large randomized controlled trials. RESEARCH DESIGN AND METHODS: Three trials designed to test cardiovascular safety and efficacy of add-on treatment with a gliptin were included in the analysis, as follows: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin). The trials included 18,238 gliptin-treated patients and 18,157 placebo-treated patients. Data were combined using a random effects model meta-analysis. RESULTS: The incidence of acute pancreatitis was significantly increased in the gliptin-treated patients when compared with the control groups (odds ratio 1.79 [95% CI 1.13-2.82], P = 0.013). The difference in the absolute risk was small (0.13%). CONCLUSIONS: Treatment with gliptins significantly increased the risk for acute pancreatitis in a combined analysis of three large controlled randomized trials. PMID- 27659409 TI - Sarcolemmal alpha2-adrenoceptors control protective cardiomyocyte-delimited sympathoadrenal response. AB - Sustained cardiac adrenergic stimulation has been implicated in the development of heart failure and ventricular dysrhythmia. Conventionally, alpha2 adrenoceptors (alpha2-AR) have been assigned to a sympathetic short-loop feedback aimed at attenuating catecholamine release. We have recently revealed the expression of alpha2-AR in the sarcolemma of cardiomyocytes and identified the ability of alpha2-AR signaling to suppress spontaneous Ca2+ transients through nitric oxide (NO) dependent pathways. Herein, patch-clamp measurements and serine/threonine phosphatase assay revealed that, in isolated rat cardiomyocytes, activation of alpha2-AR suppressed L-type Ca2+ current (ICaL) via stimulation of NO synthesis and protein kinase G- (PKG) dependent activation of phosphatase reactions, counteracting isoproterenol-induced beta-adrenergic activation. Under stimulation with norepinephrine (NE), an agonist of beta- and alpha adrenoceptors, the alpha2-AR antagonist yohimbine substantially elevated ICaL at NE levels >10nM. Concomitantly, yohimbine potentiated triggered intracellular Ca2+ dynamics and contractility of cardiac papillary muscles. Therefore, in addition to the alpha2-AR-mediated feedback suppression of sympathetic and adrenal catecholamine release, alpha2-AR in cardiomyocytes can govern a previously unrecognized local cardiomyocyte-delimited stress-reactive signaling pathway. We suggest that such aberrant alpha2-AR signaling may contribute to the development of cardiomyopathy under sustained sympathetic drive. Indeed, in cardiomyocytes of spontaneously hypertensive rats (SHR), an established model of cardiac hypertrophy, alpha2-AR signaling was dramatically reduced despite increased alpha2-AR mRNA levels compared to normal cardiomyocytes. Thus, targeting alpha2-AR signaling mechanisms in cardiomyocytes may find implications in medical strategies against maladaptive cardiac remodeling associated with chronic sympathoadrenal stimulation. PMID- 27659408 TI - Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013. AB - OBJECTIVE: To examine temporal trends in utilization of glucose-lowering medications, glycemic control, and rate of severe hypoglycemia among patients with type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS: Using claims data from 1.66 million privately insured and Medicare Advantage patients with T2DM from 2006 to 2013, we estimated the annual 1) age- and sex-standardized proportion of patients who filled each class of agents; 2) age-, sex-, race-, and region standardized proportion with hemoglobin A1c (HbA1c) <6%, 6 to <7%, 7 to <8%, 8 to <9%, >=9%; and 3) age- and sex-standardized rate of severe hypoglycemia among those using medications. Proportions were calculated overall and stratified by age-group (18-44, 45-64, 65-74, and >=75 years) and number of chronic comorbidities (zero, one, and two or more). RESULTS: From 2006 to 2013, use increased for metformin (from 47.6 to 53.5%), dipeptidyl peptidase 4 inhibitors (0.5 to 14.9%), and insulin (17.1 to 23.0%) but declined for sulfonylureas (38.8 to 30.8%) and thiazolidinediones (28.5 to 5.6%; all P < 0.001). The proportion of patients with HbA1c <7% declined (from 56.4 to 54.2%; P < 0.001) and with HbA1c >=9% increased (9.9 to 12.2%; P < 0.001). Glycemic control varied by age and was poor among 23.3% of the youngest and 6.3% of the oldest patients in 2013. The overall rate of severe hypoglycemia remained the same (1.3 per 100 person-years; P = 0.72), declined modestly among the oldest patients (from 2.9 to 2.3; P < 0.001), and remained high among those with two or more comorbidities (3.2 to 3.5; P = 0.36). CONCLUSIONS: During the recent 8-year period, the use of glucose lowering drugs has changed dramatically among patients with T2DM. Overall glycemic control has not improved and remains poor among nearly a quarter of the youngest patients. The overall rate of severe hypoglycemia remains largely unchanged. PMID- 27659410 TI - Enantioselective cascade biocatalysis for deracemization of 2-hydroxy acids using a three-enzyme system. AB - BACKGROUND: Enantiopure 2-hydroxy acids are key intermediates for the synthesis of pharmaceuticals and fine chemicals. We present an enantioselective cascade biocatalysis using recombinant microbial cells for deracemization of racemic 2 hydroxy acids that allows for efficient production of enantiopure 2-hydroxy acids. RESULTS: The method was realized by a single recombinant Escherichia coli strain coexpressing three enzymes: (S)-2-hydroxy acid dehydrogenase, (R)-2-keto acid reductase and glucose dehydrogenase. One enantiomer [(S)-2-hydroxy acid] is firstly oxidized to the keto acid with (S)-2-hydroxy acid dehydrogenase, while the other enantiomer [(R)-2-hydroxy acid] remains unchanged. Then, the keto acid obtained reduced to the opposite enantiomer with (R)-2-keto acid reductase plus cofactor regeneration enzyme glucose dehydrogenase subsequently. The recombinant E. coli strain coexpressing the three enzymes was proven to be a promising biocatalyst for the cascade bioconversion of a structurally diverse range of racemic 2-hydroxy acids, giving the corresponding (R)-2-hydroxy acids in up to 98.5 % conversion and >99 % enantiomeric excess. CONCLUSIONS: In summary, a cascade biocatalysis was successfully developed to prepare valuable (R)-2-hydroxy acids with an efficient three-enzyme system. The developed elegant cascade biocatalysis possesses high atom efficiency and represents a promising strategy for production of highly valued (R)-2-hydroxy acids. PMID- 27659411 TI - The use of 68 Ga-PSMA PET CT in men with biochemical recurrence after definitive treatment of acinar prostate cancer. AB - INTRODUCTION: Early localisation of disease recurrence after definitive treatment of prostate cancer is vital to determine suitability for salvage treatment. Our aim was to further investigate the relationship between prostate specific antigen (PSA) level and detection of suspected cancer recurrence using 68 Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy (RP) or radiotherapy, particularly at low PSA levels. METHODS: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68 Ga PSMA PET/CT scans for investigation of post RP and post radiotherapy PSA recurrence following primary treatment of prostate cancer. We included men with suspected recurrent prostate cancer based on an elevated post treatment PSA level. The data collected analyzed the relationship of the pre-scan PSA level to the probability of a positive scan finding for recurrent prostate cancer. RESULTS: Of the cohort of 532 men, 425 had a previous RP and 107 had prior radiotherapy. The median PSA of the RP group was 0.59 ng/mL and 5.8 ng/mL in the radiotherapy group. In the post RP cohort, the detection rate of 68 Ga-PSMA PET/CT was 11.3% for PSA 0.01 to <0.2 ng/mL, 26.6% for PSA 0.2 to <0.5 ng/mL, 53.3% for PSA 0.5 to <1 ng/mL, 79.1% for PSA 1 to <2 ng/mL and 95.5% for PSA >=2. Lymph node metastasis post RP was identified in 68% of men with suspected disease recurrence. In the post radiotherapy cohort the detection rate was 33.3% for PSA 0.01 to <0.5 ng/mL, 71.4% for PSA 0.5 to <1 ng/mL, 93.3% for PSA 1 to <2 ng/mL and 100% for PSA >=2. Local recurrence after radiotherapy was suspected in 71% of the cohort and 40% had suspected lymph node metastasis. CONCLUSIONS: To our knowledge, this is largest cohort study of detection rates of 68 Ga-PSMA PET/CT in patients with biochemical recurrence after definitive treatment of prostate cancer, including patients with PSA <0.5 and in a post radiotherapy cohort. Detection of suspected recurrent disease outside the pelvis at low PSA levels will influence the decision for salvage treatment options. PMID- 27659412 TI - solveME: fast and reliable solution of nonlinear ME models. AB - BACKGROUND: Genome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope and predictive capabilities of constraint-based modeling. ME models present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints. RESULTS: Here, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60* speedup) via solver warm starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints. CONCLUSIONS: Just as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields. PMID- 27659413 TI - Difficulties in auditory organization as a cause of reading backwardness? An auditory neuroscience perspective. AB - Over 30 years ago, it was suggested that difficulties in the 'auditory organization' of word forms in the mental lexicon might cause reading difficulties. It was proposed that children used parameters such as rhyme and alliteration to organize word forms in the mental lexicon by acoustic similarity, and that such organization was impaired in developmental dyslexia. This literature was based on an 'oddity' measure of children's sensitivity to rhyme (e.g. wood, book, good) and alliteration (e.g. sun, sock, rag). The 'oddity' task revealed that children with dyslexia were significantly poorer at identifying the 'odd word out' than younger children without reading difficulties. Here we apply a novel modelling approach drawn from auditory neuroscience to study the possible sensory basis of the auditory organization of rhyming and non-rhyming words by children. We utilize a novel Spectral-Amplitude Modulation Phase Hierarchy (S AMPH) approach to analysing the spectro-temporal structure of rhyming and non rhyming words, aiming to illuminate the potential acoustic cues used by children as a basis for phonological organization. The S-AMPH model assumes that speech encoding depends on neuronal oscillatory entrainment to the amplitude modulation (AM) hierarchy in speech. Our results suggest that phonological similarity between rhyming words in the oddity task depends crucially on slow (delta band) modulations in the speech envelope. Contrary to linguistic assumptions, therefore, auditory organization by children may not depend on phonemic information for this task. Linguistically, it is assumed that 'book' does not rhyme with 'wood' and 'good' because the final phoneme differs. However, our auditory analysis suggests that the acoustic cues to this phonological dissimilarity depend primarily on the slower amplitude modulations in the speech envelope, thought to carry prosodic information. Therefore, the oddity task may help in detecting reading difficulties because phonological similarity judgements about rhyme reflect sensitivity to slow amplitude modulation patterns. Slower amplitude modulations are known to be detected less efficiently by children with dyslexia. PMID- 27659414 TI - One-month stability study of a biosimilar of infliximab (Remsima(r)) after dilution and storage at 4 degrees C and 25 degrees C. AB - There is currently only one monoclonal antibody for which there is a biosimilar: infliximab, which was released onto the French market in 2015. The SPC for the biosimilar (Remsima(r)) are superimposable on those of the original, including 24 hour stability at both 4 and 25 degrees C. The aim of our study was to determine the stability of this biosimilar during one month at 4 and 25 degrees C. Three different batches at two concentrations (0.7mg/mL or 1.6mg/mL) were used. Physicochemical stability was evaluated by the following methods: turbidity, UV spectrometry, DLS, ion chromatography (CEX), gel exclusion chromatography (SEC), and light microscopy. The analyses were performed in triplicate. All methods used have been demonstrated to be valid for measuring antibody stability. There were no signs of physicochemical instability after seven days (on D7) of storage at 4 or 25 degrees C. From D15, we observed slight changes by ion (percentage distribution of the different isoforms) and gel exclusion chromatography (percentage distribution of different polymers, i.e. dimers, oligomers). However, the areas under the curves were unchanged, and the proportions of polymers remained lower than 0.5%. Tertiary structure analysis also showed a change from D15. All observed changes are consistent with progressive oligomerization by hydrophobic interactions. In conclusion, the reconstituted biosimilar is stable for seven days at 4 and 25 degrees C. Gradual oligomerization is observed from D15 but appears to be less than 0.5%, suggesting instability, albeit very limited, in the longer term; the practical consequences of this remain to be evaluated. PMID- 27659416 TI - Liquid chromatography and tandem mass spectrometry method for quantitative determination of pioglitazone and its metabolite 5-hydroxy pioglitazone in human plasma. AB - A liquid chromatography tandem mass spectrometry (LC-MS/MS) based method was developed for the simultaneous estimation of pioglitazone and its active metabolites in human plasma for applicability to pharmacokinetic studies. The chromatographic separation was carried on the reversed phase Peerless Basic C18, column (100*4.6mm, 5MUm) at column temperature of 40 degrees C using a binary mobile phase consisting of methanol: 5mM ammonium acetate in 0.1% formic acid (80:20, v/v). The mobile phase was run at a flow rate of 1mL/min and the sample injection was 10MUL. The method utilized pioglitazone D4 (IS1) and 5-hydroxyl pioglitazone M-IV D4 (IS2) as an internal standard. The linearity of the method was validated over the range of 6.04-1503.21ng/mL for pioglitazone and 6.01 1496.28ng/mL for 5-hydroxyl pioglitazone. The mean extraction recovery of PIO & HPIO from the spiked plasma was found to be 94.92% for pioglitazone and 96.13% for 5-hydroxy pioglitazone. The developed method can be successfully employed in healthy human volunteers to monitor the pharmacokinetics profile of pioglitazone. PMID- 27659415 TI - [A pilot study of the professional ethical thinking of Quebec hospital pharmacists and pharmacy students]. AB - OBJECTIVE: The main objective was to assess the position of Quebec pharmaceutical community about pharmaceutical ethics statements. The second objective was to compare the level of agreement of pharmacy students and hospitals pharmacists. METHOD: Survey conducted one day given in 2012 and 2013 for students in 2013 and from 29/08/2014 to 02/09/2014 for pharmacists. A questionnaire of eight themes and 43 statements was developed: training and education (5 questions), clinical research (7) advertising and marketing (5) evaluation (5) dispensing medication (4), pharmaceutical care (9) economic aspect (6) and code of ethics (2). A Likert scale with four choices was used to measure the level of agreement. The primary outcome was the difference between the level of agreement of pharmacy students and hospital pharmacists. The Chi2 test was used. RESULTS: A total of 347 students and 398 pharmacists responded to the survey. There was a statistically significant difference regarding the level of agreement with 28 statements on 43. The differences focused on eight themes of the questionnaire, or training and education (3/5 significantly different questions), clinical research (2/7), advertising and marketing (2/5), Evaluation (4/5) dispensing medication (4/4), pharmaceutical care (5/9), economic aspect (6/6) and ethics (2/2). CONCLUSION: This study shows that there is a difference between pharmacists and pharmacy students about pharmaceutical ethics statements. PMID- 27659417 TI - Dermoscopy of acute cutaneous leishmaniasis. PMID- 27659418 TI - Change in soil fungal community structure driven by a decline in ectomycorrhizal fungi following a mountain pine beetle (Dendroctonus ponderosae) outbreak. AB - Western North American landscapes are rapidly being transformed by forest die-off caused by mountain pine beetle (Dendroctonus ponderosae), with implications for plant and soil communities. The mechanisms that drive changes in soil community structure, particularly for the highly prevalent ectomycorrhizal fungi in pine forests, are complex and intertwined. Critical to enhancing understanding will be disentangling the relative importance of host tree mortality from changes in soil chemistry following tree death. Here, we used a recent bark beetle outbreak in lodgepole pine (Pinus contorta) forests of western Canada to test whether the effects of tree mortality altered the richness and composition of belowground fungal communities, including ectomycorrhizal and saprotrophic fungi. We also determined the effects of environmental factors (i.e. soil nutrients, moisture, and phenolics) and geographical distance, both of which can influence the richness and composition of soil fungi. The richness of both groups of soil fungi declined and the overall composition was altered by beetle-induced tree mortality. Soil nutrients, soil phenolics and geographical distance influenced the community structure of soil fungi; however, the relative importance of these factors differed between ectomycorrhizal and saprotrophic fungi. The independent effects of tree mortality, soil phenolics and geographical distance influenced the community composition of ectomycorrhizal fungi, while the community composition of saprotrophic fungi was weakly but significantly correlated with the geographical distance of plots. Taken together, our results indicate that both deterministic and stochastic processes structure soil fungal communities following landscape-scale insect outbreaks and reflect the independent roles tree mortality, soil chemistry and geographical distance play in regulating the community composition of soil fungi. PMID- 27659419 TI - Foxp3 promoter methylation impairs suppressive function of regulatory T cells in biliary atresia. AB - Biliary atresia (BA) is characterized by progressive inflammation of the biliary system leading to liver cirrhosis, necessitating liver transplantation in pediatric patients. Various cell types have been reported to participate in the proinflammatory response in rhesus rotavirus (RRV)-induced BA mouse models, including T helper (Th) 1, Th2, Th17, CD8+ T cells, and natural killer cells. The immune suppressive regulatory T (Treg) cells, on the contrary, were reported not to function properly. The underlying mechanism is largely unknown. Focusing on the impaired suppressive function of Treg, we found methylation status of CpG islands within the Foxp3 promoter region of Treg cells in BA patients and murine models were both increased. Moreover, by injecting 5-aza-2'-deoxycytidine (Aza) as DNA-methylation inhibitor to RRV-infected mice, BA phenotypes were alleviated. Furthermore, Treg cells isolated from "RRV+Aza"-injected mice had better suppressive function than Treg cells from mice injected with RRV only, both in vivo and ex vivo. Thus we concluded that aberrant increased methylation status of "Foxp3 promoter" in Treg cells leads to impaired Treg suppressive function, exacerbating inflammatory injury in BA. PMID- 27659420 TI - Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly. AB - Glycosylation is involved in various pathophysiological conditions. N Acetylglucosaminyltransferase V (GnT-V), catalyzing beta1-6 branching in asparagine-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on high density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants. The study also included 96 patients who underwent medical health check-ups. Total serum cholesterol levels, particularly HDL-cholesterol (HDL-C) levels, were significantly increased in Tg vs. wild-type (WT) mice. Hepatic expression of apolipoprotein AI (ApoAI) and ATP-binding cassette subfamily A member 1 (ABCA1), two important factors in HDL assembly, were higher in Tg mice compared with WT mice. ApoAI and ABCA1 were also significantly elevated in GnT-V transfectants compared with mock-transfected cells. Moreover, ApoAI protein in the cultured media of GnT-V transfectants was significantly increased. Finally, we found a strong correlation between serum GnT-V activity and HDL-C concentration in human subjects. Multivariate logistic analyses demonstrated that GnT-V activity was an independent and significant determinant for serum HDL-C levels even adjusted with age and gender differences. Further analyses represented that serum GnT-V activity had strong correlation especially with the large-size HDL particle concentration. These findings indicate that enhanced hepatic GnT-V activity accelerated HDL assembly and could be a novel mechanism for HDL synthesis. PMID- 27659421 TI - Imaging activation of peptidergic spinal afferent varicosities within visceral organs using novel CGRPalpha-mCherry reporter mice. AB - In vertebrates, visceral pain from internal organs is detected by spinal afferents, whose cell bodies lie in dorsal root ganglia (DRG). Until now, all recordings from spinal afferents have been restricted to recording transmission of action potentials along axons, or from cell bodies lying outside their target organ, which is not where sensory transduction occurs. Our aim was to record directly from a major class of spinal afferent within visceral organs, where transduction of sensory stimuli into action potentials occurs. Using novel calcitonin gene-related peptide (CGRP)alpha reporter mice, DRG neurons expressed mCherry, including nerve axons within viscera. In colon, a minority of total CGRP immunoreactivity was attributed CGRPalpha. In isolated unstretched colon, calcium imaging from CGRPalpha-expressing varicose axons did not detect resolvable calcium transients. However, noxious levels of maintained circumferential stretch to the colon induced repetitive calcium transients simultaneously in multiple neighboring varicosities along single mCherry-expressing axons. Discrete varicosities could generate unitary calcium transients independently of neighboring varicosities. However, axons expressing mCherry only generated coordinated calcium transients when accompanied by simultaneous activation of multiple varicosities along that axon. Simultaneous imaging from different classes of myenteric neurons at the same time as mCherry-expressing axons revealed coordinated calcium transients in multiple myenteric neurons, independent of activity in mCherry-expressing axons. CGRPalpha-expressing axon terminals preferentially responded to heat, capsaicin, and low pH. We show that direct recordings can be made from the major class of peptidergic spinal afferent that contributes to visceral nociception. This approach can provide powerful insights into transduction of stimuli in viscera. PMID- 27659422 TI - Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling. AB - High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm2) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 +/- 0.1 mm/s to 7.5 +/- 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 +/- 0.1 mV to 2.5 +/- 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration. PMID- 27659424 TI - Glycine prevents metabolic steatohepatitis in diabetic KK-Ay mice through modulation of hepatic innate immunity. AB - Strategies for prevention and treatment of nonalcoholic steatohepatitis remain to be established. We evaluated the effect of glycine on metabolic steatohepatitis in genetically obese, diabetic KK-Ay mice. Male KK-Ay mice were fed a diet containing 5% glycine for 4 wk, and liver pathology was evaluated. Hepatic mRNA levels for lipid-regulating molecules, cytokines/chemokines, and macrophage M1/M2 markers were determined by real-time RT-PCR. Hepatic expression of natural killer (NK) T cells was analyzed by flow cytometry. Body weight gain was significantly blunted and development of hepatic steatosis and inflammatory infiltration were remarkably prevented in mice fed the glycine-containing diet compared with controls. Indeed, hepatic induction levels of molecules related to lipogenesis were largely blunted in the glycine diet-fed mice. Elevations of hepatic mRNA levels for TNFalpha and chemokine (C-C motif) ligand 2 were also remarkably blunted in the glycine diet-fed mice. Furthermore, suppression of hepatic NK T cells was reversed in glycine diet-fed KK-Ay mice, and basal hepatic expression levels of NK T cell-derived cytokines, such as IL-4 and IL-13, were increased. Moreover, hepatic mRNA levels of arginase-1, a marker of macrophage M2 transformation, were significantly increased in glycine diet-fed mice. In addition, dietary glycine improved glucose tolerance and hyperinsulinemia in KK Ay mice. These observations clearly indicate that glycine prevents maturity-onset obesity and metabolic steatohepatitis in genetically diabetic KK-Ay mice. The underlying mechanisms most likely include normalization of hepatic innate immune responses involving NK T cells and M2 transformation of Kupffer cells. It is proposed that glycine is a promising immunonutrient for prevention and treatment of metabolic syndrome-related nonalcoholic steatohepatitis. PMID- 27659425 TI - Separation of polyethylene glycols and maleimide-terminated polyethylene glycols by reversed-phase liquid chromatography under critical conditions. AB - The separation of polyethylene glycols and maleimide-substituted polyethylene glycol derivatives based on the number of maleimide end-groups under critical liquid chromatography conditions has been investigated on a reversed-phase column. The critical solvent compositions for nonfunctional polyethylene glycols and bifunctional maleimide-substituted polyethylene glycols were determined to be identical at about 40% acetonitrile in water on a reversed-phase octadecyl carbon chain-bonded silica column using mixtures of acetonitrile and water of varying composition as the mobile phase at 25 degrees C. The maleimide-functionalized polyethylene glycols were successfully separated according to maleimide functionality (with zero, one, two, or three maleimide end-groups, respectively) under the critical isocratic elution conditions without obvious effect of molar mass. The separation was mainly due to the hydrophobic interaction between the maleimide end-groups and the column packing. Off-line matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to identify the repeating units and, especially, the end-groups of the maleimide-substituted polyethylene glycols. Liquid chromatography analysis at critical conditions could provide useful information to optimize the synthesis of functional polyethylene glycols. To our knowledge, this is the first report of the baseline separation of maleimide-functionalized polyethylene glycols based on the functionality independent of the molar mass without derivatization by isocratic elution. PMID- 27659423 TI - A novel transgenic mouse model of lysosomal storage disorder. AB - Knockout technology has proven useful for delineating functional roles of specific genes. Here we describe and provide an explanation for striking pathology that occurs in a subset of genetically engineered mice expressing a rat CaVbeta2a transgene under control of the cardiac alpha-myosin heavy chain promoter. Lesions were limited to mice homozygous for transgene and independent of native Cacnb2 genomic copy number. Gross findings included an atrophied pancreas; decreased adipose tissue; thickened, orange intestines; and enlarged liver, spleen, and abdominal lymph nodes. Immune cell infiltration and cell engulfment by macrophages were associated with loss of pancreatic acinar cells. Foamy macrophages diffusely infiltrated the small intestine's lamina propria, while similar macrophage aggregates packed liver and splenic red pulp sinusoids. Periodic acid-Schiff-positive, diastase-resistant, iron-negative, Oil Red O positive, and autofluorescent cytoplasm was indicative of a lipid storage disorder. Electron microscopic analysis revealed liver sinusoids distended by clusters of macrophages containing intracellular myelin "swirls" and hepatocytes with enlarged lysosomes. Additionally, build up of cholesterol, cholesterol esters, and triglycerides, along with changes in liver metabolic enzyme levels, were consistent with a lipid processing defect. Because of this complex pathology, we examined the transgene insertion site. Multiple transgene copies inserted into chromosome 19; at this same site, an approximate 180,000 base pair deletion occurred, ablating cholesterol 25-hydroxylase and partially deleting lysosomal acid lipase and CD95 Loss of gene function can account for the altered lipid processing, along with hypertrophy of the immune system, which define this phenotype, and serendipitously provides a novel mouse model of lysosomal storage disorder. PMID- 27659427 TI - Neurodegeneration and RNA-binding proteins. AB - In the eukaryotic nucleus, RNA-binding proteins (RBPs) play a very important role in the life cycle of both coding and noncoding RNAs. As soon as they are transcribed, in fact, all RNA molecules within a cell are bound by distinct sets of RBPs that have the task of regulating its correct processing, transport, stability, and function/translation up to its final degradation. These tasks are particularly important in cells that have a complex RNA metabolism, such as neurons. Not surprisingly, therefore, recent findings have shown that the misregulation of genes involved in RNA metabolism or the autophagy/proteasome pathway plays an important role in the onset and progression of several neurodegenerative diseases. In this article, we aim to review the recent advances that link neurodegenerative processes and RBP proteins. WIREs RNA 2017, 8:e1394. doi: 10.1002/wrna.1394 For further resources related to this article, please visit the WIREs website. PMID- 27659426 TI - Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology: description and application to clinical feedback systems. AB - BACKGROUND: Health information technologies (HIT) have become nearly ubiquitous in the contemporary healthcare landscape, but information about HIT development, functionality, and implementation readiness is frequently siloed. Theory-driven methods of compiling, evaluating, and integrating information from the academic and commercial sectors are necessary to guide stakeholder decision-making surrounding HIT adoption and to develop pragmatic HIT research agendas. This article presents the Health Information Technologies-Academic and Commercial Evaluation (HIT-ACE) methodology, a structured, theory-driven method for compiling and evaluating information from multiple sectors. As an example demonstration of the methodology, we apply HIT-ACE to mental and behavioral health measurement feedback systems (MFS). MFS are a specific class of HIT that support the implementation of routine outcome monitoring, an evidence-based practice. RESULTS: HIT-ACE is guided by theories and frameworks related to user centered design and implementation science. The methodology involves four phases: (1) coding academic and commercial materials, (2) developer/purveyor interviews, (3) linking putative implementation mechanisms to hit capabilities, and (4) experimental testing of capabilities and mechanisms. In the current demonstration, phase 1 included a systematic process to identify MFS in mental and behavioral health using academic literature and commercial websites. Using user-centered design, implementation science, and feedback frameworks, the HIT ACE coding system was developed, piloted, and used to review each identified system for the presence of 38 capabilities and 18 additional characteristics via a consensus coding process. Bibliometic data were also collected to examine the representation of the systems in the scientific literature. As an example, results are presented for the application of HIT-ACE phase 1 to MFS wherein 49 separate MFS were identified, reflecting a diverse array of characteristics and capabilities. CONCLUSIONS: Preliminary findings demonstrate the utility of HIT ACE to represent the scope and diversity of a given class of HIT beyond what can be identified in the academic literature. Phase 2 data collection is expected to confirm and expand the information presented and phases 3 and 4 will provide more nuanced information about the impact of specific HIT capabilities. In all, HIT ACE is expected to support adoption decisions and additional HIT development and implementation research. PMID- 27659429 TI - Stem Cell Transplantation in Multiple Myeloma. AB - High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT. Moreover, the positive results obtained with these agents in consolidation and maintenance strategies after ASCT strongly support the concept of continuous therapy, whose ultimate goal is the long-term control of the disease and the improvement of outcome. Preliminary data from studies investigating next generation proteasome inhibitors, such as carfilzomib and ixazomib, used upfront as well as at subsequent therapeutic lines, demonstrate the possibility of achieving molecular remission in most of the patients. The deeper responses obtained with new drugcombinations questioned the role of ASCT, and large, ongoing, phase 3 trials will shed light on the role and the timing of ASCT. PMID- 27659430 TI - UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp GalNAc-T6): Role in Cancer and Prospects as a Drug Target. AB - UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer. Abnormally glycosylated forms of mucin 1 (a substrate of the enzyme), are used clinically as a biomarker for breast cancer. There is potential for other products of the pp-GalNAc- T6 catalyzed reaction to be used. It is also possible that pp-GalNAc-T6 itself could be used as a biomarker, since levels of this protein tend to be low in non malignant tissues. pp- GalNAc-T6 has been implicated in malignant transformation and metastasis of cancer cells. As such, it has considerable potential as a target for chemotherapy. To date, no selective inhibitors of the enzyme have been identified. However, general inhibitors of the enzyme family result in reduced cell surface O-linked glycosylation and induce apoptosis in cultured cells. Thus, a selective inhibitor of pp-GalNAc-T6 is likely to target cancer cells and could be developed into a novel anticancer therapy. PMID- 27659428 TI - Prevention of allograft rejection in heart transplantation through concurrent gene silencing of TLR and Kinase signaling pathways. AB - Toll-like receptors (TLRs) act as initiators and conductors responsible for both innate and adaptive immune responses in organ transplantation. The mammalian target of rapamycin (mTOR) is one of the most critical signaling kinases that affects broad aspects of cellular functions including metabolism, growth, and survival. Recipients (BALB/c) were treated with MyD88, TRIF and mTOR siRNA vectors, 3 and 7 days prior to heart transplantation and 7, 14 and 21 days after transplantation. After siRNA treatment, recipients received a fully MHC mismatched C57BL/6 heart. Treatment with mTOR siRNA significantly prolonged allograft survival in heart transplantation. Moreover, the combination of mTOR siRNA with MyD88 and TRIF siRNA further extended the allograft survival; Flow cytometric analysis showed an upregulation of FoxP3 expression in spleen lymphocytes and a concurrent downregulation of CD40, CD86 expression, upregulation of PD-L1 expression in splenic dendritic cells in MyD88, TRIF and mTOR treated mice. There is significantly upregulated T cell exhaustion in T cells isolated from tolerant recipients. This study is the first demonstration of preventing immune rejection of allogeneic heart grafts through concurrent gene silencing of TLR and kinase signaling pathways, highlighting the therapeutic potential of siRNA in clinical transplantation. PMID- 27659432 TI - Risk Factors for Urethral Condyloma among Heterosexual Young Male Patients with Condyloma Acuminatum of Penile Skin. AB - To our knowledge, this is the first study that focuses on risk factor of urethral condyloma (UC). The subjects of our study included genital warts patients who had been diagnosed as having condyloma acuminatum of penile skin (CAPS) with/without UC. Relationship with UC of number of life time female partners, co-infection with urethritis, circumcision status, number of CAPS and wart diameter were studied by use of multivariate analysis. Co-infection with urethritis, circumcision status were risk factors of UC in heterosexual young male patients with CAPS. This information will be helpful for providing more professional counseling to patients with genital warts. PMID- 27659431 TI - Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children. AB - BACKGROUND: The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic resistant bacteria in bacteremia diagnosed in febrile neutropenic children. MATERIALS AND METHODS: The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 and 2014 were retrospectively reviewed. The causative bacteria and proportion of antibiotic-resistant bacteria were investigated and compared yearly during the study period. The clinical impact of antibiotic-resistant bacterial infections was also determined. RESULTS: A total of 336 bacteremia episodes were identified. During the entire study period, 181 (53.9%) and 155 (46.1%) episodes were caused by Gram-negative and Gram-positive bacteria, respectively. Viridans streptococci (25.9%), Klebsiella spp. (16.7%), and Escherichia coli (16.4%) were the most frequent causative bacteria. The overall distribution of causative bacteria was not significantly different annually. Antibiotic-resistant bacteria were identified in 85 (25.3%) episodes, and the proportion of antibiotic-resistant bacteria was not significantly different annually. Extended-spectrum beta-lactamase-producing E. coli and Klebsiella spp. were most common among antibiotic-resistant Gram-negative bacteria, and they accounted for 30.6% (n = 34) of the identified E. coli and K. pneumoniae. Methicillin-resistant coagulase-negative staphylococci were most common among antibiotic-resistant Gram-positive bacteria, and it accounted for 88.5% (n = 23) of the identified coagulase-negative staphylococci. Antibiotic resistant bacterial infections, especially antibiotic-resistant Gram-negative bacterial infections, caused significantly higher mortality due to bacteremia compared with non-antibiotic-resistant bacterial infections (P < 0.001). CONCLUSION: Recently, Gram-negative bacteria caused more bacteremia cases than Gram-positive bacteria in febrile neutropenic children, and antibiotic-resistant Gram-negative bacterial infections increased. Antibiotic-resistant bacterial infections caused poorer prognosis compared with non-antibiotic-resistant bacterial infections, and therefore, continuous surveillance for changing epidemiology of antibiotic-resistant bacterial infections and their clinical impact is necessary. PMID- 27659433 TI - Olecranon Osteomyelitis due to Actinomyces meyeri: Report of a Culture-Proven Case. AB - Actinomyces meyeri is a Gram positive, strict anaerobic bacterium, which was first described by Meyer in 1911. Primary actinomycotic osteomyelitis is rare and primarily affects the cervicofacial region, including mandible. We present an unusual case of osteomyelitis of a long bone combined with myoabscess due to A. meyeri. A 70-year-old man was admitted for pain and pus discharge of the right elbow. Twenty-five days before admission, he had hit his elbow against a table. MRI of the elbow showed a partial tear of the distal triceps tendon and myositis. He underwent open debridement and partial bone resection for the osteomyelitis of the olecranon. Biopsy showed no sulfur granules, but acute and chronic osteomyelitis. The excised tissue grew A. meyeri and Peptoniphilus asaccharolyticus. Intravenous ceftriaxone was administered and switched to oral amoxicillin. Infection of the extremities of actinomycosis often poses diagnostic difficulties, but it should not be neglected even when the characteristic pathologic findings are not present. PMID- 27659435 TI - Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections. AB - BACKGROUND: For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients' characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections. MATERIALS AND METHODS: At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) <=50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P < 0.05 for selection and P < 0.01 for elimination. RESULTS: Both piperacillin PK and tazobactam PK were well described by a two compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 * CL(cr) /47 for piperacillin and CL = 1.76 + 4.81 * CL(cr) /47 for tazobactam. V1 was defined as V1 = 19.5 * weight/60 for piperacillin and V1 = 22.6 * weight/60 for tazobactam. CONCLUSION: The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance. PMID- 27659434 TI - Mortality Risk Factors for Patients with Septic Shock after Implementation of the Surviving Sepsis Campaign Bundles. AB - BACKGROUND: Septic shock remains a leading cause of death, despite advances in critical care management. The Surviving Sepsis Campaign (SSC) has reduced morbidity and mortality. This study evaluated risk factors for mortality in patients with septic shock who received treatment following the SSC bundles. MATERIALS AND METHODS: This retrospective cohort study included patients with septic shock who received treatments following SSC bundles in an urban emergency department between November 2007 and November 2011. Primary and secondary endpoints were all-cause 7- and 28-day mortality. RESULTS: Among 436 patients, 7- and 28-day mortality rates were 7.11% (31/436) and 14% (61/436), respectively. In multivariate analysis, high lactate level (odds ratio [OR], 1.286; 95% confidence interval [CI], 1.016-1.627; P=0.036) and low estimated glomerular filtration rate (OR, 0.953; 95% CI, 0.913-0.996; P=0.032) were independent risk factors for 7-day mortality. Risk factors for 28-day mortality were high lactate level (OR, 1.346; 95% CI, 1.083-1.673; P=0.008) and high Acute Physiology and Chronic Health Evaluation II score (OR, 1.153; 95% CI, 1.029-1.293; P=0.014). CONCLUSION: The risk of mortality of septic shock patients remains high in patients with high lactate levels and acute kidney injury. PMID- 27659436 TI - Carbapenem-resistant Enterobacteriaceae: Prevalence and Risk Factors in a Single Community-Based Hospital in Korea. AB - BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria with increasing prevalence of infection worldwide. In Korea, 25 cases of CPE isolates were reported by the Korea Centers for Disease Control and Prevention in 2011. Most CPE cases were detected mainly at tertiary referral hospitals. We analyzed the prevalence and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) in a mid-sized community-based hospital in Korea. MATERIALS AND METHODS: We retrospectively analyzed all consecutive episodes of Enterobacteriaceae in a mid-sized community-based hospital from January 2013 to February 2014. CRE was defined as organisms of Enterobacteriaceae showing decreased susceptibility to carbapenems. Risk factors for CRE were evaluated by a case-double control design. Carbapenemase was confirmed for CRE using a combined disc test. RESULTS: During 229,710 patient-days, 2,510 Enterobacteriaceae isolates were obtained. A total of 41 (1.6%) CRE isolates were enrolled in the study period. Thirteen species (31.7%) were Enterobacter aerogenes, 8 (19.5%) Klebsiella pneumoniae, 5 (12.2%) Enterobacter cloacae, and 15 other species of Enterobacteriaceae, respectively. Among the 41 isolates, only one (2.4%) E. aerogenes isolate belonged to CPE. For evaluation of risk factors, a total of 111 patients were enrolled and this included 37 patients in the CRE group, 37 in control group I (identical species), and 37 in control group II (different species). Based on multivariate analysis, regularly visiting the outpatient clinic was a risk factor for CRE acquisition in the control group I (P = 0.003), while vascular catheter and Charlson comorbidity index score >= 3 were risk factors in control group II (P = 0.010 and 0.011, each). Patients with CRE were more likely to experience a reduced level of consciousness, use a vasopressor, be under intensive care, and suffer from acute kidney injury. However, CRE was not an independent predictor of mortality compared with both control groups. CONCLUSION: In conclusion, the prevalence of CRE was higher than expected in a mid-sized community-based hospital in Korea. CRE should be considered when patients have a vascular catheter, high comorbidity score, and regular visits to the outpatient clinic. This study suggests the need for appropriate prevention efforts and constant attention to CRE infection control in a mid-sized community based hospital. PMID- 27659437 TI - A 5-year Surveillance Study on Antimicrobial Resistance of Acinetobacter baumannii Clinical Isolates from a Tertiary Greek Hospital. AB - BACKGROUND: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010-2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. MATERIALS AND METHODS: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to >=3 classes of antimicrobial agents. RESULTS: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to >=3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year. CONCLUSION: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed. PMID- 27659438 TI - A Case of Infective Endocarditis caused by Abiotrophia defectiva in Korea. AB - Abiotrophia defectiva, a nutritionally variant streptococci can cause bacteremia, brain abscess, septic arthritis and in rare cases, infective endocarditis, which accounts for 5-6% of all cases. A. defectiva is characteristically difficult to diagnose and the mortality, morbidity and complication rates are high. Here, we discuss a case of infective endocarditis caused by A. defectiva. A 62-year-old female had previously undergone prosthetic valve replacement 6 years prior to admission. She developed infective endocarditis after tooth extraction. Her endocarditis was successfully treated with antimicrobial therapy and mitral valve replacement surgery. This is the first case of infective endocarditis caused by A. defectiva reported in Korea. This case shows that A. defectiva could be considered as a causative organism of infective endocarditis in Korea. PMID- 27659439 TI - Native Valve Endocarditis due to Corynebacterium striatum confirmed by 16S Ribosomal RNA Sequencing: A Case Report and Literature Review. AB - Corynebacterium species are non-fermentous Gram-positive bacilli that are normal flora of human skin and mucous membranes and are commonly isolated in clinical specimens. Non-diphtheriae Corynebacterium are regarded as contaminants when found in blood culture. Currently, Corynebacterium striatum is considered one of the emerging nosocomial agents implicated in endocarditis and serious infections. We report a case of native-valve infective endocarditis caused by C. striatum, which was misidentified by automated identification system but identified accurately by 16S ribosomal RNA sequencing, in a 55-year-old male patient. The patient had two mobile vegetations on his mitral valve, both of which had high embolic risk. Through surgical valve replacement and an antibiotic regimen, the patient recovered completely. In unusual clinical scenarios, C. striatum should not be simply dismissed as a contaminant when isolated from clinical specimens. The possibility of C. striatum infection should be considered even in an immunocompetent patient, and we suggest a genotypic assay, such as 16S rRNA sequencing, to confirm species identity. PMID- 27659440 TI - Clinical and Economic Evaluation of Multidrug-Resistant Acinetobacter baumannii Colonization in the Intensive Care Unit. AB - BACKGROUND: The clinical and economic impact of multidrug-resistant (MDR) Acinetobacter baumannii colonization remains unclear. This study aimed to estimate and compare the mortality rates, length of stay (LOS), and hospitalization costs in the intensive care unit (ICU) for MDR A. baumannii colonized patients and a matched population. MATERIALS AND METHODS: We performed a retrospective propensity score matched cohort study comparing the outcomes of patients with MDR A. baumannii colonization with those of uncolonized subjects matched at the time they were admitted to the ICU between January 2012 and December 2014. RESULTS: During the study period, 375 (7.5%) of the 4,779 patients were colonized with MDR A. baumannii. One hundred and twenty-two MDR A. baumannii colonized patients were compared with 122 uncolonized patients using propensity score matching. MDR A. baumannii colonized patients were likely to have a higher mortality rate compared to uncolonized patients (49.2% vs 32.0%; odds ratio [OR], 3.64). A longer ICU LOS and total admission days were observed in the MDR A. baumannii colonized patient group (4.14 and 4.67 days increase, OR 1.41 and 1.19). MDR A. baumannii colonization patients had an average extra ICU and total admission cost of $1,179 (?1,261,334) and $1,333 (?1,422,032) according to a multivariable regression model (OR, 1.27 and 1.17). Multivariable analysis identified the factors affecting ICU cost, which included, MDR A. baumannii colonization (OR = 1.33; P = 0.001), ICU LOS (OR = 1.97; P <0.001), valvular heart disease (OR = 1.12; P = 0.005), invasive devices (OR = 1.15; P = 0.018), and surgery (OR = 1.1; P < 0.001). CONCLUSION: MDR A. baumannii colonization was associated with increased mortality, LOS, and costs in the ICU. A strict infection control program including preemptive isolation for high-risk groups would be helpful for reducing the burden of this infection. PMID- 27659441 TI - Cigarette Smoking Status and Receipt of an Opioid Prescription Among Veterans of Recent Wars. AB - Objective: Cigarette smokers seeking treatment for chronic pain have higher rates of opioid use than nonsmokers. This study aims to examine whether veterans of Operations Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) who smoke are more likely to receive an opioid prescription than nonsmokers, adjusting for current pain intensity. Design: Cross-sectional analysis of a cohort study of OEF/OIF/OND veterans who had at least one visit to a Veterans Health Administration primary care clinic between 2001 and 2012. Methods: Smoking status was defined as current, former, and never. Current pain intensity (+/- 30 days of smoking status), based on the 0-10 numeric rating scale, was categorized as no pain/mild (0-3) and moderate/severe (4-10). Opioid receipt was defined as at least one prescription filled +/- 30 days of smoking status. Results: We identified 406,954 OEF/OIF/OND veterans: The mean age was 30 years, 12.5% were women (n = 50,988), 66.3% reported no pain or mild pain intensity, 33.7% reported moderate or severe pain intensity, 37.2% were current smokers, and 16% were former smokers. Overall, 33,960 (8.3%) veterans received one or more opioid prescription. Current smoking (odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.52-1.61) and former smoking (OR = 1.27, 95% CI = 1.22-1.32) were associated with a higher likelihood of receipt of an opioid prescription compared with never smoking, after controlling for other covariates. Conclusions: We found an association between smoking status and receipt of an opioid prescription. The effect was stronger for current smokers than former smokers, highlighting the need to determine whether smoking cessation is associated with a reduction in opioid use among veterans. PMID- 27659442 TI - Autophagy activation involved in hypoxic-ischemic brain injury induces cognitive and memory impairment in neonatal rats. AB - Hypoxic-ischemic brain injury (HIBI) in neonates can lead to lifelong cognitive and memory impairment, but protective strategies are lacking at present. It has been demonstrated that autophagy plays a critical role in HIBI, while the function of autophagy in cognitive and memory impairment induced by HIBI in neonates has not been tested. In this study, we tested the impact of autophagy on the impairment of cognitive function and memory in HIBI neonatal rats by using a Morris water maze and investigated its possible mechanisms, which were established as HIBI model by ligating the left common carotid artery in neonatal rats, followed by 2-h hypoxia. The expression of microtubule-associated protein 1 light chain 3 (LC3)-II increased in HI group 24 h after HI in neonatal rats, while Sequestosome 1 (P62/SQSTM1), phosphorylated cAMP-response element-binding protein (p-CREB) decreased (compared with the sham group, p < 0.05), which were shown in the same left hippocampus CA3 region by immunofluorescence analysis. Brain injury of neonatal rats was aggravated significantly at 7 day after HI, coinciding with the results of Morris water maze. An autophagy inhibitor, 3 methyladenine (3-MA) pretreatment significantly attenuated the increase of LC3II and the loss of P62/SQSTM1 and p-CREB, ameliorated neuronal death, and improved the results of Morris water maze. Our results demonstrate that HIBI in neonatal rats induced excessive autophagy flux, which aggravated brain injury and induced cognitive and memory impairment during adolescence. Inhibition of autophagy reversed the results partly and improved the function of spatial learning and memory by attenuating the reduction of p-CREB. The use of autophagy modulators in the immature brain would create new opportunities for protective strategies clinically in the future. PMID- 27659443 TI - Metacarpal lengthening in children: comparison of three different techniques in 15 consecutive cases. AB - : Metacarpal lengthening is a useful procedure to address hand deficiencies in children. In this study, we aimed to compare the results of three different techniques from one consecutive clinical series of hand deficiencies. A total of 15 metacarpal lengthenings have been performed in 12 children aged from 9 to 14 years. The callotasis technique was used in seven cases, the two-stage distraction-graft technique in four cases and the single-stage lengthening in four cases. All the metacarpals healed with bone. The lengthening obtained was a mean of 13 mm (range 8-21 mm), a mean of 22 mm (range 13-32 mm) and a mean of 12 mm (range 9-15 mm), respectively, in the three different techniques. The healing index was longer for callotasis (81 days/cm) compared with the other techniques (41 days/cm and 46 days/cm, respectively). We observed one case of fracture after callotasis and one after distraction-graft. One patient underwent tenolysis of the extensor mechanism after single-stage lengthening. In conclusion, distraction graft and single-stage lengthening may be valuable alternatives to callotasis. LEVEL OF EVIDENCE: IV; therapeutic study; multi-case series. PMID- 27659444 TI - Single nanowire green InGaN/GaN light emitting diodes. AB - Single nanowire (NW) green InGaN/GaN light-emitting diodes (LEDs) were fabricated by top-down etching technology. The electroluminescence (EL) peak wavelength remains approximately constant with an increasing injection current in contrast to a standard planar LED, which suggests that the quantum-confined Stark effect is significantly reduced in the single NW device. The strain relaxation mechanism is studied in the single NW LED using Raman scattering analysis. As compared to its planar counterpart, the EL peak of the NW LED shows a redshift, due to electric field redistribution as a result of changes in the cavity mode pattern after metallization. Our method has important implication for single NW optoelectronic device applications. PMID- 27659445 TI - Quantum entanglement: facts and fiction - how wrong was Einstein after all? AB - Einstein was wrong with his 1927 Solvay Conference claim that quantum mechanics is incomplete and incapable of describing diffraction of single particles. However, the Einstein-Podolsky-Rosen paradox of entangled pairs of particles remains lurking with its 'spooky action at a distance'. In molecules quantum entanglement can be viewed as basis of both chemical bonding and excitonic states. The latter are important in many biophysical contexts and involve coupling between subsystems in which virtual excitations lead to eigenstates of the total Hamiltonian, but not for the separate subsystems. The author questions whether atomic or photonic systems may be probed to prove that particles or photons may stay entangled over large distances and display the immediate communication with each other that so concerned Einstein. A dissociating hydrogen molecule is taken as a model of a zero-spin entangled system whose angular momenta are in principle possible to probe for this purpose. In practice, however, spins randomize as a result of interactions with surrounding fields and matter. Similarly, no experiment seems yet to provide unambiguous evidence of remaining entanglement between single photons at large separations in absence of mutual interaction, or about immediate (superluminal) communication. This forces us to reflect again on what Einstein really had in mind with the paradox, viz. a probabilistic interpretation of a wave function for an ensemble of identically prepared states, rather than as a statement about single particles. Such a prepared state of many particles would lack properties of quantum entanglement that make it so special, including the uncertainty upon which safe quantum communication is assumed to rest. An example is Zewail's experiment showing visible resonance in the dissociation of a coherently vibrating ensemble of NaI molecules apparently violating the uncertainty principle. Einstein was wrong about diffracting single photons where space-like anti-bunching observations have proven recently their non-local character and how observation in one point can remotely affect the outcome in other points. By contrast, long range photon entanglement with immediate, superluminal response is still an elusive, possibly partly misunderstood issue. The author proposes that photons may entangle over large distances only if some interaction exists via fields that cannot propagate faster than the speed of light. An experiment to settle this 'interaction hypothesis' is suggested. PMID- 27659447 TI - Research on pediatric glomerular disease and normal kidney with shear wave based elastography point quantification. AB - PURPOSE: To evaluate the renal cortex stiffness in children with glomerular disease by shear wave based elastography point quantification (ElastPQ), and to investigate the association between shear wave velocity (SWV) in the renal cortex and age in normal children, and the inter-gender differences. MATERIALS AND METHODS: One hundred and five children who were pathologically confirmed with glomerular diseases were selected as the disease group. Meanwhile, 120 healthy children were selected as the control group. Effective values were measured 5 times at the same kidney sites on each side. RESULTS: Comparisons of SWV measurements between left and right kidneys in the disease and control groups all showed significant differences (left kidney t = 6.896, P = 0.004; right kidney t = 7.415, P = 0.001). In the control group, left and right kidney SWV measurements were all positively correlated with age (left kidney r = 0.792, P = 0.003; right kidney r = 0.794, P = 0.004). Moreover, inter-gender difference was present in the right kidney measurements. CONCLUSIONS: ElastPQ technology has certain advantages in predicting pediatric glomerular disease compared to conventional ultrasound. ElastPQ technology contributes to the early diagnosis of the disease. PMID- 27659446 TI - Organic cation transporter 3 (OCT3) is localized to intracellular and surface membranes in select glial and neuronal cells within the basolateral amygdaloid complex of both rats and mice. AB - Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunofluorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. OCT3-immunoreactivity was observed in both glial and neuronal perikarya in both rat and mouse amygdala. Electron microscopic immunolabeling revealed plasma membrane-associated OCT3 immunoreactivity on axonal, dendritic, and astrocytic processes adjacent to a variety of synapses, as well as on neuronal somata. In addition to plasma membrane sites, OCT3 immunolabeling was also observed associated with neuronal and glial endomembranes, including Golgi, mitochondrial and nuclear membranes. Particularly prominent labeling of the outer nuclear membrane was observed in neuronal, astrocytic, microglial and endothelial perikarya. The localization of OCT3 to neuronal and glial plasma membranes adjacent to synaptic sites is consistent with an important role for this transporter in regulating the amplitude, duration, and physical spread of released monoamines, while its localization to mitochondrial and outer nuclear membranes suggests previously undescribed roles for the transporter in the intracellular disposition of monoamines. PMID- 27659449 TI - Acute kidney injury after cardiac arrest: an unappreciated complication. PMID- 27659448 TI - Hypofractionated stereotactic radiotherapy (HFSRT) for who grade I anterior clinoid meningiomas (ACM). AB - PURPOSE: While microsurgical resection plays a central role in the management of ACMs, extensive surgery may be associated with substantial morbidity particularly for tumors in intimate association with critical structures. In this study, we evaluated the use of HFSRT in the management of ACM. MATERIALS AND METHODS: A total of 22 patients with ACM were treated using HFSRT. Frameless image guided volumetric modulated arc therapy (VMAT) was performed with a 6 MV linear accelerator (LINAC). The total dose was 25 Gy delivered in five fractions over five consecutive treatment days. Local control (LC) and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Common Terminology Criteria for Adverse Events, version 4.0 was used in toxicity grading. RESULTS: Out of the total 22 patients, outcomes of 19 patients with at least 36 months of periodic follow-up were assessed. Median patient age was 40 years old (range 24 77 years old). Median follow-up time was 53 months (range 36-63 months). LC and PFS rates were 100 and 89.4 % at 1 and 3 years, respectively. Only two patients (10.5 %) experienced clinical deterioration during the follow-up period. CONCLUSION: LINAC-based HFSRT offers high rates of LC and PFS for patients with ACMs. PMID- 27659450 TI - GeneEvolve: a fast and memory efficient forward-time simulator of realistic whole genome sequence and SNP data. AB - MOTIVATION: Computer simulations are excellent tools for understanding the evolutionary and genetic consequences of complex processes that cannot be analytically predicted and for creating realistic genetic data. There are many software packages that simulate genetic data, but they are typically not fast or memory efficient enough to simulate realistic, individual-level genome-wide SNP/sequence data. RESULTS: GeneEvolve is a user-friendly and efficient population genetics simulator that handles complex evolutionary and life history scenarios and generates individual-level phenotypes and realistic whole-genome sequence or SNP data. GeneEvolve runs forward-in-time, which allows it to provide a wide range of scenarios for mating systems, selection, population size and structure, migration, recombination and environmental effects. The software is designed to use as input data from real or previously simulated phased haplotypes, allowing it to mimic very closely the properties of real genomic data. AVAILABILITY AND IMPLEMENTATION: GeneEvolve is freely available at https://github.com/rtahmasbi/GeneEvolve CONTACT: Rasool.Tahmasbi@Colorado.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27659452 TI - TwoPaCo: an efficient algorithm to build the compacted de Bruijn graph from many complete genomes. AB - Motivation: de Bruijn graphs have been proposed as a data structure to facilitate the analysis of related whole genome sequences, in both a population and comparative genomic settings. However, current approaches do not scale well to many genomes of large size (such as mammalian genomes). Results: In this article, we present TwoPaCo, a simple and scalable low memory algorithm for the direct construction of the compacted de Bruijn graph from a set of complete genomes. We demonstrate that it can construct the graph for 100 simulated human genomes in less than a day and eight real primates in < 2 h, on a typical shared-memory machine. We believe that this progress will enable novel biological analyses of hundreds of mammalian-sized genomes. Availability and Implementation: Our code and data is available for download from github.com/medvedevgroup/TwoPaCo. Contact: ium125@psu.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 27659451 TI - PSSV: a novel pattern-based probabilistic approach for somatic structural variation identification. AB - MOTIVATION: Whole genome DNA-sequencing (WGS) of paired tumor and normal samples has enabled the identification of somatic DNA changes in an unprecedented detail. Large-scale identification of somatic structural variations (SVs) for a specific cancer type will deepen our understanding of driver mechanisms in cancer progression. However, the limited number of WGS samples, insufficient read coverage, and the impurity of tumor samples that contain normal and neoplastic cells, limit reliable and accurate detection of somatic SVs. RESULTS: We present a novel pattern-based probabilistic approach, PSSV, to identify somatic structural variations from WGS data. PSSV features a mixture model with hidden states representing different mutation patterns; PSSV can thus differentiate heterozygous and homozygous SVs in each sample, enabling the identification of those somatic SVs with heterozygous mutations in normal samples and homozygous mutations in tumor samples. Simulation studies demonstrate that PSSV outperforms existing tools. PSSV has been successfully applied to breast cancer data to identify somatic SVs of key factors associated with breast cancer development. AVAILABILITY AND IMPLEMENTATION: An R package of PSSV is available at http://www.cbil.ece.vt.edu/software.htm CONTACT: xuan@vt.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27659453 TI - Evolutionary conservation of Ebola virus proteins predicts important functions at residue level. AB - MOTIVATION: The recent outbreak of Ebola virus disease (EVD) resulted in a large number of human deaths. Due to this devastation, the Ebola virus has attracted renewed interest as model for virus evolution. Recent literature on Ebola virus (EBOV) has contributed substantially to our understanding of the underlying genetics and its scope with reference to the 2014 outbreak. But no study yet, has focused on the conservation patterns of EBOV proteins. RESULTS: We analyzed the evolution of functional regions of EBOV and highlight the function of conserved residues in protein activities. We apply an array of computational tools to dissect the functions of EBOV proteins in detail: (i) protein sequence conservation, (ii) protein-protein interactome analysis, (iii) structural modeling and (iv) kinase prediction. Our results suggest the presence of novel post-translational modifications in EBOV proteins and their role in the modulation of protein functions and protein interactions. Moreover, on the basis of the presence of ATM recognition motifs in all EBOV proteins we postulate a role of DNA damage response pathways and ATM kinase in EVD. The ATM kinase is put forward, for further evaluation, as novel potential therapeutic target. AVAILABILITY AND IMPLEMENTATION: http://www.biw.kuleuven.be/CSB/EBOV-PTMs CONTACT: vera.vannoort@biw.kuleuven.beSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27659454 TI - Cardiovascular PET/MR imaging: Quo Vadis? AB - With the recent advent of PET/MRI scanners, the combination of molecular imaging with a variety of known and novel PET radiotracers, the high spatial resolution of MRI, and its potential for multi-parametric imaging are anticipated to increase the diagnostic accuracy in cardiovascular disease detection, while providing novel mechanistic insights into the initiation and progression of the disease state. For the time being, cardiac PET/MRI emerges as potential clinical tool in the identification and characterization of infiltrative cardiac diseases, such as sarcoidosis, acute or chronic myocarditis, and cardiac tumors, respectively. The application of PET/MRI in conjunction with various radiotracer probes in the identification of the vulnerable atherosclerotic plaque also holds much promise but needs further translation and validation in clinical investigations. The combination of molecular imaging and creation of multi parametric imaging maps with PET/MRI, however, are likely to set new horizons to develop predictive parameters for myocardial recovery and treatment response in ischemic and non-ischemic cardiomyopathy patients. Molecular imaging and multi parametric imaging in cardiovascular disease with PET/MRI at current stage are at its infancy but bear a bright future. PMID- 27659456 TI - Prompt-gamma compensation in Rb-82 myocardial perfusion 3D PET/CT: Effect on clinical practice. PMID- 27659455 TI - PET/MR: Yet another Tesla? AB - After the successful introduction of PET/CT as a multimodality imaging technique, PET/MR has subsequently emerged as an attractive instrumentation for applications in neurology, oncology, and cardiology. Simultaneous data acquisition combining structural, functional, and molecular imaging provides a unique platform to link various aspects of cardiac performance for the non-invasive characterization of cardiovascular disease phenotypes. Specifically, tissue characterization by MR techniques with and without contrast agents allows for functional parameters such as LGE, myocardial perfusion, and T1 maps as well as an estimate of extracellular volume. PET tracers excel by their high sensitivity and specificity, thus supplementing the functional tissue characterization by MRI. Although the clinical applications are yet to be validated , the first experience with PET/MR suggests future applications in the area of vascular imaging (unstable plaque) as well as in the characterization of inflammatory processes involving the heart. Ischemic heart disease can be comprehensively assessed by integrating regional function, perfusion, and viability. Future technical improvements leading to less costly PET/MR instrumentation are necessary to support routine clinical application of this promising technique in cardiology. PMID- 27659457 TI - Prognostic significance of blood pressure response during vasodilator stress Rb 82 positron emission tomography myocardial perfusion imaging. AB - BACKGROUND: A drop in blood pressure (BP) or blunted BP response is an established high-risk marker during exercise myocardial perfusion imaging (MPI); however, data are sparse regarding the prognostic value of BP response in patients undergoing vasodilator stress rubidium-82 (Rb-82) Positron Emission Tomography (PET) MPI. METHODS AND RESULTS: From the PET Prognosis Multicenter Registry, a cohort of 3413 patients underwent vasodilator stress Rb-82 PET MPI with dipyridamole or adenosine. We used multivariable Cox proportional hazard regression to analyze the association with mortality of four BP variables: stress minus rest systolic BP (?SBP), stress minus rest diastolic BP (?DBP), resting systolic BP (rSBP), and resting diastolic BP (rDBP). Covariates that had univariate P values <.10 were entered into the multivariable model. After median 1.7 years follow-up, 270 patients died. In univariate analyses, ?SBP (P = .082), rSBP (P = .008), and rDBP (P < .001) were of potential prognostic value (P < .10), but ?DBP was not (P = .96). After adjustment for other clinical and MPI variables, ?SBP no longer independently predicted mortality (P = .082); only lower rSBP (P = .026) and lower rDBP (P = .045) remained independently prognostic. CONCLUSIONS: In patients undergoing vasodilator stress MPI, only lower resting BP is an independent predictor of mortality along with other clinical and MPI variables; BP response does not appear to add to risk stratification in these patients. PMID- 27659459 TI - Blood Pressure Variability: Insights From "Big Data". PMID- 27659458 TI - Association of Systolic Blood Pressure Variability With Mortality, Coronary Heart Disease, Stroke, and Renal Disease. AB - BACKGROUND: Intraindividual blood pressure (BP) fluctuates dynamically over time. Previous studies suggested an adverse link between greater visit-to-visit variability in systolic blood pressure (SBP) and various outcomes. However, these studies have significant limitations, such as a small size, inclusion of selected populations, and restricted outcomes. OBJECTIVES: This study investigated the association of increased visit-to-visit variability and all-cause mortality, cardiovascular events, and end-stage renal disease (ESRD) in a large cohort of U.S. veterans. METHODS: From among 3,285,684 U.S. veterans with and without hypertension and normal estimated glomerular filtration rates (eGFR) during 2005 and 2006, we identified 2,865,157 patients who had 8 or more outpatient BP measurements. Systolic blood pressure variability (SBPV) was measured using the SD of all SBP values (normally distributed) in 1 individual. Associations of SD quartiles (<10.3, 10.3 to 12.7, 12.7 to 15.6, and >=15.6 mm Hg) with all-cause mortality, incident coronary heart disease (CHD), stroke, and ESRD was examined using Cox models adjusted for sociodemographic characteristics, baseline eGFR, comorbidities, body mass index, SBP, diastolic BP, and antihypertensive medication use. RESULTS: Several sociodemographic variables (older age, male sex, African-American race, divorced or widowed status) and clinical characteristics (lower baseline eGFR, higher SBP and diastolic BP), and comorbidities (presence of diabetes, hypertension, cardiovascular disease, and lung disease) were all associated with higher intraindividual SBPV. The multivariable adjusted hazard ratios and 95% confidence intervals for SD quartiles 2 through 4 (compared with the first quartile) associated with all-cause mortality, CHD, stroke, and ESRD were incrementally higher. CONCLUSIONS: Higher SBPV in individuals with and without hypertension was associated with increased risks of all-cause mortality, CHD, stroke, and ESRD. Further studies are needed to determine interventions that can lower SBPV and their impact on adverse health outcomes. PMID- 27659460 TI - Thromboembolic, Bleeding, and Mortality Risks of Rivaroxaban and Dabigatran in Asians With Nonvalvular Atrial Fibrillation. AB - BACKGROUND: It is unclear whether the non-vitamin K antagonist oral anticoagulant agents rivaroxaban and dabigatran are superior to warfarin for efficacy and safety outcomes in Asians with nonvalvular atrial fibrillation (NVAF). OBJECTIVES: The aim of this study was to compare the risk for thromboembolic events, bleeding, and mortality associated with rivaroxaban and dabigatran versus warfarin in Asians with NVAF. METHODS: A nationwide retrospective cohort study was conducted of consecutive patients with NVAF taking rivaroxaban (n = 3,916), dabigatran (n = 5,921), or warfarin (n = 5,251) using data collected from the Taiwan National Health Insurance Research Database between February 1, 2013 and December 31, 2013. The propensity score weighting method was used to balance covariates across study groups. Patients were followed until the first occurrence of any study outcome or the study end date (December 31, 2013). RESULTS: A total of 3,425 (87%) and 5,301 (90%) patients were taking low-dose rivaroxaban (10 to 15 mg once daily) and dabigatran (110 mg twice daily), respectively. Compared with warfarin, both rivaroxaban and dabigatran significantly decreased the risk for ischemic stroke or systemic embolism (p = 0.0004 and p = 0.0006, respectively), intracranial hemorrhage (p = 0.0007 and p = 0.0005, respectively), and all-cause mortality (p < 0.0001 and p < 0.0001, respectively) during the short follow-up period. In comparing the 2 non-vitamin K antagonist oral anticoagulant agents with each other, no differences were found regarding risk for ischemic stroke or systemic embolism, intracranial hemorrhage, myocardial infarction, or mortality. Rivaroxaban carried a significantly higher risk for hospitalization for gastrointestinal bleeding than dabigatran (p = 0.0416), but on-treatment analysis showed that the risk for hospitalized gastrointestinal bleeding was similar between the 2 drugs (p = 0.5783). CONCLUSIONS: In real-world practice among Asians with NVAF, both rivaroxaban and dabigatran were associated with reduced risk for ischemic stroke or systemic embolism, intracranial hemorrhage, and all-cause mortality without significantly increased risk for acute myocardial infarction or hospitalization for gastrointestinal bleeding compared with warfarin. PMID- 27659461 TI - The Reality of "Real-World" Data: More Questions Than Answers. PMID- 27659462 TI - Prognostic Implications of Type 2 Diabetes Mellitus in Ischemic and Nonischemic Heart Failure. AB - BACKGROUND: Heart failure (HF) is a common and serious complication in type 2 diabetes mellitus (T2DM). The prognosis of ischemic HF and impact of revascularization in such patients have not been investigated fully in a patient population representing everyday practice. OBJECTIVES: This study examined the impact of ischemic versus nonischemic HF and previous revascularization on long term prognosis in an unselected population of patients with and without T2DM. METHODS: Patients stratified by diabetes status and ischemic or nonischemic HF and history of revascularization in the Swedish Heart Failure Registry (SwedeHF) from 2003 to 2011 were followed up for mortality predictors and longevity. A propensity score analysis was applied to evaluate the impact of previous revascularization. RESULTS: Among 35,163 HF patients, those with T2DM were younger, and 90% had 1 or more associated comorbidities. Ischemic heart disease (IHD) occurred in 62% of patients with T2DM and 47% of those without T2DM, of whom 53% and 48%, respectively, had previously undergone revascularization. T2DM predicted mortality regardless of the presence of IHD, with adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.40 (1.33 to 1.46) and 1.30 (1.22 to 1.39) in those with and without IHD, respectively. Patients with both T2DM and IHD had the highest mortality, which was further accentuated by the absence of previous revascularization (adjusted HR: 0.82 in favor of such treatment; 95% CI: 0.75 to 0.91). Propensity score adjustment did not change these results (HR: 0.87; 95% CI: 0.78 to 0.96). Revascularization did not abolish the impact of T2DM, which predicted mortality in those with (HR: 1.36; 95% CI: 1.24 to 1.48) and without (HR: 1.45; 95% CI: 1.33 to 1.56) a history of revascularization. CONCLUSIONS: Ninety percent of HF patients with T2DM have preventable comorbidities. IHD in patients with T2DM had an especially negative influence on mortality, an impact that was beneficially influenced by previous revascularization. PMID- 27659463 TI - Diabetes and Heart Failure: Sugared Words Prove Bitter. PMID- 27659464 TI - Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations: The AKINESIS Study. AB - BACKGROUND: Worsening renal function (WRF) often occurs during acute heart failure (AHF) and can portend adverse outcomes; therefore, early identification may help mitigate risk. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel renal biomarker that may predict WRF in certain disorders, but its value in AHF is unknown. OBJECTIVES: This study sought to determine whether NGAL is superior to creatinine for prediction and/or prognosis of WRF in hospitalized patients with AHF treated with intravenous diuretic agents. METHODS: This was a multicenter, prospective cohort study enrolling patients presenting with AHF requiring intravenous diuretic agents. The primary outcome was whether plasma NGAL could predict the development of WRF, defined as a sustained increase in plasma creatinine of 0.5 mg/dl or >=50% above first value or initiation of acute renal-replacement therapy, within the first 5 days of hospitalization. The main secondary outcome was in-hospital adverse events. RESULTS: We enrolled 927 subjects (mean age, 68.5 years; 62% men). The primary outcome occurred in 72 subjects (7.8%). Peak NGAL was more predictive than the first NGAL, but neither added significant diagnostic utility over the first creatinine (areas under the curve: 0.656, 0.647, and 0.652, respectively). There were 235 adverse events in 144 subjects. The first NGAL was a better predictor than peak NGAL, but similar to the first creatinine (areas under the curve: 0.691, 0.653, and 0.686, respectively). In a post hoc analysis of subjects with an estimated glomerular filtration rate <60 ml/min/1.73 m(2), a first NGAL <150 ng/ml indicated a low likelihood of adverse events. CONCLUSIONS: Plasma NGAL was not superior to creatinine for the prediction of WRF or adverse in-hospital outcomes. The use of plasma NGAL to diagnose acute kidney injury in AHF cannot be recommended at this time. (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin [N-GAL] Evaluation of Symptomatic Heart Failure Study [AKINESIS]; NCT01291836). PMID- 27659465 TI - Plasma NGAL: So, it Really Is Just Expensive Creatinine! PMID- 27659467 TI - Unraveling Myocardial Mass: Using Classical ECG With Contemporary GWAS. PMID- 27659469 TI - Contrast-Induced Acute Kidney Injury. AB - Coronary angiography and percutaneous intervention rely on the use of iodinated intravascular contrast for vessel and chamber imaging. Despite advancements in imaging and interventional techniques, iodinated contrast continues to pose a risk of contrast-induced acute kidney injury (CI-AKI) for a subgroup of patients at risk for this complication. There has been a consistent and graded signal of risk for associated outcomes including need for renal replacement therapy, rehospitalization, and death, according to the incidence and severity of CI-AKI. This paper reviews the epidemiology, pathophysiology, prognosis, and management of CI-AKI as it applies to the cardiac catheterization laboratory. PMID- 27659470 TI - Effect of New Cerebral Ischemic Lesions on the Delirium Occurrence After Transcatheter Aortic Valve Replacement. PMID- 27659468 TI - Atrial Fibrillation and Thromboembolism in Patients With Chronic Kidney Disease. AB - A bidirectional relationship exists between atrial fibrillation (AF) and chronic renal disease. Patients with AF have a higher incidence of renal dysfunction, and the latter predisposes to incident AF. The coexistence of both conditions results in a higher risk for thromboembolic-related adverse events but a paradoxical increased hemorrhagic risk. Oral anticoagulants (both vitamin K antagonists [VKAs] and non-VKA oral anticoagulants [NOACs]) have been demonstrated to be effective in mild to moderate renal dysfunction. Patients with severe renal impairment were excluded from the non-VKA oral anticoagulant trials, so limited data are available. In end-stage renal failure, the net clinical benefit of VKAs in dialysis-dependent patients remains uncertain, although some evidence suggests that such patients may do well with high-quality anticoagulation control. Risk stratification and careful follow-up of such patients are necessary to ensure a net clinical benefit from thromboprophylaxis. PMID- 27659471 TI - Reduction of Ischemic Time for Transferred STEMI Patients Using a Smartphone Social Network System. PMID- 27659472 TI - Endovascular-First Treatment of Peripheral Arterial Disease Remains Controversial. PMID- 27659473 TI - Reply: Endovascular-First Treatment of Peripheral Arterial Disease Remains Controversial. PMID- 27659474 TI - "Catecholamine-Mediated Myocarditis" Versus "Takotsubo Syndrome": What's in a Name? The Lumpers and Splitters Divide. PMID- 27659475 TI - Correction. PMID- 27659466 TI - 52 Genetic Loci Influencing Myocardial Mass. AB - BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 * 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. PMID- 27659476 TI - Expeditious and Divergent Total Syntheses of Aspidosperma Alkaloids Exploiting Iridium(I)-Catalyzed Generation of Reactive Enamine Intermediates. AB - A new approach for the divergent total syntheses of (+/-)-vincaminorine, (+/-)-N methylquebrachamine, (+/-)-quebrachamine, (+/-)-minovine and (+/-) vincadifformine, each in less than 10 linear steps starting from a single delta lactam building block, is reported. Key to our route design is the late-stage generation of reactive enamine functionality from stable indole-linked delta lactams via a highly chemoselective iridium(I)-catalyzed reduction. The efficiently formed secodine intermediates subsequently undergo either a formal Diels-Alder cycloaddition or a competitive Michael addition/reduction to access aspidosperma-type alkaloids in excellent diastereoselectivities. Product selectivity could be controlled by changing the indole N-protecting group in the reductive cyclization precursors. An asymmetric variant of this synthetic strategy for the synthesis of (+)-20-epi-ibophyllidine is also described. PMID- 27659477 TI - T1 mapping in children and young adults with hypertrophic cardiomyopathy. AB - To assess the global and segmental left ventricular (LV) native T1 and extracellular volume fraction (ECV) in children and young adults with hypertrophic cardiomyopathy (HCM) compared to a control cohort. The study population included 21 HCM patients (mean 14.1 +/- 4.6 years) and 21 controls (mean 15.7 +/- 1.5 years). Native modified Look-Locker inversion recovery sequence was performed before and after contrast injection in 3 short axis planes. Global and segmental LV native T1 and ECV were quantified and compared between HCM patients and controls. Mean native T1 in HCM patients and controls was 1020.4 +/- 41.2 and 965.6 +/- 30.2 ms respectively (p < 0.0001). Hypertrophied myocardium had significantly higher native global T1 and global ECV compared to non-hypertrophied myocardium in HCM (p < 0.0001, = 0.14 and 0.048, = 0.01 respectively). In a subset of patients, ECV was higher in LV segments with LGE compared to no LGE (p < 0.0001). No significant correlation was identified between global native T1 and ECV and parameters of LV structure and function. Native T1 cut-off of 987 ms provided the highest sensitivity (95 %) and specificity (91 %) to separate HCM patients from controls. Global and segmental native T1 are elevated in HCM patients. LV segments with hypertrophy and/or LGE had higher ECV in a subset of HCM patients. LV native T1 and ECV do not correlate with parameters of LV structure and function. T1 in children and young adults may be used as a non-invasive tool to assess for HCM and related fibrosis. PMID- 27659479 TI - Effects of high-intensity interval cycling performed after resistance training on muscle strength and hypertrophy. AB - Aim of the study was to investigate whether high-intensity interval cycling performed immediately after resistance training would inhibit muscle strength increase and hypertrophy expected from resistance training per se. Twenty-two young men were assigned into either resistance training (RE; N = 11) or resistance training plus high-intensity interval cycling (REC; N = 11). Lower body muscle strength and rate of force development (RFD), quadriceps cross sectional area (CSA) and vastus lateralis muscle architecture, muscle fiber type composition and capillarization, and estimated aerobic capacity were evaluated before and after 8 weeks of training (2 times per week). Muscle strength and quadriceps CSA were significantly and similarly increased after both interventions. Fiber CSA increased significantly and similarly after both RE (type I: 13.6 +/- 3.7%, type IIA: 17.6 +/- 4.4%, type IIX: 23.2 +/- 5.7%, P < 0.05) and REC (type I: 10.0 +/- 2.7%, type IIA: 14.8 +/- 4.3% type IIX: 20.8 +/- 6.0%, P < 0.05). In contrast, RFD decreased and fascicle angle increased (P < 0.05) only after REC. Capillary density and estimated aerobic capacity increased (P < 0.05) only after REC. These results suggest that high-intensity interval cycling performed after heavy-resistance exercise may not inhibit resistance exercise-induced muscle strength/hypertrophy after 2 months of training, while it prompts aerobic capacity and muscle capillarization. The addition of high intensity cycling after heavy-resistance exercise may decrease RFD partly due to muscle architectural changes. PMID- 27659478 TI - Left ventricular non-compaction and idiopathic dilated cardiomyopathy: the significant diagnostic value of longitudinal strain. AB - Left ventricular non-compaction (LV NC) is characterized by abnormal trabeculations that are mainly at the LV apex. Distinction between LV NC and non specific dilated cardiomyopathies (DCMs) remains often challenging. We sought to find additive tools comparing the longitudinal strain characteristics of LVNC versus idiopathic DCM in a cohort of patients. 48 cases of LVNC (derivation cohort) were compared with 45 cases of DCM. Global and regional multi-layer (sub endocardial, mid-wall, and sub-epicardial) LV longitudinal strain analysis was performed. Results were compared to define the best tool for distinguishing LVNC from DCM. A validation cohort (41 LVNC patients) was then used to assess the performance of the proposed diagnostic tools. In the derivation cohort, longitudinal deformation (strain) was greater in LVNC than in DCM patients. Longitudinal shortening was greater in the non-compacted segments than in the compacted ones. A mid-wall strain base-apex gradient had 88.4 % sensitivity and 66.7 % specificity in distinguishing LVNC from DCM (AUC = 0.83; cut-off of -23 or |0.23|%). In a multivariable model, the base-apex mid-wall gradient in an apical 4-chamber view was the only independent echocardiographic criteria (OR = 0.76, CI 95 % [0.66; 0.90], p = 0.0010) allowing the distinction between LVNC and DCM. In the validation cohort, the base-apex mid-wall gradient of strain had 88.4 % sensitivity, 85.7 % negative predictive values for the diagnosis of LVNC. Longitudinal strain, especially the base-apex longitudinal gradient of strain, appears as an additive valuable tool for distinguishing LVNC from DCM. PMID- 27659480 TI - Test-based age-of-acquisition norms for 44 thousand English word meanings. AB - Age of acquisition (AoA) is an important variable in word recognition research. Up to now, nearly all psychology researchers examining the AoA effect have used ratings obtained from adult participants. An alternative basis for determining AoA is directly testing children's knowledge of word meanings at various ages. In educational research, scholars and teachers have tried to establish the grade at which particular words should be taught by examining the ages at which children know various word meanings. Such a list is available from Dale and O'Rourke's (1981) Living Word Vocabulary for nearly 44 thousand meanings coming from over 31 thousand unique word forms and multiword expressions. The present article relates these test-based AoA estimates to lexical decision times as well as to AoA adult ratings, and reports strong correlations between all of the measures. Therefore, test-based estimates of AoA can be used as an alternative measure. PMID- 27659482 TI - Age and gender effects on bone mass density variation: finite elements simulation. AB - Bone remodeling is a physiological process by which bone constantly adapts its structure to changes in long-term loading manifested by interactions between osteoclasts and osteoblasts. This process can be influenced by many local factors, via effects on bone cells differentiation and proliferation, which are produced by bone cells and act in a paracrine or autocrine way. The aim of the current work is to provide mechanobiological finite elements modeling coupling both cellular activities and mechanical behavior in order to investigate age and gender effects on bone remodeling evolution. A series of computational simulations have been performed on a 2D and 3D human proximal femur. An age- and gender-related impacts on bulk density alteration of trabecular bone have been noticed, and the major actors responsible of this phenomenon have been then discussed. PMID- 27659481 TI - Expression of the aryl hydrocarbon receptor contributes to the establishment of intestinal microbial community structure in mice. AB - Environmental and genetic factors represent key components in the establishment/maintenance of the intestinal microbiota. The aryl hydrocarbon receptor (AHR) is emerging as a pleiotropic factor, modulating pathways beyond its established role as a xenobiotic sensor. The AHR is known to regulate immune surveillance within the intestine through retention of intraepithelial lymphocytes, functional redistribution of Th17/Treg balance. Consequently, environmental/genetic manipulation of AHR activity likely influences host-microbe homeostasis. Utilizing C57BL6/J Ahr-/+ and Ahr-/- co-housed littermates followed by 18 days of genotypic segregation, we examined the influence of AHR expression upon intestinal microbe composition/functionality and host physiology. 16S sequencing/quantitative PCR (qPCR) revealed significant changes in phyla abundance, particularly Verrucomicrobia together with segmented filamentous bacteria, and an increase in species diversity in Ahr-/- mice following genotypic segregation. Metagenomics/metabolomics indicate microbial composition is associated with functional shifts in bacterial metabolism. Analysis identified Ahr-/--dependent increases in ileal gene expression, indicating increased inflammatory tone. Transfer of Ahr-/- microbiota to wild-type germ-free mice recapitulated the increase Verrucomicrobia and inflammatory tone, indicating Ahr /--microbial dependence. These data suggest a role for the AHR in influencing the community structure of the intestinal microbiota. PMID- 27659484 TI - Intercalated water layers promote thermal dissipation at bio-nano interfaces. AB - The increasing interest in developing nanodevices for biophysical and biomedical applications results in concerns about thermal management at interfaces between tissues and electronic devices. However, there is neither sufficient knowledge nor suitable tools for the characterization of thermal properties at interfaces between materials of contrasting mechanics, which are essential for design with reliability. Here we use computational simulations to quantify thermal transfer across the cell membrane-graphene interface. We find that the intercalated water displays a layered order below a critical value of ~1 nm nanoconfinement, mediating the interfacial thermal coupling, and efficiently enhancing the thermal dissipation. We thereafter develop an analytical model to evaluate the critical value for power generation in graphene before significant heat is accumulated to disturb living tissues. These findings may provide a basis for the rational design of wearable and implantable nanodevices in biosensing and thermotherapic treatments where thermal dissipation and transport processes are crucial. PMID- 27659483 TI - The corticospinal tract profile in amyotrophic lateral sclerosis. AB - This work evaluates the potential in diagnostic application of a new advanced neuroimaging method, which delineates the profile of tissue properties along the corticospinal tract (CST) in amyotrophic lateral sclerosis (ALS), by means of diffusion tensor imaging (DTI). Twenty-four ALS patients and twenty-four demographically matched healthy subjects were enrolled in this study. The Automated Fiber Quantification (AFQ), a tool for the automatic reconstruction of white matter tract profiles, based on a deterministic tractography algorithm to automatically identify the CST and quantify its diffusion properties, was used. At a group level, the highest non-overlapping DTI-related differences were detected in the cerebral peduncle, posterior limb of the internal capsule, and primary motor cortex. Fractional anisotropy (FA) decrease and mean diffusivity (MD) and radial diffusivity (RD) increases were detected when comparing ALS patients to controls. The machine learning approach used to assess the clinical utility of this DTI tool revealed that, by combining all DTI metrics measured along tract between the cerebral peduncle and the corona radiata, a mean 5-fold cross validation accuracy of 80% was reached in discriminating ALS from controls. Our study provides a useful new neuroimaging tool to characterize ALS-related neurodegenerative processes by means of CST profile. We demonstrated that specific microstructural changes in the upper part of the brainstem might be considered as a valid biomarker. With further validations this method has the potential to be considered a promising step toward the diagnostic utility of DTI measures in ALS. Hum Brain Mapp 38:727-739, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27659485 TI - Neighborhood Socioeconomic Disadvantage; Neighborhood Racial Composition; and Hypertension Stage, Awareness, and Treatment Among Hypertensive Black Men in New York City: Does Nativity Matter? AB - OBJECTIVE: Neighborhood-level poverty and racial composition may contribute to racial disparities in hypertension outcomes. Little is known about how the effects of neighborhood social environments may differ by nativity status among diverse urban Black adults. We aimed to characterize the influence of neighborhood-level socio-demographic factors on hypertension outcomes among US- and foreign-born Black men with uncontrolled blood pressure. DESIGN: We conducted a cross-sectional analysis of baseline data from two large community-based trials of hypertensive Black men aged 50 and over linked with census tract data from the 2012 American Community Survey 5-year estimates. We defined census tracts with high racial segregation as those where 60 % or more self-identified as Black and high-poverty census tracts as those where 20 % or more lived below the poverty line. Multivariable general estimating equation models were used to measure associations between neighborhood characteristics and stage of hypertension, hypertension awareness, and treatment to yield adjusted prevalence ratios (aPR). Models were run separately for US- and foreign-born Black men. RESULTS: Over 64 % of the 1139 participants lived in a census tract with a high percentage of Black residents and over 71 % lived in high-poverty census tracts. Foreign-born Black men living in neighborhoods with a high concentration of Black residents were less likely to be treated for their high blood pressure (aPR 0.44, 95 % CI 0.22 0.88), but this result did not hold for US-born Black men. There were no significant associations between neighborhood poverty and hypertension outcomes. CONCLUSIONS: Neighborhood context may impact treatment for hypertension, one of the most important factors in hypertension control and decreasing hypertension related mortality, particularly among foreign-born Black men. PMID- 27659486 TI - Modeling the Effects of Sensorineural Hearing Loss on Sound Localization in the Median Plane. AB - Listeners use monaural spectral cues to localize sound sources in sagittal planes (along the up-down and front-back directions). How sensorineural hearing loss affects the salience of monaural spectral cues is unclear. To simulate the effects of outer-hair-cell (OHC) dysfunction and the contribution of different auditory-nerve fiber types on localization performance, we incorporated a nonlinear model of the auditory periphery into a model of sagittal-plane sound localization for normal-hearing listeners. The localization model was first evaluated in its ability to predict the effects of spectral cue modifications for normal-hearing listeners. Then, we used it to simulate various degrees of OHC dysfunction applied to different types of auditory-nerve fibers. Predicted localization performance was hardly affected by mild OHC dysfunction but was strongly degraded in conditions involving severe and complete OHC dysfunction. These predictions resemble the usually observed degradation in localization performance induced by sensorineural hearing loss. Predicted localization performance was best when preserving fibers with medium spontaneous rates, which is particularly important in view of noise-induced hearing loss associated with degeneration of this fiber type. On average across listeners, predicted localization performance was strongly related to level discrimination sensitivity of auditory-nerve fibers, indicating an essential role of this coding property for localization accuracy in sagittal planes. PMID- 27659487 TI - Perception of Interaural Phase Differences With Envelope and Fine Structure Coding Strategies in Bilateral Cochlear Implant Users. AB - The ability to detect a target signal masked by noise is improved in normal hearing listeners when interaural phase differences (IPDs) between the ear signals exist either in the masker or in the signal. To improve binaural hearing in bilaterally implanted cochlear implant (BiCI) users, a coding strategy providing the best possible access to IPD is highly desirable. In this study, we compared two coding strategies in BiCI users provided with CI systems from MED-EL (Innsbruck, Austria). The CI systems were bilaterally programmed either with the fine structure processing strategy FS4 or with the constant rate strategy high definition continuous interleaved sampling (HDCIS). Familiarization periods between 6 and 12 weeks were considered. The effect of IPD was measured in two types of experiments: (a) IPD detection thresholds with tonal signals addressing mainly one apical interaural electrode pair and (b) with speech in noise in terms of binaural speech intelligibility level differences (BILD) addressing multiple electrodes bilaterally. The results in (a) showed improved IPD detection thresholds with FS4 compared with HDCIS in four out of the seven BiCI users. In contrast, 12 BiCI users in (b) showed similar BILD with FS4 (0.6 +/- 1.9 dB) and HDCIS (0.5 +/- 2.0 dB). However, no correlation between results in (a) and (b) both obtained with FS4 was found. In conclusion, the degree of IPD sensitivity determined on an apical interaural electrode pair was not an indicator for BILD based on bilateral multielectrode stimulation. PMID- 27659488 TI - Liprin-alpha1 and ERC1 control cell edge dynamics by promoting focal adhesion turnover. AB - Liprin-alpha1 and ERC1 are interacting scaffold proteins regulating the motility of normal and tumor cells. They act as part of plasma membrane-associated platforms at the edge of motile cells to promote protrusion by largely unknown mechanisms. Here we identify an amino-terminal region of the liprin-alpha1 protein (liprin-N) that is sufficient and necessary for the interaction with other liprin-alpha1 molecules. Similar to liprin-alpha1 or ERC1 silencing, expression of the liprin-N negatively affects tumor cell motility and extracellular matrix invasion, acting as a dominant negative by interacting with endogenous liprin-alpha1 and causing the displacement of the endogenous ERC1 protein from the cell edge. Interfering with the localization of ERC1 at the cell edge inhibits the disassembly of focal adhesions, impairing protrusion. Liprin alpha1 and ERC1 proteins colocalize with active integrin beta1 clusters distinct from those colocalizing with cytoplasmic focal adhesion proteins, and influence the localization of peripheral Rab7-positive endosomes. We propose that liprin alpha1 and ERC1 promote protrusion by displacing cytoplasmic adhesion components to favour active integrin internalization into Rab7-positive endosomes. PMID- 27659489 TI - Commentary on tumor heterogeneity. PMID- 27659490 TI - Intergenerational Trauma in Refugee Families: A Systematic Review. AB - Although a robust literature describes the intergenerational effects of traumatic experiences in various populations, evidence specific to refugee families is scattered and contains wide variations in approaches for examining intergenerational trauma. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, the purpose of this systematic review was to describe the methodologies and findings of peer-reviewed literature regarding intergenerational trauma in refugee families. In doing so we aimed to critically examine how existing literature characterizes refugee trauma, its long term effects on descendants, and psychosocial processes of transmission in order to provide recommendations for future research. The results highlight populations upon which current evidence is based, conceptualizations of refugee trauma, effects of parental trauma transmission on descendants' health and well-being, and mechanisms of transmission and underlying meanings attributed to parental trauma in refugee families. Greater methodological rigor and consistency in future evidence-based research is needed to inform supportive systems that promote the health and well-being of refugees and their descendants. PMID- 27659491 TI - Low accumulation of chlorogenic acids represses reddening during flesh browning in Japanese peach "Okayama PEH7". AB - In peaches, fruit flesh browns unattractively after peeling or cutting. A recently developed cultivar, Okayama PEH7, was distinct from other Japanese cultivars, including Okayama PEH8, with respect to its reduced browning potential. Homogenate prepared from Okayama PEH7 flesh had significantly less reddening during the browning reaction. Okayama PEH7 had less soluble phenolic compounds and higher polyphenol oxidase activity than Okayama PEH8. Reduced browning was observed even when phenols prepared from Okayama PEH7 were incubated with crude extract from Okayama PEH8, suggesting that phenols lower the browning potential of Okayama PEH7. In Okayama PEH7, contents of chlorogenic acid and its isomers were about one-tenth compared to Okayama PEH8. Exogenous addition of chlorogenic acid to Okayama PEH7 homogenate increased the browning potential and visibly enhanced reddening. These results indicate that the reduced browning of Okayama PEH7 flesh is due to a defect in chlorogenic acid accumulation. PMID- 27659493 TI - Identification of putative chemosensory receptor genes from yellow peach moth Conogethes punctiferalis (Guenee) antennae transcriptome. AB - The yellow peach moth, Conogethes punctiferalis, is an extremely important polyphagous insect in Asia. The chemosensory systems of moth play an important role in detecting food, oviposition sites and mate attraction. Several antennal chemosensory receptors are involved in odor detection. Our study aims to identify chemosensory receptor genes for potential applications in behavioral responses of yellow peach moth. By transcriptomic analysis of male and female antennae, 83 candidate chemosensory receptors, including 62 odorant receptors, 11 ionotropic receptors and 10 gustatory receptors were identified. Through Blast and sequence alignment, the highly conserved co-receptor Orco was annotated, eight unigenes clustered into pheromone receptors, and two clustered as sugar receptor. Among the IRs, one unigenes was similar with co-receptors IR25a. Expression levels of 50 odorant receptors were further evaluated by quantitative real-time PCR in antennae. All the ORs tested were detected in antennae and some of which were associated with sex-biased expression. The chemosensory receptors identified in C. punctiferalis provide a foundational resource for further analysis on olfaction for behavior. The expression profiles of ORs in antennae indicated variant functions in olfactory recognition, and our results provided the possibility for the potential application of semiochemical to control this pest moth. PMID- 27659494 TI - SENP1 Is a Crucial Regulator for Cell Senescence through DeSUMOylation of Bmi1. AB - Cell senescence can limit proliferative potential and prevent tumorigenesis. Bmi1 is a key regulator in cell senescence by suppressing the Ink4a/Arf locus. However, how to regulate Bmi1 activity in cell senescence is largely unknown. Here, we show that SENP1 plays an important role in cell senescence by regulating Bmi1 SUMOylation. Senp1-/- primary MEF cells show resistance to cell senescence induced by passaging or other senescence inducing signals. SENP1 deficiency also reduces oncogene H-RasV12-induced senescence, and enhances H-RasV12-induced cell transformation. We further show that in Senp1-/- MEFs the expression of p19Arf, an important regulator in p53/p21-mediated cell senescence, is markedly reduced. Meanwhile, we demonstrate that SENP1 can specifically de-SUMOylate Bmi1 and thereby decreases the occupancy of Bmi1 on p19Arf promoter leading to decrease of H2AK119 mono-ubiquitination and up-expression of p19Arf. These data reveal a crucial role of SENP1 in regulation of cell senescence as well as cell transformation. PMID- 27659492 TI - CB1 receptor activation in the rat paraventricular nucleus induces bi-directional cardiovascular effects via modification of glutamatergic and GABAergic neurotransmission. AB - We have shown previously that the cannabinoid receptor agonist CP55940 microinjected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anaesthetized rats induces depressor and pressor cardiovascular effects in the absence and presence of the CB1 antagonist AM251, respectively. The aim of our study was to examine whether the hypotension and/or hypertension induced by CP55940 given into the PVN results from its influence on glutamatergic and GABAergic neurotransmission. CP55940 was microinjected into the PVN of urethane anaesthetized rats twice (S1 and S2, 20 min apart). Antagonists of the following receptors, NMDA (MK801), beta2-adrenergic (ICI118551), thromboxane A2-TP (SQ29548), angiotensin II-AT1 (losartan) or GABAA (bicuculline), or the NO synthase inhibitor L-NAME were administered intravenously 5 min before S2 alone or together with AM251. The CP55940-induced hypotension was reversed into a pressor response by AM251, bicuculline and L-NAME, but not by the other antagonists. The CP55940-induced pressor effect examined in the presence of AM251 was completely reversed by losartan, reduced by about 50-60 % by MK801, ICI118551 and SQ29548, prevented by bilateral adrenalectomy but not modified by bicuculline and L-NAME. Parallel, but smaller, changes in heart rate accompanied the changes in blood pressure. The bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids microinjected into the PVN of anaesthetized rats depend on stimulatory glutamatergic and inhibitory GABAergic inputs to the sympathetic tone; the glutamatergic input is related to AT1, TP and beta2-adrenergic receptors and catecholamine release from the adrenal medulla whereas the GABAergic input is reinforced by NO. PMID- 27659496 TI - A 2D virtual reality system for visual goal-driven navigation in zebrafish larvae. AB - Animals continuously rely on sensory feedback to adjust motor commands. In order to study the role of visual feedback in goal-driven navigation, we developed a 2D visual virtual reality system for zebrafish larvae. The visual feedback can be set to be similar to what the animal experiences in natural conditions. Alternatively, modification of the visual feedback can be used to study how the brain adapts to perturbations. For this purpose, we first generated a library of free-swimming behaviors from which we learned the relationship between the trajectory of the larva and the shape of its tail. Then, we used this technique to infer the intended displacements of head-fixed larvae, and updated the visual environment accordingly. Under these conditions, larvae were capable of aligning and swimming in the direction of a whole-field moving stimulus and produced the fine changes in orientation and position required to capture virtual prey. We demonstrate the sensitivity of larvae to visual feedback by updating the visual world in real-time or only at the end of the discrete swimming episodes. This visual feedback perturbation caused impaired performance of prey-capture behavior, suggesting that larvae rely on continuous visual feedback during swimming. PMID- 27659495 TI - Interaction between Cucumber mosaic virus 2b protein and plant catalase induces a specific necrosis in association with proteasome activity. AB - KEY MESSAGE: Cucumber mosaic virus (CMV) can induce a specific necrosis on Arabidopsis through the interaction between the CMV 2b protein and host catalase, in which the ubiquitin-proteasome pathway may be involved. We previously reported that the CMV 2b protein, the viral RNA silencing suppressor, interacted with the H2O2 scavenger catalase (CAT3), leading to necrosis on CMV-inoculated Arabidopsis leaves. We here confirmed that CMV could more abundantly accumulate in the CAT3 knockout mutant (cat3), and that CAT3 makes host plants a little more tolerant to CMV. We also found that the necrosis severity is not simply explained by a high level of H2O2 given by the lack of CAT3, because the recombinant CMV, CMV-N, induced much milder necrosis in cat3 than in the wild type, suggesting some specific mechanism for the necrosis induction. To further characterize the 2b inducing necrosis in relation to its binding to CAT3, we conducted the agroinfiltration experiments to overexpress CAT3 and 2b in N. benthamiana leaves. The accumulation levels of CAT3 were higher when co-expressed with the CMV-N 2b (N2b) than with CMV-Y 2b (Y2b). We infer that N2b made a more stable complex with CAT3 than Y2b did, and the longevity of the 2b-CAT3 complex seemed to be important to induce necrosis. By immunoprecipitation (IP) with an anti-ubiquitin antibody followed by the detection with anti-CAT3 antibodies, we detected a higher molecular-weight smear and several breakdown products of CAT3 among the IP proteins. In addition, the proteasome inhibitor MG132 treatment could actually increase the accumulation levels of CAT3. This study suggests that the host proteasome pathway is, at least partially, responsible for the degradation of CAT3, which is manifested in CMV-infected tissues. PMID- 27659497 TI - 2D Hexagonal Boron Nitride (2D-hBN) Explored for the Electrochemical Sensing of Dopamine. AB - Crystalline 2D hexagonal boron nitride (2D-hBN) nanosheets are explored as a potential electrocatalyst toward the electroanalytical sensing of dopamine (DA). The 2D-hBN nanosheets are electrically wired via a drop-casting modification process onto a range of commercially available carbon supporting electrodes, including glassy carbon (GC), boron-doped diamond (BDD), and screen-printed graphitic electrodes (SPEs). 2D-hBN has not previously been explored toward the electrochemical detection/electrochemical sensing of DA. We critically evaluate the potential electrocatalytic performance of 2D-hBN modified electrodes, the effect of supporting carbon electrode platforms, and the effect of "mass coverage" (which is commonly neglected in the 2D material literature) toward the detection of DA. The response of 2D-hBN modified electrodes is found to be largely dependent upon the interaction between 2D-hBN and the underlying supporting electrode material. For example, in the case of SPEs, modification with 2D-hBN (324 ng) improves the electrochemical response, decreasing the electrochemical oxidation potential of DA by ~90 mV compared to an unmodified SPE. Conversely, modification of a GC electrode with 2D-hBN (324 ng) resulted in an increased oxidation potential of DA by ~80 mV when compared to the unmodified electrode. We explore the underlying mechanisms of the aforementioned examples and infer that electrode surface interactions and roughness factors are critical considerations. 2D-hBN is utilized toward the sensing of DA in the presence of the common interferents ascorbic acid (AA) and uric acid (UA). 2D-hBN is found to be an effective electrocatalyst in the simultaneous detection of DA and UA at both pH 5.0 and 7.4. The peak separations/resolution between DA and UA increases by ~70 and 50 mV (at pH 5.0 and 7.4, respectively, when utilizing 108 ng of 2D hBN) compared to unmodified SPEs, with a particularly favorable response evident in pH 5.0, giving rise to a significant increase in the peak current of DA. The limit of detection (3sigma) is found to correspond to 0.65 MUM for DA in the presence of UA. However, it is not possible to deconvolute the simultaneous detection of DA and AA. The observed electrocatalytic effect at 2D-hBN has not previously been reported in the literature when supported upon carbon or any other electrode. We provide valuable insights into the modifier-substrate interactions of this material, essential for those designing, fabricating, and consequently performing electrochemical experiments utilizing 2D-hBN and related 2D materials. PMID- 27659498 TI - Sialendoscopy under local anaesthesia. AB - CONCLUSIONS: In most cases, both diagnostic and interventional sialendoscopy are well tolerated under local anaesthesia (LA) or under local anaesthesia with sedation (LAS), with reasonably low patient-reported discomfort. Sialendoscopy can be considered a patient-friendly and relatively painless, gland-preserving, minimally invasive procedure suitable for day surgery. OBJECTIVE: To investigate patient experience and compliance in sialendoscopy under LA/LAS. METHODS: This prospective study was conducted at an academic tertiary-care university hospital. During a period of 22 months, 89 patients between ages 16-81 years underwent diagnostic or interventional sialendoscopy under LA (20%) or LAS (80%). After the operation the patients filled in a questionnaire formulated by the authors concerning their procedure-related experiences. Patients' demographic data, ASA status score, pre- and intra-operative blood pressure and heart rate measurements, affected gland, operation time, intervention type, as well as pre-, peri-, and postoperative medication were gathered later from the medical records. RESULTS: The level of discomfort and pain experienced during the operation was assessed as 'mild' or 'none' by 85% and 89% of the patients, respectively. The level of pain experienced after the operation was 'major' in 4% of patients and 'mild' or 'none' in the majority (87%) of patients. The patients' estimations showed no significant difference between the diagnostic and interventional procedures, although it seems that patients who underwent stone removal by transoral incision experienced the operation as a bit more uncomfortable and painful than other patients. Afterwards 97% of patients stated that they would agree to a new LA/LAS sialendoscopy in the future if needed. PMID- 27659499 TI - The effect of previous experience on trap construction and movement distance in a pit-building predator. AB - Wormlion larvae are sit-and-wait predators that construct cone-shaped pits in sandy patches to capture prey. Wormlions select microhabitats that feature favorable conditions for pit construction, in a similar way to other trap building predators, like spiders and antlions. We investigated whether wormlions exhibit an experience-based behavioral plasticity in their pit construction behavior. In a laboratory experiment, pit sizes and relocation distances were compared between larvae that experienced either a period of unfavorable conditions, i.e., surface obstacles, shallow or coarse sand, or a period of favorable conditions, i.e., clear, deep, and fine sand and were able to construct pits undisturbed. We expected that wormlions experiencing improving conditions would build larger pits than those experiencing deteriorating conditions. In addition, we expected that larvae experiencing unfavorable conditions would be less choosy in their new microhabitat and move over shorter distances. We observed a certain effect of recent experience on the trap-building behavior; however, it was not consistent among treatments. Additionally, we detected a correlation between larval body mass, relocation distance, and pit area. These findings might suggest that past experience does not influence wormlion foraging behavior in a simple manner but that different types of experience induce different behavioral responses. PMID- 27659500 TI - Cardiac t-tubules: where structural plasticity meets functional adaptation. PMID- 27659502 TI - Corrigendum. PMID- 27659501 TI - Conflicting mechanisms of AT2 cardioprotection revealed. PMID- 27659503 TI - Effects of fixed and removable space maintainers on halitosis. AB - BACKGROUND: The current study evaluated the effects of fixed and removable space maintainers on halitosis and oral health of children. METHODS: Forty-three patients randomly selected between the ages 4-10 whom fixed or removable space maintainers were indicated in Gazi University, Faculty of Dentistry, Department of Pedodontics. The inclusing criteria were: caries-free (with/without restorations), with absence of periodontal diseases, without systematic disease, no mouth breathing and no use of antibiotics the 2-months period before the study. The patients were subdivided into two groups: the group treated with fixed space maintainers (group 1, n = 27), the group treated with removable space maintainers (group 2, n = 16). The the plaque index (PI), gingival index (GI), periodontal screening index (PSI), tongue coating index (TCI) records and the halitosis measurements were obtained at three time periods (T1: immediately after application, T2: 1 week after application, T3: 5 weeks after application). The measurement values of T1 served as control. RESULTS: No statistically significant difference was found in the PI, GI, PSI, TCI and halitosis measurements between T1-T2, T2-T3 and T1-T3 in both appliance groups and between the groups (p > 0.05). CONCLUSIONS: The fixed and removable space maintainers did not affect oral health status and halitosis significantly. PMID- 27659504 TI - Impact of non-steroidal anti-inflammatory drugs on cardiovascular risk: Is it the same in osteoarthritis and rheumatoid arthritis? AB - Although large-scale population studies have shown that non-steroidal anti inflammatory drugs (NSAIDs) increase the risk of myocardial infarction, this is not confirmed in patients with rheumatoid arthritis (RA). Herein, we review the litterature on the differential effects of NSAIDs on cardiovascular risk in osteoarthritis (OA) versus RA and discuss possible explanations for this discrepancy. To assess a potential additive effect of age in non-RA populations, we compared weighted mean age between RA patients and unselected NSAID users included in cohort and case-control studies that estimate the cardiovascular risk of NSAIDs, assuming that the main indication for NSAID usage in elderly populations is OA. Our hypothesis that advanced age in osteoarthtitis compared to RA patients confounds the effect of NSAIDs on cardiovasular risk was not confirmed. Several other hypotheses that can be proposed to explain this counterintuitive effect of NSAIDs on the cardiovascular risk of RA patients are discussed. We conclude that patients with RA have a lower cardiovascular disease risk associated with the use of NSAIDs, probably due to the nature of their disease per se, until further research indicates differently. PMID- 27659505 TI - Distance measurements in peridinin-chlorophyll a-protein by light-induced PELDOR spectroscopy. Analysis of triplet state localization. AB - Triplet-triplet energy transfer from chlorophylls to carotenoids is the mechanism underlying the photoprotective role played by carotenoids in many light harvesting complexes, during photosynthesis. The peridinin-chlorophyll-a protein (PCP) is a water-soluble light harvesting protein of the dinoflagellate Amphidinium carterae, employing peridinin as the main carotenoid to fulfil this function. The dipolar coupling of the triplet state of peridinin, populated under light excitation in isolated PCP, to the MTSSL nitroxide, introduced in the protein by site-directed mutagenesis followed by spin labeling, has been measured by Pulse ELectron-electron DOuble Resonance (PELDOR) spectroscopy. The triplet nitroxide distance derived by this kind of experiments, performed for the first time in a protein system, allowed the assignment of the triplet state to a specific peridinin molecule belonging to the pigment cluster. The analysis strongly suggests that this peridinin is the one in close contact with the water ligand to the chlorophyll a, thus supporting previous evidences based on ENDOR and time resolved-EPR. PMID- 27659506 TI - Photochemical characterization of actinorhodopsin and its functional existence in the natural host. AB - Actinorhodopsin (ActR) is a light-driven outward H+ pump. Although the genes of ActRs are widely spread among freshwater bacterioplankton, there are no prior data on their functional expression in native cell membranes. Here, we demonstrate ActR phototrophy in the native actinobacterium. Genome analysis showed that Candidatus Rhodoluna planktonica, a freshwater actinobacterium, encodes one microbial rhodopsin (RpActR) belonging to the ActR family. Reflecting the functional expression of RpActR, illumination induced the acidification of the actinobacterial cell suspension and then elevated the ATP content inside the cells. The photochemistry of RpActR was also examined using heterologously expressed RpActR in Escherichia coli membranes. The purified RpActR showed lambdamax at 534nm and underwent a photocycle characterized by the very fast formation of M intermediate. The subsequent intermediate, named P620, could be assigned to the O intermediate in other H+ pumps. In contrast to conventional O, the accumulation of P620 remains prominent, even at high pH. Flash-induced absorbance changes suggested that there exists only one kind of photocycle at any pH. However, above pH7, RpActR shows heterogeneity in the H+ transfer sequences: one first captures H+ and then releases it during the formation and decay of P620, while the other first releases H+ prior to H+ uptake during P620 formation. PMID- 27659509 TI - Testosterone supplementation for "low T" is not supported by evidence, review concludes. PMID- 27659507 TI - Rapid urine-based screening for tuberculosis to reduce AIDS-related mortality in hospitalized patients in Africa (the STAMP trial): study protocol for a randomised controlled trial. AB - BACKGROUND: HIV-associated tuberculosis (TB) co-infection remains an enormous burden to international public health. Post-mortem studies have highlighted the high proportion of HIV-positive adults admitted to hospital with TB. Determine TB LAM and Xpert MTB/RIF assays can substantially increase diagnostic yield of TB within one day of hospital admission. However, it remains unclear if this approach can impact clinical outcomes. The STAMP trial aims to test the hypothesis that the implementation a urine-based screening strategy for TB can reduce all cause-mortality among HIV-positive patients admitted to hospital when compared to current, sputum-based screening. METHODS: The trial is a pragmatic, individually randomised, multi-country (Malawi and South Africa) clinical trial with two study arms (1:1 recruitment). Unselected HIV-positive patients admitted to medical wards, irrespective of presentation, meeting the inclusion criteria and giving consent will be randomized to screening for TB using either: (i) 'standard of care'- testing of sputum using the Xpert MTB/RIF assay (Xpert) or (ii) 'intervention'- testing of sputum using Xpert and testing of urine using (a) Determine TB-LAM lateral-flow assay and (b) Xpert following concentration of urine by centrifugation. Patients will be excluded if they have received TB treatment in the previous 12 months, if they have received isoniazid preventive therapy in the last 6 months, if they are aged <18 years or they live outside the pre-specified geographical area. Results will be provided to the responsible medical team as soon as available to inform decisions regarding TB treatment. Both the study and routine medical team will be masked to study arm allocation. 1300 patients will be enrolled per arm (equal numbers at the two trial sites). The primary endpoint is all-cause mortality at 56 days. An economic analysis will be conducted to project long-term outcomes for shorter-term trial data, including cost-effectiveness. DISCUSSION: This pragmatic trial assesses an intervention to reduce the high mortality caused by HIV-associated TB, which could feasibly be scaled up in high-burden settings if shown to be efficacious and cost-effective. We discuss the challenges of designing a trial to assess the impact on mortality of laboratory-based TB screening interventions given frequent initiation of empirical treatment and a failure of several previous clinical trials to demonstrate an impact on clinical outcomes. We also elaborate on the practical and ethical issues of 'testing a test' in general. TRIAL REGISTRATION: ISRCTN Registry ( ISRCTN71603869 ) prospectively registered 08 May 2015; the South African National Controlled Trials Registry (DOH-27-1015-5185) prospectively registered October 2015. PMID- 27659508 TI - Consultant outcomes publication and surgical training: Consensus recommendations by the association of surgeons in training. AB - Consultant Outcomes Publication (COP) has the longest history in cardiothoracic surgery, where it was introduced in 2005. Subsequently COP has been broadened to include all surgical specialties in NHS England in 2013-14. The Association of Surgeons in Training (ASiT) fully supports efforts to improve patient care and trust in the profession and is keen to overcome potential unintended adverse effects of COP. Identification of these adverse effects is the first step in this process: Firstly, there is a risk that COP may lead to reluctance by consultants to provide trainees with the necessary appropriate primary operator experience to become skilled consultant surgeons for the future. Secondly, COP may lead to inappropriately cautious case selection. This adjusted case mix affects both patients who are denied operations, and also limits the complexity of the case mix to which surgical trainees are exposed. Thirdly, COP undermines efforts to train surgical trainees in non-technical skills and human factors, simply obliterating the critical role of the multidisciplinary team and organisational processes in determining outcomes. This tunnel vision masks opportunities to improve patient care and outcomes at a unit level. It also misinforms the public as to the root causes of adverse events by failing to identify care process deficiencies. Finally, for safe surgical care, graduate retention and morale is important - COP may lead to high calibre trainees opting out of surgical careers, or opting to work abroad. The negative effects of COP on surgical training and trainees must be addressed as high quality surgical training and retention of high calibre graduates is essential for excellent patient care. PMID- 27659510 TI - Choline-magnesium trisalicylate modulates acute myelogenous leukemia gene expression during induction chemotherapy. PMID- 27659512 TI - mTOR inhibitors in pancreas transplant: adverse effects and drug-drug interactions. AB - INTRODUCTION: Patient and pancreas allograft survival improved following reductions in surgical complications, tighter donor selection and optimization in immunosuppressive protocols. However, long-term survival of pancreas allografts is adversely affected by rejection and immunosuppressive regimen toxicity. Areas covered: This article reviews the existing literature and knowledge of mammalian target of rapamycin inhibitors (mTORi). Some clinically relevant drug-drug interactions are highlighted. We summarize the nephrotoxic and diabetogenic mechanisms of mTORi after pancreas transplant, the alternatives to minimize these effects, and report on other adverse events. Expert opinion: Calcineurin inhibitor (CNI)-based regimens remain the mainstay treatment after pancreas kidney transplant. However, long-term use of CNIs may be associated with nephrotoxicity. Switching from CNIs to mTORi (sirolimus/SRL and everolimus/EVR) may preserve kidney function, mainly EVR conversion. However, mTORi promote an imbalance of mTOR signaling during long-term follow-up and may ultimately contribute to proteinuria and hyperglycemia. These drugs disrupt autophagy, inhibit cell proliferation, and downregulate VEGF. Therefore, it is important to comprehend and interpret the experimental data. It is equally important to critically analyze clinical studies. Of importance, minimization of side effects, based on safe approaches, can prolong kidney allograft survival. Additional randomized-controlled studies are required to assess the impact of mTORi on pancreas allograft survival. PMID- 27659511 TI - Protocol for the systematic review of the prevention, treatment and public health management of impetigo, scabies and fungal skin infections in resource-limited settings. AB - BACKGROUND: Impetigo, scabies, and fungal skin infections disproportionately affect populations in resource-limited settings. Evidence for standard treatment of skin infections predominantly stem from hospital-based studies in high-income countries. The evidence for treatment in resource-limited settings is less clear, as studies in these populations may lack randomisation and control groups for cultural, ethical or economic reasons. Likewise, a synthesis of the evidence for public health control within endemic populations is also lacking. We propose a systematic review of the evidence for the prevention, treatment and public health management of skin infections in resource-limited settings, to inform the development of guidelines for the standardised and streamlined clinical and public health management of skin infections in endemic populations. METHODS: The protocol has been designed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. All trial designs and analytical observational study designs will be eligible for inclusion. A systematic search of the peer-reviewed literature will include PubMed, Excertpa Medica and Global Health. Grey literature databases will also be systematically searched, and clinical trials registries scanned for future relevant studies. The primary outcome of interest will be the clinical cure or decrease in prevalence of impetigo, scabies, crusted scabies, tinea capitis, tinea corporis or tinea unguium. Two independent reviewers will perform eligibility assessment and data extraction using standardised electronic forms. Risk of bias assessment will be undertaken by two independent reviewers according to the Cochrane Risk of Bias tool. Data will be tabulated and narratively synthesised. We expect there will be insufficient data to conduct meta-analysis. The final body of evidence will be reported against the Grades of Recommendation, Assessment, Development and Evaluation grading system. DISCUSSION: The evidence derived from the systematic review will be used to inform the development of guidelines for the management of skin infections in resource-limited settings. The evidence derived will be intended for use by clinicians, public health practitioners and policy makers in the treatment of skin infections and the development of skin infection control programmes. The review will identify any gaps in the current evidence to provide direction for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029453. PMID- 27659513 TI - Suicidal Behaviors Among Adolescents - The Role of School and Home Environment. AB - AIM: This study aimed to determine the prevalence of suicidal behaviors (ideation, planning, and attempts) among adolescents aged 13-16, and to identify psychosocial correlates of suicidal behaviors. METHOD: The 2010 Kuwait Global School-Based Student Health Survey (GSHS) cross-sectional study employed a two stage cluster sample design targeting a representative sample of 2,672 students. A weighting factor was applied to make inferences to all students of the same age. Students' suicidal behaviors were the focus of this paper. RESULTS: The prevalence rates of suicide ideation, planning, and attempts were 20.0% (95% CI = 18.5-21.6%), 14.0% (95% CI = 12.7-15.4%), and 18.1% (95% CI = 16.6-19.5%), respectively. About 26% of adolescents reported at least one suicidal behavior, while 8.5% experienced all three suicidal behaviors. Multivariate analysis revealed that girls, smoking, physical violence, feeling lonely, exposure to bullying at school, and having nonempathetic parents were significant correlates of the experience of suicidal behaviors among adolescents. Moreover, suicidal ideation stood out as a predictor of attempting suicide more than suicidal planning in both the total population and separately by gender. CONCLUSION: The prevalence of suicidal behaviors was alarmingly high among Kuwaiti adolescents. Adverse school and home environments strongly contributed to such behaviors. School-based mental health programs are necessary to reduce these life threatening behaviors in Kuwait. PMID- 27659515 TI - Factors Related to Suicide in LGBT Populations. AB - BACKGROUND: There is evidence of heightened vulnerability to nonfatal suicidal behaviors among LGBT populations yet a paucity of studies into fatal behaviors. AIM: The specific aim of this article was to identify factors related to suicide in LGBT individuals in Australia. METHOD: The psychological autopsy (PA) method with a matched case-control study design was used. PA interviews were conducted with 27 next-of-kin of an LGBT person that had died by suicide. Three living LGBT controls per suicide case, matched by age and gender, were also interviewed. RESULTS: The key factors relating to suicide in LGBT people were a lack of acceptance by family and self (reflected in higher internalized homophobia and shame), negative feelings about own sexuality/gender, and dissatisfaction with appearance. LGBT people who died by suicide also tended to go through coming out milestones 2 years earlier than controls. There was a higher prevalence of aggressive behaviors and a more predominant history of physical and sexual abuse. Additionally, there was greater incidence of depression and anxiety and alcohol and substance use disorders. CONCLUSION: Specific predictive factors for suicide in LGBT populations in Australia were identified, including significantly poorer mental health outcomes and more violence across an array of measures. PMID- 27659516 TI - Comprehensive Online Self-Monitoring to Support Clinicians Manage Risk of Suicide in Youth Depression. AB - BACKGROUND: Routine monitoring of depression symptoms and suicide risk is essential for appropriate treatment planning and risk management, but not well implemented by clinicians. We developed a brief online monitoring tool to address this issue. AIMS: To investigate whether the online tool can feasibly improve monitoring; whether it is acceptable and useful for young people and their clinicians; and to determine whether a shorter tool could be implemented. METHOD: In a naturalistic longitudinal cohort study, 101 young people with depression completed the online tool on a tablet, prior to their consultation. Their results were immediately available to their clinician. Clients and clinicians answered questionnaires about acceptability and usefulness. RESULTS: The tool was feasible to implement. Young people and clinicians found the tool acceptable and useful for understanding symptoms and risk. A brief three-item suicidal ideation screening measure correlated well with a validated measure of suicidal ideation. CONCLUSION: The online tool facilitates the quick exchange of key information about suicide risk, allowing clinicians to immediately address this. This level of responsiveness is likely to improve treatment outcomes. The brief version allows full integration into clinical practice to support clinicians managing those at risk of suicide. PMID- 27659517 TI - Online Suicide Risk Assessment and Management Training. AB - BACKGROUND: Many mental health professionals (MHPs) encounter youth at risk for suicide but lack knowledge and confidence to assist these individuals. Unfortunately, training for MHPs on suicide risk assessment and management is often not adequately accessible. AIMS: The aim of this study was to evaluate whether MHPs' knowledge, attitudes, perceived social norms, and perceived behavioral control in working with at-risk suicidal youth improve following an online training (QPRT: Question, Persuade, Refer, Treat). METHOD: QPRT was provided to 225 MHPs from three large urban areas in the United States. Suicide prevention literacy, attitudes, perceived social norms, and perceived behavioral control in assessing and managing suicide risk were assessed before and after training. Data were also collected on training engagement and completion. RESULTS: Suicide prevention literacy in most competency domains and perceived behavioral control increased significantly after participation in QPRT. Suicide prevention attitudes and some knowledge domains did not significantly improve. MHPs reported high satisfaction with the training. CONCLUSION: The current study provides initial support for offering MHPs online suicide risk assessment and management training. Online training programs may be an engaging and feasible means for providing advanced suicide prevention skills to MHPs who may have numerous barriers to accessing face-to-face training. PMID- 27659518 TI - Positive parenting for healthy living (Triple P) for parents of children with type 1 diabetes: protocol of a randomised controlled trial. AB - BACKGROUND: Type 1 diabetes is a serious, life-long condition which causes major health, social and economic burden for children, their families and the community. Diabetes management involves strict adherence to a complex regimen, and poor management and non-adherence are a persistent problem among children. Parent-child interactions and parenting have been identified as crucial points of intervention to support children's health and emotional well-being, yet few parenting interventions have been developed or evaluated for parents of young children. This paper describes a randomised controlled trial of a brief, group based parenting intervention for parents of young children (2-10 years) with type 1 diabetes compared against care as usual (CAU). METHODS/DESIGN: Families will be randomised to either Positive Parenting for Healthy Living Triple P or CAU. Positive Parenting for Healthy Living Triple P involves 2 * 2 h group sessions. Outcomes will be assessed via parent and child questionnaire, home observations and blood glucose monitoring at baseline, 1-month and 6-months post-intervention. Primary outcomes will be parent- and child-reported parenting behaviour, parent reported child behaviour and adjustment, and parent-reported child quality-of life. Secondary outcomes will include parental self-efficacy with diabetes management, illness-specific and general parenting stress, parent-reported child illness behaviour, family quality-of-life, observed parenting and child behaviour, and child's illness control. DISCUSSION: The theoretical background, study hypotheses, methods and planned analyses are discussed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613001281785 . Registered 20 November, 2013. PMID- 27659519 TI - Profiles of miRNAs matched to biology in aromatase inhibitor resistant breast cancer. AB - Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes. Affymetrix GeneChip miRNA2.0 arrays identified 184 miRNAs differentially expressed in 2A and 5C compared to E2-free wild-type MCF-7:WS8. In 5C, 34 miRNAs of the DLK1-DIO3 locus and miR-31 were overexpressed, whereas miR-222 was low. TCGA data revealed poor and favorable overall survival for low miR-31 and miR-222 levels, respectively (HR=3.0, 95% CI:1.9-4.8; HR=0.3, 95% CI:0.1-0.6). Targets of deregulated miRNAs were identified using CLIP-confirmed TargetScan predictions. KEGG enrichment analyses for 5C- and 2A-specific target gene sets revealed pathways associated with cell proliferation including insulin, mTOR, and ErbB signaling as well as immune response and metabolism. Key genes overrepresented in 5C- and 2A-specific pathway interaction networks including EGFR, IGF1R and PIK3R1 had lower protein levels in 5C compared to 2A and were found to be differentially modulated by respective miRNA sets. Distinct up-regulated miRNAs from the DLK1 DIO3 locus may cause these attenuative effects as they are predicted to interact with corresponding 3' untranslated regions. These new miRNA profiles become an important regulatory database to explore E2-induced apoptotic mechanisms of clinical relevance for the treatment of resistant breast cancer. PMID- 27659520 TI - Sirtuins in glucose and lipid metabolism. AB - Sirtuins are evolutionarily conserved protein, serving as nicotinamide adenine dinucleotide-dependent deacetylases or adenosine diphosphate-ribosyltransferases. The mammalian sirtuins family, including SIRT1~7, is involved in many biological processes such as cell survival, proliferation, senescence, stress response, genome stability and metabolism. Evidence accumulated over the past two decades has indicated that sirtuins not only serve as important energy status sensors but also protect cells against metabolic stresses. In this review, we summarize the background of glucose and lipid metabolism concerning sirtuins and discuss the functions of sirtuins in glucose and lipid metabolism. We also seek to highlight the biological roles of certain sirtuins members in cancer metabolism. PMID- 27659522 TI - Multi-cycle chemotherapy with the glycolipid-like polymeric micelles evade cancer stem cell enrichment in breast cancer therapy. AB - Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro, on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo, the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What's more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research. PMID- 27659521 TI - BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis. AB - BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling. Data from 297, 402 patients with BC were pooled from 34 studies. The median prevalence rates of BRCA1 and BRCA2 mutations were 14.5% and 8.3%, respectively. BRCA mutations were associated with worse OS (BRCA1: HR = 1.69, 95% CI, 1.35 to 2.12, p < 0.001; BRCA2: HR = 1.50, 95% CI 1.03 to 2.19, p = 0.034). However, this did not translate into poor BCSS (BRCA1: HR = 1.14, 95% CI, 0.81 to 1.16, p = 0.448; BRCA2: HR = 1.16; 95% CI 0.82 to 1.66, p = 0.401) or EFS (BRCA1: HR = 1.10, 95% CI, 0.86 to 1.41, p = 0.438; BRCA2: HR= 1.09; 95% CI 0.81 to 1.47, p = 0.558). Several studies analyzed BRCA1 and BRCA2 mutations together and found no impact on OS (HR = 1.21; 95% CI, 0.73 to 2.00, p = 0.454) or EFS (HR = 0.94; 95% CI, 0.60 to 1.48, p = 0.787). BRCA1 and BRCA2 mutations were associated with poor OS in patients with BC, but had no significant impact on BCSS or EFS. An improved survival was observed in BC patients who had BRCA1 mutation and treated with endocrinotherapy. The results may have therapeutic and prognostic implications important for BRCA mutation carriers with BC. PMID- 27659523 TI - Interferon-stimulated gene 15 induces cancer cell death by suppressing the NF kappaB signaling pathway. AB - Interferon-stimulated gene 15 (ISG15) is an important cytokine that has been reported in carcinogenesis. However, we found that ISG15 and de-ISGylase USP18 were induced by several anti-cancer agents, which was confirmed by both RT-PCR and immunoblotting assays. Further studies demonstrated that ectopic ISG15 and USP18 inhibited proliferation of myeloma, leukemia and cervical cancer cells. More importantly, ISG15 and USP18 induced cancer cell apoptosis. This finding was confirmed in a cervical xenograft model in which cervical cancer growth was suppressed by lentiviral ISG15. In the mechanistic study, ISG15 was found to disrupt the NF-kappaB signaling pathway by downregulating the expression of IKKbeta and p65, phosphorylation of p65 and IkappaBalpha. Consistent with this finding, ISG15 suppressed the expression of NF-kappaB recognition element-driving luciferase and decreased the transcription of XIAP and Mcl-1, two typical genes regulated by NF-kappaB. Therefore, the present study demonstrated that ISG15 induces cancer cell apoptosis by disrupting the NF-kappaB signaling pathway. This study highlighted a novel role of ISG15 in tumor suppression. PMID- 27659524 TI - Nodal signaling promotes vasculogenic mimicry formation in breast cancer via the Smad2/3 pathway. AB - Vasculogenic mimicry (VM) is a nonangiogenesis-dependent pathway that promotes tumor growth and disease progression. Nodal signaling has several vital roles in both embryo development and cancer progression. However, the effects of Nodal signaling on VM formation in breast cancer and its underlying mechanisms are ill defined. We analyzed the relationship between Nodal signaling and VM formation in one hundred human breast cancer cases and the results showed that the expression of Nodal was significantly correlated with VM formation, tumor metastasis, differentiation grade, TNM stage and poor prognosis. Furthermore, up-regulation of Nodal expression promoted VM formation of breast cancer cells in vitro and in vivo. Knockdown of Nodal expression restrained VM formation. In addition, Nodal induced EMT and up-regulated the expression of Slug, Snail and c-Myc. We found that blocking the Smad2/3 pathway by administering SB431542 inhibited VM formation in breast cancer cell lines and xenografts. Taken together, Nodal signaling through the Smad2/3 pathway up-regulated Slug, Snail and c-Myc to induce EMT, thereby promoting VM formation. Our study suggests that the Nodal signaling pathway may serve as a therapeutic target to inhibit VM formation and improve prognosis in breast cancer patients. PMID- 27659525 TI - A dose increased once-weekly bortezomib-based combination therapy for multiple myeloma. AB - BACKGROUND: The purpose of the current study was to evaluate the efficacy and safety of a dose increased weekly Bortezomib (Bor) based combination therapy in multiple myeloma (MM) patients. RESULTS: The overall response rate (ORR) in the modified Bor group was 76.6%, composed of 40% complete response (CR), 3.3% very good partial response (VGPR) and 33.3% partial response (PR). The ORR was 82.3%, with 26.5% CR, 5.9% VGPR and 50% PR in control. A subgroup analysis showed both groups had equal efficacy in newly diagnosed MM patients ( P = 1.000). The median progression free survival was 16 (11.7-20.3) months for the modified Bor group and 12 (10.5-13.5) months for the control (P = 0.503), and the median overall survival was 36 (9.4-62.6) vs 28 (21.6-34.4) months (P = 0.759). The incidences of AEs were similar except grade 1-4 peripheral neuropathy (PN) rate was 10% in modified regime group and 32.4% in control (P = 0.038). MATERIALS AND METHODS: This was a monocentric, prospective, non-randomized, phase IV, non-inferiority trial. Thirty MM patients were treated with modified Bor-based combination therapy (Bor 1.6 mg/m2 on day 1, 8), with 34 MM patients on conventional Bor based combination therapy (1.3 mg/m2 on day 1, 4, 8, 11) as control. The responses and adverse events (AEs) were compared. CONCLUSIONS: The increased-dose weekly Bor-based combination therapies were not inferior to conventional ones in terms of response and survival benefit, but showed lower rate of peripheral neuropathy (PN). PMID- 27659526 TI - Acetylation of androgen receptor by ARD1 promotes dissociation from HSP90 complex and prostate tumorigenesis. AB - Prostate cancer is an androgen receptor (AR)-driven disease and post translational modification of AR is critical for AR activation. We previously reported that Arrest-defective protein 1 (ARD1) is an oncoprotein in prostate cancer. It acetylates and activates AR to promote prostate tumorigenesis. However, the ARD1-targeted residue within AR and the mechanisms of the acetylation event in prostate tumorigenesis remained unknown. In this study, we show that ARD1 acetylates AR at lysine 618 (K618) in vitro and in vivo. An AR construct with the charged lysine substitution by arginine (AR-618R) reduces RNA Pol II binding, AR transcriptional activity, prostate cancer cell growth, and xenograft tumor formation due to attenuation of AR nuclear translocation, whereas, construct mimicking neutral polar substitution acetylation at K618 by glutamine (AR-618Q) enhanced these effects beyond that of the wild-type AR. Mechanistically, ARD1 forms a ternary complex with AR and HSP90 in vitro and in vivo. Expression of ARD1 increases levels of AR acetylation and AR-HSP90 dissociation in a dose dependent manner. Moreover, the AR acetylation defective K618R mutant is unable to dissociate from HSP90 while the HSP90-dissociated AR is acetylated following ligand exposure. This work identifies a new mechanism for ligand-induced AR-HSP90 dissociation and AR activation. Targeting ARD1-mediated AR acetylation may be a potent intervention for AR-dependent prostate cancer therapy. PMID- 27659527 TI - MMP-1 promoter polymorphism is associated with risk of radiation-induced lung injury in lung cancer patients treated with radiotherapy. AB - Matrix metalloproteinase-1 (MMP-1) has been implicated in several inflammatory and fibrotic diseases. We hypothesized that genetic variations in the MMP1 promoter region are associated with risk of radiation-induced lung injury (RILI). A cohort of 251 lung cancer patients was genotyped for five single nucleotide polymorphisms in the MMP1 promoter region. We found that rs1144393 AG/GG was strongly correlated with an increased occurrence of grade >= 2 RILI (p = 0.002). Additionally, patients with the rs1144393 AG/GG genotypes exhibited higher MMP-1 expression than patients with the AA genotype in lung tissues (n = 28, p = 0.022) and plasma samples (n = 40, p = 0.018). Our results indicated that rs1144393 in the MMP1 promoter region can be a predictor of grade >= 2 RILI in lung cancer patients treated with thoracic radiation. PMID- 27659528 TI - Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway. AB - Paclitaxel, a taxane, is a cytotoxic chemotherapeutic agent that targets microtubules. It has become a front-line therapy for a broad range of malignancies, including lung, breast, gastric, esophageal, and bladder carcinomas. Although paclitaxel can inhibit tumor development and improve survival, poor solubility, myelotoxicity, allergic reactions, and drug resistance have restricted its clinical application. Paclitaxel is frequently combined with other chemotherapeutics to enhance the antitumor effects and reduce side effects. We synthesized geridonin, a derivative of oridonin, and demonstrate that geridonin and paclitaxel act synergistically to inhibit the growth of gastric cancer cells. Importantly, geridonin enhanced the antitumor effects of paclitaxel without increasing toxicity in vivo. Mechanistic analysis revealed that administration of geridonin in combination with paclitaxel up-regulated the tumor suppressor PTEN and inhibited phosphorylation of Akt and MDM2. This led to the accumulation of p53 and induced apoptosis though the mitochondrial pathway. Thus, geridonin in combination with paclitaxel is a new treatment strategy for gastric cancer. PMID- 27659529 TI - Induction of anti-EGFR immune response with mimotopes identified from a phage display peptide library by panitumumab. AB - The epidermal growth factor receptor (EGFR) is overexpressed in several epithelial tumors. Anti-EGFR humanized monoclonal antibodies, cetuximab and panitumumab, in combination with chemotherapy have improved the prognosis for patients with wild-type RAS tumors. To identify mimotopes of EGFR and develop mimotope-based EGFR vaccines, we screened a phage display peptide library with panitumumab. Two EGFR mimotopes P19 and P26, which could be recognized by panitumumab specifically, were isolated. To enhance the immune responses, we generated recombinant proteins of P19 or P26 fused to a heat-shock cognate protein 70 (Hsc70), and evaluated the efficacy of Hsc70-P19 and Hsc70-P26 as vaccines in vivo. Immunization with Hsc70-P19 or Hsc70-P26 fusion protein stimulated the immune system to produce specific antibodies against peptides as well as EGFR. Moreover, antibodies elicited against mimotopes could induce antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and inhibit the proliferation of EGFR-overexpressing A431 cells. Treatment with Hsc70-P19 and Hsc70-P26 significantly reduced tumor growth in BALB/c transplantable lung cancer models. Although there was no sequence homology between the phage-derived peptides and EGFR by alignments, both peptides mimic the conformational structure of EGFR binding to panitumumab. In conclusion, the mimotopes we identified from phage display peptide library could be promising candidate vaccines for active anti-EGFR immunotherapy against cancers. PMID- 27659530 TI - CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype. AB - The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5 FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell like cells. PMID- 27659531 TI - The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells. AB - We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM. PMID- 27659532 TI - Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors. AB - HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation and metastasis by interacting with the PRC2 complex and the modulation of its target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and promotion of GISTs. The expression of HOTAIR was found to be higher in surgically resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was associated with cell cycle progression, and controlled the invasion and migration of GIST cells. Using a gene expression microarray and lists of HOTAIR-associated candidate genes, we suggested that protocadherin 10 (PCDH10) is a key molecule. PCDH10 expression was significantly decreased in GIST-T1 and GIST882 cells, possibly as a consequence of hypermethylation. We observed that HOTAIR induced PCDH10 methylation in a SUZ12-dependent manner. In this study, we found that the malignant character of GISTs was initiated and amplified by PCDH10 in a process regulated by HOTAIR. In summary, our findings imply that PCDH10 and HOTAIR may be useful markers of disease progression and therapeutic targets. PMID- 27659533 TI - Circulating vascular endothelial growth factor (VEGF) as predictive factor of progression-free survival in patients with advanced chordoma receiving sorafenib: an analysis from a phase II trial of the french sarcoma group (GSF/GETO). AB - BACKGROUND: Patients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874). RESULTS: From May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p<0.001) was noted along with a non-significant increase in VEGF (0.7 vs 1.0 ng/mL, p=0.07). VEGF at D1 >1.04 ng/mL (HR=12.5, 95% CI: 1.37-114, p=0.025) and VEGF at D7 >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p=0.037) were associated with shorter PFS. The 9-month PFS rate was 92.3% (95% CI: 56.6-98.9) when VEGF at D1 was <=1.04 ng/mL versus 23.3% (95%-CI: 1.0-63.2) when >1.04 ng/mL. PATIENTS AND METHODS: Chordoma patients were treated with sorafenib 800 mg/day for 9 months, unless earlier occurrence of progression or toxicities. Six biomarkers (sE-Selectin, VEGF, VEGF-C, placental growth factor (PlGF), Thrombospondin, Stem Cell Factor (SCF)) were measured at baseline (day 1: D1) and day 7 (D7). CONCLUSION: High levels of VEGF was associated with poor outcome. PMID- 27659534 TI - Tumor-specific gene therapy for pancreatic cancer using human neural stem cells encoding carboxylesterase. AB - Advanced pancreatic cancer is one of the most lethal malignant human diseases lacking effective treatment. Its extremely low survival rate necessitates development of novel therapeutic approach. Human neural stem cells (NSCs) are known to have tumor-tropic effect. We genetically engineered them to express rabbit carboxyl esterase (F3.CE), which activates prodrug CPT-11(irinotecan) into potent metabolite SN-38. We found significant inhibition of the growth of BxPC3 human pancreatic cancer cell line in vitro by F3.CE in presence of CPT-11. Apoptosis was also markedly increased in BxPC3 cells treated with F3.CE and CPT 11. The ligand VEGF and receptor VEGF-1(Flt1) were identified to be the relevant tumor-tropic chemoattractant. We confirmed in vivo that in mice injected with BxPC3 on their skin, there was significant reduction of tumor size in those treated with both F3.CE and BxPC3 adjacent to the cancer mass. Administration of F3.CE in conjunction with CPT-11 could be a new possibility as an effective treatment regimen for patients suffering from advanced pancreatic cancer. PMID- 27659535 TI - Generation of affibody molecules specific for HPV16 E7 recognition. AB - Cervical cancer caused by infection with high-risk human papillomavirus remains to be the most deadly gynecologic malignancy worldwide. It is well documented that persistent expression of two oncogenes (E6/E7) plays the key roles in cervical cancer. Thus, in vivo detection of the oncoproteins is very important for the diagnosis of the cancer. Recently, affibody molecules have been demonstrated to be a powerful targeting probe for tumor-targeted imaging and diagnosis. In this study, four HPV16 E7-binding affibody molecules (Z HPV16 E7127, Z HPV16E7301, Z HPV16E7384 and Z HPV16E7745) were screened from a phage displayed peptide library and used for molecular imaging in tumor-bearing mice. Biosensor binding analyses showed first that the four affibody molecules bound to HPV16 E7 with very high affinity and specificity. They co-localized with E7 protein only in two HPV16-positive cancer cells (SiHa and CaSki). Furthermore, affibody ZHPV16E7384 was conjugated with Dylight755 and used for in vivo tumor imaging. Strongly high-contrast tumor retention of this affibody only occurred in HPV16-derived tumors of mice as early as 30 min post-injection, not in HPV negative and HPV18-derived tumors. The accumulation of Dylight755-conjugated ZHPV16E7384 in tumor was achieved over a longer time period (24 h). The data here provide strong evidence that E7-specific affibody molecules have great potential used for molecular imaging and diagnosis of HPV-induced cancers. PMID- 27659537 TI - Cystic brain metastasis is associated with poor prognosis in patients with advanced breast cancer. AB - PURPOSE: Brain metastasis (BM) with a cystic component from breast cancer is rare and largely uncharacterized. The purpose of this study was to identify the characteristics of cystic BM in a large cohort of breast cancer patients. RESULTS: A total of 35 eligible patients with cystic BM and 255 patients with solid BM were analyzed. Three factors were significantly associated with an increased probability of developing cystic lesions: age at diagnosis <= 40 years, age at BM <= 45 years, and poor histological grade (p < 0.05). Patients with cystic metastasis were also characterized by a larger metastasis volume, a shorter progression-free survival (PFS) following their first treatment for BM, and poor overall survival after BM (p < 0.05). Multivariate analysis further demonstrated that local control of cystic BM was only potentially achieved for HER2-negative primary tumors (p = 0.084). METHODS: Breast cancer patients with parenchymal BM were reviewed from consecutive cases treated at our institution. Cystic BM was defined when the volume of a cystic lesion was greater than 50% of the aggregated volume of all lesions present. Clinicopathologic and radiographic variables were correlated with development of cystic lesions and with prognosis of cystic BM. CONCLUSIONS: This study shows that cystic BM from breast cancer, a special morphological type of BM, had worse prognosis than the more commonly observed solid BM. Younger age and low tumor grade were associated with the development of cystic lesions. Further comprehensive research and management of cystic BM are warranted to improve its poor prognosis. PMID- 27659536 TI - MDM2 is a potential therapeutic target and prognostic factor for ovarian clear cell carcinomas with wild type TP53. AB - MDM2, a ubiquitin ligase, suppresses wild type TP53 via proteasome-mediated degradation. We evaluated the prognostic and therapeutic value of MDM2 in ovarian clear cell carcinoma. MDM2 expression in ovarian cancer tissues was analyzed by microarray and real-time PCR, and its relationship with prognosis was evaluated by Kaplan-Meier method and log-rank test. The anti-tumor activities of MDM2 siRNA and the MDM2 inhibitor RG7112 were assessed by cell viability assay, western blotting, and flow cytometry. The anti-tumor effects of RG7112 in vivo were examined in a mouse xenograft model. MDM2 expression was significantly higher in clear cell carcinoma than in ovarian high-grade serous carcinoma (P = 0.0092) and normal tissues (P = 0.035). High MDM2 expression determined by microarray was significantly associated with poor progression-free survival and poor overall survival (P = 0.0002, and P = 0.0008, respectively). Notably, RG7112 significantly suppressed cell viability in clear cell carcinoma cell lines with wild type TP53. RG7112 also strongly induced apoptosis, increased TP53 phosphorylation, and stimulated expression of the proapoptotic protein PUMA. Similarly, siRNA knockdown of MDM2 induced apoptosis. Finally, RG7112 significantly reduced the tumor volume of xenografted RMG-I clear cell carcinoma cells (P = 0.033), and the density of microvessels (P = 0.011). Our results highlight the prognostic value of MDM2 expression in clear cell carcinoma. Thus, MDM2 inhibitors such as RG7112 may constitute a class of potential therapeutics. PMID- 27659540 TI - Craniometric examination of Longxian and Qi Li Cun archaeological sites to assess population continuity in ancient northern China. AB - In this paper, population continuity and discontinuity in northern China are explored using craniometric analyses from two archaeological sites, Longxian (Warring States) and Qi Li Cun (Han Dynasty). Neither population has been previously studied. Artefactual evidence shows the individuals from Qi Li Cun were Xianbei, descendants from Mongolia. Longxian is from further south in the central plains at an earlier time, thus, we expect to observe variability between these groups. In total, 24 cranial measurements were obtained on 66 crania from these sites. Howells's cranial measurements on Anyang (42 crania) and Hainan (83 crania) Chinese samples were included for comparative purposes. Less variability is expected between Longxian and Howells's Chinese data due to geographic and temporal similarity. With closer geographic and temporal affinity with Anyang, the expectation is for Longxian and Anyang to be similar. Few statistical differences exist between Longxian and Qi Li Cun; this was supported by the similarity found through principal components analysis (PCA). Regardless of sex, canonical discriminant analysis shows clustering of Longxian and Qi Li Cun separate from those of Anyang and Hainan. Their similarity indicates the people from Longxian and Qi Li Cun likely share Mongolian ancestry. Our results, supported by other studies, suggest that despite temporal differences, Mongolians living in China during the Warring States and Han dynasty retained their cultural and genetic Mongolian identity. These data add valuable bioarchaeological information regarding the peopling of northern China during a crucial period of cultural and political change in the Early Bronze Age and Iron Age. PMID- 27659538 TI - The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization. AB - Macrophages occur as resident cells of fetal origin or as infiltrating blood monocyte-derived cells. Despite the critical role of tumor-associated macrophages (TAMs) in tumor progression, the contribution of these developmentally and functionally distinct macrophage subsets and their alteration by the tumor microenvironment are poorly understood. We have addressed this question by comparing TAMs from human ovarian carcinoma ascites, resident peritoneal macrophages (pMPHs) and monocyte-derived macrophages (MDMs). Our study revealed striking a similarity between TAMs and pMPHs, which was considerably greater that the resemblance of TAMs and MDMs, including their transcriptomes, their inflammation-related activation state, the presence of receptors mediating immune functions and the expression of tumor-promoting mediators. Consistent with these results, TAMs phagocytized bacteria, presented peptide antigens and activated cytotoxic T cells within their pathophysiological environment. These observations support the notion that tumor-promoting properties of TAMs may reflect, at least to some extent, normal features of resident macrophages rather than functions induced by the tumor microenvironment. In spite of these surprising similarities between TAMs and pMPHs, bioinformatic analyses identified a TAM-selective signature of 30 genes that are upregulated relative to both pMPHs and MDMs. The majority of these genes is linked to extracellular matrix (ECM) remodeling, supporting a role for TAMs in cancer cell invasion and ovarian cancer progression. PMID- 27659541 TI - Sexual dimorphism in two mediaeval Muslim populations from Spain. AB - Sexual dimorphism in humans is mainly observed as a difference in the anatomy of genitals and breasts. There are also some differences in the stature and metric or morphological traits of the skeleton. Degree of sexual dimorphism varies among populations and depends on their genetic composition and various cultural and environmental factors. In this study, two Mediaeval Muslim populations from Granada, Spain, were compared, testing whether differences in living environment (urban vs. rural) would result in distinct degrees of sexual dimorphism of long bones. We studied skeletal material from urban (Sahl ben Malik, Granada, Spain) and rural (La Torrecilla, Arenas del Rey, Granada, Spain) cemeteries. Only adult individuals (66 from Sahl ben Malik and 72 from La Torrecilla) were selected for the study. Maximum length, minimum circumference of the shaft and maximum widths of the proximal and distal epiphyses were measured in each bone. The index of sexual dimorphism (ISD) was calculated for each variable and each population. The degree of sexual dimorphism was greater in La Torrecilla. These results indicate that Muslim women in large urban centres may have played a more active role in social and working life in comparison to their rural counterparts and may have enjoyed superior living conditions, which contributed to enhancing the body development of women and reducing sexual dimorphism. We conclude that living in an urban or a rural environment may influence the degree of sexual dimorphism. PMID- 27659539 TI - A virtual water maze revisited: Two-year changes in navigation performance and their neural correlates in healthy adults. AB - Age-related declines in spatial navigation are associated with deficits in procedural and episodic memory and deterioration of their neural substrates. For the lack of longitudinal evidence, the pace and magnitude of these declines and their neural mediators remain unclear. Here we examined virtual navigation in healthy adults (N=213, age 18-77 years) tested twice, two years apart, with complementary indices of navigation performance (path length and complexity) measured over six learning trials at each occasion. Slopes of skill acquisition curves and longitudinal change therein were estimated in structural equation modeling, together with change in regional brain volumes and iron content (R2* relaxometry). Although performance on the first trial did not differ between occasions separated by two years, the slope of path length improvement over trials was shallower and end-of-session performance worse at follow-up. Advanced age, higher pulse pressure, smaller cerebellar and caudate volumes, and greater caudate iron content were associated with longer search paths, i.e. poorer navigation performance. In contrast, path complexity diminished faster over trials at follow-up, albeit less so in older adults. Improvement in path complexity after two years was predicted by lower baseline hippocampal iron content and larger parahippocampal volume. Thus, navigation path length behaves as an index of perceptual-motor skill that is vulnerable to age-related decline, whereas path complexity may reflect cognitive mapping in episodic memory that improves with repeated testing, although not enough to overcome age-related deficits. PMID- 27659542 TI - Assessing size and strength of the clavicle for its usefulness for sex estimation in a British medieval sample. AB - The construction of the biological profile from human skeletal remains is the foundation of anthropological examination. However, remains may be fragmentary and the elements usually employed, such as the pelvis and skull, are not available. The clavicle has been successfully used for sex estimation in samples from Iran and Greece. In the present study, the aim was to test the suitability of the measurements used in those previous studies on a British Medieval population. In addition, the project tested whether discrimination between sexes was due to size or clavicular strength. The sample consisted of 23 females and 25 males of pre-determined sex from two medieval collections: Poulton and Gloucester. Six measurements were taken using an osteometric board, sliding calipers and graduated tape. In addition, putty rings and bi-planar radiographs were made and robusticity measures calculated. The resulting variables were used in stepwise discriminant analyses. The linear measurements allowed correct sex classification in 89.6% of all individuals. This demonstrates the applicability of the clavicle for sex estimation in British populations. The most powerful discriminant factor was maximum clavicular length and the best combination of factors was maximum clavicular length and circumference. This result is similar to that obtained by other studies. To further investigate the extent of sexual dimorphism of the clavicle, the biomechanical properties of the polar second moment of area J and the ratio of maximum to minimum bending rigidity are included in the analysis. These were found to have little influence when entered into the discriminant function analysis. PMID- 27659543 TI - Non-invasive detection of 2-hydroxyglutarate in IDH-mutated gliomas using two dimensional localized correlation spectroscopy (2D L-COSY) at 7 Tesla. AB - BACKGROUND: Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the "oncometabolite" 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly sensitive non-invasive technique for assessing brain metabolism. This study aims to assess tumor metabolism using 2D L-COSY at 7T for the detection of 2HG in IDH mutant gliomas. METHODS: Nine treatment-naive patients with suspected intracranial neoplasms were scanned at 7T MRI/MRS scanner using the 2D L-COSY technique. 2D-spectral processing and analyses were performed using a MATLAB based reconstruction algorithm. Cross and diagonal peak volumes were quantified in the 2D L-COSY spectra and normalized with respect to the creatine peak at 3.0 ppm and quantified data were compared with previously-published data from six normal subjects. Detection of 2HG was validated using findings from immunohistochemical (IHC) staining in patients who subsequently underwent surgical resection. RESULTS: 2HG was detected in both of the IDH-mutated gliomas (grade III Anaplastic Astrocytoma and grade II Diffuse Astrocytoma) and was absent in IDH wild-type gliomas and in a patient with breast cancer metastases. 2D L-COSY was also able to resolve complex and overlapping resonances including phosphocholine (PC) from glycerophosphocholine (GPC), lactate (Lac) from lipids and glutamate (Glu) from glutamine (Gln). CONCLUSIONS: This study demonstrates the ability of 2D L-COSY to unambiguously detect 2HG in addition to other neuro metabolites. These findings may aid in establishing 2HG as a biomarker of malignant progression as well as for disease monitoring in IDH-mutated gliomas. PMID- 27659544 TI - A Randomized Multicenter Clinical Trial of Ultrathin Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) versus DSAEK. AB - OBJECTIVE: To compare visual acuity, refraction, endothelial cell density (ECD), and complications after Descemet stripping automated endothelial keratoplasty (DSAEK) and ultrathin DSAEK (UT-DSAEK). DESIGN: A multicenter, prospective, double-masked, randomized, controlled clinical trial. PARTICIPANTS: From 66 patients with irreversible corneal endothelial dysfunction dues to Fuchs' dystrophy who enrolled from 4 tertiary medical centers in the Netherlands, 66 eyes were studied. METHODS: Participants were centrally randomized to undergo either UT-DSAEK or DSAEK, based on preoperative best spectacle-corrected visual acuity (BSCVA), recipient central corneal thickness, patient age, and recruitment center. Donor corneas were precut by a single cornea bank. PARTICIPANTS: Participants underwent ophthalmic examinations preoperatively and 3, 6, and 12 months after the operation, including manifest refraction, BSCVA using an Early Treatment Diabetic Retinopathy Study chart, and endothelium imaging. MAIN OUTCOME MEASURES: BSCVA 12 months postoperatively. RESULTS: Preoperative BSCVA did not differ between patients undergoing DSAEK (0.35 logarithm of the minimum angle of resolution [logMAR] [95% confidence interval {CI} 0.27-0.43]; n = 32) and UT DSAEK (0.37 logMAR [95% CI 0.31-0.43]; n = 34; P = 0.8). BSCVA was significantly better after UT-DSAEK compared with that after DSAEK at 3 months (0.17 logMAR [95% CI 0.13-0.21], n = 31 vs. 0.28 logMAR [95% CI 0.23-0.33], n = 31; P = 0.001), 6 months (0.14 logMAR [95% CI 0.10-0.18], n = 30 vs. 0.24 logMAR [95% CI 0.20-0.28], n = 30; P = 0.002), and 12 months (0.13 logMAR [95% CI 0.09-0.17], n = 33 vs. 0.20 logMAR [95% CI 0.15-0.25], n = 29; P = 0.03). Refraction, ECD loss (40% at 3 months; P < 0.001), donor loss (DSAEK n = 2 vs. UT-DSAEK n = 3 [relative risk {RR} 1.4 {95% CI 0.24-7.5}; P = 0.7]), and graft dislocation (DSAEK n = 5 vs. UT-DSAEK n = 5 [RR 1.0 {95% CI 0.34-3.33}; P = 0.9]) did not differ between UT-DSAEK and DSAEK. Donor thickness was significantly thinner for UT-DSAEK (101 MUm [95% CI 93-110 MUm]; range 50-145 MUm) than for DSAEK (209 MUm [95% CI 196-222 MUm]; range 147-289 MUm; P < 0.001). CONCLUSIONS: This study indicates that compared with DSAEK, UT-DSAEK results in faster and better recovery of BSCVA with similar refractive outcomes, endothelial cell loss, and incidence of complications. PMID- 27659545 TI - Demographic, Systemic, and Ocular Factors Associated with Nonarteritic Anterior Ischemic Optic Neuropathy. AB - OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for >=2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had >=1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1%) developed NAION during a mean +/- standard deviation (SD) follow-up of 7.8+/-3.1 years. The mean +/- SD age for NAION cases at the index date was 64.0+/-9.2 years vs. 58.4+/-9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2% increased hazard of NAION (HR = 1.02; 95% CI: 1.01-1.03). Female subjects had a 36% decreased hazard of developing NAION (HR = 0.64; 95% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46% decreased hazard of developing NAION (HR = 0.54; 95% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR = 0.91; 95% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR = 1.62; 95% CI: 1.26-2.07) and hypercoagulable states (HR = 2.46; 95% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P = 0.45), patients with end-organ involvement from DM had a 27% increased hazard of NAION relative to those with uncomplicated DM (HR = 1.27; 95% CI: 1.01 1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR = 1.29; 95% CI: 1.08-1.54) and retinal vein occlusion (HR = 3.94; 95% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition. PMID- 27659546 TI - Pediatric Hypertension: Are Pediatricians Following Guidelines? AB - The National Heart, Lung, and Blood Institute recommends that children older than 3 years seen in the medical setting have their blood pressure (BP) measured. The authors aimed to determine whether BPs are measured at well-child visits and whether elevated readings are recognized. A retrospective chart review of 3- to 18-year-old children seen for well-child visits was performed. Age, sex, weight, height, BP, extremity measured, and type of intervention were collected. BP was measured in 777 of 805 patients (97%). BP was elevated in 158 patients (20%). A total of 95 patients (60%) did not receive any intervention. Not recognizing elevated BP was associated with increased daily patient load (17.9+/-6.5 vs 12.6+/-5.5, P=.001). Higher body mass index was associated with elevated BP (P=.0008) but was not associated with improved recognition. Findings show that BP is almost always measured at well-child visits but is not being measured appropriately, and general pediatric clinics are not consistently following BP management recommendations. PMID- 27659547 TI - The link between self-perceptions of aging, cancer view and physical and mental health of older people with cancer: A cross-sectional study. AB - OBJECTIVES: Older people may suffer from stigmas linked to cancer and aging. Although some studies suggested that a negative view of cancer may increase the level of depression, such an association has never been studied in the elderly population. Similarly, even though it is established that a negative self perception of aging has deleterious consequences on mental and physical health in normal aging, the influence in pathological contexts, such as oncology, has not been studied. The main aim of this study is thus to analyze the effect of these two stigmas on the health of elderly oncology patients. MATERIALS AND METHODS: 101 patients suffering from a cancer (breast, gynecological, lung or hematological) were seen as soon as possible after their diagnosis. Their self perception of age, cancer view and health (physical and mental) was assessed. RESULTS: Multiple regressions showed that patients with a more negative self perception of aging and/or more negative cancer view reported poorer global health. We also observed that negative self-perception of aging was associated with worse physical and mental health, whereas negative cancer views were only linked to worse mental health. No interaction was observed between these two stigmas, suggesting that their action is independent. CONCLUSION: Older patients with cancer face double stigmatization, due to negative self-perception of aging and cancer, and these stigmas have impacts on global and mental health. Self perception of aging is also linked to physical health. Longitudinal studies will be necessary to analyze the direction of the association between this double stigmatization and health. PMID- 27659548 TI - The impact of age on first-line systemic therapy in patients with metachronous metastases from colorectal cancer. AB - OBJECTIVES: The paucity of evidence for the optimal use of systemic therapy in elderly patients with metastatic colorectal cancer (mCRC) poses significant challenges to cancer specialists. The present population-based study provides insight into the impact of age on palliative systemic therapy in patients with metachronous metastases from CRC, in order to optimize the decision-making process. METHODS: Data on the development and treatment of metachronous metastases were collected for patients with primary resected CRC diagnosed between 2003 and 2008 in the Eindhoven area of the Netherlands Cancer Registry. Patients undergoing surgery for metastases were excluded, resulting in a study population treated with palliative intent, with or without systemic therapy (n=746). RESULTS: 385 patients received palliative systemic therapy (52%). Patients aged >=75years were less likely to receive systemic therapy (31% >=75years vs 73% <60years) and more likely to receive single-agent chemotherapy than combination-chemotherapy. Elderly patients (>=75years) treated with capecitabine-oxaliplatin (CAPOX) received fewer cycles (51% <=3 oxaliplatin cycles, 43% <=3 capecitabine cycles) and lower cumulative dosages compared to patients aged <75years, although initial dosages were similar. If capecitabine monotherapy (CapMono) was administered, starting dosages were 2414mg/m2/d<75years and 1992mg/m2/d>=75years (p<0.05), but no differences in number of received cycles or cumulative dosages were observed. CONCLUSION: Age beginning at 75years significantly influenced palliative systemic therapy. Even in selected elderly patients, first-line treatment with CAPOX was associated with less cycles and lower cumulative dosages compared to younger patients. With single-agent fluoropyrimidine therapy, however, no such results were observed. PMID- 27659549 TI - Major discrepancies between what clinical trial registries record and paediatric randomised controlled trials publish. AB - BACKGROUND: Whether information from clinical trial registries (CTRs) and published randomised controlled trial (RCTs) differs remains unknown. Knowing more about discrepancies should alert those who rely on RCTs for medical decision making to possible dissemination or reporting bias. To provide help in critically appraising research relevant for clinical practice we sought possible discrepancies between what CTRs record and paediatric RCTs actually publish. For this purpose, after identifying six reporting domains including funding, design, and outcomes, we collected data from 20 consecutive RCTs published in a widely read peer-reviewed paediatric journal and cross-checked reported features with those in the corresponding CTRs. METHODS: We collected data for 20 unselected, consecutive paediatric RCTs published in a widely read peer-reviewed journal from July to November 2013. To assess discrepancies, two reviewers identified and scored six reporting domains: funding and conflict of interests; sample size, inclusion and exclusion criteria or crossover; primary and secondary outcomes, early study completion, and main outcome reporting. After applying the Critical Appraisal Skills Programme (CASP) checklist, five reviewer pairs cross-checked CTRs and matching RCTs, then mapped and coded the reporting domains and scored combined discrepancy as low, medium and high. RESULTS: The 20 RCTs were registered in five different CTRs. Even though the 20 RCTs fulfilled the CASP general criteria for assessing internal validity, 19 clinical trials had medium or high combined discrepancy scores for what the 20 RCTs reported and the matched five CTRs stated. All 20 RCTs selectively reported or failed to report main outcomes, 9 had discrepancies in declaring sponsorship, 8 discrepancies in the sample size, 9 failed to respect inclusion or exclusion criteria, 11 downgraded or modified primary outcome or upgraded secondary outcomes, and 13 completed early without justification. The CTRs for seven trials failed to index automatically the URL address or the RCT reference, and for 12 recorded RCT details, but the authors failed to report the results. CONCLUSIONS: Major discrepancies between what CTRs record and paediatric RCTs publish raise concern about what clinical trials conclude. Our findings should make clinicians, who rely on RCT results for medical decision-making, aware of dissemination or reporting bias. Trialists need to bring CTR data and reported protocols into line with published data. PMID- 27659552 TI - Transcatheter arterial embolization as first-line rescue in intractable primary postpartum hemorrhage: Assessment, outcome, and subsequent fertility. AB - BACKGROUND/PURPOSE: To assess the risk factors for intractable and controllable postpartum hemorrhage (PPH) and to evaluate the safety, efficacy, and outcome of transcatheter arterial embolization (TAE). METHODS: An emergency PPH rescue system including the 24-hour-available TAE was established in 2004. TAE with gelatine sponge particles placed on bilateral uterine or internal iliac arteries served as the first-line treatment for intractable PPH. Delivery methods, parity, causes of bleeding, clinical vital signs, coagulopathy, success rate, resumption of menstruation, and subsequent pregnancy outcome after TAE were recorded. RESULTS: From the years 2005 to 2013, 301 women experienced PPH, of whom 178 had controllable PPH and 123 intractable PPH. Tachycardia and disseminated intravascular coagulation were significant risk factors for intractable PPH. All of the women with intractable PPH underwent TAE, and 89 (72.3%) were transferred by ground transport to receive treatment in this system. The mean travel distance was 15 km +/- 12.5 km. The mean time of order to angiography room was 24.9 minutes +/- 14.2 minutes. The mean blood loss before TAE was 2247 mL +/- 1482 mL (range, 900-11,110 mL). The first TAE successfully controlled bleeding in 118 of the 123 (95.9%) women with intractable PPH. Of the 70 women with complete follow up, 69 (98.6%) recovered menstruation. Twenty-three women tried to get pregnant and 19 (82.6%) of them succeeded, giving birth to 12 full-term live infants. CONCLUSION: TAE was safe and effective in treating intractable primary PPH with a high success rate and preservation of menstruation and fertility. PMID- 27659550 TI - RAB23, regulated by miR-92b, promotes the progression of esophageal squamous cell carcinoma. AB - RAB23, a member of Ras-related small GTPase family, has been reported to be up regulated in several cancer types. However, its biological functions and the underlying molecular mechanisms for its oncogenic roles in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we have shown that the expression of RAB23 was elevated in ESCC tissues and ESCC cells. Overexpression of RAB23 promoted the growth and migration of the ESCC cells, while knocking down the expression RAB23 inhibited the growth, migration and metastasis of the ESCC cells. The molecular mechanism study showed that RAB23 activated beta-catenin/TCF signaling and regulated the expression of several target genes. In the further study, it was found that the expression of RAB23 was regulated by the miR-92b. Forced expression of MiR-92b decreased the mRNA and protein level of RAB23, and RAB23 rescued the biological functions of miR-92b. Taken together, this study revealed the oncogenic roles and the regulation of RAB23 in ESCC, suggesting RAB23 might be a therapeutic target. PMID- 27659554 TI - Dopamine D1 signaling involvement in the effects of the phosphodiesterase 10A inhibitor, PDM-042 on cognitive function and extrapyramidal side effect in rats. AB - Inhibition of phosphodiesterase 10A (PDE10A) results in activation of a dopamine D1 receptor-mediated direct pathway in addition to a dopamine D2 receptor mediated indirect pathway in the striatum. Therefore, PDE10A inhibitors could be novel therapeutics for schizophrenia, which differ from the currently available antipsychotics that directly block the dopamine D2 receptor. Previously, we found that a novel PDE10A inhibitor, PDM-042, had antipsychotic-like activity similar to currently available antipsychotics and minimal cataleptic effects in rats. The purpose of the present study was to examine the pharmacological effects of PDM 042 on cognitive function and extrapyramidal side effect. In addition, we aimed to examine whether these effects were mediated by activation of dopamine D1 signaling in rats. PDM-042 (1-3mg/kg) resulted in better discrimination of a novel object from a familiar one 48h after the acquisition trial, suggesting that PDM-042 increased object recognition memory. A dopamine D1 receptor antagonist, SCH23390 (0.1mg/kg), significantly blocked the enhancement of the object recognition memory induced by PDM-042 (3mg/kg) without affecting the recognition index by itself. We also found that the cataleptic effect of PDM-042 (1mg/kg) was significantly enhanced by SCH23390 (0.01-0.03mg/kg). These results indicate that PDM-042 has the potential to increase object recognition memory and that the cognitive enhancing and cataleptic effects of PDM-042 are mediated at least by activation of dopamine D1 signaling. PMID- 27659553 TI - Using a cultural and RDoC framework to conceptualize anxiety in Asian Americans. AB - Asian Americans are one of the fastest growing minority groups in the United States; however, mental health within this population segment, particularly anxiety disorders, remains significantly understudied. Both the heterogeneity within the Asian American population and the multidimensional nature of anxiety contribute to difficulties in understanding anxiety in this population. The present paper reviewed two sources of heterogeneity within anxiety in Asian Americans: (1) cultural variables and (2) mechanisms or components of anxiety. Specifically, we examined four cultural variables most commonly found in research related to anxiety in Asian Americans: acculturation, loss of face, affect valuation, and individualism-collectivism. We also discussed ways to parse anxiety through a Research Domain Criteria (RDoC) framework, specifically focusing on sensitivity to acute and potential threat, constructs within the Negative Valence System. Previously unpublished preliminary data were presented to illustrate one way of examining ethnic differences in anxiety using an RDoC framework. Finally, this paper offered recommendations for future work in this area. PMID- 27659555 TI - Detrimental effect of clomipramine on hippocampus-dependent learning in an animal model of obsessive-compulsive disorder induced by sensitization with d2/d3 agonist quinpirole. AB - Quinpirole (QNP) sensitization is one of the commonly used animal models of obsessive-compulsive disorder (OCD). We have previously shown that QNP-sensitized animals display a robust cognitive flexibility deficit in an active place avoidance task with reversal in Carousel maze. This is in line with numerous human studies showing deficits in cognitive flexibility in OCD patients. Here we explored the effect of clomipramine, an effective OCD drug that attenuates compulsive checking in QNP, on sensitized rats in acquisition and reversal performances in an active place avoidance task. We found that the addition of clomipramine to QNP-sensitization impairs acquisition learning to a degree that reversal learning could not be tested. In a hippocampal-independent two-way active avoidance task clomipramine did not have an effect on acquisition learning in QNP-treated rats; suggesting that the detrimental effect of clomipramine is hippocampus based. We also tested the effect of risperidone in QNP-sensitized animals, which is not effective in OCD treatment. Risperidone also marginally impaired acquisition learning of QNP-sensitized animals, but not reversal. Moreover, we explored the effect of the augmentation of clomipramine treatment with risperidone in QNP-sensitized rats- a common step in treating SRI unresponsive OCD patients. Only under this treatment regime animals were unimpaired in both acquisition and reversal learning. Augmentation of SRI with neuroleptics therefore could be beneficial for improving cognitive flexibility, and possibly be considered a first line of treatment in patients with reduced cognitive flexibility. PMID- 27659556 TI - Brief isoflurane anaesthesia affects differential gene expression, gene ontology and gene networks in rat brain. AB - Much is still unknown about the mechanisms of effects of even brief anaesthesia on the brain and previous studies have simply compared differential expression profiles with and without anaesthesia. We hypothesised that network analysis, in addition to the traditional differential gene expression and ontology analysis, would enable identification of the effects of anaesthesia on interactions between genes. Rats (n=10 per group) were randomised to anaesthesia with isoflurane in oxygen or oxygen only for 15min, and 6h later brains were removed. Differential gene expression and gene ontology analysis of microarray data was performed. Standard clustering techniques and principal component analysis with Bayesian rules were used along with social network analysis methods, to quantitatively model and describe the gene networks. Anaesthesia had marked effects on genes in the brain with differential regulation of 416 probe sets by at least 2 fold. Gene ontology analysis showed 23 genes were functionally related to the anaesthesia and of these, 12 were involved with neurotransmitter release, transport and secretion. Gene network analysis revealed much greater connectivity in genes from brains from anaesthetised rats compared to controls. Other importance measures were also altered after anaesthesia; median [range] closeness centrality (shortest path) was lower in anaesthetized animals (0.07 [0-0.30]) than controls (0.39 [0.30-0.53], p<0.0001) and betweenness centrality was higher (53.85 [32.56 70.00]% compared to 5.93 [0-30.65]%, p<0.0001). Simply studying the actions of individual components does not fully describe dynamic and complex systems. Network analysis allows insight into the interactions between genes after anaesthesia and suggests future targets for investigation. PMID- 27659557 TI - A simple automated system for appetitive conditioning of zebrafish in their home tanks. AB - We describe here an automated apparatus that permits rapid conditioning paradigms for zebrafish. Arduino microprocessors were used to control the delivery of auditory or visual stimuli to groups of adult or juvenile zebrafish in their home tanks in a conventional zebrafish facility. An automatic feeder dispensed precise amounts of food immediately after the conditioned stimuli, or at variable delays for controls. Responses were recorded using inexpensive cameras, with the video sequences analysed with ImageJ or Matlab. Fish showed significant conditioned responses in as few as 5 trials, learning that the conditioned stimulus was a predictor of food presentation at the water surface and at the end of the tank where the food was dispensed. Memories of these conditioned associations persisted for at least 2days after training when fish were tested either as groups or as individuals. Control fish, for which the auditory or visual stimuli were specifically unpaired with food, showed no comparable responses. This simple, low-cost, automated system permits scalable conditioning of zebrafish with minimal human intervention, greatly reducing both variability and labour intensiveness. It will be useful for studies of the neural basis of learning and memory, and for high-throughput screening of compounds modifying those processes. PMID- 27659558 TI - [Cutaneous melanocytic tumors. Pre-test]. PMID- 27659559 TI - Measuring health literacy in community agencies: a Bayesian study of the factor structure and measurement invariance of the health literacy questionnaire (HLQ). AB - BACKGROUND: The development of the Health Literacy Questionnaire (HLQ), reported in 2013, attracted widespread international interest. While the original study samples were drawn from clinical and home-based aged-care settings, the HLQ was designed for the full range of healthcare contexts including community-based health promotion and support services. We report a follow-up study of the psychometric properties of the HLQ with respondents from a diverse range of community-based organisations with the principal goal of contributing to the development of a soundly validated evidence base for its use in community health settings. METHODS: Data were provided by 813 clients of 8 community agencies in Victoria, Australia who were administered the HLQ during the needs assessment stage of the Ophelia project, a health literacy-based intervention. Most analyses were conducted using Bayesian structural equation modelling that enables rigorous analysis of data but with some relaxation of the restrictive requirements for zero cross-loadings and residual correlations of 'classical' confirmatory factor analysis. Scale homogeneity was investigated with one-factor models that allowed for the presence of small item residual correlations while discriminant validity was studied using the inter-factor correlations and factor loadings from a full 9 factor model with similar allowance for small residual correlations and cross loadings. Measurement invariance was investigated scale-by-scale using a model that required strict invariance of item factor loadings, thresholds, residual variances and co-variances. RESULTS: All HLQ scales were found to be homogenous with composite reliability ranging from 0.80 to 0.89. The factor structure of the HLQ was replicated and 6 of the 9 scales were found to exhibit clear-cut discriminant validity. With a small number of exceptions involving non-invariance of factor loadings, strict measurement invariance was established across the participating organisations and the gender, language background, age and educational level of respondents. CONCLUSIONS: The HLQ is highly reliable, even with only 4 to 6 items per scale. It provides unbiased mean estimates of group differences across key demographic indicators. While measuring relatively narrow constructs, the 9 dimensions are clearly separate and therefore provide fine grained data on the multidimensional area of health literacy. These analyses provide researchers, program managers and policymakers with a range of robust evidence by which they can make judgements about the appropriate use of the HLQ for their community-based setting. PMID- 27659560 TI - HIV-1 Tat Inhibits Autotaxin Lysophospholipase D Activity and Modulates Oligodendrocyte Differentiation. AB - White matter injury has been frequently reported in HIV+ patients. Previous studies showed that HIV-1 Tat (transactivator of transcription), a viral protein that is produced and secreted by HIV-infected cells, is toxic to young, immature oligodendrocytes (OLGs). Adding Tat to the culture medium reduced the viability of immature OLGs, and the surviving OLGs exhibited reduced process networks. OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid signaling molecule that stimulates OLG differentiation. We hypothesized that Tat affects OLG development by interfering with the ATX-LPA signaling pathway. Our data show that Tat treatment leads to changes in the expression of OLG differentiation genes and the area of OLG process networks, both of which can be rescued by LPA. Tat-treated OLGs showed no change in LPA receptor expression but significantly decreased extracellular ATX levels and lysoPLD activity. In Tat transgenic mice, expression of Tat in vivo leads to decreased OLG ATX secretion. Furthermore, co immunoprecipitation experiments revealed a potential physical interaction between Tat and ATX. Together, these data strongly suggest two functional implications of Tat blocking ATX's lysoPLD activity. On one hand, it attenuates OLG differentiation, and on the other hand it interferes with the protective effects of LPA on OLG process morphology. PMID- 27659561 TI - Surface proteins of Setaria cervi induce inflammation in macrophage through Toll like receptor 4 (TLR4)-mediated signalling pathway. AB - Lymphatic filariasis is a vectorborne parasitic disease that results in morbidities, disabilities and socio-economic loss each year globally. Inflammatory consequences associated with any form of filariasis have drawn special attention. However, the molecular insight behind the inflammation of host macrophage (MF) is considered as one of the shaded areas in filarial research. Herein, major emphasis was given to study the signalling pathway of MF inflammation induced by surface proteins (SPs) of filarial parasite through in vitro and in vivo approaches. Twenty-four hours of in vitro stimulation of Raw MFs with endotoxin-free SPs of Setaria cervi resulted in the secretion of pro inflammatory cytokines (TNF-alpha and IL-1beta) that revealed induction of inflammation, which was found to be elicited from classical NF-kB activation. Moreover, this NF-kB activation was found to be signalled from TLR4 and mediated by the downstream signalling intermediates, viz. MyD88, pTAK1 and NEMO. In vivo studies in adult Wistar rats, experimentally injected with SPs, clearly supported the outcomes of in vitro experiments by showing higher degree of inflammation rather classical activation of the peritoneal MFs. Therefore, SPs from S. cervi cuticle could be responsible for the induction of pro-inflammatory response in MF, which appears to be propagated through TLR4-NF-kB route. PMID- 27659563 TI - Contemporary Approach to Coronary Bifurcation Lesion Treatment. AB - Coronary bifurcations are frequent and account for approximately 20% of all percutaneous coronary interventions. Nonetheless, they remain one of the most challenging lesion subsets in interventional cardiology in terms of a lower procedural success rate and increased rates of long-term adverse cardiac events. Provisional side branch stenting should be the default approach in the majority of cases and we propose easily applicable and reproducible stepwise techniques associated with low risk of failure and complications. PMID- 27659562 TI - Computational Redesign of Thioredoxin Is Hypersensitive toward Minor Conformational Changes in the Backbone Template. AB - Despite the development of powerful computational tools, the full-sequence design of proteins still remains a challenging task. To investigate the limits and capabilities of computational tools, we conducted a study of the ability of the program Rosetta to predict sequences that recreate the authentic fold of thioredoxin. Focusing on the influence of conformational details in the template structures, we based our study on 8 experimentally determined template structures and generated 120 designs from each. For experimental evaluation, we chose six sequences from each of the eight templates by objective criteria. The 48 selected sequences were evaluated based on their progressive ability to (1) produce soluble protein in Escherichia coli and (2) yield stable monomeric protein, and (3) on the ability of the stable, soluble proteins to adopt the target fold. Of the 48 designs, we were able to synthesize 32, 20 of which resulted in soluble protein. Of these, only two were sufficiently stable to be purified. An X-ray crystal structure was solved for one of the designs, revealing a close resemblance to the target structure. We found a significant difference among the eight template structures to realize the above three criteria despite their high structural similarity. Thus, in order to improve the success rate of computational full-sequence design methods, we recommend that multiple template structures are used. Furthermore, this study shows that special care should be taken when optimizing the geometry of a structure prior to computational design when using a method that is based on rigid conformations. PMID- 27659565 TI - Women and Calcium: A Love-Hate Relationship at the Center of the Heart. PMID- 27659564 TI - Correlates and Impact of Coronary Artery Calcifications in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: From the Women in Innovation and Drug-Eluting Stents (WIN-DES) Collaboration. AB - OBJECTIVES: The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary intervention with drug-eluting stents (DES). BACKGROUND: The clinical correlates and the prognostic significance of CAC in women undergoing percutaneous coronary intervention with DES remain unclear. METHODS: Patient-level data from female participants in 26 randomized trials of DES were pooled. Study population was categorized according to the presence of moderate or severe versus mild or no target lesion CAC, assessed through coronary angiography. Co-primary endpoints of interest were the composite of death, myocardial infarction (MI), or target lesion revascularization and death, MI, or stent thrombosis at 3-year follow-up. RESULTS: Among 11,557 women included in the pooled dataset, CAC status was available in 6,371 women. Of these, 1,622 (25.5%) had moderate or severe CAC. In fully adjusted models, independent correlates of CAC were age, hypertension, hypercholesterolemia, smoking, previous coronary artery bypass graft surgery, and worse left ventricular and renal function. At 3 years, women with CAC were at higher risk for death, MI, or target lesion revascularization (18.2% vs. 13.1%; adjusted hazard ratio: 1.56; 95% confidence interval: 1.33 to 1.84; p < 0.0001) and death, MI, or stent thrombosis (12.7% vs. 8.6%; adjusted hazard ratio: 1.48; 95% confidence interval: 1.21 to 1.80; p = 0.0001). The adverse effect of CAC on ischemic outcomes appeared to be consistent across clinical and angiographic subsets of women, including new-generation DES. CONCLUSIONS: Women undergoing PCI of calcified lesions tend to have worse clinical profile and remain at increased ischemic risk, irrespective of new generation DES. PMID- 27659566 TI - Efficacy and Safety of Cangrelor in Preventing Periprocedural Complications in Patients With Stable Angina and Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: The CHAMPION PHOENIX Trial. AB - OBJECTIVES: The purpose of this study was to examine the safety and efficacy of cangrelor in patients with stable angina (SA) or acute coronary syndrome (ACS). BACKGROUND: The CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) trial demonstrated that cangrelor significantly reduced periprocedural ischemic events in all-comer percutaneous coronary intervention with a modest increase in mild and moderate bleeding. Whether this benefit is consistent across SA and ACS has not been explored fully. METHODS: The CHAMPION PHOENIX trial compared periprocedural administration of cangrelor or clopidogrel, with either a 300- or 600-mg loading dose for the prevention of periprocedural complications in patients undergoing percutaneous coronary intervention. Among the 10,942 patients in the modified intention to treat population, 6,358 patients were classified as having SA, and 4,584 patients had ACS (including unstable angina, non ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction) at randomization. The primary composite endpoint was death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h. A key secondary endpoint was stent thrombosis, and the primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) severe bleeding. RESULTS: Cangrelor consistently reduced the primary endpoint in SA and ACS (odds ratio [OR]: 0.83 [95% confidence interval (CI): 0.67 to 1.01] and OR: 0.71 [95% CI: 0.52 to 0.96], respectively; interaction p = 0.41). Cangrelor also consistently reduced stent thrombosis in SA and ACS (OR: 0.55 [95% CI: 0.30 to 1.01] and OR: 0.67 [95% CI: 0.42 to 1.06], respectively; interaction p = 0.62). The impact of cangrelor on GUSTO severe/moderate bleeding was also similar for SA and ACS (OR: 1.49 [95% CI: 0.67 to 3.33] and OR: 1.79 [95% CI: 0.79 to 4.07], respectively; interaction p = 0.75). CONCLUSIONS: The benefits and risks of cangrelor were consistent in patients with SA and ACS. (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]; NCT01156571). PMID- 27659567 TI - Cangrelor: Fixing Life or Just a Leak? PMID- 27659569 TI - Only the Slipperiest Can Escape From Jail Unscathed. PMID- 27659568 TI - Structural Damage of Jailed Guidewire During the Treatment of Coronary Bifurcation Lesions: A Microscopic Randomized Trial. AB - OBJECTIVES: The study sought to compare the safety (resistance to damage) and efficacy (ability to cross the side branch) of polymer-coated and non-polymer coated guidewires in the jailed wire technique used during the percutaneous treatment of bifurcation lesions. BACKGROUND: The jailed wire technique is a useful strategy in the treatment of bifurcation lesions by provisional stenting. However, these wires can be damaged or even be broken during their removal. METHODS: We performed a randomized study in patients with bifurcation lesions treated by provisional stenting. The jailed wire technique was mandatory, and the types of guidewires, polymer-coated (n = 115) and non-polymer-coated (n = 120), were randomized. After the procedures, the wires were evaluated by stereoscopic microscopy. The induced damage in the wires was classified as follows: no damage, mild, moderate, or severe. RESULTS: The clinical characteristics were similar between patients treated with polymer-coated or non-polymer-coated wires. Polymer coated wires were significantly (p < 0.001) more resistant to retrieval damage (only 2 wires showed mild damage) than were non-polymer-coated wires. However, 63 (55%) of the non-polymer-coated wires were damaged; 37 (32%), 24 (21%), and 2 (2%) had mild, moderate, and severe damage, respectively. Additionally, the jailed length of the wire was a factor contributing to the degree of wire damage. The time of side branch wiring was shorter in the polymer-coated wire group (19 +/- 40 s vs. 42 +/- 72 s; p < 0.05). CONCLUSIONS: Jailed wires during interventional procedures of bifurcation lesions commonly showed microscopic damage. Polymer-coated wires were more resistant to retrieval damage and were more efficient in crossing the side branch ostium than non-polymer-coated wires. (Jailed Wire Technique in the Treatment of Coronary Bifurcations Lesions With Stent: Stereoscopic Microscopy Study; NCT02516891). PMID- 27659570 TI - Percutaneous Intervention to Treat Platypnea-Orthodeoxia Syndrome: The Toronto Experience. AB - OBJECTIVES: This study reviewed a series of patients treated with transcatheter closure of septal defect to treat platypnea-orthodeoxia syndrome, with specific attention to septal characteristics and device choice. BACKGROUND: Platypnea orthodeoxia syndrome is an uncommon condition characterized by positional dyspnea and hypoxemia due to intracardiac right-to-left shunting through a patent foramen ovale (PFO), an atrial septal defect, or pulmonary arteriovenous malformations. Percutaneous closure of such defects is the treatment of choice. METHODS: In this single-center series, 52 patients were treated with percutaneous closure of an interatrial communication after presentation between January 1997 and July 2015. Septal morphology, clinical, procedural, and outcomes data were analyzed. RESULTS: All patients had a PFO; however, nearly one-quarter required a non-PFO device (11 Amplatzer Septal Occluder and 1 post-infarct muscular VSD), as opposed to a dedicated PFO device to achieve shunt occlusion. These patients were characterized by an aneurysmal septum, shorter primum septum overlap with the secundum septum, and greater septal angulation from the midline. After closure, all demonstrated acute improvements in oxygen saturation (pre-procedure: 81 +/- 8%; post-procedure: 95.1 +/- 0.5% on room air). Each patient was treated with a single device and no one required re-intervention. CONCLUSIONS: Patients presenting with platypnea-orthodeoxia syndrome can be treated successfully with a percutaneous intervention often requiring a variety of devices. Those requiring a non-PFO-type device had a greater prevalence of an aneurysmal septum, shorter primum septal overlap with the secundum septum, and greater septal angulation with the midline. PMID- 27659571 TI - Platypnea-Orthodeoxia Syndrome: An Overlooked Cause of Hypoxemia. PMID- 27659572 TI - Acotec Drug-Coated Balloon Catheter: Randomized, Multicenter, Controlled Clinical Study in Femoropopliteal Arteries: Evidence From the AcoArt I Trial. AB - OBJECTIVES: The aim of this study was to investigate the efficacy and safety of a new paclitaxel-coated balloon catheter in the treatment of stenotic or occluded femoropopliteal arteries. BACKGROUND: The incidence of restenosis can be reduced by the use of drug-coated balloons. However, dose, coating composition, and technology are decisive for efficacy. METHODS: Two hundred Chinese patients with peripheral arterial occlusive disease were prospectively randomized to treatment with new paclitaxel-coated or standard uncoated balloon catheters. The primary endpoint was angiographic late lumen loss at 6 months, measured by a blinded core laboratory. Secondary angiographic endpoints (6 months) and specific clinical endpoints (1 year) were binary restenosis, ankle-brachial index, Rutherford stage, clinically driven target lesion revascularization, and amputation. RESULTS: Patients' mean age was 66 years, 74% were men, 31% were smokers, and 55% had diabetes. Patients were in Rutherford stages 2 through 5, with a mean lesion length of 150 mm; 25% had in-stent restenosis, 55% had occlusion or partial occlusion, and 20% underwent provisional stenting. Late lumen loss at 6 months was available for 89%, and clinical follow-up was available for >95% per group. Mean late lumen loss was 0.05 +/- 0.73 mm with coated balloons and 1.15 +/- 0.89 mm with uncoated balloons (p < 0.001). Correspondingly, the rates of restenosis were 22.5% and 70.8% (p < 0.001). After 1 year, the rates of target lesion revascularization were 7.2% and 39.6% (p < 0.001), and Rutherford class and ankle brachial index improved more markedly in the coated group (p < 0.046 and p = 0.023, respectively). One major amputation was recorded in the control group. No coating-related adverse events were observed for doses of up to 43 mg paclitaxel per patient. CONCLUSIONS: In this medium-sized trial with long superficial femoral artery lesions, the use of paclitaxel-coated balloon catheters markedly improved angiographic and clinical outcomes of interventions despite advanced disease in the majority of patients. PMID- 27659573 TI - Drug-Coated Balloon in Complex Clinical and Anatomical Scenario: Evidence or Hope? PMID- 27659575 TI - Predictors of Bioresorbable Everolimus-Eluting Scaffold Failure at Intravascular Ultrasound Examination: Asymmetry Versus Expansion. PMID- 27659574 TI - Elimination of Transcoarctation Pressure Gradients Has No Impact on Left Ventricular Function or Aortic Shear Stress After Intervention in Patients With Mild Coarctation. AB - OBJECTIVES: This study sought to investigate the impact of transcatheter intervention on left ventricular function and aortic hemodynamics in patients with mild coarctation of the aorta (COA). BACKGROUND: The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak transcoarctation pressure gradient <20 mm Hg). Debate rages regarding the risk/benefit ratio of intervention versus long term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function, and peripheral perfusion. METHODS: We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (before and after intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the left ventricle in 34 patients with mild COA to make these correlations. RESULTS: Despite dramatic reduction in the transcoarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced by 75% and 47.3%, respectively), there was only modest effect on aortic flow and no significant impact on aortic shear stress (the maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve left ventricular function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%, respectively). CONCLUSIONS: Transcatheter intervention that successfully relieves mild COA pressure gradients does not translate to decreased myocardial strain. The effects of the intervention were determined to the greatest degree by ventricular vascular coupling hemodynamics and provide a novel valuable mechanism to evaluate patients with COA that may influence clinical practice. PMID- 27659576 TI - Reply: Predictors of Bioresorbable Everolimus-Eluting Scaffold Failure at Intravascular Ultrasound Examination: Asymmetry Versus Expansion. PMID- 27659577 TI - The Hidden Players. PMID- 27659578 TI - Optimal Medical Therapy in the Prognosis of Coronary Artery Disease. PMID- 27659579 TI - Reply: The Hidden Players. PMID- 27659580 TI - Reply: Optimal Medical Therapy in the Prognosis of Coronary Artery Disease. PMID- 27659581 TI - When to Choose the Road Less Traveled. PMID- 27659582 TI - Beyond The Anticipatory Corpse: Medicine, Power, and the Care of the Dying: A Theoretical and Methodological Intervention into the Sociology of Brain Implant Surgery. AB - Drawing on and extending the Foucaultian philosophical framework that Jeffrey Bishop develops in his masterful book, The Anticipatory Corpse: Medicine, Power, and the Care of the Dying, we undertake a sociological analysis of the neurological procedure-deep brain stimulation (DBS)-which implants electrodes in the brain, powered by a pacemaker-like device, for the treatment of movement disorders. Following Bishop's work, we carry out this analysis through a two-fold strategy. First, we examine how a multidisciplinary team evaluates candidates for this implant at a major medical center. We present excerpts from an ethnographic study of the "case conference" where disease entities are presented, contested, ratified, and made objects for intervention with this technology. The case conference becomes the key site in the transition from "person-with-illness" to "person-with-brain-implant" as a team of health professionals determines a plan of action by interpreting both statistical and "quality of life" data regarding their patients. Second, this article explores these decision-making processes through Bishop's conceptualization of evidence-based medicine, which relies on statistical approaches as the ultimate authority in knowledge production and medical decisions. We then reflect on Bishop's critique of the social sciences and the methodological, analytical, and substantive ramifications that The Anticipatory Corpse can offer future sociological work. PMID- 27659583 TI - Good Deaths, "Stupid Deaths": Humane Medicine and the Call of Invisible Bodies. AB - Jeffrey Bishop's The Anticipatory Corpse exposes a functional metaphysics at the root of contemporary medical practice that gives rise to inhumane medicine, especially at the end of life. His critique of medicine argues for alternative spaces and practices in which the communal significance of the body, its telos, can be restored and the meaning of a "good death" enriched. This essay develops an alternative epistemology of the body, drawing from Christian theological accounts of the communal or Eucharistic body and linking liturgical practices to the cultivation of solidarity. It argues for an epistemology of the body that makes visible the invisible bodies at medicine's margins and illumines the disparate worlds of health care globally. PMID- 27659584 TI - Prevalence and trends of leisure-time physical activity by occupation and industry in U.S. workers: the National Health Interview Survey 2004-2014. AB - PURPOSE: Studies describing prevalence and trends of physical activity among workers in the United States are scarce. We aimed to estimate prevalence and trends of "sufficient" leisure-time physical activity (LTPA) during the 2004-2014 time period among U.S. workers. METHODS: Data were collected for U.S. workers in the National Health Interview Survey. LTPA was categorized as sufficiently active (moderate intensity, >=150 minutes per week), insufficiently active (10-149 minutes per week), and inactive (<10 minutes per week). Prevalence of LTPA was adjusted for age using 2010 U.S. working population as a standardized age distribution. RESULTS: Prevalence trends of "sufficient" LTPA significantly increased from 2004 to 2014 (45.6% to 54.8%; P < .001). Among industry groups, the highest prevalence of "sufficient" LTPA was observed among workers in Professional/Scientific/Technical Services (62.1%). The largest increases were observed among workers in Public Administration (51.3%-63.4%). Among occupational groups, "sufficient" LTPA prevalence was lowest in farming/fishing/forestry (30.8%) and highest in life/physical/social science (66.4%). Prevalence of LTPA significantly increased from 2004 to 2014 in most occupational and industry groups. CONCLUSIONS: Among U.S. workers, trends of "sufficient" LTPA significantly increased between 2004 and 2014. Overall, a larger proportion of white-collar compared to blue-collar workers were engaged in "sufficient" LTPA. PMID- 27659585 TI - An argument for renewed focus on epidemiology for public health. AB - PURPOSE: Although epidemiology has an indispensable role in serving public health, the relative emphasis of applications of epidemiology often tend toward individual-level medicine over public health in terms of resources and impact. METHODS: We make distinctions between public health and medical applications of epidemiology to raise awareness among epidemiologists, many of whom came to the field with public health in mind. We discuss reasons for the overemphasis on medical epidemiology and suggest ways to counteract these incentives. RESULTS: Public health epidemiology informs interventions that are applied to populations or that confer benefits beyond the individual, whereas medical epidemiology informs interventions that improve the health of treated individuals. Available resources, new biomedical technologies, and existing epidemiologic methods favor medical applications of epidemiology. Focus on public health impact and methods suited to answer public health questions can create better balance and promote population-level improvements in public health. CONCLUSIONS: By deliberately reflecting on research motivations and long-term goals, we hope the distinctions presented here will facilitate critical discussion and a greater consciousness of our potential impact on both individual and population-level health. Renewed intentions towards public health can help epidemiologists navigate potential projects and ultimately contribute to an epidemiology of consequence. PMID- 27659588 TI - From CRNE to NCLEX-RN: musings on nursing and the idea of a national final examination. PMID- 27659586 TI - Disease-related mortality among 21,609 Norwegian male military peacekeepers deployed to Lebanon between 1978 and 1998. AB - PURPOSE: Our study assessed disease-related mortality among Norwegian male military peacekeepers deployed to Lebanon during 1978-1998. METHODS: A total of 21,609 peacekeepers were followed from start of deployment through 2013. Standardized mortality ratios (SMRs) were calculated based on national rates for the overall cohort, by length of time since first deployment to Lebanon, and for service during high- and low-conflict periods. Poisson regression was used to determine the effect of conflict exposure. RESULTS: In the overall cohort, a decreased risk was seen for all-cause mortality (1213 deaths, SMR = 0.85), mortality from neoplasms (SMR = 0.89), and from non-neoplastic diseases (SMR = 0.68). Disease-related mortality was lower during the first 5 years of follow-up, while mortality from external causes was elevated. After 5 years, mortality from neoplasms and external causes were similar to national rates, but mortality from non-neoplastic diseases remained lower. The high-conflict exposure group had a two-fold increased risk of mortality from non-neoplastic diseases (rate ratio = 2.33), including ischemic heart disease (rate ratio = 2.25) compared to the low conflict exposure group. CONCLUSIONS: We found a "healthy soldier effect" for all cause mortality and disease-related mortality, but for neoplasms, this effect disappeared after 5 years. Conflict exposure was positively correlated with increased risk of mortality from non-neoplastic diseases. PMID- 27659587 TI - Delineation of body mass index trajectory predicting lowest risk of mortality in U.S. men using generalized additive mixed model. AB - PURPOSE: Few studies have delineated body mass index (BMI) trajectories that associate with premature mortality, which is defined as death occurring before age 75 years. METHODS: We used generalized additive mixed model to identify BMI trajectories of individuals dying before or after age 75 years among 14,172 U.S. men. We used logistic regression to validate whether the BMI trajectory developed predicted mortality in an independent cohort of 7000 participants. RESULTS: Comparing to participants with age at death less than 75 years, the BMI among participants with age at death 75 years or more was lower throughout adulthood, and the mean BMI was 23.98, 24.63, 25.33, and 25.29 kg/m2 at age 40, 50, 60, and 70 years. In the validation cohort, participants following the BMI trajectory with age at death less than 75 years had higher risks of total mortality (odds ratio: 1.35; 95% confidence interval: 1.01-1.78) and cardiovascular disease mortality (1.92; 1.10-3.35) compared to participants following the trajectory with age at death 75 years or more. Participants whose BMI trajectories diverged the most from the trajectory with age at death 75 years or more had highest risks of total mortality (1.72; 1.23-2.40) and cardiovascular disease mortality (3.06; 1.49-6.30). CONCLUSIONS: Individual is suggested to maintain a normal BMI throughout adulthood to have greater longevity. PMID- 27659589 TI - Reconciling concepts of time and person-centred care of the older person with cognitive impairment in the acute care setting. AB - The aim of this analysis was to examine the concept of time to rejuvenate and extend existing narratives of time within the nursing literature. In particular, we hope to promote a new trajectory in nursing research and practice which focuses on time and person-centred care, specifically of older people with cognitive impairment hospitalized in the acute care setting. We consider the explanatory power of concepts such as clock time, process time, fast care, slow care and time debt for elucidating the relationship between 'good care' and 'time use'. We conclude by offering two additional concepts of time, plurotemporality and person-centred time (PCT) which we propose will help advance of nursing knowledge and practice. Nurse clinicians and researchers can use these alternative concepts of time to explore and describe different temporal structures that honour the patient's values and preferences using experiential, observation-based nursing research approaches. PMID- 27659591 TI - Nonplanar Butterfly-Shaped pi-Expanded Pyrrolopyrroles. AB - Large aza-analogues of curved polycyclic aromatic hydrocarbons with a double helicene structure present unique features for molecular photonics. We present the preparation and characterization of three such structures. The synthesis of these heterocyclic nanographenes involves only a few high-yield steps that use readily available starting materials. X-ray analysis revealed that each of these new dyes has three conformational isomers: one diastereoisomer in a meso form and two enantiomers in twisted forms [(P,P)] and [(M,M)]. The low energy barriers between the conformers, however, prevent their separation by using chiral HPLC, and the NMR spectra show only one set of signals for each of these curved compounds. Density functional theory (DFT) calculations quantify the small energy difference and the small energy barriers between the chiral and meso forms, which fully supports the experimental results. Their optical absorption lacks any sensitivity to the solvent environment, whereas their fluorescence features exhibit pronounced solvatochromism. This rarely observed solvatofluorochromism of centrosymmetric molecules without either electron-withdrawing groups or -donating substituents was probed by using time-resolved spectroscopy. These studies suggest that, similar to 9,9'-bianthryl, the nonpolar locally excited state shows negligible solvatochromism, whereas the charge-transfer state is sensitive to solvent polarity. PMID- 27659592 TI - Exploring the evolutionary origins of overimitation: a comparison across domesticated and non-domesticated canids. AB - When learning from others, human children tend to faithfully copy - or 'overimitate' - the actions of a demonstrator, even when these actions are irrelevant for solving the task at hand. We investigate whether domesticated dogs (Canis familiaris) and dingoes (Canis dingo) share this tendency to overimitate in three experiments. In Experiment 1, dogs and dingoes had the opportunity to solve a puzzle after watching an ostensive demonstrator who used both a relevant action and an irrelevant action. We find clear evidence against overimitation in both species. In contrast to human children (Horner & Whiten, 2005), dogs and dingoes used the irrelevant action less often across trials, suggesting that both species were filtering out the irrelevant action as they gained experience with the puzzle (like chimpanzees; Horner & Whiten, 2005). Experiments 2 and 3 provide further evidence against overimitation, demonstrating that both species' behavior is better characterized by individual exploration than overimitation. Given that both species, particularly dogs, show human-like social learning in other contexts, these findings provide additional evidence that overimitation may be a unique aspect of human social learning. A video abstract of this article can be viewed at: https://youtu.be/g2mRniJZ7aU. PMID- 27659593 TI - Biosynthesis of catechol melanin from glycerol employing metabolically engineered Escherichia coli. AB - BACKGROUND: Melanins comprise a chemically-diverse group of polymeric pigments whose function is related to protection against physical and chemical stress factors. These polymers have current and potential applications in the chemical, medical, electronics and materials industries. The biotechnological production of melanins offers the possibility of obtaining these pigments in pure form and relatively low cost. In this study, Escherichia coli strains were engineered to evaluate the production of melanin from supplemented catechol or from glycerol derived catechol produced by an Escherichia coli strain generated by metabolic engineering. RESULTS: It was determined that an improved mutant version of the tyrosinase from Rhizobium etli (MutmelA), could employ catechol as a substrate to generate melanin. Strain E. coli W3110 expressing MutmelA was grown in bioreactor batch cultures with catechol supplemented in the medium. Under these conditions, 0.29 g/L of catechol melanin were produced. A strain with the capacity to synthesize catechol melanin from a simple carbon source was generated by integrating the gene MutmelA into the chromosome of E. coli W3110 trpD9923, that has been modified to produce catechol by the expression of genes encoding a feedback inhibition resistant version of 3-deoxy-D-arabino-heptulosonate 7 phosphate synthase, transketolase and anthranilate 1,2-dioxygenase from Pseudomonas aeruginosa PAO1. In batch cultures with this strain employing complex medium with 40 g/L glycerol as a carbon source, 1.21 g/L of catechol melanin were produced. The melanin was analysed by employing Fourier transform infrared spectroscopy, revealing the expected characteristics for a catechol-derived polymer. CONCLUSIONS: This constitutes the first report of an engineered E. coli strain and a fermentation process for producing a catechol melanin from a simple carbon source (glycerol) at gram level, opening the possibility of generating a large quantity of this polymer for its detailed characterization and the development of novel applications. PMID- 27659595 TI - HOMEODOMAIN PROTEIN 1 is required for jasmonate-mediated glandular trichome initiation in Artemisia annua. AB - Glandular trichomes are generally considered biofactories that produce valuable chemicals. Increasing glandular trichome density is a very suitable way to improve the productivity of these valuable metabolites, but little is known about the regulation of glandular trichome formation. Phytohormone jasmonate (JA) promotes glandular trichome initiation in various plants, but its mechanism is also unknown. By searching transcription factors regulated by JA in Artemisia annua, we identified a novel homeodomain-leucine zipper transcription factor, HOMEODOMAIN PROTEIN 1 (AaHD1), which positively controls both glandular and nonglandular trichome initiations. Overexpression of AaHD1 in A. annua significantly increased glandular trichome density without harming plant growth. Consequently, the artemisinin content was improved. AaHD1 interacts with A. annua jasmonate ZIM-domain 8 (AaJAZ8), which is a repressor of JA, thereby resulting in decreased transcriptional activity. AaHD1 knockdown lines show decreased sensitivity to JA on glandular trichome initiation, which indicates that AaHD1 plays an important role in JA-mediated glandular trichome initiation. We identified a new transcription factor that promotes A. annua glandular trichome initiation and revealed a novel molecular mechanism by which a homeodomain protein transduces JA signal to promote glandular trichome initiation. Our results also suggested a connection between glandular and nonglandular trichome formations. PMID- 27659594 TI - The natural plant stress elicitor cis-jasmone causes cultivar-dependent reduction in growth of the stink bug, Euschistus heros and associated changes in flavonoid concentrations in soybean, Glycine max. AB - To test the hypothesis that the plant stress related elicitor cis-jasmone (cJ) provides protection in soybean pods against the seed-sucking stink bug pest, Euschistus heros, the growth of E. heros on cJ-treated pods was investigated using three soybean cultivars differing in insect susceptibility, i.e. BRS 134 (susceptible), IAC 100 (resistant) and Dowling (resistant). E. heros showed reduced weight gain when fed cJ-treated Dowling, whereas no effect on weight gain was observed when fed other treated cultivars. Using analysis of variance, a three factor (cultivar x treatment x time) interaction was observed with concentrations of the flavonoid glycosides daidzin and genistin, and their corresponding aglycones, daidzein and genistein. There were increases in genistein and genistin concentrations in cJ-treated Dowling at 144 and 120 h post treatment, respectively. Higher concentrations of malonyldaidzin and malonylgenistin in Dowling, compared to BRS 134 and IAC 100, were observed independently of time, the highest concentrations being observed in cJ-treated seeds. Levels of glycitin and malonylglycitin were higher in BRS 134 and IAC 100 compared to Dowling. Canonical variate analysis indicated daidzein (in the first two canonical variates) and genistein (in the first only) as important discriminatory variables. These results suggest that cJ treatment leads to an increase in the levels of potentially defensive isoflavonoids in immature soybean seeds, but the negative effect upon E. heros performance is cultivar-dependent. PMID- 27659596 TI - Measuring Error Identification and Recovery Skills in Surgical Residents. AB - BACKGROUND: Although error identification and recovery skills are essential for the safe practice of surgery, they have not traditionally been taught or evaluated in residency training. This study validates a method for assessing error identification and recovery skills in surgical residents using a thoracoscopic lobectomy simulator. METHODS: We developed a 5-station, simulator based examination containing the most commonly encountered cognitive and technical errors occurring during division of the superior pulmonary vein for left upper lobectomy. Successful completion of each station requires identification and correction of these errors. Examinations were video recorded and scored in a blinded fashion using an examination-specific rating instrument evaluating task performance as well as error identification and recovery skills. Evidence of validity was collected in the categories of content, response process, internal structure, and relationship to other variables. RESULTS: Fifteen general surgical residents (9 interns and 6 third-year residents) completed the examination. Interrater reliability was high, with an intraclass correlation coefficient of 0.78 between 4 trained raters. Station scores ranged from 64% to 84% correct. All stations adequately discriminated between high- and low-performing residents, with discrimination ranging from 0.35 to 0.65. The overall examination score was significantly higher for intermediate residents than for interns (mean, 74 versus 64 of 90 possible; p = 0.03). CONCLUSIONS: The described simulator-based examination with embedded errors and its accompanying assessment tool can be used to measure error identification and recovery skills in surgical residents. This examination provides a valid method for comparing teaching strategies designed to improve error recognition and recovery to enhance patient safety. PMID- 27659597 TI - Bilateral Internal Thoracic Artery Grafting Increases Mediastinitis: Myth or Fact? AB - BACKGROUND: There is controversy about the risk of mediastinitis associated with the use of both internal thoracic arteries (ITA). METHODS: We performed a case control study of patients operated on at a single institution from January 2003 to December 2014. A total of 3,118 consecutive patients undergoing isolated coronary artery bypass graft surgery were included; 81.3% (n = 2,533) underwent bilateral ITA (BITA) grafts exclusively and constitute the BITA group, and 18.7% (n = 585) constitute the single ITA (SITA) group. Mediastinitis was defined as deep tissue mediastinal infection, with clinical or microbiologic evidence. Continuous variables were expressed as mean +/- SD, and categoric variables as percentage (range). Student's t test and Fisher's exact test were used, as appropriate. Propensity score matching analysis was performed according to the nearest neighbor estimation method (n = 1,040). RESULTS: The incidence of diabetes mellitus was similar in both groups (29%, p = 0.9). The BITA patients were more like to be younger (p < 0.001), men (p < 0.001), had a higher prevalence of hypertension (p < 0.01), higher body mass index (p < 0.001), lower prevalence of left ventricular dysfunction (p < 0.001) and of previous myocardial infarction (p < 0.01), and greater use of off-pump coronary artery bypass graft surgery (p < 0.01). The BITA patients had lower unadjusted hospital mortality (1.6%, versus 5.3% for SITA, p < 0.0001). The total incidence of mediastinitis was 1.8% (BITA 1.9% versus SITA 1.5%, p = 0.6). Diabetes (p < 0.01) and nonelective surgery (p = 0.004) were the only predictors of mediastinitis in the entire population. Propensity score matching showed no differences in mediastinitis: BITA 2.5% versus SITA 1.3% (p = 0.17). CONCLUSIONS: In this series of patients, BITA did not increase the risk of mediastinitis in the total population or in the propensity score matched subgroups. PMID- 27659598 TI - Body Mass Index and Total Psoas Area Affect Outcomes in Patients Undergoing Pneumonectomy for Cancer. AB - BACKGROUND: Hypothesizing that morphometric measurements are reliable markers of fitness in patients with lung cancer requiring aggressive surgical intervention, the purpose of this study was to assess their impact on postoperative outcome and long-term survival in patients with non-small cell lung cancer (NSCLC) requiring pneumonectomy. METHODS: Height, weight, and body mass index (BMI), as well as usual clinical, laboratory (including C-reactive protein [CRP] concentrations), and pathologic data were retrospectively retrieved from files of 161 consecutive patients treated by pneumonectomy for NSCLC, whose preoperative computed tomographic (CT) scans were available in the Picture Archive and Communication System (PACS) of the hospital. Cross-sectional areas of right and left psoas areas (measured by CT scan at the L3 level), perirenal fat thickness, and anterior subcutaneous tissue thickness at the left renal vein level were also assessed. RESULTS: BMI and total psoas area were strongly and directly correlated (p = 0.0000001), whereas BMI was inversely related to CRP levels. Sarcopenia (total psoas area <=33rd percentile) was associated with high CRP levels (>20 mg/L) (p = 0.010). Factors associated with 90-day mortality included older age (p = 0.000045), lower body weight (p = 0.032), and BMI less than or equal to 25 kg/m2 (p = 0.013). At univariate analysis, long-term outcome was negatively affected by a nonsquamous cell histologic type (p = 0.011), pathologic stage IIIB IV (p =0.026), CRP levels greater than 20 mg/L (p = 0.017), BMI less than or equal to 25 kg/m2 (p = 0.010), and total psoas area less than or equal to the 33rd percentile (p = 0.029). Multivariate analysis showed the independent prognostic value of both BMI and total psoas area. CONCLUSIONS: BMI less than or equal to 25 kg/m2 and total psoas cross-sectional area less than or equal to the 33rd percentile are prognostic determinants in patients with NSCLC requiring pneumonectomy. PMID- 27659599 TI - Surgically Corrected Mitral Regurgitation During Left Ventricular Assist Device Implantation Is Associated With Low Recurrence Rate and Improved Midterm Survival. AB - BACKGROUND: Indications for concomitant intervention for mitral regurgitation (MR) during left ventricular assist device (LVAD) implantation remain controversial. The objective of this study was to determine the impact of the surgical correction of MR during LVAD implantation. METHODS: From July 2008 to December 2014, 164 patients with significant preoperative MR underwent LVAD (HeartMate II; Thoratec, Pleasanton, CA) implantation. The MR resolved after LVAD implantation in 110 of 164 patients (67.1%) with either surgical or spontaneous correction. The cohort (n = 110) without significant postoperative MR was divided into two groups: a spontaneous correction group (n = 54, MR spontaneously resolved after LVAD implantation); and a surgical correction group (n = 56, MR surgically corrected). Patients who received aortic valve procedures (n = 17) were excluded from this study. RESULTS: Patient demographics, perioperative outcomes including bleeding, prolonged intubation, and stroke, and inhospital mortality did not differ in the two groups except for significantly longer cardiopulmonary bypass time in the surgical correction group (spontaneous correction 123 minutes [interquartile range (IQR): 107 to 150] versus surgical correction 177 minutes [IQR: 132 to 198], p < 0.001). During follow-up, pulmonary wedge pressure (spontaneous correction 17 mm Hg [IQR: 12 to 23 mm Hg] versus surgical correction 12 mm Hg [IQR: 4 to 17 mm Hg], p = 0.015) and pulmonary vascular resistance (spontaneous correction 2.0 Wood units [IQR: 1.5 to 2.4] versus surgical correction 1.7 Wood units [IQR: 0.8 to 2.1], p = 0.047) were significantly improved in the surgical correction group compared with the spontaneous correction group. Overall survival rate and freedom from recurrent MR were significantly better in the surgical correction group compared with the spontaneous correction group (1-year survival, spontaneous correction 59.4% +/- 6.9% versus surgical correction 69.6% +/- 6.4%, log rank p = 0.030; 1-year freedom from recurrent MR, spontaneous correction 76.2% +/- 7.5% versus surgical correction 95.0% +/- 3.5%, log rank p = 0.028). CONCLUSIONS: The LVAD patients with surgically corrected MR had improved midterm hemodynamics and survival compared with spontaneously resolved MR, along with low recurrence of MR. Aggressive surgical mitral valve intervention during LVAD implantation may be recommended. PMID- 27659600 TI - Process Improvement in Thoracic Donor Organ Procurement: Implementation of a Donor Assessment Checklist. AB - BACKGROUND: Donor organs are often procured by junior staff in stressful, unfamiliar environments where a single adverse event can be catastrophic. A formalized checklist focused on preprocedural processes related to thoracic donor organ procurement could improve detection and prevention of near miss events. METHODS: A checklist was developed centered on patient identifiers, organ compatibility and quality, and team readiness. It went through five cycles of feedback and revision using a panel of expert procurement surgeons. Educational in-service sessions were held on the use of the checklist as well as best organ assessment practices. Near miss events before the survey were tallied by retrospective review of 20 procurements, and near misses after checklist implementation were prospectively recorded. We implemented the checklist for 40 donor lung and heart procurements: 20 from Cleveland Clinic and 20 from the University of Minnesota. A final survey assessment was used to determine ease of use. RESULTS: Nine near miss events were reported in 20 procurements before use of the checklist. Thirty-one near miss events of 40 organ procurements were identified and potentially prevented by the checklist. Eighty-seven percent of fellows found the checklist to be unobtrusive to work flow, and 100% believed its use should be mandatory. Mortality was the same before and after implementation of the checklist despite increased patient volumes. CONCLUSIONS: Implementation of a simple checklist for use during thoracic organ procurement uncovered a substantial number of near miss events. A preprocedural checklist for all thoracic organ transplants in the United States and abroad is feasible and would likely reduce adverse events. PMID- 27659601 TI - Totally Endoscopic (VATS) First Rib Resection for Thoracic Outlet Syndrome. AB - BACKGROUND: Thoracic outlet syndrome (TOS) causes neurologic symptoms in 95% of cases and vascular symptoms in 5% of cases. Surgical resection is curative. Endoscopic-assisted transaxillary first rib resection has been previously reported. In this study we report a totally endoscopic video-assisted thoracoscopic surgery (VATS) approach using tailored endoscopic instruments. METHODS: Ten patients (8 women; average age, 32.3 +/- 5.6 years) with TOS underwent VATS first rib resection following failure of symptom improvement with physiotherapy. Symptoms were: unilateral neurogenic (n = = 7), bilateral neurogenic (n = = 2), and bilateral arterial compression (n = = 1). Three standard VATS ports were utilized. The parietal pleura and periosteum overlying the first rib were stripped avoiding injury to the neurovascular bundle. The rib was transected with an endoscopic rib cutter and resected completely in a piecemeal fashion using endoscopic bone nibblers. All periosteal remnants were trimmed releasing the neurovascular bundle completely. RESULTS: Patients were discharged within 72 hours following surgery. One patient had the contralateral side treated 18 months later and another patient is awaiting the second surgery. At follow-up, 9 patients had complete resolution of their main symptoms. One patient with neurogenic TOS developed mild functional and sensational loss of the non-dominant hand that improved within 8 months with physiotherapy. CONCLUSIONS: VATS first rib resection for TOS provides, unlike the classic approaches, a superior, magnified, and well-illuminated view of the thoracic inlet. It allows good posterior trimming of the first rib, release of brachial plexus, and an aesthetically pleasing result, especially in female patients. PMID- 27659603 TI - Bioassay-guided isolation of an active compound with protein tyrosine phosphatase 1B inhibitory activity from Sargassum fusiforme by high-speed counter-current chromatography. AB - A rapid and efficient method using high-speed counter-current chromatography was established for the bioassay-guided separation of an active compound with protein tyrosine phosphatase 1B inhibitory activity from Sargassum fusiforme. Under the bioassay guidance, the ethyl acetate extract with the best IC50 value of 0.37 +/- 0.07 MUg/mL exhibited a potential protein tyrosine phosphatase 1B inhibitory activity, which was further separated by high-speed counter-current chromatography. The separation was performed with a two-phase solvent system composed of n-hexane/methanol/water (5:4:1, v/v). As a result, dibutyl phthalate (19.7 mg) with the purity of 95.3% was obtained from 200 mg of the ethyl acetate extract. Its IC50 was 14.05 +/- 0.06 MUM, which was further explained by molecular docking. The result of molecular docking showed that dibutyl phthalate enfolded in the catalytic site of protein tyrosine phosphatase 1B. The main force between dibutyl phthalate and protein tyrosine phosphatase 1B was the hydrogen bond interaction with Gln266. In addition, hydrogen bond, van der Waals force and hydrophobic interaction with the amino acids (Ala217, Ile219, and Gly220) were also responsible for the stable protein-ligand complex. PMID- 27659602 TI - The Aortic Root: Natural History After Root-Sparing Ascending Replacement in Nonsyndromic Aneurysmal Patients. AB - BACKGROUND: Leaving native aortic tissue in situ in root-sparing ascending aortic replacement raises concern regarding potential later need for root reoperation or for the potential occurrence of localized dissections or rupture in the residual root. The purpose of this study was to evaluate the natural growth of the aortic root after root-sparing aortic replacement. METHODS: In all, 102 consecutive patients (mean age 61.8 +/- 12.5 years; 60% male) who had undergone root-sparing aortic replacement had sufficient retrievable information regarding their aortic root diameter at postoperative baseline and follow-up imaging by computed tomography or echocardiography. The annual growth rate was evaluated and also compared according to the influence of valve morphology and concomitant aortic valve replacement. Furthermore, the years of natural history that would require for root enlargement to meet a 50 mm threshold of the root diameter were calculated. RESULTS: The estimated growth rate of the aortic root after root sparing aortic replacement is between 0.27 and 0.51 mm per year (mean 0.41 mm, varying according to the underlying diameter) and therefore fivefold less than other aortic regions. Accordingly, a root aneurysm indicating reoperation would not be expected for 29.1 years on average. Only patients with a diameter of 45 mm or more are at risk for reoperation, and not until at least after 10.4 years have passed. Neither the valve morphology (p = 0.62) nor concomitant aortic valve replacement (p = 0.86) influenced rate of root dilation. CONCLUSIONS: In nonsyndromic patients, the aortic root is the slowest growing portion of the thoracic aorta. Leaving the native root, as in root-sparing ascending aortic replacement, is a safe approach regarding secondary root intervention for aortic root diameters of 45 mm or less. PMID- 27659604 TI - Automatic classification of registered clinical trials towards the Global Burden of Diseases taxonomy of diseases and injuries. AB - BACKGROUND: Clinical trial registries may allow for producing a global mapping of health research. However, health conditions are not described with standardized taxonomies in registries. Previous work analyzed clinical trial registries to improve the retrieval of relevant clinical trials for patients. However, no previous work has classified clinical trials across diseases using a standardized taxonomy allowing a comparison between global health research and global burden across diseases. We developed a knowledge-based classifier of health conditions studied in registered clinical trials towards categories of diseases and injuries from the Global Burden of Diseases (GBD) 2010 study. The classifier relies on the UMLS(r) knowledge source (Unified Medical Language System(r)) and on heuristic algorithms for parsing data. It maps trial records to a 28-class grouping of the GBD categories by automatically extracting UMLS concepts from text fields and by projecting concepts between medical terminologies. The classifier allows deriving pathways between the clinical trial record and candidate GBD categories using natural language processing and links between knowledge sources, and selects the relevant GBD classification based on rules of prioritization across the pathways found. We compared automatic and manual classifications for an external test set of 2,763 trials. We automatically classified 109,603 interventional trials registered before February 2014 at WHO ICTRP. RESULTS: In the external test set, the classifier identified the exact GBD categories for 78 % of the trials. It had very good performance for most of the 28 categories, especially "Neoplasms" (sensitivity 97.4 %, specificity 97.5 %). The sensitivity was moderate for trials not relevant to any GBD category (53 %) and low for trials of injuries (16 %). For the 109,603 trials registered at WHO ICTRP, the classifier did not assign any GBD category to 20.5 % of trials while the most common GBD categories were "Neoplasms" (22.8 %) and "Diabetes" (8.9 %). CONCLUSIONS: We developed and validated a knowledge-based classifier allowing for automatically identifying the diseases studied in registered trials by using the taxonomy from the GBD 2010 study. This tool is freely available to the research community and can be used for large-scale public health studies. PMID- 27659606 TI - Linking in domain-swapped protein dimers. AB - The presence of knots has been observed in a small fraction of single-domain proteins and related to their thermodynamic and kinetic properties. The exchanging of identical structural elements, typical of domain-swapped proteins, makes such dimers suitable candidates to validate the possibility that mutual entanglement between chains may play a similar role for protein complexes. We suggest that such entanglement is captured by the linking number. This represents, for two closed curves, the number of times that each curve winds around the other. We show that closing the curves is not necessary, as a novel parameter G', termed Gaussian entanglement, is strongly correlated with the linking number. Based on 110 non redundant domain-swapped dimers, our analysis evidences a high fraction of chains with a significant intertwining, that is with |G'| > 1. We report that Nature promotes configurations with negative mutual entanglement and surprisingly, it seems to suppress intertwining in long protein dimers. Supported by numerical simulations of dimer dissociation, our results provide a novel topology-based classification of protein-swapped dimers together with some preliminary evidence of its impact on their physical and biological properties. PMID- 27659605 TI - RNA-binding proteins implicated in neurodegenerative diseases. AB - Gene expression is regulated at many levels, including after generation of the primary RNA transcript from DNA but before translation into protein. Such post translational gene regulation occurs via the action of a multitude of RNA binding proteins and include varied actions from splicing to regulation of association with the translational machinery. Primary evidence that such processes might contribute to disease mechanisms in neurodegenerative disorders comes from the observation of mutations in RNA binding proteins, particularly in diseases in the amyotrophic lateral sclerosis-frontotemporal dementia spectrum and in some forms of ataxia and tremor. The bulk of evidence from recent surveys of the types of RNA species that are affected in these disorders suggests a global deregulation of control rather than a very small number of RNA species, although why some groups of neurons are sensitive to these changes is not well understood. Overall, these data suggest that neurodegeneration can be initiated by mutations in RNA binding proteins and, as a corollary, that neurons are particularly sensitive to loss of control of gene expression at the post-transcriptional level. Such observations have implications not only for understanding the nature of neurodegenerative disorders but also how we might intervene therapeutically in these diseases. WIREs RNA 2017, 8:e1397. doi: 10.1002/wrna.1397 For further resources related to this article, please visit the WIREs website. PMID- 27659607 TI - Hops (Humulus lupulus) Content in Beer Modulates Effects of Beer on the Liver After Acute Ingestion in Female Mice. AB - AIM: Using a binge-drinking mouse model, we aimed to determine whether hops (Humulus lupulus) in beer is involved in the less damaging effects of acute beer consumption on the liver in comparison with ethanol. METHODS: Female C57BL/6 J mice were either fed one iso-alcoholic and iso-caloric bolus dose of ethanol, beer, beer without hops (6 g ethanol/kg body weight) or an iso-caloric bolus of maltodextrin control solution. Markers of steatosis, intestinal barrier function, activation of toll-like receptor 4 signaling cascades, lipid peroxidation and lipogenesis were determined in liver, small intestine and plasma 2 h and 12 h after acute alcohol ingestion. RESULTS: Alcohol-induced hepatic fat accumulation was significantly attenuated in mice fed beer whereas in those fed beer without hops, hepatic fat accumulation was similar to that found in ethanol-fed mice. While markers of intestinal barrier function e.g. portal endotoxin levels and lipogenesis only differed slightly between groups, hepatic concentrations of myeloid differentiation primary response gene 88, inducible nitric oxide synthase (iNOS) and plasminogen-activator inhibitor 1 protein as well as of 4 hydroxynonenal and 3-nitrotyrosine protein adducts were similarly elevated in livers of mice fed ethanol or beer without hops when compared with controls. Induction of these markers was markedly attenuated in mice fed hops-containing beer. CONCLUSION: Taken together, our data suggest that hops in beer markedly attenuated acute alcohol-induced liver steatosis in female mice through mechanisms involving a suppression of iNOS induction in the liver. PMID- 27659609 TI - Strain controlled ferromagnetic-ferrimagnetic transition and vacancy formation energy of defective graphene. AB - Single vacancy (SV)-induced magnetism in graphene has attracted much attention motivated by its potential in achieving new functionalities. However, a much higher vacancy formation energy limits its direct application in electronic devices and the dependency of spin interaction on the strain is unclear. Here, through first-principles density-functional theory calculations, we investigate the possibility of strain engineering towards lowering vacancy formation energy and inducing new magnetic states in defective graphene. It is found that the SV graphene undergoes a phase transition from an initial ferromagnetic state to a ferrimagnetic state under a biaxial tensile strain. At the same time, the biaxial tensile strain significantly lowers the vacancy formation energy. The charge density, density of states and band theory successfully identify the origin and underlying physics of the transition. The predicted magnetic phase transition is attributed to the strain driven spin flipping at the C-atoms nearest to the SV site. The magnetic semiconducting graphene induced by defect and strain engineering suggests an effective way to modulate both spin and electronic degrees of freedom in future spintronic devices. PMID- 27659610 TI - Photosystem II: the water splitting enzyme of photosynthesis and the origin of oxygen in our atmosphere - CORRIGENDUM. PMID- 27659612 TI - Strategic alliances. PMID- 27659613 TI - NHS dentistry: UDA disaster. PMID- 27659611 TI - An 8-Year Retrospective Study of Human Visceral Leishmaniasis. AB - BACKGROUND: Visceral leishmaniasis (VL) is a zooanthroponosis affecting both rural and periurban areas, and can also spread into urban areas. VL has emerged in many countries in the world, presenting new cases in new countries of occurrence. Thus, studies concerning epidemiological aspects in different world regions are very meaningful. METHODS: With this purpose, this study analyzed 89 cases of VL, treated between June 2006 and June 2014 at Eduardo de Menezes Hospital (HEM), a Reference Center of Infectious Diseases situated in Belo Horizonte, in Minas Gerais state, Brazil. RESULTS: According to the results, it was observed that males are mostly infected (84%/n=75) and the most affected age range was 20-49 years old (83%/n=74). The treatment liposomal amphotericin B (33%/n=29) was mostly used. Recurrences were more frequent in patients treated with Glucantime(r) (17%/n=9). No side effects were reported among the 29 patients treated with liposomal amphotericin B. On the other hand, there were 23 cases related to the occurrence of acute renal failure (ARF) and the use of conventional amphotericin B, both when it was administered alone or in combination with other drugs. Additionally, we observed a close relationship between the VL and HIV infection, observing a coinfection rate of 28.1% (n=25). CONCLUSION: From the survey data, it was possible to conclude that the majority of VL patient treated at HEM is male, classified as brown racial group, economically active, and may be drug addicts, chronic alcoholics and/or smokers. They may present some Non-communicable diseases (NCD), such as hypertension, diabetes mellitus, dyslipidemia and/or obesity and, predominantly present a great chance of being a carrier of the Human Immunodeficiency Virus, associated or not with tuberculosis. As symptoms, these patients possibly will present hepatosplenomegaly, fever and pronounced weight loss. PMID- 27659608 TI - The genetics and pathology of mitochondrial disease. AB - Mitochondria are double-membrane-bound organelles that are present in all nucleated eukaryotic cells and are responsible for the production of cellular energy in the form of ATP. Mitochondrial function is under dual genetic control - the 16.6-kb mitochondrial genome, with only 37 genes, and the nuclear genome, which encodes the remaining ~1300 proteins of the mitoproteome. Mitochondrial dysfunction can arise because of defects in either mitochondrial DNA or nuclear mitochondrial genes, and can present in childhood or adulthood in association with vast clinical heterogeneity, with symptoms affecting a single organ or tissue, or multisystem involvement. There is no cure for mitochondrial disease for the vast majority of mitochondrial disease patients, and a genetic diagnosis is therefore crucial for genetic counselling and recurrence risk calculation, and can impact on the clinical management of affected patients. Next-generation sequencing strategies are proving pivotal in the discovery of new disease genes and the diagnosis of clinically affected patients; mutations in >250 genes have now been shown to cause mitochondrial disease, and the biochemical, histochemical, immunocytochemical and neuropathological characterization of these patients has led to improved diagnostic testing strategies and novel diagnostic techniques. This review focuses on the current genetic landscape associated with mitochondrial disease, before focusing on advances in studying associated mitochondrial pathology in two, clinically relevant organs - skeletal muscle and brain. (c) 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID- 27659615 TI - Regulation: Transforming the registers. PMID- 27659614 TI - Pharmaceuticals: MRONJ and prostheses. PMID- 27659616 TI - Mouth cancer: Extending the RULE. PMID- 27659617 TI - Oral health: Mouthwash abuse. PMID- 27659621 TI - Specialist NICE appointment for Professor Kay. PMID- 27659619 TI - Advanced dentistry conference this weekend! PMID- 27659623 TI - Potential quitters turn to e-cigarettes. PMID- 27659626 TI - Report: NHS charges are masking cuts and driving patients to GPs. PMID- 27659627 TI - UCLH staff get tough and muddy for charity. PMID- 27659628 TI - Global oral cancer incidence. PMID- 27659629 TI - Orthodontic allegations raised against registrants by the General Dental Council. AB - An allegation calling a dental professional's Fitness to Practise (FtP) into question is probably one of the most stressful events a General Dental Council (GDC) registrant could face during their career. The practise of dentistry is experiencing unprecedented levels of complaints against registrants with orthodontics traditionally being seen as a low risk area. However, as a recently appointed clinical advisor and expert witness to the GDC, I can testify this may no longer be the case. The last twelve months has seen me provide advice on seven cases associated with orthodontics. This review of frequently occurring allegations in cases being investigated by the GDC should stimulate greater levels of awareness for all members of the dental team and increase the standard of care being provided to our patients. PMID- 27659630 TI - Distal caries of the second molar in the presence of a mandibular third molar - a prevention protocol. AB - Objectives The objectives of the prospective study were to establish the prevalence of distal caries (DC) in the mandibular second molar and to assess the outcomes of these diseased teeth in our population. Further aims were to identify associated risk factors and to design a protocol for prevention.Methods Clinical and radiographic data from 210 consecutive patients were ascertained over a three month period. The sample population included all patients who had been referred to a hospital oral surgery department for a lower wisdom tooth assessment.Results A total of 224 mandibular third molars were included and assessed. The prevalence of caries affecting the distal aspect of the second molar was 38% (n = 85) in this population. In 18% of patients there was evidence of early enamel caries. Fifty-eight percent of caries was managed with restorative treatment but 11% of patients required second molar extraction and 13% of patients required the removal of the second and third molars. The prevalence of distal caries was significantly higher in patients with partially erupted wisdom teeth positioned below the amelocemental junction (P <0.05) of the adjacent second molar and in patients who presented with mesioangular impactions (P <0.001). However there was no difference in dental health when comparing this group to the remaining study population (P = 0.354). The Pearson chi-square test and Pearson correlation coefficient were used to verify the association between the tested variables.Conclusion This study demonstrates that the eruption status, type of angulation and the nature of tooth contact between both molars are useful disease predictors which can be used to indicate the likelihood of a caries process occurring on the distal aspect of the second mandibular molar. If patients' third molar teeth are not removed then consideration needs to be given to prevention and regular monitoring. PMID- 27659632 TI - Missing upper lateral incisor teeth: Space closing versus space opening for bilateral missing upper laterals - aesthetic judgments of laypeople: a web-based survey. AB - Space closure rated more attractive than space opening and prosthetic replacement. PMID- 27659633 TI - Preferences of lay persons and dental professionals regarding the recurring esthetic dental proportion. AB - Dentistry - art or science? PMID- 27659634 TI - Best interest - but for whom?: Clarifying the best interests standard: the elaborative and enumerative strategies in public policy-making. AB - '...decisions being made in murky waters'. PMID- 27659631 TI - Orofacial manifestations of systemic sclerosis. AB - Systemic sclerosis (SSc) is a multisystem disease of unknown aetiology characterised by microangiopathy, dysregulated immune function and tissue remodelling, which commonly involves the oral cavity. Orofacial manifestations of SSc contribute greatly to overall disease burden and yet are regularly overlooked and under-treated. This may reflect a pre-occupation amongst rheumatology clinicians on potentially life-threatening internal organ involvement, but is also a consequence of insufficient engagement between rheumatologists and dental professionals. A high proportion of SSc patients report difficulty accessing a dentist with knowledge of the disease and there is recognition amongst dentists that this could impact negatively on patient care. This review shall describe the clinical features and burden of orofacial manifestations of SSc and the management of such problems. The case is made for greater collaborative working between rheumatologists and dental professionals with an interest in SSc in both the research and clinical setting. PMID- 27659635 TI - Caries experience, the caries burden and associated factors in children in England, Wales and Northern Ireland 2013. AB - Background The 2013 Children's Dental Health Survey is the fifth in a series of national surveys.Aims To describe caries prevalence and severity and factors affecting these, in children in England, Wales and Northern Ireland in 2013.Methodology A representative sample of children (aged 5, 8, 12 and 15 years) in England, Wales and Northern Ireland were invited to participate in dental examinations. Caries was measured at both the dentine ('obvious caries') and dentine plus enamel ('clinical caries') levels and analysis included identifying those with indicators of significant burden of caries and identifying predictive factors.Results In 5-year-olds, 40% had obvious caries experience increasing to 56% when enamel lesions were included. In 15-year-olds, the respective figures were 46% and 63%. Fourteen percent of 5-year-olds and 15% of 15-year-olds had a least one indicator of significant levels of caries and those from deprived backgrounds were more likely to fall into this group.Conclusions Overall, the prevalence of caries in children is continuing to decrease, but the rate is slowing. The level of disease for those with disease is much higher than the average values might suggest and there remain a sizeable minority with a significant burden of caries, associated with deprivation. This complex picture poses significant clinical and public health challenges. PMID- 27659636 TI - An investigation of the clinical experiences of dentists within the national dental foundation training programme in the North West of England. AB - Objective To investigate the clinical experiences of foundation dentists (FDs) in the North West of England.Methods Three research methods were used: a questionnaire completed by FDs at the end of their training; an analysis of the clinical logs of experience recorded in the educational portfolios; and analysis of NHS Business Services Authority (NHSBSA) activity data for the 12 month period of training of FDs.Results A response rate of 100% (N = 50) was achieved for the questionnaire and complete data for 49 of the 50 FDs was available from the NHSBSA and clinical logs in the educational portfolios.Discussion Trainees were satisfied with the clinical experience and believed their workload and patient mix provided a broad experience of clinical conditions, although 40% felt there were gaps in their clinical experience. There were wide ranges in the number of individual clinical procedures performed by FDs with some providing very few endodontic treatments, crowns, bridges, metal dentures and fissure sealants. There was a statistically significant difference (P <0.0005) in self- reporting of procedures recorded in the portfolio log when compared to the NHSBSA data.Conclusion The results from this study suggest that there is satisfaction amongst FDs with FT, but there is wide range in the level of clinical experience amongst FDs with some gaps which need to be addressed. In order to provide a consistent, cost effective approach to the delivery of FT changes are required to ensure minimum levels of clinical procedures are achieved during FT. The information collected in the training portfolio must be robust in order to make valid judgements on progress. PMID- 27659637 TI - A survey of dental practitioners in Wales to evaluate the management of deep carious lesions with vital pulp therapy in permanent teeth. AB - Objective To evaluate the management of deep carious lesions with vital pulp therapy in permanent teeth by dental practitioners within Wales.Design Postal questionnaire.Setting General practitioners (GDS), community (CDS) and hospital based dentists (HDS) in Wales.Methods Community and hospital dental services with a remit for provision of restorative dentistry (CDS = 71; HDS = 46) and general dental practitioners (N = 510) were approached regarding their management of deep carious lesions with vital pulp therapy in permanent teeth. The postal questionnaire took the form of an anonymous survey. Questions covered usage parameters, training issues and reasons for material choice.Results The response rate was 29%. The majority of HDS (89%) used MTA or Biodentine for vital pulp therapy in contrast to GDS (41%) and CDS (32%). The main reasons cited for avoiding the use of MTA or Biodentine included cost, lack of training and difficulty in material handling.Conclusion Usage of MTA or Biodentine for vital pulp therapies is low in the general dental and community dental settings. Cost and lack of training are the main barriers for the uptake of these materials. Postgraduate training may be useful in addressing these barriers. Increasing their adoption would be advantageous as they have been shown to produce a more predictable outcome compared to traditional materials (for example, calcium hydroxide). PMID- 27659638 TI - The development and piloting of the graduate assessment of preparedness for practice (GAPP) questionnaire. AB - Introduction Most new dental graduates in the UK begin their professional career following a year in dental foundation training (DFT). There has been little investigation of how prepared they feel for independent general dental practice across all four domains of the General Dental Council's curriculum 'Preparing for practice'. This paper describes the development of the Graduate Assessment of Preparedness for Practice (GAPP) questionnaire to address this.Methodology The GAPP questionnaire was developed and piloted using a cohort of educational supervisors (ESs) and foundation dentists (FDs). The questionnaire comprised three parts, the first of which collected respondent demographic data. The second was based on Preparing for practice and was used to develop 34 'competence areas' and required a tick-box response on a 7-category Likert Scale. The third comprised free text questions in order to further explore the subject's responses.Results Pilot feedback was positive, the statements were felt to be clear and unambiguous, allowing them sufficient scope to state their position. The pilot study informed small cosmetic changes to the GAPP questionnaire and inclusion of a 'comments' column for respondents to qualify their responses. The pilot results indicated that both FDs and their ESs felt that at ten months of DFT, the FDs were very well prepared for independent general dental practice.Discussion The paper describes the important considerations relating to the reliability and validity of the GAPP questionnaire.Conclusions GAPP appears to be a suitable questionnaire to measure preparedness of new graduates with a degree of reliability and validity. The instrument is designed to be simple to complete and provides a useful analytical instrument for both self-assessment of competence and for wider use within dental education. PMID- 27659639 TI - The undergraduate preparation of dentists: Confidence levels of final year dental students at the School of Dentistry in Cardiff. AB - Objective To investigate the self-reported confidence and preparedness of final year undergraduate students in undertaking a range of clinical procedures.Methods A questionnaire was distributed to final year dental students at Cardiff University, six months prior to graduation. Respondents rated their confidence in undertaking 39 clinical procedures using a 5-point scale (1 = can undertake on own with confidence, 5 = unable to undertake). Students also responded yes/no to experiencing four difficulties and to three statements about general preparedness.Results 71% (N = 51) responded of which 55% (N = 28) were female. Over half reported being 'anxious that the supervisor was not helping enough' (57%) and 'relying heavily on supervisor for help' (53%). Eighty percent 'felt unprepared for the clinical work presented' and gender differences were most notable here (male: 65% N = 33; females: 93% N = 47). Mean confidence scores were calculated for each clinical procedure (1 = lowest; 5 = highest). Confidence was highest in performing 'simple scale' and 'fissure sealant' (mean-score = 5). Lowest scores were reported for 'surgical extractions involving a flap (mean score = 2.28)', 'simple surgical procedures' (mean-score = 2.58) and the 'design/fit/adjustment of orthodontic appliances' (mean-score = 2.88).Conclusions As expected complex procedures that were least practised scored the lowest in overall mean confidence. Gender differences were noted in self-reported confidence for carrying out treatment unsupervised and feeling unprepared for clinical work. PMID- 27659640 TI - Birmingham's new dental school and hospital - A real Peter Pan of dentistry. AB - A look at the history of Birmingham Dental Hospital which, since it was first founded in 1858 as Birmingham Dental Dispensary, has moved six times, the sixth move being to its new Pebble Mill site on 1 April 2016. PMID- 27659662 TI - Is the incidence of type 1 diabetes in children and adolescents stabilising? The first 6 years of a National Register. AB - : The Irish Childhood Diabetes National Register (ICDNR) was established in 2008 to define accurately the incidence and monitor the epidemiology of type 1 diabetes (T1D) in the Irish population. Here, we report data from the first 6 years of the National Register and compare with previous national data. Prospective national incident data regarding T1D in those under 15 years resident in Ireland were collected from 2008 to 2013 and national incidence rates (IRs) calculated. Ascertainment completeness was assessed using capture-recapture methodology. The period identified 1566 new cases of T1D, ascertainment reached 96.8 % in 2013. The standardised incidence rate was 27.5 in 2008 stabilising at 28.7 and 28.8 cases /100,000/year in 2012 and 2013. There was no evidence that the incidence changed significantly in the 6-year period either overall or for each age group and gender. There was evidence of a difference in the incidence of T1D across the age groups with the overall incidence highest in the 10-14 year age category. A strong seasonal association was demonstrated. CONCLUSIONS: This study confirms Ireland as a high-incidence country for type 1 diabetes whilst demonstrating that the previous marked increase in IR from 16.3 cases/100,000/year in 1997 has not continued. Ongoing monitoring through the robust mechanism of the ICDNR is required to clarify whether this is a fluctuation or if the incidence of T1D diabetes has stopped rising in our population. Alternatively, this apparent stabilisation may reflect a shift to a later age at diagnosis. "What is known :" * The incidence of Type 1 diabetes (T1D) is increasing in most populations worldwide although in certain high incidence populations, it may be stabilising * There was a marked increase in T1D in Ireland between 1997 and 2008 * T1D incidence increases with affluence "What is New:" * The high incidence of T1D in Ireland has been confirmed at 28.8 cases/100,000/year in 2013 and has been effectively stable in the period 2008 2013 * Incidence is highest in Irish 10-14 year olds * Changes in incidence possibly reflecting life style and economic climate * Marked seasonality of diagnosis confirmed. PMID- 27659664 TI - Harnessing the Dual Properties of Thiol-Grafted Cellulose Paper for Click Reactions: A Powerful Reducing Agent and Adsorbent for Cu. AB - A new approach exploiting the dual properties of thiol-grafted cellulose paper for promoting copper-catalyzed [3+2]-cycloadditions of organic azides with alkynes and adsorbing residual copper species in solution was developed. The thiol-grafted cellulose paper, used as a paper strip, effects the reduction of CuII to catalytically active CuI and acts as a powerful adsorbent for copper, thereby facilitating the work-up process and leaving the crude mixture almost free of copper residues after a single filtration. PMID- 27659663 TI - Direct cardiac involvement in childhood hemolytic-uremic syndrome: case report and review of the literature. AB - : Overhydration, hypertension, anemia, or dyselectrolytemias sometimes cause cardiovascular impairment in childhood hemolytic-uremic syndrome. Here, we report the case of a 4.5-year-old boy with hemolytic-uremic syndrome and sudden onset, 6 h later, of hemodynamic compromise secondary to a cardiac thrombotic micro angiopathy. The child died. In the literature, we found 18 further cases with cardiac compromise <=25 days after diagnosis. The following causes were found: micro-angiopathy, pericardial blood causing tamponade, and myocarditis. CONCLUSION: We were able to document only 19 cases of childhood hemolytic-uremic syndrome complicated by a direct cardiac compromise. Nonetheless, we speculate that a direct cardiac compromise accounts for many cases of childhood hemolytic uremic syndrome complicated by sudden death during the initial hospitalization. Hence, we propose to always measure troponin in children with hemolytic-uremic syndrome to detect a latent myocardial damage. What is Known: * Overhydration, hypertension, anemia, or dyselectrolytemias sometimes cause cardiovascular impairment in childhood hemolytic-uremic syndrome. What is New: * This study documents 19 cases of childhood hemolytic-uremic syndrome complicated by a direct cardiac compromise <= 25 days after diagnosis. * The Following causes were found: micro-angiopathy, pericardial blood causing tamponade, and myocarditis. PMID- 27659665 TI - Xenotransplantation literature update, July-August 2016. PMID- 27659666 TI - Corrigendum. PMID- 27659668 TI - Genome-wide mapping of nucleosome positions in Saccharomyces cerevisiae in response to different nitrogen conditions. AB - Well-organized chromatin is involved in a number of various transcriptional regulation and gene expression. We used genome-wide mapping of nucleosomes in response to different nitrogen conditions to determine both nucleosome profiles and gene expression events in Saccharomyces cerevisiae. Nitrogen conditions influence general nucleosome profiles and the expression of nitrogen catabolite repression (NCR) sensitive genes. The nucleosome occupancy of TATA-containing genes was higher compared to TATA-less genes. TATA-less genes in high or low nucleosome occupancy, showed a significant change in gene coding regions when shifting cells from glutamine to proline as the sole nitrogen resource. Furthermore, a correlation between the expression of nucleosome occupancy induced NCR sensitive genes or TATA containing genes in NCR sensitive genes, and nucleosome prediction were found when cells were cultured in proline or shifting from glutamine to proline as the sole nitrogen source compared to glutamine. These results also showed that variation of nucleosome occupancy accompany with chromatin-dependent transcription factor could influence the expression of a series of genes involved in the specific regulation of nitrogen utilization. PMID- 27659669 TI - Cleavage of E-Cadherin Contributes to Defective Barrier Function in Neosquamous Epithelium. AB - BACKGROUND: After ablation of Barrett's esophagus (BE), the esophagus heals with neosquamous epithelium (NSE). Despite normal endoscopic appearance, NSE exhibits defective barrier function with similarities to defects noted in the distal esophageal epithelium in patients with gastroesophageal reflux disease (GERD). AIM: To determine whether patients with NSE, unlike patients with healthy esophageal epithelium, have C-terminal fragments (CTFs) of e-cad detectable on tissue biopsy. Secondly, to determine whether patients with NSE have elevated levels of N-terminal fragments (NTFs) of e-cad in the serum. METHODS: Fifteen patients with ablated long-segment BE, who had healing with formation of NSE, were enrolled in this pilot study. Western blots for CTFs and NTFs were performed on biopsies of NSE. Venous blood was obtained to assess levels of NTFs. Endoscopic distal esophageal biopsies from patients without esophageal disease served as tissue controls. Control blood samples were obtained from healthy subjects. RESULTS: Blots of NSE were successful in 14/15 patients, and all 14 (100 %) had a 35-kD CTF of e-cad, while CTFs were absent in healthy control tissues. Despite CTFs in NSE, serum NTFs of e-cad in NSE were similar to controls, p > 0.05. However, unlike healthy controls, blots of NSE also showed NTFs with molecular weights of 70-90 kD. CONCLUSIONS: Cleavage of e-cad, as evidenced by the presence of CTFs and NTFs on biopsy, contributes to defective barrier function in NSE. However, unlike findings reported in GERD patients, serum NTFs are not elevated in NSE patients. This difference may reflect poor absorption with tissue entrapment of NTFs in previously ablated areas with poorly perfused NSE. PMID- 27659670 TI - Response to Feuerstein J et al. "Systematic Analysis and Critical Appraisal of the Quality of the Scientific Evidence and Conflicts of Interest in Practice Guidelines (2005-2013) for Barrett's Esophagus". doi:10.1007/s10620-016-4222-2. PMID- 27659671 TI - Helicobacter pylori Eradication with Proton Pump Inhibitors or Potassium Competitive Acid Blockers: The Effect of Clarithromycin Resistance. AB - BACKGROUND: Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved for Helicobacter pylori eradication therapy in Japan. AIMS: To compare PPI- and P-CAP-containing triple therapy and vonoprazan-based triple therapy. METHODS: Two hundred ninety-five initial subjects received a PPI containing triple therapy; the next 125 subjects received vonoprazan-containing triple therapy. Two sequential groups received 7-day eradication regimens consisting of amoxicillin 750 mg, clarithromycin 200 mg both twice a day with standard dose PPI or vonoprazan (20 mg) each twice daily. H. pylori eradication was confirmed by a 13C-UBT. Clarithromycin susceptibility was evaluated by 23S rRNA PCR. RESULTS: Population cure rates with clarithromycin susceptible strains were 89.6 versus 100 % for PPI and vonoprazan therapies, respectively. Cure rates with resistant strains were 40.2 % with PPI therapy versus 76.1 % with vonoprazan triple therapy. There was no difference in side effects. CONCLUSIONS: Although 7 day P-CAB triple therapy was superior to 7-day PPI triple therapy, neither was highly effective, or can be recommended, in the presence of clarithromycin resistant infections. PMID- 27659672 TI - Age and Prevalence of Esophageal Reflux Disease in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study. AB - BACKGROUND: Only limited epidemiological evidence exists regarding the relationship between age and gastroesophageal reflux disease (GERD) among Japanese patients with type 2 diabetes mellitus. AIM: The purpose of the present study is to investigate this issue among Japanese patients with type 2 diabetes mellitus. METHODS: A multicenter cross-sectional study was conducted in 847 Japanese patients with type 2 diabetes mellitus. Subjects were divided into quartiles according to age: (1) 19 <= age < 56, (2) 56 <= age < 64, (3) 64 <= age < 71, and (4) 71 <= age < 89. GERD was defined as present when a subject had a Carlsson-Dent self-administered questionnaire (QUEST) score >=4. RESULTS: The prevalence of GERD was 31.5 %. Younger age was independently associated with a higher prevalence of GERD: the adjusted odds ratios (95 % confidence intervals) for GERD in relation to age < 56, 56 <= age < 64, 64 <= age < 71, and >=71 were 3.73 (2.16-6.53), 1.98 (1.21-3.27), 1.66 (1.05-2.68), and 1.00 (reference), respectively (P for trend = 0.001). Among 201 patients with PPI or histamine H2 receptor antagonist (H2RA), less than 56 years of age was independently positively associated with GERD: the adjusted OR was 5.68 (95 % CI 1.55-22.18) (P for trend = 0.02). CONCLUSIONS: Younger age may be independently positively associated with GERD among Japanese type 2 diabetes mellitus patients, regardless of the use of PPI or H2RA. PMID- 27659674 TI - Incorporating Clinical Research into a Career in Gastroenterology and Hepatology. PMID- 27659675 TI - Some like it hot: citrus tristeza virus strains react differently to elevated temperature. AB - Viruses often infect plants as a mixed population. The dynamics of viral populations dictate the success of the infection, yet there is little understanding of the factors that influence them. It is known that temperature can affect individual viruses; could it also affect a virus population? In order to study this, we observed citrus tristeza virus (CTV) populations in different hosts under winter and summer conditions (25 versus 36 degrees C). We found that only some CTV strains were affected by a higher summer temperature, which lead to a change in CTV population structure, and that this effect was host dependent. PMID- 27659673 TI - Incidence, Clinical Presentation, and Associated Factors of Microscopic Colitis in Northern France: A Population-Based Study. AB - OBJECTIVE: To date, there are no epidemiological data on microscopic colitis (MC) in France. The aim of this study was to determine the incidence of MC in the Somme department in Northern France, to evaluate clinical characteristics, and to search for risk factors for both collagenous colitis (CC) and lymphocytic colitis (LC). DESIGN: Between January 1, 2005, and December 31, 2007, four pathology units in the Somme department recorded all new cases of MC diagnosed in patients living in the area. Colonic biopsies were reviewed by 4 pathologists together. For each incident case, demographic, clinical, endoscopic, and biological data were collected according to methodology of the EPIMAD registry. RESULTS: One hundred and thirty cases of MC, including 87 CC and 43 LC, were recorded during the three-year study. The mean annual incidence for MC was 7.9/105 inhabitants, 5.3/105 inhabitants for CC, and 2.6/105 inhabitants for LC. Annual standardized incidence of Crohn's disease and ulcerative colitis in the EPIMAD registry during the same period (2005-2007) were 7.4/105 and 4.9/105, respectively. Median age at diagnosis was 63 years for MC, 70 for CC, and 48 for LC. The female-to-male gender ratio was 3.5 for MC, 4.1 for CC, and 2.6 for LC. Median time to diagnosis was 8 weeks. Chronic diarrhea and abdominal pain were, respectively, present in 93 and 47 % of the cases. An autoimmune disease was associated in 28 % of MC cases. At diagnosis, proton pump inhibitor treatment was more often reported in CC than in LC (46 vs 16 %; p = 0.003). Budesonide was effective on diarrhea in 77 % of patients, and thirteen percent of patients became steroid dependent. CONCLUSION: This population-based study shows that the incidence of MC in France is high and similar to Crohn's disease incidence and confirms that this condition is associated with female gender, autoimmune diseases, and medications. PMID- 27659676 TI - HIV-1 sequences isolated from patients promote expression of shorter isoforms of the Gag polyprotein. AB - Human immunodeficiency virus type 1 (HIV-1) unspliced mRNA drives the expression of both Gag and Gag-Pol polyproteins by using both cap- and internal ribosome entry site (IRES)-dependent translation initiation mechanisms. An IRES has been described in the matrix coding region that is involved in the production of shorter isoforms of Gag. However, up to now, this has only been shown with sequences derived from the HIV-1 laboratory strains (NL4.3 and HXB2) and never from clinical HIV-1 isolates. We have isolated ~70 sequences from HIV-1-positive patients that we have sequenced and cloned into an expression vector to monitor their ability to drive translation of Gag p55 and the shorter isoforms both in vitro and ex vivo. The results indicate that (1) the translational efficiency from the AUG-p55 varies significantly among the different isolates; (2) expression initiated at AUG-p40 codon is independent of translation initiation at the AUG-p55 triplet; and (3) all sequences promote expression of shorter Gag isoforms, in particular in Jurkat T cells, in which internal initiation occurs exclusively and directly at the AUG-p40 codon. The composition of the first ~800 nucleotides of the HIV-1 unspliced mRNA modulates the expression initiated both at the AUG-p55 and AUG-p40 codons and may impact viral production and replication. Interestingly, the AUG-p40 codon and its surrounding nucleotide context are conserved amongst clinical isolates and are used as a translation initiation site to produce a shorter Gag isoform. PMID- 27659677 TI - The latency related gene of bovine herpesvirus types 1 and 5 and its modulation of cellular processes. AB - Bovine herpesvirus type 1 (BoHV-1) and bovine herpesvirus type 5 (BoHV-5) are important pathogens of cattle. The diseases they produce are quite different, with BoHV-5 being more neuropathogenic than BoHV-1 which mainly induces respiratory symptoms. The sequencing of the entire BoHV-5 genome has shown that most of the differences between these viruses are found in the immediate early and LR (latency related) genes. The LR gene is the only viral gene abundantly expressed in latently infected neurons, is essential for viral reactivation and seems to have an anti-apoptotic function which can be observed in vivo and in vitro. This gene spans two potential ORFs (1 and 2) which can also be found as a fused version, an ORF-E protein encoded within the promoter region and two miRNAs located within the 5' UTR segment. Most of the essential functions of the LR gene seem to be located within the ORF-2 which has been found to modulate components of cell signaling/cycle pathways. In this review we present a comparative sequence analysis of the LR gene of several BoHV-5 isolates, their differences with the BoHV-1 homologue and the potential impact this may have on its function. The LR gene was found to be highly conserved in all sequenced BoHV-5 strains. ORF 1 shares 60 % homology compared to BoHV-1 whereas the BoHV-5 homologue of ORF-2 is truncated at amino acid 51. Preliminary studies analyzing the emerging transcripts from the BoHV-5 LR gene in infected cells, as well as in stably transfected cells, indicates that their products are, in fact, missing crucial components of the anti-apoptotic function when compared to the BoHV-1 LR gene. In addition these transcripts maintain a region that, similar to what is found in BoHV-1, would produce a miRNA with the potential to recognize a region within the BoHV-5 immediate early gene. All together, these BoHV-5 characteristics suggest that this virus would not possess the same repertoire of latency maintaining functions as BoHV-1. Implications for BoHV-5 neuropathogenic potential are discussed. PMID- 27659678 TI - Infectious bursal disease virus as a replication-incompetent viral vector expressing green fluorescent protein. AB - Infectious bursal disease virus (IBDV) has been established as a replication competent viral vector capable of carrying an epitope at multiple loci in the genome. To enhance the safety and increase the insertion capacity of IBDV as a vector, a replication-incompetent IBDV vector was developed in the present study. The feasibility of replacing one of the viral gene loci, including pvp2, vp3, vp1, or the polyprotein vp243, with the sequence of green fluorescent protein (GFP) was explored. A method combining TCID50 and immunoperoxidase monolayer assay (IPMA) determined the most feasible locus for gene replacement to be pvp2. The genomic segment containing gfp at the pvp2 locus was able to be encapsidated into IBDV particles. Furthermore, the expression of GFP in GFP-IBDV infected cells was confirmed by Western blotting and GFP-IBDV particles showed similar morphology and size to that of wildtype IBDV by electron microscopy. By providing the deleted protein in trans in a packaging cell line (pVP2-DF1), replication incompetent GFP-IBDV particles were successfully plaque-quantified. The gfp sequence from the plaque-forming GFP-IBDV in pVP2-DF1 was confirmed by RT-PCR and sequencing. To our knowledge, GFP-IBDV developed in the present study is the first replication-incompetent IBDV vector which expresses a foreign protein in infected cells without the capability to produce viral progeny. Additionally, such replication-incompetent IBDV vectors could serve as bivalent vaccine vectors for conferring protection against infections with IBDV and other economically important, or zoonotic, avian pathogens. PMID- 27659680 TI - Cardiovascular Disease Outcomes Associated with Three Major Inflammatory Dermatologic Diseases: A Propensity-Matched Case Control Study. AB - INTRODUCTION: Inflammation is an established component of cardiovascular disease (CVD) and an underlying factor of several dermatologic conditions including rosacea, atopic dermatitis, and psoriasis. Identifying potential associations between these dermatologic and cardiovascular diseases can better inform holistic healthcare approaches. The objective of this study was to determine whether rosacea, psoriasis or atopic dermatitis are independent risk factors for CVD 1 year following diagnosis. METHODS: Using a large commercial claims database of 21,801,147 lives, we employed a propensity-matched logistic regression to evaluate the association between diagnoses of rosacea, psoriasis, or atopic dermatitis and a 1-year risk of being diagnosed with cardiovascular disease. Control patients were matched based on health-care utilization, age and overall health status as defined by a modified Deyo-Charlson comorbidity index. RESULTS: The analysis included 2105 rosacea, 622 atopic dermatitis, 1536 psoriasis, and 4263 control patients. Compared to propensity-matched controls, the adjusted odds of cardiovascular disease were not higher in patients with rosacea (odds ratio: 0.894, p = 0.2713), atopic dermatitis (OR 1.032, p = 0.8489), or psoriasis (OR 1.087, p = 0.4210). In univariate analysis, the unadjusted odds of cardiovascular disease was higher in patients with psoriasis (OR 1.223, p = 0.0347). CONCLUSIONS: Limitations of this study include the short follow-up period and inclusion of only commercially insured patients limit the generalizability of these findings. In this large study of patients with rosacea, atopic dermatitis, and psoriasis, we did not detect an increased 1-year risk of cardiovascular disease after adjusting for confounders. PMID- 27659679 TI - An imbalance between specialized pro-resolving lipid mediators and pro inflammatory leukotrienes promotes instability of atherosclerotic plaques. AB - Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro inflammatory leukotriene B4 (LTB4), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr-/- mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB4 ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability. PMID- 27659681 TI - Variation in the strength of reproductive interference from an alien congener to a native species in Taraxacum. AB - Reproductive interference (RI) may be a contributing factor to the displacement of native species by an alien congener, and RI strength has been shown theoretically to affect distributional relationships between species. Thus, variations in RI strength from alien to native species result in different consequences of invasions and efforts to conserve native species, but the variations have seldom been examined empirically. We therefore investigated RI strength variations from the alien species Taraxacum officinale and its hybrids to eight populations of native dandelions, four T. japonicum populations and two populations each of two subspecies of T. platycarpum. We examined the association between alien relative abundance and native seed set in field surveys, and we also performed hand-pollination experiments to investigate directly the sensitivity of native flowers to alien pollen. We found that the effect of alien relative abundance on native seed set of even the same native species could differ greatly in different regions, and that the sensitivity of native flowers to alien pollen was also dependent on region. Our results, together with those of previous studies, show that RI from the alien to the native species is strong in regions where the alien species outnumbers the native species and marginal where it does not; this result suggests that alien RI can critically affect distributional relationships between native and alien species. Our study highlights the importance of performing additional empirical investigations of RI strength variation and of giving due attention to alien RI in efforts to conserve regional native biodiversity. PMID- 27659682 TI - Transmission of survival signals through Delta-like 1 on activated CD4+ T cells. AB - Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+ T cells from Dll1-/- and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1-/- mice compared with control cells. Dll1-/- mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1-/- mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch signaling important for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses. PMID- 27659683 TI - A Step Toward a Better Understanding of the Relationship Between Victimization and Emotional Distress: Indirect Effect of Adult Attachment and Interaction With Household Dysfunction. AB - A history of victimization has been linked to the latter development of emotional distress. However, not all victims develop emotional distress in response to victimization, emphasizing the need to identify mediators that can guide intervention, as well as moderators to more targeted preventive actions. Within a developmental psychology framework, we aimed to test two models: (a) the role of adult attachment as a mediator in the relationship between victimization and emotional distress, and (b) the role of household dysfunctions as moderators in the relationship between victimization and emotional distress, in psychiatric patients. Participants were 120 adult psychiatric patients, between ages 20 and 79 years ( M = -47.22, SD = 13.102) that responded to questions assessing household dysfunction in the family of origin, victimization, and adult attachment. Results revealed that adult attachment was a significant mediator in the association between victimization and emotional distress. Parental mental disorder and total household adversity were significant moderators for that same association. These results provide important clues for intervention. The focus on promoting secure adult relationships may contribute not only to the psychosocial adjustment of psychiatric patients but also to a healthier family functioning. Reducing the household dysfunction may provide a protective environment for the development of children, promoting a positive psychosocial adjustment, also preventing the intergenerational transmission of violence, insecure attachment, and emotional distress. PMID- 27659684 TI - African American Perspectives and Experiences of Domestic Violence in a Rural Community. AB - Relatively few studies have explored domestic violence from a multiplicity of African American perspectives, experiences, and socio-demographic backgrounds within rural African American communities. Community-based participatory action research methods were used to explore domestic violence perceptions of African Americans with heterogeneous backgrounds and experiences of violence. Ten focus groups were held throughout the community with 52 diverse women ( n = 33) and men ( n = 19) living in the northwest region of Arkansas. Demographic data were collected from 47 women ( n = 28) and men ( n = 19) participating in focus groups regarding their perceptions and experiences of domestic violence, media messages, help-seeking behaviors, and services. Data were analyzed using grounded theory methods. Three major themes emerged, including (a) a heightened awareness of race, gender, and class differences; (b) imbalanced and mixed messages from media; and (c) multi-systemic dynamics influencing abusive behavior and relationships. Results indicate that study participants' perspectives and experiences with domestic violence reflect a complex interrelated gamut of societal, community, familial, and individual dynamics. Participant recommendations related to interpersonal dynamics, media messages, and societal influences are reported with implications for practice, policy, and future research. PMID- 27659685 TI - Predictors of Perceived Need for and Actual Action Taking Among Women in Violent Relationships. AB - Decision-making of women in violent relationships is poorly understood. The study seeks to identify predictors of need-for-action and actions taken by women in violent relationships. The participants were 143 women who experienced violence in previous month from 6 primary care clinics. The methods involved multiple times series using daily assessments of household environment, marital relationship, concerns, violence, and need-for-action collected via telephone interactive voice response for 8 weeks. Outcomes include daily need-for-action and reports of actions taken. Same-day correlates and prior-day associations using vector autoregressions were sought, combined across subjects using meta analytic techniques. Need for help depended on stalking, concern for child safety, forgiveness, and low perceived control; actually seeking help depended on sense of control with same-day stress and need for help. Need for legal action depended on concern for child safety and finances with desire to keep family together; actually taking legal action, correlated only with prior-day stalking and concerns about child safety but less about effects of violence on child. Need to leave depended on his violence, with concern about its effect on child, her forgiveness, and a low desire to keep family together, while actually leaving was primed by a day of his drinking, and triggered by same-day stress and need to leave, but lower levels of her drinking or his seeking forgiveness. Once gone, prior-day stalking and his alcohol use correlated with returning to the relationship. Taking action depends upon few prior- and same-day factors unique to each action. PMID- 27659686 TI - Decrypting ENCODEd epigenetic marks of human tRN-A-RS genes in normal, stem and cancer cell lines. AB - Screening large-scale ENCODE data of 625 cytoplasmic transfer RNA (tRNAs) and 37 aminoacyl tRNA synthetase (AARSs) human genes, we deconstruct the array of relations between 10 histone marks affecting 15 chromatin states; their tissue specificity and variations and interchange amongst normal, cancerous and stem cells. The histone marks of RNA Pol II transcribed AARS genes share, but also contrast with that on RNA Pol III transcribed tRNA genes. tRNAs with identical/similar sequences may be in significantly varying states even within the same cell line; the chromatin scaffold, where the tRNA gene resides, is the key determinant. Hepatocellular carcinoma cell line has dominant H3K27me3, and singular clustering of other marks. Leukaemic cell line has hyperactive genes. The quiescence of the stem cells is encoded in the markers. Leaving aside the important exceptions in stem cells and elsewhere, tRNAs with cove scores above 50 have active markers and precise sets of transcription factors, and are usually well conserved compared to the low-scoring ones. Pseudo tRNAs are in heterochromatin/repressed state with anomalous exceptions in cancer cells. We motivate that Epigenetic-Phishing hacks the translation apparatus through the chromatin states governed by the histone marks of tRNA and AARS genes, and speculate on their therapeutic implications in cancer and on stem cells. PMID- 27659687 TI - A Pilot Clinical Study in Characterization of Malignant Renal-cell Carcinoma Subtype with Contrast-enhanced Ultrasound. AB - Malignant renal cell carcinoma (RCC) is a diverse set of diseases, which are independently difficult to characterize using conventional MRI and CT protocols due to low temporal resolution to study perfusion characteristics. Because different disease subtypes have different prognoses and involve varying treatment regimens, the ability to determine RCC subtype non-invasively is a clinical need. Contrast-enhanced ultrasound (CEUS) has been assessed as a tool to characterize kidney lesions based on qualitative and quantitative assessment of perfusion patterns, and we hypothesize that this technique might help differentiate disease subtypes. Twelve patients with RCC confirmed pathologically were imaged using contrast-enhanced ultrasound. Time intensity curves were generated and analyzed quantitatively using 10 characteristic metrics. Results showed that peak intensity ( p = 0.001) and time-to-80% on wash-out ( p = 0.004) provided significant differences between clear cell, papillary, and chromophobe RCC subtypes. These results suggest that CEUS may be a feasible test for characterizing RCC subtypes. PMID- 27659688 TI - Expression of Cucumber mosaic virus suppressor 2b alters FWA methylation and its siRNA accumulation in Arabidopsis thaliana. AB - The Cucumber mosaic virus (CMV) suppressor 2b co-localizes with AGO4 in cytoplasmic and nuclear fractions of Arabidopsis thaliana Biochemical fractionation of A. thaliana cellular extracts revealed that 2b and AGO4 coexist in multiple size exclusions. 2b transgenic A. thaliana exhibited an enhanced accumulation of 24nt siRNAs from flowering wageningen (FWA) and other heterochromatic loci. These plants also exhibited hypo-methylation of an endogenous- as well as transgene-FWA promoter at non-CG sites. In corroboration, both transgenic 2b and CMV infection affected the regulation of transposons which mimics the ago4 phenotype. In conclusion, 2b perturbs plant defense by interfering with AGO4-regulated transcriptional gene silencing. PMID- 27659689 TI - Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR) and type 2 diabetes (T2D), for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4) corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis), which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD. PMID- 27659690 TI - Directional cell movements downstream of Gbx2 and Otx2 control the assembly of sensory placodes. AB - Cranial placodes contribute to sensory structures including the inner ear, the lens and olfactory epithelium and the neurons of the cranial sensory ganglia. At neurula stages, placode precursors are interspersed in the ectoderm surrounding the anterior neural plate before segregating into distinct placodes by as yet unknown mechanisms. Here, we perform live imaging to follow placode progenitors as they aggregate to form the lens and otic placodes. We find that while placode progenitors move with the same speed as their non-placodal neighbours, they exhibit increased persistence and directionality and these properties are required to assemble morphological placodes. Furthermore, we demonstrate that these factors are components of the transcriptional networks that coordinate placode cell behaviour including their directional movements. Together with previous work, our results support a dual role for Otx and Gbx transcription factors in both the early patterning of the neural plate border and the later segregation of its derivatives into distinct placodes. PMID- 27659691 TI - In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium. AB - Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches. PMID- 27659692 TI - A New Questionnaire (QRFPC25) Regarding the Religiosity and Spirituality in People with Life-Threatening Disease: Reliability and Validity in a Population of Cancer Patients Undergoing Radiotherapy. AB - The development of a questionnaire (QRFPC25) assessing the religiosity of cancer patients. The method used for the questionnaire comprises seven multi-item and three single-item scales formed from a 25-question module. The questionnaire was completed on-site and a week after antineoplastic therapy. The final sample included 156 patients. The main topics of the QRFPC25 are the following: worship, relationship with the divine, spiritual discussion, hope, participation in holly communion, faith, life after death, love, bioethics and global quality of life (QoL). The average time of both times taken to complete the questionnaire was approximately 10 min. All multi-item scales met the minimal standards of reliability (Cronbach's alpha coefficient >=.70) before or after treatment. Test retest reliability in terms of the intraclass correlation coefficient was also satisfactory (p < 0.01). Validity was assured by inter-item correlations and correlations with the European Organisation for Research and Treatment of Cancer's Core Quality of Life Questionnaire (QLQ-C30, version 3.0), along with factor analysis which showed eight factors incorporated in the model. The QRFPC25 is a reliable and valid gauge for the assessment of religiosity in cancer patients undergoing radiotherapy. PMID- 27659693 TI - Modulation of yeast telomerase activity by Cdc13 and Est1 in vitro. AB - Telomerase is the enzyme involved in extending telomeric DNA. Control of telomerase activity by modulating its access to chromosome ends is one of the most important fundamental mechanisms. This study established an in vitro yeast telomerase reconstitution system that resembles telomere replication in vivo. In this system, a tailed-duplex DNA formed by telomeric DNA was employed to mimic the structure of telomeres. The core catalytic components of telomerase Est2/Tlc1 RNA were used as the telomeric DNA extension machinery. Using the reconstituted systems, this study found that binding of Cdc13 to telomeric DNA inhibited the access of telomerase to its substrate. The result was further confirmed by a single-molecule approach using the tethered-particle motion (TPM)-based telomerase assay. The findings also showed that the inhibitory effect can be relieved by telomerase-associated protein Est1, consistent with the role of Cdc13 and Est1 in regulating telomere extension in vivo. Significantly, this study found that the DNA binding property of Cdc13 was altered by Est1, providing the first mechanistic evidence of Est1 regulating the access of telomerase to its substrate. Thus, the roles of Cdc13 and Est1 in modulating telomerase activity were clearly defined using the in vitro reconstituted system. PMID- 27659695 TI - Development of an Indicator Displacement Based Detection of Malaria Targeting HRP II as Biomarker for Application in Point-of-Care Settings. AB - A novel label free spectrophotometric detection of malarial biomarker HRP-II following an indicator displacement assay has been developed. The assay is based on competitive displacement of murexide dye from its complex with Ni2+ by HRP-II present in serum samples. The binding constant (Kd) discerned for the dye and HRP II to Ni2+ were 1.4 * 10-6 M-1 and 6.8 * 10-9 M-1, respectively. The progress of the reaction could be monitored from the change of color from orange (~lambda482 nm) to pink (~lambda515 nm) with the concomitant increase in HRP-II concentration in the mixture. A linear response (R2 = 0.995) curve was generated by plotting the ratio of absorbance (lambda515 nm/lambda482 nm) against the HRP-II concentrations. The method offers to detect HRP-II as low as 1 pM without any interference from some common salts and the major protein, HSA, present in the blood serum. The detection method was reproduced in a microfluidic paper based analytical device (MUPAD), fabricated by printing hydrophobic alkyl ketene dimer on a chromatographic paper to create hydrophilic microchannels, test zone, and sample application zone. The device offers to use a maximum sample volume of 20 +/- 0.06 MUL and detects HRP-II within 5 min with LOD of 30 +/- 9.6 nM in a dynamic range of 10 to 100 nM. The method has thus immense potential to develop as rapid, selective, simple, portable, and inexpensive malarial diagnostic device for point-of-care and low resource setting applications. PMID- 27659696 TI - Newly Proposed Prognostic Grade Group System for Prostate Cancer: Genesis, Utility and its Implications in Clinical Practice. AB - We know about the Gleason pattern and Gleason score which are of paramount importance in tailoring the treatment of a prostate cancer. However, there are certain deficiencies in this current scoring system. To simplify the treatment options and have a better idea about the prognosis, a new grade group system has been proposed by ISUP/WHO in 2015. This has been validated in the clinical practice. This commentary takes you through its genesis, utility and its implications on the clinical practice. PMID- 27659694 TI - Expression of immunoproteasome genes is regulated by cell-intrinsic and extrinsic factors in human cancers. AB - Based on transcriptomic analyses of thousands of samples from The Cancer Genome Atlas, we report that expression of constitutive proteasome (CP) genes (PSMB5, PSMB6, PSMB7) and immunoproteasome (IP) genes (PSMB8, PSMB9, PSMB10) is increased in most cancer types. In breast cancer, expression of IP genes was determined by the abundance of tumor infiltrating lymphocytes and high expression of IP genes was associated with longer survival. In contrast, IP upregulation in acute myeloid leukemia (AML) was a cell-intrinsic feature that was not associated with longer survival. Expression of IP genes in AML was IFN-independent, correlated with the methylation status of IP genes, and was particularly high in AML with an M5 phenotype and/or MLL rearrangement. Notably, PSMB8 inhibition led to accumulation of polyubiquitinated proteins and cell death in IPhigh but not IPlow AML cells. Co-clustering analysis revealed that genes correlated with IP subunits in non-M5 AMLs were primarily implicated in immune processes. However, in M5 AML, IP genes were primarily co-regulated with genes involved in cell metabolism and proliferation, mitochondrial activity and stress responses. We conclude that M5 AML cells can upregulate IP genes in a cell-intrinsic manner in order to resist cell stress. PMID- 27659698 TI - Lorcaserin treatment allows for decreased number needed to treat for weight and glycemic parameters in week 12 responders with >=5% weight loss. AB - OBJECTIVES: Lorcaserin is a serotonin 2C receptor agonist approved for chronic weight management. This analysis explores the number of patients needed to be treated (NNT) with lorcaserin for one more patient to achieve weight loss and glycemic goals. METHODS: This is a post hoc analysis of three Phase 3 studies in adults with and without type 2 diabetes mellitus (T2DM) treated with lorcaserin 10 mg BID or placebo. NNT is reported for patients achieving >=5% or >=10% weight loss, achievement of either HbA1c <5.7% or FPG <100 mg/dL in patients with prediabetes, and reduction of HbA1c to <7% in patients with T2DM at Week 52. RESULTS: In the modified intention-to-treat (MITT) population, NNTs for >=5% and >=10% weight loss were 3.6 and 6.2 (without T2DM) and 4.3 and 7.5 (with T2DM); in Week 12 responders (>=5% weight loss at Week 12), NNTs were 1.7 and 2.6 (without T2DM) and 1.9 and 3.2 (with T2DM). In patients with prediabetes, NNTs to achieve HbA1c <5.7% were 9.9 (MITT) and 5.2 (Week 12 responders). In patients with T2DM, NNTs to achieve HbA1c <7% were 4.2 (MITT) and 2.3 (Week 12 responders). CONCLUSION: In addition to weight management, lorcaserin improved glycemic control in patients with prediabetes and facilitated targeted HbA1c reduction in patients with T2DM, especially for those who achieved >=5% weight loss by Week 12. Assessment of treatment response at Week 12 is a valuable tool to achieve efficient use of healthcare resources. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT00395135, NCT00603291, and NCT00603902. PMID- 27659697 TI - Minimally Invasive Sacrocolpopexy: How to Avoid Short- and Long-Term Complications. AB - Sacrocolpopexy remains the "gold standard" procedure for management of posthysterectomy vaginal vault prolapse with improved anatomic outcomes compared to native tissue vaginal repair. Despite absence of clinical data, sacrocolpopexy is increasingly being offered to women as a primary treatment intervention for uterine prolapse. While reoperation rates remain low, recurrent prolapse and vaginal mesh exposure appear to increase over time. The potential morbidity associated with sacrocolpopexy is higher than for native tissue vaginal repair with complications including sacral hemorrhage, discitis, small bowel obstruction, port site herniation, and mesh erosion. Complications are more common during the learning curve of minimally invasive sacrocolpopexy. Appropriate case selection is paramount to balancing the potential for prolapse recurrence with the risk of surgical complications. Use of ultra-lightweight polypropylene mesh and vaginal mesh attachment with delayed absorbable suture may reduce the risks of vaginal mesh exposure. PMID- 27659699 TI - Opioid-receptor antagonism increases pain and decreases pleasure in obese and non obese individuals. AB - RATIONALE: Endogenous opioids inhibit nociceptive processing and promote the experience of pleasure. It has been proposed that pain and pleasure lie at opposite ends of an affective spectrum, but the relationship between pain and pleasure and the role of opioids in mediating this relationship has not been tested. OBJECTIVES: Here, we used obese individuals as a model of a dysfunctional opioid system to assess the role of the endogenous opioid peptide, beta endorphin, on pain and pleasure sensitivity. METHODS: Obese (10M/10F) and age- and gender-matched non-obese (10M/10F) controls were included in the study. Pain sensitivity using threshold, tolerance, and subjective rating assessments and perceived sweet pleasantness using sucrose solutions were assessed in two testing sessions with placebo or the opioid antagonist, naltrexone (0.7 mg/kg body weight). Beta-endorphin levels were assessed in both sessions. RESULTS AND CONCLUSIONS: Despite having higher levels of baseline beta-endorphin and altered beta-endorphin-reactivity to naltrexone, obese individuals reported a similar increase in pain and decrease in pleasantness following naltrexone compared to non-obese individuals. Beta-endorphin levels did not correlate with pain or pleasantness in either group, but naltrexone-induced changes in pain and pleasantness were mildly correlated. Moreover, naltrexone-induced changes in pain were related to depression scores, while naltrexone-induced changes in sweet pleasantness were related to anxiety scores, indicating that pain and pleasantness are related, but influenced by different processes. PMID- 27659700 TI - Aortic root dimensions are predominantly determined by genetic factors: a classical twin study. AB - OBJECTIVES: Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. METHODS: In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 +/- 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). RESULTS: Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CONCLUSION: CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. KEY POINTS: * Aortic root dimensions are determined by genetic and environmental effects. * Transthoracic echocardiography (TTE) demonstrated moderate to no genetic effects on aortic root dimensions. * Computed tomography angiography might provide more accurate heritability estimates compared to TTE. * Three-dimensional imaging techniques are needed to reliably quantify aortic root dimensions. PMID- 27659703 TI - Correction to "Deoxygenation Increases Photoluminescence Lifetime of Protein Responsive Organic Probes with Triplet-Singlet Resonant Energy Transfer". PMID- 27659701 TI - Extralobar pulmonary sequestration in neonates: The natural course and predictive factors associated with spontaneous regression. AB - PURPOSE: To describe the natural course of extralobar pulmonary sequestration (EPS) and identify factors associated with spontaneous regression of EPS. MATERIALS AND METHODS: We retrospectively searched for patients diagnosed with EPS on initial contrast CT scan within 1 month after birth and had a follow-up CT scan without treatment. Spontaneous regression of EPS was assessed by percentage decrease in volume (PDV) and percentage decrease in sum of the diameter of systemic feeding arteries (PDD) by comparing initial and follow-up CT scans. Clinical and CT features were analysed to determine factors associated with PDV and PDD rates. RESULTS: Fifty-one neonates were included. The cumulative proportions of patients reaching PDV > 50 % and PDD > 50 % were 93.0 % and 73.3 % at 4 years, respectively. Tissue attenuation was significantly associated with PDV rate (B = -21.78, P < .001). The tissue attenuation (B = -22.62, P = .001) and diameter of the largest systemic feeding arteries (B = -48.31, P = .011) were significant factors associated with PDD rate. CONCLUSION: The volume and diameter of systemic feeding arteries of EPS spontaneously decreased within 4 years without treatment. EPSs showing a low tissue attenuation and small diameter of the largest systemic feeding arteries on initial contrast-enhanced CT scans were likely to regress spontaneously. KEY POINTS: * Extralobar pulmonary sequestration (EPS) could show spontaneous regression. * Initial CT features may predict spontaneous regression of EPS. * The tissue attenuation and diameter of systemic feeding artery are important factors. PMID- 27659704 TI - Asymptomatic rheumatoid meningitis revealed by magnetic resonance imaging, followed by systemic rheumatic vasculitis: A case report and a review of the literature. AB - We report the case of a 66-year-old man with seropositive rheumatoid arthritis who developed neurologically asymptomatic rheumatoid meningitis (RM) revealed by MRI. RM worsened and chest CT showed pericardial effusion, pleural effusion, and bilateral consolidation, and his serum C3 level was decreased. We diagnosed systemic rheumatic vasculitis based on these findings. After a review of more than 20 previously reported cases of RM, this is the first case of RM without central nerve system symptoms. PMID- 27659705 TI - The role of extracellular vesicles in neurodegenerative diseases. AB - Extracellular vesicles, including exosomes, are small membranous vesicles released from many biotypes, contributing to the disease progression and spreading. These extracellular vesicles provide an important mode of cell-to-cell communication by delivering proteins, lipids and RNA to target cells. Exosomes are found associated with neurodegenerative diseases, which are characterised by progressive degeneration of neurons and often associated with misfolded protein. The common diseases include Parkinson's disease (PD), Alzheimer's diseases (AD), amyotrophic lateral sclerosis (ALS), and the prion diseases. Of all neurodegenerative diseases, prion diseases are classified as the distinctive group owing to its transmissible and infectious nature of misfolded prion protein. The infectious prion particles have been demonstrated to be present in exosomes to spread prion infectivity within cells. Similarly, misfolded proteins involved in other neurodegenerative diseases such as Amyloid-beta and tau in AD, alpha-synuclein in PD, and superoxide dismutase 1 in ALS have been demonstrated to exploit exosomes for induced spreading of misfolded proteins in a prion-like mechanism. Furthermore, RNA molecules can be taken up by the recipient cells as cargo in exosomes. These RNAs can module the expression of the target genes by repressing or inhibiting protein translation. Here we review the role of exosomes in prion diseases and other common neurodegenerative diseases, and discuss the potential of these vesicles for disease pathogenesis. PMID- 27659702 TI - MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation. AB - OBJECTIVES: To assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence. METHODS: Qualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months. RESULTS: Post-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases (p < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast enhancement, with a hyperintense rim on ceMRI. Ablation zone volume increase was noted on both modalities in the first 6 weeks, followed by a decrease (p < 0.05). In the patients developing tumour recurrence (5/25), a focal DWI-b800 hyperintense spot at 6 weeks predated unequivocal recurrence on CT. CONCLUSION: The most remarkable signal alterations after pancreatic IRE were shown by DWI-b800 and ceMRI. These early imaging characteristics may be useful to establish technical success and predict treatment outcome. KEY POINTS: * This study describes imaging characteristics after irreversible electroporation (IRE) for pancreatic adenocarcinoma. * Familiarity with typical post-IRE imaging characteristics helps to interpret ablation zones. * Post-IRE, no central and variable rim enhancement are visible on contrast-enhanced imaging. * DWI-b800 may prove useful to predict early tumour recurrence. * Post-IRE examinations reveal an initial volume increase followed by a decrease. PMID- 27659706 TI - Characterization of urocortin as an anti-apoptotic protein in experimental ischemia-reperfusion model of the rat testis. AB - The objective of this study was to investigate the role of urocortin in testicular apoptosis using an experimental ischemia-reperfusion rat model. To evaluate the change in urocortin expression and apoptotic status in the testes following ischemia-reperfusion, the left testes of rats were rotated clockwise by 720 degrees for 1 h, and were then harvested at 0, 1, 3, 6 and 24 h after detorsion (n = 5 in each group). A time-dependent increase in the expression levels of urocortin was noted until 6 h after reperfusion, but the expression of urocortin was markedly decreased 24 h after reperfusion. However, a TUNEL assay showed that the proportion of germ cells undergoing apoptosis significantly increased 24 h after reperfusion compared with that of 6 h after reperfusion. To clarify whether or not urocortin directly regulates the testicular apoptosis induced by ischemia-reperfusion, either astressin, an antagonist of urocortin, or normal saline was injected into the rat testes 15 min before detorsion, followed by the testicular torsion. The testes were then removed 3 h after detorsion (n = 5 in each group). The testicular injection of astressin significantly increased the proportion of TUNEL-positive germ cells, and significantly decreased expression of Bcl-2 and Bcl-xL. In addition, the level of phosphorylated ERK 1/2, but not that of phosphorylated Akt, was significantly reduced by the intratesticular administration of astressin. These findings suggest that urocortin may play a cytoprotective role in the germ cells in response to ischemia-reperfusion injury through the activation of major anti-apoptotic proteins, as well as by the mitogen-activated protein kinase signaling pathway activation. PMID- 27659707 TI - Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency. AB - Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site. However, energy function calculations using statistical potentials indicate that the mutation causes a decrease in ASM stability. Therefore, we investigated the functional effect of the p.Ala359Asp mutation in ASM expression, secretion, localization and activity in human fibroblasts. We found a 3.8% residual ASM activity compared to the wild-type enzyme, without changes in the other parameters evaluated. These results support the hypothesis that the p.Ala359Asp mutation causes structural alterations in the hydrophobic environment where ASM is located, decreasing its enzymatic activity. A similar effect was observed in other previously described NPDB mutations located outside the active site of the enzyme. This work shows the first full size ASM mutant model describe at date, providing a complete analysis of the structural and functional effects of the p.Ala359Asp mutation over the stability and activity of the enzyme. PMID- 27659708 TI - Neighbors' death is required for surviving human adenocarcinoma PC-9 cells in an early stage of gefitinib treatment. AB - Acquired drug resistance is a major problem in chemotherapy, and understanding of the mechanism, by which naive cells defend themselves from drugs when the cells exposed to the drugs for the first time, may provide a solution of the problem. Gefitinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and used as an anticancer drug; however, gefitinib treatment may sometimes lead cancer cells gradually into a gefitinib-tolerance. Here we describe that human adenocarcinoma PC-9 cells even under the presence of gefitinib were able to survive by activating another signaling pathway involving fibroblast growth factor receptor (FGFR) and its signaling molecule, FGF2; and further suggest that the FGF2 for initiating the pathway might be supplied from neighboring cells which were killed by gefitinib, i.e., the survival might be founded on neighbors' sacrifice in an early stage of gefitinib treatment. Our findings suggested that whether cells had a chance to encounter to survival factors such as FGF2 soon after gefitinib treatment might be an important crossroads for the cells for survival and for gaining a gefitinib tolerance. PMID- 27659709 TI - Palmitoylation of the carboxyl-terminal tail of dopamine D4 receptor is required for surface expression, endocytosis, and signaling. AB - The amino acid sequences and signaling pathways of D2-like dopamine receptors (D2R, D3R, and D4R) are highly conserved. D4R has been suggested to be associated with novelty seeking, and binds with high affinity to an atypical antipsychotic drug with fewer motor function-related side effects than typical neuroleptics. A study comparing D2R and D3R reported that palmitoylation is important for the proper functioning of D3R. Although D4R is a member of the D2-like receptor family, its palmitoylation status and the functional significance of any such posttranslational modification are unknown. In this study, it was found that D4 4, an alternatively spliced form of D4R, was palmitoylated on Cys467, the terminal amino acid residue of the receptor. When palmitoylation of D4R was inhibited, by either mutation of the consensus site or by treatment with the palmitoylation inhibitor 2-bromopalmitate (2BP), D4R cell surface expression, signaling, and endocytosis were all impaired. Exchanging the carboxyl-terminal tails of D2R and D4R resulted in a switching of the palmitoylation phenotype, as well as concomitant changes in functionality, such as receptor surface expression, endocytosis, and signaling. Despite the high degree of homology in the carboxyl-terminal tails of D2-like receptors, palmitoylation occurs exclusively in the D3R and D4R family members, with the D4R tail being sufficient to endow D2R with palmitoylation-associated functionality. Thus, this study provides new insights into a consensus sequence for palmitoylation, as well as possible strategies for the regulation of D4R, which has implications for the treatment of various neurological and psychiatric disorders. PMID- 27659711 TI - [Pulmonary manifestations in collagen vascular diseases]. AB - CLINICAL/METHODICAL ISSUE: Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. STANDARD RADIOLOGICAL METHODS: The standard radiological procedure for the work up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. PERFORMANCE: The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. ACHIEVEMENTS: Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. PRACTICAL RECOMMENDATIONS: At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management. PMID- 27659712 TI - Clinical and molecular characterization of a novel INS mutation identified in patients with MODY phenotype. AB - Correct diagnosis of Maturity-Onset Diabetes of the Young (MODY) is based on genetic tests requiring an appropriate subject selection by clinicians. Mutations in the insulin (INS) gene rarely occur in patients with MODY. This study is aimed at determining the genetic background and clinical phenotype in patients with suspected MODY. 34 patients with suspected MODY, negative for mutations in the GCK, HNF1alpha, HNF4alpha, HNF1beta and PDX1 genes, were screened by next generation sequencing (NGS). A heterozygous INS mutation was identified in 4 members of the same family. First genetic tests performed identified two heterozygous silent nucleotide substitutions in MODY3/HNF1alpha gene. An ineffective attempt to suspend insulin therapy, administering repaglinide and sulphonylureas, was made. DNA was re-sequenced by NGS investigating a set of 102 genes. Genes implicated in the pathway of pancreatic beta-cells, candidate genes for type 2 diabetes mellitus and genes causative of diabetes in mice were selected. A novel heterozygous variant in human preproinsulin INS gene (c.125T > C) was found in the affected family members. The new INS mutation broadens the spectrum of possible INS phenotypes. Screening for INS mutations is warranted not only in neonatal diabetes but also in MODYx patients and in selected patients with type 1 diabetes mellitus negative for autoantibodies. Subjects with complex diseases without a specific phenotype should be studied by NGS because Sanger sequencing is ineffective and time consuming in detecting rare variants. PMID- 27659713 TI - Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects. AB - We report a 20 year follow up on a Caucasian female, now 26 years of age, with Prader-Willi syndrome (PWS) harboring an atypical 15q11-q13 submicroscopic deletion of 100-200 kb in size first detected in 1996 involving the imprinting center, SNRPN gene and surrounding region. PWS is a rare complex disorder caused by the loss of paternally expressed genes in the 15q11-q13 region. With high resolution chromosomal microarray and methylation - specific MLPA analysis, we updated the genetic findings on our patient and found a 209,819bp deletion including the SNURF-SNRPN gene complex which includes the imprinting center and the SNORD116 region. We compared with four other similarly reported individuals in the literature with atypical submicroscopic deletions within this region but without imprinting center involvement to better characterize the specific genetic lesions causing PWS clinical findings. Clinically, our patient met the diagnostic criteria of PWS including infantile hypotonia, a poor suck with feeding difficulties, global developmental delays and later food foraging, childhood obesity, small hands and skin picking. Small atypical deletions of comparable sizes were seen in the 15q11-q13 region in all five cases and similar behavioral/physical characteristics were found despite an imprinting defect in our patient. These results further support an overlapping critical deletion region involving the non-coding snoRNA SNORD116 in common in the five individuals playing a key role in contributing to the PWS phenotype. PMID- 27659710 TI - Emerging pathways driving early synaptic pathology in Alzheimer's disease. AB - The current state of the AD research field is highly dynamic is some respects, while seemingly stagnant in others. Regarding the former, our current lack of understanding of initiating disease mechanisms, the absence of effective treatment options, and the looming escalation of AD patients is energizing new research directions including a much-needed re-focusing on early pathogenic mechanisms, validating novel targets, and investigating relevant biomarkers, among other exciting new efforts to curb disease progression and foremost, preserve memory function. With regard to the latter, the recent disappointing series of failed Phase III clinical trials targeting Abeta and APP processing, in concert with poor association between brain Abeta levels and cognitive function, have led many to call for a re-evaluation of the primacy of the amyloid cascade hypothesis. In this review, we integrate new insights into one of the earliest described signaling abnormalities in AD pathogenesis, namely intracellular Ca2+ signaling disruptions, and focus on its role in driving synaptic deficits - which is the feature that does correlate with AD-associated memory loss. Excess Ca2+release from intracellular stores such as the endoplasmic reticulum (ER) has been well-described in cellular and animal models of AD, as well as human patients, and here we expand upon recent developments in ER-localized release channels such as the IP3R and RyR, and the recent emphasis on RyR2. Consistent with ER Ca2+ mishandling in AD are recent findings implicating aspects of SOCE, such as STIM2 function, and TRPC3 and TRPC6 levels. Other Ca2+-regulated organelles important in signaling and protein handling are brought into the discussion, with new perspectives on lysosomal regulation. These early signaling abnormalities are discussed in the context of synaptic pathophysiology and disruptions in synaptic plasticity with a particular emphasis on short-term plasticity deficits. Overall, we aim to update and expand the list of early neuronal signaling abnormalities implicated in AD pathogenesis, identify specific channels and organelles involved, and link these to proximal synaptic impairments driving the memory loss in AD. This is all within the broader goal of identifying novel therapeutic targets to preserve cognitive function in AD. PMID- 27659715 TI - Florida child care center directors' intention to implement oral health promotion practices in licensed child care centers. AB - BACKGROUND: To determine the factors associated with child care center directors' (CCCDs) intention to implement oral health promotion practices (OHPPs) in licensed childcare centers (CCCs) within the next year, and their self-perceived barriers in successfully implementing those practices. METHODS: For this cross sectional study, a pretested 45-item online survey was sent to 5142 CCCDs assessing pediatric oral health knowledge, attitudes towards oral health, intention to implement OHPPs, and self-perceived barriers to implementing OHPPs. An adjusted logistic regression model determined the factors associated with CCCDs intention to implement OHPPs within the next year. RESULTS: Participants were 877 CCCDs, with mean age of 48.5 +/- 10.5 years, of whom 96 % were women, and 74 % were whites (Response rate = 19.4 %). The majority (67 %) of respondents reported that they intended to implement OHPPs in their center within a year. Insufficient funding, lack of enough training in oral health, and limited time to promote oral health were the most frequently cited barriers to implementing OHPPs. CCCDs of non-White race (p = 0.02), with a college degree or above (p = 0.05), and with positive attitudes (p < 0.0001), were more likely to report that they will implement OHPPs within the next year compared to their counterparts. CONCLUSIONS: CCCDs reported fewer barriers to implementing OHPPs within the next year, indicating that CCCs can be a suitable setting to promote oral health. CCCDs race, educational status and attitudes towards oral health strongly predicted their intention to implement OHPPs. Though this study assessed the intention of CCCDs to implement OHPPs in CCCs, it did not access the actual implementation of OHPPs by them. Therefore future research could longitudinally assess predictors for true implementation of OHPPs. In addition, researchers should adopt a more comprehensive, multi-level approach to assess the actual dental health needs of children attending these centers, along with parental, staff and center level characteristics, and other relevant factors related to implementing OHPPs. PMID- 27659714 TI - Endothelial cell-derived pentraxin 3 limits the vasoreparative therapeutic potential of circulating angiogenic cells. AB - AIMS: Circulating angiogenic cells (CACs) promote revascularization of ischaemic tissues although their underlying mechanism of action and the consequences of delivering varying number of these cells for therapy remain unknown. This study investigates molecular mechanisms underpinning CAC modulation of blood vessel formation. METHODS AND RESULTS: CACs at low (2 * 105 cells/mL) and mid (2 * 106 cells/mL) cellular densities significantly enhanced endothelial cell tube formation in vitro, while high density (HD) CACs (2 * 107 cells/mL) significantly inhibited this angiogenic process. In vivo, Matrigel-based angiogenesis assays confirmed mid-density CACs as pro-angiogenic and HD CACs as anti-angiogenic. Secretome characterization of CAC-EC conditioned media identified pentraxin 3 (PTX3) as only present in the HD CAC-EC co-culture. Recombinant PTX3 inhibited endothelial tube formation in vitro and in vivo. Importantly, our data revealed that the anti-angiogenic effect observed in HD CAC-EC co-cultures was significantly abrogated when PTX3 bioactivity was blocked using neutralizing antibodies or PTX3 siRNA in endothelial cells. We show evidence for an endothelial source of PTX3, triggered by exposure to HD CACs. In addition, we confirmed that PTX3 inhibits fibroblast growth factor (FGF) 2-mediated angiogenesis, and that the PTX3 N-terminus, containing the FGF-binding site, is responsible for such anti-angiogenic effects. CONCLUSION: Endothelium, when exposed to HD CACs, releases PTX3 which markedly impairs the vascular regenerative response in an autocrine manner. Therefore, CAC density and accompanying release of angiocrine PTX3 are critical considerations when using these cells as a cell therapy for ischaemic disease. PMID- 27659716 TI - Disease-modifying activity of ruxolitinib in a patient with JAK2-negative CMML-2. PMID- 27659717 TI - Antibiotic resistance patterns and genetic relatedness of Enterococcus faecalis and Enterococcus faecium isolated from military working dogs in Korea. AB - Enterococcus spp. are normally present in the gastrointestinal tracts of animals and humans, but can cause opportunistic infections that can be transmitted to other animals or humans with integrated antibiotic resistance. To investigate if this is a potential risk in military working dogs (MWDs), we analyzed antibiotic resistance patterns and genetic relatedness of Enterococcus spp. isolated from fecal samples of MWDs of four different age groups. Isolation rates of Enterococcus spp., Enterococcus (E.) faecalis, and E. faecium, were 87.7% (57/65), 59.6% (34/57), and 56.1% (32/57), respectively, as determined by bacterial culture and multiplex PCR. The isolation rate of E. faecalis gradually decreased with age (puppy, 100%; adolescent, 91.7%; adult, 36.4%; and senior, 14.3%). Rates of resistance to the antibiotics ciprofloxacin, gentamicin, streptomycin, sulfamethoxazole/trimethoprim, imipenem, and kanamycin among Enterococcus spp. increased in adolescents and adults and decreased in senior dogs, with some isolates having three different antibiotic resistance patterns. There were indistinguishable pulsed-field gel electrophoresis patterns among the age groups. The results suggest that Enterococcus is horizontally transferred, regardless of age. As such, periodic surveillance studies should be undertaken to monitor changes in antibiotic resistance, which may necessitate modification of antibiotic regimens to manage antibiotic resistance transmission. PMID- 27659718 TI - Comparative risk of self-harm hospitalization amongst depressive disorder patients using different antidepressants: a population-based cohort study in Taiwan. AB - BACKGROUND: The aim of the study was to evaluate the comparative risk of self harm associated with the use of different antidepressants. METHOD: A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950-E958 and E980-E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment. RESULTS: There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5 7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40 6.45], milnacipran (aHR = 2.34, 95% CI 1.24-4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06-1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30-0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). CONCLUSIONS: The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors. PMID- 27659719 TI - Methodological issues associated with clinical trials in neuropathic pain. PMID- 27659722 TI - Investment in general practice rises slightly after years of cuts. PMID- 27659720 TI - Establishment and functions of DNA methylation in the germline. AB - Epigenetic modifications established during gametogenesis regulate transcription and other nuclear processes in gametes, but also have influences in the zygote, embryo and postnatal life. This is best understood for DNA methylation which, established at discrete regions of the oocyte and sperm genomes, governs genomic imprinting. In this review, we describe how imprinting has informed our understanding of de novo DNA methylation mechanisms, highlight how recent genome wide profiling studies have provided unprecedented insights into establishment of the sperm and oocyte methylomes and consider the fate and function of gametic methylation and other epigenetic modifications after fertilization. PMID- 27659723 TI - Phylogenomics solves a long-standing evolutionary puzzle in the ciliate world: The subclass Peritrichia is monophyletic. AB - The phylum Ciliophora is one of the most broadly studied protozoan lineages. The era of molecular investigation has brought forth a major ongoing debate: is the subclass Peritrichia Stein, 1859 monophyletic? Numerous analyses mostly using the small subunit (SSU) rRNA gene have failed to recover the Mobilida and Sessilida, the two peritrich orders, as sister clades. Here we have sequenced five peritrich species - three sessilids and two mobilids. We constructed a supermatrix of 158 genes and 44,696 characters for 24 ciliate species, and as outgroup taxa, nine species from the Apicomplexa and four from the Dinophyceae. Our analyses using both maximum likelihood and Bayesian methods recover a monophyletic class Oligohymenophorea and two robust clades within it. The first clade is a monophyletic Peritrichia with the orders Sessilida and Mobilida maximally supported as sister clades. The second oligohymenophorean clade includes species of the subclasses Scuticociliatia and Hymenostomatia, which are sister clades. Our analyses resolve a long-standing debate in ciliate molecular phylogenetics and provide support for the classical view that the morphological features of the two peritrich orders Mobilida and Sessilida arose by descent from the same common ancestor and are not the result of convergence. PMID- 27659721 TI - Classification and Regression Tree (CART) analysis to predict influenza in primary care patients. AB - BACKGROUND: The use of neuraminidase-inhibiting anti-viral medication to treat influenza is relatively infrequent. Rapid, cost-effective methods for diagnosing influenza are needed to enable appropriate prescribing. Multi-viral respiratory panels using reverse transcription polymerase chain reaction (PCR) assays to diagnose influenza are accurate but expensive and more time-consuming than low sensitivity rapid influenza tests. Influenza clinical decision algorithms are both rapid and inexpensive, but most are based on regression analyses that do not account for higher order interactions. This study used classification and regression trees (CART) modeling to estimate probabilities of influenza. METHODS: Eligible enrollees >= 5 years old (n = 4,173) who presented at ambulatory centers for treatment of acute respiratory illness (<=7 days) with cough or fever in 2011 2012, provided nasal and pharyngeal swabs for PCR testing for influenza, information on demographics, symptoms, personal characteristics and self-reported influenza vaccination status. RESULTS: Antiviral medication was prescribed for just 15 % of those with PCR-confirmed influenza. An algorithm that included fever, cough, and fatigue had sensitivity of 84 %, specificity of 48 %, positive predictive value (PPV) of 23 % and negative predictive value (NPV) of 94 % for the development sample. CONCLUSIONS: The CART algorithm has good sensitivity and high NPV, but low PPV for identifying influenza among outpatients >=5 years. Thus, it is good at identifying a group who do not need testing or antivirals and had fair to good predictive performance for influenza. Further testing of the algorithm in other influenza seasons would help to optimize decisions for lab testing or treatment. PMID- 27659724 TI - Waking the undead: Implications of a soft explosive model for the timing of placental mammal diversification. AB - The explosive, long fuse, and short fuse models represent competing hypotheses for the timing of placental mammal diversification. Support for the explosive model, which posits both interordinal and intraordinal diversification after the KPg mass extinction, derives from morphological cladistic studies that place Cretaceous eutherians outside of crown Placentalia. By contrast, most molecular studies favor the long fuse model wherein interordinal cladogenesis occurred in the Cretaceous followed by intraordinal cladogenesis after the KPg boundary. Phillips (2016) proposed a soft explosive model that allows for the emergence of a few lineages (Xenarthra, Afrotheria, Euarchontoglires, Laurasiatheria) in the Cretaceous, but otherwise agrees with the explosive model in positing the majority of interordinal diversification after the KPg mass extinction. Phillips (2016) argues that rate transference errors associated with large body size and long lifespan have inflated previous estimates of interordinal divergence times, and further suggests that most interordinal divergences are positioned after the KPg boundary when rate transference errors are avoided through the elimination of calibrations in large-bodied and/or long lifespan clades. Here, we show that rate transference errors can also occur in the opposite direction and drag forward estimated divergence dates when calibrations in large-bodied/long lifespan clades are omitted. This dragging forward effect results in the occurrence of more than half a billion years of 'zombie lineages' on Phillips' preferred timetree. By contrast with ghost lineages, which are a logical byproduct of an incomplete fossil record, zombie lineages occur when estimated divergence dates are younger than the minimum age of the oldest crown fossils. We also present the results of new timetree analyses that address the rate transference problem highlighted by Phillips (2016) by deleting taxa that exceed thresholds for body size and lifespan. These analyses recover all interordinal divergence times in the Cretaceous and are consistent with the long fuse model of placental diversification. Finally, we outline potential problems with morphological cladistic analyses of higher-level relationships among placental mammals that may account for the perceived discrepancies between molecular and paleontological estimates of placental divergence times. PMID- 27659725 TI - A hybrid robust fault tolerant control based on adaptive joint unscented Kalman filter. AB - In this paper, a new hybrid robust fault tolerant control scheme is proposed. A robust Hinfinity control law is used in non-faulty situation, while a Non Singular Terminal Sliding Mode (NTSM) controller is activated as soon as an actuator fault is detected. Since a linear robust controller is designed, the system is first linearized through the feedback linearization method. To switch from one controller to the other, a fuzzy based switching system is used. An Adaptive Joint Unscented Kalman Filter (AJUKF) is used for fault detection and diagnosis. The proposed method is based on the simultaneous estimation of the system states and parameters. In order to show the efficiency of the proposed scheme, a simulated 3-DOF robotic manipulator is used. PMID- 27659726 TI - Omnidirectional autonomous entry guidance based on 3-D analytical glide formulas. AB - An autonomous entry guidance law is developed based on 3-D analytical glide formulas, where the downrange formula is used to plan the longitudinal reference profile in order to meet the downrange and final energy requirements, and the crossrange formula is used to regulate the bank reversals in order to eliminate the crossrange error. As the analytical glide formulas ignore the effects of the Earth's rotation, a series of strategies is proposed for compensating these effects, which provides the guidance with the capability of steering the hypersonic glide vehicle with high Lift to Drag ratio (L/D) to any place of the world accurately. The compensation strategies can be summarized into two parts: (1) the reference profiles are properly adjusted by roughly evaluating the effects of the Earth's rotation on the aerodynamic profiles over the whole flight, which can compensate most of the effects; (2) the current effects are accurately evaluated and then the guidance commands are slightly modulated for compensating the remaining effects. Due to careful design, the strategies will not result in drastic changes in the Angle of Attack (AOA) and can keep the bank angle almost constant during most of flight. PMID- 27659727 TI - Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. AB - : A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). METHODS: A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. RECOMMENDATIONS: The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast. PMID- 27659728 TI - Prevalence of PTSD and other mental disorders in UK service personnel by time since end of deployment: a meta-analysis. AB - BACKGROUND: US studies have shown an increase of posttraumatic stress disorder (PTSD) and depression, but not alcohol misuse related to time of assessment since returning from deployment. We assessed if similar trends occur in the UK Armed Forces. METHODS: We selected UK studies based on our data base of King's Centre for Military Health Research publications from 2006 until January 2016 with at least one of the following measures: PTSD checklist-civilian version (PCL-C), the General Health Questionnaire (GHQ-12) and the Alcohol Use Disorders Identification Test (AUDIT). The studies included personnel assessed for these outcomes after their most recent deployment. A search in Medline, Psycho-Info and Embase confirmed that no relevant publication was missed. RESULTS: Twenty one thousand, seven hundred and forty-six deployed personnel from nine studies contributed to the meta-analyses by time since end of deployment in the PTSD analysis. The number of studies for period of time varied from two to four studies. The trend by time-category of questionnaire completion since returning from deployment were for PTSD beta = 0.0021 (95 % CI -0.00046 to 0.0049, p = 0.12), for psychological distress beta = 0.0123 (95 % CI 0.005 to 0.019, p = 0.002) and for alcohol misuse beta = 0.0013 (-0.0079 to 0.0105, p = 0.77). CONCLUSIONS: There was no evidence that the prevalence of PTSD and alcohol misuse changed according to time since the end of deployment over a three-year period, but there was evidence for an association with increasing psychological distress. PMID- 27659729 TI - Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines. AB - Reactive oxygen species (ROS) in the brain are involved in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. This study was designed to determine whether chronic infusion of EGCG into the hypothalamic paraventricular nucleus (PVN) attenuates ROS and sympathetic activity and delays the progression of hypertension by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and decreasing nuclear factor-kappa B (NF-kappaB) activity, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) rats and SHR received bilateral PVN infusion of EGCG (20MUg/h) or vehicle via osmotic minipumps for 4 weeks. SHR showed higher mean arterial pressure, plasma proinflammatory cytokines and circulating norepinephrine (NE) levels compared with WKY rats. SHR also had higher PVN levels of the subunit of NAD(P)H oxidase (gp91phox), ROS, tyrosine hydroxylase, and PICs; increased NF-kappaB activity; and lower PVN levels of interleukin-10 (IL-10) and 67kDa isoform of glutamate decarboxylase (GAD67) than WKY rats. PVN infusion of EGCG attenuated all these changes in SHR. These findings suggest that SHR have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN. Chronic inhibition of ROS in the PVN restores the balance of neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive response and sympathetic activity. PMID- 27659730 TI - Differential sensitivities of bone marrow, spleen and thymus to genotoxicity induced by environmentally relevant concentrations of arsenite. AB - It is known in humans and mouse models, that drinking water exposures to arsenite (As+3) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As+3, and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As+3via drinking water for 30d. Oxidation State Specific Hydride Generation- Cryotrapping Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA+3) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA+3 levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As+3 and MMA+3 revealed that bone marrow cells are most sensitive to As+3 treatment, and MMA+3 is more genotoxic than As+3. These results suggest that the differential sensitivities of the three immune organs to As+3 exposure are due to the different intracellular arsenic species and concentrations, and that MMA+3 may play a critical role in immunotoxicity. PMID- 27659731 TI - Parabens inhibit fatty acid amide hydrolase: A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation. AB - Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1) selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids. PMID- 27659732 TI - Cisplatin-induced toxicity decreases the mouse vestibulo-ocular reflex. AB - Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0.5, 1.0 and 2.5Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16mg/kg, but not 8mg/kg, decreased the VOR gain at 2.5Hz compared with the vehicle control. Following 16mg/kg cisplatin treatment, the animals showed no change in the optokinetic nystagmus response, suggesting that no major changes in visual or oculomotor functions had occurred. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment. PMID- 27659733 TI - HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa. AB - BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART. METHODS: A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to Stanford HIVdb v7.0.1. RESULTS: A total of 788 sequences were available for analysis. Most patients failed a tenofovir-based NRTI backbone (74.4%) in combination with efavirenz (82.1%) after median treatment duration of 36 months. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. Only one-third of patients retained full susceptibility to second-generation NNRTIs such as etravirine (36.5%) and rilpivirine (27.3%). After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. Cross-resistance to NRTIs was often observed, but did not seem to affect the predicted activity of zidovudine as 82.9% of patients remained fully susceptible to this drug. CONCLUSIONS: The introduction of tenofovir-based first line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. However, most patients failing tenofovir based regimens remained fully susceptible to zidovudine. Based on these data, there is currently no need to change either the recommended first- or second-line ART regimens in South Africa. PMID- 27659734 TI - ST147 NDM-1-producing Klebsiella pneumoniae spread in two Tunisian hospitals. PMID- 27659735 TI - Role of cephalosporins in the era of Clostridium difficile infection. AB - The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011-12 to 2012-13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes. PMID- 27659736 TI - The hazards of bad sleep-Sleep duration and quality as predictors of adolescent alcohol and cannabis use. AB - BACKGROUND: Although an association between adolescent sleep and substance use is supported by the literature, few studies have characterized the longitudinal relationship between early adolescent sleep and subsequent substance use. The current study examined the prospective association between the duration and quality of sleep at age 11 and alcohol and cannabis use throughout adolescence. METHODS: The present study, drawn from a cohort of 310 boys taking part in a longitudinal study in Western Pennsylvania, includes 186 boys whose mothers completed the Child Sleep Questionnaire; sleep duration and quality at age 11 were calculated based on these reports. At ages 20 and 22, participants were interviewed regarding lifetime alcohol and cannabis use. Cox proportional hazard analysis was used to determine the association between sleep and substance use. RESULTS: After accounting for race, socioeconomic status, neighborhood danger, active distraction, internalizing problems, and externalizing problems, both the duration and quality of sleep at age 11 were associated with multiple earlier substance use outcomes. Specifically, less sleep was associated with earlier use, intoxication, and repeated use of both alcohol and cannabis. Lower sleep quality was associated with earlier alcohol use, intoxication, and repeated use. Additionally, lower sleep quality was associated with earlier cannabis intoxication and repeated use, but not first use. CONCLUSIONS: Both sleep duration and sleep quality in early adolescence may have implications for the development of alcohol and cannabis use throughout adolescence. Further studies to understand the mechanisms linking sleep and substance use are warranted. PMID- 27659737 TI - Magnetic resonance imaging phantoms for quality-control of myocardial T1 and ECV mapping: specific formulation, long-term stability and variation with heart rate and temperature. AB - BACKGROUND: Magnetic resonance imaging (MRI) phantoms are routinely used for quality assurance in MRI centres; however their long term stability for verification of myocardial T1/ extracellular volume fraction (ECV) mapping has never been investigated. METHODS: Nickel-chloride agarose gel phantoms were formulated in a reproducible laboratory procedure to mimic blood and myocardial T1 and T2 values, native and late after Gadolinium administration as used in T1/ECV mapping. The phantoms were imaged weekly with an 11 heart beat MOLLI sequence for T1 and long TR spin-echo sequences for T2, in a carefully controlled reproducible manner for 12 months. RESULTS: There were only small relative changes seen in all the native and post gadolinium T1 values (up to 9.0 % maximal relative change in T1 values) or phantom ECV (up to 8.3 % maximal relative change of ECV, up to 2.2 % maximal absolute change in ECV) during this period. All native and post gadolinium T2 values remained stable over time with <2 % change. Temperature sensitivity testing showed MOLLI T1 values in the long T1 phantoms increasing by 23.9 ms per degree increase and short T1 phantoms increasing by 0.3 ms per degree increase. There was a small absolute increase in ECV of 0.069 % (~0.22 % relative increase in ECV) per degree increase. Variation in heart rate testing showed a 0.13 % absolute increase in ECV (~0.45 % relative increase in ECV) per 10 heart rate increase. CONCLUSIONS: These are the first phantoms reported in the literature modeling T1 and T2 values for blood and myocardium specifically for the T1mapping/ECV mapping application, with stability tested rigorously over a 12 month period. This work has significant implications for the utility of such phantoms in improving the accuracy of serial scans for myocardial tissue characterisation by T1 mapping methods and in multicentre work. PMID- 27659738 TI - SCN8A Epileptic Encephalopathy: Detection of Fetal Seizures Guides Multidisciplinary Approach to Diagnosis and Treatment. AB - BACKGROUND: SCN8A mutations are rare and cause a phenotypically heterogeneous early onset epilepsy known as early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558). There are currently no clear genotype-phenotype correlations to help guide patient counseling and management. PATIENT DESCRIPTION: We describe a patient with EIEE13 (de novo heterozygous pathogenic mutation in SCN8A - p.Ile240Val (ATT>GTT)) who presented prenatally with maternally reported intermittent, rhythmic movements that, when observed on ultrasound, were concerning for fetal seizures. Ultrasound also revealed abnormal developmental states. With maternal administration of levetiracetam, the rhythmic fetal movements stopped. After birth, the patient developed treatment-refractory multi-focal epilepsy confirmed by electroencephalogram. Neuroimaging revealed restricted diffusion in the superior cerebellar peduncles, a finding not reported previously in EIEE13. CONCLUSION: This is the first report of EIEE13 associated with clinical prenatal-onset seizures. Ultrasonography can be useful for identifying fetal seizures, which may be treatable in utero. Ideally, the clinical approach to fetal seizures should involve a multidisciplinary team spanning the pre- and postnatal course to expedite early diagnosis and optimize management, as illustrated by this patient. PMID- 27659739 TI - Rapid infectious disease identification by next-generation DNA sequencing. AB - Currently, there is a critical need to rapidly identify infectious organisms in clinical samples. Next-Generation Sequencing (NGS) could surmount the deficiencies of culture-based methods; however, there are no standardized, automated programs to process NGS data. To address this deficiency, we developed the Rapid Infectious Disease Identification (RIDITM) system. The system requires minimal guidance, which reduces operator errors. The system is compatible with the three major NGS platforms. It automatically interfaces with the sequencing system, detects their data format, configures the analysis type, applies appropriate quality control, and analyzes the results. Sequence information is characterized using both the NCBI database and RIDITM specific databases. RIDITM was designed to identify high probability sequence matches and more divergent matches that could represent different or novel species. We challenged the system using defined American Type Culture Collection (ATCC) reference standards of 27 species, both individually and in varying combinations. The system was able to rapidly detect known organisms in <12h with multi-sample throughput. The system accurately identifies 99.5% of the DNA sequence reads at the genus-level and 75.3% at the species-level in reference standards. It has a limit of detection of 146cells/ml in simulated clinical samples, and is also able to identify the components of polymicrobial samples with 16.9% discrepancy at the genus-level and 31.2% at the species-level. Thus, the system's effectiveness may exceed current methods, especially in situations where culture methods could produce false negatives or where rapid results would influence patient outcomes. PMID- 27659740 TI - Changes of CFTR functional measurements and clinical improvements in cystic fibrosis patients with non p.Gly551Asp gating mutations treated with ivacaftor. AB - Ivacaftor, a CFTR potentiator, has been found to improve CFTR function and clinical outcomes in patients with cystic fibrosis (CF) gating mutations. We investigated the effects of ivacaftor on CFTR functional measurement in CF patients carrying gating mutations other than p.Gly551Asp. Two siblings aged 13 and 12 carrying the p.Ser549Asn mutation, two sisters (45 and 43years old) compound heterozygotes for p.Asp1152His and p.Gly1244Glu, a 37year old man homozygous for the p.Gly1244Glu mutation, and a 7year old girl with p.Arg352Gln and p.Gly1244Glu mutations commenced treatment with ivacaftor. NPD was performed in all the patients and approached normal for four patients who had also clinical improvement (p.Ser549Asn compound heterozygotes, and p.Asp1152His/p.Gly1244Glu siblings). Beta-adrenergic sweat chloride secretion performed in thep.Asp1152His/p.Gly1244Glu patients improved significantly. The p.Gly1244Glu mutation homozygous patient, who had undergone an ileal resection with ileostomy and enterocutaneous fistula, did not respond clinically to ivacaftor and did not modify his sweat test. These results highlight the importance of different CFTR activity measurements to explore CFTR modulator efficacy. PMID- 27659741 TI - A multidisciplinary telehealth program in patients with combined chronic obstructive pulmonary disease and chronic heart failure: study protocol for a randomized controlled trial. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist, significantly reducing patients' quality of life and increasing morbidity and mortality. For either single disease, a multidisciplinary disease-management approach supported by telecommunication technologies offers the best outcome in terms of prolonged survival and reduced hospital readmissions. However, no data exist in patients with combined COPD/CHF. We planned a randomized controlled trial to investigate the feasibility and efficacy of an integrated, home-based, medical/nursing intervention plus a rehabilitation program versus conventional care in patients with coexisting COPD/CHF. The purpose of the paper is to describe the rationale and design of the trial. METHODS/DESIGNS: Patients, after inpatient rehabilitation, were randomly assigned to the intervention or control group, followed for 4 months at home, then assessed at 4 and 6 months. The intervention group followed a telesurveillance (telephone contacts by nurse and remote monitoring of cardiorespiratory parameters) and home-based rehabilitation program (at least three sessions/week of mini-ergometer exercises, callisthenic exercises and twice weekly pedometer-driven walking, plus telephone contacts by a physiotherapist). Telephone follow-up served to verify compliance to therapy, maintain exercise motivation, educate for early recognition of signs/symptoms, and verify the skills acquired. At baseline and 4 and 6 months, the 6-min Walk Test, dyspnea and fatigue at rest, oxygenation (PaO2/FiO2), physical activity profile (PASE questionnaire), and QoL (Minnesota and CAT questionnaires) were assessed. During the study, serious clinical events (hospitalizations or deaths) were recorded. DISCUSSION: Currently, no studies have assessed the impact of a telehealth program in patients with combined COPD and CHF. Our study will show whether this approach is effective in the management of such complex, frail patients who are at very high risk of exacerbations. TRIAL REGISTRATION: Network per la prevenzione e la sanita pubblica, CCM, Ministero della Salute "Modelli innovativi di gestione integrata telegestita ospedale-territorio del malato cronico a fenotipo complesso: studio di implementazione, validazione e impatto," registered on 14 January 2014. ClinicalTrials.gov Identifier: NCT02269618 , registered on 17 October 2014. PMID- 27659742 TI - [Type I interferonopathies. Literature review]. AB - Thanks to the tremendous progress of genetics, a new field of inherited inflammatory disorders related to an overproduction of interferon has recently emerged. The so-called type I interferonopathies represent an heterogeneous group of Mendelian diseases presenting with various features starting in childhood, although the diagnosis can also be made later in life. Several clinical and biological characteristics are shared across these patients such as a positive interferon (IFN) signature and neurological and cutaneous involvement, some of which display organ specificity. Treatment is challenging, but IFN-targeting therapies represent a promising option in these severe diseases. PMID- 27659743 TI - [Mevalonate kinase deficiency in 2016]. AB - Mevalonate kinase deficiency is a rare, autosomal recessive, auto-inflammatory disease. This results from mutations in the gene MVK coding for the enzyme mevalonate kinase. This enzyme is involved in cholesterol and isoprenoids synthesis. Depending partially of the residual activity of the mevalonate kinase, the clinical spectrum realizes a continuum which extends from the mild phenotype of the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to a lethal form of mevalonic aciduria. The HIDS is characterized by recurrent episodes of fever with an intense inflammatory syndrome, accompanied with lymphadenopathy, abdominal pain, diarrhea, arthralgia, hepatomegaly, splenomegaly and skin rash. The first attack more frequently takes place in the first year of life, even during the neonatal period, where it can be confused with a maternofetal infection. There is furthermore in mevalonate aciduria a psychomotor retardation, a failure to thrive, a cerebellar ataxia, a dysmorphic syndrome and a reduction of the visual acuity. The diagnosis is based on the mevalonic aciduria during febrile attack. Genetics confirm the diagnosis in more than 80 % of the cases. The dosage of IgD, low sensitive and specific, has no interest. There is no reference treatment. The less severe forms can be treated by non-steroidal anti inflammatory drugs or steroids during febrile attacks. The most severe patients can be treated by biotherapy: antagonists of IL-1, TNF-alpha and IL-6. PMID- 27659744 TI - [Tumor-induced osteomalacia caused by a late-revealing phosphaturic mesenchymal tumor]. AB - INTRODUCTION: Osteomalacia is associated with diffuse pain and multiple fractures and therefore, diagnosis and treatment of this condition are necessary. Clinicians should be aware of an uncommon mechanism of osteomalacia where hypophosphataemia is secondary to renal phosphaturia because of the production by a mesenchymal phosphaturic tumor of FGF-23. This tumor should be localized and removed to cure this tumor-induced osteomalacia. OBSERVATION: A 70-year-old female patient was admitted to explore diffuse pain caused by multiple fractures secondary to osteomalacia. Despite vitamin D supplementation, she remained profoundly hypophosphoremic with major renal phosphaturia. A tumor-induced mechanism was suspected because of high level of FGF-23. It took more than three years of investigation to spot the causal phosphaturic mesenchymal tumor despite annual repetition of indium-labelled scintigraphy and PET-scan. The resection of the tumor, located between two phalanges of the right foot, cured the patient with sustained normal rate of serum level of phosphorus after two years. CONCLUSION: Tumor-induced osteomalacia is a diagnostic challenge because the localization of the tumor may be a long process. Patients should be monitored clinically and imaging studies repeated until a diagnosis is made and the causal tumor removed. PMID- 27659745 TI - [Nocardiosis: A retrospective case series of 19 patients]. AB - INTRODUCTION: Nocardiosis are uncommon. The diagnosis may be difficult, with significant morbidity and mortality, often occurring on frail patients. Few data are available in France. METHODS: A retrospective single center study was conducted from 2002 to 2014 and included all patients with at least one positive microbiological sample for Nocardia with a follow-up in our hospital. RESULTS: Nineteen patients, including 15 men, were included with a mean age of 58 years (25-85). Seventeen had a risk factor (lung diseases [13], corticosteroids [12], solid neoplasia [2], HIV infection [2], diabetes mellitus [3], kidney transplant [2], lymphopenia [1]). Infections' locations were: pulmonary (12), brain (3), skin (2), lymph node (1) and corneal (1). The slow growth leads to a median of 35 days for a positive result (3-95). Nine species were identified. Fifteen patients (79%) received one or more lines of antibiotics including: cotrimoxazole (9), amoxicillin (7) cefotaxime/ceftriaxone (7) imipenem (3), or amikacin (3). The average duration of antibiotic therapy was 207 days. Four patients did not receive antibiotics due to a late result or a bacterial co-infection masking nocardiosis. Five patients died (26%) including 2 with cerebral nocardiosis. Six patients were cured, 4 suffered a relapse, 4 had an unknown evolution, and 1 was still treated. CONCLUSION: Our study shows that nocardiosis is a disease difficult to treat. A better understanding of this type of infection is necessary. PMID- 27659746 TI - [Analysis of the 2015 British guidelines on the prevention and management of tumor lysis syndrome]. AB - Whether it appears spontaneously or is induced by therapy, the tumor lysis syndrome is responsible for a massive release of ions and puric bases degradation of products in the circulation exceeding the renal excretion capacity. Some, such as uric acid, xanthine, and calcium phosphate, can precipitate in the renal tubules or parenchyma. It must be known to any practitioner supporting patients with hematologic malignancies, mainly high-grade but also some solid tumors. The 2015 publication of the British recommendations pertaining to patients suffering from hematological diseases should be broadcast. The main goal of treatment is to prevent the occurrence of renal dysfunction associated with heavy morbidity and mortality, either for his own conduct or consequences on obtaining a good tumor response. Some items proposed for the care, whether curative or preventive, should be discussed or detailed, which is the subject of this paper. PMID- 27659748 TI - Ionotropic glutamate receptors: Still exciting after all these years. PMID- 27659747 TI - Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson's disease. AB - OBJECTIVE: To assess whether functional neural connectivity is disrupted between the regions of the default mode network (DMN) in Parkinson's disease (PD) and how this connectivity is related to cognition, brain gray matter structure and white matter integrity and diffusivity. METHODS: Thirty-seven PD patients and 16 healthy controls were evaluated, using resting-state functional magnetic resonance imaging (MRI), T1-weighted MRI, diffusion-weighted imaging and a battery of cognitive tests. Functional connectivity between the regions of the DMN, specifically in the precuneus, anterior and posterior cingulate, medial prefrontal and temporal and inferior parietal cortices was assessed with seed-to voxel connectivity; gray matter volume and white matter values were determined using voxel-based morphometry and tract-based spatial statistics. RESULTS: Reduced functional connectivity was observed between the posterior cingulate and medial temporal lobe in PD. Lower cognitive performance, gray matter loss in posterior, medial temporal and parietal areas, and fractional anisotropy reduction in the white matter adjacent to DMN regions were also observed in PD patients compared with healthy controls. Lower DMN functional connectivity correlated with lower verbal and visual memory and visual abilities performance in PD. In addition, lower DMN functional connectivity correlated with lower gray matter volume in the posterior cingulate and precuneus, and with lower white matter fractional anisotropy of the inferior longitudinal and posterior cingulate fasciculi in PD. CONCLUSIONS: By combining different neuroimaging techniques and cognitive data, results showed that functional connectivity alteration between the regions of the DMN is associated with lower cognitive performance and gray and white matter abnormalities in PD. PMID- 27659749 TI - The New Careers in Nursing Program: A Strong Investment in the Future of Nursing. AB - In 2008, faced with the challenges of a looming nursing shortage and a nursing workforce that did not mirror the diversity of the population of the United States, the Robert Wood Johnson Foundation considered how to contribute to a solution. A key challenge was how to rapidly and effectively build a cadre of diverse nurses who were ready to take on the leadership challenges of an evolving health care system. From that challenge, the New Careers in Nursing program was developed. A collaboration between the Robert Wood Johnson Foundation and the American Association of Colleges of Nursing, the program set about to change the face of nursing. After investing in over 3,500 scholars and as the program winds down, the program's impact can be seen in the scholars, the schools, the nursing profession, and the future investments of the Robert Wood Johnson Foundation. PMID- 27659750 TI - Dollars and Sense: The Policy Implications of Financing an Accelerated Nursing Degree. AB - The landmark report, The Future of Nursing: Leading Change, Advancing Health set a goal for the nursing community to increase the proportion of nurses with a baccalaureate degree from 50 to 80% by 2020 (Institute of Medicine, 2010). Nursing has witnessed a dramatic growth in the number of enrollments in accelerated baccalaureate of science in nursing programs for nonnursing graduates (Fang, Bednash, & DeWitty, 2012). Financing these degrees can be challenging. Many second-degree students no longer qualify for the federal grant programs and may have exhausted their federal undergraduate loan limits. The population for the current study is made up of accelerated baccalaureate of science in nursing students who received scholarships through the Robert Wood Johnson Foundation (RWJF) New Careers in Nursing (NCIN) Scholarship Program and the schools of nursing they have attended. This is a descriptive study. An analysis of RWJF NCIN scholars' survey responses reveals that while 90% of RWJF NCIN scholars incurred debt to finance their programs, the scholarship makes a difference in helping them to earn their degrees. A review of RWJF NCIN schools of nursing grantee reports establishes that, for many schools of nursing, the recognition and support of an external funding organization helps them to leverage additional funding opportunities. PMID- 27659751 TI - Pedagogy and Academic Success in Prelicensure Nursing Education. AB - The purpose of this article is to provide a brief description of the New Careers in Nursing (NCIN) program; highlight the features of the NCIN Preentry Immersion program designed to help students achieve academic success; introduce two NCIN innovation teaching projects that used active learning strategies to foster student engagement; and conduct an integrative review on the pedagogies used to foster academic success in nursing education. The integrative review revealed that interactive pedagogies fostered student engagement and increased the students' knowledge acquisition, competence, confidence, and satisfaction. Significant variations in the methodological rigor for the studies included in this review were noted in addition to nebulousness between nursing education research and evaluation. The review validated the need for more rigorous research in nursing education to improve the students' academic experience and subsequent success of all nursing students, including those from underrepresented or disadvantaged backgrounds, enrolled in prelicensure nursing education programs. PMID- 27659752 TI - Looking Is Not Seeing and Listening Is Not Hearing: A Replication Study With Accelerated BSN Students. AB - Development of perceptual aptitude is a critical yet complex skill that requires the effective organization and interpretation of data using visual and auditory clinical observation. Educators face challenges in creating pedagogy that consistently demonstrates reliability and validity in fostering clinical skills. We have dependably used the arts as a means to improve students' auditory and visual skills, and this article will describe replication of our work with accelerated nursing students in a bachelor's program in their last semester of nursing school (n=23). Our results reveal that auscultative and observational abilities of soon-to-be registered nurses are in need of improvement. The use of art in a museum improves observational and assessment abilities, and music training increases auscultative interpretive skills significantly. PMID- 27659753 TI - Gaming the System: Developing an Educational Game for Securing Principles of Arterial Blood Gases. AB - This article describes the development process for creating a digital educational mini game prototype designed to provide practice opportunities for learning fundamental principles of arterial blood gases. Mini games generally take less than an hour to play and focus on specific subject matter. An interdisciplinary team of faculty from two universities mentored student game developers to design a digital educational mini game prototype. Sixteen accelerated bachelor of science in nursing students collaborated with game development students and playtested the game prototype during the last semester of their senior year in nursing school. Playtesting is a form of feedback that supports an iterative design process that is critical to game development. A 10-question survey was coupled with group discussions addressing five broad themes of an archetypical digital educational mini game to yield feedback on game design, play, and content. Four rounds of playtesting and incorporating feedback supported the iterative process. Accelerated bachelor of science in nursing student playtester feedback suggests that the digital educational mini game prototype has potential for offering an engaging, playful game experience that will support securing the fundamental principles of arterial blood gases. Next steps are to test the digital educational mini game for teaching and learning effectiveness. PMID- 27659754 TI - New Careers in Nursing: Optimizing Diversity and Student Success for the Future of Nursing. AB - In 2008, the Robert Wood Johnson Foundation collaborated with the American Association of Colleges of Nursing to create the New Careers in Nursing (NCIN) scholarship program. Two goals of the program were to alleviate the nursing shortage and to increase diversity of the workforce. During this 7-year program (i.e., seven funding cycles), 130 schools of nursing in 41 states and the District of Columbia were selected as grantees, and they awarded 3,517 scholarships to second-degree accelerated nursing students who were members of groups underrepresented in nursing or who were economically disadvantaged. This article describes the demographic characteristics of the NCIN students, degree of satisfaction with their learning environment, perceptions of their mentoring experiences, and self-identified facilitators and barriers to program completion. Data sources for this article resulted from three surveys completed by scholars during their academic programs: the beginning, the midpoint, and within 6 months postgraduate. Results of analysis indicated that NCIN scholars are significantly more diverse compared with the national nurse population, and they reported high levels of satisfaction with their learning environments. Student relationships with peers and faculty improved during the period of program enrollment. Faculty support was the greatest facilitator for program completion, and competing priorities of finances and family responsibilities were the greatest challenges. PMID- 27659755 TI - Advancing Diversity in Academic Nursing. AB - : As the world around us evolves and as society becomes increasingly diverse, the demographics of the health professions workforce, including nursing, have been slow to change. Even with influential public relations campaigns sponsored by Johnson & Johnson (2015), pivotal policy reports such as the Institute of Medicine the Future of Nursing: Leading Change, Advancing Health report (Institute of Medicine, 2010), and programs such as the New Careers in Nursing Program funded by the Robert Wood Johnson Foundation/New Careers in Nursing (2015), much work remains if the nursing workforce is to match the demographics of the U.S. POPULATION: Therefore, this article will examine the role that accreditation agencies and innovative programs, such as pipeline programs and academic-service scholarship programs, could play in promoting diversity in the future nursing workforce. PMID- 27659756 TI - Strengthening Cultural Competence in Prenatal Care With a Virtual Community: Building Capacity Through Collaboration. AB - : The purpose of this project was to design, implement, and evaluate a virtual simulation experience (VSE) facilitating student access to diverse cultures and strengthening their ability to provide culturally congruent care. DESIGN: Faculty from two universities collaborated in designing a pre/postnatal VSE with African American and Amish patients. Students viewed patient assessments, interacted with patients, worked in teams to develop culturally appropriate care plans, and engaged in debriefing. Outcomes measurements included Jeffreys' Transcultural Self-Efficacy Test (TSET), researcher developed care plans, and program evaluation. RESULTS: Over 80% (N=141) of the invited students consented. Significant increases occurred in overall and subscale post-TSET scores (P<.001). Care plan mean scores were >=8.82 out of 10 points per category. Students recognized the need to be nonjudgmental in patient care. CONCLUSIONS: This study suggests that VSEs are effective in transcending geographic barriers, gaining access to diverse cultures, and strengthening students' cultural competence. PMID- 27659757 TI - Setting the Stage for Success: Mentoring and Leadership Development. AB - The New Careers in Nursing (NCIN) Program funded by The Robert Wood Johnson Foundation has expanded enrollment in schools of nursing with accelerated nursing programs and increased diversity in the nursing workforce. As the demand for highly educated and skilled nurses continues to grow, accelerated nursing programs are thriving and increasing in number. The growing cadre of nontraditional nursing students has challenged nursing faculty to institute innovative teaching methods to develop accelerated students' leadership skills and to provide mentoring resources for newly licensed nurses to guide the successful and complex transition from the student to professional practice. To support its grantee schools and their scholars, the NCIN National Program office has supported the development and distribution of toolkits and other resources and solicited request for proposals to recognize outstanding contributions. The Program Innovation grants are intended to support nurse faculty educators working to develop and enhance educational projects to implement innovative approaches to accelerated nursing education that can be taken to scale and replicated in a variety of educational settings. The Legacy Award honors a program that describes lasting impact on the school as a result of participation in the NCIN program. Two of these projects are described with emphasis on leadership development and transition to practice. PMID- 27659758 TI - New Careers in Nursing Scholar Alumni Toolkit: Development of an Innovative Resource for Transition to Practice. AB - The transition from student to professional nurse is challenging and may be more difficult for underrepresented minority nurses. The Robert Wood Johnson Foundation New Careers in Nursing (NCIN) program supported development of a toolkit that would serve as a transition-to-practice resource to promote retention of NCIN alumni and other new nurses. Thirteen recent NCIN alumni (54% male, 23% Hispanic/Latino, 23% African Americans) from 3 schools gave preliminary content feedback. An e-mail survey was sent to a convenience sample of 29 recent NCIN alumni who evaluated the draft toolkit using a Likert scale (poor = 1; excellent = 5). Twenty NCIN alumni draft toolkit reviewers (response rate 69%) were primarily female (80%) and Hispanic/Latino (40%). Individual chapters' mean overall rating of 4.67 demonstrated strong validation. Mean scores for overall toolkit content (4.57), usability (4.5), relevance (4.79), and quality (4.71) were also excellent. Qualitative comments were analyzed using thematic content analysis and supported the toolkit's relevance and utility. A multilevel peer review process was also conducted. Peer reviewer feedback resulted in a 6-chapter document that offers resources for successful transition to practice and lays the groundwork for continued professional growth. Future research is needed to determine the ideal time to introduce this resource. PMID- 27659759 TI - Collaborative Student Leadership Conference. AB - In April 2008, the New Careers in Nursing (NCIN) Program launched a collaborative initiative between the American Association of Colleges of Nursing and the Robert Wood Johnson Foundation. One of the main goals of this initiative was to provide leadership development through structured activities for NCIN scholars. In order to meet this goal, 3 participating NCIN schools came together to plan and conduct a collaborative student-focused, scholar-led leadership conference for accelerated nursing students. Admittedly, collaboration among institutions of higher education is sometimes not a standard practice. Although sharing the common goal of preparing future nurses to provide high-quality care, many schools of nursing often compete for scarce resources including recruitment of faculty and students, securing clinical placements, and new graduates and alumni compete for jobs. However, there are advantages to sharing financial and intellectual resources in order to ensure a richer educational experience for NCIN scholars and for all accelerated nursing students. Using the Robert Wood Johnson Foundation monies awarded for our Legacy Project, 3 NCIN program liaisons overseeing accelerated nursing programs in Nebraska met to discuss the advantages and disadvantages related to planning and conducting a collaborative student leadership activity for NCIN scholars and their peer-accelerated nursing students. The program liaisons wanted to establish common goals for the endeavor and ensure the use of approaches that would foster leadership development of the NCIN scholars and establish mechanisms by which the group would create a collaborative environment. Although the 3 collaborating colleges were and continue to be competitors for prospective accelerated students, the benefit of collaborating on a joint leadership development project for the NCIN scholars and their peers was clear. Program liaisons recognized that this opportunity would strengthen leadership development and provide relevant experience for the NCIN scholars and result in a conference for other accelerated nursing students. PMID- 27659760 TI - Diversifying the Pipeline Into Doctoral Nursing Programs: Developing the Doctoral Advancement Readiness Self-Assessment. AB - This article presents the development and psychometric analysis of the Doctoral Readiness Self-Assessment for Doctoral Study. This survey was developed as the first step of a Web-based, on-line mentoring platform for nurses who are considering a doctoral degree program. By identifying and anticipating the predictors and barriers of success in doctoral nursing education, including practical (finances, time, geographical restriction) and personal factors (motivation, attitudes, perceived ability to navigate the application process), students are guided through a self-reflective process to determine readiness. Factor analysis revealed that interest, readiness, and support represent 3 distinct factors that may be used for additional analysis to predict future enrollment in doctoral nursing degree programs. The internal reliability analysis revealed that removing 3 items from the 15-item scale increased Cronbach's alpha from 0.75 to 0.80, and these factors explained 51.25% of variance. The self assessment results can inform faculty's work as they mentor and guide students through the application, admission, and financial support processes for doctoral study. PMID- 27659761 TI - Performance of EQ-5D, howRu and Oxford hip & knee scores in assessing the outcome of hip and knee replacements. AB - BACKGROUND: We aimed to compare the performance of EQ-5D-3 L and howRu, which are short generic patient-reported outcome measures (PROMs), in assessing the outcome of hip and knee replacements, using the Oxford Hip Score (OHS) and the Oxford Knee Scores (OKS) for comparison. METHODS: Outcome was assessed as the difference between pre-surgery and 6-month post-surgery scores. We used a large sample from the NHS PROMs database, which used EQ-5D-3 L, and a small cohort of patients having the same operations collected by MyClinicalOutcomes (MCO), which used howRu. Both cohorts completed the OHS (hips) or the OKS (knees). RESULTS: The change (outcome) between pre-op and post-op scores as measured by howRu was greater than that measured by EQ-5D, relative to that measured by OHS or OKS. For hip replacements, the correlation for change measured by howRu and OHS was r = 0.77 (0.66-0.85). The corresponding correlation for change measured by EQ-5D Index and OHS was r = 0.64 (0.63-0.64). For knee replacements the correlation between change in howRu and OKS was r = 0.86 (0.75-0.92); between EQ-5D Index and OKS r = 0.59 (0.58-0.60). CONCLUSIONS: For hip and knee replacement, the outcome measured by howRu was more highly correlated with that measured by the condition specific Oxford Hip and Knee Scores than were EQ-5D Index or EQ-VAS. The magnitude of change before and after surgery was also greater. PMID- 27659762 TI - Effects of tactile stimulation by fathers on physiological responses and paternal attachment in infants in the NICU: A pilot study. AB - The aims of our pilot study were to test (1) the effectiveness of tactile stimulation by fathers on their infants' physiological responses such as oxygen saturation levels, heart rates (HRs), and respiration rates (RRs) and (2) fathers' perceived levels of attachment to infants in the neonatal intensive care unit (NICU). This was a quasi-experimental design using a control group, which assessed pre- and post-intervention differences via t tests. Twenty neonate father dyads participated in the intervention and 20 neonate-father dyads populated a control group from one general hospital located in South Korea. Infants in the experimental group received tactile stimulation for one 10-minute period per day, for five consecutive days. Overall, we found that tactile stimulation by fathers significantly stabilized infants' physiological status, including oxygen saturation levels, HRs, and RRs (t = 2.138, p = .039; t = 2.348, p = .024; t = -3.461, p = .001, respectively) with effect size ranged 0.67 1.10 and increased paternal attachment levels (t = 3.982, p = .001) with large effect size (1.29). This pilot study suggests that tactile stimulation by the father may be regarded as an important and potentially useful intervention for the care of infants in the NICU. PMID- 27659763 TI - Comparing single- and dual-process models of memory development. AB - This experiment examined single-process and dual-process accounts of the development of visual recognition memory. The participants, 6-7-year-olds, 9-10 year-olds and adults, were presented with a list of pictures which they encoded under shallow or deep conditions. They then made recognition and confidence judgments about a list containing old and new items. We replicated the main trends reported by Ghetti and Angelini () in that recognition hit rates increased from 6 to 9 years of age, with larger age changes following deep than shallow encoding. Formal versions of the dual-process high threshold signal detection model and several single-process models (equal variance signal detection, unequal variance signal detection, mixture signal detection) were fit to the developmental data. The unequal variance and mixture signal detection models gave a better account of the data than either of the other models. A state-trace analysis found evidence for only one underlying memory process across the age range tested. These results suggest that single-process memory models based on memory strength are a viable alternative to dual-process models for explaining memory development. PMID- 27659764 TI - [When a patient falls (asleep) and can't get up: conversion disorder - paraplegia following general anesthesia]. AB - BACKGROUND AND OBJECTIVES: This case report describes the rare occurrence of paraplegia caused by conversion disorder in a woman who received general anesthesia for breast surgery. CASE REPORT: A 46-year-old healthy woman received general anesthesia for excision of a left breast fibroepithelial lesion. In the post-anesthesia care unit, she reported bilateral loss of both sensation and motor function below the knees. Physical signs and symptoms did not correlate with any anatomical or neurological patterns; imaging revealed no abnormalities. Psychiatric consultation was performed wherein familial stressor circumstances were identified, leading to diagnosis and management of conversion disorder. CONCLUSION: Conversion disorder is characterized by alteration of physical function due to expression of an underlying psychological ailment. Its diagnosis requires thorough evaluation including appropriate workup to exclude organic causes. The meshing together of anesthesiology and psychiatry - as demonstrated by this case report - offers an opportunity to highlight important information pertaining to the definition, diagnosis, and management of conversion disorder as it may be encountered in the postanesthesia recovery period. PMID- 27659765 TI - An auxin maximum in the middle layer controls stamen development and pollen maturation in Arabidopsis. AB - Here, we investigated the role of auxin distribution in controlling Arabidopsis thaliana late stamen development. We analysed auxin distribution in anthers by monitoring DR5 activity: at different flower developmental stages; inhibiting auxin transport; in the rpk2-3 and ems1 mutants devoid of middle layer (ML) or tapetum, respectively; and in the auxin biosynthesis yuc6 and perception afb1-3 mutants. We ran a phenotypic, DR5::GUS and gene expression analysis of yuc6rpk2 and afb1rpk2 double mutants, and of 1-N-naphthylphthalamic acid (NPA)-treated flower buds. We show that an auxin maximum, caused by transport from the tapetum, is established in the ML at the inception of late stamen development. rpk2-3 mutant stamens lacking the ML have an altered auxin distribution with excessive accumulation in adjacent tissues, causing non-functional pollen grains, indehiscent anthers and reduced filament length; the expression of genes controlling stamen development is also altered in rpk2-3 as well as in NPA treated flower buds. By decreasing auxin biosynthesis or perception in the rpk2-3 background, we eliminated these developmental and gene expression anomalies. We propose that the auxin maximum in the ML plays a key role in late stamen development, as it ensures correct and coordinated pollen maturation, anther dehiscence and filament elongation. PMID- 27659766 TI - 'Remixing Rasmussen': The evolution of Accimaps within systemic accident analysis. AB - Throughout Jens Rasmussen's career there has been a continued emphasis on the development of methods, techniques and tools for accident analysis and investigation. In this paper we focus on the evolution and development of one specific example, namely Accimaps and their use for accident analysis. We describe the origins of Accimaps followed by a review of 27 studies which have applied and adapted Accimaps over the period 2000-2015 to a range of domains and types of accident. Aside from demonstrating the versatility and popularity of the method, part of the motivation for the review of the use of Accimaps is to address the question of what constitutes a sound, usable, valid and reliable approach to systemic accident analysis. The findings from the review demonstrate continuity with the work carried out by Rasmussen, as well as significant variation (e.g., changes to the Accimap, used of additional theoretical and practice-oriented perspectives on safety). We conclude the paper with some speculations regarding future extension and adaptation of the Accimap approach including the possibility of using hybrid models for accident analysis. PMID- 27659767 TI - Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome. AB - Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1 19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet Biedl syndrome-related renal disease attending the United Kingdom national Bardet Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4-5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10, mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b-5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet-Biedl syndrome and identifies risk factors to be considered in genetic counseling. PMID- 27659768 TI - Development of a novel stirrerliquid/solid microextraction method for the separation and enrichment of trace levels of active compounds in traditional Chinese medicine. AB - A novel stirrer-liquid/solid microextraction method was developed for the separation and enrichment of trace levels of curcumin, bisdemethoxycurcumin, and demethoxycurcumin in Rhizoma Curcumae Longae, Radix Curcumae, and Rhizoma Curcumae before their analysis by high-performance liquid chromatography with ultraviolet detection. In the proposed approach, a magnetic stirrer was immersed in decanol to coat its surface completely with decanol, which was used as an extraction platform. The stirrer coated with decanol is not only a power to agitate the sample solution to constantly update the sample on the stirrer surface but also it can adsorb and extract the target analytes. Some effective parameters, including suitable superficial area of stirrer, extraction solvent, sample phase pH, NaCl concentration, stirring rate, extraction time, sample phase volume, were analyzed and selected. Under the optimal conditions, the linearities are 0.0044-2.20 MUg/mL, detection limits are 0.3-0.6 ng/mL, and the extraction content per unit length and enrichment factors of the target analytes are 6.24 9.71/mm and 589-917, respectively. Also, the stirrer-liquid/solid microextraction mechanism for the extraction and enrichment of the target analytes was analyzed and expounded. The results showed that stirrer-liquid/solid microextraction is a simple, rapid sample pretreatment approach with a high enrichment factor. PMID- 27659769 TI - Niche divergence facilitated by fine-scale ecological partitioning in a recent cichlid fish adaptive radiation. AB - Ecomorphological differentiation is a key feature of adaptive radiations, with a general trend for specialization and niche expansion following divergence. Ecological opportunity afforded by invasion of a new habitat is thought to act as an ecological release, facilitating divergence, and speciation. Here, we investigate trophic adaptive morphology and ecology of an endemic clade of oreochromine cichlid fishes (Alcolapia) that radiated along a herbivorous trophic axis following colonization of an isolated lacustrine environment, and demonstrate phenotype-environment correlation. Ecological and morphological divergence of the Alcolapia species flock are examined in a phylogenomic context, to infer ecological niche occupation within the radiation. Species divergence is observed in both ecology and morphology, supporting the importance of ecological speciation within the radiation. Comparison with an outgroup taxon reveals large scale ecomorphological divergence but shallow genomic differentiation within the Alcolapia adaptive radiation. Ancestral morphological reconstruction suggests lake colonization by a generalist oreochromine phenotype that diverged in Lake Natron to varied herbivorous morphologies akin to specialist herbivores in Lakes Tanganyika and Malawi. PMID- 27659770 TI - The central role of national programme management for the achievement of malaria elimination: a cross case-study analysis of nine malaria programmes. AB - BACKGROUND: A malaria eradication goal has been proposed, at the same time as a new global strategy and implementation framework. Countries are considering the strategies and tools that will enable progress towards malaria goals. The eliminating malaria case-study series reports were reviewed to identify successful programme management components using a cross-case study analytic approach. METHODS: Nine out of ten case-study reports were included in the analysis (Bhutan, Cape Verde, Malaysia, Mauritius, Namibia, Philippines, Sri Lanka, Turkey, Turkmenistan). A conceptual framework for malaria elimination programme management was developed and data were extracted and synthesized. Findings were reviewed at a consultative workshop, which led to a revision of the framework and further data extraction and synthesis. Success factors of implementation, programme choices and changes, and enabling factors were distilled. RESULTS: Decentralized programmes enhanced engagement in malaria elimination by sub-national units and communities. Integration of the malaria programme into other health services was also common. Decentralization and integration were often challenging due to the skill and experience levels of newly tasked staff. Accountability for programme impact was not clarified for most programmes. Motivation of work force was a key factor in maintaining programme quality but there were few clear, detailed strategies provided. Different incentive schemes targeted various stakeholders. Training and supervision, although not well described, were prioritized by most programmes. Multi-sectoral collaboration helped some programmes share information, build strategies and interventions and achieve a higher quality of implementation. In most cases programme action was spurred by malaria outbreaks or a new elimination goal with strong leadership. Some programmes showed high capacity for flexibility through introduction of new strategies and tools. Several case-studies described methods for monitoring implementation quality and coverage; however analysis and feedback to those implementing malaria elimination in the periphery was not well described. Political commitment and sustained financing contributed to malaria programme success. Consistency of malaria programmes depends on political commitment, human and financial resources, and leadership. Operational capacity of the programme and the overall health system structure and strength are also important aspects. CONCLUSIONS: Malaria eradication will require adaptive, well managed malaria programmes that are able to tailor implementation of evidence based strategies, founded upon strong sub-national surveillance and response, with adequate funding and human resources. PMID- 27659771 TI - Species specific exome probes reveal new insights in positively selected genes in nonhuman primates. AB - Nonhuman primates (NHP) are important biomedical animal models for the study of human disease. Of these, the most widely used models in biomedical research currently are from the genus Macaca. However, evolutionary genetic divergence between human and NHP species makes human-based probes inefficient for the capture of genomic regions of NHP for sequencing and study. Here we introduce a new method to resequence the exome of NHP species by a designed capture approach specifically targeted to the NHP, and demonstrate its superior performance on four NHP species or subspecies. Detailed investigation on biomedically relevant genes demonstrated superior capture by the new approach. We identified 28 genes that appeared to be pseudogenized and inactivated in macaque. Finally, we identified 187 genes showing strong evidence for positive selection across all branches of the primate phylogeny including many novel findings. PMID- 27659772 TI - Effect of a randomised exclusive breastfeeding counselling intervention nested into the MINIMat prenatal nutrition trial in Bangladesh. AB - AIM: It is unknown whether maternal malnutrition reduces the effect of counselling on exclusive breastfeeding. This study evaluated the effect of breastfeeding counselling on the duration of exclusive breastfeeding, and whether the timing of prenatal food and different micronutrient supplements further prolonged this duration. METHODS: Pregnant women in Matlab, Bangladesh, were randomised to receive daily food supplements of 600 kcal at nine weeks of gestation or at the standard 20 weeks. They also were allocated to either 30 mg of iron and 400 MUg folic acid, or the standard programme 60 mg of iron and folic acid or multiple micronutrients. At 30 weeks of gestation, 3188 women were randomised to receive either eight breastfeeding counselling sessions or the usual health messages. RESULTS: The median duration of exclusive breastfeeding was 135 days in the counselling group and 75 days in the usual health message group (p < 0.001). Prenatal supplements did not modify the effects of counselling. Women in the usual health message group who were randomised to multiple micronutrients exclusively breastfed for 12 days longer than mothers receiving the standard iron-folate combination (p = 0.003). CONCLUSION: Breastfeeding counselling increased the duration of exclusive breastfeeding by 60 days. This duration was not influenced by the supplements. PMID- 27659773 TI - Molecular mechanisms in atopic eczema: insights gained from genetic studies. AB - Atopic eczema (synonymous with atopic dermatitis) is a common heterogeneous phenotype with a wide spectrum of severity, from mild transient disease to a severe chronic disorder with atopic and non-atopic comorbidities. Eczema is a complex trait, resulting from the interaction of multiple genetic and environmental factors. The skin, as an organ that can be biopsied easily, provides opportunities for detailed molecular genetic analysis. Strategies applied to the investigation of atopic eczema include candidate gene and genome wide studies, extreme phenotypes, and comparative analysis of inflammatory skin diseases. Genetic studies have identified a central role for skin barrier impairment in eczema predisposition and perpetuation; this has brought about a paradigm shift in understanding atopic disease, but specific molecular targets to improve skin barrier function remain elusive. The role of Th2-mediated immune dysfunction is also central to atopic inflammation, and has proved to be a powerful target for biological therapy in atopic eczema. Advances in understanding eczema pathogenesis have provided opportunities for patient stratification, primary prevention, and therapy development, but there remain considerable challenges in the application of this knowledge to optimize benefit for patients with atopic eczema in the era of personalized medicine. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27659774 TI - MicroScope: ChIP-seq and RNA-seq software analysis suite for gene expression heatmaps. AB - BACKGROUND: Heatmaps are an indispensible visualization tool for examining large scale snapshots of genomic activity across various types of next-generation sequencing datasets. However, traditional heatmap software do not typically offer multi-scale insight across multiple layers of genomic analysis (e.g., differential expression analysis, principal component analysis, gene ontology analysis, and network analysis) or multiple types of next-generation sequencing datasets (e.g., ChIP-seq and RNA-seq). As such, it is natural to want to interact with a heatmap's contents using an extensive set of integrated analysis tools applicable to a broad array of genomic data types. RESULTS: We propose a user friendly ChIP-seq and RNA-seq software suite for the interactive visualization and analysis of genomic data, including integrated features to support differential expression analysis, interactive heatmap production, principal component analysis, gene ontology analysis, and dynamic network analysis. CONCLUSIONS: MicroScope is hosted online as an R Shiny web application based on the D3 JavaScript library: http://microscopebioinformatics.org/ . The methods are implemented in R, and are available as part of the MicroScope project at: https://github.com/Bohdan-Khomtchouk/Microscope . PMID- 27659775 TI - Post-directed-self-assembly membrane fabrication for in situ analysis of block copolymer structures. AB - Full characterization of the three-dimensional structures resulting from the directed self-assembly (DSA) of block copolymers (BCP) remains a difficult challenge. Transmission electron microscope (TEM) tomography and resonant soft x ray scattering have emerged as powerful and complementary methods for through film characterization; both techniques require samples to be prepared on specialized membrane substrates. Here we report a generalizable process to implement BCP DSA with density multiplication on silicon nitride membranes. A key feature of the process developed here is that it does not introduce any artefacts or damage to the polymer assemblies as DSA is performed prior to back-etched membrane formation. Because most research and applications of BCP lithography are based on silicon substrates, process variations introduced by implementing DSA on a silicon nitride/silicon stack versus silicon were identified and mitigated. Using full-wafers, membranes were fabricated with different sizes and layouts to enable both TEM and x-ray characterization. Finally, both techniques were used to characterize structures resulting from the DSA of lamella-forming BCP with density multiplication. PMID- 27659776 TI - Cervical Spinal Cord and Dorsal Nerve Root Stimulation for Neuropathic Upper Limb Pain. AB - BACKGROUND: Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain in the lower limbs. Upper limb pain comprises a significant proportion of neuropathic pain patients, but is often difficult to target specifically and consistently with paresthesias. We hypothesized that the use of dorsal nerve root stimulation (DNRS), as an option along with SCS, would help us better relieve pain in these patients. METHODS: All 35 patients trialed with spinal stimulation for upper limb pain between July 1, 2011, and October 31, 2013, were included. We performed permanent implantation in 23/35 patients based on a visual analogue scale pain score decrease of >=50% during trial stimulation. RESULTS: Both the SCS and DNRS groups had significant improvements in average visual analogue scale pain scores at 12 months compared with baseline, and the majority of patients in both groups obtained >=50% pain relief. The majority of patients in both groups were able to reduce their opioid use, and on average had improvements in Short Form-36 quality of life scores. Complication rates did not differ significantly between the two groups. CONCLUSIONS: Treatment with SCS or DNRS provides meaningful long-term relief of chronic neuropathic pain in the upper limbs. PMID- 27659777 TI - Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is known as the most common lymphoid malignancy in the Western world. MicroRNAs (miRNAs) are a class of small noncoding RNAs with pivotal roles in cellular and molecular processes related to different malignancies including CLL. Recently, some studies have shown that miR 192 plays a key role in CLL pathogenesis through increasing CDKN1A/p21 levels, suppression of Bcl-2 and enhancement of wild-type P53 and cell cycle arrest. Forty samples, including 20 patients with CLL, diagnosed in Omid hospital (Isfahan, Iran) and 20 healthy controls were sampled during a period of 4 months. Using real-time PCR method, expression of miR-192 was analyzed in peripheral blood mononuclear cells (PBMCs) of CLL patients in comparison with healthy subjects. In silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-192 in DAVID database to explore possible role of miR-192 in some pathways. The expression of miR-192 was found to be significantly reduced (~2.5-folds) in CLL patients compared with healthy subjects (P=0.002). In silico molecular signaling pathway enrichment analysis detected cell indicated signaling pathway as one of the most statistically relevant pathway with miR-192 targetome. Our findings showed that miR-192 could be a biomarker for early diagnosis of CLL. PMID- 27659778 TI - Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue. AB - The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22 degrees C, while Groups III and IV were reared at 38 degrees C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis. PMID- 27659779 TI - A GPS-Based Methodology to Analyze Environment-Health Associations at the Trip Level: Case-Crossover Analyses of Built Environments and Walking. AB - Environmental health studies have examined associations between context and health with individuals as statistical units. However, investigators have been unable to investigate momentary exposures, and such studies are often vulnerable to confounding from, for example, individual-level preferences. We present a Global Positioning System (GPS)-based methodology for segmenting individuals' observation periods into visits to places and trips, enabling novel life-segment investigations and case-crossover analysis for improved inferences. We analyzed relationships between built environments and walking in trips. Participants were tracked for 7 days with GPS receivers and accelerometers and surveyed with a Web based mapping application about their transport modes during each trip (Residential Environment and Coronary Heart Disease (RECORD) GPS Study, France, 2012-2013; 6,313 trips made by 227 participants). Contextual factors were assessed around residences and the trips' origins and destinations. Conditional logistic regression modeling was used to estimate associations between environmental factors and walking or accelerometry-assessed steps taken in trips. In case-crossover analysis, the probability of walking during a trip was 1.37 (95% confidence interval: 1.23, 1.61) times higher when trip origin was in the fourth (vs. first) quartile of service density and 1.47 (95% confidence interval: 1.23, 1.68) times higher when trip destination was in the fourth (vs. first) quartile of service density. Green spaces at the origin and destination of trips were also associated with within-individual, trip-to-trip variations in walking. Our proposed approach using GPS and Web-based surveys enables novel life-segment epidemiologic investigations. PMID- 27659781 TI - Corrigendum to "Formulation and stabilization of norfloxacin in liposomal preparations" [Eur. J. Pharm. Sci. 91 (2016) 208-215]. PMID- 27659780 TI - To gate or not to gate - dosimetric evaluation comparing Gated vs. ITV-based methodologies in stereotactic ablative body radiotherapy (SABR) treatment of lung cancer. AB - BACKGROUND: To compare retrospectively generated gated plans to conventional internal target volume (ITV)-based plans and to evaluate whether gated radiotherapy provides clinically relevant dosimetric improvements to organs-at risk (OARs). METHODS: Evaluation was performed of 150 stereotactic ablative radiotherapy treatment plans delivered to 128 early-stage (T1-T3 (<5 cm)) NSCLC patients. To generate gated plans, original ITV-based plans were re-optimized and re-calculated on the end-exhale phase and using gated planning target volumes (PTV). Gated and ITV-based plans were produced for 3 * 18 Gy and 4 * 12 Gy fractionation regimens. Dose differences between gated and ITV-based plans were analyzed as a function of both three-dimensional motion and tumor volume. OARs were analyzed using RTOG and AAPM dose constraints. RESULTS: Differences between gated and ITV-based plans for all OAR indices were largest for the 3 * 18 Gy regimen. For this regimen, MLD differences calculated by subtracting the gated values from the ITV-based values (ITV vs. Gated) were 0.10 +/- 0.56 Gy for peripheral island (N = 57), 0.16 +/- 0.64 Gy for peripheral lung-wall seated (N = 57), and 0.10 +/- 0.64 Gy for central tumors (N = 36). Variations in V20 were similarly low, with the greatest differences occurring in peripheral tumors (0.20 +/- 1.17 %). Additionally, average differences (in 2Gy-equivalence) between ITV and gated lung indices fell well below clinical tolerance values for all fractionation regimens, with no clinically meaningful differences observed from the 4 * 12 Gy regimen and rarely for the 3 * 18 Gy regimen (<2 % of cases). Dosimetric differences between gated and ITV-based methods did generally increase with increasing tumor motion and decreasing tumor volume. Dose to ribs and bronchial tree were slightly higher in gated plans compared to ITV-based plans and slightly lower for esophagus, heart, spinal cord, and trachea. CONCLUSIONS: Analysis of 150 SABR-based lung cancer treatment plans did not show a substantial benefit for the gating regimen when compared to ITV-based treatment plans. Small benefits were observed only for the largest tumor motion (exceeding 2 cm) and the high dose treatment regimen (3 * 18 Gy), though these benefits did not appear to be clinically relevant. PMID- 27659782 TI - Sequestration of Proteins by Fatty Acid Coacervates for Their Encapsulation within Vesicles. AB - Encapsulating biological materials in lipid vesicles is of interest for mimicking cells; however, except in some particular cases, such processes do not occur spontaneously. Herein, we developed a simple and robust method for encapsulating proteins in fatty acid vesicles in high yields. Fatty acid based, membrane-free coacervates spontaneously sequester proteins and can reversibly form membranous vesicles upon varying the pH value, the precrowding feature in coacervates allowing for protein encapsulation within vesicles. We then produced enzyme enriched vesicles and show that enzymatic reactions can occur in these micrometric capsules. This work could be of interest in the field of synthetic biology for building microreactors. PMID- 27659783 TI - Stem Cell Therapies for Intracerebral Hemorrhages. AB - BACKGROUND: An insult due to intracerebral hemorrhage (ICH) is critical to patients. So, breakthroughs in ICH treatment are very important. OBJECTIVE: Advances in the stem cell treatment of stroke have been remarkable. And stem cell experimentation on ischemic stroke, however, preceded such work on ICH and did not emphasized ICH therapy. METHOD: We review recent stem cell treatments for ICH, an experimental model of ICH, the medical care of ICH, and several stem cell therapies for ICH along with future prospects. RESULTS: Stem cell therapy for ICH is effective in rodent or animal models. For humans, only a small number of clinical trials have been done, and significant functional recovery was recorded. CONCLUSION: We need to reveal the mechanism of stem cell therapy and develop a reliable, definitive treatment strategy for treatment of ICH. In the future, several types of stem cells will be available for the treatment of ICH. PMID- 27659784 TI - Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes. AB - This study aimed to determine whether the serotonergic modulation, through selective 5-HT2 receptor blockade, restores cardiovascular disturbances in type 1 diabetic rats. Diabetes was induced by alloxan (150 mg/kg, s.c.) and maintained for 4 weeks. 5-HT2 receptor was blocked by sarpogrelate (30 mg/kg.day; 14 days; p.o.). Systolic blood pressure (SBP), heart rate (HR), glycaemia and body weight (BW) were monitored periodically. Animals were sacrificed at the end of the study and the heart, right kidney and thoracic aorta were removed; plasma samples were also obtained. Left ventricular hypertrophy index (LVH) and renal hypertrophy index (RH) were determined. Vascular function was studied in aorta rings; additionally, superoxide anion (O2*-) production (by lucigenin-enhanced chemiluminescence) and lipid peroxidation (by thiobarbituric acid reactive substances assay) were measured. Neither alloxan nor sarpogrelate treatments altered HR, LVH or endothelium-independent relaxation. SBP, glycaemia, BW, RH, O2*- production and lipid peroxidation were significantly altered in diabetic animals compared with controls. Sarpogrelate treatment considerably decreased SBP, RH, O2*- production and lipid peroxidation. Endothelium-dependent relaxation was severely reduced in diabetic animal aortas compared to controls; sarpogrelate treatment markedly improved it. Our outcomes show that selectively blocking 5-HT2 receptors has beneficial effects on impaired cardiovascular parameters in diabetes. PMID- 27659787 TI - RE: frameshift variant FANCL*c.1096_1099dupATTA is not associated with high breast cancer risk. PMID- 27659786 TI - Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and PTPN11): clinical and molecular discrimination. AB - Pathogenic mutations in genes (SASH1 and PTPN11) can cause a rare genetic disorder associated with pigmentation defects and the well-known LEOPARD syndrome, respectively. Both conditions presented with lentiginous phenotypes. The aim of this study was to arrive at definite diagnoses of three Chinese boys with clinically suspected lentigines-related syndromes. ADAR1, ABCB6, SASH1 and PTPN11 were candidate genes for mutational screening. Sanger sequencing was performed to identify the mutations, whereas bioinformatic analysis was used to predict the pathogenicity of novel missense mutations. Two novel mutations c.1537A>C (p.Ser513Arg) and 1527_1530dupAAGT (p.Leu511Lysfs*21) in SASH1 and a common p.Thr468Met mutation in PTPN11 were detected in three pediatric patients with lentiginous phenotypes, respectively. Comparisons between clinical presentations showed that SASH1-related phenotypes can exhibit hyper- and hypopigmentation on the trunk and extremities, similar to dyschromatosis, while scattered cafe au-lait spots usually appeared in PTPN11-related LEOPARD syndrome. Furthermore, the similarity in the clinical presentations of Peutz-Jeghers syndrome, Laugier-Hunziker syndrome, xeroderma pigmentosum, neurofibromatosis type I, suggesting that these conditions should be added into the differential diagnoses of lentiginous phenotypes. PMID- 27659785 TI - Quantitative proteome analysis of colorectal cancer-related differential proteins. AB - PURPOSE: To evaluate a new strategy for profiling proteomic changes in colorectal cancer (CRC). METHODES: We used laser capture microdissection (LCM) to obtain cells from 20 CRC and paired normal mucosal tissues. The differential proteins between the microdissected tumor cells and normal mucosa epithelia were analyzed by acetylation stable isotopic labeling coupled with L linear ion trap Fourier transform ion cyclotron resonance mass spectrometry (LTQ-FT MS). Western blotting was used to assess the differential expression of proteins. We used bioinformatics tools for cluster and ingenuity pathway analysis of the differential proteins. RESULTS: In total, 798 confident proteins were quantified and 137 proteins were differentially expressed by at least twofold, including 67 that were upregulated and 70 that were downregulated in cancer. Two differential proteins, solute carrier family 12 member 2 (SLC12A2) and Ras-related protein Rab 10, were validated by Western blotting, and the results were consistent with acetylation stable isotopic labeling analysis. According to gene ontology analysis, CRC-related differential proteins covered a wide range of subcellular locations and were involved in many biological processes. According to ingenuity pathway analysis of the differential proteins, the most relevant canonical pathway associated with CRC was the 14-3-3-mediated signaling pathway, and seven reliable functional networks including cellular growth and proliferation, amino acid metabolism, inflammatory response, embryonic development, carbohydrate metabolism, cellular assembly and organization, and cell morphology were obtained. CONCLUSIONS: Combination of LCM, acetylation stable isotopic labeling analysis and LTQ-FT MS is effective for profiling proteomic changes in CRC cells. PMID- 27659788 TI - Gastric Perforation due to Giant Trichobezoar in a 13-Year-Old Child. AB - Trichotillomania and trichotillophagia can cause the formation of enormous intragastric hairballs. We report the case of a 13-year-old girl who was brought to the emergency service for evaluation of an acute abdomen. Abdominal CT scanner showed a giant gastric trichobezoar which had to be removed by susombilical laparotomy and transverse gastrotomy. This case illustrates the fairly uncommon perforation risk of these gastric bezoars. PMID- 27659789 TI - ALPPS for Colorectal Liver Metastases. PMID- 27659790 TI - Abdominal Pain due to a Wandering Liver. AB - Wandering liver syndrome is an extremely rare congenital disorder. It is mainly diagnosed within the first years of life. Herein we report the case of a 40-year old woman with hepatoptosis due to the absence of anatomical peritoneal attachments of the liver. Surgical treatment consisted in inserting the floppy right lobe of the liver in a subphrenic retroperitoneal pouch. This original technique provided excellent postoperative result. PMID- 27659791 TI - The Macronova in GRB 050709 and the GRB-macronova connection. AB - GRB 050709 was the first short Gamma-ray Burst (sGRB) with an identified optical counterpart. Here we report a reanalysis of the publicly available data of this event and the discovery of a Li-Paczynski macronova/kilonova that dominates the optical/infrared signal at t>2.5 days. Such a signal would arise from 0.05 r process material launched by a compact binary merger. The implied mass ejection supports the suggestion that compact binary mergers are significant and possibly main sites of heavy r-process nucleosynthesis. Furthermore, we have reanalysed all afterglow data from nearby short and hybrid GRBs (shGRBs). A statistical study of shGRB/macronova connection reveals that macronova may have taken place in all these GRBs, although the fraction as low as 0.18 cannot be ruled out. The identification of two of the three macronova candidates in the I-band implies a more promising detection prospect for ground-based surveys. PMID- 27659792 TI - Three-dimensional rotational angiography in children with an aortic coarctation. AB - BACKGROUND: Children with aortic coarctations (CoA) are increasingly percutaneously treated. Good visualisation of the CoA is mandatory and can be obtained with three-dimensional rotational angiography (3DRA). This study aims to compare the diagnostic and therapeutic additional value of 3DRA with conventional biplane angiography (CA) in children with a CoA. METHODS: Patients undergoing percutaneous treatment of CoA with balloon angioplasty (BA) or stent between 2003 and 2015, were retrospectively reviewed on success rate, complications, radiation and technical settings. Diagnostic quality of CA and 3DRA and additional value of 3DRA were scored. RESULTS: In total, 134 patients underwent 183 catheterisations, 121 CA and 62 3DRA-guided. Median age was 0.52 years in the BA group and 11.19 years in the stent group. 3DRA was superior to CA in displaying the left ventricle (p = 0.008), ascending aorta (p < 0.001), aortic arch (p = 0.005) and coronary arteries (p < 0.001). In the BA group, 3DRA had a significantly higher success rate than CA (100.0 % versus 68.9 %, p = 0.016). All stent interventions were successful. Complication rates did not differ significantly. The median total dose area product did not significantly differ between CA and 3DRA in the BA (27.88 MUGym2/kg versus 15.81 MUGym2/kg, p = 0.275) or stent group (37.34 MUGym2/kg versus 45.24 MUGym2/kg, p = 0.090). 3DRA was of additional value in 96.8 % of the interventions. CONCLUSIONS: 3DRA is superior to CA in diagnostic quality and not associated with increased radiation exposure. It provides high additional value in guiding CoA related interventions. PMID- 27659793 TI - Downregulation of angiotensin type 1 receptor and nuclear factor-kappaB by sirtuin 1 contributes to renoprotection in unilateral ureteral obstruction. AB - Activation of sirtuin 1 (Sirt1) attenuates unilateral ureteral obstruction (UUO) induced inflammation and fibrosis, suggesting that Sirt1 may prevent tubulointerstitial fibrosis. In this study, we explored changes in the expression of Sirt1 in the kidneys of UUO-treated rats and evaluated the effects of Sirt1 activation or inhibition on renal pathology and mediators of UUO pathogenesis, especially angiotensin II and nuclear factor (NF)-kappaB, in rats and rat renal fibroblasts. Sirt1 expression increased in the obstructed kidney but not in the contralateral kidney and was mainly detected in tubulointerstitial cells. Resveratrol, a Sirt1 activator, decreased UUO-induced inflammation and fibrosis, while sirtinol, a Sirt1 inhibitor, enhanced UUO-induced inflammation. UUO increased renal angiotensin type 1 receptor (AT1R), NF-kappaB, monocyte chemotactic protein 1 (MCP-1), and fibronectin expression. Resveratrol attenuated these UUO-induced changes, whereas sirtinol enhanced them, with the exception of fibronectin. In renal fibroblasts, Sirt1 overexpression reduced AT1R and NF kappaB levels, while Sirt1 knockdown had the opposite effects. Sirtinol increased the levels of AT1R, NF-kappaB, MCP-1, and connective tissue growth factor (CTGF), while resveratrol reduced AT1R levels. Our results suggested that Sirt1 inhibited AT1R and NF-kappaB expression in renal fibroblasts and that these mechanisms may play roles in alleviating UUO-induced damages. PMID- 27659794 TI - Carbon nanotube-based self-adhesive polymer electrodes for wireless long-term recording of electrocardiogram signals. AB - In this study, the concept of polymer electrodes integrated with a wireless electrocardiogram (ECG) system was described. Polymer electrodes for long-term ECG measurements were fabricated by loading high content of carbon nanotubes (CNTs) in polydimethylsiloxane. Silver nanoparticles (Ag NPs) were added to increase the flexibility of the polymer and the conductivity of the electrode. An ECG electrode patch was fabricated by integrating the electrodes with an adhesive polydimethylsiloxane (aPDMS) layer. Holes in the electrode filled with aPDMS can enable robust contact between the electrode and skin, reducing motion artifacts. A wireless ECG measurement system was developed and adapted to the polymer electrodes. The polymer electrodes combined with the measurement system were successfully applied in wireless, long-term recording of ECG signals. An eleven day continuous test showed that the ECG signal did not degrade over time. The results of attach/detach tests demonstrated that the ECG signal was affected by motion artifacts after six attach/detach cycles. The electrodes produced are flexible and exhibit good ECG performance, and therefore can be used in wearable medical monitoring systems. The approach proposed in this study holds significant promise for commercial application in medical fields. PMID- 27659796 TI - Ultrahigh Responsivity-Bandwidth Product in a Compact InP Nanopillar Phototransistor Directly Grown on Silicon. AB - Highly sensitive and fast photodetectors can enable low power, high bandwidth on chip optical interconnects for silicon integrated electronics. III-V compound semiconductor direct-bandgap materials with high absorption coefficients are particularly promising for photodetection in energy-efficient optical links because of the potential to scale down the absorber size, and the resulting capacitance and dark current, while maintaining high quantum efficiency. We demonstrate a compact bipolar junction phototransistor with a high current gain (53.6), bandwidth (7 GHz) and responsivity (9.5 A/W) using a single crystalline indium phosphide nanopillar directly grown on a silicon substrate. Transistor gain is obtained at sub-picowatt optical power and collector bias close to the CMOS line voltage. The quantum efficiency-bandwidth product of 105 GHz is the highest for photodetectors on silicon. The bipolar junction phototransistor combines the receiver front end circuit and absorber into a monolithic integrated device, eliminating the wire capacitance between the detector and first amplifier stage. PMID- 27659797 TI - Neuro sweet syndrome: a systematic review. A rare complication of Sweet syndrome. AB - Sweet's syndrome (SS) is an inflammatory disease characterized by fever, leucocytosis and distinctive skin lesions that histologically consist of a dermal infiltrate of neutrophils with nuclear fragmentation. Aseptic neutrophilic inflammation may occur also in other organs. Central nervous system involvement in SS, Neuro-Sweet's syndrome (NSS), is rare and reported especially among Asian patients. A systematic review of the literature has been performed to find articles reporting cases of SS with neurological involvement. The search terms: "Sweet's syndrome/disease with neurological involvement, Neuro Sweet Syndrome/Disease" were used in the Pubmed Database. Sixty-nine NSS patients including 46 males and 23 females, more Asian than Caucasian, have been described from 1983 to date. The average age was 48.7 year-old. The most representative neurologic symptom was the altered state of consciousness, followed by headache and memory disorders. Differently from SS with skin or other district involvement, NSS appears to be more common in Asian patients than in Caucasian ones and affects mainly the male sex in the third or fourth decade of life. A very wide range of symptoms and signs can occur, depending on which part of the nervous system is affected. Initial presentation is usually with the SS typical skin lesions followed by neurological involvement. However, also an opposite presentation or a simultaneous skin and nervous involvement may happen. Awareness of the possible neurological complications in SS is important to avoid unnecessary therapies for other forms of meningoencephalitis and lead to successful treatment with systemic corticosteroids. PMID- 27659795 TI - Is monocyte- and macrophage-derived tissue transglutaminase involved in inflammatory processes? AB - Monocytes and macrophages are key players in inflammatory processes following an infection or tissue damage. Monocytes adhere and extravasate into the inflamed tissue, differentiate into macrophages, and produce inflammatory mediators to combat the pathogens. In addition, they take up dead cells and debris and, therefore, take part in the resolution of inflammation. The multifunctional enzyme tissue Transglutaminase (TG2, tTG) is known to participate in most of those monocyte- and macrophage-mediated processes. Moreover, TG2 expression and activity can be regulated by inflammatory mediators. In the present review, we selectively elaborate on the expression, regulation, and contribution of TG2 derived from monocytes and macrophages to inflammatory processes mediated by those cells. In addition, we discuss the role of TG2 in certain pathological conditions, in which inflammation and monocytes and/or macrophages are prominently present, including atherosclerosis, sepsis, and multiple sclerosis. Based on the studies and considerations reported in this review, we conclude that monocyte- and macrophage-derived TG2 is clearly involved in various processes contributing to inflammation. However, TG2's potential as a therapeutic target to counteract the possible detrimental effects or stimulate the potential beneficial effects on monocyte and macrophage responses during inflammation should be carefully considered. Alternatively, as TG2-related parameters can be used as a marker of disease, e.g., in celiac disease, or of disease-stage, e.g., in cancer, we put forward that this could be subject of research for monocyte- or macrophage derived TG2 in inflammatory diseases. PMID- 27659798 TI - Does Expectation of Abnormality Affect the Search Pattern of Radiologists When Looking for Pulmonary Nodules? AB - This experiment investigated whether there might be an effect on the visual search strategy of radiologists during image interpretation of the same adult chest radiographs when given different clinical information. Each of 17 experienced radiologists was asked to interpret a set of 57 (10 abnormal) posteroanterior chest images to identify the presence of pulmonary lesions using differing clinical information (leading to unknown, low and high expectations of prevalence). Eye position metrics (search time, dwell time and time to first fixation) were compared for normal and abnormal images, as well as between conditions. For all images, there was a significantly longer search time at high prevalence expectation compared to low prevalence expectation (W = 75.19, P = <0.0001). Mann-Whitney analysis of the abnormal images demonstrated that the dwell time on correctly identified lesions was significantly shorter at low prevalence expectation compared to both unknown (U = 364.5, P = 0.02) and high prevalence expectation (U = 397.0, P = 0.0002). Visual search patterns of radiologists appear to be affected by changing a priori information where such information fosters an expectation of abnormality. PMID- 27659799 TI - Genome-wide long non-coding RNA screening, identification and characterization in a model microorganism Chlamydomonas reinhardtii. AB - Microalgae are regarded as the most promising biofuel candidates and extensive metabolic engineering were conducted but very few improvements were achieved. Long non-coding RNA (lncRNA) investigation and manipulation may provide new insights for this issue. LncRNAs refer to transcripts that are longer than 200 nucleotides, do not encode proteins but play important roles in eukaryotic gene regulation. However, no information of potential lncRNAs has been reported in eukaryotic alga. Recently, we performed RNA sequencing in Chlamydomonas reinhardtii, and obtained totally 3,574 putative lncRNAs. 1440 were considered as high-confidence lncRNAs, including 936 large intergenic, 310 intronic and 194 anti-sense lncRNAs. The average transcript length, ORF length and numbers of exons for lncRNAs are much less than for genes in this green alga. In contrast with human lncRNAs of which more than 98% are spliced, the percentage in C. reinhardtii is only 48.1%. In addition, we identified 367 lncRNAs responsive to sulfur deprivation, including 36 photosynthesis-related lncRNAs. This is the first time that lncRNAs were explored in the unicellular model organism C. reinhardtii. The lncRNA data could also provide new insights into C. reinhardtii hydrogen production under sulfur deprivation. PMID- 27659800 TI - Dual-Wavelength Terahertz Metasurfaces with Independent Phase and Amplitude Control at Each Wavelength. AB - We have designed, fabricated and characterized dual-wavelength metasurfaces that function at two assigned terahertz wavelengths with independent phase and amplitude control at each wavelength. Specifically, we have designed a dual wavelength achromatic metasurface-based deflector deflecting the incident wave to the same direction at two selected wavelengths, which has circumvented the critical limitation of strong wavelength dependence in the planar metasurface based devices caused by the resonant nature of the plasmonic structures. As a proof of concept demonstration, the designed dual-wavelength achromatic deflector has been fabricated, and characterized experimentally. The numerical simulations, theoretical predictions, and experimental results agree very well with each other, demonstrating the property of independently manipulating the phase profiles at two wavelengths. Furthermore, another unique feature of the designed metasurface is that it can independently tailor both the phase and amplitude profiles at two wavelengths. This property has been numerically validated by engineering a metasurface-based device to simultaneously generate two diffraction orders at two desired wavelengths. PMID- 27659801 TI - Nanometer Scale Scanning Electrochemical Microscopy Instrumentation. AB - We report the crucial components required to perform scanning electrochemical microscopy (SECM) with nanometer-scale resolution. The construction and modification of the software and hardware instrumentation for nanoscale SECM are explicitly explained including (1) the LabVIEW code that synchronizes the SECM tip movement with the electrochemical response, (2) the construction of an isothermal chamber to stabilize the nanometer scale gap between the tip and substrate, (3) the modification of a commercial bipotentiostat to avoid electrochemical tip damage during SECM experiments, and (4) the construction of an SECM stage to avoid artifacts in SECM images. These findings enabled us to successfully build a nanoscale SECM, which can be utilized to map the electrocatalytic activity of individual nanoparticles in a typical ensemble sample and study the structure/reactivity relationship of single nanostructures. PMID- 27659803 TI - Complete resection for pleomorphic lung cancer with a high serum IL-6 level: a case report. AB - BACKGROUND: Pleomorphic lung cancer cells have been reported to produce cytokines, resulting in systemic reactions. Recently, the autonomous production of hematopoietic cytokines (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-6 [IL 6]) was observed in some of these patients. CASE PRESENTATION: We herein report a case of complete resection of right pleomorphic lung cancer producing IL-6. The patient had a high-grade fever before surgery, and a blood examination showed high IL-6 and CRP levels in the serum. After surgery, the patient no longer had a fever, and the elevated serum IL-6 levels had dropped to values less than those before the operation. Immunohistochemically, the carcinoma cells were faintly or focally positive for IL-6 and negative for G-CSF. CONCLUSIONS: The symptoms in the present case were dramatically improved by surgery. In addition, an immunohistochemical examination showed that the cancer cells were positive for IL 6. PMID- 27659802 TI - Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)-Targeted Photothermal Therapy. AB - Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy. PMID- 27659805 TI - A Case Report of Penile Infection Caused by Fluconazole- and Terbinafine Resistant Candida albicans. AB - Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. However, balanoposthitis caused by fluconazole- and terbinafine-resistant Candida albicans has rarely been reported. Here, we describe a case of a recurrent penile infection caused by fluconazole- and terbinafine-resistant Candida albicans, as well as the treatments administered to this patient. The isolate from the patient was tested for drug susceptibility in vitro. It was sensitive to itraconazole, voriconazole, clotrimazole and amphotericin B, but not to terbinafine and fluconazole. Thus, oral itraconazole was administrated to this patient with resistant Candida albicans penile infection. The symptoms were improved, and mycological examination result was negative. Follow-up treatment of this patient for 3 months showed no recurrence. PMID- 27659804 TI - Flavonoid constituents of Dobera glabra leaves: amelioration impact against CCl4 induced changes in the genetic materials in male rats. AB - CONTEXT: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations. OBJECTIVE: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials. MATERIALS AND METHODS: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200 mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl4 (0.5 mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats. RESULTS: Isorhamnetin-3-O-beta-glucopyranoside-7-O-alpha rhamnopyranoside, isorhamnetin-3-O-alpha-rhamnopyranoside-7-O-beta glucopyranoside, kaempferol-3,7-di-O-alpha-rhamnopyranoside, isorhamnetin-3-O beta-glucopyranoside, kaempferol-3-O-beta-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200 mg/kg bw) + CCl4 exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl4, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8 U/mg protein/min compared to CCl4 (1.8 U/mg protein/min). DISCUSSION AND CONCLUSION: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity. PMID- 27659807 TI - Double-Tailed Cystine Derivatives as Novel Substitutes of Phospholipids with Special Reference to Liposomes. AB - Cystine-based gemini surfactants with dodecyl, tetradecyl, hexadecyl, and octadecyl hydrocarbon chains were synthesized, and their interactions with unsaturated (soy phosphatidylcholine, SPC)/saturated (hydrogenated SPC, HSPC) soy phosphatidylcholines in the forms of a monolayer and a model liposome were estimated for different combinations of the components in the mixed systems. Studies of Langmuir monolayers at the air-aqueous buffer interface revealed condensation of the monomolecular films with the addition of surfactants. The effect of surfactants decreased according to the following order: octadecyl > hexadecyl > tetradecyl > dodecyl homologs. The nonideal mixing between the components was estimated using the deviation of the experimental molecular area from the ideal area per molecule. The excess molecular area increased with the increase in the surfactant chain length and phospholipid saturation. The 50 mol % mixture of cystine derivatives and phospholipids formed thermodynamically stable monolayers. The surfactants increased the rigidity of SPC monolayers and decreased that of HSPC monolayers, as observed by the studies of surface dialational rheology. The film structure at the air-water interface could differentiate the SPC- and HSPC-comprising systems through the formation of organized regions, especially at a higher surface pressure. The constriction of surfactant/phospholipid hybrid vesicles was observed with an increase in the length of surfactant hydrocarbon chains. The negative zeta potential of vesicles took the highest values and did not change with time for 20 and 50 mol % surfactant. The spherical shape of the vesicles was confirmed by transmission electron microscopy. Differential scanning calorimetry revealed an increase in fluidity of HSPC bilayers and rigidity of SPS bilayers under the influence of surfactants. These effects were confirmed by fluorescence spectroscopy. All of the vesicle formulations were found to be nontoxic from the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, suggesting their potential as a novel membranous system for the delivery of drugs, genetic materials, vaccines, and other therapeutic agents. PMID- 27659806 TI - The Role of Phagocytes and NETs in Dermatophytosis. AB - Innate immunity is the host first line of defense against pathogens. However, only in recent years, we are beginning to better understand the ways it operates. A key player is this branch of the immune response that are the phagocytes, as macrophages, dendritic cells and neutrophils. These cells act as sentinels, employing specialized receptors in the sensing of invaders and host injury, and readily responding to them by production of inflammatory mediators. They afford protection not only by ingesting and destroying pathogens, but also by providing a suitable biochemical environment that shapes the adaptive response. In this review, we aim to present a broad perspective about the role of phagocytes in dermatophytosis, focusing on the mechanisms possibly involved in protective and non-protective responses. A full understanding of how phagocytes fit in the pathogenesis of these infections may open the venue for the development of new and more effective therapeutic approaches. PMID- 27659808 TI - Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis. AB - OBJECTIVES: This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis. METHODS: Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n = 49) or traditional bisphosphonates (n = 49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment. RESULTS: There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate. CONCLUSIONS: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis. PMID- 27659809 TI - Polymorphic variants of MRP4/ABCC4 differentially modulate the transport of methylated arsenic metabolites and physiological organic anions. AB - Broad inter-individual variation exists in susceptibility to arsenic-induced tumours, likely involving differences in the ability of individuals to eliminate this metalloid. We recently identified human multidrug resistance protein 4 (MRP4/ABCC4) as a novel pathway for the cellular export of dimethylarsinic acid (DMAV), the major urinary arsenic metabolite in humans, and the diglutathione conjugate of the highly toxic monomethylarsonous acid [MMA(GS)2]. These findings, together with the basolateral and apical membrane localization of MRP4 in hepatocytes and renal proximal tubule cells, respectively, suggest a role for MRP4 in the urinary elimination of hepatic arsenic metabolites. Accordingly, we have now investigated the influence of non-synonymous single nucleotide polymorphisms (SNPs) on MRP4 levels, cellular localization, and arsenical transport. Of eight MRP4 variants (C171G-, G187W-, K304N-, G487E-, Y556C-, E757K , V776I- and C956S-MRP4) characterized, two (V776I- and C956S-MRP4) did not localize appropriately to the plasma membrane of HEK293T and LLC-PK1 cells. Characterization of the six correctly localized mutants revealed that MMA(GS)2 transport by C171G-, G187W-, and K304N-MRP4 was 180%, 73%, and 30% of WT-MRP4 activity, respectively, whereas DMAV transport by K304N- and Y556C-MRP4 was 30% and 184% of WT-MRP4, respectively. Transport of the prototypical physiological MRP4 substrates prostaglandin E2 and 17beta-estradiol 17-(beta-d-glucuronide) by the six variants was also differentially affected. Thus, MRP4 variants have differing abilities to transport arsenic and endogenous metabolites through both altered function and membrane localization. Further investigation is warranted to determine if genetic variations in ABCC4 contribute to inter-individual differences in susceptibility to arsenic-induced (and potentially other) diseases. PMID- 27659810 TI - Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology. AB - The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Deltapsim) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r=0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100MUM. These compounds could, therefore, have some therapeutic potential in a clinical setting. PMID- 27659812 TI - Drug candidates and model systems in respiratory syncytial virus antiviral drug discovery. AB - The development of antiviral strategies to prevent or treat respiratory syncytial virus (RSV) infections is of great importance, especially considering the fact that RSV is one of the most important causes of pediatric respiratory infections. However, despite intense efforts, there is no antiviral or vaccine approved for the prevention or treatment of RSV infections. Several inhibitors, targeting different RSV proteins have been discovered over the past decade. We here review the most important chemical series as well as recent developments in understanding which viral proteins and/or host cell factors are good targets for inhibition of viral replication. In addition, we highlight the current in vitro and in vivo model systems of the disease. A number of molecules are currently in (advanced) preclinical or clinical development. Significant breakthroughs in the field may be expected in the upcoming years. PMID- 27659811 TI - Pharmacological inhibition of arginine and lysine methyltransferases induces nuclear abnormalities and suppresses angiogenesis in human endothelial cells. AB - Posttranslational modifications of histone tails can alter chromatin structure and regulate gene transcription. While recent studies implicate the lysine/arginine protein methyltransferases in the regulation of genes for endothelial metabolism, the role of AMI-1 and AMI-5 compounds in angiogenesis remains unknown. Here, we show that global inhibition of arginine and lysine histone methyltransferases (HMTs) by AMI-5 induced an angiostatic profile in human microvascular endothelial cells and human umbilical vein endothelial cells. Based on FACS analysis, we found that inhibition of HMTs significantly affects proliferation of endothelial cells, by suppressing cell cycle progression in the G0/G1 phase. Immunofluorescent studies of the endothelial cells replication pattern by 5-ethynyl-2'-deoxyuridine incorporation disclosed that AMI-5, and the arginine methyltransferase inhibitor AMI-1, induced heterochromatin formation and a number of nuclear abnormalities, such as formation of micronuclei (MNs) and nucleoplasmic bridges (NPBs), which are markers of chromosomal instability. In addition to the modification of the cell cycle machinery in response to AMIs treatment, also endothelial cells migration and capillary-like tube formation processes were significantly inhibited, implicating a stimulatory role of HMTs in angiogenesis. PMID- 27659813 TI - The Medial Extra-Sellar Corridor to the Cavernous Sinus: Anatomic Description and Clinical Correlation. AB - OBJECTIVE: The zenith of surgical interest in the cavernous sinus peaked in the 1980s, as evidenced by reports of 10 surgical triangles that could access the contents of the lateral sellar compartment (LSC). However, these transcranial approaches later became marginalized, first by radiosurgery's popularity and lower morbidity, and then by clinical potential of endoscopic corridors noted in several qualitative studies. Our anatomic study, taking a contemporary look at the medial extra-sellar corridor, gives a detailed qualitative-quantitative analysis for its use with increasingly popular endoscopic endonasal approaches to the cavernous sinus. METHODS: In 20 cadaveric specimens, we re-examined the anatomic landmarks of the medial corridor into the LSC with qualitative descriptions and measurements. An illustrative case highlights a recurrent symptomatic pituitary adenoma that invaded the cavernous sinus approached through the medial corridor. RESULTS: The corridor's shape varied from tetrahedron to hexahedron. Comparing right and left sides, width averaged 3.6 +/- 4.5 mm and 4.0 +/- 4.4 mm, and height averaged 2.3 mm and 2.1 mm, respectively. About 35% of sides showed ample space for access into the cavernous sinus. Our case report of successful outcome lends support for the safety and efficacy of this endoscopic approach. CONCLUSIONS: Our re-examination of this particular surgical access into the LSC refines the understanding of the medial extra-sellar corridor as a main endoscopic access route to this compartment. Achieving safe access to the contents of the LSC, this 11th triangle is clinically relevant and potentially superior for select lesions in this region. PMID- 27659814 TI - Application of a Compact High-Definition Exoscope for Illumination and Magnification in High-Precision Surgical Procedures. AB - BACKGROUND: The basic necessities for surgical procedures are illumination, exposure, and magnification. These have undergone transformation in par with technology. One of the recent developments is the compact magnifying exoscope system. In this report, we describe the application of this system for surgical operations and discuss its advantages and pitfalls. METHODS: We used the ViTOM exoscope mounted on the mechanical holding arm. The following surgical procedures were conducted: lumbar and cervical spinal canal decompression (n = 5); laminotomy and removal of lumbar migrated disk herniations (n = 4); anterior cervical diskectomy and fusion (n = 1); removal of intraneural schwannomas (n = 2); removal of an acute cerebellar hemorrhage (n = 1); removal of a parafalcine atypical cerebral hematoma caused by a dural arteriovenous fistula (n = 1); and microsutures and anastomoses of a nerve (n = 1), an artery (n = 1), and veins (n = 2). RESULTS: The exoscope offered excellent, magnified, and brilliantly illuminated high-definition images of the surgical field. All surgical operations were successfully completed. The main disadvantage was the adjustment and refocusing using the mechanical holding arm. The time required for the surgical operation under the exoscope was slightly longer than the times required for a similar procedure performed using an operating microscope. CONCLUSIONS: The magnifying exoscope is an effective and nonbulky tool for surgical procedures. In visualization around the corners, the exoscope has better potential than a microscope. With technical and technologic modifications, the exoscope might become the next generation in illumination, visualization, exposure, and magnification for high-precision surgical procedures. PMID- 27659815 TI - Intracranial Cystic Myofibroblastoma: a Case Report with Literature Review. AB - BACKGROUND: Myofibroblastoma is a rare benign soft tissue tumor comprised of contractile myiod cells mostly in mammary gland. Only 4 prior cases arising in the central nervous system have been reported in the literature. We present a case of myofibroblastoma with a cystic component. CASE DESCRIPTION: The patient is a 76-year-old man with a history of Parkinson disease. The tumor was found incidentally after a minor fall. Magnetic resonance imaging revealed a 6.7-cm well-circumscribed, partly cystic mass with a 2.4-cm calcified central nodule located at the left sylvian fissure. The frontal dural base showed avid enhancing after gadolinium injection. Gross total resection was achieved. The tumor was marked by dense collagenous tissue and bland spindled cells in pathology review. The spindled cells demonstrated positive staining with antibodies to CD34, estrogen receptor, and smooth muscle actin. A blush of immunoreactivity is observed in scattered cells with antibody to progesterone receptor. Patient recovered well postoperatively. CONCLUSIONS: This is a rare condition of a benign soft tissue tumor of mammary gland presented primarily in the brain. The literature on myofibroblastomas arising in the central nervous system is reviewed. PMID- 27659817 TI - Volume determination of irregularly-shaped quasi-spherical nanoparticles. AB - Nanoparticles (NPs) are widely used in diverse application areas, such as medicine, engineering, and cosmetics. The size (or volume) of NPs is one of the most important parameters for their successful application. It is relatively straightforward to determine the volume of regular NPs such as spheres and cubes from a one-dimensional or two-dimensional measurement. However, due to the three dimensional nature of NPs, it is challenging to determine the proper physical size of many types of regularly and irregularly-shaped quasi-spherical NPs at high-throughput using a single tool. Here, we present a relatively simple method that determines a better volume estimate of NPs by combining measurements from their top-down projection areas and peak heights using two tools. The proposed method is significantly faster and more economical than the electron tomography method. We demonstrate the improved accuracy of the combined method over scanning electron microscopy (SEM) or atomic force microscopy (AFM) alone by using modeling, simulations, and measurements. This study also exposes the existence of inherent measurement biases for both SEM and AFM, which usually produce larger measured diameters with SEM than with AFM. However, in some cases SEM measured diameters appear to have less error compared to AFM measured diameters, especially for widely used IS-NPs such as of gold, and silver. The method provides a much needed, proper high-throughput volumetric measurement method useful for many applications. Graphical Abstract The combined method for volume determination of irregularly-shaped quasi-spherical nanoparticles. PMID- 27659816 TI - Development of monoclonal antibody-based sensitive ELISA for the determination of Cry1Ie protein in transgenic plant. AB - Cry1Ie is a kind of Bacillus thuringiensis (Bt) toxin protein which has a different action model than the Cry1Ab and Cry1Ac protein. The transgenic maize expressing Cry1Ie might be commercially used in the near future and it is urgent to develop a method to detect Cry1Ie protein in transgenic plants and their products. To develop an ELISA method, Cry1Ie protein was expressed in Escherichia coli strain Transetta DE3, purified with the Ni-NTA spin columns, and then validated by sequencing. Bioassay results showed that the purified Cry1Ie protein was highly toxic to the Asian corn borer. The polyclonal antibody (pAb) and the specific monoclonal antibody (mAb) 1G42D6 were generated from rabbit and mice which were immunized with Cry1Ie protein, respectively. Western blotting of crude Cry1Ie protein extracts was established by employing mAb 1G42D6, whereas the mAb 1G42D6 negligibly recognized other Bt proteins. Sandwich ELISA against Cry1Ie protein was established by coating with pAb and detecting with mAb 1G42D6. The limit of detection (LOD), the limit of quantification (LOQ), and the quantification range of the assay in different matrices of maize plant were determined as 0.27-0.51, 0.29-0.78, and 0.45-15.71 ng/mL, respectively. Recoveries of Cry1Ie protein spiked in different maize tissues ranged from 75.1 to 99.5 %. The established sandwich ELISA was verified using transgenic maize overexpressing Cry1Ie. The results in this study suggested that the established ELISA method is effective for detecting Cry1Ie protein in transgenic plants. PMID- 27659818 TI - Presidential address (ISPN 2015, Izmir). PMID- 27659820 TI - The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children. : Part II: age related ONSD cut-off values and patency of the anterior fontanelle. AB - PURPOSE: To analyse the diagnostic accuracy of age-related optic nerve sheath diameter (ONSD) cut-off values in children for detecting raised intracranial pressure (ICP) and to assess the benefit of using patency of the anterior fontanelle in describing a different set of cut-off values. METHODS: The ONSD measurement was performed prior to invasive ICP measurement in children under general anesthesia. The diagnostic accuracy of the ONSD measurement was compared to ICP at thresholds of 20, 15, 10, and 5 mmHg. This was further analysed in children above and below the age of 1 year, with a subgroup analysis of age at 4 years, and assessment of the anterior fontanelle (AF) as a reliable physiological marker in part II of this study. RESULTS: Data from 174 children were analysed. In children <=1 year old, the ONSD measurement with the best diagnostic accuracy for detecting ICP >= 20 mmHg was 5.16 mm, compared to 5.75 mm in children >1 year old (p < 0.001). In addition, patency of the anterior fontanelle (AF) was found to be a useful clinical marker for defining different ONSD cut-off values at ICP thresholds of 20, 15, 10 and 5 mmHg. CONCLUSION: Transorbital ultrasound measurement of the ONSD is a reliable non-invasive marker of ICP particularly at higher thresholds of 20 and 15 mmHg. Patency of the AF is a useful clinical marker for defining different ONSD cut-off values in children. PMID- 27659821 TI - Hemispheric low-grade gliomas. PMID- 27659819 TI - The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children : Part I: repeatability, observer variability and general analysis. AB - PURPOSE: The aim of this study was to investigate the relationship between optic nerve sheath diameter (ONSD) measurement and invasively measured intracranial pressure (ICP) in children. METHODS: ONSD measurement was performed prior to invasive measurement of ICP. The mean binocular ONSD measurement was compared to the ICP reading. Physiological variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate, temperature, respiratory rate and end tidal carbon dioxide (ETCO2) level were recorded at the time of ONSD measurement. Diagnostic accuracy analysis was performed at various ICP thresholds and repeatability, intra- and inter-observer variability, correlation between measurements in different imaging planes as well the relationship over the entire patient cohort were examined in part I of this study. RESULTS: Data from 174 patients were analysed. Repeatability and intra observer variability were excellent (alpha = 0.97-0.99). Testing for inter observer variability revealed good correlation (r = 0.89, p < 0.001). Imaging in the sagittal plane demonstrated a slightly better correlation with ICP (r = 0.66, p < 0.001). The ONSD measurement with the best diagnostic accuracy for detecting an ICP >= 20 mmHg over the entire patient cohort was 5.5 mm, sensitivity 93.2 %, specificity 74 % and odds ratio (OR) of 39.3. CONCLUSION: Transorbital ultrasound measurement of the OSND is a reliable and reproducible technique, demonstrating a good relationship with ICP and high diagnostic accuracy for detecting raised ICP. PMID- 27659823 TI - Cerebral hemispheric low-grade glial tumors in children: preoperative anatomic assessment with MRI and DTI. AB - PURPOSE: The aims of this study are to analyze how the nature and the behavior of low-grade glial tumors (LGGT) in children may correlate with the anatomy of the cerebral hemispheres and to evaluate the consequent impact of diffusion tensor imaging (DTI) techniques in the presurgical assessment. METHODS: This is a combined review of a series of 155 cases of LGGT and of the recent literature on the subject. RESULTS: The cases retrieved from our data bank were divided in central hemispheric tumors (basal ganglia and thalami) (36 cases), glioneuronal cortical-based tumors (49 cases), and glial tumors of the cerebral mantle (70 cases). A close correlation was found in the thalamus between the primary location of the tumor (juxta-ventricular, inferior, lateral, bilateral) and its extension (ventricular lumen, midbrain and mesial temporal, globus pallidus, respectively) which may relate to the connectivity. Among the glioneuronal tumors, most gangliogliomas were located in the temporal lobe and especially in the mesial temporal structures. In addition, the morphologic feature of the ganglioglioma was different there from the neocortical areas. As a complementary approach, DTI data may assist in evaluating the structure and the extension of the LGGT, in addition to planning the surgical strategy. CONCLUSIONS: In the cerebral hemispheres like in the rest of the central nervous system, there is some degree of correlation between the anatomy and the nature, appearance, and behavior of the LGGT in children. PMID- 27659822 TI - An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update. AB - Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies. The recent literature about hemispheric PLGGs was reviewed to provide an up-to-date overview of the molecular and cell biology of these tumors. Hemispheric PLGGs can harbor multiple alterations involving BRAFV600E, FGFR, NTRK, MYB/MYBL1, IDH, and BRAF KIAA1549 fusions. However, the clinical significance of most of these alterations is still to be defined. The role of RAS/MAPK mutations and other alterations in hemispheric PLGGs is of interest from diagnostic, prognostic, and therapeutic perspectives. Molecular testing for these tumors should be encouraged, since the findings can have an important impact not only in prognosis but also in therapeutic strategies. PMID- 27659824 TI - Advanced MR imaging in hemispheric low-grade gliomas before surgery; the indications and limits in the pediatric age. AB - INTRODUCTION: Advanced magnetic resonance imaging (MRI) techniques is an umbrella term that includes diffusion (DWI) and diffusion tensor (DTI), perfusion (PWI), spectroscopy (MRS), and functional (fMRI) imaging. These advanced modalities have improved the imaging of brain tumors and provided valuable additional information for treatment planning. Despite abundant literature on advanced MRI techniques in adult brain tumors, few reports exist for pediatric brain ones, potentially because of technical challenges. REVIEW OF THE LITERATURE: The authors review techniques and clinical applications of DWI, PWI, MRS, and fMRI, in the setting of pediatric hemispheric low-grade gliomas. PERSONAL EXPERIENCE: The authors propose their personal experience to highlight benefits and limits of advanced MR imaging in diagnosis, grading, and presurgical planning of pediatric hemispheric low-grade gliomas. DISCUSSION: Advanced techniques should be used as complementary tools to conventional MRI, and in theory, the combined use of the three techniques should ensure achieving the best results in the diagnosis of hemispheric low-grade glioma and in presurgical planning to maximize tumor resection and preserve brain function. FUTURE PERSPECTIVES: In the setting of pediatric neurooncology, these techniques can be used to distinguish low-grade from high-grade tumor. However, these methods have to be applied on a large scale to understand their real potential and clinical relapse, and further technical development is required to reduce the excessive scan times and other technical limitations. PMID- 27659825 TI - PET and SPECT studies in children with hemispheric low-grade gliomas. AB - Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors. PMID- 27659827 TI - Glioneuronal tumors of cerebral hemisphere in children: correlation of surgical resection with seizure outcomes and tumor recurrences. AB - OBJECT: Glioneuronal tumors are common neoplasms among the cerebral hemisphere during childhood. They consist of several histological types, of which gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) are most common and often present with seizures. A great majority of glioneuronal tumors are benign. However, there are conflict reports regarding postoperative tumor recurrence rates and seizure control. The authors analyzed and compared these tumors for their locations and histology and the tumor and seizure control following resection. METHODS: The authors conducted a retrospective analysis of patients with pediatric glioneuronal tumors in the cerebral hemisphere. All histology reports and neuroimaging are reviewed. Seizure group and non-seizure group were compared with their tumor types and locations. The extent of tumor resections were divided into gross total resection (GTR) and subtotal resection (STR). Postoperative tumor recurrence-free survival (RFS) and seizure-free survival for patients who had the initial surgery done at our institution were calculated using Kaplan-Meier method. RESULTS: There were 90 glioneuronal tumors including 58 GGs, 22 DNTs, 3 papillary glioneuronal tumor, 3 desmoplastic infantile gangliogliomas, 3 anaplastic GGs, and 1 central neurocytoma. Seventy one patients (seizure group) presented with seizures. The temporal lobe is the most common location, 50 % in this series. GTR was attained in 79 patients and STR in 11. All of the patients with GTR had lesionectomy, and only six of them had extended corticectomy or partial lobectomy. Postoperative seizure outcome showed that 64 (90 %) of seizure group had Engel's class I, but five patients subsequently developed recurrent seizures. Patients with DNTs had a higher seizure recurrence rate. Tumor RFS was 87 % at 5 years and 75.5 % at 10 years. There are no significant difference in tumor recurrences between GGs and DNTs (p = 0.876). Comparison between GRT (67) and STR (9) showed that in spite of the better 5-year tumor RFSs among GRT group (94 %) than STR group (66 %), the 10 year RFSs showed no significant difference between GRT and STR groups (p = 0.719). Recurrent seizures are often related to recurrent tumor. CONCLUSION: Lesionectomy alone often provides a high-rate seizure freedom. GGs and DNTs are benign tumor, but recurrences of GGs and DNTs are not uncommon. They may show late recurrences in spite of GTR. These patients need longer follow-up for 10 years. Recurrent seizures are often related to a tumor recurrence. PMID- 27659826 TI - Supratentorial tumors typical of the infantile age: desmoplastic infantile ganglioglioma (DIG) and astrocytoma (DIA). A review. AB - OBJECT: Desmoplastic infantile gangliogliomas (DIGs) and desmoplastic infantile astrocytomas (DIAs) are tumors typical of the infantile age. A large size, with a mixed solid and cystic component, clinical presentation with progressing signs of increased intracranial pressure, a prominent benign desmoplastic structure at histological examination, and a favorable clinical course in the majority of cases are the prominent features of these tumors. The objective of the present paper was to review the pertinent literature on the topic together with our personal experience, with the aim of an updated review of the subject. RESULTS AND CONCLUSIONS: Only 28 papers are present in the literature devoted to DIGs and DIAs, most of them reporting on single cases or small series, with a total of 107 patients aged from 5 days to 48 months with a slight male prevalence. Most of the reported cases refer to supratentorial and hemispheric locations, a few cases involving the hypothalamic region, the posterior fossa, and the spinal cord. The typical MRI appearance is of large mixed solid and cystic tumors with a spontaneous hyperintense T2 appearance of the solid part which also shows a strong contrast enhancement. Mixed ganglionic and astrocytic cells are identifiable in DIGs, whereas DIAs are typically featured by the exclusive presence of glial cells. In both cases, more primitive cells may be observed, which present a higher number of mitoses and these areas can mimic the features of malignant astrocytomas. Surgery represents the treatment of choice; however, radical removal has been reported as possible only in around 30 % of the cases: the low age of the patients together with their low weight and the large size of and the hyper-vascularized structure of the tumors represent the main factors limiting surgery. Pure observation is considered as first choice in children undergoing a partial/subtotal tumor resection, chemotherapic regimens being considered in cases of recurrences after a second look surgery. Long-term prognosis is favorable with mortality being related mostly to the rare midline (i.e., hypothalamic) locations, which beyond the functionally relevant site, tend to have an unusually more aggressive histological behavior. PMID- 27659828 TI - Intra-operative neurophysiological mapping and monitoring during brain tumour surgery in children: an update. AB - INTRODUCTION: Over the past decade, the reluctance to operate in eloquent brain areas has been reconsidered in the light of the advent of new peri-operative functional neuroimaging techniques and new evidence from neuro-oncology. To maximise tumour resection while minimising morbidity should be the goal of brain surgery in children as much as it is in adults, and preservation of brain functions is critical in the light of the increased survival and the expectations in terms of quality of life. DISCUSSION: Intra-operative neurophysiology is the gold standard to localise and preserve brain functions during surgery and is increasingly used in paediatric neurosurgery. Yet, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation, and some technical aspects need to be tailored for its use in children, especially in infants. This paper will review the most recent advances in the field of intra-operative neurophysiology (ION) techniques during brain surgery, focussing on those aspects that are relevant to the paediatric neurosurgery practice. PMID- 27659830 TI - Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: insular lesions. AB - Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult's series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy. PMID- 27659829 TI - Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations. AB - INTRODUCTION: Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. METHODS: In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. RESULTS: This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10 years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. CONCLUSIONS: Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10 years, only few pediatric patients are nonetheless candidates for awake brain surgery. PMID- 27659832 TI - Neurosurgical tools to extend tumor resection in hemispheric low-grade gliomas: conventional and contrast enhanced ultrasonography. AB - PURPOSE: Pediatric low-grade gliomas (LGGs) are the most frequent solid tumor in childhood. Based on an increasing number of literature reports, maximal safe resection is recommended as the first line of treatment whenever possible. However, distinguishing tumor tissue from the surrounding normal brain is often challenging with infiltrating neoplasms, even with the assistance of intraoperative, microscopic and conventional neuronavigation systems. Therefore, any technique that enhances the detection and visualization of LGGs intraoperatively is certainly desirable. METHODS: In this paper, we reviewed the role of intraoperative conventional ultrasound and contrast-enhanced ultrasound (CEUS) as a tool for extending tumor resection in LGGs. Moreover, our experience with this technology is reported and discussed. RESULTS: Both B-mode and CEUS are helpful in highlighting LGGs, detecting tumor margins and providing additional information such as vascularization, thus improving the safety of a more radical resection. CONCLUSIONS: Although the full potentialities of the method are yet to be explored, intraoperative ultrasound is a promising tool in oncologic surgery and LGG surgery. PMID- 27659831 TI - Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions. AB - BACKGROUND: Tumors with epicenter in the thalamus occur in about 4 % of pediatric brain tumors. The histological diagnosis is mainly gliomas. Among them, low-grade glioma (LGG) constituted of a significant entity of the tumors (Cuccia et al., Childs Nerv Syst 13:514-521, 1997; Puget et al., J Neurosurg 106:354-362, 2007; Bernstein et al., J Neurosurg 61:649-656, 1984; Bilginer et al., Childs Nerv Syst 30:1493-1498, 2014). Since Kelly's report in 1989, >90 % resection of thalamic tumors were achieved in reported series (Ozek and Ture, Childs Nerv Syst 18:450 6, 2002; Villarejo et al., Childs Nerv Syst 10:111-114, 1994; Moshel et al., Neurosurgery 61:66-75, 2007; Albright, J Neurosurg 100(5 Suppl Pediatrics): 468 472, 2004; Kelly, Neurosurgery 25:185-195, 1989; Drake et al., Neurosurgery 29: 27-33, 1991). MATERIALS AND METHODS: Sixty-nine cases of thalamic tumors in children were retrospectively reviewed. There were 25 cases of LGGs. We analyzed our experience and correlated it with reported series. RESULTS: Summing up of 4 reported series and the present series, there were 267 cases of thalamic tumors in children. Among these tumors, 107 (40.1 %) were LGGs and 91 (34.1 %) were low grade astrocytomas (LGAs). In the present series, all of the 25 LGGs were LGAs that consisted of 11 pilocytic astrocytomas (PAs) and 14 diffuse astrocytomas (DAs). Six cases received biopsy sampling only. The remaining 19 cases received different degrees of surgical resection via several approaches. Radical (>90 %) resection was achieved better in PAs comparing with DAs. There was no operative mortality. Two patients had increased neurological deficits. In a mean follow-up period of 11.9 years, three patients died of tumor progression and one patient died of anaplastic change. The 5- and 10-year overall survival (OS) was 87.1 and 87.1 %, respectively. CONCLUSION: Thalamic LGGs are mainly LGAs and are indolent. The rate of >90 % resection was relatively low in the present series. By applying contemporary diagnostic MRI studies, surgical facilities, and appropriate approaches in selective cases, we may try maximum neuroprotective radical (>90 %) resection. PMID- 27659833 TI - Neurosurgical tools to extend tumor resection in pediatric hemispheric low-grade gliomas: iMRI. AB - INTRODUCTION: The treatment of low-grade gliomas (LGGs) in pediatric age is still controversial. However, most authors report longer life expectancy in case of completely removed cerebral gliomas. Intraoperative magnetic resonance imaging (iMRI) is increasingly utilized in the surgical management of intra-axial tumor in adults following the demonstration of its effectiveness. In this article, we analyze the management of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population. METHODS: We performed review of the literature regarding the treatment of LGG using iMRI focusing on its impact on resection rate and its limits in the pediatric population. Some exemplary cases are also described. RESULTS: Intraoperative MRI allowed extension of tumor resection after the depiction of residual tumor at the intraoperative imaging control from 21 to 52 % of the cases in the published series. Moreover, the early reoperation rate was significantly lower when compared with the population treated without this tool (0 % vs 7-14 %). Some technical difficulties have been described in literature regarding the use of iMRI in the pediatric population especially for positioning due to the structure of the headrest coil designed for adult patients. CONCLUSION: The analysis of the literature and our own experience with iMRI in children indicates significant advantages in the resection of LGG offered by the technique. All these advantages are obtained without elongation of the surgical times or increased risk for complications, namely infection. The main limit for a wider diffusion of iMRI for the pediatric neurosurgical center is the cost required, for acquisition of the system, especially for high-field magnet, and the environmental and organizational changes necessary for its use. PMID- 27659834 TI - Epilepsy surgery for pediatric low-grade gliomas of the cerebral hemispheres: neurosurgical considerations and outcomes. AB - INTRODUCTION: Pediatric low-grade tumors are found in roughly 1-3 % of patients with childhood epilepsy; seizures associated with these tumors are often medically refractory and often present a significant morbidity, greater than the presence of the tumor itself. DISCUSSION: The unique morbidity of the seizures often requires an epilepsy surgical approach over a standard oncologic resection to achieve a reduction in morbidity for the child. Multiple quality-of-life studies have shown that unless a patient is seizure-free, they remain disabled throughout their life; the best way to achieve this in our patient population is with a multidisciplinary team approach with treatment goals focusing primarily on the epilepsy. CONCLUSION: In those patients treated with gross total resection, roughly 80 % will have an Engel class I outcome and 90 % will achieve some reduction in seizure frequency with a significant improvement in quality of life. PMID- 27659835 TI - Preoperative neurocognitive evaluation as a predictor of brain tumor grading in pediatric patients with supratentorial hemispheric tumors. AB - OBJECTIVE: The objective of the present study was to retrospectively evaluate the relationship between tumor grading and a selective evaluation of neurocognitive and behavioral functions in children with supratentorial hemispheric brain tumors. METHODS: Children admitted with a diagnosis of supratentorial hemispheric tumors involving the cerebral hemispheres or the thalamus at the Pediatric Neurosurgery Unit of the Catholic University of Rome between January 2008 and January 2014 were considered for the present study. Exclusion criteria were represented by age less than 2 years, severe neurological deficits, seizures, and a metastatic disease. A selective neurocognitive and behavioral workout was used for children aged less and more than 5 years. RESULTS: Global cognitive functions as well as selective neurocognitive and behavioral profiles were found to be significantly worse in children with low-grade tumors, compared with those affected by higher-grades histotypes. Frontal locations for cortical tumors and thalamic lesions were significantly related with worse results, with a clear contribution of dominant vs. nondominant hemisphere involvement and an age higher than 5 years. CONCLUSIONS: Preoperative global and selective neurocognitive evaluation might contribute to the prediction of the tumor aggressiveness. Due to a longer clinical history, more benign tumors more frequently arrive to the diagnosis with a neurocognitive compromise in spite of an apparently mild presence of neurological symptoms and signs. PMID- 27659838 TI - 44th Annual Meeting of International Society for Pediatric Neurosurgery, Kobe, Japan, Oct 23-27, 2016. PMID- 27659836 TI - Conventional chemotherapy and perspectives for molecular-based oncological treatment in pediatric hemispheric low-grade gliomas. AB - INTRODUCTION: Pediatric low-grade gliomas (PLGG) are the most common primary central nervous system tumor in children. Patients in whom gross total resection can be achieved have an excellent overall (OS) and event-free survival (EFS) and do not require adjuvant therapy. However, children with unresectable tumors often experience multiple progressions and require additional treatment. CONVENTIONAL CHEMOTHERAPY: Radiotherapy results in long-term tumor control, but it is associated with significant toxicity, making chemotherapy the preferred therapeutic option. Several chemotherapy combinations have been found to be successful in PLGG, but 5-year EFS has been below 60 % with most of them. MOLECULAR-BASED TREATMENT: Recent molecular advances have led to a better understanding of the molecular pathways involved in the biology of LGG, allowing the development of promising tumor-specific, molecularly targeted therapies. PMID- 27659837 TI - MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives. AB - BACKGROUND: Pediatric low-grade gliomas (LGGs) account for approximately half of all pediatric central nervous system tumors. The low-grade gliomas' first line of treatment is gross total resection. However, when gross total resection is not possible, options for adjuvant therapy are limited. MRI-guided laser ablation (magnetic resonance-guided laser interstitial thermal therapy (MRgLITT)) offers a new option for treatment in selected cases. We present a description of the current MRgLITT technology and an exemplary case-series review of our experience in its use in LGGs. CASE DESCRIPTION: A 19-month-old male was referred to the pediatric neurosurgery clinic with an incidental left temporal lesion discovered on a prenatal ultrasound. An MRI of the brain revealed a diffuse mesial temporal lesion. Electroencephalogram (EEG) showed generalized activity arising from the lesion. The patient underwent a navigation-guided biopsy then, two bolts were secured to the skull, and laser ablation was performed with intraoperative MR guidance. Pathology was consistent with ganglioglioma. Follow-up images 13 months after ablation showed a significant volumetric reduction in size of the tumor. DISCUSSION: It is important to achieve maximal resection of low-grade gliomas in children, lessening the need for adjuvant chemotherapy and radiotherapy, while minimizing the length of hospital stay and disruption to the child's life. Of our nine LGGs patients treated with this technology, six had undergone previous surgery and MRgLITT proved itself to be a safe surgical treatment option to achieve further cytoreduction. While most of the cases are pilocytic astrocytomas, the location of the tumors was surgically challenging. Eight of the nine cases required a single trajectory-laser-while our case example requires two lasers. Only a case of a midbrain-thalamic tumor presented a post-ablation significant brain edema as perioperative complication [1]. Eight of the nine tumors did not require any coadjuvant therapy or further surgical treatment to date. CONCLUSION: MRIgLITT is a successful option for treatment for selected de novo or recurrent low-grade gliomas in children. It can be combined with other therapies offering the advantages of a minimally invasive procedure. LITT may be added to the current pediatric neuro-oncology protocols, but larger prospective series are needed to show the effectiveness of LITT and to standardize indications and protocols. PMID- 27659839 TI - Detection of clonal heterogeneity and targetable mutations in myeloid sarcoma by high-throughput sequencing. PMID- 27659840 TI - The effects of cognitive and behavioural therapies for anxiety disorders on depression: a meta-analysis. AB - BACKGROUND: The effects of cognitive behavioural therapy of anxiety disorders on depression has been examined in previous meta-analyses, suggesting that these treatments have considerable effects on depression. In the current meta-analysis we examined whether the effects of treatments of anxiety disorders on depression differ across generalized anxiety disorder (GAD), social anxiety disorder (SAD) and panic disorder (PD). We also compared the effects of these treatments with the effects of cognitive and behavioural therapies of major depression (MDD). METHOD: We searched PubMed, PsycINFO, EMBASE and the Cochrane database, and included 47 trials on anxiety disorders and 34 trials on MDD. RESULTS: Baseline depression severity was somewhat lower in anxiety disorders than in MDD, but still mild to moderate in most studies. Baseline severity differed across the three anxiety disorders. The effect sizes found for treatment of the anxiety disorders ranged from g = 0.47 for PD, g = 0.68 for GAD and g = 0.69 for SAD. Differences between these effect sizes and those found in the treatment of MDD (g = 0.81) were not significant in most analyses and we found few indications that the effects differed across anxiety disorders. We did find that within-group effect sizes resulted in significantly (p < 0.001) larger effect sizes for depression (g = 1.50) than anxiety disorders (g = 0.73-0.91). Risk of bias was considerable in the majority of studies. CONCLUSIONS: Patients participating in trials of cognitive behavioural therapy for anxiety disorders have high levels of depression. These treatments have considerable effects on depression, and these effects are comparable to those of treatment of primary MDD. PMID- 27659841 TI - Neuroprogression and illness trajectories in bipolar disorder. AB - INTRODUCTION: The longitudinal course of bipolar disorder is highly variable, and a subset of patients seems to present a progressive course associated with brain changes and functional impairment. Areas covered: We discuss the theory of neuroprogression in bipolar disorder. This concept considers the systemic stress response that occurs within mood episodes and late-stage deficits in functioning and cognition as well as neuroanatomic changes. We also discuss treatment refractoriness that may take place in some cases of bipolar disorder. We searched PubMed for articles published in any language up to June 4th, 2016. We found 315 abstracts and included 87 studies in our review. Expert commentary: We are of the opinion that the use of specific pharmacological strategies and functional remediation may be potentially useful in bipolar patients at late-stages. New analytic approaches using multimodal data hold the potential to help in identifying signatures of subgroups of patients who will develop a neuroprogressive course. PMID- 27659842 TI - Characterization of Lr75: a partial, broad-spectrum leaf rust resistance gene in wheat. AB - KEY MESSAGE: Here, we describe a strategy to improve broad-spectrum leaf rust resistance by marker-assisted combination of two partial resistance genes. One of them represents a novel partial adult plant resistance gene, named Lr75. Leaf rust caused by the fungal pathogen Puccinia triticina is a damaging disease of wheat (Triticum aestivum L.). The combination of several, additively-acting partial disease resistance genes has been proposed as a suitable strategy to breed wheat cultivars with high levels of durable field resistance. The Swiss winter wheat cultivar 'Forno' continues to show near-immunity to leaf rust since its release in the 1980s. This resistance is conferred by the presence of at least six quantitative trait loci (QTL), one of which is associated with the morphological trait leaf tip necrosis. Here, we used a marker-informed strategy to introgress two 'Forno' QTLs into the leaf rust-susceptible Swiss winter wheat cultivar 'Arina'. The resulting backcross line 'ArinaLrFor' showed markedly increased leaf rust resistance in multiple locations over several years. One of the introgressed QTLs, QLr.sfr-1BS, is located on chromosome 1BS. We developed chromosome 1B-specific microsatellite markers by exploiting the Illumina survey sequences of wheat cv. 'Chinese Spring' and mapped QLr.sfr-1BS to a 4.3 cM interval flanked by the SSR markers gwm604 and swm271. QLr.sfr-1BS does not share a genetic location with any of the described leaf rust resistance genes present on chromosome 1B. Therefore, QLr.sfr-1BS is novel and was designated as Lr75. We conclude that marker-assisted combination of partial resistance genes is a feasible strategy to increase broad-spectrum leaf rust resistance. The identification of Lr75 adds a novel and highly useful gene to the small set of known partial, adult plant leaf rust resistance genes. PMID- 27659844 TI - Role, timing and technique of radiotherapy in pediatric pleuropulmonary synovial sarcoma. AB - The management of pediatric thoracic synovial sarcoma remains a matter of debate in clinical oncology, especially as regard to the local control of the disease. Surgery remains the gold standard, while the role and timing of radiotherapy is still controversial. We report a 14-year-old male, who has not received proper treatment at the time of diagnosis and initial management. Intensity-modulated irradiation was performed only at relapse, as a salvage treatment and, at 10 month follow-up, the young patient was free from relapse, without significant acute and subacute toxicity. We discuss the role and timing of radiotherapy in thoracic synovial sarcoma, a disease in which the need to increase local control should be placed in the foreground. PMID- 27659843 TI - Development of an integrated linkage map of einkorn wheat and its application for QTL mapping and genome sequence anchoring. AB - KEY MESSAGE: An integrated genetic map was constructed for einkorn wheat A genome and provided valuable information for QTL mapping and genome sequence anchoring. Wheat is one of the most widely grown food grain crops in the world. The construction of a genetic map is a key step to organize biologically or agronomically important traits along the chromosomes. In the present study, an integrated linkage map of einkorn wheat was developed using 109 recombinant inbred lines (RILs) derived from an inter sub-specific cross, KT1-1 (T. monococcum ssp. boeoticum) * KT3-5 (T. monococcum ssp. monococcum). The map contains 926 molecular markers assigned to seven linkage groups, and covers 1,377 cM with an average marker interval of 1.5 cM. A quantitative trait locus (QTL) analysis of five agronomic traits identified 16 stable QTL on all seven chromosomes, except 6A. The total phenotypic variance explained by these stable QTL using multiple regressions varied across environments from 8.8 to 87.1 % for days to heading, 24.4-63.0 % for spike length, 48.2-79.6 % for spikelet number per spike, 13.1-48.1 % for plant architecture, and 12.2-26.5 % for plant height, revealing that much of the RIL phenotypic variation had been genetically dissected. Co-localizations of closely linked QTL for different traits were frequently observed, especially on 3A and 7A. The QTL on 3A, 5A and 7A were closely associated with Eps-A m 3, Vrn1 and Vrn3 loci, respectively. Furthermore, this genetic map facilitated the anchoring of 237 T. urartu scaffolds onto seven chromosomes with a physical length of 26.15 Mb. This map and the QTL data provide valuable genetic information to dissect important agronomic and developmental traits in diploid wheat and contribute to the genetic ordering of the genome assembly. PMID- 27659846 TI - 15th Annual Meeting of the Safety Pharmacology Society: Focus on traditional sensory systems. AB - INTRODUCTION: This report summarizes and comments key talks on the five traditional senses (ear, vestibular system, vision, taste, olfaction, and touch) which were delivered during the 2015 Annual Meeting of the Safety Pharmacology (SP) Society. AREAS COVERED: The functional observational battery (FOB) can detect major candidate drug liabilities only on ear, touch and vision. Anatomy, physiology, pharmacology, and pathology notions on each sensory system introduce speaker talks. Techniques for evaluating drug effects on hearing functions are reviewed. Nonclinical approaches to assess vestibular toxicity leading to balance deficits are presented. Retinal explants studied with multielectrode arrays allow the identification of drug liability sites on the retina. Routinely performed Safety Pharmacology assays are not powered to address candidate drug-induced disturbances on taste and smell. This weakness needs correction since unintended pharmacological impairment of these sensorial functions may have serious health consequences. Neuropathy produced by chemotherapeutic agents may cause multiple sensorial perception distortions. CONCLUSIONS: Safety Pharmacology studies should ensure the safety of any candidate drug on the five sensorial systems. PMID- 27659845 TI - Acute and subacute toxicity of an ethanolic extract of Melandrii Herba in Crl:CD sprague dawley rats and cytotoxicity of the extract in vitro. AB - BACKGROUND: Melandrii Herba, a medicinal plant, has been used in Korea for treatment of bacterial and fungal infection. However, the safety and toxicity of Melandrii Herba have not yet been established. Therefore, we investigated the acute and subacute toxicity of an ethanolic extract of Melandrii Herba (MHEE) in Crl:CD Sprague Dawley rats and cytotoxicity of MHEE in vitro. METHODS: To study acute toxicity, rats were treated with MHEE at single doses of 0, 500, 1000, and 2000 mg/kg administered by oral gavage, and body weight, clinical signs, and mortality were observed after dosing. To study subacute toxicity, rats were treated with MHEE at doses of 0, 500, 1000, and 2000 mg/kg administered once a day by gavage for 4 weeks. We measured clinical signs, mortality, gross pathological findings, body and organ weights, food consumption, serum biochemistry, and conducted hematology and urinalysis. The cytotoxicity of MHEE was assayed by measuring the viability of prostate cell lines including normal prostate stromal WPMY-1, normal prostate epithelial RWPE-1, and benign prostatic hyperplasia epithelial BPH-1 cells at various concentrations of MHEE in vitro. RESULTS: Single oral doses of MHEE caused no significant difference in rat clinical signs, mortality, or body weight. The lethal dose of MHEE was considered to be >2000 mg/kg. Daily oral doses of MHEE for 4 weeks did not result in any significant changes in rat mortality, gross pathological findings, relative organ weights, food consumption, hematology, serum biochemistry, or urinalysis. At MHEE >1000 mg/kg/day, salivation was increased in both male and female rats. However, the salivation caused by the MHEE treatment was not accompanied by pathological changes in body weight or gross pathological findings, and we considered the salivation as a minor symptom. Therefore, no adverse effects were seen at 2000 mg/kg/day or less. MHEE showed no cytotoxic effects on either normal prostate or benign prostatic hyperplasia cell lines. CONCLUSIONS: Administration of MHEE in Crl:CD Spradgue Dawley rats is nontoxic and is safe for at least a month. PMID- 27659847 TI - Bordetella bronchiseptica antigen enhances the production of Mycoplasma hyopneumoniae antigen-specific immunoglobulin G in mice. AB - We previously demonstrated that Bordetella (B.) bronchiseptica antigen (Ag) showed high immunostimulatory effects on mouse bone marrow cells (BMs) while Mycoplasma (M.) hyopneumoniae Ag showed low effects. The focus of this study was to determine if B. bronchiseptica Ag can enhance the M. hyopneumoniae Ag-specific immune response and whether the host's immune system can recognize both Ags. MTT assay results revealed that each or both Ags did not significantly change BM metabolic activity. Flow cytometry analysis using carboxyfluorescein succinimidyl ester showed that B. bronchiseptica Ag can promote the division of BMs. In cytokine and nitric oxide (NO) assays, B. bronchiseptica Ag boosted production of tumor necrosis factor-alpha in M. hyopneumoniae Ag-treated BMs, and combined treatment with both Ags elevated the level of NO in BMs compared to that from treatment of M. hyopneumoniae Ag alone. Immunoglobulin (Ig)G enzyme-linked immunosorbent assay using the sera of Ag-injected mice clearly indicated that B. bronchiseptica Ag can increase the production of M. hyopneumoniae Ag-specific IgG. This study provided information valuable in the development of M. hyopneumoniae vaccines and showed that B. bronchiseptica Ag can be used both as a vaccine adjuvant and as a vaccine Ag. PMID- 27659848 TI - Radiological assessment of the PRF/BMSC efficacy in the treatment of aseptic nonunions: A retrospective study on 90 subjects. AB - BACKGROUND: Nonunion is a major orthopaedic concern because of treatment difficulty, high costs and devastating effects on the patients' life quality. Therefore, there is interest in the use of bone substitutes and cell-based strategies to augment fracture repair. We aimed to verify if Platelet Rich Fibrin (PRF) added with bone marrow stromal cells (BMSC) was able to improve the reparative process in the aseptic nonunion, and to establish whether it was worthwhile with atrophic nonunion. The primary outcome was radiological union. As secondary endpoint, the healing time was assessed, and the radiological consolidation grade at each follow-up. METHODS: We identified 113 subjects with tibia or femur nonunion and retrospectively created two groups. Group A was constituted by 56 subjects who underwent the standard procedure, i.e. Judet decortication with/out internal fixation devices, and opposite cortical homoplastic stick. In 57 patients, the standard procedure was modified by adding PRF and BMSC carried by homologous lyophilised bone chips (group B). The same surgeon performed all the operations. To our knowledge, no data are reported in the literature about such application. Since a "gold standard" for healing quantification does not exist, a new scoring radiological system was applied, at 1.5, 3, 6, 12 and 24 months after treatment. RESULTS: At the final 24-month follow-up, the radiological union percentage was 94,12 in group B and 95,12% in group A. A decreased healing time was demonstrated in the presence of PRF/BMSC in comparison with the standard procedure. When we compared the radiological scores at each follow-up, we found that the PRF/BMSC combination significantly improved the consolidation grade at 1.5-, 3- and 6-month follow-up in femurs and at 1.5 month follow-up in tibiae. Furthermore, an improved consolidation grade was demonstrated in the atrophic subjects treated with adjuvants compared to atrophic patients treated with the standard procedure at 1.5-month follow-up. CONCLUSIONS: This study supports the concept that the use of PRF/BMSC, during the standard procedure, is effective in shortening nonunion healing time. It could allow an early mobilization of patients, minimizing suffering, and could be an effective tool to reduce the health-care costs resulting from this issue. LEVEL OF EVIDENCE: Therapeutic level III. PMID- 27659849 TI - Factors associated with pain intensity and physical limitations after lateral ankle sprains. AB - BACKGROUND: Swelling, tenderness, and ecchymosis don't correlate with time to functional recovery in patients with a lateral ankle sprain. It is established that psychosocial factors such as symptoms of depression and low pain self efficacy correlate with pain intensity and magnitude of limitations in patients with musculoskeletal disorders. OBJECTIVE: We studied the correlation between pain self-efficacy or symptoms of depression and (1) ankle specific limitations and (2) pain intensity in patients with a lateral ankle sprain. Further we explored the correlation between estimation of sprain severity (grade) and (3) pain intensity or magnitude of ankle specific limitations. DESIGN: Eighty-four patients with a lateral ankle sprain prospectively completed the Pain Self Efficacy Questionnaire, the Olerud Molander Ankle Score, Ordinal scale of Pain and the Patient Health Questionnaire-2 at enrollment and the Olerud Molander Ankle Score and the Ordinal scale of Pain three weeks after the injury. Factors associated with higher ankle specific limitations and symptoms were investigated in bivariable and multivariable analysis. RESULTS: When accounting for confounding factors, greater self-efficacy (p=0.01) and older age (p<0.01) were significantly associated with greater ankle specific symptoms and limitations three weeks after the injury and explained 22% of the variability in ankle specific limitations and symptoms. There was no correlation between the grade of the sprain and pain intensity or ankle specific limitations or symptoms. CONCLUSIONS: Psychosocial factors (adaptiveness in response to pain in particular) explain more of the variation in symptoms and limitations after ankle sprain than the degree of pathophysiology. The influence of adaptive illness descriptions and recovery strategies based on methods for improving self-efficacy (i.e. cognitive behavioral therapy) might enhance and speed recovery from ankle injuries and merit additional investigation. LEVEL OF EVIDENCE: Level 2 prospective cohort study. PMID- 27659850 TI - A biomechanical study of proximal tibia bone grafting through the lateral approach. AB - BACKGROUND: Autologous bone graft remains the gold standard source of bone graft. Iliac crest has traditionally been the most popular source for autologous bone graft. However, iliac crest bone graft harvesting is associated with high donor site morbidity. Bone graft harvesting from the proximal tibia has shown great potential with reported low complication rates. However, there is a paucity of biomechanical studies concerning the safety as well as yield of proximal bone graft harvesting. PURPOSE: This biomechanical study was designed to investigate (1) the stability of the harvested proximal tibial during physiological loading, and (2) the maximum size of the cortical window that can be safely created and (3) volume of accessible bone graft. METHODS: Bone grafts were harvested from eleven cadaveric tibiae using a circular cortical window along the lateral proximal tibia. These harvested proximal tibiae were then loaded under physiological conditions (mean 2320N, range 1650-3120N) using a customized test fixture. Strain rosettes were mounted at 7 locations in the harvested proximal tibia to record the changes in strain at the harvested proximal tibia. The change in strain with increasing cortical window size (10-25mm diameter) was also studied. Bone principal strains as well as volume of bone harvested were recorded. RESULTS: A repeated measures ANOVA was used to analyze the change in bone strains with the cortical window size. Statistically significant (p<0.05) increases in bone strains at the anterior and medial aspects of the tibia were observed with increasing size of osteotomies (-328.85MUepsilon, SD=232.21 to 964.78MUepsilon, SD=535.89 and 361.64MUepsilon, SD=229.90 to -486.08MUepsilon, SD=270.40 respectively), and marginally significant changes in strain at the lateral and posterior aspects. None of the tibiae failed under normal walking loads even with increasing osteotomies size of 10-25 mm diameter. A smaller osteotomy of 10mm diameter yielded an average volume of 7.15ml of compressed bone graft, while a larger osteotomy of 25mm diameter yielded on average an additional 3.64ml of bone graft. Bone grafting of the proximal tibia through the lateral approach with a circular osteotomy is a feasible option even with osteotomies of 25mm diameter. Even though increased bone strains were observed, the strains did not exceed the yield strain of cortical bone when loaded under normal walking conditions. The quantity of bone harvested from the proximal tibia is comparable to that harvested from the iliac crest. CONCLUSIONS: This biomechanical study demonstrated the stability of the harvested proximal tibia under conditions of full weight bearing ambulation. It has also refined the technique of proximal bone graft harvesting by determining the maximum size of the cortical window. The findings of this study add to the overall understanding of proximal tibial bone graft harvesting, providing objective data regarding stability as well as yield. This information would be useful during selection of source of autologous bone graft. PMID- 27659851 TI - Fluid-Attenuated Inversion Recovery Vascular Hyperintensity Topography, Novel Imaging Marker for Revascularization in Middle Cerebral Artery Occlusion. AB - BACKGROUND AND PURPOSE: In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment. METHODS: We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH ASPECTS topography. RESULTS: Among 101 patients who met inclusion criteria for the study, mean age was 66.2+/-17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019). CONCLUSIONS: Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion. PMID- 27659852 TI - Nursing's Role in Successful Transitions Across Settings. PMID- 27659853 TI - Long-Term Clinical Impact of Vascular Brain Lesions on Magnetic Resonance Imaging in Older Adults in the Population. AB - BACKGROUND AND PURPOSE: White matter hyperintensity (WMH) volume and covert brain infarcts are highly prevalent in older adults and are often asymptomatic. We compared the impact of WMH volume and brain infarcts on risk of clinical stroke and dementia in older adults in the population. METHODS: Participants were 1677 individuals aged >=65 years from the 3-City Dijon study, who were free of stroke and dementia at baseline, followed-up for <=12 years. RESULTS: Both lesion types were comparably associated with an increased risk of stroke (adjusted hazard ratio, 1.72; 95% confidence interval, 1.24-2.40 for WMH volume and hazard ratio, 2.15; 95% confidence interval, 1.18-3.93 for brain infarcts), but only WMH volume was associated with an increased risk of dementia (hazard ratio, 1.41; 95% confidence interval, 1.09-1.83). CONCLUSIONS: The differential impact of WMH and brain infarcts on clinical stroke and dementia suggests relatively different prognostic value of the 2 lesions. WMHs may represent a particularly pertinent magnetic resonance imaging intermediate marker that can be utilized in optimizing prevention strategies for both stroke and dementia in primary care and in trials. PMID- 27659854 TI - Impact of Membrane Drug Transporters on Resistance to Small-Molecule Tyrosine Kinase Inhibitors. AB - Small-molecule inhibitors of tyrosine kinases (TKIs) are the mainstay of treatment for many malignancies and represent novel treatment options for other diseases such as idiopathic pulmonary fibrosis. Twenty-five TKIs are currently FDA-approved and >130 are being evaluated in clinical trials. Increasing evidence suggests that drug exposure of TKIs may significantly contribute to drug resistance, independently from somatic variation of TKI target genes. Membrane transport proteins may limit the amount of TKI reaching the target cells. This review highlights current knowledge on the basic and clinical pharmacology of membrane transporters involved in TKI disposition and their contribution to drug efficacy and adverse drug effects. In addition to non-genetic and epigenetic factors, genetic variants, particularly rare ones, in transporter genes are promising novel factors to explain interindividual variability in the response to TKI therapy. PMID- 27659855 TI - Invalidation of Atorvastatin Patent Highlights Complex Chinese Patent Law. AB - Pfizer's atorvastatin (Lipitor) is a blockbuster drug for the treatment of cardiovascular diseases. In China, a critical polymorph patent of this drug has been recently invalidated by the Supreme People's Court for insufficiency of disclosure. Here, we discuss the particularities in patent litigation in China worth attention from the community. PMID- 27659856 TI - New Treatments for Type 2 Diabetes Mellitus and Cardiovascular Disease. The Revolution Has Begun. PMID- 27659857 TI - Recurrent Pericarditis as the Presenting Form of Adult Still's Disease. PMID- 27659858 TI - Acute Clinical Presentation of Pseudoaneurysm and Aortopulmonary Fistula as a Very Late Complication of Aortic Coarctation Patch Repair. PMID- 27659859 TI - Epidemiology of primary rubella infection in the Central African Republic: data from measles surveillance, 2007-2014. AB - BACKGROUND: Although rubella is generally considered a benign childhood disease, infection of a pregnant woman can cause foetal congenital rubella syndrome, which results in embryo-foetal disease and malformations. The syndrome is still a public health problem in developing countries where the vaccine has not yet been introduced, such as the Central African Republic (CAR). The aim of the study reported here was to define the epidemiology of primary rubella infection, in order to determine its effect on morbidity rates in the country. METHODS: Data derived from epidemiological surveillance of measles and rubella were analysed retrospectively between 1 January 2007 and 31 December 2014. The database includes cases of suspected measles, according to the WHO clinical case definition. In this algorithm, samples that are negative or doubtful by ELISA for measles (presence of immunoglobulin M) are tested in another ELISA for detection of rubella-specific IgM. Descriptive analyses were conducted for socio demographic characteristics, including age, sex and health region, for patients tested for rubella. RESULTS: Of the sera tested for rubella, 30.2 % (425/1409) were positive, 62.3 % (878/1409) were negative, and 7.5 % (106/1409) were doubtful. Among the 425 positive cases, 213 (50.1 %) were female and 212 (40.9 %) were male with a sex ratio of 1.03. The mean age was 8 years (range, 6-37 years). The highest prevalence (47.3 %; 116/425) was seen in 2007 and the lowest (8.9 %; 11/425) in 2012. Primary infections were always more frequent during the first 3 months of the year, with a peak at the same time, between January and February which is the hottest period of the year in the CAR. In both sexes, rubella IgM was rarely found before the age of 1 year (0.5 %; 2/425). The highest rate (43.5 %; 185/425) was observed at ages 5-9 years; however, at least 8 % (18/213) of girls aged 15 or more had primary infections. CONCLUSIONS: Sentinel sites for surveillance of congenital rubella syndrome are urgently needed, and introduction of vaccination against rubella in the Expanded Programme of Immunization should be considered, to ensure immunization of girls of reproductive age. PMID- 27659860 TI - Alginate nanoparticles protect ferrous from oxidation: Potential iron delivery system. AB - A novel, efficient delivery system for iron (Fe2+) was developed using the alginate biopolymer. Iron loaded alginate nanoparticles were synthesized by a controlled ionic gelation method and was characterized with respect to particle size, zeta potential, morphology and encapsulation efficiency. Successful loading was confirmed with Fourier Transform Infrared spectroscopy and Thermogravimetric Analysis. Electron energy loss spectroscopy study corroborated the loading of ferrous into the alginate nanoparticles. Iron encapsulation (70%) was optimized at 0.06% Fe (w/v) leading to the formation of iron loaded alginate nanoparticles with a size range of 15-30nm and with a negative zeta potential (-38mV). The in vitro release studies showed a prolonged release profile for 96h. Release of iron was around 65-70% at pH of 6 and 7.4 whereas it was less than 20% at pH 2.The initial burst release upto 8h followed zero order kinetics at all three pH values. All the release profiles beyond 8h best fitted the Korsmeyer-Peppas model of diffusion. Non Fickian diffusion was observed at pH 6 and 7.4 while at pH 2 Fickian diffusion was observed. PMID- 27659861 TI - Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier. AB - Although chitosan nanoparticles (CNs) became a promising tool for several biological and medical applications owing to their inherent biocompatibility and biodegradability features, studies regarding their effects on cytotoxic and cytostatic properties still remain insufficient. Therefore, in the present study, we decided to perform comprehensive analysis of the interactions between CNs pKindling-Red-Mito (pDNA) and different cell line models derived from blood system and human solid tissues cancers. The resulting CNs-pDNA was investigated in terms of their cellular uptake, transfection efficiency, and physico-chemical, cytotoxic and cytostatic properties. The nanoparticles showed high encapsulation efficiency and physical stability for various formulations even after two days time period. Moreover, high gene expression levels were observed after 96h of transfection. CNs-pDNA treatment, despite the absence of oxidative stress induction, caused cell cycle arrest in G0/G1 phase and as a consequence led to premature senescence which turned out to be both p21-dependent and p21 independent. Also, observed DNMT2 upregulation may suggest the activation of different pathways protecting from the results of CNs-mediated stress. In conclusion, treatment of different cell lines with CNs-pDNA showed that their biocompatibility was limited and the effects were cell type-dependent. PMID- 27659862 TI - Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus. AB - Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response. PMID- 27659863 TI - Biophysical evaluation of hybrid Fc fusion protein of hGH to achieve basal buffer system. AB - A newly developed hybrid Fc (hyFc) is a non-immunogenic and non-cytolytic Fc with intact Ig structure derived from human IgD and IgG4. It is fused with the human growth hormone (GXD-9) and was evaluated by various biophysical techniques. Two thermal transitions were evident by DSC, reflecting the unfolding of IgG4 and the conjugated protein. The highest Tm of the initial GXD-9 was 68.17 degrees C and the Tm of the two domains were around 66 degrees C and 70 degrees C. Although Tm increased with decreasing concentration, which reflects increasing conformational stability, aggregation issues were still observed by DLS. This might be caused by decreasing or low zeta potential due to a highly complex structure. The protein was dialyzed to various pH (6.2-8.2) values to enhance conformational stability and to overcome aggregation issues. The results of CD spectroscopy were correlated with DSC measurements to evaluate its conformational stability. Changes in secondary structural contents were similar as determined by DSC and DLS. In conclusion, GXD-9 was found to be most stable at pH 7.0. The investigation of the biophysical stability of a hyFc-fusion protein has demonstrated a positive feasibility of developing more stable formulations to facilitate the initial drug development process for further clinical trials. PMID- 27659864 TI - Shortage of healthcare professionals in China. PMID- 27659865 TI - Preeclampsia; short and long-term consequences for mother and neonate. AB - Preeclampsia is a common pregnancy specific disease, that presents with hypertension and a variety of organ failures, including malfunction of kidneys, liver and lungs. At present, the only definitive treatment of preeclampsia is end the pregnancy and deliver the neonate and placenta. For women with mild preeclampsia in the preterm phase of pregnancy, expectant management is generally indicated to improve fetal maturity, often requiring maternal medical treatment. Last decades, more evidence is available that the underlying mechanism of preeclampsia, endothelial disease, is not limited to pregnancy but increases cardiovascular risk in later life. In this review, we present the most recent insight in preeclampsia with focus on impact on the fetus, short and long-term outcome of offspring's, and long-term outcome of women with a history of preeclampsia. PMID- 27659866 TI - The effect of recycled plastics and cooking oil on coke quality. AB - This study assessed the effects of adding plastics and waste vegetable oil on the quality of coke in the coking process, on a pilot scale. A typical composition of the main plastics found in municipal solid waste was prepared using 33% HDPE, 5% LDPE, 10% PP, 21% PET, 24.8% PS, 5.2% PVC, 1% cellulose and also a 0.5% waste vegetable oil was added. The wastes were added to the coal blends in the proportions of 1%, 2% and 3% for plastics and 0.5% for vegetable oil. Two types of experiments were performed. The first was carried out in a hearth heating furnace (HHF) at temperatures of up to 900 degrees C for a 7 h period. The second was a box test, which consists of heating coal blends in 18L cans using a pilot coking oven, for approximately 20 h at temperatures between 1050 and 1100 degrees C. The quality parameters used for the assessment were the CSR (coke strength after reaction), CRI (coke reactivity index), ash, volatile matter and sulfur in order to identify the effect of plastic and vegetable oil on coke quality. Results for CSR in the HHF averaged 52.3%, and 56.63% in box test trials. The CRI results ranged from 26.6% to 35.7%. Among the different percentages of plastics used, 3% plastic blends provided the most stable CSR results. The industrial furnaces work at temperatures between 1100 and 1350 degrees C and time coking 21 24h, compared to the test conditions achieved in the HHF and pilot furnace with box test. It was concluded that the results of CSR and CRI are consistent with the tests confirming the feasibility of using plastic in the steelmaking process. PMID- 27659867 TI - Geotechnical properties of municipal solid waste at Laogang Landfill, China. AB - Landfills have been widely constructed all around the world in order to properly dispose municipal solid waste (MSW). Understanding geotechnical properties of MSW is essential for the design and operation of landfills. A comprehensive investigation of geotechnical properties of MSW at the largest landfill in China was conducted, including waste composition, unit weight, void ratio, water content, hydraulic conductivity, and shear behavior. A large-scale rigid-wall permeameter and a direct-shear apparatus were adopted to test the hydraulic conductivity and shear behavior of the MSW, respectively. The composition of the MSW varied with age. With the depth increasing from 0 to 16m, the unit weight increased from 7.2 to 12.5kN/m3, while the void ratio decreased from 2.5 to 1.76. The water content ranged between 30.0% and 68.9% but did not show a trend with depth. The hydraulic conductivity of the MSW ranged between 4.6*10-4 and 6.7*10 3cm/s. It decreased as the dry unit weight increased and was sensitive to changes in dry unit weight in deeper layers. Displacement-hardening was observed during the whole shearing process and the shear strength increased with the normal stress, the displacement rate, and the unit weight. The friction angle and cohesion varied from (15.7 degrees , 29.1kPa) to (21.9 degrees , 18.3kPa) with depth increasing from 4 to 16m. The shear strength of the MSW obtained in this study was lower than the reported values in other countries, which was caused by the less fibrous materials in the specimens in this study. The results in this study will provide guidance in the design and operation of the landfills in China. PMID- 27659868 TI - Assessing thermal conductivity of composting reactor with attention on varying thermal resistance between compost and the inner surface. AB - Dynamic estimation of heat transfer through composting reactor wall was crucial for insulating design and maintaining a sanitary temperature. A model, incorporating conductive, convective and radiative heat transfer mechanisms, was developed in this paper to provide thermal resistance calculations for composting reactor wall. The mechanism of thermal transfer from compost to inner surface of structural layer, as a first step of heat loss, was important for improving insulation performance, which was divided into conduction and convection and discussed specifically in this study. It was found decreasing conductive resistance was responsible for the drop of insulation between compost and reactor wall. Increasing compost porosity or manufacturing a curved surface, decreasing the contact area of compost and the reactor wall, might improve the insulation performance. Upon modeling of heat transfers from compost to ambient environment, the study yielded a condensed and simplified model that could be used to conduct thermal resistance analysis for composting reactor. With theoretical derivations and a case application, the model was applicable for both dynamic estimation and typical composting scenario. PMID- 27659869 TI - Violence against children in Latin America and Caribbean countries: a comprehensive review of national health sector efforts in prevention and response. AB - BACKGROUND: Violence against children (VAC) remains a global problem. The health sector has an opportunity and responsibility to be part of the multi-sector collaboration to prevent and respond to VAC. This review aimed to assess the health sector's response to VAC among Latin American & Caribbean (LAC) countries, particularly as it relates to physical violence, sexual violence, and neglect. METHOD: National protocols for the identification and provision of health care to child survivors of violence, abuse and neglect were solicited in partnership with UNICEF and PAHO/WHO country offices within the LAC region. A parallel systematic review was undertaken in January 2015 to review studies published in the last 10 years that describe the regional health sector response to VAC. RESULTS: We obtained health sectors guidelines/protocols related to VAC from 22 of 43 (51 %) countries and reviewed 97 published articles/reports that met the review inclusion criteria. Country protocols were presented in Spanish (n = 12), Portuguese (n = 1), and English (n = 9). Thematic areas of country protocols included: 1) identifying signs and symptoms of VAC, 2) providing patient-centered care to the victim, and 3) immediate treatment of injuries related to VAC. The systematic review revealed that health professionals are often unaware of national protocols and lack training, resources, and support to respond to cases of VAC. Further, there is limited coordination between health and social protection services. CONCLUSIONS: VAC remains an international, public health priority. Health professionals are well-positioned to identify, treat and refer cases of VAC to appropriate institutions and community-based partners. However, poor protocol dissemination and training, limited infrastructure, and inadequate human resources challenge adherence to VAC guidelines. PMID- 27659870 TI - The problematic messages of nutritional discourse: A case-based critical media analysis. AB - Nutritional science has assumed a fundamental importance in shaping food meanings and practices in the developed world. This study critically analysed the content of one weekly nutrition column written by a nutritional expert in a popular New Zealand magazine, from a social constructionist perspective, to investigate how nutritional advice constructs food, food practices and eaters. The analysis identified a range of ways in which the nutrition information communicated in the articles was potentially problematic for readers. The articles advocated eating for health with recommendations based on nutritional science, but depicted nutritional information as inconclusive, changeable and open to interpretation. Fear-based messages were used to motivate making 'healthy' food choices, through linking 'unhealthy' food choices with fatness and chronic ill health. Unhealthy foods were portrayed as more enjoyable than healthy foods, social occasions involving food were constructed as problematic, and exercise was defined only as a way to negate food consumption. Healthy eating was portrayed as a matter of personal choice, obscuring the situational factors that impact on food choice and health. We conclude that the nutritional advice analysed in this study constructs a way of understanding food that, if internalised by eaters, may evoke anxiety, confusion and dissatisfaction around food and eating. PMID- 27659871 TI - Development and application of novelty pretreatment method for the concurrent quantitation of eleven water-soluble B vitamins in ultrafiltrates after renal replacement therapy. AB - Continous renal replacement therapy (CRRT) is particularly recommended for septic shock patients in intensive care units. The CRRT technique used most frequently is high volume continuous veno-venous haemofiltration. It provides a high rate of clearance of uremic toxins and inflammatory cytokines. However, it should also be taken into account that substances important for homeostasis may be concurrently unintentionally removed. Accordingly, water-soluble vitamins can be removed during continuous renal replacement therapy, and the estimate of the loss is critical to ensure appropriate supplementation. The aim of this work was to develop a simple methodology for a purification step prior to the LC-MS/MS determination of water-soluble vitamins in ultrafiltrate samples. For this purpose, two types of resin and a mix of resins were used as sorbents for the purification step. Moreover, parameters such as the amount of resin and the extraction time were optimized. The LC-MS/MS method was developed and validated for final determination of 11 vitamins. The results demonstrated the high purification capability of DEAE Sephadex resin with recoveries between 65 and 101% for water-soluble vitamins from ultrafiltrate samples. An optimized method was applied to assess the loss of B-group vitamins in patients after 24h of renal replacement therapy. The loss of vitamins B2, B6 pyridoxamine, B6 pyridoxal, B7, B1, and B5 in ultrafiltrates was similar in all patients. In the native ultrafiltrates, vitamins B6 pyridoxine, B9 and B12 were not detected. PMID- 27659872 TI - What causes trainees to leave oral and maxillofacial surgery? A questionnaire survey. AB - Understanding what causes trainees to leave OMFS is essential if we are to retain them within the specialty. Although these factors have been defined for medicine, we know of no previous study for OMFS. An online survey was distributed to roughly 1500 people who had registered an interest in OMFS during the past seven years. Personal information and details of education and employment were gathered along with personal factors that attracted them to OMFS. Of 251 trainees who responded, 50 (30%) were no longer interested. Factors that significantly correlated with an interest in OMFS included male sex (p=0.020), dual qualification (p=0.024), and (only for women) being single (p=0.024) and having no dependants (p=0.005). We used qualitative analysis to identify work-life balance, duration of training, and financial implications, as significant factors. Identification of key factors that affect OMFS trainees allows us to develop ways to keep them in the specialty. The predominant factor is work-life balance, and for women this included having children and being married. Financial issues related to the junior doctors' contract and competition ratios to second degrees, are also factors for both sexes. Also important are the "sunk costs" fallacy that causes some trainees to stay in training. This information can be used to help develop higher training, in negotiations of contracts, and to attract and retain future OMFS trainees. PMID- 27659874 TI - Perception of hierarchical boundaries in music and its modulation by expertise. AB - Hierarchical structure with units of different timescales is a key feature of music. For the perception of such structures, the detection of each boundary is crucial. Here, using electroencephalography (EEG), we explore the perception of hierarchical boundaries in music, and test whether musical expertise modifies such processing. Musicians and non-musicians were presented with musical excerpts containing boundaries at three hierarchical levels, including section, phrase and period boundaries. Non-boundary was chosen as a baseline condition. Recordings from musicians showed CPS (closure positive shift) was evoked at all the three boundaries, and their amplitude increased as the hierarchical level became higher, which suggest that musicians could represent music events at different timescales in a hierarchical way. For non-musicians, the CPS was only elicited at the period boundary and undistinguishable negativities were induced at all the three boundaries. The results indicate that a different and less clear way was used by non-musicians in boundary perception. Our findings reveal, for the first time, an ERP correlate of perceiving hierarchical boundaries in music, and show that the phrasing ability could be enhanced by musical expertise. PMID- 27659875 TI - Temporal dynamics of early visual word processing - Early versus late N1 sensitivity in children and adults. AB - In the course of reading development children become familiar with letter strings and learn to distinguish between lexical and non-lexical items. In previous studies, the N1 component of the ERP was shown to reflect print tuning but also to be sensitive to lexical effects. It remains unclear, however, whether these two aspects of orthographic processing occur at the same time or in different time windows during the lengthy N1 component. Moreover, it is unclear whether these processes develop late or occur already at early stages of literacy acquisition and whether this is similar for native languages and languages acquired later in life. To address these questions, 27 children were tested longitudinally, i.e. before (mean: 7.6 years) and after one year of classroom based English instruction. Additionally, 22 adult speakers of English as a foreign language (mean: 25.1 years) were investigated. A 128-channel EEG was recorded while participants performed a one-back task with native German words, English words, pseudowords and false-font strings. The event-related EEG analysis of early and late N1 phases revealed early effects related to print tuning and late effects related to lexical processing in the native, but not in the second language of adult readers. In the absence of lexicality effects in children, print tuning effects were found across both early and late N1 segments. The temporally distinct N1 sensitivities to print and lexicality reflect temporal dynamics of visual word processing, which seem to depend on reading expertise or maturation. PMID- 27659876 TI - Hemodynamic evaluation in patients with transposition of the great arteries after the arterial switch operation: 4D flow and 2D phase contrast cardiovascular magnetic resonance compared with Doppler echocardiography. AB - BACKGROUND: Peak velocity measurements are used to evaluate the significance of stenosis in patients with transposition of the great arteries after the arterial switch operation (TGA after ASO). 4D flow cardiovascular magnetic resonance (CMR) provides 3-directional velocity encoding and full volumetric coverage of the great arteries and may thus improve the hemodynamic evaluation in these patients. The aim of this study was to compare peak velocities measured by 4D flow CMR with 2D phase contrast (PC) CMR and the gold standard Doppler echocardiography (echo) in patients with TGA after ASO. METHODS: Nineteen patients (mean age 13 +/- 9 years, range 1-25 years) with TGA after ASO who underwent 2D PC CMR and 4D flow CMR were included in this study. Peak velocities were measured with 4D flow CMR in the aorta and pulmonary arteries and compared to peak velocities measured with 2D PC CMR and Doppler echo. 2D PC CMR data were available in the ascending aorta, main, right and left pulmonary arteries (AAO/MPA/RPA/LPA) for 19/18/17/17 scans, respectively, and Doppler echo data were available for 13/9/6/6 scans, respectively. Peak velocities were measured with: 1) a single cross section for 2D PC CMR, 2) velocity maximum intensity projections (MIPs) for 4D flow CMR and 3) Doppler echo. RESULTS: Significantly higher peak velocities were found with 4D flow CMR than 2D PC CMR in the AAO (p = 0.003), MPA (p = 0.002) and RPA (p = 0.005) but not in the LPA (p = 0.200). No difference in peak velocity was found between 4D flow CMR and Doppler echo (p > 0.46) or 2D PC CMR and echo (p > 0.11) for all analyzed vessel segments. CONCLUSIONS: 4D flow CMR evaluation of patients with TGA after ASO detected higher peak velocities than 2D PC CMR, indicating the potential of 4D flow CMR to provide improved stenosis assessment in these patients. PMID- 27659877 TI - Physiological mechanisms of pulmonary hypertension. AB - Pulmonary hypertension is usually related to obstruction of pulmonary blood flow at the level of the pulmonary arteries (eg, pulmonary embolus), pulmonary arterioles (idiopathic pulmonary hypertension), pulmonary veins (pulmonary venoocclusive disease) or mitral valve (mitral stenosis and regurgitation). Pulmonary hypertension is also observed in heart failure due to left ventricle myocardial diseases regardless of the ejection fraction. Pulmonary hypertension is often regarded as a passive response to the obstruction to pulmonary flow. We review established fluid dynamics and physiology and discuss the mechanisms underlying pulmonary hypertension. The important role that the right ventricle plays in the development and maintenance of pulmonary hypertension is discussed. We use principles of thermodynamics and discuss a potential common mechanism for a number of disease states, including pulmonary edema, through adding pressure energy to the pulmonary circulation. PMID- 27659878 TI - Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial (WRAP-IT). AB - BACKGROUND: Cardiac implantable electronic device (CIED) infection is a major complication that is associated with significant morbidity and mortality. The aim of this study is to determine whether Medtronic TYRX absorbable envelope reduces the risk of CIED infection through 12 months of follow-up post procedure. METHODS: WRAP-IT is a randomized, prospective, multi center, international, single-blinded study. Up to 7,764 subjects who are undergoing CIED generator replacement, upgrade, or revision, or a de novo CRT-D implant, will be enrolled and randomized (1:1) to receive the TYRX envelope or not. The primary endpoint is major CIED infection throughout 12 months of follow up after the procedure. Data will be analyzed with an intention to treat approach. WRAP-IT will also assess the performance of Medtronic's lead monitoring algorithms in subjects whose CIED includes a transvenous right ventricular defibrillation system. CONCLUSIONS: WRAP IT is a large randomized clinical trial that will assess the efficacy of TYRX absorbable envelope in reducing CIED infection, define its cost effectiveness, and will also provide a unique opportunity to better understand the pathophysiology and risk factors for CIED infection. PMID- 27659879 TI - Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction. AB - BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. DESIGN: The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 * ULN, total bilirubin >2 * ULN, serum creatinine >=1.5*baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. SUMMARY: The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo. PMID- 27659873 TI - GRIM-19: A master regulator of cytokine induced tumor suppression, metastasis and energy metabolism. AB - Cytokines induce cell proliferation or growth suppression depending on the context. It is increasingly becoming clear that success of standard radiotherapy and/or chemotherapeutics to eradicate solid tumors is dependent on IFN signaling. In this review we discuss the molecular mechanisms of tumor growth suppression by a gene product isolated in our laboratory using a genome-wide expression knock down strategy. Gene associated with retinoid-IFN-induced mortality -19 (GRIM-19) functions as non-canonical tumor suppressor by antagonizing oncoproteins. As a component of mitochondrial respiratory chain, GRIM-19 influences the degree of "Warburg effect" in cancer cells as many advanced and/or aggressive tumors show severely down-regulated GRIM-19 levels. In addition, GRIM-19 appears to regulate innate and acquired immune responses in mouse models. Thus, GRIM-19 is positioned at nodes that favor cell protection and/or prevent aberrant cell growth. PMID- 27659880 TI - Effects of statin therapy on progression of mild noncalcified coronary plaque assessed by serial coronary computed tomography angiography: A multicenter prospective study. AB - BACKGROUND: There are limited data assessing statin therapy in patients with nonobstructive coronary plaque on coronary computed tomography angiography (CCTA). METHODS: Two hundred six consecutive patients with mild noncalcified plaque on CCTA were enrolled in this multicenter prospective observational study. Subjects were divided into 3 groups according to subsequent statin therapy: intensive statin therapy (n = 55), moderate statins (n = 85), and no statin (n = 66). Serial scans were performed after a median interval of 18 months. Low attenuation plaque (LAP) volume, total plaque volume, and percent plaque volume were measured. RESULTS: The LAP volume, total plaque volume, and percent plaque volume showed significant regression among intensive-statin compared with no statin group (annualized changes: -7.1 +/- 13.1 vs 0.9 +/- 12.7 mm(3), P< .001; 16.4 +/- 35.0 vs 12.3 +/- 32.4 mm(3), P< .001; and -6.2% +/- 11.8% vs 3.5% +/- 12.1%, P< .001, respectively). Progression of LAP volume, total plaque volume, and percent plaque volume was retarded among moderate-statin compared with no statin group (annualized changes: -2.8 +/- 7.6 vs 0.9 +/- 12.7 mm(3), P= .041; 0.1 +/- 25.6 vs 12.3 +/- 32.4 mm(3), P= .014; and -1.8% +/- 11.2% vs 3.5% +/- 12.1%, P= .006, respectively). On multivariable model predicting change in total plaque volume, higher baseline LAP volume, moderate statin therapy, and intensive statin therapy were each independent predictors of plaque regression (standardized coefficients: baseline LAP volume -0.36, P< .001; moderate statin 0.21, P= .004; intensive statin -0.36, P< .001, respectively). CONCLUSIONS: This study suggests that statin treatment can retard progression and even induce regression of mild noncalcified coronary plaque. Patients with greater baseline LAP volume are more likely to benefit from statin therapy. PMID- 27659881 TI - Coronary angiography after cardiac arrest: Rationale and design of the COACT trial. AB - BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated. HYPOTHESIS: We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post-cardiac arrest patients without signs of STEMI. DESIGN: In a prospective, multicenter, randomized controlled clinical trial, 552 post-cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90 day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment. SUMMARY: The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post-cardiac arrest patients without STEMI on 90-day survival. PMID- 27659883 TI - Cholesterol efflux capacity: An introduction for clinicians. AB - Epidemiologic studies have shown an inverse correlation between high-density lipoprotein (HDL) cholesterol (HDL-C) levels and cardiovascular disease outcomes. However, the hypothesis of a causal relationship between HDL-C and cardiovascular disease has been challenged by genetic and clinical studies. Serum cholesterol efflux capacity (CEC) is an important measure of HDL function in humans. Recent large clinical studies have shown a correlation between in vitro CEC and cardiovascular disease prevalence and incidence, which appears to be independent of HDL-C concentration. The present review summarizes recent large clinical studies and introduces important methodological considerations. Further studies are required to standardize and establish the reproducibility of this measure of HDL function and clarify whether modulating CEC will emerge as a useful therapeutic target. PMID- 27659884 TI - Exploring cognitive bias in destination therapy left ventricular assist device decision making: A retrospective qualitative framework analysis. AB - BACKGROUND: Cognitive biases are psychological influences, which cause humans to make decisions, which do not seemingly maximize utility. For people with heart failure, the left ventricular assist device (LVAD) is a surgically implantable device with complex tradeoffs. As such, it represents an excellent model within which to explore cognitive bias in a real-world decision. We conducted a framework analysis to examine for evidence of cognitive bias among people deciding whether or not to get an LVAD. OBJECTIVES: The aim of this study was to explore the influence of cognitive bias on the LVAD decision-making process. METHODS: We analyzed previously conducted interviews of patients who had either accepted or declined an LVAD using a deductive, predetermined framework of cognitive biases. We coded and analyzed the interviews using an inductive deductive framework approach, which also allowed for other themes to emerge. RESULTS: We interviewed a total of 22 heart failure patients who had gone through destination therapy LVAD decision making (15 who had accepted the LVAD and 7 who had declined). All patients appeared influenced by state dependence, where both groups described high current state of suffering, but the groups differed in whether they believed LVAD would relieve suffering or not. We found evidence of cognitive bias that appeared to influence decision making in both patient groups, but groups differed in terms of which cognitive biases were present. Among accepters, we found evidence of anchoring bias, availability bias, optimism bias, and affective forecasting. Among decliners, we found evidence of errors in affective forecasting. CONCLUSIONS: Medical decision making is often a complicated and multifaceted process that includes cognitive bias as well as other influences. It is important for clinicians to recognize that patients can be affected by cognitive bias, so they can better understand and improve the decision-making process to ensure that patients are fully informed. PMID- 27659882 TI - Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND: Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. METHODS: We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and beta2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. RESULTS: Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus >=90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs <=2.7 for the other kidney markers). CONCLUSIONS: Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context. PMID- 27659885 TI - The effect of high-risk ST elevation myocardial infarction transfer patients on risk-adjusted in-hospital mortality: A report from the American Heart Association Mission: Lifeline program. AB - BACKGROUND: Hospital mortality is an important quality measure for acute myocardial infarction care. There is a concern that despite risk adjustment, percutaneous coronary intervention hospitals accepting a greater volume of high risk ST elevation myocardial infarction (STEMI) transfer patients may have their reported mortality rates adversely affected. METHODS: The STEMI patients in the National Cardiovascular Data RegistryAcute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines from April 2011 to December 2013 were included. High-risk STEMI was defined as having either cardiogenic shock or cardiac arrest on first medical contact. Receiving hospitals were divided into tertiles based on the ratio of high-risk STEMI transfer patients to the total number of STEMI patients treated at each hospital. Using the Action Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines in-hospital mortality risk model, we calculated the difference in risk standardized in-hospital mortality before and after excluding high-risk STEMI transfers in each tertile. RESULTS: Among 119,680 STEMI patients treated at 539 receiving hospitals, 37,028 (31%) were transfer patients, of whom 4,500 (12%) were highrisk. The proportion of high-risk STEMI transfer patients ranged from 0% to 12% across hospitals. Unadjusted mortality rates in the low-, middle-, and high-tertile hospitals were 6.0%, 6.0%, and 5.9% among all STEMI patients and 6.0%, 5.5%, and 4.6% after excluding high-risk STEMI transfers. However, risk standardized hospital mortality rates were not significantly changed after excluding high-risk STEMI transfer patients in any of the 3 hospital tertiles (low, -0.04%; middle, -0.05%; and high, 0.03%). CONCLUSIONS: Risk-adjusted in hospital mortality rates were not adversely affected in STEMI-receiving hospitals who accepted more high-risk STEMI transfer patients when a clinical mortality risk model was used for risk adjustment. PMID- 27659886 TI - Ischemic and bleeding events in patients with myocardial infarction undergoing percutaneous coronary intervention who require oral anticoagulation: Insights from the Canadian observational AntiPlatelet sTudy. AB - BACKGROUND: Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12ris), practice patterns and associated clinical outcomes in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and also requiring oral anticoagulation (OAC) have not been fully characterized. METHODS: The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, December 2011 to May 2013) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI. We describe the clinical characteristics, treatment patterns, bleeding, and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual-antiplatelet therapy (DAPT) (acetyl salicylic acid [ASA]+P2Y12ri) or triple therapy (ASA+P2Y12ri+OAC). RESULTS: Of the 2,034 patients at discharge, 86% (n = 1,757) were on DAPT, whereas 14% (n = 277) were on triple therapy (50% warfarin, 50% non-vitamin K OAC [NOAC]). The frequency of newer P2Y12ri use (prasugrel or ticagrelor) was similar in the DAPT and triple therapy groups (28% vs 26%, respectively). In the triple therapy group, NOAC use was higher in those receiving a new P2Y12ri compared to those receiving clopidogrel (75% vs 41%, respectively, P < .0001). The unadjusted and adjusted events of major cardiovascular event (MACE) and bleeding were higher in the triple therapy group. For patients on triple therapy, the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel. CONCLUSION: In this observational study of MI patients requiring PCI, 1 in 8 were discharged on triple antithrombotic therapy, of whom 26% were on newer P2Y12ris. Patients on triple therapy had higher risk at baseline, with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone. Among triple therapy-treated patients, there was no difference in the MACE and bleeding events regardless of the P2Y12ri used. PMID- 27659888 TI - Association between periodontitis and arterial hypertension: A systematic review and meta-analysis. AB - BACKGROUND: Several studies have shown that periodontal diseases are associated with hypertension (HT). However, heterogeneity among populations, diagnosis criteria, and shared risk factors represent some difficulties in terms of interpretation. Therefore, the aim of this study was to determine the magnitude of the association between periodontal diseases and HT. METHODS AND RESULTS: A systematic review and meta-analysis, including studies published up to June 2016, have been performed. Sixteen studies assessing the association between periodontal diseases and HT have been included. The meta-analysis considering all included studies (moderate to severe periodontitis) showed that the presence of HT was associated with the presence of periodontal diseases (OR, 1.50; 95% CI, 1.27-1.78). To reduce potential bias, a stratified analysis has been performed illustrating the impact of inclusion criteria and adjustments on the magnitude of the association. Interestingly, when only studies with secure diagnosis of severe periodontitis and HT were considered, an OR=1.64 (95% CI, 1.23-2.19) has been measured. CONCLUSIONS: Periodontal diseases are associated with a higher risk of HT especially for severe periodontitis. However, no conclusions could be made regarding the causative involvement of periodontal diseases mainly due to the reduced number of available prospective studies and remaining questions regarding underlying biological mechanisms. PMID- 27659887 TI - Rationale and design of the Study of a Tele-pharmacy Intervention for Chronic diseases to Improve Treatment adherence (STIC2IT): A cluster-randomized pragmatic trial. AB - BACKGROUND: Approximately half of patients with chronic cardiometabolic conditions are nonadherent with their prescribed medications. Interventions to improve adherence have been only modestly effective because they often address single barriers to adherence, intervene at single points in time, or are imprecisely targeted to patients who may not need adherence assistance. OBJECTIVE: To evaluate the effect of a multicomponent, behaviorally tailored pharmacist-based intervention to improve adherence to medications for diabetes, hypertension, and hyperlipidemia. TRIAL DESIGN: The STIC2IT trial is a cluster randomized pragmatic trial testing the impact of a pharmacist-led multicomponent intervention that uses behavioral interviewing, text messaging, mailed progress reports, and video visits. Targeted patients are those who are nonadherent to glucose-lowering, antihypertensive, or statin medications and who also have evidence of poor disease control. The intervention is tailored to patients' individual health barriers and their level of health activation. We cluster randomized 14 practice sites of a large multispecialty group practice to receive either the pharmacist-based intervention or usual care. STIC2IT has enrolled 4,076 patients who will be followed up for 12months after randomization. The trial's primary outcome is medication adherence, assessed using pharmacy claims data. Secondary outcomes are disease control and health care resource utilization. CONCLUSION: This trial will determine whether a technologically enabled, behaviorally targeted pharmacist-based intervention results in improved adherence and disease control. If effective, this strategy could be a scalable method of offering tailored adherence support to those with the greatest clinical need. PMID- 27659889 TI - Insights from cardiac imaging after ST-elevation myocardial infarction: Will increased recognition of patients at risk translate into improved long-term outcomes? PMID- 27659890 TI - Adverse diastolic remodeling after reperfused ST-elevation myocardial infarction: An important prognostic indicator. AB - OBJECTIVES: We sought to determine the relationship of adverse diastolic remodeling (ie, worsening diastolic or persistent restrictive filling) with infarct scar characteristics, and to evaluate its prognostic value after ST segment elevation myocardial infarction (STEMI). BACKGROUND: Severe diastolic dysfunction (restrictive filling) has known prognostic value post STEMI. However, ongoing left ventricular (LV) remodeling post STEMI may alter diastolic function even if less severe. METHODS AND RESULTS: There were 218 prospectively recruited STEMI patients with serial echocardiograms (transthoracic echocardiography) and cardiac magnetic resonance imaging (CMR) performed, at a median of 4 days (early) and 55 days (follow-up). LV ejection fraction and infarct characteristics were assessed by CMR, and comprehensive diastolic function assessment including a diastolic grade was evaluated on transthoracic echocardiography. 'Adverse diastolic remodeling' occurred if diastolic function grade either worsened (>=1 grade) between early and follow-up imaging, or remained as persistent restrictive filling at follow-up. Follow-up infarct scar size (IS) predicted adverse diastolic remodeling (area under the curve 0.86) and persistent restrictive filling (area under the curve 0.89). The primary endpoint of major adverse cardiovascular events (MACE) occurred in 48 patients during follow-up (mean, 710+/-79 days). Kaplan-Meier analysis showed that adverse diastolic remodeling (n=50) and persistent restrictive filling alone (n=33) were significant predictors of MACE (both P<.001). Multivariate Cox analysis, when adjusted for TIMI risk score and CMR IS, microvascular obstruction, and LV ejection fraction, showed adverse diastolic remodeling (HR 3.79, P<.001) was an independent predictor of MACE, as was persistent restrictive filling alone (HR 2.61, P=.019). CONCLUSIONS: Larger IS is associated with adverse diastolic remodeling. Following STEMI, adverse diastolic remodeling is a powerful prognostic marker, and identifies a larger group of 'at-risk' patients, than does persistent restrictive filling alone. PMID- 27659891 TI - Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. PMID- 27659892 TI - Reply to letter to the editor by Kintur Sanghvi, MD; Allen McGrew, DO; and Kiran Hegde, BE, MBA. PMID- 27659893 TI - The narrative review on morphine in acute coronary syndrome: Recognizing opioidergic cardioprotection. PMID- 27659894 TI - The narrative review on morphine in acute coronary syndrome: Recognizing opioidergic cardioprotection-reply. PMID- 27659895 TI - Significance of Echocardiographically Detected Central Venous Catheter Tip Associated Thrombi. AB - PURPOSE: To explore significance, management, and outcomes of central venous catheter (CVC) tip-associated thrombi incidentally detected on echocardiography. MATERIALS AND METHODS: Echocardiogram data from all patients with CVCs from October 2009 to June 2011 were reviewed (N = 170). Patients with CVC tip associated thrombi were selected (n = 49). Echocardiograms were reviewed for ejection fraction, presence of patent foramen ovale (PFO), presence of other intracardiac shunts, and mean thrombus size. Management decisions, thrombus extension, pulmonary embolism, paradoxical emboli, and stroke within 3 months were recorded. RESULTS: Mean thrombus size was 2.1 cm (range, 0.5-5.7 cm). Of patients with thrombi, 11 (22%) were already on anticoagulation, and there was no change in management. Anticoagulation was started without complications in 17 (35%) patients, the catheter was removed in 4 (8%) patients, and no new treatment was initiated in 17 (35%) patients. Of these 17 patients, 16 (94%) developed no complications. One (6%) patient with a PFO and right-to-left shunt experienced a stroke before PFO closure. After surgical closure of the PFO, the same patient developed catheter tip-associated thrombus without complication. There were no pulmonary emboli, strokes, or other detected embolic phenomena. CONCLUSIONS: In this sample with CVC tip-associated thrombi but without PFO or other intracardiac shunts, no embolic or other complications were detected, regardless of anticoagulation status. These data suggest a benign course for such thrombi and that anticoagulation, catheter removal, thrombectomy, and thrombolysis may be unnecessary when catheter tip-associated thrombi are incidentally detected on echocardiography. PMID- 27659896 TI - Pregnancy and the hair growth cycle: anagen induction against hair growth disruption using Nourkrin(r) with Marilex(r) , a proteoglycan replacement therapy. AB - Postpartum effluvium is a well-known clinical fact. However, following some minor research activities in the 1960s, very little has happened on the research front of the subject. It was hypothesized that postpartum hair loss might be a manifestation of a change in the hair growth cycle occurring normally during pregnancy. Recently, new research has been published trying to explain the mechanism of action behind this frequently occurring hair growth disruption, and to develop a functional treatment schedule and regime. Under normal circumstances, postpartum effluvium will disappear by itself as a function of time, and therefore adequate information to the patient is important in order to reduce the anxiety that it will not be a permanent problem. However, in some subjects it can manifest itself for longer stages and even become permanent. At the present time, treatments aim at correcting underlying hormonal imbalances and at improving overall cosmetic appearance. Several treatments in the form of thyroid supplementation, topical progesterone and estradiol lotions, and even oral contraceptive have been studied. All the available studies have significant limitations in their scientific basis, such as small sample size, absence of control group, or highly subjective measurement of treatment response. It is evident from the available studies that no specific treatment has been investigated thoroughly enough to justify recommendation in clinical treatment or to be termed "effective." Without the ability to provide a pathogenic diagnosis or causality criteria, chances are low that a treatment by trial and error will adequately be able to control hair effluvium. Current hair treatment strategies are symptomatic and nonspecific; therefore, future research must aim at developing new and targeted methods with a point of departure in observing concomitant biological mechanisms. Based on the research in the 1960s, current knowledge about the hair follicle and the regulation of the hair cycles, we believe that an anagen inducer in the form of a specific proteoglycan replacement therapy (Nourkrin(r) with Marilex(r) from Pharma Medico) could be a proper solution to shorten the hair eclipse phenomenon - and give the patient a feeling of control and empowerment. PMID- 27659897 TI - Effectiveness and cost-effectiveness of telephone consultations for fever or gastroenteritis using a formalised procedure in general practice: study protocol of a cluster randomised controlled trial. AB - BACKGROUND: Telephone consultations in general practice are on the increase. However, data on their efficiency in terms of out-of-hours general practitioner (GP) workload, visits to hospital emergency departments (ED), cost, patient safety and satisfaction are relatively scant. The aim of this trial is to assess the effectiveness of telephone consultations provided by French emergency call centres in patients presenting with isolated fever or symptoms of gastroenteritis, mainly encountered diseases. METHODS/DESIGN: This is a prospective, open-label, multicentre, pragmatic, cluster randomised clinical trial of an estimated 2880 patients making an out-of-hours call to one of six French emergency call centres for assistance with either fever or symptoms of gastroenteritis without seriousness criteria. Each call is handled by a call centre physician. Out-of-hours is 8 p.m. to 7.59 a.m. on weekdays, 1 p.m. to 7.59 a.m. on Saturdays and round-the-clock on Sundays and school holidays. Patients will be enrolled over 1 year. In the intervention arm, a telephone consultation based on a protocol, the formal Telephone Medical Advice (fTMA), is offered to each patient calling. This protocol aims to overcome a physical consultation during out-of-hours periods. It offers reassurance and explanations, advice on therapeutic management which may include, in addition to hygiene and diet measures, a telephone prescription of antipyretic, analgesic, rehydration medication or others, and recommendations on surveillance of the patient and any action to be taken. The patient is invited to call again if the condition worsens or new symptoms develop and to make an appointment with their family GP during office hours. In the control arm, the call centre physician handles calls as usual. This physician can carry out a telephone consultation with or without a telephone prescription, dispatch an on-duty GP, the fire brigade or an ambulance to the patient, or refer the patient to an on-duty physician or to the ED. Each patient will receive a follow-up call on day 15. The primary endpoint is the frequency of out-of-hours, face-to-face GP consultations or visits to the ED during the 15 days following the index call. The secondary endpoints measured on day 15 are the number of stays in intensive care, the number of hospital admissions, the number of interventions by the fire brigade, emergency medical and ambulance services, the number and length of prescribed sick-leave episodes, all-cause mortality, morbidity, clinical outcome, patient compliance, patient satisfaction, the number of renewed calls to the call centre, the number of patients receiving multiple face-to-face GP consultations and costs incurred. DISCUSSION: This trial will assess the effectiveness and the cost-effectiveness of a formalised response to calls for assistance with fever or symptoms of gastroenteritis without seriousness criteria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02286245 , registered on 9 September 2014. PMID- 27659898 TI - Reducing exposure to pathogens in the horse: a preliminary study into the survival of bacteria on a range of equine bedding types. AB - AIMS: To compare the rate of growth of four microbial strains that cause disease in the horse, on four commonly used types of bedding. The moisture-holding capacity of each bedding type was also tested. METHODS AND RESULTS: Microbial strains included Streptococcus equi, Streptococcus zooepidemicus, Fusobacterium necrophorum, Dichelobacter nodosus and Dermatophilus congolensis. The bedding types tested were Pinus sylvestris (Scots pine shavings), Pinus nigra (Corsican pine shavings), Picea sitchensis (Sitka spruce shavings), Cannabis sativa (hemp) and chopped wheat straw. A suspension of each microbial strain was spread in triplicate on agar media and incubated in its optimal growth conditions. The viable count (colony-forming unit per ml) was determined for each bacterial strain for the five different bedding types. Pinus sylvestris bedding resulted in significantly less (P = 0.001) bacterial growth of all strains tested. CONCLUSIONS: Factors resulting in the inhibition of bacterial growth include the antibacterial effects reported in the Pinacea family and the physical properties of the bedding substrate. Research is currently focussed on the diagnosis and management of disease. Prevention of disease is also important for matters of biosecurity. Strategies should include the provision of a hygienic environment and the use of specific types of bedding. SIGNIFICANCE AND IMPACT OF THE STUDY: Bedding choice has implications for global equine health and disease prevention as well as potential benefits in other animal species. PMID- 27659899 TI - Nemaline myopathies: State of the art. AB - Nemaline myopathy (NM) is one of the most common forms of congenital myopathy. The condition is defined by the histopathological finding of nemaline bodies (rods) on muscle biopsy and is associated with hypotonia and muscle weakness. The clinical spectrum encompasses lethal forms presenting in the neonatal period with profound weakness and less severe congenital diseases of later onset. NM is significantly heterogeneous from a genetic point of view, and its inheritance can be autosomal-dominant (AD), sporadic or autosomal-recessive (AR). To date, 11 genes encoding proteins of skeletal muscle thin filaments, Kelch domain associated proteins and an unconventional myosin have been implicated in NM. The mechanisms leading to nemaline body formation and muscle weakness are still largely unclear. This report reviews the clinical, histopathological and genetic features of NM, with a focus on some of the recently discovered forms. PMID- 27659900 TI - Guillain-Barre syndrome: What have we learnt during one century? A personal historical perspective. AB - We are approaching the centenary of the first description of Guillain-Barre syndrome. The past 30 years had witnessed an amazing progress in the understanding of the immunological and pathological mechanisms of this disorder. We now recognize that Guillain-Barre syndrome is remarkably heterogeneous and under this umbrella term are several variants and subtypes with distinct clinical, electrophysiological and immunopathological features. This review is a historical journey, through a personal perspective, following the milestones that led to the current substantial knowledge of Guillain-Barre syndrome. PMID- 27659901 TI - High-quality reference transcript datasets hold the key to transcript-specific RNA-sequencing analysis in plants. AB - 525 I. 525 II. 526 III. 527 IV. 527 V. 529 VI. 529 529 References 529 SUMMARY: Re programming of the transcriptome involves both transcription and alternative splicing (AS). Some genes are regulated only at the AS level with no change in expression at the gene level. AS data must be incorporated as an essential aspect of the regulation of gene expression. RNA-sequencing (RNA-seq) can deliver both transcriptional and AS information, but accurate methods to analyse the added complexity in RNA-seq data are needed. The construction of a comprehensive reference transcript dataset (RTD) for a specific plant species, variety or accession, from all available sequence data, will immediately allow more robust analysis of RNA-seq data. RTDs will continually evolve and improve, a process that will be more efficient if resources across a community are shared and pooled. PMID- 27659902 TI - Review of flavonoids: A diverse group of natural compounds with anti-Candida albicans activity in vitro. AB - Flavonoids are a subdivision of polyphenols, a versatile class of natural compounds that represent secondary metabolites from higher plants and are abundant in human diet. Various protective effects of flavonoids have been reported, including antimicrobial and antifungal activities. Due to the nature of oral candidiasis and the increased use of antifungal agents, several drug resistant strains have emerged making it impractical to rely on one standard therapeutic regime. The aim of this review is to summarize the antifungal activity of some examples of the major subclasses of flavonoids in pure extract forms against C. albicans in vitro, as reported in literature over the past 10 years (2004-2015). In addition, this review outlines the potential mechanism of actions of flavonoids studied in vitro, which may contribute to a better understanding of flavonoids as multi-targets agents in the treatment and/or prevention of oral candidiasis in clinical settings. PMID- 27659903 TI - Incidences and variations of hospital acquired venous thromboembolism in Australian hospitals: a population-based study. AB - BACKGROUND: Data on hospital-acquired venous thromboembolism (HA-VTE) incidence, case fatality rate and variation amongst patient groups and health providers is lacking. We aim to explore HA-VTE incidences, associated mortality, trends and variations across all acute hospitals in New South Wales (NSW)-Australia. METHODS: A population-based study using all admitted patients (aged 18-90 with a length of stay of at least two days and not transferred to another acute care facility) in 104 NSW acute public and private hospitals during 2002-2009. Poisson mixed models were used to derive adjusted rate ratios (IRR) in presence of patient and hospital characteristics. RESULTS: Amongst, 3,331,677 patients, the incidence of HA-VTE was 11.45 per 1000 patients and one in ten who developed HA VTE died in hospital. HA-VTE incidence, initially rose, but subsequently declined, whereas case fatality rate consistently declined by 22 % over the study period. Surgical patients were 128 % (IRR = 2.28, 95 % CI: 2.19-2.38) more likely to develop HA-VTE, but had similar case fatality rates compared to medical patients. Private hospitals, in comparison to public hospitals had a higher incidence of HA-VTE (IRR = 1.76; 95 % CI: 1.42-2.18) for medical patients. However, they had a similar incidence (IRR = 0.91; 95 % CI: 0.75-1.11), but a lower mortality (IRR = 0.59; 95 % CI: 0.47-0.75) amongst surgical patients. Smaller public hospitals had a lower HA-VTE incidence rate compared to larger hospitals (IRR < 0.68) but a higher case fatality rate (IRR > 1.71). Hospitals with a lower reported HA-VTE incidence tended to have a higher HA-VTE case fatality rate. CONCLUSION: Despite the decline in HA-VTE incidence and case fatality, there were large variations in incidents between medical and surgical patients, public and private hospitals, and different hospital groups. The causes of such differences warrant further investigation and may provide potential for targeted interventions and quality improvement initiatives. PMID- 27659905 TI - Clonidine to treat Irukandji syndrome. PMID- 27659904 TI - Psychometric Evaluation of the Comprehensive Trauma Interview PTSD Symptoms Scale Following Exposure to Child Maltreatment. AB - The current study evaluated the psychometric properties of the Comprehensive Trauma Interview Post-Traumatic Stress Disorder (PTSD) Symptoms Scale (CTI-PSS), a novel method of assessing PTSD symptoms following exposure to a range of child adversities in the child maltreatment population. A sample of female adolescents ( n = 343) exposed to substantiated child sexual abuse and a nonmaltreated comparison condition completed the CTI-PSS and other established measures to assess internal consistency, factor structure, test discriminability as well as convergent, discriminant, and incremental validities. Results demonstrated that the CTI-PSS is a reliable and valid measure of PTSD symptoms with good discriminability and a factor structure that fits existing conceptualizations of the PTSD construct. It also demonstrated strong convergence with an established measure of PTSD symptoms and explained unique variance in the prediction of child sexual abuse status. Overall, the CTI-PSS appears to be a useful instrument for assessing PTSD symptoms in the child maltreatment population. PMID- 27659907 TI - Discrimination of sleep states using continuous cerebral bedside monitoring (amplitude-integrated electroencephalography) compared to polysomnography in infants. AB - AIM: Limited two-channel electroencephalography (EEG) and amplitude-integrated EEG (aEEG) monitorings are being increasingly used; however, these measurements have not been compared with polysomnographic monitoring, the gold standard for determining infant sleep states. We aimed to determine the accuracy of two channel EEG and aEEG recordings in defining sleep states and wakefulness in term infants compared to polysomnographic monitoring. METHODS: Sleep was assessed in eight healthy term born infants (mean: 34 +/- 3 days), using simultaneous polysomnography (Compumedics S-Series) and a two-channel EEG monitor (Brainz BRM2). EEG intensity, 90% spectral edge frequency (SEF), aEEG amplitude frequency bands were analysed in 30-second epochs during quiet sleep, active sleep and awake as determined by polysomnography. RESULTS: BRM2-recorded EEG accurately identified quiet sleep from active sleep for EEG intensity (p = 0.003), SEF (p = 0.001) and aEEG amplitude (p = 0.003) and quiet sleep from awake, but not active sleep from awake. Frequency band analysis showed that wake could be identified by changes in absolute power (p = 0.015) and frequency as a percentage of total power (p = 0.03). CONCLUSION: We demonstrate that limited two-channel EEG monitoring can distinguish quiet sleep from active sleep and may be suitable for investigating the development of sleep in infants in the neonatal intensive care setting. PMID- 27659909 TI - Optimization of the short-circuit current in an InP nanowire array solar cell through opto-electronic modeling. AB - InP nanowire arrays with axial p-i-n junctions are promising devices for next generation photovoltaics, with a demonstrated efficiency of 13.8%. However, the short-circuit current in such arrays does not match their absorption performance. Here, through combined optical and electrical modeling, we study how the absorption of photons and separation of the resulting photogenerated electron hole pairs define and limit the short-circuit current in the nanowires. We identify how photogenerated minority carriers in the top n segment (i.e. holes) diffuse to the ohmic top contact where they recombine without contributing to the short-circuit current. In our modeling, such contact recombination can lead to a 60% drop in the short-circuit current. To hinder such hole diffusion, we include a gradient doping profile in the n segment to create a front surface barrier. This approach leads to a modest 5% increase in the short-circuit current, limited by Auger recombination with increased doping. A more efficient approach is to switch the n segment to a material with a higher band gap, like GaP. Then, a much smaller number of holes is photogenerated in the n segment, strongly limiting the amount that can diffuse and disappear into the top contact. For a 500 nm long top segment, the GaP approach leads to a 50% higher short-circuit current than with an InP top segment. Such a long top segment could facilitate the fabrication and contacting of nanowire array solar cells. Such design schemes for managing minority carriers could open the door to higher performance in single- and multi junction nanowire-based solar cells. PMID- 27659908 TI - Pentraxin 3 recruits complement factor H to protect against oxidative stress induced complement and inflammasome overactivation. AB - The discovery that genetic abnormalities in complement factor H (FH) are associated with an increased risk for age-related macular degeneration (AMD), the most common cause of blindness among the elderly, raised hope of new treatments for this vision-threatening disease. Nonetheless, over a decade after the identification of this important association, how innate immunity contributes to AMD remains unresolved. Pentraxin 3 (PTX3), an essential component of the innate immunity system that plays a non-redundant role in controlling inflammation, regulates complement by interacting with complement components. Here, we show that PTX3 is induced by oxidative stress, a known cause of AMD, in the retinal pigmented epithelium (RPE). PTX3 deficiency in vitro and in vivo magnified complement activation induced by oxidative stress, leading to increased C3a, FB, and C3d, but not C5b-9 complex formation. Increased C3a levels, resulting from PTX3 deficiency, raised the levels of Il1b mRNA and secretion of activated interleukin (IL)-1beta by interacting with C3aR. Importantly, PTX3 deficiency augmented NLRP3 inflammasome activation, resulting in enhanced IL-1beta, but not IL-18, production by the RPE. Thus, in the presence of PTX3 deficiency, the complement and inflammasome pathways worked in concert to produce IL-1beta in sufficient abundance to, importantly, result in macrophages accumulating in the choroid. These results demonstrate that PTX3 acts as an essential brake for complement and inflammasome activation by regulating the abundance of FH in the RPE, and provide critical insights into the complex interplay between oxidative stress and innate immunity in the early stages of AMD development. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27659906 TI - Growth and development of Arabidopsis thaliana under single-wavelength red and blue laser light. AB - Indoor horticulture offers a sensible solution for sustainable food production and is becoming increasingly widespread. However, it incurs high energy and cost due to the use of artificial lighting such as high-pressure sodium lamps, fluorescent light or increasingly, the light-emitting diodes (LEDs). The energy efficiency and light quality of currently available horticultural lighting is suboptimal, and therefore less than ideal for sustainable and cost-effective large-scale plant production. Here, we demonstrate the use of high-powered single wavelength lasers for indoor horticulture. They are highly energy-efficient and can be remotely guided to the site of plant growth, thus reducing on-site heat accumulation. Furthermore, laser beams can be tailored to match the absorption profiles of different plant species. We have developed a prototype laser growth chamber and demonstrate that plants grown under laser illumination can complete a full growth cycle from seed to seed with phenotypes resembling those of plants grown under LEDs reported previously. Importantly, the plants have lower expression of proteins diagnostic for light and radiation stress. The phenotypical, biochemical and proteome data show that the single-wavelength laser light is suitable for plant growth and therefore, potentially able to unlock the advantages of this next generation lighting technology for highly energy efficient horticulture. PMID- 27659910 TI - Female hypospadias presenting with urinary retention and renal failure in an adolescent: uncommon and late presentation with significant hidden morbidity. AB - An 11-year-old girl presented with poor urinary stream with vaginal voiding since childhood. She had palpable bladder and raised serum creatinine (671 umol/L). Suprapubic catheterisation was performed after a failed urethral attempt. Following catheterisation she improved symptomatically. She underwent cystoscopy through the suprapubic portal as a guide wire could be negotiated through bladder neck; external urethral meatus was found as a dimple higher up in anterior vaginal wall. Female hypospadias is usually an incidental diagnosis during catheterisation for various reasons. Diagnosis could be established only after antegrade cystoscopy. Anecdotal cases have been reported in the literature with similar presentation. Early diagnosis is essential as renal failure could be a late presentation if patients continue to void with stenosed meatus. Long-term follow-up is needed as these patients may need definitive management later on. PMID- 27659911 TI - Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. AB - Patients with end-stage renal disease present with a distinct challenge in oncology. Many anticancer drugs and their metabolites are excreted by the kidney, but data to guide dose and schedule adjustments in renal dialysis are scant. Pembrolizumab is an anti-programmed cell death protein 1 monoclonal antibody proven to be effective in patients with metastatic melanoma. It has demonstrated promising results and was granted US Food and Drug Administration (FDA) approval in September, 2014 for metastatic melanoma. It was additionally approved for patients with metastatic non-small cell lung cancer by the FDA in October, 2015. We present the first case, to the best of our knowledge, of a patient with metastatic melanoma successfully treated with pembrolizumab while on haemodialysis. PMID- 27659912 TI - Severe liver involvement in two patients with long-term history of fever: remember familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) is characterised by recurrent, self-limited fever attacks and serositis. Severe liver involvement has rarely been reported. We present two FMF cases of a 55-year-old man and a 20-year-old woman in whom the prevailing manifestations were recurrent unexplained episodes of anicteric hepatitis (man) and recurrent severe jaundice (woman). A long-term history of recurrent self-limited episodes of fever was also claimed in both. After exclusion of infectious, malignant, autoimmune, and liver and biliary diseases, a diagnosis of FMF as confirmed by molecular analysis was established. The patients started colchicine 1 mg/day with immediate resolution of symptoms. During follow up, no new episodes of fever and exacerbation of liver biochemical parameters have been recorded for 5 and 1 years. Physicians must keep FMF in mind in patients with recurrent episodes of unexplained severe liver impairment and fever and especially in regions like Mediterranean basin where hereditary periodic fever syndromes are common. PMID- 27659913 TI - Pharmacokinetic-guided dosing of factor VIII concentrate in a patient with haemophilia during renal transplantation. AB - A 29-year-old man with severe haemophilia A and end-stage renal disease underwent a renal transplantation. To prevent bleeding, patient was treated with replacement therapy using factor VIII (FVIII) concentrate, according to National guidelines. Bayesian analysis was performed by combining observed FVIII concentrations with a population pharmacokinetic (PK) model for patients with severe haemophilia A in a perioperative setting. Application of Bayesian analysis led to accurate prediction of observed concentrations after prescribing dosing advice. We believe that PK-guided dosing of factor concentrates is a valuable step towards further individualisation of treatment in patients with bleeding disorders, especially in those patients requiring precise targeting of coagulation factor levels due to high risk of either bleeding or thrombosis, as illustrated by this patient undergoing a major surgical procedure. PMID- 27659914 TI - Acute brainstem haemorrhage as a presenting feature of high-grade glioma. PMID- 27659915 TI - Preemptive Isolation Precautions of Patients at High Risk for Methicillin Resistant Staphylococcus aureus in Combination With Ultrarapid Polymerase Chain Reaction Screening as an Effective Tool for Infection Control. AB - This sequential nonrandomized intervention study investigated the role of preemptive isolation precautions plus ultrarapid polymerase chain reaction screening for methicillin-resistant Staphylococcus aureus (MRSA). Compared with no prophylactic isolation plus conventional microbiology MRSA screening, nosocomial MRSA colonization and total MRSA incidence per 10,000 patient days significantly decreased. Infect Control Hosp Epidemiol 2016;1489-1491. PMID- 27659916 TI - ERK-mediated phosphorylation of BIS regulates nuclear translocation of HSF1 under oxidative stress. AB - B-cell lymphoma (BCL)-2-interacting cell death suppressor (BIS) has diverse cellular functions depending on its binding partners. However, little is known about the effects of biochemical modification of BIS on its various activities under oxidative stress conditions. In this study, we showed that H2O2 reduced BIS mobility on SDS-polyacrylamide gels in a time-dependent manner via the activation of extracellular signaling-regulated kinase (ERK). The combined results of mass spectroscopy and computational prediction identified Thr285 and Ser289 in BIS as candidate residues for phosphorylation by ERK under oxidative stress conditions. Deletion of these sites resulted in a partial reduction in the H2O2-induced mobility shift relative to that of the wild-type BIS protein; overexpression of the deletion mutant sensitized A172 cells to H2O2-induced cell death without increasing the level of intracellular reactive oxygen species. Expression of the BIS deletion mutant decreased the level of heat shock protein (HSP) 70 mRNA following H2O2 treatment, which was accompanied by impaired nuclear translocation of heat shock transcription factor (HSF) 1. Co-immunoprecipitation assays revealed that the binding of wild-type BIS to HSF1 was decreased by oxidative stress, while the binding of the BIS deletion mutant to HSF1 was not affected. These results indicate that ERK-dependent phosphorylation of BIS has a role in the regulation of nuclear translocation of HSF1 likely through modulation of its interaction affinity with HSF1, which affects HSP70 expression and sensitivity to oxidative stress. PMID- 27659917 TI - Sexual dysfunction in Klinefelter's syndrome patients. AB - Klinefelter's syndrome (KS) is the most common chromosomal abnormality in men with infertility and hypogonadism. Although its influence on fertility has been extensively investigated, very few studies assessed the sexual function of patients with KS. Our aim was to assess the prevalence of sexual dysfunction in patients with KS and investigate possible aetiological factors for reported findings. Medical records of 53 patients with KS were retrospectively reviewed and compared to 75 age-matched control subjects who were prospectively recruited. Sexual history was evaluated through utilisation of international index of erectile function-5 and Arabic index for premature ejaculation questionnaires. Sexual desire was reported subjectively by patients or controls. The incidence of erectile dysfunction and premature ejaculation in patients with KS was 18.9% and 22.6% respectively. Compared to age-matched controls, patients with KS had significantly lower incidence of PE. However, there was no statistically significant difference between both groups regarding erectile function. Libido was significantly lower in patients with KS than normal controls (54.7% vs. 17.3%, p = 0.001). Klinefelter's syndrome is a condition that has a variable presentation. Despite having a higher likelihood of reduced sexual desire, patients may have normal erectile function comparable to age-matched individuals. They tend to have a lower incidence of premature ejaculation. PMID- 27659918 TI - A novel method for mapping village-scale outdoor resting microhabitats of the primary African malaria vector, Anopheles gambiae. AB - BACKGROUND: Knowledge of Anopheles resting habitats is needed to advance outdoor malaria vector control. This study presents a technique to map locations of resting habitats using high-resolution satellite imagery (world view 2) and probabilistic Dempster-Shafer (D-S) modelling, focused on a rural village in southern Mali, West Africa where field sampling was conducted to determine outdoor habitat preferences of Anopheles gambiae, the main vector in the study area. METHODS: A combination of supervised and manual image classification was used to derive an accurate land-cover map from the satellite image that provided classes (i.e., photosynthetically active vegetation, water bodies, wetlands, and buildings) suitable for habitat assessment. Linear fuzzy functions were applied to the different image classes to scale resting habitat covariates into a common data range (0-1) with fuzzy breakpoints parameterized experimentally through comparison with mosquito outdoor resting data. Fuzzy layers were entered into a Dempster-Shafer (D-S) weight-of-evidence model that produced pixel-based probability of resting habitat locations. RESULTS: The D-S model provided a highly detailed suitability map of resting locations. The results indicated a significant difference (p < 0.001) between D-S values at locations positive for An. gambiae and a set of randomly sampled points. Further, a negative binomial regression indicated that although the D-S estimates did not predict abundance (p > 0.05) subsequent analysis suggested that the D-S modelling approach may provide a reasonable estimate locations of low-to-medium An. gambiae density. These results suggest that that D-S modelling performed well in identifying presence points and specifically resting habitats. CONCLUSION: The use of a D-S modelling framework for predicting the outdoor resting habitat locations provided novel information on this little-known aspect of anopheline ecology. The technique used here may be applied more broadly at different geographic scales using Google Earth, Landsat or other remotely-sensed imagery to assess the malaria vector resting habitats where outdoor control measures can reduce the burden of the disease in Africa and elsewhere. PMID- 27659920 TI - Elected to the Leopoldina: R. Muller / Inhoffen Medal: T. Carell / Max Rossler Prize: C. Coperet / Miklos Bodanszky Award: M. Kohn / SPSJ International Award: T. P. Russell. PMID- 27659919 TI - Synchrotron imaging of dentition provides insights into the biology of Hesperornis and Ichthyornis, the "last" toothed birds. AB - BACKGROUND: The dentitions of extinct organisms can provide pivotal information regarding their phylogenetic position, as well as paleobiology, diet, development, and growth. Extant birds are edentulous (toothless), but their closest relatives among stem birds, the Cretaceous Hesperornithiformes and Ichthyornithiformes, retained teeth. Despite their significant phylogenetic position immediately outside the avian crown group, the dentitions of these taxa have never been studied in detail. To obtain new insight into the biology of these 'last' toothed birds, we use cutting-edge visualisation techniques to describe their dentitions at unprecedented levels of detail, in particular propagation phase contrast x-ray synchrotron microtomography at high-resolution. RESULTS: Among other characteristics of tooth shape, growth, attachment, implantation, replacement, and dental tissue microstructures, revealed by these analyses, we find that tooth morphology and ornamentation differ greatly between the Hesperornithiformes and Ichthyornithiformes. We also highlight the first Old World, and youngest record of the major Mesozoic clade Ichthyornithiformes. Both taxa exhibit extremely thin and simple enamel. The extension rate of Hesperornis tooth dentine appears relatively high compared to non-avian dinosaurs. Root attachment is found for the first time to be fully thecodont via gomphosis in both taxa, but in Hesperornis secondary evolution led to teeth implantation in a groove, at least locally without a periodontal ligament. Dental replacement is shown to be lingual via a resorption pit in the root, in both taxa. CONCLUSIONS: Our results allow comparison with other archosaurs and also mammals, with implications regarding dental character evolution across amniotes. Some dental features of the 'last' toothed birds can be interpreted as functional adaptations related to diet and mode of predation, while others appear to be products of their peculiar phylogenetic heritage. The autapomorphic Hesperornis groove might have favoured firmer root attachment. These observations highlight complexity in the evolutionary history of tooth reduction in the avian lineage and also clarify alleged avian dental characteristics in the frame of a long-standing debate on bird origins. Finally, new hypotheses emerge that will possibly be tested by further analyses of avian teeth, for instance regarding dental replacement rates, or simplification and thinning of enamel throughout the course of early avian evolution. PMID- 27659921 TI - Predicted structure of a Minus-C OBP from Batocera horsfieldi (Hope) suggests an intermediate structure in evolution of OBPs. AB - Odorant binding proteins (OBPs) transport hydrophobic odorants from the environment to odorant receptors and play an important role in specific recognition of volatiles. Here, we expressed and purified a minus-C OBP, BhorOBPm2, from Batocera horsfieldi, a major pest of Popolus, to determine its binding characteristics with 58 candidate volatiles using a fluorescence competition-binding assay. We showed that BhorOBPm2 exhibited high binding affinity with chain volatiles and that ligands were selected based on chain length. In order to elucidate the binding mechanism, homology modeling and molecular-docking experiments were performed to investigate interactions between BhorOBPm2 and volatiles. The predicted structure with only two disulfide bonds showed one continuous channel for ligand binding, similar to classic OBPs AgamOBP1 and CquiOBP1. Unexpectedly, we observed a larger binding pocket for BhorOBPm2 and broader specificity for ligands than classic OBPs due to the expansive flexibility of BhorOBPm2 resulting from a lack of disulfide bonds. These findings suggested that BhorOBPm2 might present an intermediate structure in the evolution of OBPs. Furthermore, we designed two mutant proteins to simulate and verify functions of the C-terminal region. The changes in binding affinity observed here indicated a novel action differing from that of the "lid" described in previous studies. PMID- 27659922 TI - Cardiac magnetic resonance imaging: a new tool to identify cardioaortic sources in ischaemic stroke. AB - Stroke of undetermined aetiology or 'cryptogenic' stroke accounts for 30-40% of ischaemic strokes despite extensive diagnostic evaluation. The role and yield of cardiac imaging is controversial. Cardiac MRI (CMR) has been used for cardiac disorders, but its use in cryptogenic stroke is not well established. We reviewed the literature (randomised trials, exploratory comparative studies and case series) on the use of CMR in the diagnostic evaluation of patients with ischaemic stroke. The literature on the use of CMR in the diagnostic evaluation of ischaemic stroke is sparse. However, studies have demonstrated a potential role for CMR in the diagnostic evaluation of patients with cryptogenic stroke to identify potential aetiologies such as cardiac thrombi, cardiac tumours, aortic arch disease and other rare cardiac anomalies. CMR can also provide data on certain functional and structural parameters of the left atrium and the left atrial appendage which have been shown to be associated with ischaemic stroke risk. CMR is a non-invasive modality that can help identify potential mechanisms in cryptogenic stroke and patients who may be targeted for enrolment into clinical trials comparing anticoagulation to antiplatelet therapy in secondary stroke prevention. Prospective studies are needed to compare the value of CMR as compared to transthoracic and transesophageal echocardiography in the diagnostic evaluation of cryptogenic stroke. PMID- 27659923 TI - Cognitive outcome after ventral capsule/ventral striatum stimulation for treatment-resistant major depression. AB - BACKGROUND: We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS). METHODS: Participants were randomised to active (n=12) versus sham (n=13) DBS for 16 weeks. Data were analysed at the individual and group levels. Group differences were analysed using repeated measures ANOVAs. Relationships between depression severity and cognition were examined using partial correlations. The false discovery rate method controlled for multiple analyses. RESULTS: No significant interactions comparing active versus sham stimulation over time were evident. Change in depression was unrelated to change in neuropsychological measures. Twenty patients declined by >=1 SD on at least one measure (41.3% of declines occurred in active group participants; 63.0% in older participants regardless of stimulation status). Twenty-two patients exhibited improvements >1 SD on neuropsychological measures (47.7% in the active group; 63.1% in younger participants). CONCLUSIONS: These data suggest that VC/VS DBS in patients with TRD does not significantly affect neuropsychological function. Age at surgery, regardless of stimulation status, may be related to cognitive outcome at the individual patient level. TRIAL REGISTRATION NUMBER: NCT00837486; Results. PMID- 27659924 TI - The 2016 ISPD Update on Prevention and Treatment of Peritonitis-Grading the Evidence. PMID- 27659925 TI - Editors' Digest - Basic Science A Wearable Sweat Analyzer for Continuous Electrolyte Monitoring. PMID- 27659926 TI - Continuous Quality Improvement Initiatives to Sustainably Reduce Peritoneal Dialysis-Related Infections in Australia and New Zealand. PMID- 27659927 TI - Center-Centered in a Patient-Centered World? PMID- 27659928 TI - Percutaneous Endoscopic Gastrostomy with Jejunal Extension for an Encapsulating Peritoneal Sclerosis Refractory to Surgical Enterolysis. AB - Surgical enterolysis is the final option for patients with encapsulating peritoneal sclerosis (EPS). However, EPS is sometimes refractory to surgical enterolysis. This is the first report of successful use of percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) in a patient with EPS that was refractory to surgical enterolysis. We propose that sustained drainage of digestive juices by PEG-J, along with central venous nourishment at home, can be a treatment option for patients with EPS that cannot be treated with radical measures. PMID- 27659929 TI - Barriers to Peritoneal Dialysis in Saudi Arabia: Nephrologists' Perspectives. AB - In Saudi Arabia, only 9% of dialysis patients are on peritoneal dialysis (PD), and this has been the case for years. A number of centers around the world have sought to understand the underutilization of PD by asking nephrologists directly. In this study, we aimed to gather information that will answer the question "Why is PD underutilized in Saudi Arabia?" hoping that a roadmap may be developed to overcome the hurdles the study underscores, allowing for more patients to utilize this valuable modality. PMID- 27659930 TI - Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients. AB - Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated. PMID- 27659931 TI - Effect of balance Solution on the Peritoneal Membrane in Automated Peritoneal Dialysis. AB - Interference of conventional peritoneal dialysis fluids (cPDFs) with peritoneal membrane cell functions may be attributed to the dialysis fluid's low pH, high glucose concentration, and/or the presence of glucose degradation products (GDPs), the last of which leads to higher levels of advanced glycation end products (AGEs). It has been suggested that the peritoneal membrane might be better preserved by using biocompatible solutions, including cancer antigetn 125 (CA125). This prospective, open-label, multicentre, randomized, controlled, cross over phase IV study compared the in vivo biocompatibility of a neutral-pH, low GDP peritoneal dialysis (PD) solution (balance) with a cPDF in automated PD (APD) patients. Our study revealed a significantly increased appearance rate and concentration of CA125 in the peritoneal effluent of APD patients treated with the neutral-pH, low-GDP solution balance versus a conventional PD solution. PMID- 27659932 TI - Intraperitoneal Meropenem for Polymicrobial Peritoneal Dialysis-Related Peritonitis. AB - With the current rise in multiresistant gram-negative bacteria, carbapenems are more frequently used. Surprisingly, limited data exist on the pharmacokinetics of meropenem in peritoneal dialysis (PD)-related peritonitis. We report on the pharmacokinetics of repeated intraperitoneal (IP) meropenem during 21 days as treatment for polymicrobial multiresistent PD-related peritonitis.Our current report supports daily doses of 125 mg/L intraperitoneal meropenem in all bags as an effective and safe modality in the treatment of PD-associated peritonitis with multiresistant microorganisms. No signs of over- or underdosing were found based on serial drug concentration measurements at fixed time points up to 21 days. PMID- 27659933 TI - Shewanella algae Peritonitis in Patients on Peritoneal Dialysis. AB - Patients with peritonitis present with abdominal pain, diarrhea, fever, and turbid peritoneal dialysis (PD) fluid. Shewanella algae peritonitis has not yet been reported in PD patients in the literature. We present the first 2 cases of Shewanella algae peritonitis in PD patients. Mupirocin cream is applied on the exit site as prophylactic antibiotic therapy. PMID- 27659935 TI - A Rare Case of Roseomonas gilardii Peritonitis in a Patient on Continuous Ambulatory Peritoneal Dialysis. PMID- 27659934 TI - An Alternative Approach to Delivering Intensive Dialysis in Pregnancy. AB - Pregnancy outcomes in patients with end-stage renal disease (ESRD) on dialysis are improving. Recent literature supports intensive hemodialysis (HD) as the modality of choice during pregnancy in ESRD. We report the successful delivery of a healthy infant at full term in a patient with ESRD by supplementing peritoneal dialysis (PD) with intermittent HD to achieve adequate dialysis intensity. PMID- 27659936 TI - Hemodialysis Switch Improved Colonic Angiodysplasia in a Peritoneal Dialysis Patient. PMID- 27659938 TI - Direct identification of trypanosomatids by matrix-assisted laser desorption ionization-time of flight mass spectrometry (DIT MALDI-TOF MS). AB - Accurate and rapid determination of trypanosomatids is essential in epidemiological surveillance and therapeutic studies. Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) has been shown to be a useful and powerful technique to identify bacteria, fungi, metazoa and human intact cells with applications in clinical settings. Here, we developed and optimized a MALDI-TOF MS method to profile trypanosomatids. trypanosomatid cells were deposited on a MALDI target plate followed by addition of matrix solution. The plate was then subjected to MALDI-TOF MS measurement to create reference mass spectra library and unknown samples were identified by pattern matching using the BioTyper software tool. Several m/z peaks reproducibly and uniquely identified trypanosomatids species showing the potentials of direct identification of trypanosomatids by MALDI-TOF MS. Moreover, this method discriminated different life stages of Trypanosoma cruzi, epimastigote and bloodstream trypomastigote and Trypanosoma brucei, procyclic and bloodstream. T. cruzi Discrete Typing Units (DTUs) were also discriminated in three clades. However, it was not possible to achieve enough resolution and software-assisted identification at the strain level. Overall, this study shows the importance of MALDI-TOF MS for the direct identification of trypanosomatids and opens new avenues for mass spectrometry-based detection of parasites in biofluids. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27659939 TI - Hip Capsular Closure: A Biomechanical Analysis of Failure Torque. AB - BACKGROUND: Hip capsulotomy is routinely performed during arthroscopic surgery to achieve adequate exposure of the joint. Iatrogenic instability can result after hip arthroscopic surgery because of capsular insufficiency, which can be avoided with effective closure of the hip capsule. There is currently no consensus in the literature regarding the optimal quantity of sutures upon capsular closure to achieve maximal stability postoperatively. Purpose/Hypothesis: The purpose of this study was to determine the failure torques of 1-, 2-, and 3-suture constructs for hip capsular closure to resist external rotation and extension after standard anterosuperior interportal capsulotomy (12 to 3 o'clock). Additionally, the degree of external rotation at which the suture constructs failed was recorded. The null hypothesis of this study was that no significant differences with respect to the failure torque would be found between the 3 repair constructs. STUDY DESIGN: Controlled laboratory study. METHODS: Nine pairs (n = 18) of fresh-frozen human cadaveric hemipelvises underwent anterosuperior interportal capsulotomy, which were repaired with 1, 2, or 3 side-to-side sutures. Each hip was secured in a dynamic biaxial testing machine and underwent a cyclic external rotation preconditioning protocol, followed by external rotation to failure. RESULTS: The failure torque of the 1-suture hip capsular closure construct was significantly less than that of the 3-suture construct. The median failure torque for the 1-suture construct was 67.4 N.m (range, 47.4-73.6 N.m). The median failure torque was 85.7 N.m (range, 56.9-99.1 N.m) for the 2 suture construct and 91.7 N.m (range, 74.7-99.0 N.m) for the 3-suture construct. All 3 repair constructs exhibited a median 36 degrees (range, 22 degrees -64 degrees ) of external rotation at the failure torque. CONCLUSION: The most important finding of this study was that the 2- and 3-suture constructs resulted in comparable biomechanical failure torques when external rotation forces were applied to conventional hip capsulotomy in a cadaveric model. The 3-suture construct was significantly stronger than the 1-suture construct; however, there was not a significant difference between the 2- and 3-suture constructs. Additionally, all constructs failed at approximately 36 degrees of external rotation. CLINICAL RELEVANCE: Re-establishing the native anatomy of the hip capsule after hip arthroscopic surgery has been reported to result in improved outcomes and reduce the risk of iatrogenic instability. Therefore, adequate capsular closure is important to restore proper hip biomechanics, and postoperative precautions limiting external rotation should be utilized to protect the repair. PMID- 27659937 TI - PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells. AB - BACKGROUND: Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. METHODS: Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. RESULTS: PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP 2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was the predominant mode of cell death and no autophagic death was observed. CONCLUSIONS: Our study demonstrates for the first time that PARP-1 inhibition in combination with carbon ion synergistically decreases MMPs activity along with overall increase of TIMPs. These data open up the possibilities of improvement of carbon ion therapy with PARP-1 inhibition to control highly metastatic cancers. PMID- 27659940 TI - Association of genetic polymorphisms of de novo nucleotide biosynthesis with increased CHD susceptibility in the northern Chinese population. AB - Congenital heart disease (CHD) is one of most prevalent birth defects in the world. However, the underlying molecular mechanism(s) have not been fully understood. Here we report that increased CHD susceptibility is associated with genetic polymorphisms for de novo nucleotide biosynthesis in northern Chinese population, which has been reported with lower plasma folate levels. Nine tagSNPs of four genes (GART, ATIC, MTHFD1 and SHMT1) in de novo nucleotide biosynthesis were sequenced in 802 sporadic CHD patients and 1093 controls from two Han Chinese populations, located in north China (Shandong) and South China (Shanghai), respectively. Six SNPs were found to be significantly associated with CHDs or septation defects only in the Shandong population dataset, but none displayed significant association with any CHDs in the Shanghai population dataset as well as in the combined dataset. We also showed that the minor A allele of rs7279549 in GART reduced transcriptional activity and displayed lower affinity for unknown transcription factor(s), demonstrating the allele is a functional risk factor for CHD in Shandong population. Our study indicates that dysregulation of de novo nucleotide biosynthesis pathway may conditionally contribute to CHD pathogenesis in northern Chinese. PMID- 27659941 TI - Primary thermometry triad at 6 mK in mesoscopic circuits. AB - Quantum physics emerge and develop as temperature is reduced. Although mesoscopic electrical circuits constitute an outstanding platform to explore quantum behaviour, the challenge in cooling the electrons impedes their potential. The strong coupling of such micrometre-scale devices with the measurement lines, combined with the weak coupling to the substrate, makes them extremely difficult to thermalize below 10 mK and imposes in situ thermometers. Here we demonstrate electronic quantum transport at 6 mK in micrometre-scale mesoscopic circuits. The thermometry methods are established by the comparison of three in situ primary thermometers, each involving a different underlying physics. The employed combination of quantum shot noise, quantum back action of a resistive circuit and conductance oscillations of a single-electron transistor covers a remarkably broad spectrum of mesoscopic phenomena. The experiment, performed in vacuum using a standard cryogen-free dilution refrigerator, paves the way towards the sub millikelvin range with additional thermalization and refrigeration techniques. PMID- 27659942 TI - Severe Coagulation Disorder and Thrombocytopenia Associated with Tigecycline - Case Report and Review of Literature. AB - Herein, we report a 70-year-old male patient, with recurrent multiple hepatic abscesses, that was admitted to the internal medicine department for treatment of Carbapenem Resistant Escherichia Coli (CRE) bacteremia. The patient was treated with Tigecycline; few days later, he developed "Disseminated Intravascular Coagulation (DIC)" like coagulation study abnormality that seemed to be related to Tigecycline treatment. Upon discontinuing it, the DIC-like condition was resolved. Tigecycline should be considered as a possible etiological factor in patients with DIC-like, and this therapy should be withdrawn immediately in suspected cases. PMID- 27659944 TI - Cryopreservation of Kudoa septempunctata sporoplasm using commercial freezing media. AB - Cryopreservation methods for Kudoa septempunctata have not been established. This prevents an effective study of K. septempunctata, which cannot be artificially cultivated in the laboratory. In this study, we attempted to establish a cryopreservation method for K. septempunctata sporoplasm using Cellbanker(r) 1, a commercial preservation medium for mammalian cells. Spores were purified from the meat of Paralichthys olivaceus (olive flounder). These purified spores were suspended in Cellbanker(r) 1 and were stored at -80 degrees C for up to 16 months. Although the spores stored at -80 degrees C for 16 months were damaged, the sporoplasms maintained its amoeba-like indeterminate morphology, and their motility was well preserved. The viability of sporoplasms was variable among vials but was not below 70 %. In addition, the sporoplasms stored at -80 degrees C for 16 months could decrease the transepithelial electrical resistance of Caco 2 cells. These results indicate that this cryopreservation method using Cellbanker(r) 1 could preserve the viability and pathogenesis of K. septempunctata sporoplasm. PMID- 27659943 TI - IMNGS: A comprehensive open resource of processed 16S rRNA microbial profiles for ecology and diversity studies. AB - The SRA (Sequence Read Archive) serves as primary depository for massive amounts of Next Generation Sequencing data, and currently host over 100,000 16S rRNA gene amplicon-based microbial profiles from various host habitats and environments. This number is increasing rapidly and there is a dire need for approaches to utilize this pool of knowledge. Here we created IMNGS (Integrated Microbial Next Generation Sequencing), an innovative platform that uniformly and systematically screens for and processes all prokaryotic 16S rRNA gene amplicon datasets available in SRA and uses them to build sample-specific sequence databases and OTU-based profiles. Via a web interface, this integrative sequence resource can easily be queried by users. We show examples of how the approach allows testing the ecological importance of specific microorganisms in different hosts or ecosystems, and performing targeted diversity studies for selected taxonomic groups. The platform also offers a complete workflow for de novo analysis of users' own raw 16S rRNA gene amplicon datasets for the sake of comparison with existing data. IMNGS can be accessed at www.imngs.org. PMID- 27659945 TI - Fabrication of dual-sensitive keratin-based polymer hydrogels and their controllable release behaviors. AB - Using feather keratin (FK) as a biocompatible and inexpensive biopolymer, a kind of dual-sensitive keratin-based polymer hydrogel (FK/PNiPA/PIAc-Gel) with interpenetrating network structure was prepared by two-step polymerization of N isopropyl acrylamide (NiPA) and itaconic acid (IAc) in presence of crosslinker. After being characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy, its swelling behaviors and environmental sensitivity were investigated. The obtained biopolymer based hydrogel has good swelling and deswelling performance, and it is sensitive to pH value, temperature and salts of environment. Using anticancer drug, doxorubicin hydrochloride (Dox.HCl), and Bovine serum albumin (BSA) as different drug molecules, its release behaviors in different environment were investigated. It was found that the release behaviors of FK/PNiPA/PIAc-Gel were controllable via adjusting pH value or temperature of environment. The cumulative release of the anticancer drug (Dox.HCl) reached 93.3% within 16 h, and the cumulative release rate of macromolecular drug (BSA) got to 75.9% in 24 h. In summary, the keratin-based biopolymer hydrogel with interpenetrating network structure, pH-sensitivity and temperature sensitivity are potentially applied to sustain drug carrier and humid medicinal material in the biomedical field or clinical nursing field. PMID- 27659946 TI - Distal airway epithelial progenitor cells are radiosensitive to High-LET radiation. AB - Exposure to high-linear energy transfer (LET) radiation occurs in a variety of situations, including charged particle radiotherapy, radiological accidents, and space travel. However, the extent of normal tissue injury in the lungs following high-LET radiation exposure is unknown. Here we show that exposure to high-LET radiation led to a prolonged loss of in vitro colony forming ability by airway epithelial progenitor cells. Furthermore, exposure to high-LET radiation induced clonal expansion of a subset of progenitor cells in the distal airway epithelium. Clonal expansion following high-LET radiation exposure was correlated with elevated progenitor cell apoptosis, persistent gamma-H2AX foci, and defects in mitotic progression of distal airway progenitors. We discovered that the effects of high-LET radiation exposure on progenitor cells occur in a p53-dependent manner. These data show that high-LET radiation depletes the distal airway progenitor pool by inducing cell death and loss of progenitor function, leading to clonal expansion. Importantly, high-LET radiation induces greater long-term damage to normal lung tissue than the relative equivalent dose of low-LET gamma rays, which has implications in therapeutic development and risk assessment. PMID- 27659947 TI - Earlobe-like peritoneal appendage near the angle of His: a useful landmark for demarcating the lateral margin of the gastric cardia. AB - The gastric cardia-the small area around the cardiac orifice including the abdominal esophagus-is an important target area for abdominal and thoracic surgeries, especially for laparoscopic procedures. In this study of 28 cadavers, a peritoneal earlobe-like appendage near the angle of His was identified as a useful indicator of the lateral margin of the abdominal esophagus, which is otherwise obscure because the peritoneum continues to the diaphragm without definite demarcation of this margin. This structure, which appears equivalent to the epiploic appendages, was commonly found to be present (in 22/28, 78.6 % of the 28 cadavers) and was 4-21 mm * 6-40 mm * 1-4 mm in size, triangular, round, or leaf-like in shape, contained fat, and was on an imaginary line along which the lesser omentum adheres to the lesser curvature and continues to the diaphragm (18/22, 81.8 %). This indicator is associated with the lesser omentum and is part of the gastrophrenic ligament, and could serve as a useful indicator of the margin of the gastric cardia, thus aiding surgeons performing laparoscopic surgery in this region. PMID- 27659948 TI - Corrigendum: How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration. PMID- 27659949 TI - Survey of Redox-Active Moieties for Application in Multiplexed Electrochemical Biosensors. AB - Recent years have seen the development of a large number of electrochemical sandwich assays and reagentless biosensor architectures employing biomolecules modified via the attachment of a redox-active "reporter." Here we survey a large set of potential redox reporters in order to determine which exhibits the best long-duration stability in thiol-on-gold monolayer-based sensors and to identify reporter "sets" signaling at distinct, nonoverlapping redox potentials in support of multiplexing and error correcting ratiometric or differential measurement approaches. Specifically, we have characterized the performance of more than a dozen potential reporters that are, first, redox active within the potential window over which thiol-on-gold monolayers are reasonably stable and, second, are available commercially in forms that are readily conjugated to biomolecules or can be converted into such forms in one or two simple synthetic steps. To test each of these reporters we conjugated it to one terminus of a single-stranded DNA "probe" that was attached by its other terminus via a six-carbon thiol to a gold electrode to form an "E-DNA" sensor responsive to its complementary DNA target. We then measured the signaling properties of each sensor as well as its stability against repeated voltammetric scans and against deployment in and reuse from blood serum. Doing so we find that the performance of methylene blue-based, thiol on-gold sensors is unmatched; the near-quantitative stability of such sensors against repeated scanning in even very complex sample matrices is unparalleled. While more modest, the stability of sensors employing a handful of other reporters, including anthraquinone, Nile blue, and ferrrocene, is reasonable. Our work thus serves as both to highlight the exceptional properties of methylene blue as a redox reporter in such applications and as a cautionary tale-we wish to help other researchers avoid fruitless efforts to employ the many, seemingly promising and yet ultimately inadequate reporters we have investigated. Finally, we hope that our work also serves as an illustration of the pressing need for the further development of useful redox reporters. PMID- 27659950 TI - The Capacity of Cognitive Control Estimated from a Perceptual Decision Making Task. AB - Cognitive control refers to the processes that permit selection and prioritization of information processing in different cognitive domains to reach the capacity-limited conscious mind. Although previous studies have suggested that the capacity of cognitive control itself is limited, a direct quantification of this capacity has not been attempted. In this behavioral study, we manipulated the information rate of cognitive control by parametrically varying both the uncertainty of stimul measured as information entropy and the exposure time of the stimuli. We used the relationship between the participants' response accuracy and the information rate of cognitive control (in bits per second, bps) in the model fitting to estimate the capacity of cognitive control. We found that the capacity of cognitive control was approximately 3 to 4 bps, demonstrating that cognitive control as a higher-level function has a remarkably low capacity. This quantification of the capacity of cognitive control may have significant theoretical and clinical implications. PMID- 27659952 TI - The Role of ZnP2 Nanoclusters in the Vibrational Properties of Cd x Zn(1 - x)P2 Solid Solutions. AB - This study reports an analysis of the IR reflectance and Raman spectra of Cd x Zn(1 - x)P2 solid solutions. We have analyzed the effect of the doping of the CdP2 single crystal by the ZnP2 nanoclusters on the vibrational properties of studied samples: epsilon 0, epsilon inf, phonon frequencies, and strengths. These dependencies might be used as an alternative non-destructive way for the control of the Cd x Zn(1 - x)P2 composition. The obtained results show that variation of the concentration of ZnP2 nanoclusters opens a space to design the tailored material properties for the industrial applications. PMID- 27659951 TI - Engineering Crack Formation in Carbon Nanotube-Silver Nanoparticle Composite Films for Sensitive and Durable Piezoresistive Sensors. AB - We report highly sensitive and reliable strain sensors based on silver nanoparticle (AgNP) and carbon nanotube (CNT) composite thin films. The CNT/AgNP was prepared by a screen printing process using a mixture of a CNT paste and an AgNP ink. It is discovered that the sensitivity of such sensors are highly dependent on the crack formation in the composites. By altering the substrate use and the relative ratios of AgNPs and CNTs, the formation and propagation of cracks can be properly engineered, leading to piezoresistive strain sensors with enhanced sensitivity and robustness. PMID- 27659953 TI - Laser Ablated Carbon Nanodots for Light Emission. AB - The synthesis of fluorescent carbon dots-like nanostructures (CNDs) obtained through the laser ablation of a carbon solid target in liquid environment is reported. The ablation process was induced in acetone with laser pulses of 1064, 532, and 355 nm under different irradiation times. Close-spherical amorphous CNDs with sizes between 5 and 20 nm, whose abundance strongly depends on the ablation parameters were investigated using electron microscopy and was confirmed using absorption and emission spectroscopies. The pi- pi* electronic transition at 3.76 eV dominates the absorption for all the CNDs species synthesized under different irradiation conditions. The light emission is most efficient due to excitation at 3.54 eV with the photoluminescence intensity centered at 3.23 eV. The light emission from the CNDs is most efficient due to ablation at 355 nm. The emission wavelength of the CNDs can be tuned from the near-UV to the green wavelength region by controlling the ablation time and modifying the ablation and excitation laser wavelength. PMID- 27659956 TI - ? PMID- 27659957 TI - ? PMID- 27659955 TI - The healing effect of Pistacia lentiscus fruit oil on laser burn. AB - CONTEXT: Since antiquity, Pistacia lentiscus L. (Anacardiaceae) fruit oil (PLFO) has been used as a remedy for primary health care such as burn treatment. OBJECTIVE: This study assesses the healing effect of PLFO on CO2 laser fractional burn in a rat model. MATERIALS AND METHODS: The study was carried out on 18 adult male Wistar rats. A second-degree laser burn (wound area = 2.2 cm2) was inflicted in the dorsal region by the application of CO2 fractional laser within the following parameters; Energy level: 25 MJ and Depth level: 4. After applying laser, the rats were divided into three groups: the first was treated with saline solution, the second with a reference cream 'CYTOL BASIC(r)' (0.13 MUg/mm2) and the third with PLFO (0.52 MUL/mm2). All treatments were topically administered for eight days. The healing effect was assessed using macroscopic, histological and biochemical parameters. RESULTS: After eight days, the higher percentage of wound healing contraction was observed among the PLFO-treated group (100%) followed by the 'CYTOL BASIC(r)' treated group (61.36%) and untreated group (32.27%). During the treatment, the PLFO-treated group showed less erythema, less crusting/scabbing, higher general wound appearance scores and a high content of collagen (220.67 +/- 7.48 mg/g of tissue) than the other groups. DISCUSSION AND CONCLUSION: The current study has shown, for the first time, the healing effect of PLFO on CO2 laser fractional burn. Their wound healing effect could be attributed to their antimicrobial, anti-inflammatory and antioxidant effects. PMID- 27659954 TI - Divalent copper ion bound amyloid-beta(40) and amyloid-beta(42) alloforms are less preferred than divalent zinc ion bound amyloid-beta(40) and amyloid-beta(42) alloforms. AB - Divalent copper and zinc ions bind to the amyloid-beta(40) and amyloid-beta(42) alloforms and affect their structural stability as well as their chemical and physical properties. Current literature debates the impact of copper ions on amyloid-beta alloforms. Recently, we reported the structural and thermodynamic properties of apo amyloid-beta and divalent zinc ion bound amyloid-beta alloforms (see, Wise-Scira et al. in J Biol Inorg Chem 17:927-938, 2012 and Coskuner et al. in ACS Chem Neurosci 4: 310-320, 2013). In our search for understanding the impacts of transition metal ions on disordered amyloid-beta, we also developed and reported new potential functions using quantum mechanics, which are required for high-quality molecular dynamics simulations of divalent copper ion bound amyloid-beta alloforms (see, Wise and Coskuner in J Comput Chem 35:1278-1289, 2014). The structures and thermodynamic properties of the divalent copper ion bound amyloid-beta(40) and amyloid-beta(42) alloforms in an aqueous medium are studied. The secondary and tertiary structures of divalent copper ion bound amyloid-beta(40) and amyloid-beta(42) along with their thermodynamic properties including enthalpy, entropy, Gibbs free energy and potential of mean force surface are investigated. Results are compared to those for apo amyloid-beta and divalent zinc ion bound amyloid-beta alloforms. Results demonstrate that copper binding to Abeta alloforms is thermodynamically less preferred rather than zinc binding. Less compact structures of copper ion bound amyloid-beta alloforms possess reduced stability in comparison to zinc ion bound amyloid-beta alloforms. Cu(II) binding impacts the thermodynamic properties, secondary and tertiary structural properties of Abeta40 and Abeta42. PMID- 27659959 TI - ? PMID- 27659958 TI - ? PMID- 27659961 TI - Enhanced separation and analysis procedure reveals production of tri-acylated mannosylerythritol lipids by Pseudozyma aphidis. AB - Mannosylerythritol lipids (MELs) are one of the most promising biosurfactants because of their high fermentation yields (>100 g l-1) and during the last two decades they have gained a lot of attention due to their interesting self assembling properties and biological activities. In this study, MELs were produced by fed-batch bioreactor fermentation of rapeseed oil with Pseudozyma aphidis MUCL 27852. This high-level MEL-producing yeast secretes four conventional MEL structures, -A, -B, -C and -D, which differ in their degree of acetylation. During our research, unknown compounds synthesized by P. aphidis were detected by thin-layer chromatography. The unknown compounds were separated by flash chromatography and identified as tri-acylated MELs by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The third fatty acid chain on the tri-acylated MELs was positioned on the primary alcohol of the erythritol moiety and comprised long-chain acids, mainly oleic and linoleic acid, which are not found in conventional di-acylated MELs. Furthermore, the LC-MS analysis time of conventional MELs was reduced to almost one-third by switching from HPLC-MS/MS to ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Provided optimization of the fermentation yield, P. aphidis could be an interesting novel producer of tri-acylated MELs and, thereby expand the supply and applicability of biosurfactants. PMID- 27659962 TI - "Same Room, Safe Place". AB - There are many different professional stances on safe sleep and then there is the reality of caring for a newborn. There is a debate among professionals regarding safe sleep recommendations. The continum of recommendations vary from the American Academy of Pediatrics (AAP) Safe Sleep Guidelines to the bed-sharing recommendations from the Mother-Baby Behavioral Sleep Laboratory. The lack of consistent and uniform safe sleep recommendations from health professionals has been confusing for families but has more recently raised a real professional ethical dilemma. Despite years of focused safe sleep community education and interventions, sleep-related infant deaths are on the rise in many communities. This commentary calls for a united safe sleep message from all health professionals to improve health for mothers and infants most at-risk, "Same Room, Safe Place." PMID- 27659963 TI - Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway. AB - The blood-brain barrier (BBB) disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process. However, the signaling pathway concerning vasogenic edema formation has not been clarified. In the present study, status epilepticus (SE) resulted in vascular endothelial growth factor (VEGF) over-expression accompanied by loss of BBB integrity in the rat piriform cortex. Leptomycin B (LMB, an inhibitor of chromosome region maintenance 1) attenuated SE-induced vasogenic edema formation. This anti-edema effect of LMB was relevant to inhibitions of VEGF over-expression as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, SB202190 (a p38 MAPK inhibitor) ameliorated vasogenic edema and VEGF over-expression induced by SE. These findings indicate that p38 MAPK/VEGF signaling pathway may be involved in BBB disruption following SE. Thus, we suggest that p38 MAPK/VEGF axis may be one of therapeutic targets for vasogenic edema in various neurological diseases. PMID- 27659960 TI - Genetic switches and related tools for controlling gene expression and electrical outputs of Geobacter sulfurreducens. AB - Physiological studies and biotechnology applications of Geobacter species have been limited by a lack of genetic tools. Therefore, potential additional molecular strategies for controlling metabolism were explored. When the gene for citrate synthase, or acetyl-CoA transferase, was placed under the control of a LacI/IPTG regulator/inducer system, cells grew on acetate only in the presence of IPTG. The TetR/AT system could also be used to control citrate synthase gene expression and acetate metabolism. A strain that required IPTG for growth on D lactate was constructed by placing the gene for D-lactate dehydrogenase under the control of the LacI/IPTG system. D-Lactate served as an inducer in a strain in which a D-lactate responsive promoter and transcription repressor were used to control citrate synthase expression. Iron- and potassium-responsive systems were successfully incorporated to regulate citrate synthase expression and growth on acetate. Linking the appropriate degradation tags on the citrate synthase protein made it possible to control acetate metabolism with either the endogenous ClpXP or exogenous Lon protease and tag system. The ability to control current output from Geobacter biofilms and the construction of an AND logic gate for acetate metabolism suggested that the tools developed may be applicable for biosensor and biocomputing applications. PMID- 27659964 TI - Erythropoietin improves hypoxic-ischemic encephalopathy in neonatal rats after short-term anoxia by enhancing angiogenesis. AB - Erythropoietin (EPO) is important for angiogenesis after hypoxia/ischemia. In this study, we investigated whether recombinant human erythropoietin (rhEPO) can enhance angiogenesis, and promote cognitive function through vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE). RhEPO, selective VEGFR2 inhibitor (SU5416) or vehicle was administrated by intraperitoneal injection. The assessment for cognitive function begins on day 60 after anoxia. Vascular density in hippocampus and white matter damage within corpus callosum were examined on day 28 after anoxia. The expression of erythropoietin receptor (EPOR), VEGF, rapidly accelerated fibrosarcoma 1 (Raf1), and extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in hippocampus were evaluated on day 7 after anoxia. RhEPO-treated anoxia rats had better cognitive recovery, higher vascular density, and less white matter damage than in the vehicle anoxia rats. These protective effects associated with increased expression of EPOR, VEGF; and increased phosphorylation of Raf1 and ERK1/2. While this up-regulation, and changes in the histopathologic and functional outcomes were abolished by SU5416. Our data indicate that rhEPO can enhance angiogenesis, reduce white matter damage, and promote cognitive recovery through VEGF/VEGFR2 signaling pathway in anoxia rats. PMID- 27659965 TI - Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells. AB - The canonical Wnt signaling pathway plays an important role in embryogenesis, and the establishment of neurogenic niches. It is involved in proliferation and differentiation of neural progenitors, since elevated Wnt/beta-catenin signaling promotes differentiation of neural stem/progenitor cells (NS/PCs1) towards neuroblasts. Nevertheless, it remains elusive how the differentiation program of neural progenitors is influenced by the Wnt signaling output. Using transgenic mouse models, we found that in vitro activation of Wnt signaling resulted in higher expression of beta-catenin protein and Wnt/beta-catenin target genes, while Wnt signaling inhibition resulted in the reverse effect. Within differentiated cells, we identified three electrophysiologically and immunocytochemically distinct cell types, whose incidence was markedly affected by the Wnt signaling output. Activation of the pathway suppressed gliogenesis, and promoted differentiation of NS/PCs towards a neuronal phenotype, while its inhibition led to suppressed neurogenesis and increased counts of cells of glial phenotype. Moreover, Wnt signaling hyperactivation resulted in an increased incidence of cells expressing outwardly rectifying K+ currents, together with inwardly rectifying Na+ currents, a typical current pattern of immature neurons, while blocking the pathway led to the opposite effect. Taken together, our data indicate that the Wnt signaling pathway orchestrates neonatal NS/PCs differentiation towards cells with neuronal characteristics, which might be important for nervous tissue regeneration during central nervous system disorders. Furthermore, the transgenic mouse strains used in this study may serve as a convenient tool to manipulate beta-catenin-dependent signaling in neural progenitors in the neonatal brain. PMID- 27659967 TI - Short-term effects of low-volume resuscitation with hypertonic saline and hydroxyethylstarch in an experimental model of lung contusion and haemorrhagic shock. AB - OBJECTIVES: This study aimed to assess the short-term respiratory tolerance and haemodynamic efficiency of low-volume resuscitation with hypertonic saline and hydroxyethylstarch (HS/HES) in a pig model of lung contusion and controlled haemorrhagic shock. We hypothesised that a low-volume of HS/HES after haemorrhagic shock did not impact contused lungs in terms of extravascular lung water 3hours after trauma. METHODS: A lung contusion resulting from blunt chest trauma was induced in 28 anaesthetised female pigs with five bolt-shots to the right thoracic cage, followed by haemorrhagic shock and fluid resuscitation. Pigs were randomly allocated into two groups: fluid resuscitation by 4ml/kg of HS/HES, or fluid resuscitation by 10ml/kg of normal saline (NS). Monitoring was based on transpulmonary thermodilution and a pulmonary artery catheter. After 3h, animals were euthanized to measure extravascular lung water (EVLW) by gravimetry. RESULTS: Blunt chest trauma was followed by a transient collapse and hypoxaemia in both groups. Post-mortem gravimetric assessment demonstrated a significant difference between EVLW in the NS-group (8.1+/-0.7ml/kg) and in the HS/HES-group (6.2+/-0.6ml/kg, P=0.038). Based on a pathological EVLW threshold of > 7ml/kg, results indicated that only the NS-group experienced moderate pulmonary oedema, contrary to the HS/HES-group. After haemorrhagic shock, HS/HES infusion enabled the restoration of effective mean arterial pressure and cardiac index. Intrapulmonary shunting increased transiently after fluid resuscitation but there was no significant impairment of oxygenation. CONCLUSION: In this pig model of lung contusion, the short-term assessment of fluid resuscitation after haemorrhagic shock with 4ml/kg of HS/HES showed that pulmonary oedema was avoided compared to fluid resuscitation with 10ml/kg of NS. PMID- 27659966 TI - Altered glutamate release in the dorsal striatum of the MitoPark mouse model of Parkinson's disease. AB - Mitochondrial dysfunction has been implicated in the degeneration of dopamine (DA) neurons in Parkinson's disease (PD). In addition, animal models of PD utilizing neurotoxins, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, have shown that these toxins disrupt mitochondrial respiration by targeting complex I of the electron transport chain, thereby impairing DA neurons in these models. A MitoPark mouse model was created to mimic the mitochondrial dysfunction observed in the DA system of PD patients. These mice display the same phenotypic characteristics as PD, including accelerated decline in motor function and DAergic systems with age. Previously, these mice have responded to L-Dopa treatment and develop L-Dopa induced dyskinesia (LID) as they age. A potential mechanism involved in the formation of LID is greater glutamate release into the dorsal striatum as a result of altered basal ganglia neurocircuitry due to reduced nigrostriatal DA neurotransmission. Therefore, the focus of this study was to assess various indicators of glutamate neurotransmission in the dorsal striatum of MitoPark mice at an age in which nigrostriatal DA has degenerated. At 28 weeks of age, MitoPark mice had, upon KCl stimulation, greater glutamate release in the dorsal striatum compared to control mice. In addition, uptake kinetics were slower in MitoPark mice. These findings were coupled with reduced expression of the glutamate re-uptake transporter, GLT 1, thus providing an environment suitable for glutamate excitotoxic events, leading to altered physiological function in these mice. PMID- 27659968 TI - Reduced variability and execution time to reach a target with a needle GPS system: Comparison between physicians, residents and nurse anaesthetists. AB - Ultrasound (US) guided needle positioning is safer than anatomical landmark techniques for central venous access. Hand-eye coordination and execution time depend on the professional's ability, previous training and personal skills. Needle guidance positioning systems (GPS) may theoretically reduce execution time and facilitate needle positioning in specific targets, thus improving patient comfort and safety. Three groups of healthcare professionals (41 anaesthesiologists and intensivists, 41 residents in anaesthesiology and intensive care, 39 nurse anaesthetists) were included and required to perform 3 tasks (positioning the tip of a needle in three different targets in a silicon phantom) by using successively a conventional US-guided needle positioning and a needle GPS. We measured execution times to perform the tasks, hand-eye coordination and the number of repositioning occurrences or errors in handling the needle or the probe. Without the GPS system, we observed a significant inter individual difference for execution time (P<0.05), hand-eye coordination and the number of errors/needle repositioning between physicians, residents and nurse anaesthetists. US training and video gaming were found to be independent factors associated with a shorter execution time. Use of GPS attenuated the inter individual and group variability. We observed a reduced execution time and improved hand-eye coordination in all groups as compared to US without GPS. Neither US training, video gaming nor demographic personal or professional factors were found to be significantly associated with reduced execution time when GPS was used. US associated with GPS systems may improve safety and decrease execution time by reducing inter-individual variability between professionals for needle-handling procedures. PMID- 27659969 TI - Management of direct oral anticoagulants in patients undergoing elective surgeries and invasive procedures: Updated guidelines from the French Working Group on Perioperative Hemostasis (GIHP) - September 2015. AB - Since 2011, data on patients exposed to direct oral anticoagulants (DOAs) while undergoing invasive procedures have accumulated. At the same time, an increased hemorrhagic risk during perioperative bridging anticoagulation without thrombotic risk reduction has been demonstrated. This has led the GIHP to update their guidelines published in 2011. For scheduled procedures at low bleeding risk, it is suggested that patients interrupt DOAs the night before irrespective of type of drug and to resume therapy six hours or more after the end of the invasive procedure. For invasive procedures at high bleeding risk, it is suggested to interrupt rivaroxaban, apixaban and edoxaban three days before. Dabigatran should be interrupted according to the renal function, four days and five days if creatinine clearance is higher than 50mL/min and between 30 and 50mL/min, respectively. For invasive procedures at very high bleeding risk such as intracranial neurosurgery or neuraxial anesthesia, longer interruption times are suggested. Finally, bridging with parenteral anticoagulation and measurement of DOA concentrations can no longer routinely be used. PMID- 27659970 TI - Mapping the Function of Polycomb Proteins. AB - Polycomb group (PcG) proteins are master regulators of proliferation and development that play essential roles in human pathologies including cancers. PcGs act as gatekeepers of cellular identity, maintaining repression of a multitude of target genes. However, these properties have only been recently uncovered thanks to technological advances, first of all chromatin immunoprecipitations (ChIP), that allowed a systematic characterization of the activity of these factors in an unbiased manner at a genome-wide level. Using PcG protein as example, this chapter introduces the readers to the use of chromatin analysis (ChIP assays and replication timing) and how to move these approaches to a level of genome-wide interpretation. PMID- 27659971 TI - Chromatin Immunoprecipitation. AB - Chromatin immunoprecipitation (ChIP) is a valuable method to investigate protein DNA interactions in vivo. Since its discovery it has been indispensable to identify binding sites and patterns of a variety of DNA-interacting proteins, such as transcription factors and regulators, modified histones, and epigenetic modifiers. The Polycomb repressors were the first proteins that have been mapped using this technique, which provided the mechanistic basis for the understanding of their biological function. Cross-linked (XChIP) or native (NChIP) chromatin from tissues or cultured cells is fragmented and the protein of interest is immunoprecipitated using a specific antibody. The co-precipitated DNA is then purified and subjected to analysis by region-specific PCR, DNA microarray (ChIP on-chip), or next-generation sequencing (ChIP-seq). The assay can therefore produce information about the localization of the analyzed protein at specific candidate loci or throughout the entire genome. In this chapter, we provide a detailed protocol of the basic standard ChIP assay and some remarks about variations. PMID- 27659972 TI - Chromatin Preparation and Chromatin Immuno-precipitation from Drosophila Embryos. AB - This protocol provides specific details on how to perform Chromatin immunoprecipitation (ChIP) from Drosophila embryos. ChIP allows the matching of proteins or histone modifications to specific genomic regions. Formaldehyde-cross linked chromatin is isolated and antibodies against the target of interest are used to determine whether the target is associated with a specific DNA sequence. This can be performed in spatial and temporal manner and it can provide information about the genome-wide localization of a given protein or histone modification if coupled with deep sequencing technology (ChIP-Seq). PMID- 27659973 TI - ChIP-seq Data Processing for PcG Proteins and Associated Histone Modifications. AB - Chromatin Immunoprecipitation followed by massively parallel DNA sequencing (ChIP sequencing) has emerged as an essential technique to study the genome-wide location of DNA- or chromatin-associated proteins, such as the Polycomb group (PcG) proteins. After being generated by the sequencer, raw ChIP-seq sequence reads need to be processed by a data analysis pipeline. Here we describe the computational steps required to process PcG ChIP-seq data, including alignment, peak calling, and downstream analysis. PMID- 27659974 TI - Analysis of Single-Locus Replication Timing in Asynchronous Cycling Cells. AB - In higher eucaryotes, not all the genome is replicated simultaneously: there are parts of the genome that replicate at the beginning of S-phase (early S-phase), others that are replicated later. In each cell, early replicating genomic regions are alternated to late-replicating regions. In general, eucaryotic genomes are organized into structural domains where genes showing the same epigenetic state replicate at the same time.Here, we will describe the protocol that we routinely used for the analysis of replication timing of specific loci in Drosophila embryonic cell lines (S2 and S3) based on BrdU labeling and FACS sorting of different S-phase fractions (early, mid, late) of asynchronous cycling cells. PMID- 27659975 TI - Noncoding RNA Interplay with the Genome. AB - The majority of our genome is transcribed to produce RNA molecules that are mostly noncoding. Among them, long noncoding RNAs (lncRNAs) are the most numerous and functionally versatile class.LncRNAs have emerged as key regulators of gene expression at multiple levels.This section describes bioinformatics aspects important for lncRNA discovery and molecular approaches to perform structure function characterization of this exciting class of regulatory molecules. PMID- 27659976 TI - RIP: RNA Immunoprecipitation. AB - The relevance of RNA-protein interactions in modulating mRNA and noncoding RNA function is increasingly appreciated and several methods have been recently developed to map them. The RNA immunoprecipitation (RIP) is a powerful method to study the physical association between individual proteins and RNA molecules in vivo. The basic principles of RIP are very similar to those of chromatin immunoprecipitation (ChIP), a largely used tool in the epigenetic field, but with some important caveats. The approach is based on the use of a specific antibody raised against the protein of interest to pull down the RNA-binding protein (RBP) and target-RNA complexes. Any RNA that is associated with this protein complex will also be isolated and can be further analyzed by polymerase chain reaction based methods, hybridization, or sequencing.Several variants of this technique exist and can be divided into two main classes: native and cross-linked RNA immunoprecipitation. The native RIP allows to reveal the identity of RNAs directly bound by the protein and their abundance in the immunoprecipitated sample, while cross-linked RIP leads to precisely map the direct and indirect binding site of the RBP of interest to the RNA molecule.In this chapter both the protocols applied to mammalian cells are described taking into account the caveats and considerations required for designing, performing, and interpreting the results of these experiments. PMID- 27659977 TI - Capture Hybridization Analysis of DNA Targets. AB - There are numerous recent cases where chromatin modifying complexes associate with long noncoding RNA (lncRNA), stoking interest in lncRNA genomic localization and associated proteins. Capture Hybridization Analysis of RNA Targets (CHART) uses complementary oligonucleotides to purify an RNA with its associated genomic DNA or proteins from formaldehyde cross-linked chromatin. Deep sequencing of the purified DNA fragments gives a comprehensive profile of the potential lncRNA biological targets in vivo. The combined identification of the genomic localization of RNA and its protein partners can directly inform hypotheses about RNA function, including recruitment of chromatin modifying complexes. Here, we provide a detailed protocol on how to design antisense capture oligos and perform CHART in tissue culture cells. PMID- 27659978 TI - Identification of RNA-Protein Interactions Through In Vitro RNA Pull-Down Assays. AB - Recent advances in next-generation sequencing have revealed that majority of the human genome is transcribed into long and short RNA (ncRNA) transcripts. Many ncRNAs function by interacting with proteins and forming regulatory complexes. RNA-protein interactions are vital in controlling core cellular processes like transcription and translation. Therefore identifying proteins that interact with ncRNAs is central to deciphering ncRNA functions. Here we describe an RNA-protein pull-down assay, which enables the identification of proteins that interact with an RNA under study. As an example we describe pull-down of proteins interacting with ncRNA XIST, which assists in the recruitment of the polycomb-repressive complex-2 (PRC2) and drives X-chromosomal inactivation. PMID- 27659979 TI - Understanding RNA-Chromatin Interactions Using Chromatin Isolation by RNA Purification (ChIRP). AB - ChIRP is a novel and easy-to-use technique for studying long noncoding RNA (lncRNA)-chromatin interactions. RNA and chromatin are cross-linked in vivo using formaldehyde or glutaraldehyde, and purified using biotinylated antisense oligonucleotides that hybridize to the target RNA. Co-precipitated DNA is then purified and analyzed by quantitative PCR (qPCR) or high-throughput sequencing. PMID- 27659980 TI - Analysis RNA-seq and Noncoding RNA. AB - RNA-Seq is an approach to transcriptome profiling that uses deep-sequencing technologies to detect and accurately quantify RNA molecules originating from a genome at a given moment in time. In recent years, the advent of RNA-Seq has facilitated genome-wide expression profiling, including the identification of novel and rare transcripts like noncoding RNAs and novel alternative splicing isoforms.Here, we describe the analytical steps required for the identification and characterization of noncoding RNAs starting from RNA-Seq raw samples, with a particular emphasis on long noncoding RNAs (lncRNAs). PMID- 27659981 TI - The Dynamics of Polycomb Complexes. AB - Polycomb complexes are essential regulators of embryonic and adult stem cells, highly conserved from flies to mammals. Traditionally, their study was based on biochemical and genetic approaches. More recently, the development of novel technologies and the improvement and standardization of existing ones has allowed to address previously unexplored aspects of Polycomb biology, such as dynamics and regulation. In this chapter, relevant researchers in the field discuss novel technologies aimed at dissecting the dynamics of Polycomb complexes in normal and pathological conditions. PMID- 27659982 TI - Fluorescence Resonance Energy Transfer Microscopy for Measuring Chromatin Complex Structure and Dynamics. AB - The Polycomb group (PcG) proteins form regulatory complexes that modify the chromatin structure and silence their target genes. Recent works have found that the composition of Polycomb complexes is highly dynamic. Defining the different protein components of each complex is fundamental for better understanding their biological functions. Fluorescent resonance energy transfer (FRET) is a powerful tool to measure protein-protein interactions, in nanometer order and in their native cellular environment. Here we describe the preparation and execution of a typical FRET experiment using CFP-tagged protein as donor and YFP-tagged protein as acceptor. We further show that FRET can be used in a competition assay to measure binding affinities of different components of the same chromatin complex. PMID- 27659983 TI - Analysis of Endogenous Protein Interactions of Polycomb Group of Proteins in Mouse Embryonic Stem Cells. AB - PRC1 complexes contain four core subunits: Pcgf, Phc, Ring1, and Cbx proteins. Interestingly, mammalian genomes have several paralogues for each subunit, which are differentially expressed depending on the cell type, differentiation program, and cellular stimuli. Therefore, identification and characterization of the specific architecture of different PRC1 complexes during cellular differentiation are essential to better understand the function and recruitment mechanism of PRC1 complexes. In this chapter we describe several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells. PMID- 27659984 TI - Determination of Polycomb Group of Protein Compartmentalization Through Chromatin Fractionation Procedure. AB - Epigenetic mechanisms modulate and maintain the transcriptional state of the genome acting at various levels on chromatin. Emerging findings suggest that the position in the nuclear space and the cross talk between components of the nuclear architecture play a role in the regulation of epigenetic signatures. We recently described a cross talk between the Polycomb group of proteins (PcG) epigenetic repressors and the nuclear lamina. This interplay is important for the maintenance of transcriptional repression at muscle-specific genes and for the correct timing of muscle differentiation. To investigate the synergism between PcG factors and nuclear architecture we improved a chromatin fractionation protocol with the aim to analyze the PcG nuclear compartmentalization. We thus separated PcG proteins in different fractions depending on their solubility. We surprisingly found a consistent amount of PcG proteins in the matrix-associated fraction. In this chapter we describe the chromatin fractionation procedure, a method that can be used to study the nuclear compartmentalization of Polycomb group of proteins and/or PcG targets in murine and Drosophila cells. PMID- 27659986 TI - Polymer Physics of the Large-Scale Structure of Chromatin. AB - We summarize the picture emerging from recently proposed models of polymer physics describing the general features of chromatin large scale spatial architecture, as revealed by microscopy and Hi-C experiments. PMID- 27659985 TI - An Automatic Segmentation Method Combining an Active Contour Model and a Classification Technique for Detecting Polycomb-group Proteinsin High-Throughput Microscopy Images. AB - The large amount of data generated in biological experiments that rely on advanced microscopy can be handled only with automated image analysis. Most analyses require a reliable cell image segmentation eventually capable of detecting subcellular structures.We present an automatic segmentation method to detect Polycomb group (PcG) proteins areas isolated from nuclei regions in high resolution fluorescent cell image stacks. It combines two segmentation algorithms that use an active contour model and a classification technique serving as a tool to better understand the subcellular three-dimensional distribution of PcG proteins in live cell image sequences. We obtained accurate results throughout several cell image datasets, coming from different cell types and corresponding to different fluorescent labels, without requiring elaborate adjustments to each dataset. PMID- 27659987 TI - Chromosome Conformation Capture in Drosophila. AB - Linear chromatin fiber is packed inside the nuclei as a complex three-dimensional structure, and the organization of the chromatin has important roles in the appropriate spatial and temporal regulation of gene expression. To understand how chromatin organizes inside nuclei, and how regulatory proteins physically interact with genes, chromosome conformation capture (3C) technique provides a powerful and sensitive tool to detect both short- and long-range DNA-DNA interaction. Here I describe the 3C technique to detect the DNA-DNA interactions mediated by insulator proteins that are closely related to PcG in Drosophila, which is also broadly applicable to other systems. PMID- 27659988 TI - Chromosome Conformation Capture in Primary Human Cells. AB - 3D organization of the genome, its structural and regulatory function of cell identity, is acquiring prominent features in epigenetics studies; more efforts have been done to develop techniques that allow studying nuclear structure. Chromosome conformation capture (3C) has been set up in 2002 from Dekker and from that moment great investments were made to develop genomics variants of 3C technology (4C, 5C, Hi-C) providing new tools to investigate the shape of the genome in a more systematic and unbiased manner. 3C method allows scientists to fix dynamic and variable 3D interactions in nuclear space, and consequently to study which sequences interact, how a gene is regulated by different and distant enhancer, or how a set of enhancer could regulate transcriptional units; to follow the conformation that mediates regulation change in development; and to evaluate if this fine epigenetic mechanism is impaired in disease condition. PMID- 27659989 TI - Determination of High-Resolution 3D Chromatin Organization Using Circular Chromosome Conformation Capture (4C-seq). AB - 3D chromatin organization is essential for many aspects of transcriptional regulation. Circular Chromosome Conformation Capture followed by Illumina sequencing (4C-seq) is among the most powerful techniques to determine 3D chromatin organization. 4C-seq, like other modifications of the original 3C technique, uses the principle of "proximity ligation" to identify and quantify ten thousands of genomic interactions at a kilobase scale in a single experiment for predefined loci in the genome.In this chapter we focus on the experimental steps in the 4C-seq protocol, providing detailed descriptions on the preparation of cells, the construction of the circularized 3C library and the generation of the Illumina high throughput sequencing library. This protocol is particularly suited for the use of mammalian tissue samples, but can be used with minimal changes on circulating cells and cell lines from other sources as well. In the final section of this chapter, we provide a brief overview of data analysis approaches, accompanied by links to publicly available analysis tools. PMID- 27659990 TI - Chromosome Conformation Capture on Chip (4C): Data Processing. AB - 4C methods are useful to investigate dependencies between regulatory mechanisms and chromatin structures by revealing the frequency of chromatin contacts between a locus of interest and remote sequences on the chromosome. In this chapter we describe a protocol for the data analysis of microarray-based 4C experiments, presenting updated versions of the methods we used in a previous study of the large-scale chromatin interaction profile of a Polycomb response element in Drosophila. The protocol covers data preparation, normalization, microarray probe selection, and the multi-resolution detection of regions with enriched chromatin contacts. A reanalysis of two independent mouse datasets illustrates the versatility of this protocol and the importance of data processing in 4C. Methods were implemented in the R package MRA.TA (Multi-Resolution Analyses on Tiling Array data), and they can be used to analyze ChIP-on-chip data on broadly distributed chromatin components such as histone marks. PMID- 27659991 TI - In Vivo Models to Address the Function of Polycomb Group Proteins. AB - Initially discovered as repressors of homeotic gene expression in Drosophila, Polycomb group (PcG) proteins have now been shown to be involved in a plethora of biological processes. Indeed, by repressing a large number of target genes, including specific lineage genes, these chromatin factors play major roles in a multitude of cellular functions, such as pluripotency, differentiation, reprogramming, tissue regeneration, and nuclear organization. In this book chapter are presented in vivo approaches and technologies, which have been used in both mammalian and Drosophila systems to study the cellular functions of Polycomb group proteins. PMID- 27659992 TI - A Rapid TALEN Assembly Protocol. AB - Owing to their modular and highly specific DNA recognition mode, transcription activator-like effector nucleases (TALENs) have been rapidly adopted by the scientific community for the purpose of generating site-specific double-strand breaks (DSBs) on a DNA molecule. A pair of TALENs can be used to produce random insertions or deletions of various lengths via nonhomologous end-joining or together with a homologous donor DNA to induce precise sequence alterations by homologous recombination (HR). Here, we describe a method for TALEN assembly (easyT) and a strategy for genome engineering via HR. PMID- 27659993 TI - Following the Motion of Polycomb Bodies in Living Drosophila Embryos. AB - During the last two decades, observation of cell nuclei in live microscopy evidences motion of nuclear compartments. Drosophila embryos constitute a good model to study nuclear dynamic during cell differentiation because they can easily be observed in live microscopy. Inside the cell nucleus, Polycomb group proteins accumulate in foci named Pc bodies. Here, we describe a method to visualize and analyze the motion of these nuclear compartments inside cell nuclei of Drosophila embryos. PMID- 27659994 TI - Reprogramming of Somatic Cells Towards Pluripotency by Cell Fusion. AB - Pluripotent reprogramming can be dominantly induced in a somatic nucleus upon fusion with a pluripotent cell such as embryonic stem (ES) cell. Cell fusion between ES cells and somatic cells results in the formation of heterokaryons, in which the somatic nuclei begin to acquire features of the pluripotent partner. The generation of interspecies heterokaryons between mouse ES- and human somatic cells allows an experimenter to distinguish the nuclear events occurring specifically within the reprogrammed nucleus. Therefore, cell fusion provides a simple and rapid approach to look at the early nuclear events underlying pluripotent reprogramming. Here, we describe a polyethylene glycol (PEG)-mediated cell fusion protocol to generate interspecies heterokaryons and intraspecies hybrids between ES cells and B lymphocytes or fibroblasts. PMID- 27659995 TI - Imaginal Disc Transplantation in Drosophila. AB - Since Ephrussi and Beadle introduced imaginal disc transplantation to Drosophila research in 1936, the method played an important part towards a better understanding of disc patterning, tissue regeneration, and reprogramming phenomena like transdetermination. Despite increasing usage of high-throughput approaches towards solving biological problems this classical manual method is still in use for studying disc development in a semi-physiological context. Here we describe in detail a protocol and provide recommendations on the procedure in particular for analyzing the regenerative potential of imaginal disks. The steps consist of disc dissection and fragmentation, transplantation into the larval or adult abdomen, and the recovery of implants from the host abdomen. Additionally, we also describe how to make the special transplantation needle from a glass capillary. PMID- 27659996 TI - Isolation and Culture of Muscle Stem Cells. AB - Polycomb group (PcG) proteins are key epigenetic factors responsible for the proper spatiotemporal repression of defined transcriptional programs along the process of cell differentiation, including myogenesis. The discovery of the pivotal role played by PcG factors during myogenic differentiation relied on the possibility to culture myogenic cells in vitro. We describe here the methods currently used to isolate muscle stem cells (MuSCs) both from single myofibers and from bulk muscles by fluorescence-activated cell sorting (FACS), highlighting experimental details and critical steps. Through these techniques MuSCs can be efficiently isolated and cultured in vitro to recapitulate the different phases of myogenesis: activation, expansion, differentiation, and self-renewal. PMID- 27659998 TI - A scoping review of pediatric economic evaluation 1980-2014: do trends over time reflect changing priorities in evaluation methods and childhood disease? AB - INTRODUCTION: Economic evaluations conducted in children have unique features compared to adults. Important developments in pediatric economic evaluation in recent years include new options for valuing health states for cost-utility analysis (CUA) and shifting child health priorities. The Pediatric Economic Database Evaluation (PEDE) project includes a comprehensive database of pediatric health economic evaluations published since 1980. The objective of this scoping review was to identify trends over time in the use of CUA and other analytic techniques, and the therapeutic areas chosen for study. Areas covered: Medical and grey literature were searched, key characteristics were extracted, frequencies were tabulated and cross-tabulations were performed. Differences between early (1980 and 1999) and late (2000 and 2014) periods were assessed using a chi-squared statistic. Of the 2,776 pediatric economic evaluations published between 1980 and 2014, substantially more were cost-effectiveness analyses (CEAs) and CUAs than cost benefit analyses and cost minimization analyses (63.9 and 24.9% versus 7.6 and 3.6%, respectively). This pattern was consistent regardless of the type of intervention, disease or age group studied. A trend toward higher proportions of CUAs and CEAs was evident in the later period (X2 p < 0.0001). Other significant trends included a higher proportion of studies of preventive interventions (X2 p < 0.0001), and more studies in children aged 1 to 12 years and fewer in perinates in the later period (X2 p < 0.0001). Overall the most common disease class studied was infectious diseases (29.2%). Expert commentary: Pediatric economic evaluation continues to grow in volume and methodologic complexity. While CUAs have increased, whether their quality has improved remains unknown. Although most studies are in infectious disease, the volume of publications may not align with emerging child health priorities such as adolescent health, injury, developmental disabilities, mental health, and the use of personalized medicine. Increasing economic evaluations in these areas will enhance pediatric decision-making. PMID- 27659997 TI - Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy. AB - Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options. PMID- 27659999 TI - Performance of an Ultraviolet Mutagenetic Polyphosphate-Accumulating Bacterium PZ2 and Its Application for Wastewater Treatment in a Newly Designed Constructed Wetland. AB - Total phosphorus (TP) removal performance and application for wastewater treatment of polyphosphate-accumulating bacteria (PAB) in constructed wetlands (CWs) were investigated. In this study, a novel isolated ultraviolet (UV) mutant PZ2 with phosphate-accumulating ability was screened from domestic wastewater and identified as Pseudomonas putida by 16S ribosomal DNA (rDNA) sequencing analysis. The TP removal performance of PZ2 in the synthetic wastewater reached the highest of 93.95 % within 45 h. Two vertical subsurface flow CWs planted with two aquatic macrophytes Canna indica and Acorus calamus were newly designed. After inoculating PZ2 into two CWs within 45 h, the average chemical oxygen demand (COD), TP, and ammonia-nitrogen (NH3-N) removal efficiencies reached 68.50, 60.22, and 66.81 %, respectively. Vegetation type and filter size significantly influenced the TP removal capability of PZ2 in CWs. Meanwhile, considerable qualitative differences were found in the pollutant removal efficiencies of PZ2 with and without CWs in synthetic wastewater. These results could also indicate potential applications of the UV mutagenesis in PAB isolation and the newly designed CWs in wastewater treatments. PMID- 27660000 TI - Potential of Ca2+ in Mycobacterium tuberculosis H37Rv Pathogenesis and Survival. AB - The host-pathogen interaction and involvement of calcium (Ca2+) signaling in tuberculosis infection is crucial and plays a significant role in pathogenesis. Ca2+ is known as a ubiquitous second messenger that could control multiple processes and is included in cellular activities like division, motility, stress response, and signaling. However, Ca2+ is thought to be a regulative molecule in terms of TB infection but its binding relation with proteins/substrates molecules which are influenced with Ca2+ concentrations in host-pathogen interaction requires attention. So, in this review, our primary goal is to focus on some Ca2+ substrates/proteins and their imperative involvement in pathogenesis, which is unclear. We have discussed several Ca2+-binding substrate and protein that affect intracellular mechanism of infected host cell. The major involvement of these proteins/substrates including calmodulin (CaM), calpain, annexin, surfactant protein A (SP-A), surfactant protein D (SP-D), calprotectin (MRP8/14), and PE_PGRS family protein are considered to be significant; however, their detailed understanding in mycobacterium infection is limited. In this aspect, this study will help in adding up our understanding in TB biology and additionally in the development of new therapeutic approach to reduce TB pandemic worldwide. PMID- 27660002 TI - Increased Act1/IL-17R expression in Hirschsprung's disease. AB - PURPOSE: Hirschsprung's disease -associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Altered intestinal epithelial barrier function is implicated in the pathogenesis of HAEC. IL-17 is a proinflammatory cytokine that plays a crucial role in host defense against microbial organisms in the development of inflammatory diseases. Act1 is an essential adaptor molecule required for the IL-17-mediated inflammatory responses via interaction with IL-17 receptor (IL-17R). We designed this study to investigate the hypothesis that Act1/Il-17R expression is upregulated in HSCR. METHODS: We investigated Act1 and IL17R expression in ganglionic andaganglionic bowel of HD patients (n = 10) and controls (n = 10). qPCR, Western blotting and confocal immunofluorescence were performed. MAIN RESULTS: qPCR and Western blot analysis revealed that Act1 and IL17R are strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. Act1 and IL17R expression was significantly increased in HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a markedly increased expression of Act1 and IL17R in the colonic epithelium of patients with HSCR compared to controls. CONCLUSION: To our knowledge, we report, for the first time, the expression of Act1 in the human colon. The increased expression of Act1 and Il-17 in the aganglionic and ganglionic bowel in HSCR may result in IL-17-mediated increased inflammatory response leading to the development of HAEC. PMID- 27660003 TI - Two new prenylated isoflavones from Hedysarum multijugum. AB - Chemical investigation on the ethyl acetate extract of the roots of Hedysarum multijugum resulted in the isolation of two new prenylated isoflavonoids: 5, 7, 2'-trihydroxy-4'-methoxy-3'-(gamma, gamma-dimethylallyl) isoflavone (hedysarimisoflavone A, 1) and 5, 7, 2'-trihydroxy-4'-methoxy-6, 8-di-(gamma, gamma-dimethylallyl) isoflavone (hedysarimisoflavone B, 2). Their structures were elucidated on the basis of spectroscopic analyses, especially, 1H and 13C NMR spectra in conjunction with their 2D experiments, 1H-1H COSY, HMQC, HMBC, and NOESY. PMID- 27660004 TI - Implementation Science and Global Connectivity: HFSA's Path Forward. PMID- 27660005 TI - Metabolic coupling in pancreatic beta cells: lipolysis revisited. PMID- 27660007 TI - Worldwide prevalence of hypertension exceeds 1.3 billion. PMID- 27660006 TI - Identification of more objective biomarkers for Blood-Stasis syndrome diagnosis. AB - BACKGROUND: Blood-stasis syndrome (BSS) is one of the Traditional Chinese medicine (TCM) syndrome differentiations that are commonly seen in stroke and ischemic heart diseases; however, the BSS differentiation criterion is not standardized. More objective biomarkers for BSS diagnosis are needed. METHODS: Acute ischemic stroke (AIS) or unstable angina (UA) patients with BSS and healthy controls were enrolled. The miRNA and mRNA expression profiles of UA patients and AIS patients were compared to those of healthy controls to identify the differentially expressed miRNA and mRNA of BSS. Bioinformatics analysis was used to identify significantly deregulated miRNAs and mRNAs correlated to BSS. QRT-PCR was performed to validate the bioinformatics analysis results. RESULTS: Approximately 401 mRNAs and 11 miRNAs were differentially expressed in both UA and AIS patients compared to healthy controls. Gene ontology (GO) functional analysis was performed, and multiple GO terms were enriched. Among the overlapping DE miRNAs and mRNAs, miR-146b-5p, -199a-5p and 23 targeted mRNAs were pivotal genes in the BSS genomic characteristics. These 2 miRNAs and 23 mRNAs formed network-type biomarkers for BSS. CONCLUSIONS: The genomic characteristics of BSS were shown in this study. miR-146b-5p, -199a-5p and the 23 targeted mRNAs formed a diagnostic network for BSS. Further improvement and validation of this diagnostic network might lead to more objective diagnostic criteria for BSS. PMID- 27660008 TI - International collaborative study to establish the World Health Organization 2nd International Standard for Fibrinogen Concentrate (09/242): communication from the SSC of the ISTH. PMID- 27660009 TI - Kai-Xin-San, a standardized traditional Chinese medicine formula, up-regulates the expressions of synaptic proteins on hippocampus of chronic mild stress induced depressive rats and primary cultured rat hippocampal neuron. AB - BACKGROUND: Kai-xin-san (KXS), composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, is a famous Chinese medicinal formula applied for treating stress-related psychiatric disease with the symptoms such as depression, forgetfulness and dizziness. Dependent on the symptom differentiation of patients, the composition ratio of KXS was varied and one ratio of 3:2:2:3 was widely applied. However, its molecular mechanism has seldom been investigated. PURPOSE: We aimed to reveal the action mechanism of KXS on anti-depression on synaptic protein regulation in both in vivo and in vitro models. STUDY DESIGN/METHODS: Firstly, the anti-depression effect of KXS was evaluated on a chronic mild stress induced depressive animal model and the mRNA expressions of various synaptic proteins in hippocampus of the depressive rat brains were determined. Then, KXS with different ratios as well as single herb were further evaluated on rat primary cultured hippocampus neurons and the possible signaling pathway was explored. RESULTS: Intra-gastric administration of a chemically standardized KXS for only 6h significantly alleviated the CUMS-induced depressive symptoms displayed by enhanced sucrose consumption and this effect was maintained after daily treatment for seven days. Simultaneously, the mRNA expressions of various synaptic proteins in hippocampus were regulated. Among these synaptic proteins, synaptotagmin (pre-synaptic marker) and post synaptic density protein (post-synaptic marker), with the higher altered magnitude on animal model, were further evaluated on rat primary cultured hippocampus neurons. After neuronal cultures treated with three ratios of KXS at the early and late stages of its life episode, the expression levels of synaptotagmin and PSD95 were both enhanced dramatically via stimulating cAMP dependent pathway. However, different ratio exerted different efficacy. The ratio with higher amounts of Ginseng Radix et Rhizoma and Polygalae Radix showed better effect in early life episode while higher amounts of Acori Tatarinowii Rhizoma and Poria behaved better in late life episode. The contribution of single herb on expressions of synaptic proteins was also evaluated. CONCLUSIONS: KXS was beneficial for synaptogenesis by inducing synaptic protein expressions, which might account for its anti-depression effect. PMID- 27660010 TI - Therapeutic effect of Mahaenggamseok-tang on neutrophilic lung inflammation is associated with NF-kappaB suppression and Nrf2 activation. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mahaenggamseok-tang (MHGST), an herbal formula in traditional Asian medicine, has been used to treat patients with various pulmonary diseases including common cold and influenza. However, the potential therapeutic effect of MHGST on acute lung injury (ALI), a leading cause of death worldwide, and the anti-inflammatory mechanisms of MHGST remained less understood. MATERIALS AND METHODS: The methanol extract of MHGST was prepared and fingerprinted by HPLC. For the induction of ALI, C57BL/6 mice (n=5/group) received a single intraperitoneal (i.p.) injection of LPS. Referring to the dose for patients, two different amounts of MHGST were delivered in an aerosol to mouse lungs via trachea 2h after the i.p. LPS administration. Lung histology, bronchoalveolar lavage fluid, myeloperoxidase (MPO) activity, and the expression of inflammatory and Nrf2-dependent genes were analyzed to determine the effect of MHGST on lung inflammation. For mechanistic studies, western blotting and semi quantitative RT-PCR were conducted using RAW 264.7 cells. RESULTS: When administered 2h after the onset of ALI, MHGST relieved lung pathology characteristic to ALI, with decreases of neutrophil infiltration and MPO activity. While suppressing the expression of inflammatory genes, MHGST increased the expression of Nrf2-dependent genes in ALI mouse lungs. Concordantly, MHGST activated Nrf2 activity while suppressing NF-kappaB in RAW 264.7 cells. CONCLUSION: MHGST suppressed neutrophilic lung inflammation, a hallmark of ALI, which was associated with the activation of anti-inflammatory Nrf2 and the suppression of pro-inflammatory NF-kappaB. Our results suggest that MHGST has a therapeutic potential against ALI. PMID- 27660011 TI - Liujunzi Tang, a famous traditional Chinese medicine, ameliorates cigarette smoke induced mouse model of COPD. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Liujunzi Tang is a traditional herbal medicine widely used in East Asia and clinically applied to treat Phlegm-Heat Syndrome. The purpose of the present study was to investigate the protective effects of Liujunzi Tang on cigarette smoke-induced (CS) mouse model of chronic obstructive pulmonary disease (COPD) and explore its potential molecular mechanism. MATERIALS AND METHODS: The mice received 1h of cigarette smoke for 8 weeks. The serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL 6 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemical methods. Histopathological alteration was observed by hematoxylin-eosin (H&E) staining. Additionally, the expressions of nuclear transcription factor-kappaB (NF kappaBp65) and (inhibitor of NF-kappaB)IkappaB-alpha were determined by western blot and immunohistochemistry analysis. RESULTS: Liujunzi Tang enhanced the activities of antioxidant enzymes and attenuated the levels of lipid oxidative production, meanwhile significantly inhibited the generations of inflammatory cytokines by inhibiting the phosphorylation of IkappaB-alpha and NF-kappaB. CONCLUSION: Our findings indicated that Liujunzi Tang exhibited the protective effect on cigarette smoke-induced COPD mice by anti-inflammatory and anti oxidative properties through the inhibition of NF-kappaB activation. PMID- 27660012 TI - Gu-Ben-Fang-Xiao decoction attenuates sustained airway inflammation by suppressing ER stress response in a murine asthma remission model of respiratory syncytial virus infection. AB - ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous. Gubenfangxiao decoction (GBFXD) has been widely used in treating asthma remission stage for decades in the Jiangsu Province Hospital of Chinese Medicine, China. We previously demonstrated that GBFXD could downregulate the asthma susceptibility gene ORMDL3, a trigger of Endoplasmic reticulum (ER) stress and unfolded protein response (UPR). AIM THIS STUDY: To investigate the involvement of ER stress and UPR in the anti-inflammatory effects of GBFXD in Respiratory Syncytial Virus (RSV)-OVA-induced asthma remission mice. MATERIALS AND METHODS: Mice were orally administered GBFXD at three doses for 30 days after an RSV-OVA challenge. The levels of inflammation mediators in serum were measured using a Luminex assay and the amount of IFN-gamma in lung homogenates was detected using ELISA. The splenic CD4+ and CD8+ T lymphocytes were counted using flow cytometric analysis. The mRNA and protein levels of asthma susceptibility gene ORMDL3, ER stress markers (BIP, CHOP), and three canonical UPR branches (PERK-eIF2a-ATF4, IRE1alpha XBP1/IRE1alpha-JNK-AP1 and ATF6-SERCA2b signal pathways) were detected using real time RT-PCR and western blot. RESULTS: Histopathological analysis showed that the model group mice still exhibited a sustained airway inflammation even after suspending the OVA-challenge and RSV infections for 30 days. H&E staining results indicated that GBFXD could attenuate sustained airway inflammation. Decreased serum CXCL1 level and increased IFN-gamma level in lung homogenate were observed after GBFXD treatment. Reductions in the number of splenic CD4+/CD8+ T lymphocytes were found after DEX treatment. We further confirmed the previous finding that GBFXD could downregulate the expression of ORMDL3. As a result of suppressed UPR, decreased ER stress markers and inhibited UPR branches (PERK and IRE1alpha signal pathway) were also observed through the significant reduction of signature mRNA and protein expressions after GBFXD treatment. CONCLUSION: GBFXD can significantly attenuate RSV-OVA-induced persistent airway inflammation in murine asthma remission model. These effects may be mediated, at least partially, by inhibiting the activation of ER stress responses. PMID- 27660014 TI - Effect of vitamin E and selenium nanoparticles on post-thaw variables and oxidative status of rooster semen. AB - This study was conducted to determine the combined effects of adding vitamin E (VitE) and selenium nanoparticle (Nano-Se) as antioxidant supplements to rooster semen extender for freezing. Semen samples were collected from 12 White Leghorn roosters and pooled. Subsequently, the samples were divided into nine equal groups using modified Beltsville extender. Extenders were supplemented with either two amounts of VitE (5 and 10MUg/mL) or two amounts of Nano-Se (1% and 2%) or a combination of both VitE and Nano-Se, and no antioxidants extender (control group). Using 5MUg/mL VitE and 1% of Nano-Se improved (P<0.05) total sperm motility (79.28+/-3.86%), progressive sperm motility (18.03+/-1.02%), sperm viability (81.46+/-2.16%) and integrity of the sperm membrane (77.21+/-2.12%) after the freeze-thawing process compared with control group (54.08+/-3.86%, 10.96+/-1.02%, 60.53+/-2.16%, and 54.47+/-2.12%; respectively). Also, extenders supplemented with 5MUg/mL Vit E or 5MUg/mL VitE and 1% Nano-Se had a lesser malondialdehyde (MDA) concentration compared to control extender (1.15+/-0.32, and 1.29+/-0.32, respectively). Total abnormal morphology of sperm was decreased (P<0.05) by adding 5 or 10MUg/mL VitE alone or in combined with 1% or 2% Nano-Se. Moreover, extenders containing Nano-Se demonstrated greater glutathione peroxidase (GPx) activity compared to other extenders. Catalase (CAT) activity was greater in extender supplemented with 10MUg/mL VitE and 2% Nano-Se. Moreover, higher TAC was observed in extenders supplemented with VitE and Nano-Se. It can be concluded that addition of 5MUg/mL vitamin E in combined with 1% Nano-Se improved the post-thawing quality and oxidative variables of rooster semen. PMID- 27660013 TI - Anti-inflammatory activity of Barleria lupulina: Identification of active compounds that activate the Nrf2 cell defense pathway, organize cortical actin, reduce stress fibers, and improve cell junctions in microvascular endothelial cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Hot aqueous extracts of the plant Barleria lupulina (BL) are used for treating inflammatory conditions and diabetic vascular complications. AIM OF THE STUDY: The goal was to identify active compounds in hot aqueous extracts of BL (HAE-BL) that are consistent with a role in reducing inflammation and reducing the vascular pathology associated with diabetes. In particular, we examined activation of the Nrf2 cell defense pathway because our initial findings indicated that HAE-BL activates Nrf2, and because Nrf2 is known to suppress inflammation. Activation of Nrf2 by HAE-BL has not been described previously. MATERIALS AND METHODS: Human endothelial cells, real-time PCR, western blotting, cytoskeletal analyses, and assay-guided fractionation with HPLC were used to identify specific compounds in HAE-BL that activate the Nrf2 cell defense pathway and reduce markers of inflammation in vitro. RESULTS: HAE-BL potently activated the Nrf2 cell defense pathway in endothelial cells consistent with its traditional use and reported success in reducing inflammation. Assay guided fractionation with HPLC identified three alkyl catechols: 4-ethylcatechol, 4-vinylcatechol, and 4-methylcatechol, that are each potent Nrf2 activators. In addition to activating Nrf2, HAE-BL and akyl catechols each profoundly improved organization of the endothelial cell actin cytoskeleton, reduced actin stress fibers, organized cell-cell junctions, and induced expression of mRNA encoding claudin-5 that is important for formation of endothelial tight junctions and reducing vascular leak. CONCLUSIONS: HAE-BL contains important alkyl catechols that potently activate the Nrf2 cell defense pathway, improve organization of the endothelial cell cytoskeleton, and organize tight cell junctions. All of these properties are consistent with a role in reducing inflammation and reducing vascular leak. Because activation of the Nrf2 cell defense pathway also prevents cancers, neuro-degeneration, age-related macular degeneration, and also reduces the severity of chronic obstructive pulmonary disorder and multiple sclerosis, HAE-BL warrants additional consideration for these other serious disorders. PMID- 27660015 TI - A fully integrated electrochemical biosensor platform fabrication process for cytokines detection. AB - Interleukin-1b (IL-1b) and interleukin-10 (IL-10) biomarkers are one of many antigens that are secreted in acute stages of inflammation after left ventricle assisted device (LVAD) implantation for patients suffering from heart failure (HF). In the present study, we have developed a fully integrated electrochemical biosensor platform for cytokine detection at minute concentrations. Using eight gold working microelectrodes (WEs) the design will increase the sensitivity of detection, decrease the time of measurements, and allow a simultaneous detection of varying cytokine biomarkers. The biosensor platform was fabricated onto silicon substrates using silicon technology. Monoclonal antibodies (mAb) of anti human IL-1b and anti-human IL-10 were electroaddressed onto the gold WEs through functionalization with 4-carboxymethyl aryl diazonium (CMA). Cyclic voltammetry (CV) was applied during the WE functionalization process to characterize the gold WE surface properties. Finally, electrochemical impedance spectroscopy (EIS) characterized the modified gold WE. The biosensor platform was highly sensitive to the corresponding cytokines and no interference with other cytokines was observed. Both cytokines: IL-10 and IL-1b were detected within the range of 1pgmL 1 to 15pgmL-1. The present electrochemical biosensor platform is very promising for multi-detection of biomolecules which can dramatically decrease the time of analysis. This can provide data to clinicians and doctors concerning cytokines secretion at minute concentrations and the prediction of the first signs of inflammation after LVAD implantation. PMID- 27660016 TI - Highly sensitive Escherichia coli shear horizontal surface acoustic wave biosensor with silicon dioxide nanostructures. AB - Surface acoustic wave mediated transductions have been widely used in the sensors and actuators applications. In this study, a shear horizontal surface acoustic wave (SHSAW) was used for the detection of food pathogenic Escherichia coli O157:H7 (E.coli O157:H7), a dangerous strain among 225 E. coli unique serotypes. A few cells of this bacterium are able to cause young children to be most vulnerable to serious complications. Presence of higher than 1cfu E.coli O157:H7 in 25g of food has been considered as a dangerous level. The SHSAW biosensor was fabricated on 64 degrees YX LiNbO3 substrate. Its sensitivity was enhanced by depositing 130.5nm thin layer of SiO2 nanostructures with particle size lesser than 70nm. The nanostructures act both as a waveguide as well as a physical surface modification of the sensor prior to biomolecular immobilization. A specific DNA sequence from E. coli O157:H7 having 22 mers as an amine-terminated probe ssDNA was immobilized on the thin film sensing area through chemical functionalization [(CHO-(CH2)3-CHO) and APTES; NH2-(CH2)3-Si(OC2H5)3]. The high performance of sensor was shown with the specific oligonucleotide target and attained the sensitivity of 0.6439nM/0.1kHz and detection limit was down to 1.8femto-molar (1.8*10-15M). Further evidence was provided by specificity analysis using single mismatched and complementary oligonucleotide sequences. PMID- 27660017 TI - Corrigendum to 'A microfluidic device for the automated electrical readout of low density glass-slide microarrays' [Biosens. Bioelectron. 74 (2015) 698-704]. PMID- 27660018 TI - Sample-to-answer on molecular diagnosis of bacterial infection using integrated lab--on--a--disc. AB - Sepsis by bacterial infection causes high mortality in patients in intensive care unit (ICU). Rapid identification of bacterial infection is essential to ensure early appropriate administration of antibiotics to save lives of patients, yet the present benchtop molecular diagnosis is time-consuming and labor-intensive, which limits the treatment efficiency especially when the number of samples to be tested is extensive. Therefore, we hereby report a microfluidic platform lab-on-a disc (LOAD) to provide a sample-to-answer solution. Our LOAD customized design of microfluidic channels allows automation to mimic sequential analytical steps in benchtop environment. It relies on a simple but controllable centrifugation force for the actuation of samples and reagents. Our LOAD system performs three major functions, namely DNA extraction, isothermal DNA amplification and real-time signal detection, in a predefined sequence. The disc is self-contained for conducting sample heating with chemical lysis buffer and silica microbeads are employed for DNA extraction from clinical specimens. Molecular diagnosis of specific target bacteria DNA sequences is then performed using a real-time loop mediated isothermal amplification (RT-LAMP) with SYTO-9 as the signal reporter. Our LOAD system capable of bacterial identification of Mycobacterium tuberculosis (TB) and Acinetobacter baumanii (Ab) with the detection limits 103cfu/mL TB in sputum and 102cfu/mL Ab in blood within 2h after sample loading. The reported LOAD based on an integrated approach should address the growing needs for rapid point-of-care medical diagnosis in ICU. PMID- 27660019 TI - Improved DET communication between cellobiose dehydrogenase and a gold electrode modified with a rigid self-assembled monolayer and green metal nanoparticles: The role of an ordered nanostructuration. AB - Efficient direct electron transfer (DET) between cellobiose dehydrogenase from Corynascus thermophilus (CtCDH) and a novel gold electrode platform, obtained by covalent linking of green AuNPs and AgNPs modified with a dithiol self-assembled monolayer, consisting of biphenyl-4,4'-dithiol (BPDT), was presented. The green AuNPs and AgNPs were synthesized using quercetin as reducing agent at room temperature. TEM experiments showed that the AuNPs and AgNPs were circular in shape with an average diameter of 5 and 8nm, respectively. Cyclic voltammetry of CtCDH immobilized onto the AuNPs/BPDT/AuE and the AgNPs/BPDT/AuE electrode platforms were carried out and compared with naked AuE, BPDT/AuE, AuNPs/AuE, and AgNPs/AuE. A pair of well-defined redox waves in neutral pH solution due to efficient DET of CtCDH was present with both MNPs/BPDT/AuE platforms. No DET communication was found with platforms without MNPs linked to BPDT. The apparent heterogeneous electron transfer rate constants (kS) of CtCDH were calculated to be 21.5+/-0.8s-1 and 10.3+/-0.7s-1, for the AuNPs/BPDT/AuE and the AgNPs/BPDT/AuE platforms, respectively. The modified electrodes were successively used to develop an eco-friendly biosensor for lactose detection. The CtCDH/AuNPs/BPDT/AuE based biosensor showed the best analytical performances with an excellent stability, a detection limit of 3uM, a linear range between 5 and 400uM and a sensitivity of 27.5+/-2.5uAcm-2mM-1. Such performances were favorably compared with other lactose biosensors reported in literature. The biosensor was successively tested to quantify lactose content in real milk and cream samples. No significant interference present in the sample matrices was observed. PMID- 27660021 TI - Evaluation of available energy and total tract digestibility of acid-hydrolyzed ether extract of cottonseed oil for growing pigs by the difference and regression methods. AB - OBJECTIVE: The objective of this study was to determine the effect of inclusion level on the digestible energy (DE), metabolizable energy (ME), and total tract digestibility of acid-hydrolyzed ether extract (AEE) of cottonseed oil when fed to growing pigs. METHODS: Forty-two barrows (initial body weight = 35.51+/-2.01 kg) were randomly allotted to a completely randomized design with a corn-soybean meal basal diet, five levels of cottonseed oil (2%, 4%, 6%, 8%, and 10%) and a 10% soybean oil diet. Each diet was replicated six times with one pig per replicate. The experiment lasted 19 days, 7 d for cage adaptation, 7 d for diets adaptation and last 5 d for feces and urine collection. The energy values and apparent total tract digestibility (ATTD) of cottonseed oil and soybean oil were calculated by the difference method, and regression equations were established to predict the energy values of cottonseed oil. The apparent digested fat of the entire intestinal tract was also regressed against dietary fat intake to determine the true total tract digestibility (TTTD) and endogenous loss of fat for cottonseed oil. RESULTS: The results showed that the DE and ME contents of cottonseed oil were not different as the inclusion level increased. The DE and ME values determined by the regression equation were 36.28 MJ/kg and 34.96 MJ/kg, respectively, and the values were similar to the mean DE and ME values calculated by the difference method (36.18 and 35.56 MJ/kg, respectively). The ATTD of cottonseed oil was also not affected by the inclusion level of cottonseed oil, and the TTTD and EFL determined by the regression method were 92.40% and 13.83 g/kg of dry matter intake for corn-soybean basal diet. The DE, ME, and ATTD of AEE in soybean oil determined by the difference method were 35.70 MJ/kg, 35.20 MJ/kg and 92.31%, respectively. There were no differences in the DE, ME, and ATTD between cottonseed oil and soybean oil, although the ratio of unsaturated to saturated fatty acids for soybean oil was higher than for cottonseed oil. CONCLUSION: The DE, ME, and ATTD values of cottonseed oil were not affected by its dietary inclusion level. The energy values of cottonseed oil determined by the difference and regression methods were similar. Furthermore, the ratio of unsaturated to saturated fatty acid for oils was not the decisive factor to influence the energy values and ATTD of oils. PMID- 27660020 TI - Mammary alveolar cell as in vitro evaluation system for casein gene expression involved in glucose level. AB - OBJECTIVE: Glucose is an essential fuel in the energy metabolism and synthesis pathways of all mammalian cells. In lactating animals, glucose is the major precursor for lactose and is a substrate for the synthesis of milk proteins and fat in mammary secretory (alveolar) epithelial cells. However, clear utilization of glucose in mammary cells during lactogenesis is still unknown, due to the lack of in vitro analyzing models. Therefore, the objective of this study was to test the reliability of the mammary alveolar (MAC-T) cell as an in vitro study model for glucose metabolism and lactating system. METHODS: Undifferentiated MAC-T cells were cultured in three types of Dulbecco's modified Eagle's medium with varying levels of glucose (no-glucose: 0 g/L, low-glucose: 1 g/L, and high glucose: 4.5 g/L) for 8 d, after which differentiation to casein secretion was induced. Cell proliferation and expression levels of apoptotic genes, Insulin like growth factor-1 (IGF1) receptor, oxytocin receptor, alphaS1, alphaS2, and beta casein genes were analyzed at 1, 2, 4, and 8 d after differentiation. RESULTS: The proliferation of MAC-T cells with high-glucose treatment was seen to be significantly higher. Expression of apoptotic genes was not affected in any group. However, expression levels of the mammary development related gene (IGF1 receptor) and lactation related gene (oxytocin receptor) were significantly higher in the low-glucose group. Expressions of alphaS1-casein, alphaS2-casein, and beta-casein were also higher in the low-glucose treated group as compared to that in the no-glucose and high-glucose groups. CONCLUSION: The results demonstrated that although a high-glucose environment increases cell proliferation in MAC-T cells, a low-glucose treatment to MAC-T cells induces higher expression of casein genes. Our results suggest that the MAC-T cells may be used as an in vitro model to analyze mammary cell development and lactation connected with precise biological effects. PMID- 27660022 TI - Comparative effects of corn-based diet and phase-fed cassava-based diet on growth rate, carcass characteristics and lipid profile of meat-type ducks. AB - OBJECTIVE: This experiment was conducted to evaluate the effects of a corn- or cassava- based diet on the production of meat-type ducks. METHODS: Four hundred day-old ducks were used in this experiment. They were divided into five groups with each group replicated eight times. The ducks fed the corn-based diets served as the control group. The four other groups comprised different treatments, with each one given the cassava-based diet based on phase-feeding. Three treatments were fed the cassava-based diet from 16, 28, and 35 d; respectively up to 42 d of age and the other group was fed the cassava-based diet from 1 to 42 d of age. RESULTS: The results indicated that ducks on either the corn- or cassava-based diets were similar in growth during 1 to 9 d of age. However, toward 35 to 42 d, the cassava-diet produced a higher weight gain (p<0.05). The cassava-based diet was better than the corn-based diet at increasing the outer and inner breast weights at 28, 35, or 42 d (p<0.05). In contrast, the corn-based diet was better at increasing abdominal fat (p<0.05). The two diets did not differ in their effects on the serum triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein-cholesterol, very-low-density lipoprotein cholesterol, and liver cholesterol. The corn-based diet, however, caused a highly significantly greater level of liver triglyceride (p<0.01). CONCLUSION: The results of this study suggest that both the cassava- and corn- based diets are similar in their effect on meat-type ducks during the starter stage but toward the finisher stage, the cassava-based diet has a better influence on weight gain and carcass characteristics. PMID- 27660023 TI - Effects of ruminally degradable starch levels on performance, nitrogen balance, and nutrient digestibility in dairy cows fed low corn-based starch diets. AB - OBJECTIVE: This trial was performed to examine the effects of ruminally degradable starch (RDS) levels in total mixed ration (TMR) with low corn-based starch on the milk production, whole-tract nutrient digestibility and nitrogen balance in dairy cows. METHODS: Eight multiparous Holstein cows (body weight [BW]: 717+/-63 kg; days in milk [DIM]: 169+/-29) were assigned to a crossover design with two dietary treatments: a diet containing 62.3% ruminally degradable starch (% of total starch, low RDS) or 72.1% ruminally degradable starch (% of total starch, high RDS). Changes to the ruminally degradable levels were conducted by using either finely ground corn or steam-flaked corn as the starch component. RESULTS: The results showed that dry matter intake, milk yield and composition in dairy cows were not affected by dietary treatments. The concentration of milk urea nitrogen was lower for cows fed high RDS TMR than low RDS TMR. The whole-tract apparent digestibility of neutral detergent fiber, acid detergent fiber and crude protein decreased, and that of starch increased for cows fed high RDS TMR over those fed low RDS TMR, with no dietary effect on the whole-tract apparent digestibility of dry matter and organic matter. The proportion of urinary N excretion in N intake was lower and that of fecal N excretion in N intake was higher for cows fed high RDS TMR than those fed low RDS TMR. The N secretion in milk and the retention of N were not influenced by the dietary treatments. Total purine derivative was similar in cows fed high RDS TMR and low RDS TMR. Consequently, estimated microbial N flow to the duodenum was similar in cows fed high RDS TMR and low RDS TMR. CONCLUSION: Results of this study show that ruminally degradable starch levels can influence whole-tract nutrient digestibility and nitrogen balance in dairy cows fed low corn-based starch diets, with no influence on performance. PMID- 27660024 TI - The effect of calcium propionate on the ruminal bacterial community composition in finishing bulls. AB - OBJECTIVE: Manipulating the fermentation to improve the performance of the ruminant has attracted the attention of both farmers and animal scientists. Propionate salt supplementation in the diet could disturb the concentration of propionate and total volatile fatty acids in the rumen. This study was conducted to evaluate the effect of calcium propionate supplementation on the ruminal bacterial community composition in finishing bulls. METHODS: Eight finishing bulls were randomly assigned to control group (CONT) and calcium propionate supplementation (PROP) feeding group, with four head per group. The control group was fed normal the total mixed ration (TMR) finishing diet, and PROP group was fed TMR supplemented with 200 g/d calcium propionate. At the end of the 51-day feeding trial, all bulls were slaughtered and rumen fluid was collected from each of the animals. RESULTS: Propionate supplementation had no influence the rumen fermentation parameters (p>0.05). Ruminal bacterial community composition was analyzed by sequencing of hypervariable V3 regions of the 16S rRNA gene. The most abundant phyla were the Firmicutes (60.68%) and Bacteroidetes (23.67%), followed by Tenericutes (4.95%) and TM7 (3.39%). The predominant genera included Succiniclasticum (9.43%), Butyrivibrio (3.74%), Ruminococcus (3.46%) and Prevotella (2.86%). Bacterial community composition in the two groups were highly similar, except the abundance of Tenericutes declined along with the calcium propionate supplementation (p = 0.0078). CONCLUSION: These data suggest that the ruminal bacterial community composition is nearly unchanged by propionate supplementation in finishing bulls. PMID- 27660025 TI - Enrichment and verification of differentially expressed miRNAs in bursa of Fabricius in two breeds of duck. AB - OBJECTIVE: The bursa of Fabricius (BF) is a central humoral immune organ belonging specifically to avians. Recent studies had suggested that miRNAs were active regulators involved in the immune processes. This study was to investigate the possible differences of the BF at miRNA level between two genetically disparate duck breeds. METHODS: Using Illumina next-generation sequencing, the miRNAs libraries of ducks were established. RESULTS: The results showed that there were 66 differentially expressed miRNAs and 28 novel miRNAs in bursa. A set of abundant miRNAs (i.e., let-7, miR-146a-5p, miR-21-5p, miR-17~92) which are involved in immunity and disease were detected and the predicted target genes of the novel miRNAs were associated with duck high anti-adversity ability. By gene ontology analysis and enriching KEGG pathway, the targets of differential expressed miRNAs were mainly involved in immunity and disease, supporting that there were differences in the BF immune functions between the two duck breeds. In addition, the metabolic pathway had the maximum enriched target genes and some enriched pathways that were related to cell cycle, protein synthesis, cell proliferation and apoptosis. It indicted that the difference of metabolism may be one of the reasons leading the immune difference between the BF of two duck breeds. CONCLUSION: This data lists the main differences in the BF at miRNAs level between two genetically disparate duck breeds and lays a foundation to carry out molecular assisted breeding of poultry in the future. PMID- 27660026 TI - Antioxidant capacity of phytochemicals and their potential effects on oxidative status in animals - A review. AB - Oxidative stress suppresses animal health, performance, and production, subsequently impacting economic feasibility; hence, maintaining and improving oxidative status especially through natural nutrition strategy are essential for normal physiological process in animals. Phytochemicals are naturally occurring antioxidants that could be considered as one of the most promising materials used in animal diets in various forms. In this review, their antioxidant effects on animals are discussed as reflected by improved apparent performance, productivity, and the internal physiological changes. Moreover, the antioxidant actions toward animals further describe a molecular basis to elucidate their underlying mechanisms targeting signal transduction pathways, especially through the antioxidant response element/nuclear factor (erythroid-derived 2)-like 2 transcription system. PMID- 27660027 TI - Detection of Trichomonas vaginalis in prostate tissue and serostatus in patients with asymptomatic benign prostatic hyperplasia. AB - BACKGROUND: Despite a worldwide common and progressive nature of benign prostate hyperplasia (BPH) in older men, no association has been observed between a causative pathogen and other etiology so far. METHODS: In this study, we investigated a causative association of Trichomonas vaginalis, a flagellate protozoan parasite, in 171 BPH cases presenting without symptoms of prostatitis at a surgical outpatient clinic in Kuwait. We detected T. vaginalis DNA by polymerase chain reaction (PCR) and T. vaginalis antigen by immunocytochemistry (ICC) in the prostate tissue of these cases. A total of 171 age-matched controls with no urinary tract symptoms were also included in the study. A detailed information regarding the sexual history and sexually transmitted infections (STIs) was enquired from all the enrolled subjects. RESULTS: We detected T. vaginalis DNA and T. vaginalis antigen in 42 (24.6 %) and 37 (21.6 %) of the 171 BPH cases respectively in their prostate tissue. Both these assays showed a very good agreement and statistically no significant difference in their sensitivities and specificities. A relatively higher seropositivity rate for antibodies to T. vaginalis was detected in BPH cases (53 of 171 cases, 31.0 %) than in the control group (26.9 %) [p: 0.19] and both were higher than in earlier reports but no significant association was observed between BPH and T. vaginalis serostatus. However, a greater proportion of seroreactive BPH cases had high IgG2 antibody absorbance score than in the control group (p:0.000). Furthermore, no significant association was observed between T. vaginalis seropositivity and presence of T. vaginalis DNA in the prostate tissue. CONCLUSIONS: Our study documents T. vaginalis DNA and T. vaginalis antigen in 24.6 and 21.6 % respectively in the prostate tissue of the BPH cases. We also detected a relatively higher seropositivity rate for antibodies to T. vaginalis both in the BPH cases and in normal control group, 31 and 26.9 % respectively but no significant association was observed between BPH and T. vaginalis serostatus or presence of T. vaginalis DNA in the prostate tissue. Further epidemiological and case-controlled studies are needed to focus on local response to chronic asymptomatic retention of T. vaginalis in prostate tissue in the development of benign prostate hyperplasia. PMID- 27660029 TI - Imaging biomarker in liver transplantation (LT): Role of brain MRI on evaluation of early disappearance of basal ganglia hyperintensity after successful LT. PMID- 27660031 TI - Seven days in medicine: 14-20 September 2016. PMID- 27660028 TI - Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor. AB - Angiotensin-(1-5) [Ang-(1-5)], which is a metabolite of Angiotensin-(1-7) [Ang-(1 7)] catalyzed by angiotensin-converting enzyme (ACE), is a pentapeptide of the renin-angiotensin system (RAS). It has been reported that Ang-(1-7) and Ang-(1-9) stimulate the secretion of atrial natriuretic peptide (ANP) via Mas receptor (Mas R) and Ang II type 2 receptor (AT2R), respectively. However, it still remains unknown whether Ang-(1-5) has a similar function to Ang-(1-7). We investigated the effect of Ang-(1-5) on ANP secretion and to define its signaling pathway using isolated perfused beating rat atria. Ang-(1-5) (0.3, 3, 10MUM) stimulated high pacing frequency-induced ANP secretion in a dose-dependent manner. Ang-(1-5) induced ANP secretion (3MUM) was attenuated by the pretreatment with an antagonist of Mas R (A-779) but not by an antagonist of AT1R (losartan) or AT2R (PD123,319). An inhibitor for phosphatidylinositol 3-kinase (PI3K; wortmannin), protein kinase B (Akt; API-2), or nitric oxide synthase (NOS; L-NAME) also attenuated the augmentation of ANP secretion induced by Ang-(1-5). Ang-(1-5) induced ANP secretion was markedly attenuated in isoproterenol-treated hypertrophied atria. The secretagogue effect of Ang-(1-5) on ANP secretion was similar to those induced by Ang-(1-9) and Ang-(1-7). These results suggest that Ang-(1-5) is an active mediator of renin-angiotensin system to stimulate ANP secretion via Mas R and PI3K-Akt-NOS pathway. PMID- 27660030 TI - SERKing Coreceptors for Receptors. AB - Plants have evolved a large number of cell surface-resident receptor-like kinases (RLKs) and receptor-like proteins (RLPs), many of which are implicated in sensing extrinsic and intrinsic signals, and govern diverse cellular responses. The signaling pathways mediated by RLKs and RLPs converge at a small group of RLKs, somatic embryogenesis receptor kinases (SERKs), via ligand-induced heterodimerization and transphosphorylation. As shared coreceptors in diverse signaling receptorsomes, SERKs exhibit functional plasticity yet maintain a high degree of signaling specificity. Here, we review recent advances in newly identified SERK functions in plant cell differentiation, growth, and immunity; discuss the regulation and activation mechanisms of SERK-associated receptorsomes; and provide insights into how SERKs maintain signaling specificity as convergent hubs in various signaling pathways. PMID- 27660032 TI - Expectation and expectoration: Information manipulation alters spitting volume, a common proxy for salivary flow. AB - Saliva is becoming an increasingly useful research material across multiple fields of inquiry, including biomedical, dental, psychological, nutritional, and food choice research. However, both the flow rate and protein composition of stimulated saliva differ as a function of the collection method. We hypothesized that the context in which a stimulus is presented to participants may alter salivation via top down cognitive effects and/or behavioral changes (i.e., spitting efficiency). We presented participants with one stimulus (commercially available green tea) in two distinct contexts, once where the tea was described as a food item ("tea") and once where it was described as a disgusting non-food item ("rabbit hair extract"). Saliva and the expectorated stimulus were collected following 15s of oral exposure in a crossover design with the identical stimulus presented in both contexts; saliva was also collected for 5min after stimulation while chewing a piece of wax. Participants also completed validated personality instruments to measure food involvement, sensation seeking, sensitivity to reward, and sensitivity to punishment. Our data suggest participants spat out more sample when told they received the 'non-food' stimulus compared to the 'food' stimulus, particularly when they were given the non-food stimulus first. Further, individuals who were higher in sensation seeking spat out more sample during the 'food' condition compared to individuals with lower sensation seeking scores, but this difference was absent in the 'non-food' condition. While consistent with a top down cognitive effect on salivary flow, we believe a greater motivation to spit out the 'non-food' stimulus is a more likely explanation. In either case, it is clear the context in which a stimulus is presented alters how much sample/saliva is expectorated, suggesting context needs to be carefully considered in future work on salivary flow. PMID- 27660034 TI - Schisantherin B ameliorates Abeta1-42-induced cognitive decline via restoration of GLT-1 in a mouse model of Alzheimer's disease. AB - Accumulation of amyloid beta (Abeta) peptide and hyperphosphorylated tau protein has been proposed to play roles in neural destruction which induce Alzheimer's disease (AD) progresses, glutamate transporter type 1 (GLT-1) and Glycogen synthase kinase3beta (GSK3beta) may be the pathological links between Abeta and tau pathology. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on improving the cognitive function and neurodegeneration in the mouse model of Alzheimer's disease induced by Abeta1-42, and its possible mechanism were Glutamate transporter GLT-1, tau and GSK3beta. It was found that successive intracerebroventricular (ICV) administration of STB (0.15mg/kg) for 5days significantly attenuated Abeta1-42-induced learning and memory impairment as measured by the Locomotor activity test, Y-maze test and Morris water maze test. Furthermore, STB at a dose of 0.15mg/kg restored the activities of GLT-1 and GSK3beta while decreasing the levels of hyperphosphorylated tau protein in the hippocampus and cerebral cortex. The results suggested that STB might protect against cognitive deficits and neurodegeneration induced by Abeta1-42 in mice by regulating the GLT-1 restoration as well as the capacity of GSK3beta. PMID- 27660035 TI - Incremental change in the set of coactive cortical assemblies enables mental continuity. AB - This opinion article explores how sustained neural firing in association areas allows high-order mental representations to be coactivated over multiple perception-action cycles, permitting sequential mental states to share overlapping content and thus be recursively interrelated. The term "state spanning coactivity" (SSC) is introduced to refer to neural nodes that remain coactive as a group over a given period of time. SSC ensures that contextual groupings of goal or motor-relevant representations will demonstrate continuous activity over a delay period. It also allows potentially related representations to accumulate and coactivate despite delays between their initial appearances. The nodes that demonstrate SSC are a subset of the active representations from the previous state, and can act as referents to which newly introduced representations of succeeding states relate. Coactive nodes pool their spreading activity, converging on and activating new nodes, adding these to the remaining nodes from the previous state. Thus, the overall distribution of coactive nodes in cortical networks evolves gradually during contextual updating. The term "incremental change in state-spanning coactivity" (icSSC) is introduced to refer to this gradual evolution. Because a number of associated representations can be sustained continuously, each brain state is embedded recursively in the previous state, amounting to an iterative process that can implement learned algorithms to progress toward a complex result. The longer representations are sustained, the more successive mental states can share related content, exhibit progressive qualities, implement complex algorithms, and carry thematic or narrative continuity. Included is a discussion of the implications that SSC and icSSC may have for understanding working memory, defining consciousness, and constructing AI architectures. PMID- 27660033 TI - Associations among sugar sweetened beverage intake, visceral fat, and cortisol awakening response in minority youth. AB - CONTEXT: Abdominal adiposity has long been associated with excess caloric intake possibly resulting from increased psychosocial stress and associated cortisol dysfunction. However, the relationship of sugar-sweetened beverage (SSB) intake specifically with cortisol variability and visceral adipose tissue (VAT) is unknown. OBJECTIVE: To examine the relationships between SSB intake, VAT, and cortisol response in minority youth. DESIGN: A cross-sectional analysis. SETTING: The University of Southern California. PARTICIPANTS: 60 overweight/obese Non Hispanic Black and Hispanic adolescents ages 14-18years. MAIN OUTCOME MEASURES: VAT via Magnet Resonance Imaging (MRI), cortisol awakening response (CAR) via multiple salivary samples, and SSB intake via multiple 24-hour diet recalls. SSB intake was divided into the following: low SSB consumers (<1 servings per day), medium SSB consumers (>=1-<2 servings per day), high SSB consumers (>=2 servings per day). Analysis of covariance were run with VAT and CAR as dependent variables and SSB intake categories (independent variable) with the following a priori covariates: sex, Tanner stage, ethnicity, caloric intake, and body mass index. RESULTS: The high SSB intake group exhibited a 7% higher VAT compared to the low SSB intake group (beta=0.25, CI:(0.03, 0.33), p=0.02). CAR was associated with VAT (beta=0.31, CI:(0.01,0.23), p=0.02). The high SSB intake group exhibited 22% higher CAR compared to the low SSB intake group (beta=0.30, CI:(0.02,0.48), p=0.04). CONCLUSION: This is the first study exploring the relationship between SSB, VAT, and CAR. SSB consumption appears to be independently associated greater abdominal adiposity and higher morning cortisol variability in overweight and obese minority youth. This study highlights potential targets for interventions specifically to reduce SSB intake in a minority youth population. PMID- 27660036 TI - Involvement of school students in fights with weapons: prevalence and associated factors in Brazil. AB - BACKGROUND: Violence, as well as other behaviors, is often intensified during adolescence and early adulthood. The objective of this study is estimate the prevalence of Brazilian school students involvement in fights with weapons and to analyze the associated factors. METHODS: This is a cross-sectional study using data from the National School Student Health Survey conducted in 2012 with 9th grade elementary school students attending 2842 schools in all 27 Brazilian Federative Units. The outcome studied was involvement in fights with firearms and/or cold weapons in the 30 days prior to the interview. Poisson regression was used to estimate the prevalence ratios and 95 % confidence intervals (95 % CI). The analyses were stratified by sex. RESULTS: Fifty seven thousand and eighty nine female students and 52,015 male students were included; the prevalence of their involvement in fights with weapons was 7.2 (95 % CI 6.9-7.5) and 13.8 (95 % CI 13.4-14.3), respectively. In the adjusted analysis the factors associated with male student involvement in fights with weapons were: being older, working, having smoked a cigarette, consumed alcoholic beverages and illicit drugs recently, insomnia, not having any close friends, skipping classes without parental supervision, having suffered aggression from a family member, reporting feeling unsafe on the way to or from school and/or at school. The same associated factors were found among female students in addition to not living with their father and/or mother and having suffered bullying. There was no association with type of school in either sex. CONCLUSION: Involvement in fights with weapons was greater among older male students. Health-risk behaviors, mental health characteristics, parental supervision and context of violence also showed association with the outcomes. PMID- 27660038 TI - Asthma hospitalisations and air pollution. PMID- 27660039 TI - Recurrent Hemorrhagic Venous Infarctions Caused by Thrombosis of a Pontine Developmental Venous Anomaly and Protein S Mutation. AB - A 34-year-old man presented with an acute onset of upbeat nystagmus, slurred speech, and limb and truncal ataxias. The patient had a history of limb ataxia and gait disturbance previously treated as brainstem encephalitis with corticosteroids 3 years previously. Brain magnetic resonance imaging showed pontine developmental venous anomaly (DVA) and hemorrhagic infarction within the drainage territory of the DVA. Three months later, the patient exhibited recurrent limb ataxia, double vision, and numbness of the left side of the body. The brain magnetic resonance imaging revealed recurrent hemorrhagic venous infarction within the same territory of the pontine DVA. Laboratory tests disclosed a hypercoagulable state owing to a decrease of protein S activity despite the normal antigen level. Genetic testing indicated that the patient was a homozygous carrier of protein S Tokushima. The patient's severe disability remained unchanged in spite of treatment with anticoagulation therapy using warfarin. We propose that further research on hereditary coagulopathy be carried out in patients with recurrent episodes of DVA-related infarction. PMID- 27660037 TI - Immature monocytes contribute to cardiopulmonary bypass-induced acute lung injury by generating inflammatory descendants. AB - BACKGROUND: As immune regulatory and effector cells, monocytes play an important role in the blood-extracorporeal circuit contact-related acute lung injury in patients undergoing cardiopulmonary bypass (CPB). However, circulating monocytes are phenotypically and functionally heterogeneous, so we characterised how immature monocytes affect acute lung injury induced by CPB. METHODS: The identification and dynamic changes in monocyte subsets were monitored by flow cytometry in patients undergoing CPB and in a rat model of CPB. The differentiation and migration of monocyte subsets were explored by in vitro cultures and adoptive transfer in the CPB rat model. RESULTS: We observed a dramatic increase of two monocyte subsets in the peripheral blood of patients undergoing CPB, involving tumour necrosis factor (TNF)-alpha-producing, mature intermediate CD14highCD16+ monocytes and a novel immature CD14lowCD16- subset. The immature CD14lowCD16- monocytes possessed limited ability for TNF-alpha production, and failed to suppress T-cell proliferation mediated by T-cell receptor signalling. However, these immature cells were highly proliferative and could differentiate into TNF-alpha producing, mature CD14highCD16+ monocytes. In the rat model of CPB, we further demonstrated that CPB induced migration of immature monocytes into the lungs, either from the bone marrow or from the spleen. Moreover, we confirmed the hypothesis that immature subsets could contribute to CPB-induced acute lung injury by giving rise to TNF-alpha producing descendants. CONCLUSIONS: The immature CD14lowCD16- monocytes might contribute to blood-circuit contact-induced acute lung injury by generating TNF-alpha producing, mature monocytes. New strategies based on monocyte manipulation could be a promising therapeutic approach for minimising CPB-related lung injury. PMID- 27660041 TI - Persistence analysis of poliovirus on three different types of fomites. AB - AIMS: The goal of this study was to explore various models for describing viral persistence (infectivity) on fomites and identify the best fit models. METHODS AND RESULTS: The persistence of poliovirus over time was studied on three different fomite materials: steel, cotton and plastic. Known concentrations of poliovirus type 1 were applied to the surface coupons in an indoor environment for various lengths of time. Viruses were recovered from the surfaces by vortexing in phosphate buffer. Seven different mathematical models of relative persistence over time were fit to the data, and the preferred model for each surface was selected based on the Bayesian information criterion. CONCLUSIONS: While the preferred model varied by fomite type, the virus showed a rapid initial decay on all of the fomite types, followed by a transition to a more gradual decay after about 4-8 days. Estimates of the time for 99% reduction ranged from 81 h for plastic to 143 h for cotton. A 6 log reduction of recoverable infectivity of poliovirus did not occur during the 3-week duration of the experiment for any of the fomites. SIGNIFICANCE AND IMPACT OF THE STUDY: In protected indoor environments poliovirus can remain infective for weeks. The models identified by this study can be used in risk assessments to identify appropriate strategies for managing this risk. PMID- 27660040 TI - Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways. AB - Inhibition of mammalian target of rapamycin, mTOR, extends lifespan and reduces age-related disease. It is not known what role mTOR plays in the arterial aging phenotype or if mTOR inhibition by dietary rapamycin ameliorates age-related arterial dysfunction. To explore this, young (3.8 +/- 0.6 months) and old (30.3 +/- 0.2 months) male B6D2F1 mice were fed a rapamycin supplemented or control diet for 6-8 weeks. Although there were few other notable changes in animal characteristics after rapamycin treatment, we found that glucose tolerance improved in old mice, but was impaired in young mice, after rapamycin supplementation (both P < 0.05). Aging increased mTOR activation in arteries evidenced by elevated S6K phosphorylation (P < 0.01), and this was reversed after rapamycin treatment in old mice (P < 0.05). Aging was also associated with impaired endothelium-dependent dilation (EDD) in the carotid artery (P < 0.05). Rapamycin improved EDD in old mice (P < 0.05). Superoxide production and NADPH oxidase expression were higher in arteries from old compared to young mice (P < 0.05), and rapamycin normalized these (P < 0.05) to levels not different from young mice. Scavenging superoxide improved carotid artery EDD in untreated (P < 0.05), but not rapamycin-treated, old mice. While aging increased large artery stiffness evidenced by increased aortic pulse-wave velocity (PWV) (P < 0.01), rapamycin treatment reduced aortic PWV (P < 0.05) and collagen content (P < 0.05) in old mice. Aortic adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and expression of the cell cycle-related proteins PTEN and p27kip were increased with rapamycin treatment in old mice (all P < 0.05). Lastly, aging resulted in augmentation of the arterial senescence marker, p19 (P < 0.05), and this was ameliorated by rapamycin treatment (P < 0.05). These results demonstrate beneficial effects of rapamycin treatment on arterial function in old mice and suggest these improvements are associated with reduced oxidative stress, AMPK activation and increased expression of proteins involved in the control of the cell cycle. PMID- 27660044 TI - 'It's all about me!': Was that the patient speaking? PMID- 27660043 TI - Potential of Camellia sinensis proanthocyanidins-rich fraction for controlling malaria mosquito populations through disruption of larval development. AB - BACKGROUND: Anopheles arabiensis and A. gambiae (sensu stricto) are the most prolific Afrotropical malaria vectors. Population control efforts of these two vectors have been hampered by extremely diverse larval breeding sites and widespread resistance to currently available insecticides. Control of mosquito larval stages using bioactive compounds of plant origin has the potential to suppress vector populations leading to concomitant reduction in disease transmission rates. In this study, we evaluated the efficacy of Camellia sinensis crude leaf extract and its fraction against the larvae of A. arabiensis and A. gambiae (s.s.). METHODS: Late third/early fourth instar larvae (L3/L4) of A. arabiensis and A. gambiae (s.s.) were exposed to increasing doses of C. sinensis leaf extract and its active fraction for 72 h, with mortality rates recorded every 24 h in both control and test groups. Ultra performance liquid chromatography electron spray ionization quadruple time of flight coupled with mass spectrometry (UPLC/ESI-Qtof/MS) was used to determine the main active constituents in the fraction. RESULTS: The major bioactive chemical constituents in the C. sinensis leaf extract were identified to be proanthocyanidins. The extract significantly interfered with larval survival and adult emergence in both species (ANOVA, F (5,24) = 1435.92, P < 0.001). Additionally, larval exposure to crude extract at 250 ppm and 500 ppm for 24 h resulted in larval mortality rates of over 90 % in A. gambiae (s.s.) and 75 % in A. arabiensis. A relatively lower concentration of 100 ppm resulted in moderate mortality rates of < 50 % in both species, but induced growth disruption effects evident as abnormal larval-pupal intermediates and disrupted adult emergence. The estimated LC50 concentrations of the crude leaf extract against A. arabiensis and A. gambiae (s.s.) larvae at 24 h were 154.58 ppm (95 % CI: 152.37-158.22) and 117.15 ppm (95 % CI: 112.86-127.04), respectively. The bioactive polar fraction caused 100 % larval mortality in both vector species at 25 ppm. CONCLUSIONS: Our findings demonstrate the potential of green tea extract and its active constituents in disrupting mosquito larval development. This could contribute to the control of mosquito populations and improved management of malaria. PMID- 27660045 TI - Raman microspectroscopy for the development and screening of recombinant cell lines. PMID- 27660042 TI - A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance the T1 Mapping and ECV Standardization in cardiovascular magnetic resonance (T1MES) program. AB - BACKGROUND: T1 mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T1 mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. METHODS: A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T1 and T2 in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformite Europeene (CE) marking. RESULTS: The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T1 maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the B 1 field. T1 and T2 values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15-30 degrees C the short-T1 tubes were more stable with temperature than the long-T1 tubes. A batch of 69 phantoms was mass-produced with random sampling of ten of these showing coefficients of variations for T1 of 0.64 +/- 0.45 % and 0.49 +/- 0.34 % at 1.5 T and 3 T respectively. CONCLUSION: The T1MES program has developed a T1 mapping phantom to CE/FDA manufacturing standards. An initial 69 phantoms with a multi-vendor user manual are now being scanned fortnightly in centers worldwide. Future results will explore T1 mapping sequences, platform performance, stability and the potential for standardization. PMID- 27660046 TI - Validity of a stroke severity index for administrative claims data research: a retrospective cohort study. AB - BACKGROUND: Ascertaining stroke severity in claims data-based studies is difficult because clinical information is unavailable. We assessed the predictive validity of a claims-based stroke severity index (SSI) and determined whether it improves case-mix adjustment. METHODS: We analyzed patients with acute ischemic stroke (AIS) from hospital-based stroke registries linked with a nationwide claims database. We estimated the SSI according to patient claims data. Actual stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) and functional outcomes measured with the modified Rankin Scale (mRS) were retrieved from stroke registries. Predictive validity was tested by correlating SSI with mRS. Logistic regression models were used to predict mortality. RESULTS: The SSI correlated with mRS at 3 months (Spearman rho = 0.578; 95 % confidence interval [CI], 0.556-0.600), 6 months (rho = 0.551; 95 % CI, 0.528-0.574), and 1 year (rho = 0.532; 95 % CI 0.504-0.560). Mortality models with the SSI demonstrated superior discrimination to those without. The AUCs of models including the SSI and models with the NIHSS did not differ significantly. CONCLUSIONS: The SSI correlated with functional outcomes after AIS and improved the case-mix adjustment of mortality models. It can act as a valid proxy for stroke severity in claims data-based studies. PMID- 27660047 TI - Robots to assist daily activities: views of older adults with Alzheimer's disease and their caregivers. AB - BACKGROUND: Robots have the potential to both enable older adults with dementia to perform daily activities with greater independence, and provide support to caregivers. This study explored perspectives of older adults with Alzheimer's disease (AD) and their caregivers on robots that provide stepwise prompting to complete activities in the home. METHODS: Ten dyads participated: Older adults with mild-to-moderate AD and difficulty completing activity steps, and their family caregivers. Older adults were prompted by a tele-operated robot to wash their hands in the bathroom and make a cup of tea in the kitchen. Caregivers observed interactions. Semi-structured interviews were conducted individually. Transcribed interviews were thematically analyzed. RESULTS: Three themes summarized responses to robot interactions: contemplating a future with assistive robots, considering opportunities with assistive robots, and reflecting on implications for social relationships. Older adults expressed opportunities for robots to help in daily activities, were open to the idea of robotic assistance, but did not want a robot. Caregivers identified numerous opportunities and were more open to robots. Several wanted a robot, if available. Positive consequences of robots in caregiving scenarios could include decreased frustration, stress, and relationship strain, and increased social interaction via the robot. A negative consequence could be decreased interaction with caregivers. CONCLUSIONS: Few studies have investigated in-depth perspectives of older adults with dementia and their caregivers following direct interaction with an assistive prompting robot. To fulfill the potential of robots, continued dialogue between users and developers, and consideration of robot design and caregiving relationship factors are necessary. PMID- 27660048 TI - Colour stabilities of three types of orthodontic clear aligners exposed to staining agents. AB - The aim of this study was to evaluate and compare the colour stabilities of three types of orthodontic clear aligners exposed to staining agents in vitro. Sixty clear orthodontic aligners produced by three manufacturers (Invisalign, Angelalign, and Smartee) were immersed in three staining solutions (coffee, black tea, and red wine) and one control solution (distilled water). After 12-h and 7 day immersions, the aligners were washed in an ultrasonic cleaner and measured with a colourimeter. The colour changes (DeltaE*) were calculated on the basis of the Commission Internationale de I'Eclairage L*a*b* colour system (CIE L*a*b*), and the results were then converted into National Bureau of Standards (NBS) units. Fourier transformation infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were conducted to observe the molecular and morphologic alterations to the aligner surfaces, respectively. The three types of aligners exhibited slight colour changes after 12 h of staining, with the exception of the Invisalign aligners stained with coffee. The Invisalign aligners exhibited significantly higher DeltaE* values (ranging from 0.30 to 27.81) than those of the Angelalign and Smartee aligners (DeltaE* values ranging from 0.33 to 1.89 and 0.32 to 1.61, respectively, P<0.05). FT-IR analysis confirmed that the polymer based structure of aligners did not exhibit significant chemical differences before and after the immersions. The SEM results revealed different surface alterations to the three types of aligner materials after the 7-day staining. The three types of aesthetic orthodontic appliances exhibited colour stability after the 12-h immersion, with the exception of the Invisalign aligners stained by coffee. The Invisalign aligners were more prone than the Angelalign and Smartee aligners to pigmentation. Aligner materials may be improved by considering aesthetic colour stability properties. PMID- 27660049 TI - The association between seminal vesicle size and duration of abstinence from ejaculation. AB - There are few data describing the relationship between seminal vesicle (SV) size and duration of abstinence between ejaculations. This study evaluates the association between SV size and duration of abstinence from ejaculation using pelvic magnetic resonance imaging (MRI). Sexually active men 18-68 years old who underwent pelvic MRI for various medical indications were included. The date of last ejaculation was recorded, and the cross-sectional areas of the right and left seminal vesicles were calculated separately using mediolateral and anteroposterior measurements on T2-weighted MRI images. The association between SV area and duration of abstinence between ejaculations was determined via linear regression analysis. The study cohort consisted of 104 men with a mean age of 46.45 +/- 11.4 (range 18-68) years old. Mean right and left SV cross-sectional areas were 744.1 +/- 351.1 (range: 149.9-1794.7) mm2 and 727.6 +/- 359.2 (range 171.4-2248.4) mm2 respectively. The mean duration of abstinence between ejaculations in the cohort was 3.6 +/- 2.6 (range 1-15) days. Although no correlation between age and SV area was observed (r = .007, p = .947), linear regression analysis demonstrated a positive correlation between SV area and the duration of abstinence from ejaculation (r = .372, p = .0001). SV cross-sectional area increases with duration of abstinence from ejaculation and can be assessed using MRI. The use of SV size estimation may be applicable in diagnosis, risk stratification and treatment of urological diseases. PMID- 27660050 TI - Sensorimotor Network Crucial for Inferring Amusement from Smiles. AB - Understanding whether another's smile reflects authentic amusement is a key challenge in social life, yet, the neural bases of this ability have been largely unexplored. Here, we combined transcranial magnetic stimulation (TMS) with a novel empathic accuracy (EA) task to test whether sensorimotor and mentalizing networks are critical for understanding another's amusement. Participants were presented with dynamic displays of smiles and explicitly requested to infer whether the smiling individual was feeling authentic amusement or not. TMS over sensorimotor regions representing the face (i.e., in the inferior frontal gyrus (IFG) and ventral primary somatosensory cortex (SI)), disrupted the ability to infer amusement authenticity from observed smiles. The same stimulation did not affect performance on a nonsocial task requiring participants to track the smiling expression but not to infer amusement. Neither TMS over prefrontal and temporo-parietal areas supporting mentalizing, nor peripheral control stimulations, affected performance on either task. Thus, motor and somatosensory circuits for controlling and sensing facial movements are causally essential for inferring amusement from another's smile. These findings highlight the functional relevance of IFG and SI to amusement understanding and suggest that EA abilities may be grounded in sensorimotor networks for moving and feeling the body. PMID- 27660052 TI - C14orf132 gene is possibly related to extremely low birth weight. AB - BACKGROUND: Despite extensive research the genetic component of extremely low birth weight (ELBW) in newborns has remained obscure. RESULTS: The aim of the case study was to identify candidate gene(s) causing ELBW in newborns and hypotrophy in infants. A family of four was studied: mother, father and two ELBW phenotype children. Studies were made of the medical conditions of the second child at birth and post-partum - peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy and suspected metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate the genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene - C14orf132 (chromosome 14 open reading frame 132) differentially expressed, with the level of the transcript significantly lower in the blood samples of the children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. CONCLUSION: We demonstrated the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the pre- and early postnatal developmental delay through the altered gene expression. PMID- 27660051 TI - Quantitative, model-based estimates of variability in the generation and serial intervals of Plasmodium falciparum malaria. AB - BACKGROUND: The serial interval is a fundamentally important quantity in infectious disease epidemiology that has numerous applications to inferring patterns of transmission from case data. Many of these applications are apropos of efforts to eliminate falciparum malaria from locations throughout the world, yet the serial interval for this disease is poorly understood quantitatively. METHODS: To obtain a quantitative estimate of the serial interval for falciparum malaria, the sum of the components of the falciparum malaria transmission cycle was taken based on a combination of mathematical models and empirical data. During this process, a number of factors were identified that account for substantial variability in the serial interval across different contexts. RESULTS: Treatment with anti-malarial drugs roughly halves the serial interval due to an abbreviated period of human infectiousness, seasonality results in different serial intervals at different points in the transmission season, and variability in within-host dynamics results in many individuals whose serial intervals do not follow average behaviour. Furthermore, 24.5 % of secondary cases presenting clinically did so prior to the primary cases being identified through active detection of infection. CONCLUSIONS: These results have important implications for epidemiological applications that rely on quantitative estimates of the serial interval of falciparum malaria and other diseases characterized by prolonged infections and complex ecological drivers. PMID- 27660053 TI - Do Jackhammer contractions lead to achalasia? A longitudinal study. AB - BACKGROUND: Jackhammer esophagus (JE) is a rare esophageal motility disorder defined in the Chicago Classification of Esophageal Motility by presence of excessively high distal contractile integral (DCI) on high-resolution manometry (HRM), with unknown natural manometric course. We examined the development of achalasia over time in patients with JE. METHODS: Through a retrospective longitudinal design, patients with Jackhammer contractions who had more than one HRM between 2005 and 2015 were identified. Any change in manometric finding was assessed for the presence of achalasia. Demographic and manometric risk factors for this progression were then sought in univariate analysis. KEY RESULTS: Of 3363 HRM studies, 229 subjects had multiple manometries, accounting for 528 studies. Twelve subjects met our inclusion criteria for JE on any of the multiple tests, represented by 27 studies for a total of 347 patient-months of manometric follow-up. Subjects with JE whose manometry included impedance demonstrated consistent esophageal bolus clearance. Of 12 subjects with Jackhammer contractions, three subjects progressed to type III achalasia, over a mean of 24 months (range: 19-31 months). At the time of diagnosis with JE, impaired esophago gastric junction relaxation was seen in all three subjects and was the only risk factor that could predict progression to achalasia (P<.01). CONCLUSIONS & INFERENCES: In this unique study of the natural course of JE, we have shown that JE can progress to achalasia. Manometric findings at the time of JE diagnosis might predict this progression. PMID- 27660054 TI - Vaginal prolapse with urinary bladder incarceration and consecutive irreducible rectal prolapse in a dog. AB - BACKGROUND: True vaginal prolapse is a rare condition in dogs and it is occasionally observed in animals with constipation, dystocia, or forced separation during breeding. If a true prolapse occurs, the bladder, the uterine body and/or distal part of the colon, may be present in the prolapse. CASE PRESENTATION: A 2-year-old intact non pregnant Central Asian Shepherd dog in moderate condition, was presented for a true vaginal and rectal prolapse. The prolapses were confirmed by physical examination and ultrasonography. Herniation of the urinary bladder was identified within the vaginal prolapse. The necrotic vaginal wall was resected, the urinary bladder was reduced surgically and fixed to the right abdominal wall to prevent recurrence. Rectal resection and anastomosis was necessary to correct the rectal prolapse. Recurrence of the prolapses was not observed and the dog recovered completely after the surgical treatment. CONCLUSIONS: In our opinion, extreme tenesmus arising from constipation may have predisposed to the vaginal prolapse with bladder incarceration and secondarily to rectal prolapse. In the young female dog, true vaginal prolapse with secondary involvement of the urinary bladder and irreducible rectal prolapse is an exceptionally rare condition. PMID- 27660056 TI - Inflammasome in Dendritic Cells Immunobiology: Implications to Diseases and Therapeutic Strategies. AB - BACKGROUND: An intricate interplay between innate and adaptive immune cells is crucial for an effective immune response during disease, infection and vaccination. This interplay is mainly performed by dendritic cells (DCs), which are professional antigen presenting cells with unparalleled capacity to translate innate to adaptive immunity. They effectively recognize and uptake antigens, migrate to lymphoid tissues, and activate naive T-cells. Indeed, DCs have numerous germline encoded pattern recognition receptors (PRR) that recognize conserved pathogen associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs). While some PRRs like Toll-like receptors (TLRs) recognize PAMPs and DAMPs at the cell surface and in endosomal/lysosomal compartments, others, such as NOD-like receptors (NLRs), act as cytosolic sensors. NLRs activation through recognition of PAMPs and DAMPs leads to the assembly of signaling multimeric protein complexes named inflammasomes. Inflammasomes are important regulators of caspase 1, the enzyme responsible for the proteolytically cleavage of precursors' pro-IL-1beta and pro-IL-18 into their active form. OBJECTIVE: To unveil how inflammasomes are related to maturation, migration, antigen presenting function and DCs ability to fine tune adaptive immune responses. CONCLUSION: Several studies show that in danger/infectious scenarios NLR and TLR synergize to expand DCs maturation, migration, antigen presenting function and adaptive immune system activation. However, in the absence of a danger scenario, and without TLR engagement, inflammasome activation stimulates an immunosuppressive profile on DCs. Overall, it is clear from literature that activation of the inflammasome in DCs should not be viewed in isolation but rather considering its interconnections with the various PPRdriven pathways. Due to the increasing evidences of inflammasome involvement in multiple inflammatory and immune diseases, this information is of utmost importance since precise inflammasome pharmacological targeting could lead to considerable clinical utility through fine-tuned targeted therapies. PMID- 27660055 TI - Diverse responses of wild and cultivated tomato to BABA, oligandrin and Oidium neolycopersici infection. AB - Background and Aims: Current strategies for increased crop protection of susceptible tomato plants against pathogen infections include treatment with synthetic chemicals, application of natural pathogen-derived compounds or transfer of resistance genes from wild tomato species within breeding programmes. In this study, a series of 45 genes potentially involved in defence mechanisms was retrieved from the genome sequence of inbred reference tomato cultivar Solanum lycopersicum 'Heinz 1706'. The aim of the study was to analyse expression of these selected genes in wild and cultivated tomato plants contrasting in resistance to the biotrophic pathogen Oidium neolycopersici , the causative agent of powdery mildew. Plants were treated either solely with potential resistance inducers or by inducers together with the pathogen. Methods: The resistance against O. neolycopersici infection as well as RT-PCR-based analysis of gene expression in response to the oomycete elicitor oligandrin and chemical agent beta-aminobutyric acid (BABA) were investigated in the highly susceptible domesticated inbred genotype Solanum lycopersicum 'Amateur' and resistant wild genotype Solanum habrochaites . Key Results: Differences in basal expression levels of defensins, germins, beta-1,3-glucanases, heveins, chitinases, osmotins and PR1 proteins in non-infected and non-elicited plants were observed between the highly resistant and susceptible genotypes. Moreover, these defence genes showed an extensive up-regulation following O. neolycopersici infection in both genotypes. Application of BABA and elicitin induced expression of multiple defence-related transcripts and, through different mechanisms, enhanced resistance against powdery mildew in the susceptible tomato genotype. Conclusions: The results indicate that non-specific resistance in the resistant genotype S. habrochaites resulted from high basal levels of transcripts with proven roles in defence processes. In the susceptible genotype S. lycopersicum 'Amateur', oligandrin- and BABA-induced resistance involved different signalling pathways, with BABA-treated leaves displaying direct activation of the ethylene dependent signalling pathway, in contrast to previously reported jasmonic acid mediated signalling for elicitins. PMID- 27660057 TI - Associations of cytochrome P450 oxidoreductase genetic polymorphisms with smoking cessation in a Chinese population. AB - Recently, a single nucleotide polymorphism (SNP) A503V (rs1057868) in cytochrome P450 oxidoreductase (POR) gene was reported to influence nicotine metabolism. Considering the importance of nicotine metabolism to smoking cessation, the aim of this study was to investigate the association between POR gene polymorphisms and smoking cessation in a Chinese population. A case-control study was conducted with 363 successful smoking quitters as the cases, and 345 failed smoking quitters as the controls. Eight tagSNPs which cover the entire gene and four functional SNPs were selected and genotyped. Logistic regression was used to explore the relationship between POR SNPs and smoking cessation in codominant, additive, dominant and recessive models. After adjustment for potential confounders, multiple logistic regression analysis indicated that POR rs3823884 and rs3898649 were associated with increased possibility of smoking cessation. Meanwhile, POR rs17685 and rs239953 were shown to have negative effect on successful smoking cessation. No significant differences in the distribution of haplotypes between cases and controls were detected. In conclusion, this study reveals that four SNPs in the POR gene (rs3823884, rs3898649, rs239953 and rs17685) may affect the susceptibility of smoking cessation in a Chinese Han population. PMID- 27660058 TI - Sodium ion transport participates in non-neuronal acetylcholine release in the renal cortex of anesthetized rabbits. AB - This study examined the mechanism of release of endogenous acetylcholine (ACh) in rabbit renal cortex by applying a microdialysis technique. In anesthetized rabbits, a microdialysis probe was implanted into the renal cortex and perfused with Ringer's solution containing high potassium concentration, high sodium concentration, a Na+/K+-ATPase inhibitor (ouabain), or an epithelial Na+ channel blocker (benzamil). Dialysate samples were collected at baseline and during exposure to each agent, and ACh concentrations in the samples were measured by high-performance liquid chromatography. High potassium had no effect on renal ACh release. High sodium increased dialysate ACh concentrations significantly. Ouabain increased dialysate ACh concentration significantly. Benzamil decreased dialysate ACh concentrations significantly both at baseline and under high sodium. The finding that high potassium-induced depolarization does not increase ACh release suggests that endogenous ACh is released in renal cortex mainly by non-neuronal mechanism. Sodium ion transport may be involved in the non-neuronal ACh release. PMID- 27660059 TI - Federally Qualified Health Center Access and Emergency Department Use Among Children. AB - OBJECTIVE: To determine whether increasing access to federally qualified health centers (FQHCs) in California was associated with decreased rates of emergency department (ED) use by children without insurance or insured by Medicaid. METHODS: We combined several data sets to longitudinally analyze 58 California counties between 2005 and 2013. We defined access to FQHCs by county using 2 measures: FQHC sites per 100 square miles between 2005 and 2012 and percentage of Medicaid-insured and uninsured children served by FQHCs from 2008 to 2013. Our outcome was rates of ED use by uninsured or Medicaid-insured children ages 0 to 18 years. To determine the effect of changes in FQHC access on the outcome within a county over time, we used negative binomial models with county fixed effects and controls for preselected time-varying county characteristics and secular trends. RESULTS: Increased geographic density of FQHC sites was associated with <=18% lower rates of ED visits among Medicaid-insured children and <=40% lower ED utilization among uninsured children (P = .05 and P < .01, respectively). However, the percentage of Medicaid-insured and uninsured children seen at FQHCs was not associated with any significant change in ED visit rates among Medicaid insured or uninsured children. CONCLUSIONS: Whereas increased geographic FQHC access was associated with lower rates of ED use by uninsured children, all other measures of FQHC access were not associated with statistically significant changes in pediatric ED use. These results provide community-level evidence that expanding FQHCs may have a limited impact on pediatric ED use, suggesting the need to explore additional factors driving ED utilization. PMID- 27660060 TI - Are FQHCs the Solution to Care Access for Underserved Children? PMID- 27660061 TI - Small Fiber Neuropathy in Children: Two Case Reports Illustrating the Importance of Recognition. AB - Small fiber neuropathy (SFN) is a debilitating condition that often leads to pain and autonomic dysfunction. In the last few decades, SFN has been gaining more attention, particularly in adults. However, literature about SFN in children remains limited. The present article reports the cases of 2 adolescent girls diagnosed with SFN. The first patient (14 years of age) complained about painful itch and tingling in her legs, as well as dysautonomia symptoms for years. She also reported a red/purple-type discoloration of her legs aggravated by warmth and standing, compatible with erythromelalgia. The diagnosis of SFN was confirmed by a reduced intraepidermal nerve fiber density (IENFD) in skin biopsy sample. No underlying conditions were found. Symptomatic neuropathic pain treatment was started with moderate effect. The second patient (16 years of age) developed painful sensations in both feet and hands 6 weeks after an ICU admission for diabetic ketoacidosis, which included dysautonomia symptoms. She also exhibited some signs of erythromelalgia. The patient was diagnosed with predominant SFN (abnormal IENFD and quantitative sensory testing) as well as minor large nerve fiber involvement. Treatment with duloxetine, combined with a rehabilitation program, resulted in a marked improvement in her daily functioning. Although the SFN diagnosis in these 2 cases could be established according to the definition of SFN used in adults, additional diagnostic tools are needed that may be more appropriate for children. Additional information about the course of SFN in children may result in better treatment options. PMID- 27660063 TI - The effect of Me2SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and quality. AB - With the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me2SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 degrees C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration. Here we show that exposure of human bone marrow derived MSCs to Me2SO for >=1 h before freezing, or after thawing, degrades membrane integrity, short-term cell attachment efficiency and alters cell immunophenotype. After 2 h's exposure to Me2SO at 37 degrees C post-thaw, membrane integrity dropped to ~70% and only ~50% of cells retained the ability to adhere to tissue culture plastic. Furthermore, only 70% of the recovered MSCs retained an immunophenotype consistent with the ISCT minimal criteria after exposure. We also saw a similar loss of membrane integrity and attachment efficiency after exposing osteoblast (HOS TE85) cells to Me2SO before, and after, cryopreservation. Overall, these results show that freezing medium exposure is a critical determinant of product quality as process scale increases. Defining and reporting cell sensitivity to freezing medium exposure, both before and after cryopreservation, enables a fair judgement of how scalable a particular cryopreservation process can be, and consequently whether the therapy has commercial feasibility. PMID- 27660062 TI - Reply to Letter: Gastro-Oesophageal Reflux Disease after One-Anastomosis (Mini) Gastric Bypass, Obes Surg 2016;26:1592-3. PMID- 27660064 TI - Clinical significance of coagulase-negative staphylococci other than S. epidermidis blood stream isolates at a tertiary care hospital. AB - PURPOSE: We retrospectively evaluated blood culture (BC) isolates of coagulase negative staphylococci other than Staphylococcus epidermidis (NonSe-CoNS) for clinical relevance at a tertiary care hospital in Germany from January 2011 to September 2015. METHODS: Clinical data were correlated to microbiological results based on medical records. Infection was considered likely if (1) no other infection and (2) two or more isolates of the same species were present and (3) symptoms ameliorated after therapy. Infection was considered possible if a foreign body was present and (1) and (3) were fulfilled. All the other cases were considered contaminations. RESULTS: 313 patients with blood cultures positive for NonSe-CoNS were identified. 61 patients were excluded, either because of missing data or multiple pathogens in the same blood culture. Of the remaining 252 patients, 58 (23 %) were classified as possible (n = 32) or likely (n = 26) infections. S. haemolyticus was the most frequent isolate (infection: n = 28), followed by S. hominis (n = 13), S. capitis (n = 12), and S. lugdunensis (n = 3). One patient died from NonSe-CoNS infection. The source of infection in the majority of patients was foreign bodies (n = 43), and endocarditis was present in six cases. Staphylococci always considered contaminations were: S. auricularis, S. caprae, S. schleiferi, S. pettenkoferi, S. saccharolyticus, and S. simulans. The growth of NonSe-CoNS in the anaerobic BC bottle only and a time to positivity >36 h were associated with contaminations. CONCLUSIONS: One out of four NonSe CoNS isolates was clinically relevant in our cohort, where S. haemolyticus, S. capitis, S. hominis, and S. lugdunensis contributed to 96.6 % of all relevant infections. PMID- 27660065 TI - Responses and recovery pattern of sex steroid hormones in testis of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl. AB - Tilapia were exposed to sublethal methomyl concentrations of 0, 0.2, 2, 20 or 200 MUg/L for 30 days, and then transferred to methomyl-free water for 18 days. The sexual steroid hormones 17beta-estradiol (E2), testosterone (T), and 11 ketotestosterone (11-KT) in tilapia testes were examined at 0, 6, 12, 18, 24 and 30 days after methomyl exposure, and at 18 days after fish were transferred to methomyl-free water. There were no significant changes in the hormone parameters in testes of tilapia exposed to low concentration 0.2 and 2 MUg/L methomyl compared with the controls. However, high concentration 20 and 200 MUg/L methomyl had the potential to disrupt the endocrine system of male tilapia, as shown by an increase in E2 and a decrease in T and 11-KT in the testes. Thus, it would appear that the 2 MUg/L methomyl might be considered the no-observed-adverse-effect level. Recovery data showed that the effects produced by the lower concentration of 20 MUg/L were reversible but the effects were not reversible at the higher concentration of 200 MUg/L. PMID- 27660066 TI - The effect of lead from sediment bioturbation by Lumbriculus variegatus on Daphnia magna in the water column. AB - The present study investigated the bioavailability and potential toxicity to Daphnia magna of lead released to the water column due to bioturbation by Lumbriculus variegatus. Experiments used microcosms with Pb-spiked sediment, with or without worms in the sediment, and with D. magna present in the water column. The daphniids were allowed free movement or were restricted to flow-through containers, in order to assess the influence of their direct contact with the contaminated sediment. A control group consisted of D. magna in clean moderately hard reconstituted water. At the end of the 12-day experiment, D. magna survival, reproduction, biomass, and Pb-bioaccumulation were determined. Water column turbidity and Pb levels were quantified to assess their influence on the Pb toxicity and bioaccumulation. The bioturbation by L. variegatus increased Pb levels and turbidity in the water column. While this resulted in an increased Pb bioaccumulation by the D. magna, the water column Pb levels and the Pb bioaccumulation were insufficient to bring about toxic effects for the survival, reproduction, and biomass of the daphniids. Contact of D. magna with the sediment resulted in an increase in their Pb bioaccumulation, with water turbidity and Pb data, suggesting that these crustaceans also acted as bioturbators. The increase in Pb bioaccumulation in D. magna as a consequence of bioturbation by L. variegatus demonstrates the potential for bioturbation to enhance contaminant toxicity to organisms in the water column, though this potential appeared relatively low in the case of lead. PMID- 27660069 TI - Molecular mechanisms of xeroderma pigmentosum (XP) proteins. AB - Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase n, which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins. PMID- 27660067 TI - Estrogenic compounds in Tunisian urban sewage treatment plant: occurrence, removal and ecotoxicological impact of sewage discharge and sludge disposal. AB - The occurrence, fate and ecotoxicological assessment of selected estrogenic compounds were investigated at Tunisian urban sewage treatment plant. The influents, effluents, as well as primary, secondary and dehydrated sludge, were sampled and analyzed for the target estrogens to evaluate their fate. All target compounds were detected in both sewage and sludge with mean concentrations from 0.062 to 0.993 MUg L-1 and from 11.8 to 792.9 MUg kg-1dry weight, respectively. A wide range of removal efficiencies during the treatment processes were observed, from 6.3 % for estrone to 76.8 % for estriol. Ecotoxicological risk assessment revealed that the highest ecotoxicological risk in sewage effluent and dehydrated sludge was due to 17beta-estradiol with a risk quotient (RQ) of 4.6 and 181.9, respectively, and 17alpha-ethinylestradiol with RQ of 9.8 and 14.85, respectively. Ecotoxicological risk after sewage discharge and sludge disposal was limited to the presence of 17beta-estradiol in dehydrated-sludge amended soil with RQ of 1.38. Further control of estrogenic hormones in sewage effluent and sludge is essential before their discharge and application in order to prevent their introduction into the natural environment. PMID- 27660068 TI - Neck Circumference to Assess Obesity in Preschool Children. AB - OBJECTIVE: Limited information is available about the use of neck circumference (NC) to assess obesity in preschool children. This study aims to provide NC percentiles and determine the cut-off levels of NC as a measure to assess obesity in preschool children. METHODS: The data were obtained from the Anthropometry of Turkish Children aged 0-6 years (ATCA-06) study database. A total of 21 family health centers were chosen and children aged 2-6 years old from all socioeconomic levels were randomly selected from the lists of district midwives; 1766 children (874 male and 892 female; 88.3% of sample size) were included in the study. The smoothed centile curves of NC were constructed by the LMS method. Receiver operating characteristic (ROC) analysis was performed to calculate cut-off points for NC using body mass index >=95th percentile. RESULTS: Mean NC was greater in males than females. Cut-off values for obesity were found to be statistically significant in both genders other than 3 years old boys. The NC percentiles of Turkish preschool children were slightly greater than those of other European preschool children in both genders. This difference disappeared around the adiposity rebound period. The 97th percentile values for Turkish preschool children continue to be greater in both genders. CONCLUSION: NC may be useful to define obesity in preschool children. Since ethnic and various other factors may have a role in incidence of obesity, local reference data are important in assessment of obesity. PMID- 27660070 TI - Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults [Formula: see text]. AB - Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition. PMID- 27660071 TI - Mental health and health-related quality of life of Chinese college students who were the victims of dating violence. AB - PURPOSE: The aim of the study is to evaluate the mental health and health-related quality of life (HRQOL) of Chinese college students who were the victims of dating violence. METHODS: Six hundred and fifty-two subjects were included in the data analysis. Subjects completed a structured questionnaire containing the Woman Abuse Screening tool, the Hospital Anxiety and Depression Scale, the 10-item version of the Perceived Stress Scale (PSS-10) and the World Health Organization Quality of Life-BREF Instrument (WHOQOL-BREF). RESULTS: Analysis by independent t test suggested that victims of dating violence had more severe depressive, anxiety and stress symptoms and poorer HRQOL than non-victims. Multiple linear regression models found that more severe dating violence victimization was associated with more severe depressive, anxiety and stress symptoms. The mediation analysis found that after simultaneously controlling for the degree of depressive, anxiety and stress symptoms, the direct effect between dating violence severity and HRQOL, as measured by overall HRQOL and the global health, physical and environment domains of the WHOQOL-BREF, was statistically insignificant, supporting a full-mediation model. The relationship between dating violence severity and the social domain of HRQOL was partially mediated by the degree of depressive, anxiety and stress symptoms. CONCLUSION: Victims of dating violence had poorer mental health and HRQOL than non-victims. The study findings affirm the importance of assessing depressive, anxiety and stress symptoms in victims and the need to improve their depressive, anxiety and stress symptoms to diminish the negative effects of dating violence, which are apparent in their HRQOL. PMID- 27660072 TI - Neonatal treatment philosophy in Dutch and German NICUs: health-related quality of life in adulthood of VP/VLBW infants. AB - PURPOSE: Although survival after very preterm birth (VP)/very low birth weight (VLBW) has improved, a significant number of VP/VLBW individuals develop physical and cognitive problems during their life course that may affect their health related quality of life (HRQoL). We compared HRQoL in VP/VLBW cohorts from two countries: The Netherlands (n = 314) versus Germany (n = 260) and examined whether different neonatal treatment and rates of disability affect HRQoL in adulthood. METHOD: To analyse whether cohorts differed in adult HRQoL, linear regression analyses were performed for three HRQoL outcomes assessed with the Health Utilities Index 3 (HUI3), the London Handicap Scale (LHS), and the WHO Quality of Life instrument (WHOQOL-BREF). Stepwise hierarchical linear regression was used to test whether neonatal physical health and treatment, social environment, and intelligence (IQ) were related to VP/VLBW adults' HRQoL and cohort differences. RESULTS: Dutch VP/VLBW adults reported a significantly higher HRQoL on all three general HRQoL measures than German VP/VLBW adults (HUI3: .86 vs .83, p = .036; LHS: .93 vs. .90, p = .018; WHOQOL-BREF: 82.8 vs. 78.3, p < .001). Main predictor of cohort differences in all three HRQoL measures was adult IQ (p < .001). CONCLUSIONS: Lower HRQoL in German versus Dutch adults was related to more cognitive impairment in German adults. Due to different policies, German VP/VLBW infants received more intensive treatment that may have affected their cognitive development. Our findings stress the importance of examining effects of different neonatal treatment policies for VP/VLBW adults' life. PMID- 27660073 TI - Affective Biases in Humans and Animals. AB - Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies. PMID- 27660074 TI - Effects of Supplemental Chromium Propionate on Serum Lipids, Carcass Traits, and Meat Quality of Heat-Stressed Broilers. AB - This study was conducted to investigate the effects of chromium from chromium propionate (CrPro) on serum lipids, carcass traits, and breast meat quality in heat-stressed birds. A total of 210 1-day-old male broilers were randomly allotted by initial body weight (BW) into 5 treatments with 7 replicates with 6 birds per replicate pen for 42 days. The treatments included a basal corn-soybean meal diet and basal diet supplemented with 0.2, 0.4, 0.8, or 1.6 mg Cr/kg diet. Birds had ad libitum access to feed and distilled-deionized water at normal conditions for 1-3 weeks with little or no stress, and then birds were housed under heat stress conditions with 35 +/- 2 degrees C ambient temperature for 4-6 weeks. Results showed that serum triglyceride (TG) (P = 0.0006) and low-density lipoprotein cholesterol (LDLC) (P = 0.0038) concentrations were decreased linearly as Cr dose increased. Compared with other groups, birds receiving 0.8 or 1.6 mg Cr/kg had lower TG (P = 0.0015). Compared to control birds, birds fed diets with 0.2, 0.4, 0.8, or 1.6 mg Cr/kg supplementation had lower LDLC (P = 0.0006). However, the total cholesterol (TC) and high density lipoprotein cholesterol (HDLC) concentrations in serum were not affected by treatment (P > 0.05). No difference was observed in BW, the relative weights of breast muscle, thigh muscle and abdominal fat (P > 0.05), and breast meat quality (Ph15min, Ph24h, L*, a*, b*, cooking loss, shear force) among the treatments (P > 0.05). Results from this study indicated that CrPro supplementation could be beneficial to serum lipids metabolism of heat-stressed broiler chickens by decreasing TG and LDLC contents, but had no impacts on meat quality and carcass traits of the heat stressed broilers. PMID- 27660075 TI - HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells. AB - Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4alpha (HNF-4alpha) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4alpha on hepcidin expression was observed by transfecting specific HNF-4alpha small interfering RNA (siRNA) or plasmids into HepG2 cells. Both direct and indirect mechanisms involved in the regulation of HNF-4alpha on hepcidin were detected by real-time PCR, Western blotting, chromatin immunoprecipitation (chIP), and reporter genes. It was found that HNF 4alpha suppressed hepcidin messenger RNA (mRNA) and protein expressions in HepG2 cells, and this suppressive effect was independent of the potential HNF-4alpha response elements. Phosphorylation of SMAD1 but not STAT3 was inactivated by HNF 4alpha, and the SMAD4 response element was found essential to HNF-4alpha-induced hepcidin reduction. Neither inhibitory SMADs, SMAD6, and SMAD7 nor BMPR ligands, BMP2, BMP4, BMP6, and BMP7 were regulated by HNF-4alpha in HepG2 cells. BMPR1A, but not BMPR1B, BMPR2, ActR2A, ActR2B, or HJV, was decreased by HNF-4alpha, and HNF4alpha-knockdown-induced stimulation of hepcidin could be entirely blocked when BMPR1A was interfered with at the same time. In conclusion, the present study suggests that HNF-4alpha has a suppressive effect on hepcidin expression by inactivating the BMP pathway, specifically via BMPR1A, in HepG2 cells. PMID- 27660077 TI - Mechanisms underlying long-term fear memory formation from a metaplastic neuronal state. AB - We previously showed that a single weak fear conditioning trial, that does not produce a long-term fear memory (LTM), appeared to prime memory formation such that when a second trial followed within a circumscribed time window a robust and long-lasting fear memory was formed. We also showed that this priming effect could be blocked if we interfered with protein kinase A (PKA) signaling in the amygdala during the first conditioning trial. The goals of the current study were to determine if LTM formation after the second trial depends on PKA signaling in the amygdala and to characterize the underlying memory processes engaged during the second trial that allows for LTM formation. Our interpretation of the original findings is that the second conditioning trial triggers LTM from a metaplastic state that is engaged by the first conditioning trial. However, it is also possible that the second conditioning trial acts as a reminder of the first and engages a reconsolidation-like process. Several experiments were conducted to distinguish between these two possibilities. We show that interfering with PKA signaling during the second conditioning trial disrupts memory formation. However, if a third trial follows the second or if the second trial was presented without shock, the PKA inhibitor was no longer effective. Our findings demonstrate that the induction of fear memory from a metaplastic state involves new learning that is distinct from retrieval-dependent updating of memories. PMID- 27660078 TI - Naloxone blocks the aversive effects of electrical stimulation of the parabrachial complex in a place discrimination task. AB - The parabrachial complex is known to participate in various rewarding and aversive processes, including those related to the learning of taste or place discrimination and the motivational effects of drugs of abuse, such as morphine. This study shows that electrical stimulation of the external lateral parabrachial (LPBe) subnucleus induces consistent place avoidance or place preference in three compartment rectangular mazes. Administration of naloxone, an opiate antagonist, blocks both motivational effects induced by the intracranial electrical stimulation. Subsequent re-administration of the electrical stimulation was found to recover its aversive but not its rewarding effects after vehicle administration. These results are discussed in relation to different natural and artificial agents involved in the induction of avoidance and preference motivational processes, especially with regard to the opioid system. PMID- 27660076 TI - Impaired function of alpha2-containing nicotinic acetylcholine receptors on oriens-lacunosum moleculare cells causes hippocampus-dependent memory impairments. AB - Children of mothers who smoked during pregnancy are at significantly greater risk for cognitive impairments including memory deficits, but the mechanisms underlying this effect remain to be understood. In rodent models of smoking during pregnancy, early postnatal nicotine exposure results in impaired long-term hippocampus-dependent memory, functional loss of alpha2-containing nicotinic acetylcholine receptors (alpha2* nAChRs) in oriens-lacunosum moleculare (OLM) cells, increased CA1 network excitation, and unexpected facilitation of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses. Here we demonstrate that alpha2 knockout mice show the same pattern of memory impairment as previously observed in wild-type mice exposed to early postnatal nicotine. However, alpha2 knockout mice and alpha2 knockout mice exposed to early postnatal nicotine did not share all of the anomalies in hippocampal function observed in wild-type mice treated with nicotine during development. Unlike nicotine-treated wild-type mice, alpha2 knockout mice and nicotine-exposed alpha2 knockout mice did not demonstrate increased CA1 network excitation following Schaffer collateral stimulation and facilitated LTP, indicating that the effects are likely adaptive changes caused by activation of alpha2* nAChRs during nicotine exposure and are unlikely related to the associated memory impairment. Thus, the functional loss of alpha2* nAChRs in OLM cells likely plays a critical role in mediating this developmental-nicotine-induced hippocampal memory deficit. PMID- 27660079 TI - Comparison of fluorescence probes for intracellular sodium imaging in prostate cancer cell lines. AB - Sodium (Na+) ions are known to regulate many signaling pathways involved in both physiological and pathological conditions. In particular, alterations in intracellular concentrations of Na+ and corresponding changes in membrane potential are known to be major actors of cancer progression to metastatic phenotype. Though the functionality of Na+ channels and the corresponding Na+ currents can be investigated using the patch-clamp technique, the latter is rather invasive and a technically difficult method to study intracellular Na+ transients compared to Na+ fluorescence imaging. Despite the fact that Na+ signaling is considered an important controller of cancer progression, only few data using Na+ imaging approaches are available so far, suggesting the persisting challenge within the scientific community. In this study, we describe in detail the approach for application of Na+ imaging technique to measure intracellular Na+ variations in human prostate cancer cells. Accordingly, we used three Na+ specific fluorescent dyes-Na+-binding benzofuran isophthalate (SBFI), CoroNaTM Green (Corona) and Asante NaTRIUM Green-2 (ANG-2). These dyes have been assessed for optimal loading conditions, dissociation constant and working range after different calibration methods, and intracellular Na+ sensitivity, in order to determine which probe can be considered as the most reliable to visualize Na+ fluctuations in vitro. PMID- 27660080 TI - Impact of Routine Surveillance Imaging on Outcomes of Patients With Diffuse Large B-Cell Lymphoma After Autologous Hematopoietic Cell Transplantation. AB - BACKGROUND: For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), autologous hematopoietic cell transplantation (auto-HCT) is commonly used. After auto-HCT, DLBCL patients are often monitored with surveillance imaging. However, there is little evidence to support this practice. PATIENTS AND METHODS: We performed a multicenter retrospective study of DLBCL patients who underwent auto-HCT (n = 160), who experienced complete remission after transplantation, and who then underwent surveillance imaging. Of these, only 45 patients experienced relapse after day +100 after auto-HCT, with relapse detected by routine imaging in 32 (71%) and relapse detected clinically in 13 (29%). RESULTS: Baseline patient characteristics were similar between the 2 groups. Comparing the radiographic and clinically detected relapse groups, the median time from diagnosis to auto-HCT (389 days vs. 621 days, P = .06) and the median follow-up after auto-HCT (2464 days vs. 1593 days P = .60) were similar. The median time to relapse after auto-HCT was 191 days in radiographically detected relapses compared to 492 days in clinically detected relapses (P = .35), and median postrelapse survival was 359 days in such patients compared to 123 days in patients with clinically detected relapse (P = .36). However, the median posttransplantation overall survival was not significantly different for patients with relapse detected by routine imaging versus relapse detected clinically (643 vs. 586 days, P = .68). CONCLUSION: A majority (71%) of DLBCL relapses after auto HCT are detected by routine surveillance imaging. Overall, there appears to be limited utility for routine imaging after auto-HCT except in select cases where earlier detection and salvage therapy with allogeneic HCT is a potential option. PMID- 27660081 TI - Validity and Reliability of the Indonesian Version of the Brief Fatigue Inventory in Cancer Patients. AB - CONTEXT: Cancer-related fatigue is one of the most commonly reported symptoms in cancer patients. Short but good assessment is essential to detect and manage this symptom. Brief Fatigue Inventory (BFI) is a valid and reliable short instrument to assess cancer-related fatigue. OBJECTIVE: To examine the validity and reliability of the Indonesian BFI. METHODS: Forward and backward translation approach, followed by cognitive debriefing process, was done to develop Indonesian BFI. One hundred twenty-one consecutive adult outpatients with cancer who are willing to participate in this study filled in Indonesian BFI along with the Medical Outcome Study Quality of Life Short Form 36 (MOS SF-36). Demographic and health data were collected. RESULTS: The Indonesian BFI had an overall Cronbach's alpha for the nine items of 0.956. The results of the factor analysis suggested a one-factor solution, supporting the hypothesis of unidimensionality of the Indonesian BFI. The Indonesian BFI score was compared with MOS SF-36 subscale to evaluate convergent validity. An expected inverse correlation between Indonesian BFI and all domains of MOS SF-36 was observed (r = -0.388 to -0.676; P < 0.0000). Discriminant validity analysis showed that the Indonesian BFI mean score significantly increased with increasing Eastern Cooperative Oncology Group Performance Status values (P = 0.000). CONCLUSION: Indonesian BFI is a reliable and valid instrument for Indonesian cancer patients. PMID- 27660082 TI - Nationwide Japanese Survey About Deathbed Visions: "My Deceased Mother Took Me to Heaven". AB - OBJECTIVES: Primary aim was to clarify the prevalence and factors associated with the occurrence of deathbed visions, explore associations among deathbed visions, a good death, and family depression. Additional aim was to explore the emotional reaction, perception, and preferred clinical practice regarding deathbed visions from the view of bereaved family members. METHODS: A nationwide questionnaire survey was conducted involving 3964 family members of cancer patients who died at hospitals, palliative care units, and home. RESULTS: A total of 2827 responses (71%) were obtained, and finally 2221 responses were analyzed. Deathbed visions were reported in 21% (95% CIs, 19-23; n = 463). Deathbed visions were significantly more likely to be observed in older patients, female patients, female family members, family members other than spouses, more religious families, and families who believed that the soul survives the body after death. Good death scores for the patients were not significantly different between the families who reported that the patients had experienced deathbed visions and those who did not, whereas depression was more frequently observed in the former than latter, with marginal significance (20 vs. 16%, respectively, adjusted P = 0.068). Although 35% of the respondents agreed that deathbed visions were hallucinations, 38% agreed that such visions were a natural and transpersonal phenomenon in the dying process; 81% regarded it as necessary or very necessary for clinicians to share the phenomenon neutrally, not automatically labeling them as medically abnormal. CONCLUSIONS: Deathbed vision is not an uncommon phenomenon. Clinicians should not automatically regard such visions as an abnormal phenomenon to be medically treated and rather provide an individualized approach. PMID- 27660083 TI - After the Spiritual Assessment. PMID- 27660084 TI - Psychometric Characteristics of the Hebrew Version of the Professional Quality-of Life Scale. AB - CONTEXT: Exposure to human suffering may have ramifications for the professional quality of life (ProQol) of palliative care teams. The ProQol scale was designed to assess both negative and positive work-related outcomes and has been used recently for the evaluation of work-related outcomes among palliative care workers. However, the assessment of ProQol among Israeli hospice workers is scant. OBJECTIVES: The aim of this study was to assess the psychometric properties and the factor structure of the Hebrew version of the 30-item ProQol questionnaire. METHODS: The study population included 1100 health care providers including physicians, nurses, and social workers in primary health care and palliative care settings. RESULT: A total of 380 workers participated in the study, representing a response rate of 34.5%. The confirmatory factor analysis did not show an adequate "goodness to fit." Using a factor coefficient of 0.35 or greater for inclusion, the exploratory factor analysis revealed a 23-item solution, loaded onto three factors: compassion satisfaction, secondary traumatic stress, and burnout (BU). The internal consistency subscales were 0.87, 0.82, and 0.69, respectively. The subscales showed good convergent and exploratory validity because of significant correlations with measures that examine BU, work engagement, and peritraumatic dissociative experiences. CONCLUSIONS: Although the findings are consistent with those from studies in other languages, they are different from the original 30-item three-factor structure reported by Stamm. The Hebrew version of the compassion satisfaction subscale was found to be reliable and valid for studies among health care professionals, but further research is needed to improve the BU and secondary traumatic stress subscales. PMID- 27660085 TI - Aging and anti-aging. PMID- 27660087 TI - Childhood hyperactivity and mood problems at mid-life: evidence from a prospective birth cohort. AB - PURPOSE: Childhood hyperactivity leads to mental health problems, but it is not known whether there are long-term risks for adult mood problems in unselected population cohorts that extend to mid-life. Aims were to examine links between childhood hyperactivity and mood problems up to age 50 years and to consider confounding factors and gender differences in associations. METHODS: The National Child Development Study (NCDS) is a UK cohort of children born in 1958. Children with (N = 453) and without (N = 9192) pervasive and persistent hyperactivity were followed to age 50. Adult mood was assessed using the Malaise Inventory at ages 23, 33, 42, and 50 years and the CIS-R interview at 45 years. RESULTS: Childhood hyperactivity predicted low mood at all adult assessments (ES = 0.27-0.45), including after covariate adjustment (childhood adversity, emotional and behavioural problems, and attainment). CONCLUSION: Hyperactivity has enduring risk effects on low mood throughout the life course that extend to middle age. PMID- 27660088 TI - Antibacterial in vitro effects of preparations from Anthroposophical Medicine. AB - BACKGROUND: Medications from Anthroposophical Medicine (AM) are clinically used for the treatment of infections within a whole medical system but have not yet been evaluated regarding antibacterial effects. The aims of this study was to investigate antibacterial activity of AM medications in cell culture. METHODS: Screening of AM drug registers for preparations used to treat any kind of infection and being available in dilutions <= D2 and without alcoholic content. Selected medications were screened for antimicrobial activity against Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa using the agar diffusion method. For antimicrobial active preparations growth kinetics (drop plate method) and minimal inhibitory concentrations (MIC, macrodilution method) were determined. RESULTS: Thirty-three preparations matched the selection criteria and were chosen for own experiments. One of them (Berberis Decoctum D2) exhibited bactericidal activities against Bacillus subtilis and Staphylococcus aureus, including methicillin resistant strains. The MIC could be determined as 5 mg/ml. The effects could be related to the content of berberine in the extract. No activity towards gram-negative bacteria was found. The other tested extracts had no antibacterial effects. CONCLUSION: Berberis Decoctum D2 which is used in AM to treat infections exhibits bactericidal effects on Staphylococcus aureus, including methicillin resistant strains. PMID- 27660089 TI - Prevention of Infection Due to Clostridium difficile. AB - Clostridium difficile is one of the foremost nosocomial pathogens. Preventing infection is particularly challenging. Effective prevention efforts typically require a multifaceted bundled approach. A variety of infection control procedures may be advantageous, including strict hand decontamination with soap and water, contact precautions, and using chlorine-containing decontamination agents. Additionally, risk factor reduction can help reduce the burden of disease. The risk factor modification is principally accomplished though antibiotic stewardship programs. Unfortunately, most of the current evidence for prevention is in acute care settings. This review focuses on preventative approaches to reduce the incidence of Clostridium difficile infection in healthcare settings. PMID- 27660090 TI - Multidrug-Resistant Gram-Negative Bacilli: Infection Control Implications. AB - Antimicrobial resistance is a common iatrogenic complication of both modern life and medical care. Certain multidrug resistant and extensively drug resistant Gram negative organisms pose the biggest challenges to health care today, predominantly owing to a lack of therapeutic options. Containing the spread of these organisms is challenging, and in reality, the application of multiple control measures during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article reviews the usefulness of various infection control measures in containing the spread of multidrug-resistant Gram negative bacilli. PMID- 27660091 TI - Vancomycin-Resistant Enterococci: Epidemiology, Infection Prevention, and Control. AB - Vancomycin-resistant enterococci (VRE) infections have acquired prominence as a leading cause of health care-associated infections. Understanding VRE epidemiology, transmission modes in health care settings, risk factors for colonization, and infection is essential to prevention and control of VRE infections. Infection control strategies are pivotal in management of VRE infections and should be based on patient characteristics, hospital needs, and available resources. Hand hygiene is basic to decrease acquisition of VRE. The effectiveness of surveillance and contact precautions is variable and controversial in endemic settings, but important during VRE outbreak investigations and control. Environmental cleaning, chlorhexidine bathing, and antimicrobial stewardship are vital in VRE prevention and control. PMID- 27660092 TI - Preventing Transmission of Mycobacterium tuberculosis in Health Care Settings. AB - Patients with tuberculosis (TB) pose a risk to other patients and health care workers, and outbreaks in health care settings occur when appropriate infection control measures are not used. In this article, we discuss strategies to prevent transmission of Mycobacterium tuberculosis within health care settings. All health care facilities should have an operational TB infection control plan that emphasizes the use of a hierarchy of controls (administrative, environmental, and personal respiratory protection). We also discuss resources available to clinicians who work in the prevention and investigation of nosocomial transmission of M tuberculosis. PMID- 27660093 TI - Association study of rs924080 and rs11209032 polymorphisms of IL23R-IL12RB2 in a Northern Chinese Han population with Behcet's disease. AB - OBJECTIVES: Two genome-wide association studies (GWAS) have identified the IL-23 receptor- IL-12 receptor beta2 (IL23R-IL12RB2) as the susceptibility genetic region in Turkish and Japanese population with Behcet's disease (BD). We investigated the association of this region with BD in a Northern Chinese Han population. METHODS: A total of 407 patients with BD and 421 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) rs924080 and rs11209032 using the Sequenom MassArray system. RESULTS: Statistically significant associations with BD were detected at two SNPs namely, rs924080 and rs11209032, both, by allele analysis (OR=1.58, 95% CI=1.25-2.00, Pc=2.52*10-4, and OR=1.45, 95% CI=1.19-1.76, Pc=3.46*10-4, respectively), and genotype analysis (Pc=1.22*10 3andPc=1.77*10-3, respectively). Significant differences were observed in the genotype frequency distribution for these SNPs under the additive, dominant and recessive models (all Pc<0.05). The haplotypes (AT and GC) formed by the two SNPs were associated with BD (all permutation P<0.05). A meta-analysis also appeared to support the association of the two SNPs with BD. CONCLUSION: SNPs (rs924080 and rs11209032) of the IL23R-IL12RB2 region were found to be associated with BD in a Northern Chinese Han population. PMID- 27660095 TI - Population structure and marker-trait association of salt tolerance in barley (Hordeum vulgare L.). AB - Association mapping is becoming an important tool for identifying alleles and loci responsible for dissecting highly complex traits in barley. This study describes the population structure and marker-trait association using general linear model (GLM) analysis on a site of 60 barley genotypes, evaluated in six salinity environments. Ninety-eight SSR and SNP alleles were employed for the construction of a framework genetic map. The genetic structure analysis of the collection turned out to consist of two major sub-populations, mainly comprising hulled and naked types. LD significantly varied among the barley chromosomes, suggesting that this factor may affect the resolution of association mapping for QTL located on different chromosomes. Numerous significant marker traits were associated in different regions of the barley genome controlling salt tolerance and related traits; among them, 46 QTLs were detected on 14 associated traits over the two years, with a major QTL controlling salt tolerance on 1H, 2H, 4H and 7H, which are important factors in improving barley's salt tolerance. PMID- 27660094 TI - Effect of interleukin-10 gene promoter polymorphisms -1082 G/A and -592 C/A on response to therapy in children and adolescents with chronic hepatitis C virus infection. AB - BACKGROUND AND AIM: Studying predictors of response to therapy for hepatitis C virus (HCV) infection in children may help avoid the inappropriate use of currently available costly therapy associated with numerous adverse effects. We tested the hypothesis that inheritance of single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) promoter gene might influence response to HCV treatment. PATIENTS AND METHODS: The impact of SNPs, -1082 G/A and -592 C/A, in the promoter region of IL-10 gene, on response to HCV therapy was assessed in a cohort of 40 children treated with a combination of pegylated interferon (Peg IFN) alpha2b and ribavirin. RESULTS: Sustained virological response was achieved in 48.7%. High viral load was associated with non-response to therapy. There was no association between histopathological degree of inflammation or fibrosis and response to therapy. There was no direct statistically significant association between polymorphisms in the IL-10 gene (-1082G/A and -592 C/A) as regards inflammation or response to therapy in children. As for the SNP -592 C/A; there was a statistically significant association with the score of fibrosis (P<0.004), concluding that the A allele was protective from moderate and severe fibrosis. Meanwhile the SNP -1082G/A did not show any association with the fibrosis score. CONCLUSION: We could not associate response to therapy for HCV with IL-10 polymorphisms -1082 G/A and -592 C/A. For the SNP -592 C/A, the A allele protected from moderate and severe fibrosis. PMID- 27660096 TI - Arterial Pulmonary Hypertension Secondary to Partial Anomalous Pulmonary Venous Return in an Elderly Patient. PMID- 27660097 TI - Enhanced cyanophycin production by Escherichia coli overexpressing the heterologous cphA gene from a deep sea metagenomic library. AB - Cyanophycin is a non-ribosomally synthesized polymer and its microbial production has attracted increased attention due to its pharmaceutical and chemical values. For the characterization and production of cyanophycin, the cphA49 gene was cloned and expressed in Escherichia coli. Soluble cyanophycin was isolated from the cultures and characterized. The results showed that it was composed of 50% of aspartic acid, 45% of arginine, and 3.5% of lysine, and exhibited a homogenous molecular mass of 35 kDa. To improve soluble cyanophycin production, the induction conditions for cphA49 gene expression were optimized. Meanwhile, the effects of medium content and induction duration on soluble cyanophycin production were also investigated, and the soluble cyanophycin yield reached a maximum at 72 h. Finally, to further increase the soluble cyanophycin production, the cultivation was carried out by supplement of arginine, aspartic acid, lysine and glucose into the minimal resource medium after cphA49 gene expression level was improved under optimized conditions, and the maximum concentration of soluble cyanophycin reached 1.72 g/L. PMID- 27660098 TI - Identification of a putative FR901469 biosynthesis gene cluster in fungal sp. No. 11243 and enhancement of the productivity by overexpressing the transcription factor gene frbF. AB - FR901469 is an antifungal antibiotic produced by fungal sp. No. 11243. Here, we searched for FR901469 biosynthesis genes in the genome of No. 11243. Based on the molecular structure of FR901469 and endogenous functional motifs predicted in each genomic NRPS gene, a putative FR901469 biosynthesis gene cluster harboring the most plausible NRPS gene was identified. A transcription factor gene, designated frbF, was found in the cluster. To improve FR901469 productivity, we constructed a strain in which frbF was overexpressed and named it TFH2-2. FR901469 productivity of TFH2-2 was 3.4 times higher than that of the wild-type strain. Transcriptome analysis revealed that most of the genes in the putative FR901469 biosynthesis gene cluster were upregulated in TFH2-2. It also showed that the expression of genes related to ergosterol biosynthesis, beta-1,3-glucan catabolism, and chitin synthesis was inclined to exhibit significant differences in TFH2-2. PMID- 27660099 TI - Molecular insight into the dynamic central metabolic pathways of Achromobacter xylosoxidans CF-S36 during heterotrophic nitrogen removal processes. AB - Organic carbon sources play a significant role in heterotrophic nitrogen consumption. This quintessential exploration is focused on carbon and nitrogen biogeochemical cycles in heterotrophic bacteria, capable of simultaneous nitrification and denitrification (SND). A heterotrophic bacterial strain Achromobacter xylosoxidans CF-S36 isolated from domestic wastewater efficiently eliminated ammonia, nitrate and nitrite by utilizing different carbon sources. The type of carbon utilized by strain CF-S36 determined the rate of heterotrophic nitrogen removal. Quantitative real-time PCR (qRT-PCR) analysis of genes of central carbon and nitrogen metabolism, signal transduction, electron transport chain (ETC) pathways and assays of enzymes of denitrification processes revealed the existence of well-coordinated link between carbon utilization and nitrogen elimination in bacterial cell. The most preferred carbon source for nitrification was succinate followed by glucose and acetate. Inhibitory effect of nitrite on glycolytic pathway and nitrogen assimilation genes attributes glucose as unfavorable carbon source for denitrification process in strain CF-S36. Acetate served as efficient carbon source for utilizing nitrite through denitrification process. The study demonstrated here might be useful to biogeochemical engineer to understand the involvement of heterotrophic bacteria in global biogeochemical cycle and to gain further insight into the diversified application of these microorganisms. PMID- 27660100 TI - The relation between angioarchitectural factors of developmental venous anomaly and concomitant sporadic cavernous malformation. AB - BACKGROUND: Past studies found that cerebral developmental venous anomaly (DVA) is often concurrent with cavernous malformation (CM). But the reason of the concurrency remains unknown. The purpose of this study was to confirm whether angioarchitectural factors relate to the concurrence and which angioarchitectural factors can induce the concurrency. METHODS: DVA cases were selected from the records of the same 3.0 T MR. The DVA cases was divided into two group which are DVA group and DVA concurrent with CM group. 8 angioarchitectural factors of the DVAs were selected and measured. Statistical analysis was performed by the Pearson chi-square statistic,analysis of variance (ANOVA) and multi-factor logistic regression analysis. RESULTS: Five hundred three DVA lesions were found and 76 CM lesions coexisting with DVA. In the single factor analysis, all the 8 angioarchitectural factors of DVA were related to the concurrency. In the multivariate analysis, 6 angioarchitectural factors. Result of multi-factor logistic regression analysis is Logit(P) = -4.858-0.932(Location) + 1.616(Direction) + 1.757(Torsion) + 0.237(Number) + 2.119(Stenosis rate of medullary vein)-0.015(Angle), goodness of fit is 90.1 %. CONCLUSIONS: The angioarchitectural factors of DVA are related to the concurrency of DVA and CM. 6 angioarchitectural factors may induce the concurrency. PMID- 27660102 TI - World will lack 18 million health workers by 2030 without adequate investment, warns UN. PMID- 27660101 TI - Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo. AB - Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells. RD-N was administrated for 25days. The specimens of xenografts in Balb/c athymic (nu+/nu+) male mice were removed for immunohistochemistry, subcellular fractionation, enzyme activities and Western blotting analysis. mRFP-GFP-LC3 reporter was used to examine autophagy in H460 cells. Sphingomyelin assay was evaluated by thin layer chromatography and assay kit. Lysosomal membrane permeabilization (LMP) caused by acid sphingomyelinase (ASM) inhibition and subsequent changes of sphingomyelin (SM) metabolism selectively destabilized the cancer cell lysosomes in RD-N-treated H460 cells in vitro and tumor xenograft model in vivo. The destabilized lysosomes induced the release of cathepsins from the lysosomes into the cytosol and further triggered cell death. These results explain the underlying mechanism of RD-N induced LMP. It can be concluded that a more lysosomotropic derivative was synthesized by introduction of an amine group, which could have more potential applications in cancer therapy. PMID- 27660104 TI - Impact of the age at menarche on body composition in adulthood: results from two birth cohort studies. AB - BACKGROUND: Evidence suggests that early menarche is positively associated with adiposity in adulthood. However, it is important to assess whether this association is due to early menarche or to the association of adiposity in late childhood with age at menarche. We evaluated the association between age at menarche and body composition in adolescence and adulthood, among subjects who have been prospectively followed in two Brazilian birth cohort studies. METHODS: In 1982 and 1993, the hospitals births in Pelotas were identified, and these subjects have been followed for several times. Information on age at menarche was obtained from the women (1982 cohort) and their mothers (1993 cohort). At 30 and 18 years, the following body composition measures were evaluated: body mass index, waist circumference, fat-free mass index and fat mass index measured by dual-energy x-ray absorptiometry, and thickness of the abdominal visceral fat layer measured by ultrasound. The analyses were adjusted for: birth weight, maternal pregestational weight, gestational age, family income, household score index, maternal schooling, weight-for-height z-score at 4 years (1982), and body mass index at 11 years (1993). RESULTS: At 30 and 18 years, 2045 and 2092 women were evaluated, respectively. The prevalence of early menarche (<=11 years of age) was 24.7 % in the 1982 and 27.6 % in the 1993 cohort. In the 1982 cohort, early menarche was positively associated with all body composition variables compared to those with late menarche (>=14 years of age) even after adjusting for confounders (fat mass index: 2.33 kg/m2, 95 % Confidence interval: 1.64; 3.02). However, in the 1993 cohort, after adjusting for body mass index at 11 years, the regression coefficient for the association with fat mass index decreased from 2.2 kg/m2 (95 % Confidence interval: 1.7; 2.6) to 0.26 (95 % Confidence interval: 0.08; 0.60). CONCLUSIONS: The association between age at menarche and body composition in adulthood is strongly explained by pre-pubertal adiposity. PMID- 27660103 TI - Activated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX2 expression via TNF-alpha. AB - Orthodenticle homeobox 2 (OTX2) controls essential, homeostatic retinal pigment epithelial (RPE) genes in the adult. Using cocultures of human CD14+ blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human-induced pluripotent stem cell-derived RPE cells, we show that activated Mos markedly inhibit RPEOTX2 expression and resist elimination in contact with the immunosuppressive RPE. Mechanistically, we demonstrate that TNF-alpha, secreted from activated Mos, mediates the downregulation of OTX2 and essential RPE genes of the visual cycle among others. Our data show how subretinal, chronic inflammation and in particular TNF-alpha can affect RPE function, which might contribute to the visual dysfunctions in diseases such as age-related macular degeneration (AMD) where subretinal macrophages are observed. Our findings provide important mechanistic insights into the regulation of OTX2 under inflammatory conditions. Therapeutic restoration of OTX2 expression might help revive RPE and visual function in retinal diseases such as AMD. PMID- 27660105 TI - A chemogenomic approach to understand the antifungal action of Lichen-derived vulpinic acid. AB - AIM: To determine uncovered antifungal activity of lichen-derived compound, vulpinic acid, by using chemical-genetic analyses. METHODS AND RESULTS: Haploinsufficiency and homozygous-profiling assays were performed, revealing that strains lacking GLC7, MET4, RFC2, YAE1 and PRP18 were sensitive to three concentrations (12.5, 25 and 50% of inhibitory concentration) of vulpinic acid and independently validated. To verify inhibition of those genes, cell cycle analysis using flow cytometry was performed and relative expressions were measured. Under vulpinic acid-treated condition, cell cycle was arrested in S and G2/M phases and sensitive strains' relative expressions were significantly lower than the wild type yeast. CONCLUSIONS: Vulpinic acid mainly affects cell cycle, glycogen metabolism, transcription and translation to fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Although lichen-derived compounds are commercially valuable, few studies have determined their modes of action. This study used a chemogenomic approach to gain insight into the mechanisms of one of well-known lichen-derived compound, vulpinic acid. PMID- 27660106 TI - Gout mimicking rheumatoid arthritis. PMID- 27660107 TI - Child Characteristics, Parent Education and Depressive Symptoms, and Marital Conflict Predicting Trajectories of Parenting Behavior from Childhood Through Early Adolescence in Taiwan. AB - The study examined how child and parent characteristics, and contextual sources of stress, such as marital conflict predict initial status and trajectories of parent involvement, support, and harsh control, over a 4-year period in families in Taiwan (n = 4,754). Based on Belsky's (1984) ecological model of parenting, three domains predicting parenting were tested, child characteristics (age cohort and gender), father and mother characteristics (education and depressive symptoms), and contextual sources of stress (marital conflict). The study followed two cohorts of children; the younger cohort was followed from first to fourth grade and the older cohort from fourth to seventh grade. Initially, fourth graders reported more parental involvement, support, and harsh control than first graders. However, involvement, support, and harsh control decreased across the 4 years for the older cohort as they transitioned to early adolescence. In the first year, girls reported more parental involvement and support and less harsh control than boys. Across the 4 years, involvement and support increased, and harsh control decreased for boys; whereas involvement stayed the same, support slightly decreased, and harsh control slightly increased for girls. Children whose parents were more educated reported more parent involvement, support, and harsh control in the first year. Children whose fathers were chronically depressed and whose parents were experiencing marital conflict reported decreasing parent involvement and support over the years. PMID- 27660108 TI - Myocardial late gadolinium enhancement is associated with clinical presentation in Duchenne muscular dystrophy carriers. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that occurs in males leading to immobility and death in early adulthood. Female carriers of DMD are generally asymptomatic, yet frequently develop dilated cardiomyopathy. This study aims to detect early cardiac manifestation in DMD using cardiovascular magnetic resonance (CMR) and to evaluate its association with clinical symptoms. METHODS: Clinical assessment of DMD carriers included six minutes walk tests (6MWT), blood analysis, electrocardiography, echocardiography, and CMR using FLASH sequences to detect late gadolinium enhancement (LGE). T1 mapping using the Modified Look-Locker Inversion recovery (MOLLI) sequence was performed quantify extracellular volume (ECV). RESULTS: Of 20 carriers (age 39.47 +/- 12.96 years) 17 (89.5 %) were clinically asymptomatic. ECV was mildly elevated (29.79 +/- 2.92 %) and LGE was detected in nine cases (45 %). LGE positive carriers had lower left ventricular ejection fraction in CMR (64.36 +/- 5.78 vs. 56.67 +/- 6.89 %, p = 0.014), higher bothCK (629.89 +/- 317.48 vs. 256.18 +/- 109.10 U/l, p = 0.002) and CK-MB (22.13 +/- 5.25 vs. 12.11 +/- 2.21 U/l, p = 0.001), as well as shorter walking distances during the 6MWT (432.44 +/- 96.72 vs. 514.91 +/- 66.80 m, p = 0.037). 90.9 % of subjects without LGE had normal pro-BNP, whereas in 66.7 % of those presenting LGE pro-BNP was elevated (p = 0.027). All individuals without LGE were in the NYHA class I, whereas all those in NYHA classes II and III showed positive for LGE (p = 0.066). CONCLUSIONS: Myocardial involvement shown as LGE in CMR occurs in a substantial number of DMD carriers; it is associated with clinical and morphometric signs of incipient heart failure. LGE is thus a sensitive parameter for the early diagnosis of cardiomyopathy in DMD carriers. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01712152 Trial registration: October 19, 2012. First patient enrolled: September 27, 2012 (retrospectively registered). PMID- 27660109 TI - Choosing the right protein A affinity chromatography media can remove aggregates efficiently. AB - Protein A chromatography (PAC) is commonly used as an efficient capture step in monoclonal antibody (mAb) separation processes. Usually dynamic binding capacity is used for choosing the right PAC. However, if aggregates can be efficiently removed during elution, it can make the following polishing steps easier. In this study a method for choosing the right PAC media in terms of mAb aggregate removal is proposed. Linear pH gradient elution experiments of two different mAbs on various PAC columns are carried out, where the elution behavior of aggregates as well as the monomer is measured. Aggregates of one mAb are more strongly retained compared with the mAb monomer. Another mAb showed different elution behavior, where the aggregates are eluted as both the weakly and strongly retained peaks. In order to remove the two types of aggregates by stepwise elution two protocols are tested. The first protocol A consisted of the sample loading, the wash with the equilibration buffer and the low pH elution. The wash stage of the second protocol B included the wash with 1.0 M arginine. No detectable peaks are observed during the wash stage of protocol A whereas significant peaks are monitored during the arginine wash of protocol B. One of the PAC columns showed a smaller peak during the arginine wash. In addition, both aggregate removal and monomer yield are higher with protocol B compared with the other PAC columns. This method is found to be useful for choosing the right PAC column. PMID- 27660110 TI - Performance evaluation of Mindray CAL 8000(BC-6800 and SC-120) hematology analyzer and slidemaker/stainer. AB - INTRODUCTION: The Mindray CAL 8000 is a cellular analysis line that consists of the BC-6800, an automated hematology analyzer, and the SC-120, an automated slidemaker/stainer. We evaluated the performances of the BC-6800 and the SC-120. METHODS: Four hundred and eight normal and abnormal samples were analyzed. The performance of the BC-6800 and Sysmex XE-2100 were compared, and blood films by the SC-120 and manual method were compared according to the CLSI guideline H26-A2 and H20-A2. RESULTS: Most parameters measured by the BC-6800 matched well with the XE-2100 and manual differential. The flag efficiency of the BC-6800 for blasts (95.3%) and atypical lymphocytes (92.6%) were higher while immature granulocytes (89.7%) and NRBCs (94.1%) were lower than that of the XE-2100. Additionally, the BC-6800 detected four of five samples infected with plasmodium parasites. The SC-120 showed no carry-over and expected repeatability. There was good agreement on the five-part differential including abnormal cells between blood films by the SC-120 and manually prepared blood films. The shape of the RBC was also comparable between blood films. CONCLUSION: The CAL-8000 analysis line is beneficial for precise, fast hematology work, and even more useful in malaria endemic areas. PMID- 27660113 TI - Stress in Portuguese Middle School Transition: A Multilevel Analysis. AB - Transition from elementary to middle school is commonly seen as a period of stress, impacting students' school adjustment. The present longitudinal study aimed to analyze the difference in stress levels between the end of 4th grade and 5th grade, while also analyzing gender differences and 5th grade retention. Two hundred fifty-eight 4th grade students (M age = 9.55; SD = 0.77) from six Portuguese public schools, from the municipality of Torres Vedras, participated in this study. Self-report questionnaires were administered at the end of the 4th and 5th grades, and 5th grade school records were also collected. Results showed that 5th graders present higher levels of Academic Stress (d = .29) and Teacher/Rules Stress (d = .28). Girls had a greater increase of Peer-related Stress with the transition (p < .01). Students who were retained at the end of 5th grade showed higher increases of Teacher/Rules Stress (p < .05). Intervention programs that aim to support the transition from elementary to middle school are needed, in order to reduce the increase of stress levels at 5th grade and to promote a better school adjustment in the first year of middle school. PMID- 27660112 TI - Tobacco retail outlet restrictions: health and cost impacts from multistate life table modelling in a national population. AB - BACKGROUND: Since there is some evidence that the density and distribution of tobacco retail outlets may influence smoking behaviours, we aimed to estimate the impacts of 4 tobacco outlet reduction interventions in a country with a smoke free goal: New Zealand (NZ). METHODS: A multistate life-table model of 16 tobacco related diseases, using national data by sex, age and ethnicity, was used to estimate quality-adjusted life years (QALYs) gained and net costs over the remainder of the 2011 NZ population's lifetime. The outlet reduction interventions assumed that increased travel costs can be operationalised as equivalent to price increases in tobacco. RESULTS: All 4 modelled interventions led to reductions of >89% of current tobacco outlets after the 10-year phase-in process. The most effective intervention limited sales to half of liquor stores (and nowhere else) at 129 000 QALYs gained over the lifetime of the population (95% UI: 74 100 to 212 000, undiscounted). The per capita QALY gains were up to 5 times greater for Maori (indigenous population) compared to non-Maori. All interventions were cost-saving to the health system, with the largest saving for the liquor store only intervention: US$1.23 billion (95% UI: $0.70 to $2.00 billion, undiscounted). CONCLUSIONS: These tobacco outlet reductions reduced smoking prevalence, achieved health gains and saved health system costs. Effects would be larger if outlet reductions have additional spill-over effects (eg, smoking denormalisation). While these interventions were not as effective as tobacco tax increases (using the same model), these and other strategies could be combined to maximise health gain and to maximise cost-savings to the health system. PMID- 27660111 TI - Vaping on Instagram: cloud chasing, hand checks and product placement. AB - INTRODUCTION: This study documented images posted on Instagram of electronic cigarettes (e-cigarette) and vaping (activity associated with e-cigarette use). Although e-cigarettes have been studied on Twitter, few studies have focused on Instagram, despite having 500 million users. Instagram's emphasis on images warranted investigation of e-cigarettes, as past tobacco industry strategies demonstrated that images could be used to mislead in advertisements, or normalise tobacco-related behaviours. Findings should prove informative to tobacco control policies in the future. METHODS: 3 months of publicly available data were collected from Instagram, including images and associated metadata (n=2208). Themes of images were classified as (1) activity, for example, a person blowing vapour; (2) product, for example, a personal photo of an e-cigarette device; (3) advertisement; (4) text, for example, 'meme' or image containing mostly text and (5) other. User endorsement (likes) of each type of image was recorded. Caption text was analysed to explore different trends in vaping and e-cigarette-related text. RESULTS: Analyses found that advertisement-themed images were most common (29%), followed by product (28%), and activity (18%). Likes were more likely to accompany activity and product-themed images compared with advertisement or text themed images (p<0.01). Vaping-related text greatly outnumbered e-cigarette related text in the image captions. CONCLUSIONS: Instagram affords its users the ability to post images of e-cigarette-related behaviours and gives advertisers the opportunity to display their product. Future research should incorporate novel data streams to improve public health surveillance, survey development and educational campaigns. PMID- 27660114 TI - The impact of an 8-year mass drug administration programme on prevalence, intensity and co-infections of soil-transmitted helminthiases in Burundi. AB - BACKGROUND: Soil-transmitted helminth (STH) infections are amongst the most prevalent infections in the world. Mass drug administration (MDA) programmes have become the most commonly used national interventions for endemic countries to achieve elimination. This paper aims to describe the effect of an 8-year MDA programme on the prevalence, intensity of infection and co-infection of STH in Burundi from 2007 to 2014 and critically appraise the trajectory towards STH elimination in the country. RESULTS: Annual STH parasitological surveys (specifically, a "pilot study" from 2007 to 2011, an "extension study" from 2008 to 2011, and a "national reassessment" in 2014; n = 27,658 children), showed a significant drop in prevalence of infection with any STH ("pooled STH") between baseline and 2011 in both studies, falling from 32 to 16 % in the pilot study, and from 35 to 16 % in the extension study. Most STH infections were of low intensity according to WHO classification. The national reassessment in 2014 showed that prevalence of pooled STH remained significantly below the prevalence in 2007 in both studies but there was no further decrease in STH prevalence from 2011 levels during this time. Spatial dependence analysis showed that prevalence of Trichuris trichiura and Ascaris lumbricoides had a tendency to cluster over the years, whilst only trends in spatial dependence were evident for hookworm infections. Spatial dependence fluctuated over the course of the programme for Ascaris lumbricoides and Trichuris trichiura. However, spatial trends in spatial dependence were evident in 2010 for Ascaris lumbricoides. Analysis of spatial clustering of intensity of infection and heavy infections revealed that the intensity changed over time for all parasites. Heavy intensity was only evident in Ascaris lumbricoides for 2008 and did not appear in proceeding years and other parasites. CONCLUSIONS: These results demonstrate that sustained annual MDA significantly reduced the prevalence of STH infection in school-age children but was unable to achieve elimination. Additionally, significant decline in prevalence was accompanied by a drop in spatial clustering of infection indicators across all sites from 2008. The lack of consistency in the results of the spatial dependence analysis highlights that MDA programmes can interrupt the normal transmission dynamics of STH parasites. PMID- 27660115 TI - Equivalent seminal characteristics in human and stallion at first and second ejaculated fractions. AB - Sperm quality was assessed in normozoospermic human (n = 10) and Spanish breed stallion (n = 10) after sperm fractionation during ejaculation. The first ejaculated fraction was separated from the second. A third sample was reconstituted using equivalent proportion of both fractions (RAW). Fraction 1, Fraction 2 and RAW semen were incubated for 30 min at 37 degrees C to homogenise the impact of iatrogenic damage between both species. Sperm concentration, motility and sperm DNA damage were assessed in each fraction and RAW semen. The results showed two important facts: (i) spermatozoa confined at Fraction 1 exhibit superior parameters than those included at Fraction 2 in both species, and (ii) there is a certain level of concordance between species in the proportion of benefit observed when Fraction 1 is compared to RAW semen. Altogether, these results call into question whether the standard practice of whole ejaculate collection can be considered the best strategy when using male gametes for artificial insemination. In fact, the reconstituted RAW semen exhibits poorer semen characteristics than those found in Fraction 1. PMID- 27660116 TI - The effect of declining exposure on T cell-mediated immunity to Plasmodium falciparum - an epidemiological "natural experiment". AB - BACKGROUND: Naturally acquired immunity to malaria may be lost with lack of exposure. Recent heterogeneous reductions in transmission in parts of Africa mean that large populations of previously protected people may lose their immunity while remaining at risk of infection. METHODS: Using two ethnically similar long term cohorts of children with historically similar levels of exposure to Plasmodium falciparum who now experience very different levels of exposure, we assessed the effect of decreased parasite exposure on antimalarial immunity. Peripheral blood mononuclear cells (PBMCs) from children in each cohort were stimulated with P. falciparum and their P. falciparum-specific proliferative and cytokine responses were compared. RESULTS: We demonstrate that, while P. falciparum-specific CD4+ T cells are maintained in the absence of exposure, the proliferative capacity of these cells is altered considerably. P. falciparum specific CD4+ T cells isolated from children previously exposed, but now living in an area of minimal exposure ("historically exposed") proliferate significantly more upon stimulation than cells isolated from children continually exposed to the parasite. Similarly, PBMCs from historically exposed children expressed higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines after stimulation with P. falciparum. Notably, we found a significant positive association between duration since last febrile episode and P. falciparum-specific CD4+ T cell proliferation, with more recent febrile episodes associated with lower proliferation. CONCLUSION: Considered in the context of existing knowledge, these data suggest a model explaining how immunity is lost in absence of continuing exposure to P. falciparum. PMID- 27660119 TI - 2016 Presidential Address: Diabetes at 212 degrees -Confronting the Invisible Disease. AB - This address was delivered by Desmond Schatz, MD, President, Medicine & Science, of the American Diabetes Association (ADA), at the Association's 76th Scientific Sessions in New Orleans, LA, on 12 June 2016. Dr. Schatz is Professor and Associate Chairman of Pediatrics, Medical Director of the University of Florida Diabetes Institute, and Director of the Clinical Research Center at the University of Florida, Gainesville, FL. A physician-scientist, he has been involved in type 1 diabetes research since the mid-1980s and has published over 300 articles and book chapters. Dr. Schatz's research focuses on the prediction, natural history, genetics, immunopathogenesis, and prevention of type 1 diabetes, as well as the treatment of children and adolescents with type 1 diabetes. He is the principal investigator on several National Institutes of Health, JDRF, and other competitively funded grants. Dr. Schatz earned his medical degree from the University of the Witwatersrand School of Medicine in Johannesburg, South Africa, and completed his residency and fellowship at the University of Florida. He has been an ADA volunteer for over 30 years and has served on the Professional Practice Committee (twice), Scientific Sessions Meeting Planning Committee, Publications Policy Committee (Chair), Government Relations Committee, Youth Strategies Committee, and Board of Directors. A board-certified pediatric endocrinologist, Dr. Schatz is the 2016 recipient of the Banting Medal for Leadership and Service from the ADA for his outstanding commitment and contributions to the Association. PMID- 27660117 TI - Nail features in healthy term newborns: a single-centre observational study of 52 cases. AB - INTRODUCTION: The anatomy and embryology of the nail are well known, and nail abnormalities are a feature of many genodermatoses. However, the physiological aspect is not well described. We aimed to analyse the physiological features of nails in healthy newborns. METHODS: We performed an observational, prospective study at University Hospital Center of Tours between July and October 2015. Newborns were included by a dermatologist assistant during the systematic examination on release of the mother from the hospital. The medical history of the mother and infant were recorded by using a standardized questionnaire. Finger and toenails were systematically photographed for a second interpretation by a dermatologist with blinding to the first photograph. RESULTS: Fifty-eight patients were eligible, and 52 were included. Half of the newborns were males, and the mean age at inclusion was 3.6 +/- 1.2 days. Fingernails had an oval shape (71.1%) or a flat curvature (63.5%), and half had a lunula. Toenails showed an apparent hypertrophy of the proximal nail fold (38.4%) and lateral nail fold (73.1%). The shape of the nails was triangular (50.0%) or round (21.1%). We noted koilonychia in 32.7% of infants and lunula in 7.7%. Distal parts showed onychoschizia (28.8%) and onycholysis (26.9%). CONCLUSION: Koilonychia, onychoschizia of toenails or absence of lunula are physiological features of nails in newborns. PMID- 27660120 TI - Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study. AB - OBJECTIVE: Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. RESEARCH DESIGN AND METHODS: Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 +/- 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order. RYGB subjects repeated the studies with somatostatin infusion and basal insulin replacement. Fullness, sickness, and postscan ad libitum meal consumption were measured. Regional brain FDG uptake was compared using statistical parametric mapping. RESULTS: RYGB subjects had higher overall fullness and food-induced sickness and lower ad libitum consumption. Brain responses to eating differed in the hypothalamus and pituitary (exaggerated activation in RYGB), left medial orbital cortex (OC) (activation in RYGB, deactivation in NW), right dorsolateral frontal cortex (deactivation in RYGB and NW, absent in Ob), and regions mapping to the default mode network (exaggerated deactivation in RYGB). Somatostatin in RYGB reduced postprandial gut peptide responses, sickness, and medial OC activation. CONCLUSIONS: RYGB induces weight loss by augmenting normal brain responses to eating in energy balance regions, restoring lost inhibitory control, and altering hedonic responses. Altered postprandial gut peptide responses primarily mediate changes in food-induced sickness and OC responses, likely to associate with food avoidance. PMID- 27660121 TI - A Common Gene Variant in Glucokinase Regulatory Protein Interacts With Glucose Metabolism on Diabetic Dyslipidemia: the Combined CODAM and Hoorn Studies. AB - OBJECTIVE: Small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP) are potential new glucose-lowering targets. They stimulate hepatic glucose disposal by increasing glucokinase activity in the liver. It can, however, be anticipated that increased hepatic glucokinase activity might be accompanied by the development of hypertriglyceridemia, particularly in type 2 diabetes. We examined whether the strength of association between rs1260326, a common, functional gene variant in GKRP, and plasma lipids is affected by glucose metabolism. RESEARCH DESIGN AND METHODS: rs1260326 was genotyped in subjects with normal glucose metabolism (n = 497), subjects with impaired glucose metabolism (n = 256), and patients with type 2 diabetes (n = 351) in the combined Hoorn and Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) studies. RESULTS: The strength of association between the rs1260326 minor T allele and plasma triglycerides increased from normal glucose metabolism to impaired glucose metabolism to type 2 diabetes (P for interaction = 0.002). The inverse relation between rs1260326 and plasma HDL cholesterol was again most prominent in type 2 diabetes (P for interaction = 0.004). Similar trends were observed when the Hoorn and CODAM cohorts were analyzed separately. Comparable results were obtained when glucose metabolism strata were replaced by continuous indices of glucose metabolism, i.e., HbA1c and fasting plasma glucose. CONCLUSIONS: These findings illustrate that common gene variants, such as rs1260326, can have substantial effect sizes when they are studied in specific populations, such as type 2 diabetes. Moreover, our results shed light on potential side effects of small molecule disruptors of the GKRP-glucokinase complex, especially when glucose control is suboptimal. PMID- 27660123 TI - Erratum. Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes. PMID- 27660122 TI - Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities. AB - Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator-activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium. PMID- 27660125 TI - Effect of Regular Exercise Commenced in Early Pregnancy on the Incidence of Gestational Diabetes Mellitus in Overweight and Obese Pregnant Women: A Randomized Controlled Trial. PMID- 27660126 TI - Comment on Narayan. Type 2 Diabetes: Why We Are Winning the Battle but Losing the War? 2015 Kelly West Award Lecture. Diabetes Care 2016;39:653-663. PMID- 27660127 TI - Response to Comment on Narayan. Type 2 Diabetes: Why We Are Winning the Battle but Losing the War? 2015 Kelly West Award Lecture. Diabetes Care 2016;39:653-663. PMID- 27660128 TI - Comment on Almurdhi et al. Reduced Lower-Limb Muscle Strength and Volume in Patients With Type 2 Diabetes in Relation to Neuropathy, Intramuscular Fat, and Vitamin D Levels. Diabetes Care 2016;39:441-447. PMID- 27660129 TI - Response to Comment on Almurdhi et al. Reduced Lower-Limb Muscle Strength and Volume in Patients With Type 2 Diabetes in Relation to Neuropathy, Intramuscular Fat, and Vitamin D Levels. Diabetes Care 2016;39:441-447. PMID- 27660130 TI - Comment on the FLAT-SUGAR Trial Investigators. Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP 1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. Diabetes Care 2016;39:973-981. PMID- 27660131 TI - Response to Comment on the FLAT-SUGAR Trial Investigators. Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. Diabetes Care 2016;39:973-981. PMID- 27660132 TI - Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424-1430. PMID- 27660133 TI - Response to Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424-1430. PMID- 27660134 TI - Comment on Rickels et al. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care 2016;39:264-270. PMID- 27660136 TI - Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation. AB - Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. PMID- 27660135 TI - Response to Comment on Rickels et al. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care 2016;39:264-270. PMID- 27660137 TI - In Vivo 3-Dimensional Radiopharmaceutical-Excited Fluorescence Tomography. AB - : Cerenkov luminescence imaging can image radiopharmaceuticals using a high sensitivity charge-coupled device camera. However, Cerenkov luminescence emitted from the radiopharmaceuticals is weak and has low penetration depth in biologic tissues, which severely limits the sensitivity and accuracy of Cerenkov luminescence imaging. This study presents 3-dimensional (3D) radiopharmaceutical excited fluorescence tomography (REFT) using europium oxide (EO) nanoparticles, which enhances the Cerenkov luminescence signal intensity, improves the penetration depth, and obtains more accurate 3D distribution of radiopharmaceuticals. METHODS: The enhanced optical signals of various radiopharmaceuticals (including Na131I, 18F-FDG, 68GaCl3, Na99mTcO4) by EO nanoparticles were detected in vitro. The location and 3D distribution of the radiopharmaceuticals of REFT were then reconstructed and compared with those of Cerenkov luminescence tomography through the experiments with the phantom, artificial source-implanted mouse models, and mice bearing hepatocellular carcinomas. RESULTS: The mixture of 68GaCl3 and EO nanoparticles possessed the strongest optical signals compared with the other mixtures. The in vitro phantom and implanted mouse studies showed that REFT revealed more accurate 3D distribution of 68GaCl3 REFT can detect more tumors than small-animal PET in hepatocellular carcinoma-bearing mice and achieved more accurate 3D distribution information than Cerenkov luminescence tomography. CONCLUSION: REFT with EO nanoparticles significantly improves accuracy of localization of radiopharmaceuticals and can precisely localize the tumor in vivo. PMID- 27660138 TI - Radiation Dosimetry for 177Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions. AB - Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using 177Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys (Ahx)-[68Ga(HBEDCC)] (68Ga-PSMA-HBED-CC) PET. Methods: A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic 68Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. Results: The mean whole-body effective dose for all cycles was 0.06 +/- 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 +/- 0.21 Gy/GBq for the kidneys; 0.12 +/- 0.06 Gy/GBq for the liver; and 0.55 +/- 0.14 Gy/GBq for the parotid, 0.64 +/- 0.40 Gy/GBq for the submandibular, and 3.8 +/- 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 +/- 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 +/- 2.9 Gy/GBq for the first, 3.3 +/- 2.5 Gy/GBq for the second, 2.7 +/- 2.3 Gy/GBq for the third, and 2.4 +/- 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r = 0.44, P < 0.001 for SUVmax; r = 0.43, P < 0.001 for SUVmean) and moderately correlated with the change of SUV (r = 0.478, P < 0.001 for SUVmax, and r = 0.50, P < 0.001 for SUVmean). Conclusion: Organ- and tumor absorbed doses for 177Lu-PSMA I&T are comparable to recent reports and complement these with information on an excellent correlation between the 4 therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq of 177Lu-PSMA I&T appears to be safe and justifiable. The correlation between pretherapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET imaging for patient selection. PMID- 27660140 TI - Reply: THYROPET Study: Is It Biology or Technology That Is the Issue? PMID- 27660141 TI - Correlation Between SUVmax and CT Radiomic Analysis Using Lymph Node Density in PET/CT-Based Lymph Node Staging. AB - : In patients with lung cancer (LC), malignant melanoma (MM), gastroenteropancreatic neuroendocrine tumors (GEP NETs), and prostate cancer (PCA), lymph node (LN) staging is often performed by 18F-FDG PET/CT (LC and MM), 68Ga-DOTATOC PET/CT (GEP NET), and 68Ga-labeled prostate-specific membrane antigen PET/CT (PCA) but is sometimes not accurate because of indeterminate PET findings. To better evaluate malignant LN infiltration, additional surrogate parameters, especially in cases with indeterminate PET findings, would be helpful. The purpose of this study was to evaluate whether SUVmax in the PET examination might correlate with semiautomated density measurements of LNs in the CT component of the PET/CT examination. METHODS: After approval by the institutional review board, 1,022 LNs in the PET/CT examinations of 148 patients were retrospectively analyzed (LC: 327 LNs of 40 patients; MM: 224 LNs of 33 patients; GEP NET: 217 LNs of 35 patients; and PCA: 254 LNs of 40 patients). PET/CT was performed before surgery, biopsy, chemotherapy, or internal or external radiation therapy, according to the clinical schedule; patients with prior chemotherapy or radiation therapy were excluded. SUVmax analyses were based on uptake 60 min after tracer injection, and volumetric CT histogram analyses were based on the unenhanced CT images of the PET/CT scan. RESULTS: PET findings were considered positive or negative on the basis of SUVmax in the LN compared with that in the blood pool; histologic confirmation was not available. Of the 1,022 LNs, 331 were PET-positive (3 times the SUVmax of the blood pool), 86 were PET-indeterminate (1-3 times the SUVmax of the blood pool), and 605 were PET negative (less than the SUVmax of the blood pool). PET-positive LNs had significantly higher CT densities than PET-negative LNs, irrespective of the type of cancer. CONCLUSION: CT density measurements of LNs in patients with LC, MM, GEP NET, and PCA correlated with18F-FDG uptake, 68Ga-DOTATOC uptake, and 68Ga PSMA uptake, respectively, and might therefore serve as an additional surrogate parameter for differentiating between malignant and benign LNs. The use of a 7.5 Hounsfield unit CT density threshold to differentiate between malignant and benign LN infiltration and 20 Hounsfield units to exclude benign LN processes might be possible in clinical routine and would be especially helpful for PET indeterminate LNs. PMID- 27660139 TI - 68Ga-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience. AB - : The purpose of this work was to evaluate the effect of androgen receptor (AR) inhibition on prostate-specific membrane antigen (PSMA) uptake imaged using 68Ga PSMA-11 PET in a mouse xenograft model and in a patient with castration-sensitive prostate cancer. METHODS: We imaged 3 groups of 4 mice bearing LNCaP-AR xenografts before and 7 d after treatment with ARN-509, orchiectomy, or control vehicle. Additionally, we imaged one patient with castration-sensitive prostate cancer before and 4 wk after treatment with androgen deprivation therapy (ADT). Uptake on pre- and posttreatment imaging was measured and compared. RESULTS: PSMA uptake increased 1.5- to 2.0-fold in the xenograft mouse model after treatment with both orchiectomy and ARN-509 but not with vehicle. Patient imaging demonstrated a 7-fold increase in PSMA uptake after the initiation of ADT. Thirteen of 22 lesions in the imaged patient were visualized on PSMA PET only after treatment with ADT. CONCLUSION: Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effect seen in cell and animal models can be recapitulated in humans. A better understanding of the temporal changes in PSMA expression is needed to leverage this effect for both improved diagnosis and improved therapy. PMID- 27660143 TI - Reply: The Ongoing Misperception That Labeled Leukocyte Imaging Is Superior to 18F-FDG PET for Diagnosing Prosthetic Joint Infection. PMID- 27660142 TI - Parametric Methods for Dynamic 11C-Phenytoin PET Studies. AB - In this study, the performance of various methods for generating quantitative parametric images of dynamic 11C-phenytoin PET studies was evaluated. Methods: Double-baseline 60-min dynamic 11C-phenytoin PET studies, including online arterial sampling, were acquired for 6 healthy subjects. Parametric images were generated using Logan plot analysis, a basis function method, and spectral analysis. Parametric distribution volume (VT) and influx rate (K1) were compared with those obtained from nonlinear regression analysis of time-activity curves. In addition, global and regional test-retest (TRT) variability was determined for parametric K1 and VT values. Results: Biases in VT observed with all parametric methods were less than 5%. For K1, spectral analysis showed a negative bias of 16%. The mean TRT variabilities of VT and K1 were less than 10% for all methods. Shortening the scan duration to 45 min provided similar VT and K1 with comparable TRT performance compared with 60-min data. Conclusion: Among the various parametric methods tested, the basis function method provided parametric VT and K1 values with the least bias compared with nonlinear regression data and showed TRT variabilities lower than 5%, also for smaller volume-of-interest sizes (i.e., higher noise levels) and shorter scan duration. PMID- 27660144 TI - Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects. AB - 18F-T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurologic disorders including Alzheimer disease and traumatic brain injury (TBI). The current study characterizes 18F-T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions. Methods: Nine subjects (4 controls, 3 with a history of TBI, 2 with mild cognitive impairment due to suspected Alzheimer disease) underwent dynamic PET imaging for up to 120 min after bolus injection of 18F-T807 with arterial blood sampling. Total volume of distribution (VT) was estimated using compartmental modeling (1- and 2-tissue configurations) and graphical analysis techniques (Logan and multilinear analysis 1 [MA1] regression methods). Reference region-based methods of quantification were explored including Logan distribution volume ratio (DVR) and static SUV ratio (SUVR) using the cerebellum as a reference tissue. Results: The percentage of unmetabolized 18F-T807 in plasma followed a single exponential with a half-life of 17.0 +/- 4.2 min. Metabolite corrected plasma radioactivity concentration fit a biexponential (half-lives, 18.1 +/- 5.8 and 2.4 +/- 0.5 min). 18F-T807 in gray matter peaked quickly (SUV > 2 at ~5 min). Compartmental modeling resulted in good fits, and the 2-tissue model with estimated blood volume correction (2Tv) performed best, particularly in regions with elevated binding. VT was greater in mild cognitive impairment subjects than controls in the occipital, parietal, and temporal cortices as well as the posterior cingulate gyrus, precuneus, and mesial temporal cortex. High focal uptake was found in the posterior corpus callosum of a TBI subject. Plots from Logan and MA1 graphical methods became linear by 30 min, yielding regional estimates of VT in excellent agreement with compartmental analysis and providing high-quality parametric maps when applied in voxelwise fashion. Reference region based approaches including Logan DVR (t* = 55 min) and SUVR (80- to 100-min interval) were highly correlated with DVR estimated using 2Tv (R2 = 0.97, P < 0.0001). Conclusion:18F-T807 showed rapid clearance from plasma and properties suitable for tau quantification with PET. Furthermore, simplified approaches using DVR (t* = 55 min) and static SUVR (80-100 min) with cerebellar reference tissue were found to correlate highly with compartmental modeling outcomes. PMID- 27660145 TI - Biodistribution and Radiation Dosimetry of 11C-Nicotine from Whole-Body PET Imaging in Humans. AB - This study assessed the in vivo distribution of 11C-nicotine and the absorbed radiation dose from whole-body 11C-nicotine PET imaging of 11 healthy (5 male and 6 female) subjects. Methods: After an initial CT attenuation scan, 11C-nicotine was administered via intravenous injection. A dynamic PET scan was acquired for 90 s with the brain in the field of view, followed by a series of 13 whole-body PET scans acquired over a 90-min period. Regions of interest were drawn over organs visible in the reconstructed PET images. Time-activity curves were generated, and the residence times were calculated. The absorbed radiation dose for the whole body was calculated by entering the residence time in OLINDA/EXM 1.0 software to model the equivalent organ dose and the effective dose for a 70 kg man. Results: The mean residence times for 11C-nicotine in the liver, red marrow, brain, and lungs were 0.048 +/- 0.010, 0.031 +/- 0.005, 0.021 +/- 0.004, and 0.020 +/- 0.005 h, respectively. The mean effective dose for 11C-nicotine was 5.44 +/- 0.67 MUSv/MBq. The organs receiving the highest absorbed dose from the 11C-nicotine injection were the urinary bladder wall (14.68 +/- 8.70 MUSv/MBq), kidneys (9.56 +/- 2.46 MUSv/MBq), liver (8.94 +/- 1.67 MUSv/MBq), and spleen (9.49 +/- 3.89 MUSv/MBq). The renal and hepatobiliary systems were the major clearance and excretion routes for radioactivity. Conclusion: The estimated radiation dose from 11C-nicotine administration is relatively modest and would allow for multiple PET examinations on the same subject. PMID- 27660146 TI - Monte Carlo N-Particle (MCNP) Modeling of the Cellular Dosimetry of 64Cu: Comparison with MIRDcell S Values and Implications for Studies of Its Cytotoxic Effects. AB - : 64Cu emits positrons as well as beta- particles and Auger and internal conversion electrons useful for radiotherapy. Our objective was to model the cellular dosimetry of 64Cu under different geometries commonly used to study the cytotoxic effects of 64Cu. METHODS: Monte Carlo N-Particle (MCNP) was used to simulate the transport of all particles emitted by 64Cu from the cell surface (CS), cytoplasm (Cy), or nucleus (N) of a single cell; monolayer in a well (radius = 0.32-1.74 cm); or a sphere (radius = 50-6,000 MUm) of cells to calculate S values. The radius of the cell and N ranged from 5 to 12 MUm and 2 to 11 MUm, respectively. S values were obtained by MIRDcell for comparison. MCF7/HER2-18 cells were exposed in vitro to 64Cu-labeled trastuzumab. The subcellular distribution of 64Cu was measured by cell fractionation. The surviving fraction was determined in a clonogenic assay. RESULTS: The relative differences of MCNP versus MIRDcell self-dose S values (Sself) for 64Cu ranged from -0.2% to 3.6% for N to N (SN<-N), 2.3% to 8.6% for Cy to N (SN<-Cy), and 12.0% to 7.3% for CS to N (SN<-CS). The relative differences of MCNP versus MIRDcell cross-dose S values were 25.8%-30.6% for a monolayer and 30%-34% for a sphere, respectively. The ratios of SN<-N versus SN<-Cy and SN<-Cy versus SN<-CS decreased with increasing ratio of the N of the cell versus radius of the cell and the size of the monolayer or sphere. The surviving fraction of MCF7 /: HER2 18 cells treated with 64Cu-labeled trastuzumab (0.016-0.368 MBq/MUg, 67 nM) for 18 h versus the absorbed dose followed a linear survival curve with alpha = 0.51 +/- 0.05 Gy-1 and R2 = 0.8838. This is significantly different from the linear quadratic survival curve of MCF7 /: HER2-18 cells exposed to gamma-rays. CONCLUSION: MCNP- and MIRDcell-calculated S values agreed well. 64Cu in the N increases the dose to the N in isolated single cells but has less effect in a cell monolayer or small cluster of cells simulating a micrometastasis, and little effect in a sphere analogous to a tumor xenograft compared with 64Cu in the Cy or on the CS. The dose deposited by 64Cu is less effective for cell killing than gamma-rays. PMID- 27660147 TI - Head-to-Head Comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: A Prospective Study of 59 Patients with Neuroendocrine Tumors. AB - Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up, and treatment planning of neuroendocrine tumor (NET). PET-based tracers using 68Ga as the radioisotope have in most centers replaced SPECT-based tracers as the gold standard. 64Cu-DOTATATE is a new PET tracer that has been shown to be far superior to the SPECT tracer 111In-diethylenetriaminepentaacetic acid-octreotide. Because of the advantages of 64Cu over 68Ga, we hypothesized that the tracer has a higher sensitivity than 68Ga-based tracers. To test this hypothesis, we compared on a head-to-head basis the diagnostic performance of 64Cu-DOTATATE with that of 68Ga-DOTATOC in NET patients. Methods: Fifty-nine NET patients were scanned with both 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT and compared on a head-to head basis. Discordant lesions were verified during at least 30 mo of follow-up. Results: A total of 701 lesions were concordantly detected on both 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT scans, whereas an additional 68 lesions were found by only one of the scans. 64Cu-DOTATATE showed 42 lesions not found on 68Ga-DOTATOC, of which 33 were found to be true-positive on follow-up. 68Ga-DOTATOC showed 26 lesions not found on 64Cu-DOTATATE, of which 7 were found to be true-positive on follow-up. False-positives were mainly lymph node lesions. Accordingly, 83% of the additional true lesions found on only one of the scans were found by 64Cu DOTATATE. On a patient-basis, additional true lesions were found by 64Cu-DOTATATE and 68Ga-DOTATOC in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusion:64Cu-DOTATATE has advantages over 68Ga-DOTATOC in the detection of lesions in NET patients. Although patient-based sensitivity was the same for 64Cu-DOTATATE and 68Ga DOTATOC in this cohort, significantly more lesions were detected by 64Cu DOTATATE. Furthermore, the shelf life of more than 24 h and the scanning window of at least 3 h make 64Cu-DOTATATE favorable and easy to use in the clinical setting. PMID- 27660148 TI - 68Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with 223Ra: Proof of Concept. AB - We retrospectively evaluated the utility of 68Ga-PSMA-11 PET for planning 223RaCl2 therapy of patients with metastatic prostate cancer and its impact on the therapeutic response as determined by prostate-specific antigen (PSA) and alkaline phosphatase (ALP), as well as the correlation of PSA changes with the results of prostate-specific membrane antigen (PSMA) PET follow-up scans. Methods: Sixty-three patients with a median age of 73 y who underwent 307 cycles of therapy with 223RaCl2 were analyzed. In 31 patients, bone scanning and radiologic imaging were performed for pretherapeutic imaging (group 1). In 32 patients, bone scanning and PSMA PET were performed before therapy (group 2). Patients with small lymph node metastases and local recurrence were not excluded from treatment, consistent with current guidelines. PSA and ALP were measured before each treatment cycle and 4 wk after the final cycle. Thirteen patients from group 2, who underwent a second PSMA PET scan as a follow-up, were evaluated to determine the significance of PSA changes as a follow-up marker. Results: In group 1, 4 patients (12.9%) showed a PSA decline, of whom 2 patients and 1 patient showed a PSA decline of more than 30% and more than 50%, respectively. In contrast, in group 2, 14 patients (43.8%) showed a PSA decline, of whom 10 and 8 patients showed a decline of more than 30% and more than 50%, respectively (P = 0.007). Thirty-seven patients had a high ALP level (19 from group 1 and 18 from group 2). Twelve (63.2%) and 16 (88.9%) patients in groups 1 and 2, respectively, showed an ALP decline. This difference was not significant; however, 7 (36%) and 13 (72.2%) patients in groups 1 and 2, respectively, showed an ALP decline of more than 30% (P = 0.04). Considering any ALP decline as a response, no patient with increasing ALP showed a PSA response (P = 0.036). There was a significant correlation between the PSA changes and the therapeutic response according to follow-up PSMA PET. Conclusion: When PSMA PET is used as the gatekeeper in addition to bone scanning, radionuclide therapy with 223Ra may be more effective and have more success regarding changes in the PSA. An increase in PSA during therapy cycles occurs because of disease progression. PMID- 27660149 TI - Filling gaps on ivermectin knowledge: effects on the survival and reproduction of Anopheles aquasalis, a Latin American malaria vector. AB - BACKGROUND: Strategies designed to advance towards malaria elimination rely on the detection and treatment of infections, rather than fever, and the interruption of malaria transmission between mosquitoes and humans. Mass drug administration with anti-malarials directed at eliminating parasites in blood, either to entire populations or targeting only those with malaria infections, are considered useful strategies to progress towards malaria elimination, but may be insufficient if applied on their own. These strategies assume a closer contact with populations, so incorporating a vector control intervention tool to those approaches could significantly enhance their efficacy. Ivermectin, an endectocide drug efficacious against a range of Anopheles species, could be added to other drug-based interventions. Interestingly, ivermectin could also be useful to target outdoor feeding and resting vectors, something not possible with current vector control tools, such as impregnated bed nets or indoor residual spraying (IRS). RESULTS: Anopheles aquasalis susceptibility to ivermectin was assessed. In vivo assessments were performed in six volunteers, being three men and three women. The effect of ivermectin on reproductive fitness and mosquito survivorship using membrane feeding assay (MFA) and direct feeding assay (DFA) was assessed and compared. The ivermectin lethal concentration (LC) values were LC50 = 47.03 ng/ml [44.68-49.40], LC25 = 31.92 ng/ml [28.60-34.57] and LC5 = 18.28 ng/ml [14.51-21.45]. Ivermectin significantly reduced the survivorship of An. aquasalis blood-fed 4 h post-ingestion (X 2 [N = 880] = 328.16, p < 0.001), 2 days post ingestion (DPI 2) (X 2 [N = 983] = 156.75, p < 0.001), DPI 7 (X 2 [N = 935] = 31.17, p < 0.001) and DPI 14 (X 2 [N = 898] = 38.63, p < 0.001) compared to the blood fed on the untreated control. The average number of oviposited eggs per female was significantly lower in LC5 group (22.44 [SD = 3.38]) than in control (34.70 [SD = 12.09]) (X 2 [N = 199] = 10.52, p < 0.001) as well as the egg hatch rate (LC5 = 74.76 [SD = 5.48]) (Control = 81.91 [SD = 5.92]) (X 2 [N = 124] = 64.24, p < 0.001). However, no differences were observed on the number of pupae that developed from larvae (Control = 34.19 [SD = 10.42) and group (LC5 = 33.33 [SD = 11.97]) (X 2 [N = 124] = 0.96, p > 0.05). CONCLUSIONS: Ivermectin drug reduces mosquito survivorship when blood fed on volunteer blood from 4 h to 14 days post-ingestion controlling for volunteers' gender. Ivermectin at mosquito sub-lethal concentrations (LC5) reduces fecundity and egg hatch rate but not the number of pupae that developed from larvae. DFA had significantly higher effects on mosquito survival compared to MFA. The findings are presented and discussed through the prism of malaria elimination in the Amazon region. PMID- 27660151 TI - Erratum to: Genotype distribution-based inference of collective effects in genome wide association studies: insights to age-related macular degeneration disease mechanism. PMID- 27660150 TI - The Perceptual Characteristics of Sodium Chloride to Sodium-Depleted Rats. AB - Three experiments assessed potential changes in the rat's perception of sodium chloride (NaCl) during a state of sodium appetite. In Experiment 1, sodium sufficient rats licking a range of NaCl concentrations (0.028-0.89M) in 15s trials showed an inverted U-shaped concentration response function peaking at 0.281M. Depleted rats (furosemide) showed an identical function, merely elevated, suggesting altered qualitative or hedonic perception but no change in perceived intensity. In Experiment 2, sodium-depleted rats were tested with NaCl, sodium gluconate, and potassium chloride (KCl; 0.028-0.89M) similar to Experiment 1. KCl was licked at the same rate as water except for a slight elevation at 0.158; sodium gluconate and NaCl were treated similarly, but rats showed more licking for hypertonic sodium gluconate than hypertonic NaCl. Sodium-depleted rats were also tested with NaCl mixed in amiloride (10-300 MUM). Amiloride reduced licking but did not alter the shape of the concentration-response function. Collectively, these results suggest that transduction of sodium by epithelial sodium channels (which are blocked by amiloride and are more dominant in sodium gluconate than NaCl transduction) is crucial for the perception of sodium during physiological sodium depletion. In Experiment 3, sodium-deplete rats were tested with NaCl as in Experiment 1 but after taste aversion conditioning to 0.3M NaCl or sucrose. Rats conditioned to avoid NaCl but not sucrose failed to express a sodium appetite, strongly suggesting that NaCl does not undergo a change in taste quality during sodium appetite-rats show no confusion between sucrose and NaCl in this paradigm. PMID- 27660152 TI - Heterogeneity of CD34 and CD38 expression in acute B lymphoblastic leukemia cells is reversible and not hierarchically organized. AB - The existence and identification of leukemia-initiating cells in adult acute B lymphoblastic leukemia (B-ALL) remain controversial. We examined whether adult B ALL is hierarchically organized into phenotypically distinct subpopulations of leukemogenic and non-leukemogenic cells or whether most B-ALL cells retain leukemogenic capacity, irrespective of their immunophenotype profiles. Our results suggest that adult B-ALL follows the stochastic stem cell model and that the expression of CD34 and CD38 in B-ALL is reversibly and not hierarchically organized. PMID- 27660155 TI - Nerve-granular cell communication in the atrium of the snail Achatina achatina occurs via the cardioexcitatory transmitters serotonin and FMRFamide. AB - In the present study, the anatomical association and functional interaction between nerve fibres and granular cells in the atrium of the snail Achatina achatina are investigated using a combination of scanning electron microscopy (SEM), pharmacological and immunofluorescence techniques. The SEM studies support a close anatomical association of axons with granular cells and new features of surface morphology are revealed. Pharmacological experiments showed that both serotonin and FMRFamide were able to induce degranulation of granular cells and the release of cysteine-rich atrial secretory protein. Serotonin- and FMRFamide immunoreactive nerve fibres were observed at variable distances from granular cells, ranging from close contact to distances as far as the diameter of a muscle bundle. These results suggest that serotonin and FMRFamide play a role as paracrine excitatory transmitters in nerve-to-granular cell communication. PMID- 27660153 TI - Comparing Quality of Dying and Death Perceived by Family Members and Nurses for Patients Dying in US and Dutch ICUs. AB - BACKGROUND: The Quality of Dying and Death (QODD) questionnaire is used as a self reported measure to allow families and clinicians to assess patients' quality of dying and death. We evaluated end-of-life (EOL) experiences as measured by the QODD completed by families and nurses in the United States and the Netherlands to explore similarities and differences in these experiences and identify opportunities for improving EOL care. METHODS: Questionnaire data were gathered from family members of patients dying in the ICU and nurses caring for these patients. In The Netherlands, data were gathered in three teaching hospitals, and data was gathered from 12 sites participating in a randomized trial in the United States. The QODD consists of 25 items and has been validated in the United States. RESULTS: Data from 446 patients were analyzed (346 in the United States and 100 in the Netherlands). Dutch patients were older than those in the United States (72 + 10.2 years vs 65 + 16.0 years; P < .0025). The family-assessed overall QODD score was the same in both countries: the Netherlands = median, 9; interquartile range (IQR), 8-10 and the United States = median, 8; IQR, 5-10. US family members rated the quality of two items higher than did the Netherlands families: "time spent with loved ones" and "time spent alone." Nurse-assessed QODD ratings varied: the single-item QODD summary score was significantly higher in the Netherlands (the Netherlands: median, 9; IQR, 8-10 vs the United States: median, 7; IQR, 5-8; P < .0025), whereas the QODD total score was higher in the United States (the Netherlands: median, 6.9; IQR, 5.5-7.6 vs the United States: median, 7.1; IQR, 5.8-8.4; P = .014), although it did not meet our criteria for statistical significance. Of the 22 nurse-assessed items, 10 were significantly different between the Netherlands and the United States, with eight having higher scores in the United States and 2 having higher scores in the Netherlands. CONCLUSIONS: The QODD was rated similarly by family members in the United States and the Netherlands but varied when assessed by nurses. These differences may be due to organizational or cultural differences between the two countries or to expectations of respondents. PMID- 27660154 TI - Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease: Retrospective Analysis of 74 Cases. AB - BACKGROUND: Diagnostic evaluation of patients with diffuse parenchymal lung disease (DPLD) is best achieved by a multidisciplinary team correlating clinical, radiological, and pathologic features. Surgical lung biopsy remains the gold standard for histopathologic diagnosis of idiopathic interstitial pneumonias. Emerging data suggest an increasing role for transbronchial cryobiopsy (TBC) in DPLD evaluation. We describe our experience with TBC in patients with DPLD. METHODS: We retrospectively reviewed medical records of patients with radiographic features of DPLD who underwent TBC at Mayo Clinic in Rochester, Minnesota from June 2013 to September 2015. RESULTS: Seventy-four patients (33 women [45%]) with a mean age of 63 years (SD, 13.8) were included. The mean maximal diameter of the samples was 9.2 mm (range, 2-20 mm [SD, 3.9]). The median number of samples per procedure was three (range, one to seven). Diagnostic yield was 51% (38 of 74 specimens). The most frequent histopathologic patterns were granulomatous inflammation (12 patients) and organizing pneumonia (OP) (11 patients), resulting in the final diagnoses of hypersensitivity pneumonitis (six patients), cryptogenic OP (six patients), connective tissue disease-associated OP (three patients), drug toxicity (three patients), infection-related OP (two patients), sarcoidosis (two patients), and aspiration (one patient). Other histopathologic patterns included respiratory bronchiolitis (three patients), acute fibrinous and organizing pneumonia (two patients), desquamative interstitial pneumonia (1 patient), diffuse alveolar damage (one patient), pulmonary alveolar proteinosis (one patient), amyloidosis (one patient), eosinophilic pneumonia (one patient), necrotizing vasculitis (one patient), bronchiolitis with food particles (one patient), and malignancy (three patients). Pneumothorax developed in one patient (1.4%), and bleeding occurred in 16 patients (22%). CONCLUSIONS: Our single-center cohort demonstrated a 51% diagnostic yield from TBC; the rates of pneumothorax and bleeding were 1.4% and 22%, respectively. The optimal use of TBC needs to be determined. PMID- 27660156 TI - Pathological Fracture in Odontoid Process in Multiple Myeloma. PMID- 27660158 TI - A case of acute febrile neck pain. PMID- 27660157 TI - Probiotics Supplemented with Omega-3 Fatty Acids are More Effective for Hepatic Steatosis Reduction in an Animal Model of Obesity. AB - Today probiotics have been suggested as a treatment for the prevention of NAFLD. Omega-3 fatty acid supplementation may have beneficial effects in regulating hepatic lipid metabolism, adipose tissue function and inflammation. The present study was designed to determine whether probiotics plus omega-3 are superior to probiotics alone on the monosodium glutamate (MSG)-induced NAFLD model in rats. We included 60 rats divided into four groups, 15 animals in each. Rats of group I were intact. Newborn rats of groups II-IV were injected with MSG. The III (Symbiter) group received 2.5 ml/kg of multiprobiotic "Symbiter" containing concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter-Omega) groups received "Symbiter-Omega" combination of probiotic biomass supplemented with flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5 %). In both interventional groups reduction in total NAS score was observed. Supplementation of alive probiotic mixture with omega-3 fatty acids lead to 20 % higher decrease in steatosis score (0.73 +/- 0.11 vs 0.93 +/- 0.22, p = 0.848) and reduction by 16.6 % of triglycerides content in liver as compared to probiotic alone. Our study demonstrated more pronounced reduction in hepatic steatosis and hepatic lipid accumulation after treatment with combination of alive probiotics and omega-3 as compared to probiotics alone. PMID- 27660159 TI - A clinical study on single-visit root canal retreatments on consecutive 173 patients: frequency of periapical complications and clinical success rate. AB - OBJECTIVES: This study assessed the outcome measures of single-visit root canal retreatments and frequency of periapical complications considering preoperative, intraoperative and postoperative factors. MATERIALS AND METHODS: Between November 2011 and December 2012, in 173 patients, a total of 234 endodontically treated teeth were retreated in a single appointment by one experienced endodontist. Five teeth were extracted and 119 teeth were lost to follow-up yielding to 110 teeth (47 %) to be examined by two calibrated examiners for the outcome of healing (periapical index score-PAI <=2; no signs or symptoms) or non-healing (presence of apical periodontitis-PAI >2; signs or symptoms). Preoperative, intraoperative and postoperative factors were evaluated for their association with the outcome. Data were analysed using Fisher's exact and Fisher-Freeman Halton tests for bivariate analysis to identify potential outcome predictors. Logistic regression models were used for multivariate analysis to determine significant outcome predictors. RESULTS: Mean observation time was 29 months. Follow-up assessment revealed 100 teeth (90.9 %) as healed and 10 teeth (9.1 %) non-healed. Age, gender, tooth type and preoperative (pain, periodontal defects, root filling density and length), intraoperative (sealer extrusion) and postoperative (type of coronal restorations) factors did not significantly affect the outcome (p > 0.05). Preoperative periradicular lesions with diameters less than 5 mm presented significantly better outcome than larger lesions (p < 0.05; odds ratio (OD) 6; 95 % CI 1.45-24.85). Logistic regression model showed an increased risk of non healing for the parameter of preoperative periradicular lesions with diameters larger than 5 mm (OD 6.42; 95 % CI 1.51-27.27). CONCLUSIONS: Single-appointment root canal retreatments presented a favourable success rate. Only preoperative lesion size had a significant effect on the outcome where the lesions smaller than 5 mm performed significantly better healing. CLINICAL RELEVANCE: Single appointment root canal retreatments could be considered as a viable treatment option for orthograde retreatment cases with periradicular lesion size smaller than 5 mm. PMID- 27660161 TI - Comment on: "The Cost Effectiveness of High-Dose Versus Conventional Haemodialysis: A Systematic Review". PMID- 27660160 TI - Acidogenicity of dual-species biofilms of bifidobacteria and Streptococcus mutans. AB - OBJECTIVE: The aim of this study was to evaluate the acidogenicity of dual species biofilms of bifidobacteria and Streptococcus mutans. MATERIALS AND METHODS: The following strains were tested: Bifidobacterium dentium DSM20436, Parascardovia denticolens DSM10105, and Scardovia inopinata DSM10107. Streptococcus mutans UA159 and Lactobacillus acidophilus ATCC4356 were used as control. Bifidobacteria were studied planktonically as they were not able to form monospecies biofilm, they were grown in biofilms associated with S. mutans. Endogenous polysaccharide reserves of cultures at log phase were depleted. Standardized suspensions of the microorganisms were incubated in growth media supplemented with 10 mM glucose, lactose, raffinose, glucose, or xylitol. S. mutans biofilms were grown on glass cover slips for 24 h to which bifidobacteria were added. After 24 h, the dual-species biofilms were exposed to the same carbon sources, and after 3 h, the pH of spent culture media and concentrations of organic acids were measured. Statistical analyses were carried out using ANOVA and Tukey's test (alpha = 0.05). RESULTS: A higher pH drop was observed when S. mutans was associated with P. denticolens or S. inopinata, in either planktonic or biofilm cultures, than with S. mutans alone. Bifidobacteria showed a higher pH drop in the presence of raffinose than S. mutans or L. acidophilus. CONCLUSIONS: Dual-species biofilms of bifidobacteria and S. mutans produced more acid and greater pH drops than biofilms of S. mutans alone. CLINICAL RELEVANCE: New insights on the complex process of caries pathogenicity contribute to the establishment of preventive and therapeutic measures, in particular in specific cases, such as in early childhood caries. PMID- 27660164 TI - Efficacy of intravitreal aflibercept in Japanese patients with exudative age related macular degeneration. AB - PURPOSE: To clarify the efficacy of aflibercept for treating exudative age related macular degeneration (AMD). METHODS: We prospectively studied 47 eyes with AMD. Forty-seven patients (mean age 72.2 years) received three consecutive monthly intravitreal aflibercept injections followed by an injection every 2 months until 12 months. The primary outcome was the 12-month visual results compared with baseline; the secondary outcomes were the prevalence of geography atrophy (GA), a dry macula at month 12, and anatomic changes on optical coherence tomography. RESULTS: The mean logarithm of the minimum angle of resolution best corrected visual acuity (BCVA) in 27 eyes with typical AMD and 20 eyes with polypoidal choroidal vasculopathy (PCV) significantly (p < 0.0001, p < 0.05, respectively) improved from 0.60 to 0.32 at baseline to 0.29 and 0.21 at month 12. At month 12, 22 (81.5 %) eyes with typical AMD and 17 (85 %) eyes with PCV had dry macula. The subfoveal choroidal thicknesses in typical AMD and PCV decreased significantly (p < 0.0001 for both comparisons) from 241 +/- 118 and 294 +/- 76 MU at baseline to 198 +/- 104 and 244 +/- 84 MU at month 12. Progressing or new GA was seen in three eyes with typical AMD and one eye with PCV; the mean change in the BCVA was significantly (p = 0.0026) worse at month 12. No other complications developed. CONCLUSION: Intravitreal aflibercept significantly improved VA and anatomic changes in typical AMD and PCV over 12 months. Development of GA might be a risk for declining VA. PMID- 27660162 TI - Leukocyte telomere length and ideal cardiovascular health in American Indians: the Strong Heart Family Study. AB - Telomere length, a marker of biological aging, has been associated with cardiovascular disease (CVD) and its risk factors. Ideal cardiovascular health (CVH), defined by the American Heart Association (AHA), has also been associated with a reduced risk of CVD, but the relationship between telomere length and ideal CVH is unclear. We measured leukocyte telomere length (LTL) by qPCR in 2568 American Indians in the Strong Heart Family Study (SHFS). All participants were free of overt CVD at enrollment (2001-2003). CVH indices included four behavioral factors (smoking, physical activity, diet, BMI) and three health factors (blood pressure, cholesterol, fasting glucose). Each index was categorized as poor, intermediate, or ideal according to the AHA's guideline. CVH was further categorized into below average (0-1), average (2-3) and above average (>=4) based on the total number of ideal indices. Results showed that, 29, 50 and 21 % of study participants had below average, average, and above average CVH, respectively. Participants with above average CVH had significantly longer LTL than those with below average CVH (beta = 0.034, P = 0.042) after adjusting for age, sex, education level, marital status, processed meat consumption, alcohol consumption, and study site. Compared to the U.S. general population, American Indians achieved lower rates for five out of the seven ideal CVH metrics, including smoking, BMI, physical activity, diet, and blood pressure. Achieving four or more ideal CVH metrics was significantly associated with longer LTL. This finding suggests that achieving an ideal CVH may prevent or delay CVD, probably through promoting healthy aging. PMID- 27660163 TI - Comparison between ranibizumab and aflibercept for macular edema associated with central retinal vein occlusion. AB - PURPOSE: We compared the efficacy of bimonthly intravitreal injections of ranibizumab (IVR) with that of bimonthly intravitreal injections of aflibercept (IVA) in two prospective, consecutive groups of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). PATIENTS AND METHODS: Eyes with ME after CRVO received either bimonthly IVR (ranibizumab group; n = 13) or IVA (aflibercept group; n = 13) injections and were followed monthly for 6 months. Three patients in the ranibizumab group and two in the aflibercept group were lost to follow-up and excluded from the study. The best-corrected visual acuity (BCVA), central foveal thickness (CFT) on optical coherence tomography, and aqueous vascular endothelial growth factor (VEGF) concentrations were evaluated before and after treatment. RESULTS: From baseline to month 6, significant improvements occurred in mean logMAR BCVA (ranibizumab group: 0.78 0.47; p < 0.05; aflibercept group: 0.74-0.54; p < 0.05) and mean CFT (ranibizumab group: 685-311 um; p < 0.05; aflibercept group: 695-230 um; p < 0.05). Fluctuations in CFT were seen at months 2, 4, and 6 in the ranibizumab group. Mean aqueous VEGF concentration decreased from baseline to month 2 in the ranibizumab group (509.9-348.2 pg/ml) and aflibercept group (412.1 pg/ml to undetectable limits in eight of 11 eyes and to 13.6, 15.6, and 24.1 pg/ml in the other three eyes, respectively). CONCLUSIONS: There was no significant improvement of visual acuity in one group compared with another; VEGF may not be completely neutralized by bimonthly injections of ranibizumab. PMID- 27660166 TI - Ubiquitination-Related MdBT Scaffold Proteins Target a bHLH Transcription Factor for Iron Homeostasis. AB - Iron (Fe) homeostasis is crucial for plant growth and development. A network of basic helix-loop-helix (bHLH) transcription factors positively regulates Fe uptake during iron deficiency. However, their up-regulation or overexpression leads to Fe overload and reactive oxygen species generation, thereby damaging the plants. Here, we found that two BTB/TAZ proteins, MdBT1 and MdBT2, interact with the MbHLH104 protein in apple. In addition, the function of MdBT2 was characterized as a regulator of MdbHLH104 degradation via ubiquitination and the 26S proteasome pathway, thereby controlling the activity of plasma membrane H+ ATPases and the acquisition of iron. Furthermore, MdBT2 interacted with MdCUL3 proteins, which were required for the MdBT2-mediated ubiquitination modification of MdbHLH104 and its degradation. In sum, our findings demonstrate that MdBT proteins interact with MdCUL3 to bridge the formation of the MdBTsMdCUL3 complex, which negatively modulates the degradation of the MdbHLH104 protein in response to changes in Fe status to maintain iron homeostasis in plants. PMID- 27660165 TI - Identification of Homogentisate Dioxygenase as a Target for Vitamin E Biofortification in Oilseeds. AB - Soybean (Glycine max) is a major plant source of protein and oil and produces important secondary metabolites beneficial for human health. As a tool for gene function discovery and improvement of this important crop, a mutant population was generated using fast neutron irradiation. Visual screening of mutagenized seeds identified a mutant line, designated MO12, which produced brown seeds as opposed to the yellow seeds produced by the unmodified Williams 82 parental cultivar. Using forward genetic methods combined with comparative genome hybridization analysis, we were able to establish that deletion of the GmHGO1 gene is the genetic basis of the brown seeded phenotype exhibited by the MO12 mutant line. GmHGO1 encodes a homogentisate dioxygenase (HGO), which catalyzes the committed enzymatic step in homogentisate catabolism. This report describes to our knowledge the first functional characterization of a plant HGO gene, defects of which are linked to the human genetic disease alkaptonuria. We show that reduced homogentisate catabolism in a soybean HGO mutant is an effective strategy for enhancing the production of lipid-soluble antioxidants such as vitamin E, as well as tolerance to herbicides that target pathways associated with homogentisate metabolism. Furthermore, this work demonstrates the utility of fast neutron mutagenesis in identifying novel genes that contribute to soybean agronomic traits. PMID- 27660169 TI - Nonfluorodeoxyglucose-Avid Persistent Splenomegaly at Time of Transplantation Delays Neutrophil and Platelets Engraftment without Affecting Survival in Patients with Lymphomas Undergoing Allogeneic Hematopoietic Cell Transplantation. AB - It is unclear if persistent splenomegaly in the presence of a negative positron emission tomography (PET) scan before allogeneic hematopoietic cell transplantation (HCT) influences post-transplantation outcomes in patients with lymphoma. We retrospectively reviewed records of 152 patients who underwent allogeneic HCT for various lymphomas. Centralized review of pretransplantation computed tomography (CT) and PET images was performed. Spleen volume (SV) was measured using the freehand volume segmentation tool in AW Workstation software (General Electric, Waukesha, WI). Splenic index (SI) was calculated as a product of width, thickness, and length of the spleen. Normal SV was defined as SV < 314.5 cm3 and normal SI was defined as SI <= 480 cm3, as described in the literature. Among the study population, 42.8% received an allogeneic HCT from an HLA-matched related donor, 36.2% from a matched unrelated donor, 12.5% from a mismatched unrelated donor, and 8.6% received a double umbilical cord blood transplantation. Most (61.8%) received myeloablative conditioning. Median age at transplantation was 52 (range, 21 to 68) years. Pre-allogeneic HCT spleen CT and PET images were available on 88% and 70.3% patients, respectively. SV ranged from 90 cm3 to 4684 cm3 with a median of 290.5 cm3 and a mean of 400.3 cm3. SI calculation showed a range from 50.3 cm3 to 8276.4 cm3 with a median of 582.1 cm3 and a mean of 771.2 cm3. The majority of patients (83.1%) had PET-negative spleen before allogeneic transplantation. Engraftment was delayed in PET-negative patients with persistent splenomegaly, with median days to neutrophil engraftment of 17 versus 16 (P = .03) and median days to platelet engraftment of 16 versus 14 (P = .04) when using SV. However, persistent splenomegaly did not appear to impact progression-free survival (P = .11) or overall survival (P = .37). Splenomegaly in the setting of a PET-negative study before allogeneic HCT delays neutrophil and platelet engraftment but does not appear to affect survival. Future studies using registry data or larger multicenter studies would be required to evaluate the impact of splenomegaly and its fluorodeoxyglucose avidity on allogeneic HCT outcomes in specific subtypes of lymphomas. PMID- 27660170 TI - Bone Marrow and Peripheral Blood: Which Is Safe? PMID- 27660167 TI - Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. AB - We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations. We followed the Grading of Recommendations Assessment, Development and Evaluation methodology. For standard-risk CLL we recommend allo-HCT in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. For high-risk CLL an allo-HCT is recommended after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors, regardless of whether an objective response is achieved. For Richter transformation, we recommend allo-HCT upon demonstration of an objective response to anthracycline-based chemotherapy. A reduced-intensity conditioning regimen is recommended whenever indicated. These recommendations highlight the rapidly changing treatment landscape of CLL. Newer therapies have disrupted prior paradigms, and allo-HCT is now relegated to later stages of relapsed or refractory CLL. PMID- 27660172 TI - Comparison of solid and fluid constitutive models of bone marrow during trabecular bone compression. AB - The mechanical environment and mechanobiology of bone marrow may play essential roles in bone adaptation, cancer metastasis, and immune cell regulation. However, the location of marrow within the trabecular pore space complicates experimental measurement of marrow mechanics. Computational models provide a means to assess the shear stress and pressure in the marrow during physiological loading, but they rely on accurate inputs for the marrow and the physics assumed for the interaction of bone and marrow. Elastic, viscoelastic, and fluid constitutive properties have all been reported from experimental measurements of marrow properties. It is unclear whether this ambiguity reflects the various length scales, loading rates, and boundary conditions of the experiments, or if the material models are sufficiently similar as to be interchangeable. To address this question, we analyzed both the mean shear stress and its spatial distribution induced in marrow during compression of trabecular bone cubes when using linear elastic, neo-Hookean, viscoelastic, and power-law fluid constitutive models. Experimentally reported parameters were initially applied for all four constitutive models, resulting in poor agreement. The parameters of the soft solid models were calibrated by linear interpolation so that the volume averaged shear stress agreed with the fluid model for each, but this could only be accomplished on a specimen-by-specimen basis. Following calibration, the root mean-squared (RMS) difference between the solid and fluid constitutive models was still greater than 26% even when the overall mean shear stress was in close agreement, indicating that the spatial distribution of stress is also sensitive to the constitutive model. As such, the choice of constitutive model should be backed by a strong rationale, and results should be interpreted with care. PMID- 27660171 TI - Guidelines for an optimized indentation protocol for measurement of cartilage stiffness: The effects of spatial variation and indentation parameters. AB - Mechanical properties of articular cartilage that are vital to its function are often determined by indentation tests, which can be performed at different scales. Cartilage tissue exhibits various types of structural, geometrical, and spatial variations that pose strict demands on indentation protocols. This study aims to define a reproducible micro-indentation protocol for measuring the effective (average) stiffness of the cartilage surface in a region around 1mm2. We elucidated how different parameters such as indenter size, indenter depth, and the location of the indentation influence the effective elastic modulus measured in micrometer scale on rat knee cartilage. When an indentation was performed (50MUm radial probe, ~10MUm indentation depth) at exactly the same location, the variability was less than 10%, even with a recovery period of 30s. However, there was a high spatial variation and a small change of around 60MUm in location could change the modulus values up to as much as 10-20 fold. The effective elastic modulus of cartilage surface layer cannot therefore be reproducibly determined from a few indentations on a cartilage sample, and requires at least 144 (12*12) indentations for a soft spherical probe with a 50MUm radius. With higher depths, the spatial variation is slightly lower, allowing slightly lower number of indentations (~80 measurements or a 9*9 frame) to provide a representative elastic modulus. Using this protocol, we determined an elastic modulus of 2.6+/ 1.9N/mm2 at the medial side versus a higher modulus of 4.2+/-2.6N/mm2 at the lateral side of the tibia of 12 weeks old Wistar rats. Optimized indentation protocols similar to the one presented here are required for revealing such variations in the mechanical properties of cartilage with anatomical location. PMID- 27660173 TI - Multiple linear regression approach for the analysis of the relationships between joints mobility and regional pressure-based parameters in the normal-arched foot. AB - Plantar load can be considered as a measure of the foot ability to transmit forces at the foot/ground, or foot/footwear interface during ambulatory activities via the lower limb kinematic chain. While morphological and functional measures have been shown to be correlated with plantar load, no exhaustive data are currently available on the possible relationships between range of motion of foot joints and plantar load regional parameters. Joints' kinematics from a validated multi-segmental foot model were recorded together with plantar pressure parameters in 21 normal-arched healthy subjects during three barefoot walking trials. Plantar pressure maps were divided into six anatomically-based regions of interest associated to corresponding foot segments. A stepwise multiple regression analysis was performed to determine the relationships between pressure based parameters, joints range of motion and normalized walking speed (speed/subject height). Sagittal- and frontal-plane joint motion were those most correlated to plantar load. Foot joints' range of motion and normalized walking speed explained between 6% and 43% of the model variance (adjusted R2) for pressure-based parameters. In general, those joints' presenting lower mobility during stance were associated to lower vertical force at forefoot and to larger mean and peak pressure at hindfoot and forefoot. Normalized walking speed was always positively correlated to mean and peak pressure at hindfoot and forefoot. While a large variance in plantar pressure data is still not accounted for by the present models, this study provides statistical corroboration of the close relationship between joint mobility and plantar pressure during stance in the normal healthy foot. PMID- 27660175 TI - The inflammasome in liver disease. PMID- 27660174 TI - Phylogenetic analysis of a transfusion-transmitted hepatitis A outbreak. AB - A transfusion-associated hepatitis A outbreak was found in the first time in Hungary. The outbreak involved five cases. Parenteral transmission of hepatitis A is rare, but may occur during viraemia. Direct sequencing of nested PCR products was performed, and all the examined samples were identical in the VP1/2A region of the hepatitis A virus genome. HAV sequences found in recent years were compared and phylogenetic analysis showed that the strain which caused these cases is the same as that had spread in Hungary recently causing several hepatitis A outbreaks throughout the country. PMID- 27660176 TI - Guillain-Barre Syndrome. PMID- 27660168 TI - National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Patient-Centered Outcomes Working Group Report. AB - In 2015, the National Institutes of Health convened six working groups to address the research needs and best practices for late effects of hematopoietic stem cell transplantation survivors. The Patient-Centered Outcomes Working Group, charged with summarizing the HRQOL evidence base, used a scoping review approach to efficiently survey the large body of literature in adult and pediatric HCT survivors over 1 year after transplantation. The goals of this paper are to (1) summarize the current literature describing patient-centered outcomes in survivors, including the various dimensions of health-related quality of life affected by HCT, and describe interventions tested to improve these outcomes; (2) highlight areas with sufficient evidence allowing for integration into standard practice; (3) address methodological issues that restrict progress in this field; (4) identify major gaps to guide future research; and (5) specify priority research recommendations. Patient-centered outcomes were summarized within physical, psychological, social, and environmental domains, as well as for adherence to treatment, and health behaviors. Interventions to improve outcomes were evaluated for evidence of efficacy, although few interventions have been tested in long-term HCT survivors. Methodologic issues defined included lack of consistency in the selection of patient-centered outcome measures, along with the absence of a standard for timing, frequency, and mode of administration. Recommendations for HCT survivorship care included integration of annual screening of patient-centered outcomes, use of evidence-based practice guidelines, and provision of treatment summaries and survivorship care plans after HCT. Three priority research recommendations included the following: (1) design and test risk-targeted interventions with dose-intensity modulation matching the needs of HCT survivors with priority domains, including sexual dysfunction, fatigue, sleep disruption, nonadherence to medications and recommended health care, health behaviors including physical inactivity and healthy eating, and psychological dysfunction, with particular consideration of novel technologies to reach HCT survivors distant from their transplantation centers; (2) design a consensus-based methodologic framework for outcomes evaluation; and (3) evaluate and compare existing practices for integrating patient-centered outcome screening and interventions across HCT survivorship programs. PMID- 27660177 TI - Subarachnoid Hemorrhage and Spinal Subdural Hematoma Due to Acute CSF Hypotension. AB - BACKGROUND: Intracranial subarachnoid hemorrhage (SAH) and spinal subdural hematoma (SDH) are rare complications of spine surgery, thought to be precipitated by cerebrospinal fluid (CSF) hypotension in the setting of an intraoperative durotomy or postoperative CSF leak. Considerable clinical variability has been reported, requiring a high level of clinical suspicion in patients with a new, unexplained neurologic deficit after spine surgery. METHODS: Case report. RESULTS: An 84-year-old man developed symptomatic spinal stenosis with bilateral lower extremity pseudoclaudication. He underwent L3-5 laminectomy at an outside institution, complicated by a small, incidental, unrepairable intraoperative durotomy. On postoperative day 2, he became confused; and head CT demonstrated intracranial SAH with blood products along the superior cerebellum and bilateral posterior Sylvian fissures. He was transferred to our neurosciences ICU for routine SAH care, with improvement in encephalopathy over several days of supportive care. On postoperative day 10, the patient developed new bilateral lower extremity weakness; MRI of the lumbar spine demonstrated worsening acute spinal SDH above the laminectomy defect, from L4-T12. He was taken to the OR for decompression, at which time a complex 1.5-cm lumbar durotomy was identified and repaired primarily. CONCLUSIONS: We report the first case of simultaneous intracranial SAH and spinal SDH attributable to postoperative CSF hypotension in the setting of a known intraoperative durotomy. Although rare, each of these entities has the potential to precipitate a poor neurologic outcome, which may be mitigated by early recognition and treatment. PMID- 27660178 TI - Development of a Comprehensive Assessment of Food Parenting Practices: The Home Self-Administered Tool for Environmental Assessment of Activity and Diet Family Food Practices Survey. AB - BACKGROUND: Parents' food parenting practices influence children's dietary intake and risk for obesity and chronic disease. Understanding the influence and interactions between parents' practices and children's behavior is limited by a lack of development and psychometric testing and/or limited scope of current measures. The Home Self-Administered Tool for Environmental Assessment of Activity and Diet (HomeSTEAD) was created to address this gap. OBJECTIVE: This article describes development and psychometric testing of the HomeSTEAD family food practices survey. PARTICIPANTS/DESIGN: Between August 2010 and May 2011, a convenience sample of 129 parents of children aged 3 to 12 years were recruited from central North Carolina and completed the self-administered HomeSTEAD survey on three occasions during a 12- to 18-day window. Demographic characteristics and child diet were assessed at Time 1. Child height and weight were measured during the in-home observations (following Time 1 survey). STATISTICAL ANALYSIS: Exploratory factor analysis with Time 1 data was used to identify potential scales. Scales with more than three items were examined for scale reduction. Following this, mean scores were calculated at each time point. Construct validity was assessed by examining Spearman rank correlations between mean scores (Time 1) and children's diet (fruits and vegetables, sugar-sweetened beverages, snacks, sweets) and body mass index (BMI) z scores. Repeated measures analysis of variance was used to examine differences in mean scores between time points, and single-measure intraclass correlations were calculated to examine test-retest reliability between time points. RESULTS: Exploratory factor analysis identified 24 factors and retained 124 items; however, scale reduction narrowed items to 86. The final instrument captures five coercive control practices (16 items), seven autonomy support practices (24 items), and 12 structure practices (46 items). All scales demonstrated good internal reliability (alpha>.62), 18 factors demonstrated construct validity (significant association with child diet, P<0.05), and 22 demonstrated good reliability (intraclass correlation coefficient>0.61). CONCLUSIONS: The HomeSTEAD family food practices survey provides a brief, yet comprehensive and psychometrically sound assessment of food parenting practices. PMID- 27660180 TI - Medicinal herbs as a potential strategy to decrease methane production by rumen microbiota: a systematic evaluation with a focus on Perilla frutescens seed extract. AB - Mitigation of the methane (CH4) emission from ruminants is needed to decrease the environmental impact of ruminant animal production. Different plant materials and chemicals have been tested, but few are both effective and practical. Medicinal herbs contain biological compounds and antimicrobials that may be effective in lowering the CH4 production. However, few studies have systematically evaluated medicinal herbs for their effect on CH4 production or on the rumen microbiota. In this study, extracts from 100 medicinal herbs were assessed for their ability to decrease CH4 production by rumen microbiota in vitro. The extracts of 12 herbs effectively lowered the CH4 production, with the extract of Perilla frutescens seeds being the most effective. The major components of P. frutescens seed extract were identified, and the effects of the extract on the fermentation characteristics and populations of rumen methanogens, fungi, protozoa, and select bacteria were also assessed. The decreased CH4 production induced by the P. frutescens seed extract was accompanied by an increased abundance of Ruminobacter, Selenomonas, Succinivibrio, Shuttleworthis, Pseudobutyrivbrio, Anaerovibrio, and Roseomonas and a decreased abundance of Methanobrevibacter millerae. The abundance of Pedobacter, Anaeroplasma, Paludibacter, Ruminococcus, and unclassified Lachnospiraceae was positively correlated with the CH4 production, with no effects on volatile fatty acids. This study suggests that medicinal herbs may be used to mitigate the CH4 emission from ruminants. PMID- 27660179 TI - Expression of prophage-encoded endolysins contributes to autolysis of Lactococcus lactis. AB - Analysis of autolysis of derivatives of Lactococcus lactis subsp. cremoris MG1363 and subsp. lactis IL1403, both lacking the major autolysin AcmA, showed that L. lactis IL1403 still lysed during growth while L. lactis MG1363 did not. Zymographic analysis revealed that a peptidoglycan hydrolase activity of around 30 kDa is present in cell extracts of L. lactis IL1403 that could not be detected in strain MG1363. A comparison of all genes encoding putative peptidoglycan hydrolases of IL1403 and MG1363 led to the assumption that one or more of the 99 % homologous 27.9-kDa endolysins encoded by the prophages bIL285, bIL286 and bIL309 could account for the autolysis phenotype of IL1403. Induced expression of the endolysins from bIL285, bIL286 or bIL309 in L. lactis MG1363 resulted in detectable lysis or lytic activity. Prophage deletion and insertion derivatives of L. lactis IL1403 had a reduced cell lysis phenotype. RT-qPCR and zymogram analysis showed that each of these strains still expressed one or more of the three phage lysins. A homologous gene and an endolysin activity were also identified in the natural starter culture L. lactis subsp. cremoris strains E8, Wg2 and HP, and the lytic activity could be detected under growth conditions that were identical as those used for IL1403. The results presented here show that these endolysins of L. lactis are expressed during normal growth and contribute to autolysis without production of (lytic) phages. Screening for natural strains expressing homologous endolysins could help in the selection of strains with enhanced autolysis and, thus, cheese ripening properties. PMID- 27660181 TI - Identification and characterization of a common B-cell epitope on EIAV capsid proteins. AB - The equine infectious anemia virus (EIAV) capsid protein (p26) is one of the major immunogenic proteins during EIAV infection and is widely used for the detection of EIAV antibodies in horses. However, few reports have described the use of EIAV-specific monoclonal antibodies (MAbs) in etiological and immunological detection. Previously, we developed an antigen capture enzyme linked immunosorbent assay (AC-ELISA) for the quantification of the EIAV p26 protein level. However, the epitopes recognized by the MAbs were not identified, and the utilization of the MAbs needs to be evaluated. In this study, we characterized two monoclonal antibodies (9H8 and 1G11 MAbs) against EIAV p26. Two B-cell epitopes are located in amino acid residues, 73NLDKIAEE81 (HE) and 199KNAMRHLRPEDTLEEKMYAC218 (GE) for the 9H8 and 1G11 MAbs, respectively. The 1G11 epitope (GE) varied among viruses isolated worldwide but can be recognized by anti-EIAV sera from different regions, including China, the USA, and Argentina. Meanwhile, 1G11 MAb could react with the mutants of almost all the EIAV strains. Furthermore, we found that the histidine at position 204 (H204), leucine at position 205 (L205), and aspartic acid at position 209 (D209) of EIAV p26 individually played pivotal roles in binding with the 1G11 MAb. Our results revealed that the GE peptide might be a common B-cell binding epitope of EIAV antibodies. This is also the first report to identify a broad-spectrum monoclonal antibody (1G11) against p26 of EIAV. These findings may provide a useful basis for the development of new diagnostic assays for EIAV. PMID- 27660183 TI - ? PMID- 27660182 TI - Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells. AB - Previously, it has been reported that molecules built on the benzanilide and thiobenzanilide scaffold are the promising groups of compounds with several biological activities including antifungal, antimycotic, antibacterial, spasmolytic, and anticancer ones. In this study the mechanism of action of one selected thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5 trifluorobenzothioamide (63T) with strongest cytotoxic activity has been investigated for the first time in human lung adenocarcinoma (A549) and normal lung derived fibroblast (CCD39Lu) in a cell culture model. The results demonstrated, that 63T can be considered a selective anticancer compound. Based on these results, several experiments including the analysis of cellular morphology, cell phase distribution, cytoplasmic histone-associated DNA fragmentation, apoptosis, necrosis, and autophagy detection were performed to understand better the mechanism underlying the anticancer activity. The data showed that 63T is a small molecule compound, which selectively induces cancer cell death in a caspase independent pathway; moreover, the autophagic dose dependent processes may be involved in the mechanism of cell death. PMID- 27660184 TI - Reasoning about truth-telling in end-of-life care of patients with acute stroke. AB - BACKGROUND: Ethical problems are a universal phenomenon but rarely researched concerning patients dying from acute stroke. These patients often have a reduced consciousness from stroke onset and thereby lack ability to convey their needs and could be described as 'incompetent' decision makers regarding their own care. OBJECTIVE: The aim of the study was to deepen the understanding of stroke team members' reasoning about truth-telling in end-of-life care due to acute stroke. RESEARCH DESIGN: Qualitative study based on individual interviews utilizing combined deductive and inductive content analysis. Participants and research context: A total of 15 stroke team members working in stroke units of two associated county hospitals in western Sweden participated. Ethical considerations: The study was approved by the Regional Ethics Review Board, Gothenburg, Sweden. FINDINGS: The main findings were the team members' dynamic movement between the categories 'Truth above all' and 'Hide truth to protect'. Honesty was highly valued and considered as a reason for always telling the truth, with the argument of truth as common morality. However, the carers also argued for hiding the truth for different reasons such as not adding extra burden in the sorrow, awaiting a timely moment and not being a messenger of bad news. Withholding truth could both be seen as a way of protecting themselves from difficult conversations and to protect others. DISCUSSION: The results indicate that there are various barriers for truthfulness. Interpreted from a virtue of ethics perspective, withholding of truth might also be seen as an expression of sound judgement to put the patient's best interest first. CONCLUSION: The carers may need support in the form of supervision to be given space to reflect on their experience and thereby promote ethically justified care. Here, the multi professional team can be of great value and contribute through inter-professional sharing of knowledge. PMID- 27660185 TI - Moral distress in critical care nursing: The state of the science. AB - BACKGROUND: Moral distress is a complex phenomenon frequently experienced by critical care nurses. Ethical conflicts in this practice area are related to technological advancement, high intensity work environments, and end-of-life decisions. OBJECTIVES: An exploration of contemporary moral distress literature was undertaken to determine measurement, contributing factors, impact, and interventions. REVIEW METHODS: This state of the science review focused on moral distress research in critical care nursing from 2009 to 2015, and included 12 qualitative, 24 quantitative, and 6 mixed methods studies. RESULTS: Synthesis of the scientific literature revealed inconsistencies in measurement, conflicting findings of moral distress and nurse demographics, problems with the professional practice environment, difficulties with communication during end-of-life decisions, compromised nursing care as a consequence of moral distress, and few effective interventions. CONCLUSION: Providing compassionate care is a professional nursing value and an inability to meet this goal due to moral distress may have devastating effects on care quality. Further study of patient and family outcomes related to nurse moral distress is recommended. PMID- 27660186 TI - Letter by Counago et al. regarding article "Impact of multiparametric magnetic resonance imaging on risk group assessment of patients with prostate cancer addressed to external beam radiation therapy". PMID- 27660188 TI - Transport of Organic Compounds Through Porous Systems Containing Humic Acids. AB - Soil pollution by the presence of different contaminants (e.g. heavy metal ions or pesticides) is one of the biggest problems worldwide. The positive affinity of natural humic acids towards these contaminants might contribute to the soil and ground water protection; therefore it is necessary to study the reactivity and barrier properties of humic acids. An original reactivity-mapping tool based on diffusion techniques designed to study the reactivity and barrier properties of polyelectrolytes was developed and tested on humic acids. The results of diffusion experiments demonstrate that the electrostatic interactions between humic acids functioning as a polyelectrolyte interpenetrated in a supporting hydrogel matrix (agarose) and cationic dye (methylene blue) as a model solute have a crucial impact on the rate of diffusion processes and on the barrier properties of hydrogels. The intensity of interactions was evaluated by fundamental diffusion parameters (effective diffusion coefficients and breakthrough time). The impact of modification of humic acids was also studied by means of diffusion experiments conducted on two types of standard humic acids (Leonardite 1S104H) and humic acids with selectively methylated carboxylic groups. PMID- 27660187 TI - Microstructural strength deterioration of aerobic granule sludge under organic loading swap. AB - This study revealed that the gross indicators commonly adopted for monitoring the performance of aerobic granular sludge processes are not capable of probing the microstructural deterioration of granule interior upon organic loading swaps. These granules subjected to loading swaps retained their global characteristics: appearances, sizes and settling velocities, chemical oxygen demand (COD) and ammonia-nitrogen removal capacities. However, the granule interior strength, as determined by ultrasound method, was largely weakened upon COD switch-off and was not recovered in the subsequent COD re-supply stage. In response to COD switch off, the 5.6kDa polysaccharides component of granule extracellular polymeric substances (EPS) was diminished. Correspondingly, two bacterial species, Thauera and Sphingomonas sp., were faded away together with the significant decline in contents of intracellular cyclic dimeric GMP (c-di-GMP). The microstructural integrity of granules was seriously deteriorated upon COD switch-off, which was not detectable by the commonly adopted gross indicators. PMID- 27660189 TI - Comparison of Three Analytical Methods for the Quantitation of Mercury in Environmental Samples from the Volta Lake, Ghana. AB - Three analytical methods using automatic mercury analyzer (AMA), direct mercury analyzer (DMA) and inductively coupled plasma-mass spectrometry (ICP-MS) were applied to determine mercury in fish and sediment samples from the Volta Lake in Ghana with the aim of comparing their accuracy, precision, and limit of quantifications. There was statistically no significant difference (p < 0.05) between the concentrations recorded by the methods. This indicates their suitability for the accurate determination of mercury. Limit of quantification was found to be in the order; ICP-MS (0.053 ng/g) < DMA (0.527 ng/g) < AMA (2.193 ng/g). Though each of the three methods has a suitable ability in determining accurately the concentrations of mercury in fish and sediment, for the determination of very low concentrations of mercury ICP-MS should be preferred considering the order of the detection limit which follows the trend ICP-MS (0.016 ng/g) < DMA (0.158 ng/g) < AMA (0.509 ng/g). PMID- 27660190 TI - Glycemic Control Indices and Their Aggregation in the Prediction of Nocturnal Hypoglycemia From Intermittent Blood Glucose Measurements. AB - BACKGROUND: Despite the risk associated with nocturnal hypoglycemia (NH) there are only a few methods aiming at the prediction of such events based on intermittent blood glucose monitoring data. One of the first methods that potentially can be used for NH prediction is based on the low blood glucose index (LBGI) and suggested, for example, in Accu-Chek(r) Connect as a hypoglycemia risk indicator. On the other hand, nowadays there are other glucose control indices (GCI), which could be used for NH prediction in the same spirit as LBGI. In the present study we propose a general approach of combining NH predictors constructed from different GCI. METHODS: The approach is based on a recently developed strategy for aggregating ranking algorithms in machine learning. NH predictors have been calibrated and tested on data extracted from clinical trials, performed in EU FP7-funded project DIAdvisor. Then, to show a portability of the method we have tested it on another dataset that was received from EU Horizon 2020-funded project AMMODIT. RESULTS: We exemplify the proposed approach by aggregating NH predictors that have been constructed based on 4 GCI associated with hypoglycemia. Even though these predictors have been preliminary optimized to exhibit better performance on the considered dataset, our aggregation approach allows a further performance improvement. On the dataset, where a portability of the proposed approach has been demonstrated, the aggregating predictor has exhibited the following performance: sensitivity 77%, specificity 83.4%, positive predictive value 80.2%, negative predictive value 80.6%, which is higher than conventionally considered as acceptable. CONCLUSION: The proposed approach shows potential to be used in telemedicine systems for NH prediction. PMID- 27660191 TI - Bevacizumab in colorectal cancer: it should have worked. PMID- 27660192 TI - Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial. AB - BACKGROUND: Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. METHODS: For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7.5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. FINDINGS: Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4.92 years (IQR 4.00 5.16). Disease-free survival at 3 years did not differ between the groups (75.4%, 95% CI 72.5-78.0 in the capecitabine and bevacizumab group vs 78.4%, 75.7-80.9 in the capecitabine alone group; hazard ratio 1.06, 95% CI 0.89-1.25, p=0.54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of 959 in the capecitabine and bevacizumab group) and diarrhoea (102 [11%] vs 104 [11%]), and, with the addition of bevacizumab, expected increases were recorded in all-grade hypertension (320 [33%] vs 75 [8%]), proteinuria (197 [21%] vs 49 [5%]), and wound healing problems (30 [3%] vs 17 [2%]). 571 serious adverse events were reported (221 with capecitabine alone and 350 with capecitabine and bevacizumab). Most of these were gastrointestinal (n=245) or cardiovascular (n=169). 23 deaths within 6 months of randomisation were classified as being related to treatment, eight in the capecitabine alone group and 15 in the capecitabine and bevacizumab group. INTERPRETATION: The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used. FUNDING: Roche. PMID- 27660193 TI - Role of individual disulfide bridges in the conformation and activity of spinoxin (alpha-KTx6.13), a potassium channel toxin from Heterometrus spinifer scorpion venom. AB - Spinoxin (SPX; alpha-KTx6.13), isolated from venom of the scorpion Heterometrus spinifer, is a K+ channel-specific peptide toxin (KTx), which adopts a cysteine stabilized alpha/beta scaffold that is cross-linked by four disulfide bridges (Cys1-Cys5, Cys2-Cys6, Cys3-Cys7, and Cys4-Cys8). To investigate the role of the individual disulfide bonds in the structure-activity relationship of SPX, we synthesized four SPX analogs in which each pair of cysteine residues was replaced by alanine residues. The analysis of circular dichroism spectra and inhibitory activity against Kv1.3 channels showed that the SPX analogs lacking any of three specific disulfide bonds (Cys1-Cys5, Cys2-Cys6, and Cys3-Cys7) were unable to form the native secondary structure and completely lost inhibitory activities. Thus, we conclude that Cys1-Cys5, Cys2-Cys6, and Cys3-Cys7 are required for the inhibition of the Kv1.3 channel by SPX. In contrast, the analog lacking Cys4-Cys8 retained both native secondary structure and inhibitory activity. Interestingly, one of the isomers of the analog lacking Cys1-Cys5 also showed inhibitory activities, although its inhibition was ~18-fold weaker than native SPX. This isomer had an atypical disulfide bond pairing (Cys3-Cys4 and Cys7-Cys8) that corresponds to that of maurotoxin (MTX), another alpha-KTx6 family member. These results indicate that the Cys1-Cys5 and Cys2-Cys6 bonds are important for restricting the toxin from forming an atypical (MTX-type) disulfide bond pairing among the remaining four cysteine residues (Cys3, Cys4, Cys7, and Cys8) in native SPX. PMID- 27660194 TI - Physical Exercise for Late-Life Depression: Effects on Heart Rate Variability. AB - OBJECTIVES: Late-life major depression is associated with increased cardiovascular risk and impaired autonomic control of the heart, as evident from reduced heart rate variability (HRV). Moreover, antidepressant drug therapy also might be associated with further reductions of HRV. In the SEEDS study, we investigated whether sertraline associated with physical exercise protocols led to improvements of HRV, compared with antidepressant drug therapy alone. DESIGN: Single-blind randomized controlled trial. SETTING: Psychiatric consultation liaison program for primary care. PARTICIPANTS: Patients aged 65-85 years with major depression, recruited from primary care. INTERVENTIONS: Sertraline plus structured, tailored group physical exercise (S + EX) versus sertraline alone (S) for 24 weeks. MEASUREMENTS: HRV indices (RR, percentage of NN intervals greater than 50 msec [pNN50], square root of the mean squared differences of successive NN intervals [RMSSD], standard deviation of heart rate [SDHR], standard deviation of the NN interval [SDNN], high-frequency band [HF], low-frequency band [LF], and their ratio [LF/HF]) were measured at baseline, week 12, and week 24. Psychiatric and medical assessments. RESULTS: Participants displayed significant improvements of most HRV indices over time, irrespective of the group assignment (pNN50, RMSSD, SDHR, SDNN, HF, LF, and LF/HF). Moreover, patients in the S + EX group displayed greater increases of different HRV indices(RR, pNN50, RMSSD, SDHR, SDNN, HF, and LF) compared with those in the S group. CONCLUSIONS: The combination of structured physical exercise and sertraline might exert positive effects on the autonomic control of the heart among older patients with major depression. PMID- 27660196 TI - UK performs fifth in the world on sustainable development goals. PMID- 27660195 TI - Behavioral Interventions for Patients with Major Depression and Severe COPD. PMID- 27660197 TI - Presence and distribution of leptin and leptin receptor in the canine gallbladder. AB - The hormone leptin is produced by mature adipocytes and plays an important role in regulating food intake and energy metabolism through its interaction with the leptin receptor. In addition to roles in obesity and obesity-related diseases, leptin has been reported to affect the components and secretion of bile in leptin deficient mice. Furthermore, gallbladder diseases such as cholelithiasis are known to be associated with serum leptin concentrations in humans. We hypothesized that the canine gallbladder is a source of leptin and that the leptin receptor may be localized in the gallbladder, where it plays a role in regulating the function of this organ. The aim of this study was to demonstrate the presence and expression patterns of leptin and its receptors in normal canine gallbladders using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry. Clinically normal gallbladder tissue samples were obtained from four healthy beagle dogs with similar body condition scores. RT-PCR and sequencing of the amplified PCR products revealed the presence of leptin mRNA and its receptors in the gallbladder. Immunohistochemical investigations demonstrated the expression of leptin and its receptors in the luminal single columnar and tubuloalveolar glandular epithelial cells. In conclusion, the results of this study demonstrated the presence of leptin and its receptors in the gallbladders of dogs. Leptin and its receptor were both localized throughout the cytoplasm of luminal and glandular epithelial cells. These results suggested that the gallbladder is not only a source of leptin, but also a target of leptin though autocrine/paracrine mechanisms. The results of this study could increase the understanding of both the normal physiological functions of the gallbladder and the pathophysiological mechanisms of gallbladder diseases characterized by leptin system dysfunction. PMID- 27660198 TI - PD-1/PD-L and autoimmunity: A growing relationship. AB - Programmed death 1 (PD-1) and its ligands, namely PD-L1 and PD-L2, are one of the key factors responsible for inhibitory T cell signaling, mediating the mechanisms of tolerance and providing immune homeostasis. Mounting evidence demonstrates that impaired PD-1:PD-L function plays an important role in a variety of autoimmune diseases such as Type 1 diabetes (T1D), encephalomyelitis, inflammatory bowel diseases (IBD), Rheumatoid Arthritis (RA), autoimmune hepatitis (AIH), Behcet's disease (BD), myasthenia gravis (MG), autoimmune uveitis (AU), Sjogren's syndrome (SjS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myocarditis, and ankylosing spondylitis (AS). By investigating the candidate genes, genome-wide association studies, and identification of single nucleotide polymorphisms (SNPs) in PD-1 gene in humans, it has been shown that there is a higher risk in relevant genetic associations with developing autoimmune diseases in certain ethnic groups. In this review we have tried to present a comprehensive role of PD-1:PD-L in all recently studied autoimmune diseases. PMID- 27660199 TI - Diet quality as measured by the Diet Quality Index-International is associated with prospective changes in body fat among Canadian children. AB - OBJECTIVE: To quantify the association of dietary quality with prospective changes in adiposity. DESIGN: Children participating in the QUALITY (QUebec Adipose and Lifestyle InvesTigation in Youth) study underwent examination at baseline and at 2-year follow-up. Dietary quality was assessed by the Diet Quality Index-International (DQII) using three non-consecutive 24 h diet recalls at baseline. The DQII has four main categories: dietary adequacy, variety, moderation and overall balance. Fat mass index (FMI; [fat mass (kg)]/[height (m)]2), central FMI (CFMI; [trunk fat mass (kg)]/[height (m)]2), percentage body fat (%BF; [total fat mass (kg)]/[total mass (kg)]) and percentage central BF (%CBF; [trunk fat mass (kg)]/[total mass (kg)]) were assessed through dual-energy X-ray absorptiometry. SETTING: Children were selected from schools in the greater Montreal, Sherbrooke and Quebec City metropolitan areas between 2005 and 2008, Quebec, Canada. SUBJECTS: A total of 546 children aged 8-10 years, including 244 girls and 302 boys. RESULTS: Regression analysis adjusting for age, sex, energy intake, physical activity and Tanner stage revealed that every 10-unit improvement in overall DQII score was associated with lower gain in CFMI (beta= 0.08; 95 % CI -0.17, -0.003) and %BF (beta=-0.55; 95 % CI -1.08, -0.02). Each unit improvement in dietary adequacy score was associated with lower gain in FMI (beta=-0.05; 95 % CI -0.08, -0.008), CFMI (beta=-0.03; 95 % CI -0.05, -0.007), %BF (beta=-0.15; 95 % CI -0.28, -0.03) and %CBF (beta=-0.09; 95 % CI -0.15, 0.02). CONCLUSIONS: Promotion of dietary quality and adequacy may reduce weight gain in childhood and prevent chronic diseases later in life. PMID- 27660201 TI - Time-of-day-dependent adaptation of the HPA axis to predictable social defeat stress. AB - In modern societies, the risk of developing a whole array of affective and somatic disorders is associated with the prevalence of frequent psychosocial stress. Therefore, a better understanding of adaptive stress responses and their underlying molecular mechanisms is of high clinical interest. In response to an acute stressor, each organism can either show passive freezing or active fight-or flight behaviour, with activation of sympathetic nervous system and the hypothalamus-pituitary-adrenal (HPA) axis providing the necessary energy for the latter by releasing catecholamines and glucocorticoids (GC). Recent data suggest that stress responses are also regulated by the endogenous circadian clock. In consequence, the timing of stress may critically affect adaptive responses to and/or pathological effects of repetitive stressor exposure. In this article, we characterize the impact of predictable social defeat stress during daytime versus nighttime on bodyweight development and HPA axis activity in mice. While 19 days of social daytime stress led to a transient reduction in bodyweight without altering HPA axis activity at the predicted time of stressor exposure, more detrimental effects were seen in anticipation of nighttime stress. Repeated nighttime stressor exposure led to alterations in food metabolization and reduced HPA axis activity with lower circulating adrenocorticotropic hormone (ACTH) and GC concentrations at the time of predicted stressor exposure. Our data reveal a circadian gating of stress adaptation to predictable social defeat stress at the level of the HPA axis with impact on metabolic homeostasis underpinning the importance of timing for the body's adaptability to repetitive stress. PMID- 27660202 TI - Contact rates of wild-living and domestic dog populations in Australia: a new approach. AB - Dogs (Canis familiaris) can transmit pathogens to other domestic animals, humans and wildlife. Both domestic and wild-living dogs are ubiquitous within mainland Australian landscapes, but their interactions are mostly unquantified. Consequently, the probability of pathogen transfer among wild-living and domestic dogs is unknown. To address this knowledge deficit, we established 65 camera trap stations, deployed for 26,151 camera trap nights, to quantify domestic and wild living dog activity during 2 years across eight sites in north-east New South Wales, Australia. Wild-living dogs were detected on camera traps at all sites, and domestic dogs recorded at all but one. No contacts between domestic and wild living dogs were recorded, and limited temporal overlap in activity was observed (32 %); domestic dogs were predominantly active during the day and wild-living dogs mainly during the night. Contact rates between wild-living and between domestic dogs, respectively, varied between sites and over time (range 0.003-0.56 contacts per camera trap night). Contact among wild-living dogs occurred mainly within social groupings, and peaked when young were present. However, pup emergence occurred throughout the year within and between sites and consequently, no overall annual cycle in contact rates could be established. Due to infrequent interactions between domestic and wild-living dogs, there are likely limited opportunities for pathogen transmission that require direct contact. In contrast, extensive spatial overlap of wild and domestic dogs could facilitate the spread of pathogens that do not require direct contact, some of which may be important zoonoses. PMID- 27660200 TI - An in vitro model of murine middle ear epithelium. AB - Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air-liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host-pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development. PMID- 27660203 TI - Delayed threshold response of a rodent population to human-induced landscape change. AB - Theory predicts that due to their resilience, ecosystems and populations are expected to respond to environmental changes not gradually, but in a nonlinear way with sudden abrupt shifts. However, it is not easy to observe and predict the state-and-transition dynamics in the real world because of time lags between exogenous perturbations and species response. Based on yearly surveys, during 21 years (1994-2014), we have studied population dynamics of a desert rodent (the midday gerbil, Meriones meridianus) in the rangelands of southern Russia under landscape change from desert to steppe caused by the drastic reduction of livestock after the collapse of the USSR in the early 1990s. The population of M. meridianus has remained robust to landscape change from desert to steppe for over 10 years, but then has suddenly dropped down and has not recovered since. The step transition from the high- to low-abundance density-regulated equilibrium was accompanied by an abrupt increase in the spatio-temporal population variability, which may indicate the loss of population resilience. We explain inertia in species response to landscape change and an abrupt regime shift in population dynamics by species-specific ecology and life-history combined with habitat fragmentation that had reached a certain critical threshold level by the early 2000s. This is a rare well-documented demonstration of a delayed threshold response of a wild unexploited mammal population to human-induced environmental change, which may shed light on the mechanisms of population resilience and underlying causes of threshold population dynamics in a changing world. PMID- 27660205 TI - The Lack of Mutagenic Potential of a Guanine-Rich Triplex Forming Oligonucleotide in Physiological Conditions. AB - Triplex forming oligonucleotides (TFOs) bind in the major groove of DNA duplex in a sequence-specific manner imparted by Hoogsteen hydrogen bonds. There have been several reports demonstrating the ability of guanine-rich TFOs to induce targeted mutagenesis on an exogenous plasmid or an endogenous chromosomal locus. In particular, a 30mer guanine-rich triplex forming oligonucleotide, AG30, optimally designed to target the supFG1 reporter gene was reported to be mutagenic in the absence of DNA reactive agents in cultured cells and in vivo Here, we investigated the mutagenic potential of AG30 using the supFG1 shuttle vector forward mutation assay under physiological conditions. We also assessed the triplex binding potential of AG30 alongside cytotoxic and mutagenic assessment. In a cell free condition, AG30 was able to bind its polypurine target site in the supFG1 gene in the absence of potassium chloride and also aligned with a 5-fold increase in the mutant frequency when AG30 was pre-incubated with the supFG1 plasmid in the absence of potassium prior to transfection into COS-7 cells. However, when we analyzed triplex formation of AG30 and the supFG1 target duplex at physiological potassium levels, triplex formation was inhibited due to the formation of competing secondary structures. Subsequent assessment of mutant frequency under physiological conditions, by pre-transfecting COS-7 cells with the supFG1 plasmid prior to AG30 treatment led to a very small increase (1.4 fold) in the mutant frequency. Transfection of cells with even higher concentrations of AG30 did result in an elevated mutagenic response but this was also seen with a scrambled sequence, and was therefore considered unlikely to be biologically relevant as an associated increase in cytotoxicity was also apparent. Our findings also provide further assurance on the low potential of triplex-mediated mutation as a consequence of unintentional genomic DNA binding by therapeutic antisense oligonucleotides. PMID- 27660204 TI - MC1568 Inhibits Thimerosal-Induced Apoptotic Cell Death by Preventing HDAC4 Up Regulation in Neuronal Cells and in Rat Prefrontal Cortex. AB - Ethylmercury thiosalicylate (thimerosal) is an organic mercury-based compound commonly used as an antimicrobial preservative that has been found to be neurotoxic. In contrast, histone deacetylases (HDACs) inhibition has been found to be neuroprotective against several environmental contaminants, such as polychlorinated biphenyls, di-2-ethylhexyl phthalate, and methylmercury. The aim of this study was to investigate the effect of HDAC inhibition on thimerosal induced neurotoxicity in neuroblastoma cells and cortical neurons. Interestingly, we found that thimerosal, at 0.5 MUM in SH-SY5Y cells and at 1 MUM in neurons, caused cell death by activation of apoptosis, which was prevented by the HDAC class IIA inhibitor MC1568 but not the class I inhibitor MS275. Furthermore, thimerosal specifically increased HDAC4 protein expression but not that of HDACs 5, 6, 7, and 9. Western blot analysis revealed that MC1568 prevented thimerosal induced HDAC4 increase. In addition, both HDAC4 knocking-down and MC1568 inhibited thimerosal-induced cell death in SH-SY5Y cells and cortical neurons. Importantly, intramuscular injection of 12 MUg/kg thimerosal on postnatal days 7, 9, 11, and 15 increased HDAC4 levels in the prefrontal cortex (PFC), which decreased histone H4 acetylation in infant male rats, in parallel increased motor activity changes. In addition, coadministration of 40 mg/kg MC1568 (intraperitoneal injection) moderated the HDAC4 increase which reduced histone H4 deacetylation and caspase-3 cleavage in the PFC. Finally, open-field testing showed that thimerosal-induced motor activity changes are reduced by MC1568. These findings indicate that HDAC4 regulates thimerosal-induced cell death in neurons and that treatment with MC1568 prevents thimerosal-induced activation of caspase-3 in the rat PFC. PMID- 27660206 TI - Intrahepatic biliary duct branching patterns, cystic duct anomalies, and pancreas divisum in a tertiary referral center: A magnetic resonance cholangiopancreaticographic study. AB - BACKGROUND: Knowledge about anatomic variations in intrahepatic biliary ducts (IHBD) is relevant for performing biliary drainage and for avoiding bile duct injury during cholecystectomy and liver resections. Low insertion of cystic duct (LICD) is a common anatomic variant. Pancreas divisum is the commonest congenital anomaly of pancreas; it has been causally linked with recurrent acute pancreatitis (RAP). METHODS: Magnetic resonance cholangiopancreaticography (MRCP) images of 500 consecutive patients were reviewed for anatomic variants of IHBD, cystic duct, and pancreatic duct. RESULTS: Anatomy of IHBD could be evaluated in 458 MRCP's, of these 301 (65.72 %) had 'typical' anatomy. The variant in 157 persons included 'triple confluence' in 56 (12.23 %), 'right posterior segmental duct (RPSD) draining to left hepatic duct (LHD)' in 64 (14 %), 'RPSD to common hepatic duct (CHD)' in 20 (4.4 %), 'RPSD to cystic duct' in 2 (0.4 %), 'accessory duct to CHD' in 3 (0.7 %), 'accessory duct to right hepatic duct (RHD)' in 1 (0.2 %), 'segment 2 and 3 separately to CHD' in 1 (0.2 %), and complex variants in 10 (2.2 %). Cystic duct could be evaluated in 338 patients; of these, 15 (4.4 %) had LICD. Patients with RAP had pancreas divisum more often than those without any pancreatic disease, (-/-,10 % and -/-, 0.8 %; p = 0.004). CONCLUSIONS: Nearly one third of MRCPs showed atypical IHBD pattern with RPSD draining to LHD being the commonest. LICD was the most common cystic duct variant. Pancreas divisum was more frequent in patients with RAP than in persons without pancreatic disease. PMID- 27660207 TI - Fatty Acid de Novo Synthesis in Adult Intrauterine Growth-Restricted Offspring, and Adult Male Response to a High Fat Diet. AB - Intrauterine growth restriction (IUGR) with rapid catch-up growth leads to adult obesity and insulin resistance. We have previously shown that IUGR male rats demonstrated increased de novo fatty acid synthesis in the subcutaneous (SC) fat, but not the visceral fat, during the nursing period prior to the onset of obesity. Young IUGR females do not exhibit the same increase. We further hypothesized that in male IUGR offspring, de novo synthesis is a programmed intrinsic effect that persists to adulthood and does not suppress in response to a high fat diet. We measured fatty acid de novo synthesis in IUGR adult males (6 months) using deuterium-enriched drinking water as a stable isotope tracer, then further studied the response after consumption of an isocaloric high fat diet. Baseline de novo synthesis in adult females was also studied at age 9 months. Males demonstrated increased baseline de novo synthesis in both SC fat and visceral fat. Correspondingly, SC and visceral fat protein expression of lipogenic enzymes acetyl-coA carboxylase-alpha (ACCalpha) and fatty acid synthase were upregulated. After the isocaloric high fat diet, de novo synthesis was suppressed such that no differences remained between the two groups, although, IUGR SC fat demonstrated persistently increased lipogenic protein expression. In contrast, de novo synthesis among adult females is not impacted in IUGR. In conclusion, enhancement of male IUGR SC fat de novo synthesis appears to be an early consequence of metabolic programming, whereas enhancement in visceral fat appears to be a later consequence. PMID- 27660209 TI - Efficacy and Safety of Pregabalin for the Treatment of Neuropathic Pain in Patients Undergoing Hemodialysis. AB - OBJECTIVE: Pregabalin is a gamma aminobutyric acid derivative administered for neuropathic pain. It binds to alpha2delta subunits of voltage-dependent calcium channels, and inhibits calcium inflow of synapses and the release of excitatory neurotransmitters. This study investigated the efficacy and safety of pregabalin in patients with peripheral neuropathic pain undergoing maintenance hemodialysis. METHODS: This study was a prospective, open-label, single-arm, multi-center trial. Patients were treated with an initial dose of pregabalin at 25 mg; this was then increased up to a maximum of 150 mg depending on the patient during a 12 week study period. Visual Analog Scale, Eight-Item Short Form Health Survey (SF 8), and laboratory data were collected at baseline and the end of the study. RESULTS: A total of 45 patients with peripheral neuropathic pain were included, of whom 35 patients were analyzed. The final mean dose of pregabalin was 50.7 mg daily. Mean Visual Analog Scale scores significantly decreased from 52.4 mm at baseline to 34.1 mm at the end of the study (p < 0.0001). Scores for all eight categories of the SF-8 significantly increased compared with baseline (p < 0.05). Both physical and mental component summary scores of the SF-8 also significantly increased (p < 0.05). Ten patients were withdrawn from the study because of drowsiness, dizziness, and invalidity; however, no serious adverse drug reactions were recorded. CONCLUSIONS: If adverse effects are carefully monitored and the administered dosage prudently determined, pregabalin can be an effective treatment for peripheral neuropathic pain in patients undergoing hemodialysis. TRIAL REGISTRATION: UMIN000023117. PMID- 27660208 TI - Expression and localization of forkhead box protein FOXJ1 in S100beta-positive multiciliated cells of the rat pituitary. AB - S100beta-positive cells exist in the marginal cell layer (MCL) of the adenohypophysis and follicle structure in the parenchyma of anterior lobe (ALFS) in pituitary. They have multiple functions as phagocytes or cells that regulate hormone secretion. Majority of S100beta-positive cells in the adenohypophysis express sex determining region Y-box 2 protein (SOX2), a stem cell marker; therefore, S100beta/SOX2 double positive cells are also considered as one type of stem/progenitor cells. MCL and ALFS are consisting of morphologically two types of cells, i.e., multiciliated cells and non-ciliated cells. However, the relationship between the S100beta-positive cells and multiciliated cells in the pituitary is largely unknown. In the present study, we first immunohistochemically verified the feature of multiciliated cells in MCL and ALFS. We then examined the expression patterns of FOXJ1, an essential expression factor for multiciliated cell-differentiation, and SOX2 in the S100beta-positive multiciliated cells by in situ hybridization and immunohistochemistry. We identified anew the S100beta/SOX2/FOXJ1 triple positive multiciliated cells, and revealed that they were dispersed throughout the MCL and ALFS. These results indicate that the MCL and ALFS are consisting of morphologically and functionally distinct two types of cells, i.e., S100beta/SOX2 double positive non-ciliated cells and S100beta/SOX2/FOXJ1 triple positive multiciliated cells. PMID- 27660210 TI - Synchronous fluorescence spectroscopy combined with two-dimensional correlation and principle component analysis to characterize dissolved organic matter in an urban river. AB - Synchronous fluorescence spectroscopy (SFS) combined with two-dimensional correlation and principle component analysis (PCA) can provide an excellent challenge to capture fluorescent components of dissolved organic matter (DOM) and reveal its spatial variations in an urban river. Water samples were collected from Baitapuhe River along human impact gradient, i.e., the rural, town, and urban regions. DOM in Baitapuhe River was composed of protein-like, microbial humic-like, fulvic-like, and humic-like fluorescent components. The protein-like was the dominant component, which consisted of tyrosine-like and tryptophan-like components. In the rural region, the variation of the microbial humic-like was higher than that of the protein-like according to the band changing order of 335 > 281 nm, and both components changed in the same direction. In the town region, the variation of the microbial humic-like was the highest followed by the protein like and fulvic-like on the basis of the changing band order of 335 -> 281 -> 369 nm, and these components varied in the same trend too. In the urban region, the variation of the protein-like was the highest, followed by the microbial humic like, fulvic-like, and humic-like based on the changing band order of 282 -> 335 > 369 -> 470 nm, and the protein-like variation was opposite to the other components. The SFS combined with PCA and two-dimensional correlation can be used as a powerful tool in investigating fluorescent components of DOM and revealing spatial variations of these fluorescent components. PMID- 27660211 TI - Spatio-temporal variability of dissolved organic nitrogen (DON), carbon (DOC), and nutrients in the Nile River, Egypt. AB - Increases in human activity have resulted in enhanced anthropogenic inputs of nitrogen (N) and carbon (C) into the Nile River. The Damietta Branch of the Nile is subject to inputs from industrial, agricultural, and domestic wastewater. This study investigated the distribution and seasonality of dissolved organic nitrogen (DON), dissolved organic carbon (DOC), and nutrients in the Nile Damietta Branch. Water samples were collected from 24 sites between May 2009 and February 2010. Dissolved organic nitrogen concentrations averaged 251 +/- 115 MUg/l, with a range of 90.2-671 MUg/l, and contributed 40.8 +/- 17.7 % to the total dissolved nitrogen (TDN) pool. Relative to autumn and winter, DON was a larger fraction of the TDN pool during spring and summer indicating the influence of bacterioplankton on the nitrogen cycle. Concentrations of DOC ranged from 2.23 to 11.3 mg/l with an average of 5.15 +/- 2.36 mg/l, reflecting a high organic matter load from anthropogenic sources within the study area, and were highest during autumn. Higher values of biochemical oxygen demand (BOD), chemical oxygen demand (COD), DON, nitrate, and phosphate occurred downstream of the Damietta Branch and were probably due to anthropogenic inputs to the Nile from the Damietta district. A bacterial incubation experiment indicated that 52.1-95.0 % of DON was utilized by bacteria within 21 days. The decrease in DON concentration was accompanied by an increase in nitrate concentration of 54.8-87.3 %, presumably through DON mineralization. Based on these results, we recommend that water quality assessments consider DON and DOC, as their omission may result in an underestimation of the total organic matter load and impact. PMID- 27660212 TI - Heterogeneous areas-identification of outliers and calculation of soil sampling uncertainty using the modified RANOVA method. AB - We modified the robust analysis of variance (RANOVA) method to calculate sampling uncertainty of selected trace elements determined in soil samples from two heterogeneous remote historic metal ore mining areas. Classical RANOVA is down weighting the outlying values by replacing them during the calculation process with mean +/- c.sigma r . Because the arithmetic mean is greatly influenced by outliers, it cannot represent a robust statistic. The main novel contribution of this work is use of median value that is independent on outliers and replace all extreme values during the calculation process with median +/- 2.sigma r . In our work, 18 duplicate, composite soil samples were collected, digested with aqua regia in a closed microwave system, and analyzed twice for selected trace elements. To extract homogenous groups within sampling areas and make the results more accessible for interpretation, a cluster analysis was done. Subsequently, histograms of each element were prepared and statistical tests were applied to determine the normal distribution of datasets. For abnormally distributed elements, the outlying values were identified by four different methods: boxplot, mean +/- c.sigma r , mean +/- c.sigma, and median +/- 2.sigma r . For five elements, the amount of outliers identified by the median +/- 2.sigma r procedure was less than 10 %, and for these elements, the sampling uncertainty was computed using a modified RANOVA method. The sampling uncertainty computed with this method was 28.9 % for Cd, 15.2 % for Co, 14.5 % for Mn, 12.7 % for Ni, and 16.3 % for Zn, whereas that computed with a traditional model was 16.7 % for Cd, 9.2 % for Co, 20.5 % for Mn, 17.9 % for Ni, and 16.3 % for Zn. PMID- 27660213 TI - Viral Diversity, Prey Preference, and Bartonella Prevalence in Desmodus rotundus in Guatemala. AB - Certain bat species serve as natural reservoirs for pathogens in several key viral families including henipa-, lyssa-, corona-, and filoviruses, which may pose serious threats to human health. The Common Vampire Bat (Desmodus rotundus), due to its abundance, sanguivorous feeding habit involving humans and domestic animals, and highly social behavioral ecology, may have an unusually high potential for interspecies disease transmission. Previous studies have investigated rabies dynamics in D. rotundus, yet the diversity of other viruses, bacteria, and other microbes that these bats may carry remains largely unknown. We screened 396 blood, urine, saliva, and fecal samples from D. rotundus captured in Guatemala for 13 viral families and genera. Positive results were found for rhabdovirus, adenovirus, and herpesvirus assays. We also screened these samples for Bartonella spp. and found that 38% of individuals tested positive. To characterize potential for interspecies transmission associated with feeding behavior, we also analyzed cytochrome B sequences from fecal samples to identify prey species and found that domestic cattle (Bos taurus) made up the majority of blood meals. Our findings suggest that the risk of pathogen spillover from Desmodus rotundus, including between domestic animal species, is possible and warrants further investigation to characterize this microbial diversity and expand our understanding of foraging ecology in their populations. PMID- 27660214 TI - Aspergillus fumigatus DBM 4057 biofilm formation is inhibited by chitosan, in contrast to baicalein and rhamnolipid. AB - The biofilms of filamentous-forming fungi are a novel and still insufficiently understood research topic. We have studied Aspergillus fumigatus, an ubiquitous opportunistic pathogenic fungus, as a representative model for a study of biofilm formation by filamentous fungi and for assessing the potential anti-biofilm activity of natural substances. The activity of antibiotic amphotericin B and selected natural substances: baicalein, chitosan and rhamnolipid was studied. The minimum suspension inhibitory concentrations (MIC) were determined and the biofilm susceptibility was investigated by determining the metabolic activity of sessile cells (XTT assay) and total biofilm biomass (crystal violet staining). Significant time-dependent differences in substances' anti-biofilm activity were observed. Images of A. fumigatus biofilm were obtained by Cellavista automatic light microscope and spinning disc confocal microscopy. Baicalein and rhamnolipid were not found as suitable substances for inhibition of the A. fumigatus biofilm formation, as neither of the substances inhibited the sessile cells metabolic activity or the total biofilm biomass even at tenfold MIC after 48 h. In contrast, chitosan at 10 * MIC (25 ug mL-1), suppressed the biofilm metabolic activity by 90 % and the total biofilm biomass by 80 % even after 72 h of cultivation. Amphotericin B inhibited only 14 % of total biofilm biomass (crystal violet staining) and 35 % of metabolic activity (XTT assay) of adherent cells under the same conditions. Our results therefore suggest chitosan as potential alternative for treating A. fumigatus biofilm-associated infections. PMID- 27660216 TI - Delivery of Fluorescent Nanoparticles to the Brain. AB - Nanotechnology applications in neuroscience promises to deliver significant scientific and technological breakthroughs, providing answers to unresolved questions regarding the processes occurring in the brain. In this perspective, we provide a short background on two distinct fluorescent nanoparticles and summarize several studies focussed on achieving delivery of these into the brain and their interaction with brain tissue. Furthermore, we discuss challenges and opportunities for further development of nanoparticle-based therapies for targeting delivery of drugs across the blood-brain barrier. PMID- 27660215 TI - Multitasking Microglia and Alzheimer's Disease: Diversity, Tools and Therapeutic Targets. AB - Given the importance of microglia to inflammatory, phagocytic and synaptic modulatory processes, their function is vital in physiological and pathological brain. The impairment of microglia in Alzheimer's disease has been demonstrated on genetic, epigenetic, transcriptional and functional levels using unbiased systems level approaches. Recent studies have highlighted the immense phenotypic diversity of microglia, including the ability to adopt distinct and dynamic phenotypes in ageing and disease. We review the origins and functions of healthy microglia and the established and emerging models and techniques available for their study. Furthermore, we highlight recent advances on the role, heterogeneity and dysfunction of microglia in Alzheimer's disease and discuss the potential for therapeutic interventions targeting microglia. Microglia-selective molecular fingerprints will guide detailed functional analysis of microglial subsets and may aid in the development of therapies specifically targeting microglia. PMID- 27660218 TI - Circulating MicroRNAs as Novel Diagnostic Biomarkers for Very Early-onset (<=40 years) Coronary Artery Disease. AB - OBJECTIVE: Very early-onset coronary artery disease (CAD) is a great challenge in cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs (miRNAs) could be used as potential biomarkers for patients with very early-onset CAD. METHODS: We performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patients with very early-onset CAD and 40 angiography normal controls. RESULTS: A total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls (P<0.05). The areas under the receiver operating characteristic curve for these miRNAs were 0.824 (95% CI, 0.731-0.917; P<0.001), 0.758 (95% CI, 0.651-0.864; P<0.001), 0.753 (95% CI, 0.643-0.863; P<0.001), and 0.782 (95% CI, 0.680-0.884; P<0.001), respectively, in the validation set. CONCLUSION: To our knowledge, this is an advanced study to report about four serum miRNAs (miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD. PMID- 27660217 TI - Cholinergic and Dopaminergic Alterations in Nigrostriatal Neurons Are Involved in Environmental Enrichment Motor Protection in a Mouse Model of Parkinson's Disease. AB - Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, being characterized by dopaminergic neurodegeneration of substantia nigra pars compacta. PD pharmacotherapy has been based on dopamine replacement in the striatum with the dopaminergic precursor 3,4-dihydroxyphenylalanine (L-DOPA) and/or with dopaminergic agonists, alongside anticholinergic drugs in order to mitigate the motor abnormalities. However, these practices neither prevent nor stop the progression of the disease. Environmental enrichment (EE) has effectively prevented several neurodegenerative processes, mainly in preclinical trials. Several studies have demonstrated that EE induces biological changes, bearing on cognitive enhancement, neuroprotection, and on the attenuation of the effects of stress, anxiety, and depression. Herein, we investigated whether EE could prevent the motor, biochemical, and molecular abnormalities in a murine model of PD induced by 1-methyl-4-phenyl-2,3-dihydropyridine (MPTP). Our results show that EE does not prevent the dopaminergic striatal depletion induced by MPTP, despite having averted the MPTP-induced hyperlocomotion. However, it was able to slow down and avoid, respectively, the 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion. Analysis of dopaminergic mRNA alterations in the midbrain showed that D1R expression was increased by MPTP, while the normal expression level of this receptor was restored by EE. As for the cholinergic system, MPTP led to a decrease in the ChAT gene expression while increasing the expression of both AChE and M1R. EE attenuated and prevented respectively-ChAT and M1R gene expression alterations triggered by MPTP in the midbrain. Overall, our data brings new evidence supporting the neuroprotective potential of EE in PD, focusing on the interaction between dopaminergic and cholinergic systems. PMID- 27660219 TI - Alcohol Drinking, Dyslipidemia, and Diabetes: A Population-based Prospective Cohort Study among Inner Mongolians in China. AB - OBJECTIVE: No previous studies have evaluated the association between dyslipidemia, alcohol drinking, and diabetes in an Inner Mongolian population. We aimed to evaluate the co-effects of drinking and dyslipidemia on diabetes incidence in this population. METHODS: The present study was based on 1880 participants from a population-based prospective cohort study among Inner Mongolians living in China. Participants were classified into four subgroups according to their drinking status and dyslipidemia. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to evaluate the association between alcohol drinking, dyslipidemia, and diabetes. RESULTS: During the follow-up period, 203 participants were found to have developed diabetes. The multivariable-adjusted odds ratios (95% confidence interval) for the incidence of non-dyslipidemia/drinkers, dyslipidemia/non drinkers, and dyslipidemia/drinkers in diabetic patients were 1.40 (0.82-2.37), 1.73 (1.17-2.55), and 2.31 (1.38-3.87), respectively, when compared with non dyslipidemia/non-drinkers. The area under the ROC curve for a model containing dyslipidemia and drinking status along with conventional factors (AUC=0.746) was significantly (P=0.003) larger than the one containing only conventional factors (AUC=0.711). CONCLUSION: The present study showed that dyslipidemia was an independent risk factor for diabetes, and that drinkers with dyslipidemia had the highest risk of diabetes in the Mongolian population. These findings suggest that dyslipidemia and drinking status may be valuable in predicting diabetes incidence. PMID- 27660220 TI - Biological Effects of Cloth Containing Specific Ore Powder in Patients with Pollen Allergy. AB - OBJECTIVE: The custom-homebuilding company, Cosmic Garden Co. Ltd., located in Okayama City, Japan was established in 1997 and uses specific natural ore powder (SNOP) in wall materials and surveys customers in order to improve allergic symptoms. METHODS: To investigate the biological effects of SNOP, patients with a pollen allergy were recruited to stay in a room surrounded by cloth containing SNOP (CCSNOP), and their symptoms and various biological parameters were compared with those of individuals staying in a room surrounded by control non-woven cloth (NWC). Each stay lasted 60 min. Before and immediately after the stay, a questionnaire regarding allergic symptoms, as well as POMS (Profile of Mood Status) and blood sampling, was performed. Post-stay minus pre-stay values were calculated and compared between CCSNOP and NWC groups. RESULTS: Results indicated that some symptoms, such as nasal obstruction and lacrimation, improved, and POMS evaluation showed that patients were calmer following a stay in CCSNOP. Relative eosinophils, non-specific Ig E, epidermal growth factor, monocyte chemotactic protein-1, and tumor necrosis factor-alpha increased following a stay in CCSNOP. CONCLUSION: This ore powder improved allergic symptoms, and long-term monitoring involving 1 to 2 months may be necessary to fully explore the biological and physical effects of SNOP on allergic patients. PMID- 27660221 TI - Structural Modulation of Gut Microbiota in Rats with Allergic Bronchial Asthma Treated with Recuperating Lung Decoction. AB - OBJECTIVE: To investigate whether recuperating lung decoction (RLD) can modulate the composition of gut microbiota in rats during asthma treatment. METHODS: Fifteen Sprague-Dawley rats were divided randomly and equally into control group, model group, dexamethasone (DEX) group, RLD medium-dose group, and RLD high-dose group. The asthma model was established in all groups, except for the control group. The rats in the DEX and RLD groups were treated orally with DEX and RLD, respectively. The rats in the control and model groups were treated orally with 0.9% saline. The intestinal bacterial communities were compared among groups using 16S rRNA gene amplification and 454 pyrosequencing. RESULTS: The microbial flora differed between the control and model groups, but the flora in the RLD groups was similar to that in the control group. No significant differences were observed between the RLD high-dose and medium-dose groups. RLD treatment resulted in an increase in the level beneficial bacteria in the gut, such as Lactobacillus and Bifidobacterium spp. CONCLUSION: Oral administration of RLD increased the number of intestinal lactic acid-producing bacteria, such as Lactobacillus and Bifidobacterium, in asthma model rats. PMID- 27660222 TI - Expression of Peroxiredoxins and Pulmonary Surfactant Protein A Induced by Silica in Rat Lung Tissue. AB - Silicosis is one of the most serious occupational diseases in China and dates back to centuries ago. In this study, we successfully established a rat model of silicosis by intratracheal silica injection for 28 days and determined hydroxyproline levels to evaluate collagen metabolism in lung homogenates. Oxidative stress status was evaluated by detecting catalase and glutathione peroxidase activities. Expression levels of peroxiredoxins (Prx I and Prx VI) were detected by Western blotting. Pulmonary surfactant protein A (SP-A) levels in rat serum and lung tissue were analyzed by ELISA, and SP-A and Prx expression levels in lung tissues were detected by immunohistochemistry. The results suggest that Prx proteins may be involved in pulmonary fibrosis induced by silica. Downregulation of SP-A expression caused due to silica is an important factor in the occurrence and development of silicosis. PMID- 27660223 TI - 8-isoprostane as Oxidative Stress Marker in Coal Mine Workers. AB - This study was to investigate whether working in conditions of elevated concentrations of mine gases (CO2, CO, CH4, DMS) and dust may result in oxidative stress. Coal miners (n=94) from the Velenje Coal mine who were arranged into control group and three groups according to a number of consecutive working days. 8-isoprostane as a biological marker of oxidative stress was measured in exhaled breath condensate (EBC). Miners who worked for three consecutive days had higher 8-isoprostane values in EBC compared to the control group. Gas/dust concentrations and exposure time of a single/two day shift seem too low to trigger immediate oxidative stress. PMID- 27660225 TI - Evaluation of Xpert MTB/RIF for the Diagnosis of Extrapulmonary Tuberculosis in China. AB - We evaluate the performance of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis (EPTB) in China. The performance of Xpert was evaluated compared to the composite reference standard (CRS), drug susceptibility testing (DST), and imaging examination. The overall sensitivity and specificity of Xpert were 64.1% (195/304) and 100% (24/24), respectively, using CRS as the gold standard. The sensitivity was significantly higher than that of culture for pus (P<0.05). The proportion of EPTB-positive cases diagnosed by imaging was two times more than that diagnosed using Xpert; however, 6 out of 19 cases may have been overdiagnosed by imaging. Compared to phenotypic DST, the sensitivity and specificity of Xpert were 80% (12/15) and 100% (75/75), respectively. Considering its high sensitivity and specificity, Xpert MTB/RIF may be used as a rapid initial test for EPTB diagnosis, and may also support a quicker decision on the treatment regimen. The combination of imaging and Xpert testing could provide high efficiency and accurate diagnosis of suspected EPTB. PMID- 27660224 TI - Effect of Smo SiRNA-mediated Hedgehog Signaling Pathway Inhibition on Palatal Fusion. AB - We used Smo siRNA to inhibit hedgehog signaling pathway in embryonic day (E) 13 palatal shelves in organ culture. SiRNA 4 was chosen as the most efficient from four synthesized Smo siRNAs. Palatal shelf fusion rate of 4 MUg/mL cyclopamine group was the lowest and significantly lower than that of blank control group (P<0.05), and that of siRNA 4 group was also lower than that of blank control group (P=0.183). At 48 h after transfection, Smo protein level of siRNA 4 group was 64.8% lower than that of blank control group (P<0.05), and Gli1 protein level of 4 MUg/mL cyclopamine group was 68.9% lower than that of blank control group (P<0.05). Hedgehog signaling pathway inhibition decreased palatal fusion in organ culture, probably owing to downregulation of Smo and Gli1 proteins. PMID- 27660226 TI - Distribution Characteristics of Spermophilus dauricus in Manchuria City in China in 2015 through '3S' Technology. AB - Plague is a virulent infectious disease in China. In this study, '3S' technology was used to perform spatial autocorrelation analysis and spatial interpolation analysis for Spermophilus dauricus (S. Dauricus, a species of ground squirrel) captured in Manchuria City in 2015. The results were visually inspected. During the two-month (May to July) plague surveillance in 2015, 198 S. dauricus individuals were captured in the study area in Manchuria City (48 monitoring areas) by using a day-by-day catching method. Spatial autocorrelation was conducted using the ArcGIS software, and the following significantly different results were obtained: Moran's I=0.228472, Z-score=2.889126, and P<0.05. Thus, a spatial aggregation was observed. In 2015, the distribution of S. dauricus diminished from west to east and from north to south of Manchuria. Geo Detector software was used to analyze the habitat factors affecting the spatial distribution of S. dauricus. This highly clustered species mainly exists in suburban communities, construction sites, and areas surrounding factories. In future studies, plague surveillances should be performed in areas around Manchuria and Zhalainuoer. PMID- 27660227 TI - Viral Contamination Source in Clinical Microbiology Laboratory. AB - To understand the potential causes of laboratory-acquired infections and to provide possible solutions that would protect laboratory personnel, samples from a viral laboratory were screened to determine the main sources of contamination with six subtypes of Rhinovirus. Rhinovirus contamination was found in the gloves, cuffs of protective wear, inner surface of biological safety cabinet (BSC) windows, and trash handles. Remarkably, high contamination was found on the inner walls of the centrifuge and the inner surface of centrifuge tube casing in the rotor. Spilling infectious medium on the surface of centrifuge tubes was found to contribute to contamination of centrifuge surfaces. Exposure to sodium hypochlorite containing no less than 0.2 g/L available chlorine decontaminated the surface of the centrifuge tubes from Rhinovirus after 2 min. PMID- 27660229 TI - Morphometric characterization of the human portal and hepatic venous trees: A quantitative support to the liver micro-anatomic models free of subunits. AB - Conventional models of liver microanatomy assume the presence of subunits. Nevertheless, some researchers propose that the liver is a continuous structure, free of these subunits, but with a characteristic vascular pattern. The present study describes a morphometric analysis of portal and hepatic veins in 50 human autopsy non-pathological liver samples. The main objective was to measure three proportions: 1. portal tracts / hepatic veins, 2. distributing portal veins / distributing hepatic veins and 3. terminal portal veins / terminal hepatic veins. These ratios were compared with the traditional microcirculatory liver models. Our material comprised 3,665 portal veins and 3,761 hepatic veins. The minimum diameter of half of the venous vessels of both types belongs to the interval (25MUm , 60MUm), given that 1881 portal veins (49.434%) and 1924 hepatic veins (50.565%) fall within this interval. We have statistically shown with the chi2 test (alpha=0.990) that the portal and hepatic veins belonging to the interval (25MUm , 400MUm) (distributing veins) had an identical proportion. If the portal and hepatic veins are arranged according to the principle of interdigitation of Takashasi (1970), there should be an almost identical number of both types of veins. Our results contradict the presumably numeric preponderance of distributing portal veins with regard to the distributing hepatic veins that is inherent in the models of Kiernan, Matsumoto and Rappaport. PMID- 27660228 TI - Risk of Treatment Failure in Patients with Drug-susceptible Pulmonary Tuberculosis in China. AB - The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis (PTB) was to provide reference data to help develop a disease control strategy. Participants were recruited in eight provinces of China from October 2008 to December 2010. A total of 1447 patients with drug-susceptible PTB and older than 15 years of age were enrolled. Demographic characteristics, bacteriological test results, and patient outcome, i.e., cure or treatment failure were recorded and compared using the chi square or Fisher's exact tests. Multivariate logistic regression was used to identify factors associated with risk of treatment failure. Of the 1447 patients who were enrolled, 1349 patients (93.2%) were successfully treated and 98 (6.8%) failed treatment. Failure was significantly associated with age 365 years [odds ratio (OR)=2.522, 95% confidence interval (CI): (1.097-5.801)], retreatment [OR=2.365, 95% CI: (1.276-4.381)], missed medicine [OR=1.836, 95% CI: (1.020 3.306)], treatment not observed [OR=1.879 95% CI: (1.105-3.195)], and positive culture result after the first [OR=1.971, 95% CI: (1.080-3.597)] and second month [OR=4.659, 95% CI: (2.590-8.382)]. The risk factors associated with treatment failure were age 365 years, retreatment, missed medication, treatment not observed, and positive culture at the end of month 1 or month 2. These risk factors should be monitored during treatment and interventions carried out to reduce or prevent treatment failure and optimize treatment success. PMID- 27660230 TI - Epithelioid hemangioma of bone: a report of two special cases and a literature review. AB - Intraosseous epithelioid hemangioma (EH) is a rare intermediate vascular neoplasm, characterized by locally aggressive and rarely metastasizing behavior. Occasionally, EH of bone can behave strangely and may simulate malignant neoplasm. Here, we report two cases of EH of bone. Of interest was the fact that the computed tomography and magnetic resonance images from one case showed an osteolytic lesion in the right scapula, with multiple swollen lymph nodes in the right supraclavicular and axillary areas. Another patient exhibited a local recurrence in the cervical vertebrae. The initial radiological diagnosis of both cases was metastatic tumor. EH should be included in the differential diagnosis of a radiographic osteolytic lesion with an aggressive appearance. Also, we reviewed the literature that reported EH of bone and summarized their radiological appearances. The cases of EH of bone that exhibited involvement of regional or draining lymph nodes were also summarized. PMID- 27660231 TI - Detection of incorrect manufacturer labelling of hip components. AB - We describe the case of a 53-year-old man who underwent a left metal-on-metal hip resurfacing in 2015. Component size mismatch (CSM) was suspected because of the patient's immediate post-operative mechanical symptoms and high metal ion levels. Surgical notes indicated the appropriate combinations of implants were used. However, we detected a mismatch using computed tomography. Revision was performed and subsequent measurements of explanted components confirmed the mismatch. To our knowledge, this case is the first report of a CT method being used in a patient to pre-operatively identify CSM. PMID- 27660233 TI - Role of K13 Mutations in Artemisinin-Based Combination Therapy. PMID- 27660232 TI - Rice bran protein hydrolysates reduce arterial stiffening, vascular remodeling and oxidative stress in rats fed a high-carbohydrate and high-fat diet. AB - PURPOSE: Rice bran protein hydrolysates (RBPH) contain highly nutritional proteins and antioxidant compounds which show benefits against metabolic syndrome (MetS). Increased arterial stiffness and the components of MetS have been shown to be associated with an increased risk of cardiovascular disease. This study aimed to investigate whether RBPH could alleviate the metabolic disorders, arterial stiffening, vascular remodeling, and oxidative stress in rats fed a high carbohydrate and high-fat (HCHF) diet. METHODS: Male Sprague-Dawley rats were fed either a standard chow and tap water or a HCHF diet and 15 % fructose solution for 16 weeks. HCHF rats were treated orally with RBPH (250 or 500 mg/kg/day) for the final 6 weeks of the experimental period. RESULTS: Rats fed with HCHF diet had hyperglycemia, insulin resistance, dyslipidemia, hypertension, increased aortic pulse wave velocity, aortic wall hypertrophy and vascular remodeling with increased MMP-2 and MMP-9 expression. RBPH supplementation significantly alleviated these alterations (P < 0.05). Moreover, RBPH reduced the levels of angiotensin-converting enzyme (ACE) and tumor necrosis factor-alpha in plasma. Oxidative stress was also alleviated after RBPH treatment by decreasing plasma malondialdehyde, reducing superoxide production and suppressing p47phox NADPH oxidase expression in the vascular tissues of HCHF rats. RBPH increased plasma nitrate/nitrite level and up-regulated eNOS expression in the aortas of HCHF-diet fed rats, indicating that RBPH increased NO production. CONCLUSION: RBPH mitigate the deleterious effects of HCHF through potential mechanisms involving enhanced NO bioavailability, anti-ACE, anti-inflammatory and antioxidant properties. RBPH could be used as dietary supplements to minimize oxidative stress and vascular alterations triggered by MetS. PMID- 27660235 TI - Trends of Media Coverage on Human Papillomavirus Vaccination in Japanese Newspapers. AB - A sensational newspaper article concerning a possible adverse reaction to the human papillomavirus (HPV) vaccine was published in March 2013 in Japan. In June 2013, the Japanese government suspended their proactive recommendation for vaccination, despite the lack of proof for a causal relationship. We searched Nikkei Telecom 21, the largest newspaper database in Japan, for articles published from January 2011 to December 2015 to evaluate the characteristics of newspaper publications about human papillomavirus vaccination. We identified 1138 HPV vaccine-related articles. Compared with those published before March 2013, articles concerning human papillomavirus vaccination after March 2013 were more likely to include adverse reaction-related and authority-related keywords; articles that included efficacy-related keywords decreased significantly. Negative-negative and negative-neutral articles became more frequent, and positive-positive and positive-neutral articles were less frequent. A sensational case report shaped the tone of negative media coverage as a catalyst, regardless of scientific statements from health authorities. PMID- 27660234 TI - Suboptimal Adherence to Combination Antiretroviral Therapy Is Associated With Higher Levels of Inflammation Despite HIV Suppression. AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals exhibit residual inflammation regardless of virologic suppression. We evaluated whether suboptimal adherence to combination antiretroviral therapy (cART) is associated with greater residual inflammation than optimal adherence, despite virologic suppression. METHODS: Longitudinal self-reported cART adherence data and serum concentrations of 24 biomarkers of inflammation and immune activation were measured at the same study visit in HIV RNA-suppressed (<50 copies/mL) HIV infected men in the Multicenter AIDS Cohort Study from 1998 to 2009. Associations between dichotomized 6-month (<100% vs 100%) and categorized 4-day (<85%, 85% 99%, and 100%) cART adherence with biomarker concentrations were evaluated. RESULTS: A total of 912 men provided 2816 person-visits with documented plasma HIV RNA suppression. In adjusted models, person-visits at which <100% cART 6 month adherence was reported had higher concentrations of interleukin 2, 6, and 10, interferon gamma, tumor necrosis factor alpha, and C-reactive protein than person-visits at which 100% cART adherence (P < .05) was reported. These same differences were observed in person-visits reporting <85% versus 100% 4-day cART adherence, but not in visits reporting 85%-99% versus 100% cART adherence. After adjustment for multiple comparisons, tumor necrosis factor alpha remained significantly higher (11% increase; P < .001) in person-visits at which <100% adherence was reported. CONCLUSIONS: Higher concentrations of inflammatory biomarkers were observed among HIV RNA-suppressed men who reported <100% cART adherence than among more adherent men. Residual HIV replication (ie, below the limit of detection), more likely among men with suboptimal adherence, is a plausible mechanism. Whether improving cART adherence could affect residual inflammation and associated morbidity and mortality rates should be investigated. PMID- 27660236 TI - Suboptimal Viral Suppression Rates Among HIV-Infected Children in Low- and Middle Income Countries: A Meta-analysis. AB - BACKGROUND: The 90-90-90 goal to achieve viral suppression in 90% of all human immunodeficiency virus (HIV)-infected people on antiretroviral treatment (ART) is especially challenging in children. Global estimates of viral suppression among children in low- and middle-income countries (LMICs) are lacking. METHODS: We searched for randomized controlled trials and observational studies and analyzed viral suppression rates among children started on ART during 3 time periods: early (2000-2005), intermediate (2006-2009), and current (2010 and later), using random effects meta-analysis. RESULTS: Seventy-two studies, reporting on 51 347 children (aged <18 years), were included. After 12 months on first-line ART, viral suppression was achieved by 64.7% (95% confidence interval [CI], 57.5-71.8) in the early, 74.2% (95% CI, 70.2-78.2) in the intermediate, and 72.7% (95% 62.6 82.8) in the current time period. Rates were similar after 6 and 24 months of ART. Using an intention-to-treat analysis, 42.7% (95% CI, 33.7-51.7) in the early, 45.7% (95% CI, 33.2-58.3) in the intermediate, and 62.5% (95% CI, 53.3 72.6) in the current period were suppressed. Long-term follow-up data were scarce. CONCLUSIONS: Viral suppression rates among children on ART in LMICs were low and considerably poorer than those previously found in adults in LMICs and children in high-income countries. Little progress has been made in improving viral suppression rates over the past years. Without increased efforts to improve pediatric HIV treatment, the 90-90-90 goal for children in LMIC will not be reached. PMID- 27660237 TI - Placenta plays a critical role in maternal-fetal resource allocation. PMID- 27660238 TI - Smelling better with chloride. PMID- 27660240 TI - Neurons versus Networks: The Interplay between Individual Neurons and Neural Networks in Cognitive Functions. AB - The main paradigm of cognitive neuroscience is the connectionist concept postulating that the higher nervous activity is performed through interactions of neurons forming complex networks, whereas the function of individual neurons is restricted to generating electrical potentials and transmitting signals to other cells. In this article, I describe the observations from three fields neurolinguistics, physiology of memory, and sensory perception-that can hardly be explained within the constraints of a purely connectionist concept. Rather, these examples suggest that cognitive functions are determined by specific properties of individual neurons and, therefore, are likely to be accomplished primarily at the intracellular level. This view is supported by the recent discovery that the brain's ability to create abstract concepts of particular individuals, animals, or places is performed by neurons ("concept cells") sparsely distributed in the medial temporal lobe. PMID- 27660239 TI - Direct observation of light-driven, concerted electron-proton transfer. AB - The phenols 4-methylphenol, 4-methoxyphenol, and N-acetyl-tyrosine form hydrogen bonded adducts with N-methyl-4, 4'-bipyridinium cation (MQ+) in aqueous solution as evidenced by the appearance of low-energy, low-absorptivity features in UV visible spectra. They are assigned to the known examples of optically induced, concerted electron-proton transfer, photoEPT. The results of ultrafast transient absorption measurements on the assembly MeOPhO-H---MQ+ are consistent with concerted EPT by the instantaneous appearance of spectral features for MeOPhO.-- H-MQ+ in the transient spectra at the first observation time of 0.1 ps. The transient decays to MeOPhO-H---MQ+ in 2.5 ps, accompanied by the appearance of oscillations in the decay traces with a period of ~1 ps, consistent with a vibrational coherence and relaxation from a higher upsilon(N-H) vibrational level or levels on the timescale for back EPT. PMID- 27660241 TI - The Neural Code for Pain: From Single-Cell Electrophysiology to the Dynamic Pain Connectome. AB - Pain occurs in time. In naturalistic settings, pain perception is sometimes stable but often varies in intensity and quality over the course of seconds, minutes, and days. A principal aim in classic electrophysiology studies of pain was to uncover a neural code based on the temporal patterns of single neuron firing. In contrast, modern neuroimaging studies have placed emphasis on uncovering the spatial pattern of brain activity (or "map") that may reflect the pain experience. However, in the emerging field of connectomics, communication within and among brain networks is characterized as intrinsically dynamic on multiple time scales. In this review, we revisit the single-cell electrophysiological evidence for a nociceptive neural code and consider how those findings relate to recent advances in understanding systems-level dynamic processes that suggest the existence of a "dynamic pain connectome" as a spatiotemporal physiological signature of pain. We explore how spontaneous activity fluctuations in this dynamic system shape, and are shaped by, acute and chronic pain experiences and individual differences in those experiences. Highlighting the temporal dimension of pain, we aim to move pain theory beyond the concept of a static neurosignature and toward an ethologically relevant account of naturalistic dynamics. PMID- 27660243 TI - World leaders pledge action on antimicrobial resistance. PMID- 27660242 TI - Tissue transglutaminase-1 promotes stemness and chemoresistance in gastric cancer cells by regulating Wnt/beta-catenin signaling. AB - Gastric cancer is a common malignancy, and is one of the most frequent causes of cancer deaths worldwide. Recently, members of the transglutaminases (TGM) family, especially TGM2, have been implicated in the progression and drug resistance of cancers, but the function of TGM1 in cancer development has been largely overlooked. In this study, we demonstrate the roles of TGM1 in development of gastric cancer. We found that expression levels of TGM1 were upregulated in both gastric cancer tissues and cultured gastric cancer cells, and that TGM1 expression levels were correlated with patient survival. In cultured gastric cancer cells, loss of TGM1 expression inhibited cell proliferation and promoted apoptosis, as well increased gastric cancer cell sensitivity to chemotherapeutic drugs and reducing stemness. These results strongly supported the participation of TGM1 in the regulation of gastric cancer development. In addition, we found evidence that the mechanism of action of TGM1 in regulating gastric cancer cell might involve the Wnt signaling pathway, as loss of TGM1 expression in gastric cancer cells led to a significant suppression of Wnt signaling activities. PMID- 27660244 TI - Constitutive Desensitization of Opioid Receptors in Peripheral Sensory Neurons. AB - Opioid receptors expressed by peripheral pain-sensing neurons are functionally inactive for antinociceptive signaling under most basal conditions; however, tissue damage or exposure to inflammatory mediators (e.g., bradykinin) converts these receptors from a nonresponsive state to a functionally competent state. Here we tested the hypothesis that the basal, nonresponsive state of the mu- and delta-opioid receptors (MOR and DOR, respectively) is the result of constitutive receptor activity that activates desensitization mechanisms, resulting in MOR and DOR receptor systems that are constitutively desensitized. Consistent with our previous findings, under basal conditions, neither the MOR agonist [d-Ala2,N MePhe4,Gly-ol5]-enkephalin nor the DOR agonist [d-Pen2,5]-enkephalin, inhibited prostaglandin E2 (PGE2)-stimulated cAMP accumulation in peripheral sensory neurons in culture (ex vivo) or inhibited PGE2-stimulated thermal allodynia in the rat hind paw in vivo. Prolonged treatment with naloxone induced MOR and DOR responsiveness both in vivo and ex vivo to a similar magnitude as that produced by bradykinin. Also similar to bradykinin, the effect of naloxone persisted for 60 minutes after washout of the ligand. By contrast, prolonged treatment with 6beta-naltrexol, did not induce functional competence of MOR or DOR but blocked the effect of naloxone. Treatment with siRNA for beta-arrestin-2, but not beta arrestin-1, also induced MOR and DOR functional competence in cultured peripheral sensory neurons. These data suggest that the lack of responsiveness of MOR and DOR to agonist for antinociceptive signaling in peripheral sensory neurons is due to constitutive desensitization that is likely mediated by beta-arrestin-2. PMID- 27660245 TI - Mortality after esophagectomy is heavily impacted by center volume: retrospective analysis of the Nationwide Inpatient Sample. AB - BACKGROUND: The effects of hospital volume on in-hospital mortality after esophageal resection are disputed in the literature. We sought to analyze treatment effects in patient subpopulations that undergo esophagectomy for cancer based on hospital volume. METHODS: We performed a retrospective analysis of the Nationwide Inpatient Sample from 1998 to 2011. Patients who underwent open or laparoscopic transhiatal and transthoracic esophageal resection were identified using ICD-9 codes. Patients <18 years and those with peritoneal disease were excluded. Multivariate logistic regression analyses were used with mortality as the independent variable to evaluate the effect of low (<6), intermediate (6-19), and high (>=20) hospital volume of esophagectomies. These analyses were repeated in different subsets of patients to determine whether hospital volume affected mortality depending on the subpopulation evaluated. Subgroups were created depending on age, race, gender, operative approach, comorbidities, and tumor pathology. RESULTS: A total of 23,751 patients were included. The overall perioperative mortality rate was 7.7 % (low volume: 11.4 %; intermediate volume: 8.39 %, high volume: 4.01 %), and multivariate analysis revealed that high hospital volume had a protective effect (OR 0.54, 95 % CI 0.45-0.65). On subgroup analyses for low- and intermediate-volume hospitals, mortality was uniformly elevated for the subpopulations when comparing to high-volume hospitals (p < 0.05). There was no difference in mortality between low- and medium-volume hospitals and between subgroups. CONCLUSION: No lower mortality risk subgroup could be identified in this nationwide collective. This analysis emphasizes that perioperative mortality after esophagectomy for cancer is lower in high-volume hospitals. PMID- 27660246 TI - A magnetic levitation robotic camera for minimally invasive surgery: Useful for NOTES? AB - BACKGROUND: Minimally invasive surgery (MIS) is rising in popularity generating a revolution in operative medicine during the past few decades. Although laparoscopic techniques have not significantly changed in the last 10 years, several advances have been made in visualization devices and instrumentation. METHODS: Our team, composed of surgeons and biomedical engineers, developed a magnetic levitation camera (MLC) with a magnetic internal mechanism dedicated to MIS. Three animal trials were performed. Porcine acute model has been chosen after animal ethical committee approval, and laparoscopic cholecystectomy, nephrectomy and hernioplastic repair have been performed. RESULTS: MLC permits to complete efficiently several two-port laparoscopy surgeries reducing patients' invasiveness and at the same time saving surgeon's dexterity. CONCLUSIONS: We strongly believe that insertable and softly tethered devices like MLS camera will be an integral part of future surgical systems, thus improving procedures efficiency, minimizing invasiveness and enhancing surgeon dexterity and versatility of visions angles. PMID- 27660248 TI - Distraction osteogenesis for tibial nonunion with bone loss using combined Ilizarov and Taylor spatial frames versus a conventional circular frame. AB - This retrospective review assesses 55 tibial nonunions with bone loss to compare union achieved with combined Ilizarov and Taylor spatial frames (I-TSF) versus a conventional circular frame with the standard Ilizarov procedure. Seventeen (31 %) of the 55 nonunions were infected. Thirty patients treated with I-TSF were compared with 25 patients treated with a conventional circular frame. In the I TSF group, an average of 7.6 cm of bone was resected and the lengthening index (treatment time in months divided by lengthening amount in centimeters) was 1.97. In the conventional circular frame group, a mean of 6.5 cm was resected and the lengthening index was 2.1. Consolidation at the docking site and at the regenerate bone occurred in 49 (89 %) of 55 cases after the first procedure. No statistically significant difference was shown between the two groups. Superiority of one modality of treatment over the other cannot be concluded from our data. Application of combined Ilizarov and Taylor spatial frames for bone transport is useful for treatment of tibial nonunion with bone loss. Level of evidence Case series, Level III. PMID- 27660250 TI - Erratum to: Brodalumab: First Global Approval. PMID- 27660251 TI - Socioeconomic status as a factor in Indigenous and non-Indigenous children with hearing loss: analysis of national survey data. AB - In this paper, the association between socioeconomic status and speech, language and communication outcomes for primary-school-going children with hearing loss using population survey data was analysed. The dataset used for analysis consisted of 289973 children in total, of which 3174 children had hearing loss. For all children, higher socioeconomic status was positively correlated with better speech, language and communication outcomes. A hearing loss was indicated for 1% of non-Indigenous children and 4.3% of Indigenous children. Non-Indigenous children with hearing loss were found to be fairly evenly distributed by socioeconomic status, whereas Indigenous children with hearing loss were found to be statistically significantly more likely to be living in the most disadvantaged socioeconomic areas. Socioeconomic status was found to affect developmental outcomes for all children, regardless of Indigenous and hearing loss status. PMID- 27660249 TI - Identifying the risk factors causing iatrogenic mandibular fractures associated with exodontia: a systemic meta-analysis of 200 cases from 1953 to 2015. AB - PURPOSE: Iatrogenic fracture of mandible (IFM) associated with exodontia though rare, they do occur with an incidence ranging from 0.0034 to 0.0075 %. Most of the data is in the form of case reports or a small case series. This is an attempt to amass the data available in literature since the last 62 years. The purpose of this meta-analysis is to identify the etiologies and risk factors leading to IFM associated with exodontia and also the measures to minimize the complication. METHODS: Articles published between 1953 and 2015 were searched in Medline database. Data was collected and analyzed based on age, gender, extracted tooth, status of dentition, pathological bone lesion adjacent to the tooth, type of impaction, angulation of the impacted third molar, site of fracture, side of fracture, time of fracture, and treatment of fracture. RESULTS: A review identified 200 documented cases of IFM associated with the removal of teeth. The reasons for its occurrence found to be multifactorial with a higher incidence in the fifth decade of life with male prevalence. Risk factors more commonly identified were removal of the third molar, fully dentate patient, associated pathology, impacted tooth, angle region, left quadrant, and time interval of 3 weeks postoperatively. CONCLUSIONS: IFM related to the removal of teeth is a rare complication. Identifying and addressing the risk factors will enable the surgeon to avoid the complication of IFM associated with exodontia. PMID- 27660253 TI - High frequency oscillatory ventilation for adult ARDS: Is this the end of the road? PMID- 27660252 TI - Sepsis and septic shock-is a microcirculation a main player? AB - Shock, defined at a cellular level, is a condition in which oxygen delivery to the cells is not sufficient to sustain cellular activity and support organ function. The central role of microcirculation in providing oxygen to the cells makes it of prime importance in determining organ function. In sepsis and septic shock, macrocirculatory alterations and microcirculatory dysfunction participate concurrently in the pathophysiology of organ failure. Haemodynamic coherence in shock is a condition in which normalization of systemic haemodynamic variables results in simultaneous amelioration in the perfusion of the microcirculation and restoration of tissue oxygenation as a final result. Septic shock is most frequently characterized by a lack of microcirculatory recruitment despite of macrocirculatory successful resuscitation. The lack of haemodynamic coherence between macrocirculation and microcirculation in septic patients results in treatment failure and increased mortality. The monitoring of microcirculation and the effects of its changes are an important area of future clinical research and treatment modification. PMID- 27660247 TI - Diagnosis and management of acute appendicitis. EAES consensus development conference 2015. AB - Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis. PMID- 27660255 TI - Aneuploid progenies of triploid hybrids between diploid and tetraploid loach Misgurnus anguillicaudatus in China. AB - Triploid Chinese loach, Misgurnus anguillicaudatus, hybrids between tetraploids from Hubei Province and diploids from Liaoning Province were mated with either diploid wild-type or triploid hybrids to analyze viability and ploidy of the resultant progenies. Both triploid males and females generated fertile gametes, but progenies from the crosses using gametes of triploid hybrids did not survive beyond the larval stages. In crosses between wild-type diploid females and triploid hybrid males, embryos ranging from 2.2n to 2.6n were predominant with a mode of either 2.4n (chromosome numbers 59, 60, 61) or 2.5n (chromosome numbers 62, 63). Those from the crosses between triploid hybrid females and diploid males gave a modal ploidy level at approximately 2.5n in one case, but a shift to a higher ploidy level was observed in other embryos. In the progenies between triploid hybrid females and males, the ploidy level at approximately 3.0n (chromosome numbers 74, 75, 76) was most frequent. The cytogenetic results of the progenies suggest the production of aneuploid gametes with a modal ploidy level at approximately 1.5n in triploid hybrids. However, a shift to higher chromosome numbers in gametes was observed in certain cases, suggesting the involvement of mortality selection of gametes and/or zygotes with lower chromosome numbers. PMID- 27660254 TI - Chromosome mapping of repetitive DNAs in sergeant major fishes (Abudefdufinae, Pomacentridae): a general view on the chromosomal conservatism of the genus. AB - Species of the Abudefduf genus (sergeant-majors) are widely distributed in the Indian, Pacific and Atlantic oceans, with large schools inhabiting rocky coastal regions and coral reefs. This genus consists of twenty recognized species are of generalist habit, showing typical characteristics of colonizers. Some populations maintain gene flow between large oceanic areas, a condition that may influence their cytogenetic features. A number of species have been shown to be invaders and able to hybridize with local species. However, cytogenetic data in this genus are restricted to few species. In this way, the present study includes the chromosomal investigation, using conventional (Giemsa staining, Ag-NOR and C banding) and molecular (in situ mapping of six different repetitive DNA classes) approaches in four Abudefduf species from different oceanic regions (A. bengalensis and A. sexfasciatus from the Indo-Pacific, A. vaigiensis from the Indian and A. saxatilis from the Atlantic oceans, respectively), to investigate the evolutionary events associated with the chromosomal diversification in this group. All species share a similar karyotype (2n = 48; NF = 52), except A. sexfasciatus (2n = 48; NF = 50), which possesses a characteristic pericentric inversion in the NOR-bearing chromosomal pair. Mapping of repetitive sequences suggests a chromosomal conservatism in this genus. The high karyotypic similarity between allopatric species of Abudefduf may be related to the success of natural viable hybrids among species with recent secondary contact. PMID- 27660256 TI - Imaging for Quality Control: Comparison of Systematic Video Recording to the Operative Note in Colorectal Cancer Surgery. A Pilot Study. AB - BACKGROUND: Oncological and functional results after colorectal cancer surgery vary considerably between hospitals and surgeons. At present, the only source of technical information about the surgical procedure is the operative note, which is subjective and omits critical information. This study aimed to evaluate the feasibility of operative video recording in demonstrating both objective information concerning the surgical procedure and surgical quality, as using a systematic approach might improve surgical performance. METHODS: From July 2015 through November 2015, patients aged >=18 years undergoing elective colorectal cancer surgery were prospectively included in a single-institution trial. Video recording of key moments was performed peroperatively and analyzed for adequacy. The study cases were compared with a historic cohort. Video was compared with the operative note using the amount of adequate steps and a scoring system. RESULTS: This study compared 15 cases to 32 cases from the historic control group. Compared to the written operative note alone, significant differences in availability of information were seen in favor of video as well as using a combination of video plus the operative note (N adequate steps p = .024; p = <.001. Adequacy score: p = .039; p = <.001, both respectively). CONCLUSIONS: Systematic video registration is feasible and seems to improve the availability of essential information after colorectal cancer surgery. In this respect, combining video with a traditional operative note would be the best option. A multicenter international study is being organized to further evaluate the effect of operative video capture on surgical outcomes. PMID- 27660257 TI - The Preoperative Neutrophil-to-lymphocyte Ratio is a Novel Biomarker for Predicting Worse Clinical Outcomes in Non-muscle Invasive Bladder Cancer Patients with a Previous History of Smoking. AB - PURPOSE: We speculated that a heterogeneous population of non-muscle invasive bladder cancer (NMIBC) patients with a previous history of smoking may be more precisely stratified by a biomarker associated with tumor aggressiveness and then focused on the preoperative neutrophil-to-lymphocyte ratio (pre-NLR), which is a simple index of systemic inflammation. METHODS: Our study population comprised 605 patients initially diagnosed with NMIBC at our 3 institutions between 1995 and 2013. We analyzed the relationships between pre-NLR levels and clinical outcomes in NMIBC. A pre-NLR level of >=2.2 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: In overall, a total of 296 patients (48.9 %) had pre-NLR >= 2.2, and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. Among 344 patients with a previous history of smoking, 184 (53.5 %) had pre-NLR >= 2.2 and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. The 5-year recurrence-free survival and progression-free survival rates in patients with pre-NLR < 2.2 were 66.3 and 97.5 %, respectively, which were significantly higher than those in their counterparts (31.7 and 90.4 %, p < 0.001). In either subgroup of patients who were current smokers (N = 175) or former smokers (N = 169), the pre-NLR level was the only independent risk factor for tumor recurrence. The pre-NLR level was not associated with tumor recurrence or stage progression in 261 nonsmoking patients. CONCLUSIONS: Pre-NLR levels may be a useful marker for identifying worse clinical outcomes in NMIBC patients, particularly those with a previous history of smoking. PMID- 27660258 TI - Low-grade Appendiceal Mucinous Neoplasm of Uncertain Malignant Potential (LAMN UMP): Prognostic Factors and Implications for Treatment and Follow-up. AB - BACKGROUND: Low-grade appendiceal mucinous neoplasm of uncertain malignant potential are poorly understood lesions characterized by extraluminal mucin or fibrosis with neoplastic cells confined to the appendiceal lumen. The purpose of this study is to investigate the clinical and pathologic parameters of these lesions to optimize our understanding and management of these tumors. METHODS: Subjects with these tumors were identified from the appendiceal tumor databases at the University of Texas MD Anderson Cancer Center. Univariate and multivariate Cox proportional hazards regression analyses assessed relationships between clinicopathologic variables [including age, gender, margin status and serum levels of the tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA) 125, and CA19-9] disease-free survival, postrecurrence survival and overall survival. RESULTS: Ninety-eight subjects with this disease were identified. Most patients did not experience disease recurrence after initial appendectomy. At last follow-up, 25 (26 %) had disease recurrence or died. Of the 20 patients who had disease recurrence, 5 (25 %) died, and 15 (75 %) were alive. Disease-free survival was significantly reduced with positive margin status (p = 0.02) and elevated serum levels of CEA (p < 0.001), CA19-9 (p = 0.01), or CA-125 (p = 0.002) at the time of appendectomy. The median postrecurrence survival time was 4.7 years and the 5-year postrecurrence survival rate was 41 % (standard error = 18 %). CONCLUSIONS: Patients with Low-grade appendiceal mucinous neoplasm of uncertain malignant potential who have negative margins and normal tumor marker levels have a lower risk for recurrence. In these patients, expectant management is sufficient. Elevated tumor marker levels at the time of appendectomy marks an increased risk of recurrence or death and signals the need for closer monitoring or intervention. PMID- 27660260 TI - 40 years of veterinary papers in JAC - what have we learnt? AB - This review, for the occasion of the 40th anniversary of the Journal of Antimicrobial Chemotherapy (JAC), gives an overview of the manuscripts related to veterinary bacteriology published in the journal in the past 40 years with a focus on 'One Health' aspects. From 1975 to 2000 the number of manuscripts related to veterinary medicine was limited, but thereafter, the number steadily increased. Most manuscripts published were related to food-producing animals, but companion animals and minor species were also covered. Subjects included antimicrobial usage in animals and the consequences for human medicine, new resistance genes and mechanisms, the prevalence and epidemiology of antimicrobial resistance, and the emergence of resistant bacteria in animals with zoonotic potential such as livestock-associated MRSA (LA-MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP) and ESBL-producing Enterobacteriaceae. These manuscripts have added to our knowledge on the risks of transmission of resistant bacteria from animals to humans and the importance of the prudent use of antimicrobial agents in veterinary medicine. PMID- 27660259 TI - Comparison of Single-Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) and Conventional Planar Lymphoscintigraphy for Sentinel Node Localization in Patients with Cutaneous Malignancies. AB - BACKGROUND: Accurate preoperative lymphoscintigraphy is vital to performing sentinel lymph node biopsy (SLNB) for cutaneous malignancies. Potential advantages of single-photon emission computed tomography with integrated computed tomography (SPECT/CT) include the ability to readily identify aberrant drainage patterns as well as provide the surgeon with three-dimensional anatomic landmarks not seen on conventional planar lymphoscintigraphy (PLS). METHODS: Patients with cutaneous malignancies who underwent SLNB with preoperative imaging using both SPECT/CT and PLS from 2011 to 2014 were identified. RESULTS: Both SPECT/CT and PLS were obtained in 351 patients (median age, 69 years; range, 5-94 years) with cutaneous malignancies (melanoma = 300, Merkel cell carcinoma = 33, squamous cell carcinoma = 8, other = 10) after intradermal injection of 99mtechnetium sulfur colloid (median dose 300 uCi). A mean of 4.3 hot spots were identified on SPECT/CT compared to 3.0 on PLS (p < 0.001). One hundred fifty-three patients (43.6 %) had identical findings between SPECT/CT and PLS, while 172 (49 %) had additional hot spots identified on SPECT/CT compared to only 24 (6.8 %) additional on PLS. SPECT/CT demonstrated additional nodal basins in 103 patients (29.4 %), compared to only 11 patients (3.1 %) with additional basins on PLS. CONCLUSIONS: SPECT/CT is a useful adjunct that can help with sentinel node localization in challenging cases. It identified additional hot spots not seen on PLS in almost 50 % of patients. Because PLS identified hot spots not seen on SPECT/CT in 6.8 % of patients, we recommend using both modalities jointly. Long term follow-up will be required to validate the clinical significance of the additional hot spots identified by SPECT/CT. PMID- 27660261 TI - Asymptotic Robustness Study of the Polychoric Correlation Estimation. AB - Asymptotic robustness against misspecification of the underlying distribution for the polychoric correlation estimation is studied. The asymptotic normality of the pseudo-maximum likelihood estimator is derived using the two-step estimation procedure. The t distribution assumption and the skew-normal distribution assumption are used as alternatives to the normal distribution assumption in a numerical study. The numerical results show that the underlying normal distribution can be substantially biased, even though skewness and kurtosis are not large. The skew-normal assumption generally produces a lower bias than the normal assumption. Thus, it is worth using a non-normal distributional assumption if the normal assumption is dubious. PMID- 27660262 TI - Serum Markers of Neurodegeneration in Maple Syrup Urine Disease. AB - Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain alpha-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective alpha-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD. PMID- 27660264 TI - Cholinergic Oculomotor Nucleus Activity Is Induced by REM Sleep Deprivation Negatively Impacting on Cognition. AB - Several efforts have been made to understand the involvement of rapid eye movement (REM) sleep for cognitive processes. Consolidation or retention of recognition memories is severely disrupted by REM sleep deprivation (REMSD). In this regard, pedunculopontine tegmental nucleus (PPT) and other brainstem nuclei, such as pontine nucleus (Pn) and oculomotor nucleus (OCM), appear to be candidates to take part in this REM sleep circuitry with potential involvement in cognition. Therefore, the objective of this study was to investigate a possible association between the performance of Wistar rats in a declarative memory and PPT, Pn, and OCM activities after different periods of REMSD. We examined c-Fos and choline acetyltransferase (ChaT) expressions as indicators of neuronal activity as well as a familiarity-based memory test. The animals were distributed in groups: control, REMSD, and sleep rebound (REB). At the end of the different REMSD (24, 48, 72, and 96 h) and REB (24 h) time points, the rats were immediately tested in the object recognition test and then the brains were collected. Results indicated that OCM neurons presented an increased activity, due to ChaT-labeling associated with REMSD that negatively correlated (r = -0.32) with the cognitive performance. This suggests the existence of a cholinergic compensatory mechanism within the OCM during REMSD. We also showed that 24 h of REMSD impacted similarly in memory, compared to longer periods of REMSD. These data extend the notion that REM sleep is influenced by areas other than PPT, i.e., Pn and OCM, which could be key players in both sleep processes and cognition. PMID- 27660263 TI - MicroRNA-Mediated Reprogramming of Somatic Cells into Neural Stem Cells or Neurons. AB - Cellular reprogramming is a promising strategy to generate neural stem cells (NSCs) or desired subtype-specific neurons for cell-based therapeutic intervention. By far, the intricate cell event like reprogramming of non-neural cells to desired cell types can be achieved by forced expression of lineage related transcription factors (TFs), nuclear transfer, a defined set of factors, and via non-coding microRNAs (miRNAs), as well as other precisely defined conditions. In addition, scientists have been trying to develop better approaches for reprogramming, either by using distinct combinations of a set of small molecules and certain TFs or delivery of appropriate small molecules and miRNAs. The miRNA-mediated approach is fascinating because of its potential to rapidly generate a variety of therapeutically desired cell types from other cell lineages. Recent studies have made great progress in miRNA-mediated neural reprogramming of somatic cells to various specific neuronal subtypes with more efficiency even though the exact mechanisms remain to be further explored. Based on key roles of miRNAs in neural reprogramming across differentiated cell lineages, it is of vital interest to summarize the recent knowledge regarding the instructive role of miRNAs in direct conversion of somatic cells into neural lineages. This precise review mainly focuses on recent discoveries of miRNAs functions in initiating cell reprogramming and fate specification of the neuronal subtype. Moreover, we discuss most recent findings about some miRNAs' activity in regulating various developmental stages of neurons, which is helpful for understanding the event network between miRNAs and their targets. PMID- 27660265 TI - Reciprocal MicroRNA Expression in Mesocortical Circuit and Its Interplay with Serotonin Transporter Define Resilient Rats in the Chronic Mild Stress. AB - Prolonged stress perturbs physiological balance of a subject and thus can lead to depression. Nevertheless, some individuals are more resilient to stress than the others. Defining molecular factors underlying resilience to stress may contribute to the development of a new antidepressant strategy based on the restoration of resilient phenotype in depressed subjects. We used chronic mild stress (CMS) paradigm-well-characterized animal model of depression which caused in rats behavioral deficits (anhedonia) manifested by decreased consumption of sucrose solution. CMS also generated a proportion of resilient rats which did not alter sucrose consumption despite being stressed. Recently, regulation of a gene expression associated with microRNA (miRNA) is considered as an important factor modulating biochemical response to stress. Based on our previous work and literature survey, we investigated changes in the expression level of seven miRNAs (i.e., miR-18a-5p, miR-34a-5p, miR-135a-5p, miR-195-5p, miR-320-3p, miR 674-3p, miR-872-5p) in mesocortical circuit-crucially involved in stress response in order to find differences between susceptible and resilient phenotype. Bioinformatic analysis showed that all miRNAs of interest potentially target serotonin transporter (SERT). Chronic stress caused global increase in the expression of the abovementioned miRNAs in ventral tegmental area (VTA) of stressed rats followed by parallel decrease in miRNA expression in prefrontal cortex (PCx). This effect was more profound in resilient than anhedonic animals. Moreover, we observed decreased level of SERT in VTA of resilient rats. Our findings show that mesocortical circuit is involved in the response to stress and this phenomenon is more efficient in resilient animals. PMID- 27660266 TI - Neurotoxicity of Methylmercury in Isolated Astrocytes and Neurons: the Cytoskeleton as a Main Target. AB - In the present work, we focused on mechanisms of methylmercury (MeHg) toxicity in primary astrocytes and neurons of rats. Cortical astrocytes and neurons exposed to 0.5-5 MUM MeHg present a link among morphological alterations, glutathione (GSH) depletion, glutamate dyshomeostasis, and cell death. Disrupted neuronal cytoskeleton was assessed by decreased neurite length and neurite/neuron ratio. Astrocytes presented reorganization of actin and glial fibrillary acidic protein (GFAP) networks and reduced cytoplasmic area. Glutamate uptake and Na+K+ATPase activity in MeHg-treated astrocytes were preserved; however, downregulated EAAC1 mediated glutamate uptake was associated with impaired Na+K+ATPase activity in neurons. Oxidative imbalance was found in astrocytes and neurons through increased 2'7'-dichlorofluorescein (DCF) production and misregulated superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GPX) activities. Glutathione (GSH) levels were downregulated in both astrocytes and neurons. MeHg reduced neuronal viability and induced caspase 3-dependent apoptosis together with downregulated PI3K/Akt pathway. In astrocytes, necrotic death was associated with increased TNF-alpha and JNK/MAPK activities. Cytoskeletal remodeling and cell death were fully prevented in astrocytes and neurons by GSH, but not melatonin or Trolox supplementation. These findings support a role for depleted GSH in the cytotoxicity of MeHg leading to disruption of the cytoskeleton and cell death. Moreover, in neurons, glutamate antagonists also prevented cytoskeletal disruption and neuronal death. We propose that cytoskeleton is an end point in MeHg cytotoxicity. Oxidative imbalance and glutamate mechanisms mediate MeHg cytoskeletal disruption and apoptosis in neurons. Otherwise, redox imbalance and glutamate-independent mechanisms disrupted the cytoskeleton and induced necrosis in MeHg-exposed astrocyte. PMID- 27660267 TI - Activation of Transient Receptor Potential Vanilloid 4 Promotes the Proliferation of Stem Cells in the Adult Hippocampal Dentate Gyrus. AB - Neurogenesis plays an important role in adult hippocampal function, and this process can be modulated by intracellular calcium. The activation of transient receptor potential vanilloid 4 (TRPV4) induces an increase in intracellular calcium concentration, but whether neurogenesis can be modulated by TRPV4 activation remains unclear. Here, we report that intracerebroventricular injection of the TRPV4 agonist GSK1016790A for 5 days enhanced the proliferation of stem cells in the hippocampal dentate gyrus (DG) of adult mice without affecting neurite growth, differentiation, or survival of newborn cells. GSK1016790A induced increases in the hippocampal protein levels of cyclin dependent kinase (CDK) 6, CDK2, cyclin E1, and cyclin A2 but did not affect CDK4 and cyclin D1 expression. The phosphorylation of retinoblastoma protein (Rb) in hippocampi was enhanced in GSK1016790A-injected mice compared with control mice. Moreover, hippocampal protein levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were enhanced by GSK1016790A. Finally, GSK1016790A-enhanced proliferation was markedly blocked by a MAPK/ERK kinase or p38 MAPK antagonist (U0126 or SB203580, respectively). The increased protein levels of CDK2 and CDK6, as well as those of cyclin E1 and cyclin A2, in GSK1016790A-injected mice were substantially reduced by co-injection of U0126 or SB203580. We conclude that TRPV4 activation results in the proliferation of stem cells in the adult hippocampal DG, which is likely mediated through ERK1/2 and p38 MAPK signaling to increase the expression of CDKs (CDK6 and CDK2) and cyclins (cyclin E1 and A2), phosphorylate Rb consequently, and accelerate the cell cycle ultimately. PMID- 27660270 TI - Hyperpalatable Diet and Physical Exercise Modulate the Expression of the Glial Monocarboxylate Transporters MCT1 and 4. AB - Hyperpalatable diets (HP) impair brain metabolism, and regular physical exercise has an apparent opposite effect. Here, we combined a prior long-term exposure to HP diet followed by physical exercise and evaluated the impact on some neuroenergetic components and on cognitive performance. We assessed the extracellular lactate concentration, expression of monocarboxylate transporters (MCTs), pyruvate dehydrogenase (PDH), and mitochondrial function in the hippocampus. Male C57BL/6J mice were fed 4 months with HP or a control diet. Subsequently, they were divided in the following groups: control diet sedentary (CDS), control diet exercise (CDE), HP diet sedentary (HPS), and HP diet exercise (HPE) (n = 15 per group) and were engaged for an additional 30-day period of voluntary exercise and HP diet. Relative to the control situation, exercise increased MCT1, MCT4, and PDH protein levels, while the HP diet increased MCT1 and MCT4 protein levels. The production of hydrogen peroxide (H2O2) and the mitochondrial membrane potential (??m) stimulated by succinate in hippocampal homogenates were not significantly different between groups. ADP phosphorylation and the maximal respiratory rate induced by FCCP showed similar responses between groups, implying a normal mitochondrial function. Also, extracellular brain lactate levels were increased in the HPE group compared to other groups soon after performing the Y-maze task. However, such enhanced lactate levels were not associated with improved memory performance. In summary, hippocampal protein expression levels of MCT1 and 4 were increased by physical exercise and HP diet, whereas PDH was only increased by exercise. These observations indicate that a hippocampal metabolic reprogramming takes place in response to these environmental factors. PMID- 27660269 TI - ER Stress Induced by Tunicamycin Triggers alpha-Synuclein Oligomerization, Dopaminergic Neurons Death and Locomotor Impairment: a New Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD's etiology is unknown, alpha-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction. Increasing experimental evidence indicates that ER stress is involved in PD, however most of the described results employed cultured cell lines and genetically modified animal models. In this study, we developed a new ER stress rat model employing the well known ER stressor tunicamycin (Tm). To evaluate if ER stress was able to induce PD features, we performed an intranigral injection of Tm (0.1 MUg/cerebral hemisphere) and animals (male Wistar rats) were analyzed 7 days post injection. The classical 6-OHDA neurotoxin model (1 MUg/cerebral hemisphere) was used as an established positive control for PD. We show that Tm injection induced locomotor impairment, dopaminergic neurons death, and activation of astroglia. In addition, we observed an extensive alpha-synuclein oligomerization in SNpc of Tm-injected animals when compared with DMSO-injected controls. Finally, both Tm and 6-OHDA treated animals presented increased levels of ER stress markers. Taken together, these findings show for the first time that the ER stressor Tm recapitulates some of the phenotypic characteristics observed in rodent models of PD, reinforcing the concept that ER stress could be an important contributor to the pathophysiology of PD. Therefore, we propose the intranigral Tm injection as a new ER stress-based model for the study of PD in vivo. PMID- 27660271 TI - Neuroprotection Through Rapamycin-Induced Activation of Autophagy and PI3K/Akt1/mTOR/CREB Signaling Against Amyloid-beta-Induced Oxidative Stress, Synaptic/Neurotransmission Dysfunction, and Neurodegeneration in Adult Rats. AB - Autophagy is a catabolic process involved in the continuous removal of toxic protein aggregates and cellular organelles to maintain the homeostasis and functional integrity of cells. The mechanistic understanding of autophagy mediated neuroprotection during the development of neurodegenerative disorders remains elusive. Here, we investigated the potential role of rapamycin-induced activation of autophagy and PI3K/Akt1/mTOR/CREB pathway(s) in the neuroprotection of amyloid-beta (Abeta1-42)-insulted hippocampal neurons in rat model of Alzheimer's disease (AD) like phenotypes. A single intra-hippocampal injection of Abeta1-42 impaired redox balance and markedly induced synaptic dysfunction, neurotransmission dysfunction, and cognitive deficit, and suppressed pro-survival signaling in the adult rats. Rapamycin administration caused a significant reduction of mTOR complex 1 phosphorylation at Ser2481 and a significant increase in levels of autophagy markers such as microtubule-associated protein-1 light chain-3 (LC3), beclin-1, sequestosome-1/p62, unc-51-like kinase 1 (ULK1). In addition, rapamycin induced the activation of autophagy that further activated p PI3K, p-Akt1 (Ser473), and p-CREB (Ser183) expression in Abeta1-42-treated rats. The activated autophagy markedly reversed Abeta1-42-induced impaired redox homeostasis by decreasing the levels of prooxidants-ROS generation, intracellular Ca2+ flux and LPO, and increasing the levels of antioxidants-SOD, catalase, and GSH. The activated autophagy also provided significant neuroprotection against Abeta1-42-induced synaptic dysfunction by increasing the expression of synapsin I, synaptophysin, and PSD95; and neurotransmission dysfunction by increasing the levels of CHRM2, DAD2 receptor, NMDA receptor, and AMPA receptor; and ultimately improved cognitive ability in rats. Wortmannin administration significantly reduced the expression of autophagy markers, p-PI3K, p-Akt1, and p-CREB, as well as the autophagy mediated neuroprotective effect. Our study demonstrate that autophagy can be an integrated part of pro-survival (PI3K/Akt1/mTOR/CREB) signaling and autophagic activation restores the oxidative defense mechanism(s), neurodegenerative damages, and maintains the integrity of synapse and neurotransmission in rat model of AD. PMID- 27660268 TI - Role of STAT3 in Genesis and Progression of Human Malignant Gliomas. AB - Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in glioblastoma and has been identified as a relevant therapeutic target in this disease and many other human cancers. After two decades of intensive research, there is not yet any approved STAT3-based glioma therapy. In addition to the canonical activation by tyrosine 705 phosphorylation, concordant reports described a potential therapeutic relevance of other post-translational modifications including mainly serine 727 phosphorylation. Such reports reinforce the need to refine the strategy of targeting STAT3 in each concerned disease. This review focuses on the role of serine 727 and tyrosine 705 phosphorylation of STAT3 in glioma. It explores their contribution to glial cell transformation and to the mechanisms that make glioma escape to both immune control and standard treatment. PMID- 27660275 TI - Associations of Serum Cytokine Receptor Levels with Melancholia, Staging of Illness, Depressive and Manic Phases, and Severity of Depression in Bipolar Disorder. AB - To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80 kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski's stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers. PMID- 27660274 TI - A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen. AB - Convergent evidence from genetics, symptomatology, and psychopharmacology implies that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD); for example, any two or even three of these disorders could co-exist in some families. A total of 48,753 single nucleotide polymorphisms (SNPs) on chromosome 8 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type I), 177 MDD patients, and 1000 controls. Associated SNP loci were comprehensively revealed, and outstanding susceptibility genes were identified including CSMD1, NRG1, PXDNL, SGCZ, and TMEM66. Unexpectedly, flanking genes for up to 95.9 % of the associated SNPs were replicated (P <= 9.9E-8) in the enlarged cohort of 986 SCZ patients. Considering convergent evidence, our results implicate that bipolar disorder and major depressive disorder might be subtypes of schizophrenia. PMID- 27660272 TI - Modulation of Molecular Chaperones in Huntington's Disease and Other Polyglutamine Disorders. AB - Polyglutamine expansion mutations in specific proteins underlie the pathogenesis of a group of progressive neurodegenerative disorders, including Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and several spinocerebellar ataxias. The different mutant proteins share ubiquitous expression and abnormal proteostasis, with misfolding and aggregation, but nevertheless evoke distinct patterns of neurodegeneration. This highlights the relevance of the full protein context where the polyglutamine expansion occurs and suggests different interactions with the cellular proteostasis machinery. Molecular chaperones are key elements of the proteostasis machinery and therapeutic targets for neurodegeneration. Here, we provide a focused review on Hsp90, Hsp70, and their co-chaperones, and how their genetic or pharmacological modulation affects the proteostasis and disease phenotypes in cellular and animal models of polyglutamine disorders. The emerging picture is that, in principle, Hsp70 modulation may be more amenable for long-term treatment by promoting a more selective clearance of mutant proteins than Hsp90 modulation, which may further decrease the necessary wild-type counterparts. It seems, nevertheless, unlikely that a single Hsp70 modulator will benefit all polyglutamine diseases. Indeed, available data, together with insights from effects on tau and alpha-synuclein in models of Alzheimer's and Parkinson's diseases, indicates that Hsp70 modulators may lead to different effects on the proteostasis of different mutant and wild-type client proteins. Future studies should include the further development of isoform selective inhibitors, namely to avoid off-target effects on Hsp in the mitochondria, and their characterization in distinct polyglutamine disease models to account for client protein-specific differences. PMID- 27660273 TI - Role of Autophagy in HIV Pathogenesis and Drug Abuse. AB - Autophagy is a highly regulated process in which excessive cytoplasmic materials are captured and degraded during deprivation conditions. The unique nature of autophagy that clears invasive microorganisms has made it an important cellular defense mechanism in a variety of clinical situations. In recent years, it has become increasingly clear that autophagy is extensively involved in the pathology of HIV-1. To ensure survival of the virus, HIV-1 viral proteins modulate and utilize the autophagy pathway so that biosynthesis of the virus is maximized. At the same time, the abuse of illicit drugs such as methamphetamine, cocaine, morphine, and alcohol is thought to be a significant risk factor for the acquirement and progression of HIV-1. During drug-induced toxicity, autophagic activity has been proved to be altered in various cell types. Here, we review the current literature on the interaction between autophagy, HIV-1, and drug abuse and discuss the complex role of autophagy during HIV-1 pathogenesis in co exposure to illicit drugs. PMID- 27660278 TI - Correction. PMID- 27660276 TI - In Vitro Effects of Cognitives and Nootropics on Mitochondrial Respiration and Monoamine Oxidase Activity. AB - Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria. Complex I activity was decreased by galantamine, donepezil, and memantine; complex II + III activity was increased by galantamine. None of the tested drugs caused significant changes in the rate of mitochondrial oxygen consumption, even at high concentrations. Except galantamine, all tested drugs were selective MAO-A inhibitors. Latrepirdine, donepezil, and 7-MEOTA were found to be the most potent MAO-A inhibitors. Succinate-induced mitochondrial hydrogen peroxide production was not significantly affected by the drugs tested. The direct effect of cognitives and nootropics used in the treatment of AD on mitochondrial respiration is relatively small. The safest drugs in terms of disturbing mitochondrial function appear to be piracetam and rivastigmine. The MAO-A inhibition by cognitives and nootropics may also participate in mitochondrial neuroprotection. The results support the future research aimed at measuring the effects of currently used drugs or newly synthesized drugs on mitochondrial functioning in order to understand their mechanism of action. PMID- 27660277 TI - Demyelination-Induced Inflammation Attracts Newly Born Neurons to the White Matter. AB - There is compelling evidence that microglial activation negatively impacts neurogenesis. However, microglia have also been shown to promote recruitment of newly born neurons to injured areas of the gray matter. In the present study, we explored whether demyelination-triggered inflammation alters the process of neurogenesis in the white matter. A 2-MUl solution of 0.04 % ethidium bromide was stereotaxically injected into the corpus callosum of adult male rats. Brain inflammation was dampened by daily injections of progesterone (5 mg/kg, s.c.) for 14 days. Control rats received oil (s.c.). Newly born neurons (DCX and Tbr2), microglia (Iba-1), astrocytes (vimentin or GFAP), oligodendrocyte progenitor cells (OPCs; NG2), and mature oligodendrocytes (CC-1) were monitored in the vicinity of demyelination site using immunofluorescent staining. Western blot was used to explore microglial polarization using M1 (iNOS) and M2 (arginase-1) markers. Focal demyelination elicited strong microglial and astroglial activation and reduced the number of OPCs at the site of demyelination. This inflammatory response was associated with enhanced number of newly born neurons in the white matter and the subventricular zone (SVZ). A proportion of newly born neurons within the white matter showed features of OPCs. Interestingly, blunting brain inflammation led to reduced neurogenesis around the demyelination area and in the SVZ. These data suggest that the white matter inflammation creates a conducive environment for the recruitment of newly born neurons. The fact that a sizable fraction of these newly born neurons adopt OPC features suggests that they could contribute to the remyelination process. PMID- 27660279 TI - Development of a vaccine against Streptococcus agalactiae in fish based on truncated cell wall surface anchor proteins. AB - Streptococcus agalactiae is an important fish pathogen and a leading cause of major economic losses to the aquaculture industry worldwide. In the present study, the two truncated recombinant proteins of cell wall surface anchor family of S agalactiae, CWSAP465 and CWSAP1035, were expressed in Escherichia coli, and their immunogenicity and efficacy against the bacterium were evaluated in tilapia and turbot. The results showed that the prokaryotic expression of the two constructs, p32a-CWSAP465 and p32a-CWSAP1035, gave rise to a high yield of soluble proteins with good immunogenicity. The immunisation-challenge study revealed that tilapia and turbot immunised with recombinant truncated proteins produced high levels of antibodies with a peak at four weeks after immunisation and were protected from a challenge by a virulent S agalactiae at a dose of 1*109 colony forming units/ml. The recombinant truncated proteins had higher efficacy than the whole-cell inactivated vaccine. Therefore, the study demonstrated that CWSAP465 and CWSAP1035 are two viable vaccine candidates against S agalactiae in fish. PMID- 27660280 TI - Diffusion MRI of uterine and ovarian masses: identifying the benign lesions. AB - PURPOSE: The purpose of the study was to assess the diagnostic performance of qualitative and quantitative diffusion-weighted imaging (DWI) in differentiating benign from malignant ovarian and uterine masses. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant retrospective study, with waiver of informed consent. DWI MRIs of 222 women acquired over 1.5 years were evaluated. Reference standard was pathology or follow-up imaging. For qualitative assessment, two radiologists independently reviewed DWI and apparent diffusion coefficient (ADC) images for diffusion restriction. Differences were resolved by consensus. For quantitative assessment, a single reader measured ADC values. Readers were blinded to the reference standard. RESULTS: 222 lesions, 121 ovarian (99 benign and 22 malignant) and 101 uterine (54 benign and 47 malignant), were included. Final diagnosis was established with pathology in 129 (58%) or with imaging follow-up in 93 (42%). Mean (range) follow-up interval was 27 (13-48) months. Qualitative assessment yielded sensitivity (ratio, 95% CI), specificity, PPV and NPV of 100% (22/22, 85 100), 68% (68/99, 58-76), 41% (22/54, 27-54), and 100% (68/68, 94-100) for ovarian and 94% (44/47, 83-98), 91% (49/54, 80-96), 90% (44/49, 78-95) and 94% (49/52, 84-98) for uterine malignancies. ADC (mean +/- SD) between benign ovarian [(1.11 +/- 0.76) * 10-3 mm2/s] vs. malignant [(0.71 +/- 0.26) * 10-3 mm2/s] lesions was significantly different (p < 0.001). ADC cutoff value of 1.55 * 10-3 mm2/s for ovarian lesions resulted in 99.9% confidence for the absence of malignancy. ADC (mean +/- SD) of benign uterine [(0.64 +/- 0.38) * 10-3 mm2/s] vs. malignant [(0.68 +/- 0.19) * 10-3 mm2/s] lesions was not significantly different (P < 0.54). CONCLUSION: Quantitative and qualitative DWI assessment can be used to confidently characterize a subset of ovarian lesions as benign. With uterine lesions, although DWI is useful in differentiating benign from malignant lesions, the technique does not allow for definitive quantitative characterization. PMID- 27660281 TI - Detection of exocrine dysfunction by MRI in patients with early chronic pancreatitis. AB - PURPOSE: To determine if T1-weighted MR signal of the pancreas can be used to detect early CP. METHODS: A retrospective analysis was performed on 51 suspected CP patients, who had both secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) and an intraductal secretin stimulation test (IDST). There were 29 patients in normal and 22 patients in the low bicarbonate group. Bicarbonate level, total pancreatic juice volume, and excretory flow rate were recorded during IDST. Signal intensity ratio of pancreas (SIR), fat signal fraction, pancreatograms findings, and grade of duodenal filling were recorded on S-MRCP by two blinded radiologists. RESULTS: There was a significant difference in the signal intensity ratio of the pancreas to spleen (SIRp/s) between the normal and low bicarbonate groups (p < 0.0001). A significant positive correlation was found between pancreatic fluid bicarbonate level and SIRp/s (p < 0.0001). SIRp/s of 1.2 yielded sensitivity of 77% and specificity of 83% for detection of pancreatic exocrine dysfunction (AUC: 0.89). CONCLUSION: T1-weighted MR signal of the pancreas has a high sensitivity and specificity for the detection of parenchymal abnormalities related to exocrine dysfunction and can therefore be helpful in evaluation of suspected early CP. PMID- 27660284 TI - Jaw pain. PMID- 27660283 TI - The effectiveness of tobacco control policies on vulnerable populations in the USA: a review. AB - Despite population-wide efforts to reduce tobacco use, low-income populations in the USA have much higher rates of tobacco use compared with the general population. The principal components of tobacco control policies in the USA include cigarette taxes, clean indoor air laws and comprehensive interventions to increase access to tobacco cessation services. In this review, we describe the effectiveness of these policies and interventions in reducing tobacco use among vulnerable populations, focusing on persons with mental health disorders and substance use disorders, persons who have experienced incarceration or homelessness, and low-income tenants of public housing. We discuss the challenges that evolving tobacco and nicotine products pose to tobacco control efforts. We conclude by highlighting the clinical implications of treating tobacco dependence in healthcare settings that serve vulnerable populations. PMID- 27660282 TI - Cross-talk between macrophages and atrial myocytes in atrial fibrillation. AB - Increased macrophage accumulation occurs in the atria of patients with atrial fibrillation (AF). However, the phenotype and functions of the macrophages in AF remain unclear. We investigated the macrophage-atrial myocyte interaction in AF patients and found that the increased macrophages were mainly pro-inflammatory macrophages (iNOS+, Arg1-). Tachypacing of HL-1 atrial myocytes also led to pro inflammatory macrophage polarization. In addition, lipopolysaccharide (LPS) stimulated pro-inflammatory macrophages-induced atrial electrical remodeling, evidenced by increased AF incidence and decreased atrial effective refractory period and L-type calcium currents (I Ca-L) in both canine and mouse AF models. Depletion of macrophages relieved LPS-induced atrial electrical remodeling, confirming the role of pro-inflammatory macrophages in the pathogenesis of AF. We also found that the effect of LPS-stimulated macrophages on atrial myocytes was mediated by secretion of interleukin 1 beta (IL-1beta), which inhibited atrial myocyte quaking protein (QKI) expression. IL-1beta knockout in macrophages restored the LPS-stimulated macrophage-induced inhibition of QKI and CACNA1C (alpha1C subunit of L-type calcium channel) in atrial myocytes. Meanwhile, QKI overexpression in atrial myocytes restored the LPS-stimulated macrophage-induced electrical remodeling through enhanced binding of QKI to CACNA1C mRNA, which upregulated the expression of CACNA1C as well as I Ca-L. In contrast, QKI knockout inhibited CACNA1C expression. Finally, using transcription factor activation profiling plate array and chromatin immunoprecipitation, we revealed that special AT-rich sequence binding protein 1 activated QKI transcription. Taken together, our study uncovered the functional interaction between macrophages and atrial myocytes in AF. AF induced pro-inflammatory macrophage polarization while pro-inflammatory macrophages exacerbated atrial electrical remodeling by secreting IL-1beta, further inhibiting QKI expression in atrial myocytes, which contributed to I Ca-L downregulation. Our study demonstrates a novel molecular mechanism underlying the pathogenesis and progression of AF and suggests that QKI is a potential therapeutic target. PMID- 27660285 TI - The association between perceived unmet medical need and mental health among the Republic of Korea Armed Forces. AB - INTRODUCTION: We investigated the effect of unmet medical need on the mental health of Republic of Korea (ROK) Armed Forces personnel, as most of the service members work in remote areas and often experience such unmet needs. METHODS: This study used secondary data from the 2014 Military Health Survey (MHS), conducted by the ROK School of Military Medicine and designed to collect military health determinants. Descriptive statistics showed the general characteristics of the study populations by variable. We specifically compared the population after stratifying participants by suicide ideation. An analysis of variance was also carried out to compare Kessler Psychological Distress Scale 10 Scores. Additionally, dependent spouses and children of both active-duty service members and retirees are included among those entitled to Military Health System healthcare. RESULTS: Among the 4967 military personnel, 681 (13.7%) individuals reported an experience of unmet medical need within the past 12 months and gave reasons of 'no time (5.15%)', 'long office wait (2.6%)', 'no money (0.22%)', 'long distance from base (1.19%)', 'illness but not very serious (1.65%)', 'mistrust in doctors (1.95%)' and 'pressure due to performance appraisal (0.95%)'. Regression analysis revealed that unmet medical need was significantly associated with negative mental health (beta=1.753, p<0.0001) and increased suicide ideation (OR=2.649, 95% CI 1.84 to 3.82). Also, soldiers reporting unmet medical need due to 'no money', 'no time' or 'pressure due to performance appraisal' were significantly more likely to experience similar negative mental health effects. CONCLUSIONS: Our study indicates that unmet medical need is significantly associated with soldiers' mental health decline and suicide ideation, highlighting the importance of providing military personnel with timely, affordable and sufficient medical care. PMID- 27660286 TI - The High Blood Pressure-Malaria Protection Hypothesis. AB - RATIONALE: A recently proposed hypothesis states that malaria may contribute to hypertension in endemic areas,1 but the role of angiotensin II (Ang II), a major regulator of blood pressure, was not considered. Elevated levels of Ang II may confer protection against malaria morbidity and mortality, providing an alternative explanation for hypertension in malaria endemic areas. OBJECTIVE: To discuss a possible alternative cause for hypertension in populations who have been under the selective pressure of malaria. METHODS AND RESULTS: We reviewed published scientific literature for studies that could establish a link between Ang II and malaria. Both genetic and functional studies suggested that high levels of Ang II may confer protection against cerebral malaria by strengthening the integrity of the endothelial brain barrier. We also describe strong experimental evidence supporting our hypothesis through genetic, functional, and interventional studies. CONCLUSIONS: A causal association between high levels of Ang II and protection from malaria pathogenesis can provide a likely explanation for the increased prevalence in hypertension observed in populations of African and South Asian origin. Furthermore, this potential causative connection might also direct unique approaches for the effective treatment of cerebral malaria. PMID- 27660288 TI - Soluble Dietary Fiber Ameliorates Radiation-Induced Intestinal Epithelial-to Mesenchymal Transition and Fibrosis. AB - BACKGROUND: Intestinal fibrosis is a late complication of pelvic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue fibrosis. The aim of this study was to examine the effect of soluble dietary fiber on radiation-induced intestinal EMT and fibrosis in a mouse model. MATERIALS AND METHODS: Apple pectin (4% wt/wt in drinking water) was administered to wild-type and pVillin-Cre-EGFP transgenic mice with intestinal fibrosis induced by a single dose of abdominal irradiation of 10 Gy. The effects of pectin on intestinal EMT and fibrosis, gut microbiota, and short-chain fatty acid (SCFA) concentration were evaluated. RESULTS: Intestinal fibrosis in late radiation enteropathy showed increased submucosal thickness and subepithelial collagen deposition. Enhanced green fluorescent protein (EGFP)+/vimentin+ and EGFP+/alpha smooth muscle actin (SMA)+ coexpressing cells were most clearly observed at 2 weeks after irradiation and gradually decreased at 4 and 12 weeks. Pectin significantly attenuated the thickness of submucosa and collagen deposition at 12 weeks (24.3 vs 27.6 um in the pectin + radiation-treated group compared with radiation-alone group, respectively, P < .05; 69.0% vs 57.1%, P < .001) and ameliorated EMT at 2 and 4 weeks. Pectin also modulated the intestinal microbiota composition and increased the luminal SCFA concentration. CONCLUSION: The soluble dietary fiber pectin protected the terminal ileum against radiation-induced fibrosis. This effect might be mediated by altered SCFA concentration in the intestinal lumen and reduced EMT in the ileal epithelium. PMID- 27660287 TI - Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature Hypertension in the Spontaneously Hypertensive Rat. AB - RATIONALE: Renal inflammation contributes to the pathophysiology of hypertension. CD161a+ immune cells are dominant in the (SHR) spontaneously hypertensive rat and expand in response to nicotinic cholinergic activation. OBJECTIVE: We aimed to phenotype CD161a+ immune cells in prehypertensive SHR after cholinergic activation with nicotine and determine if these cells are involved in renal inflammation and the development of hypertension. METHODS AND RESULTS: Studies used young SHR and WKY (Wistar-Kyoto) rats. Splenocytes and bone marrow cells were exposed to nicotine ex vivo, and nicotine was infused in vivo. Blood pressures, kidney, serum, and urine were obtained. Flow cytometry, Luminex/ELISA, immunohistochemistry, confocal microscopy, and Western blot were used. Nicotinic cholinergic activation induced proliferation of CD161a+/CD68+ macrophages in SHR derived splenocytes, their renal infiltration, and premature hypertension in SHR. These changes were associated with increased renal expression of MCP-1 (monocyte chemoattractant protein-1) and VLA-4 (very-late antigen-4). LLT1 (lectin-like transcript 1), the ligand for CD161a, was overexpressed in SHR kidney, whereas vascular cellular and intracellular adhesion molecules were similar to those in WKY. Inflammatory cytokines were elevated in SHR kidney and urine after nicotine infusion. Nicotine-mediated renal macrophage infiltration/inflammation was enhanced in denervated kidneys, not explained by angiotensin II levels or expression of angiotensin type-1/2 receptors. Moreover, expression of the anti inflammatory alpha7-nAChR (alpha7-nicotinic acetylcholine receptor) was similar in young SHR and WKY rats. CONCLUSIONS: A novel, inherited nicotinic cholinergic inflammatory effect exists in young SHR, measured by expansion of CD161a+/CD68+ macrophages. This leads to renal inflammation and premature hypertension, which may be partially explained by increased renal expression of LLT-1, MCP-1, and VLA 4. PMID- 27660290 TI - Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text]. AB - BACKGROUND: We aim to study the efficacy of exogenously administered glucagon like peptide 2 (GLP-2) on intestinal adaptation in 2 preclinical models of neonatal short bowel syndrome (SBS) according to remnant intestinal anatomy, with and without ileum. Furthermore, we aim to determine if this adaptive effect was potentiated with enteral nutrition (EN). METHODS: Neonatal piglets were block randomized to 75% mid-intestinal (JI group, retains ileum) or distal-intestinal (JC group, has no ileum) resection or no resection (sham control) and GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets received nutrition support, either 100% parenteral nutrition (PN; 0% EN, n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Adaptation was assessed by morphological and histological changes, as well as RT quantitative polymerase chain reaction of nutrient transporters and tight junctional proteins and fat absorption. Data are analyzed by 3-way analysis of variance (ANOVA) and 2-way ANOVA per EN level. RESULTS: GLP-2 treatment lengthened villi, deepened crypts, and improved intestinal weight in the remnant intestine of JC piglets. EN was a more potent adaptive stimulus for JI piglets. Small intestinal lengthening occurred only in the JI group, when given EN. There was no difference in total fat absorption and messenger RNA expression of nutrient transporters and tight junctional proteins. CONCLUSIONS: GLP-2 administration augmented structural adaptation in JC piglets with distal intestinal resection. Given JI anatomy, further stimulation by GLP-2 treatment over innate adaptation and stimulation by EN was modest and restricted to ileum. The differential effect of GLP-2 in neonatal SBS, depending on remnant anatomy, has important implications for clinical translation and planning of clinical trials. PMID- 27660291 TI - Personal responsibility within health policy: unethical and ineffective. AB - This paper argues against incorporating assessments of individual responsibility into healthcare policies by expanding an existing argument and offering a rebuttal to an argument in favour of such policies. First, it is argued that what primarily underlies discussions surrounding personal responsibility and healthcare is not causal responsibility, moral responsibility or culpability, as one might expect, but biases towards particular highly stigmatised behaviours. A challenge is posed for proponents of taking personal responsibility into account within health policy to either expand the debate to also include socially accepted behaviours or to provide an alternative explanation of the narrowly focused discussion. Second, a critical response is offered to arguments that claim that policies based on personal responsibility would lead to several positive outcomes including healthy behaviour change, better health outcomes and decreases in healthcare spending. It is argued that using individual responsibility as a basis for resource allocation in healthcare is unlikely to motivate positive behaviour changes, and is likely to increase inequality which may lead to worse health outcomes overall. Finally, the case of West Virginia's Medicaid reform is examined, which raises a worry that policies focused on personal responsibility have the potential to lead to increases in medical spending overall. PMID- 27660292 TI - Comparison of Postoperative Height Changes of the Second Metatarsal Among 3 Osteotomy Methods for Hallux Valgus Deformity Correction. AB - BACKGROUND: We aimed to compare the postoperative height of the second metatarsal head relative to the first metatarsal head using axial radiographs among 3 different commonly used osteotomy techniques: proximal chevron metatarsal osteotomy (PCMO), scarf osteotomy, and distal chevron metatarsal osteotomy (DCMO). METHODS: We retrospectively reviewed the radiographs and clinical findings of the patients with painful callosities under the second metatarsal head, complicated by hallux valgus, who underwent isolated PCMO, scarf osteotomy, or DCMO from February 2005 to January 2015. Each osteotomy was performed with 20 degrees of plantar ward obliquity. Along with lateral translation and rotation of the distal fragment to correct the deformity, lowering of the first metatarsal head was made by virtue of the oblique metatarsal osteotomy. RESULTS: Significant postoperative change in the second metatarsal height was observed on axial radiographs in all groups; this value was greatest in the PCMO group (vs scarf: P = .013; vs DCMO: P = .008) but did not significantly differ between the scarf and DCMO groups ( P = .785). The power for second metatarsal height correction was significantly greater in the PCMO group (vs scarf: P = .0005; vs DCMO: P = .0005) but did not significantly differ between the scarf and DCMO groups ( P = .832). CONCLUSIONS: Among the 3 osteotomy techniques commonly used to correct hallux valgus deformity, we observed that PCMO yielded the most effective height change of the second metatarsal head. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 27660289 TI - Interaction Between 2 Nutraceutical Treatments and Host Immune Status in the Pediatric Critical Illness Stress-Induced Immune Suppression Comparative Effectiveness Trial. AB - BACKGROUND AND AIMS: The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis. METHODS: Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category. RESULTS: There were 134 immune competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P < .05) and on the rate of nosocomial infection and sepsis per 100 patient days ( P < .05). Whey protein treatment protected immune-competent patients without lymphopenia from infection and sepsis, both nutraceutical strategies were equivalent in immune-competent patients with lymphopenia, and zinc, selenium, glutamine, and metoclopramide treatment protected immunocompromised patients from infection and sepsis. CONCLUSIONS: The science of immune nutrition is more complex than previously thought. Future trial design should consider immune status at the time of trial entry because differential effects of nutraceuticals may be related to this patient characteristic. PMID- 27660293 TI - Restoration of Hydrogen Sulfide Production in Diabetic Mice Improves Reparative Function of Bone Marrow Cells. AB - BACKGROUND: Bone marrow cell (BMC)-based treatment for critical limb ischemia in diabetic patients yielded a modest therapeutic effect resulting from cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functions may provide therapeutic benefits. Here, we tested the hypothesis that restoration of hydrogen sulfide (H2S) production in diabetic BMCs improves their reparative capacities. METHODS: Mouse BMCs were isolated by density-gradient centrifugation. Unilateral hind limb ischemia was conducted in 12- to 14-week-old db/+ and db/db mice by ligation of the left femoral artery. The H2S level was measured by either gas chromatography or staining with florescent dye sulfidefluor 7 AM. RESULTS: Both H2S production and cystathionine gamma-lyase (CSE), an H2S enzyme, levels were significantly decreased in BMCs from diabetic db/db mice. Administration of H2S donor diallyl trisulfide (DATS) or overexpression of CSE restored H2S production and enhanced cell survival and migratory capacity in high glucose (HG)-treated BMCs. Immediately after hind limb ischemia surgery, the db/+ and db/db mice were administered DATS orally and/or given a local intramuscular injection of green fluorescent protein-labeled BMCs or red fluorescent protein-CSE-overexpressing BMCs (CSE-BMCs). Mice with hind limb ischemia were divided into 6 groups: db/+, db/db, db/db+BMCs, db/db+DATS, db/db+DATS+BMCs, and db/db+CSE-BMCs. DATS and CSE overexpression greatly enhanced diabetic BMC retention in ischemic hind limbs followed by improved blood perfusion, capillary/arteriole density, skeletal muscle architecture, and cell survival and decreased perivascular CD68+ cell infiltration in the ischemic hind limbs of diabetic mice. It is interesting to note that DATS or CSE overexpression rescued high glucose-impaired migration, tube formation, and survival of BMCs or mature human cardiac microvascular endothelial cells. Moreover, DATS restored nitric oxide production and decreased endothelial nitric oxide synthase phosphorylation at threonine 495 levels in human cardiac microvascular endothelial cells and improved BMC angiogenic activity under high glucose condition. Last, silencing CSE by siRNA significantly increased endothelial nitric oxide synthase phosphorylation at threonine 495 levels in human cardiac microvascular endothelial cells. CONCLUSIONS: Decreased CSE-mediated H2S bioavailability is an underlying source of BMC dysfunction in diabetes mellitus. Our data indicate that H2S and overexpression of CSE in diabetic BMCs may rescue their dysfunction and open novel avenues for cell-based therapeutics of critical limb ischemia in diabetic patients. PMID- 27660295 TI - Selective Sweeps across Twenty Millions Years of Primate Evolution. AB - The contribution from selective sweeps to variation in genetic diversity has proven notoriously difficult to assess, in part because polymorphism data only allows detection of sweeps in the most recent few hundred thousand years. Here, we show how linked selection in ancestral species can be quantified across evolutionary timescales by analyzing patterns of incomplete lineage sorting (ILS) along the genomes of closely related species. We show that sweeps in the human chimpanzee and human-orangutan ancestors can be identified as depletions of ILS in regions in excess of 100 kb in length. Sweeps predicted in each ancestral species, as well as recurrent sweeps predicted in both species, often overlap sweeps predicted in humans. This suggests that many genomic regions experience recurrent selective sweeps. By comparing the ILS patterns along the genomes of the closely related human-chimpanzee and human-orangutan ancestors, we are further able to quantify the impact of selective sweeps relative to that of background selection. Compared with the human-orangutan ancestor, the human chimpanzee ancestor shows a strong excess of regions depleted of ILS as well as a stronger reduction in ILS around genes. We conclude that sweeps play a strong role in reducing diversity along the genome and that sweeps have reduced diversity in the human-chimpanzee ancestor much more than in the human-orangutan ancestor. PMID- 27660294 TI - Cathepsin G Controls Arterial But Not Venular Myeloid Cell Recruitment. AB - BACKGROUND: Therapeutic targeting of arterial leukocyte recruitment in the context of atherosclerosis has been disappointing in clinical studies. Reasons for such failures include the lack of knowledge of arterial-specific recruitment patterns. Here we establish the importance of the cathepsin G (CatG) in the context of arterial myeloid cell recruitment. METHODS: Intravital microscopy of the carotid artery, the jugular vein, and cremasteric arterioles and venules in Apoe-/-and CatG-deficient mice (Apoe-/-Ctsg-/-) was used to study site-specific myeloid cell behavior after high-fat diet feeding or tumor necrosis factor stimulation. Atherosclerosis development was assessed in aortic root sections after 4 weeks of high-fat diet, whereas lung inflammation was assessed after inhalation of lipopolysaccharide. Endothelial deposition of CatG and CCL5 was quantified in whole-mount preparations using 2-photon and confocal microscopy. RESULTS: Our observations elucidated a crucial role for CatG during arterial leukocyte adhesion, an effect not found during venular adhesion. Consequently, CatG deficiency attenuates atherosclerosis but not acute lung inflammation. Mechanistically, CatG is immobilized on arterial endothelium where it activates leukocytes to firmly adhere engaging integrin clustering, a process of crucial importance to achieve effective adherence under high-shear flow. Therapeutic neutralization of CatG specifically abrogated arterial leukocyte adhesion without affecting myeloid cell adhesion in the microcirculation. Repetitive application of CatG-neutralizing antibodies permitted inhibition of atherogenesis in mice. CONCLUSIONS: Taken together, these findings present evidence of an arterial specific recruitment pattern centered on CatG-instructed adhesion strengthening. The inhibition of this process could provide a novel strategy for treatment of arterial inflammation with limited side effects. PMID- 27660296 TI - A Photoreceptor Contributes to the Natural Variation of Diapause Induction in Daphnia magna. AB - Diapause is an adaptation that allows organisms to survive harsh environmental conditions. In species occurring over broad habitat ranges, both the timing and the intensity of diapause induction can vary across populations, revealing patterns of local adaptation. Understanding the genetic architecture of this fitness-related trait would help clarify how populations adapt to their local environments. In the cyclical parthenogenetic crustacean Daphnia magna, diapause induction is a phenotypic plastic life history trait linked to sexual reproduction, as asexual females have the ability to switch to sexual reproduction and produce resting stages, their sole strategy for surviving habitat deterioration. We have previously shown that the induction of resting stage production correlates with changes in photoperiod that indicate the imminence of habitat deterioration and have identified a Quantitative Trait Locus (QTL) responsible for some of the variation in the induction of resting stages. Here, new data allows us to anchor the QTL to a large scaffold and then, using a combination of a new mapping panel, targeted association mapping and selection analysis in natural populations, to identify candidate genes within the QTL. Our results show that variation in a rhodopsin photoreceptor gene plays a significant role in the variation observed in resting stage induction. This finding provides a mechanistic explanation for the link between diapause and day-length perception that has been suggested in diverse arthropod taxa. PMID- 27660297 TI - Pulmonary artery pressure and arterial oxygen saturation in people living at high or low altitude: systematic review and meta-analysis. AB - More than 140 million people are living at high altitude worldwide. An increase of pulmonary artery pressure (PAP) is a hallmark of high-altitude exposure and, if pronounced, may be associated with important morbidity and mortality. Surprisingly, there is little information on the usual PAP in high-altitude populations. We, therefore, conducted a systematic review (MEDLINE and EMBASE) and meta-analysis of studies published (in English or Spanish) between 2000 and 2015 on echocardiographic estimations of PAP and measurements of arterial oxygen saturation in apparently healthy participants from general populations of high altitude dwellers (>2,500 m). For comparison, we similarly analyzed data published on these variables during the same period for populations living at low altitude. Twelve high-altitude studies comprising 834 participants and 18 low altitude studies (710 participants) fulfilled the inclusion criteria. All but one high-altitude studies were performed between 3,600 and 4,350 m. The combined mean systolic PAP (right ventricular-to-right atrial pressure gradient) at high altitude [25.3 mmHg, 95% confidence interval (CI) 24.0, 26.7], as expected was significantly (P < 0.001) higher than at low altitude (18.4 mmHg, 95% CI 17.1,19.7), and arterial oxygen saturation was significantly lower (90.4%, 95% CI 89.3, 91.5) than at low altitude (98.1%; 95% CI 97.7, 98.4). These findings indicate that at an altitude where the very large majority of high-altitude populations are living, pulmonary hypertension appears to be rare. The reference values and distributions for PAP and arterial oxygen saturation in apparently healthy high-altitude dwellers provided by this meta-analysis will be useful to future studies on the adjustments to high altitude in humans. PMID- 27660298 TI - Case Studies in Physiology: Ventilation and perfusion in a giraffe-does size matter? AB - The trachea in the giraffe is long but narrow, and dead space ventilation is considered to be of approximately the same size as in other mammals. Less is known about the matching between ventilation and lung blood flow. The lungs in the giraffe are large, up to 1 m high and 0.7 m wide, and this may cause considerable ventilation/perfusion (VA/Q) mismatch due to the influence of gravitational forces, which could lead to hypoxemia. We studied a young giraffe under anesthesia using the multiple inert gas elimination technique to analyze the VA/Q distribution and arterial oxygenation and compared the results with those obtained in other species of different sizes, including humans. VA/Q distribution was broad but unimodal, and the shunt of blood flow through nonventilated lung regions was essentially absent, suggesting no lung collapse. The VA/Q match was as good as in the similarly sized horse and was even comparable to that in smaller sized animals, including rabbit and rat. The match was also similar to that in anesthetized humans. Arterial oxygenation was essentially similar in all studied species. The findings suggest that the efficiency of VA/Q matching is independent of lung size in the studied mammals that vary in weight from less than 1 to more than 400 kg. PMID- 27660300 TI - Skeletal muscle power and fatigue at the tolerable limit of ramp-incremental exercise in COPD. AB - Muscle fatigue (a reduced power for a given activation) is common following exercise in chronic obstructive pulmonary disease (COPD). Whether muscle fatigue, and reduced maximal voluntary locomotor power, are sufficient to limit whole body exercise in COPD is unknown. We hypothesized in COPD: 1) exercise is terminated with a locomotor muscle power reserve; 2) reduction in maximal locomotor power is related to ventilatory limitation; and 3) muscle fatigue at intolerance is less than age-matched controls. We used a rapid switch from hyperbolic to isokinetic cycling to measure the decline in peak isokinetic power at the limit of incremental exercise ("performance fatigue") in 13 COPD patients (FEV1 49 +/- 17%pred) and 12 controls. By establishing the baseline relationship between muscle activity and isokinetic power, we apportioned performance fatigue into the reduction in muscle activation and muscle fatigue. Peak isokinetic power at intolerance was ~130% of peak incremental power in controls (274 +/- 73 vs. 212 +/- 84 W, P < 0.05), but ~260% in COPD patients (187 +/- 141 vs. 72 +/- 34 W, P < 0.05), greater than controls (P < 0.05). Muscle fatigue as a fraction of baseline peak isokinetic power was not different in COPD patients vs. controls (0.11 +/- 0.20 vs. 0.19 +/- 0.11). Baseline to intolerance, the median frequency of maximal isokinetic muscle activity, was unchanged in COPD patients but reduced in controls (+4.3 +/- 11.6 vs. -5.5 +/- 7.6%, P < 0.05). Performance fatigue as a fraction of peak incremental power was greater in COPD vs. controls and related to resting (FEV1/FVC) and peak exercise (VE/maximal voluntary ventilation) pulmonary function (r2 = 0.47 and 0.55, P < 0.05). COPD patients are more fatigable than controls, but this fatigue is insufficient to constrain locomotor power and define exercise intolerance. PMID- 27660301 TI - Bouncing on Mars and the Moon-the role of gravity on neuromuscular control: correlation of muscle activity and rate of force development. AB - On our astronomical neighbors Mars and the Moon, bouncing movements are the preferred locomotor techniques. During bouncing, the stretch-shortening cycle describes the muscular activation pattern. This study aimed to identify gravity dependent changes in kinematic and neuromuscular characteristics in the stretch shortening cycle. Hence, neuromuscular control of limb muscles as well as correlations between the muscles' pre-activation, reflex components, and force output were assessed in lunar, Martian, and Earth gravity. During parabolic flights, peak force (Fmax), ground-contact-time, rate of force development (RFD), height, and impulse were measured. Electromyographic (EMG) activities in the m. soleus (SOL) and gastrocnemius medialis (GM) were assessed before (PRE) and during bounces for the reflex phases short-, medium-, and long-latency response (SLR, MLR, LLR). With gradually decreasing gravitation, Fmax, RFD, and impulse were reduced, whereas ground-contact time and height increased. Concomitantly, EMG_GM decreased for PRE, SLR, MLR, and LLR, and in EMG_SOL in SLR, MLR, and LLR. For SLR and MLR, Fmax and RFD were positively correlated to EMG_SOL. For PRE and LLR, RFD and Fmax were positively correlated to EMG_GM. Findings emphasize that biomechanically relevant kinematic adaptations in response to gravity variation were accompanied by muscle- and phase-specific modulations in neural control. Gravitational variation is anticipated and compensated for by gravity-adjusted muscle activities. Importantly, the pre-activation and reflex phases were differently affected: in SLR and MLR, SOL is assumed to contribute to the decline in force output with a decreasing load, and, complementary in PRE and LLR, GM seems to be of major importance for force generation. PMID- 27660299 TI - Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats. AB - Abdominal expiratory activity is absent at rest and is evoked during metabolic challenges, such as hypercapnia and hypoxia, or after the exposure to intermittent hypoxia (IH). The mechanisms engaged during this process are not completely understood. In this study, we hypothesized that serotonin (5-HT), acting in the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), is able to generate active expiration. In anesthetized (urethane, ip), tracheostomized, spontaneously-breathing adult male Holtzman rats we microinjected a serotoninergic agonist and antagonist bilaterally in the RTN/pFRG and recorded diaphragm and abdominal muscle activities. We found that episodic (3 times, 5 min apart), but not single microinjections of 5-HT (1 mM) in the RTN/pFRG elicited an enduring (>30 min) increase in abdominal activity. This response was amplified in vagotomized rats and blocked by previous 5-HT receptor antagonism with ketanserin (10 uM). Episodic 5-HT microinjections in the RTN/pFRG also potentiated the inspiratory and expiratory reflex responses to hypercapnia. The antagonism of 5-HT receptors in the RTN/pFRG also prevented the long-term facilitation (>30 min) of abdominal activity in response to acute IH exposure (10 * 6-7% O for 45 s every 5 min). Our findings indicate the activation of serotoninergic mechanisms in the RTN/pFRG is sufficient to increase abdominal expiratory activity at resting conditions and required for the emergence of active expiration after IH in anesthetized animals. PMID- 27660302 TI - Statistical Methods for Cohort Studies of CKD: Prediction Modeling. AB - Prediction models are often developed in and applied to CKD populations. These models can be used to inform patients and clinicians about the potential risks of disease development or progression. With increasing availability of large datasets from CKD cohorts, there is opportunity to develop better prediction models that will lead to more informed treatment decisions. It is important that prediction modeling be done using appropriate statistical methods to achieve the highest accuracy, while avoiding overfitting and poor calibration. In this paper, we review prediction modeling methods in general from model building to assessing model performance as well as the application to new patient populations. Throughout, the methods are illustrated using data from the Chronic Renal Insufficiency Cohort Study. PMID- 27660303 TI - Anxiety in Patients Treated with Hemodialysis. AB - Anxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients' perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD. PMID- 27660304 TI - Crackles and Comets: Lung Ultrasound to Detect Pulmonary Congestion in Patients on Dialysis is Coming of Age. PMID- 27660305 TI - The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study. AB - BACKGROUND AND OBJECTIVES: Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. RESULTS: Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and kappa-statistics (kappa ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. CONCLUSIONS: Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis. PMID- 27660306 TI - Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US Department of Veterans Affairs, 2000-2011. AB - BACKGROUND AND OBJECTIVES: It is not known what proportion of United States patients with advanced CKD go on to receive RRT. In other developed countries, receipt of RRT is highly age dependent and the exception rather than the rule at older ages. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective study of a national cohort of 28,568 adults who were receiving care within the US Department of Veteran Affairs and had a sustained eGFR <15 ml/min per 1.73 m2 between January 1, 2000 to December 31, 2009. We used linked administrative data from the US Renal Data System, US Department of Veteran Affairs, and Medicare to identify cohort members who received RRT during follow up through October 1, 2011 (n=19,165). For a random 25% sample of the remaining 9403 patients, we performed an in-depth review of their VA-wide electronic medical records to determine the treatment status of their CKD. RESULTS: Two thirds (67.1%) of cohort members received RRT on the basis of administrative data. On the basis of the results of chart review, we estimate that an additional 7.5% (95% confidence interval, 7.2% to 7.8%) of cohort members had, in fact, received dialysis, that 10.9% (95% confidence interval, 10.6% to 11.3%) were preparing for and/or discussing dialysis but had not started dialysis at most recent follow-up, and that a decision had been made not to pursue dialysis in 14.5% (95% confidence interval, 14.1% to 14.9%). The percentage of cohort members who received or were preparing to receive RRT ranged from 96.2% (95% confidence interval, 94.4% to 97.4%) for those <45 years old to 53.3% (95% confidence interval, 50.7% to 55.9%) for those aged >=85 years old. Results were similar after stratification by tertile of Gagne comorbidity score. CONCLUSIONS: In this large United States cohort of patients with advanced CKD, the majority received or were preparing to receive RRT. This was true even among the oldest patients with the highest burden of comorbidity. PMID- 27660307 TI - Practice Change Is Needed for Dialysis Decision Making with Older Adults with Advanced Kidney Disease. PMID- 27660308 TI - Intracellular cholesterol transport proteins: roles in health and disease. AB - Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors, and enzymes, receptors and transporters subject to post-transcriptional and post-translational regulation, whereas loss of these elegant, tightly regulated homoeostatic responses is integral to disease pathologies. Recent data suggest that sterol-binding sensors, exchangers and transporters contribute to regulation of cellular cholesterol homoeostasis and that genetic overexpression or deletion, or mutations, in a number of these proteins are linked with diseases, including atherosclerosis, dyslipidaemia, diabetes, congenital lipoid adrenal hyperplasia, cancer, autosomal dominant hearing loss and male infertility. This review focuses on current evidence exploring the function of members of the 'START' (steroidogenic acute regulatory protein-related lipid transfer) and 'ORP' (oxysterol-binding protein-related proteins) families of sterol-binding proteins in sterol homoeostasis in eukaryotic cells, and the evidence that they represent valid therapeutic targets to alleviate human disease. PMID- 27660309 TI - The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease. AB - Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alters metabolism, proliferation, apoptosis and mitophagy, contributing to human diseases, including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), cancer and ischemia/reperfusion injury. Post-translational regulation of Drp1 (by phosphorylation and SUMOylation) is an established means of modulating Drp1 activation and translocation to the outer mitochondrial membrane (OMM). This review focuses on Drp1 adaptor proteins that also regulate fission. The proteins include fission 1 (Fis1), mitochondrial fission factor (Mff) and mitochondrial dynamics proteins of 49 kDa and 51 kDa (MiD49, MiD51). Heterologous MiD overexpression sequesters inactive Drp1 on the OMM, promoting fusion; conversely, increased endogenous MiD creates focused Drp1 multimers that optimize OMM scission. The triggers that activate MiD-bound Drp1 in disease states are unknown; however, MiD51 has a unique capacity for ADP binding at its nucleotidyltransferase domain. Without ADP, MiD51 inhibits Drp1, whereas ADP promotes MiD51-mediated fission, suggesting a link between metabolism and fission. Confusion over whether MiDs mediate fusion (by sequestering inactive Drp1) or fission (by guiding Drp1 assembly) relates to a failure to consider cell types used and to distinguish endogenous compared with heterologous changes in expression. We speculate that endogenous MiDs serve as Drp1-binding partners that are dysregulated in disease states and may be important targets for inhibiting cell proliferation and ischemia/reperfusion injury. Moreover, it appears that the composition of the fission apparatus varies between disease states and amongst individuals. MiDs may be important targets for inhibiting cell proliferation and attenuating ischemia/reperfusion injury. PMID- 27660310 TI - Small vessels, dementia and chronic diseases-molecular mechanisms and pathophysiology. PMID- 27660311 TI - Clinical challenges in the diagnosis and management of postural tachycardia syndrome. AB - Postural tachycardia syndrome (POTS) is a multifactorial clinical syndrome defined by an increase in heart rate of >=30 bpm on standing from supine position (or >=40 bpm in children). It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve when in supine position. Patients often have additional symptoms including severe fatigue and difficulty concentrating. There are several possible pathophysiologic mechanisms including hypovolaemia, small-fibre peripheral neuropathy and hyperadrenergic states. POTS can also be associated with several disorders including mastocytosis, Ehlers Danlos syndrome (hypermobility type) and autoimmune disorders. The treatment is focused on symptom relief and not solely on reducing tachycardia. Given its varying presentations, it is important to employ a practical, mechanism-focused approach to the diagnosis and management of POTS. PMID- 27660312 TI - Maternal vitamin D deficiency and fetal distress/birth asphyxia: a population based nested case-control study. AB - OBJECTIVE: Vitamin D deficiency causes not only skeletal problems but also muscle weakness, including heart muscle. If the fetal heart is also affected, it might be more susceptible to fetal distress and birth asphyxia. In this pilot study, we hypothesised that low maternal vitamin D levels are over-represented in pregnancies with fetal distress/birth asphyxia. DESIGN AND SETTING: A population based nested case-control study. PATIENTS: Banked sera of 2496 women from the 12th week of pregnancy. OUTCOME MEASURES: Vitamin D levels were analysed using a direct competitive chemiluminescence immunoassay. Vitamin D levels in early gestation in women delivered by emergency caesarean section due to suspected fetal distress were compared to those in controls. Birth asphyxia was defined as Apgar <7 at 5 min and/or umbilical cord pH<=7.15. RESULTS: Vitamin D levels were significantly lower in mothers delivered by emergency caesarean section due to suspected fetal distress (n=53, 43.6+/-18 nmol/L) compared to controls (n=120, 48.6+/-19 nmol/L, p=0.04). Birth asphyxia was more common in women with vitamin D deficiency (n=95) in early pregnancy (OR 2.4, 95% CI 1.1 to 5.7). CONCLUSIONS: Low vitamin D levels in early pregnancy may be associated with emergency caesarean section due to suspected fetal distress and birth asphyxia. If our findings are supported by further studies, preferably on severe birth asphyxia, vitamin D supplementation/sun exposure in pregnancy may lower the risk of subsequent birth asphyxia. PMID- 27660313 TI - Improving institutional childbirth services in rural Southern Tanzania: a qualitative study of healthcare workers' perspective. AB - OBJECTIVE: To describe health workers' perceptions of a quality improvement (QI) intervention that focused on improving institutional childbirth services in primary health facilities in Southern Tanzania. DESIGN: A qualitative design was applied using in-depth interviews with health workers. SETTING: This study involved the Ruangwa District Reproductive and Child Health Department, 11 dispensaries and 2 health centres in rural Southern Tanzania. PARTICIPANTS: 4 clinical officers, 5 nurses and 6 medical attendants from different health facilities were interviewed. RESULTS: The healthcare providers reported that the QI intervention improved their skills, capacity and confidence in providing counselling and use of a partograph during labour. The face-to-face QI workshops, used as a platform to refresh their knowledge on maternal and newborn health and QI methods, facilitated peer learning, networking and standardisation of care provision. The onsite follow-up visits were favoured by healthcare providers because they gave the opportunity to get immediate help, learn how to perform tasks in practice and be reminded of what they had learnt. Implementation of parallel interventions focusing on similar indicators was mentioned as a challenge that led to duplication of work in terms of data collection and reporting. District supervisors involved in the intervention showed interest in taking over the implementation; however, funding remained a major obstacle. CONCLUSIONS: Healthcare workers highlighted the usefulness of applying a QI approach to improve maternal and newborn health in rural settings. QI programmes need careful coordination at district level in order to reduce duplication of work. PMID- 27660315 TI - Economic costs of chronic disease through lost productive life years (PLYs) among Australians aged 45-64 years from 2015 to 2030: results from a microsimulation model. AB - OBJECTIVES: To project the number of older workers with lost productive life years (PLYs) due to chronic disease and resultant lost income; and lost taxes and increased welfare payments from 2015 to 2030. DESIGN, SETTING AND PARTICIPANTS: Using a microsimulation model, Health&WealthMOD2030, the costs of chronic disease in Australians aged 45-64 were projected to 2030. The model integrates household survey data from the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers (SDACs) 2003 and 2009, output from long-standing microsimulation models (STINMOD (Static Incomes Model) and APPSIM (Australian Population and Policy Simulation Model)) used by various government departments, population and labour force growth data from Treasury, and disease trends data from the Australian Burden of Disease and Injury Study (2003). Respondents aged 45-64 years in the SDACs 2003 and 2009 formed the base population. MAIN OUTCOME MEASURES: Lost PLYs due to chronic disease; resultant lost income, lost taxes and increased welfare payments in 2015, 2020, 2025 and 2030. RESULTS: We projected 380 000 (6.4%) people aged 45-64 years with lost PLYs in 2015, increasing to 462 000 (6.5%) in 2030-a 22% increase in absolute numbers. Those with lost PLYs experience the largest reduction in income than any other group in each year compared to those employed full time without a chronic disease, and this income gap widens over time. The total economic loss due to lost PLYs consisted of lost income modelled at $A12.6 billion in 2015, increasing to $A20.5 billion in 2030-a 62.7% increase. Additional costs to the government consisted of increased welfare payments at $A6.2 billion in 2015, increasing to $A7.3 billion in 2030-a 17.7% increase; and a loss of $A3.1 billion in taxes in 2015, increasing to $A4.7 billion in 2030-a growth of 51.6%. CONCLUSIONS: There is a need for greater investment in effective preventive health interventions which improve workers' health and work capacity. PMID- 27660314 TI - Effective psychological and psychosocial approaches to reduce repetition of self harm: a systematic review, meta-analysis and meta-regression. AB - OBJECTIVE: To examine the efficacy of psychological and psychosocial interventions for reductions in repeated self-harm. DESIGN: We conducted a systematic review, meta-analysis and meta-regression to examine the efficacy of psychological and psychosocial interventions to reduce repeat self-harm in adults. We included a sensitivity analysis of studies with a low risk of bias for the meta-analysis. For the meta-regression, we examined whether the type, intensity (primary analyses) and other components of intervention or methodology (secondary analyses) modified the overall intervention effect. DATA SOURCES: A comprehensive search of MEDLINE, PsycInfo and EMBASE (from 1999 to June 2016) was performed. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of psychological and psychosocial interventions for adult self-harm patients. RESULTS: Forty-five trials were included with data available from 36 (7354 participants) for the primary analysis. Meta-analysis showed a significant benefit of all psychological and psychosocial interventions combined (risk ratio 0.84; 95% CI 0.74 to 0.96; number needed to treat=33); however, sensitivity analyses showed that this benefit was non-significant when restricted to a limited number of high-quality studies. Meta-regression showed that the type of intervention did not modify the treatment effects. CONCLUSIONS: Consideration of a psychological or psychosocial intervention over and above treatment as usual is worthwhile; with the public health benefits of ensuring that this practice is widely adopted potentially worth the investment. However, the specific type and nature of the intervention that should be delivered is not yet clear. Cognitive behavioural therapy or interventions with an interpersonal focus and targeted on the precipitants to self-harm may be the best candidates on the current evidence. Further research is required. PMID- 27660316 TI - Evaluation of 'I-Preventive': a digital preventive tool for musculoskeletal disorders in computer workers-a pilot cluster randomised trial. AB - OBJECTIVES: I-Preventive is a digital preventive tool for musculoskeletal disorders (MSDs) in computer workers. We sought to determine its impact on pain in computer workers with upper limb MSDs and visual discomfort. METHODS: We conducted a pilot cluster randomised trial in 2 different sites of a tyre factory in France. We randomised 200 employees to either an intervention group (I Preventive) or control group, each comprising symptomatic and asymptomatic employees. The workers were followed up for 5 months. The main outcome was overall recovery from symptoms following 1 month's intervention based on Nordic style and eyestrain questionnaires. RESULTS: We included 185/200 workers: 96 in the intervention group (mean age 41.8+/-1.4 years; 88.5% males) and 79 in the control group (mean age 42.9+/-12.0 years; 94.5% males). The most painful areas (numerical scale >=2) were the neck (40.0%), upper back (18.8%) and shoulders (15.7%). For the most painful anatomical area, the Nordic score significantly decreased after 1 month in the intervention group (p=0.038); no change was observed in the control group (p=0.59). After 1 month's use, the intervention group reported less pain in the painful area and less visual discomfort symptoms (p=0.02). Adherence to the I-Preventive program was 60%. CONCLUSIONS: I Preventive is effective in the short term on musculoskeletal symptoms and visual discomfort by promoting active breaks and eyestrain treatment. This easy-to-use digital tool allows each worker to focus on areas of their choice via personalised, easy exercises that can be performed in the workplace. TRIAL REGISTRATION NUMBER: NCT02350244; Pre-results. PMID- 27660317 TI - Multimethod study of a large-scale programme to improve patient safety using a harm-free care approach. AB - OBJECTIVES: We aimed to evaluate whether a large-scale two-phase quality improvement programme achieved its aims and to characterise the influences on achievement. SETTING: National Health Service (NHS) in England. PARTICIPANTS: NHS staff. INTERVENTIONS: The programme sought to (1) develop a shared national, regional and locally aligned safety focus for 4 high-cost, high volume harms; (2) establish a new measurement system based on a composite measure of 'harm-free' care and (3) deliver improved outcomes. Phase I involved a quality improvement collaborative intended to involve 100 organisations; phase II used financial incentives for data collection. MEASURES: Multimethod evaluation of the programme. In phase I, analysis of regional plans and of rates of data submission and clinical outcomes reported to the programme. A concurrent process evaluation was conducted of phase I, but only data on submission rates and clinical outcomes were available for phase II. RESULTS: A context of extreme policy-related structural turbulence impacted strongly on phase I. Most regions' plans did not demonstrate full alignment with the national programme; most fell short of recruitment targets and attrition in attendance at the collaborative meetings occurred over time. Though collaborative participants saw the principles underlying the programme as attractive, useful and innovative, they often struggled to convert enthusiasm into change. Developing the measurement system was arduous, yet continued to be met by controversy. Data submission rates remained patchy throughout phase I but improved in reach and consistency in phase II in response to financial incentives. Some evidence of improvement in clinical outcomes over time could be detected but was hard to interpret owing to variability in the denominators. CONCLUSIONS: These findings offer important lessons for large-scale improvement programmes, particularly when they seek to develop novel concepts and measures. External contexts may exert far-reaching influence. The challenges of developing measurement systems should not be underestimated. PMID- 27660318 TI - 25-year trends in gender disparity for obesity and overweight by using WHO and IOTF definitions among Chinese school-aged children: a multiple cross-sectional study. AB - OBJECTIVES: We sought to explore 25-year trends of gender disparity in the prevalence of obesity and overweight both in urban and rural areas among Chinese children from 1985 to 2010. METHODS: Data included 1 280 239 children aged 7-18 years enrolled in the Chinese National Survey on Students's Constitution and Health (CNSSCH), which is the largest nationally representative sample of school aged children in China. Obesity and overweight were defined according to both WHO and the International Obesity Task Force (IOTF) definitions. Logistic regression was used to estimate the prevalence OR (POR) of gender for obesity and overweight prevalence in different surveys. RESULTS: The prevalence of obesity increased (WHO definition: from 0.10% to 4.3%; IOTF definition: from 0.03% to 2.2%) over the past 25 years in urban and rural areas among Chinese children and it was much higher among boys than girls at each survey point (p<0.01). The increasing trend was significant in all age subgroups (p<0.01). Although the prevalence of obesity continuously increased in boys and girls, the changing pace was more rapid in boys than in girls. PORs of boys versus girls for obesity also increased over time, and the estimates of PORs were higher in urban areas than in rural areas at each survey point. CONCLUSIONS: The gradually increasing gender disparity in urban and rural areas suggests that the prevalence of obesity and overweight in boys, and especially in urban boys, contributes to a large and growing proportion of obese and overweight children. PMID- 27660319 TI - Potentially avoidable and ambulatory care sensitive hospitalisations among forced migrants: a protocol for a systematic review and meta-analysis. AB - INTRODUCTION: There is an increasing number of forced migrants globally, including refugees, asylum seekers, internally displaced persons and undocumented migrants. According to international law, forced migrants should enjoy access to health services free of discrimination equivalent to the host population, but they face barriers to healthcare worldwide. This may lead to a delay in care and result in preventable hospital treatment, referred to as potentially preventable hospitalisation (PPH) or ambulatory care sensitive hospitalisation (ACSH). There is as yet no overview of the prevalence of PPH in different countries and groups of forced migrants, and it is unknown whether the concept has been used among these migrant groups. We aim to systematically review the evidence (1) on the prevalence of PPH among forced migrants and (2) on differences in the prevalence of PPH between forced migrants and the general host population. METHODS AND ANALYSIS: A systematic review will be conducted searching databases (PubMed/MEDLINE, Web of Science/Knowledge, Cochrane Library, CINAHL, Google Scholar) and the internet (Google). INCLUSION CRITERIA: observational studies on forced migrants reporting PPH or ACSH with or without comparison groups published in the English or German language. EXCLUSION CRITERIA: studies on general migrant groups or hospitalisations without clear reference to avoidability. STUDY SELECTION: titles, abstracts and full texts will be screened in duplicate for eligibility. Data on the prevalence of PPH/ACSH among forced migrants, as well as any reported prevalence differences between host populations, will be systematically extracted. Quality appraisal will be performed using standardised checklists. The evidence will be synthesised in tabular form and by means of forest plots. A meta-analysis will be performed only among homogeneous studies (in terms of design and population). ETHICS AND DISSEMINATION: Ethical clearance is not necessary (secondary research). The results will be disseminated via publication in open access journals, conferences and public media. PROSPERO REGISTRATION NUMBER: CRD42016037081. PMID- 27660320 TI - Experiences of primary care professionals providing healthcare to recently arrived migrants: a qualitative study. AB - OBJECTIVES: The main objectives of the study were to explore the experiences of primary care professionals providing care to recent migrants in a superdiverse city and to elicit barriers and facilitators to meeting migrants' care needs. This paper focuses on a strong emergent theme: participants' descriptions and understandings of creating a fit between patients and practices. DESIGN: An exploratory, qualitative study based on the thematic analysis of semistructured interviews. SETTING AND PARTICIPANTS: A purposive sample of 10 practices. We interviewed 6 general practitioners, 5 nurses and 6 administrative staff; those based at the same practice opted to be interviewed together. 10 interviewees were from an ethnic minority background; some discussed their own experiences of migration. RESULTS: Creating a fit between patients and practice was complex and could be problematic. Some participants defined this in a positive way (reaching out, creating rapport) while others also focused on ways in which patients did not fit in, for example, different expectations or lack of medical records. A small but vocal minority put the responsibility to fit in on to migrant patients. Some participants believed that practice staff and patients sharing a language could contribute to achieving a fit but others outlined the disadvantages of over reliance on language concordance. A clearly articulated, team-based strategy to create bridges between practice and patients was often seen as preferable. CONCLUSIONS: Although participants agreed that a fit between patients and practice was desirable, some aimed to adapt to the needs of recently arrived migrants, while others thought that it was the responsibility of migrants to adapt to practice needs; a few viewed migrant patients as a burden to the system. Practices wishing to improve fit might consider developing strategies such as introducing link workers and other 'bridging' people; however, they could also aim to foster a general stance of openness to diversity. PMID- 27660322 TI - Prescriber preferences for behavioural economics interventions to improve treatment of acute respiratory infections: a discrete choice experiment. AB - OBJECTIVE: To elicit prescribers' preferences for behavioural economics interventions designed to reduce inappropriate antibiotic prescribing, and compare these to actual behaviour. DESIGN: Discrete choice experiment (DCE). SETTING: 47 primary care centres in Boston and Los Angeles. PARTICIPANTS: 234 primary care providers, with an average 20 years of practice. MAIN OUTCOMES AND MEASURES: Results of a behavioural economic intervention trial were compared to prescribers' stated preferences for the same interventions relative to monetary and time rewards for improved prescribing outcomes. In the randomised controlled trial (RCT) component, the 3 computerised prescription order entry-triggered interventions studied included: Suggested Alternatives (SA), an alert that populated non-antibiotic treatment options if an inappropriate antibiotic was prescribed; Accountable Justifications (JA), which prompted the prescriber to enter a justification for an inappropriately prescribed antibiotic that would then be documented in the patient's chart; and Peer Comparison (PC), an email periodically sent to each prescriber comparing his/her antibiotic prescribing rate with those who had the lowest rates of inappropriate antibiotic prescribing. A DCE study component was administered to determine whether prescribers felt SA, JA, PC, pay-for-performance or additional clinic time would most effectively reduce their inappropriate antibiotic prescribing. Willingness-to-pay (WTP) was calculated for each intervention. RESULTS: In the RCT, PC and JA were found to be the most effective interventions to reduce inappropriate antibiotic prescribing, whereas SA was not significantly different from controls. In the DCE however, regardless of treatment intervention received during the RCT, prescribers overwhelmingly preferred SA, followed by PC, then JA. WTP estimates indicated that each intervention would be significantly cheaper to implement than pay-for performance incentives of $200/month. CONCLUSIONS: Prescribing behaviour and stated preferences are not concordant, suggesting that relying on stated preferences alone to inform intervention design may eliminate effective interventions. TRIAL REGISTRATION NUMBER: NCT01454947; Results. PMID- 27660323 TI - Safety and efficacy of tranexamic acid in bleeding paediatric trauma patients: a systematic review protocol. AB - INTRODUCTION: Trauma is the leading cause of death among children aged 1-18. Studies indicate that better control of bleeding could potentially prevent 10-20% of trauma-related deaths. The antifibrinolytic agent tranexamic acid (TxA) has shown promise in haemorrhage control in adult trauma patients. However, information on the potential benefits of TxA in children remains sparse. This review proposes to evaluate the current uses, benefits and adverse effects of TxA in the bleeding paediatric trauma population. METHODS AND ANALYSIS: A structured search of bibliographic databases (eg, MEDLINE, EMBASE, PubMed, CINAHL, Cochrane CENTRAL) has been undertaken to retrieve randomised controlled trials and cohort studies that describe the use of TxA in paediatric trauma patients. To ensure that all relevant data were captured, the search did not contain any restrictions on language or publication time. After deduplication, citations will be screened independently by 2 authors, and selected for inclusion based on prespecified criteria. Data extraction and risk of bias assessment will be performed independently and in duplicate. Meta-analytic methods will be employed wherever appropriate. ETHICS AND DISSEMINATION: This study will not involve primary data collection, and formal ethical approval will therefore not be required. The findings of this study will be disseminated through a peer-reviewed publication and at relevant conference meetings. TRIAL REGISTRATION NUMBER: CRD42016038023. PMID- 27660321 TI - Bluebelle study (phase A): a mixed-methods feasibility study to inform an RCT of surgical wound dressing strategies. AB - OBJECTIVES: Dressing primary surgical wounds is common, but the implications for surgical site infection (SSI) remain unknown. The Bluebelle study aimed to determine the feasibility of a randomised controlled trial (RCT) comparing 'simple', 'complex' or 'no' dressings on abdominal wounds, as prespecified in a funder's research brief. Bluebelle includes exploratory work (phase A) to inform a pilot version of the proposed RCT (phase B). Phase A aimed to investigate current dressing practices and perspectives on the proposed RCT, with a view to refining the forthcoming pilot. DESIGN: Mixed methods, including semi-structured interviews and document analysis. SETTING: 6 UK hospitals. PARTICIPANTS: 51 patients and 92 clinical professionals from abdominal surgical specialities. RESULTS: Professionals had variable interpretations of what constitutes a 'dressing', particularly with respect to 'glue'-a product listed under 'wound closure products' in the British National Formulary, which some surgeons reportedly applied as a 'wound covering'. Areas of ambiguity arising from interviews informed development of pragmatic definitions, including specification of conditions under which glue constituted a 'dressing'. Professionals reported that 'simple' dressings were routinely used in practice, whereas 'complex' dressings were not. This raised questions about the relevance of comparison groups, prompting the design of a survey to determine the types/frequency of dressing use in abdominal surgery (reported elsewhere). This confirmed that complex dressings were rarely used, while 'glue as a dressing' was used relatively frequently. 'Complex dressings' were therefore substituted for 'glue as a dressing' (following an updated Cochrane review, which found insufficient evidence to determine the effectiveness of 'glue as a dressing'). Patients and professionals acknowledged uncertainty around dressing use and SSI prevention, but felt dressings may serve practical and/or psychological benefits. This steered development of additional outcome measures for the pilot. CONCLUSIONS: Pre-trial qualitative research can highlight areas of ambiguity and inform new lines of enquiry in relation to prespecified research briefs, enabling adjustments to RCT design that enhance relevance to practice. PMID- 27660326 TI - A link between planar polarity and staircase-like bundle architecture in hair cells. AB - Sensory perception in the inner ear relies on the hair bundle, the highly polarized brush of movement detectors that crowns hair cells. We previously showed that, in the mouse cochlea, the edge of the forming bundle is defined by the 'bare zone', a microvilli-free sub-region of apical membrane specified by the Insc-LGN-Galphai protein complex. We now report that LGN and Galphai also occupy the very tip of stereocilia that directly abut the bare zone. We demonstrate that LGN and Galphai are both essential for promoting the elongation and differential identity of stereocilia across rows. Interestingly, we also reveal that total LGN Galphai protein amounts are actively balanced between the bare zone and stereocilia tips, suggesting that early planar asymmetry of protein enrichment at the bare zone confers adjacent stereocilia their tallest identity. We propose that LGN and Galphai participate in a long-inferred signal that originates outside the bundle to model its staircase-like architecture, a property that is essential for direction sensitivity to mechanical deflection and hearing. PMID- 27660324 TI - Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal. AB - Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation. Tamoxifen-induced inactivation of Sox2 demonstrates the requirement of Sox2 for maintenance of the DESCs in adult mice. Conditional overexpression of Lef-1 in mice increases DESC proliferation and creates a new labial cervical loop stem cell compartment, which produces rapidly growing long tusk-like incisors, and Lef-1 epithelial overexpression partially rescues the tooth arrest in Sox2 conditional knockout mice. Mechanistically, Pitx2 and Sox2 interact physically and regulate Lef-1, Pitx2 and Sox2 expression during development. Thus, we have uncovered a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates DESC homeostasis and dental development. PMID- 27660328 TI - Medical Marijuana: Just the Beginning of a Long, Strange Trip? AB - Medical marijuana continues to gain acceptance and become legalized in many states. Various species of the marijuana plant have been cultivated, and this plant can contain up to 100 active compounds known as cannabinoids. Two cannabinoids seem the most clinically relevant: Delta9-tetrahydrocannabinol (THC), which tends to produce the psychotropic effects commonly associated with marijuana, and cannabidiol (CBD), which may produce therapeutic effects without appreciable psychoactive properties. Smoking marijuana, or ingesting extracts from the whole plant orally (in baked goods, teas, and so forth), introduces variable amounts of THC, CBD, and other minor cannabinoids into the systemic circulation, where they ultimately reach the central and peripheral nervous systems. Alternatively, products containing THC, CBD, or a combination of both compounds, can be ingested as oral tablets or via sprays applied to the oral mucosal membranes. These products may provide a more predictable method for delivering a known amount of specific cannabinoids into the body. Although there is still a need for randomized controlled trials, preliminary studies have suggested that medical marijuana and related cannabinoids may be beneficial in treating people with chronic pain, inflammation, spasticity, and other conditions seen commonly in physical therapist practice. Physical therapists, therefore, should be aware of the options that are available for patients considering medical marijuana and should be ready to provide information for these patients. Clinicians also should be aware that marijuana can produce untoward effects on cognition, coordination, balance, and cardiovascular and pulmonary function and should be vigilant for any problems that may arise if patients are using cannabinoids during physical rehabilitation. PMID- 27660327 TI - Monitoring cell-cell contacts in vivo in transgenic animals. AB - We used a synthetic genetic system based on ligand-induced intramembrane proteolysis to monitor cell-cell contacts in animals. Upon ligand-receptor interaction in sites of cell-cell contact, the transmembrane domain of an engineered receptor is cleaved by intramembrane proteolysis and releases a protein fragment that regulates transcription in the interacting partners. We demonstrate that the system can be used to regulate gene expression between interacting cells, both in vitro and in vivo, in transgenic Drosophila We show that the system allows for detection of interactions between neurons and glia in the Drosophila nervous system. In addition, we observed that when the ligand is expressed in subsets of neurons with a restricted localization in the brain it leads to activation of transcription in a selected set of glial cells that interact with those neurons. This system will be useful to monitor cell-cell interactions in animals, and can be used to genetically manipulate cells that interact with one another. PMID- 27660329 TI - Transcutaneous periorbital electrical stimulation in the treatment of dry eye. AB - PURPOSE: To evaluate efficacy and safety of transcutaneous application of electrical current on symptoms and clinical signs of dry eye (DE). METHODS: 27 patients with DE underwent transcutaneous electrostimulation with electrodes placed onto the periorbital region of both eyes and manual stimulation with a hand-piece conductor moved by the operator. Each patient underwent 12 sessions of 22 min spread over 2 months, two sessions per week in the first month and one session per week in the second month. Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), fluorescein staining of the cornea, Schirmer I test and adverse events were evaluated at baseline, at end of treatment and at 6 and 12 months. RESULTS: OSDI improved from 43.0+/-19.2 at baseline to 25.3+/-22.1 at end of treatment (mean+/-SD, p=0.001). These effects were substantially maintained at 6-month and 12-month follow-up evaluations. Improvement of the values of TBUT was recorded for the right eye at the end of treatment (p=0.003) and found in the left eye after 12 months (p=0.02). The Oxford scores changed in both eyes at the end of treatment and at the 6-month evaluation (p<0.001), and in the right eye at the 12-month evaluation (p=0.035). Schirmer I improved significantly at the end of treatment in the left eye (p=0.001) and in both eyes at the 12-month evaluation (p=0.004 and p=0.039 for the left and right eye, respectively). A significant reduction of the use of tear substitutes was found at the end of treatment (p=0.003), and was maintained during the follow-up (p<0.001).No complications occurred and patients found the treatment satisfying. CONCLUSIONS: Transcutaneous electrical stimulation was shown to improve DE, both subjectively and objectively, without any adverse effects and has the potential to enlarge the armamentarium for treating DE. PMID- 27660325 TI - Tankyrase inhibition promotes a stable human naive pluripotent state with improved functionality. AB - The derivation and maintenance of human pluripotent stem cells (hPSCs) in stable naive pluripotent states has a wide impact in human developmental biology. However, hPSCs are unstable in classical naive mouse embryonic stem cell (ESC) WNT and MEK/ERK signal inhibition (2i) culture. We show that a broad repertoire of conventional hESC and transgene-independent human induced pluripotent stem cell (hiPSC) lines could be reverted to stable human preimplantation inner cell mass (ICM)-like naive states with only WNT, MEK/ERK, and tankyrase inhibition (LIF-3i). LIF-3i-reverted hPSCs retained normal karyotypes and genomic imprints, and attained defining mouse ESC-like functional features, including high clonal self-renewal, independence from MEK/ERK signaling, dependence on JAK/STAT3 and BMP4 signaling, and naive-specific transcriptional and epigenetic configurations. Tankyrase inhibition promoted a stable acquisition of a human preimplantation ICM like ground state via modulation of WNT signaling, and was most efficacious in efficiently reprogrammed conventional hiPSCs. Importantly, naive reversion of a broad repertoire of conventional hiPSCs reduced lineage-primed gene expression and significantly improved their multilineage differentiation capacities. Stable naive hPSCs with reduced genetic variability and improved functional pluripotency will have great utility in regenerative medicine and human disease modeling. PMID- 27660330 TI - Optimising keratoplasty for Peters' anomaly in infants using spectral-domain optical coherence tomography. AB - PURPOSE: To present in vivo anterior segment optical coherence tomography (OCT) features of infants with Peters' anomaly obtained during presurgical examination under general anaesthesia, and to evaluate the impact of OCT features on surgical decision making. METHODS: This is a single-centre, consecutive, observational case series including 44 eyes of 27 infants with Peters' anomaly (5-18 months) undergoing keratoplasty. Medical records of patients were reviewed retrospectively. Clinical features and OCT findings, along with their impact on surgical decision-making were analysed. RESULTS: Of 27 patients, 10 had unilateral and 17 had bilateral disease. Two patients with mild disease (three eyes) had a posterior corneal defect with leukoma (2/27, 7.4%). Twenty patients (32 eyes) with iridocorneal adhesions were classified as having moderate Peters' anomaly (20/27, 74.1%) and five patients (nine eyes) with lenticulocorneal adhesions were classified as having severe Peters' anomaly (5/27, 18.5%). The range of angle closure, anterior chamber depth and maximum iridocorneal adhesion length (all p<0.001) were significantly different among groups, indicating that they might serve as novel OCT parameters for assessing the severity of Peters' anomaly. The surgical approach in seven patients (21.2%) was altered in response to intraoperative OCT findings, which provided information regarding the anatomical structure of the anterior chamber not provided by the surgical microscope. The use of OCT prevented unnecessary cataract surgeries in five patients. CONCLUSIONS: Our study showed that information gained from OCT under anaesthesia allows surgeons to classify type and severity of Peters' anomaly and supports surgical decision making. PMID- 27660331 TI - Association of anticholinergic burden with adverse effects in older people with intellectual disabilities: an observational cross-sectional study. AB - BACKGROUND: No studies to date have investigated cumulative anticholinergic exposure and its effects in adults with intellectual disabilities. AIMS: To determine the cumulative exposure to anticholinergics and the factors associated with high exposure. METHOD: A modified Anticholinergic Cognitive Burden (ACB) scale score was calculated for a representative cohort of 736 people over 40 years old with intellectual disabilities, and associations with demographic and clinical factors assessed. RESULTS: Age over 65 years was associated with higher exposure (ACB 1-4 odds ratio (OR) = 3.28, 95% CI 1.49-7.28, ACB 5+ OR = 3.08, 95% CI 1.20-7.63), as was a mental health condition (ACB 1-4 OR = 9.79, 95% CI 5.63 17.02, ACB 5+ OR = 23.74, 95% CI 12.29-45.83). Daytime drowsiness was associated with higher ACB (P<0.001) and chronic constipation reported more frequently (26.6% ACB 5+ v. 7.5% ACB 0, P<0.001). CONCLUSIONS: Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation. PMID- 27660332 TI - Parents who are aware when they are overweight themselves are more likely to recognise this in their children. PMID- 27660333 TI - The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models: A meta-analysis. AB - OBJECTIVES: The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models. METHODS: A systematic literature search up to May 2015 was carried out using the PubMed, Ovid, EBM reviews, ISI Web of Science, EBSCO, CBM, CNKI databases with the term and boolean operators: statins and osteonecrosis in all fields. Risk ratio (RR), as the risk estimate of specific outcome, was calculated along with 95% confidence intervals (CI). The methodological quality of individual studies was assessed using a quantitative tool based on the updated Stroke Therapy Academic Industry Roundtable (STAIR) recommendations. RESULTS: A total of 11 eligible studies were included according to predetermined criteria. The pooled data demonstrated that animals with statin usage, either alone or combined with other treatments, were at a decreased risk of developing glucocorticoid-related osteonecrosis (RR = 2.06, 95% confidence interval (CI) 1.71 to 2.50). Moreover, subgroup analysis revealed that compared with statins alone, statins combined with other treatments significantly decreased the risk of osteonecrosis (RR = 1.23, 95% CI 1.02 to 1.47). However, we could find no significant risk difference for different gender, or for different time points. CONCLUSIONS: The present study suggests that statins combined with other treatments are efficient in preventing the development of glucocorticoid-related osteonecrosis in animals. These results might shed light on clinical practice when glucocorticoids are prescribed, and could be further investigated in high quality clinical trials.Cite this article: Z. Yang, H. Liu, D. Li, X. Xie, T. Qin, J. Ma, P. Kang. The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models: A meta-analysis. Bone Joint Res 2016;5:393-402. DOI: 10.1302/2046-3758.59.2000500. PMID- 27660334 TI - Porous tantalum biocomposites for osteochondral defect repair: A follow-up study in a sheep model. AB - OBJECTIVES: We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. MATERIALS AND METHODS: Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double stranded DNA (dsDNA) content) and histologically. RESULTS: At 16 weeks post operatively, histological scores amongst treatment groups were not statistically different (TMPG: overall 12.7, cartilage 8.6, bone 4.1; TM: overall 14.2, cartilage 9.5, bone 4.9; ED: overall 13.6, cartilage 9.1, bone 4.5). Metal scaffolds were incorporated into the surrounding bone, both in TM and TMPG. The sGAG yield was lower in the neo-cartilage regions compared with the articular cartilage (AC) controls (TMPG 20.8/AC 39.5, TM 25.6/AC 33.3, ED 32.2/AC 40.2 ug sGAG/1 mg respectively), with statistical significance being achieved for the TMPG group (p < 0.05). Hypercellularity of the neo-cartilage was found in TM and ED, as the dsDNA content was significantly higher (p < 0.05) compared with contralateral AC controls (TM 126.7/AC 71.1, ED 99.3/AC 62.8 ng dsDNA/1 mg). The highest type II collagen content was found in neo-cartilage after TM compared with TMPG and ED (TM 60%/TMPG 40%/ED 39%). Inter-treatment differences were not significant. CONCLUSIONS: TM is a highly suitable material for the reconstitution of osseous defects. TM enables excellent bony ingrowth and fast integration. However, combined with autologous periosteum, such a biocomposite failed to promote satisfactory neo-cartilage formation.Cite this article: E. H. Mrosek, H W. Chung, J. S. Fitzsimmons, S. W. O'Driscoll, G. G. Reinholz, J. C. Schagemann. Porous tantalum biocomposites for osteochondral defect repair: A follow-up study in a sheep model. Bone Joint J 2016;5:403-411. DOI: 10.1302/2046-3758.59.BJR-2016 0070.R1. PMID- 27660336 TI - Classic Spotlight: 16S rRNA Redefines Microbiology. PMID- 27660335 TI - Classic Spotlight: Bacteroides thetaiotaomicron, Starch Utilization, and the Birth of the Microbiome Era. PMID- 27660339 TI - Switching from Remicade(r) to Remsima(r) is well Tolerated and Feasible: A Prospective, Open-label Study. AB - Background and Aims: A biosimilar version of infliximab [CT-P13/Remsima(r)] recently entered the European market. The clinical data on its use in inflammatory bowel disease [IBD] are sparse, especially on switching from the originator Remicade(r). In this study, we aimed to prospectively investigate the feasibility, safety and immunogenicity of switching from Remicade to Remsima in a real-life IBD population. Methods: All adult patients who were treated with Remicade in the Department of Gastroenterology at Oslo University Hospital were switched to Remsima. The follow-up lasted for 6 months. In addition, a retrospective registration was performed with a start time of 6 months before switching drugs. The primary endpoints were [i] the proportion of patients remaining on medication 6 months after switching and [ii] adverse events during the 6 months after switching. The secondary endpoints included [i] disease activity scores [Harvey-Bradshaw Index and Partial Mayo Score], C-reactive protein, haemoglobin, faecal calprotectin, infliximab dose and interval, and p infliximab and [ii] the development of antidrug antibodies. Results: In total, 143 IBD patients were switched, 99 with Crohn's disease and 44 with ulcerative colitis. The large majority [97%] remained on the medication throughout follow up. A low number of adverse events were observed. No change in disease activity, C-reactive protein, haemoglobin, faecal calprotectin, infliximab dose and interval or p-infliximab was detected. Three patients developed new detectable antidrug antibodies. Conclusions: Switching from Remicade to Remsima was feasible and with few adverse events, including very limited antidrug antibody formation and loss of response. PMID- 27660340 TI - The Complexity of alpha E beta 7 Blockade in Inflammatory Bowel Diseases. AB - Monoclonal antibodies targeting integrins are emerging as new treatment option in inflammatory bowel diseases. Integrins are molecules involved in cell adhesion and signalling. After the successful introduction of anti-alpha4beta7, currently anti-beta7 is under evaluation in a phase three trial. Anti-beta7 blocks both alpha4beta7/MAdCAM-1 and alphaEbeta7/E-cadherin interaction, targeting both the homing to and the retention in the gut of potential pathological T cells. Since the physiological and potential pathological roles of immune cells expressing alphaEbeta7 are less distinct than of those expressing alpha4beta7, an overview of the current state of knowledge on alphaEbeta7 in mice and humans in both health and inflammatory bowel diseases is presented here, also addressing the potential consequences of anti-beta7 treatment. PMID- 27660343 TI - Head-to-head Comparative Studies: Challenges and Opportunities? PMID- 27660345 TI - Defra commits to 50 mg/kg target for antibiotic use in livestock. PMID- 27660349 TI - Racing greyhound regulations 'successful' but still needed, says Defra. PMID- 27660350 TI - Supporting rabies control in India. AB - Earlier this year, Tony Fooks and colleagues described how, under a laboratory twinning project run by the World Organisation for Animal Health (OIE), the UK's OIE Reference Laboratory for rabies, based at the APHA in Weybridge, had been working with the Changchun Veterinary Research Institute in the People's Republic of China to help the institute develop into an OIE Reference Laboratory itself (VR, March 5, 2016, vol 178, pp 231-232). Now, the APHA is taking part in a further three-year project to build rabies diagnosis capability in Bangalore, India, as he and his colleagues explain below. PMID- 27660353 TI - Working across Europe to improve donkey welfare. AB - The UK public and veterinary profession often think of the equine charity sector as dealing with issues directly related to the UK equine population - overproduction, rehoming, shelter and welfare. However, the Donkey Sanctuary, like many UK-based equine charities, also works in Europe and further afield to try to address a much broader range of issues, as Alex Thiemann and Andy Foxcroft explain. PMID- 27660354 TI - Alopecia in lambs associated with micronutrient-deficient milk replacer. AB - ? Alopecia associated with micronutrient deficiency in lambs fed milk replacer? Idiopathic necrotising enteritis in suckler calves? Mannheimia haemolytica abomasitis in a five-week-old calf? Increased diagnoses of nematodirosis in lambs? Enteric and spinal listeriosis in sheepThese are among matters discussed in the disease surveillance report for June 2016 from SAC Consulting: Veterinary Services (SAC C VS). PMID- 27660355 TI - Animal suffering and expert evidence. PMID- 27660342 TI - 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations. AB - This paper is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al JCC 2016]. PMID- 27660356 TI - Two EBLV-2 infected Daubenton's bats detected in the north of England. PMID- 27660341 TI - 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management. AB - This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016]. PMID- 27660365 TI - Appreciating the difference, making a difference. AB - Luis Sainz-Pardo didn't realise how different his experience of working as a vet in the UK was until he returned home to Spain, and subsequently travelled throughout Europe. Now, he uses his understanding of veterinary diversity to forge a varied, interesting and international career path within the profession. PMID- 27660357 TI - Radiation safety in equine practice. PMID- 27660367 TI - Infographic. Physical activity for early years. PMID- 27660368 TI - Impact of the Nordic hamstring and hip extension exercises on hamstring architecture and morphology: implications for injury prevention. AB - BACKGROUND: The architectural and morphological adaptations of the hamstrings in response to training with different exercises have not been explored. PURPOSE: To evaluate changes in biceps femoris long head (BFLH) fascicle length and hamstring muscle size following 10-weeks of Nordic hamstring exercise (NHE) or hip extension (HE) training. METHODS: 30 recreationally active male athletes (age, 22.0+/-3.6 years; height, 180.4+/-7 cm; weight, 80.8+/-11.1 kg) were allocated to 1 of 3 groups: (1) HE training (n=10), NHE training (n=10), or no training (control, CON) (n=10). BFLH fascicle length was assessed before, during (Week 5) and after the intervention with a two-dimensional ultrasound. Hamstring muscle size was determined before and after training via MRI. RESULTS: Compared with baseline, BFLH fascicles were lengthened in the NHE and HE groups at mid-training (d=1.12-1.39, p<0.001) and post-training (d=1.77-2.17, p<0.001) and these changes did not differ significantly between exercises (d=0.49-0.80, p=0.279-0.976). BFLH volume increased more for the HE than the NHE (d=1.03, p=0.037) and CON (d=2.24, p<0.001) groups. Compared with the CON group, both exercises induced significant increases in semitendinosus volume (d=2.16-2.50, <=0.002) and these increases were not significantly different (d=0.69, p=0.239). CONCLUSION: NHE and HE training both stimulate significant increases in BFLH fascicle length; however, HE training may be more effective for promoting hypertrophy in the BFLH. PMID- 27660369 TI - AMSSM Position Statement on Cardiovascular Preparticipation Screening in Athletes: Current evidence, knowledge gaps, recommendations and future directions. AB - Cardiovascular screening in young athletes is widely recommended and routinely performed prior to participation in competitive sports. While there is general agreement that early detection of cardiac conditions at risk for sudden cardiac arrest and death (SCA/D) is an important objective, the optimal strategy for cardiovascular screening in athletes remains an issue of considerable debate. At the centre of the controversy is the addition of a resting ECG to the standard preparticipation evaluation using history and physical examination. The American Medical Society for Sports Medicine (AMSSM) formed a task force to address the current evidence and knowledge gaps regarding preparticipation cardiovascular screening in athletes from the perspective of a primary care sports medicine physician. The absence of definitive outcome-based evidence at this time precludes AMSSM from endorsing any single or universal cardiovascular screening strategy for all athletes, including legislative mandates. This statement presents a new paradigm to assist the individual physician in assessing the most appropriate cardiovascular screening strategy unique to their athlete population, community needs and resources. The decision to implement a cardiovascular screening programme, with or without the addition of ECG, necessitates careful consideration of the risk of SCA/D in the targeted population and the availability of cardiology resources and infrastructure. Importantly, it is the individual physician's assessment in the context of an emerging evidence base that the chosen model for early detection of cardiac disorders in the specific population provides greater benefit than harm. AMSSM is committed to advancing evidenced-based research and educational initiatives that will validate and promote the most efficacious strategies to foster safe sport participation and reduce SCA/D in athletes. PMID- 27660370 TI - Dupuytren disease is highly prevalent in male field hockey players aged over 60 years. AB - BACKGROUND/AIM: Dupuytren disease is a fibroproliferative hand condition. The role of exposure to vibration as a risk factor has been studied with contradictory results. Since field hockey is expected to be a strong source of hand-arm vibration, we hypothesised that long-term exposure to field hockey is associated with Dupuytren disease. METHODS: In this cross-sectional cohort study, the hands of 169 male field hockey players (IQR: 65-71 years) and 156 male controls (IQR: 59-71 years) were examined for signs of Dupuytren disease. Details about their age, lifestyle factors, medical history, employment history and leisure activities were gathered. Prior to the analyses, the groups were balanced in risk factors using propensity score matching. The association between field hockey and Dupuytren disease was determined using a subject-specific generalised linear mixed model with a binomial distribution and logit link function (matched pairs analysis). RESULTS: Dupuytren disease was observed in 51.7% of the field hockey players, and in 13.8% of the controls. After propensity score matching, field hockey playing as dichotomous variable, was associated with Dupuytren disease (OR=9.42, 95% CI 3.01 to 29.53). A linear dose-response effect of field hockey (hours/week x years) within the field hockey players could not be demonstrated (OR=1.03, 95% CI 0.68 to 1.56). DISCUSSION: We found that field hockey playing has a strong association with the presence of Dupuytren disease. Clinicians in sports medicine should be alert to this less common diagnosis in this sport. PMID- 27660371 TI - Infographic: How to maximise your golf performance. PMID- 27660372 TI - Investigation of the Intrinsic Spatial Resolution of an Intensified EMCCD Scintillation Camera. AB - In this paper, we present an experimental and Monte Carlo investigation of the intrinsic spatial resolution that can be achieved with the intensified electron multiplying charge-coupled device (I-EMCCD) gamma camera [1]-[4]. This detector has a very low readout noise, an ultra-high spatial resolution and a large active area of ~ 80 mm diameter, which is well-suited for small animal imaging applications. The intrinsic detector resolutions achieved with different scintillators and under different experimental conditions were compared. In this study, the simple centroiding method was compared with two model-fitting approaches for finding the locations of gamma ray interactions. The results from Monte Carlo simulation have demonstrated that with an appropriate detector configuration, it is possible to achieve an intrinsic resolution of ~ 30 um FWHM for detecting 27-35 keV gamma rays. The I-EMCCD scintillation camera offers a promising candidate for future ultra-high resolution SPECT imaging applications. PMID- 27660373 TI - Managing more than the mean: using quantile regression to identify factors related to large elk groups. AB - Animal group size distributions are often right-skewed, whereby most groups are small, but most individuals occur in larger groups that may also disproportionately affect ecology and policy. In this case, examining covariates associated with upper quantiles of the group size distribution could facilitate better understanding and management of large animal groups.We studied wintering elk groups in Wyoming, where group sizes span several orders of magnitude, and issues of disease, predation and property damage are affected by larger group sizes. We used quantile regression to evaluate relationships between the group size distribution and variables of land use, habitat, elk density and wolf abundance to identify conditions important to larger elk groups.We recorded 1263 groups ranging from 1 to 1952 elk and found that across all quantiles of group size, group sizes were larger in open habitat and on private land, but the largest effect occurred between irrigated and non-irrigated land [e.g. the 90th quantile group size increased by 135 elk (95% CI = 42, 227) on irrigation].Only upper quantile group sizes were positively related to broad-scale measures of elk density and wolf abundance. For wolf abundance, this effect was greater on elk groups found in open habitats and private land than those in closed habitats or public land. If we had limited our analysis to mean or median group sizes, we would not have detected these effects. Synthesis and applications. Our analysis of elk group size distributions using quantile regression suggests that private land, irrigation, open habitat, elk density and wolf abundance can affect large elk group sizes. Thus, to manage larger groups by removal or dispersal of individuals, we recommend incentivizing hunting on private land (particularly if irrigated) during the regular and late hunting seasons, promoting tolerance of wolves on private land (if elk aggregate in these areas to avoid wolves) and creating more winter range and varied habitats. Relationships to the variables of interest also differed by quantile, highlighting the importance of using quantile regression to examine response variables more completely to uncover relationships important to conservation and management. PMID- 27660374 TI - Surface-Anchored Poly(N-isopropylacrylamide) Orthogonal Gradient Networks. AB - We present a versatile synthetic route leading toward generating surface-attached polyacrylamide gels, in which the cross-link density varies continuously and gradually across the substrate in two orthogonal directions. We employ free radical polymerization to synthesize random copolymers comprising ~5% of photoactive methacrylyloxybenzophenone (MABP), ~5% of thermally active styrene sulfonyl azide (SSAz), and ~90% of N-isopropylacrylamide (NIPAAm) units. The presence of MABP and SSAz in the copolymer facilitates control over the cross link density of the gel in an orthogonal manner using photoactivated and thermally activated cross-linking chemistries, respectively. Spectroscopic ellipsometry is employed to determine the degree of swelling of the gel in water and methanol as a function of position on the substrate. Network swelling varies continuously and gradually across the substrate and is high in regions of low gel fractions and low in regions of high gel fractions. PMID- 27660376 TI - A fast method for optical simulation of flood maps of light-sharing detector modules. AB - Optical simulation of the detector module level is highly desired for Position Emission Tomography (PET) system design. Commonly used simulation toolkits such as GATE are not efficient in the optical simulation of detector modules with complicated light-sharing configurations, where a vast amount of photons need to be tracked. We present a fast approach based on a simplified specular reflectance model and a structured light-tracking algorithm to speed up the photon tracking in detector modules constructed with polished finish and specular reflector materials. We simulated conventional block detector designs with different slotted light guide patterns using the new approach and compared the outcomes with those from GATE simulations. While the two approaches generated comparable flood maps, the new approach was more than 200-600 times faster. The new approach has also been validated by constructing a prototype detector and comparing the simulated flood map with the experimental flood map. The experimental flood map has nearly uniformly distributed spots similar to those in the simulated flood map. In conclusion, the new approach provides a fast and reliable simulation tool for assisting in the development of light-sharing-based detector modules with a polished surface finish and using specular reflector materials. PMID- 27660375 TI - Impact of Comorbid Depressive Disorders on Subjective and Physiological Responses to Emotion in Generalized Anxiety Disorder. AB - Generalized anxiety disorder (GAD) and unipolar depressive disorders (UDD) have been shown to differ from each other in dimensions of affective functioning despite their high rates of comorbidity. We showed emotional film clips to a community sample (n = 170) with GAD, GAD with secondary UDD, or no diagnosis. Groups had comparable subjective responses to the clips, but the GAD group had significantly lower heart rate variability (HRV) during fear and after sadness, compared to controls. While HRV in the GAD and control groups rose in response to the sadness and happiness clips, it returned to baseline levels afterwards in the GAD group, potentially indicating lesser ability to sustain attention on emotional stimuli. HRV in the GAD + UDD group changed only in response to sadness, but was otherwise unvarying between timepoints. Though preliminary, these findings suggest comorbid UDD as a potential moderator of emotional responding in GAD. PMID- 27660377 TI - Massive hydropneumopericardium after pericardial drain removal. PMID- 27660379 TI - Heart failure with preserved ejection fraction: blame the veins.... PMID- 27660378 TI - Influenza vaccination and risk of hospitalization in patients with heart failure: a self-controlled case series study. AB - Aims: Evidence supporting yearly influenza vaccination in patients with chronic heart failure (HF) is limited, consequently leading to inconsistent guideline recommendations. We aimed to investigate the impact of influenza vaccination on the risk of hospitalization in HF patients. Methods and results: We used linked primary and secondary health records in England between 1990 and 2013. Using a self-controlled case series design with conditional Poisson regression, we estimated the incidence rate ratio (IRR, 95% CI) of the number of hospitalizations in a year following vaccination with an adjacent vaccination free year in the same individuals. We found the uptake of vaccination to be varied and generally low (49% in 2013). Among 59,202 HF patients, influenza vaccination was associated with a lower risk of hospitalization due to cardiovascular disease (0.73 [0.71, 0.76]), with more modest effects for hospitalization due to respiratory infections (0.83 [0.77, 0.90]), and all-cause hospitalizations (0.96 [0.95, 0.98]). The relative effects were somewhat greater in younger patients but with no material difference between men and women. In validation analyses, effects were not significant for consecutive years without vaccination (0.96 [0.92, 1.00]) or hospitalization due to cancer (1.02 [0.84, 1.22]). Conclusion: In HF patients, influenza vaccination is associated with reduced risk of hospitalizations, especially for cardiovascular disease. Improved efforts for wider uptake of vaccination among HF patients are needed. PMID- 27660380 TI - Percutaneous revascularization of concurrently obstructed left-sided pulmonary veins complicating catheter ablation for atrial fibrillation. PMID- 27660381 TI - Repetitive vasospasm as a cause of plaque rupture and myocardial infarction. PMID- 27660382 TI - Combining Population and Patient-Specific Characteristics for Prostate Segmentation on 3D CT Images. AB - Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy. PMID- 27660383 TI - Random Walk Based Segmentation for the Prostate on 3D Transrectal Ultrasound Images. AB - This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem. Our segmentation algorithm is initialized with the user roughly marking the prostate and non-prostate points on the mid-gland slice which are fitted into an ellipse for obtaining more points. Based on these fitted seed points, we run the random walk algorithm to segment the prostate on the mid-gland slice. The segmented contour and the information from the decision tree classification are combined to determine the initial seed points for the other slices. The random walk algorithm is then used to segment the prostate on the adjacent slice. We propagate the process until all slices are segmented. The segmentation method was tested in 32 3D transrectal ultrasound images. Manual segmentation by a radiologist serves as the gold standard for the validation. The experimental results show that the proposed method achieved a Dice similarity coefficient of 91.37+/-0.05%. The segmentation method can be applied to 3D ultrasound-guided prostate biopsy and other applications. PMID- 27660384 TI - Determining Cardiac Fiber Orientation Using FSL and Registered Ultrasound/DTI volumes. AB - Accurate extraction of cardiac fiber orientation from diffusion tensor imaging is important for determining heart structure and function. However, the acquisition of magnetic resonance (MR) diffusion tensor images is costly and time consuming. By comparison, cardiac ultrasound imaging is rapid and relatively inexpensive, but it lacks the capability to directly measure fiber orientations. In order to create a detailed heart model from ultrasound data, a three-dimensional (3D) diffusion tensor imaging (DTI) with known fiber orientations can be registered to an ultrasound volume through a geometric mask. After registration, the cardiac orientations from the template DTI can be mapped to the heart using a deformable transformation field. This process depends heavily on accurate fiber orientation extraction from the DTI. In this study, we use the FMRIB Software Library (FSL) to determine cardiac fiber orientations in diffusion weighted images. For the registration between ultrasound and MRI volumes, we achieved an average Dice similarity coefficient (DSC) of 81.6+/-2.1%. For the estimation of fiber orientations from the proposed method, we achieved an acute angle error (AAE) of 22.7+/-3.1 degrees as compared to the direct measurements from DTI. This work provides a new approach to generate cardiac fiber orientation that may be used for many cardiac applications. PMID- 27660385 TI - Multiplatform Biomarker Discovery for Bladder Cancer Recurrence Diagnosis. AB - Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence. A multiplatform strategy was used for marker quantification comprising a multiplexed microarray and an automated platform for ELISA analysis. A multivariate statistical analysis combined the results from both platforms with the collected clinical data. Results. The best performing combination of biomarkers and clinical parameters achieved an AUC value of 0.91, showing better performance than individual parameters. This panel comprises six biomarkers (cadherin-1, IL-8, ErbB2, IL-6, EN2, and VEGF-A) and three clinical parameters (number of past recurrences, number of BCG therapies, and stage at time of diagnosis). Conclusions. The multiparameter panel could be a useful noninvasive tool for BCa surveillance and potentially impact the clinical management of this disease. Validation of results in an independent cohort is warranted. PMID- 27660386 TI - Factors influencing time to computed tomography in emergency department patients with suspected subarachnoid haemorrhage. AB - BACKGROUND: CT has excellent sensitivity for subarachnoid haemorrhage (SAH) when performed within 6 hours of headache onset, but it is unknown to what extent patients with more severe disease are likely to undergo earlier CT, potentially inflating estimates of sensitivity. Our objective was to evaluate which patient and hospital factors were associated with earlier neuroimaging in alert, neurologically intact ED patients with suspected SAH. METHODS: We analysed data from two large sequential prospective cohorts of ED patients with acute headache undergoing CT for suspected SAH. We examined the time interval from headache onset to CT, both overall and subdivided from headache onset to hospital registration and from registration to CT. RESULTS: Among 2412 patients with headache, 194 had SAH, with 178 identified on unenhanced CT. Of these, 91 (51.1%) were identified by CT within 6 hours of headache onset and 87 after 6 hours. Patients with SAH had a shorter time from headache onset to hospital presentation (median 4.5 hours, IQR 1.7-22.7 vs 9.6 hours, IQR 2.8-46.0, p<0.001) and were imaged sooner after headache onset (6.4 hours, IQR 3.5-27.1 vs 12.6 hours, IQR 5.5-48.0, p<0.001) compared with those without SAH. The median time from in hospital registration to CT scan was significantly shorter in those patients with SAH although this difference was less than 1 hour (1.9 hours, IQR 1.2-2.8 vs 2.5 hours, IQR 1.5-3.9, p<0.001). Arrival by ambulance (OR 3.1, 95% CI 1.94 to 4.98, p<0.001) and higher acuity at triage (OR 1.39, 95% CI 1.02 to 1.88, p=0.032) were among the factors associated with having CT imaging within 6 hours of headache onset. CONCLUSIONS: Time from headache onset to imaging is moderately associated with positive imaging for SAH. Delay to hospital presentation accounts for the largest fraction of time to imaging, especially those without SAH. These findings suggest limited opportunity to reduce lumbar puncture rates simply by accelerating in-hospital processes when imaging delays are under 2 hours, as diagnostic yield of imaging decreases beyond the 6-hour imaging window from headache onset. PMID- 27660387 TI - Calmodulin Gates Aquaporin 0 Permeability through a Positively Charged Cytoplasmic Loop. AB - Aquaporin 0 (AQP0), the major intrinsic protein of the eye lens, plays a vital role in maintaining lens clarity by facilitating the transport of water across lens fiber cell membranes. AQP0 reduces its osmotic water permeability constant (Pf) in response to increases in the external calcium concentration, an effect that is mediated by an interaction with the calcium-binding messenger protein, calmodulin (CaM), and phosphorylation of the CaM-binding site abolishes calcium sensitivity. Despite recent structural characterization of the AQP0-CaM complex, the mechanism by which CaM modulates AQP0 remains poorly understood. By combining atomistic molecular dynamics simulations and oocyte permeability assays, we conclude that serine phosphorylation of AQP0 does not inhibit CaM binding to the whole AQP0 protein. Instead, AQP0 phosphorylation alters calcium sensitivity by modifying the AQP0-CaM interaction interface, particularly at an arginine-rich loop that connects the fourth and fifth transmembrane helices. This previously unexplored loop, which sits outside of the canonical CaM-binding site on the AQP0 cytosolic face, mechanically couples CaM to the pore-gating residues of the second constriction site. We show that this allosteric loop is vital for CaM regulation of the channels, facilitating cooperativity between adjacent subunits and regulating factors such as serine phosphorylation. Similar allosteric interactions may also mediate CaM modulation of the properties of other CaM regulated proteins. PMID- 27660389 TI - The Signaling Pathway of Caenorhabditis elegans Mediates Chemotaxis Response to the Attractant 2-Heptanone in a Trojan Horse-like Pathogenesis. AB - The nematode Caenorhabditis elegans exhibits behavioral responses to a wide range of odorants associated with food and pathogens. A previous study described a Trojan Horse-like strategy of pathogenesis whereby the bacterium Bacillus nematocida B16 emits the volatile organic compound 2-heptanone to trap C. elegans for successful infection. Here, we further explored the receptor for 2-heptanone as well as the pathway involved in signal transduction in C. elegans Our experiments showed that 2-heptanone sensing depended on the function of AWC neurons and a GPCR encoded by str-2 Consistent with the above observation, the HEK293 cells expressing STR-2 on their surfaces showed a transient elevation in intracellular Ca2+ levels after 2-heptanone applications. After combining the assays of RNA interference and gene mutants, we also identified the Galpha subunits and their downstream components in the olfactory signal cascade that are necessary for responding to 2-heptanone, including Galpha subunits of egl-30 and gpa-3, phospholipase C of plc-1and egl-8, and the calcium channel of cmk-1 and cal-1. Our work demonstrates for the first time that an integrated signaling pathway for 2-heptanone response in C. elegans involves recognition by GPCR STR 2, activation by Galpha subunits of egl-30/gpa-3 and transfer to the PLC pathway, indicating that a potentially novel olfactory pathway exists in AWC neurons. Meanwhile, since 2-heptanone, a metabolite from the pathogenic bacterium B. nematocida B16, can be sensed by C. elegans and thus strongly attract its host, our current work also suggested coevolution between the pathogenic microorganism and the chemosensory system in C. elegans. PMID- 27660388 TI - Functional Analysis of gamma-Tubulin Complex Proteins Indicates Specific Lateral Association via Their N-terminal Domains. AB - Microtubules are nucleated from multiprotein complexes containing gamma-tubulin and associated gamma-tubulin complex proteins (GCPs). Small complexes (gammaTuSCs) comprise two molecules of gamma-tubulin bound to the C-terminal domains of GCP2 and GCP3. gammaTuSCs associate laterally into helical structures, providing a structural template for microtubule nucleation. In most eukaryotes gammaTuSCs associate with additional GCPs (4, 5, and 6) to form the core of the so-called gamma-tubulin ring complex (gammaTuRC). GCPs 2-6 constitute a family of homologous proteins. Previous structural analysis and modeling of GCPs suggest that all family members can potentially integrate into the helical structure. Here we provide experimental evidence for this model. Using chimeric proteins in which the N- and C-terminal domains of different GCPs are swapped, we show that the N-terminal domains define the functional identity of GCPs, whereas the C terminal domains are exchangeable. FLIM-FRET experiments indicate that GCP4 and GCP5 associate laterally within the complex, and their interaction is mediated by their N-terminal domains as previously shown for gammaTuSCs. Our results suggest that all GCPs are incorporated into the helix via lateral interactions between their N-terminal domains, whereas the C-terminal domains mediate longitudinal interactions with gamma-tubulin. Moreover, we show that binding to gamma-tubulin is not essential for integrating into the helical complex. PMID- 27660390 TI - Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8 Dihydro-8-oxoguanine. AB - Numerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols kappa and eta in vitro The primer extension reaction catalyzed by human replicative pol alpha was strongly blocked by 8-oxo-rG. pol kappa inefficiently bypassed rG and 8-oxo-rG compared with dG and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG), whereas pol eta easily bypassed the ribonucleotides. pol alpha exclusively inserted dAMP opposite 8-oxo-rG. Interestingly, pol kappa preferentially inserted dCMP opposite 8-oxo-rG, whereas the insertion of dAMP was favored opposite 8-oxo-dG. In addition, pol eta accurately bypassed 8-oxo-rG. Furthermore, we examined the activity of the base excision repair (BER) enzymes 8 oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease 1 on the substrates, including rG and 8-oxo-rG. Both BER enzymes were completely inactive against 8-oxo-rG in DNA. However, OGG1 suppressed 8-oxo-rG excision by RNase H2, which is involved in the removal of ribonucleotides from DNA. These results suggest that the different sugar backbones between 8-oxo-rG and 8-oxo-dG alter the capacity of TLS and repair of 8-oxoguanine. PMID- 27660391 TI - TCL/RhoJ Plasma Membrane Localization and Nucleotide Exchange Is Coordinately Regulated by Amino Acids within the N Terminus and a Distal Loop Region. AB - TCL/RhoJ is a Cdc42-related Rho GTPase with reported activities in endothelial cell biology and angiogenesis, metastatic melanoma, and corneal epithelial cells; however, less is known about how it is inherently regulated in comparison to its closest homologues TC10 and Cdc42. TCL has an N-terminal extension of 18 amino acids in comparison to Cdc42, but the function of this amino acid sequence has not been elucidated. A truncation mutant lacking the N terminus (DeltaN) was found to alter TCL plasma membrane localization and nucleotide binding, and additional truncation and point mutants mapped the alterations of TCL biochemistry to amino acids 17-20. Interestingly, whereas the TCL DeltaN mutant clearly influenced nucleotide exchange, deletion of the N terminus from its closest homologue, TC10, did not have a similar effect. Chimeras of TCL and TC10 revealed amino acids 121-129 of TCL contributed to the differences in nucleotide loading. Together, these results identify amino acids within the N terminus and a loop region distal to the nucleotide binding pocket of TCL capable of allosterically regulating nucleotide exchange and thus influence membrane association of the protein. PMID- 27660392 TI - Glutathione Depletion, Pentose Phosphate Pathway Activation, and Hemolysis in Erythrocytes Protecting Cancer Cells from Vitamin C-induced Oxidative Stress. AB - The discovery that oxidized vitamin C, dehydroascorbate (DHA), can induce oxidative stress and cell death in cancer cells has rekindled interest in the use of high dose vitamin C (VC) as a cancer therapy. However, high dose VC has shown limited efficacy in clinical trials, possibly due to the decreased bioavailability of oral VC. Because human erythrocytes express high levels of Glut1, take up DHA, and reduce it to VC, we tested how erythrocytes might impact high dose VC therapies. Cancer cells are protected from VC-mediated cell death when co-cultured with physiologically relevant numbers of erythrocytes. Pharmacological doses of VC induce oxidative stress, GSH depletion, and increased glucose flux through the oxidative pentose phosphate pathway (PPP) in erythrocytes. Incubation of erythrocytes with VC induced hemolysis, which was exacerbated in erythrocytes from glucose-6-phosphate dehydrogenase (G6PD) patients and rescued by antioxidants. Thus, erythrocytes protect cancer cells from VC-induced oxidative stress and undergo hemolysis in vitro, despite activation of the PPP. These results have implications on the use of high dose VC in ongoing clinical trials and highlight the importance of the PPP in the response to oxidative stress. PMID- 27660395 TI - The Structure of Oral Language and Reading and Their Relation to Comprehension in Kindergarten through Grade 2. AB - This study examined the structure of oral language and reading and their relation to comprehension from a latent variable modeling perspective in Kindergarten, Grade 1, and Grade 2. Participants were students in Kindergarten (n = 218), Grade 1 (n = 372), and Grade 2 (n = 273), attending Title 1 schools. Students were administered phonological awareness, syntax, vocabulary, listening comprehension, and decoding fluency measures in mid-year. Outcome measures included a listening comprehension measure in Kindergarten and a reading comprehension test in Grades1 and 2. In Kindergarten, oral language (consisting of listening comprehension, syntax, and vocabulary) shared variance with phonological awareness in predicting a listening comprehension outcome. However, in Grades 1 and 2, phonological awareness was no longer predictive of reading comprehension when decoding fluency and oral language were included in the model. In Grades 1 and 2, oral language and decoding fluency were significant predictors of reading comprehension. PMID- 27660394 TI - Breaking out of biogeographical modules: range expansion and taxon cycles in the hyperdiverse ant genus Pheidole. AB - AIM: We sought to reconstruct the biogeographical structure and dynamics of a hyperdiverse ant genus, Pheidole, and to test several predictions of the taxon cycle hypothesis. Using large datasets on Pheidole geographical distributions and phylogeny, we (1) inferred patterns of biogeographical modularity (clusters of areas with similar faunal composition), (2) tested whether species in open habitats are more likely to be expanding their range beyond module boundaries, and (3) tested whether there is a bias of lineage flow from high- to low diversity areas. LOCATION: The Old World. METHODS: We compiled and jointly analysed a comprehensive database of Pheidole geographical distributions, the ecological affinities of different species, and a multilocus phylogeny of the Old World radiation. We used network modularity methods to infer biogeographical structure in the genus and comparative methods to evaluate the hypotheses. RESULTS: The network analysis identified eight biogeographical modules, and a suite of species with anomalous ranges that are statistically more likely to occur in open habitat, supporting the hypothesis that open habitats promote range expansion. Phylogenetic analysis shows evidence for a cascade pattern of colonization from Asia to New Guinea to the Pacific, but no 'upstream' colonization in the reverse direction. MAIN CONCLUSIONS: The distributions of Pheidole lineages in the Old World are highly modular, with modules generally corresponding to biogeographical regions inferred in other groups of organisms. However, some lineages have expanded their ranges across module boundaries, and these species are more likely to be adapted to open habitats rather than interior forest. In addition, there is a cascade pattern of dispersal from higher to lower diversity areas during these range expansions. Our findings are consistent with the taxon cycle hypothesis, although they do not rule out alternative interpretations. PMID- 27660397 TI - The Russian Orthodox Church as moral norm entrepreneur. AB - Conflicts over religious symbols in the public sphere, gay marriage, abortion or gender equality have shown their disruptive potential across many societies in the world. They have also become the subject of political and legal debates in international institutions. These conflicts emerge out of different worldviews and normative conceptions of the good, and they are frequently framed in terms of competing interpretations of human rights. One newcomer voice in conflicts over rights and values in the international sphere is the Russian Orthodox Church (ROC), which in recent years has become an active promoter of 'traditional values' both inside Russia and internationally. This article studies the ideational prerequisites and dynamics of Russian Orthodox 'norm protagonism' in the international arena. PMID- 27660396 TI - Stress Recovery Effects of High- and Low-Frequency Amplified Music on Heart Rate Variability. AB - Sounds can induce autonomic responses in listeners. However, the modulatory effect of specific frequency components of music is not fully understood. Here, we examined the role of the frequency component of music on autonomic responses. Specifically, we presented music that had been amplified in the high- or low frequency domains. Twelve healthy women listened to white noise, a stress inducing noise, and then one of three versions of a piece of music: original, low , or high-frequency amplified. To measure autonomic response, we calculated the high-frequency normalized unit (HFnu), low-frequency normalized unit, and the LF/HF ratio from the heart rate using electrocardiography. We defined the stress recovery ratio as the value obtained after participants listened to music following scratching noise, normalized by the value obtained after participants listened to white noise after the stress noise, in terms of the HFnu, low frequency normalized unit, LF/HF ratio, and heart rate. Results indicated that high-frequency amplified music had the highest HFnu of the three versions. The stress recovery ratio of HFnu under the high-frequency amplified stimulus was significantly larger than that under the low-frequency stimulus. Our results suggest that the high-frequency component of music plays a greater role in stress relief than low-frequency components. PMID- 27660393 TI - An Isozyme-specific Redox Switch in Human Brain Glycogen Phosphorylase Modulates Its Allosteric Activation by AMP. AB - Brain glycogen and its metabolism are increasingly recognized as major players in brain functions. Moreover, alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. In the brain, both muscle and brain glycogen phosphorylase isozymes regulate glycogen mobilization. However, given their distinct regulatory features, these two isozymes could confer distinct metabolic functions of glycogen in brain. Interestingly, recent proteomics studies have identified isozyme-specific reactive cysteine residues in brain glycogen phosphorylase (bGP). In this study, we show that the activity of human bGP is redox-regulated through the formation of a disulfide bond involving a highly reactive cysteine unique to the bGP isozyme. We found that this disulfide bond acts as a redox switch that precludes the allosteric activation of the enzyme by AMP without affecting its activation by phosphorylation. This unique regulatory feature of bGP sheds new light on the isoform-specific regulation of glycogen phosphorylase and glycogen metabolism. PMID- 27660398 TI - Attractor-Based Obstructions to Growth in Homogeneous Cyclic Boolean Automata. AB - We consider a synchronous Boolean organism consisting of N cells arranged in a circle, where each cell initially takes on an independently chosen Boolean value. During the lifetime of the organism, each cell updates its own value by responding to the presence (or absence) of diversity amongst its two neighbours' values. We show that if all cells eventually take a value of 0 (irrespective of their initial values) then the organism necessarily has a cell count that is a power of 2. In addition, the converse is also proved: if the number of cells in the organism is a proper power of 2, then no matter what the initial values of the cells are, eventually all cells take on a value of 0 and then cease to change further. We argue that such an absence of structure in the dynamical properties of the organism implies a lack of adaptiveness, and so is evolutionarily disadvantageous. It follows that as the organism doubles in size (say from m to 2m) it will necessarily encounter an intermediate size that is a proper power of 2, and suffers from low adaptiveness. Finally we show, through computational experiments, that one way an organism can grow to more than twice its size and still avoid passing through intermediate sizes that lack structural dynamics, is for the organism to depart from assumptions of homogeneity at the cellular level. PMID- 27660399 TI - Classroom Age Composition and Vocabulary Development Among At-Risk Preschoolers. AB - RESEARCH FINDINGS: The purpose of this exploratory study was to examine the relationship between classroom age composition and preschoolers' vocabulary gains over an academic year and also to examine whether these relations were moderated by classroom quality. In this study (N = 130 children in 16 classrooms representing a subset of all children enrolled in these classrooms), results showed a significant cross-level interaction between classroom age composition and children's age, suggesting positive effects of greater variance in classroom age composition for younger but not older children. The interaction between behavior management (1 dimension of classroom quality) and classroom age composition was also significant, indicating that a wider distribution of classroom age composition was positively related to children's vocabulary gains within classrooms characterized by better behavior management. PRACTICE OR POLICY: Findings underscore the importance of children's social interactions with more knowledgeable conversational partners in promoting their vocabulary development and signify the need to help teachers learn how to manage children's behaviors so as to provide a classroom that is optimal for child learning. PMID- 27660400 TI - How do individual-level sociodemographics and neighbourhood-level characteristics influence residential location behaviour in the context of the food and built environment? Findings from 25 years of follow-up in the CARDIA Study. AB - BACKGROUND: Little is known about how diet-related and activity-related amenities relate to residential location behaviour. Understanding these relationships is essential for addressing residential self-selection bias. METHODS: Using 25 years (6 examinations) of data from the Coronary Artery Risk Development in Young Adults (CARDIA) study (n=11 013 observations) and linked neighbourhood-level data from the 4 CARDIA baseline cities (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; Oakland, California, USA), we characterised participants' neighbourhoods as having low, average or high road connectivity and amenities using non-hierarchical cluster analysis. We then used repeated measures multinomial logistic regression with random effects to examine the associations between individual-level sociodemographics and neighbourhood-level characteristics with residential neighbourhood types over the 25-year period, and whether these associations differed by individual-level income. RESULTS: Being female was positively associated with living in neighbourhoods with low (vs high) road connectivity and activity-related and diet-related amenities among high income individuals only. At all income levels, a higher percentage of neighbourhood white population and neighbourhood population <18 years were associated with living in neighbourhoods with low (vs high) connectivity and amenities. Individual-level race; age; and educational attainment, neighbourhood socioeconomic status and housing prices did not influence residential location behaviour related to neighbourhood connectivity and amenities at any income level. CONCLUSIONS: Neighbourhood-level factors appeared to play a comparatively greater role in shaping residential location behaviour than individual-level sociodemographics. Our study is an important step in understanding how residential locational behaviour relates to amenities and physical activity opportunities, and may help mitigate residential self-selection bias in built environment studies. PMID- 27660401 TI - Prevalence and patterns of tobacco smoking among Chinese adult men and women: findings of the 2010 national smoking survey. AB - BACKGROUND: China consumes about 40% of the world's cigarettes, predominantly by men, following a large increase in recent decades. We assess sex-specific prevalence and changing patterns of smoking in Chinese adults in the current decade. METHODS: A nationally representative survey of smoking was conducted in 2010 among 100 000 Chinese adults aged >=18 years, using a multistage stratified cluster sampling method. Information on smoking frequency, type, amount, age started and quitting was collected. Sex-specific standardised prevalence and means were analysed and compared with estimates in the 1996 national survey. RESULTS: In Chinese men aged >=18, 62.4% were ever-smokers in 2010, including 54.0% current smokers and 8.4% ex-smokers. The smoking prevalence was higher in rural than in urban men (63.9% vs 58.4%). In younger men, the age to start smoking was earlier and exclusive cigarette use was much higher. Among current smokers, only 17.3% intended to quit. Compared with a similar survey in 1996 among adults aged 30-69, more smokers had quit in 2010 than in 1996 (11.0% vs 4.2%), but the number of cigarettes smoked per current smoker was higher (17.9 vs 15.2). In Chinese women, only 3.4% ever smoked and there has been a large intergenerational decrease in smoking uptake rates. In 2010, there were 318 million current smokers in China, consuming an estimated 1740 billion cigarettes. CONCLUSIONS: The prevalence of smoking remained extremely high in men, but low and falling in Chinese women. Tobacco smoking remains an important public health issue in China, and stronger and more efficient tobacco control is urgently needed. PMID- 27660403 TI - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features. AB - Recently, it was proposed that some papillary thyroid carcinomas (PTC) will no longer be termed 'cancer' and are christened as 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features' (NIFTP). As this is a recent definition, little information is available about NIFTP. The objective of this study was to report the frequency, ultrasonographic appearance, cytology result and long-term evolution of cases of NIFTP seen at our institution. We excluded tumours <=1 cm. The sample consisted of 129 patients. Sixty-four patients were submitted to total thyroidectomy and 65 to lobectomy. These patients with NIFTP did not receive radioiodine. NIFTP corresponded to 15% of cases diagnosed as PTC >1 cm. An ultrasonographic appearance considered to be of low suspicion for malignancy was common in NIFTP (32.5%), whereas a highly suspicious appearance was uncommon (5%). NIFTP frequently exhibited indeterminate cytology (62%), while malignant cytology was uncommon (4%). The patients were followed up for 12-146 months (median 72 months) after surgery. None of the patients developed structural disease during follow-up. Comparing the concentrations of thyroglobulin (Tg) and anti-Tg antibodies (TgAb) obtained 6-12 months after surgery and in the last assessment, none of the patients exhibited an increase in these markers. PMID- 27660402 TI - WOMEN IN CANCER THEMATIC REVIEW: Circadian rhythmicity and the influence of 'clock' genes on prostate cancer. AB - The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison with those working regular hours. The common finding in these 'high-risk' groups was that they all experienced a deregulation of the body's internal circadian rhythm. Here, we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression. Circadian rhythmicity of androgen production is lost in CaP patients, with the clock genes Per1 and Per2 decreasing, and Bmal1 increasing, in these individuals. Periodic expression of the clock genes was restored upon administration of the neurohormone melatonin, thereby suppressing CaP progression. Activation of the melatonin receptors and the AR antagonized each other, and therefore the tumour suppressive effects of melatonin and the clock genes were most clearly observed in the absence of androgens, that is, in conjunction with androgen deprivation therapy (ADT). In addition, a large-scale study found that high-dose radiation was more effective in CaP patients when it was delivered before 17:00 h, compared with those delivered after 17:00 h, suggesting that the therapy was more effective when delivered in synchrony with the patient's circadian clock. As CaP patients are shown to become easily resistant to new therapies, perhaps circadian delivery of these therapeutic agents or delivery in conjunction with melatonin and its novel analogs should be tested to see if they prevent this resistance. PMID- 27660405 TI - Development of Hollow-Fiber Liquid-Phase Microextraction Method for Determination of Urinary trans,trans-Muconic Acid as a Biomarker of Benzene Exposure. AB - For the first time, hollow-fiber liquid-phase microextraction combined with high performance liquid chromatography-ultraviolet was used to extract trans,trans muconic acid, in urine samples of workers who had been exposed to benzene. The parameters affecting the metabolite extraction were optimized as follows: the volume of sample solution was 11 mL with pH 2, liquid membrane containing dihexyl ether as the supporter, 15% (w/v) of trioctylphosphine oxide as the carrier, the time of extraction was 120 minutes, and stirring rate was 500 rpm. Organic phase impregnated in the pores of a hollow fiber was extracted into 24 uL solution of 0.05 mol L(-1) Na2CO3 located inside the lumen of the fiber. Under optimized conditions, a high enrichment factor of 153-182 folds, relative recovery of 83% 92%, and detection limit of 0.001 ug mL(-1) were obtained. The method was successfully applied to the analysis of ttMA in real urine samples. PMID- 27660406 TI - Effects and Safety of Linagliptin as an Add-on Therapy in Advanced-Stage Diabetic Nephropathy Patients Taking Renin-Angiotensin-Aldosterone System Blockers. AB - BACKGROUND: We investigated the effects and safety of linagliptin as an add-on therapy in patients with advanced-stage diabetic nephropathy (DMN) taking renin angiotensin-aldosterone system (RAAS) blockers. METHOD: Twenty advanced-stage DMN patients (estimated glomerular filtration rate (eGFR): 24.5 +/- 13.4 mL/min/1.73 m(2)) taking RAAS blockers were administered 5 mg/day linagliptin for 52 weeks. Changes in glucose and lipid metabolism and renal function were evaluated. RESULTS: Linagliptin decreased glycosylated hemoglobin levels (from 7.32 +/- 0.77% to 6.85 +/- 0.87%, P < 0.05) without changing fasting blood glucose levels, and significantly decreased total cholesterol levels (from 189.6 +/- 49.0 to 170.2 +/- 39.2 mg/dL, P < 0.05) and low-density lipoprotein cholesterol levels (from 107.1 +/- 32.4 to 90.2 +/- 31.0 mg/dL, P < 0.05) without changing high density lipoprotein cholesterol and triglyceride levels. Urine protein/creatinine ratio and annual change in eGFR remained unchanged. No adverse effects were observed. CONCLUSION: Linagliptin as an add-on therapy had beneficial effects on glucose and lipid metabolism without impairment of renal function, and did not have any adverse effects in this population of patients with advanced-stage DMN taking RAAS blockers. PMID- 27660407 TI - Pushed monocanalicular intubation versus probing as a primary management for congenital nasolacrimal obstruction. AB - PURPOSE: Evaluation of efficiency, complications, and advantages of pushed monocanalicular intubation using Masterka((r)) tube versus simple probing in patients with congenital nasolacrimal duct obstruction (CNLDO). PATIENTS AND METHODS: This is a case-controlled study that included 60 eyes (of 53 patients); 30 eyes underwent probing and 30 eyes intubation using the Masterka tube as a primary treatment for CNLDO. The children were aged between 6 months and 36 months at the time of surgery, with no previous nasolacrimal surgical procedure, and had one or more of the following clinical signs of nasolacrimal duct obstruction: epiphora, mucous discharge, and/or increased tear lake. RESULTS: We defined success by absence of epiphora, mucous discharge, or increased tear lake 1 month after tube removal. The overall success rate in the probing group was 80%, while it was 83.3% in the intubation group. CONCLUSION: Pushed monocanalicular intubation is an effective method for treatment of CNLDO; it requires only mask inhalation anesthesia and could be considered as an appropriate alternative procedure with imperceptible complications. PMID- 27660408 TI - Patients' tolerance of bimanual lid retraction versus a metal speculum for intravitreal injections. AB - OBJECTIVE: To compare patients' acceptance of and correlate their pain level for bimanual versus metal speculum fixation in intravitreal injections. DESIGN: Prospective analysis. PARTICIPANTS: Seventy-three eyes of 56 patients. METHODS: A questionnaire indicating patients' discomfort and pain grading immediately after intravitreal injections using either bimanual fixation or metal speculum fixation (Barraquer Wire Speculum). RESULTS: Fifty-six patients who underwent intravitreal injections were enrolled in this study for various conditions. Patients' overall pain and discomfort were as follows, right eye - bimanual was 0.3 on our grading scale with a standard deviation of 0.54, right eye - metal was 1.6 on our grading scale with a standard deviation of 1.5, left eye - bimanual was 0.41 on our grading scale with a standard deviation of 0.87, and left eye - metal was 1.91 on our grading scale with a standard deviation of 1.14 (P=0.003). CONCLUSION: Patients who underwent bimanual fixation had a much more comfortable experience with less pain in comparison to patients who underwent metal speculum fixation. PMID- 27660404 TI - Single-Molecule Tracking and Its Application in Biomolecular Binding Detection. AB - In the past two decades significant advances have been made in single-molecule detection, which enables the direct observation of single biomolecules at work in real time and under physiological conditions. In particular, the development of single-molecule tracking (SMT) microscopy allows us to monitor the motion paths of individual biomolecules in living systems, unveiling the localization dynamics and transport modalities of the biomolecules that support the development of life. Beyond the capabilities of traditional camera-based tracking techniques, state-of-the-art SMT microscopies developed in recent years can record fluorescence lifetime while tracking a single molecule in the 3D space. This multiparameter detection capability can open the door to a wide range of investigations at the cellular or tissue level, including identification of molecular interaction hotspots and characterization of association/dissociation kinetics between molecules. In this review, we discuss various SMT techniques developed to date, with an emphasis on our recent development of the next generation 3D tracking system that not only achieves ultrahigh spatiotemporal resolution but also provides sufficient working depth suitable for live animal imaging. We also discuss the challenges that current SMT techniques are facing and the potential strategies to tackle those challenges. PMID- 27660409 TI - Update on corticosteroids for diabetic macular edema. AB - Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME. PMID- 27660410 TI - Visual outcome after emergency surgery for open globe eye injury in Japan. AB - BACKGROUND: Most patients with open globe eye injury are brought to hospital as emergency patients and usually require admission for emergency surgery. We analyzed the visual outcome in patients with open globe eye injury at our hospital over a 4-year period. PATIENTS AND METHODS: This study reviewed 40 eyes of 40 patients with open globe eye injury who were presented to Juntendo University Shizuoka Hospital and required emergency surgery during the 4 years from January 2010 to December 2014. Retrospective evaluation of the visual outcome was performed using data from the medical records, including assessment of the influence of sex, side of the eye injury, cause of injury, and site/severity of injury. RESULTS: The mean age (SD) at the time of the injury was 58.9 years (+/-25.1 years). There were 28 males (70.0%) and 12 females (30.0%). Statistically significant improvement in visual acuity after treatment was noted in the males (P=0.0015, Wilcoxon test), but not in the females. Twenty-five patients had injury to the right eye (62.5%) and 15 had injury to the left eye (37.5%). A significant improvement in visual acuity was achieved after treatment of injury to the right eye (P=0.021), but not the left eye (P=0.109). The most frequent cause of injury was an accident (15 eyes; 37.5%). The second most frequent cause was work-related injury (14 eyes; 35.0%), which only occurred in males, and the third cause was accident due to negligence (eleven eyes; 27.5%). Two patients developed sympathetic ophthalmia and one patient developed postoperative endophthalmitis. CONCLUSION: The majority of patients with open globe eye injury were male workers in Japan. The visual outcome of work-related injury was better than that of injury due to other causes. The visual outcome was also better if the right eye was injured compared with the left eye. Patients with injuries due to negligence were older than the other groups, and this finding might be characteristic of an aging society. PMID- 27660411 TI - The use of misoprostol for cervical priming prior to hysteroscopy: a systematic review and analysis. AB - The effects of misoprostol use on cervical priming prior to hysteroscopy have been controversial. Therefore, a systematic literature review and meta-analysis of studies were conducted to assess the effect of misoprostol on cervical priming prior to hysteroscopy. All studies published before July 2014 with data related to the use of misoprostol for cervical priming compared with placebo or no medication prior to hysteroscopy, were identified. Twenty-five randomized controlled trials involving 2,203 females were systematically analyzed. The results showed that, compared with placebo or no medication, the use of misoprostol prior to hysteroscopy led to a significant relief of the need for cervical dilatation, resulted in a significantly greater cervical width, had fewer hysteroscopy complications, and mild and insignificant side effects. Subgroup analyses revealed that the regimen of 200 or 400 MUg vaginal misoprostol may be a simple and effective method for cervical priming, especially prior to operative hysteroscopy. PMID- 27660413 TI - Preparation of novel pirfenidone microspheres for lung-targeted delivery: in vitro and in vivo study. AB - The aim of this study was to develop and characterize pirfenidone (PF)-loaded chitosan microspheres for lung targeting. The microspheres were prepared using the emulsion-solvent evaporation method and characterized by assessing morphology, particle size, and zeta potential. The microspheres had a spherical nature with highly smooth and integrated surfaces. The particle size of microspheres was 4.6+/-0.3 um, and the zeta potential was 20.3+/-1.4 mV. The in vitro release results indicated that the obtained formulation of PF could reach the state of sustained release with a biphasic drug release pattern. It was observed that there was no significant difference in both the percentage of entrapment efficiency and that of drug release before and after the stability study. In vivo, the calculated relative bioavailability indicated greater pulmonary absorption of PF when it was encapsulated in microspheres. According to histopathological studies, no histological change occurred to the rat lung after the administration of PF-loaded chitosan microspheres. PMID- 27660412 TI - Intranasal administration of elastin-like polypeptide for therapeutic delivery to the central nervous system. AB - Bypassing the blood-brain barrier is one of the primary considerations when designing compounds intended to function in the central nervous system (CNS). Intranasal (IN) administration of otherwise blood-brain barrier impermeable molecules can result in high CNS concentrations and low systemic accumulation, indicating that IN administration may be a useful method of delivering therapeutics to the CNS. Elastin-like polypeptide (ELP) is a large, non immunogenic, highly manipulable biopolymer with extensive evidence supporting its use as a carrier with the ability to improve drug pharmacokinetics and drug targeting. The ability of ELP to reach the CNS via IN administration has been shown previously. Previous studies have also identified the ability of cell penetrating peptides (CPPs) to increase the uptake of molecules in some instances, including via the IN route. Here, we compared and contrasted the biodistribution of ELPs with or without addition of the CPPs Tat or SynB1 via both the IN and intravenous routes. Administration of ELP via the IN route led to significant accumulation in the brain, especially in the olfactory bulbs. When injected intravenously, <3% of the ELP signal was present outside the vascular compartment. This contrasted with IN administration, which resulted in 79% of the fluorescence signal localized outside the vascular space. The fusion of Tat or SynB1 significantly altered the biodistribution of ELP, decreasing the total CNS accumulation following IN administration. The addition of CPPs to ELP increased their retention in the nasal epithelium. These results suggest ELP may represent an effective CNS delivery vector without further modification and that the addition of a CPP significantly influences biodistribution. PMID- 27660414 TI - Development and in vitro characterization of poly(lactide-co-glycolide) microspheres loaded with an antibacterial natural drug for the treatment of long term bacterial infections. AB - Biodegradable polymers, especially poly(lactide-co-glycolide) (PLGA), have good biocompatibility and toxicological properties. In combination with active ingredients, a specialized drug delivery system can be generated. The aim of the present study was to develop a drug delivery system consisting of PLGA microspheres loaded with the natural active ingredient totarol, which has several antimicrobial mechanisms. Totarol, isolated from the Podocarpus totara tree, was purified using column chromatography, and the eluate was checked for purity using thin layer chromatography. The spherically shaped microspheres with mean diameters of 147.21+/-3.45 um and 131.14+/-3.69 um (totarol-loaded and -unloaded microspheres, respectively) were created using the single emulsion evaporation method. Furthermore, the encapsulation efficiency, in a range of 84.72%+/-6.68% to 92.36%+/-0.99%, was measured via UV/vis spectroscopy. In a 90-day in vitro drug release study, the release of totarol was investigated by UV/vis spectroscopy as well, showing a release of 53.76%. The toxicity on cells was determined using BJ fibroblasts or Human Embryonic Kidney cells and an 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, which showed no influence on the cell growth. The minimal inhibitory concentration was ascertained. A totarol concentration between 64 ug/mL and 128 ug/mL was necessary to inhibit the bacterial growth over a period of 24 hours. Biofilm formation on the surface of totarol-loaded microspheres was determined using transmission electron microscopy. No biofilm formation could be detected, even if the totarol concentration was below the minimal inhibitory concentration. The hemocompatibility investigations on various markers with fresh heparinized blood (1.5 IU/mL) showed that totarol and totarol-loaded microspheres have no influence on different blood parameters. The PLGA microspheres characterized by slow release of totarol and great entrapment efficiency represent a novel drug delivery system, which may be highly beneficial for the long-term therapy of bacterial infections. PMID- 27660415 TI - Downregulation of DOCK1 sensitizes bladder cancer cells to cisplatin through preventing epithelial-mesenchymal transition. AB - During the past several decades, resistance to single or multiple anticancer agents has posed a great challenge in cancer therapy. Dedicator of cytokinesis 1 (DOCK1), the first identified member in DOCK family, plays diverse roles in cellular processes, including tumorigenesis. In this study, we explored the biological role of DOCK1 in the chemotherapeutic resistance in bladder cancer and its underlying mechanism. Our results showed that the bladder cancer cell lines UM-UC-3 and J82 with higher DOCK1 are more resistant to cisplatin, whereas B87 cells with the lowest expression of DOCK1 exhibited the highest sensitivity to cisplatin. Down-regulation of DOCK1 with small interfering RNA (siRNA) increased the cisplatin sensitivity in bladder cancer cells. Moreover, treatment with cisplatin induced epithelial-mesenchymal transition (EMT), while transfection with Twist siRNA restored the chemosensitivity to cisplatin. In addition, we found that downregulation of DOCK1 reversed EMT program in bladder cancer cells. However, cotransfection with DOCK1 siRNA could not further enhance the cisplatin sensitivity and cellular phenotypic changes in tumor cells. Taken together, these results demonstrate that downregulation of DOCK1 could increase the chemosensitivity in bladder cancer cells via preventing cisplatin-induced EMT, suggesting that DOCK1 may serve as a potential therapeutic target in bladder cancer. PMID- 27660416 TI - In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer. AB - In situ administration of 5-fluorouracil (5FU) "thermosensitive" gel effectively reduced systemic side effects in treating colon rectal cancer; however, the penetration efficacy of the formulation was considerably low due to the poor lipid solubility of 5FU. The aim of this study was to develop thermosensitive gel mediated 5FU water-in-oil microemulsion (TG-5FU-ME) for improving the infiltration of 5FU. An in vitro release test showed that TG-5FU-ME sustained the drug's release up to 10 hours. TG-5FU-ME exhibited good stability, and the microemulsion entrapped did not show any change in morphology and 5FU content during the 4-month storage. Transportation test in the Caco-2 cell monolayer showed that TG-5FU-ME had a permeability 6.3 times higher than that of 5FU thermosensitive gel, and the intracellular uptake of 5FU increased by 5.4-fold compared to that of 5FU thermosensitive gel. In vivo tissue distribution analysis exhibited that the TG-5FU-ME group had drug levels in rectal tissue and mesenteric lymph nodes, which were significantly higher than those of 5FU thermosensitive gel group, with very low blood levels of 5FU in both groups. Furthermore, TG-5FU-ME was not associated with detectable morphological damage to the rectal tissue. Conclusively, TG-5FU-ME might be an efficient rectal delivery system to treat colorectal cancer. PMID- 27660417 TI - Acceptability of an intelligent wireless sensor system for the rapid detection of health issues: findings among home-dwelling older adults and their informal caregivers. AB - BACKGROUND: Aging at home rather than in an institution is now considered the gold standard. Public health figures document an important demographic transition to an increasingly elderly society. At the same time, this is accompanied by the emergence of significant numbers of innovative technologies to help and support home-dwelling older adults in declining health who wish to remain at home. STUDY AIM: To explore the acceptability of intelligent wireless sensor system (IWSS) among home-dwelling older adults in rapidly detecting their health issues. METHODS: Data were sourced from a pilot 3-month randomized clinical trial that involved 34 older patients in the experimental group (EG) using an IWSS to rapidly detect falls and other health issues at home. The effectiveness of the IWSS was assessed by comparing it to participants' functional and cognitive status, as measured both before and after the trial. The Resident Assessment Instrument for Home Care, Confusion Assessment Method, Cognitive Performance Scale, Geriatric Depression Scale, and Informed Questionnaire on Cognitive Decline in the Elderly were used for the assessments. Acceptability of the IWSS was explored at the end of the study. RESULTS: Both older adults and their informal caregivers considered the performance and usefulness of the IWSS intervention to be low to moderate. A majority of the participants were unsatisfied with its ease of use and found multiple obstacles in using and having an intention to use the IWSS. However, their informal caregivers were more satisfied with the program and gave higher scores for usefulness, ease of use, and intention to use IWSS technology. CONCLUSION: The IWSS displayed low-to moderate acceptability among the older participants and their informal caregivers. We recommend improving and clarifying several components in the IWSS for the development of a design that is user-centered. PMID- 27660418 TI - Erratum: Association between patients' beliefs and oral antidiabetic medication adherence in a Chinese type 2 diabetic population [Corrigendum]. AB - [This corrects the article on p. 1161 in vol. 10, PMID: 27390519.]. PMID- 27660419 TI - Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema. AB - OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient's life; a score of 0.0 reflects death and 1.0 reflects full health. STUDY DESIGN AND METHODS: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5 Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. RESULTS: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. CONCLUSION: The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts. PMID- 27660420 TI - Impact of Ramadan focused education program on hypoglycemic risk and metabolic control for patients with type 2 diabetes. AB - BACKGROUND: Fasting during the month of Ramadan could lead to acute complications and increased hypoglycemic risk of patients with type 2 diabetes. Therefore, diabetes is one of the diseases that need careful observation and special considerations during Ramadan including patients' education and counseling. OBJECTIVES: To evaluate the impact of Ramadan focused education program on acute complications and biomedical parameters. METHODS: A prospective nonrandomized interventional controlled design was run on three phases: before, during, and after Ramadan on 262 type 2 diabetes patients. The intervention group (n=140) received focused individualized diabetic education sessions and antidiabetic medications adjustment before and after Ramadan, while the control group (n=122) received standard diabetic care. A validated hypoglycemia questionnaire was used in both groups to assess the change of the risk. Patients were advised to adjust the dosage and timing of antidiabetic agents according to the recommendations for management of diabetes during Ramadan. Primary outcomes were postintervention change of hypoglycemia score and HbA1c over 6-month follow-up. Data were presented as mean +/- standard deviation. HbA1c was expressed in percentage. RESULTS: The hypoglycemic scores before, during, and after Ramadan were 14.21+/ 8.50, 6.36+/-6.17, and 5.44+/-5.55 in the intervention group, respectively (P<0.001) and 14.01+/-5.10, 13.46+/-5.30, and 9.27+/-4.65 in the control group, respectively (P<0.001). HbA1c levels were 9.79+/-1.89, 8.26+/-1.54, and 8.52+/ 1.61 before, during, and after Ramadan in the intervention group, respectively (P<0.001), and 10.04+/-1.47, 9.54+/-1.38, and 9.59+/-1.79 in the control group, respectively (P<0.001). Post-Ramadan reductions of HbA1c and hypoglycemic scores were significantly higher in the intervention group (-13.0% vs -4.5%, P=0.004 for HbA1c and -61.7% vs -33.8%, P<0.001 for hypoglycemic score). Low-density lipoprotein cholesterol improved in the intervention group from 2.41+/-0.91 mmol/L before Ramadan to 2.28+/-0.68 mmol/L after Ramadan (P<0.001). No statistically significant effects were observed on blood pressure or body weight in the intervention group. Also, no change was observed in the control group. CONCLUSION: Ramadan educational program had a positive impact with reduction of hypoglycemic risk, HbA1c, and low-density lipoprotein cholesterol. Therefore, it could be recommended for patients with increased risk of hypoglycemia during Ramadan fasting. PMID- 27660421 TI - Chilean patients' perception of oral health-related quality of life after third molar surgery. AB - OBJECTIVE: To describe the perception of the quality of life in oral health based on the Health-Related Quality of Life instrument in its Spanish version (HRQOL sp) in Chilean patients with third molar extraction surgery. PATIENTS AND METHODS: A cross-sectional study. The HRQOL-sp was administered to dental patients at the Public Hospital in Rio Bueno in southern Chile treated for unilateral third molar extraction between March and June 2014. The instrument was applied by phone survey on the first, third, fifth, and seventh days after surgery. For the ordinal scale, the response was considered interference in the quality of life when patients selected the options "quite a bit of trouble" or "lots of trouble" for oral function and general activity; and selected complications-related signs and symptoms, a pain level score with a Verbal Rating Scale (range 0 to 7), and worst pain perceived. The patient's sociodemographic data, type of surgery, and the quality of life level were analyzed according to the domains of the HRQOL-sp instrument. RESULTS: A total of 106 patients were selected (age: 20.4+/-7.39 years; 71.7% women) and a total of 127 extracted third molars. On the first day of follow-up, most patients reported interference in their quality of life. The main problems were difficulty opening the mouth (50.94%) and swelling (83.02%). The worst symptom perceived was "bad breath" (>31%) and the worst pain felt was a mean of 4.31+/-1.62 on the Verbal Rating Scale. All items gradually reduced until the seventh day. CONCLUSION: The HRQOL sp revealed substantial interference in the quality of life on the first postoperative day. It is suggested that the risk factors associated with quality of life be analyzed and the instrument in Spanish be validated. PMID- 27660422 TI - Self-administered C1 esterase inhibitor concentrates for the management of hereditary angioedema: usability and patient acceptance. AB - Hereditary angioedema (HAE) is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH). The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze((r)), Berinert((r)), and Cetor((r)); however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self administered or administered by a caregiver) is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE. PMID- 27660423 TI - A randomized, controlled trial to test the effectiveness of a glaucoma patient navigator to improve appointment adherence. AB - PURPOSE: Patients with glaucoma who do not keep their follow-up eye care appointments are at risk for developing more severe ocular disease. The primary aim of the current study was to evaluate whether the use of a patient navigator altered adherence to follow-up eye care appointments in community-versus office based settings. PATIENTS AND METHODS: Patients diagnosed with a glaucoma-related condition following a comprehensive eye examination at 43 community sites in Philadelphia, PA, USA, were enrolled in this prospective, randomized, controlled trial. Patients were randomized into three groups for a 1-year period: Group 1 (G1) received follow-up eye care in a community-based setting with assistance from a patient navigator; Group 2 (G2) received follow-up eye care in an office based setting with assistance from a patient navigator; and Group 3 (G3) received follow-up eye care in an office-based setting without a patient navigator (usual care). Adherence rates were compared among these three groups using a chi-squared test at a significance level of 0.05. RESULTS: A total of 155 patients with glaucoma-related diagnoses were enrolled. The mean age (+/-standard deviation) was 71.2 (+/-10.0) years. Patients were predominantly female (65.8%, n=102/155) and African-American (71.6%, n=111/155). The mean (+/-standard deviation) number of follow-up visits during the 1-year study period was 1.3 (+/-1.3) for G1, 1.6 (+/-1.3) for G2, and 1.3 (+/-1.1) for G3 (P=0.48). Appointment adherence, defined as attendance of >=1 follow-up visit, was 69.8% (n=37/53) for G1, 82.5% (n=47/57) for G2, and 73.3% (n=33/45) for G3, (P=0.28). Sub-analysis of adherence rates for patients who attended >=2 follow-up visits were 91.3% (n=21/23) for G1, 74.3% (n=26/35) for G2, and 66.7% (n=18/27) for G3, (P=0.11). CONCLUSION: Help from a patient navigator did not increase the likelihood of keeping >=1 follow-up appointment in an office-based setting. Adherence rates for follow-up appointments reached close to 70% or above in a self-selected patient population. PMID- 27660424 TI - Integrated Pest Management Practices Reduce Insecticide Applications, Preserve Beneficial Insects, and Decrease Pesticide Residues in Flue-Cured Tobacco Production. AB - Integrated pest management (IPM) recommendations, including scouting and economic thresholds (ETs), are available for North Carolina flue-cured tobacco growers, although ETs for key pests have not been updated in several decades. Moreover, reported IPM adoption rates by flue-cured tobacco growers remain low, at < 40%, according to NC cooperative extension surveys conducted during the last four years. Previous research has suggested that timing insecticide treatments using currently available ETs can reduce the average number of applications to two or fewer per season. We conducted field-scale trials at nine commercial tobacco farms, three in 2104 and six in 2015, to quantify inputs associated with current scouting recommendations, to determine if current ETs were able to reduce insecticide applications as compared to grower standard practices, and to assess the impacts of reduced insecticide applications on end of season yield and pesticide residues. Two fields were identified at each farm and were scouted weekly for insects. One field was only treated with insecticides if pests reached ET (IPM), while the other field was managed per grower discretion (Grower Standard). IPM fields received an average of two fewer insecticide applications without compromising yield. More insecticide applications resulted in higher pesticide residues in cured leaf samples from Grower Standard fields than those from IPM fields. Reductions in insecticides and management intensity also resulted in larger beneficial insect populations in IPM fields. PMID- 27660425 TI - Relative Tolerance of Six Bactrocera (Diptera: Tephritidae) Species to Phytosanitary Cold Treatment. AB - To compare relative cold treatment tolerance across the economically important tephritid fruit flies (Diptera: Tephritidae), Bactrocera carambolae Drew & Hancock, Bactrocera correcta (Bezzi), Bactrocera cucurbitae (Coquillett), four populations of Bactrocera dorsalis (Hendel), Bactrocera zonata (Saunders), and Bactrocera tryoni (Froggatt), eggs (in vitro), and larvae (in infested fruit or on carrot diet) were cold treated at 2.0 +/- 0.2 degrees C for selected durations. The study was performed to assess whether a single (i.e., generic) cold treatment could be developed that would control the entire group of fruit flies that were tested. Probit regression models showed that the hierarchy of cold resistance was third-instar larvae reared on carrot diet > third-instar larvae reared on orange > eggs test in vitro. Differences in mortality responses of third-instar larvae reared in oranges across populations of B. dorsalis were observed only at subefficacious levels of control. The majority of Bactrocera species responded the same at the high levels of control demanded of phytosanitary treatments, which indicated that cold treatments would be similarly effective across the species and populations tested. B. cucurbitae was found to be the most cold tolerant of all the species tested. PMID- 27660427 TI - Clinical effectiveness in severe knee osteoarthritis after intra-articular platelet-rich plasma therapy in association with hyaluronic acid injection: three case reports. AB - Osteoarthritis (OA) is a degenerative disorder resulting from loss of joint cartilage and underlying bone and causes pain and loss of function. The treatment of knee OA is still a challenge because of the poor self-regeneration capacity of cartilage. The nonsurgical interventions include control of the aggravating factor (such as weight control and the use of walking aids), symptomatic treatment (such as acetaminophen or nonsteroidal anti-inflammatory drugs), prolotherapy, and viscosupplementation. However, the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) has not been widely used because of lack of clinical evidence and several limitations in patients with severe knee OA. Three patients who suffered from knee pain and poor walking endurance were diagnosed with advanced knee OA. They underwent PRP treatment in association with intra articular HA injection and showed pain relief and functional improvement. The follow-up standard weight-bearing X-ray images of knees also confirmed the improvement and indicated the possibility of regeneration of the articular cartilage. These cases provide clinical and radiographic evidence for a new therapy for advanced knee OA. This treatment strategy of PRP in association with HA injection can offer a chance to treat severe knee OA, rather than immediate surgery, or a chance for those who cannot undergo surgery. It can also postpone the need of arthroplasty and can significantly improve the daily activity function. PMID- 27660426 TI - Sex differences in stroke: a socioeconomic perspective. AB - BACKGROUND: A number of studies have explored the issue of sex differences in stroke from biomedical perspective; however, there are still large gaps in the existing knowledge. The purpose of this study was to assess whether the differences in socioeconomic status and living conditions between men and women may explain the part of the sex differences in incidence and outcomes of stroke. METHODS: All stroke participants aged >=60 years admitted in Vaseie Hospital in Sabzevar, Iran, from March 21, 2013, until March 20, 2014, were included in this study. Computerized tomography and magnetic resonance imaging were used to confirm stroke. A series of chi2 tests were performed and Statistical Program for Social Sciences, Version 21.0, was used to investigate the potential differences between older men and women in stroke incidence and outcomes. RESULTS: A total of 159 incident stroke cases were documented during 1 year. The annual rate of stroke was statistically significantly higher in elderly women than in elderly men (401 vs 357 per 100,000; P<0.001). Female elderly participants had significantly lower socioeconomic status, poorer living conditions, and higher lifetime history of depression, hypertension, and diabetes mellitus than their male counterparts. CONCLUSION: The findings from this study showed that elderly women are more adversely affected by stroke in terms of incidence and outcomes of stroke than elderly men. The most noticeable result is that sex differences in socioeconomic status and living conditions may result in increased incidence of stroke and poorer outcomes in elderly women. Therefore, it is imperative to identify vulnerable elderly women and provide them appropriate treatment and services. PMID- 27660428 TI - Impact of tobacco smoking on cytokine signaling via interleukin-17A in the peripheral airways. AB - There is excessive accumulation of neutrophils in the airways in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms remain poorly understood. It is known that extracellular cytokine signaling via interleukin (IL)-17A contributes to neutrophil accumulation in the airways but nothing is known about the impact of tobacco smoking on extracellular signaling via IL-17A. Here, we characterized the impact of tobacco smoking on extracellular cytokine signaling via IL-17A in the peripheral airways in long-term smokers with and without COPD and in occasional smokers before and after short-term exposure to tobacco smoke. We quantified concentrations of IL-17A protein in cell-free bronchoalveolar lavage (BAL) fluid samples (Immuno-quantitative PCR) and cytotoxic T-cells (immunoreactivity for CD8+ and CD3+) in bronchial biopsies. Matrix metalloproteinase-8 and human beta defensin 2 proteins were also quantified (enzyme-linked immunosorbent assay) in the BAL samples. The concentrations of IL-17A in BAL fluid were higher in long-term smokers without COPD compared with nonsmoking healthy controls, whereas those with COPD did not differ significantly from either of the other groups. Short-term exposure to tobacco smoke did not induce sustained alterations in these concentrations in occasional smokers. Long-term smokers displayed higher concentrations of IL-17A than did occasional smokers. Moreover, these concentrations correlated with CD8+ and CD3+ cells in biopsies among long-term smokers with COPD. In healthy nonsmokers, BAL concentrations of matrix metalloproteinase-8 and IL-17A correlated, whereas this was not the case in the pooled group of long-term smokers with and without COPD. In contrast, BAL concentrations of human beta defensin 2 and IL-17A correlated in all study groups. This study implies that long-term but not short-term exposure to tobacco smoke increases extracellular cytokine signaling via IL-17A in the peripheral airways. In the smokers with COPD, this signaling may involve cytotoxic T-cells. Long-term exposure to tobacco smoke leads to a disturbed association of extracellular IL-17A signaling and matrix metalloproteinase-8, of potential importance for the coordination of antibacterial activity. PMID- 27660430 TI - Application of the homology method for quantification of low-attenuation lung region inpatients with and without COPD. AB - BACKGROUND: Homology is a mathematical concept that can be used to quantify degree of contact. Recently, image processing with the homology method has been proposed. In this study, we used the homology method and computed tomography images to quantify emphysema. METHODS: This study included 112 patients who had undergone computed tomography and pulmonary function test. Low-attenuation lung regions were evaluated by the homology method, and homology-based emphysema quantification (b0, b1, nb0, nb1, and R) was performed. For comparison, the percentage of low-attenuation lung area (LAA%) was also obtained. Relationships between emphysema quantification and pulmonary function test results were evaluated by Pearson's correlation coefficients. In addition to the correlation, the patients were divided into the following three groups based on guidelines of the Global initiative for chronic Obstructive Lung Disease: Group A, nonsmokers; Group B, smokers without COPD, mild COPD, and moderate COPD; Group C, severe COPD and very severe COPD. The homology-based emphysema quantification and LAA% were compared among these groups. RESULTS: For forced expiratory volume in 1 second/forced vital capacity, the correlation coefficients were as follows: LAA%, -0.603; b0, -0.460; b1, -0.500; nb0, -0.449; nb1, -0.524; and R, -0.574. For forced expiratory volume in 1 second, the coefficients were as follows: LAA%, 0.461; b0, -0.173; b1, -0.314; nb0, -0.191; nb1, -0.329; and R, -0.409. Between Groups A and B, difference in nb0 was significant (P-value = 0.00858), and those in the other types of quantification were not significant. CONCLUSION: Feasibility of the homology-based emphysema quantification was validated. The homology-based emphysema quantification was useful for the assessment of emphysema severity. PMID- 27660429 TI - Inflammatory biomarkers in asthma-COPD overlap syndrome. AB - BACKGROUND: The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS) remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort. METHODS: We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40-90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were evaluated. RESULTS: A total of 257 patients with COPD were identified, including 37 (14.4%) with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001). Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively). Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for ACOS diagnosis. CONCLUSION: These results provide evidence that these inflammatory biomarkers can be used to support the diagnosis of ACOS. PMID- 27660432 TI - Fractional exhaled nitric oxide levels in asthma-COPD overlap syndrome: analysis of the National Health and Nutrition Examination Survey, 2007-2012. AB - PURPOSE: Recent studies propose TH2-mediated inflammation in patients with asthma chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). However, little is known about whether fractional exhaled nitric oxide (FeNO) differs between patients with ACOS and those with COPD alone. To address this knowledge gap, a nationally representative sample was analyzed to determine the difference in FeNO levels between patients with ACOS and those with COPD alone in the US population. PATIENTS AND METHODS: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2007 through 2012. All subjects aged >=40 years with COPD were identified. ACOS was defined as self reported wheezing in past 12 months plus bronchodilator response (forced expiratory volume increase of >200 mL and >12%) or self-reported physician diagnosis of asthma. RESULTS: A total of 197 subjects with COPD were identified in the National Health and Nutrition Examination Survey. Of these, 23% met the criteria of ACOS. The FeNO level was higher in subjects with ACOS compared with those with COPD alone in both unadjusted (mean 21.2 ppb vs 13.0 ppb; difference, 8.2 [95% CI, 0.2 to 16.2]; P=0.045) and adjusted (difference, 8.2 [95% CI, 0.9 to 15.5]; P=0.03) analyses. Although there was no significant difference among current smokers, the FeNO level was significantly higher in non-current smokers with ACOS than nonsmokers with COPD alone (mean 31.9 ppb vs 20.3 ppb; adjusted difference, 20.5 [95% CI, 4.4 to 36.6]; P=0.02). In a sensitivity analysis using an alternative definition of ACOS, the results did not change materially. The diagnostic value of FeNO to discriminate ACOS from COPD alone was not sufficient, with the area under the curve of 0.63 (95% CI, 0.54 to 0.72). CONCLUSION: By using nationally representative US data, it was found that 23% of COPD subjects met the ACOS criteria and also that the FeNO level was higher in subjects with ACOS compared with those with COPD alone, particularly in non-current smokers. PMID- 27660431 TI - Neutral sphingomyelinase-2, acid sphingomyelinase, and ceramide levels in COPD patients compared to controls. AB - BACKGROUND: Increased pulmonary ceramide levels are suggested to play a causative role in lung diseases including COPD. Neutral sphingomyelinase-2 (nSMase-2) and acid SMase (aSMase), which hydrolyze sphingomyelin to produce ceramide, are activated by a range of cellular stresses, including inflammatory cytokines and pathogens, but notably cigarette smoke appears to only activate nSMase-2. Our primary objective was to investigate nSMase-2 and aSMase protein localization and quantification in lung tissue from nonsmokers (NS), smokers (S), and COPD patients. In addition, various ceramide species (C16, C18, and C20) were measured in alveolar macrophages from COPD patients versus controls. MATERIALS AND METHODS: Patients undergoing surgical resection for suspected or confirmed lung cancer were recruited, and nSMase-2 and aSMase protein was investigated in different areas of lung tissue (small airways, alveolar walls, subepithelium, and alveolar macrophages) by immunohistochemistry. Ceramide species were measured in alveolar macrophages from COPD patients and controls by mass spectrometry. RESULTS: nSMase-2 and aSMase were detected in the majority of small airways. There was a significant increase in nSMase-2 immunoreactivity in alveolar macrophages from COPD patients (54%) compared with NS (31.7%) (P<0.05), and in aSMase immunoreactivity in COPD (68.2%) and S (69.5%) alveolar macrophages compared with NS (52.4%) (P<0.05). aSMase labeling was also increased in the subepithelium and alveolar walls of S compared with NS. Ceramide (C20) was significantly increased in alveolar macrophages from COPD patients compared with controls. CONCLUSION: nSMase-2 and aSMase are both increased in COPD alveolar macrophages at the protein level; this may contribute toward the elevated ceramide (C20) detected in alveolar macrophages from COPD patients. PMID- 27660433 TI - Static lung volume should be used to confirm restrictive lung disease. PMID- 27660434 TI - Carbon nanotube-based substrates promote cardiogenesis in brown adipose-derived stem cells via beta1-integrin-dependent TGF-beta1 signaling pathway. AB - Stem cell-based therapy remains one of the promising approaches for cardiac repair and regeneration. However, its applications are restricted by the limited efficacy of cardiac differentiation. To address this issue, we examined whether carbon nanotubes (CNTs) would provide an instructive extracellular microenvironment to facilitate cardiogenesis in brown adipose-derived stem cells (BASCs) and to elucidate the underlying signaling pathways. In this study, we systematically investigated a series of cellular responses of BASCs due to the incorporation of CNTs into collagen (CNT-Col) substrates that promoted cell adhesion, spreading, and growth. Moreover, we found that CNT-Col substrates remarkably improved the efficiency of BASCs cardiogenesis by using fluorescence staining and quantitative real-time reverse transcription-polymerase chain reaction. Critically, CNTs in the substrates accelerated the maturation of BASCs derived cardiomyocytes. Furthermore, the underlying mechanism for promotion of BASCs cardiac differentiation by CNTs was determined by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction, and Western blotting assay. It is notable that beta1-integrin-dependent TGF-beta1 signaling pathway modulates the facilitative effect of CNTs in cardiac differentiation of BASCs. Therefore, it is an efficient approach to regulate cardiac differentiation of BASCs by the incorporation of CNTs into the native matrix. Importantly, our findings can not only facilitate the mechanistic understanding of molecular events initiating cardiac differentiation in stem cells, but also offer a potentially safer source for cardiac regenerative medicine. PMID- 27660436 TI - Inhibitory effect of magnetic Fe3O4 nanoparticles coloaded with homoharringtonine on human leukemia cells in vivo and in vitro. AB - Homoharringtonine (HHT), a natural cephalotaxine alkaloid, has been used in the People's Republic of China for treatment of leukemia for >3 decades. Here, we employed magnetic Fe3O4 nanoparticles (MNP-Fe3O4) to improve the therapeutic effect of HHT and investigated its biological effects. Within a certain range of concentrations, the HHT-MNP-Fe3O4 showed a more enhanced inhibitory effect on the selected myeloid leukemia cell lines than HHT alone. Compared with HHT, HHT-MNP Fe3O4 could induce more extensive apoptosis in leukemia cells, which also showed more pronounced cell arrests at G0/G1 phase. HHT-MNP-Fe3O4 enhanced antitumor activity by downregulating myeloid cell leukemia-1, which could inhibit the activation of caspase-3 and poly-ADP-ribose polymerase. In vivo experiments using tumor-bearing animal models showed that the mean tumor volume with HHT-MNP-Fe3O4 was significantly smaller than that with HHT alone (193+/-26 mm3 versus 457+/-100 mm3, P<0.05), while the mean weight was 0.67+/-0.03 g versus 1.42+/-0.56 g (P<0.05). Immunohistochemical study showed fewer myeloid cell leukemia-1-stained cells in mice treated with HHT-MNP-Fe3O4 than with the controls. These findings provide a more efficient delivery system for HHT in the treatment of hematological malignancy. PMID- 27660435 TI - Self-assembled nanoparticles based on amphiphilic chitosan derivative and arginine for oral curcumin delivery. AB - Curcumin (Cur) is a striking anticancer agent, but its low aqueous solubility, poor absorption, hasty metabolism, and elimination limit its oral bioavailability and consequently hinder its development as a drug. To redress these limitations, amphiphilic chitosan (CS) conjugate with improved mucoadhesion and solubility over a wider pH range was developed by modification with hydrophobic acrylonitrile (AN) and hydrophilic arginine (Arg); the synthesized conjugate (AN CS-Arg), which was well characterized by Fourier transform infrared and 1H nuclear magnetic resonance spectroscopy. Results of critical aggregation concentration revealed that the AN-CS-Arg conjugate had low critical aggregation concentration and was prone to form self-assembled nanoparticles (NPs) in aqueous medium. Cur-encapsulated AN-CS-Arg NPs (AN-CS-Arg/Cur NPs) were developed by a simple sonication method and characterized for the physicochemical parameters such as zeta potential, particle size, and drug encapsulation. The results showed that zeta potential of the prepared NPs was 40.1+/-2.81 mV and the average size was ~218 nm. A considerable improvement in the aqueous solubility of Cur was observed after encapsulation into AN-CS-Arg/Cur NPs. With the increase in Cur concentration, loading efficiency increased but encapsulation efficiency decreased. The in vitro release profile exhibited sustained release pattern from the AN-CS-Arg/Cur NPs in typical biological buffers. The ex vivo mucoadhesion study revealed that AN-CS-Arg/Cur NPs had greater mucoadhesion than the control CS NPs. Compared with free Cur solution, AN-CS-Arg/Cur NPs showed stronger dose dependent cytotoxicity against HT-29 cells. In addition, it was observed that cell uptake of AN-CS-Arg/Cur NPs was much higher compared with free Cur. Furthermore, the in vivo pharmacokinetic results in rats demonstrated that the AN CS-Arg/Cur NPs could remarkably improve the oral bioavailability of Cur. Therefore, the developed AN-CS-Arg/Cur NPs might be a promising nano-candidate for oral delivery of Cur. PMID- 27660437 TI - Construction of magnetic-carbon-quantum-dots-probe-labeled apoferritin nanocages for bioimaging and targeted therapy. AB - Carbon dots (CDs) are one of the most highlighted carbon-based materials for biological applications, such as optical imaging nanoprobes, which are used for labeling cells in cancer treatment mainly due to their biocompatibility and unique optical properties. In this study, gadolinium (Gd)-complex-containing CDs were obtained through a one-step microwave method to develop multimodal nanoprobes integrating the advantages of optical and magnetic imaging. The obtained Gd-CDs exhibited highly fluorescent properties with excellent water solubility and biological compatibility. Natural apoferritin (AFn) nanocages, an excellent drug delivery carrier, are hollow in structure, with their pH dependent, unfolding-refolding process at pH 2.0 and 7.4. The chemotherapeutic drug doxorubicin (DOX) can be highly effective and encapsulated into AFn cavity. A widely used tumor-targeting molecule, folic acid (FA), functionalized the surface of AFn to obtain an active tumor targeting effect on MCF-7 cells and malignant tumors in mice models. In this study, an AFn nanocarrier encapsulating high concentration of DOX labeled with magnetic and fluorescent Gd-CDs probe was developed. Gd-CDs exhibited a unique green photoluminescence and almost no toxicity compared with free GdCl3. Furthermore, Gd-doped CDs significantly increased the circulation time and decreased the toxicity of Gd3+ in in vitro and in vivo magnetic resonance imaging, which demonstrated that the AFn nanocages labeled with Gd-CD compounds could serve as an excellent T1 contrast agent for magnetic resonance imaging. The self-assembling multifunctional Gd-CDs/AFn (DOX)/FA nanoparticles have a great potential for cancer theranostic applications. PMID- 27660438 TI - Green synthesis of silver nanoparticles using Pimpinella anisum seeds: antimicrobial activity and cytotoxicity on human neonatal skin stromal cells and colon cancer cells. AB - BACKGROUND: The present study focused on a simple and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) with multipurpose anticancer and antimicrobial activities. MATERIALS AND METHODS: We studied a green synthesis route to produce AgNPs by using an aqueous extract of Pimpinella anisum seeds (3 mM). Their antimicrobial activity and cytotoxicity on human neonatal skin stromal cells (hSSCs) and colon cancer cells (HT115) were assessed. RESULTS: A biophysical characterization of the synthesized AgNPs was realized: the morphology of AgNPs was determined by transmission electron microscopy, energy dispersive spectroscopy, X-ray powder diffraction, and ultraviolet-vis absorption spectroscopy. Transmission electron microscopy showed spherical shapes of AgNPs of P. anisum seed extracts with a 3.2 nm minimum diameter and average diameter ranging from 3.2 to 16 nm. X-ray powder diffraction highlighted the crystalline nature of the nanoparticles, ultraviolet-vis absorption spectroscopy was used to monitor their synthesis, and Fourier transform infrared spectroscopy showed the main reducing groups from the seed extract. Energy dispersive spectroscopy was used to confirm the presence of elemental silver. We evaluated the antimicrobial potential of green-synthesized AgNPs against five infectious bacteria: Staphylococcus pyogenes (29213), Acinetobacter baumannii (4436), Klebsiella pneumoniae (G455), Salmonella typhi, and Pseudomonas aeruginosa. In addition, we focused on the toxicological effects of AgNPs against hSSC cells and HT115 cells by using in vitro proliferation tests and cell viability assays. Among the different tested concentrations of nanoparticles, doses < 10 ug showed few adverse effects on cell proliferation without variations in viability, whereas doses >10 ug led to increased cytotoxicity. CONCLUSION: Overall, our results highlighted the capacity of P. anisum-synthesized AgNPs as novel and cheap bioreducing agents for eco-friendly nanosynthetical routes. The data confirm the multipurpose potential of plant-borne reducing and stabilizing agents in nanotechnology. PMID- 27660439 TI - 3-Aminopropylsilane-modified iron oxide nanoparticles for contrast-enhanced magnetic resonance imaging of liver lesions induced by Opisthorchis felineus. AB - PURPOSE: Liver fluke causes severe liver damage in an infected human. However, the infection often remains neglected due to the lack of pathognomonic signs. Nanoparticle-enhanced magnetic resonance imaging (MRI) offers a promising technique for detecting liver lesions induced by parasites. MATERIALS AND METHODS: Surface modification of iron oxide nanoparticles produced by coprecipitation from a solution of Fe3+ and Fe2+ salts using 3-aminopropylsilane (APS) was carried out. The APS-modified nanoparticles were characterized by transmission electron microscopy, fourier transform infrared spectroscopy, and thermogravimetric analysis. Magnetic resonance properties of MNPs were investigated in vitro and in vivo. RESULTS: The amount of APS grafted on the surface of nanoparticles (0.60+/-0.06 mmol g-1) was calculated based on elemental analysis and infrared spectroscopy data. According to transmission electron microscopy data, there were no essential changes in the structure of nanoparticles during the modification. The APS-modified nanoparticles exhibit high magnetic properties; the calculated relaxivity r2 was 271 mmol-1 s-1. To obtain suspension with optimal hydrodynamic characteristics, amino groups on the surface of nanoparticles were converted into an ionic form with HCl. Cellular uptake of modified nanoparticles by rat hepatoma cells and human monocytes in vitro was 74.1+/-4.5 and 10.0+/-3.7 pg [Fe] per cell, respectively. Low cytotoxicity of the nanoparticles was confirmed by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide and Annexin V/7-aminoactinomycin D flow cytometry assays. For the first time, magnetic nanoparticles were applied for contrast enhanced MRI of liver lesions induced by Opisthorchis felineus. CONCLUSION: The synthesized APS-modified iron oxide nanoparticles showed high efficiency as an MRI contrast agent for the evaluation of opisthorchiasis-related liver damage. PMID- 27660440 TI - Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation. AB - Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl-sn-glycero-3 phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol(r) while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes. PMID- 27660441 TI - Pluronic(r) P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells. AB - Here, we developed Pluronic(r) P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB-VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori. PMID- 27660442 TI - Nanoemulsion as a carrier to improve the topical anti-inflammatory activity of stem bark extract of Rapanea ferruginea. AB - The aim of this study was to develop nanoemulsion containing soft extract of stem bark of Rapanea ferruginea to improve the topical delivery and anti-inflammatory activity. The extract of R. ferruginea stem bark was incorporated into the oily phase of the nanoemulsion by the method of phase inversion at low energy. The developed nanoemulsion had an average droplet size of 47.88+/-8.20 nm and a polydispersibility index of 0.228. Uniformity of size, spherical shape of droplet, and absence of clusters were confirmed by transmission electronic microscopy. The zeta potential was -34.7+/-1.15 mV. The nanoemulsion showed a moderate degree of skin irritation in the agarose overlay assay in vitro. The content of the extract markers, myrsinoic acids A and B, was 54.10+/-0.08 and 53.03 MUg/g in the formulation, respectively. The formulation demonstrated pseudoplastic and thixotropic rheological behavior. In vitro release of chemical markers was controlled by diffusion mechanism. An extract-loaded nanoemulsion showed a topical anti-inflammatory activity in a croton oil-induced edema ear model, with a decrease in tumor necrosis factor release and myeloperoxidase activity. The nanoemulsion was 160% more efficient than the conventional cream containing 0.13% of the extract. The nanoemulsion showed suitable properties as a carrier for topical use of R. ferruginea extract and the approach for improving the topical anti-inflammatory activity. PMID- 27660443 TI - Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation. AB - Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent. PMID- 27660444 TI - Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells. AB - In the present study, a poly-l-lactide/silk fibroin (PL-SF) bilayer scaffold seeded with allogenic bone marrow stromal cells (BMSCs) was investigated as a potential approach for bladder tissue engineering in a model of partial bladder wall cystectomy in rabbits. The inner porous layer of the scaffold produced from silk fibroin was designed to promote cell proliferation and the outer layer produced from poly-l-lactic acid to serve as a waterproof barrier. To compare the feasibility and efficacy of BMSC application in the reconstruction of bladder defects, 12 adult male rabbits were divided into experimental and control groups (six animals each) that received a scaffold seeded with BMSCs or an acellular one, respectively. For BMSC tracking in the graft in in vivo studies using magnetic resonance imaging, cells were labeled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated high intracellular incorporation of nanoparticles and the absence of a toxic influence on BMSC viability and proliferation. Following implantation of the graft with BMSCs into the bladder, we observed integration of the scaffold with surrounding bladder tissues (as detected by magnetic resonance imaging). During the follow-up period of 12 weeks, labeled BMSCs resided in the implanted scaffold. The functional activity of the reconstructed bladder was confirmed by electromyography. Subsequent histological assay demonstrated enhanced biointegrative properties of the PL-SF scaffold with cells in comparison to the control graft, as related to complete regeneration of the smooth muscle and urothelium tissues in the implant. Confocal microscopy studies confirmed the presence of the superparamagnetic iron oxide nanoparticle labeled BMSCs in newly formed bladder layers, thus indicating the role of stem cells in bladder regeneration. The results of this study demonstrate that application of a PL-SF scaffold seeded with allogenic BMSCs can enhance biointegration of the graft in vivo and support bladder tissue regeneration and function. PMID- 27660445 TI - Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies. AB - Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. PMID- 27660446 TI - Codelivery of thioridazine and doxorubicin using nanoparticles for effective breast cancer therapy. AB - Cancer chemotherapy can benefit from the combination of different anticancer drugs. Here, we prepared doxorubicin (Dox)- and thioridazine (Thio)-coloaded methoxy poly(ethylene glycol)-poly(l-lactic acid) (MPEG-PLA) nanoparticles (NPs) for breast cancer therapy. These NPs have an average particle size of 27 nm. The drug loading efficiencies of Thio and Dox are 4.71% and 1.98%, respectively. Compared to the treatment of Thio or Dox alone, the combination of Thio and Dox exhibited a synergistic effect in inhibiting the growth of 4T1 breast cancer cells in vitro. In addition, the Thio- and Dox-coloaded MPEG-PLA NPs could efficiently suppress the growth of breast cancer cells in vivo. This study suggests that Thio- and Dox-coloaded MPEG-PLA NPs might have potential applications in breast cancer treatment. PMID- 27660447 TI - Design, characterization, and biological evaluation of curcumin-loaded surfactant based systems for topical drug delivery. AB - From previous studies, it has been found that curcumin exhibits an anti inflammatory activity and is being used for the treatment of skin disorders; however, it is hydrophobic and has weak penetrating ability, resulting in poor drug transport through the stratum corneum. The aim of this study was to develop liquid crystalline systems for topical administration of curcumin for the treatment of inflammation. These liquid crystalline systems were developed from oleic acid, polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol, and water as the surfactant, oil phase, and aqueous phase, respectively. These systems were characterized, and polarized light microscopy showed anisotropy with lamellar mesophases (Formulation 1) and hexagonal mesophases (Formulations 2 and 3), which were confirmed by the peak ratio measured using small-angle X-ray scattering. In addition, rheological tests revealed that the formulations exhibited gel-like behavior (G'>G"), as evidenced by the increased G' values that indicate structured systems. Texture profile analysis showed that hexagonal mesophases have high values of hardness, adhesiveness, and compressibility, which indicate structured systems. In vitro studies on bioadhesion revealed that the hexagonal mesophases increased the bioadhesiveness of the systems to the skin of the pig ear. An in vivo inflammation experiment showed that the curcumin-loaded hexagonal mesophase exhibited an anti-inflammatory activity as compared to the positive control (dexamethasone). The results suggest that this system has a potential to be used as a bioadhesive vehicle for the topical administration of curcumin. Therefore, it is possible to conclude that these systems can be used for the optimization of drug delivery systems to the skin. PMID- 27660448 TI - d-alpha-Tocopheryl polyethylene glycol succinate/Solutol HS 15 mixed micelles for the delivery of baohuoside I against non-small-cell lung cancer: optimization and in vitro, in vivo evaluation. AB - Baohuoside I, extracted from the Herba epimedii, is an effective but a poorly soluble antitumor drug. To improve its solubility, formulation of baohuoside I loaded mixed micelles with d-alpha-tocopheryl polyethylene glycol succinate and Solutol HS 15 (BTSM) has been developed in this study. We performed a systematic comparative evaluation of the antiproliferative effect, cellular uptake, antitumor efficacy, and in vivo tumor targeting of these micelles using non-small cell lung cancer (NSCLC) A549 cells. Results showed that the obtained micelles have a mean particle size of ~62.54 nm, and the size of micelles was narrowly distributed. With the improved cellular uptake, BTSM displayed a more potent anti proliferative action on A549 cell lines than baohuoside I; half-maximal inhibitory concentration was 7.83 vs 20.37 ug/mL, respectively. The antitumor efficacy test in nude mice showed that BTSM exhibited significantly higher antitumor activity against NSCLC with lesser toxic effects on normal tissues. The imaging study for in vivo targeting demonstrated that the mixed micelles formulation achieved effective and targeted drug delivery. Therefore, BTSM might be a potential antitumor formulation. PMID- 27660449 TI - The interactive effects of ketamine and magnesium upon depressive-like pathology. AB - Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration. However, it is also a drug with an abusive potential and can have marked side effects. Hence, this study aimed at enhancing the antidepressant-like effects of ketamine (allowing for lower dosing regimens) by coadministering magnesium hydroaspartate (Mg(2+) normally affects the same receptors as ketamine) and also assessed whether an Mg(2+)-deficient diet would modify the impact of ketamine. It was found that a single 15 mg/kg dose of ketamine did indeed induce rapid antidepressant-like effects in the forced swim test but did not affect brain levels of the brain-derived neurotrophic factor. Contrary to our hypothesis, magnesium administration or deficiency did not influence the impact of ketamine on these outcomes. Thus, these data do not support the use of magnesium as an adjunct agent and instead suggest that further research involving other antidepressant and animal models is required to confirm the present findings. PMID- 27660450 TI - Late life bipolar disorder evolving into frontotemporal dementia mimic. AB - OBJECTIVES: Although bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series. CASES: From our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3-7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases. CONCLUSION: Symptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical progression. Functional involvement of the frontal-subcortical networks might play a role. PMID- 27660452 TI - Prescription patterns of benzodiazepines in the Lebanese adult population: a cross-sectional study. AB - This study assessed the profile of benzodiazepine (BDZ) users in Lebanon. Adult patients visiting the pharmacies with prescriptions of BDZs were included in the study. Seven hundred and eighty-six current BDZ users were included, of whom 54.2% were females. Twenty-three percent reported being alcohol consumers and were mostly males. The two most commonly used BDZs were alprazolam (34.6%) and bromazepam (33.6%). The indication for use was mainly anxiety (44.4%), insomnia (22.5%), and depression (15.9%). The prescribing physicians were primarily psychiatrists (43.2%), followed by general practitioners (29.7%). Forty percent had been taking the drug for more than a year. Among those using BDZs for at least 1 month, 35.5% increased the dose with time. Thirty-three percent reported having experienced side effects. Eighteen patients (2.3%) reported taking more than one BDZ concomitantly, while 18.3% were taking drugs that should not be prescribed along with BDZs. In conclusion, the use of BDZs is highest among females, especially for the treatment of anxiety. Moreover, continuous use of the drugs for more than a year as well as significant potential drug interactions was identified. PMID- 27660451 TI - Insomnia in patients on hemodialysis for a short versus long duration. AB - BACKGROUND: Many studies have investigated insomnia and the factors associated with this condition in hemodialysis (HD) patients, although the influence of HD duration has not been thoroughly investigated. In the present study, we investigated the factors, especially the duration of HD, associated with insomnia in HD patients. PATIENTS AND METHODS: A total of 138 patients undergoing HD were recruited, and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI) was used to assess the quality of sleep. Subjects with a total PSQI score up to 4 and those with a score of at least 5 were identified as normal subjects and subjects with insomnia, respectively. Additionally, we assessed restless legs syndrome, depression using the Center for Epidemiologic Studies Depression Scale, and health-related quality of life (QOL) using the Short Form 8 Health Survey. We divided the subjects into two groups according to the median HD duration. RESULTS: The prevalence rate of insomnia was 54.3% among all the subjects. Twenty one subjects (15.2%) had depression, 26 (18.8%) had restless legs syndrome, and 75 (54.3%) had insomnia. The median HD duration was 4 years. The scores of components 1 and 4 of the PSQI, subjective sleep quality and habitual sleep efficiency, did not show a significant difference between the normal and insomnia groups. The score of component 7, daytime dysfunction, showed a significant difference between the short and long HD duration groups. In multiple regression analysis, the score of the Short Form 8 Health Survey showed a significant association with the PSQI score in the long HD duration group, but no variable showed a significant association in the short HD duration group. CONCLUSION: Patients with a longer duration of HD indicated that insomnia has an influence on their daily activities, with a significant association between insomnia and QOL. Greater attention should be paid to poor QOL and troubles in daily activities caused by insomnia in patients with a longer HD duration. PMID- 27660453 TI - Clinical analysis of contributors to the delayed gallbladder opacification following the use of water-soluble contrast medium. AB - OBJECTIVES: Gallbladder opacification (GBO) on computed tomography (CT) imaging may obscure certain pathological or emergent conditions in the gallbladder, such as neoplasms, stones, and hemorrhagic cholecystitis. This study aimed to investigate the clinical contributing factors that could predict the presence of delayed GBO determined by CT. METHODS: This study retrospectively evaluated 243 consecutive patients who received enhanced CT or intravenous pyelography imaging and then underwent abdominal CT imaging within 5 days. According to the interval between imaging, the patients were divided into group A (1 day), group B (2 or 3 days), and group C (4 or 5 days). Three radiologists evaluated CT images to determine GBO. Fisher's exact test and multivariate backward stepwise elimination logistic regression were performed. RESULTS: Positive GBO was significantly associated with the interval between imaging studies, contrast type, contrast volume, renal function, and hypertransaminasemia (P<0.05). Multivariate backward stepwise elimination logistic regression analysis of the three groups identified contrast type and hypertransaminasemia as independent predictors of GBO in group B patients (odds ratio [OR], 13.52, 95% confidence interval [CI], 1.72-106.38 and OR, 3.43, 95% CI, 1.31-8.98, respectively; P<0.05). Hypertransaminasemia was the only independent predictor of GBO in group C patients with an OR of 7.2 (95% CI, 1.62-31.73). Hypertransaminasemia was noted in three patients (100%) who initially underwent imaging 5 days prior to GBO. CONCLUSION: Delayed GBO on CT imaging may be associated with laboratory hypertransaminasemia, particularly in patients receiving contrast medium over a period of >=4 days. A detailed clinical history, physical examination, and further workup are of paramount importance for investigating the underlying cause behind the hypertransaminasemia. PMID- 27660454 TI - Retargeting the management of hypercholesterolemia - focus on evolocumab. AB - Hypercholesterolemia is one of the main risk factors for atherosclerosis and cardiovascular diseases. The treatment is based on the modification of the diet and lifestyle and if necessary on a pharmacological therapy. The most widely used drugs are the inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (statins); nevertheless, many patients do not reach optimal levels of low-density lipoprotein-cholesterol (LDL-C) even with maximal dosage of statins (eventually associated to ezetimibe) or present side effects, which do not allow them to continue the treatment. Inhibitors of PCSK9 represent a new therapeutic approach for lowering LDL-C. Evolocumab and alirocumab are human monoclonal antibodies, which bind to extracellular PCSK9 and thus interfere with the degradation of low density lipoprotein receptor. Evolocumab use is approved for the treatment of patients with heterozygous familial hypercholesterolemia (FH) and homozygous FH as an adjunct to diet and maximally tolerated statin therapy or for subjects with clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Phase III clinical trials have demonstrated the effectiveness of evolocumab (140 mg/every 2 weeks or 420 mg/month, via subcutaneous injection) in monotherapy and in combination with statins, in the treatment of patients intolerant to statins or with FH. In monotherapy, it reduces LDL-C by 55%, and its association with statins leads to a reduction of LDL-C by up to 63%-75%. Evolocumab has been demonstrated to be safe and well tolerated. Ongoing clinical trials are assessing the long-term effects of evolocumab on the incidence of cardiovascular risk, safety, and tolerability. This review resumes the available clinical evidence on the efficacy and safety of evolocumab, for which a relatively large amount of clinical data are currently available, and discusses the retargeting of cholesterol-lowering therapy in clinical practice. PMID- 27660455 TI - Changes in oxidative stress from tracheal aspirates sampled during chest physical therapy in hospitalized intubated infant patients with pneumonia and secretion retention. AB - OBJECTIVE: This study aimed to show the changes in oxidative stress and clinical condition from either chest physical therapy (CPT) or CPT with aerosol treatment in infant patients with pneumonia. METHODS: From 52 intubated patients, three groups were composed: groups A, B, and C comprising 21 patients aged 5.3+/-0.6 months (CPT program), 20 patients aged 5.6+/-0.7 months (aerosol treatment before CPT program), and eleven patients aged 5.0+/-0.35 months (control), respectively. CPT was composed of manual percussion and vibration before suction in a specific position for draining secretion and re-expanding collapsed lungs. Groups A and B received three sessions of treatment three times daily for 6 days, when tracheal aspirates were collected for evaluating oxidative stress markers for the thiol group: vitamin E, thiobarbituric acid reactive substances-malondialdehyde, and hyarulonan. Furthermore, lung injury score and oxygenation index (PvO2/FiO2 ratio) were recorded daily. RESULTS: All parameters in group C did not change statistically during study. The thiol group increased significantly in group A after day 4, and increased significantly on days 3 and 6 when compared to day 1 in group B. Vitamin E levels increased significantly on days 3, 5, and 6 in group A, and days 3, 4, and 6 in group B, when compared to day 1. Whereas, the thiobarbituric acid reactive substances-malondialdehyde adduct showed a significant reduction after day 4 in groups A and B, when compared to day 1. Hyarulonan levels showed a significant reduction after day 3 in group A and on day 2 in group B. In addition, lung injury score decreased slightly and nonsignificantly in groups A and B, whereas the oxygenation index increased significantly after day 4 in group A and on day 6 in group B. CONCLUSION: These preliminary results suggest that CPT with or without aerosol treatment possibly reduces oxidative stress and enhances oxygenation status in infant patients. PMID- 27660456 TI - Patients' safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use? AB - INTRODUCTION: Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN) PROtectTM coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients' risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect. METHODS: Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1-4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects. RESULTS: Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean inflammation and renal retention markers, but no gentamicin associated side effects could be linked to implantation. Furthermore, no allergic reactions could be detected during our study. CONCLUSION: Our findings suggest that there is no relevant release of gentamicin into the systemic circulation causing a systemic effect, and serious side effects due to gentamicin-coated tibia nails should not be feared. Postoperative monitoring of renal function does not seem necessary because of the implantation of ETN PROtect. PMID- 27660457 TI - The association of serum gamma-glutamyl transpeptidase level and other laboratory parameters with blood pressure in hypertensive patients under ambulatory blood pressure monitoring. AB - BACKGROUND: Hypertension is a very important cause of morbidity and mortality. Serum gamma-glutamyl transpeptidase (GGT) is a biomarker of oxidative stress and associated with increased risk of hypertension and diabetes. The aim of this study was to evaluate the association of serum GGT level, which is an early marker of inflammation and endothelial dysfunction, with the deterioration of the diurnal rhythm of the blood pressure. METHODS: A total of 171 patients with hypertension were included in this study. Patients whose nighttime mean blood pressure, measured via ambulatory blood pressure monitoring, decreased between 10% and 20% compared with the daytime mean blood pressure were defined as "dippers", whereas patients with a nighttime blood pressure decrease lower than 10% were defined as "non-dippers". RESULTS: A total of 99 hypertensive patients (65 females/34 males) were classified as dippers and 72 patients (48 females/24 males) as non-dippers. The mean age of the non-dipper group was significantly greater than the dipper group. Serum GGT, C-reactive protein and uric acid levels were significantly higher among patients in the non-dipper group. Negative correlations were detected between GGT levels and diurnal systolic and diastolic blood pressure decreases. CONCLUSION: Our findings revealed that GGT level was higher in the non-dipper group, and was negatively correlated with the nighttime decrease of diurnal blood pressure. C-reactive protein and uric acid levels were also higher in the non-dipper group. However, future randomized controlled prospective studies with larger patient populations are necessary to confirm our findings. PMID- 27660459 TI - "That's Where the Arguments Come in": A Qualitative Analysis of Booster Sessions Following a Brief Intervention for Drug Use and Intimate Partner Violence in the Emergency Department. AB - Although booster phone calls have been used to enhance the impact of brief interventions in the emergency department, there has been less number of studies describing the content of these boosters. We conducted a qualitative analysis of booster calls occurring two weeks after an initial Web-based intervention for drug use and intimate partner violence (IPV) among women presenting for emergency care, with the objective of identifying the following: progress toward goals set during the initial emergency department visit, barriers to positive change, and additional resources and services needed in order to inform improvements in future booster sessions. The initial thematic framework was developed by summarizing codes by major themes and subthemes; the study team collaboratively decided on a final thematic framework. Eighteen participants completed the booster call. Most of them described a therapeutic purpose for their drug use. Altering the social milieu was the primary means of drug use change; this seemed to increase isolation of women already in abusive relationships. Women described IPV as interwoven with drug use. Participants identified challenges in attending substance use treatment service and domestic violence agencies. Women with substance use disorders and in abusive relationships face specific barriers to reducing drug use and to seeking help after a brief intervention. PMID- 27660458 TI - Overview of guidelines for the management of dyslipidemia: EU perspectives. AB - Modern medicine is characterized by a continuous genesis of evidence making it very difficult to translate the latest findings into a better clinical practice. Clinical practice guidelines (CPG) emerge to provide clinicians evidence-based recommendations for their daily clinical practice. However, the high number of existing CPG as well as the usual differences in the given recommendations usually increases the clinician's confusion and doubts. It has apparently been the case for the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol. These CPG proposed new and controversial concepts that have usually been considered an antagonist shift respective to European CPG. The most controversial published proposals are: 1) to consider evidence just from randomized clinical trials, 2) creation of a new cardiovascular (CV) risk calculator, 3) to consider reducing CV risk instead of reducing low-density lipoprotein cholesterol (LDLc) as the target of the treatment, and 4) consideration of statins as the only drugs for treatment. A deep analysis of the 2013 American College of Cardiology/American Heart Association CPG and comparison with the European ones show that from a practical and clinical point of view, there are more similarities than differences. To further help clinicians in their daily work, in the present globalized world, it is time to discuss and adopt a mutually agreed upon document created by both sides of the Atlantic. Probably it is not a short-term solution. Meanwhile, taking advantage of the similarities, the recommended practical attitude for the daily clinical practice should be based on 1) early detection of people with increased CV risk promoting the use of validated local scales, 2) reinforce the mainstream importance of nonpharmacological treatment, and 3) need for periodically monitoring response with analytical parameters (LDL or non-high density lipoprotein cholesterol) and global CV risk estimation. Technological solutions such as the big data technology could help to obtain high-quality evidence in an intermediate term. PMID- 27660460 TI - The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine Disrupting Chemicals. AB - An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children. PMID- 27660461 TI - Long-term results of definitive concurrent chemoradiotherapy using S-1 in the treatment of geriatric patients with esophageal cancer. AB - OBJECTIVE: The aim of this study was to investigate the efficiency and safety of using S-1 as monotherapy and maintenance therapy combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer. PATIENTS AND METHODS: From January 2009 to December 2010, 68 elderly patients were included. Radiotherapy was delivered with a daily fraction of 1.8-2.0 Gy to a total radiation dose of 54.0-60.0 Gy. Preplanned concurrent S-1 (80 mg/m(2)/d) was given on days 1-14, every 3 weeks. After concurrent chemoradiotherapy, maintenance S-1 was repeated up to four cycles. RESULTS: The median age of the enrolled patients was 76 years (range: 70-88 years), and the clinical stages were stage I (two patients), stage II (24 patients), stage III (28 patients), and stage IV (14 patients). A total of 51 (75.0%) patients finished treatment on schedule, with a median of five cycles of S-1, in which 35 (51.5%) patients achieved complete response. The median follow-up time was 42.7 months, and the median overall survival (OS) and progression-free survival (PFS) times were 25.7 months and 21.5 months, respectively. The 1-year, 3-year, and 5-year OS and PFS rates were 70.6%, 41.8%, and 25.9% and 68.1%, 32.9%, and 15.9%, respectively. Grade >=3 neutropenia and leukopenia were found in 14 patients and 13 patients, respectively. The most common nonhematologic toxicity was esophagitis including six patients and one patient with grades 3 and 4, respectively. Multivariate analysis revealed that cycles of S-1 and complete response were strong factors for OS and PFS. CONCLUSION: For geriatric patients with esophageal cancer, S-1 as monotherapy and maintenance chemotherapy in combination with definitive concurrent radiation therapy yielded satisfactory survival outcomes with tolerable toxicities. More studies are highly warranted to further clarify this issue. PMID- 27660462 TI - Association between insulin-like growth factor-binding protein-3 polymorphism-202 A/C and the risk of prostate cancer: a meta-analysis. AB - BACKGROUND: Some previous studies have investigated the relationship between insulin-like growth factor-binding protein-3 polymorphism and prostate cancer (PCa) susceptibility; however, the findings from those studies remain inconsistent. Hence, the aim of this meta-analysis was to provide a more reliable conclusion about such associations. METHODS: A meta-analysis based on twelve studies was conducted, and 8,341 PCa cases and 7,734 controls were included in this analysis. All relevant studies published till February 1, 2016, were identified by searching the databases such as PubMed, EMBASE, and Web of Science. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) in order to assess the strength of such associations. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. RESULTS: Several articles provided data only for particular genotypes; therefore, only dominant model analyses were carried out for all of these studies. Initially, the results from this analysis indicated that rs2854744 was not associated with PCa susceptibility (OR=1.12, 95% CI=0.996-1.2). However, after excluding one study due to its heterogeneity and publication bias, a significant relationship was detected between rs2854744 and PCa risk (OR=1.10, 95% CI=1.03-1.17). When stratified by genotyping method, significant results were detected only in the Sequenom method group (OR=1.13, 95% CI=1.04-1.22). Moreover, the results from a subgroup analysis that was conducted by using source of controls were significant only in the population-based control group. CONCLUSION: This meta-analysis suggested that the insulin-like growth factor-binding protein-3 polymorphism-202 A/C was associated with PCa susceptibility. PMID- 27660464 TI - A comparison study of pancreatic acinar cell carcinoma with ductal adenocarcinoma using computed tomography in Chinese patients. AB - Pancreatic acinar cell carcinoma (ACC) is a rare tumor that is difficult to diagnose preoperatively. The aim of this study was to evaluate and describe the computed tomography (CT) features of ACC and compare the results with pancreatic ductal adenocarcinoma (DAC) for improving preoperative diagnosis. The control group consisted of 34 patients with DAC collected from the pathology electronic database. The CT imaging from nine patients with pathologically confirmed ACC was retrospectively reviewed. Two radiologists independently assessed the tumor location, size, texture, and enhancement patterns. We found that 64.3% (9/14) of ACC tumors were homogeneous and 35.7% (5/14) had necrosis. The percentage of common bile duct and pancreatic ductal dilation was 14.3% (2/14) and 7.1% (1/14), respectively. The mean size of ACC was 50.1+/-24.2 mm. The mean attenuation of ACC was 35.4+/-3.9 Hounsfield unit (HU) before enhancement, 73.1+/-42.9 HU in arterial phase, and 71.8+/-15.6 HU in port venous phase. It is difficult to distinguish ACC from DAC preoperatively only based on CT findings. However, compared with DAC, we found that ACC tumors are likely to be larger and contain more heterogeneous intratumoral necrotic hypovascular regions, and less pancreatic ductal and common biliary dilation. PMID- 27660465 TI - Clinical implications of the coexpression of SRC1 and NANOG in HER-2 overexpressing breast cancers. AB - OBJECTIVE: Given the lack of clarity on the expression status of SRC1 protein in breast cancer, we attempted to ascertain the clinical implications of the expression of this protein in breast cancer. METHODS: Samples from 312 breast cancer patients who were followed up for 5 years were analyzed in this study. The associations of SRC1 expression and clinicopathological factors with the prognosis of breast cancer were determined. RESULTS: The 312 breast cancer patients underwent radical resection, and 155 (49.68%) of them demonstrated high expression of SRC1 protein. No significant differences were found for tumor size, estrogen receptor expression, or progesterone receptor expression (P=0.191, 0.888, or 0.163, respectively). It is noteworthy that SRC1 expression was found to be related to HER-2 and Ki-67 expression (P=0.044 and P=0.001, respectively). According to logistic regression analysis, SRC1 expression was also significantly correlated with Ki-67 and HER-2 expression (P=0.032 and P=0.001, respectively). Survival analysis showed that patients with a high expression of SRC1 and NANOG and those with SRC1 and NANOG coexpression had significantly poorer postoperative disease-specific survival than those with no expression in the HER-2-positive group (P=0.032, 0.01, and P=0.01, respectively). CONCLUSION: High SRC1 protein expression was related to the prognosis of HER-2-overexpressing breast cancers. PMID- 27660463 TI - Next-generation EGFR/HER tyrosine kinase inhibitors for the treatment of patients with non-small-cell lung cancer harboring EGFR mutations: a review of the evidence. AB - Tyrosine kinase inhibitors (TKIs) against human epidermal growth factor receptor (EGFR/HER) family have been introduced into the clinic to treat cancers, particularly non-small-cell lung cancer (NSCLC). There have been three generations of the EGFR/HER-TKIs. First-generation EGFR/HER-TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR TK domain, show a significant breakthrough treatment in selected NSCLC patients with activating EGFR mutations (actEGFRm) EGFR (L858R) and EGFR (Del19), in terms of safety, efficacy, and quality of life. However, all those responders inevitably develop acquired resistance within 12 months, because of the EGFR (T790M) mutation, which prevents TKI binding to ATP-pocket of EGFR by steric hindrance. The second generation EGFR/HER-TKIs were developed to prolong and maintain more potent response as well as overcome the resistance to the first-generation EGFR/HER TKIs. They are different from the first-generation EGFR/HER-TKIs by covalently binding to the ATP-binding site, irreversibly blocking enzymatic activation, and targeting EGFR/HER family members, including EGFR, HER2, and HER4. Preclinically, these compounds inhibit the enzymatic activation for actEGFRm, EGFR (T790M), and wtEGFR. The second-generation EGFR/HER-TKIs improve overall survival in cancer patients with actEGFRm in a modest way. However, they are not clinically active in overcoming EGFR (T790M) resistance, mainly because of dose-limiting toxicity due to simultaneous inhibition against wtEGFR. The third-generation EGFR/HER-TKIs selectively and irreversibly target EGFR (T790M) and actEGFRm while sparing wtEGFR. They yield promising efficacy in NSCLC patients with actEGFRm as well as EGFR (T790M) resistant to the first- and second-generation EGFR-TKIs. They also appear to have a lower incidence of toxicity due to the reduced inhibitory effect on wtEGFR. Currently, the first-generation EGFR/HER-TKIs gefitinib and erlotinib and second-generation EGFR/HER-TKI afatinib have been approved for use as the first-line treatment of metastatic NSCLC with actEGFRm. This review will summarize and evaluate a broad range of evidence of recent development of EGFR/HER-TKIs, with a focus on the second- and third-generation EGFR/HER-TKIs, in the treatment of patients with NSCLC harboring EGFR mutations. PMID- 27660466 TI - Osimertinib making a breakthrough in lung cancer targeted therapy. AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the evidence-based first-line treatment for advanced non-small-cell lung cancer that harbors sensitizing EGFR mutations (EGFRm(+)) such as exon 19 deletions and L858R substitutions in exon 21. However, acquired resistance to EGFR TKIs is mostly driven by a second-site EGFR T790M mutation, which negates their inhibitory activity. Osimertinib (AZD9291, TagrissoTM), an oral, third-generation EGFR TKI, has been designed to target the EGFR T790M mutation, while sparing wild-type EGFR. In this up-to-date review, focus is not only on the structure, mechanisms, and pharmacokinetics of osimertinib but also on summarizing clinical trials and making recommendations of osimertinib for patients with non-small-cell lung cancer. PMID- 27660468 TI - Lenalidomide, celecoxib, and azacitidine therapy for blastic plasmocytoid dendritic cell neoplasm: a case report. AB - Blastic plasmocytoid dendritic cell neoplasm is characterized by aggressive behavior with a tendency for systemic dissemination and a predilection for skin, lymph nodes, soft tissues, peripheral blood, or bone marrow. It usually occurs in elderly patients with a mean age between 60 and 70 years. Despite initial response to chemotherapy, the disease regularly relapses with a short median overall survival. Better outcomes have been reported with high-dose acute leukemia-like induction chemotherapy followed by consolidation with allogeneic hematopoietic stem cell transplantation. However, elderly patients are not candidates for intensive therapy or allogeneic stem cell transplantation. So, new active and tolerable drugs are needed. Our case illustrates that one cycle of lenalidomide and celecoxib provides at least a partial cutaneous and hematologic response, but this regimen was discontinued due to toxicity and followed by a consolidation/maintenance phase with azacitidine, thus achieving a final complete response with a much higher than expected progression-free and overall survival in an elderly patient with comorbidities. This information may be useful in the design of treatment approaches for elderly patients with blastic plasmocytoid dendritic cell neoplasm. However, it should be confirmed in clinical trials as well as by optimizing the induction and extending the consolidation/maintenance period to avoid early relapses after discontinuation and improve progression-free survival. PMID- 27660467 TI - Sunitinib: the antiangiogenic effects and beyond. AB - As a multitargeted kinase inhibitor, sunitinib has carved its way into demonstrating itself as a most effective tyrosine kinase inhibitor in the treatment of metastatic renal cell carcinoma. Mechanistically, sunitinib inhibits multiple receptor tyrosine kinases, especially those involved in angiogenesis, that is, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and proto-oncogene cKIT. Sunitinib has also been implicated in enhancing cancer invasiveness and metastasis. Mechanisms of resistance are poorly understood, but both intrinsic and acquired mechanisms are thought to be involved. While the side effects are manageable, sunitinib, like many other tyrosine kinase inhibitors, can be associated with serious toxicities that require careful management including frequent dose reductions. Although still in the early stage, emerging evidence points to an immunomodulatory role for sunitinib. It is also likely to contribute to the overall outcomes, especially those seen in metastatic renal cell carcinoma, and such effects are thought to be mediated by the proto-oncogene cKIT receptor. Combination with other modalities such as stereotactic body radiation therapy, therapeutic vaccines, and checkpoint inhibitors is being pursued for improved efficacy. PMID- 27660469 TI - Polymorphisms in the XPC gene and gastric cancer susceptibility in a Southern Chinese population. AB - Previous studies have reported that XPC gene polymorphisms may modify the individual susceptibility to gastric cancer. In this case-control study with a total of 1,142 cases and 1,173 controls, four potentially functional polymorphisms were genotyped in the XPC gene (rs2228001 A>C, rs2228000 C>T, rs2607775 C>G, and rs1870134 G>C) by Taqman assays and their associations were analyzed with the risk of gastric cancer in a Southern Chinese population. No significant association between any of XPC polymorphisms and gastric cancer risk was detected except for a borderline association with the rs2228000 CT/TT genotype (crude odds ratio =0.86, 95% confidence interval =0.73-1.02, P=0.088) when compared to the rs2228000 CC genotype. Further stratified analysis revealed that the protective effect of rs2228000 CT/TT on the risk of gastric cancer was only significant among subjects older than 58 years. In summary, results indicated that genetic variations in XPC gene may play a weak effect on gastric cancer susceptibility in Southern Chinese population, which warrants further confirmation in larger prospective studies with different ethnic populations. PMID- 27660471 TI - Novel chlorambucil-conjugated anionic linear-globular PEG-based second-generation dendrimer: in vitro/in vivo improved anticancer activity. AB - Evaluating the efficacy of anticancer drugs is an evolving and research-oriented issue. The objective of this study was to reduce the insolubility of chlorambucil (CBL) in water and improve the anticancer activity of CBL in vitro and in vivo through the conjugation of CBL with anionic linear-globular dendrimer (second generation, G2). In the current study, the anticancer activity among three groups that include CBL, CBL-G2 dendrimer, and control was measured in vitro and in vivo. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol based dendrimer, which conjugated to the CBL exterior through an ester linkage, was able to significantly improve the treatment efficacy over clinical CBL alone with respect to proliferation assay, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H tetrazolium-5-carboxanilide; half maximal inhibitory concentration (IC50) was calculated to be 141 ug/mL for CBL alone and 27.7 ug/mL for CBL-G2 dendrimer; P<0.05. In addition, CBL-G2 dendrimer conjugate forestalled the growth of MCF-7 cancerous cells in addition to enhancing the number of apoptotic and necrotic cells as demonstrated by an annexin V-fluorescein isothiocyanate assay. CBL-G2 dendrimer conjugate was able to checkmate antiapoptotic Bcl-2 expression and Bcl 2/Bax ratio in a large scale compared with the control group and CBL alone (P<0.005). In vivo studies showed that tumor treatment by CBL-G2 dendrimer conjugate outstrips the efficacy of treatment compared with CBL alone. The evaluation was based on reduction in tumor volume and tumor growth inhibition of murine 4T1 mammary tumor cells. Tumor volume of 140%+/-8% was measured in the treatment with CBL-G2 dendrimer, whereas 152%+/-13.5% was calculated in the treatment with free CBL (P<0.05). However, there were no significant differences in histological assay among the three groups. In conclusion, tumor growth suppression potential of CBL-G2 dendrimer, which was assessed in both in vitro and in vivo experiments, has provided empirical evidence to buttress the fact that this compound could be considered for functional cancer treatment with low side effects. PMID- 27660470 TI - Incidence and mortality rates in breast, corpus uteri, and ovarian cancers in Poland (1980-2013): an analysis of population-based data in relation to socioeconomic changes. AB - OBJECTIVES: This study aimed to analyze incidence and mortality trends in breast cancer (BC), corpus uteri cancer (CUC), and ovarian cancer (OC) in Poland in the context of sociodemographic changes. MATERIALS AND METHODS: Incidence and mortality data (1980-2013) were retrieved from the Polish National Cancer Registry, while socioeconomic data (1960-2013) were obtained from the World Bank. Age-standardized incidence and mortality rates were calculated by direct standardization, and join-point regression was performed to describe trends using the average annual percentage change (AAPC). RESULTS: A significant decrease in birth and fertility rates and a large increase in gross domestic product were observed together with a decrease in the total mortality rate among women, as well as an increase in life expectancy for women. A large, significant increase in BC incidence was observed (AAPC1980-1990 2.14, AAPC1990-1996 4.71, AAPC1996 2013 2.21), with a small but significant decrease in mortality after a slight increase (AAPC1980-1994 0.52, AAPC1994-2013 -0.66). During the period 1980-2013, a significant increase in CUC incidence (AAPC1980-1994 3.7, AAPC1994-2013 1.93) was observed, with an initial mortality-rate reduction followed by a significant increase (AAPC1980-2006 -1.12, AAPC2006-2013 3.74). After the initial increase of both OC incidence and mortality from 1994, the incidence rate decreased significantly (AAPC1980-1994 2.98, AAPC1994-2013 -0.49), as did the mortality rate (AAPC1980-1994 0.52, AAPC1994-2013 -0.66). CONCLUSION: After 1994, a decrease in OC incidence was found, while the incidence of BC and CUC continued to increase. A reduction in mortality rate was observed for BC and OC predominantly at the end of the study period, while for CUC, after a long decreasing mortality trend, a significant increase was observed. PMID- 27660472 TI - The clinical effects of low-dose splenic irradiation combined with chest three dimensional conformal radiotherapy on patients with locally advanced non-small cell lung cancer: a randomized clinical trial. AB - OBJECTIVE: The objective of this study was to explore the clinical effects of low dose splenic irradiation on locally advanced non-small-cell lung cancer (NSCLC) patients. METHODS: Thirty-eight patients with stage III NSCLC were randomly divided into a control group and a combined treatment group. The control group only received chest three-dimensional conformal radiotherapy, while the combined treatment group received low-dose splenic irradiation followed by chest three dimensional conformal radiotherapy after 6 hours. T lymphocyte subsets of the blood cells were tested before, during, and after treatment once a week. The side effects induced by radiation were observed, and a follow-up was done to observe the survival statistics. RESULTS: The ratio differences in CD4(+) cells, CD8(+) cells, and CD4(+)/CD8(+) before and after treatment were not statistically significant (P>0.05) in both the groups. The immune indexes were also not statistically significant (P>0.05) before and after radiotherapy in the combined treatment group. However, the numbers of CD4(+) cells and CD4(+)/CD8(+) ratios before radiotherapy were higher than after radiotherapy in the control group. There were no differences in the incidence of radiation toxicities between the two groups; however, the incidence of grade III or IV radiation toxicities was lower, and the dose at which the radiation toxicities appeared was higher in the combined treatment group. The total response rate was 63.16% (12/19) in the combined treatment group vs 42.11% (8/19) in the control group. The median 2-year progression-free survival (15 months in the combined treatment group vs 10 months in the control group) was statistically significant (P<0.05). The median 2-year overall survival (17.1 months in the combined treatment group vs 15.8 months in the control group) was not statistically significant (P>0.05). CONCLUSION: Low dose radiation can alleviate the radiation toxicities, improve the short-term efficacy of radiotherapy, and improve the survival of locally advanced NSCLC patients. PMID- 27660473 TI - Phosphoglycerate dehydrogenase is a novel predictor for poor prognosis in gastric cancer. AB - PURPOSE: Phosphoglycerate dehydrogenase (PHGDH) acts as a key metabolic enzyme in the rate-limiting step in serine biosynthesis and plays an important role in metastasis of several cancers. The aim of this study was to investigate the prognostic value of PHGDH in gastric cancer (GC). METHODS: The messenger RNA expression of PHGDH was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of PHGDH was performed on tissue microarray, composed of 482 GC and 64 matched adjacent nontumor tissues acquired from surgery, 20 chronic gastritis, 18 intestinal metaplasia, and 31 low-grade and 66 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsy. Univariate and multivariate Cox proportional hazard models were used to perform survival analyses. RESULTS: Both PHGDH messenger RNA and protein product exhibited GC tissue-preferred expression, when compared with benign tissues. The high PHGDH expression was significantly correlated with histological type (P=0.011), tumor stage (P=0.014), and preoperative carcinoembryonic antigen (P<0.001). A negative correlation was found between PHGDH expression and the 5-year survival rate of patients with GC. Furthermore, multivariate analysis indicated that PHGDH was an independent prognostic factor for outcome in GC. CONCLUSION: PHGDH is important in predicting patient outcomes and is a potential target for the development of therapeutic approaches to GC. PMID- 27660474 TI - Accelerated partial breast irradiation in an Asian population: dosimetric findings and preliminary results of a multicatheter interstitial program. AB - INTRODUCTION: Accelerated partial breast irradiation (APBI) using the multicatheter method has excellent cosmesis and low rates of long-term toxicity. However, there are few studies looking at the feasibility of this procedure and the outcomes in an Asian population. This study aims to look at outcomes at our hospital. METHODS: We identified 121 patients treated with APBI at our center between 2008 and 2014. The median follow-up for our patient group was 30 months (range 3.7-66.5). The prescribed dose per fraction was 3.4 Gy in 10 fractions. In this study population, 71% of the patients were Chinese while 15% (n=19) were of other Asian ethnicity. RESULTS: In this study, the median breast volume was 850 cc (range 216-2,108) with 59.5% (n=72) patients with a breast volume of <1,000 cc. The average planning target volume was 134 cc (range 28-324). The number of catheters used ranged from 8 to 25 with an average of 18 catheters used per patient. We achieved an average dose homogeneity index of 0.76 in our patients. The average D90(%) was 105% and the average D90(Gy) was 3.6 Gy per fraction. The median volume receiving 100% of the prescribed dose (V100) was 161.7 cc (range 33.9-330.1), 150% of the prescribed dose (V150) and 200% of the prescribed dose (V200) was 39.4 cc (range 14.6-69.6) and 14.72 cc (range 6.48-22.25), respectively. Our dosimetric outcomes were excellent even in patients with breast volume under 1,000 cc. There were no cases of grade 3 skin toxicity or acute pneumonitis. Two patients had a postoperative infection and two patients had fat necrosis postprocedure. CONCLUSION: Multicatheter high dose rate APBI is a safe and feasible procedure that can be carried out with minimal toxicity in Asian patients with breast volumes under 1,000 cc. PMID- 27660475 TI - The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis. AB - Breast cancer (BC) is the most common female malignancy within the spectrum of human cancer. One promising way to reduce the mortality and morbidity of BC is to explore novel diagnostic markers for early diagnosis and prognostication. The neutrophil lymphocyte ratio (NLR) is a good reflection of inflammation, which plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear. The aim of this meta analysis is to explore the prognostic value of NLR in BC. Among the screened references in the database, 12 eligible studies were identified in this study. Patients with a higher NLR had a shorter disease-free survival (hazard ratio =1.46, 95% confidence interval: 1.12-1.90, P=0.044) and overall survival (hazard ratio =2.03, 95% confidence interval: 1.41-2.93, P<0.001). In the subgroup analysis of NLR and disease-free survival, the studies from Eastern countries had a positive result with perfect homogeneity (I (2)=0); however, this homogeneity has not been achieved in studies from Western countries. In the subgroup analysis of the NLR and overall survival, the results of the univariate and multivariate analyses were completely different, with different heterogeneity. In the luminal A and luminal B subtypes, we found that there was no association between the NLR and overall survival in the BC patients. Positive results were obtained in the analyses of the human epidermal growth factor receptor 2 (HER2)-positive and triple-negative BC subtypes. In conclusion, this meta-analysis suggests that NLR is a good prognostic marker for BC, and patients with a higher NLR have poorer prognoses. Future studies should perform more detailed investigations to decrease heterogeneity and determine the appropriate cut-off values for different races. PMID- 27660476 TI - A budget impact analysis of Spiromax((r)) compared with Turbuhaler((r)) for the treatment of moderate to severe asthma: a potential improvement in the inhalation technique to strengthen medication adherence could represent savings for the Spanish Healthcare System and five Spanish regions. AB - OBJECTIVE: To assess the economic impact of the introduction of DuoResp((r)) Spiromax((r)) by focusing on a potential improvement in the inhalation technique to strengthen medication adherence for the treatment of moderate to severe asthmatics in Spain and five Spanish regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. METHODS: A 4-year budget impact model was developed for the period 2015-2018 from the Spanish Healthcare System perspective. Budesonide-formoterol fixed-dose combination delivered by Turbuhaler((r)) was considered to be the most appropriate comparator for assessing the budget impact with the introduction of DuoResp((r)) Spiromax((r)). National and regional data on asthma prevalence were obtained from the literature. Input parameters on health care resources were obtained by consulting experts from different Spanish hospitals. Resources used included medical visits, emergency room visits, and hospitalizations. The average numbers of primary care and specialist visits per year were also gathered. Based on health care resource use per patient, the total treatment cost per patient was estimated. RESULTS: The population with moderate to severe asthma treated with budesonide-formoterol fixed-dose combinations delivered by Turbuhaler((r)) in 2015 was estimated to be 166,985 in Spain. Region-specific prevalence data resulted in 25,081, 12,392, 16,097, 17,829, and 15,148 patients in Andalusia, Catalonia, Galicia, Madrid, and Valencia, respectively. Based on the forecast uptake of DuoResp((r)) Spiromax((r)), the total budget savings in Spain were expected to be ?1.509 million over the next 4 years. Region-specific rates imply that the total savings were expected to be ?229,706 in Andalusia, ?90,145 in Catalonia, ?188,327 in Galicia, ?122,669 in Madrid, and ?165,796 in Valencia over 2015-2018. CONCLUSION: The introduction of DuoResp((r)) Spiromax((r)), which represents a potential improvement in the inhalation technique to strengthen medication adherence for the treatment of moderate to severe asthma, could represent savings for the Spanish National Health Society and five Spanish regions. PMID- 27660477 TI - Effect of the multifunctional cosmetic ingredient sphinganine on hair loss in males and females with diffuse hair reduction. AB - Sphingolipids are well known to promote keratinocyte differentiation and to induce ceramide production. In addition, they show anti-inflammatory and antimicrobial activities. Thus, the aim of this study is to investigate the potential effect of sphinganine on prolonging the hair anagen rate and improving the overall hair quality and scalp health. The inhibitory potential of sphinganine toward 5-alpha-reductase was studied using an in vitro assay. The stimulation of the antimicrobial peptide HBD2 by sphinganine was measured by real time polymerase chain reaction and immunostaining. Sphinganine bioavailability was studied ex vivo using a pig skin model. A placebo-controlled, double-blind study was designed to evaluate the efficacy of sphinganine on hair loss and hair/scalp quality in vivo. In vitro results showed that sphinganine is a potent inhibitor of 5-alpha-reductase type I that prevents the conversion of testosterone to dihydrotestosterone, a key factor of androgenetic male baldness. In vivo results demonstrated efficacy in reducing non-illness-related hair loss among males. In terms of expert rating, all hair quality and scalp parameters improved after application of sphinganine. Improved scalp health might be linked to the observed increase of the antimicrobial peptide HBD2. Thus, sphinganine is well suited as a topical alternative for the improvement of scalp health and hair quality and anti-hair loss application. PMID- 27660478 TI - Preliminary study on the development of an antistretch marks water-in-oil cream: ultrasound assessment, texture analysis, and sensory analysis. AB - PURPOSE: Striae distensae represent the result of the failure of the dermis to sustain intrinsic mechanical forces. Intensive moisturization of the lesions and use of emollient oils have been recommended for the prevention and treatment of striae distensae rubra. The aim of this research was to formulate an emollient water-in-oil cosmetic cream containing argan oil, which may be helpful in the prevention or early treatment of striae distensae. PATIENTS AND METHODS: Sensory evaluation of the consistency, firmness, adhesiveness, oiliness, spreadability, and rapidity of penetration into the skin was evaluated by 22 volunteers using 10 point scales for each descriptor. The instrumental characterization of the cream was performed using Brookfield((r)) CT3 Texture Analyzer. The cutaneous changes induced by the topical use of the cream were evaluated by assessing the thickness of the epidermis, hydration, and elasticity of the skin using DermaLab((r)) Combo scanner. RESULTS: Ultrasound measurements showed an improvement in the elasticity of the epidermis following the application of cream. The product was well tolerated and appreciated by the consumers in terms of its spreadability, penetration ability, and lack of stickiness. The values recorded for texture analysis were firmness 10.16+/-0.15 mJ, adhesiveness 30.94+/-6.87 g, consistency 1229.50+/-119.78 g, spreadability 481.50+/-39 g, and stringiness 0.56+/-0.09 mJ. CONCLUSION: A water-in-oil cream containing argan oil and emollient ingredients with appropriate physical characteristics was obtained. In vivo study of clinical efficacy revealed a positive effect on increasing the skin elasticity, suggesting that the cream may be helpful in the prevention or early treatment of striae distensae. PMID- 27660479 TI - Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review. AB - BACKGROUND: Cohesive monophasic polydensified fillers show unique viscoelastic properties and variable density of hyaluronic acid, allowing for a homogeneous tissue integration and distribution of the material. OBJECTIVE: The aim of this paper was to review the clinical data regarding the performance, tolerability, and safety of the Belotero((r)) fillers for soft-tissue augmentation and rejuvenation. METHODS: A literature search was performed up until May 31, 2015 to identify all relevant articles on Belotero((r)) fillers (Basic/Balance, Hydro, Soft, Intense, Volume) and equivalent products (Esthelis((r)), Mesolis((r)), Fortelis((r)), Modelis((r))). RESULTS: This comprehensive review included 26 papers. Findings from three randomized controlled trials showed a greater reduction in nasolabial fold severity with Belotero((r)) Basic/Balance than with collagen (at 8, 12, 16, and 24 weeks, n=118) and Restylane((r)) (at 4 weeks, n=40), and higher patient satisfaction with Belotero((r)) Intense than with Perlane((r)) (at 2 weeks, n=20). With Belotero((r)) Basic/Balance, an improvement of at least 1 point on the severity scale can be expected in ~80% of patients 1-6 months after injection, with an effect still visible at 8-12 months. Positive findings were also reported with Belotero((r)) Volume (no reduction in hyaluronic acid volume at 12 months, as demonstrated by magnetic resonance imaging), Soft (improvement in the esthetic outcomes when used in a sequential approach), and Hydro (improvement in skin appearance in all patients). The most common adverse effects were mild-to-moderate erythema, edema, and hematoma, most of which were temporary. There were no reports of Tyndall effect, nodules, granulomas, or tissue necrosis. CONCLUSION: Clinical evidence indicates sustainable esthetic effects, good safety profile, and long-term tolerability of the Belotero((r)) fillers, particularly Belotero((r)) Basic/Balance and Intense. PMID- 27660481 TI - Combining genetic and evolutionary engineering to establish C4 metabolism in C3 plants. AB - To feed a world population projected to reach 9 billion people by 2050, the productivity of major crops must be increased by at least 50%. One potential route to boost the productivity of cereals is to equip them genetically with the 'supercharged' C4 type of photosynthesis; however, the necessary genetic modifications are not sufficiently understood for the corresponding genetic engineering programme. In this opinion paper, we discuss a strategy to solve this problem by developing a new paradigm for plant breeding. We propose combining the bioengineering of well-understood traits with subsequent evolutionary engineering, i.e. mutagenesis and artificial selection. An existing mathematical model of C3-C4 evolution is used to choose the most promising path towards this goal. Based on biomathematical simulations, we engineer Arabidopsis thaliana plants that express the central carbon-fixing enzyme Rubisco only in bundle sheath cells (Ru-BSC plants), the localization characteristic for C4 plants. This modification will initially be deleterious, forcing the Ru-BSC plants into a fitness valley from where previously inaccessible adaptive steps towards C4 photosynthesis become accessible through fitness-enhancing mutations. Mutagenized Ru-BSC plants are then screened for improved photosynthesis, and are expected to respond to imposed artificial selection pressures by evolving towards C4 anatomy and biochemistry. PMID- 27660480 TI - Using genomic information to improve soybean adaptability to climate change. AB - Climate change has brought severe challenges to agriculture. It is anticipated that there will be a drop in crop yield - including that of soybean - due to climatic stress factors that include drastic fluctuations in temperature, drought, flooding and high salinity. Genomic information on soybean has been accumulating rapidly since initial publication of its reference genome, providing a valuable tool for the improvement of cultivated soybean. Not only are many molecular markers that are associated with important quantitative trait loci now identified, but we also have a more detailed picture of the genomic variations among soybean germplasms, enabling us to utilize these as tools to assist crop breeding. In this review, we will summarize and discuss the currently available soybean genomic approaches, including whole-genome sequencing, sequencing-based genotyping, functional genomics, proteomics, and epigenomics. The information uncovered through these techniques will help further pinpoint important gene candidates and genomic loci associated with adaptive traits, as well as achieving a better understanding of how soybeans cope with the changing climate. PMID- 27660482 TI - C3 cotyledons are followed by C4 leaves: intra-individual transcriptome analysis of Salsola soda (Chenopodiaceae). AB - Some species of Salsoleae (Chenopodiaceae) convert from C3 photosynthesis during the seedling stage to the C4 pathway in adult leaves. This unique developmental transition of photosynthetic pathways offers the exceptional opportunity to follow the development of the derived C4 syndrome from the C3 condition within individual plants, avoiding phylogenetic noise. Here we investigate Salsola soda, a little-studied species from tribe Salsoleae, using an ontogenetic approach. Anatomical sections, carbon isotope (delta13C) values, transcriptome analysis by means of mRNA sequencing, and protein levels of the key C4 enzyme phosphoenolpyruvate carboxylase (PEPC) were examined from seed to adult plant stages. Despite a previous report, our results based on delta13C values, anatomy and transcriptomics clearly indicate a C3 phase during the cotyledon stage. During this stage, the entire transcriptional repertoire of the C4 NADP-malic enzyme type is detected at low levels compared to a significant increase in true leaves. In contrast, abundance of transcripts encoding most of the major photorespiratory enzymes is not significantly decreased in leaves compared to cotyledons. PEPC polypeptide was detected only in leaves, correlating with increased PEPC transcript abundance from the cotyledon to leaf stage. PMID- 27660485 TI - Streptococcus pneumoniae sepsis as the initial presentation of systemic lupus erythematosus. AB - OBJECTIVE: Infections are among the most important causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE) but are rare initial presentation of the disease. Therefore, in this study, we describe a case of Streptococcus pneumoniae sepsis in a young woman with previously undiagnosed SLE. CASE REPORT: A 23-year-old female patient was admitted to our outpatient clinic complaining of high fever (40 degrees C), chills, fatigue, generalized myalgia, and cough with brown sputum for 5 days. Blood cultures grew gram positive coccus defined as S. pneumoniae using standard procedures. Antinuclear antibody was positive at a titer of 1/1,000, and anti-double-stranded DNA was positive at 984 IU/mL. She was diagnosed with SLE. Her respiratory symptoms and pleural effusion were considered to be due to pulmonary manifestation of SLE. CONCLUSION: The underlying immunosuppression caused by SLE could have predisposed the patient to invasive pneumococcal disease. It may also occur as a primary presenting feature, although a rare condition. PMID- 27660484 TI - The genetics of uveal melanoma: current insights. AB - Uveal melanoma (UM) is the most common malignant eye tumor in adults affecting ~7,000 individuals per year worldwide. UM is a rare subtype of melanoma with distinct clinical and molecular features as compared to other melanoma subtypes. UMs lack the most typical cutaneous melanoma-associated mutations (BRAF, NRAS, and NF1) and are instead characterized by a different set of genes with oncogenic or loss-of-function mutations. By next-generation sequencing efforts on UM tumors, several driver genes have been detected. The most frequent ones are BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. In many cases, mutations in these genes appear in a mutually exclusive manner, have different risk of metastasis, and are consequently of prognostic importance. The majority of UM cases are sporadic but a few percentage of the cases occurs in families with an inherited predisposition for this malignancy. In recent years, germline mutations in the BAP1 gene have been found to segregate in an autosomal dominant pattern with numerous different cancer types including UM in cancer-prone families. This cancer syndrome has been denoted as the tumor predisposition syndrome. PMID- 27660486 TI - Prognostic value of quantitative sensory testing in low back pain: a systematic review of the literature. AB - Quantitative sensory testing (QST) measures have recently been shown to predict outcomes in various musculoskeletal and pain conditions. The aim of this systematic review was to summarize the emerging body of evidence investigating the prognostic value of QST measures in people with low back pain (LBP). The protocol for this review was prospectively registered on the International Prospective Register of Systematic Reviews. An electronic search of six databases was conducted from inception to October 2015. Experts in the field were contacted to retrieve additional unpublished data. Studies were included if they were prospective longitudinal in design, assessed at least one QST measure in people with LBP, assessed LBP status at follow-up, and reported the association of QST data with LBP status at follow-up. Statistical pooling of results was not possible due to heterogeneity between studies. Of 6,408 references screened after duplicates removed, three studies were finally included. None of them reported a significant association between the QST measures assessed and the LBP outcome. Three areas at high risk of bias were identified which potentially compromise the validity of these results. Due to the paucity of available studies and the methodological shortcomings identified, it remains unknown whether QST measures are predictive of outcome in LBP. PMID- 27660483 TI - Functional characterization of the Arabidopsis transcription factor bZIP29 reveals its role in leaf and root development. AB - Plant bZIP group I transcription factors have been reported mainly for their role during vascular development and osmosensory responses. Interestingly, bZIP29 has been identified in a cell cycle interactome, indicating additional functions of bZIP29 in plant development. Here, bZIP29 was functionally characterized to study its role during plant development. It is not present in vascular tissue but is specifically expressed in proliferative tissues. Genome-wide mapping of bZIP29 target genes confirmed its role in stress and osmosensory responses, but also identified specific binding to several core cell cycle genes and to genes involved in cell wall organization. bZIP29 protein complex analyses validated interaction with other bZIP group I members and provided insight into regulatory mechanisms acting on bZIP dimers. In agreement with bZIP29 expression in proliferative tissues and with its binding to promoters of cell cycle regulators, dominant-negative repression of bZIP29 altered the cell number in leaves and in the root meristem. A transcriptome analysis on the root meristem, however, indicated that bZIP29 might regulate cell number through control of cell wall organization. Finally, ectopic dominant-negative repression of bZIP29 and redundant factors led to a seedling-lethal phenotype, pointing to essential roles for bZIP group I factors early in plant development. PMID- 27660487 TI - OxyContin was submitted and justifiably approved by the agency as a 12-hour dosage form. PMID- 27660488 TI - Brain imaging of pain: state of the art. AB - Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain's role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained. PMID- 27660489 TI - Relationship between self-reported pain sensitivity and pain after total knee arthroplasty: a prospective study of 71 patients 8 weeks after a standardized fast-track program. AB - BACKGROUND AND PURPOSE: This was a prospective cohort study assessing data from 71 adult patients undergoing total knee arthroplasty (TKA) following a standardized fast-track program between January and July 2013. The objective was to examine the relationship between self-rated pain sensitivity, as measured by the Pain Sensitivity Questionnaire (PSQ), and postoperative pain after TKA. METHODS: The baseline questionnaires, PSQ and Brief Pain Inventory, were given to the patients for self-administration at the presurgical evaluation (1-2 weeks prior to surgery). The follow-up questionnaire, Brief Pain Inventory, was administered at the first follow-up, 8 weeks after surgery. RESULTS: A statistically significant association was found between average preoperative pain and average pain 8 weeks after surgery (P=0.001). The PSQ-minor was statistically significantly associated with average pain only for patients younger than 70 years (P=0.03). INTERPRETATION: This is the first study to examine the relationship between pain sensitivity measured by PSQ and postoperative pain in patients after TKA. We found that a lower score on the PSQ-minor was statistically significantly associated with patients' pain 8 weeks after TKA surgery, but only for younger patients. Further research is needed to explore whether the PSQ could be a useful screening tool for patients' pain sensitivity in clinical settings. PMID- 27660491 TI - Five-year risk of HIV diagnosis subsequent to 147 hospital-based indicator diseases: a Danish nationwide population-based cohort study. AB - BACKGROUND: It has been suggested that targeted human immunodeficiency virus (HIV) testing programs are cost-effective in populations with an HIV prevalence >0.1%. Several indicator diseases are known to be associated with increased risk of HIV infection, but estimates of HIV frequency in persons with relevant indicator diseases are nonexistent. METHODS: In a nationwide population-based cohort study encompassing all Danish residents aged 20-60 years during 1994-2013, we estimated the 5-year risk of an HIV diagnosis (FYRHD) after a first-time diagnosis of 147 prespecified potential indicator diseases. To estimate the risk of HIV diagnosis in the general population without any indicator diseases, we calculated the FYRHD starting at age 25, 35, 45, and 55 years. RESULTS: The risk in the male general population was substantially higher than the female general population, and the risk was lower in the older age categories. Individuals of African origin had a higher FYRHD than individuals of Danish origin. A number of diseases were identified with a FYRHD >0.1%, with infectious diseases, such as syphilis, hepatitis, and endocarditis, associated with a particularly high FYRHD. Other potential indicator diseases, such as most urologic, nephrologic, rheumatologic, and endocrine disorders were generally associated with a low FYRHD. CONCLUSION: Our study identified a large number of indicator diseases associated with a FYRHD >0.1%. These data can be used as a tool for planning targeted HIV screening programs. PMID- 27660490 TI - Association between Global Assessment of Functioning scores and indicators of functioning, severity, and prognosis in first-time schizophrenia. AB - BACKGROUND: Assessment of psychosocial functioning in people with schizophrenia is important. The Global Assessment of Functioning (GAF-F) scale represents a widely applied, easy, and quick tool, but its validity and reliability have been debated. The aim was to investigate whether GAF-F scores are associated with other indicators of functioning, severity, and hospitalization. METHODS: A Danish population-based cohort study of adults (>=18 years) with a recorded GAF-F score at first-time schizophrenia diagnosis during 2004-2011 was performed. The internal validity of GAF-F was evaluated by assessing its association with other baseline measures of functioning and illness severity. Risk of schizophrenia hospitalization within 2 years was evaluated using Cox regression stratified by sex and adjusted for age, year of diagnosis, and inpatient/outpatient status at diagnosis. RESULTS: We identified 2,837 cases of schizophrenia with a GAF-F score at first-time diagnosis (73.0% inpatients; 62.6% males). GAF-F was associated with several baseline measures of functioning and illness severity, such as female sex, being in work, and a longer baseline hospitalization. Lower GAF-F scores were associated with higher hospitalization risk among males (reference GAF-F 61-100): GAF-F 51-60: hazard rate ratio (HRR) =1.24 (95% confidence interval [CI] =0.89-1.75); GAF-F 41-50: HRR =1.31 (95% CI =0.97-1.77); GAF-F 31 40: HRR =1.36 (95% CI =1.01-1.82); GAF-F 21-30: HRR =1.50 (95% CI =1.09-2.06); and GAF-F 1-20: HRR =2.30 (95% CI =1.36-3.90), fitting a dose-response relationship (P=0.031). This association was not found in females. CONCLUSION: GAF-F at first-time schizophrenia diagnosis showed good internal validity against other measures of functionality in a Danish hospital setting. Severe impairment (as measured by the GAF-F score) at first-time schizophrenia diagnosis was associated with a higher risk of 2-year hospitalization among males, which may indicate sex differences in the course of disease and treatment response. PMID- 27660492 TI - Experiences of social support among women presenting for obstetric fistula repair surgery in Tanzania. AB - OBJECTIVE: An obstetric fistula is a childbirth injury resulting in uncontrollable leakage of urine and/or feces and can lead to physical and psychological challenges, including social isolation. Prior to and after fistula repair surgery, social support can help a woman to reintegrate into her community. The aim of this study was to preliminarily examine the experiences of social support among Tanzanian women presenting with obstetric fistula in the periods immediately preceding obstetric fistula repair surgery and following reintegration. PATIENTS AND METHODS: The study used a mixed-methods design to analyze cross-sectional surveys (n=59) and in-depth interviews (n=20). RESULTS: Women reported widely varying levels of social support from family members and partners, with half of the sample reporting overall high levels of social support. For women experiencing lower levels of support, fistula often exacerbated existing problems in relationships, sometimes directly causing separation or divorce. Many women were assertive and resilient with regard to advocating for their fistula care and relationship needs. CONCLUSION: Our data suggest that while some women endure negative social experiences following an obstetric fistula and require additional resources and services, many women report high levels of social support from family members and partners, which may be harnessed to improve the holistic care for patients. PMID- 27660494 TI - A randomized controlled trial of a videoconferencing smoking cessation intervention for Korean American women: preliminary findings. AB - INTRODUCTION: Korean women are reluctant to pursue in-person smoking cessation treatment due to stigma attached to women smokers and prefer treatment such as telephone and online smoking cessation programs that they can access secretively at home. However, there is some evidence that face-to-face interaction is the most helpful intervention component for them to quit smoking. METHODS: This study is a pilot clinical trial that examined the acceptability and feasibility of a videoconferencing smoking cessation intervention for Korean American women and compared its preliminary efficacy with a telephone-based intervention. Women of Korean ethnicity were recruited nationwide in the United States and randomly assigned at a ratio of 1:1 to either a video arm or a telephone arm. Both arms received eight 30-minute weekly individualized counseling sessions of a deep cultural smoking cessation intervention and nicotine patches for 8 weeks. Participants were followed over 3 months from the quit day. RESULTS: The videoconferencing intervention was acceptable and feasible for Korean women aged <50 years, whereas it was not for older women. Self-reported abstinence was high at 67% and 48% for the video and telephone arm at 1 month post-quit, respectively. The rates declined to 33% for the video arm and 28% for the telephone arm at 3 months post-quit when salivary cotinine test was performed. CONCLUSION: Findings support that both videoconferencing and telephone counseling can be effective, and personal preference is likely an important factor in treatment matching. The deep cultural smoking cessation intervention may account for the outcomes of telephone counseling being better than prior studies in the literature for Korean women. PMID- 27660495 TI - Atypical oculopalatal tremor as the presentation of vertebral artery dolichoectasia. AB - Vertebrobasilar dolichoectasia (VBD) is a rare dilative arteriopathy defined as elongation or widening of the intracranial vertebral and/or basilar arteries. The prevalence ranges from 0.06% to 5.8%. The majority of VBDs are asymptomatic. Downbeat nystagmus has been reported as a component of an infrequent ocular movement disorder in VBD. Nevertheless, oculopalatal tremor (OPT), delayed sequelae of a brainstem lesion, has never been demonstrated in VBD cases. Synchronized rhythmic involuntary contractions of the soft palate with an ocular pendular nystagmus, predominantly vertical pendular nystagmus, are the hallmark presentation. Our case demonstrated a 50-year-old female who presented with 3 month history of oscillopsia. Examination showed binocular conjugate torsional jerk nystagmus simultaneous with a contraction of the soft palate, defined as an atypical OPT, resulting from dolichoectatic left vertebral artery compressing on medulla, demonstrated by magnetic resonance imaging. Bilateral conjugate torsional jerk nystagmus simultaneous with palatal tremor, considering as an atypical OPT, should be included as one of the symptomatic presentations of vertebral artery dolichoectasia in spite of its rarity. PMID- 27660493 TI - Pregnancy in women with thalassemia: challenges and solutions. AB - Advances in treatment of thalassemia have led to the aging of thalassemic patients, and consequently concern about successful reproductive outcome is augmented. Although women with thalassemia intermedia only were considered competent of achieving pregnancy, case series reveal the willingness of both thalassemia major and thalassemia intermedia women to have a family. Pregnancy in general is characterized by dynamic multiple-system changes and increased susceptibility to oxidative stress, while homozygous, transfusion-dependent, beta thalassemia patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload and thalassemia intermedia, usually nontransfused, is associated with augmented risk of thromboembolic events. Pregnancy in thalassemia should be considered a high risk for both mother and fetus, and favorable outcomes are the result of continuous preconception, antenatal, and postpartum assessment and management by a team of thalassemia experts. PMID- 27660496 TI - Acceptance of a reusable self-injection device for recombinant human growth hormone: final data from a questionnaire-based, cross-sectional, international, multicenter, observational study in pediatric patients. AB - BACKGROUND: A questionnaire-based survey was conducted to assess attitudes toward a reusable self-injection system (SurePalTM) among pediatric patients with growth disturbances who were prescribed treatment with Omnitrope((r)) within routine clinical practice. METHODS: This was a multicenter, observational study, incorporated into the noninterventional PAtients TReated with Omnitrope((r)) (PATRO) Children study. Included subjects, or their caregivers, completed a questionnaire on the following five main areas: attractiveness of SurePalTM, training received, using the device, the low drug wastage system, and experience versus other devices used previously (pretreated patients). Responses were based on a 5-point scale, with 2 being the best possible outcome and -2 the worst possible outcome. RESULTS: In total, 550 patients were included in this study (338 from France, 169 from Germany, and 43 from the UK). The mean age +/- standard deviation of participants was 10.8+/-3.5 years; the majority (57%) were male and growth hormone treatment naive (88%). Almost half (49.8%) of children prepared their SurePalTM for injection themselves and 45.5% performed injections themselves. As patients progressed into their teens, the majority (>=75%) favored preparing SurePalTM and performing injections themselves, rather than seeking assistance. The attractiveness of SurePalTM was rated as excellent/good by 84.7% of patients overall; this rating was similarly high (>=79%) across countries and age-groups. Preparing (88.8%) and using (83.3%) SurePalTM were rated as very easy/easy by most patients; these ratings were similarly high, irrespective of country or age-group. The dose-memory function was rated as very helpful/helpful by 66.2% of patients. Among 246 patients who reported using the low drug-waste feature, 87.4% found it helpful. Among pretreated patients (n=64), 78.2% reported that SurePalTM was much better/better than their previous device. CONCLUSION: These data confirm the ease of use and patient preference for SurePalTM among pediatric patients with growth disturbances. PMID- 27660497 TI - Study on Expression Modes and Cleavage Role of miR156b/c/d and its Target Gene Vv SPL9 During the Whole Growth Stage of Grapevine. AB - miR156 regulates the expression of its target SPL (PROMOTER BINDING-LIKE) genes during flower and fruit development, diverse developmental stage transitions, especially from vegetative to reproductive growth phases, by cleaving the target mRNA SPL of one plant-specific transcription factor. However, systematic reports on grapevine have yet to be presented. Here, the precise sequence of miR156 (vvi miR156b/c/d) in grapevine "Takatsuma" was cloned with a previously cloned grapevine SPL (Vv-SPL9). Expression profiles in 18 grapevine tissues were identified through stem-loop RT-PCR. The interaction mode between vvi-miR156b/c/d and Vv-SPL9 was further validated by detecting the cleavage site and cleavage products of 3'- and 5'-ends via an integrated approach of 5'-RLM-RACE (RNA ligase mediated 5'-rapid amplification of cDNA ends), 3'-PPM-RACE (poly(A) polymerase mediated 3'-rapid amplification of cDNA ends), and qRT-PCR (real time reverse transcriptase-polymerase chain reaction). The variation in their cleavage roles in the whole growth stage of grapevine was also systematically investigated. Results showed that vvi-miR156b/c/d exhibited typical temporal-spatial-specific expression levels. The expression levels were higher in vegetative organs, such as leaf, than in reproductive organs, such as tendrils, flowers, and berries. A significant variation was observed during vegetative-to-reproductive transition. The expression patterns of Vv-SPL9 showed the opposite trends with those of vvi miR156b. We confirmed that the cleavage site was at the 10th site of vvi miR156b/c/d complementary to Vv-SPL9 in "Takatsuma" grapevine. We also identified the temporal-spatial variation of the cleavage products. This variation can indicate the regulatory function of miR156 on SPL in grapevines. Our findings provide further insights into the functions of vvi-miR156b/c/d and its target Vv SPL9, and also help enrich our knowledge of small RNA-mediated regulation in grapevine. PMID- 27660498 TI - Mapping Prolificacy QTL in Maize and Teosinte. AB - Teosinte, the ancestor of maize, possesses multiple ears at each node along its main stalk, whereas maize has only a single ear at each node. With its greater ear number, teosinte is referred to as being more prolific. The grassy tillers 1 (gt1) gene has been identified as a large-effect quantitative trait locus underlying this prolificacy difference between maize and teosinte, and the causal polymorphism for the difference was mapped to a 2.7kb control region 5' of the gt1 ORF. The most common maize haplotype (M1) at the gt1 control region confers low prolificacy. A prior study reported that 29% of maize varieties possess the teosinte haplotype (T) for the control region, although these varieties are nonprolific. This observation suggested that these maize lines might possess an additional factor, other than gt1, suppressing prolificacy in maize. We discovered that the factor suppressing prolificacy in maize varieties with the gt1 T haplotype mapped to a 3.20 cM interval, which includes gt1 Subsequent DNA sequence analysis revealed that the maize varieties with the apparent T haplotype actually possess a distinct maize haplotype (M2) that is similar, but not identical, to the T haplotype in sequence but is associated with a nonprolific phenotype similar to the M1 haplotype. Our data indicate that the M2 haplotype or a closely linked factor confers a nonprolific phenotype. Our data suggest that 2 different alleles or haplotypes (M1 and M2) of gt1 were selected during domestication, and that nonprolificacy in all maize varieties is likely a result of allele substitutions at gt1. PMID- 27660499 TI - Bilateral acute closed angle glaucoma associated with the discontinuation of escitalopram: a case report. AB - A 45-year-old woman presented to the Emergency Department complaining of severe headache for 3 hours duration associated with bilateral blurred vision, photophobia, and one attack of vomiting. Her clinical examination revealed normal vital signs and decrease in visual acuity with hazy cornea bilaterally. There were no signs of increased intracranial pressure and no neck rigidity or meningeal signs. The patient was diagnosed with bilateral acute closed angle glaucoma (AACG) with intraocular pressure of 60 mmHg in both eyes. She was using escitalopram for the treatment of depression, which was the only known risk factor for her condition. Standard treatment for AACG was provided. It included topical beta-blocker, alpha agonists, and acetazolamide. This was followed by bilateral peripheral iridotomy. Follow-up intraocular pressure measurement revealed a value of 5 mmHg after 24 hours, indicating complete recovery. To the best of our knowledge, this is the first case to describe AACG after stopping the medication. It is highly important that clinicians be aware of this risk factor for AACG and have high index of suspicion in such patients with vision threatening condition even after discontinuing the medication, because the risk persists for some time. PMID- 27660500 TI - Clinical outcomes of 3-year experience of targeted temperature management in patients with out-of-hospital cardiac arrest at Songklanagarind Hospital in Southern Thailand: an analysis of the MICU-TTM registry. AB - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of intensive care unit admission, which results in high hospital mortality. Targeted temperature management (TTM) was introduced several years ago and is considered to improve neurological and mortality outcomes. This management process was implemented in our hospital in 2012, which was expected to improve the standard of care in OHCA patients. PURPOSE: We aimed to report the clinical and mortality outcomes after TTM was introduced to our hospital in 2012. PATIENTS AND METHODS: An analysis of data from the Medical Intensive Care Unit-TTM registry between 2012 and 2015 was performed. After successful cardiopulmonary resuscitation, TTM was applied to all OHCA patients regardless of causes if there was no contraindication. The Cerebral Performance Category scale score and other clinical outcomes were recorded and analyzed. RESULTS: Out of 23 patients, 87% were male and the mean age was 54.5+/-18.1 years. The causes of OHCA from cardiac etiology comprised 52.2%. The most common initial cardiac rhythm was ventricular fibrillation (47.8%). The survival rate to hospital discharge was 47.8% (11/23), but neurological outcomes were in a persistent vegetative state (8/11, 72.7%). The group with poor neurological outcomes had a significantly higher Acute Physiologic Assessment and Chronic Health Evaluation II score than the group with good neurological outcomes (22.9+/-4.2 vs 16.0+/-3.6, P=0.01). In the multivariate analysis, initial shockable rhythm was associated with survival at hospital discharge (odds ratio 10.1, 95% confidence interval 1.1-94.3, P=0.04). CONCLUSION: TTM in OHCA patients gave better mortality benefits compared to our previous records, despite poor neurological outcomes. Ventilator-associated pneumonia was the major complication of TTM. Therefore, TTM should be considered in OHCA patients, especially in shockable rhythms, after return of spontaneous circulation. PMID- 27660501 TI - Diagnosis and prevention of overtraining syndrome: an opinion on education strategies. AB - Overtraining syndrome is a condition of maladapted physiology in the setting of excessive exercise without adequate rest. The exact etiology and pathogenesis are unknown and being investigated. Symptoms are multisystem in nature and often representative of underlying hormonal, immunologic, neurologic, and psychologic disturbances. Unfortunately, systematic review of the literature does not clearly direct diagnosis, management, or prevention. However, given the severity of symptoms and impairment to quality of life, prevention of overtraining syndrome should be considered by all who interact with endurance athletes. This article will provide suggestions for management of at-risk athletes despite absence of validated diagnostic tests and preventative measures. PMID- 27660502 TI - How do laboratory technicians perceive their role in the tuberculosis diagnostic process? A cross-sectional study among laboratory technicians in health centers of Central Java Province, Indonesia. AB - PURPOSE: Detection of acid-fast bacilli in respiratory specimens serves as an initial pulmonary tuberculosis (TB) diagnosis. Laboratories are the essential and fundamental part of all health systems. This study aimed to describe how laboratory technicians perceived their own self and work. This included perceived self-efficacy, perceived role, perceived equipment availability, perceived procedures, perceived reward and job, and perceived benefit of health education, as well as level of knowledge and attitudes related to work performance of laboratory technicians. METHODS: This was a cross-sectional quantitative study involving 120 laboratory technicians conducted in Central Java. Interviews and observation were conducted to measure performance and work-related variables. RESULTS: Among 120 laboratory technicians, 43.3% showed fairly good performance. They complied with 50%-75% of all procedures, including sputum collection, laboratory tools utilization, sputum smearing, staining, smear examination, grading of results, and universal precaution practice. Perceived role, perceived self-efficacy, and knowledge of laboratory procedures were significantly correlated to performance, besides education and years of working as a laboratory technician. Perceived equipment availability was also significantly correlated to performance after the education variable was controlled. CONCLUSION: Most of the laboratory technicians believed that they have an important role in TB patients' treatment and should display proper self-efficacy in performing laboratory activities. The result may serve as a basic consideration to develop a policy for enhancing motivation of laboratory technicians in order to improve the TB control program. PMID- 27660503 TI - Effectiveness of the behavior change intervention to improve harm reduction self efficacy among people who inject drugs in Thailand. AB - BACKGROUND: People who inject drugs (PWID) in Thailand reported unsafe injection practices resulting in injection-related health consequences. Harm reduction self efficacy plays an important role and could be improved to reduce harm associated with injecting drugs. Evidence-based interventions targeting PWID are needed. This study sought to evaluate the effectiveness of the behavior change intervention within the PWID population. METHODS: The behavior change intervention, Triple-S, was designed to improve harm reduction self-efficacy among PWID. This quasi-experimental study was a pre- and post-comparison with a control group design. Participants were PWID, aged 18-45 years, and located in Bangkok. Changes in harm reduction self-efficacy of the intervention group were compared with the control group using paired and independent t-test. RESULTS: Most of PWID were male (84%), had a secondary school and lower education (71%), were single, and had a mean age of 41 years. They had been injecting drugs for an average of 20 years, and the median of drug injections per week was ten times in the past month. Pre- and post-intervention effects were measured and results showed that the intervention group reported improvement in harm reduction self efficacy in negative emotional conditions (P=0.048). CONCLUSION: Our findings suggest that Triple-S intervention can significantly improve harm reduction self efficacy in negative emotional conditions. The results may suggest the importance of behavior change intervention, especially when integrated with services provided by drop-in centers. The intervention can be further developed to cover other harm reduction behaviors and improve harm reduction self-efficacy. PMID- 27660504 TI - David Kasner, MD, and the Road to Pars Plana Vitrectomy. AB - David Kasner, MD (1927-2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966-1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner's work directly led to further surgical developments, including closed pars plana vitrectomy. PMID- 27660505 TI - Acquired Hemophilia A May Be Associated with Ticagrelor Therapy in a 52-Year-Old Man After a Recent Percutaneous Transluminal Coronary Angioplasty. AB - We present a case report of a 52-year-old man who was hospitalized for right leg pain due to a relevant hemorrhagic effusion. He was on dual antiplatelet therapy (DAPT): acetylsalicylic acid and ticagrelor, a reversible P2Y12 receptor antagonist. Signs, symptoms, and laboratory blood tests led to the diagnosis of acquired hemophilia A (AHA). Ticagrelor therapy-associated AHA was hypothesized due to the fact that, before adding this drug, all laboratory and clinical examinations were repeatedly normal. Prednisone and cyclophosphamide treatment was started without DAPT interruption due to the high risk of stent thrombosis. After 10 days, prolonged activated partial thromboplastin time dropped from 107 to 49 seconds, the patient's factor VIII (FVIII) levels gradually normalized over the following few weeks, and FVIII inhibitor titer was negative. Recently, some reports have established a link between the development of AHA and treatment with clopidogrel, an irreversible P2Y12 receptor antagonist. However, to the best of our knowledge, this is the first time that a link between AHA and ticagrelor has been reported. PMID- 27660506 TI - Monitoring Metastasis and Cachexia in a Patient with Breast Cancer: A Case Study. AB - Cachexia, a wasting syndrome associated with advanced cancer and metastasis, is rarely documented in breast cancer patients. However, the incidence of cachexia in breast cancer is now thought to be largely underestimated. In our case report of a breast cancer patient with bone metastasis monitored during the course of her treatment, we document the development of cachexia by image analysis in relation to her metastatic burden. Elucidation of the link between metastatic burden and cachexia could unveil a highly specific screening process for metastasis, by assessing true muscle mass loss. Our patient was a 49-year-old premenopausal woman, with metastatic invasive ductal breast carcinoma in the vertebral and iliac bones on presentation, which progressed with new metastases to her hips, thigh bones, and vertebrae. In the two-year period, that is between her diagnosis and death, she lost >10% of her baseline weight. During these two years, we retrospectively identified a decrease in paraspinal muscle (PM) at the third lumbar vertebra followed by a sharp decline in weight. The increased tumor burden over time in metastatic sites was accompanied by a decrease in abdominal muscle and visceral and subcutaneous fat and was followed by the patient's demise. The increasing tumor burden in the patient was correlated with the mass of other tissues to determine the tissue that could best serve as a surrogate marker to cachexia and tumor burden. We noted a strong negative correlation between PM area and metastatic tumor area at the third lumbar vertebral level, with PM loss correlating to increasing tumor burden. The monitoring of PM wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and extent of metastatic disease, especially in breast cancer, where metastasis to bone is frequent. Based on our data and review of the literature in this case study, longitudinal monitoring of cachexia in the selected muscle groups can give clinicians early indications of the extent of cachexia in metastatic breast cancer patients. PMID- 27660507 TI - The economic effects of supporting tuberculosis-affected households in Peru. AB - The End TB Strategy mandates that no tuberculosis (TB)-affected households face catastrophic costs due to TB. However, evidence is limited to evaluate socioeconomic support to achieve this change in policy and practice. The objective of the present study was to investigate the economic effects of a TB specific socioeconomic intervention.The setting was 32 shantytown communities in Peru. The participants were from households of consecutive TB patients throughout TB treatment administered by the national TB programme. The intervention consisted of social support through household visits and community meetings, and economic support through cash transfers conditional upon TB screening in household contacts, adhering to TB treatment/chemoprophylaxis and engaging with social support. Data were collected to assess TB-affected household costs. Patient interviews were conducted at treatment initiation and then monthly for 6 months.From February 2014 to June 2015, 312 households were recruited, of which 135 were randomised to receive the intervention. Cash transfer total value averaged US$173 (3.5% of TB-affected households' average annual income) and mitigated 20% of households' TB-related costs. Households randomised to receive the intervention were less likely to incur catastrophic costs (30% (95% CI 22 38%) versus 42% (95% CI 34-51%)). The mitigation impact was higher among poorer households.The TB-specific socioeconomic intervention reduced catastrophic costs and was accessible to poorer households. Socioeconomic support and mitigating catastrophic costs are integral to the End TB strategy, and our findings inform implementation of these new policies. PMID- 27660508 TI - Profiling nitric oxide metabolites in patients with idiopathic pulmonary arterial hypertension. AB - Intact nitric oxide (NO) signalling is critical to maintaining appropriate pulmonary vascular tone. NO bioavailability is reduced in patients with pulmonary arterial hypertension. This study aimed to examine the impact of NO plasma metabolites (NOx) relative to haemodynamic dysfunction and mortality in patients with idiopathic pulmonary arterial hypertension (IPAH).A total of 104 consecutive adult IPAH patients who had undergone genetic counselling when first diagnosed were enrolled in this prospective study.The median concentration of NOx (MUmol.L 1) was significantly lower in IPAH patients compared with healthy subjects, and was decreased further in 19 carriers of the bone morphogenetic protein-receptor type-2 (BMPR2) mutation compared to non-carriers. Reduced concentrations of NOx were correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. Compared with higher baseline NOx concentrations, patients with a NOx concentration of <=10 MUmol.L-1 had a markedly worse survival. After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival. Plasma NOx may be an important biomarker and prognostic indicator, suggesting that reduced NO synthesis contributes to the pathogenesis of IPAH. PMID- 27660509 TI - Surgical lung biopsy for the diagnosis of interstitial lung disease in England: 1997-2008. AB - International guidelines and new targeted therapies for idiopathic pulmonary fibrosis have increased the need for accurate diagnosis of interstitial lung disease (ILD), which may lead to more surgical lung biopsies. This study aimed to assess the risk of this procedure in patients from the UK.We used Hospital Episodes Statistics data from 1997 to 2008 to assess the frequency of surgical lung biopsy for ILD in England, UK. We identified cardiothoracic surgical patients using International Classification of Diseases revision 10 codes for ILD and Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4 codes for surgical lung biopsy. We excluded those with lung resections or lung cancer. We estimated in-hospital, 30-day and 90-day mortality following the procedure, and linked to cause of death using data from the UK Office of National Statistics.We identified 2820 patients with ILD undergoing surgical lung biopsy during the 12-year period. The number of biopsies increased over the time period studied. In-hospital, 30-day and 90-day mortality were 1.7%, 2.4% and 3.9%, respectively. Male sex, increasing age, increasing comorbidity and open surgery were risk factors for mortality.Surgical lung biopsy for ILD has a similar mortality to lobectomy for lung cancer, and clinicians and patients should understand the likely risks involved. PMID- 27660510 TI - Acromegaly in sleep apnoea patients: a large observational study of 755 patients. PMID- 27660511 TI - Bosutinib therapy resulting in severe deterioration of pre-existing pulmonary arterial hypertension. PMID- 27660512 TI - Exercise cardiac MRI-derived right ventriculo-arterial coupling ratio detects early right ventricular maladaptation in PAH. PMID- 27660513 TI - Survival of Mycobacterium abscessus isolated from people with cystic fibrosis in artificially generated aerosols. PMID- 27660514 TI - Lower lung function associates with cessation of menstruation: UK Biobank data. AB - Little is known about the effect of cessation of menstruation on lung function. The aims of the study were to examine the association of lung function with natural and surgical cessation of menstruation, and assess whether lower lung function is associated with earlier age at cessation of menstruation.The study was performed in 141 076 women from the UK Biobank, who had provided acceptable and reproducible spirometry measurements and information on menstrual status. The associations of lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), spirometric restriction (FVC < lower limit of normal (LLN)), airflow obstruction (FEV1/FVC =10 pack-years. Spirometry evaluation points were: 1) baseline, 2) the maximum lung function during the first 2.5 years after diagnosis (Max0-2.5) and 3) after 12 years of follow-up.Between Max0-2.5 and follow-up, the median annual decline in absolute forced expiratory volume in 1 s (FEV1) was 36 mL in the group of patients with <10 pack-years of smoking and 54 mL in those with smoking history >=10 pack-years (p=0.003). The annual declines in FEV1 % pred (p=0.006), forced vital capacity (FVC) (p=0.035) and FEV1/FVC (p=0.045) were also accelerated in the group of patients with >=10 pack-years smoked. In multivariate regression analysis, smoking history >=10 pack-years became a significant predictor of accelerated decline in FEV1Among patients with clinically defined adult-onset asthma, smoking history >=10 pack-years is associated with accelerated loss of lung function. PMID- 27660516 TI - Sarcoidosis-related mortality in France: a multiple-cause-of-death analysis. AB - We evaluated mortality rates and underlying causes of death among French decedents with sarcoidosis from 2002 to 2011.We used data from the French Epidemiological Centre for the Medical Causes of Death to 1) calculate sarcoidosis-related mortality rates, 2) examine differences by age and gender, 3) determine underlying and nonunderlying causes of death, 4) compare with the general population (observed/expected ratios), and 5) analyse regional differences.1662 death certificates mentioning sarcoidosis were recorded. The age standardised mortality rate was 3.6 per million population and significantly increased over the study period. The mean age at death was 70.4 years (versus 76.2 years for the general population). The most common underlying cause of death was sarcoidosis. Sarcoidosis decedents were more likely to be males when aged <65 years. When sarcoidosis was the underlying cause of death, the main other mentions on death certificates were chronic respiratory and cardiovascular diseases. The overall observed/expected ratio was >1 for infectious disease, tuberculosis and chronic respiratory disease, and <1 for neoplasms. We observed a north-south gradient of age-standardised mortality ratio at the country level.Despite the limitation of possibly capturing the more severe cases of sarcoidosis, this study may help define and prioritise preventive interventions. PMID- 27660517 TI - Outcome during and after anticoagulant therapy in cancer patients with incidentally found pulmonary embolism. AB - Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism.We used the Registro Informatizado de Enfermedad TromboEmbolica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism.As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient years, respectively); however, there were no differences in the rate of fatal events at one death each.The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies. PMID- 27660519 TI - The Mechanisms of the Regulation of Immune Response in Patients with Comorbidity of Chronic Obstructive Pulmonary Disease and Asthma. AB - Background. Comorbidity of chronic obstructive pulmonary disease (COPD) and asthma (asthma COPD overlap syndrome, ACOS) is a significant problem in pulmonary practice, whose pathogenetic issues are not clarified yet. Objective. To study the features of the regulation of immune response in patients with comorbid COPD and asthma. Methods. We assessed the levels of CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, HLA-DR, total IgE, TNF-alpha, IL-4, IFN-gamma, TXB2, and LTB4 in patients with comorbid COPD and asthma. Results. The study involved 44 people with COPD, 39 people with asthma, and 12 people with comorbid COPD and asthma. The specific features in comorbid COPD and asthma were lymphocytosis, increased absolute count of T-helper cells, increased cytotoxic T-lymphocytes in relative and absolute count, increased relative and absolute numbers of B-lymphocytes, and high levels of total IgE. The elevated levels of TNF-alpha and IL-4 and inhibition of IFN-gamma production were detected. The content of LTB4 was maximal; TXB2 levels were higher than in control group but lower than in COPD and asthma. Conclusion. In comorbid COPD and asthma inflammation increased even during stable period. High levels of eicosanoids, low production of Th1-type cytokines, and active synthesis of opposition IL-4, along with increased IgE, indicate the activation of Th2-type immune response. PMID- 27660520 TI - A new spider species, Heser stoevi sp. nov., from Turkmenistan (Araneae: Gnaphosidae). AB - BACKGROUND: The genus Heser (Araneae, Gnaphosidae) belongs to the Zelotes group, and is currently known to comprise 10 species distributed in Africa, Asia, Europe and North America. The type species is Heser malefactor Tuneva, 2004 from Kazakhstan. NEW INFORMATION: A new spider species, Heser stoevi sp. nov. (male and female) found in Koytendag Mountains, southeastern Turkmenistan is described and illustrated. It is morphologically close to H. aradensis (Levy, 1998) from Israel but can be readily distinguished by the longer embolus, the smaller and flattened conductor, the lack of retrolateral tibial apophysis, all this coupled with very distinctive female copulatory organs. The new species was found under stones in arid grassland habitats. PMID- 27660518 TI - Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells. AB - Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages. PMID- 27660521 TI - AxIOM: Amphipod crustaceans from insular Posidonia oceanica seagrass meadows. AB - BACKGROUND: The Neptune grass, Posidonia oceanica (L.) Delile, 1813, is the most widespread seagrass of the Mediterranean Sea. This foundation species forms large meadows that, through habitat and trophic services, act as biodiversity hotspots. In Neptune grass meadows, amphipod crustaceans are one of the dominant groups of vagile invertebrates, forming an abundant and diverse taxocenosis. They are key ecological components of the complex, pivotal, yet critically endangered Neptune grass ecosystems. Nevertheless, comprehensive qualitative and quantitative data about amphipod fauna found in Mediterranean Neptune grass meadows remain scarce, especially in insular locations. NEW INFORMATION: Here, we provide in-depth metadata about AxIOM, a sample-based dataset published on the GBIF portal. AxIOM is based on an extensive and spatially hierarchized sampling design with multiple years, seasons, day periods, and methods. Samples were taken along the coasts of Calvi Bay (Corsica, France) and of the Tavolara-Punta Coda Cavallo Marine Protected Area (Sardinia, Italy). In total, AxIOM contains 187 samples documenting occurrence (1775 records) and abundance (10720 specimens) of amphipod crustaceans belonging to 72 species spanning 29 families. The dataset is available at http://ipt.biodiversity.be/resource?r=axiom. PMID- 27660522 TI - Species conservation profile of the cave spider Turinyphia cavernicola (Araneae, Linyphiidae) from Terceira Island, Azores, Portugal. PMID- 27660524 TI - Species Conservation Profiles compliant with the IUCN Red List of Threatened Species. PMID- 27660523 TI - The Global Registry of Biodiversity Repositories: A Call for Community Curation. AB - The Global Registry of Biodiversity Repositories is an online metadata resource for biodiversity collections, the institutions that contain them, and associated staff members. The registry provides contact and address information, characteristics of the institutions and collections using controlled vocabularies and free-text descripitons, links to related websites, unique identifiers for each institution and collection record, text fields for loan and use policies, and a variety of other descriptors. Each institution record includes an institutionCode that must be unique, and each collection record must have a collectionCode that is unique within that institution. The registry is populated with records imported from the largest similar registries and more can be harmonized and added. Doing so will require community input and curation and would produce a truly comprehensive and unifying information resource. PMID- 27660525 TI - Checklist of the family Epitoniidae (Mollusca: Gastropoda) in Taiwan with description of a new species and some new records. AB - BACKGROUND: The family Epitoniidae is a group of small to medium-sized gastropods and occurs globally from the intertidal zone to abyssal seabeds. There are 101 epitoniid species currently recorded from Taiwan. NEW INFORMATION: Based on our investigations of seashores and fishing ports of Taiwan, a new species and 12 new records of Epitoniidae species are reported. Of the 12 new records, four are new to the East Asian region and two are new records to the Indo-Pacific region. Our results increase the number of Taiwanese Epitoniidae from 101 species to 114 species. PMID- 27660526 TI - An occurence records database of Irregular Echinoids (Echinodermata: Echinoidea) in Mexico. AB - BACKGROUND: Research on echinoderms in Mexico began in the late nineteenth century. We present a dataset that includes the taxonomic and geographic information of irregular echinoids from Mexico, housed in four collections: 1) Coleccion Nacional de Equinodermos "Ma. Elena Caso Munoz" from the Instituto de Ciencias del Mar y Limnologia (ICML), Universidad Nacional Autonoma de Mexico (UNAM); 2) Invertebrate Zoology Collection, Smithsonian Museum of Natural History, Washington, D.C., United States of America (USA); 3) Invertebrate Collection, Museum of Comparative Zoology, University of Harvard, Boston, Massachusetts, USA and 4) Invertebrate Zoology, Peabody Museum, Yale University, New Haven, Connecticut, USA. NEW INFORMATION: A total of six orders, 17 families, 35 genera and 68 species are reported, 37 distributed in the Pacific coast and 31 in the Atlantic coast, none of them was found in both coasts. The most diverse region is the Gulf of California (S=32); the most diverse order is Spatangoida with 31 species reported in mexican waters. PMID- 27660527 TI - The cicadas (Hemiptera: Cicadidae) of India, Bangladesh, Bhutan, Myanmar, Nepal and Sri Lanka: an annotated provisional catalogue, regional checklist and bibliography. AB - BACKGROUND: The cicadas of the Indian subcontinent, like many other insects in the region, have remained understudied since the early part of the 20th Century, and await modern taxonomic, systematic and phylogenetic treatment. This paper presents an updated systematic catalogue of cicadas (Hemiptera: Cicadidae) from India, Bangladesh, Bhutan, Myanmar, Nepal and Sri Lanka, the first in over a century. NEW INFORMATION: This paper treats 281 species, including: India and Bangladesh (189 species), Bhutan (19 species), Myanmar (81 species), Nepal (46 species) and Sri Lanka (22 species). For each species all recognized junior synonyms are included with information on the type material and additional specimens where relevant. The global distributional range and notes on the taxonomy of each species are included where appropriate. Two lists are provided: (1) species known to occur in India and Bangladesh (treated as a geographic unit), Bhutan, Myanmar, Nepal and Sri Lanka; and (2) species previously listed from these countries in error. A bibliography of species descriptions is provided, with the papers containing the original descriptions provided where copyright allows. PMID- 27660528 TI - Aquatic Insects from the Caatinga: checklists and diversity assessments of Ubajara (Ceara State) and Sete Cidades (Piaui State) National Parks, Northeastern Brazil. AB - BACKGROUND: Diversity and distribution of Neotropical aquatic insects is still poorly known, with many species to be recorded and many others to be described, due to the small number of taxonomists and sparse faunistic studies. This knowledge is especially poor in the Caatinga Domain in Northeastern Brazil, even though, this region may have played an important historical role in the spatial evolution of faunas of forested areas in northern South America. NEW INFORMATION: Aquatic insect checklists of 96 species from Parque Nacional de Ubajara (Ceara State, Brazil) and 112 species from Parque Nacional de Sete Cidades (Piaui State, Brazil) are presented, representing the following taxa: Elmidae, Epimetopidae, Hydrophilidae, and Torridincolidae (Coleoptera), Hemerodromiinae (Diptera: Empididae), Ephemeroptera, Gerromorpha and Nepomorpha (Hemiptera), Odonata, Plecoptera, and Trichoptera. Because of the scarce number of biological inventories in Northeastern Brazil, several new distributional records (of species, genera, and families) for Brazil, Northeastern Brazil, and Ceara and Piaui states are provided. In addition, several undescribed species were detected, being 26 from Ubajara and 20 from Sete Cidades. Results represent a significant increase to the known fauna of these states, ranging from 13%-70% increase for Ceara and 41% to 91% increase for Piaui. Although both parks are relatively close to each other and within the Caatinga domain, their aquatic fauna display a very high complementarity (89% species), possibly due to structural differences of water bodies sampled in each park. Rarefaction curves based on quantitative light trap samples suggest a much higher expected species richness of aquatic insects at Sete Cidades than at Ubajara National Park. Discussion on biogeographical affinities of this sample of the Caatinga fauna is provided. PMID- 27660530 TI - Five Years Later: An Update on the Status of Collections of Endemic Gulf of Mexico Fishes Put at Risk by the 2010 Oil Spill. AB - BACKGROUND: The 2010 Gulf of Mexico Oil Spill took place over 180,000 square kilometers during a 12-week period over five years ago; however, this event continues to influence the development and distribution of organisms in and around the region of the disaster. Here we examine fish species that may have been most affected by noting their past distribution in the region of the spill and examining data of known collecting events over the last 10 years (five years prior to the spill, five years post spill). NEW INFORMATION: We found that more than half of the endemic fish species of the Gulf (45 of 77). PMID- 27660529 TI - Species composition, community and population dynamics of two gallery forests from the Brazilian Cerrado domain. AB - BACKGROUND: To understand the impacts of global changes on future community compositions, knowledge of community dynamics is of crucial importance. To improve our knowledge of community composition, biomass stock and maintenance of gallery forests in the Brazilian Cerrado, we provide two datasets from the 0.5 ha Corrego Fazendinha Gallery Forest Dynamics Plot and the Corrego Fundo Gallery Forest Dynamics Plot situated in the Bom Despacho region, Minas Gerais, Southeastern Brazil. NEW INFORMATION: We report diameter at breast height, basal area and height measurements of 3417 trees and treelets identified during three censuses in both areas. PMID- 27660531 TI - Fauna Europaea - Orthopteroid orders. AB - Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all extant European terrestrial and freshwater animals, their geographical distribution at the level of countries and major islands (west of the Urals and excluding the Caucasus region), and some additional information. The Fauna Europaea project comprises about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies, which is much more than the originally projected number of 100,000 species. Fauna Europaea represents a huge effort by more than 400 contributing specialists throughout Europe and is a unique (standard) reference suitable for many users in science, government, industry, nature conservation and education. The "Orthopteroid orders" is one of the 58 Fauna Europaea major taxonomic groups. It contains series of mostly well-known insect orders: Embiodea (webspinners), Dermaptera (earwigs), Phasmatodea (walking sticks), Orthoptera s.s. (grasshoppers, crickets, bush-crickets) and Dictyoptera with the suborders Mantodea (mantids), Blattaria (cockroaches) and Isoptera (termites). For the Orthopteroid orders, data from 35 families containing 1,371 species are included in this paper. PMID- 27660532 TI - First report of Cheiloneurus exitiosus (Perkins, 1906) and Helegonatopus dimorphus (Hoffer, 1954) (Hymenoptera: Encyrtidae) from Japan, with remarks on their abundance in rice paddies. AB - BACKGROUND: Encyrtid secondary parasitoids of Delphacidae have not been recorded in Japan. However, they may play an important role in the rice ecosystem because they can reduce the number of Dryinidae, the natural enemies of rice planthoppers. NEW INFORMATION: We found two encyrtid species, Cheiloneurus exitiosus (Perkins, 1906) and Helegonatopus dimorphus (Hoffer, 1954), from rice paddies and the surrounding environment. Haplogonatopus oratorius (Westwood, 1833) and Anteon sp. were newly recognized as hosts of He. dimorphus. Parasitism of C. exitiosus was rare, but He. dimorphus was common in Kumamoto Prefecture. The sex ratio (male proportion) and clutch size of He. dimorphus was estimated as 0.19 and 4.95, respectively. PMID- 27660533 TI - Abyssal fauna of the UK-1 polymetallic nodule exploration area, Clarion Clipperton Zone, central Pacific Ocean: Cnidaria. AB - BACKGROUND: We present data from a DNA taxonomy register of the abyssal Cnidaria collected as part of the Abyssal Baseline (ABYSSLINE) environmental survey cruise 'AB01' to the UK Seabed Resources Ltd (UKSRL) polymetallic-nodule exploration area 'UK-1' in the eastern Clarion-Clipperton Zone (CCZ), central Pacific Ocean abyssal plain. This is the second paper in a series to provide regional taxonomic data for a region that is undergoing intense deep-sea mineral exploration for high-grade polymetallic nodules. Data were collected from the UK-1 exploration area following the methods described in Glover et al. (2015b). NEW INFORMATION: Morphological and genetic data are presented for 10 species and 18 records identified by a combination of morphological and genetic data, including molecular phylogenetic analyses. These included 2 primnoid octocorals, 2 isidid octocorals, 1 anemone, 4 hydroids (including 2 pelagic siphonophores accidentally caught) and a scyphozoan jellyfish (in the benthic stage of the life cycle). Two taxa matched previously published genetic sequences (pelagic siphonophores), two taxa matched published morphological descriptions (abyssal primnoids described from the same locality in 2015) and the remaining 6 taxa are potentially new species, for which we make the raw data, imagery and vouchers available for future taxonomic study. We have used a precautionary approach in taxon assignments to avoid over-estimating species ranges. The Clarion-Clipperton Zone is a region undergoing intense exploration for potential deep-sea mineral extraction. We present these data to facilitate future taxonomic and environmental impact study by making both data and voucher materials available through curated and accessible biological collections. For some of the specimens we also provide image data collected at the seabed by ROV, wich may facilitate more accurate taxon designation in coming ROV or AUV surveys. PMID- 27660534 TI - First Canadian record of the water mite Thermacarus nevadensis Marshall, 1928 (Arachnida: Acariformes: Hydrachnidiae: Thermacaridae) from hot springs in British Columbia. AB - BACKGROUND: Thermacarus nevadensis Marshall, 1928 is an uncommonly collected mite associated with hot spring environments in the western United States. Information on its distribution and ecology are incomplete. NEW INFORMATION: In this paper, we report Thermacarus nevadensis from northern British Columbia. These records represent the first of Thermacaridae from Canada, the most northern records of this species in North America, and the most northern records for the family globally. We also provide short notes and images of the habitats in which specimens have been collected in Canada. PMID- 27660535 TI - Records of Wenchengia (Lamiaceae) from Vietnam. AB - BACKGROUND: The monotypic genus Wenchengia (Lamiaceae) has been thought to be endemic to Hainan, China. This paper reports on historic records of Wenchengia alternifolia collected from Vietnam. The recent recuration and modernisation of the Paris herbarium greatly facilitated this discovery. NEW INFORMATION: During preparatory work supporting the account for the Lamiaceae of the Flora of Thailand, three specimens of Wenchengia from central Vietnam were found in the Herbarium of the Musuem National d'Histoire Naturelle in Paris (P), and subsequently two duplicates were found in the Herbarium at Kew (K, abbreviations following Thiers 2016). The specimens were collected in and before 1927 and it is not known if the species is still extant in Vietnam. Searches for extant populations should focus in the Ba Na Hills or Bach Ma National Park, central Vietnam. PMID- 27660536 TI - Terrestrial arthropods of Steel Creek, Buffalo National River, Arkansas. IV. Asilidae and other Diptera. AB - BACKGROUND: This is the fourth in a series of papers detailing the terrestrial arthropods collected during an intensive survey of a site near Steel Creek campground along the Buffalo National River in Arkansas. The survey was conducted over a period of eight and a half months in 2013 using twelve trap types, including Malaise and canopy traps, Lindgren multifunnel traps, and pan traps. NEW INFORMATION: We provide collection records for 38 species of Asilidae and other Diptera, 7 of which are new state records for Arkansas: (Asilidae) Lasiopogon opaculus Loew, 1874; (Lygistorrhinidae) Lygistorrhina sancthecatharinae Thompson, 1975; (Stratiomyidae) Cephalochrysa nigricornis (Loew, 1866), Gowdeyana punctifera (Malloch, 1915), Sargus decorus Say, 1824; (Ulidiidae) Callopistromyia annulipes Macquart, 1855; and (Xylophagidae) Rachicerus obscuripennis Loew, 1863. PMID- 27660537 TI - Small-Maturity Asymptotics for the At-The-Money Implied Volatility Slope in Levy Models. AB - We consider the at-the-money (ATM) strike derivative of implied volatility as the maturity tends to zero. Our main results quantify the behaviour of the slope for infinite activity exponential Levy models including a Brownian component. As auxiliary results, we obtain asymptotic expansions of short maturity ATM digital call options, using Mellin transform asymptotics. Finally, we discuss when the ATM slope is consistent with the steepness of the smile wings, as given by Lee's moment formula. PMID- 27660539 TI - Malaysian Journal of Medical Sciences' Publishing Report (2014-2015). AB - The Malaysian Journal of Medical Sciences (MJMS) has conducted a simple analysis of its scholarly publication, based on the auto-generated data compiled from ScholarOne Manuscripts(TM), an innovative, web-based, submission and peer-review workflow solution for scholarly publishers. The performance of the MJMS from 2014 2015 is reported on in this editorial, with a focus on the pattern of manuscript submission, geographical contributors and the acceptance-rejection rate. The total number of manuscript submissions has increased from 264 in 2014, to 272 in 2015. Malaysians are the main contributors to the MJMS. The total number of manuscript rejections following the review process was 79 (29.9%) in 2014, increasing to 92 (33.8%) the following year, in accordance with the exacting quality control criteria applied by the journal's editor to the submitted manuscripts. PMID- 27660540 TI - Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram. AB - Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/depression (LTP /LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses. PMID- 27660541 TI - Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis (MDR- TB) Compared with Non-MDR-TB Infections in Peninsular Malaysia. AB - BACKGROUND: Treating patients with multidrug-resistant tuberculosis (MDR-TB) strains is more complicated, complex, toxic, expensive, than treating patients with susceptible TB strains. This study aims to compare the treatment outcomes and potential factors associated between patients with MDR-TB and non MDR TB infections in peninsular Malaysia. METHODS: This study was a retrospective cohort study. Data were collected from the medical records of all registered MDR-TB patients and Non-MDR-TB patients at five TB hospitals in peninsular Malaysia from January 2010 to January 2014. RESULTS: A total of 314 subjects were studied, including 105 MDR-TB cases and 209 non-MDR-TB. After TB treatment, 24.8% of the MDR-TB patients and 17.7% of non MDR TB relapsed; 17.1% of the MDR-TB patients and 16.3% of non MDR TB defaulted from TB treatment. A significant difference seen in treatment success rate 17.1% for MDR-TB; 63.1% for non MDR TB (P < 0.001)). Mortality rate were 8.9% for MDR-TB; 13.2% for non MDR TB. Multivariable analysis showed the potential factors associated with poor treatment outcomes were presence of HIV infection (AOR, 1.09; 95%CI: 1.05, 1.75; P = 0.001) and previous TB treatment (AOR, 4.87; 95%CI: 2.84, 8.38; P = 0.001). CONCLUSION: This study revealed that the treatment success rate in patients with non MDR TB infection was higher than MDR-TB. Unsuccessful treatment was seen in MDR-TB associated with potential factors such as history of TB treatment, and presence of HIV infection. PMID- 27660542 TI - The Combination of Sonography and Physical Examination Improves the Patency and Suitability of Hemodialysis Arteriovenous Fistula in Vascular Access. AB - PURPOSE: We compared the patency and the suitability of arteriovenous fistula (AVF) created for vascular access by two approaches: (a) physical examination with preoperative vascular mapping and (b) physical examination alone. METHODS: We compared the patency and the suitability of AVF created in patients for dialysis. There were two cohorts of patients of 79 patients each: (a) patients with AVF created based on the combination of physical examination and preoperative vascular mapping (PE+VM) and (b) patients with AVF created based on physical examination (PE) alone. Fistula patency is defined as clinical detection of thrill (or auscultation) of murmur over the fistula and coded as having thrills (patent) versus not having thrills (not patent). Suitability of fistula is defined as functioning AVF (AVF can be adequately used via 2-needle cannulation for dialysis) and coded as suitable versus not suitable. RESULTS: AVF created after the preoperative vascular mapping (PE+VM) has 5.70 (at six weeks) and 3.76 (at three months) times higher chance for patency, and 3.08 times higher chance for suitable AVF for dialysis than AVF created after the physical examination (PE) alone. CONCLUSION: Physical examination with preoperative ultrasound mapping (PE+VM) significantly improves the short term patency and the suitability of AVF for dialysis. PMID- 27660543 TI - Psychometric Properties of the Heart Disease Knowledge Scale: Evidence from Item and Confirmatory Factor Analyses. AB - BACKGROUND: Heart disease knowledge is an important concept for health education, yet there is lack of evidence on proper validated instruments used to measure levels of heart disease knowledge in the Malaysian context. METHODS: A cross sectional, survey design was conducted to examine the psychometric properties of the adapted English version of the Heart Disease Knowledge Questionnaire (HDKQ). Using proportionate cluster sampling, 788 undergraduate students at Universiti Sains Malaysia, Malaysia, were recruited and completed the HDKQ. Item analysis and confirmatory factor analysis (CFA) were used for the psychometric evaluation. Construct validity of the measurement model was included. RESULTS: Most of the students were Malay (48%), female (71%), and from the field of science (51%). An acceptable range was obtained with respect to both the difficulty and discrimination indices in the item analysis results. The difficulty index ranged from 0.12-0.91 and a discrimination index of >= 0.20 were reported for the final retained 23 items. The final CFA model showed an adequate fit to the data, yielding a 23-item, one-factor model [weighted least squares mean and variance adjusted scaled chi-square difference = 1.22, degrees of freedom = 2, P-value = 0.544, the root mean square error of approximation = 0.03 (90% confidence interval = 0.03, 0.04); close-fit P-value = > 0.950]. CONCLUSION: Adequate psychometric values were obtained for Malaysian undergraduate university students using the 23-item, one-factor model of the adapted HDKQ. PMID- 27660544 TI - Validation of Perceived Wellness Survey (PWS) in a Sample of Iranian Population. AB - The individual's perception of health, when health is understood to include many dimensions of life, is considered the basis for any improvement in health status. Therefore, the present study aimed to assess the reliability and validity of the Persian version of the Perceived Wellness Scale (PWS) by applying it to employees of the Shiraz University of Medical Sciences. This cross-sectional study was conducted with 180 staff members of the university selected by convenience sampling. The study instrument was a Persian version of the PWS prepared through a translation and back-translation process. The reliability and validity of the instrument were assessed by using confirmatory factor analysis (CFA) and Cronbach's alpha coefficient. A total of 180 employees participated in the study. The mean age of the participants was 32.29 years (SD = 7.39) and 78.1% of the participants were women. The results showed that the Persian version of the PWS is acceptable. Cronbach's alpha coefficient was 0.87 for the whole scale, ranging from 0.68 to 0.85 on different dimensions of the scale. The results of split-half reliability and CFA indicated that the reliability and validity of the PWS are acceptable. The PWS is therefore an effective tool for evaluating the different dimensions of perceived wellness in the Iranian population. PMID- 27660545 TI - Office Exercise Training to Reduce and Prevent the Occurrence of Musculoskeletal Disorders among Office Workers: A Hypothesis. AB - Pain in specific areas of the body (including the lower back, neck, and shoulders) due to extended periods of sitting and inactivity is the most widespread musculoskeletal disorder worldwide and has consequences that are both socio-economic and personal. This condition is particularly prevalent in industrialised countries, affecting roughly 70% to 80% of adults at some point in their lives; approximately 1% of the U.S. population is chronically disabled by this type of pain disorder. A practical way to reduce the prevalence of musculoskeletal pain among office workers would have a significant positive impact. More work is required to develop a package of exercises designed to prevent and treat musculoskeletal pain in office workers. Such a package would be preferable to pharmacological treatments, which can have undesirable side effects. The main objective of this package would be to increase the flexibility and strength of trunk muscles in order to decrease the soreness, pain, and degree of discomfort. In this article, we introduce our proposed package of exercises, which are based on guidelines issued bythe American College of Sports Medicine. PMID- 27660546 TI - Onyx in Brain Arteriovenous Malformation Embolisation. AB - INTRODUCTION: Embolisation has long been used as an adjunct to surgical resection in the treatment of brain arteriovenous malformation (bAVM). The most commonly used embolic material, n-butylcyanoacrylate glue, requires experience and skill to handle its quick and unpredictable flow and polymerisation. A new liquid embolic agent, ethylene vinyl alcohol copolymer (Onyx), is less adhesive and polymerises slowly, which provides better control for radiologists performing embolisation. OBJECTIVE: To report our experience in embolisation using Onyx alone or in combination with histoacryl for bAVM embolisation in our tertiary referral centre. METHODS: We retrospectively reviewed the anatomy, technical conditions, complications and clinical outcome of all bAVM patients embolised at our centre using Onyx alone or in combination with n-butylcyanoacrylate glue. RESULTS: Between 2010 and 2013, 13 patients [6 (46.2%) male; 7 (53.8%) female; aged, 14-57 years] were included, and a total of 31 embolisations were performed. Clinical presentation included hemorrhage [9 (69.2%)], seizures [2 (15.4%)], and headache [2 (15.4%)]. Most AVMs were located in the brain hemispheres [12 (92.3%)] and measured <3 cm [7 (53.8%]. Complete occlusion of the AVM was obtained in 2 (15.4%) patients; 11 (84.6%) patients had partial occlusion [6 (54.5%) had <50% nidus occlusion]. Complications occurred in four procedures involving 3 patients (morbidity, 23.1%). This resulted in the death of 1 patient (mortality, 7.7%) and complete recovery with no disability in 2 patients. CONCLUSION: The total nidal occlusion achieved herein is comparable to other similar studies. Our morbidity and mortality were higher compared to other studies which may be attributed to the small number of patients. More data is being collected which may better reflect on our experience. PMID- 27660547 TI - A Ten-Year Kuala Lumpur Review on Laser Posterior Cordectomy for Bilateral Vocal Fold Immobility. AB - Bilateral vocal fold immobility (BVFI) is commonly caused by injury to the recurrent laryngeal nerve (RLN) and leads to stridor and dyspnea of varying onsets. A retrospective study was done at the Department of Otorhinolaryngology of Universiti Kebangsaan Malaysia Medical Centre on laser microsurgical posterior cordectomy for BVFI. The objectives were to identify the average duration of onset of stridor from the time of insult and to evaluate the outcome of laser posterior cordectomy as a surgical option. From 1997 to 2007, a total of 31 patients with BVFI were referred for surgery. Twelve patients had tracheostomy done prior to the procedure, whereas 19 patients were without tracheostomy. Ten patients were successfully decannulated, and only 4 patients had complications related to the procedure. The minimum onset of stridor was 7 months, maximum onset of stridor was 28 years, and the mean onset of stridor was 8.7 years. The commonest complication observed was posterior glottic adhesion following bilateral posterior cordectomy. Laser endolaryngeal posterior cordectomy is an excellent surgical option as it enables successful decannulation or avoidance of tracheostomy in patients with BVFI. The onset of stridor took years after the insult to the recurrent laryngeal nerves. PMID- 27660549 TI - Rare Presentation of Pseudomyxoma Retroperitonei: Stretching the Limits. AB - A 55-year-old woman presented with a mucopurulent sinusal discharge from the right supragluteal region, with symptoms over the previous five months. This abscess began as a slowly swelling growth, which eventually turned into a discharging sinus, and she was diagnosed with a gluteal abscess. The patient underwent incisional drainage, and intra-operatively, the sinus tract could be seen extending to the retroperitoneum. A subsequent CT scan and an MRI of the abdomen revealed a large heterogeneous retroperitoneal cystic mass on the right side of midline, extending inferiorly into the anterior thigh along the iliopsoas. Superiorly, a tubular projection extended from the lesion, indenting the ileocaecal junction, while a fluid filled cutaneous fistulous tract was seen, extending to the right flank. A diagnosis of pseudomyxoma retroperitonei, likely of retrocaecal appendicular origin, was proposed. An explorative laparotomy with an appendectomy, and the evacuation of the retroperitoneal collection were completed. The subsequent histopathology confirmed the diagnosis of appendicular mucinous cystadenoma, with pseudomyxoma retroperitonei. PMID- 27660548 TI - Thymectomy for Myasthenia Gravis: A 10-year Review of Cases at the Hospital Universiti Sains Malaysia. AB - BACKGROUND: A thymectomy is considered effective for patients with myasthenia gravis (MG). Although a few studies have described the role of a thymectomy in the treatment of MG in Asians countries, there are no published data on the application of this surgical approach for MG in Malaysia. We aimed to describe the clinical outcomes of MG patients who underwent a thymectomy and the factors affecting these outcomes. METHODS: This was a retrospective study involving 16 patients with MG who underwent a thymectomy at the Hospital Universiti Sains Malaysia (HUSM) from January 2002 until December 2012, with a follow-up period ranging from 3-120 months. RESULTS: The study consisted of 16 patients aged 22-78 years, 10 of whom were males. The overall remission/improvement rate was 87.5%, and the rate of clinical outcomes classified as unchanged/worsened was 12.5%. Thymomamatous or non-thymomamatous MG, histology features, Osserman stage and the duration of follow-up were not significant prognostic factors. Post-operative mortality was 6.2% (1 of 16 patients died of septic shock). CONCLUSION: A thymectomy seems to be an effective treatment for MG, with low surgical morbidity. Patients with a lower Osserman stage and those with/without thymomas had favourable outcomes. PMID- 27660551 TI - To Err is Human, But Failing to Attempt is Negligence: The Hidden Perspectives That Limit Intravenous Antibiotic Administration During Third Molar Surgery in General Practice. PMID- 27660550 TI - Unicentric Castleman Disease: An Unusual Cause of An Isolated Neck Mass. AB - Castleman disease (CD) is a rare lymphoproliferative disorder of unknown aetiology. It manifests in two distinct clinical presentations: unicentric and multicentric. Unicentric CD is rare and may present as an isolated neck mass. A 22-year-old man presented with a 6-month history of right neck swelling that occupied the posterior triangle of the right neck region. After surgical exploration, a solitary, well defined, and hyper vascular mass was excise. A histopathological examination confirmed the lesion as CD, hyaline-vascular variant. CD of the neck is a diagnosis that is usually not taken into consideration while evaluating neck masses due to its rarity and unassuming presentation. It should be keep in the differential diagnosis of neck masses as the clinical and radiological features evade a firm diagnosis. The treatment of unicentric CD is complete surgical excision, which cures the patient. PMID- 27660552 TI - Synthesis, isolation and purification of [(11)C]-choline. AB - [(11)C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [(11)C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [(11)C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [(11)C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [(11)C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [(11)C]-target containing cyclotron. PMID- 27660553 TI - Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders. AB - This is the protocol for a review and there is no abstract. The objectives are as follows: To compare a therapeutic-only versus prophylactic platelet transfusion policy for people with myelodysplasia, inherited or acquired aplastic anaemia, and other congenital bone marrow failure disorders. PMID- 27660554 TI - Motivational interviewing competencies among UK family nurse partnership nurses: a process evaluation component of the building blocks trial. AB - BACKGROUND: Motivational Interviewing (MI) is a person-centred counselling approach to behaviour change which is increasingly being used in public health settings, either as a stand-alone approach or in combination with other structured programmes of health promotion. One example of this is the Family Nurse Partnership (FNP) a licensed, preventative programme for first time mothers under the age of 20, delivered by specialist family nurses who are additionally trained in MI. The Building Blocks trial was an individually randomised controlled trial comparing effectiveness of Family Nurse Partnership when added to usual care compared to usual care alone within 18 sites in England. The aim of this process evaluation component of the trial is to determine the extent to which Motivational Interviewing skills taught to Family Nurse Partnership nurses were used in their home visits with clients. METHODS: Between July 2010 and November 2011, 92 audio-recordings of nurse-client consultations were collected during the 'pregnancy' and 'infancy' phases of the FNP programme. They were analysed using The Motivational Interviewing Treatment Integrity (MITI) coding system. RESULTS: A competent level of overall MI adherent practice according to the MITI criteria for 'global clinician ratings' was apparent in over 70 % of the consultations. However, on specific behaviours and the MITI-derived practitioner competency variables, there was a large variation in the percentage of recordings in which "beginner proficiency" levels in MI (as defined by the MITI criteria) was achieved, ranging from 73.9 % for the 'MI adherent behaviour' variable in the pregnancy phase to 6.7 % for 'percentage of questions coded as open' in the infancy phase. CONCLUSIONS: The results suggest that it is possible to deliver a structured programme in an MI-consistent way. However, some of the behaviours regarded as key to MI practice such as the percentage of questions coded as open can be more difficult to achieve in such a context. This is an important consideration for those involved in designing effective structured interventions with an MI-informed approach and wanting to maintain fidelity to both MI and the structured programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23019866 Registered 20/4/2009. PMID- 27660555 TI - Robo3A and Robo3B expression is regulated via alternative promoters and mRNA stability. AB - BACKGROUND: The transmembrane receptor family Roundabout (Robo) was described to have an essential role in the developing nervous system. Recent studies demonstrated that Robo3 shows an altered expression in rheumatoid arthritis as well as in melanoma. CONTEXT AND PURPOSE OF THE STUDY: Until today no detailed studies of the two Robo3 isoforms (Robo3A and Robo3B) and their roles in rheumatoid arthritis synovial fibroblasts, respectively malignant melanoma are available. To get a better understanding regarding the role of Robo3A and Robo3B in the molecular process of rheumatoid arthritis and melanoma the exact characterization of expression and regulation is object of this study. RESULTS: mRNA and protein expression of the transcriptional variants were analyzed by quantitative RT-PCR respectively western blotting and revealed particularly enhanced expression of Robo3B in rheumatoid arthritis and melanoma. Promoter assays and inhibitor studies also disclosed that there is apparently a cell- and isoform-specific regulation of the Robo3 expression. Finally, dissimilar mRNA stabilities of Robo3A and Robo3B are identified as decisive posttranscriptional gene expression control. CONCLUSION: In summary, this study supported an isotype specific role of Robo3B in disease hinting to different functional roles of each isoform. PMID- 27660557 TI - Tokenism in patient engagement. AB - Background: Patient engagement throughout research is a way to generate more relevant patient-important research questions, methods and results with the ultimate aim of facilitating translation of research into practice. Tokenism is defined as the practice of making perfunctory or symbolic efforts to engage communities or patients. Objective: We wanted to explore how tokenism might influence engaging patients in research to help researchers work towards more genuine engagement. Methods: The Community Clinician Advisory Group and Patient and Clinician Engagement program held a workshop at the 2015 North American Primary Care Research Group meeting titled 'How Do We Move beyond Tokenism in Patient Engagement?' Patients, clinicians and academic researchers contributed examples of genuine and token engagement characteristics based on personal experience and knowledge. Data were iteratively collated and categorized into domains and items. Results: Examples of genuine and token engagement were categorized into three domains: Methods/Structure of engagement, Intent and Relationship building. Members with experience in patient-engaged research projects felt that longitudinal engagement was a key element to effectively translating research into local community and practice. Conclusions: The group (i) highly valued genuine intent and relationship building as elements to combat tokenism; (ii) noted that early genuine attempts at engagement may superficially resemble tokenism as researchers build enduring and trusting relationships with patient/community partners and (iii) emphasized the importance of seeking and utilizing patient experiences throughout research. These observations may contribute to more formal methods to help researchers (and reviewers) evaluate where engagement processes sit along the 'genuine-token' continuum. PMID- 27660556 TI - Ethnic differences in prevalence and risk factors for hypertension in the Suriname Health Study: a cross sectional population study. AB - BACKGROUND: Limited information is available about the prevalence, ethnic disparities, and risk factors of hypertension within developing countries. We used data from a nationwide study on non-communicable disease (NCD) risk factors to estimate, explore, and compare the prevalence of hypertension overall and in subgroups of risk factors among different ethnic groups in Suriname. METHOD: The Suriname Health Study used the World Health Organization Steps design to select respondents with a stratified multistage cluster sample of households. The overall and ethnic specific prevalences of hypertension were calculated in general and in subgroups of sex, age, marital status, educational level, income status, employment, smoking status, residence, physical activity, body mass index (BMI), and waist circumference (WC). Differences in the prevalence between ethnic subgroups were assessed using the Chi-square test. We used several adjustment models to explore whether the observed ethnic differences were explained by biological, demographic, lifestyle, or anthropometric risk factors. RESULTS: The prevalence of hypertension was 26.2 % (95 % confidence interval 25.1 %-27.4 %). Men had higher mean values for systolic and diastolic blood pressure compared to women. Blood pressure increased with age. The prevalence was highest for Creole, Hindustani, and Javanese and lowest for Amerindians, Mixed, and Maroons. Differences between ethnic groups were measured in the prevalence of hypertension in subcategories of sex, marital status, education, income, smoking, physical activity, and BMI. The major difference in association of ethnic groups with hypertension was between Hindustani and Amerindians. CONCLUSION: The prevalence of hypertension in Suriname was in the range of developing countries. The highest prevalence was found in Creoles, Hindustani, and Javanese. Differences in the prevalence of hypertension were observed between ethnic subgroups with biological, demographic, lifestyle, and anthropometric risk factors. These findings emphasize the need for ethnic-specific research and prevention and intervention programs. PMID- 27660558 TI - Recognition and management of perinatal depression and anxiety by general practitioners: a systematic review. AB - BACKGROUND: Perinatal anxiety and depression are widespread, with up to 20% of women affected during pregnancy and after birth. In the UK, management of perinatal mental health falls under the remit of general practitioners (GPs). We reviewed the literature on GPs' routine recognition, diagnosis and management of anxiety and depression in the perinatal period. METHOD: A systematic search of Embase, Medline, PsycInfo, Pubmed, Scopus and Web of Science was conducted. Studies were eligible if they reported quantitative measures of GPs' or Family Physicians' assessment, recognition and management of anxiety or depression in pregnancy or post-partum. RESULTS: Thirteen papers, reporting 10 studies, were identified from the United States, Australia, UK, Netherlands and Canada. All reported on depression; two included anxiety disorders. Reported awareness and ability to diagnose perinatal depression among GPs was high. GPs knew about and used screening tools in the UK but less so in US settings. Antidepressants were the first line of treatment, with various SSRIs considered safest. Counseling by GPs and referrals to specialists were common in the post-natal period, less so in pregnancy. Treatment choices were determined by resources, attitudes, knowledge and training. CONCLUSIONS: Data on GPs' awareness and management of perinatal depression were sparse and unlikely to be generalizable. Future directions for research are proposed; such as exploring the management of anxiety disorders which are largely missing from the literature, and understanding more about barriers to disclosure and recognition in primary care. More standardized training could help to improve recognition and management practices. PMID- 27660559 TI - Suicidal ideation in a United States jail: Demographic and psychiatric correlates. AB - Suicidal behavior is a significant problem in United States jails. Suicidal ideation (SI) is an established precursor to suicidal behavior in incarcerated populations. No studies to date have examined the prevalence of SI or its correlates in a mixed gender U.S. jail sample. The purpose of the present study was to document rates of SI in a mixed gender jail sample and examine socio demographic and psychiatric correlates. This study of 511 jail inmates found that approximately 16% of participants reported clinically significant SI upon incarceration. White participants, suicide attempters, and those with a psychiatric diagnosis history endorsed greater SI. Reported SI did not differ by sex and was not correlated with age. Clinically, results indicate that screening for SI in jail samples is necessary to identify high-risk individuals for intervention to prevent suicidal behavior. PMID- 27660561 TI - From the Editor's Desk: Ochsner Journal Focus Issue: Cardiovascular Diseases. PMID- 27660560 TI - A Kindler syndrome-associated squamous cell carcinoma treated with radiotherapy. AB - Kindler syndrome1, 2 is a genetic disorder mainly characterized by increased skin fragility and photosensitivity,3, 4 making the use of treatments based on radiation difficult or even prohibited. Thus, cases reporting Kindler syndrome patients treated with radiotherapy are rare. In this study, we report clinical outcomes and care provided for a rare case of a Kindler syndrome patient submitted to radiotherapy. Diagnosed with squamous cell carcinoma involving the buccal mucosa, the patient was exclusively treated with radiotherapy, with 70 Gy delivered on the PTV with the Volumetric Modulated Arc technique. The patient's reaction regarding control of the lesion is relevant compared to patients not affected by the syndrome. We noticed acute reactions of the skin and buccal mucosa after few radiotherapy sessions, followed by a fast reduction in the tumor volume. The efficacy of radiotherapy along with multidisciplinary actions allowed treatment continuity, leading to a complete control of the lesion and life quality improvement and showed that the use of radiotherapy on Kindler syndrome patients is possible. PMID- 27660562 TI - Letters to the Editor. PMID- 27660563 TI - Bioethics in Practice: Considerations for Stopping a Clinical Trial Early. PMID- 27660564 TI - Clinical Images: Vessel Wall Imaging in the Management of Subarachnoid Hemorrhage and Multiple Intracranial Aneurysms. PMID- 27660565 TI - Volume to Value: Defining the Value of Cardiovascular Imaging. PMID- 27660566 TI - Developing Academic Visibility in the Medical Sciences. PMID- 27660567 TI - Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision. AB - BACKGROUND: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. METHODS: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. RESULTS: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. CONCLUSION: Minimally invasive LVAD therapy using the Impella 5.0 via the RSA cutdown is an attractive option in acute on chronic decompensated heart failure. Improvement in end organ function allows for transition to recovery or to advanced surgical therapies such as permanent LVAD and heart transplantation. Significant advantages to this approach include improved left ventricular unloading, lower anticoagulation need, and the potential for ambulation and physical therapy. PMID- 27660568 TI - Cardiovascular Risk and Level of Statin Use Among Women With Breast Cancer in a Cardio-Oncology Clinic. AB - BACKGROUND: Because of the improvements in survival rates, patients with breast cancer are now more likely to die from cardiovascular disease than from cancer. Thus, providing appropriate preventive cardiovascular care to patients with cancer is of the utmost importance. METHODS: We retrospectively compared the cardiovascular risk and management of 146 women treated at the Cardio-Oncology (Cardio-Onc) and the Obstetrics and Gynecology (Ob-Gyn) clinics. We calculated cardiovascular risk using the American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk calculator and the Framingham Risk Score Calculator. We also determined the prevalence of appropriate statin use according to both the 2013 ACC/AHA and the 2002 Adult Treatment Panel (ATP) III lipid guidelines. RESULTS: The 10-year ASCVD risk score was not significantly different between the 2 cohorts. More patients in the Ob Gyn cohort with an ASCVD risk score >7.5% were already appropriately on statins compared to patients in the Cardio-Onc cohort (60.9% vs 31.0%, respectively, P=0.003), but after the first Cardio-Onc visit, 4 additional patients with breast cancer were prescribed statins (44.8% total). Fourteen (19.2%) Cardio-Onc patients had a high Framingham Risk Score compared to 6 (8.2%) Ob-Gyn patients. CONCLUSION: We demonstrated that the ASCVD risk is similar between women with breast cancer attending the Cardio-Onc clinic and the women without breast cancer attending the Ob-Gyn clinic, but the Cardio-Onc cohort had significantly more patients with a high Framingham Risk Score. Both clinics had similarly poor rates of appropriate statin prescribing rates according to the ATP III guidelines. PMID- 27660569 TI - Fluctuating Electrocardiographic Changes Predict Poor Outcomes After Acute Subarachnoid Hemorrhage. AB - BACKGROUND: Electrocardiogram (ECG) abnormalities following aneurysmal subarachnoid hemorrhage (SAH) have been well documented. Evidence suggests that ECG changes and cardiac dysfunction worsen outcome. Determining which patients are at most risk is unclear but important to ascertain. METHODS: We prospectively studied clinical markers, cardiac abnormalities, and clinical outcomes in 20 patients admitted within 48 hours of aneurysmal SAH. All patients had ECGs prior to surgical clipping, during the clipping surgery, and during the postoperative period. RESULTS: The aneurysm was located in the anterior circulation in 17 patients (85%) and in the posterior circulation in 3 patients (15%). Abnormal ECG changes in patients with acute SAH were observed, with a total incidence rate of 65%. The incidence of T wave abnormalities was 53.8% among the patients with ECG changes, 46.2% had ST segment change, and 30.8% had QT interval prolongation. Of the 13 patients with ECG changes, 4 (30.8%) had fluctuating ECG abnormalities (an abnormality that presented and disappeared during the study period or changed in character). All 4 patients with fluctuating ECG changes had a poor outcome (100%) compared to 3 of the 9 patients (33.3%) patients with fixed abnormalities (P<0.05). CONCLUSION: The unique finding in this study that has not been reported previously in the literature is the contribution of dynamic ECG changes to the prognosis for good recovery from aneurysmal SAH. In our group, all the patients who had ECG changes that fluctuated from one abnormal change to another had a poor outcome. The etiology of this finding is not clear but may open the door to further study into the pathogenesis of cardiac changes in aneurysmal SAH. The clinical utility of the variability of ECG abnormalities needs to be validated in a larger cohort of patients with longer follow-up than was possible in this study. PMID- 27660570 TI - A Metaanalysis of Interventions to Improve Adherence to Lipid-Lowering Medication. AB - BACKGROUND: Inadequate patient adherence to a medication regimen is a major factor in the lack of success in treating hyperlipidemia. Improved adherence rates may result in significantly improved cardiovascular outcomes in populations treated with lipid-lowering therapy. The purpose of this metaanalysis was to evaluate the effectiveness of interventions aimed at improving adherence to lipid lowering drugs, focusing on measures of adherence and clinical outcomes. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases through January 14, 2015, and also used the results from previous Cochrane reviews of this title. Randomized controlled trials of adherence enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with measurable outcomes were evaluated with criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Twenty-seven studies randomly assigning 899,068 participants to a variety of interventions were analyzed. One group of interventions categorized as intensified patient care showed significant improvement in adherence rates when compared to usual care (odds ratio 1.93; 95% confidence interval [CI] 1.29-2.88). Additionally, after <6 months of follow-up, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17-33.14), while after >6 months total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95-20.19). CONCLUSION: Healthcare systems that can implement team-based intensified patient care interventions, such as electronic reminders, pharmacist-led interventions, and healthcare professional education of patients, may be successful in improving adherence rates to lipid-lowering medicines. PMID- 27660571 TI - Pacing Without Wires: Leadless Cardiac Pacing. AB - BACKGROUND: Worldwide, more than 700,000 pacemakers are implanted annually with more than 250,000 implanted in the United States. Since the first fully transvenous pacemaker implantations in the early 1960s, great technologic advances have been made in pacing systems. However, the combination of subcutaneous pulse generators and transvenous pacing leads has remained constant for more than 50 years. Leadless pacing systems offer an alternative to traditional pacing systems by eliminating the need for permanent transvenous leads while providing therapy for patients with bradyarrhythmias. METHODS: We discuss the 2 leadless cardiac pacemakers (LCPs), the Nanostim Leadless Pacemaker and Micra Transcatheter Pacing System, and the 1 ultrasound-powered device, the WiCS-LV, that have been studied in humans. Currently LCPs are restricted to single-chamber pacing, specifically, ventricular pacing. Dual-chamber pacing and multichamber pacing with leadless systems have yet to be studied. RESULTS: LCPs represent the greatest advancement in bradycardia therapy since the first transvenous pacemaker implantation more than 50 years ago. CONCLUSION: Initial studies of both the Nanostim and Micra LCPs show favorable efficacy and safety results compared to transvenous pacemakers. Pending US Food and Drug Administration approval, these devices will transform our ability to provide pacing for patients with bradyarrhythmias. Future developments may allow for completely leadless single-chamber and multichamber pacing, ushering in an era of pacing without wires. PMID- 27660572 TI - Percutaneous Ventricular Assist Devices: A Novel Approach in the Management of Patients With Acute Cardiogenic Shock. AB - BACKGROUND: Despite recent advances in the management of heart failure, cardiogenic shock remains a challenging and devastating condition with significant morbidity and mortality. METHODS: We review currently available percutaneous mechanical circulatory support (MCS) devices and address each device's characteristics, mechanism of action, specific clinical indications, and contraindications. RESULTS: Four types of percutaneous MCS devices are currently available: the intraaortic balloon pump (IABP), Impella devices, the TandemHeart, and extracorporal membrane oxygenation (ECMO). IABPs provide less hemodynamic support compared to the Impella, TandemHeart, and ECMO devices. However, because of its ease of placement and relatively small access catheter size, the IABP remains the most commonly used MCS device for the treatment of cardiogenic shock. When full cardiopulmonary support is needed, ECMO is the best option. CONCLUSION: Temporary MCS has emerged as a therapeutic option in the management of patients with acute cardiogenic shock. However, clinician familiarity with the indications, limitations, and benefits of individual MCS devices and enhanced patient comfort with the placement are paramount to improve patient outcomes. PMID- 27660574 TI - Breaking Down the Barriers: Why the Delay in Referral for Pulmonary Arterial Hypertension? AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. While many treatment options have been shown to improve quality of life, exercise tolerance, and hemodynamics in PAH, survival remains poor, in part due to the advanced stage at which patients present to PAH specialists. METHODS: This perspective paper explores challenges related to the timing of referral, diagnosis, and initiation of therapy. RESULTS: Multiple factors account for the delay in referral, including fallacies in physician education, commercial influence resulting in inappropriate prescribing practices, and barriers in access to care. CONCLUSION: Improving physician education, encouraging the prescription of PAH medications to be done predominantly by PAH specialists, overcoming barriers to care, and promoting screening for PAH will help ensure early referral, diagnosis, and treatment. PMID- 27660573 TI - Cardio-Oncology: A Focused Review of Anthracycline-, Human Epidermal Growth Factor Receptor 2 Inhibitor-, and Radiation-Induced Cardiotoxicity and Management. AB - BACKGROUND: Cardio-oncology is a collaborative approach between cardiologists and oncologists in the treatment of patients with cancer and heart disease. Radiation and chemotherapy have played a major role in the decreased cancer-related mortality achieved in the past 2 decades. However, anthracycline-, tyrosine kinase-, and radiation-based therapies are each associated with independent cardiovascular (CV) risks, and these risks are cumulative when these therapies are used in combination. METHODS: We analyzed several published articles, studies, and guidelines to provide a focused review of cardiotoxicity associated with anthracyclines, human epidermal growth factor receptor 2 inhibitors, and radiation therapy and its management. RESULTS: The focus on CV risk among individuals being treated with cardiotoxic agents is important because once the cancer is cured, CV disease becomes the number 1 cause of death among cancer survivors. Cardio-oncology focuses on assessing CV risk prior to starting therapy, optimizing modifiable risk factors, and providing surveillance and treatment for any early signs of cardiotoxicity in patients undergoing radiation and chemotherapy. A collaborative approach between oncologists and cardiologists is integral to the optimal care of patients with cancer. Although radiation and chemotherapy treatments have evolved with the aim of targeting cancer cells while having minimal effect on the heart, the increased risk of cardiomyopathy in patients receiving these treatments remains significant. CONCLUSION: Proper screening and treatment of cardiotoxicity are essential for patients with cancer. As cardiac diseases and cancer remain the first and second causes of mortality in developed nations, respectively, cardio-oncology is the answer to this group of individuals who are especially vulnerable to both causes of mortality. PMID- 27660575 TI - Mechanical Circulatory Support for the Failing Heart: Continuous-Flow Left Ventricular Assist Devices. AB - BACKGROUND: Heart transplantation remains the definitive therapy for patients with advanced heart failure; however, owing to limited donor organ availability and long wait times, continuous-flow left ventricular assist devices (LVADs) have become standard therapy. METHODS: This review summarizes the history, progression, function, and basic management of LVADs. Additionally, we provide some clinical pearls and important caveats for managing this unique patient population. RESULTS: Currently, the most common LVADs being implanted in the United States are second- and third-generation devices, the HeartMate II (Thoratec Corp., St. Jude Medical) and the HeartWare HVAD (HeartWare International, Inc.). A newer third-generation pump, the HeartMate III (Thoratec Corp., St. Jude Medical), is designed to create an artificial pulse and is currently under investigation in the United States. CONCLUSION: LVAD use is promising, will continue to grow, and has become standard therapy for advanced heart failure as a bridge to recovery, as destination therapy, and as a bridge to transplantation. PMID- 27660576 TI - The Evolving Role of Percutaneous Mitral Valve Repair. AB - BACKGROUND: Mitral regurgitation (MR) is the second leading cause of valvular heart disease in the United States behind aortic stenosis. The percutaneous repair of the mitral valve (MitraClip, Abbott, Inc.) has been approved in the United States since 2013 as an alternative to traditional mitral valve surgery. However, many questions are left unanswered about when to perform this procedure and whom to perform it on. METHODS: We reviewed major published literature on the MitraClip from 2003-2016 to help guide clinical decision-making. A PubMed search was conducted using the phrase "mitraclip" or "percutaneous mitral valve repair" to identify relevant articles pertaining to the clip as well as surgical valve repair. RESULTS: The clinical trials EVEREST I and EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) demonstrated the safety and efficacy of the MitraClip but did not prove its superiority to surgical repair in the population studied. Numerous subsequent registries have suggested that the success of the MitraClip varies with the patient population studied. The currently enrolling Cardiovascular Outcomes for Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional MR (COAPT) trial hopes to answer some of these questions. CONCLUSION: The MitraClip is a new and exciting technology for percutaneously treating disease processes traditionally managed with surgery. The future of the clip and its patient population is dependent on further studies. PMID- 27660577 TI - False-Positive Stress Echocardiograms: A Continuing Challenge. AB - BACKGROUND: Stress echocardiography is an integral test in the cardiac diagnostic laboratory and has high sensitivity and specificity. Despite the excellent specificity of stress echocardiography, we continue to see a subset of patients with false-positive tests (defined as <50% diameter stenosis on subsequent coronary angiography). These false-positive findings present a management challenge because it remains unclear if and how to treat these patients. METHODS: This article reviews relevant clinical studies and their outcomes. RESULTS: Studies suggest that a group of patients develops a hypertensive response to exercise and therefore may have false-positive stress echocardiography. Hence, superior blood pressure control prior to stress echocardiography may prevent some false-positive tests. In addition, a subset of patients has microvascular abnormalities, vasomotor changes, endothelial dysfunction, and/or small vessel coronary disease that can lead to false-positive stress echocardiography. CONCLUSION: The evidence is insufficient to state that a false-positive stress echocardiography in the absence of obstructive coronary artery disease portends a poor outcome, but considerable evidence shows that some of these patients have microvascular abnormalities and endothelial dysfunction and consequently may benefit from aggressive medical management and further testing. PMID- 27660579 TI - Catheter Ablation to Treat Supraventricular Arrhythmia in Children and Adults With Congenital Heart Disease: What We Know and Where We Are Going. AB - BACKGROUND: Catheter ablation has been used to manage supraventricular arrhythmia in children since 1990. This article reviews the history of catheter ablation used to treat arrhythmia in children and discusses new frontiers in the field. We also address ablation in adult patients with a history of congenital heart disease (CHD) that was diagnosed and initially treated in childhood. METHODS: We conducted an evidence-based literature review to gather available data on ablation for supraventricular tachycardia in children and adult patients with CHD. RESULTS: Ablations can be performed safely and effectively in children. Complication rates are higher in children <4 years and <15 kg. In one study, the overall success rate of radiofrequency ablation in pediatrics was 95.7%, with the highest success rate in left free wall pathways (97.8%). Recurrence was higher in septal pathways. Cryoablation has been reported to have a 93% acute success rate for atrioventricular (AV) nodal reentrant tachycardia and septal pathways with no risk of AV block and a 5%-9% risk of recurrence. Three-dimensional mapping, intracardiac echocardiography, remote magnetic navigation, and irrigated catheter ablation are new technologies used to treat pediatric and adult patients with CHD. The population of adult patients with CHD is growing, and these patients are at particularly high risk for arrhythmia. A paucity of data is available on ablation in adult patients with CHD. CONCLUSION: Electrophysiology for pediatric and adult patients with CHD is a rapidly growing and progressing field. We benefit from continuous development of ablation techniques for adults with structurally normal hearts and have the unique challenge and responsibility to ensure the safe and effective application of these techniques in the vulnerable population of pediatric and adult patients with CHD. PMID- 27660578 TI - Surface Electrocardiogram Predictors of Sudden Cardiac Arrest. AB - BACKGROUND: Heart disease is a major cause of death in industrialized nations, with approximately 50% of these deaths attributable to sudden cardiac arrest. If patients at high risk for sudden cardiac arrest can be identified, their odds of surviving fatal arrhythmias can be significantly improved through prophylactic implantable cardioverter defibrillator placement. This review summarizes the current knowledge pertaining to surface electrocardiogram (ECG) predictors of sudden cardiac arrest. METHODS: We conducted a literature review focused on methods of predicting sudden cardiac arrest through noninvasive electrocardiographic testing. RESULTS: Several electrocardiographic-based methods of risk stratification of sudden cardiac arrest have been studied, including QT prolongation, QRS duration, fragmented QRS complexes, early repolarization, Holter monitoring, heart rate variability, heart rate turbulence, signal-averaged ECG, T wave alternans, and T-peak to T-end. These ECG findings have shown variable effectiveness as screening tools. CONCLUSION: At this time, no individual ECG finding has been found to be able to adequately stratify patients with regard to risk for sudden cardiac arrest. However, one or more of these candidate surface ECG parameters may become useful components of future multifactorial risk stratification calculators. PMID- 27660581 TI - Chagas Cardiomyopathy in New Orleans and the Southeastern United States. AB - BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, affects 6-7 million people worldwide annually, primarily in Central and South America, and >300,000 people in the United States. CD consists of acute and chronic stages. Hallmarks of acute CD include fever, myalgia, diaphoresis, hepatosplenomegaly, and myocarditis. Symptoms of chronic CD include pathologic involvement of the heart, esophagus, and colon. Myocardial involvement is identifiable by electrocardiogram and cardiac magnetic resonance imaging showing inflammation and left ventricular wall functional abnormalities. CASE REPORTS: We present two cases of CD identified in a single hospital in the Southeastern United States. Case 1 presents a patient with symptoms of anginal chest pain and associated shortness of breath with myocardial involvement suggestive of ischemic infarction but normal coronary arteries. Case 2 describes a patient with no physical symptoms and echocardiogram with ejection fraction of 50% with posterolateral and anterolateral wall hypokinesis but normal coronary arteries. CONCLUSION: With a growing number of immigrants from Central and South America in the United States, it is imperative for clinicians to include CD as part of the differential diagnosis for patients presenting with heart disease who have a history of exposure to T. cruzi endemic areas. PMID- 27660580 TI - The Exercise Rehabilitation Paradox: Less May Be More? AB - BACKGROUND: Debatably, the most commonly prescribed lifestyle modification for cardiovascular health involves daily exercise training (ET) and physical activity. Exercise has numerous known health benefits on blood pressure, lipid profile, weight loss, and glucose metabolism. However, controversy exists regarding the link between excessive endurance ET and harmful cardiac effects. METHODS: We review the current literature and discuss the numerous known adverse effects of endurance ET on cardiac function. RESULTS: Excessive endurance ET may negatively affect cardiac anatomy, play a role in osteoarthritis and coronary artery disease development, and increase the risks of cardiac arrhythmia and sudden cardiac death. CONCLUSION: More ET may not always be better when it comes to endurance ET, and optimal ET dosing regimens are clearly needed. PMID- 27660582 TI - Pulmonary Hypertension in a Patient With Congenital Heart Defects and Heterotaxy Syndrome. AB - BACKGROUND: Heterotaxy syndrome, also called isomerism, is a condition in which abdominal and thoracic organs are located in abnormal body positions. Pulmonary hypertension (PHTN) is an uncommon clinical feature of heterotaxy syndrome. CASE REPORT: We describe the case of a 26-year-old male who developed PHTN as a rare manifestation of heterotaxy syndrome. To our knowledge, PHTN has never been reported as a prominent clinical feature in a patient with heterotaxy syndome and congenital cardiac abnormalities. CONCLUSION: It is important for the clinician to be aware of potentially serious consequences of PHTN in the setting of heterotaxy syndrome. PMID- 27660583 TI - Two Cases of Acute Renal Infarction in the Setting of Atrial Fibrillation. AB - BACKGROUND: Acute renal infarction (ARI) is an uncommon and often overlooked diagnosis in patients presenting with acute kidney injury and abdominal pain. CASE REPORTS: We present 2 cases of ARI in the setting of atrial fibrillation along with a review of medical literature pertaining to ARI. CONCLUSION: This article should aid clinicians in the diagnosis of ARI. PMID- 27660584 TI - Postinduction Paced Pulseless Electrical Activity in a Patient With a History of Oropharyngeal Instrumentation-Induced Reflex Circulatory Collapse. AB - BACKGROUND: Reflex hypotension and bradycardia have been reported to occur following administration of several drugs associated with administration of anesthesia and also following a variety of procedural stimuli. CASE REPORT: A 54 year-old postmenopausal female with a history of asystole associated with sedated upper gastrointestinal endoscopy and post-anesthetic-induction tracheal intubation received advanced cardiac resuscitation after insertion of a temporary transvenous pacemaker failed to prevent pulseless electrical activity. The patient's condition stabilized, and she underwent successful cataract extraction, intraocular lens implantation, and pars plana vitrectomy. CONCLUSION: Cardiac pacemaker insertion prior to performance of a procedure historically associated with reflex circulatory collapse can be expected to protect a patient from bradycardia but not necessarily hypotension. PMID- 27660585 TI - Thromboembolism-in-Transit and Patent Foramen Ovale: Should Screening Echocardiogram Be Routine for Thromboembolic Disease? AB - BACKGROUND: Thromboembolism-in-transit straddling a patent foramen ovale (PFO) is a rare condition that requires urgent surgical intervention to prevent arterial emboli. CASE REPORT: We present the case of a 42-year-old female who presented with a symptomatic pulmonary embolism. Echocardiography identified a PFO, with a bridging thrombus-in-transit and evidence of right ventricular strain. Urgent surgery was performed because of the risk of systemic embolism. A large thrombus was identified during biatrial exploration. Pulmonary embolectomy and primary PFO closure were performed. CONCLUSION: Because of the 20%-30% incidence of PFOs in the general population, we suggest that echocardiography should be considered for routine surveillance in thromboembolism because of the risk of systemic sequelae. PMID- 27660587 TI - Ochsner Research Update, 2015-2016. PMID- 27660586 TI - Metastatic Cardiac Angiosarcoma in a 26-Year-Old Male. AB - BACKGROUND: Cardiac angiosarcomas are an extremely rare tumor with an incidence of only 0.056%. Diagnosing this rare tumor becomes even more difficult as the presentation of cardiac angiosarcomas varies based on anatomic location. Depending on the tumor's proximity to valves, symptoms may be more consistent with heart failure, while growth throughout the conduction system may produce arrhythmias. CASE REPORT: We present the case of a young male with a significant tumor burden of cardiac angiosarcoma in his lungs whose symptoms included pleuritic chest pain and hemoptysis. This patient did not have the classic finding of right-sided heart failure; instead, his presenting complaint was hemoptysis. CONCLUSION: The diagnostician's differential diagnosis must be broad when encountering common chief complaints, such as hemoptysis and chest pain. PMID- 27660588 TI - Introduction to Ochsner's Thirteenth Annual Research Day. PMID- 27660589 TI - Research Day 2016 Award Winners. PMID- 27660591 TI - Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems. AB - Secondary ion mass spectrometry (SIMS) is a technique capable of imaging tissues, single cells, and microbes revealing chemical species with sub-micrometer spatial resolution. The recently developed Fourier transform ion cyclotron resonance (FTICR) SIMS instrument provides high mass resolving power and mass accuracy, ToF SIMS can generate chemical maps with an order of magnitude better lateral resolution than the FTICR-SIMS, and the NanoSIMS instrument offers sub-100 nm spatial resolution in chemical imaging. Many commercial ToF-SIMS instruments are also capable of depth profiling that allows three-dimensional reconstructions of cell and tissue structure. PMID- 27660590 TI - Violent Victimization and Substance Dependency: Comparing Rural Incarcerated Heterosexual and Sexual Minority Women. AB - This exploratory study examines the relationship between sexual identity and violent victimization experiences as predictors of differences in illicit substance and alcohol use and substance use problems among a sample of incarcerated women in rural Appalachia (N = 400). Results indicated that, compared to heterosexual women, sexual minority women were more likely to have a lifetime history of weapon, physical, and sexual assault, and were younger at the time of their first violent victimization. Sexual minority women were younger than heterosexual women at the age of onset for intravenous drug use and at the time they first got drunk, and were more likely to report having overdosed. Multivariate analysis found violent victimization to be the strongest predictor of a history of overdose and substance use problems. PMID- 27660592 TI - Treatment of Hepatitis C Virus Genotype 3 Infection. PMID- 27660594 TI - Therapeutic Benefits of l-Arginine: An Umbrella Review of Meta-analyses. AB - OBJECTIVE: l-Arginine is a semi-essential amino acid that is the substrate for nitric oxide production by vascular endothelial and immune cells. Nitric oxide production by these cells is essential for both blood pressure regulation and immune regulation. However, there is much discrepancy in the literature when it comes to randomized controlled studies, and so this umbrella review of published meta-analyses was performed to examine the efficacy of l-arginine's role as a therapeutic agent. METHODS: There was an overall search of the literature from January 1, 1980 through December 31, 2015 of three separate databases-PubMed, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature using the following search strategy: (arginine) AND (meta-analysis OR systematic review). Only English language publications were retrieved that provided quantitative statistical analysis of outcomes on blood pressure and immune function. RESULTS: The 7 meta-analyses that were included in this umbrella review reported significant positive benefits for reducing systolic and diastolic blood pressure in hypertensive adults by 2.2 to 5.4 mm Hg and 2.7 to 3.1 mm Hg, respectively, reducing diastolic blood pressure in pregnant women with gestational hypertension by 4.9 mm Hg, and reducing the length of stay in the hospital for surgical patients; in addition, 2 of the 3 meta-analyses indicated a 40% reduction in the incidence of hospital-acquired infections. However, these positive results should be considered with caution because statistically significant heterogeneity was observed in 5 of the 7 meta-analyses. CONCLUSIONS: Some evidence appears to support the benefit of l-arginine supplementation for reducing systolic and diastolic blood pressure in hypertensive adults and reducing the incidence of hospital-acquired infections and the length of stay in the hospital for surgical patients. Given the limitations of the included studies, interpretations should be made with caution. PMID- 27660593 TI - Spinal Manipulation Vs Sham Manipulation for Nonspecific Low Back Pain: A Systematic Review and Meta-analysis. AB - OBJECTIVE: The purpose of this systematic review was to identify and critically evaluate randomized controlled trials of spinal manipulation (SM) vs sham manipulation in the treatment of nonspecific low back pain. METHODS: Four electronic databases were searched from their inception to March 2015 to identify all relevant trials. Reference lists of retrieved articles were hand-searched. All data were extracted by 2 independent reviewers, and risk of bias was assessed using the Cochrane Back Review Group Risk of Bias tool. RESULTS: Nine randomized controlled trials were included in the systematic review, and 4 were found to be eligible for inclusion in a meta-analysis. Participants in the SM group had improved symptoms compared with participants receiving sham treatment (standardized mean difference = - 0.36; 95% confidence interval, - 0.59 to - 0.12). The majority of studies were of low risk of bias; however, several of the studies were small, the practitioner could not be blinded, and some studies did not conduct intention-to-treat analysis and had a high level of dropouts. CONCLUSION: There is some evidence that SM has specific treatment effects and is more effective at reducing nonspecific low back pain when compared with an effective sham intervention. However, given the small number of studies included in this analysis, we should be cautious of making strong inferences based on these results. PMID- 27660596 TI - Effect of TENS Versus Placebo on Walking Capacity in Patients With Lumbar Spinal Stenosis: A Protocol for a Randomized Controlled Trial. AB - BACKGROUND: Lumbar spinal stenosis (LSS) is a growing health problem and a leading cause of disability and loss of independence in older adults. It is usually caused by age-related degenerative narrowing of the spinal canals leading to compression and ischemia of the spinal nerves and symptoms of neurogenic claudication. Limited walking ability is the dominant functional impairment caused by LSS. Animal studies suggest increased blood flow to the spinal nerves and spinal cord with superficial paraspinal electrical stimulation. The purpose of this study is to assess the effectiveness of paraspinal transcutaneous electrical nerve stimulation (TENS) applied while walking on walking ability in patients with LSS. METHODS/DESIGN: We propose to conduct a 2-arm double-blinded (participant and assessor) randomized controlled trial. We will recruit individuals who have limited walking ability due to degenerative LSS from hospital specialists, community physicians, and chiropractors located in the city of Toronto, Canada. Eligible consenting participants will be randomly assigned to either paraspinal TENS or placebo paraspinal TENS applied while walking. The primary outcome will be walking distance measured during a single self-paced walking test. We will calculate the differences in proportions among participants in both groups who achieve at least a 30% improvement in walking distance from baseline using Pearson chi (2) test with 95% confidence intervals. DISCUSSION: Effective nonoperative interventions for LSS are unknown. Interventions that can improve blood flow to the spinal nerves while walking may increase walking ability in this population. Transcutaneous electrical nerve stimulation is a low cost intervention that may have the potential to achieve this objective. To our knowledge, this study will be the first clinical trial to assess the effects of TENS on walking ability of patients with LSS. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02592642. PMID- 27660597 TI - One-Year Concussion Prevalence in Marion County, Florida High School Athletes. AB - OBJECTIVE: The purpose of this study was to evaluate data on concussion prevalence in 1 geographic location and to identify which sports have a higher prevalence of concussion in the Marion County, Florida, school district. METHODS: High school athletic trainers in Marion County, Florida, are required to compile statistics related to number of participants and concussions sustained in the county school district during each season. They provided the data for the 2011 2012 school year to independent analysts with the permission of the athletic director. The study evaluated 3689 student-athletes (2102 male, 1587 female), and 34 concussions (24 male, 10 female) were reported. Concussions were self-reported by the athletes and diagnosed by trainers on field or by follow-up after physician referral. Consent was included in consent to participate in interscholastic athletics, and all athletes enrolling in a sport during the 2011 2012 academic year were included regardless of participation level. Number of participants and concussions sustained was calculated per 100 participants for each sport and in total for 1 year. RESULTS: The percentages of concussions per sport were as follows: basketball, 1.83%; cheerleading, 0.40%; football, 2.83%; soccer, 1.84%; track and field, 0.44%; and wrestling, 0.70%. Ten additional sports were included in the study but had no reported concussions. Total prevalence for the district was 0.922% (1.14% male, 0.63% female) during a 1-year period. CONCLUSION: The concussion prevalence in this district during the 2011 2012 school year was just under 1%. The sport reporting the highest prevalence was football, followed by soccer. Females reported a higher rate of concussions than males in sports played by both male and female participants. This highlights the need to minimize risk for concussion, especially in noncollision contact sports, and in female athletes. PMID- 27660595 TI - The Physiological Role of Tumor Necrosis Factor in Human Immunity and Its Potential Implications in Spinal Manipulative Therapy: A Narrative Literature Review. AB - OBJECTIVE: Although tumor necrosis factor (TNF) is a well-known inflammatory cytokine in the pathological development of various human diseases, its physiological roles are not widely understood nor appreciated. The molecular mechanisms underlying spinal manipulation therapy (SMT) remain elusive. The relationship between TNF and SMT is unclear. Thus, we performed this literature review to better understand TNF physiology and its potential relationship with SMT, and we propose a novel mechanism by which SMT may achieve clinical benefits by using certain beneficial features of TNF. METHODS: We searched several databases for relevant articles published between 1975 and 2015 and then reexamined the studies from current immunophysiological perspectives. RESULTS: The history and recent progresses in TNF physiology research were explored. Conflicting reports on the relationship between TNF and SMT were identified. Based on the newly discovered interaction between TNF and regulatory T cells, we proposed a putative biphasic TNF response to SMT, which may resolve the conflicts in the reported observations and interpretations. CONCLUSION: The current literature about TNF informed our discussion of new physiological roles for TNF, which may help to better understand the physiological effects of SMT. PMID- 27660599 TI - Sonographic and Magnetic Resonance Imaging Examination of a Cyclops Lesion After Anterior Cruciate Ligament Reconstruction: A Case Report. AB - OBJECTIVE: This case report describes magnetic resonance imaging (MRI) and diagnostic ultrasound (US) findings for a patient with arthrofibrosis related to a complication of anterior cruciate ligament (ACL) reconstruction. CLINICAL FEATURES: A 25-year old man presented with right knee pain and loss of extension 5 years after ACL reconstruction. MRI and sonographic examination revealed a soft tissue mass anterolateral to the ACL graft consistent with a cyclops lesion. The lesion was surgically resected and physical therapy was followed postoperatively. INTERVENTION AND OUTCOME: The patient reported that full range of motion was restored 6 weeks after resection and a course of physical therapy. MRI is the modality of choice for diagnosis, but US may be useful in the diagnosis of this condition. CONCLUSION: Cyclops lesions may complicate ACL reconstruction or acute ACL injuries. The patient may present with pain and loss of extension, which can be debilitating. MRI and US can be used to diagnose this condition in a timely manner, ensuring optimal clinical outcomes. PMID- 27660598 TI - Chiropractic Management of Musculoskeletal Symptoms in a 14-Year-Old Hockey Player With Postconcussion Symptoms: A Case Report. AB - OBJECTIVE: The purpose of this study is to describe the chiropractic management of a student athlete with postconcussion syndrome. CLINICAL FEATURES: A 14-year old male hockey player presented to a chiropractic clinic with postconcussion symptoms 13 days after his initial injury. He experienced an occipital headache with a pain rating of 8/10, upset stomach, blurry vision, nausea, dizziness, balance problems, a "foggy feeling," difficulty with concentration, difficulty with memory, fatigue, confusion, drowsiness, and irritability. Prior to seeing the doctor of chiropractic, the patient was monitored by a medical doctor, and the care he had been receiving was in accordance with current concussion guidelines. At the time of presentation to the chiropractic clinic, he had failed to progress toward return to play, and his computerized neurocognitive testing scores had not improved. INTERVENTION AND OUTCOME: Chiropractic manipulative therapy, myofascial release, instrument-assisted soft tissue technique, and therapeutic exercises were provided over 5 treatments spanning a 20-day period. The patient followed up each treatment with ImPACT testing. At the conclusion of the treatments, the patient's computerized neurocognitive testing scores had improved, and the patient was returned to play. CONCLUSION: This case demonstrates the improvement of postconcussion syndrome in a 14-year-old male hockey player under chiropractic management. PMID- 27660600 TI - Calcium Pyrophosphate Dihydrate Crystal Deposition Disease Simulating Osteoarthrosis of the Knee: A Case Report. AB - OBJECTIVE: The purpose of this case report is to describe a case where calcium pyrophosphate dehydrate crystal deposition disease (CPPD) simulated osteoarthritis of the knee. CLINICAL FEATURES: A 78-year-old woman had a 2-week history of severe right knee pain accompanied by mild swelling. The onset was sudden and did not involve a history of trauma or previous injury to the right knee. Inspection and palpation revealed pain along the medial joint line and marked difficulty ambulating. Results of Lachman's test, anterior drawer test, and posterior sag sign were negative upon orthopedic assessment. Diagnostic imaging was performed and showed degenerative changes with diffuse calcification of the fibrocartilage and hyaline articular cartilage within the knee joint and the medial collateral ligament consistent with the appearance of CPPD crystal deposition. INTERVENTION AND OUTCOME: Low-level laser therapy was performed to the affected medial joint line of the knee, and knee stabilization exercises were given. Lower Extremity Function Scale changed from 34% to 60% after 4 weeks of care. CONCLUSION: Although knee osteoarthritis is much more common than knee CPPD, it is important to consider both diagnoses in elderly patients who present with unilateral knee pain. Diagnosis should be based on clinical presentation, history, and radiographic or histological means to ensure accuracy and proper diagnosis. PMID- 27660601 TI - Effect of Ag Addition on the Electrochemical Performance of Cu10Al in Artificial Saliva. AB - In this work we proposed to evaluate the corrosion resistance of four different alloys by electrochemical techniques, a binary alloy Cu10Al, and three ternary alloys Cu10Al-xAg (x = 5, 10, and 15 wt.%) to be used like biomaterials in dental application. Biomaterials proposed were tested in artificial saliva at 37 degrees C for 48 h. In addition, pure metals Cu, Al, Ag, and Ti as reference materials were evaluated. In general the short time tests indicated that the Ag addition increases the corrosion resistance and reduces the extent of localized attack of the binary alloy. Moreover, tests for 48 hours showed that the Ag addition increases the stability of the passive layer, thereby reducing the corrosion rate of the binary alloy. SEM analysis showed that Cu10Al alloy was preferably corroded by grain boundaries, and the Ag addition modified the form of attack of the binary alloy. Cu-rich phases reacted with SCN(-) anions forming a film of CuSCN, and the Ag-rich phase is prone to react with SCN(-) anions forming AgSCN. Thus, binary and ternary alloys are susceptible to tarnish in the presence of thiocyanate ions. PMID- 27660602 TI - Capacitive Feedthroughs for Medical Implants. AB - Important technological advances in the last decades paved the road to a great success story for electrically stimulating medical implants, including cochlear implants or implants for deep brain stimulation. However, there are still many challenges in reducing side effects and improving functionality and comfort for the patient. Two of the main challenges are the wish for smaller implants on one hand, and the demand for more stimulation channels on the other hand. But these two aims lead to a conflict of interests. This paper presents a novel design for an electrical feedthrough, the so called capacitive feedthrough, which allows both reducing the size, and increasing the number of included channels. Capacitive feedthroughs combine the functionality of a coupling capacitor and an electrical feedthrough within one and the same structure. The paper also discusses the progress and the challenges of the first produced demonstrators. The concept bears a high potential in improving current feedthrough technology, and could be applied on all kinds of electrical medical implants, even if its implementation might be challenging. PMID- 27660603 TI - Magnitude of Morning Surge in Blood Pressure Is Associated with Sympathetic but Not Cardiac Baroreflex Sensitivity. AB - The ability of the arterial baroreflex to regulate blood pressure may influence the magnitude of the morning surge in blood pressure (MSBP). The aim was to investigate the relationships between sympathetic and cardiac baroreflex sensitivity (BRS) and the morning surge. Twenty-four hour ambulatory blood pressure was recorded in 14 young individuals. The morning surge was defined via the pre-awakening method, which is calculated as the difference between mean blood pressure values 2 h before and 2 h after rising from sleep. The mean systolic morning surge, diastolic morning surge, and morning surge in mean arterial pressures were 15 +/- 2, 13 +/- 1, and 11 +/- 1 mmHg, respectively. During the laboratory protocol, continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made over a 10-min period of rest. Sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (sympathetic BRStotal). Cardiac BRS was quantified using the sequence method. The mean values for sympathetic BRSinc, sympathetic BRStotal and cardiac BRS were -1.26 +/- 0.26 bursts/100 hb/mmHg, -1.60 +/- 0.37 AU/beat/mmHg, and 13.1 +/- 1.5 ms/mmHg respectively. Significant relationships were identified between sympathetic BRSinc and the diastolic morning surge (r = 0.62, p = 0.02) and the morning surge in mean arterial pressure (r = 0.57, p = 0.03). Low sympathetic BRS was associated with a larger morning surge in mean arterial and diastolic blood pressure. Trends for relationships were identified between sympathetic BRStotal and the diastolic morning surge (r = 0.52, p = 0.066) and the morning surge in mean arterial pressure (r = 0.48, p = 0.095) but these did not reach significance. There were no significant relationships between cardiac BRS and the morning surge. These findings indicate that the ability of the baroreflex to buffer increases in blood pressure via reflexive changes in MSNA may play a role in determining the magnitude of the MSBP. PMID- 27660604 TI - Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality. AB - Adolescent obesity is associated with an increased chance of developing serious health risks later in life. Identifying the neurobiological and personality factors related to increases in adiposity is important to understanding what drives maladaptive consummatory and exercise behaviors that result in obesity. Previous research has largely focused on adults with few findings published on interactions among adiposity, brain structure, and personality. In this study, Voxel Based Morphometry (VBM) was used to identify associations between gray and white matter volumes and increasing adiposity, as measured by Body Mass Index percentile (BMI%), in 137 adolescents (age range: 9-20 years, BMI% range: 5.16 99.56). Variations in gray and white matter volume and BMI% were then linked to individual differences in personality measures from the Multidimensional Personality Questionnaire (MPQ). After controlling for age and other covariates, BMI% correlated negatively with gray matter volume in the bilateral caudate (right: partial r = -0.338, left: r = -0.404), medial prefrontal cortex (partial r = -0.339), anterior cingulate (partial r = -0.312), bilateral frontal pole (right: partial r = -0.368, left: r = -0.316), and uncus (partial r = -0.475) as well as white matter volume bilaterally in the anterior limb of the internal capsule (right: partial r = -0.34, left: r = -0.386), extending to the left middle frontal subgyral white matter. Agentic Positive Emotionality (PEM-AG) was correlated negatively with BMI% (partial r = -0.384). PEM-AG was correlated positively with gray matter volume in the right uncus (partial r = 0.329). These results suggest that higher levels of adiposity in adolescents are associated with lower trait levels in reward-related personality domains, as well as structural variations in brain regions associated with reward processing, control, and sensory integration. PMID- 27660605 TI - Lettuce and rhizosphere microbiome responses to growth promoting Pseudomonas species under field conditions. AB - Plant growth promoting rhizobacteria are well described and recommended for several crops worldwide. However, one of the most common problems in research into them is the difficulty in obtaining reproducible results. Furthermore, few studies have evaluated plant growth promotion and soil microbial community composition resulting from bacterial inoculation under field conditions. Here we evaluated the effect of 54 Pseudomonas strains on lettuce (Lactuca sativa) growth. The 12 most promising strains were phylogenetically and physiologically characterized for plant growth-promoting traits, including phosphate solubilization, hormone production and antagonism to pathogen compounds, and their effect on plant growth under farm field conditions. Additionally, the impact of beneficial strains on the rhizospheric bacterial community was evaluated for inoculated plants. The strains IAC-RBcr4 and IAC-RBru1, with different plant growth promoting traits, improved lettuce plant biomass yields up to 30%. These two strains also impacted rhizosphere bacterial groups including Isosphaera and Pirellula (phylum Planctomycetes) and Acidothermus, Pseudolabrys and Singusphaera (phylum Actinobacteria). This is the first study to demonstrate consistent results for the effects of Pseudomonas strains on lettuce growth promotion for seedlings and plants grown under tropical field conditions. PMID- 27660607 TI - Nitrogen cycling process rates across urban ecosystems. AB - Nitrogen (N) pollution of freshwater, estuarine, and marine ecosystems is widespread and has numerous environmental and economic impacts. A portion of this excess N comes from urban watersheds comprised of natural and engineered ecosystems which can alter downstream N export. Studies of urban N cycling have focused on either specific ecosystems or on watershed-scale mass balances. Comparisons of specific N transformations across ecosystems are required to contextualize rates from individual studies. Here we reviewed urban N cycling in terrestrial, aquatic, and engineered ecosystems, and compared N processing in these urban ecosystem types to native reference ecosystems. We found that net N mineralization and net nitrification rates were enhanced in urban forests and riparian zones relative to reference ecosystems. Denitrification was highly variable across urban ecosystem types, but no significant differences were found between urban and reference denitrification rates. When focusing on urban streams, ammonium uptake was more rapid than nitrate uptake in urban streams. Additionally, reduction of stormwater runoff coupled with potential decreases in N concentration suggests that green infrastructure may reduce downstream N export. Despite multiple environmental stressors in urban environments, ecosystems within urban watersheds can process and transform N at rates similar to or higher than reference ecosystems. PMID- 27660606 TI - Genomic insights into metabolic versatility of a lithotrophic sulfur-oxidizing diazotrophic Alphaproteobacterium Azospirillum thiophilum. AB - Diazotrophic Alphaproteobacteria of the genus Azospirillum are usually organotrophs, although some strains of Azospirillum lipoferum are capable of hydrogen-dependent autotrophic growth. Azospirillum thiophilum strain was isolated from a mineral sulfide spring, a biotope highly unusual for azospirilla. Here, the metabolic pathways utilized by A. thiophilum were revealed based on comprehensive analysis of its genomic organization, together with physiological and biochemical approaches. The A. thiophilum genome contained all the genes encoding the enzymes of carbon metabolism via glycolysis, tricarboxylic acid cycle and glyoxylate cycle. Genes for a complete set of enzymes responsible for autotrophic growth, with an active Calvin-Benson-Bassham cycle, were also revealed, and activity of the key enzymes was determined. Microaerobic chemolithoautotrophic growth of A. thiophilum was detected in the presence of thiosulfate and molecular hydrogen, being in line with the discovery of the genes encoding the two enzymes involved in dissimilatory thiosulfate oxidation, the Sox complex and thiosulfate dehydrogenase and Ni-Fe hydrogenases. Azospirillum thiophilum utilizes methanol and formate, producing CO2 that can further be metabolized via the Calvin cycle. Finally, it is capable of anaerobic respiration, using tetrathionate as a terminal electron acceptor. Such metabolic versatility is of great importance for adaptation of A. thiophilum to constantly changing physicochemical environment. PMID- 27660608 TI - Distribution of Response Time, Cortical, and Cardiac Correlates during Emotional Interference in Persons with Subclinical Psychotic Symptoms. AB - A psychosis phenotype can be observed below the threshold of clinical detection. The study aimed to investigate whether subclinical psychotic symptoms are associated with deficits in controlling emotional interference, and whether cortical brain and cardiac correlates of these deficits can be detected using functional near-infrared spectroscopy (fNIRS). A data set derived from a community sample was obtained from the Zurich Program for Sustainable Development of Mental Health Services. 174 subjects (mean age 29.67 +/- 6.41, 91 females) were assigned to four groups ranging from low to high levels of subclinical psychotic symptoms (derived from the Symptom Checklist-90-R). Emotional interference was assessed using the emotional Stroop task comprising neutral, positive, and negative conditions. Statistical distributional methods based on delta plots [behavioral response time (RT) data] and quantile analysis (fNIRS data) were applied to evaluate the emotional interference effects. Results showed that both interference effects and disorder-specific (i.e., group-specific) effects could be detected, based on behavioral RTs, cortical hemodynamic signals (brain correlates), and heart rate variability (cardiac correlates). Subjects with high compared to low subclinical psychotic symptoms revealed significantly reduced amplitudes in dorsolateral prefrontal cortices (interference effect, p < 0.001) and middle temporal gyrus (disorder-specific group effect, p < 0.001), supported by behavioral and heart rate results. The present findings indicate that distributional analyses methods can support the detection of emotional interference effects in the emotional Stroop. The results suggested that subjects with high subclinical psychosis exhibit enhanced emotional interference effects. Based on these observations, subclinical psychosis may therefore prove to represent a valid extension of the clinical psychosis phenotype. PMID- 27660609 TI - Presence of a Chaotic Region at the Sleep-Wake Transition in a Simplified Thalamocortical Circuit Model. AB - Sleep and wakefulness are characterized by distinct states of thalamocortical network oscillations. The complex interplay of ionic conductances within the thalamo-reticular-cortical network give rise to these multiple modes of activity and a rapid transition exists between these modes. To better understand this transition, we constructed a simplified computational model based on physiological recordings and physiologically realistic parameters of a three neuron network containing a thalamocortical cell, a thalamic reticular neuron, and a corticothalamic cell. The network can assume multiple states of oscillatory activity, resembling sleep, wakefulness, and the transition between these two. We found that during the transition period, but not during other states, thalamic and cortical neurons displayed chaotic dynamics, based on the presence of strange attractors, estimation of positive Lyapunov exponents and the presence of a fractal dimension in the spike trains. These dynamics were quantitatively dependent on certain features of the network, such as the presence of corticothalamic feedback and the strength of inhibition between the thalamic reticular nucleus and thalamocortical neurons. These data suggest that chaotic dynamics facilitate a rapid transition between sleep and wakefulness and produce a series of experimentally testable predictions to further investigate the events occurring during the sleep-wake transition period. PMID- 27660610 TI - Structural Plasticity Denoises Responses and Improves Learning Speed. AB - Despite an abundance of computational models for learning of synaptic weights, there has been relatively little research on structural plasticity, i.e., the creation and elimination of synapses. Especially, it is not clear how structural plasticity works in concert with spike-timing-dependent plasticity (STDP) and what advantages their combination offers. Here we present a fairly large-scale functional model that uses leaky integrate-and-fire neurons, STDP, homeostasis, recurrent connections, and structural plasticity to learn the input encoding, the relation between inputs, and to infer missing inputs. Using this model, we compare the error and the amount of noise in the network's responses with and without structural plasticity and the influence of structural plasticity on the learning speed of the network. Using structural plasticity during learning shows good results for learning the representation of input values, i.e., structural plasticity strongly reduces the noise of the response by preventing spikes with a high error. For inferring missing inputs we see similar results, with responses having less noise if the network was trained using structural plasticity. Additionally, using structural plasticity with pruning significantly decreased the time to learn weights suitable for inference. Presumably, this is due to the clearer signal containing less spikes that misrepresent the desired value. Therefore, this work shows that structural plasticity is not only able to improve upon the performance using STDP without structural plasticity but also speeds up learning. Additionally, it addresses the practical problem of limited resources for connectivity that is not only apparent in the mammalian neocortex but also in computer hardware or neuromorphic (brain-inspired) hardware by efficiently pruning synapses without losing performance. PMID- 27660612 TI - Functional Segregation within the Muscles of Aquatic Propulsion in the Asiatic Water Monitor (Varanus salvator). AB - Water monitor lizards (Varanus salvator) swim using sinusoidal oscillations generated at the base of their long (50% of total body length) tail. In an effort to determine which level of the structural/organizational hierarchy of muscle is associated with functional segregation between the muscles of the tail base, an array of muscle features-myosin heavy chain profiles, enzymatic fiber types, twitch and tetanic force production, rates of fatigue, muscle compliance, and electrical activity patterns-were quantitated. The two examined axial muscles, longissimus, and iliocaudalis, were generally similar at the molecular, biochemical, and physiological levels, but differed at the biomechanics level and in their activation pattern. The appendicular muscle examined, caudofemoralis, differed from the axial muscles particularly at the molecular and physiological levels, and it exhibited a unique compliance profile and pattern of electrical activation. There were some apparent contradictions between the different structural/organizational levels examined. These contradictions, coupled with a unique myosin heavy chain profile, lead to the hypothesis that there are previously un-described molecular/biochemical specializations within varanid skeletal muscles. PMID- 27660611 TI - From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine. AB - Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalized medicine, that is the selection of medicines for subgroups of patients so as to maximize drug efficacy and minimize toxicity, is a key goal of twenty-first century healthcare. Currently, most personalized medicine paradigms rely on clinical judgment based on the patient's history, and on the analysis of the patients' genome to predict drug effects i.e., pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as "the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures." The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments. PMID- 27660613 TI - Multiparametric Magnetic Resonance Investigation of Brain Adaptations to 6 Days at 4350 m. AB - OBJECTIVE: Hypoxic exposure in healthy subjects can induce acute mountain sickness including headache, lethargy, cerebral dysfunction, and substantial cerebral structural alterations which, in worst case, can lead to potentially fatal high altitude cerebral edema. Within this context, the relationships between high altitude-induced cerebral edema, changes in cerebral perfusion, increased brain parenchyma volume, increased intracranial pressure, and symptoms remain unclear. METHODS: In 11 subjects before and after 6 days at 4350 m, we performed multiparametric magnetic resonance investigations including anatomical, apparent diffusion coefficient and arterial spin labeling sequences. RESULTS: After the altitude stay, while subjects were asymptomatic, white matter volume (+0.7 +/- 0.4%, p = 0.005), diffusion (+1.7 +/- 1.4%, p = 0.002), and cerebral blood flow (+28 +/- 38%; p = 0.036) were significantly increased while cerebrospinal fluid volume was reduced (-1.4 +/- 1.1%, p = 0.009). Optic nerve sheath diameter (used as an index of increased intracranial pressure) was unchanged from before (5.84 +/- 0.53 mm) to after (5.92 +/- 0.60 mm, p = 0.390) altitude exposure. Correlations were observed between increases in white matter volume and diffusion (rho = 0.81, p = 0.016) and between changes in CSF volume and changes in ONSD s (rho = -0.92, p = 0.006) and symptoms during the altitude stay (rho = -0.67, p = 0.031). CONCLUSIONS: These data demonstrate white matter alterations after several days at high altitude when subjects are asymptomatic that may represent the normal brain response to prolonged high altitude exposure. PMID- 27660614 TI - Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications. AB - Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue (WAT) is an active endocrine organ, with a crucial influence on whole-body homeostasis. WAT dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease, and some cancers. Among the regulators of WAT physiology, the calcium-sensing receptor (CaSR) has arisen as a potential mediator of WAT dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that CaSR activation in the visceral (i.e., unhealthy) WAT is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to CaSR activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in WAT plays a key role in the development of WAT dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that CaSR may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic. PMID- 27660616 TI - The Body That Speaks: Recombining Bodies and Speech Sources in Unscripted Face-to Face Communication. AB - This article examines advances in research methods that enable experimental substitution of the speaking body in unscripted face-to-face communication. A taxonomy of six hybrid social agents is presented by combining three types of bodies (mechanical, virtual, and human) with either an artificial or human speech source. Our contribution is to introduce and explore the significance of two particular hybrids: (1) the cyranoid method that enables humans to converse face to-face through the medium of another person's body, and (2) the echoborg method that enables artificial intelligence to converse face-to-face through the medium of a human body. These two methods are distinct in being able to parse the unique influence of the human body when combined with various speech sources. We also introduce a new framework for conceptualizing the body's role in communication, distinguishing three levels: self's perspective on the body, other's perspective on the body, and self's perspective of other's perspective on the body. Within each level the cyranoid and echoborg methodologies make important research questions tractable. By conceptualizing and synthesizing these methods, we outline a novel paradigm of research on the role of the body in unscripted face to-face communication. PMID- 27660615 TI - Redundancy and Molecular Evolution: The Rapid Induction of Bone Formation by the Mammalian Transforming Growth Factor-beta3 Isoform. AB - The soluble osteogenic molecular signals of the transforming growth factor-beta (TGF-beta) supergene family are the molecular bases of the induction of bone formation and postnatal bone tissue morphogenesis with translation into clinical contexts. The mammalian TGF-beta3 isoform, a pleiotropic member of the family, controls a vast array of biological processes including the induction of bone formation. Recombinant hTGF-beta3 induces substantial bone formation when implanted with either collagenous bone matrices or coral-derived macroporous bioreactors in the rectus abdominis muscle of the non-human primate Papio ursinus. In marked contrast, the three mammalian TGF-betas do not initiate the induction of bone formation in rodents and lagomorphs. The induction of bone by hTGF-beta3/preloaded bioreactors is orchestrated by inducing fibrin-fibronectin rings that structurally organize tissue patterning and morphogenesis within the macroporous spaces. Induced advancing extracellular matrix rings provide the structural anchorage for hyper chromatic cells, interpreted as differentiating osteoblasts re-programmed by hTGF-beta3 from invading myoblastic and/or pericytic differentiated cells. Runx2 and Osteocalcin expression are significantly up regulated correlating to multiple invading cells differentiating into the osteoblastic phenotype. Bioreactors pre-loaded with recombinant human Noggin (hNoggin), a BMPs antagonist, show down-regulation of BMP-2 and other profiled osteogenic proteins' genes resulting in minimal bone formation. Coral-derived macroporous constructs preloaded with binary applications of hTGF-beta3 and hNoggin also show down-regulation of BMP-2 with the induction of limited bone formation. The induction of bone formation by hTGF-beta3 is via the BMPs pathway and it is thus blocked by hNoggin. Our systematic studies in P. ursinus with translational hTGF-beta3 in large cranio-mandibulo-facial defects in humans are now requesting the re-evaluation of "Bone: formation by autoinduction" in primate models including humans. PMID- 27660617 TI - Why Does the "Sinner" Act Prosocially? The Mediating Role of Guilt and the Moderating Role of Moral Identity in Motivating Moral Cleansing. AB - Numerous studies have found that people tend to commit prosocial acts subsequent to previous immoral acts, as a response to the latter. This phenomenon is called moral cleansing or moral compensation. However, the specific mechanism how previous immoral acts motivate moral compensatory behaviors is still not fully understood. This study aimed to examine the roles of guilt and moral identity in the relation between previous immoral acts and subsequent prosocial behaviors to clarify the mechanism. Based on the extant research, the current study proposed a moderated mediation model to illustrate the process of moral cleansing. Specifically, a previous immoral act motivates guilt, which further leads to subsequent prosocial behaviors, while moral identity facilitates this process. The participants were primed by a recalling task (immoral act vs. a neutral event). The results support the hypothesized model and provide a framework that explains moral cleansing by integrating the roles of guilt and moral identity. These findings highlight the dynamic nature of people's morality with regard to how people adapt moral behaviors to protect their moral self-image. PMID- 27660618 TI - Specific Barriers and Drivers in Different Stages of Decision-Making about Energy Efficiency Upgrades in Private Homes. AB - Energy efficiency upgrades of privately owned homes like adding to the insulation layers in the walls, roof or floor, or replacing windows with more efficiently insulated versions can contribute significantly to reducing the energy impact of the building sector and thus also the CO2 footprint of a household. However, even in countries like Norway that have a rather high rate of renovation, energy upgrades are not always integrated into such a refurbishment project. This study tests which structural and internal psychological barriers hinder and which drivers foster decision-making to implement such measures, once a renovation project is planned. With a theoretical background in stage-based models of decision-making 24 barriers and drivers were tested for their specific effect in the stages of decision-making. The four stages of decision-making assumed in this study were (1) "not being in a decision mode," (2) "deciding what to do," (3) "deciding how to do it," and (4) "planning implementation." Based on an online survey of 3787 Norwegian households, it was found that the most important barriers toward deciding to implement energy efficiency upgrades were not owning the dwelling and feeling the right time had not come yet. The most important drivers of starting to decide were higher expected comfort levels, better expected living conditions, and an expected reduction of energy costs. For the transition from deciding what to do to how to do it, not managing to make a decision and feeling the right point in time has not come yet were the strongest barriers, easily accessible information and an expected reduction of energy costs were the most important drivers. The final transition from deciding how to do the upgrades to planning implementation was driven by expecting a payoff within a reasonable time frame and higher expected comfort levels; the most important barriers were time demands for supervising contractors and-again-a feeling that the right point in time has not come yet. Implications for policy-making and marketing are discussed. PMID- 27660619 TI - A New Measure of Reading Habit: Going Beyond Behavioral Frequency. AB - Reading habit is considered an important construct in reading research as it serves as a significant predictor of reading achievement. However, there is still no consensus on how to best measure reading habit. In recent research, it has mostly been measured as behavioral frequency; this approach neglects the fact that repeated behavior does not cover the broad content of habitual behavior-such as automaticity and the expression of one's identity. In this study, we aimed to adapt a 10-item scale on the basis of the Self-Report Habit Index by Verplanken and Orbell (2003) that is comprehensive but still economical for measuring reading habit. It was tested by drawing on a sample of N = 1,418 upper secondary school students. The scale showed good psychometric properties and the internal and external validity was supported. Moreover, the scale predicted reading achievement and decoding speed over and above reading frequency. The implications of an elaborated but still economical way of measuring reading habit are discussed giving new impetus on research on reading habit, challenging conventional approaches of traditional measures. PMID- 27660620 TI - From Sweeping to the Caress: Similarities and Discrepancies between Human and Non Human Primates' Pleasant Touch. AB - Affective touch plays a key role in affiliative behavior, offering a mechanism for the formation and maintenance of social bonds among conspecifics, both in humans and non-human primates. Furthermore, it has been speculated that the CT fiber system is a specific coding channel for affiliative touch that occurs during skin-to-skin interactions with conspecifics. In humans, this touch is commonly referred to as the caress, and its correlation with the CT fiber system has been widely demonstrated. It has been hypothesized that the sweeping touch that occurs during grooming in non-human primates may modulate the CT fibers, with recent preliminary studies on rhesus monkeys supporting this hypothesis. The present mini-review proposes a comparison between the pleasant touch, caress and sweeping of humans and non-human primates, respectively. The currently available data was therefore reviewed regarding (i) the correlation between pleasant touch and CT fibers both in humans and non-human primates, (ii) the autonomic effects, (iii) the encoding at the central nervous system, (iv) the development from early life to adulthood, and (v) the potential applications of pleasant touch in the daily lives of both humans and non-human primates. Moreover, by considering both the similarities and discrepancies between the human caress and non-human primate sweeping, a possible evolutionary mechanism can be proposed that has developed from sweeping as a utilitarian action with affiliative meaning among monkeys, to the caress as a purely affective gesture associated with humans. PMID- 27660622 TI - Leisingera sp. JC1, a Bacterial Isolate from Hawaiian Bobtail Squid Eggs, Produces Indigoidine and Differentially Inhibits Vibrios. AB - Female members of many cephalopod species house a bacterial consortium in the accessory nidamental gland (ANG), part of the reproductive system. These bacteria are deposited into eggs that are then laid in the environment where they must develop unprotected from predation, pathogens, and fouling. In this study, we characterized the genome and secondary metabolite production of Leisingera sp. JC1, a member of the roseobacter clade (Rhodobacteraceae) of Alphaproteobacteria isolated from the jelly coat of eggs from the Hawaiian bobtail squid, Euprymna scolopes. Whole genome sequencing and MLSA analysis revealed that Leisingera sp. JC1 falls within a group of roseobacters associated with squid ANGs. Genome and biochemical analyses revealed the potential for and production of a number of secondary metabolites, including siderophores and acyl-homoserine lactones involved with quorum sensing. The complete biosynthetic gene cluster for the pigment indigoidine was detected in the genome and mass spectrometry confirmed the production of this compound. Furthermore, we investigated the production of indigoidine under co-culture conditions with Vibrio fischeri, the light organ symbiont of E. scolopes, and with other vibrios. Finally, both Leisingera sp. JC1 and secondary metabolite extracts of this strain had differential antimicrobial activity against a number of marine vibrios, suggesting that Leisingera sp. JC1 may play a role in host defense against other marine bacteria either in the eggs and/or ANG. These data also suggest that indigoidine may be partially, but not wholly, responsible for the antimicrobial activity of this squid-associated bacterium. PMID- 27660623 TI - More Is Better: Selecting for Broad Host Range Bacteriophages. AB - Bacteriophages are viruses that infect bacteria. In this perspective, we discuss several aspects of a characteristic feature of bacteriophages, their host range. Each phage has its own particular host range, the range of bacteria that it can infect. While some phages can only infect one or a few bacterial strains, other phages can infect many species or even bacteria from different genera. Different methods for determining host range may give different results, reflecting the multiple mechanisms bacteria have to resist phage infection and reflecting the different steps of infection each method depends on. This makes defining host range difficult. Another difficulty in describing host range arises from the inconsistent use of the words "narrow" and especially "broad" when describing the breadth of the host range. Nearly all bacteriophages have been isolated using a single host strain of bacteria. While this procedure is fairly standard, it may more likely produce narrow rather than broad host range phage. Our results and those of others suggest that using multiple host strains during isolation can more reliably produce broader host range phages. This challenges the common belief that most bacteriophages have a narrow host range. We highlight the implications of this for several areas that are affected by host range including horizontal gene transfer and phage therapy. PMID- 27660625 TI - Bacteriophage T4 Infection of Stationary Phase E. coli: Life after Log from a Phage Perspective. AB - Virtually all studies of phage infections investigate bacteria growing exponentially in rich media. In nature, however, phages largely encounter non growing cells. Bacteria entering stationary phase often activate well-studied stress defense mechanisms that drastically alter the cell, facilitating its long term survival. An understanding of phage-host interactions in such conditions is of major importance from both an ecological and therapeutic standpoint. Here, we show that bacteriophage T4 can efficiently bind to, infect and kill E. coli in stationary phase, both in the presence and absence of a functional stationary phase sigma factor, and explore the response of T4-infected stationary phase cells to the addition of fresh nutrients 5 or 24 h after that infection. An unexpected new mode of response has been identified. "Hibernation" mode is a persistent but reversible dormant state in which the infected cells make at least some phage enzymes, but halt phage development until appropriate nutrients become available before producing phage particles. Our evidence indicates that the block in hibernation mode occurs after the middle-mode stage of phage development; host DNA breakdown and the incorporation of the released nucleotides into phage DNA indicate that the enzymes of the nucleotide synthesizing complex, under middle mode control, have been made and assembled into a functional state. Once fresh glucose and amino acids become available, the standard lytic infection process rapidly resumes and concentrations of up to 10(11) progeny phage (an average of about 40 phage per initially present cell) are produced. All evidence is consistent with the hibernation-mode control point lying between middle mode and late mode T4 gene expression. We have also observed a "scavenger" response, where the infecting phage takes advantage of whatever few nutrients are available to produce small quantities of progeny within 2 to 5 h after infection. The scavenger response seems able to produce no more than an average of one phage per originally available cell, and few if any further progeny are produced by cells in this mode even if fresh nutrients are made available later. PMID- 27660626 TI - Editorial: Control of Pestivirus Infections in the Management of Wildlife Populations. PMID- 27660624 TI - The Willow Microbiome Is Influenced by Soil Petroleum-Hydrocarbon Concentration with Plant Compartment-Specific Effects. AB - The interaction between plants and microorganisms, which is the driving force behind the decontamination of petroleum hydrocarbon (PHC) contamination in phytoremediation technology, is poorly understood. Here, we aimed at characterizing the variations between plant compartments in the microbiome of two willow cultivars growing in contaminated soils. A field experiment was set-up at a former petrochemical plant in Canada and after two growing seasons, bulk soil, rhizosphere soil, roots, and stems samples of two willow cultivars (Salix purpurea cv. FishCreek, and Salix miyabeana cv. SX67) growing at three PHC contamination concentrations were taken. DNA was extracted and bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) regions were amplified and sequenced using an Ion Torrent Personal Genome Machine (PGM). Following multivariate statistical analyses, the level of PHC-contamination appeared as the primary factor influencing the willow microbiome with compartment-specific effects, with significant differences between the responses of bacterial, and fungal communities. Increasing PHC contamination levels resulted in shifts in the microbiome composition, favoring putative hydrocarbon degraders, and microorganisms previously reported as associated with plant health. These shifts were less drastic in the rhizosphere, root, and stem tissues as compared to bulk soil, probably because the willows provided a more controlled environment, and thus, protected microbial communities against increasing contamination levels. Insights from this study will help to devise optimal plant microbiomes for increasing the efficiency of phytoremediation technology. PMID- 27660627 TI - Editorial: Actinobacteria in Special and Extreme Habitats: Diversity, Function Roles, and Environmental Adaptations. PMID- 27660621 TI - Predictors of Cognitive Decline in Older Adult Type 2 Diabetes from the Veterans Affairs Diabetes Trial. AB - AIMS: Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial. METHODS: A battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5. Thirty-seven risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses. RESULTS: The mean age-adjusted DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized INT glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (BP; beta = 0.028; P = 0.002), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age adjusted TMT-B suggesting a role for both higher systolic and lower diastolic BPs. Baseline thiazide diuretic use (beta = -0.549; P = 0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post baseline systolic BP-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride-lowering (P = 0.045) and decline in digit symbol substitution task performance. CONCLUSION: A 5-year period of randomized INT glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic BPs as well as plasma triglycerides appeared as modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes. PMID- 27660628 TI - Shortening of the Lactobacillus paracasei subsp. paracasei BGNJ1-64 AggLb Protein Switches Its Activity from Auto-aggregation to Biofilm Formation. AB - AggLb is the largest (318.6 kDa) aggregation-promoting protein of Lactobacillus paracasei subsp. paracasei BGNJ1-64 responsible for forming large cell aggregates, which causes auto-aggregation, collagen binding and pathogen exclusion in vitro. It contains an N-terminus leader peptide, followed by six successive collagen binding domains, 20 successive repeats (CnaB-like domains) and an LPXTG sorting signal at the C-terminus for cell wall anchoring. Experimental information about the roles of the domains of AggLb is currently unknown. To define the domain that confers cell aggregation and the key domains for interactions of specific affinity between AggLb and components of the extracellular matrix, we constructed a series of variants of the aggLb gene and expressed them in Lactococcus lactis subsp. lactis BGKP1-20 using a lactococcal promoter. All of the variants contained a leader peptide, an inter collagen binding-CnaB domain region (used to raise an anti-AggLb antibody), an anchor domain and a different number of collagen binding and CnaB-like domains. The role of the collagen binding repeats of the N-terminus in auto-aggregation and binding to collagen and fibronectin was confirmed. Deletion of the collagen binding repeats II, III, and IV resulted in a loss of the strong auto-aggregation, collagen and fibronectin binding abilities whereas the biofilm formation capability was increased. The strong auto-aggregation, collagen and fibronectin binding abilities of AggLb were negatively correlated to biofilm formation. PMID- 27660629 TI - Corrigendum: Whole-Transcriptome Analysis of Verocytotoxigenic Escherichia coli O157:H7 (Sakai) Suggests Plant-Species-Specific Metabolic Responses on Exposure to Spinach and Lettuce Extracts. AB - [This corrects the article on p. 1088 in vol. 7, PMID: 27462311.]. PMID- 27660630 TI - Commentary: Arnica Montana Effects on Gene Expression in a Human Macrophage Cell Line: Evaluation by Quantitative Real-Time PCR. PMID- 27660632 TI - Genome-Wide SNP Linkage Mapping and QTL Analysis for Fiber Quality and Yield Traits in the Upland Cotton Recombinant Inbred Lines Population. AB - It is of significance to discover genes related to fiber quality and yield traits and tightly linked markers for marker-assisted selection (MAS) in cotton breeding. In this study, 188 F8 recombinant inbred lines (RILs), derived from a intraspecific cross between HS46 and MARCABUCAG8US-1-88 were genotyped by the cotton 63K single nucleotide polymorphism (SNP) assay. Field trials were conducted in Sanya, Hainan Province, during the 2014-2015 cropping seasons under standard conditions. Results revealed significant differences (P < 0.05) among RILs, environments and replications for fiber quality and yield traits. Broad sense heritabilities of all traits including fiber length, fiber uniformity, micronaire, fiber elongation, fiber strength, boll weight, and lint percentage ranged from 0.26 to 0.66. A 1784.28 cM (centimorgans) linkage map, harboring 2618 polymorphic SNP markers, was constructed, which had 0.68 cM per marker density. Seventy-one quantitative trait locus (QTLs) for fiber quality and yield traits were detected on 21 chromosomes, explaining 4.70~32.28% phenotypic variance, in which 16 were identified as stable QTLs across two environments. Meanwhile, 12 certain regions were investigated to be involved in the control of one (hotspot) or more (cluster) traits, mainly focused on Chr05, Chr09, Chr10, Chr14, Chr19, and Chr20. Nineteen pairs of epistatic QTLs (e-QTLs) were identified, of which two pairs involved in two additive QTLs. These additive QTLs, e-QTLs, and QTL clusters were tightly linked to SNP markers, which may serve as target regions for map-based cloning, gene discovery, and MAS in cotton breeding. PMID- 27660633 TI - Nickel Availability in Soil as Influenced by Liming and Its Role in Soybean Nitrogen Metabolism. AB - Nickel (Ni) availability in soil varies as a function of pH. Plants require Ni in small quantities for normal development, especially in legumes due its role in nitrogen (N) metabolism. This study investigated the effect of soil base saturation, and Ni amendments on Ni uptake, N accumulation in the leaves and grains, as well as to evaluate organic acids changes in soybean. In addition, two N assimilation enzymes were assayed: nitrate reductase (NR) and Ni-dependent urease. Soybean plants inoculated with Bradyrhizobium japonicum were cultivated in soil-filled pots under two base-cation saturation (BCS) ratios (50 and 70%) and five Ni rates - 0.0; 0.1; 0.5; 1.0; and 10.0 mg dm(-3) Ni. At flowering (R1 developmental stage), plants for each condition were evaluated for organic acids (oxalic, malonic, succinic, malic, tartaric, fumaric, oxaloacetic, citric and lactic) levels as well as the activities of urease and NR. At the end of the growth period (R7 developmental stage - grain maturity), grain N and Ni accumulations were determined. The available soil-Ni in rhizosphere extracted by DTPA increased with Ni rates, notably in BCS50. The highest concentrations of organic acid and N occurred in BCS70 and 0.5 mg dm(-3) of Ni. There were no significant differences for urease activity taken on plants grown at BSC50 for Ni rates, except for the control treatment, while plants cultivated at soil BCS70 increased the urease activity up to 0.5 mg dm(-3) of Ni. In addition, the highest values for urease activities were reached from the 0.5 mg dm(-3) of Ni rate for both BCS treatments. The NR activity was not affected by any treatment indicating good biological nitrogen fixation (BNF) for all plants. The reddish color of the nodules increased with Ni rates in both BCS50 and 70, also confirms the good BNF due to Ni availability. The optimal development of soybean occurs in BCS70, but requires an extra Ni supply for the production of organic acids and for increased N-shoot and grain accumulation. PMID- 27660635 TI - Stochastic convex sparse principal component analysis. AB - Principal component analysis (PCA) is a dimensionality reduction and data analysis tool commonly used in many areas. The main idea of PCA is to represent high-dimensional data with a few representative components that capture most of the variance present in the data. However, there is an obvious disadvantage of traditional PCA when it is applied to analyze data where interpretability is important. In applications, where the features have some physical meanings, we lose the ability to interpret the principal components extracted by conventional PCA because each principal component is a linear combination of all the original features. For this reason, sparse PCA has been proposed to improve the interpretability of traditional PCA by introducing sparsity to the loading vectors of principal components. The sparse PCA can be formulated as an l1 regularized optimization problem, which can be solved by proximal gradient methods. However, these methods do not scale well because computation of the exact gradient is generally required at each iteration. Stochastic gradient framework addresses this challenge by computing an expected gradient at each iteration. Nevertheless, stochastic approaches typically have low convergence rates due to the high variance. In this paper, we propose a convex sparse principal component analysis (Cvx-SPCA), which leverages a proximal variance reduced stochastic scheme to achieve a geometric convergence rate. We further show that the convergence analysis can be significantly simplified by using a weak condition which allows a broader class of objectives to be applied. The efficiency and effectiveness of the proposed method are demonstrated on a large scale electronic medical record cohort. PMID- 27660631 TI - Role of Proteomics in Crop Stress Tolerance. AB - Plants often experience various biotic and abiotic stresses during their life cycle. The abiotic stresses include mainly drought, salt, temperature (low/high), flooding and nutritional deficiency/excess which hamper crop growth and yield to a great extent. In view of a projection 50% of the crop loss is attributable to abiotic stresses. However, abiotic stresses cause a myriad of changes in physiological, molecular and biochemical processes operating in plants. It is now widely reported that several proteins respond to these stresses at pre- and post transcriptional and translational levels. By knowing the role of these stress inducible proteins, it would be easy to comprehensively expound the processes of stress tolerance in plants. The proteomics study offers a new approach to discover proteins and pathways associated with crop physiological and stress responses. Thus, studying the plants at proteomic levels could help understand the pathways involved in stress tolerance. Furthermore, improving the understanding of the identified key metabolic proteins involved in tolerance can be implemented into biotechnological applications, regarding recombinant/transgenic formation. Additionally, the investigation of identified metabolic processes ultimately supports the development of antistress strategies. In this review, we discussed the role of proteomics in crop stress tolerance. We also discussed different abiotic stresses and their effects on plants, particularly with reference to stress-induced expression of proteins, and how proteomics could act as vital biotechnological tools for improving stress tolerance in plants. PMID- 27660634 TI - Tityus serrulatus envenoming in non-obese diabetic mice: a risk factor for severity. AB - BACKGROUND: In Brazil, accidents with venomous animals are considered a public health problem. Tityus serrulatus (Ts), popularly known as the yellow scorpion, is most frequently responsible for the severe accidents in the country. Ts envenoming can cause several signs and symptoms classified according to their clinical manifestations as mild, moderate or severe. Furthermore, the victims usually present biochemical alterations, including hyperglycemia. Nevertheless, Ts envenoming and its induced hyperglycemia were never studied or documented in a patient with diabetes mellitus (DM). Therefore, this is the first study to evaluate the glycemia during Ts envenoming using a diabetic animal model (NOD, non-obese diabetic). METHODS: Female mice (BALB/c or NOD) were challenged with a non-lethal dose of Ts venom. Blood glucose level was measured (tail blood using a glucose meter) over a 24-h period. The total glycosylated hemoglobin (HbA1c) levels were measured 30 days after Ts venom injection. Moreover, the insulin levels were analyzed at the glycemia peak. RESULTS: The results demonstrated that the envenomed NOD animals presented a significant increase of glycemia, glycosylated hemoglobin (HbA1c) and insulin levels compared to the envenomed BALB/c control group, corroborating that DM victims present great risk of developing severe envenoming. Moreover, the envenomed NOD animals presented highest risk of death and sequelae. CONCLUSIONS: This study demonstrated that the diabetic victims stung by Ts scorpion should be always considered a risk group for scorpion envenoming severity. PMID- 27660636 TI - Automated Fovea Detection in Spectral Domain Optical Coherence Tomography Scans of Exudative Macular Disease. AB - In macular spectral domain optical coherence tomography (SD-OCT) volumes, detection of the foveal center is required for accurate and reproducible follow up studies, structure function correlation, and measurement grid positioning. However, disease can cause severe obscuring or deformation of the fovea, thus presenting a major challenge in automated detection. We propose a fully automated fovea detection algorithm to extract the fovea position in SD-OCT volumes of eyes with exudative maculopathy. The fovea is classified into 3 main appearances to both specify the detection algorithm used and reduce computational complexity. Based on foveal type classification, the fovea position is computed based on retinal nerve fiber layer thickness. Mean absolute distance between system and clinical expert annotated fovea positions from a dataset comprised of 240 SD-OCT volumes was 162.3 um in cystoid macular edema and 262 um in nAMD. The presented method has cross-vendor functionality, while demonstrating accurate and reliable performance close to typical expert interobserver agreement. The automatically detected fovea positions may be used as landmarks for intra- and cross-patient registration and to create a joint reference frame for extraction of spatiotemporal features in "big data." Furthermore, reliable analyses of retinal thickness, as well as retinal structure function correlation, may be facilitated. PMID- 27660637 TI - Continuing Medical Education via Telemedicine and Sustainable Improvements to Health. AB - Background. This research aims to investigate the quantitative relationship between telemedicine and online continuing medical education (CME) and to find the optimal CME lectures to be delivered via telemedicine to improve the population's health status. Objective. This study examines the following: (1) What factors foster learning processes in CME via telemedicine? (2) What is the possible role of online CME in health improvement? And (3) How optimal learning processes can be integrated with various health services? Methods. By applying telemedicine experiences in Taiwan over the period 1995-2004, this study uses panel data and the method of ordinary least squares to embed an adequate set of phenomena affecting the provision of online CME lectures versus health status. Results. Analytical results find that a nonlinear online CME-health nexus exists. Increases in the provision of online CME lectures are associated with health improvements. However, after the optimum has been reached, greater provision of online CME lectures may be associated with decreasing population health. Conclusion. Health attainment could be partially viewed as being determined by the achievement of the appropriately providing online CME lectures. This study has evaluated the population's health outcomes and responded to the currently inadequate provision of online CME lectures via telemedicine. PMID- 27660638 TI - Data Acquisition System for In Situ Monitoring of Chemoelectrical Potential in Living Plant Fuel Cells. AB - Photosynthesis process in plants generates numerous sources of bioenergy. However, only a small fraction is readily exploited for electrical energy. The impact of environmental factors is one of the significant physiological influences on the electrical potential of the plants. Hence, we developed a data acquisition (DAQ) system for instantaneous monitoring of electrical potential in plants and Aloe vera was used as a plant sample. The static response characterization, capability index (P/T), and Pearson's coefficient of correlation procedures were applied to assess the reliability of the obtained data. This developed system offers the capability of in situ monitoring and detecting gradual changes in the electrical potential of plants up to a correlational strength of greater than 0.7. Interpretation of the electrical signal mechanisms in the Aloe vera plant and the optimization of the electricity can be achieved through the application of this monitoring system. This system, therefore, can serve as a tool to measure and analyze the electrical signals in plants at different conditions. PMID- 27660639 TI - Local perceptions as a guide for the sustainable management of natural resources: empirical evidence from a small-scale society in Bolivian Amazonia. AB - Research on natural resource management suggests that local perceptions form the basis upon which many small-scale societies monitor availability and change in the stock of common-pool natural resources. In contrast, this literature debates whether local perceptions can be effective in guiding the sustainable management of natural resources. With empirical evidence on this matter still highly limited, this work explores the role of local perceptions as drivers of harvesting and management behavior in a small-scale society in Bolivian Amazonia. We conducted structured interviews to capture local perceptions of availability and change in the stock of thatch palm (Geonoma deversa) amongst the Tsimane', an indigenous society of foragers-horticulturalists (n = 296 adults in 13 villages). We analyzed whether perceptions of availability match estimates of abundance obtained from ecological data and whether differences in perception help to explain harvesting behavior and local management of thatch palm. Perceptions of availability of G. deversa are highly contingent upon the social, economic and cultural conditions within which the Tsimane' have experienced changes in the availability of the resource, thus giving a better reflection of the historical, rather than of the ecological, dimensions of the changes undergone. While local perceptions might fall short in precision when scrutinized from an ecological standpoint, their importance in informing sustainable management should not be underestimated. Our findings show that most of the harvesting and management actions that the Tsimane' undertake are, at least partially, shaped by their local perceptions. This paper contributes to the broader literature on natural resource management by providing empirical evidence of the critical role of local perceptions in promoting collective responses for the sustainable management of natural resources. PMID- 27660640 TI - A novel combination of an IgE mediated adult onset food allergy and a suspected mast cell activation syndrome presenting as anaphylaxis. AB - BACKGROUND: Adult onset food allergy is a rare, but increasingly recognized phenomenon. Mast cell activation syndromes present an ongoing diagnostic and classification challenge. The combination of the two has been rarely described in the literature. CASE PRESENTATION: We present a case of a new onset, IgE mediated food allergy in combination with a mast cell activation syndrome in an elderly patient not known to have a history of atopy. He presented to a hospital with a first presentation of anaphylaxis manifesting profound hypotension following consumption of a stew consisting of fish and shellfish. He had a persistently elevated serum tryptase and demonstrated evidence of high titre serum specific IgE to shellfish. He responded well to histaminergic blockade. CONCLUSIONS: Given that mast cell activation syndromes pose an increased risk for recurrent, severe anaphylaxis and that secondary causes of mast cell activation syndromes are more prevalent with aging, this case highlights the importance of considering this entity when evaluating an elderly patient with a first presentation of anaphylaxis. PMID- 27660642 TI - Effects of mindfulness-based cognitive therapy on mental disorders: a systematic review and meta-analysis of randomised controlled trials. AB - OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) is a programme developed to prevent depression relapse, but has been applied for other disorders. Our objective was to systematically review and meta-analyse the evidence on the effectiveness and safety of MBCT for the treatment of mental disorders. METHODS: Searches were completed in CENTRAL, MEDLINE, EMBASE, LILACS, PsychINFO, and PsycEXTRA in March 2011 using a search strategy with the terms 'mindfulness-based cognitive therapy', 'mindfulness', and 'randomised controlled trials' without time restrictions. Selection criteria of having a randomised controlled trial design, including patients diagnosed with mental disorders, using MBCT according to the authors who developed MBCT and providing outcomes that included changes in mental health were used to assess 608 reports. Two reviewers applied the pre determined selection criteria and extracted the data into structured tables. Meta analyses and sensitivity analyses were completed. RESULTS: Eleven studies were included. Most of them evaluated depression and compared additive MBCT against usual treatment. After 1 year of follow-up MBCT reduced the rate of relapse in patients with three or more previous episodes of depression by 40% (5 studies, relative risk [95% confidence interval]: 0.61 [0.48, 0.79]). Other meta-analysed outcomes were depression and anxiety, both with significant results but unstable in sensitivity analyses. Methodological quality of the reports was moderate. CONCLUSION: Based on this review and meta-analyses, MBCT is an effective intervention for patients with three or more previous episodes of major depression. PMID- 27660641 TI - The bear circadian clock doesn't 'sleep' during winter dormancy. AB - BACKGROUND: Most biological functions are synchronized to the environmental light:dark cycle via a circadian timekeeping system. Bears exhibit shallow torpor combined with metabolic suppression during winter dormancy. We sought to confirm that free-running circadian rhythms of body temperature (Tb) and activity were expressed in torpid grizzly (brown) bears and that they were functionally responsive to environmental light. We also measured activity and ambient light exposures in denning wild bears to determine if rhythms were evident and what the photic conditions of their natural dens were. Lastly, we used cultured skin fibroblasts obtained from captive torpid bears to assess molecular clock operation in peripheral tissues. Circadian parameters were estimated using robust wavelet transforms and maximum entropy spectral analyses. RESULTS: Captive grizzly bears housed in constant darkness during winter dormancy expressed circadian rhythms of activity and Tb. The rhythm period of juvenile bears was significantly shorter than that of adult bears. However, the period of activity rhythms in adult captive bears was virtually identical to that of adult wild denning bears as was the strength of the activity rhythms. Similar to what has been found in other mammals, a single light exposure during the bear's active period delayed subsequent activity onsets whereas these were advanced when light was applied during the bear's inactive period. Lastly, in vitro studies confirmed the expression of molecular circadian rhythms with a period comparable to the bear's own behavioral rhythms. CONCLUSIONS: Based on these findings we conclude that the circadian system is functional in torpid bears and their peripheral tissues even when housed in constant darkness, is responsive to phase-shifting effects of light, and therefore, is a normal facet of torpid bear physiology. PMID- 27660643 TI - Total and respirable dust exposures among carpenters and demolition workers during indoor work in Denmark. AB - BACKGROUND: Within the construction industry the risk of lung disorders depends on the specific professions probably due to variations in the levels of dust exposure, and with dust levels depending on the work task and job function. We do not know the extent of exposure in the different professions or the variation between the different work tasks. The purpose of this study was therefore to assess if there were differences in dust exposure between carpenters and demolition workers who were expected to have low and high dust exposure, respectively. METHODS: Through interviews of key persons in the construction industry the most common work tasks were selected, and the concentration of dust during these tasks (indoors) were measured by personal sampling varying between 4 and 6 h of a working day. In total 38 measurements of total dust, and 25 of respirable dust on seven different work tasks were carried out for carpenters and 20 measurements of total dust, 11 of respirable dust and 11 of respirable crystalline silica dust on four different works tasks for demolition workers. Dust measurements were tested for differences using linear regression, t-test and one-way ANOVA. RESULTS: For carpenters the geometric mean for all the measurements of total dust was 1.26 mg/m(3) (geometric standard deviation 2.90) and the respirable dust was 0.27 mg/m(3) (geometric standard deviation 2.13). For demolition workers the geometric mean of total dust for all the measurements was 22.3 mg/m(3) (geometric standard deviation 11.6) and the respirable dust was 1.06 mg/m(3) (geometric standard deviation 5.64). The mean difference between total dust for demolition workers and carpenters was 11.4 (95 % confidence interval 3.46-37.1) mg/m(3). The mean difference between respirable dust for demolition workers and carpenters was 3.90 (95 % confidence interval 1.13-13.5) mg/m(3). Dust exposure varied depending on work task for both professions. The dustiest work occurred during demolition, especially when it was done manually. Only few workers used personal respiratory protection and only while performing the dustiest work. CONCLUSIONS: This study confirmed that the exposure to dust and especially total dust was much higher for demolition workers compared to carpenters. TRIAL REGISTRATION: (ISRCTN registry): The study is not a clinical trial and are thus not registered. PMID- 27660644 TI - Prevalence and associated factors of non-exclusive breastfeeding of infants during the first six months in rural area of Sorro District, Southern Ethiopia: a cross-sectional study. AB - BACKGROUND: Despite the importance of exclusive breastfeeding, a wide number of mothers practice non-exclusive breastfeeding in Ethiopia. Therefore, this study aimed to identify prevalence and factors associated with non-exclusive breastfeeding in rural area of Sorro District in Southern Ethiopia. METHODS: A community based cross-sectional study was undertaken. The study population consisted of all mothers with infants aged of 0-5 months living in the randomly selected kebeles (lowest administrative unit) in the rural area of Sorro District. The study was conducted on 602 mothers with infants selected by using systematic sampling method from 12 August to 23 August 2015. Both bivariate and multivariable logistic regression analysis were used to assess the association between the study variables and to control possible confounding. RESULTS: The prevalence of non-exclusive breastfeeding in infants under 6 months was 49.4 %. Being currently unmarried [AOR (95 % CI) = 3.85 (1.44, 10.27)], index infant's age being within 2-3 months [AOR (95 % CI) = 3.63 (2.06, 6.36)] and 4-5 months [AOR (95 % CI) =10.29 (5.60, 18.92)] compared to infant age 0-1 month, initiation of breastfeeding after 1 h of birth [AOR (95 % CI) = 2.11 (1.37, 3.24)], no antenatal care visit during their last pregnancy [AOR (95 % CI) =2.60 (1.64, 4.10)] and no postnatal care visit after delivery [AOR (95 % CI) = 1.90 (1.19, 3.04)] were significantly associated with non-exclusive breastfeeding. CONCLUSION: In this study a large proportion of mothers with infants under 6 months of age were practicing non-exclusive breastfeeding which is one of the major risks for infant and child morbidity and mortality. Taking measures on identified associated factors with non-exclusive breastfeeding was recommended to improve the status of exclusive breastfeeding in the study area. PMID- 27660645 TI - An Active Learning Classifier for Further Reducing Diabetic Retinopathy Screening System Cost. AB - Diabetic retinopathy (DR) screening system raises a financial problem. For further reducing DR screening cost, an active learning classifier is proposed in this paper. Our approach identifies retinal images based on features extracted by anatomical part recognition and lesion detection algorithms. Kernel extreme learning machine (KELM) is a rapid classifier for solving classification problems in high dimensional space. Both active learning and ensemble technique elevate performance of KELM when using small training dataset. The committee only proposes necessary manual work to doctor for saving cost. On the publicly available Messidor database, our classifier is trained with 20%-35% of labeled retinal images and comparative classifiers are trained with 80% of labeled retinal images. Results show that our classifier can achieve better classification accuracy than Classification and Regression Tree, radial basis function SVM, Multilayer Perceptron SVM, Linear SVM, and K Nearest Neighbor. Empirical experiments suggest that our active learning classifier is efficient for further reducing DR screening cost. PMID- 27660646 TI - Dynamic Characteristics of Mechanical Ventilation System of Double Lungs with Bi Level Positive Airway Pressure Model. AB - In recent studies on the dynamic characteristics of ventilation system, it was considered that human had only one lung, and the coupling effect of double lungs on the air flow can not be illustrated, which has been in regard to be vital to life support of patients. In this article, to illustrate coupling effect of double lungs on flow dynamics of mechanical ventilation system, a mathematical model of a mechanical ventilation system, which consists of double lungs and a bi level positive airway pressure (BIPAP) controlled ventilator, was proposed. To verify the mathematical model, a prototype of BIPAP system with a double-lung simulators and a BIPAP ventilator was set up for experimental study. Lastly, the study on the influences of key parameters of BIPAP system on dynamic characteristics was carried out. The study can be referred to in the development of research on BIPAP ventilation treatment and real respiratory diagnostics. PMID- 27660647 TI - A Comparison between Cure Model and Recursive Partitioning: A Retrospective Cohort Study of Iranian Female with Breast Cancer. AB - Background. Breast cancer which is the most common cause of women cancer death has an increasing incidence and mortality rates in Iran. A proper modeling would correctly detect the factors' effect on breast cancer, which may be the basis of health care planning. Therefore, this study aimed to practically develop two recently introduced statistical models in order to compare them as the survival prediction tools for breast cancer patients. Materials and Methods. For this retrospective cohort study, the 18-year follow-up information of 539 breast cancer patients was analyzed by "Parametric Mixture Cure Model" and "Model-Based Recursive Partitioning." Furthermore, a simulation study was carried out to compare the performance of mentioned models for different situations. Results. "Model-Based Recursive Partitioning" was able to present a better description of dataset and provided a fine separation of individuals with different risk levels. Additionally the results of simulation study confirmed the superiority of this recursive partitioning for nonlinear model structures. Conclusion. "Model-Based Recursive Partitioning" seems to be a potential instrument for processing complex mixture cure models. Therefore, applying this model is recommended for long-term survival patients. PMID- 27660648 TI - Endoleak Assessment Using Computational Fluid Dynamics and Image Processing Methods in Stented Abdominal Aortic Aneurysm Models. AB - Endovascular aortic aneurysm repair (EVAR) is a predominant surgical procedure to reduce the risk of aneurysm rupture in abdominal aortic aneurysm (AAA) patients. Endoleak formation, which eventually requires additional surgical reoperation, is a major EVAR complication. Understanding the etiology and evolution of endoleak from the hemodynamic perspective is crucial to advancing the current posttreatments for AAA patients who underwent EVAR. Therefore, a comprehensive flow assessment was performed to investigate the relationship between endoleak and its surrounding pathological flow fields through computational fluid dynamics and image processing. Six patient-specific models were reconstructed, and the associated hemodynamics in these models was quantified three-dimensionally to calculate wall stress. To provide a high degree of clinical relevance, the mechanical stress distribution calculated from the models was compared with the endoleak positions identified from the computed tomography images of patients through a series of imaging processing methods. An endoleak possibly forms in a location with high local wall stress. An improved stent graft (SG) structure is conceived accordingly by increasing the mechanical strength of the SG at peak wall stress locations. The presented analytical paradigm, as well as numerical analysis using patient-specific models, may be extended to other common human cardiovascular surgeries. PMID- 27660649 TI - A Modified Brain MR Image Segmentation and Bias Field Estimation Model Based on Local and Global Information. AB - Because of the poor radio frequency coil uniformity and gradient-driven eddy currents, there is much noise and intensity inhomogeneity (bias) in brain magnetic resonance (MR) image, and it severely affects the segmentation accuracy. Better segmentation results are difficult to achieve by traditional methods; therefore, in this paper, a modified brain MR image segmentation and bias field estimation model based on local and global information is proposed. We first construct local constraints including image neighborhood information in Gaussian kernel mapping space, and then the complete regularization is established by introducing nonlocal spatial information of MR image. The weighting between local and global information is automatically adjusted according to image local information. At the same time, bias field information is coupled with the model, and it makes the model reduce noise interference but also can effectively estimate the bias field information. Experimental results demonstrate that the proposed algorithm has strong robustness to noise and bias field is well corrected. PMID- 27660650 TI - Adjunctive use of modified Yunu-Jian in the non-surgical treatment of male smokers with chronic periodontitis: a randomized double-blind, placebo-controlled clinical trial. AB - BACKGROUND: Yunu-Jian (YJ) is a Chinese medicine (CM) heat purging formula, which is used to reduce wei huo (stomach-heat, SH) and enrich shen yin (kidney-yin, KY). This formula is also commonly used to manage diabetes mellitus and gum/oral inflammation. The activity of YJ can be modified or refined by the addition of other CM herbs and/or minor changes to one of its five key ingredients. The aim of this study was to evaluate the adjunctive use of modified YJ (mYJ) or YJ containing additional osteoblast-stimulating and inflammation-modulating CM herbs in the non-surgical periodontal treatment of smokers with chronic periodontitis in a randomized, double-blind, prospective, placebo-controlled study. METHODS: Healthy adult male smokers with untreated chronic periodontitis who showed CM syndrome of SH and KY deficiency (KYD) whilst attending a dental teaching hospital from October to December, 2005, were invited to participate in a randomized double-blind, placebo-controlled clinical trial. The trial itself involved the once-daily oral administration of a placebo or mYJ for 3 months as an adjunct to non-surgical periodontal therapy. Several periodontal parameters, including radiographic alveolar bone density, were measured by computer-assisted densitometric image analysis (CADIA) on selected sites, and CM signs of SH and KYD were followed from their baseline values to various time points up to 12 months or the end of study. RESULTS: Twenty-five smokers (consumed 25.0 +/- 15.3 smoking-pack years, ranged 7.5-80; aged 46.3 +/- 6.8 years) with periodontitis and SH and KYD were recruited (Placebo, n = 14; mYJ, n = 11). All of the participants showed good tolerance towards the CM recipe. All of the periodontal parameters had improved after 12-month follow-up, and no statistically significant differences were detected between the control group and test group, except for the higher CADIA values observed compared with the baseline at 12 months for test sites (P = 0.025). 4/3/3 test vs 14/13/13 control participants had persisting SH and KYD at 6, 9 and 12 months (P < 0.001), respectively. CONCLUSIONS: The adjunctive use of mYJ preserved the post-treatment increases in the radiographic alveolar bone density at the study sites and led to an overall improvement in SH and KYD compared with the controls. Trial registration HKU Clinical Trial Register, HKCTR-1848 (www.hkuctr.com/Study/Show/3acbf983831244d29d50b543540bf6e9). PMID- 27660651 TI - Psychosis and help-seeking behavior in rural KwaZulu Natal: unearthing local insights. AB - BACKGROUND: Growing interest in strategies regarding early intervention for psychosis has led to a parallel interest in understanding help-seeking behavior, especially in low- and middle-income countries (LMICs). Nevertheless, few LMIC studies have examined individuals with psychosis in non-urban, non-hospital settings. Using the perspective of formal and informal community service providers, we aimed to uncover descriptions of people with psychosis in a rural South African community and illuminate the potential complexities of their help seeking journeys. METHODS: We conducted a qualitative study of 40 key informant interviews and seven focus groups with stakeholders (traditional leaders, traditional healers, religious leaders, health care nurses, heads of non governmental organizations, schoolteachers, community caregivers) in a rural Zulu community (Vulindlela). Thematic analysis of the data was performed using the inductive analysis approach. RESULTS: Interviewees discussed 32 individuals with probable psychosis in their community and provided rich descriptions of their symptoms. A complex picture of help-seeking behavior, primarily involving informal mental health service providers, emerged. Over half of the reported cases had no contact with formal health services in the course of their help seeking journey; while more than two-thirds never attended a hospital and only 1 in 8 accessed a psychiatric hospital. CONCLUSIONS: Our results highlight the important role of informal care providers in LMICs as well as the need for more research on mental illness and local providers in non-hospital contexts. Community stakeholders can contribute to a fuller understanding of these issues, thereby assisting in the creation of appropriate and effective mental health interventions for rural South African communities like Vulindlela. PMID- 27660652 TI - A sustainable biorefinery to convert agricultural residues into value-added chemicals. AB - BACKGROUND: Animal wastes are of particular environmental concern due to greenhouse gases emissions, odor problem, and potential water contamination. Anaerobic digestion (AD) is an effective and widely used technology to treat them for bioenergy production. However, the sustainability of AD is compromised by two by-products of the nutrient-rich liquid digestate and the fiber-rich solid digestate. To overcome these limitations, this paper demonstrates a biorefinery concept to fully utilize animal wastes and create a new value-added route for animal waste management. RESULTS: The studied biorefinery includes an AD, electrocoagulation (EC) treatment of the liquid digestate, and fungal conversion of the solid fiber into a fine chemical-chitin. Animal wastes were first treated by an AD to produce methane gas for energy generation to power the entire biorefinery. The resulting liquid digestate was treated by EC to reclaim water. Enzymatic hydrolysis and fungal fermentation were then applied on the cellulose rich solid digestate to produce chitin. EC water was used as the processing water for the fungal fermentation. The results indicate that the studied biorefinery converts 1 kg dry animal wastes into 17 g fungal biomass containing 12 % of chitin (10 % of glucosamine), and generates 1.7 MJ renewable energy and 8.5 kg irrigation water. CONCLUSIONS: This study demonstrates an energy positive and freshwater-free biorefinery to simultaneously treat animal wastes and produce a fine chemical-chitin. The sustainable biorefinery concept provides a win-win solution for agricultural waste management and value-added chemical production. PMID- 27660654 TI - A message from the Editor-in-Chief. PMID- 27660653 TI - Development of simple random mutagenesis protocol for the protein expression system in Pichia pastoris. AB - BACKGROUND: Random mutagenesis is a powerful technique to obtain mutant proteins with different properties from the wild-type molecule. Error-prone PCR is often employed for random mutagenesis in bacterial protein expression systems, but has rarely been used in the methylotrophic yeast Pichia pastoris system, despite its significant advantages, mainly because large (MUg-level) amounts of plasmids are required for transformation. RESULTS: We developed a quick and easy technique for random mutagenesis in P. pastoris by sequential Phi29 DNA polymerase-based amplification methods, error-prone rolling circle amplification (RCA) and multiple displacement amplification (MDA). The methodology was validated by applying it for random mutation of the gene encoding cellulase from the basidiomycete Phanerochaete chrysosporium (PcCel6A), a key enzyme in degradation of cellulosic biomass. In the error-prone RCA step, the concentrations of manganese ion (Mn(2+)) and cellulase gene-containing plasmid were varied, and the products obtained under each condition were subjected to the second MDA step in the absence of Mn(2+). The maximum error rate was 2.6 mutations/kb, as evaluated from the results of large-scale sequencing. Several MUg of MDA products was transformed by electroporation into Pichia cells, and the activities of extracellularly expressed PcCel6A mutants towards crystalline and amorphous celluloses were compared with those of wild-type enzyme to identify key amino acid residues affecting degradation of crystalline cellulose. CONCLUSIONS: We present a rapid and convenient random mutagenesis method that does not require laborious steps such as ligation, cloning, and synthesis of specific primers. This method was successfully applied to the protein expression system in P. pastoris. PMID- 27660655 TI - Glenoid bone loss in primary and revision shoulder arthroplasty. AB - The management of glenoid bone loss is a major challenge in both complex primary and revision arthroplasty surgery. To deal with this problem, a number of techniques have been advocated, although there has been no previous systematic review of the literature. In the present review, we have attempted to identify a coherent strategy for addressing this problem, taking into account the degree of bone loss, the advantages and limits of standard implants, bone reconstruction techniques and the use of customized prostheses. PMID- 27660656 TI - Fractures of the greater tuberosity of the humerus: a study of associated rotator cuff injury and atrophy. AB - BACKGROUND: This is a retrospective prognostic study on soft tissue injury following isolated greater tuberosity (GT) fractures of the proximal humerus with respect to the relationship between rotator cuff tears and GT displacement. METHODS: Forty-three patients with isolated GT fractures were recruited and evaluated with a standardized interview and physical examination, quality of life and shoulder function questionnaires (Western Ontario Rotator Cuff Index, SF-12 Version 2, Constant, Quick-Disabilities of the Arm, Shoulder and Hand, Visual Analogue Scale), standard shoulder radiographs and an ultrasound. The main outcome measurements were: incidence of rotator cuff tears and atrophy, biceps pathology and sub-acromial impingement; superior displacement of the GT fragment; and questionnaire scores. RESULTS: Mean age was 57 years (31 years to 90 years) with a follow-up of 2.4 years (0.8 years to 6.8 years). In total, 16% had a full rotator cuff tear and 57% showed subacromial impingement on ultrasound. Full rotator cuff tears and supraspinatus fatty atrophy significantly correlated with decreased function and abduction strength. Significant atrophy (>50%) of the supraspinatus and infraspinatus, without a rotator cuff tear, was correlated with the worst function in the presence of a residual displacement of the greater tuberosity at the last-follow-up (7 mm). CONCLUSIONS: Residual displacement, full rotator cuff tear and muscle atrophy are associated with the worst outcomes. Soft tissue imaging could benefit patients with an unfavourable outcome after a GT fracture to treat soft tissue injury. PMID- 27660657 TI - Not all ultrasounds are created equal: general sonography versus musculoskeletal sonography in the detection of rotator cuff tears. AB - BACKGROUND: This cross-sectional analytic diagnostic accuracy study was designed to compare the accuracy of ultrasound performed by general sonographers in local radiology practices with ultrasound performed by an experienced musculoskeletal sonographer for the detection of rotator cuff tears. METHODS: In total, 238 patients undergoing arthroscopy who had previously had an ultrasound performed by both a general sonographer and a specialist musculoskeletal sonographer made up the study cohort. Accuracy of diagnosis was compared with the findings at arthroscopy. RESULTS: When analyzed as all tears versus no tears, musculoskeletal sonography had an accuracy of 97%, a sensitivity of 97% and a specificity of 95%, whereas general sonography had an accuracy of 91%, a sensitivity of 91% and a specificity of 86%. When the partial tears were split with those >= 50% thickness in the tear group and those < 50% thickness in the no-tear group, musculoskeletal sonography had an accuracy of 97%, a sensitivity of 97% and a specificity of 100% and general sonography had an accuracy of 85%, a sensitivity of 84% and a specificity of 87%. CONCLUSIONS: Ultrasound in the hands of an experienced musculoskeletal sonographer is highly accurate for the diagnosis of rotator cuff tears. General sonography has improved subsequent to earlier studies but remains inferior to an ultrasound performed by a musculoskeletal sonographer. PMID- 27660658 TI - Surgical treatment of a concurrent type 5 acromioclavicular joint dislocation and a failed anterior glenohumeral joint stabilization. AB - Traumatic glenohumeral joint dislocation and acromioclavicular joint subluxations tend to occur in young active males. Use of the coracoid process either as a transfer in recurrent instability or in suspensory reconstructions of the coracoclavicular ligaments have gained popularity. However this requires careful consideration in the event of concomitant injuries if they both require surgery. PMID- 27660659 TI - The clinical outcome and activity levels of patients under 55 years treated with distal humeral hemiarthroplasty for distal humeral fractures: minimum 2-year follow-up. AB - BACKGROUND: The aim of the present study was to describe the clinical outcomes and activity levels of young patients after distal humeral hemiarthroplasty (DHH). METHODS: Six patients under 55 years (mean 44 years; range 29 years to 52 years) treated with DHH at a mean postoperative time of 81 months (range 24 months to 133 months) were studied retrospectively. Two other patients had been revised for aseptic loosening and were excluded. RESULTS: The mean Mayo Elbow Score (MEPS) (88), Subjective Elbow Value (SEV) (89), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) (12) and American Shoulder and Elbow Surgeons (ASES) elbow pain (6), function (23) and satisfaction scores (9) were satisfactory. The mean University of California, Los Angeles (UCLA) activity score was 7.2. CONCLUSIONS: Although only rarely indicated, DHH has satisfactory clinical outcomes in young patients and allows a higher level of function than is generally advised after total elbow arthroplasty. PMID- 27660660 TI - The treatment of multidirectional instability of the shoulder with a rehabilitation program: Part 1. AB - BACKGROUND: The most commonly recommended initial treatment for multidirectional instability is a rehabilitation program. Although there is evidence to support the effect of conservative management on this condition, the published literature provides little information on the exercise parameters of such programs. In addition, current published rehabilitation programs for multidirectional instability do not focus on scapula stability or exercise drills into functional and sports-specific positions, which are often important aspects to consider in this patient population. METHODS: The aim of this paper (Part 1) is to outline the first two stages of a six-stage rehabilitation program for the conservative management of multidirectional instability with a focus on scapula control and exercise drills into functional positions. RESULTS AND CONCLUSIONS: This clinical protocol is currently being tested for efficacy as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry #ACTRN12613001240730). The information in this paper and additional online supplementary files will provide therapists with adequate detail to replicate the rehabilitation program in the clinical setting. PMID- 27660661 TI - Accelerated rehabilitation after arthroscopic Bankart repair in professional footballers. AB - BACKGROUND: Advances in arthroscopic surgery have resulted in biomechanically stronger repairs that might allow for accelerated rehabilitation protocols and hence faster return to play. Evidence for such regimes in the shoulder, particularly in elite athletes, is lacking. METHODS: This prospective single surgeon (PB) series included 34 professional footballers undergoing an accelerated rehabilitation programme following arthroscopic soft tissue stabilization subsequent to traumatic anterior shoulder dislocation. Data were collected on time to regain elevation range, external rotation range, return to play and rate of recurrence. RESULTS: Mean follow-up time was 4.8 years (range 2 years to 10 years). Full range of forward elevation was regained at a mean of 5 weeks (range 3 weeks to 7 weeks) and external rotation range (in neutral) at a mean of 6 weeks (range 4 weeks to 8 weeks). Mean return to play time was 11 weeks (range 9 weeks to 14 weeks). Three players (9%) reported a recurrent episode of dislocation at a mean of 19 months. CONCLUSIONS: An accelerated rehabilitation programme resulted in a return to play time of 11 weeks compared to previously reported times of between 5 months and 9 months in the contact sports population. A recurrence rate of 9% compares favourably to other published studies following similar surgery (5.1% to 28.6%) but which employed more conservative postoperative rehabilitation regimes. PMID- 27660662 TI - Simulation in shoulder surgery. AB - Simulation is a rapidly developing field in medical education. There is a growing need for trainee surgeons to acquire surgical skills in a cost-effective learning environment to improve patient safety and compensate for a reduction in training time and operative experience. Although simulation is not a replacement for traditional models of surgical training, and robust assessment metrics need to be validated before widespread use for accreditation, it is a useful adjunct that may ultimately lead to improving surgical outcomes for our patients. PMID- 27660663 TI - Insulin lispro low mixture twice daily vs basal insulin glargine once daily and prandial insulin lispro once daily as insulin intensification strategies in patients with type 2 diabetes: Latin American subpopulation analysis of a randomized trial. AB - BACKGROUND: This post hoc analysis examined the efficacy and safety of twice daily insulin lispro low mixture (LM25) and once-daily basal insulin glargine plus once-daily prandial insulin lispro (IGL) in a Latin American subpopulation with type 2 diabetes mellitus (T2DM). METHODS: A phase 4, randomized, open-label, parallel-arm trial included participants aged 18-75 years with T2DM taking once daily insulin glargine and stable doses of metformin and/or pioglitazone with glycated hemoglobin (HbA1c) 7.5-10.5 % and fasting plasma glucose <=121 mg/dL. Participants were randomized 1:1 to receive their stable dose of metformin and/or pioglitazone plus twice-daily LM25 or IGL for 24 weeks. The primary efficacy outcome was change in HbA1c after 24 weeks of treatment. Results from participants in Argentina, Brazil, and Mexico are presented here. RESULTS: 162 participants (80 LM25; 82 IGL) with mean +/- standard deviation (SD) age = 57.3 +/- 9.0 years and body mass index = 31.3 +/- 5.2 kg/m(2) were included. Mean +/- SD change in HbA1c from baseline to week 24 was -1.5 +/- 1.0 % (LM25) and -1.1 +/ 1.2 % (IGL). At week 24, 35.1 % (LM25) and 31.6 % (IGL) of participants achieved HbA1c <7.0 %. Mean +/- SD weight gain from baseline to week 24 was 2.4 +/- 2.9 kg in the LM25 group and 1.0 +/- 3.1 kg in the IGL group. The mean +/- SD rates of total hypoglycemia per year were 18.9 +/- 27.3 (LM25) and 21.6 +/- 31.1 (IGL). Rates of treatment-emergent adverse events were 46 % (LM25) and 39 % (IGL). CONCLUSIONS: Our results suggest that both LM25 and IGL are viable treatment options for insulin intensification in Latin American patients with T2DM with suboptimal glycemic control on basal insulin glargine. The safety and tolerability profiles of LM25 and IGL are consistent between this Latin American population and the global trial-level population. Trial registration NCT01175824. PMID- 27660664 TI - Pharmacokinetics of heroin and its metabolites in vitreous humor and blood in a living pig model. AB - Vitreous humor (VH) is an alternative matrix for drug analysis in forensic toxicology. However, little is known about the distribution of xenobiotics, such as opioids, into VH in living organisms. The aim of this study was to simultaneously measure heroin and metabolite concentrations in blood and VH after injection of heroin in a living pig model. Six pigs were under non-opioid anesthesia during the surgical operation and experiment. Ocular microdialysis was used to acquire dialysate from VH, and a venous catheter was used for blood sampling. Twenty milligrams of heroin was injected intravenously with subsequent sampling of blood and dialysate for 6 h. The samples were analyzed by ultra performance liquid chromatography-tandem mass spectrometry. Heroin was not detected in VH; 6-monoacetylmorphine (6-MAM) and morphine were first detected in VH after 60 min. The morphine concentration in VH thereafter increased throughout the experimental period. For 6-MAM, Cmax was reached after 230 min in VH. In blood, 6-MAM reached Cmax after 0.5 min, with a subsequent biphasic elimination phase. The blood and VH 6-MAM concentrations reached equilibrium after 2 h. In blood, morphine reached Cmax after 4.3 min, with a subsequent slower elimination than 6-MAM. The blood and VH morphine concentrations were in equilibrium about 6 h after injection of heroin. In conclusion, both 6-MAM and morphine showed slow transport into VH; detection of 6-MAM in VH did not necessarily reflect a recent intake of heroin. Because postmortem changes are expected to be small in VH, these experimental results could assist the interpretation of heroin deaths. PMID- 27660665 TI - Neonatal monocytes exhibit a unique histone modification landscape. AB - BACKGROUND: Neonates have dampened expression of pro-inflammatory cytokines and difficulty clearing pathogens. This makes them uniquely susceptible to infections, but the factors regulating neonatal-specific immune responses are poorly understood. Epigenetics, including histone modifications, can activate or silence gene transcription by modulating chromatin structure and stability without affecting the DNA sequence itself and are potentially modifiable. Histone modifications are known to regulate immune cell differentiation and function in adults but have not been well studied in neonates. RESULTS: To elucidate the role of histone modifications in neonatal immune function, we performed chromatin immunoprecipitation on mononuclear cells from 45 healthy neonates (gestational ages 23-40 weeks). As gestation approached term, there was increased activating H3K4me3 on the pro-inflammatory IL1B, IL6, IL12B, and TNF cytokine promoters (p < 0.01) with no change in repressive H3K27me3, suggesting that these promoters in preterm neonates are less open and accessible to transcription factors than in term neonates. Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) was then performed to establish the H3K4me3, H3K9me3, H3K27me3, H3K4me1, H3K27ac, and H3K36me3 landscapes in neonatal and adult CD14+ monocytes. As development progressed from neonate to adult, monocytes lost the poised enhancer mark H3K4me1 and gained the activating mark H3K4me3, without a change in additional histone modifications. This decreased H3K4me3 abundance at immunologically important neonatal monocyte gene promoters, including CCR2, CD300C, ILF2, IL1B, and TNF was associated with reduced gene expression. CONCLUSIONS: These results provide evidence that neonatal immune cells exist in an epigenetic state that is distinctly different from adults and that this state contributes to neonatal-specific immune responses that leaves them particularly vulnerable to infections. PMID- 27660667 TI - BMI, Body Image, Emotional Well-Being and Weight-Control Behaviors in Urban African American Adolescents. AB - IMPORTANCE: While urban African American adolescents face significant health disparities associated with overweight and obesity that follow them into adulthood; there is limited data on body image, emotional well-being, and weight control behaviors in this population to design effective public health interventions. OBJECTIVE: This study was designed to understand the association of weight status to adolescent weight control, body image, and emotional well being responses, in African American high school students. DESIGN/SETTING/PARTICIPANTS: The study cohort consisted of 776 students, mean age 15.8 years (+/-1.2). Data from Guidelines for Adolescent Preventive Services (GAPS) student surveys and anthropometric studies were collected at School-Based Health Centers. MAIN OUTCOME MEASURES: Associations between adolescent responses on the GAPS and body mass index (BMI) status (healthy weight: 5th to less than 85th percentile, overweight: 85th to less than 95th percentile, obese: 95th percentile or greater) were estimated using logistic regression and dose- response plots. RESULTS: There were statistically significant associations between BMI category and weight control (ranging from a mean 5.18 to 7.68 odds of obesity) and body image (3.40 to 13.26 odds of obesity) responses. Responses to weight control and body image questions exhibited a dose-response for odds of overweight and obesity. Feelings of depressed mood were associated with obesity (1.47 times the odds of obesity compared to students who did not endorse depressed mood; 95% CI, 1.01 to 2.13) but not overweight status. CONCLUSION AND RELEVANCE: Overweight and obese urban African American adolescents are more likely to screen positively on weight control risk behaviors and negative body image questions than their normal weight peers. The weight control and body image measures on the GAPS may provide information to identify youth in need of services and those motivated for brief school-based weight control interventions. PMID- 27660668 TI - Exposure to positively- and negatively-charged plasma cluster ions impairs IgE binding capacity of indoor cat and fungal allergens. AB - BACKGROUND: Environmental control to reduce the amount of allergens in a living place is thought to be important to avoid sensitization to airborne allergens. However, efficacy of environmental control on inactivation of airborne allergens is not fully investigated. We have previously reported that positively- and negatively-charged plasma cluster ions (PC-ions) reduce the IgE-binding capacity of crude allergens from Japanese cedar pollen as important seasonal airborne allergens. Cat (Felis domesticus) and fungus (Aspergillus fumigatus) are also important sources of common airborne allergens in living spaces throughout the year, and early sensitization with those allergens is considered to be a risk factor for future development of allergic rhinitis, pollinosis and asthma. The aim of this study is to examine whether the PC-ions reduce the IgE-binding capacity of a cat major allergen (Fel d 1) and fungal allergens in an experimental condition. METHODS: Fel d 1, crude fungal extract, or a fungal major allergen Asp f 1, was treated with PC-ions for 6 h in an experimental cylindrical apparatus. Sham-treated allergens were prepared in the same experimental apparatus without generation of PC-ions. The degradation of the PC-ions-treated Fel d 1 was analyzed by SDS-PAGE, and the IgE-binding capacity of the PC-ions treated allergens was analyzed by ELISA inhibition assay. RESULTS: Exposure of Fel d 1, crude fungal extract and Asp f 1 to PC-ions significantly decreased protein content of Fel d 1 or Asp f 1, respectively. SDS-PAGE analysis suggested that the decreased Fel d 1 content upon exposure with PC-ions was attributable to protein degradation. ELISA inhibition indicated that the PC-ions treatment significantly impaired IgE-binding capacities of Fel d 1, crude fungal allergens, and Asp f 1 compared to sham treatment. DISCUSSION: Our data suggest that treatment with PC-ions not only reduce indoor cat and fungal allergens, but also impair their allergenicity. CONCLUSION: These results suggest that environmental control with PC-ions is useful for inactivation of indoor cat and fungal allergens. PMID- 27660666 TI - SEPT9 and SHOX2 DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas. AB - BACKGROUND: Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of SEPT9 and SHOX2 has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions. RESULTS: Assessment of promoter methylation of SEPT9 distinguished adenomas and CRC from controls as well as advanced from non advanced adenomas (all p < 0.001). Correspondingly, SHOX2 methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues (p < 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of the SEPT9 gene locus. CONCLUSIONS: SEPT9/SHOX2 methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine. PMID- 27660669 TI - Short-term time step convergence in a climate model. AB - This paper evaluates the numerical convergence of very short (1 h) simulations carried out with a spectral-element (SE) configuration of the Community Atmosphere Model version 5 (CAM5). While the horizontal grid spacing is fixed at approximately 110 km, the process-coupling time step is varied between 1800 and 1 s to reveal the convergence rate with respect to the temporal resolution. Special attention is paid to the behavior of the parameterized subgrid-scale physics. First, a dynamical core test with reduced dynamics time steps is presented. The results demonstrate that the experimental setup is able to correctly assess the convergence rate of the discrete solutions to the adiabatic equations of atmospheric motion. Second, results from full-physics CAM5 simulations with reduced physics and dynamics time steps are discussed. It is shown that the convergence rate is 0.4-considerably slower than the expected rate of 1.0. Sensitivity experiments indicate that, among the various subgrid-scale physical parameterizations, the stratiform cloud schemes are associated with the largest time-stepping errors, and are the primary cause of slow time step convergence. While the details of our findings are model specific, the general test procedure is applicable to any atmospheric general circulation model. The need for more accurate numerical treatments of physical parameterizations, especially the representation of stratiform clouds, is likely common in many models. The suggested test technique can help quantify the time-stepping errors and identify the related model sensitivities. PMID- 27660670 TI - Genome sequence of Candidatus Arsenophonus lipopteni, the exclusive symbiont of a blood sucking fly Lipoptena cervi (Diptera: Hippoboscidae). AB - Candidatus Arsenophonus lipopteni (Enterobacteriaceae, Gammaproteobacteria) is an obligate intracellular symbiont of the blood feeding deer ked, Lipoptena cervi (Diptera: Hippoboscidae). The bacteria reside in specialized cells derived from host gut epithelia (bacteriocytes) forming a compact symbiotic organ (bacteriome). Compared to the closely related complex symbiotic system in the sheep ked, involving four bacterial species, Lipoptena cervi appears to maintain its symbiosis exclusively with Ca. Arsenophonus lipopteni. The genome of 836,724 bp and 24.8 % GC content codes for 667 predicted functional genes and bears the common characteristics of sequence economization coupled with obligate host dependent lifestyle, e.g. reduced number of RNA genes along with the rRNA operon split, and strongly reduced metabolic capacity. Particularly, biosynthetic capacity for B vitamins possibly supplementing the host diet is highly compromised in Ca. Arsenophonus lipopteni. The gene sets are complete only for riboflavin (B2), pyridoxine (B6) and biotin (B7) implying the content of some B vitamins, e.g. thiamin, in the deer blood might be sufficient for the insect metabolic needs. The phylogenetic position within the spectrum of known Arsenophonus genomes and fundamental genomic features of Ca. Arsenophonus lipopteni indicate the obligate character of this symbiosis and its independent origin within Hippoboscidae. PMID- 27660672 TI - Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma. AB - Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). In addition, hepatoma upregulated protein (HURP) is a cellular oncogene that is upregulated in a majority of HCC cases. We highlight here recent findings demonstrating a link between HBx, HURP and anti apoptosis effects observed in cisplatin-treated HCC cells. We observed that Hep3B cells overexpressing HBx display increased HURP mRNA and protein levels, and show resistance to cisplatin-induced apoptosis. Knockdown of HURP in HBx-expressing cells reverses this effect, and sensitizes cells to cisplatin. The anti-apoptotic effect of HBx requires activation of the p38/MAPK pathway as well as expression of SATB1, survivin and HURP. Furthermore, silencing of HURP using short-hairpin RNA promotes accumulation of p53 and reduces cell proliferation in SK-Hep-1 cells (p53(+/-)), whereas these effects are not observed in p53-mutant Mahlavu cells. Similarly, HURP silencing does not affect the proliferation of H1299 lung carcinoma cells or Hep3B HCC cells which lack p53. Silencing of HURP sensitizes SK-Hep-1 cells to cisplatin. While HURP overexpression promotes p53 ubiquitination and degradation by the proteasome, HURP silencing reverses these effects. Inoculation of SK-Hep-1 cancer cells in which HURP has been silenced produces smaller tumors than control in nude mice. Besides, gankyrin, a positive regulator of the E3 ubiquitin ligase MDM2, is upregulated following HURP expression, and silencing of gankyrin reduces HURP-mediated downregulation of p53. In addition, we observed a positive correlation between HURP and gankyrin protein levels in HCC patients (r (2) = 0.778; n = 9). These findings suggest a role for the viral protein HBx and the host protein HURP in preventing p53 mediated apoptosis during cancer progression and establishment of chemoresistance. PMID- 27660673 TI - CD36 genetic variation, fat intake and liver fibrosis in chronic hepatitis C virus infection. AB - AIM: To analyze the association of the CD36 polymorphism (rs1761667) with dietary intake and liver fibrosis (LF) in chronic hepatitis C (CHC) patients. METHODS: In this study, 73 patients with CHC were recruited. The CD36 genotype (G > A) was determined by a TaqMan real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography (Fibroscan((r))) and APRI score was classified as mild LF (F1-F2) and advanced LF (F3-F4). RESULTS: Overall, the CD36 genotypic frequencies were AA (30.1%), AG (54.8%), and GG (15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase (AST) serum values were higher in AA genotype carriers compared to non-AA carriers (91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST (beta = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG (OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes (OR = 3.52, 95%CI: 1.18-10.45, P = 0.02). CONCLUSION: This study suggests that the CD36 (rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients. PMID- 27660671 TI - Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation. AB - Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT. PMID- 27660675 TI - Hydatid cyst of the gallbaldder: A systematic review of the literature. AB - AIM: To evaluate all the references about primary gallbladder hidatidosis looking for best treatment evidence. METHODS: Search: 1966-2015 in MEDLINE, Cochrane Library, SciELO, and Tripdatabase. KEY WORDS: "gallabladder hydatid disease" and "gallbladder hydatid cyst". We found 124 papers in our searches but only 14 papers including 16 cases were about hydatid cyst of the gallbladder (GBHC). RESULTS: Eight cases of GBHC were women and seven men. One not mentioned. Median age was 48.3 years. The most frequent clinical symptom was abdominal pain (94%) usually in the right upper quadrant. Ultrasound was performed in ten patients (62.5%) but in most cases a combination of several techniques was performed. The location of the cysts was intravesicular in five patients. Five patients presented GBHC and liver hydatid cysts. Two patients presented cholelithiasis and one choledocholithiasis. The most frequent surgical technique was cholecystectomy by laparotomy (81.25%). Simultaneous surgery of liver cysts was carried out in five cases. Eleven patients did not present postoperative complications, but one died. The mean hospital stay was seven days. No recurrence of GBHC was recorded. CONCLUSION: In GBHC, the most frequent symptom is right hypocondrium pain (evidence level V). Best diagnostic methods are ultrasound and computed tomography (level V, grade D). Suggested treatment is open cholecystectomy and postoperative albendazole (level V, grade D) obtaining good clinical results and none relapses. PMID- 27660674 TI - Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A Delphi technique-based consensus. AB - AIM: To propose several alternatives treatment of type 1 hepatorenal syndrome (HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension. METHODS: A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature. Each expert was designated to review and answer a question. They generated draft statements for evaluation by all the experts. Additional input was obtained from medical community. In order to reach consensus, a modified three-round Delphi technique method was used. According to United States Preventive Services Task Force criteria, the quality of the evidence and level of recommendation supporting each statement was graded. RESULTS: Nine questions were formulated. The available evidence was evaluated considering its quality, number of patients included in the studies and the consistency of its results. The generated questions were answered by the expert panel with a high level of agreement. Thus, a therapeutic algorithm was generated. The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice. On the other hand the use of the combination of octreotide, midodrine and albumin without vasoconstrictors was discouraged. The role of several other options was also evaluated and the available evidence was explored and discussed. Liver transplantation is considered the definitive treatment for HRS-1. The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature, the quality of the evidence and the benefits, adverse effects and availability of the therapeutic tools described. CONCLUSION: Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1. PMID- 27660676 TI - Cholangiocarcinoma, gone without the Wnt? AB - Cholangiocarcinoma (CCA) is a relatively rare malignancy of the intra- or extra hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7B and Wnt10A were found to be highly overexpressed in human CCA tissue. Wnt7B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68(+) macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA. Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10a increased during the (pre-cancerous) regenerative phase, while Wnt7b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion, eliminating a major source of Wnt7b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover, specific inhibitors of the canonical Wnt pathway (ICG-001 and C-59) caused reduction of tumor area and number, in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt driven tumor. Modulation of Wnt signaling, alone or in combination with surgical or chemotherapy approaches, holds promise in the management of this fatal malignancy. PMID- 27660677 TI - Role of epidural anesthesia in a fast track liver resection protocol for cirrhotic patients - results after three years of practice. AB - AIM: To evaluate the potential benefits and risks of the use of epidural anaesthesia within an enhanced recovery protocol in this specific subpopulation. METHODS: A retrospective review was conducted, including all cirrhotic patients who underwent open liver resection between January 2013 and December 2015 at Bologna University Hospital. Patients with an abnormal coagulation profile contraindicating the placement of an epidural catheter were excluded from the analysis. The control group was composed by patients refusing epidural anaesthesia. RESULTS: Of the 183 cirrhotic patients undergoing open liver resections, 57 had contraindications to the placement of an epidural catheter; of the remaining 126, 86 patients received general anaesthesia and 40 combined anaesthesia. The two groups presented homogeneous characteristics. Intraoperatively the metabolic data did not differ between the two groups, whilst the epidural group had a lower mean arterial pressure (P = 0.041) and received more colloid infusions (P = 0.007). Postoperative liver and kidney function did not differ significantly. Length of mechanical ventilation (P = 0.003) and hospital stay (P = 0.032) were significantly lower in the epidural group. No complications related to the epidural catheter placement or removal was recorded. CONCLUSION: The use of Epidural Anaesthesia within a fast track protocol for cirrhotic patients undergoing liver resections had a positive impact on the patient's outcomes and comfort as demonstrated by a significantly lower length of mechanical ventilation and hospital stay in the epidural group. The technique appears to be safely manageable in this fragile population even though these results need confirmation in larger studies. PMID- 27660678 TI - Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis. AB - AIM: To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS: Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS: The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION: This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed. PMID- 27660679 TI - Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver? AB - Hepatocellular adenoma (HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast enhanced ultrasonography (CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A (SAA), focal positive for glutamine synthetase, diffuse and strong positive for C reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm. PMID- 27660680 TI - Predictive potential of IL-28B genetic testing for interferon based hepatitis C virus therapy in Pakistan: Current scenario and future perspective. AB - In Pakistan which ranked second in terms of hepatitis C virus (HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy response prediction. Interleukin 28B (IL-28B) genetic testing is widely used throughout the world for interferon based therapy prediction for HCV patients and is quite helpful not only for health care workers but also for the patients. There is a strong relationship between single nucleotide polymorphisms at or near the IL-28B gene and the sustained virological response with pegylated interferon plus ribavirin treatment for chronic hepatitis C. Pakistan is a resource limited country, with very low per capita income and there is no proper social security (health insurance) system. The allocated health budget by the government is very low and is used on other health emergencies like polio virus and dengue virus infection. Therefore it is proposed that there should be a well established diagnostic test on the basis of IL-28B which can predict the antiviral therapy response to strengthen health care set-up of Pakistan. This test once established will help in better management of HCV infected patients. PMID- 27660681 TI - Identification and Structural Characterization of Three New Metabolites of Bupropion in Humans. AB - Bupropion is a widely used antidepressant and the recommended CYP2B6 probe drug. However, current understanding of bupropion elimination pathways is limited. Bupropion has three active circulating metabolites, OH-bupropion, threohydrobupropion, and erythrohydrobupropion, but together with bupropion these metabolites and their conjugates in urine represent only 23% of the dose, and the majority of the elimination pathways of bupropion result in uncharacterized metabolites. The aim of this study was to determine the structures of the uncharacterized bupropion metabolites using human clinical samples and in vitro incubations. Three new metabolites, 4'-OH-bupropion, erythro-4'-OH hydrobupropion, and threo-4'-OH-hydrobupropion, were detected in human liver microsome incubations and were isolated from human urine. The structures of the metabolites were confirmed via comparison of UV absorbance, NMR spectra, and mass spectral data to those of the synthesized standards. In total, these metabolites represented 24% of the drug related material excreted in urine. PMID- 27660683 TI - Treatment of Pain with Spirocylic Cyclohexane Derivatives Having Dual Specificity for ORL-1 and MU-Opioid Receptors. PMID- 27660682 TI - The Added Value of Assessing Ligand-Receptor Binding Kinetics in Drug Discovery. AB - In the past decade drug research community has started to appreciate the indispensable role of ligand-receptor binding kinetics (BK) in drug discovery. Next to the classical equilibrium-based drug evaluation process with affinity and potency values as outcomes, kinetic investigation of the ligand-receptor interaction can aid compound triage in the hit-to-lead campaign and provide additional information to understand the molecular mechanism of drug action. Translational models incorporating BK are emerging as well, which represent powerful tools for the prediction of in vivo effects. In this viewpoint we will summarize some recent findings and discuss and emphasize the added value of ligand-receptor binding kinetics in drug research. PMID- 27660684 TI - PPAR Agonists, Compounds, Pharmaceutical Compositions, and Methods of Use Thereof. PMID- 27660685 TI - (18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography. AB - Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications. PMID- 27660686 TI - Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a Potent I Kur Inhibitor. AB - A new series of phenylquinazoline inhibitors of Kv 1.5 is disclosed. The series was optimized for Kv 1.5 potency, selectivity versus hERG, pharmacokinetic exposure, and pharmacodynamic potency. 5-Phenyl-N-(pyridin-2-ylmethyl)-2 (pyrimidin-5-yl)quinazolin-4-amine (13k) was identified as a potent and ion channel selective inhibitor with robust efficacy in the preclinical rat ventricular effective refractory period (VERP) model and the rabbit atrial effective refractory period (AERP) model. PMID- 27660687 TI - Polar Recognition Group Study of Keap1-Nrf2 Protein-Protein Interaction Inhibitors. AB - Directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has emerged as an attractive way to activate Nrf2, and Keap1-Nrf2 PPI inhibitors have been proposed as potential agents to relieve inflammatory and oxidative stress diseases. In this work, we investigated the diacetic moiety around the potent Keap1-Nrf2 PPI inhibitor DDO1018 (2), which was reported by our group previously. Exploration of bioisosteric replacements afforded the ditetrazole analog 7, which maintains the potent PPI inhibition activity (IC50 = 15.8 nM) in an in vitro fluorescence polarization assay. Physicochemical property determination demonstrated that ditetrazole replacement can improve the drug-like property, including elevation of pK a, log D, and transcellular permeability. Additionally, 7 is more efficacious than 2 on inducing the expression of Nrf2-dependent gene products in cells. This study provides an alternative way to replace the diacetic moiety and occupy the polar subpockets in Keap1, which can benefit the subsequent development of Keap1-Nrf2 PPI inhibitor. PMID- 27660688 TI - Modifications of a Nanomolar Cyclic Peptide Antagonist for the EphA4 Receptor To Achieve High Plasma Stability. AB - EphA4 is a receptor tyrosine kinase with a critical role in repulsive axon guidance and synaptic function. However, aberrant EphA4 activity can inhibit neural repair after injury and exacerbate neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's. We previously identified the cyclic peptide APY-d2 (APYCVYRbetaASWSC-nh2, containing a disulfide bond) as a potent and selective EphA4 antagonist. However, APY-d2 lacks sufficient plasma stability to be useful for EphA4 inhibition in vivo through peripheral administration. Using structure-activity relationship studies, we show that protecting the peptide N-terminus from proteolytic degradation dramatically increases the persistence of the active peptide in plasma and that a positively charged peptide N-terminus is essential for high EphA4 binding affinity. Among several improved APY-d2 derivatives, the cyclic peptides APY-d3 (betaAPYCVYRbetaASWSC-nh2) and APY-d4 (betaAPYCVYRbetaAEWEC-nh2) combine high stability in plasma and cerebrospinal fluid with slightly enhanced potency. These properties make them valuable research tools and leads toward development of therapeutics for neurological diseases. PMID- 27660689 TI - Cellular Activity of New Small Molecule Protein Arginine Deiminase 3 (PAD3) Inhibitors. AB - The protein arginine deiminases (PADs) catalyze the post-translational deimination of arginine side chains. Multiple PAD isozymes have been characterized, and abnormal PAD activity has been associated with several human disease states. PAD3 has been characterized as a modulator of cell growth via apoptosis inducing factor and has been implicated in the neurodegenerative response to spinal cord injury. Here, we describe the design, synthesis, and evaluation of conformationally constrained versions of the potent and selective PAD3 inhibitor 2. The cell activity of representative inhibitors in this series was also demonstrated for the first time by rescue of thapsigargin-induced cell death in PAD3-expressing HEK293T cells. PMID- 27660690 TI - Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3beta. AB - Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3beta, allow the systematic synthesis of related fragment analogues to explore fragment level structure-activity relationship, and finally lead to the synthesis of a more potent compound. PMID- 27660691 TI - Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design. AB - In an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an autotaxin IC50 of 500 nM. X-ray crystallography enabled the optimization to a lead compound that demonstrated favorable potency (IC50 = 2 nM), PK properties, and a robust PK/PD relationship. PMID- 27660692 TI - Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-gamma Inhibitor (IPI 549) as an Immuno-Oncology Clinical Candidate. AB - Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-gamma (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-gamma mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors. PMID- 27660693 TI - T-3364366 Targets the Desaturase Domain of Delta-5 Desaturase with Nanomolar Potency and a Multihour Residence Time. AB - Delta-5 desaturase (D5D) catalyzes the conversion from dihomo-gamma linoleic acid (DGLA) to arachidonic acid (AA). DGLA and AA are common precursors of anti- and pro-inflammatory eicosanoids, respectively, making D5D an attractive drug target for inflammatory-related diseases. Despite several reports on D5D inhibitors, their biochemical mechanisms of action (MOAs) remain poorly understood, primarily due to the difficulty in performing quantitative enzymatic analysis. Herein, we report a radioligand binding assay to overcome this challenge and characterized T 3364366, a thienopyrimidinone D5D inhibitor, by use of the assay. T-3364366 is a reversible, slow-binding inhibitor with a dissociation half-life in excess of 2.0 h. The long residence time was confirmed in cellular washout assays. Domain swapping experiments between D5D and D6D support [(3)H]T-3364366 binding to the desaturase domain of D5D. The present study is the first to demonstrate biochemical MOA of desaturase inhibitors, providing important insight into drug discovery of desaturase enzymes. PMID- 27660694 TI - Entrapment neuropathies in diabetes mellitus. AB - Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features. PMID- 27660696 TI - Evidence for current diagnostic criteria of diabetes mellitus. AB - Diabetes mellitus is a non-communicable metabolic derangement afflicting several millions of individuals globally. It is associated with several micro and macrovascular complications and is also a leading cause of mortality. The unresolved issue is that of definition of the diagnostic threshold for diabetes. The World Health Organization and the American Diabetes Association (ADA) have laid down several diagnostic criteria for diagnosing diabetes and prediabetes based on the accumulating body of evidence.This review has attempted to analyse the scientific evidence supporting the justification of these differing criteria. The evidence for diagnosing diabetes is strong, and there is a concordance between the two professional bodies. The controversy arises when describing the normal lower limit of fasting plasma glucose (FPG) with little evidence favouring the reduction of the FPG by the ADA. Several studies have also shown the development of complications specific for diabetes in patients with prediabetes as defined by the current criteria though there is a significant overlap of such prevalence in individuals with normoglycemia. Large multinational longitudinal prospective studies involving subjects without diabetes and retinopathy at baseline will ideally help identify the threshold of glycemic measurements for future development of diabetes and its complications. PMID- 27660697 TI - In vivo corneal confocal microscopy in diabetes: Where we are and where we can get. AB - In vivo corneal confocal microscopy (IVCCM) is a novel, reproducible, easy and noninvasive technique that allows the study of the different layers of the cornea at a cellular level. As cornea is the most innervated organ of human body, several studies investigated the use of corneal confocal microscopy to detect diabetic neuropathies, which are invalidating and deadly complications of diabetes mellitus. Corneal nerve innervation has been shown impaired in subjects with diabetes and a close association between damages of peripheral nerves due to the diabetes and alterations in corneal sub-basal nerve plexus detected by IVCCM has been widely demonstrated. Interestingly, these alterations seem to precede the clinical onset of diabetic neuropathies, paving the path for prevention studies. However, some concerns still prevent the full implementation of this technique in clinical practice. In this review we summarize the most recent and relevant evidences about the use of IVCCM for the diagnosis of peripheral sensorimotor polyneuropathy and of autonomic neuropathy in diabetes. New perspectives and current limitations are also discussed. PMID- 27660698 TI - Diabetes mellitus and cognitive impairments. AB - There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer's disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings. PMID- 27660699 TI - Sex-related factors influence expression of mood-related genes in the basolateral amygdala differentially depending on age and stress exposure. AB - BACKGROUND: Women are twice as likely to be diagnosed with major depressive disorder (MDD) compared to men, but the molecular mechanisms underlying this sex difference are unclear. Previous studies in the human postmortem brain suggest dysfunction in basolateral amygdala (BLA) inhibitory gamma-aminobutyric acid (GABA) signaling and brain-derived neurotrophic factor (BDNF) function, specifically in females with MDD. METHODS: We investigated the effects of sex chromosome complement, developmental gonadal sex, and circulating testosterone on expression of 3 GABA-related and 2 BDNF-related genes in the BLA using three cohorts of four core genotypes (FCG) mice. Cohort 1 included gonadally intact pre pubertal FCG mice; results were analyzed using two-way ANOVA (sex chromosome complement-by-gonadal sex). We examined the same genes under adult non-stressed (cohort 2) and chronically stressed conditions (cohort 3). The results for cohorts 2 and 3 were analyzed by three-way ANOVA (sex chromosome complement-by gonadal sex-by-hormone). The use of heatmaps and Spearman correlation of BLA gene expression and anxiety-like behavior provides a global interpretation of gene expression patterns. RESULTS: In weanlings, we found an effect of sex chromosome complement, with lower expression of GABA/BDNF-related genes in XY mice. Most of these effects did not persist into adulthood, although a number of interesting interactions between organizational and activational effects of hormones emerged. In our adult cohorts, we found that testosterone had different effects depending on stress conditions and/or gonadal sex. Notably, in our chronically stressed adults, we found that the BLA pattern of gene expression for the GABA-related gene, somatostatin (Sst), matched the anxiety-like behavior pattern (i.e., lower Sst and higher anxiety-like behavior in XY mice, while testosterone increased Sst and decreased anxiety-like behavior). Additionally, increased Sst gene expression was correlated with decreased anxiety-like behavior. CONCLUSIONS: Sex chromosome complement is an important factor modulating expression of mood-related genes during pre-pubertal development. The observed sex differences under chronically stressed conditions suggest that different molecular profiles may characterize male and female MDD. Our findings here for Sst are especially interesting, and suggest an underlying XY vulnerability that is typically compensated for by circulating testosterone in "normal" males. Without testosterone, women may have lower SST expression in the amygdala, resulting in increased MDD vulnerability. PMID- 27660700 TI - Focussing Attention on Oneself Increases the Perception of Being Observed by Others. AB - Patients with Social Anxiety Disorder (SAD) often report elevated levels of self focussed evaluative attention (SFEA), and seem excessively concerned with being observed by others. This study tested whether SFEA increases the perception of being observed by others. A sample of 52 high and 52 low socially anxious participants estimated the percentage of people 'looking at you' in several matrices of faces. A control task used matrices of clocks. SFEA was manipulated. As predicted, increasing SFEA led to significantly higher estimates of people 'looking at you' in both groups. Estimates on the control task were not affected by SFEA, thus the effects appear specific to social stimuli. These findings suggest that the increased levels of SFEA that characterise patients with SAD could contribute to their enhanced perception of being observed by others. The findings have implications for the role of attention training in the treatment of SAD. PMID- 27660702 TI - Influence of main dietary chemical constituents on the in vitro gas and methane production in diets for dairy cows. AB - BACKGROUND: Modification of chemical composition of diets fed to dairy cows might be a good strategy to reduce methane (CH4) production in the rumen. Notable reductions of CH4 production compared to conventional high-roughages rations were more frequently observed for very concentrated diets or when fat supplements were used. In these cases, the reduction in the gas emission was mainly a consequence of an overall impairment of rumen function with a reduction of fiber digestibility. These strategies do not always comply with feeding standards used in intensive dairy farms and they are usually not applied owing to the risks of negative health and economic consequences. Thus, the present study evaluated the effects of seven commercial diets with contents of neutral detergent fiber (NDF), protein and lipids ranging 325 to 435 g/kg DM, 115 to 194 g/kg DM, and 26 to 61 g/kg DM, respectively, on in vitro degradability, gas (GP), and CH4 production. RESULTS: In this experiment, changes in the dietary content of NDF, crude protein (CP) and lipids were always obtained at the expense or in favor of starch. A decreased of the dietary NDF content increased NDF (NDFd) and true DM (TDMd) degradability, and increased CH4 production per g of incubated DM (P < 0.001), but not that per g of TDMd. An increase of the dietary CP level did not change in vitro NDFd and TDMd, decreased GP per g of incubated DM (P < 0.001), but CH4 production per g of TDMd was not affected. An increased dietary lipid content reduced NDFd, TDMd, and GP per g of incubated DM, but it had no consequence on CH4 production per g of TDMd. CONCLUSIONS: It was concluded that, under commercial conditions, changes in dietary composition would produce small or negligible alterations of CH4 production per unit of TDMd, but greater differences in GP and CH4 production would be expected when these amounts are expressed per unit of DM intake. The use of TDMd as a standardizing parameter is proposed to account for possible difference in DM intake and productivity. PMID- 27660703 TI - Association between distorted body image and changes in weight status among normal weight preadolescents in Japan: a population-based cohort study. AB - BACKGROUND: Distorted body image may be important risk factors for being underweight and overweight. The objective of this study was to investigate the association between having a distorted body image and being overweight or underweight among normal weight preadolescents in a population-based cohort study in Japan for each sex. METHODS: The study participants were 1431 normal weight fourth-grade students (age range: 9-10 years) in Ina town, Japan from 2002 to 2007. The height and weight of each student were measured while they were in the fourth grade (at baseline) and seventh grade (3 years later). Childhood underweight and overweight were defined using the body mass index cut-off points proposed by the International Obesity Task Force. Information regarding the self perceived weight status of each student at baseline was collected using a self administered questionnaire. Children who were normal weight but perceived themselves as heavy or thin were regarded as having a distorted body images. A logistic regression model was used to calculate the odds ratios (ORs) and 95 % confidence interval (95 % CI) for being overweight or underweight 3 years later among those having a distorted body image at baseline. RESULTS: Both boys and girls who perceived themselves to be heavy at baseline were at a statistically significantly greater risk of being overweight 3 years later as compared to boys and girls, respectively, who identified as being at a normal weight at baseline (boys: adjusted OR: 4.66, 95 % CI: 1.01-21.48; girls: 3.88, 1.56-9.65). Both boys and girls who perceived oneself to be thin at baseline were at a statistically significantly greater risk of bring underweight 3 years later as compared to boys and girls, respectively, who identified as being at a normal weight at baseline (boys: 5.51, 2.20-13.80; girls: 2.93, 1.40-6.11). CONCLUSION: The results of the present study suggest that having a distorted body image in preadolescence is associated with being overweight or underweight in adolescence, among boys and girls, separately. Therefore, education regarding self-perceived weight could be important to help prevent underweight and overweight/obesity among preadolescent boys and girls in Japan. PMID- 27660701 TI - American Society for Enhanced Recovery (ASER) and Perioperative Quality Initiative (POQI) joint consensus statement on perioperative fluid management within an enhanced recovery pathway for colorectal surgery. AB - BACKGROUND: Enhanced recovery may be viewed as a comprehensive approach to improving meaningful outcomes in patients undergoing major surgery. Evidence to support enhanced recovery pathways (ERPs) is strong in patients undergoing colorectal surgery. There is some controversy about the adoption of specific elements in enhanced recovery "bundles" because the relative importance of different components of ERPs is hard to discern (a consequence of multiple simultaneous changes in clinical practice when ERPs are initiated). There is evidence that specific approaches to fluid management are better than alternatives in patients undergoing colorectal surgery; however, several specific questions remain. METHODS: In the "Perioperative Quality Initiative (POQI) Fluids" workgroup, we developed a framework broadly applicable to the perioperative management of intravenous fluid therapy in patients undergoing elective colorectal surgery within an ERP. DISCUSSION: We discussed aspects of ERPs that impact fluid management and made recommendations or suggestions on topics such as bowel preparation; preoperative oral hydration; intraoperative fluid therapy with and without devices for goal-directed fluid therapy; and type of fluid. PMID- 27660695 TI - Update on the treatment of type 2 diabetes mellitus. AB - To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus (T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade. PMID- 27660704 TI - Postoperative use of hypnotics is associated with increased length of stay after uncomplicated surgery for colorectal cancer. AB - BACKGROUND/AIMS: Hypnotics are used to treat perioperative sleep disorders. These drugs are associated with a higher risk of adverse effects among patients undergoing surgery. This study aims to quantify the use of hypnotics and factors influencing the administration of hypnotics in relation to colorectal cancer surgery. METHOD: A retrospective cohort study of 1979 patients undergoing colorectal cancer surgery. RESULTS: In all, 381 patients (19%) received new treatment with hypnotics. Two of the six surgical centres used hypnotics less often (odds ratio (95% confidence interval), 0.24 (0.16-0.38) and 0.20 (0.12 0.35)). Active smokers (odds ratio (95% confidence interval), 1.57 (1.11-2.24)) and patients receiving perioperative blood transfusion (odds ratio (95% confidence interval), 1.58 (1.10-2.26)) had increased likelihood of receiving hypnotics. In the uncomplicated cases, a multivariable linear regression analysis showed that consumption of hypnotics postoperatively was significantly associated with increased length of stay (1.5 (0.9-2.2) days). CONCLUSION: One in five patients began treatment with hypnotics after colorectal cancer surgery. Postoperative use of hypnotics was associated with an increased length of stay for uncomplicated cases of colorectal cancer surgery. PMID- 27660705 TI - Current clinical trials testing the combination of immunotherapy with radiotherapy. AB - Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress. We also address issues pertaining to the optimal incorporation of immunotherapy with radiation, including sequencing of treatment, radiation dosing and evaluation of clinical trial endpoints. PMID- 27660707 TI - Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy. AB - With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma. Herein, we review the development of T-VEC, and suggest how it fits into the in the current clinical treatment paradigm, and provide pearls for drug preparation, administration, and monitoring of response to therapy. PMID- 27660706 TI - A retrospective analysis of High-Dose Interleukin-2 (HD IL-2) following Ipilimumab in metastatic melanoma. AB - BACKGROUND: High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading to long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a larger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent therapeutic options need to be explored. METHODS: The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL 2 after treatment with ipilimumab or without prior ICB. Patient characteristics, toxicity and efficacy were analyzed. RESULTS: A total of 52 metastatic melanoma patients were treated with high dose IL-2 after ipilimumab and 276 patients were treated with high dose IL-2 without prior ICB. The overall response rate in the prior ipilimumab group was 21 % as compared to 12 % in the group that had not received prior ipilimumab. The median overall survival, measured from the initiation of HD IL-2 therapy, was 19.3 months in the prior ipilimumab group and 19.4 months in the no prior ICB group. Toxicities observed on HD IL-2 were relatively equivalent between the groups although there were cases of CTLA4 antibody-induced colitis reported after HD IL-2 treatment and a CTLA4 antibody induced colitis related death. CONCLUSION: In this retrospective analysis HD IL-2 therapy displayed antitumor activity in melanoma patients who progressed following treatment with ipilimumab. Most HD IL-2 toxicity was not worsened by prior ipilimumab therapy except for one treatment related death from colitis. Care should be taken to avoid reactivation of CTLA4 antibody-induced colitis. PMID- 27660708 TI - Re-discovering NK cell allo-reactivity in the therapy of solid tumors. PMID- 27660709 TI - A case report of Grover's disease from immunotherapy-a skin toxicity induced by inhibition of CTLA-4 but not PD-1. AB - BACKGROUND: Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover's disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab. CASE PRESENTATION: We report an additional case of ipilimumab-induced Grover's disease. Interestingly, this dermatologic side effect did not appear with use of anti-PD-1 therapy in our patient. Immune analysis was performed and suggests a possible role of Th2 cells in its patholgenesis. CONCLUSION: This case suggests that Grover's disease is an irAE induced by Ipilimumab. Our immune analysis suggests that Th2 cells may be pathogenic mediators which warrants further study. PMID- 27660711 TI - Biomarkers immune monitoring technology primer: Immunoscore(r) Colon. PMID- 27660712 TI - Increased FDG avidity in lymphoid tissue associated with response to combined immune checkpoint blockade. AB - BACKGROUND: Antibodies against programmed death 1 (PD-1) receptor and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have transformed the systemic treatment of melanoma and many other cancers. Understanding the spectrum of benign findings and atypical response patterns seen in immune checkpoint blockade is important for accurately assessing treatment response as these immunotherapies become more widely used. CASE PRESENTATION: We report a 63-year-old man with metastatic melanoma successfully treated with combination CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), after non-response to pembrolizumab monotherapy. The initial impression of disease progression, based on cutaneous and PET/CT findings of increased fluoro-2-deoxy-D-glucose (FDG) uptake in benign lymphoid tissue, proved to be erroneous after assiduous review of radiographic imaging and correlative pathology. CONCLUSIONS: These findings indicate that increased FDG uptake in benign lymphoid tissue seen on PET/CT may be a surrogate marker of immune activation and treatment response. Prospective studies will be invaluable in validating immune-related radiographic findings as a prognostic biomarker of response in cancer patients being treated with immune checkpoint blockade. PMID- 27660710 TI - Adjuvants for peptide-based cancer vaccines. AB - Cancer therapies based on T cells have shown impressive clinical benefit. In particular, immune checkpoint blockade therapies with anti-CTLA-4 and anti-PD 1/PD-L1 are causing dramatic tumor shrinkage and prolonged patient survival in a variety of cancers. However, many patients do not benefit, possibly due to insufficient spontaneous T cell reactivity against their tumors and/or lacking immune cell infiltration to tumor site. Such tumor-specific T cell responses could be induced through anti-cancer vaccination; but despite great success in animal models, only a few of many cancer vaccine trials have demonstrated robust clinical benefit. One reason for this difference may be the use of potent, effective vaccine adjuvants in animal models, vs. the use of safe, but very weak, vaccine adjuvants in clinical trials. As vaccine adjuvants dictate the type and magnitude of the T cell response after vaccination, it is critical to understand how they work to design safe, but also effective, cancer vaccines for clinical use. Here we discuss current insights into the mechanism of action and practical application of vaccine adjuvants, with a focus on peptide-based cancer vaccines. PMID- 27660713 TI - Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents. AB - A series of coordination gold(III), palladium(II), and platinum(II) complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline [Ph3P=N C9H6N] (1), have been synthesized and structurally characterized. The coordination palladium(II) and platinum(II) compounds can evolve further, under appropriate conditions, to give stable cyclometalated endo species [M{kappa3 C,N,N-C6H4(PPh2=N-8-C9H6N}Cl] (M = Pd, Pt) by C-H activation of the phenyl group of the PPh 3 fragment. Iminophosphorane 1 and the new metallic complexes are luminescent in DMSO or DMSO:H2O (1:1 mixture) solutions at RT. The compounds have been evaluated for their antiproliferative properties in a human ovarian cancer cell line (A2780S), in human lung cancer cells (A-549) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). Most compounds have been more toxic to the ovarian cancer cell line than to the non-tumorigenic cell line. The new complexes interact with human serum albumin (HSA) faster than cisplatin. Studies of the interactions of the compounds with DNA indicate that, in some cases, they exert anticancer effects in vitro based on different mechanisms of action with respect to cisplatin. PMID- 27660714 TI - Noncontiguous finished genome sequence and description of Murdochiella massiliensis strain SIT12 sp. nov. AB - Murdochiella massiliensis strain SIT12 (= CSUR P1987 = DSM 29078) is the type strain of M. massiliensis sp. nov. This bacterium was isolated from the stool of a healthy 2-year-old Senegalese boy. M. massiliensis is an anaerobic, Gram positive coccus. The genome size of M. massiliensis strain SIT12 is 1 642 295 bp with 48.9% G+C content and assembled into two scaffolds. PMID- 27660715 TI - Night shift work and inflammatory markers in male workers aged 20-39 in a display manufacturing company. AB - BACKGROUND: This study aimed to determine the association between shift work and inflammatory markers, which are independent risk factors of cardiovascular diseases, in male manual workers at a display manufacturing company. METHODS: This study was conducted between June 1 and July 31, 2015 on 244 male manual workers aged 20-39 years old at a display manufacturing company and investigated age, marital status, education level, alcohol consumption habit, smoking habit, regular exercise habit, sleep duration, sleep debt, sleep insufficiency, past medical history, current and past shift work experience, duration of shift work, and weekly work hours through face-to-face interviews using structured questionnaires and performed blood tests. Study participants were divided into daytime, former shift, and current shift workers based on the work schedule. Chi square tests and one-way analyses of variance were performed to compare inflammatory markers and cardiovascular disease risk factors, and analyses of covariance were conducted after adjusting for variables potentially affecting inflammatory markers. RESULTS: High-sensitivity C-reactive protein (hs-CRP; mean +/- standard deviation) levels in daytime, former shift, and current shift workers were 0.65 +/- 0.43, 0.75 +/- 0.43, and 0.86 +/- 0.72 mg/L, respectively (p = 0.029). The leukocyte count (mean +/- standard deviation) was 5,556 +/- 1,123, 6,210 +/- 1,366, and 6,530 +/- 1,216 cells/MUL, respectively (p < 0.001). Both hs-CRP level and leukocyte count were significantly higher in current shift workers than in daytime workers, and leukocyte count was higher in former shift workers than in daytime workers. After adjusting for variables potentially affecting inflammatory markers, hs-CRP levels (adjusted mean +/- standard deviation) in daytime and current shift workers were 0.59 +/- 0.06 and 0.92 +/- 0.07 mg/L, respectively (p = 0.002). The leukocyte count (adjusted mean +/- standard deviation) was 5,557 +/- 124 and 6,498 +/- 144 cells/MUL, respectively (p < 0.001). CONCLUSIONS: A significant association between shift work and increases in inflammatory markers was confirmed. Because chronic low-grade inflammation plays an important role in the development of cardiovascular diseases, regular follow-up of inflammatory markers as a marker of cardiovascular diseases in shift workers may serve as an early indicator in predicting the effects of shift work on health. PMID- 27660716 TI - Association between second-hand smoke and psychological well-being amongst non smoking wageworkers in Republic of Korea. AB - BACKGROUND: Worldwide, exposure to second-hand smoke (SHS) has been responsible for more than 0.6 million deaths and 10.9 million disability-adjusted life years (DALYS) lost in never smokers in 2004. The world health organization (WHO) reported smoking-related death of 58,000 per year in South Korea. There is recent emerging evidence of the associations of SHS exposure with anxiety or depression and poor mental health. Although exposure to second-hand smoke (SHS) has been associated with various physical health conditions and mental health, we are unaware of any studies examining its association with psychological well-being as mental factor. This study aimed to investigate the association between self reported exposure to SHS and well-being among non-smoking wageworkers. METHODS: The Third Korean Working Conditions Survey (KWCS, 2011) was conducted on a representative sample of economically active population aged 15 years or over, who were either employees or self-employed at the time of interview. In this study, after removing inconsistent data, 19,879 non-smoking wageworkers among 60,054 workers were participated. Psychological well-being was measured through the WHO-Five Well-Being Index (1998 version). Univariate and multiple logistic regression models were used to examine the association of SHS exposure with psychological well-being. RESULTS: The unadjusted OR of poor psychological well being (OR: 1.594, 95 % CI: 1.421-1.787) was significantly higher for SHS exposure group compared to non-exposure group. Multiple logistic regression analysis results indicated that these relationships were still significant after adjusting for potential confounders (adjusted OR: 1.330, 95 % CI: 1.178-1.502). CONCLUSIONS: Exposure to SHS was associated with poor well-being measured by the WHO-5 well-being index, indicating the importance of reducing SHS exposure at the workplace for psychological well-being amongst non-smoking wageworkers. PMID- 27660718 TI - Logistic regression analysis on the determinants of stillbirth in Ethiopia. AB - BACKGROUND: Stillbirth is often defined as fetal death after 24 weeks of gestation, but a fetus greater than any combination of 16, 20, 22, 24, or 28 weeks gestational age and 350 g, 400 g, 500 g, or 1000 g birth weight may be considered stillborn depending on local law. Once the fetus has died, the mother may or may not have contractions and undergo childbirth or in some cases, a Caesarean section. Most stillbirths occur in full-term pregnancies. METHODS: This study has intended to model determinants of experiencing stillbirth among women in child bearing age group of Ethiopia using the Ethiopian demographic and health Survey data (EDHS, 2011). First, the bivariate chi-square test of association was fitted to the data and significant variables were considered for further investigation binary logistic regression models were fitted. RESULTS: This study revealed that the rate of experiencing stillbirth among women of child bearing age was about 25.5 per 1000 deliveries in Ethiopia. From binary logistic regression, region of residence, maternal age, place of residence, education level, parity, antenatal care utilization, place of delivery, body mass index (BMI) and anemia level were found to be significantly associated with experiencing stillbirth. CONCLUSIONS: Researchers should use multilevel models than traditional regression methods when their data structure is hierarchical as like in Ethiopian Demographic and Health Survey data. PMID- 27660717 TI - Gender differences in Reasons for Sickness Presenteeism - a study among GPs in a Swedish health care organization. AB - BACKGROUND: It is common that physicians go to work while sick and therefore it is important to understand the reasons behind. Previous research has shown that women and men differ in health and health related behavior. In this study, we examine gender differences among general practitioners who work while sick. METHODS: General practitioners (GP's) working in outpatient care in a Swedish city participated in the study (n = 283; women = 63 %; response rate = 41 %). Data were obtained from a large web-based questionnaire about health and organization within primary care. Two questions about sickness presenteeism (going to work while sick) were included; life-long and during the past 12 months, and five questions about reasons. We controlled for general health, work family conflict and demographic variables. RESULTS: Female physicians reported sickness presenteeism more often than male physicians. Work-family conflict mediated the association between gender and sickness presenteeism. Women reported reasons related with "concern for others" and "workload" more strongly than men. Men reported reasons related with "capacity" and "money" more strongly than women. These differences are likely effects of gender stereotyping and different family-responsibilities. CONCLUSIONS: Gender socialization and gender stereotypes may influence work and health-related behavior. Because sickness presenteeism is related with negative effects both on individuals and at organizational levels, it is important that managers of health organizations understand the reasons for this, and how gender roles may influence the prevalence of sickness presenteeism and the reasons that female and male GPs give for their behavior. PMID- 27660719 TI - Evaluation of feed value of a by-product of pickled radish for ruminants: analyses of nutrient composition, storage stability, and in vitro ruminal fermentation. AB - BACKGROUND: By-products of pickled radish (BPR) are considered food waste. Approximately 300 g/kg of the total mass of raw materials becomes BPR. Production of pickled radish has grown continuously and is presently about 40,000 metric tons annually in Korea. The objective of the present study was thus to explore the possibility of using BPR as a ruminant feed ingredient. RESULTS: BPR contained a large amount of moisture (more than 800 g/kg) and ash, and comprised mostly sodium (103 g/kg DM) and chloride (142 g/kg DM). On a dry matter basis, the crude protein (CP) and ether extract (EE) levels in BPR were 75 g/kg and 7 g/kg, respectively. The total digestible nutrient (TDN) level was 527 g/kg and the major portion of digestible nutrients was carbohydrate; 88 % organic matter (OM) was carbohydrate and 65 % of total carbohydrate was soluble or degradable fiber. The coefficient of variation (CV) of nutrient contents among production batches ranged from 4.65 to 33.83 %. The smallest CV was observed in OM, and the largest, in EE. The variation in CP content was relatively small (10.11 %). The storage stability test revealed that storage of BPR at 20 degrees C (room temperature) might not cause spoilage for 4 d, and possibly longer. If BPR is refrigerated, spoilage can be deferred for 21 d and longer. The in vitro ruminal fermentation study showed that substitution of annual ryegrass straw with BPR improved ruminal fermentation, as evidenced by an increase in VFA concentration, DM degradability, and total gas production. CONCLUSION: The major portion of nutrients in BPR is soluble or degradable fiber that can be easily fermented in the rumen without adverse effects, to provide energy to ruminant animals. Although its high sodium chloride content needs to be considered when formulating a ration, BPR can be successfully used as a feed ingredient in a ruminant diet, particularly if it is one component of a total mixed ration. PMID- 27660720 TI - Coexistence of a Ghon Complex, Pott's Disease, and Hip Arthritis in a Child. AB - INTRODUCTION: Tuberculosis remains a major public health problem in developing countries. Diagnosing extrapulmonary tuberculosis can be difficult, as it requires a higher index of suspicion than primary tuberculosis. Extrapulmonary tuberculosis may mimic malignancies and many other diseases, so it should be included in the differential diagnosis. Here, we present a case of extrapulmonary tuberculosis associated with Pott's disease and hip arthritis in a patient who recovered after 12 months of antituberculosis therapy. CASE PRESENTATION: A 16 year-old girl presented to the outpatient otolaryngology clinic with painless swelling of the neck, and to the physical medicine and rehabilitation clinic with complaints of hip and low back pain that mimicked spondyloarthropathy. She was eventually referred to the outpatient pediatric clinic. Her acute-phase reactants were high, and hilar lymphadenopathy was evident on chest x-ray. On computerized tomography, a Pott's abscess involving the T8, T9, and T10 vertebrae was suspected. Magnetic resonance imaging of the dorsal vertebrae and hip was performed, and a Pott's abscess and hip tuberculous arthritis were confirmed. The patient had been exposed to tuberculosis 10 years earlier, and her purified protein derivative (PPD) test was 16 mm. After antituberculosis treatment, our patient recovered and the Pott's disease and hip tuberculous arthritis regressed. CONCLUSIONS: Extrapulmonary tuberculosis may mimic many other diseases, so it should be kept in mind in the differential diagnosis. It is essential to diagnose osteoarticular tuberculosis early, as late diagnosis or inadequate treatment may cause permanent disability. PMID- 27660721 TI - Comparison Between the Cassia Fistula's Emulsion With Polyethylene Glycol (PEG4000) in the Pediatric Functional Constipation: A Randomized Clinical Trial. AB - BACKGROUND: There are few effective drugs for pediatric functional constipation (FC). OBJECTIVES: Comparing the effectiveness of Cassia fistula's emulsion (CFE) with Polyethylene glycol (PEG4000) in FC; and evaluation of safety of both drugs in the treatment of FC. MATERIALS AND METHODS: A randomized open label, prospective, controlled, parallel-group clinical trial was carried on 109 children (M/F: 63/46; mean age +/- SD: 59.7 +/- 28.8 months) in Amirkola children's hospital, Babol, Iran. The inclusion criteria were based on diagnosis of FC according to the Rome III criteria and age range between 2 - 15 years. They received CFE or PEG randomly for 4 weeks. Frequencies of defecation, severity of pain, consistency of stool, fecal incontinence and retentive posturing were compared between the two groups and with baselines. Children were counted as improved when they exited from Rome III criteria of FC. RESULTS: Fifty seven patients were assigned to receive PEG and 52 patients received CFE. After 4weeks of medication, 86.5% of children in CFE group and 77.1% in PEG group (RR = 1.121, CI95%:0.939 - 1.338) exited from the criteria of FC. All measurable criteria improved in both groups without any significant difference, except in the frequency of defecation that in CFE group (10.96 +/- 5.7) was significantly more than PEG group (6.9 +/- 3.5) (P < 0.0001). Compliances of PEG were significantly better in the 2 first weeks (P = 0.002, 0.008) but not in third and fourth week (P = 0.061, 0.062). None of these two drugs cause clinically significant side effects. CONCLUSIONS: CFE can be as effective as PEG in the 4-weeks treatment of children with FC. PMID- 27660722 TI - Evaluation of the Immunogenicity of Diphtheria Toxoid Conjugated to Salmonella Typhimurium-Derived OPS in a Mouse Model: A Potential Vaccine Candidate Against Salmonellosis. AB - BACKGROUND: Salmonella enterica serovar Typhimurium (S. Typhimurium) causes gastroenteritis in humans and paratyphoid disease in some animals. Given the emergence of antibiotic resistance, vaccines are more effective than chemotherapy in disease control. OBJECTIVES: The aim of this experimental study was to evaluate the immunogenicity of diphtheria toxoid (DT) conjugated with S. Typhimurium -derived OPS (O side chain isolation) in mice to determine its potential as a vaccine candidate against salmonellosis. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was extracted from the bacterial strain. After isolation of the O side chain of LPS, detoxification, and conjugation of the detoxified OPS samples with DT, pyrogenicity, toxicity, and sterility tests were performed. To vaccination, four groups of female Balb/c mice were used in an immunization test. Antibody responses were measured by the ELISA method. Challenging processes were performed to analyze the efficacy of the OPS-DT compound. RESULTS: Two weeks after the first vaccination dose, there was no significant difference in the antibody titers of the OPS and OPS-DT groups. However, after the second and third doses, the antibody titers of the OPS-DT group increased significantly compared with those of the control groups (P < 0.001). The induction of anti-OPS antibodies was as follows: OPS-DT>OPS. The most anti-OPS IgG antibody was IgG1. Challenging procedure showed successful protective characteristics in clinical examinations. CONCLUSIONS: The results indicated that DT increased anti-OPS antibodies against the OPS-DT compound. The antibody response to OPS-DT was greater than that to OPS alone. We conclude that OPS-DT is an appropriate and acceptable vaccine candidate against salmonellosis. PMID- 27660723 TI - Application of Autologous Platelet-Rich Plasma (PRP) on Wound Healing After Caesarean Section in High-Risk Patients. AB - BACKGROUND: Platelet-rich plasma (PRP) is a human plasma product enriched by platelets, growth factors, and fibrinogen with high hemostatic and healing properties. OBJECTIVES: The aim of this study was to evaluate the effect of autologous PRP on wound healing in high-risk women undergoing cesarean sections. PATIENTS AND METHODS: In this balanced, randomized, and controlled trial, 140 patients were admitted to Arash women's hospital, Tehran, Iran from May of 2013 to November of 2014 for elective cesarean surgery. The patients were randomly assigned into two groups. The intervention group received PRP after surgery, whereas the control group received the usual care. All patients were evaluated at baseline, five days, and eight weeks after the cesarean section. The primary endpoint used the REEDA scale for assessing the changes in wound healing. The secondary outcome measures used were the Vancouver scar scale (VSS) and the visual analog scale (VAS). All scale scores were analyzed using a repeated measures test for variance. RESULTS: At the end of study, the PRP group showed a greater reduction in the edema ecchymosed discharge approximation (REEDA) score compared to the control group (85.5% reduction in the PRP group; 72% in the control group) (P < 0.001). Compared with the control group, the PRP group had a significantly greater reduction in the VAN score, beginning on the fifth day after the cesarean section (-0.7, 38% reduction in PRP group; -0.8, 33% in control group) (P < 0.001), and this trend was stable at the end of the eighth week (-0.6, 54% reduction in PRP group; -0.3, 18% in control group). Furthermore, patients treated with PRP experienced a 93% reduction in the VAS score at the end of follow-up, but the control group only observed a 79% reduction (P < 0.001). CONCLUSIONS: It seems that applying PRP is an effective therapeutic approach for wound healing, and faster wound healing is expected due to the presence of more platelets and growth factors. PMID- 27660724 TI - Improved bioavailability of timolol maleate via transdermal transfersomal gel: Statistical optimization, characterization, and pharmacokinetic assessment. AB - Timolol maleate (TiM), a nonselective beta-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from extensive first pass effect, resulting in a reduction of oral bioavailability (F%) to 50% and a short elimination half-life of 4 h; parameters necessitating its frequent administration. The current study was therefore, designed to formulate and optimize the transfersomal TiM gel for transdermal delivery. TiM loaded transfersomal gel was optimized using two 2(3) full factorial designs; where the effects of egg phosphatidyl choline (PC): surfactant (SAA) molar ratio, solvent volumetric ratio, and the drug amount were evaluated. The formulation variables; including particle size, drug entrapment efficiency (%EE), and release rate were characterized. The optimized transfersomal gel was prepared with 4.65:1 PC:SAA molar ratio, 3:1 solvent volumetric ratio, and 13 mg drug amount with particle size of 2.722 MUm, %EE of 39.96%, and a release rate of 134.49 MUg/cm(2)/h. The permeation rate of the optimized formulation through the rat skin was excellent (151.53 MUg/cm(2)/h) and showed four times increase in relative bioavailability with prolonged plasma profile up to 72 h compared with oral aqueous solution. In conclusion, a potential transfersomal transdermal system was successfully developed and the factorial design was found to be a smart tool, when optimized. PMID- 27660725 TI - Optimization of Urea Based Protein Extraction from Formalin-Fixed Paraffin Embedded Tissue for Shotgun Proteomics. AB - Urea based protein extraction of formalin-fixed paraffin-embedded (FFPE) tissue provides the most efficient workflow for proteomics due to its compatibility with liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI MS/MS). This study optimizes the use of urea for proteomic analysis of clinical FFPE tissue. A series of protein extraction conditions manipulating temperature and buffer composition were compared to reduce carbamylation introduced by urea and increase protein detection. Each extraction was performed on a randomized pair of serial sections of homogenous FFPE tissue and analyzed with LC-ESI-MS/MS. Results were compared in terms of yield, missed cleavages, and peptide carbamylation. Lowering extraction temperature to 60 degrees C decreased carbamylation at the cost of decreased protein detection and yield. Protein extraction for at least 20 minutes at 95 degrees C followed by 60 degrees C for 2 hours maximized total protein yield while maintaining protein detection and reducing carbamylation by 7.9%. When accounting for carbamylation during analysis, this modified extraction temperature provides equivalent peptide and protein detection relative to the commercially available Qproteome(r) FFPE Tissue Kit. No changes to buffer composition containing 7 M urea, 2 M thiourea, and 1 M ammonium bicarbonate resulted in improvements to control conditions. Optimized urea in-solution digestion provides an efficient workflow with maximized yields for proteomic analysis of clinically relevant FFPE tissue. PMID- 27660726 TI - Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment. AB - Purpose. The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX ALG nanoparticles were first synthesized by nanoemulsification polymer cross linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients. PMID- 27660727 TI - Characteristics and Trends in Hypnotics Consumption in the Largest Health Care System in Israel. AB - Objectives. To quantify and characterize hypnotics consumption habits among adult patients insured by Clalit Health Services (CHS), the largest health care provider in Israel, in 2000 and 2010. Methods. A retrospective analysis of CHS computerized pharmacy records. Data were collected for all patients over the age of 18 years who were prescribed hypnotics in 2000 and in 2010. Results. Sleep medications were consumed by 8.7% of the adult CHS population in 2000 and by 9.6% in 2010. About one-quarter of consumers were treated for more than 6 months in both years. Multiple sleeping drugs were consumed more often in 2010 (45.2%) than a decade before (22%). While in 2000 benzodiazepines accounted for 84.5% of hypnotics, in 2010 this was reduced to 73.7% (p < 0.05). Of all patients treated for longer than 6 months only 11% in 2000 and 9% in 2010 required a dose escalation suggesting the absence of tolerance. Conclusions. Nine percent of the Israeli population consumes hypnotics. There is a major increase in prescription of combination of medications between 2000 and 2010, with an increase in Z class medications use and reduction in benzodiazepines. Most patients chronically treated did not escalate dosage, suggesting the absence of tolerance. PMID- 27660728 TI - Luteoma of Pregnancy Presenting with Severe Maternal Virilisation: A Case Report. AB - Luteoma of pregnancy is a rare, benign condition characterized by a tumor-like mass of the ovary that emerges during pregnancy and regresses spontaneously after delivery. It is usually asymptomatic and the diagnosis is generally incidental. Luteoma arises from the proliferation of luteinised cell under the influence of beta-hCG and can be hormonally active, with production of androgens resulting in maternal and fetal hirsutism and virilisation. We report a case of a 25-year-old primigravida who presented at 28 weeks of gestation with virilisation symptoms. Serum androgen levels were seven-hundred-fold higher than normal. A diagnosis of pregnancy luteoma was made at the time of caesarean section. The ovarian mass, serum androgen levels, and the condition of the patient improved after delivery. PMID- 27660729 TI - Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor. AB - Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID- 27660730 TI - The Application of Vacuum-Assisted Closure Device in the Management of Empyema Necessitans. AB - Vacuum-assisted closure (VAC) is gaining popularity in the management of many types of acute and chronic wounds. The use of VAC devices in thoracic surgery is limited, but it appears to be promising in complex cases of empyema thoraces. We report a case of empyema necessitans, in which VAC was used to achieve complete wound healing after open drainage which was communicating with the pleural space. PMID- 27660731 TI - Traumatic Rupture of A Posterior Mediastinal Teratoma following Motor-Vehicle Accident. AB - We report a case of a posterior mediastinal mature cystic teratoma with rupture secondary to blunt chest trauma in a 20-year-old male involved in a motor-vehicle accident. Initial treatment was guided by Advanced Trauma Life Support and a tube thoracostomy was performed for presumed hemothorax. The heterogeneous collection within the thoracic cavity was discovered to be the result of a ruptured cystic mass. Pathologic findings confirmed the mass consistent with a mature cystic teratoma. As mediastinal teratomas are most commonly described arising from the anterior mediastinum, the posterior location of the teratoma described in this report is exceedingly rare. PMID- 27660733 TI - Utility of a Dengue-Derived Monoclonal Antibody to Enhance Zika Infection In Vitro. AB - INTRODUCTION: Zika virus (ZIKV) has emerged in dengue (DENV) endemic areas, where these two related flaviviruses continue to co-circulate. DENV is a complex of four serotypes and infections can progress to severe disease. It is thought that this is mediated by antibody dependent enhancement (ADE) whereby antibodies from a primary DENV infection are incapable of neutralizing heterologous DENV infections with another serotype. ADE has been demonstrated among other members of the Flavivirus group. METHODS: We utilize an in vitro ADE assay developed for DENV to determine whether ZIKV is enhanced by a commonly available DENV serotype 2-derived monoclonal antibody (4G2). RESULTS: We show that ZIKV infection in vitro is enhanced in the presence of the 4G2 mAb. DISCUSSION: Our results demonstrate that ADE between ZIKV and DENV is possible and that the 4G2 antibody is a useful tool for the effects of pre-existing anti-DENV antibodies during ZIKV infections. PMID- 27660732 TI - Highly Efficient and Selective Hydrogenation of Aldehydes: A Well-Defined Fe(II) Catalyst Exhibits Noble-Metal Activity. AB - The synthesis and application of [Fe(PNPMe-iPr)(CO)(H)(Br)] and [Fe(PNPMe iPr)(H)2(CO)] as catalysts for the homogeneous hydrogenation of aldehydes is described. These systems were found to be among the most efficient catalysts for this process reported to date and constitute rare examples of a catalytic process which allows selective reduction of aldehydes in the presence of ketones and other reducible functionalities. In some cases, TONs and TOFs of up to 80000 and 20000 h-1, respectively, were reached. On the basis of stoichiometric experiments and computational studies, a mechanism which proceeds via a trans-dihydride intermediate is proposed. The structure of the hydride complexes was also confirmed by X-ray crystallography. PMID- 27660734 TI - Assessment of Prevalence, Beliefs, and Habits of Hookah Smoking Among People with a Medical Background Compared to People with a Non-medical Background: A Cross sectional Self-administered Questionnaire-based Study. AB - INTRODUCTION: Hookah smoking has seen a reemergence in popularity in the last 30 years, particularly in the young urban population. This study aimed to compare the prevalence of and the attitude and beliefs about hookah smoking of people with a medical background and compare it with people from a non-medical background. MATERIALS AND METHODS: An anonymous questionnaire with ten questions about various aspects of hookah smoking was formulated using Google forms(r), which was then circulated via Facebook(r), Whatsapp(r) and emails to the intended participants and all responses were recorded and analyzed. RESULTS: The total number of respondents were 470. The number of respondents with a medical background was 45.31%. The percentage of the respondents with a medical background who smoked a hookah was 28.63%, while the same percentage of the respondents with a non-medical background was 63.42. The perception of hookah being less harmful than a cigarette was not found to be statistically different between the two groups. Respondents with a medical background were more ignorant of the presence or absence of tobacco in the hookah they smoked. The average duration of the hookah smoking habit, the frequency of its use per month, and the average lengths of the hookah smoking session were 3.52 years (95% CI of 3.21 to 3.82), 1.946 (95% CI 1.799 to 2.093), and 58.90 minutes (95% CI of 54.42 to 63.37), respectively. CONCLUSION: The knowledge about the ill effects of smokeless tobacco should be integrated into the structured teaching curriculum of undergraduate medical and dental courses as they prepare future physicians and dental surgeons for an anti-tobacco campaign. PMID- 27660735 TI - A Pilot Study for Evaluation of Digital Systems as an Adjunct to Sphygmomanometry for Undergraduate Teaching. AB - OBJECTIVES: Blood pressure estimation is a key skill for medical practitioners. It is routinely taught to undergraduate medical students using an aneroid sphygmomanometer. However, the conceptual understanding in the practical remains limited. We conducted the following study to evaluate the efficacy of digital data acquisition systems as an adjunct to the sphygmomanometer to teach blood pressure. METHODS: Fifty-seven first-year medical students participated in the study. An MCQ test of 15 questions, consisting of 10 conceptual and five factual questions, was administered twice - pre- and post-demonstration of blood pressure measurement using a digital data acquisition system. In addition, qualitative feedback was also obtained. RESULTS: Median scores were 7 (6 - 8) and 3 (1.5 - 4) in pre-test sessions for conceptual and factual questions, respectively. Post test scores showed a significant improvement in both categories (10 (9 - 10) and 4 (4 - 4.5), respectively, Mann-Whitney U test, p < 0.0001). Student feedback also indicated that the digital system enhanced learning and student participation. CONCLUSIONS: Student feedback regarding the demonstrations was uniformly positive, which was also reflected in significantly improved post-test scores. We conclude that parallel demonstration on digital systems and the sphygmomanometer will enhance student engagement and understanding of blood pressure measurement. PMID- 27660736 TI - Renal Cell Carcinoma Metastasized to Pagetic Bone. AB - Paget's disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget's disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget's disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget's disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget's disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget's disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone. PMID- 27660737 TI - Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging Post-robotic Radiosurgical Pulmonary Vein Isolation (RRPVI): First Case in the World. AB - Pulmonary vein isolation using robotic radiosurgery system CyberKnife is a new non-invasive treatment of atrial fibrillation, currently in clinical phase. Robotic radiosurgical pulmonary vein isolation (RRPVI) uses stereotactic, non invasive (painless) pinpoint radiation energy delivery to a small, precise area to accomplish ablation. The purpose of this report is to describe the finding of an increase in the enhancement of the left atrium demonstrated with the use of cardiac magnetic resonance imaging using late gadolinium enhancement (LGE-CMR) as a result of RRPVI in the first case in the world in humans using CyberKnife as a treatment for paroxysmal atrial fibrillation (PAF). PMID- 27660738 TI - Influence of ice thickness and surface properties on light transmission through Arctic sea ice. AB - The observed changes in physical properties of sea ice such as decreased thickness and increased melt pond cover severely impact the energy budget of Arctic sea ice. Increased light transmission leads to increased deposition of solar energy in the upper ocean and thus plays a crucial role for amount and timing of sea-ice-melt and under-ice primary production. Recent developments in underwater technology provide new opportunities to study light transmission below the largely inaccessible underside of sea ice. We measured spectral under-ice radiance and irradiance using the new Nereid Under-Ice (NUI) underwater robotic vehicle, during a cruise of the R/V Polarstern to 83 degrees N 6 degrees W in the Arctic Ocean in July 2014. NUI is a next generation hybrid remotely operated vehicle (H-ROV) designed for both remotely piloted and autonomous surveys underneath land-fast and moving sea ice. Here we present results from one of the first comprehensive scientific dives of NUI employing its interdisciplinary sensor suite. We combine under-ice optical measurements with three dimensional under-ice topography (multibeam sonar) and aerial images of the surface conditions. We investigate the influence of spatially varying ice-thickness and surface properties on the spatial variability of light transmittance during summer. Our results show that surface properties such as melt ponds dominate the spatial distribution of the under-ice light field on small scales (<1000 m2), while sea ice-thickness is the most important predictor for light transmission on larger scales. In addition, we propose the use of an algorithm to obtain histograms of light transmission from distributions of sea ice thickness and surface albedo. PMID- 27660739 TI - Crystallinity Engineering of Hematite Nanorods for High-Efficiency Photoelectrochemical Water Splitting. AB - An effective strategy to overcome the morphology evolution of hematite nanorods under high-temperature activation is presented, via tuning the crystallinity and sintering temperature by substrate modification. It is demonstrated that the as prepared doping-free hematite nanorods with fine nanostructures obtain a significantly higher photocurrent density of 2.12 mA cm-2 at 1.23 V versus RHE, due to effective charge separation and transfer. PMID- 27660740 TI - Design and Fabrication of Microspheres with Hierarchical Internal Structure for Tuning Battery Performance. AB - Microspheres with controlled nano- and macroporosity are fabricated by template assisted spray drying. Increasing the porosity of the particle up to 20% improves the rate performance of the particles as shown experimentally and by electrochemical simulations of particle lithiation. PMID- 27660741 TI - High Electron Mobility Thin-Film Transistors Based on Solution-Processed Semiconducting Metal Oxide Heterojunctions and Quasi-Superlattices. AB - High mobility thin-film transistor technologies that can be implemented using simple and inexpensive fabrication methods are in great demand because of their applicability in a wide range of emerging optoelectronics. Here, a novel concept of thin-film transistors is reported that exploits the enhanced electron transport properties of low-dimensional polycrystalline heterojunctions and quasi superlattices (QSLs) consisting of alternating layers of In2O3, Ga2O3, and ZnO grown by sequential spin casting of different precursors in air at low temperatures (180-200 degrees C). Optimized prototype QSL transistors exhibit band-like transport with electron mobilities approximately a tenfold greater (25 45 cm2 V-1 s-1) than single oxide devices (typically 2-5 cm2 V-1 s-1). Based on temperature-dependent electron transport and capacitance-voltage measurements, it is argued that the enhanced performance arises from the presence of quasi 2D electron gas-like systems formed at the carefully engineered oxide heterointerfaces. The QSL transistor concept proposed here can in principle extend to a range of other oxide material systems and deposition methods (sputtering, atomic layer deposition, spray pyrolysis, roll-to-roll, etc.) and can be seen as an extremely promising technology for application in next generation large area optoelectronics such as ultrahigh definition optical displays and large-area microelectronics where high performance is a key requirement. PMID- 27660742 TI - Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer. AB - Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated. Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS). Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal. Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected. PMID- 27660743 TI - Phenotypic and Cytogenetic Characterization of Mesenchymal Stromal Cells in De Novo Myelodysplastic Syndromes. AB - Bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are vital in hematopoiesis. Whether BM-MSCs alter their characteristics in Myelodysplastic Syndromes (MDS) is still controversial. We characterized MSCs of de novo MDS patients in Sri Lanka who have not been reported previously in the literature. We also analyzed MSCs derived from different MDS subtypes. MSCs were culture expanded, characterized by flow cytometry, and induced towards osteogenic and adipogenic differentiation. Growth properties were determined using growth curves and population doubling times. Karyotyping and FISH were performed on MSCs. Cell morphology, differentiation potential, and CD marker expression of MDS-MSCs of all subtypes were comparable to those of control-MSCs. No significant growth differences were observed between control MSCs and MDS-MSCs of all subtypes (p > 0.05). 31% of MDS-MSCs had chromosomal aberrations (der(3),del(6q),del(7p), loss of chromosomes) whose BM karyotypes were normal. Highest percentage of karyotypic abnormalities was observed in RCMD-MSCs. Patients with abnormal BM karyotypes had no aberrant MSC clones. Results show that in spite of presence of genetically abnormal clones in MDS-MSC populations, in vitro phenotypic and growth characteristics of MSCs in MDS remain unchanged. Further, the occurrence of genetic abnormalities in BM-MSCs in MDS could be considered as an autonomous event from that of their hematopoietic counterparts. PMID- 27660744 TI - Associations between long commutes and subjective health complaints among railway workers in Norway. AB - Commuting is an important aspect of daily life for many employees, but there is little knowledge of how this affects individual commuters' health and well-being. The authors investigated the relationship between commuting and subjective health complaints, using data from a web-based questionnaire. In a sample of 2126 railway employees, 644 (30.3%) had long commute times. A 29-item inventory was used to measure the number and degree of the subjective health complaints. Those who commuted 60 min or more each way were characterized by significantly higher numbers and degrees of subjective health complaints compared with their peers with short commutes. The mean number of complaints was 7.5 among the former group and 6.4 for the latter group (p = 0.009). In a regression model, in which the authors controlled for age, gender, education, self-rated health, and coping, the employees with long commutes reported more complaints than those with short commutes. Significant associations were found between those with long commutes and the number and degree of incidences of self-reported musculoskeletal pain, pseudo-neurologic complaints, and gastrointestinal problems. Commuters who had had long commutes for more than 10 years reported more gastrointestinal and musculoskeletal complaints than those with long commutes for less than 2 years. Also, commuters with long commutes spent less time with their families and leisure activities compared with those with short commutes. The authors conclude that the association between long commute times and higher levels of subjective health complaints should attract the attention of transport planners, employers, and public health policymaker. PMID- 27660745 TI - Pulmonary microlithiasis - A case report. AB - Pulmonary alveolar microlithiasis is a rare diffuse lung disease characterized by widespread sand-like intra-alveolar calcifications (calcospherites composed of calcium and phosphorus). Around 800 cases have been reported in the literature to date. We report here a case of a 35 years old female with prolonged h/o of exertional dyspnoea and mild cough. Clinical examination was mostly normal. Her Chest X-Ray revealed bilateral multiple nodular opacities (sand storm appearance). CT Scan chest showed diffuse micronodular calcifications with septal thickening, compatible with alveolar microlithiasis. Pulmonary function tests showed moderately restrictive lung disease. Bronchoscopic alveolar lavage revealed calcospherites in the alveloli and bronchi confirming the diagnosis of pulmonary alveolar microlithiasis. PMID- 27660746 TI - Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG. AB - We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized. PMID- 27660747 TI - Neonatal presentation of familial glucocorticoid deficiency with a MRAP mutation: A case report. AB - Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder in which the adrenal cortex fails to respond appropriately to stimulation by adrenocorticotropic hormone (ACTH) to produce cortisol. The disease is characterized in laboratory testing by glucocorticoid deficiency and markedly elevated ACTH levels. FGD may present in infancy or early childhood with symptoms related to low cortisol and high ACTH, such as hyperpigmentation, severe hypoglycemia, failure to thrive and recurrent infections. Mutations in the MC2R accessory protein (MRAP) cause FGD types 2, which accounts for approximately 15 20% of FGD cases. Here, we report a female neonate of Chinese Han origin, who presented with noted hyperpigmentation at birth. Laboratory investigations revealed hypocortisolaemia (cortisol < 1.0 MUg/dl) and elevated plasma ACTH (1051 pg/ml). She responded to hydrocortisone treatment. Genetic studies confirmed the diagnosis showing homozygous deletion (c. 106 + 1delG) in intron 3 of MRAP gene, a mutation already reported as responsible for FDG type 2. This mutation can cause complete lack of ACTH response thus explaining the early presentation in this case. Her parents and maternal grandmother were heterozygous for the same mutation. To our knowledge, this is the first Chinese Han patient reported with FGD type 2 due to a known MRAP mutation. PMID- 27660748 TI - The Effect of Pre-Emptive Dexmedetomidine on the Incidence of Post-Thoracotomy Pain Syndrome in Patients Undergoing Coronary Artery Bypass Grafting. AB - BACKGROUND: Post-thoracotomy pain syndrome (PTPS) is pain that recurs or persists along a thoracotomy incision for at least two months following surgery. Dexmedetomidine (dex) is an alpha-2 agonist that also has analgesic, sedative hypnotic, and sympatholytic properties. OBJECTIVES: To determine the effect of pre-emptive dexmedetomidine on the incidence of PTPS in patients undergoing coronary artery bypass grafting (CABG). PATIENTS AND METHODS: This randomized clinical trial enrolled 104 candidates for elective coronary artery bypass grafting (CABG) and randomly assigned them to either a dex group or a control group. In the dex group, dexmedetomidine 0.5 ug/kg/hour was infused from the initiation of anesthesia until postoperative extubation in the intensive-care unit. Two months after surgery, the patients were contacted by telephone and interviewed to determine the presence of pain at the thoracotomy scars. RESULTS: Fifty-four patients were placed in the control group, and 50 patients were assigned to the dex group. The age, sex, and body mass index were not significantly different between the two groups of study (P > 0.05). The incidence of PTPS was 11/50 (22%) patients in the dex group and 28/54 patients (52%) in the control group. A chi-square test revealed a significant difference in the incidence of PTPS after two months between the dex and control groups (P = 0.032). CONCLUSIONS: PTPS is a common problem following CABG, and pre-emptive therapy with dex may decrease neuropathic pain. PMID- 27660749 TI - Oncolytic Seneca Valley Virus: past perspectives and future directions. AB - Seneca Valley Virus isolate 001 (SVV-001) is an oncolytic RNA virus of the Picornaviridae family. It is also the first picornavirus discovered of the novel genus Senecavirus. SVV-001 replicates through an RNA intermediate, bypassing a DNA phase, and is unable to integrate into the host genome. SVV-001 was originally discovered as a contaminant in the cell culture of fetal retinoblasts and has since been identified as a potent oncolytic virus against tumors of neuroendocrine origin. SVV-001 has a number of features that make it an attractive oncolytic virus, namely, its ability to target and penetrate solid tumors via intravenous administration, inability for insertional mutagenesis, and being a self-replicating RNA virus with selective tropism for cancer cells. SVV 001 has been studied in both pediatric and adult early phase studies reporting safety and some clinical efficacy, albeit primarily in adult tumors. This review summarizes the current knowledge of SVV-001 and what its future as an oncolytic virus may hold. PMID- 27660750 TI - VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC. PMID- 27660751 TI - Effect of the Children's Health Activity Motor Program on Motor Skills and Self Regulation in Head Start Preschoolers: An Efficacy Trial. AB - Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children's Health Activity Motor Program, CHAMP) that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 +/- 6.5 months; 49.5% males) were randomly assigned to a treatment (n = 68) or control (n = 45) program. CHAMP participants engaged in 15, 40-min sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development-2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time * treatment interaction (p < 0.001). In regard to motor skills, post hoc comparisons found that all children improved their motor skills (p < 0.05), but the CHAMP group improved significantly more than the control group (p < 0.001). Children in CHAMP maintained their self-regulation scores across time, while children in the control group scored significantly lower than the CHAMP group at the posttest (p < 0.05). CHAMP is a mastery climate movement program that enhance skills associated with healthy development in children (i.e., motor skills and self-regulation). This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool age children and significantly improved motor skills while participating in outdoor recess was not effective. CHAMP could help contribute to children's learning-related skills and physical development and subsequently to their academic success. PMID- 27660753 TI - Adoption of Evidence-Based Fall Prevention Practices in Primary Care for Older Adults with a History of Falls. AB - A multifactorial approach to assess and manage modifiable risk factors is recommended for older adults with a history of falls. Limited research suggests that this approach does not routinely occur in clinical practice, but most related studies are based on provider self-report, with the last chart audit of United States practice published over a decade ago. We conducted a retrospective chart review to assess the extent to which patients aged 65+ years with a history of repeated falls or fall-related health-care use received multifactorial risk assessment and interventions. The setting was an academic primary care clinic in the Pacific Northwest. Among the 116 patients meeting our inclusion criteria, 48% had some type of documented assessment. Their mean age was 79 +/- 8 years; 68% were female, and 10% were non-white. They averaged six primary care visits over a 12-month period subsequent to their index fall. Frequency of assessment of fall risk factors varied from 24% (for home safety) to 78% (for vitamin D). An evidence-based intervention was recommended for identified risk factors 73% of the time, on average. Two risk factors were addressed infrequently: medications (21%) and home safety (24%). Use of a structured visit note template independently predicted assessment of fall-risk factors (p = 0.003). Geriatrics specialists were more likely to use a structured note template (p = 0.04) and perform more fall-risk factor assessments (4.6 vs. 3.6, p = 0.007) than general internists. These results suggest opportunities for improving multifactorial fall risk assessment and management of older adults at high fall risk in primary care. A structured visit note template facilitates assessment. Given that high-risk medications have been found to be independent risk factors for falls, increasing attention to medications should become a key focus of both public health educational efforts and fall prevention in primary care practice. PMID- 27660752 TI - Why Tell Children: A Synthesis of the Global Literature on Reasons for Disclosing or Not Disclosing an HIV Diagnosis to Children 12 and under. AB - While the psychological and health benefits of knowing one's HIV diagnosis have been documented for adults and adolescents, practice is still in development for younger children. Moderating conditions for whether or not to tell a child he/she has HIV vary by region and local context. They include accessibility of treatment, consideration of HIV as a stigmatizing condition, prevalence of HIV, and an accompanying presumption that any illness is HIV-related, parent or caregiver concerns about child reactions, child's worsening health, assumptions about childhood and child readiness to know a diagnosis, and lack of policies such as those that would prevent bullying of affected children in schools. In this systematic review of the global literature, we summarize the reasons caregivers give for telling or not telling children 12 and under their HIV diagnosis. We also include articles in which children reflect on their desires for being told. While a broad number of reasons are given for telling a child - e.g., to aid in prevention, adaptation to illness (e.g., primarily to promote treatment adherence), understanding social reactions, and maintaining the child adult relationship - a narrower range of reasons, often related to immediate child or caregiver well-being or discomfort, are given for not telling. Recommendations are made to improve the context for disclosure by providing supports before, during, and after disclosure and to advance the research agenda by broadening samples and refining approaches. PMID- 27660754 TI - Porcine Milk Oligosaccharides and Sialic Acid Concentrations Vary Throughout Lactation. AB - BACKGROUND: Milk oligosaccharides (OSs) are bioactive components known to influence neonatal development. These compounds have specific physiological functions acting as prebiotics, immune system modulators, and enhancing intestine and brain development. OBJECTIVES: The pig is a commonly used model for studying human nutrition, and there is interest in quantifying OS composition of porcine milk across lactation compared with human milk. In this study, we hypothesized that OS and sialic acid (SA) composition of porcine milk would be influenced by stage of lactation. METHODS: Up to 250 mL of milk were collected from seven sows at each of three time points: day 0 (colostrum), days 7-9 (mature), and days 17 19 (weaning). Colostrum was collected within 6 h of farrowing and 3-day intervals were used for mature and weaning milk to ensure representative sampling. Milk samples were analyzed for OS profiles by Nano-LC Chip-QTOF MS, OS concentrations via HPAEC-PAD, and SA (total and free) was assessed by enzymatic reaction fluorescence detection. RESULTS: Sixty unique OSs were identified in porcine milk. Neutral OSs were the most abundant at each lactation stage (69-81%), followed by acidic-sialylated OSs (16-29%) and neutral-fucosylated OSs (2-4%). As lactation progressed, acidic OSs decreased (P = 0.003), whereas neutral fucosylated (P < 0.001) and neutral OSs (P = 0.003) increased throughout lactation. Six OSs were present in all samples analyzed across lactation [lacto-N difucohexaose I (LNDFH-I), 2'-fucosyllactose (2'-FL), lacto-N-fucopentaose I (LNFP-I), lacto-N-neohexaose (LNnH), alpha1-3,beta-4-d-galactotriose (3-Hex), 3' sialyllactose (3'-SL)], while LDFT was present only in colostrum samples. Analysis of individual OS concentrations indicated differences (P = 0.023) between days 0 and 7. Conversely, between days 7 and 18, OS concentrations remained stable with only LNnH (P < 0.001) and LNDFH-I (P = 0.002) decreasing over this period. Analysis of free SA indicated a decrease (P < 0.001) as lactation progressed, while bound (P < 0.001) and total (P < 0.001) SA increased across lactation. CONCLUSION: Concentrations of OS differ between colostrum and mature milk in the pig, and SA concentrations shift from free to bound forms as lactation progresses. Our results suggest that although porcine milk OS concentration and the number of structures is lower than human milk, the OS profile appears to be closer to human milk rather than to bovine milk, based on previously published profiles. PMID- 27660755 TI - Genome-Wide Characterization and Expression Profiles of the Superoxide Dismutase Gene Family in Gossypium. AB - Superoxide dismutase (SOD) as a group of significant and ubiquitous enzymes plays a critical function in plant growth and development. Previously this gene family has been investigated in Arabidopsis and rice; it has not yet been characterized in cotton. In our study, it was the first time for us to perform a genome-wide analysis of SOD gene family in cotton. Our results showed that 10 genes of SOD gene family were identified in Gossypium arboreum and Gossypium raimondii, including 6 Cu-Zn-SODs, 2 Fe-SODs, and 2 Mn-SODs. The chromosomal distribution analysis revealed that SOD genes are distributed across 7 chromosomes in Gossypium arboreum and 8 chromosomes in Gossypium raimondii. Segmental duplication is predominant duplication event and major contributor for expansion of SOD gene family. Gene structure and protein structure analysis showed that SOD genes have conserved exon/intron arrangement and motif composition. Microarray based expression analysis revealed that SOD genes have important function in abiotic stress. Moreover, the tissue-specific expression profile reveals the functional divergence of SOD genes in different organs development of cotton. Taken together, this study has imparted new insights into the putative functions of SOD gene family in cotton. Findings of the present investigation could help in understanding the role of SOD gene family in various aspects of the life cycle of cotton. PMID- 27660756 TI - Characterization and Prediction of Protein Flexibility Based on Structural Alphabets. AB - Motivation. To assist efforts in determining and exploring the functional properties of proteins, it is desirable to characterize and predict protein flexibilities. Results. In this study, the conformational entropy is used as an indicator of the protein flexibility. We first explore whether the conformational change can capture the protein flexibility. The well-defined decoy structures are converted into one-dimensional series of letters from a structural alphabet. Four different structure alphabets, including the secondary structure in 3-class and 8 class, the PB structure alphabet (16-letter), and the DW structure alphabet (28 letter), are investigated. The conformational entropy is then calculated from the structure alphabet letters. Some of the proteins show high correlation between the conformation entropy and the protein flexibility. We then predict the protein flexibility from basic amino acid sequence. The local structures are predicted by the dual-layer model and the conformational entropy of the predicted class distribution is then calculated. The results show that the conformational entropy is a good indicator of the protein flexibility, but false positives remain a problem. The DW structure alphabet performs the best, which means that more subtle local structures can be captured by large number of structure alphabet letters. Overall this study provides a simple and efficient method for the characterization and prediction of the protein flexibility. PMID- 27660757 TI - DARE Train-the-Trainer Pedagogy Development Using 2-Round Delphi Methodology. AB - The Dispatcher-Assisted first REsponder programme aims to equip the public with skills to perform hands-only cardiopulmonary resuscitation (CPR) and to use an automated external defibrillator (AED). By familiarising them with instructions given by a medical dispatcher during an out-of-hospital cardiac arrest call, they will be prepared and empowered to react in an emergency. We aim to formalise curriculum and standardise the way information is conveyed to the participants. A panel of 20 experts were chosen. Using Delphi methodology, selected issues were classified into open-ended and close-ended questions. Consensus for an item was established at a 70% agreement rate within the panel. Questions that had 60%-69% agreement were edited and sent to the panel for another round of voting. After 2 rounds of voting, 70 consensus statements were agreed upon. These covered the following: focus of CPR; qualities and qualifications of trainers; recognition of agonal breathing; head-tilt-chin lift; landmark for chest compression; performance of CPR when injuries are present; trainers' involvement in training lay people; modesty of female patients during CPR; AED usage; content of trainer's manual; addressing of questions and answers; updates-dissemination to trainers and attendance of refresher courses. Recommendations for pedagogy for trainers of dispatcher-assisted CPR programmes were developed. PMID- 27660758 TI - Failure of Polyethylene Inlays in Cementless Total Hip Arthroplasty: A Retrieval Analysis. AB - A retrieval analysis has been performed on 50 polyethylene inlays of cementless screw ring implants (Mecring, Mecron, Berlin, Germany) to investigate the failure mechanism of this specific open cup hip arthroplasty design that has shown a high clinical failure rate. Design-specific damage modes like rim creep, collar fatigue, and backside wear were assessed. Furthermore, the inlays were measured using a CMM to determine deformation. In 90% backside wear was observed and collar fatigue occurred in 68% of the cases. Rim creep was present in 38% of the polyethylene inlays. In 90% of the cases the cup opening diameter was 32.1 mm or less and 46% had a diameter less than 32 mm. It seems that creep and deformation of the polyethylene leads to a reduced diameter at the cup opening and consequently decreased clearance. To avoid this type of failure, polyethylene inlays should be supported at the back by the cup to reduce the risk of ongoing creep deformation. PMID- 27660759 TI - Role of Long Noncoding RNA HOTAIR in the Growth and Apoptosis of Osteosarcoma Cell MG-63. AB - This study investigated the function of HOTAIR in the growth and apoptosis of OS MG-63 cell line in vitro and further clarified its mechanism. The expression levels of HOTAIR in OS MG-63 cell line and normal osteoblast hFOB1.19 cell line were determined by RT-PCR, respectively. The growth and apoptosis of MG-63 cells in vitro were investigated by MTT assay and flow cytometry assay after HOTAIR was knocked down with retroviral vector construction. And the expression levels of cell growth and apoptosis related factors TGF-beta, p53, Bcl-2, and TNF-alpha were determined to clarify the mechanism. We found that HOTAIR was highly expressed in osteosarcoma MG-63 cell line compared with normal osteoblast hFOB1.19 cell line. The proliferation rate was lower and the apoptosis rate was higher significantly in shHOTAIR MG-63 cells than those in EV MG-63 cells. TGF beta and Bcl-2 were downregulated significantly when HOTAIR was knocked down. p53 and TNF-alpha were upregulated significantly when HOTAIR was knocked down. These results indicated that HOTAIR functioned as a carcinogenic lncRNA, which could promote the proliferation and inhibit the apoptosis of MG-63 cells in vitro. HOTAIR could be a potential target for the treatment of osteosarcoma. PMID- 27660760 TI - Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels. AB - Recent research had shown a correlation between aging and decreasing Gamma aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the "core hub" of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r = -0.523, p = 0.081). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (r = -0.518, p = 0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r = -0.028, p = 0.93). Therefore, age and gray matter/white matter ratio account for different part of R-squared (adjusted R-squared = 0.5187) as independent variables for predicting GABA levels. Adjusted R-squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline. PMID- 27660761 TI - ProFold: Protein Fold Classification with Additional Structural Features and a Novel Ensemble Classifier. AB - Protein fold classification plays an important role in both protein functional analysis and drug design. The number of proteins in PDB is very large, but only a very small part is categorized and stored in the SCOPe database. Therefore, it is necessary to develop an efficient method for protein fold classification. In recent years, a variety of classification methods have been used in many protein fold classification studies. In this study, we propose a novel classification method called proFold. We import protein tertiary structure in the period of feature extraction and employ a novel ensemble strategy in the period of classifier training. Compared with existing similar ensemble classifiers using the same widely used dataset (DD-dataset), proFold achieves 76.2% overall accuracy. Another two commonly used datasets, EDD-dataset and TG-dataset, are also tested, of which the accuracies are 93.2% and 94.3%, higher than the existing methods. ProFold is available to the public as a web-server. PMID- 27660762 TI - Acute Oral Mammalian Toxicity and Effect of Solvents on Efficacy of Maerua edulis (Gilg. & Ben.) De Wolf against Rhipicephalus (Boophilus) decoloratus Koch, 1844 (Acarina: Ixodidae), Tick Larvae. AB - Efficacy and toxicity of aqueous and organic solvents extracts of Maerua edulis against ticks and mice, respectively, were determined. Ground leaves were extracted separately using cold water, cold water plus surfactant (1% v/v liquid soap), hot water plus surfactant, hexane, or methanol to make 25% w/v stock solutions from which serial dilutions of 5, 10, 20, and 25% were made. For each concentration, 20 Rhipicephalus decoloratus tick larvae were put in filter papers impregnated with extracts and incubated for 48 h at 27 degrees C and 85-90% RH for mortality observation after 24 h and 48 h. In the toxicity experiment, hot water plus surfactant treatments of 5, 10, 20, and 25% (w/v) M. edulis were administered in suspension per os to sexually mature Balb/C mice and observed for clinical signs and mortality for 72 h. Larvae mortality was highest (>98%) in methanol-extracted M. edulis treatments (20 and 25%), which was not different from the amitraz-based control (Tickbuster(r)). Mortality was also higher in the hot water than in cold water plus surfactant treatments (P < 0.05). No postadministration adverse health effects were observed in the mice. These results suggest that M. edulis is an effective tick remedy best extracted using methanol or hot water plus surfactant. PMID- 27660764 TI - Immunopathology of Parasitic Infections and Therapeutic Approaches in Humans and Animals. PMID- 27660763 TI - An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms. AB - Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset from Synechococcus elongatus, which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge. PMID- 27660765 TI - Does the Laser-Microtextured Short Implant Collar Design Reduce Marginal Bone Loss in Comparison with a Machined Collar? AB - Purpose. To compare marginal bone loss between subgingivally placed short-collar implants with machined collars and those with machined and laser-microtextured collars. Materials and Methods. The investigators used a retrospective study design and included patients who needed missing posterior teeth replaced with implants. Short-collar implants with identical geometries were divided into two groups: an M group, machined collar; and an L group, machined and laser microtextured collar. Implants were evaluated according to marginal bone loss, implant success, and probing depth (PD) at 3 years of follow-up. Results. Sixty two patients received 103 implants (56 in the M group and 47 in the L group). The cumulative survival rate was 100%. All implants showed clinically acceptable marginal bone loss, although bone resorption was lower in the L group (0.49 mm) than in the M group (1.38 mm) at 3 years (p < 0.01). A significantly shallower PD was found for the implants in the L group during follow-up (p < 0.01). Conclusions. Our results suggest predictable outcomes with regard to bone loss for both groups; however, bone resorption was less in the L group than in the M group before and after loading. The laser-microtextured collar implant may provide a shallower PD than the machined collar implant. PMID- 27660766 TI - The physical and physiological effects of vacuum massage on the different skin layers: a current status of the literature. AB - Vacuum massage is a non-invasive mechanical massage technique performed with a mechanical device that lifts the skin by means of suction, creates a skin fold and mobilises that skin fold. In the late 1970s, this therapy was introduced to treat traumatic or burn scars. Although vacuum massage was invented to treat burns and scars, one can find very little literature on the effects of this intervention. Therefore, the aim of this review is to present an overview of the available literature on the physical and physiological effects of vacuum massage on epidermal and dermal skin structures in order to find the underlying working mechanisms that could benefit the healing of burns and scars. The discussion contains translational analysis of the results and provides recommendations for future research on the topic. An extended search for publications was performed using PubMed, Web of Science and Google Scholar. Two authors independently identified and checked each study against the inclusion criteria. Nineteen articles were included in the qualitative synthesis. The two most reported physical effects of vacuum massage were improvement of the tissue hardness and the elasticity of the skin. Besides physical effects, a variety of physiological effects are reported in literature, for example, an increased number of fibroblasts and collagen fibres accompanied by an alteration of fibroblast phenotype and collagen orientation. Little information was found on the decrease of pain and itch due to vacuum massage. Although vacuum massage initially had been developed for the treatment of burn scars, this literature review found little evidence for the efficacy of this treatment. Variations in duration, amplitude or frequency of the treatment have a substantial influence on collagen restructuring and reorientation, thus implying possible beneficial influences on the healing potential by mechanotransduction pathways. Vacuum massage may release the mechanical tension associated with scar retraction and thus induce apoptosis of myofibroblasts. Suggestions for future research include upscaling the study design, investigating the molecular pathways and dose dependency, comparing effects in different stages of repair, including evolutive parameters and the use of more objective assessment tools. PMID- 27660767 TI - Fetal-Type Variants of the Posterior Cerebral Artery and Concurrent Infarction in the Major Arterial Territories of the Cerebral Hemisphere. AB - Fetal-type or fetal posterior cerebral artery (FPCA) is a variant of cerebrovascular anatomy in which the distal posterior cerebral artery (PCA) territory is perfused by a branch of the internal carotid artery (ICA). In the presence of FPCA, thromboembolism in the anterior circulation may result in paradoxical PCA territory infarction with or without concomitant infarction in the territories of the middle (MCA) or the anterior (ACA) cerebral artery. We describe 2 cases of FPCA and concurrent acute infarction in the PCA and ICA territories-right PCA and MCA in Patient 1 and left PCA, MCA, and ACA in Patient 2. Noninvasive angiography detected a left FPCA in both patients. While FPCA was clearly the mechanism of paradoxical infarction in Patient 2, it turned out to be an incidental finding in Patient 1 when evidence of a classic right PCA was uncovered from an old computed tomography scan image. Differences in anatomical details of the FPCA in each patient suggest that the 2 FPCAs are developmentally different. The FPCA of Patient 1 appeared to be an extension of the embryonic left posterior communicating artery (PcomA). Patient 2 had 2 PCAs on the left (PCA duplication), classic bilateral PCAs, and PcomAs, and absent left anterior choroidal artery (AchoA), suggesting developmental AchoA-to-FPCA transformation on the left. These 2 cases underscore the variable anatomy, clinical significance, and embryological origins of FPCA variants. PMID- 27660768 TI - Draft Genome Sequences of 40 Salmonella enterica Serovar Typhimurium Strains Isolated from Humans and Food in Brazil. AB - Salmonellosis is an important health problem worldwide and Salmonella enterica serovar Typhimurium is one of the most common isolated serovars. Here, we reported the draft genomes of 40 S Typhimurium strains isolated from humans and food in Brazil. These draft genomes will improve phylogenetic analysis and will help enhance our understanding of strains of this serovar isolated in Brazil. PMID- 27660769 TI - Draft Genome Sequence of Stenotrophomonas maltophilia SBo1 Isolated from Bactrocera oleae. AB - Bacteria of the genus Stenotrophomonas are ubiquitous in the environment and are increasingly associated with insects. Stenotrophomonas maltophilia SBo1 was cultured from the gut of Bactrocera oleae The draft genome sequence presented here will inform future investigations into the nature of the interaction between insects and their microbiota. PMID- 27660770 TI - Draft Genome Sequence of Klebsiella pneumoniae Strain AS Isolated from Zhejiang Provincial Hospital of TCM, China. AB - Klebsiella pneumoniae is a Gram-negative, nonmotile, encapsulated, lactose fermenting, facultative anaerobic, rod-shaped bacterium. Here we present draft genome assemblies of Klebsiella pneumoniae AS, which was isolated in China. The genomic information will provide a better understanding of the physiology, adaptation, and evolution of K. pneumoniae. PMID- 27660771 TI - Genome Sequence of Lassa Virus Isolated from the First Domestically Acquired Case in Germany. AB - Lassa virus (LASV) is a zoonotic, hemorrhagic fever-causing virus endemic in West Africa, for which no approved vaccines or specific treatment options exist. Here, we report the genome sequence of LASV isolated from the first case of acquired Lassa fever disease outside of Africa. PMID- 27660772 TI - Draft Genome Sequence of Pseudomonas sp. LAB-08 Isolated from Trichloroethene Contaminated Aquifer Soil. AB - Pseudomonas sp. LAB-08 was isolated from a phenol-fed bioreactor constructed with contaminated aquifer soil as the inoculum. Strain LAB-08 utilized phenol as a sole carbon and energy source. Here, we report the genome sequence and annotation of Pseudomonas sp. LAB-08. PMID- 27660773 TI - Draft Genome Sequences of 11 Salmonella enterica Strains with Variable Levels of Barotolerance. AB - The diversity of the genus Salmonella is reflected in the physiological adaptations used by its members in response to stressors such as high pressure. Here we report the draft whole genome sequences of 11 Salmonella enterica strains, five sensitive strains and six demonstrating high levels of pressure resistance. PMID- 27660774 TI - Draft Genome Sequences of Two Salmonella enterica Strains Isolated from Sprouted Chia and Flax Seed Powders. AB - A 2014 foodborne salmonellosis outbreak in Canada and the United States implicated, for the first time, sprouted chia seed powder as the vehicle of transmission. Here, we report the draft whole genome sequences of two Salmonella enterica strains isolated from sprouted powders related to the aforementioned outbreak. PMID- 27660775 TI - Genome Sequence of the Oral Probiotic Streptococcus salivarius JF. AB - Streptococcus salivarius is a nonpathogenic Gram-positive bacterium and the predominant colonizer of the oral microbiota. It finds a wide application in the prevention of upper respiratory tract infections, also reducing the frequency of other main pathogens. Here, we present the complete genome sequence of the oral probiotic S. salivarius JF. PMID- 27660776 TI - Chloroplast Genome Sequence of Arabidopsis thaliana Accession Landsberg erecta, Assembled from Single-Molecule, Real-Time Sequencing Data. AB - A publicly available data set from Pacific Biosciences was used to create an assembly of the chloroplast genome sequence of the Arabidopsis thaliana genotype Landsberg erecta The assembly is solely based on single-molecule, real-time sequencing data and hence provides high resolution of the two inverted repeat regions typically contained in chloroplast genomes. PMID- 27660777 TI - Genome Sequence of a Novel Multiple-Antibiotic-Resistant Member of the Erysipelotrichaceae Family Isolated from a Swine Manure Storage Pit. AB - The swine gastrointestinal tract and stored swine manure may serve as reservoirs of antibiotic resistance genes, as well as sources of novel bacteria. Here, we report the draft genome sequence of a novel taxon in the Erysipelotrichaceae family, isolated from a swine manure storage pit that is resistant to multiple antibiotics. PMID- 27660778 TI - Draft Genome Sequence of Clostridium sp. Strain W14A Isolated from a Cellulose Degrading Biofilm in a Landfill Leachate Microcosm. AB - Here, we report the draft genome of Clostridium sp. strain W14A, isolated from the anaerobic, cellulolytic biofilm of a cotton string sample incubated in a landfill leachate microcosm. The draft genome comprises 131 contigs, 3,823,510 bp, 51.5% G+C content, and 4,119 predicted coding domain sequences. PMID- 27660779 TI - Draft Genome Sequence of a Klebsiella pneumoniae Strain (New Sequence Type 2357) Carrying Tn3926. AB - We present the draft genome sequence of a Klebsiella pneumoniae carbapenemase producing sequence type 2357 (ST2357) strain, NB60, which contains drug-resistant genes encoding resistance to beta-lactams, fluoroquinolones, aminoglycosides, trimethoprim-sulfamethoxazole, colistin, macrolides, and tetracycline. Strain NB60 was isolated from human blood, making it an important tool for studying K. pneumoniae pathogenesis. PMID- 27660780 TI - Draft Genome Sequence of Plasmopara viticola, the Grapevine Downy Mildew Pathogen. AB - Plasmopara viticola is a biotrophic pathogenic oomycete responsible for grapevine downy mildew. We present here the first draft of the P. viticola genome. Analysis of this sequence will help in understanding plant-pathogen interactions in oomycetes, especially pathogen host specialization and adaptation to host resistance. PMID- 27660781 TI - High-Quality Draft Genome Sequence of the Multidrug-Resistant Clinical Isolate Enterococcus faecium VRE16. AB - Specific lineages of the commensal bacterium Enterococcus faecium belonging to CC17, especially ST412, have been isolated from patients in several hospitals worldwide and harbor antibiotic resistance genes and virulence factors. Here, we report a high-quality draft genome sequence and highlight features of E. faecium VRE16, a representative of this ST. PMID- 27660782 TI - Complete Genome Sequence of Feline Calicivirus Strain GX01-2013 Isolated from Household Cats in Guangxi, Southern China. AB - Here, we report the complete genome of a feline calicivirus (FCV) originating from household cats in Guangxi, southern China, in September 2013. To understand its genetic characteristics, we isolated FCV strain GX01-2013 from MDCK cells and determined its complete genome sequence. PMID- 27660783 TI - Draft Genome Sequence of a Cardiobacterium hominis Strain Isolated from Blood Cultures of a Patient with Infective Endocarditis. AB - Cardiobacterium hominis is a well-known commensal bacterium of the oral cavity and an agent of infective endocarditis in humans. Here, we provide a draft genome sequence of a pathogenic strain isolated from blood cultures of a patient with infectious endocarditis. PMID- 27660784 TI - Draft Genome Sequence of Marine Sponge Symbiont Pseudoalteromonas luteoviolacea IPB1, Isolated from Hilo, Hawaii. AB - We report here the 6.0-Mb draft genome assembly of Pseudoalteromonas luteoviolacea strain IPB1 that was isolated from the Hawaiian marine sponge Iotrochota protea Genome mining complemented with bioassay studies will elucidate secondary metabolite biosynthetic pathways and will help explain the ecological interaction between host sponge and microorganism. PMID- 27660785 TI - Complete Genome Sequence of the Avian Paramyxovirus Serotype 5 Strain APMV 5/budgerigar/Japan/TI/75. AB - Here, we report the complete genome sequence of the avian paramyxovirus serotype 5 strain APMV-5/budgerigar/Japan/TI/75, which was determined using the Illumina MiSeq platform. The determined sequence shares 97% homology and similar genetic features with the previously known genome sequence of avian paramyxovirus serotype 5 strain APMV-5/budgerigar/Japan/Kunitachi/74. PMID- 27660786 TI - Draft Genome Sequences of Histamine- and Non-Histamine-Producing Photobacterium Strains. AB - Histamine-producing bacteria (HPBs) have recently been identified from the marine environment. The identification and characterization of HPBs is important to developing effective mitigation strategies for scombrotoxin fish poisoning. We report here the draft genomes of seven histamine-producing and two non-histamine producing marine Photobacterium strains. PMID- 27660787 TI - Complete Genome Sequences of 17 Rapidly Growing Nontuberculous Mycobacterial Strains. AB - We report the complete genome sequences of 17 rapidly growing nontuberculous mycobacterial (NTM) strains, including 16 Mycobacterium abscessus complex strains and one M. immunogenum strain. These sequences add value to studies of the genetic diversity of rapidly growing NTM strains recovered from human specimens. PMID- 27660788 TI - Complete Genome Sequence of Spiroplasma turonicum Tab4cT, a Bacterium Isolated from Horse Flies (Haematopota sp.). AB - Spiroplasma turonicum Tab4c(T) was isolated from a horse fly (Haematopota sp.; probably Haematopota pluvialis) collected at Champchevrier, Indre-et-Loire, Touraine, France, in 1991. Here, we report the complete genome sequence of this bacterium to facilitate the investigation of its biology and the comparative genomics among Spiroplasma spp. PMID- 27660790 TI - Identification and Whole-Genome Sequencing of Four Enterovirus D68 Strains in Southern China in Late 2015. AB - Four enterovirus D68 (EV-D68) strains from four children with influenza-like illness were identified in Shenzhen, southern China, in late 2015. Here, we announce the availability of these viral genomes in GenBank. The genomic sequences of these EV-D68 strains showed the closest phylogenetic relationship to strains from northern China. PMID- 27660789 TI - Draft Genome Sequence of Heavy Metal-Resistant Cupriavidus alkaliphilus ASC-732T, Isolated from Agave Rhizosphere in the Northeast of Mexico. AB - Cupriavidus alkaliphilus ASC-732(T) was isolated from the rhizosphere of agave plant growing in alkaline soils in San Carlos, Tamaulipas, Mexico. The species is able to grow in the presence of arsenic, zinc, and copper. The genome sequence of strain ASC-732(T) is 6,125,055 bp with 5,586 genes and an average G+C content of 67.81%. PMID- 27660791 TI - Genome Sequence of the Arsenic-Resistant Haladaptatus sp. Strain R4 Isolated from Ramnagar, West Bengal, India. AB - Here, we present the draft genome of Haladaptatus sp. strain R4, a halophilic archaea that produces an orange-pink pigment and is capable of growing in a wide salinity range. The genome assembly shows genes for arsenic resistance, siderophore production, trehalose and glycine betaine biosynthesis, uptake and transporters of sodium, potassium, and chloride ions. PMID- 27660792 TI - Complete Genome Sequence of Streptomyces clavuligerus F613-1, an Industrial Producer of Clavulanic Acid. AB - Streptomyces clavuligerus strain F613-1 is an industrial strain with high-yield clavulanic acid production. In this study, the complete genome sequence of S. clavuligerus strain F613-1 was determined, including one linear chromosome and one linear plasmid, carrying numerous sets of genes involving in the biosynthesis of clavulanic acid. PMID- 27660793 TI - Draft Genome Sequence of Alternaria alternata Isolated from Onion Leaves in South Africa. AB - Alternaria alternata (Fr.) Keissler strain PPRI 21032 was isolated from onion leaves collected in Roodeplaat, Pretoria, South Africa. The whole genome of this strain was sequenced and produced a total of 33.12 Mb with a GC content of 50.9%. The whole genome comprises 11,701 predicted coding sequences. PMID- 27660794 TI - Draft Genome Sequence of a Diazotrophic, Plant Growth-Promoting Rhizobacterium of the Pseudomonas syringae Complex. AB - We report here the draft genome sequence of Pseudomonas syringae GR12-2, a nitrogen-fixing, plant growth-promoting bacterium, isolated from the rhizosphere of an Arctic grass. The 6.6-Mbp genome contains 5,676 protein-coding genes, including a nitrogen-fixation island similar to that in P. stutzeri. PMID- 27660795 TI - Whole-Genome Sequence of the Cheese Isolate Streptococcus macedonicus 679. AB - It is well recognized that Streptococcus macedonicus can populate artisanal fermented foods, especially those of dairy origin. However, the safety of S. macedonicus remains to be established. Here, we present the whole-genome sequence of strain 679, which was isolated from a French uncooked semihard cheese made with cow milk. PMID- 27660796 TI - Complete Genome Sequence of Plesiomonas shigelloides Type Strain NCTC10360. AB - Plesiomonas shigelloides is a Gram-negative rod within the Enterobacteriaceae family. It is a gastrointestinal pathogen of increasing notoriety, often associated with diarrheal disease. P. shigelloides is waterborne, and infection is often linked to the consumption of seafood. Here, we describe the first complete genome for P. shigelloides type strain NCTC10360. PMID- 27660797 TI - Complete Genome Sequence of the Intracellular Bacterial Symbiont TC1 in the Anaerobic Ciliate Trimyema compressum. AB - A free-living ciliate, Trimyema compressum, found in anoxic freshwater environments harbors methanogenic archaea and a bacterial symbiont named TC1 in its cytoplasm. Here, we report the complete genome sequence of the TC1 symbiont, consisting of a 1.59-Mb chromosome and a 35.8-kb plasmid, which was determined using the PacBio RSII sequencer. PMID- 27660798 TI - Effect of Calcium Phosphate-Hybridized Tendon Graft in Anatomic Single-Bundle ACL Reconstruction in Goats. AB - BACKGROUND: We previously developed a novel technique using an alternate soaking process that improves tendon-bone healing by hybridizing the tendon graft with calcium phosphate (CaP). However, the effects of the CaP-hybridized tendon graft on anatomic single-bundle anterior cruciate ligament (ACL) reconstruction remain unclear. PURPOSE: To determine the effects of CaP-hybridized tendon grafts compared with untreated tendon grafts 6 months after anatomic single-bundle ACL reconstruction using a goat model. STUDY DESIGN: Controlled laboratory study. METHODS: Animals were divided into a CaP group (n = 5 goats) and a control group (n = 5 goats), and we analyzed (1) knee kinematics and in situ forces under applied anterior tibial loads of 50 N and internal tibial torque of 2.0 N.m in the grafts at full extension and at 60 degrees and 90 degrees of knee flexion, (2) the mean percentage of bone tunnel enlargement using computed tomography (CT), and (3) the histology of the tendon-bone interface. RESULTS: The in situ forces under applied anterior tibial loads of 50 N at 60 degrees and 90 degrees of knee flexion in the CaP group were greater than those in the control group (P < .05). The red safranin-O-stained area, indicating glycosaminoglycans in the cartilage layers at the joint aperture sites of the anterior femoral and posterior tibial bone tunnel, was greater in the CaP group than that in the control group (P < .05). The lengths of the nonbonding gap area between the anterior femoral and posterior tibial bone tunnels in the control group were greater than those in the CaP group (P < .05). No significant difference could be detected in the mean percentage of bone tunnel enlargement between the 2 groups. CONCLUSION: The CaP-hybridized tendon graft enhanced tendon-bone healing at the joint aperture site in both anterior femoral and posterior tibial tunnels 6 months after anatomic single-bundle ACL reconstruction in goats. The in situ forces under applied anterior tibial loads at greater flexion angles in the CaP group increased compared with controls. CLINICAL RELEVANCE: Anatomic single bundle ACL reconstruction using CaP-hybridized tendon grafts may lead to better postoperative knee function. PMID- 27660799 TI - Comparisons of Patient Demographics in Prospective Sports, Shoulder, and National Database Initiatives. AB - BACKGROUND: There has been increased emphasis in orthopaedics on high-quality prospective research to provide evidence-based treatment guidelines, particularly in sports medicine/shoulder surgery. The external validity of these studies has not been established, and the generalizability of the results to clinical practice in the United States is unknown. HYPOTHESIS: Comparison of patient demographics in major prospective studies of arthroscopic sports and shoulder surgeries to patients undergoing the same procedures in the National Surgical Quality Improvement Program (NSQIP) database will show substantial differences to question the generalizability and external validity of those studies. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study utilized patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR), meniscectomy (MX), rotator cuff repair (RCR), and shoulder stabilization (SS) from the NSQIP database (2005-2013). Two prospective studies (either randomized controlled trials or, in 1 case, a major cohort study) were identified for each of the 4 procedures for comparison. Demographic variables available for comparison in both the identified prospective studies and the NSQIP included age, sex, and body mass index (BMI). RESULTS: From the NSQIP database, 5576 ACLR patients, 18,882 MX patients, 7282 RCR patients, and 993 SS patients were identified. The comparison clinical studies included cohort sizes as follows: ACLR, n = 121 and 2683; MX, n = 146 and 330; RCR, n = 90 and 103; SS, n = 88 and 196. Age differed significantly between the NSQIP and the patients in 6 of the 8 prospective clinical studies. Sex differed significantly between the NSQIP and the patients in 7 of the 8 prospective clinical studies. BMI differed significantly between the NSQIP and the patients of all 4 of the prospective clinical studies that reported this demographic variable. CONCLUSION: Significant differences exist for patient age, sex, and BMI between patients included in major sports medicine/shoulder prospective studies and corresponding patients undergoing the same procedures in a nationwide database of academic and community centers in the United States. Future work is needed to understand whether major prospective clinical studies-frequently performed in high-volume, specialized practices-are truly indicative of the types of patients treated and expected results in the general orthopaedic practice. This study additionally argues for the importance of initiating a national registry dedicated to patients undergoing orthopaedic procedures in the United States. PMID- 27660801 TI - High-contrast enzymatic immunohistochemistry of pigmented tissues. AB - Historically, standard enzyme immunohistochemistry has been accomplished with brown (DAB, diaminobenzidine) substrate. This can become problematic in pigmented tissues, such as the retina, where brown pigment of retinal pigmented epithelial (RPE) cells can be easily confounded with brown substrate. Although immunofluorescence detection methods can overcome this challenge, fluorescence may fade over a period of weeks, while enzyme substrates allow for more long lasting, archival results. In this report, we will describe a high-contrast enzyme immunohistochemistry method ideal for pigmented tissues that utilizes purple (VIP) substrate. We compared brown (DAB) and purple (VIP) substrates in enzyme immunohistochemistry experiments using human retina (paraffin sections) and monkey retinal pigmented epithelial cells (frozen sections), both containing brown pigmented cells. We compared substrates using several primary antibodies against markers that can be detected in the retina, including GFAP, VEGF, CD147 (EMMPRIN), RHO (rhodopsin) and PAX6. Methyl green was used as a counterstain for paraffin sections. A side-by-side comparison between DAB and VIP immunohistochemistry showed excellent contrast between pigmented cells and the purple VIP substrate in both human retinal tissue and monkey pigmented epithelial cells for all of the markers tested. This was a marked improvement over DAB staining in pigmented cells and tissues. For both paraffin sections and frozen sections of pigmented tissues, purple VIP substrate is an excellent alternative to brown DAB substrate and non-permanent immunofluorescence methods. PMID- 27660800 TI - Impact of Platelet-Rich Plasma on Arthroscopic Repair of Small- to Medium-Sized Rotator Cuff Tears: A Randomized Controlled Trial. AB - BACKGROUND: Increased interest in using platelet-rich plasma (PRP) as an augment to rotator cuff repair warrants further investigation, particularly in smaller rotator cuff tears. PURPOSE: To examine the effectiveness of PRP application in improving perioperative pain and function and promoting healing at 6 months after arthroscopic repair of small- or medium-sized rotator cuff tears. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This was a double blinded randomized controlled trial of patients undergoing arthroscopic repair of partial- or full-thickness rotator cuff tears of up to 3 cm who were observed for 6 months. Patients were randomized to either repair and PRP application (study group) or repair only (control group) groups. The patient-oriented outcome measures utilized were the visual analog scale (VAS), the Short Western Ontario Rotator Cuff Index (ShortWORC), the American Shoulder and Elbow Surgeons (ASES) form, and the Constant-Murley Score (CMS). Range of motion (ROM) and inflammatory and coagulation markers were measured before and after surgery. Magnetic resonance imaging was used at 6 months to assess retear and fatty infiltration rate. RESULTS: Eighty-two patients (41 males) with a mean age of 59 +/- 8 years were enrolled; 41 patients were included in each group. Both the PRP and control groups showed a significant improvement in their pain level based on the VAS within the first 30 days (P < .0001), with the PRP group reporting less pain than the control group (P = .012), which was clinically significantly different from days 8 through 11. The PRP group reported taking less painkillers (P = .026) than the control group within the first 30 days. All outcome measure scores and ROM improved significantly after surgery (P < .0001), with no between-group differences. No differences were observed between groups in inflammatory or coagulation marker test results (P > .05), retear (14% vs 18% full retear; P = .44), or fatty infiltration rate (P = .08). CONCLUSION: The PRP biological augmentation for repair of small- to medium-sized rotator cuff tears has a short term effect on perioperative pain without any significant impact on patient oriented outcome measures or structural integrity of the repair compared with control group. PMID- 27660802 TI - Errata: Quantum mechanism of light transmission by the intermediate filaments in some specialized optically transparent cells. AB - [This corrects the article DOI: 10.1117/1.NPh.4.1.011005.]. PMID- 27660803 TI - Automated and simultaneous fovea center localization and macula segmentation using the new dynamic identification and classification of edges model. AB - Detecting the position of retinal structures, including the fovea center and macula, in retinal images plays a key role in diagnosing eye diseases such as optic nerve hypoplasia, amblyopia, diabetic retinopathy, and macular edema. However, current detection methods are unreliable for infants or certain ethnic populations. Thus, a methodology is proposed here that may be useful for infants and across ethnicities that automatically localizes the fovea center and segments the macula on digital fundus images. First, dark structures and bright artifacts are removed from the input image using preprocessing operations, and the resulting image is transformed to polar space. Second, the fovea center is identified, and the macula region is segmented using the proposed dynamic identification and classification of edges (DICE) model. The performance of the method was evaluated using 1200 fundus images obtained from the relatively large, diverse, and publicly available Messidor database. In 96.1% of these 1200 cases, the distance between the fovea center identified manually by ophthalmologists and automatically using the proposed method remained within 0 to 8 pixels. The dice similarity index comparing the manually obtained results with those of the model for macula segmentation was 96.12% for these 1200 cases. Thus, the proposed method displayed a high degree of accuracy. The methodology using the DICE model is unique and advantageous over previously reported methods because it simultaneously determines the fovea center and segments the macula region without using any structural information, such as optic disc or blood vessel location, and it may prove useful for all populations, including infants. PMID- 27660804 TI - Automatic pericardium segmentation and quantification of epicardial fat from computed tomography angiography. AB - Recent findings indicate a strong correlation between the risk of future heart disease and the volume of adipose tissue inside of the pericardium. So far, large scale studies have been hindered by the fact that manual delineation of the pericardium is extremely time-consuming and that existing methods for automatic delineation lack accuracy. An efficient and fully automatic approach to pericardium segmentation and epicardial fat volume (EFV) estimation is presented, based on a variant of multi-atlas segmentation for spatial initialization and a random forest classifier for accurate pericardium detection. Experimental validation on a set of 30 manually delineated computer tomography angiography volumes shows a significant improvement on state-of-the-art in terms of EFV estimation [mean absolute EFV difference: 3.8 ml (4.7%), Pearson correlation: 0.99] with run times suitable for large-scale studies (52 s). Further, the results compare favorably with interobserver variability measured on 10 volumes. PMID- 27660805 TI - Automatic basal slice detection for cardiac analysis. AB - Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction of the left ventricle. Despite all the effort placed on automatic cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, suffers from high interobserver variability. As a result, an automatic algorithm for basal slice identification is required. Guidelines published in 2013 identify the basal slice based on the percentage of myocardium surrounding the blood cavity in the short-axis view. Existing methods, however, assume that the basal slice is the first short-axis view slice below the mitral valve and are consequently at times identifying the incorrect short-axis slice. Correct identification of the basal slice under the Society for Cardiovascular Magnetic Resonance guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that utilizes the two-chamber view to determine the basal slice while following the guidelines. To this end, an active shape model is trained to segment the two-chamber view and create temporal binary profiles from which the basal slice is identified. From the 51 tested cases, our method obtains 92% and 84% accurate basal slice detection for the end-systole and the end diastole, respectively. PMID- 27660806 TI - Robust x-ray image segmentation by spectral clustering and active shape model. AB - Extraction of bone contours from x-ray radiographs plays an important role in joint space width assessment, preoperative planning, and kinematics analysis. We present a robust segmentation method to accurately extract the distal femur and proximal tibia in knee radiographs of varying image quality. A spectral clustering method based on the eigensolution of an affinity matrix is utilized for x-ray image denoising. An active shape model-based segmentation method is employed for robust and accurate segmentation of the denoised x-ray images. The performance of the proposed method is evaluated with x-ray images from the public use dataset(s), the osteoarthritis initiative, achieving a root mean square error of [Formula: see text] for femur and [Formula: see text] for tibia. The results demonstrate that this method outperforms previous segmentation methods in capturing anatomical shape variations, accounting for image quality differences and guiding accurate segmentation. PMID- 27660807 TI - Impact of breast structure on lesion detection in breast tomosynthesis, a simulation study. AB - This study aims to characterize the effect of background tissue density and heterogeneity on the detection of irregular masses in breast tomosynthesis, while demonstrating the capability of the sophisticated tools that can be used in the design, implementation, and performance analysis of virtual clinical trials (VCTs). Twenty breast phantoms from the extended cardiac-torso (XCAT) family, generated based on dedicated breast computed tomography of human subjects, were used to extract a total of 2173 volumes of interest (VOIs) from simulated tomosynthesis images. Five different lesions, modeled after human subject tomosynthesis images, were embedded in the breasts and combined with the lesion absent condition yielded a total of [Formula: see text] VOIs. Effects of background tissue density and heterogeneity on the detection of the lesions were studied by implementing a composite hypothesis signal detection paradigm with location known exactly, lesion known exactly or statistically, and background known statistically. Using the area under the receiver operating characteristic curve, detection performance deteriorated as density was increased, yielding findings consistent with clinical studies. A human observer study was performed on a subset of the simulated tomosynthesis images, confirming the detection performance trends with respect to density and serving as a validation of the implemented detector. Performance of the implemented detector varied substantially across the 20 breasts. Furthermore, background tissue density and heterogeneity affected the log-likelihood ratio test statistic differently under lesion absent and lesion present conditions. Therefore, considering background tissue variability in tissue models can change the outcomes of a VCT and is hence of crucial importance. The XCAT breast phantoms have the potential to address this concern by offering realistic modeling of background tissue variability based on a wide range of human subjects, comprising various breast shapes, sizes, and densities. PMID- 27660808 TI - Tumor volume measurement error using computed tomography imaging in a phase II clinical trial in lung cancer. AB - To address the error introduced by computed tomography (CT) scanners when assessing volume and unidimensional measurement of solid tumors, we scanned a precision manufactured pocket phantom simultaneously with patients enrolled in a lung cancer clinical trial. Dedicated software quantified bias and random error in the [Formula: see text], and [Formula: see text] dimensions of a Teflon sphere and also quantified response evaluation criteria in solid tumors and volume measurements using both constant and adaptive thresholding. We found that underestimation bias was essentially the same for [Formula: see text], and [Formula: see text] dimensions using constant thresholding and had similar values for adaptive thresholding. The random error of these length measurements as measured by the standard deviation and coefficient of variation was 0.10 mm (0.65), 0.11 mm (0.71), and 0.59 mm (3.75) for constant thresholding and 0.08 mm (0.51), 0.09 mm (0.56), and 0.58 mm (3.68) for adaptive thresholding, respectively. For random error, however, [Formula: see text] lengths had at least a fivefold higher standard deviation and coefficient of variation than [Formula: see text] and [Formula: see text]. Observed [Formula: see text]-dimension error was especially high for some 8 and 16 slice CT models. Error in CT image formation, in particular, for models with low numbers of detector rows, may be large enough to be misinterpreted as representing either treatment response or disease progression. PMID- 27660809 TI - In memory of Helen Laburn and Claus Jessen. AB - It is with great sadness that we report the passing of our dear colleagues: Professor Helen Laburn and Professor Claus Jessen. We will always remember them. PMID- 27660810 TI - A Study to Determine the Incidence of Urinary Tract Infections in Infants and Children Ages 4 Months to 6 Years With Febrile Diarrhea. AB - OBJECTIVE: To determine the incidence of urinary tract infections (UTIs) in infants and children (4 months to 6 years of age) with febrile diarrhea, as outpatients. METHODS: This was a prospective institutional review board-approved study. patients (between 4 months and 6 years of age) were enrolled in the study who presented to the pediatric emergency room with a complaint of fever (rectal temperature 101 degrees F or more) and diarrhea (watery stools >3 in number). The patients were evaluated for state of hydration, and also urine samples were collected. For those children not toilet trained, urine specimens were collected by bladder catheterization, and for those children toilet trained, urine specimens were obtained by midstream collection method. The urine samples obtained were sent for analysis and culture. RESULTS: Eighty patients were enrolled in the study. The number of specimens obtained by clean catch midstream was 20, and by bladder catheterization was 60. None of the urine specimens obtained by both methods of collection grew any organism. There was no increased incidence of infections in male children whether circumcised (10/60) or uncircumcised (50/60). The mean temperature was 102.8 degrees F (range = 101 degrees F to 105 degrees F). STATISTICS: Using in silico online 2 * 2 chi(2) test by comparing both the positive and negative urine culture results, 2-tailed P value is <.0001. CONCLUSIONS: Our prospective randomized study concluded that there is no increased incidence of UTIs in infants and children (4 months to 6 years of age) with febrile diarrhea. PMID- 27660811 TI - In silico data analyses of recombinases GdDMC1A and GdDMC1B from Giardia duodenalis. AB - Giardia duodenalis is a worldwide protozoa known causing diarrhea in all vertebrates, humans among these. Homologous recombination is a mechanism that provides genomic stability. Two putative recombinases were identified in G. duodenalis genome: GdDMC1A and GdDMC1B. In this article, we describe the identification of conserved domains in GdDMC1A and GdDMC1B, such as: DNA binding domains (Helix-turn-helix motif, loops 1 and 2) and an ATPcap and Walker A and B motifs associated with ATP binding and hydrolysis, phylogenetic analyses among assemblages and three-dimensional structure modeling of these recombinases using bioinformatics tools. Also, experimental data is described about LD50 determination for ionizing radiation in trophozoites of G. duodenalis. Additionally, as recombinases, GdDMC1A and GdDMC1B were used to rescue a defective Saccharomyces cerevisiae Delta rad51 strain under genotoxic conditions and data is described. The data described here are related to the research article entitled "Characterization of recombinase DMC1B and its functional role as Rad51 in DNA damage repair in Giardia duodenalis trophozoites" (Torres-Huerta et al.,) [1]. PMID- 27660812 TI - Small punch tensile/fracture test data and 3D specimen surface data on Grade 91 ferritic/martensitic steel from cryogenic to room temperature. AB - Raw data from small punch tensile/fracture tests at two displacement rates in the temperature range from -196 degrees C to room temperature on Grade 91 ferritic/martensitic steel are presented. A number of specimens were analyzed after testing by means of X-ray computed tomography (CT). Based on the CT volume data detailed 3D surface maps of the specimens were established. All data are open access and available from Online Data Information Network (ODIN)https://odin.jrc.ec.europa.eu. The data presented in the current work has been analyzed in the research article "On the determination of the ductile to brittle transition temperature from small punch tests on Grade 91 ferritic martensitic steel" (M. Bruchhausen, S. Holmstrom, J.-M. Lapetite, S. Ripplinger, 2015) [1]. PMID- 27660813 TI - Data on the natural ventilation performance of windcatcher with anti-short circuit device (ASCD). AB - This article presents the datasets which were the results of the study explained in the research paper 'Anti-short-circuit device: a new solution for short circuiting in windcatcher and improvement of natural ventilation performance' (P. Nejat, J.K. Calautit, M.Z. Abd. Majid, B.R. Hughes, F. Jomehzadeh, 2016) [1] which introduces a new technique to reduce or prevent short-circuiting in a two sided windcatcher and also lowers the indoor CO2 concentration and improve the ventilation distribution. Here, we provide details of the numerical modeling set up and data collection method to facilitate reproducibility. The datasets includes indoor airflow, ventilation rates and CO2 concentration data at several points in the flow field. The CAD geometry of the windcatcher models are also included. PMID- 27660814 TI - Data on the transcriptional regulation of DNA damage induced apoptosis suppressor (DDIAS) by ERK5/MEF2B pathway in lung cancer cells. AB - The data included in this article are associated with the article entitled "DNA damage-induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes beta-catenin-mediated invasion" (J.Y. Im, S.H. Yoon, B.K. Kim, H.S. Ban, K.J. Won, K.S. Chung, K.E. Jung, M. Won) [1]. Quantitative RT-PCR data revealed that genetic or pharmacological inhibition of extracellular signal regulated kinase 5 (ERK5) suppresses DDIAS transcription in response to epidermal growth factor (EGF) in Hela cells. p300 did not interact with myocyte enhancer factor 2B (MEF2B), a downstream target of ERK5 and affect transcription of DDIAS. Moreover, DDIAS transcription is activated by ERK5/MEF2B signaling on EGF exposure in the non-small cell lung cancer cells (NSCLC) NCI-H1703 and NCI-H1299. DDIAS knockdown suppresses lung cancer cell invasion by decreasing beta-catenin protein level on EGF exposure. PMID- 27660815 TI - Vesical clear cell adenocarcinoma arising from endometriosis: A mullerian tumor, indistinguishable from ovarian clear cell adenocarcinoma. AB - Endometriosis is associated with increased rates of ovarian, particularly clear cell, adenocarcinomas. Malignant transformation of ovarian endometriosis is most common but rare cases have been reported in the bladder, abdominal wall, diaphragm, and rectum. We present the case of a 44-year-old female with vesical clear cell adenocarcinoma arising in a background of endometriosis in the absence of other pelvic endometriosis. The malignancy was diagnosed on transurethral resection of bladder tumor and managed with radical surgery. Histology and immunohistochemical findings were consistent mullerian origin and indistinguishable from similar tumors arising in the female genital tract. Extrapolating from the gynecologic literature, the recommendation was made for adjuvant chemotherapy. Further studies are needed to clarify the optimal treatment paradigm for ovarian and bladder clear cell adenocarcinomas. PMID- 27660817 TI - "Ich bin ein Reviewer" ("I am a Reviewer"). PMID- 27660816 TI - Isolation, Identification, and Antibiotic Susceptibility Testing of Salmonella from Slaughtered Bovines and Ovines in Addis Ababa Abattoir Enterprise, Ethiopia: A Cross-Sectional Study. AB - Salmonellae are ubiquitous, found in animals, humans, and the environment, a condition which facilitates transmission and cross contamination. Salmonella enterica serotypes exert huge health and economic impacts due to their virulence or carriage of antibiotic resistance traits. To address this significant issues with regard to public health, availability of adequate information on the prevalence and antibiotic resistance patterns of Salmonella, and establishment of adequate measures to control contamination and infection are needed. A cross sectional study was conducted to assess the level of Salmonella infection in slaughtered bovines and ovines at Addis Ababa abattoir. Samples were collected randomly and processed for identification and antimicrobial susceptibility testing of Salmonella spp. From 280 animals examined, 13 (4.64%) (8 bovines and 5 ovines) were positive, with most samples (12/13, 92%) comprising Salmonella Dublin. Very high level of resistance to some antibiotics used in human medicine was detected. Most isolates were susceptible to gentamycin and amikacin. Nine (69%) of all isolates were resistant to multiple antibiotics. Serotyping revealed 12 of 13 isolates to be of the Dublin serotype with 9,12:g,p:- antigenic formula. This study emphasizes the importance of improving the evisceration practice during slaughtering and restricting the use of antibiotics in farm animals. PMID- 27660818 TI - Electrochemically Modulated Nitric Oxide Release From Flexible Silicone Rubber Patch: Antimicrobial Activity For Potential Wound Healing Applications. AB - Herein, we report a novel design and the antimicrobial efficacy of a flexible nitric oxide (NO) releasing patch for potential wound healing applications. The compact sized polydimethylsiloxane (PDMS) planar patch generates NO via electrochemical reduction of nitrite ions mediated by a copper(II)-ligand catalyst using a portable power system and an internal gold coated stainless steel mesh working electrode. Patches are fabricated via soft lithography and 3-D printing. The devices can continuously release NO over 4 days and exhibit potent bactericidal effects on both Escherichia coli and Staphylococcus aureus. The device may provide an effective, safe, and less costly alternative for treating chronic wounds. PMID- 27660819 TI - Transport of Nitric Oxide (NO) in Various Biomedical grade Polyurethanes: Measurements and Modeling Impact on NO Release Properties of Medical Devices. AB - Nitric oxide (NO) releasing polymers are promising in improving the biocompatibility of medical devices. Polyurethanes are commonly used to prepare/fabricate many devices (e.g., catheters); however, the transport properties of NO within different polyurethanes are less studied, creating a gap in the rational design of new NO releasing devices involving polyurethane materials. Herein, we study the diffusion and partitioning of NO in different biomedical polyurethanes via the time-lag method. The diffusion of NO is positively correlated with the PDMS content within the polyurethanes, which can be rationalized by effective media theory considering various microphase morphologies. Using catheters as a model device, the effect of these transport properties on the NO release profiles and the distribution around an asymmetric dual lumen catheter are simulated using finite element analysis and validated experimentally. This method can be readily applied in studying other NO release medical devices with different configurations. PMID- 27660820 TI - Novel TK2 mutations as a cause of delayed muscle maturation in mtDNA depletion syndrome. AB - Recessive mutations in TK2 cause a severe mitochondrial DNA depletion syndrome (MDS),(1) characterized by severe myopathy from early infancy. Recent reports have suggested a wider clinical spectrum including encephalomyopathic form.(1,2) We report a patient with infantile-onset fatal encephalomyopathy presenting with extreme muscle fiber immaturity. PMID- 27660821 TI - Analysis of cystic fibrosis-associated P67L CFTR illustrates barriers to personalized therapeutics for orphan diseases. AB - Emerging knowledge indicates the difficulty in categorizing unusual cystic fibrosis (CF) mutations, with regard to both pathogenic mechanism and theratype. As case in point, we present data concerning P67L mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), a defect carried by a small number of individuals with CF and sometimes attributed to a channel conductance abnormality. Findings from our laboratory and others establish that P67L causes protein misfolding, disrupts maturation, confers gating defects, is thermally stable, and exhibits near normal conductance. These results provide one framework by which rare CF alleles such as P67L can be more comprehensively profiled vis-a vis molecular pathogenesis. We also demonstrate that emerging CF treatments - ivacaftor and lumacaftor - can mediate pronounced pharmacologic activation of P67L CFTR. Infrequent CF alleles are often improperly characterized, in part, due to the small numbers of patients involved. Moreover, access to new personalized treatments among patients with ultra-orphan genotypes has been limited by difficulty arranging phase III clinical trials, and off-label prescribing has been impaired by high drug cost and difficulty arranging third party reimbursement. Rare CFTR mutations such as P67L are emblematic of the challenges to "precision" medicine, including use of the best available mechanistic knowledge to treat patients with unusual forms of disease. PMID- 27660823 TI - Landmark-based Morphometric and Meristic Analysis of Serranidae. AB - The landmark-based morphometric and meristic analysis of the kelp grouper (Epinephelus bruneus), red spotted grouper (E. akaara) and seven-banded grouper (E. septemfasciatus) were performed to compare the differentiation of overall body shape and structure. The measurements of the morphometric dimensions were observed in 25 parts (truss dimension: 16 parts; head part dimension: 9 parts) of 38 morphometric dimensions and also meristic differences observed in 3 parts (dorsal fin, anal fin and caudal fin) of 6 meristic counts (P < 0.05). Observed morphometric characteristics primarily involved in truss and head part dimension, kelp grouper have larger values in caudal part of truss dimension, kelp grouper, red spotted grouper and seven-banded grouper have similar values in pectoral part of truss dimension, in addition to, results of head part dimension showed that red spotted grouper have smaller values in overall dimensions (P < 0.05). As meristic characteristics, kelp grouper have more number of anal fin rays than other fish, red spotted grouper have more number of dorsal soft rays than other fish, and seven spotted grouper have more number of anal soft rays, and caudal fin rays than other fish (P < 0.05). Photographed under the x-ray, kelp grouper have the most curved vertebral column and largest swim bladder than other fishes (P < 0.05). Our results of this study confirmed that 3 subfamily fishes adequately can distinguish with external body shape, and we hope that the results of our study could be used to identify in Serranidae family as taxonomical parameters. PMID- 27660824 TI - Early Osteological Development of Larvae and Juveniles in Red Spotted Grouper, Epinephelus akaara (Pisces: Serranidae). AB - We observed the osteological development of larval and juvenile red spotted grouper (Epinephelus akaara) in order to generate data for the assessment of skeletal deformities and to inform phylogenetic systematics research. Larvae and juveniles were obtained from a aquafarm in Muan-gun, Jeolla-namdo Province, Korea. The average water temperature at the time of breeding was 23.0 degrees C and average water salinity was 33.0 psu. Freshly hatched fish larvae had not undergone any ossification, but ossification of the parasphenoid bone, which forms the base of the cranium, occurred as the juveniles reached an average body length (BL) of 2.49 mm. At the same time, ossification of the preopercle and opercle occurred in the operculum, and ossification of the maxilla, which forms the upper jaw, and the dentary bones, which form the lower jaw, began. In addition, ossification of the vertebra occurred by formation of 7 vertebral centra and the neural spine in the abdominal vertebra. When the juveniles reached an average (BL) of 5.22 mm, ossification of the nasal, lateral ethmoid, and alisphenoid bones occurred in the cranium; ossification of the endopterygoid and metapterygoid bones began in the palatine region; and ossification of the hypohyal and interhyal bones occurred in the hyoid arch. At an average (BL) of 20.9 mm, ossification of the basisphenoid bone in the cranium and the suborbital bone in the orbital region occurred. Ossification of the vertebra then occurred by the formation of long pairs of ribs from the third to the ninth abdominal vertebrae, completing osteological development. PMID- 27660822 TI - Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma. AB - Infantile hemangioma (IH) is the most common vascular tumor of infancy, and it uniquely regresses in response to oral propranolol. MicroRNAs (miRNAs) have emerged as key regulators of vascular development and are dysregulated in many disease processes, but the role of miRNAs in IH growth has not been investigated. We report expression of C19MC, a primate-specific megacluster of miRNAs expressed in placenta with rare expression in postnatal tissues, in glucose transporter 1 expressing (GLUT-1-expressing) IH endothelial cells and in the plasma of children with IH. Tissue or circulating C19MC miRNAs were not detectable in patients having 9 other types of vascular anomalies or unaffected children, identifying C19MC miRNAs as the first circulating biomarkers of IH. Levels of circulating C19MC miRNAs correlated with IH tumor size and propranolol treatment response, and IH tissue from children treated with propranolol or from children with partially involuted tumors contained lower levels of C19MC miRNAs than untreated, proliferative tumors, implicating C19MC miRNAs as potential drivers of IH pathogenesis. Detection of C19MC miRNAs in the circulation of infants with IH may provide a specific and noninvasive means of IH diagnosis and identification of candidates for propranolol therapy as well as a means to monitor treatment response. PMID- 27660825 TI - Survival Rate and Hematological Responses with Temperature Changes of Red Spotted Grouper, Epinephelus akaara in South Korea. AB - The effect of sudden changes of water temperature (WT) on the survival rate and physiological responses of the red spotted grouper (Epinephelus akaara) were examined by manipulating WT control system for 9 days. Experimental condition was divided in two different regimes at low (from 10 degrees C to 4 degrees C, decreased 1C/d) and high (from 28 degrees C to 34 degrees C, increased 1 degrees C/d) WT. Survival rate of experimental fishes were observed, and determined the changes of hematological characteristics by analyzing plasma levels of cortisol, glucose, total protein, and electrolytes (Na(+), Cl-, K(+)). No mortality was observed until low WT 6 degrees C (144 h) and high WT 32 degrees C (96 h), and 100% mortality was observed at low WT 4 degrees C (216 h) and high WT 35 degrees C (171 h). Plasma levels of cortisol and glucose increased rapidly as decreasing WT, and the loss of swimming ability and respiration response was observed at low WT 7 degrees C and high WT 34 degrees C conditions. PMID- 27660826 TI - Effect of Lipopolysaccharide (LPS) Exposure on the Reproductive Organs of Immature Female Rats. AB - Lipopolysaccharide (LPS), an endotoxin, elicits strong immune responses in mammals. Several lines of evidence demonstrate that LPS challenge profoundly affects female reproductive function. For example, LPS exposure affects steroidogenesis and folliculogenesis, resulting in delayed puberty onset. The present study was conducted to clarify the mechanism underlying the adverse effect of LPS on the delayed puberty in female rats. LPS was daily injected for 5 days (50 MUg/kg, PND 25-29) to treated animals and the date at VO was evaluated through daily visual examination. At PND 39, animals were sacrificed, and the tissues were immediately removed and weighed. Among the reproductive organs, the weights of the ovaries and oviduct from LPS-treated animals were significantly lower than those of control animals. There were no changes in the weights of uterus and vagina between the LPS-treated and their control animals. Immunological challenge by LPS delayed VO. Multiple corpora lutea were found in the control ovaries, indicating ovulations were occurred. However, none of corpus luteum was present in the LPS-treated ovary. The transcription level of steroidogenic acute regulatory protein (StAR), CYP11A1, CYP17A1 and CYP19 were significantly increased by LPS treatment. On the other hand, the levels of 3beta- HSD, 17beta-HSD and LH receptor were not changed by LPS challenge. In conclusion, the present study demonstrated that the repeated LPS exposure during the prepubertal period could induce multiple alterations in the steroidogenic machinery in ovary, and in turn, delayed puberty onset. The prepubertal LPS challenge model used in our study is useful to understand the reciprocal regulation of immune (stress) - reproductive function in early life. PMID- 27660827 TI - Involvement of cAMP in the Human Serum-Induced Migration of Adipose-Derived Stem Cells. AB - Previously we observed that human adipose-derived stem cells (hADSCs) could form aggregation during culture in the presence of human serum (HS). In the present study, we have examined if the aggregation might result from the cell migration and analyzed the difference of cell adhesivity after culture in various conditions. When cells were cultured in fetal bovine serum (FBS) alone, there was no morphological change. Similarly, cells pretreated with FBS for 1 day or cultured in a mixture of FBS and HS showed little change. In contrast, cells cultured in HS alone exhibited formation of cell-free area (spacing) and/or cell aggregation. When cells cultured in FBS or pretreated with FBS were treated with 0.06% trypsin, almost cells remained attached to the dish surfaces. In contrast, when cells cultured in HS alone were examined, most cells detached from the dish by the same treatment. Treatment of cells with forskolin, isobutylmethyl xanthine (IBMX) or LY294002 inhibited the formation of spacing whereas H89 or Y27632 showed little effect. When these cells were treated with 0.06% trypsin after culture, most cells detached from the dishes as cells cultured in HS alone did. However, cells treated with IBMX exhibited weaker adhesivity than HS alone. Based on these observations, it is suggested that HS treatment might decrease the adhesivity and induce three-dimensional migration of hADSCs, in the latter of which cAMP signaling could be involved. PMID- 27660828 TI - Morphological Development of Embryo, Larvae and Juvenile in Yellowtail Kingfish, Seriola lalandi. AB - This study monitored the morphological development of embryo, larvae and juvenile yellowtail kingfish, Seriola lalandi, for their aquaculture. The fertilized eggs obtained by natural spawning were spherical shape and buoyant. Fertilized eggs were transparent and had one oil globule in the yolk, with an egg diameter of 1.35 +/- 0.04 mm and an oil globule diameter of 0.32 +/- 0.02 mm. The fertilized eggs hatched 67-75 h after fertilization in water at 20 +/- 0.5 degrees C. The total length (TL) of the hatched larvae was 3.62 +/- 0.16 mm. During hatching, the larvae, with their mouth and anus not yet opened. The yolk was completely absorbed 3 days after hatching (DAH), while the TL of post-larvae was 4.72 +/- 0.07 mm. At 40 DAH, the juveniles had grown to 30.44 +/- 4.07 mm in TL, body depth increased, the body color changed to a black, yellow, and light gray-blue color, and 3-4 vertical stripes appeared. At 45 DAH, the juveniles were 38.67 +/- 5.65 mm in TL and 10.10 +/- 0.94 mm in body depth. The fish were green with a light orange color, with 7 faint green-brown stripes on the sides of their body. At 87 DAH, the juveniles had grown to 236.11 mm in TL, 217.68 mm in fork length, and 136.5 g in weight. The fish resembled their adult form, with a light yellow green body color, loss of the pattern on the sides of their body, and a yellow coloration at the tip of the caudal fin. PMID- 27660829 TI - Management of Sexual Maturation and Natural Spawning of Captive- Reared Yellowtail Kingfish, Seriola lalandi, in an Indoor Rearing Tank. AB - This study describes results on sexual maturation and characteristics of natural spawned eggs to develop a method for the production of stable, healthy fertilized eggs from captive-reared yellowtail kingfish, Seriola lalandi. A total of 59 yellowtail kingfish were captured off the coast of Jeju Island, after which the broodstock was cultured in indoor culture tank (100 m(3)) until they were 6.1 14.9 kg in body weight. As part of the rearing management for induced sex maturation, the intensity of illumination was maintained at 130 lux. The photoperiod (light/dark; L/D) was set to a 12 L/12 D from October 2013 to January 2014, and 15 L/9 D from February 2014 to June 2014. Feeds comprised mainly EP (Extruded Pellets), with squid cuttlefish added for improvement of egg quality, and was given from April to June 2014. The first spawning of yellowtail kingfish occurred in May 3, 2014, at a water temperature of 17.0 degrees C. Spawning continued until June 12, 2014, with the water temperature set at 20.5 degrees C. Time of spawning was 26 times at this period. The total number of eggs that spawned during the spawning period was 4,449*10(3). The buoyant rate of spawning eggs and fertilization rate of buoyant eggs during the spawned period were 76.1% and 100%, respectively. The diameters of the egg and oil globule were 1.388 +/- 0.041 mm and 0.378 +/- 0.029 mm, respectively, which was higher in early eggs than in those from late during the spawned period. PMID- 27660830 TI - Adenosine Modulates the Oocyte Developmental Competence by Exposing Stages and Synthetic Blocking during In Vitro Maturation. AB - Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. By the inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage caused of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence.. PMID- 27660831 TI - Genetic Distances of Crucian Carp Populations analyzed by PCR Approach. AB - Genomic DNAs isolated from crucian carp of four rivers, belonging to the family Cyprinidae was amplified by seven oligonucleotides primers. In the present study, we employed hierarchical clustering method in order to reveal genetic distances and variations. Crucian carp was acquired from Hangang river (CAH), Geumgang river (CAG), Nakdonggang river (CAN) and Yeongsangang river (CAY). The primer BION-12 generated the most loci (a total of 50) with an average of 10 in the CAY population. The primer BION-10 generated the least loci (a total of 19), with an average of 3.8 in the CAG population, in comparison to the other primers used. Seven oligonucleotides primers made 16.7 average no. per primer of specific loci in the CAH population, 7.4 in the CAG population, 8.6 in the CAN population and 0.9 in the CAY population, respectively. The specific loci generated by oligonucleotides primers revealed inter-individual-specific characteristics, thus disclosing DNA polymorphisms. The dendrogram obtained by the seven oligonucleotides primers indicates four genetic clusters. The genetic distance that displayed significant molecular differences was between individuals no.06 and no.08 from the CAG population (genetic distance = 0.036), while the genetic distance among the five individuals that displayed significant molecular differences was between individuals no.08 and no.09 from the CAG population (genetic distance = 0.088). With regard to average bandsharing value (BS) results, individuals from CAY population (0.985+/-0.009) exhibited higher bandsharing values than did individuals from CAH population (0.779+/-0.049) (P<0.05). Relatively, individuals of CAY population were fairly closely related to that of CAN location (genetic distance between two populations<0.016). PMID- 27660832 TI - Rad51 Regulates Reprogramming Efficiency through DNA Repair Pathway. AB - Rad51 is a key component of homologous recombination (HR) to repair DNA double strand breaks and it forms Rad51 recombinase filaments of broken single-stranded DNA to promote HR. In addition to its role in DNA repair and cell cycle progression, Rad51 contributes to the reprogramming process during the generation of induced pluripotent stem cells. In light of this, we performed reprogramming experiments to examine the effect of co-expression of Rad51 and four reprogramming factors, Oct4, Sox2, Klf4, and c-Myc, on the reprogramming efficiency. Co-expression of Rad51 significantly increased the numbers of alkaline phosphatase-positive colonies and embryonic stem cell-like colonies during the process of reprogramming. Co-expression ofRad51 significantly increased the expression of epithelial markers at an early stage of reprogramming compared with control cells. Phosphorylated histone H2AX (gammaH2AX), which initiates the DNA double-strand break repair system, was highly accumulated in reprogramming intermediates upon co-expression of Rad51. This study identified a novel role of Rad51 in enhancing the reprogramming efficiency, possibly by facilitating mesenchymal-to-epithelial transition and by regulating a DNA damage repair pathway during the early phase of the reprogramming process. PMID- 27660833 TI - Novel Function of Sprouty4 as a Regulator of Stemness and Differentiation of Embryonic Stem Cells. AB - Sprouty (Spry) genes encode inhibitors of the receptor tyrosine kinase signaling cascade, which plays important roles in stem cells. However, the role of Spry4 in the stemness of embryonic stem cells has not been fully elucidated. Here, we used mouse embryonic stem cells (mESCs) as a model system to investigate the role of Spry4 in the stem cells. Suppression of Spry4 expression results in the decreases of cell proliferation, EB formation and stemness marker expression, suggesting that Spry4 activity is associated with stemness of mESCs. Teratoma assay showed that the cartilage maturation was facilitated in Spry4 knocked down mESCs. Our results suggest that Spry4 is an important regulator of the stemness and differentiation of mESCs. PMID- 27660834 TI - Practical "pearls" to help improve your care. AB - This month's review of the current uses of ultrasound in family medicine made me wonder whether ultrasound might become the stethoscope of the future. PMID- 27660835 TI - The benefits of doing ultrasound exams in your office. AB - Family medicine ultrasound is more accurate, more cost-effective, and less time consuming than you might imagine. Here's how it can improve your care. PMID- 27660836 TI - Shortness of breath: Looking beyond the usual suspects. AB - COPD and pneumonia come to mind when a patient is short of breath. But the signs and symptoms detailed here should lead you to suspect an uncommon cause. PMID- 27660837 TI - Sport-related concussion: How best to help young athletes. AB - Increased focus on sports concussion means you're likely to see greater numbers of children and adolescents with mild brain trauma. Here's what to keep in mind. PMID- 27660838 TI - Cervical cancer screening: How our approach may change. AB - Accumulating evidence has begun to alter priorities in testing modalities and in testing intervals, and further changes may be on the way. PMID- 27660839 TI - Swollen right hand and forearm . minor trauma to hand . previous diagnosis of cellulitis . Dx? AB - A 63-year-old woman with a history of hyperlipidemia presented to our hospital with a swollen right hand. The patient noted that she had closed her hand in a car door one week earlier, causing minor trauma to the right third metacarpophalangeal joint. Shortly after injuring her hand, she'd sought care at an outpatient facility, where she was given a diagnosis of cellulitis and a prescription for an oral antibiotic. The swelling, however, worsened, prompting her visit to our hospital. PMID- 27660840 TI - PURLs: On-demand pill protocol protects against HIV. AB - Finally, there's an effective prevention strategy--other than condoms--that can be used, as needed, by patients at high risk for HIV infection. PMID- 27660841 TI - Pruritic hyperpigmented patch on back. AB - The location of the pruritic area on this patient's back and the darkened patch that followed helped us to identify the cause of her chronic discomfort. PMID- 27660842 TI - Does oseltamivir shorten flu symptom duration? AB - Treatment of influenza virus infection with oral oseltamivir reduces time to alleviation of symptoms in adults and children by approximately one day compared with placebo. It reduces symptom duration even when initiated more than 2 days after symptom onset. PMID- 27660844 TI - Statins in Chronic Kidney Disease: When and When Not to Use Them. AB - This supplement reviews the evidence from clinical trials for the appropriate use of statins in patients with Chronic kidney disease (CKD). PMID- 27660843 TI - Severe pruritus . Crusted lesions affecting face, extremities, and trunk . Hepatitis C virus carrier . Dx? AB - The patient had visited various clinics for her complaints and was diagnosed as having contact dermatitis and senile pruritus. She was prescribed topical mometasone furoate and moisturizers. After 6 months of using this therapy, widespread grey-white plaques and minimal excoriation appeared on her face, scalp, and trunk. This was diagnosed as psoriasis, and the patient was prescribed topical corticosteroids, which she used for 9 months until she came to our clinic. PMID- 27660845 TI - Pulmonary Practice Pearls for Primary Care Physicians: Burden of COPD Exacerbations: Focus on Optimal Management and Prevention. AB - This supplement will address the prevalence, burden, and physical and psychological effects of chronic obstructive pulmonary disease (COPD) exacerbations, as well as management and prevention strategies. PMID- 27660846 TI - Editorial: Education for lifelong learning and referrals in practice. PMID- 27660847 TI - Gingival recession coverage: ?Do we still need autogenous grafts? AB - A variety of periodontal plastic surgical techniques have been proposed to obtain root coverage of gingival recession defects. All of the available root coverage procedures are able to provide significant root coverage for Miller Class I and II recession-type defects. However, only the subepithelial connective tissue graft in conjunction with a coronally advanced flap appears consistently effective across all clinical parameters, and is therefore currently considered the gold standard for gingival recession therapy. The major shortcomings of connective tissue graft procedures include patient morbidity associated with the second surgical site and limited availability of palatal donor tissue. More recently, 3D collagen matrices of human and porcine origin have been introduced as possible alternatives to autogenous connective tissue grafts in recession coverage procedures. This paper aims to give an overview on the possible use of collagen matrices as soft tissue substitutes and a possible alternative to connective tissue grafts in the surgical treatment of gingival recession defects. PMID- 27660848 TI - [Differences in morbidity of neobladder versus ileal conduit: a matched pair analysis on 134 patients]. AB - OBJECTIVE: The objective of this study is to evaluate whether performing an ileal conduit (IC) versus a neobladder(NB) during radical cystectomy (RC) can play a role on the morbidity of the surgical procedure. MATERIALS AND METHODS: At our institution since 2001, a database collecting the data of more than 450 patients who have undergone RC is perspectively maintained.The records of 246 patients submitted to RC and IC and 120 to RC and NB have been reviewed for the present study. By a binary logistic regression model, a propensity score was generated joining these factors: gender,age, smoking habit, Charlson' comorbidity score, platelet antiaggregants or oral anticoagulant therapy, ASA(American Society of Anesthesiologists) score, hydronephrosis, pathologic T stage, and lymphadenectomy. A group of patients submitted to IC and another to NB having the closer propensity score were created with a matching ratio of 1:1. The following features were compared between the two groups: operative time, blood loss,intraoperative complication rate, and postoperative complications rate (overall, clavien 1-2, clavien >=, related toRC, relate to urinary reconstruction).Results: One hundred thirty-four patients were selected, 67 submitted to NB, 67 to IC, well matched according to the desired features. No differences were noted for all the compared features.Conclusion: The morbidity of RC does not seem to be dependent on the choice to perform IC versus NB. PMID- 27660851 TI - Accumulation of Mg to Diffusive Gradients in Thin Films (DGT) Devices: Kinetic and Thermodynamic Effects of the Ionic Strength. AB - Availability of magnesium is a matter of concern due to its role in many environmental and biological processes. Diffusive Gradients in Thin Films (DGT) devices can measure Mg availability in situ. This work shows that Mg accumulation in water largely increases when ionic strength (I) decreases. This phenomenon can be explained from (i) the increase of both the association equilibrium (K) and rate (ka,R) constants for the reaction between Mg cations and resin sites, and (ii) the growing contribution of the partitioning of Mg cations at the resin-gel interface, as I decreases. Two theoretical models that take into account electrical interactions among Mg cations, background electrolyte, and resin sites can successfully be used to determine ka,R and K at each I. Both models yield similar ka,R values, which fulfill an expression for the kinetic salt effect. For freshwater (with a typical salinity of 10 mM and circumneutral pH), the binding of Mg is so fast and strong that the simplest perfect-sink DGT expression can be helpful to predict (overestimation lower than 5%) the accumulation in solutions with Mg concentrations up to 1 mM whenever the deployment time is below 9 h. Perfect sink conditions can still be applied for longer times, in systems with either a lower I or a lower Mg concentration. PMID- 27660852 TI - Quasiparticle Scattering in the Rashba Semiconductor BiTeBr: The Roles of Spin and Defect Lattice Site. AB - Observations of quasiparticle interference have been used in recent years to examine exotic carrier behavior at the surfaces of emergent materials, connecting carrier dispersion and scattering dynamics to real-space features with atomic resolution. We observe quasiparticle interference in the strongly Rashba split 2DEG-like surface band found at the tellurium termination of BiTeBr and examine two mechanisms governing quasiparticle scattering: We confirm the suppression of spin-flip scattering by comparing measured quasiparticle interference with a spin dependent elastic scattering model applied to the calculated spectral function. We also use atomically resolved STM maps to identify point defect lattice sites and spectro-microscopy imaging to discern their varying scattering strengths, which we understand in terms of the calculated orbital characteristics of the surface band. Defects on the Bi sublattice cause the strongest scattering of the predominantly Bi 6p derived surface band, with other defects causing nearly no scattering near the conduction band minimum. PMID- 27660850 TI - Stereoselective Degradation and Transformation Products of a Novel Chiral Insecticide, Paichongding, in Flooded Paddy Soil. AB - Paichongding is a chiral neonicotinoid insecticide currently marketed as racemate against sucking and biting insects. Under anaerobic condition, all paichongding stereoisomers underwent appreciable degradation in soil during 100 days of incubation, with estimated t1/2 values between 0.18 and 3.15 days. Diastereoselectivity in paichongding degradation was observed, with enantiomers (5S,7R)- and (5R,7S)-paichongding being more preferentially degraded in soils than enantiomers (5R,7R)- and (5S,7S)-paichongding. The half-lives of (5R,7R)- and (5S,7S)-paichongding were 3.05 and 3.15 days, respectively, as compared to 0.18 day for (5R,7S)- and (5S,7R)-paichongding. A total of nine intermediates were identified, of which depropylated paichongding was the predominant metabolite and appeared to be stable and recalcitrant to further degradation. Paichongding is degraded via denitration, depropylation, nitrosylation, demethylation, hydroxylation, and enol-keto tautomerism, producing chiral and biologically active products. These findings could have implications for environmental risk and food safety evaluations. PMID- 27660853 TI - Effect of Macrocycle Size on the Self-Assembly of Methylimidazolium Surfactant with Sulfonatocalix[n]arenes. AB - The effect of macrocycle size on the association of supramolecular amphiphiles composed of 4-sulfonatocalix[n]arene and 1-methyl-3-tetradecylimidazolium (C14mim+) was studied in aqueous solutions at pH 7. When the cavitand contained four sulfonatophenol units (SCX4), formation of spherical nanoparticles (NPs) was observed. By contrast, both supramolecular micelle (SM) and NP formation could be attained in the presence of NaCl when the larger, more flexible 4 sulfonatocalix[8]arene (SCX8) served as the host compound. The SCX8-promoted self assembly into the SM was enthalpically more favorable than the NP production, but the molar heat capacity changes in the two processes barely differed. An addition of 50 mM NaCl significantly increased the enthalpy of C14mim+-SCX8 NP formation, thereby making the self-organization into the SM more favorable. The transformation of SM into NP at high temperatures was due to the substantial entropic contribution to the driving force behind the NP formation. The critical micelle concentration (cmc) and the local polarity in the headgroup domain were considerably lower for the SM compared with those of the conventional C14mim+Br- micelle. PMID- 27660854 TI - Dynamic Melting Properties of Photoswitch-Modified DNA: Shearing versus Unzipping. AB - We use dynamic force spectroscopy to study the melting properties of azobenzene modified double-stranded DNA (azo-dsDNA) in both the shearing and unzipping geometries. By fitting the rupture force vs loading rate data with a Friddle-Noy De Yoreo model, we extract the location of the barrier (xt), the equilibrium force for the bond/transducer system (Feq), and the dissociation rate of dsDNA (koff0). We find that the koff0 of azo-dsDNA increases after UV illumination (365 nm) in both the shearing and unzipping geometries. Notably, we find that koff0 of azo-dsDNA in the unzipping geometry is 5-7 orders of magnitude larger than that in the shearing geometry, a result that helps explain the dependence of koff0 on the azobenzene photoswitch position during shearing experiments. We also extract the difference of free energy (DeltaGbu) between binding and unbinding states of azo-dsDNA with Feq and the system spring constant (kc). Our results provide important insights into the dynamic melting properties of azo-dsDNA and a new route for designing applications for reconfigurable sensors, stimulus-response materials, and nanoscale energy harvesting schemes based on photoswitch-modified biomolecules such as DNA. PMID- 27660855 TI - Discovery of Orally Efficacious Phosphoinositide 3-Kinase delta Inhibitors with Improved Metabolic Stability. AB - Aberrant signaling of phosphoinositide 3-kinase delta (PI3Kdelta) has been implicated in numerous pathologies including hematological malignancies and rheumatoid arthritis. Described in this manuscript are the discovery, optimization, and in vivo evaluation of a novel series of pyridine-containing PI3Kdelta inhibitors. This work led to the discovery of 35, a highly selective inhibitor of PI3Kdelta which displays an excellent pharmacokinetic profile and is efficacious in a rodent model of rheumatoid arthritis. PMID- 27660856 TI - Smoke-free policy in Poland on the example of the implementation into national law of the European Parliament and Council Directive 2014/40 /EU of 3 April 2014 on the approximation of laws, regulations and administrative provisions of the Member States concerning the production, presentation and sale of tobacco and related products, and repealing Directive 2001/37/WE. PMID- 27660857 TI - Practical measures of cognitive function and promotion of their performance in the context of research. AB - The aging of the population generates a number of very interesting research questions in the fields of medicine, psychology, sociology, demography, and many others. One of the issues subject to both intensive research by scientists and exploration by practitioners is associated with cognitive functions. The article presents current knowledge regarding practical actions in the field of promoting cognitive function using diagnostic programmes and training using modern technologies. An important aspect presented in this study is also related to the welfare of the maintenance or improvement of cognitive function. Information and communication technologies will contribute to the dissemination of computerized cognitive training, also personalized. PMID- 27660858 TI - Hypovitaminosis D and adipose tissue - cause and effect relationships in obesity. AB - In recent years, attention has been focused on pleiotropic directions of effects exerted by vitamin D. Epidemiological data indicate that deficiency of vitamin D in various population groups represents an increasingly widespread phenomenon, while a decreased serum concentration of calcitriol correlates with manifestation of civilization-linked diseases, including visceral obesity. This study aims at a review and synthesis of data linked to relationships between lowered vitamin D concentrations in blood and manifestation of obesity, and potential mechanisms which affect the concentration of the vitamin in conditions of an excessive accumulation of adipose tissue. Several variables are distinguished which can affect the status of vitamin D in obesity, but the key role in this respect is ascribed to the metabolic activity of visceral adipose tissue. Among others, the activity favours sequestration and modulation of calcitriol turnover. On the other hand, the effects of vitamin D on the process of adipogenesis and its involvement in remodelling of adipose tissue are pointed out. Also, several factors of an environmental nature (e.g. time of year/day, dietetic supply of vitamin D), genetic nature (e.g. genetic polymorphisms) and other conditioning (e.g. coexisting diseases, age, content of melanin in skin) cannot be bypassed as they may affect the concentration of vitamin D. Nevertheless, it still remains unresolved to what extent hypovitaminosis D represents the cause and to which it is the effect of obesity. PMID- 27660860 TI - Agriculture and snakebite in Bahia, Brazil - An ecological study. AB - This study investigated the correlation between the incidence of snakebite and indicators of agricultural development in municipal districts of the State of Bahia, Brazil. An ecological study was conducted with the 27,347 cases of snakebite poisoning reported to the Reportable Diseases National Information System in municipalities from the State of Bahia, Brazil, 2000-2009. The unit of analysis was each one of the 417 State municipalities, and the outcome variable was the average annual incidence of snakebite. Data were analyzed by multiple linear regression technique. The average annual incidence of snakebite ranged from zero to 221.96 per 100,000 inhabitants, according to the municipalities. The incidence of snakebite was positively and strongly associated with municipality characteristics: planted areas of cocoa and coffee, and the size of domestic bred chicken and bovine livestocks. It was concluded that several characteristics related to municipal agricultural profile were strongly associated with the incidence of snakebite. PMID- 27660859 TI - Molecular identification of Giardia duodenalis isolates from domestic dogs and cats in Wroclaw, Poland. AB - INTRODUCTION: Giardia duodenalis (G. intestinalis) is a common protozoan causing gastrointestinal disorders in many species of mammals. The genus of Giardia has high molecular diversity. Dogs and cats, in addition to their typical infection with assemblages C, D and F, may be a reservoir of zoonotic assemblages (A and B). OBJECTIVE: The aim of this study was a genetic characteristic of Giardia isolates of dogs and cats from the area of Wroclaw (Poland). MATERIALS AND METHOD: A total of 128 and 33 faecal samples from dogs and cats, respectively, were analyzed by routine coprological methods. The animals were diagnosed on the presence of G. duodenalis antigens in faeces soluble with the use of SNAP Giardia (IDEXX Laboratories) immunosorbent assay. 27 DNA isolates of Giardia were subjected to molecular identification (PCR-RFLP). RESULTS AND CONCLUSIONS: The prevalence of G. duodenalis was 21.1% (27/128) in dogs and 15.1% (5/33) in cats. In dogs, C assemblage was present in 18 (81%) positive stool samples, D assemblage in 2 (9%) samples, B assemblage present in one (4.5%), and mixed assemblages (C and D) occurred in one (4.5%) sample. F assemblage was found in 4 (80%) cats' positive stool samples and A assemblage occurred in one case (20%). Confirmation of the presence of A and B zoonotic assemblages suggests that infected pets can be a threat to human health. This study describes for the first time the presence of mixed infections within host-specific C and D assemblages in dogs in Poland. PMID- 27660861 TI - Seroepidemiological study of canine Leishmania infantum and Toxoplasma gondii infections in Shanghai, China, and analysis of risk factors. AB - The aim of this study was to determine the seroprevalence of Leishmania infantum and Toxoplasma gondii among household dogs in Shanghai (the most important industrial and commercial city in China), and to assess the possible risk factors associated with the infection. During 2014-2015, a total of 408 sera were collected from healthy household dogs and tested for L. infantum and T. gondii infection using commercial ELISA kits. The endemic characteristics according to gender, age group and breed were revealed by statistical descriptions and inference. The positive rates of L. infantum infection (24/408, 5.9%) were lower than those of T. gondii infection (37/408, 9.1%), and co-infection with both parasites was detected in seven dogs (7/408, 1.7%). Seropositivity for either parasite was more likely associated with age: the seroprevalence of T. gondii infection ranged from 1.3% (dogs<=1 year) - 18.7% (dogs>6 years), whereas that of L. infantum ranged from 1.3% (dogs<=1 year) - 9.9 % (dogs>6 years). Interestingly, the rates of exposure to both L. infantum and T. gondii were higher in males than in females. Relatively higher exposure rates for L. infantum and T. gondii were also observed in crossbred dogs compared with purebred dogs. However, neither gender nor breed is likely a determining factor for infection with these two parasites (P > 0.05). Identification of the risk factors that underlie these differences may help in the prevention of L. infantum and T. gondii infection in household dogs. To the best of our knowledge, this is the first report of L. infantum and T. gondii infection in household dogs in Shanghai, which shows that these two important parasites are still prevalent in this region. Therefore, it is necessary to take integrated strategies for prevention and control of infection in animals, which could help to reduce human infection in the region. PMID- 27660862 TI - Hepatitis C virus epidemiology and prevention in Polish and Swiss population - similar and contrasting experiences. AB - OBJECTIVE: The aim of the study was to review available data on HCV in Poland and Switzerland, in order to compare the two European countries with respect to epidemiological situation and efficiency of the response systems. MATERIALS AND METHOD: A search of registries, published and grey literature was performed to assemble data on prevalence, rate of detection of new cases, identified risk factors for transmission, mortality due to HCV, prevalence of HCC and the consequent liver transplantations, as well as data on treatment in Poland and Switzerland. RESULTS: Overall, the prevalence of anti-HCV antibodies was similar, not exceeding 1%. However, the major transmission routes of HCV infections were different: medical procedures in Poland and drug injections in Switzerland. By combining the available information it was also possible to demonstrate important differences in efficiency of the response systems. There was approximately 1 new diagnosis per 100 estimated undiagnosed cases in the population in Poland per year, compared to 6 in Switzerland, and the treatment rate per 100 estimated active infections was 2 and 4, respectively. CONCLUSIONS: Scaling up of the diagnosis and treatment is necessary in both countries; however, the means to achieve this might differ, taking into account the higher concentration of the infections in risk groups in Switzerland than in Poland. PMID- 27660864 TI - Students' attitudes to tick risks. AB - INTRODUCTION AND OBJECTIVES: The ever-increasing number of patients with tick borne diseases resulted in the presented study investigating the awareness, attitudes and knowledge among students about the threats arising from tick bites and preventive anti-tick practices. MATERIALS AND METHOD: Questionnaires concerning these issues were distributed amongst Czech and Polish university students of science. Responses were analyzed by nationality and by gender. RESULTS: Nearly all respondents were aware of the risks arising from ticks and could name at least one disease transmitted by ticks. The Czech students felt more threatened by tick-borne diseases, had more frequently suffered from Lyme borreliosis and were vaccinated against tick-borne encephalitis more often than the Polish students. A large number of the participants applied preventive measures against ticks in order to protect themselves. The Czech students believed in the effectiveness of repellents statistically more often than the Polish students, while effectiveness is the main criterion for selection of the right repellent in both groups. CONCLUSION: Differences in preferences between the two nations appeared in many areas, e.g. the Czechs felt more threatened by all kind of risks and suffered from Lyme disease more frequently. Gaps can still be found in both the knowledge and behaviour among the respondents. It can be expected that the general public knowledge of this issue is rather limited in comparison with the students participating in the study, who are systematically educated in the field. PMID- 27660863 TI - Agricultural injuries in Korea and errors in systems of safety. AB - INTRODUCTION: Agriculture is known to be a dangerous industry in Korea, as well as in other countries. According to earlier studies, the root cause of occupational injury can be identified with errors in the various systems of safety, and such identification is helpful for the prevention of occupational injury. OBJECTIVE: The aims of this study were to examine the root causes of cases of agricultural injury in Korea, based on insurance claims and identification of errors in systems of safety. MATERIALS AND METHOD: Using the Korean Mutual Aid Insurance's injury claim database, 277 injury cases were identified, of which 68 were contacted. Root causes were categorized, using the logic tree diagramming method and the systems of safety described in the literature. RESULTS: Seventy-five percent of all injuries were attributable to falls, strangulation, amputation and collision from flying and falling objects. 194 root causes were found for all injuries. The percentages of errors in all the systems of safety for each root cause were 24.7% - training/procedure, 20.3% - design, 11.9% - mitigation, 9.3% - human factor, 6.2% - maintenance/inspection, and 1.0% - warning/notification. The percentage of root causes which could not be categorized due to a shortage of information was 18.6%. CONCLUSIONS: It was found that most agricultural injuries were caused by a complex layer of root causes which were classified as errors in the systems of safety. This result indicates that not only training and personal protective equipment, but also regulation of safety design, mitigation devices, inspection/maintenance of workplaces, and other factors play an important role in preventing agricultural injuries. The identification of errors will help farmers to implement easily an effective prevention programme. PMID- 27660866 TI - Genotypic discrimination of Aspergillus fumigatus strain from related species within section fumigati. AB - INTRODUCTION AND OBJECTIVE: The aim was to make an exact diagnosis of 20 strains using molecular biological methods which were isolated from the atmosphere of the inpatient rooms in the Oncology and other departments of the Ege University Medical Faculty Hospital, and identified as Aspergillus fumigatus through phenotypic tests, and to determine their antibiotic susceptibility patterns. MATERIALS AND METHOD: It was confirmed that the 20 phenotypically-identified A. fumigatus strains belonged to the section Fumigati after they were tested by the ITS-PCR method. Their sequence analysis was performed and the results sent to the NCBI GenBank, and their accession numbers were obtained. For their exact diagnosis at the species level, the beta-tub (beta-tubulin) and rodA (RodletA) genes were examined with the multiplex PCR. Anti-fungal susceptibility of the 20 strains was determined according to the M38-A2 standards. RESULTS: As a result of ITS-PCR, it was confirmed that 19 of the 20 strains identified as A. fumigatus through the phenotypic methods belonged to the section Fumigati. However, after the detection of beta-tub and rodA genes, all 20 strains were identified as A. fumigatus. CONCLUSION: Although the results of the phenotypic and molecular biological tests applied to filamentous fungi do not often overlap, in this study, the results obtained from the molecular analysis confirmed the results of the phenotypic tests. However, 1 of the 20 strains phenotypically-identified as A. fumigatus was identified as Penicillium spp. as a result of ITS-PCR and sequence analysis. On the other hand, the profile obtained from beta-tub and rodA tests indicated that the strain was A. fumigatus. Based on these results, this strain is thought to belong to the Aspergilloides genus which has the features of both genera. PMID- 27660865 TI - First molecular evidence of [i]Borrelia burgdorferi[/i] sensu lato in goats, sheep, cattle and camels in Tunisia. AB - Borrelia burgdorferi sensu lato (s.l.) are tick-transmitted spirochaetes of veterinary and human importance. Molecular epidemiology data on ruminants are still lacking in most countries of the world. Therefore, the aim of this study was to estimate the rate of B. burgdorferi s.l. infection in ruminants from Tunisia. A total of 1,021 ruminants (303 goats, 260 sheep, 232 cattle and 226 camels) from different bioclimatic areas in Tunisia were investigated for the presence of B. burgdorferi s.l. DNA in blood by real time PCR. Prevalence rates were 30.4% (92/303) in goats, 6.2% (16/260) in sheep, 1.3% (3/232) in cattle, and 1.8% (4/226) in camels. Only tick species belonging to Rhipicephalus and Hyalomma genera were found on the investigated animals. In small ruminants, the prevalence of B. burgdorferi s.l. varied significantly according to localities and farms. Goats located in humid areas were statistically more infected than those located in sub-humid areas. Prevalence rates varied significantly according to age and breed in sheep, and age and tick infestation in goats. This study provides the first insight into the presence of B. burgdorferi s.l. DNA in ruminants in Tunisia, and demonstrates that host species such as goats and sheep may play an important role in natural Lyme disease cycles in this country. PMID- 27660867 TI - Environmental factors affecting the survival of soil dwelling Legionella longbeachae in water. AB - INTRODUCTION: Legionella longbeachae, a causative agent of Legionnaire's disease, has often been associated with potting soil and gardening, a feature quite distinct from other Legionella species. The precise transmission mechanism is still unknown, although due to the ecological coherence of the soil and water there is a potential risk of infection by contaminated stagnant water in the garden. OBJECTIVE: The aim of the study was to explore the ability of L. longbeachae to survive in stagnant tap water usually used for watering in gardens. The influence of different factors (temperature, pH and NaCl concentration) on L. longbeachae survival in stagnant tap water was also tested. RESULTS: The result showed that L. longbeachae is viable in stagnant tap water over 100 days at 4 degrees C and 25 degrees C. The survival of L. longbeachae exposed to different pH and NaCl concentration suggests resistance to low pH values (pH2 and pH5) and all tested NaCl concentrations at temperatures lower than 25 degrees C. The ability of L. longbeachae to persist in stagnant tap water should be taken seriously in the risk assessments as a possible hidden reservoir of infection. PMID- 27660868 TI - Acrylamide content in cigarette mainstream smoke and estimation of exposure to acrylamide from tobacco smoke in Poland. AB - INTRODUCTION AND OBJECTIVE: Acrylamide is a "probably human carcinogen" monomer that can form in heated starchy food as a result of a reaction between asparagine and reducing sugars via Maillard reaction. The main source of acrylamide in human diet are potato products, cereal products and coffee. Tobacco smoke may be another significant source of exposure to acrylamide. The aim of our study was to determine acrylamide content in cigarettes available on the Polish market and to estimate the exposure to acrylamide originating from tobacco smoke in smokers in Poland. MATERIALS AND METHODS: The material was cigarettes of the top five brands bought in Poland and tobacco from non-smoked cigarettes. Acrylamide content in cigarettes mainstream smoke was determined by LC-MS/MS. Exposure assessment was carried out using analytical data of acrylamide content in cigarettes and the mean quantity of cigarettes smoked daily by smokers in Poland, assuming body weight at 70 kg. RESULTS: The mean content of acrylamide was 679.3 ng/cigarette (range: 455.0 - 822.5 ng/cigarette). The content of acrylamide was evidenced to correlate positively with total particulate matter (TPM) content in cigarettes. The estimated average exposure to acrylamide from tobacco smoke in adult smokers in Poland is 0.17 MUg/kg b.w./day. CONCLUSIONS: Our results demonstrate that tobacco smoke is a significant source of acrylamide and total exposure to acrylamide in the population of smokers, on average, is higher by more than 50% in comparison with non-smokers. Our estimation of exposure to acrylamide from tobacco smoke is the first estimation taking into account the actual determined acrylamide content in the cigarettes available on the market. PMID- 27660869 TI - Healthcare model with use of information and communication technology for patients with chronic disease. AB - INTRODUCTION AND OBJECTIVE: The healthcare system is positioned in the patient's environment and works with other determinants of the treatment. Patient care requires a whole system compatible to the needs of organizational and technical solutions. The purpose of this study is to present a new model of patient oriented care, in which the use of information and communication technology (ICT) can improve the effectiveness of healthcare for patients with chronic diseases. MATERIAL AND METHODS: The study material is the process of healthcare for chronically ill patients. Knowledge of the circumstances surrounding ecosystem and of the patients' needs, taking into account the fundamental healthcare goals allows us to build a new models of care, starting with the economic assumptions. The method used is modeling the construction of efficient healthcare system with the patient-centered model using ICT tools. RESULTS: We present a new systemic concept of building patient's environment in which he is the central figure of the healthcare organization - so called patient centered system. The use of ICT in the model of chronic patient's healthcare can improve the effectiveness of this kind of care. The concept is a vision to making wide platform of information management in chronic disease in a real environment ecosystem of patient using ICT tools. CONCLUSIONS: On the basis of a systematic approach to the model of chronic disease, and the knowledge of the patient itself, a model of the ecosystem impacts and interactions through information feedback and the provision of services can be constructed. ICT assisted techniques will increase the effectiveness of patient care, in which nowadays information exchange plays a key role. PMID- 27660870 TI - Hospitalization of injured immigrants in Poland - Demographic profile and diagnosis. AB - INTRODUCTION AND OBJECTIVE: More and more immigrants gradually come to Poland. Little is known, however, about their health situation or their injuries. The objective of this study was to analyse the cases of hospitalization of immigrants due to injuries in 2008-2010, including the number and demographic characteristics of the patients, as well as the nature of injury according to ICD 10 (S00-T98). MATERIAL AND METHODS: The analysis was conducted on the basis of data from the General Hospital Morbidity Study. All the cases of hospitalization due to injuries were covered by the analysis, and a group of foreigners was compared to the general population. RESULTS: The number of foreigners hospitalized due to injuries ranged from 4.6-21.2 thousand in the subsequent years. The share of hospitalization due to injuries equalled 8.2-11.9% of all foreigners' hospital stay. The majority were males, but the proportion of females gradually increased up to 36.7% in 2010. The average age of the hospitalized gradually decreased to the age of 35.2 in 2010. The structure of the nature of injury was different from that of the general population. Prevailing types of injuries were minor injuries of wrist, hand, ankle and foot. Open wounds of the head were also common. CONCLUSIONS: Results of the analysis indicate the most important tendencies related to immigrants' injuries. Further research, as well as monitoring the foreigners' health status is necessary. Taking preventive measures is essential among the most vulnerable group - male immigrants aged 15 19. PMID- 27660871 TI - Hospitalization of injured immigrants in Poland - Utilization of in-patient services. AB - INTRODUCTION AND OBJECTIVE: In 2008-2010, the number of foreigners hospitalized due to injuries in Poland ranged from approximately 5-21 thousand. The aim of this study was to analyse the utilization of in-patient services by injured immigrants in 2008-2010, including mode of admission (i.e. referral), mode of discharge, average length of patient stay, seasonality and spatial distribution of hospital admissions. MATERIAL AND METHODS: Analysis was conducted on the basis of data from the General Hospital Morbidity Study. All cases of hospitalization due to injuries were covered by the analysis, and a group of foreigners was compared to the general population. RESULTS: The percentage of immigrants admitted by acute admission through self-referral increased to 80.9% in 2010. The great majority (79.4%) were discharged to in-patient care. The immigrants' stay in the hospital was approximately twice as short than that of an average patient with injury. Immigrants and the rest of the patients were admitted to hospitals in different seasonal rhythm. The great majority of foreigners were treated in hospitals located in two (out of 16) provinces. CONCLUSIONS: This study supports the need for understanding the immigrant experience when accessing health care, as well as the need for further research and contribution of public health. PMID- 27660872 TI - Prevalence of hypertension and major cardiovascular risk factors in healthy residents of a rural region in south-eastern Poland - 1997-2008/9. AB - INTRODUCTION AND OBJECTIVE: The aim of this study was to show the prevalence of hypertension and major risk factors of cardiovascular disease among healthy adults in an agricultural region of south-eastern Poland, and the changes which have occurred in this area during the 12-year follow-up. MATERIALS AND METHOD: 1,233, mostly rural inhabitants of Zamosc County without previous history of diabetes and CVD were subjected to analysis. Prevalence of hypertension and major cardiovascular risk factors were evaluated. Changes in the prevalence of risk factors between 1997 - 2008 were analyzed. RESULTS: 33.0% of the examined population are active smokers, and there was a 1.8-fold increase (p = 0.0009). The percentage of people with hypercholesterolemia between 1997 - 2008/9 increased almost 2-fold (p<0.0001) and now it is 62.3%. The number of people with high blood pressure decreased nearly by a half (46%, p <0001) and it is currently 25.8%. Improper waist circumference was observed in 32.8% of the population (33.1% women, 26.5% men). Abdominal obesity decreased among men (48%; p=0.0008) and rural residents (29%, p=0.01). In comparison with 1997, in 2008-2009, the cardiovascular risk assessed using SCORE tables increased. The percentage of people with high-risk (>=5%) almost tripled in the general population (p=0.0183) and increased 4-fold in men (p=0.0145). CONCLUSIONS: Detection of hypertension in the rural region in which the survey was carried out is still too low. Actions against tobacco addiction should be a major component of health-education programmes for the rural areas of south-eastern Poland. PMID- 27660873 TI - Intentional poisonings in urban and rural children - a 6-year retrospective single centre study. AB - INTRODUCTION: Intentional poisonings among children and adolescents are a problem not only for paediatricians, but also constitute a big issue for public health. In many countries worldwide, including Poland, an increase has been observed in suicidal behaviours at developmental age. OBJECTIVE: The aim of the study was a retrospective evaluation of patients hospitalized due to intentional poisoning in the Department of Paediatrics, Children's University Hospital in Lublin, Poland, in 2007-2012. MATERIALS AND METHODS: In the study period, 149 patients were hospitalized in the Paediatric Department of the Children's University Hospital in Lublin, due to intentional poisoning with medicines or other chemical substances. The study group comprised 135 girls and 14 boys; The majority of patients (n=105) were urban inhabitants, and only 44 lived in the rural areas. Medical records were analyzed, with consideration of medical, psychological and psychiatric examinations. RESULTS: Girls constituted as much as 90.6% of the study group. The majority of patients lived in urban areas - 70.46%. A total of 16.77 % of patients came from incomplete families. Alcohol problem occurred in 19 families. The most frequent cause of a suicide attempt was conflict in the family, followed by school problems. During the 6-year-study period, an upward tendency in the incidence of intentional poisoning was observed, particularly in the first 4 years. DISCUSSION AND CONCLUSION: Suicide attempts in adolescents were mostly undertaken by girls from the urban environment. The majority of those attempts were caused by family problems, including alcoholism. PMID- 27660874 TI - Nasal patency in Poles in the light of research as part of the project on Epidemiology of Allergic Diseases in Poland. AB - OBJECTIVE: The aim of this study was to estimate the reference values for nasal inspiratory flow in the study population in Poland as part of the project on Epidemiology of Allergic Diseases in Poland (ECAP). MATERIALS AND METHOD: The study subjects were a group of 4,137 people: 1,136 children aged 6-7 years (561 girls and 575 boys), 1,123 adolescents aged 13-14 years (546 girls, 577 boys) and 1,878 adults (1,145 women, 733 men), residing in seven large Polish cities. The method used in the study was the measurement of the peak nasal inspiratory flow (PNIF) using a special mask for rhinomanometry tests, with a measurement scale of 20-350 L/min. Measurements were conducted twice: once before and once after nasal mucosa vasoconstriction with a 0.1% xylometazoline (Xylometazolinum) solution. RESULTS: Nasal patency rates increased with age in healthy subjects (children aged 6-7 years: 75.95 L/min; teenagers aged 13-14 years: 91.44 L/min and adults: 97.13 L/min (P<0.05). Similarly significant correlations were observed in the study group based on the region of residence (P<0.05). A moderate correlation was observed between PNIF and height as well as weight (with correlation coefficients r=0.51, P<0.05; and r=0.49, P<0.05, respectively). Interestingly, the observed difference in nasal vasoconstriction varied considerably between study subgroups with respect to the pre-determined criteria of age, gender, place of residence, and clinical diagnosis (allergic rhinitis vs. healthy controls), with the mean rates of 25-28%. CONCLUSIONS: Any attempt to determine reference values for a given study population should include a number of variables, such as age, height, body weight, which can noticeably affect study results. PMID- 27660875 TI - Condition of informal caregivers in long-term care of people with dementi. AB - INTRODUCTION: Caregivers of demented relatives devote their time and attention in order to help the beloved members of the family. Those who are informal caregivers require support in order to avoid being overburdened. Many such caregivers may suffer from chronic health problems, for instance, depression. OBJECTIVE: The aim was to assess the factors of depression in caregivers, and to discover the determinants of depression among informal family caregivers of demented individuals. MATERIALS AND METHOD: Forty-one caregivers in the research group were administered a questionnaire which included the caregivers' demographics. Caregiver's level of depression was measured by the scale of the Centre for Epidemiology Scale for Depression. The relationship between depression and demographic features was analyzed. Data were analyzed using STATISTICA 8.1 (StatSoft). Analysis of the results was performed using the Kolmogorov-Smirnov test of normality. Pearson correlation coefficient was also used. RESULTS: Referring to The Centre for Epidemiology Scale for Depression, the average score in the study group was 18 +/- 7.49. There was no statistically significant relationship between the level of depression and such factors as caregiver's age, time of care of demented relative, and type of kinship and pain. CONCLUSIONS: Although there was no relationship between the level of depression and demographic features, the problem with quality of life, worries and grief which may appear, seemed to be sufficient reason for organizing the prevention of depression for all informal caregivers of persons with dementia. PMID- 27660876 TI - Influence of dietary calcium intake on quantitative and qualitative parameters of bone tissue in Polish adults. AB - INTRODUCTION: The objective of the study was to assess dietary calcium intake in the Polish population and its influence on selected parameters of bone tissue. MATERIALS AND METHOD: 1,129 osteoporosis treatment-naive subjects, aged 20-80 years, randomly selected, were involved in the study. Bone status was established using densitometry of spine and hip and quantitative ultrasound of the calcaneus. Dietary calcium intake was calculated according to data gathered in a questionnaire. RESULTS: Median calcium intake was 746 mg; 72% of subjects had calcium intake below the recommended dose. Calcium intake correlated negatively with age (r = -0.15; p<0.001) and positively with BMD in the spine (r = 0.06; p<0.05) and in the femoral neck (r = 0.07; p < 0.05). In subjects with the lowest calcium intake, a significantly lower femoral neck BMD and heel stiffness was noticed than in subjects with the highest calcium intake. However, multiple regression analysis showed that dietary calcium was not a predictor of low BMD, both in the hip and spine, as well as of bone stiffness in contrast to age, low BMI and female gender (p<0.0001). In all factors regression analysis, a weak influence of calcium intake on BMD was shown only in the subgroup of premenopausal women (beta = 0.1; p<0.05). CONCLUSIONS: In most subjects, dietary calcium intake was below the recommended dose; however, its influence on bone seems to be weak, except for persons with the greatest deficiency of dietary calcium and the subgroup of premenopausal women. PMID- 27660877 TI - Physical activity patterns, depressive symptoms and awareness of cardiovascular risk factors in postpartum women. AB - INTRODUCTION AND OBJECTIVES: Although physical activity has been found to reduce the risk of cardiovascular diseases and depression in the general population, little is known about physical patterns and the link with postnatal depressive symptoms and awareness of cardiovascular risk factors in postpartum women. The aim of this study was to examine physical activity patterns and their link to depressive symptoms in postpartum women. The secondary endpoint was the assessment of health awareness in women six months after delivery. MATERIAL AND METHODS: Eighty postpartum women with a mean age of 27+/-4 years (group A - 40 physically active women, group B - 40 women leading a sedentary lifestyle) completed a self-report questionnaire and The Edinburgh Postnatal Depression Scale (EPDS) questionnaire. RESULTS: In group A, the types of physical activity undertaken in the six-month period after delivery were as follows: 20 women - housework (180 min/session), 18 women - gentle walks (180 min/session), 16 women group fitness classes (60 min/session), 6 - rapid walking (40 min/session), 3 women - swimming (60 min/session), 2 women - jogging (45 min/session), 1 woman - squash, (45 min/session) 1 - dancing (90 min/session), 1 - tennis (60min/session). Group B declared a sedentary lifestyle and physical activity of less than 30 min a day. The level of health awareness was statistically better in women who were physically active six months after delivery than in women who led a sedentary lifestyle. On a scale with a maximum 55 points, the mean scores were 47.4 in group A and 31.2 in group B (p=0.001). Depressive symptoms were more pronounced in group B. Twenty seven women from group A and three women from group B returned to their pre-pregnancy weight (p=0.04). CONCLUSIONS: Women who were physically active after delivery were characterized by higher health awareness and more frequent return to pre-pregnancy weight. Physical activity may be important for reducing the risk of postnatal depression. PMID- 27660878 TI - The role of serological testing for Chlamydia trachomatis in differential diagnosis of pelvic pain. AB - INTRODUCTION: Pelvic pain is typically associated with pelvic inflammatory disease (PID). The most common cause of PID is Chlamydia trachomatis. The aim of this study was to verify the role of serological testing for Chlamydia trachomatis in patients with suspected PID. MATERIALS AND METHOD: The retrospective study included 185 patients with pelvic pain hospitalized at the Department of Obstetrics and Gynecology in 2003 and 2004. Titers of anti Chlamydia trachomatisIgG and IgA were measured by means ELISA immunoassays. Erythrocyte sedimentation rate (ESR), serum concentration of C-reactive protein (CRP) and leukocyte count (WBC) were also determined. Final diagnosis was established on the basis of laparoscopic examination. RESULTS: The presence of anti-Chlamydia trachomatis antibodies correlated significantly with abnormal values of ESR, WBC and CRP. The most common laparoscopic pathology were pelvic adhesions, typically found in women with elevated titers of anti-Chlamydia trachomatis IgG. Cconclusion. Serological examination for Chlamydia trachomatis is helpful in evaluation of patients with suspected PID. Elevated titers of anti Chlamydia trachomatis antibodies are frequently associated with laparoscopic evidence of pelvic adhesions and inflammation. PMID- 27660879 TI - Evaluation of the hospital environment for women with endometrial cancer. AB - INTRODUCTION AND OBJECTIVES: The aim of the study was describe the factors determining the evaluation of the hospital environment, especially satisfaction with care and individual needs of cancer patients. MATERIAL AND METHODS: The study comprised 80 women with endometrial cancer diagnosed and treated surgery in the Clinic of Gynaecology and Obstetrics in Rzeszow, Poland, between 2011-2012. The study used 3 questionnaires: the Goals Attainment Scaling (GAS) questionnaires, and questionnaires developed by the EORTC Quality of Life group, i.e. the QLQ C-30 (general module) and the In- PATSAT-32. RESULTS: Respondents indicated 36 goals/expectations and the most common (over 50%) concerned the normal course of the post-operative period. The overall index of all goals which were met was 7.0 points. General quality of life reported by respondents before surgery was at a medium level (52.3+16.8%). Emotional functioning received the lowest scores (61.0+18.8%). Most respondents assessed manual skills of hospital doctors and nurses as the best in the In-PATSAT 32 scale i.e. 69.9+/-14.7% and 67.3+/-16.1%, respectively. The worst ratings concerned access to hospital from the outside (50.8+/-16.9%) and easy orientation inside the buildings (55.9+/ 16.0%). CONCLUSIONS: Analysis of correlations between GAS and the In-PATSAT32 scales proved that they cannot be used interchangeably since they measure different aspects of a patient's satisfaction with hospital care. For this reason, the application of idiographic and nomothetic tests among cancer patients is helpful for evaluation of the hospital environment. PMID- 27660880 TI - Intensification of menopausal symptoms among female inhabitants of East European countries. AB - The objective of the study was analysis of the occurrence and intensity of menopausal symptoms in postmenopausal women from Poland, Belarus, Ukraine, Czech Republic, Slovakia and Poland. The study was conducted during the period 2014 2015 among postmenopausal women living in the areas of Poland, Belarus, Ukraine, Czech Republic and Slovakia. The degree of menopausal complaints was assessed using the Kupperman Menopausal Index and Greene Climacteric Scale. The respondents were additionally asked about age, educational level, place of residence, marital status and age at last menstrual period. Into the study were enrolled women aged 50-65, minimum 2 years after the last menstrual period, who had a generally good state of health and did not use hormone replacement therapy. The results were subjected to statistical analysis. The intensity of all menopausal symptoms measured by the Kupperman Menopausal Index and Greene Climacteric Scale was similar in Poland, Czech Republic and Slovakia. In these countries, severe, moderate and mild menopausal symptoms measured by Kupperman Menopausal Index occurred with a similar frequency. Similar results were also obtained in the subscales of psychological, somatic and vasomotor symptoms according to the Greene Climacteric Scale. Nearly a half of the women from Belarus did not report symptoms measured by Kupperman Menopausal Index. They obtained significantly lower menopausal complaints in the subscales of psychological and somatic symptoms according to the Greene Climacteric Scale, compared to the inhabitants of the remaining countries. The majority of women from the Ukraine had mild menopausal symptoms as measured by the Kupperman Menopausal Index. They had significantly more severe complaints in the subscales of psychological, somatic and vasomotor symptoms according to the Greene Climacteric Scale, compared to the inhabitants of the remaining countries in the study. The intensity of menopausal symptoms in women from Ukraine and Belarus was related with educational level, place of residence, and marital status, whereas in women from Poland, Czech Republic and Slovakia, only with marital status. PMID- 27660881 TI - Use of marijuana for medical purposes. AB - Cannabis is the most popular illicit drug on the European market. Over 16 million young Europeans have used it at least once in the last few years. The recent trends in the consumption of marihuana differ between countries. Some countries face an increase in the prevalence of cannabis use, including Poland, where the level cannabis use has been systematically increasing since the 1990's. According to a recent ESPAD study, 19% of Polish adolescents aged 15-16 have used cannabis in the last year. Marihuana is also a leading substance when analyzing the data of seizures and crimes. The recent EMCDDA Annual report on the drug situation in Europe notes the increasing potency in cannabis available on the market. Some countries face an increasing number of emergencies caused by marihuana, which was unlikely to have happened previously. In almost all European countries there is an ongoing discussion about loosening marijuana laws or its complete legalization. There is also ongoing discussion on the use of marihuana in therapy as a medicine. Many scientific studies are being conducted in this field. Some of the results are promising; however, there is no well-designed human trial which would unequivocally confirm that medical cannabis is effective as a medicine, or more effective than other medicines on the market. The problem is that the debate on the medical use of marihuana becomes more ideological and less professional. The medical use of marihuana is strongly supported by organizations lobbying for the legalization of cannabis use. Research on the medical use of cannabis should be continued, as there are some promising results supporting therapy in different medical conditions. However, the use of cannabis as a medicine should be discussed only among professionals. If marihuana is to be used for medical purposes, the fact that it is the most popular illicit drug in Europe is irrelevant. PMID- 27660882 TI - Anomalous Dynamics of Water Confined in Protein-Protein and Protein-DNA Interfaces. AB - Confined water often exhibits anomalous properties not observable in the bulk phase. Although water in hydrophobic confinement has been the focus of intense investigation, the behavior of water confined between hydrophilic surfaces, which are more frequently found in biological systems, has not been fully explored. Here, we investigate using molecular dynamics simulations dynamical properties of the water confined in hydrophilic protein-protein and protein-DNA interfaces. We find that the interfacial water exhibits glassy slow relaxations even at 300 K. In particular, the rotational dynamics show a logarithmic decay that was observed in glass-forming liquids at deeply supercooled states. We argue that such slow water dynamics are indeed induced by the hydrophilic binding surfaces, which is in opposition to the picture that the hydration water slaves protein motions. Our results will significantly impact the view on the role of water in biomolecular interactions. PMID- 27660883 TI - Correction to Cucurbituril-Based Molecular Recognition. PMID- 27660884 TI - Transforming growth factor-beta (TGF-beta) activation in cutaneous wounds after topical application of aloe vera gel. AB - Aloe vera is a medicinal plant used to treat various skin diseases. The effects of using aloe vera gel on the healing process were investigated by microscopic methods, cell counting, and TGF-beta gene expression in the wound bed. Sixty Wistar rats weighing 200-250 g were placed under anesthesia in sterile conditions. A square 1.5 cm * 1.5 cm wound was made on the back of the neck. The rats were divided into control and 2 experimental groups. Additionally, the control and experimental groups were separated into 3 subgroups corresponding to 4, 7, and 14 days of study. In the first experimental group, aloe vera was used twice on the wound. The second experimental group received aloe vera overtreatment once on the wound. The positive control group received daily application of 1% phenytoein cream following surgical wound creation. The control group did not receive any treatment. This tissue was examined using histological staining (H&E) and Masson's Trichrome. Wound surface and wound healing were evaluated separately. TGF-beta gene expression was analyzed by RT-PCR. Results showed that fibroblasts in both experimental groups were significantly increased, thereby acceleration wound healing. Application of aloe vera gel will increase TGF-beta gene expression, ultimately accelerating the wound healing process. PMID- 27660885 TI - Strategies for the Total Synthesis of Diverse Bromo-Chamigrenes. AB - Several dozen spirocyclic sesquiterpenoids known as the bromo-chamigrenes have been isolated to date. Yet, despite their unique structures, synthetic efforts toward this collection have been modest. Herein, we outline two strategies to generate their skeletons based on (1) a biomimetic bromonium-induced polyene cyclization using BDSB (Et2SBr.SbCl5Br) and (2) a Diels-Alder reaction which ultimately delivered four members of the class. In addition, X-ray crystallography reveals that one member has a structure in need of revision. PMID- 27660887 TI - Metabolic competition as a driver of bacterial population structure. AB - Understanding the processes whereby diversity arises and is maintained in pathogen populations is pivotal for designing disease control interventions. A particular problem is the maintenance of strain structure in bacterial pathogen populations despite frequent genetic exchange. Although several theoretical frameworks have been put forward to explain this widespread phenomenon, few have focused on the role of genes encoding metabolic functions, despite an increasing recognition of their importance in pathogenesis and transmission. In this article, we review the literature for evidence of metabolic niches within the host and discuss theoretical frameworks which examine ecological interactions between metabolic genes. We contend that metabolic competition is an important phenomenon which contributes to the maintenance of population structure and diversity of many bacterial pathogens. PMID- 27660888 TI - Influence of Surface Energy on Organic Alloy Formation in Ternary Blend Solar Cells Based on Two Donor Polymers. AB - The compositional dependence of the open-circuit voltage (Voc) in ternary blend bulk heterojunction (BHJ) solar cells is correlated with the miscibility of polymers, which may be influenced by a number of attributes, including crystallinity, the random copolymer effect, or surface energy. Four ternary blend systems featuring poly(3-hexylthiophene-co-3-(2-ethylhexyl)thiophene) (P3HT75-co EHT25), poly(3-hexylthiophene-co-(hexyl-3-carboxylate)), herein referred to as poly(3-hexylthiophene-co-3-hexylesterthiophene) (P3HT50-co-3HET50), poly(3 hexylthiophene-thiophene-diketopyrrolopyrrole) (P3HTT-DPP-10%), and an analog of P3HTT-DPP-10% with 40% of 3-hexylthiophene exchanged for 2-(2 methoxyethoxy)ethylthiophen-2-yl (3MEO-T) (featuring an electronically decoupled oligoether side-chain), referred to as P3HTTDPP-MEO40%, are explored in this work. All four polymers are semicrystalline and rich in rr-P3HT content and perform well in binary devices with PC61BM. Except for P3HTTDPP-MEO40%, all polymers exhibit similar surface energies (~21-22 mN/m). P3HTTDPP-MEO40% exhibits an elevated surface energy of around 26 mN/m. As a result, despite the similar optoelectronic properties and binary solar cell performance of P3HTTDPP-MEO40% compared to P3HTT-DPP-10%, the former exhibits a pinned Voc in two different sets of ternary blend devices. This is a stark contrast to previous rr-P3HT-based systems and demonstrates that surface energy, and its influence on miscibility, plays a critical role in the formation of organic alloys and can supersede the influence of crystallinity, the random copolymer effect, similar backbone structures, and HOMO/LUMO considerations. Therefore, we confirm surface energy compatibility as a figure-of-merit for predicting the compositional dependence of the Voc in ternary blend solar cells and highlight the importance of polymer miscibility in organic alloy formation. PMID- 27660886 TI - Benefits of Bifidobacterium animalis subsp. lactis Probiotic in Experimental Periodontitis. AB - BACKGROUND: This study evaluates effects of topical administration of probiotic bacteria of the genus Bifidobacterium on experimental periodontitis (EP) in rats. METHODS: Thirty-two rats were divided into groups C (control; without EP), EP (EP only), C-HN019 (control+probiotic), and EP-HN019 (EP+probiotic). On day 0 of the experiment, animals of groups EP and EP-HN019 received cotton ligatures around mandibular first molars (MFMs). In groups C-HN019 and EP-HN019, 1 mL of suspensions containing Bifidobacterium animalis subsp. lactis (B. lactis) HN019 was topically administered in the subgingival region of MFMs on days 0, 3, and 7. In groups C and EP, topical administrations were performed using a sham suspension (without probiotic). All animals were euthanized at day 14. Gingival tissue, hemimandibles, and oral biofilm were collected. Data were statistically analyzed (P <0.05). RESULTS: Group EP presented greater bone porosity, trabecular separation, and connective tissue attachment loss (CTAL) as well as reduced bone volume than all other groups (P <0.05). In group EP-HN019, there were greater proportions of Actinomyces and Streptococcus-like species and lower proportions of Veillonella parvula, Capnocytophaga sputigena, Eikenella corrodens, and Prevotella intermedia-like species than group EP. Group EP-HN019 presented greater expressions of osteoprotegerin and beta-defensins than group EP (P <0.05). Group EP presented greater levels of interleukin-1beta and receptor activator of nuclear factor-kappa B ligand than group EP-HN019 (P <0.05). CONCLUSION: Topical use of B. lactis HN019 promotes a protective effect against alveolar bone loss and CTALs attributable to EP in rats, modifying immunoinflammatory and microbiologic parameters. PMID- 27660889 TI - MINFIT: A Spreadsheet-Based Tool for Parameter Estimation in an Equilibrium Speciation Software Program. AB - Deterpmination of equilibrium constants describing chemical reactions in the aqueous phase and at solid-water interface relies on inverse modeling and parameter estimation. Although there are existing tools available, the steep learning curve prevents the wider community of environmental engineers and chemists to adopt those tools. Stemming from classical chemical equilibrium codes, MINEQL+ has been one of the most widely used chemical equilibrium software programs. We developed a spreadsheet-based tool, which we are calling MINFIT, that interacts with MINEQL+ to perform parameter estimations that optimize model fits to experimental data sets. MINFIT enables automatic and convenient screening of a large number of parameter sets toward the optimal solutions by calling MINEQL+ to perform iterative forward calculations following either exhaustive equidistant grid search or randomized search algorithms. The combined use of the two algorithms can securely guide the searches for the global optima. We developed interactive interfaces so that the optimization processes are transparent. Benchmark examples including both aqueous and surface complexation problems illustrate the parameter estimation and associated sensitivity analysis. MINFIT is accessible at http://minfit.strikingly.com . PMID- 27660890 TI - What is the degree of innovation routinely implemented in Dutch radiotherapy centres? A multicentre cross-sectional study. AB - OBJECTIVE: To study the implementation of innovation activities in Dutch radiotherapy (RT) centres in a broad sense (product, technological, market and organizational innovations). METHODS: A descriptive cross-sectional study was conducted in 15 Dutch RT centres. A list of innovations implemented from 2011 to 2013 was drawn up for each centre using semi-structured interviews. These innovations were classified into innovation categories according to previously defined innovation indicators. Where applicable, each innovation was rated by each centre on the effort required to implement it and on its expected effects, to get an impression of how far reaching and radical the innovations were and to be able to compare the number of innovations between centres. RESULTS: The participating RT centres in the Netherlands implemented 12 innovations per year on average (range 5-25); this number was not significantly different for academic (n = 13) or non-academic centres (n = 10). Several centres were dealing with the same innovations at the same time. The average required effort and expected output did not differ significantly between product, technological and organizational innovation or between academic and non-academic centres. CONCLUSION: The number of innovations observed per centre varied across a large range, with a large overlap in terms of the type of innovations that were implemented. Registering innovations using the innovation indicators applied in our study would make it possible to improve collaboration between centres, e.g. with common training modules, to avoid duplication of work. Advances in knowledge: This study is the first of its kind investigating innovation implementation in RT in a broad sense. PMID- 27660891 TI - The increasingly anti-tumor effect of a colonic carcinoma DNA vaccine carrying HER2 by the adjuvanticity of IL-12. AB - The present study aimed to determine the effect of recombinant DNA vaccine-based human epidermal growth factor receptor-2 (HER2) and Interleukin 12 (IL-12) on the development of colonic carcinoma in mice and the potential immune mechanisms involved. Recombinant plasmids pVAX1-HER2, pVAX1-IL-12 and pVAX1-HER2-IL-12 were constructed, and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model with a HER2-expressing tumor was designed. Mice vaccinated with the HER2-IL-12 plasmid generated the strongest inhibition efficacy on the growth of HER2-expressing tumors and prolonged mouse survival. These observations emphasized the potential of IL-12 as an adjuvant for DNA vaccines and of vaccines based on HER2 and IL-12 as a promising treatment for colonic carcinoma. PMID- 27660892 TI - Enantioselective Michael Addition of Malonates to Chalcone Derivatives Catalyzed by Dipeptide-derived Multifunctional Phosphonium Salts. AB - Highly enantioselective Michael addition of malonates to enones catalyzed by dipeptide-derived multifunctional phosphonium salts has been developed. The newly established catalytic system was characterized with its wide substrate scope featured with aliphatic aldehyde-derived enones and substituted malonates. The gram scale-up synthesis of adducts can also be successfully achieved under optimal conditions with both excellent yield and enantioselectivity. PMID- 27660893 TI - Stability of isolated antibody-antigen complexes as a predictive tool for selecting toxin neutralizing antibodies. AB - Ricin is an A-B ribosome inactivating protein (RIP) toxin composed of an A-chain subunit (RTA) that contains a catalytic N-glycosidase and a B-chain (RTB) lectin domain that binds cell surface glycans. Ricin exploits retrograde transport to enter into the Golgi and the endoplasmic reticulum, and then dislocates into the cytoplasm where it can reach its substrate, the rRNA. A subset of isolated antibodies (Abs) raised against the RTA subunit protect against ricin intoxication, and RTA-based vaccine immunogens have been shown to provide long lasting protective immunity against the holotoxin. Anti-RTA Abs are unlikely to cross a membrane and reach the cytoplasm to inhibit the enzymatic activity of the A-chain. Moreover, there is not a strict correlation between the apparent binding affinity (Ka) of anti-RTA Abs and their ability to successfully neutralize ricin toxicity. Some anti-RTA antibodies are toxin-neutralizing, whereas others are not. We hypothesize that neutralizing anti-RTA Abs may interfere selectively with conformational change(s) or partial unfolding required for toxin internalization. To test this hypothesis, we measured the melting temperatures (Tm) of neutralizing single-domain Ab (sdAb)-antigen (Ag) complexes relative to the Tm of the free antigen (Tm-shift = Tmcomplex - TmAg), and observed increases in the Tmcomplex of 9-20 degrees. In contrast, non-neutralizing sdAb-Ag complexes shifted the TmComplex by only 6-7 degrees. A strong linear correlation (r2 = 0.992) was observed between the magnitude of the Tm-shift and the viability of living cells treated with the sdAb and ricin holotoxin. The Tm-shift of the sdAb Ag complex provided a quantitative biophysical parameter that could be used to predict and rank-order the toxin-neutralizing activities of Abs. We determined the first structure of an sdAb-RTA1-33/44-198 complex, and examined other sdAb RTA complexes. We found that neutralizing sdAb bound to regions involved in the early stages of unfolding. These Abs likely interfere with steps preceding or following endocytosis that require conformational changes. This method may have utility for the characterization or rapid screening of other Ab that act to prevent conformational changes or unfolding as part of their mechanism of action. PMID- 27660894 TI - Association of CLOCK, ARNTL, PER2, and GNB3 polymorphisms with diurnal preference in a Korean population. AB - Polymorphisms in human circadian genes are potential genetic markers that affect diurnal preference in several populations. In this study, we evaluated whether four polymorphisms in circadian genes CLOCK, ARNTL, PER2, and GNB3 were associated with diurnal preference in a Korean population. In all, 499 healthy subjects were genotyped for four functional polymorphisms in CLOCK, ARNTL, PER2, and GNB3. Composite scale of morningness (CSM) was applied to measure phenotype patterns of human diurnal preference. In addition, three subscale scores, i.e. "morningness," "activity planning," and "morning alertness," were extracted from the CSM. No significant associations were observed between CSM scores and CLOCK (rs1801260) genotype or T allele carrier status, CSM scores and ARNTL (rs2278749) C allele carrier status, and CSM scores and GNB3 (rs5443) genotype or C allele carrier status. However, total CSM scores and scores of its subscales were significantly associated with PER2 (rs934945) genotype (p = 0.010, p = 0.018, and p = 0.005 for total, morningness, and activity planning, respectively) and G allele carrier status (p = 0.003, p = 0.005, and p = 0.002 for total, morningness, and activity planning, respectively). The best model result obtained by performing multifactor dimensionality reduction analysis ([Formula: see text]2 = 11.2798, p = 0.0008) indicated that interaction among C/T single nucleotide polymorphism (SNP) in ARNTL, C/T SNP in GNB3, and G/A SNP in PER2 synergistically affected the risk associated with diurnal preference toward eveningness. These results suggest that circadian gene PER2 is associated with diurnal preference in healthy Korean population. Although polymorphisms in ARNTL and GNB3 were not significantly associated with diurnal preference, their interactions with the polymorphism in PER2 may synergistically increase the risk of diurnal preference toward eveningness. PMID- 27660896 TI - Relevance of Quality Measurement to Integrative Healthcare in the United States. AB - With the advent of new models for payment and delivery of healthcare services, the use of quality measures for continual improvement of clinical healthcare is now an integral feature of medical practice in the United States. However, quality measurement and quality improvement activities are not common practice among integrative health providers. This article discusses the import and application of quality measurement to the practice of integrative healthcare. It reviews developments in the healthcare quality improvement movement, explores the relevance of quality measures to integrative healthcare, describes examples of the current use of quality measures in integrative health practice, discusses discriminatory policies that may prevent participation in quality improvement by integrative health practitioners, and makes recommendations for practice and policy. PMID- 27660897 TI - Feasibility Testing of a Self-Management Program Book to Improve Adherence to PAP in Persons Newly Diagnosed With Sleep Apnea. AB - OBJECTIVES: To obtain feasibility data on a self-management program to improve adherence with positive airway pressure (PAP) in individuals with newly diagnosed obstructive sleep apnea. METHODS: A mixed-methods design assessed program effectiveness and participants' opinions on program ease-of-use. Structured interviews with the treatment group occurred one week and one month after initiation of PAP therapy. RESULTS: Participants (n = 14) completing the study demonstrated 64% adherence versus 58% of the controls. Ease of use was demonstrated. CONCLUSIONS: The PAP self-management program demonstrated ease of use and was found somewhat effective in improving PAP adherence. PRACTICE IMPLICATIONS: The book was useful in assisting participants by validating information obtained from their providers and developing an understanding of the consequences of not using PAP. PMID- 27660898 TI - Senseless Violence Against Central American Unaccompanied Minors: Historical Background and Call for Help. AB - The southwestern U.S. border has recently seen a significant increase in the number of unaccompanied children from Honduras, Guatemala, and El Salvador illegally crossing the Mexican border into the United States. Many of these children leave home to flee violence, starvation, impoverished living conditions, or other life-threatening situations. The treatment of acute stress, anxiety, and depression associated with traumatic events is crucial in helping these children address these negative psychological events they have experienced so that they can move forward with their lives. Untreated, traumatic events experienced by this population can develop into Post Traumatic Stress Disorder, a potentially life-changing and physically threatening psychological and medical issue. The United States needs to effectively address the serious matter of responding to mental health issues facing refugees from war-torn or impoverished nations so as to help them to successfully adjust to American systems. There is a need for researchers in the mental health field to focus efforts in designing, implementing, and evaluating methodologies that can help these children develop healthy strategies for living with a very difficult and complex past. PMID- 27660899 TI - Transplant Survival After Berlin Heart EXCOR Support. AB - The Berlin Heart EXCOR pediatric ventricular assist device (VAD) is approved by the Food and Drug Administration for bridge to cardiac transplantation (BTT) in children. As the clinical outcomes of the EXCOR continue to be evaluated in the United States, data on post-transplant survival are needed. The UNOS database was used to identify patients <18 years old undergoing orthotopic heart transplantation (OHT) from June 2004 to June 2014. Patients undergoing BTT with the EXCOR were identified. A matched cohort of (358) patients undergoing OHT without pretransplant mechanical circulatory support (no-MCS) was also identified as control subjects. The post-transplant survival between the two groups was compared. There were 2,885 pediatric OHT during the study period. Of these, 358 (50%) patients were BTT with the EXCOR. At time of listing, inotrope use was 51.7% vs. 53.4%, (p = 0.653) in the EXCOR cohort and the no-MCS cohort, respectively. At the time of transplantation, end-organ function was equivalent with same median creatinine levels (0.4, p = 0.203) and median total bilirubin (0.5, p = 0.682) for the EXCOR and the no-MCS cohorts. Kaplan-Meier post transplantation survival did not differ between the two cohorts (30 day, 1 year, and 5 year post-transplant survival was 94%, 90%, and 72% [EXCOR cohort] vs. 98%, 91%, and 77% [no-MCS cohort]; p = 0.160). Short- and mid-term post-transplant survival using the EXCOR Pediatric VAD as a BTT in children is equivalent to patients who underwent OHT without pretransplant MCS. PMID- 27660895 TI - Pro- and anti-inflammatory cytokines in cutaneous leishmaniasis: a review. AB - Cutaneous leishmaniasis (CL) is caused by different species of the genus Leishmania. Pro- and anti-inflammatory cytokines play different roles in resistance/susceptibility and the immunopathogenesis of Leishmania infection. The balance and dynamic changes in cytokines may control or predict clinical outcome. T helper 1 (Th1) inflammatory cytokines (especially interferon-gamma, tumor necrosis factor-alpha and interleukin-12) are the crucial factors in the initiation of protective immunity against L. major infection, whereas T helper 2 cytokines including IL-5, IL-4, and IL-13 facilitate the persistence of parasites by downregulating the Th1 immune response. On the other hand, aggravation of inflammatory reactions leads to collateral tissue damage and formation of ulcer. For this reason, immunity system such as T regulatory cells produce regulatory cytokines such as transforming growth factor-beta and IL-10 to inhibit possible injures caused by increased inflammatory responses in infection site. In this article, we review the role of pro- and anti-inflammatory cytokines in the immunoprotection and immunopathology of CL. PMID- 27660901 TI - Multi-Sense CardioPatch: A Wearable Patch for Remote Monitoring of Electro Mechanical Cardiac Activity. AB - This study describes the conceptual design and the first prototype implementation of the Multi-Sense CardioPatch, a wearable multi-sensor patch for remote heart monitoring aimed at providing a more detailed and comprehensive heart status diagnostics. The system integrates multiple sensors in a single patch for detection of both electrical (electrocardiogram, ECG) and mechanical (heart sounds, HS) cardiac activity, in addition to physical activity (PA). The prototypal system also comprises a microcontroller board with a radio communication unit and it is powered by a Li-Ion rechargeable battery. Results from preliminary evaluations on healthy subjects have shown that the prototype can successfully measure electro-mechanical cardiac activity, providing useful cardiac indexes. The system has potential to improve remote monitoring of cardiac function in chronically diseased patients undergoing home-based cardiac rehabilitation programs. PMID- 27660900 TI - Is Stopping Heparin Safe in Patients on Extracorporeal Membrane Oxygenation Treatment? AB - Anticoagulation treatment during extracorporeal membrane oxygenation (ECMO) treatment is unavoidable. However, discontinuation of heparin infusion is necessary when challenges associated with the use of heparin, such as bleeding and thrombocytopenia, are encountered. The medical records of 94 adult (age >= 18 years) patients treated with ECMO from January 2011 to March 2015, at Chung-Ang University Hospital, Seoul, Korea, were reviewed. Among the 94 patients, 55 patients underwent ECMO treatment for three or more days. In 52.7% of these patients (n = 29, group A), heparin was stopped for three or more days because of thrombocytopenic events (< 50,000 cells/mm), higher than target range (> 230 seconds) activated clotting time (ACT), bleeding complications, or the need for other surgical procedures. In 43.6% of patients (n = 24, group B), heparin was continuously infused during the entire ECMO process. The mean length of ECMO support after the initiation of heparin discontinuation in patients in group A was 10.2 +/- 14.7 days. There were no intracardiac, intravascular, or intracircuit thrombotic complications in group A. There was no difference in the ECMO weaning success rate between the two groups (41.4% in group A vs. 54.2% in group B, p = 0.353). Heparin discontinuation can be considered in a select group of patients with coagulation abnormalities or bleeding. PMID- 27660902 TI - Role of Thromboelastography Platelet Mapping and International Normalized Ratio in Defining "Normocoagulability" During Anticoagulation for Mechanical Circulatory Support Devices: A Pilot Retrospective Study. AB - Thromboembolic (TE) events and hemorrhagic complications continue to remain as frequent adverse events and causes of death after mechanical circulatory support device (MCSD) implantation. To counterbalance this postimplant multifactorial hypercoagulable state, antithrombotic therapy given postimplant must be individually tailored to keep patient adequately anticoagulated yet normocoagulable. Prior studies describing different anticoagulation protocols do not define normocoagulability for patients on MCSDs. We evaluated the role of thromboelastography platelet mapping (TEG PM) in defining "normocoagulability" for MCS patients on anticoagulant (warfarin) and antiplatelet agents. Ninety eight MCSD patients who underwent TEG PM assay at our institution from 2012 to 2014 were included for retrospective analysis. Eleven (11.2%) subjects developed at least one TE event during the study period. Of the 13 TE events, 8 occurred in patients with total artificial heart (TAH). TEG parameters closest to the event or when patient was clinically adequately anticoagulated and corresponding international normalized ratio (INR) were measured. Thromboelastography coagulation index (CI) appears to be the single most statistically significant parameter that can be used to designate a patient as normocoagulable. Based on our results, patients with HeartMate II (HM II) and Heart Ware (HW) devices should be maintained at a CI value of less than or equal to 1.5 whereas patients with TAH devices should be maintained at a CI less than or equal to 1.2. The CI should be correlated with the degree of Vitamin K-dependent coagulation factor inhibition that is achieved using device-specific goal INR ranges. A recent modification, TEG PM assesses the effects of antiplatelet drug. Maximal amplitude arachidonic acid (MA-AA) < 50 and maximal amplitude adenosine diphosphate (MA ADP) < 50 are desired for normocoagulable state. PMID- 27660903 TI - CRRT Connected to ECMO: Managing High Pressures. AB - Metabolic disorders and fluid overload are indications of continuous renal replacement therapy (CRRT) including continuous venovenous hemofiltration in patients on extracorporeal membrane oxygenation (ECMO). Direct connection of CRRT machine to the ECMO circuit provides many advantages. Nevertheless, because pressures in CRRT lines relate to ECMO blood flow, high ECMO blood flow may be associated with high pressures in CRRT lines. Thus, management of CRRT pressure lines becomes challenging. We evaluated a protocol for managing high CRRT pressures. Connections were performed according to a standardized protocol to maintain CRRT lines in the correct pressure ranges without modifying ECMO settings or inhibiting pressure alarms. To achieve this goal, the way of connecting of CRRT lines was adapted following a standardized protocol. Connection was first attempted between pump and oxygenator in the 12 patients. In five cases, high pressures in CRRT lines were successfully managed by changing the connection segment. Continuous renal replacement therapy parameters were within target levels and reduction of serum creatinine was 37%. In conclusion, management of high pressures in CRRT lines induced by ECMO could be achieved without modifying ECMO blood flow or inhibiting CRRT alarms. Iterative stops were avoided allowing efficient procedures. PMID- 27660904 TI - Cannula Design and Recirculation During Venovenous Extracorporeal Membrane Oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is used as a lifesaving rescue treatment in refractory respiratory or cardiac failure. During venovenous (VV) ECMO, the presence of recirculation is known, but quantification and actions to minimize recirculation after measurement are to date not routinely practiced. In the current study, we investigated the effect of draining cannula design on recirculation fraction (Rf) during VV ECMO; conventional mesh cannula was compared with a multistage cannula. The effect of adjusting cannula position was also studied. Recirculation was measured with ultrasound dilution technique at different ECMO flows and after cannula repositioning. All patients who were admitted to our unit between October 2014 and July 2015 catheterized by the atrio femoral single lumen method were included. A total of 108 measurements were conducted in 14 patients. The multistage cannula showed significantly less recirculation (19.0 +/- 12.2%) compared with the conventional design (38.0 +/- 13.7). Pooled data in cases improved from adjustment showing reduced Rf by 7%. In conclusion, the choice of cannula matters, as does adjustment of the draining cannula position during atrio-femoral VV ECMO. By utilizing the ultrasound dilution technique to measure Rf before and after repositioning, effective ECMO flow can be improved for a more effective ECMO treatment. PMID- 27660905 TI - Sources of Circuit Thrombosis in Pediatric Extracorporeal Membrane Oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support of critically ill patients is used frequently in the pediatric population. ECMO is burdened by complications, including thrombosis and hemorrhage. Here we demonstrate the focused location of clots, their histologic composition, and the relationship of in situ thrombus to local hemodynamics in ECMO circuits. Pediatric ECMO circuits from Children's Healthcare of Atlanta, Emory University (Atlanta, GA) were obtained after removal from extracorporeal support over a 2.5 year period (n = 50). All clots and material deposited within the circuit were recorded. Location of clot was compared with local hemodynamics. Most clots were adherent to the junctions made by the tubing and connectors, as opposed to being randomly disturbed throughout the circuit tubing (p << 0.05). Loose, nonadherent clots were also found at the entry side of oxygenators. The clots colocated directly with zones of low shear rate. Histology revealed a fibrinous composition, consistent with coagulation potentiated by low shear. Centrifugal pump circuits (n = 16) had more clots than roller pump (n = 34) circuits (p << 0.05). In addition, all centrifugal pumps had clots that formed at the top of the pump shaft. The ECMO circuits from our single-center study demonstrate the concentrated location of fibrin clots at low shear zones created by tubing connector junctions. Type of pump also influences the frequency of clot formation. Since the mechanism of the majority of ECMO circuit thrombosis is low shear and fibrin driven, optimization of hemodynamics and anticoagulation regimen may reduce clot formation and bleeding. PMID- 27660906 TI - Heat Generation in Axial and Centrifugal Flow Left Ventricular Assist Devices. AB - Despite increasing use of left ventricular assist devices (LVADs) as a surgical treatment for advanced heart failure in an era of improved outcomes with LVAD support, the mechanical interactions between these pumps and the cardiovascular system are not completely understood. We utilized an in vitro mock circulatory loop to analyze the heat production incurred by operation of an axial flow and centrifugal flow LVAD. A HeartMate II and a HeartWare HVAD were connected to an abbreviated flow loop and were implanted in a viscoelastic gel. Temperature was measured at the surface of each LVAD. Device speed and fluid viscosity were altered and, in the HeartMate II, as artificial thrombi were attached to the inflow stator, impeller, and outflow stator. The surface temperatures of both LVADs increased in all trials and reached a plateau within 80 minutes of flow initiation. Rate of heat generation and maximum system temperature were greater when speed was increased, when viscosity was increased, and when artificial thrombi were attached to the HeartMate II impeller. Normal operation of these two widely utilized LVADs results in appreciable heat generation in vitro. Increased pump loading resulted in more rapid heat generation, which was particularly severe when a large thrombus was attached to the impeller of the HeartMate II. While heat accumulation in vivo is likely minimized by greater dissipation in the blood and soft tissues, focal temperature gains with the pump housing of these two devices during long-term operation may have negative hematological consequences. PMID- 27660907 TI - "Trust the researchers": flying in the face of evidence. AB - There are always rival hypotheses to explain away the one that is posited as the most likely to be true. Context and Occam's razor - the principle that among competing hypotheses, the one with the fewest assumptions should be selected - ultimately point to which hypothesis is the most likely to be true. PMID- 27660908 TI - The quest for the minimal bacterial genome. AB - The onset of techniques for both editing extant bacterial chromosomes and synthesizing long DNA sequences has enabled addressing the question on the smallest set of genes and biological functions that are required for running an operative cell. But this is not only a fundamental scientific endeavour: simpler genomes could be easier to understand and eventually reprogram for the sake of diverse applications. This has fostered efforts to eliminate apparently useless - if not annoying DNA segments from many biotechnologically relevant strains as well as attempts to (re)write complete genomes a la carte. Yet, the smallest number of genes that enable given functionalities do vary depending on the ultimate agenda, as both natural and engineered small-size genomes afford genetic simplicity by engaging in a suite of complex interactions with the surrounding medium. PMID- 27660909 TI - Copolymer Brushes with Temperature-Triggered, Reversibly Switchable Bactericidal and Antifouling Properties for Biomaterial Surfaces. AB - The adherence of bacteria and the formation of biofilm on implants is a serious problem that often leads to implant failure. A series of antimicrobial coatings have been constructed to resist bacterial adherence or to kill bacteria through contact with or release of antibacterial agents. The accumulation of dead bacteria facilitates further bacterial contamination and biofilm development. Herein, we have designed and constructed a novel, reversibly switchable bactericidal and antifouling surface through surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization to combine thermally responsive N-isopropylacrylamide (NIPAAm) and bactericidal quaternary ammonium salts (2-(dimethylamino)-ethyl methacrylate (DMAEMA+)). Measurements of spectroscopic ellipsometry and water contact angle and X-ray photoelectron spectroscopy were used to examine the process of the surface functionalization. The temperature-responsive P(DMAEMA+-co-NIPAAm) copolymer coating can switch by phase transition between a hydrophobic capturing surface at high temperatures and a relatively hydrophilic antifouling surface at lower temperatures. The quaternary ammonium salts of PDMAEMA+ displayed bactericidal efficiency against both Escherichia coli and Staphylococcus aureus. The functionalized surface could efficiently prevent bovine serum albumin adsorption and had good biocompatibility against human lens epithelial cells. PMID- 27660910 TI - Interaction between gene repair and mobile elements-induced activity systems after low-dose irradiation. AB - PURPOSE: To analyze the role of mus-genes repair in system activation P-elements in Drosophila melanogaster induced by a chronic exposure to low doses. MATERIALS AND METHODS: The materials were dysgenic individuals of Drosophila melanogaster with mutations in repair genes (mus101, mus205, mus304, mus308, mus309) and simultaneous transposition of mobile P-elements. The animals were exposed to a chronic irradiation in low doses (0.42 mGy/h). The reaction of animals was analyzed by the DNA damage rate in somatic cells ('Comet assay'), level of dominant lethal mutations, fecundity, and survival rate. RESULTS: The combined action of the systems of post-replication, recombination repair (mus205, mus304), repair of DNA double-stranded breaks (mus304), and of the transposition activity of P-elements after a chronic irradiation in low doses was identified according to every study parameter. The other repair systems and their genes (mus101, mus308, and mus309) responded to action of only one factor (irradiation or mobile elements transposition). CONCLUSION: The obtained data significantly contribute to the knowledge on a new reaction of the mechanisms of organisms to a chronic irradiation in low doses. PMID- 27660911 TI - Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation. AB - PURPOSE: To evaluate the enhancement effect of two combined radiation-sensitizing agents in mammalian cells at small doses as compared to large doses using the linear-quadratic (LQ) mathematical model. METHODS AND MATERIALS: Data on clonogenic assays concerning the radio-enhancement effects of combined halogenated pyrimidines and hyperthermia or combined cisplatin and hyperthermia, as published in earlier reports, were analyzed according to the LQ-formula: S(D)/S(0) = exp-(alphaD + betaD(2)). Effects of sensitizing agents on the linear parameter alpha and the quadratic parameter beta are compared in order to evaluate differences depending on the applied dose, the possible relations to mechanisms of radiation sensitization and to derive suggestions for applications. RESULTS: The values of the linear parameter alpha, which determines the effectiveness at low doses, are for all cell lines and all conditions more increased than the values of the parameter beta which has a higher contribution at larger radiation doses. The combination of hyperthermia with halogenated pyrimidines to radiation as well as the combination of hyperthermia and cisplatin to radiation significantly increases the value of the linear parameter alpha, as compared to radiation alone or radiation combined with a single agent. CONCLUSIONS: The radiation enhancement factors of the values of linear and quadratic parameters demonstrate that the sensitizing agents have a larger effect on the linear parameter which is dominant at low radiation doses as is used in fractionated-radiation treatment in the clinic. Moreover, the effect is even further increased when two radiation sensitizers are used. PMID- 27660913 TI - The Presence of New Psychoactive Substances in a Tor Network Marketplace Environment. AB - Prior research has documented the availability of drugs on many Tor Network websites, with the Internet playing a particularly vital role in the global new psychoactive substances (NPS) market. The primary objective of this research was to document types of NPS for sale on the largest operating Tor site (Agora) over a period of four months. Secondary objectives were to analyze countries and vendors sourcing NPS on Agora. Data from Agora were collected in February and June 2015. The number of total advertisements on Agora increased from 20,742 to 27,431 over the four months, while the number of NPS advertisements increased from 2,205 to 2,271 and the number of vendors increased from 157 to 288. The composition of NPS listings and source countries for NPS advertised on Agora diversified over time. Advertisements for ketamine and unclassified NPS experienced substantial growth, while the availability of phenethylamines decreased. However, phenethylamines remained the most frequently advertised NPS type. China and the U.S. were found to be the top two countries by volume selling NPS on Agora over the fpir months, but the number of countries identified as advertising NPS increased by nearly 43%. The United States housed the most NPS vendors. PMID- 27660914 TI - Model-based screening for critical wet-weather discharges related to micropollutants from urban areas. AB - Wet-weather discharges contribute to anthropogenic micropollutant loads entering the aquatic environment. Thousands of wet-weather discharges exist in Swiss sewer systems, and we do not have the capacity to monitor them all. We consequently propose a model-based approach designed to identify critical discharge points in order to support effective monitoring. We applied a dynamic substance flow model to four substances representing different entry routes: indoor (Triclosan, Mecoprop, Copper) as well as rainfall-mobilized (Glyphosate, Mecoprop, Copper) inputs. The accumulation on different urban land-use surfaces in dry weather and subsequent substance-specific wash-off is taken into account. For evaluation, we use a conservative screening approach to detect critical discharge points. This approach considers only local dilution generated onsite from natural, unpolluted areas, i.e. excluding upstream dilution. Despite our conservative assumptions, we find that the environmental quality standards for Glyphosate and Mecoprop are not exceeded during any 10-min time interval over a representative one-year simulation period for all 2500 Swiss municipalities. In contrast, the environmental quality standard is exceeded during at least 20% of the discharge time at 83% of all modelled discharge points for Copper and at 71% for Triclosan. For Copper, this corresponds to a total median duration of approximately 19 days per year. For Triclosan, discharged only via combined sewer overflows, this means a median duration of approximately 10 days per year. In general, stormwater outlets contribute more to the calculated effect than combined sewer overflows for rainfall-mobilized substances. We further evaluate the Urban Index (Aurban,impervious/Anatural) as a proxy for critical discharge points: catchments where Triclosan and Copper exceed the corresponding environmental quality standard often have an Urban Index >0.03. A dynamic substance flow analysis allows us to identify the most critical discharge points to be prioritized for more detailed analyses and monitoring. This forms a basis for the efficient mitigation of pollution. PMID- 27660915 TI - FAR-RED ELONGATED HYPOCOTYL3 promotes floral meristem determinacy in Arabidopsis. AB - The transposase-derived transcription factor genes FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED IMPAIRED RESPONSE1 (FAR1) have redundant and multifaceted roles in plant growth and development during the vegetative stage, including phytochrome A-mediated far-red light (FR) signaling and circadian clock entrainment. Little is known about their functions in the reproductive stage. We recently demonstrated that FHY3 plays important roles in shoot apical meristem (SAM) maintenance and floral meristem (FM) determinacy through its target genes CLAVATA3 (CLV3), SEPALLATA1 (SEP1) and SEP2. Here we present data that FHY3 but not its homolog, FAR1, has a distinct role in FM determinacy in a manner independent of its light signaling and circadian pathway functions. Moreover, genome-wide gene expression profiling showed that the homeostasis of the FM is critical for the regulation of FM activity. PMID- 27660916 TI - Upsurge of Enterovirus D68, the Netherlands, 2016. AB - In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3. PMID- 27660918 TI - Pharmacogenetic study focused on fluoxetine pharmacodynamics in children and adolescent patients: impact of the serotonin pathway. AB - OBJECTIVE: Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics. PATIENTS AND METHODS: The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways. RESULTS: Clinical improvement after treatment with fluoxetine in our pediatric population was associated significantly with two polymorphisms located in genes related to the serotonergic system: the 5-hydroxytryptamine receptor 1B (HTR1B) and the tryptophan 5-hydroxylase 2 (TPH2). CONCLUSION: Although a wide range of candidate genes related to different pathways were assessed, the results show that genetic markers directly related to serotonin have an important effect on fluoxetine response. PMID- 27660917 TI - Postdischarge Falls and Readmissions: Associations with Insufficient Vision and Low Health Literacy among Hospitalized Seniors. AB - The role of patient-level risk factors such as insufficient vision has been understudied. Because insufficient vision may interfere with health literacy assessments, the full impact of low health literacy among older patients with impaired vision is unknown. We sought to determine whether senior inpatients' insufficient vision and low health literacy are associated with adverse outcomes postdischarge, specifically falls and readmissions. We conducted an observational study of adult medicine inpatients at an urban hospital. Visual acuity and health literacy were screened at bedside. Outcomes data were collected by telephone 30 days postdischarge. Among 1,900 participants, 1,244 (65%) were reached postdischarge; 44% had insufficient vision and 43% had low health literacy. Insufficient vision was associated with postdischarge falls among participants >=65 years (adjusted odds ratio [AOR] 3.38, 95% confidence interval [CI] 1.42 8.05), but not among participants <65 years (AOR 1.44, 95% CI 0.89-2.32). Low health literacy was associated with readmissions among participants >=65 years (AOR 3.15, 95% CI 1.77-5.61), but not among participants <65 years (AOR 0.78, 95% CI 0.56-1.09). The results suggest the need to implement screening for older inpatients' vision and health literacy. Developing effective interventions to reduce these risks is critical given national priorities to reduce falls and readmissions. PMID- 27660919 TI - Band gap states in nanocrystalline WO3 thin films studied by soft x-ray spectroscopy and optical spectrophotometry. AB - Nanocrystalline tungsten trioxide (WO3) thin films prepared by DC magnetron sputtering have been studied using soft x-ray spectroscopy and optical spectrophotometry. Resonant inelastic x-ray scattering (RIXS) measurements reveal band gap states in sub-stoichiometric gamma-WO3-x with x = 0.001-0.005. The energy positions of these states are in good agreement with recently reported density functional calculations. The results were compared with optical absorption measurements in the near infrared spectral region. An optical absorption peak at 0.74 eV is assigned to intervalence transfer of polarons between W sites. A less prominent peak at energies between 0.96 and 1.16 eV is assigned to electron excitation of oxygen vacancies. The latter results are supported by RIXS measurements, where an energy loss in this energy range was observed, and this suggests that electron transfer processes involving transitions from oxygen vacancy states can be observed in RIXS. Our results have implications for the interpretation of optical properties of WO3, and the optical transitions close to the band gap, which are important in photocatalytic and photoelectrochemical applications. PMID- 27660920 TI - Clinical Performance of a Spherical Hybrid Lens Design in High Regular Astigmatism. AB - OBJECTIVES: To evaluate safety, efficacy, and comfort of a spherical hybrid contact lens design in management of the regular astigmatic cornea. METHODS: This prospective study included 18 eyes from 18 subjects with regular corneal astigmatism greater than -3.00 diopters. All patients were fitted with optimal hybrid contact lenses. Demographic data and fitting parameters were recorded. Patient refraction, visual outcomes, contrast sensitivity, and glare levels were measured 2 weeks, 3 months, and 6 months after the start of lens use. Duration of lens use, comfort grades, causes of lens discontinuation, and any noticed complications were recorded. RESULTS: An average of 1.8 lenses (range 1-3) was required to achieve the optimal fit. Average logMAR visual acuity had improved significantly from 0.92+/-0.03 to 0.03+/-0.04 (P<0.001) at the last follow-up. Contrast sensitivity and glare tests were also significantly improved. Statistical analysis of the subjective responses indicated a strong acceptance of the lens by most of the patients. Mean wearing time of lenses was 10.1+/-3.2 hr/d. Causes of discontinuation were discomfort (2 patients), high lens price (2 patients), and handling problems (1 patient). Minimal complications were demonstrated in wearers of the lenses during follow-up visits. CONCLUSION: Spherical hybrid contact lenses provide a good option for patients with regular astigmatic corneas. They provide optimal visual function with high comfort and patient satisfaction, especially when surgery is undesirable or contraindicated. PMID- 27660921 TI - Dry Eye Assessment in Patients With Vitamin D Deficiency. AB - OBJECTIVES: The aim of this study was to evaluate tear film function in patients with vitamin D deficiency. METHODS: In a single center, 60 eyes of 30 patients with vitamin D deficiency (group 1), and 60 eyes of 30 healthy individuals (group 2) were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear break-up time (TBUT), scoring of ocular surface fluorescein staining using a modified Oxford scale, and tear osmolarity. RESULTS: Tear osmolarity values, OSDI, and Oxford scale scores were significantly higher in group 1 (309+/-9 mOsm/L, 35.78+/-21.44 and 1.3+/-0.9, respectively) compared with group 2 (295+/-10 mOsm/L, 18.69+/-17.21 and 0.4+/-0.8, respectively) (P<0.001 for all). Schirmer I test and TBUT results in group 1 (8.5+/-3.7 mm and 8.7+/-0.6 sec, respectively) were significantly lower compared with group 2 (16.6+/-2.4 and 18.1+/-0.5, respectively) (P<0.001 for all). CONCLUSIONS: This study demonstrates that vitamin D deficiency is associated with tear hyperosmolarity and tear film dysfunction. Patients with vitamin D deficiency may be prone to dry eye. PMID- 27660922 TI - Occupational therapy for delirium management in elderly patients without mechanical ventilation in an intensive care unit: A pilot randomized clinical trial. AB - PURPOSE: Delirium has negative consequences such as increased mortality, hospital expenses and decreased cognitive and functional status. This research aims to determine the impact of occupational therapy intervention in duration, incidence and severity of delirium in elderly patients in the intensive care unit; secondary outcome was to assess functionality at hospital discharge. METHODS: This is a pilot randomized clinical trial of patients without mechanical ventilation for 60 years. Patients were assigned to a control group that received standard strategies of prevention (n=70) or to an experimental group that received standard strategies plus occupational therapy twice a day for 5 days (n=70). Delirium was valued with Confusion Assessment Method and Delirium Rating Scale, and functional outcomes at discharge with Functional Independence Measure, Hand Dynamometer, and Mini-Mental State Examination. RESULTS: A total of 140 participants were recruited. The experimental group had lower duration (risk incidence ratios, 0.15 [P=.000; 95% confidence interval, 0.12-0.19] vs 6.6 [P=.000, 95% confidence interval, 5.23-8.3]) and incidence of delirium (3% vs 20%, P=.001), and had higher scores in Motor Functional Independence Measure (59 vs 40 points, P<.0001), cognitive state (MMSE: 28 vs 26 points, P<.05), and grip strength in the dominant hand (26 vs 18 kg, P<.05), compared with the control group. CONCLUSIONS: Occupational therapy is effective in decreasing duration and incidence of delirium in nonventilated elderly patients in the intensive care unit and improved functionality at discharge. PMID- 27660923 TI - The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials. AB - PURPOSE: Inotropes and vasopressors are cornerstone of therapy in septic shock, but search for the best agent is ongoing. We aimed to determine which vasoactive drug is associated with the best survival. MATERIALS AND METHODS: PubMed, BioMedCentral, Embase, and the Cochrane Central Register were searched. Randomized trials performed in septic patients with at least 1 group allocated to an inotrope/vasopressor were included. Network meta-analysis with a frequentist approach was performed. RESULTS: The 33 included studies randomized 3470 patients to 16 different comparators. As compared with placebo, levosimendan (odds ratio [OR], 0.17, 95%; confidence interval [CI], 0.05-0.60), dobutamine (OR, 0.30; 95% CI, 0.09-0.99), epinephrine (OR, 0.35; 95% CI, 0.13-0.96), vasopressin (OR, 0.37; 95% CI, 0.16-0.89), and norepinephrine plus dobutamine (OR, 0.4; 95% CI, 0.11 0.96) were significantly associated with survival. Norepinephrine improved survival compared with dopamine (OR, 0.81; 95% CI, 0.66-1.00). Rank analysis showed that levosimendan had the highest probability of being the best treatment. CONCLUSIONS: Among several regimens for pharmacological cardiovascular support in septic patients, regimens based on inodilators have the highest probability of improve survival. PMID- 27660924 TI - Sleep in intensive care unit: The role of environment. AB - PURPOSE: To determine if improving intensive care unit (ICU) environment would enhance sleep quality, assessed by polysomnography (PSG), in critically ill mechanically ventilated patients. MATERIALS AND METHODS: Randomized controlled trial, crossover design. The night intervention "quiet routine" protocol was directed toward improving ICU environment between 10pm and 6am. Noise levels during control and intervention nights were recorded. Patients on mechanical ventilation and able to give consent were eligible for the study. We monitored sleep by PSG.The standard (American Association of Sleep Medicine) sleep scoring criteria were insufficient for the assessment of polysomnograms. Modified classification for sleep scoring in critically ill patients, suggested by Watson et al. (Crit Care Med 2013;41:1958-1967), was used. RESULTS: Sound level analysis showed insignificant effect of the intervention on noise reduction (P=.3). The analysis of PSGs revealed that only 53% of the patients had identifiable characteristics of normal sleep, whereas 47% showed only pathologic patterns. CONCLUSIONS: Characteristics of normal sleep were absent in many of the PSG recordings in these critically ill patients. We were not able to further reduce the already existing low noise levels in the ICU and did not find any association between the environmental intervention and the presence of normal sleep characteristics in the PSG. PMID- 27660925 TI - Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen Induced Tumor Formation and Metastasis. AB - Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. Purified AEP protein injected through the tail vein promoted tumor growth and mammary tumor metastasis and shortened survival, whereas AEP-specific small compound inhibitors (AEPIs) effectively suppressed tumor progression and prolonged host survival. Further analysis of the molecular mechanism revealed that AEP was important for PI3K/AKT pathway activation. Thus, an elevated serum AEP level was closely related to mammary cancer progression and metastasis, and AEP is a potential target for breast cancer therapy in the clinic. PMID- 27660926 TI - Altered Biomarkers in Trophoblast Cells Obtained Noninvasively Prior to Clinical Manifestation of Perinatal Disease. AB - A contributing factor to poor placental perfusion, leading to intrauterine growth restriction and preeclampsia, is the failure of invading extravillous trophoblast (EVT) cells to remodel the maternal uterine arteries during the first and second trimesters of pregnancy. Noninvasive assessment of EVT cells in ongoing pregnancies is possible beginning three weeks after conception, using trophoblast retrieval and isolation from the cervix (TRIC). Seven proteins were semi quantified by immunofluorescence microscopy in EVT cells obtained between gestational weeks 6 and 20 from pregnancies with normal outcomes (N = 29) and those with intrauterine growth restriction or preeclampsia (N = 12). Significant differences were measured in expression of PAPPA, FLT1, ENG, AFP, PGF, and LGALS14, but not LGALS13 or the lineage marker KRT7. These findings provide for the first time direct evidence of pathology-associated protein dysregulation in EVT cells during early placentation. The TRIC platform provides a novel approach to acquire molecular signatures of EVT cells that can be correlated with pregnancy outcome. PMID- 27660928 TI - Benign Breast Diseases: Evaluation and Management. AB - Benign breast disease is a spectrum of common disorders. The majority of patients with a clinical breast lesion will have benign process. Management involves symptom control when present, pathologic-based and imaging-based evaluation to distinguish from a malignant process, and counseling for patients that have an increased breast cancer risk due to the benign disorder. PMID- 27660927 TI - Effect of wire fretting on the corrosion resistance of common medical alloys. AB - Metallic medical devices such as intravascular stents can undergo fretting damage in vivo that might increase their susceptibility to pitting corrosion. As a result, the US Food and Drug Administration has recommended that such devices be evaluated for corrosion resistance after the devices have been fatigue tested in situations where significant micromotion can lead to fretting damage. Three common alloys that cardiovascular implants are made from [MP35N cobalt chromium (MP35N), electropolished nitinol (EP NiTi), and 316LVM stainless steel (316LVM)] were selected for this study. In order to evaluate the effect of wire fretting on the pitting corrosion susceptibility of these medical alloys, small and large fretting scar conditions of each alloy fretting against itself, and the other alloys in phosphate buffered saline (PBS) at 37 degrees C were tested per ASTM F2129 and compared against as received or PBS immersed control specimens. Although the general trend observed was that fretting damage significantly lowered the rest potential (Er ) of these specimens (p < 0.01), fretting damage had no significant effect on the breakdown potential (Eb , p > 0.05) and hence did not affect the susceptibility to pitting corrosion. In summary, our results demonstrate that fretting damage in PBS alone is not sufficient to cause increased susceptibility to pitting corrosion in the three common alloys investigated. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2487-2494, 2017. PMID- 27660929 TI - Simulation and Shoulder Dystocia. AB - Shoulder dystocia is an unpredictable obstetric emergency that requires prompt interventions to ensure optimal outcomes. Proper technique is important but difficult to train given the urgent and critical clinical situation. Simulation training for shoulder dystocia allows providers at all levels to practice technical and teamwork skills in a no-risk environment. Programs utilizing simulation training for this emergency have consistently demonstrated improved performance both during practice drills and in actual patients with significantly decreased risks of fetal injury. Given the evidence, simulation training for shoulder dystocia should be conducted at all institutions that provide delivery services. PMID- 27660930 TI - Current Management of the Axilla. AB - Despite advances in estimating prognosis and predicting response to adjuvant systemic therapy, the status of the axillary lymph nodes remains a critical component in initial surgical planning and in determining therapeutic strategies for patients with breast cancer. Buoyed by evidence from multi-institutional randomized clinical trials, the last 2 decades have witnessed remarkable and practice-changing advances in our approach to the axilla. This review concentrates on the current best practice in axillary management for both node negative and node-positive patients, with particular focus on the evolving management of the axilla in the era of neoadjuvant systemic therapy. PMID- 27660931 TI - PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee. AB - OBJECTIVE: The objective of this consensus is to update the recommendations for the treatment of hand, hip, and knee osteoarthritis (OA) by agreeing on key propositions relating to the management of hand, hip, and knee OA, by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America. METHODS: Recommendations were developed by a group of 48 specialists of rheumatologists, members of other medical disciplines (orthopedics and physiatrists), and three patients, one for each location of OA. A systematic review of existing articles, meta-analyses, and guidelines for the management of hand, hip, and knee OA published between 2008 and January 2014 was undertaken. The scores for Level of Evidence and Grade of Recommendation were proposed and fully consented within the committee based on The American Heart Association Evidence-Based Scoring System. The level of agreement was established through a variation of Delphi technique. RESULTS: Both "strong" and "conditional" recommendations are given for management of hand, hip, and knee OA and nonpharmacological, pharmacological, and surgical modalities of treatment are presented according to the different levels of agreement. CONCLUSIONS: These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important. PMID- 27660932 TI - Systemic Lupus Erythematosus Does Not Increase Risk of Adverse Events in the First 6 Months After Total Knee Arthroplasty. AB - BACKGROUND: Increasing numbers of patients with systemic lupus erythematosus (SLE) are undergoing total knee arthroplasty (TKA). Whether postsurgical adverse events (AEs) are higher in patients with SLE than patients with osteoarthritis (OA) is unknown. OBJECTIVES: This study aims to compare AEs within 6 months of TKA. METHODS: Patients in a single institution's arthroplasty and SLE registries who underwent TKA from 2007 to 2014 were eligible. SLE cases were matched 1:2 to OA on age, sex, year of TKA, and procedure type. AEs were collected through chart review and registry responses. Baseline characteristics were compared and regression analysis performed to determine predictors of AEs. RESULTS: Fifty-two SLE TKA were matched to 104 OA TKA. There was no difference in follow-up between groups. SLE patients had more comorbidities (>=1 Charlson-Deyo comorbidity: SLE 38.4% vs. OA 17.3%; P-value < 0.001) and steroid use (preoperative [SLE 28.8% vs. OA 1.9%, P-value < 0.001] and perioperative "stress-dose" [30.8% vs. 2.9%, P value = 0.01]). SLE patients did not experience more major (SLE 25.0% vs. OA 19.2%; P-value = 0.41), minor (15.4% vs. 10.6%; P-value = 0.39), or total (38.5% vs. 27.9%; P-value = 0.18) AEs. AEs were not increased among patients on stress dose steroids. In a multiple logistic regression analysis controlling for comorbidities and diagnosis, neither SLE (OR 1.61, 95% CI 0.74-3.50) nor >1 comorbidity (OR 1.05, 95% CI 0.46-2.39) was an independent risk factor for AEs. CONCLUSION: SLE is not an independent risk factor for increased AEs 6 months after TKA. Stress-dose steroid use does not heighten AE risk. These findings should inform recommendations for SLE patients considering TKA. PMID- 27660933 TI - Detection of Anti-Type II Collagen Antibodies in Patients With Chronic Gouty Arthritis: Findings From a Pilot Study. AB - OBJECTIVE: We hypothesized that chronic gouty arthritis patients would develop an immune response to type II collagen that would be revealed by the presence of anti-type II collagen (CII) antibodies in serum, which may in turn be involved in progression to non-remitting arthritis. METHODS: Chronic gouty arthritis was defined as crystal-confirmed gout in patients with no pain-free intercritical period, with or without the presence of tophi, who did not have clinical features of other forms of chronic arthritis. Age-matched gout patients suffering acute gouty attacks who had definite intercritical periods were selected as a control group. Four RA patients who had active disease were enrolled as a positive control group. Anti-CII antibodies were quantified in patient sera via ELISA using a human IgG anti-CII antibody assay kit. Correlations between anti-CII levels and clinical parameters were sought. RESULTS: Fifteen chronic gouty arthritis patients were identified. The anti-CII level was significantly higher among subjects with chronic gout compared to controls, but did not significantly differ in control gout patients during acute attacks and in the intercritical periods. Five patients with chronic gouty arthritis had anti-CII antibody levels higher than 200 AU/mL, whereas only one control gout patient exhibited this feature. Two of four patients with active RA had anti-CII antibody levels higher than 200 U/mL.Patients with tophi had significantly higher anti-CII levels than those without, whereas patients showing radiographic erosion tended to have higher anti-CII levels than those without. CONCLUSION: Patients with chronic gouty arthritis had significantly higher levels of anti-CII antibodies than control gout patients. Such antibody production would be triggered by initiation of cartilage damage but may also play a role in perpetuation of inflammation. PMID- 27660935 TI - Detection of Calcium Crystals in Knee Osteoarthritis Synovial Fluid: A Comparison Between Polarized Light and Scanning Electron Microscopy. AB - BACKGROUND: The identification of calcium crystals in synovial fluid (SF) of patients with osteoarthritis (OA) represents an important step in understanding the role of these crystals in synovial inflammation and disease progression. OBJECTIVES: This study aimed to investigate the presence of calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals in SF collected from patients with symptomatic knee OA by scanning electron microscopy (SEM) coupled to x-ray energy dispersive spectroscopy, compensated polarized light microscopy (CPLM), and alizarin red staining. METHODS: Seventy-four patients with knee OA were included in the study. Synovial fluid samples were collected after arthrocentesis and examined under CPLM for the assessment of CPP crystals. Basic calcium phosphate crystals were evaluated by alizarin red staining. All the samples were examined by SEM. The concordance between the 2 techniques was evaluated by Cohen kappa agreement coefficient. RESULTS: Calcium pyrophosphate and BCP crystals were found, respectively, in 23 (31.1%) and 13 (17.5%) of 74 OA SFs by SEM analysis. Calcium pyrophosphate crystals were identified in 23 (31.1%) of 74 samples by CPLM, whereas BCP crystals were suspected in 27 (36.4%) of 74 samples. According to kappa coefficient, the concordance between CPLM and SEM was 0.83 for CPP, and that between alizarin red and SEM was 0.68 for BCP. CONCLUSIONS: The results of our study showed a high level of concordance between the 2 microscope techniques as regards CPP crystal identification and a lower agreement for BCP crystals. Although this finding highlights the difficulty in identifying BCP crystals by alizarin red staining, the use of SEM remains unsuitable to apply in the clinical setting. Because of the in vitro inflammatory effect of BCP crystals, further work on their analysis in SF could provide important information about the OA process. PMID- 27660934 TI - Safety of Corticosteroid Treatment in Rheumatologic Patients With Markers of Hepatitis B Viral Infection: Pilot Evaluation Study. AB - BACKGROUND: Immunosuppressive agents may induce hepatitis B flares. The minimal corticosteroid dose and duration of therapy leading to HBV reactivation is unknown. OBJECTIVE: To assess whether short-term corticosteroid therapy for rheumatologic diseases induces HBV reactivation. METHODS: The records of all HBsAg or HBcore antibodies positive, anti-HBs negative patients who were hospitalized in the rheumatology department during 2001-2014 and treated with corticosteroids were reviewed. Alanine aminotransferase (ALT), HBV serology, and serum HBV DNA at baseline and 1-3 months after discharge were recorded. RESULTS: Complete data were found for 23 patients who were hospitalized 73 times for 7 days of treatment with IV corticosteroids. Eighteen patients were HBsAg positive. The mean methylprednisolone dose was 33.9 +/- 24 mg/d. The concomitant therapy included DMARDs (15), low-dose corticosteroids (8), and biologicals (10). Serum HBV DNA was detected at baseline in seven patients. Three HBsAg-positive patients treated with cyclophosphamide had HBV hepatitis flare-up with elevated ALT. Two HBsAg-positive patients had reappearance of HBV DNA in serum after treatment with azathioprine and infliximab, respectively, but the ALT levels remained normal. Lamivudine therapy reduced the serum HBV DNA and improved ALT levels in all patients. Corticosteroid therapy by itself did not trigger exacerbation of HBV hepatitis. No HBV reactivation occurred in lamivudine-treated patients after recurrent exposure to biologicals or cyclophosphamide. CONCLUSIONS: Short episodes of corticosteroids seem to be safe in HBV carriers, even in the presence of DMARDs, but lamivudine prophylaxis should be considered for patients exposed to biologicals or cyclophosphamide. Larger prospective trials are needed to establish guidelines. PMID- 27660936 TI - The Evelyn Hess Memorial Lecture. PMID- 27660937 TI - Necrotizing Autoimmune Myopathy: A Unique Subset of Idiopathic Inflammatory Myopathy. AB - Necrotizing autoimmune myopathy (NAM) is a recently recognized entity within the spectrum of idiopathic inflammatory myopathies. Diagnosis critically rests on histopathologic demonstration of macrophage predominant myocyte destruction, with few to no lymphocytes. We report our experience with identifying and treating this subset of inflammatory myositis, highlighting the importance of muscle biopsy in diagnosis, association with statin use and malignancy, and challenges of therapy.We present 3 cases that presented to 2 hospitals within our academic system in calendar year 2014 with acute/subacute onset of profound proximal muscle weakness and markedly elevated creatine kinase levels. All patients had been exposed to statins for varying periods. While each electromyogram (EMG) study showed changes with a diffuse inflammatory myopathy, it was not until muscle biopsy was performed when histopathologic features consistent with NAM solidified the diagnosis in all 3 cases. While high-dose glucocorticoids helped provide some degree of improvement in symptoms, none of our cases returned to their preillness baseline independent functioning. Additional immunosuppressive therapy was considered in each case but limited because of comorbidities.These cases demonstrate the importance of pursuing muscle biopsy in all patients with proximal muscle weakness and markedly elevated creatine kinase levels. While symptoms appear consistent with polymyositis, only through muscle biopsy can the diagnosis of NAM be made. Statins have been implicated in NAM, acting through an antibody-dependent mechanism. Combination immunosuppressive therapy has been advocated, but our patient's comorbidities precluded safe use of medications beyond glucocorticoids. PMID- 27660938 TI - A Novel Approach in the Treatment of Calcinosis Cutis. PMID- 27660939 TI - Addison Disease and Discoid Lupus Erythematosus: A Rare Association of Polyglandular Autoimmune Syndrome Type II. PMID- 27660940 TI - Gonagra Puzzle. PMID- 27660941 TI - Coronary and Aortic Involvement as Initial Manifestations of Possible Giant Cell Arteritis in a Patient Without Cardiovascular Comorbidities. PMID- 27660942 TI - Universalis Calcinosis in Adult Dermatomyositis: An "Anti-NXP2 Syndrome". PMID- 27660943 TI - A Subtle Presentation of Fabry Disease. PMID- 27660944 TI - The Responsibilites of Daily Life May Interfere With Adherence to Medications in Patients With Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc). PMID- 27660945 TI - Extensive Pyoderma Gangrenosum Associated With Granulomatosis With Polyangiitis With Both Responsive to Rituximab. PMID- 27660946 TI - Iatrogenic Thenar Eminence Atrophy After Botox A Injection for Secondary Raynaud Phenomenon. PMID- 27660947 TI - Delaying tactics. AB - News that the Government is likely to postpone changes to community care provision surely raises some fundamental questions about the intent and wisdom of the initiative. The rhetoric which accompanied 'Caring for people' ( 1 ) about patient choice and client- centred care has vanished. PMID- 27660948 TI - Mixed reactions over Government stalling. AB - The Government is expected to put the brakes on its community care reforms this week in order to limit next year's poll tax bills. PMID- 27660949 TI - Delighted response to White Paper retreat. AB - The Government has retreated from introducing its NHS White Paper nurse education reforms, a delighted Tony Smith, English National Board chief executive, claimed last week. PMID- 27660951 TI - Welsh nurse education on course for 1992. AB - The Government last week gave in to pressure from the nursing profession and agreed to bring forward the Project 2000 timetable in Wales by one year. PMID- 27660950 TI - Care planned for the homeless mentally ill. AB - Nurses have welcomed the Government's L5 million scheme, unveiled last week, to offer care and accommodation to men- tally-ill people living on the streets in Central London. PMID- 27660954 TI - Extra HV posts spell Victory' in Greenwich. AB - Health visitors are claiming a 'tremendous victory' after managers in Greenwich agreed to increase staffing levels in , line with their proposals last week. PMID- 27660953 TI - Health visiting. AB - Health visit: in recognition of National Health Visitor Week, health minister Virginia Bottomley visited HVA headquarters and met General Secretary Catherine Burns (left), babies, parents and I professionals. The week's activity focused on health promotion. PMID- 27660955 TI - Vital primary health care services in jeopardy. AB - Primary health care services are under serious threat from the National Health Service reforms and will be further jeopardised by delays in implementing the Community Care Act, Royal College of Nursing General Secretary Christine Hancock said last week. PMID- 27660956 TI - One in six DHAs not meeting targets. AB - One in six district health authorities is failing to meet the Government's targets for processing cervical smear tests, Shadow Health Minister Harriet Harman revealed last week. PMID- 27660957 TI - Clinical grading. AB - Glasgow nursing sisters are hoping that the current round of interviews by independent assessors will end a long-running dispute over clinical grading in the city's Mental Health Unit. PMID- 27660959 TI - Ethnic minorities may lose out from reforms. AB - Health professionals must act now to prevent ethnic minority health care losing out in the NHS reforms, a district's health and race conference heard last week. PMID- 27660960 TI - Parliament. AB - Consultations are to begin soon between professional nursing organisations and the Government on increased patient access to health records. PMID- 27660962 TI - World news. AB - United States registered nurses in America have been given a professional boost by two recent developments. PMID- 27660963 TI - ? AB - Africa The AIDS epidemic is spreading rapidly southwards through Africa, according to a report in the New Scientist. PMID- 27660966 TI - Small cell lung cancer research breakthrough. AB - A breakthrough in the treatment of small cell lung cancer has been announced by the Imperial Cancer Research Fund (ICRF). ICRF scientists believe they have found a new and more effective way of preventing the tumour cells from growing, which could revolutionise treatment of the disease. PMID- 27660965 TI - First HIV death was earlier than predicted. AB - Traces of HIV infection have been found in tissue samples from a patient who died in a Manchester hospital more than thirty years ago. PMID- 27660968 TI - Epidural during labour can cause backache. AB - The administration of epidural anaesthetic during labour leads to long-term or chronic backache in eight per cent of women, according to a new study carried out at the Birmingham Maternity Hospital. PMID- 27660967 TI - Goggles may bring relief for migraine sufferers. AB - Flashing goggles which pulse coloured lights into the patient's eyes may bring relief to migraine sufferers, a pilot study at London's Hammersmith Hospital has shown. PMID- 27660970 TI - HIV virulence research gives hope of control. AB - It may be possible to develop new therapies to keep people infected with HIV healthier for longer. PMID- 27660969 TI - Loop diathermy for abnormal smears. AB - Excision of the cervical transformation zone using loop diathermy is an effective treatment for women with abnormal cervical smears. PMID- 27660971 TI - Elderly competence and anaesthesia. AB - Cognitive and functional competence in the elderly is not detectably impaired following either regional or general anaesthesia, researchers say. PMID- 27660973 TI - Paracetamol antidote effective given late. AB - Acetylcystine should be considered in patients who present more than 15 hours after paracetamol overdose. PMID- 27660972 TI - Screening for early endometrial cancer. AB - Vaginosonography may be a suitable screening procedure for diagnosis of endometrial cancer, German researchers say. PMID- 27660974 TI - Creating a better futureAs the RCN/Nursing Standard 'Caring for Romania Appeal' tops L20,000, one member of the appeal team, Colin Beacock describes our unique 'centre of excellence' in Bucharest. AB - To visit Romania is to expose oneself to a : state of constant contradiction in terms. PMID- 27660975 TI - Thanks for the tribute. AB - On Wednesday June 27 I was honoured to be one of a party of members representing the Royal College of Nursing at the Queen Mother's birthday tribute on Horseguards Parade. I know I speak for all the party in thanking the secretaries of the National Boards and the RCN senior officers in all regions for giving us the opportunity to pay tribute to a wonderful lady on behalf of all Royal College of Nursing members. PMID- 27660976 TI - Keeping nurses on their feet. AB - With reference to 'Foot care for patients in hospital' (Nursing StandardJuly 11 17), I found this article informative and easy to read. However, I beg the question, why is there no chiropody service for health care workers? PMID- 27660977 TI - Post-conversion employment fears. AB - I have been an enrolled nurse for 16 years and practised as a district enrolled nurse for 11 years. Last week I was given the opportunity of a placement on a one year conversion course to become a first level nurse. However, I declined this offer when it became apparent that I would have to give up my job, which I thoroughly enjoy, to become a student again in a hospital environment. PMID- 27660978 TI - Rehabilitation and recovery. AB - I would like to respond to the points in Avril Slade's letter (Nursing Standard May 30-June 5). PMID- 27660979 TI - When is a nurse not a nurse? AB - Having been a staff nurse for nearly four years, currently working in a busy A&E department and with a variety of experience and courses under my belt, I thought that I had all the answers to those searching questions that patients like to ask. Even when slightly unsure, I could still have vague answers in the knowledge that my authorita'tive uniform would hide any uncertainty. But then, quite unexpectedly, I too became 'one of them'; I became a patient. PMID- 27660981 TI - Computers Wills A and Stewart T Computers Oxford UP 134pp L6.95 0-19-261754-0. AB - The target audience for Computers is the doctor in general practice; nurses and health visitors are given only a casual reference in the text. The book gives an unbiased view of the potential use of microcomputers in general practice and suggests ways in which they may be introduced into a surgery. PMID- 27660980 TI - Practice nurse handbook Bolden K and Takle B Practice nurse handbook , 2nd edition Blackwell SP 202pp L12.95 0-632-02522-0. AB - The Practice Nurse Handbook updates developments which have occurred since the first edition. Practice nursing is going through a dynamic phase, difficult to keep up with, and since this publication, further developments occurred with the implementation of the new GP contract. PMID- 27660982 TI - Child Health Macfarlane A Child Health et al Oxford Medical 58pp L4.50 0-19 261768-0. AB - A proposal for a national health surveillance programme to be carried out in England and Wales, and possibly Scotland, was recommended by a joint working party with representatives from the HVA, RCN, RCGP, British Paediatric Association and the General Medical Services Committee of the BMA (Hall, D Health for All Children. Oxford UP, 1989). PMID- 27660983 TI - Community charged. AB - Observers of the recent passing of the National Health Service Act could be forgiven for thinking the Community Care element had been dropped or lost in the parliamentary battle. PMID- 27660984 TI - Subordination land autonomy. AB - The story so far_Your intrepid reporter has dragged his sore foot seven blocks from the subway station in downtown Evanston to a rather anonymous-looking office building which almost has a view of the lake. PMID- 27660985 TI - Defending your territory. AB - Paranoia is once again striking sections of the nursing profession. We are seeing defensive territoriality dividing the profession in the face of the most recent onslaught - the GP contract ( 1 ) which took effect on April 1 this year. This reaction is hardly surprising given the way changes have been handled. When fundamental changes are proposed and implemented with little or no room for negotiation, piloting, experimentation or refinement, then what can we expect but a backlash of opposition in the face of such an apparently immovable force? PMID- 27660986 TI - Community stoma care. AB - Successfully rehabilitating a stoma patient in the community means continuing the care provided in the hospital and preparing the patient for a new phase of life. PMID- 27660987 TI - Life cycle assessment of microalgae-based aviation fuel: Influence of lipid content with specific productivity and nitrogen nutrient effects. AB - The aim of this work is to compare the life cycle assessments of low-N and normal culture conditions for a balance between the lipid content and specific productivity. In order to achieve the potential contribution of lipid content to the life cycle assessment, this study established relationships between lipid content (nitrogen effect) and specific productivity based on three microalgae strains including Chlorella, Isochrysis and Nannochloropsis. For microalgae-based aviation fuel, the effects of the lipid content on fossil fuel consumption and greenhouse gas (GHG) emissions are similar. The fossil fuel consumption (0.32 0.68MJ.MJ-1MBAF) and GHG emissions (17.23-51.04gCO2e.MJ-1MBAF) increase (59.70 192.22%) with the increased lipid content. The total energy input decreases (2.13 3.08MJ.MJ-1MBAF, 14.91-27.95%) with the increased lipid content. The LCA indicators increased (0-47.10%) with the decreased nitrogen recovery efficiency (75-50%). PMID- 27660988 TI - Continuous anaerobic co-digestion of Ulva biomass and cheese whey at varying substrate mixing ratios: Different responses in two reactors with different operating regimes. AB - The feasibility of co-digestion of Ulva with whey was investigated at varying substrate mixing ratios in two continuous reactors run with increasing and decreasing proportions of Ulva, respectively. Co-digestion with whey proved beneficial to the biomethanation of Ulva, with the methane yield being greater by up to 1.6-fold in co-digestion phases than in the Ulva mono-digestion phases. The experimental reactors responded differently, in terms of process performance and community structure, to the changes in the substrate mixing ratio. This can be attributed to the different operating regimes between two reactors, which may have caused the microbial communities to develop in different ways to acclimate. Methanosaeta-related populations were the predominant methanogens responsible for the production of methane regardless of different substrate mixing ratios in both reactors. Considering the methane recovery and the Ulva treatment capacity, the optimal fraction of Ulva in the substrate mixture is suggested to be 50-75%. PMID- 27660990 TI - Oxidative degradation of biorefinery lignin obtained after pretreatment of forest residues of Douglas Fir. AB - Harvested forest residues are usually considered a fire hazards and used as "hog fuel" which results in air pollution. In this study, the biorefinery lignin stream obtained after wet explosion pretreatment and enzymatic hydrolysis of forestry residues of Douglas Fir (FS-10) was characterized and further wet oxidized under alkaline conditions. The studies indicated that at 10% solids, 11.7wt% alkali and 15min residence time, maximum yields were obtained for glucose (12.9wt%), vanillin (0.4wt%) at 230 degrees C; formic acid (11.6wt%) at 250 degrees C; acetic acid (10.7wt%), hydroxybenzaldehyde (0.2wt%), syringaldehyde (0.13wt%) at 280 degrees C; and lactic acid (12.4wt%) at 300 degrees C. FTIR analysis of the solid residue after wet oxidation showed that the aromatic skeletal vibrations relating to lignin compounds increased with temperature indicating that higher severity could result in increased lignin oxidation products. The results obtained, as part of the study, is significant for understanding and optimizing processes for producing high-value bioproducts from forestry residues. PMID- 27660989 TI - Nitrogen and phosphorus removal coupled with carbohydrate production by five microalgae cultures cultivated in biogas slurry. AB - In this study, five microalgae strains were cultured for their ability to survive in biogas slurry, remove nitrogen resources and accumulate carbohydrates. It was proved that five microalgae strains adapted in biogas slurry well without ammonia inhibition. Among them, Chlorella vulgaris ESP-6 showed the best performance on carbohydrate accumulation, giving the highest carbohydrate content of 61.5% in biogas slurry and the highest ammonia removal efficiency and rate of 96.3% and 91.7mg/L/d respectively in biogas slurry with phosphorus and magnesium added. Additionally, the absence of phosphorus and magnesium that can be adverse for biomass accumulation resulted in earlier timing of carbohydrate accumulation and magnesium was firstly recognized and proved as the influence factor for carbohydrate accumulation. Microalgae that cultured in biogas slurry accumulated more carbohydrate in cell, making biogas slurry more suitable medium for the improvement of carbohydrate content, thus can be regarded as a new strategy to accumulate carbohydrate. PMID- 27660991 TI - Enhancement of docosahexaenoic acid production by low-energy ion implantation coupled with screening method based on Sudan black B staining in Schizochytrium sp. AB - Schizochytrium sp. is a hopeful docosahexaenoic acid (DHA) producing candidate due to its rapid growth rate and high DHA proportion in total lipid content. In this study, low-energy ion implantation was applied to Schizochytrium sp. to induce high DHA-producing mutants. Screening these mutants by Sudan black B staining, a mutant strain S1 which showed a 61% improvement in DHA production than that of the parent strain was successfully selected. Subsequently, parameters of DHA production of mutant strain S1 were optimized in a 500-mL Erlenmeyer flask. Under the optimum fermentation conditions, the production of DHA and the percentage of DHA in total lipid of mutant strain S1 were 6.52g/L and 46.2%, respectively. This study provides an effective breeding strategy for improved DHA production of Schizochytrium sp. through combination of the novel mutagenesis technology, the effective screening method and fermentation optimization. PMID- 27660992 TI - Enhanced butanol production by solvent tolerance Clostridium acetobutylicum SE25 from cassava flour in a fibrous bed bioreactor. AB - To enhance the butanol productivity and reduce the material cost, acetone, butanol, and ethanol fermentation by Clostridium acetobutylicum SE25 was investigated using batch, repeated-batch and continuous cultures in a fibrous bed bioreactor, where cassava flour was used as the substrate. With periodical nutrient supplementation, stable butanol production was maintained for about 360h in a 6-cycle repeated-batch fermentation with an average butanol productivity of 0.28g/L/h and butanol yield of 0.32g/g-starch. In addition, the highest butanol productivity of 0.63g/L/h and butanol yield of 0.36g/g-starch were achieved when the dilution rate were investigated in continuous production of acetone, butanol, and ethanol using a fibrous bed bioreactor, which were 231.6% and 28.6% higher than those of the free-cell fermentation. On the other hand, this study also successfully comfirmed that the biofilm can provide an effective protection for the microbial cells which are growing in stressful environment. PMID- 27660993 TI - Posttraumatic Stress and Physical Health Functioning: Moderating Effects of Deployment and Postdeployment Social Support in OEF/OIF/OND Veterans. AB - Research indicates that posttraumatic stress disorder (PTSD) is strongly associated with physical health difficulties, and that social support may be protective for both problems. Social support, however, is often broadly conceptualized. The present analysis explores how Veteran-specific social support (during military deployment and postdeployment) may moderate the relationship between PTSD and physical health functioning. Participants were recruited from a VA Medical Center. Self-report data were analyzed from 63 Veterans (17.46% female; 42.86% white) who had been deployed in support of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND). Data indicate that military deployment social support moderated the relationship between PTSD and pain (beta = 0.02, p = 0.02) whereas postdeployment social support moderated the relationship between PTSD and general health perceptions (beta = 0.03, p = 0.01). These findings may be used to better understand the role of support in influencing psychological and physiological processes. PMID- 27660994 TI - The Comparison of Effectiveness of Various Potential Predictors of Response to Treatment With SSRIs in Patients With Depressive Disorder. AB - The substantial non-response rate in depressive patients indicates a continuing need to identify predictors of treatment outcome. The aim of this 6-week, open label study was (1) to compare the efficacy of a priori defined predictors: >=20% reduction in MADRS score at week 1, >=20% reduction in MADRS score at week 2 (RM >= 20% W2), decrease of cordance (RC), and increase of serum and plasma level of brain-derived neurotrophic factor at week 1; and (2) to assess whether their combination yields higher efficacy in the prediction of response to selective serotonin re-uptake inhibitors (SSRIs) than when used singly. Twenty-one patients (55%) achieved a response to SSRIs. The RM >=20% W2 (areas under curve-AUC = 0.83) showed better predictive efficacy compared to all other predictors with the exception of RC. The identified combined model (RM >= 20% W2 + RC), which predicted response with an 84% accuracy (AUC = 0.92), may be a useful tool in the prediction of response to SSRIs. PMID- 27660996 TI - Borderline Personality Disorder and Narcissistic Personality Disorder Diagnoses From the Perspective of the DSM-5 Personality Traits: A Study on Italian Clinical Participants. AB - To evaluate the associations between Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Alternative Model of Personality Disorder traits and domains and categorically diagnosed narcissistic personality disorder (NPD) and borderline personality disorder (BPD), respectively, 238 inpatient and outpatient participants who were consecutively admitted to the Clinical Psychology and Psychotherapy Unit of San Raffaele Hospital in Milan, Italy, were administered the Personality Inventory for DSM-5 (PID-5) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Based on SCID-II, the participants were assigned to the following groups: a) NPD (n = 49), b) BPD (n = 32), c) any other PD (n = 91), and d) no PD (n = 63). Emotional lability, separation insecurity, depressivity, impulsivity, risk taking, and hostility were significantly associated with BPD diagnosis. Attention seeking significantly discriminated participants who received an SCID-II categorical NPD diagnosis. Separation insecurity, impulsivity, distractibility, and perceptual dysregulation were the DSM-5 traits that significantly discriminated BPD participants. Domain-level analyses confirmed and extended trait-level findings. PMID- 27660995 TI - Do Sleep Disturbances Predict or Moderate the Response to Psychotherapy in Bipolar Disorder? AB - This study examined whether sleep disturbance predicted or moderated responses to psychotherapy in participants who participated in STEP-BD, a national, multisite study that examined the effectiveness of different treatment combinations for bipolar disorder. Participants received either a brief psychosocial intervention called collaborative care (CC; n = 130) or intensive psychotherapy (IP; n = 163), with study-based pharmacotherapy. Participants (N = 243) were defined as current (past week) short sleepers (<6 hours/night), normal sleepers (6.5-8.5 hours/night), and long sleepers (>=9 hours/night), according to reported average nightly sleep duration the week before randomization. Sleep disturbances did not predict the likelihood of recovery nor time until recovery from a depressive episode. There was no difference in recovery rates between IP versus CC for normal sleepers, and medium effect sizes were observed for differences in short and long sleepers. In this study, sleep did not play a major role in predicting or moderating response to psychotherapy in bipolar disorder. PMID- 27660997 TI - Are Children or Adolescents More at Risk for Posttraumatic Stress Reactions Following Exposure to Violence?: Evidence From Post-Genocide Rwanda. AB - Whether children or adolescents exhibit higher levels of posttraumatic stress symptoms (PTSS) in response to violence is an unresolved research question. We examine this issue in UNICEF's 1995 National Trauma Survey (NTS) of 8-19-year olds (n = 942) who survived the Rwandan Genocide and lived and attended schools in the community. PTSS were assessed with a symptom checklist based on DSM-IV indexed using an overall score comprising the sum of scores on all items and mean item scores of each of five distinct factors identified in a factor analysis within this sample. Eighty percent of the sample had witnessed massacres; 25%, rape/sexual mutilation. The overall symptom score among children was significantly (p < 0.05) lower than among adolescents. Among the five separate factors, this direct association of age with symptom levels held for two: re experiencing (p < 0.001) and dysphoric arousal (p < 0.05), but not for the remaining three: avoidance, numbing, and anxious arousal. This discordance in factorial response to violence may help explain prevailing inconsistencies in the age-PTSS association reported to date. PMID- 27660998 TI - Theory of Mind in Euthymic Bipolar Patients and First-Degree Relatives. AB - The present study analyzed the capacity for mentalization of patients with bipolar disorder (BD) and their first-degree relatives (FDR) and examined the implications of clinical variables and cognitive deficits. The study recruited 31 patients with type I BD, 18 FDR, and 31 paired healthy controls. Their capacity for mentalization was explored by means of first- and second-order false-belief tasks, the hinting task, and the Movie for the Assessment of Social Cognition (MASC). Patients and FDR were found to have a theory of mind (ToM) deficit when they were evaluated with the MASC, which was also related to a worse neurocognitive performance and to being a patient or FDR. The evidence of ToM deficits in FDRs supports the hypothesis that these deficits could be an independent trait marker for cognitive deficit. Further research is needed on FDR of patients with BD, using sensitive ToM assessment instruments such as the MASC. PMID- 27660999 TI - A Tri-Nucleotide Pattern in a 3' UTR Segment Affects The Activity of a Human Glucocorticoid Receptor Isoform. AB - We previously identified a truncated human glucocorticoid receptor (hGR) isoform of 118 amino acids, hGR-S1(-349A), that despite lacking the major functional domains, was more hyperactive after glucocorticoid treatment than the full-length receptor. Furthermore, its 3' untranslated region (UTR) was required. To dissect the underlying mechanisms for hyperactivity, a series of hGR isoforms with consecutive deletions in the 3' UTR were created to test their transactivation potential using reporter assays. The hGR-S1(-349A) isoform retaining 1303 bp of 3' UTR displayed unusually high activity with or without glucocorticoid stimulation. Unexpectedly, a complete loss of significant activity was observed with isoforms retaining 1293 bp or 1263 bp of 3' UTR. Analysis of the 20 bp region neighboring the 1293 bp site showed a pattern: 3'UTR termination at every third base pair in this region resulted in a loss of transactivation potential while the other sites retained hyperactivity with or without glucocorticoid stimulation. Variations in the activity of an hGR isoform, due to changes in the 3' UTR sequence configuration, may provide an important link in explaining inconsistent responses to glucocorticoid treatment in individuals and ultimately enable tailored, patient-specific care. Furthermore, understanding the mechanisms underlying the cyclic hyperactivity/loss of activity phenomenon may be a step toward identifying a novel mechanism of gene regulation. PMID- 27661000 TI - Alpha7 Nicotine Acetylcholine Receptor Agonist PNU-282987 Attenuates Acute Lung Injury in a Cardiopulmonary Bypass Model in Rats. AB - OBJECTIVE: Cardiopulmonary bypass (CPB) carries a risk of lung ischemia reperfusion, leading to acute lung injury (ALI). Alpha7 nicotinic acetylcholine receptor (alpha7nAChR) has been implicated in the release of high mobility group box1 (HMGB1), which promotes systemic inflammation in response to ischemia reperfusion injury. However, the specific role of alpha7nAChR in CPB is poorly understood. This study employed the alpha7nAChR agonist PNU-282987 and a rat model of CPB to determine whether alpha7nAChR was associated with CPB-induced lung damage. METHODS: Thirty Sprague-Dawley rats were randomly divided into five groups as follows: normal group, sham group, CPB group, PNU-282987 plus CPB group, and PNU-282987 plus sham group. Rats were subjected to CPB under anesthesia for 60 min. PNU-282987 (4.8 mg/kg) was administered via arterial inflow. Two hours post-CPB, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations. RESULTS: In CPB rats, structural damage in the lung was marked. Density of alpha7nAChR of the lung in the CPB group was significantly less than all other groups, while lung edema, inflammatory markers in serum and lung, protein concentrations in BALF were significantly higher. In the PNU-282987 plus CPB group, by all the above measures the CPB-associated effects were significantly ameliorated but were not identical to the control groups. CONCLUSION: Our results suggest that PNU-282987 affords protective effect against CPB-induced ALI, and inhibits HMGB1 release. PMID- 27661002 TI - Evaluating radiocarpal cartilage matrix changes 3-months after anti-TNF treatment for rheumatoid arthritis using MR T1rho imaging. AB - PURPOSE: To evaluate the feasibility of MR T1rho in assessing radiocarpal cartilage matrix changes following rheumatoid arthritis (RA) treatment. MATERIALS AND METHODS: Five healthy controls and nine RA patients were studied: three RA patients with low disease activity that were treated with methotrexate (MTX) alone and six with active disease despite MTX treatment who were additionally treated with certolizumab pegol, an anti-tumor necrosis factor biologic. Wrist 3 Tesla MRI were acquired at baseline and 3-month follow-up. T1rho were quantified for lunar, radius, and scaphoid cartilage. Reproducibility was evaluated using coefficients of variation (CV). Longitudinal changes were evaluated with t-test and relationships between T1rho with clinical, MRI, and patient-reported outcomes were evaluated with Spearman's rho. RESULTS: Scan/re-scan CVs of T1rho values were all <5%, and intra- and inter-reader CVs were all < 2.0%. Baseline scaphoid T1rho values were significantly higher in RA patients compared with healthy controls (P = 0.032). Changes in T1rho (baseline, 3-month) were correlated with EULAR treatment response criteria: -2.26 +/- 0.75 ms, 1.08 +/- 0.52 ms, and 2.18 +/- 0.45 ms for good, moderate, and nonresponders, respectively. Significant correlations were found between changes in global T1rho values and changes in DAS28-CRP (rs = 0.683; P = 0.042), MHQ (rs = -0.783; P = 0.013), and HAQ (rs = 0.833; P = 0.010). CONCLUSION: Despite the limited sample size and follow-up time points, there were significant correlations between changes in radiocarpal T1rho and changes in disease activity as assessed by clinical and patient-reported outcomes. Our findings encourage further research into MR T1rho assessment of RA disease activity and treatment response. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1514-1522. PMID- 27661001 TI - Astrocyte-produced leukemia inhibitory factor expands the neural stem/progenitor pool following perinatal hypoxia-ischemia. AB - Brain injuries, such as cerebral hypoxia-ischemia (H-I), induce a regenerative response from the neural stem/progenitors (NSPs) of the subventricular zone (SVZ); however, the mechanisms that regulate this expansion have not yet been fully elucidated. The Notch- Delta-Serrate-Lag2 (DSL) signaling pathway is considered essential for the maintenance of neural stem cells, but it is not known if it is necessary for the expansion of the NSPs subsequent to perinatal H I injury. Therefore, the aim of this study was to investigate whether this pathway contributes to NSP expansion in the SVZ after H-I and, if so, to establish whether this pathway is directly induced by H-I or regulated by paracrine factors. Here we report that Notch1 receptor induction and one of its ligands, Delta-like 1, precedes NSP expansion after perinatal H-I in P6 rat pups and that this increase occurs specifically in the most medial cell layers of the SVZ where the stem cells reside. Pharmacologically inhibiting Notch signaling in vivo diminished NSP expansion. With an in vitro model of H-I, Notch1 was not induced directly by hypoxia, but was stimulated by soluble factors, specifically leukemia inhibitory factor, produced by astrocytes within the SVZ. These data confirm the importance both of the Notch-DSL signaling pathway in the expansion of NSPs after H-I and in the role of the support cells in their niche. They further support the body of evidence that indicates that leukemia inhibitory factor is a key injury-induced cytokine that is stimulating the regenerative response of the NSPs. (c) 2016 Wiley Periodicals, Inc. PMID- 27661003 TI - Differentiation of pancreatic carcinoma and mass-forming focal pancreatitis: qualitative and quantitative assessment by dynamic contrast-enhanced MRI combined with diffusion-weighted imaging. AB - Differentiation between pancreatic carcinoma (PC) and mass-forming focal pancreatitis (FP) is invariably difficult. For the differential diagnosis, we qualitatively and quantitatively assessed the value of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in PC and FP in the present study. This study included 32 PC and 18 FP patients with histological confirmation who underwent DCE-MRI and DWI. The time-signal intensity curve (TIC) of PC and FP were classified into 5 types according to the time of reaching the peak, namely, type I, II, III, IV, and V, respectively, and two subtypes, namely, subtype-a (washout type) and subtype-b (plateau type) according to the part of the TIC profile after the peak. Moreover, the mean and relative apparent diffusion coefficient (ADC) value between PC and FP on DWI were compared. The type V TIC was only recognized in PC group (P < 0.01). Type IV b were more frequently observed in PC (P = 0.036), while type- IIa (P < 0.01), type- Ia (P = 0.037) in FP. We also found a significant difference in the mean and relative ADC value between PC and FP. The combined image set of DCE-MRI and DWI yielded an excellent sensitivity, specificity, and diagnostic accuracy (96.9%, 94.4%, and 96.0%). The TIC of DCE-MRI and ADC value of DWI for pancreatic mass were found to provide reliable information in differentiating PC from FP, and the combination of DCE-MRI and DWI can achieve a higher sensitivity, specificity, and diagnostic accuracy. PMID- 27661004 TI - Frequent somatic TERT promoter mutations and CTNNB1 mutations in hepatocellular carcinoma. AB - Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma. PMID- 27661007 TI - Strategies for power calculations in predictive biomarker studies in survival data. AB - PURPOSE: Biomarkers and genomic signatures represent potentially predictive tools for precision medicine. Validation of predictive biomarkers in prospective or retrospective studies requires statistical justification of power and sample size. However, the design of these studies is complex and the statistical methods and associated software are limited, especially in survival data. Herein, we address common statistical design issues relevant to these two types of studies and provide guidance and a general template for analysis. METHODS: A statistical interaction effect in the Cox proportional hazards model is used to describe predictive biomarkers. The analytic form by Peterson et al. and Lachin is utilized to calculate the statistical power for both prospective and retrospective studies. RESULTS: We demonstrate that the common mistake of using only Hazard Ratio's Ratio (HRR) or two hazard ratios (HRs) can mislead power calculations. We establish that the appropriate parameter settings for prospective studies require median survival time (MST) in 4 subgroups (treatment and control in positive biomarker, treatment and control in negative biomarker). For the retrospective study which has fixed survival time and censored status, we develop a strategy to harmonize the hypothesized parameters and the study cohort. Moreover, we provide an easily-adapted R software application to generate a template of statistical plan for predictive biomarker validation so investigators can easily incorporate into their study proposals. CONCLUSION: Our study provides guidance and software to help biostatisticians and clinicians design sound clinical studies for testing predictive biomarkers. PMID- 27661005 TI - Systematically characterizing dysfunctional long intergenic non-coding RNAs in multiple brain regions of major psychosis. AB - Schizophrenia (SZ) and bipolar disorder (BD) are severe neuropsychiatric disorders with serious impact on patients, together termed "major psychosis". Recently, long intergenic non-coding RNAs (lincRNAs) were reported to play important roles in mental diseases. However, little was known about their molecular mechanism in pathogenesis of SZ and BD. Here, we performed RNA sequencing on 82 post-mortem brain tissues from three brain regions (orbitofrontal cortex (BA11), anterior cingulate cortex (BA24) and dorsolateral prefrontal cortex (BA9)) of patients with SZ and BD and control subjects, generating over one billion reads. We characterized lincRNA transcriptome in the three brain regions and identified 20 differentially expressed lincRNAs (DELincRNAs) in BA11 for BD, 34 and 1 in BA24 and BA9 for SZ, respectively. Our results showed that these DELincRNAs exhibited brain region-specific patterns. Applying weighted gene co-expression network analysis, we revealed that DELincRNAs together with other genes can function as modules to perform different functions in different brain regions, such as immune system development in BA24 and oligodendrocyte differentiation in BA9. Additionally, we found that DNA methylation alteration could partly explain the dysregulation of lincRNAs, some of which could function as enhancers in the pathogenesis of major psychosis. Together, we performed systematical characterization of dysfunctional lincRNAs in multiple brain regions of major psychosis, which provided a valuable resource to understand their roles in SZ and BD pathology and helped to discover novel biomarkers. PMID- 27661008 TI - Treadmill running exercise prevents senile osteoporosis and upregulates the Wnt signaling pathway in SAMP6 mice. AB - This study examined the effects of different exercise intensities and durations on bone mineral density (BMD) and bone strength in senescence-accelerated mouse prone 6 (SAMP6) and determined the involvement of the Wnt signaling pathway in exercise-induced osteogenesis. Three-month-old male SAMP6 mice were randomly assigned to different speeds of treadmill running exercise representing low, medium and high intensity, with the duration of five and nine weeks, respectively. We showed that medium-intensity exercise had positive effects on skeletal health, including BMD and bone strength, and the efficacy was higher than that of low-intensity exercise. Interestingly, high-intensity exercise can maintain or even increase bone strength, despite its negative effects on bone mass. Nine weeks of exercise was superior to 5 weeks of exercise, particularly for low-intensity exercise. Furthermore, these effects of exercise-induced osteogenesis are accompanied by activation of the Wnt signaling pathway. Taken together, these results suggest that the positive effects of exercise on osteoporosis prevention are intensity and duration-dependent, and may involve the regulation of Wnt signaling pathways. PMID- 27661010 TI - Four birds with one stone? Reparative, neuroplastic, cardiorespiratory, and metabolic benefits of aerobic exercise poststroke. AB - PURPOSE OF REVIEW: Converging evidence from animal models of stroke and clinical trials suggests that aerobic exercise has effects across multiple targets. RECENT FINDINGS: The subacute phase is characterized by a period of heightened neuroplasticity when aerobic exercise has the potential to optimize recovery. In animals, low intensity aerobic exercise shrinks lesion size and reduces cell death and inflammation, beginning 24 h poststroke. Also in animals, aerobic exercise upregulates brain-derived neurotrophic factor near the lesion and improves learning. In terms of neuroplastic effects, clinical trial results are less convincing and have only examined effects in chronic stroke. Stroke patients demonstrate cardiorespiratory fitness levels below the threshold required to carry out daily activities. This may contribute to a 'neurorehabilitation ceiling' that limits capacity to practice at a high enough frequency and intensity to promote recovery. Aerobic exercise when delivered 2-5 days per week at moderate to high intensity beginning as early as 5 days poststroke improves cardiorespiratory fitness, dyslipidemia, and glucose tolerance. SUMMARY: Based on the evidence discussed and applying principles of periodization commonly used to prepare athletes for competition, we have created a model of aerobic training in subacute stroke in which training is delivered in density blocks (duration * intensity) matched to recovery phases. PMID- 27661009 TI - BMP signaling and its paradoxical effects in tumorigenesis and dissemination. AB - Bone morphogenetic proteins (BMPs) play important roles in embryonic and postnatal development by regulating cell differentiation, proliferation, motility, and survival, thus maintaining homeostasis during organ and tissue development. BMPs can lead to tumorigenesis and regulate cancer progression in different stages. Therefore, we summarized studies on BMP expression, the clinical significance of BMP dysfunction in various cancer types, and the molecular regulation of various BMP-related signaling pathways. We emphasized on the paradoxical effects of BMPs on various aspects of carcinogenesis, including epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), and angiogenesis. We also reviewed the molecular mechanisms by which BMPs regulate tumor generation and progression as well as potential therapeutic targets against BMPs that might be valuable in preventing tumor growth and invasion. PMID- 27661011 TI - Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases. AB - Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001).ATD is more associated with rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus and RA, with early referral to rheumatologists for close follow-up and early diagnoses for appropriate disease management of the disease, as early disease control will allow better quality of life. PMID- 27661012 TI - Clinical application of ICF key codes to evaluate patients with dysphagia following stroke. AB - This study was aimed to identify and evaluate the International Classification of Functioning (ICF) key codes for dysphagia in stroke patients. Thirty patients with dysphagia after stroke were enrolled in our study. To evaluate the ICF dysphagia scale, 6 scales were used as comparisons, namely the Barthel Index (BI), Repetitive Saliva Swallowing Test (RSST), Kubota Water Swallowing Test (KWST), Frenchay Dysarthria Assessment, Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). Multiple regression analysis was performed to quantitate the relationship between the ICF scale and the other 7 scales. In addition, 60 ICF scales were analyzed by the least absolute shrinkage and selection operator (LASSO) method. A total of 21 ICF codes were identified, which were closely related with the other scales. These included 13 codes from Body Function, 1 from Body Structure, 3 from Activities and Participation, and 4 from Environmental Factors. A topographic network map with 30 ICF key codes was also generated to visualize their relationships. The number of ICF codes identified is in line with other well-established evaluation methods. The network topographic map generated here could be used as an instruction tool in future evaluations. We also found that attention functions and biting were critical codes of these scales, and could be used as treatment targets. PMID- 27661006 TI - Type I insulin-like growth factor receptor signaling in hematological malignancies. AB - The insulin-like growth factor (IGF) signaling system plays key roles in the establishment and progression of different types of cancer. In agreement with this idea, substantial evidence has shown that the type I IGF receptor (IGF-IR) and its primary ligand IGF-I are important for maintaining the survival of malignant cells of hematopoietic origin. In this review, we discuss current understanding of the role of IGF-IR signaling in cancer with a focus on the hematological neoplasms. We also address the emergence of IGF-IR as a potential therapeutic target for the treatment of different types of cancer including plasma cell myeloma, leukemia, and lymphoma. PMID- 27661013 TI - Alcohol use and alcohol-related problems among adolescents in China: A large scale cross-sectional study. AB - Alcohol misuse among adolescents is a common issue worldwide and is an emerging problem in China. This study aimed to investigate the prevalence of alcohol drinking and alcohol-related problems among Chinese adolescents and to explore their risk factors and connections.A cross-sectional study using an anonymous questionnaire was conducted among junior and senior high school students between 2010 and 2012. Data on self-reported alcohol use, alcohol-related problems, school factors, family factors, and psychosocial factors were collected. Descriptive analyses were made of the proportions of sociodemographics, family, school, and psychosocial factors. Multilevel logistic regression models were conducted to analyze the risk factors for alcohol drinking and alcohol-related problems.Of the 105,752 students who ranged in age from 9 to 21 years, the prevalence of current drinking among students was 7.3%, and 13.2% students reported having alcohol-related problems. Male students were 1.78 (95% confidence interval [CI] = 1.69-1.87) times more likely to be involved in current drinking and 1.86 (95% CI = 1.79-1.93) times more likely to have alcohol-related problems. Higher grade level students were at a higher risk of current drinking (adjusted odds ratio [AOR] = 1.09, 95% CI = 1.05-1.13) and having alcohol-related problems (AOR = 1.43, 95% CI = 1.42-1.58). Older students were more likely to report current drinking (AOR = 1.06, 95% CI = 1.04-1.17) and having alcohol-related problems (AOR = 1.83, 95% CI = 1.82-1.85). Having poor classmate relations (AOR = 1.28, 95% CI = 1.03-1.37), having poor relationships with teachers (AOR = 1.08, 95% CI = 1.00-1.16), and below average academic achievement (AOR = 1.50, 95% CI = 1.41-1.59) were positively associated with current drinking. Moreover, students with suicidal ideation were at a higher risk of current drinking (AOR = 1.70, 95% CI = 1.61-1.81) and having alcohol-related problems (AOR = 2.08, 95% CI = 1.98 2.16). Having higher Center for Epidemiology Scale for Depression scores was positively associated with current drinking (AOR = 1.09, 95% CI = 1.05-1.11) and having alcohol-related problems (AOR = 1.08, 95% CI = 1.06-1.18).Alcohol drinking and alcohol-related problems among Chinese adolescents are major public health problems, and effective preventive programs will require full consideration of the individual, social, and environmental factors that facilitate and prevent alcohol use. PMID- 27661014 TI - Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22. AB - Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure >=140 mmHg and/or diastolic blood pressure >=90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension. PMID- 27661016 TI - Facet joint disturbance induced by miniscrews in plated cervical laminoplasty: Dose it influence the clinical and radiologic outcomes? AB - A retrospective cohort study. Plated cervical laminoplasty is an increasingly common technique. A unique facet joint disturbance induced by lateral mass miniscrews penetrating articular surface was noticed. Facet joints are important to maintain cervical spine stability and kinetic balance. Whether this facet joint disturbance could affect clinical and radiologic results is still unknown. The objective of this study is to investigate the clinical and radiologic outcomes of patients with facet joints disturbance induced by miniscrews in plated cervical laminoplasty.A total of 105 patients who underwent cervical laminoplasty with miniplate fixation between May 2010 and February 2014 were comprised. Postoperative CT images were used to identify whether facet joints destroyed by miniscrews. According to facet joints destroyed number, all the patients were divided into: group A (none facet joint destroyed), group B (1-2 facet joints destroyed), and group C (>=3 facet joints destroyed). Clinical data (JOA, VAS, and NDI scores), radiologic data (anteroposterior diameter and Palov ratio), and complications (axial symptoms and C5 palsy) were evaluated and compared among the groups.There were 38, 40, and 27 patients in group A, B, and C, respectively. The overall facet joints destroyed rate was 30.7%. All groups gained significant JOA and NDI scores improvement postoperatively. The preoperative JOA, VAS, NDI scores, and postoperative JOA scores did not differ significantly among the groups. The group C recorded significant higher postoperative VAS scores than group A (P = 0.002) and B (P = 0.014) and had significant higher postoperative NDI scores than group A (P = 0.002). The pre- and postoperative radiologic data were not significant different among the groups. The group C had a significant higher axial symptoms incidence than group A (12/27 vs 8/38, P = 0.041).Facet joints disturbance caused by miniscrews in plated cervical laminoplasty may not influence neurological recovery and spinal canal expansion, but may negatively affect postoperative axial symptoms. PMID- 27661017 TI - Recovery of an injured cingulum via an aberrant neural tract in a patient with traumatic brain injury: A case report. AB - BACKGROUND: We report on a patient who appeared to show recovery of an injured anterior cingulum via an aberrant neural tract between an injured cingulum and the basalis nucleus of Meynert following traumatic brain injury (TBI), which was demonstrated on diffusion tensor tractography (DTT). METHODS: A 47-year-old male who had suffered a pedestrian traffic accident underwent conservative management for diffuse traumatic axonal injury. When starting rehabilitation at 6 weeks after onset, evaluation using the Mini-Mental State Examination (MMSE) could not be performed due to the severity of his cognitive dysfunction. The patient showed improvement of cognitive dysfunction on MMSE with 10 at 2 months, 13 at 6 months, and 26 at 10 months after onset. RESULTS: On 6-week DTT, discontinuation superior to the genu of the corpus callosum was observed in both cingulums. However, on 6 month DTT, the discontinued anterior part of the right cingulum was elongated anteriorly, not through the cingulum, but through the anterolateral subcortical white matter of the cingulum, while on 10-month DTT, this elongated neural tract of the right cingulum was connected to the right basalis nucleus of Meynert in the basal forebrain. CONCLUSION: Recovery of an injured anterior cingulum via an aberrant neural tract between an injured cingulum and Ch 4 was demonstrated in a patient with TBI. Our result appears to suggest a mechanism for recovery of an injured cingulum following brain injury. PMID- 27661015 TI - Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients. AB - We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 >=1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value >=1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool. PMID- 27661018 TI - Impact of social and clinical factors on diagnostic delay of breast cancer: A Cross-sectional Study. AB - One of the reasons for high mortality of breast cancer is long delay in seeking medical care. This study was designed to measure the association of a wide range of socio-demographic and clinical factors with the diagnostic delay in breast cancer among Iranian patients.This study was conducted on 505 newly diagnosed patients with breast cancer from southern part of Iran. Medical files of the patients who were admitted to the hospital from November 2013 to May 2015 were examined and clinical and demographic information were extracted.According to the results, illiterate patients were diagnosed on average 87.42 days later compared with those with a college degree (95%CI: 29.68-145.16, P = 0.003) and those from rural area were diagnosed on average 72.48 days later (95%CI: 35.94-109.03, P = 0.001) compared with urban residences. Single women were diagnosed 65.99 days later (95%CI: 7.37-124.61, P = 0.02) compared with those married. Lobular or medullary types of cancer were diagnosed 65.19 days later (95%CI: 2.67-127.70, P = 0.04) compared with ductal type. On the other hand, those who were able to perform breast self-exam were diagnosed 49.07 days earlier compared with others (95%CI: 18.69-79.45, P = 0.002). Those felt lump as the initiating symptom were diagnosed 62.01 days earlier, (95%CI: 8.17-115.85, P = 0.02) compared with those with other initial symptoms. The only factor associated with doctors diagnosis delay was the place of residence as rural residences were diagnosed on average 87.42 days later compared with urban residences, (95%CI: 53.82-121.92, P = 0.001).Higher education, living in cities, ductal type of tumor, and noticing lump in breast were the most important demographic and clinical factors associated with shorter breast cancer diagnosis delay. Informing women and doctors, especially general physicians who are practicing in rural areas, of the common symptoms of breast cancer as well as training women to perform breast self examination are effective measures in reducing breast cancer diagnosis delay. Providing accessible and effective diagnosis services to rural women reduces diagnosis delay in rural patients. PMID- 27661019 TI - Gastrointestinal stromal tumors (GISTs) and second malignancies: A novel "sentinel tumor"? A monoinstitutional, STROBE-compliant observational analysis. AB - Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis.A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-alpha genes was performed in all patients. Following the involvement of KRAS mutation in many tumors' pathogenesis, analysis of KRAS was performed in patients with also second neoplasms.Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-alpha mutation (n. 2) and exon 18 PDGFR-alpha mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months.The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. PMID- 27661020 TI - The effectiveness of complementary manual therapies for pregnancy-related back and pelvic pain: A systematic review with meta-analysis. AB - BACKGROUND: Low back pain and pelvic girth pain are common in pregnancy and women commonly utilize complementary manual therapies such as massage, spinal manipulation, chiropractic, and osteopathy to manage their symptoms. OBJECTIVE: The aim of this systematically review was to critically appraise and synthesize the best available evidence regarding the effectiveness of manual therapies for managing pregnancy-related low back and pelvic pain. METHODS: Seven databases were searched from their inception until April 2015 for randomized controlled trials. Studies investigating the effectiveness of massage and chiropractic and osteopathic therapies were included. The study population was pregnant women of any age and at any time during the antenatal period. Study selection, data extraction, and assessment of risk of bias were conducted by 2 reviewers independently, using the Cochrane tool. Separate meta-analyses were conducted to compare manual therapies to different control interventions. RESULTS: Out of 348 nonduplicate records, 11 articles reporting on 10 studies on a total of 1198 pregnant women were included in this meta-analysis. The therapeutic interventions predominantly involved massage and osteopathic manipulative therapy. Meta analyses found positive effects for manual therapy on pain intensity when compared to usual care and relaxation but not when compared to sham interventions. Acceptability did not differ between manual therapy and usual care or sham interventions. CONCLUSIONS: There is currently limited evidence to support the use of complementary manual therapies as an option for managing low back and pelvic pain during pregnancy. Considering the lack of effect compared to sham interventions, further high-quality research is needed to determine causal effects, the influence of the therapist on the perceived effectiveness of treatments, and adequate dose-response of complementary manual therapies on low back and pelvic pain outcomes during pregnancy. PMID- 27661021 TI - Efficacy and safety of noninvasive ventilation in patients after cardiothoracic surgery: A PRISMA-compliant systematic review and meta-analysis. AB - BACKGROUND: Noninvasive ventilation (NIV) is a promising therapeutic strategy after cardiothoracic surgery. This study aimed to meta-analyze the efficacy and safety of NIV as compared to conventional management after cardiothoracic surgery. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing NIV with conventional management after cardiothoracic surgery. Relative risk (RR), standard mean difference (SMD), and 95% confidence intervals (CIs) were used to measure the efficacy and safety of NIV using random-effects model. Heterogeneity was evaluated using the Q statistic. RESULTS: This study included 14 RCTs (1740 patients) for the evaluation of efficacy and safety of NIV as compared to conventional management after cardiothoracic surgery. Overall, NIV had minimal effect on the risk of mortality (RR: 0.64; 95% CI: 0.36-1.14; P = 0.127), endotracheal intubation (RR: 0.52; 95% CI: 0.24-1.11; P = 0.090), respiratory (RR: 0.70; 95% CI: 0.47-1.30; P = 0.340), cardiovascular (RR: 0.81; 95% CI: 0.54 1.22; P = 0.306), renal (RR: 0.70; 95% CI: 0.26-1.92; P = 0.491), and other complications (RR: 0.72; 95% CI: 0.38-1.36; P = 0.305), respiratory rate (SMD: 0.10; 95% CI: -1.21-1.01; P = 0.862), heart rate (SMD: -0.27; 95% CI: -0.76-0.22; P = 0.288), PaO2/FiO2 ratio (SMD: 0.34; 95% CI: -0.17-0.85; P = 0.194), PaCO2 (SMD: 0.83; 95% CI: -0.12-1.77; P = 0.087), systolic pressure (SMD: -0.04; 95% CI: -0.25-0.17; P = 0.700), pH (SMD: -0.01; 95% CI: -0.44-0.43; P = 0.974), length of ICU stay (SMD: -0.19; 95% CI: -0.47-0.08; P = 0.171), and hospital stay (SMD: -0.31; 95% CI: -1.00-0.38; P = 0.373). Sensitivity analysis showed that NIV was associated with higher levels of PaO2/FiO2 ratio (SMD: 0.52; 95% CI: 0.00 1.05; P = 0.048) and lower risk of endotracheal intubation (RR: 0.38; 95% CI: 0.22-0.66; P = 0.001). CONCLUSION: As compared to conventional management, the use of NIV after cardiothoracic surgery improved patient's oxygenation and decreased the need for endotracheal intubation, without significant complications. PMID- 27661023 TI - Randomized clinical trial comparing abluminal biodegradable polymer sirolimus eluting stents with durable polymer sirolimus-eluting stents: Nine months angiographic and 5-year clinical outcomes. AB - BACKGROUND: The biodegradable polymer drug-eluting stents (DES) were developed to improve vascular healing. However, further data and longer-term follow-up are needed to confirm safety and efficacy of these stents. This randomized clinical trial aimed to compare safety and efficacy of 2 sirolimus-eluting stents (SES): Cordimax-a novel abluminal biodegradable polymer SES and Cypher Select-a durable polymer SES, at 9 months angiographic and 5-year clinical follow-up. METHODS: We randomized 402 patients with coronary artery disease to percutaneous coronary intervention with Cordimax (n = 202) or Cypher select (n = 200). Angiographic follow-up was performed at 9 months after the index procedure and clinical follow up annually up to 5 years. The primary endpoint was angiographic in-stent late luminal loss (LLL). Secondary endpoints included angiographic restenosis rate, target vessel revascularization (TVR), and major adverse cardiac events (MACEs; defined as cardiac death, myocardial infarction, or TVR) at 5-year follow-up. RESULTS: Cordimax was noninferior to Cypher select for in-stent LLL (0.25 +/- 0.47 vs 0.18 +/- 0.49 mm; P = 0.587) and in-stent mean diameter stenosis (22.19 +/- 12.21% vs 19.89 +/- 10.79%; P = 0.064) at 9 months angiographic follow-up. The MACE rates were not different at 1 year (5.9% vs 4.0%, P = 0.376); however, MACE rates from 2 to 5 years were lower in the Cordimax group (6.8% vs 13.1%; P = 0.039). CONCLUSION: Abluminal biodegradable polymer SES is noninferior to durable polymer SES at 9-month angiographic and 1-year clinical follow-up. However, MACE rates from 2 to 5 years were less in the abluminal biodegradable polymer group. PMID- 27661022 TI - The effectiveness of dry-cupping in preventing post-operative nausea and vomiting by P6 acupoint stimulation: A randomized controlled trial. AB - BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after general anesthesia, and the prevalence ranges between 25% and 30%. The aim of this study was to determine the preventive effects of dry cupping on PONV by stimulating point P6 in the wrist. METHODS: This was a randomized controlled trial conducted at the Imam Reza Hospital in Kermanshah, Iran. The final study sample included 206 patients (107 experimental and 99 controls). Inclusion criteria included the following: female sex; age>18 years; ASA Class I-II; type of surgery: laparoscopic cholecystectomy; type of anesthesia: general anesthesia. Exclusion criteria included: change in the type of surgery, that is, from laparoscopic cholecystectomy to laparotomy, and ASA-classification III or more. Interventions are as follows: pre surgery, before the induction of anesthesia, the experimental group received dry cupping on point P6 of the dominant hand's wrist with activation of intermittent negative pressure. The sham group received cupping without activation of negative pressure at the same point. Main outcome was that the visual analogue scale was used to measure the severity of PONV. RESULTS: The experimental group who received dry cupping had significantly lower levels of PONV severity after surgery (P < 0.001) than the control group. The differences in measure were maintained after controlling for age and ASA in regression models (P < 0.01). CONCLUSION: Traditional dry cupping delivered in an operation room setting prevented PONV in laparoscopic cholecystectomy patients. PMID- 27661024 TI - A retrospective study to validate an intraoperative robotic classification system for assessing the accuracy of kirschner wire (K-wire) placements with postoperative computed tomography classification system for assessing the accuracy of pedicle screw placements. AB - This purpose of this retrospective study is validation of an intraoperative robotic grading classification system for assessing the accuracy of Kirschner wire (K-wire) placements with the postoperative computed tomography (CT)-base classification system for assessing the accuracy of pedicle screw placements.We conducted a retrospective review of prospectively collected data from 35 consecutive patients who underwent 176 robotic assisted pedicle screws instrumentation at Kaohsiung Medical University Hospital from September 2014 to November 2015. During the operation, we used a robotic grading classification system for verifying the intraoperative accuracy of K-wire placements. Three months after surgery, we used the common CT-base classification system to assess the postoperative accuracy of pedicle screw placements. The distributions of accuracy between the intraoperative robot-assisted and various postoperative CT based classification systems were compared using kappa statistics of agreement.The intraoperative accuracies of K-wire placements before and after repositioning were classified as excellent (131/176, 74.4% and 133/176, 75.6%, respectively), satisfactory (36/176, 20.5% and 41/176, 23.3%, respectively), and malpositioned (9/176, 5.1% and 2/176, 1.1%, respectively)In postoperative CT-base classification systems were evaluated. No screw placements were evaluated as unacceptable under any of these systems. Kappa statistics revealed no significant differences between the proposed system and the aforementioned classification systems (P <0.001).Our results revealed no significant differences between the intraoperative robotic grading system and various postoperative CT-based grading systems. The robotic grading classification system is a feasible method for evaluating the accuracy of K-wire placements. Using the intraoperative robot grading system to classify the accuracy of K-wire placements enables predicting the postoperative accuracy of pedicle screw placements. PMID- 27661025 TI - Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography. AB - Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 +/- 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 +/- 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate <30 mL/min.AKI developed in 22/249 (8.8%) and in 6/203 (3%) of the CECT and the Control groups, respectively (P = 0.01). The multivariate logistic regression analysis showed that AKI was significantly associated with contrast medium administration (odds ratio [OR]: 3.242, 95% confidence interval [CI]: 1.255-8.375; P = 0.015), female sex (OR: 0.339, 95% CI: 0.139-0.827; P = 0.017), and sCr values (OR: 0.124, 95% CI: 0.016 0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109-7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073-0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001-1.037; P = 0.043) correlated with CI AKI development at multivariate analysis.CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors. PMID- 27661026 TI - Vertebral body or intervertebral disc wedging: which contributes more to thoracolumbar kyphosis in ankylosing spondylitis patients?: A retrospective study. AB - Both vertebral body wedging and disc wedging are found in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. However, their relative contribution to thoracolumbar kyphosis is not fully understood. The objective of this study was to compare different contributions of vertebral and disc wedging to the thoracolumbar kyphosis in AS patients, and to analyze the relationship between the apical vertebral wedging angle and thoracolumbar kyphosis.From October 2009 to October 2013, a total of 59 consecutive AS patients with thoracolumbar kyphosis with a mean age of 38.1 years were recruited in this study. Based on global kyphosis (GK), 26 patients with GK < 70 degrees were assigned to group A, and the other 33 patients with GK >= 70 degrees were included in group B. Each GK was divided into disc wedge angles and vertebral wedge angles. The wedging angle of each disc and vertebra comprising the thoracolumbar kyphosis was measured, and the proportion of the wedging angle to the GK was calculated accordingly. Intergroup and intragroup comparisons were subsequently performed to investigate the different contributions of disc and vertebra to the GK. The correlation between the apical vertebral wedging angle and GK was calculated by Pearson correlation analysis. The duration of disease and sex were also recorded in this study.With respect to the mean disease duration, significant difference was observed between the two groups (P < 0.01). The wedging angle and wedging percentage of discs were significantly higher than those of vertebrae in group A (34.8 degrees +/- 2.5 degrees vs 26.7 degrees +/- 2.7 degrees , P < 0.01 and 56.6% vs 43.4%, P < 0.01), whereas disc wedging and disc wedging percentage were significantly lower than vertebrae in group B (37.6 degrees +/- 7.0 degrees vs 50.1 degrees +/- 5.1 degrees , P < 0.01 and 42.7% vs 57.3%, P < 0.01). The wedging of vertebrae was significantly higher in group B than in group A (50.1 degrees +/- 5.1 degrees vs 26.7 degrees +/- 2.7 degrees , P < 0.01). Additionally, correlation analysis revealed a significant correlation between the apical vertebral wedging angle and GK (R = 0.850, P = 0.001).Various disc and vertebral wedging exist in thoracolumbar kyphosis secondary to AS. The discs wedging contributes more to the thoracolumbar kyphosis in patients with GK < 70 degrees than vertebral wedging, whereas vertebral wedging is more conducive to the thoracolumbar kyphosis in patients with GK >= 70 degrees , indicating different biomechanical pathogenesis in varied severity of thoracolumbar kyphosis secondary to AS. PMID- 27661027 TI - Relationship between homocysteine and intraocular pressure in men and women: A population-based study. AB - The relationship between homocysteine levels and glaucoma has been questioned in previous studies without conclusive results. In the current study, we assessed the relationship between homocysteine levels and intraocular pressure which is one of the main factors in the development of glaucoma in men and women.A retrospective cross-sectional analysis of a database from a screening center in Israel which assessed 11,850 subjects, within an age range 20 to 80 years. The relationship between homocysteine and intraocular pressure has been investigated by comparing intraocular pressure in subjects with elevated and normal homocysteine and by comparing homocysteine levels in subjects with elevated and normal intraocular pressure. In addition, we compared the levels of homocysteine in subjects with and without a confirmed diagnosis of glaucoma.The mean IOP (+/ SD) in subjects with normal homocysteine levels(<=15 MUmol/L) was 13.2 +/- 2.3 mm Hg and 13.4 +/- 2.4 mm Hg in those with high homocysteine levels (>15 MUmol/L) (P < 0.008, 95% confidence interval [CI] 0.3-0.09).Nonetheless, after multivariate adjustment for age, gender, vitamin B12, and folic acid statistical significance was no longer demonstrated (P = 0.37). Mean homocysteine levels (+/-SD) in subjects with normal intraocular pressure of <= 21 mm Hg was 11.7 +/- 5.5 MUmol/L and 12.09 +/- 3.43 MUmol/L in those with elevated intraocular pressure (P = 0.4, 95%CI 1.1-1.8). Mean homocysteine levels (+/-SD) in subjects with glaucoma were 11.2 +/- 3.5 MUmol/L compared to 11.7 +/- 5.5 MUmol/L in subjects without glaucoma and normal intraocular pressure <= 21 mm Hg (P = 0.4, 95% CI 1.2 2.1).The current study displays no clinical correlation between the homocysteine level and the intraocular pressure. Homocysteine may not be used as a predictive parameter to recognize those subjects prone to develop elevated intraocular pressure. PMID- 27661028 TI - Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer: Retrospective cohort study, 7 year experience with 247 patients at the National Cancer Center in China. AB - To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT.A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center.Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47-0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32-0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04-0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment.Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID- 27661029 TI - A young infant with transient severe hypertriglyceridemia temporarily associated with meropenem administration: A case report and review of the literature. AB - BACKGROUND: Slight changes in the lipid profile can be observed over the acute phase of infectious diseases. Moreover, some anti-infective drugs can modify serum lipid concentrations, although antibiotics do not seem to have a relevant, direct, or acute effect on the lipid profile. METHODS: A 75-day-old breastfed Caucasian female, born at term after a regular pregnancy, was hospitalized for osteomyelitis. She was immediately treated with intravenous meropenem and vancomycin. Therapy was effective, but after 22 days of treatment, her blood was found to be viscous with a purple shade. RESULTS: A fasting blood sample showed serum triglycerides of 966 mg/dL, total cholesterol of 258 mg/dL, and high density lipoprotein cholesterol of 15 mg/dL. Secondary causes of hyperlipidemia and primary hereditary disorders were ruled out. Thereafter, the possibility that antibiotics may have had a role in the hypertriglyceridemia was considered, and meropenem was discontinued. After 72 hours of meropenem discontinuation, a sharp modification of lipid variables was observed, and further testing showed a complete normalization of the lipid profile. CONCLUSION: In this child with osteomyelitis, the increase in serum triglycerides appeared suddenly after 3 weeks of meropenem treatment and resolved quickly after meropenem discontinuation, thus highlighting the possible association between meropenem and lipid profile alterations. Monitoring the lipid profile should be considered in cases of long-term treatment with meropenem, and further studies on meropenem safety should include evaluation of the lipid profile. PMID- 27661030 TI - Does adding variceal status to the Child-Turcotte-Pugh score improve its performance in predicting mortality in cirrhosis? AB - The Child-Turcotte-Pugh (CTP) score is widely used worldwide to predict outcomes across a broad spectrum of liver diseases, mainly cirrhosis. Portal hypertension and variceal bleed are significant causes of morbidity and mortality in cirrhotic patients, although the variceal status is not incorporated into the classical CTP score. We sought to determine whether the inclusion of variceal status, specifically the Child-Turcotte-Pugh-Kumar (CTPK) score, would improve the utility of the classical CTP score to predict the clinical outcomes of cirrhotic patients in a single but high-volume center in China.We retrospectively analyzed the records of 253 patients from January 1, 2014 to December 31, 2014 and performed follow-up for at least 12 months. The CTPK score and the CTP score were obtained as soon as possible after the patient's admission. Telephone follow-up was performed to assess survival situations.At 3 and 12 months, the cumulative number of deaths was 9.1% (n = 23) and 13.8% (n = 35), respectively. In the multivariate Cox proportional hazards models, the CTPK score was independently associated with death within 3 and 12 months after adjusting for potential confounders. The predictive ability related to the 2 scores was evaluated by the area under the receiver operating characteristic curve (AUC-ROC) respectively. At 3 months of enrollment, the AUCs of CTPK and CTP were 0.814 and 0.838, respectively. At 12 months of enrollment, the AUCs of CTPK and CTP were 0.825 and 0.840, respectively. No significant difference between time points was observed. Both the CTPK score and the CTP score displayed prognostic value in cirrhotic patients, as the Kaplan-Meier analysis showed that the CTPK score could clearly discriminate patients in the intermediate term (P < 0.001).The CTPK score provides reliable prediction of mortality in Chinese cirrhotic patients for both short-term and medium-term prognoses, although it is not superior to the CTP score. Therefore, the CTP score remains an excellent tool for outcome prediction in patients with cirrhosis, and greater attention to variceal status may be in veins, even for patients with a history of variceal bleed or medium/large varices. PMID- 27661031 TI - Cutaneous fistulization of the hydatid disease: A PRISMA-compliant systematic review. AB - AIM: To provide an overview of the medical literature on cutaneous fistulization in patients with hydatid disease (HD). METHODS: According to PRISMA guidelines a literature search was made in PubMed, Medline, Google Scholar, and Google databases were searched using keywords to identify articles related to cutaneous fistulization of the HD. Keywords used were hydatid disease, hydatid cyst, cutaneous fistulization, cysto-cutaneous fistulization, external rupture, and external fistulization. The literature search included case reports, review articles, original articles, and meeting presentations published until July 2016 without restrictions on language, journal, or country. Articles and abstracts containing adequate information, such as age, sex, cyst size, cyst location, clinical presentation, fistula opening location, and management, were included in the study, whereas articles with insufficient clinical and demographic data were excluded. We also present a new case of cysto-cutaneous fistulization of a liver hydatid cyst. RESULTS: The literature review included 38 articles (32 full text, 2 abstracts, and 4 unavailable) on cutaneous fistulization in patients with HD. Among the 38 articles included in the study, 22 were written in English, 13 in French, 1 in German, 1 in Italian, and 1 in Spanish. Forty patients (21 males and 19 females; mean age +/- standard deviation, 54.0 +/- 21.5 years; range, 7-93 years) were involved in the study. Twenty-four patients had cysto-cutaneous fistulization (Echinococcus granulosus); 10 had cutaneous fistulization (E multilocularis), 3 had cysto-cutaneo-bronchio-biliary fistulization, 2 had cysto cutaneo-bronchial fistulization; and 1 had cutaneo-bronchial fistulization (E multilocularis). Twenty-nine patients were diagnosed with E granulosis and 11 had E multilocularis detected by clinical, radiological, and/or histopathological examinations. CONCLUSION: Cutaneous fistulization is a rare complication of HD. Complicated HD should be considered in the differential diagnosis of cases presenting with cutaneous fistulization, particularly in regions where HD is endemic. PMID- 27661032 TI - The number of retrieved lymph nodes needed for accurate staging differs based on the presence of preoperative chemoradiation for rectal cancer. AB - The aim of this study is to investigate if retrieval of 12 lymph nodes (LNs) is sufficient to avoid stage migration as well as to evaluate the prognostic impact of insufficient LN retrieval in different treatment settings of rectal cancer, particularly in the case of preoperative chemoradiotherapy (pCRT).The data of all patients with biopsy proven rectal adenocarcinoma who underwent curative surgery between January 2005 and December 2012 were analyzed. Univariate and multivariate analyses for oncologic outcomes were performed in LN metastasis or no LN metastasis (LN-) group. Subgroup analyses were performed according to whether a patient had received pCRT.A total of 1825 patients were enrolled into the study. The maximal Chi-square method revealed the minimum number of harvested LNs required to be 12. Univariate and multivariate analyses found LNs >= 12 to be an independent prognostic factor for both overall survival (OS) (hazard ratio [HR] = 0.5, 95% confidence intervals [CIs]: 0.3-0.8; P = 0.002) and disease-free survival (DFS) (HR = 0.6, 95% CI: 0.4-0.7; P < 0.001) in the LN- group. In the LN group, LNs >= 12 continued to be a significant prognostic factor both for OS and DFS in the subgroup of patients who did not undergo pCRT. However, in the subgroup of the LN- patients who underwent pCRT, LN >= 8 was significant for DFS and OS.Retrieval of LNs >= 12 and LNs >= 8 should be achieved to obtain accurate staging and optimal treatment for the non-pCRT and pCRT groups in rectal cancer, respectively. PMID- 27661033 TI - Prognostic role of pretreatment neutrophil-lymphocyte ratio in patients with diffuse large B-cell lymphoma treated with RCHOP. AB - This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR >= 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43-4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05 3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19-0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33-0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era. PMID- 27661035 TI - Delayed regaining of gait ability in a patient with brain injury: A case report. AB - BACKGROUND: Little is known about delay in regaining gait ability at a chronic stage after brain injury. In this study, we report on a single patient who regained the gait ability during 2 months of intensive rehabilitation starting 2 years after a brain injury. METHODS AND RESULTS: A 40-year-old male patient diagnosed with viral encephalitis underwent comprehensive rehabilitation until 2 years after onset. However, he could not even sit independently and presented with severe physical deconditioning and severe ataxia. To understand his neurological state, 4 neural tracts related to gait function were reconstructed, and based on the state of these neural tracts, we decided that the patient had the neurological potential to walk independently. Therefore, we assumed that the main reasons for gait inability in this patient were severe physical deconditioning and truncal ataxia. Consequently, the patient underwent the following intensive rehabilitative therapy: administration of drugs for control of ataxia (topiramate, clonazepam, and propranolol) and movement therapy for physical conditioning and gait training. As a result, after 2 months of rehabilitation, he was able to walk independently on an even floor, with improvement of severe physical deconditioning and truncal ataxia. CONCLUSION: We described the rehabilitation program in a single patient who regained the gait ability during 2 months of intensive rehabilitation starting 2 years after a brain injury. PMID- 27661034 TI - Long-term therapeutic outcome of ophthalmic complications following endoscopic sinus surgery. AB - Ophthalmic complications associated with endoscopic sinus surgery (ESS) are quite rare. There is a paucity of reliable data and limited experience on the clinical findings and treatments of these injuries. Our study here is to characterize the types of orbital injury following ESS, in particular extraocular muscle injury, and to evaluate the long-term therapeutic outcomes as compiled from a relatively large sample of Chinese patients.A series of 27 patients (21 males and 6 females; mean age = 42.6 years, ranges: 10-60 years) were retrospectively reviewed. The mean duration of orbital complication was 6.6 months (ranges: 1 day to 24 months). The right eye was affected in 19 patients and the left in 8 patients. All patients had various extraocular muscle dysfunction, including contusion, oculomotor nerve damage, muscle entrapment, muscle transection, and muscle destruction. All patients subjected to strabismus surgery showed an obvious reduction in deviation. Three patients achieved orthophoria without any surgery during the period of observation. All patients displayed mild to complicated orbital hemorrhage that often disappeared within 2 weeks. Optic nerve injury occurred in 29.6% of patients and vision damage in these patients was often irreversible.All patients with ophthalmic complications after ESS had strabismus and extraocular muscle dysfunction. Timing and type of strabismus surgery performed depended on the severity and number of muscles involved as well as the type of injury. This surgery is less effective in cases of restriction factor adhesion and/or entrapment as compared to that of patients with other types of strabismus. Orbital hemorrhages were usually resolved spontaneously, but optic nerve injury was mostly irreversible. PMID- 27661036 TI - Chemotherapy against cancer during pregnancy: A systematic review on neonatal outcomes. AB - BACKGROUND: The concomitant incidence of cancer and pregnancy has increased in recent years because of the increase in maternal age at the time of the 1st pregnancy. The diagnosis of cancer in a pregnant woman causes ethical and therapeutic problems for both the patient and the physician. The main aim of this paper is to describe the available evidence concerning the short- and long-term neonatal impact of chemotherapy given to pregnant women. METHODS: The relevant publications in English were identified by a systematic review of MEDLINE and PubMed for the last 15 years. The search strategy included "cancer[Title/Abstract] OR tumor[Title/Abstract] AND pregnancy[Title/Abstract] OR pregnant[Title/Abstract] AND embryo[Title/Abstract] or fetus[Title/Abstract] or neonate[Title/Abstract] or newborn[Title/Abstract] or pediatric[Title/Abstract] or child[Title/Abstract] AND English[lang]." RESULTS: An analysis of the literature showed that only the administration of chemotherapy during the embryonic stage of conceptus is dangerous and can lead to the termination of the pregnancy. When the disease is diagnosed in the 2nd or 3rd trimester of gestation or when it is possible to delay the initiation of chemotherapy beyond the 14th week, the risk of severe problems for the fetus are low, and pregnancy termination is not required. CONCLUSION: Data regarding the final outcome of children who have received in utero chemotherapy seem reassuring. Only the administration in the embryonal stage of conceptus is dangerous and can lead to the termination of pregnancy. When the disease is diagnosed in the 2nd or 3rd trimester of gestation or when it is possible to delay the initiation of chemotherapy beyond the 14th week, the risk of severe problems for the fetus are low and pregnancy termination is not needed. Increased knowledge of how to minimize the risks of chemotherapy can reduce improper management including unnecessary termination of pregnancy, delayed maternal treatment, and iatrogenic preterm delivery. PMID- 27661037 TI - The incidence and risk of osteoporosis in patients with anxiety disorder: A Population-based retrospective cohort study. AB - The purpose of this study was to investigate the relationship between anxiety disorder (AD) and the subsequent development of osteoporosis.We conducted a population-based retrospective cohort analysis according to the data in the Longitudinal Health Insurance Database 2000 of Taiwan. We included 7098 patients in both the AD and no-anxiety cohort who were matched according to age and sex between January 1, 2000, and December 31, 2013. The incidence rate and the risk ratios (RRs) of subsequent new-onset osteoporosis were calculated for both cohorts. We used Cox proportional hazards models to assess the effect of AD. The Kaplan-Meier method was applied to estimate the cumulative osteoporosis incidence curves.The AD cohort consisted of 7098 patients, and the comparison cohort comprised the same matched control patients without anxiety. The risk of osteoporosis was higher in the AD cohort than in the comparison cohort. In addition, the incidence of newly diagnosed osteoporosis remained significantly increased in all of the stratified follow-up durations (0-1, 1-5, 5-10, >=10years). Patients with AD were 1.79 times more likely to get osteoporosis than those without AD. We also observed a significant increase in osteoporotic risk in AD patients who are comorbid with hypertension, diabetes mellitus, and chronic liver disease.The incidence of osteoporosis in Taiwan is associated with an a priori AD history. The risk ratios are the highest for osteoporosis within 1 year of AD diagnosis, but the risk remains statistically significant for >1 year. Clinicians should pay particular attention to osteoporotic comorbidities in AD patients. PMID- 27661038 TI - Ginseng for managing menopausal woman's health: A systematic review of double blind, randomized, placebo-controlled trials. AB - BACKGROUND: The aim of this systematic review was to update, complete, and critically evaluate the evidence from placebo-controlled randomized clinical trials (RCTs) of ginseng for managing menopausal women's health. METHODS: We searched the literature using 13 databases (MEDLINE, AMED, EMBASE, the Cochrane Library, 6 Korean Medical, and 3 Chinese Databases) from their inception to July 2016 and included all double-blind RCTs that compared any type of ginseng with a placebo control in postmenopausal women. The methodological quality of all studies was assessed using a Cochrane risk of bias tool. RESULTS: Ten RCTs met our inclusion criteria. Most RCTs had unclear risk of bias. One RCT did not show a significant difference in hot flash frequency between Korean red ginseng (KRG) and placebo. The second RCT reported positive effects of KRG on menopausal symptoms. The third RCT found beneficial effects of ginseng (Ginsena) on depression, well-being, and general health. Four RCTs failed to show significant differences in various hormones between KRG and placebo controls except dehydroepiandrosterone. Two other RCTs failed to show effects of KRG on endometrial thickness in menopausal women. The other RCT also failed to show the effects of American ginseng on oxidative stress markers and other antioxidant enzymes. CONCLUSION: Our systematic review provided positive evidence of ginseng for sexual function and KRG for sexual arousal and total hot flashes score in menopausal women. However, the results of KRG or ginseng failed to show specific effects on hot flash frequency, hormones, biomarkers, or endometrial thickness. The level of evidence for these findings was low because of unclear risk of bias. PMID- 27661039 TI - The Pemberton Happiness Index: Validation of the Universal Portuguese version in a large Brazilian sample. AB - The Pemberton Happiness Index (PHI) is a recently developed integrative measure of well-being that includes components of hedonic, eudaimonic, social, and experienced well-being. The PHI has been validated in several languages, but not in Portuguese. Our aim was to cross-culturally adapt the Universal Portuguese version of the PHI and to assess its psychometric properties in a sample of the Brazilian population using online surveys.An expert committee evaluated 2 versions of the PHI previously translated into Portuguese by the original authors using a standardized form for assessment of semantic/idiomatic, cultural, and conceptual equivalence. A pretesting was conducted employing cognitive debriefing methods. In sequence, the expert committee evaluated all the documents and reached a final Universal Portuguese PHI version. For the evaluation of the psychometric properties, the data were collected using online surveys in a cross sectional study. The study population included healthcare professionals and users of the social network site Facebook from several Brazilian geographic areas. In addition to the PHI, participants completed the Satisfaction with Life Scale (SWLS), Diener and Emmons' Positive and Negative Experience Scale (PNES), Psychological Well-being Scale (PWS), and the Subjective Happiness Scale (SHS). Internal consistency, convergent validity, known-group validity, and test-retest reliability were evaluated. Satisfaction with the previous day was correlated with the 10 items assessing experienced well-being using the Cramer V test. Additionally, a cut-off value of PHI to identify a "happy individual" was defined using receiver-operating characteristic (ROC) curve methodology.Data from 1035 Brazilian participants were analyzed (health professionals = 180; Facebook users = 855). Regarding reliability results, the internal consistency (Cronbach alpha = 0.890 and 0.914) and test-retest (intraclass correlation coefficient = 0.814) were both considered adequate. Most of the validity hypotheses formulated a priori (convergent and know-group) was further confirmed. The cut-off value of higher than 7 in remembered PHI was identified (AUC = 0.780, sensitivity = 69.2%, specificity = 78.2%) as the best one to identify a happy individual.We concluded that the Universal Portuguese version of the PHI is valid and reliable for use in the Brazilian population using online surveys. PMID- 27661040 TI - Lead poisoning in a 16-year-old girl: a case report and a review of the literature (CARE compliant). AB - BACKGROUND: Lead is a toxic element of the environment which leads to major complications once it enters the blood stream, affecting multiple organs and systems of the body. METHODS: We present the case of a 16-year-old girl, diagnosed with lead poisoning after occupational exposure due to the fact that the girl was actively involved in the family's pottery business.History revealed that the girl participated in the process of pottery, her father was also diagnosed with lead poisoning 2 years before. The patient's personal history underlined that approximately 1 year ago she presented with severe abdominal pain, being diagnosed with acute appendicitis and she underwent appendectomy, but the pain persisted, thus due to family history of lead poisoning, the suspicion of saturnine colic rose, and she was diagnosed with lead poisoning. The main symptoms and signs were severe abdominal pain, vomiting, and arterial hypertension. The clinical evolution was favorable under symptomatic treatment and chelation therapy. RESULTS: Lead toxicity is a life-threatening condition because of its severe acute and chronic complications. In children, there is no safe blood lead level, prevention methods are, therefore, very important in order to avoid toxic multiorganic effects of this metal. CONCLUSION: Even though the diagnosis of lead poisoning remains difficult in children, it must also be taken into consideration by the clinician facing a child with gastrointestinal or neurological involvement. PMID- 27661041 TI - Cancer-specific incidence rates of tuberculosis: A 5-year nationwide population based study in a country with an intermediate tuberculosis burden. AB - Population-based studies of the incidence of tuberculosis in cancer patients according to the type of cancer are limited. We investigated the cancer-specific incidence of tuberculosis in a nationwide population-based cohort in a country with an intermediate burden of tuberculosis.We used mandatory National Health Insurance claims data to construct a cancer cohort of adults (aged 20-99 years) with newly diagnosed malignancies other than lung cancer, from January 2008 to December 2012. Patients who developed tuberculosis in this period were identified in the cancer cohort and the general population. Standardized incidence ratios (SIRs) of tuberculosis in the cancer cohort according to type of cancer and time after cancer diagnosis were calculated by comparing the observed incidence rates with those inferred from the age- and gender-specific incidence rates in the general population.A total of 855,382 cancer patients and 1589,876 person-years (py) were observed. A total of 5745 patients developed tuberculosis; the mean incidence rate was 361.3 per 100,000 py, and the SIR was 2.22 (95% confidence interval [CI], 2.17-2.27). The incidence rate was highest for hematologic malignancy and lowest for thyroid cancer. It was also highest as 650.1 per 100,000 py, with SIR of 3.70 (CI, 3.57-3.83) for the first 6 months after diagnosis of malignancy and then declined. However, it still remained higher than that of the general population after 24 months (SIR = 1.43, CI, 1.36-1.51).The incidence of tuberculosis increases after diagnosis in patients with malignancies. The risk of tuberculosis differs according to the type of cancer and remains elevated even 24 months after cancer diagnosis. Tuberculosis should be considered an important comorbidity in patients with malignancies. PMID- 27661043 TI - Utility of the 2006 Sendai and 2012 Fukuoka guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas: A single-center experience with 138 surgically treated patients. AB - This study aimed to evaluate the utility of the 2006 Sendai and 2012 Fukuoka guidelines for differentiating malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas from benign IPMN.Between January 2000 and March 2015, a total of 138 patients underwent surgery and had a pathologically confirmed pancreatic IPMN. Clinicopathological parameters were reviewed, and all patients were classified according to both the 2006 Sendai and 2012 Fukuoka guidelines. Univariate and multivariate analyses were used for identifying significant factors associated with malignancy in IPMN.There were 9 high-grade dysplasia (HGD) and 37 invasive cancers (ICs) in the 138 patients. The positive predictive value (PPV) and negative predictive value (NPV) of the Sendai and Fukuoka guidelines for HGD/IC was 35.1%, 43.3%, 100%, and 85.4%, respectively. Of the 36 patients with worrisome features using the Fukuoka guideline, 7 patients had HGD/IC in their IPMNs. According to the multivariate analysis, jaundice, tumors of >=3 cm, presence of mural nodule on imaging, and aged <65 years were associated with HGD/IC in patients with IPMN.The Sendai guideline had a better NPV, but the Fukuoka guideline had a better PPV. We suggest that patients with worrisome features based on the Fukuoka guideline be aggressively managed. PMID- 27661042 TI - Distribution of lung blood on modified bilateral Glenn shunt evaluated by Tc-99m MAA lung perfusion scintigraphy: A retrospective study. AB - The aim of the present study was to determine the distribution of lung blood in a modified bilateral Glenn procedure designed in our institute with lung perfusion scintigraphy. Sixteen consecutive patients who underwent modified bilateral Glenn operation from 2011 to 2014 were enrolled in the study. The control group consisted of 7 patients who underwent bidirectional Glenn shunt. Radionuclide lung perfusion scintigraphy was performed using Tc-99m-macro aggregated albumin (MAA) in all patients. For the patients in modified bilateral Glenn group, the time at which the radioactivity accumulation peaked did not differ significantly between the right and left lung field (t = 0.608, P = 0.554). The incidence of perfusion abnormality in each lung lobe also did not differ significantly (P = 0.426 by Fisher exact test). The radioactive counts were higher in the right lung than in the left lung, but the difference was not statistically significant (t = 1.502, P = 0.157). Radioactive perfusion in the lower lung field was significantly greater than that in the upper field (t = 4.368, P < 0.001). Compared with that in the bidirectional Glenn group, the ratio of radioactivity in the right lung to that in left lung was significantly lower in the modified bilateral Glenn group (t = 3.686, P = 0.002). Lung perfusion scintigraphy confirmed the benefit of the modified bilateral Glenn shunt with regard to more balanced blood perfusion in both lungs. PMID- 27661044 TI - Trends of spinal tuberculosis research (1994-2015): A bibliometric study. AB - BACKGROUND: Spinal tuberculosis is the most common form of skeletal tuberculosis. However, there were limited data to evaluate the trend of spinal tuberculosis research. This study aims to investigate the trend of spinal tuberculosis research and compare the contribution of research from different countries and authors. METHODS: Spinal tuberculosis-related publications from 1994 to 2015 were retrieved from the Web of Science database. Excel 2013, GraphPad Prism 5, and VOSviewer software were used to analyze the search results for number of publications, cited frequency, H-index, and country contributions. RESULTS: A total of 1558 papers were identified and were cited 16,152 times as of January 25, 2016. The United States accounted for 15.1% of the articles, 22.3% of the citations, and the highest H-index (33). China ranked third in total number of articles, fifth in citation frequency (815), and ranked seventh in H-index (13). The journal Spine (IF 2.297) had the highest number of publications. The author Jain A.K. has published the most papers in this field (20). The article titled "Tuberculosis of the spine: Controversies and a new challenge" was the most popular article and cited a total of 1138 times. The keyword "disease" was mentioned the most for 118 times and the word "bone fusion" was the latest hotspot by 2015. CONCLUSION: Literature growth in spinal tuberculosis is slowly expanding. Although publications from China are increasing, the quality of the articles still requires improvements. Meanwhile, the United States continues to be the largest contributor in the field of spinal tuberculosis. According to our bibliometric study, bone fusion may be an emerging topic within spinal tuberculosis research and is something that should be closely observed. PMID- 27661045 TI - Giant right coronary artery aneurysms presenting as a cardiac mass: Case report. AB - INTRODUCTION: Coronary artery aneurysm (CAA) is defined as coronary dilatation which exceeds the diameter of the normal adjacent artery segments or the diameter of the patient's largest coronary artery by 1.5 times. The incidence of giant CAA is difficult to be determined, since only few reports have been described in the literature. METHODS AND RESULTS: A 65-year-old man was referred to our hospital because of a "mass" in the right heart detected on echocardiography at a regular medical health examination, while he experienced no any symptoms. Coronary angiography showed the severe stenosis of the left anterior descending artery (LAD) and the left circumflex artery (LCX) and the diffusely ectatic change of the right coronary artery (RCA), but no mass was found in any of these arteries. Coronary computed tomography angiography (CTA) confirmed that the "mass" was the giant aneurysms of RCA with thrombus. He received coronary artery bypass graft (CABG) with thrombectomy. The histopathology showed the deposits of lipid and hyalin in the tunica intima, the focal calcifications, the very thin tunica media, and the disappearance of the part of the tunica media in the RCA. CONCLUSIONS: Coronary artery aneurysm which may contain thrombus can complicate a diagnostic coronary angiography due to the risk of distal embolization and may lead to myocardial infarction. This case report demonstrates 2 RCA aneurysms with a thrombus presenting as a giant "mass" which was successfully treated by CABG with thrombectomy. PMID- 27661046 TI - Comparison of the incidence of emergence agitation and emergence times between desflurane and sevoflurane anesthesia in children: A systematic review and meta analysis. AB - BACKGROUND: The differences in the incidence and severity of emergence agitation (EA) and emergence times between desflurane and sevoflurane anesthesia have not been as clearly elucidated in children as in adults. METHODS: The design of the study is a systematic review with meta-analysis of randomized controlled trials. The study methodology is based on the Cochrane Review Methods. A comprehensive literature search was conducted to identify clinical trials comparing the incidence or severity of EA and emergence times in children anesthetized with desflurane or sevoflurane. Two reviewers independently assessed each study according to predefined inclusion criteria and extracted data from each study using a prespecified data extraction form. The data from each study were combined using a fixed effect or random effect model to calculate the pooled risk ratio (RR) or standardized mean difference (SMD) and 95% confidence interval (CI). Funnel plots were used to assess publication bias. Subgroup and sensitivity analyses were performed. RESULTS: Fourteen studies met the inclusion criteria. Among the 1196 patients in these 14 studies, 588 received desflurane anesthesia and 608 received sevoflurane anesthesia. The incidence of EA was comparable between the 2 groups (pooled RR = 1.21; 95% CI: 0.96-1.53; I = 26%), and so was the severity of EA (EA score) between the 2 groups (SMD = 0.12; 95% CI: -0.02 to 0.27; I = 0%). Extubation and awakening times were shorter in the desflurane group than in the sevoflurane group; the weighted mean differences were -2.21 (95% CI: -3.62 to -0.81; I = 93%) and -2.74 (95% CI: -3.80 to -1.69; I = 85%), respectively. No publication bias was found in the funnel plot. The subgroup analysis based on the type of EA scale showed a higher incidence of EA in the desflurane group than in the sevoflurane group in studies using 3-, 4-, or 5 point EA scales; the pooled RR was 1.38 (95% CI: 1.10-1.73; I = 37%). CONCLUSION: The incidence and severity of EA were comparable between desflurane and sevoflurane anesthesia in children; however, emergence times, including extubation and awakening times, were shorter in desflurane anesthesia. PMID- 27661047 TI - Teflon-buttressed sutures plus pericardium patch repair left ventricular rupture caused by radiofrequency catheter ablation: A case report. AB - BACKGROUND: Cardiac rupture often occurs after myocardial infarction or chest trauma with a high mortality rate. However, left ventricular rupture caused by radiofrequency catheter ablation (RFCA) is extremely rare. METHODS: We describe a case of a 61-year-old male who survived from left ventricular rupture caused by a RFCA procedure for frequent ventricular premature contractions. Surgical exploration with cardiopulmonary bypass (CPB) was performed when the signs of cardiac tamponade developed 7 hours after the ablation surgery. RESULTS: Teflon buttressed sutures of the tear in the left ventricular posterolateral wall and pericardium patch applied to the contusion region on the wall repaired the rupture safely and effectively. CONCLUSION: Timely surgical intervention under CPB facilitated the survival of the patient. Teflon-buttressed sutures plus pericardium patch achieved the successful repair of the rupture. PMID- 27661048 TI - Autograft versus allograft in anterior cruciate ligament reconstruction: A meta analysis with trial sequential analysis. AB - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is considered as the standard surgical procedure for the treatment of ACL tear. However, there is a crucial controversy in terms of whether to use autograft or allograft in ACL reconstruction. The purpose of this meta-analysis is to compare autograft with allograft for patients undergoing ACL reconstruction. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials that compared autograft with allograft in ACL reconstruction up to January 31, 2016. The relative risk or mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. The risk of bias for individual studies according to the Cochrane Handbook. The trial sequential analysis was used to test the robustness of our findings and get more conservative estimates. RESULTS: Thirteen trials were included, involving 1636 participants. The results of this meta-analysis indicated that autograft brought about lower clinical failure, better overall International Knee Documentation Committee (IKDC) level, better pivot-shift test, better Lachman test, greater Tegner score, and better instrumented laxity test (P < 0.05) than allograft. Autograft was not statistically different from allograft in Lysholm score, subjective IKDC score, and Daniel 1-leg hop test (P > 0.05). Subgroup analyses demonstrated that autograft was superior to irradiated allograft for patients undergoing ACL reconstruction in clinical failure, Lysholm score, pivot-shift test, Lachman test, Tegner score, instrumented laxity test, and subjective IKDC score (P < 0.05). Moreover, there were no significant differences between autograft and nonirradiated allograft. CONCLUSIONS: Autograft is superior to irradiated allograft for patients undergoing ACL reconstruction concerning knee function and laxity, but there are no significant differences between autograft and nonirradiated allograft. However, our results should be interpreted with caution, because the blinding methods were not well used. PMID- 27661049 TI - Feasibility of laparoscopic major hepatectomy for hepatic paragonimiasis: two case reports. AB - BACKGROUND: Though accumulated evidence proved that laparoscopic major hepatectomy was technically feasible, it remains a challenging procedure and is limited to highly specialized centers. Paragonimiasis is one of the most important food-borne parasitic zoonoses caused by the trematode of the genus Paragonimus. Although hepatic paragonimiasis is rare, the previous studies had investigated hepatic paragonimiasis from different perspectives. However, the safety and feasibility of laparoscopic major hepatectomy for hepatic paragonimiasis have not yet been reported in the literature. METHODS: We here present 2 cases of hepatic paragonimiasis at the deep parts of the liver with treatment by laparoscopic major hepatectomy. One case is a 32-year-old male patient who was admitted to the hospital due to upper abdominal discomfort without fever for 1 month. The clinical imaging revealed that there was a lesion about 5.9 * 3.7 cm in the boundary of right anterior lobe and right posterior lobe of the liver with rim enhancement and tract-like nonenhanced areas. The other one is a 62-year-old female patient who was referred to the hospital for 1 month of right upper abdominal pain and fever. The ultrasonography showed that there was a huge hypoechoic mass (about 10.8 * 6.3 cm) in middle lobe of the liver with tract-like nonenhanced areas. Both patients were from an endemic area of paragonimiasis and the proportion of eosinophil in the second case was increased. RESULTS: The preoperative diagnosis of the first case was ambiguous and the hepatic paragonimiasis was considered for the second case. The first case underwent laparoscopic extended right posterior lobe hepatectomy and the other case underwent laparoscopic extended left hemihepatectomy. Both operations went very well and the operation times for the 2 cases were 275 minutes and 310 minutes, respectively. The 2 patients' postoperative recovery was smooth without major postoperative complications (such as, bleeding, bile leakage, and liver failure). Moreover, the 2 patients were discharged on the 6th day and 7th day after surgery, respectively. The postoperative histopathological examination manifested hepatic paragonimiasis in both patients. CONCLUSION: This study suggests that the laparoscopic approach may be safe and technically feasible for hepatic paragonimiasis. PMID- 27661051 TI - Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival: A case report and literature review. AB - BACKGROUND: Malignant phyllodes tumor (PT) is a rare fibro epithelial neoplasm of the breast, which is poor prognosis due to high risk of recurrence and distant metastasis. METHODS: We report a case of malignant PT. It had recurred locally five times, and the sixth relapse was occurred 54 months after first diagnosis, presenting a huge pelvic mass (14 cm * 11 cm) by CT scan. Histopathological examination has demonstrated a metastatic phyllodes tumor. After postoperative chemotherapy treatment, a longer survival has been achieved, which is more than 72 months. RESULTS: Our case report describes a breast PT with several local recurrences and a rare metastasis (pelvic cavity), but long-term overall survival was achieved after surgery and chemotherapy. CONCLUSION: We conclude that trustworthy prognosticators that identify patients with excessive potential of aggressive clinical course should be explored. Moreover, proper treatment could prolong overall survival of metastatic PT patients. PMID- 27661050 TI - Splenic abscess owing to cancer at the splenic flexure: A case report and comprehensive review. AB - BACKGROUND: The cancer of the splenic flexure of the colon is a rare medical entity with severe morbidity because of its insidious onset. METHODS: We present the case of a 59-year-old male patient with dull left upper quadrant pain, leukocytosis, and anemia. A splenic abscess described as an air-fluid level with splenocolic fistula was found on CT scan imaging. Surgery was done for splenic pus drainage. He was again admitted 2 months later for intestinal obstruction. RESULTS: An exploratory laparotomy showed multiple hard, gray liver nodules as well as a hard mass in the small bowel. Owing to extensive adhesions and a late stage of cancer involvement, the splenic flexure tumor was not resected. A loop transverse colostomy was done and a Coloplast Colostomy bag placed. We also reviewed the literature-linking colon cancer and splenic abscess with specific attention to the carcinoma of the splenic flexure. As the latter invades through the spleen matter, there is the creation of a splenocolic fistula, which allows the migration of normal gut flora into the spleen. This leads to the formation of the splenic abscess. CONCLUSION: This is the 13 case report pertaining to invading colonic cancer causing a splenic abscess. Although the treatment for splenic abscesses is shifting from splenectomy to image-guided percutaneous pus drainage, the few reported cases make the proper management of such complication still unclear. PMID- 27661052 TI - STROBE-compliant article: Is continuity of care associated with avoidable hospitalization among older asthmatic patients? AB - Continuity of care (COC) has a proven relationship with health care outcomes. However, evidence regarding an association between COC and avoidable hospitalization for elderly patients with asthma is insufficient.A retrospective cohort study was performed using Taiwanese National Health Insurance claim data from 2004 to 2013. Patients were retrospectively followed for 2 years; the COC index (COCI) for asthma was measured in the 1st year, and avoidable hospitalization for asthma and follow-up time were determined in the subsequent year. Cox proportional hazards regression was employed to examine hazard ratios (HRs) between COC and avoidable hospitalization for asthma after adjustment for confounding factors. Adjusted HR (aHR) was also calculated by stratifying each variable to investigate whether the effect of COC on hospitalization for asthma was avoidable and how this varied across levels of COCI.Of 3356 patients included in this study, 1648 patients (49%) had a COCI of 1, and the average COCI was 0.73. Compared with patients with high COC (COCI = 1), those with low COC (COCI < 0.5) had a significantly higher risk of avoidable hospitalization for asthma (aHR = 2.68; 95% confidence interval [CI]: 1.55-4.63). In addition, after stratified analysis, we determined that COC plays a much more important role for patients who were women, had low insurance premiums, and had no comorbidities.High continuity of ambulatory asthma care is linked to a reduced risk of avoidable hospitalization for asthma in elderly asthmatic patients. PMID- 27661053 TI - Transcendence, religion and spirituality in medicine: Medical students' point of view. AB - To explore how medical students-the doctors of tomorrow-reflect upon meeting the spiritual needs of their patients, and whether they have reflected on their own religious or spiritual beliefs, or not. The study also investigates to what extent the students feel comfortable with addressing spiritual issues in their patient care, and whether they feel this is beyond their role as medical doctors.A self-administered questionnaire was developed. The survey was administered in teaching classes at the medical university of Vienna. One thousand four hundred (836 women and 564 men) students responded, laying the foundation for a thorough statistical analysis.59.5% of the students had reflected on their own belief concepts, 21.9% consider themselves religious, and 20.1% see themselves as spiritual individuals. 75.6% of the students agreed with the statement that religious conviction/spirituality might have an effect on how cancer patients cope. 85.9% would consider talking with their patients about religious/spiritual issues if patients wish to do so. 86.3% would involve chaplains if they feel it is necessary.The results of this study suggest that future doctors want to see the patient in a wider scope than the bio-psycho social one, by including the meta-dimension of transcendence. PMID- 27661054 TI - The Effects of CYP2C19 genotype on the susceptibility for nephrosis in cardio cerebral vascular disease treated by anticoagulation. AB - In recent years, the genetic factor has become one of the important predisposing factors of nephropathy susceptibility. There is a high incidence of nephropathy in CCVd. The CYP2C19 enzyme metabolizes most the drugs, including proton pump inhibitors commonly used medicines to treat CCVd, CYP2C19 genetic polymorphisms is association with multi-pathogenesis factors of nephropathy. The purpose of the study is to reveal the association between CYP2C19 genotype and the susceptibility of nephropathy in the CCVd patients. The study is composed of 623 samples from CCVd treated by anticoagulation. The patients were studied, including CCVd with hyperuricemia, coronary heart disease, diabetes, and other complication. Biochemical tests and CYP2C19 variants measurements were performed by the gene chip method. The association among CYP2C19 variants, complications, and nephropathy was analyzed in the CCVd. There is no correlation between nephropathy and complications in CCVd. In hyperuricemia, coronary heart disease and diabetes groups, the differences of renal function tests were significant between CYP2C19 mutant (P < 0.05). The nephropathy risk of wild genotype is 3.288 times higher than of mutation genotype in hyperuricemic group, 1.928 times higher than mutation genotype in coronary heart disease group, and 5.248 times higher than CYP2C19 mutation genotype in the diabetic group. There was significant correlation between the CYP2C19 wild type and the nephropathy susceptibility in CCVd patients. The CYP2C19 gene plays a potential maker to evaluate nephropathy in CCVd patients. We deduced that identification of CYP2C19 gene type may benefit for reducing and avoiding nephropathy caused by abnormal metabolism function in CCVd patients. PMID- 27661056 TI - Two case reports: Whole genome sequencing of two clinical macrolide-resistant Mycoplasma pneumoniae isolates with different responses to azithromycin. AB - BACKGROUND: Cases of macrolide-resistant Mycoplasma pneumoniae have increased rapidly since 2000, especially in Asia. Patients infected with macrolide resistant M pneumoniae usually present with severe M pneumoniae pneumonia. The aim of this study was to identify indicators for whether children at an early stage of M pneumoniae infection develop mild or severe pneumonia. CASE SUMMARY: Herein, we retrospectively reviewed 2 pediatric cases caused by macrolide resistant M pneumoniae, but with markedly different severity of pneumonia. First, we compared the clinical courses of the patients, then isolated the pathogens and tested their response to macrolides, then finally, carried out whole genome sequencing of these isolates. Despite the difference in clinical presentation of the infection, both isolates exhibited a high level of resistance to macrolide antibiotics. Analysis of clinical data showed that the erythrocyte sedimentation rate in blood samples of the patients in the early stages of disease varied greatly. Genome sequence analysis revealed single nucleotide polymorphisms mainly focused on adhesin P1, which is involved in the pathogenicity of M pneumoniae. CONCLUSION: The differences of erythrocyte sedimentation rate in the early stage of M pneumoniae pneumonia and mutations in P1 protein may help us to distinguish between severe or mild disease after infection with macrolide-resistant M pneumoniae. These findings could lead to the development of screening assays that will allow us to distinguish severe or mild M pneumoniae pneumonia early. PMID- 27661055 TI - Increases in perinatal mortality in prefectures contaminated by the Fukushima nuclear power plant accident in Japan: A spatially stratified longitudinal study. AB - Descriptive observational studies showed upward jumps in secular European perinatal mortality trends after Chernobyl. The question arises whether the Fukushima nuclear power plant accident entailed similar phenomena in Japan. For 47 prefectures representing 15.2 million births from 2001 to 2014, the Japanese government provides monthly statistics on 69,171 cases of perinatal death of the fetus or the newborn after 22 weeks of pregnancy to 7 days after birth. Employing change-point methodology for detecting alterations in longitudinal data, we analyzed time trends in perinatal mortality in the Japanese prefectures stratified by exposure to estimate and test potential increases in perinatal death proportions after Fukushima possibly associated with the earthquake, the tsunami, or the estimated radiation exposure. Areas with moderate to high levels of radiation were compared with less exposed and unaffected areas, as were highly contaminated areas hit versus untroubled by the earthquake and the tsunami. Ten months after the earthquake and tsunami and the subsequent nuclear accident, perinatal mortality in 6 severely contaminated prefectures jumped up from January 2012 onward: jump odds ratio 1.156; 95% confidence interval (1.061, 1.259), P value 0.0009. There were slight increases in areas with moderate levels of contamination and no increases in the rest of Japan. In severely contaminated areas, the increases of perinatal mortality 10 months after Fukushima were essentially independent of the numbers of dead and missing due to the earthquake and the tsunami. Perinatal mortality in areas contaminated with radioactive substances started to increase 10 months after the nuclear accident relative to the prevailing and stable secular downward trend. These results are consistent with findings in Europe after Chernobyl. Since observational studies as the one presented here may suggest but cannot prove causality because of unknown and uncontrolled factors or confounders, intensified research in various scientific disciplines is urgently needed to better qualify and quantify the association of natural and artificial environmental radiation with detrimental genetic health effects at the population level. PMID- 27661058 TI - Ocular manifestation in myeloid/NK cell precursor acute leukemia: a case report. Diagnosed by flow cytometry and PCR from aqueous humor. AB - BACKGROUND: Myeloid/NK cell precursor acute leukemia (MNKL) is a rare type of leukemia, and ocular complications have not previously been reported. We now report a patient with MNKL who developed intraocular infiltrates during follow up. METHODS AND RESULTS: A 13-year-old boy diagnosed with MNKL developed left eye pain 3 months after starting treatment. Examination of the left eye revealed a visual acuity of counting fingers at 20 cm, ciliary hyperemia, small corneal keratic precipitates, hypopyon, grade 4 vitreous opacities, and an obscured fundus. The differential diagnosis was between an opportunistic infection associated with immunodeficiency and an intraocular leukemic cell infiltrate. Therefore, a sample of aqueous humor was aspirated. Multiplex PCR/broad-range PCR of the aqueous humor was below detection limits for viruses, bacteria, and fungi. Flow cytometry (FCM) detected NK-related CD56-positive cells, thus leading to a diagnosis of ocular infiltrates due to MNKL. With treatment of the ocular infiltrates by consolidation systemic chemotherapy including intrathecal methotrexate (MTX), there was clearing of the vitreous opacities; and optic disc swelling, retinal hemorrhages, exudates, and protuberant lesions were now seen. With the addition of local radiation therapy to the eye, there was a dramatic treatment response, with regression of the optic disc findings and retinal lesions, and an improved visual acuity of 1.5. CONCLUSION: We encountered the first case of MNKL in which ocular infiltrates developed during follow-up. Multiplex PCR and FCM of the aqueous humor were useful in rapidly distinguishing leukemic cell infiltrates from an opportunistic infection. This case highlights the usefulness of intrathecal MTX and local radiotherapy in treating ocular infiltrates in patients with MNKL. PMID- 27661057 TI - Enchondroma in the distal phalanx of the finger: An observational study of 34 cases in a single institution. AB - The goal of our study was to report the clinical presentation, treatment, and complications of enchondroma in the distal phalanx of the finger. This was a retrospective study of 34 patients (19 women and 15 men) who underwent surgery between May 2004 and September 2012 for enchondroma in the distal phalanx of the finger. The average age of the patients was 39.38 +/- 10.97 years old (range 14 59). The presenting symptoms and imaging features were recorded. The surgical procedure was performed under regional or general anesthesia. The surgical technique involved removal of tumors by opening a cortical window and curetting the cavity. The defects were filled with an injectable calcium phosphate cement. All patients received follow-up in our outpatient clinic every 6 months. Expansion of bone or thinning of the cortex present in the radiological imaging, including anteroposterior and lateral plain radiographs of the fingers, was used to assess for tumor recurrence. The observational end-point was reoperation.All tumors were confirmed as enchondromas by the pathological results. None of the patients had a tumor recurrence. Three patients (9% of cases) developed an infection. After antibiotic treatment, 2 patients were cured, and 1 patient required an amputation. Enchondroma in the distal phalanx of the finger presents with a variety of clinical symptoms. Injectable calcium phosphate cement is adequate for bone grafting. Postoperative infection is more common than tumor recurrence. If patients have an infection or bilateral bone cortex defects, bone grafting is challenging. LEVEL OF EVIDENCE: Therapeutic study, Level IV. PMID- 27661059 TI - Three Short Stories about Hexaarylbenzene-Porphyrin Scaffolds. AB - A feasible two-step synthesis and characterization of a full series of hexaarylbenzene (HAB) substituted porphyrins and tetrabenzoporphyrins is presented. Key steps represent the microwave-assisted porphyrin condensation and the statistical Diels-Alder reaction to the desired HAB-porphyrins. Regarding their applications, they proved to be easily accessible and effective high molecular mass calibrants for (MA)LDI mass spectrometry. The free-base and zinc(II) porphyrin systems, as well as the respective tetrabenzoporphyrins, demonstrate in solid state experiments strong red- and near-infrared-light emission and are potentially interesting for the application in "truly organic" light-emitting devices. Lastly, they represent facile precursors to large polycyclic aromatic hydrocarbon (PAH) substituted porphyrins. We prepared the first tetra-hexa-peri-hexabenzocoronene substituted porphyrin, which represents the largest prepared PAH-porphyrin conjugate to date. PMID- 27661061 TI - Scientific Poster Abstracts Selected for the 2016 Congress on Atherosclerotic Cardiovascular Disease Prevention, Sept. 16-18, 2016, Boca Raton, Florida. PMID- 27661060 TI - Cytochrome P450 2C9 gene polymorphism and warfarin maintenance dosage in pediatric patients: A systematic review and meta-analysis. AB - AIM: To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement. METHODS: A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria. Required data were extracted, and researchers were consulted for additional data if needed. Review Manager version 5.2.3 software was used to analyze the relationship between CYP2C9 polymorphisms and warfarin maintenance doses in pediatric patients. Eight articles with a combined total of 507 pediatric patients were included in the meta-analysis. RESULTS: Maintenance warfarin doses in patients with CYP2C9 *1/*2 genotype, CYP2C9 *1/*3 genotype, and CYP2C9 variant carriers which contain at least one variant allele (*2 or *3) were from 15% to 41% lower than doses in patients with the wild-type allele (CYP2C9 *1/*1): All differences were significant with P-values <.05. The Fontan procedure as a medical indication for anticoagulation was also associated with a lower warfarin maintenance dose; however, target INR range was not. CONCLUSIONS: We found that CYP2C9 gene polymorphism (referring to the presence of *1/*2, *1/*3, and variant genotypes in the population in addition to the wild type) was significantly associated with decreased warfarin maintenance dose requirements. Additionally, a specific indication for warfarin, the Fontan procedure, was associated with a lower daily warfarin dose. However, the results of our study require confirmation from more research with larger numbers of pediatric patients. PMID- 27661062 TI - G Protein-Coupled Receptor Endosomal Signaling and Regulation of Neuronal Excitability and Stress Responses: Signaling Options and Lessons From the PAC1 Receptor. AB - Our understanding of G protein coupled receptor (GPCR) mechanisms and functions have evolved considerably. Among the many conceptual realignments, GPCRs can exist in an ensemble of active microstates that have the potential to differentially engage specific downstream signaling events. Furthermore, among GPCR dynamics, GPCR internalization and vesicular trafficking are no longer solely mechanisms for desensitization, but now appreciated to form intricate endosomal signaling complexes that can potentially target second messengers to intracellular compartments with high temporal and spatial resolution. The PACAPergic system is important in the maintenance of physiological homeostasis in the central and peripheral nervous systems and activation of the PACAP-selective PAC1 receptor can generate differential but coordinate plasma membrane and endosomal signals for cellular responses. The integration of these signals can modulate PACAP-induced changes in ionic conductances that gate neuronal excitability. PACAP/PAC1 receptor generation of endosomal ERK signals participate in chronic pain and anxiety-like responses which can be attenuated with endocytosis inhibitors. From the abilities of ligands to stabilize the different GPCR microstates for biased downstream signaling, the development of biased PAC1 receptor agonists and antagonists may provide opportunities to dissociate the homeostatic regulatory signals of PACAP from the maladaptive effects. In particular, the development of biased antagonists to PAC1 receptor-mediated endosomal signaling may offer therapeutic options for chronic pain and stress related disorders. J. Cell. Physiol. 232: 698-706, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27661063 TI - Parapatric genetic introgression and phenotypic assimilation: testing conditions for introgression between Hercules beetles (Dynastes, Dynastinae). AB - The prevalence and consequences of genetic introgression between species have been intensively debated. I used Hercules beetles as examples to test for conditions that may be associated with the occurrence of introgression. RADseq data were used to reconstruct the species tree and history of introgression between Hercules beetles. Image data from museum specimens were used to investigate the phenotypic similarity of two adaptive traits between species from two distinct climatic realms (Nearctic vs. Neotropical). Genetic introgression was identified between Hercules beetles living in geographic proximity (parapatric). Phylogenetic relatedness and phenotypic similarity did not predict nor preclude genetic introgression between species. Phenotypic assimilation in body coloration was evident between distantly related Hercules beetles codistributed in Central America, where directional introgression was also statistically supported from the putative donor to receiver lineages. The number of introgressed loci was significantly higher between species with than without phenotypic similarity. I discuss the implications of recent studies on adaptive genetic introgression by providing supporting evidence from the Hercules beetle system. PMID- 27661064 TI - Iatrogenic facial nerve injuries during chronic otitis media surgery: a multicentre retrospective study. AB - OBJECTIVES: To give an insight into why, when and where iatrogenic facial nerve (FN) injuries may occur and to explain how to deal with them in an emergency setting. DESIGN AND SETTING: Multicentre retrospective study in eight tertiary referral hospitals over 17 years. PARTICIPANTS: Twenty patients with partial or total FN injury during surgery for chronic otitis media (COM) were revised. MAIN OUTCOME MEASURES: Indication and type of surgery, experience of the surgeon, intra- and postoperative findings, value of CT scanning, patient management and final FN outcome were recorded. RESULTS: In 12 cases, the nerve was completely transected, but the surgeon was unaware in 11 cases. A minority of cases occurred in academic teaching hospitals. Tympanic segment, second genu and proximal mastoid segments were the sites involved during injury. The FN was not deliberately identified in 18 patients at the time of injury, and nerve monitoring was only applied in one patient. Before revision surgery, CT scanning correctly identified the lesion site in 11 of 12 cases and depicted additional lesions such as damage to the lateral semicircular canal. A greater auricular nerve graft was interposed in 10 cases of total transection and in one partially lesioned nerve: seven of them resulted in an HB III functional outcome. In two of the transected nerves, rerouting and direct end-to-end anastomosis was applied. A simple FN decompression was used in four cases of superficially traumatised nerves. CONCLUSIONS: We suggest checklists for preoperative, intraoperative and postoperative management to prevent and treat iatrogenic FN injury during COM surgery. PMID- 27661065 TI - High migration rates shape the postglacial history of amphi-Atlantic bryophytes. AB - Paleontological evidence and current patterns of angiosperm species richness suggest that European biota experienced more severe bottlenecks than North American ones during the last glacial maximum. How well this pattern fits other plant species is less clear. Bryophytes offer a unique opportunity to contrast the impact of the last glacial maximum in North America and Europe because about 60% of the European bryoflora is shared with North America. Here, we use population genetic analyses based on approximate Bayesian computation on eight amphi-Atlantic species to test the hypothesis that North American populations were less impacted by the last glacial maximum, exhibiting higher levels of genetic diversity than European ones and ultimately serving as a refugium for the postglacial recolonization of Europe. In contrast with this hypothesis, the best fit demographic model involved similar patterns of population size contractions, comparable levels of genetic diversity and balanced migration rates between European and North American populations. Our results thus suggest that bryophytes have experienced comparable demographic glacial histories on both sides of the Atlantic. Although a weak, but significant genetic structure was systematically recovered between European and North American populations, evidence for migration from and towards both continents suggests that amphi-Atlantic bryophyte population may function as a metapopulation network. Reconstructing the biogeographic history of either North American or European bryophyte populations therefore requires a large, trans-Atlantic geographic framework. PMID- 27661066 TI - Femtosecond-Assisted Big Bubble: A Feasibility Study. AB - PURPOSE: To evaluate the feasibility of femtosecond laser-assisted (FA) tunnel creation as a pretreatment for creating a big bubble (BB) to pneumo-dissect the corneal stroma from Descemet membrane. METHODS: Five human cadaver eyes received pretreatment using a femtosecond laser. An intrastromal tunnel, along with a side cut, was achieved using customized femtosecond corneal disruption (custom mask). Before treatment, optical coherence tomography was performed and the intrastromal tunnel was intended to achieve a parallel orientation with respect to the corneal endothelial cell layer (50 um above the endothelium). Surgical dissection of the side cut using a Sinskey hook was performed, followed by insertion of a deep anterior lamellar keratoplasty cannula into the tunnel and pneumo-dissection (BB). All corneas after treatment were prepared for histologic evaluation (light microscopy). RESULTS: FA pretreatment was successful in all 5 cadaveric corneas, and the BB was achieved in all eyes as well. Histologic evaluation of the corneas revealed complete separation of Descemet membrane and stroma in all eyes, with no remaining stroma attached to Descemet membrane and no signs of perforation. CONCLUSIONS: FABB seems feasible because pneumo-dissection of the corneal stroma from Descemet membrane was achieved in all human cadaver corneas of this experimental study. Optical coherence tomography, corneal histology, and macroscopic evaluation revealed complete Descemet-stromal separation. PMID- 27661067 TI - Combined Use of Rituximab and Intravenous Immunoglobulin for Severe Autoimmune Cicatricial Conjunctivitis-An Interventional Case Series. AB - PURPOSE: Despite the availability of systemic immunosuppressants, cicatricial conjunctivitis (CC) remains a potentially blinding ocular surface disease. We aim to describe the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) for severe recalcitrant autoimmune CC. METHODS: In this single-center retrospective interventional case series with follow-up between 32 and 65 months, 3 cases with mucous membrane pemphigoid (patients 1-3) and 1 case with linear IgA disease (patient 4) were included. Initial conventional immunosuppressive therapy regimens included systemic steroids, dapsone, and mycophenolate. At the time of initiation of RTX and IVIg, all patients had only one eye with good visual acuity or good visual potential. Treatment included 1 to 2 cycles of RTX (1000 mg twice at an interval of 2 weeks apart), and 2 to 9 monthly courses of IVIg (2 g/kg over 3 days). Outcome measures were blindness, as defined by best spectacle-corrected visual acuity <0.05 on a decimal scale, and clinical staging of cicatricial disease (Rowsey and Foster staging). RESULTS: In 4 presented cases, progression of cicatricial disease was stopped as assessed by the Foster grading scale and visual acuity was stabilized in all patients. Conjunctival scarring was stabilized in 2 cases and continued to progress in 2 cases. One patient developed septicemia 6 weeks after RTX infusion, which was successfully treated. CONCLUSIONS: Combination therapy of RTX and IVIg is a potent treatment regimen for recalcitrant autoimmune CC. Further prospective controlled studies on efficacy and safety are warranted before widespread clinical application. PMID- 27661068 TI - Descemet Stripping Automated Endothelial Keratoplasty Outcomes in Patients With Cytomegalovirus Endotheliitis. AB - PURPOSE: There is currently limited information regarding the outcomes of endothelial keratoplasty in eyes with cytomegalovirus (CMV) endotheliitis. We report the results of Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to CMV. METHODS: This is a retrospective review of 4 eyes of 4 patients with CMV endotheliitis and DSAEK. CMV was confirmed in each case by a positive aqueous tap on qualitative polymerase chain reaction. The clinical characteristics of the patients and postoperative outcomes were studied. RESULTS: The mean age of the 4 patients was 69.6 +/- 8.1 years. Two were ethnically Vietnamese, 1 Chinese, and 1 Lebanese. All were immunocompetent. Three eyes had presented with hypertensive uveitis and 1 with bullous keratopathy. Twelve DSAEKs were performed in total in the 4 eyes. Five grafts were performed without any perioperative treatment with oral valganciclovir. All subsequently failed after a mean of 8.0 +/- 3.8 months. Seven grafts were managed with oral valganciclovir; 2 of these grafts failed after 18 and 37 months, and 1 graft had primary graft failure. Four grafts are currently surviving, despite an episode of CMV reactivation in 2 grafts. CONCLUSIONS: In cases of unexplained corneal decompensation or early graft failure after uncomplicated DSAEK, a diagnosis of CMV infection must be considered. Subsequent management of DSAEK in such cases remains challenging. The postoperative course can be complicated by CMV reactivation, which may masquerade either as graft rejection or graft failure. Long-term treatment with oral valganciclovir or topical ganciclovir may be required to decrease graft failure rates. PMID- 27661069 TI - Two-Year Refractive Outcomes After Descemet Membrane Endothelial Keratoplasty. AB - PURPOSE: To monitor refractive changes after Descemet membrane endothelial keratoplasty (DMEK) and to determine what may influence these changes and the time point of stabilization. METHODS: From 67 pseudophakic DMEK eyes operated on for Fuchs endothelial dystrophy at a tertiary referral center, biomicroscopy, visual acuity, subjective refraction, and Scheimpflug-based corneal tomography data were obtained before and up to 2 years postoperatively. Visual acuity and changes in spherical equivalent (SE), mean anterior and posterior simulated keratometry (Km), and central pachymetry were analyzed. RESULTS: At 3 months postoperatively, both hyperopic (28/67 eyes) and myopic (21/67 eyes) shifts were observed; 18/67 eyes showed no SE change. The mean change in SE at 3 months was +0.33 diopters (D) (95% confidence interval = [0.11, 0.54], P = 0.028), which stabilized thereafter (P > 0.466). Initial flattening of mean anterior Km by 0.66D (95% confidence interval = [-0.81, -0.51], P < 0.001) at 3 months was followed by a slow steepening, which became significant between 1 and 2 years postoperatively (P < 0.001). Posterior Km stabilized after 3 months (P > 0.252). Preoperative to 3 months postoperative absolute changes in anterior Km were positively related to preoperative backscattered light from the central anterior cornea (P = 0.035), and the presence of partial graft detachment postoperatively (P = 0.013). CONCLUSIONS: After DMEK, SE and posterior corneal curvature were on average stable at 3 months after surgery, whereas the mean anterior corneal curvature showed an ongoing gradual change. Changes in anterior corneal curvature may be related to preoperative anterior corneal densitometry or postoperative partial graft detachment. PMID- 27661070 TI - Contralateral Autologous Corneal Transplantation Experience in Mexico City. AB - PURPOSE: The aim of this study is to expand the limited knowledge regarding autologous contralateral penetrating keratoplasty. METHODS: We report the retrospective outcomes of patients who received autokeratoplasty and contralateral opaque corneas in the donor eye at a tertiary care ophthalmology hospital in Mexico City. RESULTS: Eleven patients received autokeratoplasty and contralateral opaque corneas in the donor eye at our center from 2010 to 2015. The mean patient age at the time of surgery was 58 years (range, 35-85 yrs), with 4 female and 7 male patients. There were no surgical or immediate postsurgical complications in the autokeratoplasty eye. However, 1 patient had expulsive hemorrhage in the sightless eye. Follow-up duration ranged from 11 to 65 months (mean, 26 mo). During follow-up, 3 of the autokeratoplasty procedures failed because of endothelial attenuation. Identified known risk factors for failure of the eye with visual potential included the presence of an Ahmed glaucoma drainage device in 7/11 patients (63%), history of glaucoma in 8/11 (72%), past heterologous penetrating keratoplasty in 2/11 (18%), Vogt-Koyanagi-Harada syndrome in 1/11 (9%), and 4-quadrant corneal vascularization in 1/11 (9%). CONCLUSIONS: Autokeratoplasty is a good choice in cases having high risk factors and when fresh corneal tissue is not available. This is the largest study describing outcomes of patients who underwent autokeratoplasty. This technique offers no risk of immune rejection and no need for immunosuppression treatment. This study reports a good prognosis in cases having high risk factors for failure. PMID- 27661071 TI - Influence of Ophthalmic Solutions on Tear Components. AB - Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments. PMID- 27661072 TI - Regulatory Mechanism of Collagen Degradation by Keratocytes and Corneal Inflammation: The Role of Urokinase-Type Plasminogen Activator. AB - Keratocytes, corneal resident cells in the corneal stroma, exist between collagen lamellae and maintain the corneal stromal structure. When the corneal stroma is damaged, keratocytes are transformed to myofibroblasts to aid corneal wound healing by phagocytizing debris. Keratocytes and extracellular collagen influence each other because keratocytes cultured in a 3D collagen gel undergo morphological changes and keratocytes produce metalloproteases that degrade extracellular collagen. IL-1 and plasminogen are critical mediators for collagen degradation. The plasminogen system contributes to tissue repair by activating matrix metalloproteinases (MMPs), releasing growth factors from the extracellular matrix and extracellular matrix degradation. Urokinase-type plasminogen activator (uPA) is thought to be involved in corneal disorders and regulates corneal wound healing. uPA is a serine protease synthesized by various cells such as corneal epithelial cells, corneal fibroblasts, vascular endothelial cells, smooth muscle cells, monocytes, macrophages, and malignant tumor cells of different origins. Here, we review the role of uPA in corneal stromal wound healing. uPA is expressed in leukocytes and corneal fibroblasts in the corneas of patients with corneal ulcerations suggesting it is a key regulator of corneal stromal wound healing. uPA is directly involved in plasmin-mediated collagen degradation induced by IL-1. Moreover, uPA is critically involved in promoting leukocyte infiltration in corneal inflammation by activating MMP-9. This activation is presumably directly and indirectly mediated by the plasminogen/plasmin cascade. Moreover, uPA mediates the release of inflammatory cytokines from corneal fibroblasts to promote leukocyte infiltration. PMID- 27661073 TI - Noninvasive Dry Eye Assessment Using High-Technology Ophthalmic Examination Devices. AB - Recently, the number of dry eye cases has dramatically increased. Thus, it is important that easy screening, exact diagnoses, and suitable treatments be available. We developed 3 original and noninvasive assessments for this disorder. First, a DR-1 dry eye monitor was used to determine the tear meniscus height quantitatively by capturing a tear meniscus digital image that was analyzed by Meniscus Processor software. The DR-1 meniscus height value significantly correlated with the fluorescein meniscus height (r = 0.06, Bland-Altman analysis). At a cutoff value of 0.22 mm, sensitivity of the dry eye diagnosis was 84.1% with 90.9% specificity. Second, the Tear Stability Analysis System was used to quantitatively measure tear film stability using a topographic modeling system corneal shape analysis device. Tear film stability was objectively and quantitatively evaluated every second during sustained eye openings. The Tear Stability Analysis System is currently installed in an RT-7000 autorefractometer and topographer to automate the diagnosis of dry eye. Third, the Ocular Surface Thermographer uses ophthalmic thermography for diagnosis. The decrease in ocular surface temperature in dry eyes was significantly greater than that in normal eyes (P < 0.001) at 10 seconds after eye opening. Decreased corneal temperature correlated significantly with the tear film breakup time (r = 0.572; P < 0.001). When changes in the ocular surface temperature of the cornea were used as indicators for dry eye, sensitivity was 0.83 and specificity was 0.80 after 10 seconds. This article describes the details and potential of these 3 noninvasive dry eye assessment systems. PMID- 27661074 TI - Pathogenic Memory Th2 Cells in Airway Inflammation. PMID- 27661075 TI - Exfoliative Cytology in the Diagnosis of Ocular Surface Squamous Neoplasms. AB - PURPOSE: Surface tumors of the eye comprise an ample spectrum of diseases with various clinical manifestations. Diagnosis has been traditionally achieved through core biopsies, but cytology is an innovative, fast, and minimally invasive method. The objective of this study was to investigate the use of exfoliative cytology as an alternative method for the detection of ocular surface squamous neoplasm (OSSN). METHODS: Exfoliative cytology of the lesions was performed by collecting smears using plastic brushes followed by smearing the cells onto slides and subsequently fixing them in 90% alcohol. Incisional biopsies were performed at the exact same location and sent for processing in 10% formaldehyde. Both the surgical pathologist and cytopathologist were masked to the clinical characteristics and to the corresponding cytological or histological result. RESULTS: Twenty-two patients were enrolled in the study (12 men and 10 women, median age 52.5 years). Final histological diagnoses comprised 7 cases of pterygium, 7 squamous-cell carcinomas, 4 squamous papillomas, and 4 chronic inflammatory processes. Cytohistological agreement was achieved in 19 (86.4%) of the samples. Cytology showed a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 86.7%, 75%, and 92.9%, respectively, in detecting OSSN. CONCLUSIONS: Exfoliative cytology of the conjunctival lesions is a simple procedure, with high agreement to the histological follow-up. Its broad use could augment the early diagnosis of OSSN, with improvement in patient prognosis. PMID- 27661076 TI - Improvement of ischemic or congested wound conditions by reconstruction with microsurgical flaps. AB - BACKGROUND: Intractable chronic wounds share the basic problem of the environment being unfavorable for wound healing and prone to infection, inflammation, and recurrences. Microsurgical flap provides a healthy, well-vascularized normal tissue to compromised intractable environment, and promotes wound healing. In this report, we present the results of microsurgical flaps used for the reconstruction of chronic intractable conditions including chronic ulcer with an ischemic environment and pathologic lesions with a congestive environment. PATIENTS AND METHODS: From 1997 to 2015, 18 patients received microsurgical flaps for chronic intractable conditions. Among them, three patients had radiation ulcers with an ischemic environment and 15 had pathologic lesions with a congested environment, such as vascular malformations. Nine patients were male, and nine were female. The mean age was 31.9 years. All patients were treated using radical excision and reconstruction with microsurgical tissue transfer. RESULTS: All flaps survived completely. Among three patients with radiation ulcers, two had minor wound disruptions, which were managed conservatively. No further episodes of infections or breakdowns occurred. Among 15 patients who had pathologic lesions, one suffered facial palsy of the forehead. No complications in terms of infection, or recurrences were noted, and resolution of the residual surrounding lesions was observed on follow-ups. No donor related problems occurred in any patients. The mean follow-up period was 10.7 years. CONCLUSION: In this report, we present the results of reconstruction of chronic intractable conditions using microsurgical flaps. The reconstruction using microsurgical flaps was clinically successful, with long-term improvement of surrounding tissues and no recurrence. PMID- 27661077 TI - Genomic divergence and lack of introgressive hybridization between two 13-year periodical cicadas support life cycle switching in the face of climate change. AB - Life history evolution spurred by post-Pleistocene climatic change is hypothesized to be responsible for the present diversity in periodical cicadas (Magicicada), but the mechanism of life cycle change has been controversial. To understand the divergence process of 13-year and 17-year cicada life cycles, we studied genetic relationships between two synchronously emerging, parapatric 13 year periodical cicada species in the Decim group, Magicicada tredecim and M. neotredecim. The latter was hypothesized to be of hybrid origin or to have switched from a 17-year cycle via developmental plasticity. Phylogenetic analysis using restriction-site-associated DNA sequences for all Decim species and broods revealed that the 13-year M. tredecim lineage is genomically distinct from 17 year Magicicada septendecim but that 13-year M. neotredecim is not. We detected no significant introgression between M. tredecim and M. neotredecim/M. septendecim thus refuting the hypothesis that M. neotredecim are products of hybridization between M. tredecim and M. septendecim. Further, we found that introgressive hybridization is very rare or absent in the contact zone between the two 13-year species evidenced by segregation patterns in single nucleotide polymorphisms, mitochondrial lineage identity and head width and abdominal sternite colour phenotypes. Our study demonstrates that the two 13-year Decim species are of independent origin and nearly completely reproductively isolated. Combining our data with increasing observations of occasional life cycle change in part of a cohort (e.g. 4-year acceleration of emergence in 17-year species), we suggest a pivotal role for developmental plasticity in Magicicada life cycle evolution. PMID- 27661078 TI - Experimental Evolution of Gene Expression and Plasticity in Alternative Selective Regimes. AB - Little is known of how gene expression and its plasticity evolves as populations adapt to different environmental regimes. Expression is expected to evolve adaptively in all populations but only those populations experiencing environmental heterogeneity are expected to show adaptive evolution of plasticity. We measured the transcriptome in a cadmium-enriched diet and a salt enriched diet for experimental populations of Drosophila melanogaster that evolved for ~130 generations in one of four selective regimes: two constant regimes maintained in either cadmium or salt diets and two heterogeneous regimes that varied either temporally or spatially between the two diets. For populations evolving in constant regimes, we find a strong signature of counter-gradient evolution; the evolved expression differences between populations adapted to alternative diets is opposite to the plastic response of the ancestral population that is naive to both diets. Based on expression patterns in the ancestral populations, we identify a set of genes for which we predict selection in heterogeneous regimes to result in increases in plasticity and we find the expected pattern. In contrast, a set of genes where we predicted reduced plasticity did not follow expectation. Nonetheless, both gene sets showed a pattern consistent with adaptive expression evolution in heterogeneous regimes, highlighting the difference between observing "optimal" plasticity and improvements in environment-specific expression. Looking across all genes, there is evidence in all regimes of differences in biased allele expression across environments ("allelic plasticity") and this is more common among genes with plasticity in total expression. PMID- 27661080 TI - Intensity of Mutualism Breakdown Is Determined by Temperature Not Amplification of Wolbachia Genes. AB - Wolbachia are maternally transmitted intracellular bacterial symbionts that infect approximately 40% of all insect species. Though several strains of Wolbachia naturally infect Drosophila melanogaster and provide resistance against viral pathogens, or provision metabolites during periods of nutritional stress, one virulent strain, wMelPop, reduces fly lifespan by half, possibly as a consequence of over-replication. While the mechanisms that allow wMelPop to over replicate are still of debate, a unique tandem repeat locus in the wMelPop genome that contains eight genes, referred to as the "Octomom" locus has been identified and is thought to play an important regulatory role. Estimates of Octomom locus copy number correlated increasing copy number to both Wolbachia bacterial density and increased pathology. Here we demonstrate that infected fly pathology is not dependent on an increased Octomom copy number, but does strongly correlate with increasing temperature. When measured across developmental time, we also show Octomom copy number to be highly variable across developmental time within a single generation. Using a second pathogenic strain of Wolbachia, we further demonstrate reduced insect lifespan can occur independently of a high Octomom locus copy number. Taken together, this data demonstrates that the mechanism/s of wMelPop virulence is more complex than has been previously described. PMID- 27661079 TI - Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients. AB - The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain specific miRNAs, in acute ischemic stroke (AIS) patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01). The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications. PMID- 27661081 TI - Decreased Sperm Motility Retarded ICSI Fertilization Rate in Severe Oligozoospermia but Good-Quality Embryo Transfer Had Achieved the Prospective Clinical Outcomes. AB - INTRODUCTION: Spermatozoa motility is the critical parameter to affect the treatment outcomes during assisted reproductive technologies (ART), but its reproductive capability remains a little informed in condition of severe male factor infertility. This retrospective cohort study aimed to evaluate the effects of reduced sperm motility on the embryological and clinical outcomes in intra cytoplasmic sperm injection (ICSI) treatment of severe oligozoospermia. PATIENTS AND METHODS: 966 cycles (812 couples) of severe oligozoospermia diagnosed by spermatozoa count <= 5 * 106/mL and motile spermatozoa <= 2 * 106/mL were divided into four groups in according to the number of motile spermatozoa in one ejaculate on the day of oocyte retrieval (Group B-E). The control (Group A) was 188 cycles of moderate oligozoospermia with spermatozoa count > 5 * 106/mL and motile spermatozoa > 2 * 106/mL. All female partners were younger than 35 years of age. Logistic regression analyzed embryological outcomes (the rates of fertilization, cleavage and good-quality embryo) and clinical outcomes (the rates of pregnancy, implantation, early miscarriage and live birth). Quality of embryo transfer (ET) was divided into three classes as continuous factor to test the effects of embryo quality on clinical outcomes. RESULTS: The reduction in the number of motile sperm in four groups of severe oligozoospermia gave rise to comparable inability of the fertilization (p < 0.001) and a decreased rate of good-quality embryo at Day 3 (p < 0.001) by compared to the control. The cleavage rate of the derived zygotes was similar to the control. ET classes significantly affected the clinical outcomes (p < 0.001). Class I ET gave rise to similar rates of clinical outcomes between five groups, but Class II and Class III ET retarded the rates of pregnancy, implantation and live birth and this particularly occurred in Group C, D and E. The rate of early miscarriage was not comparably different between groups. Overall rates in all groups were 41.26% clinical pregnancy, 25.74% implantation and 36.32% live birth, which gave live birth to 252 girls and 252 boys. CONCLUSIONS: The reduction of motile spermatozoa in severe oligozoospermia decreased the rates of fertilization and good-quality embryo. Obtaining and transfer of good-quality embryos was the good prognostic to achieve prospective clinical outcomes regardless of the severity of oligozoospermia. PMID- 27661083 TI - Agreement between Computerized and Human Assessment of Performance on the Ruff Figural Fluency Test. AB - The Ruff Figural Fluency Test (RFFT) is a sensitive test for nonverbal fluency suitable for all age groups. However, assessment of performance on the RFFT is time-consuming and may be affected by interrater differences. Therefore, we developed computer software specifically designed to analyze performance on the RFFT by automated pattern recognition. The aim of this study was to compare assessment by the new software with conventional assessment by human raters. The software was developed using data from the Lifelines Cohort Study and validated in an independent cohort of the Prevention of Renal and Vascular End Stage Disease (PREVEND) study. The total study population included 1,761 persons: 54% men; mean age (SD), 58 (10) years. All RFFT protocols were assessed by the new software and two independent human raters (criterion standard). The mean number of unique designs (SD) was 81 (29) and the median number of perseverative errors (interquartile range) was 9 (4 to 16). The intraclass correlation coefficient (ICC) between the computerized and human assessment was 0.994 (95%CI, 0.988 to 0.996; p<0.001) and 0.991 (95%CI, 0.990 to 0.991; p<0.001) for the number of unique designs and perseverative errors, respectively. The mean difference (SD) between the computerized and human assessment was -1.42 (2.78) and +0.02 (1.94) points for the number of unique designs and perseverative errors, respectively. This was comparable to the agreement between two independent human assessments: ICC, 0.995 (0.994 to 0.995; p<0.001) and 0.985 (0.982 to 0.988; p<0.001), and mean difference (SD), -0.44 (2.98) and +0.56 (2.36) points for the number of unique designs and perseverative errors, respectively. We conclude that the agreement between the computerized and human assessment was very high and comparable to the agreement between two independent human assessments. Therefore, the software is an accurate tool for the assessment of performance on the RFFT. PMID- 27661082 TI - 640-Slice CT Measurement of Superior Orbital Fissure as Gateway for Light into the Brain: Statistical Evaluation of Area and Distance. AB - OBJECTIVE: Our aim was to provide normative data concerning superior orbital fissure area (SOFA), ocular skin and the substantia nigra (D-SS) and orbital fissure and the substantia nigra (D-SOF-S) distances by CT scan in adult Caucasian population. METHODS: The area of the superior orbital fissure (SOF), the distance between the ocular skin and the substantia nigra and the distance between the superior orbital fissure and the substantia nigra using CT and 3D-CT images. RESULTS: Normative data stratified for age and gender were obtained. The data here reported show that some degree of variability in SOFA, D-SS and D-SOF-S measurements can be observed healthy Caucasian subjects. Gender stratified prediction intervals (mean +/- 2 Standard Deviations) for SOFA and D-SOF-S were 69.2 (+/-15.8) and 38.4 (+/-7.6) for male and 56.8 (+/-11.9) and 36.5 (+/-6.1) for female, respectively. Age and gender significantly impacted on D-SS values and normative data were constructed generating data stratified for these two variables. D-SS was 89.4 (+/-10.3) and 86.4 (+/-9.7) for male and female, respectively. CONCLUSIONS: Here we provide adjunctive anatomical information on specific anatomical cerebral zones. Our data may have implications for surgeons actively committed to treat pathological conditions involving these cerebral areas. Additionally, the anatomical variability found with respect to SOF and the potential different exposure of the substanzia nigra to the bright light could play a role in Parkinson's disease as already speculated in literature. PMID- 27661084 TI - Simultaneous Quantification of Anticardiolipin IgG and IgM by Time Resolved Fluoroimmunoassay. AB - The autoimmune disease antiphospholipid syndrome (APS) is characterized by the presence of anticardiolipin antibodies (aCL), along with anti-beta2-glycoprotein I (beta2GPI) antibodies and lupus anticoagulant (LA). In this study, we developed a time-resolved fluoroimmunoassay (TRFIA) system for simultaneous quantification of aCL IgG and IgM. A 96-well microtiter plate precoated with the complex of cardiolipin from bovine heart and bovine beta2GPI was incubated with the anticardiolipin IgG and IgM standard substance or serum, and the conjugate of Eu3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM was pipetted to the wells to form a tipical double-antibody-sandwich immunoreactions; finally the fluorescent intensity of Eu3+ and Sm3+ was detected to reflect the quantity of anticardiolipin IgG and IgM. This assay showed a good relationship between fluorescence intensities and the concentration of anticardiolipin antibody(aCL) IgG and IgM, with a low-end sensitivity of 0.1 U/ml for IgG and 0.1 U/ml for IgM, respectively. The intra- and inter-assay coefficients of variation (CV) of the calibrators was 3.0% and 4.51% for IgG, and 2.76% and 4.45% for IgM. The average recovery was 100.38% for aCL IgG and 100.45% for aCL IgM. For serum samples, the results of our method showed a good correlation with those obtained with ELISA kit. Simultaneous detection of aCL-IgG and aCL-IgM in the same reaction well can optimize assay performance by avoiding potential influence of different reaction conditions-timing, and well-to-well difference in concentration and characteristics of cardiolipin antigen. The results of a combo aCL-IgG and aCL IgM assay for the same sample are more consistent and more reliable. This dual label time-resolved fluoroimmunoassay is sensitive for detecting aCL IgG and IgM across a wide concentration range with stable reagents and may assist in the clinical diagnosis of antiphospholipid syndrome. PMID- 27661085 TI - Binding and Inhibition of Spermidine Synthase from Plasmodium falciparum and Implications for In Vitro Inhibitor Testing. AB - The aminopropyltransferase spermidine synthase (SpdS) is a promising drug target in cancer and in protozoan diseases including malaria. Plasmodium falciparum SpdS (PfSpdS) transfers the aminopropyl group of decarboxylated S-adenosylmethionine (dcAdoMet) to putrescine or to spermidine to form spermidine or spermine, respectively. In an effort to understand why efficient inhibitors of PfSpdS have been elusive, the present study uses enzyme activity assays and isothermal titration calorimetry with verified or predicted inhibitors of PfSpdS to analyze the relationship between binding affinity as assessed by KD and inhibitory activity as assessed by IC50. The results show that some predicted inhibitors bind to the enzyme with high affinity but are poor inhibitors. Binding studies with PfSpdS substrates and products strongly support an ordered sequential mechanism in which the aminopropyl donor (dcAdoMet) site must be occupied before the aminopropyl acceptor (putrescine) site can be occupied. Analysis of the results also shows that the ordered sequential mechanism adequately accounts for the complex relationship between IC50 and KD and may explain the limited success of previous efforts at structure-based inhibitor design for PfSpdS. Based on PfSpdS active-site occupancy, we suggest a classification of ligands that can help to predict the KD-IC50 relations in future design of new inhibitors. The present findings may be relevant for other drug targets that follow an ordered sequential mechanism. PMID- 27661087 TI - Magnetic Field Landscapes Guiding the Chemisorption of Diamagnetic Molecules. AB - It is shown that the self-assembly of diamagnetic molecule submonolayers on a surface can be influenced by magnetic stray field landscapes emerging from artificially fabricated magnetic domains and domain walls. The directed local chemisorption of diamagnetic subphthalocyaninatoboron molecules in relation to the artificially created domain pattern is proved by a combination of surface analytical methods: ToF-SIMS, X-PEEM, and NEXAFS imaging. Thereby, a new method to influence self-assembly processes and to produce patterned submonolayers is presented. PMID- 27661086 TI - The Salinity Responsive Mechanism of a Hydroxyproline-Tolerant Mutant of Peanut Based on Digital Gene Expression Profiling Analysis. AB - Soil salinity seriously limits plant growth and yield. Strategies have been developed for plants to cope with various environmental stresses during evolution. To screen for the broad-spectrum genes and the molecular mechanism about a hydroxyproline-tolerant mutant of peanut with enhanced salinity resistance under salinity stress, digital gene expression (DGE) sequencing was performed in the leaves of salinity-resistant mutant (S2) and Huayu20 as control (S4) under salt stress. The results indicate that major transcription factor families linked to salinity stress responses (NAC, bHLH, WRKY, AP2/ERF) are differentially expressed in the leaves of peanut under salinity stress. In addition, genes related to cell wall loosening and stiffening (xyloglucan endotransglucosylase/hydrolases, peroxidases, lipid transfer protein, expansin, extension), late embryogenesis abundant protein family, fatty acid biosynthesis and metabolism (13-lipoxygenase omega-6 fatty acid desaturase, omega-3 fatty acid desaturase) and some previously reported stress-related genes encoding proteins such as defensin, universal stress protein, metallothionein, peroxidase etc, and some other known or unknown function stress related genes, have been identified. The information from this study will be useful for further research on the mechanism of salinity resistance and will provide a useful genomic resource for the breeding of salinity resistance variety in peanut. PMID- 27661089 TI - Spectral Hole Burning in Cyanobacterial Photosystem I with P700 in Oxidized and Neutral States. AB - We explored the rich satellite hole structures emerging as a result of spectral hole burning in cyanobacterial photosystem I (PSI) and demonstrated that hole burning properties of PSI, particularly at high resolution, are strongly affected by the oxidation state of the primary donor P700, as P700+ effectively quenches the excitations of the lowest-energy antenna states responsible for fluorescence. Obtaining better control of this variable will be crucial for high-resolution ensemble experiments on protein energy landscapes in PSI. The separate nonphotochemical spectral hole burning (NPHB) signatures of various red antenna states were obtained, allowing for additional constraints on excitonic structure based calculations. Preliminary evidence is presented for an additional red state of PSI of T. elongatus peaked at 712.6 nm, distinct from previously reported C708 and C715 states and possibly involving chlorophyll B15. Excitation at wavelengths as long as 800 nm results in charge separation at cryogenic temperatures in PSI also in Synechocystis sp. PCC 6803. Both the "P700+ minus P700" holes and nonphotochemical spectral holes were subjected to thermocycling. The distribution of barriers manifesting in recovery of the "P700+ minus P700" signature contains two components in sample-dependent proportions, likely reflecting the percentages of FA and FB clusters being successfully prereduced before the optical experiment. The barrier distribution for the recovery of the lower-energy nonphotochemical spectral holes resembles those observed for other pigment protein complexes, suggesting similar structural elements are responsible for NPHB. Higher-energy components exhibit evidence of "domino effects" such as shifts of certain bands persisting past the lower-energy hole recovery. Thus, conformational changes triggered by excitation of one pigment likely can affect multiple pigments in this tightly packed system. PMID- 27661088 TI - Effects of Ultraviolet (UV) on Degradation of Irgafos 168 and Migration of Its Degradation Products from Polypropylene Films. AB - The effects of ultraviolet (UV) irradiation on the degradation of Irgafos 168 and the migration of its two degradation products, 2,4-di-tert-butylphenol and tris(2,4-di-tert-butylphenyl)phosphate, from polypropylene (PP) were investigated. A blown film machine was used to extrude PP films containing Irgafos 168, the films were stored in the dark for 45 days, two UV treatments and sunlight exposure were applied to the films, and GC-MS was used for degradation and migration studies. Extrusion, storage, UV treatments, and sunlight exposure significantly affected concentrations of Irgafos 168 and the degradation products. 2,4-Di-tert-butylphenol was the major degradation product produced by UV irradiation, but tris(2,4-di-tert-butylphenyl)phosphate was the major degradation product produced by extrusion, storage, and sunlight exposure. The degradation products have no or little health risk, because migration study and threshold of toxicological concern (TTC) analysis show that experimental maximum migration of 2,4-di-tert-butylphenol and tris(2,4-di-tert-butylphenyl)phosphate are only 2 and 53% of the theoretical maximum migration amounts, respectively. PMID- 27661090 TI - Structural Analysis of Natural Products. AB - Current mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray diffraction are presented as structure elucidation tools for analytical chemistry of natural products. Discovering new molecular entities combined with dereplication of known organic compounds represent prerequisites for biological assays and for respective applications as pharmaceuticals or molecular markers. Liquid chromatography is briefly addressed with respect to its use in mass spectrometry- and nuclear magnetic resonance-based metabolomics studies. PMID- 27661091 TI - Prototropic MU-H8,9 and MU-H9,10 Tautomers Derived from the [nido-5,6-C2B8H11]- Anion. AB - Reported is an unusual tautomeric behavior within the [nido-5,6-C2B8H11]- (1a-) cage that has no precedence in the whole area of carborane chemistry. Isolated were two skeletal tautomers, anions [6-Ph-nido-5,6-C2B8H10-MU8,9]- (2d-) and [5,6 Me2-nido-5,6-C2B8H9-MU9,10]- (3b-), which differ in the positioning of the open face hydrogen bridge. Their structures have been determined by X-ray diffraction analyses. The 3b-structure is stabilized by intermolecular interaction involving Et3NH+ and B8-B9 and H8 atoms in the solid phase; however, its dissolution in CD3CN causes instant conversion to the more stable [5,6-Me2-nido-5,6-C2B8H9 MU8,9]- (2b-) tautomer. The dynamic electron-correlation-based MP2/6-31G* computations suggest that the parent [nido-5,6-C2B8H11-MU8,9]- (2a-) tautomer is 3.9 kcal.mol-1 more stable than the [nido-5,6-C2B8H11-MU9,10]- (3a-) counterpart and the MU8,9 structure 2- is therefore the most stable tautomeric form in the solution, as was also demonstrated by multinuclear (1H, 11B, and 13C) NMR measurements on the whole series of C-substituted compounds. PMID- 27661092 TI - Expanding the Scope of the Gold(I)-Catalyzed Rautenstrauch Rearrangement: Protic Additives. AB - The synthesis of substituted 2-cyclopentenones using a commercially available gold(I) catalyst is described under flexible reaction conditions. During the course of our investigations, we discovered that using a proton source as an additive is required to obtain the desired substituted cyclopentenones in good yields. PMID- 27661093 TI - Tailoring Water-Resistant and Breathable Performance of Polyacrylonitrile Nanofibrous Membranes Modified by Polydimethylsiloxane. AB - The demand of water-resistant and breathable materials applied to a separation medium and protective garments is steadily increasing. Typical approaches to obtain these functional materials are based on hydrophobic agents and porous substrates with small fiber diameter, tiny pore, and high porosity. However, a fluorinated hydrophobic finishing agent usually employed in providing effective waterproofness is limited with respect to their environmental persistence and toxic potential. Herein, with the aim to keep a balance between the water resistance and breathability as well as mechanical properties, we fabricate a novel fluoride-free functional membrane by electrospun polyacrylonitrile (PAN) nanofibers modified with polydimethylsiloxane (PDMS). As determined by morphological, DSC, and FT-IR analyses, the curing reaction of PDMS macromolecules formed an abundance of hydrophobic adhesive structures, which improved the waterproof performance dramatically and imparted relative good breathability at the same time. By systematically tuning the curing temperature as well as the concentration of PDMS, the modified PAN membranes with 4 wt % PDMS possessed good water-resistance (80.9 kPa), modest vapor permeability (12.5 kg m 2 d-1), and air permeability (9.9 mm s-1). Compared with pristine PAN membranes, the modified membranes were endowed with enhanced tensile stress of 15.7 MPa. The good comprehensive performance of the as-prepared membranes suggested their potential applications in protective clothing, membrane distillation, self cleaning materials, and other medical products. Furthermore, the proposed relationship between porous structure and waterproof/breathable property as one considerable principle is applicable to designing functional membranes with different levels of protective and comfortable performance. PMID- 27661095 TI - Difluoroalkylation/C-H Annulation Cascade Reaction Induced by Visible-Light Photoredox Catalysis. AB - We report the first example of difluoroalkylation/C-H annulation cascade reactions of cyclopropyl olefins induced by visible-light photoredox catalysis regioselectively affording partially hydrogenated naphthalenes and quinolines with a variety of difluorinated side chains. The alkylation reagent could be extended to monofluoro and trifluoro reagents, nitrile and malonate. The regioselectivity was investigated by means of density functional theory calculations. PMID- 27661094 TI - Free Energy Landscape of GAGA and UUCG RNA Tetraloops. AB - We report the folding thermodynamics of ccUUCGgg and ccGAGAgg RNA tetraloops using atomistic molecular dynamics simulations. We obtain a previously unreported estimation of the folding free energy using parallel tempering in combination with well-tempered metadynamics. A key ingredient is the use of a recently developed metric distance, eRMSD, as a biased collective variable. We find that the native fold of both tetraloops is not the global free energy minimum using the AmberchiOL3 force field. The estimated folding free energies are 30.2 +/- 0.5 kJ/mol for UUCG and 7.5 +/- 0.6 kJ/mol for GAGA, in striking disagreement with experimental data. We evaluate the viability of all possible one-dimensional backbone force field corrections. We find that disfavoring the gauche+ region of alpha and zeta angles consistently improves the existing force field. The level of accuracy achieved with these corrections, however, cannot be considered sufficient by judging on the basis of available thermodynamic data and solution experiments. PMID- 27661096 TI - Large-Scale Production of V6O13 Cathode Materials Assisted by Thermal Gravimetric Analysis-Infrared Spectroscopy Technology. AB - The kilogram-scale fabrication of V6O13 cathode materials has been notably assisted by in situ thermal gravimetric analysis (TGA)-infrared spectroscopy (IR) technology. This technology successfully identified a residue of ammonium metavanadate in commercial V6O13, which is consistent with the X-ray photoelectron spectroscopy result. Samples of V6O13 materials have been fabricated and characterized by TGA-IR, scanning electron microscopy, and X-ray diffraction. The initial testing results at 125 degrees C have shown that test cells containing the sample prepared at 500 degrees C show up to a 10% increase in the initial specific capacity in comparison with commercial V6O13. PMID- 27661098 TI - Immune Cells in Cardiovascular Disease: Has the Time Arrived for New Targets in Human Hypertension? PMID- 27661097 TI - Blood Pressure and Mortality in Long-Term Hemodialysis-Time to Move Forward. AB - Contrary to the direct, graded, and causal relationship of hypertension with cardiovascular outcomes in the general population, among dialysis patients, blood pressure (BP) recorded either predialysis or postdialysis displays a U-shaped curve with mortality. This paradoxical phenomenon of lower BP or a decline in BP over time being associated with increased mortality and higher BP being associated with a lower mortality is described as "reverse" epidemiology of hypertension, raising substantial controversy on whether BP lowering causes harms or benefits among dialysis patients. Unlike the inverse relationship of peridialytic BP with mortality, elevated BP recorded outside of dialysis is directly associated with poor long-term outcomes. Apart from the timing and technique of BP measurement, the U-shaped association of BP with mortality is also modified when accounting for factors related to patient's clinical characteristics and level of illness, dialysis practices, and patterns as well as factors related to the methodology of survival analysis. Most importantly, deliberate BP lowering with antihypertensive drugs is associated with reduced cardiovascular morbidity and mortality. In this review, we explore the complex association of peridialytic, intradialytic, and interdialytic BP with outcomes among dialysis patients. We conclude with recommendations for a wider use of out of-dialysis BP monitoring as a tool to better evaluate the cardiovascular risk and optimize the management of hypertension in this high-risk population. Rather than more cohort studies, we call for randomized trials to test the level of BP in dialysis patients that is optimal for cardiovascular outcomes. PMID- 27661099 TI - An Enumerative Combinatorics Model for Fragmentation Patterns in RNA Sequencing Provides Insights into Nonuniformity of the Expected Fragment Starting-Point and Coverage Profile. AB - RNA sequencing (RNA-seq) has emerged as the method of choice for measuring the expression of RNAs in a given cell population. In most RNA-seq technologies, sequencing the full length of RNA molecules requires fragmentation into smaller pieces. Unfortunately, the issue of nonuniform sequencing coverage across a genomic feature has been a concern in RNA-seq and is attributed to biases for certain fragments in RNA-seq library preparation and sequencing. To investigate the expected coverage obtained from fragmentation, we develop a simple fragmentation model that is independent of bias from the experimental method and is not specific to the transcript sequence. Essentially, we enumerate all configurations for maximal placement of a given fragment length, F, on transcript length, T, to represent every possible fragmentation pattern, from which we compute the expected coverage profile across a transcript. We extend this model to incorporate general empirical attributes such as read length, fragment length distribution, and number of molecules of the transcript. We further introduce the fragment starting-point, fragment coverage, and read coverage profiles. We find that the expected profiles are not uniform and that factors such as fragment length to transcript length ratio, read length to fragment length ratio, fragment length distribution, and number of molecules influence the variability of coverage across a transcript. Finally, we explore a potential application of the model where, with simulations, we show that it is possible to correctly estimate the transcript copy number for any transcript in the RNA-seq experiment. PMID- 27661100 TI - Safety of direct antiviral agents in the management of hepatitis C. AB - INTRODUCTION: Hepatitis C virus is a hepatotropic virus that generally leads to chronic hepatitis and various harmful sequelae. The lone standard of treatment has been pegylated interferon and ribavirin, which produces a modest response and many side effects. However, a new era of management was declared with the introduction of various directly acting antiviral agents. Areas covered: Recent direct antiviral agents (DAAs) primarily target the non-structural proteins of the virus and affect its replication. These agents successfully achieve a sustained virologic response. However, some serious side effects were reported, which may or may not be drug-related effects. Important drug-drug interactions were also reported. The treating physician should be reasonably familiar with these effects. We review the safety profile of these agents in the management of HCV. Expert opinion: Cautious concomitant drug intake is necessary for the new HCV therapies. Future HCV management will depend on interferon-free and likely ribavirin-free regimens. The co-administration of direct antiviral agents of different classes increases the probability of side effects and drug-drug interactions. PMID- 27661101 TI - The new EU regulation on in vitro diagnostics: potential issues at the interface of medicines and companion diagnostics. AB - The new European regulation for in vitro diagnostics (IVD) divides the certification of IVD including companion diagnostics (CDx) by notified bodies (NB) from the market authorization of medicines. With the new regulation, CDx will require conformity assessment which is expected to include clinical evidence by NB. This is a significant change from the current situation: until now most IVD have been certified based on their manufacturers' assessment. For one medicine assessed by the EMA, certification of several different CDx by different NB is possible. As the benefit-risk balance of the medicine may depend on the performance (e.g., sensitivity and specificity) of its CDx, a close cooperation of EMA and NB will be necessary. The availability of detailed information on CDx used in the pivotal clinical trials for the medicine's authorization will become crucial for the assessment of alternative or competing CDx. PMID- 27661103 TI - c-Cbl mediates the degradation of tumorigenic nuclear beta-catenin contributing to the heterogeneity in Wnt activity in colorectal tumors. AB - Despite the loss of Adenomatous Polyposis Coli (APC) in a majority of colorectal cancers (CRC), not all CRCs bear hallmarks of Wnt activation, such as nuclear beta-catenin. This underscores the presence of other Wnt regulators that are important to define, given the pathogenic and prognostic roles of nuclear beta catenin in human CRC. Herein, we investigated the effect of Casitas B-lineage lymphoma (c-Cbl) on nuclear beta-catenin, which is an oncoprotein upregulated in CRC due to loss-of-function APC or gain-of-function CTNNB1 mutations. Despite mechanistic rationale and recent discoveries of c-Cbl's mutations in solid tumors, little is known about its functional importance in CRC. Our study in a cohort of human CRC patients demonstrated an inverse correlation between nuclear beta-catenin and c-Cbl. Further investigation showed that the loss of c-Cbl activity significantly enhanced nuclear beta-catenin and CRC tumor growth in cell culture and a mouse xenograft model. c-Cbl interacted with and downregulated beta catenin in a manner that was independent of CTNNB1 or APC mutation status. This study demonstrates a previously unrecognized function of c-Cbl as a negative regulator of CRC. PMID- 27661102 TI - Similarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer. AB - The tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment. PMID- 27661104 TI - beta-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation. AB - beta-Hydroxybutyrate, a ketone body that is used as an energy source in organs such as the brain, muscle, and heart when blood glucose is low, is produced by fatty acid oxidation in the liver under the fasting state. Endoplasmic reticulum (ER) stress is linked with the generation of intracellular reactive oxygen species and the accumulation of misfolded protein in the ER. ER stress is known to induce the NOD-like receptor protein 3 inflammasome, which mediates activation of the proinflammatory cytokine interleukin-1beta, whose maturation is caspase-1 dependent. We investigated whether beta-hydroxybutyrate modulates ER stress, inflammasome formation, and insulin signaling. Sprague Dawley rats (6 and 24 months of age) that were starved for 3 d and rats treated with beta hydroxybutyrate (200 mg.kg-1.d-1 i.p., for 5 d) were used for in vivo investigations, whereas human hepatoma HepG2 cells were used for in vitro studies. Overexpression of AMPK in cultured cells was performed to elucidate the molecular mechanism. The starvation resulted in increased serum beta hydroxybutyrate levels with decreased ER stress (PERK, IRE1, and ATF6alpha) and inflammasome (ASC, caspase-1, and NLRP3) formation compared with non-fasted 24 month-old rats. In addition, beta-hydroxybutyrate suppressed the increase of ER stress- and inflammasome-related marker proteins. Furthermore, beta hydroxybutyrate treatment increased the expression of manganese superoxide dismutase and catalase via the AMP-activated protein kinase-forkhead box protein O3alpha transcription factor pathway both in vivo and in vitro. The significance of the current study was the discovery of the potential therapeutic role of beta hydroxybutyrate in suppressing ER-stress-induced inflammasome formation. PMID- 27661105 TI - Eosinophil percentage elevation as a prognostic factor for overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor. AB - BACKGROUND: We tried to investigate the prognostic significance of post-treatment eosinophil percentage(Eo %) in metastatic renal cell carcinoma(mRCC) patients undertaking sorafenib. RESULTS: The median OS for the entire sorafenib treatment period was 21.9 months (95% CI: 17.2-25.9 months). Of the 282 mRCC patients, 101 patients experienced an elevated post-treatment Eo % within two months. Median OS of post-treatment Eo % elevated group and non-elevated group were 42.9 months and 16.8 months(p=0.000). After adding post-treatment Eo % into a modified MSKCC model or Heng's model, 43 and 41 patients were reclassified into favorable group, 5 and 9 patients were reclassified to intermediate group respectively. METHODS: mRCC patients treated with sorafenib from 2006 to 2015 in were evaluated. Pre- and post-treatment Eo % were assessed. Oncologic outcomes were analyzed by overall survival and tumor response rate. Predictive parameters were assessed in a Cox proportional hazard model. CONCLUSIONS: Our study demonstrates that an early elevation of Eo % after sorafenib treatment is a strong predictor of good prognosis. Eo % can be a good supplementary for prognostic models using pre treatment parameters. PMID- 27661106 TI - TWIST1/miR-584/TUSC2 pathway induces resistance to apoptosis in thyroid cancer cells. AB - TWIST1, a transcription factor, plays a pivotal role in cancer initiation and progression. Anaplastic thyroid carcinoma (ATC) is one of the deadliest human malignancies; TWIST1 is overexpressed in ATC and increases thyroid cancer cell survival, migration and invasion. The molecular mechanisms underlying the effects of TWIST1 are partially known. Here, using miRNome profiling of papillary thyroid cancer cells (TPC-1) ectopically expressing TWIST1, we identified miR-584. We showed that TWIST1 directly binds miR-584 using chromatin immunoprecipitation. Importantly, miR-584 was up-regulated in human ATC compared to papillary thyroid carcinoma (PTC) and normal thyroid samples. Overexpression of miR-584 in TPC cells induced resistance to apoptosis, whereas stable transfection of anti-miR 584 in TPC-TWIST1 and 8505C cells increased the sensitivity to apoptosis. Using bioinformatics programs, we identified TUSC2 (tumor suppressor candidate 2) as a novel target of miR-584. TUSC2 mRNA and protein levels were decreased in TPC miR 584 and increased in TPC-TWIST1 anti-miR-584 cells. Luciferase assays demonstrated direct targeting. Restored expression of TUSC2 rescued the inhibition of apoptosis induced by miR-584. Finally, qRT-PCR and immunohistochemical analysis showed that TUSC2 was down-regulated in ATC and PTC samples compared to normal thyroids. In conclusion, our study identified a novel TWIST1/miR-584/TUSC2 pathway that plays a role in resistance to apoptosis of thyroid cancer cells. PMID- 27661107 TI - RNF43 and ZNRF3 are commonly altered in serrated pathway colorectal tumorigenesis. AB - Serrated pathway colorectal cancers (CRCs) are characterised by a BRAF mutation and half display microsatellite instability (MSI). The Wnt pathway is commonly upregulated in conventional CRC through APC mutation. By contrast, serrated cancers do not mutate APC. We investigated mutation of the ubiquitin ligases RNF43 and ZNRF3 as alternate mechanism of altering the Wnt signal in serrated colorectal neoplasia. RNF43 was mutated in 47/54(87%) BRAF mutant/MSI and 8/33(24%) BRAF mutant/microsatellite stable cancers compared to only 3/79(4%) BRAF wildtype cancers (p<0.0001). ZNRF3 was mutated in 16/54(30%) BRAF mutant/MSI and 5/33(15%) BRAF mutant/microsatellite stable compared to 0/27 BRAF wild type cancers (p=0.004). An RNF43 frameshift mutation (X659fs) occurred in 80% BRAF mutant/MSI cancers. This high rate was verified in a second series of 25/35(71%) BRAF mutant/MSI cancers. RNF43 and ZNRF3 had lower transcript expression in BRAF mutant compared to BRAF wildtype cancers and less cytoplasmic protein expression in BRAF mutant/MSI compared to other subtypes. Treatment with a porcupine inhibitor reduced RNF43/ZNRF3 mutant colony growth by 50% and synergised with a MEK inhibitor to dramatically reduce growth. This study suggests inactivation of RNF43 and ZNRF3 is important in serrated tumorigenesis and has identified a potential therapeutic strategy for this cancer subtype. PMID- 27661108 TI - Acquired resistance to venetoclax (ABT-199) in t(14;18) positive lymphoma cells. AB - The chromosomal translocation t(14;18) in follicular lymphoma (FL) is a primary oncogenic event resulting in BCL-2 over-expression. This study investigates activity of the BH3 mimetic venetoclax (ABT-199), which targets BCL-2, and mechanisms of acquired resistance in FL.The sensitivity of FL cells to venetoclax treatment correlated with BCL-2/BIM ratio. Cells with similar expression of anti apoptotic proteins, but with higher levels of BIM were more sensitive to the treatment. Venetoclax induced dissociation of BCL-2/ BIM complex and a decrease in mitochondrial potential. Interestingly the population of cells that survived venetoclax treatment showed increased p-ERK1/2 and p-BIM (S69), as well as a decrease in total BIM levels. Venetoclax resistant cells initially showed elevated levels of p-AKT and p-Foxo1/3a, a dissociation of BIM/BCL-2/BECLIN1 complex, and a decrease in SQSTM1/p62 level (indicating increased autophagy) together with a slight decline in BIM expression. After stable resistant cell lines were established, a significant reduction of BCL-2 levels and almost total absence of BIM was observed.The acquisition of these resistance phenotypes could be prevented via selective ERK/AKT inhibition or anti-CD20 antibody treatment, thus highlighting possible combination therapies for FL patients. PMID- 27661109 TI - IMPA2 polymorphisms and risk of ischemic stroke in a northwest Han Chinese population. AB - Genetic association analysis has suggested that IMPA2 is a susceptibility gene for ischemic stroke (IS). To explore the association between IMPA2 polymorphisms and the risk of IS in a Han Chinese population, candidate gene association was performed using data from a case-control study of 488 IS patients and 503 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association, and associations were evaluated under dominant, recessive, and additive genetic models using PLINK software. There was a statistically significant difference in the "TC" genotype frequency of the IMPA2 polymorphism rs589247, between cases and controls (50.0% vs. 45.3%). Under the dominant model, rs589247 was associated with an increased risk of IS (OR=1.32, 95%CI: 1.01-1.73; P=0.040). There were no other associations between any of the seven additional IMPA2 polymorphisms and IS risk. This study is the first to find a correlation between an IMPA2 polymorphism and IS risk in a northwest Han Chinese population. These results may help to elucidate the molecular pathogenesis of this disease, and could potentially be used to predict IS risk. However, further studies are still needed to validate this association in other populations and with larger sample sizes. PMID- 27661110 TI - Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer. AB - In patients with colorectal cancer (CRC), local and systemic inflammatory responses have been extensively reported to associate with cancer survival. However, the specific signalling pathways responsible for inflammatory responses are not clear. The PTEN/Akt pathway is a plausible candidate as it may play a role in mediating inflammation via COX-2, and has been associated with cancer progression. This study therefore examined the relationship between tumour PTEN/Akt/COX-2 expression, inflammatory responses and survival in CRC patients using a tissue microarray.In 201 CRC patients, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (12.0yrs v 7.3yrs, P=0.032), poorer differentiation (P=0.032), venous invasion (P=0.008) and peritoneal involvement (P=0.004). Patients were stratified for peri-nuclear expression of COX-2 to examine associations with inflammatory responses. In patients with absent peri-nuclear COX-2 expression, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (11.9yrs v 5.4yrs, P=0.001), poorer differentiation (P=0.018), venous invasion (P=0.003) and peritoneal involvement (P=0.001). However, no associations were seen with either the local or systemic inflammatory responses.In CRC patients, tumour-specific PTEN/Akt pathway activation was significantly associated with poorer CSS, particularly when peri nuclear COX-2 expression was absent. However, activation of the PTEN/Akt pathway appears not to be responsible for the regulation of inflammatory responses. PMID- 27661111 TI - Association between tumor-stroma ratio and prognosis in solid tumor patients: a systematic review and meta-analysis. AB - Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor-stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle-Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors. PMID- 27661112 TI - Transfer of functional microRNAs between glioblastoma and microvascular endothelial cells through gap junctions. AB - Extensive invasion and angiogenesis are hallmark features of malignant glioblastomas. Here, we co-cultured U87 human glioblastoma cells and human microvascular endothelial cells (HMEC) to demonstrate the exchange of microRNAs that initially involve the formation of gap junction communications between the two cell types. The functional inhibition of gap junctions by carbenoxolone blocks the transfer of the anti-tumor miR-145-5p from HMEC to U87, and the transfer of the pro-invasive miR-5096 from U87 to HMEC. These two microRNAs exert opposite effects on angiogenesis in vitro. MiR-5096 was observed to promote HMEC tubulogenesis, initially by increasing Cx43 expression and the formation of heterocellular gap junctions, and secondarily through a gap-junction independent pathway. Our results highlight the importance of microRNA exchanges between tumor and endothelial cells that in part involves the formation of functional gap junctions between the two cell types. PMID- 27661113 TI - Sitagliptin may reduce prostate cancer risk in male patients with type 2 diabetes. AB - This retrospective cohort study evaluated the risk of prostate cancer associated with sitagliptin use in Taiwanese male patients with type 2 diabetes mellitus by using the reimbursement databases of the National Health Insurance. Male patients with newly diagnosed type 2 diabetes mellitus at an age >=25 years between 1999 and 2010 were recruited. A total of 37,924 ever users of sitagliptin and 426,276 never users were followed until December 31, 2011. The treatment effect of sitagliptin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Analyses were also conducted in a 1:1 matched pair cohort based on 8 digits of propensity score. Results showed that during follow-up, 84 ever users and 2,549 never users were diagnosed of prostate cancer, representing an incidence of 140.74 and 240.17 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) for ever users versus never users was 0.613 (0.493-0.763). The respective hazard ratio for the first, second, and third tertile of cumulative duration of sitagliptin use <5.9, 5.9-12.7 and >12.7 months was 0.853 (0.601-1.210), 0.840 (0.598-1.179) and 0.304 (0.191-0.483), respectively; and was 0.856 (0.603-1.214), 0.695 (0.475-1.016) and 0.410 (0.277-0.608) for cumulative dose <15,000, 15,000 33,600 and >33,600 mg, respectively. Findings were supported by analyses in the matched cohort. In conclusion, sitagliptin significantly reduces the risk of prostate cancer, especially when the cumulative duration is >12.7 months or the cumulative dose >33,600 mg. PMID- 27661114 TI - miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone. AB - Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA ("miRNA") downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b ("miR-135b") targets the 3' untranslated regions (UTRs) of Ppm1e. In human osteoblasticOB-6 cells and hFOB1.19 cells, forced expression of miR-135b downregulated Ppm1e and activated AMPK signaling. miR-135b also protected osteoblastic cells from Dex. shRNA-induced knockdown of Ppm1e similarly activated AMPK and inhibited Dex-induced damages. Intriguingly, in the Ppm1e-silenced osteoblastic cells, miR-135b expression failed to offer further cytoprotection against Dex. Notably, AMPK knockdown (via shRNA) or dominant negative mutation abolished miR-135b-induced AMPK activation and cytoprotection against Dex. Molecularly, miR-135b, via activating AMPK, increased nicotinamide adenine dinucleotide phosphate (NADPH) activity and inhibited Dex-induced oxidative stress. At last, we found that miR-135b level was increased in human necrotic femoral head tissues, which was correlated with Ppm1e downregulation and AMPK activation. There results suggest that miR-135b expression downregulates Ppm1e to activate AMPK signaling, which protects osteoblastic cells from Dex. PMID- 27661117 TI - High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers. AB - Proteins, as executives of genes' instructions, are responsible for cellular phenotypes. Integratingproteomics with gene microarray, we conducted this study to identify potential protein biomarkers of colorectal cancer (CRC). Isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between paired CRC and adjacent normal mucosa. Meanwhile, Affymetrix U133plus2.0 microarrays were used to perform gene microarray analysis. Verification experiments included immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay (ELISA) of selected proteins. Overall, 5469 differentially expressed proteins were detected with iTRAQ-MS from 24 matched CRC and adjacent normal tissues. And gene microarray identified 39859 differential genes from 52 patients. Of these, 3083 differential proteins had corresponding differentially expressed genes, with 245 proteins and their genes showed >1.5-fold change in expression level. Gene ontology enrichment analysis revealed that up-regulated proteins were more involved in cell adhesion and motion than down-regulated proteins. In addition, up-regulated proteins were more likely to be located in nucleus and vesicles. Further verification experiments with IHC confirmed differential expression levels of 5 proteins (S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1) between CRC and normal tissues. Besides, western blot showed a stepwise increase of annexin A3 abundance in normal colorectal mucosa, adenoma and CRC tissues. ELISAresults revealed significantly higher serum levels of S100 calcium-binding protein A9 and annexin A3 in CRC patients than healthy controls, validating diagnostic value of these proteins. Cell experiments showed that inhibition of annexin A3 could suppress CRC cell proliferation and aggressiveness. S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1 were probably potential biomarkers of colorectal cancer. Annexin A3 was a potentially valuable therapeutic target of CRC. PMID- 27661116 TI - Targeting Notch signaling as a novel therapy for retinoblastoma. AB - Retinoblastoma is the most common intraocular malignancy of childhood. Notch plays a key role in retinal cells from which retinoblastomas arise, and we therefore studied the role of Notch signaling in promoting retinoblastoma proliferation. Moderate or strong nuclear expression of Hes1 was found in 10 of 11 human retinoblastoma samples analyzed immunohistochemically, supporting a role for Notch in retinoblastoma growth. Notch pathway components were present in WERI Rb1 and Y79 retinoblastoma lines, with Jag2 and DLL4 more highly expressed than other ligands, and Notch1 and Notch2 more abundant than Notch3. The cleaved/active form of Notch1 was detectable in both lines. Inhibition of the pathway, achieved using a gamma-secretase inhibitor (GSI) or by downregulating Jag2, DLL4 or CBF1 using short hairpin RNA, potently reduced growth, proliferation and clonogenicity in both lines. Upregulation of CXCR4 and CXCR7 and downregulation of PI3KC2beta were identified by microarray upon Jag2 suppression. The functional importance of PI3KC2beta was confirmed using shRNA. Synergy was found by combining GSI with Melphalan at their IC50. These findings indicate that Notch pathway is active in WERI Rb1 and Y79, and in most human retinoblastoma samples, and suggest that Notch antagonists may represent a new approach to more effectively treat retinoblastoma. PMID- 27661115 TI - Ibrutinib synergizes with MDM-2 inhibitors in promoting cytotoxicity in B chronic lymphocytic leukemia. AB - OBJECTIVE: The aim of this study was to investigate the anti-leukemic activity of the Bruton tyrosine kinase inhibitor Ibrutinib in combination with the small molecule MDM-2 inhibitor Nutlin-3 in preclinical models. METHODS: The potential efficacy of the Ibrutinib/Nutlin-3 combination was evaluated in vitro in a panel of B leukemic cell lines (EHEB, JVM-2, JVM-3, MEC-1, MEC-2) and in primary B chronic lymphocytic leukemia (B-CLL) patient samples, by assessing cell viability, cell cycle profile, apoptosis and intracellular pathway modulations. Validation of the combination therapy was assessed in a B leukemic xenograft mouse model. RESULTS: Ibrutinib exhibited variable anti-leukemic activity in vitro and the combination with Nutlin-3 synergistically enhanced the induction of apoptosis independently from the p53 status. Indeed, the Ibrutinib/Nutlin-3 combination was effective in promoting cytotoxicity also in primary B-CLL samples carrying 17p13 deletion and/or TP53 mutations, already in therapy with Ibrutinib. Molecular analyses performed on both B-leukemic cell lines as well as on primary B-CLL samples, while confirming the switch-off of the MAPK and PI3K pro-survival pathways by Ibrutinib, indicated that the synergism of action with Nutlin-3 was independent by p53 pathway and was accompanied by the activation of the DNA damage cascade signaling through the phosphorylation of the histone protein H2A.X. This observation was confirmed also in the JVM-2 B leukemic xenograft mouse model. CONCLUSIONS: Taken together, our data emphasize that the Ibrutinib/Nutlin-3 combination merits to be further evaluated as a therapeutic option for B-CLL. PMID- 27661118 TI - Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation. AB - HCV life cycle is strictly correlated with the hepatocyte lipid metabolism; moreover, the progression of HCV chronic hepatitis is accelerated by the presence of liver steatosis. Among the steatogenic genes deregulated during the HCV infection one of the most attractive is the Small Heterodimer Protein 1 (SHP1; NR0B2), that is involved in a remarkable number of metabolic functions. HCV NS5A is an essential and integral component of the HCV membranous-web replicon complex (RC) and plays an essential role to transfer the viral genome from the RCs to the surface of the lipid droplets (LDs) that, in turn, play a key function during HCV life cycle.With the help of a HCV infection model, we demonstrate a functional interaction between SHP1 and HCV NS5A protein. SHP1 silencing (siSHP1) reversed the pro-oncogenic effects of HCV infection, inducing a significant decrease in liver lipid accumulation and in NS5A protein expression. Moreover, siSHP1 causes a strong modulation of some genes involved in HCV-related EMT, such as: HNF4, a central regulators of hepatocyte differentiation, E-Cadherin, SNAILs.Our data suggest that SHP1 results not only to be strictly connected to the pathogenesis of HCV-related liver steatosis, but also to its progression towards the liver transformation. PMID- 27661120 TI - FRMD6 inhibits human glioblastoma growth and progression by negatively regulating activity of receptor tyrosine kinases. AB - FRMD6 is an Ezrin/Radixin/Moesin (ERM) family protein and a human homologue of Drosophila expanded (ex). Ex functions in parallel of Drosophila merlin at upstream of the Hippo signaling pathway that controls proliferation, apoptosis, tissue regeneration, and tumorigenesis. Even though the core kinase cascade (MST1/2-Lats1/2-YAP/TAZ) of the Hippo pathway has been well established, its upstream regulators are not well understood. Merlin promotes activation of the Hippo pathway. However, the effect of FRMD6 on the Hippo pathway is controversial. Little is known about how FRMD6 functions and the potential role of FRMD in gliomagenesis and glioblastoma (GBM) progression. We demonstrate for the first time that FRMD6 is down-regulated in human GBM cells and tissues and that increased FRMD6 expression inhibits whereas FRMD6 knockdown promotes GBM cell proliferation/invasion in vitro and GBM growth/progression in vivo. Furthermore, we demonstrate that unlike increased expression of merlin, which enhances the stress induced activation of the Hippo pathway, increased FRMD6 expression displays little effect on the pathway. In contrast, we show that FRMD6 inhibits activation of a couple of receptor tyrosine kinases (RTKs) including c Met and PDGFR and their downstream Erk and AKT kinases. Moreover, we show that expression of constitutively active c-Met, the TPR-Met fusion protein, largely reverses the anti-GBM effect of FRMD6 in vivo, suggesting that FRMD6 functions at least partially through inhibiting activity of RTKs especially c-Met. These results establish a novel function of FRMD6 in inhibiting human GBM growth and progression and uncover a novel mechanism by which FRMD6 exerts its anti-GBM activity. PMID- 27661119 TI - Paraoxonase 3 inhibits cell proliferation and serves as a prognostic predictor in hepatocellular carcinoma. AB - Paraoxonase 3 (PON3) exerts prominent anti-inflammation and anti-oxidation properties mainly at the cellular level, and is primarily expressed in the liver. However, its role in HCC remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of PON3 in HCC. PON3 mRNA and protein levels were respectively determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) of tissue microarray. We found that PON3 was downregulated in most HCCs. Kaplan-Meier and log-rank test showed that PON3 downregulation predicted shorter recurrence-free survival (RFS) and overall survival (OS) time in all HCC patients, especially early-stage HCC patients. Cox regression analysis revealed that the PON3 downregulation was an independent risk factor for RFS and OS. Gain- and loss-of-function experiments revealed that PON3 suppressed cell proliferation in vivo and in vitro, which was attributed to its cell-cycle arrest effect. In addition, microarray analysis showed that some pro proliferative genes were elevated when PON3 was knockdown, and these genes possibly involved in the underlying mechanisms. In conclusion, our studies reveal the cell proliferation inhibitory function of PON3 and offer a potential prognostic predictor and therapeutic target for HCC. PMID- 27661122 TI - A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk. AB - Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC.We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs4939827/18q21.1, rs10795668/10p14, rs4444235/14q22.2 and rs4779584/ 15q13.3, were selected for the current study from the qualified studies. Then meta-analyses based on larger sample sizes with average of 33,000 CRC cases and 34,000 controls were performed to assess the association between SNPs and CRC risk. Heterogeneity among studies and publication bias were assessed by the chi2-based Q statistic test Begg's funnel plot or Egger's test, respectively.Our meta-analysis confirmed significant associations of the five SNPs with CRC risk under different genetic models. Two risk variants at rs6983267 {Odds Ratio (OR) 1.388, 95% Confidence Interval (CI) 1.180-1.8633} and rs10795668 (OR 1.323, 95% CI 1.062-1.648) had the highest ORs in homogeneous model. While ORs of the other three variants at rs4939827 {OR 1.298, 95% CI 1.135-1.483}, rs4779584 (OR 1.261, 95% CI 1.146-1.386) and rs4444235 (OR 1.160, 95% CI 1.106 1.216) were also statistically significant. Sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results. PMID- 27661121 TI - Secondary nuclear targeting of mesoporous silica nano-particles for cancer specific drug delivery based on charge inversion. AB - A novel multifunctional nano-drug delivery system based on reversal of peptide charge was successfully developed for anticancer drug delivery and imaging. Mesoporous silica nano-particles (MSN) ~50 nm in diameter were chosen as the drug reservoirs, and their surfaces were modified with HIV-1 transactivator peptide fluorescein isothiocyanate (TAT-FITC) and YSA-BHQ1. The short TAT peptide labeled with FITC was used to facilitate intranuclear delivery, while the YSA peptide tagged with the BHQ1 quencher group was used to specifically bind to the tumor EphA2 membrane receptor. Citraconic anhydride (Cit) was used to invert the charge of the TAT peptide in neutral or weak alkaline conditions so that the positively charged YSA peptide could combine with the TAT peptide through electrostatic attraction. The FITC fluorescence was quenched by the spatial approach of BHQ1 after the two peptides bound to each other. However, the Cit-amino bond was unstable in the acidic atmosphere, so the positive charge of the TAT peptide was restored and the positively charged YSA moiety was repelled. The FITC fluorescence was recovered after the YSA-BHQ1 moiety was removed, and the TAT peptide led the nano-particles into the nucleolus. This nano-drug delivery system was stable at physiological pH, rapidly released the drug in acidic buffer, and was easily taken up by MCF-7 cells. Compared with free doxorubicin hydrochloride at an equal concentration, this modified MSN loaded with doxorubicin molecules had an equivalent inhibitory effect on MCF-7 cells. This nano-drug delivery system is thus a promising method for simultaneous cancer diagnosis and therapy. PMID- 27661123 TI - WW45, a Gli1 binding protein, negatively regulated Hedgehog signaling in lung cancer. AB - Over-expression of Gli1 is very common in lung cancer. However, the underlying molecular mechanism remains largely unknown. Here, using mass spectrum, we have identified WW45 as a binding partner of Gli1. WW45 interacted with Gli1, promoted its ubiquitination and inhibited the expression of its target genes. In the functional studies, WW45 inhibited the growth and migration of lung cancer cells. Knocking down the expression of WW45 promoted the growth and migration of lung cancer cells, which was rescued by down-regulation of Gli1. Moreover, over expression of WW45 inhibited the tumorigenesis in a de novo lung cancer tumorigenesis mouse model (LKB-Ras) as well as the expression of Gli1. Also over expression of WW45 improved the survival of these mice. In addition, the expression of WW45 was down-regulated in the clinical lung cancer samples, which was inversely correlated with the expression of Gli1. Taken together, this study demonstrated the suppressive roles of WW45 in lung cancer by inhibiting the Hedgehog/Gli1 signaling. PMID- 27661125 TI - Outcomes in adult critically ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hematologie (GRRR-OH). AB - PURPOSE: Whether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and prognostic factor. METHODS: Systematic review and meta-analysis. Studies on adult cancer patients and intensive care units were searched on PubMed and Cochrane databases (2005-2015). Summary estimates of mortality risk differences were calculated using the random-effects model. RESULTS: Among the 1,528 citations identified, 38 studies reporting on 6,054 patients (2,097 neutropenic patients) were included. Median mortality across the studies was 54% [45-64], with unadjusted mortality in neutropenic and non-neutropenic critically ill patients of 60% [53-74] and 47% [41-68], respectively. Overall, neutropenia was associated with a 10% increased mortality risk (6%-14%; I2 = 50%). The admission period was not associated with how neutropenia affected mortality. Mortality significantly dropped throughout the study decade [-11% (-13.5 to 8.4)]. This mortality drop was observed in non-neutropenic patients [-12.1% ( 15.2 to -9.0)] but not in neutropenic patients [-3.8% (-8.1 to +5.6)].Sensitivity analyses disclosed no differences in underlying malignancy, mechanical ventilation use, or Granulocyte-colony stimulating factor use. Seven studies allowed the adjustment of severity results (1,350 patients). Although pooled risk difference estimates were similar to non-adjusted results, there was no significant impact of neutropenia on mortality (risk difference of mortality, 9%; 95% CI, -15 to +33). CONCLUSION: Although the unadjusted mortality of neutropenic patients was 11% higher, this effect disappeared when adjusted for severity. Therefore, when cancer patients become critically ill, neutropenia cannot be considered as a decision-making criterion. PMID- 27661126 TI - MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28. AB - Colorectal cancer (CRC) is one of the most common prevalent cancer types worldwide. MicroRNAs (miRNAs or miRs) have been demonstrated to play crucial roles in the development, metastasis and drug resistance of CRC. In the present study, a strikingly elevated expression of miR-552 was determined in CRC tumor tissues and cells by a miRNA profiling analysis. Importantly, the gene of A Disintegrin And Metalloprotease (ADAM) family member 28 (ADAM28) was identified as a target of miR-552, which was further validated in terms of genetic dual luciferase report assay. Furthermore, an inhibition of miR-552 in LOVE and LS174T CRC cells by transducing miR-552 inhibitor (antagomiR-552) with a lentiviral vector exhibited an ability to reduce cell proliferation, migration and clonogenicity. Moreover, both LOVO and LS174T cells stably expressing miR-552 inhibitor displayed a decreased ability to develop tumors in a murine xenograft model in vivo. In contrast, a knockdown of ADAM28 by short hairpin RNA could reverse the antagomiR-552-induced inhibition of metastatic features of CRC cells in vitro. These results suggested that miR-552 is an oncomir able to promote CRC metastasis in part through a mechanism of targeting ADAM28, which may be a novel target for CRC treatment and warrants for further investigation. PMID- 27661127 TI - Long-term monitoring of Ca2+ dynamics in C. elegans pharynx: an in vivo energy balance sensor. AB - Ca2+ is a key signal transducer for muscle contraction. Continuous in vivo monitoring of intracellular Ca2+-dynamics in C. elegans pharynx muscle revealed surprisingly complex Ca2+ patterns. Despite the age-dependent decline of pharynx pumping, we observed unaltered fast Ca2+ oscillations both in young and old worms. In addition, sporadic prolonged Ca2+ increases lasting many seconds or minutes were often observed in between periods of fast Ca2+ oscillations. We attribute them to the inhibition of ATP-dependent Ca2+-pumps upon energy depletion. Accordingly, food deprivation largely augmented the frequency of prolonged [Ca2+] increases. However, paradoxically, prolonged [Ca2+] increases were more frequently observed in young worms than in older ones, and less frequently observed in energy-deficient mitochondrial respiratory chain nuo-6 mutants than in wild-type controls. We hypothesize that young animals are more susceptible to energy depletion due to their faster energy consumption rate, while nuo-6 mutants may keep better the energy balance by slowing energy consumption. Our data therefore suggest that the metabolic state of the pharynx during feeding stimulation depends mainly on the delicate balance between the instant rates of energy production and consumption. Thus, in vivo monitoring of muscle Ca2+ dynamics can be used as a novel tool to study cellular energy availability. PMID- 27661130 TI - Drugging the "undruggable" DNA-binding domain of STAT3. PMID- 27661128 TI - B lymphocytes as direct antigen-presenting cells for anti-tumor DNA vaccines. AB - In spite of remarkable preclinical efficacy, DNA vaccination has demonstrated low immunogenicity in humans. While efforts have focused on increasing cross presentation of DNA-encoded antigens, efforts to increase DNA vaccine immunogenicity by targeting direct presentation have remained mostly unexplored. In these studies, we compared the ability of different APCs to present antigen to T cells after simple co-culture with plasmid DNA. We found that human primary peripheral B lymphocytes, and not monocytes or in vitro derived dendritic cells (DCs), were able to efficiently encode antigen mRNA and expand cognate tumor antigen-specific CD8 T cells ex vivo. Similarly, murine B lymphocytes co-cultured with plasmid DNA, and not DCs, were able to prime antigen-specific T cells in vivo. Moreover, B lymphocyte-mediated presentation of plasmid antigen led to greater Th1-biased immunity and was sufficient to elicit an anti-tumor effect in vivo. Surprisingly, increasing plasmid presentation by B cells, and not cross presentation of peptides by DCs, further augmented traditional plasmid vaccination. Together, these data suggest that targeting plasmid DNA to B lymphocytes, for example through transfer of ex vivo plasmidloaded B cells, may be novel means to achieve greater T cell immunity from DNA vaccines. PMID- 27661129 TI - High fat diet exacerbates Alzheimer's disease-related pathology in APPswe/PS1 mice. AB - Alzheimer's disease (AD) is mainly characterized by the accumulation and aggregation of amyloid-beta (Abeta) peptides in brain parenchyma and cerebral microvasculature. Unfortunately, the exact causes of the disease are still unclear. However, blood-brain barrier (BBB) dysfunction and activation of inflammatory pathways are implicated in AD pathogenesis. Importantly, advanced age and high fat diet, two major risk factors associated with AD, were shown to deeply affect BBB function and modulate the immune response. As such, this study evaluated the impact of age and high fat diet on AD progression. For this purpose, 3 (i.e. young) and 12 (i.e. aged) months old APPswe/PS1 mice were fed for 4 months with a high fat diet (i.e. Western diet (WD)) or normal diet. Interestingly, neurobehavioral tests revealed that WD accelerates age-associated cognitive decline without affecting parenchymal Abeta. Nonetheless, WD decreases matrix metalloproteinase-9 enzymatic activity and brain-derived neurotrophic factor mRNA and protein levels in brain, suggesting loss of synaptic plasticity. In the periphery, WD promotes systemic inflammation by increasing the levels of blood-circulating monocytes and monocyte chemotactic protein-1 production, which is accompanied by an augmentation of oxidized-low density lipoprotein levels in blood circulation. At the BBB, WD potentiates the age-induced increase of Abeta 1 40 accumulation and exacerbates the oxidative stress, specifically in cerebral microvasculature. These effects were accompanied by the dysfunction of pericytes, thus altering BBB functionality without compromising its integrity. Our study provides new insights into the implication of high fat diet in accelerating the cognitive decline in AD. PMID- 27661131 TI - Renal denervation attenuates aldosterone expression and associated cardiovascular pathophysiology in angiotensin II-induced hypertension. AB - The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II) induced hypertension. Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II subcutaneous infusion (200ng/kg/min) in male Sprague-Dawley rats. Bilateral RDN blunted Ang II-induced hypertension and ameliorated the mesenteric vascular dysfunction. Cardiovascular hypertrophy in response to Ang II was significantly attenuated by RDN as shown by histopathology and transthoracic echocardiography. Moreover, Ang II-induced vascular and myocardial inflammation and fibrosis were suppressed by RDN with concurrent decrease in fibronectin and collagen deposition, macrophage infiltration, and MCP-1 expression. Interestingly, RDN also inhibited Ang II-induced aldosterone expression in the plasma, kidney and heart. This was associated with the reduction of calcitonin gene-related peptide (CGRP) in the adrenal gland. Ang II promoted aldosterone secretion which was partly attenuated by CGRP in the adrenocortical cell line, suggesting a protective role of CGRP in this model. Activation of transforming growth factor-beta (TGF-beta)/Smad and mitogen-activated protein kinases (MAPKs) signaling pathway was both inhibited by RDN especially in the heart. These results suggest that the regulation of the renal sympathetic nerve in Ang II induced hypertension and associated cardiovascular pathophysiological changes is likely mediated by aldosterone, with CGRP involvement. PMID- 27661133 TI - Presence of Toxoplasma gondii in Pork Intended for Human Consumption in Tropical Southern Mexico. AB - BACKGROUND: Toxoplasmosis is caused by the protozoon Toxoplasma gondii, which is one of the most widespread parasites that infect animals and humans worldwide. One of the main routes of infection for humans is through the consumption of infected meat containing bradyzoites in tissue cysts. Pork is one of the foremost meat types associated with outbreaks of acute toxoplasmosis in humans. MATERIALS AND METHODS: Sixty blood samples were collected from finished pigs at slaughter and their sera was evaluated by an indirect-IgG ELISA. Matched muscle samples were obtained from the tongue and loin. Whole blood and tissue samples were evaluated to search for T. gondii DNA using a nested-polymerase chain reaction. RESULTS: Seroprevalence of T. gondii was 96.6% (58/60) of sampled pigs. Meanwhile, T. gondii DNA was present in 23.21% of tongue tissue samples (13/56), 7% of loin tissues (4/57), and 0% in blood samples (0/44), respectively. Two pigs were serologically indeterminate. CONCLUSION: This is the first report of the presence of T. gondii DNA in tissue samples obtained from finalized pigs. Results from the present study suggest a high exposure to T. gondii in pigs intended for human consumption from the tropical region of Mexico. Thus, the consumption of some undercooked pork meat meals typical from the southern region of Mexico could represent a significant risk for acquiring infection for the human population. PMID- 27661132 TI - Systems pharmacology and enhanced pharmacodynamic models for understanding antibody-based drug action and toxicity. AB - Pharmacokinetic (PK) and pharmacodynamic (PD) models seek to describe the temporal pattern of drug exposures and their associated pharmacological effects produced at micro- and macro-scales of organization. Antibody-based drugs have been developed for a large variety of diseases, with effects exhibited through a comprehensive range of mechanisms of action. Mechanism-based PK/PD and systems pharmacology models can play a major role in elucidating and integrating complex antibody pharmacological properties, such as nonlinear disposition and dynamical intracellular signaling pathways triggered by ligation to their cognate targets. Such complexities can be addressed through the use of robust computational modeling techniques that have proven powerful tools for pragmatic characterization of experimental data and for theoretical exploration of antibody efficacy and adverse effects. The primary objectives of such multi-scale mathematical models are to generate and test competing hypotheses and to predict clinical outcomes. In this review, relevant systems pharmacology and enhanced PD (ePD) models that are used as predictive tools for antibody-based drug action are reported. Their common conceptual features are highlighted, along with approaches used for modeling preclinical and clinically available data. Key examples illustrate how systems pharmacology and ePD models codify the interplay among complex biology, drug concentrations, and pharmacological effects. New hybrid modeling concepts that bridge cutting-edge systems pharmacology models with established PK/ePD models will be needed to anticipate antibody effects on disease in subpopulations and individual patients. PMID- 27661136 TI - Society of Biomolecular Imaging and Informatics Special Issue, October 2016. PMID- 27661135 TI - miR-378a-3p promotes differentiation and inhibits proliferation of myoblasts by targeting HDAC4 in skeletal muscle development. AB - Muscle development, or myogenesis, is a highly regulated, complex process. A subset of microRNAs (miRNAs) have been identified as critical regulators of myogenesis. Recently, miR-378a was found to be involved in myogenesis, but the mechanism of how miR-378a regulates the proliferation and differentiation of myoblasts has not been determined. We found that miR-378a-3p expression in muscle was significantly higher than in other tissues, suggesting an important effect on muscle development. Overexpression of miR-378a-3p increased the expression of MyoD and MHC in C2C12 myoblasts both at the level of mRNA and protein, confirming that miR-378a-3p promoted muscle cell differentiation. The forced expression of miR-378a-3p promoted apoptosis of C2C12 cells as evidenced by CCK-8 assay and Annexin V-FITC/PI staining results. Through TargetScan, histone acetylation enzyme 4 (HDAC4) was identified as a potential target of miR-378a-3p. We confirmed targeting of HDAC4 by miR-378a-3p using a dual luciferase assay and western blotting. Our RNAi analysis results also showed that HDAC4 significantly promoted differentiation of C2C12 cells and inhibited cell survival through Bcl 2. Therefore, we conclude that miR-378a-3p regulates skeletal muscle growth and promotes the differentiation of myoblasts through the post-transcriptional down regulation of HDAC4. PMID- 27661140 TI - Unions cite report and call for delay. AB - Health care unions have cited a report from the Government's watchdog on public spending as further evidence of the urgent need to slow down NHS reforms. PMID- 27661138 TI - Mechanisms of hormonal regulation of the peripheral circadian clock in the colon. AB - Colonic function is controlled by an endogenous clock that allows the colon to optimize its function on the daytime basis. For the first time, this study provided evidence that the clock is synchronized by rhythmic hormonal signals. In rat colon, adrenalectomy decreased and repeated applications of dexamethasone selectively rescued circadian rhythm in the expression of the clock gene Per1. Dexamethasone entrained the colonic clock in explants from mPer2Luc mice in vitro. In contrast, pinealectomy had no effect on the rat colonic clock, and repeated melatonin injections were not able to rescue the clock in animals maintained in constant light. Additionally, melatonin did not entrain the clock in colonic explants from mPer2Luc mice in vitro. However, melatonin affected rhythmic regulation of Nr1d1 gene expression in vivo. The findings provide novel insight into possible beneficial effects of glucocorticoids in the treatment of digestive tract-related diseases, greatly exceeding their anti-inflammatory action. PMID- 27661137 TI - The Impact of Health Literacy on Surgical Outcomes Following Radical Cystectomy. AB - Health literacy is the ability to obtain, comprehend, and act on medical information and is an independent predictor of health outcomes in patients with chronic health conditions. However, little has been reported regarding the potential association of health literacy and surgical outcomes. We hypothesized that patient complications after radical cystectomy would be associated with health literacy. In a sample of 368 patients, we found that higher health literacy scores (as determined by the Brief Health Literacy Screen) were associated with decreased odds of developing minor complications (odds ratio = 0.90, 95% confidence interval [0.83, 0.97]). Health literacy should be considered when caring for patients undergoing radical cystectomy and should serve as a potential indicator of the need for additional resources to improve postoperative outcomes. PMID- 27661139 TI - Mapping the MMPI-2-RF Substantive Scales Onto Internalizing, Externalizing, and Thought Dysfunction Dimensions in a Forensic Inpatient Setting. AB - Contemporary models of psychopathology-encompassing internalizing, externalizing, and thought dysfunction factors-have gained significant support. Although research indicates the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008 /2011) measures these domains of psychopathology, this study addresses extant limitations in MMPI-2-RF diagnostic validity research by examining associations between all MMPI-2-RF substantive scales and broad dichotomous indicators of internalizing, externalizing, and thought dysfunction diagnoses in a sample of 1,110 forensic inpatients. Comparing those with and without internalizing diagnoses, notable effects were observed for Negative Emotionality/Neuroticism-Revised (NEGE-r), Emotional/Internalizing Dysfunction (EID), Dysfunctional Negative Emotions (RC7), Demoralization (RCd), and several other internalizing and somatic/cognitive scales. Comparing those with and without thought dysfunction diagnoses, the largest hypothesized differences occurred for Thought Dysfunction (THD), Aberrant Experiences (RC8), and Psychoticism-Revised (PSYC-r), although unanticipated differences were observed on internalizing and interpersonal scales, likely reflecting the high prevalence of internalizing dysfunction in forensic inpatients not experiencing thought dysfunction. Comparing those with and without externalizing diagnoses, the largest effects were for Substance Abuse (SUB), Antisocial Behavior (RC4), Behavioral/Externalizing Dysfunction (BXD), Juvenile Conduct Problems (JCP), and Disconstraint-Revised (DISC-r). Multivariate models evidenced similar results. Findings support the construct validity of MMPI-2-RF scales as measures of internalizing, thought, and externalizing dysfunction. PMID- 27661142 TI - Applications rise for degree courses. AB - Applications for nursing degree courses at polytechnics have risen by over 20 per cent since last year, with applications for courses at universities up by 7.3 per cent. PMID- 27661143 TI - ? AB - Charitable heights: Lindsay Fraser, Night Sister at St Thomas' Hospital, looks anxious before abseiling from the hospital's roof to raise cash for Operation Raleigh. She will travel on a research and conservation project to Guyana. PMID- 27661144 TI - Overtime scrapped for bank contracts. AB - Management at Liverpool's Alder Hey Hospital Trust have angered nurses by scrapping overtime and asking them instead to fill service gaps as bank staff. PMID- 27661145 TI - ? AB - Blood donor: Health Minister Virginia Bottomley gives blood at the West End Donor Centre in London. Her visit was part of a summer campaign to encourage blood donors to keep their appointments over the holiday period. PMID- 27661147 TI - Tragic death of dedicated nurse. AB - The death of a dedicated Inverness charge nurse who took an overdose of paracetamol during a moment of stress has highlighted the need for better staff support systems in the health service, it was claimed last week. PMID- 27661149 TI - Totally inadequate' transitional funding. AB - Nurses have described as 'totally inadequate' the Government's announcement of L28 million loans to selected health authorities, intended to speed the movement of patients from outdated mental health hospitals into the community. PMID- 27661148 TI - ? AB - Casualty shift: The cast of BBC l's Casualty will include some new faces when the service returns for a 15-week run on Friday, September 6. PMID- 27661150 TI - Residential care. AB - Nurses have warmly welcomed Labour's plan for national standards in residential and nursing care. PMID- 27661153 TI - Nurses may help people to enjoy their old age. AB - Attitudes to the care of elderly people must change if they are to enjoy the experiences of old age, a new report argues. PMID- 27661152 TI - Education. AB - Fourteen nurse teachers from Pakistan will be undertaking specialist training at the Sheffield and North Trent College of Nursing and Midwifery, which has won a five-year contract with Overseas Development Administration to develop post- basic nurse education in Pakistan. PMID- 27661155 TI - Non-union association initiated in Somerset. AB - Somerset nurses are forming their own non-union organisation as a forum to cross local Trust boundaries and to discuss national issues. PMID- 27661154 TI - Libraries. AB - The English National Board has received a L95,000 donation from the General Nursing Council Trust to develop libraries within the estimated 160 Colleges of Nursing and Midwifery in England. PMID- 27661156 TI - ? AB - Judges Tony Thompson, left, and Justus Akinsanya are pictured at the BUPA Nursing/Nursing Standard Nurse 91 Awards judging day. Prime Minister John Major will present the awards to the winning nurses on September 17. PMID- 27661158 TI - Oral rehydration may be be widely under used. AB - Oral rehydration of children suffering from the effects of diarrhoea is seen to be less preferable than the intravenous method, according to a paper published in the British Medical Journal, despite an apparent prejudice against it. PMID- 27661159 TI - Bowel cancer screening could reduce check-ups. AB - Screening might soon be available for people who are susceptible to inherited forms of bowel cancer, according to a report in New Scientist. PMID- 27661160 TI - Toxoplasmosis gondii risk to the fetus. AB - Claims that maternal immunity developing before conception protects the fetus from congenital toxoplasmosis have been questioned by doctors reporting a case in France. Toxoplasmosis gondii organisms shown in a section of liver tissue. Cats are the definitive host but infection can also occur through undercooked meat. PMID- 27661161 TI - Complications beset keratomy procedure. AB - Minor complications following surgery to correct short-sightedness affect up to one third of patients and in rare cases have caused blindness, says a report from the Consumers' Association. PMID- 27661162 TI - Tests for hepatitis C to improve blood safety. AB - The Department of Health has announced that from September 1 all blood donations will be tested for hepatitis C using recently developed tests. PMID- 27661163 TI - RCN Council. AB - Nominations for election to the Royal College of Nursing Council have closed with the following people being returned unopposed to represent their regions: Judith Cosker Hunter (Northern); Stuart Mahon (Trent); Sally Gooch (North East Thames); Peter Fox (Oxford); Lesley Anne Chivers (South Western). PMID- 27661164 TI - Committees 'should include nurses'. AB - New guidelines on the role and function of Local Research Ethics Committees were launched by the Department of Health last week. PMID- 27661165 TI - Hancock urges change in attitudes. AB - The Royal College of Nursing has launched a new guide to promote occupational health in the workplace. PMID- 27661167 TI - Obituary. AB - Professor Gerry Simon, the University of Birmingham's first Professor in Mental Handicap, died last month at the age of 70. He was instrumental in pioneering services for people with learning difficulties during the 1960s. Throughout his career, Professor Simon encouraged nursing staff to use their skills to bring about change and he supported nurses' efforts to move away from entrenched institutional practices. PMID- 27661168 TI - Levels of consistency in alcohol intake. AB - Patients and their spouses or relatives might under- or over-report alcohol consumption, and spouses may simply not know how much their partners drink. PMID- 27661169 TI - GPs elucidate chronic fatigue syndrome. AB - Patients suffering from chronic fatigue syndrome appear to be a distinct group for GPs and might represent a substantial part of their workload. PMID- 27661171 TI - Stopping treatment for hypertension sufferers. AB - The assumption that treatment for hypertension will be necessary for life has been questioned by researchers. PMID- 27661170 TI - Progestagen reduces cancer risk in HRT. AB - Progestagen use for ten or more days per cycle can reduce the excess risk of endometrial cancer associated with longterm postmenopausal oestrogen use. PMID- 27661172 TI - Aerodynamic riding - proceed with caution. AB - Handlebars added to bicycles so that a more aerodynamic riding position can be adopted may have serious health risks. PMID- 27661174 TI - 'What if a baby comes?' AB - The most welcome sound Mariam Al Raqem has ever heard was the sound of running feet. At 11.30 one night she was startled by a noise outside her flat. There was no electricity, so with the aid of a torch, Mariam's son went to the door to investigate. 'Mummy, they're running away.' She could not believe the Iraqi army was fleeing Kuwait. But an hour later her neighbour came round to say it was true. Kuwait was free. PMID- 27661175 TI - Ready to make the change. AB - The UKCC is pressing ahead with plans to radically alter post-basic education and practice after positive feedback during months of consultation. PMID- 27661173 TI - Between the lines. AB - If recent reports in the media are anything to go by, then there has been a huge increase in 'elder abuse' during the past few years. Common sense tells us this isn't the case; abuse of elderly people has been happening for years but awareness of the issue is now increasing. PMID- 27661176 TI - Misinterpreting client contracts. AB - I Barbara Eunson's letter questioning the credentials of private therapists (Nursing Standard Points of View I August 14) gave me cause I for concern. Counsellors do, of course, have a professional body, with its own ethics and practice codes. PMID- 27661178 TI - ? PMID- 27661177 TI - Stimulating nevertheless. AB - No doubt, returning from my holiday placed me in a particularly irritable and sensitive mood, no doubt and Barry Clifton's article 'Renaissance general nurse' (Nursing Standard Viewpoint August 7), was intended to provoke, if not irritate. PMID- 27661179 TI - Critical view of nursing care. AB - I feel I have to make three points in response to the anonymous article 'A caring profession?' (Nursing Standard August 7). PMID- 27661180 TI - Information exchange. AB - I am an RNMH and manager of a hospital facing closure, during which period, people with varying degrees of mental handicaps will be transferred to community housing accommodation geared to meet the needs of the individual. PMID- 27661181 TI - Memo to workers. AB - Dear Colleague We imagine that you must be becoming wary of letters addressed to you as ??dear colleague', that are from people who you do not see as sharing your caring profession or as having any connection with wards and patients at all and who, as far as you can see, have as their chief goal in life your disempowerment and devaluation. PMID- 27661182 TI - A new age Nightingale. AB - There are not that many non-conformists in the upper echelons of the nursing world today but Dr Helen Ference, the American Director of the Nightingale Society, is one of them. PMID- 27661183 TI - The TLA phenomenon. AB - I recently attended a Nursing Standard promotion evening in Leeds and as is often the case while socialising, the opportunity was used to put the NHS to rights. PMID- 27661184 TI - The Skills of Training, 2nd edition The Skills of Training, 2nd edition 2nd Edition L Rae Gower 300pp L28.50 0-566-02902-2 [Formula: see text]. AB - The Skills of Training: A Guide for Managers and Practitioners, Second Edition contains many useful hints for educationalists, trainers and students in that field, but the book is not written in a style that would be helpful to managers. PMID- 27661185 TI - Competitive health care in europe Competitive health care in europe Casparie A Hermans H Paelinck J editors Dartmouth Publishing Co 320pp L35 1-85521-186-6 [Formula: see text]. AB - The United Kingdom has been a member of the EEC since 1972. The first EEC Nursing Directives were published in 1977, and, yet, in the intervening years since those historic events, there has been relatively little in-depth analysis of the real issues affecting health care in the now EC outside the working documents of the European Commission or Parliament. PMID- 27661187 TI - Summer daze. PMID- 27661186 TI - The quality of dying The quality of dying Bender M Lloyd C Cooper A A Cooper Winslow Press 108pp L18.95 0-863-8807-7 [Formula: see text]. AB - In The Quality of Dying, the scene is set with the authors', that is, Mike Bender, Christa Lloyd and Alison Cooper, own research. PMID- 27661188 TI - Gossip. PMID- 27661189 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Jo Barr, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX (Fax 081-423 3867). PMID- 27661191 TI - Special quasirandom structures for perovskite solid solutions. AB - Special quasirandom structures (SQS) are presently generated for disordered (A'1 x [Formula: see text] x )BX3 and A(B'1-x [Formula: see text] x )X3 perovskite solid solutions, with x = 1/2 as well as 1/3 and 2/3. These SQS configurations are obtained by imposing that the so-called Cowley parameters are as close to zero as possible for the three nearest neighboring shells. Moreover, these SQS configurations are slightly larger in size than those available in the literature for x = 1/2, mostly because of the current capabilities of atomistic techniques. They are used here within effective Hamiltonian schemes to predict various properties, which are then compared to those associated with large random supercells, in a variety of compounds, namely (Ba1-x Sr x )TiO3, Pb(Zr1-x Ti x )O3, Pb(Sc0.5Nb0.5)O3, Ba(Zr1-x Ti x )O3, Pb(Mg1/3Nb2/3)O3 and (Bi1-x Nd x )FeO3. It is found that these SQS configurations can reproduce many properties of large random supercells of most of these disordered perovskite alloys, below some finite material-dependent temperature. Examples of these properties are electrical polarization, anti-phase and in-phase octahedral tiltings, antipolar motions, antiferromagnetism, strain, piezoelectric coefficients, dielectric response, specific heat and even the formation of polar nanoregions (PNRs) in some relaxors. Some limitations of these SQS configurations are also pointed out and explained. PMID- 27661193 TI - Determining Number Concentrations and Diameters of Polystyrene Particles by Measuring the Effective Refractive Index of Colloids Using Surface Plasmon Resonance. AB - The capabilities of surface plasmon resonance (SPR) for characterization of colloidal particles were evaluated for 100, 300, and 460 nm nominal diameter polystyrene (PS) latexes. First the accuracy of measuring the effective refractive index (neff) of turbid colloids using SPR was quantified. It was concluded that for submicrometer sized PS particles the accuracy is limited by the reproducibility between replicate injections of samples. An SPR method was developed for obtaining the particle mean diameter (dpart) and the particle number concentration (cp) by fitting the measured neff of polystyrene (PS) colloids diluted in series with theoretical values calculated using the coherent scattering theory (CST). The dpart and cp determined using SPR agreed with reference values obtained from size distributions measured by scanning electron microscopy (SEM), and the mass concentrations stated by the manufacturer. The 100 nm particles adsorbed on the sensing surface, which hampered the analysis. Once the adsorption problem has been overcome, the developed SPR method has potential to become a versatile tool for characterization of colloidal particles. In particular, SPR could form the basis of rapid and accurate methods for measuring the cp of submicrometer particles in dispersion. PMID- 27661194 TI - Correction to Insights from Fragment Hit Binding Assays by Molecular Simulations. PMID- 27661192 TI - Intranasal oxytocin dampens cue-elicited cigarette craving in daily smokers: a pilot study. AB - Despite moderate success with pharmacological and behavioral treatments, smoking relapse rates remain high, and many smokers report that smoking cues lead to relapse. Therefore, treatments that target cue reactivity are needed. One candidate for reducing craving is the neuropeptide oxytocin (OT). Here, we investigated the effects of intranasal OT on two types of craving for cigarettes: craving following overnight abstinence and craving elicited by smoking-related cues. In this within-subject, placebo-controlled pilot study, smokers (N=17) abstained from smoking for 12 h before attending two sessions randomized to intranasal OT or placebo (i.e. saline nasal spray). On each session, participants received two doses of OT (20 IU) or placebo at 1-h intervals, and rated craving before and after each dose. Spontaneous cigarette craving was assessed after the first spray, and cue-elicited craving was assessed following the second spray. OT did not reduce levels of spontaneous craving after the first spray, but significantly dampened cue-induced smoking craving. These results provide preliminary evidence that OT can reduce cue-induced smoking craving in smokers. These findings provide an important link between preclinical and clinical studies aimed at examining the effectiveness of OT as a novel treatment for drug craving. PMID- 27661195 TI - Management of Patellofemoral Arthritis: From Cartilage Restoration to Arthroplasty. AB - The management of patellofemoral cartilage lesions is controversial and should begin with a comprehensive nonsurgical treatment plan. Patients with patellofemoral cartilage lesions in whom nonsurgical treatment fails may be candidates for surgical treatment. Surgical treatment strategies for the management of patellofemoral cartilage lesions are guided by the size, quality, and location of the defect. Recent advancements in cartilage restoration and arthroplasty techniques as well as appropriate patient selection and meticulous surgical technique have resulted in promising outcomes in patients with patellofemoral cartilage lesions who undergo surgical treatment. PMID- 27661197 TI - Chronic Headaches After a Concussion in an Obese 16-Year-Old Girl. AB - CASE: Jennifer is a 16-year-old Latina girl who is new to your practice. During her first well visit, she mentions that she has had daily headaches for 2 years. They began after sustaining a concussion in a car accident. Typically, her headaches are bilateral and "squeezing"; they occur in the afternoons and last for a few hours. Her concussion also resulted in depressed mood, which has improved over time.When you ask if her headaches have changed recently, she says that they have been worse for the last few days. The quality and severity are unchanged; however, they now occur first thing in the morning, are worse when supine, and no longer remit. In the last 2 days, she has developed new-onset blurry vision, nausea, dizziness, photophobia, and sonophobia. Although she previously experienced sadness with her concussion, she now feels irritable. She has never used tobacco, alcohol, or drugs, and she takes no medications.On examination, her body mass index is above the 99th percentile. You note mild papilledema bilaterally. She has no focal neurological deficits. The remainder of her examination is normal.You send her to an emergency department. Her head computed tomography is normal. A lumbar puncture demonstrates an opening pressure of 32 cm H2O; she feels relief after the procedure. She is admitted with a diagnosis of benign intracranial hypertension and is started on acetazolamide. What is the differential diagnosis of chronic headaches in an obese adolescent? How should a busy community pediatrician manage Jennifer acutely? What follow-up care should Jennifer receive? PMID- 27661198 TI - Changes in brain activation induced by visual stimulus during and after propofol conscious sedation: a functional MRI study. AB - Conscious sedation with propofol sometimes causes amnesia while keeping the patient awake. However, it remains unknown how propofol compromises the memory function. Therefore, we investigated the changes in brain activation induced by visual stimulation during and after conscious sedation with propofol using serial functional MRI. Healthy volunteers received a target-controlled infusion of propofol, and underwent functional MRI scans with a block-design paradigm of visual stimulus before, during, and after conscious sedation. Random-effect model analyses were performed using Statistical Parametric Mapping software. Among the areas showing significant activation in response to the visual stimulus, the visual cortex and fusiform gyrus were significantly suppressed in the sedation session and tended to recover in the early-recovery session of ~20 min (P<0.001, uncorrected). In contrast, decreased activations of the hippocampus, thalamus, inferior frontal cortex (ventrolateral prefrontal cortex), and cerebellum were maintained during the sedation and early-recovery sessions (P<0.001, uncorrected) and were recovered in the late-recovery session of ~40 min. Temporal changes in the signals from these areas varied in a manner comparable to that described by the random-effect model analysis (P<0.05, corrected). In conclusion, conscious sedation with propofol may cause prolonged suppression of the activation of memory-related structures, such as the hippocampus, during the early-recovery period, which may lead to transient amnesia. PMID- 27661196 TI - Phototriggered Drug Delivery Using Inorganic Nanomaterials. AB - Light has many desirable properties as the stimulus for triggerable drug delivery systems. Inorganic nanomaterials are often key components in transducing light into drug delivery events. The nature of the light and the inorganic materials can affect the efficacy and safety of the drug delivery system. PMID- 27661200 TI - In Situ High Temperature Atomic Level Studies of Large Closed Grain Boundary Loops in Graphene. AB - We use an in situ heating holder within an aberration corrected transmission electron microscope (AC-TEM) to study the structure and dynamics of large closed grain boundary (GB) loops in graphene at the atomic level. Temperatures up to 800 degrees C are used to accelerate dynamic evolution of the defect clusters, increasing bond rotation and atomic addition/loss. Our results show that the large closed GB loops relax under electron beam irradiation into several isolated dislocations far apart from each other. Line defects composed of several adjacent excess-atom clusters can be found during the reconfiguration process. Dislocation ejection from the closed GB loops are seen in real time and are shown to help the reduction in loop size. These results show detailed information about the stability and behavior of large GB loops in 2D materials that have importance in the high temperature processing of these materials. PMID- 27661199 TI - Mechanism of the Primary Charge Transfer Reaction in the Cytochrome bc1 Complex. AB - The bc1 complex is a critical enzyme for the ATP production in photosynthesis and cellular respiration. Its biochemical function relies on the so-called Q-cycle, which is well established and operates via quinol substrates that bind inside the protein complex. Despite decades of research, the quinol-protein interaction, which initiates the Q-cycle, has not yet been completely described. Furthermore, the initial charge transfer reactions of the Q-cycle lack a physical description. The present investigation utilizes classical molecular dynamics simulations in tandem with quantum density functional theory calculations, to provide a complete and consistent quantitative description of the primary events that occur within the bc1 complex upon quinol binding. In particular, the electron and proton transfer reactions that trigger the Q-cycle in the bc1 complex from Rhodobacter capsulatus are studied. The coupled nature of these charge transfer reactions was revealed by obtaining the transition energy path connecting configurations of the Qo-site prior and after the transfers. The analysis of orbitals and partial charge distribution of the different states of the Qo-site has further supported the conclusion. Finally, key structural elements of the bc1 complex that trigger the charge transfer reactions were established, manifesting the importance of the environment in the process, which is furthermore evidenced by free energy calculations. PMID- 27661201 TI - The Settings, Pros and Cons of the New Surgical Robot da Vinci Xi System for Transoral Robotic Surgery (TORS): A Comparison With the Popular da Vinci Si System. AB - The da Vinci system (da Vinci Surgical System; Intuitive Surgical Inc.) has rapidly developed in several years from the S system to the Si system and now the Xi System. To investigate the surgical feasibility and to provide workflow guidance for the newly released system, we used the new da Vinci Xi system for transoral robotic surgery (TORS) on a cadaveric specimen. Bilateral supraglottic partial laryngectomy, hypopharyngectomy, lateral oropharyngectomy, and base of the tongue resection were serially performed in search of the optimal procedures with the new system. The new surgical robotic system has been upgraded in all respects. The telescope and camera were incorporated into one system, with a digital end-mounted camera. Overhead boom rotation allows multiquadrant access without axis limitation, the arms are now thinner and longer with grabbing movements for easy adjustments. The patient clearance button dramatically reduces external collisions. The new surgical robotic system has been optimized for improved anatomic access, with better-equipped appurtenances. This cadaveric study of TORS offers guidance on the best protocol for surgical workflow with the new Xi system leading to improvements in the functional results of TORS. PMID- 27661202 TI - Cholecystostomy Treatment in an ICU Population: Complications and Risks. AB - BACKGROUND: Percutaneous cholecystostomy tube placement has widely been used as an alternative treatment to cholecystectomy, especially in advanced disease or critically ill patients. Reported postprocedural complication rates have varied significantly over the last decade. The goal of this study is to evaluate the safety of percutaneous cholecystostomy tube treatment in critically ill patients. STUDY DESIGN: We performed a retrospective chart analysis of 96 critically ill patients who underwent cholecystostomy tube placement during an intensive care unit (ICU) stay between 2005 and 2010 in a tertiary care center in central Massachusetts. Complications within 72 hours of cholecystostomy tube placement and any morbidity or mortality relating to presence of cholecystostomy tube were considered. RESULTS: A total of 65 male and 31 female patients with a mean age of 67.4 years underwent percutaneous cholecystostomy tube placement during an ICU stay. Sixty-six patients experienced a total of 121 complications, resulting in an overall complication rate of 69%. Fifty-four of these complications resulted from the actual procedure or the presence of the cholecystostomy tube; the other 67 complications occurred within 72 hours of the cholecystostomy procedure. Ten patients died. Tube dislodgment was the most common complication with a total of 34 episodes. CONCLUSIONS: Cholecystostomy tube placement is associated with frequent complications, the most common of which is tube dislodgment. Severe complications may contribute to serious morbidity and death in an ICU population. Complication rates may be underreported in the medical literature. The potential impact of cholecystostomy tube placement in critically ill patients should not be underestimated. PMID- 27661203 TI - Laparoscopic Treatment of Presinusoidal Schistosomal Portal Hypertension Associated With Postoperative Endoscopic Treatment: Results of a New Approach. AB - AIM: To propose a laparoscopic treatment for schistosomal portal hypertension. METHODS: Ten patients with schistosomiasis and portal hypertension, with previous gastrointestinal hemorrhage from esophageal varices rupture, were evaluated. Patients were subjected to a laparoscopic procedure, with ligature of splenic artery and left gastric vein. Upper gastrointestinal endoscopy was performed on the 30th postoperative day, when esophageal varices diameter was measured and band ligature performed. During follow-up, other endoscopic procedures were performed according to endoscopy findings. RESULTS: There was no operative mortality. One patient had a postoperative splenic infarction that was conservatively treated. Mean hospitalization time was 5 days. During endoscopy 30 days after surgery, a decrease in variceal diameters was observed in 6 patients. During follow-up (mean 84 mo), after endoscopic therapy 8 patients had eradicated varices, but 4 presented with recurrence. Considering the late postoperative evaluation, all patients had a decrease in variceal diameters. A mean of 3.8 endoscopic banding sessions were performed per patient. Two patients presented bleeding recurrence; one had a minor bleeding episode and the other had 2 episodes of bleeding varices requiring blood transfusion. In both patients, bleeding was controlled with endoscopic therapy. No late mortality was observed. CONCLUSIONS: Laparoscopic ligature of the splenic artery and the left gastric vein is a promising and less-invasive method for the treatment of schistosomal portal hypertension. PMID- 27661204 TI - Gastrostomy Placement in Children: Percutaneous Endoscopic Gastrostomy or Laparoscopic Gastrostomy? AB - The aim of this study is to compare the outcomes and the complications between the 2 most adopted procedures for gastrostomy placement: percutaneous endoscopic gastrostomy (PEG) and laparoscopic gastrostomy (LG) in children. We present our study on 69 patients (male: 46/female: 23): group 1 (37 patients, 54%) undergoing PEG, group 2 (32 patients, 46%) undergoing LG. A total of 5 major complications were observed all in the PEG group (13.5%), no major complication was observed in the LG group (P-value<0.05). A total of 12 minor complications were observed: 4 occurred in the PEG group (10.8%) and 8 (25%) in the laparoscopic gastrostmoy group, not statistically relevant. We suggest that the LG should be considered the preferred technique for gastrostomy placement in pediatric patients, particularly in newborns, children with significant skeletal malformations, and patients who underwent previous abdominal surgery. PMID- 27661205 TI - A 10-Year Review of Surgical Management of Complicated Peptic Ulcer Disease From a Single Center: Is Laparoscopic Approach the Future? AB - INTRODUCTION: The discovery of Helicobacter pylori (H. pylori) as the culprit in peptic ulcer disease (PUD) has revolutionized its management. Despite the presence of effective drug treatments and an increased understanding of its etiology, the percentage of patients who require emergent surgery for complicated disease remains constant at 7% of hospitalized patients. This study aims at reviewing the incidence of complicated PUD and analyze changes in surgical management. PATIENTS AND METHODS: From January 2002 to September 2012, records of all patients with a clinical or radiologic diagnosis of perforated PUD were evaluated. Short-term and long-term results were assessed with regard to type of surgical intervention. The primary end point was adverse events. Other end points were length of hospital stay, complications, and deaths. RESULTS: Included were 400 patients with a median age of 56 years (range, 17 to 89 y). Of these, males made up 70% (n=280), were older and had more comorbidities. Majority of perforations were located in the prepyloric region (80%) and duodenal bulb (20%). Nonsteroidal anti-inflammatory drug alone was involved in 50% of cases and in combination with H. pylori in 84%. H. pylori alone occurred in 40% of cases.Laparoscopic treatment was performed in 48 patients (12%) who remained hemodynamically stable. In the remaining 88% of patients, open approach was used. Simple closure with omentoplasty was performed in 98% and in 2%; definitive anti ulcer procedure was performed. Major complications occurred in 6% with an overall 30-day mortality rate of 2%. Most postoperative morbidity occurred after open approach. One patient who had laparoscopic repair died of other causes unrelated to the gastroduodenal perforation. Among the laparoscopic group, mean hospital stay was 4 days (range, 3 to 7 d), compared with 6 days (5 to 14 d) after open approach. CONCLUSIONS: Although the incidence of PUD is decreasing, it appears that among our patients, the incidence of complication is rising. Laparoscopic approach offers an alternative treatment with less pain, shorter hospital stay, and improved complications rate. PMID- 27661206 TI - Gastrointestinal Stromal Tumor of Stomach: A Gentle Enemy of the Surgeon. Our Experience in Confronting the Disease. AB - BACKGROUND: Surgical resection is considered to be the best treatment for gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the gastrointestinal tract. Tumor size, mitotic rate, and anatomic locations are directly related to the potential malignancy, surgical approach, oncological treatment, and recurrence rate. MATERIALS AND METHODS: This was a retrospective study of 40 patients who underwent surgical resection of histologically or immunohistochemistry-proven GIST of the stomach at the Rabin and Kaplan Medical Center between 2004 and 2013. Tumor size, location, margin status, pathologic characteristics, surgical approach, surgical outcome, and long-term follow-up were analyzed from hospital records. RESULTS: The most common presentation was upper gastrointestinal bleeding (40%), although 30% of cases were asymptomatic. A laparoscopic approach was the preferred technique whenever feasible; 85% of tumors were localized in the proximal stomach, with a median size of 5.6 cm. Most of the resected tumors revealed a low mitotic rate and thus had low-moderate risks of malignancy. All tumors were completely resected with free surgical margins. The median follow-up period was 40 months with 93% disease-free survival. CONCLUSIONS: Gastric GIST is a snake in the grass and its diagnosis is often incidental to endoscopy and computed tomographic scan. The most important technical point is to avoid tumor rupture during removal. PMID- 27661207 TI - Brain networks stimulation in dementia: insights from functional imaging. AB - PURPOSE OF REVIEW: Noninvasive brain stimulation (NIBS) is increasingly used in the field of dementia as a therapeutic option; however, evidence of clinical efficacy is limited, and the mechanism of action remains unknown. This review summarizes how functional imaging could contribute to the design of targeted and effective NIBS interventions for dementia. RECENT FINDINGS: Resting-state functional magnetic resonance imaging (fMRI) has largely contributed to understanding brain dysfunction in dementia by identifying disease-specific networks. Resting-state fMRI might inform on a number of factors critical for the conduction of effective NIBS trials, such as definition of stimulation paradigms and choice of the stimulation target. In addition, fMRI may contribute to the understanding of the mechanisms of action of NIBS, and provide a tool to monitor treatment efficacy. SUMMARY: Functional imaging is a promising approach for the development of hypothesis-driven, targeted stimulation approaches in the field of dementia. PMID- 27661208 TI - Leptomeningeal metastases of solid cancer. AB - PURPOSE OF REVIEW: To review recent original data on leptomeningeal metastases in patients with solid cancer. RECENT FINDINGS: Lung and breast cancer as well as melanoma remain the most common primaries. Advanced cytological methods and targeted sequencing for candidate tumor-specific mutations may improve the sensitivity of cerebrospinal fluid diagnostics in leptomeningeal metastases. Targeted treatments like epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer, anti-human epidermal growth factor receptor-2 treatments for breast cancer or B-rapidly accelerated fibrosarcoma targeted or immunotherapy for melanoma have an emerging role in the management of this condition. SUMMARY: Novel diagnostic approaches and the introduction of targeted agents may improve the clinical management of patients with leptomeningeal metastases from solid cancers. PMID- 27661209 TI - Structure-Property Relationships in alpha-, beta'-, and gamma-Modifications of Mn3(PO4)2. AB - The manganese orthophosphate, Mn3(PO4)2, is characterized by the rich variety of polymorphous modifications, alpha-, beta'-, and gamma-phases, crystallized in monoclinic P21/c (P21/n) space group type with unit cell volume ratios of 2:6:1. The crystal structures of these phases are constituted by three-dimensional framework of corner- and edge-sharing [MnO5] and [MnO6] polyhedra strengthened by [PO4] tetrahedra. All compounds experience long-range antiferromagnetic order at Neel temperature TN = 21.9 K (alpha-phase), 12.3 K (beta'-phase), and 13.3 K (gamma-phase). Additionally, second magnetic phase transition takes place at T* = 10.3 K in beta'-phase. The magnetization curves of alpha- and beta'-modifications evidence spin-floplike features at B = 1.9 and 3.7 T, while the gamma-Mn3(PO4)2 stands out for an extended one-third magnetization plateau stabilized in the range of magnetic field B = 7.5-23.5 T. The first-principles calculations define the main paths of superexchange interaction between Mn spins in these polymorphs. The spin model for alpha-phase is found to be characterized by collection of uniform and alternating chains, which are coupled in all three directions. The strongest magnetic exchange interaction in gamma-phase emphasizes the trimer units, which make chains that are in turn weakly coupled to each other. The spin model of beta'-phase turns out to be more complex compared to alpha- or gamma phase. It shows complex chain structures involving exchange interactions between Mn2 (Mn2', Mn2") and Mn3 (Mn3', Mn3"). These chains interact through exchanges involving Mn1 (Mn1', Mn1") spins. PMID- 27661210 TI - Neuroleptics in the management of delirium in patients with advanced cancer. AB - PURPOSE OF REVIEW: Delirium is the most common and distressing neuropsychiatric syndrome in cancer patients. Few evidence-based treatment options are available due to the paucity of high quality of studies. In this review, we shall examine the literature on the use of neuroleptics to treat delirium in patients with advanced cancer. Specifically, we will discuss the randomized controlled trials that examined neuroleptics in the front line setting, and studies that explore second-line options for patients with persistent agitation. RECENT FINDINGS: Contemporary management of delirium includes identification and management of any potentially reversible causes, coupled with nonpharmacological approaches. For patients who do not respond adequately to these measures, pharmacologic measures may be required. Haloperidol is often recommended as the first-line treatment option, and other neuroleptics such as olanzapine, risperidone, and quetiapine represent potential alternatives. For patients with persistent delirium despite first-line neuroleptics, the treatment strategies include escalating the dose of the same neuroleptic, rotation to another neuroleptic, or combination therapy (i.e., the addition of a second neuroleptic or other agent). We will discuss the advantages and disadvantages of each approach, and the available evidence to support each strategy. SUMMARY: Adequately powered, randomized trials involving proper control interventions are urgently needed to define the optimal treatment strategies for delirium in the oncology setting. PMID- 27661211 TI - Knowledge and Comfort With Pessary Use: A Survey of US Obstetrics and Gynecology Residents. AB - OBJECTIVE: This study aimed to determine factors associated with perceived comfort with pessary management among obstetrics and gynecology (OB/GYN) residents in the United States. METHODS: A 31-item anonymous electronic survey regarding experience with, attitudes toward, and comfort with pessary management was distributed to US OB/GYN residents in all postgraduate years (PGYs). Demographic and program-specific data on pessary education were collected. Descriptive statistical analyses were performed. Single-predictor logistic regression analysis, followed by analysis of a multivariable model that included significant single predictors, was performed to determine factors associated with residents' perception of comfort. Results were stratified for junior (PGYs 1, 2), senior (PGYs 3, 4), and chief (PGY4) residents. RESULTS: Four hundred seventy eight completed surveys were returned and analyzed. Mean age of respondents was 29.5 (+/-2.56) years. Training levels were distributed evenly (PGY1, 25%; PGY2, 28%; PGY3, 25%; PGY4, 22%). Twenty-eight percent had a urogynecology fellowship in the department. Factors associated with comfort were similar for all training levels and included working with advanced practitioners, a formal urogynecology rotation, experience with pessary fitting, and receiving formal pessary-specific didactics (P < 0.001). PGY4s also benefitted from a formal urogynecology rotation. Factors that did not improve comfort were having a urogynecology fellowship and receiving general didactics on prolapse and incontinence. CONCLUSIONS: Gaining outpatient experience, especially with pessary fitting, along with formal didactics specific to pessary fitting and management may improve resident' confidence with pessary use. PMID- 27661212 TI - Pelvic Organ Prolapse Stage and the Relationship to Genital Hiatus and Perineal Body Measurements. AB - OBJECTIVES: This study aimed to describe the relationship between genital hiatus (GH) and perineal body (PB) measurements with increasing pelvic organ prolapse (POP) stage in a large cohort of women referred to Urogynecology clinic for pelvic floor disorders. METHODS: Retrospective chart review of all new patients seen in an academic Urogynecology clinic between January 2007 and September 2011 was performed. Data were extracted from a standardized intake form. All patients underwent a Pelvic Organ Prolapse Quantification (POPQ) examination. Descriptive statistics compared the study population. Analysis of variance was used to compare GH and PB measurements by prolapse stage. Fisher least significant differences were used for post hoc comparisons of means between prolapse stages. Pearson correlations were used to evaluate the associations between GH and PB measurements and patient characteristics. RESULTS: A total of 1595 women with POPQ examinations comprised the study population. The mean age was 55.3 +/- 14.8 years with a body mass index of 30.3 +/- 7.6 kg/m, most women were parous (90%), 40% were Hispanic, and 33% had undergone prior hysterectomy for indications exclusive of POP. Women with any prior prolapse repair were excluded, 6.5% had a prior incontinence procedure. Perineal body measurements were slightly larger for stage 2 POP, but overall did not vary across other prolapse stages (all P > 0.05). In contrast, GH measurements increased through stage 3 POP, GH measurements decreased for stage 4 POP. CONCLUSIONS: Mean PB measurements did not demonstrate large changes over prolapse stage, whereas GH measurements increased through stage 3 POP. Genital hiatus serves as an important marker for underlying pelvic muscle damage. PMID- 27661213 TI - Defining Expertise in Gynecologic Surgery: Perspectives of Expert Gynecologic Surgeons. AB - OBJECTIVE: The aim of this study was to describe how professional expertise is defined and understood among gynecologic surgeons and what experiential factors contribute to that understanding. METHODS: Semistructured interviews with 16 experts in Female Pelvic Medicine and Reconstructive Surgery were conducted to identify how expertise in their field is defined, recognized, and assessed. Independent thematic analysis of the interview transcripts was performed by each member of the research team and then distilled and synthesized into convergent themes. RESULTS: Experts described surgical expertise as difficult to define but with several dominant themes including knowledge, technical skills, clinical experience, adaptability, continuous learning, communication, and professional recognition. Expertise requires judgment in applying technical skills to meet each patient's specific needs. Experts described unique ways of seeing and thinking during surgery, characterized by spatial awareness of relevant anatomy, temporal awareness of future changes, and rapidly adaptive application of their skills enabling them to do difficult tasks with fluidity, making the tasks seem easy to observers. These expert surgeons acknowledged that achieving expertise requires hard work and maintaining expertise requires continuous learning, highlighted by challenge seeking to do the most difficult tasks in their field. They also noted the importance of effective communication of their knowledge to others, which contributes to their perception as experts by colleagues in the field. CONCLUSIONS: Surgical expertise is a complex phenomenon with several meaningful themes. Understanding the authentic nature of surgical expertise can be used to support the development of competencies and the effective mentoring of promising surgical trainees to achieve surgical expertise. PMID- 27661214 TI - Titanium Surgical Tacks: Are They Safe? Do They Work? AB - OBJECTIVES: Minimally invasive approaches to sacrocolpopexy have transformed it into a primary procedure for treatment of pelvic organ prolapse. Certain modifications are commonly used to facilitate the laparoscopic approach, but have not yet been widely studied. In this study, we investigated the efficacy and safety of titanium surgical tacks for the attachment of mesh to the anterior longitudinal ligament in laparoscopic sacrocolpopexy. METHODS: This retrospective cohort study involved all patients within 1 health care system who underwent laparoscopic sacrocolpopexy between January 2009 and December 2012. Each medical record was reviewed and abstracted. RESULTS: Of the 231 patients included in our study, 190 (82%) had titanium surgical tacks, and 41 (18%) had suture for mesh attachment to the anterior longitudinal ligament. The demographics of the 2 subgroups as well as concomitantly performed procedures were comparable. There was no significant difference found between the 2 cohorts in regards to operative time, estimated blood loss, complication rates, rate of recurrent pelvic organ prolapse symptoms or the rate of reoperation for pelvic organ prolapse. CONCLUSIONS: Surgical tacks are a safe alternative to suture for the attachment of mesh to the anterior longitudinal ligament in laparoscopic sacrocolpopexy. Although we saw no advantage to using tacks over suture, tacking the mesh to the anterior longitudinal ligament may make the laparoscopic approach more accessible to a wider range of gynecologic surgeons. Further studies about the long-term impact of surgical tacks on bone and disk disease are needed. PMID- 27661215 TI - Evaluation of the Cost of Comprehensive Outpatient Therapies in Patients with Malignant Brain Tumors. AB - OBJECTIVE: The aim of this study was to compare the cost of comprehensive outpatient therapy (day rehabilitation) in individuals with malignant brain tumors to those with stroke and traumatic brain injury. DESIGN: This was a prospective, nonrandomized, longitudinal study of 49 consecutive adults with malignant brain tumors enrolled in the 6 day rehabilitation sites of 1 institution over 35 months. The control group was composed of 50 patients with brain injury and 50 patients with stroke, who were also enrolled in the day rehabilitation program during the same period. A comparison was made of the total Medicare cost and the cost per day of day rehabilitation in patients with malignant brain tumors compared with the control group. RESULTS: The patients with malignant brain tumors had lower total cost and cost per day than did the combined traumatic brain injury and stroke group during day rehabilitation (F2,143 = 3.056 [P = 0.05] and F2,142 = 5.046 [P = 0.008], respectively). CONCLUSIONS: The cost of comprehensive outpatient rehabilitation in patients with malignant brain tumors is less expensive than that of patients with traumatic brain injury or stroke, which are neurological diagnoses commonly seen in day rehabilitation. This study shows that cost should not be a barrier to providing outpatient therapies to this patient population. PMID- 27661218 TI - The Sunken Skull. PMID- 27661219 TI - Invited Commentary: Past History, and Future Directions. PMID- 27661220 TI - Advances in the field of proprotein convertase subtilisin kexin type 9 inhibitors. AB - PURPOSE OF REVIEW: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are promising therapies that inhibit the degradation of low-density lipoprotein (LDL) receptors in the hepatocyte and thus increase LDL cholesterol (LDL-C) uptake from the blood. This review summarizes main findings in the field of PCSK9 inhibitors, from basic mechanism to clinical studies, and aims to provide a contemporary and practical overview of the clinical implication and future directions with PCSK9 inhibitors. RECENT FINDINGS: Monoclonal antibodies that inhibit PCSK9 reduce LDL-C levels by 40-70% across a wide range of patients with various LDL-C levels, and with different lipid-lowering regimens. These agents significantly reduce apolipoprotein B and lipoprotein (a), may have a potential role in plaque stabilization in acute coronary syndromes, and are safe and tolerable, even among statin-intolerant patients. Preliminary data with evolocumab and alirocumab demonstrate the potential reduction of cardiovascular (CV) events. These PCSK9 inhibitors were recently approved for clinical use, and recommended in the 2016 American College of Cardiology expert consensus document for nonstatin therapy for LDL-C lowering. SUMMARY: PCSK9 inhibitors are novel promising therapies to reduce LDL-C. Ongoing phase 3 clinical trials with more than 70 000 high-risk patients will examine their safety and efficacy in reducing cardiovascular disease. PMID- 27661221 TI - Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates. AB - The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity. Yet, these models are far from satisfactory due to extensive species differences and because hepatocytes in 2D cultures rapidly dedifferentiate resulting in the loss of their hepatic phenotype and functionality. With the increasing comprehension that 3D cell culture systems more accurately reflect in vivo physiology, in the recent decade more and more research has focused on the development and optimization of various 3D culture strategies in an attempt to preserve liver properties in vitro. In this contribution, we critically review these developments, which have resulted in an arsenal of different static and perfused 3D models. These systems include sandwich-cultured hepatocytes, spheroid culture platforms, and various microfluidic liver or multiorgan biochips. Importantly, in many of these models hepatocytes maintain their phenotype for prolonged times, which allows probing the potential of newly developed chemical entities to cause chronic hepatotoxicity. Moreover, some platforms permit the investigation of drug action in specific genetic backgrounds or diseased hepatocytes, thereby significantly expanding the repertoire of tools to detect drug-induced liver injuries. It is concluded that the development of 3D liver models has hitherto been fruitful and that systems are now at hand whose sensitivity and specificity in detecting hepatotoxicity are superior to those of classical 2D culture systems. For the future, we highlight the need to develop more integrated coculture model systems to emulate immunotoxicities that arise due to complex interactions between hepatocytes and immune cells. PMID- 27661222 TI - Talking to Each Other. PMID- 27661223 TI - The TIDieR Checklist Will Benefit the Physical Therapy Profession. PMID- 27661224 TI - Outcomes for Students Receiving School-Based Physical Therapy as Measured by the School Function Assessment. AB - PURPOSE: To describe School Function Assessment (SFA) outcomes after 6 months of school-based physical therapy and the effects of age and gross motor function on outcomes. METHODS: Within 28 states, 109 physical therapists and 296 of their students with disabilities, ages 5 to 12 years, participated. After training, therapists completed 10 SFA scales on students near the beginning and end of the school year. RESULTS: Criterion scores for many students remained stable (46% 59%) or improved (37%-51%) with the most students improving in Participation and Maintaining/Changing Positions. Students aged 5 to 7 years showed greater change than 8- to 12-year-olds on 5 scales. Students with higher gross motor function (Gross Motor Function Classification System levels I vs IV/V and II/III vs IV/V) showed greater change on 9 scales. CONCLUSIONS: Positive SFA change was recorded in students receiving school-based physical therapy; however, the SFA is less sensitive for older students and those with lower functional movement. PMID- 27661225 TI - Commentary on "Outcomes for Students Receiving School-Based Physical Therapy as Measured by the School Function Assessment". PMID- 27661226 TI - The Influence of Position on Leg Movements and Kicks in Older Infants With Spina Bifida. AB - PURPOSE: The purpose of this study was to describe the frequency with which infants with lumbar or sacral spina bifida (SB) move their legs or kick when they are 7 months and older while in the supine position, seated in a conventional infant seat (CS), and seated in a specially designed infant seat (SDIS). METHODS: The spontaneous leg movements of 9 infants with lumbar or sacral SB were videotaped once per month for 4 months in each position. RESULTS: Infants generated significantly more leg movements when seated in the SDIS than in the CS and significantly more kicks in the SDIS than in the other 2 positions. CONCLUSIONS: The movement context influences the ability of older infants with SB to move their legs and to kick. PMID- 27661227 TI - Commentary on "The Influence of Position on the Leg Movements and Kicks in Older Infants With Spina Bifida". PMID- 27661228 TI - Commentary on "Relationship Between Abdominal Adiposity and Exercise Tolerance in Children With Obesity". PMID- 27661229 TI - Commentary on "Influence of External Visual Focus on Gait in Children With Bilateral Cerebral Palsy". PMID- 27661230 TI - Reliability and Responsiveness of the Timed Up and Go Test in Children With Cerebral Palsy. AB - PURPOSE: The purpose of this study was to determine the absolute reliability and responsiveness of the Timed Up and Go (TUG) test, as measured using minimal detectable change (MDC) and minimal clinical important difference (MCID) values. METHODS: Prospective observational study of children aged 3 to 10 years with cerebral palsy (CP) in Gross Motor Function Classification System levels I-III who completed the TUG test. Minimal detectable change estimates were calculated using baseline data. MCID estimates for each Gross Motor Function Classification System (GMFCS) level were calculated using distribution- and anchor-based methods. RESULTS: Minimal detectable change values ranged from 1.40 to 8.74 seconds and MCID estimates ranged from 0.22 to 5.31 seconds. CONCLUSIONS: The TUG test is a reliable and responsive measure of balance and mobility for children with CP between 3 and 10 years of age in GMFCS levels I-III. Study results support improved use of the TUG test in clinical and research settings by providing reliability values and estimates of meaningful change. VIDEO ABSTRACT: For more insights from the authors, see Supplemental Digital Content 1, available at http://links.lww.com/PPT/A117. PMID- 27661231 TI - Commentary on "Reliability and Responsiveness of the Timed Up and Go Test in Children With Cerebral Palsy". PMID- 27661232 TI - A Modified Version of the Timed Up and Go Test for Children Who Are Preschoolers. AB - PURPOSE: This study investigated factors predicting the Timed Up and Go (TUG) test in children who are preschoolers, using a modified protocol of the TUG. METHOD: This was a cross-sectional study of children 3 to 5 years old (n = 192). Regression analysis identified predictive factors for TUG performances. Differences in mean values (standard deviation) were calculated for each age group. RESULTS: The results of 172 children were analyzed. Age and ethnicity were predictive of TUG performance (R = 0.280). Children who are preschoolers with Flemish ethnicity need less time to perform the TUG than their peers with another ethnicity (P < .05), but this difference is not significant for the age groups. The TUG performance differs significantly among all age groups (P < .05). CONCLUSIONS: A modified protocol for the TUG, which is sensitive to age-related changes in dynamic balance control, is proposed for children who are preschoolers. PMID- 27661233 TI - Commentary on "A Modified Version of the Timed Up and Go Test for Children Who Are Preschoolers". PMID- 27661234 TI - Commentary on "Development and Initial Validation of the Pediatric Neuromuscular Recovery Scale". PMID- 27661235 TI - Validation of Accelerometer Cut-Points in Children With Cerebral Palsy Aged 4 to 5 Years. AB - PURPOSE: To derive and validate triaxial accelerometer cut-points in children with cerebral palsy (CP) and compare these with previously established cut-points in children with typical development. METHODS: Eighty-four children with CP aged 4 to 5 years wore the ActiGraph during a play-based gross motor function measure assessment that was video-taped for direct observation. Receiver operating characteristic and Bland-Altman plots were used for analyses. RESULTS: The ActiGraph had good classification accuracy in Gross Motor Function Classification System (GMFCS) levels III and V and fair classification accuracy in GMFCS levels I, II, and IV. These results support the use of the previously established cut points for sedentary time of 820 counts per minute in children with CP aged 4 to 5 years across all functional abilities. CONCLUSIONS: The cut-point provides an objective measure of sedentary and active time in children with CP. The cut-point is applicable to group data but not for individual children. PMID- 27661236 TI - Commentary on "Validation of Accelerometer Cut-Points in Children With Cerebral Palsy Aged 4 to 5 Years". PMID- 27661237 TI - Layout for Assessing Dynamic Posture: Development, Validation, and Reproducibility. AB - PURPOSE: To determine the psychometric properties of the layout for assessing dynamic posture (LADy). METHODS: The study was divided into 2 phases: (1) development of the instrument and (2) determination of validity and reproducibility. The LADy was designed to evaluate the position adopted in 9 dynamic postures. RESULTS: The results confirmed the validity and reproducibility of the instrument. From a total of 51 criteria assessing 9 postures, 1 was rejected. The reproducibility for each of the criteria was classified as moderate to excellent. CONCLUSIONS: The LADy constitutes a valid and reproducible instrument for the evaluation of dynamic postures in children 11 to 17 years old. It is low cost and applicable in the school environment. PMID- 27661238 TI - Commentary on "Layout for Assessing Dynamic Posture: Development, Validation, and Reproducibility". PMID- 27661239 TI - Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects. AB - PURPOSE: To compare changes in motor development from 1 to 5 years of age among 18 children with hypoplastic left heart syndrome and 12 with univentricular heart to 42 children without heart defect. METHODS: Motor development was assessed with the Alberta Infant Motor Scale and Movement Assessment Battery for Children (Movement ABC). RESULTS: Children with hypoplastic left heart syndrome or univentricular heart had significantly lower scores on the Alberta Infant Motor Scale test at the age of 1 and on the Movement ABC test at the age of 5 years compared with controls. Children with clear abnormalities on brain magnetic resonance imaging had lower scores compared with those with normal images or mild changes, and their relative motor scores decreased during follow-up. CONCLUSIONS: Some children with univentricular heart defects may benefit from physiotherapeutic interventions to support their motor development. PMID- 27661240 TI - Commentary on "Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects". PMID- 27661241 TI - Sporting Activities and Quality of Life in Children With Hemophilia: An Observational Study. AB - INTRODUCTION: Sports activities are part of multidisciplinary treatments in people with hemophilia. AIM: The objective of this study was to assess the incidence of sports activities in the quality of life as perceived by children with hemophilia. METHODS: A total of 53 children with hemophilia aged 7 to 13 years and 51 children without hemophilia were evaluated. The perception of quality of life, clinical variables, and the frequency of sports activities were registered. The joint condition of patients with hemophilia was measured with the Spanish version of the Haemophilia Joint Health Score. RESULTS: There were no significant differences in the perception of quality of life between children with hemophilia and children without hemophilia. Sports activities in people with hemophilia promoted a greater health satisfaction. CONCLUSIONS: Sports activity in children with hemophilia is associated with an improved quality of life and joint health. It is also associated with improved psychosocial wellness. PMID- 27661242 TI - Commentary on "Sporting Activities and Quality of Life in Children With Hemophilia: An Observational Study". PMID- 27661243 TI - Virtual Sensorimotor Training for Balance: Pilot Study Results for Children With Fetal Alcohol Spectrum Disorders. AB - PURPOSE: To examine the effects of Sensorimotor Training to Affect Balance, Engagement, and Learning (STABEL), a virtual reality system to train sensory adaptation for balance control, for children with fetal alcohol spectrum disorders (FASDs). METHODS: Twenty-three children with FASDs received STABEL training in a university laboratory, or home, or were controls. The Movement Assessment Battery for Children-2nd edition (MABC-2) and Pediatric Clinical Test of Sensory Interaction for Balance-2 (P-CTSIB-2) were analyzed by group (lab, home, and control), session (pre-STABEL, 1 week post-STABEL, and 1 month post STABEL), and group-by-session interaction. RESULTS: Significant effects were group and session for MABC-2 Balance and interaction for MABC-2 Total Motor and P CTSIB-2. CONCLUSION: Preliminary results support improved sensory adaptation, balance, and motor performance post-STABEL, which warrant further study with a larger, randomized sample. PMID- 27661244 TI - Commentary on "Virtual Sensorimotor Training for Balance: Pilot Study Results for Children With Fetal Alcohol Spectrum Disorders". PMID- 27661245 TI - Does Exercise Decrease Pain via Conditioned Pain Modulation in Adolescents? AB - PURPOSE: Pain relief after exercise, exercise-induced hypoalgesia (EIH), is established across the lifespan. Conditioned pain modulation (CPM: pain inhibits pain) may be a mechanism for EIH. METHODS: In 55 adolescents, pressure pain thresholds were measured before and after exercise (deltoid, quadriceps, and nail bed) and during CPM at the nail bed and deltoid test stimulus sites. The relationship between EIH and CPM was explored. RESULTS: EIH occurred at deltoid and quadriceps; CPM occurred at nail bed and deltoid. CPM and EIH correlated at deltoid; adolescents with greater CPM experienced greater pain relief after exercise. At this site, CPM predicted 5.4% of EIH. Arm lean mass did not add a significant effect. Peak exercise pain did not influence EIH. Adolescents with none, minimal, moderate, or severe peak exercise pain experienced similar EIH. CONCLUSIONS: A potential relationship exists between CPM and EIH in adolescents. Pediatric physical therapists should consider the CPM response when prescribing exercise as a pain management tool. PMID- 27661246 TI - Commentary on "Does Exercise Decrease Pain via Conditioned Pain Modulation in Adolescents?". PMID- 27661247 TI - Effect of Playground Environments on the Physical Activity of Children With Ambulatory Cerebral Palsy. AB - PURPOSE: To compare the effect of 2 different playground environments on the physical activity of children with ambulatory cerebral palsy during their playground play. METHODS: Five 7- to 8-year-old children with cerebral palsy (Gross Motor Functional Classification System [GMFCS] level II) participated. Using an alternating treatment, single-subject design, stride patterns were obtained using an activity monitor on an Americans with Disabilities Act (ADA) compliant and noncompliant playground. Visual and statistical analysis of the stride data was used to analyze the effect of the playground environments. RESULTS: Four of the 5 participants increased the number of strides on an ADA compliant playground. CONCLUSION: Children with cerebral palsy (GMFCS II) may benefit from an ADA-compliant playground to increase their physical activity. PMID- 27661248 TI - Commentary on "Effect of Playground Environments on the Physical Activity of Children With Ambulatory Cerebral Palsy". PMID- 27661249 TI - Technology for Children With Brain Injury and Motor Disability: Executive Summary From Research Summit IV. AB - Advances in technology show promise as tools to optimize functional mobility, independence, and participation in infants and children with motor disability due to brain injury. Although technologies are often used in adult rehabilitation, these have not been widely applied to rehabilitation of infants and children. In October 2015, the Academy of Pediatric Physical Therapy sponsored Research Summit IV, "Innovations in Technology for Children With Brain Insults: Maximizing Outcomes." The summit included pediatric physical therapist researchers, experts from other scientific fields, funding agencies, and consumers. Participants identified challenges in implementing technology in pediatric rehabilitation including accessibility, affordability, managing large data sets, and identifying relevant data elements. Participants identified 4 key areas for technology development: to determine (1) thresholds for learning, (2) appropriate transfer to independence, (3) optimal measurement of subtle changes, and (4) how to adapt to growth and changing abilities. PMID- 27661251 TI - Letter to the Editor. PMID- 27661250 TI - The Effects of Orthopedic Manual Physical Therapy in the Management of Juvenile Idiopathic Arthritis: A Case Report. AB - PURPOSE: Juvenile idiopathic arthritis (JIA) is a cause of disability in childhood. Little research exists concerning physical therapy management, and no evidence exists for orthopedic manual physical therapy (OMPT) for JIA. The purpose of this case report is to describe the use of OMPT in combination with therapeutic exercise in the successful treatment of a child with oligoarticular JIA. KEY POINTS: A 6-year-old girl with oligoarticular JIA presented with elbow pain and stiffness interfering with function. Treatment consisted of OMPT in combination with therapeutic exercise and a home exercise program. CONCLUSIONS: Improvements were demonstrated in elbow range of motion, pain, Childhood Health Assessment Questionnaire, Pediatric Outcomes Data Collection Instrument, and the Patient Specific Functional Scale. RECOMMENDATIONS FOR CLINICAL PRACTICE: Orthopedic manual physical therapy may be considered as a treatment of a child with JIA. RECOMMENDATIONS: We provide evidence that OMPT may be considered as a treatment of a child with JIA. PMID- 27661252 TI - Synthesis of Enantioenriched 2-Alkyl Piperidine Derivatives through Asymmetric Reduction of Pyridinium Salts. AB - An Ir-catalyzed enantioselective hydrogenation of 2-alkyl-pyridines has been developed using ligand MeO-BoQPhos. High levels of enantioselectivities up to 93:7 er were obtained. The resulting enantioenriched piperidines can be readily converted into biologically interesting molecules such as the fused tricyclic structures 5, 6, and 7 in 99:1 er, providing a novel, concise synthetic route to this family of chiral piperidine-containing compounds. PMID- 27661253 TI - DAPK interacts with Patronin and the microtubule cytoskeleton in epidermal development and wound repair. AB - Epidermal barrier epithelia form a first line of defense against the environment, protecting animals against infection and repairing physical damage. In C. elegans, death-associated protein kinase (DAPK-1) regulates epidermal morphogenesis, innate immunity and wound repair. Combining genetic suppressor screens and pharmacological tests, we find that DAPK-1 maintains epidermal tissue integrity through regulation of the microtubule (MT) cytoskeleton. dapk-1 epidermal phenotypes are suppressed by treatment with microtubule-destabilizing drugs and mimicked or enhanced by microtubule-stabilizing drugs. Loss of function in ptrn-1, the C. elegans member of the Patronin/Nezha/CAMSAP family of MT minus end binding proteins, suppresses dapk-1 epidermal and innate immunity phenotypes. Over-expression of the MT-binding CKK domain of PTRN-1 triggers epidermal and immunity defects resembling those of dapk-1 mutants, and PTRN-1 localization is regulated by DAPK-1. DAPK-1 and PTRN-1 physically interact in co immunoprecipitation experiments, and DAPK-1 itself undergoes MT-dependent transport. Our results uncover an unexpected interdependence of DAPK-1 and the microtubule cytoskeleton in maintenance of epidermal integrity. PMID- 27661256 TI - Film Thickness Determines Cell Growth and Cell Sheet Detachment from Spin-Coated Poly(N-Isopropylacrylamide) Substrates. AB - Poly(N-isopropylacrylamide) (pNIPAm) is widely used to fabricate thermoresponsive surfaces for cell sheet detachment. Many complex and expensive techniques have been employed to produce pNIPAm substrates for cell culture. The spin-coating technique allows rapid fabrication of pNIPAm substrates with high reproducibility and uniformity. In this study, the dynamics of cell attachment, proliferation, and function on non-cross-linked spin-coated pNIPAm films of different thicknesses were investigated. The measurements of advancing contact angle revealed increasing contact angles with increasing film thickness. Results suggest that more hydrophilic 50 and 80 nm thin pNIPAm films are more preferable for cell sheet fabrication, whereas more hydrophobic 300 and 900 nm thick spin coated pNIPAm films impede cell attachment. These changes in cell behavior were correlated with changes in thickness and hydration of pNIPAm films. The control of pNIPAm film thickness using the spin-coating technique offers an effective tool for cell sheet-based tissue engineering. PMID- 27661257 TI - Reversible Insulin Hexamer Assembly Promoted by Ethyl Violet: pH-Controlled Uptake and Release. AB - Therapeutically improved long-acting insulin preparations require in-depth understanding of the hexamer assembly, structural selectivity, and its stability in solution. This Letter demonstrates, for the first time, an efficient method for the hexamerization of human insulin by a structure-specific triphenylmethane (TPM) dye, Ethyl Violet (EV), particularly, in the absence of Zn2+. Upon detailed spectroscopic evaluation and comparison with other TPM homologues, we establish that the diethylamino phenyl arms of EV are specific and effective in clipping the three dimer helices in a hexameric assembly. We establish that at physiological pH 7.4 and in the presence of the EV, insulin exists predominantly in its hexameric form, a condition appropriate for storage and preparation of long-acting insulin formulations. On the other hand, the disassembly of the hexamer into the monomeric form is accomplished at pH 5, highlighting its potential as a delivery vehicle for such custom-modified dyes/drugs. PMID- 27661254 TI - Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling. AB - Epithelial cells and their underlying basement membranes (BMs) slide along each other to renew epithelia, shape organs, and enlarge BM openings. How BM sliding is controlled, however, is poorly understood. Using genetic and live cell imaging approaches during uterine-vulval attachment in C. elegans, we have discovered that the invasive uterine anchor cell activates Notch signaling in neighboring uterine cells at the boundary of the BM gap through which it invades to promote BM sliding. Through an RNAi screen, we found that Notch activation upregulates expression of ctg-1, which encodes a Sec14-GOLD protein, a member of the Sec14 phosphatidylinositol-transfer protein superfamily that is implicated in vesicle trafficking. Through photobleaching, targeted knockdown, and cell-specific rescue, our results suggest that CTG-1 restricts BM adhesion receptor DGN-1 (dystroglycan) trafficking to the cell-BM interface, which promotes BM sliding. Together, these studies reveal a new morphogenetic signaling pathway that controls BM sliding to remodel tissues. PMID- 27661258 TI - Quantum Dynamics Simulations of Excited State Energy Transfer in a Zinc-Free-Base Porphyrin Dyad. AB - Rational design of artificial light-harvesting molecular architectures entails building systems that absorb strongly in the visible and near-IR region of the electromagnetic spectrum and also funnel excited state energy to a single site. The ability to model nonadiabatic processes, such as excited-state energy transfer (EET), that occur on a picosecond time scale can aid in the development of novel artificial light-harvesting arrays. A combination of density functional theory (DFT), time-dependent DFT, tight-binding molecular dynamics, and quantum dynamics is employed here to simulate EET in the ZnFbPhi dyad, a model artificial light-harvesting array that undergoes EET with an experimentally measured rate constant of (3.5 ps)-1 upon excitation at 550 nm in toluene [ Yang et al. J. Phys. Chem. B 1998 , 102 , 9426 - 9436 ]. We find that to successfully simulate the EET process, it is important to (1) include coupling between nuclear and electronic degrees of freedom in the QD simulation, (2) account for Coulomb coupling between the electron and hole wavepackets, and (3) parametrize the extended Huckel model Hamiltonian employed in the QD simulations with respect to the DFT. PMID- 27661255 TI - Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. AB - We recently found that nucleosomes directly block access of CRISPR/Cas9 to DNA (Horlbeck et al., 2016). Here, we build on this observation with a comprehensive algorithm that incorporates chromatin, position, and sequence features to accurately predict highly effective single guide RNAs (sgRNAs) for targeting nuclease-dead Cas9-mediated transcriptional repression (CRISPRi) and activation (CRISPRa). We use this algorithm to design next-generation genome-scale CRISPRi and CRISPRa libraries targeting human and mouse genomes. A CRISPRi screen for essential genes in K562 cells demonstrates that the large majority of sgRNAs are highly active. We also find CRISPRi does not exhibit any detectable non-specific toxicity recently observed with CRISPR nuclease approaches. Precision-recall analysis shows that we detect over 90% of essential genes with minimal false positives using a compact 5 sgRNA/gene library. Our results establish CRISPRi and CRISPRa as premier tools for loss- or gain-of-function studies and provide a general strategy for identifying Cas9 target sites. PMID- 27661259 TI - Regioselective and Stereoselective Pd-Catalyzed Intramolecular Arylation of Furans: Access to Spirooxindoles and 5H-Furo[2,3-c]quinolin-4-ones. AB - Herein, we report regio- and stereoselective intramolecular direct arylations of N-(2-bromophenyl)-2-furancarboxamides 1 to produce spirooxindoles 2 and 5H furo[2,3-c]quinolin-4-ones 3 under different reaction conditions. Specifically, in the presence of Pd(PPh3)4 as a catalyst, PPh3 as a ligand, and K2CO3 as a base, substrates 1 underwent intramolecular alpha-arylation, possibly via a Heck insertion pathway, to provide 2, with the Z-isomer being favored. When the base was t-BuOLi and R1 was an aryl group, the reaction favored E-2, possibly via an electrophilic palladation pathway. In contrast, in the presence of PdCl2 as a catalyst, (o-OMePh)3P as a ligand, and PivOH as an additive, substrates 1 underwent intramolecular beta-arylation to provide 3, possibly via a concerted metalation-deprotonation process. PMID- 27661260 TI - Low-Power, Self-Rectifying, and Forming-Free Memristor with an Asymmetric Programing Voltage for a High-Density Crossbar Application. AB - A Pt/NbOx/TiOy/NbOx/TiN stack integrated on a 30 nm contact via shows a programming current as low as 10 nA and 1 pA for the set and reset switching, respectively, and a self-rectifying ratio as high as ~105, which are suitable characteristics for low-power memristor applications. It also shows a forming free characteristic. A charge-trap-associated switching model is proposed to account for this self-rectifying memrisive behavior. In addition, an asymmetric voltage scheme (AVS) to decrease the write power consumption by utilizing this self-rectifying memristor is also described. When the device is used in a 1000 * 1000 crossbar array with the AVS, the programming power can be decreased to 8.0% of the power consumption of a conventional biasing scheme. If the AVS is combined with a nonlinear selector, a power consumption reduction to 0.31% of the reference value is possible. PMID- 27661261 TI - Improved Electrochemical Performance of LiFePO4@N-Doped Carbon Nanocomposites Using Polybenzoxazine as Nitrogen and Carbon Sources. AB - Polybenzoxazine is used as a novel carbon and nitrogen source for coating LiFePO4 to obtain LiFePO4@nitrogen-doped carbon (LFP@NC) nanocomposites. The nitrogen doped graphene-like carbon that is in situ coated on nanometer-sized LiFePO4 particles can effectively enhance the electrical conductivity and provide fast Li+ transport paths. When used as a cathode material for lithium-ion batteries, the LFP@NC nanocomposite (88.4 wt % of LiFePO4) exhibits a favorable rate performance and stable cycling performance. PMID- 27661262 TI - Differing Procedures for Recording Mortality Statistics in Scandinavia. AB - BACKGROUND: There may be various reasons for differences in suicide rates between countries and over time within a country. One reason can be different registration practices. AIMS: The purpose of this study was to describe and compare the present procedures for mortality and suicide registration in the three Scandinavian countries and to illustrate potential sources of error in the registration of suicide. METHOD: Information about registration practices and classification procedures was obtained from the cause of death registers in Norway, Sweden, and Denmark. In addition, we received information from experts in the field in each country. RESULTS: Sweden uses event of undetermined intent more frequently than Denmark does, and Denmark more frequently than Norway. There seems to be somewhat more uncertainty among deaths classified as ill-defined and unknown cause of mortality in Norway, compared with the other two countries. Sweden performs more forensic autopsies than Norway, and Norway more than Denmark. In Denmark, in cases of a suspected unnatural manner of death, a thorough external examination of the deceased is performed. CONCLUSION: Differences in the classification of causes of death and in postmortem examinations exist in Scandinavian countries. These differences might influence the suicide statistics in Scandinavia. PMID- 27661265 TI - Effect of Exergaming on Physiological Response and Enjoyment During Recess in Elementary School-Aged Children: A Pilot Study. AB - OBJECTIVE: With an increasing rate of childhood obesity, it is critical to find fun and effective ways of providing children with opportunities to be physically active while at school to mediate this outcome. Using games as a mode of exercise (Exergaming) could be one such way. We aimed to compare the physiologic response and enjoyment of elementary school children when playing Xbox(r) Kinect(r) versus participating in regular activities during recess. MATERIALS AND METHODS: Twenty four children participated individually once in Kinect and once in regular activity sessions on separate days during recess for the allotted time. Sessions were at least 1 week apart, and the order of the sessions was randomized. During the Kinect session, participants played the Reflex Ridge game. During the regular session, participants engaged in self-selected activities. Energy expenditure, metabolic equivalents of task (METS), time in moderate to vigorous activity, percentage of activity in sedentary, light, moderate, vigorous and very vigorous levels, heart rate, rate of perceived exertion (RPE), and Physical Activity Enjoyment Scale were measured for each session and compared using a paired samples t-test. RESULTS: Significantly greater RPE (P = 0.024), percentage of activity at sedentary (P = 0.019), very vigorous (P < 0.001) levels, and lesser percentage of activity at moderate level (P = 0.008) were noted during the Kinect session. CONCLUSION: Playing Kinect was comparable to playing outside with classmates. When necessary, such as in inclement weather, whole-body interactive videogames can be a viable alternative physical activity. However, this has to be validated with a larger sample study. PMID- 27661264 TI - Protein-based therapeutic for anemia caused by dyserythropoiesis. AB - INTRODUCTION: Major advances have been recently made in understanding the molecular determinants of dyserythropoiesis, particularly due to recent works in beta-thalassemia. The purpose of this review is devoted to underline the role of some proteins recently evidenced in the field, that may be new alternative therapeutic targets in the near future to alleviate different types of anemia. Areas covered: This review covers the contemporary aspects of some proteins involved in various types of dyserythropoiesis, including the transcriptional factor GATA-1 and its protective chaperone HSP70, but also cytokines of the transforming growth factor beta (TFG-beta) family, TGF-beta1 and GDF-11, and hormones as erythroferrone. It will be not exhaustive, but based on major recent published works from the literature in the past three years. Expert commentary: Sotatercept and lustatercept, two activin receptor II ligand traps that block GDF 11, are candidate drugs providing therapeutic hope in different types of ineffective erythropoiesis, including myelodysplastic syndromes (MDS) and beta thalassemia. Furthermore, a new concept emerges to consider erythroid lineage in the bone marrow as an endocrine gland. PMID- 27661263 TI - The moderating effect of religiosity on caregiving burden and depressive symptoms in caregivers of patients with dementia. AB - OBJECTIVES: This study explored whether religiosity/spirituality has a protective role against negative caregiving outcomes, in a large multicenter nationwide sample of caregivers of patients with dementia in South Korea. Additionally, this study was the first to examine whether religiosity/spirituality could affect caregiving outcomes according to the various religious affiliations of caregivers. METHODS: The study was conducted on a sample of 476 caregivers of patients with dementia participated in the Clinical Research Center for Dementia of South Korea (CREDOS). We examined the moderating effect of each of the three dimensions of religiosity/spirituality (organizational religious activity, ORA; non-organizational religious activity, NORA; intrinsic religiosity, IR) on the relationship between activities of daily living (ADL) of patients with dementia and caregiving burden and depressive symptoms of caregivers, using a series of hierarchical regression analyses. In addition, these analyses were conducted according to the religious affiliations of the caregivers. RESULTS: ORA, NORA, and IR of religiosity/spirituality alleviated the effect of ADL of patients on caregiving burden. ORA and IR moderated the relationship between ADL of patients and depressive symptoms of caregivers. These moderating effects of religiosity on caregiving outcomes were different according to various religious groups. CONCLUSION: We have identified religiosity/spirituality as a protective factor for caregivers of patients with dementia. The sub-dimensions of religiosity as moderators were different by religious affiliations of caregivers. Further studies are needed to investigate the specific religiosity-related factors which could positively impact the mental health of the caregivers of patients with dementia by religions. PMID- 27661267 TI - SUCCESSFUL REPAIR OF IATROGENIC URETERAL INJURY IN A PATIENT WITH ECTOPIC CROSSED AND FUSED RIGHT KIDNEY BY URETEROURETEROSTOMY. AB - Congenital renal malformations are the most common congenital malformations in humans, the most common being horseshoe kidney with joined lower poles present in up to 0.25% of general population. To the contrary renal fusions with ectopia are amongst the rare malformations affecting 1 in 2000 examined cadavers. Males are affected slightly more often then females (3:2), left to right crosses being more frequent. The value of early diagnosis of asymptomatic renal malformation is uncertain, except when other abnormalities might point to them and they can affect the clinical management strategy (severe ear deformity with facial malformation, gynecological abnormalities). In females concomitant abnormalities of kidneys and paramesonephric duct derivatives are common, with up to 40% of women with uterine malformations reported to have various congenital renal abnormalities. Even though there are occasional examples of surgical repair of the injured kidneys with crossed-fused malformation the majority of surgical cases resort to renal resection. We presented a rare case of complex genitourinary malformation with crossed fused disk kidney diagnosed after the iatrogenic injury to the right ureter after emergent gynecological surgery. Rare pathology and presentation was diagnosed by IVP and confirmed during operation. We have constructed an ipsilateral ureteroureterostomy to drain the right portion of fused kidney. Urinary flow was satisfactory with no significant nephrostomy tube drainage next day, allowing the nephrostomy tube removal. Postsurgical evaluation by IVP has demonstrated a good flow from both kidney and no detectable anastomotic leaks. Postsurgical recovery was uneventful. After 2 years from operation IVP data did not changed. It must be noted, that Ectopic kidneys are frequently malformed and have an abnormal ureteral drainage leading to incontinence and frequent UTIs. PMID- 27661268 TI - CELLULAR FIBROUS DERMATOFIBROMA OF THE SOLE. AB - Cellular fibrous dermatofibroma is a rare variant of dermatofibroma/histiocytoma. We present a 61 years old female with a slow-growing, firm tumor on the sole of her right foot. The tumor was removed by slow Mohs surgery within 2 cm negative margin. Histopathologic investigation revealed a nodular encapsulated tumor composed of spindle and some epithelioid cells in a storiform growth pattern. Minimal mitotic activity was reported, however without evidence of atypical mitoses. Tumor cells expressed CD10, focally smooth muscle antigen and desmin, but remained negative for S100 protein and CD34. The diagnosis of cellular fibrous dermatofibroma was confirmed. The defect was closed by full thickness skin graft. PMID- 27661266 TI - Detection of a phosphorylated glycine-serine linker in an IgG-based fusion protein. AB - Molecular mass determination by electrospray ionization mass spectrometry of a recombinant IgG-based fusion protein (mAb1-F) produced in human embryonic kidney (HEK) cells demonstrated the presence of a dominant +79 Da product variant. Using LC-MS tryptic peptide mapping analysis and collision-induced dissociation (CID) and electron-transfer/higher-energy collision dissociation fragmentations, the modification was localized to the C-terminal serine residue of a glycine-serine linker [(G4S)2] of a fused heavy chain containing in total 2 (G4S)2-linkers. The modification was identified as a phosphorylation (+79.97 Da) by the presence of a 98 Da neutral loss reaction with CID, by spiking a synthetic phosphoserine peptide, and by dephosphorylation with alkaline phosphatase. A thermolysin digest combined with higher-energy collision dissociation (HCD) positioned the phosphoserine to one specific glycine-serine linker of the fused heavy chain, and the relative level of phosphorylated linker was determined to be 11.3% and 0.4% by LC-MS when the fusion protein was transiently expressed in HEK or in stably transformed Chinese hamster ovary cells, respectively. This observation demonstrates that fusions with glycine-serine linker sequences should be carefully evaluated during drug development to prevent the introduction of a phosphorylation site in therapeutic fusion proteins. PMID- 27661269 TI - [THE RAPID TEST METHOD OF IDENTIFICATION OF THE TYPE OF GROWTH OF THE JAW BONE ON THE ORTHOPANTOMOGRAM]. AB - The roentgenological methods of research take the lead in the diacrisis of dentofacial anomalies, they are of the utmost importance as for the identification of the jaws' growth character, so too for the generation of the treatment planning and of the expected response to the treatment. The type of the jaw growth is identified by the means of a basal angle on the teleroentgenography (TRG). The objective of the research was to develop a rapid test method of identification of the type of growth by means of a basal angle on the orthopantomogram (OPTG). The comparison of 0,05) during the comparison of angles' indexes on the TRG and OPTG. The proposed rapid test method allows to identify the type of growth of the mandibular bones by the means of basal angle 40 g/day (OR=3.53 [95% SIota 1.36-9.17], r=0.009), Gln11Gln genotype of the TLR7 gene (OR=4.56 [95% SIota 1.57-13.22], r=0.005), presence of chronic cholecystitis and/or pancreatitis (OR=5.30 [95% SIota 1.84-15.25], r=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and AST>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity - 85.5%, specificity - 68.3%, total number of the appropriate assignments - 76.8%, positive and negative predictive value - 72,6% and 82.7%,, respectively, the AUC ROC-curve - 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual approaches to prescribing antiviral therapy for CHC. PMID- 27661276 TI - THE USEFULNESS OF MONITORING THE NEUTROPHIL TO LYMPHOCYTE RATIO IN PATIENTS WITH PERIPHERAL VERTIGO. AB - The purpose of this study was to evaluate the usefulness of the neutrophil to lymphocyte ratio (NLR) in a differential diagnosis and follow-up of patients with peripheral vertigo. Twenty patients with benign positional paroxysmal vertigo (BPPV) and 20 patients diagnosed with vestibular neuritis (VN) were included in the study. Serum samples were analysed at the initial presentation and on the seventh day of admission retrospectively. The WBC (white blood cell) count was 10500+/-2100 /mm3, the neutrophil count was 4700+/-1100/mm3, the lymphocyte count was 5000+/-1200/mm3 and the NLR was 0.9+/-0.2 in the VN group. In patients with BPPV, the WBC count was 9200+/-1300/mm3, the neutrophil count was 5200+/ 1200/mm3, the lymphocyte count was 3100+/-1200/mm3 and the NLR was 1.9+/-0.9. The NLR was lower in patients with VN than in patients diagnosed with BPPV. The WBC and lymphocyte count was significantly higher in the patients with VN than in the patients diagnosed with BPPV. Within the first week of admission, the WBC and lymphocyte counts in patients with VN decreased, and the NLR was more elevated than at the admission. It is highly recommended that NLR is used in the diagnosis and follow-up of the most commonly observed aetiological factors of peripheral vertigo, BPPV and VN. PMID- 27661277 TI - [CONGENITAL DEFICIENCY OF COAGULATION FACTOR V]. AB - The study was designed to investigate the 5 year old girl with rare bleeding disorder -deficiency of coagulation factor V. The diagnosis was based on detail family history, physical examination and para-clinical data analyses. The age of patient, purpura, this has been detected from early age, positive family history, non-controlled, longtime bleeding, inadequate trauma of the tongue, which did not resolve after surgery, strong hypocoagulation, which was slightly improved, after several plasma transfusions. This allowed us to suggest the existence of the congenital coagulopathy, which was confirmed by the investigation of coagulation factors - particularly the deficiency of factor V was detected. PMID- 27661278 TI - IMMUNE CHANGES IN NEWBORN INFANTS WITH GASTROINTESTINAL FAILURE REQUIRING INTENSIVE CARE. AB - Newborns in critical conditions, because of the natureof the immune system, have the greatest risk of realization of immune deficiency, especially with gastrointestinal failure. We analyzed 44 cases of diseases in newborns in critical conditions and 20 cases without and studied the clinical and laboratory signs of immunological disorders, organpathology, gene expressionToll likereceptor type 2. In newborns requiring intensive care, the frequency of gastrointestinal failure registration in 40,9%. Gastrointestinal failure leads to increased amounts of other affected systems, severity of systemic inflammation, gene expressionToll-likereceptor type 2, a marker of apoptosis of lymphocytes CD95+, inhibition lymphocyte germ of immune system due to fraction of CD4+,the severity of the clinical condition. In newbornsin intensive care gastrointestinal failure is recorded at a frequency of 40,9%, is a component of multiple organ dysfunction syndrome, increases the expression of the geneToll-likereceptor type 2, implements violation adequate response humoral immunity, activates apoptosis of lymphocytes, which increases the severity of the patients. PMID- 27661279 TI - [PHYSICAL DEVELOPMENT OF CHILDREN IN ORPHANAGES]. AB - Aim - to define the parameters of physical development of children in orphanages. 72 children (45 boys, 27 girls) without chronic debilitating diseases and condition aged from 1 to 6 years from Tbilisi and Makhinjauri orphanages (Georgia) were assessed. Height and weight of all subjects were measured and BMI, height SDS (standard deviation score) and weight SDS were calculated. Data were compared to the normal values (national data). The retardation of the physical development were seen along almost all findings. The significant differences regarding age and gender were not revealed. The most expressed tendency to delay was expressed in the height of boys, particularly aged 3-5 years. Our data confirm that institution upbringing has a negative impact on the growth of children of 1-6 years of age. In children aged from 1 to 6 years who are healthy but live in orphanages there is a marked tendency to lag behind in physical development, mainly in height. The above-mentioned confirms the opinion about negative impact of upbringing in orphanages on the physical development of children. PMID- 27661280 TI - [IRON-DEFICIENCY ANEMIA AS A FACTOR OF DEVELOPMENT OF ASTHENIA SYNDROME]. AB - The aim of this research was to determine the frequency and degree of severity of asthenic syndrome (AS) and estimation of physical health of women with iron deficiency anemia (IDA) and without it. 30 women were inspected with the set diagnosis of IDA and 20 nearly were healthy. All participants were assessed according objective status. AS was determined by the scale of estimation of asthenia - Scale Asthenic Conditions (SAC) of LD Malkova, the scale of subjective evaluation of asthenia (MFI-20). Level of somatic health was appraised by methodology of LG Apanasenko. As a result of research it was found that in 100% of women with IDA , which more often occurs with expressed hypoxic syndrome, that aggravates a process of AS. The severity of AS directly depends on the degree of IDA. The presence of IDA contributes to decreased physical activity of patients because of progressive weakness and fatigue. The level of physical health is rated as "low" due to low reserve capacity of the cardiorespiratory system and power qualities. In the control group, incidence of AS is significantly lower (40 55%) and the degree of severity in most cases is weak and moderate. The obtained data allow to make the conclusion that the medicines for correction of AS must be necessarily included in therapy of IDA. PMID- 27661281 TI - [STUDY OF LIPIDS SEED'S OIL OF VITEX AGNUS CASTUS GROWING IN GEORGIA]. AB - There was established the lipid composition of the seeds of Vitex agnus castus L. by the qualitative and quantitative methods of analyses. There were received neutral lipids from the seeds by extraction with hexane in the yield 10%, counted on dry material. For the divide of neutral lipids there was used silica gel plates LS 5/40 in the systems of solvents: 1. petroleum ether-diethylether-acidum aceticum (85:14:1), 2. hexane-diethylether (1:1). After obtaining neutral lipids from the residual plant shrot pollar lipids was extracted with the mixture of chloroform-methanol (2:1) and was divided on silica gel plates LS 5/40, mobile phase: 1. chloroform-methanol-25% ammonium hydrate 2. chloroform-methanol icy acetic acid-water (170:25:25:6). In the sum of polar lipids qualitatively were established phospholipids: lisophosphatidylcholine, phosphatidylinosit, phospatidylethanolamine and N-acylphosphatidylethanolamine, in neutral lipids, hydrocarbons, triglycerids, free fatty acids and sterines. By the method of high performance liquid chromatography analyses there were identified following free fatty acids: lauric, myristic, palmitic, stearic, linolic, linolenic, arachidic and begenic, unsaturated oleic and polyunsaturated linolic and linolenic acids. obtained oil with unique composition from the seeds of Vitex agnus-castus indicates to its high biological activity and importance for usage in medicine. PMID- 27661282 TI - [SCREENING OF WILD SPREAD AND CULTIVATED OF BUXUS SPECIES GROWING IN GEORGIA ON THE CONTENT OF ALKALOIDS AND BIOLOGICAL ACTIVITY]. AB - Georgian flora is represented by about 4150 plant species. Many important alkaloid-containing plant species and among of them are species Buxus L. of genus in Adjara. The aims of the research were: sequential screening of the plants for the consistence of alkaloids; Study of anatomical characteristics of Buxus colchica Pojark. and revealing of specific pharmacological activity of steroidal alkaloids. The objects of research were B. colchica, B. balearika and B. sempervirens, growing in Adjara (Georgia), collected in active phase of flowering of the plants. There were revealed 370 species of alkaloid containing plants. Sum of alkaloids and crude aqueous extract have spasmolitic and antihistaminic activity. Experimental anatomical research of diagnostic characteristics of the bines showed the existence of monocyclic transient system with fiber like tracheids, dorsoventral mesophyll of the leaves; the structure for the upper part of epidermis is linear and the lower part is curved, type of stomata is paracitic. PMID- 27661283 TI - INTERSYSTEM INTEGRATION IN TERMS OF THE EDUCATIONAL PROCESS IN THE INITIAL COURSES OF HIGHER MEDICAL SCHOOL. AB - The study was conducted as part of research work "Features of integrative and autonomic functions in the process of adaptation to the intellectual, emotional and physical stress" of the Department of Physiology of KhNMU. The aim of this work was to study the intersystem relationships that are the basis for the development of the body's resistance to the effects of stress factors, i.e., the development of adaptation syndrome in medical students. The object of the study were 217 students of 1-3 courses, which were examined in terms of the educational process. The features of intersystem integration the cardiorespiratory system on the basis of conjugation and integration of brain activity indeces based on intellectual efficiency in terms of a correction test. The study of the psychophysiological indicators complex in dynamics (3 years) revealed the formation of chronic emotional stress in medical students, the severity of which depends on the individual psychophysiological status of students. It was set that the formation of the adaptive optimum with psychoemotional stress occurs in only in 40% of students. Most of the students (60 %) indicate or initially insufficient adaptive capabilities, or an excessive rate, which naturally lead to psychological and autonomic disturbances in the organism. PMID- 27661284 TI - [PREDICTING OF RISK OF SOIL CONTAMINATION BY DIFFERENT CLASSES OF FUNGICIDES IN SOIL AND CLIMATIC CONDITIONS OF UKRAINE]. AB - Application of pesticides in modern agriculture is a powerful permanent risk factor for public health and the natural environment. The aim of the study was a comparative hygienic assessment of soil pollution hazards by the most widely used herbicides of different chemical classes (sulfonylureas, imidazolinones, pyrimidinyl (thio) benzoates, semicarbazones). Hygienic field experiment for studying of the dynamics of residual amounts of the test substances in the soil under different climatic zones of Ukraine was conducted. Half life periods (DT50) or herbicides in soil were calculated using the method of mathematical modeling. Ecotoxicological risk of herbicides on ecosystems and ecological communities was determined. It was established that bispyribac-sodium (pyrimidinyl (thio) benzoates) and imidazolinones are persist the longest time in soil and most rapidly degradable is diflufenzopyr (semicarbazone); ecotoxicological risk of the studied herbicides for terrestrial biocenoses of Ukraine by 4-6 orders of magnitude lower than dihlordifeniltrihlormetilmetan (DDT). PMID- 27661285 TI - [INFLUENCE OF THE INTRA-ABDOMINAL HYPERTENSION ON THE BLOOD COAGULATION SYSTEM (EXPERIMENTAL STUDY)]. AB - The analysis of the influence of the intra-abdominal hypertension on the blood coagulation system by carrying out an experimental research with laboratory animals is presented in article. After simulating intra-abdominal hypertension with different degree and exposition we made the laboratory research of blood coagulation system (fibrinogen, PTI, SFMC, APTT) and ELISA research on the concentration of the modern marker of thrombozis - D-dimer. The results in article clearly demonstrate that there is a direct linear dependence of level of fibrinogen and SFMC on degree of intra-abdominal hypertension, and the multidirectional changes of indicators with increase of intra-abdominal hypertension duration - towards hypercoagulation for 3-12 hours, and then by 24 o'clock - in the opposite direction towards hypocoagulation. Perhaps, it is explained with development of organ dysfunction and a coagulopathy of consumption. Indicator D-dimer has also direct linear dependence on the intra abdominal hypertension level with contents peak at 3 hour exposition, and at all intra-abdominal hypertension levels, more than 2-fold rise of D-dimer level is statistically significant. PMID- 27661286 TI - [INFLUENCE OF EMOTIONAL STRESS ON CELLULAR IMMUNITY EXPOSED TO LOW DOSE OF GAMMA RADIATION IN THE REMOTE PERIOD (EXPERIMENTAL STUDY)]. AB - The study aim was to investigate the combined influence of emotional stress and low doses of ionizing radiation (0.2 Gr) on cellular immunity of laboratory animals in the remote period. One hundred and twenty Wistar rats were divided into 4 groups: 1 group control, 2 group - exposed to gamma-radiation, 3 group - exposed to emotional stress, 4 group was exposed to the combined influence of emotional stress and gamma-radiation. Emotional stress was simulated by tail suspension. Animals from groups 2 and 4 were exposed to a single dose of 0.2 Gr 90 days prior the investigation via "TERAGAM" 60Co (ISOTREND spol. s.r.o., Check Republic). The results of our study show that in a remote period after exposure to a low dose of gamma-radiation the decrease of quantitative and increase of qualitative indicators of cellular immunity are observed, which is manifested by lymphopenia and decease of CD3+- CD4+ - and CD8+-lymphocytes subpopulations, and lymphokin-producing capacity of leucocytes. The late phase of stress-reaction is characterized by lymphocytosis, increase in absolute numbers of CD3+- and CD4+- lymphocytes, normal range of CD8+- cells and lymphokin-producing capacity of leucocytes and decrease of immunoregulatory index. PMID- 27661288 TI - Intimate Partner Violence is Associated with Voluntary Sterilization in Women. AB - BACKGROUND: Intimate partner violence (IPV) may interfere with women's use of preferred forms of contraception, resulting in unwanted pregnancies forcing women to seek permanent sterilization. A history of child sexual abuse (CSA) presages the risk for IPV in adulthood setting the stage for adverse reproductive outcomes. OBJECTIVE: To determine whether CSA and IPV are associated with women's voluntary sterilization when adjusting for demographics and reproductive health history. METHODS: This cross-sectional study is based on in-person interviews of women (N = 278) drawn from outpatients surveyed in more than 10 different clinics (N = 2465). Women's history of gender-based violence and bilateral tubal ligation (BTL) were assessed. RESULTS: About half of the women had a past history of IPV and 29% disclosed CSA. CSA predicted later entry into an abusive relationship (odds ratio [OR] = 6.7). Sterilization was reported by 19.6%. Parity (3+ children), having had an abortion, and receipt of welfare were associated with sterilization in univariate tests. Among those women receiving a BTL, 74% had violent partners. Adjusted multivariate logistic regressions, adjusted for demographics and reproductive history, indicated that having had an abusive partner increased the odds of sterilization; parity was also highly associated. CSA exerted only an indirect influence on sterilization via entry into violent relationships. CONCLUSION: IPV raises the likelihood that women will choose sterilization. Despite the importance of women's access to permanent contraception, priority should be given to screening for gender-based violence and promoting interventions. PMID- 27661287 TI - Repairing tRNA termini: News from the 3' end. AB - The removal of transcriptional 5' and 3' extensions is an essential step in tRNA biogenesis. In some bacteria, tRNA 5'- and 3'-end maturation require no further steps, because all their genes encode the full tRNA sequence. Often however, the ends are incomplete, and additional maturation, repair or editing steps are needed. In all Eukarya, but also many Archaea and Bacteria, e.g., the universal 3'-terminal CCA is not encoded and has to be added by the CCA-adding enzyme. Apart from such widespread "repair/maturation" processes, tRNA genes in some cases apparently cannot give rise to intact, functional tRNA molecules without further, more specific end repair or editing. Interestingly, the responsible enzymes as far as identified appear to be polymerases usually involved in regular tRNA repair after damage. Alternatively, enzymes are recruited from other non tRNA pathways; e.g., in animal mitochondria, poly(A) polymerase plays a crucial role in the 3'-end repair/editing of tRNAs. While these repair/editing pathways apparently allowed peculiar tRNA-gene overlaps or mismatching mutations in the acceptor stem to become genetically fixed in some present-day organisms, they may have also driven some global changes in tRNA maturation on a greater evolutionary scale. PMID- 27661290 TI - A Phenotypic High-Content Screening Assay to Identify Regulators of Membrane Protein Localization. AB - Correct subcellular localization of proteins is a requirement for appropriate function. This is especially true in epithelial cells, which rely on the precise localization of a diverse array of epithelial polarity and cellular adhesion proteins. Loss of cell polarity and adhesion is a hallmark of cancer, and mislocalization of core polarity proteins, such as Scribble, is observed in a range of human epithelial tumors and is prognostic of poor survival. Despite this, little is known about how Scribble membrane localization is regulated. Here, we describe the development and application of a phenotypic high-content screening assay that is designed to specifically quantify membrane levels of Scribble to identify regulators of its membrane localization. A screening platform that is capable of resolving individual cells and quantifying membrane protein localization in confluent epithelial monolayers was developed by using the cytoplasm-to-cell-membrane bioapplication integrated with the Cellomics ArrayScan high-content imaging platform. Application of this method to a boutique human epithelial polarity and signaling small interfering RNA (siRNA) library resulted in highly robust coefficient-of-variance and Z' factor values. As proof of concept, we present two candidate genes whose depletion specifically reduces Scribble protein levels at the membrane. Data mining revealed that these proteins interact with components of the Scribble polarity complex, providing support for the utility of the screening approach. This method is broadly applicable to genome-wide and large-scale compound screening of membrane-bound proteins, and when coupled with pathway analysis the dataset becomes even more valuable and can provide predictive mechanistic insight. PMID- 27661289 TI - Validating a Hazardous Drinking Index in a Sample of Sexual Minority Women: Reliability, Validity, and Predictive Accuracy. AB - BACKGROUND: Although sexual minority women (SMW) are at increased risk of hazardous drinking (HD), efforts to validate HD measures have yet to focus on this population. OBJECTIVES: Validation of a 13-item Hazardous Drinking Index (HDI) in a large sample of SMW. METHODS: Data were from 700 adult SMW (age 18-82) enrolled in the Chicago Health and Life Experiences of Women study. Criterion measures included counts of depressive symptoms and post-traumatic stress disorder (PTSD) symptoms, average daily and 30-day ethanol consumption, risky sexual behavior, and Diagnostic and Statistical Manual (DSM-IV) measures of alcohol abuse/dependence. Analyses included assessment of internal consistency, construction of receiver operating characteristic (ROC) curves to predict alcohol abuse/dependence, and correlations between HDI and criterion measures. We compared the psychometric properties (diagnostic accuracy and correlates of hazardous drinking) of the HDI to the commonly used CAGE instrument. RESULTS: KR 20 reliability for the HDI was 0.80, compared to 0.74 for the CAGE. Predictive accuracy, as measured by the area under the receiver operating characteristic curve for alcohol abuse/dependence, was HDI: 0.89; CAGE: 0.84. The HDI evidenced the best predictive efficacy and tradeoff between sensitivity and specificity. Results supported the concurrent validity of the HDI measure. CONCLUSIONS: The Hazardous Drinking Index is a reliable and valid measure of hazardous drinking for sexual minority women. PMID- 27661294 TI - ? AB - So much has happened since the last edition of the newsletter that it is difficult to know which event has caused the most excitement: celebrating the success of the first QUAN conference in July, or reflecting on the interest shown at the International Society for Quality Assurance conference in Washington in the work nurses are doing in this country on quality, or enjoying the challenging questions hurled at us by delegates about our auditing and evaluation courses. PMID- 27661291 TI - How Are Information Seeking, Scanning, and Processing Related to Beliefs About the Roles of Genetics and Behavior in Cancer Causation? AB - Understanding that cancer is caused by both genetic and behavioral risk factors is an important component of genomic literacy. However, a considerable percentage of people in the United States do not endorse such multifactorial beliefs. Using nationally representative cross-sectional data from the U.S. Health Information National Trends Survey (N = 2,529), we examined how information seeking, information scanning, and key information-processing characteristics were associated with endorsing a multifactorial model of cancer causation. Multifactorial beliefs about cancer were more common among respondents who engaged in cancer information scanning (p = .001), were motivated to process health information (p = .005), and reported a family history of cancer (p = .0002). Respondents who reported having previous negative information-seeking experiences had lower odds of endorsing multifactorial beliefs (p = .01). Multifactorial beliefs were not associated with cancer information seeking, trusting cancer information obtained from the Internet, trusting cancer information from a physician, self-efficacy for obtaining cancer information, numeracy, or being aware of direct-to-consumer genetic testing (ps > .05). Gaining additional understanding of how people access, process, and use health information will be critical for the continued development and dissemination of effective health communication interventions and for the further translation of genomics research to public health and clinical practice. PMID- 27661295 TI - Quality conference. AB - The first QUAN conference was opened by Baroness Jean MacFarlane, who headed the first Standards of Nursing Care Project at the Royal College of Nursing in 1965. PMID- 27661292 TI - Interrelationship between 3,5,3'-triiodothyronine and the circadian clock in the rodent heart. AB - Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day (TOD)-dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, oscillations in T3 sensitivity in the heart is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by real-time quantitative polymerase chain reaction (qPCR). Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clock mutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2 and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g. Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes was interrogated at 3-h intervals over the subsequent 24-h period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed TOD-dependent sensitivity to T3 in the heart and its effects in the circadian clock genes expression. PMID- 27661293 TI - Examining the Construct Validity of the MMPI-2-RF Interpersonal Functioning Scales Using the Computerized Adaptive Test of Personality Disorder as a Comparative Framework. AB - This study aimed to examine the construct validity of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) interpersonal functioning scales (Ben-Porath & Tellegen, 2008/2011 ) using as a criterion measure the Computerized Adaptive Test of Personality Disorder-Static Form (CAT-PD-SF; Simms et al., 2011 ). Participants were college students (n = 98) recruited through the university subject pool. A series of a priori hypotheses were developed for each of the 6 interpersonal functioning scales of the MMPI-2-RF, expressed as predicted correlations with construct-relevant CAT-PD-SF scales. Of the 27 specific predictions, 21 were supported by substantial (>= |.30|) correlations. The MMPI-2-RF Family Problems scale (FML) demonstrated the strongest correlations with CAT-PD-SF scales Anhedonia and Mistrust; Cynicism (RC3) was most highly correlated with Mistrust and Norm Violation; Interpersonal Passivity (IPP) was most highly correlated with Domineering and Rudeness; Social Avoidance (SAV) was most highly correlated with Social Withdrawal and Anhedonia; Shyness (SHY) was most highly correlated with Social Withdrawal and Anxioiusness; and Disaffiliativeness (DSF) was most highly correlated with Emotional Detachment and Mistrust. Results are largely consistent with hypotheses suggesting support for both models of constructs relevant to interpersonal functioning. Future research designed to more precisely differentiate Social Avoidance (SAV) and Shyness (SHY) is suggested. PMID- 27661296 TI - Caines should resign. AB - Eric Caines is a civil servant. As the NHS Personnel Director he is appointed by the Secretary of State for Health, William Waldegrave. Yet it appears that Mr Caines is at liberty to dictate the future of the Review Body on pay and to plan for the devolution of Whitley authority in flagrant opposition to the Health Secretary's declared commitment to safeguard their future. PMID- 27661297 TI - UKCC. AB - Proposed legislation due to be launched this week will give the UKCC new powers to suspend practitioners from the register or issue a formal caution when misconduct has been proved but the offence is not deemed serious enough to warrant removal from the register. PMID- 27661298 TI - UKCC community nurse proposals. AB - Proposals for the new generic community nurse were launched for consultation yesterday by the UKCC. PMID- 27661300 TI - Scottish Charter ignores 'named nurses'. AB - Scotland's Patient's Charter launched last week contains no detail of the Prime Minister's 'named nurse' initiative, the Scottish Office has confirmed. PMID- 27661299 TI - Caines: 'Back him or sack him' call. AB - NHS Personnel Director Eric Caines is secretly hurrying to scupper the nurses' pay Review Body, despite Government pledges to keep it, leaked documents revealed last week. PMID- 27661301 TI - Grants increased by 50% but without ringfencing. AB - Health Secretary William Waldegrave last week announced a 50 per cent increase in specific grants to local authorities for AIDS, mental illness, alcohol and drug misuse work. PMID- 27661302 TI - ? AB - Image busting: A scene from the Department of Health's 60-second television commercial aimed at ensuring long-term nurse recruitment. The campaign also targets some of the negative stereotypes of nursing. PMID- 27661303 TI - Recruitment drive aims to improve public image. AB - The Department of Health last week launched a L2.6 million advertising campaign aimed at guaranteeing nurse recruitment into the next decade and aiming to improve the profession's public profile. PMID- 27661305 TI - Unions to debate pay and posts issues. AB - Irish nurses will meet this week at the Annual Delegate Conference of the country's largest nursing union to debate the major issues affecting the profession. PMID- 27661306 TI - Call for in-depth school counselling. AB - Education about sex and AIDS cannot be left to school nurses, an HIV/AIDS nurse counsellor said last week. PMID- 27661307 TI - ? AB - The Teikyo School UK team took part in the recent British Red Cross Walkathon, which coincided with the Japanese Matsuri Fair in London's Hyde Park. PMID- 27661308 TI - Government should not abdicate duty, says RCN. AB - Individuals cannot be expected to take full responsibility for health as some are in a better position to do so than others, RCN general secretary Christine Hancock said last week. PMID- 27661309 TI - Opposition plans for care grants outlined. AB - Shadow Health Minister Robin Cook pledged that an incoming Labour Government would provide ringfenced money to enable care in the community to be properly funded. But he said it was now too late to bring implementation forward from 1993, even if there were an election in November. PMID- 27661310 TI - ? AB - Health Minister Virginia Bottomley is pictured with Eleanor Lyons at the launch of the Working Mothers Association's Working Parents Handbooklast week. The book is available from WMA, 77 Holloway Road, London N7 8JZ. Price L4.50. PMID- 27661313 TI - Nursing update. AB - The RCN Nursing Update pilot programme which was broadcast on BBC1 last week is to be repeated on Friday at 1.15am. It lasts for an hour. RCN Nursing Update is a continuing education project devised by the RCN's Institute of Advanced Nursing Education. Accompanying supplements are published in Nursing Standard. PMID- 27661311 TI - 'Messy divide' between nursing and social care. AB - Nurses are under enormous pressure because of the 'messy' divide between health and social care, Janice Robinson, Director of the King's Fund Centre Carers' Unit, told the annual Social Services Conference. PMID- 27661314 TI - Schools blamed for lack of interest in nursing. AB - Only 3 per cent of girls in a Liverpool survey expressed an interest in becoming nurses, an RCN careers conference was told last week. PMID- 27661315 TI - Problems of elderly written off, says Anchor. AB - Older people's housing and social problems are being written off as the natural accompaniment of advancing years, the housing and care agency for the elderly, Anchor, claimed last week. PMID- 27661316 TI - Green light for HIV-infected staff. AB - Health workers with HIV should continue to practice, provided they conform to universal precautions and avoid invasive procedures, the International Council of Nurses has ruled. PMID- 27661318 TI - ? AB - Health visitors took their message to shoppers in Harrow recently as part of National Health Visitors' Week. PMID- 27661317 TI - NAHAT warns of NHS capital charge losses. AB - Money set aside for capital charges under the health service reforms could leak away from NHS providers if purchasers buy services from the private sector, a National Association of Health Authorities and Trusts research paper argues. PMID- 27661319 TI - Parliament. AB - Labour claims it will scrap all legal gags preventing nurses voicing their concerns about the health services in public. PMID- 27661322 TI - Network news. AB - Members of the Standards of Care project the QUAN Steering Group attended International Symposium on Quality in Washington DC in May. were given by June Girvin and Dunn about the use of the Dynamic Standard Setting System (DySSSy) by and by the research team from DySSSy' project which looks at the effect that standard setting has on patient care. Poster presentations were also presented on the work looking at classification systems by Anita McBride, and on the Standard Setting System by Sophie Hyndman and Gill Harvey, which scooped a prize for best poster. Interest in project was lively with a focus on the approach taken by DySSSy. For a full report see the article by Anita on page 11 . PMID- 27661323 TI - World news. AB - Montana The case of six hospice nurses facing misconduct charges for keeping pain relief drugs in an unlocked drawer has sparked national controversy over the demands of drug control versus the exigencies of pain control. PMID- 27661324 TI - ? AB - Great minds: Royal College of Nursing Newcastle Branch Secretary Pat Botterill cuts the cake at a party to celebrate the College's 75th anniversary, while (left) members of Tower Hamlets Branch in London prepare to do the honours at a party which followed a study session on quality. PMID- 27661325 TI - Low teaching priority for pressure area care. AB - Pressure area care receives a low priority in schools of nursing and continuing education departments, it was claimed recently. PMID- 27661326 TI - Exercise helps prevent childhood hypertension. AB - Physical training lowers blood pressure, helps prevent hypertension and improves overall fitness in children, a new study from Denmark has shown. PMID- 27661327 TI - Chest disease 'linked with low birth weight'. AB - Babies born below normal weight are more likely to suffer chest diseases in their first year and therefore more likely to suffer or even the from chronic obstructive airways disease in adult life, according to a new study. PMID- 27661329 TI - ? AB - Fit for life: Children can achieve general fitness and help prevent hypertension using ordinary school facilities, say Danish researchers. PMID- 27661328 TI - Psychosocial status 'is no recovery predictor'. AB - New research has challenged the belief that psychosocial factors may influence the rate of recovery from post-traumatic disorders. PMID- 27661330 TI - Routine toxoplasma tests advised against. AB - Patients with a clinical diagnosis of glandular fever but a negative Paul- Bunnell test should not be tested routinely for toxoplasmosis. PMID- 27661331 TI - Laparoscope instead of open appendicectomy? AB - A laparoscopic technique for appendicectomy might be a useful alternative to an open procedure. PMID- 27661333 TI - Could green tea prevent cancer? AB - Green tea, a traditional Japanese drink, might have anticancer properties. PMID- 27661332 TI - Identification model helps abused women. AB - Hospitals could do much to identify and help abused women using a model developed in the United States. PMID- 27661334 TI - Suspect osteomyelitis in diabetic foot ulcers. AB - The majority of diabetic foot ulcers have an underlying osteomyelitis which is clinically unsuspected. PMID- 27661335 TI - Ten commitments. AB - The Prime Minister's vision for tomorrow's NHS includes an enhanced role for nurses and greater recognition of their importance in health care, the profession was assured last month. PMID- 27661336 TI - Leaking the bad news. AB - Despite the headline-hitting swathe of traditional budget crises that have stricken NHS Trusts since April, we have been experiencing a false lull in the war over the future of the health service's workers. PMID- 27661337 TI - Would you Trust the doctor's regime? AB - Since April, Dr Mark Baker, Chief Executive of Bradford Hospitals Trust, has axed 10 per cent of his beds, come under fire from the House of Commons Health Committee, and become a prime target for local and national media. He says he is having fun. PMID- 27661339 TI - UKCC code only for discipline? AB - I am worried about the apparent lack of support from the United Kingdom Central Council for nurses such as Graham Pink, following a number of recent cases involving whistleblowers facing disciplinary penalties that have been reported in the national press. PMID- 27661340 TI - Funding needed for whistleblowers. AB - It appears that the reward one gets for airing one's conscience in the field of nursing is the sack. PMID- 27661338 TI - A feminist sold short. AB - Throughout her parliamentary career Clare Short, opposition spokesperson on Social Security until her resignation earlier this year, has been an unequivocal advocate of women's rights. PMID- 27661341 TI - Casualty Update. AB - Last week's Casualty saw some dangerous games played out. The most obvious game was macho man being drawn into the deep end of the noisy, crowded swimming pool. The dangers were clear. Who can tell the screams of fun from those of fear? PMID- 27661342 TI - RCN out of step in childcare. AB - I read with interest Linda Nazarko and Sharon McVey's recent articles on the problems of childcare for working student parents and trained staff (Nursery Crimes, Nursing Standard September 18 and Shift Those Patterns, Tradimus August 14). PMID- 27661343 TI - More praise for award winner. AB - I was very pleased to read of Elizabeth Hopper's Nursing Standard BUPA Nursing Nurse 91 Award for her work in bereavement and loss during or after pregnancy (Nursing Standard September 18). PMID- 27661344 TI - Information exchange. AB - I am doing a national survey of community psychiatric nurses currently involved in forensic psychiatry. PMID- 27661346 TI - Nurse 91 Awards. PMID- 27661345 TI - Gossip. AB - In among the recent spate of stories concerning the imminent threat of seeing hospitals in the hands of the receivers has come a story about receivers in the hands of hospitals. PMID- 27661347 TI - Health promotion Health promotion , 2nd edition Edelman C and handle C C V Mosby 616pp L27.95 0-8016-3260-9 [Formula: see text]. AB - The second edition of Health Promotion: Throughout the Lifespan should, I hope, gain a wider readership than anticipated, given the emphasis on health promotion in the general practitioner contracts and the expansion of health promotion activities in hospitals and the community. All nurses have an important part to play in health promotion, and this book has something to offer everyone, regardless of discipline, background or place of work. PMID- 27661348 TI - Essentials of Human Anatomy and Physiology, 3rd edition Essentials of Human Anatomy and Physiology, 3rd edition Marieb E N Cummings 480pp L29.95 0-8053-4804 2 [Formula: see text]. AB - Anatomy and physiology is a subject about which few wax lyrical. Elaine Marieb's delightful text proves to be the exception to the rule. Clearly written for those will little background knowledge in the workings of the human body, it gently explores the body in 16 systems-based, self-contained chapters. PMID- 27661349 TI - Child Abuse Johnson P Child Abuse Crowood Press 272pp L9.50 1-85223-360-5 [Formula: see text]. AB - Paul Johnson is a social worker with extensive experience in the field of child protection. In Child Abuse - Understanding theProblem, he carefully and successfully reveals the whole subject of child abuse, dealing with controversies, definition difficulties, different areas of child abuse, legal and local authority procedures, investigations and, refreshingly, treatment issues. PMID- 27661350 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Jo Barr, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX (Fax 081-423 3867). PMID- 27661351 TI - Behavioral regulations and dispositional flow in exercise among American college students relative to stages of change and gender. AB - OBJECTIVE: The purpose of this study was to examine behavioral regulations and dispositional flow in exercise among university students in terms of gender and stage of change. PARTICIPANTS: Data were collected from American college students (N = 257; Mage +/- SD = 23.02 +/- 4.05) in Spring 2013. METHODS: Behavioral regulations and dispositional flow in exercise were assessed, along with stage of change. RESULTS: Exercisers in the maintenance stage of change displayed significantly more self-determined motivation to exercise and a greater tendency to experience flow than those in preparation and action stages. Significant correlations were observed among behavioral regulations and flow state. Nonsignificant differences were observed for gender on behavioral regulations and dispositional flow in exercise. CONCLUSIONS: The results suggest that promotion of self-determined motivation and dispositional flow in exercisers may improve the quality of their experiences, as well as to foster their exercise behavior. PMID- 27661352 TI - High sensitivity and resolution integrated optical system for portable Raman spectrometer. AB - An integrated optical system with high sensitivity and resolution was presented. This was made possible by coupling a probe to a monochromator directly, using an aspheric lens and an achromatic lens in the coupling path, using a dichroic filter with high transmission and a steep transitional zone as a beam splitter, increasing the throughput of the monochromator, and optimizing its structural parameters. This optical system has a high sensitivity; the tested spectrogram of a glass rod demonstrated that the signal-to-noise ratio measured by the integrated optical system was almost 4 times as high as an independent probe and monochromator. The optical system also has the advantages of high resolution (4 cm-1 or 0.28 nm), low cost, and portable size. This work lays a good groundwork for the development of a high sensitivity, high resolution, and low cost integrated portable Raman spectrometer. PMID- 27661353 TI - Study on intelligent recognition detection technology of debond defects for ceramic matrix composites based on terahertz time domain spectroscopy. AB - With the wide use of high-temperature-resistant ceramic matrix composites (CMCs) in aviation and space flight, it is important to detect the quality of the bonding. This paper used terahertz (THz) time-domain spectroscopy nondestructive testing technology to inspect the bonding defects of the CMC. This paper puts forward a method-extraction method, which is applied to make samples to simulate the bonding defect of CMC by embedding polytetrafluoroethylene (PTFE) sheets with 0.12 mm thickness into the adhesive layer and extracting it after curing and presetting the bonding defects. On the basis of the classical and analytical algorithms, such as the maximum in time-domain and power spectrum integration, through further study in the THz spectral characteristics of bonding samples for CMC, we specifically introduce the upper debond coefficient, lower debond coefficient, average absorption coefficient for the frequency domain, centroid coefficient for the frequency domain, and other characteristics. By optimizing the THz detection characteristics set, as a sample, we adopt the neural network intelligent recognition algorithm to detect the upper and lower debond defects in samples and realize the intelligent identification for CMC debond defects. PMID- 27661354 TI - High-resolution, dual-depth spectral-domain optical coherence tomography with interlaced detection for whole-eye imaging. AB - Dual-depth spectral-domain optical coherence tomography (SD-OCT) enables high resolution in vivo whole-eye imaging. Two orthogonally polarized beams from a source are focused simultaneously on two axial positions of the anterior segment and the retina. For the detector arm, a 1*2 ultrafast optical switch sequentially delivers two spectral interference signals to a single spectrometer, which extends the in-air axial depth range up to 9.44 mm. An off-pivot complex conjugate removal technique doubles the depth range for all anterior segment imaging. The graphics-processing-unit-based parallel signal processing algorithm supports fast two- and three-dimensional image displays. The obtained high resolution anterior and retinal images are measured biometrically. The dual-depth SD-OCT system has an axial resolution of ~6.4 MUm in air, and the sensitivity is 91.79 dB at 150 MUm from the zero-delay line. PMID- 27661355 TI - Array illumination of a Fresnel-Dammann zone plate. AB - The traditional Dammann grating is a phase-only modulation, and its theoretical foundation is based on far-field diffraction. Here we extend the traditional Fresnel zone plate (FZP) into a Fresnel-Dammann zone plate (FDZP), which is, in essence, considered as a FZP with Dammann modulation. Different from the Dammann grating, a single FDZP can generate array illumination from the near field to the far field by means of amplitude-only modulation in the absence of phase modulation. We then give some array illuminations operated in a water window to validate the feasibility and validity. This kind of wave-front modulation technology can be applied to array focusing and imaging from the x-ray to the EUV region. PMID- 27661356 TI - Harmonics analysis of the photonic time stretch system. AB - Photonic time stretch (PTS) has been intensively investigated in recent decades due to its potential application to ultra-wideband analog-to-digital conversion. A high-speed analog signal can be captured by an electronic analog-to-digital converter (ADC) with the help of the PTS technique, which slows down the speed of signal in the photonic domain. Unfortunately, the process of the time stretch is not linear due to the nonlinear modulation of the electro-optic intensity modulator in the PTS system, which means the undesired harmonics distortion. In this paper, we present an exact analytical model to fully characterize the harmonics generation in the PTS systems for the first time, to the best of our knowledge. We obtain concise and closed-form expressions for all harmonics of the PTS system with either a single-arm Mach-Zehnder modulator (MZM) or a push-pull MZM. The presented model can largely simplify the PTS system design and the system parameters estimation, such as system bandwidth, harmonics power, time bandwidth product, and dynamic range. The correctness of the mathematic model is verified by the numerical and experimental results. PMID- 27661357 TI - Model-based restoration using light vein for range-gated imaging systems. AB - The images captured by an airborne range-gated imaging system are degraded by many factors, such as light scattering, noise, defocus of the optical system, atmospheric disturbances, platform vibrations, and so on. The characteristics of low illumination, few details, and high noise make the state-of-the-art restoration method fail. In this paper, we present a restoration method especially for range-gated imaging systems. The degradation process is divided into two parts: the static part and the dynamic part. For the static part, we establish the physical model of the imaging system according to the laser transmission theory, and estimate the static point spread function (PSF). For the dynamic part, a so-called light vein feature extraction method is presented to estimate the fuzzy parameter of the atmospheric disturbance and platform movement, which make contributions to the dynamic PSF. Finally, combined with the static and dynamic PSF, an iterative updating framework is used to restore the image. Compared with the state-of-the-art methods, the proposed method can effectively suppress ringing artifacts and achieve better performance in a range gated imaging system. PMID- 27661358 TI - Non-uniformity correction for division of focal plane polarimeters with a calibration method. AB - Division of focal plane polarimeters are composed of nanometer polarization elements overlaid upon a focal plane array (FPA) sensor. The manufacturing flaws of the polarization grating and each detector in the FPA having a different photo response can introduce non-uniformity errors when reconstructing the polarization image without correction. A new calibration method is proposed to mitigate non uniformity errors in the visible waveband. We correct non-uniformity in the form of a vector. The correction matrix and offset vector are calculated for the following correction. The performance of the proposed method is compared with state-of-the-art techniques by employing simulated data and real scenes. The experimental results showed that the proposed method can effectively mitigate non uniformity errors and achieve better visual results. PMID- 27661359 TI - Optical amplification and reshaping based on the Peregrine rogue wave. AB - Based on the characteristics of the Peregrine rogue wave, the amplification and the reshaping of solitons are investigated. The numerical results show that the amplification and the reshaping of solitons can be realized by injecting a continuous wave (CW) and filtering the CW at suitable positions. The combination of a continuous-wave pump and a spectral filter placed suitably in fiber plays the role of the amplifier, which can be used to long-haul the transmission of solitons. As an example, a long-haul transmission with four amplification periods is demonstrated. PMID- 27661360 TI - Optofluidic two-dimensional grating volume refractive index sensor. AB - We present an optofluidic reservoir with a two-dimensional grating for a lab-on-a chip volume refractive index sensor. The observed diffraction pattern from the device resembles the analytically obtained fringe pattern. The change in the diffraction pattern has been monitored in the far-field for fluids with different refractive indices. Reliable measurements of refractive index variations, with an accuracy of 6*10-3 refractive index units, for different fluids establishes the optofluidic device as a potential on-chip tool for monitoring dynamic refractive index changes. PMID- 27661361 TI - Systematic afterpulsing-estimation algorithms for gated avalanche photodiodes. AB - We present a method designed to efficiently extract optical signals from InGaAs avalanche photodiodes (APDs) operated in gated mode. In particular, our method permits an estimation of the fraction of counts that actually results from the signal being measured, as opposed to being produced by noise mechanisms, specifically by afterpulsing. Our method in principle allows the use of InGaAs APDs at high detection efficiencies, with the full operation bandwidth, either with or without resorting to the application of a dead-time. As we show below, our method can be used in configurations where afterpulsing exceeds the genuine signal by orders of magnitude, even near saturation. The algorithms that we have developed are suitable to be used either in real-time processing of raw detection probabilities or in post-processing applications, after a calibration step has been performed. The algorithms that we propose here can complement technologies designed for the reduction of afterpulsing. PMID- 27661362 TI - Traceability of solar UV measurements using the Qasume reference spectroradiometer. AB - One major objective of the European Joint Research Project "Traceability for surface spectral solar ultraviolet (UV) radiation" was to reduce the uncertainty of spectral UV measurements. The measurement instrument used for this work was the portable UV European reference spectroradiometer Qasume. The calibration uncertainty of this instrument was decreased and validated by a comparison of direct calibrations against a primary standard for spectral irradiance, a high temperature blackbody radiator, and against a reference detector using a spectrally tunable laser as a monochromatic source. The spectral irradiance responsivity of the reference detector is traceable to the primary standard of optical power, realized through a cryogenic radiometer, and to the SI unit of meter. The measuring technique was improved by the construction of a new reference spectroradiometer, QasumeII. An improved input optics removes the dependences of the measured solar irradiance on the angle of incident for solar zenith angle smaller than 75 deg. Moreover, a hybrid photon detection system enables continuous tracking of the instrument's responsivity changes. For both spectroradiometer systems an uncertainty budget was calculated. The improvements have reduced the measurement uncertainties of solar spectral UV irradiance measurements from 4.8% in 2005 to 2.0% (k=2) in the spectral region above 310 nm. The largest sources of uncertainty were the absolute spectral irradiance responsivity calibration, the angular response uncertainty, and the instrument stability using the hybrid detector, which were reduced from 3.6% to 1.1%, from 1.2% to 0.6%, and from 0.65% to 0.4%, with respect to the situation prior to the project. The new instrument was validated during a four month intercomparison relative to the Qasume reference. The mean ratio of the solar irradiance scans between the two reference spectroradiometers has an offset of +0.7% and a standard deviation of +/-1.5% for a wavelength greater than 305 nm, which is well within the combined uncertainty of 3.7% calculated from the uncertainties of the two systems. PMID- 27661363 TI - Free space optical communications system performance under atmospheric scattering and turbulence for 850 and 1550 nm operation. AB - In this work, a free space optical communication (FSO) link is proposed and utilized to explore and evaluate the FSO link performance under the joint occurrence of the atmospheric scattering and turbulence phenomena for 850 and 1550 nm operation. Diffraction and nondiffraction-limited systems are presented and evaluated for both wavelengths' operation, considering far-field conditions under different link distances. Bit error rate, pointing error angles, beam divergence angles, and link distance are the main performance indicators that are used to evaluate and compare the link performance under different system configurations and atmospheric phenomena combinations. A detailed study is performed to provide the merits of this work. For both far-field diffraction limited and nondiffraction-limited systems, it is concluded that 1550 nm system operation is better than 850 nm for the whole presented joint occurrences of atmospheric scattering and turbulence. PMID- 27661364 TI - Dual-wavelength common-path digital holographic microscopy for quantitative phase imaging based on lateral shearing interferometry. AB - A dual-wavelength common-path digital holographic microscopy based on a single parallel glass plate is presented to achieve quantitative phase imaging, which combines the dual-wavelength technique with lateral shearing interferometry. Two illumination laser beams with different wavelengths (lambda1=532 nm and lambda2=632.8 nm) are reflected by the front and back surfaces of the parallel glass plate to create the lateral shear and form the digital hologram, and then the hologram is reconstructed to obtain the phase distribution with a synthetic wavelength Lambda=3339.8 nm. The experimental configuration is very compact, with the advantages of vibration resistance and measurement range extension. The experimental results of the laser-ablated pit, groove, and staircase specimens show the feasibility of the proposed configuration. PMID- 27661365 TI - Simulation study of dual-space microscopy. AB - We explore the convergence of the dual-space microscopy (DSM) phase-recovery algorithm. DSM is an optical microscopy technique based on simultaneous observation of an object in the position and momentum spaces. We present one dimensional (1D) simulations of this technique, demonstrating that the DSM technique is capable to resolve periodic and nonperiodic structures with a resolution well below the Rayleigh resolution limit. Using a simple and faster 1D version of the full 2D DSM algorithm, we simulated the DSM technique for thousands of different samples. Our results demonstrate that the DSM algorithm always converges rapidly to the correct optical disturbance. PMID- 27661366 TI - Measurement of reflection phase using thick-gap Fabry-Perot etalon. AB - We report measurement of the reflection phase of a dielectric (glass)/titanium (Ti) surface in the visible wavelength using a thick-gap Fabry-Perot (FP) interferometry technique. Using a two-beam interference model for the reflection peaks and troughs of the FP etalon, we obtain the air-gap spacing of the etalon and, more importantly, the reflection phase of the etalon substrate. We find systematic dependence of the as-measured reflection phase on the air-gap spacing due to the numerical aperture effect of the measuring objective. However, the relative reflection phase of Ti with respect to glass is independent of the air gap spacing. As a demonstration of our approach in the optical characterization of small metamaterial samples, we also measure the reflection phase of a micron sized 2D Au sawtooth nanoarray. The experiment is in good agreement with the model simulation. PMID- 27661367 TI - Integrated backlight module to provide a collimated and uniform planar light source. AB - We report a novel integrated backlight module (IBLM), which is composed of a compound optical film (COF) and a light guide plate (LGP) without any microstructure. The COF proposed in the paper comprises functions of a conventional microstructure that adjusts the emergent light and two cross brightness enhancement films (BEF). The four surfaces of the LGP are coated with highly reflective film. The COF can not only adjust the distribution of the output light by varying the density of the microstructure on the COF, but also can collimate the two cross-direction lights into the normal direction. The horizontal and vertical full width at half maxima of angular intensity of the IBLM with the proposed COF for the optimum are of 14 and 24 deg, respectively. The spatial uniformity and total optical efficiency of the IBLM have reached 85% and 77.2%, respectively. The optical efficiency has been increased by 1.3 times and the on-axis luminance has improved by 5.1 times by using a backlight module (BLM) with the COF, in comparison with the conventional edge-lit BLM that we researched [Appl. Opt.55, 1494 (2016)APOPAI0003-693510.1364/AO.55.001494]. Most importantly, the COF only needs to be configured with a relatively low-cost and easily-manufactured LGP; therefore, the BLM with the adopted COF can be further developed for large-sized application. PMID- 27661368 TI - Foveated scanning: dynamic monodimensional enlargement of resolved field of view in lenses of scanner systems. AB - An inconsistency between the circular symmetric geometry of conventional optical imagers and the geometry of long linear sensors used in today's line-scan cameras results in suboptimal separate design of optics and electronics of scanner systems. Based on the method of foveated optical imaging, a technique named foveated scanning (FS) is proposed in this paper. The FS technique is employed to enlarge the one-dimensional resolved field of view (RFOV) of conventional lenses and permits optimized performance on a line-of-interest in the image plane where the optoelectronic sensor is located. The achieved enlargement of RFOV is verified on a proof-of-concept basic telephoto lens. Both modulation transfer function analysis and the imaging simulation of a standard target have been performed. Results show a twofold increase in RFOV by this technique. PMID- 27661369 TI - Noise in adaptive interferometric fiber sensor based on population dynamic grating in erbium-doped fiber. AB - Experimental investigations of the main noise sources that limit the sensitivity of the adaptive interferometric all-fiber sensors operating in the communication wavelength region are reported. Adaptive properties (i.e., the autostabilization of an optimal operation point of the interferometer) are enabled by the dynamic population grating recorded in a segment of the erbium-doped fiber (EDF) at milliwatt-scale cw power in the 1480-1560 nm spectral range. The utilized symmetric Sagnac configuration with low light internal reflections ensures reduced sensitivity of the sensor to phase noise of the laser, while intensity noise is reduced to an insignificant level by the balanced detection scheme. It is shown that the fluorescence from the erbium ions, excited by the counterpropagating waves recording the grating, increases the noise level from the fundamental shot noise approximately by a factor of 2-3 only. It is also shown that conventional communication distributed feedback (DFB) semiconductor lasers with megahertz linewidth are not suitable for high-sensitivity applications of such sensors. Because of inevitable backreflections from the output terminal devices (photodiodes, insulators, circulator), the above mentioned fundamental noise level is increased by 2 orders of magnitude due to high phase noise of the DFB laser. PMID- 27661370 TI - Far-field characteristics of the square grooved-dielectric lens antenna for the terahertz band. AB - In order to improve the gain and directionality of a terahertz antenna, a square grooved-dielectric lens antenna based on a Fresnel zone plate is proposed. First, a diagonal horn, which is adopted as the primary feed antenna, is designed. Then, the far-field characteristics of the lens antenna are studied by using Fresnel Kirchhoff diffraction theory and the paraxial approximation. The effects of the full-wave period, the focus diameter ratio, the subregion, and the dielectric substrate thickness on radiation characteristics are studied. The experimental results show that the proposed lens antenna has axisymmetric radiation patterns. The gain is over 26.1 dB, and the 3 dB main lobe beam width is lower than 5.6 degrees across the operation band. The proposed lens antenna is qualified for applications in terahertz wireless communication systems. PMID- 27661371 TI - All-optical processes in double quantum dot structure. AB - The ladder-plus-Y double quantum dot structure was modeled for all-optical processing by combining the density matrix theory with the pulse width description of the applied pulse. The momentum matrix elements are calculated including the wetting layer. The ladder-plus-Y structure exhibits pattern-free output with high bit rate (50 Tbps), which is critical in optical communication applications. It is shown that very high ground-state occupation with periodic shape for state occupations is critical in obtaining a pattern-free eye diagram. PMID- 27661372 TI - Extending depth of field for hybrid imaging systems via the use of both dark and dot point spread functions. AB - In this paper, we propose one method based on the use of both dark and dot point spread functions (PSFs) to extend depth of field in hybrid imaging systems. Two different phase modulations of two phase masks are used to generate both dark and dot PSFs. The quartic phase mask (QPM) is used to generate the dot PSF. A combined phase mask between the QPM and the angle for generating the dark PSF is investigated. The simulation images show that the proposed method can produce superior imaging performance of hybrid imaging systems in extending the depth of field. PMID- 27661373 TI - Gold nanobipyramid Q-switched Nd:LGGG eye-safe laser operating at 1423.4 nm. AB - The performance of a laser-diode-pumped passively Q-switched Nd:LGGG laser at 1423.2 nm with gold nanobipyramids (Au-NBPs) as a saturable absorber was demonstrated. An average output power of 125 mW was obtained at a pump power of 12.2 W, corresponding to an optical-to-optical conversion efficiency of 1.36% and a slope efficiency of 1.78%. A minimum pulse width of 514 ns at a pulse repetition rate of 98.6 kHz was obtained at a pump power of 12.2 W. To the best of our knowledge, this is the first report focusing on the application of Au-NBPs as a saturable absorber for pulse laser operation in the eye-safe region. PMID- 27661374 TI - EXAFS studies on Gd-doped ZrO2 thin films deposited by RF magnetron sputtering. AB - ZrO2 thin films with 0%, 7%, 9%, 11%, and 13% Gd doping have been prepared by RF magnetron sputtering and have been characterized by grazing incidence x-ray diffraction, spectroscopic ellipsometry, and optical transmission measurements to probe their structural and optical properties. Extended x-ray absorption fine structure (EXAFS) measurements have also been carried out on the samples at the Zr K- and Gd L3-edges. It has been observed that Gd goes to Zr sites up to 9%-11% doping concentration, and for Gd doping concentrations beyond 11%, Gd precipitates out as a separate Gd2O3 phase. The local structure information surrounding the Zr and Gd sites obtained from the analysis of the EXAFS studies have also been used to explain the macroscopic optical properties of the samples. PMID- 27661375 TI - Thermal effects in the DKDP Pockels cells in the 215-300 K temperature range. AB - The thermal and electro-optical effects in Pockels cells with deuterated potassium dihydrogen phosphate (DKDP) crystals in the 215-300 K temperature range were investigated. Half-wave voltage decreases linearly with cooling, thereby it reduces seven times (up to 1 kW) with cooling to 215 K. The optical power of the thermally induced lens falls twice on cooling to 215 K from 300 K; thermally induced depolarization is almost independent of temperature and determined by input radiation power. A significant reduction of the thermally induced depolarization in a DKDP crystal with the axis inclined to the polarization plane of the beam was demonstrated numerically and experimentally. Thus, the DKDP crystals cooled to 215 K allow the creation of a low-voltage Pockels cell working with a high average and peak laser power. PMID- 27661376 TI - Colorless beat interference cancellation receiver for the orthogonally polarized SSB-OOFDM signal with reduced guard band. AB - In the paper, we have proposed a novel optical orthogonal frequency division multiplexing (OOFDM) link scheme with the colorless beat interference cancellation receiver (BICR) structure for the single-sideband OOFDM (SSB-OOFDM) signal with an orthogonally polarized optical carrier and sideband, which is generated by using a polarization modulator and an optical band-pass filter. The BICR, employing only a polarization beam splitter and a balanced photodiode pair, can colorlessly mitigate the signal-signal beat interference (SSBI) induced by the square-law detection in a photodiode and thus the spectral efficiency (SE) is improved by reducing the guard band (GB) between the optical carrier and OOFDM signal. A simulation link for the 40 Gbit/s 16-QAM SSB-OOFDM signal with a reduced GB is built to demonstrate the feasibility of our proposed scheme. The simulation results indicate that the link has a higher SE compared to the conventional intensity modulation and direction detection scheme and the BICR exhibits a better performance in suppressing SSBI according to the error vector magnitude and the constellation diagrams. PMID- 27661377 TI - Master/slave optical coherence tomography imaging of eyelid basal cell carcinoma. AB - Optical coherence tomography (OCT) is fast emerging as an additional non interventional modality for skin tumor detection and diagnosis. A master/slave flying spot OCT configuration was assembled to detect periocular basal cell carcinomas (BCC). A swept source at 1300 nm and sweeping speed of 50 kHz were used. A three-step process was involved. First, 384 channeled spectra using a mirror were stored for 384 optical path differences at the master stage. Then, the stored channeled spectra (masks) were correlated with the channeled spectrum from the BCC tissue to produce 384 en face OCT images (200*200 pixels) for the optical path difference values used to acquire the masks. Finally, these en face slices were stacked to form a volume to cross-reference BCC tumor margins in the orthogonal plane. Per each eyelid sample, several en face images of 200*200 lateral pixels are produced in the time to scan laterally a complete raster of 1.6 s. Combination of the en face views with the cross-sectioning views allow for better discrimination of BCCs comparable to using cross-sectional imaging alone, as previously reported using the conventional fast-Fourier-transform-based OCT techniques. PMID- 27661378 TI - Influence of the microstructure geometry of patterned sapphire substrates on the light extraction efficiency of GaN LEDs. AB - The influence of the microstructure geometry of patterned sapphire substrates (PSS) on the light extraction efficiency (LEE) of GaN light-emitting diodes (LEDs) is numerically analyzed. Cone structures of various dimensions are studied, along with dome and mixed microstructures. LEE is found to mainly depend on the microstructure surface slope. LEE rises quickly with slope and flattens out when the slope exceeds 0.6. Scaling down the microstructure has little effect on LEE. Light rays are found to travel longer distances in PSS LEDs, as compared with LEDs grown on a flat substrate. Keeping GaN absorption loss low is important for LEE optimization. PMID- 27661379 TI - Development of an optical microscopy system for automated bubble cloud analysis: publisher's note. AB - This note reports changes to the author list and additional funding sources for [Appl. Opt.55, 6102 (2016)].APOPAI0003-693510.1364/AO.55.006102. PMID- 27661380 TI - Spectral tuning of a locally bent microfiber taper interferometer with a nanosized liquid crystal overlay. AB - In this paper, the tuning characteristics of locally bent microfiber taper covered with a nanosized high-refractive-index liquid crystal (LC) layer under different temperatures and electric field intensities have been theoretically analyzed and experimentally investigated. A locally bent microfiber taper interferometer with a waist diameter of ~3.72 MUm is fabricated by using the flame brushing technique, followed by bending the transition region of the taper to form a modal interferometer and later by placing a ~200 nm LC layer over the uniform taper waist region. Experimental results indicate that a high-efficiency thermal or electric tuning of an LC-coated locally bent microfiber taper interferometer could be achieved. This suggests a potential application of this device as tunable all-fiber photonic devices, such as filters, modulators, and sensing elements. PMID- 27661381 TI - Architecture for one-shot compressive imaging using computer-generated holograms. AB - We propose a synchronous implementation of compressive imaging. This method is mathematically equivalent to prevailing sequential methods, but uses a static holographic optical element to create a spatially distributed spot array from which the image can be reconstructed with an instantaneous measurement. We present the holographic design requirements and demonstrate experimentally that the linear algebra of compressed imaging can be implemented with this technique. We believe this technique can be integrated with optical metasurfaces, which will allow the development of new compressive sensing methods. PMID- 27661382 TI - Laser-induced breakdown spectroscopy of liquid solutions: a comparative study on the forms of liquid surface and liquid aerosol. AB - Liquid surface and liquid aerosol as the traditional liquid forms for laser induced breakdown spectroscopy (LIBS) and inductively coupled plasma (ICP), respectively, have been used to analyze chromium (Cr) and cadmium (Cd) elements using LIBS in a liquid solution. The spectral differences, the effects of laser energy and laser frequency, the accumulated number of laser pulses, gate delay time, and the quantitative analyses for a liquid surface and a liquid aerosol were compared. The results showed that the liquid surface demonstrated a lower plasma threshold, higher optical emission intensity, and higher single-to-noise ratio. Moreover, the relative standard deviations (RSDs) of the intensities of the liquid aerosol are better than those of the liquid surface. Furthermore, the results of the quantitative analyses of Cr I 357.86 nm and Cd I 361.05 nm of the liquid surface are close to those of the liquid aerosol. The limit of detections of Cr and Cd of the liquid surface were 2.764 and 86.869 MUg/mL, which were close to those of liquid aerosol, 2.847 MUg/mL of Cr and 97.635 MUg/mL of Cd. For both the liquid surface and liquid aerosol, the coefficient of determination R2 of the calibration curve for Cr and Cd were above 0.99, and the average RSDs of Cr and Cd of the liquid surface were 0.027 and 0.054, which were similar to the 0.020 of Cr and 0.042 of Cd of the liquid aerosol. These results suggest that both the liquid surface and aerosol have similar detection abilities for water quality monitoring. PMID- 27661383 TI - Proximity operators for phase retrieval. AB - We present a new formulation of a family of proximity operators that generalize the projector step for phase retrieval. These proximity operators for noisy intensity measurements can replace the classical "noise-free" projection in any projection-based algorithm. They are derived from a maximum-likelihood formulation and admit closed form solutions for both the Gaussian and the Poisson cases. In addition, we extend these proximity operators to under-sampled intensity measurements. To assess their performance, these operators are exploited in a classical Gerchberg-Saxton algorithm. We present numerical experiments showing that the reconstructed complex amplitudes with these proximity operators always perform better than using the classical intensity projector, while their computational overhead is moderate. PMID- 27661384 TI - Characteristics of spectral lines with crater development during laser-induced breakdown spectroscopy. AB - To study the characteristics of spectral lines with crater development during laser-induced breakdown spectroscopy, the changes in the spectral line intensities of iron (Fe) and chromium (Cr) during the development of craters were investigated. Images of the plasmas formed during crater development were captured, and the temperatures and electron densities of the plasmas were calculated. The results showed that when a crater developed, the intensities of the ion lines decreased and the intensities of the atomic lines increased. This is because the plasmas generated in the crater have a higher initial emission intensity and experience more rapid cooling as the crater develops. These two effects lead to changes in the rates of decrease of ion and atomic line intensities over time. Therefore, the changes in intensities of ion lines caused by crater development differ from which of atomic lines. PMID- 27661385 TI - Error correction for rotationally asymmetric surface deviation testing based on rotational shears. AB - We present a practical method for absolute testing of rotationally asymmetric surface deviation based on rotation averaging, additional compensation, and azimuthal errors correction. The errors of angular orders kNtheta neglected in the traditional multiangle averaging method can be reconstructed and compensated with the help of least-squares fitting of Zernike polynomials by an additional rotation measurement with a suitable selection of rotation angles. The estimation algorithm adopts the least-squares technique to eliminate azimuthal errors caused by rotation inaccuracy. The unknown relative alignment of the measurements also can be estimated through the differences in measurement results at overlapping areas. The method proposed combines the advantages of the single-rotation and multiangle averaging methods and realizes a balance between the efficiency and accuracy of the measurements. Experimental results show that the method proposed can obtain high accuracy even with fewer rotation measurements. PMID- 27661386 TI - Focal length measurement based on Fresnel diffraction from a phase plate. AB - A method based on the Fresnel diffraction of light from the phase step is introduced for measuring effective focal length (EFL) and back focal length (BFL) of optical imaging systems. It is shown that, as a transparent plane-parallel plate is illuminated at a boundary region by a monochromatic beam of light, Fresnel diffraction occurs because of the abrupt change in phase imposed by the finite change in refractive index at the plate boundary. Variation of the incident angle in a convergent (or divergent) beam of light causes the periodic intensity along the central fringe of the diffraction pattern. The measurement of the extrema position of the intensity distribution accurately provides the EFL and BFL. The technique is easy to apply and can measure a wide range of both positive and negative focal lengths. The measuring setup can be very compact with low mechanical and optical noises. As examples of this technique, the EFLs of five different lenses are experimentally obtained. The results are quite consistent with the values indicated by the lens manufacturer. PMID- 27661387 TI - High-power and high-efficiency diode-pumped Nd:LuYAG mixed crystal lasers operating at 939 and 946 nm. AB - We report on high-performance infrared lasers at 0.94 MUm based on quasi-three level transition of F3/24->I9/24 in Nd:LuYAG mixed crystal, for the first time to our knowledge. The maximum output power was achieved to 5.64 W with slope efficiency of approximately 52.5% at 946 nm. The simultaneous dual-wavelength laser at 939 and 946 nm is also obtained with maximum output power of 3.61 W and slope efficiency of 34.8% by introducing a glass etalon into the cavity. Moreover, a 2.0-W single-wavelength laser at 939 nm can be further attained by suitably tilting the etalon. Using a Cr:YAG saturable absorber, Q switched laser operation is realized with maximum average output power of 0.68 W and the narrowest pulse width of 8.4 ns, which results in the maximum single pulse energy of approximately 55.3 MUJ and the maximum pulse peak power of approximately 6.15 kW. Finally, thermal focal length of the laser crystal is estimated by using a flat-flat laser cavity. PMID- 27661388 TI - The effect of chemical variations on the structural polarity of relaxor ferroelectrics studied by resonance Raman spectroscopy. AB - Resonance Raman spectroscopy was applied to doped PbSc0.5Ta0.5O3 and PbSc0.5Nb0.5O3 relaxor ferroelectrics, to better understand the effect of composition disorder on the mesoscopic-scale polar order in complex perovskite type (ABO3) ferroelectrics. The excitation photon energy used was 3.8 eV, which is slightly above the energy gap and corresponds to the maximum of the optical dielectric permittivity. Group-theory analysis reveals that the resonance Raman scattering (RRS) observed under these conditions is allowed only in polar crystal classes. Therefore, RRS is dominated by the atomic dynamics of nanoregions with coherent polar distortions, which considerably facilitates the comparison of polar order in various compounds. The results show that A-site doping (Ba(2+), Sr(2+), La(3+), Bi(3+)) has significantly stronger effect on the structural polarity than the introduction of a third element at the B site (Nb(5+) or Sn(4+) doped in PbSc0.5Ta0.5O3). The A-site substitution by cations that in contrast to Pb(2+) have isotropic outermost electron shells disturbs the system of lone-pair electrons, thus reducing the correlation length of coupled polar distortions and the strength of the electric field associated with the mean polarization of polar nanoregions. A-site doping with larger cations (Ba(2+)) augments the polar deformation of the individual BO6 octahedra due to local elastic fields. As a result, such A-site doping intensifies the initial structural polarity at high temperatures and prevails the enlargement of the polar fraction at low temperatures. A-site doping with smaller cations (Sr(2+), La(3+)), regardless if they are isovalent or aliovalent to Pb(2+), increases the correlation length of antiferrodistortive order (BO6 tilts), which in turn assists the development of double-perovskite structure with coherent local polar distortions. A-site doping with aliovalent cations (Bi(3+)) having the same outermost electron shell and ionic radius as the host A-site Pb(2+) cations leads to stronger coupling along the -B-O-B- bond linkages due to enhanced random local electric fields. PMID- 27661389 TI - ToF-SIMS and Laser-SNMS Imaging of Heterogeneous Topographically Complex Polymer Systems. AB - Heterogeneous polymer coatings, such as those used in organic electronics and medical devices, are of increasing industrial importance. In order to advance the development of these types of systems, analytical techniques are required which are able to determine the elemental and molecular spatial distributions, on a nanometer scale, with very high detection efficiency and sensitivity. The goal of this study was to investigate the suitability of laser postionization secondary neutral mass spectrometry (Laser-SNMS) with a 157 nm postionization laser beam to image structured polymer mixtures and compare the results with time-of-flight secondary ion mass spectrometry (ToF-SIMS) measurements using Bi3+ primary ions. The results showed that Laser-SNMS is better suited than ToF-SIMS for unambiguous detection and submicrometer imaging of the wide range of polymers investigated. The data also showed that Laser-SNMS has the advantage of being much more sensitive (in general higher by more than an order of magnitude and peaking at up to 3 orders of magnitude) than ToF-SIMS while also showing superior performance on topographically complex structured insulating surfaces, due to significantly reduced field effects and a higher dynamic range as compared to ToF-SIMS. It is concluded that Laser-SNMS is a powerful complementary technique to ToF-SIMS for the analysis of heterogeneous polymers and other complex structured organic mixtures, providing submicrometer resolution and high sensitivity. PMID- 27661390 TI - Low rates of symptomatic venous thromboembolism in patients with gastrointestinal cancer: an Iranian study. AB - : Venous thromboembolism (VTE), which mostly includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is associated with considerable morbidity and mortality in patients with cancer. As little is known about VTE associated with gastrointestinal cancers among the populations in the Middle East. This study aimed to determine the relative frequency of symptomatic VTE in patients with gastrointestinal malignancies in Iran. The charts of patients with gastrointestinal cancers in our institute from April 2010 to March 2015 were investigated for symptomatic VTE in a retrospective study. In this study, all of the patients received chemotherapy. The data included the site of cancer, time of therapies initiation, patient's characteristics, type of VTE, the time of developing symptomatic VTE of patients with gastrointestinal cancer and the stage which VTE occurred. All of DVTs and pulmonary embolism were confirmed by Doppler ultrasonography and computed tomography angiography. A total of 614 consecutive patients with gastrointestinal cancer were included in study. In total, 22 patients (3.6%) were found to have experienced symptomatic VTE (confidence interval 95%: 2.1-5.1%) which included: 19 patients who suffered from DVT and three of them detected pulmonary embolism, and other types of VTE were not reported. Out of 22 patients with VTE, 17 of them have been occurred after chemotherapy (77%) within 6.17 +/- 5.17 (range, 1-19) month after starting chemotherapy. The distribution of frequency of stage in which the VTE occurred, was more in stage III and IV. The rate of symptomatic VTE in patients with gastrointestinal cancer in Iran is relatively lower than other studies done in the west. Therefore, it seems the rate of VTE differs in different ethnic groups. PMID- 27661391 TI - PROMIS for Orthopaedic Outcomes Measurement. AB - Patient-reported outcome measures have become important tools for assessing health status in a variety of patient populations. Many historically or commonly used patient-reported outcome measures in orthopaedics are narrow in scope and are limited by the burden associated with their administration, making them useful only for specific populations. The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to overcome these limitations. The system was developed using item response theory, which allows for reliable and efficient estimation of underlying health traits using targeted item banks to assess physical function in the upper and lower extremities. PROMIS has been validated in patient populations with orthopaedic disorders of the foot and ankle, upper extremity, and spine and has demonstrated a marked improvement in measurement characteristics and reduced patient and administrative burden. PROMIS Physical Function measures are useful for assessing orthopaedic outcomes and are superior to legacy measures in several key populations. PMID- 27661392 TI - Resident Physician Duty-hour Requirements: What Does the Public Think? AB - INTRODUCTION: To date, no study has reported on the public's opinion of orthopaedic resident duty-hour requirements (DHR). METHODS: A survey was administered to people in orthopaedic waiting rooms and at three senior centers. Responses were analyzed to evaluate seven domains: knowledge of duty hours; opinions about duty hours; attitudes regarding shift work; patient safety concerns; and the effects of DHRs on continuity of care, on resident training, and on resident professionalism. RESULTS: Respondents felt that fatigue was unsafe and duty hours were beneficial in preventing resident physician fatigue. They supported the idea of residents working in shifts but did not support shifts for attending physicians. However, respondents wanted the same resident to provide continuity of care, even if that violated DHRs. They were supportive of increasing the length of residency to complete training. DHRs were not believed to affect professionalism. Half of the respondents believed that patient opinion should influence policy on this topic. DISCUSSION: Orthopaedic patients and those likely to require orthopaedic care have inconsistent opinions regarding DHRs, making it potentially difficult to incorporate their preferences into policy. PMID- 27661395 TI - New Insights into the Dynamics of Zwitterionic Micelles and Their Hydration Waters by Gigahertz-to-Terahertz Dielectric Spectroscopy. AB - Gigahertz-to-terahertz spectroscopy of macromolecules in aqueous environments provides an important approach for identifying their global and transient molecular structures, as well as directly assessing hydrogen-bonding. We report dielectric properties of zwitterionic dodecylphosphocholine (DPC) micelles in aqueous solutions over a wide frequency range, from 50 MHz to 1.12 THz. The dielectric relaxation spectra reveal different polarization mechanisms at the molecular level, reflecting the complexity of DPC micelle-water interactions. We have made a deconvolution of the spectra into different components and combined them with the effective-medium approximation to separate delicate processes of micelles in water. Our measurements demonstrate reorientational motion of the DPC surfactant head groups within the micelles, and two levels of hydration water shells, including tightly and loosely bound hydration water layers. From the dielectric strength of bulk water in DPC solutions, we found that the number of waters in hydration shells is approximately constant at 950 +/- 45 water molecules per micelle in DPC concentrations up to 400 mM, and it decreases after that. At terahertz frequencies, employing the effective-medium approximation, we estimate that each DPC micelle is surrounded by a tightly bound layer of 310 +/- 45 water molecules that behave as if they are an integral part of the micelle. Combined with molecular dynamics simulations, we determine that tightly bound waters are directly hydrogen-bonded to oxygens of DPC, while loosely bound waters reside within 4 A of micellar atoms. The dielectric response of DPC micelles at terahertz frequencies yields, for the first time, experimental information regarding the largest scale, lowest frequency collective motions in micelles. DPC micelles are a relatively simple biologically relevant system, and this work paves the way for more insight into future studies of hydration and dynamics of biomolecular systems with gigahertz-to-terahertz spectroscopy. PMID- 27661396 TI - News and Views-November 2016. PMID- 27661394 TI - Association Between Executive Function and Problematic Adolescent Driving. AB - OBJECTIVE: Motor vehicle collisions (MVCs) are one of the leading causes of injury and death for adolescents. Driving is a complex activity that is highly reliant on executive function (EF) to safely navigate through the environment. Little research has examined the efficacy of using self-reported EF measures for assessing adolescent driving risk. This study examined the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire and performance-based EF tasks as potential predictors of problematic driving outcomes in adolescents. METHODS: Forty-six adolescent drivers completed the (1) BRIEF, (2) Trail Making Test, (3) Backwards Digit Span, and (4) self-report on 3 problematic driving outcomes: the number of times of having been pulled over by a police officer, the number of tickets issued, and the number of MVCs. RESULTS: Greater self-reported difficulty with planning and organization was associated with greater odds of having a MVC, whereas inhibition difficulties were associated with greater odds of receiving a ticket. Greater self-reported difficulty across multiple BRIEF subscales was associated with greater odds of being pulled over. CONCLUSION: Overall findings indicated that the BRIEF, an ecological measure of EF, showed significant association with self-reported problematic driving outcomes in adolescents. No relationship was found between performance-based EF measures and self-reported driving outcomes. The BRIEF could offer unique and quick insight into problematic driving behavior and potentially be an indicator of driving risk in adolescent drivers during clinical evaluations. PMID- 27661393 TI - Investigation of the Biological Impact of Charge Distribution on a NTR1-Targeted Peptide. AB - The neurotensin receptor 1 (NTR1) has been shown to be a promising target, due to its increased level of expression relative to normal tissue, for pancreatic and colon cancers. This has prompted the development of a variety of NTR1-targeted radiopharmaceuticals, based on the neurotensin (NT) peptide, for diagnostic and radiotherapeutic applications. A major obstacle for the clinical translation of NTR1-targeted radiotherapeutics would likely be nephrotoxicity due to the high levels of kidney retention. It is well-known that for many peptide-based agents, renal uptake is influenced by the overall molecular charge. Herein, we investigated the effect of charge distribution on receptor binding and kidney retention. Using the [(N-alpha-Me)Arg8,Dmt11,Tle12]NT(6-13) targeting vector, three peptides (177Lu-K2, 177Lu-K4, and 177Lu-K6), with the Lys moved closer (K6) or further away (K2) from the pharmacophore, were synthesized. In vitro competitive binding, internalization and efflux, and confocal microscopy studies were conducted using the NTR1-positive HT-29, human colon cancer cell line. The 177/natLu-K6 demonstrated the highest binding affinity (21.8 +/- 1.2 nM) and the highest level of internalization (4.06% +/- 0.20% of the total added amount). In vivo biodistribution, autoradiography, and metabolic studies of 177Lu radiolabeled K2, K4, and K6 were examined using CF-1 mice. 177Lu-K4 and 177Lu-K6 gave the highest levels of in vivo uptake in NTR1-positive tissues, whereas 177Lu K2 yielded nearly 2-fold higher renal uptake relative to the other radioconjugates. In conclusion, the position of the Lys (positively charged amino acid) influences the receptor binding, internalization, in vivo NTR1-targeting efficacy, and kidney retention profile of the radioconjugates. In addition, we have found that hydrophobicity likely play a role in the unique biodistribution profiles of these agents. PMID- 27661397 TI - Synthesis and Characterization of an Iridium Triphyrin Complex. AB - A sandwich complex of iridium(III) benzotriphyrin (2) has been synthesized from free-base benzotriphyrin (1) and [IrCl(cod)]2 (COD = 1,5-cyclooctadiene). The COD ring was transformed from 1,5-COD to an eta1,eta3-C8H12 unit as a pi-allyl ligand associated with the valence change of iridium from IrI to IrIII, as revealed by X ray diffraction analysis. The Soret-like band of 2 was blue-shifted and broadened compared with that of 1, indicating strong electronic interactions between triphyrin and the iridium ion. Compound 2 also showed very broad absorption in the range of 500-800 nm, which can be assigned to a mixture of Q and metal-to ligand charge-transfer bands. PMID- 27661398 TI - Population Pharmacokinetics of Everolimus in Relation to Clinical Outcomes in Patients With Advanced Renal Cell Carcinoma. AB - BACKGROUND: Everolimus has been used for the treatment of unresectable or metastatic renal cell carcinoma (RCC). Here, we measured blood concentrations of everolimus to obtain the population pharmacokinetic parameters and to examine the relationship between blood concentration and clinical outcomes. METHODS: Twenty two Japanese patients were enrolled. Blood samples were collected before and 2, 4, 8, and 24 hours after drug administration on days 1 and 8 of everolimus therapy (5 or 10 mg) from inpatients; occasional samples were collected from outpatients. Blood concentrations of everolimus were measured by high-performance liquid chromatography with tandem mass spectrometry. Population pharmacokinetic analysis was conducted using the NONMEM software. RESULTS: Everolimus pharmacokinetics was best described by a 2-compartment model with population mean estimates of apparent oral clearance of 10.0 L/h and an interindividual variability of 42.4%. There was no relationship between overall best responses and the predicted trough concentrations at day 8. The predicted trough concentration in patients who terminated everolimus treatment owing to adverse drug reactions (ADRs) was significantly higher than in patients who stopped the treatment owing to disease progression or other reasons (27.6 +/- 3.1 versus 15.7 +/- 2.3 ng/mL; mean +/- SEM). Patients who terminated the treatment owing to ADRs had significantly shorter time-to-treatment failure than other patients (112 versus 187 days, median). CONCLUSIONS: This study reports the first population pharmacokinetic parameters of everolimus in patients with RCC. Individual dose adjustment based on everolimus blood concentrations helps to avoid early drug cessation due to ADRs. PMID- 27661399 TI - Relative Bioavailabilities of Lisdexamfetamine Dimesylate and D-Amphetamine in Healthy Adults in an Open-Label, Randomized, Crossover Study After Mixing Lisdexamfetamine Dimesylate With Food or Drink. AB - BACKGROUND: This open-label, crossover study examined lisdexamfetamine dimesylate (LDX) and D-amphetamine pharmacokinetics in healthy adults after administration of an intact LDX capsule or after the capsule was emptied into orange juice or yogurt and the contents consumed. METHODS: Healthy adult volunteers (N = 30) were administered a 70-mg LDX capsule or the contents of a 70-mg capsule mixed with yogurt or orange juice using a 3-way crossover design. Blood samples were collected serially for up to 96 hours after dose. Pharmacokinetic endpoints included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from zero to infinity (AUC0-infinity) or to last assessment (AUClast). Relative LDX and D-amphetamine bioavailabilities from the contents of a 70-mg LDX capsule mixed with orange juice or yogurt were compared with those from the intact LDX capsule using bioequivalence-testing procedures. RESULTS: Geometric least squares mean ratios (90% confidence intervals [CIs]) for D-amphetamine (active moiety) were within the prespecified bioequivalence range (0.80-1.25) when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.971 (0.945, 0.998); AUC0-infinity: 0.986 (0.955, 1.019); AUClast: 0.970 (0.937, 1.004)] or yogurt [Cmax: 0.970 (0.944, 0.997); AUC0-infinity: 0.945 (0.915, 0.976); AUClast: 0.944 (0.912, 0.977)]. Geometric least squares mean ratios (90% CIs) for LDX (inactive prodrug) were below the accepted range when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.641 (0.582, 0.707); AUC0-infinity: 0.716 (0.647, 0.792); AUClast: 0.708 (0.655, 0.766)]; the lower 90% CI for Cmax [0.828 (0.752, 0.912)] was below the accepted range when the contents of a 70-mg LDX capsule were mixed with yogurt. CONCLUSIONS: Relative bioavailability of D-amphetamine (the active moiety) did not differ across administrations, which suggests that emptying an LDX capsule into orange juice or yogurt and consuming it is an alternative to intact capsules. PMID- 27661400 TI - Analytical Validation and Cross-Validation of an NFAT-Regulated Gene Expression Assay for Pharmacodynamic Monitoring of Therapy With Calcineurin Inhibitors. AB - BACKGROUND: Analysis of residual gene expression of the nuclear factor of activated T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to monitor therapy with calcineurin inhibitors. The availability of commercial primer sets (Search-LC) and the well-established assay protocol makes this biomarker a promising candidate to be used clinically in different laboratories. However, implementation of the method in routine practice requires analytical robustness and comparable results across laboratories. Therefore, a protocol originally established at the Institute of Immunology, Heidelberg was verified at the Institute of Laboratory Medicine, Klinikum Stuttgart, and a comparison study was conducted between the 2 laboratories. METHODS: For the analytical verification, whole blood samples of healthy individuals were incubated with tacrolimus in vitro. Linearity, imprecision, and limit of quantification, as well as sample stability, were investigated. For interlaboratory comparison, samples of patients under cyclosporine A therapy were analyzed in Heidelberg and then reanalyzed in Stuttgart within 24 hours. RESULTS: Tacrolimus (6.25-50 mcg/L) decreased the expression of NFAT-regulated genes in vitro dose dependently (15%-89%). Within- and between-assay coefficient of variations (n = 6 each) were <17%. The limit of quantification was <200 cDNA copies for each of the interleukin-2, interferon-gamma, and granulocyte macrophage colony-stimulating factor genes. Samples were stable for 24 hours. Interlaboratory comparison using patient samples correlated well (r = 0.951) but showed an inconsistent bias depending on the magnitude of residual gene expression. CONCLUSIONS: The assay can be set up with a satisfactory analytical performance in a routine molecular biological laboratory and shows comparable results between laboratories. The reproducibility of the NFAT-regulated gene expression assay across laboratories can facilitate the implementation of this assay for pharmacodynamic routine monitoring of calcineurin inhibitors in different centers. PMID- 27661401 TI - Gentamicin Pharmacokinetics and Monitoring in Pediatric Febrile Neutropenic Patients. AB - BACKGROUND: The pharmacokinetics of gentamicin in pediatric febrile neutropenia patients is described and the adequacy of initial dosing of once daily gentamicin assessed at Queensland's largest Children's Hospital. METHODS: Data were retrospectively collected from all pediatrics with febrile neutropenia admitted over a two-year period who had at least two gentamicin concentration-time measurements (a paired set within one dosing interval). Gentamicin clearance (CL), volume of distribution (Vd), area under the concentration-time curve from 0 to 24 hours post-dose (AUC0-24), and maximum concentration (Cmax) values were estimated using log-linear regression using each paired set. The percentage of paired sets associated with gentamicin exposure within pre-defined hospital targets was calculated and exposure was examined in relation to bacterial culture status. RESULTS: Data were collected from 69 patients (median [IQR] age 3.7 years [2.2, 8.9]) and comprised 121 paired concentration sets characterizing 80 separate admissions. Median [IQR] gentamicin CL and Vd were 8.1 L/h/70 kg [5.8, 12.4] and 21.8 L/70 kg [16.9, 29.5], respectively. Pre-defined hospital exposure targets were achieved for both AUC0-24 and Cmax for 10% of paired sets; one or the other of these targets were met for 36% of paired sets and neither target was achieved for 54% of paired sets. Achievement of targets improved with repeated monitoring during the same admission. Median AUC0-24 achieved was significantly higher in patients with a confirmed Gram-negative infection compared to those without 71 [50, 91] mg.h/L versus 55 [40.8, 67.5] mg.h/L, respectively (p= 0.003)). Over the study period, a median gentamicin dose of 10.8 and 6.4 mg/kg was estimated to be necessary to achieve an AUC target of 80 mg.h/L in children <=10 years and >10 years of age. CONCLUSIONS: Based on a log-linear method of analysis, current dosing appears to be consistently producing gentamicin exposure below pre-defined pharmacokinetic targets, suggesting that an increase in the recommended starting dose of gentamicin may be required. PMID- 27661402 TI - Placental implantation abnormalities: a modern approach. AB - PURPOSE OF REVIEW: Placental implantation abnormalities (PIAs) comprise a large group of disorders associated with significant maternal, fetal, and neonatal morbidity. RECENT FINDINGS: Risk factors include prior uterine surgery/myometrial scarring and the presence of placenta previa with or without prior cesarean delivery. Newly identified risk factors include previous prelabor cesarean delivery and previous postpartum hemorrhage. PIAs contribute substantially to preterm birth with prematurity rates ranging from 38 to 82%. Diagnosis is typically made by ultrasound in the second or third trimester; transvaginal ultrasound and color Doppler are useful in evaluating for placental invasion, placental edge thickness, presence of fetal vessels, and cervical length. Suggestive MRI features include increased vascularity, dark T2 bands, uterine bulging, thin or indistinct myometrium, and loss of dark T2 interface. An important first-trimester finding is the implantation of the gestational sac into prior hysterotomy scar (cesarean scar pregnancy). Recommendations for delivery are universally preterm and based on expert opinion. Proposed management strategies are outlined depending on cervical length, distance between internal cervical os and placenta, and placental edge thickness. SUMMARY: There has been a recent shift in focus to individualizing management in order to improve delivery timing and in some cases even decrease risks associated with prematurity. There is a need for larger prospective studies or randomized trials to show that individualizing care can improve outcomes. PMID- 27661403 TI - Driving under the influence of distraction: Examining dissociations between risk perception and engagement in distracted driving. AB - Driving while distracted is a critical and unwavering problem in the United States leading to numerous injuries and fatalities each year. While increasing legislation and developing technological interventions strive to ensure we only focus on driving, individuals still drive distracted. We surveyed college-aged adults to examine the factors that influence both their risk perception of driving while distracted and how often they engage in distracting activities and situations while driving. We found a disassociation between individuals' perception of driving distraction risk and their engagement with the distraction. Exposure, perceived knowledge of risks, fairness beliefs, and ratings of perceived visual and cognitive demands was associated with risk perception. Conversely, risk-seeking traits, how voluntary the task was perceived, and previous exposure to a distraction influenced engagement. Overall, we recommend additional research focusing on factors that predict engagement in driver distraction rather than perceived risk alone. PMID- 27661404 TI - PCM1 Depletion Inhibits Glioblastoma Cell Ciliogenesis and Increases Cell Death and Sensitivity to Temozolomide. AB - A better understanding of the molecules implicated in the growth and survival of glioblastoma (GBM) cells and their response to temozolomide (TMZ), the standard of-care chemotherapeutic agent, is necessary for the development of new therapies that would improve the outcome of current GBM treatments. In this study, we characterize the role of pericentriolar material 1 (PCM1), a component of centriolar satellites surrounding centrosomes, in GBM cell proliferation and sensitivity to genotoxic agents such as TMZ. We show that PCM1 is expressed around centrioles and ciliary basal bodies in patient GBM biopsies and derived cell lines and that its localization is dynamic throughout the cell cycle. To test whether PCM1 mediates GBM cell proliferation and/or response to TMZ, we used CRISPR/Cas9 genome editing to generate primary GBM cell lines depleted of PCM1. These PCM1-depleted cells displayed reduced AZI1 satellite protein localization and significantly decreased proliferation, which was attributable to increased apoptotic cell death. Furthermore, PCM1-depleted lines were more sensitive to TMZ toxicity than control lines. The increase in TMZ sensitivity may be partly due to the reduced ability of PCM1-depleted cells to form primary cilia, as depletion of KIF3A also ablated GBM cells' ciliogenesis and increased their sensitivity to TMZ while preserving PCM1 localization. In addition, the co-depletion of KIF3A and PCM1 did not have any additive effect on TMZ sensitivity. Together, our data suggest that PCM1 plays multiple roles in GBM pathogenesis and that associated pathways could be targeted to augment current or future anti-GBM therapies. PMID- 27661405 TI - Diffusion-Weighted Imaging Using a Readout-Segmented, Multishot EPI Sequence at 3 T Distinguishes between Morphologically Differentiated and Undifferentiated Subtypes of Thyroid Carcinoma-A Preliminary Study. AB - BACKGROUND: Thyroid carcinomas represent the most frequent endocrine malignancies. Recent studies were able to distinguish malignant from benign nodules of the thyroid gland with diffusion-weighted imaging (DWI). Although this differentiation is undoubtedly helpful, presurgical discrimination between well differentiated and undifferentiated carcinomas would be crucial to define the optimal treatment algorithm. Therefore, the aim of this study was to investigate if readout-segmented multishot echo planar DWI is able to differentiate between differentiated and undifferentiated subtypes of thyroid carcinomas. PATIENTS AND METHODS: Fourteen patients with different types of thyroid carcinomas who received preoperative DWI were included in our study. In all lesions, apparent diffusion coefficient (ADC)min, ADCmean, ADCmax, and D were estimated on the basis of region of interest measurements after coregistration with T1-weighted, postcontrast images. All tumors were resected and analyzed histopathologically. Ki-67 index, p53 synthesis, cellularity, and total and average nucleic areas were estimated using ImageJ version 1.48. RESULTS: Analysis of variance revealed a statistically significant difference in ADCmean values between differentiated and undifferentiated thyroid carcinomas (P=.022). Spearman Rho calculation identified significant correlations between ADCmax and cell count (r=0.541, P=.046) as well as between ADCmax and total nuclei area (r=0.605, P=.022). CONCLUSION: DWI can distinguish between differentiated and undifferentiated thyroid carcinomas. PMID- 27661406 TI - Oral Health Behaviors and Perceptions Among College Students. AB - Oral health is a simple and important part of college students' lives but might often be overlooked or undermined because of increased stress levels and unhealthy habits associated with the college setting. Despite the challenges, college days may be one of the best times to establish lifelong healthy habits, including oral health routines. The purpose of this study was to determine the current oral care behaviors and perceptions of students at a midwestern college. This study was nonexperimental in nature with a quantitative method and a cross sectional design, which included 126 participants. The survey instrument included 2 Likert-type scales. The oral health-related quality-of-life model was used as the theoretical framework to guide the study. PMID- 27661407 TI - A Qualitative Study of the Change-of-Shift Report at the Patients' Bedside. AB - Concerns about patient bedside change-of-shift reporting at a community hospital in northern Indiana stimulated the development of this qualitative phenomenological study. A review of the literature revealed a research deficit in acute care nurses' perceptions of bedside reporting in relation to compliance. The research question addressed in this study was, "What are acute care nurses' perceptions of the change-of-shift report at the patients' bedside?" Personal interviews were conducted on 7 medical, surgical, and intensive care unit nurse participants at a community hospital in northern Indiana. Five themes were identified from the collected data, which included the time factor, continuity of care, visualization, and challenges in the communication of discreet information. PMID- 27661408 TI - 1,4-Addition Ugi Reaction Using Cyclic alpha,beta-Unsaturated Ketone as Substrate. AB - A four-component, 1,4-addition Ugi reaction using cyclic alpha,beta-unsaturated ketones, carboxylic acids, amines, and isocyanides was developed for the first time. By combining this reaction with Michael addition, nucleophilic substitution, and C-N bond formation reactions, bicyclic and tricyclic scaffolds with pyridinone and quinolinone moieties, two basic units among a variety of natural products and pharmaceuticals, were constructed. PMID- 27661409 TI - Diagnosis and causal explanation in psychiatry. AB - In clinical medicine, a diagnosis can offer an explanation of a patient's symptoms by specifying the pathology that is causing them. Diagnoses in psychiatry are also sometimes presented in clinical texts as if they pick out pathological processes that cause sets of symptoms. However, current evidence suggests the possibility that many diagnostic categories in psychiatry are highly causally heterogeneous. For example, major depressive disorder may not be associated with a single type of underlying pathological process, but with a range of different causal pathways, each involving complex interactions of various biological, psychological, and social factors. This paper explores the implications of causal heterogeneity for whether psychiatric diagnoses can be said to serve causal explanatory roles in clinical practice. I argue that while they may fall short of picking out a specific cause of the patient's symptoms, they can nonetheless supply different sorts of clinically relevant causal information. In particular, I suggest that some psychiatric diagnoses provide negative information that rules out certain causes, some provide approximate or disjunctive information about the range of possible causal processes, and some provide causal information about the relations between the symptoms themselves. PMID- 27661410 TI - The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline. AB - Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious protective dichotomy of APOE variants on attentional control in mid-adulthood. Sixty-six volunteers, aged 45-55 years, completed 3 tasks that provided complementary measures of attentional control: prospective memory, sustained attention, and inhibition. Performance was compared between e2 carriers, e4 carriers, and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared with the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes. PMID- 27661411 TI - Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome. AB - BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiomyopathy associated with intense physical or emotional stress. The precise mechanisms of the disease remain unclear. The aim of this study was to study alterations in endothelial function, vascular compliance and structure and muscle sympathetic activity in the stable phase of the disease. METHODS: In this prospective observational study, patients with TTS and controls matched for age, sex, cardiovascular risk factors and medications were recruited. Flow-mediated vasodilatation (FMD) as a measure of endothelial dysfunction was the primary endpoint. Secondary endpoints included measurements of arterial stiffness, carotid atherosclerosis, quality of life and laboratory parameters. In a subset of patients, muscle sympathetic activity was measured before and after stress tests. RESULTS: The study included 22 TTS patients and 21 matched controls. A significant increase in endothelial dysfunction was seen in TTS compared to controls (FMD 3.4+/-2.4% vs. 4.8+/-1.9%, p=0.016). No significant differences in arterial stiffness, intima-media thickness, quality of life and laboratory markers including endothelin-1 were noted. TTS patients showed a reduced carotid total plaque area compared to controls (TPA 17.3+/-15.1 vs 24.7+/-12.8mm2, p=0.02). A trend of increased muscle sympathetic activity at rest was observed in TTS patients vs. controls (53.5+/ 28.4 vs. 29.4+/-16.5 bursts/100 heart beats, p=0.09) with no significant differences in muscle sympathetic activity in response to stress. CONCLUSIONS: Our findings underscore the importance of endothelial dysfunction in patients with TTS which may be involved in the pathophysiology of this syndrome. CLINICALTRIALS. GOV IDENTIFIER: NCT01249599. PMID- 27661412 TI - Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure. AB - BACKGROUND: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF) specific circulating miRNAs and well-known heart failure biomarkers. METHODS: Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis. RESULTS: No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-0.68, p-value=0.002), miR-223-3p to growth differentiation factor 15 (R=-0.69, p-value=0.0015), miR-652-3p to soluble ST-2 (R=-0.77, p value<0.001), miR-199a-3p to procalcitonin (R=-0.72, p-value<0.001) and galectin 3 (R=-0.73, p-value<0.001) and miR-18a-5p to procalcitonin (R=-0.68, p value=0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA biomarker correlations. CONCLUSIONS: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers. PMID- 27661413 TI - Late recurrence of left ventricular dysfunction after aortic valve replacement for severe chronic aortic regurgitation. AB - BACKGROUND: Aortic valve replacement (AVR) for chronic aortic regurgitation (AR) with a decreased ejection fraction (EF) leads to improvement in left ventricular (LV) function, but there are no reports on late recurrence of LV dysfunction over long-term after AVR. This study aimed to identify frequency and predictors of late recurrent LV dysfunction after AVR. METHODS: We retrospectively investigated 58 consecutive patients undergoing AVR for severe chronic AR and with follow-up echocardiography for >5years after AVR. Late recurrence of LV dysfunction was defined as an EF of <50% late after AVR and a 10% reduction in the EF compared with that observed at 1year after AVR. RESULTS: The mean follow-up period was 10.3+/-5.2years. The preoperative EF was <50% in 21 (36%) patients, but it was normalized at 1year after AVR in all patients except for one. However, late recurrence of LV dysfunction developed in 7 (12%) of the 58 patients. These patients showed significantly higher LV end-diastolic and end-systolic diameters before and at 1year after AVR, a lower EF and relative wall thickness before AVR, a higher LV mass index at 1year after AVR, and a higher incidence of preoperative and postoperative atrial fibrillation than those without late recurrence. CONCLUSIONS: Late recurrent LV dysfunction may occur after AVR for severe chronic AR despite EF being once normalized. Early surgery proceeding remarkable LV enlargement and maintaining sinus rhythm are important for LV function over the long-term after AVR. PMID- 27661414 TI - Circulating sex hormones, alcohol consumption and echocardiographic parameters of cardiac function in men with heart failure. PMID- 27661415 TI - Ivabradine reduced ventricular rate in patients with non-paroxysmal atrial fibrillation. AB - BACKGROUND: It has been shown that If channels can be found in AV node, apart from the sinus node. Previous animal studies showed that If inhibitor resulted in the rate-dependent reduction in AV node conduction during atrial fibrillation (AF). Therefore, we aimed to examine the effect of ivabradine on ventricular rate in patients with non-paroxysmal AF. METHOD: This study was a prospective randomized, double blind, placebo-controlled study. Ivabradine, 5mg twice a day (n=21), or placebo (n=11) was administered for 1month to adult patients with non paroxysmal AF, in addition to standard therapy. The primary end point was the change in mean ventricular rate between baseline and 1month, as assessed by 24 hour Holter. RESULTS: The baseline characteristics did not differ between ivabradine and placebo groups (mean age was 59.7+/-13.3years, male 62.5%). Mean 24-hour ventricular rate at baseline was comparable between 2 groups. We found that ivabradine significantly decreased mean ventricular rate from 86.0+/ 10.9beats/min to 79.2+/-9.6beats/min (p<0.001). In contrast, no significant change in ventricular rate was observed in placebo group (84.3+/-11.2 vs. 82.9+/ 9.9beats/min, p=0.469). The effect of ivabradine on rate reduction was significantly greater than placebo (6.9+/-6.3 vs. 1.4+/-6.0beats/min, p=0.024). No drug-related adverse effects were observed in both groups. CONCLUSION: We demonstrated that ivabradine significantly decreased ventricular rate during AF compared to placebo. Therefore, ivabradine can be a potential treatment to improve ventricular control in patients with non-paroxysmal AF. Due to the small sample size, larger studies are needed to confirm this effect of ivabradine. PMID- 27661416 TI - Psychological pathway to suicidal ideation among men who have sex with men in Shanghai, China: A structural equation model. AB - We aimed to explore the relationships and develop an inter-theoretical model among psychological variables in the progression to suicidal ideation among men who have sex with men (MSM). A cross-sectional study was conducted among 547 MSM in four districts in Shanghai from March to May in 2014. Socio-demographic, psychological, and behavioral information of the participants was collected. A structural equation model (SEM)-Path Analysis was constructed to interpret the intricate relationships among various psychological variables. Suicidal ideation among MSM during the past year was 10.6%. The developed model agreed well with existing suicide models and had a good fit to the data (chi2/df = 2.497, comparative fit index = 0.983, root mean squared error of approximation = 0.052). Suicidal ideation was predicted by perceived defeat and entrapment (beta = 0.21, p < 0.001), which was in turn predicted by temperament (beta = 0.60, p < 0.001) and perceived social support (beta = 0.34, p < 0.001). Perceived social support fully mediated the relationships among mood states, perceived social status, and perceived defeat and entrapment. MSM with certain types of temperament might be predisposed to a higher perception of defeat and entrapment. Perceived social support can effectively alleviate the negative appraisals and emotions and lower the risk for suicidal ideation among MSM. PMID- 27661417 TI - Sleep and circadian alterations in people at risk for bipolar disorder: A systematic review. AB - BACKGROUND: Sleep and circadian abnormalities have been mostly demonstrated in bipolar patients. However, it is not clear whether these alterations are present in population at high risk for bipolar disorder (BD), indicating a possible risk factor for this condition. OBJECTIVE: This systematic review aims to define current evidence about sleep and rhythm alterations in people at risk for BD and to evaluate sleep and circadian disorders as risk factor for BD. METHODS: The systematic review included all articles about the topic until February 2016. Two researchers performed an electronic search of PubMed and Cochrane Library. Keywords used were 'sleep' or 'rhythm' or 'circadian' AND 'bipolar disorder' or 'mania' or 'bipolar depression' AND 'high-risk' or 'risk'. RESULTS: Thirty articles were analyzed (7451 participants at risk for BD). Sleep disturbances are frequent in studies using both subjective measures and actigraphy. High-risk individuals reported irregularity of sleep/wake times, poor sleep and circadian rhythm disruption. Poor sleep quality, nighttime awakenings, and inadequate sleep are possible predictive factors for BD. A unique study suggested that irregular rhythms increase risk of conversion. People at risk for BD showed high cortisol levels in different times of day. Studies about anatomopathology, melatonin levels, inflammatory cytokines and oxidative stress were not identified. The most important limitations were differences in sleep and rhythm measures, heterogeneity of study designs, and lack of consistency in the definition of population at risk. CONCLUSION: Sleep and circadian disturbances are common in people at risk for BD. However, the pathophysiology of these alterations and the impact on BD onset are still unclear. PMID- 27661419 TI - Introduction. PMID- 27661420 TI - Lower Extremity Limb Salvage: Lessons Learned From 14 Years at War. AB - American survivability during the current conflicts in Iraq and Afghanistan continues to improve, though the rate of extremity injury remains quite high. The decision to proceed with amputation versus limb salvage remains controversial. Exposure to combat wound with severe high-energy lower extremity trauma during the previous 14 years at war has incited important advances in limb salvage technique and rehabilitation. PMID- 27661421 TI - What Is New in Trauma-Related Amputations. AB - Traumatic and trauma-related amputations represent unfortunate sequelae of severe injury, but should not be viewed as a treatment failure and may represent the best reconstructive option for some patients. Lessons from recent military conflicts have guided the evolution of modern surgical techniques and rehabilitation management of this challenging patient population, and treatment at a specialty center may improve patient outcomes. Despite appropriate management, however, surgical complications remain common and revision surgery is often necessary. Bridge synostosis procedures remain controversial, and clinical equipoise remains regarding their functional benefits. Based on European experience over the last 3 decades, osseointegration has evolved into a viable clinical alternative for patients unable to achieve acceptable function using conventional sockets, and several devices are being developed or tested in the United States. Targeted muscle reinnervation and advanced pattern recognition may dramatically improve the functional potential of many upper extremity amputees, and the procedure may also relieve neuroma-related pain. Furthermore, exciting new research may eventually facilitate haptic feedback and restore useful sensation for amputees. Natural disasters and global terrorism events, in addition to conventional trauma resulting in limb loss, make a working knowledge of current amputation surgical techniques essential to the practicing orthopaedic trauma surgeon. PMID- 27661422 TI - Resuscitation and Treatment of Shock. AB - Hemorrhage continues to be the most common cause of death among service members wounded in combat. Injuries that were previously nonsurvivable in previous wars are now routinely seen by combat surgeons in forward surgical units, the result of improvements in body armor, the universal use of field tourniquets to control extremity hemorrhage at the point of injury, and rapid air evacuation strategies. Combat orthopaedic surgeons remain a vital aspect of the forward surgical unit, tasked with assisting general surgical colleagues in the resuscitation of patients in hemorrhagic shock while also addressing traumatic amputations, open and closed long bone fractures, and mechanically unstable pelvic trauma. Future military and civilian trauma research endeavors will seek to identify how the advances made in the past 15 years will translate toward the emerging battlefield of the future, one where forward surgical units must be lighter, smaller, and more mobile to address the changing scope of military combat operations. PMID- 27661418 TI - Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims. AB - BACKGROUND: Major depressive disorder (MDD) is a serious psychiatric illness, associated with an increasing rate of suicide. The pathogenesis of depression may be associated with the disruption of zinc (Zn) homeostasis. In the brain, several proteins that regulate Zn homeostasis are present, including Zn transporters (ZnTs) which remove Zn from the cytosol. The present study was designed to investigate whether depression and suicide are associated with alterations in the expression of the ZnTs protein. METHODS: Protein levels of ZnT1, ZnT3, ZnT4, ZnT5 and ZnT6 were measured in postmortem brain tissue from two different cohorts. Cohort A contained 10 subjects diagnosed with MDD (7 were suicide victims) and 10 psychiatrically-normal control subjects and cohort B contained 11 non-diagnosed suicide victims and 8 sudden-death control subjects. Moreover, in cohort A we measured protein level of NMDA (GluN2A subunit), AMPA (GluA1 subunit) and 5-HT1A receptors and PSD-95. Proteins were measured in the prefrontal cortex (PFC) using Western blotting. In addition, Zn concentration was measured using a voltammetric method. RESULTS: There was a significant increase in protein levels of ZnT1, ZnT4, ZnT5 in the PFC in MDD, relative to control subjects, while ZnT3 protein level was decreased in MDD. There was no significant difference in the Zn concentration in the PFC between control and MDD subjects. Similarly, in the PFC of suicide victims (non-diagnosed), an increase in protein levels of ZnT1, ZnT4, ZnT5 and ZnT6 was observed. Conversely, protein levels of ZnT3 were decreased in both suicide victims and subjects with MDD, in comparison with control subjects. There was also a significant decrease in the protein level of GluA1, GluN2A, PSD 95 and 5-HT1A in MDD. CONCLUSIONS: Our studies suggest that alterations in Zn transport proteins are associated with the pathophysiology of MDD and suicide. PMID- 27661423 TI - Infection After Orthopaedic Trauma: Prevention and Treatment. AB - Trauma to the extremities is disproportionately represented in casualties of recent conflicts, accounting for >50% of injuries sustained during operations in Iraq and Afghanistan. Infectious complications have been reported in >25% of those evacuated for trauma, and 50% of such patients were treated in the intensive care unit (ICU). Osteomyelitis has been reported in 9% (14% of intensive care unit patients), and deep-wound infection in 27% of type III open tibia fractures. Infections complicating extremity trauma are frequently caused by multidrug-resistant bacteria and have been demonstrated to lead to failure of limb salvage, unplanned operative take-backs, late amputations, and decreased likelihood of returning to duty. Invasive fungal infections of extremities have also presented a unique challenge in combat-injured patients, particularly in those with blast injuries with massive transfusion requirements and high injury severity scores. Infection prevention should begin at the time of injury and, although context-specific depending on the level of care, includes appropriate irrigation, surgical debridement, wound care and coverage, fracture fixation, and antibiotic prophylaxis, in addition to basic infection prevention measures. Clinical practice guidelines to address infection prevention after combat trauma (including extremity infection) were developed in 2007 and revised in 2011, with endorsement from the Surgical Infection Society and the Infectious Disease Society of America. Nevertheless, significant challenges remain, including austere environments of care, multiple transitions of care, and lack of coordinated efforts in prevention. Treatment of established infections is optimally multidisciplinary, particularly when deep wounds, bone, and joints are involved. Surgical debridement of overtly infected or necrotic tissue is necessary, with particularly aggressive margins if invasive fungal infection is suspected. Infected nonunion frequently requires the use of prosthetic materials for fixation, potentiating biofilm formation, and complicating medical therapy. Antibiotic therapy should be targeted at results of deep wound and bone cultures. However, this is complicated by frequent contamination of wounds, requiring differentiation between potential pathogens in terms of their virulence and decreased culture recovery in patient who have frequently received previous antibiotics. Lessons learned in infection prevention and treatment of orthopaedic trauma from combat can serve to inform the care of patients injured in natural disasters and noncombat trauma. PMID- 27661424 TI - Heterotopic Ossification: A Review of Current Understanding, Treatment, and Future. AB - Heterotopic ossification is the formation of bone at extraskeletal sites. The incidence of heterotopic ossification in military amputees from recent operations in Iraq and Afghanistan has been demonstrated to be as high as 65%. Heterotopic ossification poses problems to wound healing, rehabilitation, and prosthetic fitting. This article details the current evidence regarding its etiology, prevention, management, and research strategies. PMID- 27661425 TI - Comprehensive Rehabilitation Following Combat Extremity Trauma: Evolution and Its Impact on Outcomes. AB - Recent military combat operations have resulted in a high burden of extremity related long-term disability due to limb amputation and persistent deficits despite limb reconstruction. The US Army amputee care programs, established at focused centers with interdisciplinary care teams, have redefined the standard of how rehabilitation following limb loss is undertaken as the limb reconstruction is just one part of the entire patient's restoration of wellness and reintegration. Inspired by this approached, comprehensive rehabilitation programs designed for patients with limb reconstruction have also excelled rehabilitation following a spectrum of severe limb trauma. These programs, which include advances in orthotics and orthosis training, have improved function and military retention among the limb salvage patient population. Lessons learned from comprehensive rehabilitation efforts emphasize the value of highly skilled, interprofessional care teams and the overall wellness of the patients. Although this approach is resource intensive and not available in all health care systems, civilian trauma counterparts can learn from the example of holistic attention to the patient's recovery. PMID- 27661426 TI - Debridement and Irrigation: Evolution and Current Recommendations. AB - Debridement is an integral step in the orthopaedic management of traumatic wounds, from open soft tissue injuries and routine open fracture care to the management of extensive high-energy blast injuries. While the necessity of debridement has been well established, the level of energy and degree of contamination of blast wounds encountered in recent armed conflict has offered a challenge and a new opportunity for military surgeons to revisit the most recent literature to guide our practice with the best evidence currently available. While the core tenants of removing the nonviable tissue and preserving the viable to maintain the best functional outcome have not changed, new wound care therapies and advances in prosthetics and salvage techniques and the ability to rapidly evacuate casualties have changed the approach to care provided on the front lines. This paper seeks to review the core principles of debridement and guide treatment using evidence-based methods that can be applied to contaminated open injuries on the battlefront and disaster and intentional violence injuries abroad and at home. PMID- 27661427 TI - Intraepithelial Extramammary Paget's Disease of the Vulva: The Clinicopathological Characteristics, Management, and Outcome in a Study of 18 Female Patients. AB - OBJECTIVE: This study aimed to analyze the clinicopathologic characteristics, management, and outcome of patients with intraepithelial extramammary Paget's disease of the vulva (EMPDV). MATERIALS AND METHODS: This retrospective study included medical records and pathological slides of 18 female patients with EMPDV between January 2001 and December 2012. Diagnosis was confirmed using conventional hematoxylin and eosin staining. RESULTS: The median age was 65 years. The distribution of lesions was from labium majus, labium minus, clitoris, and distal vaginal wall. The appearance was erythematous patches, hypopigmentation, and hyperpigmentation. The symptoms were pruritus, erosions, burning sensation, and pain. The mean duration of symptoms was 24 months. Ten patients received local excision, 3 accepted wide local excisions and successful skin grafting, and 5 underwent vulvectomies. Frozen sections showed that 3 and 15 patients had positive and negative margins, respectively. The average length of follow-up was 70 months. During a follow-up period, 3 patients were lost. One patient with positive margins and one with negative margins recurred and the overall recurrence rate was 11.1%. CONCLUSION: The diagnosis of EMPDV is often delayed but has good prognosis. A complete surgical resection is an effective treatment. Skin grafting may be a good method to promote incision healing. PMID- 27661428 TI - Facial Treatment Preferences Among Aesthetically Oriented Men. AB - BACKGROUND: There is a paucity of data describing male attitudes toward age related changes to their facial features and associated preferences for prioritizing treatment. METHODS: Injectable-naive but aesthetically oriented men aged 30 to 65 participated in an online study (N = 600). Respondents indicated how concerned they were by the appearance of 15 age-related facial features, and the Maximum Difference scaling system was used to explore which features were most likely to be prioritized for treatment. The correlation between the features of most concern and the areas of treatment priority was assessed. Other aspects regarding the male perspective on aesthetic procedures, such as awareness, motivating factors, and barriers, also were explored. RESULTS: Crow's feet and tear troughs were rated as the most likely to be treated first (80% of first preferences) followed by forehead lines (74%), double chin (70%), and glabellar lines (60%). The areas of most concern in order were tear troughs, double chin, crow's feet, and forehead lines. There was a strong correlation between the features of most concern and the areas of treatment priority (r = 0.81). CONCLUSION: The periorbital areas, in particular crow's feet and tear troughs, are of most concern and likely to be prioritized for treatment among aesthetically oriented men. PMID- 27661430 TI - A New Subtype of Lichen Planopilaris Affecting Vellus Hairs and Clinically Mimicking Androgenetic Alopecia. AB - BACKGROUND: Lichen planopilaris (LPP) is a follicular variant of lichen planus. A new subtype of LPP mimicking androgenetic alopecia (AGA) may be misdiagnosed. Inappropriate medical therapy or hair transplantation may exacerbate this subtype. OBJECTIVE: To introduce clinicopathologic findings of a new subtype of LPP that selectively affects vellus hair in the pattern of AGA. MATERIALS AND METHODS: In a cross-sectional study, 433 (66.6%) men and 217 (33.4%) women with alopecia who were candidates of medical treatment or hair transplantation were included. Gross and microscopic attributes of their diseases were investigated. RESULTS: Among the total of 650 patients, 58 (8.9%; 95% confidence interval, 6.7% 11.1%) patients, including 52 women and 6 men, had LPP. We identified a distinct category of LPP presenting with diffuse hair loss in the pattern of AGA with predominant terminal hair, significant decrease in vellus hair, and minute punctuate scars in histopathology. Vellus hair follicles were the main sites of involvement. Perifollicular fibrosis and mild fibrosis with lichenoid lymphocytic infiltration around infundibular area of vellus hair follicles were present. CONCLUSION: There is a new form of LPP with clinical features similar to AGA. This form is histopathologically similar to LPP but selectively affects vellus hair follicles. PMID- 27661431 TI - Commentary on A New Subtype of Lichen Planopilaris Affecting Vellus Hairs and Clinically Mimicking Androgenetic Alopecia. PMID- 27661429 TI - ASDS Cosmetic Dermatologic Surgery Fellowship Milestones. AB - BACKGROUND: The American Council of Graduate Medical Education, which oversees much of postgraduate medical education in the United States, has championed the concept of "milestones," standard levels of achievement keyed to particular time points, to assess trainee performance during residency. OBJECTIVE: To develop a milestones document for the American Society for Dermatologic Surgery (ASDS) Cosmetic Dermatologic Surgery (CDS) fellowship program. METHODS: An ad hoc milestone drafting committee was convened that included members of the ASDS Accreditation Work Group and program directors of ASDS-approved Cosmetic Dermatologic Surgery (CDC) fellowship training programs. Draft milestones were circulated through email in multiple rounds until consensus was achieved. RESULTS: Thirteen milestones were developed in the 6 Accreditation Council for Graduate Medical Education (ACGME) competency areas, with 8 of these being patient-care milestones. Additional instructions for milestone administration more specific to the CDS fellowship than general ACGME instructions were also approved. Implementation of semiannual milestones was scheduled for the fellowship class entering in July 2018. CONCLUSION: Milestones are now available for CDS fellowship directors to implement in combination with other tools for fellow evaluation. PMID- 27661432 TI - Therapeutic Efficacy of Intralesional Steroid With Carbon Dioxide Laser Versus With Cryotherapy in Treatment of Keloids: A Randomized Controlled Trial. AB - BACKGROUND: Keloids are difficult to treat due to their poor response and high recurrence rate. OBJECTIVE: We conducted a randomized controlled trial to compare the therapeutic efficacy of intralesional triamcinolone acetonide (ILTA) in combination with carbon dioxide laser (Group 1) versus in combination with cryotherapy (Group 2) in the treatment of keloids. MATERIALS AND METHODS: Sixty patients with 101 keloids were randomized into 2 groups. On Day 1, keloids were ablated using either CO2 laser or cryotherapy followed by injection of ILTA at baseline and at 4 weeks interval for 3 months. Patients were followed up for 12 months to assess for therapeutic response and side effects. RESULTS: Successful therapeutic response (>50% improvement) between the 2 groups (CO2 vs cryotherapy) were assessed in terms of reduction in thickness, reduction in volume, patient's self-assessment, observer's assessment, and Vancouver Scar Scale score at the end of 6 months and 12 months (55.55% vs 70.37%; 61.1% vs 77.8%; 75% vs 77.78%; 61.12% vs 85.18%; 52.78% vs 62.96% respectively). The difference in therapeutic response between the 2 groups was not statistically significant at the end of 12 months. CONCLUSION: Both CO2 laser and cryotherapy in combination with ILTA were found to be equally effective in the treatment of keloids. PMID- 27661433 TI - Tissue Stabilized-Guided Subcision for the Treatment of Cellulite: A Multicenter Pivotal Study With Two-Year Follow-up. PMID- 27661434 TI - Birhombic Transposition Flap for Repair of Surgical Defects on the Nasal Dorsum. PMID- 27661435 TI - The Impact of Treatment on the Serum Concentration of Interleukin-1 Beta in Pulmonary Tuberculosis. AB - Tuberculosis (TB) is a major public health problem in the world. Further elucidation of the pathogenesis and identification of suitable biomarkers of the disease have remained research priorities. Interleukin-1 beta (IL-1 beta) signaling is known to be high in active tuberculosis. In this study, we followed up a cohort of adult sputum-positive tuberculosis patients and investigated the impact of anti-tuberculosis treatment on the serum concentrations of IL-1 beta. The protocol was approved by the Ethics Committee of University of Nigeria Teaching Hospital Enugu. Each participant gave informed consent. Serum concentration of Interleukin-1 was measured before treatment, after 2 months of treatment, and after 6 months of treatment by Enzyme linked immunosorbent assay method. Forty-two tuberculosis patients and 31 healthy volunteers completed the study. The patients had good clinical response to treatment. The mean serum concentration of Interleukin-1 beta (IL-1 beta) for the patients before treatment was very high (30.20 +/- 2.0 pg/mL) compared with those of healthy controls (13.30 +/- 1.30). As treatment progressed there was remarkable, progressive and statistically significant (P < 0.05) reduction in the mean IL-1 beta serum concentration of the patients: 21.80 +/- 1.1 pg/ml after 2 months and 16.96 +/- 1.3 pg/mL after 6 months treatment. At the completion of treatment, the mean serum concentration of IL-1 beta of the patients was comparable but slightly higher than those of the healthy controls. Serum concentration of Interleukin-1 beta is thus considered a potential host biomarker for active tuberculosis in adult humans. PMID- 27661436 TI - HPLC method development, validation, and impurity characterization of a potent antitumor nucleoside, T-dCyd (NSC 764276). AB - An HPLC method for the assay of an anticancer nucleoside, 4'-thio-2' deoxycytidine (T-dCyd, NSC 764276), has been developed and validated. The stress testing of T-dCyd was carried out in accordance with ICH guidelines Q1A (R2) under acidic, alkaline, oxidative, thermolytic, and photolytic conditions. The separation of T-dCyd from its impurities and degradation products was achieved in 40min on a Luna(r) Phenyl-Hexyl column (150mm*4.6mm i.d., 3MUm) with a gradient elution using ammonium phosphate buffer (pH 3.85) and methanol as the mobile phase. The gradient starts from 2% and ends at 80% of methanol. Detection is by UV at 282nm. LC-QTOF/MS was used to obtain mass data for characterization of impurities and degradation products. The proposed HPLC assay method was validated for specificity, linearity (concentration range 0.25-0.75mg/mL, r>=0.9998), accuracy (recovery 98.1-102.0%), precision (RSD<=1.5%), and sensitivity (LOD 0.1MUg/mL). The developed method was suitable for the quality control and stability monitoring of the T-dCyd drug substance. PMID- 27661437 TI - Catalytic Asymmetric Conjugate Addition and Sulfenylation of Diarylthiazolidin 2,4-diones. AB - This work reports the first application of diarylthiazolidin-2,4-diones as nucleophiles in asymmetric catalysis. By utilizing chiral amino acid-based (thio)urea-tertiary amines as the catalysts, we successively established asymmetric conjugate addition to nitroolefins and sulfenylation to N-(sulfanyl) succinimides of diarylthiazolidin-2,4-diones. Two series of biologically important 5-aryl-5-substituted thiazolidin-2,4-diones were obtained with high enantio- and diastereoselectivities (up to >99% ee and >19:1 dr). The enantioenriched adducts were found to show satisfactory anticancer activities against three different cancer cell lines using the MTT assay. All of these successes depended on the development of a general and expedient synthetic strategy to provide diverse 5H-thiazolidin-2,4-diones. PMID- 27661439 TI - Palliative care in the trauma ICU. AB - PURPOSE OF REVIEW: The benefits of palliative care for critically ill patients are well recognized, yet acceptance into surgical culture is lagging. With the increasing proportion of geriatric trauma patients, integration of palliative medicine within daily intensive care services to facilitate goal-concordant care is imperative. RECENT FINDINGS: Misconceptions of palliative medicine as it applies to trauma patients linger among trauma surgeons and many continue to practice without routine consultation of a palliative care service. Aggressive end-of-life care does not correlate with an improved family perception of medical care received near death. Additionally, elderly patients near the end of life often prefer palliative treatments over life-extending therapy, and their treatment preferences are often not achieved. A new geriatric-specific prognosis calculator estimates the risk of mortality after trauma, which is useful in starting goals of care discussions with older patients and their families. SUMMARY: Shifting our quality focus from 30-day mortality rates to measurements of symptom control and achievement of patient treatment preferences will prioritize patient beneficence and autonomy. Ownership of surgical palliative care as a service provided by acute care surgeons will ensure that our patients with incurable injury and illness will receive optimal patient-centered care. PMID- 27661438 TI - Alteration of the alertness-related network in patients with right temporal lobe epilepsy: A resting state fMRI study. AB - OBJECTIVES: This study aimed to investigate alterations in the alertness-related network in patients with right temporal lobe epilepsy (rTLE) and explore the functional mechanisms of impaired alertness. METHODS: We recruited twenty patients with rTLE and eighteen matched healthy controls. All participants took a neuropsychological attention network test (ANT) and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We extracted the alertness-related network using multiple independent component analysis (MICA). Subsequently, we compared the intergroup differences in functional connectivity (FC) of this network. Then, the neuropsychological data were correlated to voxels that showed significant FC differences in patients and controls. RESULTS: The alertness-related network extracted from the patients was similar to that of the controls, covering the right dorsolateral prefrontal cortex, middle frontal gyrus, parietal lobe, part of the temporal lobe, and left posterior lobe of the cerebellum (p<0.05). Compared to controls, patients with rTLE exhibited decreased FC values in the right inferior parietal lobe (IPL) and angular gyrus (p<0.05). Additionally, increased FC was shown in the right inferior frontal gyrus, Rolandic operculum, middle frontal gyrus, dorsolateral superior frontal gyrus, cuneus, and superior occipital gyrus (p<0.05). Behaviorally, patients with rTLE exhibited longer reaction times (RT) in the no cue (t=-2.07, p<0.05) and double cue (t=-2.28, p<0.05) conditions. However, the alertness effect in patients did not significantly differ from that of controls. Moreover, the alertness effect was negatively correlated with the mean Z-value in the right cuneus, which showed increased FC (r=-0.556, p=0.013) in patients with rTLE. There was no significant correlation in the control group. CONCLUSION: Our results demonstrated that alterations in the alertness-related network may contribute to the alertness impairment exhibited by patients with rTLE. Our study may provide new insights into the mechanisms of alertness impairments in rTLE. PMID- 27661440 TI - Medication-induced acute kidney injury. AB - PURPOSE OF REVIEW: The present article will review the current state of our understanding of nephrotoxic medication-associated acute kidney injury (AKI) and provide strategies to reduce its impact. RECENT FINDINGS: Nephrotoxic medications contribute to a substantial proportion of AKI in hospitalized patients. The previous perspective of nephrotoxic medication-associated AKI as a nonmodifiable necessary evil of providing appropriate therapy to ill patients had led to an incomplete understanding of its epidemiology and provided little impetus to reduce its occurrence. SUMMARY: Recent work on understanding specific combinations, thresholds for nephrotoxic burden and systematic kidney function assessment had mitigated, and even in some cases reduced, nephrotoxic AKI rates and severity. Current initiatives are underway to further refine specific nephrotoxic medication AKI risk via novel urinary biomarkers and genetic susceptibility. PMID- 27661442 TI - Virtual Screening for High Carrier Mobility in Organic Semiconductors. AB - Low carrier mobilities still hamper the use of organic semiconductors in many applications. Using a staged virtual screening approach we compute the electronic couplings and intramolecular reorganization energies as two main descriptors for charge mobility for a set of 95 445 molecular crystals extracted from the Cambridge Structural Database (CSD). As a final step, on the basis of the calculated coupling values, we identify materials with long-range charge percolation pathways. Thus we readily find many acclaimed compounds as well as a number of most promising materials that have not yet been considered for an application in organic electronics. Together with the unique metadata provided in the CSD, the large descriptor database allows us to extract important trends and correlations that will further accelerate the theoretical design and discovery of high mobility organic semiconductors. PMID- 27661441 TI - Human bloodstains on bone artefacts: an SEM intra- and inter-sample comparative study using ratite bird tibiotarsus. AB - Apart from their forensic significance in crime investigation, human bloodstains have an anthropological interest due to their occurrence on certain traditional weapons and ritual objects. Previously, a guiding study of erythrocytes in experimental samples including domestic sheep (Ovis aries) tibia was carried out using a scanning electron microscope (SEM). Here, a comparative SEM study to reveal the potential differences in bloodstain surface morphology as a function of intra-sample (smear region) and inter-sample (individual smear, smearing mechanism, bone origin) parameters is reported. A fragment of emu (Dromaius novaehollandiae) tibiotarsus was smeared with an adult man's peripheral blood. After air-drying and storing indoors, the boundary and neighbouring inner areas of the three individual bloodstains obtained were examined via secondary electrons in a variable-pressure SEM working in low-vacuum mode. As a whole, desiccation microcracks were present, the limits between the smear and the substrate appeared poorly defined, and no erythrocyte negative replicas were observed in the examined areas. In addition, a putative fibrin network, more or less embedded in the dried plasma matrix, was observed in the smears' boundary. Regarding the smear region in sliding smears, the periphery and boundary revealed to be different, while the head and tail were similar. Considering individual sliding smears, they had similar characteristics. Relating to the smear region as a function of the smearing mechanism, the periphery was different whether sliding or touching, while the boundary was similar in sliding and touching smears. Concerning the smear region as a function of the bone origin, the periphery revealed to be similar in both ratite and mammalian bone, while the boundary did different in ratite and mammalian bone. The results of this study show that SEM examination can be used fruitfully to detect bloodstains on ratite bone. Combined with previous SEM results in domestic sheep bone, they suggest, further, that blood remains can be detected on objects made of bone irrespectively of the mammalian or ratite origin of this raw material. PMID- 27661443 TI - Phage Display Technology in Biomaterials Engineering: Progress and Opportunities for Applications in Regenerative Medicine. AB - The field of regenerative medicine has been gaining momentum steadily over the past few years. The emphasis in regenerative medicine is to use various in vitro and in vivo approaches that leverage the intrinsic healing mechanisms of the body to treat patients with disabling injuries and chronic diseases such as diabetes, osteoarthritis, and degenerative disorders of the cardiovascular and central nervous system. Phage display has been successfully employed to identify peptide ligands for a wide variety of targets, ranging from relatively small molecules (enzymes, cell receptors) to inorganic, organic, and biological (tissues) materials. Over the past two decades, phage display technology has advanced tremendously and has become a powerful tool in the most varied fields of research, including biotechnology, materials science, cell biology, pharmacology, and diagnostics. The growing interest in and success of phage display libraries is largely due to its incredible versatility and practical use. This review discusses the potential of phage display technology in biomaterials engineering for applications in regenerative medicine. PMID- 27661444 TI - Copper-Catalyzed Three-Component System for Arylsulfenylation of Imidazopyridines with Elemental Sulfur. AB - A one-pot three-component reaction for the regioselective synthesis of thioarylated imidazoheterocycles from aryl halides and elemental sulfur using copper(I) iodide as a catalyst has been developed. Reactions proceed with high efficiency and afford thioarylated imidazoheterocycles in good yields with broad functional group tolerance. PMID- 27661445 TI - Ground-State Charge Transfer: Lithium-Benzene and the Role of Hartree-Fock Exchange. AB - Most approximations to the exchange-correlation functional of Kohn-Sham density functional theory lead to delocalization errors that undermine the description of charge-transfer phenomena. We explore how various approximate functionals and charge-distribution schemes describe ground-state atomic-charge distributions in the lithium-benzene complex, a model system of relevance to carbon-based supercapacitors. To understand the trends, we compare Hartree-Fock (HF) and correlated post-HF calculations, confirming that the HOMO-LUMO gap is narrower in semilocal functionals but widened by hybrid functionals with large fractions of HF exchange. For semilocal functionals, natural bond orbital (NBO) and Mulliken schemes yield opposite pictures of how charge transfer occurs. In PBE, for example, when lithium and benzene are <1.5 A apart, NBO yields a positive charge on the lithium atom, but the Mulliken scheme yields a negative charge. Furthermore, the partial charges in conjugated materials depend on the interplay between the charge-distribution scheme employed and the underlying exchange correlation functional, being critically sensitive to the admixture of HF exchange. We analyze and explain why this happens, discuss implications, and conclude that hybrid functionals with an admixture of about one-fourth of HF exchange are particularly useful in describing charge transfer in the lithium benzene model. PMID- 27661446 TI - Synthesis and Characterization of Pt-Ag Alloy Nanocages with Enhanced Activity and Durability toward Oxygen Reduction. AB - Engineering the elemental composition of metal nanocrystals offers an effective strategy for the development of catalysts or electrocatalysts with greatly enhanced activity. Herein, we report the synthesis of Pt-Ag alloy nanocages with an outer edge length of 18 nm and a wall thickness of about 3 nm. Such nanocages with a composition of Pt19Ag81 could be readily prepared in one step through the galvanic replacement reaction between Ag nanocubes and a Pt(II) precursor. After 10 000 cycles of potential cycling in the range of 0.60-1.0 V as in an accelerated durability test, the composition of the nanocages changed to Pt56Ag44, together with a specific activity of 1.23 mA cm-2 toward oxygen reduction, which was 3.3 times that of a state-of-the-art commercial Pt/C catalyst (0.37 mA cm-2) prior to durability testing. Density functional theory calculations attributed the increased activity to the stabilization of the transition state for breaking the O-O bond in molecular oxygen. Even after 30 000 cycles of potential cycling, the mass activity of the nanocages only dropped from 0.64 to 0.33 A mg-1Pt, which was still about two times that of the pristine Pt/C catalyst (0.19 A mg-1Pt). PMID- 27661447 TI - MOF-74 as an Efficient Catalyst for the Low-Temperature Selective Catalytic Reduction of NOx with NH3. AB - In this work, Mn-MOF-74 with hollow spherical structure and Co-MOF-74 with petal like shape have been prepared successfully via the hydrothermal method. The catalysts were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry-mass spectrum analysis (TG-MS), N2 adsorption/desorption, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). It is found that MOF-74(Mn, Co) exhibits the capability for selective catalytic reduction (SCR) of NOx at low temperatures. Both experimental (temperature-programmed desorption, TPD) and computational methods have shown that Co-MOF-74 and Mn-MOF-74 owned high adsorption and activation abilities for NO and NH3. The catalytic activities of Mn-MOF-74 and Co MOF-74 for low-temperature denitrification (deNOx) in the presence of NH3 were 99% at 220 degrees C and 70% at 210 degrees C, respectively. It is found that the coordinatively unsaturated metal sites (CUSs) in M-MOF-74 (M = Mn and Co) played important roles in SCR reaction. M-MOF-74 (M = Mn and Co), especially Mn MOF-74, showed excellent catalytic performance for low-temperature SCR. In addition, in the reaction process, NO conversion on Mn-MOF-74 decreased with the introduction of H2O and SO2 and almost recovered when gas was cut off. However, for Co-MOF-74, SO2 almost has no effect on the catalytic activity. This work showed that MOF-74 could be used prospectively as deNOx catalyst. PMID- 27661451 TI - The role of docetaxel in the treatment of non-small cell lung cancer lung cancer: an update. AB - INTRODUCTION: Non-small cell lung cancer lung cancer (NSCLC) is a devastating disease, with poor prognosis for patients with metastatic disease. The management of these patients has evolved during the past decade, challenging the role of cytotoxic chemotherapy as the only available treatment option. Nevertheless, chemotherapy still retains a dominant position for the majority of both treatment naive and pretreated patients. Among the chemotherapeutic agents, docetaxel is one of the most commonly used in 1st and subsequent treatment lines, even in the current era of precision medicine. Areas covered: We searched Medline, Embase, Scopus and Cochrane Library for randomized phase III trials that evaluated docetaxel in various clinical settings of NSCLC and for meta-analyses of such trials and we present all relevant data regarding the pharmacology and clinical use of docetaxel in NSCLC. Expert commentary: Despite its diminishing role, docetaxel in combination with novel targeted agents remains an important option of the therapeutic armamentarium in advanced NSCLC. PMID- 27661448 TI - Two missense mutations in SALL4 in a patient with microphthalmia, coloboma, and optic nerve hypoplasia. AB - To investigate the genetic etiology of anophthalmia and microphthalmia, we used exome sequencing in a Caucasian female with unilateral microphthalmia and coloboma, bilateral optic nerve hypoplasia, ventricular and atrial septal defects, and growth delays. We found two sequence variants in SALL4 - c.[575C>A], predicting p.(Ala192Glu), that was paternally inherited, and c.[2053G>C], predicting p.(Asp685His), that was maternally inherited. Haploinsufficiency for SALL4 due to nonsense or frameshift mutations has been associated with acro-renal ocular syndrome that is characterized by eye defects including Duane anomaly and coloboma, in addition to radial ray malformations and renal abnormalities. Our report is the first description of structural eye defects associated with two missense variants in SALL4 inherited in trans; the absence of reported findings in both parents suggests that both sequence variants are hypomorphic mutations and that both are needed for the ocular phenotype. SALL4 is expressed in the developing lens and regulates BMP4, leading us to speculate that altered BMP4 expression was responsible for the eye defects, but we could not demonstrate altered BMP4 expression in vitro after using small interfering RNAs (siRNAs) to reduce SALL4 expression. We conclude that SALL4 hypomorphic variants may influence eye development. PMID- 27661449 TI - Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis. AB - PAS domain containing protein kinase (Pask) is an evolutionarily conserved protein kinase implicated in energy homeostasis and metabolic regulation across eukaryotic species. We now describe an unexpected role of Pask in promoting the differentiation of myogenic progenitor cells, embryonic stem cells and adipogenic progenitor cells. This function of Pask is dependent upon its ability to phosphorylate Wdr5, a member of several protein complexes including those that catalyze histone H3 Lysine 4 trimethylation (H3K4me3) during transcriptional activation. Our findings suggest that, during myoblast differentiation, Pask stimulates the conversion of repressive H3K4me1 to activating H3K4me3 marks on the promoter of the differentiation gene myogenin (Myog) via Wdr5 phosphorylation. This enhances accessibility of the MyoD transcription factor and enables transcriptional activation of the Myog promoter to initiate muscle differentiation. Thus, as an upstream kinase of Wdr5, Pask integrates signaling cues with the transcriptional network to regulate the differentiation of progenitor cells. PMID- 27661450 TI - A robust activity marking system for exploring active neuronal ensembles. AB - Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system's versatility. PMID- 27661453 TI - Respite service use among caregivers of older people: comparative analysis of family dementia caregivers with musculoskeletal and circulatory system disorder caregivers. AB - OBJECTIVES: To identify the main drivers of the use of respite services and the need for respite services among caregivers of people experiencing dementia relative to family caregivers of people with other health conditions. METHOD: Based on nationally representative secondary data regression analysis was used to test the association between selected health conditions and the utilisation of and need for respite services. RESULTS: For a person living with dementia the odds of using respite care are higher than for a person with either a musculoskeletal or circulatory condition. Family caregivers of people living with dementia report the odds of the need for more respite as 5.3 times higher than for family caregivers of people with musculoskeletal conditions and 7.7 times higher than for family caregivers of people with circulatory conditions. The main reason for never using respite services is largely driven by the type of health condition, age of care recipient, existence of a spouse, and level of disability. CONCLUSIONS: Respite services that cater to the specific needs of families experiencing dementia at home should become a higher priority within the aged care sector. Alternative models of respite care that focus on prevention and early intervention would be cost effective. PMID- 27661452 TI - Profiling of adhesive-related genes in the freshwater cnidarian Hydra magnipapillata by transcriptomics and proteomics. AB - The differentiated ectodermal basal disc cells of the freshwater cnidarian Hydra secrete proteinaceous glue to temporarily attach themselves to underwater surfaces. Using transcriptome sequencing and a basal disc-specific RNA-seq combined with in situ hybridisation a highly specific set of candidate adhesive genes was identified. A de novo transcriptome assembly of 55,849 transcripts (>200 bp) was generated using paired-end and single reads from Illumina libraries constructed from different polyp conditions. Differential transcriptomics and spatial gene expression analysis by in situ hybridisation allowed the identification of 40 transcripts exclusively expressed in the ectodermal basal disc cells. Comparisons after mass spectrometry analysis of the adhesive secretion showed a total of 21 transcripts to be basal disc specific and eventually secreted through basal disc cells. This is the first study to survey adhesion-related genes in Hydra. The candidate list presented in this study provides a platform for unravelling the molecular mechanism of underwater adhesion of Hydra. PMID- 27661455 TI - Ossicular replacement prostheses from banked bone with ergonomic and functional geometry. AB - This study shows the fabrication of innovative ossicular replacement prostheses (ORPs) based on banked cortical bone using computer numerically controlled ultraprecision micromilling, as a substantial improvement of "second generation" ORPs. Our aim is to combine optimal middle ear compatibility and surgical manageability in a single device, by releasing off-the-shelf homograft ORPs provided with the appealing features of synthetic ORPs, such as lightness, safety, measurement accuracy, surface decoration, and geometric plasticity. The new total ORP prototype was 13.1 +/- 0.1 mg, leading to 81% weight reduction with respect to the previous model. Surface motifs of the head plate were applied to prevent slipping and migration after surgery, as shown by finite element modeling analysis. In addition, bone ORPs were provided with holed head plates to facilitate their surgical positioning while reducing their mass. A comparative measurement of acoustic responses of bone against synthetic partial ORPs in the 250-8000 Hz frequency range demonstrated their superior behavior. This study showed that banked compact bone can be optimally manufactured, eventually enabling the fabrication of light, standardized, and highly performant ORPs. The new bone ORPs may represent the ideal combination of biocompatibility and technology which can ultimately accomplish unmet otosurgical needs. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2495 2506, 2017. PMID- 27661456 TI - Pd-Catalyzed Carboamination of Alkylidenecyclopropanes: Synthesis of Congested Pyrrolidines and Piperidines. AB - The synthesis of densely functionalized N-heterocycles is an ongoing challenge in chemical synthesis. Herein, we report an efficient method for the construction of pyrrolidine and piperidine scaffolds using a palladium-catalyzed carboamination of alkylidenecyclopropanes. PMID- 27661454 TI - Improved decision making for prioritizing tumor targeting antibodies in human xenografts: Utility of fluorescence imaging to verify tumor target expression, antibody binding and optimization of dosage and application schedule. AB - Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome. To overcome these problems, we have used different fluorescence-labeled therapeutic antibodies targeting human epidermal growth factor receptor (HER) family members and insulin-like growth factor-1 receptor (IGF1R) in combination with fluorescence imaging modalities to determine tumor antigen expression, drug-target interaction, and biodistribution and tumor saturation kinetics in non-small cell lung cancer xenografts. For this, whole body fluorescence intensities of labeled antibodies, applied as a single compound or antibody mixture, were measured in Calu-1 and Calu-3 tumor-bearing mice, then ex vivo multispectral tumor tissue analysis at microscopic resolution was performed. With the aid of this simple and fast imaging method, we were able to analyze the tumor cell receptor status of HER1-3 and IGF1R, monitor the antibody target interaction and evaluate the receptor binding sites of anti-HER2-targeting antibodies. Based on this, the most suitable tumor model, best therapeutic antibody, and optimal treatment dosage and application schedule was selected. Predictions drawn from obtained imaging data were in excellent concordance with outcome of conducted preclinical efficacy studies. Our results clearly demonstrate the great potential of combined in vivo and ex vivo fluorescence imaging for the preclinical development and characterization of monoclonal antibodies. PMID- 27661457 TI - Is involvement of inflammation underestimated in Pelizaeus-Merzbacher disease? AB - Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating leukodystrophy resulting from proteolipid protein 1 gene (PLP1) mutations leading to oligodendrocyte loss. While neuroinflammation has recently become a common feature and actor in neurodegenerative diseases, the involvement of inflammation in PMD physiopathology is still highly debated despite evidence for strong astrogliosis and microglial cell activation. Activation of the innate immune system, and more particularly, of microglia and astrocytes, is mostly associated with the deleterious role of neuroinflammation. However, in diseases such as multiple sclerosis, microglia appear beneficial for repair based on their role in myelin debris removal or recruitment and differentiation of oligodendrocyte progenitor cells. In this review, we will discuss recent published data in terms of their relevance to the role of microglia in PMD evolution, and of their impact on the improvement of therapeutic approaches combining immunomodulation and cell therapy to promote optimal recovery. (c) 2016 Wiley Periodicals, Inc. PMID- 27661458 TI - Use of intravoxel incoherent motion diffusion-weighted imaging in identifying the vascular and avascular zones of human meniscus. AB - PURPOSE: To investigate the hypothesis that the intravoxel incoherent motion (IVIM) diffusion-weighted imaging may depict microcirculation of meniscus and the perfusion changes in meniscal disorder. MATERIALS AND METHODS: Fifty patients received diffusion-weighted MRI with multiple b-values ranging from 0 to 400 s/mm2 . The four horns of the menisci were divided into normal, degenerated, and torn groups. IVIM parameters including perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D), and the product of f and D* (f D*) of normal meniscal red zone and white zone were derived and compared for microcirculation changes of normal, degenerated, and torn posterior horn of the medial meniscus (PMM). The parameters between red and white zones among the groups were compared. Significant differences were considered when P < 0.05. RESULTS: Mean f and fD* were significantly higher in the red zone than those in the white zone for the normal four meniscal horns (P < 0.05), whereas D* (P = 0.882, 0.011, 0.593, and 0.33) and D (P = 0.186, 0.099, 0.767, and 0.041) did not significantly differ between the two zones. Among the normal, degenerated, and torn PMM, f was observed to be lower in the red zone of torn horns as compared to the normal horns (P = 0.013). D*, fD*, and D did not exhibit statistically significant difference among different groups (P = 0.353, 0.661, and 0.327, respectively). CONCLUSION: This hypothesis driven work shows that IVIM imaging is able to depict microcirculation of meniscus and the perfusion changes in meniscal disorder. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:1090-1096. PMID- 27661460 TI - Zinc-Reduced Mesoporous TiOx Li-Ion Battery Anodes with Exceptional Rate Capability and Cycling Stability. AB - We demonstrate a unique synthetic route for oxygen-deficient mesoporous TiOx by a redox-transmetalation process by using Zn metal as the reducing agent. The as obtained materials have significantly enhanced electronic conductivity; 20 times higher than that of as-synthesized TiO2 material. Moreover, electrochemical impedance spectroscopy (EIS) and galvanostatic intermittent titration technique (GITT) measurements are performed to validate the low charge carrier resistance of the oxygen-deficient TiOx . The resulting oxygen-deficient TiOx battery anode exhibits a high reversible capacity (~180 mA h g-1 at a discharge/charge rate of 1 C/1 C after 400 cycles) and an excellent rate capability (~90 mA h g-1 even at a rate of 10 C). Also, the full cell, which is coupled with a LiCoO2 cathode material, exhibits an outstanding rate capability (>75 mA h g-1 at a rate of 3.0 C) and maintains a reversible capacity of over 100 mA h g-1 at a discharge/charge of 1 C/1 C for 300 cycles. PMID- 27661459 TI - PACAP and VIP Inhibit HIF-1alpha-Mediated VEGF Expression in a Model of Diabetic Macular Edema. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert a protective role against retinal injuries, including diabetic macular edema (DME). The macular damage is induced by hyperglycemia, which damages vessels supplying blood to the retina and induces hypoxia. The microenvironmental changes stimulate the expression of hypoxia inducible factors (HIFs), which promote the choroidal endothelial cell transmigration across the retinal pigmented epithelium (RPE) into neurosensory retina, where they proliferate into new vessels under stimulation of the vascular endothelial growth factor (VEGF). In the present study, we have investigated whether PACAP and VIP prevent retinal damage by modulating the expression of HIFs, VEGF, and its receptors. In accord to our hypothesis, we have shown that both peptides are able to significantly reduce HIF-1alpha and increase HIF-3alpha expression in ARPE-19 cells exposed to hyperglycemic/hypoxic insult. This effect is also related to a reduction of VEGF and its receptors expression. Moreover, both peptides also reduce the activation of p38 mitogen-activated protein kinase (MAPK), a pro-apoptotic signaling pathway, which is activated by VEGFR-1 and 2 receptors. In conclusion, our study has further elucidated the protective role performed by PACAP and VIP, against the harmful combined effect of hyperglycemia/hypoxia characterizing the DME microenvironment. J. Cell. Physiol. 232: 1209-1215, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27661461 TI - Causes and consequences of large clonal assemblies in a poplar hybrid zone. AB - Asexual reproduction is a common and fundamental mode of reproduction in plants. Although persistence in adverse conditions underlies most known cases of clonal dominance, proximal genetic drivers remain unclear, in particular for populations dominated by a few large clones. In this study, we studied a clonal population of the riparian tree Populus alba in the Douro river basin (northwestern Iberian Peninsula) where it hybridizes with Populus tremula, a species that grows in highly contrasted ecological conditions. We used 73 nuclear microsatellites to test whether genomic background (species ancestry) is a relevant cause of clonal success, and to assess the evolutionary consequences of clonal dominance by a few genets. Additional genotyping-by-sequencing data were produced to estimate the age of the largest clones. We found that a few ancient (over a few thousand years old) and widespread genets dominate the population, both in terms of clone size and number of sexual offspring produced. Interestingly, large clones possessed two genomic regions introgressed from P. tremula, which may have favoured their spread under stressful environmental conditions. At the population level, the spread of large genets was accompanied by an overall ancient (>0.1 Myr) but soft decline of effective population size. Despite this decrease, and the high clonality and dominance of sexual reproduction by large clones, the Douro hybrid zone still displays considerable genetic diversity and low inbreeding. This suggests that even in extreme cases as in the Douro, asexual and sexual dominance of a few large, geographically extended individuals does not threaten population survival. PMID- 27661462 TI - Fungal endophytes of South China blueberry (Vaccinium dunalianum var. urophyllum). AB - : A total of 374 fungal endophyte strains were isolated from of Vaccinium dunalianum var. urophyllum (Ericaceae), a well-known cultivated blueberry in southern China. These fungal endophytes could be categorized into 25 morphotypes according to culture characteristics and molecular identification based on the internal transcribed spacer region. All of these isolates belonged to Ascomycota. Jaccard's (Jc) and Sorenson's similarity indices indicated that the species communities from the fruits and branches were closer to each other than to those from leaves. The leaves appeared to host the highest fungal biodiversity, and the fruits displayed the lowest diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first on endophytic fungi isolated from fruits, branches and leaves of blueberry plants. The results contribute to the body of knowledge on the biocontrol of pathogens associated with blueberry and develop the improvement of plant growth. By comparing with the different fungal communities, the leaves appeared to host the highest biodiversity. PMID- 27661463 TI - Improved hybrid/GPU algorithm for solving cardiac electrophysiology problems on Purkinje networks. AB - Cardiac Purkinje fibers provide an important pathway to the coordinated contraction of the heart. We present a numerical algorithm for the solution of electrophysiology problems across the Purkinje network that is efficient enough to be used in in silico studies on realistic Purkinje networks with physiologically detailed models of ion exchange at the cell membrane. The algorithm is on the basis of operator splitting and is provided with 3 different implementations: pure CPU, hybrid CPU/GPU, and pure GPU. Compared to our previous work, we modify the explicit gap junction term at network bifurcations to improve its mathematical consistency. Due to this improved consistency of the model, we are able to perform an empirical convergence study against analytical solutions. The study verified that all 3 implementations produce equivalent convergence rates, and shows that the algorithm produces equivalent result across different hardware platforms. Finally, we compare the efficiency of all 3 implementations on Purkinje networks of increasing spatial resolution using membrane models of increasing complexity. Both hybrid and pure GPU implementations outperform the pure CPU implementation, but their relative performance difference depends on the size of the Purkinje network and the complexity of the membrane model used. PMID- 27661464 TI - Do surgical interventions for limb lymphoedema reduce cellulitis attack frequency? AB - INTRODUCTION: Recurrent cellulitis is a frequent and challenging complication of lymphoedema. British Lymphology Society cellulitis guidelines state that decongestive lymphatic therapy reduces the frequency of cellulitis attacks, but do not mention the effect of surgical interventions. This systematic review aims to assess whether surgical interventions for lymphoedema reduce the frequency of attacks of cellulitis. MATERIALS AND METHODS: Embase, Medline, and the Cochrane database were searched for relevant articles from database inception to January 2016. Four hundred and thirty-six abstracts were retrieved. Studies were included which contained quantitative data on cellulitis incidence before and after a surgical intervention. Two independent reviewers applied selection criteria, selecting 27 papers for full text review. Two were unavailable in the UK from any source. RESULTS: A variety of surgical techniques were utilized in the 25 papers included: lymphaticovenous anastomosis, superficial-to-deep lymphaticolymphatic anastomosis, lymph node transfer, Charles procedure, muscle flap transfer, Homan's procedure, and subcutaneous tissue excision below skin flaps. Five studies combined techniques. One study compared the intervention to a control group (physical therapy). Cellulitis incidence was decreased following surgical intervention in 24/25 studies included. Eight had quantifiable reductions in cellulitis over a set follow-up period; in the other 16 preoperative incidence was not precisely defined. CONCLUSION: Surgery appears effective at reducing cellulitis incidence in lymphoedema. However, high quality evidence from randomized controlled trials is lacking. Future research should concentrate on comparison with control groups, for example compression alone versus compression with surgical intervention, in patients with lymphoedema and greater than two attacks of cellulitis per year. PMID- 27661465 TI - The last bastion? X chromosome genotyping of Anopheles gambiae species pair males from a hybrid zone reveals complex recombination within the major candidate 'genomic island of speciation'. AB - Speciation with gene flow may be aided by reduced recombination helping to build linkage between genes involved in the early stages of reproductive isolation. Reduced recombination on chromosome X has been implicated in speciation within the Anopheles gambiae complex, species of which represent the major Afrotropical malaria vectors. The most recently diverged, morphologically indistinguishable, species pair, A. gambiae and Anopheles coluzzii, ubiquitously displays a 'genomic island of divergence' spanning over 4 Mb from chromosome X centromere, which represents a particularly promising candidate region for reproductive isolation genes, in addition to containing the diagnostic markers used to distinguish the species. Very low recombination makes the island intractable for experimental recombination studies, but an extreme hybrid zone in Guinea Bissau offers the opportunity for natural investigation of X-island recombination. SNP analysis of chromosome X hemizygous males revealed: (i) strong divergence in the X-island despite a lack of autosomal divergence; (ii) individuals with multiple recombinant genotypes, including likely double crossovers and localized gene conversion; (iii) recombination-driven discontinuity both within and between the molecular species markers, suggesting that the utility of the diagnostics is undermined under high hybridization. The largely, but incompletely protected nature of the X centromeric genomic island is consistent with a primary candidate area for accumulation of adaptive variants driving speciation with gene flow, while permitting some selective shuffling and removal of genetic variation. PMID- 27661467 TI - The marketing potential of corporate social responsibility activities: the case of the alcohol industry in Latin America and the Caribbean. AB - AIMS: The aims were to: (1) identify, monitor and analyse the Corporate Social Responsibility (CSR) practices of the alcohol industry in Latin America and the Caribbean (LAC) and (2) examine whether the alcohol industry is using these actions to market their products and brands. METHODS: Nine health experts from Argentina, Brazil and Uruguay conducted a content analysis of 218 CSR activities using a standardized protocol. A content rating procedure was used to evaluate the marketing potential of CSR activities as well as their probable population reach and effectiveness. The LEAD procedure (longitudinal, expert and all data) was applied to verify the accuracy of industry-reported descriptions. RESULTS: A total of 55.8% of the actions were found to have a marketing potential, based on evidence that they are likely to promote brands and products. Actions with marketing potential were more likely to reach a larger audience than actions classified with no marketing potential. Most actions did not fit into any category recommended by the World Health Organization; 50% of the actions involving classroom and college education for young people were found to have marketing potential; 62.3% were classified as meeting the definition of risk management CSR. CONCLUSION: Alcohol industry Corporate Social Responsibility activities in Latin America and the Caribbean appear to have a strategic marketing role beyond their stated philanthropic and public health purpose. PMID- 27661466 TI - Changes in plasma levels of oxidized lipoproteins and lipoprotein subfractions with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy and associations with common carotid artery intima-media thickness: ACTG 5260s. AB - BACKGROUND: The role of oxidized lipoproteins (high-density [HDLox] and low density [LDLox]) and total lipoprotein particle (Lp) number and size in HIV related cardiovascular disease (CVD) is unclear. The goal of this study was to evaluate changes of these biomarkers and their associations with rate of carotid intima media thickness progression over 3 years (DeltaCIMT) in chronic HIV infection. METHODS: Prospective study of 234 HIV-infected antiretroviral treatment-naive participants without CVD who were randomized to receive tenofovir emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir or raltegravir (RAL) and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter. Biomarker changes over 24, 48 or 96 weeks from baseline and pairwise treatment group comparisons were examined. Associations of these biomarkers with DeltaCIMT were analysed with mixed effects linear regression. RESULTS: HDLp number increased with both protease inhibitors (PIs) over 48 weeks, while LDLp number declined with RAL; Lp size did not change. Over 96 weeks, normalized HDLox declined with both PIs; LDLox increased in all groups. Few treatment group differences were observed across all biomarkers. Associations between DeltaCIMT and oxidized lipoproteins at all time points were not apparent (P>=0.10). There was some evidence of slower DeltaCIMT for higher HDLp number (P=0.06) and for lower LDLp number (P=0.08) measured at baseline. CONCLUSIONS: Unexpectedly, LDLox increased modestly in all treatment groups after ART initiation. Associations of plasma HDLox and LDLox with DeltaCIMT were not apparent. While plasma levels of abnormal lipoproteins have been shown to be associated with CVD outcomes, clear associations with sub-clinical atherosclerosis progression were not apparent in our study. PMID- 27661468 TI - The Cajal body and the nucleolus: "In a relationship" or "It's complicated"? AB - From their initial identification as 'nucleolar accessory bodies' more than a century ago, the relationship between Cajal bodies and nucleoli has been a subject of interest and controversy. In this review, we seek to place recent developments in the understanding of the physical and functional relationships between the 2 structures in the context of historical observations. Biophysical models of nuclear body formation, the molecular nature of CB/nucleolus interactions and the increasing list of joint roles for CBs and nucleoli, predominantly in assembling ribonucleoprotein (RNP) complexes, are discussed. PMID- 27661472 TI - Health Literacy Is Associated With Health Behaviors and Social Factors Among Older Adults: Results from the LifeLines Cohort Study. AB - This study assesses the associations between health literacy and various health behaviors and social factors among older adults, and whether social factors moderate the other associations. Data from 3,241 participants in the LifeLines Cohort Study were analyzed (mean baseline age = 68.9 years). Data on health literacy, health behaviors (physical activity, fruit and vegetable consumption, smoking, breakfast consumption, alcohol consumption, and body mass index (BMI), and social factors (loneliness, social support, social activities, social contacts, and living situation) were collected in three waves. Logistic regression analyses were used, adjusted for age and gender. Low health literacy was associated with insufficient physical activity, insufficient fruit and vegetable consumption, lack of regular breakfast consumption, obesity (odds ratios (ORs) > 1.31, p-values < .005) and low alcohol use (OR = 0.81, p = .013), but not with smoking. Low health literacy was also associated with greater loneliness, engaging in fewer social activities, and having fewer social contacts (ORs > 1.48, p-values < .005), but not with social support or living situation. Only the association between health literacy and smoking was moderated by social contacts, but this finding needs confirmation in future studies. In conclusion, low health literacy is negatively associated with health behaviors and social factors in older adults, but social factors seldom moderate the associations between health literacy and health behaviors. PMID- 27661469 TI - The Effect of Chair Yoga on Biopsychosocial Changes in English- and Spanish Speaking Community-Dwelling Older Adults with Lower-Extremity Osteoarthritis. AB - Chair yoga (CY), a mind-body therapy, is a safe nonpharmacological approach for managing osteoarthritis (OA) in older adults who cannot participate in standing exercise. However, there is no linguistically tailored CY program for those with limited English proficiency (LEP). This 2-arm randomized controlled trial compared the effects of a linguistically tailored yoga program (English and Spanish versions) on the outcomes of pain, physical function, and psychosocial factors compared to the effects of a linguistically tailored Health Education Program (HEP; English and Spanish versions). Participants with lower-extremity OA, recruited from 2 community sites, completed the Spanish (n = 40) or English (n = 60) version of twice-weekly 45-min CY or HEP sessions for 8 weeks. Data were collected at baseline, 4 weeks, 8 weeks, and 1- and 3-month follow-ups. English and Spanish CY groups (but neither HEP language group) showed significant decreases in pain interference. Measures of OA symptoms, balance, depression, and social activities were not significantly different between English and Spanish versions of CY and English and Spanish versions of HEP. It was concluded that the Spanish and English versions of CY and HEP were equivalent. Linguistically tailored CY could be implemented in aging-serving communities for persons with LEP. PMID- 27661473 TI - Mortality in Patients Admitted for Concurrent COPD Exacerbation and Pneumonia. AB - It is unclear whether concurrent pneumonia and chronic obstructive pulmonary disease (COPD) have a higher mortality than either condition alone. Further, it is unknown how this interaction changes over time. We explored the effect of pneumonia and COPD on inpatient, 30-day and overall mortality. We used a Veterans Health Affairs database to compare patients who were hospitalized for a COPD exacerbation without pneumonia (AECOPD), patients hospitalized for pneumonia without COPD (PNA) and patients hospitalized for pneumonia who had a concurrent diagnosis of COPD (PCOPD). We studied records of 15,065 patients with the following primary discharge diagnoses: (a) AECOPD cohort (7,154 individuals); (b) PNA cohort (4,433 individuals); and (c) PCOPD (3,478 individuals), comparing inpatient, 30-day and overall mortality in the three study cohorts. We observed a stepwise increase in inpatient mortality for AECOPD, PNA and PCOPD (4.8%, 9.5% and 13.2%, respectively). These differences persisted at 30 days post-discharge (AECOPD = 6.7%, PNA = 12.4% and PCOPD = 14.6%; p < 0.0001), but not throughout the study period (median follow-up: 37 months). With time, the death rate rose disproportionally in patients who had been admitted for AECOPD (AECOPD = 64.5%; PNA = 57.4% and PCOPD 66.2%; p < 0.001). In multivariate analysis, PCOPD predicted the greatest inpatient mortality (p < 0.001). The data showed a progression in inpatient and 30-day mortality from AECOPD to PNA to PCOPD. Pneumonia and COPD differentially affected inpatient, 30-day and overall mortality with pneumonia affecting predominantly inpatient and 30-day mortality while COPD affecting the overall mortality. PMID- 27661470 TI - Self-Reported Ecstasy/MDMA/"Molly" Use in a Sample of Nightclub and Dance Festival Attendees in New York City. AB - BACKGROUND: Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of "Molly," which is often marketed as pure MDMA. Surveys have generally not included "Molly" in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use-nightlife attendees. METHODS: We surveyed 679 young adults (age 18-25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. RESULTS: Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR = 0.37, p = .015). Over a third of ecstasy users (36.8%)reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones ["bath salts"]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. CONCLUSION: A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name). PMID- 27661475 TI - Taking action on jobs. AB - TheNurses workcampaign sparked national and regional publicity throughout the United Kingdom last week, with press launches in England, Wales, Scotland and Northern Ireland. Hundreds of nurses have applied for a free campaign pack* - confirming that there are many out there who fear for their jobs. PMID- 27661476 TI - Tissue viability society. AB - The Tissue Viability Society, founded ment, 1981 as a branch of the Wessex terly Rehabilitation Association, was orig- welcomes concerned with the prevention and all of pressure sores. It has developed Further Tel: a unique forum for considering all aspects from the problems of tissue viability. Its membership is open to all who have a common Odstock in rehabilitation and wound care. PMID- 27661474 TI - Hierarchical Structure and Cross-Cultural Measurement Invariance of the Norwegian Version of the Personality Inventory for DSM-5. AB - : The Personality Inventory for DSM-5 (PID-5) was created to aid a trait-based diagnostic system for personality disorders (PDs) in the Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013a ). In this study, we aimed to evaluate the Norwegian version of the PID-5 by examining its score reliability, hierarchical structure, congruency with international findings, and cross-cultural measurement invariance with a matched U.S. SAMPLE: For this purpose, 503 university students (76% females) were administered the PID-5. The Norwegian PID-5 showed good score reliability and structural validity from 1 to 5 factors. The 5-factor structure was generally congruent with international findings, and support for measurement invariance across the Norwegian and a matched U.S. sample was found. Conclusively, the results indicate that scores on the Norwegian PID-5 have sound psychometric properties, which are substantially comparable with the original U.S. version, supporting its use in a Norwegian population. PMID- 27661477 TI - Study days. PMID- 27661478 TI - Keeping the pressure high on preventionHealth care professionals have long recognised pressure sores as a problem ( 1 , 2 , 3 ). Attention has focused on the monetary cost and scale of the issue ( 4 ) in terms of pain caused and competition for finite resources ( 5 ). The Health of the Nation consultative document ( 6 ) estimated that 6.7 per cent of the adult hospital population are affected, costing the NHS at least L60 million a year. Many consider these sores preventable, and believe the deployment of resources in the health service should focus on prevention instead of treatment ( 7 ). AB - In early 1990, doctors, nurses and health care professionals at St George's Hospital were concerned about the number of patients with pressure sores, but were frustrated by their inability to respond appropriately when problems were identified. A one-day audit at the hospital in March 1990 suggested that 16.8 per cent of patients had a pressure sore and 51 per cent were at risk, as identified by the Waterlow risk assessment tool ( 8 ). Preventive aids and equipment were scarce, and there were no storage, distribution or maintenance systems for the little available. Although there had been negligible investment in equipment, the hospital had spent L127,000 on the rental of pressure relieving devices in 1989/90. PMID- 27661479 TI - Nation is alerted to nurses' work fears. AB - Nurse training numbers fact- being cut by half, Royal College of Nursing General Secretary Christine Hancock warned last week at the first of a national network ofNurses workcampaign launches. PMID- 27661480 TI - Students' course plans hit. AB - Thirty prospective student nurses, due to begin training at St George's and Roehampton College of lealth Studies next month, have been told the course has been cancelled. PMID- 27661481 TI - Reinstatement won by nurse struck off for motor offences. AB - A nurse who was struck off the UKCC register in August 1991 for committing motoring offences won her battle for reinstatement at the Court of Appeal last week. PMID- 27661483 TI - Staff could face random drinking test. AB - Staff who refuse to take a breath test at a Liverpool hospital could face disciplinary action under new proposals. PMID- 27661482 TI - Tough time ahead after Bland ruling. AB - Nurses caring for Tony Bland face an 'extremely difficult' time after the House of Lords confirmed he will be allowed to die, RCN General Secretary Christine Hancock has said. PMID- 27661484 TI - Call for suspension of London bed closures. AB - Labour and the Liberal Democrats have called for a suspension of bed closures in London pending huge investment in primary care services. PMID- 27661486 TI - Talks due on regrading backlog. AB - Proposals to deal with the huge backlog of outstanding clinical grading appeals were due to be discussed at a meeting of nurses' leaders and management yesterday (Tuesday). PMID- 27661485 TI - Report highlights the lack of respite care services. AB - The lack of help for Britain's six-million carers is highlighted in a new report on respite care published jointly by the RCN and the Spastics Society. PMID- 27661487 TI - Shadows cast by redundancy offers. AB - Voluntary redundancy has been offered to nurses at an Oxford hospital because services are being rationalised' and there are uncertainties over contracts for the next financial year. PMID- 27661489 TI - Paediatric recruitment crisis. AB - A hospital in Newcastle may recruit paediatric nurses overseas to fill vacancies caused by national shortages. PMID- 27661488 TI - Call for new budget guidance. AB - Urgent new spending guidelines are being rushed out for health authorities as Whitehall wakes up to the worsening cash crisis in the National Health Service. PMID- 27661491 TI - ? PMID- 27661490 TI - L12m for consultant posts. AB - The government has pledged L12 million in new funding to help reduce junior doctors' hours, most of which will go towards financing new consultant posts. PMID- 27661492 TI - Commons call for national database of vacant posts. AB - Ministers are being urged to create a computerised, national nursing database showing every vacant post in the United Kingdom. PMID- 27661494 TI - 'Resist temptation to become involved in trusts' decisions'. AB - Nurses in purchasing teams must not become involved in Trusts' decisions about how services are organised or managed, senior Scottish nurses heard last week. PMID- 27661493 TI - P2000 information services are poor. AB - An important report has condemned library and information services for students on Project 2000 courses as 'underfunded and inadequate'. PMID- 27661495 TI - Investigation over alleged sabotage. AB - Investigations are under way into an alleged bid to sabotage nurses' evidence to the Health Ombudsman. PMID- 27661496 TI - Survey shows great support for tobacco advertising ban. AB - Three in four of all people and nearly two in three smokers support a total ban on tobacco advertising, according to a Health Education Authority survey published last week. PMID- 27661498 TI - Report highlights risks of rationing health services. AB - Making purchasing health authorities responsible for rationing services is 'spurious and possibly risky', the author of a National Association of Health Authorities and Trusts research paper has warned. PMID- 27661499 TI - Assessing trolley and table products. AB - There is a move towards the adoption of district-wide approaches to pressure sore prevention, with prevention policies incorporating solutions to the problems encountered by services such as ambulance, X-ray, theatre, and A&E ( 1 , 2 , ). PMID- 27661500 TI - Into europe. AB - The real benefit of Europe for Britain lies in escape from an introverted island mentality to a wider, more open society stimulated by closer contact and competition with other people. PMID- 27661501 TI - ? AB - A solution to the problem of patients who slip down their beds lus been found in the form of a bed-foot support. The adjustable support can be attached to the end of the bed, enabling patients to rest their feet against it as well as using it as a means of exercising their legs. The support w ill reduce the time spent by nurses on lifting patients and save possible back injuries, the manufacturers claim. It will also lx- ideal for post-operative and geriatric patients, they say, and w ill reduce the risk of pressure sores by keeping bedclothes off the feet. Further information is available from Paul Drake. BDH Engineering. Tel: 0223 845088. PMID- 27661502 TI - Nurses check shetlanders after oil spill. AB - Nurses on Shetland have been providing health checks for islanders living within three miles of the stricken Braer oil tanker to try to reveal the impact of the disaster. PMID- 27661503 TI - Child services overshadowed by adult needs. AB - Children are not always nursed by appropriately trained staff, even after widely publicised shortages on a Birmingham paediatric unit contributed to the government's decision to reform the health service, RCN General Secretary Christine Hancock said. PMID- 27661505 TI - Alternative review of community mix. AB - A review of community nursing skill mix has been carried out by the community health team in Newcastle. PMID- 27661504 TI - UK 'fails' on children's rights. AB - Britain is failing to meet standards outlined in the United Nations Convention on the rights of the child, leaving children from minority ethnic groups especially vulnerable to inadequate health and social care, a leading children's rights campaigner has said. PMID- 27661507 TI - Research results being ignored. AB - Research showing the benefits of moist wound healing has been ignored by nurses and doctors around the world, delegates at a recent international conference on wound healing and skin physiology in Bochum, Germany, were told. PMID- 27661506 TI - New international wound care group. AB - A multidisciplinary international group devoted to the promotion of positive approaches to wound care has been formed. PMID- 27661508 TI - Ireland. AB - Nurses in Ireland are calling for pay rises of up to 40 per cent, and the first radical change in grading structures for 14 years, World of Irish Nursing reports. PMID- 27661510 TI - Protest in commons over 'gender choice clinics'. AB - The government is considering legislation to control or even outlaw 'gender choice' clinics. PMID- 27661509 TI - United States. AB - The American Nurses' Association has praised President Bill Clinton for lifting a 'gagging order' on nurses working in the country's 4,000 family planning clinics. PMID- 27661511 TI - Hi-tech gobbledegook is alien to 'language' nurses use. AB - Computer experts are inventing a new cybernetic language based on how nurses talk. PMID- 27661513 TI - France. AB - Taxes on cigarettes in France have been increased by 15 per cent, the first of an overall rise of 30 per cent. Part of the revenue raised will help subsidise motor racing which lost its sponsors following a recent national ban on cigarette advertising. The remainder will go to the social security service. PMID- 27661512 TI - Austria. AB - Ninety-two per cent of infant leukaemia patients attending Graz University's innovative Children's Cancer Clinic recover - compared with an international average of 75 per cent. Treatment at the clinic combines conventional leukaemia therapy and bone marrow transplants, and pays special attention to patients' psychological welfare. PMID- 27661514 TI - Suicide patterns reflect social and ethnic origins. AB - Suicide rates among first generation immigrants are broadly the same as in their countries of origin, a government survey of health trends reveals. PMID- 27661515 TI - Pre-op local anaesthetic may relieve post-op pain. AB - Local anaesthetic given before a general anaesthetic may reduce the severity of postoperative pain, it has been argued. PMID- 27661516 TI - Information reduces patient grievances. AB - Patients have a right to receive accurate information about their treatment and the risks involved, a report on a survey of patients in Sheffield has claimed. PMID- 27661518 TI - Parenteral route for hepatitis C spread. AB - Hepatitis C virus (HCV) is more likely to be transmitted parenterally than by heterosexual sex, American researchers say. PMID- 27661517 TI - Infant feeding after acute diarrhoea. AB - Infants under six months with diarrhoea whose only food is milk or formula, should continue full strength feeding as soon as dehydration has been corrected. PMID- 27661519 TI - Changing pattern of gonorrhoea in men? AB - Has the nature of gonorrhoea changed? Researchers from St Thomas's Hospital believe it has. PMID- 27661520 TI - Higher risk of jaundice with flucloxacillin. AB - Older people given flucloxacillin and those prescribed it for longer than two weeks face a substantially greater risk of developing jaundice. PMID- 27661521 TI - Height, albuminuria and cardiovascular disease. AB - Microalbuminuria and short stature in men are associated and both these factors have been associated with cardiovascular risk. Microalbuminuria has a powerful association with macrovascular disease in people with diabetes. To assess any association in non-diabetics, researchers studied a random sample of 1,046 people. PMID- 27661523 TI - Still battling on. AB - It's 75 years ago this week since women were first allowed to vote in the United Kingdom. But in 1918 you could only vote if you were over 30 years of age or owned property. It wasn't until 1928 that women campaigners succeeded in achieving full voting rights. Kathleen Halpin, now in her ninetieth year, was an ardent supporter of women's issues and dedicated her life to the voluntary services, which she asserts played a significant role in their emancipation. Despite her years, she has become increasingly concerned with trying to preserve the things she fought hardest for. PMID- 27661522 TI - Keeping on the right track. AB - In the outpatient department a woman has her worst fears confirmed - she has a lymphoma. That is all the information she is able to take in. She hears nothing of the consultant's optimism about the outcome of treatment. Accompanied by a nursing auxiliary', she returns to her car in a state of considerable shock. Before reaching the car she breaks down. Fortunately for her, she is a patient of the Victoria Hospital in Blackpool and fortunately the nursing auxiliary knows of the presence of Tramline, the hospital support team. The auxiliary makes a phone call and gets one of the team members to support, counsel and provide the woman with a full explanation. PMID- 27661524 TI - Fear at the cutting edge. AB - Midwifery tutor Gina Criss, a Bachelor of Education student at London's South Bank University, forecasts a gloomy time for herself and 26 colleagues on the course. PMID- 27661526 TI - Degree of balance must be achieve. AB - I would like to congratulate those nurses from England Licky enough to have been voted on to the United I Kingdom Central Council. PMID- 27661525 TI - No job for life. AB - Jobs for life in the health service are a thing of the past, and it seems job security may be heading the same way. Like other industries, health care is now part of the market. And the market dictates that when cash is tight, jobs are on the line - nurses' jobs included. Changes in the way health care is organised, with a growing emphasis on developing primary services, also affect the number of staff needed to deliver care. The Tomlinson report has focused all eyes on London, where opinion seems united that change must take place. The question is how it should happen and at what cost to the workforce. But it is not only London that is being 'Tomlinsoned'. Services in Glasgow, Cardiff, Liverpool, Birmingham and Northern Ireland arc also under review and other areas are likely to follow suit. PMID- 27661527 TI - Concern over future of care provision. AB - We are 14 district nursing students concerned about the future of care provision in the community, in view of the implications of the implementation of the Community Care Act in April. PMID- 27661528 TI - Getting over the fear of icebreaking. AB - I found it slightly ironic that, as a gynaecological ward sister, Jill Diaper should say she found the prospect of icebreaking 'a most uncomfortable and embarrassing imposition'. (Letters, January 27). PMID- 27661529 TI - Close the offices and open the wards. AB - The NHS authorities have spent years - and a lot of money - opening offices and closing wards. PMID- 27661530 TI - The legal implications of aromatherapy. AB - As a nurse teacher and aromatherapist I was pleased to discover the RCN/Nursing Standardconferences 'Aromatherapy and Nursing' planned for this year will explore legal issues in addition to the application of aromatherapy in care settings. PMID- 27661531 TI - Not selling nursing down the river. AB - I must comment on Gary Jones' assumption that the chief nurses of Trusts distance themselves from the profession (Letters, January 13). PMID- 27661532 TI - Information exchange. AB - Information exchange exists as part of our commitment to networking and nursing empowerment. If you need to know something the answer should be out there somewhere. Geographical isolation should not entail professional isolation. Address your queries to Information Exchange - and readers, do help enquirers if you can. And let us know if your request leads you to information that would be useful to the wider world of nursing. PMID- 27661533 TI - Answering a poor substitute. AB - * I would like to redress the balance following the biased, negative and emotive account by Barbara Green. PMID- 27661534 TI - ? AB - * The 83-bed home in which I work is one of the larger purpose-built homes in the North East. The staff are especially chosen to work with elderly people and the residents receive excellent care. On most shifts we probably have better staffing levels than hospitals. PMID- 27661535 TI - Answering a poor substitute. AB - Barbara Green's article was not only fictional but disrespectful. It did not do justice to the independent minded, wise and practical people who are typical of the residents I have met during 30 years of caring for elderly people. PMID- 27661536 TI - Good for starters? PMID- 27661538 TI - Stress busters Holden R Stress busters Thorsons 314pp 0-7225-2632-6. AB - Stress is an inevitable part of life. It can be harnessed creatively, but it can also be debilitating. PMID- 27661537 TI - The right to choose Huston P Earthscan Publications 182pp L9.95 1-85383-123-9. AB - Family planning services have developed steadily in England since Marie Stopes's work in the 1920s and 19.30s; today's reproducing generation can take for granted the right to choose parenthood and have access to safe and reliable contraception and medical supervision. PMID- 27661540 TI - Network factfile. PMID- 27661539 TI - The practitioner as teacher The practitioner as teacher Hinchliff S editor Scutari Press 198pp L14.50 1-871364-70-1 [Formula: see text]. AB - Changes in nurse education, coupled with an increased emphasis on the learning needs of both clients and carers require the practising nurse to have sound knowledge and skills in teaching and learning. PMID- 27661541 TI - Career listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain alt relevant details and be posted or faxed to Susan B/oodu'orth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27661542 TI - Status of personal health requirement for graduation at institutions of higher education in the United States. AB - OBJECTIVE: The purpose of this study was to examine the proportion of higher education institutions in the United States that require a personal health course (PHC) for graduation and to describe the nature of such requirements. Participants: This study included a random sample of public and private institutions of higher education (IHE) with undergraduate programs within the United States (N = 310). Data were collected between September 2014 and May 2015. METHODS: University catalogs were accessed from the institutions' public Web sites to determine whether a PHC was offered, and whether it was exclusively or optionally required for graduation. RESULTS: The majority (55.8%) of the sample offered at least 1 PHC, with only 10% exclusively requiring the course and an additional 10% optionally required the course. CONCLUSIONS: Although the utility of undergraduate students completing a PHC is clear, the majority of institutions do not require such a course for degree conferral. PMID- 27661543 TI - [Pulmonary hypertension survival]. PMID- 27661544 TI - [Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary vasodilator therapies]. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy. AIM: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile. PATIENTS AND METHODS: One hundred fifteen patients aged 43 +/- 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 +/- 14 mmHg and their six minutes walking capacity was 368 +/- 119 m. They were followed for 58 +/- 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH. RESULTS: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival. CONCLUSIONS: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature. PMID- 27661545 TI - [Radiation protection provided by tungsten bismuth caps during interventional cardiology]. AB - BACKGROUND: The effectiveness against radiation of tungsten bismuth caps, used in interventional cardiology is not well known. AIM: To determine the degree of radiation protection conferred by these caps in real work conditions. MATERIAL AND METHODS: We compared the gross electric charges received at brain lobe levels by three occupationally exposed professionals who participated in 22 consecutive procedures, inside and outside of the tungsten bismuth cap. RESULTS: The median electric charges outside and inside the cap were 3.71 (range 1.46-5.62) and 2.2 (range 1.29-3.93) nC, which correspond to a 40% radiation attenuation. However, the protection was heterogeneous. CONCLUSIONS: Tungsten bismuth caps provide an adequate attenuation, but its degree is heterogeneous. PMID- 27661547 TI - [Glomerular filtration rate before death, in patients who died with a functioning kidney graft]. AB - BACKGROUND: Death with a functioning kidney graft is now the leading cause of graft loss after renal transplantation. AIM: To determine if renal function at the last outpatient visit before the recipient?s death was different according to the following causes of death: infections, cardiovascular diseases, gastrointestinal disorders or cancer. PATIENTS AND METHODS: Retrospective cooperative cohort study conducted in two kidney transplant centers. All patients who received a kidney graft in the last 32 years were included. During that lapse, 431 kidney transplants were performed. Among them, 85 patients died with a functioning graft and were classified due to their cause of death. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease formula. Declining renal function was defined as a > 20% decline in eGFR during the last 6 months prior to the last outpatient visit. RESULTS: Eighty four patients were included in the analysis. Of these, 28.2% died of cardiovascular causes, 35.3% of infectious diseases, 15.3% of cancer and 20% of digestive diseases. Patients dying from cancer had a significantly higher eGFR prior to death than those who died from cardiovascular causes, infectious and digestive diseases (p < 0.01). Declining renal function occurred in 34.8% of deaths from cardiovascular causes, 39.3% from infectious diseases, 16.7% from cancer and 40% from digestive diseases. There were no significant differences between groups. CONCLUSIONS: Kidney graft recipients who die with a functioning graft have better renal function prior to their death when it is due to cancer than when it originates from infectious, cardiovascular or digestive diseases. Declining renal function is similar in the four groups of death causes. PMID- 27661546 TI - [Effects of a resistance training program in patients with chronic kidney disease on hemodialysis]. AB - BACKGROUND: Exercise may be a therapeutic tool for improving the functional capacity in patients with chronic kidney disease (CKD) who are on hemodialysis (HD). AIM: To determine the effects on muscle strength (MS), functional capacity (FC) and quality of life related to health (QOLRH) of a resistance training program in patients with CKD on HD. PATIENTS AND METHODS: Thirteen CKD patients aged 38.8 +/- 3 years, (7 men) on HD for more than one year participated in an exercise program twice a week during 8 weeks. At the beginning and at the end of the program, MS using a knee extension isometric strength test, FC using the six minutes walking test (6MWT) and QOLRH using the KDQOL CV-36 questionnaire were evaluated. Heart and respiratory rates, blood pressure, oxygen saturation and modified Borg scale were measured as control variables. RESULTS: After training, there were significant improvements in MS in both legs; in the distance travelled during 6MWT and in the physical component summary score of the KDQOL-36. Furthermore, a significant decline in diastolic blood pressure was observed. All other control variables did not change significantly. CONCLUSIONS: Exercise training during eight weeks in CKD patients in HD resulted in significant improvements in muscle strength, walking capacity and in the physical component of a quality of life score for patients with CKD. PMID- 27661548 TI - [Quality assessment of clinical practice guidelines of the Chilean explicit guarantees in healthcare program]. AB - BACKGROUND: High quality practice guidelines are of utmost importance in clinical medicine. AIM: To evaluate the methodological quality of Clinical Practice Guidelines (CPG) for 80 high burden health conditions included in the ?Explicit Guarantees in Healthcare? (EGH) program available on July 2014, elaborated and published by the Ministry of Health of Chile. MATERIAL AND METHODS: A cross sectional observational study using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument to evaluate the methodological quality of the current CPGs for EGH. Two reviewers assessed each CPG independently, obtaining standardized scores according for each dimension included in the AGREE II instrument. RESULTS: Eighty one CPGs were evaluated. They were generally considered of reasonable quality, obtaining high scores in the following domains: Scope and Purpose (81.3%), Clarity of Presentation (78.6%) and Editorial Independence (76.5%). The following domains had a score under 60%: Stakeholder Involvement (51.3%), Rigor of Development (41.4%) and Applicability (33.6%). CONCLUSIONS: The CPGs elaborated for the EGH program have high scores in domains such as the Scope and Purpose, Clarity of Presentation and Editorial Independence. Their scores in other dimensions such as Stakeholder Involvement, Rigor of Development and Applicability can be still improved. PMID- 27661549 TI - [The influence of parental healthy behaviors on healthy lifestyles of early adolescents]. AB - BACKGROUND: Family behavior models may influence health promoting conducts among adolescents. AIM: To determine the association between health promoting behaviors among parents and healthy behaviors of early adolescents. MATERIAL AND METHODS: Analysis of the baseline assessment of a longitudinal study of early adolescents in the city of San Felipe, Region of Valparaiso, Chile. Parents and their teenage children, attending 5th to 7th grade, from ten municipal schools, participated in this study. Self-reported questionnaires were used to assess healthy lifestyles, answered separately by parents and their children. Univariable and multivariable ordinal logistic regression analyses with complete data were carried out, using the students? health promoting behaviors as dependent variables and the same behaviors among parents as the main predictors, controlling for other personal and family variables. RESULTS: We contacted 1,035 parents and 682 consented to participate along with 560 students. The mean age of adolescents was 11.5 +/- 1.2 years (49% females) The mean age of parents was 39.8 +/- 8.8 years and 90% were women. The parental behaviors associated with teenage health promoting behaviors were eating vegetables (odds ratio (OR) = 1.22, p < 0.05), having breakfast (OR = 1.27, p < 0.05), do stretching exercises every day (OR = 1.19, p < 0.05) and take some time for relaxation (OR = 1.24, p < 0.05). CONCLUSIONS: These results show an association between healthy behaviors among parents and these behaviors among their adolescent offspring. PMID- 27661550 TI - [Management of pediatric patients with esophageal varices]. AB - BACKGROUND: There is a paucity of good quality research about the diagnosis of esophageal varices and the prophylaxis and treatment of variceal bleeding in pediatric patients with portal hypertension There is little consensus and practically no evidence-based approach about the management of these patients. AIM: To describe the behavior and preferences of pediatric gastroenterologists in Chile in the management of portal hypertension in children. MATERIAL AND METHODS: An online survey was sent to Chilean pediatric gastroenterologists, with questions evaluating the physicians? approaches to screening of esophageal varices in children with portal hypertension, and their preferred methods of prophylaxis and initial management of variceal bleeding. RESULTS: Thirty five of 69 contacted physicians answered the survey (51%). Twenty nine pediatric gastroenterologists (83%) screen for esophageal varices in patients with clinical evidence of portal hypertension, and 12 (34%) in every patient with chronic liver disease. Twenty eight respondents (80%) use primary prophylaxis, mainly beta blockers. Octreotide, proton pump inhibitors and endoscopy are the most common practices in the initial management of an esophageal varix bleed. The methods mostly used as secondary prophylaxis are band ligation and beta blockers. In the case of recurrent hemorrhage, besides band ligation, management with Transjugular Intrahepatic Portosystemic Shunt (TIPS) and hepatic transplantation are more likely. CONCLUSIONS: Even though most pediatric gastroenterologists in this survey are inclined to offer endoscopic screening of esophageal varices and prophylaxis to patients with portal hypertension, this is not a universal behavior. There are different approaches mainly in the election of secondary prophylaxis and the initial management of variceal bleeding. PMID- 27661551 TI - [Inequality in the prevalence of intestinal parasitic infections among schoolchildren from urban and rural schools]. AB - BACKGROUND: Parasitic infections in children reflect social inequalities throughout the world, especially in urban and rural territories. AIM: To assess inequalities in the prevalence of infections by protozoa and intestinal helminths and associated factors in children of different geographical areas from the commune of Puerto Montt. MATERIAL AND METHODS: Cross-sectional study carried out in 103 students from one urban and two rural schools in the commune of Puerto Montt. A socio-demographic survey was applied and the presence parasitic infections was evaluated in serial stool samples. RESULTS: The prevalence of Protozoan and intestinal helminthic infections were 37.5 and 68.1% in urban and rural areas respectively. A regression analysis showed that the differences between rural and urban children, disappear when the results are adjusted by family income and the quality of sewage disposal. In urban children, the prevalence of parasitic infections increases along with the decrease in family income. CONCLUSIONS: Income and sanitary conditions rather than being or urban or rural origin explain the variations in rates of childhood parasitic infections. Infections with protozoa and intestinal helminths are an indicator of social inequality in health. PMID- 27661552 TI - [Assessment of a brief fatigue inventory in patients with hematologic malignancies]. AB - BACKGROUND: Fatigue is one of the most common and distressing symptoms experienced by cancer patients. AIM: To validate the Brief Fatigue Inventory in people treated for hematological neoplasms. MATERIAL AND METHODS: In a cross sectional study, the Brief Fatigue Inventory was answered by 122 patients aged 40 +/- 14 years (50% women) treated for hematological neoplasms at an intensive hematological unit of a public hospital between July 2010 and July 2013. Socio demographic and clinical parameters were obtained from their clinical records. RESULTS: Fatigue was present in nearly all patients (99.2%) in minor (50%), moderate (36.9%) or severe (12.3%) levels. The average fatigue score was 4.5 +/- 1.9). The Brief Fatigue Inventory had a good internal consistency (Cronbach?s alpha = 0.973) and proved to be one-dimensional (84.3% of the explained variance). Women reported that fatigue interfered more with enjoy-ment of life than men (p = 0.036). CONCLUSIONS: The Brief Fatigue Inventory is a reliable instrument that can be used in clinical practice. It allows a quick assessment of the level of fatigue. People treated for hematologic cancer have a high prevalence of fatigue. PMID- 27661553 TI - [The urgent need for an evaluation system on health interventions]. PMID- 27661554 TI - [A review on thoracic ultrasound]. AB - The use of thoracic ultrasound as a diagnostic tool in the emergency department, intensive care unit or in patients with pulmonary diseases is increasing steadily. It is used to guide percutaneous tracheostomies, to assess pleural effusions, to rule out pneumothorax, and to guide the placement of endovascular and pleural catheters. It is also useful in the assessment of patients with dyspnea. The aim of this review is to provide the practical and technical basics for the use of this diagnostic tool among internists and specialists in pulmonary diseases. PMID- 27661555 TI - [The role of gut microbiota in the regulation of the immune response]. AB - The gastrointestinal tract hosts around 10(14) bacterial microorganisms, in a constantly growing density from the stomach to the distal colon. This microbiota is composed by more than 500 species of bacteria, which are quickly acquired after birth, fairly stable during the host?s life, and essential for human homeostasis. These bacteria have important functions, such as stimulating the immune system, protecting the host from invading bacteria and viruses, and improving digestion, especially of complex carbohydrates. Also, the gut microbiota interacts directly with the immune system. However, the interaction of the intestinal epithelium and its microbiota with the immune system has yet to be fully understood. Secretory immunoglobulin A, produced by the plasma cells in Peyer?s patches and in the lamina propria, maintains non-invasive commensal bacteria and neutralize invasive pathogens. Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity. They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells. Dendritic cells supervise the gut microenvironment too, keeping an immunological equilibrium and tolerance. The importance of the gut microbiota in regulating the immune system lies mostly in the homeostasis-or positive equilibrium. Thus, many diseases are a consequence of poor interactions or a loss of this equilibrium. PMID- 27661556 TI - [The impact of a better coordination between emergency and intensive care units in the care of critically ill patients]. AB - The need for critical care services is increasing in Chile. Critical care beds and specialists in this area are scarce. In this article we discuss some aspects that hamper the care of critically ill patients from their arrival to the emergency department to their transfer to the ICU. Special emphasis is given to system saturation and its multiple causes. The benefits of an integrative approach between emergency medicine and critical care specialists are highlighted and some solutions are proposed to strengthen this partnership. PMID- 27661557 TI - [Mental health in Chile and Finland: Challenges and lessons]. AB - This article analyses and compares the epidemiology of mental disorders and relevant public policies in Chile and Finland. In Chile, a specific mental health law is still lacking. While both countries highlight the role of primary care, Finland places more emphasis on participation and recovery of service users. Comprehensive mental health policies from Finland, such as a successful suicide prevention program, are presented. Both countries have similar prevalence of mental disorders, high alcohol consumption and high suicide rates. In Chile, the percentage of total disease burden due to psychiatric disorders is 13% and in Finland 14%. However, the resources to address these issues are very different. Finland spends 4.5% of its health budget on mental health, while in Chile the percentage is 2.2%. This results in differences in human resources and service provision. Finland has five times more psychiatric outpatient visits, four times more psychiatrists, triple antidepressant use and twice more clinical guidelines for different psychiatric conditions. In conclusion, both countries have similar challenges but differing realities. This may help to identify gaps and potential solutions for public health challenges in Chile. Finland?s experience demonstrates the importance of political will and long-term vision in the construction of mental health policies. PMID- 27661558 TI - [Cushing syndrome in a HIV patient using inhaled steroids. Report of one case]. AB - We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months. PMID- 27661559 TI - [Giant coronary artery fistula: Report of one case]. AB - Coronary artery fistulae are abnormal connections between a coronary artery and any cardiac chamber or other vessels. Most of them have a congenital origin. We report a 60 years old woman referring a history of progressive dyspnea and orthopnea during the last year. A continuous heart murmur was audible in the third and fourth intercostal spaces at the left sternal border. Electrocardiogram was normal and echocardiography showed mild dilation of right cavities and an image suggesting a dilated right coronary artery with flow to right atrium. Coronary angiography was performed, showing a normal left coronary artery and a very large, tortuous right coronary artery with an extensive communication to coronary venous sinus. Surgical treatment was decided and was performed without incidents. The patient is well after five years of follow up. PMID- 27661560 TI - [Medical liability: the dilemma between civil and criminal justice]. PMID- 27661561 TI - [Headache seasonality in the Northern and Southern hemispheres: an approach using Google Trends]. PMID- 27661562 TI - Randomized controlled trials for degenerative lumbar spondylolisthesis: which patients benefit from lumbar fusion? PMID- 27661563 TI - An assessment of data and methodology of online surgeon scorecards. AB - OBJECTIVE Recently, 2 surgeon rating websites (Consumers' Checkbook and ProPublica) were published to allow the public to compare surgeons through identifying surgeon volume and complication rates. Among neurosurgeons and orthopedic surgeons, only cervical and lumbar spine, hip, and knee procedures were included in this assessment. METHODS The authors examined the methodology of each website to assess potential sources of inaccuracy. Each online tool was queried for reports on neurosurgeons specializing in spine surgery and orthopedic surgeons specializing in spine, hip, or knee surgery. Surgeons were chosen from top-ranked hospitals in the US, as recorded by a national consumer publication ranking system, within the fields of neurosurgery and orthopedic surgery. The results were compared for accuracy and surgeon representation, and the results of the 2 websites were also compared. RESULTS The methodology of each site was found to have opportunities for bias and limited risk adjustment. The end points assessed by each site were actually not complications, but proxies of complication occurrence. A search of 510 surgeons (401 orthopedic surgeons [79%] and 109 neurosurgeons [21%]) showed that only 28% and 56% of surgeons had data represented on Consumers' Checkbook and ProPublica, respectively. There was a significantly higher chance of finding surgeon data on ProPublica (p < 0.001). Of the surgeons from top-ranked programs with data available, 17% were quoted to have high complication rates, 13% with lower volume than other surgeons, and 79% had a 3-star out of 5-star rating. There was no significant correlation found between the number of stars a surgeon received on Consumers' Checkbook and his or her adjusted complication rate on ProPublica. CONCLUSIONS Both the Consumers' Checkbook and ProPublica websites have significant methodological issues. Neither site assessed complication occurrence, but rather readmissions or prolonged length of stay. Risk adjustment was limited or nonexistent. A substantial number of neurosurgeons and orthopedic surgeons from top-ranked hospitals have no ratings on either site, or have data that suggests they are low-volume surgeons or have higher complication rates. Consumers' Checkbook and ProPublica produced different results with little correlation between the 2 websites in how surgeons were graded. Given the significant methodological issues, incomplete data, and lack of appropriate risk stratification of patients, the featured websites may provide erroneous information to the public. PMID- 27661564 TI - Anatomical differences in patients with lumbosacral transitional vertebrae and implications for minimally invasive spine surgery. AB - OBJECTIVE The objective of this study was to investigate the neurovascular and anatomical differences in patients with lumbosacral transitional vertebrae (LSTV) and the associated risk of neurovascular injury in minimally invasive spine surgery. METHODS The authors performed a retrospective study of CT and MR images of the lumbar spine obtained at their institution between 2010 and 2014. The following characteristics were evaluated: level of the iliac crest in relation to the L4-5 disc space, union level of the iliac veins and arteries in relation to the L4-5 disc space, distribution of the iliac veins and inferior vena cava according to the different Moro zones (A, I, II, III, IV, P) at the L4-5 disc space, and the location of the psoas muscle at the L4-5 disc space. The findings were compared with findings on images obtained in 28 age- and sex-matched patients without LSTV who underwent imaging studies during the same time period. RESULTS Twenty-eight patients (12 male, 16 female) with LSTV and the required imaging studies were identified; 28 age- and sex-matched patients who had undergone CT and MRI studies of the thoracic and lumbar spine imaging but did not have LSTV were selected for comparison (control group). The mean ages of the patients in the LSTV group and the control group were 52 and 49 years, respectively. The iliac crest was located at a mean distance of 12 mm above the L4-5 disc space in the LSTV group and 4 mm below the L4-5 disc space in the controls. The iliac vein union was located at a mean distance of 8 mm above the L4-5 disc space in the LSTV group and 2.7 mm below the L4-5 disc space in the controls. The iliac artery bifurcation was located at a mean distance of 23 mm above the L4-5 disc space in the LSTV group and 11 mm below the L4-5 disc space in controls. In patients with LSTV, the distribution of iliac vein locations was as follows: Zone A, 7.1%; Zone I only, 78.6%; Zone I encroaching into Zone II, 7.1%; and Zone II only, 7.1%. In the control group, the distribution was as follows: Zone A only, 17.9%; Zone A encroaching into Zone I, 75%; and Zone I only, 7.1%. There were no iliac vessels in Zone II in the control group. The psoas muscle was found to be rising away laterally and anteriorly from the vertebral body more often in patients with LSTV, resulting in the iliac veins being found in the "safe zone" only 14% of the time, greatly increasing the risk of vascular injury. CONCLUSIONS In patients with LSTV, the iliac crest is more likely to be above the L4-5 disc space, which increases the technical challenges of a lateral approach. The location of the psoas muscle rising away laterally and ventrally in patients with LSTV compared with controls and with the union of the iliac veins occurring more often above the L4-5 disc space increases the risk for iatrogenic vascular injury at the L4-5 level in this patient population. PMID- 27661565 TI - Magnetization reversal in mixed ferrite-chromite perovskites with non magnetic cation on the A-site. AB - In this work, we have performed Monte Carlo simulations in a classical model for RFe1-x Cr x O3 with R = Y and Lu, comparing the numerical simulations with experiments and mean field calculations. In the analyzed compounds, the antisymmetric exchange or Dzyaloshinskii-Moriya (DM) interaction induced a weak ferromagnetism due to a canting of the antiferromagnetically ordered spins. This model is able to reproduce the magnetization reversal (MR) observed experimentally in a field cooling process for intermediate x values and the dependence with x of the critical temperatures. We also analyzed the conditions for the existence of MR in terms of the strength of DM interactions between Fe(3+) and Cr(3+) ions with the x values variations. PMID- 27661566 TI - Secreted Frizzled-Related Protein 2 and Inflammation-Induced Skeletal Muscle Atrophy. AB - OBJECTIVE: In sepsis, the disease course of critically ill patients is often complicated by muscle failure leading to ICU-acquired weakness. The myokine transforming growth factor-beta1 increases during inflammation and mediates muscle atrophy in vivo. We observed that the transforming growth factor-beta1 inhibitor, secreted frizzled-related protein 2, was down-regulated in skeletal muscle of ICU-acquired weakness patients. We hypothesized that secreted frizzled related protein 2 reduction enhances transforming growth factor-beta1-mediated effects and investigated the interrelationship between transforming growth factor beta1 and secreted frizzled-related protein 2 in inflammation-induced atrophy. DESIGN: Observational study and prospective animal trial. SETTING: Two ICUs and research laboratory. PATIENTS/SUBJECTS: Twenty-six critically ill patients with Sequential Organ Failure Assessment scores greater than or equal to 8 underwent a skeletal muscle biopsy from the vastus lateralis at median day 5 in ICU. Four patients undergoing elective orthopedic surgery served as controls. To search for signaling pathways enriched in muscle of ICU-acquired weakness patients, a gene set enrichment analysis of our recently published gene expression profiles was performed. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to analyze secreted frizzled-related protein 2 expression and protein content. A mouse model of inflammation-induced skeletal muscle atrophy due to polymicrobial sepsis and cultured myocytes were used for mechanistic analyses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gene set enrichment analysis uncovered transforming growth factor-beta1 signaling activation in vastus lateralis from ICU-acquired weakness patients. Muscular secreted frizzled-related protein 2 expression was reduced after 5 days in ICU. Likewise, muscular secreted frizzled-related protein 2 expression was decreased early and continuously in mice with inflammation-induced atrophy. In muscle, secreted frizzled-related protein 2 was predominantly contained in fast twitch/type II myofibers. Secreted frizzled-related protein 2 physically interacted and colocalized with transforming growth factor-beta1 through its cysteine-rich domain. Finally, secreted frizzled-related protein 2 prevented transforming growth factor-beta1-induced atrophy in C2C12 myotubes. CONCLUSIONS: Muscular secreted frizzled-related protein 2 is down-regulated in ICU-acquired weakness patients and mice with inflammation-induced muscle atrophy. Decreased secreted frizzled-related protein 2 possibly establishes a positive feedback loop enhancing transforming growth factor-beta1-mediated atrophic effects in inflammation-induced atrophy. PMID- 27661567 TI - Correction to Determining Chiral Configuration of Diamines via Contact Angle Measurements on Enantioselective Alanine-Appended Benzene-Tricarboxamide Gelators. PMID- 27661568 TI - Monochromatic measurements of the JPSS-1 VIIRS polarization sensitivity. AB - Polarization sensitivity is a critical property that must be characterized for spaceborne remote sensing instruments designed to measure reflected solar radiation. Broadband testing of the first Joint Polar-orbiting Satellite System (JPSS-1) Visible Infrared Imaging Radiometer Suite (VIIRS) showed unexpectedly large polarization sensitivities for the bluest bands on VIIRS (centered between 400 and 600 nm). Subsequent ray trace modeling indicated that large diattenuation on the edges of the bandpass for these spectral bands was the driver behind these large sensitivities. Additional testing using the National Institute of Standards and Technology's Traveling Spectral Irradiance and Radiance Responsivity Calibrations Using Uniform Sources was added to the test program to verify and enhance the model. The testing was limited in scope to two spectral bands at two scan angles; nonetheless, this additional testing provided valuable insight into the polarization sensitivity. Analysis has shown that the derived diattenuation agreed with the broadband measurements to within an absolute difference of about 0.4% and that the ray trace model reproduced the general features of the measured data. Additionally, by deriving the spectral responsivity, the linear diattenuation is shown to be explicitly dependent on the changes in bandwidth with polarization state. PMID- 27661569 TI - Radiation hardening of sol gel-derived silica fiber preforms through fictive temperature reduction. AB - The impact of fictive temperature (Tf) on the evolution of point defects and optical attenuation in non-doped and Er3+-doped sol-gel silica glasses was studied and compared to Suprasil F300 and Infrasil 301 glasses before and after gamma-irradiation. To this aim, sol-gel optical fiber preforms have been fabricated by the densification of erbium salt-soaked nanoporous silica xerogels through the polymeric sol-gel technique. These gamma-irradiated fiber preforms have been characterized by FTIR, UV-vis-NIR absorption spectroscopy, electron paramagnetic resonance, and photoluminescence measurements. We showed that a decrease in the glass fictive temperature leads to a decrease in the glass disorder and strained bonds. This mainly results in a lower defect generation rate and thus less radiation-induced attenuation in the UV-vis range. Furthermore, it was found that gamma-radiation "hardness" is higher in Er3+-doped sol-gel silica compared to un-doped sol-gel silica and standard synthetic silica glasses. The present work demonstrates an effective strategy to improve the radiation resistance of optical fiber preforms and glasses through glass fictive temperature reduction. PMID- 27661570 TI - Intensity fluctuations of asymmetrical optical beams in anisotropic turbulence. AB - Intensity fluctuations of asymmetrical optical beams are examined when such beams propagate through anisotropic turbulence. Anisotropic turbulence is modeled by non-Kolmogorov von Karman spectrum. The variations of the scintillation index are observed against the changes in the asymmetry factor of the Gaussian beam, power law exponent of non-Kolmogorov spectrum, anisotropic factors in the transverse direction, and the link length. It is found that for all the conditions, asymmetry in the optical beam is a disadvantage but the anisotropy in the atmosphere is an advantage for reducing the intensity fluctuations in an optical wireless communications link operating in the atmosphere. PMID- 27661571 TI - GPU acceleration of Monte Carlo simulations for polarized photon scattering in anisotropic turbid media. AB - In earlier studies, we developed scattering models and the corresponding CPU based Monte Carlo simulation programs to study the behavior of polarized photons as they propagate through complex biological tissues. Studying the simulation results in high degrees of freedom that created a demand for massive simulation tasks. In this paper, we report a parallel implementation of the simulation program based on the compute unified device architecture running on a graphics processing unit (GPU). Different schemes for sphere-only simulations and sphere cylinder mixture simulations were developed. Diverse optimizing methods were employed to achieve the best acceleration. The final-version GPU program is hundreds of times faster than the CPU version. Dependence of the performance on input parameters and precision were also studied. It is shown that using single precision in the GPU simulations results in very limited losses in accuracy. Consumer-level graphics cards, even those in laptop computers, are more cost effective than scientific graphics cards for single-precision computation. PMID- 27661572 TI - Close-range photogrammetry with light field camera: from disparity map to absolute distance. AB - A new approach to measure the 3D profile of a texture object is proposed utilizing light field imaging, in which three key steps are required: a disparity map is first obtained by detecting the slopes in the epipolar plane image with the multilabel technique; the intrinsic parameters of the light field camera are then extracted by camera calibration; at last, the relationship between disparity values and real distances is built up by depth calibration. In the last step, a linear calibration method is proposed to achieve accurate results. Furthermore, the depth error is also investigated and compensated for by reusing the checkerboard pattern. The experimental results are in good agreement with the 3D models, and also indicate that the light field imaging is a promising 3D measurement technique. PMID- 27661573 TI - Method for predicting junction temperature distribution in a high-power laser diode bar. AB - A hybrid experimental/numerical method is proposed for predicting the junction temperature distribution in a high-power laser diode (LD) bar with multiple emitters. A commercial water-cooled LD bar with multiple emitters is used to illustrate and validate the proposed method. A unique experimental setup is developed and implemented first to measure the average junction temperatures of the LD bar emitters. After measuring the heat dissipation of the LD bar, the effective heat transfer coefficient of the cooling system is determined inversely from the numerical simulation using the measured average junction temperature and the heat dissipation. The characterized heat dissipation and effective heat transfer coefficient are used to predict the junction temperature distribution over the LD bar numerically under high operating currents. The results are presented in conjunction with the wall-plug efficiency and the center wavelength shift. PMID- 27661574 TI - Design considerations of high-performance InGaAs/InP single-photon avalanche diodes for quantum key distribution. AB - InGaAs/InP single-photon avalanche diodes (SPADs) are widely used in practical applications requiring near-infrared photon counting such as quantum key distribution (QKD). Photon detection efficiency and dark count rate are the intrinsic parameters of InGaAs/InP SPADs, due to the fact that their performances cannot be improved using different quenching electronics given the same operation conditions. After modeling these parameters and developing a simulation platform for InGaAs/InP SPADs, we investigate the semiconductor structure design and optimization. The parameters of photon detection efficiency and dark count rate highly depend on the variables of absorption layer thickness, multiplication layer thickness, excess bias voltage, and temperature. By evaluating the decoy state QKD performance, the variables for SPAD design and operation can be globally optimized. Such optimization from the perspective of specific applications can provide an effective approach to design high-performance InGaAs/InP SPADs. PMID- 27661575 TI - Off-axis digital holographic particle positioning based on polarization-sensitive wavefront curvature estimation. AB - Poor axial resolution in holographic particle imaging applications makes particle positioning in 3D space more complex since the positions are not directly obtained. In this paper we estimate the axial position of micrometer particles by finding the location where the wavefront curvature from the scattered light becomes zero. By recording scattered light at 90 degrees using off-axis holography, the complex amplitude of the light is obtained. By reconstruction of the imaged scene, a complex valued volume is produced. From this volume, phase gradients are calculated for each particle and used to estimate the wavefront curvature. From simulations it is found that the wavefront curvature became zero at the true axial position of the particle. We applied this metric to track an axial translation experimentally using a telecentric off-axis holographic imaging system with a lateral magnification of M=1.33. A silicon cube with molded particles inside was used as sample. Holographic recordings are performed both before and after a 100 MUm axial translation. From the estimated positions, it was found that the mean displacement of particles between recordings was 105.0 MUm with a standard deviation of 25.3 MUm. PMID- 27661576 TI - Disparity between online and offline tests in accelerated aging tests of LED lamps under electric stress. AB - The accelerated aging tests under electric stress for one type of LED lamp are conducted, and the differences between online and offline tests of the degradation of luminous flux are studied in this paper. The transformation of the two test modes is achieved with an adjustable AC voltage stabilized power source. Experimental results show that the exponential fitting of the luminous flux degradation in online tests possesses a higher fitting degree for most lamps, and the degradation rate of the luminous flux by online tests is always lower than that by offline tests. Bayes estimation and Weibull distribution are used to calculate the failure probabilities under the accelerated voltages, and then the reliability of the lamps under rated voltage of 220 V is estimated by use of the inverse power law model. Results show that the relative error of the lifetime estimation by offline tests increases as the failure probability decreases, and it cannot be neglected when the failure probability is less than 1%. The relative errors of lifetime estimation are 7.9%, 5.8%, 4.2%, and 3.5%, at the failure probabilities of 0.1%, 1%, 5%, and 10%, respectively. PMID- 27661577 TI - Multiwavelength laser designed for single-frame digital holography. AB - In this paper, we present a tailored multiwavelength Yb-fiber laser source in the 1.03 MUm spectral region for spatially multiplexed digital holographic acquisitions. The wavelengths with bandwidths below 0.1 nm were spectrally separated by approximately 1 nm by employing fiber Bragg gratings for spectral control. As a proof of concept, the shape of a cylindrically shaped object with a diameter of 48 mm was measured. The holographic acquisition was performed in single-shot dual-wavelength mode with a synthetic wavelength of 1.1 mm, and the accuracy was estimated to be 3% of the synthetic wavelength. PMID- 27661578 TI - Off-axis holographic lens spectrum-splitting photovoltaic system for direct and diffuse solar energy conversion. AB - This paper describes a high-efficiency, spectrum-splitting photovoltaic module that uses an off-axis volume holographic lens to focus and disperse incident solar illumination to a rectangular shaped high-bandgap indium gallium phosphide cell surrounded by strips of silicon cells. The holographic lens design allows efficient collection of both direct and diffuse illumination to maximize energy yield. We modeled the volume diffraction characteristics using rigorous coupled wave analysis, and simulated system performance using nonsequential ray tracing and PV cell data from the literature. Under AM 1.5 illumination conditions the simulated module obtained a 30.6% conversion efficiency. This efficiency is a 19.7% relative improvement compared to the more efficient cell in the system (silicon). The module was also simulated under a typical meteorological year of direct and diffuse irradiance in Tucson, Arizona, and Seattle, Washington. Compared to a flat panel silicon module, the holographic spectrum splitting module obtained a relative improvement in energy yield of 17.1% in Tucson and 14.0% in Seattle. An experimental proof-of-concept volume holographic lens was also fabricated in dichromated gelatin to verify the main characteristics of the system. The lens obtained an average first-order diffraction efficiency of 85.4% across the aperture at 532 nm. PMID- 27661579 TI - Modular pump head design of diffused, metal, and hybrid pump geometry for diode side-pumped high power Nd:YAG laser. AB - In this paper, we present a comparative study on pump heads for a high power diode-side-pumped Nd:YAG laser. The pump head is a modular type, which is in the form of discs, with each disc holding three pump diodes kept at 120 degrees with respect to each other. Unabsorbed pump light from the active medium is reflected by reflectors mounted adjacent to the pump diodes. The performance of a high power pump head made of modular discs mounted with specular or diffused type reflectors was studied. Hybrid pump geometry was also investigated, where the pump head is made up of discs loaded with metal and diffused reflectors, alternately. The discs are loaded around the active medium in such a way that successive discs are rotated by sixty degrees with respect to each other. Fluorescence profiles, thermal lensing, laser output power, and M2 values were studied for pump heads made up of metal, diffused, and hybrid type reflectors. All of the pump heads were studied for three different resonator lengths to maximize the output power with the best beam quality. The experimental results show that the diffused reflector-based geometry in a sixty degree rotated configuration produced the maximum output power and best beam quality in terms of the M2 value. PMID- 27661580 TI - Temporal characterization of petawatt class laser at Shen Guang II facility. AB - Temporal characterization is important to diagnose and measure a petawatt (PW) class laser. We obtained the V curve of the pulse width versus the grating position using pulse width measurement with a mirror image configuration. The temporal range for pulse width was 18 ps with a resolution of 0.05 ps. We measured the pulse contrast between the -60 ps and -6 ps PW class laser within a single shot in the Shen Guang II facility. We measured the pulse contrast between the -91 ps and -60 ps PW class laser after expanding the temporal range. The temporal range was 70 ps, with a dynamic range of eight orders of magnitude. PMID- 27661581 TI - Robustness of a coherence vortex. AB - We study, experimentally and theoretically, the behavior of a coherence vortex after its transmission through obstacles. Notably, we find that such a vortex survives and preserves its effective topological charge. Despite suffering changes on the modulus of the coherence function, these changes disappear during propagation. PMID- 27661582 TI - Compact silicon photonic interleaver based on a self-coupled optical waveguide. AB - We propose and experimentally demonstrate a new scheme to realize an on-chip silicon photonic interleaver by using a self-coupled optical waveguide (SCOW). Benefiting from the high-order filtering property of a multistage SCOW resonator, the device has a smaller footprint and higher extinction ratio compared to conventional ring-assisted Mach-Zehnder interferometer interleavers. Its high fabrication tolerance is also demonstrated in this paper. The operation principle of the proposed interleaver is theoretically analyzed. The designed device is fabricated on a silicon-on-insulator wafer under standard complementary metal oxide semiconductor compatible fabrication processes. Experimental results show that 20 dB extinction ratio and about 8 dB insertion loss can be achieved in the entire C-band without any thermo-optic tuning, verifying the effectiveness of the proposed device as an on-chip interleaver with a compact footprint and high extinction ratio. PMID- 27661583 TI - Efficient patch-based approach for compressive depth imaging. AB - We present efficient camera hardware and algorithms to capture images with extended depth of field. The camera moves its focal plane via a liquid lens and modulates the scene at different focal planes by shifting a fixed binary mask, with synchronization achieved by using the same triangular wave to control the focal plane and the pizeoelectronic translator that shifts the mask. Efficient algorithms are developed to reconstruct the all-in-focus image and the depth map from a single coded exposure, and various sparsity priors are investigated to enhance the reconstruction, including group sparsity, tree structure, and dictionary learning. The algorithms naturally admit a parallel computational structure due to the independent patch-level operations. Experimental results on both simulation and real datasets demonstrate the efficacy of the new hardware and the inversion algorithms. PMID- 27661584 TI - Hybrid algorithm for phase retrieval from a single spatial carrier fringe pattern. AB - A hybrid algorithm is proposed in this study for demodulating a single spatial carrier fringe pattern (FP) of interferometric measurement, which essentially combines the spatial carrier phase shift (SCPS) method and Fourier transform (FT) method. It firstly extracts three phase-shifted FPs from a single spatial carrier FP, then employs the FT method and a subtraction operation to determine the phase shift of three phase-shifted FPs, and finally retrieves the phase map using a least-square phase shift algorithm. The subtraction operation could considerably mitigate the inherent edge error of the FT method, resulting in an increase of accuracy compared with the FT method. It also does not require the background and modulation amplitude of the spatial carrier FP to be constant; thus it is robust and quite suitable for engineering. The factors that may influence the performance of the proposed algorithm are analyzed, including the random and speckle noise, carrier frequency, shape of the background, and modulation amplitude. The feasibility of the proposed algorithm is validated by two experiments, comparing them with the temporal phase-shifted method. The proposed algorithm is expected to be used in interferometric measurement under adverse environments. PMID- 27661585 TI - Detection and counting of a submicrometer particle in liquid flow by self-mixing microchip Yb:YAG laser velocimetry. AB - We observed intermittent modulation by scattered light from a single submicrometer particle moving in the flow channel using a self-mixing microchip Yb:YAG laser Doppler velocimeter (LDV) under lateral beam access. The Doppler shift frequency chirping (i.e., velocity change) was identified in accordance with a particle passage through the beam focus. Single particle counting, which obeys the Poisson distribution, was performed successfully over a long period of time. The experimental results have been reproduced by a numerical simulation. The LDV signal was increased over 20 dB for a 202-nm particle without chirping by collinear beam access with the laser beam axis aligned along the flow direction. PMID- 27661586 TI - From image pair to a computer generated hologram for a real-world scene. AB - We propose an approach to produce computer generated holograms (CGHs) from image pairs of a real-world scene. The ratio of the three-dimensional (3D) physical size of the object is computed from the image pair to provide the correct depth cue. A multilayer wavefront recording plane method completed with a two-stage occlusion culling process is carried out for wave propagation. Multiple holograms can be generated by propagating the wave toward the desired angles, to cover the circular views that are wider than the viewing angle restricted by the wavelength and pitch size of a single hologram. The impact of the imperfect depth information extracted from the image pair on CGH is examined. The approach is evaluated extensively on image pairs of real-world 3D scenes, and the results demonstrate that the circular-view CGH can be produced from a pair of stereo images using the proposed approach. PMID- 27661587 TI - Impact of nonzero boresight pointing errors on the performance of a relay assisted free-space optical communication system over exponentiated Weibull fading channels. AB - The impact of nonzero boresight pointing errors on the system performance of decode-and-forward protocol-based multihop parallel optical wireless communication systems is studied. For the aggregated fading channel, the atmospheric turbulence is simulated by an exponentiated Weibull model, and pointing errors are described by one recently proposed statistical model including both boresight and jitter. The binary phase-shift keying subcarrier intensity modulation-based analytical average bit error rate (ABER) and outage probability expressions are achieved for a nonidentically and independently distributed system. The ABER and outage probability are then analyzed with different turbulence strengths, receiving aperture sizes, structure parameters (P and Q), jitter variances, and boresight displacements. The results show that aperture averaging offers almost the same system performance improvement with boresight included or not, despite the values of P and Q. The performance enhancement owing to the increase of cooperative path (P) is more evident with nonzero boresight than that with zero boresight (jitter only), whereas the performance deterioration because of the increasing hops (Q) with nonzero boresight is almost the same as that with zero boresight. Monte Carlo simulation is offered to verify the validity of ABER and outage probability expressions. PMID- 27661588 TI - Robust infrared small target detection via non-negativity constraint-based sparse representation. AB - Infrared (IR) small target detection is one of the vital techniques in many military applications, including IR remote sensing, early warning, and IR precise guidance. Over-complete dictionary based sparse representation is an effective image representation method that can capture geometrical features of IR small targets by the redundancy of the dictionary. In this paper, we concentrate on solving the problem of robust infrared small target detection under various scenes via sparse representation theory. First, a frequency saliency detection based preprocessing is developed to extract suspected regions that may possibly contain the target so that the subsequent computing load is reduced. Second, a target over-complete dictionary is constructed by a varietal two-dimensional Gaussian model with an extent feature constraint and a background term. Third, a sparse representation model with a non-negativity constraint is proposed for the suspected regions to calculate the corresponding coefficient vectors. Fourth, the detection problem is skillfully converted to an l1-regularized optimization through an accelerated proximal gradient (APG) method. Finally, based on the distinct sparsity difference, an evaluation index called sparse rate (SR) is presented to extract the real target by an adaptive segmentation directly. Large numbers of experiments demonstrate both the effectiveness and robustness of this method. PMID- 27661589 TI - Stripe-shaped apertures in confocal microscopy. AB - We have theoretically verified that, compared with the aperture shapes of previous research, combining two stripe-shaped apertures in a confocal microscope with a finite-sized pinhole improves the axial resolution to a certain extent. Because different stripe shapes cause different effects, we also investigated the relationships among resolution, shapes, pinhole size, and the signal-to background ratio. PMID- 27661590 TI - Measurement of the intermodal crosstalk of a bent multimode waveguide. AB - We quantitatively investigate the main source of the intermodal crosstalk of a silicon-based bent multimode waveguide by experiment. The measurement is performed through time-domain scanning low-coherence interferometry. From the measurement results, one can not only calculate the modal crosstalk, but can also locate the position where the crosstalk appears. The results indicate that the modal mismatch at the points where the curvature of the waveguide changes is the main origin of the modal crosstalk. For a two-mode waveguide with a bending radius of 5 MUm at 1310 nm, the crosstalk is as high as -20 and -16 dB for the fundamental and first-order mode, respectively. This work gives us a deep insight into how the guided modes actually propagate through the bent waveguide. PMID- 27661591 TI - Simple transfer calibration method for a Cimel Sun-Moon photometer: calculating lunar calibration coefficients from Sun calibration constants. AB - The Cimel new technologies allow both daytime and nighttime aerosol optical depth (AOD) measurements. Although the daytime AOD calibration protocols are well established, accurate and simple nighttime calibration is still a challenging task. Standard lunar-Langley and intercomparison calibration methods both require specific conditions in terms of atmospheric stability and site condition. Additionally, the lunar irradiance model also has some known limits on its uncertainty. This paper presents a simple calibration method that transfers the direct-Sun calibration constant, V0,Sun, to the lunar irradiance calibration coefficient, CMoon. Our approach is a pure calculation method, independent of site limits, e.g., Moon phase. The method is also not affected by the lunar irradiance model limitations, which is the largest error source of traditional calibration methods. Besides, this new transfer calibration approach is easy to use in the field since CMoon can be obtained directly once V0,Sun is known. Error analysis suggests that the average uncertainty of CMoon over the 440-1640 nm bands obtained with the transfer method is 2.4%-2.8%, depending on the V0,Sun approach (Langley or intercomparison), which is comparable with that of lunar-Langley approach, theoretically. In this paper, the Sun-Moon transfer and the Langley methods are compared based on site measurements in Beijing, and the day-night measurement continuity and performance are analyzed. PMID- 27661592 TI - Compact fiber optic dual-detection confocal displacement sensor. AB - We propose a dual-detection confocal displacement sensor (DDCDS) with a compact fiber-based optical probe. This all-fiber-optic sensor probe is simple and robust, since it only requires simple alignment of a gradient refractive index lens and a double-clad fiber (DCF). The DDCDS is composed of two point detectors, one coupled to a single mode fiber and the other coupled to a multimode fiber, which are used to measure the light intensity from a core and an inner clad of a DCF, respectively. The ratio of the axial response curves, measured by the two detectors, can be used to obtain a linear relationship between the axial position of the object plane and the ratio of the intensity signals. We demonstrate the performance of the proposed method by measuring micromovement and fast vibration. PMID- 27661593 TI - Design quadrilateral apertures in binary computer-generated holograms of large space bandwidth product. AB - A new approach for designing the binary computer-generated hologram (CGH) of a very large number of pixels is proposed. Diffraction of the CGH apertures is computed by the analytical Abbe transform and by considering the aperture edges as the basic diffracting elements. The computation cost is independent of the CGH size. The arbitrary-shaped polygonal apertures in the CGH consist of quadrilateral apertures, which are designed by assigning the binary phases using the parallel genetic algorithm with a local search, followed by optimizing the locations of the co-vertices with a direct search. The design results in high performance with low image reconstruction error. PMID- 27661594 TI - Suomi National Polar-Orbiting Partnership Visible Infrared Imaging Radiometer Suite polarization sensitivity analysis. AB - The Visible Infrared Imaging Radiometer Suite (VIIRS) is one of five instruments onboard the Suomi National Polar-Orbiting Partnership (SNPP) satellite that launched from Vandenberg Air Force Base, California, on October 28, 2011. It is a whiskbroom radiometer that provides +/-56.28 degrees scans of the Earth view. It has 22 bands, among which 14 are reflective solar bands (RSBs). The RSBs cover a wavelength range from 410 to 2250 nm. The RSBs of a remote sensor are usually sensitive to the polarization of incident light. For VIIRS, it is specified that the polarization factor should be smaller than 3% for 410 and 862 nm bands and 2.5% for other RSBs for the scan angle within +/-45 degrees . Several polarization sensitivity tests were performed prelaunch for SNPP VIIRS. The first few tests either had large uncertainty or were less reliable, while the last one was believed to provide the more accurate information about the polarization property of the instrument. In this paper, the measured data in the last polarization sensitivity test are analyzed, and the polarization factors and phase angles are derived from the measurements for all the RSBs. The derived polarization factors and phase angles are band, detector, and scan angle dependent. For near-infrared bands, they also depend on the half-angle mirror side. Nevertheless, the derived polarization factors are all within the specification, although the strong detector dependence of the polarization parameters was not expected. Compared to the Moderate Resolution Imaging Spectroradiometer on both Aqua and Terra satellites, the polarization effect on VIIRS RSB is much smaller. PMID- 27661596 TI - Comparative analysis of autofocus functions in digital in-line phase-shifting holography. AB - Numerical reconstruction of digital holograms relies on a precise knowledge of the original object position. However, there are a number of relevant applications where this parameter is not known in advance and an efficient autofocusing method is required. This paper addresses the problem of finding optimal focusing methods for use in reconstruction of digital holograms of macroscopic amplitude and phase objects, using digital in-line phase-shifting holography in transmission mode. Fifteen autofocus measures, including spatial-, spectral-, and sparsity-based methods, were evaluated for both synthetic and experimental holograms. The Fresnel transform and the angular spectrum reconstruction methods were compared. Evaluation criteria included unimodality, accuracy, resolution, and computational cost. Autofocusing under angular spectrum propagation tends to perform better with respect to accuracy and unimodality criteria. Phase objects are, generally, more difficult to focus than amplitude objects. The normalized variance, the standard correlation, and the Tenenbaum gradient are the most reliable spatial-based metrics, combining computational efficiency with good accuracy and resolution. A good trade-off between focus performance and computational cost was found for the Fresnelet sparsity method. PMID- 27661595 TI - Femtosecond pulse generation with an a-cut Nd:CaYAlO4 disordered crystal. AB - We experimentally demonstrated a diode-pumped 587 fs ultrafast laser by using an a-cut Nd:CaYAlO4 crystal. Pumped by an 808 nm fiber-coupled laser diode, a stable continuous-wave mode-locked ultrafast laser was achieved with a semiconductor saturable absorber. The ultrafast pulses had a repetition rate of 75 MHz at the center wavelength of 1080.8 nm. A maximum average output power of the mode-locked laser reached 375 mW delivering a slope efficiency of 9%. PMID- 27661597 TI - Geometric analysis of influence of fringe directions on phase sensitivities in fringe projection profilometry. AB - In fringe projection profilometry, phase sensitivity is one of the important factors affecting measurement accuracy. A typical fringe projection system consists of one camera and one projector. To gain insight into its phase sensitivity, we perform in this paper a strict analysis in theory about the dependence of phase sensitivities on fringe directions. We use epipolar geometry as a tool to derive the relationship between fringe distortions and depth variations of the measured surface, and further formularize phase sensitivity as a function of the angle between fringe direction and the epipolar line. The results reveal that using the fringes perpendicular to the epipolar lines enables us to achieve the maximum phase sensitivities, whereas if the fringes have directions along the epipolar lines, the phase sensitivities decline to zero. Based on these results, we suggest the optimal fringes being circular-arc-shaped and centered at the epipole, which enables us to give the best phase sensitivities over the whole fringe pattern, and the quasi-optimal fringes, being straight and perpendicular to the connecting line between the fringe pattern center and the epipole, can achieve satisfyingly high phase sensitivities over whole fringe patterns in the situation that the epipole locates far away from the fringe pattern center. The experimental results demonstrate that our analyses are practical and correct, and that our optimized fringes are effective in improving the phase sensitivities and, further, the measurement accuracies. PMID- 27661598 TI - Ideal luminous efficacy and color spatial uniformity of package-free LED based on a packaging phosphor-coated geometry. AB - This paper presents the optical simulation of the luminous efficacy of radiation (LER) and color spatial uniformity (CSU) of a package-free white LED conducted to boost the LER and simultaneously improve the CSU. According to the simulation results, the main effect on the LER and CSU was the change in the geometrical ratio of phosphor coating. Regardless of the packaging size, when the ratio of the top coating to the sidewall coverage of the phosphor layer thickness was in the range from 0.9 to 1.1, the maximum LER and optimal CSU can be simultaneously obtained. Besides, effectively increasing the volume of the overall packaging dimension to be 30 times the size of the chip can enable a package-free LED to achieve 90% saturated maximum LER without affecting the CSU. PMID- 27661599 TI - Intensity-symmetric accelerating caustic beams. AB - We construct and generate symmetric accelerating caustic beams (ACBs) by using 3/2-order phase-only masks with elliptical contour based on optical caustics and diffraction theory. The symmetric ACBs are a type of bimodal accelerating caustic beam with two quasi-constant intensity peaks, very similar to the combination of two face-to-face Airy-like beams judging by appearance. Their fundamental optical morphology and force properties of particles in ACBs are subsequently provided. The unique optical properties of ACBs can be exploited for practical uses, such as accelerating electrons and clearing micrometer-sized particles as a laser micrometer-sized "water pump" instead of a laser micrometer-sized "snowblower" of accelerating Airy beams. PMID- 27661600 TI - Selective visual attention based clutter metric with human visual system adaptability. AB - Most existing clutter metrics are proposed based on fixed structural features and experienced weight measures. In this paper, we identify the clutter as selective visual attention effects and propose a type of clutter metric. First, adaptive structural features are extracted from the blocks with an edge-structure similarity to the target. Next, the confusing blocks are selected by the similarity threshold based on the attention guidance map. The clutter is estimated by quantifying the effects of confusing blocks on target acquisition performance. The comparative field experiments, with a Search_2 dataset, show that the proposed metric is consistent with the adaptability of the human visual system (HVS) and outperforms other metrics. PMID- 27661601 TI - Linear approximation of Rayleigh-Brillouin scattering spectra. AB - Rayleigh-Brillouin scattering is the basis of many remote sensing techniques, including high spectral resolution lidar measurements of aerosols and wind. Rayleigh-Brillouin spectra can be accurately estimated using physics-based models like the so-called Tenti's S6 and Pan's S7 models. Unfortunately, these are computationally expensive and can be the bottleneck for real-time lidar processing and iterative parameter estimation problems. This short article describes a very efficient linear approximation of the Rayleigh-Brillouin spectra based on Principal Component Analysis (PCA). Using PCA, the outputs of the above models can be approximated with very high accuracy using a single matrix multiplication. The described method can be applied to the output of any detailed scattering model, thus it can be used for a wide range of problems, e.g., for scattering from different gases (Air, N2, O2,...) and for different ranges of temperature and pressure. The precision of the approximation can be adapted to the requirements of the studied problem, and can easily exceed the actual accuracy of the reference models. PMID- 27661602 TI - 25 W/m2 collection efficiency solar-pumped Nd:YAG laser by a heliostat-parabolic mirror system. AB - A large aspheric fused silica lens was used to couple efficiently the concentrated solar radiation from the focal zone of a 1.5-m-diameter primary concentrator into a 4-mm-diameter, 35-mm-long Nd:YAG single-crystal rod within a conical pump cavity. Continuous-wave laser power of 29.3 W was measured, attaining 25.0 W/m2 solar laser collection efficiency, corresponding to a 19% increase over the previous record. Its laser beam figure of merit-the ratio between laser power and the product of Mx2, My2 beam quality factors-of 0.01 W is 1.6 times higher than that of a direct tracking solar laser with 30 W/m2 collection efficiency. A strong dependency of solar laser power on laser resonator cavity length was found. PMID- 27661603 TI - Nonsubsampled contourlet transform method for optical fringe pattern analysis in profilometry and interferometry. AB - A method based on a nonsubsampled contourlet transform, which is an overcomplete transform with multiresolution, directionality, and shift-invariance properties, is proposed to extract the fundamental frequency component of an optical fringe pattern in profilometry and interferometry. The nonsubsampled contourlet transform method overcomes the disadvantages of the original contourlet transform method, which lacks the shift-invariance property. Besides, it improves the frequency selectivity. A strategy is developed to automatically determine the optimal decomposition scale for removing the background intensity and suppressing the noise of the fringe pattern. The proposed method is precise, effective, and possesses a strong noise immune ability. Simulations and experiments verify the validity, and show the superiorities of the proposed method. PMID- 27661604 TI - Optical nonsubsampled contourlet transform. AB - The nonsubsampled contourlet transform (NSCT) is a fully shift-invariant, multiscale, and multidirectional expansion implemented in optics using the Fourier transform of its filters. In this paper, we propose a novel optical NSCT filter design method and the corresponding post-processing method to avoid the use of holographic techniques. The novel optical NSCT filter has real and non negative Fourier transforms. The input image is placed in the input plane of the VanderLugt 4f correlator, and these real and non-negative Fourier transform NSCT filters are placed in the frequency plane of the VanderLugt 4f correlator. Next, the NSCT result is captured by a CCD in the output plane of the VanderLugt 4f correlator, and its perfect reconstruction is theoretically possible, which is demonstrated by both simulation and optical experiment. PMID- 27661605 TI - Full-field 3D deformation measurement: comparison between speckle phase and displacement evaluation. AB - The objective of this paper is to describe a full-field deformation measurement method based on 3D speckle displacements. The deformation is evaluated from the slope of the speckle displacement function that connects the different reconstruction planes. For our experiment, a symmetrical arrangement with four illuminations parallel to the planes (x,z) and (y,z) was used. Four sets of speckle patterns were sequentially recorded by illuminating an object from the four directions, respectively. A single camera is used to record the holograms before and after deformations. Digital speckle photography is then used to calculate relative speckle displacements in each direction between two numerically propagated planes. The 3D speckle displacements vector is calculated as a combination of the speckle displacements from the holograms recorded in each illumination direction. Using the speckle displacements, problems associated with rigid body movements and phase wrapping are avoided. In our experiment, the procedure is shown to give the theoretical accuracy of 0.17 pixels yielding the accuracy of 2*10-3 in the measurement of deformation gradients. PMID- 27661606 TI - Highly sensitive Raman system for dissolved gas analysis in water. AB - The detection of dissolved gases in seawater plays an important role in ocean observation and exploration. As a potential technique for oceanic applications, Raman spectroscopy has already proved its advantages in the simultaneous detection of multiple species during previous deep-sea explorations. Due to the low sensitivity of conventional Raman measurements, there have been many reports of Raman applications on direct seawater detection in high-concentration areas, but few on undersea dissolved gas detection. In this work, we have presented a highly sensitive Raman spectroscopy (HSRS) system with a special designed gas chamber for small amounts of underwater gas extraction. Systematic experiments have been carried out for system evaluation, and the results have shown that the Raman signals obtained by the innovation of a near-concentric cavity was about 21 times stronger than those of conventional side-scattering Raman measurements. Based on this system, we have achieved a low limit of detection of 2.32 and 0.44 MUmol/L for CO2 and CH4, respectively, in the lab. A test out experiment has also been accomplished with a gas-liquid separator coupled to the Raman system, and signals of O2 and CO2 were detected after 1 h of degasification. This system may show potential for gas detection in water, and further work would be done for the improvement of in situ detection. PMID- 27661607 TI - Optimization of a dispersion-tuned wavelength-swept fiber laser for optical coherence tomography. AB - We optimized parameters of a dispersion-tuned wavelength-swept fiber laser by numerically analyzing dynamic characteristics. The optimized laser is experimentally demonstrated and applied to the swept-source optical coherence tomography (SS-OCT) system. The dispersion-tuned wavelength-swept laser (DT-WSL) is a unique tunable fiber laser, whose lasing wavelength can be tuned rapidly without any mechanical tunable filters. Although the wavelength of a DT-WSL can be swept rapidly and widely, the broadening of the instantaneous spectral width at a high sweep rate has been a critical drawback for SS-OCT applications. Numerical simulations have shown that higher modulation frequencies for active mode-locking lead to narrower instantaneous spectral widths. However, a lower modulation frequency is needed to achieve a wider wavelength tuning range. Pulse modulation is employed to solve the trade-off between instantaneous spectral width and wavelength tuning range. In this paper, the characteristics of a sinusoidally modulated and a pulse-modulated DT-WSL are compared numerically and experimentally. The numerical simulation results show that a pulse-modulated laser can achieve spectral widths as narrow as that of the sinusoidally modulated laser with >5 GHz modulation frequency, even when the pulse modulation frequency is as low as 500 MHz. We also study the difference in the laser characteristics with different sweep directions and discover that a positive wavelength sweep leads to a narrower instantaneous spectral width. We also experimentally confirmed that pulse modulation can indeed achieve a narrower spectral width, as expected from our numerical simulation results. The pulse-modulated DT-WSL is then used in an SS-OCT system and successfully achieves a coherence length of 1.3 mm, whereas that of a sinusoidally modulated DT-WSL is limited to only 0.7 mm. Furthermore, we experimentally compare the performance difference in OCT imaging with different wavelength sweep directions, and the results proved that it is advantageous to apply a positive wavelength sweep, as predicted by our numerical simulation. PMID- 27661608 TI - Temporal and frequency characteristics of a narrow light beam in sea water. AB - The structure of a light field in sea water excited by a unidirectional point sized pulsed source is studied by Monte Carlo technique. The pulse shape registered at the distances up to 120 m from the source on the beam axis and in its axial region is calculated with a time resolution of 1 ps. It is shown that with the increase of the distance from the source the pulse splits into two parts formed by components of various scattering orders. Frequency and phase responses of the beam are calculated by means of the fast Fourier transform. It is also shown that for higher frequencies, the attenuation of harmonic components of the field is larger. In the range of parameters corresponding to pulse splitting on the beam axis, the attenuation of harmonic components in particular spectral ranges exceeds the attenuation predicted by Bouguer law. In this case, the transverse distribution of the amplitudes of these harmonics is minimal on the beam axis. PMID- 27661610 TI - Genetic bases of dilated cardiomyopathy. AB - Cardiomyopathies represent a wide and heterogeneous group of diseases wherein a genetic cause has been consistently identified.Dilated cardiomyopathy (DCM) is characterized by ventricular dilation and progressive systolic dysfunction, and it is the most common form of cardiomyopathy.Causative genetic mutations have been identified in more than 40 genes encoding proteins belonging to different cellular structures and pathways.A great diversity of pathways has been implied in the pathogenesis of DCM, depending on the affected genes and on the dislodged intracellular structures or mechanisms.This review describes the major genes and focus on the pathophysiologic mechanisms of DCM, with a special consideration of the most recent discoveries in the field. PMID- 27661609 TI - Synthesis and Biological Activity of Highly Cationic Dendrimer Antibiotics. AB - The development of pathogenic bacteria resistant to current treatments is a major issue facing the world today. Here, the synthesis and biological activity of fourth generation poly(amidoamine) dendrimers decorated with 1-hexadecyl azoniabicylo[2.2.2]octane (C16-DABCO), a quaternary ammonium compound known to have antibacterial activity, are described. This highly cationic dendrimer antibiotic was tested against several Gram positive and Gram negative strains of pathogenic bacteria and exhibited activity against both. Higher activity toward the Gram positive strains that were tested was observed. After the antimicrobial activity was assessed, E. coli and B. cereus were subjected to a resistance selection study. This study demonstrated that a multivalent approach to antimicrobial design significantly reduces the likelihood of developing bacterial resistance. Highly cationic dendrimers were also used as pretreatment of a membrane to prevent biofilm formation. PMID- 27661611 TI - 'Precision and personalized medicine,' a dream that comes true? PMID- 27661613 TI - Fractionated Stereotactic Gamma Knife Radiosurgery for Large Brain Metastases: A Retrospective, Single Center Study. AB - PURPOSE: Stereotactic radiosurgery (SRS) is widely used for brain metastases but has been relatively contraindicated for large lesions (>3 cm). In the present study, we analyzed the efficacy and toxicity of hypofractionated Gamma Knife radiosurgery to treat metastatic brain tumors for which surgical resection were not considered as the primary treatment option. METHODS AND MATERIALS: Thirty-six patients, forty cases were treated with Gamma Knife-based fractionated SRS for three to four consecutive days with the same Leksell frame on their heads. The mean gross tumor volume was 18.3 cm3, and the median dose was 8 Gy at 50% isodose line with 3 fractions for three consecutive days (range, 5 to 11 Gy and 2 to 4 fractions for 2 to 4 consecutive days). Survival rates and prognostic factors were analyzed. RESULTS: The overall survival rate at one and two years was 66.7 and 33.1%, respectively. The median survival time was 16.2 months, and the local control rate was 90%. RTOG toxicity grade 1 was observed in 3 (8.3%) patients, grade 2 in 1 (2.7%) patient and grade 3 in 1 (2.7%) patient respectively. Radiation necrosis was developed in 1 (2.7%) patient. KPS scores and control of primary disease resulted in significant differences in survival. CONCLUSIONS: Our findings suggest that consecutive hypofractionated Gamma Knife SRS could be applied to large metastatic brain tumors with effective tumor control and low toxicity rates. PMID- 27661612 TI - Transcriptomic Study on Ovine Immune Responses to Fasciola hepatica Infection. AB - BACKGROUND: Fasciola hepatica is not only responsible for major economic losses in livestock farming, but is also a major food-borne zoonotic agent, with 180 million people being at risk of infection worldwide. This parasite is sophisticated in manipulating the hosts' immune system to benefit its own survival. A better understanding of the mechanisms underpinning this immunomodulation is crucial for the development of control strategies such as vaccines. METHODOLOGY/PRINCIPAL FINDINGS: This in vivo study investigated the global gene expression changes of ovine peripheral blood mononuclear cells (PBMC) response to both acute & chronic infection of F. hepatica, and revealed 6490 and 2364 differential expressed genes (DEGS), respectively. Several transcriptional regulators were predicted to be significantly inhibited (e.g. IL12 and IL18) or activated (e.g. miR155-5p) in PBMC during infection. Ingenuity Pathway Analysis highlighted a series of immune-associated pathways involved in the response to infection, including 'Transforming Growth Factor Beta (TGFbeta) signaling', 'Production of Nitric Oxide in Macrophages', 'Toll-like Receptor (TLRs) Signaling', 'Death Receptor Signaling' and 'IL17 Signaling'. We hypothesize that activation of pathways relevant to fibrosis in ovine chronic infection, may differ from those seen in cattle. Potential mechanisms behind immunomodulation in F. hepatica infection are a discussed. SIGNIFICANCE: In conclusion, the present study performed global transcriptomic analysis of ovine PBMC, the primary innate/adaptive immune cells, in response to infection with F. hepatica, using deep-sequencing (RNAseq). This dataset provides novel information pertinent to understanding of the pathological processes in fasciolosis, as well as a base from which to further refine development of vaccines. PMID- 27661615 TI - A Study of Tourism Dynamics in Three Italian Regions Using a Nonautonomous Integrable Lotka-Volterra Model. AB - This article is a first application of an integrable nonautonomous Lotka-Volterra (LV) model to the study of tourism dynamics. In particular, we analyze the interaction in terms of touristic flows among three Italian regions. Confirming an hypothesis advanced by recent theoretical works, we find that these regions not only compete against each other, but at times they also proceed in mutualism. Moreover, the kind and the intensity of the interaction changes over time, suggesting that dynamic models can play a vital role in the study of touristic flows. PMID- 27661616 TI - Procainamide Inhibits DNA Methylation and Alleviates Multiple Organ Dysfunction in Rats with Endotoxic Shock. AB - Excessive inflammatory and oxidative stress lead to circulatory failure, multiple organ dysfunction, and high mortality in patients with sepsis. Microbial infection-induced DNA hypermethylation is associated with the augmentation of inflammation and oxidative stress. In our previous study, the antiarrhythmic drug procainamide inhibits the expression of DNA methyltransferase 1 (DNMT1) and diminishes IL-6 levels in rats with rhabdomyolysis. Thus, we further evaluated the effects of procainamide on the development of circulatory failure and multiple organ dysfunction in rats with endotoxic shock. Male Wistar rats were intravenously infused with saline or lipopolysaccharide (LPS) followed by procainamide administration. The changes of hemodynamics, blood glucose, biochemical variables, and plasma nitric oxide (NO) levels were analyzed during the experimental period. At the end of experiments, animal organs were also obtained for examining superoxide production, neutrophil infiltration, and DNA methylation status. Our results showed that LPS induced circulatory failure, multiple organ dysfunction, and high mortality rate in endotoxemic rats. Overt neutrophil infiltration and superoxide production, accompanied by the elevations of DNMT1 and 5-methylcytosine levels in the lung of endotoxemic rats were also observed. Treatment of endotoxemic animals with procainamide not only inhibited the increased levels of DNMT1 and 5-methylcytosine but also ameliorated neutrophil infiltration and superoxide production in the lung. In addition, the anti-inflammatory gene, IL27RA, was down-regulated in the LPS group and up regulated in the LPS + Procainamide group. Procainamide also diminished IL27RA methylation in the lung of endotoxemic rat. Moreover, both DNMT inhibitors procainamide and hydralazine improved hypotension, hypoglycemia, and multiple organ dysfunction of LPS-treated rats. Thus, we suggest that the beneficial effects of procainamide could be attributed to the suppression of DNA methylation, neutrophil infiltration, superoxide production, and NO formation. It seems that this old drug may have new potential uses in infectious diseases, in particular, associated with endotoxemia. PMID- 27661614 TI - Development and Evaluation of Real Time RT-PCR Assays for Detection and Typing of Bluetongue Virus. AB - Bluetongue virus is the type species of the genus Orbivirus, family Reoviridae. Bluetongue viruses (BTV) are transmitted between their vertebrate hosts primarily by biting midges (Culicoides spp.) in which they also replicate. Consequently BTV distribution is dependent on the activity, geographic distribution, and seasonal abundance of Culicoides spp. The virus can also be transmitted vertically in vertebrate hosts, and some strains/serotypes can be transmitted horizontally in the absence of insect vectors. The BTV genome is composed of ten linear segments of double-stranded (ds) RNA, numbered in order of decreasing size (Seg-1 to Seg 10). Genome segment 2 (Seg-2) encodes outer-capsid protein VP2, the most variable BTV protein and the primary target for neutralising antibodies. Consequently VP2 (and Seg-2) determine the identity of the twenty seven serotypes and two additional putative BTV serotypes that have been recognised so far. Current BTV vaccines are serotype specific and typing of outbreak strains is required in order to deploy appropriate vaccines. We report development and evaluation of multiple 'TaqMan' fluorescence-probe based quantitative real-time type-specific RT-PCR assays targeting Seg-2 of the 27+1 BTV types. The assays were evaluated using orbivirus isolates from the 'Orbivirus Reference Collection' (ORC) held at The Pirbright Institute. The assays are BTV-type specific and can be used for rapid, sensitive and reliable detection / identification (typing) of BTV RNA from samples of infected blood, tissues, homogenised Culicoides, or tissue culture supernatants. None of the assays amplified cDNAs from closely related but heterologous orbiviruses, or from uninfected host animals or cell cultures. PMID- 27661618 TI - Community Pharmacists' Views and Practices Regarding Natural Health Products Sold in Community Pharmacies. AB - BACKGROUND: Reports of regulatory and evidentiary gaps have raised concerns about the marketing and use of natural health products (NHPs). The majority of NHPs offered for sale are purchased at a community pharmacy and pharmacists are "front line" health professionals involved in the marketing and provision of NHPs. To date, the involvement of pharmacists in pharmacy care involving NHPs and the degree to which concerns over the safety, efficacy, marketing and regulation of NHPs are addressed in pharmacy care in Canada have not been studied. METHODS: Using Qualtrics, a web-based data collection and analysis software, and a study instrument made up of fifteen (15) open-ended, closed and rating scale questions, we surveyed the attitudes and practices of 403 community pharmacists in the Canadian province of Alberta regarding NHPs offered for sale in community pharmacies. RESULTS: The majority of pharmacists surveyed (276; 68%) recommend NHPs to clients sometimes to very often. Vitamin D, calcium, multivitamins, prenatal vitamins, probiotics and fish oil and omega-3 fatty acids were the most frequently recommended NHPs. The most common indications for which NHPs are recommended include bone and musculoskeletal disorders, maintenance of general health, gastrointestinal disorders and pregnancy. Review articles published in the Pharmacist's Letter and Canadian Pharmacists Journal were the primary basis for recommending NHPs. The majority of pharmacists surveyed (339; 84%) recommend the use of NHPs concurrently with conventional drugs, while a significant number and proportion (125; 31%) recommend alternative use. Pharmacists in the study overwhelmingly reported providing counselling on NHPs to clients based on information obtained mainly from the Natural Medicines Comprehensive Database. CONCLUSIONS: The study findings indicate a high prevalence of pharmacy care relating to NHPs among study participants. Although pharmacists' practices around NHPs are consistent with the existing licensing framework, we found some involvement in problematic practices that necessitate further research and potential policy scrutiny. The study also uncovered patterns of recommendations, including sources relied on in recommending NHPs and in providing counselling to patients, that raise concerns about the quality and credibility of NHP-related care provided to pharmacy patrons. PMID- 27661617 TI - Social and Cultural Factors Affecting Maternal Health in Rural Gambia: An Exploratory Qualitative Study. AB - BACKGROUND: The high rate of maternal mortality reported in The Gambia is influenced by many factors, such as difficulties in accessing quality healthcare and facilities. In addition, socio-cultural practices in rural areas may limit the resources available to pregnant women, resulting in adverse health consequences. The aim of this study is to depict the gender dynamics in a rural Gambian context by exploring the social and cultural factors affecting maternal health. METHODS AND FINDINGS: Five focus group discussions that included 50 participants (aged 15-30 years, with at least one child) and six in-depth interviews with traditional birth attendants were conducted to explore perceptions of maternal health issues among rural women. The discussion was facilitated by guides focusing on issues such as how the women perceived their own physical health during pregnancy, difficulties in keeping themselves healthy, and health-related problems during pregnancy and delivery. The data resulting from the discussion was transcribed verbatim and investigated using a qualitative thematic analysis. In general, rural Gambian women did not enjoy privileges in their households when they were pregnant. The duties expected of them required pregnant women to endure heavy workloads, with limited opportunities for sick leave and almost nonexistent resources to access prenatal care. The division of labor between men and women in the household was such that women often engaged in non-remunerable field work with few economic resources, and their household duties during pregnancy were not alleviated by either their husbands or the other members of polygamous households. At the time of delivery, the decision to receive care by trained personnel was often beyond the women's control, resulting in birth-related complications. CONCLUSIONS: Our findings suggest that despite women's multiple roles in the household, their positions are quite unfavorable. The high maternal morbidity and mortality rate in The Gambia is related to practices associated with gender inequality. PMID- 27661619 TI - From Human Geography to Biological Invasions: The Black Rat Distribution in the Changing Southeastern of Senegal. AB - In the contemporary context of zoonosis emergence and spread, invasive species are a major issue since they represent potential pathogen hosts. Even though many progresses have been done to understand and predict spatial patterns of invasive species, the challenge to identify the underlying determinants of their distribution remains a central question in invasion biology. This is particularly exacerbated in the case of commensal species that strictly depend on humankind for dispersal and perennial establishment of new populations. The distribution of these species is predicted to be influenced by dispersal opportunities and conditions acting on establishment and proliferation, such as environmental characteristics, including spatio-temporal components of the human societies. We propose to contribute to the understanding of the recent spread of a major invasive rodent species, the black rat (Rattus rattus), in the changing southeastern of Senegal. We address the factors that promote the dispersal and distribution of this invasive rodent from the perspective of human geography. We first describe characteristics of human settlements in terms of social and spatial organization of human societies (i.e. economic activities, commercial and agricultural networks, roads connectivity). We then explore the relationship between these characteristics and the distribution of this invasive rodent. Finally we propose that historical and contemporary dynamics of human societies have contributed to the risk of invasion of the black rat. We argue that the diffusion processes of invasive species cannot be considered as a result of the spatial structure only (i.e. connectivity and distance), but as a part of the human territory that includes the social and spatial organization. Results suggest that the distribution of invasive rodents partly results from the contemporary and inherited human socio-spatial systems, beyond the existence of suitable ecological conditions that are classically investigated by biologists. PMID- 27661620 TI - Unusual Dynamics of Ligand Binding to the Heme Domain of the Bacterial CO Sens or Protein RcoM-2. AB - The aerobic Gram-negative bacterium Burkholderia xenovorans expresses two highly homologous carbon monoxide (CO)-responsive transcriptional regulators, RcoM-1 and RcoM-2, which display extraordinarily high CO affinities, even under oxygenic conditions. To gain insight into the origin and perspectives of this feature, we characterized the ligand-binding properties of the N-terminal, heme-binding Per/Arnt/Sim sensor domain of RcoM-2 by time-resolved spectroscopy. We show that upon photodissociation of the heme-ligand bond, CO geminately rebinds to the heme with picosecond time constants and more than 99% rebinding yield, an unprecedented property of native heme proteins. Remarkably, the rebinding kinetics speeds up when the protein motions are slowed by cooling or solvent viscosity. This indicates that the origin of the observed efficient rebinding is a protein-imposed CO configuration in the heme pocket that is highly favorable for binding, a feature strongly in contrast to that of hemoglobins. The binding of CO to the ferrous heme from the solvent requires dissociation of the methionine axial heme ligand. From the kinetics of ligand binding and the extreme stability of the CO complex, we deduce that the dissociation constant for CO is lower than 100 pM. Finally, we show that when the ferric complex is exposed to CO gas or a CO-releasing molecule under oxygenic conditions formation of the ferrous carbonyl complex can occur on a time scale of minutes in the presence of a redox mediator. These findings pave the way for possible applications of the RcoM-2 heme domain as a CO sensor and/or scavenger. PMID- 27661621 TI - Utilization of Routine Primary Care Services Among Dancers. AB - This study examines the current utilization of primary and preventive health care services among dancers in order to assess their self-reported primary care needs. Participants were 37 dancers from a variety of dance backgrounds who presented for a free dancer health screening in a large US metropolitan area (30 females, 7 males; mean age: 27.5 +/- 7.4 years; age range: 19 to 49 years; mean years of professional dancing: 6.4 +/- 5.4 years). Dancers were screened for use of primary care, mental health, and women's health resources using the Health Screen for Professional Dancers developed by the Task Force on Dancer Health. Most dancers had health insurance (62.2%), but within the last 2 years, only approximately half of them (54.1%) reported having a physical examination by a physician. Within the last year, 54.1% of dancers had had a dental check-up, and 56.7% of female dancers received gynecologic care. Thirty percent of female participants indicated irregular menstrual cycles, 16.7% had never been to a gynecologist, and 16.7% were taking birth control. Utilization of calcium and vitamin D supplementation was 27.0% and 29.7%, respectively, and 73.0% were interested in nutritional counseling. A high rate of psychological fatigue and sleep deprivation was found (35.1%), along with a concomitant high rate of self reported need for mental health counseling (29.7%). Cigarette and recreational drug use was low (5.4% and 5.4%); however, 32.4% engaged in binge drinking within the last year (based on the CDC definition). These findings indicate that dancers infrequently access primary care services, despite high self-reported need for nutritional, mental, and menstrual health counseling and treatment. More studies are warranted to understand dancers' primary health care seeking behavior. PMID- 27661622 TI - Surgical Treatment of the Accessory Navicular (Os Tibiale Externum) in Dancers: A Retrospective Case Series. AB - This study is to draw attention to a relatively common anatomical anomaly and its possible operative treatment in dancers. The accessory navicular, or os tibiale externum, is an accessory bone on the medial side of the navicular of the foot at the insertion of the posterior tibial tendon (PTT). It can cause obvious hyperpronation, medial foot pain, and a limited and painful releve in dancers. To the best of our knowledge, this is the first report on the operative treatment of the accessory navicular exclusively in dancers. Six dancers (10 feet) were treated in our clinic for a symptomatic accessory navicular Type II. Five of them (eight feet) underwent surgery, two unilaterally and three bilaterally (at the same time). All five had an excellent result at mean follow-up of 4.7 years, given that they fully resumed their professional dance activities without restriction, discomfort, or residual symptoms. One patient stopped dancing for unrelated reasons and became symptom free without further (surgical) treatment. Although no conclusions can be drawn from a retrospective case series and other treatment modalities were not considered, simple excision of a symptomatic accessory navicular Type II seems to be a good choice in dancers. PMID- 27661623 TI - Examining Standing Turnout with Two Measurement Methods During Dance Wellness Screening. AB - This study describes trends in mean standing functional turnout angles measured on a floor protractor (FP) and the Functional Footprint((r)) rotational instrument (RI) during routine clinical screens. Twenty-three professional ballet dancers, 26 collegiate modern students, and 46 ballet academy dancers participated in the study. All dancers demonstrated greater total turnout on the FP compared to the RI (p < 0.001), and the collegiate dancers had significantly smaller total turnout angles compared to both of the other groups (p < 0.001). A significant interaction between measurement method and training group (p = 0.047) on lower extremity asymmetry indicated that only in professionals left turnout angle was greater than right turnout angle on the RI (4.30 degrees +/- 6.64 degrees ) but not on the FP (0.17 degrees +/- 4.57 degrees ). It is concluded that turnout can be measured using either the FP or the RI measurement method, with recognition that FP measurements will be an average of 10 degrees greater than those on the RI. Lower extremity asymmetries in turnout angles may be better detected on the RI than the FP. PMID- 27661624 TI - A Survey of Injuries Affecting Pre-Professional Ballet Dancers. AB - A cross-sectional design was employed retrospectively to evaluate injuries self reported by 71 pre-professional ballet dancers over one season. Some of the descriptive findings of this survey were consistent with those of previous research and suggest particular demographic and injury trends in pre-professional ballet. These results include gender distribution, mean age and age range of participants, training hours, injury location, acute versus overuse injuries, as well as average number of physiotherapy treatments per dancer. Other results provide information that was heretofore unreported or inconsistent with previous investigations. These findings involved proportion of dancers injured, average number of injuries per dancer, overall injury incidence during an 8.5 month period, incidence rate by technique level, mean time loss per injury, proportion of recurrent injury, and activity practiced at time of injury. The results of univariate analyses revealed several significant findings, including a decrease in incidence rate of injury with increased months of experience in the pre professional program, dancers having lower injury risk in rehearsal and performance than in class, and a reduced risk of injury for dancers at certain technique levels. However, only this latter finding remained significant in multivariate analysis. The results of this study underscore the importance of determining injury rates by gender, technique level, and activity setting in addition to overall injury rates. They also point to the necessity of looking at both overall and individual dancer-based injury risks. PMID- 27661625 TI - An Exploration of the Perception of Dance and Its Relation to Biomechanical Motion: A Systematic Review and Narrative Synthesis. AB - In dance, the goals of actions are not always clearly defined. Investigations into the perceived quality of dance actions and their relation to biomechanical motion should give insight into the performance of dance actions and their goals. The purpose of this review was to explore and document current literature concerning dance perception and its relation to the biomechanics of motion. Seven studies were included in the review. The study results showed systematic differences between expert, non-expert, and novice dancers in biomechanical and perceptual measures, both of which also varied according to the actions expressed in dance. Biomechanical and perceptual variables were found to be correlated in all the studies in the review. Significant relations were observed between kinematic variables such as amplitude, speed, and variability of movement, and perceptual measures of beauty and performance quality. However, in general, there were no clear trends in these relations. Instead, the evidence suggests that perceptual ratings of dance may be specific to both the task (the skill of the particular action) and the context (the music and staging). The results also suggest that the human perceptual system is sensitive to skillful movements and neuromuscular coordination. Since the value perceived by audiences appears to be related to dance action goals and the coordination of dance elements, practitioners could place a priority on development and execution of those factors. PMID- 27661626 TI - Profound Hyperthermia After Postpartum Rectal Misoprostol Administration. PMID- 27661627 TI - In Reply. PMID- 27661628 TI - Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade. PMID- 27661629 TI - Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade. PMID- 27661630 TI - In Reply. PMID- 27661631 TI - Making Room at the Table for Obstetrics, Midwifery, and a Culture of Normalcy Within Maternity Care. PMID- 27661632 TI - In Reply. PMID- 27661633 TI - In Reply. PMID- 27661634 TI - Making Room at the Table for Obstetrics, Midwifery, and a Culture of Normalcy Within Maternity Care. PMID- 27661635 TI - In Reply. PMID- 27661636 TI - Ensuring Access to Safe, Legal Abortion in an Increasingly Complex Regulatory Environment. PMID- 27661637 TI - An Invitation to Join the Consortium on Thyroid and Pregnancy. PMID- 27661642 TI - Practice Bulletin No. 167 Summary: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus. AB - In the United States in 2013, there were an estimated 226,000 women and adolescents living with human immunodeficiency virus (HIV) infection (1). Women with HIV are living longer, healthier lives, so the need for routine and problem focused gynecologic care has increased. The purpose of this document is to educate clinicians about basic health screening and care, family planning, prepregnancy care, and managing common gynecologic problems for women and adolescents who are infected with HIV. For information on screening guidelines, refer to the American College of Obstetricians and Gynecologists' Committee Opinion No. 596, Routine Human Immunodeficiency Virus Screening (2). PMID- 27661643 TI - Practice Bulletin No. 168 Summary: Cervical Cancer Screening and Prevention. AB - The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID- 27661644 TI - Practice Bulletin No. 169 Summary: Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies. AB - The incidence of multifetal gestations in the United States has increased dramatically over the past several decades. The rate of twin births increased 76% between 1980 and 2009, from 18.9 to 33.3 per 1,000 births (1). The rate of triplet and higher-order multifetal gestations increased more than 400% during the 1980s and 1990s, peaking at 193.5 per 100,000 births in 1998, followed by a modest decrease to 153.4 per 100,000 births by 2009 (2). The increased incidence in multifetal gestations has been attributed to two main factors: 1) a shift toward an older maternal age at conception, when multifetal gestations are more likely to occur naturally, and 2) an increased use of assisted reproductive technology (ART), which is more likely to result in a multifetal gestation (3). PMID- 27661645 TI - Practice Bulletin No. 170 Summary: Critical Care in Pregnancy. AB - Critical care in pregnancy is a field that remains unevenly researched. Although there is a body of evidence to guide many recommendations in critical care, limited research specifically addresses obstetric critical care. The purpose of this document is to review the available evidence, propose strategies for care, and highlight the need for additional research. Much of the review will, of necessity, focus on general principles of critical care, extrapolating where possible to obstetric critical care. PMID- 27661647 TI - Practice Bulletin No. 172 Summary: Premature Rupture of Membranes. AB - Preterm delivery occurs in approximately 12% of all births in the United States and is a major factor that contributes to perinatal morbidity and mortality (1, 2). Preterm premature rupture of membranes (PROM) complicates approximately 3% of all pregnancies in the United States (3). The optimal approach to clinical assessment and treatment of women with term and preterm PROM remains controversial. Management hinges on knowledge of gestational age and evaluation of the relative risks of delivery versus the risks of expectant management (eg, infection, abruptio placentae, and umbilical cord accident). The purpose of this document is to review the current understanding of this condition and to provide management guidelines that have been validated by appropriately conducted outcome based research when available. Additional guidelines on the basis of consensus and expert opinion also are presented. PMID- 27661646 TI - Practice Bulletin No. 171 Summary: Management of Preterm Labor. AB - Preterm birth is the leading cause of neonatal mortality and the most common reason for antenatal hospitalization (1-4). In the United States, approximately 12% of all live births occur before term, and preterm labor preceded approximately 50% of these preterm births (5, 6). Although the causes of preterm labor are not well understood, the burden of preterm births is clear-preterm births account for approximately 70% of neonatal deaths and 36% of infant deaths as well as 25-50% of cases of long-term neurologic impairment in children (7-9). A 2006 report from the Institute of Medicine estimated the annual cost of preterm birth in the United States to be $26.2 billion or more than $51,000 per premature infant (10). However, identifying women who will give birth preterm is an inexact process. The purpose of this document is to present the various methods proposed to manage preterm labor and to review the evidence for the roles of these methods in clinical practice. Identification and management of risk factors for preterm labor are not addressed in this document. PMID- 27661648 TI - Committee Opinion No. 675 Summary: Management of Vulvar Intraepithelial Neoplasia. AB - Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. Although spontaneous regression has been reported, VIN should be considered a premalignant condition. Immunization with the quadrivalent or 9-valent human papillomavirus vaccine, which is effective against human papillomavirus genotypes 6, 11, 16, and 18, and 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively, has been shown to decrease the risk of vulvar high-grade squamous intraepithelial lesion (HSIL) (VIN usual type) and should be recommended for girls aged 11-12 years with catch-up through age 26 years if not vaccinated in the target age. There are no screening strategies for the prevention of vulvar cancer through early detection of vulvar HSIL (VIN usual type). Detection is limited to visual assessment with confirmation by histopathology when needed. Treatment is recommended for all women with vulvar HSIL (VIN usual type). Because of the potential for occult invasion, wide local excision should be performed if cancer is suspected, even if biopsies show vulvar HSIL. When occult invasion is not a concern, vulvar HSIL (VIN usual type) can be treated with excision, laser ablation, or topical imiquimod (off-label use). Given the relatively slow rate of progression, women with a complete response to therapy and no new lesions at follow-up visits scheduled 6 months and 12 months after initial treatment should be monitored by visual inspection of the vulva annually thereafter. PMID- 27661649 TI - Committee Opinion No. 676 Summary: Health Literacy to Promote Quality of Care. AB - Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand the basic health information and services they need to make appropriate health decisions. Multiple factors affect a patient's understanding of health information, including cultural factors, a physician's health know- ledge and communication skills, the demands of the situation, the environment in which the health information is being conveyed, and time constraints. The responsibility for recognizing and addressing the problem of limited health literacy lies with all entities in the health care system, from primary care physicians to community-based or public health organizations. Because of the potential effect of health literacy on patient outcomes, obstetrician-gynecologists should take the appropriate steps to ensure that they communicate in an understandable manner so patients can make informed decisions about their health care. PMID- 27661650 TI - Committee Opinion No. 677 Summary: Antenatal Corticosteroid Therapy for Fetal Maturation. AB - Corticosteroid administration before anticipated preterm birth is one of the most important antenatal therapies available to improve newborn outcomes. A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations. It also may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days, based on a family's decision regarding resuscitation, irrespective of membrane rupture status and regardless of fetal number. Administration of betamethasone may be considered in pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation at imminent risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids. A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days, and whose prior course of antenatal corticosteroids was administered more than 14 days previously. Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario. Continued surveillance of long-term outcomes after in utero corticosteroid exposure should be supported. Quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration are encouraged. PMID- 27661651 TI - Practice Bulletin No. 168: Cervical Cancer Screening and Prevention. AB - The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID- 27661652 TI - Practice Bulletin No. 169: Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies. AB - The incidence of multifetal gestations in the United States has increased dramatically over the past several decades. The rate of twin births increased 76% between 1980 and 2009, from 18.9 to 33.3 per 1,000 births (). The rate of triplet and higher-order multifetal gestations increased more than 400% during the 1980s and 1990s, peaking at 193.5 per 100,000 births in 1998, followed by a modest decrease to 153.4 per 100,000 births by 2009 (). The increased incidence in multifetal gestations has been attributed to two main factors: 1) a shift toward an older maternal age at conception, when multifetal gestations are more likely to occur naturally, and 2) an increased use of assisted reproductive technology (ART), which is more likely to result in a multifetal gestation (). PMID- 27661653 TI - Practice Bulletin No. 170: Critical Care in Pregnancy. AB - Critical care in pregnancy is a field that remains unevenly researched. Although there is a body of evidence to guide many recommendations in critical care, limited research specifically addresses obstetric critical care. The purpose of this document is to review the available evidence, propose strategies for care, and highlight the need for additional research. Much of the review will, of necessity, focus on general principles of critical care, extrapolating where possible to obstetric critical care. PMID- 27661654 TI - Practice Bulletin No. 171: Management of Preterm Labor. AB - Preterm birth is the leading cause of neonatal mortality and the most common reason for antenatal hospitalization . In the United States, approximately 12% of all live births occur before term, and preterm labor preceded approximately 50% of these preterm births . Although the causes of preterm labor are not well understood, the burden of preterm births is clear-preterm births account for approximately 70% of neonatal deaths and 36% of infant deaths as well as 25-50% of cases of long-term neurologic impairment in children . A 2006 report from the Institute of Medicine estimated the annual cost of preterm birth in the United States to be $26.2 billion or more than $51,000 per premature infant . However, identifying women who will give birth preterm is an inexact process. The purpose of this document is to present the various methods proposed to manage preterm labor and to review the evidence for the roles of these methods in clinical practice. Identification and management of risk factors for preterm labor are not addressed in this document. PMID- 27661655 TI - Practice Bulletin No. 172: Premature Rupture of Membranes. AB - Preterm delivery occurs in approximately 12% of all births in the United States and is a major factor that contributes to perinatal morbidity and mortality (1, 2). Preterm premature rupture of membranes (PROM) complicates approximately 3% of all pregnancies in the United States (3). The optimal approach to clinical assessment and treatment of women with term and preterm PROM remains controversial. Management hinges on knowledge of gestational age and evaluation of the relative risks of delivery versus the risks of expectant management (eg, infection, abruptio placentae, and umbilical cord accident). The purpose of this document is to review the current understanding of this condition and to provide management guidelines that have been validated by appropriately conducted outcome based research when available. Additional guidelines on the basis of consensus and expert opinion also are presented. PMID- 27661656 TI - Committee Opinion No.675: Management of Vulvar Intraepithelial Neoplasia. AB - Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. Although spontaneous regression has been reported, VIN should be considered a premalignant condition. Immunization with the quadrivalent or 9-valent human papillomavirus vaccine, which is effective against human papillomavirus genotypes 6, 11, 16, and 18, and 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively, has been shown to decrease the risk of vulvar high-grade squamous intraepithelial lesion (HSIL) (VIN usual type) and should be recommended for girls aged 11-12 years with catch-up through age 26 years if not vaccinated in the target age. There are no screening strategies for the prevention of vulvar cancer through early detection of vulvar HSIL (VIN usual type). Detection is limited to visual assessment with confirmation by histopathology when needed. Treatment is recommended for all women with vulvar HSIL (VIN usual type). Because of the potential for occult invasion, wide local excision should be performed if cancer is suspected, even if biopsies show vulvar HSIL. When occult invasion is not a concern, vulvar HSIL (VIN usual type) can be treated with excision, laser ablation, or topical imiquimod (off-label use). Given the relatively slow rate of progression, women with a complete response to therapy and no new lesions at follow-up visits scheduled 6 months and 12 months after initial treatment should be monitored by visual inspection of the vulva annually thereafter. PMID- 27661658 TI - Committee Opinion No.677: Antenatal Corticosteroid Therapy for Fetal Maturation. AB - Corticosteroid administration before anticipated preterm birth is one of the most important antenatal therapies available to improve newborn outcomes. A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations. It also may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days, based on a family's decision regarding resuscitation, irrespective of membrane rupture status and regardless of fetal number. Administration of betamethasone may be considered in pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation at imminent risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids. A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days, and whose prior course of antenatal corticosteroids was administered more than 14 days previously. Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario. Continued surveillance of long-term outcomes after in utero corticosteroid exposure should be supported. Quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration are encouraged. PMID- 27661657 TI - Committee Opinion No. 676: Health Literacy to Promote Quality of Care. AB - Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand the basic health information and services they need to make appropriate health decisions. Multiple factors affect a patient's understanding of health information, including cultural factors, a physician's health knowledge and communication skills, the demands of the situation, the environment in which the health information is being conveyed, and time constraints. The responsibility for recognizing and addressing the problem of limited health literacy lies with all entities in the health care system, from primary care physicians to community-based or public health organizations. Because of the potential effect of health literacy on patient outcomes, obstetrician-gynecologists should take the appropriate steps to ensure that they communicate in an understandable manner so patients can make informed decisions about their health care. PMID- 27661659 TI - Practice Bulletin No. 167: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus. AB - In the United States in 2013, there were an estimated 226,000 women and adolescents living with human immunodeficiency virus (HIV) infection (1). Women with HIV are living longer, healthier lives, so the need for routine and problem focused gynecologic care has increased. The purpose of this document is to educate clinicians about basic health screening and care, family planning, prepregnancy care, and managing common gynecologic problems for women and adolescents who are infected with HIV. For information on screening guidelines, refer to the American College of Obstetricians and Gynecologists' Committee Opinion No. 596, Routine Human Immunodeficiency Virus Screening (2). PMID- 27661660 TI - Adding Medicine During Machine Perfusion: A Breakthrough in Kidney Transplantation? PMID- 27661661 TI - Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial. AB - BACKGROUND: Degenerative disc disease often causes severe low-back pain, a public health problem with huge economic and life quality impact. Chronic cases often require surgery, which may lead to biomechanical problems and accelerated degeneration of the adjacent segments. Autologous mesenchymal stromal cells (MSC) treatments have shown feasibility, safety and strong indications of clinical efficacy. We present here a randomized, controlled trial using allogeneic MSC, which are logistically more convenient than autologous cells. METHODS: We randomized 24 patients with chronic back pain diagnosed with lumbar disk degeneration and unresponsive to conservative treatments into 2 groups. The test group received allogeneic bone marrow MSCs by intradiscal injection of 25 * 10 cells per segment under local anesthesia. The control group received a sham infiltration of paravertebral musculature with the anesthetic. Clinical outcomes were followed up for 1 year and included evaluation of pain, disability, and quality of life. Disc quality was followed up by magnetic resonance imaging. RESULTS: Feasibility and safety were confirmed and indications of clinical efficacy were identified. MSC-treated patients displayed a quick and significant improvement in algofunctional indices versus the controls. This improvement seemed restricted to a group of responders that included 40% of the cohort. Degeneration, quantified by Pfirrmann grading, improved in the MSC-treated patients and worsened in the controls. CONCLUSIONS: Allogeneic MSC therapy may be a valid alternative for the treatment of degenerative disc disease that is more logistically convenient than the autologous MSC treatment. The intervention is simple, does not require surgery, provides pain relief, and significantly improves disc quality. PMID- 27661663 TI - Management of macular oedema in diabetic patients undergoing cataract surgery. AB - PURPOSE OF REVIEW: The aim of this study was to describe all the treatment modalities used to prevent and manage macular oedema in diabetic patients undergoing cataract surgery. RECENT FINDINGS: Topical NSAIDs have been proposed to be an effective strategy to prevent postsurgical macular oedema (PME) in diabetic patients. The prophylactic use of intravitreal antivascular endothelial growth factors (anti-VEGF) drugs and steroids in these patients, even if effective, brings some concerns with regard to possible side effects. By contrast, in patients with a diagnosis of diabetic macular oedema (DME) at the time of cataract surgery, intravitreal therapy, both with anti-VEGF drugs and steroids, appears to be the best approach in order to control PME and achieve a good visual outcome. CONCLUSION: All diabetic patients undergoing cataract surgery should be treated with topical NSAIDs to prevent PME. Intravitreal anti VEGF drugs and steroids, combined with cataract surgery, should be reserved for patients with preexisting DME. PMID- 27661662 TI - Endophthalmitis after cataract surgery: epidemiology, risk factors, and evidence on protection. AB - PURPOSE OF REVIEW: After publication of the results of the European Society of Cataract and Refractive Surgery (ESCRS) study, there is a lot of enthusiasm for using intracameral antibiotics for the prevention of postcataract endophthalmitis. However, despite level 1 evidence, the practice has not been adopted universally. The aim of this review is to present a summary of the articles published in the last 18 months on this topic. RECENT FINDINGS: The published literature highlights that the incidence rate of endophthalmitis declined after 2007. Simultaneously, there is a rising trend for using intracameral injection of antibiotics at the conclusion of cataract surgery. Although various drugs have been used for this purpose, nearly all provide comparable protection. Industry has started manufacturing formulations for commercial availability of intracameral injection. Innovations are also ongoing to use intraocular lens for drug delivery and developing other intraocular drug delivery devices. SUMMARY: Endophthalmitis prevention is at an interesting crossroad. Although there is hesitation the intracameral injection of antibiotics is increasingly being adopted by physicians, which is likely to grow further with commercial availability of formulations. However, it will be important to be cautious and report all adverse reactions associated with this practice. PMID- 27661664 TI - Gastrointestinal mucormycosis after abdominal aortic aneurysm repair and prolonged hospitalization: A case report and review of the literature. AB - INTRODUCTION: Mucormycosis is a rare fungal infection typically affecting immunocompromised hosts. One form of the disease affects the gastrointestinal tract. PRESENTATION OF CASE: We present the case of a 70-year old patient with no recognized risk factors that developed gastrointestinal mucormycosis after urgent abdominal aortic aneurysm repair. DISCUSSION: There are several risk factors for this infection, such as hematological malignancies, solid organ or stem cell transplants and diabetes. The infectious agent causes thrombosis and necrosis of involved tissues and organs and carries a high mortality rate. CONCLUSION: Mucormycosis is an opportunistic infection which can sometimes affect the gastrointestinal tract. A high index of suspicion is necessary in order to make an early diagnosis and promptly start an appropriate treatment regimen. PMID- 27661665 TI - Pancreatic resection for renal cell carcinoma metastasis: An exceptionally rare coexistence. AB - INTRODUCTION: Pancreatic metastases are uncommon and only found in a minority of patients with widespread metastatic disease at autopsy. The most common primary cancer site resulting in pancreatic metastases is the kidney, followed by colorectal cancer, melanoma, breast cancer, lung carcinoma and sarcoma. PRESENTATION OF CASE: Herein, we report a 63-year-old male patient who presented 3.5 years after radical nephrectomy performed for renal cell carcinoma (RCC)-with a well-defined lobular, round mass at the body of the pancreas demonstrated by abdominal Magnetic Resonance Imaging (MRI). The patient underwent distal pancreatectomy combined with splenectomy and cholecystectomy. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for RCC marker, and negative for CD10 and CA19-9. A final diagnosis of clear RCC metastasizing to pancreas was obtained in view of the past history of RCC, microscopy and the immunoprofile. This was the second metachronous disease recurrence after a previous metastatic involvement of the liver, developed 19 months from the initial diagnosis. The patient has remained well at a 6 month follow up post-resection. DISCUSSION: Solitary pancreatic metastases may be misdiagnosed as primary pancreatic cancer. However, imaging including computed tomography (CT) and MRI, may discriminate between them. Surgical procedures could differentiate solitary metastasis from neuroendocrine neoplasms. The optimal resection strategy involves adequate resection margins and maximal tissue preservation of the pancreas. CONCLUSION: Recently, an increasing number of surgical resections have been performed in selected patients with limited metastatic disease to the pancreas. In addition, a rigid follow-up scheme, including endoscopic ultrasound (EUS) and CT is essential give patients a chance for a prolonged life. PMID- 27661666 TI - Pyridine-antipyrine appended indole derivative for selective recognition of Fe3+: Concentration dependent coloration. AB - Combination of pyridine, antipyrine and indole in a single molecule (L2) allows selective recognition of Fe3+ colorimetrically in CH3CN. The structure of L2 is confirmed from single crystal X-ray diffraction analysis. The probe displays two different visible bands at 541nm and 715nm in the presence of Fe3+, associated with two different colors, viz. green and pink-violet allowing determination of unknown Fe3+ concentration. Interestingly, removal of 2-picolyl group from indole N-center of L2 generates L3 that behaves similarly at low Fe3+ concentration (>0 to 1.1mM) but differently at higher Fe3+ concentration (>1.1mM), indicating involvement of pyridyl-N donor towards Fe3+, and hence different coordination environment around Fe3+ at higher concentration. PMID- 27661667 TI - Effect of Long Noncoding RNA H19 Overexpression on Intestinal Barrier Function and Its Potential Role in the Pathogenesis of Ulcerative Colitis. AB - BACKGROUND: Recently, long noncoding RNA (lncRNA) H19 has been reported to be related with VDR signaling and the development of inflammatory diseases including osteoarthritis. The aim of this study was to investigate the correlation between the expression level of H19 and VDR in ulcerative colitis (UC) tissues and to investigate the effect of H19 overexpression on intestinal epithelial barrier function. METHODS: The expression level of H19, miR-675-5p, and VDR in UC tissues and paired normal tissues collected from 12 patients with UC was investigated by quantitative real-time polymerase chain reaction. Caco-2 monolayers were used to test the effect of H19 and miR-675-5p overexpression on the intestinal epithelial barrier function and the status of tight junction proteins and VDR. Luciferase assay was used to validate the target site of miR-675-5p in the 3'UTR of VDR mRNA. RESULTS: The expression of H19 was found to be negatively correlated with the expression of VDR in UC tissues (r = 0.5369, P < 0.05). The expression of miR 675-5p was also found to be negatively correlated with the expression of VDR in UC tissues (r = 0.5233, P < 0.01). H19 overexpression increased Caco-2 monolayer permeability and decreased the expression of tight junction proteins and VDR, which was significantly attenuated by cotransfection with miR-675-5p inhibitors. The 3'UTR of VDR mRNA was validated to be one of the direct targets of miR-675 5p. CONCLUSIONS: This study reveals the destructive effect of H19 overexpression on intestinal epithelial barrier function and suggests a potential role of H19 in the development of UC. In addition, H19 overexpression may be one of the mechanisms underlying the decreased expression of VDR in UC tissues and the interaction between H19 and VDR signaling may provide potential therapeutic targets for UC. PMID- 27661668 TI - Colonic Lamina Propria Inflammatory Cells from Patients with IBD Induce the Nuclear Factor-E2 Related Factor-2 Thereby Leading to Greater Proteasome Activity and Apoptosis Protection in Human Colonocytes. AB - BACKGROUND: The antioxidant transcription factor Nrf2 confers broad cytoprotection and has a dual role in tumorigenesis. Enhancing proteasome activity is one mechanism by which Nrf2 can promote cancer development, e.g., colorectal cancer. This study investigated whether this potential oncogenic effect of Nrf2 emerges already from the epithelial adaptation to persistent oxidative stress during inflammatory bowel disease (IBD). METHODS: Reactive oxygen species (ROS)-producing inflammatory myeloid cells (IMCs) from colon tissue of patients with IBD were cocultured with human NCM460 colonocytes. ARE luciferase-, c-H2DCF-DA-assays, Western blotting, and quantitative polymerase chain reaction were performed for assessing Nrf2-activity, intracellular ROS level, and Nrf2-target gene expression. Proteasome activity was quantified by Suc LLVY-amido-4-methylcumarin-assay, and apoptosis by caspase-3/-7 assay and PARP1 Western blots. Nrf2, proteasome proteins, and IMCs were analyzed in IBD-tissues by immunohistochemistry. RESULTS: IMC-coculture caused a temporary increase of ROS in NCM460, followed by Nrf2 activation and elevated expression of ROS protecting enzymes (NQO1, GCLC). This was accompanied by Nrf2-dependent expression of proteasome proteins (PSMD4, PSMA5) and an enhanced proteasome activity in IMC-cocultured NCM460. Nrf2-siRNA or the ROS-scavenger Tiron blocked these alterations. Depending on Nrf2-induced proteasome activity, IMC-cocultured NCM460 or Colo320 cancer cells were less sensitive to apoptosis (TRAIL-/etoposide induced). Immunostaining of IBD-tissues confirmed Nrf2 activation in the colonic epithelium within inflamed areas, along with greater proteasome protein expression. CONCLUSIONS: IMC/NCM460-coculture experiments and immunohistochemistry of colonic tissues from patients with IBD reveal a Nrf2 dependent adaptation of colon epithelial cells to oxidative stress caused by inflammatory cells. This involves increased proteasome activity and apoptosis resistance that protect from tissue damage due to colitis on one hand, but on the other hand, may favor carcinogenesis. PMID- 27661669 TI - The Impact of Ostomy on Quality of Life and Functional Status of Crohn's Disease Patients. AB - BACKGROUND: The potential need for an ostomy is a main concern for patients with inflammatory bowel disease. We performed this study to evaluate the impact of a long-term ostomy (>=6 mo duration) on the functional status and specific patient reported outcomes in a population of patients with Crohn's disease (CD). METHODS: We performed a cross-sectional analysis within the Crohn's and Colitis Foundation of America Partners cohort. Bivariate analyses and logistic regression models were used to investigate associations between ostomy and various demographic, disease factors, and patient-reported outcomes for health-related quality of life. RESULTS: A total of 402 CD patients with ostomy for a minimum duration of 6 months were compared with 4331 CD patients with no ostomy. Patients with ostomy were more likely to be in clinical remission compared with those without ostomy, 48.5% versus 31.3%, respectively. Having an ostomy did not impact the overall health-related quality of life and was not associated with anxiety, depression, sleep disturbances, or reduced sexual interest and satisfaction. However, the presence of ostomy was associated with reduced social role satisfaction in both patients with controlled and active disease. Additionally, in the subset of patients who did not achieve clinical remission, those with ostomy experienced greater pain interference (odds ratio, 1.63; 95% confidence interval, 1.12-2.35) and fatigue (odds ratio, 1.66; 95% confidence interval, 1.15-2.39). CONCLUSIONS: Ostomy is well tolerated in CD patients, particularly when clinical remission is achieved. PMID- 27661671 TI - Emulating Anyonic Fractional Statistical Behavior in a Superconducting Quantum Circuit. AB - Anyons are exotic quasiparticles obeying fractional statistics, whose behavior can be emulated in artificially designed spin systems. Here we present an experimental emulation of creating anyonic excitations in a superconducting circuit that consists of four qubits, achieved by dynamically generating the ground and excited states of the toric code model, i.e., four-qubit Greenberger Horne-Zeilinger states. The anyonic braiding is implemented via single-qubit rotations: a phase shift of pi related to braiding, the hallmark of Abelian 1/2 anyons, has been observed through a Ramsey-type interference measurement. PMID- 27661672 TI - Multipartite Entanglement of a Two-Separable State. AB - We consider a six-partite, continuous-variable quantum state that we have effectively generated by the parametric down-conversion of a femtosecond frequency comb. We show that, though this state is two-separable, i.e., it does not exhibit "genuine entanglement," it is undoubtedly multipartite entangled. The consideration of not only the entanglement of individual mode decompositions, but also of combinations of those, solves the puzzle and exemplifies the importance of studying different categories of multipartite entanglement. PMID- 27661673 TI - Detection of 15 dB Squeezed States of Light and their Application for the Absolute Calibration of Photoelectric Quantum Efficiency. AB - Squeezed states of light belong to the most prominent nonclassical resources. They have compelling applications in metrology, which has been demonstrated by their routine exploitation for improving the sensitivity of a gravitational-wave detector since 2010. Here, we report on the direct measurement of 15 dB squeezed vacuum states of light and their application to calibrate the quantum efficiency of photoelectric detection. The object of calibration is a customized InGaAs positive intrinsic negative (p-i-n) photodiode optimized for high external quantum efficiency. The calibration yields a value of 99.5% with a 0.5% (k=2) uncertainty for a photon flux of the order 10^{17} s^{-1} at a wavelength of 1064 nm. The calibration neither requires any standard nor knowledge of the incident light power and thus represents a valuable application of squeezed states of light in quantum metrology. PMID- 27661674 TI - Metrology with PT-Symmetric Cavities: Enhanced Sensitivity near the PT-Phase Transition. AB - We propose and analyze a new approach based on parity-time (PT) symmetric microcavities with balanced gain and loss to enhance the performance of cavity assisted metrology. We identify the conditions under which PT-symmetric microcavities allow us to improve sensitivity beyond what is achievable in loss only systems. We discuss the application of PT-symmetric microcavities to the detection of mechanical motion, and show that the sensitivity is significantly enhanced near the transition point from unbroken- to broken-PT regimes. Our results open a new direction for PT-symmetric physical systems and it may find use in ultrahigh precision metrology and sensing. PMID- 27661675 TI - Cosmic-Ray Injection from Star-Forming Regions. AB - At present, all physical models of diffuse Galactic gamma-ray emission assume that the distribution of cosmic-ray sources traces the observed populations of either OB stars, pulsars, or supernova remnants. However, since H_{2}-rich regions host significant star formation and numerous supernova remnants, the morphology of observed H_{2} gas (as traced by CO line surveys) should also provide a physically motivated, high-resolution tracer for cosmic-ray injection. We assess the impact of utilizing H_{2} as a tracer for cosmic-ray injection on models of diffuse Galactic gamma-ray emission. We employ state-of-the-art 3D particle diffusion and gas density models, along with a physical model for the star-formation rate based on global Schmidt laws. Allowing a fraction, f_{H_{2}}, of cosmic-ray sources to trace the observed H_{2} density, we find that a theoretically well-motivated value f_{H_{2}}~0.20-0.25 (i) provides a significantly better global fit to the diffuse Galactic gamma-ray sky and (ii) highly suppresses the intensity of the residual gamma-ray emission from the Galactic center region. Specifically, in models utilizing our best global fit values of f_{H_{2}}~0.20-0.25, the spectrum of the galactic center gamma-ray excess is drastically affected, and the morphology of the excess becomes inconsistent with predictions for dark matter annihilation. PMID- 27661676 TI - First Measurements of High Frequency Cross-Spectra from a Pair of Large Michelson Interferometers. AB - Measurements are reported of the cross-correlation of spectra of differential position signals from the Fermilab Holometer, a pair of colocated 39 m long, high power Michelson interferometers with flat broadband frequency response in the MHz range. The instrument obtains sensitivity to high frequency correlated signals far exceeding any previous measurement in a broad frequency band extending beyond the 3.8 MHz inverse light-crossing time of the apparatus. The dominant but uncorrelated shot noise is averaged down over 2*10^{8} independent spectral measurements with 381 Hz frequency resolution to obtain 2.1*10^{-20}m/sqrt[Hz] sensitivity to stationary signals. For signal bandwidths Deltaf>11 kHz, the sensitivity to strain h or shear power spectral density of classical or exotic origin surpasses a milestone PSD_{deltah}=1 and r_{s}<=2. PMID- 27661700 TI - Anharmonic and Quantum Fluctuations in Molecular Crystals: A First-Principles Study of the Stability of Paracetamol. AB - Molecular crystals often exist in multiple competing polymorphs, showing significantly different physicochemical properties. Computational crystal structure prediction is key to interpret and guide the search for the most stable or useful form, a real challenge due to the combinatorial search space, and the complex interplay of subtle effects that work together to determine the relative stability of different structures. Here we take a comprehensive approach based on different flavors of thermodynamic integration in order to estimate all contributions to the free energies of these systems with density-functional theory, including the oft-neglected anharmonic contributions and nuclear quantum effects. We take the two main stable forms of paracetamol as a paradigmatic example. We find that anharmonic contributions, different descriptions of van der Waals interactions, and nuclear quantum effects all matter to quantitatively determine the stability of different phases. Our analysis highlights the many challenges inherent in the development of a quantitative and predictive framework to model molecular crystals. However, it also indicates which of the components of the free energy can benefit from a cancellation of errors that can redeem the predictive power of approximate models, and suggests simple steps that could be taken to improve the reliability of ab initio crystal structure prediction. PMID- 27661701 TI - Tunable Negative Thermal Expansion in Layered Perovskites from Quasi-Two Dimensional Vibrations. AB - We identify a quasi-two-dimensional (quasi-2D) phonon mode in the layered perovskite Ca_{3}Ti_{2}O_{7}, which exhibits an acoustic branch with quadratic dispersion. Using first-principles methods, we show this mode exhibits atomic displacements perpendicular to the layered [CaTiO_{3}]_{2} blocks comprising the structure and a negative Gruneisen parameter. Owing to these quasi-2D structural and dynamical features, we find that the mode can be utilized to realize unusual membrane effects, including a tunable negative thermal expansion (NTE) and a rare pressure-independent thermal softening of the bulk modulus. Detailed microscopic analysis shows that the NTE relies on strong intralayer Ti-O covalent bonding and weaker interlayer interactions, which is in contrast to conventional NTE mechanisms for perovskites, such as rigid-unit modes, structural transitions, and electronic or magnetic ordering. The general application of the quasi-2D lattice dynamics opens exciting avenues for the control of lattice dynamical and thermodynamic responses of other complex layered compounds through rational chemical substitution, as we show in A_{3}Zr_{2}O_{7} (A=Ca, Sr), and by heterostructuring. PMID- 27661702 TI - Quasi-One-Dimensional Metal-Insulator Transitions in Compound Semiconductor Surfaces. AB - Existing examples of Peierls-type 1D systems on surfaces involve depositing metallic overlayers on semiconducting substrates, in particular, at step edges. Here we propose a new class of Peierls system on the (101[over -]0) surface of metal-anion wurtzite semiconductors. When the anions are bonded to hydrogen or lithium atoms, we obtain rows of threefold coordinated metal atoms that act as one-atom-wide metallic structures. First-principles calculations show that the surface is metallic, and below a certain critical temperature the surface will condense to a semiconducting state. The idea of surface scaffolding is introduced in which the rows are constrained to move along simple up-down and/or sideways displacements, mirroring the paradigm envisioned in Peierls's description. We predict that this type of insulating state should be visible in the partially hydrogenated (101[over -]0) surface of many wurtzite compounds. PMID- 27661703 TI - Single-Layer Limit of Metallic Indium Overlayers on Si(111). AB - Density-functional calculations are used to identify one-atom-thick metallic In phases grown on the Si(111) surface, which have long been sought in quest of the ultimate two-dimensional (2D) limit of metallic properties. We predict two metastable single-layer In phases, one sqrt[7]*sqrt[3] phase with a coverage of 1.4 monolayer (ML; here 1 ML refers to one In atom per top Si atom) and the other sqrt[7]*sqrt[7] phase with 1.43 ML, which indeed agree with experimental evidences. Both phases reveal quasi-1D arrangements of protruded In atoms, leading to 2D-metallic but anisotropic band structures and Fermi surfaces. This directional feature contrasts with the free-electron-like In-overlayer properties that are known to persist up to the double-layer thickness, implying that the ultimate 2D limit of In overlayers may have been achieved in previous studies of double-layer In phases. PMID- 27661705 TI - Thermal Conductivity of the One-Dimensional Fermi-Hubbard Model. AB - We study the thermal conductivity of the one-dimensional Fermi-Hubbard model at a finite temperature using a density matrix renormalization group approach. The integrability of this model gives rise to ballistic thermal transport. We calculate the temperature dependence of the thermal Drude weight at half filling for various interaction strengths. The finite-frequency contributions originating from the fact that the energy current is not a conserved quantity are investigated as well. We report evidence that breaking the integrability through a nearest-neighbor interaction leads to vanishing Drude weights and diffusive energy transport. Moreover, we demonstrate that energy spreads ballistically in local quenches with initially inhomogeneous energy density profiles in the integrable case. We discuss the relevance of our results for thermalization in ultracold quantum-gas experiments and for transport measurements with quasi-one dimensional materials. PMID- 27661704 TI - Extreme Mechanics of Probing the Ultimate Strength of Nanotwinned Diamond. AB - Recently synthesized nanotwinned diamond (NTD) exhibits unprecedented Vickers hardness exceeding 200 GPa [Q. Huang et al., Nature (London) 510, 250 (2014)]. This extraordinary finding challenges the prevailing understanding of material deformation and stress response under extreme loading conditions. Here we unveil by first-principles calculations a novel indenter-deformation generated stress confinement mechanism that suppresses the graphitization or bond collapse failure modes commonly known in strong covalent solids, leading to greatly enhanced peak stress and strain range in the indented diamond lattice. Moreover, the twin boundaries in NTD promote a strong stress concentration that drives preferential bond realignments, producing a giant indentation strain stiffening. These results explain the exceptional indentation strength of NTD and offer insights into the extreme mechanics of the intricate interplay of the indenter and indented crystal in probing ultrahard materials. PMID- 27661706 TI - Engineering Polarons at a Metal Oxide Surface. AB - Polarons in metal oxides are important in processes such as catalysis, high temperature superconductivity, and dielectric breakdown in nanoscale electronics. Here, we study the behavior of electron small polarons associated with oxygen vacancies at rutile TiO_{2}(110), using a combination of low temperature scanning tunneling microscopy (STM), density functional theory, and classical molecular dynamics calculations. We find that the electrons are symmetrically distributed around isolated vacancies at 78 K, but as the temperature is reduced, their distributions become increasingly asymmetric, confirming their polaronic nature. By manipulating isolated vacancies with the STM tip, we show that particular configurations of polarons are preferred for given locations of the vacancies, which we ascribe to small residual electric fields in the surface. We also form a series of vacancy complexes and manipulate the Ti ions surrounding them, both of which change the associated electronic distributions. Thus, we demonstrate that the configurations of polarons can be engineered, paving the way for the construction of conductive pathways relevant to resistive switching devices. PMID- 27661707 TI - Glassy Dynamics in Disordered Electronic Systems Reveal Striking Thermal Memory Effects. AB - Memory is one of the unique qualities of a glassy system. The relaxation of a glass to equilibrium contains information on the sample's excitation history, an effect often refer to as "aging." We demonstrate that under the right conditions a glass can also possess a different type of memory. We study the conductance relaxation of electron glasses that are fabricated at low temperatures. Remarkably, the dynamics are found to depend not only on the ambient measurement temperature but also on the maximum temperature to which the system was exposed. Hence the system "remembers" its highest temperature. This effect may be qualitatively understood in terms of energy barriers and local minima in configuration space and therefore may be a general property of the glass state. PMID- 27661708 TI - Rashba-Edelstein Magnetoresistance in Metallic Heterostructures. AB - We report the observation of magnetoresistance originating from Rashba spin-orbit coupling (SOC) in a metallic heterostructure: the Rashba-Edelstein (RE) magnetoresistance. We show that the simultaneous action of the direct and inverse RE effects in a Bi/Ag/CoFeB trilayer couples current-induced spin accumulation to the electric resistance. The electric resistance changes with the magnetic-field angle, reminiscent of the spin Hall magnetoresistance, despite the fact that bulk SOC is not responsible for the magnetoresistance. We further found that, even when the magnetization is saturated, the resistance increases with increasing the magnetic-field strength, which is attributed to the Hanle magnetoresistance in this system. PMID- 27661709 TI - Plasmon Modes of Graphene Nanoribbons with Periodic Planar Arrangements. AB - Among their amazing properties, graphene and related low-dimensional materials show quantized charge-density fluctuations-known as plasmons-when exposed to photons or electrons of suitable energies. Graphene nanoribbons offer an enhanced tunability of these resonant modes, due to their geometrically controllable band gaps. The formidable effort made over recent years in developing graphene-based technologies is however weakened by a lack of predictive modeling approaches that draw upon available ab initio methods. An example of such a framework is presented here, focusing on narrow-width graphene nanoribbons, organized in periodic planar arrays. Time-dependent density-functional calculations reveal unprecedented plasmon modes of different nature at visible to infrared energies. Specifically, semimetallic (zigzag) nanoribbons display an intraband plasmon following the energy-momentum dispersion of a two-dimensional electron gas. Semiconducting (armchair) nanoribbons are instead characterized by two distinct intraband and interband plasmons, whose fascinating interplay is extremely responsive to either injection of charge carriers or increase in electronic temperature. These oscillations share some common trends with recent nanoinfrared imaging of confined edge and surface plasmon modes detected in graphene nanoribbons of 100-500 nm width. PMID- 27661710 TI - Electrical Conductivity through a Single Atomic Step Measured with the Proximity Induced Superconducting Pair Correlation. AB - Local disordered nanostructures in an atomically thick metallic layer on a semiconducting substrate play significant and decisive roles in transport properties of two-dimensional (2D) conductive systems. We measured the electrical conductivity through a step of monoatomic height in a truly microscopic manner by using as a signal the superconducting pair correlation induced by the proximity effect. The transport property across a step of a one-monolayer Pb surface metallic phase, formed on a Si(111) substrate, was evaluated by inducing the pair correlation around the local defect and measuring its response, i.e., the reduced density of states at the Fermi energy using scanning tunneling microscopy. We found that the step resistance has a significant contribution to the total resistance on a nominally flat surface. Our study also revealed that steps in the 2D metallic layer terminate the propagation of the pair correlation. Superconductivity is enhanced between the first surface step and the superconductor-normal-metal interface by reflectionless tunneling when the step is located within a coherence length. PMID- 27661711 TI - Landau-Level Mixing and Particle-Hole Symmetry Breaking for Spin Transitions in the Fractional Quantum Hall Effect. AB - The spin transitions in the fractional quantum Hall effect provide a direct measure of the tiny energy differences between differently spin-polarized states and thereby serve as an extremely sensitive test of the quantitative accuracy of the theory of the fractional quantum Hall effect, and, in particular, of the role of Landau-level mixing in lifting the particle-hole symmetry. We report on an accurate quantitative study of this physics, evaluating the effect of Landau level mixing in a nonperturbative manner using a fixed-phase diffusion Monte Carlo method. We find excellent agreement between our calculated critical Zeeman energies and the experimentally measured values. In particular, we find, as also do experiments, that the critical Zeeman energies for fractional quantum Hall states at filling factors nu=2-n/(2n+/-1) are significantly higher than those for nu=n/(2n+/-1), a quantitative signature of the lifting of particle-hole symmetry due to Landau-level mixing. PMID- 27661712 TI - Superlattice-Induced Insulating States and Valley-Protected Orbits in Twisted Bilayer Graphene. AB - Twisted bilayer graphene (TBLG) is one of the simplest van der Waals heterostructures, yet it yields a complex electronic system with intricate interplay between moire physics and interlayer hybridization effects. We report on electronic transport measurements of high mobility small angle TBLG devices showing clear evidence for insulating states at the superlattice band edges, with thermal activation gaps several times larger than theoretically predicted. Moreover, Shubnikov-de Haas oscillations and tight binding calculations reveal that the band structure consists of two intersecting Fermi contours whose crossing points are effectively unhybridized. We attribute this to exponentially suppressed interlayer hopping amplitudes for momentum transfers larger than the moire wave vector. PMID- 27661713 TI - Skyrmions and Hall Transport. AB - We derive a generalized set of Ward identities that captures the effects of topological charge on Hall transport. The Ward identities follow from the (2+1) dimensional momentum algebra, which includes a central extension proportional to the topological charge density. In the presence of topological objects like Skyrmions, we observe that the central term leads to a direct relation between the thermal Hall conductivity and the topological charge density. We extend this relation to incorporate the effects of a magnetic field and an electric current. The topological charge density produces a distinct signature in the electric Hall conductivity, which is identified in existing experimental data and yields further novel predictions. For insulating materials with translation invariance, the Hall viscosity can be directly determined from the Skyrmion density and the thermal Hall conductivity to be measured as a function of momentum. PMID- 27661714 TI - Vacancy-Induced Low-Energy States in Undoped Graphene. AB - We demonstrate that a nonzero concentration n_{v} of static, randomly placed vacancies in graphene leads to a density w of zero-energy quasiparticle states at the band center epsilon=0 within a tight-binding description with nearest neighbor hopping t on the honeycomb lattice. We show that w remains generically nonzero in the compensated case (exactly equal number of vacancies on the two sublattices) even in the presence of hopping disorder and depends sensitively on n_{v} and correlations between vacancy positions. For low, but not-too-low, |epsilon|/t in this compensated case, we show that the density of states rho(epsilon) exhibits a strong divergence of the form rho_{Dyson}(epsilon)~|epsilon|^{-1}/[log(t/|epsilon|)]^{(y+1)}, which crosses over to the universal low-energy asymptotic form (modified Gade-Wegner scaling) expected on symmetry grounds rho_{GW}(epsilon)~|epsilon|^{-1}e^{ b[log(t/|epsilon|)]^{2/3}} below a crossover scale epsilon_{c}?t. epsilon_{c} is found to decrease rapidly with decreasing n_{v}, while y decreases much more slowly. PMID- 27661715 TI - Superconducting Gap Anisotropy in Monolayer FeSe Thin Film. AB - Superconductivity originates from pairing of electrons near the Fermi energy. The Fermi surface topology and pairing symmetry are thus two pivotal characteristics of a superconductor. Superconductivity in one monolayer (1 ML) FeSe thin film has attracted great interest recently due to its intriguing interfacial properties and possibly high superconducting transition temperature over 65 K. Here, we report high-resolution measurements of the Fermi surface and superconducting gaps in 1 ML FeSe using angle-resolved photoemission spectroscopy. Two ellipselike electron pockets are clearly resolved overlapping with each other at the Brillouin zone corner. The superconducting gap is nodeless but moderately anisotropic, which puts strong constraint on determining the pairing symmetry. The gap maxima locate on the d_{xy} bands along the major axis of the ellipse and four gap minima are observed at the intersections of electron pockets. The gap maximum location combined with the Fermi surface geometry deviate from a single d wave, extended s-wave or s_{+/-} gap function, suggesting an important role of the multiorbital nature of Fermi surface and orbital-dependent pairing in 1 ML FeSe. The gap minima location may be explained by a sign change on the electron pockets, or a competition between intra- and interorbital pairing. PMID- 27661716 TI - Theoretical Model to Explain Excess of Quasiparticles in Superconductors. AB - Experimentally, the concentration of quasiparticles in gapped superconductors always largely exceeds the equilibrium one at low temperatures. Since these quasiparticles are detrimental for many applications, it is important to understand theoretically the origin of the excess. We demonstrate in detail that the dynamics of quasiparticles localized at spatial fluctuations of the gap edge becomes exponentially slow. This gives rise to the observed excess in the presence of a vanishingly weak nonequilibrium agent. PMID- 27661717 TI - Bicollinear Antiferromagnetic Order, Monoclinic Distortion, and Reversed Resistivity Anisotropy in FeTe as a Result of Spin-Lattice Coupling. AB - The bicollinear antiferromagnetic order experimentally observed in FeTe is shown to be stabilized by the coupling g[over ~]_{12} between monoclinic lattice distortions and the spin-nematic order parameter with B_{2g} symmetry, within a three-orbital spin-fermion model studied with Monte Carlo techniques. A finite but small value of g[over ~]_{12} is required, with a concomitant lattice distortion compatible with experiments, and a tetragonal-monoclinic transition strongly first order. Remarkably, the bicollinear state found here displays a planar resistivity with the "reversed" puzzling anisotropy discovered in transport experiments. Orthorhombic distortions are also incorporated, and phase diagrams interpolating between pnictides and chalcogenides are presented. We conclude that the spin-lattice coupling we introduce is sufficient to explain the challenging properties of FeTe. PMID- 27661718 TI - Universal Faraday Rotation in HgTe Wells with Critical Thickness. AB - The universal value of the Faraday rotation angle close to the fine structure constant (alpha~1/137) is experimentally observed in thin HgTe quantum wells with a thickness on the border between trivial insulating and the topologically nontrivial Dirac phases. The quantized value of the Faraday angle remains robust in the broad range of magnetic fields and gate voltages. Dynamic Hall conductivity of the holelike carriers extracted from the analysis of the transmission data shows a theoretically predicted universal value of sigma_{xy}=e^{2}/h, which is consistent with the doubly degenerate Dirac state. On shifting the Fermi level by the gate voltage, the effective sign of the charge carriers changes from positive (holes) to negative (electrons). The electronlike part of the dynamic response does not show quantum plateaus and is well described within the classical Drude model. PMID- 27661719 TI - Collective Motion of Microorganisms in a Viscoelastic Fluid. AB - We study the collective motion of a suspension of rodlike microswimmers in a two dimensional film of viscoelastic fluids. We find that the fluid elasticity has a small effect on a suspension of pullers, while it significantly affects the pushers. The attraction and orientational ordering of the pushers are enhanced in viscoelastic fluids. The induced polymer stresses break down the large-scale flow structures and suppress velocity fluctuations. In addition, the energy spectra and induced mixing in the suspension of pushers are greatly modified by fluid elasticity. PMID- 27661720 TI - Rich Polymorphic Behavior of Wigner Bilayers. AB - Self-assembly into target structures is an efficient material design strategy. Combining analytical calculations and computational techniques of evolutionary and Monte Carlo types, we report about a remarkable structural variability of Wigner bilayer ground states, when charges are confined between parallel charged plates. Changing the interlayer separation, or the plate charge asymmetry, a cascade of ordered patterns emerges. At variance with the symmetric case phenomenology, the competition between commensurability features and charge neutralization leads to long range attraction, appearance of macroscopic charges, exotic phases, and nonconventional phase transitions with distinct critical indices, offering the possibility of a subtle, but precise and convenient control over patterns. PMID- 27661721 TI - Infrared Action Spectroscopy of Low-Temperature Neutral Gas-Phase Molecules of Arbitrary Structure. AB - We demonstrate a technique for IR action spectroscopy that enables measuring IR spectra in a background-free fashion for low-temperature neutral gas-phase molecules of arbitrary structure. The method is exemplified experimentally for N methylacetamide molecules in the mid-IR spectral range of 1000-1800 cm^{-1}, utilizing the free electron laser FELIX. The technique involves the resonant absorption of multiple mid-IR photons, which induces molecular dissociation. The dissociation products are probed with 10.49 eV vacuum ultraviolet photons and analyzed with a mass spectrometer. We also demonstrate the capability of this method to record, with unprecedented ease, mid-IR spectra for the molecular associates, such as clusters and oligomers, present in a molecular beam. In this way the mass-selected spectra of low-temperature gas-phase dimers and trimers of N-methylacetamide are measured in the full amide I-III range. PMID- 27661722 TI - Role of bovine serum albumin and humic acid in the interaction between SiO2 nanoparticles and model cell membranes. AB - Silica nanoparticles (SiO2 NPs) can cause health hazard after their release into the environment. Adsorption of natural organic matter and biomolecules on SiO2 NPs alters their surface properties and cytotoxicity. In this study, SiO2 NPs were treated by bovine serum albumin (BSA) and humic acid (HA) to study their effects on the integrity and fluidity of model cell membranes. Giant and small unilamellar vesicles (GUVs and SUVs) were prepared as model cell membranes in order to avoid the interference of cellular activities. The microscopic observation revealed that the BSA/HA treated (BSA-/HA-) SiO2 NPs took more time to disrupt membrane than untreated-SiO2 NPs, because BSA/HA adsorption covered the surface SiOH/SiO- groups and weakened the interaction between NPs and phospholipids. The deposition of SiO2 NPs on membrane was monitored by a quartz crystal microbalance with dissipation (QCM-D). Untreated- and HA-SiO2 NPs quickly disrupted the SUV layer on QCM-D sensor; BSA-SiO2 NPs attached on the membranes but only caused slow vesicle disruption. Untreated-, BSA- and HA-SiO2 NPs all caused the gelation of the positively-charged membrane, which was evaluated by the generalized polarity values. HA-SiO2 NPs caused most serious gelation, and BSA-SiO2 NPs caused the least. Our results demonstrate that the protein adsorption on SiO2 NPs decreases the NP-induced membrane damage. PMID- 27661723 TI - Removal of phyto-accessible copper from contaminated soils using zero valent iron amendment and magnetic separation methods: Assessment of residual toxicity using plant and MetPLATETM studies. AB - Zero valent iron (ZVI) has been widely tested and used in remediation of both contaminated soils and groundwater, and in general, the in situ amendment of the contaminated media is used as remediation approach. However, concerns remain as to the potential detrimental effects of both the immobilized ZVI and the adsorbed pollutants as the treated system could undergo transformations over time. Accordingly, plans for soil remediation by in situ immobilization of sorbents should include a long-term monitoring of the treated systems. Here, we report on a comparative study in which artificially Cu-contaminated sandy and organic soils characterized by different metal binding capacities were treated by either (i) in situ immobilization of ZVI in the soils, or (ii) by a ZVI amendment followed by magnetic retrieval of formed ZVI-Cu complexes prior to plant growth studies. The latter relies on the combination of the high metal adsorption capacity and magnetism of ZVI. Two plant species, Lactuca sativa (lettuce) and Brassica juncea (Indian mustard) were used to assess the efficiency of the two treatment methods in eliminating the bioavailable fraction of Cu. Overall, the results showed that, if soil remediation by in situ immobilization reduces the bio-accessible fraction of Cu, treatment using ZVI amendment followed by magnetic separation performs better. The latter resulted in less Cu accumulated in the shoots and roots of plants. In parallel to the plant growth study, we used MetPLATETM, a short-term bioassay based on the inhibition of the beta-galactosidase enzyme by the bioavailable fraction of heavy metal cations, to predict the efficiency of the two treatment methods with regard to the elimination of Cu phyto-toxicity. The results of the bioassay confirmed the trends of phyto-toxicity results, suggesting that MetPLATETM could be an adequate alternative to the more expensive, labor intensive, and time consuming plant growth studies. PMID- 27661724 TI - Multiscale correlations of iron phases and heavy metals in technogenic magnetic particles from contaminated soils. AB - Technogenic magnetic particles (TMPs) are carriers of heavy metals and organic contaminants, which derived from anthropogenic activities. However, little information on the relationship between heavy metals and TMP carrier phases at the micrometer scale is available. This study determined the distribution and association of heavy metals and magnetic phases in TMPs in three contaminated soils at the micrometer scale using micro-X-ray fluorescence (MU-XRF) and micro-X ray absorption near-edge structure (MU-XANES) spectroscopy. Multiscale correlations of heavy metals in TMPs were elucidated using wavelet transform analysis. MU-XRF mapping showed that Fe was enriched and closely correlated with Co, Cr, and Pb in TMPs from steel industrial areas. Fluorescence mapping and wavelet analysis showed that ferroalloy was a major magnetic signature and heavy metal carrier in TMPs, because most heavy metals were highly associated with ferroalloy at all size scales. Multiscale analysis revealed that heavy metals in the TMPs were from multiple sources. Iron K-edge MU-XANES spectra revealed that metallic iron, ferroalloy, and magnetite were the main iron magnetic phases in the TMPs. The relative percentage of these magnetic phases depended on their emission sources. Heatmap analysis revealed that Co, Pb, Cu, Cr, and Ni were mainly derived from ferroalloy particles, while As was derived from both ferroalloy and metallic iron phases. Our results indicated the scale-dependent correlations of magnetic phases and heavy metals in TMPs. The combination of synchrotron based X-ray microprobe techniques and multiscale analysis provides a powerful tool for identifying the magnetic phases from different sources and quantifying the association of iron phases and heavy metals at micrometer scale. PMID- 27661725 TI - The impact of cerium oxide nanoparticles on the salt stress responses of Brassica napus L. AB - Dwindling high quality water resources and growing population are forcing growers to irrigate crops with water of high salinity. It is well recognized that salinity negatively affects plant physiology and biochemistry, and represents one of the most serious threats to crop production and food security. Meanwhile, engineered nanoparticles (ENPs) are increasingly detected in irrigation water and agricultural soils due to the rapid advancement of nanotechnology. Previous research has demonstrated that ENPs such as cerium oxide nanoparticles (CeO2-NPs) exert significant impact on plant growth and production. However, almost all previous studies were conducted in well controlled environment. Knowledge on how ENPs affect plant development in a stressed condition is almost empty. The goal of the present study was to understand the physiological and biochemical changes in Brassica napus L. (canola) cv. 'Dwarf Essex' under synergistic salt stress and CeO2-NPs effects. Two salinity levels: 0 (control) and 100 mM NaCl, and three CeO2-NPs concentrations: 0 (control), 200 and 1000 mg kg-1 dry sand and clay mixture, were employed. As expected, 100 mM of NaCl significantly hindered plant growth and negatively affected the physiological processes of canola. Plants treated with CeO2-NPs had higher plant biomass, exhibited higher efficiency of the photosynthetic apparatus and less stress in both fresh water and saline water irrigation conditions Overall, our results demonstrated that CeO2-NPs led to changes in canola growth and physiology which improved the plant salt stress response but did not completely alleviate the salt stress of canola. PMID- 27661726 TI - Ecotoxicity of cadmium in a soil collembolan-predatory mite food chain: Can we use the 15N labeled litter addition method to assess soil functional change? AB - Effects of cadmium (Cd) on predator-prey relationships and soil ecological function are poorly understood and there are few methods available to measure soil functional change. Thus, we structured a soil-dwelling food chain containing the predatory mite Hypoaspis aculeifer and its collembolan prey Folsomia candida to study the effects of Cd exposure for eight weeks in a spiked soil aged for five years. The 15N labeled litter was added as food to analyze the change in nitrogen (N) transfer content. H. aculeifer reproduction and growth and the survival and reproduction of F. candida were all negatively affected by Cd exposure, and H. aculeifer reproduction was the most sensitive parameter. The sensitivity responses of F. candida and H. aculeifer were different from those using the previous single species test. The results suggest that predator-prey interactions might influence the toxicity of Cd by predation and food restriction. Cadmium lethal body concentrations of adults and juveniles of F. candida and H. aculeifer juveniles were 500-600, 180-270 and 8-10 MUg g-1, respectively. The content of N transfer from litter to animals in the food chain decreased significantly with increasing soil Cd concentration between 100 and 400 mg kg-1. The results suggest that the 15N labeled litter addition method is potentially useful for quantitative assessment of soil functional change for further risk assessment purposes. PMID- 27661727 TI - Analysis of fullerenes in soils samples collected in The Netherlands. AB - Fullerenes are carbon based nanoparticles that may enter the environment as a consequence of both natural processes and human activities. Although little is known about the presence of these chemicals in the environment, recent studies suggested that soil may act as a sink. The aim of the present work was to investigate the presence of fullerenes in soils collected in The Netherlands. Samples (n = 91) were taken from 6 locations and analyzed using a new developed LC-QTOF-MS method. The locations included highly trafficked and industrialized as well as urban and natural areas. In general, C60 was the most abundant fullerene found in the environment, detected in almost a half of the samples and at concentrations in the range of ng/kg. Other fullerenes such as C70 and an unknown structure containing a C60 cage were detected to a lower extent. The highest concentrations were found in the proximity of combustion sites such as a coal power plant and an incinerator, suggesting that the nanoparticles were unintentionally produced during combustions processes and reached the soil through atmospheric deposition. Consistent with other recent studies, these results show that fullerenes are widely present in the environment and that the main route for their entrance may be due to human activities. These data will be helpful in the understanding of the distribution of fullerenes in the environment and for the study of their behavior and fate in soil. PMID- 27661728 TI - Relative importance of microplastics as a pathway for the transfer of hydrophobic organic chemicals to marine life. AB - It has been hypothesised that, if ingested, plastic debris could act as vector for the transfer of chemical contaminants from seawater to organisms, yet modelling suggest that, in the natural environment, chemical transfer would be negligible compared to other routes of uptake. However, to date, the models have not incorporated consideration of the role of gut surfactants, or the influence of pH or temperature on desorption, whilst experimental work has shown that these factors can enhance desorption of sorbed contaminants several fold. Here, we modelled the transfer of sorbed organic contaminants dichlorodiphenyltrichloroethane (DDT), phenanthrene (Phe) and bis-2-ethylhexyl phthalate (DEHP) from microscopic particles of polyvinylchloride (PVC) and polyethylene (PE) to a benthic invertebrate, a fish and a seabird using a one compartment model OMEGA (Optimal Modelling for EcotoxicoloGical Applications) with different conditions of pH, temperature and gut surfactants. Environmental concentrations of contaminants at the bottom and the top of published ranges were considered, in combination with ingestion of either 1 or 5% by weight of plastic. For all organisms, the combined intake from food and water was the main route of exposure for Phe, DEHP and DDT with a negligible input from plastic. For the benthic invertebrate, predictions including the presence of contaminated plastic resulted in very small increases in the internal concentrations of DDT and DEHP, while the net change in the transfer of Phe was negligible. While there may be scenarios in which the presence of plastic makes a more important contribution, our modelling study suggests that ingestion of microplastic does not provide a quantitatively important additional pathway for the transfer of adsorbed chemicals from seawater to biota via the gut. PMID- 27661729 TI - A simultaneous analysis method of polycyclic aromatic hydrocarbons, nicotine, cotinine and metals in human hair. AB - Polycyclic aromatic hydrocarbons (PAHs), nicotine, cotinine, and metals in human hair have been used as important environmental exposure markers. We aimed to develop a simple method to simultaneously analyze these pollutants using a small quantity of hair. The digestion performances of tetramethylammonium hydroxide (TMAH) and sodium hydroxide (NaOH) for human hair were compared. Various solvents or their mixtures including n-hexane (HEX), dichloromethane (DCM) and trichloromethane (TCM), HEX:DCM32 (3/2) and HEX:TCM73 (7/3) were adopted to extract organics. The recoveries of metals were determined under an optimal operation of digestion and extraction. Our results showed that TMAH performed well in dissolving human hair and even better than NaOH. Overall, the recoveries for five solutions were acceptable for PAHs, nicotine in the range of 80%-110%. Except for HEX, other four extraction solutions had acceptable extraction efficiency for cotinine from HEX:TCM73 (88 +/- 4.1%) to HEX:DCM32 (100 +/- 2.8%). HEX:DCM32 was chosen as the optimal solvent in consideration of its extraction efficiency and lower density than water. The recoveries of 12 typical major or trace metals were mainly in the range of 90%-110% and some of them were close to 100%. In conclusion, the simultaneous analysis of PAHs, nicotine, cotinine, and metals was feasible. Our study provided a simple and low-cost technique for environmental epidemiological studies. PMID- 27661730 TI - Urban PM2.5 oxidative potential: Importance of chemical species and comparison of two spectrophotometric cell-free assays. AB - Oxidative potential (OP) of particulate matter (PM) - defined as the capacity of PM to oxidize target molecules generating reactive oxygen species (ROS) - has been proposed as a more health relevant metric than PM mass. In this study two cell-free methods were used to assess the OP of PM filters collected at an urban site and to evaluate correlation with PM mass and PM composition. Among the different assays existing, two inexpensive and user-friendly methods were used both based on spectrophotometric measurements of depletion rate of target reagents oxidized by redox-active species present in PM. One assay measures the consumption of dithiothreitol (OPDTT) and the other the ascorbate (OPAA). Although both assays respond to the same redox-active species, i.e., quinones and transition metals, no correlations were found between OPDTT and OPAA responses to compounds standard solutions as well as to ambient samples. When expressed in relation to air volume, OPDTT m-3 strongly correlates with PM2.5 mass whereas no correlation was found for OPAA m-3 with PM2.5. When expressed on mass basis, both OPDTT MUg-1 and OPAA MUg-1 show a strong dependence on the sample composition, with higher OP for summer samples. OPDTT m-3 were highly correlated with the determined metals (Cu, Zn, Cr, Fe, Ni, Mn) whereas OPAA m-3 showed only moderate correlation with Cu and Mn. Thus, the two assays could potentially provide complementary information on oxidative potential characteristic of PM. Consequently, the combination of the two approaches can strengthen each other in giving insight into the contribution of chemical composition to oxidative properties of PM, which can subsequently be used to study health effects. PMID- 27661731 TI - Broadening Our Understanding of Caregiver Outcomes Across Cultures: What Does "Caregiver Relationship" Actually Capture? PMID- 27661732 TI - Biomechanical Comparison of Superior Versus Anterior Plate Position for Fixation of Distal Clavicular Fractures: A New Model. AB - OBJECTIVES: Although most clavicular fractures are amenable to nonoperative management, metadiaphyseal fractures are considerably more complex, with rates of suboptimal healing as high as 75% when treated nonoperatively. The poor results are ascribed to the deforming forces on the distal clavicle from the surrounding muscles and the weight of the arm. It recently has been noted that some operative fixations of these fractures are also failing when a standard superiorly placed plate is used. We hypothesized that anterior plating, when compared with superior plating, improves the strength and durability of the construct by redirecting the axis of the major deforming force across rather than in line with the screws of the construct. METHODS: Six pairs of fresh-frozen human cadaveric clavicles with the scapula attached by the coracoclavicular ligaments were osteotomized just medial to the ligaments and plated with a standard 3.5-mm limited-contact dynamic compression plate. Specimens were potted and mounted on a materials testing system machine, preserving the anatomic relationship of the clavicle and scapula. They were then loaded through the coracoclavicular ligaments to mimic the weight of the arm pulling inferiorly. Each specimen was loaded with 375 N at 1 Hz for 2000 cycles. Sequential loading was then applied at 25-N intervals until failure. Statistical analysis was performed using a Wilcoxon signed-rank test. RESULTS: The superiorly plated specimens failed after fewer cycles and with lower force than the anteriorly plated specimens. The median number of cycles to failure was 2082 for anterior plated specimens and 50 for superiorly plated (P = 0.028). The median load to failure was 587.5 N in the anterior group and 375 N in the superior group (P = 0.035). The median stiffness was 46.13 N/mm for anterior and 40.45 N/mm for superior (P = 0.375) plates. CONCLUSIONS: Anteriorly plated distal third clavicular fractures have superior strength and durability compared with fractures plated superiorly when using a physician-contoured, 3.5-mm, limited contact, dynamic compression plate in this cadaver model. PMID- 27661733 TI - A Useful Preoperative Planning Technique for Transiliac-Transsacral Screws. AB - Stabilization of posterior pelvic ring injuries is increasingly performed using percutaneously placed iliosacral and transiliac-transsacral screws. Understanding the unique and specific anatomical variations present in each patient is paramount. Multiple methods of evaluating potential osseous fixation pathways for screw placement exist, but many require specific imaging protocols, specialized software, or modification of data. Not all surgeons and institutions have access to these options for a variety of reasons. A simple technique to preoperatively plan for safe transiliac-transsacral screws is proposed. PMID- 27661734 TI - Bovine herpesvirus type-1 glycoprotein K (gK) interacts with UL20 and is required for infectious virus production. AB - We have previously shown that the HSV-1 gK and UL20 proteins interact and function in virion envelopment, membrane fusion, and neuronal entry. Alignment of the predicted secondary structures of gKs encoded by BoHV-1, HSV-1, HSV-2, EHV-1 and VZV indicated a high degree of domain conservation. Two BoHV-1 gK-null mutant viruses were created by either gK gene deletion or stop codon insertion. In addition, a V5 epitope-tag was inserted at the carboxyl terminus of gK gene to detect gK. The engineered gK-null mutant viruses failed to replicate and produce viral plaques. Co-immunoprecipitation of gK and UL20 expressed via different methods revealed that gK and UL20 physically interacted in the presence or absence of other viral proteins. Confocal microscopy showed that gK and UL20 colocalized in infected cells. These results indicate that BoHV-1 gK and UL20 may function in a similar manner to other alphaherpesvirus orthologues specified by HSV-1, PRV and EHV-1. PMID- 27661736 TI - Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6. AB - Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6 expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. PMID- 27661737 TI - Including health insurance in poverty measurement: The impact of Massachusetts health reform on poverty. AB - We develop and implement what we believe is the first conceptually valid health inclusive poverty measure (HIPM) - a measure that includes health care or insurance in the poverty needs threshold and health insurance benefits in family resources - and we discuss its limitations. Building on the Census Bureau's Supplemental Poverty Measure, we construct a pilot HIPM for the under-65 population under ACA-like health reform in Massachusetts. This pilot demonstrates the practicality, face validity and value of a HIPM. Results suggest that public health insurance benefits and premium subsidies accounted for a substantial, one third reduction in the health inclusive poverty rate. PMID- 27661735 TI - New influenza A(H7N7) viruses detected in live poultry markets in China. AB - H7N7 avian influenza viruses have been widely detected in wild birds and domestic poultry since they were first detected in chickens in Italy in 1902. They can occasionally transmit to humans. Here, we isolated six H7N7 viruses in live poultry markets during routine surveillance from 2010 to 2013. Sequences analysis revealed that these viruses are reassortants bearing genes of H3N8, H7N3, H7N7, and H10N7 influenza viruses detected in wild birds and ducks, and can be categorized into three genotypes (A, B, and C). All six viruses bound to both human-type and avian-type receptors. The viruses in genotype B and C could replicate efficiently in the lungs and nasal turbinates of mice without prior adaptation, and the genotype C virus also replicated in the brain of two of three mice tested. It is important to continue to monitor the evolution of H7N7 viruses and to evaluate their potential to cause human infections. PMID- 27661738 TI - Do hospital-owned skilled nursing facilities provide better post-acute care quality? AB - As hospitals are increasingly held accountable for patients' post-discharge outcomes under new payment models, hospitals may choose to acquire skilled nursing facilities (SNFs) to better manage these outcomes. This raises the question of whether patients discharged to hospital-based SNFs have better outcomes. In unadjusted comparisons, hospital-based SNF patients have much lower Medicare utilization in the 180 days following discharge relative to freestanding SNF patients. We solved the problem of differential selection into hospital-based and freestanding SNFs by using differential distance from home to the nearest hospital with a SNF relative to the distance from home to the nearest hospital without a SNF as an instrument. We found that hospital-based SNF patients spent roughly 5 more days in the community and 6 fewer days in the SNF in the 180 days following their original hospital discharge with no significant effect on mortality or hospital readmission. PMID- 27661740 TI - Introduction to Photonumeric Scales Issue. PMID- 27661739 TI - Eliminating composite bias in treatment effects estimates: Applications to quality of life assessment. AB - Researchers are often interested in composite measures such as overall ratings, indices of physical or mental health, or health-related quality-of-life (HRQoL) outcomes. Such measures are typically composed of two or more underlying discrete variables. In this paper, I investigate conditions where the estimated treatment effect based solely on the composite outcome is biased under non-random treatment assignment, which I refer to as composite bias. I then compare the magnitude of this bias across a variety of estimators, including ordinary least squares, propensity score estimators, and an alternative two-stage approach that first estimates treatment effects on the underlying outcomes and then combines these effects into an overall effect on the composite outcome of interest. The results highlight the presence of composite bias, identify general conditions under which such bias exists, and offer guidance as to how best to minimize this bias in practice. PMID- 27661741 TI - Development and Validation of a Photonumeric Scale for Evaluation of Volume Deficit of the Hand. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of hand appearance before and after treatment in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5 point photonumeric Allergan Hand Volume Deficit Scale. METHODS: The scale was developed to include an assessment guide, verbal descriptors, morphed images, and real-subject images for each grade. The clinical significance of a 1-point score difference was evaluated in a review of image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 296) completed during 2 sessions occurring 3 weeks apart. RESULTS: A score difference of >=1 point was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 1.12 [0.99-1.26] for clinically different image pairs and 0.45 [0.33 0.57] for not clinically different pairs). Intrarater agreement between the 2 validation sessions was almost perfect (mean weighted kappa = 0.83). Interrater agreement was almost perfect during the second session (0.82, primary end point). CONCLUSION: The Allergan Hand Volume Deficit Scale is a validated and reliable scale for physician rating of hand volume deficit. PMID- 27661742 TI - Development and Validation of a Photonumeric Scale for Evaluation of Volume Deficit of the Temple. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of temple appearance before and after aesthetic treatment in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5-point photonumeric Allergan Temple Hollowing Scale. METHODS: The scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each grade. The clinical significance of a 1-point score difference was evaluated in a review of image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 298) completed during 2 sessions occurring 3 weeks apart. RESULTS: A score difference of >=1 point was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 1.1 [0.94-1.26] for clinically different image pairs and 0.67 [0.51 0.83] for not clinically different pairs). Intrarater agreement between the 2 validation sessions was almost perfect (mean weighted kappa = 0.86). Interrater agreement was almost perfect during the second session (0.81, primary endpoint). CONCLUSION: The Allergan Temple Hollowing Scale is a validated and reliable scale for physician rating of temple volume deficit. PMID- 27661743 TI - Development and Validation of a Photonumeric Scale for Assessment of Chin Retrusion. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of chin appearance before and after chin augmentation in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5 point photonumeric Allergan Chin Retrusion Scale. METHODS: The Allergan Chin Retrusion Scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each scale grade. The clinical significance of a 1-point score difference was evaluated in a review of multiple image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 298) completed during 2 sessions occurring 3 weeks apart. RESULTS: A difference of >=1 point on the scale was shown to reflect a clinically meaningful difference (mean [95% confidence interval] absolute score difference, 1.07 [0.94-1.20] for clinically different image pairs and 0.51 [0.39-0.63] for not clinically different pairs). Intrarater agreement between the 2 live-subject validation sessions was substantial (mean weighted kappa = 0.79). Interrater agreement was substantial during the second rating session (0.68, primary end point). CONCLUSION: The Allergan Chin Retrusion Scale is a validated and reliable scale for physician rating of severity of chin retrusion. PMID- 27661744 TI - Development and Validation of a Photonumeric Scale for Evaluation of Facial Skin Texture. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of facial skin roughness before and after aesthetic treatment in practice and in clinical studies. OBJECTIVE: To describe the development and validation of the 5-point photonumeric Allergan Skin Roughness Scale. METHODS: The scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each grade. The clinical significance of a 1-point score difference was evaluated in a review of image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 290) completed during 2 sessions occurring 3 weeks apart. RESULTS: A score difference of >=1 point was shown to reflect a clinically meaningful difference (mean [95% confidence interval] absolute score difference 1.09 [0.96-1.23] for clinically different image pairs and 0.53 [0.38-0.67] for not clinically different pairs). Intrarater agreement between the 2 validation sessions was almost perfect (weighted kappa = 0.83). Interrater agreement was almost perfect during the second rating session (0.81, primary end point). CONCLUSION: The Allergan Skin Roughness Scale is a validated and reliable scale for physician rating of midface skin roughness. PMID- 27661745 TI - Development and Validation of a Photonumeric Scale for Evaluation of Facial Fine Lines. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of facial fine lines before and after treatment in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5 point photonumeric Allergan Fine Lines Scale. METHODS: The Allergan Fine Lines Scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each scale grade. The clinical significance of a 1-point score difference was evaluated in a review of multiple image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live subject validation study (N = 289) completed during 2 sessions occurring 3 weeks apart. RESULTS: A score difference of >=1 point was shown to reflect a clinically significant difference (mean [95% CI] absolute score difference, 1.06 [0.92-1.21] for clinically different image pairs and 0.50 [0.38-0.61] for not clinically different pairs). Intrarater agreement between the 2 live subject validation sessions was almost perfect (weighted kappa = 0.85). Interrater agreement was substantial during the second rating session (0.76, primary end point). CONCLUSION: The Allergan Fine Lines Scale is a validated and reliable scale for physician rating of severity of superficial fine lines. PMID- 27661746 TI - Development and Validation of a Photonumeric Scale for Evaluation of Transverse Neck Lines. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of horizontal neck lines before and after treatment in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5 point photonumeric Allergan Transverse Neck Lines Scale. METHODS: The Allergan Transverse Neck Lines Scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each scale grade. The clinical significance of a 1-point score difference was evaluated in a review of multiple image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject rating validation study (N = 297) completed during 2 sessions occurring 3 weeks apart. RESULTS: A difference of >=1 point on the scale was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 1.22 [1.09 1.35] for clinically different image pairs and 0.57 [0.42-0.72] for not clinically different pairs). Intrarater agreement between the 2 live-subject rating validation sessions was substantial (mean weighted kappa = 0.78). Interrater agreement was substantial during the second rating session (0.73, primary end point). CONCLUSION: The Allergan Transverse Neck Lines Scale is a validated and reliable scale for rating of severity of neck lines. PMID- 27661748 TI - Development and Validation of a Photonumeric Scale for Evaluation of Infraorbital Hollows. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of infraorbital hollows (i.e., tear troughs) before and after treatment in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5-point photonumeric Allergan Infraorbital Hollows Scale. METHODS: The scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each grade. The clinical significance of a 1-point score difference was evaluated in a review of image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 297) completed during 2 sessions occurring 3 weeks apart. RESULTS: A score difference of >=1 point was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 0.90 [0.79-1.02] for clinically different image pairs and 0.33 [0.19-0.46] for not clinically different pairs). Intrarater agreement between the 2 validation sessions was substantial (mean weighted kappa = 0.79). Interrater agreement was substantial during the second rating session (0.70, primary end point). CONCLUSION: The Allergan Infraorbital Hollows Scale is a validated and reliable scale for physician rating severity of hollowing in the infraorbital area. PMID- 27661747 TI - Development and Validation of a Photonumeric Scale for Evaluation of Static Horizontal Forehead Lines. AB - BACKGROUND: A validated scale is needed for objective and reproducible comparisons of static forehead lines before and after treatment in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5 point photonumeric Allergan Forehead Lines Scale. METHODS: The Allergan Forehead Lines Scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each scale grade. The clinical significance of a 1-point score difference was evaluated in a review of multiple image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 295) completed during 2 sessions occurring 3 weeks apart. RESULTS: A difference of >=1 point on the scale was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 1.06 [0.91-1.21] for clinically different image pairs and 0.38 [0.26-0.51] for not clinically different pairs). Intrarater agreement between the 2 live-subject validation sessions was almost perfect (mean weighted kappa = 0.87). Interrater agreement was almost perfect during the second rating session (0.86, primary end point). CONCLUSION: The Allergan Forehead Lines Scale is a validated and reliable scale for physician rating of static horizontal forehead lines. PMID- 27661749 TI - Pharmacotherapy of Obsessive-Compulsive Disorder During Breastfeeding. PMID- 27661750 TI - Promoting the Awareness of Hepatitis B Virus Screening in Patients With Lymphoma. PMID- 27661751 TI - Vitamin D: Use or Abuse in Older Adults? PMID- 27661752 TI - Octreotide-Induced Hypothermia-A Unique Occurrence. PMID- 27661753 TI - A Unique Presentation of Serum Sickness From Rabbit Antithymocyte Globulin in a Kidney Transplant Recipient. PMID- 27661754 TI - Hepatocellular Carcinoma With Budd-Chiari Syndrome and Obstructive Jaundice: A Therapeutic Challenge. PMID- 27661756 TI - Competition between "Meta Effect" Photochemical Reactions of Selected Benzophenone Compounds Having Two Different Substituents at Meta Positions. AB - Recent studies conducted on some "meta effect" photochemical reactions focused on aromatic carbonyls having a substitution on one meta position of the benzophenone (BP) and anthraquinone parent compound. In this paper, two different substitutions were introduced with one at each meta position of the BP parent compound to investigate possible competition between different types of meta effect photochemistry observed in acidic solutions containing water. The photochemical pathways of 3-hydroxymethyl-3'-fluorobenzophenone (1) and 3-fluoro 3'-methylbenzophenone (2) were explored in several solvents, including acidic water-containing solutions, using time-resolved spectroscopic experiments and density functional theory computations. It is observed that 1 can undergo a photoredox reaction and 2 can undergo a meta-methyl deprotonation reaction in acidic water-containing solutions. Comparison of these results to those previously reported for the analogous BP derivatives that contain only one substituent at a meta position indicates the introduction of electron-donating (such as hydroxyl) and electron-withdrawing groups (such as F) on the meta positions of BP can influence the meta effect photochemical reactions. It was found that involvement of an electron-donating moiety facilitates the meta effect photochemical reactions by stabilizing the crucial reactive biradical intermediate associated with the meta effect photochemical reactions. PMID- 27661755 TI - Surrogate alcohol containing methanol, social deprivation and public health in Novosibirsk, Russia. AB - Surrogate alcohol, i.e. alcohol not intended or not officially intended for human consumption, continues to play an important role in alcohol consumption in Russia, especially for people with alcohol dependence. Among the different types of surrogate alcohol, there are windshield washer antifreeze liquids; these products are the cheapest kinds of non-beverage alcohol available and thus likely to be used by the most deprived and marginalised groups such as homeless people with alcohol dependence. Although it is well known, that non-beverage alcohol is used for consumption by various groups in Russia, and although there are laws to prohibit the use of methanol as part of windshield washer antifreeze liquids for the very reason that such products could be used as surrogate alcohol, we detected products in retail sale which were a mix of water and methanol only. Methanol poses serious health threats including blindness and death, and there had been repeated methanol deaths from surrogate alcohol in Russia over the last years. If law-enforcement does not change for surrogate products, we can expect more methanol-resulting deaths in the most deprived and marginalized groups of people with alcohol dependence in Russia. In addition, ingredients with questionable safety profiles such as formic acid should also be prohibited in non beverage alcohol products that are likely to be consumed as surrogate alcohol. PMID- 27661757 TI - Sepsis-induced acute kidney injury. AB - PURPOSE OF REVIEW: Sepsis is a common and frequently fatal condition in which mortality has been consistently linked to increasing organ dysfunction. For example, acute kidney injury (AKI) occurs in 40-50% of septic patients and increases mortality six to eight-fold. However, the mechanisms by which sepsis causes organ dysfunction are not well understood and hence current therapy remains reactive and nonspecific. RECENT FINDINGS: Recent studies have challenged the previous notion that organ dysfunction is solely secondary to hypoperfusion, by showing, for example, that AKI occurs in the setting of normal or increased renal blood flow; and that it is characterized not by acute tubular necrosis or apoptosis, but rather by heterogeneous areas of colocalized sluggish peritubular blood flow and tubular epithelial cell oxidative stress. Evidence has also shown that microvascular dysfunction, inflammation, and the metabolic response to inflammatory injury are fundamental pathophysiologic mechanisms that may explain the development of sepsis-induced AKI. SUMMARY: The implications of these findings are significant because in the context of decades of negative clinical trials in the field, the recognition that other mechanisms are at play opens the possibility to better understand the processes of injury and repair, and provides an invaluable opportunity to design mechanism-targeted therapeutic interventions. PMID- 27661758 TI - In vitro DNA binding profile of enantiomeric dinuclear Cu(II)/Ni(II) complexes derived from l-/d-histidine-terepthaldehyde reduced Schiff base as potential chemotherapeutic agents. AB - New chiral reduced Schiff base ligands, L1 and L2 derived from l-/d-histidine and terepthaldehyde, and their Cu(II) and Ni(II) dinuclear complexes 1 &2 (a and b) were synthesized and thoroughly characterized by various spectroscopic techniques. Comparative binding profile of both l-/d-enantiomeric Cu(II) and Ni(II) complexes with ct-DNA was studied by employing optical and spectroscopic techniques to evaluate their enantiopreferential selectivity towards molecular target DNA and thereby explore their relative chemotherapeutic potential. Quantitative assessment of DNA binding propensity was ascertained by calculating Kb, K and Ksv values of 1 &2 (a and b) which demonstrated higher binding affinity of l-enantiomeric Cu(II) complex, 1a and followed the order as 1a>1b>2a>2b. Scanning electron microscopy (SEM) was used to analyze the morphological changes of the DNA condensate in presence of complexes 1 (a and b). The SEM micrographs condensates revealed morphological transitions and formation of different structural features implicating the condensation process between the complexes and biomolecule occurred to form compact massive structures. The gel electrophoretic assay of complex 1a was carried out with pBR322 plasmid DNA which revealed an efficient cleaving ability of the complex via oxidative pathway with the involvement of singlet oxygen (1O2) and the superoxide anion (O2*-) radicals as the ROS responsible the cleavage reactions. Molecular docking studies of 1 (a and b) with DNA revealed selective recognition of G-C residues of the narrow minor groove of the DNA duplex and complex 1a demonstrated binding affinity towards DNA ascertained from its higher binding energy values. Furthermore, the cytotoxic assessment of 1a was examined on a panel of cancer cell lines of different histological origin employing SRB assay which revealed remarkably good cytotoxic activity towards HL60, HeLa and MCF7 cancer cell lines. PMID- 27661759 TI - Low-level laser therapy (904nm) can increase collagen and reduce oxidative and nitrosative stress in diabetic wounded mouse skin. AB - BACKGROUND AND OBJECTIVE: Over the last decade we have seen an increased interest in the use of Low-Level Laser Therapy (LLLT) in diseases that involve increased oxidative stress. It is well established that hyperglycemia in diabetes elicits a rise in reactive oxygen species (ROS) production but the effect of LLLT remains unclear. This study aimed to investigate whether LLLT was able to improve oxidative/nitrosative stress parameters in the wound healing process in diabetic mice. STUDY DESIGN/MATERIALS AND METHODS: Twenty male mice were divided into four groups: non-irradiated control (NIC), irradiated control (IC), non-irradiated and diabetic (NID), irradiated and diabetic (ID). Diabetes was induced by administration of streptozotocin. Wounds were created 120days after the induction of diabetes in groups IC and ID and these groups were irradiated daily for 5days (superpulsed 904nm laser, average power 40mW, 60s). All animals were sacrificed 1day after the last irradiation and histology, collagen amount, catalase activity, nitrite and thiobarbituric acid reactive substances (TBARS) were measured. RESULTS: Histology showed that collagen fibers were more organized in IC and ID when compared to NID group, and significant differences in collagen content were found in group ID versus NID. Catalase activity was higher in IC group compared to other groups (p<0.001). TBARS levels were higher in IC versus NIC, but were lower in ID versus NID (p<0.001). Nitrite was lower in both irradiated groups versus the respective non-irradiated groups (p<0.001). CONCLUSIONS: Delayed wound healing in diabetes is still a challenge in clinical practice with high social costs. The increased production of collagen and decreased oxidative and nitrosative stress suggests that LLLT may be a viable therapeutic alternative in diabetic wound healing. PMID- 27661761 TI - Fluorescent Probes for Sensing and Imaging within Specific Cellular Organelles. AB - Fluorescent probes have become powerful tools in biosensing and bioimaging because of their high sensitivity, specificity, fast response, and technical simplicity. In the last decades, researchers have made remarkable progress in developing fluorescent probes that respond to changes in microenvironments (e.g., pH, viscosity, and polarity) or quantities of biomolecules of interest (e.g., ions, reactive oxygen species, and enzymes). All of these analytes are specialized to carry out vital functions and are linked to serious disorders in distinct subcellular organelles. Each of these organelles plays a specific and indispensable role in cellular processes. For example, the nucleus regulates gene expression, mitochondria are responsible for aerobic metabolism, and lysosomes digest macromolecules for cell recycling. A certain organelle requires specific biological species and the appropriate microenvironment to perform its cellular functions, while breakdown of the homeostasis of biomolecules or microenvironmental mutations leads to organelle malfunctions, which further cause disorders or diseases. Fluorescent probes that can be targeted to both specific organelles and biochemicals/microenvironmental factors are capable of reporting localized bioinformation and are potentially useful for gaining insight into the contributions of analytes to both healthy and diseased states. In this Account, we review our recent work on the development of fluorescent probes for sensing and imaging within specific organelles. We present an overview of the design, photophysical properties, and biological applications of the probes, which can localize to mitochondria, lysosomes, the nucleus, the Golgi apparatus, and the endoplasmic reticulum. Although a diversity of organelle-specific fluorescent stains have been commercially available, our efforts place an emphasis on improvements in terms of low cytotoxicity, high photostability, near-infrared (NIR) emission, two-photon excitation, and long fluorescence lifetimes, which are crucial for long-time tracking of biological processes, tissue and body imaging with deep penetration and low autofluorescence, and time-resolved fluorescence imaging. Research on fluorescent probes with both analyte responsiveness and organelle targetability is a new and emerging area that has attracted increasing attention over the past few years. We have extended the diversity by developing organelle-specific responsive probes capable of detecting changes in biomolecular levels (reactive oxygen species, fluoride ion, hydrogen sulfide, zinc cation, thiol-containing amino acids, and cyclooxygenase-2) and the microenvironment (viscosity, polarity, and pH). Future research should give more considerations of the "low-concern" organelles, such as the Golgi apparatus, the endoplasmic reticulum, and ribosomes. In addition, given the tiny sizes of subcellular organelles (20-1000 nm), we anticipate that clearer visulization of the cellular events within specific organelles will rely on super-resolution optical microscopy with nanoscopic-scale resolution. PMID- 27661760 TI - Capacitance of Nanoporous Carbon-Based Supercapacitors Is a Trade-Off between the Concentration and the Separability of the Ions. AB - Nanoporous carbon-based supercapacitors store electricity through adsorption of ions from the electrolyte at the surface of the electrodes. Room temperature ionic liquids, which show the largest ion concentrations among organic liquid electrolytes, should in principle yield larger capacitances. Here, we show by using electrochemical measurements that the capacitance is not significantly affected when switching from a pure ionic liquid to a conventional organic electrolyte using the same ionic species. By performing additional molecular dynamics simulations, we interpret this result as an increasing difficulty of separating ions of opposite charges when they are more concentrated, that is, in the absence of a solvent that screens the Coulombic interactions. The charging mechanism consistently changes with ion concentration, switching from counterion adsorption in the diluted organic electrolyte to ion exchange in the pure ionic liquid. Contrarily to the capacitance, in-pore diffusion coefficients largely depend on the composition, with a noticeable slowing of the dynamics in the pure ionic liquid. PMID- 27661762 TI - Electrophilic Fluorination of Secondary Phosphine Oxides and Its Application to P O Bond Construction. AB - A novel and efficient electrophilic fluorination of secondary phosphine oxides with Selectfluor has been achieved. This transformation provides direct access to phosphoric fluorides in up to 92% yield under mild conditions. In addition, P-O bond construction via a one-pot coupling process of secondary phosphine oxides with water or alcohols in the presence of Selectfluor leads to the formation of phosphinic acids or phosphinates in up to 96% yield. PMID- 27661763 TI - Electronic Communication in Closely Connected BODIPY-Based Bichromophores. AB - A small series of closely spaced, bichromophoric boron dipyrromethene (BODIPY) derivatives has been examined by optical spectroscopy and compared to the corresponding mononuclear dyes. The compounds vary according to the site of attachment and also by the nature of alkyl or aryl substituents incorporated into the dipyrrin backbone. Excitonic coupling splits the lowest-energy absorption transition in each case, but to highly variable degrees. There are also marked changes in the fluorescence quantum yields across the series but much less variation in the excited-state lifetimes. After comparing different models, it is concluded that the ideal dipole approximation gives a crude qualitative representation of the observed splitting of the absorption transition, but the extended dipole approach is not applicable to these systems. Agreement is substantially improved by employing a model that takes into account the dihedral angle between the planes of the two dipyrrin units. The large variation in radiative rate constants, and those for the accompanying nonradiative processes, is accountable in terms of electronic coupling and/or intensity borrowing between the two excitonic states. In all cases, the dihedral angle between the two BODIPY units plays a key role. PMID- 27661764 TI - Plasmonic Crystals for Strong Light-Matter Coupling in Carbon Nanotubes. AB - Their high oscillator strength and large exciton binding energies make single walled carbon nanotubes (SWCNTs) highly promising materials for the investigation of strong light-matter interactions in the near infrared and at room temperature. To explore their full potential, high-quality cavities-possibly with nanoscale field localization-are required. Here, we demonstrate the room temperature formation of plasmon-exciton polaritons in monochiral (6,5) SWCNTs coupled to the subdiffraction nanocavities of a plasmonic crystal created by a periodic gold nanodisk array. The interaction strength is easily tuned by the number of SWCNTs that collectively couple to the plasmonic crystal. Angle- and polarization resolved reflectivity and photoluminescence measurements combined with the coupled-oscillator model confirm strong coupling (coupling strength ~120 meV). The combination of plasmon-exciton polaritons with the exceptional charge transport properties of SWCNTs should enable practical polariton devices at room temperature and at telecommunication wavelengths. PMID- 27661765 TI - Band Alignment for Rectification and Tunneling Effects in Al2O3 Atomic-Layer Deposited on Back Contact for CdTe Solar Cell. AB - The present work intends to explain why ultrathin Al2O3 atomic-layer-deposited (ALD) on the back contact with rectification and tunneling effects can significantly improve the performance of CdTe solar cells in our previous work [ Liang , J. ; et al. Appl. Phys. Lett. 2015 , 107 , 013907 ]. Herein, we further study the mechanism through establishing the interfacial energy band diagram configuration of the ALD Al2O3/CuxTe by experiment of X-ray photoelectron spectroscopy and first-principles calculations and conclude to find the band alignment with optimized layer thickness (about 1 nm ALD Al2O3) as the key factor for rectification and tunneling effects. PMID- 27661766 TI - Decreased Level of Klotho Contributes to Drug Resistance in Lung Cancer Cells: Involving in Klotho-Mediated Cell Autophagy. AB - Klotho is originally discovered as an anti-aging gene and recently identified as a tumor suppressor in various human cancers. Drug resistance is a major obstacle to affect the treatment of chemotherapy. In the present study, we explore the role of klotho on drug resistance in human lung cancers and investigate the mechanism of klotho on drug resistance in lung cancer cells. First, we detected a panel of six human lung cancer cell lines, including H460, SK-MES-1, cisplatin (DDP)-resistant A549/DDP, its parental subline A549, docetaxel (DTX)-resistant SPC-A-1/DTX, and SPC-A-1 by western blotting analysis. The results showed that klotho level was significantly decreased in chemotherapeutic drug-resistant lung cancer cells. Next, klotho was overexpressed in drug-resistant cancer cell lines and the results showed that overexpression of klotho significantly inhibited cell proliferation of A549/DDP and SPC-A-1/DTX. Conversely, knockdown of the expression of klotho significantly promoted cell growth of lung cancer cells. Furthermore, overexpression of klotho had synergistic effects with cisplatin to inhibit the proliferation of drug-resistant lung cancer cells in a dose- and time dependent manner. The molecular mechanism was explored by western blotting analysis and the results revealed that the levels of beclin 1 and LC3-II were obviously increased, suggesting cell autophagy enhanced in drug-resistant cancer cells. Importantly, overexpression of klotho would inhibit cell autophagy in A549/DDP cells. All the results demonstrated that the levels of klotho were significantly decreased, which was accompanied by the increased cell autophagy in drug-resistant lung cancer cells. Overexpression of klotho would inhibit cell autophagy in drug-resistant lung cancers, which may probably contribute to reverse drug resistance in lung cancer cells. PMID- 27661767 TI - Comparison of the effects of four different cochlear implant electrodes on intra cochlear pressure in a model. AB - CONCLUSION: Based on this model experiment, a small tip and low volume electrode show lowest intra-cochlear pressure values. Insertional support by a tool minimizes fast pressure changes. Higher electrodes volumes affect slow and fast pressure changes as well. OBJECTIVE: Insertion causing low intra-cochlear pressure is assumed to be important for atraumatic cochlear implant surgery to preserve residual hearing. Cochlear implant electrodes differ in terms of parameters like tip size, length, volume, and technique of insertion. The aim of this study was to observe the effect of different cochlear implant electrodes on insertional intra-cochlear pressure in a cochlear model. MATERIALS AND METHODS: Cochlear implant electrode insertions were performed in an artificial cochlear model and intra-cochlear pressure changes were recorded in parallel with a micro pressure sensor positioned in the apical region of the cochlear model to follow the maximum values, temporal changes, maximum amplitude, and frequency of changes in intra-cochlear pressure. Insertions were performed with four different electrodes (Advanced Bionics 1j, Helix, HFMS, and LW23). RESULTS: This study found statistically significant differences in the occurrence of initial maximum pressure values correlating with the electrode tip size. The different electrodes and the technique of insertion significantly affected the occurrence of maximum value, amplitude, and frequency of intra-cochlear pressure occurrence. PMID- 27661768 TI - Detecting tumor progression in glioma: current standards and new techniques. AB - INTRODUCTION: The post-treatment monitoring of glioma patients remains an area of active research and development. Conventional imaging with MRI is a highly sensitive modality for detecting and monitoring primary and secondary brain tumors and includes multi-parametric sequences to better characterize the disease. Standardized schemes for measuring response to treatment are in wide clinical use; however, the introduction of new therapeutics have introduced new patterns of response that can confound interpretation of conventional MRI and can cause uncertainty in the proper management following therapy. Areas covered: A summary of current and evolving techniques for assessing glioma response in this era of new therapies that address these challenges are presented in this review. While this review focuses more on clinical and early clinical methodologies for MRI and nuclear medicine techniques some promising pre-clinical techniques are also presented. Expert commentary: While successful single institution results have been widely reported in the literature, any new methodologies must be undertaken in multi-center settings. Additionally, the need for standardization of protocols in quantitative measured are an important area that must be addressed for new and promising techniques to be implemented to a wide array of patients. PMID- 27661769 TI - A qualitative description of successful aging through different decades of older adulthood. AB - OBJECTIVE: To qualitatively examine factors that contribute to successful aging during different decades of older adulthood. METHODS: Fundamental qualitative description was adopted as the methodological framework. Through purposeful sampling, 42 community dwelling older adults (mean age = 79.6 years, age range = 65-97 years; 19 males) were recruited. Focus groups (6) segmented by decade of life were conducted with participants 65-74 (n = 17) and 75-84 (n = 17) years of age. Semi-structured interviews (16) were conducted with four participants from each decade, as well as participants 85 years of age and older (n = 8). Data analyses were conducted independently for each decade of life and included inductive analysis of textual data through continuous comparisons of meaning units. RESULTS: Three primary themes related to successful aging were identified across all decades of older adulthood: (1) staying healthy (secondary themes: genetics and lifestyle choices), (2) maintaining an active engagement in life (secondary themes: social engagement and cognitive engagement), and (3) keeping a positive outlook on life. Participants in specific decades of older adulthood identified three additional secondary themes related to maintaining an active engagement in life: finances (65-74 and 85+ years), social support (75+ years), and successful marriage (75+ years). Similarly, only adults 65-84 years of age identified a secondary theme for keeping a positive outlook on life: acceptance and adaptation. CONCLUSION: Primary themes related to successful aging were agreed upon by participants in all decades of older adulthood, while age-based differences existed among secondary themes. Thus, what it means to age successfully may be age-dependent. PMID- 27661770 TI - Identification of chemical ingredients of peanut stems and leaves extracts using UPLC-QTOF-MS coupled with novel informatics UNIFI platform. AB - Peanut stems and leaves have been used traditionally as both herbal medicines and special food in Asia. In this study, the main functional compounds of peanut stems and leaves extracts were identified using UPLC separation coupled to high resolution mass spectrometry (QTOF-MS), and a traditional medicine library. Three different extraction solvents (ethyl acetate, petroleum ether and n-butanol) were evaluated to prepare the extracts of peanut stems and leaves. A total of 283 chemical compounds were identified in peanut stems and leaves extracts, of which 207 compounds are tentatively new identifications in Genus Arachis. The integration of data acquisition and processing with the traditional medicine library provides a simple, efficient process to effectively facilitate the identification of chemical ingredients in complex natural product extracts. The integrated workflow for separation, detection and identification of functional compounds in natural products using UPLC/QTOF-MS greatly improves productivity for development of traditional herbal medicines. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27661771 TI - Differential abilities of nitrogen dioxide and nitrite to nitrate proteins in thylakoid membranes isolated from Arabidopsis leaves. AB - Exposure of Arabidopsis leaves to nitrogen dioxide (NO2) results in nitration of specific chloroplast proteins. To determine whether NO2 itself and/or nitrite derived from NO2 can nitrate proteins, Arabidopsis thylakoid membranes were isolated and treated with NO2-bubbled or potassium nitrite (KNO2) buffer, followed by protein extraction, electrophoresis, and immunoblotting using an anti 3-nitrotyrosine (NT) antibody. NO2 concentrations in the NO2-bubbled buffer were calculated by numerically solving NO2 dissociation kinetic equations. The two buffers were adjusted to have identical nitrite concentrations. Both treatments yielded an NT-immunopositive band that LC/MS identified as PSBO1. The difference in the band intensity between the 2 treatments was designated nitration by NO2. Both NO2 and nitrite mediated nitration of proteins, and the nitration ability per unit NO2 concentration was ~100-fold greater than that of nitrite. PMID- 27661772 TI - pH and metal concentration of synovial fluid of osteoarthritic joints and joints with metal replacements. AB - BACKGROUND: Due to degradation and metal dissolution during articulation of metal joint replacements the chemical periprosthetic environment may change. The aim was to establish whether metal replacements cause the local changes in pH and elevated metal concentrations. METHODS: pH was measured on samples from 167 patients: native hip and knee osteoarthritic joints, joints with hip and knee replacements revised for aseptic or septic reasons. pH of synovial fluid and periprosthetic tissue was measured perioperatively using a microelectrode and pH indicator papers for removed metal components. Metal concentrations were measured in 21 samples using inductively coupled plasma mass spectrometry. RESULTS: The mean pH value of synovial fluid at native osteoarthritic joints (n = 101) was 7.78 +/- 0.38. The mean pH value of synovial fluid at revision aseptic operation (n = 58) was 7.60 +/- 0.31, with statistically significant difference (p = 0.002) compared to native osteoarthritic joints. The mean pH value of synovial fluid at revision septic operation (n = 8) was 7.55 +/- 0.25, with statistically significant difference (p = 0.038) compared to native osteoarthritic joints. Measurements in tissue and at stems were not reliable. In the majority of samples taken at revision increased levels of cobalt and chromium were measured. CONCLUSION: A small but statistically significant difference was observed in the pH of synovial fluid between natural joints with degenerative diseases and joints treated with metal replacements. Based on the increased metal levels we expected the value of pH to be lower, but the influence of metal ions is counteracted by the buffering capacity of human body. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2507-2515, 2017. PMID- 27661773 TI - Decarboxylative Aminomethylation of Aryl- and Vinylsulfonates through Combined Nickel- and Photoredox-Catalyzed Cross-Coupling. AB - A mild approach for the decarboxylative aminomethylation of aryl sulfonates by the combination of photoredox and nickel catalysis through C-O bond cleavage is described for the first time. A wide range of aryl triflates as well as aryl mesylates, tosylates and alkenyl triflates afford the corresponding products in good to excellent yields. PMID- 27661774 TI - Graded fear generalization enhances the level of cfos-positive neurons specifically in the basolateral amygdala. AB - Fear is an important emotional reaction in response to threatening stimuli and is important for survival. However, when fear occurs in inappropriate circumstances, it can lead to pathological conditions including an increased vulnerability for developing anxiety disorders such as posttraumatic stress disorder (PTSD). Patients with PTSD generalize fear to contexts or to environments that are not associated with the trauma. We sought to explore if increasing the level of dissimilarity relative to the context in which mice learn fear results in changes in the level of fear responding to the new context. We also determined with this procedure if the number of cells expressing the immediate early gene cfos changes with the corresponding level of expressed fear within brain regions known to be important in modulating fear, including the basolateral amygdala (BLA) and hippocampus. Our results indicate that mice that were tested in increasingly different contexts showed significantly different levels of fear responses. Freezing level was higher in the context most similar to the acquisition context than the one that was highly different. The level of cfos within the BLA, but not hippocampus, was also significantly different between the test contexts, with higher levels in the somewhat similar compared with the most different context. Overall, these results highlight the BLA as a critical region in the node of fear circuitry for modulating fear generalization. (c) 2016 Wiley Periodicals, Inc. PMID- 27661775 TI - Diagnostic performance of diffusion tensor imaging parameters in breast cancer and correlation with the prognostic factors. AB - PURPOSE: To evaluate the diagnostic performances of the diffusion tensor imaging (DTI) parameters in the diagnosis of breast cancer and to investigate the variations in DTI parameters according to the breast cancer biomarkers. MATERIALS AND METHODS: At 3.0 Tesla (T), DTI was performed in 85 patients with 92 enhancing breast lesions. lambda1 , lambda2 , lambda3 , mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy (FA), relative anisotropy (RA), and geodesic anisotropy (GA) were studied and compared with diffusion-weighted imaging-derived apparent diffusion coefficient. Lesions were analyzed according to BIRADS lexicon. Logistic regression models were constructed to determine the contribution of DTI to the specificity and the accuracy of DCE-MRI. Breast cancer biomarkers; estrogen receptor (ER), HER-2 status, and Ki-67 were correlated with DTI in malignant cases. RESULTS: Malignant lesions exhibited significantly lower MD, RD, lambda1 , lambda2 , lambda3 and higher FA, RA, GA values (P < 0.001). Logistic regression models showed that MD, RD, lambda1 , lambda2 , lambda3 , FA, and RA increase the specificity of the DCE-MRI (from 83.0% to 89.4-93.6%; P < 0.05). Higher RD, lambda2 , lambda3 and lower FA, RA, and GA values were observed in ER-negative breast cancer (P < 0.05). Ki-67 showed significant, negative correlation with FA, RA, GA, lambda1 -lambda3 and lambda1 -lambda2 (r = -0.336 to -0.435; P < 0.05). CONCLUSION: Besides its ability to differentiate malignant breast lesions, DTI improves the specificity of conventional 3.0T breast MRI and shows correlation with biomarkers ER and Ki-67. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:660-672. PMID- 27661776 TI - Hypoglycemia Enhances Epithelial-Mesenchymal Transition and Invasiveness, and Restrains the Warburg Phenotype, in Hypoxic HeLa Cell Cultures and Microspheroids. AB - The accelerated growth of solid tumors leads to episodes of both hypoxia and hypoglycemia (HH) affecting their intermediary metabolism, signal transduction, and transcriptional activity. A previous study showed that normoxia (20% O2 ) plus 24 h hypoglycemia (2.5 mM glucose) increased glycolytic flux whereas oxidative phosphorylation (OxPhos) was unchanged versus normoglycemia in HeLa cells. However, the simultaneous effect of HH on energy metabolism has not been yet examined. Therefore, the effect of hypoxia (0.1-1% O2 ) plus hypoglycemia on the energy metabolism of HeLa cells was analyzed by evaluating protein content and activity, along with fluxes of both glycolysis and OxPhos. Under hypoxia, in which cell growth ceased and OxPhos enzyme activities, DeltaPsim and flux were depressed, hypoglycemia did not stimulate glycolytic flux despite increasing H RAS, p-AMPK, GLUT1, GLUT3, and HKI levels, and further decreasing mitochondrial enzyme content. The impaired mitochondrial function in HH cells correlated with mitophagy activation. The depressed OxPhos and unchanged glycolysis pattern was also observed in quiescent cells from mature multicellular tumor spheroids, suggesting that these inner cell layers are similarly subjected to HH. The principal ATP supplier was glycolysis for HH 2D monolayer and 3D quiescent spheroid cells. Accordingly, the glycolytic inhibitors iodoacetate and gossypol were more effective than mitochondrial inhibitors in decreasing HH-cancer cell viability. Under HH, stem cell-, angiogenic-, and EMT-biomarkers, as well as glycoprotein-P content and invasiveness, were also enhanced. These observations indicate that HH cancer cells develop an attenuated Warburg and pronounced EMT- and invasive-phenotype. J. Cell. Physiol. 232: 1346-1359, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27661777 TI - Imaging far and wide. AB - A custom-built objective lens called the Mesolens allows relatively large biological specimens to be imaged with cellular resolution. PMID- 27661778 TI - A novel optical microscope for imaging large embryos and tissue volumes with sub cellular resolution throughout. AB - Current optical microscope objectives of low magnification have low numerical aperture and therefore have too little depth resolution and discrimination to perform well in confocal and nonlinear microscopy. This is a serious limitation in important areas, including the phenotypic screening of human genes in transgenic mice by study of embryos undergoing advanced organogenesis. We have built an optical lens system for 3D imaging of objects up to 6 mm wide and 3 mm thick with depth resolution of only a few microns instead of the tens of microns currently attained, allowing sub-cellular detail to be resolved throughout the volume. We present this lens, called the Mesolens, with performance data and images from biological specimens including confocal images of whole fixed and intact fluorescently-stained 12.5-day old mouse embryos. PMID- 27661779 TI - Selective Formation of Alkoxychlorosilanes and Organotrialkoxysilane with Four Different Substituents by Intermolecular Exchange Reaction. AB - Alkoxychlorosilanes are scientifically and industrially important toward preparing silicone and silica as well as preparation of siloxane-based nanomaterials by stepwise reactions of Si-OR (R=alkyl) and Si-Cl groups. Intermolecular exchange of alkoxy and chloro groups between alkoxysilanes and chlorosilanes (functional group exchange reaction) provides an efficient and environmentally benign route to alkoxychlorosilanes. BiCl3 as a Lewis acid catalyst can promote the functional group exchange reactions more efficiently than conventional acid catalysts. Higher reactivity has been observed for chlorosilanes with smaller numbers of Si-CH3 groups and for alkoxysilanes with larger numbers of Si-CH3 groups. The reaction mechanism is proposed and selective syntheses of alkoxychlorosilanes are demonstrated. These findings also enable us to synthesize an organotrialkoxysilane with four different substituents. PMID- 27661781 TI - Questioning the use of an age-adjusted D-dimer threshold to exclude venous thromboembolism: analysis of individual patient data from two diagnostic studies: reply. PMID- 27661782 TI - Does Medical Risk Perception and Risk Taking Change with Age? AB - Across adulthood, people face increasingly more risky medical problems and decisions. However, little is known about changes in medical risk taking across adulthood. Therefore, the current cross-sectional study investigated age-related differences in medical risk taking with N = 317 adults aged 20-77 years using newly developed scenarios to assess medical risk taking, and additional measures designed to evaluate risk-taking behavior in the medical domain. Greater expected benefits on the Domain-Specific Risk-Taking Scale-Medical (DOSPERT-M) predicted more active risk taking, whereas higher perceived risk predicted less active risk taking. Next, we examined differences in active and passive risk taking, where passive risk taking refers to risk taking that is associated with inaction. Age was associated with less passive risk taking, but not with active risk taking, risk perception, or expected benefits on the DOSPERT-M. Participants were overall more likely to opt for taking medical action than not, even more so for a scenario about a vaccine for a deadly flu than for a scenario about a chemotherapy treatment for cancer. Overall, participants were more likely to accept medication (vaccine or chemotherapy) for their child than for themselves. Increasing age was associated with a lower likelihood of accepting the treatment or vaccine for oneself. Taken together, our study provides important insights about changes in medical risk taking across adulthood when people face an increasing number of complex and risky medical decisions. PMID- 27661783 TI - Hypertension management in the oldest old: Findings from a large long-term care facility. AB - PURPOSE: The purpose of this quality improvement project was to evaluate hypertension (HTN) management in patients 80 years of age and older who reside in a large, long-term care (LTC) facility. DATA SOURCE: A retrospective chart audit was conducted on 75 charts of patients 80 years of age and older and who had a diagnosis of HTN. Using the 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Expert Consensus Document on Management of Hypertension in the Elderly as a guide, blood pressure readings, significant comorbidities, and antihypertensive medication utilization were analyzed. CONCLUSIONS: LTC residents in this sample were often not treated according to expert recommendations. Specifically, analysis revealed overtreatment of uncomplicated HTN and undertreatment of those with comorbid conditions. Additionally, those with diabetes mellitus and chronic kidney disease were infrequently prescribed ace inhibitors/angiotensin receptor blockers, as recommended. IMPLICATIONS FOR PRACTICE: Utilizing evidence-based practice (EBP) guidelines affords the best avenue for providing safe and effective treatment of HTN. While expert recommendations are available, researchers seldom recruit frail elders in LTC facilities into treatment investigations. In the absence of population-specific EBP guidelines, nurse practitioners must rely on expert opinion and diagnostic reasoning to individualize HTN treatment to this unique and vulnerable population. PMID- 27661780 TI - Using long-term experimental evolution to uncover the patterns and determinants of molecular evolution of an Escherichia coli natural isolate in the streptomycin treated mouse gut. AB - Although microbial ecology of the gut is now a major focus of interest, little is known about the molecular determinants of microbial adaptation in the gut. Experimental evolution coupled with whole-genome sequencing can provide insights of the adaptive process. In vitro experiments have revealed some conserved patterns: intermediate convergence, and epistatic interactions between beneficial mutations and mutations in global regulators. To test the relevance of these patterns and to identify the selective pressures acting in vivo, we have performed a long-term adaptation of an E. coli natural isolate, the streptomycin resistant strain 536, in the digestive tract of streptomycin-treated mice. After a year of evolution, a clone from 15 replicates was sequenced. Consistently with in vitro observations, the identified mutations revealed a strong pattern of convergence at the mutation, gene, operon and functional levels. Yet, the rate of molecular evolution was lower than in in vitro, and no mutations in global regulators were recovered. More specific targets were observed: the dgo operon, involved in the galactonate pathway that improved growth on D-galactonate, and rluD and gidB, implicated in the maturation of the ribosomes, which mutations improved growth only in the presence of streptomycin. As in vitro, the nonrandom associations of mutations within the same pathways suggested a role of epistasis in shaping the adaptive landscape. Overall, we show that 'evolve and sequence' approach coupled with an analysis of convergence, when applied to a natural isolate, can be used to study adaptation in vivo and uncover the specific selective pressures of that environment. PMID- 27661785 TI - Population structure and gene flow in the global pest, Helicoverpa armigera. AB - Helicoverpa armigera is a major agricultural pest that is distributed across Europe, Asia, Africa and Australasia. This species is hypothesized to have spread to the Americas 1.5 million years ago, founding a population that is at present, a distinct species, Helicoverpa zea. In 2013, H. armigera was confirmed to have re-entered South America via Brazil and subsequently spread. The source of the recent incursion is unknown and population structure in H. armigera is poorly resolved, but a basic understanding would highlight potential biosecurity failures and determine the recent evolutionary history of region-specific lineages. Here, we integrate several end points derived from high-throughput sequencing to assess gene flow in H. armigera and H. zea from populations across six continents. We first assemble mitochondrial genomes to demonstrate the phylogenetic relationship of H. armigera with other Heliothine species and the lack of distinction between populations. We subsequently use de novo genotyping by-sequencing and whole-genome sequences aligned to bacterial artificial chromosomes, to assess levels of admixture. Primarily, we find that Brazilian H. armigera are derived from diverse source populations, with strong signals of gene flow from European populations, as well as prevalent signals of Asian and African ancestry. We also demonstrate a potential field-caught hybrid between H. armigera and H. zea, and are able to provide genomic support for the presence of the H. armigera conferta subspecies in Australasia. While structure among the bulk of populations remains unresolved, we present distinctions that are pertinent to future investigations as well as to the biosecurity threat posed by H. armigera. PMID- 27661784 TI - An improved 19 F-CPMG scheme for detecting binding of polyfluorinated molecules to biological receptors. PMID- 27661786 TI - Determination of volatile polycyclic aromatic hydrocarbons in waters using headspace solid-phase microextraction with a benzyl-functionalized crosslinked polymeric ionic liquid coating. AB - A benzyl-functionalized crosslinked polymeric ionic liquid (PIL), produced through the co-polymerization of the 1-vinylbenzyl-3-hexadecylimidazolium bis[(trifluoromethyl)sulfonyl]imide (VBHDIM-NTf2) ionic liquid (IL) monomer and 1,12-di(3-vinylbenzylimidazolium)dodecane bis[(trifluoromethyl)sulfonyl]imide ((DVBIM)2C12-2NTf2) IL crosslinker, was successfully used as a sorbent coating in headspace solid-phase microextraction (SPME) coupled to gas chromatography (GC) with flame-ionization detection (FID) to determine seven volatile polycyclic aromatic hydrocarbons (PAHs) in environmental water samples. Optimum extraction conditions for the PAHs when using the novel sorbent include an extraction temperature of 50 degrees C, an ionic strength content adjusted with 30% (w/v) NaCl in the aqueous sample, and an extraction time of 60 min. The extraction performance of the crosslinked PIL fiber was compared to the SPME commercial coating polydimethylsiloxane fiber. The calibration ranges of the studied PAHs were linear in the range of 0.02-20 ug L-1 for the crosslinked PIL fiber. The accuracy of the proposed method was demonstrated by examining the spiked recoveries of seven PAHs which produced values ranging from 67.2% to 130% (for river- and seawater samples), and precision values lower than 9.4% for a spiked level of 1 ug L-1, and detection limits between 0.01 and 0.04 ug L-1, which supports the sensitivity of the method using GC-FID. PMID- 27661787 TI - Salvage therapy or simplification of salvage regimens with dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART-experienced subjects: an Italian cohort. AB - BACKGROUND: Dolutegravir plus darunavir provide a high genetic barrier to HIV-1 resistance and are suitable for simple salvage regimens. METHODS: All HIV-1 infected subjects treated with dolutegravir plus boosted darunavir dual therapy between March 2011 and September 2015 were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. RESULTS: We enrolled 113 subjects. After week 24, one was lost at follow-up, one dropped out for grade 2 elevation of liver enzymes, one died from illicit drug abuse and one from cancer-related sepsis. The mean age was 51, 26.5% were female and 9.7% were non-Caucasian. Twenty had never experienced failure. A total of 99 had reverse transcriptase (RT) mutations, 87 had protease inhibitor mutations and 12 had integrase strand transfer inhibitor (INSTI) mutations. Viraemic patients declined from baseline to week 24 from 43.4% to 6.2%, the remainder being due to high baseline viraemia or adherence issues. The proportion of subjects with viraemia 1 49 copies/ml remained at 20.4% while those in whom no virus was detected (NVD) increased from 36.3% to 73.5% by week 24. All the 47 subjects who had a 48-week follow-up had <50 copies/ml and 42 (89.4%) had NVD. 18 subjects had reduced sensitivity to darunavir (Stanford median score 15, range 15-40), but none rebounded, 6 having a 24-week and 7 a 48-week follow-up. The median variation in serum creatinine was -0.01 (range +0.2 to -0.21) mg/dl. CONCLUSIONS: This dual regimen provides a simple salvage regimen and proved safe and effective in this cohort. PMID- 27661788 TI - Patient-centered methadone treatment: a randomized clinical trial. AB - BACKGROUND AND AIMS: Methadone patients who discontinue treatment are at high risk of relapse, yet a substantial proportion discontinue treatment within the first year. We investigated whether a patient-centered approach to methadone treatment improved participant outcomes at 12 months following admission, compared with methadone treatment-as-usual. DESIGN: Two-arm open-label randomized trial. SETTING: Two methadone treatment programs (MTPs) in Baltimore, MD, USA. PARTICIPANTS: Three hundred newly admitted MTP patients were enrolled between 13 September 2011 and 26 March 2014. Their mean age was 42.7 years [standard deviation (SD) = 10.1] and 59% were males. INTERVENTION: Newly admitted MTP patients were assigned randomly to either patient-centered methadone treatment (PCM; n = 149), which modified the MTP's rules (e.g. counseling attendance was optional), and counselor roles (e.g. counselors were not responsible for enforcing clinic rules) or treatment-as-usual (TAU; n = 151). MEASUREMENTS: The primary outcome was opioid-positive urine test at 12-month follow-up. Other 12 month outcomes included days of heroin and cocaine use, cocaine-positive urine tests, meeting DSM-IV opioid and cocaine dependence diagnostic criteria, HIV risk behavior and quality of life and retention in treatment. FINDINGS: There was no significant difference between PCM and TAU conditions in opioid-positive urine screens at 12 months [adjusted odds ratio = 0.98; 95% confidence interval (CI) = 0.61, 1.56]. There were also no significant differences in any of the secondary outcome measures (all Ps > 0.05) except Quality of Life Global Score (P = 0.04; 95% CI = 0.01, 0.45). There were no significant differences between conditions in the number of individual or group counseling sessions attended. (Ps > 0.05). CONCLUSIONS: Patient-centered methadone treatment (with optional counseling and the counselor not serving as the treatment program disciplinarian) does not appear to be more effective than methadone treatment-as-usual. PMID- 27661789 TI - YEATS domain: Linking histone crotonylation to gene regulation. AB - Recent research reveals that the YEATS domains preferentially recognize crotonylated lysines on histones. Here, we discuss the molecular mechanisms that enable this recognition and the biological significances of this interaction. The dynamics of histone crotonylation and its potential roles in the regulation of gene expression will also be discussed. PMID- 27661790 TI - The Legal System and Alzheimer's Disease: Social Workers and Lawyers' Perceptions and Experiences. AB - The expected increase in the number of people living with Alzheimer's disease (AD) worldwide will be accompanied by an increase in the number of cases involving persons with AD brought up to the courts. This study examined the perceptions and experiences of social workers and lawyers regarding these cases. Three focus groups including social workers and lawyers (n = 26) were conducted. Two main themes were raised by the participants: (a) the role of social workers and lawyers in court cases regarding AD, and (b) the need for improving legal encounters involving persons with AD. Similarities and differences were found in both professionals' interpretations of these shared themes. Results of this study emphasize the need for increasing the knowledge and interprofessional training provided to social workers and lawyers involved in legal cases dealing with issues involving persons with Alzheimer's disease. PMID- 27661791 TI - Podocytic infolding glomerulopathy: A case report. AB - Podocytic infolding glomerulopathy (PIG) is a rare glomerular abnormality involving glomerular basement membrane (GBM) bubbling viewable by light microscopy, extensive invagination of the podocytic cytoplasm, and the presence of microstructures viewable by electron microscopy. PIG was proposed as a new disease entity in 2008. However, cases have been reported exclusively in Japan and no case reports outside Japan have been published. Here, we report a case of PIG in a 44-year-old Korean female. The patient showed mild proteinuria without renal functional impairment or other systemic diseases. Glomeruli were normocellular, but GBMs were diffusely and mildly thickened and showed a bubbly appearance with periodic acid methenamine silver (PAMS) staining. Immunofluorescence microscopy showed minimal mesangial IgM deposition, but staining was negative for IgG, IgA, C3, C4, C1q, and fibrinogen. Electron microscopy showed diffuse distribution of microtubules and microspherules within thickened GBM (620-1180 nm). Additional serologic tests revealed positive antinuclear antibodies, but other autoimmune markers were normal or negative. The patient was treated with steroids for three months, after which proteinuria decreased to the normal range. PMID- 27661793 TI - Community Health Workers: An Untapped Resource to Promote Genomic Literacy. AB - Poor understanding of gene-environment contributors to health conditions can lead the public to misinterpretations that overemphasize genetics as determinants of health. The present commentary calls for engaging the national community health worker (CHW) workforce to use community elicitation methods such as mental models approaches as a means to enhance the public's literacy regarding genetic and environmental or genomic contributions to health. We discuss three needs related to genomic literacy and suggest how CHWs are uniquely positioned to address these needs among diverse target audiences. We conclude by offering directions for the future of CHWs working to build genomic literacy. PMID- 27661792 TI - Spinal-Exercise Prescription in Sport: Classifying Physical Training and Rehabilitation by Intention and Outcome. AB - CONTEXT: Identification of strategies to prevent spinal injury, optimize rehabilitation, and enhance performance is a priority for practitioners. Different exercises produce different effects on neuromuscular performance. Clarity of the purpose of a prescribed exercise is central to a successful outcome. Spinal exercises need to be classified according to the objective of the exercise and planned physical outcome. OBJECTIVE: To define the modifiable spinal abilities that underpin optimal function during skilled athletic performance, clarify the effect of spinal pain and pathologic conditions, and classify spinal exercises according to the objective of the exercise and intended physical outcomes to inform training and rehabilitation. DESIGN: Qualitative study. DATA COLLECTION AND ANALYSIS: We conducted a qualitative consensus method of 4 iterative phases. An exploratory panel carried out an extended review of the English-language literature using CINAHL, EMBASE, MEDLINE, and PubMed to identify key themes and subthemes to inform the definitions of exercise categories, physical abilities, and physical outcomes. An expert project group reviewed panel findings. A draft classification was discussed with physiotherapists (n = 49) and international experts. Lead physiotherapy and strength and conditioning teams (n = 17) reviewed a revised classification. Consensus was defined as unanimous agreement. RESULTS: After the literature review and subsequent analysis, we defined spinal abilities in 4 categories: mobility, motor control, work capacity, and strength. Exercises were subclassified by functionality as nonfunctional or functional and by spinal displacement as either static (neutral spinal posture with no segmental displacement) or dynamic (dynamic segmental movement). The proposed terminology and classification support commonality of language for practitioners. CONCLUSIONS: The spinal-exercise classification will support clinical reasoning through a framework of spinal-exercise objectives that clearly define the nature of the exercise prescription required to deliver intended physical outcomes. PMID- 27661794 TI - Rivaroxaban significantly inhibits the stimulatory effects of bone-modulating hormones: In vitro study of primary female osteoblasts. AB - BACKGROUND: Anticoagulant therapy is a mainstay of treatment subsequent to major orthopedic surgeries. Evidence linking anticoagulant therapy, osteoporosis, and delayed fracture healing is not conclusive. We have previously reported that rivaroxaban significantly inhibited cell growth and energy metabolism in a human osteoblastic cell line. This study analyzed the response of primary female osteoblast cells to rivaroxaban in combination with various bone-modulating hormones. METHODS: Bone samples were taken from both premenopausal (pre-Ob) and postmenopausal (post-Ob) women. Cells were isolated from each sample and cultured to sub-confluence. Each sample was then treated with Rivaroxaban (10 ug/ml) in combination with the following hormones or with the hormones alone for 24 hours: 30nM estradiol-17beta (E2), 390nM estrogen receptor alpha (ERalpha) agonist PPT, 420nM estrogen receptor beta (ERbeta) agonist DPN, 50nM parathyroid hormone (PTH), and 1nM of vitamin D analog JKF. RESULTS: No effects were observed after exposure to rivaroxaban alone. When pre-Ob and post-Ob cells were exposed to the bone-modulating hormones as a control experiment, DNA synthesis and creatine kinase (CK)-specific activity was significantly stimulated with a greater response in the pre-Ob cells. When the cells were exposed to rivaroxaban in combination with bone-modulating hormones, the increased DNA synthesis and CK specific activity previously observed were completely attenuated. CONCLUSIONS: Rivaroxaban significantly inhibited the stimulatory effects of bone-modulating hormones in both pre-Ob and post-Ob primary human cell lines. This finding may have clinical relevance for patients at high risk of osteoporosis managed with rivaroxaban or other factor Xa inhibitors. PMID- 27661795 TI - Donald Ainslee Henderson, 1928-2016. PMID- 27661798 TI - The funny side. AB - The turn of the year kicked off with a new television series called Health anti Efficiency, billed as an NHS reform sitcom complete with Thatcherite trimmings. Some may find it difficult to raise a chuckle at the lighthearted banter with predictable one-liners and canned laughter. The ratings will give their own verdict on its popularity - would that calling a halt to the NHS changes were such a simple matter. PMID- 27661797 TI - The Department of Defense at the Forefront of a Global Health Emergency Response: Lessons Learned from the Ebola Outbreak. AB - Tasked with analyzing the effectiveness of the Department of Defense's (DoD's) global health engagements, the Uniformed Services University of the Health Sciences (USU) used the Measures Of Effectiveness in Defense Engagement and Learning (MODEL) study to conduct a qualitative analysis of the DoD's response efforts to the Ebola pandemic in West Africa. The research aims to summarize the findings of studies that monitor and evaluate the DoD's response to the Ebola pandemic or compare the effectiveness of different DoD response activities; it further aims to identify common themes around positive and negative lessons learned and recommendations that can be applied to future DoD humanitarian assistance and disaster response efforts. The search included documents and observations from PubMed, Disaster Lit: Resource Guide for Disaster Medicine and Public Health, the Joint Lessons Learned Information System, the DoD and US Africa Command websites, and Google Scholar. The records selected from the search were analyzed to provide insights on the DoD's humanitarian assistance and disaster response engagements that could be employed to inform future operations and policy. Furthermore, the research identifies strengths and gaps in military capabilities to respond to disasters, which can be used to inform future training and education courses. Overall, the findings demonstrate the importance of monitoring, evaluating, and assessing disaster response activities and provide new evidence to support the implementation of activities, in accordance with the Global Health Security Agenda, to strengthen all-threat prevention, detection, and response capabilities worldwide. PMID- 27661800 TI - New year honours list. AB - Margaret Brain, until recently President of the Royal College of Midwives, was made a Dame in the New Year Honours List as nurses again featured prominently in the awards. PMID- 27661799 TI - Caring for people with learning disabilities. AB - Nurses are ideally placed to provide an individualised service to people with learning disabilities living at home or in residential accommodation. Acting as key change agents, nurses can encourage clients to live as independently as possible in their own communities and can improve the quality of life offered to individuals and their families. This unit is relevant to UKCC PREP categories of Care Enhancement, Reducing Risk and Practice Development. PMID- 27661796 TI - Comprehensive Laboratory Evaluation of a Highly Specific Lateral Flow Assay for the Presumptive Identification of Bacillus anthracis Spores in Suspicious White Powders and Environmental Samples. AB - We conducted a comprehensive, multiphase laboratory evaluation of the Anthrax BioThreat Alert((r)) test strip, a lateral flow immunoassay (LFA) for the rapid detection of Bacillus anthracis spores. The study, conducted at 2 sites, evaluated this assay for the detection of spores from the Ames and Sterne strains of B. anthracis, as well as those from an additional 22 strains. Phylogenetic near neighbors, environmental background organisms, white powders, and environmental samples were also tested. The Anthrax LFA demonstrated a limit of detection of about 10(6) spores/mL (ca. 1.5 * 10(5) spores/assay). In this study, overall sensitivity of the LFA was 99.3%, and the specificity was 98.6%. The results indicated that the specificity, sensitivity, limit of detection, dynamic range, and repeatability of the assay support its use in the field for the purpose of qualitatively evaluating suspicious white powders and environmental samples for the presumptive presence of B. anthracis spores. PMID- 27661801 TI - London fog begins to clear. AB - The future of London's hospitals is finally being decided after Health Secretary Virginia Bottomley made the first in a series of'Tomlinson' announcements. But Mrs Bottomley is facing a continuing battle with health authorities intent on ignoring the findings of both the Tomlinson Report and the specialist review. PMID- 27661802 TI - ? AB - Penultimate presentations: Post-registration students Kim Miller (left), Gavin O'Sullivan and Anita Savage were among the is finalist nurses to be honoured as the second last intake to graduate from the Bethlem Royal Hospital and Maudsley Hospital in London. The final group to have the Royal seal' on their certificates will graduate next year, after which education will be run by The Nightingale Institute at Guy's and St Thomas' Hospitals. PMID- 27661803 TI - Dangerous patient list long overdue'. AB - News that hospitals and health authorities will be forced to keep a register of potentially dangerous patients released from psychiatric hospitals has been hailed as long overdue. PMID- 27661804 TI - ? AB - A recipe for success: Meals from around the world were cooked up by staff at St Charles I lospital as part of a fund-raising open day. The team from Portobello ward prepared food from Nigeria, Malaysia, Mauritius, Ghana, Morocco. China and Britain. The money will be used to organise activities for the ward's elderly patients. PMID- 27661806 TI - NHS restructuring. AB - * Government plans for a radical shake-up of NHS management structures will fail without the backing of staff, the National Association of Health Authorities and Trusts hies warned. PMID- 27661808 TI - PFC will not make savings promised. AB - Patient-focused care will not make the savings it promises, a new NHS report says - but it could help to 'blur' nursing into a new generic health profession. PMID- 27661807 TI - Managers told: 'Use clinical guidelines'. AB - A new initiative to ensure nurses, doctors and managers make use of research into the most cost-effective, high quality patient care available has been announced by the NHS Management Executive. PMID- 27661809 TI - ? AB - Eastern promise: Thirty Japanese nurses on a recent visit to the RCN's Institute of Advanced Nursing Education. The group spent a week studying infection control nursing and have now returned to Japan where they aim to develop Infection Control Specialist posts. PMID- 27661810 TI - Guernsey vote branded obscene by RCN. AB - A decision by Guernsey's ruling council not to ratify a United Nations convention on the elimination of discrimination against women has been branded 'obscene' by the RCN. PMID- 27661812 TI - NHS part-timers 'suffering'. AB - Part-time workers in the NHS - most of whom are women - face career discrimination with reduced access to training and inadequate childcare provision, according to an Institute of Manpower Studies report. PMID- 27661814 TI - Agencies desperate for staff. AB - Nursing agencies in London are facing a critical shortage of available staff to meet the demands of hospital and community units in the capital, the RCN has claimed. PMID- 27661813 TI - Hancock calls for lobbying on education. AB - A 'massive lobbying job' needs to be undertaken to secure the future of nurse education and fill a 'gaping policy vacuum', RCN General Secretary Christine Hancock has said. PMID- 27661815 TI - ? AB - That's Life star Gavin Campbell helped launch a patient comment scheme at Guy's and St Thomas' Hospital Trust. The Let us Know' scheme is designed to encourage feedback from patients, visitors and staff. Comments will be passed to relevant departments for action. With Gavin are nurse Kay Iowther and new mum lisa Ward. PMID- 27661816 TI - ICU workers face more stress. AB - Intensive care unit nurses face far more stress than those working on general wards, psychologists have found. PMID- 27661817 TI - Nurse victims often blame themselves. AB - Nurses who are the victims of sexual harassment at work frequently blame themselves, the conference heard. PMID- 27661820 TI - Sands launches teardrop sticker campaign. AB - SANDS, the Stillbirth and Neonatal Death Society, has incorporated its teardrop logo in a sticker that is to be used on notes to warn health professionals that a mother has lost her baby. PMID- 27661818 TI - Norwegian unions fight for the right to full-time positions. AB - Norway Too many of the country's nurses work part-time, according to the Norwegian Nurses Association (NNA). PMID- 27661821 TI - New design scanner eases patients' fears. AB - The fears of an estimated five per cent of patients intimidated by the enclosed scanners used for magnetic resonance imaging will be eased by a new design to be launched in the spring. PMID- 27661822 TI - Blood transfusion first for Southend Hospital. AB - A hospital in Essex has become the first in the UK to offer patients a full range of autologous blood components. PMID- 27661823 TI - Extending viability in transplant organs. AB - A synthetic opiate might help to prolong the viability of organs for transplant, American researchers say. PMID- 27661824 TI - Children and primary antibody deficiencies. AB - Rapid subcutaneous immunoglobulin infusions might be useful in the treatment of children with primary antibody deficiences, according to researchers. PMID- 27661825 TI - Criteria for elective aneurysm repair. AB - Surgical repair of abdominal aortic aneurysms less than 6cm in diameter is unnecessary and possibly detrimental, new research suggests. PMID- 27661826 TI - Prescribed drugs and hospital admissions. AB - Of 705 admissions to one care of the elderly unit, more than 100 were precipitated by drug therapy and could have been avoided, a pharmacist reports. PMID- 27661827 TI - Antenatal screening for trisomy 18 now feasible. AB - Screening for trisomy 18 in the second trimester could be a valuable addition to screening for trisomy 21, according to researchers. PMID- 27661828 TI - Children who care. AB - Care in the community is institutionalising a form of child abuse, says Dr Saul Becker, director of research for the Young Carers Project at Loughborough University. 'Community care relies heavily on I so-called informal carers, and we now know that many of them are children. PMID- 27661829 TI - It's not our job to cope with yobs. AB - I was pleased to read Christopher Goodall's call for a Nurse's Charter to protect staff against the unacceptable behaviour encouraged by the existence of the Patient's Charter (What about our rights? Viewpoint, December 8). PMID- 27661830 TI - Just shout back at bullying quacks. AB - I read RCN Scottish Secretary June Andrews' comments in your news story, Doctors 'are bullying junior nurses' (December 1), with surprise and disappointment. PMID- 27661831 TI - Get on platforms against Cuban heels. AB - As members of a group of health workers from UNISON who recently visited Cuba, we would like to inform readers of the suffering inflicted on the Cuban people by the lack of medical supplies as a result of the imposition of an economic blockade by the US. PMID- 27661832 TI - Teacher raises Montessori point. AB - Thank you for a well-written and well-presented research article, A computer assisted learning package (Clinical, December 8). PMID- 27661833 TI - Paed off for the children's sake. AB - I write to ask children's nurses how soon it will be before they are able to separate the words 'paediatric' and 'nursing' when the former is used to describe children's nursing? PMID- 27661834 TI - Wrongly furnished Chair confusion. AB - At the end of my letter in the December 8 issue (A woman's place is via the Home Office), I should have been described as former Chair of RCN Congress, not Council. PMID- 27661836 TI - Correction. AB - A news item in the December 1 issue incorrectly stated the telephone number of the National Schizophrenia Fellowship. It can be contacted on 081-547 3937. PMID- 27661835 TI - I can't even take money for granted. AB - I would like to say to all the students who have written in during the past few weeks complaining about the amount of rent they have to pay: think yourselves lucky. PMID- 27661837 TI - Information exchange. PMID- 27661839 TI - Confronting the Pain of Child Sexual Abuse Confronting the Pain of Child Sexual Abuse FSU London 86pp L5.00 0-905-17534-4. AB - Confronting the Pain of Child Sexual Abuse is a compact book full of information and ideas for working in the area of child sexual abuse (CSA). PMID- 27661838 TI - Nutrition Handbook for Nursing Practice, 2nd edition S Dudek Nutrition Handbook for Nursing Practice, 2nd edition 2nd edition J B Lippincott 736pp L27.95 0-397 54928-8. AB - The Nutrition Handbook for Nursing Practice is a uniquely and clearly presented reference book from the United States. PMID- 27661840 TI - Cancer Answers E Friedberg W H Freeman 186pp L10.95 0-7167-7024-5. AB - Cancer Answers: Encouraging Answers to 25 Questions You Were Always Afraid To Answer is an American book edited for the British market. PMID- 27661842 TI - ANS action plan to probe hardship cases. AB - A major RCN survey into student hardship is being launched as part of the Association of Nursing Students' new drive to win proper government funding for members on all courses. PMID- 27661841 TI - Student numbers plummet. AB - Nursing student numbers have fallen by a massive 35 per cent since 1983 and the figure could fall by a further 20 per cent this year if regions act on the latest government guidelines, the RCN has warned. PMID- 27661843 TI - National Student News. PMID- 27661844 TI - Talked up-beaten down. AB - It's right there in the philosophy of Project 2000 - 'students are agents for change'. Whoever thought that up should become a road sweeper and try to change this country's monetary policy. The level of impact would be about the same. PMID- 27661845 TI - Advice from the Royal College of Nursing. AB - Q What is RCN Congress, and how can I get involved? The Royal College of Nursing's annual Congress debates recommendations, resolutions and matters for discussion, which are submitted by RCN branches, national membership groups (which include the ANS), the RCN's governing Council, and other constituent parts of the College. PMID- 27661846 TI - Letters. AB - I read Daniel Law's article, Large Scale Discrimination, in No Limits issue One, with horror and sorrow. PMID- 27661848 TI - Career listings. AB - May 30-June 3 How to read and use results of nursing research' is the title of a course to be held by the European Oncology Nursing Society. The venue is Eerbeek, The Netherlands. The fee is Df1750. Grants are available. Details from Robbert van Bokhoven, Educational Department IK A, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands, tel 31 20 6172903, fax 31 20 6155904, or Brian Lake, Honorary Secretary, RCN Cancer Nursing Society, Royal Marsden Hospital, London SW3 6JJ. PMID- 27661850 TI - Effect of Hand Antisepsis Agent Selection and Population Characteristics on Surgical Site Infection Pathogens. AB - BACKGROUND: Selection of a pre-operative hand antisepsis agent has not been studied in relation to surgical site infection (SSI) culture data. In our hospital, we introduced an alcohol-based hand rub (ABR) in 2012 as an alternative to traditional aqueous surgical scrubs (TSS). It was the goal of this study to review any effect of this implementation on SSI pathogen characteristics. In addition, we sought to compare our SSI culture data with available National Healthcare Safety Network (NHSN) data. We hypothesized that SSI pathogens and resistant isolates are affected by surgical hand antisepsis technique. METHODS: Data collected prospectively between 2007 and 2014 were retrospectively analyzed for two time periods at the Veterans Affairs Boston Healthcare System (VABHS): Before ABR implementation (TSS group) and after (ABR group). Pathogen distribution and pathogenic isolate resistance profiles were compared for TSS and ABR, and similar comparisons, along with procedure-associated SSI comparisons, were made between VABHS and NHSN. All VABHS data were interpreted and categorized according to NHSN definitions. RESULTS: Compared with TSS (n = 4,051), ABR (n = 2,293) had a greater rate of Staphylococcus aureus (42.6% vs. 38.0%), Escherichia coli (12.8% vs. 9.9%), Pseudomonas aeruginosa (8.5% vs. 2.8%), and Enterobacter spp. (10.6% vs. 2.8%), and a lower rate of Klebsiella pneumoniae/K. oxytoca (4.3% vs. 8.5%) cultured from superficial and deep SSIs (p < 0.05). Of the S. aureus isolates, 35.0% and 44.4% were resistant to oxacillin/methicillin (MRSA) in ABR and TSS, respectively (p = 0.06). Looking at all SSIs, coagulase-negative staphylococci and K. pneumoniae/K. oxytoca at VABHS (4.0% and 10.4%, respectively) accounted for the biggest difference from NHSN (11.7% and 4.0%, respectively). Aside from MRSA, where there was no difference between VABHS and NHSN (42.9% vs. 43.7%, respectively; p = 0.87), statistically significant (p < 0.05) differences were observed among multi-drug-resistant K. pneumoniae/K. oxytoca (0% vs. 6.8%, respectively) and Escherichia coli (10.0% vs. 1.6%, respectively), as well as among extended-spectrum cephalosporin-resistant K. pneumoniae/K. oxytoca (4.8% vs. 13.2%, respectively) and Enterobacter (58.3% vs. 27.7%, respectively). VABHS had a greater proportion of SSIs in abdominal and vascular cases than did NHSN (48.6% vs. 22.5% and 13.2% vs. 1.5%, respectively). Overall, these differences were significant (p < 0.05). CONCLUSIONS: The TSS and ABR groups differed in the distribution of pathogens recovered. Those differences, along with SSI pathogen distribution, pathogenic isolate resistance profiles, and procedure-associated SSIs between VABHS and NHSN, warrant further investigation. PMID- 27661851 TI - Gaze Evoked Deformations of the Peripapillary Retina in Papilledema and Ischemic Optic Neuropathy. AB - Purpose: To examine the effects of horizontal eye movements on the shape of the peripapillary basement membrane layer (ppBM layer) in patients with papilledema, anterior ischemic optic neuropathy (AION) and normal eyes. Methods: Spectral domain optical coherence tomography (SD-OCT) axial rasters of the optic nerve were used to analyze the shape of the ppBM layer. We compared registered images in two eye positions: 10 degrees to 15 degrees of adduction and 30 degrees to 40 degrees of abduction from 80 patients (45 with papilledema, 15 with AION, and 20 normal eyes). Results: Horizontal eye movements induce a relative "seesaw like" shape deformation of the ppBM layer in patients with papilledema. On adduction, there is a relative posterior displacement temporal to the basement membrane opening (BMO) and an anterior displacement nasally (P = 0.001). The pattern reverses in abduction. Normal eyes and AION display similar but smaller changes in shape predominantly affecting the temporal side on adduction. The shape difference was significantly different for normal eyes (P = 0.03) and for AION (P = 0.01). Conclusions: Horizontal eye movements affect the shape of the ppBM layer. The deformation in normals and AION, in adduction, causes posterior displacement temporal to the BMO. In contrast, the deformations in papilledema are larger, involving temporal and nasal sides, presumably because of shifts in cerebrospinal fluid pressure against the scleral flange and hydraulic stiffening of the optic nerve sheath. The clinical importance of gaze-induced deformations is unknown but repetitive motion may be a factor in the genesis or progression of a variety of optic neuropathies. PMID- 27661849 TI - Variability in measures of health and health behavior among emerging adults 1 year after high school according to college status. AB - OBJECTIVE: To examine changes in health behaviors among US emerging adults 1 year after high school. PARTICIPANTS: The national sample of participants (N = 1,927), including those attending 4-year college/university (n = 884), 2-year colleges/technical schools (n = 588), and no college (n = 455), participated in annual spring surveys 2013-2014. METHODS: Health behaviors were assessed the last year of high school and first year of college; differences by college status controlling for previous-year values were estimated using regression analyses. RESULTS: Relative to 4-year college attendees, those attending technical school/community college were less likely to binge drink (odds ratio [OR] = 0.57, confidence interval [CI] = 0.38-0.86) but more likely to speed (OR = 1.26, CI = 1.0-2.84), consume sodas (OR = 1.57, CI = 1.0-2.47), and report lower family satisfaction (p < .01), with marginally more physical and depressive symptoms. College nonattendees reported more DWI (driving while intoxicated; OR = 1.60, CI = 1.05-2.47), soda drinking (OR = 2.51, CI = 1.76-3.59), oversleeping (OR = 4.78, CI = 3.65-8.63), and less family satisfaction (p < .04). CONCLUSIONS: Health risk behaviors among emerging adults varied by college status. PMID- 27661852 TI - The Optic Nerve in Moving Pictures. PMID- 27661853 TI - Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy. AB - Purpose: The purpose of this study was to investigate whether fibrocytes participate in formation of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous fluid and FVM samples were obtained during vitrectomy in patients with PDR. Samples from patients with macular hole or epiretinal membrane were used as controls. Vitreous fluid and FVM samples were subjected to immunohistochemical analysis. In addition, cells isolated from the vitreous fluid of PDR and control patients were cultured in serum-free medium. Fibrocytes were identified among these cells by morphological and immunohistochemical analyses. We examined the number of fibrocytes in PDR patients and control patients. Also, the concentrations of monocyte chemoattractant protein-1 (MCP-1), pentraxin3, and serum amyloid P (SAP) in vitreous fluid samples from PDR patients and control patients were determined by enzyme-linked immunosorbent assay. Results: Fibrocytes were observed in the vitreous and FVM samples from PDR patients. Cells cultured from the vitreous samples of PDR patients were spindle shaped and expressed fibrocyte markers. TGF beta1 induced differentiation of these cells into myofibroblasts. The number of fibrocytes was higher in samples from PDR patients than in samples from control patient. The vitreous fluid concentration of MCP-1 was significantly higher in PDR patients than in controls and showed a significant positive correlation with the number of fibrocytes from the vitreous fluid. Vitreous fluid concentrations of pentraxin3 and SAP were also higher in PDR patients than in control patients. Conclusions: These findings indicate that fibrocytes may be involved in development of the FVM in PDR. PMID- 27661854 TI - Evaluation of Nonperfused Retinal Vessels in Ischemic Retinopathy. AB - Purpose: Retinal ischemia has been traditionally assessed by fluorescein angiography, visualizing perfused vessels. However, this method does not provide any information about nonperfused vessels, and although it is often assumed that vessels in ischemic areas regress, we know little about how nonperfused retinal vessels change over time. Here, we aim to learn more about the long-term fate of nonperfused vessels in the retinal vasculature. Methods: Optical coherence tomography (OCT) was used to visualize perfusion as well as structural properties of the retinal vasculature in patients suffering from retinal vascular occlusions. In addition, postmortem tissue from a patient with long standing (6 years) central retinal vein occlusion (CRVO) was investigated, using immunohistochemistry on whole-mount retina and paraffin sections to visualize blood vessel components. Results: Comparing OCT angiography with enface OCT images revealed that in ischemic areas of the retina, nonperfused, larger vessels could be detected as hyperreflective structures in enface OCT images. Furthermore, analysis of a postmortem tissue sample from a CRVO patient with a large nonperfused region in the macula, revealed preservation of the basement membrane from all retinal vessels, including nonperfused, acellular vessels of all calibers. Conclusions: Our data suggests long-term preservation of vascular basement membrane in ischemic retina. This has implications for therapeutic approaches aiming to alleviate retinal ischemia via the regeneration of damaged vessels. PMID- 27661855 TI - The Immunoproteasome in Human Lens Epithelial Cells During Oxidative Stress. AB - Purpose: The immunoproteasome is known to generate peptides for antigen presentation. However, it has also been proposed to have additional functions such as stress response. The propensity of the immunoproteasome for degradation of oxidatively damaged proteins and peptides makes it interesting in the context of cataract formation and prevention. This study hypothesized that the immunoproteasome is present in human cataractous lenses and that oxidative stress will induce its expression, affect its proteolytic activity and its intracellular location in native cultured human lens epithelial cells (HLECs). Methods: The expression of the immunoproteasome and the constitutive proteasome subunits beta1i/beta1, beta2i/beta2, and beta5i/beta5 were studied by using Western blotting. The chymotrypsin-like activity was investigated for possible oxidative stress response. Inhibitors specific for the immuno- and constitutive proteasome, ONX-0914 and MG-132, respectively, were used to study their relative contributions to total proteasome activity. The intracellular location of the proteasomal subunits beta5i and beta5 was studied by immunocytochemistry. Results: Immunoproteasome subunits were detected both in the lens epithelium and in the lens fibers derived from cataract surgery. Oxidative stress to cultured HLECs upregulated the immunoproteasome but not the constitutive proteasome. The chymotrypsin-like activity decreased with increased oxidative stress and the two proteasome types contributed equally to total proteasome activity. Immunocytochemical labeling of subunit beta5i showed mainly cytosolic localization, whereas subunit beta5 was localized predominantly in the nucleus. H2O2-induced challenge increased the expression of the immunoproteasome. Conclusions: The present findings indicate a role for the immunoproteasome in oxidative stress management in the lens. PMID- 27661857 TI - Standing Balance Stability and the Effects of Light Touch in Adults With Profound Loss of Vision-An Exploratory Study. AB - Purpose: We evaluated the postural stability of adults with inherited profound vision loss and examined the effects of touch on their balance control. Methods: A total of 11 severely-sight impaired patients (mean [SD] age, 51.6 [5.3] years) and 11 control subjects (mean age, 49.7 [5.3] years) participated. Postural stability was measured using a force-balance platform eyes open/closed on a firm/foam surface under 3 test conditions: no touch, light touch, and unrestricted touch (UT), where "touch" involved placing their index finger on a rigid table. Average magnitude of center of foot pressure displacement was calculated. A somatosensory ratio (SR) was used to evaluate the somatosensory contribution to balance. A repeated measures ANOVA was used to investigate the effects of touch on standing balance. Results: Patients had a significantly increased SR compared to control subjects (mean [SD] SR controls = 1.2 [0.2], patients = 1.9 [0.5]; P < 0.01). There was a significant effect of touch, vision, and surface on balance control ("touch" F = 68.1, P < 0.01; "vision" F = 20.1, P < 0.01; "surface" F = 200.8, P < 0.01). Light touch attenuated sway in patients and controls. The effects were greater in controls when their vision was removed, and greater in patients when their somatosensory system was disrupted. Light touch was as effective as UT in attenuating sway. Conclusions: The results of this exploratory study suggest that patients with severe sight impairment show an increased somatosensory contribution to balance control compared to their normally sighted counterparts. Light touch significantly reduces sway amplitude in severely sight impaired adults when standing on the foam surface, that is, when the somatosensory system is perturbed. PMID- 27661856 TI - Assessing the Association of Mitochondrial Genetic Variation With Primary Open Angle Glaucoma Using Gene-Set Analyses. AB - Purpose: Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. Methods: We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. Results: We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). Conclusions: We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important. PMID- 27661858 TI - Corneal Hydration Control in Fuchs' Endothelial Corneal Dystrophy. AB - Purpose: To assess corneal hydration control across a range of severity of Fuchs' endothelial corneal dystrophy (FECD) by measuring the percent recovery per hour (PRPH) of central corneal thickness after swelling the cornea and to determine its association with corneal morphologic parameters. Methods: Twenty-three corneas of 23 phakic FECD patients and 8 corneas of 8 healthy control participants devoid of guttae were graded (modified Krachmer scale). Effective endothelial cell density (ECDe) was determined from the area of guttae and local cell density in confocal microscopy images. Steady-state corneal thickness (CTss) and standardized central corneal backscatter were derived from Scheimpflug images. Corneal swelling was induced by wearing a low-oxygen transmissible contact lens for 2 hours in the morning. De-swelling was measured over 5 hours after lens removal or until corneal thickness returned to CTss. Percent recovery per hour was 100 * (1 - e-k), where k was determined from CT(t) = (de-kt) + CTss, and where d was the initial change from CTss. Results: After contact lens wear, corneas swelled by 9% (95% CI 9-10). Percent recovery per hour was 49%/h (95% CI 41-57) in controls and 37%/h in advanced FECD (95% CI 29-43, P = 0.028). Low PRPH was associated with disease severity, low ECDe, and increased anterior and posterior corneal backscatter. Anterior backscatter was associated with PRPH in a multivariable model (R2 = 0.44). Conclusions: Corneal hydration control is impaired in advanced FECD and is inversely related to anterior corneal backscatter. Anterior corneal backscatter might serve as an indicator of impaired endothelium in FECD. PMID- 27661860 TI - Magnetism and multiferroicity of an isosceles triangular lattice antiferromagnet Sr3NiNb2O9. AB - Various experimental measurements were performed to complete the phase diagram of a weakly distorted triangular lattice system, Sr3NiNb2O9 with Ni(2+) , spin-1 magnetic ions. This compound possesses an isosceles triangular lattice with two shorter bonds and one longer bond. It shows a two-step magnetic phase transition at [Formula: see text] K and [Formula: see text] K at zero magnetic field, characteristic of an easy-axis anisotropy. In the magnetization curves, a series of magnetic phase transitions was observed such as an up-up-down phase at [Formula: see text] T with 1/3 of the saturation magnetization (M sat) and an oblique phase at [Formula: see text] T with [Formula: see text]/3 M sat. Intriguingly, the magnetic phase transition below T N2 is in tandem with the ferroelectricity, which demonstrates multiferroic behaviors. Moreover, the multiferroic phase persists in all magnetically ordered phases regardless of the spin structure. The comparison between the phase diagrams of Sr3NiNb2O9 and its sister compound with an equilateral triangular lattice antiferromagnet Ba3NiNb2O9 (Hwang et al 2012 Phys. Rev. Lett. 109 257205), illustrates how a small imbalance among exchange interactions change the magnetic ground states of the TLAFs. PMID- 27661859 TI - Polysialylated Neural Cell Adhesion Molecule Protects Against Light-Induced Retinal Degeneration. AB - Purpose: We previously demonstrated that neural cell adhesion molecule (NCAM) plays an important role in supporting the survival of injured retinal ganglion cells. In the current study, we used light-induced retinal degeneration (LIRD) as a model to investigate whether NCAM plays a functional role in neuroprotection and whether NCAM influences p75NTR signaling in modulating retinal cell survival. Methods: Retinas from wild-type (WT) and NCAM deficient (-/-) mice were tested by electroretinogram before and after LIRD, and changes in the protein expressions of NCAM, polysialic acid (PSA)-NCAM, p75NTR, and active caspase 3 were measured by immunoblot from 0 to 4 days after light induction. The effects of NCAM and PSA NCAM on p75NTR were examined by intraocular injections of the p75NTR function blocking antibody and/or the removal of PSA with endoneuraminidase-N prior to LIRD. Results: In WT mice, low levels of active caspase 3 activation were detected on the first day, followed by increases up to 4 days after LIRD. Conversely, in NCAM-/- mice, higher cleaved caspase 3 levels along with rapid reductions in electroretinogram amplitudes were found earlier at day 1, followed by reduced levels by day 4. The removal of PSA prior to LIRD induced earlier onset of retinal cell death, an effect delayed by the coadministration of endoneuraminidase-N and the p75NTR function-blocking antibody antiserum. Conclusions: These results indicate that NCAM protects WT retinas from LIRD; furthermore, the protective effect of NCAM is, at least in part, attributed to its effects on p75NTR. PMID- 27661862 TI - Ombitasvir-Paritaprevir-Ritonavir-Dasabuvir (Viekira Pak)-Induced Lactic Acidosis. AB - OBJECTIVE: To report a case series of three patients with hepatitis C virus infection who all presented with severe type B lactic acidosis shortly after starting treatment with ombitasvir-paritaprevir-ritonavir-dasabuvir. DESIGN: Case series. SETTING: ICU. PATIENTS: Three patients, all who had HCV cirrhosis with mild hepatic impairment (Child-Pugh A) and had started taking ombitasvir paritaprevir-ritonavir-dasabuvir within the preceding 2 weeks, presented with similar nonspecific symptoms of lethargy, fatigue, and nausea. All had elevated lactate levels at admission without evidence of hypovolemia, cardiogenic failure, or vasodilatory shock. INTERVENTIONS: All patients were given appropriate supportive intensive care for what was initially suspected to be sepsis, including a minimum of 30 mL/kg of IV fluids, infectious workup including blood cultures, broad-spectrum antibiotics, and mechanical ventilatory support. The first patient received continuous veno-venous hemofiltration. The second patient received hemodialysis. The third patient was initially started on hemodialysis despite high norepinephrine requirements and ultimately transitioned to continuous veno-venous hemofiltration. MEASUREMENTS AND MAIN RESULTS: The first patient died despite maximal intensive care. The second patient improved immediately upon starting hemodialysis and was extubated within 48 hours and discharged home. The third patient eventually became hypotensive and was treated with repeated sessions of renal replacement therapy. He ultimately was extubated and discharged home. The infectious workup was negative for all three patients, and antibiotics were discontinued after 2 days in the second and third patients. CONCLUSIONS: Ombitasvir-paritaprevir-ritonavir-dasabuvir may cause type B lactic acidosis. Further study is warranted to identify risk factors and elucidate the mechanisms of excessive lactate production. PMID- 27661861 TI - Hospital-Level Changes in Adult ICU Bed Supply in the United States. AB - OBJECTIVES: Although the number of intensive care beds in the United States is increasing, little is known about the hospitals responsible for this growth. We sought to better characterize national growth in intensive care beds by identifying hospital-level factors associated with increasing numbers of intensive care beds over time. DESIGN: We performed a repeated-measures time series analysis of hospital-level intensive care bed supply using data from Centers for Medicare and Medicaid Services. SETTING: All United States acute care hospitals with adult intensive care beds over the years 1996-2011. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We described the number of beds, teaching status, ownership, intensive care occupancy, and urbanicity for each hospital in each year of the study. We then examined the relationship between increasing intensive care beds and these characteristics, controlling for other factors. The study included 4,457 hospitals and 55,865 hospital-years. Overall, the majority of intensive care bed growth occurred in teaching hospitals (net, +13,471 beds; 72.1% of total growth), hospitals with 250 or more beds (net, +18,327 beds; 91.8% of total growth), and hospitals in the highest quartile of occupancy (net, +10,157 beds; 54.0% of total growth). In a longitudinal multivariable model, larger hospital size, teaching status, and high intensive care occupancy were associated with subsequent-year growth. Furthermore, the effects of hospital size and teaching status were modified by occupancy: the greatest odds of increasing ICU beds were in hospitals with 500 or more beds in the highest quartile of occupancy (adjusted odds ratio, 18.9; 95% CI, 14.0-25.5; p < 0.01) and large teaching hospitals in the highest quartile of occupancy (adjusted odds ratio, 7.3; 95% CI, 5.3-9.9; p < 0.01). CONCLUSIONS: Increasingly, intensive care bed expansion in the United States is occurring in larger hospitals and teaching centers, particularly following a year with high ICU occupancy. PMID- 27661863 TI - Quality Improvement Initiative for Severe Sepsis and Septic Shock Reduces 90-Day Mortality: A 7.5-Year Observational Study. AB - OBJECTIVE: To investigate the impact of a quality improvement initiative for severe sepsis and septic shock focused on the resuscitation bundle on 90-day mortality. Furthermore, effects on compliance rates for antiinfective therapy within the recommended 1-hour interval are evaluated. DESIGN: Prospective observational before-after cohort study. SETTING: Tertiary university hospital in Germany. PATIENTS: All adult medical and surgical ICU patients with severe sepsis and septic shock. INTERVENTION: Implementation of a quality improvement program over 7.5 years. MEASUREMENTS: The primary endpoint was 90-day mortality. Secondary endpoints included ICU and hospital mortality rates and length of stay, time to broad-spectrum antiinfective therapy, and compliance with resuscitation bundle elements. MAIN RESULTS: A total of 14,115 patients were screened. The incidence of severe sepsis and septic shock was 9.7%. Ninety-day mortality decreased from 64.2% to 45.0% (p < 0.001). Hospital length of stay decreased from 44 to 36 days (p < 0.05). Compliance with resuscitation bundle elements was significantly improved. Antibiotic therapy within the first hour after sepsis onset increased from 48.5% to 74.3% (p < 0.001). Multivariate analysis revealed blood cultures before antibiotic therapy (hazard ratio, 0.60-0.84; p < 0.001), adequate calculated antibiotic therapy (hazard ratio, 0.53-0.75; p < 0.001), 1-2 L crystalloids within the first 6 hours (hazard ratio 0.67-0.97; p = 0.025), and greater than or equal to 6 L during the first 24 hours (hazard ratio, 0.64-0.95; p = 0.012) as predictors for improved survival. CONCLUSIONS: The continuous quality improvement initiative focused on the resuscitation bundle was associated with increased compliance and a persistent reduction in 90-day mortality over a 7.5-year period. Based on the observational study design, a causal relationship cannot be proven, and respective limitations need to be considered. PMID- 27661865 TI - A Direct Observation Checklist to Measure Respect and Dignity in the ICU. AB - OBJECTIVE: Treating patients and family members with respect and dignity is a core objective of health care, yet it is unclear how best to measure this in the ICU setting. Accordingly, we sought to create a direct observation checklist to assess the "respect and dignity status" of an ICU. DESIGN: A draft checklist based on previous work was iteratively revised to enhance accuracy and feasibility. SETTING: Seven ICUs within the Johns Hopkins Health System. SUBJECTS: A total of 351 patient-clinician encounters with 184 different patients. INTERVENTIONS: Four study team members pilot tested the checklist between January and August 2015. MEASUREMENTS AND MAIN RESULTS: Standard psychometric analyses were performed. The direct observation checklist exhibits strong content and face validity as well as high reliability and internal consistency. All items load on one factor that supports the unidimensionality of the total index. Furthermore, concurrent validity of the direct observation checklist is demonstrated by statistically significant differences in mean scores between ICUs, between types of clinicians, and between patients' clinical status and mood. CONCLUSIONS: We rigorously developed, pilot tested, and analyzed a direct observation checklist designed to assess the extent to which patients and families in the ICU setting are treated with respect and dignity. Future research should validate this checklist in other settings and compare its results with other measures. Data gathered about individual items on the direct observation checklist could be used to target areas for training and education; doing so should help facilitate more respectful treatment of patients and their families. PMID- 27661866 TI - Agarose coated spherical micro resonator for humidity measurements. AB - A new type of fiber optic relative humidity (RH) sensor based on an agarose coated silica microsphere resonator is proposed and experimentally demonstrated. Whispering gallery modes (WGMs) in the micro resonator are excited by evanescent coupling using a tapered fiber with ~3.3 um waist diameter. A change in the relative humidity of the surrounding the resonator air induces changes in the refractive index (RI) and thickness of the Agarose coating layer. These changes in turn lead to a spectral shift of the WGM resonances, which can be related to the RH value after a suitable calibration. Studies of the repeatability, long term stability, measurement accuracy and temperature dependence of the proposed sensor are carried out. The RH sensitivity of the proposed sensor depends on the concentration of the agarose gel which determines the initial thickness of the deposited coating layer. Studies of the micro- resonators with coating layers fabricated from gels with three different Agarose concentrations of 0.5%, 1.125% and 2.25 wt./vol.% showed that an increase in the initial thickness of the coating material results in an increase in sensitivity but also leads to a decrease of quality factor (Q) of the micro resonator. The highest sensitivity achieved in our experiments was 518 pm/%RH in the RH range from 30% to 70%. The proposed sensor offers the advantages of a very compact form factor, low hysteresis, good repeatability, and low cross sensitivity to temperature. PMID- 27661867 TI - Innovative self-calibration method for accelerometer scale factor of the missile borne RINS with fiber optic gyro. AB - The calibration of an inertial measurement unit (IMU) is a key technique to improve the preciseness of the inertial navigation system (INS) for missile, especially for the calibration of accelerometer scale factor. Traditional calibration method is generally based on the high accuracy turntable, however, it leads to expensive costs and the calibration results are not suitable to the actual operating environment. In the wake of developments in multi-axis rotational INS (RINS) with optical inertial sensors, self-calibration is utilized as an effective way to calibrate IMU on missile and the calibration results are more accurate in practical application. However, the introduction of multi-axis RINS causes additional calibration errors, including non-orthogonality errors of mechanical processing and non-horizontal errors of operating environment, it means that the multi-axis gimbals could not be regarded as a high accuracy turntable. As for its application on missiles, in this paper, after analyzing the relationship between the calibration error of accelerometer scale factor and non orthogonality and non-horizontal angles, an innovative calibration procedure using the signals of fiber optic gyro and photoelectric encoder is proposed. The laboratory and vehicle experiment results validate the theory and prove that the proposed method relaxes the orthogonality requirement of rotation axes and eliminates the strict application condition of the system. PMID- 27661864 TI - Point Prevalence Study of Mobilization Practices for Acute Respiratory Failure Patients in the United States. AB - OBJECTIVE: Early mobility in mechanically ventilated patients is safe, feasible, and may improve functional outcomes. We sought to determine the prevalence and character of mobility for ICU patients with acute respiratory failure in U.S. ICUs. DESIGN: Two-day cross-sectional point prevalence study. SETTING: Forty-two ICUs across 17 Acute Respiratory Distress Syndrome Network hospitals. PATIENTS: Adult patients (>= 18 yr old) with acute respiratory failure requiring mechanical ventilation. INTERVENTIONS: We defined therapist-provided mobility as the proportion of patient-days with any physical or occupational therapy-provided mobility event. Hierarchical regression models were used to identify predictors of out-of-bed mobility. MEASUREMENTS AND MAIN RESULTS: Hospitals contributed 770 patient-days of data. Patients received mechanical ventilation on 73% of the patient-days mostly (n = 432; 56%) ventilated via an endotracheal tube. The prevalence of physical therapy/occupational therapy-provided mobility was 32% (247/770), with a significantly higher proportion of nonmechanically ventilated patients receiving physical therapy/occupational therapy (48% vs 26%; p <= 0.001). Patients on mechanical ventilation achieved out-of-bed mobility on 16% (n = 90) of the total patient-days. Physical therapy/occupational therapy involvement in mobility events was strongly associated with progression to out-of bed mobility (odds ratio, 29.1; CI, 15.1-56.3; p <= 0.001). Presence of an endotracheal tube and delirium were negatively associated with out-of-bed mobility. CONCLUSIONS: In a cohort of hospitals caring for acute respiratory failure patients, physical therapy/occupational therapy-provided mobility was infrequent. Physical therapy/occupational therapy involvement in mobility was strongly predictive of achieving greater mobility levels in patients with respiratory failure. Mechanical ventilation via an endotracheal tube and delirium are important predictors of mobility progression. PMID- 27661868 TI - Theoretical investigation of SERS nanosensors based on hybrid waveguides made of metallic slots and dielectric strips. AB - Surface-enhanced Raman spectroscopy (SERS) is widely used to sensitively detect molecules or markers in pharmacology, biology, etc. We study numerically the possibility to realize SERS detections directly on a photonic chip. It is presented that a SERS sensor created by combining a gold slot waveguide and a Si3N4 strip waveguide can be designed to excite enhanced Raman effects and extract their scattering signals on a chip. Using 3D finite difference time-domain simulations, the SERS processes, excitation of surface plasmon in slots and radiation of induced Raman dipoles, are analyzed to simulate SERS detections in reality. It demonstrates the influence of the geometrical parameters on the electromagnetic fields in slots and therefore the local enhancements, based on the |E|4-approximation. The results show that a SERS nanosensor can be achieved based on the hybrid waveguide. The integration of this sensor with a micro-laser and a micro-demultiplexer, could achieve an on-a chip and fully integrated system for portable and fast SERS detections. PMID- 27661869 TI - Rogue waves generation via nonlinear soliton collision in multiple-soliton state of a mode-locked fiber laser. AB - We report for the first time, rogue waves generation in a mode-locked fiber laser that worked in multiple-soliton state in which hundreds of solitons occupied the whole laser cavity. Using real-time spatio-temporal intensity dynamics measurements, it is unveiled that nonlinear soliton collision accounts for the formation of rogue waves in this laser state. The nature of interactions between solitons are also discussed. Our observation may suggest similar formation mechanisms of rogue waves in other systems. PMID- 27661870 TI - Broadband stimulated Raman scattering spectroscopy by a photonic time stretcher. AB - Stimulated Raman scattering spectroscopy is a powerful technique for label-free molecular identification, but its broadband implementation is technically challenging. We introduce and experimentally demonstrate a novel approach based on photonic time stretch. The broadband femtosecond Stokes pulse, after interacting with the sample, is stretched by a telecom fiber to ~15ns, mapping its spectrum in time. The signal is sampled through a fast analog-to-digital converter, providing single-shot spectra at 80-kHz rate. We demonstrate ~10 5 sensitivity over ~500cm-1 in the C-H region. Our results pave the way to high-speed broadband vibrational imaging for materials science and biophotonics. PMID- 27661872 TI - Actively stabilized silicon microrings with integrated surface-state-absorption photodetectors using a slope-detection method. AB - We propose and experimentally demonstrate actively stabilized silicon microrings with integrated surface-state-absorption (SSA) photodetectors using a slope detection method. Our proof-of-concept experiments reveal that the active stabilization using multiple discrete-step slope thresholds can effectively reduce the microring transmitted intensity variations upon various temperature modulation conditions. We demonstrate an actively stabilized microring transmission with intensity modulations within ~2.5 dB upon a 5mHz temperature modulation between 17 degrees C and 31 degrees C, which is ~7.5dB improved from without stabilization. The active alignment tolerance between the stabilized microring resonance wavelength and a carrier wavelength is ~0.16 nm over a 14 degrees C temperature modulation. We observe open eye-diagrams at a data transmission rate of up to 30 Gb/s under temperature modulations with actively stabilized silicon microrings. PMID- 27661871 TI - Terahertz polarization spectroscopy in the near-field zone of a sub-wavelength scale metal slit. AB - Time-domain spectroscopy is used to probe the polarization dependence of the terahertz-frequency absorption of alpha-lactose molecules in the near-field vicinity of a sub-wavelength-scale metal slit. The experimental result finds that the 0.53-THz absorption of this material has an unexpected polarization dependence, strongly coupled to the slit orientation; in particular, the electric wave in parallel polarization exhibits even complete vanishing of the otherwise resonant strong absorption. The physics behind this phenomena may be explained based on the Bethe's sub-wavelength diffraction: the electric field that is measured in the far field, but diffracted from a sub-wavelength-scale metal aperture, originates from solely magnetic dipole radiation and not from the electric dipole radiation, thus showing no electrically-coupled material response. PMID- 27661873 TI - Optically controlled in-line graphene saturable absorber for the manipulation of pulsed fiber laser operation. AB - We demonstrate an optically tunable graphene saturable absorber to manipulate the laser operation in pulsed fiber laser system. Owing to the strongly enhanced evanescent field interaction with monolayer graphene, we could realize an efficient control of modulation depth in the graphene saturable absorber by optical means through cross absorption modulation method. By integrating the tunable graphene saturable absorber into the fiber laser system, we could switch the laser operation from Q-switching through Q-switched mode-locking to continuous wave mode-locking by adjusting only the optical power of the control beam. In addition, we realized a hybrid Q-switching of fiber laser by periodical modulation of the absorption of the graphene saturable absorber, where we observed that the repetition rate of the Q-switched laser could be continuously tuned according to the modulation frequency of the applied external signal. PMID- 27661874 TI - Design of a quasi-2D photonic crystal optomechanical cavity with tunable, large x2-coupling. AB - We present the optical and mechanical design of a mechanically compliant quasi two-dimensional photonic crystal cavity formed from thin-film silicon in which a pair of linear nanoscale slots are used to create two coupled high-Q optical resonances. The optical cavity supermodes, whose frequencies are designed to lie in the 1500 nm wavelength band, are shown to interact strongly with mechanical resonances of the structure whose frequencies range from a few MHz to a few GHz. Depending upon the symmetry of the mechanical modes and the symmetry of the slot sizes, we show that the optomechanical coupling between the optical supermodes can be either linear or quadratic in the mechanical displacement amplitude. Tuning of the nanoscale slot size is also shown to adjust the magnitude and sign of the cavity supermode splitting 2J, enabling near-resonant motional scattering between the two optical supermodes and greatly enhancing the x2 coupling strength. Specifically, for the fundamental flexural mode of the central nanobeam of the structure at 10 MHz the per-phonon linear cross-mode coupling rate is calculated to be g~+-/2pi=1MHz, corresponding to a per-phonon x2-coupling rate of g~'/2pi=1kHz for a mode splitting 2J/2pi = 1 GHz which is greater than the radiation-limited supermode linewidths. PMID- 27661875 TI - All-optical depth coloring based on directional gating. AB - In non-contacting depth extraction there are several issues, such as the accuracy and the measurement speed. In the issue of the measurement speed, the computation cost for image processing is significant. We present an all-optical depth extraction method by coloring objects according to their depth. Our system is operated fully optically and both encoding and decoding processes are optically performed. Therefore, all-optical depth coloring has a distinct advantage to extract the depth information in real time without any computation cost. We invent a directional gating method to extract the points from the object which are positioned at the same distance. Based on this method, the objects look painted by different colors according to the distance when the objects are observed through our system. In this paper, we demonstrate the all-optical depth coloring system and verify the feasibility of our method. PMID- 27661876 TI - Characteristic matrix operation for finding global solution of one-time ray tracing optimization method. AB - The one-time ray-tracing optimization method is a fast way to design LED illumination systems [Opt. Express22, 5357 (2014)10.1364/OE.22.005357]. The method optimizes the performance of LED illumination systems by modifying the LEDs' luminous intensity distribution curve (LIDC) with a freeform lens, instead of modifying the illumination system structure. In finding the LEDs' LIDC for optimizing the illumination system's performance, the LEDs' LIDC found by means of a general gradient descent method can be trapped in a local solution. This study develops a matrix operation method to directly find the global solution of the LEDs' LIDC for the optimization of the illumination system's performance for any initial design of an illumination system structure. As compared with the gradient descent method, using the proposed characteristic matrix operation method to find the best LEDs' LIDC reduces the cost in time by several orders of magnitude. The proposed characteristic matrix operation method ensures that the one-time ray-tracing optimization method is an efficient and reliable method for designing LED illumination systems. PMID- 27661877 TI - Evolution of polarization dependent microstructures induced by high repetition rate femtosecond laser irradiation in glass. AB - We report the observation of an anomalous polarization dependent process in an isotropic glass induced by long time stationary irradiation of a high repetition rate near-infrared femtosecond laser. Two distinctive types of polarization dependent microstructures were induced at different irradiation stages. At early stage (a few seconds), a dumbbell-shaped structure elongated perpendicularly to the laser polarization formed at the top of the modified region, which was later erased by further irradiation. At later stage (above 30 s), bubbles filled with O2 formed by the irradiation, which were distributed along the laser polarization at a distance far beyond the radius of the laser beam. Based on a simple modeling of light reflection on boundaries, a thermal accumulation process was proposed to explain the formation and evolution of the dumbbell-shaped microstructure. The possible factors responsible for polarization dependent distribution of bubbles are discussed, which needs further systematic investigations. The results may be helpful in the development of femtosecond laser microprocessing for various applications. PMID- 27661878 TI - Mueller imaging polarimetry of holographic polarization gratings inscribed in azopolymer films. AB - Three types of polarization gratings have been recorded in azopolymer films by the symmetrical superposition of different orthogonal pairs of polarized beams. The inscribed holographic elements have been analyzed microscopically in a Mueller polarimeter in order to image the optical anisotropies photoinduced in the film. In the most of cases, the spatial modulation of diattenuation, birefringence, and optical rotation reproduced quite well previous results reported in the literature. Nevertheless, in the particular case of coherent superposition of p- and s-polarized beams, the spatial frequency for optical rotation (related to the Stokes parameter V) was different from the one observed in linear anisotropy (related to the Stokes parameter U). It is shown by theory and experiment that, in the polarized field used to record this polarization grating, the fourth-Stokes parameter changes sign, which implies a change in circular polarization handedness, practically once between two adjacent maxima. PMID- 27661879 TI - Two-probe optical encoder for absolute positioning of precision stages by using an improved scale grating. AB - In this paper, a novel optical encoder enabling the simultaneous measurement of displacement and the position of precision stages is presented. The encoder is composed of an improved single-track scale grating and a compact two-probe reading head. In the scale grating, multiple reference codes are physically superimposed onto the incremental grooves, in contrast to conventional designs, where an additional track is necessary. The distribution of the reference codes follows a specific mathematical algorithm. For the reading head, a two-probe structure is designed to identify the discrete reference codes by means of the superimposition of the codes with a stationary mask and to read the continuous incremental grooves by means of a grating interferometry, respectively. A prototype encoder was designed, constructed and evaluated, and experimental results show that the distance code precision achieved is 0.5 MUm, while the linearity error of the linear displacement measurement is less than 0.06%. PMID- 27661880 TI - Unidirectional, dual-comb lasing under multiple pulse formation mechanisms in a passively mode-locked fiber ring laser. AB - Dual-comb lasers simultaneously generating asynchronous ultrashort pulses could be an intriguing alternative to the current dual-laser comb source. When generated through a common light path, the low common-mode noises and good coherence between the pulse trains could be realized. Here we demonstrate the completely common-path, unidirectional dual-comb lasing using a carbon nanotube saturable absorber with additional pulse narrowing and broadening mechanisms. The interactions between multiple soliton formation mechanisms result in bifurcation into unusual two-pulse states with pulses of four-fold bandwidth difference and tens-of-Hz repetition rate difference. Coherence between the pulses is verified by the asynchronous cross-sampling and dual-comb spectroscopy measurements. PMID- 27661881 TI - Distributed measurement of hydrostatic pressure based on Brillouin dynamic grating in polarization maintaining fibers. AB - High-sensitivity distributed measurement of hydrostatic pressure is experimentally demonstrated by optical time-domain analysis of Brillouin dynamic grating (BDG) in polarization maintaining fibers (PMF's). The spectral shift of the BDG in four different types of PMF's are investigated under hydrostatic pressure variation from 14.5 psi (1 bar) to 884.7 psi (61 bar) with less than 2 m spatial resolution. The pressure sensitivity of BDG frequency is measured to be 1.69, + 0.65, + 0.78, and + 0.85 MHz/psi for a PM photonic crystal fiber (PM PCF), two Bow-tie fibers, and a PANDA fiber, respectively, which is about 65 to 169 times larger than that of Brillouin frequency-based pressure sensing. PMID- 27661882 TI - Measurement of near-wall 3D flow velocity from wave-guiding micro-pillars. AB - The measurement of near-wall flow in a plane close to the wall is achieved using the wave-guiding feature of transparent flexible micro-pillars which are attached in a 2D array to a surface and bend with the flow. Optical detection of bending from below the surface and application of auto-correlation methods provide mean and fluctuating part of the components of the wall-parallel velocity components. In addition, the wall-normal fluid motion is determined from spatial gradients in the array. The data provide the three-component velocity vector field in a plane close to the wall as well as their statistics. PMID- 27661883 TI - Birefringence effects in multi-core fiber: coupled local-mode theory. AB - In this paper, we evaluate experimentally and model theoretically the intra- and inter-core crosstalk between the polarized core modes in single-mode multi-core fiber media including temporal and longitudinal birefringent effects. Specifically, extensive experimental results on a four-core fiber indicate that the temporal fluctuation of fiber birefringence modifies the intra- and inter core crosstalk behavior in both linear and nonlinear optical power regimes. To gain theoretical insight into the experimental results, we introduce an accurate multi-core fiber model based on local modes and perturbation theory, which is derived from the Maxwell equations including both longitudinal and temporal birefringent effects. Numerical calculations based on the developed theory are found to be in good agreement with the experimental data. PMID- 27661884 TI - Design trade-off and proof of concept for LOUPE, the Lunar Observatory for Unresolved Polarimetry of Earth. AB - We provide a proof of the technical feasibility of LOUPE, the first integral field snapshot spectropolarimeter, designed to monitor the reflected flux and polarization spectrum of Earth. These are to be used as benchmark data for the retrieval of biomarkers and atmospheric and surface characteristics from future direct observations of exoplanets. We perform a design trade-off for an implementation in which LOUPE performs snapshot integral-field spectropolarimetry at visible wavelengths. We used off-the-shelf optics to construct a polarization modulator, in which polarization information is encoded into the spectrum as a wavelength-dependent modulation, while spatial resolution is maintained using a micro-lens array. The performance of this design concept is validated in a laboratory setup. Our proof-of-concept is capable of measuring a grid of 50 * 50 polarization spectra between 610 and 780 nm of a mock target planet - proving the merit of this design. The measurements are affected by systematic noise on the percent level, and we discuss how to mitigate this in future iterations. We conclude that LOUPE can be small and robust while meeting the science goals of this particular space application, and note the many potential applications that may benefit from our concept for doing snapshot integral-field spectropolarimetry. PMID- 27661885 TI - Efficient, tunable flip-chip-integrated III-V/Si hybrid external-cavity laser array. AB - We demonstrate a surface-normal coupled tunable hybrid silicon laser array for the first time using passively-aligned, high-accuracy flip chip bonding. A 2x6 III-V reflective semiconductor optical amplifier (RSOA) array with integrated total internal reflection mirrors is bonded to a CMOS SOI chip with grating couplers and silicon ring reflectors to form a tunable hybrid external-cavity laser array. Waveguide-coupled wall plug efficiency (wcWPE) of 2% and output power of 3 mW has been achieved for all 12 lasers. We further improved the performance by reducing the thickness of metal/dielectric stacks and achieved 10mW output power and 5% wcWPE with the same integration techniques. This non invasive, one-step back end of the line (BEOL) integration approach provides a promising solution to high density laser sources for future large-scale photonic integrated circuits. PMID- 27661886 TI - High-gain 87 cm-1 Raman line of KYW and its impact on continuous-wave Raman laser operation. AB - We report a quasi-continuous-wave external cavity Raman laser based on potassium yttrium tungstate (KYW). Laser output efficiency and spectrum are severely affected by the presence of high gain Raman modes of low frequency (< 250 cm 1) that are characteristic of this crystal class. Output spectra contained frequency combs spaced by the low frequency modes but with the overall pump-to Stokes conversion efficiency at least an order of magnitude lower than that typically obtained in other crystal Raman lasers. We elucidate the primary factors affecting laser performance by measuring the Raman gain coefficients of the low energy modes and numerically modeling the cascading dynamics. For a pump polarization aligned to the Ng crystallo-optic axis, the 87 cm 1 Raman mode has a gain coefficient of 9.2 cm/GW at 1064 nm and a dephasing time T2 = 9.6 ps, which are both notably higher than for the 765 cm-1 mode usually considered to be the prominent Raman mode of KYW. The implications for continuous-wave Raman laser design and the possible advantages for applications are discussed. PMID- 27661887 TI - Adaptive multiphoton endomicroscopy through a dynamically deformed multicore optical fiber using proximal detection. AB - This paper demonstrates multiphoton excited fluorescence imaging through a polarisation maintaining multicore fiber (PM-MCF) while the fiber is dynamically deformed using all-proximal detection. Single-shot proximal measurement of the relative optical path lengths of all the cores of the PM-MCF in double pass is achieved using a Mach-Zehnder interferometer read out by a scientific CMOS camera operating at 416 Hz. A non-linear least squares fitting procedure is then employed to determine the deformation-induced lateral shift of the excitation spot at the distal tip of the PM-MCF. An experimental validation of this approach is presented that compares the proximally measured deformation-induced lateral shift in focal spot position to an independent distally measured ground truth. The proximal measurement of deformation-induced shift in focal spot position is applied to correct for deformation-induced shifts in focal spot position during raster-scanning multiphoton excited fluorescence imaging. PMID- 27661888 TI - Theoretical investigation on nonlinear optical effects in laser trapping of dielectric nanoparticles with ultrafast pulsed excitation. AB - The use of low-power high-repetition-rate ultrafast pulsed excitation in stable optical trapping of dielectric nanoparticles has been demonstrated in the recent past; the high peak power of each pulse leads to instantaneous trapping of a nanoparticle with fast inertial response and the high repetition-rate ensures repetitive trapping by successive pulses However, with such high peak power pulsed excitation under a tight focusing condition, nonlinear optical effects on trapping efficiency also become significant and cannot be ignored. Thus, in addition to the above mentioned repetitive instantaneous trapping, trapping efficiency under pulsed excitation is also influenced by the optical Kerr effect, which we theoretically investigate here. Using dipole approximation we show that with an increase in laser power the radial component of the trapping potential becomes progressively more stable but the axial component is dramatically modulated due to increased Kerr nonlinearity. We justify that the relevant parameter to quantify the trapping efficiency is not the absolute depth of the highly asymmetric axial trapping potential but the height of the potential barrier along the beam propagation direction. We also discuss the optimal excitation parameters leading to the most stable dipole trap. Our results show excellent agreement with previous experiments. PMID- 27661889 TI - Expectation maximization and the retrieval of the atmospheric extinction coefficients by inversion of Raman lidar data. AB - We consider the problem of retrieving the aerosol extinction coefficient from Raman lidar measurements. This is an ill-posed inverse problem that needs regularization, and we propose to use the Expectation-Maximization (EM) algorithm to provide stable solutions. Indeed, EM is an iterative algorithm that imposes a positivity constraint on the solution, and provides regularization if iterations are stopped early enough. We describe the algorithm and propose a stopping criterion inspired by a statistical principle. We then discuss its properties concerning the spatial resolution. Finally, we validate the proposed approach by using both synthetic data and experimental measurements; we compare the reconstructions obtained by EM with those obtained by the Tikhonov method, by the Levenberg-Marquardt method, as well as those obtained by combining data smoothing and numerical derivation. PMID- 27661890 TI - Spectral filtering using active metasurfaces compatible with narrow bandgap III-V infrared detectors. AB - Narrow-bandgap semiconductors such as alloys of InAsAlSb and their heterostructures are considered promising candidates for next generation infrared photodetectors and devices. The prospect of actively tuning the spectral responsivity of these detectors at the pixel level is very appealing. In principle, this could be achieved with a tunable metasurface fabricated monolithically on the detector pixel. Here, we present first steps towards that goal using a complementary metasurface strongly coupled to an epsilon-near-zero (ENZ) mode operating in the long-wave region of the infrared spectrum. We fabricate such a coupled system using the same epitaxial layers used for infrared pixels in a focal plane array and demonstrate the existence of ENZ modes in high mobility layers of InAsSb. We confirm that the coupling strength between the ENZ mode and the metasurface depends on the ENZ layer thickness and demonstrate a transmission modulation on the order of 25%. We further show numerically the expected tunable spectral behavior of such coupled system under reverse and forward bias, which could be used in future electrically tunable detectors. PMID- 27661892 TI - Reflective liquid crystal hybrid beam-steerer. AB - We report on efficient optical beam-steering using a hot-embossed reflective blazed grating in combination with liquid crystal. A numerical simulation of the electrical switching characteristics of the liquid crystal is performed and the results are used in an FDTD optical simulator to analyze the beam deflection. The corresponding experiment on the realized device is performed and is found to be in good agreement. Beam deflection angles of 4.4 degrees upon perpendicular incidence are found with low applied voltages of 3.4 V. By tilting the device with respect to the incoming optical beam it can be electronically switched such that the beam undergoes either total internal reflection or reflection with a tunable angle. PMID- 27661891 TI - Refocusing distance of a standard plenoptic camera. AB - Recent developments in computational photography enabled variation of the optical focus of a plenoptic camera after image exposure, also known as refocusing. Existing ray models in the field simplify the camera's complexity for the purpose of image and depth map enhancement, but fail to satisfyingly predict the distance to which a photograph is refocused. By treating a pair of light rays as a system of linear functions, it will be shown in this paper that its solution yields an intersection indicating the distance to a refocused object plane. Experimental work is conducted with different lenses and focus settings while comparing distance estimates with a stack of refocused photographs for which a blur metric has been devised. Quantitative assessments over a 24 m distance range suggest that predictions deviate by less than 0.35 % in comparison to an optical design software. The proposed refocusing estimator assists in predicting object distances just as in the prototyping stage of plenoptic cameras and will be an essential feature in applications demanding high precision in synthetic focus or where depth map recovery is done by analyzing a stack of refocused photographs. PMID- 27661893 TI - Dependence of Raman and absorption spectra of stacked bilayer MoS2 on the stacking orientation. AB - Stacked bilayer molybdenum disulfide (MoS2) exhibits interesting physical properties depending on the stacking orientation and interlayer coupling strength. Although optical properties, such as photoluminescence, Raman, and absorption properties, are largely dependent on the interlayer coupling of stacked bilayer MoS2, the origin of variations in these properties is not clearly understood. We performed comprehensive confocal Raman and absorption mapping measurements to determine the dependence of these spectra on the stacking orientation of bilayer MoS2. The results indicated that with 532-nm laser excitation, the Raman scattering intensity gradually increased upon increasing the stacking angle from 0 degrees to 60 degrees , whereas 458-nm laser excitation resulted in the opposite trend of decreasing Raman intensity with increasing stacking angle. This opposite behavior of the Raman intensity dependence was explained by the varying resonance condition between the Raman excitation wavelength and C exciton absorption energy of bilayer MoS2. Our work sheds light on the intriguing effect of the subtle interlayer interaction in stacked MoS2 bilayers on the resulting optical properties. PMID- 27661894 TI - Ultracompact transverse magnetic mode-pass filter based on one-dimensional photonic crystals with subwavelength structures. AB - We propose and experimentally demonstrate an ultracompact transverse magnetic (TM) mode pass filter based on a rectangularly-shaped one-dimensional (1-D) photonic crystal silicon waveguide with an extremely high polarization extinction ratio (PER) of >30 dB and a low insertion loss (IL) of ~1 dB. The device structure of the TM mode-pass filter is numerically simulated using a three dimensional (3-D) finite difference time domain (FDTD) method. The proposed device supports its fundamental TM mode only, whereas the transverse electric (TE) mode is reflected by the 1-D photonic crystals (PhCs). The measured PER of the fabricated TM mode-pass filter is ~34 dB, and the IL is about 1 dB. The entire device length is about 4 MUm. Our simulation results predict that the device bandwidth of 30 dB PER is about 200 nm. PMID- 27661895 TI - Plasmonic quadrant lens for beam-position sensing. AB - We present the design of a plasmonic quadrant lens (QL) which is capable of coupling the light from free space into surface plasmon polaritons (SPPs) and focusing them into four directions, depending on the polarization content of the incident light. The lens is composed of a set of uniform nanogrooves etched on a gold film. Two types of QLs with four and eight foci are realized. We further propose QLs as a plasmonic version of well-known quadrant detectors for beam position sensing through a center location algorithm. The sensitivity of the device is also investigated for both linear and circular polarized incidences. Calculation results show that the four-focus QL offers a large effective detecting area and the eight-focus QL enables beam-position sensing to be operated with two different sensitivities simultaneously. PMID- 27661896 TI - Improving the modulation bandwidth of LED by CdSe/ZnS quantum dots for visible light communication. AB - Visible light communication (VLC) is an advanced and high-efficiency wireless communication technology. As one of the most important light sources in VLC, conventional white light emitting diode (WLED) based on Y3Al5O12:Ce3+ (YAG:Ce) phosphor limits the system transmitting rate severely due to its narrow modulation bandwidth. Considering the short fluorescent lifetime of quantum dots (QDs), QD LEDs with wide modulation bandwidths were designed here to improve the transmitting rate of VLC. CdSe/ZnS core/shell QDs and related luminescent microspheres (LMS) were implemented as light conversion materials for the QD LEDs. Compared with conventional phosphor WLED, the proposed QD-LED and QD-WLED reached maximum improvement on modulation bandwidth at 74.19% and 67.75% respectively. Furthermore, mathematical modeling of smearing was analyzed to establish the relationship between fluorescent lifetime and modulation bandwidth. Our findings will provide an effective solution of white LEDs for high speed VLC. PMID- 27661897 TI - Generation of stochastic electromagnetic beams with complete controllable coherence. AB - We generate a stochastic electromagnetic beam (SEB) with complete controllable coherence, that is, the coherence degree can be controlled independently along two mutually perpendicular directions. We control the coherence of the SEB by adjusting the phase modulation magnitude applied onto two crossed phase only spatial light modulators. We measure the beam's coherence properties using Young's interference experiment, as well as the beam propagation factor. It is shown that the experimental results are consistent with our theoretical predictions. PMID- 27661898 TI - On the analytical formulation of excess noise in avalanche photodiodes with dead space. AB - Simple, approximate formulas are developed to calculate the mean gain and excess noise factor for avalanche photodiodes using the dead-space multiplication theory in the regime of small multiplication width and high applied electric field. The accuracy of the approximation is investigated by comparing it to the exact numerical method using recursive coupled integral equations and it is found that it works for dead spaces up to 15% of the multiplication width, which is substantial. The approximation is also tested for real materials such as GaAs, InP and Si for various multiplication widths, and the results found are accurate within ~ 15% of the actual noise, which is a significant improvement over the local-theory noise formula. The results obtained for the mean gain also confirm the recently reported relationship between experimentally determined local ionization coefficients and the enabled non-local ionization coefficients. PMID- 27661899 TI - Demonstration of all-optical MDM/WDM switching for short-reach networks. AB - Mode division multiplexing (MDM) has been widely investigated in optical transmission systems and networks to improve network capacity. However, the MDM receiver is always expensive and complex because coherent detection and multiplex input-and-multiplex-output (MIMO) digital signal processing (DSP) are required to demultiplex each spatial mode. In this paper, we investigate the application of MDM in short-reach scenarios such as datacenter networking. Two-dimensional MDM and wavelength division multiplexing node structure based on low modal-crosstalk few-mode fiber (FMF) and components is proposed, in which signal in each mode or wavelength can be independently switched. We experimentally demonstrate independent adding, dropping and switching functionalities with two linearly polarized modes and four wavelength channels over a total 11.8-km 2-mode low modal-crosstalk FMFs. The structure is simple without coherent detection or MIMO DSP. Only slight penalties of receiver sensitivity are observed for all switching operations. The influence of modal-crosstalk accumulation for cascaded switching nodes is also investigated. PMID- 27661900 TI - Solid-state 3D imaging using a 1nJ/100ps laser diode transmitter and a single photon receiver matrix. AB - A 3D imaging concept based on pulsed time-of-flight focal plane imaging is presented which can be tailored flexibly in terms of performance parameters such as range, image update rate, field-of-view, 2D resolution, depth accuracy, etc. according to the needs of different applications. The transmitter is based on a laser diode operating in enhanced gain-switching mode with a simple MOS/CMOS switch current driver and capable of producing short (~100ps FWHM) high energy (up to nJ) pulses at a high pulsing rate. The receiver consists of 2D SPAD and TDC arrays placed on the same die, but in separate arrays. Paraxial optics can be used to illuminate the target field-of-view with the receiver placed at the focal plane of the receiver lens. To validate the concept, a prototype system is presented with a bulk laser diode/MOS driver operating at a wavelength of 870nm with a pulsing rate of 100kHz as the transmitter and a single-chip 9x9 SPAD array with 10-channel TDC as the receiver. The possibility of using this method as a solid-state solution to the task of 3D imaging is discussed in the light of the results derived from this prototype. PMID- 27661901 TI - Self-phase modulation in highly confined submicron Ta2O5 channel waveguides. AB - Optical spectra broadening as a result self-phase modulation in a channel waveguide fabricated on a high quality tantalum pentoxide (Ta2O5) film by using RF sputtering is measured. The full width at half maximum of the optical spectra for transverse electric (TE)/transverse magnetic (TM) polarizations of 42.5/31.7 nm is obtained using pulses of 10 nm at a wavelength of 800 nm with a peak-coupled power of 43.77 W. The nonlinear Kerr coefficients of 2.14 * 10-14 cm2/W and 1.92 * 10-14 cm2/W for TE and TM polarizations, respectively, are then extracted from the experiments using a theoretical model based on the method of moments. The obtained results on the nonlinearity further suggest that Ta2O5 is a promising material to develop nonlinear waveguide devices for integrated photonics. PMID- 27661902 TI - OAM-labeled free-space optical flow routing. AB - Space-division multiplexing allows unprecedented scaling of bandwidth density for optical communication. Routing spatial channels among transmission ports is critical for future scalable optical network, however, there is still no characteristic parameter to label the overlapped optical carriers. Here we propose a free-space optical flow routing (OFR) scheme by using optical orbital angular moment (OAM) states to label optical flows and simultaneously steer each flow according to their OAM states. With an OAM multiplexer and a reconfigurable OAM demultiplexer, massive individual optical flows can be routed to the demanded optical ports. In the routing process, the OAM beams act as data carriers at the same time their topological charges act as each carrier's labels. Using this scheme, we experimentally demonstrate switching, multicasting and filtering network functions by simultaneously steer 10 input optical flows on demand to 10 output ports. The demonstration of data-carrying OFR with nonreturn-to-zero signals shows that this process enables synchronous processing of massive spatial channels and flexible optical network. PMID- 27661903 TI - Single-beam heterodyne FAST CARS microscopy. AB - We demonstrate, for the first time, single-beam heterodyne FAST CARS imaging without data post-processing and with nonresonant background subtraction in a simple setup via the real-time piezo modulation of the probe delay. Our fast signal acquisition scheme does not require a spatial light modulator in the pulse shaper, and is suitable for high-resolution imaging and time-resolved dynamics. In addition, the spectral detection of the back-scattered FAST CARS signal is incorporated into the pulse shaper, allowing for a compact and more efficient design. Such epi-detection capability is demonstrated by imaging Si and MoS2 microstructures. PMID- 27661904 TI - 3.375-Gb/s RGB-LED based WDM visible light communication system employing PAM-8 modulation with phase shifted Manchester coding. AB - Optical background noise and second-order nonlinear distortions are two main challenges faced by indoor high-speed VLC system. In this paper, a novel phase shifted Manchester (PS-Manchester) coding based on PAM-8 is proposed and experimentally demonstrated to mitigate these noise and distortions. With the aid of PS-Manchester coding and WDM, a total data rate of 3.375-Gb/s can be successfully achieved in the RGB-LED based VLC system. The BER is under 7% HD-FEC limit of 3.8x10-3 after 1-m indoor free space transmission. To the best of our knowledge, this is the highest data rate ever achieved in PAM VLC systems. PMID- 27661905 TI - Fast coherent manipulation of quantum states in open systems. AB - We present a method to manipulate quantum states in open systems. It is shown that a high-fidelity quantum state may be generated by designing an additional Hamiltonian without rotating wave approximation. Moreover, we find that a coherent transfer is possible using quantum feedback control even when feedback parameters and noise strength can not be exactly controlled. Our results demonstrate the feasibility of constructing the shortcuts to adiabatic passage beyond rotating wave approximation in open systems. PMID- 27661906 TI - Ultra-stable high-power mid-infrared optical parametric oscillator pumped by a super-fluorescent fiber source. AB - The longterm stability of the laser system is very important in many applications. In this letter, an ultra-stable, broadband, mid-infrared (MIR) optical parametric oscillator (OPO) pumped by a super-fluorescent fiber source is demonstrated. An idler MIR output power of 11.3 W with excellent beam quality was obtained and the corresponding pump-to-idler conversion slope efficiency was 15.9%. Furthermore, during 1h measurement at full power operation, the peak-to peak fluctuation of idler output power was less than 1.9% and the corresponding standard deviation was less than 0.4% RMS, which was much better than that of a traditional single mode fiber laser pumped OPO system (10.9% for peak-to-peak fluctuation and 1.8% RMS for the standard deviation) in another experiment for comparison. To our knowledge, this is the first demonstration on a high-power, ultra-stable OPO system by using the modefree pump source, which offered an effective approach to achieve an ultra-stable MIR source and broadened the range of the super-fluorescent fiber source applications. PMID- 27661907 TI - All fiber M-Z interferometer for high temperature sensing based on a hetero structured cladding solid-core photonic bandgap fiber. AB - We proposed and experimentally demonstrated a high temperature fiber sensor using a hetero-structured cladding solid-core photonic bandgap fiber (HCSC-PBGF) for the first time to our knowledge. A hetero-structured cladding solid-core photonic bandgap fiber is designed and fabricated that supports vibrant core mode and cladding mode transmission. Then, an all fiber M-Z interference sensor is constructed by splicing single mode fiber at both ends of HCSC-PBGF without any other micromachining. The transmission characteristics of HCSC-PBGF are analyzed with a full-vector beam propagation method and a full-vector finite element method, and the simulation results are consistent with experiment results. The sensitivity of this fiber sensor is as high as 0.09 nm/ degrees C when operating from room temperature to 1000 degrees C, and the fringe contrast keeps stable and clear. It is obvious that this all fiber sensor will have great application prospects in fiber sensing with the advantages of a compact structure, high sensitivity, and cost-effectiveness. PMID- 27661908 TI - Differentiation of normal and leukemic cells by 2D light scattering label-free static cytometry. AB - Two-dimensional (2D) light scattering patterns of single microspheres, normal granulocytes and leukemic cells are obtained by label-free static cytometry. Statistical results of experimental 2D light scattering patterns obtained from standard microspheres with a mean diameter of 4.19 MUm agree well with theoretical simulations. High accuracy rates (greater than 92%) for label-free differentiation of normal granulocytes and leukemic cells, both the acute and chronic leukemic cells, are achieved by analyzing the 2D light scattering patterns. Our label-free static cytometry is promising for leukemia screening in clinics. PMID- 27661909 TI - Constellation recovery and impairment evaluation through minimization of the blind EVM. AB - We present a new method, blind EVM minimization, for constellation recovery and transmitter impairment evaluation of dual polarization optical signals with complex modulation formats. Using simulated data, for which transmitter impairments are known exactly, the method is shown to be accurate and robust. In addition, the method is successfully tested on measured QPSK and QAM16 data. Because of its relatively long run-time, the method might best be used for defining and measuring transmitter impairments and for judging the performance of faster constellation recovery methods that rely on serial parameter evaluation rather than optimization. PMID- 27661910 TI - On-chip switch for reconfigurable mode-multiplexing optical network. AB - The switching and routing is essential for an advanced and reconfigurable optical network, and great efforts have been done for traditional single-mode system. We propose and demonstrate an on-chip switch compatible with mode-division multiplexing system. By controlling the induced phase difference, the functionalities of dynamically routing data channels can be achieved. The proposed switch is experimentally demonstrated with low insertion loss of ~1 dB and high extinction ratio of ~20 dB over the C-band for OFF-ON switchover. For further demonstration, the non-return-to-zero on-off keying signals at 10 Gb/s carried on the two spatial modes are successfully processed. Open and clear eye diagrams can be observed and the bit error rate measurements indicate a good data routing performance. PMID- 27661911 TI - Interferometric measurements beyond the coherence length of the laser source. AB - Interferometric measurements beyond the coherence length of the laser are investigated theoretically and experimentally in this paper. Thanks to a high bandwidth detection, high-speed digitizers and a fast digital signal processing, we have demonstrated that the limit of the coherence length can be overcome. Theoretically, the maximal measurable displacement is infinite provided that the sampling rate is sufficiently short to prevent any phase unwrapping error. We could verify experimentally this concept using a miniature interferometer prototype, based on a frequency stabilized vertical cavity surface emitting laser. Displacement measurements at optical path differences up to 36 m could be realized with a relative stability better than 0.1 ppm, although the coherence length estimated from the linewidth and frequency noise measurements do not exceed 6.6 m. PMID- 27661912 TI - Silicon photonic integrated circuits with electrically programmable non-volatile memory functions. AB - Conventional silicon photonic integrated circuits do not normally possess memory functions, which require on-chip power in order to maintain circuit states in tuned or field-configured switching routes. In this context, we present an electrically programmable add/drop microring resonator with a wavelength shift of 426 pm between the ON/OFF states. Electrical pulses are used to control the choice of the state. Our experimental results show a wavelength shift of 2.8 pm/ms and a light intensity variation of ~0.12 dB/ms for a fixed wavelength in the OFF state. Theoretically, our device can accommodate up to 65 states of multi level memory functions. Such memory functions can be integrated into wavelength division mutiplexing (WDM) filters and applied to optical routers and computing architectures fulfilling large data downloading demands. PMID- 27661913 TI - Jitter analysis of timing-distribution and remote-laser synchronization systems. AB - We present a powerful jitter analysis method for timing-distribution and remote laser synchronization systems based on feedback flow between setup elements. We synchronize two different mode-locked lasers in a master-slave configuration locally and remotely over a timing-stabilized fiber link network. Local synchronization reveals the inherent jitter of the slave laser as 2.1 fs RMS (>20 kHz), whereas remote synchronization exhibits an out-of-loop jitter of 8.55 fs RMS integrated for 1 Hz - 1 MHz. Our comprehensive feedback model yields excellent agreement with the experimental results and identifies seven uncorrelated noise sources, out of which the slave laser's jitter dominates with 8.19 fs RMS. PMID- 27661914 TI - Enhanced displacements in reflected beams at hyperbolic metamaterials. AB - We examine the Goos-Hanchen (G-H) shift of a Gaussian beam reflected on a thin slab of Ag/TiO2 hyperbolic multilayer metamaterial (HMM). The HMM is modeled using the effective medium theory which yields the anisotropic dielectric functions of the HMM. The G-H shifts can be very large on the surface of the HMM. It can be about 40 um which are far bigger than the G-H shifts on the usual materials like metals and dielectrics. The enhancement is due to the excitation of the Brewster modes in HMM. Such Brewster modes in HMM have a well-defined frequency-dependent line shape. We relate the the half width at half maximum of the G-H shift to the imaginary part of the complex frequency of the Brewster mode. Moreover, we also present results for the Imbert-Fedorov shifts as well as the spin Hall effect of light on the surface of a thin HMM slab. We show that the spin Hall effect on the HMM slab is much more pronounced than that on the surface of metal. Thus a thin HMM slab can be used to enhance the lateral displacements, which can have many interesting applications for optical devices. PMID- 27661916 TI - Effects of photo-neutralization on the emission properties of quantum dots. AB - In this paper we investigate the coherence properties of a quantum dot used as photon pair source, under two-photon resonant excitation in combination with an additional photo-neutralization laser. The photo-neutralization increases the efficiency of the excitation process and thus, the brightness of the source, by a factor of approximately 1.5 for biexciton-exciton pairs. This enhancement does not degrade the relevant coherences in the system; neither the single photon coherence time, nor the coherence of the excitation process. PMID- 27661917 TI - Kerr effect in multilayer dielectric coatings. AB - We report the utilization of the optical Kerr effect in multilayer dielectric coatings, previously discussed only theoretically. We present the design and realization of multilayer dielectric optical structures with layer-specific Kerr nonlinearities, which permit tailoring of the intensity-dependent effects. The modulation depth in reflectance reaches up to 6% for the demonstrated examples of dielectric nonlinear multilayer coatings. We show that the nonlinearity is based on the optical Kerr effect, with the recovery time faster than the laser pulse envelope of 1 ps. Due to high flexibility in design, the reported dielectric nonlinear multilayer coatings have the potential to open hitherto unprecedented possibilities in nonlinear optics and ultrafast laser applications. PMID- 27661915 TI - All-fiber fourth and fifth harmonic generation from a single source. AB - All-fiber fourth and fifth harmonic generation from a single source is demonstrated experimentally and analyzed theoretically. Light from a fully fiberized high power master oscillator power amplifier is launched into a periodically poled silica fiber generating the second harmonic. The output is then sent through two optical microfibers that generate the third and fourth harmonic, respectively, via four wave mixing (FWM). For a large range of pump wavelengths in the silica optical transmission window, phase matched FWM can be achieved in the microfibers at two different diameters with relatively wide fabrication tolerances of up to +/-5 nm. Our simulations indicate that by optimizing the second harmonic generation efficiency and the diameters and lengths of the two microfibers, conversion efficiencies to the fourth harmonic in excess of 25% are theoretically achievable. PMID- 27661918 TI - Lorentz drift compensation in high harmonic generation in the soft and hard X-ray regions of the spectrum. AB - We present a semi-classical study of the effects of the Lorentz force on electrons during high harmonic generation in the soft and hard X-ray regions driven by near- and mid-infrared lasers with wavelengths from 0.8 to 20 MUm, and at intensities below 1015 W/cm2. The transverse extent of the longitudinal Lorentz drift is compared for both Gaussian focus and waveguide geometries. Both geometries exhibit a longitudinal electric field component that cancels the magnetic Lorentz drift in some regions of the focus, once each full optical cycle. We show that the Lorentz force contributes a super-Gaussian scaling which acts in addition to the dominant high harmonic flux scaling of lambda-(5-6) due to quantum diffusion. We predict that the high harmonic yield will be reduced for driving wavelengths > 6 MUm, and that the presence of dynamic spatial mode asymmetries results in the generation of both even and odd harmonic orders. Remarkably, we show that under realistic conditions, the recollision process can be controlled and does not shut off completely even for wavelengths >10 MUm and recollision energies greater than 15 keV. PMID- 27661919 TI - Picometer-resolution dual-comb spectroscopy with a free-running fiber laser. AB - Dual-comb spectroscopy holds the promise as real-time, high-resolution spectroscopy tools. However, in its conventional schemes, the stringent requirement on the coherence between two lasers requires sophisticated control systems. By replacing control electronics with an all-optical dual-comb lasing scheme, a simplified dual-comb spectroscopy scheme is demonstrated using one dual wavelength, passively mode-locked fiber laser. Pulses with a intracavity dispersion-determined repetition-frequency difference are shown to have good mutual coherence and stability. Capability to resolve the comb teeth and a picometer-wide optical spectral resolution are demonstrated using a simple data acquisition system. Energy-efficient, free-running fiber lasers with a small comb tooth-spacing could enable low-cost dual-comb systems. PMID- 27661920 TI - Suppression of projector distortion in phase-measuring profilometry by projecting adaptive fringe patterns. AB - In phase-measuring profilometry, the lens distortion of commercial projectors may introduce additional bending carrier phase and thus lead to measurement errors. To address this problem, this paper presents an adaptive fringe projection technique in which the carrier phase in the projected fringe patterns is modified according to the projector distortion. After projecting these adaptive fringe patterns, the bending carrier phase induced by the projector distortion is eliminated. Experimental results demonstrate this method to be effective and efficient in suppressing the projector distortion for phase-measuring profilometry. More importantly, this method does not need to calibrate the projector and system parameters, such as the distortion coefficients of the projector and the angle between the optical axes of projector and camera lenses. Hence, it has low computational complexity and enables us to improve the measurement precision for an arbitrary phase-measuring profilometry system. PMID- 27661921 TI - Interferometric control of plasmonic resonator based on polarization-sensitive excitation of surface plasmon polaritons. AB - A plasmonic resonator is proposed whose electromagnetic energy density can be tuned by the polarization state of the incident light. Counter-propagating surface plasmon polaritons, which are excited by polarization-sensitive subwavelength apertures, give tunability. Stored energy density in the resonator varies from the minimum to the maximum when the orientation angle of the incoming electric field rotates by 90 degrees. After optimizing a rectangular cavity and periodic gratings, the on/off ratio is calculated as 430 and measured as 1.55. Based on our scheme, interferometric control is executed simply by rotation of a polarizer. The proposed plasmonic resonator can be utilized in all-optically controlled active plasmonic devices, coherent network elements, particle trapping systems, and polarimeters. PMID- 27661680 TI - Search for Higgs and Z Boson Decays to phigamma with the ATLAS Detector. AB - A search for the decays of the Higgs and Z bosons to a phi meson and a photon is performed with a pp collision data sample corresponding to an integrated luminosity of 2.7 fb^{-1} collected at sqrt[s]=13 TeV with the ATLAS detector at the LHC. No significant excess of events is observed above the background, and 95% confidence level upper limits on the branching fractions of the Higgs and Z boson decays to phigamma of 1.4*10^{-3} and 8.3*10^{-6}, respectively, are obtained. PMID- 27661922 TI - Thermo-optic effects in on-chip lithium niobate microdisk resonators. AB - We report the experimental observation and theoretical analysis of thermo-optic effects in high-Q on-chip lithium-niobate (LN) microdisks. We find that the resonance transmission dip of a LN microdisk was broadened or compressed when the wavelength of the input laser was tuned to the shorter or the longer wavelengths at a wavelength sweeping speed of 4.8 pm/s. When the laser wavelength was shifted with a fast rate (4.8 nm/s), the tendencies of the change in the shape of the transmission dip reverse completely. An oscillatory behavior in the transmission spectra was also observed when the laser wavelength was slowly shifted to the shorter wavelengths. The experimental results were successfully explained by using a theoretical mode considering for a fast thermo-optic effect of LN crystal and a slow heat dissipation process from the LN microdisk to the substrate and surroundings that leads to the reduction of the resonance wavelength through the deformation of the LN microdisk. PMID- 27661923 TI - Simple tunable dual-wavelength fiber laser and multiple self-mixing interferometry to large step height measurement. AB - A simple tunable dual-wavelength fiber laser was developed and multiple self mixing interferometry to large step height measurement was demonstrated. The fiber laser, which can emit two wavelengths without laser mode competition, is composed of a single fiber ring cavity and two fiber branches. Each branch includes a length of erbium-doped fiber and a fiber Bragg grating. Large step heights can be measured using multiple self-mixing interference of the two wavelengths. The maximum height that can be measured is half synthetic wavelength of the two wavelengths. A step height of 2mm constructed with two gauge blocks has been measured. The standard deviation of measurement results is 2.5nm. PMID- 27661924 TI - Direct optical measurements of far- and deep-ultraviolet surface plasmon resonance with different refractive indices. AB - The surface plasmon resonance (SPR) of Al thin films was investigated by varying the refractive index of the environment near the films in the far-ultraviolet (FUV, 120-200 nm) and deep-ultraviolet (DUV, 200-300 nm) regions. An original FUV DUV spectrometer that adopts an attenuated total reflectance (ATR) system was used. The measurable wavelength range was down to the 180 nm, and the environment near the Al surface could be controlled. The resultant spectra enabled the dispersion relationship of Al-SPR in the FUV and DUV regions to be obtained. In the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) on the Al film, the angle and wavelength of the SPR became larger and longer, respectively, compared to those in air. These shifts correspond well with the results of simulations performed using Fresnel equations. PMID- 27661925 TI - Development of regenerated fiber Bragg grating sensors with long-term stability. AB - The effect of annealing cycle on regeneration efficiency was investigated through isothermal treatments between 700 and 1000 degrees C. We determined an inverse relationship between the recovery rate of the peak reflectivity and temperature. A regeneration efficiency of 85.2% and long-term stability at 1000 degrees C for 500 hours were achieved via a slow regeneration process. Thermal sensors developed by isothermal regeneration were determined to be reliable up to 1000 degrees C (+/-2 degrees C). Experimental findings suggest the involvement of both diffusion related phenomena and stress variation through densification of the fiber core in type-I FBG during the thermal regeneration process. PMID- 27661932 TI - Population transfer driven by far-off-resonant fields. AB - For a two-level system, it is believed that a far-off-resonant driving cannot help coherent population transfer between two states. In this work, we propose a scheme to implement the coherent transfer with far-off-resonant driving. The scheme works well with both constant driving and Gaussian driving. The total time to finish population transfer is also minimized by optimizing the detuning and coupling constants. We find that the scheme is sensitive to spontaneous emission much more than dephasing. It might find potential applications in X-ray quantum optics and population transfer in Rydberg atoms as well. PMID- 27661928 TI - Measurement of the profiles of disorder-induced localized resonances in photonic crystal waveguides by local tuning. AB - Near the band edge of photonic crystal waveguides, localized modes appear due to disorder. We demonstrate a new method to elucidate spatial profile of the localized modes in such systems using precise local tuning. Using deconvolution with the known thermal profile, the spatial profile of a localized mode with quality factor (Q) > 105 is successfully reconstructed with a resolution of 2.5 MUm. PMID- 27661931 TI - Gamow vectors explain the shock profile. AB - The description of shock waves beyond the shock point is a challenge in nonlinear physics and optics. Finding solutions to the global dynamics of dispersive shock waves is not always possible due to the lack of integrability. Here we propose a new method based on the eigenstates (Gamow vectors) of a reversed harmonic oscillator in a rigged Hilbert space. These vectors allow analytical formulation for the development of undular bores of shock waves in a nonlinear nonlocal medium. Experiments by a photothermal induced nonlinearity confirm theoretical predictions: the undulation period as a function of power and the characteristic quantized decays of Gamow vectors. Our results demonstrate that Gamow vectors are a novel and effective paradigm for describing extreme nonlinear phenomena. PMID- 27661930 TI - Attosecond pulse generation with an optimization loop in a light-field synthesizer. AB - We developed an efficient, tailored optimization method for attopulse generation using a light-field-synthesizer [M. Hassan et al., Nature 530, 66 (2016)]. We adapted genetic optimization of single-cycle and sub-cycle waveforms to attosecond pulse generation and achieved significantly improved convergence to many target attosecond pulse shapes. Importantly, we show that the single-atom approach (based on strong field approximation) gives similar results to the more complex and numerically intensive 3D model of the attopulse generation process and that spectrally tunable attosecond pulses can be produced with a light-field synthesizer. PMID- 27661926 TI - Displacement measurement using an optoelectronic oscillator with an intra-loop Michelson interferometer. AB - We report on measurement of small displacements with sub-nanometer precision using an optoelectronic oscillator (OEO) with an intra-loop Michelson interferometer. In comparison with conventional homodyne and heterodyne detection methods, where displacement appears as a power change or a phase shift, respectively, in the OEO detection, the displacement produces a shift in the oscillation frequency. In comparison with typical OEO sensors, where the frequency shift is proportional to the OEO oscillation frequency in radio frequency domain, the frequency shift in our method with an intra-loop interferometer is proportional to an optical frequency. We constructed a hybrid apparatus and compared characteristics of the OEO and heterodyne detection methods. PMID- 27661933 TI - Roll-off factor dependence of Nyquist pulse transmission. AB - We evaluate the dependence of system performance on the roll-off factor, alpha, of a Nyquist pulse in a single-channel 1.28 Tbit/s-525 km transmission both experimentally and analytically. Low alpha values are preferable in terms of spectral efficiency and tolerance to chromatic dispersion and polarization-mode dispersion, while a strong overlap with neighboring symbols results in larger nonlinear impairments. On the other hand, a Nyquist pulse with high alpha values also suffers from nonlinearity due to higher peak power. As a result, we found experimentally that the optimum alpha value is 0.4~0.6, which agrees well with the analysis. PMID- 27661929 TI - Origin of terminal voltage variations due to self-mixing in terahertz frequency quantum cascade lasers. AB - We explain the origin of voltage variations due to self-mixing in a terahertz (THz) frequency quantum cascade laser (QCL) using an extended density matrix (DM) approach. Our DM model allows calculation of both the current-voltage (I-V) and optical power characteristics of the QCL under optical feedback by changing the cavity loss, to which the gain of the active region is clamped. The variation of intra-cavity field strength necessary to achieve gain clamping, and the corresponding change in bias required to maintain a constant current density through the heterostructure is then calculated. Strong enhancement of the self mixing voltage signal due to non-linearity of the (I-V) characteristics is predicted and confirmed experimentally in an exemplar 2.6 THz bound-to-continuum QCL. PMID- 27661927 TI - Laser induced ultrasonic phased array using full matrix capture data acquisition and total focusing method. AB - Laser ultrasonics is a technique where lasers are employed to generate and detect ultrasound. A data collection method (full matrix capture) and a post processing imaging algorithm, the total focusing method, both developed for ultrasonic arrays, are modified and used in order to enhance the capabilities of laser ultrasonics for nondestructive testing by improving defect detectability and increasing spatial resolution. In this way, a laser induced ultrasonic phased array is synthesized. A model is developed and compared with experimental results from aluminum samples with side drilled holes and slots at depths of 5 - 20 mm from the surface. PMID- 27661934 TI - Correlation steering in the angularly multimode Raman atomic memory. AB - We present the possibility of steering the direction of correlations between the off-resonant Raman scattered photons from the angularly multimode atomic memory based on warm rubidium vapors. Using acousto-optic deflectors (AOD) driven by different modulation frequencies, we experimentally change the angle of incidence of the laser beams on the atomic ensemble. By performing correlation measurements for various deflection angles, we verify that we can choose the anti-Stokes light propagation direction independently of the correlated Stokes scattered light in a continuous way. As a result we can select the spatial mode of photons retrieved from the memory, which may be important for future development of quantum information processing. PMID- 27661935 TI - Fault-tolerant and finite-error localization for point emitters within the diffraction limit. AB - We implement a self-interference technique for determining the separation between two incoherent point sources. This method relies on image inversion interferometry and when used with the appropriate data analytics, it yields an estimate of the separation with finite-error, including the case when the sources overlap completely. The experimental results show that the technique has a good tolerance to noise and misalignment, making it an interesting consideration for high resolution instruments in microscopy or astronomy. PMID- 27661936 TI - Influence of detector noise in holographic imaging with limited photon flux. AB - Lensless coherent diffractive imaging usually requires iterative phase-retrieval for recovering the missing phase information. Holographic techniques, such as Fourier-transform holography (FTH) or holography with extended references (HERALDO), directly provide this phase information and thus allow for a direct non-iterative reconstruction of the sample. In this paper, we analyze the effect of detector noise on the reconstruction for FTH and HERALDO with linear and rectangular references. We find that HERALDO is more sensitive to this type of noise than FTH, especially if rectangular references are employed. This excessive noise, caused by the necessary differentiation step(s) during reconstruction in case of HERALDO, additionally depends on the numerical implementation. When considering both shot-noise and detector noise, we find that FTH provides a better signal-to-noise ratio (SNR) than HERALDO if the available photon flux from the light source is low. In contrast, at high photon flux HERALDO provides better SNR and resolution than FTH. Our findings will help in designing optimum holographic imaging experiments particularly in the photon-flux-limited regime where most ultrafast experiments operate. PMID- 27661937 TI - Polymer lasers assembled by suspending membranes on a distributed feedback grating. AB - Polymer lasers are fabricated by an assembly method. A polymer membrane is directly attached on the one- or two- dimensional grating. The suspended membrane acts as an active waveguide, which is supported by the grating ridge, leaving air gaps in the grating valley. Most of the radiation is effectively confined within the active waveguide due to the strong reflection at the membrane/air interfaces. So, low threshold lasing can be achieved when the sample is optically pumped. This fabrication method provides an alternative to investigate low-threshold polymer lasers. PMID- 27661938 TI - Analysis and reduction of errors caused by Poisson noise for phase diversity technique. AB - An effective method for reducing the sensitivity of phase diversity (PD) technique to Poisson noise is proposed. The denoising algorithm based on blocking matching and 3D filtering is first introduced in the wavefront sensing field as a preprocessing stage. Then, the PD technique is applied to the denoised images. Results of the numerical simulations and experiments demonstrate that our approach is better than the traditional PD technique in terms of both the root mean-square error (RMSE) of phase estimates and the structural similarity index metrics (SSIM). The RMSEs of phase estimates on synthetic data are decreased by approximately 40% across noise levels within the range of 58.7-18.8 dB in terms of peak signal-to-noise ratio (PSNR). Meanwhile, the overall decline range of SSIM is significantly decreased from 49% to 9%. The experiment and simulation results are in good agreement. The approach may be widely used in various domains, such as the measurements of intrinsic aberrations in optical systems and compensations for atmospheric turbulence. PMID- 27661939 TI - Wavelength tunable integrated add-drop filter with 10.6 nm bandwidth adjustability. AB - We present the design and characterization of a silicon-on-insulator based bandwidth and wavelength-tunable add-drop filter. The tunability of the device is achieved by independently controlling the central wavelength of two cascaded contra-directional grating assisted couplers. The device was fabricated using e beam lithography and the tuning is demonstrated using the thermo-optic effect, which was obtained with metal heaters fabricated by a lift-off process. It is experimentally demonstrated that within the wavelength range of 1555 nm to 1573 nm the transmission bandwidth of the device can be tuned from 1.1 nm to 11.7 nm. Moreover, more than 4 nm of central wavelength tuning is demonstrated. The tunability of the central wavelength is limited by the breakdown current of the metal heaters. PMID- 27661940 TI - Optical zooming based on focusing grating in direct drive ICF. AB - In direct drive ICF, optical zooming is an effective way to mitigate cross-beam energy transfer and increase the hydrodynamic efficiency, by reducing the spot size of the laser beams while target compressing. In this paper, a novel optical zooming scheme is proposed, which employs a focusing grating to focus the broadband laser pulse, changing the spot size on the target within single beamlet. Experimentally, a focusing grating with clean aperture of 40-mm * 40-mm placed after the collimated light successfully realized the peak-valley of defocusing wavefront distribution of 0.73 um as the wavelength ranging from 1052.43 nm to 1053.23 nm. Extended to the full-sized focusing grating with laser beam of 360-mm * 360-mm, it is derived that the focal spot reduction reaches to 21.8% with the 3rd harmonic light ranging from 350.81 nm to 351.08 nm, decreasing from 375 um to 294 um with 300 um shaping continuous phase plate. PMID- 27661941 TI - Versatile and tunable surface plasmon polariton excitation over a broad bandwidth with a simple metaline by external polarization modulation. AB - Surface plasmon polariton (SPP) sources and launchers are highly demanded in various applications of nanophotonics. Here, we propose a general approach that can realize complete control of the complex extinction ratio (including amplitude and phase) of any two linearly independent SPP modes excited by any elementary SPP excitation architecture just by manipulating the incident polarization state. In an optical system, it suffices to simply tune the orientation angles of a linear polarizer and a quarter wave plate, which may greatly simplify the design and application of SPP launchers and diversify their functionalities. As an example to show the broad application prospect of this method, we design and realize a metaline consisting of Delta-shaped plasmonic nanoantennas, which can effectively realize dual functionalities, i.e., the tunable directional SPP excitation at an arbitrarily chosen wavelength and the complete unidirectional SPP excitation over a broad bandwidth. This general approach can also be extended to the control of the complex extinction ratio of any two linearly independent excited modes in many other linear optical systems, such as two modes in a waveguide or two diffraction orders in a grating, over a broad bandwidth. PMID- 27661942 TI - Wavefront shaping for imaging-based flow velocity measurements through distortions using a Fresnel guide star. AB - Imaging-based flow measurement techniques, like particle image velocimetry (PIV), are vulnerable to time-varying distortions like refractive index inhomogeneities or fluctuating phase boundaries. Such distortions strongly increase the velocity error, as the position assignment of the tracer particles and the decrease of image contrast exhibit significant uncertainties. We demonstrate that wavefront shaping based on spatially distributed guide stars has the potential to significantly reduce the measurement uncertainty. Proof of concept experiments show an improvement by more than one order of magnitude. Possible applications for the wavefront shaping PIV range from measurements in jets and film flows to biomedical applications. PMID- 27661943 TI - 320 Gbit/s, 20 Gsymbol/s 256 QAM coherent transmission over 160 km by using injection-locked local oscillator. AB - We demonstrate 20 Gsymbol/s, 256 QAM polarization multiplexed (pol-mux) 320 Gbit/s coherent transmission. By employing an LD-based injection locking circuit, we achieved low noise optical carrier-phase locking between the LO and the data signal. Furthermore, frequency domain equalization and digital back-propagation enabled us to realize precise compensation for transmitted waveform distortions. As a result, a 320 Gbit/s data was successfully transmitted over 160 km with a potential spectral efficiency of 10.9 bit/s/Hz. This is the highest symbol rate yet achieved in a pol-mux 256 QAM coherent transmission. In addition, we also describe a pol-mux 256 QAM transmission at a symbol rate of 10 Gsymbol/s. PMID- 27661944 TI - Spatially incoherent off-axis Fourier holography without using spatial light modulator (SLM). AB - We present a spatially incoherent dual path Fourier holographic system. Conceptually it is similar to Fourier incoherent single channel holography (FISCH). Although our incoherent off-axis Fourier holographic (IOFH) system does not have the robustness of a single channel system, it has three advantages over FISCH, with two being quite obvious from setup. First, no SLM is required, thus making the system simple and cost-effective. Second, it is capable of high light throughput because in FISCH, the use of SLM reduces light intensity in half by splitting one beam into two; furthermore, an analyzer is required to create interference which also reduces light intensity. The third advantage, which makes this IOFH system applicable even for on-axis samples (as opposed to samples in a half plane as is necessary for FISCH), is achieved by tilting one mirror. Here we demonstrate our system with a sample in half plane as in FISCH for different axial positions, and then by placing the object on an optical axis and tilting one mirror. The reconstructed images demonstrate holographic capabilities of our IOFH system for both on-axis and half plane sample locations. PMID- 27661945 TI - Detection of trace organics in Martian soil analogs using fluorescence-free surface enhanced 1064-nm Raman Spectroscopy. AB - A significant technology challenge in planetary missions is the in situ detection of organics at the sub-part-per-million (ppm) level in soils. This article reports the organic compound detection in Mars-like soils at the sub-ppm level using an ultra-sensitive spectral sensing technique based on fluorescence-free surface-enhanced Raman scattering (SERS), which has a significantly improved sensitivity and reduced fluorescence noise. Raman spectral detection of ppm level organics in Antarctic Dry Valley and Mojave Desert soils have been obtained for the first time, which otherwise are not detected by other Raman spectral techniques. PMID- 27661946 TI - Precise and fast spatial-frequency analysis using the iterative local Fourier transform. AB - The use of the discrete Fourier transform has decreased since the introduction of the fast Fourier transform (fFT), which is a numerically efficient computing process. This paper presents the iterative local Fourier transform (ilFT), a set of new processing algorithms that iteratively apply the discrete Fourier transform within a local and optimal frequency domain. The new technique achieves 210 times higher frequency resolution than the fFT within a comparable computation time. The method's superb computing efficiency, high resolution, spectrum zoom-in capability, and overall performance are evaluated and compared to other advanced high-resolution Fourier transform techniques, such as the fFT combined with several fitting methods. The effectiveness of the ilFT is demonstrated through the data analysis of a set of Talbot self-images (1280 * 1024 pixels) obtained with an experimental setup using grating in a diverging beam produced by a coherent point source. PMID- 27661947 TI - Motion artefact detection in structured illumination microscopy for live cell imaging. AB - The reconstruction process of structured illumination microscopy (SIM) creates substantial artefacts if the specimen has moved during the acquisition. This reduces the applicability of SIM for live cell imaging, because these artefacts cannot always be recognized as such in the final image. A movement is not necessarily visible in the raw data, due to the varying excitation patterns and the photon noise. We present a method to detect motion by extracting and comparing two independent 3D wide-field images out of the standard SIM raw data without needing additional images. Their difference reveals moving objects overlaid with noise, which are distinguished by a probability theory-based analysis. Our algorithm tags motion-artefacts in the final high-resolution image for the first time, preventing the end-user from misinterpreting the data. We show and explain different types of artefacts and demonstrate our algorithm on a living cell. PMID- 27661948 TI - 340 nm pulsed UV LED system for europium-based time-resolved fluorescence detection of immunoassays. AB - We report on the design, development and investigation of an optical system based on UV light emitting diode (LED) excitation at 340 nm for time-resolved fluorescence detection of immunoassays. The system was tested to measure cardiac marker Troponin I with a concentration of 200 ng/L in immunoassay. The signal-to noise ratio was comparable to state-of-the-art Xenon flash lamp based unit with equal excitation energy and without overdriving the LED. We performed a comparative study of the flash lamp and the LED based system and discussed temporal, spatial, and spectral features of the LED excitation for time-resolved fluorimetry. Optimization of the suggested key parameters of the LED promises significant increase of the signal-to-noise ratio and hence of the sensitivity of immunoassay systems. PMID- 27661949 TI - Slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow. AB - Three-dimensional cellular imaging techniques have become indispensable tools in biological research and medical diagnostics. Conventional 3D imaging approaches employ focal stack collection to image different planes of the cell. In this work, we present the design and fabrication of a slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow. The approach employs slanted microfluidic channels fabricated in glass using ultrafast laser inscription. The slanted nature of the microfluidic channels ensures that samples come into and go out of focus, as they pass through the microscope imaging field of view. This novel approach enables the collection of focal stacks in a straight-forward and automated manner, even with off-the-shelf microscopes that are not equipped with any motorized translation/rotation sample stages. The presented approach not only simplifies conventional focal stack collection, but also enhances the capabilities of a regular widefield fluorescence microscope to match the features of a sophisticated confocal microscope. We demonstrate the retrieval of sectioned slices of microspheres and cells, with the use of computational algorithms to enhance the signal-to-noise ratio (SNR) in the collected raw images. The retrieved sectioned images have been used to visualize fluorescent microspheres and bovine sperm cell nucleus in 3D while using a regular widefield fluorescence microscope. We have been able to achieve sectioning of approximately 200 slices per cell, which corresponds to a spatial translation of ~ 15 nm per slice along the optical axis of the microscope. PMID- 27661950 TI - Detector-decoy high-dimensional quantum key distribution. AB - The decoy-state high-dimensional quantum key distribution provides a practical secure way to share more private information with high photon-information efficiency. In this paper, based on detector-decoy method, we propose a detector decoy high-dimensional quantum key distribution protocol. Employing threshold detectors and a variable attenuator, we can promise the security under Gsussian collective attacks with much simpler operations in practical implementation. By numerical evaluation, we show that without varying the source intensity, our protocol performs much better than one-decoy-state protocol and as well as the two-decoy-state protocol in the infinite-size regime. In the finite-size regime, our protocol can achieve better results. Specially, when the detector efficiency is lower, the advantage of the detector-decoy method becomes more prominent. PMID- 27661951 TI - All-optical controlling based on nonlinear graphene plasmonic waveguides. AB - We give the effective refractive index of graphene plasmonic waveguides with both linear and nonlinear effects based on the nonlinear cross-phase modulation, and address the effects of photo-induced refractive index change and absorption change. A non-resonant all-optical nonlinear graphene plasmonic switch with an ultra-compact size of 0.25 MUm2 is proposed and numerically analyzed based on the dynamics of the photo-induced absorption change. The results show that the all-optical graphene plasmonic switch can realize a broad bandwidth over 5 THz, a potentially very high switching speed and an extinction ratio of 18.14 dB with the electric amplitude of the pump light of 1.5 * 107 V/m at the signal frequency of 28 THz. Our study could provide a possibility for future all-optical highly integrated optical components. PMID- 27661952 TI - Liquid microlenses and waveguides from bulk nematic birefringent profiles. AB - We demonstrate polarization-selective microlensing and waveguiding of laser beams by birefringent profiles in bulk nematic fluids using numerical modelling. Specifically, we show that radial escaped nematic director profiles with negative birefringence focus and guide light with radial polarization, whereas the opposite - azimuthal - polarization passes through unaffected. A converging lens is realized in a nematic with negative birefringence, and a diverging lens in a positive birefringence material. Tuning of such single-liquid lenses by an external low-frequency electric field and by adjusting the profile and intensity of the beam itself is demonstrated, combining external control with intrinsic self-adaptive focusing. Escaped radial profiles of birefringence are shown to act as single-liquid waveguides with a single distinct eigenmode and low attenuation. Finally, this work is an approach towards creating liquid photonic elements for all-soft matter photonics. PMID- 27661953 TI - Synchronized self-mode-locked 1061-nm and 1064-nm monolithic Nd:YAG laser at cryogenic temperatures with two orthogonally polarized emissions: generation of 670 GHz beating. AB - A dual-wavelength self-mode-locked monolithic Nd:YAG laser at 1061 and 1064 nm is realized at cryogenic temperatures. At an incident pump power of 5.5 W, the total output power can reach 2.5 W and the mode-locked pulse width is 29 ps at a pulse repetition rate of 7.75 GHz. The synchronization of the dual-wavelength emissions leads to a beat frequency of 670 GHz in the individual mode-locked pulse. It is further discovered that the laser output consists of two orthogonally polarized components with a central frequency difference of 127 MHz. The central frequency difference between two orthogonal polarizations mainly arises from the external mechanical stress introduced by the copper holder for the laser crystal. PMID- 27661954 TI - Photonic integrated circuits unveil crisis-induced intermittency. AB - We experimentally investigate an intermittent route to chaos in a photonic integrated circuit consisting of a semiconductor laser with time-delayed optical feedback from a short external cavity. The transition from a period-doubling dynamics to a fully-developed chaos reveals a stage intermittently exhibiting these two dynamics. We unveil the bifurcation mechanism underlying this route to chaos by using the Lang-Kobayashi model and demonstrate that the process is based on a phenomenon of attractor expansion initiated by a particular distribution of the local Lyapunov exponents. We emphasize on the crucial importance of the distribution of the steady-state solutions introduced by the time-delayed feedback on the existence of this intermittent dynamics. PMID- 27661955 TI - Transverse single-shot cross-correlation scheme for laser pulse temporal measurement via planar second harmonic generation. AB - We present a novel single-shot cross-correlation technique based on the analysis of the transversally emitted second harmonic generation in crystals with random distribution and size of anti-parallel nonlinear domains. We implement it to the measurement of ultrashort laser pulses with unknown temporal duration and shape. We optimize the error of the pulse measurement by controlling the incident angle and beam width. As novelty and unlike the other well-known cross correlation schemes, this technique can be implemented for the temporal characterization of pulses over a very wide dynamic range (30 fs-1ps) and wavelengths (800-2200 nm), using the same crystal and without critical angular or temperature alignment. PMID- 27661956 TI - Broadband near total light absorption in non-PT-symmetric waveguide-cavity systems. AB - We introduce broadband waveguide absorbers with near unity absorption. More specifically, we propose a compact non-parity-time-symmetric perfect absorber unit cell, consisting of two metal-dielectric-metal (MDM) stub resonators with unbalanced gain and loss side-coupled to a MDM waveguide, based on unidirectional reflectionlessness at exceptional points. With proper design, light can transport through the perfect absorber unit cell with reflection close to zero in a broad wavelength range. By cascading multiple unit cell structures, the overall absorption spectra are essentially the superposition of the absorption spectra of the individual perfect absorber unit cells, and absorption of ~ 100% is supported in a wide range of frequencies. PMID- 27661957 TI - Etalon filters for Brillouin microscopy of highly scattering tissues. AB - Brillouin imaging of turbid biological tissues requires an effective rejection of the background noise due to elastic scattering of probe laser light. We have developed a narrowband spectral notch filter based on a pair of a free-space Fabry-Perot etalon and a mirror. The etalon filter in a 4-pass configuration is able to suppress elastically-scattered laser light with a high extinction ratio of > 40 dB and transmit inelastically-scattered light in a frequency shift range of 2-14 GHz with only 2 dB insertion loss. We also describe a simple etalon that enables us to use semiconductor diode laser sources for Brillouin microscopy by removing spontaneous emission noise. Using a clinically-viable Brillouin microscope employing these filters, we demonstrate the first Brillouin confocal imaging of the sclera and conjunctiva of the porcine eye. PMID- 27661958 TI - Multi-function Mach-Zehnder modulator for pulse shaping and generation. AB - We present a multi-function electronic-photonic integrated circuit (EPIC) design which exploits a new operation mode of a Mach-Zehnder modulator (MZM). Different from the conventional design, the two arms of the modulator are driven by time shifted signals of tunable amplitude. We study its operation in the linear and quadratic regions where the MZM is biased at pi/2 and pi initial phase difference, respectively. In the linear region, the modulator sums the waveforms of the driving signals in the two arms, which can be used to add pre-emphasis function to the modulator, and hence it obviates an electrical pre-emphasis driver. Furthermore, when operating in the quadratic region, the modulator can produce optical pulses with tunable pulse width at double clock rate. Prototype circuits are designed first using a suit of device, electromagnetic simulators to build compact models, and then importing into a photonic circuit simulator for complete circuit performance evaluation. PMID- 27661959 TI - Low-noise quantum frequency down-conversion of indistinguishable photons. AB - We present experimental results on quantum frequency down-conversion of indistinguishable single photons emitted by an InAs/GaAs quantum dot at 904 nm to the telecom C-band at 1557 nm. Hong-Ou-Mandel (HOM) interference measurements are shown prior to and after the down-conversion step. We perform Monte-Carlo simulations of the HOM experiments taking into account the time delays of the different interferometers used and the signal-to-background ratio and further estimate the impact of spectral diffusion on the degree of indistinguishability. By that we conclude that the down-conversion step does not introduce any loss of HOM interference visibility. A noise-free conversion-process along with a high conversion-efficiency (> 30 %) emphasize that our scheme is a promising candidate for an efficient source of indistinguishable single photons at telecom wavelengths. PMID- 27661960 TI - Combined Yb/Nd driver for optical parametric chirped pulse amplifiers. AB - We report on the developed front-end/pump system for optical parametric chirped pulse amplifiers. The system is based on a dual output fiber oscillator/power amplifier which seeds and assures all-optical synchronization of femtosecond Yb and picosecond Nd laser amplifiers operating at a central wavelength of 1030 nm and 1064 nm, respectively. At the central wavelength of 1030 nm, the fiber oscillator generates partially stretched 4 ps pulses with the spectrum supporting a <120 fs pulse duration and pulse energy of 0.45 nJ. The energy of generated 1064 nm pulses is 0.15 nJ, which is sufficient for the efficient seeding of high contrast Nd:YVO chirped pulse regenerative amplifier/post amplifier systems generating 9 mJ pulses compressible to 16 ps duration. The power amplification stages, based on Nd:YAG crystals, provide 62 mJ pulses compressible to 20 ps pulse duration at a repetition rate of 1 kHz. Further energy scaling currently is prevented by limited dimensions of the diffraction gratings, which, because of the fast progress in MLD grating manufacturing technologies is only a temporary obstacle. PMID- 27661961 TI - Optical bistability in core-shell magnetoplasmonic nanoparticles with magnetocontrollability. AB - We propose a mechanism to actively tune optical bistable behavior with the external magnetic field in nonlinear coated nanospheres with a magneto-optical (MO) shell and nonlinear metallic core. We show that such nanostructures can exhibit typical bistable phenomena near surface plasmon resonant wavelengths, which can be modified through the external magnetic fields B. We demonstrate numerically that the optical bistability exists only when the volume fraction eta of the metallic core is larger than a critical one etac. Moreover, the bistable behavior is found to be dependent on the incident polarization state as well as the external magnetic field. The application of an external magnetic field does not only increase (or decrease) the upper/lower threshold fields but also changes the critical volume fractions. Such nanostructures with magneto controllable optical bistability may be designed for us as nonlinear optical nanodevices, such as optical nanoswitches, nanosensors and so on. PMID- 27661962 TI - Unscented Kalman filters for polarization state tracking and phase noise mitigation. AB - Simultaneous polarization and phase noise tracking and compensation is proposed based on an unscented Kalman filter (UKF). We experimentally demonstrate the tracking under noise-loading and after 800-km single-mode fiber transmission with 20-Gbaud QPSK and 16-QAM signals. These experiments show that the proposed UKF outperforms both conventional blind tracing algorithms and a previously proposed extended Kalman filter, at the cost of higher complexity. Additionally, we propose and test modified Kalman filter algorithms to reduce computational complexity. PMID- 27661963 TI - Low drift cw-seeded high-repetition-rate optical parametric amplifier for fingerprint coherent Raman spectroscopy. AB - We introduce a broadly tunable robust source for fingerprint (170 - 1620 cm 1) Raman spectroscopy. A cw thulium-doped fiber laser seeds an optical parametric amplifier, which is pumped by a 7-W, 450-fs Yb:KGW bulk mode-locked oscillator with 41 MHz repetition rate. The output radiation is frequency doubled in a MgO:PPLN crystal and generates 0.7 - 1.3-ps-long narrowband pump pulses that are tunable between 885 and 1015 nm with >80 mW average power. The Stokes beam is delivered by a part of the oscillator output, which is sent through an etalon to create pulses with 1.7 ps duration. We demonstrate a stimulated Raman gain measurement of toluene in the fingerprint spectral range. The cw seeding intrinsically ensures low spectral drift. PMID- 27661964 TI - Real time dynamic strain monitoring of optical links using the backreflection of live PSK data. AB - A major cause of faults in optical communication links is related to unintentional third party intrusions (normally related to civil/agricultural works) causing fiber breaks or cable damage. These intrusions could be anticipated and avoided by monitoring the dynamic strain recorded along the cable. In this work, a novel technique is proposed to implement real-time distributed strain sensing in parallel with an operating optical communication channel. The technique relies on monitoring the Rayleigh backscattered light from optical communication data transmitted using standard modulation formats. The system is treated as a phase-sensitive OTDR (PhiOTDR) using random and non periodical non-return-to-zero (NRZ) phase-shift keying (PSK) pulse coding. An I/Q detection unit allows for a full (amplitude, phase and polarization) characterization of the backscattered optical signal, thus achieving a fully linear system in terms of PhiOTDR trace coding/decoding. The technique can be used with different modulation formats, and operation using 4 Gbaud single polarization dual PSK and 4 Gbaud dual-polarization quadrature PSK is demonstrated. As a proof of concept, distributed sensing of dynamic strain with a sampling of 125 kHz and a spatial resolution of 2.5 cm (set by the bit size) over 500 m is demonstrated for applied sinusoidal strain signals of 500 Hz. The limitations and possibilities for improvement of the technique are also discussed. PMID- 27661965 TI - Broadband terahertz dispersion control in hybrid waveguides. AB - Dispersion control is a key objective in the field of photonics and spectroscopy, since it enhances non-linear effects by both enabling phase matching and offering slow light generation. In addition, it is essential for frequency comb generation, which requires a phase-lock mechanism that is provided by broadband compensation of group velocity dispersion (GVD). At optical frequencies, there are several well-established concepts for dispersion control such as prism or grating pairs. However, terahertz dispersion control is still a challenge, thus hindering further progress in the field of terahertz science and technology. In this work, we present a hybrid waveguide with both broadband, tuneable positive and more than octave-spanning negative terahertz GVD on the order of 10 22 s2/m, which is suitable for either intra- or extra cavity operation. This new terahertz device will enable ultra-short pulse compression, allow soliton propagation, improve frequency comb operation and foster the development of novel non-linear applications. PMID- 27661967 TI - More Accurate Method to Evaluate the Performance of Scores in Outcomes Prediction. PMID- 27661966 TI - Brain Targeting of Temozolomide via the Intranasal Route Using Lipid-Based Nanoparticles: Brain Pharmacokinetic and Scintigraphic Analyses. AB - The aim of the present work was to investigate the efficacy of temozolomide nanostructured lipid carriers (TMZ-NLCs) to enhance brain targeting via nasal route administration. The formulation was optimized by applying a four-factor, three-level Box-Behnken design. The developed formulations and the functional relationships between their independent and dependent variables were observed. The independent variables used in the formulation were gelucire (X1), liquid lipid/total lipid (X2), Tween 80 (X3), and sonication time (X4), and their effects were observed with regard to size (Y1), % drug release (Y2), and drug loading (Y3). The optimized TMZ-NLC was further evaluated for its surface morphology as well as ex vivo permeation and in vivo studies. All TMZ-NLC formulations showed sizes in the nanometer range, with high drug loading and prolonged drug release. The optimized formulation (TMZ-NLCopt) showed an entrapment efficiency of 81.64 +/- 3.71%, zeta potential of 15.21 +/- 3.11 mV, and polydispersity index of less than 0.2. The enhancement ratio was found to be 2.32-fold that of the control formulation (TMZ-disp). In vivo studies in mice showed that the brain/blood ratio of TMZ-NLCopt was found to be significantly higher compared to that of TMZ-disp (intranasal, intravenous). Scintigraphy images of mouse brain showed the presence of a high concentration of TMZ. The AUC ratio of TMZ-NLCopt to TMZ-disp in the brain was the highest among the organs. The findings of this study substantiate the existence of a direct nose-to-brain delivery route for NLCs. PMID- 27661968 TI - A Real-World Evaluation of Repeat Paracentesis-guided Management of Spontaneous Bacterial Peritonitis. AB - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common infection in cirrhosis associated with high mortality. More than 20% of patients with SBP do not respond to initial antibiotics. Guidelines differ in recommendations to repeat paracentesis (retap) to confirm antibiotic efficacy. We aim to evaluate the effect of retap-guided management of SBP on antibiotic escalation and 30-day transplant-free survival. MATERIALS AND METHODS: Retrospective cohort study of cirrhotic patients with SBP admitted to a single transplant center from 2010 to 2014. Patients were divided into 2 groups: retap-guided management versus no retap. Prevalence of initial antibiotic treatment failure, defined as <25% decrease in ascitic polymorphonuclear cells, and factors associated with treatment failure, antibiotic escalation and 30-day transplant-free survival were evaluated. RESULTS: Out of 210 patients, 146 (age 58, 74% male, mean model for end-stage liver disease score, 25) had retap and treatment failure was noted in 28 (22%). Gram-positive bacteria accounted for 44% of all positive cultures and third-generation cepahalosporin resistance was noted in 23%. Thirty-day transplant-free survival was 72% and 62% in retap and control groups, respectively (P=0.07). Treatment failure independently doubled the 30-day mortality rate (hazard ratio: 2.15, 1.03 to 4.50, P=0.04). After adjusting for age, model for end-stage liver disease and nosocomial infection, retap-guided management was not associated with improved survival (P=0.34). CONCLUSIONS: The prevalence of initial treatment failure is high (22%) in patients with SBP and doubles the 30-day mortality risk, supporting recommendations to retap all patients with SBP. PMID- 27661969 TI - Gastrointestinal Polyposis in Cowden Syndrome. AB - GOALS: To further characterize the gastrointestinal manifestations of Cowden syndrome in clinically well-annotated patients to improve the diagnosis of this syndrome. BACKGROUND: The gastrointestinal manifestations of Cowden Syndrome, an important heritable and multiorgan cancer syndrome, are not well defined. Proper diagnosis is essential for effective cancer surveillance and prevention in these patients. STUDY: Cowden patients with gastrointestinal polyps were selected for medical record and pathologic slide review. RESULTS: Of 19 total patients, genetic testing revealed pathogenic PTEN mutations in 12. Pan-colonic (11 patients, 58%) and pan-gastrointestinal (8-patients, 42%) polyp distributions were common. Inflammatory (juvenile) polyps were the most common of the hamartomatous polyp (18 patients, 95%), along with expansive lymphoid follicle polyps (12 patients, 63%), ganglioneuromatous polyps (10 patients, 53%), and intramucosal lipomas (5 patients, 26%). The findings of 2 or more hamartomatous polyp types per patient emerged as a newly described and highly prevalent (79%) feature of Cowden syndrome. Ganglioneuromatous polyps, rare in the general population, and intramucosal lipomas, which may be unique to Cowden syndrome, should both prompt further evaluation. Colonic adenomas and adenocarcinomas were common; 10 patients (53%) had single and 3 (16%) had >=3 adenomas, whereas 2 (11%) had colonic adenocarcinoma, strengthening the emerging association of colorectal cancer with Cowden syndrome. CONCLUSIONS: The clinical phenotypes and gastrointestinal manifestations in Cowden syndrome are quite variable but this series adds the following new considerations for this syndromic diagnosis: multiple gastrointestinal hamartomas, especially 2 or more hamartoma types, and any intramucosal lipomas or ganglioneuromas. These features should warrant consideration of Cowden syndrome. PMID- 27661970 TI - Appointment Wait Time, Primary Care Provider Status, and Patient Demographics are Associated With Nonattendance at Outpatient Gastroenterology Clinic. AB - GOALS: We intended to identify the factors associated with missed appointments at a gastroenterology (GI) clinic in an academic setting. BACKGROUND: Missed clinic appointments reduce clinic efficiency, waste resources, and increase costs. Limited data exist on subspecialty clinic attendance. STUDY: We performed a case control study using data from the electronic health record of patients scheduled for an appointment at the adult GI clinic at the Banner University Medical Center between March and October of 2014. Patients who missed their appointment during the study period served as cases. Controls were randomly selected from patients who completed their appointment during the study period. Analysis included univariate and multivariate logistic regression analysis. RESULTS: Of 2331 scheduled clinic appointments, 195 (8.4%) were missed appointments. Longer waiting time from referral to scheduled appointment was significantly associated with missed appointment (AOR=1.014; 95% CI, 1.01-1.02; P<0.001). Patients with primary care providers (PCPs) were less likely to miss their appointment than those without PCPs (AOR=0.35; 95% CI, 0.18-0.66; P=0.001). Among patient demographic characteristics, ethnicity and marital status were associated with missed appointment. CONCLUSIONS: Wait time, ethnicity, marital status, and PCP status were associated with missed GI clinic appointments. Further investigations are needed to assess the effects of intervention strategies directed at reducing appointment wait time and increasing PCP-based care. PMID- 27661971 TI - Acknowledgements Upon the Changing of the Guard. PMID- 27661972 TI - Jackhammer Esophagus Based on the New Chicago Classification. PMID- 27661973 TI - Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma. AB - BACKGROUND & GOALS: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. METHODS: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG<=6), HS-2 (612 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. CONCLUSIONS: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC. PMID- 27661974 TI - Vanishing Bile Ducts, Cholesatatic Jaundice and Portal Hypertension Secondary to Hepatic ALECT-2 Amyloid Deposition. PMID- 27661976 TI - The Severity of Symptoms Related to Irritable Bowel Syndrome is a Risk Factor for the Misclassification of Significant Organic Disease. PMID- 27661977 TI - Role of Reversible Histidine Coordination in Hydroxylamine Reduction by Plant Hemoglobins (Phytoglobins). AB - Reduction of hydroxylamine to ammonium by phytoglobin, a plant hexacoordinate hemoglobin, is much faster than that of other hexacoordinate hemoglobins or pentacoordinate hemoglobins such as myoglobin, leghemoglobin, and red blood cell hemoglobin. The reason for differences in reactivity is not known but could be intermolecular electron transfer between protein molecules in support of the required two-electron reduction, hydroxylamine binding, or active site architecture favoring the reaction. Experiments were conducted with phytoglobins from rice, tomato, and soybean along with human neuroglobin and soybean leghemoglobin that reveal hydroxylamine binding as the rate-limiting step. For hexacoordinate hemoglobins, binding is limited by the dissociation rate constant for the distal histidine, while leghemoglobin is limited by an intrinsically low affinity for hydroxylamine. When the distal histidine is removed from rice phytoglobin, a hydroxylamine-bound intermediate is formed and the reaction rate is diminished, indicating that the distal histidine imidazole side chain is critical for the reaction, albeit not for electron transfer but rather for direct interaction with the substrate. Together, these results demonstrate that phytoglobins are superior at hydroxylamine reduction because they have distal histidine coordination affinity constants near 1, and facile rate constants for binding and dissociation of the histidine side chain. Hexacoordinate hemoglobins such as neuroglobin are limited by tighter histidine coordination that blocks hydroxylamine binding, and pentacoordinate hemoglobins have intrinsically lower hydroxylamine affinities. PMID- 27661978 TI - Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region. AB - BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making. PMID- 27661979 TI - High-Performance Hybrid Electronic Devices from Layered PtSe2 Films Grown at Low Temperature. AB - Layered two-dimensional (2D) materials display great potential for a range of applications, particularly in electronics. We report the large-scale synthesis of thin films of platinum diselenide (PtSe2), a thus far scarcely investigated transition metal dichalcogenide. Importantly, the synthesis by thermally assisted conversion is performed at 400 degrees C, representing a breakthrough for the direct integration of this material with silicon (Si) technology. Besides the thorough characterization of this 2D material, we demonstrate its promise for applications in high-performance gas sensing with extremely short response and recovery times observed due to the 2D nature of the films. Furthermore, we realized vertically stacked heterostructures of PtSe2 on Si which act as both photodiodes and photovoltaic cells. Thus, this study establishes PtSe2 as a potential candidate for next-generation sensors and (opto-)electronic devices, using fabrication protocols compatible with established Si technologies. PMID- 27661980 TI - The D519G Polymorphism of Glyceronephosphate O-Acyltransferase Is a Risk Factor for Familial Porphyria Cutanea Tarda. AB - : Both familial and sporadic porphyria cutanea tarda (PCT) are iron dependent diseases. Symptoms of PCT resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y, c.843G>A, rs1800562) that enhances iron aborption by reducing hepcidin expression is a risk factor for PCT. Recently, a polymorphic variant (D519G, c.1556A>G, rs11558492) of glyceronephosphate O acyltransferase (GNPAT) was shown to be enriched in male patients with type I hereditary hemochromatosis (HFE C282Y homozygotes) who presented with a high iron phenotype, suggesting that GNPAT D519G, like HFE C282Y, is a modifier of iron homeostasis that favors iron absorption. To challenge this hypothesis, we investigated the frequency of GNPAT D519G in patients with both familial and sporadic PCT. Patients were screened for GNPAT D519G and allelic variants of HFE (both C282Y and H63D). Nucleotide sequencing of uroporphyrinogen decarboxylase (URO-D) identified mutant alleles. Patients with low erythrocyte URO-D activity or a damaging URO-D variant were classified as familial PCT (fPCT) and those with wild-type URO-D were classified as sporadic PCT (sPCT). GNPAT D519G was significantly enriched in the fPCT patient population (p = 0.0014) but not in the sPCT population (p = 0.4477). Both HFE C282Y and H63D (c.187C>G, rs1799945) were enriched in both PCT patient populations (p<0.0001) but showed no greater association with fPCT than with sPCT. CONCLUSION: GNPAT D519G is a risk factor for fPCT, but not for sPCT. PMID- 27661981 TI - Development and Validation of a Diabetic Retinopathy Referral Algorithm Based on Single-Field Fundus Photography. AB - PURPOSE: To develop a simplified algorithm to identify and refer diabetic retinopathy (DR) from single-field retinal images specifically for sight threatening diabetic retinopathy for appropriate care (ii) to determine the agreement and diagnostic accuracy of the algorithm as a pilot study among optometrists versus "gold standard" (retinal specialist grading). METHODS: The severity of DR was scored based on colour photo using a colour coded algorithm, which included the lesions of DR and number of quadrants involved. A total of 99 participants underwent training followed by evaluation. Data of the 99 participants were analyzed. Fifty posterior pole 45 degree retinal images with all stages of DR were presented. Kappa scores (kappa), areas under the receiver operating characteristic curves (AUCs), sensitivity and specificity were determined, with further comparison between working optometrists and optometry students. RESULTS: Mean age of the participants was 22 years (range: 19-43 years), 87% being women. Participants correctly identified 91.5% images that required immediate referral (kappa) = 0.696), 62.5% of images as requiring review after 6 months (kappa = 0.462), and 51.2% of those requiring review after 1 year (kappa = 0.532). The sensitivity and specificity of the optometrists were 91% and 78% for immediate referral, 62% and 84% for review after 6 months, and 51% and 95% for review after 1 year, respectively. The AUC was the highest (0.855) for immediate referral, second highest (0.824) for review after 1 year, and 0.727 for review after 6 months criteria. Optometry students performed better than the working optometrists for all grades of referral. CONCLUSIONS: The diabetic retinopathy algorithm assessed in this work is a simple and a fairly accurate method for appropriate referral based on single-field 45 degree posterior pole retinal images. PMID- 27661982 TI - Escape to Ferality: The Endoferal Origin of Weedy Rice from Crop Rice through De Domestication. AB - Domestication is the hallmark of evolution and civilization and harnesses biodiversity through selection for specific traits. In regions where domesticated lines are grown near wild relatives, congeneric sources of aggressive weedy genotypes cause major economic losses. Thus, the origins of weedy genotypes where no congeneric species occur raise questions regarding management effectiveness and evolutionary mechanisms responsible for weedy population success. Since eradication in the 1970s, California growers avoided weedy rice through continuous flood culture and zero-tolerance guidelines, preventing the import, presence, and movement of weedy seeds. In 2003, after decades of no reported presence in California, a weedy rice population was confirmed in dry-seeded fields. Our objectives were to identify the origins and establishment of this population and pinpoint possible phenotypes involved. We show that California weedy rice is derived from a different genetic source among a broad range of AA genome Oryzas and is most recently diverged from O. sativa temperate japonica cultivated in California. In contrast, other weedy rice ecotypes in North America (Southern US) originate from weedy genotypes from China near wild Oryza, and are derived through existing crop-wild relative crosses. Analyses of morphological data show that California weedy rice subgroups have phenotypes like medium-grain or gourmet cultivars, but have colored pericarp, seed shattering, and awns like wild relatives, suggesting that reversion to non-domestic or wild-like traits can occur following domestication, despite apparent fixation of domestication alleles. Additionally, these results indicate that preventive methods focused on incoming weed sources through contamination may miss burgeoning weedy genotypes that rapidly adapt, establish, and proliferate. Investigating the common and unique evolutionary mechanisms underlying global weed origins and subsequent interactions with crop relatives sheds light on how weeds evolve and addresses broader questions regarding the stability of selection during domestication and crop improvement. PMID- 27661983 TI - Predicting the Potential Distribution of Polygala tenuifolia Willd. under Climate Change in China. AB - Global warming has created opportunities and challenges for the survival and development of species. Determining how climate change may impact multiple ecosystem levels and lead to various species adaptations is necessary for both biodiversity conservation and sustainable biological resource utilization. In this study, we employed Maxent to predict changes in the habitat range and altitude of Polygala tenuifolia Willd. under current and future climate scenarios in China. Four representative concentration pathways (RCP2.6, RCP4.5, RCP6.0, and RCP8.5) were modeled for two time periods (2050 and 2070). The model inputs included 732 presence points and nine sets of environmental variables under the current conditions and the four RCPs in 2050 and 2070. The area under the receiver-operating characteristic (ROC) curve (AUC) was used to evaluate model performance. All of the AUCs were greater than 0.80, thereby placing these models in the "very good" category. Using a jackknife analysis, the precipitation in the warmest quarter, annual mean temperature, and altitude were found to be the top three variables that affect the range of P. tenuifolia. Additionally, we found that the predicted highly suitable habitat was in reasonable agreement with its actual distribution. Furthermore, the highly suitable habitat area was slowly reduced over time. PMID- 27661986 TI - Trabeculectomy Combined With Collagen Matrix Implant (Ologen). AB - PURPOSE OF THE STUDY: The purpose of the study was to report and evaluate outcomes of trabeculectomy with use of a subconjunctival biodegradable collagen matrix implant. PATIENTS AND METHODS: Retrospective review of trabeculectomy with Ologen implant of 65 eyes of 58 patients by the same surgeon from October, 2011 to October, 2014. Exclusion criteria were <6 months of follow-up after surgery, and uveitic or neovascular glaucoma. Demographic characteristics of the study population, visual acuity, intraocular pressure (IOP), glaucoma medications, bleb characteristics, and early and late postoperative complications were recorded. Complete and qualified IOP control success, <=15 and <=18 mm Hg, was calculated with the Kaplan-Meier analysis. RESULTS: The mean age of the patients in the study was 65.9+/-15.1 years. IOP was reduced from a mean of 21.4+/-9.2 to 12.3+/ 3.7 mm Hg at the last follow-up visit (P<0.0001). The number of IOP-lowering medications per eye was reduced from a mean of 1.86 preoperatively to 0.2 at the last follow-up visit (P<0.0001). The Kaplan-Meier survival curves of complete success for IOP<=15 mm Hg and <=18 mm Hg were 47.2% and 62.9%, respectively, at 36 months. Postoperative complications occurred in 15% of the eyes, with bleb leakage (6%) and hypotony (5%), which were resolved medically. At the last postoperative visit, blebs were described as normal (86.4%), flat (9.1%), and polycystic (4.5%). CONCLUSIONS: Trabeculectomy surgeries with Ologen performed by the same surgeon were effective in lowering IOP with a low complication rate at mid-term follow-up. PMID- 27661984 TI - High Serum Phosphorus Level Is Associated with Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis Patients. AB - OBJECTIVES: We initiated this study to explore the relationships of serum phosphorus level with left ventricular ultrasound features and diastolic function in peritoneal dialysis (PD) patients. METHODS: 174 patients with end-stage renal disease (ESRD) receiving PD were enrolled in this retrospective observational study. Conventional echocardiography examination and tissue Doppler imaging (TDI) were performed in each patient. Clinical information and laboratory data were also collected. Analyses of echocardiographic features were performed according to phosphorus quartiles groups. And multivariate regression models were used to determine the association between serum phosphorus and Left ventricular diastolic dysfunction (LVDD). RESULTS: With the increase of serum phosphorus levels, patients on PD showed an increased tissue Doppler-derived E/e' ratio of lateral wall (P < 0.001), indicating a deterioration of left ventricular diastolic function. Steady growths of left atrium and left ventricular diameters as well as increase of left ventricular muscle mass were also observed across the increasing quartiles of phosphorus, while left ventricular ejection fraction remained normal. In a multivariate analysis, the regression coefficient for E/e' ratio in the highest phosphorus quartile was almost threefold higher relative to those in the lowest quartile group. And compared with patients in the lowest phosphorus quartile (<1.34 mmol/L) those in the highest phosphorus quartile (>1.95 mmol/L) had a more than fivefold increased odds of E/e' ratio >15. CONCLUSIONS: Our study showed an early impairment of left ventricular diastolic function in peritoneal dialysis patients. High serum phosphorus level was independently associated with greater risk of LVDD in these patients. Whether serum phosphorus will be a useful target for prevention or improvement of LVDD remains to be proved by further studies. PMID- 27661987 TI - Congenital Glaucoma and CHARGE Syndrome: A Case Report. AB - PURPOSE: To report a rare case of congenital glaucoma in a patient with CHARGE syndrome, present gonioscopic photographs, and explore mechanisms of disease that may account for this association. PATIENTS AND METHODS: We describe a 35-week-old girl with previously diagnosed CHARGE syndrome who presented with corneal edema, buphthalmos, and elevated intraocular pressure in the left eye. She was subsequently diagnosed with congenital glaucoma and started on topical and oral therapy. RESULTS: Examination under anesthesia confirmed the above findings as well as bilateral abnormal angles with an anterior iris insertion at the level of the posterior trabecular meshwork, prominent iris vasculature and stromal strands, and nonvisible scleral spur and ciliary body bands. Trabeculotomy and trabeculectomy were performed in the left eye with a poor outcome. CHARGE syndrome is a complex neurocristopathy, and we propose that the abnormal angle findings and associated asymmetric glaucoma in our patient share a common mechanism of neural crest cell dysfunction. CONCLUSIONS: CHARGE syndrome can be associated with congenital glaucoma and we emphasize the importance of a thorough ophthalmic examination to detect glaucoma with surgical management as deemed appropriate. PMID- 27661988 TI - The Effect of Laser Photocoagulation on Intraocular Pressure in Premature Infants With Retinopathy of Prematurity. AB - PURPOSE: To evaluate the effects of diode laser treatment on intraocular pressure (IOP) of premature infants with retinopathy of prematurity (ROP). PATIENTS AND METHODS: The premature infants who underwent retinal laser photocoagulation therapy for ROP, and gestational age-matched, birth weight-matched, and sex matched premature infants with ROP which recovered spontaneously without any treatment were enrolled into the study. Anterior segment examination and longitudinal IOP and central corneal thickness measurements were performed 5 times as follows: 1 day before the laser treatment (T0), and 24 hours (T1), 1 week (T2), 1 month (T3), and 3 months (T4) after the laser treatment. Premature infants who experienced any complication related to the laser treatment were excluded from the study. RESULTS: Laser treated 67 premature infants and 70 premature infants in control group met inclusion criteria. Significant linear decreases in IOP and central corneal thickness values were measured throughout the study period for both groups (both, P<0.001). These changes were similar in 2 groups. There was a statistically insignificantly (P=0.999) and transient increase in the mean IOP value in the laser-treated group 24 hours after laser treatment. None of the patients in the laser-treated group experienced a shallow anterior chamber or a remarkable IOP elevation. CONCLUSIONS: Diode laser treatment for ROP was safe, and did not raise the IOP of premature infants. PMID- 27661990 TI - The Effect of Labor on the Intraocular Pressure in Healthy Women. AB - PURPOSE: To investigate the effect of modern vaginal labor using epidural anesthesia on the intraocular pressure (IOP) and on the mean ocular perfusion pressure (MOPP) in healthy women. PATIENTS AND METHODS: In this prospective observational study, eligible candidates were healthy pregnant women for vaginal delivery with epidural anesthesia, with a singleton pregnancy, who were admitted to the delivery room in the first phase of the first stage of labor. Demographic data as well as medical and obstetric history were obtained at baseline, followed by performance of a biomicroscopic examination. IOP, maternal heart rate, systolic blood pressure, and diastolic blood pressure were measured in the first, second and third stages of labor, 24+/-2 and 48+/-2 hours postpartum. IOP was not measured during the contraction phase of stage 2. MOPP was expressed as the difference between the arterial blood pressure and the IOP. Measurements were performed throughout the different stages of labor and were compared with baseline values. RESULTS: Thirty healthy white women were enrolled. Four women dropped out due to unexpected cesarean sections. The average age was 31.8+/-4.7 years. Nineteen participants received oxytocin during delivery. Twenty-three women were placed in a supine position, whereas 3 in a left decubitus position. No statistically significant changes were recorded in IOP (P=0.50) or MOPP (P=0.17) throughout the different stages of vaginal labor in this study. CONCLUSIONS: Vaginal delivery under epidural anesthesia is unlikely to cause significant damage to the optic nerve in healthy women. PMID- 27661989 TI - MRI Study of the Posterior Visual Pathways in Primary Open Angle Glaucoma. AB - PURPOSE OF THE STUDY: The purpose of the study was to evaluate neurodegeneration along brain visual pathways in primary open angle glaucoma (POAG) using improved analysis methods of volumetric and diffusion tensor magnetic resonance imaging (MRI) data. METHODS: Eleven POAG patients (60.0+/-9.2 y) with primarily mild to moderate POAG and 11 age-matched controls (55.9+/-7.5 y) were studied using structural and diffusion tensor MRI. Surface-based segmentation was applied to structural MRI to obtain visual cortical area and volume. Fiber tracking was applied to diffusion tensor data to obtain diffusion parameters along the optic tract and optic radiation. MRI parameters in glaucoma patients were compared with the corresponding left and right visual fields and retinal nerve fiber layer thicknesses, instead of with the left and right eye. RESULTS: Area and volume of the primary visual cortex were significantly reduced in POAG patients compared with controls (P<0.05) but did not correlate with visual field loss. Fractional anisotropy was reduced at multiple locations along the optic tracts and optic radiations in POAG patients compared with controls. Axial and radial diffusivity along the fiber tracts showed trends but were not significantly different between POAG patients and controls when averaged over the whole structures. Only fractional anisotropy (P<0.05) of the optic radiations was significantly correlated with visual field loss. No MRI parameters were correlated with retinal nerve fiber layer thickness. CONCLUSIONS: Improved analysis techniques of MRI data improves delineation of degeneration in the brain visual pathways and further supports the notion that neurodegeneration is involved with glaucoma pathogenesis. PMID- 27661991 TI - Refractive Outcome of Cataract Surgery in Eyes With Prior Trabeculectomy: Risk Factors for Postoperative Myopia. AB - PURPOSE: To examine refractive outcomes after phacoemulsification in eyes with prior trabeculectomy. DESIGN: Retrospective observational case-control study METHODS:: Comparison of eyes of glaucoma patients undergoing cataract surgery after trabeculectomy (study group) with a matched group with medically controlled glaucoma (control group). Laser interferometry was used to obtain ocular biometry. We measured the difference between the expected and actual postoperative refraction using third-generation and fourth-generation intraocular lens (IOL) prediction formulae (Haigis, Holladay 2, Hoffer Q, and SRK-T). A residual difference of >1.0 D of hyperopia or myopia was considered a "refractive surprise." RESULTS: In total, 86 eyes (85 patients) were included, including 23 eyes (22 patients) in the study group and 63 eyes (63 patients) in the control group. The mean follow-up was 12.2+/-4.1 months. Eyes (n=13) with trabeculectomy and a preoperative intraocular pressure (IOP)<=9 mm Hg had significantly more large myopic surprises than the control group for all IOL formulae (P=0.015 Haigis, P=0.003 Holladay 2, P=0.004 Hoffer Q, P=0.003 SRK-T). Eyes (n=10) with trabeculectomy and preoperative IOP>9 mm Hg, however, did not have significantly more myopic errors than the control (P>0.05, all formulae). An "IOP spike" defined as a >50% rise in IOP from baseline within 1 month of cataract surgery in the subgroup with preoperative IOP<=9 mm Hg (n=8) was associated with increased risk of large myopic surprise (3/8 subset vs. 1/63 control eyes for all formulae; P=0.004 Haigis, P=0.004 Holladay 2, P=0.001 Hoffer Q, P=0.004 SRK-T) as well as for large myopic and hyperopic surprises overall (4/8 subset vs. <=2/63 depending upon formulae; all P<=0.001). CONCLUSIONS: Low posttrabeculectomy IOP (<=9 mm Hg) is a risk factor for significant myopic surprise when undergoing subsequent cataract surgery despite using laser interferometry to measure ocular biometry and later generation formulae to determine IOL power. In addition, an IOP spike was associated with a 50% risk for large refractive surprise in this low IOP group. PMID- 27661992 TI - Measuring Intraocular Pressure in Patients With Keratoconus With and Without Intrastromal Corneal Ring Segments. AB - PURPOSE: To compare intraocular pressure (IOP) measurements made using 5 tonometers in keratoconic eyes with and without intrastromal corneal ring segments. METHODS AND PATIENTS: This was an observational case series study. A total of 147 eyes of 147 patients with keratoconus, 74 of which had undergone corneal ring segment placement, were prospectively evaluated. IOP was measured using the tonometers Tonopen XL, Pascal dynamic contour tonometer, iCare Pro, ocular response analyzer (ORA), and Goldmann applanation (GAT) in random order. The Bland-Altman method was used to examine interinstrument agreement. Effects on readings of central corneal thickness, corneal curvature, and corneal astigmatism were assessed by multivariate regression analysis. RESULTS: Smallest mean IOP differences with GAT measurements in eyes without and with ring segments, respectively, were detected for iCare Pro [0.2 (2.9) mm Hg and 0.4 (3.0) mm Hg, P=0.914] and greatest differences for ORA Goldmann-correlated IOP [5.8 (3.3) mm Hg and 6.0 (3.1) mm Hg, P=0.363]. Best agreement with GAT was shown by iCare Pro (ICC=0.829; 95% CI, 0.721-0.896) and worse agreement by ORA corneal-compensated IOP (ICC=-0.145; 95% CI, -0.826 to 0.283). All but the dynamic contour tonometer readings were influenced by central corneal thickness, yet these measurements were affected by the presence of ring segments (P=0.017) and corneal astigmatism (P=0.030). Corneal curvature only affected ORA Goldmann-correlated IOP (P=0.029). CONCLUSIONS: All 5 tonometers provided reliable IOP readings in the keratoconic eyes regardless of the presence of corneal ring segments. iCare Pro readings were most consistent with GAT, whereas ORA readings were least consistent with this reference standard. PMID- 27661994 TI - Optic Disc Swelling After Intraocular Pressure Lowering Treatment in Acute Primary Angle Closure. AB - PURPOSE OF THE STUDY: The purpose of the study was to report cases with acute primary angle closure where optic disc swelling was documented after intraocular pressure (IOP) lowering by laser iridotomy. PATIENTS AND METHODS: Two patients with acute primary angle closure underwent funduscopic examination of the optic disc and spectral-domain optical coherence tomography circumpapillary scanning at the time of acute primary angle closure attack before laser iridotomy, and after the laser iridotomy treatment. RESULTS: Optic disc swelling was developed in both patients following IOP lowering by laser iridotomy, which was documented by spectral-domain optical coherence tomography imaging as a diffuse thickening of the circumpapillary retinal nerve fiber layer. CONCLUSIONS: This is the first report demonstrating a temporal relationship between IOP lowering and optic disc swelling in patients with acute primary angle closure. Optic disc swelling documented after acute episode of acute primary angle closure may suggest choroidal effusion or axoplasmic overflow associated with sudden IOP lowering, rather than coexistence of other optic neuropathy. PMID- 27661993 TI - Efficacy of the Additional Use of Ripasudil, a Rho-Kinase Inhibitor, in Patients With Glaucoma Inadequately Controlled Under Maximum Medical Therapy. AB - PURPOSE OF THE STUDY: The purpose of the study was to evaluate the intraocular pressure (IOP)-lowering effect and tolerability of ripasudil, a rho-kinase inhibitor, in patients with glaucoma inadequately controlled with maximum medical therapy. PATIENTS AND METHODS: This prospective, noncomparative, interventional case series study included 35 patients with primary open angle glaucoma, in whom the glaucoma was poorly controlled with maximum medical therapy before starting the treatment with ripasudil. Ripasudil was instilled twice a day as adjunctive therapy to the ongoing glaucoma treatment. The primary end point was the degree of IOP reduction after 3 months of treatment, whereas the secondary end points were the percentage of patients reaching the predefined target IOP and the incidence of adverse events. RESULTS: We examined 35 eyes of 35 patients with primary open angle glaucoma. The IOP reduction (relative percentage IOP reduction) from baseline was -2.8 mm Hg (-15.5%; 95% confidence interval, -1.6 to -3.9 mm Hg; P<0.001) after 3 months of treatment. The predefined target IOP was achieved in 48.5% (17/35) of the patients. The adverse events were conjunctival hyperemia (all patients), allergic conjunctivitis (2 patients), and ophthalmalgia (1 patient). CONCLUSIONS: The addition of ripasudil was effective in lowering the IOP in patients with glaucoma poorly controlled with maximal medical therapy; moreover, the drug was well tolerated. In 48.5% of the patients in whom the predefined target IOP was achieved, this adjunctive therapy helped avoid glaucoma surgery at least in the short term. PMID- 27661995 TI - XEN-augmented Baerveldt: A New Surgical Technique for Refractory Glaucoma. AB - BACKGROUND: Glaucoma drainage devices have traditionally been reserved for patients with refractory glaucoma. However, these devices are prone to various sight-threatening complications. To prevent hypotony after placement of the Baerveldt tube, surgeons traditionally tie the tube with an absorbable suture until encapsulation occurs around the plate. We hypothesized that combining the XEN tube, placing it in the anterior chamber and connecting it to the Baerveldt tube posteriorly, outside the anterior chamber, would minimize 2 main potentially blinding complications: hypotony and corneal disease. PURPOSE: To describe a new surgical technique for refractory glaucoma, combining both the Baerveldt and the XEN tubes in the same surgery. SURGICAL TECHNIQUE: The Baerveldt implant was positioned in the superotemporal quadrant and sutured to the sclera. A scleral flap was executed extending from the anterior margin of the plate for the entire length of the tube to the limbus. The Baerveldt tube was correctly positioned by removing a deeper scleral flap. The XEN tube was then inserted ab externo and inserted into the Baerveldt tube's lumen. The newly formed double tube was then sutured and covered by the first scleral flap and usual suturing of the conjunctiva was performed. CONCLUSIONS: This technique is simple and potentially increases the safety of refractory glaucoma surgeries. PMID- 27661996 TI - Image-Based Single Cell Profiling: High-Throughput Processing of Mother Machine Experiments. AB - BACKGROUND: Microfluidic lab-on-chip technology combined with live-cell imaging has enabled the observation of single cells in their spatio-temporal context. The mother machine (MM) cultivation system is particularly attractive for the long term investigation of rod-shaped bacteria since it facilitates continuous cultivation and observation of individual cells over many generations in a highly parallelized manner. To date, the lack of fully automated image analysis software limits the practical applicability of the MM as a phenotypic screening tool. RESULTS: We present an image analysis pipeline for the automated processing of MM time lapse image stacks. The pipeline supports all analysis steps, i.e., image registration, orientation correction, channel/cell detection, cell tracking, and result visualization. Tailored algorithms account for the specialized MM layout to enable a robust automated analysis. Image data generated in a two-day growth study (~ 90 GB) is analyzed in ~ 30 min with negligible differences in growth rate between automated and manual evaluation quality. The proposed methods are implemented in the software molyso (MOther machine AnaLYsis SOftware) that provides a new profiling tool to analyze unbiasedly hitherto inaccessible large scale MM image stacks. CONCLUSION: Presented is the software molyso, a ready-to use open source software (BSD-licensed) for the unsupervised analysis of MM time lapse image stacks. molyso source code and user manual are available at https://github.com/modsim/molyso. PMID- 27661999 TI - Furthering the Validity of a Tool to Assess Simulated Pregnancy Options Counseling Skills. AB - OBJECTIVE: To further the validity of a tool to assess nondirective pregnancy options counseling skills. METHODS: Using a cross-sectional design, we explored four sources of construct validity evidence for an objective structured clinical examination for training and assessment of nondirective pregnancy options counseling: content, response process, internal structure, and relations to other variables. Content of the previously developed tool was enhanced through input from five family medicine educators. The objective structured clinical examination was implemented in a family medicine clerkship with third-year medical students from 2014 to 2015 using trained raters. Response process was addressed after a pilot round. Three new raters evaluated videotapes of 46 performances. Cronbach's alpha, intraclass correlation coefficients, and Spearman's rho were estimated with 95% confidence intervals. RESULTS: The content validity was affirmed. Cronbach's alpha was 0.71. According to Landis and Koch's criteria, all but two items unique to the clinical situation of pregnancy options counseling generated substantial to perfect agreement (0.62-1.00). Relations to other variables within the checklist were strong, ranging from 0.66 to 0.87. DISCUSSION: This tool for assessing pregnancy options counseling skills has excellent content and strong internal structure. Further work to improve the Global Rating Scale may be necessary for summative use. PMID- 27661998 TI - Expert perspectives on hereditary angioedema: Key areas for advancements in care across the patient journey. AB - BACKGROUND: Published literature documents the substantial burden of hereditary angioedema (HAE) with C1 inhibitor deficiency on the quality of life and work productivity of patients. However, despite advances in the field and the availability of guidelines to advise health care providers (HCP) on the diagnosis and management of HAE, there are still many challenges to overcome. For example, delayed diagnosis and misdiagnosis are common, and treatment practices vary worldwide. OBJECTIVE: An international expert panel was convened to consider opportunities for improvements that would benefit patients with HAE. METHODS: Based on professional and personal experiences, the experts developed schematics to describe the journey of patients through the following stages: (1) onset of symptoms and initial evaluation; (2) referral/diagnosis; and (3) management of HAE. More importantly, the panel identified key areas in which it was possible to optimize the support provided to patients and HCPs along this journey. RESULTS: Overall, this approach highlighted the need for wider dissemination of algorithms and scientific data to more effectively educate HCPs from multiple disciplines and the need for more research to inform appropriate treatment decisions. Furthermore, HAE awareness campaigns, accurate online information, and referral to patient advocacy groups were all considered helpful approaches to support patients. CONCLUSION: More detailed and widespread information on the diagnosis and management of HAE is needed and may lead to advancements in care throughout the journey of the patient with HAE. PMID- 27661997 TI - Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study. AB - The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed. PMID- 27662000 TI - Advising and Interview Patterns of Medical Students Pursuing Obstetrics and Gynecology Residency. AB - OBJECTIVE: To describe the advising practices at medical schools and interview patterns among medical students pursuing obstetrics and gynecology residency training. METHODS: A voluntary, anonymous survey was distributed to all applicants interviewing for obstetrics and gynecology residency during the 2014 2015 cycle at the University of Colorado, University of Washington, University of California, San Francisco, and Loyola University. Demographic data were obtained. The survey explored student advising in the residency application process including number of applications and interviews recommended by advisors. Data are reported as percentage for each survey item and compared by select demographics using an exact chi. RESULTS: Among 315 unique possible applicants, 73% (n=230) responded. Students were most commonly advised by the obstetrics and gynecology clerkship director (33%) with recommendations to apply to 21-30 programs (48%). Thirty-four percent of students applied to 21-30 programs, 32% to 31-40 programs, and 30% to greater than 40 programs. Students were advised (70%) and planned (55%) to interview at 10-14 programs. Concern over competitiveness of the applicant pool was the most important factor (31%) in determining the number of applications. The number of programs advised to or plan to interview at was greater for those in the couples match (P<.001). CONCLUSION: Medical students pursuing obstetrics and gynecology are most likely to be advised by obstetrics and gynecology clerkship directors and concern over the competitiveness of the applicant pool results in students applying to large numbers of programs. This practice may adversely affect the obstetrics and gynecology match process for both programs and applicants through the requirements of managing additional applications and potentially needing to complete a greater number of interviews. PMID- 27662001 TI - The Labor Games. AB - OBJECTIVE: To develop and evaluate a simulation laboratory designed to stimulate learning and increase medical students' preparedness for an obstetrics and gynecology clinical clerkship. METHODS: Ninety-seven medical students participated in the games during their obstetrics and gynecology clerkship in 1 year. Using the resident-as-teacher model, students rotated through seven stations, each with a simulated obstetric task. Points were awarded at each station, and the student with the highest score won. Self-perceived proficiency level and general preparedness for the clerkship were evaluated through paired pregame and postgame assessments. RESULTS: Postassessment results showed statistically significant (P<.001) increases in self-perceived competence performing all tested skills including reading fetal heart tracings, knot-tying, measuring cervical dilation, amniotomy, estimating fetal weight, and estimating blood loss. Approximately 97% enjoyed The Labor Games, 97.9% reported increased knowledge, and 96.9% learned valuable skills. Students also reported feeling more prepared for the obstetrics and gynecology rotation (2.6 compared with 3.3, P<.001). DISCUSSION: The Labor Games improved medical students' self-confidence and self-perceived skill level on obstetric tasks. Students also felt more prepared for the obstetrics and gynecology clerkship. This study creates a low cost and reproducible simulation laboratory that is identified as effective by medical students in teaching skills, knowledge, and preparedness for an obstetrics and gynecology clerkship. PMID- 27662002 TI - Electronic Learning-Spaced Education to Facilitate Resident Knowledge and Guide Program Didactics. AB - OBJECTIVE: To evaluate the use of mobile technology to facilitate resident learning, assess clinical knowledge, and guide curricular development in a busy clinical environment. METHODS: This was a cross-sectional study conducted in a large (N=48) urban obstetrics and gynecology residency program. Question sets were created in the following areas: office gynecology, general obstetrics, gynecologic surgery and urogynecology, maternal-fetal medicine and ultrasonography, reproductive endocrinology and pediatric gynecology, and gynecologic oncology. Using an educational mobile application (app), questions were sent monthly to resident smartphones with immediate feedback on answer accuracy along with answer explanation and references. Outcomes included app use, which was determined by how quickly participants answered questions (very active active indicates questions answered within 7 days) and proficiency (mean percentage correct) calculated for individuals, resident class level, and by content area. RESULTS: All 48 residents participated and 77.4% were very active or active app users. On average, participants answered correctly 61.0% on the first attempt and improved to 78.3% on repeat attempt (P<.001). Proficiency was lowest for gynecologic surgery and highest for general obstetrics. CONCLUSION: A mobile app to support e-learning was successfully implemented in our program; its use was associated with knowledge retention and identification of low-proficiency topics to guide curriculum development. PMID- 27662003 TI - Narrative Medicine Workshops for Obstetrics and Gynecology Residents and Association With Burnout Measures. AB - OBJECTIVE: To determine whether a workshop Narrative Medicine curriculum can improve burnout among obstetrics and gynecology residents. METHODS: A Narrative Medicine curriculum was conducted at three obstetrics and gynecology training programs. An explanatory research design examined correlation between Narrative Medicine attendance and changes in survey responses. Residents completed a pretest and 1-year posttest survey that included validated measures of burnout and empathy. A within-participants design used baseline pretest scores as an internal control and measured changes in individual scores. The primary outcome of the study was change in burnout rates. Mann-Whitney U and Kruskal-Wallis tests were used to analyze the data. RESULTS: A total of 66 residents at three institutions participated in the Narrative Medicine curriculum. Of those, 54 (81%) enrolled in the study by completing any part of the surveys, and 43 (80%) of those enrolled had complete data for analysis. Burnout was high on all Maslach Burnout Inventory subscales and increased over 1 year. Participants with high Narrative Medicine attendance had decreased burnout on the Emotional Exhaustion subscale (-4.1 [+/-8.1]) points compared with an increase of 0.5 (+/-6.0) for low attendance participants (U=134, P=.02, d=0.65). Lower self-care ratings were associated with improved Personal Accomplishment (+0.5 [+/-5.0]) compared with +2.0 (+/-2.7), U=84, P=.01]. Other characteristics did not significantly correlate with burnout or empathy. CONCLUSION: Burnout was high and worsened over time among obstetrics and gynecology residents in these three programs. Higher attendance at Narrative Medicine workshops was associated with improved Emotional Exhaustion. PMID- 27662004 TI - Simulation to Improve Trainee Knowledge and Comfort About Twin Vaginal Birth. AB - OBJECTIVE: To describe a simulation-based curriculum on twin vaginal delivery and evaluate its effects on trainee knowledge and comfort about twin vaginal birth. METHODS: Trainees participated in a three-part simulation consisting of a patient counseling session, a twin delivery scenario, and a breech extraction skills station. Consenting trainees completed a 21-item presimulation survey and a 22 item postsimulation survey assessing knowledge, experience, attitudes, and comfort surrounding twin vaginal birth. Presimulation and postsimulation results were compared using univariate analysis. Our primary outcomes were change in knowledge and comfort before and after the simulation. RESULTS: Twenty-four obstetrics and gynecology residents consented to participation with 18 postsimulation surveys available for comparison (75%). Trainees estimated their participation in 445 twin deliveries (median 19, range 0-52) with only 20.4% of these as vaginal births. Participants reported a need for more didactic or simulated training on this topic (64% and 88%, respectively). Knowledge about twin delivery improved after the simulation (33.3% compared with 58.3% questions correct, P<.01). Before training, 33.3% of participants reported they would strongly counsel a patient to attempt vaginal birth instead of elective cesarean delivery for twins compared with 50% after training (P=.52). Personal comfort with performing a breech extraction of a nonvertex second twin improved from 5.5% to 66.7% after the simulation (P<.01). CONCLUSION: Resident exposure to twin vaginal birth is infrequent and variable with a demonstrable need for more training. Our contemporary obstetric climate is prioritizing vaginal birth despite less frequent operative obstetric interventions. We describe a reproducible twin delivery simulation associated with a favorable effect on resident knowledge and comfort levels. PMID- 27662006 TI - Foreword and Onward. PMID- 27662005 TI - Comfort With Skills and Knowledge After Immediate Postpartum Intrauterine Device Training. AB - OBJECTIVE: To estimate whether a standardized immediate postpartum intrauterine device (IUD) simulation results in sustained improvement in perceived comfort with procedural skills. METHODS: From November 2013 to April 2015, obstetric health care providers at two teaching hospitals participated in a 30-minute immediate postpartum IUD simulation workshop and program evaluation. We assessed knowledge of indications, insertion technique, safety, and comfort with knowledge and skills preintervention immediately after and 6 months posttraining. RESULTS: Training participants (N=84) included 39 residents and 45 attendings (25 certified nurse-midwives and 20 obstetrician-gynecologists). Fifty-seven participants (68%) completed the 6-month assessments. Many participants had placed immediate postpartum IUDs before the training (54% of residents compared with 64% of attendings, P=.32); 60% were comfortable with their knowledge and 52% with their insertion skills defined by self-assessment of 7 or greater on a 10 point scale. On the pretest, 77% answered 80% or greater of the knowledge-based questions correctly; this proportion rose to 95% and 97% on the immediate and 6 month assessments, respectively, and were similar between residents and attendings. Immediately posttraining, 94% of participants rated their comfort with knowledge at 7 or greater out of 10; this fell to 86% by 6 months. Likewise, 87% and 74% scored their comfort with skills at 7 or greater out of 10 immediately and at 6 months, respectively. By 6 months, 81% reported placing one or more immediate postpartum IUDs(92% of residents and 71% of attendings, P=.05). CONCLUSION: Residents and attendings demonstrate sustained improvement in knowledge and comfort with immediate postpartum IUDs 6 months after a standardized simulation workshop. PMID- 27662007 TI - miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1). AB - BACKGROUND Polycystic ovarian syndrome (PCOS) is a common metabolic disorder in premenopausal woman, characterized by hyperandrogenism, oligoanovulation, and insulin resistance. microRNAs play pivotal roles in regulating key factors of PCOS. However, relevant research remains limited. This study aimed to reveal the role and potential mechanism of miR-483 in PCOS. MATERIAL AND METHODS PCOS patients (n=20) were recruited for detecting miR-483 expression in lesion and normal ovary cortex. Human granulosa-like tumor cell line KGN was used to alter miR-483 expression by cell transfection. Cell viability and proliferation were analyzed by MTT assay and colony formation assay, and cell cycle was detected by flow cytometry. Interaction between miR-483 and IGF1 was verified by luciferase reporter assay. KGN cells were further treated by insulin to investigate the relationship between miR-483 and insulin. RESULTS miR-483 was significantly down regulated in lesion ovary cortex from PCOS patients (P<0.001). In KGN cells, overexpression of miR-483 inhibited cell viability and proliferation, and induced cell cycle arrest. miR-483 also inhibited CCNB1, CCND1, and CDK2. miR-483 sponge induced the opposite effects. miR-483 directly targeted IGF1 3'UTR, and IGF1 promoted KGN cell proliferation and reversed miR-483-inhibited cell viability. Insulin treatment in KGN cells inhibited miR-483, and promoted IGF1 and cell proliferation. CONCLUSIONS These results suggest that miR-483 is a PCOS suppressor inhibiting cell proliferation, possibly via targeting IGF1, and that it is involved in insulin-induced cell proliferation. miR-483 is a potential alternative for diagnosing and treating PCOS. PMID- 27662008 TI - Characterization of Ammonia, Methane, and Nitrous Oxide Emissions from Concentrated Animal Feeding Operations in Northeastern Colorado. AB - Atmospheric emissions from animal husbandry are important to both air quality and climate, but are hard to characterize and quantify as they differ significantly due to management practices and livestock type, and they can vary substantially throughout diurnal and seasonal cycles. Using a new mobile laboratory, ammonia (NH3), methane (CH4), nitrous oxide (N2O), and other trace gas emissions were measured from four concentrated animal feeding operations (CAFOs) in northeastern Colorado. Two dairies, a beef cattle feedlot, and a sheep feedlot were chosen for repeated diurnal and seasonal measurements. A consistent diurnal pattern in the NH3 to CH4 enhancement ratio is clearly observed, with midday enhancement ratios approximately four times greater than nighttime values. This diurnal pattern is similar, with slight variations in magnitude, at the four CAFOs and across seasons. The average NH3 to CH4 enhancement ratio from all seasons and CAFOs studied is 0.17 (+0.13/-0.08) mol/mol, in agreement with statewide inventory averages and previous literature. Enhancement ratios for NH3 to N2O and N2O to CH4 are also reported. The enhancement ratios can be used as a source signature to distinguish feedlot emissions from other NH3 and CH4 sources, such as fertilizer application and fossil fuel development, and the large diurnal variability is important for refining inventories, models, and emission estimates. PMID- 27662009 TI - Innate lymphoid cells are expanded and functionally altered in chronic lymphocytic leukemia. PMID- 27662010 TI - The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes. AB - We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3 level biomarker risk group based on these values separated risks of transplant related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival. PMID- 27662011 TI - Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation. AB - Myelofibrosis is a myeloproliferative neoplasm that results in cytopenia, bone marrow fibrosis and extramedullary hematopoiesis. Allogeneic hematopoietic stem cell transplantation is the only curative treatment but is associated with a risk of delayed engraftment and graft failure. In this study, patients with myelofibrosis (n=31) and acute myeloid leukemia (n=31) were analyzed for time to engraftment, graft failure and engraftment-related factors. Early and late neutrophil engraftment and late thrombocyte engraftment were significantly delayed in patients with myelofibrosis as compared to acute myeloid leukemia, and graft failure only occurred in myelofibrosis (6%). Only spleen size had a significant influence on engraftment efficiency in myelofibrosis patients. To analyze the cause for the engraftment defect, clearance of hematopoietic stem cells from peripheral blood was measured and immunohistological staining of bone marrow sections was performed. Numbers of circulating CD34+ were significantly reduced at early time points in myelofibrosis patients, whereas CD34+CD38- and colony-forming cells showed no significant difference in clearance. Staining of bone marrow sections for homing proteins revealed a loss of VCAM-1 in myelofibrosis with a corresponding significant increase in the level of soluble VCAM-1 within the peripheral blood. In conclusion, our data suggest that reduced engraftment and graft failure in myelofibrosis patients is caused by an early pooling of CD34+ hematopoietic stem cells in the spleen and a bone marrow homing defect caused by the loss of VCAM-1. Improved engraftment in myelofibrosis might be achieved by approaches that reduce spleen size and cleavage of VCAM-1 in these patients prior to hematopoietic stem cell transplantation. PMID- 27662013 TI - Increased risk of axial fractures in patients with untreated chronic lymphocytic leukemia: a population-based analysis. PMID- 27662012 TI - Mutating heme oxygenase-1 into a peroxidase causes a defect in bilirubin synthesis associated with microcytic anemia and severe hyperinflammation. PMID- 27662015 TI - Interleukin-6 receptor-alpha signaling drives anti-RBC alloantibody production and T-follicular helper cell differentiation in a murine model of red blood cell alloimmunization. PMID- 27662014 TI - Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura. AB - Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (P<0.0001). The plasma levels of HNP1-3 correlated with the levels of plasma complement fragment Bb (rho=0.48, P=0.0004) and serum lactate dehydrogenase (rho=0.28, P=0.04); in addition, the plasma levels of Bb correlated with iC3b (rho=0.55, P<0.0001), sC5b-9 (rho=0.63, P<0.0001), serum creatinine (rho=0.42, p=0.0011), and lactate dehydrogenase (rho=0.40, P=0.0034), respectively. Moreover, the plasma levels of iC3b and sC5b-9 were correlated (rho=0.72, P<0.0001), despite no statistically significant difference of the two markers between thrombotic thrombocytopenic purpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients. PMID- 27662016 TI - A prospective randomized trial comparing cyclosporine/methotrexate and tacrolimus/sirolimus as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation. AB - Improvement of graft-versus-host disease prophylaxis remains an important goal in allogeneic hematopoietic stem cell transplantation. Based on reports of possibly preferential properties of sirolimus, we compared the standard regimen of cyclosporine and methotrexate (n=106) with a combination of tacrolimus and sirolimus (n=103) as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation in a prospective, open, randomized trial. The hypothesis was that the tacrolimus/sirolimus regimen would lead to less acute graft-versus-host disease and reduced transplant-related mortality. There was no significant difference in the cumulative incidence of acute graft-versus-host disease of grades II-IV (41% vs. 51%; P=0.19) or grades III-IV (13% vs. 7%; P=0.09) between the groups. Time to neutrophil engraftment (18 days vs. 17 days; P=0.24) was similar, but time to platelet engraftment was longer in cyclosporine/methotrexate patients (14 vs. 12 days; P<0.01). No significant differences in incidence of oropharyngeal mucositis, time to full donor chimerism, or number of cytomegalovirus infections were seen between the two treatment arms, and transplant-related toxicities were equally distributed. Triglyceride (P=0.005) and cholesterol (P=0.009) levels were higher in tacrolimus/sirolimus patients. Transplant-related mortality (18% vs. 12%; P=0.40) and 5-year overall survival (72% vs. 71%; P=0.71) were similar. Five-year relapse free survival in patients with malignant diagnoses was 65% in the cyclosporine/methotrexate group and 63% in the tacrolimus/sirolimus group (P=0.73). We conclude that tacrolimus/sirolimus remains a valid and safe alternative to cyclosporine/methotrexate as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation, with comparable transplant-related outcomes. The trial was registered at clinicaltrials.gov identifier: 00993343. PMID- 27662017 TI - Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. AB - Graft-versus-host disease-free relapse-free survival, which is defined as the absence of grade III-IV acute graft-versus-host disease, systemically treated chronic graft-versus-host disease, relapse, and death, is a novel, meaningful composite end point for clinical trials. To characterize risk factors and differences in graft-versus-host disease-free relapse-free survival according to a variety of graft sources, we analyzed 23,302 patients with hematologic malignancy that had a first allogeneic transplantation from 2000 through 2013 using the Japanese national transplant registry database. The 1-year graft-versus host disease-free relapse-free survival rate was 41% in all patients. The rate was higher after bone marrow transplantation than after peripheral blood stem cell transplantation due to the lower risks of III-IV acute and chronic graft versus-host disease. The rate was highest after HLA-matched sibling bone marrow transplantation. The rate after single cord blood transplantation was comparable to that after HLA-matched unrelated bone marrow transplantation among patients aged 20 years or under, and was comparable or better than other alternative graft sources among patients aged 21 years or over, due to the low risk of chronic graft-versus-host disease. Other factors associated with better graft-versus-host disease-free relapse-free survival include female patients, antithymocyte globulin prophylaxis (for standard-risk disease), recent years of transplantation, sex combinations other than from a female donor to a male patient, the absence of prior autologous transplantation, myeloablative conditioning, negative cytomegalovirus serostatus, and tacrolimus-based prophylaxis. These results provide important information to guide the choice of graft sources and are benchmarks for future graft-versus-host disease prophylaxis studies. PMID- 27662020 TI - One-pot reductive-acetylation of nitroarenes with NaBH4 catalyzed by separable core-shell Fe3O4@Cu(OH)x nanoparticles. AB - One-pot reductive-acetylation of nitroarenes to acetanilides was carried out efficiently with NaBH4 in the presence of magnetically separable core-shell Fe3O4@Cu(OH)x nanoparticles. All reactions were carried out in H2O followed by acetylation with acetic anhydride within 5-17min giving the N-arylacetamides in high to excellent yields. Reusability of the catalyst was examined 9 times without significant loss of its catalytic activity. PMID- 27662019 TI - Hypertension and the eye. AB - PURPOSE OF REVIEW: Hypertension is the primary risk factor for cardiovascular disease and mortality that consists a major public health issue worldwide. Hypertension triggers a series of pathophysiological ocular modifications affecting significantly the retinal, choroidal, and optic nerve circulations that result in a range of ocular effects.The retina is the only place in the body where microvasculature can be directly inspected, providing valuable information on hypertension related systemic risks.The aim of this review is to provide an update on latest advances regarding the detection and significance of hypertension related eye signs. RECENT FINDINGS: It's been shown that measurable retinal microvascular changes may precede progression of systemic microvascular disease.Last years, there are emerging advances in the field retinal imaging and computer software analysis that have enabled the objective and accurate assessment of retinal vascular caliber, while in association with latest epidemiological studies several other retinal vascular features have been recognized, such as vascular length-to-diameter ratio, and wall-to-lumen ratio that may also be associated to hypertension.Additionally, recent genetic studies have provided some insight to vascular pathophysiological processes having correlated new chromosome's loci to hypertensive retinopathy signs. SUMMARY: Assessment of hypertensive retinopathy signs may convey additional prognostic information on the risk of end-organ damage and may alert for urgent systemic management or even preventive systemic therapies. Further development of retinal vascular imaging and computerized system may provide a significant tool to improve the diagnosis, prognosis, and management of hypertension in clinical practice. PMID- 27662021 TI - Novel hierarchical tantalum oxide-PDMS hybrid coating for medical implants: One pot synthesis, characterization and modulation of fibroblast proliferation. AB - Surface properties such as morphology, roughness and charge density have a strong influence on the interaction of biomaterials and cells. Hierarchical materials with a combination of micron/submicron and nanoscale features for coating of medical implants could therefore have significant potential to modulate cellular responses and eventually improve the performance of the implants. In this study, we report a simple, one pot wet chemistry preparation of a hybrid coating system with hierarchical surface structures consisting of polydimethylsiloxane (PDMS) and tantalum oxide. Medical grade, amine functional PDMS was mixed with tantalum ethoxide which subsequently formed Ta2O5in situ through hydrolysis and condensation during coating process. The coatings were characterized by SEM, EDS, XPS, confocal scanning microscopy, contact angle measurement and in vitro cell culture. Varying PDMS and tantalum ethoxide ratios resulted in coatings of different surface textures ranging from smooth to submicro- and nano-structured. Strikingly, hierarchical surfaces containing both microscale (1-1.5MUm) and nanoscale (86-163nm) particles were found on coatings synthesized with 20% and 40% (v/v) tantalum ethoxide. The coatings were similar in term of hydrophobicity but showed different surface roughness and chemical composition. Importantly, higher cell proliferation was observed on hybrid surface with hierarchical structures compared to pure PDMS or pure tantalum oxide. The coating process is simple, versatile, carried out under ambient condition and requires no special equipment. PMID- 27662022 TI - Controlled synthesis of BiVO4/SrTiO3 composite with enhanced sunlight-driven photofunctions for sulfamethoxazole removal. AB - The presence of antibiotics in surface waters is paid more and more attention, which is difficult to be removed by conventional treatment technology, and photocatalytic technology is considered to be a promising method for antibiotics pollutant removal. In the present work, a novel heterojunction photocatalyst was successfully synthesized by self-template method under hydrothermal condition. The photocatalytic activity of as-prepared samples was investigated by degradation of sulfamethoxazole in aqueous solution. The BiVO4/SrTiO3 composites showed superior photocatalytic efficiency under xenon lamp irradiation. The recycling tests proved that BiVO4/SrTiO3 composite was high stability and easily separated. The degradation efficiency of BiVO4/SrTiO3 composite was also greatly influenced by active species. It indicated that approximately 50% TOC reduction was achieved after 1h photocatalytic reaction. The intermediates were investigated by LC-MS analyses, which revealed that the bonds of CO, CS, CC, CN, isoxazole ring and benzene ring were broken by attacking of active species. PMID- 27662023 TI - Development of electrochemical sensor for the determination of palladium ions (Pd2+) using flexible screen printed un-modified carbon electrode. AB - To date, the development of different modified electrodes have received much attention in electrochemistry. The modified electrodes have some drawbacks such as high cost, difficult to handle and not eco friendly. Hence, we report an electrochemical sensor for the determination of palladium ions (Pd2+) using an un modified screen printed carbon electrode has been developed for the first time, which are characterized and studied via scanning electron microscope and cyclic voltammetry. Prior to determination of Pd2+ ions, the operational conditions of un-modified SPCE was optimized using cyclic voltammetry and showed excellent electro-analytical behavior towards the determination of Pd2+ ions. Electrochemical determination of Pd2+ ions reveal that the un-modified electrode showed lower detection limit of 1.32MUM with a linear ranging from 3 to 133.35MUM towards the Pd2+ ions concentration via differential pulse voltammetry. The developed sensor also applied to the successfully determination of trace level Pd2+ ions in spiked water samples. In addition, the advantage of this type of electrode is simple, disposable and cost effective in electrochemical sensors. PMID- 27662018 TI - Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial. AB - Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741). PMID- 27662024 TI - Molybdenum disulfide nanosheets coated multiwalled carbon nanotubes composite for highly sensitive determination of chloramphenicol in food samples milk, honey and powdered milk. AB - We have described a hybrid material that consists of molybdenum disulfide nanosheets (MoS2) coated on functionalized multiwalled carbon nanotubes (f MWCNTs) for sensitive and selective determination of chloramphenicol (CAP). The MoS2/f-MWCNTs nanocomposite was successfully prepared through a hydrothermal process and its structure was characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, electrochemical impedance spectroscopy and cyclic voltammetry. The MoS2/f-MWCNTs nanocomposite holds excellent electrochemical properties and it displays excellent electrocatalytic ability to CAP. Under optimized working conditions, the nanocomposite film modified electrode responds linearly to CAP in the concentration range of 0.08-1392MUM. The detection limit was obtained as 0.015MUM (+/-0.003). The electrode has high level of selectivity in presence of large excess concentrations of interfering species. In addition, the modified electrode offers satisfactory repeatability, reproducibility and stability. The practical applicability of the electrode was demonstrated in food samples such as, milk, powdered milk and honey samples and the recoveries are agreeable which clearly revealed its practical feasibility in food analysis. PMID- 27662025 TI - Soft- to network hard-material for constructing both ion- and electron-conductive hierarchical porous structure to significantly boost energy density of a supercapacitor. AB - Soft-material PEDOT is used to network hard Co3O4 nanowires for constructing both ion- and electron-conductive hierarchical porous structure Co3O4/PEDOT to greatly boost the capacitor energy density than sum of that of plain Co3O4 nanowires and PEDOT film. Specifically, the networked hierarchical porous structure of Co3O4/PEDOT is synthesized and tailored through hydrothermal method and post electrochemical polymerization method for the PEDOT coating onto Co3O4 nanowires. Typically, Co3O4/PEDOT supercapacitor gets a highest areal capacitance of 160mFcm 2 at a current density of 0.2mAcm-2, which is about 2.2 times larger than the sum of that of plain Co3O4 NWs (0.92mFcm-2) and PEDOT film (69.88mFcm-2). Besides, if only PEDOT as active mass is counted, Co3O4/PEDOT cell can achieve a highest capacitance of 567.21Fg-1, this is the highest capacitance value obtained by PEDOT-based supercapacitors. Furthermore, this soft-hard network porous structure also achieves a high cycling stability of 93% capacitance retention after the 20,000th cycle. This work demonstrates a new approach to constructing both ion and electron conductive hierarchical porous structure to significantly boost energy density of a supercapacitor. PMID- 27662026 TI - A new route to the shape-controlled synthesis of nano-sized gamma-alumina and Ag/gamma-alumina for selective catalytic reduction of NO in the presence of propene. AB - We report a new route for the direct synthesis of gamma-alumina nanocrystals with size and shape control in the presence of oleylamine as the capping agent. Their morphology can be controlled from nanospheres to nanorods by simply tuning a proper amount of concentrated nitric acid (67%) in the synthetic mixture. The as made nanoparticle products after calcination show gamma-alumina nano-size with unique porosity and high specific surface area and retained morphology. The XRD patterns of these calcined samples exhibit broad diffraction lines which are characteristic of nanocrystal size of gamma-alumina. This synthesis procedure has been extended to the one-pot synthesis of nano-alumina based Ag catalysts with spherical and rod-shaped nano-alumina morphologies. Selective catalytic reduction (SCR) of NO with C3H6 over these catalysts was investigated. The results were compared to those of the conventional Ag/gamma-Al2O3 and gamma-nanoalumina alone. These nano-alumina based Ag catalysts exhibit excellent NO reduction activity in the presence of C3H6. Even in the presence of large oxygen concentration (15%), N2 yields as high as ~90% at quite low temperature (~350 degrees C) have been achieved. The significantly high catalytic activity of this new type of nanocatalysts can also be attributed to their high surface area and good dispersion of silver species in the alumina matrix as well as the synergism and new properties that arise at the silver-nanoalumina interface. PMID- 27662027 TI - Solvent-resistant CTAB-modified polymethylsilsesquioxane aerogels for organic solvent and oil adsorption. AB - In this work, we describe the successful synthesis of super-hydrophobic polymethylsilsesquioxane (PMSQ) aerogels with a porous network by a sol-gel polymerization process using methyltrimethoxysilane (MTMS) reactants with the addition of cetyltrimethylammonium bromide (CTAB) surfactants. The specific surface area, pore size and hydrophobicity of the CTAB-modified PMSQ aerogels were investigated for different amounts of CTAB doping. The specific surface areas of the pristine and CTAB-modified PMSQ aerogels with C/M molar ratios of 0.001, 0.002 and 0.004 were 491, 301, 342 and 298m2/g, respectively. The water contact angles of the CTAB-modified PMSQ aerogels with C/M molar ratios of 0.001, 0.002 and 0.004 were 166.38 degrees , 165.62 degrees and 166.43 degrees , confirming the super-hydrophobicity of the CTAB-modified PMSQ aerogels. Compared to pristine PMSQ aerogels, the as-prepared CTAB-modified PMSQ aerogels exhibit more solvent-resistant properties in ethanol (EtOH) and n-hexane solvents. The as prepared CTAB-modified PMSQ aerogels were further used for organic solvent and oil adsorption applications. Consequently, the as-prepared CTAB-modified PMSQ aerogels have great potential for organic solvent and oil adsorption in industrial applications. PMID- 27662028 TI - A combined self-assembly and calcination method for preparation of nanoparticles assembled cobalt oxide nanosheets using graphene oxide as template and their application for non-enzymatic glucose biosensing. AB - Cobalt oxide (Co3O4)-based materials have been extensively investigated as efficient electrocatalysts for non-enzymatic glucose biosensing. The proper tuning the structure of Co3O4-based materials could improve sensing performances for glucose detection. Herein, we have developed a combined self-assembly and calcination method to prepare nanoparticles-assembled Co3O4 nanosheets, which exhibit good sensing performances for glucose biosensing. The Co3O4 nanosheets were prepared by the following three steps: (i) the Co2+ modified graphene oxide (GO) was prepared by the self-assembly of Co2+ and GO in aqueous solution firstly, and then Co2+ modified GO film was obtained by vacuum filtration method; (ii) after calcination of Co2+ modified GO film in N2 atmosphere, Co3O4 nanoparticles modified reduced GO (RGO) was obtained; (iii) finally, nanoparticles-assembled Co3O4 nanosheets were obtained by calcination of Co3O4 modified RGO in air to remove RGO template. Most importantly, Co3O4 nanosheets exhibit good electrocatalytic activity for oxidation of glucose, leading to high performance glucose sensor. The detection limit and linear range of Co3O4 nanosheets-based glucose sensor in the present work are 0.15MUM, and 1-50MUM, respectively. Furthermore, such sensor also shows excellent selectivity for glucose detection, compared to the commonly interfering species including dopamine, and uric acid. PMID- 27662030 TI - Non-exchanging hydroxyl groups on the surface of cellulose fibrils: The role of interaction with water. AB - The interaction of water with cellulose stages many unresolved questions. Here 2H MAS NMR and IR spectra recorded under carefully selected conditions in 1H-2H exchanged, and re-exchanged, cellulose samples are presented. It is shown here, by a quantitative and robust approach, that only two of the three available hydroxyl groups on the surface of cellulose fibrils are exchanging their hydrogen with the surrounding water molecules. This finding is additionally verified and explained by MD simulations which demonstrate that the 1HO(2) and 1HO(6) hydroxyl groups of the constituting glucose units act as hydrogen-bond donors to water, while the 1HO(3) groups behave exclusively as hydrogen-bond acceptors from water and donate hydrogen to their intra-chain neighbors O(5). We conclude that such a behavior makes the latter hydroxyl group unreactive to hydrogen exchange with water. PMID- 27662029 TI - One-pot synthesis of nitrogen and sulfur co-doped carbon dots and its application for sensor and multicolor cellular imaging. AB - Nitrogen and sulfur co-doped carbon dots (N, S/C-dots) were prepared via one-pot hydrothermal treatment of citric acid and cystamine dihydrochloride. The as prepared N, S/C-dots exhibited excellent excitation-wavelength-independent photoluminescence property and higher fluorescence quantum yield (QY) of 39.7% compared to C,N-dots (QY=2.6%) prepared using citric acid and 1,6-diaminohexane dihydrochloride as the precursor. The N, S/C-dots were well-dispersed in aqueous solution and showed good photoluminescence stabilities in different pH and temperature without any surface modification. Additionally, the fluorescence of N, S/C-dots can be quenched based on inner filter effect (IFE) upon the addition of Cr(VI) and showed good selectivity and sensitivity to Cr(VI). The detection for Cr(VI) exhibited a good linear correlation ranging from 1 to 80MUM with a detection limit of 0.86MUM. What's more, in comparison with other quantum dots and organic dyes, these N, S/C-dots were much more eco-friendly and can be used for multicolor bioimaging. PMID- 27662031 TI - Structure-activity relationship (SAR) study and design strategies of nitrogen containing heterocyclic moieties for their anticancer activities. AB - The present review article offers a detailed account of the design strategies employed for the synthesis of nitrogen-containing anticancer agents. The results of different studies describe the N-heterocyclic ring system is a core structure in many synthetic compounds exhibiting a broad range of biological activities. Benzimidazole, benzothiazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, triazoles, quinolines and quinazolines including others drugs containing pyridazine, pyridine and pyrimidines are covered. The following studies of these compounds suggested that these compounds showed their antitumor activities through multiple mechanisms including inhibiting protein kinase (CDK, MK-2, PLK1, kinesin-like protein Eg5 and IKK), topoisomerase I and II, microtubule inhibition, and many others. Our concise representation exploits the design and anticancer potency of these compounds. The direct comparison of anticancer activities with the standard enables a systematic analysis of the structure-activity relationship among the series. PMID- 27662032 TI - Design, synthesis and evaluation of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives as potent inhibitors of platelet aggregation. AB - Based upon LX2421, a previously identified antiplatelet aggregation agent, a series of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives were designed, synthesized and evaluated. Among them, compounds LX14 and LX25 were identified as promising antiplatelet aggregation agents. The in vitro biologic study demonstrated that LX14 can block platelet aggregation induced by four different inducers and displays comparable potency in inhibiting GPIIb/IIIa receptor in comparison with Tirofiban. In addition, LX14 has much lower risk of bleeding than Tirofiban and shows significant antithrombotic activity in vivo. Taking together, the results indicated that LX14 is a promising GPIIb/IIIa receptor antagonist against platelet aggregation worthy of further evaluation. PMID- 27662033 TI - Cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: Synthetic studies and in vitro gene transfer. AB - In this communication we describe the construction of four succinic-based cationic lipids, their formulation with plasmid DNA (pDNA), and an evaluation of their in vitro gene delivery into Chinese hamster ovarian (CHO-K1) cells. The cationic lipids employed in this work possess either a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. The synthesized lipids and a co-lipid of neutral charge, either cholesterol or 1,2 dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were formulated in an overall 3:2 cationic-to-neutral lipid molar ratio, then complexed with plasmid DNA (pDNA). The relative transfection performance was evaluated via a comparison between matched versus mismatched formulations defined by the rigidity relationship between the lipids employed. Gel electrophoresis was used to characterize the binding of the lipid formulations with plasmid DNA and the relative degree of plasmid degradation using a DNase I degradation assay. Small angle X-ray diffraction (SAXD) was employed to characterize the packing morphology of the lipid-DNA complexes. In general, the succinic unit embedded within the hydrophobic domain of the cationic lipids was found to improve lipid hydration. The transfection assays revealed a general trend in which mismatched formulations that employed a rigid lipid combined with a non-rigid (or flexible) lipid, outperformed the matched formulations. The results from this work suggest that the design of the cationic lipid structure and the composition of the lipoplex formulation play key roles in governing the transfection performance of nonviral gene delivery agents. PMID- 27662034 TI - The replacement of the 2-methoxy substituent of N-((6,6-diphenyl-1,4-dioxan-2 yl)methyl)-2-(2-methoxyphenoxy)ethan-1-amine improves the selectivity for 5-HT1A receptor over alpha1-adrenoceptor and D2-like receptor subtypes. AB - N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-amine (3) is a potent 5-HT1A receptor and alpha1d-adrenoceptor (alpha1d-AR) ligand. Analogues 5-10 were rationally designed and prepared to evaluate whether electronic and/or lipophilic properties of substituents in the ortho position of its phenoxy moiety exert any favorable effects on the affinity/activity at 5-HT1A receptor and improve selectivity over alpha1-ARs. To rationalize the experimental observations and derive information about receptor-ligand interactions of the reported ligands, docking studies, using 5-HT1A and alpha1d-AR models generated by homology techniques, and a retrospective computational study were performed. The results highlighted that proper substituents in position 2 of the phenoxy moiety of 3 selectively address the ligands toward 5-HT1A receptor with respect to alpha1-ARs and D2-like receptor subtypes. Methoxymethylenoxy derivative 9 showed the best 5-HT1A selectivity profile and the highest potency at 5-HT1A receptor, behaving as a partial agonist. Finally, 9, tested in light/dark exploration test in mice, significantly reduced anxiety-linked behaviors. Therefore, it may be considered a lead for the design of partial agonists potentially useful in the treatment of disorders in which 5-HT1A receptor is involved. PMID- 27662035 TI - Frequent NFIB-associated Gene Rearrangement in Adenoid Cystic Carcinoma of the Vulva. AB - Adenoid cystic carcinoma is a rare malignant tumor that usually arises in the major and minor salivary glands and other locations containing secretory glands, including the lower female genital tract. Lower female genital tract carcinomas with adenoid cystic differentiation can be subclassified into 2 distinct groups based on the presence or absence of high-risk HPV. Cervical mixed carcinomas with some adenoid cystic differentiation are high-risk HPV-related but pure adenoid cystic carcinomas of vulvar and cervical origin appear to be unrelated to high risk HPV. Mechanisms by which normal cells give rise to an HPV-unrelated adenoid cystic carcinoma remain largely unknown. Studies demonstrate that chromosomal translocation involving the genes encoding the transcription factors MYB and NFIB functions as a driving force of adenoid cystic carcinomas development regardless of anatomic site. The current study used fluorescence in situ hybridization with 3 different probes including MYB break-apart probe, NFIB break-apart probe, and MYB-NFIB fusion probe to assess for the presence of gene rearrangements in adenoid cystic carcinomas of the vulva. Six (66.7%) of 9 vulvar adenoid cystic carcinomas demonstrated NFIB rearrangement. Of these 6 cases with a disturbed NFIB, only 2 cases (33.3%) were positive for a MYB rearrangement that was also confirmed by a positive MYB-NFIB fusion pattern. NFIB-associated gene rearrangement is a frequent genetic event in vulvar adenoid cystic carcinomas. Chromosome translocations involving NFIB but with an intact MYB indicate the presence of novel oncogenic mechanisms for the development of adenoid cystic carcinomas of the vulva. PMID- 27662036 TI - Primary Mucinous Carcinoma of the Fallopian Tube: Case Report and Review of Literature. AB - Primary mucinous carcinoma of the fallopian tube is extremely rare. We report the detailed characterization of a mucinous carcinoma arising in the fimbrial end of the fallopian tube in a 74-yr-old woman. The patient presented with recurrent urinary tract infection and urinary tract obstruction secondary to a large right ovarian mass. She had an appendicectomy as an 11 yr old. Serum CA-125 was raised at 239 U/mL. Computed tomographic scans showed bilateral, cystic ovarian tumors but no other intra-abdominal abnormality. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omental biopsy. Microscopy showed mucinous carcinoma arising from the left tubal fimbriae, in association with mucinous metaplasia over the uninvolved fimbrial folds. There was no mucinous metaplasia in the contralateral fallopian tube, endometrial lining, cervix, or on the uterine serosal surface. A mucinous borderline tumor of gastrointestinal subtype was identified in the left ovary. The right ovary contained a benign mucinous cystadenoma of mixed gastrointestinal and endocervical-like/Mullerian subtype. The fallopian tube tumor expressed CK7, claudin 18, and MUC6, but not CK20, CDX2, CEA, pyloric gland mucin (recognized by HIK1083), ER, or vimentin. The immunolabelling pattern for p53 was wild-type, and p16 expression was nonblock. The metaplastic mucinous tubal epithelium also marked for CK7, CK20, CDX2, and CEA but had mutation-type p53 labelling (p53 null), a low Ki-67 index, and was immunopositive for HIK1083, MUC6, and claudin 18. This is the first detailed characterization of a primary mucinous fallopian tube carcinoma and the adjacent metaplastic mucinous epithelium, and confirms it to be of gastric type. PMID- 27662037 TI - XXIX. Dr Hazel Mansell Gore. PMID- 27662038 TI - The association between parental attributions of misbehavior and parenting practices in caregivers raising children with prenatal alcohol exposure: A mixed methods study. AB - BACKGROUND AND AIMS: Limited research has focused on parenting practices used by caregivers raising children with fetal alcohol spectrum disorders (FASD). The current study hypothesized that parental attributions of children's misbehavior would relate to the parenting strategies caregivers utilize with children with FASD. This study also aimed to develop a coding scheme to allow quantification of these treatment-relevant constructs in future intervention trials. METHODS: Thirty-one caregivers of children with FASD (age 4-8) were interviewed with the Parenting Practices Interview (PPI), a study-developed qualitative interview. Quantitative measures of FASD knowledge, parenting sense of competence and stress, and child behavior problems were included. Mixed-method analyses assessed the relationship between parental attributions of misbehavior and parenting practices. RESULTS: Caregivers who attributed their child's misbehavior to underlying neurodevelopmental disabilities were more likely to use antecedent strategies and feel more confident in managing their child's behavior. Parents who attributed their child's misbehavior to willful disobedience were more likely to rely on consequence strategies and feel more ineffective. CONCLUSIONS: Results are consistent with theoretical models for FASD parent training interventions. Assessment of theorized mechanisms of change in intervention trials is needed; the development of the PPI and quantitative coding system will facilitate this type of research. PMID- 27662039 TI - ATG proteins: Are we always looking at autophagy? AB - Autophagy is an intracellular degradation pathway that is regulated by the autophagy-related (ATG) proteins. For a long time it has been thought that ATG proteins were exclusively required for autophagy, but recent experimental evidence has revealed that these proteins are part of other cellular pathways, individually or as a functional group. To estimate the extent of these so-called unconventional functions of the ATG proteins, we decided to perform an unbiased siRNA screen targeting the entire ATG proteome and used viral replication as the readout. Our results have uncovered that a surprisingly high number of ATG proteins (36%) have a positive or negative role in promoting virus replication outside their classical role in autophagy. With the increasing knowledge about ATG protein unconventional functions and our investigation results, the interpretations about the possible involvement of autophagy in cellular or organismal functions that solely rely on the depletion of a single ATG protein, should be considered cautiously. PMID- 27662040 TI - Type 1 diabetes, quality of life, occupational status and education level - A comparative population-based study. AB - AIM: Type 1 diabetes requires extensive self-management to avoid complications and may have negative effects on the everyday life of people with the disease. The aim of this study was to compare adults with type 1 diabetes to the general population in terms of health-related quality of life, occupational status (level of employment, working hours and sick leave) and education level. METHODS: 2415 adults (aged 18-98years) with type 1 diabetes were compared to 48,511 adults (aged 18-103years) from the general population. Data were obtained from two cross sectional surveys conducted in 2010 and 2011 of adults living or treated in the Capital Region in Denmark. Differences between adults with type 1 diabetes and the general population were standardised for age and sex and analyzed using linear probability models and negative binomial regression. Differences were further analyzed in subgroups. RESULTS: Compared to the general population, adults with type 1 diabetes experienced lower health-related quality of life, were more frequently unemployed, had more sick leave per year and were slightly better educated. Differences in health-related quality of life and employment increased with age and were larger among women, as compared to men. No significant differences were found with regard to working hours. CONCLUSION: Our findings suggest that type 1 diabetes is associated with lower health-related quality of life, higher unemployment and additional sick leave. The negative association with type 1 diabetes is more pronounced in women and older adults. PMID- 27662041 TI - Comparison of cardiovascular and metabolic outcomes in people with type 2 diabetes on insulin versus non-insulin glucose-lowering therapies (GLTs): A systematic review and meta-analysis of clinical trials. AB - OBJECTIVES: To compare the cardiovascular and metabolic outcomes of Insulin versus non-insulin glucose lowering therapy (GLT). METHODS: We included randomised control trials (RCTs) which randomised patients aged >18years with Type 2 Diabetes (T2D) to insulin vs non-insulin GLT. We used risk ratios (RR), risk difference (RD) and odds ratios (OR) with 95% confidence interval (95%CI) to analyse the treatment effects of dichotomous outcomes and mean differences (with 95% CI) for continuous outcomes. RESULTS: We included 18 RCTs with 19,300 participants. There was no significant difference in the risk of all-cause mortality and CV events between the groups (RR=1.01; 95%CI: 0.96-1.06; p=0.69). In 16 trials, insulin showed greater efficacy in glycaemic control (mean diff= 0.20; 95%CI: -0.28 to -0.11) but the proportion achieving HbA1c level of either ?7.0% or 7.4% (53 or 57mmol/mol) was similar in both (OR=1.55; 95%CI=0.92-2.62). The non-insulin group had a significant reduction in weight (mean diff=-3.41; 95%CI: -4.50 to -2.32) and an increase in the proportion of adverse events (54.7% vs 45.3%, p=0.044), but the insulin group showed an (RR=1.90; 95%CI: 1.44-2.51) increased risk of hypoglycaemia. CONCLUSION: There was no difference in the risk of all-cause mortality and adverse cardiovascular (CV) events between Insulin and non-insulin GLTs. Insulin was associated with superior reduction in HbA1c; least reduction in weight and higher risk of hypoglycaemia. Both showed similar proportion of patients achieving HbA1c target. Non-insulin GLTs were associated with a higher risk in reported adverse drug events. PMID- 27662042 TI - A comparison of the pharmacodynamic profiles of jet-injected regular human insulin versus conventionally administered insulin aspart in healthy volunteers. AB - AIMS: Rapid-acting insulin analogues are generally preferred over regular human insulin because of their more immediate onset of action and shorter time-action profile. However, these analogues may not always be tolerated by or universally available for people with insulin-requiring diabetes. Jet injection has been demonstrated to facilitate faster insulin absorption. We determined whether administration of regular human insulin by jet injection achieves the same pharmacological properties as that of a rapid-acting insulin analogue. METHODS: Twenty healthy volunteers received regular human insulin (0.2units/kg) by jet injection. Glucose 20% was infused intravenously to maintain euglycaemia over six hours. The glucose infusion rates (GIR) were determined to compare pharmacological profiles. These profiles were compared with data from two other studies in which a similar dose of insulin aspart was administered by conventional pen. RESULTS: Regular human insulin by jet injection had a faster onset of glucose-lowering effect compared to aspart by conventional pen (T GIR50%, 30.8+/-2.9 versus 43.1+/-3.2min, P<0.01). There were no differences in time to maximal GIR (106.1+/-11.9 versus 95.8+/-9.2min, P=0.50), maximal GIR (8.6+/-0.7 versus 7.7+/-0.7mg/kg/min, P=0.0.33), total glucose-lowering effect (101.0+/-9.8 versus 87.6+/-7.0g, P=0.28), and time until 50% of glucose disposal (144.8+/-5.6 versus 151.3+/-5.1min, P=0.39). CONCLUSIONS: Jet-injected regular human insulin had a pharmacological profile that was essentially not dissimilar from that of aspart insulin administered by conventional pen, and can therefore be used as an alternative for conventionally administered rapid-acting insulin analogues. PMID- 27662043 TI - The Talking Cure of Avoidant Personality Disorder: Remission through Earned Secure Attachment. AB - The concept of earned security is important and has significant implications for psychotherapy. Understanding how individuals with insecure attachment styles can develop secure attachment styles through reparative relationships, such as the therapeutic relationship, can assist psychotherapists in helping patients to overcome the effects of early negative life experiences. Personality disorders are commonly associated with negative experiences, such as abuse, neglect, and other empathic failures. These disorders are particularly difficult to treat because of their pervasive nature and the resultant defense mechanisms that often thwart psychotherapy. However, an understanding of the role that attachment can play in the etiology, symptomatology, and treatment of psychopathology can greatly enhance the therapeutic process. This case report describes the long-term psychodynamic psychotherapy of a woman with a history of childhood trauma, avoidant attachment style, and avoidant personality disorder. Through the therapeutic relationship, she developed a secure attachment, and her symptoms remitted, and her life drastically improved. PMID- 27662044 TI - A Four-Component Model of Sexual Orientation & Its Application to Psychotherapy. AB - Distress related to sexual orientation is a common focus in psychotherapy. In some instances the distress is external in nature as with persecution, and in others it is internal as with self-acceptance issues. Complicating matters, sexual orientation is a very complex topic producing a great deal of confusion for both clients and therapists. The current paper provides a four component model-sexual orientation dimensions, activation of these dimensions, the role of erotic fantasy, and social construction of sexual orientation-that in combination provide a comprehensive perspective. Activation of dimensions is a novel contribution not proposed in any other model. With improved understanding of sexual orientation issues, and utilization of this knowledge to guide interventions, psychotherapists can improve outcomes with their clients. Also described is how dimensions of sexual orientation relate to transgender. In addition to improving psychotherapy outcomes, the fourcomponent model presented can help reduce discrimination and persecution, by demonstrating that the capacity for both homoerotic and heteroerotic behavior is universal. PMID- 27662045 TI - The Cardiac Rhythm of the Unconscious in a Case of Panic Disorder. AB - The field of psychodynamic psychotherapy would benefit from a comprehensive model that integrates its constructs with neurobiology. Research on the autonomic nervous system activity during the psychotherapeutic process is necessary because it is key in affective experiences and defensive behavior. The current case study reports physiological findings on heart rate dynamics in a patient suffering from panic disorder during two therapeutic sessions in which we used Davanloo's Intensive Short-term Dynamic Psychotherapy. We looked at various metrics of heart rate variability during the therapeutic process leading to breakthrough of unconscious feelings. The measurements included sympathetic and parasympathetic indices, vagal tone, and their responses. Our results suggest that the sympathetic system activates during defensive responses associated with anxiety and during the passage of unconscious-aggressive impulses. Following the experience of unconscious guilt, there is an increased vagal tone corresponding to the phase of reunification with the attachment figure. Findings are discussed integrating developmental neurobiology and clinical psychodynamics. PMID- 27662046 TI - Can Frontline Clinicians in Public Psychiatry Settings Provide Effective Psychotherapy For Psychosis? AB - This report consists of the personal reflections of seven frontline clinicians who participated in a formal training program for the psychotherapy of psychosis implemented in a large public clinic setting. The training was part of a quality improvement initiative, consisting of 12 hours of didactic presentation followed by 30 hours of weekly peer-group supervision. The clinicians comment on ways of working with patients prior to the training, and how their views and techniques changed as a result of the training. The reflections of frontline staff provide proof of the concept that psychotherapy for psychosis techniques can be added to existing clinical skills, and that it is possible to implement a program in psychotherapy for psychosis in a busy public clinic. PMID- 27662047 TI - Practicing Psychoanalysis and Psychodynamic Psychotherapies in Developing Societies. AB - Vital to the contemporary exercise of psychiatry is the biopsychosocial approach, with psychotherapy as its well-defined, and requisite, constituent. The key objectives of psychoanalysis and other related therapies are the amelioration of symptoms and modification of character by probing the unconscious. But the practice of psychoanalysis and similar insight-oriented techniques is in developing nations is different from developed countries due to cultural and educational reasons, along with a shortage of required facilities. The result often is ignorance of exploratory techniques and the substitution of approaches, such cognitive and behavior therapies, which operate at the conscious and subconscious levels of mind. Additionally, decreased implementation of psychotherapy by psychiatrists in industrialized countries may discourage its use by therapists in developing societies. This article is devoted to developing, traditional, or conservative societies and the obstacles confronted in the progression of applied (clinical) psychoanalysis and related methods in the classroom and practice. Possible solutions also are discussed briefly. PMID- 27662048 TI - Treatment of high-strength sulfate wastewater using an autotrophic biocathode in view of elemental sulfur recovery. AB - Treatment of high-strength sulfate wastewaters is becoming a research issue not only for its optimal management but also for the possibility of recovering elemental sulfur. Moreover, sulfate-rich wastewater production is expected to grow due to the increased SO2 emission contained in flue gases which are treated by chemical absorption in water. Bioelectrochemical systems (BESs) are a promising alternative for sulfate reduction with a lack of electron donor, since hydrogen can be generated in situ from electricity. However, complete sulfate reduction leads to hydrogen sulfide as final sulfur compound. This work is the first to demonstrate that, in addition to an efficient sulfate-rich wastewater treatment, elemental sulfur could be recovered in a biocathode of a BES under oxygen limiting conditions. The key of the process is the biological oxidation of sulfide to elemental sulfur simultaneously to the sulfate reduction in the cathode using the oxygen produced in the anode that diffuses through the membrane. High sulfate reduction rates (up to 388 mg S-SO42- L-1 d-1) were observed linked to a low production of sulfide. Accumulation of elemental sulfur over graphite fibers of the biocathode was demonstrated by energy dispersive spectrometry, discarding the presence of metal sulfides. Microbial community analysis of the cathode biofilm demonstrated the presence of sulfate-reducing bacteria (mainly Desulfovibrio sp.) and sulfide-oxidizing bacteria (mainly Sulfuricurvum sp.). Hence, this biocathode allows simultaneous biological sulfate reduction and biological sulfide oxidation to elemental sulfur, opening up a novel process for recovering sulfur from sulfate-rich wastewaters. PMID- 27662049 TI - Dermatologic Surgery Needs in Low-Income, Uninsured, and Minority Communities. PMID- 27662050 TI - Picosecond 532 nm Neodymium-Doped Yttrium Aluminium Garnet Laser for the Treatment of Solar Lentigines in Darker Skin Types: Safety and Efficacy. PMID- 27662051 TI - Toluidine Blue and Hematoxylin and Eosin Stains are Comparable in Evaluating Squamous Cell Carcinoma During Mohs. AB - BACKGROUND: Histologic examination of tissue is the foundation of Mohs micrographic surgery because determination of surgical margins influences whether additional tissue will be taken. Currently, there is no large focused study comparing toluidine blue (TB) and hematoxylin and eosin (H&E) stains in the evaluation of squamous cell carcinoma (SCC). OBJECTIVE: This study evaluates whether TB and H&E are comparable in assessing the presence of tumor in frozen sections of SCC. MATERIALS AND METHODS: One hundred eighty-six randomized slides representing 93 tissue pieces from 36 tumors were examined by 3 Mohs surgeons (1 Accreditation Council for Graduate Medical Education fellow and 2 fellowship trained surgeons) and compared using a template that documented the presence and location of tumor on the slides. RESULTS: The evaluation of SCC with H&E and TB stains was highly concordant, with concordant identification of SCC in 96%, 96%, and 94% of tissue layers among the 3 Mohs surgeons ARS, LHG, and AK-A, respectively. CONCLUSION: Toluidine blue and H&E stains are statistically similar in their ability to detect SCC and guide Mohs surgical decision-making. PMID- 27662052 TI - Progressively Worsening Hypersensitivity Reaction to Bupivacaine. PMID- 27662053 TI - Reconstruction of a Large Divided Nevus of the Eyelid. PMID- 27662054 TI - Safety and Long-Term Efficacy of Forehead Contouring With a Polycaprolactone Based Dermal Filler. AB - BACKGROUND: Recently, a biostimulatory dermal filler based on polycaprolactone (PCL) microspheres was introduced. To our knowledge, no report has examined the safety and efficacy of PCL-based dermal fillers in forehead augmentation. OBJECTIVE: To evaluate the safety and efficacy of forehead augmentation using a PCL-based dermal filler. MATERIALS AND METHODS: The study population consisted of 58 patients (57 women, 98%; 1 man, 2%), aged 20 to 65 years, undergoing forehead augmentation using a PCL-based dermal filler between October 2013 and October 2015 at our clinic. The physicians used the Global Aesthetic Improvement Scale (GAIS) to evaluate its efficacy 1, 3, 6, 12, and 24 months postoperatively. RESULTS: The mean GAIS score at 1, 3, 6, 12, and 24 months was 2.14 +/- 0.95, 2.38 +/- 0.77, 2.50 +/- 0.76, 2.45 +/- 0.52, and 2.33 +/- 0.50, respectively. The scores increased markedly from 1 to 3 months and were maintained at 24 months. CONCLUSION: A PCL-based dermal filler is a good option for soft tissue augmentation of the forehead, as it is safe and has long-lasting favorable cosmetic efficacy. PMID- 27662055 TI - Visual motion processing subserving behavior in crabs. AB - Motion vision originated during the Cambrian explosion more than 500 million years ago, likely triggered by the race for earliest detection between preys and predators. To successfully evade a predator's attack a prey must react quickly and reliably, which imposes a common constrain to the implementation of escape responses among different species. Thus, neural circuits subserving fast escape responses are usually straightforward and contain giant neurons. This review summarizes knowledge about a small group of motion-sensitive giant neurons thought to be central in guiding the escape performance of crabs to visual stimuli. The flexibility of the escape behavior contrasts with the stiffness of the optomotor response, indicating a task-dependent early segregation of visual pathways. PMID- 27662057 TI - Comprehensive Review on the Use of Graphene-Based Substrates for Regenerative Medicine and Biomedical Devices. AB - Recent research suggests that graphene holds great potential in the biomedical field because of its extraordinary properties. Whereas initial attempts focused on the use of suspended graphene for drug delivery and bioimaging, more recent work has demonstrated its advantages for preparing substrates for tissue engineering and biomedical devices and products. Cells are known to interact with and respond to nanoparticles differently when presented in the form of a substrate than in the form of a suspension. In tissue engineering, a stable and supportive substrate or scaffold is needed to provide mechanical support, chemical stimuli, and biological signals to cells. This review compiles recent advances of the impact of both graphene and graphene-derived particles to prepare supporting substrates for tissue regeneration and devices as well as the associated cell response to multifunctional graphene substrates. We discuss the interaction of cells with pristine graphene, graphene oxide, functionalized graphene, and hybrid graphene particles in the form of coatings and composites. Such materials show excellent biological outcomes in vitro, in particular, for orthopedic and neural tissue engineering applications. Preliminary evaluation of these graphene-based materials in vivo reinforces their promise for tissue regeneration and implants. Although the reported findings of studies on graphene based substrates are promising, several questions and concerns associated with their in vivo use persist. Possible strategies to examine these issues are presented. PMID- 27662056 TI - Target detection in insects: optical, neural and behavioral optimizations. AB - Motion vision provides important cues for many tasks. Flying insects, for example, may pursue small, fast moving targets for mating or feeding purposes, even when these are detected against self-generated optic flow. Since insects are small, with size-constrained eyes and brains, they have evolved to optimize their optical, neural and behavioral target visualization solutions. Indeed, even if evolutionarily distant insects display different pursuit strategies, target neuron physiology is strikingly similar. Furthermore, the coarse spatial resolution of the insect compound eye might actually be beneficial when it comes to detection of moving targets. In conclusion, tiny insects show higher than expected performance in target visualization tasks. PMID- 27662058 TI - Total Synthesis of Miuraenamides A and D. AB - Miuraenamides A and D, cyclodepsipeptides with antimicrobial and antitumor activity, were synthesized. The synthesis of an unsaturated hydroxycarboxylic acid moiety, starting from a chiral epoxide, was achieved by Suzuki-Miyaura coupling as a key step. As a result, the overall yield for miuraenamide A over the longest linear sequence is 3.2%, while the yield of the previously reported procedure is 1.9%. In addition, the cell growth-inhibitory activity and anti Phytophthora activity of the synthesized compounds were evaluated. PMID- 27662059 TI - Archaic admixture in human history. AB - Modern humans evolved in Southern or Eastern Africa, and spread from there across the rest of the world. As they expanded across Africa and Eurasia, they encountered other hominin groups. The extent to which modern and 'archaic' human groups interbred is an area of active research, and while we know that modern humans interbred with Neanderthals and Denisovans, there is not yet agreement on how many admixture events there were or on how much Neanderthal or Denisovan DNA can be found in contemporary genomes. Here we review what is known about archaic admixture in human history, with a focus on what has been discovered in the past 2 years. PMID- 27662061 TI - An update in the endoscopic management of gastric cancer. AB - PURPOSE OF REVIEW: Gastric cancer remains a leading cause of mortality worldwide and gastroenterologists are playing an increasingly larger role in its management. This article reviews the endoscopic management of gastric cancer, with emphasis on recent advances in the field. RECENT FINDINGS: Long-term studies comparing surgery and endoscopic resection for early gastric cancer have shown no difference in 10-year survival rates. Second-look endoscopy, performed 2 days after endoscopic submucosal dissection (ESD) to address the concern of delayed bleeding, may not affect rebleeding rates. Magnesium, proton pump inhibitors, and bupivacaine may help reduce post-ESD pain. New devices such as the Clutch Cutter and EndoLifter may help make ESD easier and safer. SUMMARY: Endoscopic therapy for early gastric cancer is becoming increasingly popular and innovations are constantly being made to improve technique and technology. This review focuses on the latest approaches to the endoscopic management of gastric cancer. PMID- 27662062 TI - Periprocedural Management of Direct Oral Anticoagulants Should Be Guided by Accurate Laboratory Tests. PMID- 27662060 TI - Recent advances in the study of fine-scale population structure in humans. AB - Empowered by modern genotyping and large samples, population structure can be accurately described and quantified even when it only explains a fraction of a percent of total genetic variance. This is especially relevant and interesting for humans, where fine-scale population structure can both confound disease mapping studies and reveal the history of migration and divergence that shaped our species' diversity. Here we review notable recent advances in the detection, use, and understanding of population structure. Our work addresses multiple areas where substantial progress is being made: improved statistics and models for better capturing differentiation, admixture, and the spatial distribution of variation; computational speed-ups that allow methods to scale to modern data; and advances in haplotypic modeling that have wide ranging consequences for the analysis of population structure. We conclude by outlining four important open challenges: the limitations of discrete population models, uncertainty in individual origins, the incorporation of both fine-scale structure and ancient DNA in parametric models, and the development of efficient computational tools, particularly for haplotype-based methods. PMID- 27662063 TI - Delayed Neuraxial Hematoma in Parturient With Fontan Circulation Following Neuraxial Anesthesia for Cesarean Section. AB - OBJECTIVE: Neuraxial hematoma is a rare complication of spinal or epidural anesthesia. However, variable coagulation factor defects are relatively common in patients with Fontan circulation, and may predispose such patients to either increased risk of thrombosis or coagulopathy. These defects may indirectly increase their risk of neuraxial hematoma. CASE REPORT: We report a case of delayed neuraxial hematoma after the start of full-dose anticoagulation for pulmonary embolus on a postpartum patient with Fontan physiology who had continuous spinal anesthesia for cesarean delivery 4 days earlier. CONCLUSIONS: Parturients with single ventricle physiology present numerous challenges to balance, including pregnancy-related physiologic alterations in blood volume, cardiac output, systemic vascular resistance, oxygen consumption, and coagulation. Although neuraxial anesthesia is common in this population, it is not without risks. We report the circumstances surrounding a parturient with single ventricle physiology who experienced neuraxial hematoma 4 days after continuous spinal anesthesia despite adherence to accepted guidelines. Eighteen months after undergoing a cesarean section, she had a full recovery and returned to her baseline medical status. PMID- 27662064 TI - Necrotizing Fasciitis as a Complication of a Continuous Sciatic Nerve Catheter Using the Lateral Popliteal Approach. AB - OBJECTIVE: Necrotizing fasciitis is an infection of the soft tissue that is characterized by rapidly spreading inflammation and subsequent necrosis. It is a rare complication of peripheral nerve blocks. We report a rare case of necrotizing fasciitis after placement of a peripheral nerve catheter. CASE REPORT: A 58-year-old woman presented for an elective right second metatarsal resection and received a sciatic nerve catheter for postoperative pain control. On postoperative day 7, clinical examination and imaging supported the diagnosis of necrotizing fasciitis. CONCLUSIONS: Multiple reports have been published of necrotizing fasciitis after single-shot peripheral nerve block injections, neuraxial anesthesia, and intramuscular injections. This case highlights the potential for the rare complication of necrotizing fasciitis after peripheral nerve catheter placement. PMID- 27662065 TI - Local Infiltration of Analgesics at Surgical Wound to Reduce Postoperative Pain After Laparotomy in Rats. AB - BACKGROUND AND OBJECTIVES: There is an increasing use of local infiltration analgesia (LIA) to reduce postoperative pain. Despite widespread use of LIA, wide variations in drug combinations and concomitant use of systemic analgesics have made it difficult to determine the optimal drug combinations for LIA. Using a previously validated rat laparotomy model, the optimal LIA combination of medications to reduce postoperative pain was determined. METHODS: Laparotomy was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, and dexamethasone were injected over the sutured muscle wound before skin closing, and compared to saline (placebo). The same medications were injected systemically as controls. Postoperative pain was assessed by measuring spontaneous rearing activity. RESULTS: A high-dose 3-drug LIA combination (50 MUL of bupivacaine 0.75%, ketorolac 6.0 mg/mL, and dexamethasone 2.0 mg/mL) increased rearing (decreased pain) at 2 hours (P = 0.0032) postsurgery compared to saline. However, the same 3 drugs injected systemically had a similar analgesic effect (P = 0.0002). Bupivacaine 0.75% alone was not effective for LIA. When low-dose (9-fold reduction) 3-drug LIA combination was used, LIA increased rearing (P = 0.0034) whereas the same 3 drugs injected systemically had no effect. Low-dose LIA ketorolac/dexamethasone (2-drug combination) also increased rearing (P = 0.0393). CONCLUSIONS: Our animal study suggests that clinical trials with low-dose LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid may be useful for reducing postoperative pain after laparotomy. PMID- 27662066 TI - Reply to Dr Lessire et al. PMID- 27662067 TI - Local Anesthetic-Induced Myotoxicity After Continuous Adductor Canal Block. AB - OBJECTIVE: Local anesthetic-induced myotoxicity occurs consistently in animal models, yet is reported rarely in humans. Herein, we describe 3 sentinel cases of local anesthetic myotoxicity after continuous adductor canal block (ACB). CASE REPORT: Three patients underwent total knee arthroplasty that was managed with subarachnoid block plus ACB induced with 1.5% lidocaine or 1.5% mepivacaine bolus followed by 0.2% ropivacaine at 8 mL/h. Although initial postoperative recovery was normal, each patient on either postoperative day 1 or 2 developed progressive, profound weakness of the quadriceps muscles. Clinical course, imaging, and neurophysiologic studies were consistent with myositis. The patients experienced partial to full functional recovery over the ensuing weeks to months. CONCLUSIONS: Clinically apparent local anesthetic-induced myotoxicity has been documented rarely in humans undergoing non-ophthalmic surgery. We report 3 sentinel cases associated with continuous ACB. PMID- 27662068 TI - Correction to "Mass Spectrometric/Bioinformatic Identification of a Protein Subset That Characterizes the Cellular Activity of Anticancer Peptides". PMID- 27662069 TI - Plasmonic Imaging of Electrochemical Reactions of Single Nanoparticles. AB - Electrochemical reactions are involved in many natural phenomena, and are responsible for various applications, including energy conversion and storage, material processing and protection, and chemical detection and analysis. An electrochemical reaction is accompanied by electron transfer between a chemical species and an electrode. For this reason, it has been studied by measuring current, charge, or related electrical quantities. This approach has led to the development of various electrochemical methods, which have played an essential role in the understanding and applications of electrochemistry. While powerful, most of the traditional methods lack spatial and temporal resolutions desired for studying heterogeneous electrochemical reactions on electrode surfaces and in nanoscale materials. To overcome the limitations, scanning probe microscopes have been invented to map local electrochemical reactions with nanometer resolution. Examples include the scanning electrochemical microscope and scanning electrochemical cell microscope, which directly image local electrochemical reaction current using a scanning electrode or pipet. The use of a scanning probe in these microscopes provides high spatial resolution, but at the expense of temporal resolution and throughput. This Account discusses an alternative approach to study electrochemical reactions. Instead of measuring electron transfer electrically, it detects the accompanying changes in the reactant and product concentrations on the electrode surface optically via surface plasmon resonance (SPR). SPR is highly surface sensitive, and it provides quantitative information on the surface concentrations of reactants and products vs time and electrode potential, from which local reaction kinetics can be analyzed and quantified. The plasmonic approach allows imaging of local electrochemical reactions with high temporal resolution and sensitivity, making it attractive for studying electrochemical reactions in biological systems and nanoscale materials with high throughput. The plasmonic approach has two imaging modes: electrochemical current imaging and interfacial impedance imaging. The former images local electrochemical current associated with electrochemical reactions (faradic current), and the latter maps local interfacial impedance, including nonfaradic contributions (e.g., double layer charging). The plasmonic imaging technique can perform voltammetry (cyclic or square wave) in an analogous manner to the traditional electrochemical methods. It can also be integrated with bright field, dark field, and fluorescence imaging capabilities in one optical setup to provide additional capabilities. To date the plasmonic imaging technique has found various applications, including mapping of heterogeneous surface reactions, analysis of trace substances, detection of catalytic reactions, and measurement of graphene quantum capacitance. The plasmonic and other emerging optical imaging techniques (e.g., dark field and fluorescence microscopy), together with the scanning probe-based electrochemical imaging and single nanoparticle analysis techniques, provide new capabilities for one to study single nanoparticle electrochemistry with unprecedented spatial and temporal resolutions. In this Account, we focus on imaging of electrochemical reactions at single nanoparticles. PMID- 27662070 TI - Cooperative Binding of Cucurbit[n]urils and beta-Cyclodextrin to Heteroditopic Imidazolium-Based Guests. AB - Imidazolium-based guests containing two distinct binding epitopes are capable of binding beta-cyclodextrin and cucurbit[6/7]uril (CB) simultaneously to form heteroternary 1:1:1 inclusion complexes. In the final configuration, the hosts occupy binding sites disfavored in the binary complexes because of the chemically induced reorganization of the intermediate 1:1 aggregate. In addition, the reported guests are capable of binding two CBs to form either 1:2 or 1:1:1 ternary assemblies despite consisting of a single cationic moiety. Whereas the adamantane site binds CB solely via hydrophobic interactions, the CB unit at the butyl site is stabilized by a combination of hydrophobic and ion-dipole interactions. PMID- 27662071 TI - Nanodomain Engineering in Ferroelectric Capacitors with Graphene Electrodes. AB - Polarization switching in ferroelectric capacitors is typically realized by application of an electrical bias to the capacitor electrodes and occurs via a complex process of domain structure reorganization. As the domain evolution in real devices is governed by the distribution of the nucleation centers, obtaining a domain structure of a desired configuration by electrical pulsing is challenging, if not impossible. Recent discovery of polarization reversal via the flexoelectric effect has opened a possibility for deterministic control of polarization in ferroelectric capacitors. In this paper, we demonstrate mechanical writing of arbitrary-shaped nanoscale domains in thin-film ferroelectric capacitors with graphene electrodes facilitated by a strain gradient induced by a tip of an atomic force microscope (AFM). A phase-field modeling prediction of a strong effect of graphene thickness on the threshold load required to initiate mechanical switching has been confirmed experimentally. Deliberate voltage-free domain writing represents a viable approach for development of functional devices based on domain topology and electronic properties of the domains and domain walls. PMID- 27662072 TI - Alkali-Resistant Quasi-Solid-State Electrolyte for Stretchable Supercapacitors. AB - Research on stretchable energy-storage devices has been motivated by elastic electronics, and considerable research efforts have been devoted to the development of stretchable electrodes. However, stretchable electrolytes, another critical component in stretchable devices, have earned quite little attention, especially the alkali-resistant ones. Here, we reported a novel stretchable alkali-resistant electrolyte made of a polyolefin elastomer porous membrane supported potassium hydroxide-potassium polyacrylate (POE@KOH-PAAK). The as prepared electrolyte shows a negligible plastic deformation even after 1000 stretching cycles at a strain of 150% as well as a high conductivity of 0.14 S cm 1. It also exhibits excellent alkali resistance, which shows no obvious degradation of the mechanical performance after immersion in 2 M KOH for up to 2 weeks. To demonstrate its good properties, a high-performance stretchable supercapacitor is assembled using a carbon-nanotube-film-supported NiCo2O4 (CNT@NiCo2O4) as the cathode and Fe2O3 (CNT@Fe2O3) as the anode, proving great application promise of the stretchable alkali-resistant electrolyte in stretchable energy-storage devices. PMID- 27662073 TI - An increased expression profile of Th9/IL-9 correlated with Th17/IL-17 in patients with immune thrombocytopenia. AB - Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, characterized by dysregulation of cellular immunity. Th9 cells were recently identified as a new subtype of Th cells, characterized by preferential production of IL-9. Given the pleiotropic function of IL-9, Th9 cells are demonstrated to be involved in various autoimmune diseases. However, whether Th9 cells are involved in the pathogenesis of ITP remains unclear. In this study, 49 active ITP patients, 39 ITP with remission and 20 healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and controls for measuring Th9 and Th17 cells by flow cytometry. Meanwhile, RNA was isolated from PBMCs for the measurement of the mRNA level of PU.1, IRF4, BATF, and RORgammat by quantitative real-time PCR. Plasma levels of IL-9 and IL-17 were detected by ELISA. Our results showed that higher expressions of Th9, IL-9, and associated transcription factors (PU.1, IRF4, and BATF) were found in active ITP patients and restored to the normal level (except IL-9) in patients in remission. Meanwhile, Th9 cells and the IL-9 plasma level were positively correlated with Th17 cells and the IL-17 level in ITP patients, respectively. Moreover, a positive correlation of IRF4 or BATF with RORgammat was found. In conclusion, an aberrant expression profile of Th9/IL-9 was associated with pathogenesis of ITP possibly through cooperatively working with Th17/IL-17 and therapeutically targeting Th9/IL-9 might be a novel approach in the treatment of ITP. PMID- 27662074 TI - Neoliberal Optimism: Applying Market Techniques to Global Health. AB - Global health and neoliberalism are becoming increasingly intertwined as organizations utilize markets and profit motives to solve the traditional problems of poverty and population health. I use field work conducted over 14 months in a global health technology company to explore how the promise of neoliberalism re-envisions humanitarian efforts. In this company's vaccine refrigerator project, staff members expect their investors and their market to allow them to achieve scale and develop accountability to their users in developing countries. However, the translation of neoliberal techniques to the global health sphere falls short of the ideal, as profits are meager and purchasing power remains with donor organizations. The continued optimism in market principles amidst such a non-ideal market reveals the tenacious ideological commitment to neoliberalism in these global health projects. PMID- 27662075 TI - Dementia training programmes for staff working in general hospital settings - a systematic review of the literature. AB - OBJECTIVES: Although literature describing and evaluating training programmes in hospital settings increased in recent years, there are no reviews that summarise these programmes. This review sought to address this, by collecting the current evidence on dementia training programmes directed to staff working in general hospitals. METHOD: Literature from five databases were searched, based on a number of inclusion criteria. The selected studies were summarised and data was extracted and compared using narrative synthesis based on a set of pre-defined categories. Methodological quality was assessed. RESULTS: Fourteen peer-reviewed studies were identified with the majority being pre-test post-test investigations. No randomised controlled trials were found. Methodological quality was variable with selection bias being the major limitation. There was a great variability in the development and mode of delivery although, interdisciplinary ward based, tailor-made, short sessions using experiential and active learning were the most utilised. The majority of the studies mainly evaluated learning, with few studies evaluating changes in staff behaviour/practices and patients' outcomes. CONCLUSION: This review indicates that high quality studies are needed that especially evaluate staff behaviours and patient outcomes and their sustainability over time. It also highlights measures that could be used to develop and deliver training programmes in hospital settings. PMID- 27662077 TI - The Value of P. PMID- 27662076 TI - Cytokinesis defect in BY-2 cells caused by ATP-competitive kinase inhibitors. AB - Cytokinesis is last but not least in cell division as it completes the formation of the two cells. The main role in cell plate orientation and expansion have been assigned to microtubules and kinesin proteins. However, recently we reported severe cytokinesis defect in BY-2 cells not accompanied by changes in microtubules dynamics. Here we also confirmed that distribution of kinesin NACK1 is not the cause of cytokinesis defect. We further explored inhibition of the cell plate expansion by ATP-competitive inhibitors. Two different inhibitors, 5 Iodotubercidin and ML-7 resulted in a very similar phenotype, which indicates that they target same protein cascade. Interestingly, in our previous study we showed that 5-Iodotubercidin treatment affects concentration of actin filaments on the cell plate, while ML-7 is inhibitor of myosin light chain kinase. Although not directly, it indicates importance of actomyosin complex in plant cytokinesis. PMID- 27662078 TI - A commitment and vision to the future of the Journal of Neuroscience Research. PMID- 27662079 TI - On the perils of multiexponential fitting of diffusion MR data. PMID- 27662080 TI - Classification of Opium by UPLC-Q-TOF Analysis of Principal and Minor Alkaloids. AB - Opium is the raw material for the production of heroin, and the characterization of opium seizures through laboratory analysis is a valuable tool for law enforcement agencies to trace clandestine opium production and trafficking. In this work, a method for opium profiling based on the relative content of five principal and 14 minor opium alkaloids was developed and validated. UPLC-Q-TOF was adopted in alkaloid analysis for its high selectivity and sensitivity, which facilitated the sample preparation and testing. The authentic sample set consisted of 100 "Myanmar" and 45 "Afghanistan" opium seizures; based on the data set of the 19 alkaloid variables in them, a partial least squares discriminant analysis classification model was successfully achieved. Minor alkaloids were found to be vitally important for opium profiling, although combined use of both principal and minor alkaloids resulted in the best geographical classification result. The developed method realized a simple and accurate way to differentiate opium from Myanmar and Afghanistan, which may find wide application in forensic laboratories. PMID- 27662081 TI - When a Stomach Bug Comes Calling. PMID- 27662082 TI - A New Handle for a Hot Topic: Genetic Markers for Warm-Sensing. AB - Stepping out of an aggressively air-conditioned building into the sweltering heat evokes a number of thermoregulatory responses, both autonomic (sweating) and behavioral (peeling off a layer of clothing or seeking an iced beverage). Just as we come out of the hottest part of the summer, a study by Tan and colleagues provides an exciting breakthrough in our ability to study the neural mechanisms of keeping cool when it's hot. PMID- 27662083 TI - Lifting the Differentiation Embargo. AB - Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers. PMID- 27662085 TI - sRNA-Mediated Control of Transcription Termination in E. coli. AB - Bacterial small RNAs (sRNAs) have been implicated in various aspects of post transcriptional gene regulation. Here, we demonstrate that sRNAs also act at the level of transcription termination. We use the rpoS gene, which encodes a general stress sigma factor sigma(S), as a model system, and show that sRNAs DsrA, ArcZ, and RprA bind the rpoS 5'UTR to suppress premature Rho-dependent transcription termination, both in vitro and in vivo. sRNA-mediated antitermination markedly stimulates transcription of rpoS during the transition to the stationary phase of growth, thereby facilitating a rapid adjustment of bacteria to global metabolic changes. Next generation RNA sequencing and bioinformatic analysis indicate that Rho functions as a global "attenuator" of transcription, acting at the 5'UTR of hundreds of bacterial genes, and that its suppression by sRNAs is a widespread mode of bacterial gene regulation. PMID- 27662084 TI - Central Control Circuit for Context-Dependent Micturition. AB - Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here, we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) is electrophysiologically distinct from their Crh negative neighbors and sends glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context dependent micturition behavior. PMID- 27662086 TI - Large-Scale Movements of IF3 and tRNA during Bacterial Translation Initiation. AB - In bacterial translational initiation, three initiation factors (IFs 1-3) enable the selection of initiator tRNA and the start codon in the P site of the 30S ribosomal subunit. Here, we report 11 single-particle cryo-electron microscopy (cryoEM) reconstructions of the complex of bacterial 30S subunit with initiator tRNA, mRNA, and IFs 1-3, representing different steps along the initiation pathway. IF1 provides key anchoring points for IF2 and IF3, thereby enhancing their activities. IF2 positions a domain in an extended conformation appropriate for capturing the formylmethionyl moiety charged on tRNA. IF3 and tRNA undergo large conformational changes to facilitate the accommodation of the formylmethionyl-tRNA (fMet-tRNA(fMet)) into the P site for start codon recognition. PMID- 27662087 TI - Structural Basis for Gating and Activation of RyR1. AB - The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca(2+)) release channel required for skeletal muscle contraction. Here, we present cryo-EM reconstructions of RyR1 in multiple functional states revealing the structural basis of channel gating and ligand-dependent activation. Binding sites for the channel activators Ca(2+), ATP, and caffeine were identified at interdomain interfaces of the C-terminal domain. Either ATP or Ca(2+) alone induces conformational changes in the cytoplasmic assembly ("priming"), without pore dilation. In contrast, in the presence of all three activating ligands, high resolution reconstructions of open and closed states of RyR1 were obtained from the same sample, enabling analyses of conformational changes associated with gating. Gating involves global conformational changes in the cytosolic assembly accompanied by local changes in the transmembrane domain, which include bending of the S6 transmembrane segment and consequent pore dilation, displacement, and deformation of the S4-S5 linker and conformational changes in the pseudo-voltage sensor domain. PMID- 27662088 TI - Structured States of Disordered Proteins from Genomic Sequences. AB - Protein flexibility ranges from simple hinge movements to functional disorder. Around half of all human proteins contain apparently disordered regions with little 3D or functional information, and many of these proteins are associated with disease. Building on the evolutionary couplings approach previously successful in predicting 3D states of ordered proteins and RNA, we developed a method to predict the potential for ordered states for all apparently disordered proteins with sufficiently rich evolutionary information. The approach is highly accurate (79%) for residue interactions as tested in more than 60 known disordered regions captured in a bound or specific condition. Assessing the potential for structure of more than 1,000 apparently disordered regions of human proteins reveals a continuum of structural order with at least 50% with clear propensity for three- or two-dimensional states. Co-evolutionary constraints reveal hitherto unseen structures of functional importance in apparently disordered proteins. PMID- 27662089 TI - Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation. AB - Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition. PMID- 27662090 TI - Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing. AB - Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine. PMID- 27662092 TI - Portable, On-Demand Biomolecular Manufacturing. AB - Synthetic biology uses living cells as molecular foundries for the biosynthesis of drugs, therapeutic proteins, and other commodities. However, the need for specialized equipment and refrigeration for production and distribution poses a challenge for the delivery of these technologies to the field and to low-resource areas. Here, we present a portable platform that provides the means for on-site, on-demand manufacturing of therapeutics and biomolecules. This flexible system is based on reaction pellets composed of freeze-dried, cell-free transcription and translation machinery, which can be easily hydrated and utilized for biosynthesis through the addition of DNA encoding the desired output. We demonstrate this approach with the manufacture and functional validation of antimicrobial peptides and vaccines and present combinatorial methods for the production of antibody conjugates and small molecules. This synthetic biology platform resolves important practical limitations in the production and distribution of therapeutics and molecular tools, both to the developed and developing world. PMID- 27662094 TI - Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos. PMID- 27662091 TI - Editing DNA Methylation in the Mammalian Genome. AB - Mammalian DNA methylation is a critical epigenetic mechanism orchestrating gene expression networks in many biological processes. However, investigation of the functions of specific methylation events remains challenging. Here, we demonstrate that fusion of Tet1 or Dnmt3a with a catalytically inactive Cas9 (dCas9) enables targeted DNA methylation editing. Targeting of the dCas9-Tet1 or Dnmt3a fusion protein to methylated or unmethylated promoter sequences caused activation or silencing, respectively, of an endogenous reporter. Targeted demethylation of the BDNF promoter IV or the MyoD distal enhancer by dCas9-Tet1 induced BDNF expression in post-mitotic neurons or activated MyoD facilitating reprogramming of fibroblasts into myoblasts, respectively. Targeted de novo methylation of a CTCF loop anchor site by dCas9-Dnmt3a blocked CTCF binding and interfered with DNA looping, causing altered gene expression in the neighboring loop. Finally, we show that these tools can edit DNA methylation in mice, demonstrating their wide utility for functional studies of epigenetic regulation. PMID- 27662095 TI - Timeline: Cellular Oxygen Sensing. AB - Since the 1950s, researchers have recognized that red blood cell numbers expand or contract as needed, according to the amount of available oxygen. The later discoveries that erythropoietin and VEGF levels adapt to oxygen levels launched a new field aimed at understanding how cells sense and respond to normal- and low oxygen environments. The 2016 Albert Lasker Basic Medical Research Award recognizes key discoveries about this global oxygen sensing pathway and its impacts on pathogenesis, including cancer and inflammation. PMID- 27662093 TI - Evidence for Pro-angiogenic Functions of VEGF-Ax. AB - The VEGF-A isoforms play a crucial role in vascular development, and the VEGF signaling pathway is a clinically validated therapeutic target for several pathological conditions. Alternative mRNA splicing leads to the generation of multiple VEGF-A isoforms, including VEGF165. A recent study reported the presence of another isoform, VEGF-Ax, arising from programmed readthrough translation. Compared to VEGF165, VEGF-Ax has a 22-amino-acid extension in the COOH terminus and has been reported to function as a negative regulator of VEGF signaling in endothelial cells, with potent anti-angiogenic effects. Here, we show that, contrary to the earlier report, VEGF-Ax stimulates endothelial cell mitogenesis, angiogenesis, as well as vascular permeability. Accordingly, VEGF-Ax induces phosphorylation of key tyrosine residues in VEGFR-2. Notably, VEGF-Ax was less potent than VEGF165, consistent with its impaired binding to the VEGF co-receptor neuropilin-1. PMID- 27662096 TI - Timeline: Targeted Treatment of Hepatitis C Virus. AB - Chronic hepatitis C virus infection can cause liver cirrhosis and cancer, and early treatment options were non-specific and could be toxic. Work aimed at elucidating the viral life cycle has led to better treatment options through the development of direct-acting antivirals, as exemplified by the work of Ralf Bartenschlager, Charles Rice, and Michael Sofia who have received the Lasker~DeBakey Clinical Medical Research Award for their work on this effort. Key events in understanding HCV replication and development of direct-acting antivirals are shown in this Timeline. PMID- 27662097 TI - Developing Intense Blue and Magenta Colors in alpha-LiZnBO3 : The Role of 3d Metal Substitution and Coordination. AB - We describe the synthesis, crystal structures, and optical absorption spectra/colors of 3d-transition-metal-substituted alpha-LiZnBO3 derivatives: alpha-LiZn1-x MIIx BO3 (MII =CoII (0= 25; 12-20 weeks gestation) reported LOC before and during early pregnancy using the Eating Disorder Examination, which was adapted for administration in pregnancy. Women self-reported depressive symptoms and stress during early pregnancy. RESULTS: Twenty-eight percent (n = 56) of women reported LOC before or during early pregnancy: 14.5% (n = 29) reported LOC incidence during early pregnancy, 9.5% (n = 19) reported LOC persistence from prepregnancy to early pregnancy, and 4.0% (n = 8) reported LOC prepregnancy only. Women with LOC reported more depressive symptoms and stress than did those without. Women with LOC persistence reported clinically significant depressive symptoms and elevated stress. Levels of depressive symptoms and stress differed between women with LOC persistence and those without LOC (ps < 0.05). DISCUSSION: LOC during pregnancy was prevalent and associated with distress, particularly when present before and during pregnancy. Among women with LOC, few reported remission, but one-half reported onset during early pregnancy. Longitudinal studies are needed among mothers with overweight/obesity to identify patterns of LOC throughout pregnancy and how LOC affects perinatal outcomes. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:582-586). PMID- 27662103 TI - Novel insights into the diagnostic and therapeutic challenges of the CFTR metabolic syndrome/CF screen positive indeterminate diagnosis. AB - The growth of cystic fibrosis newborn screening (CF NBS) has led to an increased number of infants with a positive NBS test but inconclusive CF diagnostic testing. In the USA this condition is called CFTR related metabolic syndrome (CRMS), while in Europe the term CF screen positive, inconclusive diagnosis (CFSPID) is used. Recent advances in CF genetics and epidemiologic studies of CRMS/CFSPID have provided new insights into the prevalence and outcomes associated with this condition. Pediatr Pulmonol. 2016;51:S45-S48. (c) 2016 Wiley Periodicals, Inc. PMID- 27662104 TI - Early detection and sensitive monitoring of CF lung disease: Prospects of improved and safer imaging. AB - Recent imaging studies using chest computed tomography (CT) in presymptomatic infants and young children with cystic fibrosis (CF) diagnosed by newborn screening presented compelling evidence of early onset and progression of structural lung damage in CF. These data argue persuasively that non-invasive outcome measures for early detection and sensitive monitoring of lung disease applicable in the clinical setting will be instrumental for further improvement of clinical care and the development of early intervention therapies that have the potential to prevent irreversible lung damage. In this context, the use of CT imaging for early detection and long-term monitoring has the disadvantage of the risk to induce malignancies due to cumulating ionizing radiation exposure. More recently, magnetic resonance imaging (MRI) has emerged as an alternative radiation-free imaging technique for quantitative assessment of CF lung disease. In addition to structural lung damage, chest MRI enables non-invasive assessment of abnormalities in lung perfusion and ventilation characteristically associated with mucus plugging in CF lung disease. Here, we review recent developments and the prospects of MRI for improved and safer imaging with a focus on recent studies that support its utility as a sensitive non-invasive outcome measure of early lung disease in young children with CF. Pediatr Pulmonol. 2016;51:S49-S60. (c) 2016 Wiley Periodicals, Inc. PMID- 27662105 TI - Genetic medicines for CF: Hype versus reality. AB - Since identification of the CFTR gene over 25 years ago, gene therapy for cystic fibrosis (CF) has been actively developed. More recently gene therapy has been joined by other forms of "genetic medicines" including mRNA delivery, as well as genome editing and mRNA repair-based strategies. Proof-of-concept that gene therapy can stabilize the progression of CF lung disease has recently been established in a Phase IIb trial. An early phase study to assess the safety and explore efficacy of CFTR mRNA repair is ongoing, while mRNA delivery and genome editing-based strategies are currently at the pre-clinical phase of development. This review has been written jointly by some of those involved in the various CF "genetic medicine" fields and will summarize the current state-of-the-art, as well as discuss future developments. Where applicable, it highlights common problems faced by each of the strategies, and also tries to highlight where a specific strategy may have an advantage on the pathway to clinical translation. We hope that this review will contribute to the ongoing discussion about the hype versus reality of genetic medicine-based treatment approaches in CF. Pediatr Pulmonol. 2016;51:S5-S17. (c) 2016 Wiley Periodicals, Inc. PMID- 27662106 TI - Therapeutic challenges posed by critical drug-drug interactions in cystic fibrosis. AB - This review seeks to re-introduce cystic fibrosis (CF) clinicians to the pharmacology of drug-drug interactions among medications commonly used in CF and provide a framework for understanding these interactions among medications outside the scope of this discussion. We here focus on drugs impacted by the cytochrome P-450 (CYP450) enzyme system and on interactions involving antimicrobials, psychotropic medications, and cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Particular attention is needed when prescribing rifampin, azole antifungals and the CFTR modulators, ivacaftor, and lumacaftor/ivacaftor, in combination with other medications. The complexities of these interactions provide a strong rationale for case management by pharmacists and pharmacologists as a routine part of CF care. Pediatr Pulmonol. 2016;51:S61 S70. (c) 2016 Wiley Periodicals, Inc. PMID- 27662102 TI - The CF gastrointestinal microbiome: Structure and clinical impact. AB - The gastrointestinal (GI) microbiome is shaped by host diet, immunity, and other physicochemical characteristics of the GI tract, and perturbations such as antibiotic treatments can lead to persistent changes in microbial constituency and function. These GI microbes also play critical roles in host nutrition and health. A growing body of evidence suggests that the GI microbiome in people with CF is altered, and that these dysbioses contribute to disease manifestations in many organs, both within and beyond the GI tract. Therapies that people with CF receive, even those targeting the respiratory tract, may impact the CF GI microbiome in ways that can influence the outcome of treatment. These new perspectives on the microbial contents of the CF intestine offer new opportunities for preventing a variety of CF-associated disorders. Pediatr Pulmonol. 2016;51:S35-S44. (c) 2016 Wiley Periodicals, Inc. PMID- 27662107 TI - Maintaining mental health and function for the long run in cystic fibrosis. AB - Research shows that individuals with cystic fibrosis (CF) and their families experience significant emotional morbidity. In addition to distress, worry, and grief, high rates of clinically significant symptoms of depression and anxiety have been found in both individuals with CF and parents. These disorders have a major impact on the person's functioning, and that of their family, and adversely impact the capacity to cope with the burden of CF and adhere to prescribed treatments. Despite growing recognition that mental health care is an essential component of comprehensive CF care, evidence suggests many patients and their families do not receive needed support and mental health interventions. Clinical practice guidelines for screening and treating depression and anxiety in individuals with CF have been developed by The Cystic Fibrosis Foundation and the European Cystic Fibrosis Society in response to this need. This review highlights that the optimum care for individuals with CF and their families incorporates mental health in routine CF care. Addressing mental health could substantially improve physical and mental health outcomes and the functioning of individuals with CF and their families. Pediatr Pulmonol. 2016;51:S71-S78. (c) 2016 Wiley Periodicals, Inc. PMID- 27662108 TI - Accurate classification of brain gliomas by discriminate dictionary learning based on projective dictionary pair learning of proton magnetic resonance spectra. AB - Proton magnetic resonance spectroscopy is a powerful noninvasive technique that complements the structural images of cMRI, which aids biomedical and clinical researches, by identifying and visualizing the compositions of various metabolites within the tissues of interest. However, accurate classification of proton magnetic resonance spectroscopy is still a challenging issue in clinics due to low signal-to-noise ratio, overlapping peaks of metabolites, and the presence of background macromolecules. This paper evaluates the performance of a discriminate dictionary learning classifiers based on projective dictionary pair learning method for brain gliomas proton magnetic resonance spectroscopy spectra classification task, and the result were compared with the sub-dictionary learning methods. The proton magnetic resonance spectroscopy data contain a total of 150 spectra (74 healthy, 23 grade II, 23 grade III, and 30 grade IV) from two databases. The datasets from both databases were first coupled together, followed by column normalization. The Kennard-Stone algorithm was used to split the datasets into its training and test sets. Performance comparison based on the overall accuracy, sensitivity, specificity, and precision was conducted. Based on the overall accuracy of our classification scheme, the dictionary pair learning method was found to outperform the sub-dictionary learning methods 97.78% compared with 68.89%, respectively. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27662109 TI - Modified niche optima and breadths explain the historical contingency of bacterial community responses to eutrophication in coastal sediments. AB - Previous studies have shown that the response of bacterial communities to disturbances depends on their environmental history. Historically fluctuating habitats host communities that respond better to disturbance than communities of historically stable habitats. However, the exact ecological mechanism that drives this dependency remains unknown. Here, we experimentally demonstrate that modifications of niche optima and niche breadths of the community members are driving this dependency of bacterial responses to past environmental conditions. First, we develop a novel, simple method to calculate the niche optima and breadths of bacterial taxa regarding single environmental gradients. Then, we test this method on sediment bacterial communities of three habitats, one historically stable and less loaded and two historically more variable and more loaded habitats in terms of historical chlorophyll-alpha water concentration, that we subject to hypoxia via organic matter addition ex situ. We find that communities containing bacterial taxa differently adapted to hypoxia show different structural and functional responses, depending on the sediment's environmental history. Specifically, in the historically less fluctuating and loaded sediments where we find more taxa poorly adapted to hypoxic conditions, communities change a lot over time and organic matter is not degraded efficiently. The opposite is true for the historically more fluctuating and loaded sediments where we find more taxa well adapted to hypoxia. Based on the community responses observed here, we also propose an alternative calculation of community resistance that takes into account how rapidly the communities respond to disturbances and not just the initial and final states of the community. PMID- 27662110 TI - Potential of Salvinia auriculata biomass as biosorbent of the Cr(III): directed chemical treatment, modeling and sorption mechanism study. AB - In this work, the mechanism of the Cr(III) sorption by Salvinia auriculata biosorbent was studied in two stages. To understand the influence of the sorption parameters on the Cr(III) uptake, preliminary tests were performed. First, S. auriculata biomass was separately treated with base and acid solutions. Second, acid and base treatment of samples was performed based on the knowledge data base of our group. It was achieved a higher Cr(III) sorption capacity above 15 mg g-1 as associated to an increase of the micro-pores specific area and biosorbent volume. The obtained kinetic data of raw and treated biosorbents were well described by the intra-particle diffusion model. In this model, Cr(III) adsorption onto treated biomass is progressively improved with appearing of different mass transfer zones from out layer up to micro-porous layers. The equilibrium data of raw biomass were best described by the Langmuir isotherm, whereas the equilibrium data of the treated biomass were best fit by a combination of both Langmuir and Dubinin-Radushkevich isotherms. At low concentrations the adsorption most likely occurred on the outer monolayer, as proposed by the Langmuir model, followed by the adsorption on the micro-porous layers, as validated by the Dubinin-Radushkevich isotherm. PMID- 27662111 TI - Emission of low-energy positronium from alkali-metal coated single-crystal tungsten surfaces. AB - We have measured the time-of-flight of ortho-positronium emitted from Cs-, Na- and Li-coated single-crystal tungsten surfaces. The data obtained after the coating show a new positronium energy component with a specific energy loss in addition to the component whose emission energy is simply determined by the positron and the electron work functions. We suggest that this new component is attributed to the formation of positronium accompanied by inter-band transition and/or surface plasmon excitation at the surfaces. PMID- 27662112 TI - The demand for speech pathology services for children: Do we need more or just different? AB - An inability or difficulty communicating can have a profound impact on a child's future ability to participate in society as a productive adult. Over the past few years the number of interventions for children with speech and language problems has almost doubled; the majority are targeted interventions delivered by speech pathologists. In this paper we examine the distribution of speech pathology services in metropolitan Melbourne and how these are aligned with need as defined by vulnerability in language and social disadvantage. We identified three times as many private sector services compared to public services for the 0-5 year age group. Overall there was poorer availability of services in some of the most vulnerable areas. The profound and long-term impact of impoverished childhood language, coupled with the considerable limitations on public spending, provide a strong impetus to deliver more equitably distributed speech pathology services. PMID- 27662113 TI - Anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex enhances emotion recognition in depressed patients and controls. AB - INTRODUCTION: Transcranial direct current stimulation (tDCS) can enhance a range of neuropsychological functions but its efficacy in addressing clinically significant emotion recognition deficits associated with depression is largely untested. METHOD: A randomized crossover placebo controlled study was used to investigate the effects of tDCS over the left dorsolateral prefrontal cortex (L DLPFC) on a range of neuropsychological variables associated with depression as well as neural activity in the associated brain region. A series of computerized tests was administered to clinical (n = 17) and control groups (n = 20) during sham and anodal (1.5 mA) stimulation. RESULTS: Anodal tDCS led to a significant main effect for overall emotion recognition (p = .02), with a significant improvement in the control group (p = .04). Recognition of disgust was significantly greater in the clinical group (p = .01). Recognition of anger was significantly improved for the clinical group (p = .04) during anodal stimulation. Differences between groups for each of the six emotions at varying levels of expression found that at 40% during anodal stimulation, happy recognition significantly improved for the clinical group (p = .01). Anger recognition at 80% during anodal stimulation significantly improved for the clinical group (p = .02). These improvements were observed in the absence of any change in psychomotor speed or trail making ability during anodal stimulation. Working memory significantly improved during anodal stimulation for the clinical group but not for controls (p = .03). CONCLUSIONS: The tentative findings of this study indicate that tDCS can have a neuromodulatory effect on a range of neuropsychological variables. However, it is clear that there was a wide variation in responses to tDCS and that individual difference and different approaches to testing and stimulation have a significant impact on final outcomes. Nonetheless, tDCS remains a promising tool for future neuropsychological research. PMID- 27662114 TI - The Impacts of Social Support and Cognitive Function on Depression among Community-Dwelling Older Japanese Americans. AB - Research has demonstrated a relationship between social support, cognitive function, and depression among older adults, yet fewer studies have explored this association with Japanese American elders. This study aims to examine depression and describe its relationship with social support, cognitive function, and socioeconomic condition among Japanese American elders. A cross-sectional study of 205 Japanese American elders was conducted in Honolulu and Los Angeles County. A hierarchical regression model was used with depression as a dependent variable and with independent variables such as social support, cognitive function, and socioeconomic status. The study found that social support and cognitive function were significantly associated with depression for Japanese American elders. Also age and education were significantly associated with depression. Based on the findings, the study indicates the importance of developing preventive strategies to reduce the depression issue using culturally tailored programs to the study population. PMID- 27662115 TI - Pharmacokinetic characterization of anhuienoside C and its deglycosylated metabolites in rats. AB - 1. Anhuienoside C (AC), a triterpenoid saponin derived from the traditional Chinese medicine (TCM) "Di Wu", has significant anti-inflammatory and anti rheumatoid arthritis activities. Here we aimed to characterize the pharmacokinetics of AC and its deglycosylated metabolites in rats. 2. AC was administered to rats by intravenous injection or oral gavage. AC and its four deglycosylated metabolites (M1, M2, M3 and M4) in biological samples were quantified using a UPLC-QTOF/MS system. The pharmacokinetic data were analyzed by compartmental modeling. The metabolism of M1, M2, M3 and M4 was determined using rat liver microsomes (RLM) and rat intestine microsomes (RIM). The intestinal permeabilities of AC and its metabolites were evaluated using Parallel artificial membrane permeability assay (PAMPA) and MDR1-transfected Madin-Darby canine kidney cell (MDCK-MDR1) cell model. 3. AC pharmacokinetics was well described by the one-compartment model. The oral bioavailability of AC was exceedingly low (F = 0.03%). Consistently, AC was poorly distributed (< 0.08 MUM) in major organs including the heart, liver, spleen, lung and kidney after oral uptake. Three of four deglycosylated metabolites (M2, M3, and M4) underwent further metabolism in RLM, generating five, two and five oxidized products, respectively. Both PAMPA and MDCK-MDR1 experiments showed that AC and its metabolites were poorly permeable. Furthermore, the net flux ratios derived from MDCK-MDR1 versus wild type MDCK cells were, respectively 1.3, 1.5, 0.7, 1.2 and 0.6 for AC, M1, M2, M3 and M4, suggesting that these compounds were non-substrates of P-glycoprotein. 4. In conclusion, extensive pre-systemic metabolism and poor permeability were the main causes of low systemic exposures of oral AC and its four metabolites. PMID- 27662116 TI - Effects of Freeze-Thaw and Storage on Enzymatic Activities, Protein Oxidative Damage, and Immunocontent of the Blood, Liver, and Brain of Rats. AB - Most scientific studies are too long to be conducted in a single day or even in a few days. Thus, there is a need to store samples for subsequent investigations. There is sparse information about specific sample storage protocols that minimize analytical error and variability in evaluations of redox parameters. Therefore, the effects of storage temperature and freezing time on enzymatic activities, protein oxidative damage, and CAT (catalase) and SOD1 (superoxide dismutase) immunocontent of blood, liver, and brain from rats were determined for two different sample forms (frozen homogenized tissue or frozen intact tissue). Superoxide dismutase activity was drastically decreased in blood and liver with an increase in freezing time, but not in brain. Catalase activity showed a decrease only in intact liver at -20 and -80 degrees C. In contrast, in blood it showed an increase in intact tissue at -20 and -80 degrees C. Reduced thiol groups generally decreased with freezing time, but showed an increase in intact blood at -20 and -80 degrees C, probably because of color interference. Carbonyl groups in homogenized liver and brain, and in intact blood (except at 80 degrees C) drastically increased with freezing time. Freezing time did not modulate the immunocontent of CAT and SOD1 levels in any tissue. In conclusion, our results indicate that storage at -20 degrees C affects redox parameters more than storage at -80 degrees C. Storage for a long time may compromise the samples, leading to changing parameters due to oxidative stress. Thus, we suggest processing the samples as soon as possible. However, if this is not possible, then material can be aliquoted into different tubes to prevent the effect of refreezing of samples. PMID- 27662117 TI - Implantable Medical Device Website Efficacy in Informing Consumers Weighing Benefits/Risks of Health Care Options. AB - As more individuals turn to the Internet for health-related information and technology increases the availability and use of implantable medical devices (IMDs), the websites marketing these devices will increase. Healthy People 2020 mandates increased understandability and usability of health-related websites. This project used social cognitive theory (SCT) and health literacy constructs from the Institute of Medicine and National Institutes of Health to analyze eight IMD websites. Despite current recommendations, none of the websites considered for this study offered content of an appropriate reading level in conjunction with the United States average of eighth grade, and 75% of the sites failed to satisfy more than one health literacy construct. Most of the websites lacked many of the SCT constructs. More attention is needed to improve the usability of these and future IMD websites to simultaneously meet the goal of marketing IMDs and the Healthy People 2020 goals to educate patients and promote public health. PMID- 27662119 TI - ? AB - There can be few developments that have been so painfully slow and over-discussed as performance related pay in the NHS. Yet the time and the talking has done little to aid clarity and understanding of the issue. It could well be that after a record gestation period, PRP proves to be a phantom pregnancy. PMID- 27662120 TI - UKCC staff 'insulted' by report. AB - Nursing's governing body was plunged into crisis last week when senior officers rejected the findings of the investigation into allegations of mismanagement by UKCC Registrar Colin Ralph. PMID- 27662118 TI - Justify Your Answer: The Role of Written Think Aloud in Script Concordance Testing. AB - : Construct: Clinical reasoning assessment is a growing area of interest in the medical education literature. Script concordance testing (SCT) evaluates clinical reasoning in conditions of uncertainty and has emerged as an innovative tool in the domain of clinical reasoning assessment. SCT quantifies the degree of concordance between a learner and an experienced clinician and attempts to capture the breadth of responses of expert clinicians, acknowledging the significant yet acceptable variation in practice under situations of uncertainty. BACKGROUND: SCT has been shown to be a valid and reliable clinical reasoning assessment tool. However, as SCT provides only quantitative information, it may not provide a complete assessment of clinical reasoning. APPROACH: Think aloud (TA) is a qualitative research tool used in clinical reasoning assessment in which learners verbalize their thought process around an assigned task. This study explores the use of TA, in the form of written reflection, in SCT to assess resident clinical reasoning, hypothesizing that the information obtained from the written TA would enrich the quantitative data obtained through SCT. Ninety-one pediatric postgraduate trainees and 21 pediatricians from 4 Canadian training centers completed an online test consisting of 24 SCT cases immediately followed by retrospective written TA. Six of 24 cases were selected to gather TA data. These cases were chosen to allow all phases of clinical decision making (diagnosis, investigation, and treatment) to be represented in the TA data. Inductive thematic analysis was employed when systematically reviewing TA responses. RESULTS: Three main benefits of adding written TA to SCT were identified: (a) uncovering instances of incorrect clinical reasoning despite a correct SCT response, (b) revealing sound clinical reasoning in the context of a suboptimal SCT response, and (c) detecting question misinterpretation. CONCLUSIONS: Written TA can optimize SCT by demonstrating when correct examinee responses are based on guessing or uncertainty rather than robust clinical rationale. TA can also enhance SCT by allowing examinees to provide justification for responses that otherwise would have been considered incorrect and by identifying questions that are frequently misinterpreted to avoid including them in future examinations. TA also has significant value in differentiating between acceptable variations in expert clinician responses and deviance associated with faulty rationale or question misinterpretation; this could improve SCT reliability. A written TA protocol appears to be a valuable tool to assess trainees' clinical reasoning and can strengthen the quantitative assessment provided by SCT. PMID- 27662121 TI - Scottish report into research funds imminent. AB - An NHS Scotland report to MPs on the award of nursing research grants totalling more than L1m is to be published next week. PMID- 27662122 TI - Abandon Project 2000 says professor. AB - Project 2000 should be abandoned and replaced by a training system which produces nurses with generic qualifications, controversial health academic Roger Dyson said last week. PMID- 27662123 TI - Shortage of health visitors leaving many children at risk. AB - The Health Visitors' Association has called on the Government to double the number of health visitors by 2004. PMID- 27662124 TI - Report criticises professional insensitivity when dealing with children's disabilities. AB - The Spastics Society has called for explicit national guidelines on how health professionals divulge news of a child's disability to parents. PMID- 27662125 TI - Skill mix reviews exposed as cost cutting schemes. AB - Skill mix reviews are being used as clandestine cost cutting exercises, Unison warned last week as it launched guidelines for trusts to follow. PMID- 27662126 TI - Equality code for maternity services. AB - Midwives have welcomed a code of practice to improve maternity services for ethnic minority mothers launched by the Commission for Racial Equality last week. PMID- 27662127 TI - ? AB - Time warp: The cast of the Rocky Horror Picture Show were among the stars who celebrated 60 years of the British Diabetic Association at the Cafe Royal in London last week. The event was organised to coincide with National Diabetes Week. PMID- 27662129 TI - Unions to continue legal battle over compensation. AB - The House of Lords has rejected the Government's controversial changes to the Criminal Justice Bill, which would see nurses injured as a result of criminal acts at work receiving far less compensation. PMID- 27662130 TI - MPs urged to back purchasing role. AB - All purchasing authorities should have a nurse on their executive board, the Royal College of Nursing insisted last week at a hearing of the Commons health committee. PMID- 27662132 TI - Health reforms used as excuse for job cuts. AB - A growing number of US hospitals are using proposed health care reforms as an excuse to lay off staff, an education session on 'downsizing' heard. Carol Alexander, an administrative nursing director from Denver, said the ANA was concerned at the number of institutions taking 'precipitous' action ahead of any reforms being approved. There were 'disturbing reports' of a growing number of changes in workforce practice. blamed, in many cases, on health care reform, she said. PMID- 27662131 TI - Canada's GPs fight off threat by nurses. AB - Doctors were so threatened by the emergence of nurse practitioners in Canada that they mounted a successful campaign to see them off. PMID- 27662133 TI - Hillary Clinton call to support reforms. AB - Failure to implement US health care reforms could mean restriction or even elimination of the nurse's role, First Lady Hillary Clinton told the convention. PMID- 27662135 TI - RCN chief criticises 'totally shocking' health care system. AB - The USA health care system is 'totally shocking' to UK nurses, RCN General Secretary Christine Hancock told the convention. 'It's almost incomprehensible that millions of people don't have access to health care. It's like not having fresh air to breathe or clean water to drink', she said. PMID- 27662134 TI - American nurses association convention, June 10-15, san antonio, texas. AB - American nurses gathered in Texas last week for the ANA Biennial Convention, with its theme 'Nurses: charting the course for a healthy nation'. Health care reform, the threat of redundancy, and skill mix dominated the debate as in the UK. PMID- 27662136 TI - Firearms now a major cause of child death. AB - An epidemic of handgun violence in the United States has led the American Nurses Association to step up its campaign against firearm sales and availability. PMID- 27662137 TI - New guidelines advise US nurses to avoid euthanasia issues. AB - Nurses should not take part in euthanasia or assisted suicide, according to new advice being drawn up by the American Nurses Association. PMID- 27662138 TI - Fears over unlicensed nurses. AB - American nurses facing similar problems to their British counterparts, including increased workloads, skill mix reviews and reduced staffing levels have warned patient care will suffer if the trend continues. PMID- 27662139 TI - ANA honours reinstated lesbian nurse. AB - The American Nurses' Association has honoured a military nurse, decorated in Vietnam, who has been reinstated to the National Guard two years after being dismissed because she was a lesbian. PMID- 27662140 TI - Fear over UKCC report's impact. AB - Nursing home managers have reacted angrily to the UK Central Council's controversial report on standards in nursing homes. While the report's recommendations have been widely welcomed, both Government and the Registered Nursing Homes Association questioned the figures the report based its findings on. PMID- 27662141 TI - Special group for day care nurses. AB - A special interest group for day care nurses has been set up by the Royal College of Nursing in the north west of England. PMID- 27662142 TI - ? AB - B-tea: Actress Maureen Lipman launched the charity Fight for Sight's 'tea fest' programme at the Waldorf Hotel in London last week. Tea drinkers are being urged to organise fund-raising tea parties to help research into the most common causes of blindness. PMID- 27662143 TI - Parliament. AB - * Investigations into fears that childhood cancers may be linked to electromagnetic fields are being sought by government advisers. PMID- 27662144 TI - Profit-related pay alternative. AB - The case for performance-related pay for nurses and other staff providing direct care to patients has still not been proven, the human resources director of a Kent trust told the conference. PMID- 27662146 TI - Flexible contracts cut costs. AB - Trust managers should look to save money on maternity, sickness and redundancy pay by using more nurses on 'flexible' contracts, the conference heard. PMID- 27662145 TI - Nurses' pay freeze may spark local deals. AB - The nurses' pay Review Body and the Whitley Councils must be 'sidelined' to force trusts to introduce local pay determanation, the human resources director of a London trust urged. PMID- 27662147 TI - ? AB - Performance-related pay Is 'divisive, demoralising, demotivating and unfair', Unison's Deputy Head of Health Malcolm Wing told the conference. Performance related pay schemes are no substitute for good management, he argued, adding that Unison would continue to fight for the retention of the national pay Review Body as local pay would be unfair to nurses. PMID- 27662148 TI - Job evaluation scheme success with staff allowed to opt out. AB - Job evaluation schemes for nurses can be made to work, Jim Norris, deputy personnel director of West Cumbria Health Care NHS Trust, told the conference. PMID- 27662149 TI - Redwood launches back to wards plan for Welsh managers. AB - A call by Welsh Secretary John Redwood for nurse managers to return to clinical practice has been described as admirable by the RCN. But the College has warned that the transfer of nurses from managers' offices back to the wards could be difficult to accomplish. PMID- 27662151 TI - ? AB - Thirst for knowledge: Josephine Cotterell, a National Diary Council nutritionist, and John Wells, Principal of the RCN Institute of Advanced Nursing Education, are pictured at the launch of the Nutrition for Nurses training pack. Packs are available, price L25, from the RCN LANE, 20 Cavendish Square, London W1M OAB. PMID- 27662152 TI - Nurses included in Queen's Birthday Honours List. AB - Among nurses receiving awards in the Queen's Birthday Honours List were. PMID- 27662153 TI - ? AB - Post cards from the edge: The West London Health Promotion Agency has launched a series of post cards highlighting important social Issues such as safe sex. The six cards, drawn by cartoonist Christine Roche, will be on sale in bookstores or can be purchased for L2.50 from the Communication and Design Dept, West London Health Promotion Agency, 1 Armstrong Way, Southall. Middx, UB2 4SA. PMID- 27662154 TI - Reducing families' anxiety in day surgery. AB - A preparation programme for parents and children can reduce their anxiety surrounding day case surgery, Canadian researchers report. PMID- 27662155 TI - Sperm separating techniques do not work. AB - Techniques to sort sperm so that couples can select the sex of their children don't work, according co Australian researchers. PMID- 27662156 TI - Take an aspirin? Have a glass of wine. AB - Much has been written about the health giving properties of drinking wine, and American researchers now suggest a previously overlooked reason. PMID- 27662157 TI - Treating resistant TB and public health. AB - Although treatment of multidrug-resistant TB in HIV positive people is promising, the public health consequences of such treatment must be considered. PMID- 27662158 TI - Mary poppins meets attila the hun. AB - Whether politicians are born or made is a moot point, but Sue Plant certainly showed political promise early on. As a young child she overheard her mother saying of her: Where does she get it from? She never shuts up or lets go of anything.' PMID- 27662159 TI - Phased changes. AB - Since April 6, recipients of a wide variety of social security, sickness and disability benefits have seen changes in their payments. PMID- 27662160 TI - Doh keep committees strictly ethical. AB - How very sad to read so many negative comments about ethics committees from the anonymous author of 'Not strictly ethical' (Viewpoint, June 1). I am a sister on adult intensive care and was elected by my chief nurse six years ago to serve on a well-established and constituted Ethics Review Committee (ERC) at Queen's Medical Centre, Nottingham. PMID- 27662161 TI - Encoded premises: dunces keep out. AB - It is no wonder nursing's claims to be a profession are viewed with amusement when the use of professional language in a professional journal is so disparaged (Jargon jaundice, Viewpoint, June 8). PMID- 27662162 TI - Work? It's just a matter of priorities. AB - What planet is Bruce Fraser on? (Project playtime, No Limits, June 8). He may indeed feel that we Project 2000 students have too much time off but it rather begs the question will he, I Wonder, feel the same when he goes on to rostered service and has to combine a 37.5 hour week with studying for his finals? PMID- 27662163 TI - Respect the elderly care nurses. AB - I was wholeheartedly pleased with the feature 'Elderly care' in the Classified Appointments section (June 8, pages 66-68) and would like to air my own views on the subject. PMID- 27662164 TI - Tea and sympathy goes a long way. AB - I feel compelled to respond to the letter A little less chat on the wards please' from Mrs Antoniah (Letters, June 8). Despite Mrs Antoniah's 'short stint of nursing during the war', I think that perhaps her grasp of the important aspects of nursing, which is a caring career, not just a physical one, has gone awry. PMID- 27662166 TI - Information exchange. PMID- 27662165 TI - ? AB - So Mrs Antoniah was astonished to see nurses on television making beds in apparent slow motion. I am astonished that someone who reads a nursing journal is not aware of the many complex changes which have taken place since the times she describes. PMID- 27662167 TI - Who do they think they are fooling? AB - I was intrigued by Clare Hopkinson's article 'Warm-up exercises: can learning be fun' (Clinical, June 8). What is happening to nurse training? Are we to be subjected to every trendy notion that emanates from the psychobabble culture of America's West Coast? PMID- 27662168 TI - Reunions. AB - The 20-year reunion of the September 1974 class, Victoria Infirmary, Glasgow, is taking place on 10 September. Details from Phyl Bell, 73 Kings wood Road, Bishopton, Renfrewshire PA7 5LG. PMID- 27662169 TI - Do it yourself. AB - Prozject 2000 has wrought many changes in nurse education. One is the transmogrification of schools of nursing into colleges. Another is the merger of those colleges with university departments. One of the current debates doing the rounds in such circles surrounds nurse teachers, who have always had to be qualified teachers, while university lecturers have not. This has led to various discussions of the pros and cons of this situation. PMID- 27662171 TI - Drills, bills and tulip bulbs. AB - Hello there, Health Care Workers! You may remember that I had reservations about the computerisation of my Unit when it was first suggested. Well, you won't be surprised to learn that I was right to be worried! PMID- 27662170 TI - Homes rule. AB - Just over a year ago I was coming to the end of my training as an RGN. I was a late entry to the profession at the age of 45, and had enjoyed almost every minute of the previous three years. I felt pretty glum, both at the prospect of our group dispersing, and the ending of the changes and challenges of life as a student nurse, but mostly at the dismal job prospects. PMID- 27662172 TI - A well kept secret?Nursing Standard's publisher Alison Dunn explains why our recent recruitment marketing campaign caused something of a stir in some quarters. AB - I have been in and around nursing journals for two decades and thought I knew a thing or two about 'the market'. But in giving approval to a marketing campaign to boost Nursing Standard's recruitment advertising recently, I had no inkling of what we were unleashing. PMID- 27662173 TI - Sexuality and Patient Care E van Ooijen Sexuality and Patient Care Charnock Chapman & Hall 224pp L13.99 0-412-47080-2. AB - In their introduction to Sexuality and Patient Care: A Guide for Nurses and Teachers, Els van Ooijen and Andrew Charnock write: 'there is little material available which helps nurses and other health professionals understand the subject in the context of illness and stability.' PMID- 27662174 TI - The Grief Counselling Casebook The Grief Counselling Casebook J Gunzhurg and W Stewart Chapman & Hall 308pp L14.99 0-412-57080-7. AB - The Grief Counselling Casebook: A Student's Guide to Unresolved Grief is in four parts: Introduction and overview; Defining the problem; Exploring context; and Options for the future. PMID- 27662175 TI - Nursing Management, 3rd edition D A Gillies W B Saunders 626pp L21.50 0-7216-6588 8 [Formula: see text]. AB - Nursing Management: A Systems Approach deals with most features of management within nursing. Written at an advanced level, it covers various theoretical perspectives on management including an interesting summary of Japanese. PMID- 27662177 TI - Listings. PMID- 27662176 TI - Reflective practice. AB - Aim and intended learning outcomes The aim of this article is to encourage and enable nurses to develop an understanding of the nature of reflective practice and how this may enhance personal and professional learning. After reading this article, the nurse should be able to. PMID- 27662178 TI - Tracking weight change, insulin resistance, stress, and aerobic fitness over 4 years of college. AB - OBJECTIVE: To determine if weight gain is accompanied by development of insulin resistance (IR) during 4 years in college. PARTICIPANTS: Two cohorts of college students were enrolled in fall semesters 2009 and 2010 and tracked for 4 years. METHODS: Following a 12-hour fast, subjects reported for measurement of body mass index (BMI), perceived stress (PSS), aerobic fitness, and blood glucose, insulin, and lipids. RESULTS: In the first year, 33% of subjects were overweight or obese, and 20% were hyperinsulinemic. Year 4 had 29 remaining subjects with disproportionate attrition of overweight and obese individuals. Just over half the subjects gained weight (WI), whereas nearly 30% lost considerable amounts (WD). WD showed significant decline in fasting insulin, low-density lipoprotein (LDL) cholesterol, and PSS from year 1. WI was primarily highly fit men who did not demonstrate increased IR. CONCLUSION: WI was not associated with IR over 4 years of college. PMID- 27662179 TI - Reentrant phenomenon and inverse magnetocaloric effect in a generalized spin (1/2, s) Fisher's super-exchange antiferromagnet. AB - The thermodynamic and magnetocaloric properties of a generalized spin-(1/2, s) Fisher's super-exchange antiferromagnet are investigated precisely by using the decoration-iteration mapping transformation. Besides the critical temperature, sublattice magnetization, total magnetization, entropy and specific heat, the isothermal entropy change and adiabatic temperature change are also rigorously calculated in order to examine the cooling efficiency of the model in the vicinity of the first- and second-order phase transitions. It is shown that an enhanced inverse magnetocaloric effect occurs around the temperature interval [Formula: see text] for any magnetic-field change [Formula: see text]. The most pronounced inverse magnetocaloric effect can be found nearby the critical field, which corresponds to the zero-temperature phase transition from the long-range ordered ground state to the paramagnetic one. The observed phenomenon increases with an increasing value of decorating spins. Furthermore, sufficiently high values of decorating spins have also been linked to the possibility of observing reentrant phase transitions at finite temperatures. PMID- 27662180 TI - Novel Signs and Their Clinical Utility in Diagnosing Complex Regional Pain Syndrome (CRPS): A Prospective Observational Cohort Study. AB - OBJECTIVES: Delays in diagnosis occur with complex regional pain syndrome (CRPS). We define and prospectively demonstrate that novel bedside tests measuring body perception disruption can identify patients with CRPS postfracture. METHODS: The objectives of our study were to define and validate 4 bedside tests, to identify the prevalence of positive tests in patients with CRPS and other chronic pain conditions, and to assess the clinical utility (sensitivity, specificity, positive predictive value, negative predictive value) for identifying CRPS within a Fracture cohort. This was a single UK teaching hospital prospective cohort study with 313 recruits from pain-free volunteers and patients with chronic pain conditions.Four novel tests were Finger Perception (FP), Hand Laterality identification (HL), Astereognosis (AS), and Body Scheme (BS) report. Five questionnaires (Brief Pain Inventory, Upper Extremity Functional Index, Lower Extremity Functional Index, Neglect-like Symptom Questionnaire, Hospital Anxiety and Depression Score) assessed the multidimensional pain experience. RESULTS: FP and BS were the best performing tests. Prospective monitoring of fracture patients showed that out of 7 fracture patients (total n=47) who had both finger misperception and abnormal BS report at initial testing, 3 developed persistent pain with 1 having a formal diagnosis of CRPS. DISCUSSION: Novel signs are reliable, easy to perform, and present in chronic pain patients. FP and BS have significant clinical utility in predicting persistent pain in a fracture group thereby allowing targeted early intervention. PMID- 27662182 TI - Spiritual/Religious Beliefs & Medication Adherence in Black Women with Hypertension. AB - Black women have the highest rate of hypertension (HTN) in the U.S. and perhaps the world. Because they are deemed the most religiously devout group in the U.S., it is plausible that faithfulness to spiritual/religious practices may yield more adherence to HTN medication regimens. This study examined spiritual/religious beliefs in relation to antihypertensive medication adherence in Black women with HTN. Although results showed no association between beliefs and adherence, women who developed trusting relationships with their healthcare provider were more likely to be adherent to their medications. PMID- 27662181 TI - Enhancing Virtual Screening Performance of Protein Kinases with Molecular Dynamics Simulations. AB - In silico virtual screening (VS) is a powerful hit identification technique used in drug discovery projects that aims to effectively distinguish true actives from inactive or decoy molecules. To better capture the dynamic behavior of protein drug targets, compound databases may be screened against an ensemble of protein conformations, which may be experimentally determined or generated computationally, i.e. via molecular dynamics (MD) simulations. Several studies have shown that conformations generated by MD are useful in identifying novel hit compounds, in part because structural rearrangements sampled during MD can provide novel targetable areas. However, it remains difficult to predict a priori when an MD conformation will outperform a VS against the crystal structure alone. Here, we assess whether MD conformations result in improved VS performance for six protein kinases. MD conformations are selected using three different methods, and their VS performances are compared to the corresponding crystal structures. Additionally, these conformations are used to train ensembles, and their VS performance is compared to the individual MD conformations and the corresponding crystal structures using receiver operating characteristic curve (ROC) metrics. We show that performing MD results in at least one conformation that offers better VS performance than the crystal structure, and that, while it is possible to train ensembles to outperform the crystal structure alone, the extent of this enhancement is target dependent. Lastly, we show that the optimal structural selection method is also target dependent and recommend optimizing virtual screens on a kinase-by-kinase basis to improve the likelihood of success. PMID- 27662184 TI - Concave Platinum-Copper Octopod Nanoframes Bounded with Multiple High-Index Facets for Efficient Electrooxidation Catalysis. AB - Multimetallic nanoframes with three-dimensional (3D) catalytic surfaces represent an emerging class of efficient nanocatalysts. However, it still remains a challenge in engineering nanoframes via simple and economical methods. Herein, we report a facile one-pot synthetic strategy to synthesize Pt-Cu nanoframes bounded with multiple high-index facets as highly active electrooxidation catalysts. Two distinct octopod nanoframes, namely, concave PtCu2 octopod nanoframes (PtCu2 CONFs) and ultrathin PtCu octopod nanoframes (PtCu UONFs) were successfully synthesized by simply changing the feeding Pt and Cu precursors. Interestingly, the PtCu2 CONFs are constructed by eight symmetric feet with sharp tips, which are enclosed by high-index facets of n (111)-(111), such as {553}, {331}, and {221}. Benefiting from their 3D accessible surfaces and multiple high-index facets, the self-supported PtCu2 CONFs catalysts exhibit excellent electrocatalytic performance and superior CO-tolerant ability. For methanol oxidation reaction, the PtCu2 CONFs catalysts exhibit more than 7-fold increase in activities, 205 mV lower in the onset potential compared with commercial Pt/C. More importantly, when facing harsh electrochemical reaction conditions, the PtCu2 CONFs are well-preserved in the catalytic activities, architectural features, and stepped surfaces. The PtCu UONFs with 12 ultrathin edges, however, suffer from breakdown. The present work provides guidelines for the rational design and synthesis of nanoframe catalysts with both high activity and stability. PMID- 27662183 TI - Neo High-Density Lipoprotein Produced by the Streptococcal Serum Opacity Factor Activity against Human High-Density Lipoproteins Is Hepatically Removed via Dual Mechanisms. AB - Injection of streptococcal serum opacity factor (SOF) into mice reduces the plasma cholesterol level by ~40%. In vitro, SOF converts high-density lipoproteins (HDLs) into multiple products, including a small HDL, neo HDL. In vitro, neo HDL accounts for ~60% of the protein mass of the SOF reaction products; in vivo, the accumulated mass of neo HDL is <1% of that observed in vitro. To identify the underlying cause of this difference, we determined the fate of neo HDL in plasma in vitro and in vivo. Following incubation with HDL, neo HDL-PC rapidly transfers to HDL, giving a small remnant, which fuses with HDL. An increased level of SR-B1 expression in Huh7 hepatoma cells and a reduced level of LDLR expression in CHO cells had little effect on neo HDL-[3H]CE uptake. Thus, the dominant receptors for neo HDL uptake are not LDLR or SR-B1. The in vivo metabolic fates of neo HDL-[3H]CE and HDL-[3H]CE were different. Thirty minutes after the injection of neo HDL-[3H]CE and HDL-[3H]CE into mice, plasma [3H]CE counts were 40 and 53%, respectively, of injected counts, with 10 times more [3H]CE appearing in the livers of neo HDL-[3H]CE-injected than in those of HDL-[3H]CE-injected mice. These data support a model of neo HDL-[3H]CE clearance by two parallel pathways. At early post-neo HDL-[3H]CE injection times, some neo HDL is directly removed by the liver; the remainder transfers its PC to HDL, leaving a remnant that fuses with HDL, which is also hepatically removed more slowly. Given that SR-B1 and SOF both remove CE from HDL, this novel mechanism may also underlie the metabolism of remnants released by hepatocytes following selective SR-B1-mediated uptake of HDL-CE. PMID- 27662185 TI - Cytofkit: A Bioconductor Package for an Integrated Mass Cytometry Data Analysis Pipeline. AB - Single-cell mass cytometry significantly increases the dimensionality of cytometry analysis as compared to fluorescence flow cytometry, providing unprecedented resolution of cellular diversity in tissues. However, analysis and interpretation of these high-dimensional data poses a significant technical challenge. Here, we present cytofkit, a new Bioconductor package, which integrates both state-of-the-art bioinformatics methods and in-house novel algorithms to offer a comprehensive toolset for mass cytometry data analysis. Cytofkit provides functions for data pre-processing, data visualization through linear or non-linear dimensionality reduction, automatic identification of cell subsets, and inference of the relatedness between cell subsets. This pipeline also provides a graphical user interface (GUI) for ease of use, as well as a shiny application (APP) for interactive visualization of cell subpopulations and progression profiles of key markers. Applied to a CD14-CD19- PBMCs dataset, cytofkit accurately identified different subsets of lymphocytes; applied to a human CD4+ T cell dataset, cytofkit uncovered multiple subtypes of TFH cells spanning blood and tonsils. Cytofkit is implemented in R, licensed under the Artistic license 2.0, and freely available from the Bioconductor website, https://bioconductor.org/packages/cytofkit/. Cytofkit is also applicable for flow cytometry data analysis. PMID- 27662187 TI - Obesity and ECG left ventricular hypertrophy. AB - AIM: Our aim was to investigate the prevalence and the prognostic significance for fatal and nonfatal cerebrovascular and cardiovascular events of different ECG criteria for left ventricular hypertrophy (LVH) in normal weight, overweight and obese patients in an adult Italian population. METHODS: A total of 18 330 adults (mean age 54 +/- 11 years, 55% women, 53% hypertensive patients) were analyzed from the Moli-sani cohort. Obesity was defined using the ATPIII criteria. ECG-LVH was defined according to 2013 ESC-ESH guidelines. RESULTS: The age and sex adjusted prevalence of ECG-LVH did not differ from normal weight patients to class 1-3 obesity patients, when Cornell-voltage criterion was used. In overweight and obese patients, as compared with normal weight patients, a progressively lower prevalence of ECG-LVH was observed when the Sokolow-Lyon index was used, whereas a higher prevalence was shown by using the aVL R-wave voltage (>11 and >5.7 mm) and the Cornell-voltage-QRS duration product. The incidence of cardiovascular events was significantly greater in patients with ECG LVH diagnosis by the Cornell voltage [hazard ratio 1.89, 95% confidence interval (CI) 1.05-3.39] and the Cornell product (hazard ratio 1.87, 95% CI 1.31-2.67). After adjusting for different confounders (age, sex, cigarette, hypertension, hypercholesterolemia, diabetes, income, education, occupational class and physical activity) and for BMI categories, only the Cornell product remained significantly associated with a higher incidence of cardiovascular events (hazard ratio 1.66; 95% CI 1.16-2.38). The predictive significance of different LVH criteria was assessed across BMI categories; after adjusting for confounders, no LVH criteria were significantly associated with an increased risk of cardiovascular events in obese patients; Cornell-product LVH remained an independent predictor of events in normal weight and overweight individuals (hazard ratio 2.63; 95% CI 1.10-6.28 and hazard ratio 2.72; 95% CI 1.52-4.25, respectively). CONCLUSION: Our results confirm that ECG LVH prevalence may differ according to the criteria used across BMI categories in a low cardiovascular risk cohort. The use of different LVH criteria according to BMI categories may improve cardiovascular risk stratification in a general population independently of several confounding factors. PMID- 27662186 TI - Heat Transfer Behavior across the Dentino-Enamel Junction in the Human Tooth. AB - During eating, the teeth usually endure the sharply temperature changes because of different foods. It is of importance to investigate the heat transfer and heat dissipation behavior of the dentino-enamel junction (DEJ) of human tooth since dentine and enamel have different thermophysical properties. The spatial and temporal temperature distributions on the enamel, dentine, and pulpal chamber of both the human tooth and its discontinuous boundaries, were measured using infrared thermography using a stepped temperature increase on the outer boundary of enamel crowns. The thermal diffusivities for enamel and dentine were deduced from the time dependent temperature change at the enamel and dentine layers. The thermal conductivities for enamel and dentine were calculated to be 0.81 Wm-1K-1 and 0.48 Wm-1K-1 respectively. The observed temperature discontinuities across the interfaces between enamel, dentine and pulp-chamber layers were due to the difference of thermal conductivities at interfaces rather than to the phase transformation. The temperature gradient distributes continuously across the enamel and dentine layers and their junction below a temperature of 42 degrees C, whilst a negative thermal resistance is observed at interfaces above 42 degrees C. These results suggest that the microstructure of the dentin-enamel junction (DEJ) junction play an important role in tooth heat transfer and protects the pulp from heat damage. PMID- 27662188 TI - Anthropometric measures change and incidence of high blood pressure levels among adults: a population-based prospective study in Southern Brazil. AB - OBJECTIVE: The objective was to evaluate the effects of BMI and waist circumference change on the cumulative incidence of high blood pressure levels (HBP) among adults. METHODS: Prospective longitudinal study in Southern Brazil, with a sample evaluated in 2009 (n = 1720) and 2012 (n = 1213). The incidence of HBP was estimated using measured values of systolic and diastolic arterial pressure (>=140/90 mmHg). RESULTS: The prevalence of overweight (BMI >= 25 kg/m) was 47.3% in 2009 and 55.0% in 2012. The incidence of HBP was 32.0%. Being overweight or having an elevated waist circumference (top quartile) in the two waves increased the incidence of HBP [odds ratio 3.41 (95% confidence interval (CI) 2.10; 5.53) and 5.42 (95% CI 2.65; 11.08), respectively] compared with those always eutrophic. Being overweight in either wave also increased the risk of HBP, whereas reducing waist circumference was a protective factor. When the annual BMI and waist circumference change were evaluated (conditional to the baseline measurements, age, and sex) the adjusted predicted incidence of HBP was 46.5% (95% CI 36.9; 56.1) among individuals with an annual BMI change more than +1.0 kg/m, and 45.1% (95% CI 36.7; 53.4) among those with an annual waist circumference change more than +3.0 cm. Among those who reduced their BMI and waist circumference, the incidence of HBP were 25.9 and 23.8%, respectively. CONCLUSION: Being overweight (in any wave), maintaining an elevated waist circumference, or having an annual rise of these measurements above the expected values, all increased the incidence of HBP. Reducing the waist circumference showed greater benefits for the prevention of HBP than BMI changes. PMID- 27662189 TI - Social disparities explain differences in hypertension prevalence, detection and control in Colombia. AB - OBJECTIVE: Hypertension is the principal risk factor for cardiovascular diseases. The global Prospective Urban Rural Epidemiology study showed that the levels of awareness, treatment and control of this condition are very low worldwide and show large regional variations related to a country's income index. The aim of the present analysis was to identify associations between sociodemographic, geographic, anthropometric, behavioral and clinical factors and the awareness, treatment and control of hypertension within Colombia - a high-middle income country which participated in the global Prospective Urban Rural Epidemiology study. METHODS AND RESULTS: The sample comprised 7485 individuals aged 35-70 years (mean age 50.8 years, 64% women). Mean SBP and DBP were 129.12 +/- 21.23 and 80.39 +/- 11.81 mmHg, respectively. The overall prevalence of hypertension was 37.5% and was substantially higher amongst participants with the lowest educational level, who had a 25% higher prevalence (<0.001). Hypertension awareness, treatment amongst those aware, and control amongst those treated were 51.9, 77.5 and 37.1%, respectively. The prevalence of hypertension was higher amongst those with a higher BMI (<0.001) or larger waist-hip ratio (<0.001). Being male, younger, a rural resident and having a low level of education was associated with significantly lower hypertension awareness, treatment and control. The use of combination therapy was very low (27.5%) and was significantly lower in rural areas and amongst those with a low income. CONCLUSION: Overall Colombia has a high prevalence of hypertension in combination with very low levels of awareness, treatment and control; however, we found large variations within the country that appear to be associated with sociodemographic disparities. PMID- 27662190 TI - Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies. AB - INTRODUCTION: Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects. MATERIALS AND METHODS: 3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA ProfilerTM system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics. RESULTS: Of the 3,000 subjects, 2,995 (99.83%) were analysable for body fat, 2,828 (94.27%) were analysable when body fat and one thigh was included, and 2,775 (92.50%) were fully analysable for body fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view. DISCUSSION AND CONCLUSIONS: In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success rate for body composition analysis. This research has been conducted using the UK Biobank Resource. PMID- 27662191 TI - Transcriptome Sequencing Analysis and Functional Identification of Sex Differentiation Genes from the Mosquito Parasitic Nematode, Romanomermis wuchangensis. AB - Mosquito-transmitted diseases like malaria and dengue fever are global problem and an estimated 50-100 million of dengue or dengue hemorrhagic fever cases are reported worldwide every year. The mermithid nematode Romanomermis wuchangensis has been successfully used as an ecosystem-friendly biocontrol agent for mosquito prevention in laboratory studies. However, this nematode can not undergo sex differentiation in vitro culture, which has seriously affected their application of biocontrol in the field. In this study, based on transcriptome sequencing analysis of R. wuchangensis, Rwucmab-3, Rwuclaf-1 and Rwuctra-2 were cloned and used to investigate molecular regulatory function of sex differentiation. qRT-PCR results demonstrated that the expression level of Rwucmab-3 between male and female displayed obvious difference on the 3rd day of parasitic stage, which was earlier than Rwuclaf-1 and Rwuctra-2, highlighting sex differentiation process may start on the 3rd day of parasitic stage. Besides, FITC was used as a marker to test dsRNA uptake efficiency of R. wuchangensis, which fluorescence intensity increased with FITC concentration after 16 h incubation, indicating this nematode can successfully ingest soaking solution via its cuticle. RNAi results revealed the sex ratio of R. wuchangensis from RNAi treated groups soaked in dsRNA of Rwucmab-3 was significantly higher than gfp dsRNA treated groups and control groups, highlighting RNAi of Rwumab-3 may hinder the development of male nematodes. These results suggest that Rwucmab-3 mainly involves in the initiation of sex differentiation and the development of male sexual dimorphism. Rwuclaf-1 and Rwuctra-2 may play vital role in nematode reproductive and developmental system. In conclusion, transcript sequences presented in this study could provide more bioinformatics resources for future studies on gene cloning and other molecular regulatory mechanism in R. wuchangensis. Moreover, identification and functional analysis of sex differentiation genes may clarify the sex differentiation mechanism of R. wuchangensis, which are helpful to solve the uncompleted sex differentiation problem in vitro culture and the potential large scale field application controlling the larvae of C. quinquefasciatus, A. aegypti and A. albopictus. PMID- 27662192 TI - Micro and Macroscale Drivers of Nutrient Concentrations in Urban Streams in South, Central and North America. AB - Global metrics of land cover and land use provide a fundamental basis to examine the spatial variability of human-induced impacts on freshwater ecosystems. However, microscale processes and site specific conditions related to bank vegetation, pollution sources, adjacent land use and water uses can have important influences on ecosystem conditions, in particular in smaller tributary rivers. Compared to larger order rivers, these low-order streams and rivers are more numerous, yet often under-monitored. The present study explored the relationship of nutrient concentrations in 150 streams in 57 hydrological basins in South, Central and North America (Buenos Aires, Curitiba, Sao Paulo, Rio de Janeiro, Mexico City and Vancouver) with macroscale information available from global datasets and microscale data acquired by trained citizen scientists. Average sub-basin phosphate (P-PO4) concentrations were found to be well correlated with sub-basin attributes on both macro and microscales, while the relationships between sub-basin attributes and nitrate (N-NO3) concentrations were limited. A phosphate threshold for eutrophic conditions (>0.1 mg L-1 P-PO4) was exceeded in basins where microscale point source discharge points (eg. residential, industrial, urban/road) were identified in more than 86% of stream reaches monitored by citizen scientists. The presence of bankside vegetation covaried (rho = -0.53) with lower phosphate concentrations in the ecosystems studied. Macroscale information on nutrient loading allowed for a strong separation between basins with and without eutrophic conditions. Most importantly, the combination of macroscale and microscale information acquired increased our ability to explain sub-basin variability of P-PO4 concentrations. The identification of microscale point sources and bank vegetation conditions by citizen scientists provided important information that local authorities could use to improve their management of lower order river ecosystems. PMID- 27662195 TI - You're the Flight Surgeon. AB - Nelms JM. You're the flight surgeon: probable Herpes zoster. Aerosp Med Hum Perform. 2015; 86(8):754-756. PMID- 27662194 TI - The Patterning Cascade Model and Carabelli's trait expression in metameres of the mixed human dentition: exploring a morphogenetic model. AB - OBJECTIVES: The Patterning Cascade Model (PCM) provides an evolutionary developmental framework for exploring diversity in tooth crown form. According to the model, proximity of secondary enamel knots and tooth germ size track underlying developmental processes that dictate ultimate crown morphology (i.e., cusp number, accessory cusp presence/size). Previous research has shown the model to successfully predict variation in Carabelli's trait expression between antimeric and metameric pairs of human permanent molars. In this study, we quantify Carabelli's trait expression for metameres of the mixed dentition (dm2 and M1) and assess the PCM's potential for explaining differences in expression between the two elements. MATERIALS AND METHODS: Crown dimensions, intercusp distances, and Carabelli's trait expression were collected from 49 subadults possessing observable dm2/M1 pairs. Wilcoxon signed-rank tests and paired t-tests were performed to assess whether metameres differ significantly in morphometric variables. We explored the relationships between relative intercusp distances (RICDs) and Carabelli's trait expression using proportional odds logistic regression. RESULTS: Intra-individual dm2/M1 pairs differed significantly in Carabelli's trait expression (p = 0.01), with dm2 exhibiting higher grades of expression more commonly despite its smaller crown size. Paired molars differed in only one statistically significant RICD: metacone-hypocone (p < 0.01). Most RICDs shared the predicted negative relationship with Carabelli's trait expression, but this relationship was only statistically significant for three RICDs in the dm2 (mean, protocone-paracone, metacone-hypocone). CONCLUSIONS: We found mixed support for the PCM's ability to explain differences in Carabelli's trait expression between metameres of the mixed molar row. Results suggest that protocone-paracone enamel knot spacing has the greatest influence on Carabelli's trait expression. Lack of statistical significance for many of the relationships explored may reflect limitations related to sample composition and sample size. PMID- 27662196 TI - You're the Flight Surgeon. AB - Duong A. You're the flight surgeon: arrythmogenic right ventricular cardiomyopathy. Aerosp Med Hum Perform. 2015; 86(8):756-759. PMID- 27662197 TI - Comparative Evaluation of the Ostium After External and Nonendoscopic Endonasal Dacryocystorhinostomy Using Image Processing (Matlabs and Image J) Softwares. AB - PURPOSE: The purpose of this study was to compare the characteristics of the ostium after external dacryocystorhinostomy and nonendoscopic endonasal dacryocystorhinostomy (NEN-DCR). METHODS: This cross-sectional study included patients who underwent a successful external dacryocystorhinostomy or NEN-DCR and had >=1 month follow up. Pictures of the ostium were captured with a nasal endoscope (4 mm, 30 degrees ) after inserting a lacrimal probe premarked at 2 mm. Image analyses were performed using Image J and Contour softwares. RESULTS: Of the 113 patients included, external dacryocystorhinostomy group had 53 patients and NEN-DCR group had 60 patients. The mean age of patients in the NEN-DCR group (38 years) was significantly (p < 0.05) lower than the external dacryocystorhinostomy group (50 years). There was no statistically significant difference (2 sample t test, p > 0.05) in mean follow up (6 vs. 4 months), maximum diameter of ostium (8 vs. 7 mm), perpendicular drawn to it (4 vs. 4 mm), area of ostium (43 vs. 36 mm), and the minimum distance between common internal punctum and edge of the ostium (1 vs. 1 mm) between the external and NEN-DCR groups. CONCLUSIONS: Image processing softwares offer simple and objective method to measure the ostium. While ostia are comparable in size, their relative position differs with posteriorly placed ostia in external compared with inferior in NEN-DCR. PMID- 27662193 TI - Overexpression of Glutamate Decarboxylase in Mesenchymal Stem Cells Enhances Their Immunosuppressive Properties and Increases GABA and Nitric Oxide Levels. AB - The neurotransmitter GABA has been recently identified as a potent immunosuppressive agent that targets both innate and adaptive immune systems and prevents disease progression of several autoimmunity models. Mesenchymal stem cells (MSCs) are self-renewing progenitor cells that differentiate into various cell types under specific conditions, including neurons. In addition, MSC possess strong immunosuppressive capabilities. Upon cytokine priming, undifferentiated MSC suppress T-cell proliferation via cell-to-cell contact mechanisms and the secretion of soluble factors like nitric oxide, prostaglandin E2 and IDO. Although MSC and MSC-derived neuron-like cells express some GABAergic markers in vitro, the role for GABAergic signaling in MSC-mediated immunosuppression remains completely unexplored. Here, we demonstrate that pro-inflammatory cytokines selectively regulate GAD-67 expression in murine bone marrow-MSC. However, expression of GAD-65 is required for maximal GABA release by MSC. Gain of function experiments using GAD-67 and GAD-65 co-expression demonstrates that GAD increases immunosuppressive function in the absence of pro-inflammatory licensing. Moreover, GAD expression in MSC evokes an increase in both GABA and NO levels in the supernatants of co-cultured MSC with activated splenocytes. Notably, the increase in NO levels by GAD expression was not observed in cultures of isolated MSC expressing GAD, suggesting crosstalk between these two pathways in the setting of immunosuppression. These results indicate that GAD expression increases MSC-mediated immunosuppression via secretion of immunosuppressive agents. Our findings may help reconsider GABAergic activation in MSC for immunological disorders. PMID- 27662198 TI - Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa. AB - Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings. PMID- 27662199 TI - Amyloid Pseudo-Dacryolith and Nasolacrimal Obstruction in a 67-Year-Old Male. AB - A 67-year-old male with a 35-year history of left-sided epiphora presented with a nonpainful, noninflamed, left medial canthal mass and complete left nasolacrimal obstruction. During routine dacryocystorhinostomy, a lesion was present within the lacrimal sac that mimicked a lacrimal stone in appearance but with a consistency concerning for malignancy. Histologically, the lesion displayed apple green birefringence on polarized light microscopy and Congo red staining. The patient was referred to the hematology service for evaluation, which failed to reveal systemic disease. There is 1 previous report of localized amyloidosis to the nasolacrimal excretory system in which the lesion was invasive and caused bony erosion. The authors present a second case of localized, nasolacrimal amyloidosis mimicking both neoplasm and dacryolith without bony erosion. PMID- 27662200 TI - Solution Structure of the Cuz1 AN1 Zinc Finger Domain: An Exposed LDFLP Motif Defines a Subfamily of AN1 Proteins. AB - Zinc binding domains are common and versatile protein structural motifs that mediate diverse cellular functions. Among the many structurally distinct families of zinc finger (ZnF) proteins, the AN1 domain remains poorly characterized. Cuz1 is one of two AN1 ZnF proteins in the yeast S. cerevisiae, and is a stress inducible protein that functions in protein degradation through direct interaction with the proteasome and Cdc48. Here we report the solution structure of the Cuz1 AN1 ZnF which reveals a compact C6H2 zinc-coordinating domain that resembles a two-finger hand holding a tri-helical clamp. A central phenylalanine residue sits between the two zinc-coordinating centers. The position of this phenylalanine, just before the penultimate zinc-chelating cysteine, is strongly conserved from yeast to man. This phenylalanine shows an exceptionally slow ring flipping rate which likely contributes to the high rigidity and stability of the AN1 domain. In addition to the zinc-chelating residues, sequence analysis of Cuz1 indicates a second highly evolutionarily conserved motif. This LDFLP motif is shared with three human proteins-Zfand1, AIRAP, and AIRAP-L-the latter two of which share similar cellular functions with Cuz1. The LDFLP motif, while embedded within the zinc finger domain, is surface exposed, largely uninvolved in zinc chelation, and not required for the overall fold of the domain. The LDFLP motif was dispensable for Cuz1's major known functions, proteasome- and Cdc48-binding. These results provide the first structural characterization of the AN1 zinc finger domain, and suggest that the LDFLP motif may define a sub-family of evolutionarily conserved AN1 zinc finger proteins. PMID- 27662201 TI - Number and type of TET2 mutations in chronic myelomonocytic leukemia and their clinical relevance. PMID- 27662203 TI - Amyloid cast tubulopathy: a unique form of immunoglobulin-induced renal disease. PMID- 27662202 TI - Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia. AB - We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20 27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data. PMID- 27662204 TI - Differential expression, localization and activity of MARCKS between mantle cell lymphoma and chronic lymphocytic leukemia. PMID- 27662205 TI - Bone marrow stromal cells show distinct gene expression patterns depending on symptomatically involved organs in multiple myeloma. PMID- 27662206 TI - Metal Dissipation and Inefficient Recycling Intensify Climate Forcing. AB - In the metals industry, recycling is commonly included among the most viable options for climate change mitigation, because using secondary (recycled) instead of primary sources in metal production carries both the potential for significant energy savings and for greenhouse gas emissions reduction. Secondary metal production is, however, limited by the relative quantity of scrap available at end-of-life for two reasons: long product lifespans during use delay the availability of the material for reuse and recycling; and end-of-life recycling rates are low, a result of inefficient collection, separation, and processing. For a few metals, additional losses exist in the form of in-use dissipation. The sum of these lost material flows forms the theoretical maximum potential for future efficiency improvements. Based on a dynamic material flow analysis, we have evaluated these factors from an energy perspective for 50 metals and calculated the corresponding greenhouse gas emissions associated with the supply of lost material from primary sources that would otherwise be used to satisfy demand. A use-by-use examination demonstrates the potential emission gains associated with major application sectors. The results show that minimizing in use dissipation and constraints to metal recycling have the potential to reduce greenhouse gas emissions from the metal industry by about 13-23%, corresponding to 1% of global anthropogenic greenhouse gas emissions. PMID- 27662207 TI - Recent developments in epigenetics of pediatric asthma. AB - PURPOSE OF REVIEW: The goal of this review was to systematically analyze recent studies updating our knowledge on the role of epigenetic mechanisms in childhood asthma. RECENT FINDINGS: A systematic literature search was conducted that identified 23 fresh articles published within the last 5 years reporting the results of human studies on the relationships between epigenetic modifications and childhood asthma or its/related phenotypes. In almost all these studies, meaningful associations between levels of epigenetic marks (DNA methylation and/or histone modifications) and pediatric asthma or its/related phenotypes have been observed. In addition, many studies identified by our screening analyzed those associations in the context of environmental factors, such as pollution, tobacco smoke, farming, or diet, showing in a huge majority a modifying effect of those exposures. SUMMARY: The results of our systematic literature search provide a strong support for the role of epigenetic mechanisms in (mediating the effects of environmental exposure on) pediatric asthma. This knowledge may possibly be translated into diagnostic and/or therapeutic approaches. PMID- 27662208 TI - Growth parameters: the cheap and easy genetic test. PMID- 27662209 TI - Developmental behavioral neurology: an update. PMID- 27662211 TI - Cellular Functions and Gene and Protein Expression Profiles in Endothelial Cells Derived from Moyamoya Disease-Specific iPS Cells. AB - BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a slow, progressive steno occlusive disease, arising in the terminal portions of the cerebral internal carotid artery. However, the functions and characteristics of the endothelial cells (ECs) in MMD are unknown. We analyzed these features using induced pluripotent stem cell (iPSC)-derived ECs. METHODS: iPSC lines were established from the peripheral blood of three patients with MMD carrying the variant RNF213 R4810K, and three healthy persons used as controls. After the endothelial differentiation of iPSCs, CD31+CD144+ cells were purified as ECs using a cell sorter. We analyzed their proliferation, angiogenesis, and responses to some angiogenic factors, namely VEGF, bFGF, TGF-beta, and BMP4. The ECs were also analyzed using DNA microarray and proteomics to perform comprehensive gene and protein expression analysis. RESULTS: Angiogenesis was significantly impaired in MMD regardless of the presence of any angiogenic factor. On the contrary, endothelial proliferation was not significant between control- and MMD-derived cells. Regarding DNA microarray, pathway analysis illustrated that extracellular matrix (ECM) receptor-related genes, including integrin beta3, were significantly downregulated in MMD. Proteomic analysis revealed that cytoskeleton-related proteins were downregulated and splicing regulation-related proteins were upregulated in MMD. CONCLUSIONS: Downregulation of ECM receptor-related genes may be associated with impaired angiogenic activity in ECs derived from iPSCs from patients with MMD. Upregulation of splicing regulation-related proteins implied differences in splicing patterns between control and MMD ECs. PMID- 27662210 TI - IL6-174 G>C Polymorphism (rs1800795) Association with Late Effects of Low Dose Radiation Exposure in the Portuguese Tinea Capitis Cohort. AB - Head and neck cancers, and cardiovascular disease have been described as late effects of low dose radiation (LDR) exposure, namely in tinea capitis cohorts. In addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to LDR late effects. The -174 G>C (rs1800795) SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial. We assessed the association of the IL6-174 G>C SNP with LDR effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The IL6-174 G>C SNP was genotyped in 1269 individuals formerly irradiated for tinea capitis. This sampling group included thyroid cancer (n = 36), basal cell carcinoma (n = 113) and cases without thyroid or basal cell carcinoma (1120). A subgroup was assessed for atherosclerosis by ultrasonography (n = 379) and included matched controls (n = 222). Genotypes were discriminated by real time PCR using a TaqMan SNP genotyping assay. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk, both in the genotypic (OR = 3.57, CI = 1.60-7.95, p-value = 0.002) and in the recessive (OR = 3.02, CI = 1.42-6.42, p-value = 0.004) models. Irradiation alone was not a risk factor for carotid atherosclerosis. We did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk. The IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the LDR context. PMID- 27662213 TI - Scams and Scoundrels. PMID- 27662212 TI - Comprehensive influence of environmental factors on the emission rate of formaldehyde and VOCs in building materials: Correlation development and exposure assessment. AB - Temperature and relative humidity can simultaneously change in indoor environment, which significantly affect the emission rate of formaldehyde and volatile organic compounds (VOCs) from building materials. Prior studies generally focus on the single effect of temperature or relative humidity, and the combined effect is not considered. This paper investigates the comprehensive influence of temperature and relative humidity on the emission rate of pollutants from building materials. Correlation between the emission rate and the combined environmental factors is derived theoretically. Data in literature are applied to validate the effectiveness of the correlation. With the correlation, the indoor formaldehyde concentration in summer is predicted to be 1.63 times of that in winter in Beijing, which is approximately consistent with surveyed data. In addition, a novel approach is proposed to assess the human health impact due to pollutants emitted from building materials at varied temperature and relative humidity. An association between the human carcinogenic potential (HCP) and the environmental factors is obtained. By introducing a reference room model developed previously, it is calculated that the HCP of bedroom at high relative humidity (70%, 25 degrees C) for formaldehyde exceeds 10-4 cases, meaning high cancer health risk. This study should prove useful for evaluating the emission behaviors and the associated exposure of pollutants from building materials at varied environmental conditions. PMID- 27662214 TI - Our Senior Editorial Reviewers: A Centerpiece. PMID- 27662215 TI - Idiopathic adrenal hematoma mimicking neoplasia: A case report. AB - INTRODUCTION: Adrenal haemorrhage is a relatively rare condition. If there is not a specific ethology describing adrenal hematoma, then, this is termed as 'idiopathic adrenal hematoma'. PRESENTATION OF CASE: We presented a case of idiopathic adrenal hematoma in this study. A 62-year-old woman was referred to our hospital for evaluation of a 40mm mass in the left upper abdominal cavity. The histopathological findings of the surgical specimen revealed a hematoma with normal adrenal tissue. DISCUSSION: The incidence of adrenal haemorrhage was found to be 1.1% regarding autopsy results. The Adrenal gland is highly vascular and vulnerable to haemorrhage. Before a surgical operation, it is difficult to diagnose idiopathic adrenal hematomas. CONCLUSION: An adrenal hematoma should be kept in mind when adrenal masses assessing. PMID- 27662216 TI - Acute appendiceal abscess and atraumatic splenic rupture: A case of dual pathology. AB - INTRODUCTION: Atraumatic splenic rupture is a rare surgical emergency that is often attributed to neoplastic or infectious causes. Rarely, it has been identified to also occur in the setting of an acute severe sepsis and in cases of pelvic or splenic abscess formation post-appendicectomy. However, to our knowledge, the co-presentation of acute appendiceal abscess and splenic rupture has not been previously described. PRESENTATION OF CASE: We present the case of a 67-year old male with decompensating haemorrhagic shock secondary to atraumatic splenic rupture on a background of an inadequately treated complicated appendicitis originally managed as diverticulitis with antibiotics in the community. Intra-operatively, in addition to a de-gloved, ruptured spleen; an acutely inflamed appendiceal abscess was also identified. A concomitant splenectomy, washout and appendicectomy and was therefore performed. Histopathological examination revealed a normal spleen with a stripped capsular layer. Mucosal ulceration, transmural inflammation and serositis of the appendix appeared to be consistent with acute appendicitis. DISCUSSION: Our case demonstrates how inadequately treated sepsis may predispose to an acute presentation of splenic rupture with associated haemorrhagic shock; which may initially be interpreted as septic shock. However, we demonstrate how insults such as sepsis and haemorrhagic shock may co-exist warranting careful consideration of possible dual pathologies in complex presentations which may be life-threatening. CONCLUSION: While the causal relationship between acute appendicitis and atraumatic spontaneous splenic rupture remains unclear, our case considers and highlights the importance of considering dual pathology in patients presenting in the acute setting. PMID- 27662217 TI - Adaptive PID control based on orthogonal endocrine neural networks. AB - A new intelligent hybrid structure used for online tuning of a PID controller is proposed in this paper. The structure is based on two adaptive neural networks, both with built-in Chebyshev orthogonal polynomials. First substructure network is a regular orthogonal neural network with implemented artificial endocrine factor (OENN), in the form of environmental stimuli, to its weights. It is used for approximation of control signals and for processing system deviation/disturbance signals which are introduced in the form of environmental stimuli. The output values of OENN are used to calculate artificial environmental stimuli (AES), which represent required adaptation measure of a second network orthogonal endocrine adaptive neuro-fuzzy inference system (OEANFIS). OEANFIS is used to process control, output and error signals of a system and to generate adjustable values of proportional, derivative, and integral parameters, used for online tuning of a PID controller. The developed structure is experimentally tested on a laboratory model of the 3D crane system in terms of analysing tracking performances and deviation signals (error signals) of a payload. OENN OEANFIS performances are compared with traditional PID and 6 intelligent PID type controllers. Tracking performance comparisons (in transient and steady-state period) showed that the proposed adaptive controller possesses performances within the range of other tested controllers. The main contribution of OENN OEANFIS structure is significant minimization of deviation signals (17%-79%) compared to other controllers. It is recommended to exploit it when dealing with a highly nonlinear system which operates in the presence of undesirable disturbances. PMID- 27662218 TI - 2-Heteroarylidene-1-indanone derivatives as inhibitors of monoamine oxidase. AB - In the present study a series of fifteen 2-heteroarylidene-1-indanone derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. These compounds are structurally related to series of heterocyclic chalcone derivatives which have previously been shown to act as MAO B specific inhibitors. The results document that the 2-heteroarylidene-1 indanones are in vitro inhibitors of MAO-B, displaying IC50 values of 0.0044 1.53MUM. Although with lower potencies, the derivatives also inhibit the MAO-A isoform with IC50 values as low as 0.061MUM. An analysis of the structure activity relationships for MAO-B inhibition indicates that substitution with the methoxy group on the A-ring leads to a significant enhancement in MAO-B inhibition compared to the unsubstituted homologues while the effect of the heteroaromatic substituent on activity, in decreasing order is: 5-bromo-2-furan>5 methyl-2-furan>2-pyridine~2-thiophene>cyclohexyl>3-pyridine~2-furan. It may therefore be concluded that 2-heteroarylidene-1-indanone derivatives are promising leads for the design of MAO inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders. PMID- 27662219 TI - The opportunities and challenges of the MSSP ACO program: a report from the field. AB - In this article, we seek to provide the first detailed description of a Medicare Shared Savings Program (MSSP) accountable care organization (ACO)'s actions and results to help increase understanding of the challenges and opportunities facing ACOs, and in particular, those comprised of a network of independent practices. Whether ACOs have been successful in delivering value has been the subject of much debate and speculation. What has been missing from this discussion is a look at the program from the frontlines and those who are launching and running MSSP ACOs. We hope to fill that gap. PMID- 27662221 TI - Cost-benefit of appointment-based medication synchronization in community pharmacies. AB - OBJECTIVES: To evaluate the cost-benefit of appointment-based medication synchronization (ABMS) offered in community pharmacies for patients taking chronic medications to prevent negative outcomes associated with hyperlipidemia, hypertension, and diabetes. STUDY DESIGN: Decision-tree analysis based on published literature and publicly available data. METHODS: Program benefits were based on linking published findings of improvements in medication adherence due to the implementation of an ABMS program to a claims-based study of disease related medical costs associated with different levels of adherence. The direct cost of the program-increased medication utilization as a result of improved adherence-was calculated from publicly available prescription pricing data. Benefit-cost ratios were assessed from a payer perspective over a 1-year time frame. RESULTS: Additional medication expenditures due to improved adherence associated with ABMS enrollment were offset by lower disease-specific medical costs. Medical savings per additional dollar spent on medications ranged from approximately $1 to $37 depending on the medication and medication class considered. ABMS was most cost-beneficial for metformin and statins. Sensitivity analyses showed that cost-benefit was significantly impacted by medication costs and any service fees associated with ABMS. CONCLUSIONS: ABMS programs have been shown to increase medication adherence in patients taking chronic medications. These programs were shown to have a significant cost-benefit for healthcare payers by reducing medical utilization and costs. Payers should consider supporting the provision of these programs in community pharmacies. PMID- 27662220 TI - Implications of evolving delivery system reforms for prostate cancer care. AB - OBJECTIVES: Prostate cancer treatment is a significant source of morbidity and healthcare spending. Evolving clinical data have supported expanding surveillance as a means to "right-size" treatment. Integrated delivery systems afford the possibility of hastening this objective. STUDY DESIGN: Retrospective cohort study of Medicare beneficiaries. METHODS: We used a 20% sample of national Medicare claims to assess the impact of healthcare integration on rates of treatment and potential overtreatment in men newly diagnosed with prostate cancer between 2007 and 2011. Rates were measured according to the extent of integration within a market (ie, none, low, intermediate, and high). Generalized estimating equations were used to assess the relationship between integration and utilization, adjusting for confounders. RESULTS: Rates of treatment declined across all markets (P <.01 for overall time trend), but the rate of decline was similar for the 4 market types (P = .27). In the most integrated markets, the rate decreased by 28.8%, or from 55.5 per 10,000 population in 2007 to 39.5 per 10,000 in 2011. After adjusting for confounders, men residing in the most integrated markets were 2.1% less likely to be treated with curative intent compared with those living in areas without integrated delivery systems (P = .04). However, rates of potential overtreatment were similar across all markets regardless of the level of integration (P = .21). CONCLUSIONS: Healthcare integration was associated with small declines in prostate cancer treatment in newly diagnosed men, but not with potential overtreatment. Integrated care alone may be insufficient to curtail potential overtreatment of prostate cancer. PMID- 27662223 TI - New strategies for aligning physicians with health system incentives. PMID- 27662222 TI - Geographic variation in surgical outcomes and cost between the United States and Japan. AB - OBJECTIVES: Unwarranted geographic variation in spending has received intense scrutiny in the United States. However, few studies have compared variation in spending and surgical outcomes between the United States healthcare system and those of other nations. In this study, we compare the geographic variation in postsurgical outcomes and cost between the United States and Japan. STUDY DESIGN: This retrospective cohort study uses Medicare Part A data from the United States (2010-2011) and similar inpatient data from Japan (2012). Patients 65 years or older undergoing 1 of 5 surgeries (coronary artery bypass graft, abdominal aortic aneurysm repair, colectomy, pancreatectomy, or gastrectomy) were selected in the United States and Japan. METHODS: Reliability- and case-mix-adjusted coefficient of variation (COV) values were calculated using hierarchical modeling and empirical Bayes techniques for the following 5 outcomes: postoperative mortality, the development of a complication, death after complication (failure to rescue), length of stay, and the cost of the hospitalization. Sensitivity analyses were also performed by calculating patient demographic-and case-mix-adjusted COV values for each outcome using weighted age- and sex-standardized values. RESULTS: The variability of the postsurgical outcomes was uniformly lower in the United States compared with Japan. Cost variation was consistently higher in the United States for all surgeries. CONCLUSIONS: Although the US healthcare system may be more inefficient regarding costs, the presence of higher geographic variation in postoperative care in Japan, relative to the United States, suggests that the observed geographic variation in the United States-both for health expenditures and outcomes-is not a unique manifestation of its structural shortcomings. PMID- 27662224 TI - Struggling with motherhood and coping with fatherhood - A grounded theory study among Thai teenagers. AB - OBJECTIVE: to gain a deeper understanding of Thai teenage parents' perspectives, experiences and reasoning about becoming and being a teenage parent from a gender perspective. DESIGN: an exploratory design using grounded theory methodology. Semi-structured interviews were used to collect data. An interview guide was developed, a pilot study was undertaken, and interviews were performed on two different occasions: once during the second trimester of pregnancy and again when the infant was 5-6 months old. SETTING: a province in the western part of Thailand. PARTICIPANTS: the selection of a heterogeneous group of teenage parents to-be continued until saturation was reached, as describe by Glaser and Strauss (1967), in all n=50. Inclusion criteria for participants were that they were heterosexual couples, under 20 years of age, cohabiting, and expecting their first child. FINDINGS: the core category 'struggling with motherhood and coping with fatherhood' comprises descriptions of the process from when the teenagers first learned about the pregnancy until the child was six months old. The teenagers had failed to use contraceptives which led to an unintended parenthood. Their parenthood became a turning point as the teenagers started to change their behaviours and lifestyle during pregnancy, and adapted their relationships to partner and family. Family commitments was a facilitator, through support given by their families. Finally, becoming a parent describes ways of dealing with the parental role, by engaging in parental activities and reestablishing goals in life. Most of the teenage parents reproduced traditional gender roles by being a caring mother or a breadwinning father respectively. KEY CONCLUSIONS: 'struggling with motherhood and coping with fatherhood' referred to the parents' stories about how they struggled and coped with life changes and their parental role when they became unintentionally pregnant, accepted their parenting, and finally became parents. After becoming parents, the main concerns of most of the teenage parents were being a caring mother and a breadwinning father. IMPLICATIONS FOR PRACTICE: this study contributes a deeper understanding of Thai teenage parents' experiences of becoming and being a parent and might improve health care professionals' adaptation of care for teentranatanage parents and inspire them to tailor their care specifically to teenager's needs from early pregnancy to parenthood. PMID- 27662226 TI - Gastric cancer mortality in a high-incidence area (Ardabil Province, Northwest Iran): What risk factors are causative? PMID- 27662225 TI - Response to the commentary letter entitled 'Diagnostic radiography and thyroid cancer - causation or simply an association?' to our article entitled 'Diagnostic radiography exposure increases the risk for thyroid microcarcinoma: a population based case-control study' that was published in the European Journal of Cancer Prevention 2015; 24(5):439-446. PMID- 27662227 TI - Appropriateness of Language Used in Patient Educational Materials from 24 National Anesthesiology Associations. AB - BACKGROUND: Patient education materials produced by national anesthesiology associations could be used to facilitate patient informed consent and promote the discipline of anesthesiology. To achieve these goals, materials must use language that most adults can understand. Health organizations recommend that materials be written at the grade 8 level or less to ensure that they are understood by laypersons. The authors, therefore, investigated the language of educational materials produced by anesthesiology associations. METHODS: Educational materials were downloaded from the Web sites of 24 national anesthesiology associations, as available. Materials were divided into eight topics, resulting in 112 separate passages. Linguistic measures were calculated using Coh-Metrix (version 3.0; Memphis, USA) linguistic software. The authors compared the measures to a grade 8 standard and examined the influence of both passage topic and country of origin using multivariate ANOVA. RESULTS: The authors found that 67% of associations provided online educational materials. None of the passages had all linguistic measures at or below the grade 8 level. Linguistic measures were influenced by both passage topic (F = 3.64; P < 0.0001) and country of origin (F = 7.26; P < 0.0001). Contrast showed that passages describing the role of anesthesiologists in perioperative care used language that was especially inappropriate. CONCLUSIONS: Those associations that provided materials used words that were long and abstract. The language used was especially inappropriate for topics that are critical to facilitating patient informed consent and promoting the discipline of anesthesiology. Anesthesiology associations should simplify their materials and should consider screening their materials with linguistic software before making them public. PMID- 27662229 TI - Substitution Boosts Charge Separation for High Solar-Driven Photocatalytic Performance. AB - Bandgap engineering of photocatalysts is a common approach to achieving high effective utilization of solar resource. However, the difficulty in achieving bandgap narrowing and high activity simultaneously seems to be irreconcilable via the traditional modification pathway. Herein, we have substituted iodine for a fraction of bromine atoms in BiOBr to overcome this restriction and provided some deep-seated insights into how the substitution boosts the photocatalytic properties. The substituted BiOBr0.75I0.25 exhibited exceptional photoactivity, with photon-to-current conversion efficiency approximately 6 times greater than TiO2 in UV region, and more than 10 times higher than BiOBr or BiOI in visible light region. We found that the substitution narrowed the bandgap, facilitated the diffusion of electron with small effective mass, as well as induced oxygen vacancies on [Bi2O2]2+ layers. By virtue of the stronger dipole moments produced, the enhancement of intrinsic electric fields between [Bi2O2]2+ and halogen slabs was achieved in BiOBr0.75I0.25; thereby the distance the photogenerated electron could diffuse was sufficient to inhibit the recombination. Our findings not only shed light on the potential properties of hybrid-halide photocatalysts but also provide a strategy for developing high efficiency catalysts. PMID- 27662230 TI - Stereoselective Access to 1-[2-Bromo(het)aryloxy]propan-2-amines Using Transaminases and Lipases; Development of a Chemoenzymatic Strategy Toward a Levofloxacin Precursor. AB - Two independent enzymatic strategies have been developed toward the synthesis of enantioenriched 1-[2-bromo(het)aryloxy]propan-2-amines. With that purpose a series of racemic amines and prochiral ketones have been synthesized from commercially available 2-bromophenols or brominated pyridine derivatives bearing different pattern substitutions in the aromatic ring. Biotransamination experiments have been studied using ketones as starting materials, yielding both the (R)- and (S)-amine enantiomers with high selectivity (91-99% ee) depending on the transaminase source. In a complementary approach, the classical kinetic resolutions of the racemic amines have been investigated using Candida antarctica lipase type B as biocatalyst. Ethyl methoxyacetate was found as a suitable acyl donor leading to the corresponding (S)-amines (90-99% ee) and (R)-amides (88-99% ee) with high selectivity in most of the cases. A preparative biotransamination process has been developed for the synthesis of (2S)-1-(6-bromo-2,3 difluorophenoxy)propan-2-amine in 61% isolated yield after 24 h, a valuable precursor of the antimicrobial agent Levofloxacin. PMID- 27662231 TI - The glycocins: in a class of their own. AB - First reported in 2011, glycocins (glycosylated bacteriocins) are bacterial toxins that constitute a subset of ribosomally synthesised and post translationally modified peptide (RiPP) natural products. Three NMR structures (glycocin F, ASM1 and sublancin 168), two with helix-loop-helix Cs alpha/alpha folds, are deposited in the PDB. Each structure contains a monosaccharide beta-S linked to a cysteine side chain. Three more glycocins (thurandacin, and enterocins F4-9 and 96) have been biochemically characterised, and others predicted on the basis of bioinformatic analyses. Only glycocin F, ASM1 and enterocin F4-9 are unequivocally glycoactive. This review probes the structure function relationships of four types of nested disulfide-bonded glycocins. PMID- 27662232 TI - Haematopoietic stem cell transplantation in inborn errors of metabolism. AB - PURPOSE OF REVIEW: This review summarizes the main results of haematopoietic stem cell transplantation (HSCT) in selected inborn errors of metabolism (IEMs). RECENT FINDINGS: Early diagnosis and immediate referral to an IEM specialist is of paramount importance to improve clinical outcome: patients who are transplanted early or in their presymptomatic phase generally achieve better correction of their somatic symptoms and neurocognitive development. Long-term outcome in children with Hurler syndrome is influenced by age at HSCT, baseline clinical status and post-HSCT enzyme levels. Myeloablative Busulfan-based conditioning regimens with therapeutic drug monitoring are recommended to achieve full donor engraftment and more robust enzyme delivery after HSCT. Gene therapy can lead to production of supranormal enzyme levels, and preliminary clinical results are also promising in IEMs historically not responsive to allogeneic HSCT. SUMMARY: Allogeneic HSCT has largely contributed to the improved survival and quality of life of many children affected by IEMs. Neonatal screening could enable earlier HSCT, and this might significantly reduce residual disease burden and improve clinical outcome. Novel strategies, such as gene therapy, have shown encouraging clinical results in selected IEMs and might become more widely available in the future, with potentially better enzyme delivery and reduced transplant-related toxicity. PMID- 27662233 TI - WHY THE DOTS ARE BLACK ONLY IN THE LATE PHASE OF THE INDOCYANINE GREEN ANGIOGRAPHY IN MULTIPLE EVANESCENT WHITE DOT SYNDROME. AB - PURPOSE: To determine what retinal layer is primarily involved in multiple evanescent white dot syndrome compared with acute posterior multifocal placoid pigment epitheliopathy using multimodal imaging including indocyanine green angiography. METHODS: Color fundus photographs and fluorescein angiography, ICGA and spectral domain optical coherence tomography images of two typical acute cases, one of acute posterior multifocal placoid pigment epitheliopathy and one of multiple evanescent white dot syndrome, were assessed and compared. RESULTS: In both diseases, white plaques or dots were seen at the posterior pole. The hypofluorescence of acute posterior multifocal placoid pigment epitheliopathy in the early phase of the fluorescein angiography and throughout the ICGA sequence suggested a multifocal choroidal hypoperfusion as the cause of the opacification of the outer retina corresponding to its hyper-reflectivity on spectral domain optical coherence tomography. In multiple evanescent white dot syndrome, there was no choroidal filling defect and the white spots were silent in the early phase of the ICGA, whereas they became black only in the late phase. The outer retina was also altered at the spots. CONCLUSION: In multiple evanescent white dot syndrome, the late hypofluorescence of the white spots on ICGA was likely due to the absence of ICG uptake by a damaged retinal pigment epithelium. Multiple evanescent white dot syndrome seems as a primary reversible nondestructive retinal pigment epitheliopathy, whereas acute posterior multifocal placoid pigment epitheliopathy is a true choroidopathy. PMID- 27662234 TI - QUININE TOXICITY: MULTIMODAL RETINAL IMAGING AND ELECTRORETINOGRAPHY FINDINGS. AB - PURPOSE: To report the multimodal retinal imaging and electroretinography (ERG) findings of two cases with quinine toxicity. METHODS: Retrospective case series describing the retinal imaging and ERG findings in two patients with retinal toxicity due to remote quinine exposure. Color fundus photography, fundus autofluorescence, spectral domain optical coherence tomography, and full-field ERG findings are described. RESULTS: Two patients with longstanding decreased vision were found to have bilateral optic disk pallor and retinal vascular attenuation indicative of chronic sequela after acute quinine toxicity. Inner retinal atrophy was identified on spectral domain optical coherence tomography, and full-field ERG was consistent with generalized inner retinal dysfunction in both patients. Fundus autofluorescence failed to demonstrate any evidence of outer retinal or retinal pigment epithelial abnormalities. CONCLUSION: Quinine toxicity may be associated with vision loss secondary to inner retinal atrophy. We report two cases with a clear history of acute quinine exposure leading to similar retinal imaging findings and distinctive ERG abnormalities. Clinicians should be aware of this uncommon condition as ingestion history may be remote. PMID- 27662235 TI - Double hydrogen bond interaction in 7-azaindole complexes with protic solvents. AB - The double hydrogen bond interaction between 7-azaindole (7AI) and protic solvents including methanol (MeOH), formamide (FM), formic acid (FA), pyridone (PY) and 7AI has been investigated as a proper model of mutations generated by tautomeric shifts in hydrogen-bonded bases of DNA. The results confirm electrostatic nature for all considered hydrogen bonds except for NH hydrogen bond in 7AI-FA. The largest interaction and polarization energies are obtained for 7AI-FA by means of energy decomposition analyses (EDA). The EDA results show an inverse competitive correlation between polarization and electrostatic components of attraction energy to determine the nature of hydrogen bond. The red shifted hydrogen bonds are identified for all complexes as a result of hyperconjugation, except for 7AI-MeOH, which its blue-shift effect is attributed to the rehybridization dominating of CH bond. Investigation of aromaticity indices for 7AI complexes represents an increase in aromaticity of pentagonal ring and a decrease in hexagonal ring. Finally, the double hydrogen bond between 7AI and FA is identified as dominant interaction to achieve the tautomerization of 7AI in all applied approaches. PMID- 27662236 TI - Self-Assembled Nanogels of Cholesterol-Bearing Hydroxypropyl Cellulose: A Thermoresponsive Building Block for Nanogel Tectonic Materials. AB - Hydroxypropyl cellulose (HPC) is a fascinating polysaccharide to use in developing a nanogel to be a thermoresponsive building unit for nanogel tectonic materials. Cholesterol-bearing HPC (Ch-HPC) self-assembled to form nanogels through hydrophobic interactions of the cholesteryl groups in water. Ch-HPC nanogels had a lower critical solution temperature in line with that of native HPC. The particle size of Ch-HPC nanogels was reversibly controlled by the temperature and salting-out effect. The thermoresponsive property was also observed in Ch-HPC nanogel-cross-linked macrogels. These results suggest that a Ch-HPC nanogel is an attractive building block for thermoresponsive nanogel tectonic materials. PMID- 27662237 TI - Explicitly Unraveling the Roles of Counterions, Solvent Molecules, and Electron Correlation in Solution Phase Reaction Pathways. AB - Studies utilizing continuum solvation methods can sometimes omit critically important solute-solvent interactions, while explicitly sampling full solution phase mechanisms accurately with Born-Oppenheimer molecular dynamics (BOMD) is computationally costly. In this work, we benchmark components for an alternative IRCMax-like procedure for refined analyses of electronic energies along reaction pathways. The procedure involves obtaining molecular clusters from nudged elastic band calculations for use in mixed explicit-continuum models. The reaction energetics from these models correspond well to energetics obtained from explicit models using periodic boundary conditions, and the clusters obtained are more amenable to treatments with high levels of quantum chemistry theory. We demonstrate this approach using CO2 reduction by NaBH4 and NaBH3OH in aqueous solution as test cases. We show that the local solvation environment containing explicit solvent molecules and a counterion within the entire first solvation shell significantly influences reaction energies. For the hydride transfers reported herein, the level of quantum chemistry theory used beyond that treated by standard GGA exchange correlation functionals normally plays a less significant role. PMID- 27662238 TI - Tandem O-H Insertion/[1,3]-Alkyl Shift of Rhodium Azavinyl Carbenoids with Benzylic Alcohols: A Route To Convert C-OH Bonds into C-C Bonds. AB - Alcohols are among the most abundant and commonly used organic feedstock in industrial processes and academic research. The first tandem O-H insertion/[1,3] alkyl shift reaction reported is between benzylic alcohols and rhodium azavinyl carbenoids derived from N-sulfonyl-1,2,3-triazoles, which provides a strategically novel way of cleaving C-OH bonds and forming C-C bonds. The substrate scope is broad, capable of covering 1 degrees -, 2 degrees -, and 3 degrees -benzylic alcohols. Moreover, it constitutes a new and powerful synthetic method for constructing alpha-aminoketones. Mechanistic studies suggest that a [1,3]-alkyl shift of oxonium ylides is responsible for cleavage of the C-OH bonds. PMID- 27662239 TI - Hollow Porous Hierarchical-Structured 0.5Li2MnO3.0.5LiMn0.4Co0.3Ni0.3O2 as a High Performance Cathode Material for Lithium-Ion Batteries. AB - We report a novel hollow porous hierarchical-architectured 0.5Li2MnO3.0.5LiMn0.4Co0.3Ni0.3O2 (LLO) for lithium-ion batteries (LIBs). The obtained lithium-rich layered oxides possess a large inner cavity, a permeable porous shell, and excellent structural robustness. In LIBs, such unique features are favorable for fast Li+ transportation and can provide sufficient contact between active materials and electrolytes, accommodate more Li+, and improve the kinetics of the electrochemical reaction. The as-prepared LLO displays an extremely high initial discharge capacity (296.5 mAh g-1 at 0.2 C), high rate capability (162.6 mAh g-1 at 10 C), and excellent cycling stability (237.6 mAh g 1 after 100 cycles at 0.5 C and 153.8 mAh g-1 after 200 cycles at 10 C). These values are superior to most literature data. PMID- 27662240 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS - 2016. AB - ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX(r) = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization. PMID- 27662241 TI - A mixed-methods process evaluation of a goal management intervention for patients with polyarthritis. AB - Process evaluations of newly developed interventions are necessary to identify effective and less effective intervention components. First aim of this study was to identify key components of a psychosocial goal management intervention from the perspective of participants, and second aim was to evaluate the intervention's fidelity. A mixed-methods approach was applied to 24 interviews with participants post-intervention and 16 audio recordings of random training sessions. Participants experienced three key components: (1) the content, in which specific exercises helped to raise awareness and (intention to) change goal management behaviour, (2) person-focused approach, specifically, the nurse as trainer and personal fit of the approach, and (3) social mechanisms, including facilitating group processes and interpersonal processes. Adherence to the protocol by the trainers was high, while differences were found in the degree to which they were able to apply the intended collaborative approach and psychological communication skills. The applied design provided valuable insights into the processes that took place. Both the effects experienced by participants in relationship to the content, approach and social mechanisms as well as the strengths and weaknesses found with regard to fidelity provide insights that can inform the development and implementation of person-focused interventions. PMID- 27662242 TI - Protecting Triazabutadienes To Afford Acid Resistance. AB - Recent work on triazabutadienes has shown that they have the ability to release aryl diazonium ions under exceptionally mild acidic conditions. There are instances that require that this release be prevented or minimized. Accordingly, a base-labile protection strategy for the triazabutadiene is presented. It affords enhanced synthetic and practical utility of the triazabutadiene. The effects of steric and electronic factors in the rate of removal are discussed, and the triazabutadiene protection is shown to be compatible with the traditional acid-labile protection strategy used in solid phase peptide synthesis. PMID- 27662243 TI - A micromolar concentration of lipo-chitooligosaccharide (Nod Bj V [C18:1, MeFuc]) regulates the emergence and seed productivity of rapid cycling canola (Brassica napus [L.]) plants. AB - The objective of this experiment was to assess whether or not the application of lipo-chitooligosaccharide (Nod Bj V [C18:1, MeFuc]) (LCO) would increase yield factors under conditions that would inhibit canola (Brassica napus L.) productivity. The seed application reduced the percentage of plants that were unproductive by 15.10% compared to plants grown from untreated seeds. Based on the 95% confidence interval for the difference, untreated plants would produce 38 to 3% fewer seeds than plants grown from LCO treated seeds. The experimental conditions were artificial, but further experimentation, with agricultural cultivars grown in greenhouses where natural conditions were simulated, confirmed that LCO treatment can contribute to canola yield. PMID- 27662244 TI - Subclinical ultrasonographic abnormalities of the suspensory ligament branches in National Hunt racehorses. AB - BACKGROUND: Suspensory ligament branch (SLB) desmopathy is a common cause of lameness and an important cause of lost training in the Thoroughbred racing industry. Studies have assessed the impact of insertional injuries of the SLB on the careers of flat racehorses and established the prevalence of subclinical ultrasonographic SLB abnormalities in this population, but little work has investigated SLB injury in National Hunt (NH) racehorses. OBJECTIVES: To investigate the prevalence of subclinical ultrasonographic SLB abnormalities in NH racehorses with no clinical signs or history of SLB injury and to establish the cross-sectional area (CSA) of SLBs in this population. STUDY DESIGN: Cross sectional study using data collected from horses on an NH yard. METHODS: Ultrasonographic examination of forelimb SLBs in 62 horses on a single NH yard was performed. Images were graded according to a previously reported system. CSA measurements were obtained from transverse images. RESULTS: Nineteen of 62 horses had at least one SLB with grade 2 ultrasonographic abnormalities. Grade 2 ultrasonographic abnormalities occurred more frequently in the medial than the lateral SLB (P = 0.05). The medial SLB insertional CSA was significantly larger (P<0.001) than that of the lateral SLB. MAIN LIMITATIONS: Length of time on the yard (and therefore available veterinary history) is variable in this population. CONCLUSIONS: One in three NH racehorses without history or clinical signs of SLB injury had at least one SLB with a grade 2 ultrasonographic abnormality. The medial branch was over-represented. The medial SLB insertional CSA is larger than the lateral and thus comparison with the corresponding branch in the contralateral limb is recommended to avoid misdiagnosis of medial SLB enlargement. PMID- 27662245 TI - MED28 Regulates Epithelial-Mesenchymal Transition Through NFkappaB in Human Breast Cancer Cells. AB - MED28, a mammalian Mediator subunit, was found highly expressed in several types of malignancy, including breast cancer. Recently, we have identified a role of MED28 in regulating both cell growth and migration in human breast cancer cells. In epithelium-derived solid tumor, migration and invasion are preceded by the progression of epithelial-mesenchymal transition (EMT) which calls for downregulation of epithelial markers as well as upregulation of mesenchymal markers, among other features. The objective of this study was to investigate a putative role of MED28 in the progression of EMT in human breast cancer cells. In fibroblast-like MDA-MB-231 cells, suppression of MED28 attenuated the mesenchymal morphology, concomitantly with a reduction of several mesenchymal biomarkers and Snail, a transcriptional repressor of E-cadherin. The suppression effect was also accompanied by downregulation of p-NFkappaB/p65. However, overexpression of MED28 exhibited in an opposite manner. In epithelial MCF7 cells, administration of Adriamycin(r), an experimental EMT induction system, led to a mesenchyme-like appearance correlated with increased expression of MED28, p-p65, and Snail, and a reciprocal change of epithelial and mesenchymal markers. Furthermore, suppression of MED28 attenuated the experimental EMT effect and restored the original expression status of E-cadherin and MMP9 in MCF7 cells. Our data indicate that MED28 modulates the development of EMT through NFkappaB in human breast cancer cells, further reinforcing the significance of MED28 in the progression of breast cancer on top of its role in cell growth and migration. J. Cell. Physiol. 232: 1337-1345, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662246 TI - Alterations of CorTFL1 and CorAP1 expression correlate with major evolutionary shifts of inflorescence architecture in Cornus (Cornaceae) - a proposed model for variation of closed inflorescence forms. AB - TFL1-, AP1- and LFY-like genes are known to be key regulators of inflorescence development. However, it remains to be tested whether the evolutionary modifications of inflorescence morphology result from shifts in their expression patterns. We compared the spatiotemporal expression patterns of CorTFL1, CorAP1 and CorLFY in six closely related Cornus species that display four types of closed inflorescence morphology using quantitative real-time polymerase chain reaction (qRT-PCR) and RNA in situ hybridization. Character mapping on the phylogeny was conducted to identify evolutionary changes and to assess the correlation between changes in gene expression and inflorescence morphology. Results demonstrated variation of gene expression patterns among species and a strong correlation between CorTFL1 expression and the branch index of the inflorescence type. Evolutionary changes in CorTFL1 and CorAP1 expression co occurred on the phylogeny with the morphological changes underpinning inflorescence divergence. The study found a clear correlation between the expression patterns of CorTFL1 and CorAP1 and the inflorescence architecture in a natural system displaying closed inflorescences. The results suggest a role for the alteration in CorTFL1 and CorAP1 expression during the evolutionary modification of inflorescences in Cornus. We propose that a TFL1-like and AP1 like gene-based model may explain variation of closed inflorescences in Cornus and other lineages. PMID- 27662247 TI - It Takes a Megalopolis to Relaunch a Journal: A Story of Gratitude. PMID- 27662248 TI - Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology. AB - Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our September 2016 selection includes the discovery of PZM21, a MUOR biased agonist with minimal side effects, and the role of cholesterol in Hedgehog signaling pathway. PMID- 27662249 TI - A New Staple: Peptide-Targeted Covalent Inhibitors. AB - In this issue of Cell Chemical Biology, Huhn et al. (2016) unveil a clever strategy for selectively and irreversibly inhibiting an anti-apoptotic protein, BFL-1. The authors describe stapled peptides bearing carefully placed electrophiles that target a unique cysteine residue in BFL-1 via covalent modification, thus representing an extension of the stapled peptide concept into the covalent inhibitor space. PMID- 27662250 TI - Lipase Processing of Complex Lipid Antigens. AB - Mycobacterium tuberculosis synthesizes a wide variety of complex lipids that can serve as antigens in immune recognition of the bacterium. In this issue of Cell Chemical Biology, Gilleron et al. (2016) identify key enzymes essential for lipid antigen processing, which is required for CD1b-restricted T cell activation. PMID- 27662251 TI - Vaccinology Gets Help from Chemistry. AB - A recent report on the immunological activity of protein conjugates of synthetic lipoteicoic fragments from Clostridium difficile underpins the use of these molecules for the development of a vaccine. In a recent issue of Cell Chemical Biology, Broecker et al. (2016) illustrate the utility of glycoarray-based selection of bacterial carbohydrates with the potential to become vaccine candidates. PMID- 27662252 TI - Synthetic Biology-Based Point-of-Care Diagnostics for Infectious Disease. AB - Infectious diseases outpace all other causes of death in low-income countries, posing global health risks, laying stress on healthcare systems and societies, and taking an avoidable human toll. One solution to this crisis is early diagnosis of infectious disease, which represents a powerful way to optimize treatment, increase patient survival rate, and decrease healthcare costs. However, conventional early diagnosis methods take a long time to generate results, lack accuracy, and are known to seriously underperform with regard to fungal and viral infections. Synthetic biology offers a fast and highly accurate alternative to conventional infectious disease diagnosis. In this review, we outline obstacles to infectious disease diagnostics and discuss two emerging alternatives: synthetic viral diagnostic systems and biosensors. We argue that these synthetic biology-based approaches may overcome diagnostic obstacles in infectious disease and improve health outcomes. PMID- 27662253 TI - Stabilizing Protein Motifs with a Genetically Encoded Metal-Ion Chelator. AB - The N-peptide of HIV gp41 forms a trimeric coiled-coil intermediate during host cell-viral fusion. Stable mimics of this coiled coil could potentially serve as HIV vaccine candidates or inhibitors of viral entry. Therefore, a variety of approaches have been investigated to maintain the N-peptide in its trimeric helical conformation. Here, we utilize a genetic method to incorporate the metal chelating noncanonical amino acid (2,2'-bipyridin-5-yl)alanine (BpyAla) into IZN17, an established trimeric coiled-coil gp41 model. We demonstrate that BpyAla IZN17 acquires Fe(II) during expression in Escherichia coli, resulting in the formation of a highly stable IZN17 helical trimer with a Tm > 95 degrees C. Removal of Fe(II) results in a 27 degrees C decrease in thermal stability. Replacement of Fe(II) with Zn(II) also affords a Tm > 90 degrees C. Thus, the genetic introduction of BpyAla into polypeptide provides a straightforward method for stabilizing coiled-coil structural motifs in recombinantly engineered proteins. PMID- 27662254 TI - Lysosomal Lipases PLRP2 and LPLA2 Process Mycobacterial Multi-acylated Lipids and Generate T Cell Stimulatory Antigens. AB - Complex antigens require processing within antigen-presenting cells (APCs) to form T cell stimulatory complexes with CD1 antigen-presenting molecules. It remains unknown whether lipids with multi-acylated moieties also necessitate digestion by lipases to become capable of binding CD1 molecules and stimulate T cells. Here, we show that the mycobacterial tetra-acylated glycolipid antigens phosphatidyl-myo-inositol mannosides (PIM) are digested to di-acylated forms by pancreatic lipase-related protein 2 (PLRP2) and lysosomal phospholipase A2 (LPLA2) within APCs. Recombinant PLRP2 and LPLA2 removed the sn1- and sn2-bound fatty acids from the PIM glycerol moiety, as revealed by mass spectrometry and nuclear magnetic resonance studies. PLRP2 or LPLA2 gene silencing in APCs abolished PIM presentation to T cells, thus revealing an essential role of both lipases in vivo. These findings show that endosomal lipases participate in lipid antigen presentation by processing lipid antigens and have a role in T cell immunity against mycobacteria. PMID- 27662255 TI - Rhodium-Catalyzed Oxidative Benzannulation of N-Pivaloylanilines with Internal Alkynes through Dual C-H Bond Activation: Synthesis of Highly Substituted Naphthalenes. AB - An efficient method was developed for the synthesis of highly substituted naphthalenes through rhodium-catalyzed oxidative benzannulation of N pivaloylanilines with internal alkynes. The benzannulation reaction proceeded smoothly through dual C-H bond activation to produce the corresponding highly substituted naphthalene products in satisfactory to good yields. PMID- 27662256 TI - Invasion history and demographic processes associated with rapid morphological changes in the Red-whiskered bulbul established on tropical islands. AB - The Red-whiskered bulbul is a very successful invasive bird species. Morphological differences have been reported among individuals inhabiting the humid and dry coasts of Reunion Island, in a 30-year-old population. This suggests a capacity for rapid local adaptation which could explain the general invasive success of this species. However, the origin and invasion history of this population is unknown. It is therefore not possible to establish with certainty the cause of these morphological differences. Here, we investigated the invasion history of populations of Red-whiskered bulbul established on Reunion Island, Mauritius and Oahu (three geographically similar tropical islands) to assess the link between invasion history and morphological changes in these populations. We first assessed the source(s) of the invasive populations. We then compared the morphology of the individuals between the invasive and native populations and between the dry and humid coasts of invaded islands. Finally, we inferred the invasion history of the invasive populations to investigate the role of neutral processes (e.g. founder effect and drift) on morphology. We found that the invasive populations have a similar origin and that the morphology of the individuals in these populations has diverged in a similar way from the native range, suggesting a convergent adaptation to tropical islands. Like on Reunion, we found differences in morphology between the dry and humid coasts on Mauritius. These morphological differences can be explained by invasion history on Reunion but not on Mauritius. Both neutral evolution and adaptation thus shape the morphology of invasive Red-whiskered bulbuls. PMID- 27662258 TI - Towards a universally accepted definition of subclinical Cushing's syndrome - subclinical autonomous hypercortisolism. PMID- 27662257 TI - Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop. AB - Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardization. A new strategy to standardize MP counts by flow cytometry was evaluated in a multicenter study. No difference was found between instruments using forward or side scatter as the trigger parameter. This study demonstrated that beads can be used as a standardization tool for MPs. Click to hear the ISTH Academy's webinar on microvesicles SUMMARY: Background Microparticles (MPs) are extracellular vesicles resulting from the budding of cellular membranes that have a high potential as emergent biomarkers; however, their clinical relevance is hampered by methodological enumeration concerns and a lack of standardization. Flow cytometry (FCM) remains the most commonly used technique with the best capability to determine the cellular origin of single MPs. However, instruments behave variably depending on which scatter parameter (forward (FSC) or side scatter (SSC)) provides the best resolution to discriminate submicron particles. To overcome this problem, a new approach, based on two sets of selected beads adapted to FSC or SSC-optimized instruments, was recently proposed to reproducibly enumerate platelet-derived MP counts among instruments with different optical systems. Objective The objective was to evaluate this strategy in an international workshop that included 44 laboratories accounting for 52 cytometers of 14 types. Methods/Results Using resolution capability and background noise level as criteria to qualify the instruments, the standardization strategy proved to be compatible with 85% (44/52) of instruments. All instruments correctly ranked the platelet MP (PMP) levels of two platelet free plasma samples. The inter-laboratory variability of PMP counts was 37% and 28% for each sample. No difference was found between instruments using forward or side-scattered light as the relative sizing parameter. Conclusions Despite remaining limitations, this study is the first to demonstrate a real potential of bead-based strategies for standardization of MP enumeration across different FCM platforms. Additional standardization efforts are still mandatory to evaluate MPs' clinical relevance at a multicenter level. PMID- 27662260 TI - Tracer diffusion in a polymer gel: simulations of static and dynamic 3D networks using spherical boundary conditions. AB - We have investigated an alternative to the standard periodic boundary conditions for simulating the diffusion of tracer particles in a polymer gel by performing Brownian dynamics simulations using spherical boundary conditions. The gel network is constructed by randomly distributing tetravalent cross-linking nodes and connecting nearest pairs. The final gel structure is characterised by the radial distribution functions, chain lengths and end-to-end distances, and the pore size distribution. We have looked at the diffusion of tracer particles with a wide range of sizes, diffusing in both static and dynamic networks of two different volume fractions. It is quantitatively shown that the dynamical effect of the network becomes more important in facilitating the diffusional transport for larger particle sizes, and that one obtains a finite diffusion also for particle sizes well above the maximum in the pore size distribution. PMID- 27662259 TI - Environment not dispersal limitation drives clonal composition of Arctic Daphnia in a recently deglaciated area. AB - One of the most prominent manifestations of the ongoing climate warming is the retreat of glaciers and ice sheets around the world. Retreating glaciers result in the formation of new ponds and lakes, which are available for colonization. The gradual appearance of these new habitat patches allows us to determine to what extent the composition of asexual Daphnia (water flea) populations is affected by environmental drivers vs. dispersal limitation. Here, we used a landscape genetics approach to assess the processes structuring the clonal composition of species in the D. pulex species complex that have colonized periglacial habitats created by ice-sheet retreat in western Greenland. We analysed 61 populations from a young (<50 years) and an old cluster (>150 years) of lakes and ponds. We identified 42 asexual clones that varied widely in spatial distribution. Beta-diversity was higher among older than among younger systems. Lineage sorting by the environment explained 14% of the variation in clonal composition whereas the pure effect of geographical distance was very small and statistically insignificant (Radj2 = 0.010, P = 0.085). Dispersal limitation did not seem important, even among young habitat patches. The observation of several tens of clones colonizing the area combined with environmentally driven clonal composition of populations illustrates that population assembly of asexual species in the Arctic is structured by environmental gradients reflecting differences in the ecology of clones. PMID- 27662261 TI - Children's medicine: What do consumers really want to know? AB - AIM: This study explored consumer knowledge gaps and concerns regarding medication use in children. METHODS: Calls concerning or made by people under 18 to the pharmacist-operated, national consumer medicines call centre National Prescribing Service Medicines Line (2002 to June 2010) were analysed. Calls were classified and narratively explored by age group: <1, 1-4, 5-14 and 15-17 years. Consumer Medication Information (CMI) and evidence-based resources were examined to determine information concordance for common questions. RESULTS: There were 14 753 paediatric-related calls (mean age 4.1 years). Callers were predominantly female (91.5%), mean age was 35.8 years. Most (89.4%) phoned for a child and 2.2% for themselves. Main enquiry types were: lactation (22.1%), treatment/prophylaxis (11.1%), dose (10.2%), adverse reaction (10.0%), interaction (8.4%) and vaccination (8.4%). However, the primary enquiry differed by age group: lactation (<1 year), dosing (1-4, 5-14 years) and interactions (15-17 years). Global concerns were medication safety, with breastfeeding for infants <1 year and age/weight dose clarification for children 1-4 and 5-14 years. In contrast, interaction questions from adolescents concerned nervous system medicines, cold/flu products, contraceptives and recreational drugs. While paracetamol was the primary medication of interest across age groups, the remaining 'top two' differed significantly. Inconsistencies identified between CMI and evidence-based resources contribute to consumer uncertainty. CONCLUSIONS: Care givers and older children use a call centre to address their information needs about frequently used and highly accessible medicines, and their concerns vary across paediatric age groups. Inconsistent information provided by CMI on medication use in children contributes to consumer uncertainty and help-seeking behaviour. PMID- 27662262 TI - Does the cause of the mild traumatic brain injury affect the expectation of persistent postconcussion symptoms and psychological trauma? AB - INTRODUCTION: A controlled experiment of the effect of injury cause on expectations of outcome from mild traumatic brain injury (TBI) was conducted. METHOD: Ninety-three participants were randomly assigned to one of four conditions. The participants read a vignette that described a mild TBI (with fixed injury parameters) from a different cause (sport, domestic assault, fall, or motor vehicle accident). The effect of the manipulation on expectations of persistent postconcussion symptoms and psychological trauma was assessed with standard measures and a novel "threat-to-life" measure. RESULTS: The Kruskal Wallis H test for group differences revealed a significant but selective effect of group on symptom and trauma outcomes (n2s >= .10; large effects). Post hoc pairwise tests showed that, in most cases, there was an expectation of a worse outcome following mild TBI from a domestic assault than from the other causes (small-to-medium effects). CONCLUSION: Expectations were selectively altered by an experimental manipulation of injury cause. Given that expectations of outcome are known to affect mild TBI prognosis, the findings suggest the need for greater attention to injury cause. PMID- 27662263 TI - Breast care screening for underserved African American women: Community-based participatory approach. AB - Traditional health promotion models often do not take into account the importance of shared cultural backgrounds, beliefs, and experiences unique to underserved African American women when designing community-based cancer screening and prevention programs. Thus, the purpose of this study was the development, implementation, and evaluation of a community-based participatory research (CBPR) program designed to increase breast cancer screening awareness in an underserved African American population by providing culturally appropriate social support and information. The study includes 357 African American women who participated in the program and completed the 6-month follow-up questionnaire. The program consisted of a 45-minute play, using community members and storytelling to honor and incorporate five different cultural experiences (skits) with breast care and cancer. Overall, findings indicate that the educational intervention was effective. In addition, these findings are consistent with the literature that suggests that educational interventions that include knowledge to alleviate concerns, dispel myths, and create awareness can increase breast cancer screening participation rates. Furthermore, these findings confirm the importance of CBPR in health promotion activities in reducing health and cancer disparities. PMID- 27662264 TI - Pharmacokinetics of guaifenesin, pseudoephedrine and hydrocodone in a combination oral liquid formulation, administered as single and multiple doses in healthy Chinese volunteers, and comparison with data for individual compounds formulated as Antuss(r). AB - 1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss(r). 2. In the single-dose period, exposure levels (AUC and Cmax) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15 mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (~0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24 h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering Cmax, there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss(r). 3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds. PMID- 27662265 TI - Development of a Communication Intervention for Older Adults With Limited Health Literacy: Photo Stories to Support Doctor-Patient Communication. AB - Successful doctor-patient communication relies on appropriate levels of communicative health literacy, the ability to deal with and communicate about health information. This article aims to describe the development of a narrative- and picture-based health literacy intervention intended to support older patients with limited health literacy when communicating during their primary care consultations. We performed a formative evaluation that included a review of the literature and interviews with stakeholders on relevant health literacy issues, qualitative studies with the target group, intervention planning, and a small scale evaluation. Cocreation with the target group was a major component. Seven photo stories were developed incorporating principles from narrative and social learning theory and covering communication themes and strategies identified during focus group discussions and role-play exercises. The intervention was developed in 3 different formats: 1-page photo stories, narrated video clips using the original photo story pictures, and interactive video clips covering participation and communication during primary care consultations. In our small scale evaluation, older adults considered the cocreated intervention appealing and comprehensible. The intervention shows promise for improving the health of older adults but needs further evaluation. This study provides a rigorous template for the participatory development of health literacy interventions. PMID- 27662266 TI - The role of three-dimensional pure bovine gelatin scaffolds in tendon healing, modeling, and remodeling: an in vivo investigation with potential clinical value. AB - AIM OF THE STUDY: Large tendon defects involving extensive tissue loss present complex clinical problems. Surgical reconstruction of such injuries is normally performed by transplanting autogenous and allogenous soft tissues that are expected to remodel to mimic a normal tendon. However, the use of grafts has always been associated with significant limitations. Tissue engineering employing artificial scaffolds may provide acceptable alternatives. Gelatin is a hydrolyzed form of collagen that is bioactive, biodegradable, and biocompatible. The present study has investigated the suitability of gelatin scaffold for promoting healing of a large tendon-defect model in rabbits. MATERIALS AND METHODS: An experimental model of a large tendon defect was produced by partial excision of the Achilles tendon of the left hind leg in adult rabbits. To standardize and stabilize the length of the tendon defect a modified Kessler core suture was anchored in the sectioned tendon ends. The defects were either left untreated or filled with three-dimensional gelatin scaffold. Before euthanasia 60 days after injury, the progress of healing was evaluated clinically. Samples of healing tendon were harvested at autopsy and evaluated by gross, histopathologic, scanning, and transmission electron microscopy, and by biomechanical testing. RESULTS: The treated animals showed superior weight-bearing and physical activity compared with those untreated, while frequency of peritendinous adhesions around the healing site was reduced. The gelatin scaffold itself was totally degraded and replaced by neo-tendon that morphologically had significantly greater numbers, diameters, density, and maturation of collagen fibrils, fibers, and fiber bundles than untreated tendon scar tissue. It also had mechanically higher ultimate load, yield load, stiffness, maximum stress and elastic modulus, when compared to the untreated tendons. CONCLUSION: Gelatin scaffold may be a valuable option in surgical reconstruction of large tendon defects. PMID- 27662268 TI - Evidence that subclinical somatoform dissociation is not characterised by heightened awareness of proprioceptive signals. AB - INTRODUCTION: It has been suggested that abnormal perceptual processing and somatosensory amplification may be contributory factors to somatoform symptom reporting. A key source of somatosensory information is proprioception, yet the perception and integration of this sense has not been sufficiently investigated in those prone to somatoform disorders. METHODS: Subclinical groups of high- and low-scorers on the Somatoform Dissociation Questionnaire made judgements about the location of their unseen hand following congruent or incongruent visuo proprioceptive feedback, which was manipulated using a MIRAGE-mediated reality system. RESULTS: No differences were found between groups, with both groups displaying normal proprioceptive accuracy under congruent conditions and equivalent visuo-proprioceptive integration under incongruent conditions. CONCLUSIONS: The results suggest that amplification of, or abnormal weighting for, proprioceptive signals is not a contributing factor to somatoform symptom reporting. PMID- 27662267 TI - Body size at birth and coronary heart disease-related hospital care in adult men findings from the Helsinki Birth Cohort Study. AB - AIM: We investigated, among those who had been hospitalized at least once due to coronary heart disease (CHD), the relationship between ponderal index (PI, birthweight/length3) at birth, a measure of thinness, and the age at first hospitalization due to CHD, the number of CHD-related hospital care episodes, and cost of CHD-related hospital care from young adulthood to old age. METHODS AND RESULTS: Data from the Helsinki Birth Cohort Study included 964 men born in Helsinki, Finland during 1934-1944, who had been hospitalized due to CHD and had birth anthropometrics data. PI (kg/m3) was categorized into low (<25.0), medium (25.0-27.5), and high (>27.5). CHD-related hospital care data were available from 1971 to 2013. We observed an earlier onset of (p = .014 for linearity) and a higher rate of CHD-related hospital care episodes among those in the lowest PI group (incidence rate ratio: 1.35 [95% confidence interval: 1.16-1.59, p < .001]), compared to the highest PI group. CHD-related hospital care costs in the lowest PI group were 25% (p = .001, 4% to 46%) higher compared to those in the highest PI group. DISCUSSION: Thinness at birth is associated with earlier onset, higher prevalence, and higher accumulated costs of CHD-related hospital in patient care among men who developed CHD. KEY MESSAGES Findings from this large birth cohort indicate that the onset of coronary heart disease (CHD)-related hospital in-patient care occurred at younger age during the 42-year time period among men who were born thin. Lower ponderal index (PI) was associated with a higher rate of CHD-related hospital in-patient care during the time period. We observed a linear increase in CHD-related hospital in-patient care costs across PI groups. PMID- 27662269 TI - Breaking Hepatitis B Virus Tolerance and Inducing Protective Immunity Based on Mimicking T Cell-Independent Antigen. AB - There are over 350 million chronic carriers of hepatitis B virus (HBV) in the world, of whom about a third eventually develop severe HBV-related complications. HBV contributes to liver cirrhosis and hepatocellular carcinoma development. Remarkable progress has been made in selective inhibition of HBV replication by nucleoside analogs. However, how to generate protective antibody of HBsAb in HBV infected patients after HBV-DNA becomes negative still remains a challenge for scientists. In this study, we show that OmpC-HBsAg 'a' epitope chimeric protein vaccine can break HBV tolerance and induce protective immunity in HBV transgenic mice based on mimicking T cell-independent antigen to bypass T cells from the adaptive immune system. The antibodies induced by the vaccine have the ability to prevent HBV virion infection of human hepatocytes. PMID- 27662270 TI - Correlations Between the SF-36, the Oswestry-Disability Index and Rolland-Morris Disability Questionnaire in Patients Undergoing Lumbar Decompression According to Types of Spine Origin Pain. AB - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine the correlation between SF-36 (a measure for overall health status in patients) and Oswestry Disability Index (ODI) or Rolland-Morris Disability Questionnaire (RMDQ) confined to spine according to the type of pain from the spine. SUMMARY OF BACKGROUND DATA: Data showed moderate correlation between ODI and SF-36 Physical Component Score (PCS), Physical Functioning (PF) (r=-0.46), Physical Role Functioning (RP) (r=-0.284), Bodily Pain (BP) (r=-0.327), and Mental Component Score (MCS), Emotional Role Functioning (r=-0.250), Social Role Functioning (r=0.254), Vitality (r=0.296). MATERIALS AND METHODS: Between January 1, 2008 and December 31, 2013, a total of 69 patients were enrolled in this study. They were diagnosed with lumbar spinal stenosis and underwent decompression surgery such as laminotomy in this hospital. The 3 standardized questionnaires (ODI, RMDQ, and SF 36) were given to these patients, at least 1 year after the surgery. RESULTS: ODI and SF-36 had a statistically significant (P=0.001) and moderate correlation. Small correlations were also seen between Physical Functioning (r=-0.46), Physical Role Functioning (r=-0.284), and Bodily Pain (r=-0.327) of SF-36 PCS and ODI, and between Emotional Role Functioning (r=-0.250), Social Role Functioning (r=-0.254), and Vitality (r=-0.296) of SF-36 Mental Component Score and ODI. Items in ODI for the level of pain while standing and traveling were mostly related to axial back pain, while item of lifting was related to referred buttock pain. Sleeping disturbance section in the ODI was mainly caused by radiated leg pain. In addition, RMDQ was also associated to the 3 types of pain. CONCLUSIONS: Moderate correlation was found between ODI or RMDQ as a condition-specific outcome and the SF-36, indicating overall health status. ODI was found to be a more adequate measure to evaluate axial back pain rather than referred pain or radiating pain. RMDQ was adequate to measure the health status and to evaluate the 3 types of spine pain. These 3 instruments could therefore provide the clinician with complementary information about the patient's status. PMID- 27662271 TI - Biphasic impairment of erythrocyte deformability in response to repeated, short duration exposures of supraphysiological, subhaemolytic shear stress. AB - INTRODUCTION: Despite current generation mechanical assist devices being designed to limit shear stresses and minimise damage to formed elements in blood, severe secondary complications suggestive of impaired rheological functioning are still observed. At present, the precise interactions between the magnitude-duration of shear stress exposure and the deformability of red blood cells (RBC) remain largely undescribed for repeated subhaemolytic shear stress duty-cycles of less than 15 s. Given that the time taken for blood to traverse mechanical devices (e.g., Bio Pump) typically ranges from 1.85-3.08 s, the present study examined the influence of repeated, short duration, supraphysiological shear stress exposure on RBC function. METHODS: RBC were exposed to shear stress duty-cycles of 64 Pa * 3 s or 88 Pa * 2 s, for 10 repeated bouts, in an annular Couette shearing system and ektacytometer. Laser diffractometry was used to measure RBC deformability before and after application of each duty-cycle. Free haemoglobin concentration and RBC morphology was also examined following shear exposure to determine cell viability. RESULTS: Initial exposure to shear stress duty-cycles decreased RBC deformability and increased RBC sensitivity to mechanical damage. Interestingly, the pattern of change in these variables reversed and returned to baseline values within two successive duty-cycle exposures. Significant improvements in RBC deformability were then observed by the 9th repeated exposure to 64 Pa * 3 s. CONCLUSIONS: Repeat applications of short duration supraphysiological, subhaemolytic shear stress induces a biphasic RBC deformability response that appears to progressively improve initially impaired RBC populations. PMID- 27662272 TI - The impact of Oncotype DX(r) recurrence score of paraffin-embedded core biopsy tissues in predicting response to neoadjuvant chemotherapy in women with breast cancer. AB - BACKGROUND: Oncotype DX(r) test is beneficial in predicting recurrence free survival in estrogen receptor positive (ER+) breast cancer. Ability of the assay to predict response to neoadjuvant chemotherapy (NCT) is less well-studied. OBJECTIVE: We hypothesize a positive association between the Oncotype DX(r) recurrence score (RS) and the percentage tumor response (%TR) after NCT. METHODS: Pre-therapy RS was measured on core biopsies from 60 patients with ER+, HER2- invasive breast cancer (IBC) who then received NCT. Pre-therapy tumor size was measured using imaging. %TR, partial response (PR; >50%), pathologic complete response (pCR) and breast conserving surgery (BCS) rates were measured. RESULTS: Median RS was 20 (2-69). Median %TR was 42 (0-97)%. PR was observed in 43% of patients. There was no association between %TR and pre-NCT tumor size, age, Nottingham score or nodal status (p > 0.05). No statistically significant association with %TR was seen with RS as a categorical or continuous variable (p = 0.21 and 0.7, respectively). Response to NCT improved as ER (p = 0.02) by RT PCR decreased. Lower ER expression by IHC correlated with response (p = 0.03). CONCLUSIONS: In patients with ER+ IBC receiving NCT, RS did not predict response to NCT using %TR. The benefit of the assay prior to NCT requires further study. PMID- 27662273 TI - Bioimpedance to screen for abdominal fat in patients with breast cancer treatment related lymphedema. AB - BACKGROUND: One of the dreaded complications after the treatment of breast cancer is lymphedema. Therapies used in the treatment of breast cancer such as surgery, radiotherapy, hormone therapy and chemotherapy may be adversely affected by obesity. AIM: The objective of this study was to use bioimpedance to assess abdominal fat in women with breast cancer treatment-related lymphedema and suggest this as a screening method. METHODS: Forty-five female patients with clinical diagnosis of breast cancer treatment-related lymphedema were evaluated in this quantitative cross-sectional study. A control group, composed of 38 patients with varicose veins and women attending a social support group, was matched for age and body mass index (BMI). All participants were submitted to a bioimpedance evaluation (In Body S 10), with particular attention being paid to abdominal fat and their BMI. The unpaired t -test, Fisher Exact test and Mann Whitney test were used for statistical analysis and an alpha error of 5%. RESULTS: There was no significant difference (p -value = 0.23) in the mean BMI between the study group (27.79 kg/m2) and the control group (28.80 kg/m2). The mean abdominal circumference, a measure of abdominal fat, of the women in the study group was 130.54 cm2 and for the control group it was 102.24 cm2 (p -value = 0.0037). Thus the study group had more abdominal fat (p -value = 0.0003). Moreover, on comparing obese patients in the two groups, the study group had more abdominal fat (p -value = 0.02). However, no significant difference was observed comparing non-obese patients (p -value = 0.6). The comparison of obese patients with non-obese patients in the control group identifies an association between obesity and abdominal fat (p -value < 0.04). CONCLUSION: Overweight and obese women with breast cancer treatment-related lymphedema are more likely to have increased abdominal fat than the general population with bioimpedance. PMID- 27662274 TI - Alcohol consumption and mortality after breast cancer diagnosis: The health and functioning in women study. AB - OBJECTIVE: To determine the association of prediagnostic alcohol consumption with long-term mortality from breast cancer and other causes in a cohort of women with breast cancer. METHODS: We studied a Michigan-based cohort of 939 women aged 40 84 years, who provided complete information about the type, amount and intensity of prediagnostic alcohol consumption. Associations of alcohol consumption, based on weekly volume of alcohol consumption during the year prior to breast cancer diagnosis, with mortality were evaluated in Cox proportional hazards models, with adjustment for sociodemographic factors, body mass index, smoking, comorbidity, tumor characteristics, and treatment. Differences among covariates were assessed with Pearson chi2 , Student t -tests and Wilcoxon Rank Sum tests. All statistical tests were two-sided. RESULTS: During a median follow-up of 11 years, 724 deaths occurred overall, with 303 from breast cancer. Fifty-five percent of the women were categorized as drinkers with volume of alcohol consumption ranging from 0.75 to 36.00 drinks/week. In multivariable models, a decreased risk of other-cause mortality was associated with low alcohol drinking (0.75-3.75 drinks/week; HR = 0.61, 95% CI = 0.47-0.78), moderate volume alcohol drinking (4.00-9.75 drinks/week; HR = 0.57, 95% CI = 0.39-0.85) and low frequency (0.75-3.75 drinks/week) beer and wine intake (HR = 0.69, 95% CI = 0.50-0.96 and HR = 0.68, 95% CI = 0.52-0.88 respectively). Although the risk of breast cancer-specific mortality was not statistically significantly associated with moderate (4.00-9.75 drinks/week) and high volume (10.00-36.00 drinks/week) alcohol drinking in the overall cohort (HR = 1.43, 95% CI = 95% 0.97-2.12 and HR = 1.53, 95% CI = 0.87 2.70 respectively), there was a positive association of alcohol consumption with breast cancer-specific mortality among current smokers (HR = 1.92, 95% CI = 1.03 3.57; Pinteraction = 0.04). CONCLUSION: In this prospective cohort study, regular consumption of 0.75-36.00 alcoholic drinks per week during the year prior to breast cancer diagnosis was associated with a reduction in other-cause mortality and with an increase in breast cancer-specific mortality among current smokers, after taking into account clinical and sociodemographic factors. PMID- 27662275 TI - Crystallizing galactocele: Report of a rare variation. AB - The physiological changes of the breast during pregnancy and lactation make the clinical, radiological and pathological evaluation of a breast mass challenging. Galactoceles are benign lesions containing milk, and generally occur post partum. Fine needle aspiration cytology is a simple, quick and effective technique for the diagnosis of the same during this period, and in case of galactocele the same can be both diagnostic and therapeutic.Although the cytological features of galactocele are straight forward, a few rare interesting variations can be encountered posing a diagnostic challenge to the reporting cytopathologist. We present a case of galactocele in a twenty five year old lactating female with tyrosine crystals on cytology. Milk is composed of a wide variety of proteins and minerals, leading to the formation of calcium lactate or tyrosine crystals under rare circumstances when the milieu is acidic. This is one of the rare cases of crystallizing galactoceles reported in literature till date. PMID- 27662276 TI - A new perspective on synchrotron radiation applications: Runaway electrons studies using a hard x-ray detection in tokamaks. AB - The synchrotron radiation emitted by runaway electrons in fusion plasma provides information regarding the particle momentum and pitch-angles of the runaway electron population through the strong dependence of the synchrotron spectrum on these parameters. Information about the runaway density and its spatial distribution, as well as the time evolution of the above quantities, can also be deduced. On the other hand, control of radial electric filed and suggestion of the methods to reduce plasma turbulence are important issues in confinement process and particle transport in the tokamaks. In this work, the effects of positive limiter biasing on electrical fluctuations and hard x-ray have been investigated. For this purpose, the radial and poloidal electric fields have been measured using the Langmuir probe, and hard x-ray has been measured using the Scintillator detector. The biased electric voltage was +250 V. Also, electrical fluctuations are analyzed using wavelet transform technique in the presence of positive biasing and without it. The results show that time-frequency activity of radial electric field multiplies in the presence of positive biasing while poloidal electric filed frequency intensity decreases. PMID- 27662277 TI - Prospects for application of X-ray anomalous transmission effect to monochromatization of broadband spectrum. AB - The characteristics of spectra obtained by monochromatization of a broadband spectrum using the effect of X-ray anomalous transmission (Bormann effect) have been experimentally studied. Optimization of the crystal thickness allows one to obtain the spectral band with a controlled width of DeltaE/E = 1-5 10-3 and with a contrast of more than 250 with a peak reflectivity not less than 4% in the transmitted Bormann beam. It was found that due to the wave field compression, the width of the transmitted Bormann beam decreased three times as the thickness of the crystal increased. The value of parallel displacement of the transmitted Bormann beam relative to the primary one, which depends on crystal thickness, was measured. This value was shown to be sufficient for the beams to be separated by the slit. Monitoring the transmitted Bormann beam by the shape of 2d-curves of the diffracted Laue-beam enables the precise control of characteristics of the primary source with a complex shape of angle and energy distributions of photons. PMID- 27662278 TI - Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence. AB - OBJECTIVE: To investigate possible linkages between neurodevelopmental delay and neurodevelopmental spectrum disorders and exposure to medication with effects on serotonin reuptake inhibition during pregnancy. METHODS: We systematically reviewed the epidemiological literature for studies bearing on this relationship in children born with neurodevelopmental spectrum disorder and related conditions, as well as animal studies giving serotonin reuptake inhibitors to pregnant animals and in addition reviewed the literature for proposals as to possible mechanisms that might link effects on serotonin reuptake with cognitive changes post-partum.The epidemiological studies were analysed to produce Forest plots to illustrate possible relations. RESULTS: The odds ratio of Autistic Spectrum or related Disorders in children born to women taking serotonin reuptake inhibiting antidepressants during pregnancy in case control studies was 1.95 (95% C.I. 1.63, 2.34) and in prospective cohort studies was 1.96 (95% C.I. 1.33, 2.90). CONCLUSIONS: There appears to be a link between serotonin reuptake inhibition in pregnancy and developmental delay and spectrum disorders in infancy leading to cognitive difficulties in childhood. More work needs to be done to establish more precisely the nature of the difficulties and possible mechanisms through which this link might be mediated. PMID- 27662279 TI - Study 329 continuation phase: Safety and efficacy of paroxetine and imipramine in extended treatment of adolescent major depression. AB - OBJECTIVE: This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The objectives of the continuation phase were to assess safety and relapse rates in the longer term. The objective of this publication, under the Restoring Invisible and Abandoned Trials (RIAT) initiative, was to see whether access to and analysis of the previously unpublished dataset from the continuation phase of this randomized controlled trial would have clinically relevant implications for evidence-based medicine. METHODS: The study was an eight-week double-blind randomized placebo-controlled trial with a six month continuation phase. The setting was 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. 275 adolescents with major depression were originally enrolled in Study 329, with 190 completing the eight-week acute phase. Of these, 119 patients (43%) entered the six-month continuation phase (paroxetine n = 49; imipramine n = 39; placebo n = 31), in which participants were continued on their current treatment, blinded. As per the protocol, we have looked at rates of relapse (based on Hamilton Depression Scale scores) across both acute and continuation phases, and generated a safety profile for paroxetine and imipramine compared with placebo for up to six months.ANOVA testing (generalized linear model) using a model including effects of site, treatment and site x treatment interaction was applied. Otherwise we used only descriptive statistics. RESULTS: Of patients entering the continuation phase, 15 of 49 for paroxetine (31%), 12 of 39 for imipramine (31%) and 12 of 31 for placebo (39%) completed as responders. Across the study, 25 patients on paroxetine relapsed (41% of those showing an initial response), 15 on imipramine (26%), and 10 on placebo (21%). In the continuation and taper phases combined there were 211 adverse events in the paroxetine group, 147 on imipramine and 100 on placebo. The taper phase had a higher proportion of severe adverse events per week of exposure than the acute phase, with the continuation phase having the fewest events. CONCLUSIONS: The continuation phase did not offer support for longer-term efficacy of either paroxetine or imipramine. Relapse and adverse events on both active drugs open up the risks of a prescribing cascade. The previously largely unrecognised hazards of the taper phase have implications for prescribing practice and need further exploration. PMID- 27662280 TI - Adverse event reporting and patient safety at a University Hospital: Mapping, correlating and associating events for a data-based patient risk management. AB - BACKGROUND: Reporting adverse events (AE) with a bearing on patient safety is fundamentally important to the identification and mitigation of potential clinical risks. OBJECTIVE: The aim of this study was to analyze the AE reporting systems adopted at a university hospital for the purpose of enhancing the learning potential afforded by these systems. RESEARCH DESIGN: Retrospective cohort study METHODS: Data were collected from different information flows (reports of incidents and falls, patients' claims and complaints, and cases of hospital-acquired infection [HAI]) at an university hospital. A composite risk indicator was developed to combine the data from the different flows. Spearman's nonparametric test was applied to investigate the correlation between the AE rates and a Poisson regression analysis to verify the association among characteristics of the wards and AE rates. SUBJECTS: Sixty-four wards at a University Hospital. RESULTS: There was a marked variability among wards AE rates. Correlations emerged between patients' claims with complaints and the number of incidents reported. Falls were positively associated with average length of hospital stay, number of beds, patients' mean age, and type of ward, and they were negatively associated with the average Cost Weight of the Diagnosis related group (DRG) of patients on a given ward. Claims and complaints were associated directly with the average DRG weight of a ward's patient admissions. CONCLUSIONS: This study attempted to learn something useful from an analysis of the mandatory (but often little used) data flows generated on adverse events occurring at an university hospital with a view to managing the associated clinical risk to patients. PMID- 27662281 TI - Letter to the Editor. PMID- 27662282 TI - Letter to the Editor. PMID- 27662283 TI - Letter to the Editor. PMID- 27662284 TI - A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease. AB - BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. METHODS: We used two-center resting state fMRI data of 20 AD patients (65.1+/-8.0 years), 12 bvFTD patients (64.7+/-5.4 years), and 22 control subjects (63.8+/-5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. RESULTS: At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. CONCLUSION: We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found. PMID- 27662286 TI - Cohort Study on Predictors of Need for Nursing Care in Alzheimer's Disease: An Analysis of Healthcare Data. AB - BACKGROUND: The individual and societal burden of Alzheimer's disease (AD) is substantial. Identifying relevant factors deteriorating AD and inducing need for nursing care would be of high relevance for healthcare planning. OBJECTIVE: The main objective of this study was the identification of predictors of first assignment of a level of long-term care in AD, used as an approximation for disease progression. METHODS: In a retrospective cohort study using data from a large German statutory health and long-term care insurance (SHI) company, co morbidities and drug exposure were evaluated with respect to their predictive value for disease progression (first day the amount of daily nursing care exceeded 1.5 hours). Time to disease progression was modeled using COX proportional hazard regression with stepwise selection of predictor variables. RESULTS: The risk of nursing care need increased substantially with increasing age. Number of hospitalizations and number of different drugs used were significant indicators for progression, whereas outpatient visits were associated with a reduced need for care. Gender did not indicate significant influence on progression. Malignant neoplasms of ill-defined, secondary, and unspecified sites, malnutrition, renal failure, and injuries increased the risk of need for nursing care most significantly. Among prescribed drugs, significant increased risks were associated with drugs used in diabetes, preparations for treatment of wounds and ulcers, antiseptics and disinfectants, and analgesics. CONCLUSIONS: Physical comorbidities are relevant contributors to an increase in need for nursing care. Some medical predicting conditions may be linked to cognition, while others may be directly linked to demand for care. AD patients with these comorbidities should be monitored with special attention, as they may be under an increased risk of care dependency. PMID- 27662285 TI - Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AbetaPP into Amyloidogenic Processing Pathway. AB - The cis/trans isomerization of X-Pro peptide bonds in proteins in some instances acts as a molecular switch in biological pathways. Our prior work suggests that the cis isomer of the phospho-Thr668-Pro669 motif, located in the cytoplasmic domain of the amyloid-beta protein precursor (AbetaPP), is correlated with an increase in amyloidogenic processing of AbetaPP and production of amyloid-beta (Abeta), the neurotoxic peptide fragment in Alzheimer's disease (AD). We designed a 100% cis-locked cyclic dipeptide composed of cyclized phospho-Thr-Pro (pCDP) as a mimic for this putative pathological conformation, and three phosphate-blocked derivatives (pCDP-diBzl, pCDP-Bzl, and pCDP-diPOM). Two H4 neuroglioma cell lines were established as AD cell models for use in testing these compounds: H4 AbetaPP695 for stable overexpression of wild-type AbetaPP695, and H4-BACE1 for stable overexpression of beta-site AbetaPP cleaving enzyme-1 (BACE1). The level of the secreted AbetaPP fragment resulting from BACE1 activity, sAbetaPPbeta, served as a key proxy for amyloidogenic processing, since cleavage of AbetaPP by BACE1 is a requisite first step in Abeta production. Of the compounds tested, pCDP-diBzl decreased sAbetaPPbeta levels in both cell lines, while pCDP-diPOM decreased sAbetaPPbeta levels in only H4-BACE1 cells, all with similar dose dependences and patterns of proteolytic AbetaPP fragments. Enzymatic assays showed that none of the pCDP derivatives directly inhibit BACE1 catalytic activity. These results suggest a model in which pCDP-diBzl and pCDP-diPOM act at a common point to inhibit entry of AbetaPP into the amyloidogenic AbetaPP processing pathway but through different targets, and provide important insights for the development of novel AD therapeutics. PMID- 27662288 TI - Standardized Uptake Value Ratio-Independent Evaluation of Brain Amyloidosis. AB - The assessment of in vivo18F images targeting amyloid deposition is currently carried on by visual rating with an optional quantification based on standardized uptake value ratio (SUVr) measurements. We target the difficulties of image reading and possible shortcomings of the SUVr methods by validating a new semi quantitative approach named ELBA. ELBA involves a minimal image preprocessing and does not rely on small, specific regions of interest (ROIs). It evaluates the whole brain and delivers a geometrical/intensity score to be used for ranking and dichotomic assessment. The method was applied to adniimages 18F-florbetapir images from the ADNI database. Five expert readers provided visual assessment in blind and open sessions. The longitudinal trend and the comparison to SUVr measurements were also evaluated. ELBA performed with area under the roc curve (AUC) = 0.997 versus the visual assessment. The score was significantly correlated to the SUVr values (r = 0.86, p < 10-4). The longitudinal analysis estimated a test/retest error of ?2.3%. Cohort and longitudinal analysis suggests that the ELBA method accurately ranks the brain amyloid burden. The expert readers confirmed its relevance in aiding the visual assessment in a significant number (85) of difficult cases. Despite the good performance, poor and uneven image quality constitutes the major limitation. PMID- 27662287 TI - Pathway-Specific Polygenic Risk Scores as Predictors of Amyloid-beta Deposition and Cognitive Function in a Sample at Increased Risk for Alzheimer's Disease. AB - Polygenic risk scores (PRSs) have been used to combine the effects of variants with small effects identified by genome-wide association studies. We explore the potential for using pathway-specific PRSs as predictors of early changes in Alzheimer's disease (AD)-related biomarkers and cognitive function. Participants were from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of adults who were cognitively asymptomatic at enrollment and enriched for a parental history of AD. Using genes associated with AD in the International Genomics of Alzheimer's Project's meta-analysis, we identified clusters of genes that grouped into pathways involved in amyloid-beta (Abeta) deposition and neurodegeneration: Abeta clearance, cholesterol metabolism, and immune response. Weighted pathway-specific and overall PRSs were developed and compared to APOE alone. Mixed models were used to assess whether each PRS was associated with cognition in 1,200 individuals, cerebral Abeta deposition measured using amyloid ligand (Pittsburgh compound B) positron emission imaging in 168 individuals, and cerebrospinal fluid Abeta deposition, neurodegeneration, and tau pathology in 111 individuals, with replication performed in an independent sample. We found that PRSs including APOE appeared to be driven by the inclusion of APOE, suggesting that the pathway-specific PRSs used here were not more predictive than an overall PRS or APOE alone. However, pathway-specific PRSs could prove to be useful as more knowledge is gained on the genetic variants involved in specific biological pathways of AD. PMID- 27662289 TI - Occupational Attainment as Risk Factor for Progression from Mild Cognitive Impairment to Alzheimer's Disease: A CREDOS Study. AB - High occupational attainment has been known as a marker of cognitive reserve. Previous studies in the general population have shown that high occupational attainment is associated with reduced risk of Alzheimer's disease (AD). However, few studies have assessed the effect of occupational attainment on the clinical course of mild cognitive impairment (MCI). In this study, we evaluated whether individuals with high occupational attainment show more frequent progression from MCI to AD. Participants (n = 961) with MCI were recruited from a nationwide, hospital-based multi-center cohort, and were followed for up to 60 months (median: 17.64, interquartile range [12.36, 29.28]). We used Cox regression for competing risks to analyze the effect of occupational attainment on development of AD, treating dementia other than AD as a competing risk. Among the 961 individuals with MCI, a total of 280 (29.1%) converted to dementia during the follow-up period. The risk of progression to AD was higher in the individuals with high occupational attainment after controlling for potential confounders (hazard ratio = 1.83, 95% confidence interval = 1.25-2.69, p = 0.002). High occupational attainment in individuals with MCI is an independent risk factor for higher progression rate of MCI to AD. This result suggests that the protective effect of high occupational attainment against cognitive decline disappears in the MCI stage, and that careful assessment of occupational history can yield important clinical information for prognosis in individuals with MCI. PMID- 27662290 TI - Cognitive-Enhancing Effects of a Polyphenols-Rich Extract from Fruits without Changes in Neuropathology in an Animal Model of Alzheimer's Disease. AB - No effective preventive treatment is available for age-related cognitive decline and Alzheimer's disease (AD). Epidemiological studies indicate that a diet rich in fruit is associated with cognitive improvement. It was thus proposed that high polyphenol concentrations found in berries can prevent cognitive impairment associated with aging and AD. Therefore, the Neurophenols project aimed at investigating the effects of a polyphenolic extract from blueberries and grapes (PEBG) in the triple-transgenic (3xTg-AD) mouse model of AD, which develops AD neuropathological markers, including amyloid-beta plaques and neurofibrillary tangles, leading to memory deficits. In this study, 12-month-old 3xTg-AD and NonTg mice were fed a diet supplemented with standardized PEBG (500 or 2500 mg/kg) for 4 months (n = 15-20/group). A cognitive evaluation with the novel object recognition test was performed at 15 months of age and mice were sacrificed at 16 months of age. We observed that PEBG supplementation with doses of 500 or 2500 mg/kg prevented the decrease in novel object recognition observed in both 15-month-old 3xTg-AD mice and NonTg mice fed a control diet. Although PEBG treatment did not reduce Abeta and tau pathologies, it prevented the decrease in mature BDNF observed in 16-month-old 3xTg-AD mice. Finally, plasma concentrations of phenolic metabolites, such as dihydroxyphenyl valerolactone, a microbial metabolite of epicatechin, positively correlated with memory performances in supplemented mice. The improvement in object recognition observed in 3xTg-AD mice after PEBG administration supports the consumption of polyphenols rich extracts to prevent memory impairment associated with age-related disease, without significant effects on classical AD neuropathology. PMID- 27662291 TI - Spatial Patterns of Longitudinal Gray Matter Change as Predictors of Concurrent Cognitive Decline in Amyloid Positive Healthy Subjects. AB - A substantial proportion of cognitively healthy elders (HC) show abnormally high amyloid-beta (Abeta) deposition, a major pathology of Alzheimer's disease (AD). These subjects are at increased risk of Alzheimer's disease (AD) dementia, and biomarkers are needed to predict their cognitive deterioration. Here we used relevance vector regression (RVR), a pattern-recognition method, to predict concurrent cognitive decline on the basis of longitudinal gray matter (GM) changes, within two a priori, meta-analytically defined functional networks subserving episodic memory and executive function. Ninety-six HC subjects were assessed annually for three years with structural MRI and cognitive tests within the Alzheimer's Disease Neuroimaging Initiative. Presence of abnormal biomarker values of Abeta (Abeta+) were determined with cerebrospinal fluid and amyloid-PET (HC-Abeta+, n=30; with n=66 for normal HC-Abeta-). Using leave-one-out cross validation, we found that in HC-Abeta+ patterns of GM changes within both networks predicted decline in episodic memory (r=0.61, p<0.001; r=0.40, p=0.03), but not executive function. In HC-Abeta-, GM changes within the executive function network predicted decline in executive function (r=0.44, p<0.001). Previously established region-of-interest (ROI)-based predictors such as changes in hippocampal volume, within an AD-signature multi-ROI, or total GM volume were not predictive of cognitive decline in any group or cognitive domain. RVR analyses unrestricted to the a priori networks yielded compatible results with the restricted case. In conclusion, RVR-derived patterns of subtle cortical GM changes are biomarker candidates of concurrent cognitive decline in aging and subjects at risk for AD. PMID- 27662293 TI - Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes: A Pilot Study. AB - BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous disease both at the clinical, genetic, and pathobiological level. The underlying pathological spectrum (termed FTLD, frontotemporal lobar degeneration) is in most cases defined by accumulation of either tau (FTLD-tau) or TDP-43 proteins (FTLD-TDP). Biomarkers to differentiate these subtypes are not yet available, whereas these are essential requirements to study the natural course of disease and for homogeneous inclusion of patients in clinical studies. OBJECTIVE: To study if a combination of total (t-) and phosphorylated (p-)tau, and t-TDP-43 and p-TDP-43 proteins in cerebrospinal fluid (CSF) is suitable to discriminate FTLD-tau and FTLD-TDP subtypes. METHODS: We developed immunoassays for the quantification of t TDP-43 and p-TDP-43 proteins and used commercially available assays for the quantification of t-tau and p-tau proteins. We quantified these proteins in ventricular CSF samples from neuropathologically defined FTLD-tau and FTLD-TDP cases to study the reflection of underlying brain pathology in CSF composition, and in lumbar CSF samples from FTLD-tau and FTLD-TDP patients to study the diagnostic potential of CSF biomarkers. RESULTS: In ventricular CSF, t-TDP-43 and t-tau levels, when combined into one model, were significantly different between neuropathologically-defined FTLD-tau and FTLD-TDP cases. In a pilot study using lumbar CSF, the p-tau/t-tau ratio, but not t-TDP-43 levels, were significantly different between FTLD-TDP and FTLD-tau patients. CONCLUSION: We conclude that with current available methods, CSF tau, rather than TDP-43 proteins, may have diagnostic value in the differentiation of FTLD patients with either tau or TDP 43 pathology. PMID- 27662292 TI - Aberrant Co-localization of Synaptic Proteins Promoted by Alzheimer's Disease Amyloid-beta Peptides: Protective Effect of Human Serum Albumin. AB - Amyloid-beta (Abeta), Abeta40, Abeta42, and, recently, Abeta25-35 have been directly implicated in the pathogenesis of Alzheimer's disease. We have studied the effects of Abeta on neuronal death, reactive oxygen species (ROS) production, and synaptic assembling in neurons in primary culture. Abeta25-35, Abeta40, and Abeta42 significantly decreased neuronal viability, although Abeta25-35 showed a higher effect. Abeta25-35 showed a more penetrating ability to reach mitochondria while Abeta40 did not enter the neuronal cytosol and Abeta42 was scarcely internalized. We did not observe a direct correlation between ROS production and cell death because both Abeta40 and Abeta42 decreased neuronal viability but Abeta40 did not change ROS production. Rather, ROS production seems to correlate with the penetrating ability of each Abeta. No significant differences were found between Abeta40 and Abeta42 regarding the extent of the deleterious effects of both peptides on neuronal viability or synaptophysin expression. However, Abeta40 elicited a clear delocalization of PSD-95 and synaptotagmin from prospective synapsis to the neuronal soma, suggesting the occurrence of a crucial effect of Abeta40 on synaptic disassembling. The formation of Abeta40- or Abeta42-serum albumin complexes avoided the effects of these peptides on neuronal viability, synaptophysin expression, and PSD-95/synaptotagmin disarrangement suggesting that sequestration of Abeta by albumin prevents deleterious effects of these peptides. We can conclude that Abeta borne by albumin can be safely transported through body fluids, a fact that may be compulsory for Abeta disposal by peripheral tissues. PMID- 27662294 TI - Increased PCSK9 Cerebrospinal Fluid Concentrations in Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) has been associated with dysregulation of brain cholesterol trafficking and abnormal production of apolipoprotein E isoform 4 (apoE4). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein present in serum and cerebrospinal fluid (CSF) degrading the low-density lipoprotein receptor (LDLr) and other apoE-binding receptors involved in neuron cholesterol uptake. The role of PCSK9 in AD is controversial. OBJECTIVE: We compared PCSK9 levels in CSF of AD patients and non-AD controls and looked at correlations with CSF total apoE and apoE4. METHODS: CSF from AD (n = 30) and from age and sex-matched non-AD patients (n = 30) was collected by lumbar puncture for routine diagnosis. CSF PCSK9, total apoE, and apoE4 levels were measured by ELISA. AD patients showed the typical CSF neurobiomarker pattern (decreased Abeta42 and increased tau and phospho-tau) and impaired cognitive performances, as indicated by the scores of the Mini-Mental State Examination test. RESULTS: PCSK9 levels in CSF were higher in AD than in non-AD subjects (+1.45 fold; p = 0.0049). CSF total apoE concentrations did not differ between the two groups, while apoE4 levels were higher in AD subjects (+3.34 fold; p = 0.0068). Considering all samples, a significant positive correlation was found between PCSK9 and apoE4 (r = 0.4409; p = 0.0006). PCSK9 levels were higher in APOE E4 carriers, reaching statistical significance in the AD group (+1.45 fold; p = 0.0454). CONCLUSION: These results report for the first time an alteration of CSF PCSK9 levels in AD and suggest a pathophysiological link between PCSK9, apoE4, and AD. PMID- 27662295 TI - Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization. AB - BACKGROUND: Virtually nothing is known about a potential diagnostic role of non phospho-epitopes of Tau (Non-P-Tau) in cerebrospinal fluid (CSF). OBJECTIVE: To establish and analytically and clinically characterize the first assay capable to measure concentrations of Non-P-Tau in human CSF. METHODS: An antibody (1G2) was developed that selectively binds to the Tau molecule non-phosphorylated at the positions T175 and T181, and was used in establishing a sandwich ELISA capable to measure Non-P-Tau in human CSF, following analytical and clinical validation of the method. RESULTS: The 1G2 antibody shows decreasing reactivity to tau peptides containing phosphorylation mainly at positions T175 and T181. Detection limit of the assay is 25 pg/ml; the coefficients of variation (CVs) of the optical densities of the repeated standard curves were between 3.6-15.9%. Median intra assay imprecision of double measurements was 4.8%; inter-assay imprecision was in the range of 11.2% - 15.3%. Non-P-Tau concentrations are stable in the CSF samples sent to distinct laboratories under ambient temperature; inter-laboratory variation was approximately 30%. The Non-P-Tau CSF concentrations were highly significantly increased in patients with Alzheimer's disease in stage of mild cognitive impairment or dementia (AD/MCI, n = 58, 109.2+/-32.0 pg/mL) compared to the non-demented Controls (n = 42, 62.1+/-9.3 pg/mL, p < 0.001). At the cut-off of 78.3 pg/mL, the sensitivity and the specificity were 94.8% and 97.6%, respectively. CONCLUSION: For the first time, an assay is reported to reliably measure concentrations of non-phosphorylated Tau in human CSF. PMID- 27662296 TI - Preclinical Amyloid-beta and Axonal Degeneration Pathology in Delirium. AB - BACKGROUND: The clinical relevance of brain beta-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. OBJECTIVE: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-beta 1-42 (Abeta42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. METHODS: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Abeta42, T-tau, and P-tau were analyzed. RESULTS: In patients without dementia, we found lower CSF Abeta42 levels (median, 310 ng/L versus 489 ng/L, p = 0.006), higher T-tau levels (median, 505 ng/L versus 351 ng/L, p = 0.02), but no change in P-tau in patients who developed delirium (n = 16) compared to those who remained lucid (n = 49). Delirious patients also had lower ratios of Abeta42 to T tau (p < 0.001) and P-tau (p = 0.001) relative to those without delirium. CSF Abeta42 and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n = 54) and without delirium (n = 10). CONCLUSION: The reduction in CSF Abeta42, indicating beta-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology. PMID- 27662297 TI - Increased Serum miR-206 Level Predicts Conversion from Amnestic Mild Cognitive Impairment to Alzheimer's Disease: A 5-Year Follow-up Study. AB - Evidence suggests that individuals with amnestic mild cognitive impairment (aMCI) tend to progress to probable Alzheimer's disease (AD) with aging. This study was performed to examine whether circulating miRNAs could be potential predictors for the progression of aMCI to AD. A total of 458 patients with aMCI were included in this study, and the clinical data were collected at two time points: the baseline and the follow-up assessment. These aMCI patients were classified into two groups after 5 years: aMCI-stable group (n = 330) and AD-conversion group (n = 128). The expression of miR-206 and miR-132 and the levels of BDNF and SIRT1 in serum were detected using a quantitative real-time RT-PCR (qPCR) and the ELISA method, respectively. Kaplan-Meier method (Log-rank test) was used for univariate survival analysis. Cox proportional hazard model was used to estimate the prognostic value of miRNAs in conversion from aMCI to AD. At the baseline, serum levels of miR-206 in aMCI-AD group were significantly elevated compared to aMCI aMCI group and the same trend was found at 5-year follow-up time point as well. There were no significant differences in serum levels of miR-132 between the conversion and non-conversion group at both time points. Kaplan-Meier analysis showed significant correlation between AD conversion and higher serum levels of miR-206 for aMCI patients (HR = 3.60, 95% CI: 2.51- 5.36, p < 0.001). Multivariate Cox regression analysis revealed that serum miR-206 and its target BDNF were significant independent predictors for AD conversion (HR = 4.22, p < 0.001). These results suggested that increased serum miR-206 level might be a potential predictor of conversion from aMCI to AD. PMID- 27662298 TI - Copy Number Variants in Alzheimer's Disease. AB - Alzheimer's disease (AD) is a devastating disease mainly afflicting elderly people, characterized by decreased cognition, loss of memory, and eventually death. Although risk and deterministic genes are known, major genetics research programs are underway to gain further insights into the inheritance of AD. In the last years, in particular, new developments in genome-wide scanning methodologies have enabled the association of a number of previously uncharacterized copy number variants (CNVs, gain or loss of DNA) in AD. Because of the exceedingly large number of studies performed, it has become difficult for geneticists as well as clinicians to systematically follow, evaluate, and interpret the growing number of (sometime conflicting) CNVs implicated in AD. In this review, after a brief introduction of this type of structural variation, and a description of available databases, computational analyses, and technologies involved, we provide a systematic review of all published data showing statistical and scientific significance of pathogenic CNVs and discuss the role they might play in AD. PMID- 27662299 TI - White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non Demented Older Individuals with Abnormal Amyloid-beta. AB - Cerebral small vessel disease (cSVD) and amyloid-beta (Abeta) deposition often co exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Abeta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Abeta pathology was assessed as cerebrospinal fluid-derived Abeta1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Abeta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Abeta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Abeta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Abeta42 levels, but not in individuals with normal CSF Abeta42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Abeta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present. PMID- 27662300 TI - An Intranasal Formulation of Erythropoietin (Neuro-EPO) Prevents Memory Deficits and Amyloid Toxicity in the APPSwe Transgenic Mouse Model of Alzheimer's Disease. AB - Erythropoietin (EPO) is a cytokine known to have effective cytoprotective action in the brain, particularly in ischemic, traumatic, inflammatory, and neurodegenerative conditions. We previously reported the neuroprotective effect of a low sialic form of EPO, Neuro-EPO, applied intranasally in rodent models of stroke or cerebellar ataxia and in a non-transgenic mouse model of Alzheimer's disease (AD). Here we analyzed the protective effect of Neuro-EPO in APPSwe mice, a reference transgenic mouse model of AD. Mice were administered 3 times a day, 3 days in the week with Neuro-EPO (125, 250 MUg/kg) intranasally, between 12 and 14 months of age. Motor responses, general activity, and memory responses were analyzed during and after treatment. The deficits in spontaneous alternation, place learning in the water-maze, and novel object recognition observed in APPSwe mice were alleviated by the low dose of Neuro-EPO. Oxidative stress, neuroinflammation, trophic factor levels, and a synaptic marker were analyzed in the hippocampus or cortex of the animals. The increases in lipid peroxidation or in GFAP and Iba-1 contents in APPSwe mice were significantly reduced after Neuro EPO. Activation of intrinsic and extrinsic apoptotic pathways was analyzed. The increases in Bax/Bcl-2 ratio, TNFalpha, or Fas ligand levels observed in APPSwe mice were reduced by Neuro-EPO. Finally, immunohistochemical and ELISA analyses of Abeta1-42 levels in the APPSwe mouse cortex and hippocampus showed a marked reduction in Abeta deposits and in soluble and insoluble Abeta1-42 forms. This study therefore confirmed the neuroprotective activity of EPO, particularly for an intranasally deliverable formulation, devoid of erythropoietic side effects, in a transgenic mouse model of AD. Neuro-EPO alleviated memory alterations, oxidative stress, neuroinflammation, apoptosis induction, and amyloid load in 14 month-old APPSwe mice. PMID- 27662302 TI - How Different are Quality of Life Ratings for People with Dementia Reported by Their Family Caregivers from Those Reported by the Patients Themselves? AB - BACKGROUND: Measurements of patient quality of life (QoL) play a major role in the management of dementia. OBJECTIVE: We investigated the self-proxy discrepancy of QoL ratings in the elderly and the impact of dementia severity on the discrepancy. METHODS: QoL of 718 patients with dementia and 651 non-demented elderly were rated by themselves and their caregivers (CG) using the Quality of Life-Alzheimer's Disease (QoL-AD). The impact of the rater on the total and item scores of QoL-AD was analyzed using repeated measures ANOVA and differential response patterns between self and proxy were analyzed using differential item functioning (DIF) analysis. RESULTS: Self-rated scores were higher than CG-rated scores in all diagnostic groups. The interaction between rater and diagnostic group was significant in total QoL-AD score and 5 item scores ('memory', 'marriage', 'chores around the house', 'do things for fun', and 'life as a whole'). The strength of the DIF increased with advancing dementia in these items. CONCLUSION: Self-proxy rating discrepancy of QoL was influenced by the presence and severity of dementia only in five items. PMID- 27662303 TI - Tau Proteins Cross the Blood-Brain Barrier. AB - Tauopathies are a hallmark of many neurodegenerative diseases, including Alzheimer's disease and traumatic brain injuries. It has been demonstrated that amyloid-beta peptides, alpha-synuclein, and prion proteins cross the blood-brain barrier (BBB), contributing to their abilities to induce disease. Very little is known about whether tau proteins can cross the BBB. Here we systematically characterized several key forms of tau proteins to cross the BBB, including Tau 441 (2N4R), Tau-410 (2N3R), truncated tau 151-391 (0N4R), and truncated tau 121 227. All of these tau proteins crossed the BBB readily and bidirectonally; however, only Tau-410 had a saturable component to its influx. The tau proteins also entered the blood after their injection into the brain, with Tau 121-227 having the slowest exit from brain. The tau proteins varied in regards to their enzymatic stability in brain and blood and in their peripheral pharmacokinetics. These results show that blood-borne tau proteins could contribute to brain tauopathies. The result also suggest that the CNS can contribute to blood levels of tau, raising the possibility that, as suggested for other misfolded proteins, blood levels of tau proteins could be used as a biomarker of CNS disease. PMID- 27662304 TI - Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease. AB - The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges of the major paradigm in the field, the amyloid hypothesis, are sharply formulated. These challenges together show that new approaches are necessary that address data heterogeneity, increase focus on the proteome level, use available human patient data more actively, account for the aging phenotype as a background model of the disease, unify our understanding of the interplay between genetic and non-genetic risk factors, and combine into one framework both the familial and sporadic forms of the disease. PMID- 27662301 TI - The Role of Cerebrovascular Disease on Cognitive and Functional Status and Psychosis in Severe Alzheimer's Disease. AB - BACKGROUND: The pathophysiology behind psychosis in patients with Alzheimer's disease (AD) remains unknown. Recently, vascular risk factors have been recognized as important modifiers of the clinical presentation of AD. OBJECTIVE: The purpose of our study is to investigate the mechanism through which vascular risk factors mediate psychosis and whether or not it involves cerebrovascular lesions. METHODS: Data was provided by the National Alzheimer's Coordinating Centre. The Uniform Data Set was used to collect information on subject-reported history of vascular risk factors, clinician-reported state of cognitive performance, and presence of psychosis based on the Neuropsychiatric Inventory Questionnaire (NPI-Q). The Neuropathology Data Set was used to evaluate the presence of vascular lesions and the severity of AD pathology. Subjects with high probability of AD based on the NIA/AA Reagan criteria were included in the analysis. RESULTS: We identified 1,459 patients with high probability of AD and corresponding NPI-Q scores. We confirmed the association between hypertension and diabetes on psychosis, specifically in delusions and the co-occurrence of delusions and hallucinations. Furthermore, the presence of white matter rarefaction based on pathological evaluation was associated with hallucinations. A history of vascular risk factors was positively associated with vascular lesions. However, vascular lesions in the presence of vascular risk factors did not increase the likelihood of psychosis. Furthermore, vascular lesions were not associated with greater cognitive or functional impairments in this group with severe AD pathology. CONCLUSION: Vascular risk factors and vascular lesions are independently associated with psychosis in patients with severe AD. However, vascular lesions are not the mechanism through which vascular risk factors mediate psychosis. PMID- 27662305 TI - Altered Sphingolipid Balance in Capillary Cerebral Amyloid Angiopathy. AB - BACKGROUND: The majority of patients with Alzheimer's disease (AD) exhibit amyloid-beta (Abeta) deposits at the brain vasculature, a process referred to as cerebral amyloid angiopathy (CAA). In over 51% of AD cases, Abeta also accumulates in cortical capillaries, which is termed capillary CAA (capCAA). It has been postulated that the presence of capCAA in AD is a specific subtype of AD, although underlying mechanisms are not yet fully understood. Sphingolipids (SLs) are implicated in neurodegenerative disorders, including AD. However, to date it remains unknown whether alterations in the SL pathway are involved in capCAA pathogenesis and if these differ from AD. OBJECTIVE: To determine whether AD cases with capCAA have an altered SL profile compared to AD cases without capCAA. METHODS: Immunohistochemistry was performed to assess the expression and localization of ceramide, acid sphingomyelinase (ASM), and sphingosine-1 phosphate receptors (S1P1, S1P3). In addition, we determined the concentrations of S1P as well as different chain-lengths of ceramides using HPLC-MS/MS. RESULTS: Immunohistochemical analysis revealed an altered expression of ceramide, ASM, and S1P receptors by reactive astrocytes and microglial cells specifically associated with capCAA. Moreover, a shift in the balance of ceramides with different chain lengths and S1P content is observed in capCAA. CONCLUSION: Here we provide evidence of a deregulated SL balance in capCAA. The increased levels of ASM and ceramide in activated glia cells suggest that the SL pathway is involved in the neuroinflammatory response in capCAA pathogenesis. Future research is needed to elucidate the role of S1P in capCAA. PMID- 27662306 TI - Sphingolipid-Enriched Extracellular Vesicles and Alzheimer's Disease: A Decade of Research. AB - Extracellular vesicles (EVs), particularly exosomes, have emerged in the last 10 years as a new player in the progression of Alzheimer's disease (AD) with high potential for being useful as a diagnostic and treatment tool. Exosomes and other EVs are enriched with the sphingolipid ceramide as well as other more complex glycosphingolipids such as gangliosides. At least a subpopulation of exosomes requires neutral sphingomyelinase activity for their biogenesis and secretion. As ceramide is often elevated in AD, exosome secretion may be affected as well. Here, we review the available data showing that exosomes regulate the aggregation and clearance of amyloid-beta (Abeta) and discuss the differences in data from laboratories regarding Abeta binding, induction of aggregation, and glial clearance. We also summarize available data on the role of exosomes in extracellular tau propagation, AD-related exosomal mRNA/miRNA cargo, and the use of exosomes as biomarker and gene therapy vehicles for diagnosis and potential treatment. PMID- 27662308 TI - Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer's Disease. AB - Previously, DJ-1 modulator UCP0054278/comp-B was identified by virtual screening, where comp-B interacts with DJ-1 to produce antioxidant and neuroprotective responses in Parkinson's disease models. However, the effect of comp-B in an in vivo Alzheimer's disease (AD) model is yet undetermined. Thus, we examined the effect of comp-B on spatial learning, memory, and amyloid-beta (Abeta) clearance in a transgenic mouse model of AD. We found that comp-B resolved the cognitive deficits, reduced insoluble Abeta42 levels, and prevented the degeneration of synaptic functions, thereby suggesting that comp-B may become a major compound for AD treatment. PMID- 27662307 TI - Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: A View of the Regulatory Science Qualification Landscape from the Coalition Against Major Diseases CSF Biomarker Team. AB - Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development. PMID- 27662309 TI - Prediction of Incipient Alzheimer's Disease Dementia in Patients with Mild Cognitive Impairment. AB - BACKGROUND: Mild cognitive impairment (MCI) is a transitional stage from normal aging to Alzheimer's disease (AD) dementia. It is extremely important to develop criteria that can be used to separate the MCI subjects at imminent risk of conversion to Alzheimer-type dementia from those who would remain stable. We have developed an automatic algorithm for computing a novel measure of hippocampal volumetric integrity (HVI) from structural MRI scans that may be useful for this purpose. OBJECTIVE: To determine the utility of HVI in classification between stable and progressive MCI patients using the Random Forest classification algorithm. METHODS: We used a 16-dimensional feature space including bilateral HVI obtained from baseline and one-year follow-up structural MRI, cognitive tests, and genetic and demographic information to train a Random Forest classifier in a sample of 164 MCI subjects categorized into two groups [progressive (n = 86) or stable (n = 78)] based on future conversion (or lack thereof) of their diagnosis to probable AD. RESULTS: The overall accuracy of classification was estimated to be 82.3% (86.0% sensitivity, 78.2% specificity). The accuracy in women (89.1%) was considerably higher than that in men (78.9%). The prediction accuracy achieved in women is the highest reported in any previous application of machine learning to AD diagnosis in MCI. CONCLUSION: The method presented in this paper can be used to separate stable MCI patients from those who are at early stages of AD dementia with high accuracy. There may be stronger indicators of imminent AD dementia in women with MCI as compared to men. PMID- 27662310 TI - Cognitive and Neuroanatomical Correlates in Early Versus Late Onset Parkinson's Disease Dementia. AB - BACKGROUND: Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset. OBJECTIVES: The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset. METHODS: A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance. RESULTS: EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044). CONCLUSIONS: Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD. PMID- 27662312 TI - Stress-Induced Synaptic Dysfunction and Neurotransmitter Release in Alzheimer's Disease: Can Neurotransmitters and Neuromodulators be Potential Therapeutic Targets? AB - The communication between neurons at synaptic junctions is an intriguing process that monitors the transmission of various electro-chemical signals in the central nervous system. Albeit any aberration in the mechanisms associated with transmission of these signals leads to loss of synaptic contacts in both the neocortex and hippocampus thereby causing insidious cognitive decline and memory dysfunction. Compelling evidence suggests that soluble amyloid-beta (Abeta) and hyperphosphorylated tau serve as toxins in the dysfunction of synaptic plasticity and aberrant neurotransmitter (NT) release at synapses consequently causing a cognitive decline in Alzheimer's disease (AD). Further, an imbalance between excitatory and inhibitory neurotransmission systems induced by impaired redox signaling and altered mitochondrial integrity is also amenable for such abnormalities. Defective NT release at the synaptic junction causes several detrimental effects associated with altered activity of synaptic proteins, transcription factors, Ca2+ homeostasis, and other molecules critical for neuronal plasticity. These detrimental effects further disrupt the normal homeostasis of neuronal cells and thereby causing synaptic loss. Moreover, the precise mechanistic role played by impaired NTs and neuromodulators (NMs) and altered redox signaling in synaptic dysfunction remains mysterious, and their possible interlink still needs to be investigated. Therefore, this review elucidates the intricate role played by both defective NTs/NMs and altered redox signaling in synaptopathy. Further, the involvement of numerous pharmacological approaches to compensate neurotransmission imbalance has also been discussed, which may be considered as a potential therapeutic approach in synaptopathy associated with AD. PMID- 27662313 TI - Neuroprotective Effect of TREM-2 in Aging and Alzheimer's Disease Model. AB - Neuroinflammation and activation of innate immunity are early events in neurodegenerative diseases including Alzheimer's disease (AD). Recently, a rare mutation in the gene Triggering receptor expressed on myeloid cells 2 (TREM2) has been associated with a substantial increase in the risk of developing late onset AD. To uncover the molecular mechanisms underlying this association, we investigated the RNA and protein expression of TREM2 in APP/PS1 transgenic mice. Our findings suggest that TREM2 not only plays a critical role in inflammation, but is also involved in neuronal cell survival and in neurogenesis. We have shown that TREM2 is a soluble protein transported by macrophages through ventricle walls and choroid plexus, and then enters the brain parenchyma via radial glial cells. TREM2 protein is essential for neuroplasticity and myelination. During the late stages of life, a lack of TREM2 protein may accelerate aging processes and neuronal cell loss and reduce microglial activity, ultimately leading to neuroinflammation. As inflammation plays a major role in neurodegenerative diseases, a lack of TREM2 could be a missing link between immunomodulation and neuroprotection. PMID- 27662311 TI - How Studies of the Serotonin System in Macaque Models of Menopause Relate to Alzheimer's Disease1. AB - Serotonin plays a key role in mood or affect, and dysfunction of the serotonin system has been linked to depression in humans and animal models. Depression appears prior to or coincident with overt symptoms of Alzheimer's disease (AD) in about 50% of patients, and some experts consider it a risk factor for the development of AD. In addition, AD is more prevalent in women, who also show increased incidence of depression. Indeed, it has been proposed that mechanisms underlying depression overlap the mechanisms thought to hasten AD. Women undergo ovarian failure and cessation of ovarian steroid production in middle age and the postmenopausal period correlates with an increase in the onset of depression and AD. This laboratory has examined the many actions of ovarian steroids in the serotonin system of non-human primates using a rhesus macaque model of surgical menopause with short or long-term estradiol (E) or estradiol plus progesterone (E+P) replacement therapy. In this mini-review, we present a brief synopsis of the relevant literature concerning AD, depression, and serotonin. We also present some of our data on serotonin neuron viability, the involvement of the caspase independent pathway, and apoptosis-inducing factor in serotonin-neuron viability, as well as gene expression related to neurodegeneration and neuron viability in serotonin neurons from adult and aged surgical menopausal macaques. We show that ovarian steroids, particularly E, are crucial for serotonin neuron function and health. In the absence of E, serotonin neurons are endangered and deteriorating toward apoptosis. The possibility that this scenario may proceed or accompany AD in postmenopausal women seems likely. PMID- 27662316 TI - Social Cognition in the Frontal Variant of Alzheimer's Disease: A Case Study. AB - Although frontal presentations of Alzheimer's disease (fv-AD) have already been described in the literature, we still know little about patients' social cognitive abilities, especially their theory of mind (ToM). We report the case of FT, a 61-year-old woman who was diagnosed with fv-AD. Two assessments of social cognition, using a false-belief task, the Reading the Mind in the Eyes test, and a task probing knowledge of social norms, were performed one year apart. FT exhibited cognitive ToM and social knowledge deficits from the onset. Affective ToM was initially preserved, but deteriorated as the disease progressed. PMID- 27662315 TI - The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia. AB - BACKGROUND AND OBJECTIVE: Primary progressive aphasia (PPA) is a clinical syndrome due to different neurodegenerative conditions in which an accurate early diagnosis needs to be supported by a reliable diagnostic tool at the individual level. In this study, we investigated in PPA the FDG-PET brain metabolic patterns at the single-subject level, in order to assess the case-to-case variability and its relationship with clinical-neuropsychological findings. MATERIAL AND METHODS: 55 patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17 logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m PPA) were included. Clinical-neuropsychological information and FDG-PET data were acquired at baseline. A follow-up of 27.4+/-12.55 months evaluated the clinical progression. Brain metabolism was analyzed using an optimized and validated voxel based SPM method at the single-subject level. RESULTS: FDG-PET voxel-wise metabolic assessment revealed specific metabolic signatures characterizing each PPA variant at the individual level, reflecting the underlying neurodegeneration in language networks. Notably, additional dysfunctional patterns predicted clinical progression to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern characterized by involvement of parietal, subcortical and brainstem structures predicted progression to a corticobasal degeneration syndrome or to progressive supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer's disease and frontotemporal dementia at the follow-up presented with extended bilateral patterns at baseline. DISCUSSION: Our results indicate that FDG-PET voxel-wise imaging is a valid biomarker for the early differential diagnosis of PPAs and for the prediction of progression to specific dementia condition. This study supports the use of FDG-PET imaging quantitative assessment in clinical settings for a better characterization of PPA individuals and prognostic definition of possible endo-phenotypes. PMID- 27662314 TI - Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer's Disease. AB - BACKGROUND: The immune system is increasingly mentioned as a potential target for Alzheimer's disease (AD) treatment. OBJECTIVE: In the present pilot study, the effect of (neuro)inflammation on amyloidopathy was investigated in the marmoset monkey, which has potential as an AD animal model due to its natural cerebral amyloidosis similar to humans. METHODS: Six adult/aged marmosets (Callithrix jacchus) were intracranial injected with amyloid-beta (Abeta) fibrils at three cortical locations in the right hemisphere. Additionally, in half of the monkeys, lipopolysaccharide (LPS) was co-injected with the Abeta fibrils and injected in the other hemisphere without Abeta fibrils. The other three monkeys received phosphate buffered saline instead of LPS, as a control for the inflammatory state. The effect of inflammation on amyloidopathy was also investigated in an additional monkey that suffered from chronic inflammatory wasting syndrome. Mirror histology sections were analyzed to assess amyloidopathy and immune reaction, and peripheral blood for AD biomarker expression. RESULTS: All LPS injected monkeys showed an early AD immune blood cell expression profile on CD95 and CD45RA. Two out of three monkeys injected with Abeta and LPS and the additional monkey, suffering from chronic inflammation, developed plaques. None of the controls, injected with Abeta only, developed any plaques. CONCLUSION: This study shows the importance of immune modulation on the susceptibility for amyloidosis, a hallmark of AD, which offers new perspectives for disease modifying approaches in AD. PMID- 27662317 TI - Comparison of Gait Parameters for Predicting Cognitive Decline: The Mayo Clinic Study of Aging. AB - BACKGROUND: Previous studies reported that slower gait speed might predict cognitive impairment and dementing illnesses, supporting the role of gait speed as a possible subclinical marker of cognitive impairment. However, the predictive value of other gait parameters for cognitive decline is unclear. OBJECTIVE: To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample. METHODS: The analysis included 3,426 cognitively normal participants enrolled in the Mayo Clinic Study of Aging. At baseline and every 15 months (mean follow-up = 1.93 years), participants had a study coordinator evaluation, neurological examination, and a neuropsychological assessment using nine tests that covered four domains. Gait parameters were assessed with the GAITRite(r) instrument. General linear mixed effects models were used to compute the annualized rate of change in cognitive domain z-scores, controlling for age, sex, education, depression, comorbidities, body mass index, APOE E4 allele, and visit number, and excluding individuals with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, and normal pressure hydrocephalus. RESULTS: Spatial (stride length), temporal (ambulatory time, gait speed, step count, cadence, double support time), and spatiotemporal (cadence) gait parameters, and greater intraindividual variability in stride length, swing time, and stance time were associated with a significant decline in global cognition and in specific domains including memory, executive function, visuospatial, and language. CONCLUSIONS: Spatial, temporal, and spatiotemporal measures of gait and greater variability of gait parameters were associated with and predictive of both global- and domain-specific cognitive decline. PMID- 27662319 TI - Network-Based Substrate of Cognitive Reserve in Alzheimer's Disease. AB - Cognitive reserve (CR) is known to modulate the clinical features of Alzheimer's disease (AD). This concept may be critical for the development of non pharmacological interventions able to slow down patients' cognitive decline in the absence of disease-modifying treatments. We aimed at identifying the neurobiological substrates of CR (i.e., neural reserve) over the transition between normal aging and AD, by assessing the underlying brain networks and their topological properties. A cohort of 154 participants (n = 68 with AD, n = 61 with amnestic mild cognitive impairment (aMCI), and 25 healthy subjects) underwent resting-state functional MRI and neuropsychological testing. Within each group, participants were classified as having high or low CR, and functional connectivity measures were compared, within group, between high and low CR individuals. Network-based statistics and topological network properties derived from graph theory were explored. Connectivity differences between high and low CR were evident only for aMCI patients, with participants with high CR showing a significant increase of connectivity in a network involving mainly fronto parietal nodes. Conversely, they showed significantly decreased connectivity in a network involving fronto-temporo-cerebellar nodes. Consistently, changes to topological measures were observed in either direction, and were associated with measures of global cognitive function. These findings support the hypothesis that CR impacts on neurodegenerative process in the early phase of AD only. In addition, they fit with the existence of a "neural reserve", characterized by specific neural networks and their efficiency. It remains to be demonstrated whether interventions later in life can modulate this "neural reserve". PMID- 27662320 TI - Quantitative Magnetic Resonance Abnormalities in Creutzfeldt-Jakob Disease and Fatal Insomnia. AB - BACKGROUND: Quantitative neuroimaging might unveil abnormalities in prion diseases that are not perceivable at visual inspection. On the other hand, scarce studies have quantified volumetric changes in prion diseases. OBJECTIVES: We aim to characterize volumetric and diffusion tensor imaging (DTI) changes in patients with prion diseases who presented with either Creutzfeldt-Jakob disease (CJD) or fatal insomnia (FI) phenotype. METHODS: Twenty patients with prion diseases- 15 with CJD and 5 with fatal insomnia (FI)- and 40 healthy controls were examined with a 3-Tesla magnetic resonance imaging scanner. Images were segmented and normalized with SPM12. DTI maps were obtained with FMRIB Software Library. Whole brain voxel-wise and region-of-interest analyses of volumetric and DTI changes were performed with SPM12. White matter (WM) changes were also analyzed with tract-based spatial statistics. Semiquantitive assessment of neuropathological parameters was compared with DTI metrics in thalamus from 11 patients. RESULTS: Patients with CJD and FI presented significant atrophy in thalamus and cerebellum. In CJD, mean diffusivity (MD) was decreased in striatum and increased in subcortical WM, while both increased and decreased values were observed across different thalamic nuclei. In FI, MD was increased in thalamus and cerebellum. Spongiform change and PrPSc deposition were more intense in thalamus in CJD than in FI, although no significant correlations arose with MD values in the nuclei studied. CONCLUSION: Volumetric and DTI abnormalities suggest a central common role of the thalamus in prion diseases. We report, for the first time, quantitative MRI changes in FI, and provide further evidence of WM involvement in prion diseases. PMID- 27662321 TI - Alzheimer's Disease Severity is Not Significantly Associated with Short Sleep: Survey by Actigraphy on 208 Mild and Moderate Alzheimer's Disease Patients. AB - BACKGROUND: In epidemiological surveys, cognitive decline has been found to be associated with both short and long sleep duration. OBJECTIVE: Our goal was to objectively determine how total sleep time (TST) at night was associated or not with apathy or severity scores in patients with Alzheimer 's disease (AD). METHODS: During an observational first step of a clinical trial, sleep was assessed in institutionalized patients with mild or moderate AD using actigraphy (MW8, Camtech, Cambridge, UK) for 14 consecutive 24-hour periods. Sleep parameters analyzed were: TST, time in bed (TIB), wake after sleep onset (WASO), sleep efficiency (SE) defined by the ratio TST/TIB, in percentage), the number and length of awakenings, the night fragmentation index, the interdaily stability, and intradaily variability indexes. Statistical association analyses were tested between these values and AD apathy and severity scores. RESULTS: 208 individuals coming from 82 centers worldwide (France, Germany, Spain, Italy, Portugal, Poland, United States, Canada, and Australia) and>=50 years old participated. Their average TST was 7 hours and 35 minutes and the average WASO 58 minutes. TST and SE were significantly higher in patients with apathy and the number of awakenings was significantly lower. TST was also positively associated with functional disability (ADCS-ADL scores), but it was not found significantly greater in patients with a moderate AD severity compared to the mild. CONCLUSION: Despite several and long awakenings, TST was not shorter in patients with AD. TST was even significantly increased with disability and apathy. PMID- 27662324 TI - Coexistence of lymphoproliferative and myeloproliferative neoplasms with simultaneous CALR and JAK2 V617F mutations. AB - BACKGROUND: Hematopoietic malignancies are a group of blood cell disorders characterized by abnormal hematopoietic proliferation. OBJECTIVE: The identification of specific clinicopathologic characteristics and tumor-related gene status provides critical information on potential therapeutic targets. METHODS: The specimens were tested with immunohistochemistry, flow cytometry, RT PCR and fragment analysis. RESULTS: In this study, a patient with a long history of tobacco use was reported with a diagnosis of simultaneous low-grade B-cell lymphoproliferative disorder (LPD) and myeloproliferative neoplasm (MPN). Mutational analysis revealed that JAK2 V617F mutation and CALR mutation with 52bp deletion were present in this patient. CONCLUSION: These results suggest that lymphoproliferative and myeloproliferative neoplasms may coexist, although the pathogenetic mechanism of coexisting hematologic requires further investigation. Additionally, the data indicate that JAK2 V617F and CALR mutations are not mutually exclusive and the actual frequency of simultaneous JAK2 V617F and CALR mutations is unknown. Whether the coexistence of these mutations imposes any biological or clinical significance awaits further investigation. PMID- 27662318 TI - Mitochondrial Dysfunction and Synaptic Transmission Failure in Alzheimer's Disease. AB - Alzheimer's disease (AD) is a chronic neurodegenerative disorder, in which multiple risk factors converge. Despite the complexity of the etiology of the disease, synaptic failure is the pathological basis of cognitive impairment, the cardinal sign of AD. Decreased synaptic density, compromised synaptic transmission, and defected synaptic plasticity are hallmark synaptic pathologies accompanying AD. However, the mechanisms by which synapses are injured in AD related conditions have not been fully elucidated. Mitochondria are a critical organelle in neurons. The pivotal role of mitochondria in supporting synaptic function and the concomitant occurrence of mitochondrial dysfunction with synaptic stress in postmortem AD brains as well as AD animal models seem to lend the credibility to the hypothesis that mitochondrial defects underlie synaptic failure in AD. This concept is further strengthened by the protective effect of mitochondrial medicine on synaptic function against the toxicity of amyloid-beta, a key player in the pathogenesis of AD. In this review, we focus on the association between mitochondrial dysfunction and synaptic transmission deficits in AD. Impaired mitochondrial energy production, deregulated mitochondrial calcium handling, excess mitochondrial reactive oxygen species generation and release play a crucial role in mediating synaptic transmission deregulation in AD. The understanding of the role of mitochondrial dysfunction in synaptic stress may lead to novel therapeutic strategies for the treatment of AD through the protection of synaptic transmission by targeting to mitochondrial deficits. PMID- 27662323 TI - Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients. AB - INTRODUCTION: The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. MATERIALS AND METHODS: The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. RESULTS: The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P < 0.05), but there was no significant difference in the content of the above factors in the serum sample between two groups. There was no significant difference in the ErbB2 content in the saliva, serum or local tumor-exfoliated cells between two groups. CONCLUSION: Survivin and CEA levels are significantly increased in the saliva and local tumor-exfoliated cells in OSCC patients, and they can be used as reliable markers for the early detection of oral malignant cancer. PMID- 27662322 TI - Role of Glutamate and NMDA Receptors in Alzheimer's Disease. AB - Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive NMDAR activity causes excitotoxicity and promotes cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer's disease (AD). Studies indicate that the distinct outcomes of NMDAR-mediated responses are induced by regionalized receptor activities, followed by different downstream signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs promotes cell death and thus contributes to the etiology of AD, which can be blocked by an AD drug, memantine, an NMDAR antagonist that selectively blocks the function of extrasynaptic NMDARs. PMID- 27662326 TI - Acute Hospital Admissions of Individuals with a Known Parkinson's Disease Diagnosis in Ireland 2009-2012: A Short Report. AB - BACKGROUND: The rate of people with Parkinson's disease (PD) is predicted to double by 2030 resulting in an even greater burden to an already struggling Irish health care system. There is a paucity of information regarding hospital utilisation among the PD population in an Irish context. OBJECTIVE: To examine trends of acute hospital in-patient admissions of patients admitted with a secondary diagnosis of PD between 2009 and 2012 in Ireland. METHOD: Data concerning patients, aged over and under 65 years with a previously existing diagnosis of Parkinson's Disease were requested from the HIPE database for the years 2009-2012. Primary categories of interest were the top 10 principal diagnoses on admission, the top 10 principal procedures conducted, admission source and route, and final discharge destination. RESULTS: 12,437 discharges were recorded for people with PD over the age of 65 years and 1,223 in those under 65 years in Republic of Ireland between 2009 and 2012. A steady rise in acute hospital admissions was noted in the over 65 group. The number of patients requiring long stay accommodation more than doubled across both age categories from admission to discharge status. The most common reasons for admission in all age ranges were acute lower respiratory infection; disorders of urinary system; pneumonia (organism unspecified); and pneumonitis due to solids and liquids (aspiration pneumonia). CONCLUSIONS: This report highlights a worrying trend towards increased rates of hospital admissions for pneumonia and infections for people living with PD in Republic of Ireland. PMID- 27662325 TI - Articulation Features of Parkinson's Disease Patients with Subthalamic Nucleus Deep Brain Stimulation. AB - BACKGROUND: Voice and speech disorders are one of the most important issues after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. However, articulation features in this patient population remain unclear. OBJECTIVE: We studied the articulation features of PD patients with STN DBS. METHODS: Participants were 56 PD patients treated with STN-DBS (STN-DBS group) and 41 patients treated only with medical therapy (medical-therapy-alone group). Articulation function was evaluated with acoustic and auditory-perceptual analyses. The vowel space area (VSA) was calculated using the formant frequency data of three vowels (/a/, /i/, and /u/) from sustained phonation task. The VSA reportedly reflects the distance of mouth/jaw and tongue movements during speech and phonation. Correlations between acoustic and auditory-perceptual measurements were also assessed. RESULTS: The VSA did not significantly differ between the medical-therapy-alone group and the STN-DBS group in the off-stimulation condition. In the STN-DBS group, the VSA was larger in the on-stimulation condition than in the off-stimulation condition. However, individual analysis showed the VSA changes after stopping stimulation were heterogeneous. In total, 89.8% of the STN-DBS group showed a large VSA size in the on- than in the off stimulation condition. In contrast, the VSA of the remaining patients in that group was smaller in the on- than the off-stimulation condition. CONCLUSIONS: STN DBS may resolve hypokinesia of the articulation structures, including the mouth/jaw and tongue, and improve maximal vowel articulation. However, in the on stimulation condition, the VSA was not significantly correlated with speech intelligibility. This may be because STN-DBS potentially affects other speech processes such as voice and/or respiratory process. PMID- 27662327 TI - Prevalence and Prescribed Treatments of Orthostatic Hypotension in Institutionalized Patients with Parkinson's Disease. AB - BACKGROUND: Orthostatic hypotension (OH) in Parkinson's disease (PD) is a common non-motor sign that can be hard to recognize and treat. OH prevalence and treatment in institutionalized PD-patients remains unknown. OBJECTIVE: The aim of this study was to explore the prevalence and prescribed treatments of OH in institutionalized patients with PD. METHOD: A cross-sectional study of nursing homes in the south-east of the Netherlands identified 64 residents with PD (inclusion criteria: MMSE >18). Assessments included blood pressure measurement, both supine and in the upright position (after 1 minute and after 3 minutes of standing), and 2 questions on cardiovascular items including falls of the validated Non-Motor Symptom Scale (NMSS). OH was defined according to the consensus guidelines. OH was considered as 'probably symptomatic' if patients had a concomitant frequency score >1 on the selected NMSS items, and 'probably asymptomatic' for a frequency score of 0. If OH was not present, but patients had a frequency score >1, OH was considered as 'possibly symptomatic'. RESULTS: The prevalence of OH was 51.6%, almost equally divided into probably symptomatic and probably asymptomatic cases. Another 20.6% had possibly symptomatic OH. Importantly, only two patients with symptomatic OH had an OH diagnosis noted in their medical records. Five received domperidone, one received fludrocortison and none received midodrine. CONCLUSION: One half of institutionalized PD patients had OH, of whom half were probably symptomatic. OH was rarely noted in the medical records, suggesting underdiagnosis. Finally, OH was rarely treated, suggesting undertreatment. PMID- 27662328 TI - Personalized Medicine Approaches in Parkinson's Disease: The Genetic Perspective. AB - Recent discoveries with respect to the genetic and molecular basis of Parkinson's disease have led to an increasing recognition of the etiologic heterogeneity of the disorder. As in other complex diseases, it is hoped that this knowledge will allow the identification of novel therapeutic targets that will eventually lead to a more efficient treatment, based on the patient's individual genetic predispositions. PMID- 27662329 TI - Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study. AB - BACKGROUND: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). OBJECTIVE: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. METHODS: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. RESULTS: NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. CONCLUSION: This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy. PMID- 27662330 TI - Subjective Perceived Motor Improvement after Acute Levodopa Challenge in Parkinson's Disease. AB - BACKGROUND: Previous studies found a poor association between parkinsonian patient's reported subjective improvement after commencing dopaminergic treatment and improvements in objective measures of motor impairment by clinician. OBJECTIVE: To compare PD patient's subjective perceived motor improvement after acute levodopa challenge test with objective motor improvement assessed by the clinician using the UPDRS part III. To analyze clinical characteristics, i.e. age, disease duration, cognitive performance or severity of axial features, that may have influenced patient's perception. METHODS: Fifty-seven consecutive PD patients (23 women, 34 men; mean age, 63.4+/-7.7 years) (Hoehn and Yahr off score, 2.5+/-0.7; mean disease duration, 11.4+/-4.1 years) completed the acute levodopa challenge. The percentage of improvement in motor disability, i.e. objective motor improvement, was determined with respect to the off-drug condition. RESULTS: Bland & Altman visual analysis reveals a high degree of correlation between objective and subjective perceived motor improvement. Both the axial sub-scores in the off- and on-state (respectively, P = 0.006 and P = 0.024) and the presence of peak-dose dyskinesia (P = 0.043) significantly influence the difference between objective and subjective perceived motor improvement. CONCLUSIONS: This is the first study reporting on how PD patients assessed their motor improvement after acute levodopa challenge. These findings suggest a strong correlation between objective motor improvement assessed by the clinician using the UPDRS part III and subjective perceived motor improvement reported by the patient. PMID- 27662331 TI - The Practicalities of Assessing Freezing of Gait. AB - BACKGROUND: Freezing of gait (FOG) is a mysterious, complex and debilitating phenomenon in Parkinson's disease. Adequate assessment is a pre-requisite for managing FOG, as well as for assigning participants in FOG research. The episodic nature of FOG, as well as its multiple clinical expressions make its assessment challenging. OBJECTIVE: To highlight the available assessment tools and to provide practical, experience-based recommendations for reliable assessment of FOG. METHODS: We reviewed FOG assessment from history taking, questionnaires, lab and home-based measurements and examined how these methods account for presence and severity of FOG, their limits and advantages. The practicalities for their use in clinical and research practice are highlighted. RESULTS: According to the available assessment tools severity of FOG is marked by one or a combination of multiple clinical expressions including frequency, duration, triggering circumstances, response to levodopa, association with falls and fear of falling, or need for assistance to avoid falls. CONCLUSIONS: To date, a unique methodological tool that encompasses the entire complexity of FOG is lacking. Combining methods should give a better picture of FOG severity, in accordance with the precise clinical or research context. Further development of any future assessment tool requires understanding and thorough analysis of the specific clinical expressions of FOG. PMID- 27662333 TI - Tremor Frequency Assessment by iPhone(r) Applications: Correlation with EMG Analysis. AB - Tremor frequency analysis is usually performed by EMG studies but accelerometers are progressively being more used. The iPhone(r) contains an accelerometer and many applications claim to be capable of measuring tremor frequency. We tested three applications in twenty-two patients with a diagnosis of PD, ET and Holmes' tremor. EMG needle assessment as well as accelerometry was performed at the same time. There was very strong correlation (Pearson >0.8, p < 0.001) between the three applications, the EMG needle and the accelerometry. Our data suggests the apps LiftPulse(r), iSeismometer(r) and Studymytremor(r) are a reliable alternative to the EMG for tremor frequency assessment. PMID- 27662332 TI - Muscarinic M1 Receptor Coupling to G-protein is Intact in Parkinson's Disease Dementia. AB - BACKGROUND: Postsynaptic cholinergic deficits, including reduced cortical muscarinic M1 receptor coupling to G-proteins, are neurochemical findings postulated to underlie the limited efficacy of presynaptically-targeted cholinergic replacement therapies in Alzheimer's disease (AD). While the loss of M1-G-protein coupling has been associated with beta-amyloid (Abeta) burden in AD, the status of M1 coupling to G-proteins in Parkinson's disease-related or mixed dementias is unclear. OBJECTIVE: To test the hypothesis that M1 receptor uncoupling is correlated with Abeta burden, we aimed to study muscarinic M1 neurochemical parameters in neurodegenerative dementias characterized by low and high Abeta loads. METHODS: M1 receptors, M1 coupling to G-proteins as well as Abeta were measured in postmortem frontal cortex of a cohort of longitudinally assessed patients with Parkinson's Disease Dementia (PDD, low Abeta load) and AD with significant subcortical cerebrovascular disease (AD + CVD, high Abeta load). RESULTS: We found unchanged levels of M1 receptors in both dementia groups, while M1 coupling was reduced only in AD + CVD (p < 0.01). Furthermore, Abeta concentration was significantly increased only in AD + CVD, and correlated negatively with M1-G-protein coupling in the dementia groups. CONCLUSIONS: Our study suggests that loss of M1 coupling to G-proteins may be a neurochemical feature of neurodegenerative dementias with high cortical Abeta burden, and that cholinergic replacement therapies may be more efficacious for PDD due to low Abeta burden. PMID- 27662338 TI - Patchy and Janus Nanoparticles by Self-Organization of Mixtures of Fluorinated and Hydrogenated Alkanethiolates on the Surface of a Gold Core. AB - The spontaneous self-organization of dissimilar ligands on the surface of metal nanoparticles is a very appealing approach to obtain anisotropic "spherical" systems. In addition to differences in ligand length and end groups, a further thermodynamic driving force to control the self-assembled monolayer organization may become available if the ligands are inherently immiscible, as is the case of hydrogenated (H-) and fluorinated (F-) species. Here, we validate the viability of this approach by combining 19F NMR experiments and multiscale molecular simulations on large sets of mixed-monolayer-protected gold nanoparticles (NPs). The phase segregation of blends of F- and H-thiolates grafted on the surface of gold NPs allows a straightforward approach to patterned mixed monolayers, with the shapes of the monolayer domains being encoded in the structure of the F/H thiolate ligands. The results obtained from this comprehensive study offer molecular design rules to achieve a precise control of inorganic nanoparticles protected by specifically patterned monolayers. PMID- 27662336 TI - Characteristics of EEG Interpreters Associated With Higher Interrater Agreement. AB - PURPOSE: The goal of the project is to determine characteristics of academic neurophysiologist EEG interpreters (EEGers), which predict good interrater agreement (IRA) and to determine the number of EEGers needed to develop an ideal standardized testing and training data set for epileptiform transient (ET) detection algorithms. METHODS: A three-phase scoring method was used. In phase 1, 19 EEGers marked the location of ETs in two hundred 30-second segments of EEG from 200 different patients. In phase 2, EEG events marked by at least 2 EEGers were annotated by 18 EEGers on a 5-point scale to indicate whether they were ETs. In phase 3, a third opinion was obtained from EEGers on any inconsistencies between phase 1 and phase 2 scoring. RESULTS: The IRA for the 18 EEGers was only fair. A select group of the EEGers had good IRA and the other EEGers had low IRA. Board certification by the American Board of Clinical Neurophysiology was associated with better IRA performance but other board certifications, years of fellowship training, and years of practice were not. As the number of EEGers used for scoring is increased, the amount of change in the consensus opinion decreases steadily and is quite low as the group size approaches 10. CONCLUSIONS: The IRA among EEGers varies considerably. The EEGers must be tested before use as scorers for ET annotation research projects. The American Board of Clinical Neurophysiology certification is associated with improved performance. The optimal size for a group of experts scoring ETs in EEG is probably in the 6 to 10 range. PMID- 27662335 TI - Similar Progression of Morphological and Metabolic Phenotype in R6/2 Mice with Different CAG Repeats Revealed by In Vivo Magnetic Resonance Imaging and Spectroscopy. AB - BACKGROUND: Huntington's disease (HD) is caused by an unstable polyglutamine (CAG) repeat in the HD gene, whereby a CAG repeat length greater than ~36 leads to the disease. In HD patients, longer repeats correlate with more severe disease and earlier death. This is also seen in R6/2 mice carrying repeat lengths up to ~200. Paradoxically, R6/2 mice with repeat lengths >300 have a less aggressive phenotype and longer lifespan than those with shorter repeats. The mechanism underlying this phenomenon is unknown. OBJECTIVE: To investigate the consequences of longer repeat lengths on structural changes in the brains of R6/2 mice, especially with regard to progressive atrophy. METHODS: We used longitudinal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) to compare pathological changes in two strains of R6/2 mice, one with a rapidly progressing disease (250 CAG repeats), and the other with a less aggressive phenotype (350 CAG repeats). RESULTS: We found significant progressive brain atrophy in both 250 and 350 CAG repeat mice, as well as changes in metabolites (glutamine/glutamate, choline and aspartate). Although similar in magnitude, atrophy in the brains of 350 CAG R6/2 mice progressed more slowly than that seen in 250 CAG mice, in line with the milder phenotype and longer lifespan. Interestingly, significant atrophy was detectable in 350 CAG mice as early as 8-12 weeks of age, although behavioural abnormalities in these mice are not apparent before 25-30 weeks. This finding fits well with human data from the PREDICT-HD and TRACK-HD project, where reductions in brain volume were found 10 years in advance of the onset of symptoms. CONCLUSIONS: The similar brain atrophy with a mismatch between onset of brain atrophy and behavioural phenotype in HD mice with 350 repeats will make this mouse particularly useful for modelling early stages of HD pathology. PMID- 27662334 TI - Oxidative Stress and Huntington's Disease: The Good, The Bad, and The Ugly. AB - Redox homeostasis is crucial for proper cellular functions, including receptor tyrosine kinase signaling, protein folding, and xenobiotic detoxification. Under basal conditions, there is a balance between oxidants and antioxidants. This balance facilitates the ability of oxidants, such as reactive oxygen species, to play critical regulatory functions through a direct modification of a small number of amino acids (e.g. cysteine) on signaling proteins. These signaling functions leverage tight spatial, amplitude, and temporal control of oxidant concentrations. However, when oxidants overwhelm the antioxidant capacity, they lead to a harmful condition of oxidative stress. Oxidative stress has long been held to be one of the key players in disease progression for Huntington's disease (HD). In this review, we will critically review this evidence, drawing some intermediate conclusions, and ultimately provide a framework for thinking about the role of oxidative stress in the pathophysiology of HD. PMID- 27662339 TI - Radiotherapy to Control Limited Melanoma Progression Following Ipilimumab. AB - Durable local control of irradiated cancer and distant abscopal effects are presumably immune mediated. To evaluate the role of radiotherapy (RT) for limited progression after anti-CTLA4 checkpoint inhibition, medical records of all patients with surgically incurable stage III or IV melanoma from a single institution who received ipilimumab as first-line immunotherapy and subsequent RT were reviewed. Sixteen patients who received RT to all sites of limited melanoma progression were analyzed. Eight patients with an incomplete initial response to ipilimumab received RT to new or progressive disease, whereas the remaining 8 patients with a complete initial response to ipilimumab received RT to sites of subsequent recurrence. The median interval from ipilimumab initiation to start of RT was 30 weeks (range, 15-130 wk), a timeframe where delayed response to ipilimumab is rare. The RT dose was predominantly 30 Gy in 5 fractions (41%) or 36 Gy in 6 fractions (26%). Brain radiation was limited to stereotactic radiosurgery in a single patient. The median local control with RT was 31.4 months. The median disease control was 18.7 months, defined as the interval from completion of RT to the start of additional systemic therapy known to impact survival (anti-programmed death-1 or targeted BRAF therapy), hospice enrollment, or death. The overall survival at 1 and 2 years was 87% and 61%, respectively. Seven patients (44%) had no evidence of melanoma at median follow-up of 29.5 months since completion of RT with no additional therapy. This series supports use of RT to limited sites of progression following ipilimumab as an alternative to other systemic treatments such as anti-programmed death-1 antibodies. PMID- 27662340 TI - Pembrolizumab-triggered Uveitis: An Additional Surrogate Marker for Responders in Melanoma Immunotherapy? AB - Immunotherapy leads to significantly prolonged survival of patients with metastatic melanoma. Autoimmune side effects including colitis, dermatitis, and endocrine abnormalities are common in patients treated with ipilimumab [anti CTLA4 (cytotoxic T-lymphocyte-associated protein 4)]. Antibodies such as pembrolizumab that interfere with the PD-1 (programmed cell death 1)/PD-L1 pathway show greater efficacy and less toxicity than ipilimumab. Here we report 2 cases of pembrolizumab-induced uveitis associated with complete or partial tumor response. We suggest that uveitis may serve as a surrogate marker for a tumor response to therapy with pembrolizumab. PMID- 27662341 TI - Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo controlled, crossover study. AB - BACKGROUND: Increasing evidence suggests photoprotection by oral supplementation with beta-carotene and lycopene. OBJECTIVES: To examine the capacity of lycopene rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. METHODS: In a placebo controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2 week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. RESULTS: TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0.05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. CONCLUSIONS: Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage. PMID- 27662344 TI - AsMA, A Global Organisation. PMID- 27662342 TI - Template-Based Modeling of Protein-RNA Interactions. AB - Protein-RNA complexes formed by specific recognition between RNA and RNA-binding proteins play an important role in biological processes. More than a thousand of such proteins in human are curated and many novel RNA-binding proteins are to be discovered. Due to limitations of experimental approaches, computational techniques are needed for characterization of protein-RNA interactions. Although much progress has been made, adequate methodologies reliably providing atomic resolution structural details are still lacking. Although protein-RNA free docking approaches proved to be useful, in general, the template-based approaches provide higher quality of predictions. Templates are key to building a high quality model. Sequence/structure relationships were studied based on a representative set of binary protein-RNA complexes from PDB. Several approaches were tested for pairwise target/template alignment. The analysis revealed a transition point between random and correct binding modes. The results showed that structural alignment is better than sequence alignment in identifying good templates, suitable for generating protein-RNA complexes close to the native structure, and outperforms free docking, successfully predicting complexes where the free docking fails, including cases of significant conformational change upon binding. A template-based protein-RNA interaction modeling protocol PRIME was developed and benchmarked on a representative set of complexes. PMID- 27662345 TI - Flipping a Switch "Down" When Not Aligned with the Gravitational Vertical. AB - INTRODUCTION: To flip a switch "down," our motor system can normally rely on concordant visual, gravitational, and egocentric cues about the vertical. However, divers must sometimes perform this task while visual cues are limited and gravitational cues are misaligned with egocentric cues. Astronauts must also flip switches "down" in absence of gravitational cues. Our study evaluates this ability using a laboratory simulation. METHODS: The subjects were 24 healthy volunteers who were blindfolded, tilted into different angles of roll, and asked to silence an alarm by flipping a switch "down." The switch was constructed such that it could be flipped in any direction in the subjects' frontal plane. RESULTS: Two subjects deflected the switch in accordance with the direction of gravity, irrespective of their body orientation. Twenty subjects deflected it in accordance with their body orientation, irrespective of the direction of gravity. The remaining two persons could not be classified unequivocally. Notably, some egocentric responders deflected the rod consistently toward their feet, but others deflected it consistently toward other parts of their body. DISCUSSION: Since our findings disagree with perceptual studies where gravitational rather than egocentric cues predominated in the absence of vision, we posit that perception and action may access distinct internal representations of the vertical. On the practical side, our findings indicate that designers of spaceflight and underwater equipment should not rely on divers' intuitive knowledge on how to flip a switch "down." Bock O, Bury N. Flipping a switch "down" when not aligned with the gravitational vertical. Aerosp Med Hum Perform. 2016; 87(10):838-843. PMID- 27662346 TI - Distortion Product Otoacoustic Emissions and Intracranial Pressure During CSF Infusion Testing. AB - BACKGROUND: A noninvasive method to monitor changes in intracranial pressure (ICP) is required for astronauts on long-duration spaceflight who are at risk of developing the Visual Impairment/Intracranial Pressure syndrome that has some, but not all of the features of idiopathic intracranial hypertension. We assessed the validity of distortion product otoacoustic emissions (DPOAEs) to detect changes in ICP. METHODS: Subjects were eight patients undergoing medically necessary diagnostic cerebrospinal fluid (CSF) infusion testing for hydrocephalus. DPOAE measurements were obtained with an FDA-approved system at baseline and six controlled ICP levels in ~3 mmHg increments in random order, with a range from 10.8 +/- 2.9 mmHg (SD) at baseline to 32.3 +/- 4.1 mmHg (SD) at level 6. RESULTS: For f2 frequencies between 800 and 1700 Hz, when ICP was >= 12 mmHg above baseline ICP, DPOAE angles increased significantly and DPOAE magnitudes decreased significantly, but less robustly. DISCUSSION: Significant changes in DPOAE angle and magnitude are seen when ICP is >= 12 mmHg above a subject's supine baseline ICP during CSF infusion testing. These results suggest that the changes in DPOAE angle and magnitude seen with change in ICP are physiologically based, and suggest that it should be possible to detect pathological ICP elevation using DPOAE measurements. To use DPOAE for noninvasive estimation of ICP during spaceflight will require baseline measurements in the head-up, supine, and head-down positions to obtain baseline DPOAE values at different ICP ranges. Williams MA, Malm J, Eklund A, Horton NJ, Voss SE. Distortion product otoacoustic emissions and intracranial pressure during CSF infusion testing. Aerosp Med Hum Perform. 2016; 87(10):844-851. PMID- 27662347 TI - Pitch-Plane Angular Displacement Perception During Helicopter Flight and Gondola Centrifugation. AB - BACKGROUND: During hovering with a helicopter, an involuntary change in attitude (during brownout) results in reduced lifting force and a horizontal acceleration component. This movement pattern is difficult to perceive via the otolith organs. If the angular displacement occurs rapidly, it will, however, activate the semicircular canals. The major aim of this study was to establish to what extent pitch-plane angular displacements can be perceived based on canal information when there is no tilt stimulus to the otoliths. METHODS: In a helicopter, 9 nonpilots (N) and 8 helicopter pilots (P) underwent 5-6 pitch-forward displacements (magnitude 14-33 degrees , angular velocity 2-7 degrees . s-1). In a swing-out gondola centrifuge, 9 N and 3 P were exposed to a similar canal otolith conflict (acceleration, seated centripetally) with four displacements of 25 degrees and two of 60 degrees . The visually perceived eye level (VPEL) was continuously recorded using an adjustable luminous dot in darkness. For each helicopter dive and centrifuge run the gain was calculated as the ratio (VPEL deflection)/(displacement of helicopter or gondola). RESULTS: In the helicopter there was no difference between N (0.28 +/- 0.13) and P (0.36 +/- 0.22). In the centrifuge the gains were 0.34 +/- 0.18 degrees (25 degrees displacements) and 0.30 +/- 0.16 degrees (60 degrees displacements). Values obtained in the helicopter did not differ significantly from those in the centrifuge. There was a correlation between data obtained during the 25 degrees and 60 degrees displacements in the centrifuge. CONCLUSION: There was a pronounced underestimation of pitch angular displacements in a helicopter. The interindividual variability was considerable. Gains for perceived displacement were similar in helicopter and centrifuge. Tribukait A, Bergsten E, Eiken O. Pitch-plane angular displacement perception during helicopter flight and gondola centrifugation. Aerosp Med Hum Perform. 2016; 87(10):852-861. PMID- 27662349 TI - Subjective Measurements of In-Flight Sleep, Circadian Variation, and Their Relationship with Fatigue. AB - BACKGROUND: This study examined whether subjective measurements of in-flight sleep could be a reliable alternative to actigraphic measurements for monitoring pilot fatigue in a large-scale survey. METHODS: Pilots (3-pilot crews) completed a 1-page survey on outbound and inbound long-haul flights crossing 1-7 time zones (N = 586 surveys) between 53 city pairs with 1-d layovers. Across each flight, pilots documented flight start and end times, break times, and in-flight sleep duration and quality if they attempted sleep. They also rated their fatigue (Samn Perelli Crew Status Check) and sleepiness (Karolinska Sleepiness Scale) at top of descent (TOD). Mixed model ANCOVA was used to identify independent factors associated with sleep duration, quality, and TOD measures. Domicile time was used as a surrogate measure of circadian phase. RESULTS: Sleep duration increased by 10.2 min for every 1-h increase in flight duration. Sleep duration and quality varied by break start time, with significantly more sleep obtained during breaks starting between (domicile) 22:00-01:59 and 02:00-05:59 compared to earlier breaks. Pilots were more fatigued and sleepy at TOD on flights arriving between 02:00-05:59 and 06:00-09:59 domicile time compared to other flights. With every 1 h increase in sleep duration, sleepiness ratings at TOD decreased by 0.6 points and fatigue ratings decreased by 0.4 points. DISCUSSION: The present findings are consistent with previous actigraphic studies, suggesting that self-reported sleep duration is a reliable alternative to actigraphic sleep in this type of study, with use of validated measures, sufficiently large sample sizes, and where fatigue risk is expected to be low. van den Berg MJ, Wu LJ, Gander PH. Subjective measurements of in-flight sleep, circadian variation, and their relationship with fatigue. Aerosp Med Hum Perform. 2016; 87(10):869-875. PMID- 27662348 TI - Prognostic Factors for Outcomes of In-Flight Sudden Cardiac Arrest on Commercial Airlines. AB - BACKGROUND: In-flight cardiac arrest (IFCA) is a relatively rare but challenging event. Outcomes and prognostic factors are not entirely understood for victims of IFCAs in commercial aviation. METHODS: This was a retrospective cohort study of airline passengers who experienced IFCA. Demographic and operational variables were studied to identify association in a multivariate logistic regression model with the outcome of survival-to-hospital. In-flight medical emergencies were processed by a ground-based medical center. Subsequent comparisons were made between reported shockable-rhythm (RSR) and reported non-shockable-rhythm (RNSR) groups. Logistic regression was also used to identify predictors for shock advised and flight diversions using a case control study design. Significant predictors for survival-to-hospital were RSR and remaining flight time to destination. RESULTS: The percentage of RSR cases was 24.6%. The survival to hospital admission was 22.7% (22/97) for passengers in RSR compared with 2.4% (7/297) in the RNSR group. The adjusted odds ratio for survival-to-hospital for the RSR group compared to the RNSR group was 13.6 (5.5-33.5). The model showed odds for survival to hospital decreased with longer scheduled remaining flight duration with adjusted OR = 0.701 (0.535-0.920) per hour increase. No correlation between diversions and survival for RSR cases was found. CONCLUSIONS: Survival-to hospital from IFCAs is best when an RSR is present. The percentage of RSR cases was lower than in other out-of-hospital cardiac arrest (OHCA) settings, which suggests delayed discovery. Flight diversions did not significantly affect resuscitation outcome. We emphasize good quality cardio-pulmonary resuscitation (CPR) and early defibrillation as key factors for IFCA survival. Alves PM, DeJohn CA, Ricaurte EM, Mills WD. Prognostic factors for outcomes of in-flight sudden cardiac arrest on commercial airlines. Aerosp Med Hum Perform. 2016; 87(10):862 868. PMID- 27662351 TI - Screening and Mitigation of Layperson Anxiety in Aerospace Environments. AB - INTRODUCTION: Anxiety may present challenges for commercial spaceflight operations, as little is known regarding the psychological effects of spaceflight on laypersons. A recent investigation evaluated measures of anxiety during centrifuge-simulated suborbital commercial spaceflight, highlighting the potential for severe anxiousness to interrupt spaceflight operations. METHODS: To pave the way for future research, an extensive literature review identified existing knowledge that may contribute to formation of interventions for anxiety in commercial spaceflight. Useful literature was identified regarding anxiety from a variety of fields, including centrifugation, fear of flying, motion sickness, and military operations. RESULTS: Fear of flying is the most extensively studied area, with some supportive evidence from centrifugation studies. Virtual reality exposure (VRE) is as effective as actual training flight exposure (or analog exposure) in mitigation of flight-related anxiety. The addition of other modalities, such as cognitive behavioral therapy or biofeedback, to VRE improves desensitization compared to VRE alone. Motion sickness-susceptible individuals demonstrate higher trait anxiety than nonsusceptible individuals; for this reason, motion sickness susceptibility questionnaires may be useful measures to identify at-risk individuals. Some military studies indicate that psychiatric history and personality classification may have predictive value in future research. Medication countermeasures consisting of benzodiazepines may quell in-flight anxiety, but do not likely improve anxiety on repeat exposure. DISCUSSION: The scarce available literature addressing anxiety in unique environments indicates that training/repeated exposure may mitigate anxiety. Anxiety and personality indices may be helpful screening tools, while pharmaceuticals may be useful countermeasures when needed. Mulcahy RA, Blue RS, Vardiman JL, Castleberry TL, Vanderploeg JM. Screening and mitigation of layperson anxiety in aerospace environments. Aerosp Med Hum Perform. 2016; 87(10):882-889. PMID- 27662350 TI - Middle Ear Resonance Frequency in Pilots and Pilot Candidates. AB - BACKGROUND: Barotrauma is a frequent problem in aviation medicine. Eustachian tube dysfunction plays a critical role in the pathogenesis of barotrauma. Function of the Eustachian tube can be indirectly assessed by multifrequency tympanometry, which provides valuable information about the resistance and permeability of the middle ear in a wide frequency range. The aim of this study was to research whether multifrequency tympanometry could be used for assessing middle ear impairments in pilots. METHODS: There were 140 pilots and pilot candidates between the ages of 20-55 with normal otoscopic examination who were evaluated by audiological test batteries. Body mass index values, flight hours, audiometric pure tone thresholds, tympanometry and multifrequency tympanometry test results were noted. RESULTS: There was statistically significant decrease in the multifrequency tympanometry measurements of the left and right ears of the pilots with 200-3000 flight hours compared to pilot candidates, and similarly, the pilots with 3000-10,000 flight hours compared to pilot candidates. DISCUSSION: Multifrequency tympanometry values changed between pilot candidates and pilots. However, the values of multifrequency tympanometry did not change due to flight hours. This test battery should not be used for follow up of pilots in the clinic. Tuncer MM, Babakurban ST, Aydin E. Middle ear resonance frequency in pilots and pilot candidates. Aerosp Med Hum Perform. 2016; 87(10):876-881. PMID- 27662352 TI - Spatial Disorientation Training in the Rotor Wing Flight Simulator. AB - BACKGROUND: This study is intended to identify efficacy, evolving applications, best practices, and challenges of spatial disorientation (SD) training in flight simulators for rotor wing pilots. METHODS: Queries of a UK Ministry of Defense research database and Pub Med were undertaken using the search terms 'spatial disorientation,' 'rotor wing,' and 'flight simulator.' Efficacy, evolving applications, best practices, and challenges of SD simulation for rotor wing pilots were also ascertained through discussion with subject matter experts and industrial partners. Expert opinions were solicited at the aeromedical physiologist, aeromedical psychologist, instructor pilot, aeromedical examiner, and corporate executive levels. RESULTS: Peer review literature search yielded 129 articles, with 5 relevant to the use of flight simulators for the spatial disorientation training of rotor wing pilots. Efficacy of such training was measured subjectively and objectively. A preponderance of anecdotal reports endorse the benefits of rotor wing simulator SD training, with a small trial substantiating performance improvement. Advancing technologies enable novel training applications. The mobile nature of flight students and concurrent anticollision technologies can make long-range assessment of SD training efficacy challenging. Costs of advanced technologies could limit the extent to which the most advanced simulators can be employed across the rotor wing community. DISCUSSION: Evidence suggests the excellent training value of rotor wing simulators for SD training. Objective data from further research, particularly with regards to evolving technologies, may justify further usage of advanced simulator platforms for SD training and research. Powell-Dunford N, Bushby A, Leland RA. Spatial disorientation training in the rotor wing flight simulator. Aerosp Med Hum Perform. 2016; 87(10):890-893. PMID- 27662353 TI - Elevated End-Tidal Pco2 During Long-Duration Spaceflight. AB - BACKGROUND: Elevated ambient Pco2 in the International Space Station (ISS) has been cited as a potential contributor to the vision impairment intracranial pressure syndrome (VIIP), a significant health risk for astronauts during long duration space missions. The elevation in ambient Pco2 is rather modest and normal respiratory compensation could minimize the impact on arterial Pco2. METHODS: In nine male astronauts, breaths measured prior to a rebreathing maneuver were examined to assess inspired and end-tidal Pco2 during upright seated preflight and in-flight conditions. RESULTS: Inspired Pco2 increased from preflight baseline (0.6 +/- 0.1 mmHg) to in flight (3.8 +/- 0.4 mmHg). End-tidal Pco2 also increased from preflight baseline (36.0 +/- 3.2 mmHg) to in flight (42.1 +/- 3.7 mmHg). The difference between end-tidal Pco2 comparing in flight to preflight (6.1 +/- 1.6 mmHg) was greater than the difference between inspired Pco2 comparing preflight to in flight (3.3 +/- 0.5 mmHg). DISCUSSION: The greater increase in end-tidal vs. inspired Pco2 might reflect alveolar hypoventilation due to differences in ventilatory control with spaceflight. These data suggest that further studies should focus on arterial Pco2 and acid-base balance to determine if CO2 dilates cerebral and retinal vessels and might contribute to the incidence of VIIP in astronauts. Hughson RL, Yee NJ, Greaves DK. Elevated end tidal Pco2 during long-duration spaceflight. Aerosp Med Hum Perform. 2016; 87(10):894-897. PMID- 27662354 TI - Lipid Subhyaloid Maculopathy and Exposure to High Altitude. AB - BACKGROUND: High altitude retinopathy (HAR) includes a number of diseases related to high altitude such as acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). High altitude retinopathy is mainly characterized by retinal hemorrhages, usually sparing the macular region, a condition specifically known as high altitude retinal hemorrhages (HARH). The pathogenesis of HARH is unclear. Many studies show that lack of oxygen causes an inadequate autoregulation of retinal circulation, causing vascular incompetence. Other retinal changes described in HAR have been reported, such as optical disk edema, optic disc hyperemia, cotton wool exudates, venous occlusions, and macular edema. CASE REPORT: In this paper we present a case of an aviator who developed a unilateral maculopathy through subhyaloid lipid accumulation on a climb to the top of Mt. Everest. The clinical findings are suggestive of an apparent case of temporary altitude-induced visual disruption maybe by the same presumable pathogenesis of HARH. Right eye visual loss was perceived at 5150 m when he was trying to take a photograph 40 d into the expedition. DISCUSSION: The maculopathy developed by this patient adds to the discussion on the pathogenesis of HARH, especially the aspect of this maculopathy and its complete resolution. It seems that autoregulation failure could lead to exudation and lipid deposits in the foveal area. Although macular damage is not a common signal in HARH, checking visual acuity during high altitude expeditions remains an important procedure to avoid late diagnosis as unilateral blindness may not be detected early. Rosas Petrocinio R, Gomes ED. Lipid subhyaloid maculopathy and exposure to high altitude. Aerosp Med Hum Perform. 2016; 87(10):898-900. PMID- 27662355 TI - Fighter Pilot with Recurrent Central Serous Chorioretinopathy. AB - BACKGROUND: Central serous chorioretinopathy (CSC) is usually a self-limiting condition; however, there is potential for recurrence and permanent visual defects. Aviation demands perfect vision to minimize risk to pilots and aircraft. Consequently, this ailment disqualifies pilots and pilots to be. CASE REPORT: A fully trained fighter pilot with 1260 h in fighter airframes has been contending with central serous chorioretinopathy in the right eye over the course of 3 yr. The condition was diagnosed after the member presented with visual disturbances. His course was followed with multiple treatment modalities: watchful waiting, micropulse laser, and rifampin. His disease responded well with rifampin, but was ultimately stopped secondary to elevated liver enzymes. Micropulse laser failed to resolve subretinal fluid. Ultimately the pilot is left with a chronic area of CSC without visual defects and faces career termination. DISCUSSION: Uncompromised vision is inherently crucial in aerospace careers, especially that of a fighter pilot. With persistent CSC resistant to treatment, there is a risk for progression to permanent visual disturbances and/or defects. Safety concerns of authority figures overseeing pilots and aircraft are warranted. However, the concern could be mitigated in air frames that require two pilots. Another factor partially responsible for ending his career is the fear of G force affecting his prognosis. The author is not aware of any other studies illuminating the effects or consideration of excess G force on subretinal fluid in CSC. This is an area that requires further study. Dietrich KC. Fighter pilot with recurrent central serous chorioretinopathy. Aerosp Med Hum Perform. 2016; 87(10):901-905. PMID- 27662358 TI - Redescription and Geographical Distribution of the Endangered Fish Ossubtus xinguense Jegu 1992 (Characiformes, Serrasalmidae) with Comments on Conservation of the Rheophilic Fauna of the Xingu River. AB - The monotypic species Ossubtus xinguense was originally described based on scarce material putatively divided into juveniles and adults. Ossubtus xinguense has a restricted distribution and was previously known only from a few rapids downstream of the city of Altamira, in the Volta Grande stretch of the Middle Xingu River. Until recently, the species was rare in museums because its habitat (large rapids) is difficult to sample. Large-scale collecting efforts targeting rapids throughout the Xingu River basin have yielded an abundance of new material. Based on an analysis of the type series and freshly preserved specimens, we redescribe O. xinguense and provide detailed osteological descriptions along with comments about its relationships within Serrasalmidae. Furthermore, we expand the geographical distribution of the species and discuss its conservation status. PMID- 27662356 TI - You're the Flight Surgeon. AB - Lenz CR, Shields JL, Morgan AO. You're the flight surgeon: an unusual case of ground-level F-15 decompression illness. Aerosp Med Hum Perform. 2016; 87(10):906 909. PMID- 27662359 TI - Electric Field Keeps Chromophore Planar and Produces High Yield Fluorescence in Green Fluorescent Protein. AB - The green fluorescent protein and its designed variants fluoresce efficiently. Because the isolated chromophore is not fluorescent in a practical sense, it is apparent that the protein environment plays a crucial role in its efficiency. Because of various obstacles in studying excited state dynamics of complex systems, however, the detailed mechanism of this efficiency enhancement is not yet clearly elucidated. Here, by adopting excited state nonadiabatic molecular dynamics simulations together with an interpolated quantum chemical potential model of the chromophore, we find that the strong electric field from the protein matrix contributes dominantly to the motional restriction of the chromophore. The delay in twisting motion subsequently obstructs the nonradiative decay that competes with fluorescence, leading naturally to an enhancement in light-emitting efficiency. Surprisingly, steric constraints make only a minor contribution to these aspects. Through residue specific analyses, we identify a group of key residues that control the excited state behavior. Testing a series of mutant GFPs with different brightnesses also supports the view regarding the importance of protein electrostatics. Our findings may provide a useful guide toward designing new fluorescent chemical systems in the future. PMID- 27662360 TI - Evidence-Based Clinical Practice: Asking Focused Questions (PICO). PMID- 27662362 TI - Pharmacodynamic Impact of Carboxylesterase 1 Gene Variants in Patients with Congestive Heart Failure Treated with Angiotensin-Converting Enzyme Inhibitors. AB - BACKGROUND: Variation in the carboxylesterase 1 gene (CES1) may contribute to the efficacy of ACEIs. Accordingly, we examined the impact of CES1 variants on plasma angiotensin II (ATII)/angiotensin I (ATI) ratio in patients with congestive heart failure (CHF) that underwent ACEI dose titrations. Five of these variants have previously been associated with drug response or increased CES1 expression, i.e., CES1 copy number variation, the variant of the duplicated CES1 gene with high transcriptional activity, rs71647871, rs2244613, and rs3815583. Additionally, nine variants, representatives of CES1Var, and three other CES1 variants were examined. METHODS: Patients with CHF, and clinical indication for ACEIs were categorized according to their CES1 genotype. Differences in mean plasma ATII/ATI ratios between genotype groups after ACEI dose titration, expressed as the least square mean (LSM) with 95% confidence intervals (CIs), were assessed by analysis of variance. RESULTS: A total of 200 patients were recruited and 127 patients (63.5%) completed the study. The mean duration of the CHF drug dose titration was 6.2 (SD 3.6) months. After ACEI dose titration, there was no difference in mean plasma ATII/ATI ratios between subjects with the investigated CES1 variants, and only one previously unexplored variation (rs2302722) qualified for further assessment. In the fully adjusted analysis of effects of rs2302722 on plasma ATII/ATI ratios, the difference in mean ATII/ATI ratio between the GG genotype and the minor allele carriers (GT and TT) was not significant, with a relative difference in LSMs of 0.67 (95% CI 0.43-1.07; P = 0.10). Results of analyses that only included enalapril-treated patients remained non-significant after Bonferroni correction for multiple parallel comparisons (difference in LSM 0.60 [95% CI 0.37-0.98], P = 0.045). CONCLUSION: These findings indicate that the included single variants of CES1 do not significantly influence plasma ATII/ATI ratios in CHF patients treated with ACEIs and are unlikely to be primary determinants of ACEI efficacy. PMID- 27662363 TI - FAF1 mediates regulated necrosis through PARP1 activation upon oxidative stress leading to dopaminergic neurodegeneration. AB - Cumulative damage caused by oxidative stress results in diverse pathological conditions. Therefore, elucidating the molecular mechanisms underlying cell death following oxidative stress is important. Here, we describe a novel role for Fas associated factor 1 (FAF1) as a crucial regulator of necrotic cell death elicited by hydrogen peroxide. Upon oxidative insult, FAF1 translocated from the cytoplasm to the nucleus and promoted the catalytic activation of poly(ADP-ribose) polymerase 1 (PARP1) through physical interaction. Moreover, FAF1 depletion prevented PARP1-linked downstream events involved in the triggering of cell death, including energetic collapse, mitochondrial depolarization and nuclear translocation of apoptosis-inducing factor (AIF), implying that FAF1 has a key role in PARP1-dependent necrosis in response to oxidative stress. We further investigated whether FAF1 might contribute to the pathogenesis of Parkinson's disease through excessive PARP1 activation. Indeed, the overexpression of FAF1 using a recombinant adeno-associated virus system in the mouse ventral midbrain promoted PARP1 activation and dopaminergic neurodegeneration in a 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Collectively, our data demonstrate the presence of an FAF1-PARP1 axis that is involved in oxidative stress-induced necrosis and in the pathology of Parkinson's disease. PMID- 27662364 TI - Leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through AKT-mediated regulation of beta-catenin and FOXO-1. AB - In order to establish infection, intra-macrophage parasite Leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. In the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator AKT for modulating its downstream transcription factors, beta-catenin and FOXO-1. L. donovani-infected RAW264.7 and bone marrow-derived macrophages (BMDM) treated with AKT inhibitor or dominant negative AKT constructs showed decreased anti-inflammatory cytokine production and increased host cell apoptosis resulting in reduced parasite survival. Infection-induced activated AKT triggered phosphorylation-mediated deactivation of its downstream target, GSK-3beta. Inactivated GSK-3beta, in turn, could no longer sequester cytosolic beta-catenin, an anti-apoptotic transcriptional regulator, as evidenced from its nuclear translocation during infection. Constitutively active GSK-3beta-transfected L. donovani-infected cells mimicked the effects of AKT inhibition and siRNA-mediated silencing of beta-catenin led to disruption of mitochondrial potential along with increased caspase-3 activity and IL-12 production leading to decreased parasite survival. In addition to activating anti-apoptotic beta-catenin, phospho-AKT inhibits activation of FOXO 1, a pro-apoptotic transcriptional regulator. Nuclear retention of FOXO-1, inhibited during infection, was reversed when infected cells were transfected with dominant negative AKT constructs. Overexpression of FOXO-1 in infected macrophages not only documented increased apoptosis but promoted enhanced TLR4 expression and NF-kappaB activity along with an increase in IL-1beta and decrease in IL-10 secretion. In vivo administration of AKT inhibitor significantly decreased liver and spleen parasite burden and switched cytokine balance in favor of host. In contrast, GSK-3beta inhibitor did not result in any significant change in infectivity parameters. Collectively our findings revealed that L. donovani triggered AKT activation to regulate GSK-3beta/beta-catenin/FOXO-1 axis, thus ensuring inhibition of both host cell apoptosis and immune response essential for its intra-macrophage survival. PMID- 27662366 TI - Mothers Do Not Show Increased Offspring Avoidance and Elevated Corticosterone Levels during Weaning Conflict in Rats. AB - Parent-offspring conflict is predicted to occur because offspring will demand more parental investment than is optimal for the parent, and is said to be strongest during weaning when parents reduce nursing while offspring continue to demand parental care. While weaning conflict has been shown to be stressful in offspring, little is known about the effects of weaning conflict on mothers. We hypothesized that during weaning mothers have higher levels of stress hormone (corticosterone) compared to early lactation because of increased offspring demand. Further, we predicted that if mothers are given the option to avoid offspring solicitation they would do so and show lower corticosterone levels. We tested our hypotheses in an experimental population of rats in which one group of females was given the opportunity to avoid offspring solicitation. We measured faecal corticosterone metabolite levels using a non-invasive approach, and maternal and offspring behaviours during weaning. In contrast to our predictions, we detected lower levels of corticosterone metabolites during weaning than before, irrespective of cage type. Further, during weaning mothers did not show increased offspring avoidance behaviour although offspring solicitation increased significantly. Our results therefore cast doubt on the generally accepted notion of weaning conflict as a stressful period for mothers characterized by overt offspring solicitation. PMID- 27662367 TI - Construction and Operation Costs of Wastewater Treatment and Implications for the Paper Industry in China. AB - This paper aims to develop a construction and operation cost model of wastewater treatment for the paper industry in China and explores the main factors that determine these costs. Previous models mainly involved factors relating to the treatment scale and efficiency of treatment facilities for deriving the cost function. We considered the factors more comprehensively by adding a regional variable to represent the economic development level, a corporate ownership factor to represent the plant characteristics, a subsector variable to capture pollutant characteristics, and a detailed-classification technology variable. We applied a unique data set from a national pollution source census for the model simulation. The major findings include the following: (1) Wastewater treatment costs in the paper industry are determined by scale, technology, degree of treatment, ownership, and regional factors; (2) Wastewater treatment costs show a large decreasing scale effect; (3) The current level of pollutant discharge fees is far lower than the marginal treatment costs for meeting the wastewater discharge standard. Key implications are as follows: (1) Cost characteristics and impact factors should be fully recognized when planning or making policies relating to wastewater treatment projects or technology development; (2) There is potential to reduce treatment costs by centralizing wastewater treatment via industrial parks; (3) Wastewater discharge fee rates should be increased; (4) Energy efficient technology should become the future focus of wastewater treatment. PMID- 27662365 TI - TRAP1 regulates stemness through Wnt/beta-catenin pathway in human colorectal carcinoma. AB - Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. Indeed, treatment failures are triggered by cancer stem cells (CSCs) that give rise to tumor repopulation upon initial remission. Thus, the role of the heat shock protein TRAP1 in stemness was investigated in CRC cell lines and human specimens, based on its involvement in colorectal carcinogenesis, through regulation of apoptosis, protein homeostasis and bioenergetics. Strikingly, co expression between TRAP1 and stem cell markers was observed in stem cells located at the bottom of intestinal crypts and in CSCs sorted from CRC cell lines. Noteworthy, TRAP1 knockdown reduced the expression of stem cell markers and impaired colony formation, being the CSC phenotype and the anchorage-independent growth conserved in TRAP1-rich cancer cells. Consistently, the gene expression profiling of HCT116 cells showed that TRAP1 silencing results in the loss of the stem-like signature with acquisition of a more-differentiated phenotype and the downregulation of genes encoding for activating ligands and target proteins of Wnt/beta-catenin pathway. Mechanistically, TRAP1 maintenance of stemness is mediated by the regulation of Wnt/beta-catenin signaling, through the modulation of the expression of frizzled receptor ligands and the control of beta-catenin ubiquitination/phosphorylation. Remarkably, TRAP1 is associated with higher expression of beta-catenin and several Wnt/beta-catenin target genes in human CRCs, thus supporting the relevance of TRAP1 regulation of beta-catenin in human pathology. This study is the first demonstration that TRAP1 regulates stemness and Wnt/beta-catenin pathway in CRC and provides novel landmarks in cancer biology and therapeutics. PMID- 27662368 TI - Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali. AB - BACKGROUND: Seasonal malaria chemoprevention (SMC) with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) is being scaled up in Sahelian countries of West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern. METHODS: Two cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3-59 months received 7 rounds of curative doses of SP plus AQ over two malaria seasons. Genotypes of P. falciparum Pfdhfr codons 51, 59 and 108; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1codon 86 were analyzed by PCR on DNA from samples collected before and after SMC, and in non-SMC patient population as controls (November 2014). RESULTS: In the SMC population 191/662 (28.9%) and 85/670 (12.7%) of children were P. falciparum positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the non-SMC patient population 220/310 (71%) were successfully PCR analyzed. In the SMC children, the prevalence of all molecular markers of SP resistance increased significantly after SMC including the Pfdhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p = 0.02). The prevalence of Pfmdr1-86Y significantly decreased from 26.7% to 15.3% (p = 0.04) while no significant change was seen for Pfcrt 76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC population patient (p < 0.01). No Pfdhfr-164 mutation was found neither at baseline nor post SMC. CONCLUSION: SMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant increase of these markers of resistance in the general parasite population after 2 years and 7 rounds of SMC. PMID- 27662369 TI - Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats. AB - Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF alpha and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARalpha were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro inflammatory cytokines in young adult rats with a strong sexual dimorphism. The potential impact of these alterations in early adulthood remains to be elucidated. PMID- 27662370 TI - Brain basis of childhood speech and language disorders: are we closer to clinically meaningful MRI markers? AB - PURPOSE OF REVIEW: Developmental speech and language disorders are common, seen in one in 20 preschool children, in the absence of frank neurological deficits or intellectual impairment. They are a key reason parents seek help from paediatricians. Complex neurogenetic and environmental contributions underpin the disorders, yet few specific causes are known. With the advent of quantitative brain imaging, a growing number of studies have investigated neural contributions. Here, we discuss current MRI approaches and recent findings (January 2014-June 2016) in the field. RECENT FINDINGS: Five relevant studies were identified (n = 3 - speech disorder and n = 2 - language disorder). Significant variability in MRI approaches and heterogeneity of participant phenotypes was seen. Children with speech disorder had structural and functional anomalies in the left supramarginal gyrus and functional anomalies in the posterior cerebellum bilaterally - regions critical for sensory-motor integration or feedback. Children with language disorder showed increased mean and radial diffusivity of the left arcuate fasciculus, although a widespread cortical and subcortical network of regions was implicated. SUMMARY: Limited evidence exists for specific regional brain anomalies in this population. MRI prognostic markers of speech and language ability are not currently available at an individual level. Further work is required to disentangle neurobiological contributions to speech and language disorders for affected children. PMID- 27662371 TI - Analysis of Genome-Wide Monoallelic Expression Patterns in Three Major Cell Types of Mouse Visual Cortex Using Laser Capture Microdissection. AB - Genomic imprinting is an epigenetic mechanism causing monoallelic expression in a parent-of-origin-specific manner. Disruption of imprinted genes causes various neurological and psychiatric disorders. However, the role of imprinted genes in the brain is largely unknown. Different cell types within distinct brain regions can influence the genomic imprinting status, but imprinted genes in single cell types within distinct brain regions have not been characterized on a genome-wide scale. To address this critical question, we used a multi-stage approach, which combined genetically engineered mice with fluorescence-based laser capture microdissection (LCM) to capture excitatory neurons, inhibitory neurons and astrocytes as single cells in layer 2/3 of mouse visual cortex. RNA sequencing determined parental expression patterns on a genome-wide scale in the captured cells within specific brain regions. The expression level of cell-type-specific genes for excitatory neurons (13 genes), inhibitory neurons (16 genes) and astrocytes (20 genes) confirmed the LCM-captured cells maintained their cellular identities. The parent-of-origin-specific expression pattern of imprinted genes, including maternally expressed Meg3 and paternally expressed Peg3, provided evidence that the status of known imprinted genes was also maintained. Although our platform remains to be improved, our findings demonstrate the parental expression pattern can be analysed not only at the level of a single cell type but also at the level of specific cortical layers. Our approach has the potential to reveal novel regulatory modules associated with plasticity through genomic imprinting mechanisms in different cell types, not only in the visual cortex but also in other brain regions. PMID- 27662372 TI - Attaining Proficiency in Robotic-Assisted Minimally Invasive Esophagectomy While Maximizing Safety During Procedure Development. AB - OBJECTIVE: Robotic-assisted minimally invasive esophagectomy (RAMIE) is an emerging complex operation with limited reports detailing morbidity, mortality, and requirements for attaining proficiency. Our objective was to develop a standardized RAMIE technique, evaluate procedure safety, and assess outcomes using a dedicated operative team and 2-surgeon approach. METHODS: We conducted a study of sequential patients undergoing RAMIE from January 25, 2011, to May 5, 2014. Intermedian demographics and perioperative data were compared between sequential halves of the experience using the Wilcoxon rank sum test and the Fischer exact test. Median operative time was tracked over successive 15-patient cohorts. RESULTS: One hundred of 313 esophageal resections performed at our institution underwent RAMIE during the study period. A dedicated team including 2 attending surgeons and uniform anesthesia and OR staff was established. There were no significant differences in age, sex, histology, stage, induction therapy, or risk class between the 2 halves of the study. Estimated blood loss, conversions, operative times, and overall complications significantly decreased. The median resected lymph nodes increased but was not statistically significant. Median operative time decreased to approximately 370 minutes between the 30th and the 45th cases. There were no emergent intraoperative complications, and the anastomotic leak rate was 6% (6/100). The 30-day mortality was 0% (0/100), and the 90-day mortality was 1% (1/100). CONCLUSIONS: Excellent perioperative and short-term patient outcomes with minimal mortality can be achieved using a standardized RAMIE procedure and a dedicated team approach. The structured process described may serve as a model to maximize patients' safety during development and assessment of complex novel procedures. PMID- 27662373 TI - Human Capital, Values, and Attitudes of Persons Seeking Refuge in Austria in 2015. AB - Since its inception in 2010, the Arab Spring has evolved into a situation of violent conflict in many countries, leading to high levels of migration from the affected region. Given the social impact of the large number of individuals applying for asylum across Europe in 2015, it is important to study who these persons are in terms of their skills, motivations, and intentions. DiPAS (Displaced Persons in Austria Survey) aims to uncover the socio-demographic characteristics of the persons seeking refuge who arrived in Austria in 2015, mainly originating from Syria, Iraq and Afghanistan. Particular focus is on human capital, attitudes and values. This survey, the first of its kind in Austria and possibly in Europe, was carried out among adult displaced persons, mostly residing in Vienna, yielding 514 completed interviews. Information gathered on spouses and children allows for the analysis of 972 persons living in Austria, and of further 419 partners and children abroad. Results indicate that the surveyed population comprised mainly young families with children, particularly those coming from Syria and Iraq. Their educational level is high compared with the average level in their country of origin. A vast majority of respondents are Muslims, rating their religiosity at medium levels. Judging from stated attitudes towards gender equity, interviewed men seem to have more liberal attitudes than their compatriots. The majority of respondents do not intend to return to their home countries, mostly because of the perception of permanent threat. DiPAS provides data for political decision-making and the on-going societal dialogue. Its findings can help to inform assessments about the integration potential of the displaced population into the host society. In addition, the applied methodological technique and experiences during the fieldwork provide valuable insights on sampling asylum seekers and refugees in the current European context. PMID- 27662374 TI - Tissue-Specific Stem Cells Obtained by Reprogramming of Non-Obese Diabetic (NOD) Mouse-Derived Pancreatic Cells Confer Insulin Production in Response to Glucose. AB - Type 1 diabetes occurs due to the autoimmune destruction of pancreatic beta-cells in islets. Transplantation of islets is a promising option for the treatment of patients with type 1 diabetes that experience hypoglycemic unawareness despite maximal care, but the present shortage of donor islets hampers such transplantation. Transplantation of insulin-producing cells derived from the patients themselves would be one of the most promising approaches to cure type 1 diabetes. Previously, we demonstrated that insulin-producing cells could be produced by transfecting murine pancreatic cells with Yamanaka's reprogramming factors. Non-obese diabetic (NOD) mice are naturally occurring mutant mice defective in insulin production due to autoimmune ablation of pancreatic beta cells. In this study, we showed that glucose-sensitive insulin-producing cells are successfully generated by transfecting primary pancreatic cells from NOD mice (aged 6 months old) with a plasmid harboring the cDNAs for Oct-3/4, Sox2, Klf4, and c-Myc. Transfection was repeated 4 times in a 2 day-interval. Sixty-five days after final transfection, cobblestone-like colonies appeared. They proliferated in vitro and expressed pluripotency-related genes as well as Pdx1, a transcription factor specific to tissue-specific stem cells for the beta-cell lineage. Transplantation of these cells into nude mice failed to produce teratoma unlike induced pluripotent stem cells (iPSCs). Induction of these cells to the pancreatic beta-cell lineage demonstrated their capability to produce insulin in response to glucose. These findings suggest that functional pancreatic beta-cells can be produced from patients with type 1 diabetes. We call these resultant cells as "induced tissue-specific stem cells from the pancreas" (iTS-P) that could be valuable sources of safe and effective materials for cell-based therapy in type 1 diabetes. PMID- 27662375 TI - Single-molecule fluorescence microscopy of native macromolecular complexes. AB - Macromolecular complexes consisting of proteins, lipids, and/or nucleic acids are ubiquitous in biological processes. Their composition, stoichiometry, order of assembly, and conformations can be heterogeneous or can change dynamically, making single-molecule studies best suited to measure these properties accurately. Recent single-molecule pull-down and other related approaches have combined the principles of conventional co-immunoprecipitation assay with single molecule fluorescence microscopy to probe native macromolecular complexes. In this review, we present the advances in single-molecule pull-down methods and biological systems that have been investigated in such semi vivo manner. PMID- 27662378 TI - The process of internationalization of the nursing and midwifery curriculum: A qualitative study. AB - BACKGROUND: There is an abundance of literature on internationalization of curricula. However, research on how a curriculum is internationalized to accommodate non-mobile students studying in their home countries is limited. OBJECTIVE: To describe the process undertaken by curriculum developers in internationalizing the Brunei nursing and midwifery curriculum through curriculum design. DESIGN: A descriptive qualitative research design. SETTING: A nursing and midwifery higher education institution in Brunei. PARTICIPANTS: Seventeen nurse/midwife academics. METHODS: Semi-structured interviews were conducted with 17 curriculum developers. Data were analyzed using thematic analysis. RESULTS: Four themes emerged: expectations of an internationalized curriculum; formation of a committee; benchmarking and setting standards; and designing the curriculum for internationalization. CONCLUSIONS: This study has implications for the development of an internationally-oriented curriculum that takes into account the cultural context of a specific country. The findings highlight the need to involve students in curriculum design, a practice that is not common in Brunei. PMID- 27662376 TI - Unveiling the functional diversity of the alpha/beta hydrolase superfamily in the plant kingdom. AB - The alpha/beta hydrolase (ABH) superfamily is a widespread and functionally malleable protein fold recognized for its diverse biochemical activities across all three domains of life. ABH enzymes possess unexpected catalytic activity in the green plant lineage through selective alterations in active site architecture and chemistry. Furthermore, the ABH fold serves as the core structure for phytohormone and ligand receptors in the gibberellin, strigolactone, and karrikin signaling pathways in plants. Despite recent discoveries, the ABH family is sparsely characterized in plants, a sessile kingdom known to evolve complex and specialized chemical adaptations as survival responses to widely varying biotic and abiotic ecologies. This review calls attention to the ABH superfamily in the plant kingdom to highlight the functional adaptability of the ABH fold. PMID- 27662377 TI - Microfluidic chip for isolation of viable circulating tumor cells of hepatocellular carcinoma for their culture and drug sensitivity assay. AB - Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device. Efficient capture of HCC CTCs originates from the small dimensions of microfluidic channels and enhanced local topographic interactions between the microfluidic channel and extracellular extensions. With the optimized conditions, a capture yield reached > 85% for artificial CTC blood samples. Clinical utility of the system was further validated. CTCs were detected in all the examined 36 patients with HCC, with an average of 14 +/- 10/2 mL. On the contrary, no CTCs were detected in healthy, benign liver disease or non-HCC cancer subjects. The current study also successfully demonstrated that the captured CTCs on our CTC-chip were readily released with ethylene diamine tetraacetic acid (EDTA); released CTCs remained alive and could be expanded to form a spheroid-like structure in a 3-dimensional cell culture assay; furthermore, sensitivity of released CTCs to chemotherapeutic agents (sorafenib or oxaliplatin) could be effectively tested utilizing this culture assay. In conclusion, the methodologies presented here offer great promise for accurate enumeration and easy release of captured CTCs, and released CTCs could be cultured for further functional studies. PMID- 27662380 TI - MicroRNA-33b Inhibits the Proliferation and Migration of Osteosarcoma Cells via Targeting Hypoxia-Inducible Factor-1alpha. AB - Recently, microRNA (miR)-33b has been demonstrated to act as a tumor suppressor in osteosarcoma. However, the regulatory mechanism of miR-33b in osteosarcoma cell proliferation and migration remains largely unknown. In this study, real time PCR showed that miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Its expression was also decreased in several common osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and migration. HIF 1alpha was further identified as a target of miR-33b, and its protein levels were reduced after overexpression of miR-33b in U2OS cells. Moreover, overexpression of HIF-1alpha significantly reversed the suppressive effect of miR-33b on U2OS cell proliferation and migration. In addition, HIF-1alpha was found to be significantly upregulated in osteosarcoma tissues compared to adjacent nontumor tissues, and their expression levels were inversely correlated to the miR-33b levels in osteosarcoma tissues. According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1alpha. Therefore, we suggest that the miR 33b/HIF-1alpha axis may become a promising therapeutic target for osteosarcoma. PMID- 27662379 TI - Implementation of a team-based learning course: Work required and perceptions of the teaching team. AB - BACKGROUND: Team-based learning was selected as a strategy to help engage pre registration undergraduate nursing students in a second-year evidence-informed decision making course. OBJECTIVES: To detail the preparatory work required to deliver a team-based learning course; and to explore the perceptions of the teaching team of their first experience using team-based learning. DESIGN: Descriptive evaluation. METHODS: Information was extracted from a checklist and process document developed by the course leader to document the work required prior to and during implementation. Members of the teaching team were interviewed by a research assistant at the end of the course using a structured interview schedule to explore perceptions of first time implementation. RESULTS: There were nine months between the time the decision was made to use team-based learning and the first day of the course. Approximately 60days were needed to reconfigure the course for team-based learning delivery, develop the knowledge and expertise of the teaching team, and develop and review the resources required for the students and the teaching team. This reduced to around 12days for the subsequent delivery. Interview data indicated that the teaching team were positive about team-based learning, felt prepared for the course delivery and did not identify any major problems during this first implementation. CONCLUSIONS: Implementation of team based learning required time and effort to prepare the course materials and the teaching team. The teaching team felt well prepared, were positive about using team-based learning and did not identify any major difficulties. PMID- 27662382 TI - Spine Injuries in Child Abuse. AB - BACKGROUND: Although rare, spinal injuries associated with abuse can have potentially devastating implications in the pediatric population. We analyzed the association of pediatric spine injury in abused children and determined the anatomic level of the spine affected, while also focusing on patient demographics, length of stay, and total hospital charges compared with spine patients without a diagnosis of abuse. METHODS: A retrospective review of the Kids' Inpatient Database was conducted from 2000 to 2012 to identify pediatric patients (below 18 y) who sustained vertebral column fractures or spinal cord injuries. Patients with a documented diagnosis of abuse were identified using ICD 9-CM diagnosis codes. Our statistical models consisted of multivariate linear regressions that were adjusted for age, race, and sex. RESULTS: There were 22,192 pediatric patients with a diagnosis of spinal cord or vertebral column injury during the study period, 116 (0.5%) of whom also had a documented diagnosis of abuse. The most common type of abuse was physical (75.9%). Compared with nonabused patients, abused patients were more likely to be below 2 years of age (OR=133.4; 95% CI, 89.5-198.8), female (OR=1.67; 95% CI, 1.16-2.41), and nonwhite (black: OR=3.86; 95% CI, 2.31-6.45; Hispanic: OR=2.86; 95% CI, 1.68-4.86; other: OR=2.33; 95% CI, 1.11-4.86). Abused patients also presented with an increased risk of thoracic (OR=2.57; 95% CI, 1.67-3.97) and lumbar (OR=1.67; 95% CI, 1.03 2.72) vertebral column fractures and had a multivariate-adjusted mean length of stay that was 62.2% longer (P<0.001) and mean total charges that were 52.9% higher (P<0.001) compared with nonabused patients. Furthermore, 19.7% of all pediatric spine patients under 2 years of age admitted during the study period belonged to the abused cohort. CONCLUSIONS: Spine injuries are rare but can be found in the pediatric population. With an additional documented diagnosis of abuse, these injuries affect younger patients in the thoracolumbar region of the spine, and lead to longer lengths of stay and higher hospital costs when compared with nonabused patients. Because of these findings, physicians should maintain a higher level of suspicion of abuse in patients with spine injuries, especially patients under 2 years of age. LEVEL OF EVIDENCE: Level III evidence-a case control study. PMID- 27662381 TI - Current Issues Affecting the Practice of Pediatric Orthopaedic Surgeons: Results of the 2014 Workforce Survey of American Academy of Pediatrics Section on Orthopaedics. AB - INTRODUCTION: The opinions of the pediatric orthopaedic workforce are shaped by market forces, regulatory processes, and local experience. The purpose of this report is to summarize the findings of the recent Workforce Survey of the American Academy of Pediatrics (AAP) Section on Orthopaedics (SOOr). This submission has been reviewed and approved by the Board of Directors of the Pediatric Orthopaedic Society of North America (POSNA). METHODS: In 2014, the AAP generated a survey to assess perceptions of pediatric orthopaedic surgeons about current issues that affect practice. The survey was sent to 856 POSNA and 141 AAP SOOr members. Responses were topically organized to report current workforce composition, practice patterns, and perceptions about electronic medical records (EMRs). RESULTS: Responses were collected from August to December, 2014, from 496 (50%) survey recipients including 83 of 141 (59%) AAP-SOOr members and 413 of 856 (48%) POSNA members. Analyses were restricted to the 397 respondents who reported that they are currently practicing pediatric orthopaedics. Nearly all of these (390/391, 100%) indicated that they provide direct patient care and work an average of 60 hours per week. Many (105/378, 28%) indicated that they would soon limit their practice or retire. A majority (299/394, 76%) indicated that they face competition in their geographic area, predominantly due to pediatric orthopaedic subspecialists (269/299, 90%). Major business changes had recently occurred or were anticipated by 21% of participants. Respondents reported that use of EMR makes them less efficient (252/397, 63%) and interferes with the patient-physician relationship (172/397, 43%). DISCUSSION: This workforce survey suggests that pediatric orthopaedic surgeons are concerned with challenges of competition despite concurrent increasing volume and complexity of referrals. External processes such as EMR changes are perceived to negatively impact practice efficiency and satisfaction. PMID- 27662383 TI - Graf Type-IV Hips Have a Higher Risk of Residual Acetabular Dysplasia at 1 Year of Age Following Successful Pavlik Harness Treatment for Developmental Hip Dysplasia. AB - BACKGROUND: We asked whether patient-specific factors and ultrasound (US) measurements of hip dysplasia severity at initial examination influence short term residual acetabular dysplasia in patients successfully treated with Pavlik harness for developmental hip dysplasia. METHODS: After IRB approval, 134 hips (84 patients) successfully treated by the Pavlik method between August 2011 and October 2014 with follow-up at 12 months of age were identified. Early successful treatment was defined as normal examination and US after approximately 12 weeks of Pavlik treatment. Multivariate linear and logistic regression models were used to identify factors associated with acetabular index (AI) measurements at 12 months as well as factors associated with an increase in AI between the 6- and 12 month timepoints (dysplastic progression). RESULTS: The study consisted of 134 hips (84 patients). The distribution of dysplastic, Barlow, and Ortolani hips was 44.8% (N=60), 30.6% (N=41), and 24.6% (N=33), respectively. The crude incidence of residual dysplasia at the 6-month visit (AI>30 degrees) was 11.7% (12/102). The incidence of residual dysplasia at the 12-month visit (AI>28 degrees) was 11.8% (13/111). Graf type was the only variable associated with AI values at the 12-month visit (mean difference: Graf type-IV-Other, 2.6; 95% confidence interval, 0.3-4.9; P=0.026). CONCLUSIONS: The risk of residual acetabular dysplasia after normal hip US following Pavlik treatment is not negligible. Radiographic surveillance is warranted to monitor and screen for dysplasia progression. Patients with dislocated Graf type-IV hips at diagnosis are at increased risk of residual acetabular dysplasia at 1 year after successful treatment with the Pavlik method. LEVEL OF EVIDENCE: Level III-therapeutic study. PMID- 27662384 TI - Prognosticating Factors of Relapse in Clubfoot Management by Ponseti Method. AB - BACKGROUND: It is challenging that some Ponseti method corrected clubfeet have a tendency to relapse. Controversies remain as to the implication of initial severity, representing the deformity degree, as well as number of casts needed, representing the treatment process, in predicting relapse. However, no study has been reported to take these 2 parameters into comprehensive consideration for outcome measurement. The purpose of this study is to investigate the correlation between the initial Pirani score and the number of casts required to correct the deformity in our series; to evaluate noncompliance as a risk factor of the deformity recurrence in Ponseti treatment; to test the validity and predictive value of a new proposed parameter, ratio of correction improvement (RCI) which is indicated by the initial Pirani scores divided by the number of casts. METHODS: A total of 116 consecutive patients with 172 idiopathic clubfeet managed by Ponseti method were followed prospectively for a minimum of 2 years from the start of brace wearing. RCI value and the other clinical parameters were studied in relation to the risk of relapse by using multivariate logistic regression analysis modeling. RESULTS: A positive correlation between the initial Pirani score and the number of casts required to correct the deformity was found in our series (r=0.67, P<0.01). There were 45 patients (39%) with brace noncompliance. The relapse rate was 49% (22/45). The odds ratio of relapse in noncompliant patients was 10 times more that in compliant patients (odds ratio=10.30 and 95% confidence interval, 2.69-39.42; P<0.01). The multivariate logistic regression analysis showed that there was significant association between relapse and RCI value. There were 42 patients (36%) with RCI value <1, among them, the relapse rate was 57% in 24 patients. The odds ratio of relapse in patients with RCI value <1 was 27 times more likely to relapse than those >1 (odds ratio=26.77 and 95% confidence interval, 5.70-125.72; P<0.01). CONCLUSIONS: On the basis of the findings from our study, we propose the RCI to be a new parameter in predicting the risk of relapse in Ponseti method of clubfoot management. Early intervention is recommended to optimize the brace compliance particularly in case with lower RCI value. LEVEL OF EVIDENCE: Level II-prognostic. PMID- 27662385 TI - Initial Experience With Percutaneous IM Rodding of the Humeri in Children With Osteogenesis Imperfecta. AB - BACKGROUND: To report a single-center surgical experience treating humeral deformity and fractures in children with osteogenesis imperfecta (OI) using the Fassier-Duval (FD) intramedullary elongating rods. METHODS: A retrospective review was conducted between December 2005 and July 2013 of all OI patients who underwent FD rodding with a minimum of 1-year follow-up. All patients were also being concurrently treated with bisphosphonates. RESULTS: Eighteen patients underwent internal fixation on a total of 35 humeri: 7 males and 11 females with an average age of 49 months. Thirty-five procedures were performed using FD rodding, with 5 utilizing only the male portion. Thirty procedures were primary FD implantation and 5 were revisions. Twelve patients had type III OI and 6 patients type IV OI. Indications for surgery included recurrent fracture, severe bowing deformity, and pain. Osteotomy methods included closed osteoclasis, percutaneous, or open osteotomies. Two patients required transfusions during their hospital stay. At our determined endpoint, 23 humeri (65.7%) had acceptable results with a mean follow-up time of 43 months (SD=27) with no revision. The remaining 12 humeri (34.3%) necessitated revision with a mean time to revision of 35 months (SD=29). Reasons for revision included: migration resulting in pain and functional difficulty (8.6%), migration with bowing (8.6%), and hardware failure secondary to trauma (8.6%). In addition, 2 revisions were required for nonunion (5.7%) and 1 for malunion (2.9%). To our knowledge, all other osteotomies performed during surgery resulted in bony union. CONCLUSIONS: The use of the FD system for correction of humeral deformity demonstrates a reasonable option to improve comfort and function in children with recurrent fractures and deformity secondary to OI. The FD system allows for decreased revision rates and less morbid instrumentation. LEVEL OF EVIDENCE: Level IV-retrospective case series. PMID- 27662386 TI - Capital Femoral Epiphyseal Extension May Confer Physeal Stability in Slipped Capital Femoral Epiphysis. AB - BACKGROUND: Factors including obesity and morphologic parameters around the hip that increase physeal stress are associated with an increased risk of slipped capital femoral epiphysis (SCFE). Recent evidence suggests that superior epiphyseal extension may confer stability to the physis and help protect against SCFE. The purpose of this study is to investigate the relationship between epiphyseal extension and SCFE using an age-matched and sex-matched cohort study. METHODS: We generated 2 separate cohorts for comparison: 89 patients with unilateral SCFE and 89 healthy subjects with no evidence of hip disease or deformity. We utilized the anterior-posterior and lateral films of the hip to measure the Southwick angle and the epiphyseal extension ratio (EER), defined as the ratio of extension of the capital femoral epiphysis down the femoral neck relative to the diameter of the femoral head. We then compared these measurements between cohorts and in subgroup analysis based on slip stability and whether subjects progressed to a contralateral slip. RESULTS: The SCFE cohort demonstrated a decreased superior epiphyseal extension ratio compared with control (superior EER 0.71 vs. 0.68, P=0.002). There was also a significant downward trend in superior EER from the control subjects (0.71+/-0.07) to the stable slips (0.69+/-0.06) to the unstable slips (0.65+/-0.04) with an overall difference between the groups (P=0.001). Eighteen of 44 (41%) subjects with unilateral stable slips and at least 6 months of follow-up went on to develop SCFE of the contralateral limb. The subjects who developed contralateral slips were younger (11.6+/-1.2 vs. 12.7+/-1.4 y, P=0.008); however, there was no difference in superior or anterior epiphyseal extension (P=0.75 and 0.23, respectively). There was no significant linear correlation between Southwick angle and superior or anterior EER (r=0.13 and 0.17, respectively, P>0.05 for both). CONCLUSIONS: Increasing capital femoral epiphyseal extension may confer physeal stability in the setting of SCFE. We propose that this epiphyseal extension reflects an adaptive response to limit physeal stress and reduce the risk for progression to SCFE. LEVEL OF EVIDENCE: Level III-prognostic study. PMID- 27662387 TI - Knee Arthritis in Children: When can be Safely Treated With Needle Joint Aspiration? A Large Children's Tertiary Hospital Study. AB - BACKGROUND: Early joint decompression associated to antibiotic therapy is the most important procedure to reduce joint damage in septic knee arthritis in children. Several joint decompression methods have been described such as arthrotomy with open debriding, arthroscopic drainage or needle joint aspiration. The aim of the present study was to determinate which patients with acute septic knee arthritis could be safely treated with needle joint aspiration. METHODS: Patients with an acute knee arthritis diagnosed between September 2003 and December 2013 in our children's tertiary hospital were retrospective review. All cases were initially treated with needle joint aspiration. Primary end-point was failure of joint aspiration. RESULTS: A total of 74 patients were included in the study. Forty-two (56.8%) were male and median age was 1.49 years. Mean delay between onset of symptoms and diagnosis was 3.6 days and in 25 (33.8%) cases patients needed more than 1 visit to the emergency room. Median C-reactive protein (CRP) value was 36.3 mg/L and was >20 mg/L in 59 (79.7%) cases. A total of 11 (14.9%) patients showed failure of the joint aspiration treatment between 3 and 21 days after initial joint aspiration. The stepwise forward logistic regression model only identified as independent predictor of joint aspiration failure an age older than 3 years old (odds ratio, 5.64; 95% confidence interval, 1.38-29.61; P=0.018). Joint aspiration did not fail in any patient younger than 12 months and neither in any patient younger than 3 years old with CRP value <20 mg/L. Otherwise, treatment failed in 38% of patients older than 3 years and in 16% of patients between 1 and 3 years with a CRP>20 mg/L. CONCLUSIONS: Septic knee arthritis treated with needle joint aspiration succeed in all patients younger than 1 year and in all patients between 1 and 3 years with a CRP<20 mg/L. Alternative treatment such as arthroscopy debridement should be early considered in patients older than 3 years and patients between 1 and 3 years with CRP>20 mg/L. LEVEL OF EVIDENCE: Level III. PMID- 27662388 TI - Spinal Instrumentation in Growing Children Retards the Natural Development of Pelvic Incidence. AB - BACKGROUND: Pelvic incidence increases gradually throughout growth until skeletal maturity. Growing rod instrumentation has been suggested to have a stabilizing effect on the development of the normal sagittal spinal alignment. The purpose of this study is to determine the effect of fixed sagittal plane caused by dual growing rod instrumentation on the natural progression of sagittal spinopelvic parameters in children with idiopathic or idiopathic-like early onset scoliosis. METHODS: Hospital records of children with growing rod instrumentation from 4 separate institutions were reviewed retrospectively. Inclusion criteria were idiopathic or idiopathic-like early onset scoliosis, treatment with dual growing rods with lower instrumented vertebra L4 or upper and more than 2 years of follow up. Instrumentation levels, magnitudes of major curve, thoracic kyphosis (T2 T12), lumbar lordosis (L1-S1) and pelvic incidence were recorded from preoperative and postoperative standing whole-spine radiographs. Estimated pelvic incidence was also calculated for each patient as if their spines had not been instrumented using the previous normative data. RESULTS: A total of 37 patients satisfied the inclusion criteria. Average age at initial surgery was 7.4+/-1.8 years (range, 4 to 12 y). Mean follow-up time was 71+/-26 months (range, 27 to 120 mo). Mean preoperative Cobb angle of 59+/-13.5 (range, 30 to 86) degrees was reduced to 35.1+/-17.5 (range, 11 to 78) degrees at the last follow-up. Mean preoperative T2-T12 kyphosis angle was 46.2+/-14.9 degrees (range, 22 to 84 degrees). At the latest follow-up, it was 44.8+/-16.2 degrees (range, 11 to 84 degrees) (P=0.93). Mean L1-S1 lordosis angle was 50.5+/-10.7 degrees (range, 30 to 72 degrees) preoperatively. At the latest follow-up, mean L1-S1 lordosis angle was 48.8+/-12.7 degrees (range, 26 to 74 degrees) (P=0.29). Mean preoperative pelvic incidence was 45.7+/-7.9 degrees (range, 30 to 68 degrees). At the latest follow-up, it was 46.7+/-8.4 degrees (range, 34 to 72 degrees) (P=0.303). The estimated average pelvic incidence was 49.5 degrees (P=0.012). CONCLUSIONS: Previously reported developmental changes of the sagittal spinal parameters were not observed in children who underwent posterior spinal instrumentation. Our findings suggest that spinal instrumentation impedes the natural development of the sagittal spinal profile. LEVEL OF EVIDENCE: Level IV-this is a retrospective case-series. PMID- 27662389 TI - Effects of Antibiotic Timing on Culture Results and Clinical Outcomes in Pediatric Musculoskeletal Infection. AB - INTRODUCTION: Musculoskeletal infection (MSI) is a common cause of morbidity and hospital resource utilization in the pediatric population. Many physicians prefer to withhold antibiotics until tissue cultures can be taken in an effort to improve culture yields. However, there is little evidence that this practice improves culture results or outcomes in pediatric MSI. Therefore, investigating the effects of antibiotic timing may lead to improved clinical practice guidelines for treating children with MSI. METHODS: An IRB-approved retrospective review was conducted that identified 113 patients aged 0 to 18 who presented to the pediatric emergency room at a tertiary care children's hospital with MSI from 2008 to 2013. Demographic data, culture results, severity markers, and intervention timing were obtained from the medical record. Logistic regression and Cox survival analysis were performed to determine the relationship of antibiotic timing with culture sensitivity and time to discharge. RESULTS: No difference was seen in culture sensitivity antibiotic administration in either the local (55% culture before antibiotics vs. 89% after antibiotics) or disseminated group (76% before vs. 79% after), which persisted when further accounting for disease severity with C-reactive protein. However, later administration of antibiotics in the local infection group correlated with a decreased likelihood of discharge (3.91 d when cultured before antibiotics vs. 2.93 d when cultured after antibiotics; hazard ratio, 0.53; P<0.05). In patients with disseminated infection, antibiotic administration was not shown to correlate with any difference in time to discharge (hazard ratio, 1.08). CONCLUSIONS: The authors were surprised to find that tissue culture sensitivities were not decreased by antibiotic administration in either local or disseminated MSI, suggesting that antibiotic administration should not be delayed to obtain tissue cultures. The correlation of earlier antibiotic administration with shorter length of stay in children with local MSI led the authors to conclude that antibiotics should be initiated as quickly as possible. Further study is necessary to confirm these findings and establish clinical practice guidelines. LEVEL OF EVIDENCE: Level III-retrospective cohort. PMID- 27662390 TI - Polychlorinated biphenyls and dibenzofurans increased abnormal sperm morphology without alterations in aneuploidy: The Yucheng study. AB - In 1979, more than 2000 persons ingested rice oil contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans; this event was called the "Yucheng accident." An increased percentage of oligospermia, reduced ability of sperm to penetrate oocytes, and reduced percentage of male offspring were reported in Yucheng men. This study examined whether the sperm sex ratio and chromosome aneuploidy are responsible for our observed findings in Yucheng men. In 1999-2000, Yucheng men and their neighborhood referents aged 37-50 years were recruited for physical examination, followed by semen analysis. The semen samples were analyzed for chromosomal aneuploidy through fluorescent in situ hybridization according to an established procedure in our laboratory. A total of 50 Yucheng men and 34 neighborhood referents volunteered to participate in the study. Although abnormal morphology was mildly increased, no differences were observed in sperm percentages, with normal numbers of chromosomes X, Y, and 8 in the two groups. The percentage of sperm with aneuploidy of the sex chromosomes or chromosome 8 and of that with diploidy did not vary between both groups. The normal X/Y sperm ratio was not different between the groups. However, among Yucheng men, 8% had a normal X/Y sperm ratio of >1.4, and no neighborhood referent showed such an elevated X/Y ratio. Chromosomal aneuploidy was not elevated in Yucheng men. The mechanisms underlying the reduced sperm capability of oocyte penetration and changed offspring sex ratio in Yucheng men remain undetermined. PMID- 27662392 TI - Influence of the coating level on the heterogeneous ozonolysis kinetics and product yields of chlorpyrifos ethyl adsorbed on sand particles. AB - Heterogeneous oxidation of chlorpyrifos ethyl (CLP) coated sand particles by gaseous ozone was studied. Mono-size sand was coated with CLP at different coating levels between 10 and 100 MUg g-1 and exposed to ozone. Results were analyzed thanks to Gas Surface Reaction and Surface Layer Reaction Models. Kinetic parameters derived from these models were analyzed and led to several conclusions. The equilibrium constant of O3 between the gas phase and the CLP coated sand was independent on the sand contamination level. Ozone seems to have similar affinity for coated or uncoated sand surface. Meanwhile, the kinetic parameters decreased with an increasing coating level. Chlorpyrifos Oxon, (CLPO) has been identified and quantified as an ozonolysis product. The product yield of CLPO remains constant (53 +/- 10%) for the different coating level. The key parameter influencing the CLP reactivity towards ozone was the CLP-coating level. This dependence had a great influence on the lifetime of the CLP coated on sand particles, with respect to ozone, which could reach several years at high contamination level. PMID- 27662391 TI - Preliminary analysis of allelochemicals produced by the diatom Phaeodactylum tricornutum. AB - Marine diatom Phaeodactylum tricornutum is known to exude allelochemicals with negative effects on Heterosigma akashiwo according to our previous study, while the information about the allelochemical compounds remains unknown. The present study dealt with isolation and analysis of the active substances released by P. tricornutum into the culture medium. Filtrate of P. tricornutum was extracted using ethyl acetate and chloroform respectively. The anti-algal fractions were isolated using high performance liquid chromatography (HPLC) and screened using activity-guided fraction methods. Results demonstrated that fraction II and VI showed significant allelopathic effect on H. akashiwo growth. Then the anti-algal activity fractions were analyzed preliminary using gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography-electrospray time of-flight mass spectrometry (HPLC-ESI-TOF-MS). An active compound was derived from fraction VI with the molecular weight of 578 and possible molecular formula of C30H38N6O6, which was speculated to be TYR-PRO-PHE-PRO-GLY-NH2. a kind of glycinamides. PMID- 27662393 TI - Measuring the cost implications of the Collaborative Accountable Care initiative in Texas. AB - OBJECTIVES: We analyzed changes in healthcare spending associated with the implementation of Cigna's Collaborative Accountable Care (CAC) initiative in a large multi-clinic physician practice. STUDY DESIGN: We compared claims from 2009, prior to the CAC initiative, against claims for 2010 to 2011, contrasting the patients covered by Cigna's CAC initiative with patients in other practices in the same geographic area covered by Cigna's medical plan. METHODS: We used a propensity weighted difference-in-differences approach, adjusting for age, sex, health status, and secular trends to isolate the treatment effect of the CAC. RESULTS: The CAC initiative resulted in a 5.7% reduction in net spending per patient for 2010 to 2011, relative to what spending would have been without the initiative. This reduced spending was evident in multiple service categories: evaluation and management, procedures, imaging, tests, and durable medical equipment. Professional payments, inpatient facility, and outpatient facility payments for Medical Clinic of North Texas enrollees all experienced significant cost savings relative to the control group. About half of the savings resulted from using lower-priced sources. CONCLUSIONS: The CAC initiative, which includes an embedded care coordinator and a list of recommended providers, was associated with cost savings similar to those reported by other initiatives, such as global budgets and risk-based contracts. PMID- 27662394 TI - Managing inappropriate requests of laboratory tests: from detection to monitoring. AB - OBJECTIVES: The main objectives of this study were to show a simple approach to detect inappropriate requests of laboratory tests and to monitor success after establishing interventions. These objectives were monitored through process and outcome indicators customized according to the type and phase of the appropriateness strategy. STUDY DESIGN: Quasi-experimental design. METHODS: Based on evidence regarding laboratory test utilization differences among different geographical areas of Spain, we identified serum calcium (s-Ca) testing to be underrequested and total bilirubin (tBil) testing to be overrequested in primary care patients who undergo testing at the Public University Hospital of San Juan, in San Juan de Alicante, Alicante, Spain. Additionally, the ratio of free thyroxine (FT4) tests to thyrotropin (also called thyroid-stimulating hormone [TSH]) tests was well above the published 0.25 goal in primary care. Finally, numerous laboratory tests were overrequested in hospitalized patients due to repetitive testing. We designed and implemented a variety of strategies to correct such inappropriateness and designed different indicators to monitor the intervention success over time. RESULTS: After implementation of the different strategies, the absolute number of s-Ca tests increased. The number of tBil tests in primary care, and numerous other tests repeated too frequently in hospitalized patients, decreased. The FT4/TSH indicator goal was reached and maintained over time. Regarding the outcome indicators, the strategy of reducing tBil tests in primary care and reducing the aggregate of unnecessary tests in hospitalized patients resulted in savings of $3543.80 and $9825.50, respectively, from January 2012 to December 2014. The s-Ca strategy, from November 2011 to December 2014, detected 62 subjects' primary hyperparathyroidism at a cost of $137.80 per case. CONCLUSIONS: The study demonstrates a simple approach to detect inappropriate requests of laboratory tests, and how to assess the potential success of interventions using process and outcome indicators. PMID- 27662396 TI - Mapping US commercial payers' coverage policies for medical interventions. AB - OBJECTIVES: To examine coverage policies for medical interventions issued by the largest US commercial payers. STUDY DESIGN: Review of publicly accessible coverage policies for medical interventions. METHODS: We categorized the 20 largest commercial payers' medical benefit coverage policies for medical technologies-current as of August 1, 2014-with respect to technology type (eg, medical devices, pharmaceuticals, surgeries). We identified the interventions most commonly subject to coverage policies and compared payer coverage determinations in terms of whether they covered the intervention and the evidence they reported reviewing. RESULTS: Eighteen payers made their coverage policies publicly available and 17 reported the evidence they reviewed in formulating policies. The types of technologies considered varied across payers, although most focused on devices and diagnostics. Of the 28 interventions most commonly subject to coverage policies, the coverage of 9 varied (ie, some payers covered the intervention and others did not). On average, payers reported reviewing clinical studies in 87% of coverage policies (range = 25%-100%). Two payers did not report reviewing systematic reviews or meta-analyses in any coverage policies, and 9 reported reviewing such evidence in at least half of their policies. Fourteen payers reported reviewing cost-effectiveness analyses at least some of the time, with frequency ranging from 8% to 43%. Commercial payers' coverage decisions did not appear to reflect direct input from patients or patient advocates, at least as stated in published coverage policies. CONCLUSIONS: Coverage of medical interventions varies across US private payers. Payers often report reviewing different evidence when formulating coverage policies, but do not report considering input directly from patients in evidence assessments. PMID- 27662395 TI - Knowledge gaps inhibit health IT development for coordinating complex patients' care. AB - OBJECTIVES: Complex patients incur a majority of healthcare costs in the United States, in part, because their care is poorly coordinated. We sought to determine the leading edge of health information technology (IT) tools for care coordination of complex patients. STUDY DESIGN: Qualitative discussions and technical expert panels. METHODS: We conducted 35 discussions with clinical leaders, technology and startup executives, government officials, academic researchers, and 2 technical expert panels. RESULTS: Although health IT has the potential to improve care coordination, the types of IT tools available to clinicians and patients are currently limited. We found substantial barriers to developing technical capabilities for improving care coordination, including lack of knowledge of users' needs; lack of standardized roles, responsibilities, and protocols; required changes in providers' work activities to achieve coordination; and an unclear value proposition. CONCLUSIONS: We found several innovative tools, but existing efforts suffer from important limitations, including minimal engagement by physicians, lack of standardized definitions of what the tools do, and challenges integrating with clinical workflows. For health IT to facilitate coordination of care for complex patients, user needs and workflows must be better understood and used to guide the development of technology and policy. PMID- 27662397 TI - Opportunities to improve the value of outpatient surgical care. AB - OBJECTIVES: Nearly 57 million outpatient surgeries-invasive procedures performed on an outpatient basis in hospital outpatient departments (HOPDs) or ambulatory surgery centers (ASCs)-produced annually in the United States account for roughly 7% of healthcare expenditures. Although moving inpatient surgeries to outpatient settings has lowered the cost of care, substantial opportunities to improve the value of outpatient surgery remain. To exploit these remaining opportunities, we composed an evidence-based care delivery composite for national discussion and pilot testing. STUDY DESIGN: Evidence-based care delivery composite. METHODS: We synthesized peer-reviewed publications describing efforts to improve the value of outpatient surgical care, interviewed patients and clinicians to understand their most deeply felt discontents, reviewed potentially relevant emerging science and technology, and observed surgeries at healthcare organizations nominated by researchers as exemplars of efficiency and effectiveness. Primed by this information, we iterated potential new designs utilizing criticism from practicing clinicians, health services researchers, and healthcare managers. RESULTS: We found that 3 opportunities are most likely to improve value: 1) maximizing the appropriate use of surgeries via decision aids, clinical decision support, and a remote surgical coach for physicians considering a surgical referral; 2) safely shifting surgeries from HOPDs to high-volume, multi-specialty ASCs where costs are much lower; and 3) standardizing processes in ASCs from referral to recovery. CONCLUSIONS: Extrapolation based on published studies of the effects of each component suggests that the proposed 3-part composite may lower annual national outpatient surgical spending by as much as one-fifth, while maintaining or improving outcomes and the care experience for patients and clinicians. Pilot testing and evaluation will allow refinement of this composite. PMID- 27662398 TI - Body mass index and the risk of cancer in women compared with men: a meta analysis of prospective cohort studies. AB - Studies investigating the association between BMI and the risk of the common cancers in men or women have reported inconsistent results. We searched the PubMed, Embase, and Cochrane Library electronic databases for relevant articles published until April 2015. Overall, we analyzed 128 datasets (51 articles), including 154 939 incident cancer cases. The pooled relative risk ratio (RRR) (female to male) showed that the relative risk of overweight associated with colorectal [RRR: 0.91; 95% confidence interval (CI): 0.85-0.97] or rectal cancer (RRR: 0.94; 95% CI: 0.88-0.99) was significantly lower in women than in men. However, the relative risk of overweight associated with lung (RRR: 1.14; 95% CI: 1.06-1.22) or kidney cancer (RRR: 1.15; 95% CI: 1.05-1.26) was significantly higher in women than in men. Furthermore, the relative risk of obesity associated with liver (RRR: 0.71; 95% CI: 0.51-0.99), colorectal (RRR: 0.83; 95% CI: 0.75 0.93), colon (RRR: 0.73; 95% CI: 0.68-0.0.78), rectal (RRR: 0.84; 95% CI: 0.76 0.92), and kidney cancer (RRR: 1.20; 95% CI: 1.06-1.37) differed significantly between women and men. Finally, the relative risk of underweight associated with gastric (RRR: 0.83; 95% CI: 0.70-0.97), liver (RRR: 0.83; 95% CI: 0.71-0.97), and gallbladder cancer (RRR: 1.25; 95% CI: 1.04-1.49) differed significantly according to sex. In conclusion, our study showed that the association between BMI and the risk of several cancers was significantly different between the sexes. For some cancer types, the sex difference was affected by country, sample size, follow-up duration, and study quality. PMID- 27662399 TI - Quality of Quality Measurement: Impact of Risk Adjustment, Hospital Volume, and Hospital Performance. AB - BACKGROUND: The validity of basing healthcare reimbursement policy on pay-for performance is grounded in the accuracy of performance measurement. METHODS: Monte Carlo simulation was used to examine the accuracy of performance profiling as a function of statistical methodology, case volume, and the extent to which hospital or physician performance deviates from the average. RESULTS: There is extensive variation in the true-positive rate and false discovery rate as a function of model specification, hospital quality, and hospital case volume. Hierarchical and nonhierarchical modeling are both highly accurate at very high case volumes for very low-quality hospitals. At equivalent case volumes and hospital effect sizes, the true-positive rate is higher for nonhierarchical modeling than for hierarchical modeling, but the false discovery rate is generally much lower for hierarchical modeling than for nonhierarchical modeling. At low hospital case volumes (200) that are typical for many procedures, and for hospitals with twice the rate of death or major complications for patients undergoing isolated coronary artery bypass graft surgery at the average hospital, hierarchical modeling missed 90.6% of low-quality hospitals, whereas nonhierarchical modeling missed 65.3%. However, at low case volumes, 38.9% of hospitals classified as low-quality outliers using nonhierarchical modeling were actually average quality, compared to 5.3% using hierarchical modeling. CONCLUSIONS: Nonhierarchical modeling frequently misclassified average-quality hospitals as low quality. Hierarchical modeling commonly misclassified low quality hospitals as average. Assuming that the consequences of misclassifying an average-quality hospital as low quality outweigh the consequences of misclassifying a low-quality hospital as average, hierarchical modeling may be the better choice for quality measurement. PMID- 27662400 TI - Do Not Use Hierarchical Logistic Regression Models with Low-incidence Outcome Data to Compare Anesthesiologists in Your Department. PMID- 27662401 TI - Neurosteroid Allopregnanolone Suppresses Median Nerve Injury-induced Mechanical Hypersensitivity and Glial Extracellular Signal-regulated Kinase Activation through gamma-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus. AB - BACKGROUND: Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. METHODS: We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of gamma-aminobutyric acid type A receptor antagonist (bicuculline) or gamma-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI induced behavioral hypersensitivity. RESULTS: At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury induced behavioral hypersensitivity (withdrawal threshold [mean +/- SD], 7.4 +/- 1.1, 8.7 +/- 1.0, and 10.3 +/- 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. CONCLUSIONS: Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via gamma-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy. PMID- 27662402 TI - Accelerating flow propagator measurements for the investigation of reactive transport in porous media. AB - NMR propagator measurements are widely used for identifying the distribution of molecular displacements over a given observation time, characterising a flowing system. However, where high q-space resolution is required, the experiments are time consuming and therefore unsuited to the study of dynamic systems. Here, it is shown that with an appropriately sampled subset of the q-space points in a high-resolution flow propagator measurement, one can quickly and robustly reconstruct the fully sampled propagator through interpolation of the acquired raw data. It was found that exponentially sampling ~4% of the original data points allowed a reconstruction with the deviation from the fully sampled propagator below the noise level, in this case reducing the required experimental time from ~2.8h to <7min. As a demonstration, this approach is applied to observe the temporal evolution of the reactive flow of acid through an Estaillades rock core plug. It is shown that 'wormhole' formation in the rock core plug provides a channel for liquid flow such that the remaining pore space is by-passed, thereby causing the flow velocity of the liquid in the remaining part of the plug to become stagnant. The propagator measurements are supported by both 1D profiles and 2D imaging data. Such insights are of importance in understanding well acidisation and CO2 sequestration processes. PMID- 27662403 TI - Reduction of variance in measurements of average metabolite concentration in anatomically-defined brain regions. AB - Multiple methods have been proposed for using Magnetic Resonance Spectroscopy Imaging (MRSI) to measure representative metabolite concentrations of anatomically-defined brain regions. Generally these methods require spectral analysis, quantitation of the signal, and reconciliation with anatomical brain regions. However, to simplify processing pipelines, it is practical to only include those corrections that significantly improve data quality. Of particular importance for cross-sectional studies is knowledge about how much each correction lowers the inter-subject variance of the measurement, thereby increasing statistical power. Here we use a data set of 72 subjects to calculate the reduction in inter-subject variance produced by several corrections that are commonly used to process MRSI data. Our results demonstrate that significant reductions of variance can be achieved by performing water scaling, accounting for tissue type, and integrating MRSI data over anatomical regions rather than simply assigning MRSI voxels with anatomical region labels. PMID- 27662404 TI - Is there any difference in Amide and NOE CEST effects between white and gray matter at 7T? AB - Measurement of Chemical Exchange Saturation Transfer (CEST) is providing tissue physiology dependent contrast, e.g. by looking at Amide and NOE (Nuclear Overhauser Enhancement) effects. CEST is unique in providing quantitative metabolite information at high imaging resolution. However, direct comparison of Amide and NOE effects between different tissues may result in wrong conclusions on the metabolite concentration due to the additional contributors to the observed CEST contrast, such as water content (WC) and water T1 relaxation (T1w). For instance, there are multiple contradictory reports in the literature on Amide and NOE effects in white matter (WM) and gray matter (GM) at 7T. This study shows that at 7T, tissue water T1 relaxation is a stronger contributor to CEST contrasts than WC. After water T1 correction, there was no difference in Amide effects between WM and GM, whereas WM/GM contrast was enhanced for NOE effects. PMID- 27662405 TI - Fully Printed and Encapsulated SWCNT-Based Thin Film Transistors via a Combination of R2R Gravure and Inkjet Printing. AB - Fully printed thin film transistors (TFT) based on poly(9,9-di-n-dodecylfluorene) (PFDD) wrapped semiconducting single walled carbon nanotube (SWCNT) channels are fabricated by a practical route that combines roll-to-roll (R2R) gravure and ink jet printing. SWCNT network density is easily controlled via ink formulation (concentration and polymer:CNT ratio) and jetting conditions (droplet size, drop spacing, and number of printed layers). Optimum inkjet printing conditions are established on Si/SiO2 in which an ink consisting of 6:1 PFDD:SWCNT ratio with 50 mg L-1 SWCNT concentration printed at a drop spacing of 20 MUm results in TFTs with mobilities of ~25 cm2 V-1 s-1 and on-/off-current ratios > 105. These conditions yield excellent network uniformity and are used in a fully additive process to fabricate fully printed TFTs on PET substrates with mobility values > 5 cm2 V-1 s-1 (R2R printed gate electrode and dielectric; inkjet printed channel and source/drain electrodes). An inkjet printed encapsulation layer completes the TFT process (fabricated in bottom gate, top contact TFT configuration) and provides mobilities > 1 cm2 V-1 s-1 with good operational stability, based on the performance of an inverter circuit. An array of 20 TFTs shows that most have less than 10% variability in terms of threshold voltage, transconductance, on-current, and subthreshold swing. PMID- 27662406 TI - Synthetic Access to All Four Stereoisomers of Oxetin. AB - A short synthesis of all four stereoisomers of 3-amino-2-oxetanecarboxylic acid (oxetin) is described. The oxetane core is built using a Paterno-Buchi photochemical [2 + 2] cycloaddition; from the key intermediates, complementary resolution protocols provide access to enantiomerically pure oxetin and epi oxetin on gram-scale. PMID- 27662408 TI - DELAYED-ONSET BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION ASSOCIATED WITH GASTRIC ADENOCARCINOMA. AB - PURPOSE: To report an unusual case of delayed-onset bilateral diffuse uveal melanocytic proliferation in a patient with a remote history of gastric adenocarcinoma 17 years earlier. METHODS: Case report of a patient with bilateral diffuse uveal melanocytic proliferation including comprehensive systemic and ocular examinations. RESULTS: A 78-year-old man presented with a history of progressive bilateral vision loss during the 4 previous years associated with fever of unknown origin. He underwent total gastrectomy 17 years earlier as a treatment for gastric adenocarcinoma. Funduscopic examination revealed multiple subretinal pigmented and nonpigmented lesions involving the posterior pole of both eyes. These lesions showed early hyperfluorescence on fluorescein angiography, producing a giraffe pattern. Spectral-domain optical coherence tomography showed intraretinal and subretinal fluid with multiple hyperreflective mounds involving the retinal pigment epithelium. Treatment with the intravitreal anti-vascular endothelial growth factor agent, ranibizumab, produced anatomical improvement in both eyes but visual improvement in just the right eye. CONCLUSION: Although delayed-onset bilateral diffuse uveal melanocytic proliferation may occur, it is important to rule out a second malignancy. To the knowledge of the authors, this is the first report of delayed-onset bilateral diffuse uveal melanocytic proliferation associated with gastric adenocarcinoma. Treatment with intravitreal anti-vascular endothelial growth factor therapy warrants further evaluation. PMID- 27662407 TI - Modeling HIV vaccine trials of the future. AB - PURPOSE OF REVIEW: Models of implementation of known-effective interventions for HIV prevention indicate that an efficacious vaccine to prevent HIV infection would be critical for controlling the HIV pandemic. Key issues in the design of future HIV vaccine trials are: first, how to develop reliable immunological correlates of vaccine efficacy, second, how to down-select candidate vaccine regimens into efficacy trials, and third, how to learn about vaccine efficacy in the context of the evolving HIV prevention landscape. RECENT FINDINGS: Whereas in the past phase-I/-II HIV vaccine trials have addressed the first and second points using a small set of immunological assays and readouts, recently they have used a battery of assays with highly multivariate readouts. In addition, systems vaccinology studies of other pathogens measuring PBMC transcriptomics and other immunological features pre- and postfirst vaccination are demonstrating value, for example, providing discoveries that preimmunization and early postimmunization cell population markers can predict the influenza-specific antibody titer that is a correlate of vaccine protection. The HIV prevention landscape continues to evolve, and the design and analysis of vaccine trials is evolving alongside, to accommodate increasingly dynamic and regional standards of HIV prevention. SUMMARY: Development of interpretable and robust functional assays, in addition to the associated bioinformatics and statistical analytic tools, is needed to improve the assessment of correlates of protection in efficacy trials and the down-selection of candidate vaccine regimens into efficacy trials. Moreover, high-priority trials should integrate systems vaccinology, including the analysis of prevaccination and early postvaccination markers. PMID- 27662409 TI - SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY VALIDATES LAMINA CRIBROSA ANOMALY IN OPTIC DISK PIT. AB - PURPOSE: Swept Source Optical Coherence Tomography validates lamina cribrosa anomaly in optic disk pit. METHOD: Observational case report. RESULTS: A 25-year old African American male presented with decreased vision in right eye of 4 days duration. Best corrected visual acuity (BCVA) for distance in right eye was 20/200 and in left eye was 20/20. Dilated fundus examination of right eye showed serous macular detachment of entire posterior pole along with an optic pit on temporal margin of optic disk. En-face image of the optic disk on Swept source OCT (SS-OCT) confirmed defect in the lamina cribrosa in the right eye. CONCLUSION: Congenital optic disk pit a birth defect in lamina cribrosa is a rare, visually impairing disorder. Spectral domain optical coherence tomography (SD-OCT) scan showed neurosensory detachment, however, lamina cribrosa defects are not delineated with it. SS-OCT a recent advance in scanning technology allows superior resolution of optic disk and confirms the anomaly of lamina cribrosa. PMID- 27662410 TI - High Throughput Light Absorber Discovery, Part 1: An Algorithm for Automated Tauc Analysis. AB - High-throughput experimentation provides efficient mapping of composition property relationships, and its implementation for the discovery of optical materials enables advancements in solar energy and other technologies. In a high throughput pipeline, automated data processing algorithms are often required to match experimental throughput, and we present an automated Tauc analysis algorithm for estimating band gap energies from optical spectroscopy data. The algorithm mimics the judgment of an expert scientist, which is demonstrated through its application to a variety of high throughput spectroscopy data, including the identification of indirect or direct band gaps in Fe2O3, Cu2V2O7, and BiVO4. The applicability of the algorithm to estimate a range of band gap energies for various materials is demonstrated by a comparison of direct-allowed band gaps estimated by expert scientists and by automated algorithm for 60 optical spectra. PMID- 27662411 TI - Conical-Intersection Topographies Suggest That Ribose Exhibits Enhanced UV Photostability. AB - Carbohydrates are essential building blocks of life that assume a multitude of biological functions in all living organisms found on Earth. It was recently reported that ribose was identified in UV-irradiated interstellar ice analogs, which suggests that it can be found on comets and that it may have been transported to Earth via the impact of comets. Herein, we present computational results obtained with multiconfigurational ab initio quantum-chemical methods showing that various photochemical processes for radiationless deactivation are available for photoexcited ribose. These processes are driven by nsigma* states and involve either O-H- or endocyclic or exocyclic C-O-bond elongation whereby a conical intersection with the electronic ground state becomes accessible. The local topography of the potential-energy surfaces around these conical intersections suggests that these intersections mediate efficient radiationless deactivation and favor regeneration of the initially photoexcited ground-state reactant. These findings indicate that ribose found in interstellar space can be expected to be highly photostable upon irradiation with UV starlight, which could be of relevance in the field of astrobiology. PMID- 27662412 TI - Photocatalytic Oxidation of Lignin Model Systems by Merging Visible-Light Photoredox and Palladium Catalysis. AB - Lignin valorization has long been recognized as a sustainable solution for the renewable production of aromatic compounds. Two-step oxidation/reduction strategies, whereby the first oxidation step is required to "activate" lignin systems for controlled fragmentation reactions, have recently emerged as viable routes toward this goal. Herein we describe a catalytic protocol for oxidation of lignin model systems by combining photoredox and Pd catalysis. The developed dual catalytic protocol allowed the efficient oxidation of lignin model substrates at room temperature to afford the oxidized products in good to excellent yields. PMID- 27662414 TI - On the shoulders of giants. PMID- 27662413 TI - Quantitative in Situ Analysis of Ionomer Structure in Fuel Cell Catalytic Layers. AB - A quantitative in situ investigation of the structure of the catalytic layer of polymer electrolyte membrane fuel cells using material-sensitive and conductive atomic force microscopy is reported. The distribution and size of the ionomer phase at the surface of the catalytic layer is retrieved from adhesion force mappings, measured at high humidity and up to 75 degrees C. The average ionomer layer thickness varies between 7 and 13 nm for three differently prepared samples, as concluded from the histograms. Evidence of a lamellar structure of the thinner ionomer layers is presented. A significant thinning of the ionomer layers after long-term fuel cell operation is observed. PMID- 27662415 TI - A blessing and a curse: is high NK cell activity good for health and bad for reproduction? AB - Few topics in recent reproductive medicine have been the subject of as much controversy, media attention and passionate debate as natural killer (NK) cells and their role in reproductive failure. The question of whether elevated NK cell levels are a cause of infertility and pregnancy loss, and whether they provide a potential target for therapy to improve reproductive outcomes, lacks a definitive answer. It is clear, however, that a significant number of women with reproductive failure have abnormal NK cell parameters reflecting high immunological activity. Amongst all the debate, the wider implications of NK cell overactivity - and attempts to suppress it - have not yet been considered. The literature suggests that although elevated NK cell activity may not be conducive to reproduction, it could in fact be beneficial in other areas of health and disease such as cancer and infection. Further research is needed to determine whether this hypothesis holds true in women with NK cell-related reproductive failure. PMID- 27662416 TI - GnRH agonist trigger with intensive luteal phase support vs. human chorionic gonadotropin trigger in high responders: an observational study reporting pregnancy outcomes and incidence of ovarian hyperstimulation syndrome. AB - A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had >=18 follicles >=11mm or serum oestradiol >18,000pmol/l on the day of trigger. Patients had a single or double embryo transfer at cleavage or blastocyst stage. Logistic regression was used to adjust for differences between the groups. An intention-to-treat analysis of all cycles was performed. No statistically significant differences were observed in terms of positive pregnancy test, clinical pregnancy rate and live birth rate. Only one patient (0.3%) was hospitalized with severe OHSS in the GnRHa group, compared to 26 patients (13%) in the hCG group. In conclusion, GnRHa trigger is associated with similar pregnancy rates with hCG trigger and a significant reduction in hospitalization for severe OHSS after an intention to treat analysis was performed. PMID- 27662417 TI - Cohort study of perinatal outcomes of children born following surgical sperm recovery. AB - There is a relative paucity of data on perinatal outcomes following Intracytoplasmic Sperm Injection using surgically retrieved sperm. In this retrospective cohort study, data were collected on couples who conceived following Intracytoplasmic Sperm Injection using surgically retrieved sperm from 1996 to 2014. Outcome measures included live birth, miscarriage, congenital abnormality, birthweight, gestation at delivery, stillbirth and neonatal death. Outcome measures were compared according to male diagnosis and sperm source. Live birth rates were similar between groups (obstructive azoospermia 90%, non obstructive azoospermia 83%, p = 0.55). There was a trend towards higher miscarriage rates in the non-obstructive azoospermia group (17% versus 9%, p = 0.45). Other perinatal outcomes were similar between groups. In those with obstructive azoospermia, live birth rates were similar regardless of source of sperm (epididymal 89%, testicular 91%, p = 0.79). Median gestation at delivery was earlier in the epididymal sperm group (39 weeks versus 40 weeks, p = 0.02). Other perinatal outcomes were unaffected by sperm source. Overall these results are reassuring, suggesting high live birth rates regardless of diagnosis or sperm source, although there may be higher miscarriage rates in cases of non obstructive azoospermia. Other perinatal outcomes were not affected by diagnosis or sperm source. PMID- 27662418 TI - Elevations on select Conners' CPT-II scales indicate noncredible responding in adults with traumatic brain injury. AB - Elevations on certain Conners' CPT-II scales are known to be associated with invalid responding. However, scales and cutoffs vary across studies. In addition, the methodology behind developing performance validity tests (PVTs) has been challenged for mistaking true impairment for noncredible presentation. Using ability-based tests as a PVT makes clinicians especially vulnerable to this criticism. The present study examined the ability of CPT-II to dissociate effort from impairment in 47 adults clinically referred for neuropsychological assessment. CPT-II scales previously identified as PVTs (Omissions, Commissions, Hit Reaction Time SE, Variability, and Perseverations) produced classification accuracies hovering around .50 sensitivity at .90 specificity. The subsample that failed these PVTs performed within normal range on other tests of working memory, processing speed, visual attention, and executive function. Results suggest that the select CPT-II based PVTs are sensitive to invalid responding, and are associated with depression and anxiety, but are unrelated to cognitive functioning. PMID- 27662420 TI - Room-Temperature Phosphorescence of Crystalline Metal-Free Organoboron Complex. AB - The photoluminescence (PL) properties of a metal-free organoboron complex, bis(4 iodobenzoyl)methanatoboron difluoride (1BF2 ), were elucidated. At room temperature, 1BF2 emits blue fluorescence (FL) in nBuCl upon photoexcitation. In contrast, crystals of 1BF2 emit green PL comprised of FL and phosphorescence (PH). The room-temperature PH of crystalline 1BF2 is a consequence of 1) suppression of thermal deactivation of the S1 and T1 excited states and 2) enhancement of intersystem crossing (ISC) from the S1 to T2 or T1 . The results of X-ray crystallographic and theoretical studies supported the proposal that the former (1) is a result of intermolecular interactions caused by pi-stacking in the rigid crystal packing structure of 1BF2 . The latter (2) is an effect of not only the heavy-atom effect of iodine, but also the continuous pi-stacking alignment of 1BF2 molecules in crystals, which leads to a forbidden S1 ->S0 transition and a small energy gap between the S1 and T2 or T1 . PMID- 27662419 TI - Depressive Symptoms and Perceptions of Child Difficulty Are Associated with Less Responsive Feeding Behaviors in an Observational Study of Low-Income Mothers. AB - BACKGROUND: Maternal depressive symptoms and perceptions of child difficulty are associated with negative effects on general development and cognitive functioning in children. The study examined associations between maternal depressive symptoms, perceptions of child difficulty, and maternal feeding behaviors in a population at elevated risk for childhood obesity. METHODS: Participants were 138 low-income black and Hispanic mothers and their children (ages 3-5) participating in an observational study of mealtimes among Head Start families. Three dinnertime observations were conducted over 2 weeks on each family and audio/videotaped for coding. Coding included eating influence attempts and other food- and nonfood-related interactions exhibited by the mother during dinner. Mothers completed questionnaires on depressive symptoms and perceptions of child difficulty. Linear regressions were conducted, examining associations between maternal depressive symptoms, perceptions of child difficulty, and coded parent feeding behaviors. RESULTS: Mothers reporting higher levels of depressive symptoms used more verbal pressure to get their child to eat during meals, were more likely to discourage child independence, and less likely to enforce table manners. Mothers reporting higher perceptions of child difficulty were less likely to have nonfood-related discussions during meals and to try to get the child to eat a different food. CONCLUSIONS: This study is one of the first to investigate associations between maternal depression, perceptions of child difficulty, and mother's feeding behaviors during meals using observational methodology. These results may help researchers identify specific parental characteristics and feeding practices on which to intervene when developing tailored intervention programs for reducing childhood obesity. PMID- 27662421 TI - Wound signaling: The missing link in plant regeneration. AB - Wounding is the first event that occurs in plant regeneration. However, wound signaling in plant regeneration is barely understood. Using a simple system of de novo root organogenesis from Arabidopsis thaliana leaf explants, we analyzed the genes downstream of wound signaling. Leaf explants may produce at least two kinds of wound signals to trigger short-term and long-term wound signaling. Short-term wound signaling is primarily involved in controlling auxin behavior and the fate transition of regeneration-competent cells, while long-term wound signaling mainly modulates the cellular environment at the wound site and maintains the auxin level in regeneration-competent cells. YUCCA (YUC) genes, which are involved in auxin biogenesis, are targets of short-term wound signaling in mesophyll cells and of long-term wound signaling in regeneration-competent cells. The expression patterns of YUCs provide important information about the molecular basis of wound signaling in plant regeneration. PMID- 27662422 TI - Anti-Tumor Effects of Cardiac Glycosides on Human Lung Cancer Cells and Lung Tumorspheres. AB - Lung cancer is a leading cause of cancer-related death in the United States. Although several drugs have been developed that target individual biomarkers, their success has been limited due to intrinsic or acquired resistance for the specific targets of such drugs. A more effective approach is to target multiple pathways that dictate cancer progression. Cardiac glycosides demonstrate such multimodal effects on cancer cell survival, and our aim was to evaluate the effect of two naturally occurring monosaccaridic cardiac glycosides-Convallatoxin and Peruvoside on lung cancer cells. Although both drugs had significant anti proliferative effects on H460 and Calu-3 lung cancer cells, Convallatoxin demonstrated twofold higher activity as compared to Peruvoside using both viability and colony forming assays, suggesting a role for the aglycone region in dictating drug potency. The tumor suppressor p53 was found to be important for action of both drugs-p53-underexpressing cells were less sensitive as compared to p53-positive H460 cells. Further, assessment of p53-underexpressing H460 cells showed that drugs were able to arrest cells in the G0/G1 phase of the cell cycle in a dose-dependent manner. Both drugs significantly inhibited migration and invasion of cancer cells and decreased the viability of floating tumorspheres. An assessment of intracellular pathways indicated that both drugs were able to modulate proteins that are involved in apoptosis, autophagy, cell cycle, proliferation, and EMT. Our data suggest, a promising role for cardiac glycosides in lung cancer treatment, and provides impetus for further investigation of the anti-cancer potential of this class of drugs. J. Cell. Physiol. 232: 2497-2507, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662423 TI - Additive Technology: Update on Current Materials and Applications in Dentistry. AB - Additive manufacturing or 3D printing is becoming an alternative to subtractive manufacturing or milling in the area of computer-aided manufacturing. Research on material for use in additive manufacturing is ongoing, and a wide variety of materials are being used or developed for use in dentistry. Some materials, however, such as cobalt chromium, still lack sufficient research to allow definite conclusions about the suitability of their use in clinical dental practice. Despite this, due to the wide variety of machines that use additive manufacturing, there is much more flexibility in the build material and geometry when building structures compared with subtractive manufacturing. Overall additive manufacturing produces little material waste and is energy efficient when compared to subtractive manufacturing, due to passivity and the additive layering nature of the build process. Such features make the technique suitable to be used with fabricating structures out of hard to handle materials such as cobalt chromium. The main limitations of this technology include the appearance of steps due to layering of material and difficulty in fabricating certain material generally used in dentistry for use in 3D printing such as ceramics. The current pace of technological development, however, promises exciting possibilities. PMID- 27662424 TI - The infectious disease blood safety risk of Australian hemochromatosis donations. AB - BACKGROUND: It has been suggested that blood donors with hereditary hemochromatosis may pose an increased infectious disease risk and adversely affect recipient outcomes. This study compares the infectious disease risk of whole blood (WB) donors enrolled as therapeutic (T) donors to voluntary WB donors to evaluate the safety of blood products provided by the T donors. STUDY DESIGN AND METHODS: This was a retrospective cohort study of all WB donations at the Australian Red Cross Blood Service who donated between January 1, 2011, and December 31, 2013, comparing a yearly mean of 11,789 T donors with 107,773 total donations and a yearly mean of 468,889 voluntary WB donors with 2,584,705 total donations. We compared postdonation notification of infectious illnesses, bacterial contamination screening results, and positive tests for blood borne viruses in T and WB donors. RESULTS: Rates of transfusion-transmissible infections in donations destined for component manufacture were significantly lower in therapeutic donations compared to voluntary donations (8.4 vs. 21.6 per 100,000 donations). Bacterial contamination (43.0 vs. 45.9 per 100,000 donations) and postdonation illness reporting (136.2 vs. 110.8 per 100,000 donations) were similar in both cohorts. CONCLUSIONS: The Australian therapeutic venisection program enables T donors to provide a safe and acceptable source of donated WB that has a low infectious disease risk profile. PMID- 27662426 TI - Facile Synthesis of Platinum-Cerium(IV) Oxide Hybrids Arched on Reduced Graphene Oxide Catalyst in Reverse Micelles with High Activity and Durability for Hydrolysis of Ammonia Borane. AB - Highly dispersed Pt-CeO2 hybrids arched on reduced graphene oxide (Pt-CeO2 /rGO) were facilely synthesized by a combination of the reverse micelle technique and a redox reaction without any additional reductant or surfactant. Under a N2 atmosphere, the redox reaction between Ce3+ and Pt2+ occurs automatically in alkaline solution, which results in the formation of Pt-CeO2 /rGO nanocomposites (NCs). The as-synthesized Pt-CeO2 /rGO NCs exhibit superior catalytic performance relative to that shown by the free Pt nanoparticles, Pt/rGO, Pt-CeO2 hybrid, and the physical mixture of Pt-CeO2 and rGO; furthermore, the nanocomposites show significantly better activity than the commercial Pt/C catalyst toward the hydrolysis of ammonia borane (NH3 BH3 ) at room temperature. Moreover, the Pt CeO2 /rGO NCs have remarkable stability, and 92 % of their initial catalytic activity is preserved even after 10 runs. The excellent activity of the Pt-CeO2 /rGO NCs can be attributed not only to the synergistic structure but also to the electronic effects of the Pt-CeO2 /rGO NCs among Pt, CeO2 , and rGO. PMID- 27662425 TI - The effects of cognitive load during intertrial intervals on judgements of control: The role of working memory and contextual learning. AB - When there is no contingency between actions and outcomes, but outcomes occur frequently, people tend to judge that they have control over those outcomes, a phenomenon known as the outcome density (OD) effect. Recent studies show that the OD effect depends on the duration of the temporal interval between action-outcome conjunctions, with longer intervals inducing stronger effects. However, under some circumstances OD effect is reduced, for example when participants are mildly depressed. We reasoned that working memory (WM) plays an important role in learning of context; with reduced WM capacity to process contextual information during intertrial intervals (ITIs) during contingency learning might lead to reduced OD effects (limited capacity hypothesis). To test this, we used a novel dual-task procedure that increases the WM load during the ITIs of an operant (e.g., action-outcome) contingency learning task to impact contextual learning. We tested our hypotheses in groups of students with zero (Experiments 1, N=34), and positive contingencies (Experiment 2, N=34). The findings indicated that WM load during the ITIs reduced the OD effects compared to no load conditions (Experiment 1 and 2). In Experiment 2, we observed reduced OD effects on action judgements under high load in zero and positive contingencies. However, the participants' judgements were still sensitive to the difference between zero and positive contingencies. We discuss the implications of our findings for the effects of depression and context in contingency learning. PMID- 27662427 TI - Distinguishing contemporary hybridization from past introgression with postgenomic ancestry-informative SNPs in strongly differentiated Ciona species. AB - Biological introductions bring into contact species that can still hybridize. The evolutionary outcomes of such secondary contacts may be diverse (e.g. adaptive introgression from or into the introduced species) but are not yet well examined in the wild. The recent secondary contact between the non-native sea squirt Ciona robusta (formerly known as C. intestinalis type A) and its native congener C. intestinalis (formerly known as C. intestinalis type B), in the Western English Channel, provides an excellent case study to examine. To examine contemporary hybridization between the two species, we developed a panel of 310 ancestry informative SNPs from a population transcriptomic study. Hybridization rates were examined on 449 individuals sampled in eight sites from the sympatric range and five sites from allopatric ranges. The results clearly showed an almost complete absence of contemporary hybridization between the two species in syntopic localities, with only one-first-generation hybrid and no other genotype compatible with recent backcrosses. Despite the almost lack of contemporary hybridization, shared polymorphisms were observed in sympatric and allopatric populations of both species. Furthermore, one allopatric population from SE Pacific exhibited a higher rate of shared polymorphisms compared to all other C. robusta populations. Altogether, these results indicate that the observed level of shared polymorphism is more probably the outcome of ancient gene flow spread afterwards at a worldwide scale. They also emphasize efficient reproductive barriers preventing hybridization between introduced and native species, which suggests hybridization should not impede too much the expansion and the establishment of the non-native species in its introduction range. PMID- 27662428 TI - Toward a conceptual approach for assessing risks from chemical mixtures and other stressors to coastal ecosystem services. AB - Growth of human populations and increased human activity, particularly in coastal areas, increase pressure on coastal ecosystems and the ecosystem services (ES) they provide. As a means toward being able to assess the impact of multiple stressors on ES, in the present study we propose an 8-step conceptual approach for assessing effects of chemical mixtures and other stressors on ES in coastal areas: step A, identify the relevant problems and policy aims; step B, identify temporal and spatial boundaries; step C, identify relevant ES; step D, identify relevant stressors (e.g., chemicals); step E, translate impacts into ES units; step F, assess cumulative risk in ES units; step G, rank stressors based on their contribution to adverse effects on ES; and step H, implement regulation and management as appropriate and necessary. Two illustrative case studies (Swedish coastal waters and a coastal lagoon in Costa Rica) are provided; one focuses on chemicals that affect human food supply and the other addresses pesticide runoff and trade-offs among ES. The 2 cases are used to highlight challenges of such risk assessments, including use of standardized versus ES-relevant test species, data completeness, and trade-offs among ES. Lessons learned from the 2 case studies are discussed in relation to environmental risk assessment and management of chemical mixtures. Integr Environ Assess Manag 2017;13:376-386. (c) 2016 SETAC. PMID- 27662429 TI - Population pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin in hepatitis C virus genotype 1 infection: analysis of six phase III trials. AB - AIM: The aim of the current study was to characterize the population pharmacokinetics of a triple direct-acting antiviral (DAA) regimen (3D) (ombitasvir, paritaprevir-ritonavir and dasabuvir) and adjunctive ribavirin, and estimate covariate effects in a broad spectrum of subjects with hepatitis C virus (HCV) genotype 1 infection. METHODS: Pharmacokinetic data from six phase III studies and one phase II study in subjects receiving the currently approved doses of the 3D +/- ribavirin regimen for treating HCV genotype 1 infection for 12 weeks or 24 weeks were characterized using separate population pharmacokinetic models, built using each component of the regimen from nonlinear mixed-effects methodology in NONMEM 7.3. In the models, demographic and clinical covariates were tested. Models were assessed via goodness-of-fit plots, visual predictive checks and bootstrap evaluations. RESULTS: The population pharmacokinetic models for each component of the 3D +/- ribavirin regimen (DAAs and ritonavir, n = 2348) and ribavirin (n = 1841) adequately described their respective plasma concentration-time data. Model parameter estimates were precise and robust, and all models showed good predictive ability. Significant covariate effects associated with apparent clearance and volume of distribution included age, body weight, gender, cirrhosis, HCV subtype, opioid or antidiabetic agent use, and creatinine clearance. CONCLUSION: The population pharmacokinetics of the 3D +/- ribavirin regimen components in HCV-infected patients were characterized using phase II and III HCV clinical trial data. Although several statistically significant covariates were identified, their effects were modest and not clinically meaningful to necessitate dose adjustments for any component of the 3D regimen. PMID- 27662430 TI - Particulate matter from indoor environments of classroom induced higher cytotoxicity and leakiness in human microvascular endothelial cells in comparison with those collected from corridor. AB - We investigated the physicochemical properties (size, shape, elemental composition, and endotoxin) of size resolved particulate matter (PM) collected from the indoor and corridor environments of classrooms. A comparative hazard profiling of these PM was conducted using human microvascular endothelial cells (HMVEC). Oxidative stress-dependent cytotoxicity responses were assessed using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and high content screening (HCS), and disruption of monolayer cell integrity was assessed using fluorescence microscopy and transwell assay. Scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDX) analysis showed differences in the morphology and elemental composition of PM of different sizes and origins. While the total mass of PM collected from indoor environment was lower in comparison with those collected from the corridor, the endotoxin content was substantially higher in indoor PM (e.g., ninefold higher endotoxin level in indoor PM8.1-20 ). The ability to induce oxidative stress-mediated cytotoxicity and leakiness in cell monolayer were higher for indoor PM compared to those collected from the corridor. In conclusion, this comparative analysis suggested that indoor PM is relatively more hazardous to the endothelial system possibly because of higher endotoxin content. PMID- 27662432 TI - Identification of the monobrominated derivative of Acid Red 52 (Food Red No. 106) in pickled vegetables. AB - Two unknown dyes (purple and purplish-red) were detected by TLC in two pickled vegetable (sakura-zuke daikon) samples containing Acid Red 52 (AR) and New Coccine as food colorants. HPLC with diode-array detection and LC/MS analyses suggested that the purple dye is monobrominated AR and the purplish-red dye is its N-desethyl derivative, which would be generated mainly during sample preparation. For the identification of the purple dye, a reference compound was prepared by bromination of AR followed by isolation of the monobrominated AR, the structure of which was elucidated as 4'-brominated AR (4'BrAR) by LC/ToF-MS and (1)H-NMR spectroscopy. The purple dye was confirmed as 4'BrAR by comparison of its retention time, ultraviolet-visible spectrum and mass spectrum with those of the prepared reference compound. To our knowledge, this is the first report of the detection of 4'BrAR in foods. PMID- 27662433 TI - High-resolution mass spectrometry analysis of tetrodotoxin (TTX) and its analogues in puffer fish and shellfish. AB - Tetrodotoxin (TTX) is an emerging toxin in the European marine environment. It has various known structural analogues. It acts as a sodium channel blocker; the ability of each analogue to bind to the sodium channel varies with the particular structure of each analogue. Thus, each analogue will vary in its toxic potential. TTX analogues co-occur in food samples at variable concentrations. An LC-MS method was developed for the identification and quantitation of several analogues of TTX using an LTQ-Orbitrap XL mass spectrometer. The LTQ-Orbitrap XL mass spectrometer facilitates high mass accuracy measurement up to 100,000 full width at half maximum (FWHM). Using high resolution at 100,000 FWHM allows for the identification of TTX and its analogues in various matrices, including puffer fish and molluscan shellfish samples (Delta ppm = 0.28-3.38). The confirmation of characteristic fragment ions of TTX and its analogues was achieved by determining their elemental formulae via high mass accuracy. A quantitative method was then developed and optimised using these characteristic fragment ions. The limit of quantitation (LOQ) of the method was 0.136 ug g(-1) (S/N = 10) and the limit of detection (LOD) was 0.041 ug g(-1) (S/N = 3) spiking TTX standard into TTX-free mackerel fish extracts. The method was applied to naturally contaminated puffer fish and molluscan shellfish samples to confirm the presence of TTX and its analogues. PMID- 27662431 TI - Metabarcoding and metabolome analyses of copepod grazing reveal feeding preference and linkage to metabolite classes in dynamic microbial plankton communities. AB - In order to characterize copepod feeding in relation to microbial plankton community dynamics, we combined metabarcoding and metabolome analyses during a 22 day seawater mesocosm experiment. Nutrient amendment of mesocosms promoted the development of haptophyte (Phaeocystis pouchetii)- and diatom (Skeletonema marinoi)-dominated plankton communities in mesocosms, in which Calanus sp. copepods were incubated for 24 h in flow-through chambers to allow access to prey particles (<500 MUm). Copepods and mesocosm water sampled six times spanning the experiment were analysed using metabarcoding, while intracellular metabolite profiles of mesocosm plankton communities were generated for all experimental days. Taxon-specific metabarcoding ratios (ratio of consumed prey to available prey in the surrounding seawater) revealed diverse and dynamic copepod feeding selection, with positive selection on large diatoms, heterotrophic nanoflagellates and fungi, while smaller phytoplankton, including P. pouchetii, were passively consumed or even negatively selected according to our indicator. Our analysis of the relationship between Calanus grazing ratios and intracellular metabolite profiles indicates the importance of carbohydrates and lipids in plankton succession and copepod-prey interactions. This molecular characterization of Calanus sp. grazing therefore provides new evidence for selective feeding in mixed plankton assemblages and corroborates previous findings that copepod grazing may be coupled to the developmental and metabolic stage of the entire prey community rather than to individual prey abundances. PMID- 27662434 TI - Optical and transport properties correlation driven by amorphous/crystalline disorder in InP nanowires. AB - Indium phosphide nanowires with a single crystalline zinc-blend core and polycrystalline/amorphous shell were grown from a reliable route without the use of hazardous precursors. The nanowires are composed by a crystalline core covered by a polycrystalline shell, presenting typical lengths larger than 10 MUm and diameters of 80-90 nm. Raman spectra taken from as-grown nanowires exhibited asymmetric line shapes with broadening towards higher wave numbers which can be attributed to phonon localization effects. It was found that optical phonons in the nanowires are localized in regions with average size of 3 nm, which seems to have the same order of magnitude of grain sizes in the polycrystalline shell. Regardless of the fact that the nanowires exhibit a crystalline core, any considerable degree of disorder can lead to a localized behaviour of carriers. In consequence, the variable range hopping was observed as the main transport instead of the usual thermal excitation mechanisms. Furthermore the hopping length was ten times smaller than nanowire cross-sections, confirming that the nanostructures do behave as a 3D system. Accordingly, the V-shape observed in PL spectra clearly demonstrates a very strong influence of the potential fluctuations on the exciton optical recombination. Such fluctuations can still be observed at low temperature regime, confirming that the amorphous/polycrystalline shell of the nanowires affects the exciton recombination in every laser power regime tested. PMID- 27662435 TI - Child cyclists: A study of factors affecting their safety. AB - AIM: To study various factors that contribute to a child cyclist's risk of having, or being injured in the event of, an accident. METHODS: All children aged 8-12 years, attending four primary schools, who had access to a bicycle were invited to participate. The study consisted of: a questionnaire; a helmet and bicycle check (by professional cycle shop staff) and a practical assessment. RESULTS: Two hundred and ninety-three children participated in one or more parts of the study. Of the 214 helmets checked, 41% were deemed 'unsafe'. Forty-one percent of 205 bicycles checked were not considered roadworthy. Of the 127 children who usually ride their bicycle to school, 59% had either a bicycle that was not considered roadworthy or a helmet that was judged 'unsafe'. Of the 200 children, 91% knew the correct hand signals for a right and left turn. Eleven- and 12-year-olds were significantly better at performing the practical assessment than 8- to 10-year-olds (P < 0.0001). CONCLUSIONS: Parents cannot assume that simply providing a cycle helmet and ensuring it is worn means a child will have maximum protection in the event of an accident. Calculations that base the safety benefits of cycle helmets on observation studies are likely to be underestimates. Regular checking of the roadworthiness of a child's bicycle is advised as simple things such as underinflated tyres or worn brake pads can adversely affect handling. There is no specific age at which it can be said a young child is 'safe' to ride unaccompanied on public roads. PMID- 27662436 TI - Impact of brief communication training among hospital social workers. AB - Hospital social workers are often the fulcrum of communication between physicians, patients, and families especially when patients are facing life threatening illness. This study aims to understand the impact of a brief training for hospital social workers. The training is designed to improve communication skills and self-efficacy, as well as lessen fears of death and dying. Repeated measures tests were used to assess outcomes across three time points. Twenty-nine university-based hospital social workers participated. Results trended in the desired directions. Communication self-efficacy improved immediately following the training, and this was sustained 1 month following training completion. Although participants were relatively experienced, improvement was still demonstrated and maintained suggesting brief communication training is promising for hospital social workers across the career. PMID- 27662438 TI - Association Between Serum Fibroblast Growth Factor 21 and Mortality Among Patients With Coronary Artery Disease. AB - OBJECTIVES: Epidemiological studies have shown that serum fibroblast growth factor 21 (FGF21) levels were elevated in obesity and its related metabolic disorders. This prospective study assessed whether there was an independent association of serum FGF21 levels with all-cause and cardiovascular disease (CVD) mortality among patients with coronary artery disease (CAD). METHODS: A prospective cohort study of 1668 CAD patients was conducted. Their serum FGF21 levels were measured with ELISA kits. Cox regression models were used to estimate the association of serum FGF21 levels with the risk of mortality. RESULTS: During a median follow-up of 4.9 years, there were 194 deaths recorded and 130 of them were CVD deaths. Serum FGF21 levels positively correlated with age, body mass index, waist circumference, and adverse lipid profiles. Spline plots displayed a U-shaped association between serum FGF21 levels and all-cause as well as CVD mortality among CAD patients. Compared with serum FGF21 quartile 2, groups at quartiles 1, 3, and 4 had higher risk for all-cause and CVD mortality. Patients in the serum FGF21 quartile 4 had a 1.95-fold (95% confidence interval 1.25-3.02) risk of all-cause mortality and a 2.50-fold (95% confidence interval 1.43-4.38) risk of CVD mortality compared with those in quartile 2. CONCLUSIONS: The present study is the first to demonstrate that both higher and lower serum FGF21 levels were associated with increased risks for all-cause and CVD mortality, independent of traditional CVD risk factors. PMID- 27662437 TI - Effect of Genotype and Previous GH Treatment on Adiposity in Adults With Prader Willi Syndrome. AB - CONTEXT: Adults with Prader-Willi syndrome (PWS) have an increased proportion of sc fat mass compared with body mass index (BMI)-matched controls, but whether the genotype influences body composition and metabolic profile remains controversial. OBJECTIVE: To assess body composition and metabolic features in adults with PWS, according to genetic subtype. In addition, the effect of previous GH treatment was assessed. Main Outcomes and Measures: Body composition (Dual Energy X-ray Absorptiometry) and metabolic parameters were compared in PWS adults (mean age, 25.5 +/- 8.9 y) with deletion (n = 47) or uniparental disomy (UPD) (n = 26), taking into account GH treatment in childhood and/or adolescence. In subgroups, adipocyte size, fasting total ghrelin levels, and resting energy expenditure were measured, and hyperphagia was assessed by the Dykens Hyperphagia Questionnaire. MAIN OUTCOMES AND MEASURES: Body composition (Dual Energy X-ray Absorptiometry) and metabolic parameters were compared in PWS adults (mean age, 25.5 +/- 8.9 y) with deletion (n = 47) or uniparental disomy (UPD) (n = 26), taking into account GH treatment in childhood and/or adolescence. In subgroups, adipocyte size, fasting total ghrelin levels, and resting energy expenditure were measured, and hyperphagia was assessed by the Dykens Hyperphagia Questionnaire. RESULTS: In the whole sample, the deletion group had a higher BMI compared with UPD (40.9 +/- 11.5 vs 34.6 +/- 9.6 kg/m2, P = .02), but there was no difference between groups in percent body fat, metabolic profile, adipocyte size, resting energy expenditure, hyperphagia score, or ghrelin levels. In subjects previously treated with GH, BMI was not different between UPD and deletion groups (33.0 +/- 9.7 vs 33.5 +/- 11.1 kg/m2). In addition, previous GH treatment was associated with decreased percent body fat and adipocyte volume only in the deletion group. CONCLUSION: A deletion genotype in adults with PWS is associated with increased BMI. GH treatment in childhood and/or adolescence limits this deleterious phenotypic effect with improved adiposity markers. This study suggests relationships between the molecular phenotype of PWS and adipose tissue development as well as sensitivity to GH. PMID- 27662440 TI - The Desmopressin Test Predicts Better Than Basal Cortisol the Long-Term Surgical Outcome of Cushing's Disease. AB - CONTEXT: Cushing's disease (CD) has a significant relapse rate after successful transsphenoidal surgery (TSS). Many CD patients respond aberrantly to the desmopressin test (DT). Disappearance of this response after surgery may suggest complete removal of abnormal corticotrophs and a lower possibility of recurrence. OBJECTIVE: The utility of postoperative DT to predict long-term outcome compared to the widely used postoperative cortisol level. DESIGN: Retrospective analysis. SETTING: Tertiary hospital. PATIENTS: Seventy-three patients underwent TSS and postoperative DT; 51 had sustained remission, defined as normal dexamethasone suppression and urinary free cortisol at 6 months. After excluding 12 patients with short follow-up, negative or no preoperative DT, we analyzed 39 patients. INTERVENTION(S): Measurements of morning cortisol at 1-2 weeks and DT within 6 months after TSS. MAIN OUTCOME MEASURE(S): Recurrence or remission at latest follow-up. RESULTS: Mean follow-up was 63 +/- 50 months. Recurrence occurred in seven patients. In logistic regression analysis, postoperative cortisol levels were not associated with remission. Apart from the percentage increment of cortisol, all other DT criteria (peak cortisol, peak ACTH, absolute cortisol increment [DeltaCort], absolute ACTH change, and percentage absolute ACTH change) were significant predictors of outcome. In receiver operating characteristic analysis, the DeltaCort had the best diagnostic performance. DeltaCort <7.4 MUg/dL had a sensitivity of 97% to detect remission. Comparison of Kaplan-Meier curves showed that DeltaCort <7.4 MUg/dL was associated with remission, whereas DeltaCort >=7.4 MUg/dL had a hazard ratio of recurrence of 24.7 (95% confidence interval, 10.6-448.5) at 60 months (median). CONCLUSION: Loss of desmopressin response indicates favorable prognosis and, if used in addition to basal cortisol levels, improves the accuracy of the postoperative assessment of CD. PMID- 27662439 TI - Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss. AB - CONTEXT: Some men who use finasteride for hair loss report persistent sexual and other symptoms after discontinuing finasteride therapy. OBJECTIVE: To determine whether these persistent symptoms after discontinuation of finasteride use are due to androgen deficiency, decreased peripheral androgen action, or persistent inhibition of steroid 5alpha-reductase (SRD5A) enzymes. PARTICIPANTS: Finasteride users, who reported persistent sexual symptoms after discontinuing finasteride (group 1); age-matched finasteride users who did not report sexual symptoms (group 2); and healthy men who had never used finasteride (group 3). OUTCOMES: Sexual function, mood, affect, cognition, hormone levels, body composition, functional magnetic resonance imaging (fMRI) response to sexually and affectively valenced stimuli, nucleotide sequences of androgen receptor (AR), SRD5A1, and SRD5A2; expression levels of androgen-dependent genes in skin. SETTING: Academic medical center. RESULTS: Symptomatic finasteride users were similar in body composition, strength, and nucleotide sequences of AR, SRD5A1, and SRD5A2 genes to asymptomatic finasteride users and nonusers. Symptomatic finasteride users had impaired sexual function, higher depression scores, a more negative affectivity balance, and more cognitive complaints than men in groups 2 and 3 but had normal objectively assessed cognitive function. Testosterone, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol-glucuronide, testosterone to dihydrotestosterone and androsterone glucuronide to etiocholanolone glucuronide ratios, and markers of peripheral androgen action and expression levels of AR dependent genes in skin did not differ among groups. fMRI blood oxygen level dependent responses to erotic and nonerotic stimuli revealed abnormal function in brain circuitry linked to sexual arousal and major depression. CONCLUSIONS: We found no evidence of androgen deficiency, decreased peripheral androgen action, or persistent peripheral inhibition of SRD5A in men with persistent sexual symptoms after finasteride use. Symptomatic finasteride users revealed depressed mood and fMRI findings consistent with those observed in depression. PMID- 27662441 TI - Bone Metastases and Skeletal-Related Events in Medullary Thyroid Carcinoma. AB - CONTEXT: Bone metastases (BM) can lead to devastating skeletal-related events (SREs) in cancer patients. Data regarding medullary thyroid carcinoma (MTC) with BM are lacking. OBJECTIVE: We evaluated the natural history of BM and SREs in MTC patients identified by a cancer center tumor registry. SETTING: The study was conducted at a tertiary cancer center. PATIENTS AND MAIN OUTCOME MEASURES: We retrospectively reviewed the charts of MTC patients with BM who received care from 1991 to 2014 to characterize BM and SREs. RESULTS: Of 1008 MTC patients treated, 188 were confirmed to have BM (19%), of whom 89% (168 of 188) had nonosseous distant metastases. Median time from MTC to BM diagnosis was 30.9 months (range 0-533 mo); 25% (45 of 180) had BM identified within 3 months of MTC diagnosis. Median follow-up after detecting BM was 1.6 years (range 0-23.2 y). Most patients (77%) had six or more BM lesions, most often affecting the spine (92%) and pelvis (69%). Many patients (90 of 188, 48%) experienced one or more SREs, most commonly radiotherapy (67 of 90, 74%) followed by pathological fracture (21 of 90, 23%). Only three patients had spinal cord compression. Patients with more than 10 BM lesions were more likely to experience SREs (odds ratio 2.4; P = .007), with no difference in 5-year mortality after MTC diagnosis between patients with (31%) and without SREs (23%) (P = .11). CONCLUSIONS: In this large retrospective series, BM in MTC was multifocal, primarily involving the spine and pelvis, supporting screening these regions for metastases in at risk patients. SREs were common but spinal cord compression was rare. Antiresorptive therapies in this population should be investigated further with prospective trials. PMID- 27662442 TI - Perceptions of Provider Communication Among Vulnerable Patients With Diabetes: Influences of Medical Mistrust and Health Literacy. AB - Patient-provider communication is modifiable and is linked to diabetes outcomes. The association of communication quality with medical mistrust is unknown. We examined these factors within the context of a low-literacy/numeracy-focused intervention to improve diabetes care, using baseline data from diverse patients enrolled in a randomized trial of a health communication intervention. Demographics, measures of health communication (Communication Assessment Tool [CAT], Interpersonal Processes of Care survey [IPC-18]), health literacy (Short Test of Functional Health Literacy in Adults), depression, medical mistrust, and glycemic control were ascertained. Adjusted proportional odds models were used to test the association of mistrust with patient-reported communication quality. The interaction effect of health literacy on mistrust and communication quality was also assessed. A total of 410 patients were analyzed. High levels of mistrust were observed. In multivariable modeling, patients with higher mistrust had lower adjusted odds of reporting a higher CAT score (adjusted odds ratio [AOR] = 0.67, 95% confidence interval [CI] [0.52, 0.86], p = .003) and higher scores on the Communication (AOR = 0.69, 95% CI [0.55, 0.88], p = .008), Decided Together (AOR = 0.74, 95% CI [0.59, 0.93], p = .02), and Interpersonal Style (AOR = 0.69, 95% CI [0.53, 0.90], p = .015) subscales of the IPC-18. We observed evidence of an interaction effect of health literacy for the association between mistrust and the Decided Together subscale of the IPC-18 such that patients with higher mistrust and lower literacy perceived worse communication relative to mistrustful patients with higher literacy. In conclusion, medical mistrust was associated with poorer communication with providers in this public health setting. Patients' health literacy level may vary the effect of mistrust on interactional aspects of communication. Providers should consider the impact of mistrust on communication with vulnerable diabetes populations and focus efforts on mitigating its influence. PMID- 27662444 TI - Corrigendum. PMID- 27662445 TI - A retrospective study to reveal factors associated with postoperative shoulder imbalance in patients with adolescent idiopathic scoliosis with double thoracic curve. AB - OBJECTIVE Postoperative shoulder imbalance (PSI) is a critical consideration after corrective surgery for a double thoracic curve (Lenke Type 2); however, the radiographic factors related to PSI remain unclear. The purpose of this study was to identify the radiographic factors related to PSI after corrective surgery for adolescent idiopathic scoliosis (AIS) in patients with a double thoracic curve. METHODS This study included 80 patients with Lenke Type 2 AIS who underwent corrective surgery. Patients were grouped according to the presence [PSI(+)] or absence [PSI(-)] of shoulder imbalance at the final follow-up examination (differences of 20, 15, and 10 mm were used). Various radiographic parameters, including the Cobb angle of the proximal and middle thoracic curves (PTC and MTC), radiographic shoulder height (RSH), clavicle angle, T-1 tilt, trunk shift, and proximal and distal wedge angles (PWA and DWA), were assessed before and after surgery and compared between groups. RESULTS Overall, postoperative RSH decreased with time in the PSI(-) group but not in the PSI(+) group. Statistical analyses revealed that the preoperative Risser grade (p = 0.048), postoperative PWA (p = 0.028), and postoperative PTC/MTC ratio (p = 0.011) correlated with PSI. Presence of the adding-on phenomenon was also correlated with PSI, although this result was not statistically significant (p = 0.089). CONCLUSIONS Postoperative shoulder imbalance is common after corrective surgery for Lenke Type 2 AIS and correlates with a higher Risser grade, a larger postoperative PWA, and a higher postoperative PTC/MTC ratio. Presence of the distal adding-on phenomenon is associated with an increased PSI trend, although this result was not statistically significant. However, preoperative factors other than the Risser grade that affect the development of PSI were not identified by the study. Additional studies are required to reveal the risk factors for the development of PSI. PMID- 27662443 TI - Histone deacetylase 3 suppresses Erk phosphorylation and matrix metalloproteinase (Mmp)-13 activity in chondrocytes. AB - Histone deacetylase (Hdac3) inhibitors are emerging therapies for many diseases including cancers and neurological disorders; however, these drugs are teratogens to the developing skeleton. Hdac3 is essential for proper endochondral ossification as its deletion in chondrocytes increases cytokine signaling and the expression of matrix remodeling enzymes. Here we explored the mechanism by which Hdac3 controls matrix metalloproteinase (Mmp)-13 expression in chondrocytes. In Hdac3-depleted chondrocytes, extracellular signal-regulated kinase (Erk)1/2 as well as its downstream substrate, Runx2, were hyperphosphorylated as a result of decreased expression and activity of the Erk1/2 specific phosphatase, Dusp6. Erk1/2 kinase inhibitors and Dusp6 adenoviruses reduced Mmp13 expression and partially rescued matrix production in Hdac3-deficient chondrocytes. Postnatal chondrocyte-specific deletion of Hdac3 with an inducible Col2a1-Cre caused premature production of pErk1/2 and Mmp13 in the growth plate. Thus, Hdac3 controls the temporal and spatial expression of tissue-remodeling genes in chondrocytes to ensure proper endochondral ossification during development. PMID- 27662446 TI - Thoracic osteomyelitis and epidural abscess formation due to cat scratch disease: case report. AB - Osteomyelitis of the spine with associated spinal epidural abscess represents an uncommon entity in the pediatric population, requiring prompt evaluation and diagnosis to prevent neurological compromise. Cat scratch disease, caused by the pathogen Bartonella henselae, encompasses a wide spectrum of clinical presentations; however, an association with osteomyelitis and epidural abscess has been reported in only 4 other instances in the literature. The authors report a rare case of multifocal thoracic osteomyelitis with an epidural abscess in a patient with a biopsy-proven pathogen of cat scratch disease. A 5-year-old girl, who initially presented with vague constitutional symptoms, was diagnosed with cat scratch disease following biopsy of an inguinal lymph node. Despite appropriate antibiotics, she presented several weeks later with recurrent symptoms and back pain. Magnetic resonance imaging revealed 2 foci of osteomyelitis at T-8 and T-11 with an associated anterior epidural abscess from T 9 to T-12. Percutaneous image-guided vertebral biopsy revealed B. henselae by polymerase chain reaction analysis, and she was treated conservatively with doxycycline and rifampin with favorable clinical outcome. PMID- 27662448 TI - Synthesis, characterization, and biological activity of cross-linked chitosan biguanidine loaded with silver nanoparticles. AB - Chitosan biguanidine hydrochloride (ChG) and glutaraldehyde cross-linked chitosan biguanidine (CChG) were synthesized and characterized by Fourier transform infrared spectroscopy, 1H NMR and 13C NMR, X-ray diffraction, scanning electron microscopy (SEM) and thermal analyses (TGA and DTA). The results showed that ChG and CChG had a more amorphous structure than that of chitosan, and their thermal stability were slightly lower than that of chitosan. Colloidal silver nanoparticles (AgNPs) were prepared using borohydride reduction method and then investigated as fillers in partially cross-linked chitosan biguanidine. The obtained nanoparticles were uniform and spherical with average size of 9.6 +/- 0.5 nm. The prepared CChG/AgNPs composites were characterized for their morphology, thermal properties, cytotoxicity and antimicrobial activity. The SEM images showed that the AgNPs are well imbedded in the CChG matrix. The thermal stability of CChG was improved with incorporation of AgNPs. The CChG and CChG/AgNPs showed less cytotoxicity to breast cancer cells (MCF-7). Compared with chitosan and CChG, the ChG and CChG/AgNPs showed better antimicrobial activity against Streptococcus pneumoniae and Bacillus subtilis as Gram-positive bacteria, Escherichia coli as Gram-negative bacteria and Aspergillus fumigatus, Geotricum candidum and Syncephalastrum recemosum as fungi. PMID- 27662447 TI - Planning a Stigmatized Nonvisible Illness Disclosure: Applying the Disclosure Decision-Making Model. AB - This study applied the disclosure decision-making model (DD-MM) to explore how individuals plan to disclose nonvisible illness (Study 1), compared to planning to disclose personal information (Study 2). Study 1 showed that perceived stigma from the illness negatively predicted disclosure efficacy; closeness predicted anticipated response (i.e., provision of support) although it did not influence disclosure efficacy; disclosure efficacy led to reduced planning, with planning leading to scheduling. Study 2 demonstrated that when information was considered to be intimate, it negatively influenced disclosure efficacy. Unlike the model with stigma (Study 1), closeness positively predicted both anticipated response and disclosure efficacy. The rest of the hypothesized relationships showed a similar pattern to Study 1: disclosure efficacy reduced planning, which then positively influenced scheduling. Implications of understanding stages of planning for stigmatized information are discussed. PMID- 27662449 TI - tDCS Effects on Verbal Fluency: A Response to Vannorsdall et al (2016). AB - In a prior study (Cattaneo et al, 2011. Neuroscience. 183:64-70), we demonstrated that anodal transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus enhanced verbal fluency in healthy young adults. Although our data are in line with the results of other published studies, another research group recently failed to report anodal tDCS effects on verbal fluency using a paradigm similar to ours (Vannorsdall et al, 2016. Cogn Behav Neurol. 29:11-17). Here we discuss aspects of study design and interpretation of results that should be considered in replications, focusing particularly on homogeneity of procedures. Notwithstanding the possibility that our study may indeed not be replicable, we hypothesize that Vannorsdall et al found an interesting modifier of the tDCS effects on verbal production by introducing a critical methodologic difference from our original study. We demonstrate this difference by presenting the results of an additional experiment. We believe that the sharing of data between research groups and constructive debate on possible differences in results should be encouraged because they help define the boundaries of applicability of an experimental paradigm. This is even more important for research findings that may have clinical implications, as is the case here. PMID- 27662451 TI - Basal Ganglia Calcification in Psychiatric Inpatients: A Case-Control Study. AB - BACKGROUND AND OBJECTIVE: Several case reports have noted basal ganglia calcification (BGC) as an incidental radiologic finding in patients presenting with psychiatric manifestations. In this study, we examined the clinical correlates of mental disorders in two groups of psychiatric patients, one with BGC and one with normal radiologic studies. METHODS: In a retrospective cross sectional case-control study of patients admitted to the psychiatric ward in Al Ain Hospital between January 2011 and December 2013, we compared all 15 patients diagnosed with BGC and 30 control patients who had normal radiologic findings. RESULTS: The BGC group's psychiatric symptoms began when they were aged in their 30s and 40s, later than the controls' 20s and 30s (P=0.001). More of the BGC group than the controls had cognitive symptoms (60% versus 6.7%, P=0.001). The BGC group was more likely to have chronic medical comorbidities (66.7% versus 20%, P=0.003). The BGC group's mean serum calcium was lower than the controls' (P=0.003) and the C-reactive protein was higher (P=0.049). We did not find significant differences between the groups in psychiatric diagnoses; five of the 15 patients with BGC had mood disorders and four of the 15 had psychotic disorders. CONCLUSIONS: Patients with BGC tend to develop psychiatric symptoms later in life than other psychiatric patients, and have higher rates of medical comorbidities. Many patients with BGC have cognitive symptoms, which can be concurrent with a mood or psychotic disorder. PMID- 27662452 TI - Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease. AB - OBJECTIVE: We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. BACKGROUND: Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. METHODS: We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). RESULTS: The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r= 0.381, P=0.003). CONCLUSIONS: Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined. PMID- 27662450 TI - Effects of Testosterone Therapy on Cognitive Function in Aging: A Systematic Review. AB - Endogenous testosterone in the aging man has been scrutinized extensively in regard to its effects on performance in many cognitive domains, especially verbal fluency, visuospatial and visuoperceptual abilities, memory, and executive function. Studies of testosterone supplementation have sought to identify potential cognitive improvements in men with and without baseline cognitive impairment, and have had a wide range of results. The variability in outcomes is likely related, in part, to the lack of consensus on methods for testosterone measurement and supplementation and, in part, to the disparate measures of cognitive function used in randomized controlled studies. Despite the limitations imposed by such inconsistent methods, promising associations have been found between cognition and testosterone supplementation in both eugonadal men and men with low testosterone levels, with and without baseline cognitive dysfunction. This systematic review highlights the cognitive measures used in and the outcomes of existing studies of testosterone and cognition in aging men. The review suggests that larger studies and a more standardized approach to assessment will be needed before we can fully understand and realize sustained benefits from testosterone supplementation in the elderly male population, particularly given the substantial increase in testosterone supplementation in clinical practice. PMID- 27662453 TI - A Case of Reduplicative Paramnesia for Home. AB - We present the case of a high-functioning 88-year-old woman who suddenly developed the persistent and disturbing belief that her home of 40 years was not genuine, but rather an accurate replica. Her episode was probably caused by a small stroke that left her with this single extremely specific deficit. We describe the patient in detail and link to a video interview of her 3 months after the onset of the delusion, eloquently describing her experience. We summarize some of the many reports and discussions of our patient's delusion, reduplicative paramnesia, as well as other delusional misidentification syndromes. PMID- 27662455 TI - Erratum to "How Information Visualization Novices Construct Visualizations". PMID- 27662454 TI - Left Dorsomedial Thalamic Damage Impairs Verbal Recall More Than Recognition: A Case Report. AB - Damage to the dorsomedial thalamus usually leads to impaired episodic memory, attention, and executive function, but the role of the dorsomedial thalamus in memory processing is still not fully understood. Clinical evidence is inconclusive about whether dorsomedial thalamic damage impairs recall or whether it impairs recognition. I report a unique patient who suffered a cardioembolic stroke in the paramedian artery territory, caused by a patent foramen ovale. He was left with a chronic ischemic lesion centered in the parvocellular and, to a lesser extent, the magnocellular portions of the left dorsomedial thalamic nucleus, and marginally involving the midline and intralaminar nuclei. A year after the stroke, the patient's neuropsychological assessment showed a selective verbal memory deficit with greater loss of recall than recognition. His memory was normal when he was given semantically encoded material. His test results showed that damage to the left dorsomedial thalamic nucleus might affect both his recall and recognition because of the involvement of the parvocellular and magnocellular portions, respectively. The results also suggest that the left dorsomedial thalamus is involved in the encoding of verbal material. This case report highlights the role that the left dorsomedial thalamus plays in processing memory specific to verbal material. The findings point to the differential contribution of the dorsomedial parvocellular nucleus to recall, and support the theory that prefrontal strategic memory is enabled by adequate encoding of information through thalamocortical connectivity with the dorsolateral prefrontal cortex. PMID- 27662456 TI - Effects of Global and Local Anharmonicities on the Thermodynamic Properties of Sulfuric Acid Monohydrate. AB - We use state-of-the-art electronic structure calculation methods and large basis sets to obtain reliable values for the thermodynamic properties of sulfuric acid monohydrate and study the effects of vibrational anharmonicity on these properties. We distinguish between two forms of vibrational anharmonicity: local anharmonicity, which refers to the anharmonicity of the vibrational modes of a given cluster conformer, and global anharmonicity, which originates from accounting for the presence of different conformers in the first place. In our most accurate approach, we solve the nuclear Schrodinger equation variationally for the intermolecular large-amplitude motions, thus quantum-mechanically accounting for the presence of higher-energy conformers for both reactants and products, while using the standard vibrational perturbational approach for the other vibrational modes. This results in a value of -11.0 kJ/mol for the reaction Gibbs free energy at 298.15 K. When standard vibrational perturbational approaches are employed, the effects of local anharmonicity depend heavily on the choice of the electronic structure calculation basis set. In fact, better results can often be achieved by combining a simple harmonic treatment for the vibrational partition function with a statistical mechanical accounting of global anharmonicity. Thus, we recommend that future studies that intend to include anharmonicity start by accounting for the presence of higher-energy conformers and only then consider whether local anharmonicity calculations are feasible and necessary. PMID- 27662457 TI - Status Epilepticus Associated With Risperidone and Methylphenidate in an Adolescent With Epilepsy: A Case Report. PMID- 27662458 TI - Prevalence of Vitamin D Deficiency in Adult Outpatients With Bipolar Disorder or Schizophrenia. AB - OBJECTIVE: Several studies show an association between schizophrenia and low levels of vitamin D. To date, there are only few studies about the prevalence of vitamin D deficiency in patients with bipolar disorder. We hypothesized that vitamin D deficiency is less common among patients with bipolar disorder than among patients with schizophrenia or schizoaffective disorder. A second hypothesis is that vitamin D deficiency is more prevalent among patients with schizophrenia, schizoaffective disorder, or bipolar disorders than among the general Dutch population.Most studies have been conducted with hospitalized patients; in this study, we only included outpatients. METHODS: All outpatients of a center for bipolar disorders and all outpatients of 3 flexible assertive community treatment teams were asked to participate in this cross-sectional study. RESULTS: We included 118 patients with bipolar disorder and 202 patients with schizophrenia or schizoaffective disorder. Vitamin D levels were deficient in 30.3% (95% confidence interval, 25.5-35.6) of the cases. The type of psychiatric disorder was not a predictor of vitamin D deficiency. The absolute difference in risk of deficiency between the study population and the Dutch Caucasian population was 23.8% (95% confidence interval, 18.3%-29.3%). CONCLUSIONS: In this study, vitamin D deficiency was 4.7 times more common among outpatients with bipolar disorder, schizophrenia, or schizoaffective disorder than among the Dutch general population.Given the high prevalence of vitamin D deficiency, we believe that outpatients with bipolar disorder, schizophrenia, or schizoaffective disorder should be considered at risk of having low levels of vitamin D. Annual measurement of vitamin D levels in psychiatric outpatients with these disorders seems to be justified to maintain bone health, muscle strength, and to prevent osteoporosis. PMID- 27662459 TI - Prescribing Practice in Inpatients Versus Outpatients With Schizophrenia Initiating Treatment With Second-Generation Antipsychotics: A Naturalistic Follow Up Study. AB - OBJECTIVE: The primary objective of this study was to investigate whether the choice and dosage of antipsychotic medication differ between patients with schizophrenia starting treatment in an inpatient or outpatient unit. In addition, we investigated whether the reason for the introduction of new antipsychotic medication had an impact on the treatment setting and whether the use of benzodiazepines differed between inpatients and outpatients. METHOD: From October 1997 to September 2010, patients with a schizophrenia spectrum disorder according to the International Classification of Diseases, Tenth Revision aged between 18 and 65 years were allocated to a naturalistic drug-monitoring program when starting treatment with a second-generation antipsychotic drug. Psychopathological symptoms were rated at baseline and after 1, 2, 4, and 8 weeks of treatment using the Positive and Negative Syndrome Scale. Inpatients and outpatients were compared with regard to the use of antipsychotics and benzodiazepines. To compare different drugs, chlorpromazine and diazepam equivalents were calculated. RESULTS: Lack of efficacy and side effects were the main reasons for initiating new antipsychotic medication. Combined evaluation of all antipsychotic compounds by meta-analysis resulted in a significant effect of the treatment setting, with inpatients receiving higher doses than outpatients. In addition, inpatients were prescribed benzodiazepines more often and in higher doses than outpatients. CONCLUSIONS: Both antipsychotics and benzodiazepines were prescribed at higher doses in an inpatient setting. Moreover, benzodiazepines were prescribed more frequently to inpatients. Accordingly, the treatment setting needs to be taken into consideration in treatment recommendations for schizophrenia spectrum disorders. PMID- 27662460 TI - Adhesion of Blood Plasma Proteins and Platelet-rich Plasma on l-Valine-Based Poly(ester urea). AB - The competitive absorption of blood plasma components including fibrinogen (FG), bovine serum albumin (BSA), and platelet-rich plasma (PRP) on l-valine-based poly(ester urea) (PEU) surfaces were investigated. Using four different PEU polymers, possessing compositionally dependent trends in thermal, mechanical, and critical surface tension measurements, water uptake studies were carried out to determine in vitro behavior of the materials. Quartz crystal microbalance (QCM) measurements were used to quantify the adsorption characteristics of PRP onto PEU thin films by coating the surfaces initially with FG or BSA. Pretreatment of the PEU surfaces with FG inhibited the adsorption of PRP and BSA decreased the absorption 4-fold. In vitro studies demonstrated that cells cultured on l-valine based PEU thin films allowed attachment and spreading of rat aortic cells. These measurements will be critical toward efforts to use this new class of materials in blood-contacting biomaterials applications. PMID- 27662461 TI - Controllable Broadband Optical Transparency and Wettability Switching of Temperature-Activated Solid/Liquid-Infused Nanofibrous Membranes. AB - Inspired by biointerfaces, such as the surfaces of lotus leaves and pitcher plants, researchers have developed innovative strategies for controlling surface wettability and transparency. In particular, great success has been achieved in obtaining low adhesion and high transmittance via the introduction of a liquid layer to form liquid-infused surfaces. Furthermore, smart surfaces that can change their surface properties according to external stimuli have recently attracted substantial interest. As some of the best-performing smart surface materials, slippery liquid-infused porous surfaces (SLIPSs), which are super repellent, demonstrate the successful achievement of switchable adhesion and tunable transparency that can be controlled by a graded mechanical stimulus. However, despite considerable efforts, producing temperature-responsive, super repellent surfaces at ambient temperature and pressure remains difficult because of the use of nonreactive lubricant oil as a building block in previously investigated repellent surfaces. Therefore, the present study focused on developing multifunctional materials that dynamically adapt to temperature changes. Here, we demonstrate temperature-activated solidifiable/liquid paraffin infused porous surfaces (TA-SLIPSs) whose transparency and control of water droplet movement at room temperature can be simultaneously controlled. The solidification of the paraffin changes the surface morphology and the size of the light-transmission inhibitor in the lubricant layer; as a result, the control over the droplet movement and the light transmittance at different temperatures is dependent on the solidifiable/liquid paraffin mixing ratio. Further study of such temperature-responsive, multifunctional systems would be valuable for antifouling applications and the development of surfaces with tunable optical transparency for innovative medical applications, intelligent windows, and other devices. PMID- 27662462 TI - Outcomes of Adding Patient and Family Engagement Education to Fall Prevention Bundled Interventions. AB - Nurses strive to reduce risk and ensure patient safety from falls in health care systems. Patients and their families are able to take a more active role in reducing falls. The focus of this article is on the use of bundled fall prevention interventions highlighted by a patient/family engagement educational video. The implementation of this quality improvement intervention across 2 different patient populations was successful in achieving unit benchmarks. PMID- 27662464 TI - How Do Modern Pesticide Treatments Influence the Mobility of Old Incurred DDT Contaminations in Agricultural Soils? AB - Even more than 50 years after the ban of DDT in Germany, farmers are still affected by its persistence in contaminated soils. Depending on the crop cultivated on such soils, this often leads to low-level residues of DDT and its metabolites DDE and DDD ("DDX"), which are perceived as a risk by the food value chain. Pesticide formulations used in modern agriculture commonly contain high levels of surfactants, but so far no open-field studies have evaluated the effects of these treatments on the mobility of lipophilic contaminants, such as DDX. In this field trial, a 1.03 ha section was cultivated with Cucurbita maxima under realistic conditions to monitor the mobility of DDX in low-level contaminated agricultural soils in dependence of common pesticide applications. A typical organic treatment was compared to a conventional protocol. Soil samples were taken before and after each application. Samples from the organic section featured significantly higher extractable DDX contents in soil and water compared to the conventional section. The results show that modern pesticide treatments can have an unforeseen, yet significant influence on the mobilization and, subsequently, on the plant bioavailability of incurred DDX residues depending on the formulation composition. PMID- 27662463 TI - Human Brucellosis in Febrile Patients Seeking Treatment at Remote Hospitals, Northeastern Kenya, 2014-2015. AB - During 2014-2015, patients in northeastern Kenya were assessed for brucellosis and characteristics that might help clinicians identify brucellosis. Among 146 confirmed brucellosis patients, 29 (20%) had negative serologic tests. No clinical feature was a good indicator of infection, which was associated with animal contact and drinking raw milk. PMID- 27662465 TI - Cochlear Hypoplasia Type Four With Anteriorly Displaced Facial Nerve Canal. PMID- 27662466 TI - Developing new automated alternation flicker using optic disc photography for the detection of glaucoma progression. AB - PurposeTo evaluate a progression-detecting algorithm for a new automated matched alternation flicker (AMAF) in glaucoma patients.MethodsOpen-angle glaucoma patients with a baseline mean deviation of visual field (VF) test>-6 dB were included in this longitudinal and retrospective study. Functional progression was detected by two VF progression criteria and structural progression by both AMAF and conventional comparison methods using optic disc and retinal nerve fiber layer (RNFL) photography. Progression-detecting performances of AMAF and the conventional method were evaluated by an agreement between functional and structural progression criteria. RNFL thickness changes measured by optical coherence tomography (OCT) were compared between progressing and stable eyes determined by each method.ResultsAmong 103 eyes, 47 (45.6%), 21 (20.4%), and 32 (31.1%) eyes were evaluated as glaucoma progression using AMAF, the conventional method, and guided progression analysis (GPA) of the VF test, respectively. The AMAF showed better agreement than the conventional method, using GPA of the VF test (kappa=0.337; P<0.001 and kappa=0.124; P=0.191, respectively). The rates of RNFL thickness decay using OCT were significantly different between the progressing and stable eyes when progression was determined by AMAF (-3.49+/-2.86 MUm per year vs -1.83+/-3.22 MUm per year; P=0.007) but not by the conventional method (-3.24+/-2.42 MUm per year vs -2.42+/-3.33 MUm per year; P=0.290).ConclusionsThe AMAF was better than the conventional comparison method in discriminating structural changes during glaucoma progression, and showed a moderate agreement with functional progression criteria. PMID- 27662468 TI - Aggregation, Adsorption, and Morphological Transformation of Graphene Oxide in Aqueous Solutions Containing Different Metal Cations. AB - The colloidal behavior of graphene oxide (GO) has been extensively studied in the presence of common environmental cations, but the aggregation, adsorption, and morphological transformation of GO under heavy metal ions have not been investigated. We observed that heavy metal cations (Cr3+, Pb2+, Cu2+, Cd2+, Ag+) destabilized GO suspension more aggressively than common cations (Ca2+, Mg2+, Na+, K+). In addition to electric double-layer (EDL) suppression, heavy metal cations can easily cross the EDL, bind to GO surface, and then change the surface potential, which is a more efficient pathway for GO aggregation. According to aggregation kinetics, the destabilizing ability of cations follows the order of Cr3+ ? Pb2+ > Cu2+ > Cd2+ > Ca2+ > Mg2+ ? Ag+ > K+ > Na+. The destabilizing capability of metal cations is consistent with their adsorption affinity with GO, which is determined by their electronegativity and hydration shell thickness. GO nanosheets can be transformed to 1D tube-like carbon material, 2D multiple overlapped GO plane, and 3D sphere-like particles during aggregation, thereby combined to form a sphere-like aggregated GO, which is for the first time observed by TEM and AFM images. Therefore, the aggregation of GO 2D nanosheets follows the Schulze-Hardy rule, which is usually used for spherical particles. An integrative process of adsorption-transformation-aggregation is proposed to better understand the nanomaterial (e.g., GO) colloidal behavior, environmental risk, self-assembly process, and application as a novel adsorbent. PMID- 27662467 TI - Neocentromeres Provide Chromosome Segregation Accuracy and Centromere Clustering to Multiple Loci along a Candida albicans Chromosome. AB - Assembly of kinetochore complexes, involving greater than one hundred proteins, is essential for chromosome segregation and genome stability. Neocentromeres, or new centromeres, occur when kinetochores assemble de novo, at DNA loci not previously associated with kinetochore proteins, and they restore chromosome segregation to chromosomes lacking a functional centromere. Neocentromeres have been observed in a number of diseases and may play an evolutionary role in adaptation or speciation. However, the consequences of neocentromere formation on chromosome missegregation rates, gene expression, and three-dimensional (3D) nuclear structure are not well understood. Here, we used Candida albicans, an organism with small, epigenetically-inherited centromeres, as a model system to study the functions of twenty different neocentromere loci along a single chromosome, chromosome 5. Comparison of neocentromere properties relative to native centromere functions revealed that all twenty neocentromeres mediated chromosome segregation, albeit to different degrees. Some neocentromeres also caused reduced levels of transcription from genes found within the neocentromere region. Furthermore, like native centromeres, neocentromeres clustered in 3D with active/functional centromeres, indicating that formation of a new centromere mediates the reorganization of 3D nuclear architecture. This demonstrates that centromere clustering depends on epigenetically defined function and not on the primary DNA sequence, and that neocentromere function is independent of its distance from the native centromere position. Together, the results show that a neocentromere can form at many loci along a chromosome and can support the assembly of a functional kinetochore that exhibits native centromere functions including chromosome segregation accuracy and centromere clustering within the nucleus. PMID- 27662470 TI - Comorbidities of chronic facial pain and obstructive sleep apnea. AB - PURPOSE OF REVIEW: This article explains the high comorbidity of craniofacial pain (chronic face pain, temporomandibular disorders, and primary headaches) with obstructive sleep breathing disorders and obstructive sleep apnea (OSA). It is recommended that physicians treating OSA should be aware of the concurrent chronic pain that affects the quality of sleep, and also dentists treating chronic pain be aware of a sleep breathing origin so that proper reciprocal referrals be made for optimal patient treatment outcome. RECENT FINDINGS: These comorbid relationships are not limited to adults. The most recent literature demonstrates that children diagnosed with primary headaches are highly comorbid with OSA and frequently have chronic facial pain complaints. SUMMARY: It is recommended that patients who seek care for the symptoms of sleep-related breathing disorders (OSA), or patients seeking care for chronic head and face pain be screened with intake forms that include questions of both to insure optimal treatment outcomes for either chief complaint. PMID- 27662469 TI - An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma. AB - BACKGROUND: With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses. METHODS: In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100 fold or the cffDNA fraction is less than 10%. RESULTS: Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome. PMID- 27662471 TI - Genetic Spectrum of Idiopathic Restrictive Cardiomyopathy Uncovered by Next Generation Sequencing. AB - BACKGROUND: Cardiomyopathies represent a rare group of disorders often of genetic origin. While approximately 50% of genetic causes are known for other types of cardiomyopathies, the genetic spectrum of restrictive cardiomyopathy (RCM) is largely unknown. The aim of the present study was to identify the genetic background of idiopathic RCM and to compile the obtained genetic variants to the novel signalling pathways using in silico protein network analysis. PATIENTS AND METHODS: We used Illumina MiSeq setup to screen for 108 cardiomyopathy and arrhythmia-associated genes in 24 patients with idiopathic RCM. Pathogenicity of genetic variants was classified according to American College of Medical Genetics and Genomics classification. RESULTS: Pathogenic and likely-pathogenic variants were detected in 13 of 24 patients resulting in an overall genotype-positive rate of 54%. Half of the genotype-positive patients carried a combination of pathogenic, likely-pathogenic variants and variants of unknown significance. The most frequent combination included mutations in sarcomeric and cytoskeletal genes (38%). A bioinformatics approach underlined the mechanotransducing protein networks important for RCM pathogenesis. CONCLUSIONS: Multiple gene mutations were detected in half of the RCM cases, with a combination of sarcomeric and cytoskeletal gene mutations being the most common. Mutations of genes encoding sarcomeric, cytoskeletal, and Z-line-associated proteins appear to have a predominant role in the development of RCM. PMID- 27662472 TI - Mutation Analysis of 16 Mucolipidosis II and III Alpha/Beta Chinese Children Revealed Genotype-Phenotype Correlations. AB - Mucolipidosis II and III alpha/beta are autosomal recessive diseases caused by mutations in the GNPTAB gene which encodes the alpha and beta subunits of the N acetylglucosamine-1-phosphotransferase. Clinically, mucolipidosis II (MLII) is characterized by severe developmental delay, coarse facial features, skeletal deformities, and other systemic involvement. In contrast, MLIII alpha/beta is a much milder disorder, the symptoms of which include progressive joint stiffness, short stature, and scoliosis. To study the relationship between the genotypes and phenotypes of the MLII and MLIII alpha/beta patients, we analyzed the GNPTAB gene in 16 Chinese MLII and MLIII alpha/beta patients. We collected and analyzed the patients' available clinical data and all showed clinical features typical of MLII or MLIII alpha/beta. Moreover, the activity of several lysosomal enzymes was measured in the plasma and finally the GNPTAB gene was sequenced. We detected 30 mutant alleles out of 32 alleles in our patients. These include 10 new mutations (c.99delC, c.118-1G>A, c.523_524delAAinsG, c.1212C>G, c.2213C>A, c.2345C>T, c.2356C>T, c.2455G>T, c.2821dupA, and c.3136-2A>G) and 5 previously reported mutations (c.1071G>A, c.1090C>T, c.2715+1G>A, c.2550_2554delGAAA, and c.3613C>T). The most frequent mutation was the splicing mutation c.2715+1G>A, which accounted for 28% of the mutations. The majority of the mutations reported in the Chinese patients (57%) were located on exon 13 or in its intronic flanking regions. PMID- 27662473 TI - Antidiabetic and antihyperlipidemic activity of p-coumaric acid in diabetic rats, role of pancreatic GLUT 2: In vivo approach. AB - P-coumaric acid (p-CA, 3-[4-hydroxyphenyl]-2-propenoic acid), the major component widely found in nutritious plant foods, has various antioxidant, antiinflammatory and anticancer property. To evaluate the antidiabetic and antihyperlipidemic mechanisms, via the effects on carbohydrate, lipids and lipoproteins responses in adult male albino Wistar rats were examined by treated with p-CA. Rats were injected with streptozotocin (STZ, 40mg/kg b.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus. Diabetic rats were treated with p-CA orally at a dose of 100mg/kg b.w. The potential defending character of p-CA against diabetic rats was evaluated by performing the various biochemical parameters and glucose transporter such as GLUT2 mRNA expression of pancreas. Administration of p-CA significantly lowers the blood glucose level, gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6 bisphosphatase whereas increases the activities of hexokinase, glucose-6 phosphatase dehydrogenase and GSH via by increasing level of insulin. p-CA reduces the total cholesterol and triglycerides in both plasma and tissues i.e. liver and kidney. p-CA also decreases the LDL-C, VLDL-C and it considerably increase the level of HDL-C. A significant decreased expression of GLUT 2 mRNA in the pancreas was recorded in the supplementation of p-CA treated groups. Taken together, these results suggest that p-CA modulates glucose and lipid metabolism via GLUT 2 activation in the pancreatic and has potentially beneficial effects in improving or treating metabolic disorders. PMID- 27662475 TI - No Evidence of Trade-Off between Farm Efficiency and Resilience: Dependence of Resource-Use Efficiency on Land-Use Diversity. AB - Efficiency in the use of resources stream-lined for expected conditions could lead to reduced system diversity and consequently endanger resilience. We tested the hypothesis of a trade-off between farm resource-use efficiency and land-use diversity. We applied stochastic frontier production models to assess the dependence of resource-use-efficiency on land-use diversity as illustrated by the Shannon-Weaver index. Total revenue in relation to use of capital, land and labour on the farms in Southern Finland with a size exceeding 30 ha was studied. The data were extracted from the Finnish Profitability Bookkeeping data. Our results indicate that there is either no trade-off or a negligible trade-off of no economic importance. The small dependence of resource-use efficiency on land use diversity can be positive as well as negative. We conclude that diversification as a strategy to enhance farm resilience does not necessarily constrain resource-use efficiency. PMID- 27662474 TI - Inhibition of eukaryotic initiation factor 4E phosphorylation by cercosporamide selectively suppresses angiogenesis, growth and survival of human hepatocellular carcinoma. AB - Mnk kinase is required for the phosphorylation and activation of the eukaryotic initiation factor 4E (eIF4E), which regulates translation of proteins involve in important aspects of hepatocellular carcinoma (HCC). Here we investigated whether an antifungal agent, cercosporamide, which had been recently identified as a potent Mnk inhibitor, is active against HCC and angiogenesis. We showed that cercosporamide significantly inhibited growth and induced caspase-dependent apoptosis on numerous HCC cell lines, while sparing normal liver cells. In addition, cercosporamide impaired HCC angiogenesis via inhibiting HCC-endothelial cells (HCC-EC) capillary network formation, migration, proliferation and survival. Importantly, cercosporamide sensitized HCC cells to cisplatin in in vitro cell culture and in vivo HCC xenograft mouse model. Cercosporamide blocked the phosphorylation of eIF4E but not Erk or p38 in a dose- and time-dependent manner in HCC and HCC-EC cells, suggesting that suppression of eIF4E phosphorylation was the result of inhibition of Mnk but not Mnk upstream pathways. Overexpression of constitutively active eIF4E (S209D) but not the nonphosphorylatable eIF4E (S209A) abolished the inhibitory effects of cercosporamide in HepG2 cells. Altogether, our work demonstrates that cercosporamide acts as a Mnk inhibitor through blockage of eIF4E phosphorylation and selectively exhibits anti-HCC activities. Our work suggests that targeting MNK-eIF4E pathway represents a therapeutic strategy to overcome chemo-resistance for HCC treatment. PMID- 27662476 TI - The Application of Liquid Nitrogen Spray Cryotherapy in Treatment of Bronchial Stenosis. AB - OBJECTIVE: Spray cryotherapy (SCT), the application of liquid nitrogen in a noncontact form, has been demonstrated to have efficacy in treating various types of pathologic lesions of the airway when used as an adjunct with bronchoscopy. The purpose of the study was to evaluate the results of the use of bronchoscopic SCT on the airway in a single institution. METHODS: We performed a retrospective review of data collected on all patients who underwent SCT to re-establish or improve airway patency in an 11-month period. Patients were classified based on the nature of their disease into benign or malignant. Demographic data, change in luminal patency, and clinical outcomes were recorded. The percent of stenosis was divided into grades according to the following classification: 1, <=25%; 2, 26% to 50%; 3, 51% to 75%; and 4, >=76%. We defined successful completion of treatment as obtaining a final patency of grade 1. RESULTS: Twenty-two patients met inclusion criteria, with 45.5% (10 patients) having benign stenosis and 54.5% (12 patients) malignant. At initial bronchoscopic evaluation, the median grade of stenosis was 4 for malignant disease and 3.5 for benign disease. The median final posttreatment grade of stenosis was 2 for malignant disease and 1 for benign. The median improvement in grade of stenosis after treatment was 2 for both malignant and benign causes (Wilcoxon test, P = 0.92). Final patency of grade 1 was achieved in 42% of malignant stenosis and 80% of benign. Overall, 86.4% of patients had an improvement in grade of stenosis after treatment. The rate of morbidity was 4.5% (1/22) of all patients. CONCLUSIONS: The median change in grade after treatment was 2 grades of improvement for both the benign and malignant groups. These results provide evidence that the use of SCT is equally efficacious for both types of stenosis with an expectation of overall improvement in luminal patency, offering a safe and effective method of achieving airway patency in a minimally invasive fashion. This study contributes to the small but growing body of literature supporting the use of SCT in benign and malignant disease. PMID- 27662477 TI - Transcatheter Aortic Valve Replacement: Current Technology and Future Directions. AB - Transcatheter aortic valve replacement as an alternative to open surgical repair is rapidly becoming more used in high-risk patients with aortic stenosis. Transcatheter aortic valve replacement offers the benefit of being much less invasive than traditional surgical repair and has evolved as a therapeutic option for patients with prohibitive surgical risk or those deemed surgically inoperable. Nevertheless, despite its potential to mitigate risk in this frail population, it comes with its own unique set of complications. Technological advancements in valve structure, function, and delivery have and continue to attempt to minimize these risks. This review aims to summarize current advancements in transcatheter aortic valve replacement technology while also introducing areas of future direction in this exciting new field. PMID- 27662480 TI - Band structure calculation of SH waves in nanoscale multilayered piezoelectric phononic crystals using radial basis function method with consideration of nonlocal interface effects. AB - In this paper, the radial basis function (RBF) collocation method based on the nonlocal Eringen piezoelectricity theory is developed to compute the band structures of nanoscale multilayered piezoelectric phononic crystals taking account of nonlocal interface effects. Detailed calculations are performed for anti-plane transverse waves propagating obliquely or vertically in the system. The correctness of the present method is verified by comparing the numerical results with those obtained by applying the transfer matrix method in the case of nonlocal perfect interfaces. The effects of nonlocal interface imperfections are considered by comparing with the nonlocal perfect interfaces. In addition, the influences of the piezoelectric constant, the nanoscale size, the impedance ratio and the incidence angle on the cut-off frequency and band structures are investigated and discussed in detail. Numerical results show that the nonlocal interface discontinuity has more obvious effect on the low-frequency band structures at the microscopic scale than at the macroscopic scale. Furthermore, at the macroscopic scale, the nonlocal interface imperfection has an obvious effect on the high frequency waves, but the effect on the low frequency waves is not obvious, and the nonlocal interface imperfection has no effect on the cut-off frequency at the microscopic scale. PMID- 27662478 TI - Minimally Invasive Mitral Valve Surgery III: Training and Robotic-Assisted Approaches. AB - Minimally invasive mitral valve operations are increasingly common in the United States, but robotic-assisted approaches have not been widely adopted for a variety of reasons. This expert opinion reviews the state of the art and defines best practices, training, and techniques for developing a successful robotics program. PMID- 27662479 TI - Differential Rickettsial Transcription in Bloodfeeding and Non-Bloodfeeding Arthropod Hosts. AB - Crucial factors influencing the epidemiology of Rickettsia felis rickettsiosis include pathogenesis and transmission. Detection of R. felis DNA in a number of arthropod species has been reported, with characterized isolates, R. felis strain LSU and strain LSU-Lb, generated from the cat flea, Ctenocephalides felis, and the non-hematophagous booklouse, Liposcelis bostrychophila, respectively. While it is realized that strain influence on host biology varies, the rickettsial response to these distinct host environments remained undefined. To identify a panel of potential rickettsial transmission determinants in the cat flea, the transcriptional profile for these two strains of R. felis were compared in their arthropod hosts using RNAseq. Rickettsial genes with increased transcription in the flea as compared to the booklouse were identified. Genes previously associated with bacterial virulence including LPS biosynthesis, Type IV secretion system, ABC transporters, and a toxin-antitoxin system were selected for further study. Transcription of putative virulence-associated genes was determined in a flea infection bioassay for both strains of R. felis. A host-dependent transcriptional profile during bloodfeeding, specifically, an increased expression of selected transcripts in newly infected cat fleas and flea feces was detected when compared to arthropod cell culture and incubation in vertebrate blood. Together, these studies have identified novel, host-dependent rickettsial factors that likely contribute to successful horizontal transmission by bloodfeeding arthropods. PMID- 27662482 TI - Functional abnormalities of the right posterior insula are related to the altered self-experience in schizophrenia. AB - The insula is involved in detecting the salience of internal and external stimuli, and it plays a critical role in psychosis. Previous studies have demonstrated the structural and functional alterations of the insula in schizophrenia. To acquire a full picture of the functional alterations of the insula in schizophrenia, the resting-state fMRI data of 46 patients with schizophrenia and 46 healthy control subjects were collected. We used clustering analysis to divide the insula into three subregions: the dorsal anterior insula (dAI), ventral anterior insula (vAI) and posterior insula (PI). Then, whole-brain functional connectivity analysis was conducted based on these subregions. The results showed that the right dAI and PI in patients exhibited altered functional connections with the primary sensorimotor area. In addition, the right PI of the patients exhibited increased functional correlations with the thalamus. More importantly, the altered functional properties of the right PI were significantly correlated with the severity of the delusion and poor insight in schizophrenia. The results suggested that the right PI might play an important role in self experience processing in schizophrenia. Accordingly, the right PI should be considered very important in the pathological mechanism of schizophrenia. PMID- 27662481 TI - The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons. AB - Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons. PMID- 27662483 TI - In shoe pressure measurements during different motor tasks while wearing safety shoes: The effect of custom made insoles vs. prefabricated and off-the-shelf. AB - Health and safety regulations in many countries require workers at risk to wear safety shoes in a factory environment. These shoes are often heavy, rigid, and uncomfortable. Wearing safety shoes daily leads to foot problems, discomfort and fatigue, resulting also in the loss of numerous working days. Currently, knowledge of the biomechanical effects of insoles in safety shoes, during working activities, is very limited. Seventeen workers from a metalworking factory were selected and clinically examined for any foot conditions. Workers feet were 3D scanned, with regards to their plantar view, and the images used to design 34 custom-insoles, based on foot and safety shoe models. Three insoles were blind tested by each worker: custom (CUS); prefabricated with the safety-shoe (PSS), and off-the-shelf (OTS). Foot-to-insole pressure distribution was measured in seven motor tasks replicating typical working activities: single and double-leg standing; weight lifting; stair ascending and descending; normal and fast walking. Wearing CUS within safety shoes resulted in a greater uniform pressure distribution across plantar regions for most of the working activities. Peak pressure at the forefoot during normal walking was the lowest in the custom insole (CUS 275.9+/-55.3kPa; OTS 332.7+/-75.5kPa; PSS 304.5+/-54.2kPa). Normal and fast walking were found to be the most demanding activities in terms of peak pressure. Wearing safety shoes results in high pedobarographic parameters in several foot regions. The use of custom insoles designed on the foot morphology helps decrease peak pressure and pressure-time integral compared to prefabricated featureless insoles. PMID- 27662484 TI - Sole-parent work schedules and adolescent wellbeing:Evidence from Australia. AB - Extensive evidence has shown that working nonstandard hours, such as evening or night shifts, impacts negatively on workers' own health, and a growing literature suggests such impacts extend to the health of workers' children. Using matched parent and child data from a large Australian panel survey this paper explores the effects of parental work schedules on the mental and physical health of adolescents aged 15-20 in sole-parent families. Random-effects models indicate adolescents have marginally worse emotional and physical health when their parent works nonstandard hours, based on SF-36 component summary scores, associated primarily with emotional or physical role limitations. Parental weekend schedules are particularly detrimental to adolescent physical health. Evidence is found that the effects of nonstandard work schedules on adolescent wellbeing are transmitted through increased work-family conflict and exacerbated where parents have low job control. PMID- 27662485 TI - What is the future of research on medical decision making? (And is it bright?): A response to Drewniak and colleagues. PMID- 27662486 TI - Knockdown of Tripartite-59 (TRIM59) Inhibits Cellular Proliferation and Migration in Human Cervical Cancer Cells. AB - The tripartite motif (TRIM) family of proteins is a class of highly conservative proteins that have been implicated in multiple processes. TRIM59, one member of the TRIM family, has now received recognition as a key regulator in the development and progression of human diseases. However, its role in human tumorigenesis has remained largely unknown. In this study, the effects of TRIM59 expression on cell proliferation and migration were investigated in human cervical cancer cells. The expression of TRIM59 in clinical cervical cancer tissues and cervical cancer cells was initially determined by RT-PCR and Western blot. Specific shRNA against TRIM59 was then employed to knock down the expression of TRIM59 in cervical cancer lines HeLa and SiHa. The effects of TRIM59 knockdown on cell proliferation was assessed by MTT assay and colony formation assay. Transwell assay was conducted to reveal cell migration and invasion abilities before and after TRIM59 knockdown. Our results showed that the expression of TRIM59 was significantly elevated in cervical cancers. Knockdown of TRIM59 significantly inhibited cell proliferation and colony formation as well as cell migration and invasion abilities in cervical cancer HeLa and SiHa cells. Cell cycle progression analysis showed that TRIM59-depleted cells preferred to accumulate in the S phase. These data suggest that TRIM59 is a potential target that promotes the progression of cervical cancer. PMID- 27662488 TI - Evaluation of Basketball-Specific Agility: Applicability of Preplanned and Nonplanned Agility Performances for Differentiating Playing Positions and Playing Levels. AB - Sekulic, D, Pehar, M, Krolo, A, Spasic, M, Uljevic, O, Calleja-Gonzalez, J, and Sattler, T. Evaluation of basketball-specific agility: applicability of preplanned and nonplanned agility performances for differentiating playing positions and playing levels. J Strength Cond Res 31(8): 2278-2288, 2017-The importance of agility in basketball is well known, but there is an evident lack of studies examining basketball-specific agility performances in high-level players. The aim of this study was to determine the reliability and discriminative validity of 1 standard agility test (test of preplanned agility [change-of-direction speed] over T course, T-TEST), and 4 newly developed basketball-specific agility tests, in defining playing positions and performance levels in basketball. The study comprised 110 high-level male basketball players (height: 194.92 +/- 8.09 cm; body mass: 89.33 +/- 10.91 kg; age: 21.58 +/- 3.92 years). The variables included playing position (Guard, Forward, Center), performance level (first division vs. second division), anthropometrics (body height, body mass, and percentage of body fat), T-TEST, nonplanned basketball agility test performed on dominant (BBAGILdom) and nondominant sides (BBAGILnond), and a preplanned (change-of-direction speed) basketball agility test performed on dominant (BBCODSdom) and nondominant sides (BBCODSnond). The reliability of agility tests was high (intraclass correlation coefficient of 0.81 0.95). Forwards were most successful in the T-TEST (F test: 13.57; p = 0.01). Guards outperformed Centers in BBCODSdom, BBCODSndom, BBAGILdom, and BBAGILnond (F test: 5.06, p = 0.01; 6.57, 0.01; 6.26, 0.01; 3.37, 0.04, respectively). First division Guards achieved better results than second division Guards in BBCODSdom (t: 2.55; p = 0.02; moderate effect size differences), BBAGILdom, and BBAGILnond (t: 3.04 and 3.06, respectively; both p = 0.01 and moderate effect size differences). First division Centers outperformed second division Centers in BBAGILdom (t: 2.50; p = 0.02; moderate effect size differences). The developed basketball-specific agility tests are applicable when defining position-specific agility. Both preplanned and nonplanned agilities are important qualities in differentiating between Guards of 2 performance levels. The results confirmed the importance of testing basketball-specific nonplanned agility when evaluating the performance level of Centers. PMID- 27662489 TI - Effects of Two Different Volume-Equated Weekly Distributed Short-Term Plyometric Training Programs on Futsal Players' Physical Performance. AB - Yanci, J, Castillo, D, Iturricastillo, A, Ayarra, R, and Nakamura, FY. Effects of two different volume-equated weekly distributed short-term plyometric training programs on futsal players' physical performance. J Strength Cond Res 31(7): 1787 1794, 2017-The aim was to analyze the effect of 2 different plyometric training programs (i.e., 1 vs. 2 sessions per week, same total weekly volume) on physical performance in futsal players. Forty-four futsal players were divided into 3 training groups differing in weekly plyometric training load: the 2 days per week plyometric training group (PT2D, n = 15), the 1 day per week plyometric training group (PT1D, n = 12), and the control group (CG, n = 12) which did not perform plyometric training. The results of this study showed that in-season futsal training per se was capable of improving repeat sprint ability (RSA) (effect size [ES] = -0.59 to -1.53). However, while change of direction ability (CODA) was maintained during the training period (ES = 0.00), 15-m sprint (ES = 0.73), and vertical jump (VJ) performance (ES = -0.30 to -1.37) were significantly impaired. By contrast, PT2D and PT1D plyometric training were effective in improving futsal players' 15-m sprint (ES = -0.64 to -1.00), CODA (ES = -1.83 to -5.50), and horizontal jump (ES = 0.33-0.64) performance. Nonetheless, all groups (i.e., PT2D, PT1D, and CG) presented a reduction in VJ performance (ES = -0.04 to 1.37). Regarding RSA performance, PT1D showed a similar improvement compared with CG (ES = -0.65 to -1.53) after the training intervention, whereas PT2D did not show significant change (ES = -0.04 to -0.38). These results may have considerable practical relevance for the optimal design of plyometric training programs for futsal players, given that a 1-day-per-week plyometric training program is more efficient than a 2-day-per-week plyometric training program to improve the futsal players' physical performance. PMID- 27662487 TI - LMethyR-SVM: Predict Human Enhancers Using Low Methylated Regions based on Weighted Support Vector Machines. AB - BACKGROUND: The identification of enhancers is a challenging task. Various types of epigenetic information including histone modification have been utilized in the construction of enhancer prediction models based on a diverse panel of machine learning schemes. However, DNA methylation profiles generated from the whole genome bisulfite sequencing (WGBS) have not been fully explored for their potential in enhancer prediction despite the fact that low methylated regions (LMRs) have been implied to be distal active regulatory regions. METHOD: In this work, we propose a prediction framework, LMethyR-SVM, using LMRs identified from cell-type-specific WGBS DNA methylation profiles and a weighted support vector machine learning framework. In LMethyR-SVM, the set of cell-type-specific LMRs is further divided into three sets: reliable positive, like positive and likely negative, according to their resemblance to a small set of experimentally validated enhancers in the VISTA database based on an estimated non-parametric density distribution. Then, the prediction model is obtained by solving a weighted support vector machine. RESULTS: We demonstrate the performance of LMethyR-SVM by using the WGBS DNA methylation profiles derived from the human embryonic stem cell type (H1) and the fetal lung fibroblast cell type (IMR90). The predicted enhancers are highly conserved with a reasonable validation rate based on a set of commonly used positive markers including transcription factors, p300 binding and DNase-I hypersensitive sites. In addition, we show evidence that the large fraction of the LMethyR-SVM predicted enhancers are not predicted by ChromHMM in H1 cell type and they are more enriched for the FANTOM5 enhancers. CONCLUSION: Our work suggests that low methylated regions detected from the WGBS data are useful as complementary resources to histone modification marks in developing models for the prediction of cell-type-specific enhancers. PMID- 27662490 TI - Repeated-Sprint Sequences During Female Soccer Matches Using Fixed and Individual Speed Thresholds. AB - Nakamura, FY, Pereira, LA, Loturco, I, Rosseti, M, Moura, FA, and Bradley, PS. Repeated-sprint sequences during female soccer matches using fixed and individual speed thresholds. J Strength Cond Res 31(7): 1802-1810, 2017-The main objective of this study was to characterize the occurrence of single sprint and repeated sprint sequences (RSS) during elite female soccer matches, using fixed (20 km.h) and individually based speed thresholds (>90% of the mean speed from a 20-m sprint test). Eleven elite female soccer players from the same team participated in the study. All players performed a 20-m linear sprint test, and were assessed in up to 10 official matches using Global Positioning System technology. Magnitude-based inferences were used to test for meaningful differences. Results revealed that irrespective of adopting fixed or individual speed thresholds, female players produced only a few RSS during matches (2.3 +/- 2.4 sequences using the fixed threshold and 3.3 +/- 3.0 sequences using the individually based threshold), with most sequences composing of just 2 sprints. Additionally, central defenders performed fewer sprints (10.2 +/- 4.1) than other positions (fullbacks: 28.1 +/- 5.5; midfielders: 21.9 +/- 10.5; forwards: 31.9 +/- 11.1; with the differences being likely to almost certainly associated with effect sizes ranging from 1.65 to 2.72), and sprinting ability declined in the second half. The data do not support the notion that RSS occurs frequently during soccer matches in female players, irrespective of using fixed or individual speed thresholds to define sprint occurrence. However, repeated-sprint ability development cannot be ruled out from soccer training programs because of its association with match-related performance. PMID- 27662491 TI - Acute Physiological Responses to Moderate-Load Resistance Exercise in Hypoxia. AB - Scott, BR, Slattery, KM, Sculley, DV, Lockhart, C, and Dascombe, BJ. Acute physiological responses to moderate-load resistance exercise in hypoxia. J Strength Cond Res 31(7): 1973-1981, 2017-This study assessed whether hypoxia augments anabolic responses to moderate-load resistance exercise. Fourteen trained men performed moderate-load resistance exercise in normoxia (NORM; fraction of inspired oxygen [FIO2] = 21%) and moderate-level hypoxia (MH; FIO2 = 16%). Exercise comprised 3 sets of 10 repetitions of squats and deadlifts at 60% of 1 repetition maximum, with 60-second interset rest. Blood lactate (BLa) was quantified after each exercise, whereas arterial oxygen saturation and heart rate (HR) were assessed after each set. Thigh circumference was measured before and after exercise. Muscle activation and oxygenation were monitored by surface electromyography (EMG) and near-infrared spectroscopy, respectively. Relative BLa concentrations were significantly higher following squats (p = 0.041) and deadlifts (p = 0.002) in MH than NORM. Arterial oxygen saturation was lower after each set in MH compared with NORM (p < 0.001), although HR and thigh circumference were not different between conditions. Integrated EMG was higher in MH than in NORM for the squat during several repetitions (p <= 0.032). Measures of muscle oxygen status were not significantly different between conditions (p >= 0.247). The main findings from this study suggest that hypoxia during moderate load resistance exercise augments metabolite accumulation and muscle activation. However, a significant hypoxic dose was not measured at the muscle, possibly because of the moderate level of hypoxia used. The current data support previous hypotheses that have suggested hypoxia can augment some physiological responses that are important for muscular development, and may therefore provide benefit over the equivalent training in normoxia. PMID- 27662492 TI - Mycoplasma agalactiae Induces Cytopathic Effects in Infected Cells Cultured In Vitro. AB - Mycoplasma agalactiae is the etiological agent of the contagious agalactia syndrome in sheep and goats and causes significant economic losses worldwide. Yet the mechanism of pathogenesis is largely unknown. Even whole-genome sequence analysis of its pathogenic type strain did not lead to any conclusions regarding its virulence or pathogenicity factors. Although inflammation and tissue destruction at the local site of M. agalactiae infection are largely considered as effects of the host immune response, the direct effect of the agent on host cells is not completely understood. The aim of this study was to investigate the effect of M. agalactiae infection on the quality and viability of host cells in vitro. Changes in cell morphology including cell elongation, cytoplasm shrinkage and membrane blebbing were observed in infected HeLa cells. Chromatin condensation and increased caspase-3 cleavage in infected HeLa cells 48 h after infection suggests an apoptosis-like phenomenon in M. agalactiae-infected cells. In compliance with these results, decreased viability and cell lysis of M. agalactiae-infected HeLa cells was also observed. Measurement of the amount of LDH released after M. agalactiae infection revealed a time- and dose-dependent increase in HeLa cell lysis. A significant decrease in LDH released after gentamicin treatment of infected cells confirmed the major role of cytadherent M. agalactiae in inducing host cell lysis. This is the first study illustrating M. agalactiae's induction of cytopathic effects in infected HeLa cells. Further detailed investigation of infected host tissue for apoptotic markers might demonstrate the association between M. agalactiae-induced host cell lysis and the tissue destruction observed during M. agalactiae natural infection. PMID- 27662493 TI - Air quality perception of pedestrians in an urban outdoor Mediterranean environment: A field survey approach. AB - Perception plays a significant role on people's response to preventive measures. In the view of public awareness, the aim of this study was to explore factors that affect air quality perception and to reveal its potential patterns. Air quality perception of individuals, in terms of dust and overall air quality, was examined in relation to air pollutants concentrations, meteorological variables, personal characteristics as well as their thermal sensation and health condition. The data used were obtained from environmental measurements, in situ and from stations, and questionnaire surveys conducted in an outdoor urban Mediterranean area, Athens, Greece. The participants were asked to report their air quality perception and thermal sensation based on predefined scales. A thermal index, Physiological Equivalent Temperature (PET), was estimated to obtain an objective measure of thermal sensation. Particulate matter (PM10) and nitrogen oxide (NO) were associated with dust perception. Nitrogen oxides (NOx) and carbon monoxide (CO) were associated to air quality perception. Age, area of residence, health symptoms and thermal sensation also affected the perception of air quality. Dusty or poor air quality conditions were more likely to be reported when pollutants' concentrations were increased. Younger people, participants residing in the city center, experiencing health symptoms or warm thermal sensation showed a trend towards reporting more unfavorable air quality conditions. PMID- 27662494 TI - Freshwater mussels in an urban watershed: Impacts of anthropogenic inputs and habitat alterations on populations. AB - The substantial increase in urbanization worldwide has resulted in higher emissions of wastewater to riverine systems near urban centers, which often impairs aquatic populations and communities. This study examined the effect of urbanization on freshwater mussel populations, including Species at Risk in two rivers receiving wastewater. The influence of anthropogenic activities was assessed in a watershed in the Laurentian Great Lakes basin, one that historically supported one of the most diverse mussel faunas in Canada. In the Grand River (ON), four sites along a 60km reach spanning from an upstream reference site to an urban-impacted downstream area were examined. In the Speed River, mussel populations at six sites along a 10km reach, selected to bracket specific anthropogenic inputs and structures were assessed. A semi-quantitative visual search method revealed that catch per unit effort in the Grand River declined by >60% from the upstream reference site to the area downstream of an urban center. The size (length) frequency distribution of the most abundant species, Lasmigona costata, was significantly (p<=0.008) different upstream of the majority of urban inputs (45-130mm) compared to downstream of the cities (85 115mm). In the Speed River, impoundments and wastewater treatment plants (WWTP) reduced both the diversity and catch per effort. Most striking were 84 and 95% changes in the number of mussels found on either side of two impoundments, and a 98% drop in mussels immediately downstream of a WWTP outfall. These population level effects of decreased abundance and underrepresentation of smaller mussels downstream of the urban area correspond to previously documented impacts at the biochemical and whole organism level of biological organization in wild mussels at this location. Our results demonstrate that poor water quality and physical barriers in urban environments continue to impair susceptible populations and communities of aquatic animals. PMID- 27662495 TI - Acupuncture Increases the Excitability of the Cortico-Spinal System in Patients with Chronic Disorders of Consciousness Following Traumatic Brain Injury. AB - OBJECTIVE: To evaluate the immediate effect of acupuncture on cortico spinal tract (CST) activity in patients with chronic disorders of consciousness (DOC) after traumatic brain injury (TBI) by measuring motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS). DESIGN: Changes in several variables in the acupuncture session were compared with those in the control session without acupuncture in the same patients. SETTING: Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Gifu, Japan. PATIENTS: Fourteen patients (mean age +/- standard deviation, 39 +/- 17 years; 12 men) with chronic DOC (5 in a vegetative state and 9 in a minimally conscious state) following severe TBI. INTERVENTION: Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes. OUTCOME MEASURES: Main outcome measure was MEP amplitude. MEP amplitude, measured by using TMS on the primary motor cortex, was recorded from the abductor pollicis brevis muscle. MEP recordings were performed before acupuncture (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). As a control, the same procedure without acupuncture was performed on another day with the order randomized. MEP amplitude and latency were calculated. Evoked F-wave measurements were also performed to calculate maximum M-wave amplitude (Mmax), M-wave latency, and F-wave latency in the same muscle. Central motor conduction time (CMCT) and MEP/Mmax ratio were also calculated from the MEP and F-wave measurement data. RESULTS: MEP amplitude and MEP/Mmax were increased significantly in the acupuncture session at phases 1 and 2 compared with the control session (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). CMCTs were reduced at phases 1 and 2 in the acupuncture session compared with the control session, and the change at phase 1 was statistically significant (P = 0.002). CONCLUSIONS: Acupuncture treatment increased the CST activity of patients with chronic DOC after severe TBI. PMID- 27662496 TI - Acute gastrointestinal bleeding cases presenting to the emergency department are associated with age, sex and seasonal and circadian factors. AB - BACKGROUND: Gastrointestinal bleeding (GIB) is one of the most common emergencies in gastroenterology. The aim of this study was to investigate the association between the incidence of GIB and seasonal, circadian and meteorological patterns in the emergency department (ED) of a tertiary hospital. PATIENTS AND METHODS: From January 2007 until December 2012, we retrospectively evaluated patients presenting to the ED with respect to the number and location of GIB, season, time of day and weather. RESULTS: Of 45 458 patients, 578 (1.3%) presented with a GIB. Of these, 62.5% were men compared with 54.7% of all patients in the ED (chi, P=0.0002). Patients with GIB were on average 4.4 years older than those without GIB (95% confidence interval 2.76-5.98, t-test, P<0.001). In addition, 304 (52.6%) patients had upper GIB and 138 (23.9%) had lower GIB. In total, 136 (23.5%) patients required no endoscopy because of initial laboratory and circulatory stability. In univariate analysis, meteorological parameters, including air temperature, cloud cover, relative humidity, vapour pressure, amount of precipitation, sunshine duration and snow height, were each associated with an increased risk of acute GIB (all P-values<0.05). In the 6-year study period, patients with GIB presented to the ED mainly during the winter months. Independent predictors of GIB on multivariate logistic regression were older age, male sex, season and daytime, all P less than 0.005. Emergency admissions during the night were associated with a 54 and 35% higher risk of GIB compared with daytime (8 a.m. to 4 p.m., P=0.0002) and late evening hours (4 p.m. to midnight, P=0.0142), respectively. CONCLUSION: Presentation of patients with acute GIB in the ED is age and sex specific and shows seasonal and circadian differences in distribution, with an increased incidence in winter months and during night-time. This should be considered when determining possible emergency endoscopic interventions and the availability of emergency endoscopy services. PMID- 27662497 TI - Diagnostic accuracy of confocal laser endomicroscopy for the characterization of liver nodules. AB - OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is a promising new imaging technique enabling in-vivo analysis of tissues at the cellular level, in real time. The aim of the present study was to prospectively evaluate the feasibility and accuracy of indocyanine green-aided pCLE for the diagnosis of malignant liver nodules. PATIENTS AND METHODS: From October 2014 to July 2015, liver specimens from 30 consecutive patients were analyzed ex vivo using pCLE directly after resection, with indocyanine green as contrast agent. The final diagnosis was obtained histologically, as per standard of care. In phase 1, a pathologist and a physicist established pCLE image criteria to distinguish normal parenchyma, malignant nodules, and metastases that had completely responded to chemotherapy. In phase 2, a pathologist and a surgeon reviewed selected videos retrospectively to assess the effectiveness of these. RESULTS: In phase 1, the healthy nodules were characterized by fluorescent hepatocytes with nonfluorescent nuclei and the malignant nodules were identified as strongly fluorescent, irregular cancer-cell clusters. The extracellular matrix was substantially less fluorescent compared with the cancerous clusters of cells. After chemotherapy, a very dense and strongly fluorescent fibrosis replaced tubular structures of cancerous cells. The retrospective evaluation in phase 2 resulted in 78 and 100% sensitivity, 100 and 89% specificity, 90 and 100% positive predictive value, and 90 and 100% negative predictive value for the surgeon and the pathologist, respectively, for the detection of malignant nodules. CONCLUSION: This series emphasized that characterization of liver metastases is possible with pCLE, with high performance results. PMID- 27662498 TI - Nano-Cesium for Anti-Cancer Properties: An Investigation into Cesium Induced Metabolic Interference. AB - The use of cesium chloride (CsCl) for cancer therapy ("high pH therapy") has been theorized to produce anticancer properties by raising intracellular pH to induce apoptosis. Although considered as "alternative medicine", little scientific evidence supports this theory. Alternatively, cells have no cesium ion (Cs+) mediated channels for clearance. Thus, such unstable electrochemical distributions have the severe potential to disrupt electrochemical dependent cellular processes, such as glucose cotransporters. Hence, a detailed investigation of pH changing effects and glucose uptake inhibition are warranted as a possible cesium-induced anticancer therapy. We developed and characterized cesium nanoparticles (38 +/- 6 nm), termed NanoCs, for nanoparticle-mediated internalization of the ion, and compared its treatment to free CsCl. Our investigations suggest that neither NanoCs nor CsCl drastically changed the intracellular pH, negating the theory. Alternatively, NanoCs lead to a significant decrease in glucose uptake when compared to free CsCl, suggesting cesium inhibited glucose uptake. An apoptosis assay of observed cell death affirms that NanoCs leads tumor cells to initiate apoptosis rather than follow necrotic behavior. Furthermore, NanoCs lead to in vivo tumor regression, where H&E analysis confirmed apoptotic cell populations. Thus, NanoCs performed pH independent anticancer therapy by inducing metabolic stasis. PMID- 27662499 TI - Exploration of Structural Frameworks for Reactive and Enantioselective Peptide Catalysts by Library Screenings. AB - By screening large-scale N-terminal l-prolyl peptide libraries, we explored efficient catalysts for asymmetric Michael addition of a malonate to an enal. The catalytically active peptides obtained by the screening could be categorized into two groups based on the similarity of amino acid sequences. One group of the peptides selectively gave an S-product, whereas the other gave an R-product, despite all of the peptides having a common N-terminal sequence, Pro-d-Pro. Further optimization by second-generation screenings afforded more reactive and enantioselective catalysts. It was found that the peptides having a histidine residue at the seventh position were good catalysts, and their reaction efficiencies were correlated with the abilities of entrapping a substrate into resin beads. PMID- 27662500 TI - Second Virial Coefficient As Determined from Protein Phase Behavior. AB - We quantitatively link the macroscopic phase behavior of protein solutions to protein-protein interactions based on a coarse-grained colloidal approach. We exploit the extended law of corresponding states and apply the Derjaguin-Landau Verwey-Overbeek (DLVO) theory in order to infer the second virial coefficient b2, an integral measure of the interaction potential, from the phase behavior, namely, cloud-point temperature (CPT) measurements under conditions favoring protein crystallization. This determination of b2 yields values that quantitatively agree with the results of static light scattering (SLS) experiments. The strength of the attractions is quantified in terms of an effective Hamaker constant, which accounts for van der Waals attractions as well as non-DLVO forces, such as hydration and hydrophobic interactions. Our approach based on simple lab experiments to determine the CPT in combination with the DLVO theory is expected to facilitate further biophysical research on protein-protein interactions in complex solution environments. PMID- 27662501 TI - Kaposi sarcoma herpesvirus-associated cancers and related diseases. AB - PURPOSE OF REVIEW: This review discusses the pathogenesis and recent advances in the management of Kaposi sarcoma herpesvirus (KSHV)-associated diseases. RECENT FINDINGS: KSHV, a gammaherpesvirus, causes several tumors and related diseases, including Kaposi sarcoma, a form of multicentric Castleman disease (KSHV-MCD), and primary effusion lymphoma. These most often develop in patients infected with human immunodeficiency virus (HIV). KSHV inflammatory cytokine syndrome (KICS) is a newly described syndrome with high mortality that has inflammatory symptoms like MCD but not the pathologic lymph node findings. KSHV-associated diseases are often associated with dysregulated human interleukin-6, and KSHV encodes a viral interleukin-6, both of which contribute to disease pathogenesis. Treatment of HIV is important in HIV-infected patients. Strategies to prevent KSHV infection may reduce the incidence of these tumors. Pomalidomide, an immunomodulatory agent, has activity in Kaposi sarcoma. Rituximab is active in KSHV-MCD but can cause Kaposi sarcoma exacerbation; rituximab plus liposomal doxorubicin is useful to treat KSHV-MCD patients with concurrent Kaposi sarcoma. SUMMARY: KSHV is the etiological agents of all forms of Kaposi sarcoma and several other diseases. Strategies employing immunomodulatory agents, cytokine inhibition, and targeting of KSHV-infected cells are areas of active research. PMID- 27662502 TI - High Throughput Light Absorber Discovery, Part 2: Establishing Structure-Band Gap Energy Relationships. AB - Combinatorial materials science strategies have accelerated materials development in a variety of fields, and we extend these strategies to enable structure property mapping for light absorber materials, particularly in high order composition spaces. High throughput optical spectroscopy and synchrotron X-ray diffraction are combined to identify the optical properties of Bi-V-Fe oxides, leading to the identification of Bi4V1.5Fe0.5O10.5 as a light absorber with direct band gap near 2.7 eV. The strategic combination of experimental and data analysis techniques includes automated Tauc analysis to estimate band gap energies from the high throughput spectroscopy data, providing an automated platform for identifying new optical materials. PMID- 27662503 TI - Molecular Mechanisms of the Bindings between Non-Amyloid beta Component Oligomers and Amylin Oligomers. AB - It has been suggested that the connection between amyloidogenic diseases is related to the interactions between aggregates of amyloids, which are related to type 2 diabetes and Parkinson's disease. Herein, we illustrate the interactions between amylin oligomers and non-amyloid beta component (NAC) oligomers. Using molecular dynamics simulations and statistical calculations, we studied the mechanisms through which NAC oligomers interact with amylin oligomers to form NAC amylin hetero-oligomers. Our simulations have shown that there are more than one possible pathways, which form the NAC-amylin hetero-oligomers. Our structural analyses demonstrate that the interactions in the NAC-amylin hetero-oligomers do not affect the structural features of the NAC oligomers, but they do stabilize the structures of the amylin oligomers. Taken together, our results strongly support the hypothesis that NAC oligomers may interact with amylin oligomers through several pathways, of which some pathways are more preferred because of the structural stability of the cross-seeding NAC-amylin oligomers. PMID- 27662504 TI - Gated Photochromic System of Diarylethene with a Photon-Working Key. AB - Upon visible light irradiation, a thermally reversible photochromic acid generator merocyanine dye gives a proton to the dimethylamino group of a non photochromic diarylethene in acetonitrile. The protonation rendered the non photochromic diarylethene photochromic. Thus, the thermally irreversible photochromic nature of the diarylethene is activated without any physical contact or addition of any compound but only by photoirradiation to the merocyanine dye. PMID- 27662505 TI - High-Performance Polymer Solar Cells Realized by Regulating the Surface Properties of PEDOT:PSS Interlayer from Ionic Liquids. AB - Significant efforts have been dedicated to the interface engineering of organic photovoltaic device, suggesting that the performance and aging of the device are not only dependent on the active layer, but also governed by the interface with electrodes. In this work, controllable interfacial dipole and conductivity have been achieved in ionic liquids (ILs) modified poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). We conclude that an appropriate interfacial conductivity is as essential as the suitable work function for an efficient buffer layer. Through forming favorable dipoles for hole transportation and reducing the film resistance by [HOEMIm][HSO4] treatment, an averaged performance of 8.64% is obtained for OPVs based on PTB7:PC71BM bulk heterojunction with improved stability. However, the improvement of performance is inconspicuous for OPVs based on PTB7-Th:PC71BM bulk heterojunction due to the incompetent energy level of high concentration ILs-modified PEDOT:PSS. The enhanced in-plane conductivity will reduce shunt resistance, and produce a fake high short-circuit current density (Jsc) with a lower fill factor. We point out that the Jsc can be improved by decreasing series resistance; meanwhile, the accompanying reduced shunt resistance has an unfavorable effect on device performance. PMID- 27662506 TI - Metabolic profiles of planktonic and biofilm cells of Candida orthopsilosis. AB - AIM: This study aims to understand which Candida orthopsilosis protein aids fungus adaptation upon its switching from planktonic growth to biofilm. MATERIALS & METHODS: Ion mobility separation within mass spectrometry analysis combination were used. RESULTS: Proteins mapped for different biosynthetic pathways showed that selective ribosome autophagy might occur in biofilms. Glucose, used as a carbon source in the glycolytic flux, changed to glycogen and trehalose. CONCLUSION: Candida orthopsilosis expresses proteins that combine a variety of mechanisms to provide yeasts with the means to adjust the catalytic properties of enzymes. Adjustment of the enzymes helps modulate the biosynthesis/degradation rates of the available nutrients, in order to control and coordinate the metabolic pathways that enable cells to express an adequate response to nutrient availability. PMID- 27662507 TI - Long-term genotoxic effects in the hematopoietic system of prenatally X irradiated mice. AB - PURPOSE: To investigate the genotoxic effects of prenatal X-irradiation in mice and the possible presence of late genomic instability. MATERIALS AND METHODS: Pregnant mice were exposed to 0, 1 or 2 Gy at embryonic day 11.5. Blood smears were obtained from pups at birth and on post-natal day 11, 21, 42 and 140. Hematological data (diameter of erythrocytes, percentage of reticulocytes and Granulocyte-to-Lymphocyte ratio [GLR]) and genotoxicity (micronucleated erythrocytes, micronucleated reticulocytes, CREST-positive and negative micronuclei) were assessed. RESULTS: Prenatal irradiation caused perinatal reticulocytosis (which ended on postnatal day 11) and a dose-dependent increase of GLR (indicative of myeloid skewing) on postnatal days 42 and 140. Two temporally distinct genotoxic effects were observed: an early, acute damage (still detectable at birth and soon after) and a late, long-term damage. CONCLUSIONS: Increases in micronuclei frequencies and GLR observed from day 42 on are both ascribable to DNA damage. Time of appearance of this late effect may be linked to the shift of hematopoiesis from spleen to bone marrow and to cell extrinsic factor such as the microenvironment. This study confirms that ionizing radiation can induce long-term genotoxic effects in the hematopoietic system and shows that prenatal irradiation determines genomic instability in blood-forming tissues of adult mice. PMID- 27662508 TI - Economic and care considerations of Marfan syndrome. AB - INTRODUCTION: Marfan syndrome is a rare multisystem disease of the connective tissue, which affects multiple organ systems. advances in healthcare have doubled the life-expectancy of patients over the past three decades. to date, there is no comprehensive review that consolidates economic considerations and care for marfan patients. Areas covered: Present research suggests that there may be a link between treatment pattern, disease progression and economic costs of Marfan syndrome. It indicates that an early detection of the disease and preventive interventions achieve a dual aim. From a patient perspective, it may reduce the amount of emergency surgery or intervention, and inpatient stays. In addition, it slows disease progression, lowers lifestyle restrictions, reduces psychological stress, and improves health-related quality of life. Expert commentary: Early detection and preventive measures are likely to achieve a dual aim by simultaneously containing costs and reducing the number and length of inpatient stays. PMID- 27662509 TI - Long-term measurements using home audiometry with Bekesy's technique. AB - OBJECTIVE: To examine the efficacy of fixed-frequency Bekesy's home audiometry to assess hearing fluctuation and treatment outcomes in patients with subjectively fluctuating hearing loss. DESIGN: SMAPH, a software audiometry program for Windows, was installed and calibrated on laptop computers. Bekesy's audiometry was carried out daily in the patients' homes, using sound-attenuating earphones. STUDY SAMPLE: Seventeen patients with previously or currently subjectively fluctuating hearing loss. Five patients received of treatment for their conditions during the measurement period. RESULTS: Measurement periods ranged from 6 to 60 days. Varying degrees of compliance were seen, some patients measuring less than 50% of the days, others measuring every day. Based on their long-term measurements the patients were classified into three groups: patients with stable recordings, with fluctuating low-frequency hearing loss, or with fluctuating high-frequency hearing loss. In the patients with stable recordings, significant test-retest differences were seen below 10 dB at frequencies 0.125-8 kHz. CONCLUSIONS: Home audiometry with Bekesy's technique can be used to evaluate disease activity and to monitor hearing results after therapy. PMID- 27662511 TI - Molecular Dynamics Study of a Dual-Cation Ionomer Electrolyte. AB - The poly(N1222 )x Li1-x [AMPS] ionomer system (AMPS=2-acrylamido-2-methylpropane sulfonic acid) with dual cations has previously shown decoupled Li ion dynamics from polymer segmental motions, characterized by the glass-transition temperature, which can result in a conductive electrolyte material whilst retaining an appropriate modulus (i.e. stiffness) so that it can suppress dendrite formation, thereby improving safety when used in lithium-metal batteries. To understand this ion dynamics behavior, molecular dynamics techniques have been used in this work to simulate structure and dynamics in these materials. These simulations confirm that the Li ion transport is decoupled from the polymer particularly at intermediate N1222+ concentrations. At 50 mol % N1222+ concentration, the polymer backbone is more rigid than for higher N1222+ concentrations, but with increasing temperature Li ion dynamics are more significant than polymer or quaternary ammonium cation motions. Herein we suggest an ion-hopping mechanism for Li+ , arising from structural rearrangement of ionic clusters that could explain its decoupled behavior. Higher temperatures favor an aggregated ionic structure as well as enhancing these hopping motions. The simulations discussed here provide an atomic-level understanding of ion dynamics that could contribute to designing an improved ionomer with fast ion transport and mechanical robustness. PMID- 27662510 TI - Discriminating Between Fatigue and Sleepiness in the Naval Operational Environment. AB - OBJECTIVE: To assess the similarities and differences between reported levels of fatigue and sleepiness as a consequence of working at sea. PARTICIPANTS: 767 crewmembers of a U.S. Navy ship. METHODS: Retrospective analysis of a survey to include questions about demographics, caffeine consumption, sleep adequacy, the Epworth Sleepiness Scale (ESS), and the Fatigue Severity Scale (FSS). RESULTS: ESS scores (8.41 +/- 4.66) indicated that 32% of the participants had excessive daytime sleepiness (ESS score > 10), while approximately 7% had an ESS score of 16 or more. FSS scores (average FSS = 3.01 +/- 1.37) indicated that 28% of the participants had elevated fatigue (FSS score >= 4). Even though ESS and FSS scores were correlated (r = 0.39), their association explained only 15% of the variability observed. In terms of behavioral and lifestyle patterns, crewmembers with elevated fatigue (FSS >= 4) reported getting less exercise than those reporting less fatigue. Individuals with excessive sleepiness (ESS > 10) reported higher caffeine consumption. Crewmembers with elevated fatigue and comorbid sleepiness (FSS >= 4 and ESS > 10) reported receiving less sleep than other crew members. CONCLUSIONS: These results suggest that subjective fatigue and subjective sleepiness, as measured by the FSS and ESS scales, are distinct constructs and both are consequences of working at sea. The scores on the two scales correlate differentially with behavioral and lifestyle patterns of the crewmembers. PMID- 27662512 TI - Asymmetric zygote division: A mystery starting point of embryogenesis. AB - In angiosperm, asymmetric zygote division is critical for embryogenesis. The molecular mechanism underlying this process has gained a great attention recently. Some players involve in the control of both accurate position and correct orientation of zygote division plane have been found, which provide useful clues for the extensive investigations. It is getting clear that both internal and external factors are involved in this complex regulatory mechanism and the asymmetric zygote division seems with great impact in cell fate determination and embryo pattern formation. PMID- 27662513 TI - Manipulating adenoviral vector ion-exchange chromatography: Hexon versus fiber. AB - The serotype specificity of adenovirus ion-exchange chromatography has previously been studied using standard particle-based columns, and the hexon protein has been reported to determine retention time. In this study, we have submitted Adenovirus type 5 recombinants to anion-exchange chromatography using methacrylate monolithic supports. Our experiments with hexon-modified adenoviral vectors show more precisely that the retention time is affected by the substitution of amino acids in hypervariable region 5, which lies within the hexon DE1 loop. By exploring the recombinants modified in the fiber protein, we have proven the previously predicted chromatographic potential of this surface constituent. Modifications that preserve the net charge of the hexon protein, or those that cause only a small charge difference in the fiber protein, in addition to shortening the fiber shaft, did not change the chromatographic behavior of the adenovirus particles. However, modifications that include the deletion of just two negatively charged amino acids in the hexon protein, or the introduction of a heterologous fiber protein, derived from another serotype, revealed recognizable changes in anion-exchange chromatography. This could be useful in facilitating chromatography-approach purification by creating targeted capsid modifications, thereby shifting adenovirus particles away from particular interfering substances present in the crude lysate. PMID- 27662514 TI - Role of Cyclic Nucleotide Phosphodiesterases During Meiotic Resumption From Diplotene Arrest in Mammalian Oocytes. AB - Cyclic nucleotide phosphodiesterases (PDEs) are group of enzymes that hydrolyze cyclic nucleotides in wide variety of cell types including encircling granulosa cells as well as associated oocytes. One group of PDEs are located in encircling granulosa cells and another group get expressed in the oocyte, while few other PDEs are expressed in both compartments. The PDE1A, PDE4D, PDE5A, PDE8A, and PDE8B are granulosa cell specific PDEs that hydrolyze adenosine 3',5'-cyclic monophosphate (cAMP) as well as guanosine 3',5'-cyclic monophosphate (cGMP) with different affinities. PDE3A, PDE8A as well as PDE9A are expressed in oocyte and specifically responsible for the cyclic nucleotide hydrolysis in the oocyte itself. Few other PDEs such as PDE7B, PDE10A, and PDE11A are either detected in granulosa cells or oocytes. Activation of these PDEs either in encircling granulosa cells or in oocyte directly or indirectly reduces intraoocyte cAMP level. Reduction of intraoocyte cAMP level modulates phosphorylation status of cyclin-dependent kinase 1 (Cdk1) and triggers cyclin B1 degradation that destabilizes maturation promoting factor (MPF) and/or increases Cdk1 activity. The destabilized MPF and/or increased Cdk1 activity leads to resumption of meiosis, which initiates the achievement of meiotic competency in preovulatory follicles of several mammalian species. Use of specific PDEs inhibitors block cyclic nucleotides hydrolysis that results in increase of intraoocyte cyclic nucleotides level, which leads to maintenance of meiotic arrest at diplotene stage in vivo as well as in vitro. Thus, cyclic nucleotide PDEs play important role in the achievement of meiotic competency by reducing intraoocyte cyclic nucleotides level in mammalian oocytes. J. Cell. Biochem. 118: 446-452, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662516 TI - Implant Rehabilitation Planning Protocol for the Edentulous Patient According to Denture Space, Lip Support, and Smile Line. AB - Rehabilitation with implants is a challenge. Having previous evaluation criteria is key to establishing the best treatment for the patient. In addition to clinical and radiological aspects, the prosthetic parameters must be taken into account in the initial workup, since they allow discrimination between fixed and removable rehabilitation. We present a study protocol that analyzes three basic prosthetic aspects. First, denture space defines the need to replace teeth, tissue, or both. Second, lip support focuses on whether or not to include a flange. Third, the smile line warns of potential risks in esthetic rehabilitation. Combining these parameters allows us to make a decision as to the most suitable type of prosthesis. The proposed protocol is useful for assessing the prosthetic parameters that influence decision making as to the best-suited type of restoration. From this point of view, we think it is appropriate for the initial approach to the patient. In any case, other considerations of study may amend the proposal. PMID- 27662515 TI - The Role of Calcium-Sensing Receptors in Endothelin-1-Dependent Effects on Adult Rat Ventricular Cardiomyocytes: Possible Contribution to Adaptive Myocardial Hypertrophy. AB - Nitric oxide (NO)-deficiency as it occurs during endothelial dysfunction activates the endothelin-1 (ET-1) system and increases the expression of receptor activity modifying protein (RAMP)-1 that acts as a chaperon for calcium-sensing receptors (CaR) that have recently been identified to improve cardiac function. Here, we hypothesized that ET-1 increases the cardiac expression of CaR and thereby induces an adaptive type of hypertrophy. Expressions of RAMP-1, endothelin receptors, and CaR were analyzed by RT-PCR in left ventricular tissues of L-NAME-treated rats. Effects of ET-1 on CaR expression and cell function (load free cell shortening) were analyzed in adult rat ventricular cardiomyocytes. siRNA directed against CaR and RAMP-1 was used to investigate a causal relationship. PD142893 and BQ788 were used to dissect the contribution of ETB1 , ETB2 , and ETA receptors. Non-specific NO synthase inhibition with L-Nitro arginine methyl ester (L-NAME) caused a cardiac upregulation of ETB receptors and CaR suggesting a paracrine effect of ET-1 on cardiomyocytes. Indeed, ET-1 induced the expression of CaR in cultured cardiomyocytes. Under these conditions, cardiomyocytes increased cell size (hypertrophy) but maintained normal function. Inhibition of ETA and ETB1 receptors led to ET-1-dependent reduction in cell shortening and attenuated up-regulation of CaR. Down-regulation of RAMP-1 reduced CaR responsiveness. In conclusion, ET-1 causes an adaptive type of hypertrophy by up-regulation of CaR in cardiomyocytes via ETA and/or ETB1 receptors. J. Cell. Physiol. 232: 2508-2518, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662517 TI - Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats. AB - Drug interactions are one of the commonest causes of side effects, particularly in long-term therapy. The aim of the current study was to investigate the possible effects of metoprolol on the pharmacokinetics of metformin in rats and to clarify the mechanism of drug interaction. In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determined by HPLC. Western blotting and real time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7-day repeated administration, the plasma concentrations of metformin in the co-administration group were significantly decreased compared with that in the metformin group. However, the parameter V/F of metformin in the co-administration group was markedly increased compared with that in the metformin group. The hepatic, renal and muscular Kp of metformin were markedly elevated after co-administration with metoprolol. Consistently, metformin uptake in rat kidney slices was significantly induced by metoprolol. In addition, multiple administrations of metoprolol significantly reduced the expression of rMATE1 in rat kidney as well as the urinary excretion of metformin. Importantly, after long-term administration, lactic acid and uric acid levels in the co-administration group were increased by 25% and 26%, respectively, compared with that in the metformin group. These results indicate that metoprolol can decrease the plasma concentration of metformin via the induction of hepatic, renal and muscular uptake, and long-term co-administration of metformin and metoprolol can cause elevated lactic acid and uric acid levels. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27662518 TI - Achieving Pure Deep-Blue Electroluminescence with CIE y<=0.06 via a Rational Design Approach for Highly Efficient Non-Doped Solution-Processed Organic Light Emitting Diodes. AB - Deep-blue fluorescent emitters with Commission Internationale de l'Eclairage (CIE) y<=0.06 are urgently needed for high-density storage, full-color displays and solid-state lighting. However, developing such emitters with high color purity and efficiency in solution-processable non-doped organic light-emitting diodes (OLEDs) remains an important challenge. Here, we present the synthesis of two new deep-blue fluorescent emitters (AFpTPI and AFmTPI) based on 10-(9,9 diethyl-9H-fluoren-2-yl)-9,9-dimethyl-9,10-dihydroacridine as a core and 1,3- and/or 1,4-phenylene-linked triphenylimidazole (TPI) analogues for non-doped solution-processable OLEDs. Their thermal, photophysical, electrochemical, and device characteristics are explored, and also strongly supported by density functional theory (DFT) study. AFpTPI and AFmTPI exhibit excellent thermal stability (~450 degrees C) with high glass transition temperatures (Tg ; 141-152 degrees C) and deep-blue emission with high quantum yields. Specifically, the solution-processed non-doped device with AFpTPI as an emitter exhibits a maximum external quantum efficiency (EQE) of 4.56 % with CIE coordinates of (0.15, 0.06), which exactly matches the European Broadcasting Union (EBU) blue standard. In addition, AFmTPI also displays good efficiency and better color purity (EQE: 3.37 %; CIE (0.15, 0.05)). To the best of our knowledge, the present work is the first report on non-doped solution-processable OLEDs with efficiency close to 5 % and CIE y<=0.06. PMID- 27662519 TI - Relating fitness to long-term environmental variations in natura. AB - Quantifying links between ecological processes and adaptation dynamics in natura remains a crucial challenge. Many studies have documented the strength, form and direction of selection, and its variations in space and time, but only a few managed to link these variations to their proximal causes. This step is, however, crucial, if we are to understand how the variation in selective pressure affects adaptive allele dynamics in natural settings. We used data from a long-term survey (about 30 years) monitoring the adaptation to insecticides of Culex pipiens mosquitoes in Montpellier area (France), focusing on three resistance alleles of the Ester locus. We used a population genetics model taking temporal and spatial variations in selective pressure into account, to assess the quantitative relationships between variations in the proximal agent of selection (amounts of insecticide sprayed) and the fitness of resistance alleles. The response to variations in selective pressure was fast, and the alleles displayed different fitness-to-environment relationships: the analyses revealed that even slight changes in insecticide doses could induce changes in the strength and direction of selection, thus changing the fitness ranking of the adaptive alleles. They also revealed that selective pressures other than the insecticides used for mosquito control affected the resistance allele dynamics. These fitness to-environment relationships, fast responses and continuous evolution limit our ability to predict the outcome of adaptive allele dynamics in a changing environment, but they clearly contribute to the maintenance of polymorphism in natural populations. Our study also emphasizes the necessity of long-term surveys in evolutionary ecology. PMID- 27662520 TI - Identification of 11p14.1-p15.3 deletion probably associated with short stature, relative macrocephaly, and delayed closure of the fontanelles. AB - We herein report a de novo hemizygous 9.2-Mb interstitial deletion of chromosome 11p14.1-15.3 in a 3-year-old Japanese girl with short stature, relative macrocephaly, and delayed closure of cranial fontanelles and sutures. She did not show either any motor or mental development delay. This deletion involves 25 genes including NELL1. The loss of the Nell1 function leads to skeletal defects in the cranial vault and vertebral column, and overexpression of Nell1 causes craniosynostosis in mice. These results imply that short stature and an abnormality of membranous ossification could be explained by haploinsufficiency of NELL1 on 11p14.1-p15.3. Further studies are needed to clarify the phenotype in patients with an 11p14.1-15.3 deletion and the pathogenesis of NELL1. (c) 2016 Wiley Periodicals, Inc. PMID- 27662521 TI - Patterns of antiplatelet drug use after a first myocardial infarction during a 10 year period. AB - AIMS: The aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence. METHODS: The present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System. Antiplatelet drug users were classified as persistent users (gap between prescriptions <=90 days), nonpersistent users (>90-day gap and no refills), and restarters (a new prescription after a >90-day gap). The association between potential determinants and antiplatelet nonpersistence was analysed using Cox regression. RESULTS: The proportions of persistent users decreased from 84.0% at the 1-year follow-up to 32.8% at 10 years for any antiplatelet drug, and 77.3% to 27.5% for aspirin; and 39.0% to 6.4% for clopidogrel at 6 years. Most nonpersistent users restarted antiplatelet drugs later, leading to 89.3% overall antiplatelet drug users at 10 years after MI. Diabetes (hazard ratio [HR] 0.44; 0.32-0.60), hypertension (HR 0.77; 0.60-0.99), hypercholesterolaemia (HR 0.49; 0.39-0.62) and more recent MI diagnosis period (2003-2007: HR 0.69, 0.61-0.79; 2008-2010: HR 0.38, 0.19-0.77, compared to <= 2002 period) lowered the risk of antiplatelet nonpersistence, while vitamin K antagonist (VKA) comedication (HR 18.97; 16.91-21.28) increased this risk. CONCLUSIONS: A large proportion of patients with a first MI still used antiplatelet drugs after 10 years. The frequent discontinuations during this time frame are expected to reduce the effectiveness of antiplatelet drugs as secondary prevention of cardiovascular diseases. Diabetes, hypertension, hypercholesterolaemia, VKA comedication and MI diagnosis period were determinants of antiplatelet nonpersistence. PMID- 27662522 TI - Dermal fillers: pathophysiology, prevention and treatment of complications. AB - Dermal fillers are increasingly used for soft tissue augmentation of the face and hands. The widespread use of dermal fillers for rejuvenation has led to a rise in reports of associated complications. Although the majority of complications are mild and transient, serious and long-lasting complications have been observed. This article discusses the key complications including pigmentary changes, hypersensitivity reactions, infections, nodule formation, granulomatous reactions, vascular occlusion and migration of filler material. A thorough literature review was performed in addition to the combined extensive authors' (GP and FA) experience. Complications from fillers are increasingly being recognized and highlighted in the literature partly reflecting the growth in the market. This article provides a comprehensive overview of the filler complications with mechanisms of prevention and treatment per complication. A thorough understanding of the preventative and management strategies for the associated dermal filler complications will help the physician to prepare the patient well, and deal with complications that may arise effectively. PMID- 27662523 TI - Global population genetic dynamics of a highly migratory, apex predator shark. AB - Knowledge of genetic connectivity dynamics in the world's large-bodied, highly migratory, apex predator sharks across their global ranges is limited. One such species, the tiger shark (Galeocerdo cuvier), occurs worldwide in warm temperate and tropical waters, uses remarkably diverse habitats (nearshore to pelagic) and possesses a generalist diet that can structure marine ecosystems through top-down processes. We investigated the phylogeography and the global population structure of this exploited, phylogenetically enigmatic shark by using 10 nuclear microsatellites (n = 380) and sequences from the mitochondrial control region (CR, n = 340) and cytochrome oxidase I gene (n = 100). All three marker classes showed the genetic differentiation between tiger sharks from the western Atlantic and Indo-Pacific ocean basins (microsatellite FST > 0.129; CR PhiST > 0.497), the presence of North vs. southwestern Atlantic differentiation and the isolation of tiger sharks sampled from Hawaii from other surveyed locations. Furthermore, mitochondrial DNA revealed high levels of intraocean basin matrilineal population structure, suggesting female philopatry and sex-biased gene flow. Coalescent- and genetic distance-based estimates of divergence from CR sequences were largely congruent (dcorr = 0.0015-0.0050), indicating a separation of Indo-Pacific and western Atlantic tiger sharks <1 million years ago. Mitochondrial haplotype relationships suggested that the western South Atlantic Ocean was likely a historical connection for interocean basin linkages via the dispersal around South Africa. Together, the results reveal unexpectedly high levels of population structure in a highly migratory, behaviourally generalist, cosmopolitan ocean predator, calling for management and conservation on smaller-than-anticipated spatial scales. PMID- 27662524 TI - Development of a Suicidal Ideation Detection Tool for Primary Healthcare Settings: Using Open Access Online Psychosocial Data. AB - BACKGROUND: Suicidal patients often visit healthcare professionals in their last month before suicide, but medical practitioners are unlikely to raise the issue of suicide with patients because of time constraints and uncertainty regarding an appropriate approach. INTRODUCTION: A brief tool called the e-PASS Suicidal Ideation Detector (eSID) was developed for medical practitioners to help detect the presence of suicidal ideation (SI) in their clients. If SI is detected, the system alerts medical practitioners to address this issue with a client. The eSID tool was developed due to the absence of an easy-to-use, evidence-based SI detection tool for general practice. MATERIAL AND METHODS: The tool was developed using binary logistic regression analyses of data provided by clients accessing an online psychological assessment function. Ten primary healthcare professionals provided advice regarding the use of the tool. RESULTS: The analysis identified eleven factors in addition to the Kessler-6 for inclusion in the model used to predict the probability of recent SI. The model performed well across gender and age groups 18-64 (AUR 0.834, 95% CI 0.828-0.841, N = 16,703). Healthcare professionals were interviewed; they recommended that the tool be incorporated into existing medical software systems and that additional resources be supplied, tailored to the level of risk identified. CONCLUSION: The eSID is expected to trigger risk assessments by healthcare professionals when this is necessary. Initial reactions of healthcare professionals to the tool were favorable, but further testing and in situ development are required. PMID- 27662525 TI - Electronic properties of an exciton in CdTe/CdSe/CdTe/CdSe type-II nano heterostructure. AB - In this study, we have carried out a detailed theoretical investigation on the binding energy of an exciton in type-II CdTe/CdSe core/shell/well/shell (CSWS) nanocrystal quantum dot (NCQD) in the strong confinement region. The calculations are based on the effective mass approximation, and the coulombic interaction between electron and hole is introduced using Hartree approximation. With these theoretical basis, the coupled Poisson-Schrodinger equations are solved in a self consistent iterative manner. In strong confinement regime, the binding energy variation with core radius in type-II NCQD shows a peak. And this peak widens for larger well width and inner shell thickness. Our study suggests that, this anomalous behavior of exciton binding energy is due to an effect called 'positional flip of exciton', caused by the faster tunneling of hole to the inner layer in comparison with electron. Our results can be applied in laser and optoelectronic engineering for designing more efficient optoelectronic devices. PMID- 27662526 TI - Review of Teenlink: A health service for children and adolescents of parents with substance use. AB - AIM: To evaluate Teenlink, a wide-ranging medical and psychological health service addressing the needs of children and adolescents in substance-using families, who are at increased risk of developmental and psychosocial problems. METHODS: Retrospective record review of 124 children, from 92 families seen over a 13 year period. RESULTS: Polysubstance use and mental illness were common amongst parents. Children often presented with emotional and behavioural problems. Teenlink provided parenting skills, individual and family work, medical care, case management, advocacy, collaboration and education with adult drug and alcohol services. CONCLUSIONS: The chronic and complex nature of parental addiction, need for ongoing support and tailored service utilisation, reflected the length of engagement. PMID- 27662527 TI - Atypical psychotic symptoms and Dandy-Walker variant. AB - New-onset psychotic symptoms often respond well to antipsychotic treatment; however, symptoms may be difficult to treat when an underlying brain malformation is present. Here, we present a case of atypical psychotic symptoms in the context of a congenital cerebellar malformation (Dandy-Walker variant). The patient ultimately improved with paliperidone palmitate after multiple antipsychotic medication trials (both oral and one long-acting injectable) were ineffective. Neuroimaging may provide valuable diagnostic and prognostic information in cases of new-onset psychosis with atypical features and treatment resistance, even in the absence of neurologic signs and symptoms. PMID- 27662528 TI - Family Forward: Promoting Family Adaptation Following Pediatric Acquired Brain Injury. AB - This article describes a new and innovative social work intervention, Family Forward, designed to promote early adaptation of the family system after the onset of a child's acquired brain injury. Family Forward is integrated into inpatient rehabilitation services provided to the injured child and recognizes the important role of family in child rehabilitation outcomes and the parallel process of recovery for the child and family following an injury. Family Forward is informed by clinical practice, existing research in family adaptation after pediatric acquired brain injury, the resiliency model of family adjustment and adaptation, and family therapy theories and approaches. PMID- 27662529 TI - Treatment of traumatic brain injury with 17alpha-ethinylestradiol-3-sulfate in a rat model. AB - OBJECTIVE 17alpha-ethynylestradiol-3-sulfate (EE-3-SO4) is a highly water-soluble synthetic estrogen that has an extended half-life (~ 10 hours) over that of naturally occurring estrogen (~ 10 minutes). In this study, EE-3-SO4 was evaluated in a lateral fluid percussion-induced traumatic brain injury (TBI) model in rats. METHODS A total of 9 groups of Sprague-Dawley rats underwent craniectomy. Twenty-four hours later, lateral fluid percussion was applied to 6 groups of animals to induce TBI; the remaining 3 groups served as sham control groups. EE-3-SO4 (1 mg/kg body weight in 0.4 ml/kg body weight) or saline (vehicle control) was injected intravenously 1 hour after TBI; saline was injected in all sham animals. One day after EE-3-SO4/saline injection, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and partial brain oxygen pressure (PbtO2) were measured in Groups 1-3 (2 TBI groups and 1 sham group), and brain edema, diffusion axonal injury, and cerebral glycolysis were assessed in Groups 4-6 using MRI T2 mapping, diffusion tensor imaging (DTI), and FDG-PET imaging, respectively. Four days after dosing, the open-field anxiety of animals was assessed in Groups 7-9 by measuring the duration that each animal spent in the center area of an open chamber during 4 minutes of monitoring. RESULTS EE-3-SO4 significantly lowered ICP while raising CPP and PbtO2, compared with vehicle treatment in TBI-induced animals (p < 0.05). The mean size of cerebral edema of TBI animals treated with EE-3-SO4 was 25 +/- 3 mm3 (mean +/- SE), which was significantly smaller than that of vehicle-treated animals (67 +/- 6 mm3, p < 0.001). Also, EE-3-SO4 treatment significantly increased the fractional anisotropy of the white matter in the ipsilateral side (p = 0.003) and cerebral glycolysis (p = 0.014). The mean duration that EE-3-SO4-treated animals spent in the center area was 12 +/- 2 seconds, which was significantly longer than that of vehicle-treated animals (4 +/- 1 seconds; p = 0.008) but not different from that of sham animals (11 +/- 3 seconds; p > 0.05). CONCLUSIONS These data support the clinical use of EE-3-SO4 for early TBI treatment. PMID- 27662530 TI - Approach selection for intrinsic brainstem pathologies. PMID- 27662531 TI - Effects of transcranial stimulating electrode montages over the head for lower extremity transcranial motor evoked potential monitoring. AB - OBJECTIVE The aim of this study was to determine the most effective electrode montage to elicit lower-extremity transcranial motor evoked potentials (LE-tMEPs) using a minimum stimulation current. METHODS A realistic 3D head model was created from T1-weighted images. Finite element methods were used to visualize the electric field in the brain, which was generated by transcranial electrical stimulation via 4 electrode montage models. The stimulation threshold level of LE tMEPs in 52 patients was also studied in a practical clinical setting to determine the effects of each electrode montage. RESULTS The electric field in the brain radially diffused from the brain surface at a maximum just below the electrodes in the finite element models. The Cz-inion electrode montage generated a centrally distributed high electric field with a current direction longitudinal and parallel to most of the pyramidal tract fibers of the lower extremity. These features seemed to be effective in igniting LE-tMEPs. Threshold level recordings of LE-tMEPs revealed that the Cz-inion electrode montage had a lower threshold on average than the C3-C4 montage, 76.5 +/- 20.6 mA and 86.2 +/- 20.6 mA, respectively (31 patients, t = 4.045, p < 0.001, paired t-test). In 23 (74.2%) of 31 cases, the Cz-inion montage could elicit LE-tMEPs at a lower threshold than C3 C4. CONCLUSIONS The C3-C4 and C1-C2 electrode montages are the standard for tMEP monitoring in neurosurgery, but the Cz-inion montage showed lower thresholds for the generation of LE-tMEPs. The Cz-inion electrode montage should be a good alternative for LE-tMEP monitoring when the C3-C4 has trouble igniting LE-tMEPs. PMID- 27662532 TI - Complication rates, lengths of stay, and readmission rates in "awake" and "asleep" deep brain simulation. AB - OBJECTIVE As the number of deep brain stimulation (DBS) procedures performed under general anesthesia ("asleep" DBS) increases, it is more important to assess the rates of adverse events, inpatient lengths of stay (LOS), and 30-day readmission rates in patients undergoing these procedures compared with those in patients undergoing traditional "awake" DBS without general anesthesia. METHODS All patients in an institutional database who had undergone awake or asleep DBS procedures performed by a single surgeon between August 2011 and August 2014 were reviewed. Adverse events, inpatient LOS, and 30-day readmissions were analyzed. RESULTS A total of 490 electrodes were placed in 284 patients, of whom 126 (44.4%) underwent awake surgery and 158 (55.6%) underwent asleep surgery. The most frequent overall complication for the cohort was postoperative mental status change (13 patients [4.6%]), followed by hemorrhage (4 patients [1.4%]), seizure (4 patients [1.4%]), and hardware-related infection (3 patients [1.1%]). Mean LOS for all 284 patients was 1.19 +/- 1.29 days (awake: 1.06 +/- 0.46 days; asleep: 1.30 +/- 1.67 days; p = 0.08). Overall, the 30-day readmission rate was 1.4% (1 awake patient, 3 asleep patients). There were no significant differences in complications, LOS, and 30-day readmissions between awake and asleep groups. CONCLUSIONS Both awake and asleep DBS can be performed safely with low complication rates. The authors found no significant differences between the 2 procedure groups in adverse events, inpatient LOS, and 30-day readmission rates. PMID- 27662533 TI - Letter to the Editor: Simpson grading system. PMID- 27662534 TI - Early versus late arteriovenous malformation responders after stereotactic radiosurgery: an international multicenter study. AB - OBJECTIVE The goal of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) is complete nidus obliteration, thereby eliminating the risk of future hemorrhage. This outcome can be observed within the first 18 months, although documentation of AVM obliteration can extend to as much as 5 years after SRS is performed. A shorter time to obliteration may impact the frequency and effect of post-SRS complications and latency hemorrhage. The authors' goal in the present study was to determine predictors of early obliteration (18 months or less) following SRS for cerebral AVM. METHODS Eight centers participating in the International Gamma Knife Research Foundation (IGKRF) obtained institutional review board approval to supply de-identified patient data. From a cohort of 2231 patients, a total of 1398 patients had confirmed AVM obliteration. Patients were sorted into early responders (198 patients), defined as those with confirmed nidus obliteration at or prior to 18 months after SRS, and late responders (1200 patients), defined as those with confirmed nidus obliteration more than 18 months after SRS. The median clinical follow-up time was 63.7 months (range 7-324.7 months). RESULTS Outcome parameters including latency interval hemorrhage, mortality, and favorable outcome were not significantly different between the 2 groups. Radiologically demonstrated radiation-induced changes were noted more often in the late responder group (376 patients [31.3%] vs 39 patients [19.7%] for early responders, p = 0.005). Multivariate independent predictors of early obliteration included a margin dose > 24 Gy (p = 0.031), prior surgery (p = 0.002), no prior radiotherapy (p = 0.025), smaller AVM nidus (p = 0.002), deep venous drainage (p = 0.039), and nidus location (p < 0.0001). Basal ganglia, cerebellum, and frontal lobe nidus locations favored early obliteration (p = 0.009). The Virginia Radiosurgery AVM Scale (VRAS) score was significantly different between the 2 responder groups (p = 0.039). The VRAS score was also shown to be predictive of early obliteration on univariate analysis (p = 0.009). For early obliteration, such prognostic ability was not shown for other SRS- and AVM-related grading systems. CONCLUSIONS Early obliteration (<= 18 months post SRS) was more common in patients whose AVMs were smaller, located in the frontal lobe, basal ganglia, or cerebellum, had deep venous drainage, and had received a margin dose > 24 Gy. PMID- 27662535 TI - Predictors of admission and shunt revision during emergency department visits for shunt-treated adult patients with idiopathic intracranial hypertension. AB - OBJECTIVE Factors associated with emergency department admission and/or shunt revision for idiopathic intracranial hypertension (IIH) are unclear. In this study, the associations of several factors with emergency department admission and shunt revision for IIH were explored. METHODS The authors performed a retrospective review of 31 patients (169 total emergency department visits) who presented to the emergency department for IIH-related symptoms between 2003 and 2015. Demographics, comorbidities, symptoms, IIH diagnosis and treatment history, ophthalmological examination, diagnostic lumbar puncture (LP), imaging findings, and data regarding admission and management decisions were collected. Multivariable general linear models regression analysis was performed to assess the predictive factors associated with admission and shunt revision. RESULTS Thirty-one adult patients with a history of shunt placement for IIH visited the emergency department a total of 169 times for IIH-related symptoms, with a median of 3 visits (interquartile range 2-7 visits) per patient. Five patients had more than 10 emergency department visits. Baseline factors associated with admission included male sex (OR 10.47, 95% CI 2.13-51.56; p = 0.004) and performance of an LP (OR 3.10, 95% CI 1.31-7.31; p = 0.01). Contrastingly, older age at presentation (OR 0.94, 95% CI 0.90-0.99; p = 0.01), and a greater number of prior emergency department visits (OR 0.94, 95% CI 0.89-0.99; p = 0.02) were slightly protective against admission. The presence of papilledema (OR 11.62, 95% CI 3.20 42.16; p < 0.001), Caucasian race (OR 40.53, 95% CI 2.49-660.09 p = 0.009), and systemic hypertension (OR 7.73, 95% CI 1.11-53.62; p = 0.03) were independent risk factors for shunt revision. In addition, a greater number of prior emergency department visits (OR 0.86, 95% CI 0.77-0.96; p = 0.009) and older age at presentation (OR 0.93, 95% CI 0.87-0.99; p = 0.02) were slightly protective against shunt revision, while there was suggestive evidence that presence of a programmable shunt (OR 0.23, 95% CI 0.05-1.14; p = 0.07) was a protective factor against shunt revision. Of note, location of the proximal catheter in the ventricle or lumbar subarachnoid space was not significantly associated with admission or shunt revision in the multivariable analyses. CONCLUSIONS The decision to admit a shunt-treated patient from the emergency department for symptoms related to IIH is challenging. Knowledge of factors associated with the need for admission and/or shunt revision is required. In this study, factors such as male sex, younger age at presentation, lower number of prior emergency department visits, and performance of a diagnostic LP were independent predictors of admission. In addition, papilledema was strongly predictive of the need for shunt revision, highlighting the importance of an ophthalmological examination for shunt-treated adults with IIH who present to the emergency department. PMID- 27662536 TI - The application of T2W SPIR-FLAIR in the diagnosis of hip synovitis in patients with spondyloarthritis. AB - OBJECTIVE: To investigate the feasibility and accuracy of T2 weighted spectral pre-saturation inversion recovery combined with fluid-attenuated inversion recovery (T2W SPIR-FLAIR) in the diagnosis of hip synovitis in patients with spondyloarthritis (SpA). METHODS: 10 volunteers underwent a T2W SPIR and 4 T2W SPIR-FLAIR sequence scans with different inversion times (TIs) to determine the optimum TI that could effectively suppress the intra-articular fluid signals. Hip MRI including T2W SPIR-FLAIR and enhanced T1 weighted (T1W) SPIR sequences was performed in 45 patients with SpA and totally 90 hips were evaluated. McNemar's test and Kappa test were used to compare the diagnostic results of synovitis between T2W SPIR-FLAIR and enhanced T1W SPIR. RESULTS: A TI of 2100 ms was selected as the optimum TI. 32 hips from 17 patients exhibited high signal intensity within the articular cavity on both T2W SPIR-FLAIR and enhanced T1W SPIR sequences, while only 3 hips showed high signals within the articular cavity on T2W SPIR-FLAIR. The remaining 55 hips did not show high signals within the articular cavity on both sequences. The T2W SPIR-FLAIR and enhanced T1W SPIR sequences had similar values in the diagnosis of hip synovitis (p = 0.25) and a high degree of diagnostic consistency (Kappa = 0.929). CONCLUSION: T2W SPIR-FLAIR can effectively suppress the intra-articular fluid signals, while retaining the signals of thickened synovial membranes and can be used for the diagnosis of hip synovitis in patients with SpA. Advances in knowledge: The enhanced T1W SPIR is a classic sequence for synovitis diagnosis, but it requires the injection of contrast agents. The T2W SPIR-FLAIR and enhanced T1W SPIR sequences had similar values in the diagnosis of hip synovitis (p = 0.25) and a high degree of diagnostic consistency (Kappa = 0.929). PMID- 27662537 TI - The application of mass spectrometry to leukemia drug discovery. PMID- 27662538 TI - Traumatic brain injury: The first 15 milliseconds. AB - OBJECTIVE: The physical events of the first 15 milliseconds of a traumatic brain injury are reviewed from computer simulations using finite element calculations and applied to observed pathology. METHODS: The impact creates two shock waves; one through the brain, another through the skull, both injure the brain separately. Two accelerations, anteroposterior and rotary, distort or stretch the brain, because of inertia. The two shockwaves are reflected many times within in the brain, from boundaries where the density or elasticity changes. RESULTS: Overlapping waves form powerful positive or negative pressure nodes. Negative waves are more damaging to neurones and blood vessels, so a random pattern of scattered neural and capillary necroses develop all over the brain. The skull shockwave expands the skull opposite the blow, so creating a damaging negative pressure injury to the brain, contre coup contusion. Acceleration (or deceleration) follows impact, beginning later and lasting longer. Inertia strains the tissue, where the brain is free to move, inflicting characteristic white matter injuries. CONCLUSIONS: In the antero-posterior plane, acceleration and inertia stretch and tear long tracts to the spine and blood vessels running from the brain to the dura. Rotatory accelerations stress the inter-hemispheric connections of the brain, especially the corpus callosum, between the hemispheres. PMID- 27662539 TI - Violent Video Games Exposed: A Blow by Blow Account of Senseless Violence in Games. AB - Violent video game (VVG) use has repeatedly been found to be associated with hostile expectations about others, desensitization to violence, decreased empathy and prosocial behavior, and aggressive thoughts and behaviors. Although these research findings have been widely publicized, VVGs remain the most extensively played games and represent a multi-billion dollar industry. Although VVGs are typically rated "mature," indicating they are not suitable for youths, they are often purchased for youths. This may be in part because there is currently no system available to consumers that thoroughly describes the content of video games, and much of the public is unaware of the types of violence that characterize game play. The purpose of this paper is to describe the violent content of some of the top VVGs, based on sales. For the purposes of this issue, acts of senseless, unprovoked violence will be described in detail. PMID- 27662540 TI - Shoulder Dystocia: Incidence and Risk Factors. AB - Shoulder dystocia complicates ~1% of vaginal births. Although fetal macrosomia and maternal diabetes are risk factors for shoulder dystocia, for the most part its occurrence remains largely unpredictable and unpreventable. PMID- 27662541 TI - Recurrent Shoulder Dystocia: Risk Factors and Counseling. AB - A prior history of delivery complicated by shoulder dystocia confers a 6-fold to nearly 30-fold increased risk of shoulder dystocia recurrence in a subsequent vaginal delivery, with most reported rates between 12% and 17%. Whereas prevention of shoulder dystocia in the general population is neither feasible nor cost-effective, directing intervention efforts at the particular subgroup of women with a prior history of shoulder dystocia has merit. Potentially modifiable risk factors and individualized management strategies that may reduce shoulder dystocia recurrence and its associated significant morbidities are reviewed. PMID- 27662542 TI - Maternal Endogenous Forces and Shoulder Dystocia. AB - Childbirth is a complicated biomechanical process that many take for granted. However, the delivery forces generated by a mother (uterine contractions and maternal pushing) are strong and have a significant effect on the body and tissues of the fetus, especially during the second stage of labor. Although most infants are born without negative, force-related outcomes, in some infants the normal forces of labor cause an injury that can have either temporary or permanent sequelae. The biomechanical situation is further complicated when an infant's shoulder impacts the maternal pelvis, which provides increased resistance and creates added stresses within the neonatal body and tissues. PMID- 27662543 TI - Shoulder Dystocia: Quality, Safety, and Risk Management Considerations. AB - Shoulder dystocia is a term that evokes terror and fear among many physicians, midwives, and health care providers as they recollect at least 1 episode of shoulder dystocia in their careers. Shoulder dystocia can result in significant maternal and neonatal complications. Because shoulder dystocia is an urgent, unanticipated, and uncommon event with potentially catastrophic consequences, all practitioners and health care teams must be well-trained to manage this obstetric emergency. Preparation for shoulder dystocia in a systematic way, through standardization of process, practicing team-training and communication, along with technical skills, through simulation education and ongoing quality improvement initiatives will result in improved outcomes. PMID- 27662544 TI - Criminal justice involvement history is associated with better HIV care continuum metrics among a population-based sample of young black MSM. AB - OBJECTIVE: To examine how history of criminal justice involvement (CJI) is related to HIV care continuum metrics among young black MSM 16-29 years of age. DESIGN: Population-based survey. METHODS: From 2013 to 2014, a representative sample of young black MSM was generated using respondent-driven sampling (RDS) in Chicago (n = 618). HIV antibody/antigen and RNA testing were performed using dry blood spots. Factors assessed in the care continuum included HIV testing, HIV diagnosis, linkage to care within 6 months, retention in care, adherence to antiretrovirals, and viral suppression. RDS-weighted regression models examined the associations between history of CJI, including frequency of CJI and durations of stay and each of the continuum metrics. RESULTS: A final analytic sample of 618 participants was generated through RDS chains of up to 13 waves in length and with a mean of 2.1 recruits per participant. At enrollment, 40.8% had prior history of CJI and 34.6% were HIV seropositive. Of persons reporting HIV seropositive status, 58.4% were linked to care, 40.2% were retained in care, 32.2% were adherent to antiretrovirals, and 24.3% were virally suppressed. Any CJI history was associated with the overall care continuum (adjusted odds ratio = 2.35; 95% confidence interval 1.13-4.88) and was most associated with increased retention in care [adjusted odds ratio = 3.72 (1.77-7.84)]. Having one CJI experience and detention for only 1 day was associated with better retention in care compared with no or more frequent CJI. CONCLUSION: Those with a previous history of CJI were more successful in achieving most HIV care continuum metrics. Frequent and cycling CJI, however, was detrimental to HIV care. PMID- 27662545 TI - Long-term body composition changes in antiretroviral-treated HIV-infected individuals. AB - OBJECTIVE: Body composition impacts physical function and mortality. We compared long-term body composition changes after antiretroviral therapy (ART) initiation in HIV-infected individuals to that in HIV-uninfected controls. DESIGN: Prospective observational study. METHODS: We performed dual-energy x-ray absorptiometry (DXA) approximately 7.5 years after initial DXA in available HIV infected individuals who received DXAs during the randomized treatment trial AIDS Clinical Trials Group A5202. For controls, we used DXA results from HIV uninfected participants in the Boston Area Community Health/Bone and Women's Interagency HIV Study cohorts. Repeated measures analyses compared adjusted body composition changes between HIV-infected and HIV-uninfected individuals. Multivariable analyses evaluated factors associated with body composition change in HIV-infected individuals. RESULTS: We obtained DXA results in 97 HIV-infected and 614 HIV-uninfected participants. Compared with controls, HIV-infected individuals had greater adjusted lean mass and total, trunk, and limb fat gain during the first 96 weeks of ART. Subsequently, HIV-infected individuals lost lean mass compared with controls. Total, trunk, and limb fat gains after 96 weeks of ART slowed in HIV-infected individuals but remained greater than in controls. Lower CD4 T-cell count was associated with lean mass and fat gain during the initial 96 weeks of ART, but subsequently no HIV-related characteristic was associated with body composition change. CONCLUSION: Consistent with a 'return to health effect', HIV-infected individuals, especially those with lower baseline CD4 T-cell counts, gained more lean mass and fat during the first 96 weeks of ART than HIV-uninfected individuals. Continued fat gain and lean mass loss after 96 weeks may predispose HIV-infected individuals to obesity-related diseases and physical function impairment. PMID- 27662547 TI - Initiation of antiretroviral therapy based on the 2015 WHO guidelines. AB - OBJECTIVE: In 2015, the WHO recommended initiation of antiretroviral therapy (ART) in all HIV-positive patients regardless of CD4 cell count. We evaluated the cost-effectiveness of immediate versus deferred ART initiation among patients with CD4 cell counts exceeding 500cells/MUl in four resource-limited countries (South Africa, Nigeria, Uganda, and India). DESIGN: A 5-year Markov model with annual cycles, including patients at CD4 cell counts more than 500 cells/MUl initiating ART or deferring therapy until historic ART initiation criteria of CD4 cell counts more than 350 cells/MUl were met. METHODS: The incidence of opportunistic infections, malignancies, cardiovascular disease, unscheduled hospitalizations, and death, were informed by the START trial results. Risk of HIV transmission was obtained from a systematic review. Disability weights were based on published literature. Cost inputs were inflated to 2014 US dollars and based on local sources. Results were expressed in cost per disability-adjusted life years averted and measured against WHO cost-effectiveness thresholds. RESULTS: Immediate initiation of ART is associated with a cost per disability adjusted life years averted of -$317 [95% confidence interval (CI): -$796-$817] in South Africa; -$507 (95% CI: -$765-$837) in Nigeria; -$136 (-$382-$459) in Uganda; and -$78 (-$256-$374) in India. The results are largely driven by the impact of ART on reducing the risk of new HIV transmissions. CONCLUSIONS: In HIV positive patients with CD4 counts above 500 cells/MUl in the four studied countries, immediate initiation of ART versus deferred therapy until historic eligibility criteria are met is cost-effective and likely even cost-saving over time. PMID- 27662546 TI - Chronic lung disease in HIV-infected children established on antiretroviral therapy. AB - OBJECTIVE: Respiratory disease is a major cause of morbidity and mortality in HIV infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group. DESIGN: A cross-sectional study in Zimbabwe of HIV-infected children aged 6-16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area. METHODS: Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4 cell count, HIV viral load and sputum culture for tuberculosis were performed. RESULTS: A total of 202 HIV infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8-7.5) and 6.1 (interquartile range 3.6-8.4) years, respectively. Median CD4 cell count was 726 cells/MUl, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis. CONCLUSION: In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required. PMID- 27662548 TI - In-utero exposure to nelfinavir-ethyl methyl sulfone. AB - Ethyl methyl sulfone contained in nelfinavir between 2007 and 2008 accidentally exposed embryos and fetuses to a powerful mutagen. We report data for 101 HIV uninfected children exposed in utero included in the French prospective national cohort. The incidence of malformation was similar to that in the cohort as a whole with different drug exposures; no children had developed cancer after 9 years of follow-up. PMID- 27662549 TI - Fixed-dose combination emtricitabine/tenofovir/efavirenz initiated during acute HIV infection; 96-week efficacy and durability. AB - BACKGROUND: Updated guidelines recommend immediate antiretroviral treatment (ART) during acute HIV infection (AHI), but efficacy data on regimens during AHI are limited. METHODS: We provide final data on a prospective, single-arm 96-week open label study of once-daily emtricitabine/tenofovir/efavirenz initiated during AHI. The primary endpoint was the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression, retention, and CD8 cell activation through week 96 in relation to baseline characteristics. RESULTS: Between January 2005 and December 2011, 92 AHI participants enrolled. Most participants (78%) were men who have sex with men (MSM), and 42% were young MSM (18-25 years of age). Two participants withdrew leaving 90 patients for analysis. Eighty-one (90%) remained on therapy and achieved viral suppression to less than 200 copies/ml by week 24, and 71 (79%) to less than 50 copies/ml at week 48. The median time from ART initiation to suppression less than 200 copies/ml was 65 days (range 7-523) and to less than 50 copies/ml was 105 days (range 14-523). The frequency of immune activation declined from a median of 67% to 16% through week 96. Retention on study was maintained in 92% of participants at week 48 and in 83% through week 96. Among 75 participants retained through week 96, 92% were suppressed to less than 50 copies/ml. Among 39 young MSM, 79% completed a week 96 visit and 67% were suppressed at week 96. CONCLUSION: ART during AHI resulted in rapid and sustained viral suppression with high rates of retention in care and on ART in this cohort including a large proportion of young MSM. PMID- 27662550 TI - Concurrency and HIV transmission network characteristics among MSM with recent HIV infection. AB - OBJECTIVE: Sexual partner concurrency is common among MSM and may increase the probability of HIV transmission during recent (acute or early) infection. We examined the relationship between concurrency and HIV transmission network characteristics (proxies for HIV transmission) among MSM with recent HIV infection. DESIGN: Observational study integrating behavioral, clinical, and molecular epidemiology. METHODS: We inferred a partial HIV transmission network using 986 HIV-1 pol sequences obtained from HIV-infected individuals in San Diego, California (1996-2015). We further analyzed data from 285 recently HIV infected MSM in the network who provided information on up to three sexual partners in the past 3 months, including the timing of intercourse with each partner. Concurrency was defined as sexual partners overlapping in time. Logistic and negative binomial regressions were used to investigate the link between concurrency and HIV transmission network characteristics (i.e. clustering and degree or number of connections to others in the network) among these MSM. RESULTS: Of recently HIV-infected MSM (n = 285), 54% reported concurrent partnerships and 54% were connected by at least one putative transmission link to others (i.e. clustered) in the network (median degree = 1.0; interquartile range: 0.0-3.0). Concurrency was positively associated with HIV transmission network clustering (adjusted odds ratio = 1.83, 95% confidence interval: 1.08, 3.10) and degree (adjusted incidence rate ratio = 1.48, 95% confidence interval: 1.02, 2.15). CONCLUSION: Our findings provide empirical evidence consistent with the hypothesis that concurrency facilitates HIV transmission during recent infection. Interventions to mitigate the impact of concurrency on HIV transmission may help curb the HIV epidemic among MSM. PMID- 27662555 TI - Buy one, get one free? Benefits of certain antiretrovirals against malaria. PMID- 27662551 TI - Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa. AB - OBJECTIVE: Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the WHO recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants. DESIGN/METHODS: We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in four African countries. Ninety three percent of HIV+ infants were receiving antiretroviral therapy prior to vaccination. Participants were followed for safety. Immune responses were measured 14 days after three doses of RV5, including serum antirotavirus neutralizing and IgA antibodies, IgA antibody in stool, and antirotavirus memory B and T-cell FluoroSpot. Shedding of RV5 in stool was monitored. RESULTS: A total of 76 HIV+ and 126 HEU infants were enrolled from 2009 to 2013. No significant differences were found in adverse event rates, including grade 3 events, between RV5 and placebo recipients, for either HIV+ or HEU infants. The proportion of antirotavirus IgA responders (at least three-fold increase from baseline) after RV5 administration was 81% in both HIV+ and HEU infants, which was approximately 2.5-fold higher than in placebo recipients (P < 0.001). Neutralizing antibody responses to three of five serotypes were significantly higher after RV5 regardless of HIV status, and those of HIV+ infants were equal or greater than responses of HEU infants to all five serotypes. Only one HIV+ RV5 recipient had RV5 isolated from stool. CONCLUSION: RV5 was immunogenic in both HIV+ and HEU infants and no safety signals were observed. PMID- 27662556 TI - Reduced bacterial skin infections in HIV-infected African children randomized to long-term cotrimoxazole prophylaxis. AB - OBJECTIVE: To evaluate whether cotrimoxazole prophylaxis prevents common skin conditions in HIV-infected children. DESIGN: Open-label randomized controlled trial of continuing versus stopping daily cotrimoxazole (post-hoc analysis). SETTING: Three sites in Uganda and one in Zimbabwe. PARTICIPANTS: A total of 758 children aged more than 3 years receiving antiretroviral therapy (ART) for more than 96 weeks in the ARROW trial were randomized to stop (n = 382) or continue (n = 376) cotrimoxazole after median (interquartile range) 2.1(1.8, 2.2) years on ART. INTERVENTION: Continuing versus stopping daily cotrimoxazole. MAIN OUTCOME MEASURES: Nurses screened for signs/symptoms at 6-week visits. This was a secondary analysis of ARROW trial data, with skin complaints categorized blind to randomization as bacterial, fungal, or viral infections; dermatitis; pruritic papular eruptions (PPEs); or others (blisters, desquamation, ulcers, and urticaria). Proportions ever reporting each skin complaint were compared across randomized groups using logistic regression. RESULTS: At randomization, median (interquartile range) age was 7 (4, 11) years and CD4 was 33% (26, 39); 73% had WHO stage 3/4 disease. Fewer children continuing cotrimoxazole reported bacterial skin infections over median 2 years follow-up (15 versus 33%, respectively; P < 0.001), with similar trends for PPE (P = 0.06) and other skin complaints (P = 0.11), but not for fungal (P = 0.45) or viral (P = 0.23) infections or dermatitis (P = 1.0). Bacterial skin infections were also reported at significantly fewer clinic visits (1.2 versus 3.0%, P < 0.001). Independent of cotrimoxazole, bacterial skin infections were more common in children aged 6-8 years, with current CD4 cell count less than 500 cells/MUl, WHO stage 3/4, less time on ART, and lower socio-economic status. CONCLUSION: Long-term cotrimoxazole prophylaxis reduces common skin complaints, highlighting an additional benefit for long-term prophylaxis in sub-Saharan Africa. PMID- 27662559 TI - Allotransplantation of the Eye: Context and Possible Considerations for a Future Guided by Anatomy. PMID- 27662558 TI - External Auditory Canal Stenosis After Traumatic Auricular Amputation. AB - BACKGROUND: The auricles are easily injured or amputated in case of head trauma. Inadequate treatment of the external auditory canal (EAC) after auricular injury is often seen and can lead to significant complications of the EAC. CASE REPORT: The authors report 4 cases of auricular injury or amputations. In all patients inadequate first treatment led to stenosis of the EAC. Three patients required recanalization of the EAC because of hearing loss and the risk of further complications. CONCLUSION: Treatment of auricular injury should consist of (pre emptive) packing of the EAC with antibiotic gauzes followed by thorough examination of the EAC to prevent canal stenosis and subsequent complications. PMID- 27662557 TI - Inequalities by educational level in response to combination antiretroviral treatment and survival in HIV-positive men and women in Europe. AB - BACKGROUND: Socioeconomic inequality challenges population-level implementation of health interventions. We investigated differences by educational level in clinical, virological, and immunological responses to combined antiretroviral treatment (cART) in HIV-positive men and women in Collaboration of Observational HIV Epidemiological Research in Europe, a European collaboration. METHODS: Data were pooled from 15 cohorts in eight countries of patients initiating cART in 1996-2013 with data on educational level categorized in UNESCO/ISCED classifications. Kaplan-Meier curves, Cox and piecewise linear mixed models were used. RESULTS: Of 24 069 HIV-positive patients, 9% had not completed primary education, 32% had completed primary, 44% secondary, and 15% tertiary education. Overall, 21% were women, who were overrepresented in lower educational strata. During 132 507 person-years of follow-up, 1081 individuals died; cumulative mortality decreased with higher educational level (P < 0.001). Over 122 765 person-years, new AIDS events or death occurred in 2598 individuals; differences by education were more marked than for death alone (P < 0.001). Virological response was achieved by 67% of patients without completed basic education, 85% with completed primary education, 82% with secondary, and 87% with tertiary (P < 0.001). Patients with higher education had higher CD4 cell count at cART initiation and at each time after cART but rate of CD4 cell count recovery did not differ. Differences in mortality and clinical responses were similar for men and women and were not entirely explained by delayed HIV diagnosis and late cART initiation. CONCLUSION: HIV-positive patients with lower educational level had worse responses to cART and survival in European countries with universal healthcare. To maximize the population impact of cART, Europe needs to decrease the socioeconomic divide. PMID- 27662560 TI - Cerebral Oximetry During CEA: Is It an Ideal Monitor? PMID- 27662561 TI - Global and Cerebral Metabolism and Systemic and Cerebral Oxygenation During and After Intraoperative Seizures in a Patient Undergoing Brain Tumor Surgery. PMID- 27662563 TI - Locally Acquired Eastern Equine Encephalitis Virus Disease, Arkansas, USA. PMID- 27662562 TI - Are myelodysplastic syndromes and acute myeloid leukaemia occurring during the course of lymphoma always therapy related? PMID- 27662564 TI - Hematocrit Levels, Blood Testing, and Blood Transfusion in Infants After Heart Surgery. AB - OBJECTIVE: To determine whether judicious blood testing impacts timing or amount of packed RBC transfusions in infants after heart surgery. DESIGN: A retrospective study comparing before and after initiation of a quality improvement process. SETTING: A university-affiliated cardiac ICU at a tertiary care children's hospital. PATIENTS: Infants less than 1 year old with Risk Adjustment for Congenital Heart Surgery category 4, 5, 6, or d-transposition of great arteries (Risk Adjustment for Congenital Heart Surgery 3) consecutively treated during 2010 through 2013. INTERVENTION: A quality improvement process implemented in 2011 to decrease routine laboratory testing after surgery. MEASUREMENTS AND MAIN RESULTS: Fifty-two infants preintervention and 214 postintervention had similar age, weight, proportion of cyanotic lesions, and surgical complexity. Infants with single versus biventricular physiology were compared separately. The number of laboratory tests per patient adjusted for cardiac ICU length of stay (laboratory tests/patient/day) was significantly lower in postintervention populations for single and biventricular groups (9 vs 15 and 10 vs 15, respectively; p < 0.001). The proportion of single ventricle patients transfused post- and preintervention was not statistically different (72% vs 90%; p = 0.130). Transfusion in the biventricular groups was the same over time (65% vs 65%). Time to first transfusion was significantly longer in the postintervention single ventricle group (4 vs 1 d; p < 0.001), and was not statistically different in the biventricular patients (4 vs 7 d; p = 0.058). The median hematocrit level at first transfusion was significantly lower (37% vs 40%; p = 0.004) postintervention in the cyanotic population, but did not differ in the biventricular group (31% vs 31%; p = 0.840). CONCLUSION: In infants after heart surgery, blood testing targeted to individual needs significantly decreased the number of blood tests, but did not significantly decrease postoperative blood transfusion. PMID- 27662565 TI - Short-Term Health-Related Quality of Life of Critically Ill Children Following Daily Sedation Interruption. AB - OBJECTIVE: Our earlier pediatric daily sedation interruption trial showed that daily sedation interruption in addition to protocolized sedation in critically ill children does not reduce duration of mechanical ventilation, length of stay, or amounts of sedative drugs administered when compared with protocolized sedation only, but undersedation was more frequent in the daily sedation interruption + protocolized sedation group. We now report the preplanned analysis comparing short-term health-related quality of life and posttraumatic stress symptoms between the two groups. DESIGN: Preplanned prospective part of a randomized controlled trial. SETTING: Two tertiary medical-surgical PICUs in the Netherlands. PATIENTS: Critically ill children requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight weeks after a child's discharge from the PICU, health-related quality of life was assessed with the validated Child Health Questionnaire and, only for children above 4 years old, posttraumatic stress was assessed with the Dutch Children's Responses to Trauma Inventory. Additionally, health-related quality of life of all study patients was compared with Dutch normative data. Of the 113 patients from two participating centers in the original study, 96 patients were eligible for follow-up and 64 patients were included (response rate, 67%). No difference was found with respect to health-related quality of life between the two study groups. None of the eight children more than 4 years old showed posttraumatic stress symptoms. CONCLUSIONS: Daily sedation interruption in addition to protocolized sedation for critically ill children did not seem to have an effect on short-term health-related quality of life. Also in view of the earlier found absence of effect on clinical outcome, we cannot recommend the use of daily sedation interruption + protocolized sedation. PMID- 27662566 TI - Prediction of Catheter-Associated Thrombosis in Critically Ill Children. AB - OBJECTIVE: We determined whether in critically ill children with an untunneled central venous catheter, the risk of catheter-associated deep venous thrombosis can be predicted within 24 hours after insertion of the catheter. DESIGN: Secondary analysis of two multicenter prospective cohort studies. SETTING: PICUs in Northeastern United States. PATIENTS: A total of 175 children admitted to the PICU within 24 hours after insertion of an untunneled central venous catheter who did not receive anticoagulation were included. Of these, 53 (30.3%) developed catheter-associated thrombosis detected with active surveillance with ultrasonography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used logistic regression (models 1 and 2) and recursive partitioning (models 3 and 4) methods to develop risk prediction models with predictors present at any time while catheterized (models 1 and 3), or within 24 hours after insertion of the catheter (models 2 and 4). Age, recent surgery, catheter in the subclavian vein, and blood product transfusion were included in models 1 and 2. Areas under the receiver operating characteristic curves were similar for these models (model 1: 0.80 vs model 2: 0.80; p = 0.44). Except for recent surgery, predictors in model 1 were identified as partitioning variables for model 3. In addition to the predictors in model 2, severity of illness was used in partitioning for model 4. The area under the curve of model 3 appeared smaller than that of model 4 (0.75 vs 0.80; p = 0.08). Groups of children at low, intermediate, and high risks of catheter-associated thrombosis were identified using model 4. CONCLUSIONS: Critically ill children at high risk of catheter-associated thrombosis can be identified within 24 hours after insertion of an untunneled central venous catheter. PMID- 27662567 TI - Antithrombin Concentrate Use in Pediatric Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study. AB - OBJECTIVE: To describe antithrombin concentrate use and to compare thrombotic and hemorrhagic outcomes throughout the hospital stay in pediatric subjects who received extracorporeal membrane oxygenation in a Pediatric Health Information System-participating children's hospital. DESIGN: Retrospective, multi-center, cohort study. SETTING: Forty-three free-standing children's hospitals participating in Pediatric Health Information System. SUBJECTS: Children older than or equal to 18 years of age who underwent extracorporeal membrane oxygenation between 2003 and 2012. INTERVENTIONS: Subjects were classified as receiving antithrombin if they received at least one dose of antithrombin while on extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: International Classification of Diseases, Ninth Revision, Clinical Modification codes codes were used to identify hemorrhagic and thrombotic complications during their hospitalization. Pediatric Health Information System data were analyzed to determine hospital-length of stay and in-hospital mortality. A total of 1,931 of 8,601 eligible subjects (21.5%) received at least one dose of antithrombin during their extracorporeal membrane oxygenation course. Antithrombin use during extracorporeal membrane oxygenation increased from 2.4% to 51.9% (p < 0.001) over the 10-year study period. Subjects who received antithrombin while on extracorporeal membrane oxygenation were younger (p = 0.02), had more chronic conditions (p < 0.001), and longer hospital stays (p < 0.001). On multivariate analysis, antithrombin use was associated with thrombotic events (odds ratio, 1.55; 95% CI, 1.36-1.77; p < 0.001), hemorrhagic events (odds ratio, 1.27; 95% CI, 1.14-1.42; p < 0.001), and longer hospital length of stays (slope coefficient, 1.05 d; 95% CI, 1.04-1.06; p < 0.001). No difference was observed in mortality (odds ratio, 0.99; 95% CI, 0.89-1.11; p = 0.90). CONCLUSIONS: In this multicenter retrospective cohort study, subjects who received antithrombin during extracorporeal membrane oxygenation had a higher number of thrombotic and hemorrhagic events throughout the hospitalization and longer length of stays without an associated difference in mortality. While limitations exist with this analysis and results should be interpreted with caution, the fact remains that over half of pediatric patients on extracorporeal membrane oxygenation are currently receiving antithrombin without clear benefit, with extra cost, and potential harms, there needs to be strong consideration for a clinical trial. PMID- 27662568 TI - Evolution by flight and fight: diverse mechanisms of adaptation by actively motile microbes. AB - Evolutionary adaptation can be achieved by mechanisms accessible to all organisms, including faster growth and interference competition, but self generated motility offers additional possibilities. We tested whether 55 populations of the bacterium Myxococcus xanthus that underwent selection for increased fitness at the leading edge of swarming colonies adapted by swarming faster toward unused resources or by other means. Populations adapted greatly but diversified markedly in both swarming phenotypes and apparent mechanisms of adaptation. Intriguingly, although many adapted populations swarm intrinsically faster than their ancestors, numerous others do not. Some populations evolved interference competition toward their ancestors, whereas others gained the ability to facultatively increase swarming rate specifically upon direct interaction with ancestral competitors. Our results both highlight the diverse range of mechanisms by which actively motile organisms can adapt evolutionarily and help to explain the high levels of swarming-phenotype diversity found in local soil populations of M. xanthus. PMID- 27662569 TI - Systemic vasculitis and the eye. AB - PURPOSE OF REVIEW: The primary systemic vasculitides represent a spectrum of rare but life-threatening conditions that may also affect the eye in various forms. This article reviews recently published data on ocular manifestations of systemic vasculitis. RECENT FINDINGS: Early diagnosis and timely treatment has led to better visual outcomes in giant cell arteritis (GCA). Gene expression from orbital tissues could distinguish granulomatosis with polyangiitis (GPA) from sarcoidosis and Graves disease, but not from idiopathic orbital inflammation. Rituximab was an effective therapeutic option in ocular GPA. An ocular attack severity scoring system, flare levels, fluorescein angiography and optical coherence tomography parameters have been suggested as predictors of visual prognosis in Behcet disease. Efficacy of tumor necrosis factor-alpha inhibitors, interferon alpha and anti-interleukin-1 agents was shown in noncontrolled studies of ocular Behcet disease. SUMMARY: Widely used fast-track pathway care as well as ocular imaging to detect subclinical involvement may enable earlier diagnosis of GCA and prevention of permanent visual loss. Orbital inflammation may not remain idiopathic with advances in gene expression profiling of orbital tissues. With an increased availability and the use of biologic agents, visual prognosis will improve in patients with severe ocular complications of systemic vasculitides. PMID- 27662570 TI - Infections and vasculitis. AB - PURPOSE OF REVIEW: To review recent evidence for infection rates in patients with systemic vasculitides, the role of specific infectious agents in the pathogenesis of vasculitis and recent breakthroughs in the treatment of virus-associated vasculitides. RECENT FINDINGS: In well designed recent studies, infections were found to be common during the first 6-12 months in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) and giant cell arteritis (GCA) and to contribute significantly to increased mortality during this period. New therapeutic schemes with lower cyclophosphamide doses and shorter corticosteroid courses were associated with decreased infectious rates in elderly patients with AAV whereas a prednisone dose greater than 10 mg/day at the end of the first year were associated with increased infectious-related mortality in patients with GCA. Recently, a potential role for varicella zoster virus in GCA pathogenesis has been proposed but more data are needed in order to establish a causal relationship. Finally, preliminary data show excellent short-term efficacy and safety of the new, interferon-free, oral antiviral agents in the treatment of hepatitis C virus-associated cryoglobulinemic vasculitis. SUMMARY: Infections continue to be one of the main causes of mortality in patients with systemic vasculitides, emphasizing the need for safer immunosuppressive therapies and appropriate prophylaxis. PMID- 27662571 TI - Daily affect dynamics predict early response in CBT: Feasibility and predictive validity of EMA for outpatient psychotherapy. AB - BACKGROUND: Previous studies have shown that individual differences in affect dynamics during depressed patients' everyday lives allow the prediction of treatment outcome and of symptom reoccurrence in remitted patients. In this study, we analyze whether understanding patients' affective states and their fluctuation patterns helps predict early treatment response (until session 5). METHODS: Ecological Momentary Assessment (EMA) strategies allow in-depth analyses of real-time affective states and of their dynamics. Repeated assessments were made four times a day during a two-week period to capture real-life affective states (positive affect, PA and negative affect, NA) and dynamics (fluctuations in NA and PA) before the start of outpatient treatment of 39 patients. Due to the nested structure of the data, hierarchical linear models were conducted. RESULTS: PA/NA ratios, as well as fluctuations in NA predicted early treatment response, even when adjusting for initial impairment. In contrast, mean levels of NA or PA, as well as fluctuations in PA did not predict treatment response. LIMITATIONS: The time between the EMA assessment and treatment onset varied between patients. However, this variation was not associated with early change. CONCLUSIONS: The results suggest that pre-treatment affect dynamics could provide valuable information for predicting treatment response independent of initial impairment levels. Better predictions of early treatment response help to improve treatment choices early in the treatment progress. PMID- 27662572 TI - Trait-related alterations of N-acetylaspartate in euthymic bipolar patients: A longitudinal proton magnetic resonance spectroscopy study. AB - BACKGROUND: Neurochemical changes are responsible for bipolar disorder (BD) pathophysiology. Despite current progress in BD research, mood- and trait-related alterations in BD continue to elicit further investigation. METHODS: In this study, we report a longitudinal proton magnetic resonance spectroscopy study evaluating dorsomedial prefrontal cortex (DMPFC) metabolites N-acetylaspartate (NAA), creatine plus phosphocreatine (total creatine [tCr]), phosphorylcholine plus glycerophosphocholine, myo-inositol, and glutamate plus glutamine levels of manic and euthymic adult BD type I patients (n=48) treated with standard antimanic medicines, compared to matching healthy controls (n=44). RESULTS: DMPFC NAA values and NAA/tCr ratio were significantly lower in euthymic BD patients when compared with healthy controls with similar levels of other metabolites in all groups, indicating a trait-related NAA abnormality in euthymic BD patients. LIMITATIONS: of our study include a relatively low (1.5T) magnetic resonance field strength and variable drugs administered to achieve euthymia despite the best efforts to standardize the open fashion treatment. CONCLUSIONS: Our study contributes to the integrating models of trait-related metabolite alterations observed in euthymia since NAA is considered as a marker of neuronal viability and mitochondrial energy metabolism. In light of supporting and conflicting results reported previously, future studies with longitudinal designs and larger patient groups are warranted to better define both state- and trait-related cerebral metabolic alterations associated with BD pathophysiology. PMID- 27662573 TI - A Broad Set of Chromatin Factors Influences Splicing. AB - Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and how direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset of chromatin proteins, including histones and remodeling complexes like SWI/SNF. Yet, an unbiased RNAi screen revealed that the outcome of splicing is influenced by a much larger variety of chromatin factors not all associating with the spliceosome. The availability of this broad range of chromatin factors impacting splicing further unveiled their very context specific effect, resulting in either inclusion or skipping, depending on the exon under scrutiny. Finally, a direct assessment of the impact of chromatin on splicing using an in vitro co transcriptional splicing assay with pre-mRNAs transcribed from a nucleosomal template, demonstrated that chromatin impacts nascent pre-mRNP in their competence for splicing. Altogether, our data show that numerous chromatin factors associated or not with the spliceosome can affect the outcome of splicing, possibly as a function of the local chromatin environment that by default interferes with the efficiency of splicing. PMID- 27662574 TI - Positive Selection Drives Rapid Evolution of the meq Oncogene of Marek's Disease Virus. AB - Marek's disease (MD), caused by Marek's disease virus (MDV), a poultry-borne alphaherpesvirus, is a devastating disease of poultry causing an estimated annual loss of one billion dollars to poultry producers, worldwide. Despite decades of control through vaccination, MDV field strains continue to emerge having increased virulence. The evolutionary mechanism driving the emergence of this continuum of strains to increased MDV virulence, however, remains largely enigmatic. Increase in MDV virulence has been associated with specific amino acid changes within the C-terminus domain of Mareks's EcoRI-Q (meq)-encoded oncoprotein. In this study, we sought to determine whether the meq gene has evolved adaptively and whether past vaccination efforts have had any significant effect on the reduction or increase of MDV diversity over time. Our analysis suggests that meq is estimated to be evolving at a much faster rate than most dsDNA viruses, and is comparable with the evolutionary rate of RNA viruses. Interestingly, most of the polymorphisms in meq gene appear to have evolved under positive selection and the time of divergence at the meq locus coincides with the period during which the poultry industry had undergone transitions in management practices including the introduction and widespread use of live attenuated vaccines. Our study has revealed that the decades-long use of vaccines did not reduce MDV diversity, but rather had a stimulating effect on the emergence of field strains with increased genetic diversity until the early 2000s. During the years 2004-2005, there was an abrupt decline in the genetic diversity of field isolates followed by a recovery from this bottleneck in the year 2010. Collectively, these data suggest that vaccination seems to not have had any effect on MDV eradication, but rather had a stimulating effect on MDV emergence through adaptation. PMID- 27662576 TI - Radiation Dose Comparison Between 70 kVp and 100 kVp With Spectral Beam Shaping for Non-Contrast-Enhanced Pediatric Chest Computed Tomography: A Prospective Randomized Controlled Study. AB - OBJECTIVE: The aim of this prospective randomized controlled study was to compare 2 techniques for radiation dose reduction in non-contrast-enhanced pediatric chest computed tomography (CT): low peak kilovoltage imaging at 70 kVp and spectral beam shaping at 100 kVp using a dedicated tin filter (100-kVp Sn). MATERIALS AND METHODS: All chest CT examinations were performed on a third generation dual-source CT system (SOMATOM Force; Siemens Healthineers, Germany). Fifty children (mean age, 6.8 +/- 5.1 years) were examined using the 100-kVp Sn protocol, whereas 25 children received the 70-kVp protocol (mean age, 5.7 +/- 5.2 years; 2:1 randomization scheme). Radiation metrics and organ doses were compared between acquisition techniques using commercially available radiation dose analysis software (Radimetrics Inc, Bayer AG, Toronto, Ontario, Canada). Objective image quality, expressed by signal-to-noise ratio and subjective image quality based on a 4-point scale (1, best; 4, worst image quality), were compared. RESULTS: Volume CT dose index and size-specific dose estimate were significantly lower in the 100-kVp Sn group compared with the 70-kVp group (0.19 +/- 0.12 mGy vs 0.81 +/- 0.70 mGy and 0.34 +/- 0.13 mGy vs 1.48 +/- 1.11 mGy; P < 0.0001 for both). Accordingly, mean effective dose was significantly lower for the 100-kVp Sn examinations (0.21 +/- 0.10 mSv) compared with the 70-kVp examinations (0.83 +/- 0.49 mSv; P < 0.0001). Calculated organ doses were also significantly lower using the 100-kVp Sn protocol when compared with the 70-kVp protocol; for example, breast dose was reduced by a factor of 4.3. Signal-to noise ratio was slightly superior for 70-kVp images while lung image quality of the 100-kVp Sn protocol was preferred in subjective analysis (P = 0.0004). CONCLUSIONS: Pediatric chest CT performed at 100 kVp with an additional tin filter for spectral shaping significantly reduces radiation dose when compared with low peak kilovoltage imaging at 70 kVp and therefore should be preferred in non-contrast-enhanced pediatric chest CT examinations, particularly (given the improved subjective image quality) when the main focus is evaluation of the lung parenchyma. PMID- 27662577 TI - Simultaneous Multislice Diffusion-Weighted Imaging of the Kidney: A Systematic Analysis of Image Quality. AB - OBJECTIVES: The aims of this study were to implement a protocol for simultaneous multislice (SMS) accelerated diffusion-weighted imaging (DWI) of the kidneys and to perform a systematic analysis of image quality of the data sets. MATERIALS AND METHODS: Ten healthy subjects and 5 patients with renal masses underwent DWI of the kidney in this prospective institutional review board-approved study on a 3 T magnetic resonance scanner. Simultaneous multislice DWI echo-planar sequences (acceleration factors [AFs] 2 and 3) were compared with conventional echo-planar DWI as reference standard for each acquisition scheme. The following 3 acquisition schemes were applied: comparison A, with increased number of acquisitions at constant scan time; comparison B, with reduction of acquisition time; and comparison C, with increased slice resolution (constant acquisition time, increasing number of slices). Interreader reliability was analyzed by calculating the intraclass correlation coefficient (ICC). Qualitative image quality features were evaluated by 2 independent radiologists on a 5-point Likert scale. Quantification accuracy of the apparent diffusion coefficients (ADCs) and signal-to-noise ratios (SNRs) were assessed by region of interest analysis. Furthermore, lesion conspicuity in the 5 patients was assessed using a 5-point Likert scale by 2 independent radiologists. RESULTS: Interreader agreement was substantial with an ICC of 0.68 for the overall image quality and an ICC of 0.73 for the analysis of artifacts. In comparison A, AF2 resulted in increased SNR (P < 0.05) by 21% at stable image quality scores (image quality: P = 0.76, artifacts: P = 0.21). In comparison B, applying AF2, the scan time could be reduced by 46% without significant reduction in qualitative image quality scores (P = 0.059) or SNR (P = 0.126). In comparison C, slice resolution could be improved by 28% using AF2 with stable image quality scores and SNR. In general, AF3 resulted in reduced image quality and SNR. Significantly reduced ADC values were observed for AF3 in comparison C (cortex: P = 0.003; medulla: P = 0.001) compared with the standard echo-planar imaging sequence. The conventional DWI and the SMS DWI with AF2 showed stable lesion conspicuity ([AF1/AF2]: reader 1 [1.8/1.4] and reader 2 [1.8/1.4]). The lesion conspicuity was lower using AF3 (reader 1: 2.2 and reader 2: 1.8). CONCLUSIONS: In conclusion, SMS DWI of the kidney is a potential tool to substantially reduce scan time without negative effects on SNR, ADC quantification accuracy, and image quality if an AF2 is used. Although AF3 results in even higher scan time reduction, a negative impact on image quality, SNR, ADC quantification accuracy, and lesion conspicuity must be considered. PMID- 27662575 TI - Hyperpolarized 129Xenon Magnetic Resonance Imaging to Quantify Regional Ventilation Differences in Mild to Moderate Asthma: A Prospective Comparison Between Semiautomated Ventilation Defect Percentage Calculation and Pulmonary Function Tests. AB - OBJECTIVES: The aim of this study was to investigate ventilation in mild to moderate asthmatic patients and age-matched controls using hyperpolarized (HP) Xenon magnetic resonance imaging (MRI) and correlate findings with pulmonary function tests (PFTs). MATERIALS AND METHODS: This single-center, Health Insurance Portability and Accountability Act-compliant prospective study was approved by our institutional review board. Thirty subjects (10 young asthmatic patients, 26 +/- 6 years; 3 males, 7 females; 10 older asthmatic patients, 64 +/- 6 years; 3 males, 7 females; 10 healthy controls) were enrolled. After repeated PFTs 1 week apart, the subjects underwent 2 MRI scans within 10 minutes, inhaling 1-L volumes containing 0.5 to 1 L of Xe. Xe ventilation signal was quantified by linear binning, from which the ventilation defect percentage (VDP) was derived. Differences in VDP among subgroups and variability with age were evaluated using 1-tailed t tests. Correlation of VDP with PFTs was tested using Pearson correlation coefficient. Reproducibility of VDP was assessed using Bland-Altman plots, linear regression (R), intraclass correlation coefficient, and concordance correlation coefficient. RESULTS: Ventilation defect percentage was significantly higher in young asthmatic patients versus young healthy subjects (8.4% +/- 3.2% vs 5.6% +/- 1.7%, P = 0.031), but not in older asthmatic patients versus age matched controls (16.8% +/- 10.3% vs 11.6% +/- 6.6%, P = 0.13). Ventilation defect percentage was found to increase significantly with age (healthy, P = 0.05; asthmatic patients, P = 0.033). Ventilation defect percentage was highly reproducible (R = 0.976; intraclass correlation coefficient, 0.977; concordance correlation coefficient, 0.976) and significantly correlated with FEV1% (r = 0.42, P = 0.025), FEF25%-75% (r = -0.45, P = 0.019), FEV1/FVC (r = -0.71, P < 0.0001), FeNO (r = 0.69, P < 0.0001), and RV/TLC (r = 0.51, P = 0.0067). Bland Altman analysis showed a bias for VDP of -0.88 +/- 1.52 (FEV1%, -0.33 +/- 7.18). CONCLUSIONS: Xenon MRI is able to depict airway obstructions in mild to moderate asthma and significantly correlates with PFTs. PMID- 27662578 TI - Per2-Mediated Vascular Dysfunction Is Caused by the Upregulation of the Connective Tissue Growth Factor (CTGF). AB - Period 2-mutant mice (Per2m/m), which possess a circadian dysfunction, recapitulate the retinal vascular phenotype similar to diabetic retinopathy (DR). The vascular dysfunction in Per2m/m is associated with an increase in connective tissue growth factor (CTGF/CCN2). At the molecular level, CTGF gene expression is dependent on the canonical Wnt/beta-catenin pathway. The nuclear binding of beta catenin to a transcription factor, lymphoid enhancer binding protein (Lef)/ T cell factor (TCF/LEF), leads to downstream activation of CTGF. For this study, we hypothesized that the silencing of Per2 results in nuclear translocation and subsequent transactivation of the CTGF gene. To test this hypothesis, we performed immunofluorescence labeling for CTGF in retinal sections from wild-type (WT) and Per2m/m mice. Human retinal endothelial cells (HRECs) were transfected with siRNA for Per2, and the protein expression of CTGF and beta-catenin was evaluated. The TCF/LEF luciferase reporter (TOPflash) assay was performed to validate the involvement of beta-catenin in the activation of CTGF. Per2m/m retinas exhibited an increased CTGF immunostaining in ganglion cell layer and retinal endothelium. Silencing of Per2 using siRNA resulted in an upregulation of CTGF and beta-catenin. The TOPflash assay revealed an increase in luminescence for HRECs transfected with Per2 siRNA. Our studies show that loss of Per2 results in an activation of CTGF via nuclear entry of beta-catenin. Our study provides novel insight into the understanding of microvascular dysfunction in Per2m/m mice. PMID- 27662579 TI - Monocyte subsets in blood correlate with obesity related response of macrophages to biomaterials in vitro. AB - Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects the acute response of macrophages to biomaterials in vitro and whether this response is associated with biomarkers in blood. CD14 + monocytes were isolated from blood from obese and age and gender matched lean persons. Monocyte subsets were determined based on CD14 and CD16 on their surface. C-reactive protein (CRP) was measured in peripheral blood. The response of monocyte-derived macrophages to polypropylene (PP), polylactic acid (PLA), polyethylene terephthalate (PET) monofilament, and PET-multifilament (mPET) in culture was based on cytokine production. More IL-6 (for PET), less CCL18 (all materials) and IL-1ra (for PLA) was produced by macrophages from obese patients than lean subjects. Body mass index, serum CRP and to a lesser extend percentages of monocyte subtypes correlated with IL-6, TNFalpha, CCL18, and IL 1ra production. Taken together, monocyte-derived macrophages of obese patients respond more pro-inflammatory and less anti-inflammatory to biomaterials than macrophages from lean subjects, depending on the material. These results are a step towards personalized medicine for the development of a model or even a blood test to decide which biomaterial might be suitable for each patient. PMID- 27662582 TI - Metal-enhanced fluorescent dye-doped silica nanoparticles and magnetic separation: A sensitive platform for one-step fluorescence detection of prostate specific antigen. AB - The world health organization figures show prostate cancer in developed countries has been the second primary cause of cancer mortality following lung cancer for the men. So, early and sensitive diagnosis of cancer is very important before it spreads out to the other organs of the body. It is well-known that prostate specific antigen (PSA) is the most specific and efficient tumor marker for the diagnosis of prostate cancer. Herein, we successfully fabricated core-shell composite fluorescent nanoparticle Ag@SiO2@SiO2-RuBpy which provide a photoluminescence enhancement of up to ~3-fold when the separation distance between the surface of silver core and the center of the third RuBpy doped silica shell is about 10nm. These core-shell MEF-capable nanoparticles have obvious advantages. The interaction between the doped RuBpy molecules in the outer silica layer and the silver core, greatly improves the excitation efficiency and enhances the fluorescence intensity. Importantly, the presence of silica can reduce the self-quenching of RuBpy, which makes larger amounts of RuBpy incorporated into the silica shell. In addition, the shell protects the RuBpy against collisional quenching and irreversible photodegradation and provides abundant hydroxyl for easy conjugation. After that a highly sensitive, specific and reliable strategy based on metal-enhanced fluorescence and magnetic separation was applied for the detection of PSA in both buffer and serum. The process could be rapidly accomplished, in which the immunomagnetic nanospheres (IMNs) and immunofluorescent nanoparticles (IFNs) were used to capture and identify the target molecules simultaneously. A good linear relationship between the fluorescence intensity and the concentration of PSA (0.1-100ng/mL) with a detection limit 27pg/mL was obtained. PMID- 27662581 TI - Smartphone-based visualized microarray detection for multiplexed harmful substances in milk. AB - In this paper, we report a sensitive, simple and inexpensive analytical method for the immunoassay microarray based on a smartphone in which various harmful substances in milk could be assayed. Tetracyclines (TCs) and Quinolones (QNs) were selected as the model targets in this study. TCs and QNs antigens were immobilized in the microarray and then samples containing free of antibiotics and corresponding antibodies as well as AgNPs labeled secondary antibodies were added to the microarray. The signal of this competitive format was further amplified by silver enhancement technique based on the development reagents and achieved a visual dots in the array. The resulting microarray could be detected by the smartphone placed in the minicartridge. The limit of detection (LOD) of this novel detection platform was 1.51ngmL-1 (TCs) and 1.74ngmL-1 (QNs). To achieve one-well quantitative analysis, a series of gradient concentration mouse IgG was immobilized in the same well. As a result, an internal standard curve was plotted by the signal of different concentrations of mouse IgG. The results showed that a quantitative detection of TCs and QNs established were consistent with external standard curve. Compared to other methods, this method was superior in terms of detection limit, time saving, and one-well quantitative detected with smartphone which were simple sample-preparation. PMID- 27662583 TI - A surface enhanced Raman scattering quantitative analytical platform for detection of trace Cu coupled the catalytic reaction and gold nanoparticle aggregation with label-free Victoria blue B molecular probe. AB - With development of economy and society, there is an urgent need to develop convenient and sensitive methods for detection of Cu2+ pollution in water. In this article, a simple and sensitive SERS sensor was proposed to quantitative analysis of trace Cu2+ in water. The SERS sensor platform was prepared a common gold nanoparticle (AuNP)-SiO2 sol substrate platform by adsorbing HSA, coupling with the catalytic reaction of Cu2+-ascorbic acid (H2A)-dissolved oxygen, and using label-free Victoria blue B (VBB) as SERS molecular probes. The SERS sensor platform response to the AuNP aggregations by hydroxyl radicals (*OH) oxidizing from the Cu2+ catalytic reaction, which caused the SERS signal enhancement. Therefore, by monitoring the increase of SERS signal, Cu2+ in water can be determined accurately. The results show that the SERS sensor platforms owns a linear response with a range from 0.025 to 25MUmol/L Cu2+, and with a detection limit of 0.008MUmol/L. In addition, the SERS method demonstrated good specificity for Cu2+, which can determined accurately trace Cu2+ in water samples, and good recovery and accuracy are obtained for the water samples. With its high selectivity and good accuracy, the sensitive SERS quantitative analysis method is expected to be a promising candidate for determining copper ions in environmental monitoring and food safety. PMID- 27662584 TI - Generalization of skills between operant control and discrimination of EEG alpha. AB - While biofeedback is often said to increase self-control of physiological states by increasing awareness of their subjective correlates, relatively few studies have analyzed the relationship between control (standard biofeedback) and awareness (a discrimination paradigm). We hypothesized that the two skills would generalize and facilitate each other for 8-12Hz EEG amplitude (alpha). Participants were given 7 sessions of training to either control or discriminate Pz alpha followed by 3 sessions of the other paradigm. Another group was given 7 sessions with time divided equally between the two types of training. The control training first group showed significant generalization of skills to the discrimination task. However, the reverse was not true, and the combined task group did no better in either task than the other two groups. These results provide ambivalent support for the role of awareness in biofeedback, and suggest possible improvements in the discrimination paradigm. PMID- 27662580 TI - Impact of Chronic Stress Protocols in Learning and Memory in Rodents: Systematic Review and Meta-Analysis. AB - The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments. PMID- 27662585 TI - Biologically Informed Individual-Based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies. AB - Rift Valley fever (RVF) is a zoonotic disease endemic in sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is complex, involving humans, livestock, and multiple species of mosquitoes. The epidemiology of RVFV in endemic areas is strongly affected by climatic conditions and environmental variables. In this research, we adapt and use a network-based modeling framework to simulate the transmission of RVFV among hypothetical cattle operations in Kansas, US. Our model considers geo-located livestock populations at the individual level while incorporating the role of mosquito populations and the environment at a coarse resolution. Extensive simulations show the flexibility of our modeling framework when applied to specific scenarios to quantitatively evaluate the efficacy of mosquito control and livestock movement regulations in reducing the extent and intensity of RVF outbreaks in the United States. PMID- 27662588 TI - Correction: Measuring Faecal Epi-Androsterone as an Indicator of Gonadal Activity in Spotted Hyenas (Crocuta crocuta). AB - [This corrects the article DOI: 10.1371/journal.pone.0128706.]. PMID- 27662587 TI - Colonic biogeography in health and ulcerative colitis. AB - The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome. PMID- 27662586 TI - Limited prolonged effects of rifaximin treatment on irritable bowel syndrome related differences in the fecal microbiome and metabolome. AB - Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10-12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance ((1)H NMR) and gas chromatography-mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment. PMID- 27662590 TI - Knockdown of Serine-Arginine Protein Kinase 1 Inhibits the Growth and Migration in Renal Cell Carcinoma Cells. AB - The pre-mRNA splicing regulator serine-arginine protein kinase 1 (SRPK1), a member of the SR kinase family, plays an essential role in cancer development and various pathophysiological processes. However, its expression pattern and functions in renal cell carcinoma (RCC) remain unknown. Therefore, the aim of this study was to assess the role of SRPK1 in RCC. Our data showed that SRPK1 was significantly upregulated in human RCC tissues and cell lines. SRPK1 interference significantly inhibited the proliferation of RCC cells and inhibited tumor growth in vivo. In addition, SRPK1 interference also suppressed migration and invasion in RCC cells. A mechanistic study showed that SRPK1 interference inhibited the phosphorylation of PI3K and Akt in RCC cells. In conclusion, our findings suggest that SRPK1 interference inhibits the growth and invasion of RCC cells through suppressing the PI3K/Akt signaling pathway. Thus, SRPK1 might be a therapeutic target for the treatment of RCC. PMID- 27662591 TI - Mortality, Disenrollment, and Spending Persistence in Medicaid and CHIP. AB - BACKGROUND: Research on spending persistence has not focused on Medicaid and the Children's Health Insurance Program (Medicaid/CHIP), which includes a complex and growing population. OBJECTIVE OF THE STUDY: The objective of the study was to describe patterns of expenditure persistence, mortality, and disenrollment among nondually eligible Medicaid/CHIP enrollees and identify factors predicting these outcomes. RESEARCH DESIGN: The study is based on New Jersey Medicaid/CHIP claims data from 2011 to 2014. Descriptive and multinomial regression methods were used to characterize persistently extreme spenders, defined as those appearing in the top 1% of statewide spending every year, according to demographics, Medicaid/CHIP eligibility, nursing facility residence, patient risk scores, and clinical diagnostic categories measured in 2011. Similar analyses were done for persistently high spenders (ie, always in the top 10% but not always top 1%) as well as decedents, disenrollees, and moderate spenders (ie, at least 1 year outside of the top 10%). SUBJECTS: Nondually eligible NJ Medicaid/CHIP enrollees in 2011. RESULTS: One fourth of extreme spenders in 2011 remained in that category throughout 2011-2014. Almost all (89.3%) of the persistently extreme spenders were aged, blind, or disabled. Within the aged, blind, or disabled population, the strongest predictors of persistently extreme spending were diagnoses involving developmental disability, HIV/AIDS, central nervous system conditions, psychiatric disorders, type 1 diabetes, and renal conditions. Individuals in nursing facilities and those with very high risk scores were more likely to die or have persistently high spending than to have persistently extreme spending. CONCLUSIONS: The study highlights unique features of spending persistence within Medicaid/CHIP and provides methodological contributions to the broader persistence literature. PMID- 27662589 TI - An individual differences analysis of the neurocognitive architecture of the semantic system at rest. AB - Efficient semantic cognition depends on accessing and selecting conceptual knowledge relevant to the current task or context. This study explored the neurocognitive architecture that supports this function by examining how individual variation in functional brain organisation predicts comprehension and semantic generation. Participants underwent resting state functional magnetic resonance imaging (fMRI) and, on separate days, performed written synonym judgement, and letter and category fluency tasks. We found that better synonym judgement for high frequency items was linked to greater functional coupling between posterior fusiform and anterior superior temporal cortex (aSTG), which might index orthographic-to-semantic access. However, stronger coupling between aSTG and ventromedial prefrontal cortex was associated with poor performance on the same trials, potentially reflecting greater difficulty in focussing retrieval on relevant features for high frequency items that appear in a greater range of contexts. Fluency performance was instead linked to variations in the functional coupling of the inferior frontal gyrus (IFG); anterior IFG was more coupled to regions of primary visual cortex for individuals who were good at category fluency, while poor letter fluency was predicted by stronger coupling between posterior IFG and retrosplenial cortex. These results show that individual differences in functional connectivity at rest predict semantic performance and are consistent with a component process account of semantic cognition in which representational information is shaped by control processes to fit the current requirements, in both comprehension and fluency tasks. PMID- 27662592 TI - Maternally Derived Immunity Extends Swine Influenza A Virus Persistence within Farrow-to-Finish Pig Farms: Insights from a Stochastic Event-Driven Metapopulation Model. AB - Swine Influenza A Viruses (swIAVs) have been shown to persist in farrow-to-finish pig herds with repeated outbreaks in successive batches, increasing the risk for respiratory disorders in affected animals and being a threat for public health. Although the general routes of swIAV transmission (i.e. direct contact and exposure to aerosols) were clearly identified, the transmission process between batches is still not fully understood. Maternally derived antibodies (MDAs) were stressed as a possible factor favoring within-herd swIAV persistence. However, the relationship between MDAs and the global spread among the different subpopulations in the herds is still lacking. The aim of this study was therefore to understand the mechanisms induced by MDAs in relation with swIAV spread and persistence in farrow-to-finish pig herds. A metapopulation model has been developed representing the population dynamics considering two subpopulations breeding sows and growing pigs-managed according to batch-rearing system. This model was coupled with a swIAV-specific epidemiological model, accounting for partial passive immunity protection in neonatal piglets and an immunity boost in re-infected animals. Airborne transmission was included by a between-room transmission rate related to the current prevalence of shedding pigs. Maternally derived partial immunity in piglets was found to extend the duration of the epidemics within their batch, allowing for efficient between-batch transmission and resulting in longer swIAV persistence at the herd level. These results should be taken into account in the design of control programmes for the spread and persistence of swIAV in swine herds. PMID- 27662593 TI - The Wide Distribution and Change of Target Specificity of R2 Non-LTR Retrotransposons in Animals. AB - Transposons, or transposable elements, are the major components of genomes in most eukaryotes. Some groups of transposons have developed target specificity that limits the integration sites to a specific nonessential sequence or a genomic region to avoid gene disruption caused by insertion into an essential gene. R2 is one of the most intensively investigated groups of sequence-specific non-LTR retrotransposons and is inserted at a specific site inside of 28S ribosomal RNA (rRNA) genes. R2 is known to be distributed among at least six animal phyla even though its occurrence is reported to be patchy. Here, in order to obtain a more detailed picture of the distribution of R2, we surveyed R2 using both in silico screening and degenerate PCR, particularly focusing on actinopterygian fish. We found two families of the R2C lineage from vertebrates, although it has previously only been found in platyhelminthes. We also revealed the apparent movement of insertion sites of a lineage of actinopterygian R2, which was likely concurrent with the acquisition of a 28S rRNA-derived sequence in their 3' UTR. Outside of actinopterygian fish, we revealed the maintenance of a single R2 lineage in birds; the co-existence of four lineages of R2 in the leafcutter bee Megachile rotundata; the first examples of R2 in Ctenophora, Mollusca, and Hemichordata; and two families of R2 showing no target specificity. These findings indicate that R2 is relatively stable and universal, while differences in the distribution and maintenance of R2 lineages probably reflect characteristics of some combination of both R2 lineages and host organisms. PMID- 27662594 TI - Morphological Response of Eight Quercus Species to Simulated Wind Load. AB - Leaf shape, including leaf size, leaf dissection index (LDI), and venation distribution, strongly impacts leaf physiology and the forces of momentum exerted on leaves or the canopy under windy conditions. Yet, little has been known about how leaf shape affects the morphological response of trees to wind load. We studied eight Quercus species, with different leaf shapes, to determine the morphological response to simulated wind load. Quercus trees with long elliptical leaves, were significantly affected by wind load (P< 0.05), as indicted by smaller specific leaf area (SLA), stem base diameter and stem height under windy conditions when compared to the control. The Quercus trees with leaves characterized by lanceolate or sinuous edges, showed positive morphological responses to wind load, such as bigger leaf thickness, larger stem diameter, allocation to root biomass, and smaller stem height (P< 0.05). These morphological responses to wind can reduce drag and increase the mechanical strength of the tree. Leaf dissection index (LDI), an important index of leaf shape, was correlated with morphological response to wind load (P< 0.05), including differences in SLA, in stem base diameter and in allocation to root biomass. These results suggest that trees with higher LDI, such as those with more and/or deeper lobes, are better adapted to wind load. PMID- 27662595 TI - Commentary: Can We See the Forest for the IVs?: Mendelian Randomization Studies with Multiple Genetic Variants. PMID- 27662596 TI - Immunosuppressive effect of ASP2408, a novel CD86-selective variant of CTLA4-Ig, in rats and cynomolgus monkeys. AB - The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods. Here we evaluated the effect of ASP2408 in vitro using cynomolgus monkey and rat T cell proliferation assays and in vivo using cynomolgus monkey tetanus toxoid (TTx) immunization and a rat rheumatoid arthritis model. ASP2408 was 290-fold and 21-fold more potent in suppressing in vitro monkey T cell proliferation than abatacept and belatacept, respectively. ASP2408 inhibited anti-TTx immunological reactions in cynomolgus monkey at a 10 fold lower dose level than belatacept, through complete CD86 and partial CD80 receptor occupancies, and also suppressed inflammation in the rat collagen induced arthritis model. Overall, improved immunosuppressive potency of ASP2408 relative to abatacept and belatacept correlated well with improved CD86 binding affinity. These results may support the advantage of preferential enhancement of CD86 binding affinity to inhibit T cell-mediated immune response and improved dosing convenience in humans relative to abatacept or belatacept. PMID- 27662598 TI - Epidemiology of eating disorders in Europe: prevalence, incidence, comorbidity, course, consequences, and risk factors. AB - PURPOSE OF REVIEW: Eating disorders - anorexia nervosa, bulimia nervosa, and binge eating disorder - affect numerous Europeans. This narrative review summarizes European studies on their prevalence, incidence, comorbidity, course, consequences, and risk factors published in 2015 and the first half of 2016. RECENT FINDINGS: Anorexia nervosa is reported by <1-4%, bulimia nervosa <1-2%, binge eating disorder <1-4%, and subthreshold eating disorders by 2-3% of women in Europe. Of men, 0.3-0.7% report eating disorders. Incidences of anorexia appear stable, whereas bulimia may be declining. Although the numbers of individuals receiving treatment have increased, only about one-third is detected by healthcare. Over 70% of individuals with eating disorders report comorbid disorders: anxiety disorders (>50%), mood disorders (>40%), self-harm (>20%), and substance use (>10%) are common. The long-term course of anorexia nervosa is favorable for most, but a substantial minority of eating disorder patients experience longstanding symptoms and somatic problems. The risk of suicide is elevated. Parental psychiatric disorders, prenatal maternal stress, various family factors, childhood overweight, and body dissatisfaction in adolescence increase the risk of eating disorders. SUMMARY: Eating disorders are relatively common disorders that are often overlooked, although they are associated with high comorbidity and serious health consequences. PMID- 27662597 TI - Probabilistic tractography using Lasso bootstrap. AB - Diffusion magnetic resonance imaging (dMRI) can be used for noninvasive imaging of white matter tracts. Using fiber tracking, which propagates fiber streamlines according to fiber orientations (FOs) computed from dMRI, white matter tracts can be reconstructed for investigation of brain diseases and the brain connectome. Because of image noise, probabilistic tractography has been proposed to characterize uncertainties in FO estimation. Bootstrap provides a nonparametric approach to the estimation of FO uncertainties and residual bootstrap has been used for developing probabilistic tractography. However, recently developed models have incorporated sparsity regularization to reduce the required number of gradient directions to resolve crossing FOs, and the residual bootstrap used in previous methods is not applicable to these models. In this work, we propose a probabilistic tractography algorithm named Lasso bootstrap tractography (LBT) for the models that incorporate sparsity. Using a fixed tensor basis and a sparsity assumption, diffusion signals are modeled using a Lasso formulation. With the residuals from the Lasso model, a distribution of diffusion signals is obtained according to a modified Lasso bootstrap strategy. FOs are then estimated from the synthesized diffusion signals by an algorithm that improves FO estimation by enforcing spatial consistency of FOs. Finally, streamlining fiber tracking is performed with the computed FOs. The LBT algorithm was evaluated on simulated and real dMRI data both qualitatively and quantitatively. Results demonstrate that LBT outperforms state-of-the-art algorithms. PMID- 27662599 TI - Density Functional Theory Analysis of Anthraquinone Derivative Hydrogenation over Palladium Catalyst. AB - A density functional theory (DFT) analysis was conducted on the hydrogenation of 2-alkyl-anthraquinone (AQ), including 2-ethyl-9,10-anthraquinone (eAQ) and 2 ethyl-5,6,7,8-tetrahydro-9,10-anthraquinone (H4 eAQ), to the corresponding anthrahydroquinone (AQH2 ) over a Pd6 H2 cluster. Hydrogenation of H4 eAQ is suggested to be more favorable than that of eAQ owing to a higher adsorption energy of the reactant (H4 eAQ), lower barrier of activation energy, and smaller desorption energy of the target product (2-ethyl-5,6,7,8-tetrahydro-9,10 anthrahydroquinone, H4 eAQH2 ). For the most probable reaction routes, the energy barrier of the second hydrogenation step of AQ is circa 8 kcal mol-1 higher than that of the first step. Electron transfer of these processes were systematically investigated. Facile electron transfer from Pd6 H2 cluster to AQ/AQH intermediate favors the hydrogenation of C=O. The electron delocalization over the boundary aromatic ring of AQ/AQH intermediate and the electron-withdrawing effect of C=O are responsible for the electron transfer. In addition, a pathway of the electron transfer is proposed for the adsorption and subsequent hydrogenation of AQ on the surface of Pd6 H2 cluster. The electron transfers from the abstracted H atom (reactive H) to a neighbor Pd atom (PdH ), and finally goes to the carbonyl group through the C4 atom of AQ aromatic ring (C4 ). PMID- 27662600 TI - Ambulant management of acute tonsillitis in adult patients, a study on 330 patients. PMID- 27662601 TI - Unexpected Neuroprotective Effects of Loganin on 1-Methyl-4-Phenyl-1,2,3,6 Tetrahydropyridine-Induced Neurotoxicity and Cell Death in Zebrafish. AB - 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development. Loganin could block MPTP-induced defects, with little toxicity to the eggs. Results of whole mount in situ hybridization showed loganin prevented the loss of both dopaminergic neurons and locomotor activity, exhibited by larvae treated with MPTP. In addition, loganin significantly rescued MPTP induced neurotoxicity on PC12 cells, possibly through the suppression of PI3K/Akt/mTOR axis and JNK signaling pathways. In conclusion, loganin blocks MPTP induced neurotoxicity and abnormal development in zebrafish. J. Cell. Biochem. 118: 615-628, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662602 TI - Role of Protein Kinase G and Reactive Oxygen Species in the Regulation of Podocyte Function in Health and Disease. AB - Podocytes and their foot processes form an important cellular layer of the glomerular barrier involved in the regulation of glomerular permeability. Disturbing the function of podocytes plays a central role in the development of proteinuria in diabetic nephropathy. Retraction of the podocyte foot processes that form slit diaphragms is a common feature of proteinuria; although, the correlation between these events in not well understood. Notably, it is unclear whether podocyte foot processes are able to regulate slit diaphragm permeability and glomerular ultrafiltration. The occurrence of reactive oxygen species generation, insulin resistance, and hyperglycemia characterizes early stages of type 2 diabetes. Protein kinase G type I alpha (PKGIalpha) is an intracellular target for vasorelaxant factors. It is activated in both cGMP-dependent and cGMP independent manners. Recently, we demonstrated a relationship between oxidative stress, PKGIalpha activation, actin reorganization, and changes in the permeability of the filtration barrier. This review discusses how redox imbalance affects both the activity of PKGIalpha and PKGI-dependent signaling pathways in podocytes. J. Cell. Physiol. 232: 691-697, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662603 TI - Role of VR1 in the differentiation of bone marrow-derived mesenchymal stem cells into cardiomyocytes associated with Wnt/beta-catenin signaling. AB - AIM: Accumulating evidence showed that transient receptor potential channels play an important role in the regulation of cardiomyocyte differentiation. The vanilloid receptor 1 (VR1) is a member of the transient receptor channel super family and is expressed in cardiomyocytes. However, its function in cardiomyocytes remains unclear. METHODS: Herein, the aim of this study was to investigate the functional role of VR1 in the cardiomyocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and to elucidate the potential molecular mechanisms. RESULTS: Immunofluorescence assay showed that cardiomyocyte marker cardiac troponin T (cTnT) was found significantly elevated in differentiated BMSCs induced by 5-azacytidine compared with control. Similarly, VR1 expression was also found significantly increased in induced BMSCs differentiation. Additionally, we examined the role of VR1 in BMSC differentiation processes through VR1 siRNAs. We found that the expression of cardiomyocyte marker genes, such as alpha-myosin heavy chain (alpha-MHC), alpha cardiac actin, and Nkx2.5 (cardiac-specific transcription factor), was significantly decreased when VR1 was silenced. Furthermore, we found that inhibition of VR1 expression is associated with downregulation of Wnt/beta catenin signaling. CONCLUSIONS: To summarize, our data demonstrate important role of VR1 in BMSCs differentiation into cardiomyocytes in conjunction of Wnt/beta catenin signaling. PMID- 27662604 TI - Prognosis of Indirect Composite Resin Cuspal Coverage on Endodontically Treated Premolars and Molars: An In Vivo Prospective Study. AB - PURPOSE: This prospective clinical study evaluated the success rate of indirect composite resin cuspal coverage on endodontically treated molars and premolars and the survival rate of the restored teeth. MATERIALS AND METHODS: One hundred fifty endodontically treated teeth were restored with total resin cuspal coverage and randomly selected for the study. Patients were recalled after 2 to 5 years for clinical evaluation. Data were subjected to standard tests of statistical correlations using Spearman test. RESULTS: Out of the 150 teeth, 84 were molars and 66 were premolars. Of these teeth, 58.7% had mesio-occlusal-distal (MOD) cavities, 20.7% had mesio-occlusal (MO), and 20.7% had occlusal-distal (OD). A build-up procedure was performed in 51.3% of the teeth, and buccal veneer composite resins were placed at the margins of 96.7% of the teeth. Out of the 150 teeth, 30 (20%) presented margin discoloration, 3 teeth (2%) had restoration reparable fractures, 2 teeth (1.3%) had restoration irreparable fractures, and 1 tooth (0.7%) exhibited secondary recurrent caries. The opposing arch that occluded with the treated teeth presented 58% natural teeth (no restoration material), 26.7% ceramic crowns, and 15.3% implant-supported ceramic crowns. Statistically significant differences (p = 0.018) between irreparable restoration fractures and the type of support material present in the opposing arch were found. CONCLUSIONS: In a period of up to 5 years, the resin cuspal coverage of endodontic treated teeth had a success rate of 96%, while the tooth survival rate was 100%. The type of support material on the opposing arch may influence the longevity of the restoration of endodontically treated teeth. PMID- 27662605 TI - Post-instrumentation pain after the use of either Mtwo or the SAF system: a randomized controlled clinical trial. AB - AIM: This randomized controlled trial compared the incidence of post instrumentation pain associated with Mtwo rotary NiTi files and the self adjusting file system following canal shaping and cleaning. METHODOLOGY: Following sample size estimation, a total of 130 patients were randomized into two groups based on selection criteria [group Mtwo and group SAF (self-adjusting file)]. Root canal treatment was carried out in two appointments. The teeth were endodontically treated with the appropriate allotted systems following the similar clinical parameters. Patients were asked to rate the intensity of pre instrumentation and post-instrumentation pain (at 2, 4, 6, 8, 24, 48 h) using the VAS score. The Kruskal-Wallis test was carried out for the overall comparisons of the two systems. The Friedman test was used to compare between time-points with each system. Subgroup analyses for independent variables (gender, pulp status and diagnosis) used the Mann-Whitney test and Wilcoxon signed ranks test (P < 0.05). RESULTS: No significant difference was found between the two groups with respect to post-instrumentation pain. Teeth with pulpal necrosis had significant pain at 8 h compared with teeth with vital pulps (P = 0.04). Teeth with vital pulps in the SAF group had significantly less post-instrumentation pain compared with those in the Mtwo group at 6 h (P = 0.042). Patients who had teeth with nonvital pulps in the SAF group experienced more post-instrumentation pain at 8 h (P = 0.017) and 24 h (P = 0.005). CONCLUSION: The incidence of post-instrumentation pain at different time intervals in patients undergoing root canal treatment was similar for both the self-adjusting file and Mtwo file systems. PMID- 27662606 TI - Impact of Anatomy Boot Camp on Students in a Medical Gross Anatomy Course. AB - Lincoln Memorial University-DeBusk College of Osteopathic Medicine (LMU-DCOM) offers an optional three-week summer Anatomy Boot Camp course (ABC) to facilitate students' transition into medical school and promote retention of anatomy subject matter. The pre-matriculation program is a supplemental instruction course that utilizes a small group learning format. Boot camp instruction is led by teaching assistants and two anatomy professors. Enrollees gain early exposure to Medical Gross Anatomy (MGA) course subject matter, which is taught in the fall semester, and learn study skills necessary to excel in medical school. No grade is assigned for the course, therefore participants can study without the fear of potentially affecting grades. This study evaluates the effectiveness of the LMU-DCOM ABC course using data from four consecutive summers. Independent two-sample t-tests were used to compare ABC to non-ABC students for the following variables: incoming grade point average (GPA) and Medical College Admission Test(r) (MCAT(r)) scores, MGA written and laboratory practical examination grades, and final MGA course grade. Additionally, a 26-question survey was administered to 2012-2014 boot camp participants. There were no significant differences in incoming GPA and MCAT scores. However, boot campers scored significantly higher on the first two lecture and laboratory examinations (P < 0.05) for each year of the study. Thereafter scores varied less, suggesting a faster head start for boot camp participants. Mean MGA final grade was on average 3% higher for the boot camp cohort. The survey feedback supports that the ABC course assists with the academic and social transition into medical school. Anat Sci Educ 10: 215-223. (c) 2016 American Association of Anatomists. PMID- 27662607 TI - Is telomere length a molecular marker of past thermal stress in wild fish? AB - Telomeres protect eukaryotic chromosomes; variation in telomere length has been linked (primarily in homoeothermic animals) to variation in stress, cellular ageing and disease risk. Moreover, telomeres have been suggested to function as biomarker for quantifying past environmental stress, but studies in wild animals remain rare. Environmental stress, such as extreme environmental temperatures in poikilothermic animals, may result in oxidative stress that accelerates telomere attrition. However, growth, which may depend on temperature, can also contribute to telomere attrition. To test for associations between multitissue telomere length and past water temperature while accounting for the previous individual growth, we used quantitative PCR to analyse samples from 112 young-of-the-year brown trout from 10 natural rivers with average water temperature differences of up to 6 degrees C (and an absolute maximum of 23 degrees C). We found negative associations between relative telomere length (RTL) and both average river temperature and individual body size. We found no indication of RTL-temperature association differences among six tissues, but we did find indications for differences among the tissues for associations between RTL and body size; size trends, albeit nonsignificant in their differences, were strongest in muscle and weakest in fin. Although causal relationships among temperature, growth, oxidative stress, and cross-sectional telomere length remain largely unknown, our results indicate that telomere-length variation in a poikilothermic wild animal is associated with both past temperature and growth. PMID- 27662608 TI - High standards for high dimensional investigations. PMID- 27662609 TI - Cationic Platinum(II) sigma-SiH Complexes in Carbon Dioxide Hydrosilation. AB - The low-electron-count cationic platinum complex [Pt(ItBu')(ItBu)][BArF ], 1, interacts with primary and secondary silanes to form the corresponding sigma-SiH complexes. According to DFT calculations, the most stable coordination mode is the uncommon eta1 -SiH. The reaction of 1 with Et2 SiH2 leads to the X-ray structurally characterized 14-electron PtII species [Pt(SiEt2 H)(ItBu)2 ][BArF ], 2, which is stabilized by an agostic interaction. Complexes 1, 2, and the hydride [Pt(H)(ItBu)2 ][BArF ], 3, catalyze the hydrosilation of CO2 , leading to the exclusive formation of the corresponding silyl formates at room temperature. PMID- 27662610 TI - Convergence in organ size but not energy metabolism enzyme activities among wild Lake Whitefish (Coregonus clupeaformis) species pairs. AB - The repeated evolution of similar phenotypes by similar mechanisms can be indicative of local adaptation, constraints or biases in the evolutionary process. Little is known about the incidence of physiological convergence in natural populations, so here we test whether energy metabolism in 'dwarf' and 'normal' Lake Whitefish evolves by similar mechanisms. Prior genomic and transcriptomic studies have found that divergence in energy metabolism is key to local adaptation in whitefish species pairs, but that distinct genetic and transcriptomic changes often underlie phenotypic evolution among lakes. Here, we predicted that traits at higher levels of biological organization, including the activities of energy metabolism enzymes (the product of enzyme concentration and turnover rate) and the relative proportions of metabolically active tissues (heart, liver, skeletal muscle), would show greater convergence than genetic and transcriptomic variation. We compared four whitefish species pairs and found convergence in organ size whereby all dwarf whitefish populations have a higher proportion of red skeletal muscle, three have relatively larger livers and two have relatively larger ventricles than normal fish. On the other hand, hepatic and muscle enzyme activities showed little convergence and were largely dependent on lake of origin. Only the most genetically divergent species pair (Cliff Lake) displayed white muscle enzyme activities matching results from laboratory-reared normal and dwarf whitefish. Overall, these data show convergence in the evolution of organ size, but not in the activities of candidate enzymes of energy metabolism, which may have evolved mainly as a consequence of demographic or ecological differences among lakes. PMID- 27662611 TI - Feasibility of BAALC gene expression for detection of minimal residual disease and risk stratification in normal karyotype acute myeloid leukaemia. AB - High BAALC gene expression has been associated with poor prognosis in cytogenetically normal acute myeloid leukaemia (CN-AML) and has been suggested as a suitable marker for assessing minimal residual disease (MRD). The purpose of this study was to substantiate these findings by the analysis of a large data set of 632 diagnostic and follow-up samples in 142 intensively treated CN-AML patients. Paired diagnostic/relapse samples of 35 patients revealed stable high BAALC expression in 89%, irrespective of a high proportion of clonal evolution found in 49% of these cases. High BAALC expression, both directly after induction chemotherapy and within 3-6 months after induction chemotherapy, correlated significantly with shorter event-free survival and overall survival. Moreover, 8 of 10 patients displaying high BAALC expression levels after completion of induction therapy as well as 5 of 5 patients exhibiting high BAALC expression levels within 3-6 months after induction chemotherapy experienced relapse with a median of 197 and 101 days, respectively, from sampling to relapse. Thus, BAALC expression-based MRD detection during therapy may be considered a strategy to identify patients at high risk of relapse. PMID- 27662612 TI - Avian Influenza Virus H5 Strain with North American and Eurasian Lineage Genes in an Antarctic Penguin. PMID- 27662613 TI - Is smoking tobacco associated with psychotic experiences across racial categories in the United States? Findings from the Collaborative Psychiatric Epidemiological Surveys. AB - Smoking tobacco has been associated with psychosis, though research has yet to fully examine the extent to which this association reaches into the sub-threshold range of the psychosis continuum within the US, and whether this association persists after accounting for co-occurring disorders. We analyzed data from three large racially-diverse surveys of the US population and found that current smokers were more likely to report a lifetime psychotic experience when compared with never smokers after adjusting for socio-demographics. But after controlling for anxiety, mood, and substance use disorders, these effects only remained strong and statistically significant for Asian-Americans. PMID- 27662614 TI - Adverse childhood experiences and association with health, mental health, and risky behavior in the kingdom of Saudi Arabia. AB - BACKGROUND: The aim of this study is to determine if ACEs impact the health and risk behavior burden among Kingdom of Saudi Arabia (KSA) adults. METHODS: In 2013, a cross-sectional study was conducted across KSA to identify the retrospective prevalence of ACEs and their association with high risk behaviors and chronic diseases. Surveys from 10,156 adults in all 13 Saudi regions were obtained using an Arabic version of the WHO ACE-IQ (KSA ACE-IQ). RESULTS: Compared to respondents reporting no ACEs, even just one ACE contributed significantly to the odds of experiencing diabetes mellitus (OR=1.3), depression (OR=1.32), or anxiety (OR=1.79) outcomes. Two ACEs were necessary for statistically significant, higher odds to emerge for hypertension (OR=1.46), mental illness (OR=1.93), smoking (OR=1.17), alcohol use (OR=1.75), and drug use (OR=1.45). Respondents who reported four or more ACEs had greater odds of coronary heart disease (OR=1.94), and obesity (OR=2.25). Compared to those reporting no ACEs, respondents reporting four or more ACEs had over four times the odds of Alcohol or Drug Use, Mental Illness, Depression, and/or Anxiety outcomes and more than twice the odds of diabetes, hypertension, obesity, and/or smoking outcomes. CONCLUSION: Findings from this analysis underscore the potential benefit of providing focused preventative approaches to mitigating ACEs in KSA in relation to both the specific and cumulative burden of health and risky behavior outcomes. PMID- 27662615 TI - Drosophila TDP-43 RNA-Binding Protein Facilitates Association of Sister Chromatid Cohesion Proteins with Genes, Enhancers and Polycomb Response Elements. AB - The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes. It is unknown why some active genes bind high levels of cohesin and some do not. Here we show that the TBPH and Lark RNA-binding proteins influence association of Nipped-B and cohesin with genes and gene regulatory sequences. In vitro, TBPH and Lark proteins specifically bind RNAs produced by genes occupied by Nipped-B and cohesin. By genomic chromatin immunoprecipitation these RNA-binding proteins also bind to chromosomes at cohesin-binding genes, enhancers, and Polycomb response elements (PREs). RNAi depletion reveals that TBPH facilitates association of Nipped-B and cohesin with genes and regulatory sequences. Lark reduces binding of Nipped-B and cohesin at many promoters and aids their association with several large enhancers. Conversely, Nipped-B facilitates TBPH and Lark association with genes and regulatory sequences, and interacts with TBPH and Lark in affinity chromatography and immunoprecipitation experiments. Blocking transcription does not ablate binding of Nipped-B and the RNA-binding proteins to chromosomes, indicating transcription is not required to maintain binding once established. These findings demonstrate that RNA-binding proteins help govern association of sister chromatid cohesion proteins with genes and enhancers. PMID- 27662617 TI - The Value of Median Nerve Sonography as a Predictor for Short- and Long-Term Clinical Outcomes in Patients with Carpal Tunnel Syndrome: A Prospective Long Term Follow-Up Study. AB - OBJECTIVES: To investigate the prognostic value of B-mode and Power Doppler (PD) ultrasound of the median nerve for the short- and long-term clinical outcomes of patients with carpal tunnel syndrome (CTS). METHODS: Prospective study of 135 patients with suspected CTS seen 3 times: at baseline, then at short-term (3 months) and long-term (15-36 months) follow-up. At baseline, the cross-sectional area (CSA) of the median nerve was measured with ultrasound at 4 levels on the forearm and wrist. PD signals were graded semi-quantitatively (0-3). Clinical outcomes were evaluated at each visit with the Boston Questionnaire (BQ) and the DASH Questionnaire, as well as visual analogue scales for the patient's assessment of pain (painVAS) and physician's global assessment (physVAS). The predictive values of baseline CSA and PD for clinical outcomes were determined with multivariate logistic regression models. RESULTS: Short-term and long-term follow-up data were available for 111 (82.2%) and 105 (77.8%) patients, respectively. There was a final diagnosis of CTS in 84 patients (125 wrists). Regression analysis revealed that the CSA, measured at the carpal tunnel inlet, predicted short-term clinical improvement according to BQ in CTS patients undergoing carpal tunnel surgery (OR 1.8, p = 0.05), but not in patients treated conservatively. Neither CSA nor PD assessments predicted short-term improvement of painVAS, physVAS or DASH, nor was any of the ultrasound parameters useful for the prediction of long-term clinical outcomes. CONCLUSIONS: Ultrasound assessment of the median nerve at the carpal tunnel inlet may predict short-term clinical improvement in CTS patients undergoing carpal tunnel release, but long-term outcomes are unrelated to ultrasound findings. PMID- 27662616 TI - Prognostic factors of overall survival in children and adolescents enrolled in dose-finding trials in Europe: An Innovative Therapies for Children with Cancer study. AB - OBJECTIVES: Dose-finding trials are fundamental to develop novel drugs for children and adolescents with advanced cancer. It is crucial to maximise individual benefit, whilst ensuring adequate assessment of key study end-points. We assessed prognostic factors of survival in paediatric phase I trials, including two predictive scores validated in adult oncology: the Royal Marsden Hospital (RMH) and the MD Anderson Cancer Center (MDACC) scores. METHODS: Data of patients with solid tumours aged <18 years at enrolment in their first dose finding trial between 2000 and 2014 at eight centres of the Innovative Therapies for Children with Cancer European consortium were collected. Survival distributions were compared using log-rank test and Cox regression analyses. RESULTS: Overall, 248 patients were evaluated: median age, 11.2 years (range 1.0 17.9); 46% had central nervous system (CNS) tumours and 54% extra-CNS tumours. Complete responses were observed in 2.1%, partial responses in 7.2% and stable disease in 25.9%. Median overall survival (OS) was 6.3 months (95% confidence interval, 5.2-7.4). Lansky/Karnofsky <=80%, no school/work attendance, elevated creatinine and RMH score >=1 correlated with worse OS in the multivariate analysis. The RMH and MDACC scores correlated with OS in adolescents (12-17 years), p = 0.002, but not in children (2-11 years). CONCLUSIONS: Performance status of 90-100% and school/work attendance at enrolment are strong indicators of longer OS in paediatric phase I trials. Adult predictive scores correlate with survival in adolescents. These findings provide a useful orientation about potential prognosis and could lead in the future to more paediatric-adapted eligibility criteria in early-phase trials. PMID- 27662619 TI - Long Noncoding RNA CPS1-IT1 Suppresses Cell Proliferation and Metastasis in Human Lung Cancer. AB - The long noncoding CPS1 intronic transcript 1 (lncRNA CPS1-IT1) is a recently identified tumor suppressor in the lncRNA family of proteins. Whether this lncRNA plays any functional role in solid tumors remains largely unknown. The present study aimed to investigate the role of lncRNA CPS1-IT1 in human lung cancer. Expression of lncRNA CPS1-IT1 was initially assessed in human lung cancer and in a series of lung cancer cell lines. The effects of CPS1-IT1 overexpression on cell proliferation, migration, and invasion were examined in lung cancer cell lines A549 and 95D. It was found that lncRNA CPS1-IT1 was significantly lower in cancerous tissues than in noncancerous tissues. lncRNA CPS1-IT1 was differentially expressed in lung cancer cell lines and expressed the least in two highly invasive cell lines, A549 and 95D. Overexpression of CPS1-IT1 slowed down cell proliferation by 35.7% in A549 cells and 30.8% in 95D cells on the fifth day. Cell migration was inhibited by 59% in A549 cells and 48% in 95D cells, and cell invasion was suppressed by 60% in both cell lines after overexpression of CPS1-IT1. While cell apoptosis was induced, CPS1-IT1 overexpression promoted the activities of caspase 3 and caspase 9 without affecting that of caspase 8. These observations were suggestive of the tumor-suppressive role of lncRNA CPS1-IT1 in lung cancer. Our data suggest that CPS1-IT1 may be used as a biomarker for early diagnosis and therapeutic targets against lncRNA and may be promising in the treatment of lung cancer. PMID- 27662618 TI - Indirect CT Venography at 80 kVp with Sinogram-Affirmed Iterative Reconstruction Compared to 120 kVp with Filtered Back Projection: Assessment of Image Quality and Radiation Dose. AB - OBJECTIVE: To evaluate the image quality and radiation dose of indirect computed tomographic venography (CTV) using 80 kVp with sinogram-affirmed iterative reconstruction (SAFIRE) and 120 kVp with filtered back projection (FBP). MATERIALS AND METHODS: This retrospective study was approved by our institution and informed consent was waived. Sixty-one consecutive patients (M: F = 27: 34, mean age 60 +/- 16, mean BMI 23.6 +/- 3.6 kg/m2) underwent pelvic and lower extremity CTVs [group A (n = 31, 120 kVp, reconstructed with FBP) vs. group B (n = 30, 80 kVp, reconstructed with SAFIRE)]. The vascular enhancement, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared. Subjective image analysis for image quality and noise was performed by two radiologists. Radiation dose was compared between the two groups. RESULTS: Compared with group A, higher mean vascular enhancement was observed in the group B (group A vs. B, 118.8 +/- 15.7 HU vs. 178.6 +/- 39.6 HU, p < 0.001), as well as image noise (12.0 +/- 3.8 HU vs. 17.9 +/- 6.1 HU, p < 0.001) and CNR (5.1 +/- 1.9 vs. 7.6 +/- 3.0, p < 0.001). The SNRs were not significantly different in both groups (11.2 +/- 4.8 vs. 10.8 +/- 3.7, p = 0.617). There was no significant difference in subjective image quality between the two groups (all p > 0.05). The subjective image noise was higher in the group B (p = 0.036 in reader 1, p = 0.005 in reader 2). The inter-observer reliability for assessing subjective image quality was good (ICC 0.746~0.784, p < 0.001). The mean CT dose index volume (CTDIvol) and mean dose length product (DLP) were significantly lower in group B than group A [CTDIvol, 6.4 +/- 1.3 vs. 2.2 +/- 2.2 mGy (p < 0.001); DLP, 499.1 +/ 116.0 vs. 133.1 +/- 45.7 mGy * cm (p < 0.001)]. CONCLUSIONS: CTV using 80 kVp combined with SAFIRE provides lower radiation dose and improved CNR compared to CTV using 120 kVp with FBP. PMID- 27662620 TI - Metabolic Profiling of Intact Arabidopsis thaliana Leaves during Circadian Cycle Using 1H High Resolution Magic Angle Spinning NMR. AB - Arabidopsis thaliana is the most widely used model organism for research in plant biology. While significant advances in understanding plant growth and development have been made by focusing on the molecular genetics of Arabidopsis, extracting and understanding the functional framework of metabolism is challenging, both from a technical perspective due to losses and modification during extraction of metabolites from the leaves, and from the biological perspective, due to random variation obscuring how well the function is performed. The purpose of this work is to establish the in vivo metabolic profile directly from the Arabidopsis thaliana leaves without metabolite extraction, to reduce the complexity of the results by multivariate analysis, and to unravel the mitigation of cellular complexity by predominant functional periodicity. To achieve this, we use the circadian cycle that strongly influences metabolic and physiological processes and exerts control over the photosynthetic machinery. High resolution-magic angle spinning nuclear magnetic resonance (HR-MAS NMR) was applied to obtain the metabolic profile directly from intact Arabidopsis leaves. Combining one- and two dimensional 1H HR-MAS NMR allowed the identification of several metabolites including sugars and amino acids in intact leaves. Multivariate analysis on HR MAS NMR spectra of leaves throughout the circadian cycle revealed modules of primary metabolites with significant and consistent variations of their molecular components at different time points of the circadian cycle. Since robust photosynthetic performance in plants relies on the functional periodicity of the circadian rhythm, our results show that HR-MAS NMR promises to be an important non-invasive method that can be used for metabolomics of the Arabidopsis thaliana mutants with altered physiology and photosynthetic efficiency. PMID- 27662621 TI - Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-gamma Production. AB - : Using a unique resource of samples from a controlled human malaria infection (CHMI) study, we identified a novel population of CD4+ T cells whose frequency in the peripheral blood was inversely correlated with parasite burden following P. falciparum infection. These CD4+ T cells expressed the multifunctional ectoenzyme CD38 and had unique features that distinguished them from other CD4+ T cells. Specifically, their phenotype was associated with proliferation, activation and cytotoxic potential as well as significantly impaired production of IFN-gamma and other cytokines and reduced basal levels of activated STAT1. A CD38+ CD4+ T cell population with similar features was identified in healthy uninfected individuals, at lower frequency. CD38+ CD4+ T cells could be generated in vitro from CD38- CD4+ T cells after antigenic or mitogenic stimulation. This is the first report of a population of CD38+ CD4+ T cells with a cytotoxic phenotype and markedly impaired IFN-gamma capacity in humans. The expansion of this CD38+ CD4+ T population following infection and its significant association with reduced blood-stage parasite burden is consistent with an important functional role for these cells in protective immunity to malaria in humans. Their ubiquitous presence in humans suggests that they may have a broad role in host-pathogen defense. TRIAL REGISTRATION: ClinicalTrials.gov clinical trial numbers ACTRN12612000814875, ACTRN12613000565741 and ACTRN12613001040752. PMID- 27662623 TI - Role and therapeutic potential of CDK12 in human cancers. AB - Phosphorylation of the RNA polymerase II C-terminal domain by cyclin-dependent kinases (CDKs) is important for productive transcription. Deregulated transcription-CDKs have been reported in different human cancers. Until recently CDK9 was the only transcription-CDK with a causative role in cancer, but evidence is cumulating of the importance of CDK12. This review summarizes the role of CDK12 in transcription and RNA processing, in maintaining genomic stability/integrity and in tumorigenesis. CDK12 mutations have been reported in many cancers and have been suggested as a cause of defective DNA repair in ovarian carcinoma. CDK12 may have a role as a new therapeutic target in oncology. PMID- 27662622 TI - Variation in Lingual Nerve Course: A Human Cadaveric Study. AB - The lingual nerve is a terminal branch of the mandibular nerve. It is varied in its course and in its relationship to the mandibular alveolar crest, submandibular duct and also the related muscles in the floor of the mouth. This study aims to understand the course of the lingual nerve from the molar area until its insertion into the tongue muscle. This cadaveric research involved the study of 14 hemi-mandibles and consisted of two parts: (i) obtaining morphometrical measurements of the lingual nerve to three landmarks on the alveolar ridge, and (b) understanding non-metrical or morphological appearance of its terminal branches inserting in the ventral surface of the tongue. The mean distance between the fourteen lingual nerves and the alveolar ridge was 12.36 mm, and they were located 12.03 mm from the lower border of the mandible. These distances were varied when near the first molar (M1), second molar (M2) and third molar (M3). The lingual nerve coursed on the floor of the mouth for approximately 25.43 mm before it deviated toward the tongue anywhere between the mesial of M1 and distal of M2. Thirteen lingual nerves were found to loop around the submandibular duct for an average distance of 6.92 mm (95% CI: 5.24 to 8.60 mm). Their looping occurred anywhere between the M2 and M3. In 76.9% of the cases the loop started around the M3 region and the majority (69.2%) of these looping ended at between the first and second molars and at the lingual developmental groove of the second molar. It gave out as many as 4 branches at its terminal end at the ventral surface of the tongue, with the presence of 2 branches being the most common pattern. An awareness of the variations of the lingual nerve is important to prevent any untoward complications or nerve injury and it is hoped that these findings will be useful for planning of surgical procedures related to the alveolar crest, submandibular gland/ duct and surrounding areas. PMID- 27662625 TI - The effect of collagen fibril orientation on the biphasic mechanics of articular cartilage. AB - The highly inhomogeneous distribution of collagen fibrils may have important effects on the biphasic mechanics of articular cartilage. However, the effect of the inhomogeneity of collagen fibrils has mainly been investigated using simplified three-layered models, which may have underestimated the effect of collagen fibrils by neglecting their realistic orientation. The aim of this study was to investigate the effect of the realistic orientation of collagen fibrils on the biphasic mechanics of articular cartilage. Five biphasic material models, each of which included a different level of complexity of fibril reinforcement, were solved using two different finite element software packages (Abaqus and FEBio). Model 1 considered the realistic orientation of fibrils, which was derived from diffusion tensor magnetic resonance images. The simplified three layered orientation was used for Model 2. Models 3-5 were three control models. The realistic collagen orientations obtained in this study were consistent with the literature. Results from the two finite element implementations were in agreement for each of the conditions modelled. The comparison between the control models confirmed some functions of collagen fibrils. The comparison between Models 1 and 2 showed that the widely-used three-layered inhomogeneous model can produce similar fluid load support to the model including the realistic fibril orientation; however, an accurate prediction of the other mechanical parameters requires the inclusion of the realistic orientation of collagen fibrils. PMID- 27662624 TI - Association between Density of Coronary Artery Calcification and Serum Magnesium Levels among Patients with Chronic Kidney Disease. AB - BACKGROUND: The Agatston score, commonly used to quantify coronary artery calcification (CAC), is determined by the plaque area and density. Despite an excellent predictability of the Agatston score for cardiovascular events, the density of CAC has never been studied in patients with pre-dialysis chronic kidney disease (CKD). This study aimed to analyze the CAC density and its association with serum mineral levels in CKD. METHODS: We enrolled patients with pre-dialysis CKD who had diabetes mellitus, prior cardiovascular disease history, elevated low-density lipoprotein cholesterol levels, or smoking history. The average CAC density was calculated by dividing the Agatston score by the total area of CAC. RESULTS: The mean estimated glomerular filtration rate (eGFR) of 109 enrolled patients was 35.7 mL/min/1.73 m2. The correlation of the Agatston score with density was much weaker than that with the total area (R2 = 0.19, P < 0.001; and R2 = 0.99, P < 0.001, respectively). Multivariate analyses showed that serum magnesium level was inversely associated with the density, but not with the total area, after adjustment for demographics and clinical factors related to malnutrition-inflammation-atherosclerosis syndrome and mineral and bone disorders including fibroblast growth factor 23 (P = 0.006). This inverse association was pronounced among patients with higher serum phosphate levels (P for interaction = 0.02). CONCLUSION: CAC density was inversely associated with serum magnesium levels, particularly in patients with higher serum phosphate levels. PMID- 27662626 TI - Critical Role of IRF-3 in the Direct Regulation of dsRNA-Induced Retinoic Acid Inducible Gene-I (RIG-I) Expression. AB - The cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I), which is also known as an IFN-stimulated gene (ISG), senses viral RNA to activate antiviral signaling. It is therefore thought that RIG-I is regulated in a STAT1 dependent manner. Although RIG-I-mediated antiviral signaling is indispensable for the induction of an appropriate adaptive immune response, the mechanism underlying the regulation of RIG-I expression remains elusive. Here, we examined the direct regulation of RIG-I expression by interferon regulatory factor 3 (IRF 3), which is an essential molecule for antiviral innate immunity. We initially found that RIG-I can be induced by dsRNA in both IFN-independent and IRF-3 dependent manners. A sequence analysis revealed that the RIG-I gene has putative IRF-3-binding sites in its promoter region. Using a combination of cellular, molecular biological, and mutational approaches, we first showed that IRF-3 can directly regulate the expression of RIG-I via a single IRF-element (IRF-E) site in the proximal promoter region of the RIG-I gene in response to dsRNA. IRF-3 is considered a master regulator in antiviral signaling for the generation of type I interferons (IFNs). Thus, our findings demonstrate that RIG-I expression induced by the IRF-3-mediated pathway may serve as a crucial antiviral factor for reinforcing a surveillance system against viral invasion through the regulation of the cytoplasmic viral sensor RIG-I. PMID- 27662627 TI - Arachidonic Acid Metabolite 19(S)-HETE Induces Vasorelaxation and Platelet Inhibition by Activating Prostacyclin (IP) Receptor. AB - 19(S)-hydroxy-eicosatetraenoic acid (19(S)-HETE) belongs to a family of arachidonic acid metabolites produced by cytochrome P450 enzymes, which play critical roles in the regulation of cardiovascular, renal and pulmonary functions. Although it has been known for a long time that 19(S)-HETE has vascular effects, its mechanism of action has remained unclear. In this study we show that 19(S)-HETE induces cAMP accumulation in the human megakaryoblastic leukemia cell line MEG-01. This effect was concentration-dependent with an EC50 of 520 nM, insensitive to pharmacological inhibition of COX-1/2 and required the expression of the G-protein Gs. Systematic siRNA-mediated knock-down of each G protein coupled receptor (GPCR) expressed in MEG-01 followed by functional analysis identified the prostacyclin receptor (IP) as the mediator of the effects of 19(S)-HETE, and the heterologously expressed IP receptor was also activated by 19(S)-HETE in a concentration-dependent manner with an EC50 of 567 nM. Pretreatment of isolated murine platelets with 19(S)-HETE blocked thrombin induced platelets aggregation, an effect not seen in platelets from mice lacking the IP receptor. Furthermore, 19(S)-HETE was able to relax mouse mesenteric artery- and thoracic aorta-derived vessel segments. While pharmacological inhibition of COX-1/2 enzymes had no effect on the vasodilatory activity of 19(S) HETE these effects were not observed in vessels from mice lacking the IP receptor. These results identify a novel mechanism of action for the CYP450 dependent arachidonic acid metabolite 19(S)-HETE and point to the existence of a broader spectrum of naturally occurring prostanoid receptor agonists. PMID- 27662629 TI - Mucosal and lacrimal flaps for endonasal dacryocystorhinostomy: a systematic review. AB - BACKGROUND: Historically dacryocystorhinostomy (DCR) has been performed externally with very good outcomes. Current literature shows comparable success rates between endonasal and external approaches. A common reason for the failure of a DCR is the reclosure of the nasolacrimal stoma by granulation tissue and synechiae. OBJECTIVE OF REVIEW: A systematic review and critical evaluation of the evidence relating to the preservation of nasal mucosal flaps in DCR surgery. TYPE OF REVIEW AND EVALUATION METHOD: A systematic review using the consort guidance for review of randomised control trials. SEARCH STRATEGY: A search of the following evidence-based medicine databases was performed: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials, Ovid, Medline, EMBASE and PubMed. The search was limited to English language articles, and the following key words were used: Endonasal, Endoscopic, Dacryocystorhinostomy, DCR, Mucosal Flaps, between years 1970 and 2015. RESULTS: The best available evidence was level 1B, comprising two randomised control trials and three comparative studies included in the review. The main outcome measures used were lacrimal irrigation and absence of epiphora. Two of the studies demonstrated a statistically significant benefit of mucosal sparing either with nasal mucosal flaps or with lacrimal flaps. More debridement was needed, and granulation tissue was also seen in the groups without mucosal preservation. There was no difference in surgical complications between a mucosal and non-mucosal-sparing technique. CONCLUSIONS: The overall quality of current evidence is poor, and there does however appear to be a trend towards improved outcomes and reduced granulation in groups where nasal mucosal and lacrimal flaps were preserved, but this is not clear-cut. There was no evidence of increased complication rates with mucosal-sparing techniques. We recommend that until further good quality research is available we should be performing a mucosal-sparing technique when performing DCR routinely. PMID- 27662628 TI - Supramolecular Hemicage Cobalt Mediators for Dye-Sensitized Solar Cells. AB - A new class of dye-sensitized solar cells (DSSCs) using the hemicage cobalt-based mediator [Co(ttb)]2+/3+ with the highly preorganized hexadentate ligand 5,5'',5''''-((2,4,6-triethyl benzene-1,3,5-triyl)tris(ethane-2,1-diyl))tri-2,2' bipyridine (ttb) has been fully investigated. The performances of DSSCs sensitized with organic D-pi-A dyes utilizing either [Co(ttb)]2+/3+ or the conventional [Co(bpy)3 ]2+/3+ (bpy=2,2'-bipyridine) redox mediator are comparable under 1000 W m-2 AM 1.5 G illumination. However, the hemicage complexes exhibit exceptional stability under thermal and light stress. In particular, a 120-hour continuous light illumination stability test for DSSCs using [Co(ttb)]2+/3+ resulted in a 10 % increase in the performance, whereas a 40 % decrease in performance was found for [Co(bpy)3 ]2+/3+ electrolyte-based DSSCs under the same conditions. These results demonstrate the great promise of [Co(ttb)]2+/3+ complexes as redox mediators for efficient, cost-effective, large-scale DSSC devices. PMID- 27662630 TI - Pathways of root uptake and membrane transport of Cd2+ in the zinc/cadmium hyperaccumulating plant Sedum plumbizincicola. AB - Uptake and membrane transport of cadmium (Cd) in roots of the hyperaccumulator Sedum plumbizincicola X.H. Guo et S.B. Zhou ex L.H. Wu was characterized by assessing the impact of various inhibitors and ion channel blockers on Cd accumulation as well as the real-time net Cd2+ flux at the roots with application of the scanning ion-selective electrode technique. The uncouplers 2,4 dinitrophenol and P-type adenosine triphosphatase inhibitor Na3 VO4 significantly limited Cd2+ uptake and transport kinetics in the root of S. plumbizincicola. These findings indicate that Cd is actively taken up into the roots. The Cd content in plant was significantly decreased with pretreatments of the Ca2+ channel blocker La3+ or Gd3+ and the K+ channel blocker tetraethylammonium, as well as in the presence of higher concentration of Ca2+ and K+ . These findings indicated that uptake of Cd2+ into the root of S. plumbizincicola proceeds through ion channels that are permeable to both Ca2+ and K+ as confirmed by the direct evidence of real-time net Cd2+ fluxes at the root surface in the treatments with ion channel inhibitors, as well as in the presence of elevated concentrations of Ca2+ and K+ . In addition, the results suggested a role for phytochelatin and protein synthesis in mediating Cd2+ uptake by S. plumbizincicola. These findings increase the understanding of Cd2+ uptake and membrane transport pathways in roots of the Zn/Cd hyperaccumulator S. plumbizincicola. Environ Toxicol Chem 2017;36:1038-1046. (c) 2016 SETAC. PMID- 27662631 TI - Differences in Activation of HIV-1 Replication by Superinfection With HIV-1 and HIV-2 in U1 Cells. AB - Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir that serve as a viral source for the infection of CD4 T cells. The relationship between HIV-1 latent infection and superinfection in macrophages has not been well studied. Using susceptible U1 cells chronically infected with HIV-1, we studied the effects of HIV superinfection on latency and differences in superinfection with HIV-1 and HIV-2 in macrophages. We found that HIV-1 (MN) superinfection displayed increased HIV-1 replication in a time-dependent manner; while cells infected with HIV-2 (Rod) initially showed increased HIV-1 replication, followed by a decrease in HIV-1 RNA production. HIV-1 superinfection upregulated/activated NF-KB, NFAT, AP-1, SP-1, and MAPK Erk through expression/activation of molecules, CD4, CD3, TCRbeta, Zap-70, PLCgamma1, and PKCTheta in T cell receptor-related signaling pathways; while HIV-2 superinfection initially increased expression/activation of these molecules followed by decreased protein expression/activation. HIV superinfection initially downregulated HDAC1 and upregulated acetyl-histone H3 and histone H3 (K4), while HIV-2 superinfection demonstrated an increase in HDAC1 and a decrease in acetyl histone H3 and histone H3 (K4) relative to HIV-1 superinfection. U1 cells superinfected with HIV-1 or HIV-2 showed differential expression of proteins, IL 2, PARP-1, YB-1, and LysRS. These findings indicate that superinfection with HIV 1 or HIV-2 has different effects on reactivation of HIV-1 replication. HIV-1 superinfection with high load of viral replication may result in high levels of cytotoxicity relative to HIV-2 superinfection. Cells infected with HIV-2 showed lower level of HIV-1 replication, suggesting that co-infection with HIV-2 may result in slower progression toward AIDS. J. Cell. Physiol. 232: 1746-1753, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27662632 TI - Impact of stent diameter and length on in-stent restenosis after DES vs BMS implantation in patients needing large coronary stents-A clinical and health economic evaluation. AB - AIMS: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. METHODS/RESULTS: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (>=3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and <=15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. CONCLUSION: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents >=3.0 mm and <=15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length. PMID- 27662633 TI - Radionuclide Assessment of Cardiac Function and Dyssynchrony in Children with Idiopathic Ventricular Tachycardia. AB - BACKGROUND: The aim of the study was to evaluate the impact of idiopathic ventricular tachycardia and premature ventricular beats on cardiac function and dyssynchrony and to elucidate relationships between data of scintigraphic and intracardiac electrophysiology studies (EPSs). METHODS: The study comprised 64 patients with idiopathic ventricular arrhythmias (VAs; median age of 14 years ranging from 8 to 18 years). The control group comprised 20 patients (median age of 12 ranging from 7 to 16 years) without cardiac arrhythmias. EPS and radiofrequency ablation (RFA) procedure for VA were performed in 21 children according to indications. The functional state of both ventricles was assessed by gated blood pool single photon emission computer tomography (GBP-SPECT) before and after RFA in all patients. RESULTS: Patients with VA had local areas of asynchronous myocardial contraction (AMC). Compared with the control group, VA patients had significantly higher values of end-diastolic volume, end-systolic volume, and lower contractility indices. Negative association was found between total numbers of AMC areas and cardiac contractility indices. Ectopic foci localization, determined based on EPS data, was associated with AMC areas topography based on GBP-SPECT. RFA procedure significantly improved cardiac contractility indices; AMC areas completely disappeared or decreased compared with the preoperative conditions. CONCLUSION: In VA patients, AMC areas were localized mostly in the right ventricle. Comparison of the results of GBP-SPECT and EPS studies showed a relationship between AMC localizations and ectopic foci topography. The fact that AMC areas disappeared after RFA supports the hypothesis stating that the presence of AMC areas is a scintigraphic symptom of ectopic focus. PMID- 27662634 TI - Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations. AB - Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2 ug/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3 ug/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations for reporting caffeine and theophylline are still lacking. The aim of the study was to investigate IRLs for theobromine in blood and for caffeine and theophylline in blood and urine. Therefore, a set of six administrations were carried out including both single i.v. and single oral administrations of caffeine, theobromine and theophylline. Plasma and urine concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Applying the Toutain model approach an effective plasma concentration (EPC) of caffeine was estimated at 3.05 ug/mL, irrelevant concentrations in blood (IPC) and urine (IUC) approached 6 and 12 ng/mL, respectively. EPC of theobromine was calculated with 3.80 ug/mL, and irrelevant concentrations of theobromine were determined at 8 ng/mL in plasma and at 142 ng/mL in urine. Toutain modelling of the theophylline data produced an EPC, IPC, and IUC of 3.20 ug/mL, 6 ng/mL, and 75 ng/mL, respectively. The obtained irrelevant concentrations were used to postulate IRLs for theobromine in plasma and for caffeine and theophylline in plasma and urine. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27662635 TI - Interactions between parental traits, environmental harshness and growth rate in determining telomere length in wild juvenile salmon. AB - A larger body size confers many benefits, such as increased reproductive success, ability to evade predators and increased competitive ability and social status. However, individuals rarely maximize their growth rates, suggesting that this carries costs. One such cost could be faster attrition of the telomeres that cap the ends of eukaryotic chromosomes and play an important role in chromosome protection. A relatively short telomere length is indicative of poor biological state, including poorer tissue and organ performance, reduced potential longevity and increased disease susceptibility. Telomere loss during growth may also be accelerated by environmental factors, but these have rarely been subjected to experimental manipulation in the natural environment. Using a wild system involving experimental manipulations of juvenile Atlantic salmon Salmo salar in Scottish streams, we found that telomere length in juvenile fish was influenced by parental traits and by direct environmental effects. We found that faster growing fish had shorter telomeres and there was a greater cost (in terms of reduced telomere length) if the growth occurred in a harsher environment. We also found a positive association between offspring telomere length and the growth history of their fathers (but not mothers), represented by the number of years fathers had spent at sea. This suggests that there may be long-term consequences of growth conditions and parental life history for individual longevity. PMID- 27662636 TI - The effects of irradiation on the biological and biomechanical properties of an acellular porcine superflexor tendon graft for cruciate ligament repair. AB - Acellular xenogeneic tissues have the potential to provide 'off-the-shelf' grafts for anterior cruciate ligament (ACL) repair. To ensure that such grafts are sterile following packaging, it is desirable to use terminal sterilization methods. Here, the effects of gamma and electron beam irradiation on the biological and biomechanical properties of a previously developed acellular porcine superflexor tendon (pSFT) were investigated. Irradiation following treatment with peracetic acid was compared to peracetic acid treatment alone and the stability of grafts following long-term storage assessed. Irradiation did not affect total collagen content or biocompatibility (determined using a contact cytotoxicity assay) of the grafts, but slightly increased the amount of denatured collagen in and decreased the thermal denaturation temperature of the tissue in a dose dependant fashion. Biomechanical properties of the grafts were altered by irradiation (reduced ultimate tensile strength and Young's modulus, increased failure strain), but remained superior to reported properties of the native human ACL. Long term storage at 4 degrees C had no negative effects on the grafts. Of all the conditions tested, a dose of minimum 25 kGy of gamma irradiation had least effect on the grafts, suggesting that this dose produces a biocompatible pSFT graft with adequate mechanical properties for ACL repair. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2477-2486, 2017. PMID- 27662638 TI - Protein Staining Agents from Cationic and Neutral Luminescent Iridium(III) Complexes. AB - Seven luminescent iridium(III) complexes were prepared to investigate the relationships between chemical structures and properties of protein staining. For the first time, the effect of the main ligand, the pi conjugation effect of the ancillary ligand, and the charge effect of organometallic complexes on protein staining has been revealed. Most importantly, this study gives the first experimental evidence of the potential applications of charge-neutral organometallic complexes in protein staining, which could open an avenue of exploiting novel protein staining agents in the future. PMID- 27662637 TI - Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection. AB - Vascular dementia (VaD), considered the second most common cause of cognitive impairment after Alzheimer disease in the elderly, involves the impairment of memory and cognitive function as a consequence of cerebrovascular disease. Chronic cerebral hypoperfusion is a common pathophysiological condition frequently occurring in VaD. It is generally associated with neurovascular degeneration, in which neuronal damage and blood-brain barrier alterations coexist and evoke beta-amyloid-induced oxidative and nitrosative stress, mitochondrial dysfunction, and inflammasome- promoted neuroinflammation, which contribute to and exacerbate the course of disease. Vascular cognitive impairment comprises a heterogeneous group of cognitive disorders of various severity and types that share a presumed vascular etiology. The present study reviews major pathogenic factors involved in VaD, highlighting the relevance of cerebrocellular stress and hormetic responses to neurovascular insult, and addresses these mechanisms as potentially viable and valuable as foci of novel neuroprotective methods to mitigate or prevent VaD. (c) 2016 Wiley Periodicals, Inc. PMID- 27662639 TI - Genetic basis for rapidly evolved tolerance in the wild: adaptation to toxic pollutants by an estuarine fish species. AB - Atlantic killifish (Fundulus heteroclitus) residing in some urban and industrialized estuaries of the US eastern seaboard demonstrate recently evolved and extreme tolerance to toxic aryl hydrocarbon pollutants, characterized as dioxin-like compounds (DLCs). Here, we provide an unusually comprehensive accounting (69%) through quantitative trait locus (QTL) analysis of the genetic basis for DLC tolerance in killifish inhabiting an urban estuary contaminated with PCB congeners, the most toxic of which are DLCs. Consistent with mechanistic knowledge of DLC toxicity in fish and other vertebrates, the aryl hydrocarbon receptor (ahr2) region accounts for 17% of trait variation; however, QTL on independent linkage groups and their interactions have even greater explanatory power (44%). QTL interpreted within the context of recently available Fundulus genomic resources and shared synteny among fish species suggest adaptation via interacting components of a complex stress response network. Some QTL were also enriched in other killifish populations characterized as DLC-tolerant and residing in distant urban estuaries contaminated with unique mixtures of pollutants. Together, our results suggest that DLC tolerance in killifish represents an emerging example of parallel contemporary evolution that has been driven by intense human-mediated selection on natural populations. PMID- 27662640 TI - Comparison of diagnostic accuracies of two- and three-dimensional MR elastography of the liver. AB - PURPOSE: To evaluate the effect of imaging sequence (spin-echo echo-planar imaging [EPI] and gradient-echo [GRE]) and postprocessing method (two-dimensional [2D] and 3D inversion algorithms) on liver MR elastography (MRE) and to validate the diagnostic performance of EPI-MRE3D versus conventional GRE-MRE2D for liver fibrosis staging. MATERIALS AND METHODS: Three MRE methods (EPI-MRE3D , EPI-MRE2D , and GRE-MRE2D ) were performed on soft and mildly stiff phantoms and 58 patients with chronic liver disease using a 3 Tesla clinical MRI scanner, and stiffness values were compared among the three methods. A validation study comprised 73 patients with histological liver fibrosis (F0-4, METAVIR system). Areas under the receiver operating characteristic curves (AUCs) and accuracies for diagnosing significant fibrosis (F3-4) and cirrhosis (F4) were compared between EPI-MRE3D and GRE-MRE2D . RESULTS: Stiffness values of the soft and mildly stiff phantoms were 2.4 kPa and 4.0 kPa by EPI-MRE3D ; 2.6 kPa and 4.2 kPa by EPI-MRE2D ; and 2.7 kPa and 4.2 kPa by GRE-MRE2D . In patients, EPI-MRE3D provided significantly lower stiffness values than other methods (P < 0.001). However, there was no significant difference between GRE-MRE2D and EPI-MRE2D (P = 0.12). The AUCs and accuracies of EPI-MRE3D and GRE-MRE2D were statistically equivalent in the diagnoses of significant fibrosis (F3-4) and cirrhosis (F4) (all P < 0.005). CONCLUSION: EPI-MRE3D showed modestly lower liver stiffness values than conventional GRE-MRE2D . The diagnostic performances of EPI-MRE3D and GRE-MRE2D were equivalent for liver fibrosis staging. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:1163-1170. PMID- 27662643 TI - Prenatal screening for microcephaly: an update after three decades. AB - BACKGROUND: Due to the recent outbreak of Zika virus, there has been a newfound interest in fetal and neonatal microcephaly. In 1984, Chervenak et al. proposed criteria for the prenatal ultrasound diagnosis of microcephaly as <=3 standard deviations (SD) from the mean. Despite improvements in medicine these criteria have not been reevaluated in 30 years. OBJECTIVE: To examine how the original 1984 Chervenak et al. criteria for the diagnosis of fetal microcephaly apply to a current population utilizing modern ultrasound equipment and techniques. STUDY DESIGN: Retrospective database review of 27,697 ultrasound exams between 18 and 40 weeks' gestation. Mean and SDs were calculated for each week of gestation from 18 to 40 completed weeks and these were compared to the 1984 data. RESULTS: There is no statistically significant difference in gestational age-specific mean head circumference (HC) between the two studied populations. Because the current dataset is larger the SD differ. CONCLUSIONS: The 1984 ultrasound criteria for microcephaly remain valid. Physicians today have two alternatives: either use the 3SD cutoff as recommended by Chervenak et al. and endorsed by the Society for Maternal-Fetal Medicine (SMFM) or develop a new dataset for one's population with statistical validation. PMID- 27662641 TI - Reduced feeding tube duration with intensity-modulated radiation therapy for head and neck cancer: A Surveillance, Epidemiology, and End Results-Medicare Analysis. AB - BACKGROUND: Intensity-modulated radiation therapy (IMRT) is a technologically advanced and resource-intensive method of delivering radiation therapy (RT) and is used to minimize toxicity for patients with head and neck cancer (HNC). Dependence on feeding tubes is a significant marker of toxicity of RT. The objective of this analysis was to compare the placement and duration of feeding tube use among patients with HNC from 1999 through 2011. METHODS: The cohort, demographics, and cancer-related variables were determined using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, and claims data were used to analyze treatment details. RESULTS: In total, 2993 patients were identified. At a median follow-up of 47 months, 54.4% of patients had ever had a feeding tube placed. The median duration from feeding tube placement to removal was 277 days. On zero-inflated negative binomial regression, patients who received IMRT and 3-dimensional RT (3DRT) (non-IMRT) had similar rates of feeding tube placement (odds ratio, 1.10; P = .35); however, patients who received 3DRT had a feeding tube in place 1.18 times longer than those who received IMRT (P = .03). The difference was only observed among patients who received definitive RT; patients who underwent surgery and also received adjuvant RT had no statistically significant difference in feeding tube placement or duration. CONCLUSIONS: Patients with HNC who received definitive IMRT had a significantly shorter duration of feeding tube placement than those who received 3DRT. These data suggest that there may be significant quality-of-life benefits to IMRT with respect to long-term swallowing function in patients with HNC. Cancer 2017;123:283-293. (c) 2016 American Cancer Society. PMID- 27662642 TI - Sperm Binding to Oviduct Epithelial Cells Enhances TGFB1 and IL10 Expressions in Epithelial Cells as Well as Neutrophils In Vitro: Prostaglandin E2 As a Main Regulator of Anti-Inflammatory Response in the Bovine Oviduct. AB - Sperm are allogenic to the female genital tract; however, oviducts provide optimal conditions for survival and capacitation of these non-self cells until fertilization. Recently, we showed that oviduct-conditioned media and prostaglandin E2 (PGE2) suppress sperm phagocytosis by polymorphonuclear neutrophils (PMNs) under physiological conditions. We hypothesized that sperm binding to bovine oviduct epithelial cells (BOECs) could change the local innate immunity via PGE2. As the first step to obtain basic information, sub-confluent BOEC monolayers were co-cultured with swim-up sperm for 2 h. BOECs with viable bound sperm were cultured for an additional 3, 6, 12, or 24 h. Then, we confirmed the impact of the sperm-BOEC binding on both BOECs and PMN gene expression. Immunohistochemistry revealed that BOECs strongly express TGFB1 and IL10 in the oviduct. Sperm binding to BOECs in culture induced the anti-inflammatory cytokines (TGFB1 and IL10) and PGE2 production by BOECs. Exogenous PGE2 in vitro suppressed pro-inflammatory cytokine expression (TNF and IL1B) in BOECs. Moreover, pre-exposure of PMNs to BOEC-conditioned media suppressed the TNF expression, but the BOEC media co-cultured with sperm stimulated PMNs to express TGFB1 and IL10, with increasing PGE2 secretion. Of note, exogenous PGE2 led PMNs in vitro to decrease their TNF expression and increase anti-inflammatory cytokines expression. Our findings strongly suggest that BOECs provide an anti inflammatory environment under physiological conditions and the sperm-BOEC binding further strengthens this milieu thus suppresses PMNs in the bovine oviduct. PGE2 is likely to drive this stable anti-inflammatory environment in the oviduct. PMID- 27662645 TI - Preface to special issue on "Hormones in normal and pathological pregnancies". PMID- 27662644 TI - Neuropharmacological and neurochemical evaluation of N-n-propyl-3 ethoxyquinoxaline-2-carboxamide (6n): a novel serotonergic 5-HT3 receptor antagonist for co-morbid antidepressant- and anxiolytic-like potential using traumatic brain injury model in rats. AB - BACKGROUND: Several preclinical studies have shown that serotonergic 5-HT3 receptor antagonists play an important role in the management of neuropsychiatric disorders, such as depression and anxiety. In the present study the compound "6n" (N-n-propyl-3-ethoxyquinoxaline-2-carboxamide), a novel 5-HT3 receptor antagonist with an optimal log P (2.52) and pA2 (7.6) value was screened for its neuro pharmacological potential in chronic rodent models of depression and anxiety named traumatic brain injury (TBI). METHODS: In this model, a 1 cm midline scalp incision was made, and the muscles were retracted to expose the skull. A stainless steel disc (10 mm in diameter and 3 mm in depth) was placed centrally between the lambda and bregma regions. The injury was induced using the impact acceleration model of TBI. Specifically, a 400 g metal weight was dropped from a height of 1 m guided by a straight pipe, onto the metal disc placed over the rat's skull. RESULTS: The behavioral anomalies of the TBI rats were attenuated by the chronic treatment of compound 6n (1 and 2 mg/kg, p.o.; 14 days) as observed by the modified open field test (ambulation, rearing, and fecal pellet), sucrose consumption test (% sucrose consumption), elevated plus maze [% open arm entries [OAE] and % time spent in open arm (TSOA)], and marble burying test (numbers). In addition, 6n also increased the levels of neurotransmitters (norepinephrine and serotonin) and brain derived neurotrophic factor (BDNF) in TBI rats. CONCLUSIONS: The result suggests that compound 6n exhibited antidepressant- and anxiolytic like effects in rodent models of depression and anxiety. PMID- 27662647 TI - Present and future aspects of dydrogesterone in prevention or treatment of pregnancy disorders: an outlook. AB - Over time, it became evident that with the use of micronized progesterone and dydrogesterone prevention or treatment of pregnancy disorders such as threatened miscarriage, recurrent (habitual) miscarriage, preterm labor or preeclampsia appears to be possible. The results so far obtained will be delineated and concepts of prevention or treatment are suggested with the aim to further explore these pregnancy disorders either by prevention or treatment concepts to obtain not only benefits to the mother and the fetus, but furthermore this results in benefits for lifetime for the individual, for the family and last but not least for society. PMID- 27662646 TI - Progesterone in normal and pathological pregnancy. AB - Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. It has been proposed and extensively used in the treatment of different gynecological pathologies as well as in assisted reproductive technologies and in the maintenance of pregnancy. Called "the pregnancy hormone", natural progesterone is essential before pregnancy and has a crucial role in its maintenance based on different mechanisms such as: modulation of maternal immune response and suppression of inflammatory response (the presence of progesterone and its interaction with progesterone receptors at the decidua level appears to play a major role in the maternal defense strategy), reduction of uterine contractility (adequate progesterone concentrations in myometrium are able to counteract prostaglandin stimulatory activity as well as oxytocin), improvement of utero-placental circulation and luteal phase support (it has been demonstrated that progesterone may promote the invasion of extravillous trophoblasts to the decidua by inhibiting apoptosis of extravillous trophoblasts). Once the therapeutic need of progesterone is established, the key factor is the decision of the best route to administer the hormone and the optimal dosage determination. Progesterone can be administered by many different routes, but the most utilized are oral, the vaginal and intramuscular administration. The main uses of progesterone are represented by: threatened miscarriage, recurrent miscarriage and preterm birth (in the prevention strategy, as a tocolytic agent and also in the maintenance of uterine quiescence). PMID- 27662648 TI - Pharmacogenomics in pain treatment. AB - The experience of chronic pain is one of the commonest reasons for seeking medical attention, being a major issue in clinical practice. While pain is a universal experience, only a small proportion of people who felt pain develop pain syndromes. In addition, painkillers are associated with wide inter individual variability in the analgesic response. This may be partly explained by the presence of single nucleotide polymorphisms in genes encoding molecular entities involved in pharmacodynamics and pharmacokinetics. However, uptake of this information has been slow due in large part to the lack of robust evidences demonstrating clinical utility. Furthermore, novel therapies, including targeting of epigenetic changes and gene therapy-based approaches are further broadening future options for the treatment of chronic pain. The aim of this article is to review the evidences behind pharmacogenetics (PGx) to individualize therapy (boosting the efficacy and minimizing potential toxicity) and genes implicated in pain medicine, in two parts: (i) genetic variability with pain sensitivity and analgesic response; and (ii) pharmacological concepts applied on PGx. PMID- 27662649 TI - The impact of CYP4F2, ABCB1, and GGCX polymorphisms on bleeding episodes associated with acenocoumarol in Russian patients with atrial fibrillation. AB - BACKGROUND: Oral anticoagulants are commonly used to treat patients with thromboembolic pathology. Genetic variations could influence personal response to anticoagulant drugs. Acenocoumarol (AC) is a vitamin K antagonist used in anticoagulant therapy and as a prophylaxis measure in Europe. In this study, we assessed the effect of CYP4F2 rs2108622, ABCB1, and GGCX polymorphisms on the safety profile and regime dosing of AC in patients with nonvalvular atrial fibrillation. METHODS: Fifty patients aged 40-70 years were included. All patients received AC in the dose of 1-6 mg daily with a target international normalized ratio of 2.0-3.0. Genotyping for polymorphism markers C3435T for the ABCB1 gene, rs2108622 for the CYP4F2 gene, and rs11676382 for the GGCX gene were designed using polymerase chain reaction and restriction fragment length polymorphism. Statistical analysis was performed using the Fisher exact test and the Mann-Whitney U test. RESULTS: We found that CYP4F2 rs2108622 CT carriers required a higher AC dose than CC (p=0.0366), and CT and TT carriers required a higher AC dose than CC (p=0.0314). CONCLUSIONS: We found that ABCB1 CT and TT genotypes are associated with a higher risk of bleeding. No influence of ABCB1 and GGCX polymorphisms on the doses of AC was established. CYP4F2 could still be a genetic factor responsible for the personal variability of AC metabolism. PMID- 27662650 TI - Study of Autophagy and Microangiopathy in Sural Nerves of Patients with Chronic Idiopathic Axonal Polyneuropathy. AB - Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy. PMID- 27662651 TI - Sequence Based Prediction of Antioxidant Proteins Using a Classifier Selection Strategy. AB - Antioxidant proteins perform significant functions in maintaining oxidation/antioxidation balance and have potential therapies for some diseases. Accurate identification of antioxidant proteins could contribute to revealing physiological processes of oxidation/antioxidation balance and developing novel antioxidation-based drugs. In this study, an ensemble method is presented to predict antioxidant proteins with hybrid features, incorporating SSI (Secondary Structure Information), PSSM (Position Specific Scoring Matrix), RSA (Relative Solvent Accessibility), and CTD (Composition, Transition, Distribution). The prediction results of the ensemble predictor are determined by an average of prediction results of multiple base classifiers. Based on a classifier selection strategy, we obtain an optimal ensemble classifier composed of RF (Random Forest), SMO (Sequential Minimal Optimization), NNA (Nearest Neighbor Algorithm), and J48 with an accuracy of 0.925. A Relief combined with IFS (Incremental Feature Selection) method is adopted to obtain optimal features from hybrid features. With the optimal features, the ensemble method achieves improved performance with a sensitivity of 0.95, a specificity of 0.93, an accuracy of 0.94, and an MCC (Matthew's Correlation Coefficient) of 0.880, far better than the existing method. To evaluate the prediction performance objectively, the proposed method is compared with existing methods on the same independent testing dataset. Encouragingly, our method performs better than previous studies. In addition, our method achieves more balanced performance with a sensitivity of 0.878 and a specificity of 0.860. These results suggest that the proposed ensemble method can be a potential candidate for antioxidant protein prediction. For public access, we develop a user-friendly web server for antioxidant protein identification that is freely accessible at http://antioxidant.weka.cc. PMID- 27662652 TI - Carbohydrate-Binding Non-Peptidic Pradimicins for the Treatment of Acute Sleeping Sickness in Murine Models. AB - Current treatments available for African sleeping sickness or human African trypanosomiasis (HAT) are limited, with poor efficacy and unacceptable safety profiles. Here, we report a new approach to address treatment of this disease based on the use of compounds that bind to parasite surface glycans leading to rapid killing of trypanosomes. Pradimicin and its derivatives are non-peptidic carbohydrate-binding agents that adhere to the carbohydrate moiety of the parasite surface glycoproteins inducing parasite lysis in vitro. Notably, pradimicin S has good pharmaceutical properties and enables cure of an acute form of the disease in mice. By inducing resistance in vitro we have established that the composition of the sugars attached to the variant surface glycoproteins are critical to the mode of action of pradimicins and play an important role in infectivity. The compounds identified represent a novel approach to develop drugs to treat HAT. PMID- 27662653 TI - High-Grade Salivary-Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to a Single Rituximab Course in Primary Sjogren's Syndrome: Data from the TEARS Randomized Trial. AB - PURPOSE: To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjogren's syndrome [pSS]. MATERIALS AND METHODS: Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion. The echostructure of each parotid and submandibular gland was graded on a scale of 0 to 4. Histologic minor salivary gland involvement was assessed by the focus score. Among rituximab-treated patients with available data (n = 14), half met the Sjogren's Syndrome Responder Index [SSRI]-30 definition of a response at week 24. RESULTS: The SGUS score correlated positively to the focus score [r = 0.61] and negatively to the UWSF [r = -0.68]. The focus score was not correlated to the UWSF. The median total SGUS grade at inclusion was 9 [6-11] in responders versus 16 [11-16] in non-responders [p = 0.04]. The proportion of SSRI-30 responders was 0% among patients with SGUS grade 4 and 88% among those with SGUS grade <=3. Low baseline SGUS scores were associated with sicca-related outcomes improvement, but not with fatigue or biological improvement. Median baseline focus score was 0.3 [0.0-1.3] in the responders versus 4.0 [2.7-5.3] in the non-responders [p = 0.02]. Baseline UWSF was not associated with the response rate. CONCLUSION: In patients with pSS, the highest SGUS grade or a high histological focus score is associated with absence of a response to a single rituximab course after 6 months. Further studies, including more patients and different treatment strategies, are required to confirm the clinical utility of these potential biomarkers in pSS. PMID- 27662654 TI - Varenicline and Risk of Self-Harm: A Nested Case-Control Study. AB - BACKGROUND: Smoking remains a serious public health concern. Pharmacotherapy for smoking cessation, including bupropion and varenicline, are proven means to increase quit rates. Post-marketing reports describing suicidal behaviours have raised concerns about the safety of varenicline. However, whether varenicline imparts a higher risk of suicide relative to bupropion remains uncertain. METHODS: A population-based nested case-control study in Ontario, Canada, from April 1, 2011 to March 31, 2015 was conducted. Subjects were residents of Ontario aged 18 years and older with publicly funded drug coverage receiving either bupropion or varenicline for smoking cessation. We defined cases were those with a hospitalization or emergency department visit for suicide or non-fatal self harm within 90 days of treatment. For each case, we identified up to fifty controls from the same cohort matched on age, sex, history of self-harm, use of selected psychotropic medications, alcohol abuse and prior admission to a mental health unit. Adjusted odds ratio were used to compare the risk of suicide/self harm of varenicline to bupropion. RESULTS: We identified 331 cases and 5,346 matched-controls. Following adjustment for potential confounders, we found that varenicline was not associated with an increased risk of suicide/self-harm relative to bupropion (adjusted odds ratio 1.15; 95% confidence interval 0.71 to 1.87). INTERPRETATION: Treatment with varenicline does not appear to significantly increase the risk of suicide or self-harm relative to bupropion. PMID- 27662656 TI - Association between Hair Cortisol Concentration and Adiposity Measures among Children and Parents from the "Healthy Start" Study. AB - BACKGROUND: Previous studies have suggested a direct association between hair cortisol concentration (HCC) and Body Mass Index (BMI), as well as other adiposity measures. However, these studies have mostly been conducted among adult populations. OBJECTIVE: To examine the association between HCC and different measures of adiposity among a selected group of children predisposed to obesity and their parents. METHODS: We conducted a cross-sectional study based on 363 children and their parents (301 mothers and 231 fathers) participating in the "Healthy Start" study. Linear regression analysis was used to investigate associations between HCC and adiposity measures while taking into account possible confounding factors. Analyses were performed examining the association between HCC and BMI, fat mass and fat free mass index Z-scores, as well as waist circumference and waist-hip ratio among the children. Likewise, the association between HCC and BMI among the parents was explored. Finally, we examined the association between parental HCC and children's adiposity measures. RESULTS: HCC was directly associated with a higher BMI among the fathers (0.49 kg/m2 [95% CI: 0.09, 0.90, P = 0.02] per 100 pg/mg) and the mothers (0.93 kg/m2 [95% CI: 0.24, 1.61, P = 0.01] per 100 pg/mg). We found no clear evidence of an association between HCC and adiposity measures among children. However, a high maternal HCC was associated with a high fat mass index and low fat free mass index z-score in the offspring (0.14 SD [95% CI: 0.02, 0.26, P = 0.02] and -0.17 SD [95% CI: 0.30, -0.05, P = 0.01] per 100 pg/mg, respectively). CONCLUSIONS: Our study found no evidence of an association between HCC and measures of adiposity among children predisposed to obesity. However, HCC may be directly associated with BMI among men and women, and maternal HCC may be related to a higher fat mass and a lower fat free mass among their children. PMID- 27662655 TI - NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude) Mice. AB - Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D) and negative (MDA-MB-231, SUM1315, and CN34BrM) human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes) was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model. PMID- 27662657 TI - MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas. AB - Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs.25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2.In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance. PMID- 27662658 TI - Synergistic activity of ALK and mTOR inhibitors for the treatment of NPM-ALK positive lymphoma. AB - ALK-positive Anaplastic Large Cell Lymphoma (ALCL) represents a subset of Non Hodgkin Lymphoma whose treatment benefited from crizotinib development, a dual ALK/MET inhibitor. Crizotinib blocks ALK-triggered pathways such as PI3K/AKT/mTOR, indispensable for survival of ALK-driven tumors.Despite the positive impact of targeted treatment in ALCL, resistant clones are often selected during therapy. Strategies to overcome resistance include the design of second generation drugs and the use of combined therapies that simultaneously target multiple nodes essential for cells survival. We investigated the effects of combined ALK/mTOR inhibition. We observed a specific synergistic effect of combining ALK inhibitors with an mTOR inhibitor (temsirolimus), in ALK+ lymphoma cells. The positive cooperation resulted in an increased inhibition of mTOR effectors, compared to single treatments, a block in G0/G1 phase and induction of apoptosis. The combination was able to prevent the selection of resistant clones, while long-term exposure to single agents led to the establishment of resistant cell lines, with either ALK inhibitor or temsirolimus. In vivo, mice injected with Karpas 299 cells and treated with low dose combination showed complete regression of tumors, while only partial inhibition was obtained in single agents treated mice. Upon treatment stop the combination was able to significantly delay tumor relapses. Re-challenge of relapsed tumors at a higher dose led to full regression of xenografts in the combination group, but not in mice treated with lorlatinib alone. In conclusion, our data suggest that the combination of ALK and mTOR inhibitors could be a valuable therapeutic option for ALK+ ALCL patients. PMID- 27662659 TI - Prognostic role of the lymph node ratio in node positive colorectal cancer: a meta-analysis. AB - The lymph node ratio (LNR) (i.e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71-2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14-3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems. PMID- 27662660 TI - Genomic characterization of liver metastases from colorectal cancer patients. AB - Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases (vs. non-tumoral colorectal tissues) while expressed at normal levels in their primary tumors, reflecting either an increased genomic instability of metastatic cells or theiradaption to the liver microenvironment. Newly deregulated metastatic transcripts included overexpression of APOA1, HRG, UGT2B4, RBP4 and ADH4 mRNAS and the miR-3180-3p, miR-3197, miR-3178, miR-4793 and miR-4440 miRNAs, together with decreased expression of the IGKV1-39, IGKC, IGKV1-27, FABP4 and MYLK mRNAS and the miR-363, miR-1, miR-143, miR-27b and miR-28-5p miRNAs. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and the cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlighted the activation of genes associated with the TGFbeta signaling pathway, -e.g. RHOA, SMAD2, SMAD4, SMAD5, SMAD6, BMPR1A, SMAD7 and MYC-, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis. PMID- 27662661 TI - Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells. AB - Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature of Grp94 is its translocation from the ER to the cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both the tumor pathology and anti-tumor therapy. We wanted to address the question of whether Grp94 could be measured as liquid marker in cancer patients in order to make predictions of diagnostic and therapeutic relevance for the tumor. To this aim, we performed an in-depth investigation on patients with primary tumors of the gastrointestinal (GI) tract, using different methodological approaches to detect Grp94 in tumor tissues, plasma and peripheral blood mononuclear cells (PBMCs). Results indicate that Grp94 is not only the antigen highly expressed in any tumor tissue and in cells of tumor infiltrates, mostly B lymphocytes, but it is also found in the circulation. However, the only form in which Grp94 was detected in the plasma of any patients and in B lymphocytes induced to proliferate, was that of stable complexes with Immunoglobulin (Ig)G. Using a specific immune-enzyme assay to measure plasma Grp94-IgG complexes, we showed that Grp94-IgG complexes were significantly increased in cancer patients compared to healthy control subjects, serving as diagnostic tumor biomarker. Results also demonstrate that the stimulation of patient PBMCs with Grp94-IgG complexes led to an increased secretion of inflammatory cytokines that might drive a potentially beneficial anti-tumor effect. PMID- 27662662 TI - Decreased TRPM7 inhibits activities and induces apoptosis of bladder cancer cells via ERK1/2 pathway. AB - Transient receptor potential melastatin 7 (TRPM7) functions as a Mg2+/Ca2+ permeable channel fused with a kinase domain and regulates various physical processes and diseases. However, its effects on pathogenesis of human bladder cancer (BCa) has not been clarified yet. Our microarray analysis has suggested that calcium signaling pathway is connected with bladder cancer via MAPK pathway. Therefore, we aim to investigate the mechanism of TRPM7 in BCa tumorigenesis by using BCa tissues compared with normal bladder epithelium tissues, as well as using distinct BCa cell lines (EJ, 5637 and T24). We observed increased TRPM7 expression and dysregulation of proteins involved in Epithelial-Mesenchymal Transition (EMT) in BCa tissues. Moreover, knockdown of TRPM7 in BCa cells reversed the EMT status, accompanied by increase of reactive oxygen species (ROS). Furthermore, TRPM7 deficiency could inhibit BCa cell proliferation, migration and invasion, as well as induce p-ERK1/2 and suppress PI3K/AKT at the protein level. Downregulation of TRPM7 promoted cell cycle arrest at G0/G1 phase and apoptosis in vitro, which could be recovered by pre-treatment with U0126 to deactivate ERK1/2, suggesting a close correlation between TRPM7 and the MAPK signaling pathway. Furthermore, a NOD/SCID mouse model transplanted using the BCa cells was established, revealing delayed tumor growth by reduced protein activity and mRNA transcription of TRPM7 in vivo. Our results suggested TRPM7 might be essential for BCa tumorigenesis by interfering BCa cell proliferation, motility and apoptosis. PMID- 27662663 TI - STC2 promotes the epithelial-mesenchymal transition of colorectal cancer cells through AKT-ERK signaling pathways. AB - The STC2 protein involves in carcinogenesis and progression of many cancers. It remains unclear how STC2 regulates the epithelial-mesenchymal transition (EMT) process and colorectal cancer (CRC) development. Here we systematically investigated STC2-activated early occurrence of EMT and CRC cell migration in vitro, clinical associations of STC2 with CRC development and patient survival. The secretion and expression level of STC2 were both greatly increased in EMT cells and CRC cells compared with the normal epithelial NCM460 cells. And the conditioned media from EMT cells stimulated epithelia and colon cancer cells to obtain EMT characteristics. STC2 overexpression promoted CRC cell growth and cell migration in vitro, and STC2 enhanced tumor growth in a mouse CRC-xenograft model. Corresponding to EMT marker expression changes, several critical signaling pathway molecules including pERK, pAKT, PI3K and Ras were remarkably increased either in NCM460 cells transfected with STC2 plasmids or in cells induced with exogenous STC2 protein. However blocking AKT-ERK signaling pathways attenuated STC2-activated EMT process. Furthermore the elevated STC2 expressions were also confirmed in 77 clinical tumor tissues and sera from CRC patients, and the increased STC2 in tumor tissues and sera correlated with tumor pathologic stage and poor survival for CRC patients. In conclusion, STC2 promotes CRC tumorigenesis and EMT progression through activating ERK/MEK and PI3K/AKT signaling pathways. STC2 protein is also a potential tumor biomarker for CRC diagnosis and prognosis. PMID- 27662665 TI - Metavir and FIB-4 scores are associated with patient prognosis after curative hepatectomy in hepatitis B virus-related hepatocellular carcinoma: a retrospective cohort study at two centers in China. AB - Although Metavir and Fibrosis-4 (FIB-4) scores are typically used to assess the severity of liver fibrosis, the relationship between these scores and patient outcome in hepatocellular carcinoma (HCC) is unclear. The aim of this study was to evaluate the prognostic value of the severity of hepatic fibrosis in HBV related HCC patients after curative resection. We examined the prognostic roles of the Metavir and preoperative FIB-4 scores in 432 HBV-HCC patients who underwent curative resection at two different medical centers located in western (Chongqing) and eastern (Shanghai) China. In the testing set (n = 108), the Metavir, FIB-4, and combined Metavir/FIB-4 scores were predictive of overall survival (OS) and recurrence-free survival (RFS). Additionally, they were associated with several clinicopathologic variables. In the validation set (n = 324), the Metavir, FIB-4, and combined Metavir/FIB-4 scores were associated with poor prognosis in HCC patients after curative resection. Importantly, in the negative alpha-fetoprotein subgroup (<= 20 ng/mL), the FIB-4 index (I vs. II) could discriminate between patient outcomes (high or low OS and RFS). Thus Metavir, preoperative FIB-4, and combined Metavir/FIB-4 scores are prognostic markers in HBV-HCC patients after curative hepatectomy. PMID- 27662668 TI - Continuous Blood Viscosity Monitoring System for Cardiopulmonary Bypass Applications. AB - This paper proposes an algorithm that estimates blood viscosity during cardiopulmonary bypass (CPB) and validates its application in clinical cases. The proposed algorithm involves adjustable parameters based on the oxygenator and fluid types and estimates blood viscosity based on pressure-flow characteristics of the fluid perfusing through the oxygenator. This novel nonlinear model requires four parameters that were derived by in vitro experiments. The results estimated by the proposed method were then compared with a conventional linear model to demonstrate the former's optimal curve fitting. The viscosity (etae) estimated using the proposed algorithm and the viscosity (eta) measured using a viscometer were compared for 20 patients who underwent mildly hypothermic CPB. The developed system was applied to ten patients, and etae was recorded for comparisons with hematocrit and blood temperature. The residual sum of squares between the two curve fittings confirmed the significant difference, with p < 0.001. etae and eta showed a very strong correlation with R2 = 0.9537 and p < 0.001. Regarding the mean coefficient of determination for all cases, the hematocrit and temperature showed weak correlations at 0.33 +/- 0.14 and 0.22 +/- 0.21, respectively. For CPB measurements of all cases, etae was more than 98% distributed in the range from 1 to 3 mPa?s. This new system for estimating viscosity may be useful for detecting various viscosity-related effects that may occur during CPB. PMID- 27662669 TI - Linear Subspace Ranking Hashing for Cross-Modal Retrieval. AB - Hashing has attracted a great deal of research in recent years due to its effectiveness for the retrieval and indexing of large-scale high-dimensional multimedia data. In this paper, we propose a novel ranking-based hashing framework that maps data from different modalities into a common Hamming space where the cross-modal similarity can be measured using Hamming distance. Unlike existing cross-modal hashing algorithms where the learned hash functions are binary space partitioning functions, such as the sign and threshold function, the proposed hashing scheme takes advantage of a new class of hash functions closely related to rank correlation measures which are known to be scale-invariant, numerically stable, and highly nonlinear. Specifically, we jointly learn two groups of linear subspaces, one for each modality, so that features' ranking orders in different linear subspaces maximally preserve the cross-modal similarities. We show that the ranking-based hash function has a natural probabilistic approximation which transforms the original highly discontinuous optimization problem into one that can be efficiently solved using simple gradient descent algorithms. The proposed hashing framework is also flexible in the sense that the optimization procedures are not tied up to any specific form of loss function, which is typical for existing cross-modal hashing methods, but rather we can flexibly accommodate different loss functions with minimal changes to the learning steps. We demonstrate through extensive experiments on four widely-used real-world multimodal datasets that the proposed cross-modal hashing method can achieve competitive performance against several state-of-the-arts with only moderate training and testing time. PMID- 27662664 TI - PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma. AB - Programmed Death-1 (PD-1), an inhibitory receptor expressed by activated lymphocytes, is involved in regulating T- and B-cell responses. PD-1 and its ligands are exploited by a variety of cancers to facilitate tumor escape through PD-1-mediated functional exhaustion of effector T cells. Here, we report that PD 1 is upregulated on Natural Killer (NK) cells from patients with Kaposi sarcoma (KS). PD-1 was expressed in a sub-population of activated, mature CD56dimCD16pos NK cells with otherwise normal expression of NK surface receptors. PD-1pos NK cells from KS patients were hyporesponsive ex vivo following direct triggering of NKp30, NKp46 or CD16 activating receptors, or short stimulation with NK cell targets. PD-1pos NK cells failed to degranulate and release IFNgamma, but exogenous IL-2 or IL-15 restored this defect. That PD-1 contributed to NK cell functional impairment and was not simply a marker of dysfunctional NK cells was confirmed in PD-1-transduced NKL cells. In vitro, PD-1 was induced at the surface of healthy control NK cells upon prolonged contact with cells expressing activating ligands, i.e. a condition mimicking persistent stimulation by tumor cells. Thus, PD-1 appears to plays a critical role in mediating NK cell exhaustion. The existence of this negative checkpoint fine-tuning NK activation highlights the possibility that manipulation of the PD-1 pathway may be a strategy for circumventing tumor escape not only from the T cell-, but also the NK-cell mediated immune surveillance. PMID- 27662670 TI - Gamifying Video Object Segmentation. AB - Video object segmentation can be considered as one of the most challenging computer vision problems. Indeed, so far, no existing solution is able to effectively deal with the peculiarities of real-world videos, especially in cases of articulated motion and object occlusions; limitations that appear more evident when we compare the performance of automated methods with the human one. However, manually segmenting objects in videos is largely impractical as it requires a lot of time and concentration. To address this problem, in this paper we propose an interactive video object segmentation method, which exploits, on one hand, the capability of humans to identify correctly objects in visual scenes, and on the other hand, the collective human brainpower to solve challenging and large-scale tasks. In particular, our method relies on a game with a purpose to collect human inputs on object locations, followed by an accurate segmentation phase achieved by optimizing an energy function encoding spatial and temporal constraints between object regions as well as human-provided location priors. Performance analysis carried out on complex video benchmarks, and exploiting data provided by over 60 users, demonstrated that our method shows a better trade-off between annotation times and segmentation accuracy than interactive video annotation and automated video object segmentation approaches. PMID- 27662666 TI - TIM-4 is expressed on invariant NKT cells but dispensable for their development and function. AB - T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes. Using TIM 4-deficient mice, we found that lack of TIM-4 did not disturb iNKT cell development, maturation, peripheral homeostasis and cytokine secretion. Moreover, TIM-4 deficiency did not alter the polarization of iNKT sublineages, including NKT1, NKT2 and NKT17. Finally, the mixed bone marrow transfer experiments further confirmed normal iNKT cell development and function from TIM-4-deficient bone marrow. In conclusion, our data suggest that TIM-4 is expressed on iNKT cells but dispensable for their development and function. PMID- 27662671 TI - Efficient & Effective Prioritized Matching for Large-Scale Image-Based Localization. AB - Accurately determining the position and orientation from which an image was taken, i.e., computing the camera pose, is a fundamental step in many Computer Vision applications. The pose can be recovered from 2D-3D matches between 2D image positions and points in a 3D model of the scene. Recent advances in Structure-from-Motion allow us to reconstruct large scenes and thus create the need for image-based localization methods that efficiently handle large-scale 3D models while still being effective, i.e., while localizing as many images as possible. This paper presents an approach for large scale image-based localization that is both efficient and effective. At the core of our approach is a novel prioritized matching step that enables us to first consider features more likely to yield 2D-to-3D matches and to terminate the correspondence search as soon as enough matches have been found. Matches initially lost due to quantization are efficiently recovered by integrating 3D-to-2D search. We show how visibility information from the reconstruction process can be used to improve the efficiency of our approach. We evaluate the performance of our method through extensive experiments and demonstrate that it offers the best combination of efficiency and effectiveness among current state-of-the-art approaches for localization. PMID- 27662672 TI - Data-Driven Methods for the Determination of Anterior-Posterior Motion in PET. AB - Physiological motion combined with elongated scanning times in PET leads to image degradation and quantification errors. Correction approaches usually require 1-D signals that can be obtained with hardware-based or data-driven methods. Most of the latter are optimized or limited to capture internal motion along the superior inferior (S-I) direction. In this work we present methods for also extracting anterior-posterior (A-P) motion from PET data and propose a set of novel weighting mechanisms that can be used to emphasize certain lines-of-response (LORs) for an increased sensitivity and better signal-to-noise ratio (SNR). The proper functioning of the methods was verified in a phantom experiment. Further, their application to clinical [18F]-FDG-PET data of 72 patients revealed that using the weighting mechanisms leads to signals with significantly higher spectral respiratory weights, i.e. signals with higher quality. Information about multi-dimensional motion is contained in PET data and can be derived with data driven methods. Motion models or correction techniques such as respiratory gating might benefit from the proposed methods as they allow to describe the three dimensional movements of PET-positive structures more precisely. PMID- 27662674 TI - A Unified Maximum Likelihood Framework for Simultaneous Motion and $T_{1}$ Estimation in Quantitative MR $T_{1}$ Mapping. AB - In quantitative MR T1 mapping, the spin-lattice relaxation time T1 of tissues is estimated from a series of T1 -weighted images. As the T1 estimation is a voxel wise estimation procedure, correct spatial alignment of the T1 -weighted images is crucial. Conventionally, the T1 -weighted images are first registered based on a general-purpose registration metric, after which the T1 map is estimated. However, as demonstrated in this paper, such a two-step approach leads to a bias in the final T1 map. In our work, instead of considering motion correction as a preprocessing step, we recover the motion-free T1 map using a unified estimation approach. In particular, we propose a unified framework where the motion parameters and the T1 map are simultaneously estimated with a Maximum Likelihood (ML) estimator. With our framework, the relaxation model, the motion model as well as the data statistics are jointly incorporated to provide substantially more accurate motion and T1 parameter estimates. Experiments with realistic Monte Carlo simulations show that the proposed unified ML framework outperforms the conventional two-step approach as well as state-of-the-art model-based approaches, in terms of both motion and T1 map accuracy and mean-square error. Furthermore, the proposed method was additionally validated in a controlled experiment with real T1 -weighted data and with two in vivo human brain T1 weighted data sets, showing its applicability in real-life scenarios. PMID- 27662673 TI - Segmentation Based Sparse Reconstruction of Optical Coherence Tomography Images. AB - We demonstrate the usefulness of utilizing a segmentation step for improving the performance of sparsity based image reconstruction algorithms. In specific, we will focus on retinal optical coherence tomography (OCT) reconstruction and propose a novel segmentation based reconstruction framework with sparse representation, termed segmentation based sparse reconstruction (SSR). The SSR method uses automatically segmented retinal layer information to construct layer specific structural dictionaries. In addition, the SSR method efficiently exploits patch similarities within each segmented layer to enhance the reconstruction performance. Our experimental results on clinical-grade retinal OCT images demonstrate the effectiveness and efficiency of the proposed SSR method for both denoising and interpolation of OCT images. PMID- 27662675 TI - Preclinical MRI-Guided Focused Ultrasound: A Review of Systems and Current Practices. AB - Effective preclinical research is a vital component in the development of MRI guided focused ultrasound (MRgFUS) and its translation to clinic. In this review, we seek to outline the challenges at hand for effective preclinical research, survey different solutions, and underline best practices. Furthermore, we summarize efforts to build and characterize dedicated preclinical MRgFUS equipment, including lab prototypes and available commercial products. Finally, we discuss constraints and considerations specific to using clinical MRgFUS equipment in preclinical research. Specifically, we examine additional hardware that has been used to adapt clinical MRgFUS equipment to better position, constrain, and image preclinical subjects, as well as software solutions that have been used to extend the potential and capabilities of clinical devices. PMID- 27662676 TI - Investigation and Modeling of an Acoustoelectric Sensor Setup for the Determination of the Longitudinal Viscosity. AB - We present a two transducer setup suited for the determination of the second coefficient of viscosity, sometimes also termed acoustic viscosity. We present the basic sensor setup and according models in frequency and time domain allowing to extract the acoustic viscosity from the measurement data. We illustrate the approach using experimental data obtained with a demonstrator device. The setup, which has potential for further miniaturization, is operated in the time domain. Unwanted spurious effects and imperfections, such as diffraction, acoustic matching losses, and transducer losses, are discussed and according calibration and correction strategies are presented. PMID- 27662677 TI - LMD Based Features for the Automatic Seizure Detection of EEG Signals Using SVM. AB - Achieving the goal of detecting seizure activity automatically using electroencephalogram (EEG) signals is of great importance and significance for the treatment of epileptic seizures. To realize this aim, a newly-developed time frequency analytical algorithm, namely local mean decomposition (LMD), is employed in the presented study. LMD is able to decompose an arbitrary signal into a series of product functions (PFs). Primarily, the raw EEG signal is decomposed into several PFs, and then the temporal statistical and non-linear features of the first five PFs are calculated. The features of each PF are fed into five classifiers, including back propagation neural network (BPNN), K nearest neighbor (KNN), linear discriminant analysis (LDA), un-optimized support vector machine (SVM) and SVM optimized by genetic algorithm (GA-SVM), for five classification cases, respectively. Confluent features of all PFs and raw EEG are further passed into the high-performance GA-SVM for the same classification tasks. Experimental results on the international public Bonn epilepsy EEG dataset show that the average classification accuracy of the presented approach are equal to or higher than 98.10% in all the five cases, and this indicates the effectiveness of the proposed approach for automated seizure detection. PMID- 27662678 TI - PCE-FR: A Novel Method for Identifying Overlapping Protein Complexes in Weighted Protein-Protein Interaction Networks Using Pseudo-Clique Extension Based on Fuzzy Relation. AB - Identifying overlapping protein complexes in protein-protein interaction (PPI) networks can provide insight into cellular functional organization and thus elucidate underlying cellular mechanisms. Recently, various algorithms for protein complexes detection have been developed for PPI networks. However, majority of algorithms primarily depend on network topological feature and/or gene expression profile, failing to consider the inherent biological meanings between protein pairs. In this paper, we propose a novel method to detect protein complexes using pseudo-clique extension based on fuzzy relation (PCE-FR). Our algorithm operates in three stages: it first forms the nonoverlapping protein substructure based on fuzzy relation and then expands each substructure by adding neighbor proteins to maximize the cohesive score. Finally, highly overlapped candidate protein complexes are merged to form the final protein complex set. Particularly, our algorithm employs the biological significance hidden in protein pairs to construct edge weight for protein interaction networks. The experiment results show that our method can not only outperform classical algorithms such as CFinder, ClusterONE, CMC, RRW, HC-PIN, and ProRank +, but also achieve ideal overall performance in most of the yeast PPI datasets in terms of composite score consisting of precision, accuracy, and separation. We further apply our method to a human PPI network from the HPRD dataset and demonstrate it is very effective in detecting protein complexes compared to other algorithms. PMID- 27662679 TI - Algorithms for the Majority Rule (+) Consensus Tree and the Frequency Difference Consensus Tree. AB - This article presents two new deterministic algorithms for constructing consensus trees. Given an input of phylogenetic trees with identical leaf label sets and leaves each, the first algorithm constructs the majority rule (+) consensus tree in time, which is optimal since the input size is , and the second one constructs the frequency difference consensus tree in time. PMID- 27662683 TI - Towards Batteryless Cardiac Implantable Electronic Devices-The Swiss Way. AB - Energy harvesting devices are widely discussed as an alternative power source for todays active implantable medical devices. Repeated battery replacement procedures can be avoided by extending the implants life span, which is the goal of energy harvesting concepts. This reduces the risk of complications for the patient and may even reduce device size. The continuous and powerful contractions of a human heart ideally qualify as a battery substitute. In particular, devices in close proximity to the heart such as pacemakers, defibrillators or bio signal (ECG) recorders would benefit from this alternative energy source. The clockwork of an automatic wristwatch was used to transform the hearts kinetic energy into electrical energy. In order to qualify as a continuous energy supply for the consuming device, the mechanism needs to demonstrate its harvesting capability under various conditions. Several in-vivo recorded heart motions were used as input of a mathematical model to optimize the clockworks original conversion efficiency with respect to myocardial contractions. The resulting design was implemented and tested during in-vitro and in-vivo experiments, which demonstrated the superior sensitivity of the new design for all tested heart motions. PMID- 27662684 TI - Design and Optimization of Ultrasonic Wireless Power Transmission Links for Millimeter-Sized Biomedical Implants. AB - Ultrasound has been recently proposed as an alternative modality for efficient wireless power transmission (WPT) to biomedical implants with millimeter (mm) dimensions. This paper presents the theory and design methodology of ultrasonic WPT links that involve mm-sized receivers (Rx). For given load (RL) and powering distance (d), the optimal geometries of transmitter (Tx) and Rx ultrasonic transducers, including their diameter and thickness, as well as the optimal operation frequency (fc) are found through a recursive design procedure to maximize the power transmission efficiency (PTE). First, a range of realistic fcs is found based on the Rx thickness constrain. For a chosen fc within the range, the diameter and thickness of the Rx transducer are then swept together to maximize PTE. Then, the diameter and thickness of the Tx transducer are optimized to maximize PTE. Finally, this procedure is repeated for different fcs to find the optimal fc and its corresponding transducer geometries that maximize PTE. A design example of ultrasonic link has been presented and optimized for WPT to a 1 mm3 implant, including a disk-shaped piezoelectric transducer on a silicon die. In simulations, a PTE of 2.11% at fc of 1.8 MHz was achieved for RL of 2.5 [Formula: see text] at [Formula: see text]. In order to validate our simulations, an ultrasonic link was optimized for a 1 mm3 piezoelectric transducer mounted on a printed circuit board (PCB), which led to simulated and measured PTEs of 0.65% and 0.66% at fc of 1.1 MHz for RL of 2.5 [Formula: see text] at [Formula: see text], respectively. PMID- 27662685 TI - Complete Neuron-Astrocyte Interaction Model: Digital Multiplierless Design and Networking Mechanism. AB - Glial cells, also known as neuroglia or glia, are non-neuronal cells providing support and protection for neurons in the central nervous system (CNS). They also act as supportive cells in the brain. Among a variety of glial cells, the star shaped glial cells, i.e., astrocytes, are the largest cell population in the brain. The important role of astrocyte such as neuronal synchronization, synaptic information regulation, feedback to neural activity and extracellular regulation make the astrocytes play a vital role in brain disease. This paper presents a modified complete neuron-astrocyte interaction model that is more suitable for efficient and large scale biological neural network realization on digital platforms. Simulation results show that the modified complete interaction model can reproduce biological-like behavior of the original neuron-astrocyte mechanism. The modified interaction model is investigated in terms of digital realization feasibility and cost targeting a low cost hardware implementation. Networking behavior of this interaction is investigated and compared between two cases: i) the neuron spiking mechanism without astrocyte effects, and ii) the effect of astrocyte in regulating the neurons behavior and synaptic transmission via controlling the LTP and LTD processes. Hardware implementation on FPGA shows that the modified model mimics the main mechanism of neuron-astrocyte communication with higher performance and considerably lower hardware overhead cost compared with the original interaction model. PMID- 27662686 TI - Towards a Reduced-Wire Interface for CMUT-Based Intravascular Ultrasound Imaging Systems. AB - Having intravascular ultrasound (IVUS) imaging capability on guide wires used in cardiovascular interventions may eliminate the need for separate IVUS catheters and expand the use of IVUS in a larger portion of the vasculature. High frequency capacitive micro machined ultrasonic transducer (CMUT) arrays should be integrated with interface electronics and placed on the guide wire for this purpose. Besides small size, this system-on-a-chip (SoC) front-end should connect to the back-end imaging system with a minimum number of wires to preserve the critical mechanical properties of the guide wire. We present a 40 MHz CMUT array interface SoC, which will eventually use only two wires for power delivery and transmits image data using a combination of analog-to-time conversion (ATC) and an impulse radio ultra-wideband (IR-UWB) wireless link. The proof-of-concept prototype ASIC consumes only 52.8 mW and occupies 4.07 [Formula: see text] in a 0.35- [Formula: see text] standard CMOS process. A rectifier and regulator power the rest of the SoC at 3.3 V from a 10 MHz power carrier that is supplied through a 2.4 m micro-coax cable with an overall efficiency of 49.1%. Echo signals from an 8-element CMUT array are amplified by a transimpedance amplifier (TIA) array and down-converted to baseband by quadrature sampling using a 40 MHz clock, derived from the power carrier. The ATC generates pulse-width-modulated (PWM) samples at 2 * 10 MS/s with 6 bit resolution, while the entire system achieved 5.1 ENOB. Preliminary images from the prototype system are presented, and alternative data transmission and possible future directions towards practical implementation are discussed. PMID- 27662687 TI - A Flexible, Micro-Lens-Coupled LED Stimulator for Optical Neuromodulation. AB - Optogenetics is a fast growing neuromodulation method, which can remotely manipulate the specific activities of genetically-targeted neural cells and associated biological behaviors with millisecond temporal precision through light illumination. Application of optogenetics in neuroscience studies has created an increased need for the development of light sources and the instruments for light delivery. This paper presents a micro-lens-coupled LED neural stimulator which includes a backside reflector and a frontside microlens for light collection and collimation. The device structure has been optimized using optical simulation and the optimized device is able to increase the volume of excitable tissues by 70.4%. Device prototypes have been fabricated and integrated based on an optimization of the device structure. The measurement results show that the light power increases by 99% at an effective penetration depth of 5 000 [Formula: see text] by the fabricated device under various voltages of 2.4-3.2 V. PMID- 27662689 TI - Breast Histopathological Image Retrieval Based on Latent Dirichlet Allocation. AB - In the field of pathology, whole slide image (WSI) has become the major carrier of visual and diagnostic information. Content-based image retrieval among WSIs can aid the diagnosis of an unknown pathological image by finding its similar regions in WSIs with diagnostic information. However, the huge size and complex content of WSI pose several challenges for retrieval. In this paper, we propose an unsupervised, accurate, and fast retrieval method for a breast histopathological image. Specifically, the method presents a local statistical feature of nuclei for morphology and distribution of nuclei, and employs the Gabor feature to describe the texture information. The latent Dirichlet allocation model is utilized for high-level semantic mining. Locality-sensitive hashing is used to speed up the search. Experiments on a WSI database with more than 8000 images from 15 types of breast histopathology demonstrate that our method achieves about 0.9 retrieval precision as well as promising efficiency. Based on the proposed framework, we are developing a search engine for an online digital slide browsing and retrieval platform, which can be applied in computer aided diagnosis, pathology education, and WSI archiving and management. PMID- 27662691 TI - Adaptive NN Control Using Integral Barrier Lyapunov Functionals for Uncertain Nonlinear Block-Triangular Constraint Systems. AB - A neural network (NN) adaptive control design problem is addressed for a class of uncertain multi-input-multi-output (MIMO) nonlinear systems in block-triangular form. The considered systems contain uncertainty dynamics and their states are enforced to subject to bounded constraints as well as the couplings among various inputs and outputs are inserted in each subsystem. To stabilize this class of systems, a novel adaptive control strategy is constructively framed by using the backstepping design technique and NNs. The novel integral barrier Lyapunov functionals (BLFs) are employed to overcome the violation of the full state constraints. The proposed strategy can not only guarantee the boundedness of the closed-loop system and the outputs are driven to follow the reference signals, but also can ensure all the states to remain in the predefined compact sets. Moreover, the transformed constraints on the errors are used in the previous BLF, and accordingly it is required to determine clearly the bounds of the virtual controllers. Thus, it can relax the conservative limitations in the traditional BLF-based controls for the full state constraints. This conservatism can be solved in this paper and it is for the first time to control this class of MIMO systems with the full state constraints. The performance of the proposed control strategy can be verified through a simulation example. PMID- 27662692 TI - Fuzzy Tracking Control for Nonlinear Networked Systems. AB - This paper studies the observer-based tracking control problem for discrete-time nonlinear networked control systems with parameter uncertainties and unmeasurable state variables. A network-induced constraint, i.e., the intermittent measurement loss, is considered in the controller design. The uncertain nonlinear system is described by an interval type-2 (IT2) fuzzy Takagi-Sugeno model, in which the lower and the upper membership functions with corresponding coefficients are used to capture and express uncertainties existing in the system. A premise-variables independent IT2 fuzzy observer is constructed to estimate the unmeasurable state variables, and then a novel IT2 fuzzy tracking controller is designed. Furthermore, sufficient criteria are established to guarantee the resulting closed-loop system to be stochastically stable. Finally, two examples are provided to show the effectiveness of the proposed approach. PMID- 27662693 TI - Gr-GDHP: A New Architecture for Globalized Dual Heuristic Dynamic Programming. AB - Goal representation globalized dual heuristic dynamic programming (Gr-GDHP) method is proposed in this paper. A goal neural network is integrated into the traditional GDHP method providing an internal reinforcement signal and its derivatives to help the control and learning process. From the proposed architecture, it is shown that the obtained internal reinforcement signal and its derivatives can be able to adjust themselves online over time rather than a fixed or predefined function in literature. Furthermore, the obtained derivatives can directly contribute to the objective function of the critic network, whose learning process is thus simplified. Numerical simulation studies are applied to show the performance of the proposed Gr-GDHP method and compare the results with other existing adaptive dynamic programming designs. We also investigate this method on a ball-and-beam balancing system. The statistical simulation results are presented for both the Gr-GDHP and the GDHP methods to demonstrate the improved learning and controlling performance. PMID- 27662694 TI - Objective Model Selection for Identifying the Human Feedforward Response in Manual Control. AB - Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false positive results. PMID- 27662695 TI - An Investigation on the Accuracy of Truncated DKLT Representation for Speaker Identification With Short Sequences of Speech Frames. AB - Speaker identification plays a crucial role in biometric person identification as systems based on human speech are increasingly used for the recognition of people. Mel frequency cepstral coefficients (MFCCs) have been widely adopted for decades in speech processing to capture the speech-specific characteristics with a reduced dimensionality. However, although their ability to decorrelate the vocal source and the vocal tract filter make them suitable for speech recognition, they greatly mitigate the speaker variability, a specific characteristic that distinguishes different speakers. This paper presents a theoretical framework and an experimental evaluation showing that reducing the dimension of features by applying the discrete Karhunen-Loeve transform (DKLT) to the log-spectrum of the speech signal guarantees better performance compared to conventional MFCC features. In particular with short sequences of speech frames, with typical duration of less than 2 s, the performance of truncated DKLT representation achieved for the identification of five speakers are always better than those achieved with the MFCCs for the experiments we performed. Additionally, the framework was tested on up to 100 TIMIT speakers with sequences of less than 3.5 s showing very good recognition capabilities. PMID- 27662696 TI - Adaptive Compressive Tracking via Online Vector Boosting Feature Selection. AB - Recently, the compressive tracking (CT) method has attracted much attention due to its high efficiency, but it cannot well deal with the large scale target appearance variations due to its data-independent random projection matrix that results in less discriminative features. To address this issue, in this paper, we propose an adaptive CT approach, which selects the most discriminative features to design an effective appearance model. Our method significantly improves CT in three aspects. First, the most discriminative features are selected via an online vector boosting method. Second, the object representation is updated in an effective online manner, which preserves the stable features while filtering out the noisy ones. Furthermore, a simple and effective trajectory rectification approach is adopted that can make the estimated location more accurate. Finally, a multiple scale adaptation mechanism is explored to estimate object size, which helps to relieve interference from background information. Extensive experiments on the CVPR2013 tracking benchmark and the VOT2014 challenges demonstrate the superior performance of our method. PMID- 27662697 TI - Adults Who Order Sugar-Sweetened Beverages: Sociodemographics and Meal Patterns at Fast Food Chains. AB - INTRODUCTION: Approximately 30% of adults consume sugar-sweetened beverages (SSBs) daily, many at fast food restaurants. Researchers examined fast food purchases to better understand which consumers order SSBs, particularly large SSBs. METHODS: Fast food customers in New York City and New Jersey provided receipts and participated in a survey during 2013-2014 (N=11,614). Logistic regression analyses predicted three outcomes: ordering no beverage or a non-SSB, a small/medium SSB, or a large SSB. Among respondents who ordered a beverage (n=3,775), additional analyses predicted number of beverage calories and odds of ordering an SSB. Covariates included demographic and behavioral factors. RESULTS: Respondents aged 18-29 years were 88% more likely to order a large SSB than a non SSB or no beverage, as compared with respondents aged >=50 years (p<0.001). Among respondents who purchased a beverage, respondents ordered more beverage calories with a large combination meal (+85.13 kcal, p=0.001) or if the restaurant had a large cup size >30 ounces (+36.07 kcal, p=0.001). Hispanic and Asian respondents were less likely to order a large SSB (AOR=0.49 and 0.52, respectively, both p<=0.026) than non-Hispanic white respondents. Odds of ordering a large SSB were higher for respondents who ate in the restaurant (AOR=1.66, p<0.001) or stated that they chose beverage based on price (AOR=2.02, p<0.001). CONCLUSIONS: Young adults and customers of restaurants with a larger cup size were more likely to purchase SSBs, and their beverage calories increased with meal size. Increased understanding of these factors is an important step toward limiting unhealthy SSB consumption. PMID- 27662699 TI - Erratum to 'Reconceptualising Risk in Childbirth' [Midwifery 38 (2016) 1-5]. PMID- 27662698 TI - Healthcare Provider Contact and Pre-exposure Prophylaxis in Baltimore Men Who Have Sex With Men. AB - INTRODUCTION: Pre-exposure prophylaxis (PrEP) safely and effectively prevents HIV in populations at high risk, including men who have sex with men (MSM). PrEP scale-up depends upon primary care providers and community-based organizations (CBOs) sharing PrEP information. This study aimed to determine whether healthcare provider or CBO contact was associated with PrEP awareness among Baltimore MSM. METHODS: This study used 2014 Baltimore MSM National HIV Behavioral Surveillance data, which included data on health care, HIV and sexually transmitted infection testing, and receipt of condoms from CBOs. In 2015, associations were estimated between healthcare contacts and PrEP awareness through logistic regression models controlling for age, race, and education and clustering by venue. Comparative analyses were conducted with HIV testing as outcome. RESULTS: There were 401 HIV negative participants, of whom 168 (42%) were aware of PrEP. Visiting a healthcare provider in the past 12 months, receiving an HIV test from a provider, and having a sexually transmitted infection test in the past 12 months were not significantly associated with PrEP awareness. PrEP awareness was associated with being out to a healthcare provider (OR=2.97, 95% CI=1.78, 4.96, p<0.001); being tested for HIV (OR=1.50, 95% CI=1.06, 2.13, p=0.023); and receiving condoms from an HIV/AIDS CBO (OR=2.59, 95% CI=1.43, 4.64, p=0.001). By contrast, HIV testing was significantly associated with most forms of healthcare contact. CONCLUSIONS: PrEP awareness is not associated with most forms of healthcare contact, highlighting the need for guidelines and trainings to support provider discussion of PrEP with MSM. PMID- 27662700 TI - Efficient polymeric material for separation of human hemoglobin. AB - In this study, negatively charged acrylic acid was used as a functional ligand to synthesise net-poly(2-hydroxyethyl methacrylate-co-acrylic acid) microparticles for the removal of hemoglobin having a positively charged Fe2+ ion in the core, as an alternative to conventional techniques to achieve a cost effective high capacity purification. The characterization of microparticles was performed via Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, the Brunauer - Emmett Teller surface area analysis, and swelling test methods. Optimum adsorption conditions such as pH, initial hemoglobin concentration, temperature, and interaction time were studied batch wise. The highest adsorption capacity of microparticles was observed at pH 7.4 as 1276.4 mg hemoglobin/g polymer. The reusability of microparticles was also promising with ~5% decrease in the adsorption capacity at the end of the five adsorption-desorption cycles. PMID- 27662702 TI - Prescribing powers for nurses. AB - Common sense demands that district nurses and health visitors be empowered to prescribe from a limited list of dressings and products. News that the vast majority of MPs support the initiative comes as no surprise. Nurse prescribing from a limited list has in fact won favour from the medical, pharmaceutical, consumer and nursing lobbies. Senior Government figures are also known to have certain sympathies with the measure. It's true to say that virtually all see the obvious merits of facilitating community nurses to carry out a more effective role. In 1989 the Government's Advisory Report outlined a workable framework for nurse prescribing. It included the provision of adequate training for the 28,000 nurses this legislation would effect. The groundwork has been done. Why then are we still waiting for some movement from the Department of Health? PMID- 27662701 TI - Immediate Dose-Response Effect of High-Energy Versus Low-Energy Extracorporeal Shock Wave Therapy on Cutaneous Microcirculation. AB - Elucidation of the precise mechanisms and therapeutic options of extracorporeal shock wave therapy (ESWT) is only at the beginning. Although immediate real-time effects of ESWT on cutaneous hemodynamics have recently been described, the dose response to different ESWT energies in cutaneous microcirculation has never been examined. Thirty-nine Sprague-Dawley rats were randomly assigned to three groups that received either focused high-energy shock waves (group A: total of 1000 impulses, 10 J) to the lower leg of the hind limb, focused low-energy shock waves (group B: total of 300 impulses, 1 J) or placebo shock wave treatment (group C: 0 impulses, 0 J) using a multimodality shock wave delivery system (Duolith SD-1 T Top, Storz Medical, Tagerwilen, Switzerland). Immediate microcirculatory effects were assessed with the O2C (oxygen to see) system (LEA Medizintechnik, Giessen, Germany) before and for 20 min after application of ESWT. Cutaneous tissue oxygen saturation increased significantly higher after high-energy ESWT than after low energy and placebo ESWT (A: 29.4% vs. B: 17.3% vs. C: 3.3%; p = 0.003). Capillary blood velocity was significantly higher after high-energy ESWT and lower after low-energy ESWT versus placebo ESWT (group A: 17.8% vs. group B: -22.1% vs. group C: -5.0%, p = 0.045). Post-capillary venous filling pressure was significantly enhanced in the high-energy ESWT group in contrast to the low-energy ESWT and placebo groups (group A: 25% vs. group B: 2% vs. group C: -4%, p = 0.001). Both high-energy and low-energy ESWT affect cutaneous hemodynamics in a standard rat model. High-energy ESWT significantly increases parameters of cutaneous microcirculation immediately after application, resulting in higher tissue oxygen saturation, venous filling pressure and blood velocity, which suggests higher tissue perfusion with enhanced oxygen saturation, in contrast to low-energy as well as placebo ESWT. Low-energy ESWT also increased tissue oxygen saturation, albeit to a lower extent, and decreases both blood velocity and venous filling pressure. Low-energy ESWT reduced tissue perfusion, but improved oxygen saturation immediately after the application. PMID- 27662703 TI - Waiting lists. AB - The number of waiting-list operations provided by the health service has fallen for the first time for nearly a decade, official figures show. PMID- 27662704 TI - MPs give strong backing to nurse prescribing. AB - MPs have given their overwhelming support to nurse prescribing, in a new RCN opinion poll. PMID- 27662705 TI - Rape at nursing home on derelict site. AB - New security measures have been introduced at a Watford nurses' home after a nurse was raped at knifepoint by a man who climbed into her room through an open window last week. PMID- 27662706 TI - Present education system is 'unlikely to survive'. AB - The current system of community nursing education is inappropriate and unlikely to survive, a nursing professor has warned. PMID- 27662708 TI - ? AB - Nursing Professor Jane Robinson chaired a West Midlands conference to raise awareness of the needs of gypsy and traveller communities last week. Health is just one area where they experience difficulties, delegates heard. She is pictured with Agnes Vranckx, Joint Secretary of the West European Council of Gypsies, left, and the Princess Royal, President of the Save the Children Fund. PMID- 27662707 TI - Ann Stewart. AB - Ann Stewart, English National Board Professional Adviser in Midwifery F.ducation and Supervision, who had been a practising midwife since 1954 and served as vice president of the Royal College of Midwives, died last week. PMID- 27662709 TI - Anti-smoking measures fall short. AB - Nurses and parents have welcomed Flealth Secretary William Waldegrave's announcement of new' measures to curb tobacco promotion but have warned that a total ban on advertising is still needed. PMID- 27662711 TI - PNs told to scrutinise GP contract. AB - Practice nurses have been told to look very critically at the work they do under the GP contract to ensure that the tasks help improve health. PMID- 27662710 TI - Appointment. AB - Nursing Standard has appointed Elizabeth Munro to its editorial advisory board. Ms Munro is currently employed as a community midwifery sister at Simpson Memorial Maternity Pavilion in Edinburgh. In addition to her involvement in all areas of childbirth and maternity services, she also has a keen interest in politics and current affairs. PMID- 27662713 TI - A&E nurses 'need trauma care help'. AB - Accident and emergency nurses must have access to trauma care training to stem Britain's high preventable death toll, a tutor on a pioneering new course urged last week. PMID- 27662712 TI - Non-psychotic patients 'not helped by CPNs'. AB - Community psychiatric nurses are ineffective in solving the problems of non- psychotic patients, the first report from a three-year Department of Health funded study shows. PMID- 27662714 TI - Nupe conference. AB - A charterfor nursing advocacy to strengthen the nurse's role in exercising accountability and professional responsibility has been called for in a motion to be debated at NUPE's national conference at Scarborough in May. PMID- 27662715 TI - Nurses 'connive' to cover doctors' mistakes. AB - Nurses and midwives are conniving in covering up for doctors' mistakes, a leading patient rights advocate claimed at a London ethics conference. PMID- 27662716 TI - Detail of contracts still fairly crude'. AB - The detail and financial arrangements of many new NHS contracts are still fairly crude and nurses need not fear their activities will be restricted by them, the Association of British Paediatric Nurses annual conference was told. PMID- 27662717 TI - ? AB - Looking good: North Manchester Health Authority held open days at clinics and health centres last week to promote its new video refraction machine which enables early detection of sight problems in children. The event was part of Squint Awareness Week which aimed to increase eye testing in children. PMID- 27662718 TI - Parliament. AB - Cases of food poisoningin England and Wales have almost tripled over the last eight years. PMID- 27662719 TI - 'NHS gives poor thought to staff caring at home'. AB - The NHS is bottom of the league when it comes to offering staff understanding over their caring role in the home, a new study has shown. PMID- 27662722 TI - ? AB - Working together: But not all doctor-nurse working relationships are as beneficial to patients as this, says Professor Julia Brooking. PMID- 27662723 TI - Research drawn away from the universities. AB - University nursing departments are losing out to polytechnics and colleges of higher education in the battle to recruit researchers, Tony Butterworth, Professor of Community Nursing at the University of Manchester, reported at the recent conference. PMID- 27662721 TI - Is it time to heal the differences? AB - Relationships between doctors and nurses have deteriorated to the point where patient care is suffering, a nursing professor has claimed. PMID- 27662725 TI - RGN training fails at independent learning. AB - The registered general nurse training programme fails to encourage students to become independent learners, an assessment by Sue Torkington, Lecturer at the East Sussex and West Kent Institute of Nursing, reveals. PMID- 27662724 TI - Quality testing the qa instruments. AB - A study aiming to validate the quality assurance instruments Qual Pacs, Monitor and Senior Monitor is being carried out at the Nursing Research Unit at King's College, London. PMID- 27662726 TI - Northern Ireland nurses lack knowledge of AIDS. AB - Nurses in Northern Ireland have serious gaps in their knowledge of AIDS and negative attitudes towards people defined as 'at risk' according to a recent study. PMID- 27662727 TI - Carers of the elderly need emotional support. AB - Respite care facilities are effective in reducing the stress suffered by informal carers, but nurses still do not recognise the difficulties faced by people caring for the elderly at home, a study has shown. PMID- 27662728 TI - Reasons for caesarean delivery are unclear. AB - A Glasgow study has shown that 18 per cent of a sample of fifty primigravidaewomen who had emergency Caesarean sections were still unsure or mistaken on the reasons for their operations three months after the event. PMID- 27662729 TI - Infertility treatment and neonatal units. AB - Expansion of infertility services should not go ahead without regard for the impact on services for newborn babies. PMID- 27662731 TI - Lactational amenorrhoea as contraceptive method. AB - The lactational amenorrhoea method might offer excellent contraceptive protection beyond six months, irrespective of when supplements are introduced. PMID- 27662730 TI - Magnesium and chronic fatigue syndrome. AB - Magnesium might have a beneficial effect on chronic fatigue syndrome (CFS). PMID- 27662733 TI - Cost-effectiveness of hospital immunisation. AB - Opportunistic hospital immunisation of children may not be cost-effective. PMID- 27662732 TI - Ultrasound effective in early pregnancy. AB - Transvaginal ultrasonography in gynaecological emergencies may produce hospital savings, researchers say. PMID- 27662734 TI - Coming full circle. AB - 'We have succeeded in protecting the health of the nation and the generation on which the future of the nation depends.' PMID- 27662735 TI - Corporate concerns. AB - Sponsorship is the latest spin-off from a market approach to health care that is worrying nurses. Despite protests from the United Kingdom Central Council and others that sponsorship can compromise a nurse's position and force a breach of the Code of Professional Conduct, the health service is not prepared to pass up the chance of extra cash. PMID- 27662736 TI - Golden opportunities. AB - Central Manchester Health Authority has turned nurse specialism into something of an art form. They boast among their staff a specialist in rheumatology, one in epilepsy and another in urology. The source of these developments, according to respiratory care nurse Christine Bell, was the highly successful Manchester Diabetes Centre which opened in 1988. The outpatient services manager at Manchester Royal Infirmary was so impressed by this work that there was a great incentive to expand the idea. When Christine was first interviewed, just over two years ago, she and her colleagues were, to some extent, able to decide for themselves which areas they wanted to work in. Respiratory medicine had always been a particular interest of Christine's, especially the management of asthma, where she knew there was a need. PMID- 27662737 TI - Calling for bigger CATS. AB - I thought it would be helpful to put the record straight in response to G Cornfield's letter on credit ratings for students on 'traditional' and Project 2000 programmes (Project 2000 Paper Tigers, Nursing Standard, April 3). PMID- 27662738 TI - Child abuse: your role. AB - The handling of the child abuse investigations by social workers is being called into question following recent events in Rochdale and the Orkneys. PMID- 27662739 TI - Someone's about to learn. AB - I have recently written to a number of nursing colleges asking for details of their registered general nurse training courses. PMID- 27662740 TI - Emergencies welcomed. AB - As many readers will know, the annual Royal College of Nursing Congress will soon be upon us, and by now copies of the agenda should be finding their way to various membership groups. PMID- 27662742 TI - ? PMID- 27662741 TI - A curfew on women. AB - Shortly after I read Christopher Goodall's excellent piece on pornography (A Social Disease? Nursing Standard, March 20), the British Safety Council launched a code to protect lone women drivers whose cars break down. PMID- 27662743 TI - Information exchange. AB - I am an enrolled nurse working in haematology clinics. PMID- 27662744 TI - Care Staff in Transition Care Staff in Transition P Allen , J Pahl , L Quine Her Majesty's Stationery Office 164pp L9.65 0-11-321209-7 [Formula: see text]. AB - Community care for people with mental handicaps has long been Government policy. Care Staff in Transition is a research book which examines the impact on those nursing staff making the transition from the once relative security of large, long-stay NHS hospitals to local authority community homes - the current trend in mental handicap services' philosophy. PMID- 27662745 TI - Counselling the coronary patient and partner Counselling the coronary patient and partner D R Thompson Scutari Press 122pp L11.95 1-871364-42-6 [Formula: see text]. AB - In one of the latest titles to be added to the RCN 'Research series', David Thompson provides an in-depth, highly readable study of a hospital-based counselling project. He looks at the monitoring and comparison of 'anxiety, depression, satisfaction and knowledge in male coronary patients and their spouses'. PMID- 27662747 TI - Common legal questionsLegal experts look at some of the most common questions of law raised by Nursing Standard readers. This week - understaffing, clinical grading, and 'good Samaritan' acts. AB - There exists among nurses the widespread and general, fear that they are unwittingly exposing themselves to litigation and professional misconduct in their daily practice. stems mainly from the facts that they perceive a general increase in legal claims against professionals, and that many of them are extending their roles. Queries like the following occur as a result. PMID- 27662749 TI - Time to tell all. AB - Midwives are always bemoaning how badly maligned and misunderstood they are - a situation well exemplified by last week's London ethics conference. PMID- 27662748 TI - Telephone test call? AB - Who do you contact when you get yourself into a twist? PMID- 27662750 TI - Ghost-busting gossiper John Naish reveals more haunting hearsay. AB - The starched-white ghost of Victorian values stalks nurses' homes once again - in the guise of the new National Health Service tenancy agreement. PMID- 27662751 TI - Research for a star? AB - Research must now be accepted as the cornerstone of nursing practice. In response to the call of the Briggs Committee ( 1 ) that 'nursing should be a research based profession', nurses have sought to justify both their own existence and to raise the status of the profession by scientific study. PMID- 27662752 TI - Six months' labour. AB - Four Nursing Standard readers have now contacted me to say that they have successfully obtained job shares since I began writing this column in September 1990. Only two of them were women with young children. 'Grace', a 57-year-old nurse requested a job share so that she could help her retired older sister care for their elderly mother, who required nursing care following an illness. PMID- 27662753 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Clare Ward, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX (Fax 081-423 3867). PMID- 27662754 TI - Self-locked aptamer probe mediated cascade amplification strategy for highly sensitive and selective detection of protein and small molecule. AB - In this work, a novel self-locked aptamer probe mediated cascade amplification strategy has been constructed for highly sensitive and specific detection of protein. First, the self-locked aptamer probe was designed with three functions: one was specific molecular recognition attributed to the aptamer sequence, the second was signal transduction owing to the transduction sequence, and the third was self-locking through the hybridization of the transduction sequence and part of the aptamer sequence. Then, the aptamer sequence specific recognized the target and folded into a three-way helix junction, leading to the release of the transduction sequence. Next, the 3'-end of this three-way junction acted as primer to trigger the strand displacement amplification (SDA), yielding a large amount of primers. Finally, the primers initiated the dual-exponential rolling circle amplification (DE-RCA) and generated numerous G-quadruples sequences. By inserting the fluorescent dye N-methyl mesoporphyrin IX (NMM), enhanced fluorescence signal was achieved. In this strategy, the self-locked aptamer probe was more stable to reduce the interference signals generated by the uncontrollable folding in unbounded state. Through the cascade amplification of SDA and DE-RCA, the sensitivity was further improved with a detection limit of 3.8 * 10(-16) mol/L for protein detection. Furthermore, by changing the aptamer sequence of the probe, sensitive and selective detection of adenosine has been also achieved, suggesting that the proposed strategy has good versatility and can be widely used in sensitive and selective detection of biomolecules. PMID- 27662755 TI - Hydrogen deuterium exchange mass spectrometry in biopharmaceutical discovery and development - A review. AB - Protein therapeutics have emerged as a major class of biopharmaceuticals over the past several decades, a trend that has motivated the advancement of bioanalytical technologies for protein therapeutic characterization. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful and sensitive technique that can probe the higher order structure of proteins and has been used in the assessment and development of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and biosimilar antibodies. It has also been used to quantify protein-ligand, protein-receptor and other protein-protein interactions involved in signaling pathways. In manufacturing and development, HDX-MS can validate storage formulations and manufacturing processes for various biotherapeutics. Currently, HDX-MS is being refined to provide additional coverage, sensitivity and structural specificity and implemented on the millisecond timescale to reveal residual structure and dynamics in disordered domains and intrinsically disordered proteins. PMID- 27662756 TI - Detecting Alzheimer's disease biomarkers: From antibodies to new bio-mimetic receptors and their application to established and emerging bioanalytical platforms - A critical review. AB - The failure of therapeutic treatment of Alzheimer's disease (AD) patients can be related to the late onset of symptoms and, consequently, to a delayed pharmacological aid to counteract neurodegenerative progression. This is coupled to the fact that the diagnosis based on clinical criteria alone introduces high misdiagnosis rate. The availability of assessed biomarkers is therefore of crucial importance not only to counteract late diagnosis, but also to manage patients at high risk of AD development eligible for novel therapies. At the present time, amyloid-beta peptides (Abeta1-40 and Abeta1-42 isoforms), alone or in combination with Tau protein (total and phosphorylated forms (p-tau)) constitute reliable AD biomarkers and result highly predictive of progression to AD dementia in patients with mild cognitive impairment (MCI), the earliest clinical presentation of AD. Improvement of existing diagnostic tools must take advantage of innovative bioanalytical approaches. In this review, starting from commercially available diagnostic platforms based on antibodies as recognition elements, we intended to provide a double point of view on the issue: 1) progresses achieved on innovative bioanalytical platforms (mainly sensors and biosensors) by using antibodies as consolidated receptors; 2) advance on promising bio-mimetic receptors alternative to antibodies in AD research, and their applications on conventional or innovative analytical platforms. In particular, we first focused on optical- (Propagating and Localized Surface Plasmon Resonance, named here SPR and LSPR) and electrochemical (voltammetric and impedimetric) transduction principles. Together with bioanalytical assays for AD biomarkers quantification, works aimed to investigate and understand their behavior, characteristics, and roles will also be considered in the discussion. An increasing interest in new emerging biomimetic receptors for AD diagnosis, as a promising alternative to antibodies is noticed, thus the description of peptides, peptoids, nanobodies, aptamers, and molecularly imprinted polymers and their role as recognition elements in different bioanalytical platforms is also reviewed. Features and limits are discussed, together with potentialities and perspectives of their further applicability to clinical routine AD analysis. PMID- 27662757 TI - Analysis of (210)Pb in water samples with plastic scintillation resins. AB - (210)Pb is a radioactive lead isotope present in the environment as member of the (238)U decay chain. Since it is a relatively long-lived radionuclide (T1/2 = 22.2 years), its analysis is of interest in radiation protection and the geochronology of sediments and artwork. Here, we present a method for analysing (210)Pb using plastic scintillation resins (PSresins) packaged in solid-phase extraction columns (SPE cartridge). The advantages of this method are its selectivity, the low limit of detection, as well as reductions in the amount of time and reagents required for analysis and the quantity of waste generated. The PSresins used in this study were composed of a selective extractant (4',4"(5")-Di-tert butyldicyclohexano-18-crown-6 in 1-octanol) covering the surface of plastic scintillation microspheres. Once the amount of extractant (1:1/4) and medium of separation (2 M HNO3) were optimised, PSresins in SPE cartridges were calibrated with a standard solution of (210)Pb. (210)Pb could be fully separated from its daughters, (210)Bi and (210)Po, with a recovery value of 91(3)% and detection efficiency of 44(3)%. Three spiked water samples (one underground and two river water samples) were analysed in triplicates with deviations lower than 10%, demonstrating the validity of the PS resin method for (210)Pb analysis. PMID- 27662758 TI - Bayesian peak tracking: A novel probabilistic approach to match GCxGC chromatograms. AB - A novel peak tracking method based on Bayesian statistics is proposed. The method consists of assigning (i.e. tracking) peaks from two GCxGC-FID data sets of the same sample taken in different conditions. Opposed to traditional (i.e. deterministic) peak tracking algorithms, in which the assignment problem is solved with a unique solution, the proposed algorithm is probabilistic. In other words, we quantify the uncertainty of matching two peaks without excluding other possible candidates, ranking the possible peak assignments regarding their posterior probability. This represents a significant advantage over existing deterministic methods. Two algorithms are presented: the blind peak tracking algorithm (BPTA) and peak table matching algorithm (PTMA). PTMA method was able to assign correctly 78% of a selection of peaks in a GCxGC-FID chromatogram of a diesel sample and proved to be extremely fast. PMID- 27662759 TI - Estimating complicated baselines in analytical signals using the iterative training of Bayesian regularized artificial neural networks. AB - The present work deals with the development of a new baseline correction method based on the comparative learning capabilities of artificial neural networks. The developed method uses the Bayes probability theorem for prevention of the occurrence of the over-fitting and finding a generalized baseline. The developed method has been applied on simulated and real metabolomic gas-chromatography (GC) and Raman data sets. The results revealed that the proposed method can be used to handle different types of baselines with cave, convex, curvelinear, triangular and sinusoidal patterns. For further evaluation of the performances of this method, it has been compared with benchmarking baseline correction methods such as corner-cutting (CC), morphological weighted penalized least squares (MPLS), adaptive iteratively-reweighted penalized least squares (airPLS) and iterative polynomial fitting (iPF). In order to compare the methods, the projected difference resolution (PDR) criterion has been calculated for the data before and after the baseline correction procedure. The calculated values of PDR after the baseline correction using iBRANN, airPLS, MPLS, iPF and CC algorithms for the GC metabolomic data were 4.18, 3.64, 3.88, 1.88 and 3.08, respectively. The obtained results in this work demonstrated that the developed iterative Bayesian regularized neural network (iBRANN) method in this work thoroughly detects the baselines and is superior over the CC, MPLS, airPLS and iPF techniques. A graphical user interface has been developed for the suggested algorithm and can be used for easy implementation of the iBRANN algorithm for the correction of different chromatography, NMR and Raman data sets. PMID- 27662760 TI - Electrospun Pd nanoparticles loaded on Vulcan carbon/ conductive polymeric ionic liquid nanofibers for selective and sensitive determination of tramadol. AB - In the present work a sensitive and selective electrochemical sensor was fabricated based on a glassy carbon electrode which has been modified with Pd nanoparticles loaded on Vulcan carbon/conductive polymeric ionic liquid composite nanofibers. The nanostructures were characterized by UV-Vis, FT-IR, FESEM, EDX and XRD techniques. The electrochemical study of the modified electrode, as well as its efficiency for the electrooxidation of tramadol was described in 0.1 M phosphate buffered solution (PBS) (pH 7.0) using cyclic voltammetry, linear sweep voltammetry, chronoamperometry and square wave voltammetry as diagnostic techniques. It has been found that application of the composite nanofibers result in a sensitivity enhancement and a considerable decrease in the anodic overpotential, leading to negative shifts about 200 mV in peak potential. The results exhibit a linear dynamic range from 0.05 MUM to 200 MUM and a detection limit of 0.015 MUM for tramadol. Finally, the modified electrode was used for the determination of tramadol in pharmaceutical and biological samples. PMID- 27662761 TI - Turbulence in microfluidics: Cleanroom-free, fast, solventless, and bondless fabrication and application in high throughput liquid-liquid extraction. AB - This paper addresses an important breakthrough in the deployment of ultra-high adhesion strength microfluidic technologies to provide turbulence at harsh flow rate conditions. This paper is only, to our knowledge, the second reporting on the generation of high flow rate-assisted turbulence in microchannels. This flow solves a crucial bottleneck in microfluidics: the generation of high throughput homogeneous mixings. We focused on the fabrication of bulky polydimethylsiloxane (PDMS) microchips (without any interfaces) rather than the laborious surface modifications that were employed in the first reporting about turbulence-assisted microfluidics. The fabrication is cleanroom-free, simple, low-cost, fast, solventless, and bondless requiring only a laboratory oven. More specifically, our method relies on the shaping of a nylon scaffold, cure of PDMS with embedded nylon, and removal of this scaffold. The scaffold was obtained by manually wrapping nylon threads. The withdrawing out of the scaffold was completed in few seconds using only a plier. Such microchannels endured flow rates of up to 60.0 mL min(-1) with a strikingly low elastic deformation. The importance in producing turbulence into microscale channels was successfully shown in liquid-liquid extractions. The great energy dissipation rate relative to the turbulence created high throughput and efficient extractions in microfluidics for the first time. The residence time was only 0.01 s at 25.0 mL min(-1) (total flow rate of the immiscible phases). In addition, the partition coefficient determined in a single run was similar to that obtained by the conventional batch shake-flask method that was realized in triplicate. PMID- 27662762 TI - Identification of triacylglycerol using automated annotation of high resolution multistage mass spectral trees. AB - High complexity of identification for non-target triacylglycerols (TAGs) is a major challenge in lipidomics analysis. To identify non-target TAGs, a powerful tool named accurate MS(n) spectrometry generating so-called ion trees is used. In this paper, we presented a technique for efficient structural elucidation of TAGs on MS(n) spectral trees produced by LTQ Orbitrap MS(n), which was implemented as an open source software package, or TIT. The TIT software was used to support automatic annotation of non-target TAGs on MS(n) ion trees from a self-built fragment ion database. This database includes 19108 simulate TAG molecules from a random combination of fatty acids and corresponding 500582 self-built multistage fragment ions (MS <= 3). Our software can identify TAGs using a "stage-by-stage elimination" strategy. By utilizing the MS(1) accurate mass and referenced RKMD, the TIT software can discriminate unique elemental composition candidates. The regiospecific isomers of fatty acyl chains will be distinguished using MS(2) and MS(3) fragment spectra. We applied the algorithm to the selection of 45 TAG standards and demonstrated that the molecular ions could be 100% correctly assigned. Therefore, the TIT software could be applied to TAG identification in complex biological samples such as mouse plasma extracts. PMID- 27662763 TI - Identification and characterization of isomeric N-glycans of human alfa-acid glycoprotein by stable isotope labelling and ZIC-HILIC-MS in combination with exoglycosidase digestion. AB - In this study, a ZIC-HILIC-MS methodology for the analysis of N-glycan isomers was optimized to obtain greater detection sensitivity and thus identify more glycan structures in hAGP. In a second step, this method was combined with glycan reductive isotope labelling (GRIL) through [(12)C6]/[(13)C6]-aniline and exoglycosidase digestion to characterize the different glycan isomers. The GRIL method allows the peak areas resulting from two different labelled samples to be compared, since neither retention time shifts nor variations in the ionization of glycans between these samples are obtained. First, sialic acid linkage assignations were performed for most hAGP glycan isomers with alpha2-3 sialidase digestion. Bi-, tri- and tetraantennary glycan isomers with different terminal sialic acid linkages to galactose (alpha2-3 or alpha2-6) were assigned, and the potential of this technique for the structural characterization of isobaric isomers was therefore demonstrated. Furthermore, fucose linkage isomers of hAGP glycans were also characterized using this isotope-labelling approach in combination with alpha1-3,4 fucosidase and beta1-4 galactosidase digestion. alpha1-3 antennary fucoses and alpha1-6 core fucosylation were detected in hAGP fucosylated glycans. These established methodologies can be extremely useful for patho-glycomic studies to characterize glycoproteins of biomedical interest and find novel glycan isomers that could be used as biomarkers in cancer research. PMID- 27662764 TI - Paper spray mass spectrometry and PLS-DA improved by variable selection for the forensic discrimination of beers. AB - Paper spray mass spectrometry (PS-MS) combined with partial least squares discriminant analysis (PLS-DA) was applied for the first time in a forensic context to a fast and effective differentiation of beers. Eight different brands of American standard lager beers produced by four different breweries (141 samples from 55 batches) were studied with the aim at performing a differentiation according to their market prices. The three leader brands in the Brazilian beer market, which have been subject to fraud, were modeled as the higher-price class, while the five brands most used for counterfeiting were modeled as the lower-price class. Parameters affecting the paper spray ionization were examined and optimized. The best MS signal stability and intensity was obtained while using the positive ion mode, with PS(+) mass spectra characterized by intense pairs of signals corresponding to sodium and potassium adducts of malto-oligosaccharides. Discrimination was not apparent neither by using visual inspection nor principal component analysis (PCA). However, supervised classification models provided high rates of sensitivity and specificity. A PLS DA model using full scan mass spectra were improved by variable selection with ordered predictors selection (OPS), providing 100% of reliability rate and reducing the number of variables from 1701 to 60. This model was interpreted by detecting fifteen variables as the most significant VIP (variable importance in projection) scores, which were therefore considered diagnostic ions for this type of beer counterfeit. PMID- 27662765 TI - Inner filter effect and the onset of concentration dependent red shift of synchronous fluorescence spectra. AB - The phenomenon of concentration dependent red shift, often observed in synchronous fluorescence spectra (SFS) of monofluorophoric as well as multifluorophoric systems at high chromophore concentrations, is known to have good analytical advantages. This was previously understood in terms of large inner filter effect (IFE) through the introduction of a derived absorption spectral profile that closely corresponds to the SFS profile. Using representative monofluorophoric and multifluorophoric systems, it is now explained how the SF spectral maximum changes with concentration of the fluorophore. For dilute solutions of monofluorophores the maximum is unchanged as expected. It is shown here that the onset of red shift of SFS maximum of both the mono as well as the multifluorophoric systems must occur at the derived absorption spectral parameter value of 0.32 that corresponds to the absorbance value of 0.87. This value is unique irrespective of the nature of the fluorophore under study. For monofluorophoric systems, the wavelength of derived absorption spectral maximum and the wavelength of synchronous fluorescence spectral maximum closely correspond with each other in the entire concentration range. In contrast, for multifluorophoric systems like diesel and aqueous humic acid, large deviations were noted that could be explained as to be due to the presence of non fluorescing chromophores in the system. This work bridges the entire fluorophore concentration range over which the red shift of SFS maximum sets in; and in the process it establishes the importance of the derived absorption spectral parameter in understanding the phenomenon of concentration dependent red shift of SFS maximum. PMID- 27662766 TI - Direct and ultrasensitive optofluidic-based immunosensing assay of aflatoxin M1 in dairy products using organic solvent extraction. AB - Aflatoxin M1 (AFM1), a highly toxic secondary metabolite, is present in a wide range of dairy products. In this study, we designed a simple, low-cost, reusable, and easy-to-operate immunosensing method for ultrasensitive detection of AFM1 in dairy products by using a portable evanescent wave-based optofluidic biosensing platform (EOBP). The developed method provides the minimum detection limit of 5 ng/L, which is below the most restrictive standard imposed by the current regulations for AFM1 in dairy products. The effect of several organic solvents, such as methanol, acetone, and acetonitrile, on the binding reaction of antibody antigen in heterogeneous and homogeneous solutions was evaluated. Although the effect of organic solvents on the homogeneous binding reaction between antibody and antigen is more significant than that of heterogeneous binding reaction between antibody in solution and antigen immobilized onto the sensor surface, the fluorescence signal detected by EOBP is linearly dependent on AFM1 concentration. Therefore, AFM1 can be directly quantified even if the samples contain a certain organic solvent concentration. The robustness and stability of AFM1-ovalbumin conjugate allow the regeneration of modified biosensor surface for more than 200 times, thereby achieving a cost-effective and reliable AFM1 determination. The proposed method provides a rapid, ultrasensitive, and reliable AFM1 determination in dairy products without complicated sample pretreatment process. PMID- 27662767 TI - Small molecule probes finely differentiate between various ds- and ss-DNA and RNA by fluorescence, CD and NMR response. AB - Two small molecules showed intriguing properties of analytical multipurpose probes, whereby one chromophore gives different signal for many different DNA/RNA by application of several highly sensitive spectroscopic methods. Dyes revealed pronounced fluorescence ratiomeric differentiation between ds-AU-RNA, AT-DNA and GC-DNA in approximate order 10:8:1. Particularly interesting, dyes showed specific fluorimetric response for poly rA even at 10-fold excess of any other ss RNA, and moreover such emission selectivity is preserved in multicomponent ss-RNA mixtures. The dyes also showed specific chiral recognition of poly rU in respect to the other ss-RNA by induced CD (ICD) pattern in visible range (400-500 nm), which was attributed to the dye-side-chain contribution to binding (confirmed by absence of any ICD band for reference compound lacking side-chain). Most intriguingly, minor difference in the side-chain attached to dye chromophore resulted in opposite sign of dye-ICD pattern, whereby differences in NMR NOESY contacts and proton chemical shifts between two dye/oligo rU complexes combined with MD simulations and CD calculations attributed observed bisignate ICD to the dimeric dye aggregate within oligo rU. PMID- 27662768 TI - Magnetic porous carbon nanocomposites derived from metal-organic frameworks as a sensing platform for DNA fluorescent detection. AB - Metal-organic frameworks (MOFs) have emerged as very fascinating functional materials due to their tunable nature and diverse applications. In this work, we prepared a magnetic porous carbon (MPC) nanocomposite by employing iron containing MOFs (MIL-88A) as precursors through a one-pot thermolysis method. It was found that the MPC can absorb selectively single-stranded DNA (ssDNA) probe to form MPC/ssDNA complex and subsequently quench the labelled fluorescent dye of the ssDNA probe, which is resulted from the synergetic effect of magnetic nanoparticles and carbon matrix. Upon the addition of complementary target DNA, however, the absorbed ssDNA probe could be released from MPC surface by forming double-stranded DNA with target DNA, and accompanied by the recovery of the fluorescence of ssDNA probe. Based on these findings, a sensing platform with low background signal for DNA fluorescent detection was developed. The proposed sensing platform exhibits high sensitivity with detection limit of 1 nM and excellent selectivity to specific target DNA, even single-base mismatched nucleotide can be distinguished. We envision that the presented study would provide a new perspective on the potential applications of MOF-derived nanocomposites in biomedical fields. PMID- 27662769 TI - Slug-flow microextraction coupled with paper spray mass spectrometry for rapid analysis of complex samples. AB - Analysis of trace compounds in small-volume complex samples is of importance for forensic, clinical, pharmaceutical, environmental, and life science investigation. In this study, we reported the coupling of slug-flow microextraction with paper spray mass spectrometry for rapid analysis of trace analytes in small volume of complicated biological samples such as whole blood, milk, and body fluid, etc. The method is performed by applying a disposable glass capillary for rapid extraction of a small amount of complex samples using a small amount of organic solvent; the loaded organic solvent was then spotted onto a paper triangle and dried out; subsequently, a high voltage and some spray solvent were applied onto the paper triangle for mass spectrometric analysis. By using the proposed method, high sensitivity and satisfactory precision for quantitative analysis of trace macrolide antibiotics in whole bloods and milks as well as perfluorinated compounds in individual small organisms have been successfully achieved. In addition, investigation of bioaccumulation of perfluorinated compounds in individual small organisms has been reached. PMID- 27662770 TI - Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant. AB - The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9 fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of abundant l-AAs. PMID- 27662771 TI - Dose-Optimized Computed Tomography for Screening and Follow-Up of Solid Pulmonary Nodules in Obesity: A Phantom Study. AB - To determine the lowest CT radiation dose-level at maintained image-quality and high sensitivity for detection of pulmonary-nodules in obesity. Single-energy CT with tin-filtration was performed in a chest-phantom with solid pulmonary-nodules simulating over-weight and obesity. CTDIvol of the standard-protocol was 0.41 mGy, subsequent scans were obtained at 1/2 and 1/4 dose-levels. Images were reconstructed using FBP and advanced-modeled iterative reconstruction (ADMIRE). Noise, image-quality, and sensitivity for nodule-detection were assessed. Noise was significantly reduced with ADMIRE (standard-dose: 73%; 1/2 dose: 73%; 1/4 dose: 71.2%; p < 0.001) compared to FBP. Image-quality was diagnostic for all images reconstructed with ADMIRE5. Sensitivity for nodule-detection was 100% at 1/2 and 1/4 dose-level for the phantom simulating over-weight and 97.37% (1/2 dose-level) and 81.58% (1/4 dose-level) for the phantom simulating obesity using ADMIRE5. In conclusion, single-energy CT with tin-filtration and ADMIRE shows potential for dose reduction in a phantom experiment down to 0.1 mGy in over weight and 0.21 mGy obese subjects, while image quality and sensitivity for detection of solid pulmonary nodules remains high. PMID- 27662772 TI - Manganese-induced cadmium stress tolerance in rice seedlings: Coordinated action of antioxidant defense, glyoxalase system and nutrient homeostasis. AB - The accumulation of cadmium (Cd) alters different physiological and biochemical attributes that affect plant growth and yield. In our study, we investigated the regulatory role of supplemental manganese (Mn) on hydroponically grown rice (Oryza sativa L. cv. BRRI dhan29) seedlings under Cd-stress conditions. Exposure of 14-d-old seedlings to 0.3mM CdCl2 for three days caused growth inhibition, chlorosis, nutrient imbalance, and higher Cd accumulation. Higher Cd uptake caused oxidative stress through lipid peroxidation, loss of plasma membrane integrity, and overproduction of reactive oxygen species (ROS) and methylglyoxal (MG). The exogenous application of 0.3mM MnSO4 to Cd-treated seedlings partly recovered Cd-induced water loss, chlorosis, growth inhibition, and nutrient imbalance by reducing Cd uptake and its further translocation to the upper part of the plant. Supplemental Mn also reduced Cd-induced oxidative damage and lipid peroxidation by improved antioxidant defense and glyoxalase systems through enhancing ROS and MG detoxification, respectively. PMID- 27662773 TI - [King Vision video laryngoscope for severe post burn contracture neck: an encouraging experience]. AB - BACKGROUND AND OBJECTIVES: Managing the airway of post burn contracture of the neck has always been challenging to anesthesiologists as it limits the alignment of oro-pharyngo-laryngeal axes because of functional and anatomical deformities that occur as a result of long standing contractures. Here the role of the King Vision video laryngoscope which is the latest in the series of video laryngoscope has been evaluated for such patients. CASE REPORT: A 35 year old male patient with post burn contracture of neck was scheduled for release of the contracture. As the patient had had fixed flexion deformity of the neck we did not attempt the conventional laryngoscopy. Instead we opted for King Vision video laryngoscope. CONCLUSION: We therefore conclude that King Vision videolaryngoscope can be used for difficult airway situations like post burn contracture of neck. PMID- 27662774 TI - Quality and developmental rate of embryos produced with sex-sorted and conventional semen from superovulated dairy cattle. AB - This study investigated the effect of sex-sorted semen compared with conventional semen on the outcome of embryo recovery, placing special emphasis on the quality, and developmental stage of embryos. Data were analyzed for 443 embryo collections with sex-sorted semen (SEX group) and 1528 with conventional semen (CONV group) in superovulated dairy heifers and cows. The insemination protocol for conventional semen included two inseminations, comprising a total dose of 30 million sperm passing into the uterine body. For sex-sorted semen, two (30%) to three (70%) deep uterine inseminations were performed, the total dose ranging from eight to 12 million sperm. The data were analyzed separately for heifers and cows. The total number of recovered structures was similar among the groups. The number of viable embryos decreased in the SEX groups compared with the CONV (with 1.4 and 3.2 fewer embryos in heifers and cows, correspondingly, P < 0.001), and correspondingly the proportions of unfertilized ova and degenerated embryos increased in the SEX groups (P < 0.001). The proportion of unsuccessful collections, yielding no transferable embryos, increased in the SEX groups for both heifers (from 7.2% to 11.2%, P = 0.025) and cows (from 9.0% to 20.7%, P < 0.001). Regarding the quality of viable embryos, the quality grades were superior in the CONV group compared with the SEX group for heifers (P < 0.001) and cows (P < 0.001). The proportion of grade 1 embryos decreased by 6.5 percentage points in heifers and 11.9 percentage points in cows when sex-sorted semen was used. Correspondingly, the proportions of grade 2 and 3 embryos increased in heifers and cows when sexed semen was used. The mean developmental stages of embryo collections were numerically slightly lower in the SEX group. In heifers, the delay in developmental stage was statistically significant (P = 0.001), but in cows, there was only a tendency toward that (P = 0.067). In conclusion, sex sorted sperm decreased the transferable embryo yield and increased the risk of a recovery yielding no transferable embryos. Furthermore, use of sex-sorted semen decreased the proportion of grade 1 embryos. In addition, it also seemed to delay embryonic development, although the delay in embryonic development was minimal and its biological relevance remains undefined. Despite the compromised embryo production, taken into account the optimization of recipient resources, the use of sex-sorted semen is advantageous, especially in superovulated heifers, which are of most importance in the modern breeding strategies using genomic selection. PMID- 27662775 TI - Human factors analysis of the CardioQuick Patch(r): A novel engineering solution to the problem of electrode misplacement during 12-lead electrocardiogram acquisition. AB - INTRODUCTION: The CardioQuick Patch(r) (CQP) has been developed to assist operators in accurately positioning precordial electrodes during 12-lead electrocardiogram (ECG) acquisition. This study describes the CQP design and assesses the device in comparison to conventional electrode application. METHODS: Twenty ECG technicians were recruited and a total of 60 ECG acquisitions were performed on the same patient model over four phases: (1) all participants applied single electrodes to the patient; (2) all participants were then re trained on electrode placement and on how to use the CQP; (3) participants were randomly divided into two groups, the standard group applied single electrodes and the CQP group used the CQP; (4) after a one day interval, the same participants returned to carry out the same procedure on the same patient (measuring intra-practitioner variability). Accuracy was measured with reference to pre-marked correct locations using ultra violet ink. NASA-TLK was used to measure cognitive workload and the Systematic Usability Scale (SUS) was used to quantify the usability of the CQP. RESULTS: There was a large difference between the minimum time taken to complete each approach (CQP=38.58s vs. 65.96s). The standard group exhibited significant levels of electrode placement error (V1=25.35mm+/-29.33, V2=18.1mm+/-24.49, V3=38.65mm+/-15.57, V4=37.73mm+/-12.14, V5=35.75mm+/-15.61, V6=44.15mm+/-14.32). The CQP group had statistically greater accuracy when placing five of the six electrodes (V1=6.68mm+/-8.53 [p<0.001], V2=8.8mm+/-9.64 [p=0.122], V3=6.83mm+/-8.99 [p<0.001], V4=14.90mm+/-11.76 [p<0.001], V5=8.63mm+/-10.70 [p<0.001], V6=18.13mm+/-14.37 [p<0.001]). There was less intra-practitioner variability when using the CQP on the same patient model. NASA TLX revealed that the CQP did increase the cognitive workload (CQP group=16.51%+/-8.11 vs. 12.22%+/-8.07 [p=0.251]). The CQP also achieved a high SUS score of 91+/-7.28. CONCLUSION: The CQP significantly improved the reproducibility and accuracy of placing precordial electrodes V1, V3-V6 with little additional cognitive effort, and with a high degree of usability. PMID- 27662776 TI - Validation of the vessel-specific leads (VSLs) for detection of acute ischemia on a dataset with non-ischemic ST-segment deviation. AB - BACKGROUND: Existing criteria recommended by ACC/ESC for identifying patients with ST elevation myocardial infarction (STEMI) from the 12-lead ECG perform with high specificity (SP) but low sensitivity (SE). In our previous studies, we found that the SE of acute ischemia detection can be markedly improved without any loss of SP by calculating, from the 12-lead ECG, ST deviation in 3 "optimal" vessel specific leads (VSLs). To further validate the method, we evaluated the SP performance using a dataset with non-ischemic ST-segment changes. METHODS: 12 lead ECGs of 100 patients (75 males/25 females, age range 12-83years, average age 52years) were retrieved from a centralized ECG management system at Skane University Hospital, Lund, Sweden. These ECGs were chosen to represent five subgroups with various causes of pathological ST deviation, other than acute coronary occlusion: a) ventricular preexcitation (n=12), b) acute pericarditis (n=26), c) early repolarization syndrome (ERS) (n=14), d) left ventricular hypertrophy (LVH) with "strain" (n=26), and e) left bundle branch block (LBBB) (n=22). ECGs with inadequate signal quality, heart rate exceeding 120bpm and/or atrial flutter were not selected for this study population. Both STEMI criteria and VSLs criteria with and without a new augmented LVH-specific derived lead were tested. SP, calculated for each subgroup and combined, was used as the performance measure for comparison. RESULTS: SP test results for the STEMI criteria vs. the VSLs method without the augmented LVH lead were 100% vs. 92%, 4% vs. 88%, 29% vs. 100%, 100% vs. 77%, and 64% vs. 68% for the five subgroups with preexcitation, pericarditis, ERS, LVH, and LBBB, respectively. For the whole group, SP was 57% for the STEMI criteria and 83% for the VSLs criteria; this improvement was statistically significant (p<0.001). With the augmented LVH lead, SP for the VSLs improved from 77% to 96% for the LVH subgroup and SP for the other subgroups remained unchanged. For the whole study group, SP improved from 83% to 88%. CONCLUSION: Based on these results, we conclude that the VSLs criteria are not only more sensitive in detecting acute ischemia but also more specific in recognizing patients with non-ischemic ST deviation than the existing STEMI criteria. This finding needs to be further corroborated on a larger patient population with AMI prevalence typical of the population presenting to the emergency room. PMID- 27662777 TI - Computer-assisted image processing 12 lead ECG model to diagnose hyperkalemia. AB - BACKGROUND: We sought to develop an improved 12 lead ECG model to diagnose hyperkalemia by use of traditional and novel parameters. METHODS: We retrospectively analyzed ECGs in consecutive hyperkalemic patients (serum potassium (K)>5.3mEq/L) by blinded investigators with normokalemic ECGs as internal controls. Potassium levels were modeled using general linear mixed models followed by refit with standardized variables. Optimum sensitivity and specificity were determined using cut point analysis of ROC-AUC. RESULTS: The training set included 236 ECGs (84 patients) and validation set 97 ECGs (23 patients). Predicted K=(5.2354)+(0.03434*descending T slope)+(-0.2329*T width)+( 0.9652*reciprocal of new QRS width>100msec). ROC-AUC in the validation set was 0.78 (95% CI 0.69-0.88). Maximum specificity of the model was 84% for K>5.91 with sensitivity of 63%. CONCLUSION: ECG model incorporating T-wave width, descending T-wave slope and new QRS prolongation improved hyperkalemia diagnosis over traditional ECG analysis. PMID- 27662778 TI - [Integration of internet and social networks within health strategies]. PMID- 27662779 TI - Ocular disposition of treosulfan and its active epoxy-transformers following intravenous administration in rabbits. AB - Treosulfan (TREO) has an established position in chemotherapy of advanced ovarian cancer but has been also applied in uveal melanoma patients. Moreover, it is used as an orphan drug for a myeloablative conditioning prior to stem cell transplantation. In this paper, biodistribution of prodrug TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into aqueous humor of the eye was studied for the first time. For that purpose, alone TREO and the mixture of TREO, S,S-EBDM and S,S-DEB were administered intravenously to New Zealand White rabbits. The three analytes were determined in plasma and aqueous humor by validated HPLC methods and pharmacokinetic calculations were performed in WinNonlin. After the infusion of TREO, the aqueous humor/plasma Cmax ratio and area under the curve ratio amounted 0.04 and 0.10 for TREO, and 1.1 and 2.2 for S,S-EBDM, respectively. Following the bolus injection of the mixture of the prodrug and its epoxides, the aqueous humor/plasma Cmax ratios for TREO, S,S-EBDM and S,S-DEB were 0.05, 0.66, and 4.0, respectively. The presented results indicate a poor penetration of TREO into the eye, which may impair systemic treatment of ocular tumors but is beneficial in terms of a lack of clinically relevant ophthalmic adverse effects. PMID- 27662780 TI - Metformin prevents glucotoxicity by alleviating oxidative and ER stress-induced CD36 expression in pancreatic beta cells. AB - AIM/HYPOTHESIS: Cluster determinant 36 (CD36), a fatty acid transporter, was reported to have a pivotal role in glucotoxicity-induced beta cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression, and it is unknown whether this action can be counteracted by metformin. In the present study, we showed that metformin counteracts glucotoxicity by alleviating oxidative and endoplasmic reticulum (ER) stress-induced CD36 expression. METHODS: We used primary rat islets as well as INS-1 cells for 72h to 24h with 30mM glucose, respectively. Thapsigargin was used as strong ER stressor, and Sulfo-N succinimidyl oleate (SSO) and RNA interference were chosen for CD36 inhibition. Free fatty acid uptake was measured by radioisotope tracing technique. RESULTS: Exposure of isolated rat islets to high glucose (HG) for 3days decreased insulin and pancreatic duodenal homeobox1 (Pdx1) mRNA expression, with the suppression of glucose-stimulated insulin secretion (GSIS) along with elevation of reactive oxygen species (ROS) levels. Incubation with metformin restored insulin and Pdx1 mRNA expression with significant improvements in GSIS and decrease in ROS production. HG exposure in INS-1 cells increased free fatty acid uptake via induction of CD36 along with impaired insulin and Pdx1 mRNA expression. Moreover, thapsigargin also increased the induction of CD36 expression. Metformin blocked HG- and thapsigargin-induced CD36 expression. In addition, the simultaneous inhibition of intracellular ROS production by metformin or CD36 activation by SSO or CD36 siRNA significantly decreased the apoptotic response in HG-treated INS-1 cells. CONCLUSION/INTERPRETATION: In conclusion, metformin conferred protection against HG-induced apoptosis of pancreatic beta cells, largely by interfering with ROS production, and inhibited the CD36-mediated free fatty acid influx. This report provides evidence that the inhibition of CD36 may have potential therapeutic effects against hyperglycemia-induced beta cell damage in diabetes. PMID- 27662782 TI - Review and analysis of over 40 years of space plant growth systems. AB - The cultivation of higher plants occupies an essential role within bio regenerative life support systems. It contributes to all major functional aspects by closing the different loops in a habitat like food production, CO2 reduction, O2 production, waste recycling and water management. Fresh crops are also expected to have a positive impact on crew psychological health. Plant material was first launched into orbit on unmanned vehicles as early as the 1960s. Since then, more than a dozen different plant cultivation experiments have been flown on crewed vehicles beginning with the launch of Oasis 1, in 1971. Continuous subsystem improvements and increasing knowledge of plant response to the spaceflight environment has led to the design of Veggie and the Advanced Plant Habitat, the latest in the series of plant growth systems. The paper reviews the different designs and technological solutions implemented in higher plant flight experiments. Using these analyses a comprehensive comparison is compiled to illustrate the development trends of controlled environment agriculture technologies in bio-regenerative life support systems, enabling future human long duration missions into the solar system. PMID- 27662781 TI - Elevated serum total bilirubin levels are negatively associated with major diabetic complications among Chinese senile diabetic patients. AB - AIMS: This study aimed to evaluate the association between total bilirubin (TBiL) and major diabetic complications among Chinese senile diabetic patients. METHODS: A cross-sectional study was conducted in all the cadre sanitariums in Beijing, between May 2012 and December 2014. All the diagnoses of diabetic complications were extracted from the medical records including chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease, and ischemic stroke. RESULTS: The mean age of the 1839 senile diabetic patients were 87.4+/ 4.0 (80-102years) and mean TBiL level was 13.2+/-6.0MUmol/L. The prevalence of chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease and ischemic stroke was 13.8%, 17.8%, 5.8%, 62.5%, and 44.5%, respectively. TBiL level was negatively correlated with age, weight, SBP, TC, FBG, 2hPG, diabetic duration and positively correlated with HDL-C. Prevalence of all five diseases gradually decreased with the increase of TBiL level (p<0.05). Also, number of diabetic complications showed a decreasing trend along with TBiL tertiaries. After adjusted age, education, marital status, current smoking, current drinking, physical activity >=0.5h/day, BMI, hypertension, dyslipidemia, treatment and control status of diabetes, patients with higher TBiL level were at significantly decreased ORs for prevalence of major diabetic complications. The ORs were 0.97 (95%CI: 0.96-0.99), 0.90 (95%CI: 0.87-0.93), 0.98 (95%CI: 0.97 0.99), 0.97 (95%CI: 0.95-.99) and 0.98 (95%CI: 0.97-0.99) for chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease and ischemic stroke (p<0.005). Similar results were obtained when TBiL was used as tertiary variable. CONCLUSION: Higher TBiL was significantly associated with lower prevalence of major diabetic complication among senile diabetic patients, and this association was graded with TBiL level and independent of age and control status of diabetes. PMID- 27662783 TI - Performance in hippocampus- and PFC-dependent cognitive domains are not concomitantly impaired in rats exposed to 20cGy of 1GeV/n (56)Fe particles. AB - NASA is currently conducting ground based experiments to determine whether the radiation environment that astronauts will encounter on deep space missions will have an impact on their long-term health and their ability to complete the various tasks during the mission. Emerging data suggest that exposure of rodents to mission-relevant HZE radiation doses does result in the impairment of various neurocognitive processes. An essential part of mission planning is a probabilistic risk assessment process that takes into account the likely incidence and severity of a problem. To date few studies have reported the impact of space radiation in a format that is amenable to PRA, and those that have only reported data for a single cognitive process. This study has established the ability of individual male Wistar rats to conduct a hippocampus-dependent (spatial memory) task and a cortex-dependent (attentional set shifting task) 90 days after exposure to 20cGy 1GeV/n (56)Fe particles. Radiation-induced impairment of performance in one cognitive domain was not consistently associated with impaired performance in the other domain. Thus sole reliance upon a single measure of cognitive performance may substantially under-estimate the risk of cognitive impairment, and ultimately it may be necessary to establish the likelihood that mission-relevant HZE doses will impair performance in the three or four cognitive domains that NASA considers to be most critical for mission success, and build a PRA using the composite data from such studies. PMID- 27662784 TI - Mechanisms of phosphene generation in ocular proton therapy as related to space radiation exposure. AB - Particle therapy provides an opportunity to study the human response to space radiation in ground-based facilities. On this basis, a study of light flashes analogous to astronauts' phosphenes reported by patients undergoing ocular proton therapy has been undertaken. The influence of treatment parameters on phosphene generation was investigated for 430 patients treated for a choroidal melanoma at the proton therapy centre of the Institut Curie (ICPO) in Orsay, France, between 2008 and 2011. 60% of them report light flashes, which are predominantly (74%) blue. An analysis of variables describing the patient's physiology, properties of the tumour and dose distribution shows that two groups of tumour and beam variables are correlated with phosphene occurrence. Physiology is found to have no influence on flash triggering. Detailed correlation study eventually suggests a possible twofold mechanism of phosphene generation based on (i) indirect Cerenkov light in the bulk of the eye due to nuclear interactions and radioactive decay and (ii) direct excitation of the nerve fibres in the back of the eye and/or radical excess near the retina. PMID- 27662785 TI - Charged particle spectra measured during the transit to Mars with the Mars Science Laboratory Radiation Assessment Detector (MSL/RAD). AB - The Mars Science Laboratory (MSL) started its 253-day cruise to Mars on November 26, 2011. During cruise the Radiation Assessment Detector (RAD), situated on board the Curiosity rover, conducted measurements of the energetic-particle radiation environment inside the spacecraft. This environment consists mainly of galactic cosmic rays (GCRs), as well as secondary particles created by interactions of these GCRs with the spacecraft. The RAD measurements can serve as a proxy for the radiation environment a human crew would encounter during a transit to Mars, for a given part of the solar cycle, assuming that a crewed vehicle would have comparable shielding. The measurements of radiological quantities made by RAD are important in themselves, and, the same data set allow for detailed analysis of GCR-induced particle spectra inside the spacecraft. This provides important inputs for the evaluation of current transport models used to model the free-space (and spacecraft) radiation environment for different spacecraft shielding and different times in the solar cycle. Changes in these conditions can lead to significantly different radiation fields and, thus, potential health risks, emphasizing the need for validated transport codes. Here, we present the first measurements of charged particle fluxes inside a spacecraft during the transit from Earth to Mars. Using data obtained during the last two month of the cruise to Mars (June 11-July 14, 2012), we have derived detailed energy spectra for low-Z particles stopping in the instrument's detectors, as well as integral fluxes for penetrating particles with higher energies. Furthermore, we analyze the temporal changes in measured proton fluxes during quiet solar periods (i.e., when no solar energetic particle events occurred) over the duration of the transit (December 9, 2011-July 14, 2012) and correlate them with changing heliospheric conditions. PMID- 27662787 TI - Simulated sudden increase in geomagnetic activity and its effect on heart rate variability: Experimental verification of correlation studies. AB - Previous research investigating the potential influence of geomagnetic factors on human cardiovascular state has tended to converge upon similar inferences although the results remain relatively controversial. Furthermore, previous findings have remained essentially correlational without accompanying experimental verification. An exception to this was noted for human brain activity in a previous study employing experimental simulation of sudden geomagnetic impulses in order to assess correlational results that had demonstrated a relationship between geomagnetic perturbations and neuroelectrical parameters. The present study employed the same equipment in a similar procedure in order to validate previous findings of a geomagnetic-cardiovascular dynamic with electrocardiography and heart rate variability measures. Results indicated that potential magnetic field effects on frequency components of heart rate variability tended to overlap with previous correlational studies where low frequency power and the ratio between low and high frequency components of heart rate variability appeared affected. In the present study, a significant increase in these particular parameters was noted during geomagnetic simulation compared to baseline recordings. PMID- 27662786 TI - The effects of short-term hypergravity on Caenorhabditis elegans. AB - As we seek to recognize the opportunities of advanced aerospace technologies and spaceflight, it is increasingly important to understand the impacts of hypergravity, defined as gravitational forces greater than those present on the earth's surface. The nematode Caenorhabditis elegans has been established as a powerful model to study the effects of altered gravity regimens and has displayed remarkable resilience to space travel. In this study, we investigate the effects of short-term and defined hypergravity exposure on C. elegans motility, brood size, pharyngeal pumping rates, and lifespan. The results from this study advance our understanding of the effects of shorter durations of exposure to increased gravitational forces on C. elegans, and also contribute to the growing body of literature on the impacts of altered gravity regimens on earth's life forms. PMID- 27662788 TI - No evidence for an increase in circulatory disease mortality in astronauts following space radiation exposures. AB - Previous analysis has shown that astronauts have a significantly lower standardized mortality ratio for circulatory disease mortality compared to the U.S. population, which is consistent with the rigorous selection process and healthy lifestyles of astronauts, and modest space radiation exposures from past space missions. However, a recent report by Delp et al. estimated the proportional mortality ratio for ages of 55-64 y of Apollo lunar mission astronauts to claim a high risk of cardiovascular disease due to space radiation compared to the U.S. population or to non-flight astronauts. In this Commentary we discuss important deficiencies in the methods and assumptions on radiation exposures used by Delp et al. that we judge cast serious doubt on their conclusions. PMID- 27662789 TI - National survey to evaluate musuloskeletal health in retired professional ballet dancers in the United Kingdom. AB - OBJECTIVES: To explore the musculoskeletal health of retired professional ballet dancers in the United Kingdom (UK). DESIGN: Online national survey. PARTICIPANTS: Retired professional ballet dancers living in the UK. METHODS: The survey explored: what musculoskeletal injuries or diseases are experienced by retired professional ballet dancers; which anatomical regions were affected by musculoskeletal injuries or diseases in retired professional ballet dancers; whether ballet dancers were forced to retire from professional ballet due to musculoskeletal injuries or disease. RESULTS: Forty-six retired ballet dancers responded. Thirty-six percent (n = 17) of respondents reported retiring from ballet due to musculoskeletal injury. The median age when respondents retired from professional ballet was 29 years. The most common issues that caused people to retire were hip and back pain (25%; n = 9 respectively), followed by hamstring injuries, ankle injuries, cervical spine injuries, and anterior knee pain (13% respectively; n = 5). Ninety-one percent (n = 42) reported experiencing muscle and joint pain post-retirement. CONCLUSIONS: Musculoskeletal pain and disease was a problem for respondents in this study. Further investigation is needed to define the problem, so management can be examined. Comparing performance and training regimes to injury rates in professional dancers, and then following these cohorts into retirement, would increase knowledge on this population. PMID- 27662790 TI - Ankle dorsiflexion range of motion influences Lateral Step Down Test scores in individuals with chronic ankle instability. AB - OBJECTIVES: To determine differences in ankle dorsiflexion range of motion (ROM) between three groups of individuals with chronic ankle instability (CAI) based on Lateral Step Down Test quality of movement. The secondary purpose was to quantify the relationship between ankle dorsiflexion ROM and Lateral Step Down Test scores. DESIGN: Descriptive laboratory study. SETTING: University research laboratory. PARTICIPANTS: Fifty-nine participants with CAI. MAIN OUTCOME MEASURES: Differences in ankle dorsiflexion ROM between three Lateral Step Down Test movement quality groups (good, moderate, poor) was determined using an analysis of variance. The relationship between outcome variables was determined using a Spearman rank correlation coefficient. RESULTS: Significantly less ankle dorsiflexion ROM was observed in individuals with poor movement quality (36.0 +/- 6.6 degrees ) compared to good (42.3 +/- 6.4 degrees ). Individuals with moderate movement quality did not have ankle dorsiflexion ROM (39.1 +/- 6.2 degrees ) that was significantly different from either group. There was a negative correlation (r = -0.39) between ankle dorsiflexion ROM and Lateral Step Down Test scores. CONCLUSIONS: Participants in the poor movement quality group had 6 degrees less ankle dorsiflexion ROM than participants in the good movement quality group. While ankle dorsiflexion ROM is associated with Lateral Step Down Test scores additional factors likely contribute to movement dysfunction in individuals with CAI. TRIAL REGISTRY: This trial was registered on ClinicalTrials.gov (NCT01438905). PMID- 27662791 TI - Immune checkpoint blockade: Which switches to hit and how much? PMID- 27662792 TI - Altered circulating T follicular helper cell subsets in patients with psoriasis vulgaris. AB - Circulating T follicular helper (Tfh) cells in the blood are counterparts to conventional Tfh cells in germinal centres. Similarly to conventional Tfh cells, circulating Tfh cells provide helpful signals for B cells. Circulating Tfh cells can be divided into three subpopulations, including Tfh17 (CXCR3-CCR6+), Tfh1 (CXCR3+CCR6-), and Tfh2 (CXCR3-CCR6-) cells, based on differences in CXCR3 and CCR6 expression. Recent studies have demonstrated that alterations in circulating Tfh cell subsets have significant effects on the progression of numerous autoimmune diseases. To address the role of circulating Tfh cells in psoriasis, we used flow cytometry to analyse frequencies of circulating Tfh cell subsets and levels of IL-21 receptor (IL-21R) expression on B cells in 32 patients with psoriasis vulgaris and 13 sex- and age-matched healthy controls. We observed dynamic changes in Tfh17 cell frequency and disease severity in 10 psoriasis patients during a 6-month treatment. Our results demonstrate that the frequency of Tfh17 cells was significantly increased in psoriasis patients and was positively correlated with psoriasis area and severity index (PASI) score, a marker of disease severity (P<0.05). During the follow-up period, the frequencies of Tfh17 cells decreased, and reductions in PASI scores were observed. Moreover, IL-21R expression on B cells was significantly increased in patients with psoriasis vulgaris (P<0.05). Interestingly, IL-21R levels on B cells were correlated with both PASI score and the frequency of Tfh17 cells (P<0.05). In conclusion, this study is the first investigation of the distribution of circulating Tfh subsets in psoriasis. These results deepen our understanding of the immune state of psoriasis patients. Our data also indicate that Tfh17 cells may not be good biomarkers for diagnosing psoriasis but may be potential biomarkers of disease severity in psoriasis. PMID- 27662793 TI - Investigating the addition of collagen and its integrin binding sequence (RGD) to glass polyalkenoate: In terms of material and cellular properties to explore a more biocompatible method of root caries restoration. AB - AIMS: Placement of a restoration to treat root caries disrupts many tissues. There is scope for the restorative material to interact with these to augment reductions in micro leakage afforded by an adhesive restorative material. OBJECTIVES: 1) To investigate the effects of incorporating bioactive molecules into a glass polyalkenoate (GPA) 2) To quantify the changes in physical properties of the material. METHODS: Biocompatibility of the GPA cement (Chemfil Superior, Dentsply De Trey, Konstanz, Germany) in unmodified and modified forms was ascertained using cell culture techniques. The optimum concentration of bioactive components required to promote cell attachment was determined indirectly by quantification and localisation of the fibroblast marker vimentin. The properties of surface hardness, compressive strength and adhesive bond strength were also determined prior to and following addition of the bio additives: collagen type I and a pentapeptide containing Arg-Gly-Asp (RGD). RESULTS: Addition of Type I Collagen (100MUg/ml) and RGD (5mg/ml) to ChemFil Superior had no statistically significant effect upon the compressive strength and bond strength to bovine enamel but significantly (P<0.05) increased the materials shore hardness. The addition of RGD to ChemFil Superior increased most the expression of vimentin, indicating that the cells had become more fibroblastic. This may be indicative of increased synthesis of extracellular matrix macromolecules with the potential to foster adhesion of the modified glass polyalkenoate to distracted gingival tissues. CONCLUSIONS: The results suggest that addition of bioactive molecules to GPA cement for subgingival restorations has potential clinical applications. CLINICAL SIGNIFICANCE: It is possible to envisage that the additions, as described in this paper, could foster the attachment of displaced gingival tissues to GPA restorative materials placed subgingivally where root caries has been treated. This would offer potential to form a seal around the restoration by the attached gingival tissues avoiding a periodontal pocket and depriving residual cariogenic bacteria of a nutrient supply. Further investigation of the effects upon other similar materials of such additions is warranted. PMID- 27662794 TI - Oral health-related quality of life and associated factors in a care-dependent and a care-independent older population. AB - OBJECTIVES: To examine relationships between oral health (OH) factors and general health (GH) factors (including physical, mental, and social health domains), and oral health-related quality of life (OHRQoL) in a care-independent and a care dependent older population. METHODS: Care-independent participants (n=109) were recruited from the Nijmegen dental school; care-dependent participants (n=126) from residential aged care facilities. Data collected included: OHRQoL (Geriatric Oral Health Assessment Index (GOHAI)), age, gender, socioeconomic status, number of teeth and occluding pairs, presence of carious teeth, presence of removable dental prostheses, clinically assessed treatment need (CTN), self-reported GH, and, only for care-dependent participants: care-dependency level and health domain variables: physical, mental (SF-12: Physical and Mental Component Summary scores), and social (ENRICHD social support index). Multiple linear regression analyses were performed to assess the associations with GOHAI scores. RESULTS: Mean GOHAI scores of care-independent (51.6+/-7.4) and care-dependent participants (52.1+/-6.7) did not differ significantly despite considerably worse OH status of the latter. Regression models revealed significant (p<=0.05) associations between GOHAI scores and age, prosthodontic status, and CTN in care independent participants (R2=0.19) and only with CTN in care-dependent participants. (R2=0.09). Self-reported GH was not significantly associated with GOHAI; when substituted by the health domain variables, only social support was significantly associated with GOHAI scores. CONCLUSIONS: GOHAI outcomes are associated with different variables in care-independent and care-dependent older subjects. In care-dependent subjects, GOHAI outcomes are more strongly related to social support than to OH factors or other GH factors. CLINICAL SIGNIFICANCE: OHRQoL outcomes should not be compared across care-dependent and care-independent populations without careful interpretation of these outcomes against specific factors that distinguish such populations, like health factors and living environment. PMID- 27662795 TI - Prolonged Repetitive Head Trauma Induces a Singular Chronic Traumatic Encephalopathy-Like Pathology in White Matter Despite Transient Behavioral Abnormalities. AB - Repetitive mild traumatic brain injury (rmTBI), resulting from insults caused by an external mechanical force that disrupts normal brain function, has been linked to the development of neurodegenerative diseases, such as chronic traumatic encephalopathy and Alzheimer disease; however, neither the severity nor frequency of head injury required to trigger adverse behavioral outcomes is well understood. In this study, the administration of 30 head impacts using two different weights to lightly anesthetized, completely unrestrained mice established a paradigm that simulates the highly repetitive nature of sports- and military-related head injury. As the number of head impacts increases, the time to recover consciousness diminishes; however, both the sensorimotor function and behavioral outcomes of impacted mice evolve during the ensuing weeks. Postmortem analyses reveal robust Alzheimer disease and chronic traumatic encephalopathy like conditions that manifest in a singular manner throughout the white matter concomitant with evidence of chronic oligodendrogenesis. Our data suggest that latency to recover the righting reflex may be an inadequate measure of injury severity and imply that exposure to repeated head impacts may mask the severity of an underlying and developing neuropathologic condition that does not manifest itself until long after head collisions cease. In addition, our data indicate that there is a cumulative and dose-dependent effect of repetitive head impacts that induces the neurobehavioral and neuropathologic outcomes seen in humans with a history of rmTBI. PMID- 27662796 TI - Heme Oxygenase 1 Up-Regulates Glomerular Decay Accelerating Factor Expression and Minimizes Complement Deposition and Injury. AB - Complement-activation controllers, including decay accelerating factor (DAF), are gaining emphasis as they minimize injury in various dysregulated complement activation disorders, including glomerulopathies. Heme oxygenase (HO)-1 overexpression or induction has been shown to attenuate injury in complement dependent models of glomerulonephritis. This study investigated whether up regulation of DAF by heme oxygenase 1 (HO-1) is an underlying mechanism by using Hmox-1-deficient rats (Hmox1+/-; Hmox1-/-) or rats with HO-1 overexpression targeted to glomerular epithelial cells (GECHO-1), which are particularly vulnerable to complement-mediated injury owing to their terminally differentiated nature. Constitutively expressed DAF was decreased in glomeruli of Hmox1-/- rats and augmented in glomeruli of GECHO-1 rats. In GECHO-1 rats with anti-glomerular basement membrane antibody mediated, complement-dependent injury, complement component C3 fragment b (C3b) deposition was reduced, whereas proteinuria was diminished. In glomeruli of wild-type rats, the natural Hmox substrate, hemin, induced glomerular DAF. This effect was attenuated in glomeruli of Hmox1-/- rats and augmented in glomeruli of GECHO-1 rats. Hemin analogues differing in either metal or porphyrin ring functionalities, acting as competitive Hmox-substrate inhibitors, also increased glomerular DAF and reduced C3b deposition after spontaneous complement activation. In the presence of a DAF-blocking antibody, the reduction in C3b deposition was reversed. These observations establish HO-1 as a physiologic regulator of glomerular DAF and identify hemin analogues as inducers of functional glomerular DAF able to minimize C3b deposition. PMID- 27662798 TI - Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p. AB - Pathways of liver fibrosis are controlled by connective tissue growth factor (CCN2). In this study, CCN2 was identified as a target of miR-199a-5p, which was principally expressed in quiescent mouse hepatic stellate cells (HSCs) and directly suppressed production of CCN2. Up-regulated CCN2 expression in fibrotic mouse livers or in activated primary mouse HSCs was associated with miR-199a-5p down-regulation. MiR-199a-5p in quiescent mouse HSCs inhibited the activity of a wild-type CCN2 3' untranslated region (3'-UTR) but not of a mutant CCN2 3'-UTR lacking the miR-199a-5p-binding site. In activated mouse HSCs, CCN2, alpha-smooth muscle actin, and collagen 1(alpha1) were suppressed by a miR-199a-5p mimic, whereas in quiescent mouse HSCs, the inhibited CCN2 3'-UTR activity was blocked by a miR-199a-5p antagomir. CCN2 3'-UTR activity in human HSCs was reduced by a miR-199a-5p mimic. MiR-199a-5p was present at higher levels in exosomes from quiescent versus activated HSCs. MiR-199a-5p-containing exosomes were shuttled from quiescent mouse HSCs to activated mouse HSCs in which CCN2 3'-UTR activity was then suppressed. Exosomes from quiescent HSCs caused miR-199a-5p-dependent inhibition of CCN2, alpha-smooth muscle actin, or collagen 1(alpha1) in activated HSCs in vitro and bound to activated HSCs in vivo. Thus, CCN2 suppression by miR 199a-5p accounts, in part, for low-level fibrogenic gene expression in quiescent HSCs and causes dampened gene expression in activated HSCs after horizontal transfer of miR-199a-5p in exosomes from quiescent HSCs. PMID- 27662800 TI - A new selective fluorescent probe based on tamoxifen. AB - Developing targeted validation probes that can interrogate biology is of interest for both chemists and biologists. The synthesis of suitable compounds provides a means for avoiding the costly labeling of cells with specific antibodies and the bias associated with the interpretation of biological validation experiments. The chemotherapeutic agent, tamoxifen has been routinely used in the treatment of breast cancer for decades. Once metabolized, the active form of tamoxifen (4 hydroxytamoxifen) competes with the binding of estrogens to the estrogen receptors (ER). Its selectivity in ER modulation makes it an ideal candidate for the development of materials to be used as chemical probes. Here we report the synthesis of a fluorescent BODIPY(r)FL conjugate of tamoxifen linked through an ethylene glycol moiety, and present proof-of-principle results in ER positive and ER negative cell lines. Optical microscopy indicates that the fluorescent probe binds selectively to tamoxifen sensitive breast cancer cell lines. The compound showed no affinity for the tamoxifen resistant breast cancer lines. The specificity of the new compound make it a valuable addition to the chemical probe tool kit for estrogen receptors. PMID- 27662801 TI - Unshared binding sites for Bacillus thuringiensis Cry3Aa and Cry3Ca proteins in the weevil Cylas puncticollis (Brentidae). AB - Bacillus thuringiensis Cry3Aa and Cry3Ca proteins have been reported to be toxic against the African sweetpotato pest Cylas puncticollis. In the present work, the binding sites of these proteins in C. puncticollis brush border vesicles suggest the occurrence of different binding sites, but only one of them is shared. Our results suggest that pest resistance mediated by alteration of the shared Cry receptor binding site might not render both Cry proteins ineffective. PMID- 27662799 TI - Long-acting reversible contraceptive acceptability and unintended pregnancy among women presenting for short-acting methods: a randomized patient preference trial. AB - BACKGROUND: Measures of contraceptive effectiveness combine technology and user related factors. Observational studies show higher effectiveness of long-acting reversible contraception compared with short-acting reversible contraception. Women who choose long-acting reversible contraception may differ in key ways from women who choose short-acting reversible contraception, and it may be these differences that are responsible for the high effectiveness of long-acting reversible contraception. Wider use of long-acting reversible contraception is recommended, but scientific evidence of acceptability and successful use is lacking in a population that typically opts for short-acting methods. OBJECTIVE: The objective of the study was to reduce bias in measuring contraceptive effectiveness and better isolate the independent role that long-acting reversible contraception has in preventing unintended pregnancy relative to short-acting reversible contraception. STUDY DESIGN: We conducted a partially randomized patient preference trial and recruited women aged 18-29 years who were seeking a short-acting method (pills or injectable). Participants who agreed to randomization were assigned to 1 of 2 categories: long-acting reversible contraception or short-acting reversible contraception. Women who declined randomization but agreed to follow-up in the observational cohort chose their preferred method. Under randomization, participants chose a specific method in the category and received it for free, whereas participants in the preference cohort paid for the contraception in their usual fashion. Participants were followed up prospectively to measure primary outcomes of method continuation and unintended pregnancy at 12 months. Kaplan-Meier techniques were used to estimate method continuation probabilities. Intent-to-treat principles were applied after method initiation for comparing incidence of unintended pregnancy. We also measured acceptability in terms of level of happiness with the products. RESULTS: Of the 916 participants, 43% chose randomization and 57% chose the preference option. Complete loss to follow-up at 12 months was <2%. The 12-month method continuation probabilities were 63.3% (95% confidence interval, 58.9-67.3) (preference short-acting reversible contraception), 53.0% (95% confidence interval, 45.7-59.8) (randomized short-acting reversible contraception), and 77.8% (95% confidence interval, 71.0-83.2) (randomized long-acting reversible contraception) (P < .001 in the primary comparison involving randomized groups). The 12-month cumulative unintended pregnancy probabilities were 6.4% (95% confidence interval, 4.1-8.7) (preference short-acting reversible contraception), 7.7% (95% confidence interval, 3.3-12.1) (randomized short-acting reversible contraception), and 0.7% (95% confidence interval, 0.0-4.7) (randomized long acting reversible contraception) (P = .01 when comparing randomized groups). In the secondary comparisons involving only short-acting reversible contraception users, the continuation probability was higher in the preference group compared with the randomized group (P = .04). However, the short-acting reversible contraception randomized group and short-acting reversible contraception preference group had statistically equivalent rates of unintended pregnancy (P = .77). Seventy-eight percent of randomized long-acting reversible contraception users were happy/neutral with their initial method, compared with 89% of randomized short-acting reversible contraception users (P < .05). However, among method continuers at 12 months, all groups were equally happy/neutral (>90%). CONCLUSION: Even in a typical population of women who presented to initiate or continue short-acting reversible contraception, long-acting reversible contraception proved highly acceptable. One year after initiation, women randomized to long-acting reversible contraception had high continuation rates and consequently experienced superior protection from unintended pregnancy compared with women using short-acting reversible contraception; these findings are attributable to the initial technology and not underlying factors that often bias observational estimates of effectiveness. The similarly patterned experiences of the 2 short-acting reversible contraception cohorts provide a bridge of generalizability between the randomized group and usual-care preference group. Benefits of increased voluntary uptake of long-acting reversible contraception may extend to wider populations than previously thought. PMID- 27662802 TI - Linking ICF components to outcome measures for orthotic intervention for CMC OA: A systematic review. AB - STUDY DESIGN: Systematic review. INTRODUCTION/PURPOSE: The purpose of this study was to systematically review outcome measures used for assessment of orthotic intervention in the conservative management of thumb carpometacarpal osteoarthritis to determine if they characterize International Classification of Functioning, Disability, and Health (ICF) components. The determinants of patient satisfaction regarding the orthotic intervention were also extracted from the studies. METHODS: A comprehensive literature search was conducted. Outcome measures in the included studies were linked to the ICF. Determinants of patient satisfaction regarding the orthotic intervention were also extracted. RESULTS: Nine studies met inclusion criteria. Eight (47.1%) outcomes were linked to body structures and functions, 8 (47.1%) to activity limitations and participation restrictions, and 1 (5.9%) outcome fell into the nondefinable quality of life category. Four studies assessed patient satisfaction. DISCUSSION/CONCLUSIONS: This systematic review on orthotic intervention for thumb carpometacarpal osteoarthritis found opportunities related to assessment and outcome measures when present studies are linked to the ICF. LEVEL OF EVIDENCE: 2a. PMID- 27662803 TI - Putative new groups of invertebrate water channels based on the snail Helix pomatia L. (Helicidae) MIP protein identification and phylogenetic analysis. AB - Water channel proteins, classified as a family of Membrane Intrinsic Proteins (MIPs) superfamily, enable rapid movement of water and small uncharged molecules through biological membranes. Although water channel proteins are required in several important processes characteristic for the animals, such as osmoregulation, mucus secretion, or defense against desiccation, molluscs, until now, have been very poorly explored in this aspect. Therefore, we decided to study MIPs in Helix pomatia L. applied as a model in studies on terrestrial snail physiology. Our studies consisted in: the snail organ transcriptome sequencing and consecutive bioinformatic analysis of the predicted protein, estimation of the encoding transcript expression (qPCR), investigation of the predicted protein function in the yeast Saccharomyces cerevisiae cells, and the phylogenetic analysis. We identified six water channel proteins, named HpAQP1 to HpAQP6. All of them were proven to transport water, two of them (HpAQP3 and HpAQP4) were also shown to be able to transport glycerol, and other two (HpAQP5 and HpAQP6) to transport H2O2. Phylogenetic analysis indicated that the proteins either fell into aquaporins (HpAQP1, HpAQP2 and HpAQP5) or formed new groups of invertebrate water channel proteins, not described until now, that we suggest to term malacoglyceroporins (HpAQP3 and HpAQP4) and malacoaquaporins (HpAQP6). Thus, the classification of animal water channels based on the vertebrate proteins and including aquaporin, aquaglyceroporin, S-aquaporin and AQP8-type grades does not reflect diversity of these proteins in invertebrates. The obtained results provide important data concerning diversity of water channel protein repertoire in aquatic and terrestrial invertebrates and should also contribute to the improvement of animal water channel classification system. PMID- 27662804 TI - Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms. AB - A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K1 and K2) and the coefficient of viscosity (MU). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach. PMID- 27662805 TI - Permeation of topically applied caffeine from a food by-product in cosmetic formulations: Is nanoscale in vitro approach an option? AB - The aim of the present work was to develop and evaluate the potential of nanostructured lipid carriers associated with caffeine extracted from Coffee Silverskin (NLC-CS), a food by-product, as a new possible topical therapy of cellulitis. Caffeine gain increasing research interest due to their cosmetic potential, particularly in gynoid lipodystrophy, commonly known as cellulite. NLC CS were prepared via double emulsion technique using polysorbate 60 as surfactant and characterized for their morphology, particle size, zeta potential, association encapsulation and stability. The in vitro skin permeation studies were performed on Franz diffusion cells using pig skin ear as permeation membrane and the optimized formulation was compared with a hydroalcoholic solution of Coffee silverskin (CS) extract. NLC-CS were within the nanosized range (~200nm), with a low polydispersity index (<0.25) and zeta potential values around -30Mv, presenting storage stability up to 180days at 25 degrees C/65% relative humidity (RH) and 40 degrees C/75% RH. The association efficiency (AE) of caffeine was about 30% at production time and after storage period. Cryo-SEM images confirmed the spherical shape of NLC-CS. The in vitro skin permeation study demonstrated that NLC-CS had a similar skin permeation profile when compared to caffeine in CS extract. PMID- 27662806 TI - Characterization of candidate intermediates in the Black Box of the ecdysone biosynthetic pathway in Drosophila melanogaster: Evaluation of molting activities on ecdysteroid-defective larvae. AB - Early steps of the biosynthetic pathway of the insect steroid hormone ecdysone remains the "Black Box" wherein the characteristic ecdysteroid skeleton is built. 7-Dehydrocholesterol (7dC) is the precursor of uncharacterized intermediates in the Black Box. The oxidation step at C-3 has been hypothesized during conversion from 7dC to 3-oxo-2,22,25-trideoxyecdysone, yet 3-dehydroecdysone is undetectable in some insect species. Therefore, we first confirmed that the oxidation at C-3 occurs in the fruitfly, Drosophila melanogaster using deuterium-labeled cholesterol. We next investigated the molting activities of candidate intermediates, including oxidative products of 7dC, by feeding-rescue experiments for Drosophila larvae in which an expression level of a biosynthetic enzyme was knocked down by the RNAi technique. We found that the administration of cholesta 4,7-dien-3-one (3-oxo-Delta4,7C) could overcome the molting arrest of ecdysteroid defective larvae in which the expression level of neverland was reduced. However, feeding 3-oxo-Delta4,7C to larvae in which the expression levels of shroud and Cyp6t3 were reduced inhibited molting at the first instar stage, suggesting that this steroid could be converted into an ecdysteroid-antagonist in loss of function studies of these biosynthetic enzymes. Administration of the highly conjugated cholesta-4,6,8(14)-trien-3-one, oxidized from 3-oxo-Delta4,7C, did not trigger molting of ecdysteroid-defective larvae. These results suggest that an oxidative product derived from 7dC is converted into ecdysteroids without the formation of this stable conjugated compound. We further found that the 14alpha hydroxyl moiety of Delta4-steroids is required to overcome the molting arrest of larvae in loss of function studies of Neverland, Shroud, CYP6T3 or Spookier, suggesting that oxidation at C-14 is indispensable for conversion of these Delta4 steroids into ecdysteroids via 5beta-reduction. PMID- 27662807 TI - Structure-activity relationships of fluorinated dendrimers in DNA and siRNA delivery. AB - : Fluorinated dendrimers have shown great promise in gene delivery due to their high transfection efficacy and low cytotoxicity, however, the structure-activity relationships of these polymers still remain unknown. Herein, we synthesized a library of fluorinated dendrimers with different dendrimer generations and fluorination degrees and investigated their behaviors in both DNA and siRNA delivery. The results show that fluorination significantly improves the transfection efficacy of G4-G7 polyamidoamine dendrimers in DNA and siRNA delivery. Fluorination on generation 5 dendrimer yields the most efficient polymers in gene delivery, and the transfection efficacy of fluorinated dendrimers depends on fluorination degree. All the fluorinated dendrimers cause minimal toxicity on the transfected cells at their optimal transfection conditions. This study provides a general and facile strategy to prepare high efficient and low cytotoxic gene carriers based on fluorinated polymers. STATEMENT OF SIGNIFICANCE: The structure-activity relationships of fluorinated dendrimers in gene delivery is still unknown and the behavior of fluorinated dendrimers in siRNA delivery has not yet been investigated. Herein, we synthesized a library of fluorinated PAMAM dendrimers with different dendrimer generations and fluorination degrees and investigated their behaviors in both DNA and siRNA delivery. The results clearly indicate that fluorination significantly improves the transfection efficacy of dendrimers in both DNA and siRNA delivery without causing additional toxicity. G5 PAMAM dendrimer is best scaffold to synthesize fluorinated dendrimers and the transfection efficacy of fluorinated dendrimers depends on fluorination degree. This systematic study provides a general and facile strategy to prepare high efficient and low cytotoxic gene carriers based on fluorinated polymers. PMID- 27662808 TI - Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual modal targeted imaging and chemotherapy. AB - : Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of FA GdNS@CQDs. FA-GdNS@CQDs enhanced the MR response as compared to that for commercial Gd-DTPA. The targeting capabilities of FA-GdNS@CQDs were confirmed in HeLa and HepG2 cells using in vitro fluorescence and MR dual modality imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the FA GdNS@CQDs forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. Importantly, the prepared FA-GdNS@CQDs-DOX showed a high quantity of doxorubicin loading capacity (about 80%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the FA-GdNS@CQDs were observed by confocal laser scanning microscopy. We also successfully demonstrated in vivo fluorescence bio imaging of the FA-GdNS@CQDs, using zebrafish as an animal model. STATEMENT OF SIGNIFICANCE: In this manuscript, we reported a facial, rapid, and environmental friendly method to fabricate hetero atoms including gadolinium, nitrogen, and sulfur doped multi-functional magnetofluorescent carbon quantum dots (GdNS@CQDs) nanocomposite. These multifunctional GdNS@CQDs were conjugated with a folic acid for targeting dual modal fluorescence/magnetic resonance imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the nanocomposite forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. We have developed GdNS@CQDs with integrated functions for simultaneous in vitro cell imaging, targeting, and pH-sensitive controlled drug release in HeLa cells. Furthermore, we successfully demonstrated the use of this material for in vivo fluorescence imaging, using zebrafish as an animal model. PMID- 27662810 TI - Proteostasis and SUMO in the heart. AB - Heart proteostasis relies on a complex and integrated network of molecular processes surveilling organ performance under physiological and pathological conditions. For this purpose, cardiac cells depend on the correct function of their proteolytic systems, such as the ubiquitin-proteasome system (UPS), autophagy and the calpain system. Recently, the role of protein SUMOylation (an ubiquitin-like modification), has emerged as important modulator of cardiac proteostasis, which will be the focus of this review. PMID- 27662811 TI - Application of an epitope-based allocation system in pediatric kidney transplantation. AB - Donor-recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope-based allocation approach to prospectively exclude donors with high level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m2 , no episodes of rejection, and time to transplant 6.55 months. HLA-A, HLA-B, HLA-DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope-based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow-up and larger numbers, but has the potential to reduce anti-HLA sensitization and improve both graft survival and opportunities for future retransplantation. PMID- 27662812 TI - Usefulness of plasma neutrophil gelatinase-associated lipocalin concentration for predicting the severity and mortality of patients with community-acquired pneumonia. AB - BACKGROUND: The usefulness of plasma neutrophil gelatinase-associated lipocalin (NGAL) concentration for predicting the outcome of community-acquired pneumonia (CAP) is unclear. We evaluated the prognostic value of plasma NGAL concentration for predicting disease severity in comparison with other widely used biological markers of inflammation in patients with CAP. METHODS: NGAL, procalcitonin, and C reactive protein concentrations were measured in 362 patients with CAP, who were followed for up to 30days. The Pneumonia Severity Index (PSI) and CURB-65 score were obtained for all patients. RESULTS: The median plasma NGAL concentration increased with CAP severity classified according to the PSI. Plasma NGAL concentration was higher in nonsurvivors than in survivors. The AUC for predicting mortality was highest for NGAL concentration (0.871), followed by that for PSI (0.865) and procalcitonin concentration (0.744). Multivariable logistic regression analysis showed that plasma NGAL concentration was an independent predictor of hospital mortality in CAP patients. Plasma NGAL concentration correlated positively with C-reactive protein and procalcitonin concentrations, CURB-65 score, and PSI. CONCLUSIONS: Plasma NGAL concentration is a valuable biological marker in the assessment of the severity and prediction of the prognosis of patients with CAP in the emergency department. PMID- 27662809 TI - Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen. AB - : Fibrin is a major component of the provisional extracellular matrix formed during tissue repair following injury, and enables cell infiltration and anchoring at the wound site. Macrophages are dynamic regulators of this process, advancing and resolving inflammation in response to cues in their microenvironment. Although much is known about how soluble factors such as cytokines and chemokines regulate macrophage polarization, less is understood about how insoluble and adhesive cues, specifically the blood coagulation matrix fibrin, influence macrophage behavior. In this study, we observed that fibrin and its precursor fibrinogen elicit distinct macrophage functions. Culturing macrophages on fibrin gels fabricated by combining fibrinogen with thrombin stimulated secretion of the anti-inflammatory cytokine, interleukin-10 (IL-10). In contrast, exposure of macrophages to soluble fibrinogen stimulated high levels of inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Macrophages maintained their anti-inflammatory behavior when cultured on fibrin gels in the presence of soluble fibrinogen. In addition, adhesion to fibrin matrices inhibited TNF-alpha production in response to stimulation with LPS and IFN-gamma, cytokines known to promote inflammatory macrophage polarization. Our data demonstrate that fibrin exerts a protective effect on macrophages, preventing inflammatory activation by stimuli including fibrinogen, LPS, and IFN-gamma. Together, our study suggests that the presentation of fibrin(ogen) may be a key switch in regulating macrophage phenotype behavior, and this feature may provide a valuable immunomodulatory strategy for tissue healing and regeneration. STATEMENT OF SIGNIFICANCE: Fibrin is a fibrous protein resulting from blood clotting and provides a provisional matrix into which cells migrate and to which they adhere during wound healing. Macrophages play an important role in this process, and are needed for both advancing and resolving inflammation. We demonstrate that culture of macrophages on fibrin matrices exerts an anti inflammatory effect, whereas the soluble precursor fibrinogen stimulates inflammatory activation. Moreover, culture on fibrin completely abrogates inflammatory signaling caused by fibrinogen or known inflammatory stimuli including LPS and IFN-gamma. Together, these studies show that the presentation of fibrin(ogen) is important for regulating a switch between macrophage pro- and anti-inflammatory behavior. PMID- 27662813 TI - A further cautionary tale for interpretation of external quality assurance results (EQA): Commutability of EQA materials for point-of-care glucose meters. PMID- 27662814 TI - Interlaboratory analytical comparison of fatty acid concentrations in serum or plasma. AB - BACKGROUND: There are a large number of clinical studies focusing on the measurement of individual fatty acids in serum or plasma; however, few studies have focused on the interlaboratory comparisons of these measurements. The National Institutes of Standards and Technology (NIST), in collaboration with the National Institutes of Health Office of Dietary Supplements (NIH-ODS) and the Centers for Disease Control and Prevention (CDC), has initiated a quality assurance program for assessing and improving the comparability of individual fatty acid measurements in serum and plasma. METHODS: This is a performance-based study so participants are encouraged to use their laboratory's methods for the quantification of the individual fatty acids that they typically measure in the unknown serum or plasma samples along with a control material. The control materials used to date are SRM 1950 Metabolites in Human Plasma and SRM 2378 Fatty Acids in Frozen Human Serum. RESULTS: To date, two studies of the Fatty Acid Quality Assurance Program (FAQAP) have been completed with 11 and 14 participants, respectively. The agreement among the laboratories for individual fatty acids was within 20% for 70% of the data submitted. Laboratories were also requested to run triplicate analyses for each unknown sample. The precision of the individual laboratory data was generally good, with relative standard deviations <20%. CONCLUSIONS: The results from the first two exercises indicate the need for additional assessment of the comparability among laboratories doing these measurements. Future studies will be conducted with the goals of increasing the number of participating laboratories, increasing awareness of the need to use control materials, and improving the comparability among laboratories. PMID- 27662815 TI - The Italian multicentre dosimetric study for lesion dosimetry in 223Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria. AB - PURPOSE: The aims of this work were to explore patient eligibility criteria for dosimetric studies in 223Ra therapy and evaluate the effects of differences in gamma camera calibration procedures into activity quantification. METHODS: Calibrations with 223Ra were performed with four gamma cameras (3/8-inch crystal) acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air by varying activity, source detector distance, and source diameter. Transmission curves were measured for attenuation/scatter correction with the pseudo-extrapolation number method, varying the experimental setup. 223Ra images of twenty-five patients (69 lesions) were acquired to study the lesions visibility. Univariate ROC analysis was performed considering visible/non visible lesions on 223Ra images as true positive/true negative group, and using as score value the lesion/soft tissue contrast ratio (CR) derived from 99mTc-MDP WB scan. RESULTS: Sensitivity was nearly constant varying activity and distance (maximum s.d.=2%). Partial volume effects were negligible for object area ?960mm2. Transmission curve measurements are affected by experimental setup and source size, leading to activity quantification errors up to 20%. The ROC analysis yielded an AUC of 0.972 and an optimal threshold of CR of 10, corresponding to an accuracy of 92%. CONCLUSION: The minimum calibration protocol requires sensitivity and transmission curve measurements varying the object size, performing a careful procedure standardisation. Lesions with 99mTc-MDP CR higher than 10, not overlapping the GI tract, are generally visible on 223Ra images acquired at 24h after the administration, and possibly eligible for dosimetric studies. PMID- 27662816 TI - Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. AB - The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-alpha hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH)2D3, especially in muscle and pancreatic beta cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and (G) relative paucity of rigorous clinical data on the effects of vitamin D sufficiency on non-calcium endpoints. Although a large number of observational studies support improving T2D, insulin resistance, obesity, and metabolic syndrome with vitamin D adequacy, there is a lack of conclusive evidence from randomized control clinical trials that, these disorders are prevented following optimization of serum levels of 25(OH)D. However, none of the currently conducted clinical studies would resolve these issues. Thus, specifically designed, new clinical studies are needed to be conducted in well-defined populations, following normalizing the serum vitamin D levels in vitamin D deficient prediabetes subjects, to test the hypothesis that hypovitaminosis D worsens these disorders and correction would alleviate it. PMID- 27662817 TI - Non-musculoskeletal benefits of vitamin D. AB - The aim of this study is to determine and critically evaluate the plausible relationships of vitamin D with extra-skeletal tissues in humans. Severe vitamin D deficiency results in rickets in children and osteomalacia in adults; these beneficial effects in the musculoskeletal system and certain physiological functions are well understood. Nevertheless, mounting reports support additional beneficial effects of vitamin D, outside the musculoskeletal system. This review explores the recent advances in knowledge about the non-skeletal effects of vitamin D. Peer-reviewed papers were extracted from research databases using key words, to assess correlations between vitamin D and extra-skeletal diseases and conditions. As per the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA); general interpretations of results are included; taking into consideration the broader evidence and implications. This review summarizes current knowledge of the effects of vitamin D status on extra-skeletal tissues with special attention given to relationships between vitamin D status and various diseases commonly affecting adults; the effects of intervention with vitamin D and exposure to sunlight. Evidence suggests that vitamin D facilitates the regulation of blood pressure; and cardiac; endothelial; and smooth muscle cell functions; playing an important role in cardiovascular protection. In addition; 1,25(OH)2D improves immunity; subdues inflammation; and reduces the incidence and severity of common cancers; autoimmune diseases and infectious diseases. Almost all adequately powered; epidemiological and biological studies that use; adequate doses of vitamin D supplementation in D-deficient populations have reported favorable outcomes. These studies have concluded that optimizing 25(OH)D status improves the functionality of bodily systems; reduces comorbidities; improves the quality of life; and increases survival. Although accumulating evidence supports biological associations of vitamin D sufficiency with improved physical and mental functions; no definitive evidence exists from well-designed; statistically powered; randomized controlled clinical trials. Nevertheless, most studies point to significant protective effects of vitamin D in humans when the minimum 25(OH)D serum level exceeds 30ng/mL and is maintained throughout the year. PMID- 27662819 TI - Risk factors of infant anemia in the perinatal period. AB - BACKGROUND: Infants are at particular risk of iron-deficiency anemia. We investigated changes in the blood count of the mother and infant as well as the relationship between them and the relationship between infant nutrition method and infant anemia. METHODS: This retrospective cohort study included healthy neonates born between August 2011 and July 2014 at St Luke's International Hospital, Tokyo, Japan. Data from maternal blood samples obtained during late pregnancy and those of infants obtained at birth and at the age of 3, 6, and 9 months were analyzed. Using multivariate logistic regression, we investigated nutrition methods, maternal anemia, and other clinically relevant parameters that were potential risk factors for infant anemia. RESULTS: In total, data for 3472 infants and their mothers were analyzed. Nutrition method was the most significant risk factor for infant anemia, with risk of future anemia decreasing in the following order: exclusive breast-feeding, partial breast-feeding, and formula feeding. Furthermore, low umbilical cord blood hemoglobin led to a tendency toward anemia in the child. CONCLUSION: Infant nutrition method was the most significant factor related to anemia in late infancy. Infants with low umbilical cord blood hemoglobin are more likely to develop anemia in late infancy. PMID- 27662818 TI - Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab. AB - AIM: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti cetuximab IgE levels (<=29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. RESULTS: Of the 301 assessable patients (mean age: 60.9 +/- 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). CONCLUSIONS: Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs. PMID- 27662820 TI - Advanced Glycation Endproducts Impair Endothelial Progenitor Cell Migration and Homing via Syndecan 4 Shedding. AB - Endothelial progenitor cells (EPCs) are a subtype of bone marrow-derived progenitor cells. Stromal cell-derived factor 1 (SDF-1)-mediated EPC mobilization from bone marrow to areas of ischemia plays an important role in angiogenesis. Previous studies have reported that advanced glycation endproducts (AGEs), which are important mediators of diabetes-related vascular pathology, may impair EPC migration and homing, but the mechanism is unclear. Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan receptor on the cell surface, involved in SDF-1-dependent cell migration. The extracellular domain of synd4 (ext-synd4) is shed in the context of acute inflammation, but the shedding of ext-synd4 in response to AGEs is undefined. Here we investigated changes in ext-synd4 on EPCs in response to AGEs, focusing on the influence of impaired synd4 signaling on EPC migration and homing. We found decreased full length and increased residue of synd4 in cells incubated with AGEs, with concomitant increase in the soluble fragment of ext-synd4 in the cell medium. EPCs from patients with type 2 diabetes expressed less ext-synd4 as assessed by Western blotting. Flow cytometry analysis showed less ext-synd4 on circulating CD34+ peripheral blood mononuclear cells, of which EPCs form a subgroup. We then explored the role of synd4 in EPC migration and homing. Impaired migration of synd4-deficient EPCs was observed by a 2D chemotaxis slide. Furthermore, poor homing of synd4-/- EPCs was observed in a mouse model of lower limb ischemia. This study demonstrates that the shedding of synd4 from EPCs plays a key role in AGE-mediated dysfunction of EPC migration and homing. Stem Cells 2017;35:522-531. PMID- 27662821 TI - The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits. AB - OBJECTIVE: To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects. DESIGN: IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT PCR), respectively. RESULTS: Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction. CONCLUSION: Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF 1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation. PMID- 27662822 TI - The anti-adipogenic effect of peripheral blood mononuclear cells is absent with PCSK9 loss-of-function variants. AB - OBJECTIVE: To determine the effect of (1) an oral fat load and (2) pro-protein convertase subtilisin/kexin type (PCSK) 9 loss-of-function (LOF) variant status on the ability of peripheral blood mononuclear cells (PBMC) to inhibit human adipogenesis. METHODS: PBMC from subjects with one or more PCSK9 LOF variants versus non-variant controls were compared in the fasting state and after an oral fat load. RESULTS: Fasting triglyceride (TG) levels were lower in the LOF variant versus non-variant group but rose to the same level after the oral fat load. Conditioned medium from PBMC was obtained in fasting (PBMC-CM-F) and 4-h postprandial (PBMC-CM-PP) states. PBMC-CM-PP from non-variant controls inhibited adipogenesis of human preadipocytes more than did PBMC-CM-F. In contrast, PBMC-CM F or -PP from PCSK9 LOF variant subjects had no effect on adipogenesis. After the oral fat load, PBMC from PCSK9 LOF variant subjects showed significant increases in mRNA levels of interleukin-1beta, tumor necrosis factor-alpha, sterol regulatory element binding protein-1c, CD36, and monocyte chemoattractant protein 1 (MCP-1), only MCP-1 mRNA levels increased in PBMC from non-variant controls. CONCLUSIONS: The absence of anti-adipogenic action of PBMC from PCSK9 LOF variant subjects points to a novel role for PCSK9 in PBMC-adipose cell interactions. PMID- 27662823 TI - Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy. AB - Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. (c) 2016 BioFactors, 43(2):187-194, 2017. PMID- 27662824 TI - An anthropological approach to teach and evaluate cultural competence in medical students - the application of mini-ethnography in medical history taking. AB - PURPOSE: To use mini-ethnographies narrating patient illness to improve the cultural competence of the medical students. METHODS: Between September 2013 and June 2015, all sixth-year medical students doing their internship at a medical center in eastern Taiwan were trained to write mini-ethnographies for one of the patients in their care. The mini-ethnographies were analyzed by authors with focus on the various aspects of cultural sensitivity and a holistic care approach. RESULTS: Ninety-one students handed in mini-ethnographies, of whom 56 were male (61.5%) and 35 were female (38.5%). From the mini-ethnographies, three core aspects were derived: 1) the explanatory models and perceptions of illness, 2) culture and health care, and 3) society, resources, and health care. Based on the qualities of each aspect, nine secondary nodes were classified: expectations and attitude about illness/treatment, perceptions about their own prognosis in particular, knowledge and feelings regarding illness, cause of illness, choice of treatment method (including traditional medical treatments), prejudice and discrimination, influences of traditional culture and language, social support and resources, and inequality in health care. CONCLUSIONS: Mini-ethnography is an effective teaching method that can help students to develop cultural competence. It also serves as an effective instrument to assess the cultural competence of medical students. PMID- 27662825 TI - Addressing Culture, Gender, and Power with Asian American Couples: Application of Socio-Emotional Relationship Therapy. AB - Asian Americans juggle the intersections of multiple social identities and societal discourses as they respond to experiences of immigration, marginalization, and patriarchy, integrate collectivist and individualistic family values, and form families and intimate relationships. In this study we examine what we have learned as we apply Socio-Emotional Relationship Therapy (SERT) with heterosexual couples of Asian heritage. SERT begins with sociocultural attunement and the assumption that relationships should mutually support each partner. Drawing on case examples, we illustrate how we practice sociocultural attunement as couples respond to the relational processes that comprise the Circle of Care (mutual influence, vulnerability, attunement, and shared relational responsibility). We emphasize three key socioemotional themes that intersect with gender: (1) intangible loss; (2) quiet fortitude/not burdening others; and (3) duty to the family. PMID- 27662826 TI - Associations between sarcoidosis clinical course and ANXA11 rs1049550 C/T, BTNL2 rs2076530 G/A, and HLA class I and II alleles. AB - BACKGROUND: A genetic background may be responsible for the different clinical courses in sarcoidosis. We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions. METHODS: We studied 138 unrelated Caucasian sarcoidosis patients (78 women, 56.5%; mean age, 37.2 +/- 12.1 years). Disease that persisted after 2 years was considered chronic. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays. HLA class I/II alleles were typed using PCR sequence-specific primers. RESULTS: Sixty-six patients experienced disease resolution and 72 (52%) developed chronic disease. Comparison of rs1049550 and rs2076530 allele frequencies showed no significant differences. Only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < .01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution. No significant interactions were found in any of the logistic regression analyses. CONCLUSIONS: In this population of Caucasian patients with sarcoidosis, only DRB1*03 was associated with disease resolution after 2 years' follow-up, with no significant interactions found for susceptibility gene SNPs ANXA11 rs1049550 or BTNL2 rs2076530. PMID- 27662828 TI - Generation and characterization of a novel transgenic mouse harboring conditional nuclear factor-kappa B/RelA knockout alleles. AB - BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of RelA leads to massive apoptosis of liver hepatocytes and death in utero. To study the role of RelA in physiology and in disease states in a manner that circumvents this embryonic lethal phenotype, we have generated a mouse with RelA conditional knockout (CKO) alleles containing loxP sites that are deleted by activated Cre recombinase. RESULTS: We demonstrate that RelACKO/CKO mice are fertile, do not display any developmental defects and can be crossed with Cre-expressing mice to delete RelA in a temporal, tissue-specific manner. Our mating of RelACKO/CKO mice with Zp3-Cre transgenic led to embryonic lethality of RelA-deficient embryos. In contrast, mating of RelACKO/CKO mice with Col1alpha2-CreER mice allowed for the generation of double transgenics which could be stimulated with tamoxifen to induce fibroblast-specific RelA deletion in adulthood. CONCLUSIONS: Based on our collective data, we conclude that this novel RelACKO/CKO mouse allows for efficient deletion of RelA in a tissue-specific manner. This RelACKO/CKO mouse will be an invaluable tool for deciphering the mechanistic roles of RelA in various cells and tissues during development and in disease. PMID- 27662827 TI - Barriers and facilitators to the implementation of orthodontic mini implants in clinical practice: a systematic review. AB - BACKGROUND: Numerous surveys have shown that orthodontic mini implants (OMIs) are underused in clinical practice. To investigate this implementation issue, we conducted a systematic review to (1) identify barriers and facilitators to the implementation of OMIs for all potential stakeholders and (2) quantify these implementation constructs, i.e., record their prevalence. We also recorded the prevalence of clinicians in the eligible studies that do not use OMIs. METHODS: Methods were based on our published protocol. Broad-spectrum eligibility criteria were defined. A barrier was defined as any variable that impedes or obstructs the use of OMIs and a facilitator as any variable that eases and promotes their use. Over 30 databases including gray literature were searched until 15 January 2016. The Joanna Briggs Institute tool for studies reporting prevalence and incidence data was used to critically appraise the included studies. Outcomes were qualitatively synthesized, and meta-analyses were only conducted when pre-set criteria were fulfilled. Three reviewers conducted all research procedures independently. We also contacted authors of eligible studies to obtain additional information. RESULTS: Three surveys fulfilled the eligibility criteria. Seventeen implementation constructs were identified in these studies and were extracted from a total of 165 patients and 1391 clinicians. Eight of the 17 constructs were scored by more than 50 % of the pertinent stakeholders. Three of these constructs overlapped between studies. Contacting of authors clarified various uncertainties but was not always successful. Limitations of the eligible studies included (1) the small number of studies; (2) not defining the research questions, i.e., the primary outcomes; (3) the research design (surveys) of the studies and the exclusive use of closed-ended questions; (4) not consulting standards for identifying implementation constructs; (5) the lack of pilot testing; (6) high heterogeneity; (7) the risk of reporting bias; and (8) additional shortcomings. Meta-analyses were not possible because of these limitations. Two eligible studies found that respectively 56.3 % (952/1691) and 40.16 % (439/1093) of clinicians do not use OMIs. CONCLUSIONS: Notwithstanding the limitations of the eligible studies, their findings were important because (1) 17 implementation constructs were identified of which 8 were scored by more than 50 % of the stakeholders; (2) the various shortcomings showed how to improve on future implementation studies; and (3) the underuse of OMIs in the selected studies and in the literature demonstrated the need to identify, quantify, and address implementation constructs. Prioritizing of future research questions on OMIs with all pertinent stakeholders is an important first step and could redirect research studies on OMIs towards implementation issues. Patients, clinicians, researchers, policymakers, insurance companies, implant companies, and research sponsors will all be beneficiaries. PMID- 27662829 TI - In the Information Age, do dementia caregivers get the information they need? Semi-structured interviews to determine informal caregivers' education needs, barriers, and preferences. AB - BACKGROUND: Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. METHODS: We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important themes. RESULTS: We interviewed 19 women, 8 men; mean age 58.5 years; most adult children (15) or spouses (8) of the care recipient. Dementia symptoms often developed insidiously, with delayed disease acknowledgement and caregiver self-identification. While memory loss was common, behavioral symptoms were most troublesome, often initially unrecognized as disease indicators. Emerging themes: 1.) Barriers to seeking information often result from knowledge gaps, rather than reluctance to assume the caregiver role; 2.) Most caregivers currently receive insufficient information. Caregivers are open to many information sources, settings, and technologies, including referrals to other healthcare professionals, print material, and community and internet resources, but expect the primary care provider (PCP) to recommend, endorse, and guide them to specific sources. CONCLUSIONS: These findings replicated and expanded on results from previous quantitative surveys and, importantly, revealed a previously unrecognized essential factor: despite receiving insufficient information, caregivers place critical value on their relationship with care recipient PCPs to receive recommendations, guidance and endorsement to sources of caregiving information. Implications include: 1.) Greater public education is needed to help caregivers identify and describe diverse cognitive, functional and behavioral symptoms that lead to dementia, and recognize the benefits of early detection in accessing information regarding multi-modality management and care; 2.) Improved methods are needed for PCPs to detect and manage cognitive and behavioral changes, as well as mechanisms that facilitate the busy PCP, either directly or via referral, to provide caregiver information, education, support, and services. The critical relationship between caregivers and PCPs should not be circumvented but should be facilitated to provide more effective guidance regarding dementia caregiver needs. PMID- 27662831 TI - Difficulties experienced by migrant physicians working in German hospitals: a qualitative interview study. AB - BACKGROUND: With Germany facing a shortage of doctors, hospitals have been increasingly recruiting physicians from abroad. Studies in other countries have shown that migrant physicians experience various difficulties in their work, which might impact the quality of patient care, physician job satisfaction, and, accordingly, retention. The experiences of migrant doctors in Germany have not been systematically studied so far and will likely differ from experiences migrant physicians make in other contexts. A thorough understanding of challenges faced by this group, however, is needed to develop adequate support structures-as required by the WHO Global Code of Practice on the International Recruitment of Health Personnel. METHODS: A qualitative study was conducted to give an overview of the multifaceted difficulties migrant physicians might face in German hospitals. Twenty semi-structured interviews with foreign-born and foreign trained physicians were conducted in German. Participants were recruited via the State Chambers of Physicians and snowballing based on a maximum variation sampling strategy varying purposefully by source country and medical specialty. The interviews were recorded, transcribed verbatim, and analysed using qualitative content analysis. RESULTS: Participants described difficulties relating to healthcare institutions, own competencies, and interpersonal interactions. Participants experienced certain legal norms, the regulation of licensure and application for work, and the organization of the hospital environment as inadequate. Most struggled with their lack of setting-specific (language, cultural, clinical, and system) knowledge. Furthermore, behaviour of patients and co-workers was perceived as discriminating or inadequate for other reasons. CONCLUSIONS: This is the first study to describe the broad range of issues migrant physicians experience in Germany. Based on this information, institutional actors should devise support structures to ensure quality of care, physician wellbeing, and retention. For example, training opportunities should be offered where needed to support acquisition of setting-specific knowledge. Discrimination experienced by participants calls for better diversity management as a leadership task in healthcare institutions. Misinformation practices in recruitment could be managed by a voluntary code of ethical conduct. Further research is necessary to identify strategies that adequately address diverging normative positions between migrant health personnel and their patients and colleagues. PMID- 27662830 TI - Dying among older adults in Switzerland: who dies in hospital, who dies in a nursing home? AB - BACKGROUND: Institutional deaths (hospitals and nursing homes) are an important issue because they are often at odds with patient preference and associated with high healthcare costs. The aim of this study was to examine deaths in institutions and the role of individual, regional, and healthcare supply characteristics in explaining variation across Swiss Hospital Service Areas (HSAs). METHODS: Retrospective study of individuals >=66 years old who died in a Swiss institution (hospital or nursing homes) in 2010. Using a two-level logistic regression analysis we examined the amount of variation across HSAs adjusting for individual, regional and healthcare supply measures. The outcome was place of death, defined as death in hospital or nursing homes. RESULTS: In 2010, 41,275 individuals >=66 years old died in a Swiss institution; 54 % in nursing homes and 46 % in hospitals. The probability of dying in hospital decreased with increasing age. The OR was 0.07 (95 % CI: 0.05-0.07) for age 91+ years compared to those 66 70 years. Living in peri-urban areas (OR = 1.06 95 % CI: 1.00-1.11) and French speaking region (OR = 1.43 95 % CI: 1.22-1.65) was associated with higher probability of hospital death. Females had lower probability of death in hospital (OR = 0.54 95 % CI: 0.51-0.56). The density of ambulatory care physicians (OR = 0.81 95 % CI: 0.67-0.97) and nursing homes beds (OR = 0.67 95 % CI: 0.56-0.79) was negatively associated with hospital death. The proportion of dying in hospital varied from 38 % in HSAs with lowest proportion of hospital deaths to 60 % in HSAs with highest proportion of hospital deaths (1.6-fold variation). CONCLUSIONS: We found evidence for variation across regions in Switzerland in dying in hospital versus nursing homes, indicating possible overuse and underuse of end of life (EOL) services. PMID- 27662832 TI - Nested coevolutionary networks shape the ecological relationships of ticks, hosts, and the Lyme disease bacteria of the Borrelia burgdorferi (s.l.) complex. AB - BACKGROUND: The bacteria of the Borrelia burgdorferi (s.l.) (BBG) complex constitute a group of tick-transmitted pathogens that are linked to many vertebrate and tick species. The ecological relationships between the pathogens, the ticks and the vertebrate carriers have not been analysed. The aim of this study was to quantitatively analyse these interactions by creating a network based on a large dataset of associations. Specifically, we examined the relative positions of partners in the network, the phylogenetic diversity of the tick's hosts and its impact on BBG circulation. The secondary aim was to evaluate the segregation of BBG strains in different vectors and reservoirs. RESULTS: BBG circulates through a nested recursive network of ticks and vertebrates that delineate closed clusters. Each cluster contains generalist ticks with high values of centrality as well as specialist ticks that originate nested sub networks and that link secondary vertebrates to the cluster. These results highlighted the importance of host phylogenetic diversity for ticks in the circulation of BBG, as this diversity was correlated with high centrality values for the ticks. The ticks and BBG species in each cluster were not significantly associated with specific branches of the phylogeny of host genera (R 2 = 0.156, P = 0.784 for BBG; R 2 = 0.299, P = 0.699 for ticks). A few host genera had higher centrality values and thus higher importance for BBG circulation. However, the combined contribution of hosts with low centrality values could maintain active BBG foci. The results suggested that ticks do not share strains of BBG, which were highly segregated among sympatric species of ticks. CONCLUSIONS: We conclude that BBG circulation is supported by a highly redundant network. This network includes ticks with high centrality values and high host phylogenetic diversity as well as ticks with low centrality values. This promotes ecological sub networks and reflects the high resilience of BBG circulation. The functional redundancy in BBG circulation reduces disturbances due to the removal of vertebrates as it allows ticks to fill other biotic niches. PMID- 27662833 TI - DNA in serum extracellular vesicles is stable under different storage conditions. AB - BACKGROUND: Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, can be secreted by most cell types and released in perhaps all biological fluids. EVs contain multiple proteins, specific lipids and several kinds of nucleic acids such as RNAs and DNAs. Studies have found that EVs contain double-stranded DNA and that genetic information has a certain degree of consistency with tumor DNA. Therefore, if genes that exist in exosomes are stable, we may be able to use EVs genetic testing as a new means to monitor gene mutation. METHODS: In this study, EVs were extracted from serum under various storage conditions (4 degrees C, room temperature and repeated freeze-thaw). We used western blotting to examine the stability of serum EVs. Then, we extracted DNA from EVs and tested the concentration changing under different conditions. We further assessed the stability of EVs DNA s using polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: EVs is stable under the conditions of 4 degrees C (for 24 h, 72 h, 168 h), room temperature (for 6 h, 12 h, 24 h, 48 h) and repeated freeze-thaw (after one time, three times, five times). Also, serum DNA is mainly present in EVs, especially in exosomes, and that the content and function of DNA in EVs is stable whether in a changing environment or not. We showed that EVs DNA stayed stable for 1 week at 4 degrees C, 1 day at room temperature and after repeated freeze-thaw cycles (less than three times). However, DNA from serum EVs after 2 days at room temperature or after five repeated freeze-thaw cycles could be used for PCR and sequencing. CONCLUSIONS: Serum EVs and EVs DNA can remain stable under different environments, which is the premise that EVs could serve as a novel means for genetic tumor detection and potential biomarkers for cancer diagnostics and prognostics. PMID- 27662834 TI - Age at menarche in Korean adolescents: trends and influencing factors. AB - BACKGROUND: An increased incidence of central precocious puberty has been recently reported in South Korea, which suggests an ongoing downward trend in pubertal development in the Korean population. We aimed to verify the trend in age at menarche in young Korean women during the last decade and associated factors. METHODS: We analyzed a population-based sample of 3409 Korean girls, aged 10-18 years, using data from the Korean National Health and Nutrition Examination Surveys (KNHANES) II (2001), III (2005), IV (2007-2009), and V (2010 and 2011). Average age at menarche was studied using the Kaplan-Meier survival method and predictors were analyzed using Cox proportional hazards model. The percentage of subjects who had experienced menarche at each age level was compared by using the Cochran-Armitage test. RESULTS: Overall mean age at menarche was 12.7 years. The percentage of subjects who experienced menarche before the age of 12 years was 21.4 % in 2001 but increased to 34.6 % in 2010/2011 (p < 0.01). In addition, the percentage of girls who experienced menarche before the age of 14 years increased from 76 % in 2001 to 92 % in 2010/2011 (p < 0.005). Adolescents whose mothers who had experienced early menarche (HR 1.48, 95 % CI [1.22-1.80]), and adolescents who were overweight (HR 1.24, 95 % CI [1.04-1.49]) were more likely to have experienced menarche. Additionally, underweight adolescents (HR 0.27, 95 % CI [0.12-0.60]) and adolescents who had a mother having late menarche (HR 0.68, 95 % CI [0.59-0.79]) were expected to have late menarche. None of the socioeconomic factors assessed in our study showed an association with age at menarche. CONCLUSIONS: A downward trend in age at menarche was defined in Korean adolescents during the last decade. Furthermore, influences of genetic and nutritional parameters on individual variance in age at menarche were defined. PMID- 27662835 TI - The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes. AB - KEY MESSAGE: This study highlights the changes in umami-related nucleotide and glutamate levels when the AMP deaminase gene was elevated in transgenic tomato. Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour can be imparted by the presence of glutamate and is greatly enhanced by the addition of ribonucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP). The production of IMP is regulated by the enzyme adenosine monophosphate (AMP) deaminase which functions to convert AMP into IMP. We have generated transgenic tomato (Solanum lycopersicum) lines over expressing AMP deaminase under the control of a fruit-specific promoter. The transgenic lines showed substantially enhanced levels of AMP deaminase expression in comparison to the wild-type control. Elevated AMP deaminase levels resulted in the reduced accumulation of glutamate and increased levels of the umami nucleotide GMP. AMP concentrations were unchanged. The effects on the levels of glutamate and GMP were unexpected and are discussed in relation to the metabolite flux within this pathway. PMID- 27662836 TI - Biodegradation of nonionic and anionic surfactants in domestic wastewater under simulated sewer conditions. AB - The ultimate disposition of chemicals discarded down the drain can be substantially impacted by their fate in the sewer, but to date limited data have been published on the biodegradability of chemicals in sewer systems. The recently established OECD 314 guideline (Simulation tests to assess the biodegradability of chemicals discharged in wastewater, 2008) contains a simulation method (314A) for evaluating the biodegradation of chemicals in sewage under simulated sewer conditions. This research used the OECD 314A method to evaluate the rates and pathways of primary and ultimate biodegradation of a suite of 14C-labeled homologues representing four classes of high volume surfactants including nonionic alkyl ethoxylates (AE), and anionic alkyl ethoxysulfates (AES), alkyl sulfate (AS) and linear alkyl benzene sulfonate (LAS). All the tested homologues exhibited >97 % loss of parent, formation of metabolites, and some level (16-94 %) of CO2 production after being incubated 96-100 h in raw domestic wastewater. Comparison of C12E3, C14E3, and C16E3 showed that the first order biodegradation rate was affected by alkyl chain length with rates ranging from 6.8 h-1 for C12E3 to 0.49 h-1 for C16E3. Conversely, comparison of C14E1, C14E3, and C14E9 showed that the number of ethoxy units did not impact the biodegradation rate. AES and AS degraded quickly with first order kinetic rates of 1.9-3.7 and 41 h-1 respectively. LAS did not exhibit first order decay kinetics and primary degradation was slow. Biodegradation pathways were also determined. This work shows that biodegradation in the sewer has a substantial impact on levels of surfactants and surfactant metabolites that ultimately reach wastewater treatment plants. PMID- 27662837 TI - Social Anxiety Symptoms in Young Children: Investigating the Interplay of Theory of Mind and Expressions of Shyness. AB - Children's early onset of social anxiety may be associated with their social understanding, and their ability to express emotions adaptively. We examined whether social anxiety in 48-month-old children (N = 110; 54 boys) was related to: a) a lower level of theory of mind (ToM); b) a lower proclivity to express shyness in a positive way (adaptive); and c) a higher tendency to express shyness in a negative way (non-adaptive). In addition, we investigated to what extent children's level of social anxiety was predicted by the interaction between ToM and expressions of shyness. Children's positive and negative expressions of shyness were observed during a performance task. ToM was measured with a validated battery, and social anxiety was assessed using both parents' reports on questionnaires. Socially anxious children had a lower level of ToM, and displayed more negative and less positive shy expressions. However, children with a lower level of ToM who expressed more positive shyness were less socially anxious. Additional results show that children who displayed shyness only in a negative manner were more socially anxious than children who expressed shyness only in a positive way and children who did not display any shyness. Moreover, children who displayed both positive and negative expressions of shyness were more socially anxious than children who displayed shyness only in a positive way. These findings highlight the importance of ToM development and socio-emotional strategies, and their interaction, on the early development of social anxiety. PMID- 27662838 TI - Microbial HSP70 peptide epitope 407-426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer. AB - Tumor-derived autophagome (DRibble) is an effective therapeutic cancer vaccine inducing T cell recognition and death of tumor cells in mice. However, the potential for improved anti-tumor response still remains. Our previous study demonstrated that two repeats of a mycobacterial HSP70407-426 (M2) peptide acted as adjuvant in improving anti-tumor efficacy of human umbilical vein endothelial cell (HUVEC) vaccine. Here, a DRibble vaccine conjugated with M2 (DRibble-M2) was designed as a novel vaccine to enhance anti-tumor activity. Compared with DRibble alone, DRibble-M2 vaccination more significantly inhibited the growth of mouse Lewis lung cancer both in a subcutaneous tumor model and in a lung metastasis model. Higher expression of antigen-specific CTL was induced by DRibble-M2. DRibble-M2 induced higher CD83 and CD86 expression in DC2.4 and also improved the internalization of DRibble antigen into DC2.4. Our data indicated that DRibble-M2 is a potential vaccine for clinical cancer therapy. PMID- 27662839 TI - Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance. AB - Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments. GANT61 very efficiently inhibited cell colony growth in glioma cell lines, compared to temozolomide. Moreover, a synergic effect of GANT61 and temozolomide drastically decreased the LD50 of temozolomide in the cell colony experiments. Therefore, our results suggest that there is a potential nexus of Shh-Gli1-BMI1 cell signaling to regulate MRP1 and to promote chemoresistance in glioma. Henceforth, our study opens the possibility of facing new targets, Gli1 and BMI1, for the effective treatment of glioma suppression of chemoresistance with adjuvant therapy of GANT61 and temozolomide. PMID- 27662840 TI - NTRK2 is an oncogene and associated with microRNA-22 regulation in human gastric cancer cell lines. AB - In this study, we examined the roles of neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene in regulating in vitro proliferation and invasion in human gastric cancer. Gene expression of NTRK2 was compared between non-carcinoma gastric epithelial cells and gastric cancer (GC) cells by quantitative RT-PCR (qRT-PCR). NTRK2 was either downregulated or upregulated in MKN-28 and SNU-719 cells. The effect of NTRK2 downregulation or upregulation on GC in vitro development was analyzed by qRT-PCR, western blot, proliferation assay, and invasion assay, respectively. The upstream regulator of NTRK2, microRNA-22 (miR 22), was evaluated by dual-luciferase assay. MiR-22 was then upregulated in MKN 28 and SNU-719 cells to examine its regulation on NTRK2 and its encoded protein, tyrosine kinase receptor B (TrkB). In miR-22-upregulated MKN-28 and SNU-719 cells, NTRK2 was further overexpressed to evaluate functional interaction between miR-22 and NTRK2 in GC. NTRK2 was aberrantly upregulated in GC cell lines than in normal gastric cells. In MKN-28 and SNU-719 cells, NTRK2 downregulation inhibited whereas NTRK2 upregulation promoted GC proliferation and invasion in vitro. MiR 22 was verified to be an inverse upstream regulator of NTRK2. In miR-22 upregulated MKN-28 and SNU-719 cells, NTRK2 overexpression partially reversed the miR-22-induced inhibition on cancer proliferation and invasion. NTRK2 is an oncogene and reversely associated with miR-22 in regulating in vitro cancer development in GC. PMID- 27662841 TI - Insulin-like growth factor-related components and the risk of liver cancer in a nested case-control study. AB - Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 - IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026 0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 - IGF1) may be inversely associated with the incidence of hepatoma. PMID- 27662842 TI - Identification of control targets in Boolean molecular network models via computational algebra. AB - BACKGROUND: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. RESULTS: This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg . CONCLUSIONS: This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks. PMID- 27662843 TI - QTL mapping of Fusarium head blight resistance in three related durum wheat populations. AB - KEY MESSAGE: The QTL Fhb1 was successfully introgressed and validated in three durum wheat populations. The novel germplasm and the QTL detected will support improvement of Fusarium resistance in durum wheat. Durum wheat (Triticum durum Desf.) is particularly susceptible to Fusarium head blight (FHB) and breeding for resistance is hampered by limited genetic variation within this species. To date, resistant sources are mainly available in a few wild relative tetraploid wheat accessions. In this study, the effect of the well-known hexaploid wheat (Triticum aestivum L.) quantitative trait locus (QTL) Fhb1 was assessed for the first time in durum wheat. Three F7-RIL mapping populations of about 100 lines were developed from crosses between the durum wheat experimental line DBC-480, which carries an Fhb1 introgression from Sumai-3, and the European T. durum cultivars Karur, Durobonus and SZD1029K. The RILs were evaluated in field experiments for FHB resistance in three seasons using spray inoculation and genotyped with SSR as well as genotyping-by-sequencing markers. QTL associated with FHB resistance were identified on chromosome arms 2BL, 3BS, 4AL, 4BS, 5AL and 6AS at which the resistant parent DBC-480 contributed the positive alleles. The QTL on 3BS was detected in all three populations centered at the Fhb1 interval. The Rht-B1 locus governing plant height was found to have a strong effect in modulating FHB severity in all populations. The negative effect of the semi-dwarf allele Rht-B1b on FHB resistance was compensated by combining with Fhb1 and additional resistance QTL. The successful deployment of Fhb1 in T. durum was further substantiated by assessing type 2 resistance in one population. The efficient introgression of Fhb1 represents a significant step forward for enhancing FHB resistance in durum wheat. PMID- 27662844 TI - Identification of loci controlling forage yield and nutritive value in diploid alfalfa using GBS-GWAS. AB - KEY MESSAGE: We attempted to identify genomic regions controlling forage yield and nutritive value in alfalfa. Several candidate genes and associated genetic markers were identified that could potentially be useful for alfalfa breeding to more efficiently develop improved cultivars. Alfalfa is one of the most widely cultivated forage legumes worldwide and improving alfalfa forage yield and nutritive value is a major global breeding goal. Genotyping-by-sequencing (GBS) provides cost-effective molecular marker genotyping for genome-wide association studies (GWAS). Using more than 15,000 genome-wide single nucleotide polymorphisms (SNP) identified from GBS, we conducted a GWAS to investigate forage yield and nutritive value-related traits. We have detected a number of associations for all the traits evaluated and a number of associations detected were located on the Medicago truncatula genome. The SNP in a coding region of a cell wall biosynthesis gene was associated with several cell wall-related traits, and we suggest that it may be the causative polymorphism. Two other SNPs residing in meristematic development and early growth genes were found to associate with the total biomass yield. None of the SNPs associated with regrowth after harvest or with spring regrowth were mapped to the M. truncatula genome, possibly reflecting the fact that M. truncatula is an annual species related to alfalfa that typically has limited ability to regrow. The alleles we identify with the major impact on forage yield and nutritive value can be rapidly incorporated into our breeding program. PMID- 27662845 TI - Body mass index and incidence of thyroid cancer in Korea: the Korean Cancer Prevention Study-II. AB - PURPOSE: The prevalence of thyroid cancer and obesity has increased worldwide. However, their association has remained controversial and few studies have been performed in Asia. Our study evaluated the correlation between the incidence of thyroid cancer and body mass index (BMI) in Korea. METHODS: This is a multi centered, prospective cohort study from the Korean Cancer Prevention Study-II. A total of 141,157 individuals between 1994 and 2012, including 1546 newly developed thyroid cancer patients, were enrolled. Subjects were divided into four groups on the BMI. Person-years, incidence rate, and hazard ratios (HRs) were calculated using the Cox proportional hazard model. RESULTS: The increasing trends of HRs of thyroid cancer in men and women younger than 50 years of age were observed as BMI increased (P trend <0.001 in both groups). However, in women older than 50 years of age, there was no association between thyroid cancer incidence and BMI. CONCLUSIONS: Our findings suggest that positive association between thyroid cancer incidence and high BMI in men and women under 50 years old. Based on these results, we suggest that obese men and women under 50 years old are better to be considered for the higher possibility of thyroid cancer development, and more efforts are needed to control weight gain. PMID- 27662846 TI - Association between GDF5 +104T/C polymorphism and knee osteoarthritis in Caucasian and Asian populations: a meta-analysis based on case-control studies. AB - BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease with a complex genetic background. Variants in growth differentiation factor 5 (GDF5) have been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The present study aimed to assess the association between the GDF5 +104T/C polymorphism and the susceptibility of the knee to OA through a meta analysis of available case-control studies. METHODS: The PubMed and Science Direct citation databases were used to search electronic literature in order to identify studies published between January 2007 and July 2016 that evaluated the association between the GDF5 +104T/C polymorphism and the susceptibility of the knee to OA. Different genetic models were used to assess the pooled and stratified data. RESULTS: A positive association was found in all pooled studies (OR = 0.808, 95 % CI = 0.754-0.866, p < 0.001). Regarding genotypes, significant associations were found using a dominant model (OR = 0.777, 95 % CI = 0.708 0.852, p < 0.001), a recessive model (OR = 0.723, 95%CI = 0.623-0.839, p < 0.001), and an additive model (CC vs TT OR = 0.648, 95 % CI = 0.552-0.760, p < 0.001; CC vs CT OR = 0.801, 95 % CI = 0.685-0.936, p = 0.005). Meta-analysis data were stratified by ethnicity, and the GDF5 C allele was found to be positively associated with OA of the knee in both Caucasians and Asians, as were the GDF5 TC and CC genotypes. In addition, using an additive model, the CC genotype was found to be significantly associated with OA of the knee in both Caucasians and Asians when comparing CC vs TT genotypes, but not in Caucasians when comparing TT vs CT genotypes. CONCLUSIONS: Meta-analysis results indicated that the GDF5 +104T/C polymorphism is a protective factor for OA among Caucasian and Asian populations. PMID- 27662847 TI - Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency. AB - BACKGROUND: Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. METHODS AND RESULTS: Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3-93.1 mL/m2; P=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m2 at 8 months, P=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. CONCLUSIONS: hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies. PMID- 27662849 TI - Saturation Binding of Nicotine to Synthetic Neuromelanin Demonstrated by Fluorescence Spectroscopy. AB - Neuromelanin (NM) has long been considered as an aging pigment, perhaps an unavoidable and undesirable byproduct of dopaminergic neural transmission. However, NM is carefully packaged into double membrane-bound structures within cells of the substantia nigra and other neural tissues, suggesting a beneficial function to maintaining these stores. It is well established that NM is able to concentrate toxic xenobiotics within pigmented cells due to its unique chemical environment. In doing so, such agents may confer susceptibility to Parkinson's disease (PD) as illustrated by model PD-inducing neurotoxins such as methyl phenyl-pyridinium ion. It is possible that high-affinity binding interactions toward NM may contribute to the adverse effects of PD-inducing toxins, as well as neuroprotective agents. Here we aim to develop a generalized assay capable of elucidating the binding constants of chemical agents to synthetic and natural neuromelanins. Toward this end, a model neuromelanin synthesized from dopamine and cysteine was prepared according to published procedure. Using a UV/Visible spectroscopic assay, we show that dopamine, 6-hydroxy dopamine, and nicotine bind to the synthetic neuromelanin, while caffeine did not. More importantly, nicotine was further found to induce a fluorescence signal in the presence of NM which was used to establish a binding constant estimated at 0.65 mM. Dopamine appears to enhance this signal, also in a saturable manner, with an estimated Kd of 0.05 mM in our isolated chemical system. In summary, the micro-scale fluorescence assay described herein will allow us to overcome many of the problems inherent in the study of chemical interaction with NM through traditional spectroscopic means. Using a single standardized signal, it should now be possible to rank a number of PD-related toxins based on NM-binding affinity and shed further light on this important problem. PMID- 27662848 TI - Segond fracture: an MR evaluation of 146 patients with emphasis on the avulsed bone fragment and what attaches to it. AB - OBJECTIVE: To re-evaluate the Segond fragment emphasizing those structures that attach to the fragment in patients with reported acute/subacute anterior cruciate ligament (ACL) injuries, and to clarify the nomenclature used to describe these structures. MATERIALS AND METHODS: A search of databases of knee MR examinations over 4.5 years with reported ACL tears yielded 19,726 studies. Using strict exclusion criteria, a total of 146 MR studies with acute/subacute ACL tears were re-assessed with respect to the Segond fragment's size, shape, orientation, location, displacement, attaching soft tissue structures, and associated osseous and/or soft tissue injuries. RESULTS: Segond fractures were present in 1.25 % of reported acute/subacute ACL tears. The fragment measured 11.9 * 7.3 * 3.27 mm, being thin, ovoid, vertically oriented, situated anterolaterally along the proximal tibial epiphysis, posterior to Gerdy's tubercle and inferior to the lateral tibial plateau, and displaced up to 6 mm laterally. The attached structures were the meniscotibial component of the mid-third lateral capsular ligament (mt-MTLCL) in 58.9 %, both the mt-MTLCL and the posterior fibers of the ITB (pf-ITB) in 35.6 %, and the pf-ITB in 5.48 % of cases. In no case was there an additional attaching structure that did not meet criteria for the mt-MTLCL or the pf-ITB. CONCLUSION: The mt-MTLCL most commonly attaches to the Segond fragment, but the pf-ITB can also attach to this fragment. In no case was there an additional attaching structure that did not meet criteria for the mt-MTLCL or the pf-ITB. PMID- 27662851 TI - Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion. AB - We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot. Pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and anti-inflammatory cytokine interleukin-10 (IL-10) levels were determined by ELISA. Compared with the control groups on week 2, 4 and 6, in CCPA-treated groups, the ratio of P-mTOR/mTOR, expression of MBP and IL-10 increased markedly, while the expression of TNF-alpha reduced at week 6. In conclusion, A1ARs appears to reduce inflammation in white matter via the mTOR signaling pathway in the rUCCAO mice. Therefore, A1ARs may serve as a therapeutic target during the repair of white matter lesions under CCH. PMID- 27662850 TI - MEKK1 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage. AB - The JNKs have been implicated in a variety of biological functions in mammalian cells, including apoptosis and the responses to stress. However, the physiological role of these pathways in the intracerebral hemorrhage (ICH) has not been fully elucidated. In this study, we identified a MAPK kinase kinase (MAPKKK), MEKK1, may be involved in neuronal apoptosis in the processes of ICH through the activation of JNKs. From the results of western blot, immunohistochemistry and immunofluorescence, we obtained a significant up regulation of MEKK1 in neurons adjacent to the hematoma following ICH. Increasing MEKK1 level was found to be accompanied with the up-regulation of p-JNK 3, p53, and c-jun. Besides, MEKK1 co-localized well with p-JNK in neurons, indicating its potential role in neuronal apoptosis. What's more, our in vitro study, using MEKK1 siRNA interference in PC12 cells, further confirmed that MEKK1 might exert its pro-apoptotic function on neuronal apoptosis through extrinsic pathway. Thus, MEKK1 may play a role in promoting the brain damage following ICH. PMID- 27662852 TI - Characteristics of uranium biosorption from aqueous solutions on fungus Pleurotus ostreatus. AB - Uranium(VI) biosorption from aqueous solutions was investigated in batch studies by using fungus Pleurotus ostreatus biomass. The optimal biosorption conditions were examined by investigating the reaction time, biomass dosage, pH, temperature, and uranium initial concentration. The interaction between fungus biomass and uranium was confirmed using Fourier transformed infrared (FT-IR), scanning electronic microscopy energy dispersive X-ray (SEM-EDX), and X-ray photoelectron spectroscopy (XPS) analysis. Results exhibited that the maximum biosorption capacity of uranium on P. ostreatus was 19.95 +/- 1.17 mg/g at pH 4.0. Carboxylic, amine, as well as hydroxyl groups were involved in uranium biosorption according to FT-IR analysis. The pseudo-second-order model properly evaluated the U(VI) biosorption on fungus P. ostreatus biomass. The Langmuir equation provided better fitting in comparison with Freundlich isotherm models. The obtained thermodynamic parameters suggested that biosorption is feasible, endothermic, and spontaneous. SEM-EDX and XPS were additionally conducted to comprehend the biosorption process that could be described as a complex process involving several mechanisms of physical adsorption, chemisorptions, and ion exchange. Results obtained from this work indicated that fungus P. ostreatus biomass can be used as potential biosorbent to eliminate uranium or other radionuclides from aqueous solutions. PMID- 27662853 TI - Microbial structure and nitrogen compound conversions in aerobic granular sludge reactors with non-aeration phases and acetate pulse feeding. AB - A technological system was developed for efficient nitrogen removal from real digester supernatant in a single reactor with shortened aeration to increase the economical aspects of wastewater treatment. The supernatant (600 mg TKN/L, low COD/N ratio of 2.2) was treated in batch reactors with aerobic granules (GSBRs) to test how one, two, or three non-aeration phases and acetate pulse feeding in the cycle affect the morphological and microbial properties of biomass. Introduction of one non-aeration phase in the cycle increased nitrogen removal efficiency by 11 % in comparison with constantly aerated GSBR. The additional non aeration phases did not diminish the efficiency of ammonia oxidation but did favor nitrification to nitrate. Acetate pulse feeding in the reactor with three non-aeration phases raised the efficiency of nitrogen removal to 77 %; in parallel, the number of denitrifiers possessing nosZ genes and performing denitrification to N2 increased. Ammonia was oxidized by aerobic and anaerobic ammonia-oxidizing bacteria and heterotrophic nitrifiers (Pseudomonas sp. and Alcaligenes faecalis) that coexisted in granules. Azoarcus sp., Rhizobium sp., and Thauera sp. were core genera of denitrifiers in granules. An increase in the number of non-aeration phases diminished EPS content in the biomass and granule diameters and increased granule density. PMID- 27662854 TI - Elemental sulfur in sediments: analytical problems. AB - In the paper, a modified method for elemental sulfur (S8) determining using gas chromatography coupled with mass spectrometry (GC-MS) is proposed with estimation of selected validation parameters. The aim of this work was a review of problems associated with the determination of S8 and selection of the most optimal conditions for S8 analysis with GC-MS. The presented studies have shown that the temperature of the injector and the chromatographic column during S8 determination should not exceed 180 degrees C. At temperatures over 180 degrees C, the sulfur S8 is decomposed to the other sulfur species such as S2, S3, S4, S5, and S6. During decreasing injector and column temperature below 180 degrees C the chromatographic peak eluted as S8 is badly extended and asymmetric. To minimize the problems of S8 decomposition to other sulfur species during chromatographic process also other parameters of the GC-MS have been selected. In order to apply the proposed method for real sediments samples, determination of sulfur S8 in bottom sediments, collected in the Gulf of Gdansk (southern Baltic Sea), has been performed. The concentration of S8 fell in the range from below the limit of detection to 0.1432 +/- 0.0095 mg/g d.w. The research has also shown that addition of approx. 200 mg of activated copper is effective for removing sulfur from bottom sediment extracts. PMID- 27662855 TI - Sol-gel synthesis of TiO2 nanoparticles: effect of Pluronic P123 on particle's morphology and photocatalytic degradation of paraquat. AB - We report a facile method to tune TiO2 nanoparticles' morphology by modifying and an acid-catalyzed sol-gel synthesis with Pluronic P123. Synthesized particles were characterized by transmission electron microscopy, BET analysis, and X-ray diffraction spectroscopy. XRD analysis revealed a high anatase content while BET measurements showed that porous volume strongly depends on the amount of P123. We demonstrate that high amounts of P123 increase particle's aspect-ratio from spherical to rod-shape morphology. We evaluated the photocatalytic performances for the removal of methyl viologen (paraquat) and found that best performances are obtained for the following weight ratio P123/TiO2 = 7.5. Furthermore, P25 is less active than synthesized nanoparticles. PMID- 27662856 TI - Tetracycline uptake and metabolism by vetiver grass (Chrysopogon zizanioides L. Nash). AB - Environmental contamination by antibiotics not only perturbs the ecological balance but also poses a risk to human health by promoting the development of multiantibiotic-resistant bacteria. This study focuses on identifying the biochemical pathways associated with tetracycline (TC) transformation/degradation in vetiver grass that has the potential to be used as a biological remediation system in TC-contaminated water sources. A hydroponic experimental setup was used with four initial TC concentrations (0, 5, 35, 75 ppm), and TC uptake was monitored over a 30-day period. Results show that TC transformation in the media occurred during the first 5 days, where a decrease in the parent compound and an increase in the concentration of the isomers such as epitetracycline (ETC) and anhyrotetracycline (ATC) occurred, and TC disappeared in 20 days in tanks with vetiver grass. However, the isomers ETC and ATC remained in the control tanks for the duration of the trial. Transformation products of TC in plant tissue were analyzed by using ultra HPLC high-resolution Orbitrap mass spectrometery (HRMS/MS), which indicates amide hydrolysis of TC in vetiver roots. Metabolic profiling revealed that glyoxylate metabolism, TCA cycle, biosynthesis of secondary metabolites, tryptophan metabolism, and inositol phosphate metabolism were impacted in vetiver root by TC treatment. PMID- 27662858 TI - Bioactive and functional properties of protein hydrolysates from fish frame processing waste using plant proteases. AB - Enzymatic conversion of fish frame waste of threadfin breams (Nemipterus japonicus) to protein hydrolysate could be a solution for minimizing the pollution issues related to seafood processing operations and a way for the value addition to processing by-products. Protein hydrolysates from fish frame waste (FW) of thread fin breams (N. japonicus) were prepared and evaluated for bioactive properties such as angiotensin-I-converting enzyme (ACE) inhibitory activity and antioxidant and functional properties as a function of degree of hydrolysis (DH). Two different plant proteases, papain and bromelain, were used to prepare fish protein hydrolysates (FPH) and designated as HP (hydrolysates prepared using papain) and HB (hydrolysates prepared using bromelain). The ACE inhibitory activity of HP samples was higher at 5 and 10 % DH than that of the HB samples at DH 15 %, and there was no significant difference (p < 0.05). Antioxidant properties (2, 2 diphenyl-1-picrylhydrazyl [DPPH] radical scavenging activity, ferric reducing power and lipid peroxidation inhibition) of hydrolysates increased with increase in DH. The HB samples at DH 15 % had significantly higher antioxidant properties than HP samples (p < 0.05). The solubility of HP and HB samples was high in a wide range of pH and increased with DH. The functional properties of HP and HB samples decreased significantly with increase in DH (p < 0.05). The fractionation of the HB-DH 15 % sample yielded three peptide fractions with the approximate molecular weight of peptides in the range of 7562-812 Da. Relatively, bromelain enzyme is more effective in producing the FPH with desirable bioactive and functional properties. PMID- 27662857 TI - Assessment of toxic and endocrine potential of substances migrating from selected toys and baby products. AB - Analysis of literature data shows that there is limited information about the harmful biological effects of mixture of compounds from the EDC group that are released from the surface of toys and objects intended for children and infants. One of the tools that can be used to obtain such information is appropriate bioanalytical tests. The aim of this research involved determining whether tests that use living organisms as an active element (Vibrio fischeri-Microtox(r), Heterocypris incongruens-Ostrocodtoxkit FTM and the XenoScreen YES/YASTM test of oestrogenic/androgenic activity) can be a tool for estimating the combined toxic effects induced by xenobiotics released from objects intended for children. To reproduce the conditions to which objects are exposed during their use, liquids with a composition corresponding to that of human bodily fluids (artificial sweat and saliva) were used. This research focused on the main parameters influencing the intensification of the migration process (temperature, contact time and composition of the extraction mixture). The studies aimed to estimate the endocrine potential of the extracts showed that compounds released from the surface of studied objects exhibit antagonistic androgenic activity. While on the basis of the results of Microtox(r) test, one can state that the largest quantity of toxic compounds are released in the first 2 h of using the object. The FTIR spectra analyses confirmed that no degradation of polymeric material took place. On the basis of the results obtained, it was unanimously concluded that contact of the object with bodily fluids may result in the release of a large number of xenobiotics, which has disadvantageous effects on the metabolic processes of the indicator organisms. PMID- 27662860 TI - A review of the Texas, USA San Jacinto Superfund site and the deposition of polychlorinated dibenzo-p-dioxins and dibenzofurans in the San Jacinto River and Houston Ship Channel. AB - The San Jacinto River (SJR) waste pits that lie just under the 1-10 overpass in eastern Harris County east of Houston, Texas, USA, were created in the 1960s as dumping grounds for paper mill waste. The deposition of this waste led to accumulation of highly toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCCDDs/PCDFs) over the course of several decades. After abandonment, the waste material eventually became submerged under the waters of the SJR, resulting in widespread environmental contamination that currently constitutes a significant health concern for eastern Harris County communities. The original waste pits were rediscovered in 2005, and the San Jacinto waste site is now a designated EPA superfund site. The objective of this review then is to discuss the history and current state of containment around the San Jacinto waste pits and analyze spatial and temporal trends in the PCDD/PCDF deposition through the SJR system from the data available. We will discuss the current exposure and health risks represented by the Superfund site and the SJR system itself, as well as the discovery of liver, kidney, brain (glioma), and retinoblastoma cancer clusters in eastern Harris County across multiple census tracts that border the Superfund site. We will also cover the two primary management options, containment versus removal of the waste from the Superfund and provide recommendations for increased monitoring of existing concentrations of polychlorinated waste in the SJR and its nearby associated communities. PMID- 27662859 TI - Risk assessment and vertical distribution of thallium in paddy soils and uptake in rice plants irrigated with acid mine drainage. AB - The objective of this paper is to assess the influence of irritating paddy fields with acid mine drainage containing thallium (Tl) to rice plant-soil system and potential health risks for local residents. Vertical distribution of Tl, pH, organic matter (OM), and cation exchange capacity (CEC) in 24 paddy soil profiles around Yunfu pyrite mine area was investigated. Rice plant samples were collected from the corresponding soil sampling site. The results showed that Tl concentrations in paddy soils at 0-60 cm depth range from 3.07 to 9.42 mg kg-1, with a mean of 5.74 mg kg-1, which were significantly higher than the background value of soil in China (0.58 mg kg-1). On the whole, Tl contents in paddy soil profiles increased quickly with soil depth from 0 to 30 cm and decreased slowly with soil depth from 30 to 60 cm. The soil Tl content was significant negatively correlated with soil pH. The mean content of Tl in the root, stem, leaf, and rice was 4.36, 1.83, 2.74, and 1.42 mg kg-1, respectively, which exceeded the proposed permissible limits for foods and feedstuffs in Germany. The Tl content in various tissues of the rice plants followed the order root > leaf > stem (rice), which suggested that most Tl taken up by rice plants retained in the root, and a little migrated to the leaf, stem, and rice. Correlation analysis showed that Tl content in root was significant positively correlated with Tl content in leaf and rice. The ranges of hazard quotient (HQ) values were 4.08~24.50 and 3.84~22.38 for males and females, respectively. Males have higher health risk than females in the same age group. In childhood age groups (2 to <21 years) and adult age groups (21 to <70 years), the highest health risk level was observed in the 11 to 16 age group and 21 to 50 age group, respectively. The findings indicated that regular irrigation with Tl-bearing acid mine drainage led to considerable contamination of Tl in paddy soil and rice plant. Local government should take various measures to treat Tl contamination, especially the tailings. PMID- 27662862 TI - Antioxidative response of olive to air emissions from tire burning under various zinc nutritional treatments. AB - Uniform 2-year old seedlings of a commercial olive cultivar (Olea europaea L., cv. Mahzam) were exposed or unexposed to the air pollution from the controlled burning of waste tires. The plants were supplied with zinc sulfate (ZnSO4) or synthesized Zn(Glycine)2 (Zn-Gly) or unsupplied with Zn. Exposure to air pollution resulted in oxidative damage to the olive, as indicated by the higher production of malondialdehyde (MDA). Supplement with Zn partly alleviated oxidative damage induced by the air emissions on the olive. Leaf concentration of MDA was higher at the active period of tire burning than that of the inactive one. Exposure to the emissions from tire burning significantly increased leaf ascorbate peroxidase (APX) activity. Supplement with Zn increased APX activity in plants exposed to the air pollution. According to the results, Zn nutrition was effective in alleviating oxidative stress induced by air pollution on the olive. APX seemed to play a significant role in alleviating oxidative damages induced by air emissions from tire burning on the olive; however, the role of other antioxidant enzymes should be addressed in future studies. PMID- 27662861 TI - Vetiver plantlets in aerated system degrade phenol in illegally dumped industrial wastewater by phytochemical and rhizomicrobial degradation. AB - This research evaluated the feasibility of using vetiver plantlets (Vetiveria zizanioides (L.) Nash) on a floating platform with aeration to degrade phenol (500 mg/L) in illegally dumped industrial wastewater (IDIWW). The IDIWW sample was from the most infamous illegal dumping site at Nong Nae subdistrict, Phanom Sarakham district, Chachoengsao province, Thailand. Laboratory results suggested that phenol degradation by vetiver involves two phases: Phase I, phytopolymerization and phyto-oxidation assisted by root-produced peroxide (H2O2) and peroxidase (POD), followed by phase II, a combination of phase I with enhanced rhizomicrobial degradation. The first 360-400 h of phenol degradation were dominated by phytopolymerization and phyto-oxidation yielding particulate polyphenols (PPP) or particulate organic matter (POM) as by-products, while phenol decreased to around 145 mg/L. In Phase II, synergistically, rhizomicrobial growth was ~100-folds greater on the roots of the vetiver plantlets than in the IDIWW and participated in the microbial degradation of phenol at this lower phenol concentration, increasing the phenol degradation rate by more than three folds. This combination of phytochemical and rhizomicrobiological processes eliminated phenol in IDIWW in less than 766 h (32 days), while without the vetiver plantlets, phenol degradation by aerated microbial degradation alone may require 235 days. To our knowledge, this is the first that systematically reveals the complete phenol degradation mechanism by vetiver plantlets in real aerated wastewater. PMID- 27662863 TI - An assessment of the effect of contact time on cadmium phytoavailability in a pasture soil. AB - The length of time cadmium (Cd) is in contact with the soil has been recognised as a factor affecting phytoavailability, but the extent of this process is currently poorly understood. This study used isotopic dilution techniques (E and L values) to determine the effect of contact time on Cd phytoavailability from soil collected from a long-term phosphorus (P) fertiliser trial. Cadmium phytoavailability was determined in soil that was last fertilised with soluble Cd from P fertiliser 17 years prior to sampling (residual plots) and soil that received annual applications of P fertiliser until sampling (continuous plots). It was found that both E values and L values increased with P fertiliser (viz Cd) inputs and were significantly related to each other (r 2 = 0.82 P < 0.005). There was however no significant difference (P < 0.05) in the percentage of total Cd that was phytoavailable calculated using E values (E%) between the continuous (mean 51 %) and the residual plots (mean 51 %). There was also no significant difference (P < 0.05) in the percentage of total soil Cd that was phytoavailable calculated using L values (L%) between the continuous (mean 77 %) and residual plots (mean 87 %). These results suggest that despite Cd being in contact with the soil for 17 years, there was no difference in the size of the phytoavailable Cd pool compared to recent Cd inputs. This study should be repeated for other soil types and factored into any analysis for the long-term implications of ongoing Cd accumulation in soil on future landuse. PMID- 27662864 TI - Erythema gyratum repens: a pathogenetic mystery and therapeutic challenge. PMID- 27662865 TI - Cellular Fractionation and Isolation of Chromatin-Associated RNA. AB - In eukaryotic cells, the synthesis, processing, and functions of RNA molecules are confined to distinct subcellular compartments. Biochemical fractionation of cells prior to RNA isolation thus enables the analysis of distinct steps in the lifetime of individual RNA molecules that would be masked in bulk RNA preparations from whole cells. Here, we describe a simple two-step differential centrifugation protocol for the isolation of cytoplasmic, nucleoplasmic, and chromatin-associated RNA that can be used in downstream applications such as qPCR or deep sequencing. We discuss various aspects of this fractionation protocol, which can be readily applied to many mammalian cell types. For the study of long noncoding RNAs and enhancer RNAs in regulation of transcription especially the preparation of chromatin-associated RNA can contribute significantly to further developments. PMID- 27662866 TI - Knockdown of Nuclear-Located Enhancer RNAs and Long ncRNAs Using Locked Nucleic Acid GapmeRs. AB - The human genome is widely transcribed outside of protein-coding genes, producing thousands of noncoding RNAs from different subfamilies including enhancer RNAs. Functional studies to determine the role of individual genes are challenging with noncoding RNAs appearing to be more difficult to knockdown than mRNAs. One factor that may have hindered progress is that the majority of noncoding RNAs are thought to be located within the nucleus, where the efficiency of traditional RNA interference techniques is debatable. Here we present an alternative RNA interference technique utilizing Locked Nucleic Acids, which is able to efficiently knockdown noncoding RNAs irrespective of intracellular location. PMID- 27662867 TI - Visualization of Enhancer-Derived Noncoding RNA. AB - Enhancers are principal regulators that allow spatiotemporal tissue-specific control of gene expression. While mounting evidence suggests that enhancer derived long noncoding RNAs (long ncRNAs), including enhancer RNAs (eRNAs), are an important component of enhancer function, their expression has not been broadly analyzed at a single cell level via imaging techniques. This protocol describes a method to image eRNA in single cells by in situ hybridization followed by tyramide signal amplification (TSA). The procedure can be multiplexed to simultaneously visualize both eRNA and protein-coding transcript at the site of transcriptional elongation, thereby permitting analysis of dynamics between the two transcript species in single cells. Our approach is not limited to eRNAs, but can be implemented on other transcripts. PMID- 27662869 TI - Mapping Long Noncoding RNA Chromatin Occupancy Using Capture Hybridization Analysis of RNA Targets (CHART). AB - Capture Hybridization Analysis of RNA Targets (CHART) has recently been developed to map the genome-wide binding profile of chromatin-associated RNAs. This protocol uses a small number of 22-28 nucleotide biotinylated antisense oligonucleotides, complementary to regions of the target RNA that are accessible for hybridization, to purify RNAs from a cross-linked chromatin extract. RNA chromatin complexes are next immobilized on beads, washed, and specifically eluted using RNase H. Associated genomic DNA is then sequenced using high throughput sequencing technologies and mapped to the genome to identify RNA chromatin associations on a large scale. CHART-based strategies can be applied to determine the nature and extent of long noncoding RNA (long ncRNA) association with chromatin genome-wide and identify direct long ncRNA transcriptional targets. PMID- 27662868 TI - UV-RNA Immunoprecipitation (UV-RIP) Protocol in Neurons. AB - With the many advances in genome-wide sequencing, it has been discovered that much more of the genome is transcribed into RNA than previously appreciated. These nonprotein-coding RNAs (ncRNAs) come in many different forms, and they have been shown to have a variety of functions within the cell, influencing processes such as gene expression, mRNA splicing, and transport, just as a few examples. As we delve deeper into studying their mechanisms of action, it becomes important to understand how they play these roles, in particular by understanding what proteins these ncRNAs interact with. This protocol describes one technique that can be used to study this, ultra-violet light cross-linking RNA immunoprecipitation (UV-RIP), which uses an antibody to pull down a specific protein of interest and then detects RNA that is bound to it. This technique utilizes UV light to cross-link the cells, which takes advantage of the fact that UV light will only cross-link proteins and nucleic acids that are directly interacting. This approach can provide key mechanistic insight into the function of these newly identified ncRNAs. PMID- 27662870 TI - Detecting Long-Range Enhancer-Promoter Interactions by Quantitative Chromosome Conformation Capture. AB - Chromosome conformation capture (3C) technology and its derivatives are currently the primary methodologies measuring contacts among genomic elements. In fact, the lion share of what is currently known about chromosome folding is based on 3C related approaches. For example, distal enhancers are commonly in physically proximity with their target genes, forming chromatin loops. Additional layers of chromatin organization have been described using 3C-based techniques, including topological domains (TADs) and sub-TADs. Finally, inter-chromosomal interactions have been reported although they are much less frequent. 3C is becoming increasingly widespread in its use for understanding genome organization. Here we provide a protocol for quantitative 3C using real-time PCR analysis, along with essential quality controls and normalization methods. PMID- 27662871 TI - Deciphering Noncoding RNA and Chromatin Interactions: Multiplex Chromatin Interaction Analysis by Paired-End Tag Sequencing (mChIA-PET). AB - Genomic DNA is dynamically associated with protein factors and folded to form chromatin fibers. The 3-dimensional (3D) configuration of the chromatin will enable the distal genetic elements to come into close proximity, allowing transcriptional regulation. Noncoding RNA can mediate the 3D structure of chromatin. Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) is a valuable and powerful technique in molecular biology which allows the study of unbiased, genome-wide de novo chromatin interactions with paired-end tags. Here, we describe the standard version of ChIA-PET and a Multiplex ChIA-PET version. PMID- 27662872 TI - Identification of Transcribed Enhancers by Genome-Wide Chromatin Immunoprecipitation Sequencing. AB - Recent work has shown that RNA polymerase II-mediated transcription at distal cis regulatory elements serves as a mark of highly active enhancers. Production of noncoding RNAs at enhancers, termed eRNAs, correlates with higher expression of genes that the enhancer interacts with; hence, eRNAs provide a new tool to model gene activity in normal and disease tissues. Moreover, this unique class of noncoding RNA has diverse roles in transcriptional regulation. Transcribed enhancers can be identified by a common signature of epigenetic marks by overlaying a series of genome-wide chromatin immunoprecipitation and RNA sequencing datasets. A computational approach to filter non-enhancer elements and other classes of noncoding RNAs is essential to not cloud downstream analysis. Here we present a protocol that combines wet and dry bench methods to accurately identify transcribed enhancers genome-wide as well as an experimental procedure to validate these datasets. PMID- 27662873 TI - Global Run-On Sequencing (GRO-Seq). AB - Transcription occurring at gene loci results in accumulation of mature RNA molecules (i.e., mRNAs) that can be easily assayed by RT-PCR or RNA sequencing. However, the steady-state level of RNA does not accurately mirror transcriptional activity per se. In fact, RNA stability plays a major role in determining the relative abundance of any given RNA molecule. Here, I describe a protocol of Nuclear Run-On assay coupled to deep sequencing to assess real-time transcription from engaged RNA polymerase. Mapping nascent transcripts at the genome-wide scale provides a reliable measure of transcriptional activity in mammalian cells and delivers a high-resolution map of coding and noncoding transcripts that is especially useful for annotation and quantification of short-lived RNA molecules. PMID- 27662875 TI - Evaluating the Stability of mRNAs and Noncoding RNAs. AB - Changes in RNA stability have an important impact in the gene expression regulation. Different methods based on the transcription blockage with RNA polymerase inhibitors or metabolic labeling of newly synthesized RNAs have been developed to evaluate RNA decay rates in cultured cell. Combined with techniques to measure transcript abundance genome-wide, these methods have been used to reveal novel features of the eukaryotic transcriptome. The stability of protein coding mRNAs is in general closely associated to the physiological function of their encoded proteins, with short-lived mRNAs being significantly enriched among regulatory genes whereas genes associated with housekeeping functions are predominantly stable. Likewise, the stability of noncoding RNAs (ncRNAs) seems to reflect their functional role in the cell. Thus, investigating RNA stability can provide insights regarding the function of yet uncharacterized regulatory ncRNAs. In this chapter, we discuss the methodologies currently used to estimate RNA decay and outline an experimental protocol for genome-wide estimation of RNA stability of protein-coding and lncRNAs. This protocol details the transcriptional blockage of cultured cells with actinomycin D, followed by RNA isolation at different time points, the determination of transcript abundance by qPCR/DNA oligoarray hybridization, and the calculation of individual transcript half-lives. PMID- 27662874 TI - Computational Approaches for Mining GRO-Seq Data to Identify and Characterize Active Enhancers. AB - Transcriptional enhancers are DNA regulatory elements that are bound by transcription factors and act to positively regulate the expression of nearby or distally located target genes. Enhancers have many features that have been discovered using genomic analyses. Recent studies have shown that active enhancers recruit RNA polymerase II (Pol II) and are transcribed, producing enhancer RNAs (eRNAs). GRO-seq, a method for identifying the location and orientation of all actively transcribing RNA polymerases across the genome, is a powerful approach for monitoring nascent enhancer transcription. Furthermore, the unique pattern of enhancer transcription can be used to identify enhancers in the absence of any information about the underlying transcription factors. Here, we describe the computational approaches required to identify and analyze active enhancers using GRO-seq data, including data pre-processing, alignment, and transcript calling. In addition, we describe protocols and computational pipelines for mining GRO-seq data to identify active enhancers, as well as known transcription factor binding sites that are transcribed. Furthermore, we discuss approaches for integrating GRO-seq-based enhancer data with other genomic data, including target gene expression and function. Finally, we describe molecular biology assays that can be used to confirm and explore further the function of enhancers that have been identified using genomic assays. Together, these approaches should allow the user to identify and explore the features and biological functions of new cell type-specific enhancers. PMID- 27662876 TI - A Novel Method to Quantify RNA-Protein Interactions In Situ Using FMTRIP and Proximity Ligation. AB - RNA binding proteins (RBP) and small RNAs regulate the editing, localization, stabilization, translation, and degradation of ribonucleic acids (RNAs) through their interactions with specific cis-acting elements within target RNAs. Here, we describe a novel method to detect protein-mRNA interactions, which combines FLAG peptide modified, multiply-labeled tetravalent RNA imaging probes (FMTRIPs) with proximity ligation (PLA), and rolling circle amplification (RCA). This assay detects native RNA in a sequence specific and single RNA sensitive manner, and PLA allows for the quantification and localization of protein-mRNA interactions with single-interaction sensitivity. PMID- 27662877 TI - In Silico Promoter Recognition from deepCAGE Data. AB - The accurate identification of transcription start regions corresponding to the promoters of known genes, novel coding, and noncoding transcripts, as well as enhancer elements, is a crucial step towards a complete understanding of state specific gene regulatory networks. Recent high-throughput techniques, such as deepCAGE or single-molecule CAGE, have made it possible to identify the genome wide location, relative expression, and differential usage of transcription start regions across hundreds of different tissues and cell lines. Here, we describe in detail the necessary computational analysis of CAGE data, with focus on two recent in silico methodologies for CAGE peak/profile definition and promoter recognition, namely the Decomposition-based Peak Identification (DPI) and the PROmiRNA software. We apply both methodologies to the challenging task of identifying primary microRNAs transcript (pri-miRNA) start sites and compare the results. PMID- 27662878 TI - Bioinformatics Pipeline for Transcriptome Sequencing Analysis. AB - The development of High Throughput Sequencing (HTS) for RNA profiling (RNA-seq) has shed light on the diversity of transcriptomes. While RNA-seq is becoming a de facto standard for monitoring the population of expressed transcripts in a given condition at a specific time, processing the huge amount of data it generates requires dedicated bioinformatics programs. Here, we describe a standard bioinformatics protocol using state-of-the-art tools, the STAR mapper to align reads onto a reference genome, Cufflinks to reconstruct the transcriptome, and RSEM to quantify expression levels of genes and transcripts. We present the workflow using human transcriptome sequencing data from two biological replicates of the K562 cell line produced as part of the ENCODE3 project. PMID- 27662879 TI - CRISPR/Cas9 Genome Editing in Embryonic Stem Cells. AB - Targeted mutagenesis is required to evaluate the function of DNA segments across the genome. In recent years the CRISPR/Cas9 technology has been widely used for functional genome studies and is partially replacing classical homologous recombination methods in different aspects. CRISPR/Cas9-derived tools indeed allow the production of a wide-range of engineered mutations: from point mutations to large chromosomal rearrangements such as deletions, duplications and inversions. Here we present a protocol to engineer Embryonic Stem Cells (ESC) with desired mutations using transfection of custom-made CRISPR/Cas9 vectors. These methods allow the in vivo modeling of congenital mutations and the functional interrogation of DNA sequences. PMID- 27662880 TI - Targeted Gene Activation Using RNA-Guided Nucleases. AB - The discovery of the prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) system and its adaptation for targeted manipulation of DNA in diverse species has revolutionized the field of genome engineering. In particular, the fusion of catalytically inactive Cas9 to any number of transcriptional activator domains has resulted in an array of easily customizable synthetic transcription factors that are capable of achieving robust, specific, and tunable activation of target gene expression within a wide variety of tissues and cells. This chapter describes key experimental design considerations, methods for plasmid construction, gene delivery protocols, and procedures for analysis of targeted gene activation in mammalian cell lines using CRISPR-Cas transcription factors. PMID- 27662881 TI - Quantitative twoplex glycan analysis using 12C6 and 13C6 stable isotope 2 aminobenzoic acid labelling and capillary electrophoresis mass spectrometry. AB - Capillary electrophoresis (CE) offers excellent efficiency and orthogonality to liquid chromatographic (LC) separations for oligosaccharide structural analysis. Combination of CE with high resolution mass spectrometry (MS) for glycan analysis remains a challenging task due to the MS incompatibility of background electrolyte buffers and additives commonly used in offline CE separations. Here, a novel method is presented for the analysis of 2-aminobenzoic acid (2-AA) labelled glycans by capillary electrophoresis coupled to mass spectrometry (CE MS). To ensure maximum resolution and excellent precision without the requirement for excessive analysis times, CE separation conditions including the concentration and pH of the background electrolyte, the effect of applied pressure on the capillary inlet and the capillary length were evaluated. Using readily available 12/13C6 stable isotopologues of 2-AA, the developed method can be applied for quantitative glycan profiling in a twoplex manner based on the generation of extracted ion electropherograms (EIE) for 12C6 'light' and 13C6 'heavy' 2-AA labelled glycan isotope clusters. The twoplex quantitative CE-MS glycan analysis platform is ideally suited for comparability assessment of biopharmaceuticals, such as monoclonal antibodies, for differential glycomic analysis of clinical material for potential biomarker discovery or for quantitative microheterogeneity analysis of different glycosylation sites within a glycoprotein. Additionally, due to the low injection volume requirements of CE, subsequent LC-MS analysis of the same sample can be performed facilitating the use of orthogonal separation techniques for structural elucidation or verification of quantitative performance. PMID- 27662882 TI - Determination of substituted diphenylamines in environmental samples. AB - Owing to their stability at high temperature, low biodegradation, low water solubility, and low vapor pressure, substituted diphenylamines are used as antioxidants in rubber, foamed polymers, and as high-temperature functional fluids (e.g., lubricants, gear oils, and hydraulic fluids). There are few existing environmental measurements of these substances in any environmental medium. In this study, a method was developed for the determination of 10 substituted diphenylamines in wastewater, biosolids, and sediments using gas chromatography-tandem mass spectrometry (GC-MS/MS). The substituted diphenylamines that were measured were two styrenated diphenylamines isomers, three di-styrenated diphenylamine isomers, tert-butyl-diphenylamine, tert-octyl diphenylamine, di-tert-butyl-diphenylamine, tert-butyl/tert-octyl-diphenylamine, and di-tert-octyl-diphenylamine. The instrument limits of detection (LODs) and limits of quantitation (LOQs) were 0.02-0.1 and 0.06-0.3 ng mL-1, respectively. Target compounds were spiked into sediment, effluent water, influent water, and biosolids at the 100- and 1000-ng levels (N = 6). Analyte recoveries ranged from 71.5 to 117 % with relative standard deviations (RSDs) of 2.12-12.4 %. The method was applied to the analysis of influent, effluent, and biosolid samples; the sum of substituted diphenylamines were 48.1-713, 1.04-28.5 ngL-1, and 85.3-1184 ngg 1dw (median: 71.0, 7.30 ngL-1, and 402 ngg-1dw), respectively. Nine sediment samples collected in Ontario, Canada contained concentrations of the sum of substituted diphenylamines ranging from 1.55 to 897 ngg-1dw. PMID- 27662883 TI - Erratum to: Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry. PMID- 27662885 TI - Health-related quality of life across all stages of autosomal dominant polycystic kidney disease. AB - Background: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease. Methods: A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients. Results: Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5. Conclusions: Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered. PMID- 27662888 TI - Examining Mammography Use by Breast Cancer Risk, Race, Nativity, and Socioeconomic Status. AB - Minority and foreign-born women report lower rates of mammograms compared to non Hispanic white, U.S.-born women, even though they have increased risk for developing breast cancer. We examine disparities in mammography across breast cancer risk groups and determine whether disparities are explained by socioeconomic factors. Propensity score methodology was used to classify individuals from the 2000, 2005, and 2010 National Health Interview Survey according to their risk for developing breast cancer. Logistic regression models were used to predict the likelihood of mammography. Compared to non-Hispanic white women, Mexicans, Asians and "other" racial/ethnic origins were less likely to have undergone a mammogram. After controlling for breast cancer risk, socioeconomic status and health care resources, Mexican, Cuban, Dominican, Central American, Black, and foreign-born women had an increased likelihood of receiving a mammogram. Using propensity scores makes an important contribution to the literature on sub-population differences in the use of mammography by addressing the confounding risk of breast cancer. While other factors related to ethnicity or culture may account for lower breast cancer screening rates in Asian and Mexican women, these findings highlight the need to consider risk, in addition to socioeconomic factors, that may pose barriers to screening in determining mammography disparities. PMID- 27662884 TI - Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies. AB - BACKGROUND: The discovery of novel biomarkers that predict treatment response in advanced cancer patients requires acquisition of high-quality tumor samples. As cancer evolves over time, tissue is ideally obtained before the start of each treatment. Preferably, samples are freshly frozen to allow analysis by next generation DNA/RNA sequencing (NGS) but also for making other emerging systematic techniques such as proteomics and metabolomics possible. Here, we describe the first 469 image-guided biopsies collected in a large collaboration in The Netherlands (Center for Personalized Cancer Treatment) and show the utility of these specimens for NGS analysis. PATIENTS AND METHODS: Image-guided tumor biopsies were performed in advanced cancer patients. Samples were fresh frozen, vital tumor cellularity was estimated, and DNA was isolated after macrodissection of tumor-rich areas. Safety of the image-guided biopsy procedures was assessed by reporting of serious adverse events within 14 days after the biopsy procedure. RESULTS: Biopsy procedures were generally well tolerated. Major complications occurred in 2.1%, most frequently consisting of pain. In 7.3% of the percutaneous lung biopsies, pneumothorax requiring drainage occurred. The majority of samples (81%) contained a vital tumor percentage of at least 30%, from which at least 500 ng DNA could be isolated in 91%. Given our preset criteria, 74% of samples were of sufficient quality for biomarker discovery. The NGS results in this cohort were in line with those in other groups. CONCLUSION: Image-guided biopsy procedures for biomarker discovery to enable personalized cancer treatment are safe and feasible and yield a highly valuable biobank. The Oncologist 2017;22:33 40Implications for Practice: This study shows that it is safe to perform image guided biopsy procedures to obtain fresh frozen tumor samples and that it is feasible to use these biopsies for biomarker discovery purposes in a Dutch multicenter collaboration. From the majority of the samples, sufficient DNA could be yielded to perform next-generation sequencing. These results indicate that the way is paved for consortia to prospectively collect fresh frozen tumor tissue. PMID- 27662889 TI - A Within-Subjects Analysis of Men's Alcohol-Involved and Nonalcohol-Involved Sexual Assaults. AB - Previous research has determined that alcohol use is frequently associated with sexual aggression perpetration. However, little research has examined the differences between alcohol-involved and nonalcohol-involved assaults among men who are repeat perpetrators of sexual aggression. Eighty men from the community who had self-reported perpetration of two or more sexual assaults, including at least one assault in which the participant was drinking and one assault in which they were sober, were recruited for a within-subjects survey. Data analysis examined the differences between participants' most recent alcohol-involved assault and their most recent nonalcohol-involved assault. A variety of differences were observed between nonalcohol and alcohol-involved assaults including the participants' primary appraisals, secondary appraisals, and the degree of force they used to obtain unwanted sex. These results provide further insight into the effect that alcohol has on perpetration of sexual aggression. Limitations and directions for future research are also discussed. PMID- 27662886 TI - Heightened early-attentional stimulus orienting and impulsive action in men with antisocial personality disorder. AB - We tested whether enhanced stimulus orienting operationalized as N1 and P2 auditory evoked potentials to increasing loudness (50-90 dB clicks) could be associated with trait impulsivity (Barratt Impulsiveness Scale, BIS-11), impulsive action (commission error on the Immediate Memory Task), or impulsive choice (immediate responses on temporal discounting tasks). We measured N1 and P2 loudness sensitivity in a passive listening task as linear intensity-sensitivity slopes in 36 men with antisocial personality disorder with a history of conviction for criminal conduct and 16 healthy control men. Across all subjects, regression analyses revealed that a steeper P2 slope predicted higher IMT commission error/correct detection ratio, and lower stimulus discriminability (A prime). These associations were also found within both groups. These relationships suggest an association between enhanced early stimulus orienting (P2), impulsive action (response inhibition), and impaired signal-noise discriminability (A-prime). PMID- 27662890 TI - Urinary tract infections in adults. AB - A urinary tract infection (UTI) is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. The incidence of UTIs in adult males aged under 50 years is low, with adult women being 30 times more likely than men to develop a UTI. Appropriate classification of UTI into simple or complicated forms guides its management and the ORENUC classification can be used. Diagnosis of a UTI is based on a focused history, with appropriate investigations depending on individual risk factors. Simple uncomplicated cystitis responds very well to oral antibiotics, but complicated UTIs may require early imaging, and referral to the emergency department or hospitalisation to prevent urosepsis may be warranted. Escherichia coli remains the predominant uropathogen in acute community-acquired uncomplicated UTIs and amoxicillin-clavulanate is useful as a first-line antibiotic. Family physicians are capable of managing most UTIs if guided by appropriate history, investigations and appropriate antibiotics to achieve good outcomes and minimise antibiotic resistance. PMID- 27662891 TI - Gender Difference in the Risk of Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography or Percutaneous Coronary Intervention. AB - Contrast-induced nephropathy (CIN) is a common complication of coronary angiography/percutaneous coronary intervention (PCI). Identification of high-risk patients and optimal periprocedural management are key points to reduce the incidence of this iatrogenic complication. We evaluated the impact of gender on CIN after coronary angiography/PCI. We enrolled 2851 consecutive patients (730 females and 1851 males) undergoing coronary angiography/PCI. Baseline clinical and procedural characteristics were collected according to gender. CIN was defined as an absolute >=0.5mg/dL or a relative >=25% increase in creatinine level 24 to 48 hours after the procedure. The incidence of CIN was 12.6% and was significantly higher among females (15.6% vs 11.4%, odds ratio (OR) [95% confidence interval (CI)] = 1.42 [1.11-1.82]; P = .004), but this result was not confirmed at multivariate analysis after correction for all baseline confounders (adjusted OR [95% CI] = 1.14 [0.81-1.60]; P = 0.45). In conclusion, we showed that female gender is associated with an increased risk of CIN after coronary angiography/PCI. However, this finding was not confirmed after correction for baseline confounders. Therefore, the higher risk profile rather than female gender itself may contribute to the higher occurrence of CIN among women. PMID- 27662892 TI - Single-Stage Bipedicle Local Tissue Transfer and Skin Graft for Achilles Tendon Surgery Wound Complications. AB - INTRODUCTION: Achilles tendon and posterior heel wound complications are difficult to treat. These typically require soft tissue coverage via microvascular free tissue transfer at a tertiary referral center. Here, we describe coverage of a series of posterior heel and Achilles wounds via simple, local tissue transfer, called a bipedicle fasciocutaneous flap. This flap can be performed by an orthopaedic foot and ankle surgeon, without resources of tertiary/specialized care or microvascular support. METHODS: Three patients with separate pathologies were treated with a single-stage bipedicle fasciocutaneous local tissue transfer. Case 1 was a patient with insertional wound breakdown after Achilles debridement and repair to the calcaneus. Case 2 was a heel venous stasis ulcer with calcaneal exposure in a diabetic patient with vasculopathy. Case 3 was a patient with wound breakdown following midsubstance Achilles tendon repair. All three cases were treated with a single-stage bipedicle local tissue transfer for posterior ankle and heel wound complications. RESULTS: All 3 patients demonstrated complete healing of the posterior defect, lateral ankle skin graft recipient site, and the skin graft donor site after surgery. Case 3 had a subsequent recurrent ulceration after initial healing. This was superficial and healed with local wound care. All patients regained full preoperative range of motion and were able to ambulate independently without modified footwear. CONCLUSIONS: The bipedicled fasciocutaneous flap described here offers a predictable single stage procedure that can be accomplished by an orthopaedic foot and ankle surgeon without resources of a tertiary care center for posterior foot and ankle defects. This flap can be performed with short operative times and can be customized to facilitate defect coverage. The flap is durable to withstand local tissue stresses required for early ambulation. Despite its reliability, patients require careful follow-up to manage underlying comorbid conditions that may complicate wound healing. LEVELS OF EVIDENCE: Level IV: Case series. PMID- 27662893 TI - Rethinking primary care's gatekeeper role. PMID- 27662894 TI - Evidence-based treatments for youths with severely dysregulated mood: a qualitative systematic review of trials for SMD and DMDD. AB - The aim of this literature review was to examine the evidence for psychotherapeutic and pharmacological treatments in subjects with severely dysregulated mood and to identify potential areas for improvements in research designs. A literature search was conducted using several databases for published (PubMed, PsycINFO) and ongoing (clinical trial registries) studies conducted in youths who met NIMH's criteria for Severe Mood Dysregulation (SMD) or the DSM-5 diagnosis of Disruptive Mood Dysregulation Disorder (DMDD). Eight completed studies were identified: three randomized trials, four open pilot studies and one case report. Seven ongoing studies were found in trial registries. The available evidence suggests potential efficacy of psychotherapies which have previously been developed for internalizing and externalizing disorders. The two main pharmacological strategies tested are, first, a monotherapy of psychostimulant or atypical antipsychotic such as risperidone, already used in the treatment of severe irritability in youths with developmental disorders; and second, the use of a serotonergic antidepressant as an add-on therapy in youths treated with psychostimulant. Ongoing studies will further clarify the effectiveness of psychotherapeutic interventions for DMDD individuals and whether they should be given alone or in conjunction with other treatments. The short duration of the trials for a chronic disorder, the low number of studies, the lack of placebo or active comparator arm, and restrictive inclusion criteria in most of the controlled trials dramatically limit the interpretation of the results. Finally, future research should be conducted across multiple sites, with standardized procedures to measure DMDD symptoms reduction, and include a run-in period to limit placebo effect. PMID- 27662895 TI - Toward a Mechanistic Understanding of Epileptic Networks. AB - Focal epileptic seizures have long been considered to arise from a small susceptible brain area and spread through uninvolved regions. In the past decade, the idea that focal seizures instead arise from coordinated activity across large scale epileptic networks has become widely accepted. Understanding the network model's applicability is critical, due to its increasing influence on clinical research and surgical treatment paradigms. In this review, we examine the origins of the concept of epileptic networks as the nidus for recurring seizures. We summarize analytical and methodological elements of epileptic network studies and discuss findings from recent detailed electrophysiological investigations. Our review highlights the strengths and limitations of the epileptic network theory as a metaphor for the complex interactions that occur during seizures. We present lines of investigation that may usefully probe these interactions and thus serve to advance our understanding of the long-range effects of epileptiform activity. PMID- 27662897 TI - TRANSPORTIN1 Promotes the Association of MicroRNA with ARGONAUTE1 in Arabidopsis. AB - In Arabidopsis thaliana, microRNAs (miRNAs) are mainly loaded into ARGONAUTE1 (AGO1) to posttranscriptionally regulate gene expression. We previously found that ENHANCED MiRNA ACTIVITY1 (EMA1), an importin beta family protein, negatively regulates miRNA loading into AGO1. In this study, through a suppressor screening of ema1, we identified another importin beta protein, TRANSPORTIN1 (TRN1), as a regulatory component in the miRNA pathway. Mutation of TRN1 did not reduce miRNA accumulation, but it impaired miRNA activity. We found that TRN1 interacted with AGO1. Mutation of the three conserved residues required for cargo recognition of TRN1 reduced its interaction with AGO1 and compromised its function in regulating miRNA activity. Intriguingly, TRN1 dysfunction did not change the cytoplasmic nuclear distribution of miRNAs and AGO1 but reduced the amount of miRNAs associated with AGO1. These results indicate that TRN1 positively regulates miRNA activity by promoting the association of miRNAs with AGO1, and they reveal opposing roles of two importin beta family proteins in miRNA loading. PMID- 27662896 TI - Hypothalamic Dysfunction and Multiple Sclerosis: Implications for Fatigue and Weight Dysregulation. AB - Signs and symptoms of multiple sclerosis are usually attributed to demyelinating lesions in the spinal cord or cerebral cortex. The hypothalamus is a region that is often overlooked yet controls many important homeostatic functions, including those that are perturbed in multiple sclerosis. In this review we discuss how hypothalamic dysfunction may contribute to signs and symptoms in people with multiple sclerosis. While dysfunction of the hypothalamic-pituitary-adrenal axis is common in multiple sclerosis, the effects and mechanisms of this dysfunction are not well understood. We discuss three hypothalamic mechanisms of fatigue in multiple sclerosis: (1) general hypothalamic-pituitary-adrenal axis hyperactivity, (2) disordered orexin neurotransmission, (3) abnormal cortisol secretion. We then review potential mechanisms of weight dysregulation caused by hypothalamic dysfunction. Lastly, we propose future studies and therapeutics to better understand and treat hypothalamic dysfunction in multiple sclerosis. Hypothalamic dysfunction appears to be common in multiple sclerosis, yet current studies are underpowered and contradictory. Future studies should contain larger sample sizes and standardize hormone and neuropeptide measurements. PMID- 27662898 TI - Characterization of Biosynthetic Pathways for the Production of the Volatile Homoterpenes DMNT and TMTT in Zea mays. AB - Plant volatiles not only have multiple defense functions against herbivores, fungi, and bacteria, but also have been implicated in signaling within the plant and toward other organisms. Elucidating the function of individual plant volatiles will require more knowledge of their biosynthesis and regulation in response to external stimuli. By exploiting the variation of herbivore-induced volatiles among 26 maize (Zea mays) inbred lines, we conducted a nested association mapping and genome-wide association study (GWAS) to identify a set of quantitative trait loci (QTLs) for investigating the pathways of volatile terpene production. The most significant identified QTL affects the emission of (E) nerolidol, linalool, and the two homoterpenes (E)-3,8-dimethyl-1,4,7-nonatriene (DMNT) and (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT). GWAS associated a single nucleotide polymorphism in the promoter of the gene encoding the terpene synthase TPS2 with this QTL Biochemical characterization of TPS2 verified that this plastid-localized enzyme forms linalool, (E)-nerolidol, and (E,E)-geranyllinalool. The subsequent conversion of (E)-nerolidol into DMNT maps to a P450 monooxygenase, CYP92C5, which is capable of converting nerolidol into DMNT by oxidative degradation. A QTL influencing TMTT accumulation corresponds to a similar monooxygenase, CYP92C6, which is specific for the conversion of (E,E) geranyllinalool to TMTT The DMNT biosynthetic pathway and both monooxygenases are distinct from those previously characterized for DMNT and TMTT synthesis in Arabidopsis thaliana, suggesting independent evolution of these enzymatic activities. PMID- 27662899 TI - Nucleosomal signatures impose nucleosome positioning in coding and noncoding sequences in the genome. AB - In the yeast genome, a large proportion of nucleosomes occupy well-defined and stable positions. While the contribution of chromatin remodelers and DNA binding proteins to maintain this organization is well established, the relevance of the DNA sequence to nucleosome positioning in the genome remains controversial. Through quantitative analysis of nucleosome positioning, we show that sequence changes distort the nucleosomal pattern at the level of individual nucleosomes in three species of Schizosaccharomyces and in Saccharomyces cerevisiae This effect is equally detected in transcribed and nontranscribed regions, suggesting the existence of sequence elements that contribute to positioning. To identify such elements, we incorporated information from nucleosomal signatures into artificial synthetic DNA molecules and found that they generated regular nucleosomal arrays indistinguishable from those of endogenous sequences. Strikingly, this information is species-specific and can be combined with coding information through the use of synonymous codons such that genes from one species can be engineered to adopt the nucleosomal organization of another. These findings open the possibility of designing coding and noncoding DNA molecules capable of directing their own nucleosomal organization. PMID- 27662901 TI - Myeloperoxidase as a Potential Target in Women With Endometriosis Undergoing IVF. AB - As infertility is intimately associated with endometriosis, the levels of myeloperoxidase (MPO), a leukocyte enzyme and an oxidative stress marker, were determined in a case-control prospective study of 68 women with and without endometriosis undergoing in vitro fertilization in the outpatient fertility center within a tertiary care academic medical center. Measured values included plasma and follicular fluid (FF) concentrations of MPO, plasma estradiol, as well as oocyte quality, fertilization, implantation, and pregnancy rates in these women. In FF (mean +/- standard error of mean [SEM]), the MPO concentrations (ng/mL) for controls were 4.3 +/- 0.37, mild endometriosis (stages I-II) 3.9 +/- 0.17, and moderate/severe endometriosis (stages III-IV) 16.6 +/- 12.5 ( P < 0.0143). In FF, among patients supplemented with vitamins E and C, the MPO levels decreased significantly only in moderate/severe endometriosis from 25.3 +/- 22.0 ng/mL to 4.9 +/- 1.61 ng/mL, respectively. Plasma levels of MPO between groups did not change. Outcome data revealed a trend toward decreased percentage of mature oocytes, implantation rate, and clinical pregnancy rate with severity of endometriosis and MPO levels. Myeloperoxidase may be a potential oxidative stress target for endometriosis-associated infertility. PMID- 27662900 TI - Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently. AB - Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires' disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 from the five disease-associated STs and 27 representative of the species diversity. Phylogenetic analyses revealed that the five STs have independent origins within a highly diverse species. The number of de novo mutations is extremely low with maximum pairwise single-nucleotide polymorphisms (SNPs) ranging from 19 (ST47) to 127 (ST1), which suggests emergences within the last century. Isolates sampled geographically far apart differ by only a few SNPs, demonstrating rapid dissemination. These five STs have been recombining recently, leading to a shared pool of allelic variants potentially contributing to their increased disease propensity. The oldest clone, ST1, has spread globally; between 1940 and 2000, four new clones have emerged in Europe, which show long-distance, rapid dispersal. That a large proportion of clinical cases is caused by recently emerged and internationally dispersed clones, linked by convergent evolution, is surprising for an environmental bacterium traditionally considered to be an opportunistic pathogen. To simultaneously explain recent emergence, rapid spread and increased disease association, we hypothesize that these STs have adapted to new man-made environmental niches, which may be linked by human infection and transmission. PMID- 27662902 TI - RHOG-DOCK1-RAC1 Signaling Axis Is Perturbed in DHEA-Induced Polycystic Ovary in Rat Model. AB - The function of RHOG, a RAC1 activator, was explored in the ovary during ovarian follicular development and pathological conditions. With the help of immunoblotting and immunolocalization, we determined the expression and localization of RHOG in normal (estrous cycle) and polycystic ovaries using Sprague Dawley (SD) rat model. Employing polymerase chain reaction and flow cytometry, we analyzed the transcript and expression levels of downstream molecules of RHOG, DOCK1, and RAC1 in the polycystic ovarian syndrome (PCOS) ovary along with normal antral follicular theca and granulosa cells after dehydroepiandrosterone (DHEA) supplementation. The effect of RHOG knockdown on DOCK1, VAV, and RAC1 expression was evaluated in the human ovarian cells (SKOV3), theca cells, and granulosa cells from SD rats with the help of flow cytometry. Oocyte at secondary follicles along with stromal cells showed optimal expression of RHOG. Immunoblotting of RHOG revealed its maximum expression at diestrus and proestrus, which was downregulated at estrus stage. Mild immunostaining of RHOG was also present in the theca and granulosa cells of the secondary and antral follicles. Polycystic ovary exhibited weak immunostaining for RHOG and that was corroborated by immunoblotting-based investigations. RHOG effectors DOCK1 and ELMO1 were found reduced in the ovary in PCOS condition/DHEA. RHOG silencing reduced the expression of DOCK1 and RAC1 in the theca and granulosa cells from SD rat antral follicles and that was mirrored in the human ovarian cells. Collectively, RHOG can mediate signaling through downstream effectors DOCK1 and RAC1 during ovarian follicular development (theca and granulosa cells and oocyte), but DHEA downregulated them in the PCOS ovary. PMID- 27662903 TI - Insulin Exhibits an Antiproliferative and Hypertrophic Effect in First Trimester Human Extravillous Trophoblasts. AB - Our aim was to investigate the effect of high levels of glucose, insulin, leptin, and tumor necrosis factor alpha, biomarkers of diabetes in pregnancy, in the process of placentation, using as a cell model a first trimester extravillous human trophoblast cell line (HTR8/SVneo cells). Exposure of HTR8/SVneo cells for 24 hours to either glucose (20 mmol/L) or leptin (25-100 ng/mL) did not cause significant changes in cell proliferation and viability. Tumor necrosis factor alpha (24 hours; 10-100 ng/L) caused a small decrease (10%) in cell proliferation and an increase (9%) in cell viability; however, both effects disappeared when exposure time was increased. Insulin (24 hours; 1-10 nmol/L) caused a concentration- and time-dependent decrease (10%-20%) in cell proliferation; the effect of insulin (10 nmol/L) was more pronounced after a 48 hours exposure (35%). In contrast, exposure to insulin (10 nmol/L; 48 hours) showed no significant effect on cell viability, apoptosis, and migration capacity. Insulin appears to cause hypertrophy of HTR8/SVneo cells as it reduces the cell mitotic index while increasing the culture protein content. The antiproliferative effect of insulin seems to involve activation of mammalian target of rapamycin, phosphoinositide 3-kinase, and p38 mitogen-activated protein kinase. Finally, simvastatin and the polyphenol quercetin potentiated the antiproliferative effect of insulin; on the contrary, the polyphenol resveratrol, the polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids, and folic acid were not able to change it. In conclusion, we show that insulin has an antiproliferative and hypertrophic effect on a first trimester extravillous human trophoblast cell line. So insulin might affect the process of placentation. PMID- 27662905 TI - Fenofibrate Decreases Insulin Clearance and Insulin Secretion to Maintain Insulin Sensitivity. AB - High fat diet reduces the expression of CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a transmembrane glycoprotein that promotes insulin clearance and down-regulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator activated receptor alpha (PPARalpha) transcriptionally suppresses CEACAM1 expression, we herein examined whether high fat down-regulates CEACAM1 expression in a PPARalpha-dependent mechanism. By activating PPARalpha, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation. Despite reducing glucose stimulated insulin secretion, fenofibrate treatment does not result in insulin insufficiency. To examine whether this is mediated by a parallel decrease in CEACAM1-dependent hepatic insulin clearance pathways, we fed wild-type and Pparalpha-/- null mice a high fat diet supplemented with either fenofibrate or Wy14643, a selective PPARalpha agonist, and examined their effect on insulin metabolism and action. We demonstrated that the decrease in insulin secretion by fenofibrate and Wy14643 is accompanied by reduction in insulin clearance in wild type but not Pparalpha-/- mice, thereby maintaining normoinsulinemia and insulin sensitivity despite continuous high fat intake. Intact insulin secretion in L-CC1 mice with protected hepatic insulin clearance and CEACAM1 levels provides in vivo evidence that insulin secretion responds to changes in insulin clearance to maintain physiologic insulin and glucose homeostasis. These results also emphasize the relevant role of hepatic insulin extraction in regulating insulin sensitivity. PMID- 27662906 TI - Overlapping Role of Respiratory Supercomplex Factor Rcf2 and Its N-terminal Homolog Rcf3 in Saccharomyces cerevisiae. AB - The mitochondrial electron transport chain consists of individual protein complexes arranged into large macromolecular structures, termed respiratory chain supercomplexes or respirasomes. In the yeast Saccharomyces cerevisiae, respiratory chain supercomplexes form by association of the bc1 complex with the cytochrome c oxidase. Formation and maintenance of these assemblies are promoted by specific respiratory supercomplex factors, the Rcf proteins. For these proteins a regulatory function in bridging the electron transfer within supercomplexes has been proposed. Here we report on the maturation of Rcf2 into an N- and C-terminal peptide. We show that the previously uncharacterized Rcf3 (YBR255c-A) is a homolog of the N-terminal Rcf2 peptide, whereas Rcf1 is homologous to the C-terminal portion. Both Rcf3 and the C-terminal fragment of Rcf2 associate with monomeric cytochrome c oxidase and respiratory chain supercomplexes. A lack of Rcf2 and Rcf3 increases oxygen flux through the respiratory chain by up-regulation of the cytochrome c oxidase activity. A double gene deletion of RCF2 and RCF3 affects cellular survival under non-fermentable growth conditions, suggesting an overlapping role for both proteins in the regulation of the OXPHOS activity. Furthermore, our data suggest an association of all three Rcf proteins with the bc1 complex in the absence of a functional cytochrome c oxidase and identify a supercomplex independent interaction network of the Rcf proteins. PMID- 27662904 TI - A Novel Conserved Domain Mediates Dimerization of Protein Kinase D (PKD) Isoforms: DIMERIZATION IS ESSENTIAL FOR PKD-DEPENDENT REGULATION OF SECRETION AND INNATE IMMUNITY. AB - Protein kinase D (PKD) isoforms are protein kinase C effectors in signaling pathways regulated by diacylglycerol. Important physiological processes (including secretion, immune responses, motility, and transcription) are placed under diacylglycerol control by the distinctive substrate specificity and subcellular distribution of PKDs. Potentially, broadly co-expressed PKD polypeptides may interact to generate homo- or heteromultimeric regulatory complexes. However, the frequency, molecular basis, regulatory significance, and physiological relevance of stable PKD-PKD interactions are largely unknown. Here, we demonstrate that mammalian PKDs 1-3 and the prototypical Caenorhabditis elegans PKD, DKF-2A, are exclusively (homo- or hetero-) dimers in cell extracts and intact cells. We discovered and characterized a novel, highly conserved N terminal domain, comprising 92 amino acids, which mediates dimerization of PKD1, PKD2, and PKD3 monomers. A similar domain directs DKF-2A homodimerization. Dimerization occurred independently of properties of the regulatory and kinase domains of PKDs. Disruption of PKD dimerization abrogates secretion of PAUF, a protein carried in small trans-Golgi network-derived vesicles. In addition, disruption of DKF-2A homodimerization in C. elegans intestine impaired and degraded the immune defense of the intact animal against an ingested bacterial pathogen. Finally, dimerization was indispensable for the strong, dominant negative effect of catalytically inactive PKDs. Overall, the structural integrity and function of the novel dimerization domain are essential for PKD-mediated regulation of a key aspect of cell physiology, secretion, and innate immunity in vivo. PMID- 27662909 TI - No trust in trusts. AB - 'Our staff are our greatest asset', declared the Guy's and Lewisham Trust in its consultation document published in August last year. So why, only weeks into Trust status, did it announce massive job cuts? It's difficult to imagine that the Chief Executive was completely unaware of the devastating impact such news would have on staff morale. Any attempts now to lessen the blow by claiming fewer redundancies are futile. Staff and public confidence in Trusts has plummeted. People needed to believe that Trusts were a better option. While many nurses had reservations about the philosophy of the internal market, they retained an open mind about a number of issues related to the reforms. There are few who will stand and defend any aspect of the changes now. PMID- 27662908 TI - Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography. AB - OBJECTIVE: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. METHODS: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow Lyon voltage combination or Cornell voltage-duration product (absolute value/cut off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography. RESULTS: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p < .0001, and odds ratio: 1.21 per 0.10 (95% CI: 1.02-1.42), p = .03). In addition, discrepancy was also seen in females and subjects receiving antihypertensive medication (odds ratio: 1.41 (95% CI: 1.04-1.89), p = .03 and odds ratio: 1.41 (95% CI: 1.06-1.87), p = .02), but FPG did not independently influence discrepancy between ECG and echocardiography. CONCLUSION: Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non consistency between LVH determined by ECG and echocardiography. PMID- 27662907 TI - Polo-like Kinase 1 Regulates Vimentin Phosphorylation at Ser-56 and Contraction in Smooth Muscle. AB - Polo-like kinase 1 (Plk1) is a serine/threonine-protein kinase that has been implicated in mitosis, cytokinesis, and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor. Moreover, knockdown of Plk1 in smooth muscle attenuated force development. Smooth muscle conditional knock-out of Plk1 also diminished contraction of mouse tracheal rings. Plk1 knockdown inhibited acetylcholine-induced vimentin phosphorylation at Ser-56 without affecting myosin light chain phosphorylation. Expression of T210A Plk1 inhibited the agonist-induced vimentin phosphorylation at Ser-56 and contraction in smooth muscle. However, myosin light chain phosphorylation was not affected by T210A Plk1. Ste20-like kinase (SLK) is a serine/threonine-protein kinase that has been implicated in spindle orientation and microtubule organization during mitosis. In this study knockdown of SLK inhibited Plk1 phosphorylation at Thr-210 and activation. Finally, asthma is characterized by airway hyperresponsiveness, which largely stems from airway smooth muscle hyperreactivity. Here, smooth muscle conditional knock-out of Plk1 attenuated airway resistance and airway smooth muscle hyperreactivity in a murine model of asthma. Taken together, these findings suggest that Plk1 regulates smooth muscle contraction by modulating vimentin phosphorylation at Ser-56. Plk1 activation is regulated by SLK during contractile activation. Plk1 contributes to the pathogenesis of asthma. PMID- 27662911 TI - NHS Policy board. AB - Nurse representation on the NF1S Policy Board is likely to double by the end of the year, Health Secretary William Waldegrave has indicated. PMID- 27662910 TI - ? AB - Major protest: Staff at Guy's Hospital lobbied a meeting of the Trust Management Board to discuss job cuts last week. Around 50 staff took part. PMID- 27662912 TI - Guy's reduces its job loss figures. AB - Guy's Hospital Trust shrank its 600 staff job axe figure last week, announcing nine nurse redundancies, 21 lost nursing posts and 19 closed beds. PMID- 27662914 TI - Redundancies. AB - Staff at Hammersmith Hospital are in dispute over management's refusal to disclose the criteria used to identify 37 posts for redundancy. PMID- 27662913 TI - 'Steady trickle' of responses to initiative. AB - The Royal College of Nursing has received a 'steady trickle' of responses from nurses and the public in response to General Secretary Christine Hancock's 'whistleblow' initiative. PMID- 27662916 TI - Surveillance. AB - The RCN has lashed out at a cash-starved health authority which paid two private investigators to follow a nurse tutor on sick leave for two months. PMID- 27662915 TI - ? AB - Care team: More than 40 representatives front health and local authorities took part in the Care Kaleidoscope project to simulate the Government's new community care arrangements. The findings are due to be published by South West Thames Region later this month. PMID- 27662917 TI - RCN to ballot members. AB - The RCN is to ballot its members on whether nursing health care assistants should be granted full membership. 'We are now into 1991. We have got to move forward,' explained Council member, Stuart Mahon. PMID- 27662918 TI - ? AB - The RCN launched a new leaflet 'Working with Women' at its Congress in Harrogate. The leaflet includes a questionnaire inviting nurses to outline the areas which they believe should be priorities for the College's Women's Issues Committee. PMID- 27662919 TI - Smith & Nephew awards. AB - The Smith & Nephew Foundation has announced the winners of its Primary Care Awards, aimed at nurses working in the community to allow them to improve their clinical skills and expertise. PMID- 27662920 TI - New guidelines deal with abuse by informal carers. AB - Nurses must be prepared to offer support to both victim and perpetrator in cases of abuse of elderly people, new Royal College of Nursing guidelines advise. PMID- 27662921 TI - Testing in prisons to 'enable comparisons'. AB - Anonymous HIV testing of prisoners attending prison genito-urinary clinics is expected to be introduced shortly, the Prisons Minister Angela Rumbold, revealed last week. PMID- 27662922 TI - ? AB - Peggy Prior of the Work-injured Nurses' Group led the field during a sponsored 'Jog for Romania' on the final morning of the RCN Congress in Harrogate. PMID- 27662925 TI - Staff to meet employers over appeals backlog. AB - The Staff Side of the nurses and midwives' negotiating body is to meet management on Friday to discuss the huge backlog of clinical grading appeals. PMID- 27662924 TI - COHSE welcomes Scottish hotel-class initiative. AB - COHSE has welcomed Government calls to introduce 'patient hotels' in Scotland to replace hospital facilities. PMID- 27662926 TI - Health Care Assistants. AB - Congress voted to ensure the proper role and function of the nurse is promoted and that health care assistants continue to support that role. PMID- 27662927 TI - MP complains of 'poor-quality' business plans. AB - Business plans put forward by many of the applicants in the first wave of NHS Trusts were so poor that they would not get through a school management committee, Labour MP Alice Mahon told a Congress Question Time audience. PMID- 27662928 TI - Call for national review of hospital security. AB - A national review of hospital security is urgently needed to tackle the growing problem of violent attacks on staff and patients, Congress agreed. PMID- 27662929 TI - Royal college of nursing congress. AB - Health Secretary William Waldegrave's assurances that the Review Body on nurses' pay is secure may not be enough to guarantee the future of national pay bargaining, Congress decided. PMID- 27662930 TI - ? AB - The reports of RCN working parties into total quality management, nursing leadership and occupational health and safety issues in the European Communities were launched. PMID- 27662931 TI - Fully resourcing and implementing PREPP. AB - Full Government funding to allow the implementation of the Post-registration Education and Practice Project (PREPP) was urged by Congress. PMID- 27662932 TI - Racial Equality. AB - Health care employers are to be urged to adopt racial equality employment policies to increase fair recruitment after a resolution was passed unanimously. PMID- 27662933 TI - Tackling discrimination in job advertisements. AB - Congress wants to stop the discrimination between first- and second-level nurses in job advertisements under the clinical grading structure. PMID- 27662934 TI - ? AB - Nurse and author Winifred Hector was awarded an honorary Doctor of Science degree by City University recently in recognition of her lifetime's contribution to the nursing profession. She is pictured with musician Peter Gabriel who was awarded an honorary degree at the same Foundation Day ceremony. PMID- 27662936 TI - Parliament. AB - Labour attacks on the state of the NHS are damaging nursing morale, Health Secretary William Waldegrave claimed last week. In response, Shadow Health Secretary Robin Cook has dismissed the allegation, claiming that any decline has been caused by Government policies. PMID- 27662937 TI - ? AB - Cheers, John: Man Jordan, South Western Area Liaison Staff Officer for the St John Ambulance, was invested into the Order of St John in recognition of her 20 years service with the organisation. Mrs Jordan works as a Property and Services Officer with the Royal College of Nursing. PMID- 27662939 TI - World news. AB - What's happening in nursing across the globe. PMID- 27662940 TI - ? AB - Getting the massage: Steve Bird demonstrates a massage therapy chair with nurse Emma Reed at the recent International Festival for Mind, Body and Spirit. PMID- 27662941 TI - Vitamin E could help reduce heart problems. AB - Extra doses of vitamin E could help people on cholesterol-lowering drugs to reduce their risk of heart problems, a biochemist at King's College has suggested. PMID- 27662942 TI - 'No smoking in taxis' boosts HEA campaign. AB - The Health Education Authority launched a 'no smoking in taxis' campaign last week to mark World No Tobacco Day. PMID- 27662943 TI - Menstrual cycles and cancer surgery. AB - The long-term outlook for premenopausal women with breast cancer is greatly improved if they have their operation in the second half of their menstrual cycle, research shows. PMID- 27662944 TI - Hospital closures result in anxiety. AB - Nurses affected by the closure of large psychiatric hospitals, as patients are transferred into the community, experience feelings of grief, anxiety and loss, according to recent research. PMID- 27662945 TI - Abdominal surgery may result in gallstones. AB - Major abdominal surgery might accelerate the formation of gallstones. PMID- 27662946 TI - Antiemetic used for schizophrenia. AB - Ondansetron, marketed for the treatment of cytotoxic drug-induced emesis, might be useful in the treatment of schizophrenia, researchers say. PMID- 27662947 TI - Achieving targeted screening rates. AB - Opportunistic screening methods are unlikely to achieve desired screening rates within acceptable time limits, researchers say. PMID- 27662948 TI - Spec-tacular aid to hearing impaired. AB - Prototype devices which filter out background noise and could be of use to the hearing impaired have been developed. PMID- 27662949 TI - Advice needed in use of home nebulisers. AB - Home nebulisers are valuable in childhood asthma but parents should be given written, as well as verbal, user- instructions, especially in the management of severe attacks. PMID- 27662950 TI - Parlez-vous Francais? AB - 'The Italians are a nation of hypochondriacs, the Germans treat illness the rest of Europe has never heard of, and the French are obsessed with the state of their livers. Britons swallow more laxatives than the rest of Europe put together, and seek treatment for diarrhoea more often than our continental neighbours.' PMID- 27662951 TI - Meet the panelLinda Thomas introduces the panel of eight judges who will be choosing the winners of the Nursing Standard/ BUPA Nursing Nurse 91 Awards. AB - Your entries are flooding in for the prestigious Nursing Standard/ BUVA Nursing Nurse 91 Awards. From the quality of the entries we have already received, it looks as if the judging panel has a difficult task ahead in identifying this year's winners. PMID- 27662952 TI - ? AB - " Mr Smith's complaining about his food again". PMID- 27662953 TI - Super-nurse grounded. AB - I would like to thank the Government for the introduction of the 'super-nurse' to reduce medical staffs huge work loads. PMID- 27662954 TI - No more heroes. AB - What is a nurse and what is a super-nurse? PMID- 27662955 TI - Definition of roles. AB - I was interested to read the letter from David Nance (Nursing Standard May 22) concerning the attitude of the unit general manager at Somerset towards registered nurses working with mentally handicapped. PMID- 27662956 TI - Androgogy rules ok? AB - I was surprised by Philip Burnard's article, Students as Adults? (Nursing Standard May 22). I checked the year, but yes it was 1991, not 1951. PMID- 27662957 TI - ? PMID- 27662958 TI - Improving radiotherapy. AB - 'Giving information to radiotherapy patients' (Nursing Standard May 15) brought back vivid memories of my emotions and experiences of radiotherapy following a mastectomy eight years ago. PMID- 27662959 TI - Seeking assistance. AB - I would like to appeal to all hospitals in the UK for assistance. PMID- 27662960 TI - Clinical Nursing Skills and Techniques, 2nd edition A Perry and P Poller Clinical Nursing Skills and Techniques, 2nd edition C V Mosby 1,064pp L34.25 0-8016-5493-9 [Formula: see text]. AB - Clinical Nursing Skills and Techniques is intended for both qualified and student nurse levels as a reference text, and I feel that the book certainly achieves its aim. It is an in-depth text with a broad range of subjects in 47 chapters. PMID- 27662961 TI - Working in the Operating Theatre B Kumar Working in the Operating Theatre Churchill Livingstone 272pp L14.95 0-443-03908-9 [Formula: see text]. AB - Bakul Kumar aims to provide a 'comprehensive, straightforward text' to meet 'the needs of those undertaking studies in anaesthetic and operating department nursing, as well as those training as hospital operating department assistants'. The subjects include anatomy and physiology, pharmacology, acid-base balance, patient care, theatre technique, among others, with multiple choice questions for revision purposes. PMID- 27662965 TI - Bettering one's self? AB - I suppose I should have learned from the fiascos I have experienced in almost four ' years of general student nurse training. PMID- 27662963 TI - A small step in the right direction. AB - We have freed the log jam at last. At RCN Congress in Harrogate last week, Health Secretary William Waldegrave announced an 8 per cent increase in Project 2000 bursaries from September 1991 - an average increase of L320. PMID- 27662966 TI - Patti Sheeks. AB - Dear Patti, I am a first-year nursing student, and l want to transfer my training to another part of the UK. My girlfriend is moving because of her job and I want to go with her. PMID- 27662968 TI - Just imagine. PMID- 27662967 TI - The missing link. AB - How effectively do hospital nurses share patient information with their professional colleagues who work in the outside community? PMID- 27662969 TI - Tradimus MUG SHOTS. PMID- 27662971 TI - Working through the cuts. AB - It is still hard for many of us to imagine how it might feel to be suddenly told you are redundant. It is an impersonal word that falls harshly on the ear: meaning surplus to requirements, it suggests an insignificant loss. PMID- 27662970 TI - Association between the neutrophil-to-lymphocyte ratio, a new marker of systemic inflammation, and restless legs syndrome. AB - INTRODUCTION: Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is characterised by abnormal sensations in the legs as well as dysaesthesia. Although the aetiology of RLS has not yet been determined, it may be associated with systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) is a new and simple marker indicating systemic inflammation. The present study aimed to investigate the relationship between systemic inflammation and RLS through the use of the NLR. METHODS: A total of 75 newly diagnosed patients with RLS and 56 healthy control subjects were included in the study. Baseline NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The NLRs of the two groups were compared. RESULTS: There were no significant differences in gender and age between the two groups. The NLR was 1.96 +/- 0.66 in the patient group and 1.67 +/- 0.68 in the control group (p = 0.005). Receiver operating characteristic analysis was performed to determine the cut-off value of NLR to predict RLS. The NLR was predictive at 1.58 with a 64% sensitivity and 50% specificity (95% confidence interval 0.55-0.74, area under curve 0.648 +/- 0.05). The NLR was found to be statistically higher in patients with RLS and may be used to predict RLS. CONCLUSION: The aetiology of RLS remains undetermined. The present study showed that systemic inflammation may play a role in RLS. However, RLS could also be associated with systemic inflammatory diseases. This relationship is supported by high NLR values, which are related to chronic systemic inflammation. PMID- 27662972 TI - Nursing world mourns Robert Tiffany. AB - The nursing profession is mourning the loss of Robert Tiffany OBE, Director of Patient Services and Chief Nursing Officer at The Royal Marsden Hospital, who died in hospital last week, aged 50. PMID- 27662973 TI - Nurses must speak plainer language. AB - Nurses are the main source of information to patients' families but must learn to use language next of kin can understand, a 'Quality Roadshow' conference heard last week. PMID- 27662974 TI - Nurse to check patients are eating well. AB - A trained nurse should be chosen on every ward to make sure patients are eating well in hospital, new nutritional guidelines recommend. PMID- 27662976 TI - Fawcett-Henesy joins health strategy taskforce. AB - Ainna Fawcett-Henesy, Director of Nursing at SE Thames Regional Health Authority, is to be nursing's representative on the task force implementing the government's health strategy for London. PMID- 27662975 TI - RHAs to be retained but will be slimmed down. AB - Regional nurses have welcomed Health Secretary Virginia Bottomley's plans to retain England's 14 regional health authorities, although the slimmed-down regional health authorities will see their workforces cut by more than half. PMID- 27662977 TI - Call to end nursing subservience. AB - The RCN is calling for amendments to the Mental Health Act to end what it calls 'nursing's subservience to psychiatry'. PMID- 27662978 TI - Nurses work. AB - *Four senior nurses are the first to face compulsory redundancy in Scotland, after the North Ayrshire Unit announced they were no longer needed. PMID- 27662980 TI - 'Sell your cost-effectiveness'. AB - Nurses must now grab pivotal roles in the shift towards primary care by selling the cost-effectiveness of their health promotion and prevention work, RCN General Secretary Christine Hancock declared. PMID- 27662979 TI - Student whistleblowers out in the cold. AB - The UKCC's recently published student guidelines are a 'major disappointment' as they fail to support placement whistleblowers, the RCN Association of Nursing Students conference heard last week. PMID- 27662981 TI - Mental illness for up to 50 per cent of homeless people. AB - As many as half of all homeless people in Britain suffer from significant mental illness, a new study has revealed. PMID- 27662982 TI - Irish nurse killed in Somalia. AB - The murder of Irish nurse Valerie Place, pictured in Baidoa just two hours before she was shot by Somalian gunmen last week, has forced aid workers to take steps to protect themselves in the war- tom East African republic. Valerie, who had been in Somalia since finishing her nurse training at St James Hospital in Dublin last September, worked for the Irish humanitarian organisation Concern, which has 22 other nurses working in the country. Ms Place died when her car came under attack on the road outside Mogadishu. Jack Finucane, Head of Concern's Africa Division, said volunteers would no longer travel by road in Somalia. Nula Corcoran, Principal Tutor at St James Hospital in Dublin, said Valerie was a 'lovely person, with excellent potential'. PMID- 27662984 TI - A need to be 'indispensable'. AB - Nurses must lead some of the innovations occurring in the health service and make their services indispensable to managers, a leading member of the NHS Management Executive said last week. Sarah Waller, head of the NHSME Personnel Development Division, told a conference at St George's. PMID- 27662985 TI - Paediatric nurse shortage contributes to accident rates. AB - Shortages of qualified paediatric nurses contribute to the number of accidents on children's wards, a Royal College of Nursing Adviser in Nursing Practice claimed last week. PMID- 27662986 TI - Tribute for Scotland's NHS Chief Executive. AB - A nurses' leader has paid tribute to the work of Scotland's first NHS Chief Executive, Don Cruickshank, whose appointment as Director General of Telecommunications was announced by Michael Heseltine, President of the Board of Trade last week. Mr Cruikshank, who will take up his new post on April 1, 'always maintained a lively interest in nursing issues,' RCN Scottish Board Secretary June Andrew's told Nursing Standard last week. PMID- 27662987 TI - New network to relieve feeling of isolation. AB - Feelings of isolation among nurses involved in practice development could be curbed with the launch of a new information network. Set up by the King's Fund Centre in response to nurses' demands, the Nursing Development Network is open to any individuals and units wanting to share information or learn from others, said project worker, Pippa Gough at the London launch. PMID- 27662988 TI - Parliament. AB - Whitehall has been forced to admit the existence of a previously undeclared NHS 'intelligence' unit now suspected of providing political advice to ministers. PMID- 27662991 TI - Disabled children more at risk of abuse. AB - Disabled children are at extra risk of sexual and physical abuse, hard-hitting new research suggests. PMID- 27662990 TI - Reluctance over reporting malpractice. AB - Health service staff have become more reluctant to speak to the media about malpractice since the introduction of market reforms, a survey by health union MSF reveals. PMID- 27662992 TI - ? AB - Loud appeal: Former England cricket captain David Gower is to become patron of the The Macmillion Mile Challenge' in aid of the Macmillan Nurse Appeal, which so far has raised L20 million to fund 260 cancer care nurses. From May 8 to 16, people all over the country will be invited to cover a mile, and donate L1 to the Appeal for each one covered. A similar event last year raised L423,000. David is pictured recruiting participants on the pitch in Calcutta during England's recent Indian tour. PMID- 27662993 TI - CNs must support Primary Health Care Charter. AB - Chief Nursing Officer Yvonne Moores has called for community nurses to participate in drawing up a Primary Health Care Charter in their workplaces. Speaking at a satellite teleconference staged last week, Mrs Moores told 2,000 community nurses, health visitors and GPs linked up in centres around the country they must encourage and support the Primary Care Charter. PMID- 27662994 TI - Seen to be above suspicion. AB - Nurses must be completely above suspicion in their dealings with commercial sponsors and drug firms, according to new NHS Management Executive guidelines. Nurses should refuse to accept gifts, turn down hospitality they can not return and declare any connection with an outside business which may be seen as clouding their professional judgement, the advice says. Responsibility applies to all NHS staff, from those who commit resources directly, such as by ordering goods, to those involved in discharging patients to residential facilities who may have an interest in a private nursing home. The guidelines seem set to become increasingly important to nurses, as more take up purchasing positions, some have their posts sponsored, and the profession awaits the go-ahead for nurse prescribing. The new NHSME advice updates earlier guidelines and puts flesh on the bones of the UKCC Code of Professional Conduct. PMID- 27662995 TI - Aggression Farrell GA and Gray C Scutari Press 158pp L14.99 1-87 1364 60 4 [Formula: see text]. AB - In Aggression: A Nurse's Guide to Therapeutic Management we have a concise, intelligent account of the theory of aggressive incidents and what to do about them when they occur. The book is designed to improve nurses' knowledge base, self-understanding and to offer pointers for action in a practical setting; it achieves the aim admirably. The use of Eric Berne's theory of transactional analysis (TA) highlights personality traits of both client and nurse, and suggestions are put forward as to how TA may be used to aid social interactions. Aggression is well-argued, logical and straightforward and, above all, is an example of applying theory to practice. PMID- 27662996 TI - The Abuse of the Briefly J Pritchard The Abuse of the Briefly jessica kinsley 174pp L16.95 1-85302-122-9 [Formula: see text]. AB - J'ackie Pritchard's The Abuse of the Elderly is a brief overview of some of the literature on the topic and provides workshop materials which may be used by trainers/teachers to explore some of the many issues involved. Given the emphasis on utilising people with different skills within a team to undertake health and social care, those who come in contact with older people must be aware of the need to prevent, detect and deal with elder abuse. This book may be helpful to those responsible for delegating aspects of care to others and raise their awareness to the possibilities of meeting it and also in the development of guidelines as to any action to be taken. PMID- 27662997 TI - Assessing interventions, volume 4 Assessing interventions, volume 4 Tudiver F et al SAGE pubilcation 246pp L14.50 0-8039-477-2 [Formula: see text]. AB - Of the 26 contributors to Assessing Interventions: Traditional and Innovative Methods, Volume 4, there is only one nursing contributor; the majority of the remainder being medical doctors from the USA. Of the 246 pages, just nine are used by the nurse contributor, who says little that is new about qualitative methods in researching nursing care. The book needs to be read with the primary health-care team in mind.. It is divided into four sections. Section One considers basic issues in assessing interventions in primary care; the second section looks at the application of alternative methodologies - quantitative and qualitative. The third section explores specific topics and gives practical examples of how research was conducted by the authors and others within their disciplines. Section Four presents a panel discussion and considers future developments in primary care research. It will be of interest to anyone who may be presently involved in the evaluation of patient-centred research. The analysis and evaluation throughout the chapters, particularly in the third section, are worth having as an addendum to other research texts. Assessing Interventions will be of some value to lecturers in nursing, though perhaps not as a main text, but its price makes it accessible. PMID- 27662999 TI - Effective interaction with patients A Faulkner Effective interaction with patients Churchill Livingstone 110pp L8.95 0-443-04226-8 [Formula: see text]. AB - One of a series for students undertaking Project 2000 courses, Effective Interaction with Patients, as an initial text, encourages readers to consider many key aspects of communicating with patients and promotes the idea that skilled communication is an essential part of effective nursing Ann Faulkner deliberately chooses not to discuss theories of effective communication. but draws on her considerable experience to provide examples from clinical practice to illustrate specific points and demonstrate effective and ineffective types of communication. A list of further reading is provided at the end of book, but references within the text are sparse. Since there is a growing body of research in communication which could have been cited, this lack is disappointing. Many nurses are unfamiliar with recent research related to communication; they are unlikely to recognise the use made of it, which is embedded in this book. The sparse referencing and deceptively easy- to-read style could lead students and teachers to dismiss the book as unsuitable for a Project 2000 style of education. This would be a pity, as the style of communication described and advocated within is one which I believe most patients would welcome receiving in practice. PMID- 27663000 TI - Health care research by degrees N Reid Health care research by degrees Blackwell Scientific 162pp L13.99 0632-03466-1 [Formula: see text]. AB - Inadequately understood statistics so often cloud both the argument of the researcher and the judgement of the reader. Norma Reid brings a refreshing clarity to a complex topic; she takes the mystification and mystique out of statistics. Her basic premiss that theory ought to be based on practical utility and relevance shines through her text and helps to make the subject accessible co clinicians who want to understand the underpinnings of their practice. Research methods, particularly qualitative approaches, are sketchily dealt with when compared with the wealth of detail on the mechanics of computing. Also, it is awkward to find methods and analysis not clearly separated in places (eg, Delphi studies), but ample references direct the reader to more expansive sources. Any attempt to steer the uninitiated through the minefields of computing is fraught with difficulties, and some will be disappointed to find one system used exclusively, but, perhaps, it serves as an illustration rather than a course to be slavishly followed. PMID- 27663001 TI - Community care J Bornat et al Community care Macmillan 346pp L10.99 0-333-58715-4 [Formula: see text]. AB - With the implementation of the 'Caring tor People' section of the NHS and Community Care Act in April 1993, the publication of this latest addition to Open University's library is timely. Community Care: A Reader is produced as a set book tor OU's Diploma in Health and Social Welfare. Its merits include: its strong focus on the role of informal carers and voluntary organisations; the analysis of a wide range of research; the examination of the challenges facing carers from ethnic minorities; and the assessment of the development of mutual health care. The book's weakness is highlighted in its lack of analysis of the general health issues in securing and developing community care. PMID- 27663002 TI - The trouble with medicine M Konner The trouble with medicine BBC Books 208pp L16.99 0-563-36377-0 [Formula: see text]. AB - To accompany the BBC television series of the same name, The Trouble with Medicine explores the doctor/ patient relationship, hospital medicine, drugs, genetic medicine, surgery, mental disorder, life-support and HIV/AIDS. Dr Melvin Konner draws on material from the UK, the USA, Austria, Australia, India, and Spain to illustrate the development of each chapter's subject, to compare different health-care systems, and to raise related ethical issues. It is the priorities implicit in Western medical practice which he brings into question - particularly the prestige of high-tech acute care which burns up resources perhaps better placed in preventive services. PMID- 27663005 TI - Watson's medical-surgical nursing J Royle and M Walsh Watson's medical-surgical nursing BailliereTindall 1038pp L15.95 0 7020-1515-6 [Formula: see text]. AB - The fourth edition of Watson's was written to support students in a time when nursing is experiencing great change. The previous editions, extensively referenced by both learners and qualified ' nurses, became a regular feature of many wards and departments. PMID- 27663004 TI - Nurse training for mothers Nurse training for mothers M Bond 52pp L3.45 0964-7902 [Formula: see text]. AB - Meg Bond's Nurse Training for Mothers is part of a wider Department of Health funded research survey into the labour market. She concentrates on the availability of part-time RGN courses for mothers. It makes depressing reading and illustrates, like a fly set in amber, earlier worries about the demographic crisis. PMID- 27663006 TI - Support worker gaining T Chandler Support worker gaining Bailliere Tindall 146pp L7.50 0-7020-1562.8 [Formula: see text]. AB - Support Worker Training: A Guide for Health Professionalsi s about the training of that new helper - the health care assistant (HCA), or health care support worker (HCSW). The novice is guided through the web of information surrounding the history of Project 2000 and the conception of the support-worker role. PMID- 27663008 TI - Levels of skill in nursing homes. AB - There is no relationship between B McCarthy failing to get a job in the NHS and the level of skill of nursing home nurses ('Refreshing attitude a succinct success', Letters, February 17). It is true we rarely use advanced mechanical or electronic gadgetry, but is that nursing? A nurse can recognise patterns on a cardiac monitor - but a pigeon can differentiate stimuli on an oscillascope. PMID- 27663009 TI - Perfect tuning for work campaign. AB - The Nurses work campaign could not have been better timed as far as I am concerned: I became unemployed a few weeks ago. Having qualified in 1988, I accepted a job in the theatre recovery suite and began to formulate plans for the future. I set my sights on a career in district nursing and was advised to seek a transfer to any general ward, medical or surgical, for management experience. PMID- 27663010 TI - ? AB - How dare B McCarthy imply that being 'forced' to work in a nursing home is not a 'real job' for a nurse and leads to being 'deskilled', whatever that means? I agree that each field of nursing requires different skills, but there must also be a basic core of skills for each field in which one chooses to work, wherever that may be. PMID- 27663011 TI - Acknowledging the retired contribution. AB - In this European Year of Older People and Solidarity Between Generations, should not there be some acknowledgement of those retired ward sisters who battled to keep their teams together and run their wards against all odds, almost unaware of what was about to hit the NHS. PMID- 27663012 TI - ? AB - "There aren't any nurses, you have to get one of these the hospital library". PMID- 27663013 TI - The NHS has its limitations. AB - Virginia Bottomley's announcement about the closure of some London hospitals illustrates the effect of the internal market system in the NHS. PMID- 27663015 TI - The risk of caring too much? AB - Until last week I was employed as an RGN in a private nursing home. I attempted to act as patient advocate when questioning the use of certain topical applications to pressure areas and superficial sores. PMID- 27663014 TI - Improving one's knowledge of ME. AB - Having suffered from myalgic encephalomyelitis (ME) for some time, I remain concerned about the ignorance of medical and nursing staff regarding this illness. PMID- 27663016 TI - ? AB - We welcome all readers' letters, hut reserve the right to edit them and to withhold names and addresses - either to protect readers or the journal, or both. PMID- 27663017 TI - Fully involving staff in assessments. AB - I would refer Jan Fraser ('A kick up the assessment', Tradimus, February 17) to Doris Dunn's various writings on an assessment strategy for clinical practice. PMID- 27663018 TI - O'Grady-peyton international. AB - O'GRADY-PEYTON INTERNATIONAL which has been established since 1981 is one of the leading international recruitment agencies operating in the UK and Ireland. Each year it recruits close to 400 nurses, physiotherapists, occupational therapists and doctors for hospitals throughout the United States, Middle East and Germany. PMID- 27663019 TI - Career listings. PMID- 27663020 TI - Experiences of adults with high-care needs and their family members with housing and support pathways in Australia. AB - PURPOSE: Many adults aged less than 65 years with high-care needs resulting from acquired disabilities are unable to access age-appropriate housing and support, and reside in residential aged care or live with family members who may struggle to navigate the disability support system. This qualitative study aimed to investigate the experiences of adults with high-care needs and their family members regarding pathways related to housing and support. METHOD: Two in-depth semi-structured interviews were conducted six months apart with 21 people aged 18 to 65 with high-care needs of varying etiology and living in different housing settings. Nineteen family members involved in decision-making about housing and supports were also interviewed. RESULTS: Thematic data analysis yielded five themes: (1) Traveling in different directions; (2) "the fight, the battle and the war"; (3) willing but wanting; (4) uncertainty and vulnerability; and (5) redefining social roles and relationships. CONCLUSIONS: Current disability policy is not satisfying the housing and support requirements of adults with high-care needs and their families. The findings provide rigorous, empirical evidence which indicate the urgent need to improve access to affordable, individualized housing and support packages, including financial, practical and informational support for family members involved in caring roles. Implications for Rehabilitation Individual preferences are an important consideration in housing and support arrangements for younger people with high-care needs alongside needs-based solutions. Individualized funding approaches may provide flexibility of care and choice in housing and support for people with disability. Family members willingly provide substantial informal care, support and advocacy for younger people with high needs but perceive their role as a constant "battle". Payment of family members in recognition of caring work was perceived as a solution to relieve family hardship and ensure optimal care. PMID- 27663022 TI - Marine genomics: insights and challenges. PMID- 27663021 TI - Structural integrity between executive control and reward regions of the brain predicts body fat percentage in chronic dieters. AB - Failure to maintain a healthy body weight may reflect a long-term imbalance between the executive control and reward systems of the brain. The current study examined whether the anatomical connectivity between these two systems predicted individual variability in achieving a healthy body weight, particularly in chronic dieters. Thirty-six female chronic dieters completed a food-cue reactivity task in the scanner. Two regions-of-interest (ROIs) were defined from the reactivity task: the inferior frontal gyrus (IFG), which engages cognitive control and the orbitofrontal cortex (OFC), which represents reward value. A white matter tract connecting these two ROIs was identified across participants using diffusion tensor imaging (DTI) and probabilistic tractography. Results showed a negative relationship between body fat percentage and white matter integrity within the identified tract. This suggests that reduced structural integrity between the OFC and IFG may be related to self-regulatory problems for those who chronically diet to control body weight. PMID- 27663023 TI - Innovative Use of Palladium Compounds To Selectively Detect Live Enterobacteriaceae in Milk by PCR. AB - Ethidium monoazide and propidium monoazide (EMA and PMA) have been used in combination with PCR for more than a decade to facilitate the discrimination of live and dead bacteria (LD discrimination). These methods, however, require many laborious procedures, including the use of a darkroom. Here, we demonstrate an innovative use of palladium compounds involving lower limits of detection and quantification of targeted live cells, fewer laborious procedures, lower costs, and potentially higher-throughput analysis than the use of EMA and PMA. We have also recently reported platinum compounds for LD discrimination, but platinum compounds carry costs that are 3 times higher because of the requirement for much larger amounts for LD discrimination than palladium compounds. Palladium compounds can penetrate dead (compromised) but not live bacteria and can be chelated primarily by chromosomal DNA and cell wall transmembrane proteins, with small amounts of DNA-binding proteins in vivo The new mechanism for palladium compounds is obviously different from that of platinum compounds, which primarily target DNA. Combining palladium compounds with PCR (Pd-PCR) in water resulted in discrimination between live and dead Enterobacteriaceae bacteria that was much clearer than that seen with the PMA method. Pd-PCR correlated with reference plating or with the currently used PMA-PCR method for pasteurized milk, based on EN ISO 16140:2003 validation. Pd-PCR enabled us to specifically detect and assay viable Enterobacteriaceae cells at concentrations of 5 to 10 CFU/ml in milk while following U.S./EU regulations after a 4.5-h process in a typical laboratory exposed to natural or electric light, as specified by U.S./EU regulations.IMPORTANCE Ethidium monoazide and propidium monoazide (EMA and PMA) facilitate the discrimination of live and dead bacteria (LD discrimination). These methods, however, require many laborious procedures, including the use of a darkroom. Here, we demonstrate an innovative use of palladium compounds involving fewer laborious procedures, lower costs, and potentially higher-throughput analysis than the use of EMA and PMA. We have also recently reported platinum compounds for LD discrimination, but platinum compounds carry costs that are 3 times higher because of the requirement for much larger amounts for LD discrimination than palladium compounds, which have also a novel reaction mechanism different from that of platinum compounds. In view of testing cost, palladium compounds are also very useful here compared with platinum compounds. Ultimately, the innovative Pd-PCR method may be also substituted for the currently used reference plating methods. PMID- 27663024 TI - A Clonal Lineage of Fusarium oxysporum Circulates in the Tap Water of Different French Hospitals. AB - : Fusarium oxysporum is typically a soilborne fungus but can also be found in aquatic environments. In hospitals, water distribution systems may be reservoirs for the fungi responsible for nosocomial infections. F. oxysporum was previously detected in the water distribution systems of five French hospitals. Sixty-eight isolates from water representative of all hospital units that were previously sampled and characterized by translation elongation factor 1alpha sequence typing were subjected to microsatellite analysis and full-length ribosomal intergenic spacer (IGS) sequence typing. All but three isolates shared common microsatellite loci and a common two-locus sequence type (ST). This ST has an international geographical distribution in both the water networks of hospitals and among clinical isolates. The ST dominant in water was not detected among 300 isolates of F. oxysporum that originated from surrounding soils. Further characterization of 15 isolates by vegetative compatibility testing allowed us to conclude that a clonal lineage of F. oxysporum circulates in the tap water of the different hospitals. IMPORTANCE: We demonstrated that a clonal lineage of Fusarium oxysporum inhabits the water distribution systems of several French hospitals. This clonal lineage, which appears to be particularly adapted to water networks, represents a potential risk for human infection and raises questions about its worldwide distribution. PMID- 27663025 TI - Crz1p Regulates pH Homeostasis in Candida glabrata by Altering Membrane Lipid Composition. AB - The asexual facultative aerobic haploid yeast Candida glabrata is widely used in the industrial production of various organic acids. To elucidate the physiological function of the C. glabrata transcription factor Crz1p (CgCrz1p) and its role in tolerance to acid stress, we deleted or overexpressed the corresponding gene, CgCRZ1 Deletion of CgCRZ1 resulted in a 60% decrease in the dry weight of cells (DCW) and a 50% drop in cell viability compared with those of the wild type at pH 2.0. Expression of lipid metabolism-associated genes was also significantly downregulated. Consequently, the proportion of C18:1 fatty acids, the ratio of unsaturated to saturated fatty acids, and the ergosterol content decreased by 30%, 46%, and 30%, respectively. Additionally, membrane integrity, fluidity, and H+-ATPase activity were reduced by 45%, 9%, and 50%, respectively. In contrast, overexpression of CgCrz1p increased C18:1 and ergosterol contents by 16% and 40%, respectively. Overexpression also enhanced membrane integrity, fluidity, and H+-ATPase activity by 31%, 6%, and 20%, respectively. Moreover, in the absence of pH buffering, the DCW and pyruvate titers increased by 48% and 60%, respectively, compared to that of the wild type. Together, these results suggest that CgCrz1p regulates tolerance to acidic conditions by altering membrane lipid composition in C. glabrataIMPORTANCE This study provides insight into the metabolism of Candida glabrata under acidic conditions, such as those encountered during the industrial production of organic acids. We found that overexpression of the transcription factor CgCrz1p improved viability, biomass, and pyruvate yields at a low pH. Analysis of plasma membrane lipid composition indicated that CgCrz1p might play an important role in its integrity and fluidity and that it enhanced the pumping of protons in acidic environments. We propose that altering the structure of the cell membrane may provide a successful strategy for increasing C. glabrata productivity at a low pH. PMID- 27663026 TI - Response of germ-free mice to colonization with O. formigenes and altered Schaedler flora. AB - : Colonization with Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host/O.formigenes and microbe/O.formigenes interactions, germ-free or altered Schaedler flora (ASF) mice were colonized with O.formigenes Germ-free mice were stably colonized with O.formigenes suggesting O.formigenes does not require other organisms to sustain its survival. Examination of intestinal material indicated no viable O.formigenes in the small intestine, ~4 * 106 O.formigenes per 100mg contents in the cecum and proximal colon, and ~0.02% of total cecal O. formigenes cells were tightly associated to the mucosa. O.formigenes did not alter the overall microbial composition of ASF, and ASF did not impact O.formigenes capacity to degrade dietary oxalate in the cecum. 24-hour urine and fecal collections within metabolic cages in semi-rigid isolators demonstrated that introduction of ASF into germ-free mice significantly reduced urinary oxalate excretion. These experiments also showed that mono-colonized O.formigenes mice excrete significantly more urinary calcium compared to germ-free mice, which may be due to degradation of calcium oxalate crystals by O.formigenes and the subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of defined-flora O.formigenes mouse models should improve our understanding of O.formigenes host and microbe interactions. These data support the use of O.formigenes as a probiotic that has limited impact on the composition of the resident microbiota but providing efficient oxalate degrading function. IMPORTANCE: Despite evidence suggesting a lack of O. formigenes colonization is a risk factor for calcium oxalate stone formation, little is known about O. formigenes biology. This study is the first to utilize germ-free mice to examine the response to mono-colonization with O. formigenes and the impact of a defined bacterial cocktail, altered Schaedler flora, on O. formigenes colonization. This study demonstrates that germ-free mice on their regular diet remain mono colonized with O. formigenes, and suggests that further studies with O. formigenes gnotobiotic mouse models could improve our understanding of O. formigenes biology and host/O. formigenes and microbe/O. formigenes interactions. PMID- 27663027 TI - Adaptation of Akkermansia muciniphila to the Oxic-Anoxic Interface of the Mucus Layer. AB - Akkermansia muciniphila colonizes the mucus layer of the gastrointestinal tract, where the organism can be exposed to the oxygen that diffuses from epithelial cells. To understand how A. muciniphila is able to survive and grow at this oxic anoxic interface, its oxygen tolerance and response and reduction capacities were studied. A. muciniphila was found to be oxygen tolerant. On top of this, under aerated conditions, A. muciniphila showed significant oxygen reduction capacities and its growth rate and yield were increased compared to those seen under strict anaerobic conditions. Transcriptome analysis revealed an initial oxygen stress response upon exposure to oxygen. Thereafter, genes related to respiration were expressed, including those coding for the cytochrome bd complex, which can function as a terminal oxidase. The functionality of A. muciniphila cytochrome bd genes was proven by successfully complementing cytochrome-deficient Escherichia coli strain ECOM4. We conclude that A. muciniphila can use oxygen when it is present at nanomolar concentrations.IMPORTANCE This article explains how Akkermansia muciniphila, previously described as a strictly anaerobic bacterium, is able to tolerate and even benefit from low levels of oxygen. Interestingly, we measured growth enhancement of A. muciniphila and changes in metabolism as a result of the oxygen exposure. In this article, we discuss similarities and differences of this oxygen-responsive mechanism with respect to those of other intestinal anaerobic isolates. Taken together, we think that these are valuable data that indicate how anaerobic intestinal colonizing bacteria can exploit low levels of oxygen present in the mucus layer and that our results have direct relevance for applicability, as addition of low oxygen concentrations could benefit the in vitro growth of certain anaerobic organisms. PMID- 27663028 TI - Two Outer Membrane Proteins Contribute to Caulobacter crescentus Cellular Fitness by Preventing Intracellular S-Layer Protein Accumulation. AB - Surface layers, or S-layers, are two-dimensional protein arrays that form the outermost layer of many bacteria and archaea. They serve several functions, including physical protection of the cell from environmental threats. The high abundance of S-layer proteins necessitates a highly efficient export mechanism to transport the S-layer protein from the cytoplasm to the cell exterior. Caulobacter crescentus is unique in that it has two homologous, seemingly redundant outer membrane proteins, RsaFa and RsaFb, which together with other components form a type I protein translocation pathway for S-layer export. These proteins have homology to Escherichia coli TolC, the outer membrane channel of multidrug efflux pumps. Here we provide evidence that, unlike TolC, RsaFa and RsaFb are not involved in either the maintenance of membrane stability or the active export of antimicrobial compounds. Rather, RsaFa and RsaFb are required to prevent intracellular accumulation and aggregation of the S-layer protein RsaA; deletion of RsaFa and RsaFb led to a general growth defect and lowered cellular fitness. Using Western blotting, transmission electron microscopy, and transcriptome sequencing (RNA-seq), we show that loss of both RsaFa and RsaFb led to accumulation of insoluble RsaA in the cytoplasm, which in turn caused upregulation of a number of genes involved in protein misfolding and degradation pathways. These findings provide new insight into the requirement for RsaFa and RsaFb in cellular fitness and tolerance to antimicrobial agents and further our understanding of the S-layer export mechanism on both the transcriptional and translational levels in C. crescentusIMPORTANCE Decreased growth rate and reduced cell fitness are common side effects of protein production in overexpression systems. Inclusion bodies typically form inside the cell, largely due to a lack of sufficient export machinery to transport the overexpressed proteins to the extracellular environment. This phenomenon can conceivably also occur in natural systems. As one example of a system evolved to prevent intracellular protein accumulation, our study demonstrates that Caulobacter crescentus has two homologous outer membrane transporter proteins that are involved in S-layer export. This is an interesting case study that demonstrates how bacteria can evolve redundancy to ensure adequate protein export functionality and maintain high cellular fitness. Moreover, we provide evidence that these two outer membrane proteins, although being the closest C. crescentus homologs to TolC in E. coli, do not process TolC functionality in C. crescentus. PMID- 27663029 TI - Production and Characterization of Neutralizing Antibodies against Bungarus multicinctus Snake Venom. AB - The venom of the banded krait (Bungarus multicinctus), one of the major venomous species in Taiwan, contains neurotoxic venom proteins (B. multicinctus proteins) that pose a serious medical problem in tropical and subtropical countries. Even though horse-derived serum is an efficient therapy against snake venom, it is associated with a high cost and side effects. Therefore, developing a more cost effective alternative treatment option is highly envisaged. In this study, chickens were immunized with B. multicinctus proteins, and polyclonal immunoglobulin Y (IgY) antibodies were purified from eggs. IgY showed a binding activity to B. multicinctus proteins that was similar to horse antivenin, and its titer in chickens lasted for at least 6 months. We constructed two antibody libraries by phage display antibody technology, which contain 1.0 * 107 and 2.9 * 108 transformants, respectively. After biopanning, a phage-based enzyme-linked immunosorbent assay (ELISA) indicated that specific clones were enriched. Thirty randomly selected clones expressing monoclonal single-chain variable-fragment (scFv) antibodies were classified into four groups with a short linker and two with a long linker. These selected scFv antibodies showed specific binding activities to B. multicinctus proteins but not to the venomous proteins of other snakes. Most importantly, polyclonal IgY demonstrated a similar neutralization efficiency as did horse-derived antivenin in mice that were injected with a minimum lethal dosage (MLD) of venom proteins. A mixture of several monoclonal anti-B. multicinctus scFv antibodies was also able to partially inhibit the lethal effect on mice. We profoundly believe that IgY and scFv antibodies can be applied in developing diagnostic agents for wound exudates and as an alternative treatment for snakebite envenomation in the future.IMPORTANCE Snake envenomation is one of the global medical issues of concern. Horse-derived antivenin is an effective way to treat snakebites, but it is costly and occasionally causes severe side effects. In this study, we first generated and characterized IgY antibodies with neutralization activity in chickens. Subsequently, we generated a panel of monoclonal scFv antibodies using phage display antibody technology. A mixture of scFv antibodies was able to partially inhibit the lethal effect in mice that were injected with lethal dosages of venom proteins and prolong their survival time. We believe that chicken-derived IgY and scFv antibodies have great potential for the development of diagnostic agents for wound exudates and therapeutic agents against snake envenomation in the future. PMID- 27663030 TI - Novel Trifunctional Xylanolytic Enzyme Axy43A from Paenibacillus curdlanolyticus Strain B-6 Exhibiting Endo-Xylanase, beta-d-Xylosidase, and Arabinoxylan Arabinofuranohydrolase Activities. AB - The axy43A gene encoding the intracellular trifunctional xylanolytic enzyme from Paenibacillus curdlanolyticus B-6 was cloned and expressed in Escherichia coli Recombinant PcAxy43A consisting of a glycoside hydrolase family 43 and a family 6 carbohydrate-binding module exhibited endo-xylanase, beta-xylosidase, and arabinoxylan arabinofuranohydrolase activities. PcAxy43A hydrolyzed xylohexaose and birch wood xylan to release a series of xylooligosaccharides, indicating that PcAxy43A contained endo-xylanase activity. PcAxy43A exhibited beta-xylosidase activity toward a chromogenic substrate, p-nitrophenyl-beta-d-xylopyranoside, and xylobiose, while it preferred to hydrolyze long-chain xylooligosaccharides rather than xylobiose. In addition, surprisingly, PcAxy43A showed arabinoxylan arabinofuranohydrolase activity; that is, it released arabinose from both singly and doubly arabinosylated xylose, alpha-l-Araf-(1->2)-d-Xylp or alpha-l-Araf-(1 >3)-d-Xylp and alpha-l-Araf-(1->2)-[alpha-l-Araf-(1->3)]-beta-d-Xylp Moreover, the combination of PcAxy43A and P. curdlanolyticus B-6 endo-xylanase Xyn10C greatly improved the efficiency of xylose and arabinose production from the highly substituted rye arabinoxylan, suggesting that these two enzymes function synergistically to depolymerize arabinoxylan. Therefore, PcAxy43A has the potential for the saccharification of arabinoxylan into simple sugars for many applications. IMPORTANCE In this study, the glycoside hydrolase 43 (GH43) intracellular multifunctional endo-xylanase, beta-xylosidase, and arabinoxylan arabinofuranohydrolase (AXH) from P. curdlanolyticus B-6 were characterized. Interestingly, PcAxy43A AXH showed a new property that acted on both the C(O)-2 and C(O)-3 positions of xylose residues doubly substituted with arabinosyl, which usually obstruct the action of xylanolytic enzymes. Furthermore, the studies here show interesting properties for the processing of xylans from cereal grains, particularly rye arabinoxylan, and show a novel relationship between PcAxy43A and endo-xylanase Xyn10C from strain B-6, providing novel metabolic potential for processing arabinoxylans into xylose and arabinose. PMID- 27663031 TI - Functions and Unique Diversity of Genes and Microorganisms Involved in Arsenite Oxidation from the Tailings of a Realgar Mine. AB - : The tailings of the Shimen realgar mine have unique geochemical features. Arsenite oxidation is one of the major biogeochemical processes that occurs in the tailings. However, little is known about the functional and molecular aspects of the microbial community involved in arsenite oxidation. Here, we fully explored the functional and molecular features of the microbial communities from the tailings of the Shimen realgar mine. We collected six samples of tailings from sites A, B, C, D, E, and F. Microcosm assays indicated that all of the six sites contain both chemoautotrophic and heterotrophic arsenite-oxidizing microorganisms; their activities differed considerably from each other. The microbial arsenite-oxidizing activities show a positive correlation with soluble arsenic concentrations. The microbial communities of the six sites contain 40 phyla of bacteria and 2 phyla of archaea that show extremely high diversity. Soluble arsenic, sulfate, pH, and total organic carbon (TOC) are the key environmental factors that shape the microbial communities. We further identified 114 unique arsenite oxidase genes from the samples; all of them code for new or new-type arsenite oxidases. We also isolated 10 novel arsenite oxidizers from the samples, of which 4 are chemoautotrophic and 6 are heterotrophic. These data highlight the unique diversities of the arsenite-oxidizing microorganisms and their oxidase genes from the tailings of the Shimen realgar mine. To the best of our knowledge, this is the first report describing the functional and molecular features of microbial communities from the tailings of a realgar mine. IMPORTANCE: This study focused on the functional and molecular characterizations of microbial communities from the tailings of the Shimen realgar mine. We fully explored, for the first time, the arsenite-oxidizing activities and the functional gene diversities of microorganisms from the tailings, as well as the correlation of the microbial activities/diversities with environmental factors. The findings of this study help us to better understand the diversities of the arsenite-oxidizing bacteria and the geochemical cycle of arsenic in the tailings of the Shimen realgar mine and gain insights into the microbial mechanisms by which the secondary minerals of the tailings were formed. This work also offers a set of unique arsenite-oxidizing bacteria for basic research of the molecular regulation of arsenite oxidation in bacterial cells and for the environmentally friendly bioremediation of arsenic-contaminated groundwater. PMID- 27663032 TI - Clinics in diagnostic imaging (170). AB - A 30-year-old woman presented with a six-month history of left posterior heel pain. Physical examination revealed a tender, inflamed and indurated posterior heel with a visible bony prominence of the posterosuperior aspect of the calcaneus. Lateral ankle radiography showed a prominent left posterosuperior calcaneal tuberosity and thickening of the distal Achilles tendon outline. Magnetic resonance imaging demonstrated high-signal inflammatory fluid in the retrocalcaneal bursa, increased signal intensity and thickening of the Achilles tendon, and prominence of the posterior calcaneus tuberosity with reactive marrow oedema. The findings are consistent with Haglund's deformity. The patient underwent hind foot surgery after failing a six-month course of conservative therapy. There was no further recurrence of symptoms after surgery. The clinical and radiological features of Haglund's deformity are described, including a short discussion of other causes of hind foot pain. PMID- 27663033 TI - A rare presentation of histologically proven sarcoidosis of the knee: A case report and brief review of the literature. AB - We here report a patient with histologically proven sarcoidosis of the knee, a rare localization of sarcoidosis, which usually presents itself as a pulmonary disease. Case reports of radiological images that suggest osseous sarcoidosis of the appendicular skeleton are not so rare, however few are histologically proven. Since in our patient MRI could not distinguish between sarcoidosis and another (possibly malignant) disease, histological proof was obtained through a CT-guided biopsy. Imaging and treatment guidelines for extrapulmonary sarcoidosis are inexistent, due to lack of randomized trials. PMID- 27663035 TI - A Comparison of the Outcomes for Cartilage Defects of the Knee Treated With Biologic Resurfacing Versus Focal Metallic Implants. AB - PURPOSE: To compare the results of focal metallic resurfacing with biologic procedures in patients more than 35 years of age with isolated, full thickness defects of the femoral condyle. METHODS: A total of 61 patients met the selection criteria resulting in 30 patients treated with biological procedures, including debridement, microfracture, osteochondral autograft transplantation, osteochondral allograft, and autologous chondrocyte implantation (BIO group), and 32 patients treated with focal metallic resurfacing (CAP group). The BIO and CAP groups were matched according to treatment location, defect grade and size, and age profile. Outcomes included Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short Form-12, and satisfaction. The primary combination endpoint was determined as a 20% improvement (minimum clinically important difference-20) on WOMAC pain and function at 2 years and no additional index lesion-related surgical intervention. Safety and effectiveness were also reported. RESULTS: Thirty patients in the BIO group (mean age of 44.6, range 35-64) had an average follow-up of 2.6 years and 32 patients in the CAP group (mean age 47.9, range 37 68) were followed for 2.0 years. Fifty-three percent in the BIO group and 75% in the CAP group achieved success per the endpoint definition. The mean total WOMAC score improved significantly for both groups (BIO: 57-78; P < .001) (CAP: 41-86; P < .001). The physical component score (Short Form-12 PCS) improved significantly in the CAP group only (30-36.4; P < .001). Good to excellent patient satisfaction was achieved by 80% in BIO and 91% in CAP. There were 4 secondary procedures on the index lesion in the BIO group and 2 in the CAP group. CONCLUSIONS: Careful patient selection can achieve high satisfaction rates with both biological and focal metal resurfacing procedures for the treatment of isolated focal chondral lesions of the femoral condyle in the knee. Focal metallic resurfacing results in similar clinical outcomes and provides excellent success rates at short-term follow-up. LEVEL OF EVIDENCE: Level III comparative study. PMID- 27663034 TI - In Vivo Anterolateral Ligament Length Change in the Healthy Knee During Functional Activities-A Combined Magnetic Resonance and Dual Fluoroscopic Imaging Analysis. AB - PURPOSE: To measure the in vivo anterolateral ligament (ALL) length change in healthy knees during step-up and sit-to-stand motions. METHODS: Eighteen healthy knees were imaged using magnetic resonance and dual fluoroscopic imaging techniques during a step-up and sit-to-stand motion. The ALL length change was measured using the shortest three-dimensional wrapping path, with its femoral attachment located slightly anterior-distal (ALL-Claes) or posterior-proximal (ALL-Kennedy) to the fibular collateral ligament attachment. The ALL length measured from the extended knee position of the non-weight-bearing magnetic resonance scan was used as a reference to normalize the length change. RESULTS: During the step-up motion (approximately 55 degrees flexion to full extension), both the ALL-Claes and ALL-Kennedy showed a significant decrease in length of 21.2% (95% confidence interval 18.0-24.4, P < .001) and 24.3% (20.6-28.1, P < .001), respectively. During the sit-to-stand motion (approximately 90 degrees flexion to full extension), both the ALL-Claes and ALL-Kennedy showed a consistent, significant decrease in length of 35.2% (28.8-42.2, P < .001) and 39.2% (32.4-46.0, P < .001), respectively. From approximately 90 degrees to 70 degrees of flexion, a decrease in length of approximately 6% was seen; 70 degrees of flexion to full extension resulted in an approximately 30% decrease in length. CONCLUSIONS: The ALL was found to be a nonisometric structure during the step-up and sit-to-stand motion. The length of the ALL was approximately 35% longer at approximately 90 degrees of knee flexion when compared with full extension and showed decreasing length at lower flexion angles. Similar ALL length change patterns were found with its femoral attachment located slightly anterior-distal or posterior-proximal to the fibular collateral ligament attachment. CLINICAL RELEVANCE: These data suggest that, if performing anatomic ALL reconstruction, graft fixation may be performed beyond 70 degrees flexion to reduce the chance of lateral compartment overconstraint. Anatomic ALL reconstruction may affect the knee kinematics more in high flexion than at low flexion angles. PMID- 27663036 TI - James Walter (Walt) Simmons Jr. PMID- 27663037 TI - Scaling Hemodialysis Target Dose to Reflect Body Surface Area, Metabolic Activity, and Protein Catabolic Rate: A Prospective, Cross-sectional Study. AB - BACKGROUND: Women and small men treated by hemodialysis (HD) have reduced survival. This may be due to use of total-body water (V) as the normalizing factor for dialysis dosing. In this study, we explored the equivalent dialysis dose that would be delivered using alternative scaling parameters matching the current recommended minimum Kt/V target of 1.2. STUDY DESIGN: Prospective cross sectional study. SETTING & PARTICIPANTS: 1,500 HD patients on a thrice-weekly schedule, recruited across 5 different centers. PREDICTORS: Age, sex, weight, race/ethnicity, comorbid condition level, and employment status. OUTCOMES: Kt was estimated by multiplying V by 1.2. Kt/body surface area (BSA), Kt/resting energy expenditure (REE), Kt/total energy expenditure (TEE) and Kt/normalized protein catabolic rate (nPCR) equivalent to a target Kt/V of 1.2 were then estimated by dividing Kt by the respective parameters. MEASUREMENTS: Anthropometry, HD adequacy details, and BSA were obtained by standard procedures. REE was estimated using a novel validated equation. TEE was calculated from physical activity data obtained using the Recent Physical Activity Questionnaire. nPCR was estimated using a standard formula. RESULTS: Mean BSA was 1.87m2; mean REE, 1,545kcal/d; mean TEE, 1,841kcal/d; and mean nPCR, 1.03g/kg/d. For Kt/V of 1.2, there was a wide range of equivalent doses expressed as Kt/BSA, Kt/REE, Kt/TEE, and Kt/nPCR. The mean equivalent dose was lower in women for all 4 parameters (P<0.001). Small men would also receive lower doses compared with larger men. Younger patients, those with low comorbidity, those employed, and those of South Asian race/ethnicity would receive significantly lower dialysis doses with current practice. LIMITATIONS: Cross-sectional study; physical activity data collected by an activity questionnaire. CONCLUSIONS: Current dosing practices may risk underdialysis in women, men of smaller body size, and specific subgroups of patients. Using BSA-, REE-, or TEE-based dialysis prescription would result in higher dose delivery in these patients. PMID- 27663038 TI - The US Renal Data System "Pie Chart of Death". PMID- 27663040 TI - Membranous Lupus Nephritis: The Same, But Different. AB - Membranous lupus nephritis (MLN) has a favorable prognosis compared to proliferative lupus nephritis (PLN) or combined MLN/PLN, although a significant proportion of cases will progress to end-stage kidney disease. There is considerable morbidity associated with thrombotic complications and treatment. Nondirected care includes renin-angiotensin-aldosterone system blockade, cardiovascular risk management, and antimalarial agents. There may be a role for corticosteroid monotherapy in some patients, but this requires further investigation. Clinical trials and observational reports have led to different immunosuppression regimens for MLN, although high-grade evidence favoring a particular agent remains elusive. Established medications used in the treatment of PLN, such as mycophenolate, cyclophosphamide, and azathioprine, may also be efficacious in MLN, or at least steroid sparing. The calcineurin inhibitors appear promising as an alternative treatment in MLN, particularly with emerging experimental data supporting their nonimmunologic antiproteinuric effects. There is also emerging evidence for "multitargeted therapy" in combined MLN/PLN, although the long-term efficacy is still unproved. PMID- 27663039 TI - Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial. AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people worldwide. Vasopressin promotes disease progression. STUDY DESIGN: A randomized controlled trial with equal (1:1) allocation. SETTING & PARTICIPANTS: This trial examined the effect of combining a low-osmolar (low-sodium [1,500mg/d], low-protein [0.8g per kilogram of body weight]) diet and adjusted water intake on vasopressin secretion in 34 patients with ADPKD. INTERVENTION: Participants were randomly assigned to receive a low-osmolar diet followed by adjusted water intake to achieve urine osmolality <= 280mOsm/kg water versus no intervention for 2 weeks. OUTCOME: The primary outcome of the study was change (delta) in copeptin levels and urine osmolality between the intervention and control groups from baseline to 2 weeks. MEASUREMENTS: Fasting plasma copeptin level, 24-hour urine osmolality, and total solute intake. RESULTS: Baseline characteristics of the 2 groups were similar. Mean plasma copeptin levels and urine osmolality declined from 6.2+/-3.05 (SD) to 5.3+/-2.5pmol/L (P=0.02) and from 426+/-193 to 258+/-117mOsm/kg water (P=0.01), respectively, in the intervention group compared to a nonsignificant change in the control group (from 4.7+/-3.6 to 5.07+/-4pmol/L [P=0.2] and 329+/-159 to 349+/-139mOsm/kg water [P=0.3], respectively). The change in copeptin levels (primary outcome) and urine osmolality was statistically significant between the intervention and control groups (delta copeptin, -0.86+/-1.3 vs +0.39+/-1.2pmol/L [P=0.009]; delta urine osmolality, -167+/-264 vs +20+/-80mOsm/kg water [P=0.007], respectively). Total urinary solute decreased in only the intervention group and significantly differed between groups at week 1 (P=0.03), reducing mean water prescription from 3.2 to 2.6L/d. LIMITATIONS: Small sample size and short follow-up. CONCLUSIONS: We developed a stepwise dietary intervention that led to a significant reduction in vasopressin secretion in patients with ADPKD. Furthermore, this intervention led to a reduction in water required for vasopressin reduction. PMID- 27663041 TI - Magnetic Resonance Imaging Assessment of Kidney Oxygenation and Perfusion During Sickle Cell Vaso-occlusive Crises. AB - BACKGROUND: Our understanding of the pathophysiologic processes underlying sickle cell nephropathy remains incomplete. We performed a pilot study to investigate the potential value of magnetic resonance imaging (MRI) for the assessment of kidney oxygenation and detection of potential changes to tissue perfusion and cellular integrity during a vaso-occlusive crisis. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: 10 homozygous patients with sickle cell disease (SCD), without kidney disease (based on estimated glomerular filtration rate and albuminuria), underwent renal MRI during a vaso-occlusive crisis episode. The imaging data obtained were compared with those for a second MRI performed at steady state (median, 56 [IQR, 37-72] days after the vaso-occlusive crisis MRI). The control group consisted of 10 apparently healthy individuals. MEASUREMENTS: Deoxyhemoglobin level assessed by R2* value was calculated using the blood oxygen level-dependent technique. The intravoxel incoherent motion diffusion-weighted imaging technique was used to calculate D, D*, and F parameters. RESULTS: Median medullary R2* values on steady-state MRI were significantly higher for patients with SCD than for controls (P=0.01) and did not change significantly during the vaso-occlusive crisis. No significant differences in median cortical R2* values were observed. Both cellular integrity (D) and local perfusion (D* and F) were significantly altered in medullary and cortical areas during vaso-occlusive crises in comparison to steady state in patients with SCD. These parameters did not differ significantly between patients with SCD assessed at steady state and the control group. LIMITATIONS: Small sample size, estimation of glomerular filtration rate according to CKD-EPI creatinine equation without adjustment for race. CONCLUSIONS: Deoxyhemoglobin levels in the medullary area are higher in patients with SCD, during vaso-occlusive crises and at steady state, than in controls. Alterations to the tissue perfusion and cellular integrity of renal parenchyma are a common finding during vaso-occlusive crises that provide additional evidence that a vaso-occlusive crisis may be associated with subclinical kidney injury detectable on MRI. PMID- 27663043 TI - [Sociodemographic and mental health risk factors: Global and local conditions according to the Survey results "mental health in the general population" in 18 international locations]. AB - INTRODUCTION: Mental Health in General Population survey (MHGP) is a socio anthropological and epidemiological multicentre research carried out by the WHO Collaborating Centre for Research and Training in Mental Health (Lille, France). It assessed the prevalence of major mental disorders in the general population with 15,747 people aged 18 years and above in 18 sites worldwide: 6 European sites, 4 sites in the Maghreb, 4 sites in the Indian Ocean, 2 sites in the Caribbean and two sites in the Pacific Ocean. OBJECTIVES: To assess the risk of the presence of at least one mental disorder in terms of sociodemographic factors (gender, age, marital status, family income, education level, professional activity, religious practice and social isolation) and location (zone [Europe, North Africa, Indian Ocean, Caribbean Islands and the Indian Ocean Islands] and "investigation site"). METHODOLOGY: Statistical analysis was performed using data collected in 18 international sites of the MHGP survey. Logistic regression was used to model the relationship between sociodemographic and geographic factors and the presence of at least one disorder (mood disorder, anxiety disorder, psychotic disorder, abuse or dependence on alcohol or drugs), evaluated with the Mini International Neuropsychiatric Interview (MINI) diagnostic questionnaire. RESULTS: The prevalence of mental disorders rates vary among 18 sites, ranging from 15.5 % (Andorra) to 60 % (Algiers). The adjusted global epidemiological model (18 cluster sites) confirms a decreased level of risk of at least a psychiatric pathology due to a favorable sociodemographic "profile": marital status (married), family income (higher), age group (60 years and above), educational level (university), gender (male), practice of religion (among believers), employment (exercised). Analysis at geographical situation's level confirms existence of sub socio-geo-demographic models differentiated by ranking and levels of variables' modalities. Classification of variables and their modalities is clearly differentiated not only between 5 zones, but also within each of them depending on the sites that comprise it. This produces differentiated models for each of the 18 survey sites. CONCLUSIONS: The impact of sociodemographic risk factors on mental health is confirmed regardless of World region. However, the implementation of action plans for the prevention of mental disorders requires a detailed understanding of people's needs in terms of the disorder's prevalence, nature and strength of risk factors, at regional and local levels. This observation provides incentives to develop this research axis in world francophone and Latin speaking areas. These epidemiological results can be refined thanks to the data collected in the MHGP surveys about each mental disorder and comorbid conditions, the recourse of populations to assistance or care, as well as results of the socio-anthropological axis. PMID- 27663042 TI - Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD. AB - BACKGROUND: Unlike the case with creatinine, conditions affecting the non glomerular filtration rate (GFR) determinants of low-molecular-weight serum proteins, beta-trace protein (BTP), beta2-microglobulin (B2M), and cystatin C, are not well characterized. STUDY DESIGN: Pooled cross-sectional analysis of 3 studies. SETTING & PARTICIPANTS: 3,156 persons with chronic kidney disease from the MDRD (Modification of Diet in Renal Disease) Study, AASK (African American Study of Kidney Disease and Hypertension), and CRIC (Chronic Renal Insufficiency Cohort) Study. PREDICTORS: Demographic and clinical factors hypothesized to be associated with non-GFR determinants of the filtration markers, selected from literature review and physiologic and clinical considerations. OUTCOMES: Serum creatinine, BTP, B2M, and cystatin C levels. RESULTS: In multivariable-adjusted errors-in-variables regression models that included adjustment for measured GFR (mGFR) and mGFR measurement error, creatinine level had stronger associations with male sex, black race, and higher urine creatinine excretion than the other filtration markers. BTP was associated less strongly with age, similar in direction with sex, and opposite in direction with race than creatinine level. Like cystatin C, B2M level was associated less strongly with age, sex, and race than creatinine level. BTP, B2M, and cystatin C levels were associated more strongly than creatinine level with other factors, including urine protein excretion and weight for BTP, smoking and urine protein excretion for B2M, and smoking for cystatin C. LIMITATIONS: Findings may not be generalizable to populations without chronic kidney disease, and residual confounding with GFR due to incomplete adjustment for GFR measurement error. CONCLUSIONS: Like creatinine, serum levels of low-molecular-weight proteins are affected by conditions other than GFR. Knowledge of these conditions can aid the interpretation of GFR estimates and risk using these markers and guide the use of these filtration markers in developing GFR estimating equations. PMID- 27663044 TI - [Metabolic syndrome and bipolar disorder: Is sleep the missing link?] AB - OBJECTIVE: To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP). METHOD: A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome. RESULTS: Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation. CONCLUSIONS: Circadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP. PMID- 27663045 TI - [Predictors of medication non-adherence among a Moroccan sample of patients with schizophrenia: A cross sectional study]. AB - BACKGROUND: Schizophrenia is a chronic, relapsing, mental disorder, and lack of adherence is a common and severe problem in such patients leadingto global and heavy consequences for patients (relapses, hospitalizations, impaired quality of life...), for the family and for society. Improved understanding of the underlying reasons will help to form intervention strategies relevant to the context. OBJECTIVES: We aimed to assess medication adherence among stable patients suffering from schizophrenia and to identify factors associated with non adherence. METHODS: This is a retrospective cohort study of outpatients with schizophrenia at the psychiatric hospital Ar-razi of Sale (Maroc). The patients were aged over 18, clinically stabilized under the same treatment during the three months prior to inclusion. Data (demographic, clinical and therapeutic) was collected by a questionnaire developed for this purpose. Assessment of adherence and awareness of the disorder (insight) were performed respectively by two validated scales: Medication Adherence Rating Scale the (MARS) and scale Q8. RESULTS: Fourty percent of schizophrenic patients included in our study were not compliant to treatment. Compared to adherent patients, non-adherent patients had history of substance use (57.6 % vs. 42.4 %, P<0.05), were less aware of their disorder (77.8 % vs. 22.2 %, P<0.01), had significantly more drug intake per day (2.4 vs. 1.9, P<0.01), took significantly more tablets per day (2.8 vs. 2.2; P<0.05) and complained of significantly more side effects (43.2 vs. 56.8, P<0.05). A logistic regression model had shown that only side effects, lack of insight, and a history of substances use are significant predictors of poor adherence in patients with schizophrenia. CONCLUSION: The results of this work should guide our efforts to improve adherence in patients with schizophrenia. Waiting for new drugs with fewer side effects and better benefit/risk, some strategies would help to improve adherence to treatment. For example: implementation of strategies to manage psychoactive substance use, structured psycho-educational strategies to improve insight, and training therapists to improve the therapeutic alliance should be established. PMID- 27663046 TI - [Impact of physical disability and concomitant emotional disturbances on post stroke quality of life]. AB - INTRODUCTION: The physical and/or psycho-cognitive changes after stroke may lead to a decline in the quality of life (QOL) of patients. The aims of our study were to evaluate the QOL of stroke survivors and to investigate its relationships with the physical disability degree and the emotional disorders (anxiety and depression). METHODS: We conducted a cross-sectional study, which included 147 patients, followed for stroke that had occurred over the past year, in the outpatient neurology department at the university hospital Habib Bourguiba of Sfax (Tunisia). For each patient, we collected socio-demographic characteristics and clinical and therapeutic data. The quality of life of our patients was assessed using the SF-36 scale. The HAD scale was used to screen for anxiety and depression, whereas the modified Rankin scale was used to measure the degree of disability. RESULTS: The average age of our patients was 60.58 years. The overall mean score of the SF-36 ranged from 20.81 to 89.81 with an average of 55.27. Impaired QOL was found in 68% of patients. The study of the dimensional average scores revealed that only two dimensions of the SF-36 were not altered: physical pain and life and relationship with others. The physical component was slightly more altered than the mental component (41.4 and 42.9 respectively). A minimal disability was found in 32% of patients, while a moderate and severe disability was found in 19% and 21.1% of patients. Anxiety was detected in 55.1% of patients and depression in 67.3% of them. Impaired mental component QOL was significantly correlated with the presence of anxiety (P=0.008) and depression (P<<0.05). The severe degree of disability had a significant negative impact on all areas of QOL except that of life and relationships with others. CONCLUSION: It appears from our study that among the important effects of stroke is the constant deterioration of QOL in its various dimensions. The occurrence of emotional disturbances such as anxiety and depression and the degree of physical disability seem to be predictors of QOL impairment. Therefore, special attention should be given to such patients at higher risk of decline in their QOL. PMID- 27663047 TI - Corrigendum re: "Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Goteborg Randomised Screening Trial" [Eur Urol 2016;70:566-73]. PMID- 27663049 TI - Re: Christof Bernemann, Thomas J. Schnoeller, Manuel Luedeke, et al. Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer. Eur Urol 2017;71:1-3. PMID- 27663048 TI - Robot-assisted Level II-III Inferior Vena Cava Tumor Thrombectomy: Step-by-Step Technique and 1-Year Outcomes. AB - BACKGROUND: Level II-III inferior vena cava (IVC) tumor thrombectomy for renal cell carcinoma is among the most challenging urologic oncologic surgeries. In 2015, we reported the initial series of robot-assisted level III caval thrombectomy. OBJECTIVE: To describe our University of Southern California technique in a step-by-step fashion for robot-assisted IVC level II-III tumor thrombectomy. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five selected patients with renal neoplasm and level II-III IVC tumor thrombus underwent robot-assisted surgery with a minimum 1-yr follow-up (July 2011 to March 2015). SURGICAL PROCEDURE: Our standardized anatomic-based "IVC-first, kidney-last" technique for robot-assisted IVC thrombectomy focuses on minimizing the chances of an intraoperative tumor thromboembolism and major hemorrhage. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline demographics, pathology data, 90-d and 1-yr complications, and oncologic outcomes at last follow-up were assessed. RESULTS AND LIMITATIONS: Robot-assisted IVC thrombectomy was successful in 24 patients (96%) (level III: n=11; level II: n=13); one patient was electively converted to open surgery for failure to progress. Median data included operative time of 4.5h, estimated blood loss was 240ml, hospital stay 4 d; five patients (21%) received intraoperative blood transfusion. All surgical margins were negative. Complications occurred in four patients (17%): two were Clavien 2, one was Clavien 3a, and one was Clavien 3b. All patients were alive at a 16-mo median follow-up (range: 12-39 mo). CONCLUSIONS: Robotic IVC tumor thrombectomy is feasible for level II-III thrombi. To maximize intraoperative safety and chances of success, a thorough understanding of applied anatomy and altered vascular collateral flow channels, careful patient selection, meticulous cross-sectional imaging, and a highly experienced robotic team are essential. PATIENT SUMMARY: We present the detailed operative steps of a new minimally invasive robot-assisted surgical approach to treat patients with advanced kidney cancer. This type of surgery can be performed safely with low blood loss and excellent outcomes. Even patients with advanced kidney cancer could now benefit from robotic surgery with a quicker recovery. PMID- 27663050 TI - Median Nerve Compression by Radial Head Osteophyte. AB - Congenital radial head dislocations are rare, and presentation with late complications is even less common. We present a case of a patient who presented with symptoms and findings of proximal median nerve compression secondary to large osteophytes associated with untreated congenital radial head dislocations. PMID- 27663051 TI - Osseous Anatomy of the Distal Radioulnar Joint: An Assessment Using 3-Dimensional Modeling and Clinical Implications. AB - PURPOSE: Using a novel technique, we assess and describe the distal radioulnar joint (DRUJ) anatomy. The purpose of this study was to provide the anatomic dimensions of the DRUJ and to evaluate contralateral symmetry. METHODS: Computed tomography images of 100 cadaveric forearms were obtained. Three-dimensional models of the radius and ulna were generated and evaluated using 3-dimensional modeling software. Measurements of the radius of curvature of the sigmoid notch (SN) and ulnar head (UH), as well as the length of the SN and volar and dorsal lips were performed in the axial and coronal sequences. In addition, mid-coronal angular measurements were made of the SN and UH to quantify the obliquity of the DRUJ. All coronal measurements were performed with the forearm set to neutral rotation. RESULTS: The average ulnar variance was -0.9 +/- 1.8 mm. The radius of curvature of the UH (8.2 +/- 1.3 mm) was markedly smaller than that of the SN (18.2 +/- 8.5 mm). The length of the SN in coronal sequences increased from volar to dorsal by 65%. The mid-coronal angle (DRUJ obliquity) of the SN and UH measured 6.0 +/- 9.9 degrees and 18.0 +/- 9.9 degrees , respectively. A direct inverse correlation was demonstrated in the obliquity of the DRUJ and ulnar variance. All anatomic measurements were similar when comparing bilateral specimens. CONCLUSIONS: The SN length tends to increase in size from volar to dorsal. Bilateral specimens from the same individual demonstrate similarities and can be cautiously used for comparison. CLINICAL RELEVANCE: The relationships and measurements demonstrated in this study can be a guide when considering reconstructive procedures or dealing with complex fractures involving the DRUJ. PMID- 27663052 TI - Keyhole Revascularization for Treatment of Coronal Plane Fracture of the Lunate in Kienbock Disease. AB - Coronal plane fracture of lunate in Kienbock disease is a challenging problem with no proven treatment. We present a technique for the treatment. A vascularized bone graft from the distal radius employing the fourth and fifth extracompartmental artery pedicles is used as a mechanical support in order to enable fracture union. The technical pearls and pitfalls are described and a clinical case is presented. PMID- 27663053 TI - Incidence and Risk Factors for Volar Wrist Ganglia in the U.S. Military and Civilian Populations. AB - PURPOSE: To identify the incidence and demographic factors associated with volar wrist ganglia in both military and civilian beneficiary populations. METHODS: The U.S. Department of Defense Management Analysis and Reporting Tool (M2) accesses a comprehensive database of all health care visits by military personnel and their dependents. Because there is no specific code for ganglions of the wrist, the database was searched for all military personnel and civilian beneficiaries with an International Classification of Diseases, 9th Revision, diagnosis of 727.41 (ganglion of a joint) or 727.43 (ganglion, unspecified location) between 2009 and 2014. Two random samples of 1000 patients were selected from both the military and the civilian beneficiary cohorts, and their electronic medical records were examined to identify those with volar wrist ganglia. The proportion of volar wrist ganglia was then applied to the overall population data to estimate the total incidence with a 95% confidence interval and 5% margin of error. Unadjusted incidence rates and adjusted incidence rate ratios were determined using Poisson regression, controlling for age, sex, branch of military service, and military seniority. RESULTS: The unadjusted incidence of volar wrist ganglia is 3.72 per 10,000 person-years (0.04%/y) in female civilian beneficiaries, 1.04 per 10,000 person-years (0.01%/y) in male civilian beneficiaries, 7.98 per 10,000 person years (0.08%/y) in female military personnel, and 3.73 per 10,000 person-years (0.04%/y) in male military personnel. When controlled for age, military personnel have a 2.5-times increased rate of volar wrist ganglia, and women have a 2.3 times increased rate. In the military cohort, female sex, branch of service, and seniority were significantly associated with the diagnosis of a volar wrist ganglion when controlled for age. In the civilian beneficiary cohort, only female sex was significant. CONCLUSIONS: Military service members have higher rates of volar wrist ganglia diagnoses than their age- and sex-matched civilian counterparts. Women are significantly more likely to be diagnosed with a volar wrist ganglion, regardless of age or military status. CLINICAL RELEVANCE: The epidemiology of volar wrist ganglia is poorly defined, and few studies have firmly defined demographic factors associated with the diagnosis. We provide the overall incidence rate of the diagnosis and report a significant association with female sex even when controlled for age. PMID- 27663055 TI - Effects on the Distal Radioulnar Joint of Ablation of Triangular Fibrocartilage Complex Tears With Radiofrequency Energy. AB - PURPOSE: This cadaver study investigated the temperature profile in the wrist joint and distal radioulnar joint (DRUJ) during radiofrequency energy (RFE) application for triangular fibrocartilage complex resection. METHODS: An arthroscopic partial resection of the triangular fibrocartilage complex using monopolar and bipolar RFE was simulated in 14 cadaver limbs. The temperature was recorded simultaneously in the DRUJ and at 6 other anatomic locations of the wrist during RFE application. RESULTS: The mean temperature in the DRUJ was 43.3 +/- 8.2 degrees C for the bipolar system in the ablation mode (60 W) and 30.4 +/- 3.4 degrees C for the monopolar system in the cut mode (20 W) after 30 seconds. The highest measured temperature in the DRUJ was 54.3 degrees C for the bipolar system and 68.1 degrees C for the monopolar system. CONCLUSIONS: The application of RFE for debridement or resection of the triangular fibrocartilage complex in a clinical setting can induce peak temperatures that might cause damage to the cartilage of the DRUJ. Bipolar systems produce higher mean temperatures than monopolar devices. CLINICAL RELEVANCE: RFE application increases the mean temperature in the DRUJ after 30 seconds to a level that may jeopardize cartilage tissue. PMID- 27663054 TI - Radial to Axillary Nerve Transfers: A Combined Case Series. AB - PURPOSE: Loss of active shoulder abduction after brachial plexus or isolated axillary nerve injury is associated with a severe functional deficit. The purpose of this 2-center study was to retrospectively evaluate restoration of shoulder abduction after transfer of a radial nerve branch to the axillary nerve for patients after brachial plexus or axillary nerve injury. METHODS: Patients who underwent transfer of a radial nerve branch to the anterior branch of the axillary nerve between 2004 and 2014 were reviewed. A total of 27 patients with an average follow-up of 22 months were included. Outcome measures included pre- and postoperative shoulder abduction and triceps strength and active and passive shoulder range of motion. RESULTS: Shoulder abduction strength increased after surgery in 89% of patients. Average preoperative shoulder abduction was 12 degrees compared with 114 degrees after surgery. Twenty-two of 27 patients (81.5%) achieved at least M3 strength, with 17 of 27 patients (62.9%) achieving M4 strength. No differences were observed when subgroup analysis was performed for isolated nerve transfer versus multiple nerve transfer, mechanism of injury, injury level, branch of radial nerve transferred, or time from injury to surgery. A negative correlation was found comparing increasing age and both shoulder abduction strength and active shoulder abduction. No patients lost triceps strength after surgery. There were 4 patients who achieved no significant gain in shoulder abduction or deltoid strength and were deemed failures. No postoperative complications occurred. CONCLUSIONS: Transfer of a branch of the radial nerve to the anterior branch of the axillary nerve was successful in improving shoulder abduction strength and active shoulder motion in the majority of the patients with brachial plexus or isolated axillary nerve injury. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 27663056 TI - RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction. AB - Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a common cause of exertional rhabdomyolysis, accounting for up to 30% of rhabdomyolysis episodes in otherwise healthy individuals. Common triggers are exercise and heat and, less frequently, viral infections, alcohol and drugs. Most subjects are normally strong and have no personal or family history of malignant hyperthermia. Heat intolerance and cold-induced muscle stiffness may be a feature. Recognition of this (probably not uncommon) rhabdomyolysis cause is vital for effective counselling, to identify potentially malignant hyperthermia susceptible individuals and to adapt training regimes. Studies in various animal models provide insights regarding possible pathophysiological mechanisms and offer therapeutic perspectives. PMID- 27663057 TI - Familial amyloid polyneuropathy: When does it stop to be asymptomatic and need a treatment? AB - Transthyretin familial amyloid polyneuropathy (FAP) is a rare disease with autosomal transmission due to point mutation of the transthyretin (TTR) gene. It is the most disabling hereditary neuropathy affecting sensory, motor and autonomic nerves, and is irreversible and fatal within 7 to 12 years of onset in the absence of therapy. Diagnosis is usually delayed for 1-5 years because the onset is usually insidious, and a positive family history is lacking in 50% of late-onset cases. Penetrance is variable, and depends of the age of the carrier and age of onset in family members. Two treatments are available: liver transplantation, to suppress the main source of systemic production of mutant TTR; and TTR tetramer stabilizer drugs, to avoid the release of highly amyloidogenic monomers and oligomers. These therapies are able to stop or slow the progression of the disease in its early stages. Genetic counseling is crucial to detect carriers at risk of developing the disease. The European network for TTR-FAP recommends careful baseline assessment by questionnaire, clinical examination and neurophysiological tests, and periodic consultations to detect the onset of disease in time to start anti-amyloid therapy after biopsy findings of amyloid deposition. A therapeutic educational program is important for improving patients' awareness. Patients are considered symptomatic and ill when they themselves perceive symptoms or changes, including changes from baseline measurements on neurophysiological tests, followed by findings of amyloid deposition on biopsy. The most sensitive biopsies are from the labial salivary gland and skin. PMID- 27663059 TI - Exercise training in metabolic myopathies. AB - Metabolic myopathies encompass muscle glycogenoses (GSD) and disorders of muscle fat oxidation (FAOD). FAODs and GSDs can be divided into two main clinical phenotypes; those with static symptoms related to fixed muscle weakness and atrophy, and those with dynamic, exercise-related symptoms that are brought about by a deficient supply of ATP. Together with mitochondrial myopathies, metabolic myopathies are unique among muscle diseases, as the limitation in exercise performance is not solely caused by structural damage of muscle, but also or exclusively related to energy deficiency. ATP consumption can increase 50-100 fold in contracting, healthy muscle from rest to exercise, and testing patients with exercise is therefore an appropriate approach to disclose limitations in work capacity and endurance in metabolic myopathies. Muscles rely almost exclusively on muscle glycogen in the initial stages of exercise and at high work intensities. Thus, patients with GSDs typically have symptoms early in exercise, have low peak work capacities and develop painful contractures in exercised muscles. Muscle relies on fat oxidation at rest and to a great extent during prolonged exercise, and therefore, patients with FAODs typically develop symptoms later in exercise than patients with GSDs. Due to the exercise-related symptoms in metabolic myopathies, patients generally have been advised to shun physical training. However, immobility is associated with multiple health issues, and may even cause unwanted metabolic adaptations, such as increased dependence on glycogen use and a reduced capacity for fatty acid oxidation, which is detrimental in GSDs. Training has not been studied systematically in any FAODs and in just a few GSDs. However, studies on single bouts of exercise in most metabolic myopathies show that particularly moderate intensity aerobic exercise is well tolerated in these conditions. Even low-intensity resistance training of short duration is tolerated in McArdle disease. Training in patients with FAOD potentially can also expand the metabolic bottleneck by increasing expression of the defective, but partially functional enzyme. Exercise performance in metabolic myopathies can be improved by different fuel supplementations and dietary interventions and should be considered as adjunct therapy to exercise training. PMID- 27663058 TI - Muscle MRI of facioscapulohumeral dystrophy (FSHD): A growing demand and a promising approach. AB - Facioscapulohumeral muscular dystrophy (FSHD), an inherited and progressive muscle disorder, is among the most common hereditary muscle disorders. From a clinical vantage point, FSHD is characterized by weakness of the facial, shoulder (often with scapular winging), arm (including biceps and triceps) and abdominal muscles. Forearm muscles are usually spared and weakness is usually asymmetrical. Over the past few decades, muscle magnetic resonance imaging (MRI) has become established as a reliable and accurate noninvasive tool for the diagnosis and assessment of progression in neuromuscular diseases, showing specific patterns of muscle involvement for a number of myopathies. More recently, MRI has been used to noninvasively identify quantitative biomarkers, allowing evaluation of the natural progression of disease and assessment of therapeutic interventions. In the present review, the intention was to present the most significant MRI developments related to diagnosis and pattern recognition in FSHD and to discuss its capacity to provide outcome measures. PMID- 27663060 TI - What have we learned about glycogenosis in recent years? AB - The field of glycogenosis has been greatly expanded over the past few years with the discovery of new metabolic diseases that have allowed new metabolic pathways to be deciphered. Described here are the clinical and pathological features of four recently described muscle glycogenoses caused by GYS1, GYG1, RBCK1 and PGM1 gene mutations. The initial steps of glycogen synthesis are involved in deficiencies of glycogenin-1 (GYG1) and muscle glycogen synthase (GYS1). Phosphoglucomutase deficiency disrupts two metabolic pathways: the connection between galactose and glycogen on the one hand, and glucose metabolism on the other. However, the metabolic consequences of mutations in the ubiquitin ligase gene RBCK1 are still poorly understood. PMID- 27663061 TI - Unified Database for Rejected Image Analysis Across Multiple Vendors in Radiography. AB - Reject rate analysis has been part of radiography departments' quality control since the days of screen-film radiography. In the era of digital radiography, one might expect that reject rate analysis is easily facilitated because of readily available information produced by the modality during the examination procedure. Unfortunately, this is not always the case. The lack of an industry standard and the wide variety of system log entries and formats have made it difficult to implement a robust multivendor reject analysis program, and logs do not always include all relevant information. The increased use of digital detectors exacerbates this problem because of higher reject rates associated with digital radiography compared with computed radiography. In this article, the authors report on the development of a unified database for vendor-neutral reject analysis across multiple sites within an academic institution and share their experience from a team-based approach to reduce reject rates. PMID- 27663062 TI - The cerebellum and language: Persistent themes and findings. AB - This special issue brings together a set of articles that focus on the cerebellum and language. Contributors were specifically invited from relative newcomers to this research topic, as a way to draw attention to perspectives and findings that might otherwise be overlooked. This editorial provides an overview of the issue from a historical context that draws upon more than 25 years of research on the linguistic cerebellum. PMID- 27663063 TI - Reliability and validity of a new dexterity questionnaire (DextQ-24) in Parkinson's disease. AB - BACKGROUND: Patients with Parkinson's disease exhibit disturbed dexterity. Validated self-reported outcomes for dexterity in Parkinson's disease are lacking. The aim of this study was to investigate the reliability, content and construct validity of a new Dexterity Questionnaire 24. METHODS: One hundred and three patients with Parkinson's disease completed the Dexterity Questionnaire 24 (score range 24-96), at baseline and four weeks later. The internal consistency was determined. Test-retest reliability was assessed in a subgroup (N = 44). Standard error of measurements and the minimal detectable change were defined. The construct validity was examined in the whole group (N = 103). Floor and ceiling effects were investigated. RESULTS: The internal consistency of the Dexterity Questionnaire 24 was high (alpha = 0.91). High test-retest reliability was found (Intra Class Correlation Coefficient = 0.91, Confidence interval: 0.84 0.95). Standard error of measurement was 2.9 and minimal detectable change was 8 points. (i.e., 11%). Good structural, convergent and divergent validity of the Dexterity questionnaire 24 was found (r = 0.73 with Activities of Daily Living subscale of the Parkinson's Disease Questionnaire-39, and r = 0.66, and r = 0.50, p-values all < 0.0001, respectively with the subscales II and III of the Movement Disorders Society-Unified Parkinson Disease Rating Scale). Low not significant correlations were found between the Dexterity Questionnaire 24 and the subscales stigma and social support (r = 0.20, and r = 0.14 respectively). No floor or ceiling effects were found for the total Dexterity Questionnaire 24. CONCLUSION: The Dexterity Questionnaire 24 is valid and reliable for evaluating dexterity in patients with Parkinson's disease. PMID- 27663064 TI - Is Pupillary Response a Biomarker for Effort and Defeatist Attitudes in Patients With Schizophrenia? PMID- 27663065 TI - What Are Sleep Spindle Deficits Telling Us About Schizophrenia? PMID- 27663066 TI - The Role of the Corpus Callosum in Psychosis. PMID- 27663067 TI - Psychiatric Pharmacogenomics: How Close Are We? PMID- 27663068 TI - Revisiting the Inverted-U Hypothesis of Working Memory Activation in Schizophrenia. PMID- 27663069 TI - Adrift in the world of therapeutic apheresis: One center's experience in using arterio-venous fistulas during apheresis procedures. AB - Therapeutic plasma exchange (TPE) is often an isolated specialty with very little research, especially in regard to the mode of access. This lack of information drove this attempt at reviewing the use of arterio-venous fistulas (AVF) in TPE, and specifically the issue of monitoring the accesses patency. Using a Transonic(r), we attempted to obtain a reading, using the Spectra OptiaTM on a patient's access. Unfortunately, due to the limitations of the equipment, we were unable to get a reading. Our conclusion is that we will have to monitor using other approaches, such as physical assessment and ultrasound. PMID- 27663071 TI - Endogenous TRPV1 stimulation leads to the activation of the inositol phospholipid pathway necessary for sustained Ca2+ oscillations. AB - Sensory neuron subpopulations as well as breast and prostate cancer cells express functional transient receptor potential vanilloid type 1 (TRPV1) ion channels; however little is known how TRPV1 activation leads to biological responses. Agonist-induced activation of TRPV1 resulted in specific spatiotemporal patterns of cytoplasmic Ca2+ signals in breast and prostate cancer-derived cells. Capsaicin (CAPS; 50MUM) evoked intracellular Ca2+ oscillations and/or intercellular Ca2+ waves in all cell lines. As evidenced in prostate cancer Du 145 cells, oscillations were largely dependent on the expression of functional TRPV1 channels in the plasma membrane, phospholipase C activation and on the presence of extracellular Ca2+ ions. Concomitant oscillations of the mitochondrial matrix Ca2+ concentration resulted in mitochondria energization evidenced by increased ATP production. CAPS-induced Ca2+ oscillations also occurred in a subset of sensory neurons, yet already at lower CAPS concentrations (1MUM). Stimulation of ectopically expressed TRPV1 channels in CAPS-insensitive NIH-3T3 cells didn't provoke CAPS-triggered Ca2+ oscillations; rather it resulted in low-magnitude, long-lasting elevations of the cytosolic Ca2+ concentration. This indicates that sole TRPV1 activation is not sufficient to generate Ca2+ oscillations. Instead the initial TRPV1-mediated signal leads to the activation of the inositol phospholipid pathway. This in turn suffices to generate a biologically relevant frequency-modulated Ca2+ signal. PMID- 27663070 TI - Gevokizumab in the Treatment of Autoimmune Non-necrotizing Anterior Scleritis: Results of a Phase I/II Clinical Trial. AB - PURPOSE: To evaluate the safety and potential efficacy of gevokizumab, an anti interleukin 1beta (IL-1beta) monoclonal antibody, in the treatment of active, noninfectious, non-necrotizing anterior scleritis. DESIGN: Phase 1/2, open label, nonrandomized, prospective, single-arm pilot trial. METHODS: Eight patients with active, noninfectious, non-necrotizing anterior scleritis with a scleral inflammatory grade of +1 to +3 in at least 1 eye were enrolled. In 1 patient both eyes were enrolled, for a total of 9 eyes (4 eyes with +1, 1 eye with +2, and 4 eyes with +3). Patients received 1 subcutaneous injection of 60 mg gevokizumab at baseline and then every 4 weeks for 12 weeks. Complete physical and ocular examinations were performed at each visit. The primary outcome was at least a 2 step reduction or reduction to grade 0 in scleral inflammation on a 0 to +4 scale according to a standardized photographic scleritis grading system by 16 weeks in the study eye compared to baseline. Secondary outcomes included changes in visual acuity, intraocular pressure, and trends in scleral grading. Participants who met the primary outcome were eligible to continue in the study for up to 52 weeks and received additional gevokizumab injections every 4 weeks until week 36, followed by 2 safety visits at weeks 40 and 52. RESULTS: Seven eyes from 7 patients met the primary outcome within a median time of 2 weeks following the first gevokizumab injection. No definitive changes in visual acuity or intraocular pressure were identified. There were no serious adverse events related to the study drug. A total of 43 adverse effects were reported, with 93% described as mild, 95% as nonocular, and only 14% deemed possibly caused by the investigational treatment. CONCLUSIONS: The results of this small study suggest that blockage of IL-1beta using gevokizumab may be beneficial in treating active, noninfectious anterior scleritis and that gevokizumab is well tolerated. Larger randomized trials are warranted to assess the true efficacy of gevokizumab in the treatment of non-necrotizing anterior scleritis. PMID- 27663072 TI - Quinolinic acid neurotoxicity: Differential roles of astrocytes and microglia via FGF-2-mediated signaling in redox-linked cytoskeletal changes. AB - QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling. In mixed cultures (astrocyte, neuron, microglia), QUIN-induced FGF-2 increased level failed to activate Erk and promoted cytoskeletal destabilization. The effects of QUIN in mixed cultures involved redox imbalance upstream of Erk activation. Decreased connexin 43 (Cx43) immunocontent and functional GJs, was also coincident with disruption of the cytoskeleton in primary astrocytes and mixed cultures. We postulate that in interacting astrocytes and neurons the cytoskeleton is preserved against the insult of QUIN by activation of FGF-2/Erk signaling and proper cell-cell interaction through GJs. In mixed cultures, the FGF-2/Erk signaling is blocked by the redox imbalance associated with microglial activation and disturbed cell communication, disrupting the cytoskeleton. Thus, QUIN signal activates differential mechanisms that could stabilize or destabilize the cytoskeleton of striatal astrocytes and neurons in culture, and glial cells play a pivotal role in these responses preserving or disrupting a combination of signaling pathways and cell-cell interactions. Taken together, our findings shed light into the complex role of the active interaction of astrocytes, neurons and microglia in the neurotoxicity of QUIN. PMID- 27663073 TI - Structural and functional characterisation of the cyanobacterial PetC3 Rieske protein family. AB - The cyanobacterium Synechocystis PCC 6803 possesses three Rieske isoforms: PetC1, PetC2 and PetC3. While PetC1 and PetC2 have been identified as alternative subunits of the cytochrome b6f complex (b6f), PetC3 was localized exclusively within the plasma membrane. The spatial separation of PetC3 from the photosynthetic and respiratory protein complexes raises doubt in its involvement in bioenergetic electron transfer. Here we report a detailed structural and functional characterization of the cyanobacterial PetC3 protein family indicating that PetC3 is not a component of the b6f and the photosynthetic electron transport as implied by gene annotation. Instead PetC3 has a distinct function in cell envelope homeostasis. Especially proteomic analysis shows that deletion of petC3 in Synechocystis PCC 6803 primarily affects cell envelope proteins including many nutrient transport systems. Therefore, the observed downregulation in the photosynthetic electron transport - mainly caused by photosystem 2 inactivation - might constitute a stress adaptation. Comprehensive in silico sequence analyses revealed that PetC3 proteins are periplasmic lipoproteins tethered to the plasma membrane with a subclass consisting of soluble periplasmic proteins, i.e. their N-terminal domain is inconsistent with their integration into the b6f. For the first time, the structure of PetC3 was determined by X-ray crystallography at an atomic resolution revealing significant high similarities to non-b6f Rieske subunits in contrast to PetC1. These results suggest that PetC3 affects processes in the periplasmic compartment that only indirectly influence photosynthetic electron transport. For this reason, we suggest to rename "Photosynthetic electron transport Chain 3" (PetC3) proteins as "periplasmic Rieske proteins" (Prp). PMID- 27663074 TI - Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2). AB - Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG. PMID- 27663075 TI - CCAAT/enhancer binding protein beta negatively regulates progesterone receptor expression in human glioblastoma cells. AB - Many progesterone (P4) actions are mediated by its intracellular receptor (PR), which has two isoforms (PR-A and PR-B) differentially transcribed from separate promoters of a single gene. In glioblastomas, the most frequent and aggressive brain tumors, PR-B is the predominant isoform. In an in silico analysis we showed putative CCAAT/Enhancer Binding Protein (C/EBP) binding sites at PR-B promoter. We evaluated the role of C/EBPbeta in PR-B expression regulation in glioblastoma cell lines, which expressed different ratios of PR and C/EBPbeta isoforms (LAP1, LAP2, and LIP). ChIP assays showed a significant basal binding of C/EBPbeta, specific protein 1 (Sp1) and estrogen receptor alpha (ERalpha) to PR-B promoter. C/EBPbeta knockdown increased PR-B expression and treatment with estradiol (E2) reduced C/EBPbeta binding to the promoter and up-regulated PR-B expression. P4 induced genes were differently regulated when CEBP/beta was silenced. These data show that C/EBPbeta negatively regulates PR-B expression in glioblastoma cells. PMID- 27663077 TI - Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LbetaT2 cells. AB - The mammalian target of rapamycin (mTOR) assembles into two different multi protein complexes, mTORC1 and mTORC2. The mTORC2 complex is distinct due to the unique expression of the specific core regulatory protein Rictor (rapamycin insensitive companion of mTOR). mTORC2 has been implicated in regulating actin cytoskeletal reorganization but its role in gonadotrope function is unknown. Using the gonadotrope-derived LbetaT2 cell line, we find that the GnRH agonist buserelin (GnRHa) phosphorylates both mTOR and Rictor. Interestingly, inhibition of mTORC2 blunts GnRHa-induced cyto-architectural rearrangements. Coincident with blunting of actin reorganization, inhibition of mTORC2 also attenuates GnRHa mediated activation of both protein kinase C (PKC) and extracellular signal regulated kinase (ERK). Collectively, our data suggests that GnRHa-mediated mTORC2 activation is important in facilitating actin reorganization events critical for initiating PKC activity and subsequent ERK phosphorylation in the gonadotrope-derived LbetaT2 cell line. PMID- 27663078 TI - The effects of levonorgestrel on FSH-stimulated primary rat granulosa cell cultures through gene expression profiling are associated to hormone and folliculogenesis processes. AB - Levonorgestrel (LNG), a synthetic progestin, is used in emergency contraception (EC). The mechanism is preventing or delaying ovulation at the level of the hypothalamic pituitary unit; however, little knowledge exists on LNG effects at the ovary. The aim of this study was to identify the effects of LNG on FSH induced 17beta-estradiol (E2) production, including LNG-mediated changes on global gene expression in rat granulosa cells (GC). Isolated GC from female Wistar rats were incubated in vitro in the presence or absence of human FSH and progestins. At the end of incubations, culture media and cells were collected for E2 and mRNA quantitation. The results showed the ability of LNG to inhibit both hFSH-induced E2 production and aromatase gene expression. Microarray analysis revealed that LNG treatment affects GC functionality particularly that related to folliculogenesis and steroid metabolism. These results may offer additional evidence for the mechanisms of action of LNG as EC. PMID- 27663076 TI - Ovarian transcriptome associated with reproductive senescence in the long-living Ames dwarf mice. AB - The aim of the current work was to evaluate the ovarian follicle reserve and the ovarian transcriptome in Ames dwarf (df/df) mice. The results suggest a delayed ovarian aging in df/df mice compared to normal (N) mice. Although a high number of genes were differentially expressed during aging of N mice, only a small fraction of these changed with aging in df/df mice. These alterations involved more than 500 categorized biological processes. The majority of these biological processes, including inflammatory/immune responses, were up-regulated with aging in N mice, while old df/df mice were characterized by down-regulation of these same processes in comparison to age matched N mice. However, biological processes related to DNA damage and repairing were commonly down-regulated with aging in both genotypes. In conclusion, delayed ovarian aging in long-living df/df mice was associated with reduced expression of genes related to the inflammatory and immune responses. PMID- 27663079 TI - Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. AB - BACKGROUND: Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate to-severe plaque psoriasis. OBJECTIVE: To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks. METHODS: Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study. RESULTS: Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with >=90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% [P < .0001]); PASI 100 responses were 46% versus 36% (P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% (P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index [DLQI], EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab (P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable. LIMITATIONS: There was no placebo arm. CONCLUSION: In this head-to head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile. PMID- 27663080 TI - S-TEAMS: A Truly Multiprofessional Course Focusing on Nontechnical Skills to Improve Patient Safety in the Operating Theater. AB - BACKGROUND: Possessing adequate nontechnical skills (NTS) in operating theaters is of increasing interest to health care professionals, yet these are rarely formally taught. Teams make human errors despite technical expertise and knowledge, compromising patient safety. We designed a 1-day, multiprofessional, multidisciplinary course to teach, practice, and apply these skills through simulation. METHODS: The course, "S-TEAMS," comprised a morning of lectures, case studies, and interactive teamworking exercises. The afternoon divided the group into multiprofessional teams to rotate around simulated scenarios. During the scenarios, teams were encouraged to focus on NTS, including communication strategies, situational awareness, and prompts such as checklists. A thorough debrief with experienced clinician observers followed. Data was collected through self-assessments, immediate and 6-month feedback to assess whether skills continued to be used and their effect on safety. FINDINGS: In total, 68 health care professionals have completed the course thus far. All participants felt the course had a clear structure and that learning objectives were explicit. Overall, 95% felt the scenarios had good or excellent relevance to clinical practice. Self assessments revealed a 55% increase in confidence for "speaking up" in difficult situations. Long-term data revealed 97% of the participants continued to use the skills, with 88% feeling the course had prevented them from making errors. Moreover, 94% felt the course had directly improved patient safety. CONCLUSIONS: There is a real demand and enthusiasm for developing NTS within the modern theater team. The simple and easily reproducible format of S-TEAMS is sustainable and inclusive, and crucially, the skills taught continue to be used in long term to improve patient safety and teamworking. PMID- 27663081 TI - Finding Value in Surgical Didactics: Longitudinal Resident Feedback From Case Based and Traditional Lectures in an Orthopaedic Residency. AB - OBJECTIVE: To evaluate orthopedic resident perceptions of a didactic curriculum presented in traditional and case-based formats. DESIGN: Prospective cohort study using anonymous web-based survey after each conference evaluating resident perceptions of faculty participation, didactic delivery, content, and overall conference value. Conferences were structured as primarily case-based or traditional lecture. Logistic analysis was performed to determine factors predictive of rating a conference as valuable time spent. SETTING: Orthopedic residency training program at single institution over an academic year. PARTICIPANTS: Orthopedic residents in postgraduate training year 1 to 5 attending mandatory didactic conference. RESULTS: Cased-based conferences received higher Likert ratings on residents' perception of faculty participation, instructor delivery, and improvement in topic understanding when compared to traditional lecture-based conferences (p < 0.0001 for each factor). Residents also were more likely to rate case-based conferences as valuable time spent (p < 0.0001). In our logistic model, factors associated with a negative likelihood of rating a conference as valuable were lecture format (odds ratio [OR] = 0.155, 95% CI: 0.115-0.208), PGY-2 level presenter (OR = 0.288, 95% CI: 0.169-0.490), and PGY-3 level presenter (OR = 0.433, 95% CI: 0.269-0.696). Timing in the year, surgical subspeciality, and conference identity were not significant predictors of conference value rating. CONCLUSIONS: Longitudinal resident feedback demonstrates highly favorable resident perceptions toward case-based formats in didactic sessions. Junior levels residents are not perceived as effective as senior residents and faculty in presenting material in either format. These methods allow for a dynamic approach to identifying strengths and weaknesses in a resident curriculum as a well as a means for more focused and real-time improvements. PMID- 27663082 TI - An Overview of Cultural Competency Curricula in ACGME-accredited General Surgery Residency Programs. AB - OBJECTIVE: Cultural competency(CC) in surgical residency curricula is not the novel idea it was fourteen years ago when the ACGME challenged program directors to teach and assess six core competencies. CC is recognized as a component of "patient care", "professionalism", and "interpersonal and communication skills." The results of five programs (2004-2012) with CC curricula were identified in a 2013 paper by Ly and Chun. The primary objective of this paper is to provide the current status of CC curricula in general surgery residency programs. DESIGN: Three sources were used for this study. First, a four question survey on the current status of CC education was sent to program directors of ACGME-accredited surgery residency programs. Second, the lead authors from five programs previously reported in the 2013 paper were interviewed. Third, the survey mentioned above was resent to 52 residency programs who implemented New York University's (NYU) SPICE program, which has a CC component. PARTICIPANTS: Participants for the survey consisted of program directors of ACGME-accredited surgery residency programs. The interviews were conducted with the corresponding authors from the previous study by Ly and Chun. RESULTS: Of the 256 surveyed, nine responded; seven stated that CC is not taught formally at their institution while four stated that they do not feel any part of CC curricula is missing from their program. Due to the low response rate, we identified and conducted interviews with general surgery residency programs with CC curricula. Of the five programs contacted, only three remain active and utilize Objective Structured Clinical Examinations (OSCEs) to teach cultural competency. One of the three, the SPICE program at NYU, has expanded to 52 other residency programs in the US. CONCLUSIONS: Although the importance of CC has been identified in general surgery, formal curricula and documentation of implementation remains elusive. PMID- 27663083 TI - Sequential Participation in a Multi-Institutional Mock Oral Examination Is Associated With Improved American Board of Surgery Certifying Examination First Time Pass Rate. AB - OBJECTIVE: We sought to determine whether sequential participation in a multi institutional mock oral examination affected the likelihood of passing the American Board of Surgery Certifying Examination (ABSCE) in first attempt. DESIGN: Residents from 3 academic medical centers were able to participate in a regional mock oral examination in the fall and spring of their fourth and fifth postgraduate year from 2011 to 2014. Candidate's highest composite score of all mock orals attempts was classified as risk for failure, intermediate, or likely to pass. Factors including United States Medical Licensing Examination steps 1, 2, and 3, number of cases logged, American Board of Surgery In-Training Examination performance, American Board of Surgery Qualifying Examination (ABSQE) performance, number of attempts, and performance in the mock orals were assessed to determine factors predictive of passing the ABSCE. RESULTS: A total of 128 mock oral examinations were administered to 88 (71%) of 124 eligible residents. The overall first-time pass rate for the ABSCE was 82%. There was no difference in pass rates between participants and nonparticipants. Of them, 16 (18%) residents were classified as at risk, 47 (53%) as intermediate, and 25 (29%) as likely to pass. ABSCE pass rate for each group was as follows: 36% for at risk, 84% for intermediate, and 96% for likely pass. The following 4 factors were associated with first-time passing of ABSCE on bivariate analysis: mock orals participation in postgraduate year 4 (p = 0.05), sequential participation in mock orals (p = 0.03), ABSQE performance (p = 0.01), and best performance on mock orals (p = 0.001). In multivariable logistic regression, the following 3 factors remained associated with ABSCE passing: ABSQE performance, odds ratio (OR) = 2.9 (95% CI: 1.3-6.1); mock orals best performance, OR = 1.7 (1.2-2.4); and participation in multiple mock oral examinations, OR = 1.4 (1.1-2.7). CONCLUSIONS: Performance on a multi-institutional mock oral examination can identify residents at risk for failure of the ABSCE. Sequential participation in mock oral examinations is associated with improved ABSCE first-time pass rate. PMID- 27663084 TI - The Effect of Patient Education on the Perceptions of Resident Participation in Surgical Care. AB - OBJECTIVE: To decipher if patient attitudes toward resident participation in their surgical care can be improved with patient education regarding resident roles, education, and responsibilities. DESIGN: An anonymous questionnaire was created and distributed in outpatient surgery clinics that had residents involved with patient care. In total, 3 groups of patients were surveyed, a control group and 2 intervention groups. Each intervention group was given an informational pamphlet explaining the role, education, and responsibilities of residents. The first pamphlet used an analogy-based explanation. The second pamphlet used literature citations and statistics. SETTING: Keesler Medical Center, Keesler AFB, MS. University of Texas Health Science Center at San Antonio, San Antonio, TX. PARTICIPANTS: A total of 454 responses were collected and analyzed-211 in the control group, 118 in the analogy pamphlet group, and 125 in the statistics pamphlet group. RESULTS: Patients had favorable views of residents assisting with their surgical procedures, and the majority felt that outcomes were the same or better regardless of whether they read an informational pamphlet. Of all the patients surveyed, 80% agreed or strongly agreed that they expect to be asked permission for residents to be involved in their care. Further, 52% of patients in the control group agreed or strongly agreed to a fifth-year surgery resident operating on them independently for routine procedures compared to 62% and 65% of the patients who read the analogy pamphlet and statistics pamphlet, respectively (p = 0.05). When we combined the 2 intervention groups compared to the control group, this significant difference persisted (p = 0.02). CONCLUSION: Most patients welcome resident participation in their surgical care, but they expect to be asked permission for resident involvement. Patient education using an information pamphlet describing resident roles, education, and responsibilities improved patient willingness to allow a chief resident to operate independently. PMID- 27663085 TI - Evidence-based pathology in its second decade: toward probabilistic cognitive computing. AB - Evidence-based pathology advocates using a combination of best available data ("evidence") from the literature and personal experience for the diagnosis, estimation of prognosis, and assessment of other variables that impact individual patient care. Evidence-based pathology relies on systematic reviews of the literature, evaluation of the quality of evidence as categorized by evidence levels and statistical tools such as meta-analyses, estimates of probabilities and odds, and others. However, it is well known that previously "statistically significant" information usually does not accurately forecast the future for individual patients. There is great interest in "cognitive computing" in which "data mining" is combined with "predictive analytics" designed to forecast future events and estimate the strength of those predictions. This study demonstrates the use of IBM Watson Analytics software to evaluate and predict the prognosis of 101 patients with typical and atypical pulmonary carcinoid tumors in which Ki-67 indices have been determined. The results obtained with this system are compared with those previously reported using "routine" statistical software and the help of a professional statistician. IBM Watson Analytics interactively provides statistical results that are comparable to those obtained with routine statistical tools but much more rapidly, with considerably less effort and with interactive graphics that are intuitively easy to apply. It also enables analysis of natural language variables and yields detailed survival predictions for patient subgroups selected by the user. Potential applications of this tool and basic concepts of cognitive computing are discussed. PMID- 27663086 TI - Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. AB - Penile squamous cell carcinoma (SCC) is primarily treated by surgical resection. Locally advanced and metastatic diseases require a multidisciplinary treatment approach. However, mortality and morbidity remain high, and novel molecular and immunotherapeutic targets are actively being sought. We investigated the expression of immune-checkpoint markers in penile cancers. Fifty-three invasive penile SCCs diagnosed between 1985 and 2013 were retrieved from our surgical pathology archives. Representative formalin-fixed, paraffin-embedded archival blocks were used for the construction of 2 high-density tissue microarrays. Tissue microarrays were stained with immunohistochemistry for PD-L1, FOXP3, CD8, and Ki-67. PD-L1 was investigated using rabbit monoclonal anti-PD-L1 antibody (Cell Signaling, Boston, MA; E1L3N, 1:100). Overall, 21 (40%) of 53 penile SCCs had positive PD-L1 expression. PD-L1 was expressed by a significant proportion of advanced penile SCC. Forty-four percent (15/34) of stage pT2 or more SCC and 38% (6/16) of tumors with lymph node metastasis were positive for PD-L1. PD-L1 expression did not correlate with patient age, tumor location, histologic subtype, tumor stage, anatomic depth of invasion, or tumor grade. FOXP3 expression in tumoral immune cells was found in 26 (49%) of 53 cases. FOXP3 expression in stromal immune cells correlated with tumor thickness (P = .0086). The ratio of CD8/FOXP3 was greater than 1 in 62% of cases in tumor-infiltrating immune cells and 34% of cases in stromal immune cells. Our current study is the largest to assess expression of PD-L1 in a clinically well-annotated North American cohort of penile SCC. Our findings support a rationale for targeting immune-checkpoint inhibitor pathways in advanced penile SCC. PMID- 27663087 TI - Single incision laparoscopic cholecystectomy in geriatric patients. AB - BACKGROUND: Laparoscopy is a surgical approach recommended for the treatment of gall bladder disease. It is recommended also in geriatric patients. Recently Single Incision Laparoscopic Cholecystectomy (SILC) has been proposed to minimize surgical trauma, recovery and hospitalization time. However, the results and advantages of SILC in the geriatric population have received minimal attention. This case series review is focused on the results of SILC in the geriatric population. METHODS: The records of 355 patients who had undergone SILC were reviewed. This report identifies, in the entire cohort, 40 patients aged 65 years or older at the time of surgery who will be the object of this study (geriatric series). Clinical outcomes and results were evaluated. Moreover, post-operative pain of the geriatric cohort was compared to that of the entire series. RESULTS: SILC was successfully completed for 347 out of 355 patients of the entire series, with no mortality reported. In total SILC was converted to standard laparoscopy in 10 patients (2.2%) but never to open procedure. No significant difference was found between the total cohort and the geriatric series in terms of median time of operation (61.20 min vs 68.38 min). Post-operative pain was significantly lower in geriatric patients. CONCLUSION: SILC is an effective and safe procedure for the treatment of gallbladder disease of elderly, also in terms of post operative pain and it represents an alternative to the standard laparoscopic approach on a routine basis. PMID- 27663091 TI - Diversity of small, single-stranded DNA viruses of invertebrates and their chaotic evolutionary past. AB - A wide spectrum of invertebrates is susceptible to various single-stranded DNA viruses. Their relative simplicity of replication and dependence on actively dividing cells makes them highly pathogenic for many invertebrates (Hexapoda, Decapoda, etc.). We present their taxonomical classification and describe the evolutionary relationships between various groups of invertebrate-infecting viruses, their high degree of recombination, and their relationship to viruses infecting mammals or other vertebrates. They share characteristics of the viruses within the various families, including structure of the virus particle, genome properties, and gene expression strategy. PMID- 27663089 TI - Free microRNA levels in plasma distinguish T-cell mediated rejection from stable graft function after kidney transplantation. AB - The potential diagnostic value of circulating free miRNAs in plasma compared to miRNA expression in blood cells for rejection processes after kidney transplantation is largely unknown, but offers the potential for better and timely diagnosis of acute rejection. Free microRNA expression of specific blood cell markers was measured in 160 plasma samples from kidney transplant patients under standard immunosuppressive therapy (steroids+/-mycophenolic acid+/ calcineurin inhibitor) with stable graft function, urinary tract infection, interstitial fibrosis and tubular atrophy, antibody-mediated rejection (ABMR), Borderline (Banff3), tubulo-interstitial (Banff4-I) and vascular rejection (Banff4-II/III) applying RT-PCR. The expression levels of specific microRNAs miR 15B, miR-103A and miR-106A discriminated patients with stable graft function significantly (p-values 0.001996, 0.0054 and 0.0019 resp.) from patients with T cell mediated rejection (TCMR) and from patients with urinary tract infection (p values 0.0001, <0.0001 and 0.0001, resp.). A combined measurement of several microRNAs after multivariate logistic regression improved the diagnostic value supported by subsequent cross-validation. In conclusion, the measurement of circulating microRNAs in plasma from patients with renal transplants distinguishes TCMR and urinary tract infection from stable graft function. In contrast to miRNA expression measurement in blood cells it does not allow a discrimination from ABMR or interstitial fibrosis and tubular atrophy. PMID- 27663090 TI - ABO incompatible renal transplantation following lung transplantation. AB - We present management strategies utilised for the first case of an urgent live donor ABO incompatible B blood group renal transplant, in a patient with a prior A blood group lung transplant for cystic fibrosis. Three years on, renal function is excellent and stable, whilst lung function has improved. PMID- 27663092 TI - Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: An umbrella review of meta-analyses. AB - BACKGROUND: Skin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. OBJECTIVE: The present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence. METHODS: We searched PubMed up to January 20, 2016 to identify systematic reviews and meta-analyses of observational studies that examined associations between non-genetic factors and skin cancers. For each meta-analysis, we estimated the summary effect size by random-effects and fixed effects models, the 95% confidence interval and the 95% prediction interval. We also assessed the between-study heterogeneity (I2 metric), evidence for small study effects and excess significance bias. RESULTS: Forty-four eligible papers were identified and included a total of 85 associations. Twenty-one associations were significant at P<10-6. Fifty-two associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in fifteen and thirteen associations, respectively. Overall, thirteen associations (actinic keratosis, serum vitamin D, sunburns, and hair color for basal cell carcinoma and density of freckles, eye color, hair color, history of melanoma, skin type, sunburns, premalignant skin lesions, common and atypical nevi for melanoma) presented high level of credibility. CONCLUSION: The majority of meta-analyses on non-genetic risk factors for skin cancers suffered from large between-study heterogeneity and small-study effects or excess significance bias. The associations with convincing and highly suggestive evidence were mainly focused on skin photosensitivity and phenotypic characteristics. PMID- 27663093 TI - Exogenous sample contamination. Sources and interference. AB - Clinical laboratory medicine is involved in the vast majority of patient care pathways. It has been estimated that pathology results inform 60-70% of critical patient care decisions. The primary goal of the laboratory is to produce precise and accurate results which reflect the true situation in vivo. It is not surprising that interference occurs in laboratory analysis given the complexity of some of the assays used to perform them. Interference is defined as "the effect of a substance upon any step in the determination of the concentration or catalytic activity of the metabolite". Exogenous interferences are defined as those that derive from outside of the body and are therefore not normally found in a specimen and can cause either a positive or negative bias in analytical results. Interferences in analysis can come from various sources and can be classified as endogenous or exogenous. Exogenous substances could be introduced at any point in the sample journey. The laboratory must take responsibility for the quality of results produced. It has a responsibility to have processes in place to identify and minimise the occurrence and effect contamination and interference. To do this well the laboratory needs to work with clinicians and manufacturers. Failure to identify an erroneous result could have an impact on patient care, patient safety and also on hospital budgets. However it is not always easy to recognise interferences. This review summarises the types and sources of exogenous interference and some steps to minimise the impact they have. PMID- 27663094 TI - A new 'golden age' for the antitubercular target InhA. AB - The increasing prevalence of multidrug-resistant strains of Mycobacterium tuberculosis is the main contributing factor in unfavorable outcomes in the treatment of tuberculosis. Studies suggest that direct inhibitors of InhA, an enoyl-ACP-reductase, might yield promising clinical candidates that can be developed into new antitubercular drugs. In this review, we describe the application of different hit-identification strategies to InhA, which clearly illustrate the druggability of its active site through distinct binding mechanisms. We further characterize four classes of InhA inhibitors that show novel binding modes, and provide evidence of their successful target engagement as well as their in vivo activity. PMID- 27663095 TI - Study of tonotopic brain changes with functional MRI and FDG-PET in a patient with unilateral objective cochlear tinnitus. AB - We studied possible brain changes with functional MRI (fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a rare, high-intensity "objective tinnitus" (high-level SOAEs) in the left ear of 10 years duration, with no associated hearing loss. This is the first case of objective cochlear tinnitus to be investigated with functional neuroimaging. The objective cochlear tinnitus was measured by Spontaneous Otoacoustic Emissions (SOAE) equipment (frequency 9689 Hz, intensity 57 dB SPL) and is clearly audible to anyone standing near the patient. Functional modifications in primary auditory areas and other brain regions were evaluated using 3T and 7T fMRI and FDG-PET. In the fMRI evaluations, a saturation of the auditory cortex at the tinnitus frequency was observed, but the global cortical tonotopic organization remained intact when compared to the results of fMRI of healthy subjects. The FDG-PET showed no evidence of an increase or decrease of activity in the auditory cortices or in the limbic system as compared to normal subjects. In this patient with high-intensity objective cochlear tinnitus, fMRI and FDG-PET showed no significant brain reorganization in auditory areas and/or in the limbic system, as reported in the literature in patients with chronic subjective tinnitus. PMID- 27663096 TI - Anxiety in Youth With Type 1 Diabetes. AB - PROBLEM: Mental health conditions are prevalent in youth with type 1 diabetes (T1D). Anxiety symptoms and depressive symptoms are highly correlated and are two of the most prevalent mental health conditions in youth in the general population. The detrimental effect of depressive symptoms in youth with T1D has been well documented, but the effects of anxiety symptoms are not well understood. ELIGIBILITY CRITERIA: Studies were included if they were published between 1990 and 2015, and evaluated anxiety symptoms in a population of youth with T1D. SAMPLE: A total of 20 studies were identified from a sample of 338 papers. RESULTS: Anxiety symptoms were prevalent in youth with T1D. Anxiety symptoms were associated with higher glycosylated hemoglobin (HbA1c) levels, poorer self-management and coping behaviors, depressive symptoms, fear of hypoglycemia, and lower blood glucose monitoring frequency. State anxiety and trait anxiety symptoms affected health outcomes differently. Girls were at a higher risk of anxiety symptoms than boys. CONCLUSIONS: Anxiety symptoms in youth with T1D have detrimental effects on health outcomes, including self-management, quality of life, and HbA1c. IMPLICATIONS: Future research should aim to improve our current screening and treatment practices. PMID- 27663097 TI - [Standardisation and validation of an HPLC method for determining serum posaconazole levels in Colombia]. AB - BACKGROUND: Colombia currently does not have a specialised service for measuring antifungal levels in serum, which is of prime importance for the proper treatment and correct management of invasive fungal infections. AIMS: To standardise and validate a simple, sensitive, and specific protocol, based on high performance liquid chromatography, complying with the parameters recommended by the Food and Drug Administration, to detect, identify, and quantify serum concentrations of posaconazole. METHODS: A high performance liquid chromatography Agilent series-1 200 equipment was used with ultraviolet diode array detector and analytical column-Eclipse XDB-C18. Posaconazole-SCH56592 (batch IRQ-PAZ-10-X-103) was used as the primary control and itraconazole (batch ZR051211PUC921) was used as an internal control. The validation was performed taking into account all criteria recommended by the Food and Drug Administration (selectivity, calibration curves, recovery, accuracy, precision, sensitivity, reproducibility, and stability of the sample). RESULTS: The most suitable chromatographic conditions were the following: column temperature 25 degrees C, ultraviolet detection at 261nm, 50MUl injection volume, flow volume 0.8ml/min, 10min running time, mobile phase of acetonitrile:water (70:30), and final retention times of 3.4 and 7.2min for posaconazole and itraconazole, respectively, with a wide and reliable quantification range (0.125MUg/ml to 16MUg/ml). Using these parameters, the method was selective, R2 in the calibration curves was>=0.99, and the percentage recovery was 98.7%, with a coefficient of variation less than 10%. The relative error for accuracy and the coefficient of variation for precision were less than 15%, all meeting the acceptance criteria recommended by the Food and Drug Administration. CONCLUSIONS: The selectivity and chromatographic purity of the obtained signal, as well as the standardised limits of detection and quantification, make this method an excellent tool for therapeutic monitoring of patients treated with posaconazole. PMID- 27663099 TI - Response: Proposing and Meeting the Need for Interdisciplinary Cardio-Oncology Subspecialty Training by Sherry-Ann Brown, MD, PhD and Nicole Sandhu, MD, PhD. PMID- 27663098 TI - Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure. AB - BACKGROUND: Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. METHODS AND RESULTS: The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131I-Hippuran and 125I iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. CONCLUSIONS: In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. PMID- 27663101 TI - [The quest for immunotherapy response biomarkers still goes on]. PMID- 27663100 TI - Sex-Specific Effects of Adrenergic-Induced Left Ventricular Remodeling in Spontaneously Hypertensive Rats. AB - OBJECTIVE: The aim of this work was to determine whether adrenergic-induced left ventricular (LV) dilation and eccentric remodeling in pressure-overload hypertrophy is sex specific. METHODS AND RESULTS: Chronic beta-adrenoreceptor activation was produced in male and female spontaneously hypertensive rats (SHRs) by means of daily administration of isoproterenol (ISO; 0.04 mg/kg daily) from 9 to 15 months of age. LV chamber dimensions were determined in vivo by means of echocardiography and ex vivo in isolated perfused heart preparations. The acute hemodynamic response to ISO, the degree of myocardial necrosis and apoptosis, and collagen distribution were also assessed. Female SHRs demonstrated inotropic and chronotropic responses to ISO similarly to male SHRs. Compared with control subjects (saline solution vehicle), following chronic ISO administration, LV end diastolic diameter (mm) was increased in male (ISO 7.8 +/- 0.3 vs control 6.6 +/- 0.2; P < .001) but not in female (ISO 6.3 +/- 0.2 vs control 6.2 +/- 0.2; P = .23) SHRs. Similarly, compared with control, ISO administration increased the volume intercept of the LV end-diastolic pressure-volume relation (mL) in male (ISO 0.31 +/- 0.02 vs control 0.22 +/- 0.01; P < .0001) but not in female (ISO 0.17 +/- 0.01 vs control 0.17 +/- 0.01; P = 1.00) SHRs. Relative wall thickness was also decreased in male SHRs receiving ISO but not in female SHRs receiving ISO. Chronic ISO administration increased the percentage of area covered by interstitial collagen in male but not in female SHRs. Finally, chronic adrenergic stimulation failed to influence LV chamber or myocardial systolic function in either male or female SHRs. CONCLUSIONS: Male SHRs are more susceptible to adrenergic-induced LV dilation and eccentric LV remodeling than female SHRs. These effects are associated with increased collagen deposition. In pressure overload hypertrophy, LV dilation and eccentric LV remodeling occur before LV dysfunction in male rats. PMID- 27663102 TI - Mindfulness meditation for insomnia: A meta-analysis of randomized controlled trials. AB - BACKGROUND: Insomnia is a widespread and debilitating condition that affects sleep quality and daily productivity. Although mindfulness meditation (MM) has been suggested as a potentially effective supplement to medical treatment for insomnia, no comprehensively quantitative research has been conducted in this field. Therefore, we performed a meta-analysis on the findings of related randomized controlled trials (RCTs) to evaluate the effects of MM on insomnia. METHODS: Related publications in PubMed, EMBASE, the Cochrane Library and PsycINFO were searched up to July 2015. To calculate the standardized mean differences (SMDs) and 95% confidence intervals (CIs), we used a fixed effect model when heterogeneity was negligible and a random effect model when heterogeneity was significant. RESULTS: A total of 330 participants in 6 RCTs that met the selection criteria were included in this meta-analysis. Analysis of overall effect revealed that MM significantly improved total wake time and sleep quality, but had no significant effects on sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency, total wake time, ISI, PSQI and DBAS. Subgroup analyses showed that although there were no significant differences between MM and control groups in terms of total sleep time, significant effects were found in total wake time, sleep onset latency, sleep quality, sleep efficiency, and PSQI global score (absolute value of SMD range: 0.44-1.09, all p<0.05). CONCLUSIONS: The results suggest that MM may mildly improve some sleep parameters in patients with insomnia. MM can serve as an auxiliary treatment to medication for sleep complaints. PMID- 27663103 TI - The association of work stress with somatic symptoms in Chinese working women: a large cross-sectional survey. AB - OBJECTIVE: It has been suggested that the relationship between work stress and somatic symptoms (e.g., cardiopulmonary, gastrointestinal complaints, general pain, and fatigue) is particularly pronounced in women. As evidence from China is sparse, we used a large sample of Chinese working women to test those potential associations. METHODS: Data were obtained from a cross-sectional study of 6826 working women in five urban areas in China who were free from major clinical disease. The sample was drawn from five occupations (physicians, nurses, school teachers, bank employees, and industrial workers). The Effort-Reward Imbalance Questionnaire and Patient Health Questionnaire-15 were used to measure work stress and somatic symptoms, respectively. Multivariate ordinal logistic regression was performed to analyze the associations. RESULTS: 52.6% participants reported high work stress in terms of concurrent high effort and low reward. The distribution of severity of somatic symptoms covered the full range from minimal (37.3%) and low (30.6%), to medium (19.7%) and high (12.4%). The adjusted odds ratio of somatic symptoms by high work stress was 2.45 (95% confidence interval=2.24-2.68), and all single psychosocial work factors (effort, reward, and over-commitment) exerted substantial effects on somatic symptoms (odds ratios>2.00). CONCLUSIONS: Work stress is strongly associated with somatic symptoms in Chinese working women. Future longitudinal studies and intervention studies are needed to understand and improve women's psychosocial work environment and their psychosomatic health in China and elsewhere. PMID- 27663104 TI - The walk-in clinic model improves access to psychiatry in primary care. AB - OBJECTIVE: Missed appointments decrease clinic capacity and negatively affect health outcomes. The objective of this study was to increase the proportion of filled initial psychiatry appointments in an urban, hospital-based primary care practice. METHODS: Patients were identified as having a high or low risk of missing their initial psychiatry appointments based on prior missed medical appointments. High-risk patients were referred to a walk-in clinic instead of a scheduled appointment. The primary outcome was ratio of filled appointments to booked appointments. We used a statistical process control chart (p chart) to measure improvement. Secondary outcomes were percentages of patients from historically underserved groups who received an initial psychiatry evaluation before and after the intervention. RESULTS: The average ratio of filled to booked initial appointments increased from 59% to 77% after the intervention, and the p chart confirmed that this change represented special cause variation. No statistically significant demographic differences between the patients who received psychiatric evaluations before and after the intervention were found. CONCLUSIONS: Missed initial psychiatry appointments can be accurately predicted by prior missed medical appointments. A referral-based walk-in clinic is feasible and does not reduce access to care for historically underserved patient groups. PMID- 27663105 TI - Number of teeth predict depressive symptoms in a longitudinal study on patients with periodontal disease. AB - OBJECTIVE: Periodontal disease is associated with a wide range of psychosocial risk-factors. Disease-related tooth-loss has been associated with an increase in depressive symptoms in cross-sectional studies. However, while depression is a known risk-factor for the outcome of chronic diseases, it remains unclear if tooth loss can also predict depressive symptoms over the course of treatment. Aim of the current pilot study was to test, to what extend the number of teeth predict depressive symptoms several years later. METHODS: Tooth status of 310 patients with chronic and aggressive periodontitis was evaluated at the beginning of a specialized, university based outpatient treatment. We assessed depressive symptoms with the Patient Heath Questionnaire (PHQ) on average 13years later. Regression analyses were used to relate initial number of teeth to self-reported depression scores. RESULTS: Fewer teeth at the beginning of the treatment were related to higher scores of depressive symptoms, even when controlling for several covariates. CONCLUSIONS: Tooth loss is a potential risk-factor for the development of depression in periodontal disease. Further longitudinal studies that control for initial depressive symptoms are needed to identify disease mechanisms. PMID- 27663106 TI - Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis. AB - PURPOSE: Although the predictive value of vagal nerve activity, indexed by heart rate variability (HRV), has been confirmed in a variety of diseases, its value in the prediction of survival in cancer patients still remains controversial. The aim of this meta-analysis was to evaluate the predictive value of HRV in cancer patients in an evidence based manner. METHODS: A systematic review and meta analysis was conducted through a comprehensive search of the PubMed, EMBASE and the Cochrane Central Library databases for all studies regarding HRV, vagal nerve activity and cancer. Pooled data of overall survival was analyzed. RESULTS: Six studies with 1286 patients were included in our meta analysis. Analysis of the pooled data revealed that overall survival was significantly longer in the higher HRV group than in the lower HRV group (HR 0.70, 95% CI [0.60, 0.82]; P<0.001, I2=27%). CONCLUSION: The current evidence indicates a predictive value of HRV in the survival of patients with cancer and higher vagal nerve activity might predict longer survival, but the results should be applied with caution considering the heterogeneity between included studies. PMID- 27663107 TI - The association between personality traits, cognitive reactivity and body mass index is dependent on depressive and/or anxiety status. AB - OBJECTIVE: A range of biological, social and psychological factors, including depression and anxiety disorders, is thought to be associated with higher body mass index (BMI). Depression and anxiety disorders are associated with specific psychological vulnerabilities, like personality traits and cognitive reactivity, that may also be associated with BMI. The relationship between those psychological vulnerabilities and BMI is possibly different in people with and without depression and anxiety disorders. Therefore, we examined the relationship between personality traits, cognitive reactivity and severity of affective symptoms with BMI in people with and without depression and anxiety disorders. METHODS: Data from 1249 patients with current major depressive and/or anxiety disorder and 631 healthy controls were sourced from the Netherlands Study of Depression and Anxiety. Linear and logistic regression analyses were used to determine the associations between personality traits (neuroticism, extraversion, conscientiousness), cognitive reactivity (hopelessness, aggression, rumination, anxiety sensitivity), depression and anxiety symptoms with BMI classes (normal: 18.5-24.9, overweight: 25-29.9, and obese: >=30kg/m(2)) and continuous BMI. Due to significant statistical interaction, analyses were stratified for healthy individuals and depressed/anxious patients. RESULTS: Personality traits were not consistently related to BMI. In patients, higher hopelessness and aggression reactivity and higher depression and anxiety symptoms were associated with higher BMI. In contrast, in healthy individuals lower scores on hopelessness, rumination, aggression reactivity and anxiety sensitivity were associated with higher BMI. CONCLUSION: These results suggest that, particularly in people with psychopathology, cognitive reactivity may contribute to obesity. PMID- 27663108 TI - The association of unipolar depression with thirty-day mortality after hospitalization for infection: A population-based cohort study in Denmark. AB - OBJECTIVE: While depression is associated with higher risk of death due to chronic medical conditions, it is unknown if depression increases mortality following serious infections. We sought to determine if pre-existing unipolar depression is associated with increased mortality within 30days after hospitalization for a serious infection. METHODS: We conducted a population-based cohort study of all adults hospitalized for an infection in Denmark between 2005 and 2013. Pre-existing unipolar depression was ascertained via psychiatrist diagnoses or at least two antidepressant prescription redemptions within a six month period. Our primary outcome was all-cause mortality within 30days after infection-related hospitalization. We also studied death due to infection within 30days after admission. RESULTS: We identified 589,688 individuals who had a total of 703,158 hospitalizations for infections. After adjusting for demographics, infectious diagnosis and time since infection, socioeconomic factors and comorbidities, pre-existing unipolar depression was associated with slightly increased risk of all-cause mortality within 30days after infection related hospitalization (Mortality Rate Ratio [MRR]: 1.07, 95% Confidence Interval [95% CI]: 1.05, 1.09). The association was strongest among persons who initiated antidepressant treatment within one year before the infection (MRR: 1.30, 95% CI: 1.25, 1.35). Pre-existing unipolar depression was associated with increased risk of death due to sepsis (MRR: 1.30, 95% CI: 1.17, 1.44), pneumonia (MRR: 1.23, 95% CI: 1.16, 1.29) and urinary tract infection (MRR: 1.25, 95% CI: 1.08, 1.44) after adjusting for demographics, infectious diagnosis at admission and time since infection. CONCLUSIONS: Pre-existing unipolar depression is associated with slightly increased mortality following hospitalization for an infection. PMID- 27663109 TI - Psychosocial outcomes and counselee satisfaction following genetic counseling for hereditary breast and ovarian cancer: A patient-reported outcome study. AB - OBJECTIVE: We investigated the psychosocial consequences of genetic counseling and testing (GCT) for hereditary breast and ovarian cancer (HBOC) at follow-up in a "real-life" sample of counselees at an Austrian tertiary care center. METHODS: The study cohort included counselees who had undergone genetic counseling for HBOC and completed a follow-up self-report questionnaire battery on psychosocial outcomes (quality of life, psychological distress, satisfaction with counseling and decisions). For comparison of distress, we recruited a reference sample of breast cancer survivors (BCS; n=665) who had not requested GCT in the same setting. RESULTS: Overall, counselees did not exhibit increased levels of anxiety and depression when compared to BCS. No specific follow-up deleterious psychosocial consequences were detected among the former group. Of the 137 counselees, 22.6% and 9.8% experienced clinically relevant levels of anxiety and depression, respectively, at an average follow-up time of 1.8years. However, both anxiety and depression significantly decreased with time and were alike between counselees with and without cancer diagnosis. Follow-up cancer worry seems to be significantly higher among counselees who had not undergone genetic testing or were undecided about it than among counselees who had been tested. CONCLUSION: Our results strongly support GCT as part of routine care for patients with HBOC. The risk factors of increased distress in specific subgroups of counselees, such as recent cancer diagnosis or uncertainty about testing, warrant further exploration and specific attention in clinical routines. Particularly, the psychological needs of undecided counselees warrant ongoing attention and potential follow-ups. PMID- 27663110 TI - Avoidance in hypochondriasis. AB - The DSM-5 diagnosis of illness anxiety disorder adds avoidance as a component of a behavioral response to illness fears - one that was not present in prior DSM criteria of hypochondriasis. However, maladaptive avoidance as a necessary or useful criterion has yet to be empirically supported. METHODS: 195 individuals meeting DSM-IV criteria for hypochondriasis based on structured interview completed a variety of self-report and clinician-administered assessments. Data on maladaptive avoidance were obtained using the six-item subscale of the clinician-administered Hypochondriasis - Yale Brown Obsessive Compulsive Scale - Modified. To determine if avoidance emerged as a useful indicator in hypochondriasis, we compared the relative fit of continuous latent trait, categorical latent class, and hybrid factor mixture models. RESULTS: A two-class factor mixture model fit the data best, with Class 1 (n=147) exhibiting a greater level of severity of avoidance than Class 2 (n=48). The more severely avoidant group was found to have higher levels of hypochondriacal symptom severity, functional impairment, and anxiety, as well as lower quality of life. CONCLUSION: These results suggest that avoidance may be a valid behavioral construct and a useful component of the new diagnostic criteria of illness anxiety in the DSM-5, with implications for somatic symptom disorder. PMID- 27663111 TI - Mental disorder in limb reconstruction: Prevalence, associations and impact on work disability. AB - OBJECTIVE: This cross-sectional survey aimed to assess the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), and drug and alcohol dependence in a limb reconstruction population and examine associations with demographic and functional variables. METHODS: As part of routine clinical care, data were collected from 566 patients attending a tertiary referral centre for limb reconstruction between April 2012 and February 2016. Depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug dependence were measured using standardised self-report screening tools. RESULTS: 173 patients (30.6% CI 26.7-34.4) screened positive for at least one of the mental disorders assessed. 110 (19.4% CI 16.2-22.7) met criteria for probable major depression; 112 (19.9% CI 16.6-23.2) patients met criteria for probable generalised anxiety disorder; and 41 (7.6% CI 5.3-9.8) patients met criteria for probable PTSD. The prevalence of probable alcohol dependence and probable drug dependence was 1.6% (CI 0.6-2.7) and 4.5% (CI 2.7-6.3), respectively. Patients who screened positive for depression, anxiety and PTSD reported significantly higher levels of pain, fatigue, and functional impairment. Depression and anxiety were independently associated with work disability after adjustment for covariates (OR 1.98 (CI 1.08 3.62) and OR 1.83 (CI 1.04-3.23), respectively). CONCLUSION: The high prevalence and adverse associations of probable mental disorder in limb reconstruction attest to the need for routine psychological assessment and support. Integrated screening and management of mental disorder in this population may have a positive impact on patients' emotional, physical and occupational rehabilitation. A randomised controlled trial is needed to test this hypothesis. PMID- 27663112 TI - Keeping a healthy distance: Self-differentiation and perceived health among ex prisoners-of-war's wives. AB - OBJECTIVE: War captivity may affect spouses of former-prisoners-of-war (ex-POWs) in many ways, including posttraumatic stress symptoms (PTSS) and somatic difficulties manifested in negative perceived health. This is generally known as secondary traumatization. Theory suggests that development of secondary traumatization occurs through the relationship with the primary trauma survivor Figley (1986) , thus implying that the ability to keep balanced emotional distance in the relationship may play a pivotal role. Notwithstanding, the contribution of self-differentiation to secondary somatic disturbances remains largely uninvestigated. The current study fills this gap. METHODS: Ex-POWs' wives (n=143) and control former-combatants' wives (n=102), were assessed prospectively 30 (T1) and 38 (T2) years after the 1973 Yom Kippur War. Self-differentiation and PTSS were assessed at both time-points, while perceived health measures were assessed at T2. RESULTS: Wives of ex-POWs endorsed higher PTSS, lower self differentiation and negative perceived health, compared to control wives. Indirect exposure to war captivity was related to low self-differentiation and elevated PTSS, which predicted negative perceived health. Furthermore, self differentiation characterized by fusion-with-others fully mediated the relation between indirect exposure to war captivity and perceived health, beyond the effects of PTSS as a mechanism. CONCLUSION: Results suggest that tendencies towards fusion-with-others within the marital relationship, act as a risk factor not only for psychological distress but also for somatic distress among secondary trauma survivors. Hence, clinical interventions may seek to improve indirect trauma survivor's self-differentiation capacities, thus potentially facilitating the prevention of secondary somatic distress. PMID- 27663113 TI - Correlates and outcomes of worries about hypoglycemia in family members of adults with diabetes: The second Diabetes Attitudes, Wishes and Needs (DAWN2) study. AB - OBJECTIVE: We examined (a) the demographic and clinical correlates of worries about hypoglycemia in adult family members of adults with diabetes, and (b) the association of these worries with measures of diabetes support. METHODS: The second multinational Diabetes Attitudes, Wishes and Needs (DAWN2) study cross sectionally surveyed 2057 family members from 17 countries. Participants completed questions about demographics, diabetes, and psychosocial functioning, including worry about overall and nocturnal hypoglycemia. Analyses included hierarchical ordinal and linear regression. RESULTS: Eighty-five percent of family members (n=1661) were at least occasionally very worried about the risk of hypoglycemic events overall. Correlates of worries about hypoglycemia included female gender, higher age and lower education in the family member, younger age of the person with diabetes and this person being a parent or another adult (versus spouse or partner), insulin or non-insulin injectable treatment, severe or non-severe hypoglycemia in the past 12months, and family member recognition of hypoglycemia. Elevated worries about hypoglycemia had a significant independent association with increased odds of diabetes-related family arguments and family member frustration in providing helpful support (OR range 1.60-3.72). High levels of worries about hypoglycemia were associated with increased odds of attending diabetes-related health-care visits. Worries about hypoglycemia were not associated with family member involvement in diabetes care. Similar results were found for worries about nocturnal events. CONCLUSION: Worries about hypoglycemia were common in family members and were associated with suboptimal diabetes support. This issue therefore deserves increased clinician attention. PMID- 27663114 TI - Examining internet-delivered cognitive behaviour therapy for patients with chronic kidney disease on haemodialysis: A feasibility open trial. AB - OBJECTIVE: Treating depression among patients with chronic kidney disease (CKD) is imperative because of its high prevalence and health-related costs. However, many patients with CKD experience significant barriers to effective face-to-face psychological treatments. Internet-delivered cognitive behaviour therapy (iCBT) may help overcome the treatment barriers. The aim of the present study was to explore the acceptability and preliminary efficacy of iCBT for depression and anxiety among patients with CKD on haemodialysis. METHODS: A single-group open trial design involving 22 patients on dialysis and an established iCBT treatment for anxiety and depression was employed. The primary outcomes were symptoms of depression, anxiety and general psychological distress. The secondary and tertiary outcomes were disability, quality of life, kidney disease-related loss and kidney disease burden. A generalised estimation equation modelling technique was employed. RESULTS: Clinically significant improvements (avg. % of improvement) were observed in the primary outcomes of depression (34%), anxiety (31%) and general distress (26%), which were maintained or further improved to 3 month follow-up. Improvements were also observed for quality of life (12%) and kidney disease-related loss (30%). However, no improvements in disability and kidney disease burden were found. High levels of acceptability were reported and relatively little clinician time (99.45min; SD=14.61) was needed to provide the treatment. CONCLUSION: The present results provide encouraging support for the potential of iCBT as an innovative way of increasing access to effective psychological treatment for CKD patients. These results provide much needed support for further research in this area. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12613000103763. PMID- 27663115 TI - Prediabetes, depressive and anxiety symptoms, and risk of type 2 diabetes: A community-based cohort study. AB - OBJECTIVE: To examine the potential synergistic associations between prediabetes, depressive and anxiety symptoms, and the risk of incident type 2 diabetes. METHODS: Data were from the Emotional Well-Being, Metabolic Factors and Health Status (EMHS) study and included 2486 adults between 40 and 69years without diabetes at baseline. Hemoglobin A1c levels and measures of depressive and anxiety symptoms were collected at baseline and mutually exclusive groups were formed based on the presence/absence of prediabetes and high/low depressive and anxiety symptoms. A follow-up telephone interview conducted approximately 4.6years later inquired about new diabetes diagnoses. RESULTS: 86 participants developed diabetes during the follow-up period. After accounting for sociodemographic, lifestyle, and metabolic characteristics, participants with prediabetes and elevated depressive symptoms had an increased risk of developing diabetes compared to those without prediabetes and with low depressive symptoms (OR=10.65, 95% CI=4.60, 24.66). The joint effect of prediabetes and depressive symptoms on diabetes risk was synergistic (Synergy Index=2.57, 95% CI=1.02, 6.49). Similar results were found for participants with prediabetes and high symptoms of anxiety (OR=8.95, 95% CI=3.54, 22.63), however the joint effect of prediabetes and anxiety symptoms did not significantly exceed additive risk after adjusting for covariates (Synergy Index=2.39, 95% CI=0.83, 6.87). CONCLUSION: The combination of prediabetes and depressive or anxiety symptoms was associated with an increased risk of developing diabetes. This study underscores the importance of mental health in the progression from prediabetes to type 2 diabetes. PMID- 27663116 TI - Comparison of factor structure models for the Beck Anxiety Inventory among cardiac rehabilitation patients. AB - OBJECTIVE: Individuals with cardiovascular disease (CVD) experience greater rates of distress symptoms, such as anxiety and depressive symptoms, than the general population. These psychological outcomes have been linked to greater risk for negative outcomes following a cardiac event; however, research examining the relationship between specific components of anxiety and outcomes in CVD is limited. Further, prior research has not investigated the structure of anxiety symptoms in CVD. This study sought to compare previously established one, two, and four-factor models of the Beck Anxiety Inventory (BAI) in individuals enrolled in cardiac rehabilitation (CR). METHODS: Our sample included 208 individuals with CVD recruited during enrollment in a phase II CR program. Participants completed the BAI at enrollment in CR (Time 1) and again 12weeks later at CR completion (Time 2, n=151). RESULTS: Consistent with prior literature, 41% of our sample reported at least mild symptoms of anxiety (BAI>8), and the BAI proved to be a reliable measure within this sample (alpha=0.89). Confirmatory factor analysis (CFA) results indicated that a second-order model with four first order factors, consisting of cognitive, autonomic, neuromotor, and panic components, fit our data well. A multi-group CFA approach supported measurement invariance across time. CONCLUSION: These results suggest that anxiety following CVD can be evaluated based on cognitive, autonomic, neuromotor, and panic components as well as the encompassing anxiety construct. PMID- 27663117 TI - Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring. AB - OBJECTIVE: The aim of this study was to examine the association between maternal serum vitamin D status in first trimester and risk of ASD at age 3-7years in the offspring. METHODS: Using a case-control design, 68 children diagnosed with ASD and 68 sex and age matched typically-developing children were included. Archived maternal blood samples from the first trimester of pregnancy (11-13weeks gestational age) were identified for those participants. Maternal serum levels of 25 hydroxyvitamin D3 [25(OH) D], unmetabolized folic acid (FA), vitamin B12, homocysteine (HCY) and High Sensitivity C Reactive protein (CRP) were measured from those samples. We examined the associations between those factors in pregnancy and diagnosis of ASD with logistic regression using SPSS. RESULTS: Mothers in autistic group had significantly lower maternal serum levels of 25(OH) D than in typically-developing group [19.2(IQR: 15.8-22.9)ng/ml vs. 24.3(19.3 27.3)ng/ml, P<0.001], with 55.9% and 29.4% being vitamin D deficient, respectively (P<0.001). Levels of 25(OH) D increased with decreasing severity of ASD as defined by the CARS score (r=-0.302, P<0.001). Maternal first trimester serum levels of 25(OH) D in the lower 3 quartiles (quartile 1, 2, 3) (compared to the highest quartile) was associated with increased odds of ASD diagnosis in offspring [OR (95% CI) Q1: 1.36(0.84-2.58, P=0.25); Q2: 2.68(1.44-4.29, P=0.006); Q3:3.99(2.58-7.12, P<0.001)]. CONCLUSIONS: Lower first trimester maternal serum levels of 25(OH) D were associated with increased risk of developing autism in offspring. If these findings are confirmed, this may present an opportunity for prenatal intervention to reduce the risk for ASD. PMID- 27663118 TI - Transcranial magnetic stimulation as a treatment for functional (psychogenic) upper limb weakness. AB - OBJECTIVE: There has been a recent resurgence of interest in physical treatments for functional motor disorders (FMD) including Transcranial Magnetic Stimulation (TMS). This pilot study aimed to test the effectiveness of a single session of motor cortex TMS as a treatment for functional upper limb weakness. METHODS: Ten subjects with a diagnosis of functional upper limb weakness were randomised to immediate (n=7) or delayed (3months) (n=3) TMS treatment. Median age was 35 (range 23-52) and median symptom duration was 2.3years (range 5months - 20years). 46-70 single pulses were applied to the motor cortex at 120-150% motor threshold. We used a verbal protocol designed to standardized the effects of suggestion. Primary outcome measures were self-reported symptom severity, grip strength and tapping frequency immediately after treatment, and symptom severity and disability (SF-12 and Modified Rankin Scale (MRS)) after 3months. RESULTS: There was a small significant reduction in symptom severity immediately after treatment, but no improvement in grip strength or tapping frequency and no change in symptom severity, SF-12 or MRS 3months after treatment. Small numbers precluded comparison of immediate treatment with delayed treatment. Four of eight subjects responding to three-month follow-up reported late-onset adverse effects. CONCLUSION: This pilot study suggests limited benefits for TMS as a one-off non neuromodulatory treatment for stable chronic outpatients. TMS may still have a role alongside more intensive multidisciplinary therapy input, or in patients with severe deficits where the possibility of normal movement can be hard to demonstrate. TRIAL REGISTRATION: NCT02102906. PMID- 27663119 TI - Performance of administrative case definitions for depression and anxiety in inflammatory bowel disease. AB - OBJECTIVES: Comorbid depression and anxiety are common in inflammatory bowel disease (IBD), but few population-based estimates of the burden of depression and anxiety exist. Methods to support population-based studies are needed. We aimed to test the performance of administrative case definitions for depression and anxiety in IBD and to understand what the prevalence estimated using such definitions reflects. METHODS: We linked administrative (health claims) data from the province of Manitoba, Canada with clinical data for 266 persons in the Manitoba IBD Cohort Study. We compared the performance of administrative case definitions for depression and anxiety with (a) diagnoses of depression and anxiety as identified based on the Composite International Diagnostic Interview (CIDI), which identifies disorders meeting formal diagnostic criteria, and (b) participant report of physician-diagnosed depression or anxiety. RESULTS: Administrative definitions for depression showed moderate agreement with the CIDI (kappa=0.39-0.42). Agreement was higher with participant report of physician diagnosed depression (kappa=0.54). The lifetime prevalence of depression was 29.3% based on the CIDI, 17.7% based on participant report of physician-diagnosed depression, and 21.8-22.5% based on administrative data. Compared to the CIDI, administrative definitions for anxiety showed fair agreement (kappa=0.21-0.25). The lifetime prevalence of anxiety was 31.2% based on the CIDI, 9.7% based on participant report of physician-diagnosed anxiety, and 24.4-31.9% based on administrative data. CONCLUSIONS: Administrative data may be used for population level surveillance of depression and anxiety in IBD, although they will not capture undiagnosed or untreated cases. PMID- 27663120 TI - Assessing accuracy of imputation using different SNP panel densities in a multi breed sheep population. AB - BACKGROUND: Genotype imputation is a key element of the implementation of genomic selection within the New Zealand sheep industry, but many factors can influence imputation accuracy. Our objective was to provide practical directions on the implementation of imputation strategies in a multi-breed sheep population genotyped with three single nucleotide polymorphism (SNP) panels: 5K, 50K and HD (600K SNPs). RESULTS: Imputation from 5K to HD was slightly better (0.6 %) than imputation from 5K to 50K. Two-step imputation from 5K to 50K and then from 50K to HD outperformed direct imputation from 5K to HD. A slight loss in imputation accuracy was observed when a large fixed reference population was used compared to a smaller within-breed reference (including all 50K genotypes on animals from different breeds excluding those in the validation set i.e. to be imputed), but only for a few animals across all imputation scenarios from 5K to 50K. However, a major gain in imputation accuracy for a large proportion of animals (purebred and crossbred), justified the use of a fixed and large reference dataset for all situations. This study also investigated the loss in imputation accuracy specifically for SNPs located at the ends of each chromosome, and showed that only chromosome 26 had an overall imputation (5K to 50K) accuracy for 100 SNPs at each end higher than 60 % (r2). Most of the chromosomes displayed reduced imputation accuracy at least at one of their ends. Prediction of imputation accuracy based on the relatedness of low-density genotypes to those of the reference dataset, before imputation (without running an imputation software) was also investigated. FIMPUTE V2.2 outperformed BEAGLE 3.3.2 across all imputation scenarios. CONCLUSIONS: Imputation accuracy in sheep breeds can be improved by following a set of recommendations on SNP panels, software, strategies of imputation (one- or two-step imputation), and choice of the animals to be genotyped using both high- and low-density SNP panels. We present a method that predicts imputation accuracy for individual animals at the low-density level, before running imputation, which can be used to restrict genomic prediction only to the animals that can be imputed with sufficient accuracy. PMID- 27663122 TI - Preface. PMID- 27663121 TI - [Patient's preferences for repeat prescriptions in general practice]. AB - OBJECTIVE: The incidence of chronic diseases regularly increases thus focusing quality of care as a priority in chronically illness. In 2014, prescription renewal was the first reason of outpatient visit in French general practice. In fact, the follow-up of chronic disease may be somewhat longer and more complex than other standard cares. This work aimed to explore patients' preferences with regard to prescription renewal and its variation according to their own illness profiles. METHODS: Between June and July 2014, patient perceptions were collected through a self-administered questionnaire addressed to adults from 14 French GPs offices. RESULTS: In one month, 307 questionnaires were returned. More than two third patients (69.7%) evaluated the physician intervention as important as for another reason. The prescription was essential or very important for 70%. Priority points were those related to share therapeutic options with the physician and to obtain more information on their own illness. Older were more seeking for information on symptoms and disease than younger (OR=1.14 [1.03 1.23]). CONCLUSION: Patients are dealing with their own monitoring of chronic diseases. They expect more information and they look for shared decisions. The term "renewal" does not match their expectations thus leading against patient preference: we advocate substituting it to "prescription revaluation". PMID- 27663123 TI - Echocardiographic predictors of poor prognosis in congenital diaphragmatic hernia. AB - BACKGROUND/PURPOSE: The purpose of this study was to investigate echocardiographic parameters in relation to the outcomes of isolated left-sided congenital diaphragmatic hernia (CDH). METHODS: This multicenter, retrospective, observational study was conducted among patients with CDH born between 2006 and 2010. Patients in this study did not have severe cardiac malformations or chromosomal aberrations. Patients with incomplete echocardiographic examinations were excluded. In total, 84 patients with left-sided isolated CDH were included in this study. The prognostic parameters were obtained from postnatal echocardiographic images within 24h after birth. RESULTS: Eight patients died before 90days of birth. Univariate analysis showed that the presence of continuous right to left shunt at the ductus, left pulmonary artery diameter of <2.7mm, right pulmonary artery diameter of <3.3mm, and left ventricular diastolic diameter of <10.8mm, were the predictors of poor prognosis. Multivariate logistic regression analysis showed that right pulmonary artery diameter of <3.3mm (adjusted OR 10.28, 95% C.I.: 1.15-249.19) and left ventricular diastolic diameter of <10.8mm (adjusted OR 7.86, 95% C.I.: 1.01-82.82) were predictors of poor prognosis. CONCLUSIONS: This study revealed that the predictors of poor prognosis associated with CDH include smaller right pulmonary artery and left ventricular diastolic diameters. Retrospective Study-Level II. PMID- 27663124 TI - Preparing enhanced recovery after surgery for implementation in pediatric populations. AB - : Standardization in perioperative care has led to major improvements in surgical outcomes during the last two decades. Enhanced recovery after surgery (ERAS) programs are one example of a clinical pathway impacting both surgical outcomes and efficiency of care, but these programs have not yet been widely adapted for surgery in children. In adults, ERAS pathways have been shown to reduce length of stay, reduce complication rates, and improve patient satisfaction. These pathways improve outcomes through standardization of existing evidence-based best practices. Currently, the direct evidence for adapting ERAS pathways to pediatric surgery patients is limited. Challenges for implementation of ERAS programs for children include lack of direct translatability of adult evidence as well as varying levels acceptability of ERAS principles among pediatric providers and patients' families. We describe our newly implemented ERAS program for pediatric colorectal surgery patients in an era of limited direct evidence and discuss what further issues need to be addressed for broader implementation of pediatric ERAS pathways. LEVEL OF EVIDENCE: Level 5. PMID- 27663126 TI - Mild Neurocognitive Disorder: A Model for Accelerated Biological Aging? PMID- 27663125 TI - Pediatric patients with traumatic epidural hematoma at low risk for deterioration and need for surgical treatment. AB - BACKGROUND: Although some pediatric patients with small traumatic epidural hematoma (EDH) are observed without surgical drainage, clinical practice remains variable. OBJECTIVES: Create a prediction rule to identify patients with EDH unlikely to fail hospital observation. METHODS: Retrospective review at a level I pediatric trauma center between 2003 and 2014. Presenting clinical and radiographic features were compared between those successfully to failed observation. RESULTS: Two hundred twenty-two patients with EDH whose initial management strategy was observation were analyzed; 196 (88%) were successfully observed. The group failing observation was more likely to present with altered mental status (RR 18.8; 95% CI 8.7-49.6), has larger median bleed thickness (observed = 5.6mm versus failed observation = 10.9mm, p<0.01), median bleed volume (observed = 2.1ml versus failed observation = 15.7ml, p<0.01), and mass effect (RR 3.7; 95% CI 1.8-7.7). No mass effect, EDH volume<15ml, and no neurologic deficits predicted patients at low risk of failing observation with a positive predictive value of 98% (95% CI 93-99%). There was no difference in median discharge Glasgow outcome scores (5 in both groups, p=0.20). CONCLUSION: Patients with no mass effect and EDH volume <15ml on initial CT scan and no neurologic deficit are at low risk of failing observation. LEVEL OF EVIDENCE: Retrospective cohort level I. PMID- 27663127 TI - A Promising Combination Therapy for Elders. PMID- 27663128 TI - Corrections. PMID- 27663130 TI - Continuing neglect of people who inject drugs. PMID- 27663129 TI - Maternal immunisation: ethical issues. AB - There has been increased interest in the potential of maternal immunisation to protect maternal, fetal, and infant health. Maternal tetanus vaccination is part of routine antenatal care and immunisation campaigns in many countries, and it has played an important part in the reduction of maternal and neonatal tetanus. Additional vaccines that have been recommended for routine maternal immunisation include those for influenza and pertussis, and other vaccines are being developed. Maternal immunisation is controversial since regulators, professionals, and the public are often reluctant to accept pharmaceutical interventions during pregnancy. So far, little attention has been given to the ethics of vaccination during pregnancy. In this Personal View we argue that maternal immunisation should be offered in response to concrete, severe risks of disease for mother and child, and we explain how this requirement of serious risk can be used to guide ethical decision-making about maternal immunisation. PMID- 27663131 TI - Porcine reproductive and respiratory syndrome virus (PRRSV) induces IL-12p40 production through JNK-AP-1 and NF-kappaB signaling pathways. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects monocyte/macrophage cells and modulates cytokine production to regulate host immune response. IL-12p40 is the basic subunit of IL-12, a heterodimeric cytokine, which plays key roles in the cell-mediated immune response. In the present study, we demonstrated that PRRSV infection induced IL-12p40 production in vitro and in vivo. Subsequently, we showed that inhibitors of p38 MAPK, JNK, and NF-kappaB dramatically reduced PRRSV-induced IL-12p40 expression. To further characterize the molecular mechanism of IL-12p40 production induced by PRRSV infection, we cloned and analyzed the porcine IL-12p40 promoter, in which AP-1 and NF-kappaB motifs were found. In addition, both JNK-AP-1 and NF-kappaB signaling pathways were activated by PRRSV infection. Taken together, these data indicate that PRRSV induces IL-12p40 expression through the JNK-AP-1 and NF kappaB signaling pathways. Our findings might facilitate our understanding of the molecular mechanisms of IL-12 production induced by PRRSV infection. PMID- 27663132 TI - Use of focused ultrasonication in activity-based profiling of deubiquitinating enzymes in tissue. AB - To develop a reproducible tissue lysis method that retains enzyme function for activity-based protein profiling, we compared four different methods to obtain protein extracts from bovine lung tissue: focused ultrasonication, standard sonication, mortar & pestle method, and homogenization combined with standard sonication. Focused ultrasonication and mortar & pestle methods were sufficiently effective for activity-based profiling of deubiquitinases in tissue, and focused ultrasonication also had the fastest processing time. We used focused ultrasonicator for subsequent activity-based proteomic analysis of deubiquitinases to test the compatibility of this method in sample preparation for activity-based chemical proteomics. PMID- 27663133 TI - Novel Insights into PML-Dependent Oncosuppression. AB - At odds with its nuclear counterpart, extranuclear promyelocytic leukemia constitutively inhibits autophagy, hence limiting cancer progression. These data raise the interesting possibility that some tumor suppressors have become specialized to operate at multiple subcellular compartments for counteracting different aspects of the oncogenic process. PMID- 27663134 TI - Chronic but not acute immobilization stress stably enhances hippocampal CA1 metabotropic glutamate receptor dependent Long-Term Depression. AB - Acute stress has been shown to facilitate but not increase metabotropic glutamate receptor (mGluR) mediated Long-Term Depression (LTD) in the hippocampus. However, the effect of chronic stress on mGluR dependent LTD has not been investigated. Moreover, whether stress leads to a transient modification LTD threshold or a more stable change in synaptic plasticity needs to be addressed. In the present study, we have explored the effects of both a ten-day long and a single day immobilization stress protocol on mGluR-LTD at the CA3:CA1synapse in the hippocampus of adult male Sprague-Dawley rats, a day after applying stress. Bath application of the selective group 1 mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) promoted robust LTD in hippocampal slices from control (i.e. un-stressed) animals. Administration of immobility stress for two hours per day for ten days significantly elevated this LTD to a level almost twice that of control, when observed 24h following the last stress event. Acute stress i.e. a single day of two hours of immobilization, however, failed to significantly enhance LTD, 24h later. These results demonstrate for the first time, that repeated exposure to stress, but not a single stress event, is required to bring about a stable alteration in mGluR mediated synaptic plasticity. PMID- 27663135 TI - Disinhibition of neurons of the nucleus of solitary tract that project to the superior salivatory nucleus causes choroidal vasodilation: Implications for mechanisms underlying choroidal baroregulation. AB - Preganglionic neurons in the superior salivatory nucleus (SSN) that mediate parasympathetic vasodilation of choroidal blood vessels receive a major excitatory input from the baroresponsive part of the nucleus of the solitary tract (NTS). This input appears likely to mediate choroidal vasodilation during systemic hypotension, which prevents decreases in choroidal blood flow (ChBF) due to reduced perfusion pressure. It is uncertain, however, how low blood pressure signals to NTS from the aortic depressor nerve (ADN), which fires at a low rate during systemic hypotension, could yield increased firing in the NTS output to SSN. The simplest hypothesis is that SSN-projecting NTS neurons are under the inhibitory control of ADN-receptive GABAergic NTS neurons. As part of evaluating this hypothesis, we assessed if SSN-projecting NTS neurons, in fact, receive prominent inhibitory input and if blocking GABAergic modulation of them increases ChBF. We found that SSN-projecting NTS neuronal perikarya identified by retrograde labeling are densely coated with GABAergic terminals, but lightly coated with excitatory terminals. We also found that, infusion of the GABA-A receptor antagonist GABAzine into NTS increased ChBF. Our results are consistent with the possibility that low blood pressure signals from the ADN produce vasodilation in choroid by causing diminished activity in ADN-receptive NTS neurons that tonically suppress SSN-projecting NTS neurons. PMID- 27663136 TI - Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons. AB - Perampanel is an antiepileptic drug that is used to treat partial-onset seizures and generalized tonic-clonic seizures. It is a highly selective AMPA receptor allosteric antagonist. However, published data on perampanel activity vary in different studies. In the present work we studied the inhibition of native calcium-permeable and calcium-impermeable AMPA receptors in rat brain neurons by perampanel using whole-cell patch clamp technique. We found that inhibitory activity and kinetics of perampanel action do not differ between calcium permeable AMPA receptors of rat giant striatum interneurons and calcium impermeable receptors of hippocampal CA1 pyramidal neurons (the IC50 value about 60nM). Also, perampanel caused the same inhibition of steady-state currents induced by kainate and glutamate. From the other side perampanel-induced inhibition was markedly reduced in the presence of cyclothiazide (IC50 value increased to 1.2+/-0.2MUM). We demonstrated that perampanel competes with GYKI 52466 for binding site. PMID- 27663138 TI - Clean hands campaigns: 'There is no such thing as a new idea' (Mark Twain, 1906). PMID- 27663137 TI - Neuroprotective effect of mesenchymal stem cell through complement component 3 downregulation after transient focal cerebral ischemia in mice. AB - Bone marrow-derived mesenchymal stem cells (MSCs) are used in stroke treatment despite the poor understanding of its mode of action. The immune suppressive and anti-inflammatory properties of MSCs possibly play important roles in regulating neuroinflammation after stroke. We investigated whether MSCs reduce the inflammatory complement component 3 (C3) levels, thus, providing neuroprotection during stroke. Mice were subjected to transient focal cerebral ischemia (tFCI), after which MSCs were intravenously injected. The infarct volume of the brain was reduced in MSC-injected tFCI mice, and C3 expression was significantly reduced in both the brain and the blood. Additionally, the profiles of other inflammatory mediators demonstrated neuroprotective changes in the MSCs-treated group. In order to analyze the effect of MSCs on neurons during cerebral ischemia, primary cortical neurons were co-cultured with MSCs under oxygen-glucose deprivation (OGD). Primary neurons co-cultured with MSCs exhibited reduced levels of C3 expression and increased protection against OGD, indicating that treatment with MSCs reduces excessive C3 expression and rescues ischemia-induced neuronal damage. Our finding suggests that reduction of C3 expression by MSCs can help to ameliorate ischemic brain damage, offering a new neuroprotective strategy in stroke therapy. PMID- 27663139 TI - Changes in liver stiffness on real-time tissue elastography before and after occlusion of spontaneous portosystemic shunts. AB - PURPOSE: This study was conducted to evaluate changes in liver stiffness, volume, and function before and after occlusion of spontaneous portosystemic shunt. MATERIALS & METHODS: Twenty-four patients (13 men and 11 women) with a mean age of 68.2 years+/-10.1 (SD) (age range, 49-82 years) underwent percutaneous occlusion of spontaneous portosystemic shunt because of gastric varices (n=17) or hepatic encephalopathy (n=7) from March 2011 to June 2013. The liver fibrosis index indicating liver stiffness was calculated by using ultrasound elastography before and after shunt occlusion. Liver volume and liver profile were also evaluated. RESULTS: Spontaneous portosystemic shunt occlusion was uneventfully performed in all patients. The mean liver fibrosis index was significantly decreased from 2.7+/-1.0 before shunt occlusion to 2.0+/-0.9 (P<0.001) at 1 month, 2.2+/-1.0 at 3 months (P=0.004), and 1.6+/-0.7 at 6 months (P=0.001) afterwards. A significant increase in the liver volume was observed from 1035.3+/ 340.1mL before shunt occlusion to 1116.8+/-298.4mL (P=0.006) at 1 month and 1174.2+/-354.1mL (P<0.001) at 3 months afterwards. Significant improvement in the Child-Pugh score was also found at 1 month (6.2+/-1.4, P<0.001), 3 months (6.5+/ 1.1, P=0.022), and 6 months (6.0+/-0.9, P=0.004) after shunt occlusion as compared with that (7.2+/-1.9) before. CONCLUSION: The liver stiffness decreases along with an increase in liver volume and improvement in liver function after spontaneous portosystemic shunt occlusion. PMID- 27663140 TI - Selective bilateral renal artery embolization with tris-acryl microspheres in focal segmental glomerulosclerosis. PMID- 27663143 TI - Willingness of human immunodeficiency virus-positive patients to donate their organs for transplantation in Taiwan: a cross-sectional questionnaire survey. AB - BACKGROUND: With the introduction of combination antiretroviral therapy (cART) that has significantly improved survival, human immunodeficiency virus (HIV) positive patients may be potential organ donors to HIV-positive recipients in a few countries. Organ shortage remains a challenge for organ transplantation in Taiwan, where organ donation by HIV-positive patients remains prohibited by law. METHODS: We assessed the willingness of organ donation (should they be pronounced brain dead, and the ban on HIV-positive organ donation be lifted) among HIV positive patients who received regular HIV care at a university hospital in a cross-sectional survey between May and August 2015 with the use of an anonymous, self-administered questionnaire interview. RESULTS: Of the 1010 participants, 93.7% were receiving cART with the latest mean CD4 count and plasma HIV RNA load of 587 cells/mm3 and 2.73 log10 copies/mL, respectively. Overall, 71.9% were willing to donate organs. In multivariate analysis, factors associated with willingness to donate organs included college or graduate school diploma (odds ratio [OR] 1.571, 95% confidence interval [CI] 1.166-2.191), registered willingness to donate in the National Health Insurance system (OR 9.430, 95% CI 1.269-70.051), and knowledge of the information on HIV-positive deceased donors (HIVDD) (OR 1.673, 95% CI 1.073-2.608). CONCLUSIONS: We concluded that a significant proportion (71.9%) of HIV-positive Taiwanese patients were willing to donate their organs. The willingness was associated with a higher education level, prior registered willingness to donate organs, and awareness of HIVDD. PMID- 27663142 TI - RNA-binding disturbances as a continuum from spinocerebellar ataxia type 2 to Parkinson disease. AB - CAG triplet expansions in Ataxin-2 gene (ATXN2) cause spinocerebellar ataxia type 2 and have a role that remains to be clarified in Parkinson's disease (PD). To study the molecular events associated with these expansions, we sequenced them and analyzed the transcriptome from blood cells of controls and three patient groups diagnosed with spinocerebellar ataxia type 2 (herein referred to as SCA2c) or PD with or without ATXN2 triplet expansions (named SCA2p). The transcriptome profiles of these 40 patients revealed three main observations: i) a specific pattern of pathways related to cellular contacts, proliferation and differentiation associated with SCA2p group, ii) similarities between the SCA2p and sporadic PD groups in genes and pathways known to be altered in PD such as Wnt, Ephrin and Leukocyte extravasation signaling iii) RNA metabolism disturbances with "RNA-binding" and "poly(A) RNA-binding" as a common feature in all groups. Remarkably, disturbances of ALS signaling were shared between SCA2p and sporadic PD suggesting common molecular dysfunctions in PD and ALS including CACNA1, hnRNP, DDX and PABPC gene family perturbations. Interestingly, the transcriptome profiles of patients with parkinsonian phenotypes were prevalently associated with alterations of translation while SCA2c and PD patients presented perturbations of splicing. While ATXN2 RNA expression was not perturbed, its protein expression in immortalized lymphoblastoid cells was significantly decreased in SCA2c and SCA2p versus control groups assuming post-transcriptional biological perturbations. In conclusion, the transcriptome data do not exclude the role of ATXN2 mutated alleles in PD but its decrease protein expression in both SCA2c and SCA2p patients suggest a potential involvement of this gene in PD. The perturbations of "RNA-binding" and "poly(A) RNA-binding" molecular functions in the three patient groups as well as gene deregulations of factors not yet described in PD but known to be deleterious in other neurological conditions, suggest the existence of RNA-binding disturbances as a continuum between spinocerebellar ataxia type 2 and Parkinson's disease. PMID- 27663144 TI - Expression of SOX10, ABCB5 and CD271 in melanocytic lesions and correlation with survival data of patients with melanoma. AB - BACKGROUND: In malignant melanoma (MM), the proteins SOX10, ABCB5 and CD271 are strongly expressed, and are associated with tumour-initiating potential and stem cell-like properties. AIM: To compare SOX10, ABCB5 and CD271 expression profiles in melanocytic naevi and MM at different stages, and to correlate these with survival data. METHODS: Immunohistochemistry was performed for SOX10, ABCB5 and CD271 expression in common naevi (n = 14), dysplastic naevi (n = 11), primary MM (n = 39), lymph node metastases (n = 14) and distant metastases (n = 14). Data were assessed using univariate and multivariate statistics. RESULTS: Compared with melanocytic naevi, there was significantly higher SOX10 expression in primary melanomas, lymph node metastases and distant metastases. ABCB5 had significantly higher expression in primary melanomas, lymph node metastases and distant metastases compared with melanocytic naevi. CD271 expression was significantly increased in dysplatic naevi, lymph node metastases and distant metastases. Using multivariate analysis, SOX10 was demonstrated to be a significant independent positive predictor for metastatic disease. CONCLUSIONS: SOX10, ABCB5 and CD271 proteins are strongly expressed in advanced MM, whereas SOX10 appears to be the most suitable marker for independent prediction of metastatic disease. Our data indicate that SOX10, ABCB5 and CD271 might play a role in MM progression. PMID- 27663145 TI - Effectiveness of weekly azathioprine pulse in the treatment of chronic plaque psoriasis: an open-label study. AB - BACKGROUND: Azathioprine is a potent immunosuppressive drug that has been used in many immune-mediated diseases. There are a few reports of its use in psoriasis; however, azathioprine weekly pulse doses have not been evaluated in this disease. AIM: The objective of this study was to evaluate the therapeutic effectiveness of weekly oral pulse doses of azathioprine for the treatment of chronic plaque psoriasis, and to determine the side effects of this regimen both clinically and biochemically. METHODS: In this open-label clinical trial, a 300 mg bolus dose of azathioprine was given once every week orally for 24 weeks to patients with chronic plaque psoriasis having body surface area involvement of >= 10% and Psoriasis Area and Severity Index (PASI) of >= 10. Patients were evaluated every 4 weeks for 24 weeks to determine the response to treatment and any adverse effects (AEs), and then followed up for a further period of 12 weeks to determine any relapse of the disease. RESULTS: There were 50 patients in the study, of whom 28 (56%) completed the 24 weeks of treatment and 27 (54%) completed the 12-week post-treatment follow-up. Azathioprine 300 mg weekly pulse was effective in achieving PASI 75 in 42% of patients, PASI 90 in 36% of patients and PASI 100 in 22% of patients. In five patients (10%), the therapy had to be withdrawn due to AEs. CONCLUSION: Weekly azathioprine pulse appears to be an effective treatment for chronic plaque psoriasis, and can be used as an alternative therapy to other available therapeutic agents. PMID- 27663146 TI - Corticotropin-releasing hormone (CRH) and CRH receptor 1 gene expression in vitiligo. AB - BACKGROUND: Vitiligo is a disorder characterized by depigmented patches in the skin. Psychological stress can activate the hypothalamic-pituitary-adrenal axis in the brain as well as on the peripheral level and aggravate autoimmune skin diseases. Skin appendages have dual functions dually as prominent targets and sources of the peripheral corticotropin-releasing hormone (CRH) proopiomelanocortin axis. AIM: To assess the role of CRH and CRHR-1 in vitiligo, and its possible association with psychological stress. METHODS: In total, 30 patients with vitiligo and 30 healthy controls were collected from the outpatient clinic. Expression of CRH and CRHR-1 was measured by real-time PCR in lesions and control skin. RESULTS: A significant increase in CRH and CRHR-1 expression was significantly correlated with psychological stress in vitiligo. CONCLUSION: We conclude that CRH and CRHR-1 are altered by psychological stress and play an important role in the pathogenesis of vitiligo. PMID- 27663147 TI - Sweet syndrome: long-term follow-up of 138 patients. AB - BACKGROUND: Several studies support a strong association of Sweet syndrome (SS) with malignancy. However, only a few studies analysing the clinical features of malignancy-associated SS have been published in recent years. AIM: To retrospectively study the clinical features of SS that could predict the development of associated malignancies and to analyse the development of malignant neoplasia during long-term follow-up of patients with SS. METHODS: Clinical features of the patients diagnosed with SS syndrome between 1987 and 2013 at Bellvitge Hospital (Barcelona, Spain) were retrospectively analysed. RESULTS: In total, 138 patients were included in the study (66 male, 72 female, mean +/- SD age 51.24 +/- 14.11 years). SS was associated with haematological malignancy in 31 cases, infection in 23, inflammatory bowel disease in 12, inflammatory systemic disease in 8, and solid tumours in 4. It was drug-induced in 5 cases and idiopathic in 54. In four patients, an underlying haematological disease that was considered related to SS was diagnosed between 4 and 16 months after SS presentation. Variables significantly associated with malignancy in multivariate logistic regression analysis were age (OR = 1.08 for each increasing year, P = 0.01), anaemia (OR = 9.38, P = 0.001), thrombocytopenia (OR = 16.10, P < 0.01) and absence of arthralgia (OR = 11.13, P < 0.01). CONCLUSIONS: Patients with older age, anaemia or thrombocytopenia, and without arthralgia are more likely to have malignancy-associated SS. We recommend that patients with SS without clear aetiology should be followed up for at least 16 months to exclude a possible underlying haematological malignancy. PMID- 27663148 TI - Tzanck smear as an accurate and rapid diagnostic tool for cutaneous alternariosis in a renal transplant recipient. AB - Alternaria species are becoming increasingly important opportunistic pathogens in recipients of solid organ transplant, as it has been shown that dissemination with systemic involvement is not as rare as previously reported. Therefore, rapid and accurate diagnosis is necessary for appropriate patient management. We report a patient with renal transplant who developed recurrent cutaneous alternariosis. Tzanck smear successfully and very rapidly revealed hyphae and spores in both the primary and subsequent lesions. Furthermore, Tzanck smear provided guidance for histopathological examination of the second lesion, which failed to disclose the fungal elements until additional deeper serial sections were performed. The present case emphasizes that the Tzanck smear is a useful clinical tool leading to the immediate correct diagnosis even in deep fungal infections. PMID- 27663149 TI - Acral pseudolymphomatous angiokeratoma of children (APACHE)-like eruption in adult identical twins. AB - Acral pseudolymphomatous angiokeratoma of children (APACHE) is a condition that was first described in 1990 in a group of children, but has since been described in adults. We present the cases of identical twin patients aged 40 years. The first brother presented with an 8-year history of itchy lesions over the left ankle and the insteps of both feet. After a diagnostic biopsy, he was treated with potent steroids under occlusion for 8 weeks, which resulted in flattening of the lesions and resolution of the pruritus. The second twin had a 20-year history of a very similar presentation but the lesions were less pronounced; he chose not to have treatment. No other family members were affected. Skin biopsies from both patients showed similar changes. Within an overall hyperkeratotic and acanthotic epidermis, there were focal areas of lichenoid change and epidermal thinning. Beneath these areas, there was oedema and nodular aggregates of dense inflammatory cell infiltrate, predominantly lymphocytic infiltrate. APACHE has not been previously described in twins. PMID- 27663141 TI - Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target? AB - A foremost challenge for the neurons, which are among the most oxygenated cells, is the genome damage caused by chronic exposure to endogenous reactive oxygen species (ROS), formed as cellular respiratory byproducts. Strong metabolic activity associated with high transcriptional levels in these long lived post mitotic cells render them vulnerable to oxidative genome damage, including DNA strand breaks and mutagenic base lesions. There is growing evidence for the accumulation of unrepaired DNA lesions in the central nervous system (CNS) during accelerated aging and progressive neurodegeneration. Several germ line mutations in DNA repair or DNA damage response (DDR) signaling genes are uniquely manifested in the phenotype of neuronal dysfunction and are etiologically linked to many neurodegenerative disorders. Studies in our lab and elsewhere revealed that pro-oxidant metals, ROS and misfolded amyloidogenic proteins not only contribute to genome damage in CNS, but also impede their repair/DDR signaling leading to persistent damage accumulation, a common feature in sporadic neurodegeneration. Here, we have reviewed recent advances in our understanding of the etiological implications of DNA damage vs. repair imbalance, abnormal DDR signaling in triggering neurodegeneration and potential of DDR as a target for the amelioration of neurodegenerative diseases. PMID- 27663150 TI - Spiradenoma causing longitudinal splitting of the nail. AB - Longitudinal splitting of the nails can occur as a result of any growth arising in the nail matrix. We present a case of a 50-year-old woman who presented with an 18-month history of longitudinal splitting of the nail on her right little finger, along with pain in the proximal nail fold region, which was extremely tender to touch. Magnetic resonance imaging revealed an intensely enhancing lesion, while colour Doppler imaging revealed hypervascularity within the mass. A provisional diagnosis of glomus tumour was considered. Histopathology demonstrated presence of a well-circumscribed tumour comprising a dual population of cells, which stained negatively with periodic-acid-Schiff. The histopathological features were consistent with those of eccrine spiradenoma (ES). In this case, glomus tumour was considered as the first differential diagnosis, but histopathology confirmed it as an ES. PMID- 27663151 TI - Novel MBTPS2 missense mutation causes a keratosis follicularis spinulosa decalvans phenotype: mutation update and review of the literature. AB - Keratosis follicularis spinulosa decalvans (KFSD) is an X-linked condition characterized by keratotic follicular papules and progressive alopecia, which is caused by mutations in the MBTPS2 gene. We carried out a genetic study on a child who was suspected clinically to have KFSD. Sanger sequencing was performed to detect mutations in the entire coding region of MBTPS2. A novel missense mutation (c.599C>T) was identified in the patient, confirming a diagnosis of KFSD. We reviewed related cases with MBTPS2 mutations for evidence of genotype-phenotype correlations. PMID- 27663152 TI - Acrokeratosis verruciformis of Hopf exhibiting Darier disease-like cytological features. AB - The relationship between acrokeratosis verruciformis (AVH; also known as Hopf disease) and Darier disease (DD) has been debated for several decades. There is still substantial controversy over the characterization and association of AVH with DD. Certain histopathological features overlapping with those of DD have been demonstrated in patients with AVH. Although cytological findings have been described in DD, no study has identified the cytological changes in AVH. We report a case of AVH exhibiting a DD-like cytological manifestation. The samples from the most prominent lesions were examined by split-skin smear test. Cytological examination showed acantholytic keratinocytes, dyskeratotic acantholytic cells, corps ronds and grains. Histopathological examination showed compact hyperkeratosis, hypergranulosis, slight acanthosis, circumscribed epidermal elevations resembling church spires, and a cleft in the granular layer with several acantholytic cells. Our case indicates that the cytological findings of AVH are similar to those of DD. PMID- 27663153 TI - Localized axillary milia en plaque: a rare cutaneous case presentation of systemic amyloidosis. AB - Systemic AL amyloidosis is known to be associated with plasma cell dyscrasias, including multiple myeloma. The cutaneous manifestations of systemic AL amyloidosis are varied, but typically include waxy plaques or subcutaneous nodules. We report a woman who presented with bilateral eruptions of hyperpigmented plaques in her axillae, which were diagnosed as milia en plaque. She had a history of multiple myeloma, for which she was under the care of a haematologist. This is the first documented case, to our knowledge, of an eruption in the axillae being milia en plaque. PMID- 27663154 TI - Cutaneous Mycobacterium abscessus infection following hair transplant. AB - A 28-year-old man presented with a 10-day history of scalp nodules. He had undergone hair transplantation 2 months previously. Incision and drainage of one of the nodules yielded gelatinous material, which was sent for microscopy and culture, including low-temperature culture. After 2 weeks of incubation, culture of the nodule yielded acid- and alcohol-fast bacilli, which were identified as Mycobacterium abscessus, a rapidly growing, nontuberculous mycobacterium, which has been reported to cause cutaneous, soft tissue and respiratory infections following trauma, surgery or injection with nonsterile needles. A high index of suspicion is therefore needed in patients who present with cutaneous infections after cosmetic dermatological procedures, including hair transplantation. PMID- 27663155 TI - Two patients with Ehlers-Danlos syndrome type VIII with unexpected hoarseness. AB - Ehlers-Danlos syndrome (EDS) encompasses a genetically and clinically heterogeneous group of connective tissue disorders, characterized by joint hypermobility, skin hyperextensibility and tissue fragility. It is a rare condition, and inheritance is either autosomal dominant or recessive. Previously grouped into 11 different subtypes, with increasing knowledge of the underlying molecular defects, it was reclassified in 1997 into 6 major groups, with type VIII excluded from this classification. Type VIII EDS is a very rare subtype, characterized by severe, early-onset periodontitis, skin fragility and abnormal scarring. Voice abnormalities have occasionally been described in other forms of the condition, and may be due to defects in the collagen of the vocal ligament. We report two cases of patients with EDS type VIII and hoarseness. PMID- 27663156 TI - Isolated linear blaschkoid psoriasis. AB - Linear psoriasis (LPs) is considered a rare clinical presentation of psoriasis, which is characterized by linear erythematous and scaly lesions along the lines of Blaschko. We report the case of a 20-year-old man who presented with asymptomatic linear and S-shaped erythematous, scaly plaques on right side of his trunk. The plaques were arranged along the lines of Blaschko with a sharp demarcation at the midline. Histological examination of a skin biopsy confirmed the diagnosis of psoriasis. Topical calcipotriol and betamethasone dipropionate ointments were prescribed for 2 months. A good clinical improvement was achieved, with reduction in lesion thickness and scaling. In patients with linear erythematous and scaly plaques along the lines of Blaschko, the diagnosis of LPs should be kept in mind, especially in patients with asymptomatic lesions of late onset. PMID- 27663157 TI - Food allergen-mediated exacerbations of oral lichen planus. AB - Erosive oral lichen planus (OLP) is a chronic autoimmune condition of unknown aetiology, characterized by periods of exacerbation and quiescence. Many patients with OLP report triggers of flares that overlap with triggers of other oral diseases, including oral allergy syndrome (OAS), an IgE-mediated food allergy. We report a case that, to our knowledge, is the first reported case of concurrent OLP and OAS diagnoses, which provides insight into the triggers of OLP and the role of trigger avoidance. A woman in her 60s presented with erosive OLP refractory to prednisone and azathioprine. She reported that certain food exposures triggered flares of her OLP. She was subsequently diagnosed with concurrent OAS, and avoidance of food allergens resulted in a clinically significant improvement in her OLP, eventually allowing her to taper off systemic treatment altogether. Further studies are needed to pinpoint common triggers and examine the role of trigger avoidance as a management strategy for OLP. PMID- 27663158 TI - Anti-apoptotic function of herpes simplex virus -2 latency-associated transcript RL1 sequence and screening of its encoded microRNAs. AB - BACKGROUND: The latency-associated transcript (LAT) gene of herpes simplex virus (HSV)-2 is the only detectable viral gene expressed during latent infection in neurons. LAT inhibits apoptosis and maintains latency by promoting the survival of infected neurons. However, whether LAT functions during HSV-2 infection via its encoded RNAs or via its encoded proteins remain unknown. Increasing evidence has indicated that LAT is likely to functionally promote the establishment of latent infection via LAT-encoded microRNAs (miRNAs). AIM: To explore whether the RL1 fragment of the five adjacent miRNAs has an effect on cell apoptosis, then provide supporting evidence to elucidate the potential role of these miRNAs and to aid screening of their cellular targets. METHODS: A number of techniques, including MTT assay, flow cytometry and DNA ladder analysis, were used to verify the role of the RL1 fragment and the contribution of the individual miRNAs to the anti-apoptotic effect. RESULTS: Five miRNAs (miR-H3, miR-H4-3p, miR-H4-5p, miR H24 and miR-H19) were detected by quantitative PCR in PC12 cells stably expressing RL1 after pEGFP-RL1 plasmid transfection in vitro. The data indicated that expression of HSV-2 LAT RL1 seems to provide protection against apoptosis of PC12 cells induced by ActD. Antisense miRNAs specifically inhibiting these five miRNAs could efficiently reduce their expression. Transfection of antisense-miR H3, antisense-miR-H4-5p and antisense-miR-H19 into PC12 cells stably expressing RL1 were able to partly reverse the anti-apoptotic effect of these miRNAs. CONCLUSIONS: These findings indicate that the apoptotic role of the RL1 fragment is likely to be related to overexpression of miR-H3, miR-H4-5p and miR-H19 in PC12 cells. PMID- 27663159 TI - Skin photorejuvenation effects of light-emitting diodes (LEDs): a comparative study of yellow and red LEDs in vitro and in vivo. AB - BACKGROUND: Red-coloured light-emitting diodes (LEDs) can improve skin photorejuvenation and regeneration by increasing cellular metabolic activity. AIM: To evaluate the effectiveness of visible LEDs with specific wavelengths for skin photorejuvenation in vitro and in vivo. METHODS: Normal human dermal fibroblasts (HDFs) from neonatal foreskin were cultured and irradiated in vitro by LEDs at different wavelengths (410-850 nm) and doses (0-10 J/cm(2) ). In vivo experiments were performed on the skin of hairless mice. Expression of collagen (COL) and matrix metalloproteinases (MMPs) was evaluated by semi-quantitative reverse transcription PCR (semi-qRT-PCR), western blotting and a procollagen type I C-peptide enzyme immunoassay (EIA). Haematoxylin and eosin and Masson trichrome stains were performed to evaluate histological changes. RESULTS: In HDFs, COL I was upregulated and MMP-1 was downregulated in response to LED irradiation at 595 +/- 2 and 630 +/- 8 nm. In the EIA, a peak result was achieved at a dose of 5 J/cm(2) with LED at 595 +/- 2 nm. In vivo, COL I synthesis was upregulated in a dose-dependent manner to both 595 and 630 nm LED irradiation, and this effect was prolonged to 21 days after a single irradiation with a dose of 100 J/cm(2) . These histological changes were consistent with the results of semi-qRT-PCR and western blots. CONCLUSION: Specific LED treatment with 595 +/- 2 and 630 +/- 8 nm irradiation was able to modulate COL and MMPs in skin, with the effects persisting for at least 21 days after irradiation. These findings suggest that yellow and red LEDs might be useful tools for skin photorejuvenation. PMID- 27663160 TI - A sporadic case of Nagashima-type palmoplantar keratosis caused by gene mutation in SERPINB7. PMID- 27663161 TI - Novel clinical and molecular findings in Chinese families with Hailey-Hailey disease: an update. PMID- 27663162 TI - Childhood linear IgA bullous dermatosis successfully treated with oral nicotinamide. PMID- 27663163 TI - Isolation of Bacillus simplex strain from Demodex folliculorum and observations about Demodicosis spinulosa. PMID- 27663164 TI - Treatment of acquired reactive perforating collagenosis with 308-nm excimer laser. PMID- 27663165 TI - Bimatoprost in vitiligo. PMID- 27663166 TI - Multiple asymptomatic papules. PMID- 27663167 TI - Unusual ulcer in an immunocompromised host. PMID- 27663168 TI - Dry skin and blistering in childhood. PMID- 27663169 TI - An unsual cause of bilateral pigmentation on the upper back. PMID- 27663170 TI - An intensely itchy papular eruption. PMID- 27663172 TI - The contribution of unsafe blood transfusion to human immunodeficiency virus incidence in sub-Saharan Africa: reexamination of the 5% to 10% convention. AB - BACKGROUND: Historical estimates have attributed 5% to 10% of new human immunodeficiency virus (HIV) infections in sub-Saharan Africa (SSA) to unsafe blood transfusions. Although frequently cited, the validity of this statistic is uncertain or outdated. Recent estimates suggest blood transfusion's contribution to new HIV infections in the region may be much lower. STUDY DESIGN AND METHODS: We searched the peer-reviewed and gray literature for quantitative estimates of the specific contribution of unsafe blood transfusion to the proportion of new HIV infections occurring in SSA. The sources and methods used to generate attribution estimates were evaluated against published country-specific HIV prevalence data. RESULTS: Despite multiple secondary citations, a primary published source attributing 5% to 10% of new HIV infections to blood transfusions in SSA could not be established for the current era. The United Nations Programme on HIV and AIDS (UNAIDS) modes of transmission (MOT) reports representing 15 countries suggest that between 0 and 1.1% of new HIV infections per year (median, 0.2% or approx. two out of 1000 new infections each year) may be attributable to blood transfusions. CONCLUSION: Recent modeled estimates suggest that blood transfusions account for a very low proportion of new HIV infections in SSA, likely an order of magnitude lower than 5% to 10%. Direct quantification of risk is challenging given the paucity of data on the variables that impact transfusion-associated HIV. Specifically, data on HIV incidence in blood donors, blood bank laboratory test performance, and posttransfusion surveillance are lacking. Findings suggest an urgent need for improved surveillance and modeling of transfusion-associated HIV transmission in the region. PMID- 27663171 TI - Concise Review: Lessons from Naive Human Pluripotent Cells. AB - The naive state of pluripotency is actively being explored by a number of labs. There is some controversy in the field as to the true identity of naive human pluripotent cells as they are not exact mirrors of the mouse. The various reports published, although in basic agreement, present discrepancies in the characterization of the various lines, which likely reflect the etiology of these lines. The primary lesson learned from these contributions is that a human naive state reflecting the preimplantation human is likely to exist. The essential factors that will universally maintain the naive state in human cells in vitro are not yet fully understood. These first need to be identified in order to describe the definitive characteristics of this state. Comparisons of naive and primed human pluripotent cells have also highlighted consistencies between states and broadened our understanding of embryonic metabolism, epigenetic change required for development, embryonic DNA repair strategies and embryonic expression dynamics. Stem Cells 2017;35:35-41. PMID- 27663173 TI - Convergence of models of human ventricular myocyte electrophysiology after global optimization to recapitulate clinical long QT phenotypes. AB - In-silico models of human cardiac electrophysiology are now being considered for prediction of cardiotoxicity as part of the preclinical assessment phase of all new drugs. We ask the question whether any of the available models are actually fit for this purpose. We tested three models of the human ventricular action potential, the O'hara-Rudy (ORD11), the Grandi-Bers (GB10) and the Ten Tusscher (TT06) models. We extracted clinical QT data for LQTS1 and LQTS2 patients with nonsense mutations that would be predicted to cause 50% loss of function in IKs and IKr respectively. We also obtained clinical QT data for LQTS3 patients. We then used a global optimization approach to improve the existing in silico models so that they reproduced all three clinical data sets more closely. We also examined the effects of adrenergic stimulation in the different LQTS subsets. All models, in their original form, produce markedly different and unrealistic predictions of QT prolongation for LQTS1, 2 and 3. After global optimization of the maximum conductances for membrane channels, all models have similar current densities during the action potential, despite differences in kinetic properties of the channels in the different models, and more closely reproduce the prolongation of repolarization seen in all LQTS subtypes. In-silico models of cardiac electrophysiology have the potential to be tremendously useful in complementing traditional preclinical drug testing studies. However, our results demonstrate they should be carefully validated and optimized to clinical data before they can be used for this purpose. PMID- 27663175 TI - Regulating the regulator: Insights into the cardiac protein phosphatase 1 interactome. AB - Reversible phosphorylation of proteins is a delicate yet dynamic balancing act between kinases and phosphatases, the disturbance of which underlies numerous disease processes. While our understanding of protein kinases has grown tremendously over the past decades, relatively little is known regarding protein phosphatases. This may be because protein kinases are great in number and relatively specific in function, and thereby amenable to be studied in isolation, whereas protein phosphatases are much less abundant and more nonspecific in their function. To achieve subcellular localization and substrate specificity, phosphatases depend on partnering with a large number of regulatory subunits, protein scaffolds and/or other interactors. This added layer of complexity presents a significant barrier to their study, but holds the key to unexplored opportunities for novel pharmacologic intervention. In this review we focus on serine/threonine protein phosphatase type-1 (PP1), which plays an important role in cardiac physiology and pathophysiology. Although much work has been done to investigate the role of PP1 in cardiac diseases including atrial fibrillation and heart failure, most of these studies were limited to examining and manipulating the catalytic subunit(s) of PP1 without adequately considering the PP1 interactors, which give specificity to PP1's functions. To complement these studies, three unbiased methods have been developed and applied to the mapping of the PP1 interactome: bioinformatics approaches, yeast two-hybrid screens, and affinity-purification mass spectrometry. The application of these complementary methods has the potential to generate a detailed cardiac PP1 interactome, which is an important step in identifying novel and targeted pharmacological interventions. PMID- 27663174 TI - Minocycline attenuates cardiac dysfunction in tumor-burdened mice. AB - Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs are involved in remodeling remains obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern; novel therapeutics are needed to prevent cardiac complications. Minocycline is a well known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction. PMID- 27663177 TI - Effect of mahanimbine, an alkaloid from curry leaves, on high-fat diet-induced adiposity, insulin resistance, and inflammatory alterations. AB - Spices and condiments, small but an integral part of the daily diet, are known to affect physiological functions. This study evaluated the effects of mahanimbine, a major carbazole alkaloid from Murraya koenigii (curry leaves), against progression of high-fat diet (HFD)-induced metabolic complications in mice (male and female). Mahanimbine at 2 mg/kg (HFD + LD) and 4 mg/kg (HFD + HD) of body weight was administered daily along with HFD feeding for 12 weeks. At the end of the study, male HFD + LD and HFD + HD groups showed 51.70 +/- 3.59% and 47.37 +/- 3.73% weight gain, respectively, as compared with 71.02 +/- 6.04% in HFD fed mice whereas female HFD + LD and HFD + HD groups showed 24.31 +/- 1.68% and 25.10 +/- 2.61% weight gain as compared with HFD group with 36.69 +/- 3.60% of weight gain. Mahanimbine prevented HFD-induced hyperlipidemia and fat accumulation in adipose tissue and liver along with the restricted progression of systemic inflammation and oxidative stress. Moreover, mahanimbine treatment improved glucose clearance and upregulated the expression of insulin responsive genes in liver and adipose tissue. Male and female mice showed different traits in development of HFD induced metabolic disturbances; however, mahanimbine treatment exerted similar effects in both the sexes. In addition, mahanimbine lowered the absorption of dietary fat resulting in dietary fat excretion. In conclusion, daily consumption of mahanimbine and thereby curry leaves may alleviate development of HFD-induced metabolic alterations. (c) 2016 BioFactors, 43(2):220-231, 2017. PMID- 27663178 TI - ICU antimicrobial stewardship (AMS) rounds: the daily activities of an AMS service. PMID- 27663176 TI - Expression of the phosphodiesterase BifA facilitating swimming motility is partly controlled by FliA in Pseudomonas putida KT2440. AB - Flagella-mediated motility is an important capability of many bacteria to survive in nutrient-depleted and harsh environments. Decreasing the intracellular cyclic di-GMP (c-di-GMP) level by overexpression of phosphodiesterase BifA promotes flagellar-mediated motility and induces planktonic lifestyle in Pseudomonas. The mechanism that regulates expression of bifA gene was poorly studied. Here we showed that expression of BifA was partly controlled by flagellar sigma factor FliA (sigma28 ) in Pseudomonas putidaKT2440. FliA deletion led to an approximately twofold decrease in transcription of bifA. 5' race assay revealed two transcription start points in bifA promoter region, with the putative sigma70 and sigma28 promoter sequences upstream, respectively. Point mutation in sigma28 promoter region reduced transcriptional activity of the promoter in wild-type KT2440, but showed no influence on that in fliA deletion mutant. FliA overexpression decreased the intracellular c-di-GMP level in a BifA-dependent way, suggesting that FliA was able to modulate the intracellular c-di-GMP level and BifA function was required for the modulation. Besides, FliA overexpression enhanced swimming ability of wild-type strain, while made no difference to the bifA mutant. Our results suggest that FliA acts as a negative regulator to modulate the c-di-GMP level via controlling transcription of bifA to facilitate swimming motility. PMID- 27663179 TI - Clinical outcomes associated with per-operative discontinuation of aspirin in patients with coronary artery disease: A systematic review and meta-analysis. AB - BACKGROUND: Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs. late discontinuation(<3-5 days)/no discontinuation of aspirin. METHODS: Multiple databases were searched from inception of these databases until March 2015 to identify studies that reported discontinuation of aspirin in patients undergoing surgery. The outcomes measured were all cause mortality, nonfatal myocardial infarction and other relevant thrombotic events (MACE) which also may include, fatal and nonfatal MI, stent thrombosis and restenosis, stroke, perioperative cardiovascular complications (heart failure, MI, VTE, acute stroke) and perioperative bleeding during the perioperative period to up to 30 days after surgery. RESULTS: A total of 1,018 titles were screened, after which six observational studies met the inclusion criteria. Our analysis suggests that there is no difference in MACE with planned discontinuation of aspirin (OR = 1.17, 95% CI = 0.76-1.81; P = 0.05; I2 = 55%). Early discontinuation of aspirin showed a decreased risk of peri operative bleeding (OR 0.82, 95% CI = 0.67-0.99; P = 0.04; I2 = 42%). CONCLUSION: Our analysis suggests that planned short-term discontinuation in the appropriate clinical setting appears to be safe in the correct clinical setting with no increased risk of thrombotic events and with a decreased risk of bleeding. (c) 2016 Wiley Periodicals, Inc. PMID- 27663181 TI - Prediction model for mortality in cancer patients with pneumonia: comparison with CURB-65 and PSI. AB - INTRODUCTION AND OBJECTIVES: We aimed to develop a new prediction model of mortality in cancer patients with pneumonia and to compare its performance with CURB-65 and the Pneumonia Severity Index (PSI). METHODS: Active cancer patients who were diagnosed with pneumonia at the Emergency Department (ED) from 7/1/2014 to 12/31/2014 were consecutively included. Clinical data were collected through a medical chart review. The primary outcome was the 28-day mortality, and clinical factors were analyzed using logistic regression analysis. RESULTS: Among a total of 218 analyzed patients with a median age of 64.0 years (IQR, 56.8-71.0) and a male proportion of 72%, 42 (19.3%) died within 28 days of ED admission. By multivariate logistic regression analysis, an ECOG performance status (PS) 3 (OR: 8.54, 95% CI: 3.42-21.33) or 4 (OR: 13.17, 95% CI: 3.19-54.32), SpO2 <90% (OR: 3.06, 95% CI: 1.17-8.00), and elevated lactic acid levels (OR: 1.42, 95% CI: 1.12 1.81) were significantly associated with mortality. With these three variables, a new prediction model with total scores ranged from 0 to 6 was generated. The area under the curve of the new prediction model was 0.840, compared with 0.673 and 0.586 for CURB-65 and PSI, respectively. CONCLUSION: In cancer patients with pneumonia, a poor ECOG PS, SpO2 <90%, and lactic acid elevation are independent predictors of mortality. The new prediction model, comprising three predictors, performs better in predicting mortality in cancer patients than CURB-65 or PSI. PMID- 27663182 TI - Cholesterol 24-hydroxylase: Brain cholesterol metabolism and beyond. AB - Dysfunctions in brain cholesterol homeostasis have been extensively related to brain disorders. The major elimination pathway of brain cholesterol is its hydroxylation into 24 (S)-hydroxycholesterol by the cholesterol 24-hydroxylase (CYP46A1). Interestingly, there seems to be an association between CYP46A1 and high-order brain functions, in a sense that increased expression of this hydroxylase improves cognition, while a reduction leads to a poor cognitive performance. Moreover, increasing amount of epidemiological, biochemical and molecular evidence, suggests that CYP46A1 has a role in the pathogenesis or progression of neurodegenerative disorders, in which up-regulation of this enzyme is clearly beneficial. However, the mechanisms underlying these effects are poorly understood, which highlights the importance of studies that further explore the role of CYP46A1 in the central nervous system. In this review we summarize the major findings regarding CYP46A1, and highlight the several recently described pathways modulated by this enzyme from a physiological and pathological perspective, which might account for novel therapeutic strategies for neurodegenerative disorders. PMID- 27663180 TI - Clinical Predictors of Hospital Mortality Differ Between Direct and Indirect ARDS. AB - BACKGROUND: Direct (pulmonary) and indirect (extrapulmonary) ARDS are distinct syndromes with important pathophysiologic differences. The goal of this study was to determine whether clinical characteristics and predictors of mortality differ between direct or indirect ARDS. METHODS: This retrospective observational cohort study included 417 patients with ARDS. Each patient was classified as having direct (pneumonia or aspiration, n = 250) or indirect (nonpulmonary sepsis or pancreatitis, n = 167) ARDS. RESULTS: Patients with direct ARDS had higher lung injury scores (3.0 vs 2.8; P < .001), lower Simplified Acute Physiology Score II scores (51 vs 62; P < .001), lower Acute Physiology and Chronic Health Evaluation II scores (27 vs 30; P < .001), and fewer nonpulmonary organ failures (1 vs 2; P < .001) compared with patients with indirect ARDS. Hospital mortality was similar (28% vs 31%). In patients with direct ARDS, age (OR, 1.29 per 10 years; P = .01; test for interaction, P = .03), lung injury scores (OR, 2.29 per point; P = .001; test for interaction, P = .058), and number of nonpulmonary organ failures (OR, 1.67; P = .01) were independent risk factors for increased hospital mortality. Preexisting diabetes mellitus was an independent risk factor for reduced hospital mortality (OR, 0.47; P = .04; test for interaction, P = .02). In indirect ARDS, only the number of organ failures was an independent predictor of mortality (OR, 2.08; P < .001). CONCLUSIONS: Despite lower severity of illness and fewer organ failures, patients with direct ARDS had mortality rates similar to patients with indirect ARDS. Factors previously associated with mortality during ARDS were only associated with mortality in direct ARDS. These findings suggest that direct and indirect ARDS have distinct features that may differentially affect risk prediction and clinical outcomes. PMID- 27663183 TI - Lipid fingerprint image accurately conveys human colon cell pathophysiologic state: A solid candidate as biomarker. AB - Membrane lipids are gaining increasing attention in the clinical biomarker field, as they are associated with different pathologic processes such as cancer or neurodegenerative diseases. Analyzing human colonoscopic sections by matrix assisted laser/desorption ionization (MALDI) mass spectrometry imaging techniques, we identified a defined number of lipid species changing concomitant to the colonocyte differentiation and according to a quite simple mathematical expression. These species felt into two lipid families tightly associated in signaling: phosphatidylinositols and arachidonic acid-containing lipids. On the other hand, an opposed pattern was observed in lamina propria for AA-containing lipids, coinciding with the physiological distribution of the immunological response cells in this tissue. Importantly, the lipid gradient was accompanied by a gradient in expression of enzymes involved in lipid mobilization. Finally, both lipid and protein gradients were lost in adenomatous polyps. The latter allowed us to assess how different a single lipid species is handled in a pathological context depending on the cell type. The strict patterns of distribution in lipid species and lipid enzymes described here unveil the existence of fine regulatory mechanisms orchestrating the lipidome according to the physiological state of the cell. In addition, these results provide solid evidence that the cell lipid fingerprint image can be used to predict precisely the physiological and pathological status of a cell, reinforcing its translational impact in clinical research. PMID- 27663184 TI - PPARgamma regulates exocrine pancreas lipase. AB - AIM: Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARgamma), and as we identified in-silico putative PPARgamma binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARgamma. MATERIALS AND METHODS: We used in silico bioinformatics tools, reporter luciferase assay, PPARgamma agonists and antagonists, PPARgamma overexpression in exocrine pancreas AR42J and primary cells to study PPARgamma regulation of PNLIP. RESULTS: Using in silico bioinformatics tools we mapped PPARgamma binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARgamma dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARgamma agonists and reduced by PPARgamma antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARgamma significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARgamma agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARgamma antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. CONCLUSION: PPARgamma transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. PMID- 27663185 TI - Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23-IL-17 signaling in macrophages. AB - Conjugates of fatty acids and amines, including endocannabinoids, are known to play important roles as endogenous signaling molecules. Among these, the ethanolamine conjugate of the n-3 poly unsaturated long chain fatty acid (PUFA) docosahexaenoic acid (22:6n-3) (DHA) was shown to possess strong anti inflammatory properties. Previously, we identified the serotonin conjugate of DHA, docosahexaenoyl serotonin (DHA-5-HT), in intestinal tissues and showed that its levels are markedly influenced by intake of n-3 PUFAs. However, its biological roles remain to be elucidated. Here, we show that DHA-5-HT possesses potent anti-inflammatory properties by attenuating the IL-23-IL-17 signaling cascade in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Transcriptome analysis revealed that DHA-5-HT down-regulates LPS-induced genes, particularly those involved in generating a CD4+ Th17 response. Hence, levels of PGE2, IL-6, IL-1beta, and IL-23, all pivotal macrophage-produced mediators driving the activation of pathogenic Th17 cells in a concerted way, were found to be significantly suppressed by concentrations as low as 100-500nM DHA-5-HT. Furthermore, DHA-5-HT inhibited the ability of RAW264.7 cells to migrate and downregulated chemokines like MCP-1, CCL-20, and gene-expression of CCL-22 and of several metalloproteinases. Gene set enrichment analysis (GSEA) suggested negative overlap with gene sets linked to inflammatory bowel disease (IBD) and positive overlap with gene sets related to the Nrf2 pathway. The specific formation of DHA-5-HT in the gut, combined with increasing data underlining the importance of the IL-23-IL-17 signaling pathway in the etiology of many chronic inflammatory diseases merits further investigation into its potential as therapeutic compound in e.g. IBD or intestinal tumorigenesis. PMID- 27663187 TI - Event-triggered reliable control for fuzzy Markovian jump systems with mismatched membership functions. AB - The problem of event-triggered reliable control for fuzzy Markovian jump system (FMJS) with mismatched membership functions (MMFs) is addressed. Based on the mode-dependent reliable control and event-triggered communication scheme, the stability conditions and control design procedure are formulated. More precisely, a general actuator-failure is designed such that the FMJS is reliable in the sense of stochastically stable and reduce the utilization of network resources. Furthermore, the improved MMFs are introduced to reduce the conservativeness of obtained results. Finally, simulation results indicate the effectiveness of the proposed methodology. PMID- 27663188 TI - Neuro-adaptive backstepping control of SISO non-affine systems with unknown gain sign. AB - This paper presents two neuro-adaptive controllers for a class of uncertain single-input, single-output (SISO) nonlinear non-affine systems with unknown gain sign. The first approach is state feedback controller, so that a neuro-adaptive state-feedback controller is constructed based on the backstepping technique. The second approach is an observer-based controller and K-filters are designed to estimate the system states. The proposed method relaxes a priori knowledge of control gain sign and therefore by utilizing the Nussbaum-type functions this problem is addressed. In these methods, neural networks are employed to approximate the unknown nonlinear functions. The proposed adaptive control schemes guarantee that all the closed-loop signals are semi-globally uniformly ultimately bounded (SGUUB). Finally, the theoretical results are numerically verified through simulation examples. Simulation results show the effectiveness of the proposed methods. PMID- 27663186 TI - Anticholinergic Drug Burden in Noncancer Versus Cancer Patients Near the End of Life. AB - CONTEXT: Anticholinergic drugs can cause several side effects, impairing cognition and quality of life (QOL). Cancer patients are often exposed to increasing cumulative anticholinergic load (ACL) as they approach death, but this burden has not been examined in patients with nonmalignant diseases. OBJECTIVES: To determine ACL and its impact in noncancer versus cancer palliative care patients. METHODS: We performed a secondary analysis of 244 subjects enrolled in a randomized controlled trial. ACL was quantified with the Anticholinergic Drug Scale. We used multivariable regression to calculate the effect of ACL on key outcomes, including drowsiness, fatigue, and QOL. Patients were stratified by diagnosis, and drugs were grouped as symptom management (SM) or disease management (DM). RESULTS: Overall, ACL in cancer and noncancer patients was not significantly different (2.6 vs. 2.4; P = 0.23). SM drugs caused greater anticholinergic exposure than DM drugs in both cancer and noncancer patients (2.3 vs. 0.5, and 1.5 vs. 1.3, respectively; both P < 0.05); however, DM drugs exposed noncancer patients to relatively more ACL than cancer patients (1.2 vs. 0.6, P < 0.0001). ACL was associated with worse fatigue (odds ratio, 1.08; CI, 1.002-1.17) and worse QOL (odds ratio, 0.89; CI, 0.80-0.98). CONCLUSIONS: ACL is associated with worse fatigue and QOL and may not differ significantly between cancer and noncancer patients nearing end of life. SM drugs are more responsible for ACL in cancer and noncancer patients, although DM drugs contribute significantly to ACL in the latter group. We recommend more attention to reducing anticholinergic use in all patients with life-limiting illness. PMID- 27663190 TI - The Efficacy of Combined Use of Rivaroxaban and Tranexamic Acid on Blood Conservation in Minimally Invasive Total Knee Arthroplasty a Double-Blind Randomized, Controlled Trial. AB - BACKGROUND: Tranexamic acid (TXA) was reportedly to decrease postoperative blood loss after standard total knee arthroplasty (TKA). However, the blood conservation effect of TXA in minimally invasive TKA, in particular, receiving a direct oral anticoagulant was unclear. The aim of the study was to investigate the efficacy of combined use of TXA and rivaroxaban on postoperative blood loss in primary minimally invasive TKA. METHODS: In a prospective, randomized, controlled trial, 198 patients were assigned to placebo (98 patients, normal saline injection) and study group (100 patients, 1g TXA intraoperative injection) during primary unilateral minimally invasive TKA. All patients received rivaroxaban 10 mg each day for 14 doses postoperatively. Total blood loss was calculated from the maximum hemoglobin drop after surgery plus amount of transfusion. The transfusion rate and wound complications were recorded in all patients. Deep-vein thrombosis was detected by ascending venography of the leg 15 days postoperatively. RESULTS: The mean total blood loss was lower in the study group (1020 mL [95% confidence interval, 960-1080 mL]) compared with placebo (1202 mL [95% confidence interval, 1137-1268 mL]) (P < .001). The transfusion rate was lower in the study group compared with placebo (1% vs 8.2%, P = .018). Postoperative wound hematoma and ecchymosis were higher in placebo than the study group (P = .003). There was no symptomatic deep-vein thrombosis or pulmonary embolism in either group. CONCLUSION: Systemic administration of TXA can effectively reduce the postoperative blood loss which results in lower rate of transfusion requirement and wound hematoma in minimally invasive TKA patients when rivaroxaban is used for thromboprophylaxis. Rivaroxaban has a high rate of bleeding complications when used alone in TKA patients. PMID- 27663189 TI - Parental Cognitive Errors Mediate Parental Psychopathology and Ratings of Child Inattention. AB - We investigate the Depression-Distortion Hypothesis in a sample of 199 school aged children with ADHD-Predominantly Inattentive presentation (ADHD-I) by examining relations and cross-sectional mediational pathways between parental characteristics (i.e., levels of parental depressive and ADHD symptoms) and parental ratings of child problem behavior (inattention, sluggish cognitive tempo, and functional impairment) via parental cognitive errors. Results demonstrated a positive association between parental factors and parental ratings of inattention, as well as a mediational pathway between parental depressive and ADHD symptoms and parental ratings of inattention via parental cognitive errors. Specifically, higher levels of parental depressive and ADHD symptoms predicted higher levels of cognitive errors, which in turn predicted higher parental ratings of inattention. Findings provide evidence for core tenets of the Depression-Distortion Hypothesis, which state that parents with high rates of psychopathology hold negative schemas for their child's behavior and subsequently, report their child's behavior as more severe. PMID- 27663191 TI - Can We Predict Discharge Status After Total Joint Arthroplasty? A Calculator to Predict Home Discharge. AB - BACKGROUND: Postoperative discharge to a skilled nursing facility after total joint arthroplasty (TJA) is associated with increased costs, complications, and readmission. The purpose of this study was to identify the risk factors for discharge to a location other than home to build a calculator to predict discharge disposition after TJA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2011 to 2013 to identify patients who underwent primary total hip or total knee arthroplasty. Risk factors were compared between patients discharging home vs a facility. Predictors of facility discharge were converted to discrete values to develop a simple numerical calculator. RESULTS: After primary TJA, patients discharged to a facility were typically older (70.9 vs 64.3, P < .001), female (69.5% vs 55.7%, P < .001), had an elevated American Society of Anesthesiologist (ASA) class, and were more likely to be functionally dependent before surgery (3.8% vs 1.1%, P < .001). Patient age, preoperative functional status, nonelective THA for hip fracture, and ASA class were most predictive of facility discharge. After development of a predictive model, scores exceeding 40 and 80 points resulted in a facility discharge probability of 75% and 99%, respectively. CONCLUSION: In patients undergoing TJA, advanced age, elevated ASA class, and functionally dependent status before surgery strongly predicted facility discharge. Given that facility discharge imposes a significant cost and morbidity burden after TJA, patients, surgeons, and hospitals may use this simple calculator to target this susceptible patient population. PMID- 27663192 TI - Case conference primary-secondary care planning at end of life can reduce the cost of hospitalisations. AB - BACKGROUND: To plan integrated care at end of life for people with either heart failure or lung disease, we used a case conference between the patient's general practitioner (GP), specialist services and a palliative care consultant physician. This intervention significantly reduced hospitalisations and emergency department visits. This paper reports estimates of potential savings of reduced hospitalisation through end of life case conferences in a pilot study. METHODS: We used Australian Refined Diagnosis Related Group codes to obtain data on hospitalisations and costs. The Australian health system is a federation: the national government is responsible for funding community based care, while state and territory governments fund public hospitals. There were 35 case conferences for patients with end stage heart failure or lung disease, who were patients of the public hospital system, involving 30 GPs in a regional health district. RESULTS: The annualised total cost per patient was AUD$90,060 before CC and AUD$11,841 after CC. The mean per person cost saving was AUD$41,023 ($25,274 excluding one service utilisation outlier). For every 100 patients with end of life heart failure and lung disease each year, the case conferencing intervention would save AUD$4.1 million (AUD$2.5 million excluding one service utilisation outlier). CONCLUSIONS: Multidisciplinary case conferences that promote integrated care among specialists and GPs resulted in substantial cost savings while providing care. Cost shifting between national and state or territory governments may impede implementation of this successful health service intervention. An integrated model such as ours is very relevant to initiatives to reform national health care. TRIAL REGISTRATION: Australian and New Zealand Controlled Trials Register ACTRN12613001377729 : Registered 16/12/2013. PMID- 27663193 TI - Genetic mapping of Pinus flexilis major gene (Cr4) for resistance to white pine blister rust using transcriptome-based SNP genotyping. AB - BACKGROUND: Linkage of DNA markers with phenotypic traits provides essential information to dissect clustered genes with potential phenotypic contributions in a target genome region. Pinus flexilis E. James (limber pine) is a keystone five needle pine species in mountain-top ecosystems of North America. White pine blister rust (WPBR), caused by a non-native fungal pathogen Cronartium ribicola (J.C. Fisch.), has resulted in mortality in this conifer species and is still spreading through the distribution. The objective of this research was to develop P. flexilis transcriptome-wide single nucleotide polymorphism (SNP) markers using RNA-seq analysis for genetic mapping of the major gene (Cr4) that confers complete resistance to C. ribicola. RESULTS: Needle tissues of one resistant and two susceptible seedling families were subjected to RNA-seq analysis. In silico SNP markers were uncovered by mapping the RNA-seq reads back to the de novo assembled transcriptomes. A total of 110,573 in silico SNPs and 2,870 indels were identified with an average of 3.7 SNPs per Kb. These SNPs were distributed in 17,041 unigenes. Of these polymorphic P. flexilis unigenes, 6,584 were highly conserved as compared to the genome sequence of P. taeda L (loblolly pine). High throughput genotyping arrays were designed and were used to search for Cr4-linked genic SNPs in megagametophyte populations of four maternal trees by haploid segregation analysis. A total of 32 SNP markers in 25 genes were localized on the Cr4 linkage group (LG). Syntenic relationships of this Cr4-LG map with the model conifer species P. taeda anchored Cr4 on Pinus consensus LG8, indicating that R genes against C. ribicola have evolved independently in different five-needle pines. Functional genes close to Cr4 were annotated and their potential roles in Cr4-mediated resistance were further discussed. CONCLUSIONS: We demonstrated a very effective, low-cost strategy for developing a SNP genetic map of a phenotypic trait of interest. SNP discovery through transcriptome comparison was integrated with high-throughput genotyping of a small set of in silico SNPs. This strategy may be applied to mapping any trait in non-model plant species that have complex genomes. Whole transcriptome sequencing provides a powerful tool for SNP discovery in conifers and other species with complex genomes, for which sequencing and annotation of complex genomes is still challenging. The genic SNP map for the consensus Cr4-LG may help future molecular breeding efforts by enabling both Cr4 positional characterization and selection of this gene against WPBR. PMID- 27663194 TI - The dorsolateral striatum selectively mediates extinction of habit memory. AB - Previous research has indicated a role for the dorsolateral striatum (DLS) in acquisition and retrieval of habit memory. However, the neurobiological mechanisms guiding extinction of habit memory have not been extensively investigated. The present study examined whether the dorsolateral striatum (DLS) is involved in extinction of habit memory in a food-rewarded response learning version of the plus-maze in adult male Long-Evans rats (experiment 1). In addition, to determine whether the role of this brain region in extinction is selective to habit memory, we also examined whether the DLS is required for extinction of hippocampus-dependent spatial memory in a place learning version of the plus-maze (experiment 2). Following acquisition in either task, rats received two days of extinction training, in which the food reward was removed from the maze. The number of perseverative trials (a trial in which the rat made the same previously reinforced body-turn) and latency to reach the previously correct food well were used as measures of extinction. Animals were given immediate post training intra-DLS administration of the sodium channel blocker bupivacaine or vehicle to determine the effect of DLS inactivation on consolidation of extinction memory in each task. In the response learning task, post-training DLS inactivation impaired consolidation of extinction memory. Injections of bupivacaine delayed 2 h post-training did not affect extinction, indicating a time-dependent effect of neural inactivation on consolidation of extinction memory in this task. In contrast, post-training DLS inactivation did not impair, but instead slightly enhanced, extinction memory in the place learning task. The present findings indicate a critical role for the DLS in extinction of habit memory in the response learning task, and may be relevant to understanding the neural mechanisms through which maladaptive habits in human psychopathologies (e.g. drug addiction) may be suppressed. PMID- 27663195 TI - Workforce planning and development in times of delivery system transformation. AB - BACKGROUND: As implementation of the US Affordable Care Act (ACA) advances, many domestic health systems are considering major changes in how the healthcare workforce is organized. The purpose of this study is to explore the dynamic processes and interactions by which workforce planning and development (WFPD) is evolving in this new environment. METHODS: Informed by the theory of loosely coupled systems (LCS), we use a case study design to examine how workforce changes are being managed in Kaiser Permanente and Montefiore Health System. We conducted site visits with in-depth interviews with 8 to 10 stakeholders in each organization. RESULTS: Both systems demonstrate a concern for the impact of change on their workforce and have made commitments to avoid outsourcing and layoffs. Central workforce planning mechanisms have been replaced with strategies to integrate various stakeholders and units in alignment with strategic growth plans. Features of this new approach include early and continuous engagement of labor in innovation; the development of intermediary sense-making structures to garner resources, facilitate plans, and build consensus; and a whole system perspective, rather than a focus on single professions. We also identify seven principles underlying the WFPD processes in these two cases that can aid in development of a new and more adaptive workforce strategy in healthcare. CONCLUSIONS: Since passage of the ACA, healthcare systems are becoming larger and more complex. Insights from these case studies suggest that while organizational history and structure determined different areas of emphasis, our results indicate that large-scale system transformations in healthcare can be managed in ways that enhance the skills and capacities of the workforce. Our findings merit attention, not just by healthcare administrators and union leaders, but by policymakers and scholars interested in making WFPD policies at a state and national level more responsive. PMID- 27663196 TI - Variation of global DNA methylation levels with age and in autistic children. AB - BACKGROUND: The change in epigenetic signatures, in particular DNA methylation, has been proposed as risk markers for various age-related diseases. However, the course of variation in methylation levels with age, the difference in methylation between genders, and methylation-disease association at the whole genome level is unclear. In the present study, genome-wide methylation levels in DNA extracted from peripheral blood for 2116 healthy Chinese in the 2-97 age range and 280 autistic trios were examined using the fluorescence polarization-based genome wide DNA methylation quantification method developed by us. RESULTS: Genome-wide or global DNA methylation levels proceeded through multiple phases of variation with age, consisting of a steady increase from age 2 to 25 (r = 0.382) and another rise from age 41 to 55 to reach a peak level of ~80 % (r = 0.265), followed by a sharp decrease to ~40 % in the mid-1970s (age 56 to 75; r = -0.395) and leveling off thereafter. Significant gender effect in methylation levels was observed only for the 41-55 age group in which methylation in females was significantly higher than in males (p = 0.010). In addition, global methylation level was significantly higher in autistic children than in age-matched healthy children (p < 0.001). CONCLUSIONS: The multiphasic nature of changes in global methylation levels with age was delineated, and investigation into the factors underlying this profile will be essential to a proper understanding of the aging process. Furthermore, this first report of global hypermethylation in autistic children also illustrates the importance of age-matched controls in characterization of disease-associated variations in DNA methylation. PMID- 27663197 TI - Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study. AB - BACKGROUND: The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases. RESULTS: Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 MUmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 MUmol/L (20.0-2274.0 MUmol/L); it decreased to 40.0 MUmol/L in patients who were alive (13.0-181.0 MUmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to <= 100 MUmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another treatment for hyperammonemia (sodium phenylacetate + sodium benzoate, haemofiltration). Eighteen side effects were reported related to the i.v. infusion (local diffusion, oedema). CONCLUSION: This 10-year retrospective study shows that i.v. sodium benzoate associated with an emergency regimen is an effective and safe treatment for acute episodes of UCD. PMID- 27663198 TI - Multimorbidity, health and aging in Canada and Australia: a tale of two countries. AB - BACKGROUND: Multimorbidity has been recognized as a major public health issue, negatively affecting health-related quality of life, including physical, functional, mental, emotional, and social domains, as well as increasing health care utilization. This exploratory study examines selected health outcomes associated with multimorbidity across older age groups/cohorts and gender, comparing Canada and Australia. METHODS: Data were drawn from the 2008/09 Canadian Community Health Survey and the 2009 Australian HILDA survey. Seven major chronic conditions were identical across the two data sets, and were combined into an additive measure of multimorbidity. OLS and logistic regression models were performed within age group (45-54, 55-64, 65-74, 75+) and gender to estimate associations between multimorbidity and several health-related outcomes, including: loneliness, life satisfaction, perceived health, mobility restriction, and hospital stays, adjusting for marital status, education and foreign born status. RESULTS: Overall, country-level differences were identified for perceptions of loneliness, life satisfaction, and perceived health. Australians tended to experience a greater risk of loneliness and lower self-rated health in the face of multimorbidity than Canadians, especially among older men. Canadians tended to experience lower life satisfaction associated with multimorbidity than Australians. No country-level differences were identified for associations between multimorbidity and hospital stays or mobility limitations. CONCLUSIONS: The associations between multimorbidity and health are similar between the two countries but are variable depending on population, age group/cohort, and gender. The strongest country-level associations are for indicators of health-related quality of life, rather than health care or mobility limitation outcomes. PMID- 27663199 TI - Identifying candidates for targeted gait rehabilitation after stroke: better prediction through biomechanics-informed characterization. AB - BACKGROUND: Walking speed has been used to predict the efficacy of gait training; however, poststroke motor impairments are heterogeneous and different biomechanical strategies may underlie the same walking speed. Identifying which individuals will respond best to a particular gait rehabilitation program using walking speed alone may thus be limited. The objective of this study was to determine if, beyond walking speed, participants' baseline ability to generate propulsive force from their paretic limbs (paretic propulsion) influences the improvements in walking speed resulting from a paretic propulsion-targeting gait intervention. METHODS: Twenty seven participants >6 months poststroke underwent a 12-week locomotor training program designed to target deficits in paretic propulsion through the combination of fast walking with functional electrical stimulation to the paretic ankle musculature (FastFES). The relationship between participants' baseline usual walking speed (UWSbaseline), maximum walking speed (MWSbaseline), and paretic propulsion (propbaseline) versus improvements in usual walking speed (?UWS) and maximum walking speed (?MWS) were evaluated in moderated regression models. RESULTS: UWSbaseline and MWSbaseline were, respectively, poor predictors of DeltaUWS (R 2 = 0.24) and DeltaMWS (R 2 = 0.01). Paretic propulsion * walking speed interactions (UWSbaseline * propbaseline and MWSbaseline * propbaseline) were observed in each regression model (R 2 s = 0.61 and 0.49 for ?UWS and ?MWS, respectively), revealing that slower individuals with higher utilization of the paretic limb for forward propulsion responded best to FastFES training and were the most likely to achieve clinically important differences. CONCLUSIONS: Characterizing participants based on both their walking speed and ability to generate paretic propulsion is a markedly better approach to predicting walking recovery following targeted gait rehabilitation than using walking speed alone. PMID- 27663200 TI - Polymorphisms in miR-135a-2, miR-219-2 and miR-211 as well as their interaction with cooking oil fume exposure on the risk of lung cancer in Chinese nonsmoking females: a case-control study. AB - BACKGROUND: The associations between microRNAs and lung cancer have received increasing attention. This study assess the association between polymorphisms in miR-135a-2, miR-219-2 and miR-211 genes and the risk of lung cancer, as well as the gene-environment interaction between these polymorphisms and cooking oil fume exposure. METHODS: A case-control study featuring 268 cases and 266 controls was conducted. The associations of miR-135a-2 rs10459194, miR-219-2 rs10988341 and miR-211 rs1514035 polymorphisms with the risk of lung cancer were analyzed. The gene-environment interactions were also reported on both additive and multiplicative scales. RESULTS: There were no statistically significant associations between the single-nucleotide polymorphisms (SNPs) and lung cancer or lung adenocarcinoma. The individuals with both a risk genotype of miRNA SNPs and exposure to a risk factor (cooking oil fumes) were at higher risk of lung cancer than those with only one of these two risk factors (odd ratios of 2.208, 1.285 and 1.813 for miR-135a-2 rs10459194; 2.164, 1.209 and 1.806 for miR-219-2 rs10988341; and 2.122, 1.146 and 1.725 for miR-211 rs1514035, respectively). However, the measures of biological interaction indicate that there was no such interaction between the three SNPs and exposure to cooking oil fumes on an additive scale. Logistic regression models also suggested that the gene environment interactions were not statistically significant on a multiplicative scale. CONCLUSIONS: There were no significant associations between the polymorphisms in miRNAs (miR-26a-1 rs7372209, miR-605 rs2043556 and miR-16-1 rs1022960) and the risk of lung cancer in the Chinese nonsmoking female population. The interactions between these polymorphisms in miRNAs and cooking oil fume exposure were also not statistically significant. PMID- 27663201 TI - Is radiographic progression in modern rheumatoid arthritis trials still a robust outcome? Experience from tofacitinib clinical trials. AB - BACKGROUND: The detection of statistically significant reductions in radiographic progression during clinical studies in patients with rheumatoid arthritis (RA) has become increasingly difficult over the past decade due to early-escape study designs and declining rates of progression in control-group patients. We investigated the impact of extremes of radiographic data (outliers) and baseline prognostic factors on detection of treatment effects, to provide guidance on future analysis of joint structural data in RA clinical trials. METHODS: Data were from two, phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib in adult patients with moderate to severe RA: ORAL Scan (NCT00847613) and ORAL Start (NCT01039688). These studies detected significant reductions in radiographic progression with tofacitinib 10 mg twice daily (BID) plus background methotrexate (ORAL Scan), and with tofacitinib 5 or 10 mg BID as monotherapy (ORAL Start). We evaluated mean changes from baseline in van der Heijde modified total Sharp score (mTSS) at month 6 and month 12, using analysis of covariance (ANCOVA). A trimmed analysis was used to deal with extremes of data. The impact of baseline prognostic factors on radiographic progression was evaluated using ANCOVA to analyze the mean change from baseline in mTSS for each factor in turn. RESULTS: The analysis included data from 720 patients from ORAL Scan and 880 patients from ORAL Start. Trimmed analyses were unbiased for the true mean estimate and enabled us to remove the effect of influential extreme observations in the data set. Almost all patients had at least one poor prognostic factor at baseline (e.g., high level of disease activity, or positive for rheumatoid factor). The strongest predictor of treatment effect was the severity of radiographic damage at baseline. CONCLUSIONS: A trimmed analysis can establish whether any significant inhibition of structural damage is being driven by extremes of data, and should be one of the sensitivity analyses of choice for structural data in RA clinical trials. Furthermore, analysis of radiographic data based on baseline prognostic factors may reveal increased treatment effects. Application of these methods to analysis of radiographic data from clinical trials in patients with RA, allows a more complete interpretation of data. TRIAL REGISTRATION: Clinicaltrials.gov NCT00847613 (registered 17 February 2009) and NCT01039688 (registered 23 December 2009). PMID- 27663202 TI - Recurrence of second trimester miscarriage and extreme preterm delivery at 16-27 weeks of gestation with a focus on cervical insufficiency and prophylactic cerclage. AB - INTRODUCTION: The objective of this study was to describe recurrence rates of second trimester miscarriage and extreme preterm delivery by phenotype and use of prophylactic cerclage in a register-based cohort. MATERIAL AND METHODS: We included women with a first second trimester miscarriage or extreme preterm delivery (16+0 to 27+6 gestational weeks) in Denmark in 1997-2012 (n = 9602) by combined use of the Danish Medical Birth Register and the Danish National Patient Register. Eight phenotypes were identified by ICD-10 codes in a hierarchy with the following sequence: major fetal anomaly, multiple gestation, uterine anomaly, placental insufficiency, antepartum bleeding, cervical insufficiency, preterm premature rupture of membranes, and intrauterine fetal death. Recurrence rate after a second trimester miscarriage/spontaneous delivery in the period was calculated based on the register data. In cervical insufficiency outcome was stratified by prophylactic cerclage applied <16 weeks of gestation. RESULTS: Overall recurrence rate was 7.3% (n = 452), a rate that differed by phenotype from <5% (fetal anomaly, multiple gestations, intrauterine fetal death) to 21% (cervical insufficiency). In women with cervical insufficiency the recurrence rate was 28% without cerclage; vaginal cerclage was associated with a significant reduction [adjusted odds ratio (OR) 0.47; 95% CI 0.29-0.76] and abdominal cerclage with an even greater reduction (adjusted OR 0.14; 95% CI 0.03-0.61). CONCLUSIONS: The overall recurrence rate of second trimester miscarriage or extreme preterm delivery was 7%, but it differed significantly by phenotype. The highest rate, 28%, was found in cervical insufficiency, and prophylactic cerclage was associated with a significant reduction in recurrence. PMID- 27663203 TI - Epidemiology and fungal species distribution of superficial mycoses in Northeast Brazil. AB - OBJECTIVE: Dermatomycoses are superficial fungal infections which affect the skin, hair and nails of humans and animals. Male and female patients of all ages are affected by this condition. The main etiological agents of dermatomycoses are the dermatophytes fungi of the genera Trichophyton, Microsporum and Epidermophyton, while the main yeasts belong to the genera Candida, Malassezia and Trichosporon. The variation in the distribution of dermatomycoses worldwide justify the conduction of epidemiological studies in order to contribute for the better understanding of patterns of mycological cutaneous infections. This study was conducted from April 2013 to December 2014. MATERIAL AND METHODS: A total of 205 patients were evaluated, while 235 clinical specimens were obtained. From our positive cases of mycological examination, 73 (64.6%) patients were female, while 40 (35.4%) were male. Scales from the skin and nails were collected and observed at optical microscopy after potassium hydroxide clarification. Cultures were performed on Sabouraud Dextrose Agar added chloramphenicol. Identification was performed by classic methodology. RESULTS: We found that the glabrous skin was the largest source of dermatomycoses (30.11%), followed by toenails (27.4%) and fingernails (17.7%). Regarding onychomycosis, the most affected population was over 50 years old. Trichophyton rubrum was the dermatophyte fungal species more commonly found. Most of the patients with pityriasis versicolor were adults and female. Another important fact observed is that Candida parapsilosis was the most prevalent species. Finally, a high incidence of T. tonsurans in cases of superficial mycoses was observed. CONCLUSION: Our results clearly demonstrate peculiarities in terms of etiological agents of dermatophytoses distribution in a specific region of Brazil. PMID- 27663204 TI - The influence of the control group characteristics for the diagnostic performance of 1,3-beta-D-glucan in invasive aspergillosis. PMID- 27663205 TI - The effect of inhibition of PP1 and TNFalpha signaling on pathogenesis of SARS coronavirus. AB - BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS CoV, as well as inflammatory activity driving pathogenesis through TNFalpha signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. PMID- 27663206 TI - Antiobesity and antihyperglycaemic effects of Adiantum capillus-veneris extracts: in vitro and in vivo evaluations. AB - CONTEXT: Adiantum capillus-veneris L. (Adiantaceae) hypocholesterolemic activity is therapeutically praised. OBJECTIVES: Pharmacological modulation of pancreatic triacylglycerol lipase (PL) and alpha-amylase/alpha-glucosidase by A. capillus veneris are evaluated. MATERIALS AND METHODS: Using positive controls (acarbose, orlistat, guar gum, atorvastatin, glipizide and metformin) as appropriate, crude aqueous extracts (AEs) of A. capillus-veneris aerial parts were tested via a combination of in vitro enzymatic (0.24-100 mg/mL), acute in vivo carbohydrate tolerance tests (125, 250 or 500 mg/kg body weight [b.wt]) and chronic in vivo studies (500 mg/kg b.wt) in high cholesterol diet (HCD) fed Wistar rats. RESULTS: Like acarbose, A. capillus-veneris as well as chlorogenic acid, with respective IC50 values (mg/mL) of 0.8 +/- 0.0 and 0.2 +/- 0.0, were identified as in vitro potent dual inhibitors of alpha-amylase/alpha-glucosidase. Unlike guar gum, A. capillus-veneris had no glucose diffusion hindrance capacity. Equivalent to orlistat, A. capillus-veneris and its phytoconstituents inhibited PL in vitro with an ascending order of PL- IC50 values (MUg/mL): ferulic acid; 0.48 +/- 0.06 < ellagic acid; 13.53 +/- 1.83 < chlorogenic acid; 38.4 +/- 2.8 < A. capillus veneris; 1600 +/- 100. Incomparable to acarbose or metformin and glipizide, A. capillus-veneris (125, 250 and 500 mg/kg b.wt) lacked antihyperglycaemic efficacies in acute starch- or glucose-evoked postprandial hyperglycaemia increments in normoglycaemic overnight fasting rats. Superior to atorvastatin; A. capillus-veneris exerted significant antiobesity (p < 0.001) with marked triacylglycerol-reducing capacities (p < 0.001) in comparison to rats fed with HCD for 10 weeks. DISCUSSION AND CONCLUSION: A. capillus-veneris, modulating pancreatic digestive enzymes, may be advocated as a combinatorial diabesity prevention/phytotherapy agent. PMID- 27663207 TI - Inducing a humoral immune response to pancreatic cancer antigen. AB - BACKGROUND: Patients with pancreatic carcinoma have a grim prognosis. Here, we examine the induction of an in vitro antibody response of human B cells to pancreatic carcinoma antigens. MATERIAL AND METHODS: Cells of five cultured pancreatic ductal adenocarcinoma lines were lysed and their plasma membrane fragments isolated in an aqueous two-phase-system. The plasma membrane fragments were then added to cultures of isolated peripheral blood mononuclear cells from healthy volunteers for 14 days to act as a tumor antigen. Also, we added combinations of IL-2, IL-4, IL-21, anti-CD40 mAb and varying protein concentrations of the plasma membrane fragments to these cultures. We then tested characteristics and binding of resulting IgG and IgM against aforementioned tumor plasma membrane fragments and their respective cells using ELISAs. RESULTS: The combination of IL-2, IL-4 and anti-CD40 mAb elicited IgM production showing significant binding (p<0.05) to plasma membrane fragments. PANC-1 antigen and the combination of IL-4, IL-21 and anti-CD40 mAb was able to produce a significant and specific IgG formation against PANC-1 plasma membrane fragments (p<0.05). Tumor antigen, interleukins and anti-CD40 mAb had a significant impact on the binding capacity of these antibodies (p<0.05). IgG binding pancreatic carcinoma cells was observed when the tumor antigen concentration was increased during stimulation (p<0.05). BxPC3 plasma membrane fragments showed inhibitory effects on IgG binding BxPC3 antigens (p<0.05). CONCLUSIONS: A human anti-tumor antibody formation can be induced in vitro using PANC-1 antigens and B cell stimulating agents. This response has the potential to generate antibodies specific to PANC-1 antigens. PReCIS: The concept presented is novel and a promising approach to eliciting a specific B cell response to tumor antigen. The method may prove useful in understanding and developing anti-tumor immunity. PMID- 27663208 TI - Challenges in evaluating cancer as a clinical outcome in postapproval studies of drug safety. AB - Pharmaceuticals approved in the United States are largely not known human carcinogens. However, cancer signals associated with pharmaceuticals may be hypothesized or arise after product approval. There are many study designs that can be used to evaluate cancer as an outcome in the postapproval setting. Because prospective systematic collection of cancer outcomes from a large number of individuals may be lengthy, expensive, and challenging, leveraging data from large existing databases are an integral approach. Such studies have the capability to evaluate the clinical experience of a large number of individuals, yet there are unique methodological challenges involved in their use to evaluate cancer outcomes. To discuss methodological challenges and potential solutions, the Food and Drug Administration and the National Cancer Institute convened a two day public meeting in 2014. This commentary summarizes the most salient issues discussed at the meeting. PMID- 27663210 TI - [Reply to Letter to the Editor: Aetiological diagnosis in meningitis and encephalitis using molecular biology techniques]. PMID- 27663209 TI - The utility of EMR address histories for assessing neighborhood exposures. AB - PURPOSE: Electronic medical records (EMRs) include residential address histories, which may alleviate exposure misclassification caused by exclusion of patient spatiotemporal location. EMR data are increasingly available but rarely leveraged as a measure of cumulative environmental exposure, in part due to limited understanding of the validity of EMR-derived address histories. METHODS: We compared EMR address histories to self-reported histories among 100 patients of a safety-net health care system completing a telephone survey. We assessed agreement and compared seven neighborhood-level environmental exposures as assessed using both data sources. RESULTS: While 17.1% of respondents did not live at the most recent EMR-derived address during the survey, nearly all (98%) lived there at some point. For respondents with more than one EMR-derived address (N = 64), 87.5% had once lived at the previous EMR address. Of these, 30.4% lived at 1 or more additional residences between the two most recent EMR address. For all measures, neighborhood-level environmental exposures did not differ when using EMR-derived versus self-report addresses. CONCLUSIONS: More recent EMR derived addresses are more accurate, and differences compared to self-reported addresses in neighborhood-level exposures are negligible. EMR-derived address histories are incomplete and likely suffer from collection bias; future research should further assess their validity and reliability. PMID- 27663211 TI - Recurrent cerebral infarcts secondary to marantic endocarditis in a patient with adenocarcinoma of the lung. PMID- 27663212 TI - Comparison of serum levels of IL-18 in peripheral blood of patients with type II diabetes with nephropathy clinical protests and patients with type II diabetes without nephropathy clinical protests. AB - BACKGROUND AND AIM: Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes. MATERIALS AND METHODS: 69 diabetic patient that have documented file in two centers (Ali asghar hospital and dialysis center of Imam ali hospital) had selected. 32 patients with type 2 nephropathic diabetes and 37 age- and sex-matched control subjects with type 2 diabetes that haven't any sign and symptom of nephropathy were enrolled.then take 5 ml blood from peripheral veins. Patients with positive CRP were excluded(2 patients in control group and 1 patient in case group). We assessed measured serum IL-18 levels in all patients. FINDINGS: Serum IL-18 levels were significantly elevated in patients with type 2 diabetes with nephropathy as compared with control subjects (serum IL-18 261.29+/-20.25 vs. 167.20+/-13.48 pg/ml, P<0.001. the all patients in case control have upper level of serum IL-18 vs the control group. DISCUSSION AND CONCLUSIONS: Serum levels of IL-18 in nephropathic patient significantly rise and Serum levels of IL-18 might be a predictor factor of progression of diabetic nephropathy. PMID- 27663213 TI - The Impact of Timing of Introduction of Solids on Infant Body Mass Index. AB - OBJECTIVES: To evaluate the associations between breastfeeding duration, age at solids introduction, and their interaction in relation to infant (age 9-15 months) above normal body mass index (BMI). STUDY DESIGN: Cross-sectional, population-based study with 3153 infants from Melbourne (2007-2011). Above normal BMI (z score > 2, equivalent to >97.7th percentile) defined using the World Health Organization standard. RESULTS: Both longer duration of full and any (full or partial) breastfeeding were associated with lower odds of above normal BMI (eg, aOR, 0.37 [95% CI, 0.22-0.60] for full breastfeeding 4-5 months versus 0-1 months). Compared with introduction of solids at 5-6 months, both early and delayed introduction were associated with increased odds of above normal BMI (aOR for 4 months, 1.75 [95% CI, 1.10-2.80] and for >=7 months, 2.64 [95% CI, 1.26 5.54] versus 6 months). Such associations differ by breastfeeding status at 4 months (interaction P = .08). Early introduction of solids was associated with increased odds of above normal BMI in both infants fully or partially breastfed for >=4 months (aOR, 3.66; 95% CI, 1.41-9.51) and those breastfed for <4 months (aOR, 3.11; 95% CI, 1.39-6.97). Introduction of solids at >=7 months was associated with increased odds of above normal BMI (aOR, 5.79; 95% CI, 1.91 17.49) among infants breastfed for <4 months only. CONCLUSION: Introduction of solids at 5-6 months, compared with either early or delayed introduction, is associated with decreased odds of above normal BMI at 1 year of age, regardless of infants' breastfeeding status at 4 months. These results may have implications for public health guidelines with regard to recommendations about the optimal timing of the introduction of solid foods in infancy. PMID- 27663214 TI - What the Primary Care Provider Needs to Know to Diagnose and Care for Adolescents with Type 1 Diabetes. PMID- 27663216 TI - Reply. PMID- 27663215 TI - Complications of Endoscopic Retrograde Cholangiopancreatography in Pediatric Patients; A Systematic Literature Review and Meta-Analysis. AB - OBJECTIVES: To systematically review risks and summarize reported complication rates associated with the performance of endoscopic retrograde cholangiopancreatography (ERCP) in children during the past 2 decades. STUDY DESIGN: A systematic literature search of MEDLINE, Embase, and Web of Science from January 1995 to January 2016 was conducted for observational studies published in English. Studies reporting ERCP complications in patients <21 years without history of liver transplant or cholecystectomy were included. A summary estimate of the proportion of children who experienced complications following ERCP was derived via a random effects meta-analysis. RESULTS: Thirty-two studies involving 2612 children and 3566 procedures were included. Subjects' ages ranged from 3 days to 21 years. Procedures were performed for biliary (54%), pancreatic (38%), and other (8%) indications; 56% of ERCPs were interventional. The pooled complication rate was 6% (95% CI 4%- 8%). Procedural complications included post ERCP pancreatitis (166, 4.7%), bleeding (22, 0.6%), and infections (27, 0.8%). The pooled estimate of post-ERCP pancreatitis was 3% (95% CI 0.02-0.05), and other complications were 1% (95% CI 0.02-0.05). In the subgroup with neonatal cholestasis, the pooled complication rate was 3% (95% CI 0.01-0.07). Adult and pediatric gastroenterologists and surgeons performed the ERCPs. Available data limited the ability to report differences between pediatric-trained and other endoscopists. CONCLUSIONS: Complications associated with pediatric ERCP range widely in severity and are reported inconsistently. Our review suggests 6% of pediatric ERCPs have complications. Further studies that use systematic and standardized methodologies are needed to determine the frequency and risk factors for ERCP-related complications. PMID- 27663218 TI - American Society for Pain Management Nursing Position Statement: Prescribing and Administering Opioid Doses Based Solely on Pain Intensity. PMID- 27663217 TI - Human Subject Effects on Torsion Pendulum Oscillations: Further Evidence of Mediation by Convection Currents. AB - CONTEXT: When a human subject sits beneath a wire mesh, hemispheric torsion pendulum (TP) a rapid-onset series of oscillations at frequencies both higher and lower than the fundamental frequency of the TP have been consistently observed. OBJECTIVE: This study was designed to replicate and extend prior findings that suggest the human subject effect on TP behavior is due to subject-generated, heat induced convection currents. DESIGN: Effects on pendulum behavior were tested after draping an aluminized "space blanket" over the subject and by replacing the subject with a thermal mattress pad shaped to approximate the human form. SETTING: Experiments were performed in a basic science university research laboratory. MAIN OUTCOME MEASURES: Real-time recordings and Fast Fourier Transform frequency spectra of pendulum oscillatory movement. RESULTS: The space blanket blocked, while the mattress pad mimicked, the human subject induced complex array of pendulum oscillations. CONCLUSIONS: Our findings support and strengthen previous results that suggest the effects of human subjects on behavior of a torsion pendulum are mediated by body-heat-induced air convection rather than an unknown type of biofield. PMID- 27663219 TI - A Note on Veracity. PMID- 27663220 TI - Parapharyngeal space primary tumours. AB - INTRODUCTION AND OBJECTIVES: The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. PATIENTS AND METHOD: This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. RESULTS: 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. CONCLUSIONS: Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used. PMID- 27663221 TI - Ossiculoplasty in chronic otitis media: Surgical results and prognostic factors of surgical success. AB - BACKGROUND AND OBJECTIVES: The goal of ossiculoplasty is to improve hearing. Successful ossiculoplasty depends on several factors. This retrospective study was carried out to analyze hearing results of ossiculoplasty in ears with chronic otitis media (COM) and evaluate clinical outcomes and factors predictive of hearing improvement. SUBJECTS AND METHODS: We reviewed the results of 153 patients with COM (with cholesteatoma (COMC) and without cholesteatoma (COMWC)) who underwent ossiculoplasty between January of 2002 to December of 2011. Several potential prognostic factors were evaluated: cholesteatoma present vs absent; type of surgical procedure, state of the middle ear mucosa, state of the ossicular chain, type of prosthesis. RESULTS: We analyzed 153 ossiculoplasties: 96 patients presented COMWC and 57 patients presented COMC. The ossiculoplasties were performed using autologous ossicles for the most part. All ossiculoplasties were carried out in one-stage surgery. In 38% of cases ossiculoplasty was combined with mastoidectomy; in the remaining 62% of cases, ossiculoplasty was performed without mastoidectomy. Ossiculoplasty was successfully achieved in 113 patients (74%). The presence of the stapes superstructure and normal mucosa were significant predictive factors of surgical success. CONCLUSION: The majority of the ossiculoplasties improved hearing status satisfactorily. Multivariate analysis should be performed to investigate prognostic factors of favorable short term hearing outcomes after ossiculoplasty. Better knowledge of these predictive factors may contribute to the surgeon's judgment and the information given to patients. PMID- 27663222 TI - Diagnostic surprise in a Meniere-like syndrome: Jugular bulb diverticulum. PMID- 27663223 TI - Commentary to "Robotic versus open pediatric ureteral reimplantation: Costs and complications from a nationwide sample journal of pediatric urology". PMID- 27663224 TI - Chemical stability and osteogenic activity of plasma-sprayed boron-modified calcium silicate-based coatings. AB - In recent years, CaSiO3 bio-ceramic coatings have attracted great attention because of their good bioactivity. However, their high degradation rates in physiological environment restrict their practical applications. In this work, boron-modified CaSiO3 ceramic (Ca11Si4B2O22, B-CS) coating was developed on Ti substrates by plasma-spraying technique attempting to obtain enhanced chemical stability and osteogenic activity. The B-CS coating possessed significantly increased chemical stability due to the introduction of boron and consequently the modified crystal structure, while maintaining good bioactivity. Scanning electron microscope and immunofluorescence studies showed that better cellular adhesion and extinctive filopodia-like processes were observed on the B-CS coating. Compared with the pure CaSiO3 (CS) coating, the B-CS coating promoted MC3T3-E1 cells attachment and proliferation. In addition, enhanced collagen I (COL-I) secretion, alkaline phosphatase activity, and extracellular matrix mineralization levels were detected from the B-CS coating. According to RT-PCR results, notable up-regulation expressions of mineralized tissue-related genes, such as runt-related transcription factor 2 (Runx2), bone sialoprotein and osteocalcin, and bone morphogenetic protein 7 (BMP-7) were observed on the B-CS coating compared with the CS coating. The above results suggested that Ca11Si4B2O22 coatings possess excellent osteogenic activity and might be a promising candidate for orthopedic applications. PMID- 27663225 TI - The propensity for tropomyosin twisting in the presence and absence of F-actin. AB - A canonical model of muscle alpha-tropomyosin (Tpm1.1), based on molecular mechanics and electron microscopy of different contractile states, shows that the two-stranded coiled-coiled is pre-bent to present a specific molecular-face to the F-actin filament. This conformation is thought to facilitate both filament assembly and tropomyosin sliding across actin to modulate myosin-binding. However, to bind effectively to actin filaments, the 42 nm-long tropomyosin coiled-coil is not strictly canonical. Here, the mid-region of tropomyosin twists an additional ~20 degrees in order to better match the F-actin helix. In addition, the N- and C-terminal regions of tropomyosin polymerize head-to-tail to form continuous super-helical cables. In this case, 9 to 10 residue-long overlapping domains between adjacent molecules untwist relative to each other to accommodate orthogonal interactions between chains in the junctional four-helix nexus. Extensive molecular dynamics simulations show that the twisting and untwisting motions of tropomyosin vary appreciably along tropomyosin length, and in particular that substantial terminal domain winding and unwinding occurs whether tropomyosin is bound to F-actin or not. The local and regional twisting and untwisting do not appear to proceed in a concerted fashion, resembling more of a "wringing-type" behavior rather than a rotation. PMID- 27663226 TI - Whole-body MRI in patients with Non-bacterial Osteitis: Radiological findings and correlation with clinical data. AB - OBJECTIVES: To correlate clinical findings of Non-bacterial Osteitis (NBO) with whole-body MRI (WB-MRI) findings and determine a radiologic index for NBO (RINBO) which allows standardized reporting of WB-MRI. METHODS AND MATERIALS: In a prospective study, 40 patients with diagnosis of NBO underwent clinical examination and WB-MRI in which STIR- and T1- weighted images were assessed for NBO-typical lesions. Parameters of interest for RINBO were: number of radiologically active lesions (RAL), size of the patients' maximum RAL presence of extramedullary and spinal involvement. Results were tested for statistical agreement of clinical and MR-based lesion detection. RINBO was tested for correlation with clinical activity. RESULTS: 62/95 clinically/radiologically active lesions were found in 30/33 patients. In 45 % of the cohort, more active lesions were detected by WB-MRI than by clinical examination. RINBO was a significant predictor for the presence of clinically active lesions. CONCLUSION: WB-MRI is a powerful diagnostic tool for patients with NBO which can reveal asymptomatic disease activity. With RINBO a standardized evaluation approach is proposed which helps assessing radiologic disease burden and predicts clinical disease activity. KEY POINTS: * Whole body MRI is a powerful diagnostic tool for patients with non-bacterial Osteitis. * Whole body MRI can reveal asymptomatic disease activity. * The radiologic index RINBO offers a standardized evaluation approach. PMID- 27663227 TI - Real-time fusion of coronary CT angiography with x-ray fluoroscopy during chronic total occlusion PCI. AB - OBJECTIVES: The purpose of this study was to demonstrate the feasibility of real time fusion of coronary computed tomography angiography (CTA) centreline and arterial wall calcification with x-ray fluoroscopy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: Patients undergoing CTO PCI were prospectively enrolled. Pre-procedural CT scans were integrated with conventional coronary fluoroscopy using prototype software. We enrolled 24 patients who underwent CTO PCI using the prototype CT fusion software, and 24 consecutive CTO PCI patients without CT guidance served as a control group. RESULTS: Mean age was 66 +/- 11 years, and 43/48 patients were men. Real-time CTA fusion during CTO PCI provided additional information regarding coronary arterial calcification and tortuosity that generated new insights into antegrade wiring, antegrade dissection/reentry, and retrograde wiring during CTO PCI. Overall CTO success rates and procedural outcomes remained similar between the two groups, despite a trend toward higher complexity in the fusion CTA group. CONCLUSIONS: This study demonstrates that real-time automated co-registration of coronary CTA centreline and calcification onto live fluoroscopic images is feasible and provides new insights into CTO PCI, and in particular, antegrade dissection reentry-based CTO PCI. KEY POINTS: * Real-time semi-automated fusion of CTA/fluoroscopy is feasible during CTO PCI. * CTA fusion data can be toggled on/off as desired during CTO PCI * Real-time CT calcium and centreline overlay could benefit antegrade dissection/reentry-based CTO PCI. PMID- 27663228 TI - Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. AB - Application of pharmaceutical nanotechnology (nanomedicines) for plant actives and extracts, is gaining a tremendous growth and interest among the scientists. This emerging herbal revolution has headed towards the development of another approaches for the delivery of poorly soluble herbal bioactives and plant extracts for enhancing their bioavailability and efficacy. In the same context, a majority of pharmaceutical nanotechnologies and targeting strategies including phytosomes, nanoparticles, hydrogels, microspheres, transferosomes and ethosomes, self nano emulsifying drug delivery systems (SNEDDS), self micro emulsifying drug delivery systems (SMEDDS) has been applied for the delivery of bioactives and plant extracts and were identified and explored. These pharmaceutical nanotechnologies have been proven to be the most efficient and reliable delivery systems, as these enhance the solubility, absorption, pharmacokinetics, bioavailability and provide protection from toxicity. Considering these aspects, the present review highlights the present scenario related to the expansion of novel herbal formulations utilizing the nanotechnologies and compilation of their delivery types and mechanism, methodology, loaded drug, drug size, entrapment efficiency of drug, in vivo activity and its application. Moreover, this review article provides an understanding of therapeutic efficacy of the herbal medicines to be loaded into the novel drug delivery system for various biomedical applications. PMID- 27663230 TI - Patterns of crop cover under future climates. AB - We study changes in crop cover under future climate and socio-economic projections. This study is not only organised around the global and regional adaptation or vulnerability to climate change but also includes the influence of projected changes in socio-economic, technological and biophysical drivers, especially regional gross domestic product. The climatic data are obtained from simulations of RCP4.5 and 8.5 by four global circulation models/earth system models from 2000 to 2100. We use Random Forest, an empirical statistical model, to project the future crop cover. Our results show that, at the global scale, increases and decreases in crop cover cancel each other out. Crop cover in the Northern Hemisphere is projected to be impacted more by future climate than the in Southern Hemisphere because of the disparity in the warming rate and precipitation patterns between the two Hemispheres. We found that crop cover in temperate regions is projected to decrease more than in tropical regions. We identified regions of concern and opportunities for climate change adaptation and investment. PMID- 27663229 TI - Co-release of dicloxacillin and thioridazine from catheter material containing an interpenetrating polymer network for inhibiting device-associated Staphylococcus aureus infection. AB - Approximately half of all nosocomial bloodstream infections are caused by bacterial colonization of vascular catheters. Attempts have been made to improve devices using anti-adhesive or antimicrobial coatings; however, it is often difficult to bind coatings stably to catheter materials, and the low amounts of drug in thin-film coatings limit effective long-term release. Interpenetrating polymer networks (IPNs) are polymer hybrid materials with unique drug release properties. While IPNs have been extensively investigated for use in tablet- or capsule-based drug delivery systems, the potential for use of IPNs in drug release medical devices remains largely unexplored. Here, we investigated the use of silicone-hydrogel IPNs as a catheter material to provide slow anti-bacterial drug-release functionality. IPN catheters were produced by the sequential method, using supercritical CO2 as a solvent to polymerize and crosslink poly(2 hydroxyethyl methacrylate) (PHEMA) in silicone elastomer. The design was tested against Staphylococcus aureus colonization after loading with dicloxacillin (DCX) alone or in combination with thioridazine (TDZ), the latter of which is known to synergistically potentiate the antibacterial effect of DCX against both methicillin-sensitive and methicillin-resistant S. aureus. The hydrophilic PHEMA component allowed for drug loading in the catheters by passive diffusion and provided controlled release properties. The drug-loaded IPN material inhibited bacterial growth on agar plates for up to two weeks and in blood cultures for up to five days, and it withstood 24h of seeding with resilient biofilm aggregates. The combined loading of DCX+TDZ enhanced the antibacterial efficiency in static in vitro experiments, although release analyses revealed that this effect was due to an enhanced loading capacity of DCX when co-loaded with TDZ. Lastly, the IPN catheters were tested in a novel porcine model of central venous catheter-related infection, in which drug-loaded IPN catheters were found to significantly decrease the frequency of infection. PMID- 27663231 TI - What is at stake? Status and threats to South China Sea marine fisheries. AB - Governance of South China Sea (SCS) fisheries remains weak despite acknowledgement of their widespread overexploitation for the past few decades. This review incorporates unreported fish catches to provide an improved baseline of the current status and societal contribution of SCS marine fisheries, so that the socio-economic and ecological consequences of continued fisheries unsustainability may be understood. Potential fisheries contribution to food and livelihoods include 11-17 million t in fisheries catch and USD 12-22 * 109 in fisheries landed value annually in the 2000s, and close to 3 million jobs. However, overfishing has resulted in biodiversity and habitat loss, and altered ecosystem trophic structures to a 'fished down' state. The present situation reiterates the urgency for fisheries policies that simultaneously address multiple political, social, economic, and biological dimensions at regional, national, and local scales. Importantly, improved cooperation between SCS nations, particularly in overcoming territorial disputes, is essential for effective regional fisheries governance. PMID- 27663232 TI - Backbone modified TBA analogues endowed with antiproliferative activity. AB - BACKGROUND: The thrombin binding aptamer (TBA) is endowed with antiproliferative properties but its potential development is counteracted by the concomitant anticoagulant activity. METHODS: Five oligonucleotides (ODNs) based on TBA sequence (GGTTGGTGTGGTTGG) and containing l-residues or both l-residues and inversion of polarity sites have been investigated by NMR and CD techniques for their ability to form G-quadruplex structures. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay), and their resistance in fetal bovine serum have been tested. RESULTS: CD and NMR data suggest that the investigated ODNs are able to form right- and left-handed G-quadruplex structures. All ODNs do not retain the anticoagulant activity characteristic of TBA but are endowed with a significant antiproliferative activity against two cancerous cell lines. Their resistance in biological environment after six days is variable, depending on the ODN. CONCLUSIONS: A comparison between results and literature data suggests that the antiproliferative activity of the TBA analogues investigated could depends on two factors: a) biological pathways and targets different from those already identified or proposed for other antiproliferative G quadruplex aptamers, and b) the contribution of the guanine-based degradation products. GENERAL SIGNIFICANCE: Modified TBA analogues containing l-residues and inversion of polarity sites lose the anticoagulant activity but gain antiproliferative properties against two cancer cell lines. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. PMID- 27663234 TI - Potential role of Apoptosis Inducing Factor in evolutionarily significant eukaryote, Dictyostelium discoideum survival. AB - Apoptosis Inducing Factor (AIF), a phylogenetically conserved mitochondrial inter membrane space flavoprotein has an important role in caspase independent cell death. Nevertheless, AIF is also essential for cell survival. It is required for mitochondrial organization and energy metabolism. Upon apoptotic stimulation, AIF induces DNA fragmentation after its mitochondrio-nuclear translocation. Although it executes critical cellular functions in a coordinated manner, the exact mechanism still remains obscure. The present study aims to understand AIF's role in cell survival, growth and development by its down-regulation in an interesting unicellular eukaryote, D. discoideum which exhibits multicellularity upon starvation. Constitutive AIF down-regulated (dR) cells exhibited slower growth and delayed developmental morphogenesis. Also, constitutive AIF dR cells manifested high intracellular ROS, oxidative DNA damage and calcium levels with lower ATP content. Interestingly, constitutive AIF dR cells showed amelioration in cell growth upon antioxidant treatment, strengthening its role as ROS regulator. Under oxidative stress, AIF dR cells showed early mitochondrial membrane depolarization followed by AIF translocation from mitochondria to nucleus and exhibited necrotic cell death as compared to paraptoptic cell death of control cells. Thus, the results of this study provide an exemplar where AIF is involved in growth and development by regulating ROS levels and maintaining mitochondrial function in D. discoideum, an evolutionarily significant model organism exhibiting caspase independent apoptosis. PMID- 27663233 TI - Macrophages mediated diagnosis of rheumatoid arthritis using fibrin based magnetic nanoparticles as MRI contrast agents. AB - BACKGROUND: A variety of bioimaging tools assists in the diagnosis and evaluation of rheumatoid arthritis (RA) and other osteoarthritis. However, detection of RA in the early stages by targeting its macrophages with suitable contrast agents will help in arresting the progression of the disease. METHODS: In the present study, we investigated the effectiveness of using magnetic fibrin nanoparticles (MFNPs) conjugated with folic acid (FA-MFNPs) as a specific contrast agent to target the activated macrophages, which overexpress the folate receptors (FR) in the knee joints of rats with antigen-induced arthritis (AIA). RESULTS: FA-MFNPs were spherical with an average size of 18.3+/-1.6nm. In vitro studies have shown effective internalization of FA-MFNPs into the Raw264.7 macrophage cells. In vivo studies were carried out by injecting FA-MFNPs intravenously into the arthritic rats. The results showed enhanced MR imaging in the synovium of arthritic joints. Prussian blue histological staining confirmed uptake of FA-MFNPs by macrophages in the synovial tissue. CONCLUSION: The animal experiment results indicate that FA-MFNPs can be used as a specific MRI contrast agent in identifying phagocytic active macrophages in the synovial joints. GENERAL SIGNIFICANCE: Blood is the precursor source for synthesising the fibrin-based iron oxide (magnetic) nanoparticles (MFNPs) with diameters between 12 and 15nm. It has excellent superparamagnetic behaviour, biocompatibility, osteogenic potency, hemocompatibility, and biodegradable properties. MFNPs-based nanocomposites might be a promising contrast agent for bioimaging. PMID- 27663235 TI - Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer's disease: the National Finnish population study (FINRISK). AB - Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer's disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The follow-up time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely associated with incident AD risk when adjusted for competing risks of death, but the finding is unlikely to be of clinical relevance. Our study does not support the use of these risk markers to predict incident dementia or AD. PMID- 27663236 TI - The Effect of Lateralization of Motor Onset and Emotional Recognition in PD Patients Using EEG. AB - The objective of this research was to investigate the relationship between emotion recognition and lateralization of motor onset in Parkinson's disease (PD) patients using electroencephalogram (EEG) signals. The subject pool consisted of twenty PD patients [ten with predominantly left-sided (LPD) and ten with predominantly right-sided (RPD) motor symptoms] and 20 healthy controls (HC) that were matched for age and gender. Multimodal stimuli were used to evoke simple emotions, such as happiness, sadness, fear, anger, surprise, and disgust. Artifact-free emotion EEG signals were processed using the auto regressive spectral method and then subjected to repeated ANOVA measures. No group differences were observed across behavioral measures; however, a significant reduction in EEG spectral power was observed at alpha, beta and gamma frequency oscillations in LPD, compared to RPD and HC participants, suggesting that LPD patients (inferred right-hemisphere pathology) are impaired compared to RPD patients in emotional processing. We also found that PD-related emotional processing deficits may be selective to the perception of negative emotions. Previous findings have suggested a hemispheric effect on emotion processing that could be related to emotional response impairment in a subgroup of PD patients. This study may help in clinical practice to uncover potential neurophysiologic abnormalities of emotional changes with respect to PD patient's motor onset. PMID- 27663239 TI - Retreatment of polypoidal choroidal vasculopathy after photodynamic therapy combined with intravitreal ranibizumab. AB - PURPOSE: To investigate the incidence, risk factors and effect on visual improvement of retreatment within 60 months after initial photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) in eyes with treatment-naive polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 61 eyes from 60 patients with PCV, who were followed up for at least 12 months after undergoing combination therapy. Retreatment, including combination therapy or IVR alone, was administered if residual or recurrent exudative changes were present. RESULTS: During the follow-up period (mean 44 +/- 13 months, median 48 months), 46 eyes (75.4 %) underwent retreatment. Survival analysis revealed that the proportions of eyes that were retreatment-free were 59 % at the 12-month visit, 41 % at the 24 month, 31 % at the 36 month, and 20 % at the 60-month visit. The median retreatment-free period was 15.0 [95 % confidence interval (CI) 7.4-22.7] months, and the mean period was 24.9 (95 % CI 19.3-30.6) months. Cox regression analysis revealed that older age (P = 0.010, hazard ratio 1.06, CI 1.02-1.11) and male gender (P = 0.043, hazard ratio 2.41, CI 1.03-5.62) were associated with retreatment. Visual improvement was significantly better in eyes without retreatment compared with those with retreatment at the 12-, 24- and 48-month visits. CONCLUSIONS: About 80 % of eyes with PCV require retreatment within 5 years after combination therapy with PDT and IVR. Retreatment is associated with older age and male gender and is related to reduced improvement of visual acuity. PMID- 27663237 TI - Lipidomics: Techniques, Applications, and Outcomes Related to Biomedical Sciences. AB - Lipidomics is a newly emerged discipline that studies cellular lipids on a large scale based on analytical chemistry principles and technological tools, particularly mass spectrometry. Recently, techniques have greatly advanced and novel applications of lipidomics in the biomedical sciences have emerged. This review provides a timely update on these aspects. After briefly introducing the lipidomics discipline, we compare mass spectrometry-based techniques for analysis of lipids and summarize very recent applications of lipidomics in health and disease. Finally, we discuss the status of the field, future directions, and advantages and limitations of the field. PMID- 27663238 TI - 123I-mIBG scintigraphy in neuroblastoma: development of a SIOPEN semi quantitative reporting ,method by an international panel. AB - PURPOSE: A robust method is required to standardise objective reporting of diagnostic 123I-mIBG images in neuroblastoma. Prerequisites for an appropriate system are low inter- and intra-observer error and reproducibility across a broad disease spectrum. We present a new reporting method, developed and tested for SIOPEN by an international expert panel. METHOD: Patterns of abnormal skeletal 123I-mIBG uptake were defined and assigned numerical scores [0-6] based on disease extent within 12 body segments. Uptake intensity was excluded from the analysis. Data sets from 82 patients were scored independently by six experienced specialists as unblinded pairs (pre- and post-induction chemotherapy) and in random order as a blinded study. Response was defined as >=50 % reduction in post induction score compared with baseline. RESULTS: In total, 1968 image sets were reviewed individually. Response rates of 88 % and 82 % were recorded for patients with baseline skeletal scores <=23 and 24-48 respectively, compared with 44 % response in patients with skeletal scores >48 (p = 0.02). Reducing the number of segments or extension scale had a small but statistically negative impact upon the number of responses detected. Intraclass correlation coefficients [ICCs] calculated for the unblinded and blinded study were 0.95 at diagnosis and 0.98 and 0.99 post-induction chemotherapy, respectively. CONCLUSIONS: The SIOPEN mIBG score method is reproducible across the full spectrum of disease in high risk neuroblastoma. Numerical assessment of skeletal disease extent avoids subjective evaluation of uptake intensity. This robust approach provides a reliable means with which to examine the role of 123I mIBG scintigraphy as a prognostic indicator in neuroblastoma. PMID- 27663240 TI - Incidence and patterns of maxillofacial trauma-a retrospective analysis of 3611 patients-an update. AB - BACKGROUND: Maxillofacial fractures occur in a significant proportion worldwide and can occur as an isolated injury or in combination with other severe injuries including cranial, spinal, and upper and lower body injuries requiring prompt diagnosis with possible emergency interventions. The epidemiology of facial fractures varies with regard to injury type, severity, and cause and depends on the population studied. Hence, understanding of these factors can aid in establishing clinical and research priorities for effective treatment and prevention of these injuries. MATERIALS AND METHODS: In this present retrospective study, we provide a comprehensive overview regarding cranio maxillofacial trauma on 3611 patients to assist the clinician in assessment and management of this unique highly specialized area of traumatology. A preformed pro forma was used to analyze the medical records of patients treated for facial trauma in The Department of Oral and Maxillofacial Surgery, Meenakshi Ammal Dental College and Hospital, Chennai. The distribution according to age, gender, etiology, type of injury, time interval between accident and treatment, loss of consciousness, facial bones involved, pattern of fracture lines, treatment offered, and postoperative complications were recorded and evaluated. RESULTS: We inferred male patients sustained more injuries mostly in the third decade of age. Road traffic accidents were the most common cause of injury. Mandible was the most commonly fractured bone in the facial skeleton. Soft tissue injuries occurred more in road traffic accidents and upper lip was the commonest site of injury. CONCLUSION: Our study provides insights into the epidemiology of facial injuries and associated factors and can be useful not only in developing prevention strategies but also for grading the existing legal regulations and also for framing a more effective treatment protocol. PMID- 27663241 TI - Finite element analysis of stress distribution on the mandible and condylar fracture osteosynthesis during various clenching tasks. AB - PURPOSE: The purpose of the study was to evaluate the effect of clenching tasks on the stress and strain of condylar osteosynthesis screws and plates, as well as on the stress, strain distribution and displacement on the whole mandible and bone surrounding screws. METHODS: Three-dimensional finite element models of the mandible, two straight four-hole plates and eight screws were established. Six static clenching tasks were simulated in this study: incisal clench (INC), intercuspal position (ICP), right unilateral molar clench (RMOL), left unilateral molar clench (LMOL), right group function (RGF) and left group function (LGF). RESULTS: Based on the simulation of the six clenching tasks, none of the inserted screws and plates were broken or bended. For the whole mandibular bone, the maximum von Mises stress and von Mises strain observed were yielded by the ICP. For the bone surrounding the inserted screws, the maximum von Mises stress and von Mises strain were yielded by the LMOL (49.2 MPa and 3795.1 MU). CONCLUSION: Clenching tasks had significant effects on the stress distribution on the condylar osteosynthesis and the bone surrounding screws. Contralateral occlusion task (LMOL) had the maximal results of von Mises stress and strain and healing problems could be occur, this result confirms the importance of soft diet after surgery. PMID- 27663242 TI - Surgical defect coverage in oral submucous fibrosis patients with single-stage extended nasolabial flap. AB - PURPOSE: Long standing oral submucous fibrosis (OSMF) is associated with involvement of the oral submucosa and the muscles of mastication leading to difficulty in mouth opening. Various surgical modalities are mentioned for release but each has its own limitations. The aim of the study was to evaluate the postoperative mouth opening in patients of OSMF after excision of fibrous bands followed by coronoidotomy and surgical defect coverage by extended nasolabial flap. METHODS: We evaluated the use of extended nasolabial flaps and coronoidectomy in the management of 11 randomly selected patients with histologically confirmed oral submucous fibrosis. They all had interincisal opening of less than 25 mm and were treated by bilateral release of fibrous bands, coronoidectomy or coronoidotomy, and extended grafting with a nasolabial flap. RESULT: Their interincisal opening improved significantly from a mean of 8.68+/-7 mm to a mean of 36.75+/-4.05 mm at 6-month follow-up. CONCLUSION: The procedure was effective in the management of patients with oral submucous fibrosis, the main disadvantage being the extraoral scars. PMID- 27663245 TI - Calcipotriol/Betamethasone Dipropionate Foam: A Review in Plaque Psoriasis. AB - Calcipotriol/betamethasone dipropionate foam (Enstilar(r)) is a once-daily synthetic vitamin D3 analogue and synthetic corticosteroid fixed-dose combination foam formulation that is indicated for the topical treatment of plaque psoriasis in adults. In randomized, multicentre trials, treatment with calcipotriol/betamethasone dipropionate foam for 4 weeks resulted in greater proportions of patients achieving treatment success [of the body (i.e. trunk and/or limbs), as assessed by a physician] compared with 4 weeks' treatment with the foam vehicle, individual components as foam, or calcipotriol/betamethasone dipropionate fixed-dose combination as an ointment, or 8 weeks' treatment with the fixed-dose combination as a topical suspension. Treatment with calcipotriol/betamethasone dipropionate foam resulted in significantly lower modified psoriasis area and severity index scores and, where assessed, greater improvements from baseline to week 4 in itch-related sleep loss and health related quality of life than its comparators; results were mixed for patient assessed improvements in itch. Overall, adverse events were mostly mild or moderate in severity, and the most commonly reported treatment-related adverse events were application-site events. Notably, there were no reports of clinically relevant effects on calcium homeostasis or the hypothalamic-pituitary-adrenal axis. Calcipotriol/betamethasone dipropionate foam is a useful new option for patients with plaque psoriasis. PMID- 27663244 TI - Ultrastructural characterization of Pleistophora macrozoarcidis Nigerelli 1946 (Microsporidia) infecting the ocean pout Macrozoarces americanus (Perciformes, Zoarcidae) from the gulf of Maine, MA, USA. AB - Pleistophora macrozoarcidis a microsporidian parasite infecting the muscle tissue of the ocean pout Macrozoarces americanus collected from the Gulf of Maine of the Atlantic Ocean, MA, USA, was morphologically described on the basis of ultrastructural features. Infection was detected as opaque white or rusty brown lesions scattered throughout the musculature of the fish mainly in the region anterior to anus. Transmission electron microscopy showed that in individual parasitized muscle cells, the infection progresses within parasite formed vesicles which are in direct contact with muscle cell elements. The earliest observed parasitic stages are the globular multinucleated proliferative cells or plasmodia limited by a highly tortuous plasmalemma with intervesicular finger like digitations projecting into the parasite cytoplasm. These cells divided through the invagination of the plasmalemma and the amorphous coat producing daughter-cells. Fine electron-dense secretion is deposited on the plasmalemma that causes its thickening which is a sign of commencement of the sporogonic phase. This phase is carried out by cytokinesis of the sporonts and results in the formation of sporoblasts and finally spores. Mature spore has a thin electron dense exospore, a thick electron-lucent endospore, and the plasma membrane which encloses the spore contents. A single nucleus is centrally located with the posterior region containing a posterior vacuole. The majority of spores have 7-13 coils in 1-2 rows, and a small group of spores had about 23 coils forming two rows. Events of polar filament extrusion for penetration of uninfected cells were studied. The polaroplast membranes were expanded and occupy most of the length of the spore. The coils are dislocated from the sides of the spore to throughout the entire sporoplasm. The polar filament everts and extrudes through the polar cap with a sufficient force to pierce adjacent sporophorous vesicle walls. After eversion, the polar filament is referred to as a polar tubule, as it forms a tube through which the sporoplasm travels. It pierces anything in its path and deposits the sporoplasm at a new location to begin another infective cycle. PMID- 27663246 TI - Mining Health Social Media with Sentiment Analysis. AB - With the rapid development of the Internet, more and more users utilize health communities (known as forums) to find health-related information, share their medical stories and experiences, or interact with other people in the communities. In this paper, we propose a framework to analyze the user-generated contents in a health community. The proposed framework contains three phases. First, we extract medical terms, including conditions, symptoms, treatments, effectiveness and side effects to form a virtual document for each question in the community. Next, we modify Latent Dirichlet Allocation (LDA) by adding a weighted scheme, called conLDA, to cluster virtual documents with similar medical term distributions into a conditional topic (C-topic). Finally, we analyze the clustered C-topics by sentiment polarities, and physiological and psychological sentiment. The experiment results show that conLDA outperforms the original LDA, and can cluster relevant medical terms and relevant questions together. The C topics clustered by conLDA are more thematic than those clustered by the original LDA. The results of sentiment analysis may provide a quick reference and valuable insights for patients, caregivers and doctors. PMID- 27663249 TI - The value of transient ischemic dilation for detecting restenosis after coronary artery revascularization. AB - AIM: Transient ischemic dilation (TID) is a marker of severe coronary artery disease (CAD). We aimed to assess the incremental value of TID in a cohort of patients with known significant CAD who had recurrence of symptoms after revascularization. METHODS: We identified in our databases 104 patients who had recent coronary revascularization and recurrence of symptoms. 62 patients had PCI (75 arteries) and 42 patients had CABG (104 arteries). All had follow-up stress SPECT MPI and repeat coronary angiography. Myocardial perfusion findings of ischemia and TID were correlated with presence of significant obstructive CAD (>70% stenosis). RESULTS: Follow-up stress Tc-99m Sestamibi SPECT MPI revealed inducible ischemia in 38 patients (36.5%) and TID > 1.20 in 49 patients (47%). Subsequent coronary angiography showed significant obstructive CAD in 44 patients (42%). The sensitivity for detecting obstructive CAD was 61% for SPECT MPI alone, but increased significantly to 93% by the addition of TID as a diagnostic criterion (P < 0.0001). CONCLUSIONS: In this selected patient cohort with prior coronary revascularization, TID is an important marker of obstructive CAD and has incremental value over SPECT MPI alone. PMID- 27663247 TI - Comparison of clinicopathological features and prognosis of gastric cancer located in the lesser and greater curve. AB - PURPOSE: Little is known about the features of gastric cancer located in the lesser and greater curve. This study aims to investigate the clinicopathological features and prognosis of gastric cancer located in the lesser and greater curve. PATIENTS: From September 2008 to March 2015, 780 gastric cancer patients were enrolled in the present study. The associations between locations and features of patients were analyzed. RESULTS: There were 571 male (73.2 %) and 209 female (26.8 %) patients. The median age was 56 years (ranged 21-86). There were 684 tumors located in the lesser curve (87.7 %) and 96 located in the greater curve (12.3 %). The incidence of melena was significantly lower in patients with tumors located in the lesser curve than that in the greater curve (8.5 vs 15.6 %, P = 0.024). The median size of tumors in the lesser curve was significantly larger than that in the greater curve (5.0 (0.3-15) vs 4.0 cm (0.5-15), P = 0.001). The remaining clinicopathological features were comparable between the two groups (all P > 0.05). Tumor location was not a risk factor for the prognosis of gastric cancer by univariate and multivariate analysis (both P > 0.05). The postoperative complications (all P > 0.05) and prognoses (P = 0.279) were comparable between tumors located in the lesser and greater curve. CONCLUSIONS: The ratio of gastric cancer located in the lesser to greater curve was 7.1:1. Compared with tumors located in the greater curve, the incidence of melena was significantly lower and the tumor size was significantly larger in tumors located in the lesser curve. The prognoses were comparable between tumors located in the lesser and greater curve. PMID- 27663243 TI - Epigenetic impacts of endocrine disruptors in the brain. AB - The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex specific manner. PMID- 27663250 TI - Cardiovascular disease in the literature: A selection of recent original research papers. PMID- 27663252 TI - Cardiac PET/MRI enters the clinical arena! Finally.... PMID- 27663251 TI - Prognostic impact of SPECT-MPI after renal transplantation. AB - BACKGROUND: While renal transplantation is increasingly performed for end-stage renal disease, there is a paucity of data on cardiac screening and prognostication post-transplant. We determined the prognostic value of SPECT-MPI in a cohort who underwent renal transplantation. METHODS: Among 4933 renal transplant recipients identified from the Canadian Organ Replacement Register, we examined outcomes of patients who underwent SPECT-MPI in Ontario, Canada. We determined morbidity and mortality using hospitalization and vital statistics registries, according to SPECT-MPI findings. RESULTS: We studied 282 renal transplant recipients (median age 46 years [25th, 75th percentile 37, 58]) with detailed SPECT-MPI results available, followed for a median of 5.7 (3.3, 7.7) years. Among those undergoing SPECT-MPI (66% pharmacologic stress), 41% had an abnormal summed stress score (SSS > 0) and 31% demonstrated abnormal summed difference score (SDS > 0). Rates of cardiovascular death were 0.4 per 100 person years among those with normal stress perfusion (SSS = 0) and 0.4 per 100 person years with SDS = 0. After adjusting for age, sex, prior myocardial infarction (MI), and cardiac risk factors, an SSS >= 4 conferred increased risk of cardiovascular death or cardiovascular hospitalization with adjusted hazard ratios of 2.52 (95% CI 1.41, 4.52, P = .002) for SSS 4-6 and 2.61 (95% CI 1.52, 4.49, P < .001) for SSS >= 7. SDS was a significant predictor of cardiovascular death or hospitalization, with adjusted hazard ratios of 2.96 (95% CI 1.72, 5.09, P < .001) for SDS 4-6 and 3.26 (95% CI 1.64, 6.50, P < .001) for SDS >= 7. CONCLUSION: Among renal transplant recipients, SPECT-MPI predicted risk of cardiovascular death and cardiovascular hospitalization events. PMID- 27663253 TI - Continuous Gradient Temperature Raman Spectroscopy of Oleic and Linoleic Acids from -100 to 50 degrees C. AB - We analyzed the unsaturated fatty acids oleic (OA, 18:1n-9) and linoleic (LA, 18:2n-3), and a 3:1 LA:OA mixture from -100 to 50 degrees C with continuous gradient temperature Raman spectroscopy (GTRS). The 20 Mb three-dimensional data arrays with 0.2 degrees C increments and first/second derivatives allowed rapid, complete assignment of solid, liquid, and transition state vibrational modes. For OA, large spectral and line width changes occurred in the solid state gamma to alpha transition near -4 degrees C, and the melt (13 degrees C) over a range of only 1 degrees C. For LA, major intensity reductions from 200 to 1750 cm-1 and some peak shifts marked one solid state phase transition at -50 degrees C. A second solid state transition (-33 degrees C) had minor spectral changes. Large spectral and line width changes occurred at the melt transition (-7 degrees C) over a narrow temperature range. For both molecules, melting initiates at the diene structure, then progresses towards the ends. In the 3:1 LA:OA mixture, some less intense and lower frequencies present in the individual lipids are weaker or absent. For example, modes assignable to C8 rocking, C9H-C10H wagging, C10H-C11H wagging, and CH3 rocking are present in OA but absent in LA:OA. Our data quantify the concept of lipid premelting and identify the flexible structures within OA and LA, which have characteristic vibrational modes beginning at cryogenic temperatures. PMID- 27663255 TI - Editorial Introduction to the Special Issue on Neuropsychological Interventions. PMID- 27663254 TI - Phytosterol Esterification is Markedly Decreased in Preterm Infants Receiving Routine Parenteral Nutrition. AB - Several studies reported the association between total plasma phytosterol concentrations and the parenteral nutrition-associated cholestasis (PNAC). To date, no data are available on phytosterol esterification in animals and in humans during parenteral nutrition (PN). We measured free and esterified sterols (cholesterol, campesterol, stigmasterol, and sitosterol) plasma concentrations during PN in 16 preterm infants (500-1249 g of birth weight; Preterm-PN), in 11 term infants (Term-PN) and in 12 adults (Adult-PN). Gas chromatography-mass spectrometry was used for measurements. Plasma concentrations of free cholesterol (Free-CHO), free phytosterols (Free-PHY) and esterified phytosterols (Ester-PHY) were not different among the three PN groups. Esterified cholesterol (Ester-CHO) was statistically lower in Preterm-PN than Adult-PN. Preterm-PN had significantly higher Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios than Adult-PN (Free CHO/Ester-CHO: 1.1 +/- 0.7 vs. 0.6 +/- 0.2; Free-PHY/Ester-PHY: 4.1 +/- 2.6 vs. 1.3 +/- 0.8; *P < 0.05). Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios of Term PN (Free-CHO/Ester-CHO: 1.1 +/- 0.4; Free-PHY/Ester-PHY: 2.9 +/- 1.7) were not different from either Preterm-PN or from Adult-PN. Plasma Free-CHO/Ester-CHO and Free-PHY/Ester-PHY were unchanged after 24 h on fat-free PN both in Preterm-PN and in Adult-PN. Free-PHY/Ester-PHY did not correlate with phytosterol intake in Preterm-PN. Free-PHY/Ester-PHY of Preterm-PN was positively correlated with the Free-CHO/Ester-CHO and negatively correlated with gestational age and birth weight. In conclusion, PHY were esterified to a lesser extent than CHO in all study groups; the esterification was markedly decreased in Preterm-PN compared to Adult-PN. The clinical consequences of these findings warrant further investigations. PMID- 27663256 TI - The Special Supplemental Nutrition Program for Women, Infants, and Children Fresh Start Randomized Controlled Trial: Baseline Participant Characteristics and Reliability of Measures. AB - BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Fresh Start (WFS) is a randomized controlled trial of nutrition education to promote farmers' market fruit and vegetable (F/V) purchases and consumption among women enrolled in WIC. OBJECTIVES: To describe the baseline characteristics (demographics and F/V intake [including F/V juice]) of WFS participants, compare the characteristics with those of WIC participants in New Jersey and nationwide, and examine the baseline reliability of study measures. DESIGN: Cross-sectional. PARTICIPANTS/SETTING: Seven hundred forty-four women served by a New Jersey-based WIC agency located in a densely populated, urban area. MAIN OUTCOME MEASURES: Demographic characteristics; newly developed measures of farmers' market-related knowledge, attitudes, and skills; and validated measures of F/V intake. STATISTICAL ANALYSES: Descriptive statistics to characterize the sample. One-sample t and one-sample sign tests to compare the characteristics with reference values. For dietary behaviors, comparisons were with state and national estimates of the frequency and quantity of F/V intake. RESULTS: Participants had a mean age of 28.9+/-6.8 years and were predominantly Hispanic (59%), US-born (60%), never married (41%), unemployed (62%), receiving assistance other than WIC (70%), and food insecure (55%). Half reported a high school education or less. Higher proportions of WFS participants than WIC participants nationwide were represented among demographic groups at increased risk of inadequate F/V intake. WFS participants consumed more fruit (2.7 cups/day) but less vegetables (1.4 cups/day) than did women nationwide (1.1 and 1.4 cups/day, respectively; P<0.01). Although participants consumed recommended amounts of fruit, their vegetable intake was below recommended levels. All but two of the measures developed for the study had reliability coefficients at or above 0.60. CONCLUSIONS: Intervention is warranted to improve participants' vegetable intake. Registered dietitian nutritionists should be aware of F/V intake differences that may require differential intervention strategies. PMID- 27663258 TI - Scoping review of medical assessment units and older people with complex health needs. AB - OBJECTIVES: To explore current knowledge of medical assessment units (MAUs) with specific reference to older people with complex needs and to stimulate new topics and questions for future policy, research and practice. METHODS: A scoping review was conducted using an integrated-latent thematic approach. RESULTS: This review provides a unique perspective on MAUs and older people which is framed using four themes: efficiency, effectiveness, equity and time. Eighteen articles were reviewed. Most (14) articles reported on efficiency and effectiveness while none reported explicitly on equity. Time was identified as a fourth, latent theme within the literature. CONCLUSION: Findings from this review indicate that future policy, research and practice relating to MAUs should focus on older people with complex needs, patient-centred metrics and those MAU characteristics most likely to deliver positive health outcomes to this particular cohort of patients. PMID- 27663257 TI - Advances in Imaging and Automated Quantification of Pulmonary Diseases in Non neoplastic Diseases. AB - Histological examination has always been the gold standard for the detection and quantification of lung remodeling. However, this method has some limitations regarding the invasiveness of tissue acquisition. Quantitative imaging methods enable the acquisition of valuable information on lung structure and function without the removal of tissue from the body; thus, they are useful for disease identification and follow-up. This article reviews the various quantitative imaging modalities used currently for the non-invasive study of chronic obstructive pulmonary disease, asthma, and interstitial lung diseases. Some promising computer-aided diagnosis methods are also described. PMID- 27663259 TI - Increasing spinal 5-HT2A receptor responsiveness mediates anti-allodynic effect and potentiates fluoxetine efficacy in neuropathic rats. Evidence for GABA release. AB - Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT2A) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia. Tactile allodynia was assessed in spinal nerve ligation induced neuropathic pain in rats using von Frey filaments after acute treatment with TAT-2ASCV and/or 5-HT2A receptor agonist, alone or in combination with repeated treatment with fluoxetine. In vivo microdialysis was performed in order to examine the involvement of GABA in TAT-2ASCV/fluoxetine treatment-associated analgesia. TAT-2ASCV (100ng, single i.t. injection) improved SNL-induced tactile allodynia by increasing 5-HT2A receptor responsiveness to endogenous 5-HT. Fluoxetine alone (10mg/kg, five i.p. injections) slightly increased tactile thresholds and its co-administration with TAT-2ASCV (100ng, single i.t. injection) further enhanced the anti-allodynic effect. This effect depends on the integrity of descending serotonergic bulbospinal pathways and spinal release of GABA. The anti-allodynic effect of fluoxetine can be enhanced by disrupting 5 HT2A receptor-PDZ protein interactions. This enhancement depends on 5-HT2A receptor activation, spinal GABA release and GABAA receptor activation. PMID- 27663260 TI - To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling. AB - Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P1). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P1 modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling. PMID- 27663261 TI - Nitrosopersulfide (SSNO-) targets the Keap-1/Nrf2 redox system. AB - Nitric oxide (NO), hydrogen sulfide and polysulfides have been proposed to contribute to redox signaling by activating the Keap-1/Nrf2 stress response system. Nitrosopersulfide (SSNO-) recently emerged as a bioactive product of the chemical interaction of NO or nitrosothiols with sulfide; upon decomposition it generates polysulfides and free NO, triggering the activation of soluble guanylate cyclase, inducing blood vessel relaxation in vitro and lowering blood pressure in vivo. Whether SSNO- itself interacts with the Keap-1/Nrf2 system is unknown. We therefore sought to investigate the ability of SSNO- to activate Nrf2 dependent processes in human vascular endothelial cells, and to compare the pharmacological effects of SSNO- with those of its precursors NO and sulfide at multiple levels of target engagement. We here demonstrate that SSNO- strongly increases nuclear levels, binding activity and transactivation activity of Nrf2, thereby increasing mRNA expression of Hmox-1, the gene encoding for heme oxygenase 1, without adversely affecting cell viability. Under all conditions, SSNO- appeared to be more potent than its parent compounds, NO and sulfide. SSNO- induced Nrf2 transactivation activity was abrogated by either NO scavenging with cPTIO or inhibition of thiol sulfuration by high concentrations of cysteine, implying a role for both persulfides/polysulfides and NO in SSNO- mediated Nrf2 activation. Taken together, our studies demonstrate that the Keap-1/Nrf2 redox system is a biological target of SSNO-, enriching the portfolio of bioactivity of this vasoactive molecule to also engage in the regulation of redox signaling processes. The latter suggests a possible role as messenger and/or mediator in cellular sensing and adaptations processes. PMID- 27663262 TI - Novel alpha-substituted tropolones promote potent and selective caspase-dependent leukemia cell apoptosis. AB - Tropolones, such as beta-thujaplicin, are small lead-like natural products that possess a variety of biological activities. While the beta-substituted natural products and their synthetic analogs are potent inhibitors of human cancer cell growth, less is known about their alpha-substituted counterparts. Recently, we synthesized a series of alpha-substituted tropolones including 2-hydroxy-7 (naphthalen-2-yl)cyclohepta-2,4,6-trien-1-one (alpha-naphthyl tropolone). Here, we evaluate the antiproliferative mechanisms of alpha-naphthyl tropolone and the related alpha-benzodioxinyl analog. The alpha-substituted tropolones inhibit growth of lymphocytic leukemia cells, but not healthy blood cells, with nanomolar potency. Treatment of leukemia cell lines with the tropolone dose-dependently induces apoptosis as judged by staining with annexin V and propidium iodide and Western blot analysis of cleaved caspase 3 and 7. Moreover, pre-treatment of cells with the caspase inhibitor Z-VAD-FMK inhibited the apoptotic effects of the tropolone in two lymphocytic lines. Caspase inhibition also blocked elevated histone acetylation caused by the tropolone, indicating that its effects on histone acetylation are potentiated by caspases. In contrast, alpha-naphthyl tropolone upregulated p53 expression and phosphorylation of Akt and mTOR in a manner that was not rescued by caspase inhibition. The effects of tropolone were blocked by co-incubation with high levels of free extracellular iron but not by pre-loading with iron. Additionally, dose and time dependent reduction in ex vivo viability of cells from leukemia patients was observed. Taken together, we demonstrate that alpha-substituted tropolones upregulate DNA damage repair pathways leading to caspase-dependent apoptosis in malignant lymphocytes. PMID- 27663264 TI - Surgical Results of Pure Endoscopic Endonasal Transsphenoidal Surgery for 331 Pituitary Adenomas: A 15-Year Experience from a Single Institution. AB - BACKGROUND: The aim of this study is to report the results of pure endoscopic endonasal transsphenoidal surgery (EETSS) for pituitary adenomas (PAs) and to evaluate the efficacy and safety of this procedure. In addition, we tried to determine the predicting factors for progression of PAs. METHODS: We reviewed the medical records of 331 consecutive patients who underwent pure EETSS of newly diagnosed PAs between April 1998 and December 2014. Demographic, endocrinologic, and radiologic features and their outcomes, complications, and hospital stay durations were retrospectively assessed in these patients. RESULTS: There were 157 (47.4%) nonfunctioning adenomas and 174 (52.6%) hormone-secreting adenomas. Fifty-one (15.4%) complications were present in 39 patients postoperatively. The frequent complications were temporary and permanent diabetes insipidus (14 and 3 cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (9 cases), and cerebrospinal fluid leaks (6 cases). There was only 1 death (0.3%) related to the procedure in this series. The patient's age (P = 0.047), the tumor size (P = 0.003), and the parasellar growth (P <0.001) were associated with the occurrence of complications on multivariate analysis. Progression occurred in 92 (27.8%) patients and the mean time-to-progression was 23.7 months (range, 3.7 52.4 months) after a mean follow-up period of 68.5 months. In the multivariate analysis, the tumor size (P = 0.021), the extent of surgery (P = 0.012), the Knosp classification (P = 0.002), and the MIB-1 index (P = 0.019) were associated with progression-free survival. The mean duration of hospitalization was 4.4 (+/ 1.6) days. CONCLUSIONS: The pure EETSS of PA provides acceptable and reasonable results representing a safe alternative procedure to the traditional transsphenoidal microscopic approach. PMID- 27663263 TI - Time Course of Symptomatic Recovery After Endoscopic Transsphenoidal Surgery for Pituitary Adenoma Apoplexy in the Modern Era. AB - BACKGROUND: Pituitary tumor apoplexy can result from either hemorrhagic or infarctive expansion of pituitary adenomas, and the related mass effect can result in compression of critical neurovascular structures. The time course of recovery of visual field deficits, headaches, ophthalmoparesis, and pituitary dysfunction after endoscopic transsphenoidal surgery has not been well established. METHODS: Medical records were retrospectively reviewed for all patients who underwent endoscopic transsphenoidal surgery for pituitary tumor apoplexy from April 2008 to November 2014. RESULTS: Of 578 patients who underwent transsphenoidal surgery, pituitary tumor apoplexy was identified in 44 patients (7.6%). Two patients had prior surgery, leaving 42 patients for final analysis. These included infarction-related apoplexy in 7 (14.4%) patients, and hemorrhagic apoplexy in 35 (85.6%) patients. Hemorrhagic adenomas had a larger axial tumor diameter than patients with infarctive adenomas (4.4 +/- 4.1 cm vs. 1.8 +/- 0.8 cm; P < 0.01), but were otherwise equivalent. At an average last follow-up of 2.52 years (range, 0.1-6.7 years), resolution of ophthalmoparesis as a result of pituitary tumor apoplexy demonstrated the longest recovery course (range, 2.4 +/- 2.2 months) compared with visual field deficits (range, 8.0 +/- 9.9 days), headaches (range, 1.9 +/- 3.0 days), or pituitary dysfunction (range, 2.0 +/- 1.8 weeks; P < 0.01). All patients who presented with headaches (n = 37) and/or visual disturbances (n = 22) had complete resolution of symptoms at last follow up, whereas 83.3% of patients who presented with ophthalmoplegia experienced resolution. Endocrinologic dysfunction remained relatively consistent after surgery. CONCLUSIONS: Endoscopic transsphenoidal surgery can provide durable resolution of symptoms for patients presenting with pituitary tumor apoplexy. Recovery from headaches, visual, and pituitary dysfunction may be more rapid compared with ophthalmoparesis. PMID- 27663265 TI - rapidGSEA: Speeding up gene set enrichment analysis on multi-core CPUs and CUDA enabled GPUs. AB - BACKGROUND: Gene Set Enrichment Analysis (GSEA) is a popular method to reveal significant dependencies between predefined sets of gene symbols and observed phenotypes by evaluating the deviation of gene expression values between cases and controls. An established measure of inter-class deviation, the enrichment score, is usually computed using a weighted running sum statistic over the whole set of gene symbols. Due to the lack of analytic expressions the significance of enrichment scores is determined using a non-parametric estimation of their null distribution by permuting the phenotype labels of the probed patients. Accordingly, GSEA is a time-consuming task due to the large number of required permutations to accurately estimate the nominal p-value - a circumstance that is even more pronounced during multiple hypothesis testing since its estimate is lower-bounded by the inverse number of samples in permutation space. RESULTS: We present rapidGSEA - a software suite consisting of two tools for facilitating permutation-based GSEA: cudaGSEA and ompGSEA. cudaGSEA is a CUDA-accelerated tool using fine-grained parallelization schemes on massively parallel architectures while ompGSEA is a coarse-grained multi-threaded tool for multi-core CPUs. Nominal p-value estimation of 4,725 gene sets on a data set consisting of 20,639 unique gene symbols and 200 patients (183 cases + 17 controls) each probing one million permutations takes 19 hours on a Xeon CPU and less than one hour on a GeForce Titan X GPU while the established GSEA tool from the Broad Institute (broadGSEA) takes roughly 13 days. CONCLUSION: cudaGSEA outperforms broadGSEA by around two orders-of-magnitude on a single Tesla K40c or GeForce Titan X GPU. ompGSEA provides around one order-of-magnitude speedup to broadGSEA on a standard Xeon CPU. The rapidGSEA suite is open-source software and can be downloaded at https://github.com/gravitino/cudaGSEA as standalone application or package for the R framework. PMID- 27663266 TI - Barriers to healthcare: Instrument development and comparison between autistic adults and adults with and without other disabilities. AB - Our objective was to use a community-based participatory research approach to identify and compare barriers to healthcare experienced by autistic adults and adults with and without other disabilities. To do so, we developed a Long- and Short-Form instrument to assess barriers in clinical and research settings. Using the Barriers to Healthcare Checklist-Long Form, we surveyed 437 participants (209 autistic, 55 non-autistic with disabilities, and 173 non-autistic without disabilities). Autistic participants selected different and greater barriers to healthcare, particularly in areas related to emotional regulation, patient provider communication, sensory sensitivity, and healthcare navigation. Top barriers were fear or anxiety (35% (n = 74)), not being able to process information fast enough to participate in real-time discussions about healthcare (32% (n = 67)), concern about cost (30% (n = 62)), facilities causing sensory issues 30% ((n = 62)), and difficulty communicating with providers (29% (n = 61)). The Long Form instrument exhibited good content and construct validity. The items combined to create the Short Form had predominantly high levels of correlation (range 0.2-0.8, p < 0.001) and showed responsiveness to change. We recommend healthcare providers, clinics, and others working in healthcare settings to be aware of these barriers, and urge more intervention research to explore means for removing them. PMID- 27663267 TI - Separation of novel phosphoproteins of Porphyromonas gingivalis using phosphate affinity chromatography. AB - Phosphorylation of serine, threonine and tyrosine is a central mechanism for regulating the structure and function of proteins in both eukaryotes and prokaryotes. However, the action of phosphorylated proteins present in Porphyromonas gingivalis, a major periodontopathogen, is not fully understood. Here, six novel phosphoproteins that possess metabolic activities were identified, namely PGN_0004, PGN_0375, PGN_0500, PGN_0724, PGN_0733 and PGN_0880, having been separated by phosphate-affinity chromatography. The identified proteins were detectable by immunoblotting specific to phosphorylated Ser (P Ser), P-Thr, and/or P-Tyr. These results imply that novel phosphorylated proteins might play an important role for regulation of metabolism in P. gingivalis. PMID- 27663268 TI - Fetal stomach and gallbladder in contact with the bladder wall is a common ultrasound sign of stomach-down left congenital diaphragmatic hernia. AB - PURPOSE: The aim of this study was to identify sonographic (US) findings that can assist in prenatal diagnosis of stomach-down left congenital diaphragmatic hernia (CDH), specifically related to positioning of the abdominal contents including the stomach, bladder, and gallbladder. METHODS: All US examinations with a postnatally confirmed diagnosis of stomach-down left CDH over a 13-year period were retrospectively reviewed for abnormal position of the abdominal contents, including whether the fetal stomach was in contact with the urinary bladder. Normal fetuses that underwent comprehensive US surveys were similarly evaluated for comparison in a 2:1 ratio. RESULTS: Twenty-two fetuses with stomach-down left CDH were identified in a cohort of 278 fetuses with left CDH. In 15/22 (68.2%) cases of stomach-down left CDH, the bladder and stomach walls were in contact. Contact of the fetal gallbladder with the fetal bladder wall was also observed and was present even more commonly (17/22 cases [77.3%]). There was no case of either the stomach or gallbladder in contact with the bladder wall in the normal fetal cohort (n = 44). CONCLUSIONS: Recognition of the fetal stomach and/or gallbladder in contact with the bladder wall can help in the detection of stomach down left CDH. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:8-13, 2017. PMID- 27663269 TI - How does specialist nursing contribute to HIV service delivery across England? AB - This study aimed to examine what specialist nursing contributes to HIV service delivery across England and how it could be optimised. A three part multi-method qualitative study was undertaken, involving (1) interviews with 19 stakeholders representing professional or service user groups; (2) interviews with nurse/physician pairs from 21 HIV services; and (3) case studies involving site visits to five services. A framework analysis approach was used to manage and analyse the data. There was substantial variability in specialist nursing roles and the extent of role development. Most hospital-based HIV nurses (13/19) were running nurse-led clinics, primarily for stable patients with almost half (6/13) also managing more complex patients. Role development was supported by non medical prescribing, a robust governance framework and appropriate workload allocation. The availability and organisation of community HIV nursing provision determined how services supported vulnerable patients to keep them engaged in care. Four service models were identified. The study showed that there is scope for providing a greater proportion of routine care through nurse-led clinics. HIV community nursing can influence health outcomes for vulnerable patients, but provision is variable. With limited financial resources, services may need to decide how to deploy their specialist nurses for best effect. PMID- 27663270 TI - Allosteric Regulation Points Control the Conformational Dynamics of the Molecular Chaperone Hsp90. AB - Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone responsible for the activation, maturation, and trafficking of several hundred client proteins in the cell. It is well known that (but not understood how) residues far away from Hsp90's nucleotide binding pocket can regulate its ATPase activity, a phenomenon called allosteric regulation. Here, the computational design of allosteric mutations was combined with in vitro and in vivo experiments to unravel nucleotide-responsive hot spots in the regulation of Hsp90. With this approach, we identified both activating and inhibiting regulation points and show that changes in those amino acids affect the conformational dynamics and ATPase activity of Hsp90 in vitro. Our observations that activating mutations loosen and inhibiting mutations rigidify the protein explain for the first time how Hsp90 changes in response to allosteric mutations. Additionally, mutations of these allosteric regulation points can be controlled by the interplay with Hsp90 co chaperones, thus providing cells with an efficient mechanism of modifying Hsp90's intrinsic properties via different layers of regulation. Altogether, our results show that a framework for transmitting conformational information exists in the Hsp90 structure. PMID- 27663271 TI - Structural Insights into the Inhibitory Mechanism of an Antibody against B7-H6, a Stress-Induced Cellular Ligand for the Natural Killer Cell Receptor NKp30. AB - Antibodies have been shown to block signaling through cell surface receptors using several mechanisms. The two most common are binding to the ligand-binding site of the receptor and, conversely, binding to the receptor-binding site of the ligand. Here, we investigated the inhibitory mechanism of an antibody (17B1.3) against human B7-H6, a stress-induced cellular ligand for the natural killer (NK) cell receptor NKp30. Binding of this antibody to B7-H6, a transmembrane protein expressed on tumor and other stressed cells, but not on normal cells, prevents NK cell activation via NKp30. We determined the crystal structure of antibody 17B1.3 in complex with the ectodomain of B7-H6 to 2.5A resolution. Surprisingly, 17B1.3 binds to a site on B7-H6 that is completely distinct from the binding site for NKp30, such that 17B1.3 does not block the NKp30-B7-H6 interaction. We then asked whether 17B1.3 prevents signaling by binding to a putative site for B7-H6 dimerization. However, structure-based mutations designed to disrupt potential B7 H6 dimerization through this site did not diminish NKp30-mediated cell activation. We conclude that the bulky 17B1.3 antibody most likely acts by sterically interfering with close cell-cell contacts at the NK cell-target cell interface that are required for NK cell activation. A similar inhibitory mechanism may apply to other antibodies, including therapeutic antibodies that block signaling through cell surface receptors whose ligands are also cell surface proteins. PMID- 27663273 TI - Retirement and Changes in Housework: A Panel Study of Dual Earner Couples. AB - Objectives: To examine how transitions to retirement influenced the division of household labor in dual earner couples. We tested hypotheses about changes (a) between a couple's preretirement and postretirement stage and (b) across the transitional phase during which both spouses retired. Method: We estimated fixed effects models for the effects of the husband's and the wife's retirement on changes in their hours and share of routine housework. The data came from 29 waves of the German Socio-economic Panel Study, comprising N = 31,040 annual observations of N = 3,288 dual earner couples aged 45 to 75 years. Results: Spouses who retired first performed more housework, whereas their partners who continued working performed less. This occurred irrespective of the retirement sequence. Husbands who retired first doubled up on their share of housework, but never performed more than 40% of a couple's total hours. None of the observed shifts were permanent. After both spouses had retired, couples reverted to their preretirement division of housework. Discussion: Although the findings on changes after retirement support the time availability hypothesis, gender construction theories still take precedence in explaining the division of household labor over the life course. PMID- 27663272 TI - C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis. AB - INTRODUCTION: The C9orf72 repeat expansion has been reported as a negative prognostic factor in amyotrophic lateral sclerosis (ALS). We have examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset. METHODS: C9orf72 status and demographic/clinical data from 4925 patients with ALS drawn from 3 prospective ALS registers (Ireland, Italy and the Netherlands), and clinical data sets in the UK and Belgium. Flexible parametric survival models were built including known prognostic factors (age, diagnostic delay and site of onset), gender and the presence of an expanded repeat in C9orf72. These were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data (IPD) meta-analysis was used to estimate HRs for results of particular importance. RESULTS: 457 (8.95%) of 4925 ALS cases carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival HR of 1.36 (1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion was being driven by spinal onset males (HR 1.56 (95% CI 1.25 to 1.96). CONCLUSIONS: This study represents the largest combined analysis of the prognostic characteristics of the C9orf72 expansion. We have shown for the first time that the negative prognostic implication of this variant is driven by males with spinal onset disease, indicating a hitherto unrecognised gender-mediated effect of the variant that requires further exploration. PMID- 27663275 TI - Neurologists win Ig Nobel prize for discovering that scratching the other side relieves itching. PMID- 27663276 TI - Hydration behaviors of calcium silicate-based biomaterials. AB - BACKGROUND/PURPOSE: Calcium silicate (CS)-based biomaterials, such as mineral trioxide aggregate (MTA), have become the most popular and convincing material used in restorative endodontic treatments. However, the commercially available CS based biomaterials all contain different minor additives, which may affect their hydration behaviors and material properties. The purpose of this study was to evaluate the hydration behavior of CS-based biomaterials with/without minor additives. METHODS: A novel CS-based biomaterial with a simplified composition, without mineral oxides as minor additives, was produced. The characteristics of this biomaterial during hydration were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectrometry. The hydration behaviors of commercially available gray and white MTAs with mineral oxide as minor additives were also evaluated for reference. RESULTS: For all three test materials, the XRD analysis revealed similar diffraction patterns after hydration, but MTAs presented a significant decrease in the intensities of Bi2O3-related peaks. SEM results demonstrated similar porous microstructures with some hexagonal and facetted crystals on the outer surfaces. In addition, compared to CS with a simplified composition, the FTIR plot indicated that hydrated MTAs with mineral oxides were better for the polymerization of calcium silicate hydrate (CSH), presenting Si-O band shifting to higher wave numbers, and contained more water crystals within CSH, presenting sharper bands for O-H bending. CONCLUSION: Mineral oxides might not result in significant changes in the crystal phases or microstructures during the hydration of CS-based biomaterials, but these compounds affected the hydration behavior at the molecular level. PMID- 27663277 TI - Rebound thymic hyperplasia following high dose chemotherapy and stem cell transplant in three neuroblastoma patients. PMID- 27663274 TI - Visualisation of Kiss1 Neurone Distribution Using a Kiss1-CRE Transgenic Mouse. AB - Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE-GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss-CRE heterozygous mice with CRE-activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80-90% of tdTomato positive neurones in the ARC were co-labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato-labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre-optic areas and to the lateral hypothalamus. PMID- 27663278 TI - Effect of nebivolol treatment during pregnancy on the intrauterine fetal growth, mortality and pup postnatal development in the l-NAME-induced hypertensive rats. AB - The present study was carried out to evaluate the effect of nebivolol vs. bisoprolol treatment on the intrauterine fetal growth, mortality and postnatal development in Nomega-Nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Hypertension was induced in normotensive pregnant Wistar rats by daily administration of l-NAME (100mg/kg/day, in the drinking water) for the period of pregnancy. After 9 days of l-NAME treatment, rats with systolic and diastolic blood pressure (SBP and DBP) more than 140/90mmHg were considered hypertensive. Then, some of them were treated from day 11 to day 18 of pregnancy with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) via oral gavage. SBP, DBP and heart rate (HR) were re-evaluated by tail cuff method on day 19 of pregnancy and morphometrical or histological studies were performed on day 20. In addition, the mortality and postnatal development of newborn pups were assessed in all groups. The l-NAME administration during pregnancy induced an increase in SBP and DBP while HR did not change. Nebivolol or bisoprolol treatment completely prevented the elevation of SBP and DBP induced by l-NAME with a reduction in HR in pregnant and non-pregnant rats. The intra-uterine fetal growth and the postnatal development of newborn rats in nebivolol-treated hypertensive group were significantly lower vs. control and higher vs. bisoprolol treated group with a higher mortality in the both types of treatments vs. control rats. The nebivolol and bisoprolol administration produce adverse effects on fetal growth and postnatal development, that limits their therapeutic use in females during pregnancy. PMID- 27663279 TI - Poly(ADP-ribose) polymerase is not involved in the neuroprotection exerted by azithromycin against ischemic stroke in mice. AB - Repurposing azithromycin has recently emerged as a promising strategy for the acute treatment of ischemic stroke. The mechanism of neuroprotection depends on the ability of this macrolide to promote polarization of microglia/macrophages towards beneficial M2 phenotypes. The immunomodulatory and anti-inflammatory effects of azithromycin, well documented in chronic inflammatory airway diseases, have been ascribed to the inhibition of the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1. Since these inflammatory transcription factors are positively regulated by poly(ADP-ribose) polymerase (PARP)-1, an enzyme actively involved in ischemic brain injury, we have investigated whether the neuroprotective properties of azithromycin in ischemic stroke involve upstream modulation of PARP-1. Administration of a single dose of this macrolide antibiotic upon reperfusion reduced, to a similar extent in wild type and PARP-1 knockout mice, infarct brain damage produced by transient occlusion of the middle cerebral artery. Moreover, we demonstrated the lack of effects of azithromycin on PARP-dependent death of HeLa cells, as well as on activity of purified PARP-1 and PARP-2. Thus, azithromycin protects mice against ischemic stroke injury through a mechanism independent of PARP activation. PMID- 27663280 TI - Pharmacokinetic-pharmacodynamic influence of N-palmitoylethanolamine, arachidonyl 2'-chloroethylamide and WIN 55,212-2 on the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice. AB - We evaluated the effects of ACEA (selective cannabinoid (CB)1 receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB1 and CB2 receptor agonist) and N palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy. PEA, ACEA or WIN intraperitoneal (i.p.) administration decreased the severity of tonic-clonic seizures. We also studied the effects of PEA, WIN or ACEA after co-administration with NIDA-41020 (CB1 receptor antagonist) or GW6471 (PPAR-alpha antagonist) and compared the effects of WIN, ACEA and PEA in order to clarify their mechanisms of action. PEA has anticonvulsant features in DBA/2 mice mainly through PPAR-alpha and likely indirectly on CB1 receptors, whereas ACEA and WIN act through CB1 receptors. The co-administration of ineffective doses of ACEA, PEA and WIN with some antiepileptic drugs (AEDs) was examined in order to identify potential pharmacological interactions in DBA/2 mice. We found that PEA, ACEA and WIN co administration potentiated the efficacy of carbamazepine, diazepam, felbamate, gabapentin, phenobarbital, topiramate and valproate and PEA only also that of oxcarbazepine and lamotrigine whereas, their co-administration with levetiracetam and phenytoin did not have effects. PEA, ACEA or WIN administration did not significantly influence the total plasma and brain levels of AEDs; therefore, it can be concluded that the observed potentiation was only of pharmacodynamic nature. In conclusion, PEA, ACEA and WIN show anticonvulsant effects in DBA/2 mice and potentiate the effects several AEDs suggesting a possible therapeutic relevance of these drugs and their mechanisms of action. PMID- 27663281 TI - Corosolic acid protects hepatocytes against ethanol-induced damage by modulating mitogen-activated protein kinases and activating autophagy. AB - The reactive oxygen species(ROS)/mitogen-activated protein kinase (MAPK) destroyed autophagy and the reactive oxygen species/mitogen-activated protein kinase (MAPK) pathway are considered closely related to ethanol-induced hepatocellular injury. Previous work indicated that corosolic acid, the natural extracts of leaves of the banaba tree, Lagerstroemia speciosa L., could protect the liver against ethanol-induced damage, but the underlying mechanism is unclear. In the study we found that corosolic acid significantly inhibited ethanol-induced apoptosis, increased level of tumor necrosis factor-alpha(TNF alpha) and reactive oxygen species accumulation in vitro. Corosolic acid inhibited ethanol-activated p38 and c-Jun N-terminal kinase MAPK signaling in BRL 3A and HepG2 cells as well as in experimental rats. Corosolic acid restored the ethanol-suppressed expression of autophagy-related genes, including beclin-1 and the ratio of microtubule-associated protein light chain 3II/I (LC3II/I) via AMP activated protein kinase (AMPK) activation both in vitro and in vivo. In experimental rats, corosolic acid ameliorated the detrimental histopathological findings. Corosolic acid may protect the liver against ethanol-induced injury by modulation of MAPK signaling and autophagy activation. These findings suggested that corosolic acid might be a promising agent in treatment of alcoholic liver diseases. PMID- 27663282 TI - Allergic rhinitis, rhinoconjunctivitis, and eczema: prevalence and associated factors in children. AB - OBJECTIVE: We aim to describe the data collected from India during phase 3 of the International study of asthma and allergy in childhood (ISAAC) study. Prevalence, severity, and population characteristics associated with rhinitis, rhinoconjunctivitis, and eczema were assessed. METHODS: Children from two age groups (6-7 and 13-14 years) were included in the study as per the ISAAC protocol. The symptoms of allergy and associated features were assessed using a questionnaire. RESULTS: The prevalence of allergic rhinitis among the 6-7 years age group was 11.3%, while it was 24.4% in the 13-14 years age group. The prevalence of allergic rhinoconjunctivitis was 3.9% in the 6-7 years age group and 10.9% in the 13-14 years age group. The prevalence of eczema was 2.8% in the 6-7 years age group and 3.7% in the 13-14 years age group. The passage of trucks near home, parental smoking, use of paracetamol, use of antibiotics, cooking with firewood, and television watching were associated with allergic rhinitis, rhinoconjunctivitis, and eczema. Maternal smoking was the strongest of all the associated features for allergic rhinitis, rhinoconjunctivitis, and eczema, especially in the 6-7 years age group (odds ratio: 1.9, 95% CI: 1.5-2.4; odds ratio: 2.9, 95% CI, 2.2-3.9; and odds ratio: 3.5, 95% CI: 2.6-4.8, respectively). CONCLUSION: Allergic conditions like allergic rhinitis, rhinoconjunctivitis, and eczema are prevalent among Indian children and are associated with environmental tobacco smoke, paracetamol use, antibiotic use, television watching, and outdoor and indoor air pollution. PMID- 27663283 TI - Travel health attitudes among Turkish business travellers to African countries. AB - BACKGROUND: The number of international travellers is increasing worldwide. Although health risks related to international travel are important and generally well-understood, the perception of these risks was unclear among Turkish travellers. We aimed to evaluate the attitudes and health risk awareness of Turkish travellers travelling to African countries. METHOD: A survey was performed of Turkish travellers bound for Africa from Istanbul International Ataturk Airport in July 2013. RESULTS: A total of 124 travellers were enrolled in the study. Among them, 62.9% had information about their destination but only 11.3% had looked for information on health problems related to travel and their destination. Of all travellers, 53.2% had at least one vaccination before travelling. The most commonly administered vaccine was for typhoid. Among the travellers, 69.3% and 80.6% had "no idea" about yellow fever vaccination and malaria prophylaxis, respectively. A positive correlation was found between a higher level of travellers' education and receiving the recommended vaccination for the destination. CONCLUSIONS: Our study revealed significant gaps in the vaccination and chemoprophylaxis uptake of Turkish travellers departing to Africa. An awareness and training program should be developed for travellers, as well as public health workers, to address health risks related to travel. PMID- 27663284 TI - Hajj 2016: Required vaccinations, crowd control, novel wearable tech and the Zika threat. PMID- 27663285 TI - Interleukin-1beta impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion. AB - Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion exhibits progressive white matter and cognitive impairments. However, its pathogenetic mechanisms are poorly understood. We investigated the role of interleukin-1beta (IL-1beta) and its receptor IL-1 receptor type 1 (IL 1R1) in an experimental SIVD model generated via right unilateral common carotid arteries occlusion (rUCCAO) in mice. We found that IL-1beta expression was elevated in the corpus callosum at the early stages after rUCCAO. IL-1 receptor antagonist (IL-1Ra), when delivered at an early stage, as well as IL-1R1 knockout, rescued the downregulation of myelin basic protein (MBP) and improved remyelination at the later stage after rUCCAO. Our data suggest that the recruitment of OPCs, but not the proliferation or differentiation of OPCs, is the only compromised step of remyelination following chronic cerebral ischemia. IL 1Ra treatment and IL-1R1 knockout had no effect on the oligodendrocyte progenitor cell (OPC) proliferation, but did promote the recruitment of newly generated OPCs to the corpus callosum, which can be reversed by compensatory expression of IL 1R1 in the SVZ of IL-1R1 knockout mice. Further, we found that recruited OPCs contribute to oligodendrocyte regeneration and functional recovery. In transwell assays, IL-1beta inhibited OPC migration through IL-1R1. Moreover, KdPT which can enter the brain to block IL-1R1 also showed comparable protection when intraperitoneally delivered. Our results suggest that IL-1beta during the early stages following chronic cerebral hypoperfusion impedes OPC recruitment via IL 1R1, which inhibits white matter repair and functional recovery. IL-1R1 inhibitors may have potential uses in the treatment of SIVD. PMID- 27663287 TI - Look into the crystal ball: Can vivid images of the future enhance physical health? AB - Many impulsive behaviors, unpleasant emotions, and misguided cognitions increase the incidence of type 2 diabetes and other conditions. This study tests the premise that such risk factors are inversely related to future clarity-the extent to which the future seems vivid and certain. Specifically, 211 participants completed the measures of future clarity and various determinants of health. Future clarity was positively associated with the inclination of participants to consume healthy food, abstain from cigarettes, participate in physical activity, and experience positive emotions. Future research should examine whether interventions designed to help individuals clarify and pursue their aspirations could stem lifestyle diseases. PMID- 27663286 TI - Acute high-grade acromioclavicular dislocations treated with triple button device (MINAR): Preliminary results. AB - OBJECTIVE: Describe the clinical and radiological results of triple button device in the treatment of high-grade AC dislocations (Rockwood, type V) and assess whether improves vertical and horizontal stability compared to the techniques previously described. MATERIAL AND METHODS: This retrospective study included 39 patients with type V acromioclavicular dislocations treated with Twin Tail TightRopeTM system (triple button device). Of the 39 patients, 33 (26 men and 7 women) were able to participate in clinical and radiographic follow up. At the time of surgery, the mean age was 25years+/-7(range, 17-49). All patients underwent bilateral-weighted Zanca (CC distance) and Alexander view (AC distance) as well as the Constant Score (CS) and Acromioclavicular Joint Instability Scoring System (ACJI). Radiological and clinical outcome was assessed during routine follow-up examinations preoperatively, postoperatively, 1, 3, 6 months and every year after the surgery. The presence of calcification, degenerative changes, mobilization of implants and bone resorption were also assessed. RESULTS: After a mean follow up of 25+/-4months (range 14-38), the results of the Constant (CS) were 94.1+/-5,5 (range 76-100) and test ACJI 87.3+/-9,8 (range 65 100), showing no significant differences with the uninjured shoulder (CS 95.8+/ 2.5, range 83-100; ACJI 94.1+/-3.7, range 80-100). At final review, we observed that preoperative coracoclavicular distance (Zanca View) improved from 21,75+/ 1.97mm to 8,73mm+/-0.75 and the acromioclavicular distance (Alexander View) from 12,65mm+/-1.99 to 0,35+/-0.3mm. Compared with healthy shoulder, these differences were not significant. There was no loss of reduction with this system in the vertical plane. 4 patients (12.12%) revealed signs of posterior instability with worse clinical test results. The presence of degenerative joint changes (6,06%), calcifications (27,2%) or mobilization of the implant (18,18%) was not associated with worse clinical outcomes. CONCLUSION: Twin Tail device using minimally invasive technique improves stability in the vertical and, specially in the horizontal plane relative to the previously described techniques without increasing number of complications. PMID- 27663288 TI - Psychological factors associated with diabetes self-management among adolescents with Type 1 diabetes: A systematic review. AB - This review aims to synthesise the literature examining the psychosocial variables related to self-management (insulin adherence, non-adherence and administration, blood sugar monitoring, dietary behaviour, exercise behaviour) in adolescents with type 1 diabetes. A systematic search of three electronic databases was carried out and, after the application of eligibility criteria, 21 articles were assessed for quality prior to data extraction. Numerous psychological factors were found to be associated with self-management; however, correlations were typically small to moderate. The strongest associations were found between social anxiety and diet (among males); greater intrinsic motivation, conscientiousness and diet; and extraversion and exercise. PMID- 27663289 TI - Reply to Bohleber and colleagues' paper on 'Unconscious phantasy'. PMID- 27663290 TI - Comments on Sandler, P.C. (2015). Commentary on "Transformations in Hallucinosis and the Receptivity of the Analyst" by Civitarese. PMID- 27663291 TI - Commentary on 'The case for neuropsychoanalysis'. PMID- 27663292 TI - On the argument for (and against) neuropsychoanalysis. PMID- 27663293 TI - How the impact of medication on psychoanalytic theory and treatment refutes Blass and Carmeli (2015). PMID- 27663294 TI - Response to Kessler, Sandberg, and Busch: The case for and against neuropsychoanalysis. PMID- 27663296 TI - Impact of hospital case-volume on subarachnoid hemorrhage outcomes: A nationwide analysis adjusting for hemorrhage severity. AB - OBJECTIVE: There have been suggestions that patients with subarachnoid hemorrhage (SAH) have a better outcome when treated in high-volume centers. Much of the published literature on the subject is limited by an inability to control for severity of SAH. METHODS: This is a nationwide retrospective cohort analysis using the Nationwide Inpatient Sample (NIS). The NIS Subarachnoid Severity Scale was used to adjust for severity of SAH in multivariate logistic regression modeling. RESULTS: The records of 47 911 414 hospital admissions from the 2006 2011 NIS samples were examined. There were 11 607 patients who met inclusion criteria for the study. Of these, 7787 (67.0%) were treated at a high-volume center compared with 3820 (32.9%) treated at a low-volume center. Patients treated at high-volume centers compared with low-volume centers were more likely to receive endovascular aneurysm control (58.5% vs 51.2%, P=.04), be transferred from another hospital (35.4% vs 19.7%, P<.01), be treated in a teaching facility (97.3% vs 72.9%, P<.01), and have a longer length of stay (14.9 days [interquartile range 10.3-21.7] vs 13.9 days [interquartile range, 8.9-20.1], P<.01). After adjustment for all baseline covariates, including severity of SAH, treatment in a high-volume center was associated with an odds ratio for death of 0.82 (95% confidence interval, 0.72-0.95; P<.01) and a higher odds of a good functional outcome (odds ratio, 1.16; 95% confidence interval, 1.04-1.28; P<.01). CONCLUSION: After adjustment for severity of SAH, treatment in a high-volume center was associated with a lower risk of in-hospital mortality and a higher odds of a good functional outcome. PMID- 27663297 TI - Precision and improving outcomes in acute kidney injury: Personalizing the approach. AB - It is now well over a decade since attempts at harmonization of acute renal failure into a definable entity termed acute kidney injury. This has led to several landmark studies outlining the epidemiology of acute kidney injury, particularly in the critically ill, as well as providing insights into the long term effects of the syndrome. Despite the introduction of consensus definitions and improvement in recognition, this has not been translated into outcome benefits as yet. The introduction of novel biomarkers associated with renal damage was primarily aimed at aiding early recognition of acute kidney injury. We argue that, in the future, using biomarkers may not only alert to acute kidney injury but may direct therapy in a personalized fashion rather than a one-size fits-all approach. PMID- 27663298 TI - Laminin alpha2-secreting fibroblasts enhance the therapeutic effect of skeletal myoblast sheets. AB - Objectives: Skeletal myoblast sheet (SMB) transplantation, a method used for treating failing hearts, results in the secretion of cytokines that improve heart function. Enhancing the survival rate of implanted myoblasts should yield more continuous and effective therapies. We hypothesized that laminin-211 (merosin), a major component of skeletal muscle extracellular matrix (ECM), which mediates cell-to-ECM adhesion by binding to alpha -dystroglycan ( alpha DG) on muscle cells, could inhibit detachment of implanted myoblasts from host myocardia. Methods: Multilayered sheets composed of fibroblasts expressing laminin G-module (LG)4-5 of alpha 2 and skeletal myoblasts were transplanted into ischemic cardiomyopathy model rats. Animals were divided into four groups: the ligation only (Control) group, and those transplanted with SMB alone, with both myoblasts and control fibroblast sheets (SMB + normal Fb), or with myoblasts and laminin alpha 2 LG4-5-expressing fibroblast sheets (SMB + laminin Fb). Results: Quantitative estimation of nebulin mRNA levels indicated that the transplanted myoblasts in SMB + laminin Fb group exhibited significantly higher survival rates than those in the other groups. Consistent with these findings, the myoblasts in SMB + laminin Fb group exhibited elevated expression of growth factors, while SMB + laminin Fb rats also showed significant improvements in percent fractional shortening (%FS) and left ventricular remodelling, compared to the other groups. Conclusions: Laminin secreted by implanted fibroblasts inhibited the detachment of implanted myoblasts from grafted myocardia, resulting in more permanent therapeutic effects upon myoblast sheet transplantation. PMID- 27663299 TI - 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. PMID- 27663300 TI - Norms, Attitudes, and Preferences: Responses to a Survey of Teens about Sexually Transmitted Infection and Pregnancy Prevention. AB - STUDY OBJECTIVE: To assess the values and beliefs regarding sexual behavior, sexual decision-making, and reproductive health learning preferences among teens in Hawaii. DESIGN: Survey regarding teens' knowledge, attitudes, and beliefs about sexual behaviors and preferences for learning about reproductive health. SETTING: University of Hawaii Department of Obstetrics and Gynecology clinics in Honolulu, Hawaii. PARTICIPANTS: Female patients and their male or female companions ages 14-19 years. INTERVENTIONS: A 30-question anonymous survey. MAIN OUTCOME MEASURES: The main outcome was to describe the norms, attitudes, beliefs, and preferences of teens in this setting with regard to sexual health and sexual health education. For this, we provide a description of response frequencies and a comparison of mean scores across demographic characteristics. RESULTS: We analyzed a total of 100 surveys. Teens endorsed more values and norms protective against sexually transmitted infection than those protective against pregnancy. Younger teens expressed more protective values as a result of the influence of perceived parental values, whereas older teens expressed less protective values on the basis of the influence of peers. Respondents expressed comfort talking with their clinician about sexual health, and also expressed a slight preference that their clinicians initiate these conversations. CONCLUSION: The influence of parental values and peer norms on sexual behavior must be taken into consideration when designing interventions to address adolescent sexual health. Additionally, teens' greater concern about the consequences of sexually transmitted infection could be leveraged by clinicians to initiate broader conversations about sexual health, and a variety of modalities, including online resources and in-person conversations, should be used to meet the diversity of preferences expressed by teens across demographic groups. PMID- 27663301 TI - Laparoscopic Outcomes of Adnexal Surgery in Older Children and Adolescents. AB - STUDY OBJECTIVE: To evaluate the outcomes of laparoscopic surgery for the treatment of adnexal pathology in older children and adolescents. DESIGN: A retrospective cohort review. SETTING: A tertiary academic center in Istanbul, Turkey. PARTICIPANTS: Pediatric and adolescent patients aged between 9 and 19 years (n = 69) who underwent laparoscopic surgery for adnexal pathology from January 2005 through September 2015. The patients who were pregnant or with non gynecologic pathology detected during surgery were excluded from the study. INTERVENTIONS: Patients were divided into 2 groups according to their age. Group 1 consisted of 31 patients aged between 9 and 16 years and group 2 included 38 patients aged between 17 and 19 years. MAIN OUTCOME MEASURES: The indication for surgery, procedures performed, anesthesia time, length of hospital stay, pathology findings, and complication rates were evaluated. RESULTS: Ovarian cystectomy and adnexal detorsion with or without cystectomy were the most frequently performed. Ovary-sparing conservative surgery was possible for all patients, except those with gonadal dysgenesis and testicular feminization (n = 6), who underwent laparoscopic gonadectomy. The most common pathologic finding was mature cystic teratoma (30.2%), followed by benign paratubal cyst, and simple cysts of the ovary. Anesthesia time was shorter in group 2 (P = .018). The procedures performed, length of hospital stay, complication rate, and pathology findings were not significantly different between the 2 groups. CONCLUSIONS: Laparoscopic surgery can be successfully performed as an efficient, safe, and well tolerated procedure for treating a wide variety of adnexal pathology among children and young adolescents without any significant variation between different age groups. PMID- 27663302 TI - Meaningful conversations in living with and treating chronic conditions: development of the ICAN discussion aid. AB - BACKGROUND: The needs of the growing population of complex patients with multiple chronic conditions calls for a different approach to care. Clinical teams need to acknowledge, respect, and support the work that patients do and the capacity they mobilize to enact this work, and to adapt and self-manage. Tools that enable this approach to care are needed. METHODS: Using user-centered design principles, we set out to create a discussion aid for use by patients, clinicians, and other health professionals during clinical encounters. We observed clinical encounters, visited patient homes, and dialogued with patient support groups. We then developed and tested prototypes in routine clinical practice. Then we refined a final prototype with extensive stakeholder feedback. RESULTS: From this process resulted the ICAN Discussion Aid, a tool completed by the patient and reviewed during the consultation in which patients classified domains that contribute to capacity as sources of burden or satisfaction; clinical demands were also classified as sources of help or burden. The clinical review facilitated by ICAN generates hypotheses regarding why some treatment plans may be problematic and may not be enacted in the patient's situation. CONCLUSION: We successfully created a discussion aid to elucidate and share insights about the capacity patients have to enact the treatment plan and hypotheses as to why this plan may or may not be enacted. Next steps involve the evaluation of the impact of the ICAN Discussion Aid on clinical encounters with a variety of health professionals and the impact of ICAN-informed treatment plans on patient-important outcomes. PMID- 27663304 TI - [Update on molecular classifications and new histological classification of bladder cancer]. AB - OBJECTIVE: Comment the new WHO histological classification of tumors of the urinary system and male genital organs 2016 and expose the state of art about urothelial carcinogenesis and molecular modifications of bladder cancer, with the consequences on the treatments. MATERIAL AND METHOD: A systematic review of the literature search was performed from the data base PubMed, focused on the following keywords: "bladder cancer", "molecular", "subtypes". RESULTS: The new WHO histological classification of tumors of the urinary system 2016 confirm the importance of pathology in determining the care of patients, especially the grade, the histological type and the infiltration, while taking into account the difficulties. In 2014, the Cancer Genome Atlas reported genetic modifications of bladder cancer. Recently, several studies explored molecular anomalies of bladder cancer and elaborated molecular classifications, analyzing their predictive value. According to the groups, different molecular subtype had been defined: Urobasal A, Urobasal B, genomically unstable, infiltrated, squamous cell carcinoma-like and p53-like luminal bladder cancers. This latter subgroup seems to be chemoresistant. CONCLUSIONS: The molecular biology and classifications allow a better understanding of bladder cancer and could complete in near future histological data to improve patient management. PMID- 27663303 TI - Mycoplasma ovipneumoniae induces sheep airway epithelial cell apoptosis through an ERK signalling-mediated mitochondria pathway. AB - BACKGROUND: Mycoplasma ovipneumoniae (M. ovipneumoniae) is a species of Mycoplasma bacteria that specifically infects sheep and goat, causing ovine infectious pleuropneumonia. However, the mechanism underlying the pathogen-host interaction between M. ovipneumoniae and airway epithelial cells is unknown. METHODS: A primary air-liquid interface (ALI) epithelial culture model generated from the bronchial epithelial cells of Ningxia Tan sheep (ovis aries) was employed to explore the potential mechanism of M. ovipneumoniae-induced cell apoptosis by characterizing the production of reactive oxygen species (ROS), methane dicarboxylic aldehyde (MDA) and anti-oxidative enzymes, as well as the mitochondrial membrane potentials, cytochrome C release, and activities of ERK and caspase signalling pathways. RESULTS: Increased ROS production and MDA concentration with mitochondrial membrane dysfunction and apoptotic cell death but decreased expression of the antioxidant enzymes catalase (CAT), glutathione synthetase (GSS), total superoxide dismutaes (T-SOD) and Mn-SOD were observed in sheep airway epithelial cells infected with M. ovipneumoniae. Mechanistically, the M. ovipneumoniae-induced cell apoptosis and disruption of mitochondrial integrity reflected mechanisms by which pathogen-activated mitogen-activated protein kinase (MAPK) signalling sequentially led to mitochondrial damage and release of Cyt-C into the cytoplasm, which in turn triggered the activation of caspase signalling cascade, resulting in the apoptosis of host cells. CONCLUSIONS: These results suggest that M. ovipneumoniae-induced ROS and MAPK signalling-mediated mitochondrial apoptotic pathways might play key roles in the pathogenesis of M. ovipneumoniae infection in sheep lungs. PMID- 27663305 TI - [An overview of French nurses' habits: Long-term urinary catheterization]. AB - INTRODUCTION: The lengthening of life expectancy associated with multiple comorbidities leads physicians and nurses to manage more and more patients with long-term urinary catheterization (LTUC). No recommendation is written about the management of LTUC patients. To assess the need to publish recommendations and tools to help nurses in a better management of LTUC, we conducted a survey of theoretical and practical knowledge of French nurses. MATERIALS AND METHODS: Epidemiological prospective study, type of practical studies in a declarative fashion, anonymous, made via computerized poll released on the website www.infirmiers.com. RESULTS: A total of 1254 registered nurses fulfilled the questionnaire. We observed a massive heterogeneity in different aspects of LTUC: local care and products used in them, urine bag change rhythm, lubrication of the catheter, respect of closed system, the rhythm of catheter change and in the management of blocked catheters. In total, 76% of nurses desire a theoretical and practical help for LTUC. CONCLUSION: We found a great diversity of knowledge and practices in terms of LTUC. In total, 40.67% of nurses realized at least a technical error during catheterization. To standardize the management of LTUC, we propose to draft recommendations under the aegis of the French Association of Urology. This will allow a better education of students, and providing online available support. PMID- 27663307 TI - [Efficacy and safety of flibanserin "new female Viagra(r)?": Literature review]. AB - INTRODUCTION: In August 2015, the US Food and Drug Administration (FDA) has approved Addyi(r) (flibanserin) for treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in pre-menopausal women. We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in women with HSDD. PATIENTS AND METHODS: A systematic literature review from the PubMed database search was carried out until April 2016 using the following keywords: "HSDD", "flibanserin", "sexual desire" and "ransomised controlled trial". RESULTS: We found four randomized double-blind control studies and two meta-analyzes and literature reviews. For the comparison of flibanserin with placebo, the results were reported in standardized mean difference (SMD). Regarding the main criterion "Satisfactory Sexual Event" (SSE), SMD was ranged from 0.49 to 1 (P<0.05); "Desire Sexual Score" SMD was ranged from 1.63 to 2.20 (P<0.05). For the Female Sexual Function Index (FSFI) desire domain score SMD was ranged from 0.03 to 0.4 (P<0.05). Adverse effects were mostly minor: dizziness and drowsiness. CONCLUSION: Flibanserin showed a moderate benefit in terms of frequency of sex and patient satisfaction. The long-term safety of flibanserin is still poorly defined and scientific data concerning this drug are still few. PMID- 27663306 TI - [Focus on molecular imaging in prostate cancer]. AB - INTRODUCTION: Prostate cancer is the most frequent cancer in men in France and it is a public health issue. This cancer is heterogenous. There is a clinical need of an accurate non-invasive imaging method to improve diagnosis, guide the choice of therapy and evaluate its efficacy. We undertook to critically review the different molecular imaging probes, currently used or in clinical trial. METHOD: A systematic review of the literature was performed in Pubmed/Medline database by searching for articles in French or English published on PET tracer in prostate cancer in clinical application. RESULTS: Several PET tracers are under investigation because of the low performance of the FDG in prostate cancer. In France, only two new PET tracers have the marketing authorization: the NaF and choline, but these tracers have several limitations. The NaF analyses only bone metastasis. The choline has changed the recurrence of prostate cancer but is not effective for recurrence with low PSA, furthermore its sensitivity is low for the detection of lymph nodes metastasis in initial disease. Several tracers in trial including the PSMA offer encouraging prospects in initial staging and for recurrences. CONCLUSION: An accurate knowledge in molecular biology allowed to develop the metabolic imagery. Many new tracers are under evaluation in prostate cancer. The indication of each of them needs to be established. PMID- 27663308 TI - Health research priority setting in Zambia: a stock taking of approaches conducted from 1998 to 2015. AB - BACKGROUND: Priority setting in health research is an emerging field. In Zambia, like many other African countries, various priority setting activities have been undertaken with a view to identify research activities to which the available resources can be targeted while at the same time maximising the health impact for resource allocation to support evidence-based decision-making. The aim of this paper is to document the key elements of the various priority setting activities that have been conducted since 1998, identifying the key lessons and providing recommendations to improve the process. METHODS: A comprehensive review of the previous priority setting activities and processes in Zambia was conducted. Both published and unpublished reports were reviewed in order to identify any research priority setting processes that have been undertaken in Zambia. We developed a framework, based on the priority setting literature, to guide our abstraction and synthesis of the literature. RESULT: The earliest record of priority setting was conducted in 1998. Various priority setting approaches have been implemented in Zambia; ranging from externally driven, once-off activities to locally (in country) initiated comprehensive processes. However, there has been no systematic national process for priority setting. These priority setting processes in Zambia were characterised by limited stakeholder buy-in of the resulting national research or programmatic research agenda. Most striking was the lack of linkages between the different initiatives. There seems to have been no conscious recognition and building on previous priority-setting experiences of previous initiatives. CONCLUSION: There were gaps in the priority setting processes, stakeholder engagement and application of a defined criterion. There is a need for a priority setting framework coupled with local capacity developed across a range of stakeholders. PMID- 27663309 TI - Antifungal prophylaxis of patients undergoing allogenetic hematopoietic stem cell transplantation in China: a multicenter prospective observational study. AB - BACKGROUND: Antifungal prophylaxis is currently regarded as the gold standard in situations with allo-genetic hematopoietic stem cell transplantation (allo-HSCT). However, the epidemiological information regarding prophylaxis of invasive fungal diseases (IFDs) is not clear in China. METHODS: We report the first large-scale (1053 patients) observational study of the prophylaxis and management of IFDs among patients with allo-HSCT in China. RESULTS: The incidence rates of IFD after primary antifungal prophylaxis (PAP), secondary antifungal prophylaxis (SAP), and non-prophylaxis were 22.7 vs. 38.6 vs. 68.6 %, respectively (P = 0.0000). The median time from transplantation to IFD was 45 days in PAP patients, 18 days in SAP patients, and 12 days in non-prophylaxis patients. Aspergillus spp. represents the most common type of fungal infection. Independent risk factors for IFD in allo-HSCT patients with PAP were age, having human leukocyte antigen (HLA) haploidentical or matched unrelated donor, decreased albumin levels, and the use of itraconazole as the prophylactic antifungal agent. Among SAP transplant recipients, there was no significant risk factor for IFDs. The incidence rates of overall survival (OS) in the PAP, SAP, and no prophylaxis groups were 85.07, 78.80, and 74.82, respectively (P = 0.01). CONCLUSIONS: This observational study indicates that prophylaxis of IFD is helpful to reduce the incidence of IFDs and improve the OS of patients after allo-HSCT. PMID- 27663311 TI - Picture of 'complete contusion'. AB - One in five health authorities failed to balance their budgets by the Government's April 1 deadline, a national survey revealed on the eve of the NHS reforms. PMID- 27663312 TI - Unions welcome nurses on health watchdog. AB - Nursing unions have welcomed the strong representation for the profession on the new health services watchdog, announced last week by Health Secretary, William Waldegrave. PMID- 27663313 TI - Bank nurses. AB - Nurses who 'moonlight'as bank staff in the hospitals where they also have fulltime jobs are sometimes working 12 or even 24-hour shifts at a time, it was claimed last week. PMID- 27663310 TI - Major influence of repetitive elements on disease-associated copy number variants (CNVs). AB - Copy number variants (CNVs) are important contributors to the human pathogenic genetic diversity as demonstrated by a number of cases reported in the literature. The high homology between repetitive elements may guide genomic stability which will give rise to CNVs either by non-allelic homologous recombination (NAHR) or non-homologous end joining (NHEJ). Here, we present a short guide based on previously documented cases of disease-associated CNVs in order to provide a general view on the impact of repeated elements on the stability of the genomic sequence and consequently in the origin of the human pathogenic variome. PMID- 27663315 TI - ? AB - Bygone birth: Staff at Liverpool's oldest maternity hospital, Mill Road, dressed in historic style to mark the hospital's centenary. Staff nurse Lindsey Cleworth is pictured with one of the newest arrivals, Lawrence Marsden. PMID- 27663314 TI - Super-union foresees membership for RCN. AB - The Royal College of Nursing may one day be invited 'into the family' created by the new public sector 'super-union', COHSE General Secretary Hector MacKenzie said last week. PMID- 27663316 TI - GP Contracts. AB - Practice nurses' time is being wasted because the GP contract requires them to offer screening to elderly patients who are already being cared for by district nurses, it was claimed last week at the end of the contract's first year. PMID- 27663318 TI - ? AB - Head case: One of the wax models on display at Guy's Hospital's Gordon Museum in London which is under threat of closure through lack of funds. PMID- 27663317 TI - Waldegrave says nurses may jump Trust queues. AB - Hospital Trusts may allow nurses to jump waiting lists for fast treatment, Health Secretary William Waldegrave declared last week. PMID- 27663319 TI - National lottery. AB - More than half the population are in favour of a national lottery provided it raises money for the NHS, a new survey shows. PMID- 27663320 TI - Labour market study scheduled for June release. AB - The draft report from a major study into the labour market for health care staff in London is expected at the end of June, says the Institute of Manpower Studies. The report has been commissioned by the King's Fund and will provide the basis of a strategy for the future of acute health services in London. PMID- 27663321 TI - Twenty-five per cent of appeals successful. AB - More than a quarter of clinical grading appeals heard at regional level have been upheld, Junior Health Minister Stephen Dorrell told the Commons last w'eek. PMID- 27663322 TI - Elderly people missing care reforms information. AB - Eighty per cent of the elderly have not heard of the Government's White Paper 'Care in the Community', according to the results of a study undertaken by the National Carers' Survey. PMID- 27663323 TI - Energy efficiency targets encouraged. AB - The NHS could reduce its energy consumption by 15 per cent through energy efficiency measures, the Audit Commission said last week. PMID- 27663325 TI - ? AB - Nursing staff from the psychiatric hospital on the Greek island of Leros spent time at Ottershaw Hospital. Surrey, last week as part of their visit to study nursing practice in the UK. Poor conditions at Leros were highlighted in reports last year. PMID- 27663327 TI - Prior experience plays a part in nursing strategy. AB - Assessment of prior experiential learning should form part of any strategy to combat the effects of the demographic time bomb on nursing, according to Norman Evans, Director of the Learning from Experience Trust, a group set up to help people make maximum use of their knowledge and skills. PMID- 27663326 TI - Minister gives assurances on nurses' important role. AB - Delegates to the second International Mental Handicap Conference in Edinburgh have been assured by the Scottish Health Minister that the mental handicap nursing profession will continue to play an important role in providing care to its clients in a wide range of hospital and community settings. PMID- 27663328 TI - Inter-dependent role for the profession. AB - The nursing profession is slowly realising that its role is inter-dependent with that of medicine, Professor George Castle- dine, Head of the Department of Nursing and Community Health at Birmingham Polytechnic, told the conference. PMID- 27663329 TI - Nurses' attitudes towards employers must change. AB - Nurses' attitudes to their employers and colleagues are contrary to the notions proposed in the United Kingdom Central Council's Post Registration Education and Practice Project, Royal College of Nursing President Professor June Clarke said last week. PMID- 27663330 TI - Parliament. AB - Nursing is completelyunrepresented on the boards of the new self-governing NHS Trusts, Shadow Health Secretary Robin Cook has revealed. His examination of the first 57 'opted-out' trusts shows that the overwhelming majority of more than 300 chairmen and directors have business backgrounds, usually with no NHS connections whatsoever. PMID- 27663331 TI - World news. AB - Philippines Health workers are among more than 50 people who arc reported to have 'disappeared' in the Philippines last year. Most of them are alleged critics or opponents of the government and at least five are believed to have died while in custody. Others appear to have been torutured, a report from Amnesty International states. PMID- 27663333 TI - Parkinson's disease and communication. AB - Distress, frustration and anxiety caused by poor communication between nurses and patients with Parkinson's disease can worsen symptoms, according to a new information pack produced by the Parkinson's Disease Society (PDS). PMID- 27663334 TI - ? AB - High animal fat consumption may contribute to narrowing of the arteries: fatty deposits develop into plaques filled with cholesterol as in this section of human aorta. Hardening and thickening of arteries is a major cause of death. PMID- 27663335 TI - Educating people to the dangers of CHD. AB - Coronary heart disease (CHD) caused over 130,000 deaths in England and Wales in 1989, and its treatment costs the National Health Service L500 million annually. PMID- 27663337 TI - Listings. PMID- 27663336 TI - Link between chronic psychosis and 'ecstasy'. AB - The drug 'ecstasy' can cause chronic psychosis after heavy use, according to researchers at Kings College Hospital and the Maudsley Hospital in south London. PMID- 27663338 TI - Nurse turned consumerLearning to live with the devastating effects of emphysema led former RCN General Secretary' Trevor Clay to set up a support group. this week he takes on the role of president of a new club for people with long-term lung problems, breathe easy. Nursing Standard Editor Norah Casey talked to him about the condition and the effect it has had on his life and career. AB - Every 60 minutes a small alarm sounds on Trevor Clay's watch. 'Time is precious to me now. I like to know when each new hour begins,' he tells me, as we drive through the hot Californian desert. PMID- 27663339 TI - Follow the reader. AB - Underfunded libraries are threatening , the very success of Project 2000 courses and the crisis is set to worsen after the Government's decision not to inject more cash into nursing libraries, a new study reveals. PMID- 27663340 TI - Relating practical experiments to theory. AB - Integrating theory into practice is not without its difficulties. Often concepts derived from the physical and behavioural sciences appear to be unrelated to nursing practice and although noted laboriously by student nurses no active learning occurs. As nurse education changes not only in curriculum content and teaching methodology but in who will do the teaching and in what venue, then the importance of ensuring the relevance of theoretical concepts to nursing practice will increase. PMID- 27663341 TI - Project 2000 paper tigers. AB - I am a second-year RMN student, and also the chair of the Learners' Council at my school of nursing. PMID- 27663342 TI - Don't leave us out in the cold. AB - I am currently employed as an auxiliary nurse and have just found out that for some strange reason we cannot become RCN members, which I feel is wrong. PMID- 27663344 TI - Counselling relief. AB - I sighed with relief when I read how counselling helped a nurse resolve 20 years of buried grief (Points of View, Nursing Standard February 27). Someone else has felt like I have. PMID- 27663343 TI - Seal of approval? AB - On attending an extended role of the nurse course at Plymouth I was given a revised policy of the 1977 guidance (HC(77)22) on 'The extending role of the nurse' to find paragraph 5.3 reads as follows. PMID- 27663345 TI - St George's reunion. AB - I would like to contact nurses from the 1961 set of St George's Hospital, London. PMID- 27663347 TI - ? PMID- 27663346 TI - Information exchange. AB - I am a staff nurse on an outpatients department in I Peterborough, and have just completed a counselling ' course. I have been asked to set up a counselling service with neurology patients and their carers. PMID- 27663348 TI - Nurse's Guide for IV Medications Valerand A and Nurse's Guide for IV Medications Deglin J , editors F A Davis 528pp L13.50 0-8036-8840-7 [Formula: see text]. AB - The giving of intravenous medications can be a minefield for nurses. Nurse's Guide for IV Medications, written by nurses and pharmacists specifically for nurses, promises much. At first glance, it seems overwhelming with so much information crammed into such a small space. PMID- 27663350 TI - Keepers Glouberman S Keepers King's Fund 148pp L9.95 1-85551-065-0 [Formula: see text]. AB - The 'keepers' of the title of Sholom Glouberman's revealing book are all workers in closed institutions, and through a series of interviews they tell of their struggles to avoid becoming no more than part of the furniture in their places of work. PMID- 27663351 TI - Giaxo competition. AB - Get writing now for this year's Glaxo/ Nursing Standard Student Essay award, which will include a special prize of free attendance at the RCN Cancer Nursing Society's annual conference in York. PMID- 27663352 TI - Patti Sheeks. AB - Dear Patti, I am writing for your opinion on PREPP. The United Kingdom Central Council's Post- Registration Education and Practice Project, which is now out for consultation. PMID- 27663354 TI - Epidemiological aspects of rotavirus and adenovirus in hospitalized children with diarrhea: a 5-year survey in Beijing. AB - BACKGROUND: Diarrhea caused by viruses is a global problem among young children. We investigated two of the most important agents, rotavirus and adenovirus, to provide epidemiological evidence for a better understanding of their role among children with acute diarrhea. METHODS: A total of 3147 hospitalized children were enrolled in the study during 2010 ~ 2014. Antigen testing for rotavirus and DNA testing for adenovirus were performed on stool specimens collected from participants. RESULTS: There were 1985 cases of community-acquired diarrhea (CAD) and 1162 cases of hospital-acquired diarrhea (HAD). A total of 692 cases (22.0 %) were positive for rotavirus. Rotavirus was detected in more children with HAD than in those with CAD (24.6 %; 286/1162 vs. 20.5 %; 406/1985). A total of 324 cases (10.3 %) were adenovirus positive. There was a significant difference between the CAD group and HAD group (9.5 %; 188/1985 vs. 11.7 %; 136/1162: chi 2 = 3.957, p = 0.047). Co-infection was found in only 35 children (1.11 %), and the co-infection rate was similar between the CAD and HAD groups (chi 2 = 1.174, p = 0.279). There was no association between sex and the detection rate of these viruses. The positive rate was significantly different for rotavirus among CAD cases (chi 2 = 27.979, p < 0.001) and for adenovirus (chi 2 = 34.362, p < 0.001) in the five age groups. Compared with the other four age groups (15.8-19.8 %), the prevalence of rotaviruses was highest among children aged 12-24 months (28.6 %). Adenovirus was detected in 3.6 % of neonates compared with 5.8 % of infants from 1 to 6 months old; this increased to 12.0-13.8 % in children over 6 months of age. In HAD cases, age differences were not found for rotavirus and adenovirus. Seasonal variation of rotavirus was observed, with peaks in November and December and with through in July and August; however, no clear seasonal pattern was found for adenovirus. CONCLUSION: Detection rates for rotavirus and adenovirus were significantly higher in children with HAD than those with CAD, but co-infection was very low. A high prevalence of rotavirus was identified in neonates with diarrhea. Vaccination for rotavirus gastroenteritis should be considered in neonates. PMID- 27663353 TI - Characterization of Irreversible Electroporation Ablation with a Validated Perfused Organ Model. AB - PURPOSE: To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies. MATERIALS AND METHODS: Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 usec), number of pulses (50-600), electrode exposure (1.0-2.0 cm), and electrode spacing (1.5-2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers. RESULTS: Ablation dimensions in the perfused model correlated well with corresponding in vivo ablations (R2 = 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200-600 pulses (3.2 mm +/- 3.8 width and 5.2 mm +/- 3.9 height). CONCLUSIONS: The perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy. PMID- 27663355 TI - Brain imaging and cognition in young narcoleptic patients. AB - The relationship between functional brain images and performances in narcoleptic patients and controls is a new field of investigation. We studied 71 young, type 1 narcoleptic patients and 20 sex- and age-matched control individuals using brain positron emission tomography (PET) images and neurocognitive testing. Clinical investigation was carried out using sleep-wake evaluation questionnaires; a sleep-wake study was conducted with actigraphy, polysomnography, multiple sleep latency test (MSLT), and blood tests (with human leukocyte antigen typing). The continuous performance test (CPT) and Wisconsin card sorting test (WCST) were administered on the same day as the PET study. PET data were analyzed using Statistical Parametric Mapping (version 8) software. Correlation of brain imaging and neurocognitive function was performed by Pearson's correlation. Statistical analyses (Student's t-test) were conducted with SPSS version-18. Seventy-one narcoleptic patients (mean age: 16.15 years, 41 boys (57.7%)) and 20 controls (mean age: 15.1 years, 12 boys (60%)) were studied. Results from the CPT and WCST showed significantly worse scores in narcoleptic patients than in controls (P < 0.05). Compared to controls, narcoleptic patients presented with hypometabolism in the right mid-frontal lobe and angular gyrus (P < 0.05) and significant hypermetabolism in the olfactory lobe, hippocampus, parahippocampus, amygdala, fusiform, left inferior parietal lobe, left superior temporal lobe, striatum, basal ganglia and thalamus, right hypothalamus, and pons (P < 0.05) in the PET study. Changes in brain metabolic activity in narcoleptic patients were positively correlated with results from the sleepiness scales and performance tests. Young, type 1 narcoleptic patients face a continuous cognitive handicap. Our imaging cognitive test protocol can be useful for investigating the effects of treatment trials in these patients. PMID- 27663356 TI - Evaluation of upper extremity neurorehabilitation using technology: a European Delphi consensus study within the EU COST Action Network on Robotics for Neurorehabilitation. AB - BACKGROUND: The need for cost-effective neurorehabilitation is driving investment into technologies for patient assessment and treatment. Translation of these technologies into clinical practice is limited by a paucity of evidence for cost effectiveness. Methodological issues, including lack of agreement on assessment methods, limit the value of meta-analyses of trials. In this paper we report the consensus reached on assessment protocols and outcome measures for evaluation of the upper extremity in neurorehabilitation using technology. The outcomes of this research will be part of the development of European guidelines. METHODS: A rigorous, systematic and comprehensive modified Delphi study incorporated questions and statements generation, design and piloting of consensus questionnaire and five consensus experts groups consisting of clinicians, clinical researchers, non-clinical researchers, and engineers, all with working experience of neurological assessments or technologies. For data analysis, two major groups were created: i) clinicians (e.g., practicing therapists and medical doctors) and ii) researchers (clinical and non-clinical researchers (e.g. movement scientists, technology developers and engineers). RESULTS: Fifteen questions or statements were identified during an initial ideas generation round, following which the questionnaire was designed and piloted. Subsequently, questions and statements went through five consensus rounds over 20 months in four European countries. Two hundred eight participants: 60 clinicians (29 %), 35 clinical researchers (17 %), 77 non-clinical researchers (37 %) and 35 engineers (17 %) contributed. At each round questions and statements were added and others removed. Consensus (>=69 %) was obtained for 22 statements on i) the perceived importance of recommendations; ii) the purpose of measurement; iii) use of a minimum set of measures; iv) minimum number, timing and duration of assessments; v) use of technology-generated assessments and the restriction of clinical assessments to validated outcome measures except in certain circumstances for research. CONCLUSIONS: Consensus was reached by a large international multidisciplinary expert panel on measures and protocols for assessment of the upper limb in research and clinical practice. Our results will inform the development of best practice for upper extremity assessment using technologies, and the formulation of evidence-based guidelines for the evaluation of upper extremity neurorehabilitation. PMID- 27663357 TI - Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers. AB - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumours with a typical 5 year survival rate of <40 %. DNA methylation in tumour-suppressor genes often occurs at an early stage of tumorigenesis, hence DNA methylation can be used as an early tumour biomarker. Saliva is an ideal diagnostic medium to detect early HNSCC tumour activities due to its proximity to tumour site, non-invasiveness and ease of sampling. We test the hypothesis that the surveillance of DNA methylation in five tumour-suppressor genes (RASSF1alpha, p16 INK4a , TIMP3, PCQAP/MED15) will allow us to diagnose HNSCC patients from a normal healthy control group as well as to discriminate between Human Papillomavirus (HPV)-positive and HPV-negative patients. METHODS: Methylation specific PCR (MSP) was used to determine the methylation levels of RASSF1alpha, p16 INK4a , TIMP3 and PCQAP/MED15 in DNA isolated from saliva. Statistical analysis was carried out using non-parametric Mann-Whitney's U-test for individually methylated genes. A logistic regression analysis was carried out to determine the assay sensitivity when combing the five genes. Further, a five-fold cross-validation with a bootstrap procedure was carried out to determine how well the panel will perform in a real clinical scenario. RESULTS: Salivary DNA methylation levels were not affected by age. Salivary DNA methylation levels for RASSF1alpha, p16 INK4a , TIMP3 and PCQAP/MED15 were higher in HPV-negative HNSCC patients (n = 88) compared with a normal healthy control group (n = 122) (sensitivity of 71 % and specificity of 80 %). Conversely, DNA methylation levels for these genes were lower in HPV-positive HNSCC patients (n = 45) compared with a normal healthy control group (sensitivity of 80 % and specificity of 74 %), consistent with the proposed aetiology of HPV-positive HNSCCs. CONCLUSIONS: Salivary DNA tumour-suppressor methylation gene panel has the potential to detect early-stage tumours in HPV-negative HNSCC patients. HPV infection was found to deregulate the methylation levels in HPV-positive HNSCC patients. Large-scale double-blinded clinical trials are crucial before this panel can potentially be integrated into a clinical setting. PMID- 27663358 TI - Unused opioid analgesics and drug disposal following outpatient dental surgery: A randomized controlled trial. AB - BACKGROUND: Individuals who abuse prescription opioids often use leftover pills that were prescribed for friends or family members. Dental surgery has been identified as a common source of opioid prescriptions. We measured rates of used and unused opioids after dental surgery for a pilot program to promote safe drug disposal. METHODS: We conducted a randomized controlled trial of opioid use patterns among patients undergoing surgical tooth extraction at a university affiliated oral surgery practice. The primary objective was to describe opioid prescribing and consumption patterns, with the number of unused opioid pills remaining on postoperative day 21 serving as the primary outcome. The secondary aim was to measure the effect of a behavioral intervention (informing patients of a pharmacy-based opioid disposal program) on the proportion of patients who disposed or reported intent to dispose of unused opioids. (NCT02814305) Results: We enrolled 79 patients, of whom 72 filled opioid prescriptions. On average, patients received 28 opioid pills and had 15 pills (54%) left over, for a total of 1010 unused pills among the cohort. The behavioral intervention was associated with a 22% absolute increase in the proportion of patients who disposed or reported intent to dispose of unused opioids (Fisher's exact p=0.11). CONCLUSION: Fifty-four percent of opioids prescribed in this pilot study were not used. The pharmacy-based drug disposal intervention showed a robust effect size but did not achieve statistical significance. Dentists and oral surgeons could potentially reduce opioid diversion by moderately reducing the quantity of opioid analgesics prescribed after surgery. PMID- 27663359 TI - Rheumatology training experience across Europe: analysis of core competences. AB - BACKGROUND: The aim of this project was to analyze and compare the educational experience in rheumatology specialty training programs across European countries, with a focus on self-reported ability. METHOD: An electronic survey was designed to assess the training experience in terms of self-reported ability, existence of formal education, number of patients managed and assessments performed during rheumatology training in 21 core competences including managing specific diseases, generic competences and procedures. The target population consisted of rheumatology trainees and recently certified rheumatologists across Europe. The relationship between the country of training and the self-reported ability or training methods for each competence was analyzed through linear or logistic regression, as appropriate. RESULTS: In total 1079 questionnaires from 41 countries were gathered. Self-reported ability was high for most competences, range 7.5-9.4 (0-10 scale) for clinical competences, 5.8-9.0 for technical procedures and 7.8-8.9 for generic competences. Competences with lower self reported ability included managing patients with vasculitis, identifying crystals and performing an ultrasound. Between 53 and 91 % of the trainees received formal education and between 7 and 61 % of the trainees reported limited practical experience (managing <=10 patients) in each competence. Evaluation of each competence was reported by 29-60 % of the respondents. In adjusted multivariable analysis, the country of training was associated with significant differences in self-reported ability for all individual competences. CONCLUSION: Even though self-reported ability is generally high, there are significant differences amongst European countries, including differences in the learning structure and assessment of competences. This suggests that educational outcomes may also differ. Efforts to promote European harmonization in rheumatology training should be encouraged and supported. PMID- 27663360 TI - Determination of linear and cyclic volatile methylsiloxanes in blood of turtles, cormorants, and seals from Canada. AB - We measured the concentrations of linear and cyclic volatile methylsiloxanes (VMS) concentrations in the blood plasma of turtles, cormorants, and seals collected from Canadian freshwater and marine ecosystems. A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was developed to quantify the levels of linear and cyclic VMS in the plasma samples. The cyclic VMS of hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) were present in the plasma of all three species. Linear VMS compounds were observed only in seal plasma from one contaminated site. There was no statistically significant difference among species and locations for D3, D4, and D6 concentrations. Average D5 concentrations ranged from 0.143 to 7.39ngg-1; these concentrations appeared to be associated with diffuse/urban sources. Snapping turtles, cormorants, and seals all exhibited elevated D5 concentrations in contaminated sites relative to the reference sites. Our data indicate that local urban sources of VMS contributed significantly to the observed D5 concentrations in free-ranging wildlife. The presence of cyclic VMS in the plasma of the three species from Canada demonstrates that these chemicals are ubiquitous in aquatic biological systems. This finding raises concerns regarding their persistence in freshwater and marine environments. To the best of our knowledge, this study reports the first measurements of VMS compounds in the plasma of reptiles, birds, and mammals. PMID- 27663362 TI - Imaging Findings of Intraluminal Duodenal Duplication Cyst in a Pediatric Patient. PMID- 27663361 TI - 5-aza-2'-deoxycytidine Inhibits the Proliferation of Lung Fibroblasts in Neonatal Rats Exposed to Hyperoxia. AB - BACKGROUND: A persistent increase in the number of lung fibroblasts (LFs) is found in the interstitium of the lungs of infants with bronchopulmonary dysplasia (BPD), which leads to lung fibrosis. P16 methylation plays an important role in the pathogenesis of BPD. 5-aza-2'-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. This study investigated the effects of 5 aza-CdR on LFs in vitro from a hyperoxia-induced lung fibrosis model in newborn rats. METHODS: Methylation-specific polymerase chain reaction (PCR) and Western blotting were performed to determine P16 gene methylation status and protein expression after LFs were treated with 0 MUmol/L, 0.5 MUmol/L, 1.0 MUmol/L, and 5.0 MUmol/L 5-aza-CdR for 120 hours. Proliferation was assessed by an MTT assay after LFs were treated with 0 MUmol/L, 0.5 MUmol/L, 1.0 MUmol/L, and 5.0 MUmol/L 5-aza-CdR for 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. At the final time point, cells were also analyzed by flow cytometry to identify any change in their cell cycle profiles. RESULTS: A methylated P16 gene promoter was detected in hyperoxia LFs. Following treatment with 5-aza-CdR, partial methylation and demethylation was detected. The expression protein's level of the P16 gene was significantly higher in the 5.0 MUmol/L 5-aza-CdR-treated group compared with that in the control group (p < 0.01). The cell growth rate at each tested time point was lower in the 5-aza-CdR-treated group compared with that in the control group after 72 hours (p < 0.01). Flow cytometry revealed that the cells in the 1.0 MUmol/L and 5.0 MUmol/L 5-aza-CdR-treated groups were apparently arrested in the G0/G1 phase and that the number of cells in the S phase was significantly lower than the control group (p < 0.01). CONCLUSION: 5-aza-CdR inhibits the growth of the LFs in hyperoxia-induced neonatal BPD rats in vitro by demethylating the P16 gene. PMID- 27663363 TI - Experimental elevation of wildlife testosterone using silastic tube implants. AB - Testosterone (T) is a key androgen that mediates vertebrate molecular, cellular, and behavioral processes. Its manipulation is therefore of interest to a vast number of researchers studying animal behavior and reproduction, among others. Here, the usage of silastic implants across wildlife species is reviewed, and a method to manipulate rock hyrax (Procavia capensis) testosterone levels using silastic implants is presented. Using a series of in-vitro and in-vivo experiments, the secretion patterns of silastic tubes and silastic glue were tested and were surprisingly found to be similar. In addition, we studied endogenous T levels in wild-captured rock hyraxes (Procavia capensis), and using T implants succeeded in elevating T to the maximal physiological concentrations recorded during the mating period. The number of implants that were inserted was the only predictor of T levels, and seven 20mm implants were found to be the optimal dose. Implants induced sexual behaviors in the non-reproductive period. The duration of time that the implants were in the hyrax was the only significant factor that influenced the amount of T left over in the implant once it was removed. All together we affirm that T implants may offer a versatile tool for wildlife behavioral research by elevating T levels in the non-breeding period to maximal breeding levels. PMID- 27663364 TI - Periparturient immunosuppression and strategies to improve dairy cow health during the periparturient period. AB - Common health problems observed during peripartum include milk fever, mastitis, fatty liver disease, ketosis, dystocia, retained placenta, metritis, hypomagnesaemia and abomasal displacements. The increased incidence of health problems observed during the periparturient period can be partly attributed to suboptimal immune responses. Factors contributing to decreased periparturient immunity include the act of parturition itself, impaired leukocytic activity, effects of colostrogenesis and lactogenesis, and associated hypocalcemia and negative energy balance. Nutritional and other management strategies represent a relevant short-term strategy aimed at improving the health and welfare of the transitioning cow. Additionally, it is important to consider improving the health of dairy herds through the genetic selection of animals with enhanced robustness by identifying those with superior disease resistance or resilience in the face of infection. As a consequence these animals are better able to cope with the production and environmental stresses. These may provide long-term selection strategies for improving the health and welfare of the transitioning cow particularly when combined with sound management practices, allowing dairy cattle to reach their full genetic potential. PMID- 27663365 TI - Efficacy of allogeneic mesenchymal stem cell administration in a model of acute ischemic kidney injury in cats. AB - OBJECTIVE: To evaluate the effects of allogeneic mesenchymal stem cells (MSCs) in a model of ischemic acute kidney injury (AKI). STUDY DESIGN: Randomized controlled trial. ANIMALS: Adult, purpose-bred research cats (n=15) and a historical reference group (n=3). METHODS: Cats underwent unilateral, in vivo, warm renal ischemia, then intravenous administration of 4 million adipose-derived MSCs, bone marrow-derived MSCs, or fibroblasts (n=5/treatment) 1h after reperfusion. Serum creatinine and blood urea nitrogen concentrations were measured at baseline and days 1 and 6. Urine specific gravity, urine protein to urine creatinine ratio, and glomerular filtration rate were measured at baseline and day 6. Both kidneys were harvested on day 6; histopathology was described and scored and smooth muscle actin was quantified with histomorphometry. A 2-way ANOVA was used to compare time and treatment. Chi square analysis was used to determine the % of cats with at least International Renal Interest Society (IRIS) Grade 1 AKI. RESULTS: Time, but not treatment, had a significant effect on renal function. No difference was noted in % of cats with IRIS AKI. Significantly fewer mitotic figures were observed in ischemic kidneys that received bone-marrow derived MSCs vs. fibroblasts. No differences in smooth muscle actin staining were noted. CONCLUSIONS: This study did not support the use of allogeneic MSCs in AKI in the regimen described here. Type of renal injury, MSC dose, allogenicity, duration, and route or timing of administration could influence the efficacy MSCs. PMID- 27663366 TI - Investigating the potential role of vitamin E in modulating the immunosuppressive effects of tylvalosin and florfenicol in broiler chickens. AB - Tylvalosin (TVS) is a third-generation macrolide drug used for prophylaxis and treatment of mycoplasma, however; it is supposed to possess an immunosuppressive effect. In the current study, the immunosuppressive effect of TVS and florfenicol (FFC) and the potential immunomodulatory role of Vit E were investigated. The experiment included one day old chick groups treated with either TVS, FFC, Vit E, TVS/Vit E, FFC/Vit E and control non-treated group. Chicks were vaccinated with inactivated H9N2 avian influenza (AI) vaccine and humoral antibody titers to viral antigen as well as innate immunity (serum lysozyme activity and nitric oxide levels) were evaluated. Total and differential leucocytic counts, serum liver enzymes level, blood leucocytic DNA damage and cellular area percentages within the lymphoid organs were also screened. Treatment with TVS and FFC significantly decreased immune response of chickens while treatment with Vit E improved the humoral immune response at 4 and 5weeks post-vaccination. Vit E also significantly increased the cellular immune response. The combination of Vit E with either TVS or FFC modulated their immunosuppressive effect and resulted in mild immunostimulatory effects. TVS alone induced a genotoxic effect on chickens' blood leucocytes and the genotoxicity was inhibited by combination of TVS with Vit E. Histopathology revealed that chickens treated with either TVS or FFC exhibited toxic effect on the lymphatic tissues. PMID- 27663367 TI - Pathogenesis of highly pathogenic porcine reproductive and respiratory syndrome virus in Chinese Tibetan swine. AB - Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) was first characterized in 2006 in China, and it causes great economic losses to the Chinese swine production industry. A China Landrace pig, the Tibetan pig, which has striking phenotypic and physiological differences from lowland pigs, is mainly distributed in the Tibetan highlands of China. The susceptibility of the Tibetan pig to HP-PRRSV has not been reported. In this study, 15 4-week-old Tibetan piglets were divided into three groups, and their susceptibility to HP PRRSV was examined in the highland region. Five pigs in group 1 were inoculated intranasally with HP-PRRSV strain BB0907. At 2days post-inoculation, five other pigs were introduced into this group and then removed to a separated room to serve as contact group 2. Meanwhile, five pigs in group 3 were mock infected and used as controls. The results showed that the pigs in the inoculated and contact groups showed high fevers and clear clinical signs, including depression, anorexia, lethargy, sticky eye secretions, and hind limb paralysis, with high mortality. The main symptom was interstitial pneumonia. Viremia appeared on days 4 to 14 post-infection. HP-PRRSV infection resulted in inflammatory responses within the first week of infection, as evidenced by the expression of tumor necrosis factor alpha, interleukin (IL)-1beta, IL-6, and IL-10. All the data indicate that the Tibetan pig is susceptible to HP-PRRSV infection. Thus, it is necessary to investigate and prevent PRRSV infections in the highland region in China. PMID- 27663368 TI - Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida. AB - The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection. PMID- 27663369 TI - In vitro investigations into the use of antimicrobials in combination to maintain efficacy of fluoroquinolones in poultry. AB - The aim of this study was to determine if apramycin, colistin or lincomycin spectinomycin, in combination with enrofloxacin, was able prevent the emergence of mutants with reduced susceptibility to fluoroquinolone antibiotics in vitro. MICs were determined for enrofloxacin alone and in combination for panels of Campylobacter (n=37), Escherichia coli (n=52) and Salmonella (n=52) isolates. MIC results suggested that apramycin, colistin and lincomycin-spectinomycin worked in an additive/indifferent way when each was combined with enrofloxacin. Apramycin was considered the most promising antibiotic for combination-therapy in conjunction with enrofloxacin, and further evaluations (MBCs, MPCs and time-kill curves) were performed for this combination for selected isolates. Results suggest combination-therapy of enrofloxacin with apramycin increases the efficacy, as well as decreasing the emergence and survival of bacteria with mutational resistance to fluoroquinolone antibiotics. Such combination-therapy, minimising the development of mutational resistance, may have relevance for Campylobacter, E. coli and Salmonella infections in poultry. PMID- 27663370 TI - Circulating strains of variant infectious bursal disease virus may pose a challenge for antibiotic-free chicken farming in Canada. AB - Antibiotic-free and safe animal products are most desirable among consumers. However, ensuring safe poultry products is a challenging task when the chicken immune system is compromised. Infectious bursal disease virus (IBDV) causes immunosuppression and predisposes chickens to secondary infections. Breeder vaccination against IBDV is routinely practiced for producing chicks with maternally-derived antibody (MAb) to prevent infection in newly hatched chicks. The majority of IBDV circulating in Canadian farms are variant strains (vIBDV). Whether circulating vIBDV strains are immunosuppressive in chicks or are amenable to current vaccine regimens has not previously been tested through challenge studies. In this study, one-day-old broiler chicks (n=240) carrying MAb were obtained from broiler breeders vaccinated with commercial IBDV vaccines. In the first set of experiments (n=40/group), at six days post-hatch, one group was challenged with a Canadian field isolate, vIBDV (strain-SK09) (3*10(3) EID50). The second and the third groups (controls) were inoculated with non immunosuppressive IBDV D-78 (10*10(3) TCID50) and saline, respectively. Histopathological examination on days 14 and 30 post-challenge revealed that despite the high level of MAb, vIBDV (SK09) caused severe bursal damage in chicks. Another set of experiments with treatment groups as above, demonstrated that pre-exposure of chicks with vIBDV (SK09) caused immunosuppression resulting in significantly higher mortality and disease severity in chicks challenged with a virulent strain of Escherichia coli (E. coli). Our data provide evidence that IBDV strains circulating in Canada are immunosuppressive, not amenable to current anti-IBDV vaccination strategy, and a potential threat to antibiotic-free chicken farming. PMID- 27663371 TI - Effects of administration of a local anaesthetic and/or an NSAID and of docking length on the behaviour of piglets during 5h after tail docking. AB - In many countries, piglets are tail docked to prevent tail biting. The aim of this study was 1) to evaluate the efficacy of a local anaesthetic and/or NSAID to reduce pain caused by tail docking; and 2) to examine interactions with docking length. This was examined in 295 piglets docked by hot iron cautery 2-4days after birth and based on behaviour during docking as well as the following 5h. The study involved three main factors: local anaesthetic (Lidocain), NSAID (Meloxicam) and docking length. Either 100%, 75%, 50% or 25% of the tails were left on the body of the piglets. Irrespective of the tail length, tail docking led to signs of procedural pain, which could be reduced by administration of Lidocain. Preemptive use of Meloxicam did not affect the signs of procedural pain. The results show that tail docking led to behavioural changes throughout the 5h observation period indicating that effects of this management routine are more persistent than earlier suggested, and suggesting that docking length may influence the post-surgical behaviour of piglets. By use of the present sites of injection and dosages, neither local anaesthetic nor NSAID had marked effects on post-surgical behavioural changes induced by tail docking. Hence, if tail docking is to be performed, more research is needed in order to develop practical methods for on-farm piglet pain relief. PMID- 27663372 TI - Evaluation of qPCR and phase I and II antibodies for detection of Coxiella burnetii infection in cattle. AB - Diagnosis of Q fever in cattle is not easy due to the need to test the samples by both serological and molecular methods. Aim of this study was to evaluate qPCR, and phase I and II antibodies for detection of C. burnetii infection in cattle. A total of 187 bovine blood and vaginal swabs, and 97 milk samples, were tested. Limitations of serological tests were that the available indirect enzyme linked immunosorbent assay (iELISA) could lose positive results if antibody titres were low; or phase II antibodies were present. The highest level of correlation between iELISA and complement fixation test (CFT) was noted with the antigen specific phase I antibodies. Neither the mode of shedding nor its intensity correlated with phase I and II antibodies, but positive results in CFT mixed phase and shedding in vaginal mucous did correlate, and showed the highest correlation. Antigenic diversity, and variability could be crucial in laboratory diagnosis of Q fever. PMID- 27663373 TI - Texture analysis of B-mode ultrasound images to stage hepatic lipidosis in the dairy cow: A methodological study. AB - Hepatic lipidosis is the most diffused hepatic disease in the lactating cow. A new methodology to estimate the degree of fatty infiltration of the liver in lactating cows by means of texture analysis of B-mode ultrasound images is proposed. B-mode ultrasonography of the liver was performed in 48 Holstein Friesian cows using standardized ultrasound parameters. Liver biopsies to determine the triacylglycerol content of the liver (TAGqa) were obtained from each animal. A large number of texture parameters were calculated on the ultrasound images by means of a free software. Based on the TAGqa content of the liver, 29 samples were classified as mild (TAGqa<50mg/g), 6 as moderate (50mg/g100mg/g) and 13 as severe (TAG>100mg/g) in steatosis. Stepwise linear regression analysis was performed to predict the TAGqa content of the liver (TAGpred) from the texture parameters calculated on the ultrasound images. A five-variable model was used to predict the TAG content from the ultrasound images. The regression model explained 83.4% of the variance. An area under the curve (AUC) of 0.949 was calculated for <50mg/g vs >50mg/g of TAGqa; using an optimal cut-off value of 72mg/g TAGpred had a sensitivity of 86.2% and a specificity of 84.2%. An AUC of 0.978 for <100mg/g vs >100mg/g of TAGqa was calculated; using an optimal cut-off value of 89mg/g, TAGpred sensitivity was 92.3% and specificity was 88.6%. Texture analysis of B-mode ultrasound images may therefore be used to accurately predict the TAG content of the liver in lactating cows. PMID- 27663374 TI - Potential probiotics from Indian major carp, Cirrhinus mrigala. Characterization, pathogen inhibitory activity, partial characterization of bacteriocin and production of exoenzymes. AB - The study explored antagonistic activity of the cellular components of potential probiotic bacteria from mrigal (Cirrhinus mrigala) against fish pathogens with a basic insight of the chemical nature of the antagonistic compound. Totally 208 autochthonous gut bacteria were isolated, of which 22 strains revealed antagonism towards >=2 of the six common fish pathogens. Zones of inhibition (halo diameter) were presented as score and the four most promising strains were selected as putative probiotics based on the cumulative score assigned. Further, evaluation of different cellular components exhibited bactericidal activity against the fish pathogens. Verification of other probiotic properties revealed that each of the selected strains produced diverse extra-cellular enzymes. The selected strains grew better in intestinal mucus than skin mucus, were resistant to diluted bile juice (2-20%) and safe for the target fish. The extracellular product used as crude bacteriocin revealed thermostability (up to 90 degrees C) and activity over wide pH range (4-9). Partial loss of activity through treatment with proteinase-K and trypsin indicated proteinaceous nature of the antibacterial compound produced by the probiotic strains. 16S rRNA partial gene sequencing revealed that the four strains CM1FG7, CM1HG5, CM3FG19 and CM3HG10 were similar to Bacillus stratosphericus (KM277362), Bacillus aerophilus (KM277363), Bacillus licheniformis (KM277364) and Solibacillus silvestris (KM277365), respectively. PMID- 27663375 TI - Bovine P-selectin mediates leukocyte adhesion and is highly polymorphic in dairy breeds. AB - Bovine P-selectin (SELP) mediates leukocyte rolling and primes leukocyte adhesion to endothelium, both essential for leukocyte recruitment to an infection site. We investigated SELP-mediated adhesion between bovine peripheral blood leukocytes (PBLs) and cultured bovine aortic endothelial cells pre-activated with lipopolysaccharide (LPS). We examined gene polymorphism for bovine selectins SELP, l-selectin (SELL) and E-selectin (SELE) and compared their SNP frequency between five dairy breeds (Holstein, Friesian, Jersey, Ayrshire and Brown Swiss). LPS treatment caused a rapid (10min) and slower (4h) enhancement of PBL adhesion (P<0.01). Antibody blocking of SELP inhibited LPS induced cell adhesion. SELP was highly polymorphic, with 9 of the 13 SNPs in its exons, whereas only three synonymous SNPs in SELL and one in SELE. The resulting amino acid changes for the three missense SELP SNP were located in the lectin domain and in two consensus repeat (CR) regions, CR2 and CR5. The Val475Met variant locus in the CR4 and CR5 linking region was very close to a predicted N-acetyl-d-glucosamine glycosylation site, which is likely to influence SELP function. The AA genotype was under represented, only being found in 1% of 373 heifers genotyped from the 5 breeds (P=0.056), suggesting that AA homozygous animals carrying the Val475Met substitution for SELP may have compromised development. Our study thus confirmed that SELP mediates the attachment of PBL to endothelium and provides novel evidence that its high polymorphism is likely to affect biological function. This may potentially influence leukocyte migration and fertility, both key to successful performance in dairy cows. PMID- 27663376 TI - Identification and function analysis of the host cell protein that interacted with Orf virus Bcl-2-like protein ORFV125. AB - Orf virus (ORFV) causes contagious ecthyma, a non-systemic skin disease in sheep and goat. Bioinformatics analysis showed that ORFV125 has Bcl-2-like homologous domain and 3D structurally, it is generally known that Bcl-2 protein is known to be a key protein to control cell apoptosis. Maybe ORFV125 act as a Bcl-2-like manner to control cell apoptosis, but its exact function isn't very clear. So in this study, we use yeast two-hybrid system to identity the putative host cell protein interacting partners of ORFV125, and meanwhile using the data obtained from the Gene Ontology, Uniprot, and Kyoto Encyclopedia of Genes and Genomes databases to analysis the functions and pathways associated with them. Finally, five host proteins were shown to be interacted with ORFV125, including cytochrome b (cytb) gene, GUCY2C, BIRC5, GTF3C6 and SERBP1, we also found that BIRC5 has complex biological functions, can inhibit apoptosis, promote cell transformation and are involved in mitosis, and the interaction network of BIRC5 and ORFV125 were constructed. These findings provide a foundation to better understand the biology of the interactions between ORFV125 and the host proteins with which it directly interacts with and resultant downstream events. PMID- 27663378 TI - Significant mucosal sIgA production after a single oral or parenteral administration using in vivo CD40 targeting in the chicken. AB - Many pathogens enter the host through mucosal surfaces and spread rapidly via the circulation. The most effective way to prevent disease is to establish mucosal and systemic immunity against the pathogen. However, current vaccination programs in poultry industry require repeated administrations of live-attenuated virus or large amounts (10 to 100MUg) of antigen together with adjuvant to induce specific secretory IgA immune responses at the mucosal effector sites. In the present study, we show that a single administration of 0.4MUg of oligopeptide complexed with an agonistic anti-chicken CD40 (chCD40) monoclonal antibody (Mab) effectively targets antigen-presenting cells of the bird's mucosa-associated lymphoid tissue in vivo, and induces peptide-specific secretory IgA (sIgA) in the trachea 7days post administration. Anti-chCD40 Mab-peptide complex was administered once to four-week old male Leghorns via various mucosal routes (orally, via cloacal drinking, or oculo-nasally) or via subcutaneous (s.c.) immunization. Immunization through any of the three mucosal induction routes induced significant peptide-specific mucosal sIgA responses 7 and 14days after immunization. Interestingly, s.c. injection of the complex also induced mucosal sIgA. Our data suggest in vivo targeting of CD40 as a potential adjuvant platform, particularly for the purpose of enhancing and speeding up mucosal vaccine responses in chickens, and potentially other food animals. This is the first study able to elicit specific sIgA immune responses in remote mucosal sites with a single administration of only 0.4MUg of antigen. PMID- 27663377 TI - Expression and localization of fibroblast growth factor (FGF) family in buffalo ovarian follicle during different stages of development and modulatory role of FGF2 on steroidogenesis and survival of cultured buffalo granulosa cells. AB - The present study investigated the expression and localization of FGF and its functional receptors in the follicle of buffalo and the treatment of FGF2 on mRNA expression of CYP19A1 (aromatase), PCNA, and BAX (BCL-2 associated X protein) in cultured buffalo granulosa cells (GCs). Follicles were classified into four groups based on size and E2 level in follicular fluid (FF): F1, 4-6mm diameter, E2<0.5ng/ml of FF; F2, 7-9mm, E2=0.5-5ng/ml; F3, 10-13mm, E2=5-40ng/ml; F4, >14mm, E2>180ng/ml. The qPCR studies revealed that the mRNA expression of FGF1, FGF2 and FGF7 were maximum (P<0.05) in theca interna (TI) whereas the transcripts of FGFR1, FGFR2, FGFR2IIIB and FGFR2IIIC were up-regulated (P<0.05) in GCs of F4 follicles. Protein expression of most members were maximum (P<0.05) in F4 follicles except FGFR3 and FGFR4. All members were localized in GC and TI with a stage specific immunoreactivity. Primary culture of GCs with treatment of FGF2 at different dose-time combinations revealed that the mRNA expression and immunoreactivity of CYP19A1 and PCNA were maximum (P<0.05) whereas BAX was minimum (P<0.05) with 200ng/ml at 72h of incubation. The findings indicate that FGF family members are expressed in a regulated manner in buffalo ovarian follicles during different stages of development where FGF2 may promote steroidogenesis and GC survival through autocrine and paracrine manner. PMID- 27663379 TI - Association between vitamin D supplementation and severity of tuberculosis in wild boar and red deer. AB - Tuberculosis (TB) is a chronic disease affecting humans and other mammal species. Severity of TB caused by Mycobacterium tuberculosis in humans seems to be influenced by nutritional factors like vitamin D3 intake. However, this relationship has been scarcely studied in cattle and other mammals infected with Mycobacterium bovis. The aim of this work was to assess if wildlife reservoirs of M. bovis show different levels of TB severity depending on the level of vitamin D found in serum after supplementation with vitamin D3. Forty hunted wildlife mammals were included in this study: 20 wild boar and 20 red deer. Ten wild boar and ten red deer had been supplemented with a vitamin D3-enriched food, whereas the remaining animals had received no supplementation. TB diagnosis was carried out in each animal based on microbiological isolation of M. bovis. Animals infected with M. bovis were then classified as animals with localized or generalized TB depending on the location and dissemination of the lesions. Furthermore, serum levels of vitamin D2 and D3 were determined in each animal to evaluate differences not only between supplemented and non-supplemented animals but also between those with localized and generalized TB. Levels of vitamin D3 found in both, supplemented wild boar and red deer, were significantly higher than those found in the non-supplemented animals. Interestingly, higher levels of vitamin D3 were observed in animals suffering localized TB when compared to animals with generalized TB suggesting that vitamin D3 concentration correlates negatively with TB severity in these wildlife reservoirs. PMID- 27663380 TI - Seroprevalence of respiratory viral pathogens of indigenous calves in Western Kenya. AB - Most studies of infectious diseases in East African cattle have concentrated on gastro-intestinal parasites and vector-borne diseases. As a result, relatively little is known about viral diseases, except for those that are clinically symptomatic or which affect international trade such as foot and mouth disease, bluetongue and epizootic haemorrhagic disease. Here, we investigate the seroprevalence, distribution and relationship between the viruses involved in respiratory disease, infectious bovine rhinotracheitis virus (IBR), bovine parainfluenza virus Type 3 (PIV3) and bovine viral diarrhoea virus (BVDV) in East African Shorthorn Zebu calves. These viruses contribute to the bovine respiratory disease complex (BRD) which is responsible for major economic losses in cattle from intensive farming systems as a result of pneumonia. We found that calves experience similar risks of infection for IBR, PIV3, and BVDV with a seroprevalence of 20.9%, 20.1% and 19.8% respectively. We confirm that positive associations exist between IBR, PIV3 and BVDV; being seropositive for any one of these three viruses means that an individual is more likely to be seropositive for the other two viruses than expected by chance. PMID- 27663381 TI - Isolation, characterization and evaluation of probiotic lactic acid bacteria for potential use in animal production. AB - In livestock production, lactic acid bacteria (LAB) are the most common microorganisms used as probiotics. For such use, these bacteria must be correctly identified and characterized to ensure their safety and efficiency. In the present study, LAB were isolated from broiler excreta, where a fermentation process was used. Nine among sixteen isolates were identified by biochemical and molecular (sequencing of the 16S rRNA gene) methods as Lactobacillus crispatus (n=1), Lactobacillus pentosus (n=1), Weissella cibaria (n=1), Pediococcus pentosaceus (n=2) and Enterococcus hirae (n=4). Subsequently, these bacteria were characterized for their growth capabilities, lactic acid production, acidic pH and bile salts tolerance, cell surface hydrophobicity, antimicrobial susceptibility and antagonistic activity. Lactobacillus pentosus strain LB-31, which showed the best characteristics, was selected for further analysis. This strain was administered to broilers and showed the ability of modulating the immune response and producing beneficial effects on morpho-physiological, productive and health indicators of the animals. PMID- 27663382 TI - Variability in Flow-Imaging Microscopy Measurements and Considerations for Biopharmaceutical Development. AB - Flow-imaging microscopy is widely used in the biopharmaceutical industry to characterize populations of subvisible (1-100 MUm) particles due to high sensitivity and the ability to discriminate different particle morphologies. The present work provides a comprehensive assessment of the capabilities of flow imaging microscopy by exploring the impacts of a variety of factors on the observed variability of these measurements. A novel graphical presentation is proposed to facilitate both determination of expected levels and detection of potential atypical results. Data collected across different products and container-closure systems illustrate that a substantial amount of historical experience is typically required to adequately define the expected levels of subvisible particles for any specific system. It is also shown, however, that an appropriate level of control can be demonstrated without the need to pool large numbers of containers or perform replicate measurements. PMID- 27663383 TI - A Comprehensive Evaluation of Nanoparticle Tracking Analysis (NanoSight) for Characterization of Proteinaceous Submicron Particles. AB - Nanoparticle tracking analysis (NTA) has attracted great interest for application in the field of submicron particle characterization for biopharmaceuticals. It has the virtue of direct sample visualization and particle-by-particle tracking, but the complexity of method development has limited its routine applicability. We systematically evaluated data collection and processing parameters as well as sample handling methods using shake-stressed protein samples. The camera shutter and gain were identified as the key factors influencing NTA results. We also demonstrated that sample filtration was necessary for NTA analysis if there were high numbers of micron particles, whereas the choice of filter membrane was critical for data quality. Sample dilution into corresponding formulation buffer did not affect particle size distributions in our study. Finally, NTA analysis exhibited excellent repeatability in intraday comparison of multiple measurements on the same sample and interday comparison on different batches of samples. Shaking-induced protein aggregation could also be sensitively monitored by NTA. In conclusion, NTA analysis can be used as a robust stability-indicating method for the characterization of proteinaceous submicron particles and thereby complement other analytical methods, provided that consistent sample handling and parametric settings are established for the specific case study. PMID- 27663384 TI - In Vitro Release Mechanisms of Doxorubicin From a Clinical Bead Drug-Delivery System. AB - The release rate of doxorubicin (DOX) from the drug-delivery system (DDS), DC Bead, was studied by 2 miniaturized in vitro methods: free-flowing and sample reservoir. The dependencies of the release mechanisms on in vitro system conditions were investigated experimentally and by theoretical modeling. An inverse relationship was found between release rates and bead size, most likely due to the greater total surface area. The release rates correlated positively with temperature, release medium volume, and buffer strength, although the release medium volume had larger effect than the buffer strength. The sample reservoir method generated slower release rates, which described the in vivo release profile more accurately than the free-flowing method. There was no difference between a pH of 6.3 or 7.4 on the release rate, implying that the slightly acidic tumor microenvironment is less importance for drug release. A positive correlation between stirring rate and release rate for all DDS sizes was observed, which suggests film controlled release. Theoretical modeling highlighted the influence of local equilibrium of protonation, self-aggregation, and bead material interactions of DOX. The theoretical release model might describe the observed larger sensitivity of the release rate to the volume of the release medium compared to buffer strength. A combination of miniaturized in vitro methods and theoretical modeling are useful to identify the important parameters and processes for DOX release from a micro gel-based DDS. PMID- 27663385 TI - [Facial linear scleroderma associated with neurological abnormalities relating to microangiopathy]. AB - BACKGROUND: Linear scleroderma is a fibrotic disease affecting the skin and sometimes the deeper tissues. We describe a case of scleroderma associated with neurological anomalies not previously reported in the literature. PATIENTS AND METHODS: A 16-year-old male patient presented in 2009 for hemifacial linear scleroderma. Treatment with methotrexate for 14 months resulted in stabilization of the disease. In 2013, we noted worsening of the patient's skin lesions as well as homolateral ptosis. Head MRI revealed unilateral hemispherical signal abnormalities with T2 hypersignal in the basal gangliaand punctate foci of T2* hyposignal corresponding to microbleeds. In 2014 and 2015, the patient presented three brief episodes of right hemicorpus paresthesia (with temporary aphasia followed by headache during the first episode). The head MRI showed worsening of the anomalies, suggesting progressing cerebral microangiopathy. DISCUSSION: Clinicians may not always be familiar with the neurological abnormalities associated with localized facial scleroderma even if such abnormalities are not uncommon (their exact prevalence is unknown). Clinical signs vary but, in most cases, the radiological features are calcifications and hyperintense foci of white matter lesions in T2. As far as we are aware, there have been no reports to date of microbleeding as observed in our patient. The worsening with time of these neurological anomalies of unknown origin does not appear to be correlated with the dermatological lesions. It is important for dermatologists be aware of these complications of facial linear scleroderma. PMID- 27663386 TI - Eligibility of real-life patients with COPD for inclusion in trials of inhaled long-acting bronchodilator therapy. AB - BACKGROUND: Management guidelines of chronic obstructive pulmonary disease (COPD) are mainly based on results of randomised controlled trials (RCTs), but some authors have suggested limited representativeness of patients included in these trials. No previous studies have applied the full range of selection criteria to a broad COPD patient population in a real-life setting. METHODS: We identified all RCTs of inhaled long-acting bronchodilator therapy, during 1999-2013, at ClinicalTrials.gov and translated trial selection criteria into definitions compatible with electronic medical records. Eligibility was calculated for each RCT by applying these criteria to a uniquely representative, well-characterised population of patients with COPD from the Optimum Patient Care Research Database (OPCRD). RESULTS: Median eligibility of 36 893 patients with COPD for participation in 31 RCTs was 23 % (interquartile range 12-38). Two studies of olodaterol showed the highest eligibility of 55 and 58 %. Conversely, the lowest eligibility was observed in two studies that required a history of exacerbations in the past year (3.5 and 3.9 %). For the patient subgroup with modified Medical Research Council score >=2, the overall median eligibility was 27 %. CONCLUSIONS: By applying an extensive range of RCT selection criteria to a large, representative COPD patient population, this study highlights that the interpretation of results from RCTs must take into account that RCT participants are variably, but generally more representative of patients in the community than previously believed. PMID- 27663389 TI - Immunovirotherapy with measles virus strains in combination with anti-PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment. AB - Background: Glioblastoma (GBM) is the most common primary malignant brain tumor and has a dismal prognosis. Measles virus (MV) therapy of GBM is a promising strategy due to preclinical efficacy, excellent clinical safety, and its ability to evoke antitumor pro-inflammatory responses. We hypothesized that combining anti- programmed cell death protein 1 (anti-PD-1) blockade and MV therapy can overcome immunosuppression and enhance immune effector cell responses against GBM, thus improving therapeutic outcome. Methods: In vitro assays of MV infection of glioma cells and infected glioma cells with mouse microglia +/- aPD-1 blockade were established to assess damage associated molecular pattern (DAMP) molecule production, migration, and pro-inflammatory effects. C57BL/6 or athymic mice bearing syngeneic orthotopic GL261 gliomas were treated with MV, aPD-1, and combination treatment. T2* weighted immune cell-specific MRI and fluorescence activated cell sorting (FACS) analysis of treated mouse brains was used to examine adaptive immune responses following therapy. Results: In vitro, MV infection induced human GBM cell secretion of DAMP (high-mobility group protein 1, heat shock protein 90) and upregulated programmed cell death ligand 1 (PD-L1). MV infection of GL261 murine glioma cells resulted in a pro-inflammatory response and increased migration of BV2 microglia. In vivo, MV+aPD-1 therapy synergistically enhanced survival of C57BL/6 mice bearing syngeneic orthotopic GL261 gliomas. MRI showed increased inflammatory cell influx into the brains of mice treated with MV+aPD-1; FACS analysis confirmed increased T-cell influx predominantly consisting of activated CD8+ T cells. Conclusions: This report demonstrates that oncolytic measles virotherapy in combination with aPD-1 blockade significantly improves survival outcome in a syngeneic GBM model and supports the potential of clinical/translational strategies combining MV with alphaPD-1 therapy in GBM treatment. PMID- 27663391 TI - Pharmacists' barriers and facilitators on implementing a post-discharge home visit. AB - BACKGROUND: Introducing a post-discharge community pharmacist home visit can secure continuity of care and prevent drug-related problems. Currently, this type of pharmaceutical care is not standard practice and implementation is challenging. Mapping the factors influencing the implementation of this new form of care is crucial to ensure successful embedding. OBJECTIVE: To explore which barriers and facilitators influence community pharmacists' adoption of a post discharge home visit. METHODS: A mixed methods study was conducted with community pharmacists who had recently participated in a study that evaluated the effectiveness of a post-discharge home visit in identifying drug-related problems. Four focus groups were held guided by a topic guide based on the framework of Greenhalgh et al. After the focus groups, major barriers and facilitators were formulated into statements and presented to all participants in a scoring list to rank for relevance and feasibility in daily practice. RESULTS: Twenty-two of the eligible 26 pharmacists participated in the focus groups. Twenty pharmacists (91%) returned the scoring list containing 21 statements. Most of these statements were perceived as both relevant and feasible by the responding pharmacists. A small number scored high on relevance but low on feasibility, making these potential important barriers to overcome for broad implementation. These were the necessity of dedicated time for performing pharmaceutical care, implementing the home visit in pharmacists' daily routine and an adequate reimbursement fee for the home visit. CONCLUSIONS: The key to successful implementation of a post-discharge home visit may lay in two facilitators which are partly interrelated: changing daily routine and reimbursement. Reimbursement will be a strong incentive, but additional efforts will be needed to reprioritize daily routines. PMID- 27663390 TI - Feasibility, phase I, and phase II studies of tandutinib, an oral platelet derived growth factor receptor-beta tyrosine kinase inhibitor, in patients with recurrent glioblastoma. AB - Background: Platelet-derived growth factor (PDGF) signaling is important in gliomagenesis and PDGF receptor-beta is expressed on most endothelial cells in glioblastoma specimens. Methods: We report the results of feasibility, phase I, and phase II studies of tandutinib (MLN518), an orally bioavailable inhibitor of type III receptor tyrosine kinases including PDGF receptor-beta, Fms-like tyrosine kinase 3, and c-Kit in patients with recurrent glioblastoma. Results: In an initial feasibility study, 6 patients underwent resection for recurrent glioblastoma after receiving tandutinib 500mg twice daily for 7 days. The mean ratio of tandutinib concentration in brain tumor-to-plasma was 13.1+/-8.9 in 4 of the 6 patients. In the phase I study, 19 patients were treated at 500, 600, and 700mg twice daily dose levels. The maximum tolerated dose was found to be 600mg twice daily, and 30 patients were treated with this dose in the phase II study. The trial was closed after interim analysis, as the prespecified goal of patients alive and progression-free survival at 6 months was not achieved. Biomarker studies suggested that tandutinib treatment could lead to vascular disruption rather than normalization, which was associated with rapid progression. Conclusions: Tandutinib readily distributed into the brain following oral administration and achieved concentrations within the tumor that exceed the corresponding concentration in plasma. The phase II study was closed at interim analysis due to lack of efficacy, although this study was not enriched for glioblastomas with alterations of the PDGF pathway. PMID- 27663388 TI - Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival. AB - Background: Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. Methods: In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. Results: The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (>=100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). Conclusions: The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification. PMID- 27663392 TI - Community-dwelling older people's attitudes towards deprescribing in Canada. AB - BACKGROUND: While there is evidence that supervised withdrawal of inappropriate medications might be beneficial for individuals with polypharmacy, little is known about their attitudes towards deprescribing. OBJECTIVE: This study aimed to describe the situation among older community-dwelling Canadians. METHODS: A self administered survey was adapted from the Patients' Attitudes Towards Deprescribing questionnaire and distributed to 10 community pharmacies and 2 community centers. The participants rated their agreement on statements about polypharmacy/deprescribing on a 5-point, Likert-type scale. Correlations between the desire to have medications deprescribed and survey items were evaluated using Spearman's Rho and Goodman and Kurska's gamma rank correlations. RESULTS: From the 129 participants, 63% were women [median age: 76 (IQR:71-80); median number medication: 6 (IQR: 3-8)]. A proportion of 50.8% (95%CI: 41.6%-60.0%) expressed the desire to reduce their number of medications. This desire was strongly correlated with the individuals' feeling of taking a large number of medications and moderately correlated with the belief that some of the medications were no longer needed or that they were experiencing side effects. CONCLUSIONS: The results show that older individuals in the community are eager to undertake deprescribing, especially if they have a large number of medications, are experiencing side effects or feel some medications are no longer necessary. PMID- 27663393 TI - Prostate-specific antigen vs. magnetic resonance imaging parameters for assessing oncological outcomes after high intensity-focused ultrasound focal therapy for localized prostate cancer. AB - INTRODUCTION: Focal therapy for localized prostate cancer has the potential for oncological control without the side effects of radical therapies. However, there is currently no validated method for monitoring treatment success. We assessed the diagnostic performance of prostate-specific antigen (PSA) parameters and MRI compared to histological outcomes following focal therapy. PATIENTS AND METHODS: Patients from 3 Ethics Review Board approved prospective studies of focal high intensity-focused ultrasound (HIFU) (Sonablate 500) for localized prostate cancer (T1c-T3a, Gleason grade<=4+3, and PSA<=20). Post-HIFU PSA nadir, 6-month PSA, PSA density, and early (<3wk) and late (6mo) MRI (T2-weighted, dynamic contrast enhanced+/-diffusion-weighted) was assessed for predictive accuracy of cancer on postoperative biopsy, using receiver operating characteristic (ROC) analysis and sensitivity, specificity, and positive and negative predictive estimates. ROC areas for MRI and PSA were compared. Calculations for statistical significance (P<=0.05) were obtained in a subset of patients comparing area under ROC for 6 month MRI and PSA criteria, across 4 different histological definitions of disease significance. RESULTS: Of 118 men, 111 underwent at least 1 postoperative biopsy (median 6 cores), with an overall positive biopsy rate of 37% (41/118), over a mean follow-up period of 716 days post-HIFU. Areas under ROC for early and late MRI were (depending on definition of significant disease) 0.65 to 0.76 and 0.77 to 0.85, respectively, with sensitivity, specificity, and negative predictive values of 68% to 91%, 52% to 55%, and 85% to 98% (early MRI), and 63% to 80%, 67% to 73%, and 86% to 97% (late MRI). The area under the ROC curve was statistically significantly higher for late MRI than 6 months and nadir PSA for residual disease >3mm or any Gleason 4 tumor. CONCLUSIONS: Early and late MRI performed better than PSA measurements in the detection of residual tumor after focal therapy. PMID- 27663394 TI - Modulating Immunosuppression in the Intrapleural Space of Malignant Pleural Mesothelioma and Predictive Biomarkers to Guide Treatment Decisions. PMID- 27663395 TI - Whole Brain Radiotherapy for Patients with Non-Small Cell Lung Cancer with EGFR Mutations-Why and When? PMID- 27663396 TI - Are Liquid Biopsies Ready for Prime Time of Clinical Applications? PMID- 27663397 TI - Exosomal Proteins in Lung Cancer: The Last Frontier in Liquid Biopsies. PMID- 27663399 TI - Erratum. PMID- 27663398 TI - Comment on the Proposals for the Revision of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. PMID- 27663400 TI - Response of Malignant Thymoma to Sorafenib. PMID- 27663401 TI - A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK. PMID- 27663402 TI - Prognostic and Predictive Value of KRAS Mutation in NSCLC. PMID- 27663403 TI - Response to Yamamoto et al. PMID- 27663404 TI - Extensive Acquired Telangiectasias: Comparison of Generalized Essential Telangiectasia and Cutaneous Collagenous Vasculopathy. AB - The late development of symmetrical, ascending telangiectasias over an extensive area of the skin with no associated systemic manifestations is a common presentation of generalized essential telangiectasia (GET). It was recently suggested that cutaneous collagenous vasculopathy (CCV) is clinically identical to GET but that the 2 conditions can be distinguished by their distinctive histopathologic findings. We present 2 patients, both women, with multiple telangiectasias and describe the histopathologic findings that led to the diagnoses of GET and CCV. Dermoscopic findings in both cases were similar, except that the older telangiectasias in the patient with CCV were violaceous and distributed in a tortuous, serpentine pattern. During follow-up 12 years for the woman with GET and 42 years for the woman with CCV we saw that in GET the lesions remained stable in appearance whereas in CCV there was progressive darkening and morphological changes eventually resulting in superficial varicose veins. PMID- 27663405 TI - Relapse of morphea during Nivolumab therapy for lung adenocarcinoma. PMID- 27663406 TI - The impacts of decentralisation on health-related equity: A systematic review of the evidence. AB - BACKGROUND: Decentralised governance of health care has been widely adopted globally over the past three decades. But despite being implemented as a management strategy across many health systems, its impact on health equity is yet unclear. OBJECTIVE: To conduct a systematic literature review of the implications of decentralised governance of health care on equity in health, health care and health financing. METHODS: A systematic search of CINAHL, EconLit, Embase, MEDLINE, PsycINFO, PubMed, Scopus, and Cochrane database of systematic reviews was conducted. Articles that met the inclusion criteria examined entire health systems and the relationship between implementing decentralised governance and health-related equity. The quality of reporting of the included studies was assessed using a 10-point quality rating tool. RESULTS: Out of 808 articles identified, 9 met the inclusion criteria. The included studies were mostly explorative and used a range of quantitative techniques to analyse the relationship between variables of interest. The review found that depending on context, decentralisation could either lead to equity gains or exacerbate inequities. The impact of decentralisation on inequities in health and health care depends on pre-existing socio-economic disparities and financial barriers to access. While decentralisation can lead to inequities in health financing between sub-national jurisdictions, this is minimised with substantial central government transfers and cross subsidisation. CONCLUSION: The implications of decentralised governance of health systems on health-related equity are varied and depend on pre-existing socio-economic and organisational context, the form of decentralisation implemented and the complementary mechanisms implemented alongside decentralisation. PMID- 27663407 TI - Arabidopsis Responds to Alternaria alternata Volatiles by Triggering Plastid Phosphoglucose Isomerase-Independent Mechanisms. AB - Volatile compounds (VCs) emitted by phylogenetically diverse microorganisms (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote photosynthesis, growth, and the accumulation of high levels of starch in leaves through cytokinin (CK)-regulated processes. In Arabidopsis (Arabidopsis thaliana) plants not exposed to VCs, plastidic phosphoglucose isomerase (pPGI) acts as an important determinant of photosynthesis and growth, likely as a consequence of its involvement in the synthesis of plastidic CKs in roots. Moreover, this enzyme plays an important role in connecting the Calvin-Benson cycle with the starch biosynthetic pathway in leaves. To elucidate the mechanisms involved in the responses of plants to microbial VCs and to investigate the extent of pPGI involvement, we characterized pPGI-null pgi1-2 Arabidopsis plants cultured in the presence or absence of VCs emitted by Alternaria alternata We found that volatile emissions from this fungal phytopathogen promote growth, photosynthesis, and the accumulation of plastidic CKs in pgi1-2 leaves. Notably, the mesophyll cells of pgi1-2 leaves accumulated exceptionally high levels of starch following VC exposure. Proteomic analyses revealed that VCs promote global changes in the expression of proteins involved in photosynthesis, starch metabolism, and growth that can account for the observed responses in pgi1-2 plants. The overall data show that Arabidopsis plants can respond to VCs emitted by phytopathogenic microorganisms by triggering pPGI-independent mechanisms. PMID- 27663408 TI - Comparative Analysis of Light-Harvesting Antennae and State Transition in chlorina and cpSRP Mutants. AB - State transitions in photosynthesis provide for the dynamic allocation of a mobile fraction of light-harvesting complex II (LHCII) to photosystem II (PSII) in state I and to photosystem I (PSI) in state II. In the state I-to-state II transition, LHCII is phosphorylated by STN7 and associates with PSI to favor absorption cross-section of PSI. Here, we used Arabidopsis (Arabidopsis thaliana) mutants with defects in chlorophyll (Chl) b biosynthesis or in the chloroplast signal recognition particle (cpSRP) machinery to study the flexible formation of PS-LHC supercomplexes. Intriguingly, we found that impaired Chl b biosynthesis in chlorina1-2 (ch1-2) led to preferentially stabilized LHCI rather than LHCII, while the contents of both LHCI and LHCII were equally depressed in the cpSRP43 deficient mutant (chaos). In view of recent findings on the modified state transitions in LHCI-deficient mutants (Benson et al., 2015), the ch1-2 and chaos mutants were used to assess the influence of varying LHCI/LHCII antenna size on state transitions. Under state II conditions, LHCII-PSI supercomplexes were not formed in both ch1-2 and chaos plants. LHCII phosphorylation was drastically reduced in ch1-2, and the inactivation of STN7 correlates with the lack of state transitions. In contrast, phosphorylated LHCII in chaos was observed to be exclusively associated with PSII complexes, indicating a lack of mobile LHCII in chaos Thus, the comparative analysis of ch1-2 and chaos mutants provides new evidence for the flexible organization of LHCs and enhances our understanding of the reversible allocation of LHCII to the two photosystems. PMID- 27663409 TI - A NAC Transcription Factor Represses Putrescine Biosynthesis and Affects Drought Tolerance. AB - Arginine decarboxylase (ADC)-mediated putrescine biosynthesis plays an important role in plant stress responses, but the transcriptional regulation of ADC in response to abiotic stress is not well understood. We isolated a NAM, ATAF1/2, and CUC (NAC) domain-containing transcription factor, PtrNAC72, from trifoliate orange (Poncirus trifoliata) by yeast one-hybrid screening. PtrNAC72, localized to the nucleus, binds specifically to the promoter of PtADC and acts as a transcriptional repressor. PtrNAC72 expression was induced by cold, drought, and abscisic acid. ADC messenger RNA abundance and putrescine levels were decreased in transgenic tobacco (Nicotiana nudicaulis) plants overexpressing PtrNAC72 but increased, compared with the wild type, in an Arabidopsis (Arabidopsis thaliana) transfer DNA insertion mutant, nac72 While transgenic tobacco lines overexpressing PtrNAC72 were more sensitive to drought, plants of the Arabidopsis nac72 mutant exhibited enhanced drought tolerance, consistent with the accumulation of reactive oxygen species in the tested genotypes. In addition, exogenous application of putrescine to the overexpression lines restored drought tolerance, while treatment with d-arginine, an ADC inhibitor, compromised the drought tolerance of nac72 Taken together, these results demonstrate that PtrNAC72 is a repressor of putrescine biosynthesis and may negatively regulate the drought stress response, at least in part, via the modulation of putrescine associated reactive oxygen species homeostasis. PMID- 27663410 TI - phenoSeeder - A Robot System for Automated Handling and Phenotyping of Individual Seeds. AB - The enormous diversity of seed traits is an intriguing feature and critical for the overwhelming success of higher plants. In particular, seed mass is generally regarded to be key for seedling development but is mostly approximated by using scanning methods delivering only two-dimensional data, often termed seed size. However, three-dimensional traits, such as the volume or mass of single seeds, are very rarely determined in routine measurements. Here, we introduce a device named phenoSeeder, which enables the handling and phenotyping of individual seeds of very different sizes. The system consists of a pick-and-place robot and a modular setup of sensors that can be versatilely extended. Basic biometric traits detected for individual seeds are two-dimensional data from projections, three dimensional data from volumetric measures, and mass, from which seed density is also calculated. Each seed is tracked by an identifier and, after phenotyping, can be planted, sorted, or individually stored for further evaluation or processing (e.g. in routine seed-to-plant tracking pipelines). By investigating seeds of Arabidopsis (Arabidopsis thaliana), rapeseed (Brassica napus), and barley (Hordeum vulgare), we observed that, even for apparently round-shaped seeds of rapeseed, correlations between the projected area and the mass of seeds were much weaker than between volume and mass. This indicates that simple projections may not deliver good proxies for seed mass. Although throughput is limited, we expect that automated seed phenotyping on a single-seed basis can contribute valuable information for applications in a wide range of wild or crop species, including seed classification, seed sorting, and assessment of seed quality. PMID- 27663412 TI - Challenges and Outcomes of Posterior Wall Isolation for Ablation of Atrial Fibrillation. AB - BACKGROUND: The left atrial posterior wall (PW) often contains sites required for maintenance of atrial fibrillation (AF). Electrical isolation of the PW is an important feature of all open surgeries for AF. This study assessed the ability of current ablation techniques to achieve PW isolation (PWI) and its effect on recurrent AF. METHODS AND RESULTS: Fifty-seven consecutive patients with persistent or high-burden paroxysmal AF underwent catheter ablation, which was performed using an endocardial-only (30) or a hybrid endocardial-epicardial procedure (27). The catheter ablation lesion set included pulmonary vein antral isolation and a box lesion on the PW (roof and posterior lines). Success in creating the box lesion was assessed as electrical silence of the PW (voltage <0.1 mV) and exit block in the PW with electrical capture. Cox proportional hazards models were used for analysis of AF recurrence. PWI was achieved in 21 patients (36.8%), more often in patients undergoing hybrid ablation than endocardial ablation alone (51.9% versus 23.3%, P=0.05). Twelve patients underwent redo ablation. Five of 12 had a successful procedural PWI, but all had PW reconnection at the redo procedure. Over a median follow-up of 302 days, 56.1% of the patients were free of atrial arrhythmias. No parameter including procedural PWI was a statistically significant predictor of recurrent atrial arrhythmias. CONCLUSIONS: PWI during catheter ablation for AF is difficult to achieve, especially with endocardial ablation alone. Procedural achievement of PWI in this group of patients was not associated with a reduction in recurrent atrial arrhythmias, but reconnection of the PW was common. PMID- 27663413 TI - Ventricular-Arterial Function and Coupling in the Adult Fontan Circulation. AB - BACKGROUND: In adult Fontan patients, ventricular or arterial dysfunction may impact homeostasis of the Fontan circulation and predispose to heart failure. We sought to characterize ventricular-arterial (VA) properties in adult Fontan patients. METHODS AND RESULTS: Adult Fontan patients (n=170), including those with right (SRV, n=57) and left (SLV, n=113) dominant ventricular morphology, were compared to age, sex, and body size matched controls (n=170). Arterial function, load-insensitive measures of contractility, VA coupling, diastolic function, and ventricular efficiency were assessed. Compared to controls, Fontan patients had similar arterial (Ea), but lower end-systolic ventricular (Ees), elastance, preload recruitable stroke work and peak power index, impaired VA coupling, eccentric remodeling, reduced ventricular efficiency and increased diastolic stiffness (P<0.05 for all). Ventricular efficiency declined steeply with higher heart rate in Fontan, but not control, patients. Among Fontan patients (n=123) and controls (n=162) with preserved cardiac index (CI; >=2.5 L/min per m2), Fontan patients had worse contractility than controls, but CI was preserved owing to relative tachycardia, lower afterload, and eccentric remodeling. However, 25% of Fontan patients had reduced CI and were distinguished from those with preserved CI by less-eccentric remodeling and worse diastolic function, rather than more-impaired contractility. CONCLUSIONS: Adult Fontan patients have contractile and diastolic dysfunction with normal afterload, impaired VA coupling, and reduced ventricular efficiency with heightened sensitivity to heart rate. Maintenance of CI is dependent on lower afterload, eccentric remodeling, and relative preservation of diastolic function. These data contribute to our understanding of circulatory physiology in adult Fontan patients. PMID- 27663414 TI - Factors Associated With Initial Prasugrel Versus Clopidogrel Selection for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From the Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study. AB - BACKGROUND: Few studies have examined how antiplatelet therapies are selected during the routine care of acute myocardial infarction patients, particularly relative to the patient's estimated mortality and bleeding risks. METHODS AND RESULTS: We examined patients presenting with acute myocardial infarction treated with percutaneous coronary intervention at 233 US hospitals in the TRANSLATE-ACS observational study from April 2010 to October 2012. We developed a multivariable logistic regression model to identify factors associated with prasugrel selection. Prasugrel use rates and associated 1-year risk-adjusted major adverse cardiovascular events and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) moderate/severe bleeding outcomes were also examined in relation to predicted mortality and bleeding using the validated Acute Coronary Treatment and Intervention Outcomes (ACTION) risk prediction scores. Among 11 969 patients, 3123 (26%) received prasugrel at the time of percutaneous coronary intervention. The strongest factors associated with prasugrel use included cardiogenic shock (odds ratio [OR] 1.68, 95% CI 1.25 2.26), drug-eluting stent use (OR 1.45, 95% CI 1.31-1.62), and ST-segment elevation myocardial infarction presentation (OR 1.23, 95% CI 1.12-1.35). Older age (OR 0.57, 95% CI 0.0.53-0.61), dialysis (OR 0.56, 95% CI 0.32-0.96), prior history of stroke/transient ischemic attack (OR 0.52, 95% CI 0.38-0.73), and interhospital transfer (OR 0.50, 95% CI 0.46-0.55) were associated with lowest prasugrel selection. Prasugrel was used less often than clopidogrel in patients at higher predicted bleeding risk (21.9% versus 29.7%, P<0.001). Yet paradoxically, prasugrel was also less likely than clopidogrel to be used in patients with higher predicted mortality risk (21.1% versus 30.2%, P<0.001). Adjusted bleeding and outcomes events were similar among those receiving prasugrel and clopidogrel in the 4 subgroups of patients based on bleeding risk and ischemic benefits. CONCLUSIONS: In community practice, prasugrel use may be driven more by bleeding risk rather than ischemic benefit. This may result in underutilization of higher potency ADP receptor inhibitor among patients more likely to derive ischemic benefit. PMID- 27663411 TI - A Rice Ca2+ Binding Protein Is Required for Tapetum Function and Pollen Formation. AB - In flowering plants, successful male reproduction requires the sophisticated interaction between somatic anther wall layers and reproductive cells. Timely degradation of the innermost tissue of the anther wall layer, the tapetal layer, is critical for pollen development. Ca2+ is a well-known stimulus for plant development, but whether it plays a role in affecting male reproduction remains elusive. Here we report a role of Defective in Exine Formation 1 (OsDEX1) in rice (Oryza sativa), a Ca2+ binding protein, in regulating rice tapetal cell degradation and pollen formation. In osdex1 anthers, tapetal cell degeneration is delayed and degradation of the callose wall surrounding the microspores is compromised, leading to aborted pollen formation and complete male sterility. OsDEX1 is expressed in tapetal cells and microspores during early anther development. Recombinant OsDEX1 is able to bind Ca2+ and regulate Ca2+ homeostasis in vitro, and osdex1 exhibited disturbed Ca2+ homeostasis in tapetal cells. Phylogenetic analysis suggested that OsDEX1 may have a conserved function in binding Ca2+ in flowering plants, and genetic complementation of pollen wall defects of an Arabidopsis (Arabidopsis thaliana) dex1 mutant confirmed its evolutionary conservation in pollen development. Collectively, these findings suggest that OsDEX1 plays a fundamental role in the development of tapetal cells and pollen formation, possibly via modulating the Ca2+ homeostasis during pollen development. PMID- 27663416 TI - Newer P2Y12 Inhibitors: How Does the Interventional Cardiologist Choose? PMID- 27663415 TI - Effectiveness of N-Acetylcysteine for the Prevention of Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Conflicting results have been obtained in trials that have evaluated the prophylactic efficacy of N-acetylcysteine (NAC) pretreatment in the prevention of contrast-induced nephropathy (CIN). In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of NAC treatment for the prevention of CIN. METHODS AND RESULTS: PubMed, EMBASE, and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk (RR) and corresponding 95% CI for incident CIN were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of CIN. The incidence of CIN was 12.8% in the NAC group versus 16.0% in the control group (RR: 0.76, 95% CI: 0.66 0.88, P=0.0002). In the patients undergoing coronary angiography, the incidence of CIN in the NAC group versus the control group was 13.7% versus 17.2% (RR: 0.74, 95% CI: 0.63-0.87, P=0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% (RR: 1.00, 95% CI: 0.42-2.40, P=1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% (RR: 0.51, 95% CI: 0.29-0.89, P=0.02). CONCLUSIONS: Our meta-analysis showed an inverse and significant association between NAC supplementation and risk of CIN in patients undergoing coronary angiography and computed tomography, while a protective role for NAC in patients undergoing peripheral angiography was not obvious. PMID- 27663417 TI - Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding. AB - BACKGROUND & AIMS: Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known endoscopic pattern carrying a high-risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. METHODS: From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleed-free survival, overall survival and life-threatening complications of bleeding. RESULTS: High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis (p<0.001), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleed-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for non-cirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with non-cirrhotic causes and cirrhosis respectively. CONCLUSION: In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. LAY SUMMARY: In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the child's age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can be achieved by surgery or endoscopic treatment, and decreases mortality and morbidity. PMID- 27663418 TI - Non-invasive estimation of HVPG by combined structural and hemodynamic evaluation of portal hypertension using quantitative magnetic resonance imaging. PMID- 27663419 TI - Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease. AB - BACKGROUND & AIMS: To date, no pharmacological therapy has been approved for non alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the therapeutic potential of poly ADP-ribose polymerase (PARP) inhibitors in mouse models of NAFLD. METHODS: As poly ADP-ribosylation (PARylation) of proteins by PARPs consumes nicotinamide adenine dinucleotide (NAD+), we hypothesized that overactivation of PARPs drives NAD+ depletion in NAFLD. Therefore, we assessed the effectiveness of PARP inhibition to replenish NAD+ and activate NAD+-dependent sirtuins, hence improving hepatic fatty acid oxidation. To do this, we examined the preventive and therapeutic benefits of the PARP inhibitor (PARPi), olaparib, in different models of NAFLD. RESULTS: The induction of NAFLD in C57BL/6J mice using a high-fat high-sucrose (HFHS)-diet increased PARylation of proteins by PARPs. As such, increased PARylation was associated with reduced NAD+ levels and mitochondrial function and content, which was concurrent with elevated hepatic lipid content. HFHS diet supplemented with PARPi reversed NAFLD through repletion of NAD+, increasing mitochondrial biogenesis and beta-oxidation in liver. Furthermore, PARPi reduced reactive oxygen species, endoplasmic reticulum stress and fibrosis. The benefits of PARPi treatment were confirmed in mice fed with a methionine- and choline-deficient diet and in mice with lipopolysaccharide-induced hepatitis; PARP activation was attenuated and the development of hepatic injury was delayed in both models. Using Sirt1hep-/- mice, the beneficial effects of a PARPi-supplemented HFHS diet were found to be Sirt1-dependent. CONCLUSIONS: Our study provides a novel and practical pharmacological approach for treating NAFLD, fueling optimism for potential clinical studies. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the Western world and has no approved pharmacological therapy. PARP inhibitors given as a treatment in two different mouse models of NAFLD confer a protection against its development. PARP inhibitors may therefore represent a novel and practical pharmacological approach for treating NAFLD. PMID- 27663421 TI - Serum uric acid as prognostic marker of coronary heart disease (CHD). AB - BACKGROUND: A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardio vascular and renal diseases especially in patients with diabetes mellitus, hypertension. Hyperuricemia is a risk factor of coronary heart disease. Several studies showed positive association between hyperuricemia and CHD risk factors. OBJECTIVE: To analyze the serum uric acid levels in patients with diabetes and hypertension, which helps in understanding its role as prognostic marker of coronary heart disease. METHOD: The study was conducted in population of Wadi-Al Dawasir (K.S.A.) aged 20-80 years through random sampling from October 2012 to June 2013. It included 250 samples and the cases were categorized into diabetic and hypertensive. In the cases, purely hypertensive were 52, diabetic were 57 and mixed group included both diabetic and hypertensive patients 65. Fasting blood was collected to analyze lipid profile which included (total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein) and serum uric acid in association with age and heredity was also studied. Patient demographics were recorded. RESULTS: The study revealed significant association of serum uric acid (p<0.014*) and total cholesterol (p<0.007**) triglycerides (p<0.009**) low density lipoprotein (p<0.044*) in hypertensive group. Serum uric acid levels in the mixed group patients with diabetes and hypertension reported serum uric acid (p<0.0037), total cholesterol (p<0.089+) proved to have increased risk of coronary heart disease. When compared to controls (non-diabetic p<0.529) and (non-hypertensive p<0.021*) with respect to serum uric acid levels show the magnitude of risk to coronary heart disease. With progressing age the association of lipid profile and serum uric acid reported (p<0.001**) in diabetics. CONCLUSION: Significant correlations were found between serum uric acid and risk factors for CHD. This is first study of its kind in this region of K.S.A., which helps the community to understand the role of serum uric acid in coronary heart disease, justifies the objective of research in taking preventive measures to combat the deleterious effect of coronary heart disease. Prevention and early detection of elevated uric acid in both hypertensive and diabetic patients could serve as effective investigative tool in reducing coronary heart disease. PMID- 27663422 TI - CcpNmr AnalysisAssign: a flexible platform for integrated NMR analysis. AB - NMR spectroscopy is an indispensably powerful technique for the analysis of biomolecules under ambient conditions, both for structural- and functional studies. However, in practice the complexity of the technique has often frustrated its application by non-specialists. In this paper, we present CcpNmr version-3, the latest software release from the Collaborative Computational Project for NMR, for all aspects of NMR data analysis, including liquid- and solid-state NMR data. This software has been designed to be simple, functional and flexible, and aims to ensure that routine tasks can be performed in a straightforward manner. We have designed the software according to modern software engineering principles and leveraged the capabilities of modern graphics libraries to simplify a variety of data analysis tasks. We describe the process of backbone assignment as an example of the flexibility and simplicity of implementing workflows, as well as the toolkit used to create the necessary graphics for this workflow. The package can be downloaded from www.ccpn.ac.uk/v3 software/downloads and is freely available to all non-profit organisations. PMID- 27663420 TI - New Insights into Protein Hydroxylation and Its Important Role in Human Diseases. AB - Protein hydroxylation is a post-translational modification catalyzed by 2 oxoglutarate-dependent dioxygenases. The hydroxylation modification can take place on various amino acids, including but not limited to proline, lysine, asparagine, aspartate and histidine. A classical example of this modification is hypoxia inducible factor alpha (HIF-alpha) prolyl hydroxylation, which affects HIF-alpha protein stability via the Von-Hippel Lindau (VHL) tumor suppressor pathway, a Cullin 2-based E3 ligase adaptor protein frequently mutated in kidney cancer. In addition to protein stability regulation, protein hydroxylation may influence other post-translational modifications or the kinase activity of the modified protein (such as Akt and DYRK1A/B). In other cases, protein hydroxylation may alter protein-protein interaction and its downstream signaling events in vivo (such as OTUB1, MAPK6 and eEF2K). In this review, we highlight the recently identified protein hydroxylation targets and their pathophysiological roles, especially in cancer settings. Better understanding of protein hydroxylation will help identify novel therapeutic targets and their regulation mechanisms to foster development of more effective treatment strategies for various human cancers. PMID- 27663424 TI - Testosterone may increase rat anterior cruciate ligament strength. AB - BACKGROUND: Women are more likely than men to injure the anterior cruciate ligament (ACL). Human and animal trials have linked circulating estradiol to injury rate and ligament strength. Fewer studies have examined the role of testosterone. The purpose of this study was to determine if male rats with normal testosterone levels would have stronger ACLs than castrated rats. METHODS: Eight castrated (group C) and eight normal (group N) 12-week-old, male Sprague-Dawley rats were used for the study. Mean testosterone levels were 0.14ng/mL (95% CI: 0.10 to 0.17) in group C and 3.54ng/mL (95% CI: 1.32 to 5.76) in group N. After euthanasia, ACL cross-sectional area was calculated, and a servohydraulic material testing unit was used to measure ligament properties. RESULTS: Specimens from both groups had similar cross-sectional area, but N specimens showed greater mean load-to-failure (34.5N [95% CI: 31.6 to 37.4] vs 29.2N [95% CI: 27.9 to 30.6]) and ultimate stress (38.7MPa [95% CI: 34.1 to 43.3] vs 31.8MPa [95% CI: 29.8 to 33.8]). Mean energy was 27.7mJ (95% CI: 23.1 to 32.2) in the N group and 23.4mJ (95% CI: 18.2 to 28.6) in the C group. CONCLUSIONS: Rats with normal circulating testosterone had higher ACL load-to-failure and ultimate stress, indicating that testosterone may influence ACL strength and the injury rate of the ligament. PMID- 27663425 TI - Intraepithelial lymphocytes subsets in different forms of celiac disease. AB - AIM: The enumeration of intraepithelial lymphocytes subsets (total, gammadelta, and CD3(-) IELs) by flow cytometry (FCM), named as IEL lymphogram, constitutes a useful tool for celiac disease (CD) diagnosis. The aim of this study was to quantify IELs by FCM and their diagnostic value to differentiate active, silent and potential CD. METHODS: Prospective study of 60 active and 20 silent CD patients, and 161 controls in which duodenal biopsy and IEL quantification by FCM was performed. RESULTS: Active and silent CD patients had significant higher levels of both total and gammadelta IELs than absent CD patients (P < 0.0001 and P < 0.0001, P = 0.012 and P < 0.011; respectively). Active and silent CD patients had significant lower levels of CD3(-) IELs than absent CD patients (P < 0.047 and P < 0.009, respectively). Moreover, they were lower in silent than in active CD patients (P = 0.002). Changes of IELs subsets were more marked in children than adults active CD. The optimal IEL lymphogram cut off values for active CD diagnosis were: >=10, >=15 and <=9 %, and with better performance characteristics for silent CD: >= 11, >=10 and <=5 %. CONCLUSION: The evaluation of IELs subsets by FCM is useful to confirm diagnosis of active and silent CD. PMID- 27663423 TI - Robotic and open partial nephrectomy for localized renal tumors larger than 7 cm: a single-center experience. AB - PURPOSE: To compare perioperative outcomes between robotic partial nephrectomy and open partial nephrectomy for localized >7 cm tumors. METHODS: We identified patients in our institutional review boards approved database who underwent robotic partial nephrectomy or open partial nephrectomy for treatment of renal tumors >7 cm in size between January 2009 and August 2015. The operative postoperative outcomes and complications were compared between groups. RESULTS: The number of patients with >7 cm renal tumors treated at our center with robotic partial nephrectomy and open partial nephrectomy were 54 and 56, respectively. Patients' demographics and tumor characteristics were similar between groups. Likewise, there were no significant difference between the groups in duration of operation, positive surgical margin rates and incidence of malignant disease rates. Median ischemia time was lower in robotic partial nephrectomy group (31.5 vs. 35 min., p = 0.02). Patients undergoing robotic partial nephrectomy had significantly lower intraoperative blood transfusion rates (9.4 vs. 30.4 %, p = 0.008) and shorter length of hospital stay (3.5 vs. 5.3 days, p < 0.001). The incidence of overall complications (robotic arm, 18.5 % vs. open arm, 28.6 %, p = 0.26) and major complications (robotic arm, 3.7 % vs. open arm, 12.5 %, p = 0.16) was comparable between the two groups. The readmission rate within 30-days after discharge was higher in open partial nephrectomy group (p = 0.03). There was no difference in the median percentage estimated glomerular filtration rate preservation and chronic kidney disease upstaging between groups. CONCLUSIONS: Localized renal tumors >7 cm and amenable to partial nephrectomy can be considered suitable for robotic approach. PMID- 27663427 TI - Prevalence, co-occurrence, and clustering of health-risk behaviors among people with different socio-economic trajectories: A population-based study. AB - Only a few previously published studies have investigated the co-occurrence and clustering of health-risk behaviors in people with different socio-economic trajectories from childhood to adulthood. This study was based on data collected through the Stockholm County Council's public health surveys. We selected the 24,241 participants aged 30 to 65years, who responded to a postal questionnaire in 2010. Information on parents' and participants' educational levels was used for classification of four socio-economic trajectories, from childhood to adulthood: the 'stable high', the 'upwardly mobile', the 'downwardly mobile', and the 'stable low'. Information on daily smoking, risky drinking, physical inactivity, and poor diet was used for assessment of health-risk behaviors: their prevalence, co-occurrence, and clustering. We found all health-risk behaviors to be more prevalent among women and men with a downwardly mobile or stable low socio-economic trajectory. Accordingly, having three or four co-occurring health risk behaviors were much more likely (up to 4 times, in terms of odds ratios) in these groups as compared to the women and men with an upwardly mobile or a stable high socio-economic trajectory. However, clustering of the health-risk behaviors was not found to be stronger in those with a downwardly mobile or stable low socio-economic trajectory. Thus, the fact that women and men with a disadvantageous socio-economic career were found to have co-occurring health-risk behaviors more often than people with an advantageous socio-economic career seemed to be generated by differences in prevalence of the health-risk behaviors, not by differences in clustering of the behaviors. PMID- 27663426 TI - Impact of physical activity category on incidence of cardiovascular disease: Results from the 10-year follow-up of the ATTICA Study (2002-2012). AB - The aim of the study was to examine the effects of physical activity (PA) level on 10-year cardiovascular disease (CVD) incidence, taking into consideration several clinical and lifestyle risk factors along with the potential moderating role of gender. An analysis was undertaken on data from the ATTICA prospective cohort study (10-year follow-up, 2002-2012), which followed a Greek adult population (aged 18-89years). A total n=317 of fatal and nonfatal CVD events occurred among the 2020 participants. After adjusting for the lifestyle and clinical risk factors as potential confounders, odds ratio (ORs) of CVD risk of individuals who reported being sufficiently active and highly active were decreased by 58% (95% CI: 0.30, 0.58) and 70% (95% CI: 0.15, 0.56), when compared to those who were inactive/insufficiently active, respectively. Men had nearly two-fold increase in risk of CVD (95% CI: 1.62, 2.18) versus women. Stratified analysis by gender, revealed that sufficiently active men, had 52% (95% CI: 0.24, 0.97) reduced risk of CVD incidence when compared to inactive males, while, for women, the role of PA lost significance following adjusting for lifestyle factors. The current data suggests a beneficial effect of even moderate physical activity levels on 10-year incidence of CVD, reinforcing the importance of physically activity, especially for men. PMID- 27663428 TI - GIS-measured walkability, transit, and recreation environments in relation to older Adults' physical activity: A latent profile analysis. AB - An infrequently studied question is how diverse combinations of built environment (BE) features relate to physical activity (PA) for older adults. We derived patterns of geographic information systems- (GIS) measured BE features and explored how they accounted for differences in objective and self-reported PA, sedentary time, and BMI in a sample of older adults. Senior Neighborhood Quality of Life Study participants (N=714, aged 66-97years, 52.1% women, 29.7% racial/ethnic minority) were sampled in 2005-2008 from the Seattle-King County, WA and Baltimore, MD-Washington, DC regions. Participants' home addresses were geocoded, and net residential density, land use mix, retail floor area ratio, intersection density, public transit density, and public park and private recreation facility density measures for 1-km network buffers were derived. Latent profile analyses (LPAs) were estimated from these GIS-based measures. In multilevel regression models, profiles were compared on accelerometer-measured moderate-to-vigorous PA (MVPA) and sedentary time and self-reported PA, adjusting for covariates and clustering. Analyses were conducted in 2014-2015. LPAs yielded three profiles: low walkability/transit/recreation (L-L-L); mean walkability/transit/recreation (M-M-M); and high walkability/transit/recreation (H-H-H). Three PA outcomes were more favorable in the HHH than the LLL profile group (difference of 7.2min/day for MVPA, 97.8min/week for walking for errands, and 79.2min/week for walking for exercise; all ps<0.02). The most and least activity-supportive BE profiles showed greater differences in older adults' PA than did groupings based solely on a 4-component walkability index, suggesting that diverse BE features are important for healthy aging. PMID- 27663431 TI - "Can we walk?" Environmental supports for physical activity in India. AB - India is currently facing a non-communicable disease epidemic. Physical activity (PA) is a preventative factor for non-communicable diseases. Understanding the role of the built environment (BE) to facilitate or constrain PA is essential for public health interventions to increase population PA. The objective of this study was to understand BEs associations with PA occurring in two major life domains or life areas-travel and leisure-in urban India. Between December 2014 and April 2015, in-person surveys were conducted with participants (N=370; female=47.2%) in Chennai, India. Perceived BE characteristics regarding residential density, land use mix-diversity, land use mix-access, street connectivity, infrastructure for walking and bicycling, aesthetics, traffic safety, and safety from crime were measured using the adapted Neighborhood Environment Walkability Scale-India (NEWS-India). Self-reported PA was measured the International Physical Activity Questionnaire. High residential density was associated with greater odds of travel PA (aOR=1.9, 95% CI=1.2, 3.2). Land use mix-diversity was positively related to travel PA (aOR=2.1, 95%CI=1.2, 3.6), but not associated with leisure or total PA. The aggregate NEWS-India score predicted a two-fold increase in odds of travel PA (aOR=1.9, 95% CI=1.1, 3.1) and a 40% decrease in odds of leisure PA (aOR=0.6, 95% CI=0.4, 1.0). However, the association of the aggregated score with leisure PA was not significant. Results suggest that relationships between BE and PA in low-and-middle income countries may be context-specific, and may differ markedly from higher income countries. Findings have public health implications for India suggesting that caution should be taken when translating evidence across countries. PMID- 27663429 TI - The interaction between systemic inflammation and psychosocial stress in the association with cardiac troponin elevation: A new approach to risk assessment and disease prevention. AB - We have previously shown that there is a complex and dynamic biological interaction between acute mental stress and acute release of inflammatory factors into the blood stream in relation to heart disease. We now hypothesize that the presence of chronic psychosocial stress may modify the weight of single test results for inflammation as a predictor of heart disease. Using a cross-sectional design, 500 participants free from heart disease drawn from the Whitehall II study in UK in 2006-2008 were tested for plasma fibrinogen as an inflammatory factor, financial strain as a marker of chronic psychosocial stress, coronary calcification measured using computed tomography, and for plasma high-sensitivity cardiac troponin T (HS-CTnT) as a marker of cardiac risk. Fibrinogen concentration levels above the average were associated with a 5-fold increase in the odds of HS-CTnT positivity only among individuals with financial strain (N=208, OR=4.73, 95%CI=1.67 to 13.40, P=0.003). Fibrinogen was in fact not associated with HS-CTnT positivity in people without financial strain despite the larger size of that subsample (n=292, OR=0.84, 95%CI=0.42 to 1.67, P=0.622). A test for interaction on the full sample (N=500) showed a P value of 0.010 after adjusting for a range of demographics, health behaviours, traditional cardiovascular risk factors, psychosocial stressors, inflammatory cytokines, and coronary calcification. In conclusion, elevated fibrinogen seems to be cardio toxic only when is combined with financial strain. Chronic psychosocial stress may modify the meaning that we should give to single test results for inflammation. Further research is needed to confirm our results. PMID- 27663430 TI - Suicide in older men: The health in men cohort study (HIMS). AB - Suicide rates are high in later life, particularly among older men. Mood disorders are known risk factors, but the risk of suicide associated with poor physical health remains unclear. We completed a cohort study of a community representative sample of 38,170 men aged 65-85 in 1996 who were followed for up to 16years. Data on suicide attempts and completion were obtained from the Western Australia Data Linkage System, as was information about medical and mental health diagnoses. 240 (0.6%) participants had a recorded history of past suicide attempt, most commonly by poisoning (85%). Sixty-nine men died by suicide during follow up (0.3% of all deaths), most often by hanging (50.7%). Age adjusted competing risk regression showed that past suicide attempt was not a robust predictor of future suicide completion (sub-hazard ratio, SHR=1.58, 95% CI=0.39, 6.42), but bipolar (SHR=7.82, 95% CI=3.08, 19.90), depressive disorders (SHR=2.26, 95% CI=1.14, 4.51) and the number of health systems affected by disease (SHR for 3-4 health systems=6.02, 95% CI=2.69, 13.47; SHR for >=5 health systems=11.18, 95% CI=4.89, 25.53) were. The population fraction of suicides attributable to having 5 or more health systems affected by disease was 79% (95% CI=57%, 90%), and for any mood disorder (bipolar or depression) it was 17% (95% CI=3%, 28%). Older Australian men with multiple health morbidities have the highest risk of death by suicide, even after taking into account the presence of mood disorders. Improving the overall health of the population may be the most effective way of decreasing the rates of suicide in later life. PMID- 27663432 TI - Waist circumference, body mass index and waist-height ratio: Are two indices better than one for identifying hypertension risk in older adults? AB - OBJECTIVE: To investigate if the combination of Waist Circumference (WC) and Body Mass Index (BMI) or Waist to Height Ratio (WHtR) and BMI measures is superior to the separate indicators in identifying hypertension risk in older adults from southern Brazil. METHOD: This cross-sectional study analyzed data from the second wave (2013/14) of a population- and household-based survey carried out with 1197 older adults (778 women). Hypertension (i.e., outcome) was identified by self report. The independent variables were body mass index (BMI>=27kg/m2), waist circumference (WC>=88cm for women and WC>=102cm for men), waist/height ratio (WHtR>=0.5), and the combined indexes BMI+WC (BMI>=27kg/m2+WC>=88cm for women and WC>=102cm for men) and BMI+WHtR (BMI>=27kg/m2+WHtR>=0.5). The associations were explored using binary logistic regression. RESULTS: The results showed sex differences in all study characteristics. In women, all indicators were associated with the outcome, after adjustments (age, race/color, marital status, schooling, smoking, alcohol consumption, physical activity, and diabetes). WHtR was the indicator most strongly associated with hypertension (OR=2.97; 95% CI 1.58 to 5.59). For men, only BMI and the combined indicators were associated with hypertension. Combined measures of BMI+WHtR showed a stronger association with the outcome (OR=2.68; IC95% 1.62 to 4.44). CONCLUSION: The associated indicators differed between the sexes. The combination of BMI+WC and BMI+WHtR using current cut-off points may provide an improved measure of hypertension risk. PMID- 27663434 TI - Prognostic value of endocrine treatment-related symptoms in patients with breast cancer: a meta-analysis. AB - PURPOSE: Endocrine therapy is associated with improved disease-free survival (DFS) in hormone receptor-positive breast cancer, but it is also associated with many adverse events. The aim of this study was to clarify the association between endocrine treatment-related symptoms and treatment efficacy in patients receiving adjuvant endocrine therapy. METHOD: EMBASE, Web of Science, PubMed, and CENTRAL databases were searched for studies that compared treatment efficacy between patients in whom adverse events did and did not occur during hormone therapy. Hazard ratios (HRs) and associated 95 % confidence intervals (CIs) for DFS and overall survival were estimated and pooled using random-effects models. RESULTS: Of 4665 citations identified, ten studies incorporating 32,192 patients were included in the meta-analysis. The presence of endocrine treatment-related symptoms was associated with improved DFS (HR 0.76; 95 % CI 0.68-0.85). Similar results were observed in patients with vasomotor symptoms (HR 0.76; 95 % CI 0.66 0.87) or musculoskeletal symptoms (HR 0.75; 95 % CI 0.60-0.94), in patients taking an aromatase inhibitor (HR 0.69; 95 % CI 0.57-0.85) or tamoxifen (HR 0.74; 95 % CI 0.60-0.93), and in patients with symptoms at 3-month (HR 0.74; 95 % CI 0.66-0.83), 6-month (HR 0.80; 95 % CI 0.66-0.96), or 12-month follow-up visits (HR 0.75; 95 % CI 0.68-0.83). However, no significant difference in overall survival was observed between patients with or without endocrine treatment related symptoms (HR 0.82; 95 % CI 0.60-1.11). Sensitivity analysis excluding studies with heterogeneous factors yielded consistent results. No evidence of publication bias was observed. CONCLUSION: In our meta-analysis, endocrine treatment-related symptoms were shown to correlate with superior DFS and may therefore be useful in predicting treatment efficacy in patients with breast cancer receiving hormone therapy. PMID- 27663435 TI - Treatment with aromatase inhibitors and markers of cardiovascular disease. AB - PURPOSE: The cardiovascular effects of estrogen deprivation induced by aromatase inhibitors are unknown. We carried out a cross-sectional study to evaluate the effect of estrogen deprivation induced by aromatase inhibitors on markers of cardiovascular risk. METHODS: We enrolled 410 postmenopausal women: 200 consecutive breast cancer patients treated with aromatase inhibitors for a median of 53 months (range 23-122) and 210 volunteer controls. Carotid intima-media thickness, presence of carotid stenosis, and presence of abdominal aortic aneurism were evaluated through an ultrasound examination. RESULTS: Average carotid intima-media thickness was 0.97 +/- 0.02 mm and 1.08 +/- 0.02 mm for breast cancer group and control group, respectively (p < 0.005). The incidence of carotid stenosis in the two groups was similar: 24.2 % in the breast cancer group and 28.6 % in the control group (OR 0.80; 95 % CI 0.51-1.25; p = 0.32). No aneurismatic dilatation of the aorta was recorded. Average abdominal aortic diameter was 14.9 +/- 2.4 mm in the breast cancer group and 15.0 +/- 2.4 mm in the control group. CONCLUSIONS: Our study showed no association between treatment with aromatase inhibitors for five or less years and increased carotid intima media thickness and higher prevalence of carotid stenosis or abdominal aortic aneurism. The lack of impact on these markers suggests that cardiovascular risk is not increased by treatment with aromatase inhibitors. PMID- 27663437 TI - Portal vein thrombus and infiltrative HCC: a pictoral review. AB - Infiltrative hepatocellular carcinoma (HCC) can be overlooked on imaging. Radiologists should have a high index of suspicion for this entity in patients with chronic liver disease. Careful evaluation of the portal vein may help the radiologist diagnose infiltrative HCC, due to the high association (68%-100%) of portal vein tumor thrombus with this condition. This article will review the imaging findings of infiltrative HCC, particularly its association with portal vein thrombus, and describe imaging pitfalls and mimickers. PMID- 27663436 TI - Impact of androgen receptor expression in fluoxymesterone-treated estrogen receptor-positive metastatic breast cancer refractory to contemporary hormonal therapy. AB - PURPOSE: The purpose of this study is to evaluate survival outcome in patients with hormone receptor (HR)-positive (+) metastatic breast cancer (MBC) who received fluoxymesterone after disease progression while receiving contemporary hormonal therapy, as well as the association between estrogen receptor (ER)/androgen receptor (AR) status and survival outcome in these patients. METHODS: We retrospectively identified 103 patients treated with fluoxymesterone for HR + MBC from 2000 to 2014 and with at least one previous hormonal therapy in a metastatic setting. RESULTS: A median of 3 (range 1-10) hormonal therapies (aromatase inhibitors, tamoxifen, and/or fulvestrant) were received before fluoxymesterone; 33 patients discontinued fluoxymesterone before progression because of physician decision or adverse events including toxicity in 14 patients. Of the remaining 70 patients, 2 (3 %) had complete response, 7 (10 %) partial response, and 21 (30 %) stable disease for at least 6 months, yielding a clinical benefit rate of 43 %. The median PFS was 3.9 months (95 % CI 3.2-5.3 months). Multivariate analysis revealed no significant association between PFS and the type or number of prior systemic treatments. All 39 patients who had archived tumor slides available for AR staining had ER + carcinoma; 10 had >=1 % but <10 %, 18 had >=10 %, and 11 had no AR nuclear expression. AR positivity with various cutoffs (i.e. any AR + cells, >=1 % AR + cells, or >=10 % AR + cells) was not significantly associated with survival outcome. CONCLUSIONS: Fluoxymesterone can be considered for patients whose ER + MBC progresses on contemporary hormonal therapy, regardless of the level of AR expression. PMID- 27663438 TI - Health and Environmental Risks from Lead-based Ammunition: Science Versus Socio Politics. PMID- 27663439 TI - Histologic purity of signet ring cell carcinoma is a favorable risk factor for lymph node metastasis in poorly cohesive, submucosa-invasive early gastric carcinoma. AB - BACKGROUND: The prediction of biologic behavior of poorly cohesive early gastric carcinoma (EGC) is an important issue in the selection of the treatment modality. To elucidate the risk factors for lymph node metastasis (LNM) of poorly cohesive EGC, we focused on the histologic purity of the poorly cohesive component and evaluated the impact of this factor on LNM. METHODS: We divided poorly cohesive EGC into (1) pure signet ring cell (SRC) carcinoma, which was defined as composed only of signet ring cells or poorly cohesive cells and (2) mixed SRC carcinoma, defined as poorly cohesive carcinoma with minor tubular components. We reviewed the clinicopathologic features, including age, sex, location, size, depth, lymphovascular invasion (LVI), LNM, ulceration, and intestinal metaplasia between the two groups in a large series of poorly cohesive, submucosa-invasive EGC (n = 317). RESULTS: LNM was found in 58 cases (18.3 %). Mixed SRC carcinoma histologic type (p < 0.001), larger tumor size (more than 2 cm) (p = 0.012), and the presence of LVI (p < 0.001) were associated with LNM. Pure SRC carcinomas accounted for 56.2 % (178/317) of the cases. Fourteen pure SRC carcinomas (7.8 %) showed LNM, whereas 44 mixed SRC carcinomas (31.9 %) exhibited LNM (p < 0.001). On multivariate logistic regression, the presence of LVI (odds ratio 6.737; 95 % confidence interval 2.714-16.720; p < 0.001) and mixed SRC carcinoma histologic type (odds ratio 4.674; 95 % confidence interval 2.370-9.216; p < 0.001) were independent predictors of LNM in poorly cohesive, submucosa-invasive EGC. CONCLUSIONS: The presence of a tubular component in SRC carcinoma was a risk factor for LNM in poorly cohesive, submucosa-invasive EGC. On the basis of this finding, we propose that the presence of a minor tubular component or the purity of the poorly cohesive/SRC carcinoma component should be reported in daily pathologic practice. PMID- 27663440 TI - Rapid bioremediation of Alizarin Red S and Quinizarine Green SS dyes using Trichoderma lixii F21 mediated by biosorption and enzymatic processes. AB - In this study, a newly isolated ascomycete fungus Trichoderma lixii F21 was explored to bioremediate the polar [Alizarin Red S (ARS)] and non-polar [Quinizarine Green SS (QGSS)] anthraquinone dyes. The bioremediation of ARS and QGSS by T. lixii F21 was found to be 77.78 and 98.31 %, respectively, via biosorption and enzymatic processes within 7 days of incubation. The maximum biosorption (ARS = 33.7 % and QGSS = 74.7 %) and enzymatic biodegradation (ARS = 44.1 % and QGSS = 23.6 %) were observed at pH 4 and 27 degrees C in the presence of glucose and yeast extract. The laccase and catechol 1,2-dioxygenase produced by T. lixii F21 were involved in the molecular conversions of ARS and QGSS to phenolic and carboxylic acid compounds, without the formation of toxic aromatic amines. This study suggests that T. lixii F21 may be a good candidate for the bioremediation of industrial effluents contaminated with anthraquinone dyes. PMID- 27663441 TI - Characterization of neutrophils and macrophages from ex vivo-cultured murine bone marrow for morphologic maturation and functional responses by imaging flow cytometry. AB - Neutrophils and macrophages differentiate from common myeloid progenitors in the bone marrow, where they undergo nuclear morphologic changes during maturation. During this process, both cell types acquire critical innate immune functions that include phagocytosis of pathogens, and for neutrophils the release of nuclear material called nuclear extracellular traps (NETs). Primary cells used to study these functions are typically purified from mature mouse tissues, but bone marrow-derived ex vivo cultures provide more abundant numbers of progenitors and functionally mature cells. Routine analyses of these cells use conventional microscopy and flow cytometry, which present limitations; microscopy is laborious and subjective, whereas flow cytometry lacks spatial resolution. Here we describe methods to generate enriched populations of neutrophils or macrophages from cryopreserved mouse bone marrow cultured ex vivo, and to use imaging flow cytometry that combines the resolution of microscopy with flow cytometry to analyze cells for morphologic features, phagocytosis, and NETosis. PMID- 27663442 TI - Correlation of HIF-1alpha/HIF-2alpha expression with FDG uptake in lung adenocarcinoma. AB - OBJECTIVES: Hypoxia is a key element involved in the development and progression of tumors. HIF-1alpha may transiently induce and mediate the response to acute and severe hypoxia, while HIF-2alpha may induce a longer response and may control the response to chronic and moderate hypoxia. Hypoxia increases the cellular uptake of FDG. Therefore, HIF may play an important role in the process of the cellular uptake of FDG. The aim of this study was to compare HIF-1alpha/HIF 2alpha expression with FDG uptake, Glut-1 expression, and prognosis in the patients with lung adenocarcinoma and to investigate the role of HIF-1alpha/HIF 2alpha in the uptake of FDG in lung adenocarcinoma. METHODS: In the current work, we compared the immunohistochemical expression of HIF-1alpha and HIF-2alpha in surgical specimens of 44 patients with lung adenocarcinoma. The relationships between HIF-alpha expression and Glut-1 expression, FDG uptake, and clinicopathological factors, including prognosis, were analyzed. RESULTS: There was a marginal association between HIF-1alpha and HIF-2alpha expressions (P = 0.076). We found a significant correlation between HIF-2alpha expression and FDG uptake (P = 0.0001). HIF-1alpha expression showed a marginal association with FDG uptake (P = 0.066). FDG uptake correlated more significantly with HIF-2alpha expression than with HIF-1alpha expression. A significant correlation was noticed between Glut-1 expression and both HIF-1alpha and HIF-2alpha expressions (P = 0.005 and P = 0.003, respectively). Univariate analysis of disease-free survival demonstrated that FDG uptake and HIF-2alpha expression, but not HIF-1alpha expression, were related to recurrence (P < 0.0001). CONCLUSION: FDG uptake correlated more significantly with HIF-2alpha expression than with HIF-1alpha expression, and both FDG uptake and HIF-2alpha expression, but not HIF-1alpha expression was correlated with post-operative recurrence in the patients with lung adenocarcinoma. These results suggest that both FDG uptake and HIF-2alpha expression may represent a more aggressive phenotype and that HIF-2alpha may play a more important role than HIF-1alpha in the uptake of FDG in lung adenocarcinoma. PMID- 27663443 TI - A Watershed Analysis of Seasonal Concentration- and Loading-based Results for Escherichia coli in Inland Waters. AB - Fecal indicator bacteria, such as Escherichia coli, are frequently monitored in recreational waterbodies as indicators of potential fecal pathogen presence and exposure. The present watershed analysis investigated the influence of season on E. coli concentration (MPN/100 mL) and loading (MPN/day) measurements for inland waters at baseflow conditions. The master dataset collected during 2007-2012 for three watersheds included 896 E. coli (Colilert) samples with simultaneous flow taken for a subset (39 %) of samples. The outcomes for grouped watersheds were reflected in most cases for individual watersheds. Concentration- and loading based results were highest in summer and spring, and lowest in the winter and fall, respectively. The comparison of these two measurement techniques (concentration and loading) highlight the impact of flow data during baseflow conditions for inland waters and reveal that caution should be used when inferring one method's results from another. PMID- 27663445 TI - Bioaccumulation of Uranium and Thorium by Lemna minor and Lemna gibba in Pb-Zn-Ag Tailing Water. AB - This study focused on the ability of Lemna minor and Lemna gibba to remove U and Th in the tailing water of Keban, Turkey. These plants were placed in tailing water and individually fed to the reactors designed for these plants. Water and plant samples were collected daily from the mining area. The plants were ashed at 300 degrees C for 1 day and analyzed by ICP-MS for U and Th. U was accumulated as a function of time by these plants, and performances between 110 % and 483 % for L. gibba, and between 218 % and 1194 % for L. minor, were shown. The highest Th accumulations in L. minor and L. gibba were observed at 300 % and 600 % performances, respectively, on the second day of the experiment. This study indicated that both L. gibba and L. minor demonstrated a high ability to remove U and Th from tailing water polluted by trace elements. PMID- 27663444 TI - Fate of Potential Contaminants Due to Disposal of Olive Mill Wastewaters in Unprotected Evaporation Ponds. AB - The disposal of olive mill wastewaters (OMW) in shallow and unprotected evaporation ponds is a common, low-cost management practice, followed in Mediterranean countries. So far, the fate of potential soil pollutants in areas located near evaporation ponds is not adequately documented. This study investigates the extent in which the long-term disposal of OMW in evaporation ponds can affect the soil properties of the area located outside the evaporation pond and assesses the fate of the pollution loads of OMW. Four soil profiles situated outside and around the down slope side of the disposal area were excavated. The results showed considerable changes in concentration of soil phenols at the down-site soil profiles, due to the subsurface transport of the OMW. In addition, excessive concentrations of NH4+, PO43- and phenols were recorded in liquid samples taken from inside at the bottom of the soil profiles. It is concluded that unprotected evaporation ponds located in light texture soils pose a serious threat to favour soil and water pollution. PMID- 27663446 TI - Investigation on the Performance of Chemically Modified Aquatic Macrophytes Salvinia molesta for the Micro-Solid Phase Preconcentration of Cd(II) On-Line Coupled to FAAS. AB - In this study, a new method for the preconcentration of cadmium ions using modified aquatic macrophytes - Salvinia molesta as biosorbent in an on-line preconcentration system coupled to flame atomic absorption spectrometry (FAAS) was developed. The method is based on preconcentration of 20.0 mL sample at pH 3.75 through 35.0 mg of biosorbent at 10.0 mL min-1 and subsequent elution with 0.5 mol L-1 HNO3. A preconcentration factor of 31-fold, linear dynamic range from 5.0 to 70.0 ug L-1 (r = 0.9996) and detection and quantification limits of 0.15 and 0.51 ug L-1 were obtained. The characterization of the biosorbent chemically modified with NaOH and citric acid, was performed through FTIR and SEM measurements. The method precision was found to be 3.97 % and 1.48 % for 5.0 and 60.0 ug L-1 Cd(II) solutions, respectively. The applicability of method was checked by analysis of different kind of water samples and certified reference material. PMID- 27663447 TI - Australian Gay Men Describe the Details of Their HIV Infection Through a Cross Sectional Web-Based Survey. AB - BACKGROUND: With emerging opportunities for preventing human immunodeficiency virus (HIV) transmission, it remains important to identify those at greatest risk of infection and to describe and understand the contexts in which transmissions occur. Some gay and bisexual men with recently diagnosed HIV infection are initially unable to identify high-risk behaviors that would explain their HIV infection. We explored whether Web-based data collection could assist them in identifying the circumstances of their infection. OBJECTIVE: To assess the capacity of a Web-based survey to collect reliable self-report data on the event to which gay and bisexual men ascribe their HIV infection. METHODS: The HIV Seroconversion Study included a Web-based survey of gay and bisexual men with recently diagnosed HIV infection in Australia. Participants were asked if they could identify and describe the event they believe led to their infection. Men were also asked about their sexual and other risk practices during the 6 months before their diagnosis. RESULTS: Most (403/506, 79.6%) gay and bisexual men with newly diagnosed HIV infection were able to identify and describe the circumstances that likely led to their infection. Among those who were initially unable to identify possible exposure events, many could nonetheless provide sensible information that ostensibly explained their seroconversion. Free-text responses allowed men to provide more detailed and contextual information, whereas questions about the totality of their sexual behavior before diagnosis provided opportunities for men to describe their sexual risk behavior in general. Overall, 84.0% indicated having engaged in condomless anal intercourse before their HIV diagnosis, including 71.8% in the receptive position. CONCLUSIONS: This study demonstrates the effectiveness of using Internet-based technologies to capture sensitive information about the circumstances in which HIV infection occurs among gay and bisexual men. By providing a range of opportunities for relaying experience, this research reveals some of the complexity in how individuals come to understand and explain their HIV infection. These findings may assist in obtaining detailed sexual history in the clinical setting. PMID- 27663448 TI - Low Pressure Tolerance by Methanogens in an Aqueous Environment: Implications for Subsurface Life on Mars. AB - The low pressure at the surface of Mars (average: 6 mbar) is one potentially biocidal factor that any extant life on the planet would need to endure. Near subsurface life, while shielded from ultraviolet radiation, would also be exposed to this low pressure environment, as the atmospheric gas-phase pressure increases very gradually with depth. Few studies have focused on low pressure as inhibitory to the growth or survival of organisms. However, recent work has uncovered a potential constraint to bacterial growth below 25 mbar. The study reported here tested the survivability of four methanogen species (Methanothermobacter wolfeii, Methanosarcina barkeri, Methanobacterium formicicum, Methanococcus maripaludis) under low pressure conditions approaching average martian surface pressure (6 mbar - 143 mbar) in an aqueous environment. Each of the four species survived exposure of varying length (3 days - 21 days) at pressures down to 6 mbar. This research is an important stepping-stone to determining if methanogens can actively metabolize/grow under these low pressures. Additionally, the recently discovered recurring slope lineae suggest that liquid water columns may connect the surface to deeper levels in the subsurface. If that is the case, any organism being transported in the water column would encounter the changing pressures during the transport. PMID- 27663449 TI - Effects of Glycine, Water, Ammonia, and Ammonium Bicarbonate on the Oligomerization of Methionine. AB - The abiotic oligomerization of amino acids may have created primordial, protein like biological catalysts on the early Earth. Previous studies have proposed and evaluated the potential of diagenesis for the amino acid oligomerization, simulating the formation of peptides that include glycine, alanine, and valine, separately. However, whether such conditions can promote the formation of peptides composed of multiple amino acids remains unclear. Furthermore, the chemistry of pore water in sediments should affect the oligomerization and degradation of amino acids and oligomers, but these effects have not been studied extensively. In this study, we investigated the effects of water, ammonia, ammonium bicarbonate, pH, and glycine on the oligomerization and degradation of methionine under high pressure (150 MPa) and high temperature conditions (175 degrees C) for 96 h. Methionine is more difficult to oligomerize than glycine and methionine dimer was formed in the incubation of dry powder of methionine. Methionine oligomers as long as trimers, as well as methionylglycine and glycylmethionine, were formed under every condition with these additional compounds. Among the compounds tested, the oligomerization reaction rate was accelerated by the presence of water and by an increase in pH. Ammonia also increased the oligomerization rate but consumed methionine by side reactions and resulted in the rapid degradation of methionine and its peptides. Similarly, glycine accelerated the oligomerization rate of methionine and the degradation of methionine, producing water, ammonia, and bicarbonate through its decomposition. With Gly, heterogeneous dimers (methionylglycine and glycylmethionine) were formed in greater amounts than with other additional compounds although smaller amount of these heterogeneous dimers were formed with other additional compounds. These results suggest that accelerated reaction rates induced by water and co existing reactive compounds promote the oligomerization of less reactive amino acids during diagenesis and enhance the formation of peptides composed of multiple amino acids. PMID- 27663450 TI - Prebiotic Synthesis of Glycine from Ethanolamine in Simulated Archean Alkaline Hydrothermal Vents. AB - Submarine hydrothermal vents are generally considered as the likely habitats for the origin and evolution of early life on Earth. In recent years, a novel hydrothermal system in Archean subseafloor has been proposed. In this model, highly alkaline and high temperature hydrothermal fluids were generated in basalt hosted hydrothermal vents, where H2 and CO2 could be abundantly provided. These extreme conditions could have played an irreplaceable role in the early evolution of life. Nevertheless, sufficient information has not yet been obtained for the abiotic synthesis of amino acids, which are indispensable components of life, at high temperature and alkaline condition. This study aims to propose a new method for the synthesis of glycine in simulated Archean submarine alkaline vent systems. We investigated the formation of glycine from ethanolamine under conditions of high temperature (80-160 degrees C) and highly alkaline solutions (pH = 9.70). Experiments were performed in an anaerobic environment under mild pressure (0.1-8.0 MPa) at the same time. The results suggested that the formation of glycine from ethanolamine occurred rapidly and efficiently in the presence of metal powders, and was favored by high temperatures and high pressures. The experiment provides a new pathway for prebiotic glycine formation and points out the phenomenal influence of high-temperature alkaline hydrothermal vents in origin of life in the early ocean. PMID- 27663451 TI - A randomized comparison between intravenous and perineural dexamethasone for ultrasound-guided axillary block. AB - BACKGROUND: This randomized double-blinded trial compared the effect of intravenous and perineural dexamethasone (8 mg) on the duration of motor block for ultrasound (US)-guided axillary brachial plexus block (AXB). METHODS: Patients undergoing upper limb surgery with US-guided AXB were randomly allocated to receive preservative-free dexamethasone (8 mg) via intravenous (n = 75) or perineural (n = 75) administration. The local anesthetic agent, 1% lidocaine 0.25% bupivacaine (30 mL) with epinephrine 5 ug.mL-1, was identical in all subjects. Operators and patients were blinded to the nature of the intravenous and perineural injectate. A blinded observer assessed the block success rate (i.e., a minimal sensorimotor composite score of 14 out of 16 points at 30 min), block onset time, as well as the presence of surgical anesthesia. Postoperatively, the blinded observer contacted all patients with successful blocks to record the duration of motor block (primary outcome), sensory block, and postoperative analgesia. RESULTS: No intergroup differences were observed in terms of success rate, surgical anesthesia, and block onset time. Compared to intravenous administration, perineural dexamethasone provided longer mean (SD) durations for motor block [17.5 (4.6) hr vs 12.8 (4.5) hr; mean difference, 4.6 hr; 95% confidence interval [CI], -6.21 to -3.08; P < 0.001], sensory block [17.7 (5.1) hr vs 13.7 (5.0) hr; mean difference, 4.0 hr; 95% CI, -5.77 to -2.27; P < 0.001], and postoperative analgesia [21.1 (4.6) hr vs 17.1 (4.6) hr; mean difference, 4.0 hr; 95% CI, -5.70 to -2.30; P < 0.001]. CONCLUSION: Compared to intravenous dosing, perineural dexamethasone (8 mg) results in longer durations of sensorimotor block and postoperative analgesia for ultrasound-guided axillary block. This trial was registered at www.clinicaltrials.gov number, NCT02629835. PMID- 27663452 TI - Perceptions of purpose, value, and process of the mini-Clinical Evaluation Exercise in anesthesia training. AB - INTRODUCTION: Workplace-based assessment is integral to programmatic assessment in a competency-based curriculum. In 2013, one such assessment, a mini-Clinical Evaluation Exercise (mini-CEX) with a novel "entrustability scale", became compulsory for over 1,200 Australia and New Zealand College of Anaesthetists (ANZCA) trainees. We explored trainees' and supervisors' understanding of the mini-CEX, their experience with the assessment, and their perceptions of its influence on learning and supervision. METHODS: We conducted semi-structured telephone interviews with anesthesia supervisors and trainees and performed an inductive thematic analysis of the verbatim transcripts. RESULTS: Eighteen supervisors and 17 trainees participated (n = 35). Interrelated themes concerned the perceived purpose of the mini-CEX, its value in trainee learning and supervision, and the process of performing the assessment. While few participants saw the mini-CEX primarily as an administrative burden, most focused on its potential for facilitating trainee improvement and reported positive impacts on the quantity and quality of feedback, trainee learning, and supervision. Finding time to schedule assessments and deliver timely feedback proved to be difficult in busy clinical workplaces. Views on case selection were divided and driven by contrasting goals - i.e., receiving useful feedback on challenging cases or receiving a high score by choosing lenient assessors or easy cases. Whether individual mini-CEXs were summative or formative was subject to intense debate, while the intended summative use of multiple mini-CEXs in programmatic assessment was poorly understood. CONCLUSION: Greater clarity of purpose and consistency of time commitment are necessary to embed the mini-CEX in the culture of the workplace, to realize the full potential for trainee learning, and to reach decisions on trainee progression. PMID- 27663453 TI - Respiratory self-gated 3D UTE for lung imaging in small animal MRI. AB - PURPOSE: To investigate retrospective respiratory gating of three-dimensional ultrashort echo time (3D UTE) lung acquisition in free-breathing rats using k space center self gating signal (DC-SG) and 3D image-based SG (3D-Img-SG). METHODS: Seven rats were investigated with a quasi-random 3D UTE protocol. Low resolution time-resolved sliding-window images were reconstructed with a 3D golden-angle radial sparse parallel (GRASP) reconstruction to extract a 3D-Img-SG signal, whereas DC-SG was extracted from the center of k-space. Both signals were sorted into 10 respiratory bins. Signal-to-noise ratio (SNR) and normalized signal intensity (NSI) in lung parenchyma, image sharpness, and lung volume changes were studied in the resulting images to show feasibility of the method. An algorithm for bulk movement identification and removal was implemented. RESULTS: Three-dimensional Img-SG allows reconstruction of different respiratory stages in all acquired datasets, showing clear differences in diaphragm position and significantly different lung volumes, SNR, and NSI in lung parenchyma. Improved sharpness in expiration images was observed compared to ungated images. DC-SG did not result in clear different diaphragm position in all cases. Bulk motion removal improved final image sharpness. CONCLUSION: Low-resolution 3D GRASP reconstruction allowed for extraction of an effective gating signal for 3D Img-SG. The DC-SG method did not work in cases for which respiratory frequencies were inconsistent. Magn Reson Med 78:739-745, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27663456 TI - Probable metronidazole induced serum sickness-like reaction in a paediatric patient. AB - WHAT IS KNOWN AND OBJECTIVE: Metronidazole (MTZ) is a commonly prescribed antibiotic and is generally well tolerated. To our knowledge, there has been only one case report linking MTZ with serum sickness-like reaction (SSLR). CASE SUMMARY: We report a probable case of SSLR following the administration of MTZ in a paediatric patient. WHAT IS NEW AND CONCLUSION: Serum sickness-like reaction may be associated with MTZ therapy, and this type of adverse drug reaction may be underreported in the literature. A prior case report and evaluation with the Naranjo algorithm indicating a 'probable' adverse drug reaction provide evidence to support this conclusion. PMID- 27663454 TI - Mice engrafted with human hematopoietic stem cells support a human myeloid cell inflammatory response in vivo. AB - Mice engrafted with human CD34+ hematopoietic stem and progenitor cells (CD34+ HSPCs) have been used to study human infection, diabetes, sepsis, and burn, suggesting that they could be highly amenable to characterizing the human inflammatory response to injury. To this end, human leukocytes infiltrating subcutaneous implants of polyvinyl alcohol (PVA) sponges were analyzed in immunodeficient NSG mice reconstituted with CD34+ -HSPCs. It was reported that human CD45+ (hCD45+ ) leukocytes were present in PVA sponges 3 and 7 days postimplantation and could be localized within the sponges by immunohistochemistry. The different CD45+ subtypes were characterized by flow cytometry and the profile of human cytokines they secreted into PVA wound fluid was assessed using a human-specific multiplex bead analyses of human IL-12p70, TNFalpha, IL-10, IL-6, IL1beta, and IL-8. This enabled tracking the functional contributions of HLA-DR+ , CD33+ , CD19+ , CD62L+ , CD11b+ , or CX3CR1+ hCD45+ infiltrating inflammatory leukocytes. PCR of cDNA prepared from these cells enabled the assessment and differentiation of human, mouse, and uniquely human genes. These findings support the hypothesis that mice engrafted with CD34+ HSPCs can be deployed as precision avatars to study the human inflammatory response to injury. PMID- 27663455 TI - P2X7R-dependent regulation of glycogen synthase kinase 3beta and claudin-18 in alveolar epithelial type I cells of mice lung. AB - The purinergic receptor P2X7 represents an ATP-gated ionotropic receptor with a selective localization in alveolar epithelial type I cells of the lung. Despite the involvement of the receptor in inflammatory processes of the lung, it is not established whether this receptor plays a specific role in the alveolar epithelial cell biology. There is evidence that P2X7 receptor influences Wnt/beta catenin signalling pathways in alveolar epithelial cells under conditions of injury. Here, we investigated the expression of GSK-3beta, a potent protein kinase involved in alveolar epithelial barrier functions, and of tight junction molecules occludin, claudin-4 and claudin-18 in wild-type and P2X7-/- mice. Western blot analysis, immunohistochemistry and quantitative real-time RT-PCR revealed a remarkable increase in claudin-18 mRNA and protein in lungs of P2X7-/- mice animals. Furthermore, alveolar epithelial cells from P2X7-/- animals showed decreased levels of GSK-3beta protein and its inactive form GSK-3beta (pS9). Conversely, claudin-18 knockout mice exhibited decreased P2X7 mRNA transcript abundance as measured by mRNA expression microarray and quantitative PCR. Our data are consistent with the hypothesis that P2X7R contributes to alveolar epithelial barrier function through effects on GSK-3beta. Furthermore, these data suggest a potential reciprocal regulation of claudin-18 and P2X7R in the alveolar epithelium. PMID- 27663457 TI - Exposure-QT analysis for sonidegib (LDE225), an oral inhibitor of the hedgehog signaling pathway, for measures of the QT prolongation potential in healthy subjects and in patients with advanced solid tumors. AB - PURPOSE: Sonidegib prevents activation of the Hedgehog signal transduction pathway. This PK-QT analysis has been performed to test for potential prolongation of the QT/QTc interval during extended use, and to understand the exposure-QT relationship for sonidegib in patients and in healthy volunteers (HV). METHODS: A pooled analysis of the change in QT interval corrected for heart rate according to Fridericia's formula was conducted across four patient studies from a total of 341 patients (n = 211, 102, 21, and 7 from the phase II pivotal study A2201, study X2101, study X1101, and study B2209, respectively), and across four healthy volunteer studies from a total of 204 healthy volunteers (n = 146, 36, 16, and 6 from study A2114, study A1102, study A2108, and study A2110, respectively). A PK/ECG subgroup of 62 patients from the pivotal study A2201 was also analyzed to assess the QT prolongation risk at steady-state exposures. Sonidigib PK and ECG data were matched to determine the change from baseline in QTcF using a linear mixed-effect model. RESULTS: Clinical data indicate sonidegib does not cause QTc prolongation. DeltaQTcF at steady-state concentrations for both 200 and 800-mg doses were all below 5 ms. The highest mean DeltaQTcF at steady state was -3.9 ms at week 17 pre-dose in the sonidegib 200-mg group and 2.7 ms at 2-h post-dose in the sonidegib 800-mg group. The upper one-sided 95 % confidence interval of the estimated DeltaQTcF at steady-state concentrations from the linear mixed-effect models were all <10 ms. No cases of ventricular arrhythmia or torsades de pointes and no deaths associated with QT prolongation have been reported in the sonidegib clinical development program. CONCLUSIONS: Based on these analyses, there is no evidence of QT prolongation associated with sonidegib 200 or 800 mg in solid tumor patients and HV. PMID- 27663458 TI - Combinatorial identification of DNA methylation patterns over age in the human brain. AB - BACKGROUND: DNA methylation plays a key role in developmental processes, which is reflected in changing methylation patterns at specific CpG sites over the lifetime of an individual. The underlying mechanisms are complex and possibly affect multiple genes or entire pathways. RESULTS: We applied a multivariate approach to identify combinations of CpG sites that undergo modifications when transitioning between developmental stages. Monte Carlo feature selection produced a list of ranked and statistically significant CpG sites, while rule based models allowed for identifying particular methylation changes in these sites. Our rule-based classifier reports combinations of CpG sites, together with changes in their methylation status in the form of easy-to-read IF-THEN rules, which allows for identification of the genes associated with the underlying sites. CONCLUSION: We utilized machine learning and statistical methods to discretize decision class (age) values to get a general pattern of methylation changes over the lifespan. The CpG sites present in the significant rules were annotated to genes involved in brain formation, general development, as well as genes linked to cancer and Alzheimer's disease. PMID- 27663461 TI - Lymph Node Dissection is Not Associated with Improved Survival among Patients Undergoing Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: A Propensity Score Based Analysis. AB - PURPOSE: The oncologic benefit of lymph node dissection for patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma is uncertain. Therefore, we evaluated the association of lymph node dissection with oncologic outcomes among patients undergoing cytoreductive nephrectomy. MATERIALS AND METHODS: We identified 305 patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma between 1990 and 2010, of whom 188 (62%) underwent lymph node dissection. Several propensity score techniques were used to evaluate cancer specific and all cause mortality. Internally predicted probabilities for pN1 disease were estimated using logistic regression. RESULTS: Overall 74 (24%) patients had pN1 disease and median followup was 8.5 years (IQR 5.6-10.7). After propensity score adjustment there were no significant differences in clinicopathological features according to whether lymph node dissection was performed. In the overall cohort lymph node dissection was not significantly associated with cancer specific or all cause mortality using any of the propensity score techniques. Moreover, lymph node dissection was not associated with survival outcomes in patients at increased risk for pN1 disease, including patients with preoperative radiographic lymphadenopathy (cN1) or across increasing probability thresholds for pN1 disease from 0.20 to 0.80. Nodal metastases were associated with more aggressive primary tumor features and significantly shorter cancer specific survival. CONCLUSIONS: Among patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma, lymph node dissection was not associated with improved oncologic outcomes in the overall cohort, for patients with preoperative radiographic lymphadenopathy or across increasing probability thresholds for pN1 disease. These findings suggest that lymph node dissection at cytoreductive nephrectomy does not confer an oncologic benefit by cytoreduction of nodal metastases. The presence of nodal metastases is associated with more aggressive tumor biology. PMID- 27663460 TI - Adherence to National Comprehensive Cancer Network(r) Guidelines for Testicular Cancer. AB - PURPOSE: Testicular cancer is the most common malignancy among young men and well established treatment guidelines exist to optimize outcomes. We characterized errors in the management of testicular cancer observed among patients seen at 3 referral centers in the United States. MATERIALS AND METHODS: We retrospectively reviewed data from 593 patients presenting with testicular cancer to 3 academic medical centers from 2007 to 2016. Nonguideline directed care was defined as management differing from National Comprehensive Care Network guideline recommendations. Cases of nonguideline directed care were systematically described. Patient and tumor characteristics were compared between guideline directed care and nonguideline directed care. Multivariable logistic regression was used to identify predictors of nonguideline directed care, and Cox regression modeling was used to assess the association between nonguideline directed care and relapse-free survival. RESULTS: Nonguideline directed care was identified in 177 of 593 (30%) patients. Inappropriate imaging (44%) and overtreatment (40%) were the most common classifications. Misdiagnosis (24%) and under treatment (16%) occurred relatively frequently, while inappropriate treatment (6%) was rare. Multivariable Cox regression modeling controlling for race, tumor stage and tumor histology identified nonguideline directed care as a significant predictor of relapse (HR 2.49, 95% CI 1.61-3.85, p <0.01). CONCLUSIONS: Nonguideline directed care of patients with testicular cancer is common, most frequently in the form of inappropriate imaging and overtreatment. Nonguideline directed care leads to delayed definitive therapy, unnecessary morbidity and higher rates of relapse. PMID- 27663459 TI - Variation in Guideline Concordant Active Surveillance Followup in Diverse Urology Practices. AB - PURPOSE: We examined the frequency of followup prostate specific antigen testing and prostate biopsy among men treated with active surveillance in the academic and community urology practices comprising MUSIC (Michigan Urological Surgery Improvement Collaborative). MATERIALS AND METHODS: MUSIC is a consortium of 42 practices that maintains a prospective clinical registry with validated clinical data on all patients diagnosed with prostate cancer at participating sites. We identified all patients in MUSIC practices who entered active surveillance and had at least 2 years of continuous followup. After determining the frequency of repeat prostate specific antigen testing and prostate biopsy, we calculated rates of concordance with NCCN Guidelines(r) recommendations (ie at least 3 prostate specific antigen tests and 1 surveillance biopsy) collaborative-wide and across individual practices. RESULTS: We identified 513 patients who entered active surveillance from January 2012 through September 2013 and had at least 2 years of followup. Among the 431 men (84%) who remained on active surveillance for 2 years 132 (30.6%) underwent followup surveillance testing at a frequency that was concordant with NCCN(r) (National Comprehensive Cancer Network(r)) recommendations. At the practice level, the median rate of guideline concordant followup was 26.5% (range 10% to 67.5%, p <0.001). Among patients with discordant followup, the absence of followup biopsy was common and not significantly different across practices (median rate 82.0%, p = 0.35). CONCLUSIONS: Among diverse community and academic practices in Michigan, there is wide variation in the proportion of men on active surveillance who meet guideline recommendations for followup prostate specific antigen testing and repeat biopsy. These data highlight the need for standardized active surveillance pathways that emphasize the role of repeat surveillance biopsies. PMID- 27663462 TI - Moral Values Congruence and Miners' Policy Following Behavior: The Role of Supervisor Morality. AB - Ethical culture construction is beneficial to maximize policy following behavior (PFB) and avoid accidents of coal miners in an economic downturn. This paper examines the congruence between coal mine ethical culture values (ECVs) and miners' moral values (MVs) and the relationship with PFB. To shed light on this relationship, supervisor moral values (SMVs) act as a key moderator. We build on the initial structure of values to measure ECVs, MVs, and SMVs. At the same time, available congruence was defined to describe the relationship between the two values. Drawing upon a survey of 267 miners in Chinese large state-owned coal mining enterprises, results revealed that ECVs-MVs congruence had a linear relationship with intrinsic PFB (IPFB) and a non-linear relationship with extrinsic PFB. These findings demonstrate that SMVs had a moderating effect on the relationship between ECVs-MVs congruence and extrinsic PFB. Thus, we continued to calculate the available congruence scope in tested enterprises. Furthermore, this study gives relative management proposals and suggestions to improve miners' moral standards and to reduce coal mine accidents. PMID- 27663463 TI - Patients With a History of Idiopathic Deep Venous Thrombosis Have Long-Term Increased Levels of Inflammatory Markers and Markers of Endothelial Damage. AB - INTRODUCTION: Although the role of inflammation in DVT has been investigated in different studies, there is no definite answer as to whether increased systemic inflammation is the cause or the consequence of DVT. AIM: To follow inflammatory parameters in a cohort of patients with idiopathic DVT. METHODS: Out of 49 patients with an acute idiopathic DVT, which were investigated four months after an acute episode (DEVTA 1), 43 patients were included in the follow-up study investigating inflammatory markers and hemostatic markers of endothelial damage five years after an acute DVT (DEVTA 2). A control group consisted of 43 sex and age matched healthy subjects (CONTROLS). RESULTS: The levels of inflammatory markers were significantly higher in DEVTA 2 in comparison to CONTROLS: tumor necrosis factor alpha 2.0 pg/mL (1.1-2.3) vs 1.3 pg/mL (0.8-1.9), p < .001, high sensitivity C-reactive protein 3.2 mg/L (1.5-5.2) vs 1.7 mg/L (0.9-3.0), p = .008, interleukin-6 (IL-6) 2.7 pg/mL (2.0-3.5) vs 2.1 pg/mL (1.5-2.6), p = .025, IL-8 5.0 pg/mL (3.6-7.3) vs 2.4 pg/mL (1.8-2.8), p < .001. IL-10 was significantly decreased (0.9 pg/mL (0.7-1.8) vs 1.8 (1.5-2.2), p < .001. Most of the proinflammatory markers remained elevated in the DEVTA 2 in comparison to DEVTA 1. Markers of endothelial damage were higher in DEVTA 2 in comparison to CONTROLS and higher than in DEVTA 1. CONCLUSION: Patients with idiopathic DVT have long-term increased inflammatory markers and markers of endothelial damage. These findings favor the hypothesis that inflammation is a cause and not merely a consequence of acute DVT. PMID- 27663465 TI - Eikenella corrodens bone and hip joint infection. A case report and literature review. AB - : Eikenella corrodens (EC) is a human commensal microorganism of the mouth flora. This bacterium is rarely reported in bone and joint infections in children, but the consequences on the joint function can be devastating and irreversible. We report the case of septic arthritis of the hip following an oral wound in a 12 year-old boy. The progression of the condition was favorable with no complications or pain observed after antibiotic treatment. Clinical and radiological examinations showed a satisfactory outcome at 6 months with no sign of recurrence or complication (growth disorder). Children's osteomyelitis and arthritis caused by EC have been mostly reported after human bites or extremity pricks. This slow-growing organism is rarely diagnosed but should be considered as a potential pathogenetic agent and treated aggressively, especially since the antibiotic therapy is simple and achieves good results. LEVEL OF EVIDENCE: Level IV. PMID- 27663464 TI - [Childhood postinfectious erythema multiforme]. AB - Postinfectious erythema multiforme is an uncommon skin disease in childhood that can have a strong impact, especially in infants if there is involvement of the mucous membranes. The lesion is targeted (central bullous lesions with three concentric circles). Its diagnosis is typically made clinically. Atypical forms are the highly inflammatory, mainly bullous type, with exclusive involvement of the mucous membrane, or recurrent erythema multiforme. The diagnosis of erythema multiforme is frequently suspected in children with urticaria multiforme. Kawasaki disease and toxic epidermal necrolysis may have a target-like skin aspect with mucosal involvement, and should be considered when planning treatment. The two major infectious etiologies in children are Mycoplasma pneumoniae and Herpes simplex. More recently, postvaccination erythema multiforme has been reported with the majority of vaccines used in pediatric practice. The prognosis is usually good but requires observation of the mucosal involvement because of the risk of serious complications. The treatment of erythema multiforme is essentially symptomatic, with etiology-related treatment. PMID- 27663466 TI - Blastomycosis infection in an adolescent patient with Hodgkin lymphoma. PMID- 27663467 TI - Expressed var gene repertoire and variant surface antigen diversity in a shrinking Plasmodium falciparum population. AB - The var gene-encoded erythrocyte membrane protein-1 of Plasmodium falciparum (PfEMP-1) is the main variant surface antigen (VSA) expressed on infected erythrocytes. The rate at which antibody responses to VSA expressed by circulating parasites are acquired depends on the size of the local VSA repertoire and the frequency of exposure to new VSA. Because parasites from areas with declining malaria endemicity, such as the Amazon, typically express a restricted PfEMP-1 repertoire, we hypothesized that Amazonians would rapidly acquire antibodies to most locally circulating VSA. Consistent with our expectations, the analysis of 5878 sequence tags expressed by 10 local P. falciparum samples revealed little PfEMP-1 DBL1alpha domain diversity. Among the most commonly expressed DBL1alpha types, 45% were shared by two or more independent parasite lines. Nevertheless, Amazonians displayed major gaps in their repertoire of anti-VSA antibodies, although the breadth of anti-VSA antibody responses correlated positively with their cumulative exposure to malaria. We found little antibody cross-reactivity even when testing VSA from related parasites expressing the same dominant DBL1alpha types. We conclude that variant-specific immunity to P. falciparum VSAs develops slowly despite the relatively restricted PfEMP-1 repertoire found in low-endemicity settings. PMID- 27663468 TI - Identification and typing of free-living Acanthamoeba spp. by MALDI-TOF MS Biotyper. AB - Over the years, the potential pathogenicity of Acanthamoeba for humans and animals has gained increasing attention from the scientific community. More than 24 species belong to this genus, however only some of them are causative agents of keratitis and encephalitis in humans. Due to technical difficulties in diagnosis, these infections are likely to be under-detected. The introduction of 18S rDNA amplification for the identification of Acanthamoeba has dramatically enhanced diagnosis performances, but the attestation of genotyping requires supplementary sequencing-based procedures. In this study, 15 Acanthamoeba strains were collected and grown on nutrient agar media. Each strain was genotyped by end point PCR assay for the amplification of the 18S rDNA gene and the genotype was assigned by sequencing analysis through neighbor joining phylogenetic tree. In order to optimize standardization of the MALDI-TOF MS assay, we established the collection time point at the cystic phase. Two strains of each genotype were randomly chosen to customize the biotyper database. For all strains, 24 spectral measurements were acquired and submitted to identification and cluster analysis of spectra. The obtained results highlighted the correct identification of Acanthamoeba strains and the overlapping of spectra dendrogram clusters to the 18S genotype assignations. In conclusion, the MALDI-TOF MS Biotyper revealed the capability to identify and genotype the Acanthamoeba strains, providing a new frontier in the diagnostic identification of amaebae and in taxonomic and phylogenetic studies. PMID- 27663469 TI - Synergistic effect of rSAG1 and rGRA2 antigens formulated in PLGA microspheres in eliciting immune protection against Toxoplasama gondii. AB - There is still no human vaccine against Toxoplasma gondii (T. gondii), as one of the most successful parasites. In present study, we designed a subunit vaccine composed of recombinant SAG1 (rSAG1) and recombinant GRA2 (rGRA2) proteins. In order to improve the induced immune responses, rSAG1 and rGRA2 were adsorbed on Poly (DL-lactide-co-glycolide) (PLGA) microspheres (MS) prepared by double emulsion solvent evaporation method. BALB/c mice were subcutaneously vaccinated by rSAG1-adsorbed PLGA MS (rSAG1-PLGA), rGRA2-adsorbed PLGA MS (rGRA2-PLGA), and the mixture of both formulations (rSAG1/rGRA2-PLGA), twice with a 3-week interval. PLGA MS characteristics, protein release, cellular and humoral immune responses, and protection against acute toxoplasmosis were evaluated. All vaccinated mice induced significantly partial protection and longer survival times associated with higher IFN-gamma/IL-10 ratio and higher amount of Toxoplasma-specific IgG antibodies compared to control groups. Interestingly, the synergistic effect of rSAG1 and rGRA2 in eliciting more potent cellular and humoral responses and consequently higher protection in comparison to single antigen was confirmed. This study introduces the mixture of rSAG1 and rGRA2 (derived from different stages of Toxoplasma life-cycle) formulated in PLGA MS as a promising candidate in vaccine development against T. gondii. PMID- 27663470 TI - A Case-Control Study: Infectious Burden Increased the Occurrence of Vascular Cognitive Impairment No Dementia. PMID- 27663472 TI - Dramatic acceleration of reproductive aging, contraction of biochemical fecundity and healthspan-lifespan implications of opioid-induced endocrinopathy-FSH/LH ratio and other interrelationships. AB - Whilst disturbances of female reproductive hormones and function are commonplace in opioid dependence, their pathophysiological interrelationships are not well understood. Hormonal levels in females were compared in 77 opioid dependent patients (ODP) and 148 medical controls (MC) including 205 and 364 repeat studies. Significant changes in FSH, LH, oestradiol, testosterone and SBG were noted including power functions with age. The FSH/LH was lower in ODP (P=0.0150) and the ratio inversion point occurred at 28.06+/-9.36v. 46.26+/-4.76years, implying a 58% reduction in fertility duration. FSH has been shown to induce ovarian failure and GnRH (controlling LH and FSH) has been shown to regulate longevity systemically. This implies that, far from being benign, these findings explicate the adverse experience of female compared to male ODP, exacerbate opioid-dependent aging amongst females, and informs the care of opioid dependent women, particularly relating to the choice, dose and duration of agonist or antagonist therapy. PMID- 27663473 TI - Observation-based metrics for residential dampness and mold with dose-response relationships to health: A review. AB - An important proportion of respiratory illness is considered attributable to residential dampness or mold (D/M). Developing health-protective D/M guidelines has been challenging, in part because unhealthy levels of indoor D/M cannot be defined using available microbiological measurements. This review paper explores reported multilevel, observation-based (eg visual or olfactory) D/M metrics for potential in defining unhealthy levels of residential D/M. For many of the 33 multilevel residential D/M metrics identified, health risks generally increased as observed D/M increased. Although some metrics seemed too complex for practical use, simple metrics had among the strongest associations with health outcomes. Available findings suggest the feasibility of setting observation-based D/M thresholds to trigger remedial action, using further improved D/M metrics without microbiological measurements (at least until the actual dampness-related agents that cause illness are better quantified). Additional data would allow setting health-protective D/M thresholds more precisely. Also, metrics could better reflect hidden D/M by more strongly emphasizing mold odor, which has demonstrated strong associations with health effects. PMID- 27663471 TI - Zinc deficiency reduces fertility in C. elegans hermaphrodites and disrupts oogenesis and meiotic progression. AB - Zinc is necessary for successful gametogenesis in mammals; however the role of zinc in the gonad function of non-mammalian species has not been investigated. The genetic tractability, short generation time, and hermaphroditic reproduction of the nematode C. elegans offer distinct advantages for the study of impaired gametogenesis as a result of zinc deficiency. However the phenotypic reproductive effects arising from zinc restriction have not been established in this model. We therefore examined the effect of zinc deficiency on C. elegans reproduction by exposing worms to the zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethane 1,2-diamine (TPEN). Treatment began at the early larval stage and continued until reproductive senescence. TPEN treatment reduced the total number of progeny produced by C. elegans hermaphrodites compared with control subjects, with the largest difference in output observed 48h after larval stage 4. At this time point, zinc deficient worms displayed fewer embryos in the uterus and disorganized oocyte development when observed under DIC microscopy. DAPI staining revealed impaired oogenesis and chromosome dynamics with an expanded region of pachytene stage oocytes extending into the proximal arm of the gonad. This phenotype was not seen in control or zinc-rescue subjects. This study demonstrates that reproduction in C. elegans is sensitive to environmental perturbations in zinc, indicating that this is a good model for future studies in zinc-mediated subfertility. Aberrant oocyte development and disruption of the pachytene-diplotene transition indicate that oogenesis in particular is affected by zinc deficiency in this model. PMID- 27663474 TI - Theory and practice of clinical pharmacodynamics in oncology drug development. AB - The clinical development of molecularly targeted cancer therapies is enhanced by proof of mechanism of action as well as proof of concept, which relate molecular pharmacodynamics to efficacy via changes in cancer cell biology and physiology resulting from drug action on its intended target. Here, we present an introduction to the field of clinical pharmacodynamics, its medical and laboratory aspects, and its practical incorporation into clinical trials. We also describe key success factors that are useful for judging the quality of clinical pharmacodynamic studies, including biopsy quality and suitability, specimen handling, assay fitness-for-purpose, and reagent quality control. This introduction provides not only context for the following articles in this issue, but also an appreciation of the role of well-conducted clinical pharmacodynamic studies in oncology drug development. PMID- 27663476 TI - Establishing proof of mechanism: Assessing target modulation in early-phase clinical trials. AB - Since modulation of the putative target and the observed anti-tumor effects form the basis for the clinical development of a molecularly targeted therapy, early phase clinical trials should be designed to demonstrate proof-of-mechanism in tissues of interest. In addition to establishing safety and the maximum tolerated dose, first-in-human clinical trials should be designed to demonstrate target modulation, define the proposed mechanism of action, and evaluate pharmacokinetic pharmacodynamic relationships of a new anti-cancer agent. Assessing target modulation in paired tumor biopsies in patients with solid tumors presents multiple challenges, including procedural issues such as patient safety, ethical considerations, and logistics of sample handling and processing. In addition, the availability of qualified biomarker assay technologies, resources to conduct such studies, and real-time analysis of samples to detect inter-species differences that may affect the determination of optimal sampling time points must be taken into account. This article provides a discussion of the challenges that confront the practical application of pharmacodynamic studies in early-phase clinical trials of anti-cancer agents. PMID- 27663475 TI - Critical parameters in targeted drug development: the pharmacological audit trail. AB - The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) establishing pharmacokinetic characteristics; (3) providing evidence of target engagement, pathway modulation, and biological effect with proof of concept pharmacodynamic biomarkers; (4) determining intermediate biomarkers of response; (5) assessing tumor response; and (6) determining how to overcome resistance by combination or sequential therapy and new target/drug discovery. The questions asked in the PhAT should be viewed as a continuum and not used in isolation. Different drug development programmes derive different types of benefit from these questions. The PhAT is critical in making go-no-go decisions in the development of currently studied drugs and will continue to be relevant to discovery and development of future generations of anticancer agents. PMID- 27663477 TI - Translating pharmacodynamic biomarkers from bench to bedside: analytical validation and fit-for-purpose studies to qualify multiplex immunofluorescent assays for use on clinical core biopsy specimens. AB - Multiplex pharmacodynamic (PD) assays have the potential to increase sensitivity of biomarker-based reporting for new targeted agents, as well as revealing significantly more information about target and pathway activation than single biomarker PD assays. Stringent methodology is required to ensure reliable and reproducible results. Common to all PD assays is the importance of reagent validation, assay and instrument calibration, and the determination of suitable response calibrators; however, multiplex assays, particularly those performed on paraffin specimens from tissue blocks, bring format-specific challenges adding a layer of complexity to assay development. We discuss existing multiplex approaches and the development of a multiplex immunofluorescence assay measuring DNA damage and DNA repair enzymes in response to anti-cancer therapeutics and describe how our novel method addresses known issues. PMID- 27663478 TI - Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells. AB - Circulating tumor cells (CTCs), which are captured from blood with anti epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints. We discuss the use of CellSearch (Janssen Diagnostics, LLC, Raritan, NJ) CTC isolation technology for monitoring PD response in early phase trials. We present representative data from three clinical trials with the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) suggesting that CTCs can be used to measure PD effects. However, while often leading to hypothesis-generating information, our experience points to the difficulty in obtaining sufficient EpCAM-expressing CTCs from patients with advanced disease to reach statistically significant conclusions about PD effects from each trial. Overall, the level of phenotypic heterogeneity observed in specimens from patients with advanced carcinomas suggests caution in the use of cell-surface differentiation marker-based methods for isolating CTCs. PMID- 27663480 TI - The root causes of pharmacodynamic assay failure. AB - Robust pharmacodynamic assay results are valuable for informing go/no-go decisions about continued development of new anti-cancer agents and for identifying combinations of targeted agents, but often pharmacodynamic results are too incomplete or variable to fulfill this role. Our experience suggests that variable reagent and specimen quality are two major contributors to this problem. Minimizing all potential sources of variability in procedures for specimen collection, processing, and assay measurements is essential for meaningful comparison of pharmacodynamic biomarkers across sample time points. This is especially true in the evaluation of pre- and post-dose tumor biopsies, which suffer from high levels of tumor insufficiency due to variations in biopsy collection techniques and significant specimen heterogeneity within and across patients. Developing methods to assess heterogeneous biopsies is necessary in order to evaluate a majority of tumor biopsies collected for pharmacodynamic biomarker studies. Improved collection devices and standardization of methods are being sought in order to improve the tumor content and quality of tumor biopsies. In terms of reagent variability, we have found that stringent initial reagent qualification and quality control of R&D-grade reagents is critical to minimize lot-to-lot variability and prevent assay failures, especially for clinical pharmacodynamic questions, which often demand assay performance that meets or exceeds clinical diagnostic assay standards. Rigorous reagent specifications and use of appropriate assay quality control methodologies help to ensure consistency between assay runs, laboratories and trials to provide much needed pharmacodynamic insights into the activity of investigational agents. PMID- 27663479 TI - Using reverse-phase protein arrays as pharmacodynamic assays for functional proteomics, biomarker discovery, and drug development in cancer. AB - The majority of the targeted therapeutic agents in clinical use target proteins and protein function. Although DNA and RNA analyses have been used extensively to identify novel targets and patients likely to benefit from targeted therapies, these are indirect measures of the levels and functions of most therapeutic targets. More importantly, DNA and RNA analysis is ill-suited for determining the pharmacodynamic effects of target inhibition. Assessing changes in protein levels and function is the most efficient way to evaluate the mechanisms underlying sensitivity and resistance to targeted agents. Understanding these mechanisms is necessary to identify patients likely to benefit from treatment and to develop rational drug combinations to prevent or bypass therapeutic resistance. There is an urgent need for a robust approach to assess protein levels and protein function in model systems and across patient samples. While "shot gun" mass spectrometry can provide in-depth analysis of proteins across a limited number of samples, and emerging approaches such as multiple reaction monitoring have the potential to analyze candidate markers, mass spectrometry has not entered into general use because of the high cost, requirement of extensive analysis and support, and relatively large amount of material needed for analysis. Rather, antibody-based technologies, including immunohistochemistry, radioimmunoassays, enzyme-linked immunosorbent assays (ELISAs), and more recently protein arrays, remain the most common approaches for multiplexed protein analysis. Reverse-phase protein array (RPPA) technology has emerged as a robust, sensitive, cost effective approach to the analysis of large numbers of samples for quantitative assessment of key members of functional pathways that are affected by tumor targeting therapeutics. The RPPA platform is a powerful approach for identifying and validating targets, classifying tumor subsets, assessing pharmacodynamics, and identifying prognostic and predictive markers, adaptive responses and rational drug combinations in model systems and patient samples. Its greatest utility has been realized through integration with other analytic platforms such as DNA sequencing, transcriptional profiling, epigenomics, mass spectrometry, and metabolomics. The power of the technology is becoming apparent through its use in pathology laboratories and integration into trial design and implementation. PMID- 27663481 TI - Pharmacodynamic analyses in a multi-laboratory network: lessons from the poly(ADP ribose) assay. AB - Clinical pharmacodynamic assays need to meet higher criteria for sensitivity, precision, robustness, and reproducibility than those expected for research-grade assays because of the long duration of clinical trials and the potentially unpredictable number of laboratories running the assays. This report describes the process of making an immunoassay based on commercially available reagents "clinically ready". The assay was developed to quantify poly(ADP-ribose) (PAR) levels as a marker of PAR polymerase inhibitor activity for a proof-of-concept phase 0 clinical trial at the National Cancer Institute (NCI) and subsequent clinical trials. In this publication, we retrospectively examine the measures taken to validate the published PAR immunoassay and outline key lessons learned during the development and implementation of these procedures at both internal and external clinical trial sites; these measures included optimizing PAR measurements in tumor biopsies and peripheral blood mononuclear cells (PBMCs), reagent qualification, analytical validation and assay quality control, instrument qualification and method quality control, and support for external laboratories. PMID- 27663482 TI - Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations. AB - Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell-tumor cell proximity). Evaluating such "trans-cellular pharmacology," in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell's biological role. We have termed this form of nearest neighbor image analysis of drug action "proximity PD microscopy," to indicate the importance of the location of the PD-biomarker response within the cellular landscape of a tumor specimen. We discuss herein the major modes of immunotherapy, and lay out a blueprint for using PD assessment to optimize dosage regimens of single agents and guide development of combination immunotherapy regimens, using PD1/PD-L1 immune checkpoint inhibition as a case study. PMID- 27663484 TI - Functional crosstalk between WNT signaling and tyrosine kinase signaling in cancer: Seminars in Oncology, Vol 42, No 6, December 2015, pp 820-831. PMID- 27663485 TI - Psychiatrist who was cleared by first tribunal is struck off. PMID- 27663483 TI - Pharmacodynamic endpoints as clinical trial objectives to answer important questions in oncology drug development. AB - Analyzing the molecular interplay between malignancies and therapeutic agents is rarely a straightforward process, but we hope that this special issue of Seminars has highlighted the clinical value of such endeavors as well as the relevant theoretical and practical considerations. Here, we conclude with both an overview of the various high-value applications of clinical pharmacodynamics (PD) in developmental therapeutics and an outline of the framework for incorporating PD analyses into the design of clinical trials. Given the increasingly recognized importance of determining and administering the biologically effective dose (BED) and schedule of targeted agents, we explain how clinical PD biomarkers specific to the agent mechanism of action (MOA) can be used for the development of pharmacodynamics-guided biologically effective dosage regimens (PD-BEDR) to maximize the efficacy and minimize the toxicity of targeted therapies. In addition, we discuss how MOA-based PD biomarker analyses can be used both as patient selection diagnostic tools and for designing novel drug combinations targeting the specific mutational signature of a given malignancy. We also describe the role of PD analyses in clinical trials, including for MOA confirmation and dosage regimen optimization during phase 0 trials as well as for correlating molecular changes with clinical efficacy when establishing proof-of concept in phase I/II trials. Finally, we outline the critical technological developments that are needed to enhance the quality and quantity of future clinical PD data collection, broaden the types of molecular questions that can be answered in the clinic, and, ultimately, improve patient outcomes. PMID- 27663486 TI - The use of pain relief during labor among migrant obstetric populations. AB - OBJECTIVE: To identify patterns in intrapartum analgesia use in the migrant obstetric population. METHODS: A retrospective analysis included all deliveries with neonates above 500g in weight at a university hospital in Dublin, Ireland between 2009 and 2013. Analgesia was classified as neuraxial or non-neuraxial. Parturients were excluded owing to missing data, elective cesarean deliveries, and the use of analgesia during treatment for obstetric complications. RESULTS: There were 36 689 deliveries included in the present study. Increased odds of not using neuraxial analgesia during delivery were observed among migrant parturients from North Africa, Sub-Saharan Africa, the Far East, India, and Eastern Europe compared with western Europe (all P<0.05). Increased odds of not receiving any analgesia during delivery were demonstrated among parturients from North Africa, Sub-Saharan Africa, the Far East, North America, Eastern Europe, and India compared with western Europe (all P<0.05). CONCLUSIONS: Disparities exist in the use of intrapartum analgesia between migrant and western European populations in Ireland. Migrants from Africa were the least likely to use any analgesia. The reasons for this are speculative but could be influenced by expectations of care in the region of origin. PMID- 27663487 TI - In vitro complement activation, adherence to red blood cells and induction of mononuclear cell cytokine production by four strains of Aggregatibacter actinomycetemcomitans with different fimbriation and expression of leukotoxin. AB - BACKGROUND AND OBJECTIVE: The periodontal pathogen Aggregatibacter actinomycetemcomitans has been proposed as pro-atherogenic, and complement mediated adherence to red blood cells (RBCs) may facilitate its systemic spread. We investigated the ability of four strains of A. actinomycetemcomitans with differential expression of leukotoxin A (LtxA) and fimbriae to activate complement, adhere to RBCs and elicit cytokine responses by mononuclear cells (MNCs). MATERIAL AND METHODS: Aggregatibacter actinomycetemcomitans serotype b strains HK 921, HK 1651, HK 2092 and HK 2108 were fluorescence-labeled, incubated with human whole blood cells in the presence of autologous serum, and assessed for RBC adherence by flow cytometry and for capacity to induce cytokine production by cytometric bead array analysis. The levels of IgG to A. actinomycetemcomitans serotype b were quantified by ELISA, as was consumption of complement. RESULTS: The JP2 clone variants HK 1651 and, to a lesser extent, HK 2092, consumed complement efficiently, while HK 2108 (= strain Y4) consumed complement poorly. Nonetheless, the four tested strains adhered equally well to RBCs in the presence of autologous serum, without causing RBC lysis. The JP2 clone variant HK 2092, selectively lacking LtxA production, induced higher production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 by MNCs than did the other three strains, while the four strains induced similar production of IL-12p70. RBCs facilitated the HK 2092-induced production of TNF-alpha and IL-1beta, and IL-6 was enhanced by RBCs, and this facilitation could be counteracted by blockade of complement receptor 3 (CD11b/CD18). CONCLUSION: Our data suggest that the JP2 clone of A. actinomycetemcomitans, most closely resembled by the variant HK 1651, activates complement well, while strain Y4, represented by HK 2108, activates complement poorly. However, all strains of A. actinomycetemcomitans adhere to RBCs and, when capable of producing LtxA, prevent production of inflammatory cytokines by MNCs. This "immunologically silent" immune adherence may facilitate systemic spread and atherogenesis. PMID- 27663489 TI - The Value of Neonatal Neurocritical Care. PMID- 27663490 TI - A Cerebral Infarction in a Girl With Sturge-Weber Syndrome. PMID- 27663491 TI - Clinical spectrum of yellow phosphorous poisoning in a tertiary care centre in South India: a case series. AB - Rodenticides such as yellow phosphorus are highly toxic compounds which are commonly used for pest control. Reports of yellow phosphorus poisoning from tropical nations is scanty. In this retrospective study, we report the clinical features, mortality and predictors of mortality among nine patients at a tertiary care centre in south India. Yellow phosphorus consumption was common among a younger age group of patients. The mean duration of presentation after consumption was five days. The most common clinical manifestations seen were abdominal pain and vomiting followed by a depressed sensorium. Features of acute liver failure including coagulopathy were seen in all patients. Despite all patients receiving supportive therapy, a poor outcome or death resulted in the majority. Early referral to a tertiary care centre, meticulous monitoring and supportive measures are key elements of patient management as there are no specific antidotes available at present. Increase in public and physician awareness to the toxin and implementation of preventive policies is of utmost importance. PMID- 27663492 TI - MELAS syndrome presenting with seizure and deafness in a Malawian boy. PMID- 27663488 TI - Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke. AB - BACKGROUND: Malignant middle cerebral artery infarct syndrome is a potentially fatal complication of stroke that is poorly understood in children. We studied the frequency, associated characteristics, and outcomes of this condition in children. METHODS: Children, aged two months to 18 years with acute middle cerebral artery infarct diagnosed at our center between January 2005 and December 2012 were studied. Associations with malignant middle cerebral artery infarct syndrome were sought, including age, seizures, neurological deficit severity (Pediatric National Institute of Health Stroke Severity Score), stroke etiology, fever, blood pressure, blood glucose, infarct location, infarct volume (modified pediatric Alberta Stroke Program Early Computed Tomography Score), and arterial occlusion. Death and neurological outcomes were determined. RESULTS: Among 66 children with middle cerebral artery stroke, 12 (18%) developed malignant middle cerebral artery infarct syndrome, fatal in three. Prolonged seizures during the first 24 hours (odds ratio, 25.51; 95% confidence interval, 3.10 to 334.81; P = 0.005) and a higher Pediatric National Institute of Health Stroke Severity Score (odds ratio, 1.22; 95% confidence interval, 1.08 to 1.45; P = 0.006) were independently associated with malignant middle cerebral artery infarct syndrome. All children aged greater than two years with a Pediatric National Institute of Health Stroke Severity Score >=8 and initial seizures >=5 minutes duration developed malignant middle cerebral artery infarct syndrome (100%). CONCLUSIONS: Malignant middle cerebral artery infarct syndrome affects nearly one in five children with acute middle cerebral artery stroke. Children with higher Pediatric National Institute of Health Stroke Severity Scores and prolonged initial seizures are at greatly increased risk for malignant middle cerebral artery infarct syndrome. Children with middle cerebral artery infarcts warrant intensive neuroprotective management and close monitoring to enable early referral for hemicraniectomy surgery. PMID- 27663493 TI - Biospark: scalable analysis of large numerical datasets from biological simulations and experiments using Hadoop and Spark. AB - : Data-parallel programming techniques can dramatically decrease the time needed to analyze large datasets. While these methods have provided significant improvements for sequencing-based analyses, other areas of biological informatics have not yet adopted them. Here, we introduce Biospark, a new framework for performing data-parallel analysis on large numerical datasets. Biospark builds upon the open source Hadoop and Spark projects, bringing domain-specific features for biology. AVAILABILITY AND IMPLEMENTATION: Source code is licensed under the Apache 2.0 open source license and is available at the project website: https://www.assembla.com/spaces/roberts-lab-public/wiki/Biospark CONTACT: eroberts@jhu.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663495 TI - An accessibility-incorporated method for accurate prediction of RNA-RNA interactions from sequence data. AB - MOTIVATION: RNA-RNA interactions via base pairing play a vital role in the post transcriptional regulation of gene expression. Efficient identification of targets for such regulatory RNAs needs not only discriminative power for positive and negative RNA-RNA interacting sequence data but also accurate prediction of interaction sites from positive data. Recently, a few studies have incorporated interaction site accessibility into their prediction methods, indicating the enhancement of predictive performance on limited positive data. RESULTS: Here we show the efficacy of our accessibility-based prediction model RactIPAce on newly compiled datasets. The first experiment in interaction site prediction shows that RactIPAce achieves the best predictive performance on the newly compiled dataset of experimentally verified interactions in the literature as compared with the state-of-the-art methods. In addition, the second experiment in discrimination between positive and negative interacting pairs reveals that the combination of accessibility-based methods including our approach can be effective to discern real interacting RNAs. Taking these into account, our prediction model can be effective to predict interaction sites after screening for real interacting RNAs, which will boost the functional analysis of regulatory RNAs. AVAILABILITY AND IMPLEMENTATION: The program RactIPAce along with data used in this work is available at https://github.com/satoken/ractip/releases/tag/v1.0.1 CONTACT: : ykato@rna.med.osaka-u.ac.jp or shingo@i.kyoto-u.ac.jpSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663494 TI - A generative model for the behavior of RNA polymerase. AB - MOTIVATION: Transcription by RNA polymerase is a highly dynamic process involving multiple distinct points of regulation. Nascent transcription assays are a relatively new set of high throughput techniques that measure the location of actively engaged RNA polymerase genome wide. Hence, nascent transcription is a rich source of information on the regulation of RNA polymerase activity. To fully dissect this data requires the development of stochastic models that can both deconvolve the stages of polymerase activity and identify significant changes in activity between experiments. RESULTS: We present a generative, probabilistic model of RNA polymerase that fully describes loading, initiation, elongation and termination. We fit this model genome wide and profile the enzymatic activity of RNA polymerase across various loci and following experimental perturbation. We observe striking correlation of predicted loading events and regulatory chromatin marks. We provide principled statistics that compute probabilities reminiscent of traveler's and divergent ratios. We finish with a systematic comparison of RNA Polymerase activity at promoter versus non-promoter associated loci. AVAILABILITY AND IMPLEMENTATION: Transcription Fit (Tfit) is a freely available, open source software package written in C/C ++ that requires GNU compilers 4.7.3 or greater. Tfit is available from GitHub (https://github.com/azofeifa/Tfit). CONTACT: robin.dowell@colorado.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663496 TI - FBB: a fast Bayesian-bound tool to calibrate RNA-seq aligners. AB - MOTIVATION: Despite RNA-seq reads provide quality scores that represent the probability of calling a correct base, these values are not probabilistically integrated in most alignment algorithms. Based on the quality scores of the reads, we propose to calculate a lower bound of the probability of alignment of any fast alignment algorithm that generates SAM files. This bound is called Fast Bayesian Bound (FBB) and serves as a canonical reference to compare alignment results across different algorithms. This Bayesian Bound intends to provide additional support to the current state-of-the-art aligners, not to replace them. RESULTS: We propose a feasible Bayesian bound that uses quality scores of the reads to align them to a genome of reference. Two theorems are provided to efficiently calculate the Bayesian bound that under some conditions becomes the equality. The algorithm reads the SAM files generated by the alignment algorithms using multiple command option values. The program options are mapped into the FBB reference values, and all the aligners can be compared respect to the same accuracy values provided by the FBB. Stranded paired read RNA-seq data was used for evaluation purposes. The errors of the alignments can be calculated based on the information contained in the distance between the pairs given by Theorem 2, and the alignments to the incorrect strand. Most of the algorithms (Bowtie, Bowtie 2, SHRiMP2, Soap 2, Novoalign) provide similar results with subtle variations. AVAILABILITY AND IMPLEMENTATION: Current version of the FBB software is provided at https://bitbucket.org/irenerodriguez/fbb CONTACT: rhuerta@ucsd.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663497 TI - AcCNET (Accessory Genome Constellation Network): comparative genomics software for accessory genome analysis using bipartite networks. AB - : AcCNET (Accessory genome Constellation Network) is a Perl application that aims to compare accessory genomes of a large number of genomic units, both at qualitative and quantitative levels. Using the proteomes extracted from the analysed genomes, AcCNET creates a bipartite network compatible with standard network analysis platforms. AcCNET allows merging phylogenetic and functional information about the concerned genomes, thus improving the capability of current methods of network analysis. The AcCNET bipartite network opens a new perspective to explore the pangenome of bacterial species, focusing on the accessory genome behind the idiosyncrasy of a particular strain and/or population. AVAILABILITY AND IMPLEMENTATION: AcCNET is available under GNU General Public License version 3.0 (GPLv3) from http://sourceforge.net/projects/accnet CONTACT: : valfernandez.vf@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663498 TI - Robust classification of single-cell transcriptome data by nonnegative matrix factorization. AB - MOTIVATION: Single-cell transcriptome data provide unprecedented resolution to study heterogeneity in cell populations and present a challenge for unsupervised classification. Popular methods, like principal component analysis (PCA), often suffer from the high level of noise in the data. RESULTS: Here we adapt Nonnegative Matrix Factorization (NMF) to study the problem of identifying subpopulations in single-cell transcriptome data. In contrast to the conventional gene-centered view of NMF, identifying metagenes, we used NMF in a cell-centered direction, identifying cell subtypes ('metacells'). Using three different datasets (based on RT-qPCR and single cell RNA-seq data, respectively), we show that NMF outperforms PCA in identifying subpopulations in an accurate and robust way, without the need for prior feature selection; moreover, NMF successfully recovered the broad classes on a large dataset (thousands of single-cell transcriptomes), as identified by a computationally sophisticated method. NMF allows to identify feature genes in a direct, unbiased manner. We propose novel approaches for determining a biologically meaningful number of subpopulations based on minimizing the ambiguity of classification. In conclusion, our study shows that NMF is a robust, informative and simple method for the unsupervised learning of cell subtypes from single-cell gene expression data. AVAILABILITY AND IMPLEMENTATION: https://github.com/ccshao/nimfa CONTACTS: c.shao@Dkfz Heidelberg.de or t.hoefer@Dkfz-Heidelberg.deSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663499 TI - FastRFS: fast and accurate Robinson-Foulds Supertrees using constrained exact optimization. AB - Motivation: The estimation of phylogenetic trees is a major part of many biological dataset analyses, but maximum likelihood approaches are NP-hard and Bayesian MCMC methods do not scale well to even moderate-sized datasets. Supertree methods, which are used to construct trees from trees computed on subsets, are critically important tools for enabling the statistical estimation of phylogenies for large and potentially heterogeneous datasets. Supertree estimation is itself NP-hard, and no current supertree method has sufficient accuracy and scalability to provide good accuracy on the large datasets that supertree methods were designed for, containing thousands of species and many subset trees. Results: We present FastRFS, a new method based on a dynamic programming method we have developed to find an exact solution to the Robinson Foulds Supertree problem within a constrained search space. FastRFS has excellent accuracy in terms of criterion scores and topological accuracy of the resultant trees, substantially improving on competing methods on a large collection of biological and simulated data. In addition, FastRFS is extremely fast, finishing in minutes on even very large datasets, and in under an hour on a biological dataset with 2228 species. Availability and Implementation: FastRFS is available on github at https://github.com/pranjalv123/FastRFS. Contact: warnow@illinois.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663500 TI - FoldAtlas: a repository for genome-wide RNA structure probing data. AB - : Most RNA molecules form internal base pairs, leading to a folded secondary structure. Some of these structures have been demonstrated to be functionally significant. High-throughput RNA structure chemical probing methods generate millions of sequencing reads to provide structural constraints for RNA secondary structure prediction. At present, processed data from these experiments are difficult to access without computational expertise. Here we present FoldAtlas, a web interface for accessing raw and processed structural data across thousands of transcripts. FoldAtlas allows a researcher to easily locate, view, and retrieve probing data for a given RNA molecule. We also provide in silico and in vivo secondary structure predictions for comparison, visualized in the browser as circle plots and topology diagrams. Data currently integrated into FoldAtlas are from a new high-depth Structure-seq data analysis in Arabidopsis thaliana, released with this work. AVAILABILITY AND IMPLEMENTATION: The FoldAtlas website can be accessed at www.foldatlas.com Source code is freely available at github.com/mnori/foldatlas under the MIT license. Raw reads data are available under the NCBI SRA accession SRP066985. CONTACT: yiliang.ding@jic.ac.uk or matthew.norris@jic.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663503 TI - DDAH1-V3 transcript might act as miR-21 sponge to maintain balance of DDAH1-V1 in cultured HUVECs. AB - OBJECTIVE: To investigate whether microRNA (miRNA) miR-21 regulates dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression through binding 3' UTR region directly in human umbilical venous endothelial cells (HUVECs) and to explore whether DDAH1-V2/V3 transcripts can function as microRNA sponge, thereby modulating DDAH1-V1 expression. METHODS: The DDAH1 3'-UTR containing miR-21 recognizing sequence was cloned into PmirGLO dual-luciferase miRNA target expression plasmid to construct PmirGLO-miR-21. The plasmid and miR-21 (at concentrations of 25, 50, 100 nM, respectively) or negative control (100 nM) were co-transfected into HUVECs, luciferase activity was detected at 24 h. HUVECs were incubated with 2 MUg/ml Actinomycin D for the indicated time after miR-21 (25 nM) transfection, half-lives of DDAH1 mRNA were determined. HUVECs were transfected with PmirGLO-miR-21 alone or co-transfected with miR-21 for 24 h, DDAH1 transcripts mRNA, eNOS activity and DDAH1 protein expression were determined. RESULTS: MiR-21 decreased luciferase activity of PmirGLO-miR-21 in a dose dependent manner (P < 0.05 for 25 nM miR-21, P < 0.01 for 50 nM and 100 nM miR 21), and miR-21 inhibitor increased reporter activity of PmirGLO-miR-21 and mRNA expression of all three DDAH1 transcript variants significantly (P < 0.05, respectively). The degree of increase in endogenous DDAH1 mRNA expression by miR 21 inhibitor was more obvious for DDAH1-V3. Overexpression of miR-21 decreased mRNA expression and mRNA half-life time of all DDAH1 transcripts significantly (P < 0.05), and DDAH1-V2 displayed significantly decreased half-life time than DDAH1 V1 and -V3 with or without miR-21 transfection (P < 0.05, respectively). MiR-21 (100 nM) decreased DDAH1 protein expression and eNOS activity significantly (P < 0.05), which was reversed by PmirGLO-miR-21 transfection (P < 0.05). Transfection of PmirGLO-miR-21 alone increased intracellular miR-21 expression by approximately 5.6-fold, but only showed a trend of increase in DDAH1 protein expression. CONCLUSION: Our results confirmed DDAH1 3'-UTR as a target for miR 21, and endogenous miR-21 showed increased inhibitory effect on DDAH1-V3 transcript. DDAH1 3'-UTR, especially for DDAH1-V3, may function as miR-21 sponge to regulate DDAH1 protein expression. Modulation of miR-21-DDAH1 interaction may provide a new approach for tackling cardiovascular diseases. PMID- 27663502 TI - LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. AB - MOTIVATION: LD score regression is a reliable and efficient method of using genome-wide association study (GWAS) summary-level results data to estimate the SNP heritability of complex traits and diseases, partition this heritability into functional categories, and estimate the genetic correlation between different phenotypes. Because the method relies on summary level results data, LD score regression is computationally tractable even for very large sample sizes. However, publicly available GWAS summary-level data are typically stored in different databases and have different formats, making it difficult to apply LD score regression to estimate genetic correlations across many different traits simultaneously. RESULTS: In this manuscript, we describe LD Hub - a centralized database of summary-level GWAS results for 173 diseases/traits from different publicly available resources/consortia and a web interface that automates the LD score regression analysis pipeline. To demonstrate functionality and validate our software, we replicated previously reported LD score regression analyses of 49 traits/diseases using LD Hub; and estimated SNP heritability and the genetic correlation across the different phenotypes. We also present new results obtained by uploading a recent atopic dermatitis GWAS meta-analysis to examine the genetic correlation between the condition and other potentially related traits. In response to the growing availability of publicly accessible GWAS summary-level results data, our database and the accompanying web interface will ensure maximal uptake of the LD score regression methodology, provide a useful database for the public dissemination of GWAS results, and provide a method for easily screening hundreds of traits for overlapping genetic aetiologies. AVAILABILITY AND IMPLEMENTATION: The web interface and instructions for using LD Hub are available at http://ldsc.broadinstitute.org/ CONTACT: jie.zheng@bristol.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663501 TI - Improved methods for multi-trait fine mapping of pleiotropic risk loci. AB - MOTIVATION: Genome-wide association studies (GWAS) have identified thousands of regions in the genome that contain genetic variants that increase risk for complex traits and diseases. However, the variants uncovered in GWAS are typically not biologically causal, but rather, correlated to the true causal variant through linkage disequilibrium (LD). To discern the true causal variant(s), a variety of statistical fine-mapping methods have been proposed to prioritize variants for functional validation. RESULTS: In this work we introduce a new approach, fastPAINTOR, that leverages evidence across correlated traits, as well as functional annotation data, to improve fine-mapping accuracy at pleiotropic risk loci. To improve computational efficiency, we describe an new importance sampling scheme to perform model inference. First, we demonstrate in simulations that by leveraging functional annotation data, fastPAINTOR increases fine-mapping resolution relative to existing methods. Next, we show that jointly modeling pleiotropic risk regions improves fine-mapping resolution compared to standard single trait and pleiotropic fine mapping strategies. We report a reduction in the number of SNPs required for follow-up in order to capture 90% of the causal variants from 23 SNPs per locus using a single trait to 12 SNPs when fine-mapping two traits simultaneously. Finally, we analyze summary association data from a large-scale GWAS of lipids and show that these improvements are largely sustained in real data. AVAILABILITY AND IMPLEMENTATION: The fastPAINTOR framework is implemented in the PAINTOR v3.0 package which is publicly available to the research community http://bogdan.bioinformatics.ucla.edu/software/paintor CONTACT: gkichaev@ucla.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27663504 TI - BCL-2 system analysis identifies high-risk colorectal cancer patients. AB - OBJECTIVE: The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). DESIGN: Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. RESULTS: High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling. CONCLUSIONS: DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors. PMID- 27663506 TI - Response and legislative changes after the Kiss nightclub tragedy in Santa Maria/RS/Brazil: Learning from a large-scale burn disaster. AB - PURPOSE: A major fire occurred on January 27, 2013, at 02:30 at Kiss nightclub in the city of Santa Maria, State of Rio Grande do Sul, in Southern Brazil. In this retrospective report, we aimed to describe the nightclub fire event, its immediate consequences, and evaluated its impact on legislation. Our objective was to disseminate the lessons we learned from this large-scale nightclub fire disaster. METHODS: We conducted a literature review in PubMed and Lilacs database from 2013 to 2015 related to the nightclub Kiss, Santa Maria, fire, burns, and similar events worldwide over the past 15 years. We searched in the general press and online media information sites, and seeking legislation about this topic at the federal level in Brazil. We reported on the legislation changes that resulted from this nightclub fire. RESULTS: Current federal legislation on fire prevention and the scope of public safety, including night clubs and discos, states is the duty of the state and everyone's responsibility, pursuant to Article 144 of the Federal Constitution of Brazil. Thus, the federal union, individual states and municipalities have the power to legislate on fire prevention, and especially to ensure the security of the population. A state law called "Law Kiss", was passed in 2014, establishing standards on safety, prevention and protection against fire in buildings and areas of fire risk in the state of Rio Grande do Sul. On a national level, a law of prevention and fire fighting in Brazil was also drafted after the Santa Maria disaster (Law project no. 4923, 2013). Currently, this bill is still awaiting sanction before it can take effect. CONCLUSION: As we push for enactment of the national law of prevention and fire fighting in Brazil, we will continue emphasizing fire prevention, fire protection, fire fighting, means of escape and proper management. All similar events in this and other countries remind us that similar tragedies may occur anywhere, and that the analysis of facts, previous mistakes, during and after the incident are crucial to our understanding, and will help us lessen the chance of future occurrences. PMID- 27663505 TI - The gastric acid pocket is attenuated in H. pylori infected subjects. AB - OBJECTIVE: Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. DESIGN: We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. RESULTS: Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. CONCLUSIONS: In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket. PMID- 27663507 TI - Does end-tidal capnography confirm tracheal intubation in fresh-frozen cadavers? AB - BACKGROUND: Life-like end-tidal capnography (ETCO2) waveforms have been demonstrated in recently deceased and fresh-frozen cadavers following tracheal intubation, offering potential for high fidelity airway simulation training. As the mechanism for carbon dioxide production is not fully understood, it is possible that oesophageal intubation may also generate a capnograph. Our aim was to measure ETCO2 levels following (1) oesophageal and (2) tracheal intubation in fresh-frozen cadavers, and to observe the size, shape and duration of any capnographic waveform. METHODS: Four fresh frozen cadavers underwent oesophageal intubation by an emergency medicine specialist with confirmation by a second specialist. Hand ventilation with room air via a self-inflating resuscitation bag was provided at 12 breaths per minute for 2 min or until ETCO2 was zero for 10 consecutive breaths. ETCO2 and waveform morphology were examined and video recorded. The oesophagus was then extubated and the process was repeated for tracheal intubation. RESULTS: In no case was oesophageal ETCO2 detected. For two cadavers, life-like ETCO2 waveforms were achieved immediately after tracheal intubation, with maximum ETCO2 achieved by the second breath. In these cases waveform morphology was normal and persistent. CONCLUSIONS: Cadaveric oesophageal intubation did not result in a capnography waveform, simulating live patients. When present, ETCO2 following tracheal intubation showed normal morphology which was sustained for 2 min. However, ETCO2 was not present following tracheal intubation in all cadavers. These results represent instrumentation on the cadavers for the first time after thawing and further work should assess the repeatability of the findings with subsequent intubations. PMID- 27663509 TI - Cirugia Espanola increases its impact factor: Reflections on the necessary evolution of the journal. PMID- 27663508 TI - Computer-assisted client assessment survey for mental health: patient and health provider perspectives. AB - BACKGROUND: The worldwide rise in common mental disorders (CMDs) is posing challenges in the provision of and access to care, particularly for immigrant, refugee and racialized groups from low-income backgrounds. eHealth tools, such as the Interactive Computer-Assisted Client Assessment Survey (iCCAS) may reduce some barriers to access. iCCAS is a tablet-based, touch-screen self-assessment completed by clients while waiting to see their family physician (FP) or nurse practitioner (NP). In an academic-community initiative, iCCAS was made available in English and Spanish at a Community Health Centre in Toronto through a mixed method trial. METHODS: This paper reports the perspectives of clients in the iCCAS group (n = 74) collected through an exit survey, and the perspectives of 9 providers (four FP and five NP) gathered through qualitative interviews. Client acceptance of the tool was assessed for cognitive and technical dimensions of their experience. They rated twelve items for perceived Benefits and Barriers and four questions for the technical quality. RESULTS: Most clients reported that the iCCAS completion time was acceptable (94.5 %), the touch-screen was easy to use (97.3 %), and the instructions (93.2 %) and questions (94.6 %) were clear. Clients endorsed the tool's Benefits, but were unsure about Barriers to information privacy and provider interaction (mean 4.1, 2.6 and 2.8, respectively on a five-point scale). Qualitative analysis of the provider interviews identified five themes: challenges in Assessing Mental Health Services, such as case complexity, time, language and stigma; the Tool's Benefits, including non intrusive prompting of clients to discuss mental health, and facilitation of providers' assessment and care plans; the Tool's Integration into everyday practice; Challenges for Use (e.g. time); and Promoting Integration Effectively, centered on the timing of screening, setting readiness, language diversity, and technological advances. CONCLUSIONS: Participant clients and providers perceived iCCAS as an easy and useful tool for mental health assessments at the Community Health Centre and similar settings. The findings are anticipated to inform further work in this area. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02023957 ; Registered retrospectively 12 Dec. 2013. PMID- 27663511 TI - Comparison of cancer cells in 2D vs 3D culture reveals differences in AKT-mTOR S6K signaling and drug responses. AB - Three-dimensional (3D) cancer models are used as preclinical systems to mimic physiologic drug responses. We provide evidence for strong changes of proliferation and metabolic capacity in three dimensions by systematically analyzing spheroids of colon cancer cell lines. Spheroids showed relative lower activities in the AKT, mammalian target of rapamycin (mTOR) and S6K (also known as RPS6KB1) signaling pathway compared to cells cultured in two dimensions. We identified spatial alterations in signaling, as the level of phosphorylated RPS6 decreased from the spheroid surface towards the center, which closely coordinated with the tumor areas around vessels in vivo These 3D models displayed augmented anti-tumor responses to AKT-mTOR-S6K or mitogen-activated protein kinase (MAPK) pathway inhibition compared to those in 2D models. Inhibition of AKT-mTOR-S6K resulted in elevated ERK phosphorylation in 2D culture, whereas under these conditions, ERK signaling was reduced in spheroids. Inhibition of MEK1 (also known as MAP2K1) led to decreased AKT-mTOR-S6K signaling in 3D but not in 2D culture. These data indicate a distinct rewiring of signaling in 3D culture and during treatment. Detached tumor-cell clusters in vessels, in addition to circulating single tumor cells, play a putative role in metastasis in human cancers. Hence, the understanding of signaling in spheroids and the responses in the 3D models upon drug treatment might be beneficial for anti-cancer therapies. PMID- 27663510 TI - Characterization of proteome dynamics during growth in oleate reveals a new peroxisome-targeting receptor. AB - To optimally perform the diversity of metabolic functions that occur within peroxisomes, cells must dynamically regulate peroxisome size, number and content in response to the cell state and the environment. Except for transcriptional regulation little is known about the mechanisms used to perform this complicated feat. Focusing on the yeast Saccharomyces cerevisiae, we used complementary high content screens to follow changes in localization of most proteins during growth in oleate. We found extensive changes in cellular architecture and identified several proteins that colocalized with peroxisomes that had not previously been considered peroxisomal proteins. One of the newly identified peroxisomal proteins, Ymr018w, is a protein with an unknown function that is similar to the yeast and human peroxisomal targeting receptor Pex5. We demonstrate that Ymr018w is a new peroxisomal-targeting receptor that targets a subset of matrix proteins to peroxisomes. We, therefore, renamed Ymr018w, Pex9, and suggest that Pex9 is a condition-specific targeting receptor that enables the dynamic rewiring of peroxisomes in response to metabolic needs. Moreover, we suggest that Pex5-like receptors might also exist in vertebrates. PMID- 27663512 TI - Trends and Regional Variation in Hospital Mortality, Length of Stay and Cost in Hospital of Ischemic Stroke Patients in Alberta Accompanying the Provincial Reorganization of Stroke Care. AB - OBJECTIVES: This study aimed to evaluate the trends and regional variation of stroke hospital care in 30-day in-hospital mortality, hospital length of stay (LOS), and 1-year total hospitalization cost after implementation of the Alberta Provincial Stroke Strategy. METHODS: New ischemic stroke patients (N = 7632) admitted to Alberta acute care hospitals between 2006 and 2011 were followed for 1 year. We analyzed in-hospital mortality with logistic regression, LOS with negative binomial regression, and the hospital costs with generalized gamma model (log link). The risk-adjusted results were compared over years and between zones using observed/expected results. RESULTS: The risk-adjusted mortality rates decreased from 12.6% in 2006/2007 to 9.9% in 2010/2011. The regional variations in mortality decreased from 8.3% units in 2008/2009 to 5.6 in 2010/2011. The LOS of the first episode dropped significantly in 2010/2011 after a 4-year slight increase. The regional variation in LOS was 15.5 days in 2006/2007 and decreased to 10.9 days in 2010/2011. The 1-year hospitalization cost increased initially, and then kept on declining during the last 3 years. The South and Calgary zones had the lowest costs over the study period. However, this gap was diminishing. CONCLUSIONS: After implementation of the Alberta Provincial Stroke Strategy, both mortality and hospital costs demonstrated a decreasing trend during the later years of study. The LOS increased slightly during the first 4 years but had a significant drop at the last year. In general, the regional variations in all 3 indicators had a diminishing trend. PMID- 27663513 TI - Phosphate uptake kinetics and tissue-specific transporter expression profiles in poplar (Populus * canescens) at different phosphorus availabilities. AB - BACKGROUND: Phosphorus (P) is a major plant nutrient. It is transported into and allocated inside plants by four families of phosphate transporters (PHT1 to PHT4) with high or low affinity to phosphate. Here, we studied whole-plant P uptake kinetics and expression profiles of members of the PHT families under high, intermediate and low P availability in the woody crop poplar (Populus * canescens) in relation to plant performance. RESULTS: Poplars exhibited strong growth reduction and increased P use efficiency in response to lower P availabilities. The relative P uptake rate increased with intermediate and decreased with low P availability. This decrease was not energy-limited because glucose addition could not rescue the uptake. The maximum P uptake rate was more than 13-times higher in P-starved than in well-supplied poplars. The Km for whole root uptake ranged between 26 MUM and 20 MUM in poplars with intermediate and low P availability, respectively. In well-supplied plants, only low uptake rate was found. The minimum concentration for net P uptake from the nutrient solution was 1.1 MUM. All PHT1 members studied showed significant up-regulation upon P starvation and were higher expressed in roots than leaves, with the exception of PtPHT1;3. PtPHT1;1 and PtPHT1;2 showed root- and P starvation-specific expression. Various members of the PHT2, PHT3 and PHT4 families showed higher expression in leaves than in roots, but were unresponsive to P deprivation. Other members (PtPHT3;1, PtPHT3;2, PtPHT3;6, PtPHT4;6 to PtPHT4;8) exhibited higher expression in roots than in leaves and were in most cases up-regulated in response to P deficiency. CONCLUSIONS: Expression profiles of distinct members of the PHT families, especially those of PHT1 were linked with changes in P uptake and allocation at whole-plant level. The regulation was tissue-specific with lower P responsiveness in leaves than in roots. Uptake efficiency for P increased with decreasing P availability, but could not overcome a threshold of about 1 MUM P in the nutrient solution. Because the P concentrations in soil solutions are generally in the lower micro-molar range, even below the apparent Km-values, our findings suggest that bare-rooted poplars are prone to suffer from P limitations in most environments. PMID- 27663516 TI - The unexpected complexity of bacterial genomes. AB - Gene organization and control are described by models conceived in the 1960s. These models explain basic gene regulatory mechanisms and underpin current genome annotation. However, such models struggle to explain recent genome-scale observations. For example, accounts of RNA synthesis initiating within genes, widespread antisense transcription and non-canonical DNA binding by gene regulatory proteins are difficult to reconcile with traditional thinking. As a result, unexpected observations have often been dismissed and downstream consequences ignored. In this paper I will argue that, to fully understand the biology of bacterial chromosomes, we must embrace their hidden layers of complexity. PMID- 27663515 TI - Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. AB - BACKGROUND: Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20-40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment. Because radiotherapy has immunomodulatory effects on the tumor microenvironment, it has the potential to synergize with immunotherapy and augment tumor response. NCT02318771 is a phase 1 clinical trial designed to investigate the immunomodulatory effects of radiation therapy in combination with pembrolizumab. CASE PRESENTATION: The patient is a 64 year-old male with metastatic clear cell renal cell carcinoma, Fuhrman grade 4, pathologically staged as T3 N0. Metastatic disease was well controlled for several years with sunitinib. Following disease progression, he was switched to axitinib. When disease progression continued, the patient was enrolled in NCT02318771, a phase 1 clinical trial combining radiotherapy and pembrolizumab. The patient experienced unusually rapid disease progression during treatment, which was confirmed by repeated CT scans to rule out pseudoprogression. Tissue biopsies and peripheral blood draws were obtained before, during, and after treatment. Samples were analyzed to provide plausible rationale for rapid treatment failure. CONCLUSIONS: Biomarker analysis demonstrated an absence of TILs, which may be a cause of treatment failure as pembrolizumab works through T cell-dependent mechanisms. Furthermore, the presence of other non-redundant immune checkpoints in the periphery and tumor microenvironment presents a treatment challenge. Additionally, the radiation dose and fractionation schedule may have played a role in treatment failure as these factors play a role in the effect radiotherapy on the tumor microenvironment as well as the potential for synergy with immunotherapy. TRIAL REGISTRATION: An Exploratory Study to Investigate the Immunomodulatory Activity of Radiation Therapy (RT) in Combination With MK-3475 in Patients With Recurrent/Metastatic Head and Neck, Renal Cell Cancer, Melanoma and Lung Cancer, NCT02318771 . PMID- 27663514 TI - Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation. AB - BACKGROUND: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms. STUDY DESIGN: We investigated the benefits of pre reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage. RESULTS: Serum creatinine measurement showed that treated animals recovered glomerular function quicker than the Vehicle group. However, no difference was observed in tubular function recovery, and elevated level of urinary NGal (Neutrophil gelatinase-associated lipocalin) and plasma AST (Aspartate Aminotransferase) were detected, indicating that treatment did not influence IRI-mediated tubular cell necrosis. Regarding chronic graft outcome, rhC1INH significantly prevented fibrosis development and improved function. Immunohistochemistry and western blot showed decreased invasion by macrophages and T lymphocytes, and reduction of epithelial to mesenchymal transition. We determined the effect of treatment on complement activation with immunofluorescence analyses at 30 min post reperfusion, showing an inhibition of C4d deposition and MBL staining in treated animals. CONCLUSIONS: In this model, the inhibition of complement activation by rhC1INH at reperfusion, while not completely counteracting IRI, limited immune system activation, significantly improving graft outcome on the short and long term. PMID- 27663517 TI - Utilizing health analytics in improving the performance of healthcare services: A case study on a tertiary care hospital. AB - Among the most common and chronic problems in the healthcare system worldwide is the crowding of emergency rooms (ER); leading to many serious complications. King Faisal Specialist Hospital and Research Center utilized health analytics methods to identify areas of deficiency and suggest potential improvements to ER performance. The project implemented solutions and monitored two indicators; ER length of stay (LOS), reflecting efficiency, and percentage of patients leaving without treatment, reflecting effectiveness of the ER. A retrospective analysis of 26,948 ER encounters in 2014 was done in January 2015. Analytics techniques were used to suggest process redesign based on results. Two recommendations were implemented; a Fast-Track for lower acuity ER patients and an internal waiting area, for those patients who can stay vertical and spare an ER bed. 32.8% of ER patients had lower acuity levels and less than 0.5% of them were admitted to the hospital. After implementing the two solutions, the total ER LOS was reduced from 20h in 2014 to less than 12h in 2016; 40% improvement. The percentages of patients left without being seen stayed around 3.5%, while the percentages of patients left before complete treatment was significantly reduced from 13.5% in 2014 to 5.5% in 2016. Consequently, the total percentage of patients left without treatment was reduced from 17% in 2014 to 9% in 2016, with 50% improvement. All other factors were the same, including numbers of ER visits, Patient Acuity Level, working staff, working hours, and the count of ER beds. Health analytics methods can be used to identify areas of deficiency, potential improvements, and recommend effective solutions to positively enhance ER performance. More solutions should be examined such as team triaging, patients palmar scanning, and placing a physician in triage. Additionally, more indicators should be monitored, such as the effectiveness of ER treatment-including the rates of revisits. PMID- 27663518 TI - Enhancing outpatient clinics management software by reducing patients' waiting time. AB - The Kingdom of Saudi Arabia (KSA) gives great attention to improving the quality of services provided by health care sectors including outpatient clinics. One of the main drawbacks in outpatient clinics is long waiting time for patients-which affects the level of patient satisfaction and the quality of services. This article addresses this problem by studying the Outpatient Management Software (OMS) and proposing solutions to reduce waiting times. Many hospitals around the world apply solutions to overcome the problem of long waiting times in outpatient clinics such as hospitals in the USA, China, Sri Lanka, and Taiwan. These clinics have succeeded in reducing wait times by 15%, 78%, 60% and 50%, respectively. Such solutions depend mainly on adding more human resources or changing some business or management policies. The solutions presented in this article reduce waiting times by enhancing the software used to manage outpatient clinics services. Both quantitative and qualitative methods have been used to understand current OMS and examine level of patient's satisfaction. Five main problems that may cause high or unmeasured waiting time have been identified: appointment type, ticket numbering, doctor late arrival, early arriving patient and patients' distribution list. These problems have been mapped to the corresponding OMS components. Solutions to the above problems have been introduced and evaluated analytically or by simulation experiments. Evaluation of the results shows a reduction in patient waiting time. When late doctor arrival issues are solved, this can reduce the clinic service time by up to 20%. However, solutions for early arriving patients reduces 53.3% of vital time, 20% of the clinic time and overall 30.3% of the total waiting time. Finally, well patient-distribution lists make improvements by 54.2%. Improvements introduced to the patients' waiting time will consequently affect patients' satisfaction and improve the quality of health care services. PMID- 27663520 TI - Early outcome of degenerated self-expandable sutureless aortic prostheses treated with transcatheter valve implantation: A pilot series. PMID- 27663519 TI - Emergence of human caliciviruses among diarrhea cases in southwest China. AB - BACKGROUND: Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China. METHODS: The study was conducted in four hospitals in Kunming city, Yunnan province, from June 2014 to July 2015. Stool specimens were collected from 1,121 diarrhea cases and 319 healthy controls in outpatient departments. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect NoV (GI, GII) and SaV. Sequencing was applied to confirm the three viral infections and phylogenetic analysis was performed to determine their genotypes. A structured questionnaire was used to record the demographic information and clinical symptoms of subjects. RESULTS: HuCV was detected at an 11.0 % infection rate in 1,121 diarrhea cases and at 3.4 % rate in 319 non diarrhea subjects (p < 0.0001, OR = 3.5, 95 % CI 1.8-6.5). The prevalence of the NoV genogroup GII and genotype GII.4 in diarrhea cases was significantly higher than that found in healthy controls (p < 0.0001, p = 0.018, respectively). NoV GII (n = 118, 10.5 %) was the most common HuCV subtype in diarrhea cases, followed by SaV (n = 3, 0.3 %) and NoV GI (n = 2, 0.2 %). Of 118 NoV GII strains isolated from diarrhea patients. GII.4 (n = 55, 46.6 %) was the predominant strain, followed by GII.3 (n = 28, 23.7 %), GII.12 (n = 25, 21.2 %), GII.17 (n = 8, 6.8 %), and GII.5 (n = 2, 1.7 %). Of the 55 GII.4 strains, the GII.4 Sydney 2012 variant had absolutely predominant prevalence (n = 52, 94.5 %), followed by the NoV GII.4-2006b variant (n = 3, 5.5 %). The GII.4 Orleans 2009 variant was not found in diarrhea cases of the study. CONCLUSIONS: NoV GII was the major genogroup and GII.4 was the most predominant strain detected in diarrhea patients. The GII.17 is an emergent variant in sporadic diarrhea and might become the predominant strain in diarrhea cases in the near future. Rapid, accurate detection kits need to be developed to help us find and treat NoV-associated diarrhea in clinical settings in a timely manner. PMID- 27663521 TI - Evaluating the stented bovine jugular vein graft valve (Melody) for mitral valve replacement: New echocardiographic criteria to evaluate novel techniques. PMID- 27663522 TI - Are attempts at regulating flow through systemic-to-pulmonary arterial shunts still valid? PMID- 27663523 TI - Rethinking the gold standard of correction for paravalvular leak: Why correct when you can prevent? PMID- 27663524 TI - Quantifying dimensions of physical behavior in chronic pain conditions. AB - BACKGROUND: Chronic pain, defined as persistent or recurrent pain lasting longer than 3 months, is a frequent condition affecting an important percent of population worldwide. Pain chronicity can be caused by many different factors and is a frequent component of many neurological disorders. An important aspect for clinical assessment and design of effective treatment and/or rehabilitation strategies is to better understand the impact of pain on domains of functioning in everyday life. The aim of this study was to identify the objectively quantifiable features of physical functioning in daily life and to evaluate their effectiveness to differentiate behavior among subjects with different pain conditions. METHOD: Body worn sensors were used to record movement data during five consecutive days in 92 subjects. Sensor data were processed to characterize the physical behavior in terms of type, intensity, duration and temporal pattern of activities, postures and movements performed by subjects in daily life. Metrics quantifying these features were subsequently used to devise composite scores using a factor analysis approach. The severity of clinical condition was assessed using a rating of usual pain intensity on a 10-cm visual analog scale. The relationship between pain intensity and the estimated metrics/composite scores was assessed using multiple regression and discriminant analysis. RESULTS: According to the factor analysis solution, two composite scores were identified, one integrating the metrics quantifying the amount and duration of activity periods, and the other the metrics quantifying complexity of temporal patterns, i.e., the diversity of body movements and activities, and the manner in which they are organized throughout time. All estimated metrics and composite scores were significantly different between groups of subjects with clinically different pain levels. Moreover, analysis revealed that pain intensity seemed to have a more significant impact on the overall physical behavior, as it was quantified by a global composite score, whereas the type of chronic pain appeared to influence mostly the complexity of the temporal pattern. CONCLUSION: The methodology described could be informative for the design of objective outcome measures in chronic pain management/rehabilitation programs. PMID- 27663525 TI - Risk factors for pneumothorax in advanced and/or metastatic soft tissue sarcoma patients during pazopanib treatment: a single-institute analysis. AB - BACKGROUND: After the approval of pazopanib for the treatment of soft tissue sarcoma (STS), pneumothorax was reported as an unexpected adverse event during pazopanib treatment. The incidence and risk factors of pneumothorax during pazopanib treatment for STSs have not been established yet. METHODS: We retrospectively reviewed the cases of all of the STS patients treated with pazopanib between November 2012 and December 2014 at our institute and evaluated the prevalence, incidence, treatment details and risk factors for pneumothorax in the STS patients during pazopanib treatment. RESULTS: A total of 58 patients were enrolled; 45 of them had lung and/or pleural lesions at the start of pazopanib treatment. During the median follow-up time of 219 days (range 23-659), 13 pneumothorax events occurred in six patients; the prevalence and incidence of pneumothorax were 10.3 % and 0.56 per treatment-year, respectively. The median onset of pneumothorax was day 115 (range 6-311). No patients died of pneumothorax, but pazopanib was interrupted in 10 events and chest drainage was performed in eight events. Pazopanib continuation or restart after the recovery from pneumothorax was conducted after 9 of the 13 events. The median progression free survival of patients with and without pneumothorax events were 144 and 128 days (p = 0.89) and the median overall survival periods were 293 and 285 days (p = 0.69), respectively. By logistic regression analyses, the maximum diameter of the lung metastases >= 30 mm (OR 13.3, 95 % CI 1.1-155.4, p = 0.039) and a history of pneumothorax before the pazopanib induction (OR 16.6, 95 % CI 1.1 256.1, p = 0.045) were significantly predictive of pneumothorax. CONCLUSIONS: In our retrospective analysis, pneumothorax was observed in 10.3 % of 58 STS patients during pazopanib treatment. The diameter of the lung metastases and a history of pneumothorax could be useful for evaluating the risk of pneumothorax in pazopanib treatment. PMID- 27663526 TI - Evaluation of functional rehabilitation physiotherapy protocol in the postoperative patients with anterior cruciate ligament reconstruction through clinical prognosis: an observational prospective study. AB - BACKGROUND: The aim of the study was to evaluate the evolution of patients subject to physical treatment based on guidelines of functional rehabilitation after surgery anterior cruciate ligament reconstruction. METHODS: This is a prospective study of 177 patients with anterior cruciate ligament injury, who underwent surgery and physical therapy guideline conducted in an orthopedic clinic in Sao Paulo, southeastern Brazil. The clinical evolution of patients was made according to Lysholm and IKDC questionnaire on the 1st day after surgery with 30, 90 and 180 days of treatment. RESULTS: There was statistically significant increase in the gross values of Lysholm and IKDC questionnaires during the treatment (p < 0.001), which indicates progressive gain of function. According to the scores obtained from the IKDC, it can be observed that in stage 1 the average progress was 53.5 %, falling to 50 % in stage 2, and 26.1 % in stage 3. As to Lysholm score, it started with 87.7 %, falling to 62.6 % in the second stage and 7 % in the third stage, both statistically significant (p < 0.001). The rehabilitation-oriented functional objectives priority is to quickly get the exercises to gain breadth, strength and proprioception, optimizing and improving the integration of the athlete back to sport. CONCLUSION: Synthesizing the gradual gain of function and according to clinical outcomes assessed by IKDC and Lysholm, the functional guideline presented may be considered an alternative for rehabilitation of patients in postoperative anterior cruciate ligament. PMID- 27663528 TI - G-Quadruplexes in DNA Replication: A Problem or a Necessity? AB - DNA replication is a highly regulated process that ensures the correct duplication of the genome at each cell cycle. A precise cell type-specific temporal program controls the duplication of complex vertebrate genomes in an orderly manner. This program is based on the regulation of both replication origin firing and replication fork progression. G-quadruplexes (G4s), DNA secondary structures displaying noncanonical Watson-Crick base pairing, have recently emerged as key controllers of genome duplication. Here we discuss the various means by which G4s affect this fundamental cellular process. PMID- 27663527 TI - Plasmodium vivax msp-3alpha polymorphisms: analysis in the Indian subcontinent. AB - BACKGROUND: Plasmodium vivax is the most widely distributed human malaria parasite and accounts for approximately the same number of malaria cases as Plasmodium falciparum in India. Compared with P. falciparum, P. vivax is difficult to eradicate because of its tendency to cause relapses, which impacts treatment and control strategies. The genetic diversity of these parasites, particularly of the merozoite surface protein-3 alpha (msp-3alpha) gene, can be used to help develop a potential vaccine. The present study aimed to investigate the genetic diversity of P. vivax using the highly polymorphic antigen gene msp 3alpha and to assess the suitability of using this gene for population genetic studies of P. vivax isolates and was carried out in 2004-06. No recent study has been reported for MSP 3alpha in the recent decade in India. Limited reports are available on the genetic diversity of the P. vivax population in India; hence, this report aimed to improve the understanding of the molecular epidemiology of the parasite by studying the P. vivax msp-3alpha (Pvmsp-3alpha) marker from P. vivax field isolates from India. METHODS: Field isolates were collected from different sites distributed across eight states in India. A total of 182 blood samples were analysed by a nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique using the HhaI and AluI restriction enzymes to determine genetic msp-3alpha variation among clinical P. vivax isolates. RESULTS: Based on the length variants of the PCR products of Pvmsp 3alpha gene, three allele sizes, Type A (1.8 kb), Type B (1.5 kb) and Type C (1.2 kb) were detected among the 182 samples. Type A PCR amplicon was more predominant (75.4 %) in the samples compared with the Type B (14.3 %) and Type C (10.0 %) polymorphisms. Among all of the samples analysed, 8.2 % were mixed infections detected by PCR alone. Restriction fragment length polymorphism (RFLP) analysis involving the restriction enzymes AluI and HhaI generated fragment sizes that were highly polymorphic and revealed substantial diversity at the nucleotide level. CONCLUSIONS: The present study is the first extensive study in India using the Pvmsp-3alpha marker. The results indicated that Pvmps-3alpha, a polymorphic genetic marker of P. vivax, exhibited considerable variability in infection prevalence in field isolates from India. Additionally, the mean multiplicity of infection observed at all of the study sites indicated that P. vivax is highly diverse in nature in India, and Pvmsp-3alpha is likely an effective and promising epidemiological marker. PMID- 27663529 TI - Assessment of Comorbidity Burden and its Association With Functional Rehabilitation Outcome After Stroke or Hip Fracture: A Systematic Review and Meta Analysis. AB - BACKGROUND: A well-grounded functional prognosis during triage for rehabilitation is important, especially in older patients who experience the burden of comorbidity. However, it remains unclear what impact comorbidity has on functional outcome after rehabilitation. AIM: To investigate the associations between comorbidity indexes and functional outcome after inpatient stroke or hip fracture rehabilitation. Furthermore, to identify which method of comorbidity assessment best reveals this relationship. DESIGN: Systematic review and meta analysis. METHODS: An extensive search in PubMed, EMBASE, COCHRANE, Web of Science, and CINAHL of cited references and gray literature was carried out on March 4, 2016. This meta-analysis was conducted in agreement with the guidelines for Preferred Reporting Items for Systematic reviews and Meta-Analyses. Studies were included if participants were adult patients with a stroke or hip fracture, participants received inpatient rehabilitation, comorbidity was assessed with a valid index, and functional status was an outcome measure. Two reviewers independently extracted data; according to the predefined data extraction plan, included studies were independently evaluated on risk of bias. RESULTS: Twenty studies were eligible for review, and 7 studies were included in the meta analysis. The pooled correlation between comorbidity and functional status at discharge was -0.43 [-0.69; -0.06]. Presence and strength of correlations differed between comorbidity indexes. Charlson index: range = 0.0 to -0.88 and 0% 1% explained variance (%var). Cumulative illness rating scale (CIRS) total or cumulative: range = -0.02 to -0.34 and unknown %var. CIRS-severity index: range = -0.25 to -0.40 and 12-16 %var. Comorbidity-severity index: range = -0.39 and 0.47 and 5 %var. Liu index: range = -0.28 to -0.50 and 4-7 %var. When the index contained a severity weighting, the associations were more evident. CONCLUSIONS: An association between comorbidity burden and functional outcome exists, albeit modest. Assessment of severity weighted comorbidity is preferred for estimating the functional prognosis after stroke and hip fracture rehabilitation. PMID- 27663531 TI - Modification of aftertaste with a menthol mouthwash reduces food wanting, liking, and ad libitum intake of potato crisps. AB - This research investigated the effect of modifying the aftertaste of potato crisps on (1) temporal sensory perception and (2) appetite using three mouthwash conditions (no mouthwash, a water mouthwash, and a menthol mouthwash). For the sensory study, 17 screened female subjects were trained on the Temporal Dominance of Sensations (TDS) methodology. Subjects undertook TDS to monitor all sensory attributes during the mastication of a 2 g crisp until swallowing (at 20s), then conducted the mouthwash, and then continued the TDS task to monitor aftertaste until 90s. For the appetite study, 36 subjects (18 male, 18 female) completed 100 mm Visual Analogue Scales (VAS) for desire, liking, hunger, and thirst, followed by an ad libitum eating task. For the VAS scales testing, subjects chewed and swallowed a 2 g crisp, and then immediately conducted the mouthwash before completing the VAS scales. For the ad libitum task, subjects were given 12 min to consume as many crisps as they desired on a plate (up to 50 g). Every three minutes they were required to conduct a mouthwash. TDS results showed that in comparison with no mouthwash, the water mouthwash significantly reduced aftertaste attributes such as savoury, salty, and fatty mouthcoating, and the menthol mouthwash significantly increased aftertaste attributes of cooling, minty, and tingly. The water mouthwash did not influence desire and liking of crisps, or hunger and thirst. The water mouthwash did not influence ad libitum intake of the crisps over a 12 min period. The menthol mouthwash significantly reduced desire and liking of the crisps, as well as hunger and thirst. Furthermore, the menthol mouthwash significantly reduced ad libitum crisp intake by 29% over the 12 min period. PMID- 27663532 TI - Commentary: Does Mandibular Distraction Vector Influence Airway Volumes and Outcome? PMID- 27663530 TI - LL-37 but Not 25-Hydroxy-Vitamin D Serum Level Correlates with Healing of Venous Leg Ulcers. AB - Human cathelicidin, LL-37, is small antimicrobial peptide, which reveals also some immunomodulatory and proangiogenic properties and, therefore, may promote wound healing. The expression of LL-37 is controlled by various factors, including vitamin D. Thus, any disturbances in vitamin D level may influence LL 37 production and, possibly, affect wound healing. Since deficiency of vitamin D was identified as a common problem in the population, this proof of concept study aimed to verify the relationship between serum levels of LL-37, vitamin D, and healing rate of venous leg ulcers. The study involved small group (n = 19) of patients with venous leg ulcers. Apart from non-venous ulcer aethiology, compression intolerance, active vein thrombosis, and wound infection, the exclusion criteria concerned also kidney insufficiency. The results of the analysis of wound healing rates were correlated with patients' serum levels of 25(OH) vitamin D and LL-37. In addition, serum levels of pro-inflammatory cytokines (IL-6, IL-8, and TNF) were analyzed. We have found strong association between serum concentrations of LL-37 and the healing rates in patients with leg ulcers. Despite the fact that 25(OH) vitamin D levels in all patients were below the normal range, they did not show any correlation with healing rates. Furthermore, no association was observed between serum levels of 25(OH) vitamin D and LL-37. No significant correlation between tested pro-inflammatory cytokines and healing rate, LL-37, or 25(OH) vitamin D levels was also observed. Regardless of small study group, our results suggest that the assessment of serum concentration of LL-37, but not 25-hydroxy vitamin D, may help in predicting the wound healing efficacy. Moreover, this assessment may be useful in pre-selection of patients, which could benefit from local treatment with exogenous LL-37. PMID- 27663533 TI - Dynamic Evaluation of Lavage Efficacy in Upper Compartment of the Temporomandibular Joint. AB - PURPOSE: The aim of this study was to determine the most efficient temporomandibular joint (TMJ) lavage technique for complete irrigation and removal of synovial fluid. The corresponding total lavage fluid volume needed also was investigated. MATERIALS AND METHODS: Three-dimensional TMJ lavage models of the classic double- and single-needle techniques with modified cannula sizes (diameters, 2.4 and 0.8 mm) were generated based on a constructed upper compartment model. Models were integrated with 2-phase flow models to predict fractional fluid volume (alpha value) changes of lavage saline and synovial fluid within the upper compartment of the TMJ. Fluid flow diagrams, velocity vectors, and intra-articular pressure data were collected and compared among the models. Models were validated by clinical synovial fluid concentration analyses, with vitamin B12 used as an internal standard. RESULTS: In all 8 models, lavage fluid initially gathered around the inflow portal, with a stable mixture of synovial and lavage fluids eventually being established in the compartment. Use of the double-needle technique with a large inflow portal resulted in thorough lavage (alpha = 100%). When the single-needle or Shepard cannula technique was used, some areas within the upper compartment remained devoid of brisk flow. The 2.4-mm inflow model coupled with a 0.8-mm outflow portal resulted in a stably and persistently high intra-articular pressure (>2.7 * 104 Pa). A minimum volume of 109 mL of lavage fluid was necessary for complete replacement of synovial fluid by saline. CONCLUSIONS: When a 2.4-mm inflow portal needle was applied, a lavage rate of 100% was obtained with a minimum lavage volume of 109 mL. Using a small inflow portal could lead to inadequate flow, residual synovial fluid, and, ultimately, treatment failure. PMID- 27663535 TI - Sialosis, Gout Induced or Idiopathic? Case Report. AB - Sialosis is observed in relation to diabetes, alcoholism, and malnutrition. An assumed relation between gout and sialosis is probably based on confusion that originated from the therapeutic use of phenylbutazone for gout and the sialadenitis that the medication caused. This report describes a case of sialosis in a patient with a longstanding history of gout that was idiopathic in origin. PMID- 27663534 TI - Is There an Association Between Temporomandibular Joint Effusion and Arthralgia? AB - PURPOSE: The literature on joint effusion (JE) and its association with clinical and radiologic variables in patients with temporomandibular disorders (TMDs) is inconsistent and is characterized by multiple methodologic limitations. The primary aim of this investigation was to evaluate the association between magnetic resonance imaging (MRI) identified JE and temporomandibular joint (TMJ) arthralgia. The secondary aim of this investigation was to determine the association between JE and other clinical and MRI-identified soft tissue characteristics. MATERIALS AND METHODS: A retrospective cohort study was conducted. Clinical and soft tissue imaging assessments were carried out according to the Diagnostic Criteria for Temporomandibular Disorders guidelines. The dependent variable was JE and the primary independent variable was arthralgia. The secondary independent variables were TMJ pain-associated characteristics and MRI-identified variables. When applicable, Pearson chi2 or t test was used to determine the statistical associations between JE and clinical characteristics and between JE and MRI-identified variables. Furthermore, generalized estimating equation (GEE) modeling was conducted to determine which of the independent clinical and MRI-identified variables were associated with JE. RESULTS: Data for 158 participants, representing 312 joints, were extracted. The mean age of the female sample (59.4%) was 31 +/- 11.1 years and that of the male sample (40.6%) was 29.8 +/- 9.7 years. No association was found between JE and arthralgia. However, statistically significant associations were found between JE and lateral disc rotation (P = .001) and between JE and disc position in the coronal and sagittal planes (P = .001). The GEE model suggested that disc displacement with reduction (odds ratio = 2.5) was a statistically relevant contributing factor for JE in the absence of degenerative joint disease. CONCLUSION: Results associated JE with the position of the disc in the sagittal plane. No association was found between JE and arthralgia or TMJ pain-associated clinical characteristics in patients with TMDs. PMID- 27663536 TI - The Use of Sequential VEGF- and BMP2-Releasing Biodegradable Scaffolds in Rabbit Mandibular Defects. AB - PURPOSE: Promising developments have materialized in reconstructive surgical procedures with the applications of tissue engineering. In our study, we used tissue scaffolds fabricated from polylactic acid-polyethylene glycol (PLLA-PEG) copolymers to ensure different release rates of selective growth factors recombinant human bone morphogenetic protein 2 [rhBMP-2] and vascular endothelial growth factor (rhVEGF165) in the repair of mandibular bone defects. MATERIALS AND METHODS: In our experimental study, 54 New Zealand rabbits were used. The rabbits were separated into 4 groups: group I (control group), PLLA-PEG scaffold only; group II, PLLA-PEG scaffold plus rhBMP-2 application; group III, PLLA-PEG scaffold plus VEGF165 application; and group IV, PLLA-PEG scaffold plus rhBMP-2 and VEGF165 applications. The rabbits were killed at 4 and 8 weeks postoperatively, and histopathologic and immunohistochemical assessments were performed. RESULTS: The greatest bone volume was observed in rhBMP-2-containing groups, the greatest vessel volume was observed in VEGF165-containing groups; however, the scaffold containing rhBMP-2 and VEGF165 provided the best outcomes in conjunction with increased remodeling of the new bone. CONCLUSIONS: The use of polymer tissue scaffolds that release rhVEGF165 and rhBMP-2 in coordination and mimic the natural healing process in the regeneration of especially complex tissues, such as bone, is a promising treatment alternative in the field of reconstructive surgery. PMID- 27663537 TI - Evaluation of Sialendoscopy-Assisted Treatment of Submandibular Gland Stones. AB - PURPOSE: The aim of the present study was to evaluate the therapeutic efficiency of sialendoscopy-assisted operations in the treatment of submandibular gland stones. MATERIALS AND METHODS: The data from 8 patients with sialolithiasis who underwent sialendoscopy from August 2015 to January 2016 at the Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University (Shenyang, China) were retrospectively reviewed. All the patients had undergone preoperative technetium-99m pertechnetate salivary gland scintigraphy. The results revealed that the salivary glands exhibited normal or slightly reduced uptake and excretion dysfunction. Computed tomography examinations revealed stones located in the intraductal area near the glands or in the branches that could not be removed owing to their deep locations within the mouth. Therefore, an endoscope was inserted, the stones were located intraductally using sialendoscopy, and a transcervical incision was made to remove the stones and preserve the submandibular gland. RESULTS: The stones were completely removed, and the submandibular gland was preserved in all cases. The patients recovered well postoperatively, and no complications developed. CONCLUSIONS: Our results suggest that sialendoscopy-assisted sialolithectomy is an effective and safe surgical technique for the removal of proximal and intraglandular submandibular gland stones. The patients' quality of life had obviously improved postoperatively. PMID- 27663538 TI - Whole-Arch Single-Stage Free Flap Reconstruction and Rehabilitation of the Mandible: A Case Report and Technical Considerations on a New Technique. AB - The purpose of this report is to describe the techniques used in the reconstruction of a complete angle-to-angle mandibular defect in the absence of any remaining mandibular teeth. Because no remaining dental or occlusal landmarks remain in such a case, additional challenges must be considered. PMID- 27663539 TI - Postoperative Delirium Following Orthognathic Surgery in a Young Patient. AB - Delirium is an organic mental syndrome with acute onset characterized by diffuse brain dysfunction and neural activity disorganization. It is usually related to cognition and perception changes, decreased level of consciousness, and disorganization of thoughts that are unrelated to previous dementia. Occurrence is more frequent in patients with previous degenerative disease and elderly patients, especially those older than 85 years. Although the pathophysiology is not totally known, studies have shown that, among the main factors that lead to delirium, the drugs used for general anesthesia induction are the most relevant (hypnotics, anticholinergic drugs, and H2 receptor blockers), especially those used in long surgical procedures. This report describes the case of a 24-year-old woman with a noncontributory medical and psychological history. She underwent bimaxillary orthognathic surgery with a total general anesthesia time of 7 hours. Postoperatively, she developed agitation, confusion, and delirium. After a psychiatry consult and discussion with the anesthesia team, the diagnosis of psychotic break owing to late postoperative delirium was established. PMID- 27663540 TI - p16 Immunohistochemistry Is a Useful Diagnostic Adjunct in Cases of Metastatic Cervical Carcinoma of Unknown Origin. AB - PURPOSE: Metastatic cervical carcinoma of unknown primary (MCCUP) is increasing in frequency owing in part to rising human papillomavirus (HPV)-driven oropharyngeal carcinoma. Identifying the primary site is valuable, because it is associated with increased survival and decreased morbidity. HPV-positive cervical nodal disease focuses attention on the oropharynx for directed biopsy examinations, including tonsillectomy. When the primary is small, carcinoma might not be apparent by traditional hematoxylin and eosin (H&E) staining alone. MATERIALS AND METHODS: This report describes 2 cases of p16-positive MCCUP in which a small primary carcinoma was not readily identified in surgical specimens using H&E staining. RESULTS: Additional evaluation of the specimens with p16 immunohistochemistry (IHC) showed carcinoma in these 2 cases. CONCLUSIONS: When H&E staining does not show carcinoma in cases of MCCUP, p16 IHC should be considered given the high prevalence of HPV-positive MCCUP and the potential for identification of a small primary tumor that might otherwise be missed with H&E staining. PMID- 27663542 TI - Serum fasting GLP-1 and GLP-2 associate with intestinal adaptation in pediatric onset intestinal failure. AB - AIM: Glukagon-like-peptide-1 (GLP-1) and -2 (GLP-2), produced by intestinal L cells, are key hormones regulating intestinal transit, secretion, absorption, and mucosal growth. We evaluated naive fasting serum GLP-1 and GLP-2 levels in pediatric intestinal failure (IF). METHODS: Fifty-five IF patients with median age 4.2 (IQR 1.3-12) years and 47 matched healthy controls underwent measurement of fasting serum GLP-1 and GLP-2. RESULTS: Serum GLP-2 [19.9 (13.8-27.9) vs 11.6 (7.0-18.6) ng/mL, P < 0.001], but not GLP-1 [6.1 (4.0-15.7) vs 6.4 (3.9-10.7) ng/mL, P = 0.976], levels were increased in IF patients. Serum GLP-2 concentrations were higher in patients with small bowel-colic continuity [21.1 (15.0-30.7) ng/mL] compared to patients with an endostomy [10.4 (6.6-17.9) ng/mL, P = 0.028], whereas no association with preservation of ileum or ileocecal valve was observed. During PN delivery, GLP-2 inversely associated with remaining small bowel length (r = -0.500, P = 0.041) and frequency of PN infusions (r = -0.549, P = 0.042). Serum GLP-1 levels were lower in patients receiving PN currently [4.1 (2.8-5.1)] compared to patients, who had weaned off PN [6.5 (5.1-21.1), P = 0.005], and correlated positively with duration of PN (r = 0.763, P = 0.002) and negatively with percentage parenteral energy requirement (r = -0.716, P = 0.006). CONCLUSIONS: In pediatric IF, serum GLP-2 levels increase in patients with small bowel-colic continuity proportionally to the length of resected small intestine. Increase in serum GLP-1 and GLP-2 levels paralleled reducing requirement for parenteral support. These findings support regulation of intestinal adaption by GLP-2 and GLP-1 in children with IF. PMID- 27663541 TI - Caffeine alters glutamate-aspartate transporter function and expression in rat retina. AB - l-Glutamate and l-aspartate are the main excitatory amino acids (EAAs) in the Central Nervous System (CNS) and their uptake regulation is critical for the maintenance of the excitatory balance. Excitatory amino acid transporters (EAATs) are widely distributed among central neurons and glial cells. GLAST and GLT1 are expressed in glial cells, whereas excitatory amino acid transporter 3/excitatory amino acid carrier 1 (EAAT3/EAAC1) is neuronal. Different signaling pathways regulate glutamate uptake by modifying the activity and expression of EAATs. In the present work we show that immature postnatal day 3 (PN3) rat retinas challenged by l-glutamate release [3H]-d-Aspartate linked to the reverse transport, with participation of NMDA, but not of non-NMDA receptors. The amount of [3H]-d-Aspartate released by l-glutamate is reduced during retinal development. Moreover, immature retinae at PN3 and PN7, but not PN14, exposed to a single dose of 200 or 500MUM caffeine or the selective A2A receptor (A2AR) antagonist 100nM ZM241385 decreased [3H]-d-Aspartate uptake. Caffeine also selectively increased total expression of EAAT3 at PN7 and its expression in membrane fractions. However, both EAAT1 and EAAT2 were reduced after caffeine treatment in P2 fraction. Addition of 100nM DPCPX, an A1 receptor (A1R) antagonist, had no effect on the [3H]-d-Aspartate uptake. [3H]-d-Aspartate release was dependent on both extracellular sodium and Dl-TBOA, but not calcium, implying a transporter-mediated mechanism. Our results suggest that in the developing rat retina caffeine modulates [3H]-d-Aspartate uptake by blocking adenosine A2AR. PMID- 27663543 TI - Assessing the relationship between a body shape index and mortality in a group of middle-aged men. AB - BACKGROUND & AIMS: Recently, a new anthropometric parameter emerged, namely A Body Shape Index (ABSI), which appears to be a major risk factor for mortality in the American and British populations. To the best of our knowledge, the relationship between ABSI and mortality was not studied previously in the middle aged Chinese men. Therefore, we assessed the relationship based on a 15-year prospective study. METHODS: In an urban community of Chengdu, 780 middle-aged Chinese men were included in 1992 and followed up for 15 years. RESULTS: During the follow-up, 29 subjects died (mortality rate: 3.7%), and ABSI tended to be linearly associated with mortality. The subjects could be categorized into five groups by the quintiles of baseline ABSI, as follows: the first quintile (Q1), the second quintile (Q2), the third quintile (Q3), the fourth quintile (Q4) and the fifth quintile (Q5). Across the quintiles, the mortality rates were 3.8%, 5.3%, 3.0%, 4.7% and 1.9% in Q1, Q2, Q3, Q4 and Q5, respectively (ptrend = 0.386). With the highest quintile (Q5) as reference, univariate and multivariate Cox regression analyses presented that ABSI was not associated with mortality. CONCLUSIONS: ABSI, a new anthropometric parameter, might not be associated with mortality in the middle-aged Chinese men. Further studies are needed to explore the specificities of ABSI in different populations. PMID- 27663544 TI - Modulation of microRNAs by curcumin in pancreatic cancer. PMID- 27663545 TI - Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives. AB - Subtype-selective alpha1-adrenoceptor (AR) antagonists display optimum therapeutic efficacies for the treatment of benign prostatic hyperplasia (BPH). In this study, we designed and synthesized novel carbazole-arylpiperazines derivatives (1 and 2) on the basis of the proposed pharmacophore model for alpha1 AR antagonists. Structural properties were investigated using single-crystal X ray diffraction analysis. Comparison of crystal structures with ligand-based pharmacophore models revealed that the two agents may possess antagonistic effects on alpha1D subtype. Tissue functional assay in vitro showed that compound 2 exerted strong antagonistic activity on alpha1B-AR (pA2 7.13) with a poor selectivity for alpha1A and alpha1D subtypes. Compound 1 exhibited enhanced antagonistic effect on alpha1D subtype (pA2 7.06) and excellent selectivity for alpha1D over alpha1B (alpha1D/alpha1B ratio=79.4). To illustrate the relationship between antagonistic activity and chemical structure, molecular docking studies were performed using the homology models of alpha1 receptors. Binding mechanism indicated that small hydrophobic substituents attached to the arylpiperazine moiety were essential for rational design of alpha1D-selective antagonists. PMID- 27663546 TI - Analysis of quinolinequinone reactivity, cytotoxicity, and anti-HIV-1 properties. AB - We have analyzed a set of quinolinequinones with respect to their reactivities, cytotoxicities, and anti-HIV-1 properties. Most of the quinolinequinones were reactive with glutathione, and several acted as sulfhydryl crosslinking agents. Quinolinequinones inhibited binding of the HIV-1 matrix protein to RNA to varying degrees, and several quinolinequinones showed the capacity to crosslink HIV-1 matrix proteins in vitro, and HIV-1 structural proteins in virus particles. Cytotoxicity assays yielded quinolinequinone CC50 values in the low micromolar range, reducing the potential therapeutic value of these compounds. However, one compound, 6,7-dichloro-5,8-quinolinequinone potently inactivated HIV-1, suggesting that quinolinequinones may prove useful in the preparation of inactivated virus vaccines or for other virucidal purposes. PMID- 27663547 TI - Thioflavones as novel neuroprotective agents. AB - Oxidative stress is associated with the pathology of neurodegenerative diseases. Identification of small molecules capable of protecting against oxidative stress is therefore of significant importance. In this context, a library of 76 hydroxy flavones, methoxy flavones and their 4-thio analogues has been evaluated for neuroprotection against H2O2-induced oxidative stress. This revealed the synthetic 7,8-dihydroxy 4-thioflavones as neuroprotective compounds, with 14d and 18d showing highest neuroprotective effects at lower concentrations (0.3MUM). Neuroprotection was found to be mediated via activation of the anti-apoptotic cell survival proteins of the ERK1/2 and PI3K/Akt pathways. Structure-activity relationship analysis revealed the B-ring phenyl group as essential for greater neuroprotection. Replacing the 4-CO moiety with a 4-CS moiety also generally enhanced neuroprotection. PMID- 27663548 TI - Design, synthesis, and structure-activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element. AB - Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazole/tetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50 (FXa) value of 0.15MUM and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor. PMID- 27663549 TI - Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents. AB - In an effort to develop novel antimicrobial agents against drug-resistant bacterial infections, 5,6-dihydroimidazo[2,1-b]thiazole compounds were synthesized and tested for their antimicrobial activity. Eight compounds comprised by two sub-scaffolds were identified as hits against methicillin resistant Staphylococcus aureus (MRSA). These hits were modified at 6-position by replacing (S)-6 to (R)-6 configuration and the (R)-isomers increased their antimicrobial activities by two-fold. The most active compound showed a MIC90 value of 3.7MUg/mL against MRSA in a standard microdilution bacterial growth inhibitory assay. This compound protected wax moth worms against MRSA at a dose of 5* MIC using a worm infectious model. This compound also exhibited inhibition of DNA gyrase activity in a DNA gyrase supercoil assay, suggesting the 5,6 dihydroimidazo[2,1-b]thiazoles may target DNA gyrase for the antimicrobial action. PMID- 27663550 TI - Improving properties of Hanji by coating chitosan-silver nanoparticle solution. AB - A chitosan-silver nanoparticle solution (CSNS) was applied as a coating material to Hanji (Korean traditional paper), and the properties of the coated paper were investigated as a function of the dilution ratio. The required CSNS was first prepared from AgNO3 (30mmol) by utilizing chitosan as a reducing and stabilizing agent via ultrasonication. The as-prepared CSNS was diluted to various ratios (undiluted, 1/10, 1/100, and 1/1000) and applied to Hanji by a dip-coating method. The tensile, burst, oil resistance, and antibacterial properties of the coated Hanji against Escherichia coli were evaluated. Among the various dilution ratios, the maximum level of dilution that can positively influence the tensile, burst, oil resistance, and antibacterial properties of Hanji was identified as 1/10, 1/100, 1/10 and 1/1000 of the pure CSNS, respectively. These findings are significant because a specific property of Hanji can be economically improved by changing the dilution ratio. PMID- 27663551 TI - Stimuli-sensitive hollow spheres from chitosan-graft-beta-cyclodextrin for controlled drug release. AB - In this paper, sensitive polymeric hollow spheres self-assembled from chitosan grafted-beta-cyclodextrin (CS-g-CD) and sodium tripolyphosphate (TPP) were prepared for controlled release of doxorubicin (DOX). The assemblies were formed by electrostatic interactions between positively charged amino group in CS-g-CD and negatively charged phosphate in TPP. The hollow spheres with diameters about 100nm were confirmed by transmission electron microscopy (TEM) and laser particle analyzer. The microspheres with hollow cavity were beneficial to improve the drug loading capacity for DOX with entrapment efficiency above 60%. The cumulative release of DOX from CS-g-CD/TPP hollow microspheres increased with the decrease of pH and the increase of temperature or ionic strength. At 37 degrees C and pH 5.2, the maximum drug release was above 90% with a continuous release rate. In vitro cytotoxicity tests indicate that drug loaded hollow spheres exhibited evidently inhibition against cancer cells. These sensitive polymeric hollow spheres are expected to be used in biomedical field as potential carrier. PMID- 27663552 TI - Cross-linked chitosan/sepiolite composite for the adsorption of methylene blue and reactive orange 16. AB - Cross-linked chitosan/sepiolite composite was prepared from sepiolite clay and chitosan, and was cross-linked using epichlorohydrin. Among the various weight ratio percentage of chitosan and sepiolite clay composites, CS50SP50 was selected as the best adsorbent for both methylene blue (MB) and reactive orange 16 (RO 16). At an optimum adsorbent dosage of 0.2g/100mL, the effects of initial dye concentration (25-400mg/L) and pH (3-11) on MB and RO 16 adsorption onto CS50SP50 composite were studied. Monolayer adsorption capacities of CS50SP50 composite for MB and RO 16 were 40.986mg/g and 190.965mg/g, respectively at 30 degrees C. Freundlich, Langmuir and Temkin isotherms applied on the adsorption data for both the dyes reveal that data fitted best for Freundlich model. For both the dyes pseudo-second-order kinetics were found to describe the adsorption process better than pseudo-first-order kinetics. The adsorption capacity of CS50SP50 composite for both the dyes was found better compared to previous studies thus making it potentially low-cost adsorbent for removal of both cationic and reactive dyes. PMID- 27663553 TI - Communicating about cigarette smoke constituents: an experimental comparison of two messaging strategies. AB - Federal law now requires FDA to disseminate information on chemicals in cigarette smoke, but it is unclear how best to do so. In a 2 * 2 between-subjects experiment, participants received a message about chemicals in cigarette smoke (e.g., "Cigarette smoke has benzene.") along with an additional randomly assigned messaging strategy: a "found-in" (e.g., "This is found in gasoline."), a health effect (e.g., "This causes heart disease."), both, or neither. Participants were U.S. probability phone samples of 5000 adults and 1123 adolescents, and an online convenience sample of 4130 adults. Adding a health effect elicited greater discouragement from wanting to smoke cigarettes (all p < .05) as did adding a found-in (all p < .05). However, including both messaging strategies added little or nothing above including just one. These findings can help the FDA and other agencies develop effective and parsimonious messages about cigarette smoke constituents. PMID- 27663554 TI - A test of the first course (Emergency Medicine) that is globally available for credit and for free. AB - BACKGROUND: The WHO has called for the use of computer-aided education to train millions of additional health providers. We herein address this appeal with the first globally available, free, accredited, computer-aided, and peer and mentor guided course. METHODS: The intervention studied was NextGenU.org's first course, "Emergency Medicine (EM) for Senior Medical Students", required for the graduating Classes of 2013 at the University of Missouri (UM) and the U.S. Uniformed Services University of the Health Sciences (USUHS). Control groups were the Class of 2012 at USUHS, and students nationally in the Class of 2013. RESULTS: As of July 2016, there were over 4,000 registered "NextGenUsers" in 145 countries. USUHS NextGenUsers (n=167) averaged 80.3% vs. USUHS control students' 80.9% (n=163, p=0.4) on the Society of Academic EM (SAEM) exam, vs. 71.4% nationally (n=415, p<0.0001). UM NextGenUsers (n=35) averaged 71.2% on the SAEM exam vs. 71.4% nationally (n=415, p=0.8). Both EM Clerkship Directors reported good student satisfaction with these asynchronous, competency-based, site agnostic readings. CONCLUSIONS: This novel model of a free, accredited course is becoming widely used, and has performed as well as some of the world's most resourced courses. PMID- 27663555 TI - Successful carbon dioxide angiography guided endovascular thrombectomy of the superficial femoral artery in a young patient with critical limb ischemia. AB - Currently, the treatment of thromboembolic ischemia of the lower extremities includes percutaneous rotational thrombectomy and aspiration devices. However, the standard approach for endovascular treatment requires the administration of iodine contrast agents, which is problematic in patients with pre-existing renal disease and diabetes. Herein, we describe a case of a CO2 angiography guided endovascular thrombectomy of the superficial femoral artery (SFA) in a young patient with critical limb ischemia. Mechanical thrombectomy using the Rotarex system, catheter aided aspiration and subsequent stent placement in the SFA was entirely guided using CO2 angiography. PMID- 27663557 TI - Traumatic basilar artery entrapment with patency of pontine perforators and absence of significant brainstem infarction: report of an unusual case. AB - We report a rare case of entrapment of the basilar artery into the sphenoid bone caused by a longitudinal fracture of the clivus. Using high resolution three dimensional flat panel angiography, we show preservation of the basilar artery perforators in spite of severe stenosis of the entrapped segment of the basilar artery. There were no obvious signs and symptoms of posterior fossa stroke clinically or radiographically as far as could be assessed under given clinical circumstances. PMID- 27663556 TI - Gas-Phase Analysis of the Complex of Fibroblast GrowthFactor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study. AB - Fibroblast growth factors (FGFs) regulate several cellular developmental processes by interacting with cell surface heparan proteoglycans and transmembrane cell surface receptors (FGFR). The interaction of FGF with heparan sulfate (HS) is known to induce protein oligomerization, increase the affinity of FGF towards its receptor FGFR, promoting the formation of the HS-FGF-FGFR signaling complex. Although the role of HS in the signaling pathways is well recognized, the details of FGF oligomerization and formation of the ternary signaling complex are still not clear, with several conflicting models proposed in literature. Here, we examine the effect of size and sulfation pattern of HS upon FGF1 oligomerization, binding stoichiometry and conformational stability, through a combination of ion mobility (IM) and theoretical modeling approaches. Ion mobility-mass spectrometry (IMMS) of FGF1 in the presence of several HS fragments ranging from tetrasaccharide (dp4) to dodecasaccharide (dp12) in length was performed. A comparison of the binding stoichiometry of variably sulfated dp4 HS to FGF1 confirmed the significance of the previously known high-affinity binding motif in FGF1 dimerization, and demonstrated that certain tetrasaccharide length fragments are also capable of inducing dimerization of FGF1. The degree of oligomerization was found to increase in the presence of dp12 HS, and a general lack of specificity for longer HS was observed. Additionally, collision cross sections (CCSs) of several FGF1-HS complexes were calculated, and were found to be in close agreement with experimental results. Based on the (CCSs) a number of plausible binding modes of 2:1 and 3:1 FGF1-HS are proposed. Graphical Abstract ?. PMID- 27663558 TI - Stroke prevention by endovascular treatment of carotid and vertebral artery dissections. AB - INTRODUCTION: Endovascular intervention for cervical carotid artery dissection (CAD) and vertebral artery dissection (VAD) may be indicated in specific circumstances. OBJECTIVE: To review our institutional experience with endovascular treatment of cervical dissections over the past 20 years to examine indications for treatment, interventional methods, and outcomes. METHODS: Retrospective review of a prospectively maintained database to identify patients with extracranial dissection who underwent endovascular intervention between January 1996 and January 2016. Demographic data and details of procedures, outcomes, and complications were extracted. RESULTS: Of 116 patients [93 CAD, 23 VAD; mean age 44.9 years (range 5-76 years)], 104 underwent stent placement; 11, coil occlusion of the parent artery; and 1, stenting with contralateral vessel occlusion. The cohorts were well matched for age, sex, dissection etiology, and admission and follow-up modified Rankin Scale (mRS) scores. Patients with CAD had significantly more stent placements (p<0.001), failure of medical therapy (p=0.004), and interventions for enlarging pseudoaneurysms (p=0.01) or thromboembolic events (p=0.004). Patients with VAD had significantly more interventions for traumatic occlusion with recanalization (p<0.001). Dissections were spontaneous (n=67), traumatic (n=36), or iatrogenic (n=13). Traumatic dissections in patients with CAD were associated with poor admission mRS scores (p=0.01). Six of 67 (9.0%) patients with spontaneous dissection reported recent chiropractic manipulation. Mean follow-up was 3.5 years (range 1-146 months). Permanent morbidity/mortality was 3.4%, including two deaths. Over a follow-up period of 364 patient-years, 1 stroke occurred (0.27% per year). At last follow up, 41 previously disabled patients [CAD, 31/93 (33.3%); VAD, 10/23 (43.5%)] were no longer disabled; no patient reported worsened disability. CONCLUSIONS: Patients with CAD and VAD differ significantly in presentation, indications for treatment, and treatment methods. Endovascular treatment of CAD and VAD has low procedural morbidity and is associated with a low incidence of future stroke. PMID- 27663559 TI - CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke. AB - BACKGROUND: Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy. METHODS: Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals. RESULTS: Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0-2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS <=2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS <=3 was considered an acceptable outcome. CONCLUSIONS: CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals. PMID- 27663560 TI - The effect of pathologic venous valve on neighboring valves: fluid-structure interactions modeling. AB - Understanding the hemodynamics surrounding the venous valve environment is of a great importance for prosthetic valves design. The present study aims to evaluate the effect of leaflets' stiffening process on the venous valve hemodynamics, valve's failure on the next proximal valve hemodynamics and valve's failure in a secondary daughter vein on the healthy valve hemodynamics in the main vein when both of these valves are distal to a venous junction. Fully coupled, two-way fluid-structure interaction computational models were developed and employed. The sinus pocket region experiences the lowest fluid shear stress, and the base region of the sinus side of the leaflet experiences the highest tissue stress. The leaflets' stiffening increases the tissue stress the valve is experiencing in a very low fluid shear region. A similar effect occurs with the proximal healthy valve as a consequence of the distal valve's failure and with the mother vein valve as a consequence of daughter vein valve's failure. Understanding the described mechanisms may be helpful for elucidating the venous valve stiffness function relationship in nature, the reasons for a retrograde development of reflux and the relationship between venous valves located near venous junctions, and for designing better prosthetic valves and for improving their positioning. PMID- 27663561 TI - Pharmacists' guide to the management of organ donors after brain death. AB - PURPOSE: This article reviews organ donor pathophysiology as it relates to medication use with the goal of maximizing the successful procurement and transplantation of donor organs. SUMMARY: The number of patients requiring organ transplantation continues to grow, yet organ donation rates remain flat, making it critical to appropriately manage each organ donor in order to ensure viability of all transplantable organs. The care given to one organ donor is tantamount to the care of several transplant recipients. Aggressive donor management ensures that the largest number of organs can be successfully procured and improves the organs' overall quality. Hospital pharmacists are responsible for processing orders and preparing the medications outlined in donor management algorithms developed by their respective medical systems. It is important that pharmacists understand the details of the medications used in these protocols in order to critically evaluate each medication order and appropriately manage the donor. Typical medications used in organ donors after brain death include medications for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions. CONCLUSION: It is essential to provide optimal pharmacotherapy for each organ donor to ensure organ recovery and donation. Typical medications used in organ donors include agents for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions. PMID- 27663562 TI - Expanding care through a layered learning practice model. AB - PURPOSE: The outcomes of a patient-centered layered learning practice model (LLPM) in which the clinical specialist acted as the attending pharmacist and managed a pharmacy team to provide direct patient care were evaluated. METHODS: Two 30-day evaluations were conducted on the acute care malignant hematology and medical oncology services of the University of North Carolina Medical Center in 2011. The primary objective of this study was to design an LLPM that used a team to expand the pharmacist care services offered. The primary outcome was the frequency of pharmacy team encounters at discharge (medication reconciliation and counseling), termed the discharge capture rate. RESULTS: During the study months, 42 and 78 malignant hematology and medical oncology patients were eligible for study inclusion, respectively. The overall discharge capture rate was 51%. Sixty one patients received discharge medication reconciliation services during patient counseling. Patients included in the malignant hematology group received a mean of 11 prescriptions at discharge, compared with 9.83 in the medical oncology group. Means of 1.26 and 2.1 medication-related problems per patient were identified in the malignant hematology and medical oncology studies, respectively, during discharge medication reconciliation. The overall mean face time spent per patient was 21.3 minutes. CONCLUSION: Patients in malignant hematology and medical oncology services were counseled and provided discharge medication reconciliation by a pharmacy student or resident whose activities were managed and reviewed by an attending pharmacist using an LLPM, resulting in an improvement in all clinical outcomes and measures. PMID- 27663563 TI - Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag. AB - Recombinant tau protein is widely used to study the biochemical, cellular and pathological aspects of tauopathies, including Alzheimer's disease and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTPD-17). Pure tau in high yield is a requirement for in vitro evaluation of the protein's physiological and toxic functions. However, the preparation of recombinant tau is complicated by the protein's propensity to aggregate and form truncation products, necessitating the use of multiple, time-consuming purification methods. In this study, we investigated parameters that influence the expression of wild type and FTPD-17 pathogenic tau, in an attempt to identify ways to maximise expression yield. Here, we report on the influence of the choice of host strain, induction temperature, duration of induction, and media supplementation with glucose on tau expression in Escherichia coli. We also describe a straightforward process to purify the expressed tau proteins using immobilised metal affinity chromatography, with favourable yields over previous reports. An advantage of the described method is that it enables high yield production of functional oligomeric and monomeric tau, both of which can be used to study the biochemical, physiological and toxic properties of the protein. PMID- 27663565 TI - Initial Treatment of Unresectable Neuroendocrine Tumor Liver Metastases with Transarterial Chemoembolization using Streptozotocin: A 20-Year Experience. AB - BACKGROUND: The majority of patients with neuroendocrine tumor liver metastases (NELM) present with multifocal disease and are not surgical candidates. We present our 20-year experience with transarterial chemoembolization (TACE) using streptozotocin (STZ) in patients with initially unresectable NELM. METHODS: Patients with unresectable NELM treated with TACE using STZ at a single institution from 1995 to 2015 were identified after institutional board approval. Imaging was independently reviewed by a radiologist to evaluate for RECIST 1.1 responses. RESULTS: Ninety-one patients with NELM who underwent 474 TACE treatments during the past 20 years were identified. Median age was 62 years, and 54 % of the patients were females. Median number of TACE treatments per patient was four (range 1-22). TACE treatment with STZ was very well tolerated with 10.3 % of treatments being associated with side effects, predominantly transient, including hyper/hypotension, bradycardia, or postembolization syndrome. Median overall survival from the start of TACE was 44 months (5-year OS from TACE 40.8 % and 5-year PFS 20.3 %), and 54 % of the patients who had carcinoid syndrome reported improved symptoms after TACE treatments. Age, grade, liver tumor burden, and ability to undergo multiple TACE treatments were independent predictors of overall survival in multivariable analysis. Chromogranin A levels >115 ng/ml were associated with worse overall survival (p < 0.001). CONCLUSIONS: In patients with unresectable NELM, TACE with STZ is well tolerated with minimal toxicity and can lead to diminished carcinoid syndrome and long-term survival. This is a novel, conservative approach for the initial treatment of unresectable NELM. PMID- 27663564 TI - How Did We Obtain Complete Remission in Patients Who Had Metastatic Renal Cancer in the Era of Targeted Therapies? AB - BACKGROUND: The management of metastatic renal cell carcinoma (mRCC) has been transformed by the use of targeted therapies, ablative therapies and improved surgical techniques. The objective of this study was to identify therapeutic strategies that resulted in complete remission (CR) and to assess survival of patients in CR. METHODS: In a prospective database, we included all patients treated for mRCC at a university hospital between 2007 and 2015. CR was defined as the absence of metastasis after a full-body computed tomographic scan. RESULTS: We treated 77 patients with mRCC and experienced a CR in 22 (29 %) patients. Patients in CR had, respectively, synchronous and metachronous metastases in 7 (32 %) and 15 (68 %) cases and unique and multiple metastases in 4 (18 %) and 18 (82 %) cases. All patients were treated with cytoreductive nephrectomy and 21 (96 %) had metastasectomy or percutaneous ablation of their metastases. One patient had a CR after systemic treatment with sunitinib. After a median (range) follow-up since metastatic diagnosis of 35 (1-89) months, 12 patients (55 %) had disease recurrence. The median (range) duration of CR before recurrence was 14 (1-39) months. After recurrence, a new CR was obtained in 7 patients (58 %). At the end of follow-up, 16 patients (73 %) were still in CR, 5 (23 %) were undergoing medical treatment, and 1 patient died during the postoperative course. CONCLUSIONS: In the era of targeted-therapies, CRs were obtained with multimodal treatment of metastatic kidney cancer. All patients in CR had a nephrectomy and almost all of them had multiple metastasectomies. PMID- 27663566 TI - Sentinel Lymph Node Genes to Predict Prognosis in Node-Positive Melanoma Patients. AB - PURPOSE: Melanoma patients with a single microscopically-positive sentinel lymph node (SLN) are classified as stage III and are often advised to undergo expensive and substantially toxic adjuvant therapy. However, the 5-year survival rate for these patients, with or without adjuvant therapy, varies from 14 to 85 %, representing a heterogeneous biological population with a variable prognosis. We aimed to identify an SLN gene signature to aid in risk stratification of patients with tumor-positive SLNs. METHODS: Microarray experiments were performed to screen SLN genes in recurrence (N = 39) versus non-recurrence (N = 58) groups in the training dataset. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) assay was applied to confirm the expression of selected SLN genes, which were further verified using an independent validation cohort (N = 30). Area under the receiver operating characteristic curve (AUC) was calculated to evaluate prognostic accuracy of the selected SLN gene panel, and the prognostic value of our SLN gene signature was also compared with the current American Joint Committee on Cancer (AJCC) staging system. RESULTS: We identified two SLN genes (PIGR and TFAP2A) that provided high prognostic accuracy in SLN positive melanoma patients (AUC = 0.864). These two SLN genes, along with clinicopathological features, can differentiate the high- and low-risk groups in node-positive melanoma patients in this cohort. CONCLUSION: The two SLN genes, when combined with clinicopathological features, may offer a new tool for personalized patient risk assessment. PMID- 27663568 TI - Trends in Neoadjuvant Endocrine Therapy Use and Impact on Rates of Breast Conservation in Hormone Receptor-Positive Breast Cancer: A National Cancer Data Base Study. AB - BACKGROUND: The American College of Surgeons Oncology Group Z1031 trial demonstrated that neoadjuvant endocrine therapy (NET) increased breast-conserving surgery (BCS) rates for postmenopausal patients with clinical tumor stage 2-4c estrogen receptor-positive breast cancer. We evaluated national trends in NET use in relation to the conduct of the Z1031 trial and the impact of NET on the rates of BCS. METHODS: Using the National Cancer Data Base (NCDB), we identified all cT2-4c hormone receptor (HR)-positive breast cancer patients age >=50 years from 2004 to 2012. The time intervals of pre-Z1031 (2004-2006), during Z1031 (2007 2009), and post-Z1031 (2010-2012) were examined, and adjusted analyses were performed using multivariable logistic regression. RESULTS: Of 77,272 patients, 2294 (3.0 %) received NET. Clinical T-stage distribution was 66,885 (86.6 %) for cT2, 7318 (9.5 %) for cT3, and 3069 (4.0 %) for cT4a-c. A small but statistically significant increase in NET use was noted, from 2.7 % pre-Z1031 to 3.2 % post Z1031; the adjusted odds ratio (OR) for NET was 1.28 [95 % confidence interval (CI) 1.13-1.45; p < 0.001] for post-Z1031 versus pre-Z1031. NET use varied by clinical T stage, increasing from 1.8 % pre-Z1031 to 2.4 % post-Z1031 in cT2 patients (p < 0.001) and from 6.3 % pre-Z1031 to 7.4 % post-Z1031 in cT3 patients (p = 0.02). Patients receiving NET were more likely to undergo BCS compared with patients undergoing primary surgery (46.4 vs. 43.9 %; p = 0.02) with an adjusted OR of 1.60 (95 % CI 1.46-1.75; p < 0.001). CONCLUSIONS: NET use has increased slowly since the Z1031 trial; however, overall use remains low. NET significantly increased the rates of BCS in patients with HR-positive clinical T2-4c breast cancer. Clinicians should consider NET use for patients with HR-positive breast cancer interested in BCS. PMID- 27663567 TI - Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial. AB - BACKGROUND: Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated. METHODS: In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models were used to evaluate associations between treatment, site of second recurrence, and outcome. RESULTS: The median follow-up period was 4.9 years. Of the 98 patients who received breast-conserving primary surgery 89 had an ipsilateral-breast tumor recurrence. Salvage mastectomy was performed for 73 patients and repeat lumpectomy for 16 patients. Another eight patients had nodal ILRR, and one patient had chest wall ILRR. Among 64 patients whose primary surgery was mastectomy, 52 had chest wall/skin ILRR, and 12 had nodal ILRR. For 15 patients, a second ILRR developed a median of 1.6 years (range 0.08-4.8 years) after ILRR. All second ILRRs occurred for patients with progesterone receptor negative ILRR. Death occurred for 7 (47 %) of 15 patients with a second ILRR and 19 (51 %) of 37 patients with a distant recurrence. As shown in the multivariable analysis, the significant predictors of survival after either a second ILRR or distant recurrence were chemotherapy for the primary cancer (hazard ratio [HR], 3.55; 95 % confidence interval [CI], 1.15-10.9; p = 0.03) and the interval (continuous) from the primary surgery (HR, 0.87; 95 % CI, 0.75-1.00; p = 0.05). CONCLUSIONS: Second ILRRs represented about one third of all recurrence events after ILRR, and all were PR-negative. These second ILRRs and distant metastases portend an unfavorable outcome. PMID- 27663569 TI - Loss of Anti-HER-3 CD4+ T-Helper Type 1 Immunity Occurs in Breast Tumorigenesis and is Negatively Associated with Outcomes. AB - BACKGROUND: We previously demonstrated a progressive loss of the anti-human epidermal growth factor receptor 2 (HER2) CD4+ T-helper type 1 (Th1) response during HER2pos breast tumorigenesis. This loss is associated with residual disease following neoadjuvant therapy and increased risk of recurrence. In this study, we assessed the fate of anti-HER3 Th1 immunity during breast tumorigenesis. METHODS: Peripheral blood from 131 subjects, including healthy donors (HDs), patients with benign breast disease (BD), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC), was collected. Interferon (IFN)-gammapos immune responses to four HER3-derived major histocompatibility complex (MHC) class II promiscuous peptides were tested via enzyme-linked immunosorbent (ELISPOT) assays, and three immune response parameters were compared: anti-HER3 (i) responsivity, or proportion of subjects responding to at least one peptide; (ii) repertoire, or number of responding peptides; and (iii) cumulative response, or summed peptide response. RESULTS: A significant decline in anti-HER3 Th1 response was observed going from HDs to IBC patients; patients with triple negative breast cancer (TNBC) demonstrated the lowest responses. HDs had significantly higher Th1 responses versus estrogen receptor (ER)pos IBC and TNBC patients across all three immune parameters; HER2pos IBC patients displayed responses similar to HDs and BDs. Patients with recurrent breast cancer and residual disease following neoadjuvant therapy demonstrated significantly lower anti-HER3 Th1 immunity compared with patients without recurrence or with a pathologic complete response to neoadjuvant therapy. CONCLUSIONS: Anti-HER3 CD4+ Th1 responses decline during breast tumorigenesis, particularly in TNBC. Attempts to immunologically restore depressed responses in vulnerable subgroups may help mitigate recurrence. PMID- 27663570 TI - Professional Use of Social Media by Pharmacists: A Qualitative Study. AB - BACKGROUND: Social media is frequently used by consumers and health care professionals; however, our knowledge about its use in a professional capacity by pharmacists is limited. OBJECTIVE: Our aim was to investigate the professional use of social media by pharmacists. METHODS: In-depth semistructured interviews were conducted with practicing pharmacists (N=31) from nine countries. Interviews were recorded, transcribed verbatim, and thematically analyzed. RESULTS: Wikipedia, YouTube, and Facebook were the main social media platforms used. Professional use of social media included networking with peers, discussion of health and professional topics, accessing and sharing health and professional information, job searching, and professional promotion. Wikipedia was the participants' first choice when seeking information about unfamiliar topics, or topics that were difficult to search for. Very few pharmacy-related contributions to Wikipedia were reported. YouTube, a video-sharing platform, was used for self education. University lectures, "how-to" footage, and professionally made videos were commonly watched. No professional contribution was made to YouTube. Facebook, a general social networking site, was used for professional networking, promotion of achievements, and job advertisements. It also afforded engagement in professional discussions and information sharing among peers. CONCLUSIONS: Participants used social media in a professional capacity, specifically for accessing and sharing health and professional information among peers. Pharmacists, as medicines experts, should take a leading role in contributing to health information dissemination in these user-friendly virtual environments, to reach not only other health care professionals but also health consumers. PMID- 27663571 TI - Imaging of the thoracic and lumbar spine in a high volume level 1 trauma center: are reformatted images of the spine essential for screening in blunt trauma? AB - Reformatted CTs of the thoracic and lumbar spine (CT T/L) from CTs of the chest, abdomen, and pelvis (CT body) may be performed for screening the thoracolumbar spine in patients sustaining blunt trauma. The purpose of this study was to determine whether there was a difference in the rate of detection of spinal fractures on CTs of the body compared to the reformatted T/L spine. A secondary endpoint was to evaluate whether cases dictated by trainees improved fracture detection rate. We reviewed the records of 250 consecutive blunt trauma patients that received CTs of the chest, abdomen, and pelvis (CT body) with concurrent CT T/L reformats. Each report was reviewed to determine if there was a thoracolumbar fracture and whether a trainee had been involved in interpreting the CT body. If a fracture was identified on either report, then the number, type, and location of each fracture was documented. Sixty-nine fractures, from a total of 38 patients, were identified on either the CT of the body or the CT T/L. Sensitivity for CT body interpretations was 94 % (95 % CI: 86-98 %) compared to a 97 % (95 % CI: 89-100 %) sensitivity for the CT T/L (p > 0.5). Although the sensitivity was 97 % (95 % CI: 88-100 %) when a trainee was involved in interpreting the body CT, there was no statistically significant improvement. The results suggest that with careful scrutiny most spine fractures can be diagnosed on body CT images without the addition of spine reformats. The most commonly missed finding is an isolated non-displaced transverse process fracture, which does not require surgical intervention and does not alter clinical management. The results suggest that thin section reformats do not need to be routinely ordered in screening blunt trauma patients, unless a bony abnormality is identified on the thicker section body CT images. PMID- 27663573 TI - High-flow nasal cannula therapy and apnea time in laryngeal surgery. AB - In small children, high-flow nasal cannula therapy may prolong apnea time even when an inspiratory oxygen fraction below 100% is used. This will be beneficial in prolonged intubation attempts, but especially during procedures requiring prolonged apnea time, leading to fewer airway manipulations and markedly enhanced surgical conditions. PMID- 27663572 TI - Cost Effectiveness of Naloxegol for Opioid-Induced Constipation in the UK. AB - BACKGROUND AND OBJECTIVES: Opioid-induced constipation (OIC) is the most common adverse effect reported in patients receiving opioids to manage pain. Initial treatment with laxatives provides inadequate response in some patients. Naloxegol is a peripherally acting u-opioid receptor antagonist used to treat patients with inadequate response to laxative(s) (laxative inadequate responder [LIR]). A cost effectiveness model was constructed from the UK payer perspective to compare oral naloxegol 25 mg with placebo in non-cancer LIR patients receiving opioids for chronic pain, and a scenario analysis of naloxegol 25 mg with rescue laxatives compared with placebo with rescue laxatives in the same patient population. METHODS: The model comprised a decision tree for the first 4 weeks of treatment, followed by a Markov model with a 4-week cycle length and the following states: 'OIC', 'non-OIC (on treatment)', 'non-OIC (untreated)' and 'death'. Two phase III trials with a follow-up period of 12 weeks provided data on treatment efficacy, transition probabilities, adverse event frequency and patient utility. Resource utilisation data were sourced from a UK-based burden of illness study and physician surveys. A UK National Health Service and Personal Social Service perspective was adopted; costs and health-related quality of life gains were discounted at a rate of 3.5 %. The model was run over a time horizon of 5 years, reflecting the average period of opioid use. RESULTS: Naloxegol has an incremental cost-effectiveness ratio of L10,849 per quality-adjusted life-year gained versus placebo, and L11,179 when rescue laxatives are made available in both arms (2014 values). Model outcomes were only sensitive to variations in utility inputs. However, the probabilistic sensitivity analyses indicate that naloxegol has a 91 % probability of being cost effective at a L20,000 threshold when compared with placebo. CONCLUSIONS: Naloxegol is likely a cost-effective treatment option for LIR patients with OIC. This assessment should be supported by further work on the utility of patients with OIC, including how utility varies with more granular measures of OIC. PMID- 27663574 TI - Individual in Context: The Role of Impulse Control on the Association between the Home, School, and Neighborhood Developmental Contexts and Adolescent Delinquency. AB - Social ecological theories and decades of supporting research suggest that contexts exert a powerful influence on adolescent delinquency. Individual traits, such as impulse control, also pose a developmental disadvantage to adolescents through increasing risk of delinquency. However, such individual differences may also predispose some youth to struggle more in adverse environments, but also to excel in enriched environments. Despite the prominence of impulse control in both developmental and criminological literatures, researchers are only beginning to consider impulse control as an individual characteristic that may affect developmental outcomes in response to environmental input. Using a racially diverse (Latino 46 %; Black 37 %; White 15 %; other race 2 %) sample of 1,216 first-time, male, juvenile offenders from the longitudinal Crossroads Study, this study examined key interactions between baseline impulse control and the home, school, and neighborhood contexts in relation to delinquency within the following 6 months. The results indicated that even after accounting for prior delinquency, youth in more negative home, school, and neighborhood contexts engaged in the same amount of delinquency in the following 6 months regardless of their level of impulse control. However, the effects of positive home, school, and neighborhood contexts on delinquency were stronger for youth with moderate or high impulse control and minimally affected youth with low impulse control. The findings suggest two risk factors for delinquency: low impulse control as a dispositional vulnerability that operates independently of developmental context, and a second that results from a contextual vulnerability. PMID- 27663576 TI - Racial/Ethnic Differences in Perceptions of School Climate and Its Association with Student Engagement and Peer Aggression. AB - Research indicates that a positive school climate is associated with higher levels of student engagement and lower rates of peer aggression. However, less attention has been given to whether such findings are consistent across racial/ethnic groups. The current study examined whether Black, Hispanic, and White high school students differed in their perceptions of school climate, student engagement, and peer aggression as measured by the Authoritative School Climate survey. In addition, the study tested whether the associations between school climate and both student engagement and peer aggression varied as a function of racial/ethnic group. The sample consisted of 48,027 students in grades 9-12 (51.4 % female; 17.9 % Black, 10.5 % Hispanic, 56.7 % White, and 14.9 % other) attending 323 high schools. Regression models that contrasted racial/ethnic groups controlled for the nesting of students within schools and used student covariates of parent education, student gender, and percentage of schoolmates sharing the same race/ethnicity, as well as school covariates of school size and school percentage of students eligible for free- or reduced-price meals. Perceptions of school climate differed between Black and White groups, but not between Hispanic and White groups. However, race/ethnicity did not moderate the associations between school climate and either engagement or peer aggression. Although correlational and cross-sectional in nature, these results are consistent with the conclusion that a positive school climate holds similar benefits of promoting student engagement and reducing victimization experiences across Black, Hispanic, and White groups. PMID- 27663575 TI - Reciprocal Relationships between Teacher Ratings of Internalizing and Externalizing Behaviors in Adolescents with Different Levels of Cognitive Abilities. AB - Are internalizing and externalizing behavior problems interrelated via mutually reinforcing relationships (with each behavior leading to increases over time in levels of the other behavior) or mutually suppressing relationships (with each behavior leading to decreases over time in levels of the other behavior)? Past research on the directionality of these relationships has led to ambiguous results, particularly in adolescence. Furthermore, the extent to which prior results will generalize to adolescents with low levels of cognitive abilities remains unknown. This second limit is particularly important, given that these adolescents are known to present higher levels of externalizing and internalizing behaviors than their peers with average-to-high levels of cognitive abilities, and that the mechanisms involved in the reciprocal relationships between these two types of behaviors may differ across both populations. This study examines the directionality of the longitudinal relationships between externalizing and internalizing behavior problems as rated by teachers across three measurement waves (corresponding to Grades 8-10) in matched samples of 138 adolescents (34.78 % girls) with low levels of cognitive abilities and 556 adolescents (44.88 % girls) with average-to-high levels of cognitive abilities. The results showed that the measurement structure was fully equivalent across time periods and groups of adolescents, revealing high levels of developmental stability in both types of problems, and moderately high levels of cross-sectional associations. Levels of both internalizing and externalizing behaviors were higher among adolescents with low levels of cognitive abilities relative to those with average to-high levels of cognitive abilities. Finally, the predictive analyses revealed negative reciprocal longitudinal relationships (i.e., mutually suppressing relationships) between externalizing and internalizing problems, a result that was replicated within samples of adolescents with low, and average-to-high levels of cognitive ability. PMID- 27663577 TI - A Call for a Science of Engagement: Comment on Rus and Cameron. PMID- 27663579 TI - Relationship between xerostomia and psychotropic drugs in patients with schizophrenia: evaluation using an oral moisture meter. AB - WHAT IS KNOWN AND OBJECTIVE: Patients with schizophrenia are most commonly treated with antipsychotic medications, often with the addition of anxiolytics. This study used an oral moisture meter to evaluate xerostomia in patients with schizophrenia taking typical and atypical antipsychotics, anxiolytics and non psychotropic medications. METHODS: Patients diagnosed with schizophrenia according to ICD-10 criteria in the Department of Psychiatry, Kitasato University East, and affiliated hospitals were studied. All patients were on psychotropic medications. Patients with diseases associated with xerostomia, such as Sjogren's syndrome I, were excluded. RESULTS AND DISCUSSION: A total of 127 patients were enrolled. Mean oral moisture was 27.81 +/- 2.27% (normal, >=30.0%). A significant association was observed between objective oral moisture and the subjective sense of dry mouth. Multivariate analysis revealed a negative correlation between the number of antipsychotics and, especially, anxiolytics, and the degree of oral moisture. Drug dosages themselves were not significantly correlated with dry mouth. These findings suggest that objective oral moisture measurements show decreased moisture in patients on these medications and that the degree of moisture shows a greater negative correlation with the number, as opposed to the dosages, of psychotropic drugs administered. WHAT IS NEW AND CONCLUSIONS: When patients with schizophrenia visit a dental clinic, it is important for the dentist to accurately assess the degree of oral moisture and to determine the medications being taken. Based on these findings of the association of polypharmacy with xerostomia, dentists are encouraged to inform the psychiatrist of the need to actively manage patients' xerostomia. PMID- 27663578 TI - Just-in-Time Adaptive Interventions (JITAIs) in Mobile Health: Key Components and Design Principles for Ongoing Health Behavior Support. AB - Background: The just-in-time adaptive intervention (JITAI) is an intervention design aiming to provide the right type/amount of support, at the right time, by adapting to an individual's changing internal and contextual state. The availability of increasingly powerful mobile and sensing technologies underpins the use of JITAIs to support health behavior, as in such a setting an individual's state can change rapidly, unexpectedly, and in his/her natural environment. Purpose: Despite the increasing use and appeal of JITAIs, a major gap exists between the growing technological capabilities for delivering JITAIs and research on the development and evaluation of these interventions. Many JITAIs have been developed with minimal use of empirical evidence, theory, or accepted treatment guidelines. Here, we take an essential first step towards bridging this gap. Methods: Building on health behavior theories and the extant literature on JITAIs, we clarify the scientific motivation for JITAIs, define their fundamental components, and highlight design principles related to these components. Examples of JITAIs from various domains of health behavior research are used for illustration. Conclusions: As we enter a new era of technological capacity for delivering JITAIs, it is critical that researchers develop sophisticated and nuanced health behavior theories capable of guiding the construction of such interventions. Particular attention has to be given to better understanding the implications of providing timely and ecologically sound support for intervention adherence and retention. PMID- 27663580 TI - What's new in surgical treatment of infective endocarditis? PMID- 27663581 TI - Erratum to: Visit to intensive care of 2050. PMID- 27663582 TI - Amelioration of salvianolic acid C on aortic structure in apolipoprotein E deficient mice treated with angiotension II. AB - AIMS: Aortic aneurysm is a disastrous vascular disease with high morbidity and mortality. Matrix metalloproteinases (MMPs), especially MMP-9, is implicated in the development of aortic aneurysm, but the effective MMP inhibitors are far from development. To develop new candidate compound for aortic aneurysm therapy, we evaluated the effects of salvianolic acid C (SalC) against the formation of aortic aneurysm. MATERIALS AND METHODS: Aortic aneurysm was induced by implantation of angiotension II (AngII) minipump in apolipoprotein E-deficient (ApoE-/-) mice. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. The formation of aortic aneurysm was confirmed based on aortic maximum diameter. Hematoxylin and eosin stain was used to evaluate aortic structure, picrosirius red stain was for collagen deposition, and orcein stain was for elastin fragmentation. Macrophage infiltration was detected by CD68 immunohistochemistry. KEY FINDINGS: Firstly, SalC showed significant inhibition on the activity of MMP-2 and MMP-9. Aortic aneurysm was defined as >50% increase in maximum diameter of aorta, and the down-regulated tendency of 20mg/kg SalC against formation of aortic aneurysm was detected. Also, 22.2% rupture was detected in ApoE-/- mice, while no rupture of aortic aneurysm was found with 20mg/kg SalC treatment. Then, SalC was detected to maintain the integrity of aortic structure and protect elastin against fragmentation. Finally, SalC considerably inhibited infiltration of macrophage in the injury site of aorta. SIGNIFICANCE: SalC significantly ameliorated the progression of aortic aneurysm in ApoE-/- mice, and held great potential for aortic aneurysm therapy. PMID- 27663584 TI - Recognizing the elbow prosthesis on conventional radiographs. AB - The objective of this study was to make an overview that can be useful in determining which type and brand of prosthesis a patient has when visiting the emergency department or outpatient clinic with a periprosthetic fracture, dislocation, or implant failure. The commonly used prostheses in Europe are opted for this list. The radiographs used for this list are obtained either from the company or from our own patients. This list contains the Coonrad/Morrey total elbow prosthesis, the Nexel total elbow prosthesis, the GSB III Elbow Prosthesis, the iBP Total Elbow System, the Discovery Elbow System, the NESimplavit Elbow System, the Latitude Elbow prosthesis, the Solar Elbow, and the Souter Strathclyde total elbow. The characteristics of each prosthesis are described. PMID- 27663583 TI - Brain-Derived Neurotrophic Factor Induces Cell Survival and the Migration of Murine Adult Hippocampal Precursor Cells During Differentiation In Vitro. AB - The generation of new neurons during adulthood involves local precursor cell migration and terminal differentiation in the dentate gyrus. These events are influenced by the hippocampal microenvironment. Brain-derived neurotrophic factor (BDNF) is relevant for hippocampal neuronal development and behavior. Interestingly, studies that have been performed in controlled in vitro systems that involve isolated precursor cells that were derived from the dentate gyrus (AHPCs) have shown that BDNF induces the activation of the TrkB receptor and, consequentially, might activate signaling pathways that favor survival and neuronal differentiation. Based on the fact that the cellular events of AHPCs that are induced by single factors can be studied in this controlled in vitro system, we investigated the ability of BDNF and the involvement of protein kinase C (PKC), as one of the TrkB-downstream activated signaling proteins, in the regulation of migration, here reflected by motility, of AHPCs. Precursor cells were cultured following a concentration-response curve (1-640 ng/ml) for 24 or 96 h. We found that BDNF favored cell survival without altering the viability under culture proliferative conditions of the AHPCs. Concomitantly, glial- and neuronal differentiated precursor cells increased as a consequence of survival promoted by BDNF. Additionally, pharmacological approaches showed that BDNF (40 ng/ml) induced migration of AHPCs was blocked with the compounds K252a and GF109203x, which prevent the activation of TrkB and PKC, respectively. The results indicate that in the in vitro migration of differentiated AHPCs it is involved the BDNF and TrkB cascade. Our results provide additional information about the mechanism by which BDNF impacts adult neurogenesis in the hippocampus. PMID- 27663585 TI - The Change in Facial Emotion Recognition Ability in Inpatients with Treatment Resistant Schizophrenia After Electroconvulsive Therapy. AB - People with schizophrenia have impairments in emotion recognition along with other social cognitive deficits. In the current study, we aimed to investigate the immediate benefits of ECT on facial emotion recognition ability. Thirty-two treatment resistant patients with schizophrenia who have been indicated for ECT enrolled in the study. Facial emotion stimuli were a set of 56 photographs that depicted seven basic emotions: sadness, anger, happiness, disgust, surprise, fear, and neutral faces. The average age of the participants was 33.4 +/- 10.5 years. The rate of recognizing the disgusted facial expression increased significantly after ECT (p < 0.05) and no significant changes were found in the rest of the facial expressions (p > 0.05). After the ECT, the time period of responding to the fear and happy facial expressions were significantly shorter (p < 0.05). Facial emotion recognition ability is an important social cognitive skill for social harmony, proper relation and living independently. At least, the ECT sessions do not seem to affect facial emotion recognition ability negatively and seem to improve identifying disgusted facial emotion which is related with dopamine enriched regions in brain. PMID- 27663586 TI - AZ1366: An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition. AB - Purpose: The emergence of EGFR inhibitors such as gefitinib, erlotinib, and osimertinib has provided novel treatment opportunities in EGFR-driven non-small cell lung cancer (NSCLC). However, most patients with EGFR-driven cancers treated with these inhibitors eventually relapse. Recent efforts have identified the canonical Wnt pathway as a mechanism of protection from EGFR inhibition and that inhibiting tankyrase, a key player in this pathway, is a potential therapeutic strategy for the treatment of EGFR-driven tumors.Experimental Design: We performed a preclinical evaluation of tankyrase inhibitor AZ1366 in combination with multiple EGFR-inhibitors across NSCLC lines, characterizing its antitumor activity, impingement on canonical Wnt signaling, and effects on gene expression. We performed pharmacokinetic and pharmacodynamic profiling of AZ1366 in mice and evaluated its therapeutic activity in an orthotopic NSCLC model.Results: In combination with EGFR inhibitors, AZ1366 synergistically suppressed proliferation of multiple NSCLC lines and amplified global transcriptional changes brought about by EGFR inhibition. Its ability to work synergistically with EGFR inhibition coincided with its ability to modulate the canonical Wnt pathway. Pharmacokinetic and pharmacodynamic profiling of AZ1366-treated orthotopic tumors demonstrated clinically relevant serum drug levels and intratumoral target inhibition. Finally, coadministration of an EGFR inhibitor and AZ1366 provided better tumor control and improved survival for Wnt-responsive lung cancers in an orthotopic mouse model.Conclusions: Tankyrase inhibition is a potent route of tumor control in EGFR-dependent NSCLC with confirmed dependence on canonical Wnt signaling. These data strongly support further evaluation of tankyrase inhibition as a cotreatment strategy with EGFR inhibition in an identifiable subset of EGFR driven NSCLC. Clin Cancer Res; 23(6); 1531-41. (c)2016 AACR. PMID- 27663587 TI - Alternative Lengthening of Telomeres in Primary Pancreatic Neuroendocrine Tumors Is Associated with Aggressive Clinical Behavior and Poor Survival. AB - Purpose: Alternative lengthening of telomeres (ALT), a telomerase-independent telomere maintenance mechanism, is strongly associated with ATRX and DAXX alterations and occurs frequently in pancreatic neuroendocrine tumors (PanNET).Experimental Design: In a Korean cohort of 269 surgically resected primary PanNETs and 19 sporadic microadenomas, ALT status and nuclear ATRX and DAXX protein expression were assessed and compared with clinicopathologic factors.Results: In PanNETs, ALT or loss of ATRX/DAXX nuclear expression was observed in 20.8% and 19.3%, respectively, whereas microadenomas were not altered. ALT-positive PanNETs displayed a significantly higher grade, size, and pT classification (all, P < 0.001). ALT also strongly correlated with lymphovascular (P < 0.001) and perineural invasion (P = 0.001) and the presence of lymph node (P < 0.001) and distant metastases (P = 0.002). Furthermore, patients with ALT-positive primary PanNETs had a shorter recurrence-free survival [HR = 3.38; 95% confidence interval (CI), 1.83-6.27; P < 0.001]. Interestingly, when limiting to patients with distant metastases, those with ALT-positive primary tumors had significantly better overall survival (HR = 0.23; 95% CI, 0.08 0.68; P = 0.008). Similarly, tumors with loss of ATRX/DAXX expression were significantly associated with ALT (P < 0.001), aggressive clinical behavior, and reduced recurrence-free survival (P < 0.001). However, similar to ALT, when limiting to patients with distant metastases, loss of ATRX/DAXX expression was associated with better overall survival (P = 0.003).Conclusions: Both primary ALT positive and ATRX/DAXX-negative PanNETs are independently associated with aggressive clinicopathologic behavior and displayed reduced recurrence-free survival. In contrast, ALT activation and loss of ATRX/DAXX are both associated with better overall survival in patients with metastases. Therefore, these biomarkers may be used as prognostic markers depending on the context of the disease. Clin Cancer Res; 23(6); 1598-606. (c)2016 AACR. PMID- 27663588 TI - Radiological Image Traits Predictive of Cancer Status in Pulmonary Nodules. AB - Purpose: We propose a systematic methodology to quantify incidentally identified pulmonary nodules based on observed radiological traits (semantics) quantified on a point scale and a machine-learning method using these data to predict cancer status.Experimental Design: We investigated 172 patients who had low-dose CT images, with 102 and 70 patients grouped into training and validation cohorts, respectively. On the images, 24 radiological traits were systematically scored and a linear classifier was built to relate the traits to malignant status. The model was formed both with and without size descriptors to remove bias due to nodule size. The multivariate pairs formed on the training set were tested on an independent validation data set to evaluate their performance.Results: The best 4 feature set that included a size measurement (set 1), was short axis, contour, concavity, and texture, which had an area under the receiver operator characteristic curve (AUROC) of 0.88 (accuracy = 81%, sensitivity = 76.2%, specificity = 91.7%). If size measures were excluded, the four best features (set 2) were location, fissure attachment, lobulation, and spiculation, which had an AUROC of 0.83 (accuracy = 73.2%, sensitivity = 73.8%, specificity = 81.7%) in predicting malignancy in primary nodules. The validation test AUROC was 0.8 (accuracy = 74.3%, sensitivity = 66.7%, specificity = 75.6%) and 0.74 (accuracy = 71.4%, sensitivity = 61.9%, specificity = 75.5%) for sets 1 and 2, respectively.Conclusions: Radiological image traits are useful in predicting malignancy in lung nodules. These semantic traits can be used in combination with size-based measures to enhance prediction accuracy and reduce false-positives. Clin Cancer Res; 23(6); 1442-9. (c)2016 AACR. PMID- 27663589 TI - BIRC6 Targeting as Potential Therapy for Advanced, Enzalutamide-Resistant Prostate Cancer. AB - Purpose: Enzalutamide resistance has emerged as a major problem in the management of castration-resistant prostate cancer (CRPC). Research on therapy resistance of CRPCs has primarily focused on the androgen receptor pathway. In contrast, there is limited information on antiapoptotic mechanisms that may facilitate the treatment resistance. The inhibitor of apoptosis proteins (IAP) family is well recognized for its role in promoting treatment resistance of cancers by inhibiting drug-induced apoptosis. Here, we examined whether BIRC6, an IAP family member, has a role in enzalutamide resistance of CRPCs and could provide a therapeutic target for enzalutamide-resistant CRPC.Experimental Design: Use of enzalutamide-resistant CRPC models: (i) the transplantable, first high-fidelity LTL-313BR patient-derived enzalutamide-resistant CRPC tissue xenograft line showing primary enzalutamide resistance, (ii) MR42D and MR49F CRPC cells/xenografts showing acquired enzalutamide resistance. Specific BIRC6 downregulation in these models was produced using a BIRC6-targeting antisense oligonucleotide (ASO-6w2). Gene expression was determined by qRT-PCR and gene expression profiling. Molecular pathways associated with growth inhibition were assessed via gene enrichment analysis.Results: Of eight IAPs examined, BIRC6 was the only one showing elevated expression in both enzalutamide-resistant CRPC models. Treatment with ASO-6w2 markedly suppressed growth of LTL-313BR xenografts and increased tumor apoptosis without inducing major host toxicity. Pathway enrichment analysis indicated that GPCR and matrisome signaling were the most significantly altered pathways. Furthermore, ASO-6w2 inhibited expression of prosurvival genes that were upregulated in the LTL-313BR line.Conclusions:BIRC6 targeting inhibited the growth of enzalutamide-resistant CRPC models and may represent a new option for clinical treatment of advanced, enzalutamide-resistant prostate cancer. Clin Cancer Res; 23(6); 1542-51. (c)2016 AACR. PMID- 27663590 TI - Prognostic Utility of a New mRNA Expression Signature of Gleason Score. AB - PURPOSE: Gleason score strongly predicts prostate cancer mortality; however, scoring varies among pathologists, and many men are diagnosed with intermediate risk Gleason score 7. We previously developed a 157-gene signature for Gleason score using a limited gene panel. Using a new whole-transcriptome expression dataset, we verified the previous signature's performance and developed a new Gleason signature to improve lethal outcome prediction among men with Gleason score 7. EXPERIMENTAL DESIGN: We generated mRNA expression data from prostate tumor tissue from men in the Physicians' Health Study and Health Professionals Follow-Up Study (N = 404) using the Affymetrix Human Gene 1.0 ST microarray. The Prediction Analysis for Microarrays method was used to develop a signature to distinguish high (>=8) versus low (<=6) Gleason score. We evaluated the signature's ability to improve prediction of lethality among men with Gleason score 7, adjusting for 3 + 4/4 + 3 status, by quantifying the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: We identified a 30 gene signature that best distinguished Gleason score <=6 from >=8. The AUC to predict lethal disease among Gleason score 7 men was 0.76 [95% confidence interval (CI), 0.67-0.84] compared with 0.68 (95% CI, 0.59-0.76) using 3 + 4/4 + 3 status alone (P = 0.0001). This signature was a nonsignificant (P = 0.09) improvement over our previous signature (AUC = 0.72). CONCLUSIONS: Our new 30 gene signature improved prediction of lethality among men with Gleason score 7. This signature can potentially become a useful prognostic tool for physicians to improve treatment decision making. Clin Cancer Res; 23(1); 81-87. (c)2016 AACRSee related commentary by Yin et al., p. 6. PMID- 27663591 TI - Co-clinical Assessment of Tumor Cellularity in Pancreatic Cancer. AB - Purpose: Tumor heterogeneity is a hallmark of pancreatic ductal adenocarcinoma (PDAC). It determines tumor biology including tumor cellularity (i.e., amount of neoplastic cells and arrangement into clusters), which is related to the proliferative capacity and differentiation and the degree of desmoplasia among others. Given the close relation of tumor differentiation with differences in progression and therapy response or, e.g., the recently reported protective role of tumor stroma, we aimed at the noninvasive detection of PDAC groups, relevant for future personalized approaches. We hypothesized that histologic differences in PDAC tissue composition are detectable by the noninvasive diffusion weighted- (DW-) MRI-derived apparent diffusion coefficient (ADC) parameter.Experimental design: PDAC cellularity was quantified histologically and correlated with the ADC parameter and survival in genetically engineered mouse models and human patients.Results: Histologic analysis showed an inverse relationship of tumor cellularity and stroma content. Low tumor cellularity correlated with a significantly prolonged mean survival time (PDAClow = 21.93 months vs. PDACmed = 12.7 months; log-rank P < 0.001; HR = 2.23; CI, 1.41-3.53). Multivariate analysis using the Cox regression method confirmed tumor cellularity as an independent prognostic marker (P = 0.034; HR = 1.73; CI, 1.04-2.89). Tumor cellularity showed a strong negative correlation with the ADC parameter in murine (r = -0.84; CI, 0.90- -0.75) and human (r = -0.79; CI, -0.90 to -0.56) PDAC and high preoperative ADC values correlated with prolonged survival (ADChigh = 41.7 months; ADClow = 14.77 months; log rank, P = 0.040) in PDAC patients.Conclusions: This study identifies high tumor cellularity as a negative prognostic factor in PDAC and supports the ADC parameter for the noninvasive identification of PDAC groups. Clin Cancer Res; 23(6); 1461-70. (c)2016 AACR. PMID- 27663592 TI - Selective Targeting of Cyclin E1-Amplified High-Grade Serous Ovarian Cancer by Cyclin-Dependent Kinase 2 and AKT Inhibition. AB - Purpose: Cyclin E1 (CCNE1) amplification is associated with primary treatment resistance and poor outcome in high-grade serous ovarian cancer (HGSC). Here, we explore approaches to target CCNE1-amplified cancers and potential strategies to overcome resistance to targeted agents.Experimental Design: To examine dependency on CDK2 in CCNE1-amplified HGSC, we utilized siRNA and conditional shRNA gene suppression, and chemical inhibition using dinaciclib, a small-molecule CDK2 inhibitor. High-throughput compound screening was used to identify selective synergistic drug combinations, as well as combinations that may overcome drug resistance. An observed relationship between CCNE1 and the AKT pathway was further explored in genomic data from primary tumors, and functional studies in fallopian tube secretory cells.Results: We validate CDK2 as a therapeutic target by demonstrating selective sensitivity to gene suppression. However, we found that dinaciclib did not trigger amplicon-dependent sensitivity in a panel of HGSC cell lines. A high-throughput compound screen identified synergistic combinations in CCNE1-amplified HGSC, including dinaciclib and AKT inhibitors. Analysis of genomic data from TCGA demonstrated coamplification of CCNE1 and AKT2 Overexpression of Cyclin E1 and AKT isoforms, in addition to mutant TP53, imparted malignant characteristics in untransformed fallopian tube secretory cells, the dominant site of origin of HGSC.Conclusions: These findings suggest a specific dependency of CCNE1-amplified tumors for AKT activity, and point to a novel combination of dinaciclib and AKT inhibitors that may selectively target patients with CCNE1-amplified HGSC. Clin Cancer Res; 23(7); 1862-74. (c)2016 AACR. PMID- 27663593 TI - MGD011, A CD19 x CD3 Dual-Affinity Retargeting Bi-specific Molecule Incorporating Extended Circulating Half-life for the Treatment of B-Cell Malignancies. AB - Purpose: CD19, a B-cell lineage-specific marker, is highly represented in B-cell malignancies and an attractive target for therapeutic interventions. MGD011 is a CD19 x CD3 DART bispecific protein designed to redirect T lymphocytes to eliminate CD19-expressing cells. MGD011 has been engineered with a modified human Fc domain for improved pharmacokinetic (PK) properties and designed to cross react with the corresponding antigens in cynomolgus monkeys. Here, we report on the preclinical activity, safety and PK properties of MGD011.Experimental Design: The activity of MGD011 was evaluated in several in vitro and in vivo models. PK, safety and pharmacodynamic activity was also assessed in dose-escalation and repeat-dose studies of MGD011 administered once weekly in cynomolgus monkeys.Results: MGD011 mediated killing of human B-cell lymphoma lines by human or cynomolgus monkey PBMCs as well as autologous B-cell depletion in PBMCs from both species. MGD011-mediated killing was accompanied by target-dependent T-cell activation and expansion, cytokine release and upregulation of perforin and granzyme B. MGD011 demonstrated antitumor activity against localized and disseminated lymphoma xenografts reconstituted with human PBMCs. In cynomolgus monkeys, MGD011 displayed a terminal half-life of 6.7 days; once weekly intravenous infusion of MGD011 at doses up to 100 MUg/kg, the highest dose tested, was well tolerated and resulted in dose-dependent, durable decreases in circulating B cells accompanied by profound reductions of B lymphocytes in lymphoid organs.Conclusions: The preclinical activity, safety and PK profile support clinical investigation of MGD011 as a therapeutic candidate for the treatment of B-cell malignancies. Clin Cancer Res; 23(6); 1506-18. (c)2016 AACR. PMID- 27663595 TI - Bringing Blood-Based Molecular Testing to the Clinic. AB - In cancer, plasma-derived cell-free DNA can be used for detection of oncogenic aberrations relevant for treatment selection. A cell-free DNA-based test for EGFR mutations has been approved as an alternative to tumor tissue analysis in lung cancer. Testing for other aberrations, including copy number alterations, continues to be investigated. Clin Cancer Res; 22(22); 5400-2. (c)2016 AACRSee related article by Chicard et al., p. 5564. PMID- 27663594 TI - Platinum-Based Chemotherapy Induces Methylation Changes in Blood DNA Associated with Overall Survival in Patients with Ovarian Cancer. AB - Purpose: DNA damage repair can lead to epigenetic changes. DNA mismatch repair proteins bind to platinum DNA adducts and at sites of DNA damage can recruit the DNA methylating enzyme DNMT1, resulting in aberrant methylation. We hypothesised that DNA damage repair during platinum-based chemotherapy may cause aberrant DNA methylation in normal tissues of patients such as blood.Experimental Design: We used Illumina 450k methylation arrays and bisulphite pyrosequencing to investigate methylation at presentation and relapse in blood DNA from patients with ovarian cancer enrolled in the SCOTROC1 trial (n = 247) and in a cohort of ovarian tumor DNA samples collected at first relapse (n = 46). We used an ovarian cancer cell line model to investigate the role of the DNA mismatch repair gene MLH1 in platinum-induced methylation changes.Results: Specific CpG methylation changes in blood at relapse are observed following platinum-based chemotherapy and are associated with patient survival, independent of other clinical factors [hazard ratio, 3.7; 95% confidence interval, 1.8-7.6, P = 2.8 * 10-4]. Similar changes occur in ovarian tumors at relapse, also associated with patient survival (hazard ratio, 2.6; 95% confidence interval, 1.0-6.8, P = 0.048). Using an ovarian cancer cell line model, we demonstrate that functional mismatch repair increases the frequency of platinum-induced methylation.Conclusions: DNA methylation in blood at relapse following chemotherapy, and not at presentation, is informative regarding survival of patients with ovarian cancer. Functional DNA mismatch repair increases the frequency of DNA methylation changes induced by platinum. DNA methylation in blood following chemotherapy could provide a noninvasive means of monitoring patients' epigenetic responses to treatment without requiring a tumor biopsy. Clin Cancer Res; 23(9); 2213-22. (c)2016 AACR. PMID- 27663596 TI - How to Deal with Interval-Censored Data Practically while Assessing the Progression-Free Survival: A Step-by-Step Guide Using SAS and R Software. AB - We describe how to estimate progression-free survival while dealing with interval censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution. Clin Cancer Res; 22(23); 5629-35. (c)2016 AACR. PMID- 27663597 TI - Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18F-Fluorodeoxyglucose Positron Emission Tomography. AB - Purpose: The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with 18F-fluorodeoxyglucose (18F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19+ HCC-CSCs can be tracked using 18F-FDG-PET.Experimental Design: K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent 18F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19+/K19- patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter-driven enhanced GFP, 18F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19+/K19- cells.Results: In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19+ cells displayed significantly higher 18F-FDG uptake than K19- cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates 18F-FDG uptake through TGFbeta/Smad signaling, including Sp1 and its downstream target GLUT1.Conclusions:18F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs. Clin Cancer Res; 23(6); 1450-60. (c)2016 AACR. PMID- 27663599 TI - Pharmacokinetically Guided Dosing of Oral Drugs: True Precision Oncology? AB - Higher plasma concentrations of tyrosine kinase inhibitors (TKI), such as pazopanib, are associated with improved clinical outcomes. However, TKI pharmacokinetics exhibit significant interpatient variability, resulting in inconsistent and unpredictable plasma drug levels. An individualized dosing approach based on patient pharmacokinetics data and toxicity can potentially optimize plasma concentrations of pazopanib. Clin Cancer Res; 22(23); 5626-8. (c)2016 AACRSee related article by Verheijen et al., p. 5738. PMID- 27663598 TI - Overexpression of Functional SLC6A3 in Clear Cell Renal Cell Carcinoma. AB - Purpose: Renal cell carcinoma (RCC) is derived from a tissue with a remarkable capacity for vectorial transport. We therefore performed an unbiased exploration of transporter proteins in normal kidney and kidney cancer to discover novel clinical targets.Experimental Design: Using The Cancer Genome Atlas (TCGA) database, we investigated differences in membrane transporter expression in clear cell RCC (ccRCC) and normal kidney. We identified the dopamine transporter SLC6A3 as a specific biomarker for ccRCC. To investigate the functionality of SLC6A3, we used a [3H]-dopamine uptake assay on ccRCC cells. We further explored the effect of hypoxia-inducible factor (HIF) proteins on SLC6A3 expression by introducing siRNA in ccRCC cells and by hypoxic treatment of nonmalignant cells.Results: We show that ccRCC expresses very high transcript levels of SLC6A3 in contrast to normal kidney tissue and other tumor types, which do not express appreciable levels of this transporter. Importantly, we demonstrate that the elevated expression of SLC6A3 in ccRCC cells is associated with specific uptake of dopamine. By targeting the expression of HIF-1alpha and HIF-2alpha, we could show that SLC6A3 expression is primarily influenced by HIF-2alpha and that hypoxia can induce SLC6A3 expression in normal renal cells.Conclusions: We conclude that the dopamine transporter SLC6A3 constitutes a novel biomarker that is highly specific for ccRCC. We further postulate that the protein can be exploited for diagnostic or therapeutic purposes for detection or treatment of ccRCC. Clin Cancer Res; 23(8); 2105-15. (c)2016 AACR. PMID- 27663601 TI - Adjuvant Chemotherapy for Stage II Colon Cancer: Practice Patterns and Effectiveness in the General Population. AB - AIMS: Although guidelines do not recommend adjuvant chemotherapy (ACT) for stage II colon cancer, many state that ACT may be considered in high-risk disease. Here we describe practice patterns and outcomes associated with ACT in the general population. MATERIALS AND METHODS: All cases of colon cancer diagnosed in Ontario 2002-2008 were identified using the Ontario Cancer Registry, which was linked to electronic treatment records. Pathology reports were obtained for a 25% random sample of cases. High-risk disease was defined as: T4 tumours, <12 lymph nodes, poorly differentiated histology, lymphovascular invasion. Modified Poisson regression was used to evaluate factors associated with ACT. The Cox proportional hazards model was used to explore the association between ACT and cancer-specific (CSS) and overall survival. RESULTS: The study population included 2488 patients with stage II colon cancer; 1175 (47%) with high-risk disease. ACT was delivered to 18% of all patients and 24% of patients with high-risk disease. ACT rates were higher among younger patients (51% age 20-49 years versus 16% age 70-79, P < 0.001) and varied considerably across geographic regions (range 10-39%, P < 0.001). Among all patients with stage II colon cancer, ACT was not associated with improved CSS (hazard ratio 1.41, 95% confidence interval 1.09-1.82) or overall survival (hazard ratio 1.16, 95% confidence interval 0.94-1.42). Stratified survival analysis for patients with high-risk disease did not show benefit to ACT (CSS hazard ratio 1.14, 95% confidence interval 0.84-1.55; overall survival hazard ratio 1.02, 95% confidence interval 0.79-1.31). CONCLUSION: ACT use varies across age groups and geographic regions. ACT is not associated with improved survival among patients with stage II colon cancer including those with high-risk disease. PMID- 27663602 TI - Lead Contamination and Source Characterization in Soils Around a Lead-Zinc Smelting Plant in a Near-Urban Environment in Baoji, China. AB - Economic reforms in China since 1978 have promoted nationwide socioeconomic advancement but led to a considerable amount of environmental pollution. The distribution and sources of Pb in a typical peri-urban industrial part of Baoji, China, were assessed by determining the Pb contents and isotopic compositions in 52 topsoil samples from the study area. The topsoil samples were polluted averagely with 40.88 mg Pb kg-1, was 1.86 times higher than the Pb content of local background soil (22.04 mg kg-1). Pb isotopic compositions were determined by analyzing samples prepared using total digestion and acid extraction methods. Radiogenic isotopes contributed more to the Pb concentrations in the acid extracts than in the total digests. This was shown by the 207/206Pb and 208/206Pb ratios, which were 0.845-0.88 and 2.088-2.128, respectively, in the acid extracts and 0.841-0.875 and 2.086-2.125, respectively, in the total digests. This indicates that anthropogenic sources of Pb could be identified more sensitively in acid extracts than in total digests. The Pb isotope ratios showed that burning coal and smelting ore are the predominant anthropogenic sources of Pb in the study area, i.e., a lead-zinc smelter and a coking plant are major sources of Pb in the study area. PMID- 27663600 TI - Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer. AB - Purpose: Our preclinical studies showed that the PARP inhibitor, olaparib, prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence specific pharmacokinetic and pharmacodynamic effects, safety, and activity of the combination.Experimental Design: Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200 mg twice daily, days 1-7) in a 3 + 3 dose escalation with carboplatin AUC4 or 5 every 21 days, up to eight cycles, followed by olaparib 300 mg twice daily maintenance. Patients were randomly assigned to starting schedule: cohort A (olaparib days 1-7, carboplatin on day 8) or B (carboplatin on day 1, olaparib days 2-8) during cycle 1. Patients received the reversed scheme in cycle 2. Blood was collected for olaparib pharmacokinetics, platinum-DNA adducts, comet assay, and PAR concentrations. The primary objectives were to examine schedule-dependent effects on olaparib pharmacokinetics and platinum-DNA adducts.Results: A total of 77 (60 ovarian, 14 breast, and 3 uterine cancer) patients were treated. Dose-limiting toxicity was thrombocytopenia and neutropenia, defining olaparib 200 mg twice daily + carboplatin AUC4 as the MTD. Olaparib clearance was increased approximately 50% when carboplatin was given 24 hours before olaparib. In vitro experiments demonstrated carboplatin preexposure increased olaparib clearance due to intracellular olaparib uptake. Quantities of platinum-DNA adducts were not different as a function of the order of drug administration. Responses included 2 CRs and 31 PRs (46%) with a higher RR in BRCA mutation carriers compared with nonmutation carriers (68% vs. 19%).Conclusions: Tablet olaparib with carboplatin is a safe and active combination. Carboplatin preexposure causes intracellular olaparib accumulation reducing bioavailable olaparib, suggesting carboplatin should be administered prior to olaparib. Clin Cancer Res; 23(6); 1397-406. (c)2016 AACR. PMID- 27663603 TI - Wilms tumor accompanied by premature chromatid separation. PMID- 27663605 TI - Levodopa Effect on Basal Ganglia Motor Circuit in Parkinson's Disease. AB - AIMS: To investigate the effects of levodopa on the basal ganglia motor circuit (BGMC) in Parkinson's disease (PD). METHODS: Thirty PD patients with asymmetrical bradykinesia and 30 control subjects were scanned using resting-state functional MRI. Functional connectivity of the BGMC was measured and compared before and after levodopa administration in patients with PD. The correlation between improvements in bradykinesia and changes in BGMC connectivity was examined. RESULTS: In the PD-off state (before medication), the posterior putamen and internal globus pallidus (GPi) had decreased connectivity while the subthalamic nucleus (STN) had enhanced connectivity within the BGMC relative to control subjects. Levodopa administration increased the connectivity of posterior putamen and GPi-related networks but decreased the connectivity of STN-related networks. Improvements in bradykinesia were correlated with enhanced connectivity of the posterior putamen-cortical motor pathway and with decreased connectivity of the STN-thalamo-cortical motor pathway. CONCLUSION: In PD patients with asymmetrical bradykinesia, levodopa can partially normalize the connectivity of the BGMC with a larger effect on the more severely affected side. Moreover, the beneficial effect of levodopa on bradykinesia is associated with normalization of the striato-thalamo-cortical motor and STN-cortical motor pathways. Our findings inform the neural mechanism of levodopa treatment in PD. PMID- 27663604 TI - Transjugular Intrahepatic Portosystemic Shunts With Covered Stents Increase Transplant-Free Survival of Patients With Cirrhosis and Recurrent Ascites. AB - BACKGROUND & AIMS: There is controversy over the ability of transjugular intrahepatic portosystemic shunts (TIPS) to increase survival times of patients with cirrhosis and refractory ascites. The high rate of shunt dysfunction with the use of uncovered stents counteracts the benefits of TIPS. We performed a randomized controlled trial to determine the effects of TIPS with stents covered with polytetrafluoroethylene in these patients. METHODS: We performed a prospective study of 62 patients with cirrhosis and at least 2 large-volume paracenteses within a period of at least 3 weeks; the study was performed at 4 tertiary care centers in France from August 2005 through December 2012. Patients were randomly assigned to groups that received covered TIPS (n = 29) or large volume paracenteses and albumin as necessary (LVP+A, n = 33). All patients maintained a low-salt diet and were examined at 1 month after the procedure then every 3 months until 1 year. At each visit, liver disease-related complications, treatment modifications, and clinical and biochemical variables needed to calculate Child-Pugh and Model for End-Stage Liver Disease scores were recorded. Doppler ultrasonography was performed at the start of the study and then at 6 and 12 months after the procedure. The primary study end point was survival without a liver transplant for 1 year after the procedure. RESULTS: A higher proportion of patients in the TIPS group (93%) met the primary end point than in the LVP+A group (52%) (P = .003). The total number of paracenteses was 32 in the TIPS group vs 320 in the LVP+A group. Higher proportions of patients in the LVP+A group had portal hypertension-related bleeding (18% vs 0%; P = .01) or hernia-related complications (18% vs 0%; P = .01) than in the TIPS group. Patients in LVP+A group had twice as many days of hospitalization (35 days) as the TIPS group (17 days) (P = .04). The 1-year probability of remaining free of encephalopathy was 65% for each group. CONCLUSIONS: In a randomized trial, we found covered stents for TIPS to increase the proportion of patients with cirrhosis and recurrent ascites who survive transplantation-free for 1 year, compared with patients given repeated LVP+A. These findings support TIPS as the first-line intervention in such patients. ClinicalTrials.gov ID: NCT00222014. PMID- 27663607 TI - Permanent His-bundle pacing in patients with prosthetic cardiac valves. AB - BACKGROUND: Conduction disease is not uncommon after prosthetic valve (PV) surgery. The feasibility of His-bundle pacing (HBP) in this patient population is not well studied. OBJECTIVE: The purpose of this study was to report our experience with permanent HBP in patients undergoing pacemaker implantation after PV surgery. METHODS: Permanent HBP was attempted in patients with AV conduction disease after PV surgery referred for pacemaker implantation. Conduction disease was characterized as AV nodal vs infranodal. Feasibility, relationship of HBP lead to PVs, and HBP characteristics were recorded. RESULTS: Thirty patients (47% men, age 74 +/- 12 years, left ventricular ejection fraction 49% +/- 11%) with AV conduction disease (100% patients; 14 with infranodal block; right bundle branch block 9, left bundle branch block 5, intraventricular conduction delay 1) underwent HBP. PVs included aortic valve replacement (AVR) in 8 patients (infranodal block 6 patients), tricuspid valve (TV) ring with mitral valve replacement or repair (MVR) in 10 patients (AV nodal block 9 patients), transcatheter aortic valve replacement (TAVR) in 4 patients (infranodal block 4 patients), and MVR alone in 6 patients. HBP was successful in 28 patients (93%) (selective HBP 50%). His bundle (HB) recruitment was unsuccessful in 2 patients with TAVR. AVR/TAVR and TV ring served as anatomic landmarks for localizing the HB. Successful sites of HBP were posterior and inferior to AVR/TAVR and distal and septal to the TV ring. Baseline QRSd improved from 124 +/- 32 ms to 118 +/- 20 ms (P = .39). HBP threshold at implant was 1.45 +/- 1 V at 1 ms. CONCLUSION: Permanent HBP was feasible in 93% of patients with PVs. Patients with AVR/TAVR predominantly developed infranodal block compared to AV nodal block in patients with TV ring/MVR. Location of PV might serve as a landmark for identifying the site of the HB. PMID- 27663606 TI - A novel approach for left ventricular lead placement in cardiac resynchronization therapy: Intraprocedural integration of coronary venous electroanatomic mapping with delayed enhancement cardiac magnetic resonance imaging. AB - BACKGROUND: Placing the left ventricular (LV) lead at a site of late electrical activation remote from scar is desired to improve cardiac resynchronization therapy (CRT) response. OBJECTIVE: The purpose of this study was to integrate coronary venous electroanatomic mapping (EAM) with delayed enhancement cardiac magnetic resonance (DE-CMR) enabling LV lead guidance to the latest activated vein remote from scar. METHODS: Eighteen CRT candidates with focal scar on DE-CMR were prospectively included. DE-CMR images were semi-automatically analyzed. Coronary venous EAM was performed intraprocedurally and integrated with DE-CMR to guide LV lead placement in real time. Image integration accuracy and electrogram parameters were evaluated offline. RESULTS: Integration of EAM and DE-CMR was achieved using 8.9 +/- 2.8 anatomic landmarks and with accuracy of 4.7 +/- 1.1 mm (mean +/- SD). Maximal electrical delay ranged between 72 and 197ms (57%-113% of QRS duration) and was heterogeneously located among individuals. In 12 patients, the latest activated vein was located outside scar, and placing the LV lead in the latest activated vein remote from scar was accomplished in 10 patients and prohibited in 2 patients. In the other 6 patients, the latest activated vein was located in scar, and targeting alternative veins was considered. Unipolar voltages were on average lower in scar compared to nonscar (6.71 +/- 3.45 mV vs 8.18 +/- 4.02 mV [median +/- interquartile range), P <.001) but correlated weakly with DE-CMR scar extent (R -0.161, P <.001) and varied widely among individual patients. CONCLUSION: Integration of coronary venous EAM with DE-CMR can be used during CRT implantation to guide LV lead placement to the latest activated vein remote from scar, possibly improving CRT. PMID- 27663608 TI - Comparative Temporal Expression Analysis of MicroRNAs and Their Target Genes in Contrasting Wheat Genotypes During Osmotic Stress. AB - MicroRNAs (miRNAs) are important nonprotein-coding genes involved in almost all biological processes during biotic and abiotic stresses in plants. To investigate the miRNA-mediated plant response to drought stress, two drought-tolerant (C-306 and NI-5439) and two drought-sensitive (HUW-468 and WL-711) wheat genotypes were exposed to 25 % PEG 6000 for 1, 12 and 24 h. Temporal expression patterns of 12 drought-responsive miRNAs and their corresponding nine targets were monitored by quantitative real-time PCR (qRT-PCR). The results showed differential expression of miRNAs and their targets with varying degree of upregulation and downregulation in drought-sensitive genotypes. Likewise, in drought-tolerant wheat genotypes, maximum accumulation of miR393a and miR397a was observed at 1 h of stress. In addition, nearly perfect negative correlation was observed in four miRNA and target pairs (miR164-NAC, miR168a-AGO, miR398-SOD and miR159a-MYB) across all the temporal period studied which could be a major player during drought response in wheat. We, for the first time, validated the presence of miR529a and miR1029 in wheat. These findings gives a clue for temporal and variety-specific differential regulation of miRNAs and their targets in wheat in response to osmotic shock and could help in defining the potential roles of miRNAs in plant adaptation to osmotic stress in future. PMID- 27663609 TI - Silencing of Target Chitinase Genes via Oral Delivery of dsRNA Caused Lethal Phenotypic Effects in Mythimna separata (Lepidoptera: Noctuidae). AB - Mythimna separata walker (Lepidoptera: Noctuidae) is a polyphagous, migratory corn pest. Outbreak of M. separata has led to severe damage to corn production recently in China. RNAi (RNA interference) is a gene silencing technology applied both in model and non-model organisms, and it is especially useful for the latter in which the reverse genetic research tools are not available. RNAi approach was broadly investigated in many plant pathogens and was used for the generation of anti-pest transgenic plants. We are proposing to use this technology to silence M. separata endogenous genes, thereby, providing a biocontrol method for this insect. Feeding of dsRNAs for target Chitinase genes resulted in substantial decreases of their transcript levels in M. separata. Furthermore, silencing of target Chitinase genes led to phenotypic effects such as reduced body weight and increased mortality. Our study provided both reverse genetic research tool and potential control strategy for this insect species. PMID- 27663610 TI - Is nicotine replacement really ineffective? A reply to Stanley and Massey. PMID- 27663611 TI - Mode of delivery affected questionnaire response rates in a birth cohort study. AB - OBJECTIVES: Cohort studies must collect data from their participants as economically as possible, while maintaining response rates. This randomized controlled trial investigated whether offering a choice of online or paper questionnaires resulted in improved response rates compared with offering online first. STUDY DESIGN AND SETTING: Eligible participants were young people in the Avon Longitudinal Study of Parents and Children (ALSPAC) study (born April 1, 1991, to December 31, 1992, in the Avon area). After exclusions, 8,795 participants were randomized. The "online first" group were invited to complete the questionnaire online. The "choice" group were also sent a paper questionnaire and offered a choice of completion method. The trial was embedded within routine data collection. The main outcome measure was the number of questionnaires returned. Data on costs were also collected. RESULTS: Those in the "online first" arm of the trial were less likely to return a questionnaire [adjusted odds ratio: 0.90; 95% confidence interval (CI): 0.82, 0.99]. The "choice" arm was more expensive (mean difference per participant L0.71; 95% CI: L0.65, L0.76). It cost an extra L47 to have one extra person to complete the questionnaire in the "choice" arm. CONCLUSION: Offering a choice of completion methods (paper or online) for questionnaires in ALSPAC increased response rates but was more expensive than offering online first. PMID- 27663612 TI - A comparative evaluation between aluminium and titanium dioxide microparticles for blasting the surface titanium dental implants: an experimental study in rabbits. AB - OBJECTIVE: The aim of this study was to compare, through biomechanical and histological analysis, the aluminium (AlO2) and titanium dioxide (TiO2) microparticles for blasting during the sandblasting acid surface treatment in titanium dental implants using a rabbit tibia model. MATERIALS AND METHODS: Forty eight commercially available titanium dental implants were divided into two test groups (n = 24 per group): implants with surface treated by AlO2 followed by acid etching as control group (Con group) and implants with surface treated by TiO2 followed by acid etching as test group (Test group). The implants were randomly installed in both tibias of eight rabbits and block samples were removed 4 and 8 weeks after implantation. Resonance Frequency Analyses were performed immediately after the implantation and at 8 weeks. Twelve implants of each group were removed to measure the reverse torque. The remaining implants were used for histological analysis. The data were compared using statistical tests (alpha = 0.05). RESULTS: In comparing the implant stability quotient at the two time points, no significant statistical differences were found (P > 0.05), as well as in the removal torque test at 8 weeks after implant placement, no found significant difference between the two groups was tested. Histomorphometric analysis showed a high degree of bone organization in all samples with no significant difference between groups in the bone-to-implant contact (P > 0.05). CONCLUSION: Within the limitations of this study, the results indicate that the media of surface blasting (AlO2 or TiO2 microparticles) did not show significant differences in the tested parameters for assessing the osseointegration of the implants. PMID- 27663613 TI - One-Year Review of the SCREEN (Skin Cancer Post-Transplant) Clinic. AB - The Skin Cancer Post-Transplant (SCREEN) Clinic is a skin-cancer screening clinic that is fully integrated into the renal transplantation clinic at St Paul's Hospital in Vancouver, British Columbia. The purpose of this review was to determine characteristics of patients most at risk for skin cancer, to specify types and locations of skin cancers diagnosed, and to identify areas for patient and physician education. Transplant patients (91% renal; 5% heart) screened by a dermatologist during a 12-month period were stratified into low-, medium-, and high-risk groups based on detailed history and skin examination. In total, 118 skin cancers were diagnosed. White males were found to be most at risk. Squamous cell carcinoma accounted for the majority of tumours, over 25% of which demonstrated invasion. Forty-two percent of patients used only 1 to 2 bottles of sunscreen per year, and sun-protective practices were limited. With this information, we have identified potential target areas for patient and physician education. PMID- 27663614 TI - How Effective Is Supplemental Intraseptal Anesthesia in Patients with Symptomatic Irreversible Pulpitis? AB - INTRODUCTION: Previous studies have reported high levels of success with intraseptal injection for various dental procedures but provide limited information on the use of the injection during endodontic treatment. Therefore, the purpose of this prospective study was to determine the anesthetic efficacy of the supplemental intraseptal technique in mandibular posterior teeth diagnosed with symptomatic irreversible pulpitis when the conventional inferior alveolar nerve (IAN) block failed. METHODS: One hundred patients with a diagnosis of symptomatic irreversible pulpitis in a mandibular posterior tooth were recruited. Following profound lip numbness after the administration of the conventional IAN block, endodontic treatment was initiated. Patients still experiencing moderate to severe pain during treatment were administered mesial and distal supplemental intraseptal injections using 0.7 mL 4% articaine with 1:000,000 epinephrine administered with a computer-controlled local anesthetic delivery unit. Success was defined as the ability to perform endodontic access and instrumentation with mild to no pain. RESULTS: Success with the IAN block was achieved in 25% of patients. Supplemental intraseptal injections provided success in 29% of patients. CONCLUSIONS: Supplemental intraseptal injections achieved profound pulpal anesthesia in 29% of patients when the IAN block failed. This low level of success would not provide predictable levels of anesthesia for patients requiring emergency endodontic treatment for symptomatic irreversible pulpitis in mandibular posterior teeth. PMID- 27663615 TI - Triple Antibiotic Polymer Nanofibers for Intracanal Drug Delivery: Effects on Dual Species Biofilm and Cell Function. AB - INTRODUCTION: Root canal disinfection and the establishment of an intracanal microenvironment conducive to the proliferation/differentiation of stem cells play a significant role in regenerative endodontics. This study was designed to (1) investigate the antimicrobial efficacy of triple antibiotic-containing nanofibers against a dual-species biofilm and (2) evaluate the ability of dental pulp stem cells (DPSCs) to adhere to and proliferate on dentin upon nanofiber exposure. METHODS: Seven-day-old dual-species biofilm established on dentin specimens was exposed for 3 days to the following: saline (control), antibiotic free nanofibers (control), and triple antibiotic-containing nanofibers or a saturated triple antibiotic paste (TAP) solution (50 mg/mL in phosphate buffer solution). Bacterial viability was assessed using the LIVE/DEAD assay (Molecular Probes, Inc, Eugene, OR) and confocal laser scanning microscopy. For cytocompatibility studies, dentin specimens after nanofiber or TAP (1 g/mL in phosphate buffer solution) exposure were evaluated for cell adhesion and spreading by actin-phalloidin staining. DPSC proliferation was assessed on days 1, 3, and 7. Statistics were performed, and significance was set at the 5% level. RESULTS: Confocal laser scanning microscopy showed significant bacterial death upon antibiotic-containing nanofiber exposure, differing significantly (P < .05) from antibiotic-free fibers and the control (saline). DPSCs showed enhanced adhesion/spreading on dentin specimens treated with antibiotic-containing nanofibers when compared with its TAP counterparts. The DPSC proliferation rate was similar on days 1 and 3 in antibiotic-free nanofibers, triple antibiotic containing nanofibers, and TAP-treated dentin. Proliferation was higher (9-fold) on dentin treated with antibiotic-containing nanofibers on day 7 compared with TAP. CONCLUSIONS: Triple antibiotic-containing polymer nanofibers led to significant bacterial death, whereas they did not affect DPSC attachment and proliferation on dentin. PMID- 27663616 TI - Osteoprotegerin-Knockout Mice Developed Early Onset Root Resorption. AB - INTRODUCTION: Recent studies indicate that the osteoprotegerin (OPG)/RANKL/RANK pathway takes part in root resorption. However, the relationship between OPG and root resorption is vague. The purpose of our study was to investigate the role of OPG in root resorption. METHODS: The first molars of the mandibles of osteoprotegerin-knockout (Opg-KO) mice and wild-type (WT) mice were evaluated by micro-computed tomography, histology, and immunohistochemistry at 4, 6, 26, and 52 weeks. To detect the activity of the osteoclasts, we induced bone marrow macrophages into osteoclast-like cells from Opg-KO mice and wild-type mice in vitro and then compared their osteoclast activities. To evaluate the cementum quality, an osteoclast-cementum co-culture model was established in vitro. RESULTS: In Opg-KO mice, root resorption began at the age of 4 weeks. At 6 weeks the cementum damage extended to the coronal and apical regions, and at 52 weeks the damage reached the predentin. At all observed stages, more tartrate-resistant acid phosphatase (TRAP)-positive cells were found on the surface of cementum in Opg-KO mice. In vitro, the mRNA levels of cathepsin K, TRAP, matrix metalloproteinase-9, and matrix metalloproteinase-1, as well as the protein expression of nuclear factor of activated T cell 1 and TRAP, increased significantly in osteoclast-like cells from Opg-KO mice. In addition, the cementum resorption pits of Opg-KO mice were larger when co-cultured with osteoclast-like cells. CONCLUSIONS: Our study demonstrated that loss of OPG led to root resorption via increasing activation of osteoclasts and reducing mineralization of cementum. PMID- 27663617 TI - Biocompatibility Evaluation of EndoSequence Root Repair Paste in the Connective Tissue of Rats. AB - INTRODUCTION: The aim of this study was to evaluate the subcutaneous connective tissue response to EndoSequence root repair paste (Brasseler, Savannah, GA) compared with mineral trioxide aggregate (MTA). METHODS: Thirty-six Wistar rats each received 3 sterile tubes, containing 1 of the tested materials and control. The animals were killed 1, 3 and 6 weeks after implantation. The specimens were evaluated histologically for type of inflammation, intensity and extent of inflammatory cells, foreign body reaction, fibrous capsule thickness, perivascular fragments, calcific deposits and vascular congestion. RESULTS: EndoSequence provoked severe inflammation after 1 week, which was significantly different from MTA and control (P ? .05), with fragmented particles and foreign body reaction. MTA showed tissue-tolerance features almost comparable to control. CONCLUSIONS: EndoSequence was significantly more irritating than MTA and control at 1 and 3 weeks in terms of severity and extent of inflammation. After 6 weeks it displayed more biocompatible characteristics. PMID- 27663618 TI - Scouting Ability of 4 Pathfinding Instruments in Moderately Curved Molar Canals. AB - INTRODUCTION: Glide path preparation has been recommended as a mandatory clinical step to ensure the safe usage of nickel-titanium (NiTi) rotary instruments. This study aimed to evaluate the effectiveness and fracture rate of 4 pathfinding NiTi rotary instruments in mechanically negotiating moderately curved molar canals. METHODS: Moderately curved maxillary (n = 120) and mandibular (n = 120) molars were randomly distributed into 4 experimental groups (n = 60, 30 maxillary and 30 mandibular molars) according to the instrument used for glide path preparation: ScoutRace 10/.02 (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (800 rpm and 1 Ncm torque), ProDesign 25/.01 (Easy Equipamentos Odontologicos, Belo Horizonte, MG, Brazil) (350 rpm and 1-Ncm torque), Mtwo 10/.04 (VDW, Munich, Germany) (280 rpm and 1.2 Ncm torque), or ProGlider 16/.02 (Dentsply Maillefer, Ballaigues, Switzerland) (300 rpm and 5-Ncm torque). The instrument fracture rate and the absolute and percentage frequencies of molars in which the pathfinding instruments reached the full working length in all root canals according to tooth and canal types were recorded and statistically compared using the Pearson's chi square test (alpha = 5%). RESULTS: The highest and lowest frequency of reached the full working length canals were observed in the ScoutRace (68.3%) and ProDesign (38.3%) groups (P < .05), respectively, whereas the Mtwo (58.3%) and ProGlider (51.6%) groups showed intermediate results (P > .05). The ProGlider group showed the highest percentage frequency of instrument separation (11.6%) followed by the Mtwo (8.3%), ScoutRace (3.3%), and ProDesign (3.3%) groups (P < .05). CONCLUSIONS: ScoutRace performed more efficiently and with less instrument breakage than the other systems. ProDesign was the least efficient, and ProGlider exhibited the highest rate of instrument breakage among the systems tested. PMID- 27663619 TI - Gait abnormalities before and after total hip arthroplasty differ in men and women. AB - This study tested the hypothesis that men and women have different preoperative and postoperative gait impairment relative to sex-matched healthy controls, and that the extent of gait improvement after total hip arthroplasty (THA) is different between men and women. A group of 124 THA subjects was identified from a motion analysis data repository; age and BMI-matched male and female control groups were then identified from the same repository. Dynamic sagittal plane hip range of motion (HROM) and peak 3D external moments at subjects' normal walking speeds were analyzed. Each hypotheses was tested using linear regression models, to adjust for potential confounding effects of walking speed. Preoperatively, the THA vs. control group differences in the HROM and peak adduction moments were larger in women than they were in men (p=0.007). The THA group vs. control group difference in the peak external rotation moment was larger in men (p=0.004). After surgery, HROM increased more in women than in men (p=0.020). However, peak adduction moment decreased in men but increased in women (-0.11+/-0.93 vs. 0.28+/ 1.3%BWH, p=0.045). Accordingly, postoperatively the THA group vs. control group differences in the peak external rotation moment remained larger in men than in women (p=0.016). There were no other sex-specific differences (p=0.072-0.876). This study suggests that men and women have slightly different patterns of gait recovery after THA and may benefit from sex-specific rehabilitation strategies. These differences also underscore the importance of accounting for sex in biomechanical studies. PMID- 27663620 TI - Influence of intramuscular fiber orientation on the Achilles tendon curvature using three-dimensional finite element modeling of contracting skeletal muscle. AB - Tendon curvature plays a key role in mechanical gain (amplifying the joint excursion relative to fiber length change) during joint motion, but the mechanism remains unresolved. A three-dimensional finite element (FE) model was used to investigate the influence of intramuscular fiber orientation upon the curvature pattern of the Achilles tendon during active muscular contraction. Two simulation models, with fiber pennation angles of theta = 25 degrees and 47 degrees were tested for the gastrocnemius and soleus muscles. A smaller pennation angle (25 degrees ) of the soleus muscle fibers was accompanied by a large change in curvature whereas a larger pennation angle (47 degrees ) of the soleus muscle was accompanied by small effects. These results suggest that the fiber pennation angle determines the curvature of the tendon, and the magnitude of the curvature varies along the length of the aponeurosis. Such FE modeling has the potential of determining changes in force output consequent to changes in intramuscular fiber orientation arising from resistance training or unloading, and provides mechanism for predicting the risk of Achilles tendon ruptures. PMID- 27663622 TI - The effect of six degree of freedom loading sequence on the in-vitro compressive properties of human lumbar spine segments. AB - The complex, direction-dependent, poro-viscoelastic properties of the intervertebral disc (disc) suggest that investigations of the six degree of freedom (6DOF) behaviour may be susceptible to inter-test variation in mechanical response if the disc does not return to initial conditions between loading directions. No studies have quantified the effects of sequential multi directional loading on the consistency of the compressive response of the disc throughout a 6DOF testing protocol. Therefore, the objective of this study was to determine the effect of 6DOF loading on the compressive properties (stiffness and phase angle) of human discs, as evaluated by a reference compression test performed after each single DOF test. Fourteen intact human functional spinal units (FSU) were tested in each of +/-6DOFs (shear directions followed by bending and compression) across four orders of magnitude loading frequencies (0.001-1Hz), followed by reference compression tests while subjected to physiological preload, hydration, and body temperature conditions in a hexapod robot. Repeated measures ANOVA revealed significant within-subjects effects between the reference compression tests for modulus (p<0.001), stiffness (p<0.001), and phase angle (p=0.008). Significant post-hoc pairwise comparisons were initially seen between the control and other reference compression tests for stiffness and modulus after the shear DOFs, however, no significant differences were present after the final reference compression test compared to control. More pronounced effects were seen for stiffness in comparison to modulus and phase angle. These effects may be due to three potentials factors, which include the sequence of testing, the cohort of degenerative specimens, and/or cumulative creep due to the constant application of a follower load. While the sequence of test directions was chosen to minimise the biphasic effect, there may be other sequences, which could result in minimal changes in compressive properties. PMID- 27663621 TI - Impact of P2RX7 ablation on the morphological, mechanical and tissue properties of bones in a murine model of duchenne muscular dystrophy. AB - Duchenne muscular dystrophy (DMD) is an inherited, lethal disorder characterised by progressive muscle degeneration and associated bone abnormalities. We have previously demonstrated that P2RX7 purinergic receptors contribute to the pathogenesis of DMD, and found that P2RX7 ablation alleviated the severity of the disease. In this work we have used a dystrophic mdx mouse crossed with the global P2RX7 receptor to generate a knockout mouse (mdx/P2X7-/-), and compared its morphometric, mechanical and tissue properties against those of mdx, as well as the wild type (WT) and the P2RX7 knockout (P2X7-/-). Micro-computed tomography (uCT), three-point bending testing, scanning electron microscopy (SEM) and nano indentation were utilised in the study. The bones were analysed at approximately 4 weeks of age to examine the impact of P2RX7 ablation on the bone properties during the acute disease phase, before muscle wasting is fully developed. The results show that P2RX7 purinoceptor ablation has produced improvement or significant improvement in some of the morphological, the mechanical and the tissue properties of the dystrophic bones examined. Specifically, although the ablation produced smaller bones with significantly lower total cross-section area (Tt.Ar) and Second Moment of Area (SMA), significantly higher cortical bone area (Ct.Ar), cortical area fraction (Ct.Ar/Tt.Ar) and trabecular bone volume fraction (BV/TV) are found in the mdx/P2X7-/- mice than in any other types. Further, the mdx/P2X7-/- bones have relatively higher average flexural strength, work-to fracture and significantly higher strain to failure compared with those of mdx, suggesting greater resistance to fracture. Indentation modulus, elasticity and creep are also significantly improved in the knockout cortical bones over those of mdx. These findings seem to suggest that specific pharmacological blockade of P2RX7 may improve dystrophic bones, with a potential for therapeutic application in the treatment of the disease. PMID- 27663623 TI - Interleukin-12 modulates the immunomodulatory properties of human periodontal ligament cells. AB - BACKGROUND AND OBJECTIVE: The cytokine interleukin 12 (IL-12) has been implicated as a potent stimulator of tissue degradation in the pathogenesis of several inflammatory diseases, including periodontitis. In patients with periodontitis, an increased level of IL-12 is found in serum and gingival crevicular fluid. As inflammatory cytokines have been demonstrated to induce activation of the immunomodulatory properties of mesenchymal stem cells (MSCs), this study aimed to investigate the influence of IL-12 on these properties in human periodontal ligament (hPDL) cells. MATERIAL AND METHODS: Human PDL cells were isolated from periodontal tissue and incubated with 0-10 ng/mL of IL-12 for 24 h. The levels of expression of interferon gamma (IFN-gamma), indoleamine 2,3-dioxygenase (IDO) and human leukocyte antigen G (HLA-G), as well as of the stem cell markers, CD73, CD90 and CD105, were assessed by quantitative PCR. The level of IFN-gamma protein was measured by ELISA, and IDO activity was measured by activity assay. The participation of IFN-gamma in the expression of IDO and HLA-G was analyzed using neutralizing antibody against IFN-gamma. RESULTS: IL-12 upregulated the expression of IFN-gamma in a dose-dependent manner. Moreover, IL-12 induced the expression of the immunomodulatory proteins IDO and HLA-G via an IFN-gamma dependent pathway, as indicated by experiments using an IFN-gamma neutralizing antibody. Addition of exogenous IFN-gamma upregulated the expression of HLA-G and IDO. Expression of the stem cell markers CD73, CD90 and CD105, as well as the pluripotent markers Nanog homeobox, octamer-binding transcription factor 4 and SRY-box 2, were also upregulated in IL-12-treated hPDL cells. Finally, IL-12 inhibited osteogenic differentiation of the hPDL cells and preserved the self clonal expansion property of these cells, as assessed by Alizarin Red S staining and the colony-forming unit assay. CONCLUSION: Expression of IL-12 during periodontitis may play an important role in the control of the inflammatory response via the induction of immunosuppressive molecules by hPDL cells. We hypothesize that this immunomodulatory property of IL-12 will serve as a protective mechanism to preserve a population of stem cells under inflammatory conditions. PMID- 27663624 TI - Intentional gaze shift to neglected space: a compensatory strategy during recovery after unilateral spatial neglect. AB - Unilateral spatial neglect is a common neurological syndrome following predominantly right hemispheric stroke. While most patients lack insight into their neglect behaviour and do not initiate compensatory behaviours in the early recovery phase, some patients recognize it and start to pay attention towards the neglected space. We aimed to characterize visual attention capacity in patients with unilateral spatial neglect with specific focus on cortical processes underlying compensatory gaze shift towards the neglected space during the recovery process. Based on the Behavioural Inattention Test score and presence or absence of experience of neglect in their daily life from stroke onset to the enrolment date, participants were divided into USN+??+ (do not compensate, n = 15), USN+ (compensate, n = 10), and right hemisphere damage groups (no neglect, n = 24). The patients participated in eye pursuit-based choice reaction tasks and were asked to pursue one of five horizontally located circular objects flashed on a computer display. The task consisted of 25 trials with 4-s intervals, and the order of highlighted objects was randomly determined. From the recorded eye tracking data, eye movement onset and gaze shift were calculated. To elucidate the cortical mechanism underlying behavioural results, electroencephalagram activities were recorded in three USN+??+, 13 USN+ and eight patients with right hemisphere damage. We found that while lower Behavioural Inattention Test scoring patients (USN+??+) showed gaze shift to non-neglected space, some higher scoring patients (USN+) showed clear leftward gaze shift at visual stimuli onset. Moreover, we found a significant correlation between Behavioural Inattention Test score and gaze shift extent in the unilateral spatial neglect group (r = -0.62, P < 0.01). Electroencephalography data clearly demonstrated that the extent of increase in theta power in the frontal cortex strongly correlated with the leftward gaze shift extent in the USN+??+ and USN+ groups. Our results revealed a compensatory strategy (continuous attention to the neglected space) and its neural correlates in patients with unilateral spatial neglect. In conclusion, patients with unilateral spatial neglect who recognized their own neglect behaviour intentionally focused on the neglected space as a compensatory strategy to avoid careless oversight. PMID- 27663625 TI - Reply. PMID- 27663626 TI - Classifying medial rectus muscle attachment in consecutive exotropia. PMID- 27663627 TI - Clinical factors associated with moderate hyperopia in preschool children with normal stereopsis and visual acuity. AB - A total of 117 children 3-5 years of age with moderate hyperopia in at least one eye, age-normal unaided visual acuity, age-normal stereoacuity, no significant anisometropia or astigmatism, and no strabismus were enrolled in a 3-year randomized clinical trial to compare visual outcomes and ocular alignment in children assigned to immediate glasses or to observation and glasses if deterioration of visual acuity, stereoacuity, or alignment occurred. Pearson correlation coefficients were calculated to evaluate relationships among baseline characteristics. We found a moderate association between higher amounts of uncorrected hyperopia and greater accommodative lag (n = 57; R = 0.31; 95% CI, 0.05-0.53). Higher amounts of hyperopia were weakly associated with worse uncorrected distance visual acuity (n = 117; R = 0.24; 95% CI, 0.06-0.41), and better stereoacuity was weakly associated with better uncorrected near acuity (n = 99; R = 0.24; 95% CI, 0.04-0.42). PMID- 27663628 TI - Clinical significance of high levels of survivin and transforming growth factor beta-1 proteins in aqueous humor and serum of retinoblastoma patients. AB - PURPOSE: To evaluate the diagnostic and prognostic values of survivin and transforming growth factor beta-1 (TGF-B1) expression in aqueous humor and serum of retinoblastoma (RB) in comparison to the conventional RB marker lactate dehydrogenase (LDH) and to elucidate a possible correlation between them and the clinicopathological features of the disease. METHODS: This prospective, comparative study included 88 newly diagnosed children with RB and 80 age-matched controls with ophthalmic conditions other than tumors prepared for intraocular surgeries. Concentrations of survivin, TGF-B1, and LDH were measured in serum and aqueous humor before and 6 months after completion of therapy. RESULTS: High serum and aqueous humor concentrations of the three proteins were detected in RB patients before treatment compared to the control group (P < 0.01), with a significant reduction of serum concentrations after treatment (P < 0.01). For the highest sensitivity and specificity, the optimal cutoff values of serum and aqueous survivin were 12.9 pg/ml and 25.2 pg/mg, with a significant positive correlation between aqueous survivin and RB staging and presence of optic nerve infiltration (r = 0.43, P = 0.04); the best cutoff values of serum and aqueous TGF-B1, 370.7 pg/ml and 39.8 pg/mg, with a significant positive correlation between aqueous TGF-B1 and poor differentiation of the tumor (r = 0.69, P = 0.001). CONCLUSIONS: The high sensitivity, specificity, and accuracy of serum and aqueous humor survivin and TGF-B1 proteins make them promising markers for early detection and follow-up of RB patients. PMID- 27663629 TI - Comparison of augmented and nonaugmented modified Knapp procedure for the treatment of nonrestrictive double elevator palsies. AB - PURPOSE: To compare surgical results of augmented and nonaugmented modified Knapp procedure, for the treatment of nonrestrictive double elevator palsies (DEP). METHODS: The medical records of patients with congenital DEP were reviewed retrospectively. Patients were divided into three treatment groups: standard transposition (group A), Foster transposition (group B), and resection transposition (group C). Pre- and postoperative vertical deviation in primary position, ocular motility, and binocular vision were compared. RESULTS: Thirty patients were enrolled. The pre- and postoperative deviations in group A were 34.7Delta +/- 8.6Delta and 6.5Delta +/- 6.5Delta; in group B, 38.6Delta +/- 14.6Delta and 5.7Delta +/- 9.3Delta; and in group C, 43.1Delta +/- 10.3Delta and 8.5Delta +/- 6.1Delta. The corrected vertical deviation of group B (32.9Delta +/- 5.7Delta) and group C (34.6Delta +/- 5.0Delta) were greater than that of group A (28.1Delta +/- 3.6Delta; P = 0.03, 0.002). The pre- and postoperative measures of upgaze in group A were -3.7 and -1.8; in group B, -4.0 and -1.3; and in group C, 3.6 and -2.0. The average improved upgaze in group B (2.6 +/- 0.5) was statistically significantly better than that in group A (1.9 +/- 0.6) and group C (1.5 +/- 0.5; P = 0.03, 0.002). There was no significant difference in the surgical effect on downgaze in three groups (P > 0.05). The surgical outcome was satisfactory in 19 (63.3%) patients with preoperative vertical devation of <=40Delta. CONCLUSIONS: All transpositions are reasonably effective in treating vertical deviations of <35Delta without obviously limiting downgaze in DEP. Augmented procedures could correct greater vertical deviation of 30Delta-40Delta. The Foster transposition demonstrates the strongest effect in improving upgaze. PMID- 27663630 TI - Exotropic Duane syndrome with synergistic divergence and no mutations in COL25A1. AB - Typical Duane retraction syndrome, a common form of congenital cranial dysinnervation disorder (CCDD), is rarely due to a monogenic mutation. However, the unusual form of exotropic Duane syndrome with synergistic divergence was recently associated with bi-allelic mutations in the gene COL25A1, raising the possibility that this particular Duane syndrome phenotype could be a monogenic recessive CCDD. To explore this possibility, we tested 4 consecutive unrelated subjects with the diagnosis for COL25A1 mutations. None harbored pathogenic variants, evidence that exotropic Duane syndrome with synergistic divergence is notspecifically caused by mutations in the gene. PMID- 27663631 TI - Usefulness of the plasma glucose concentration-to-HbA1c ratio in predicting clinical outcomes during acute illness with extreme hyperglycaemia. AB - AIMS: To evaluate the correlation between the plasma glucose-to-glycated haemoglobin ratio (GAR) and clinical outcome during acute illness. METHODS: This retrospective observational cohort study enrolled 661 patients who visited the emergency department of our hospital between 1 July 2008 and 30 September 2010 with plasma glucose concentrations>500mg/dL. Systolic blood pressure, heart rate, white blood cells, neutrophils, haematocrit, blood urea nitrogen, serum creatinine, liver function and plasma glucose concentration were recorded at the initial presentation to the emergency department. Data on glycated haemoglobin over the preceding 6 months were reviewed from our hospital database. The glucose to-HbA1c ratio (GAR) was calculated as the plasma glucose concentration divided by glycated haemoglobin. RESULTS: The GAR of those who died was significantly higher than that of the survivors (81.0+/-25.9 vs 67.6+/-25.0; P<0.001). There was a trend towards a higher 90-day mortality rate in patients with higher GARs (log-rank test P<0.0001 for trend). On multivariate Cox regression analysis, the GAR was significantly related to 90-day mortality (hazard ratio [HR] for 1 standard deviation [SD] change: 1.41, 95% confidence interval [CI]: 1.22-1.63; P<0.001), but not to plasma glucose (HR: 0.89, 95% CI: 0.70-1.13; P=0.328). Rates of intensive care unit (ICU) admission and mechanical ventilator use were also higher in those with higher GARs. CONCLUSION: GAR independently predicted 90-day mortality, ICU admission and use of mechanical ventilation. It was also a better predictor of patient outcomes than plasma glucose alone in patients with extremely high glucose levels. PMID- 27663632 TI - The effects of stress on the dorsal raphe nucleus of the reticular formation and its role in the aetiology of disparate medical and neuropsychiatric disorders. PMID- 27663633 TI - Response to "Data Interpretation on the Use of Double-Lumen Tube Versus Bronchial Blocker for One-Lung Ventilation". PMID- 27663634 TI - Recurrent Asystole After Neostigmine in a Heart Transplant Recipient With End Stage Renal Disease. PMID- 27663635 TI - Quantification of all 209 PCB congeners in blood-Can indicators be used to calculate the total PCB blood load? AB - Polychlorinated biphenyls (PCBs) are a substance group of 209 theoretically possible compounds. The human body burden of PCBs is commonly calculated based on so-called indicator congeners such as PCB 138, PCB 153 and PCB 180, which are analyzed in human blood. The German "Human Biomonitoring (HBM) Commission" assumes that the sum of these indicator congeners multiplied by a factor of 2 represents the total PCB burden. This norm is based on data obtained from exposure studies after dietary intake. Data from indoor air shows a different congener pattern, which might lead to a relatively higher intake of lower chlorinated PCBs by inhalation. In two independent studies with adult participants from two regions in Germany, we measured all 209 PCB congeners in 44 whole blood and 42 plasma samples. Participants from the whole blood study group had additional exposure to PCBs via indoor air. With our analytical method, 141 individual PCB congeners, 27 coeluted pairs of PCB congeners and 2 records of 3 and 4 coeluted PCBs could be determined. Thus, 172 analysis results were reported per sample. In the whole blood samples, 50 congeners showed values below the limit of quantification (LOQ), whereas 94 congeners could not be detected in any of plasma samples. Total PCB concentrations (Sigma 209 PCB congeners, incl. 1/2 LOQ) in the whole blood samples ranged from 99 to 2152ng PCB/g lipid (Median: 454ng/g lipid; 95th Percentile: 1404ng/g lipid). The sum of all 209 measured PCB (incl. 1/2 LOQ) in plasma samples showed levels between 52 and 933ng PCB/g lipid (Median: 226ng/g lipid; 95th Percentile: 642ng/g lipid). Our results show that the burden of PCBs on the human body is caused mainly by the three highly chlorinated indicator congeners PCB 138, PCB 153 and PCB 180. In median approximately 50% of the total PCB content in human whole blood or plasma samples can be attributed to these congeners. Total PCB, calculated by multiplying the sum of the three indicator congeners by 2, showed a strong and highly significant correlation to the sum of all 209 measured congeners for each sample. A slightly stronger correlation in the whole blood samples could be achieved by choosing six indicator congeners, including the lower chlorinated congeners (PCB 28, 52 and 101) into the calculation. Although this difference is very small, it must be considered that higher PCB levels in indoor air than those measured in the present study might be associated with a higher burden of indoor-air-related congeners in exposed individuals. For precautionary reasons, it could therefore be recommended that the assessment of individuals exposed to PCB via indoor air should be carried out based on the sum of the 6 indicator congeners PCB 28, PCB 52, PCB 101, PCB 138, PCB 153 and PCB 180 multiplied by a factor of 2. PMID- 27663636 TI - Human biomonitoring in Israel: Recent results and lessons learned. AB - The use of human biomonitoring (HBM) as a tool for environmental health policy and research is developing rapidly in Israel. Despite challenges in securing political and financial support for HBM, the Ministry of Health has initiated national HBM studies and has utilized HBM data in environmental health policy decision making. Currently, the Ministry of Health is collecting urine samples from children and adults in the framework of the National Health and Nutrition Study (MABAT), with the goal of ongoing surveillance of population exposure to pesticides and environmental tobacco smoke, and of combining HBM data with data on diet and health behavior. In academic research studies in Israel, biomarkers are used increasingly in environmental epidemiology, including in three active birth cohort studies on adverse health effects of phthalates, brominated flame retardants, and organophosphate pesticides. Future Ministry of Health goals include establishing HBM analytical capabilities, developing a long term national HBM plan for Israel and participating in the proposed HBM4EU project in order to improve data harmonization. One of the lessons learned in Israel is that even in the absence of a formal HBM program, it is possible to collect meaningful HBM data and use it in an ad hoc fashion to support environmental health policy. PMID- 27663638 TI - PET imaging approaches for inflammatory lung diseases: Current concepts and future directions. AB - Inflammatory lung disease is one of the most common clinical scenarios, and yet, it is often poorly understood. Inflammatory lung disorders, such as chronic obstructive pulmonary diseases, which are causing significant mortality and morbidity, have limited therapeutic options. Recently, new treatments have become available for pulmonary fibrosis. This review article will describe the new insights that are starting to be gained from positron emission tomography (PET) methods, by targeting molecular processes using dedicated radiotracers. Ultimately, this should aid in deriving better pathophysiological classification of these disorders, which will ultimately result in better evaluation of novel therapies. PMID- 27663639 TI - Editorial Comment. PMID- 27663637 TI - Germline variants in ETV6 underlie reduced platelet formation, platelet dysfunction and increased levels of circulating CD34+ progenitors. AB - Variants in ETV6, which encodes a transcription repressor of the E26 transformation-specific family, have recently been reported to be responsible for inherited thrombocytopenia and hematologic malignancy. We sequenced the DNA from cases with unexplained dominant thrombocytopenia and identified six likely pathogenic variants in ETV6, of which five are novel. We observed low repressive activity of all tested ETV6 variants, and variants located in the E26 transformation-specific binding domain (encoding p.A377T, p.Y401N) led to reduced binding to corepressors. We also observed a large expansion of megakaryocyte colony-forming units derived from variant carriers and reduced proplatelet formation with abnormal cytoskeletal organization. The defect in proplatelet formation was also observed in control CD34+ cell-derived megakaryocytes transduced with lentiviral particles encoding mutant ETV6. Reduced expression levels of key regulators of the actin cytoskeleton CDC42 and RHOA were measured. Moreover, changes in the actin structures are typically accompanied by a rounder platelet shape with a highly heterogeneous size, decreased platelet arachidonic response, and spreading and retarded clot retraction in ETV6 deficient platelets. Elevated numbers of circulating CD34+ cells were found in p.P214L and p.Y401N carriers, and two patients from different families suffered from refractory anemia with excess blasts, while one patient from a third family was successfully treated for acute myeloid leukemia. Overall, our study provides novel insights into the role of ETV6 as a driver of cytoskeletal regulatory gene expression during platelet production, and the impact of variants resulting in platelets with altered size, shape and function and potentially also in changes in circulating progenitor levels. PMID- 27663640 TI - Author Reply. PMID- 27663641 TI - Editorial Comment. PMID- 27663643 TI - Practice patterns for complex situations in the management of rectal cancer: A multidisciplinary inter-group national survey. AB - GOAL: To report the current clinical practice of French physicians for rectal cancer in various complex settings. METHODS: Nineteen clinical situations and four surveillance modalities were proposed to a panel of experts via 11 learned societies. The answers of 48 experts and the impact of colorectal specialists on therapeutic options were compared to those of other participants. RESULTS: A total of 722 physicians [surgeons=319 (44%), gastro-intestinal oncologists=305 (42%), radiotherapists=98 (14%)] participated in this study. The mean number of answers per question was 500. A consensus was reached in 19 clinical situations. Approaches according to specialty were similar in most situations. In seven settings, the therapeutic strategy differed significantly (interval between the end of chemo-radiation and surgery, attitude based on response of neo-adjuvant therapy, treatment of usT1N0 or pT1sm2 tumors after endoscopic resection, adjuvant therapy for pT3N1 tumors, interval to protective stoma closure, and schedule of follow-up surveillance). There was disagreement between experts and non-experts with regard to three management plans (contra-indications for neo adjuvant chemo-radiation therapy, strategy according to response to neo-adjuvant therapy, and date of protective stoma closure). CONCLUSION: This survey provides an overview of current practice of a selected group of French physicians. Sound knowledge of the current literature and case-by-case discussion with a group of experts from each involved specialty during a multidisciplinary conference are essential. Certain complex cases should be presented to expert centers to validate the therapeutic approach. PMID- 27663644 TI - Distribution, sources, and ecological risk assessment of polycyclic aromatic hydrocarbons in surface sediments from the Nantong Coast, China. AB - The distribution, sources, and ecological risk assessment of 16 polycyclic aromatic hydrocarbons (PAHs) in surface sediments from the Nantong coast in China were investigated. The results indicated that the total concentrations of the 16 PAHs in the surface sediments from the study area ranged from 1.4 to 87.1ngg-1 dw (mean value 19.9ngg-1 dw), which were generally low compared to the adjacent offshore area and other coastal zones around the world. The selected PAH ratios and the principal components analysis for each site showed that petroleum combustion and petrogenic pollution (mainly caused by petroleum spills) were the dominant PAHs sources in the surface sediments of the coast. The ecological risk assessment indicated that most of the individual PAHs had few negative effects in this area. PMID- 27663642 TI - Breast cancer screening attendance in two Swiss regions dominated by opportunistic or organized screening. AB - BACKGROUND: In Switzerland, the French-speaking region has an organized breast cancer (BC) screening program; in the German-speaking region, only opportunistic screening until recently had been offered. We evaluated factors associated with attendance to breast cancer screening in these two regions. METHODS: We analyzed the data of 50-69 year-old women (n = 2769) from the Swiss Health Survey 2012. Factors of interest included education level, place of residence, nationality, marital status, smoking history, alcohol consumption, physical activity, diet, self-perceived health, history of chronic diseases and mental distress, visits to medical doctors and cervical and colorectal cancer screening. Outcome measures were dichotomized into <=2 years since most recent mammography versus >2 years or never. RESULTS: In the German- and French-speaking regions, mammography attendance within the last two years was 34.9 % and 77.8 %, respectively. In the French region, moderate alcohol consumption (adjusted OR 2.01, 95 % CI 1.28-3.15) increased screening attendance. Compared to those with no visit to a physician during the recent year, women in both regions with such visits attended statistically significantly more often BC screening (1-5 times vs. no visit: German (adjusted OR 3.96, 95 % CI 2.58-6.09); French: OR 7.25, 95 % CI 4.04 13.01). Non-attendance to cervical screening had a negative effect in both the German (adjusted OR 0.44, 95 % CI 0.25-0.79) and the French region (adjusted OR 0.57, 95 % CI 0.35-0.91). The same was true for colorectal cancer screening (German (adjusted OR 0.66, 95 % CI 0.52-0.84); French: OR 0.52, 95 % CI 0.33 0.83). No other factor was associated with BC screening and none of the tests of interaction comparing the two regions revealed statistically significant results. CONCLUSION: The effect of socio-demographic characteristics, lifestyle, health factors and screening behavior other than mammography on non-attendance to BC screening did not differ between the two regions with mainly opportunistic and organized screening, respectively, and did not explain the large differences in attendance between regions. Other potential explanations such as public promotion of attendance for BC screening, physicians' recommendations regarding mammography participation or women's beliefs should be further investigated. PMID- 27663645 TI - Distribution variation of heavy metals in maricultural sediments and their enrichment, ecological risk and possible source-A case study from Zhelin bay in Southern China. AB - The study characterized the enrichment, ecological risk and possible source of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) in sediments from a typical mariculture bay. The concentrations of the metals were analyzed in sediments collected from Zhelin bay. The distribution variation was examined during the past decade, which had an increase tendency till 2011. The enrichment factor and geoaccumulation indices suggested Pb, As, Cu and Zn were minor enrichment and unpolluted to moderately polluted, and Ni at cage mariculture area was moderately severe enrichment and strongly polluted. This area had medium to high ecological risk, especially at the northwest coastal area of semi-closed bay, with high medium to high ecological risk. Correlation and principal component analyses indicated that most of heavy metals, especially for As, Pb and Ni, primarily resulted from the combustion of gasoline and diesel fuel and the ship protective layer. PMID- 27663647 TI - A case of low success of blind vaccination campaigns against myxomatosis and rabbit haemorrhagic disease on survival of adult European wild rabbits. AB - Vaccination campaigns against myxomatosis and rabbit haemorrhagic disease (RHD) are commonly used in translocation programs conducted for the purpose of recovering wild European rabbit populations in Iberian Mediterranean ecosystems. In most cases rabbits are vaccinated 'blind' (i.e. without assessing their prior immunological status) for economic and logistic reasons. However, there is conflicting evidence on the effectiveness of such an approach. We tested whether blind vaccination against myxomatosis and rabbit haemorrhagic disease improved rabbit survival in a rabbit translocation program where wild rabbits were kept in semi-natural conditions in three enclosures. We conducted nine capture sessions over two years (2008-2010) and used the information collected to compare the survival of vaccinated (n=511) versus unvaccinated (n=161) adult wild rabbits using capture-mark-recapture analysis. Average monthly survival was no different for vaccinated versus unvaccinated individuals, both in the period between release and first capture (short-term) and after the first capture onward (long term). Rabbit survival was lower in the short term than in the long term regardless of whether rabbits were vaccinated or not. Lower survival in the short term could be due to the stress induced by the translocation process itself (e.g. handling stress). However, we did not find any overall effect of vaccination on survival which could be explained by two non-exclusive reasons. First, interference of the vaccine with the natural antibodies in the donor population. Due to donor populations have high density of rabbits with, likely, high prevalence of antibodies as a result of previous natural exposure to these diseases. Second, the lack of severe outbreaks during the study period. Based on our findings we argue that blind vaccination of adult rabbits in translocation programs may be often mostly ineffective and unnecessarily costly. In particular, since outbreaks are hard to predict and vaccination of rabbits with natural antibodies is ineffective, it is crucial to assess the immunological status of the donor population before translocating adult rabbits. PMID- 27663646 TI - Leptin decreases the expression of low-density lipoprotein receptor via PCSK9 pathway: linking dyslipidemia with obesity. AB - BACKGROUND: Previous studies have suggested that people with obesity showed elevated serum levels of leptin as well as lipid dysfunction and proprotein convertase subtilisin/kexin type 9 (PCSK9) played an important role in the regulation of lipid metabolism recently. The aim of this study was to determine if leptin participated in regulating the uptake of low-density lipoproteins (LDL) in hepatocytes via PCSK9. METHODS: HepG2 cells were treated with human recombinant leptin. The impact of leptin on cellular low density lipoprotein receptor (LDLR) and PCSK9 protein levels was determined by Western blot. Dil-LDL uptake assay was performed to examine the LDLR function. Specific small interfering RNAs (siRNAs) were used to interfere the expressions of target proteins. RESULTS: The expression of LDLR and LDL uptake could be significantly down-regulated by leptin treatment while the expressions of PCSK9 and hepatocyte nuclear factor 1alpha (HNF1alpha) were enhanced in HepG2 cells. Furthermore, inhibition of PCSK9 or HNF1alpha expression by siRNAs rescued the reduction of LDLR expression and LDL uptake by leptin. We found that leptin activated the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. Moreover, the changes of the expressions of HNF1alpha, PCSK9, LDLR, and LDL uptake induced by leptin could be blocked by p38MAPK inhibitor (SB203580). Additionally, leptin attenuated the up-regulation of LDLR caused by atorvastatin in HepG2 cells. CONCLUSIONS: These findings indicated firstly that leptin reduced LDLR levels in hepatocyte via PCSK9 pathway, suggesting that PCSK9 might be a alternative target for dyslipidemia in the obesity. PMID- 27663648 TI - Do we need new prokinetics to reduce enteral feeding intolerance during critical illness? AB - Gastrointestinal feeding intolerance and critical illness-associated gastric motility dysfunction are common. Although recent guidelines recommend not interrupting gastric feeding when gastric residual volume (GRV) is lower than 500 mL or to completely abandon measurement of GRV, it may seem that the relevance of prokinetics is reduced.In patients at risk for aspiration and in multimodal strategies to enhance feeding performance, however, use of prokinetics is still advocated. Metoclopramide and erythromycin are commonly used promotility agents, although with relevant side effects.Potential targets for new agents and early study results are addressed. PMID- 27663649 TI - Throat culture positivity rate and antibiotic susceptibility pattern of beta hemolytic streptococci in children on secondary prophylaxis for rheumatic heart disease. AB - BACKGROUND: Among children diagnosed to have chronic rheumatic valvular heart disease (RHD) in Ethiopia, many have been observed to develop recurrence of rheumatic fever (RF) despite secondary prophylaxis. This study determined the throat culture positivity rate and drug susceptibility pattern of beta hemolytic streptococci (BHS) isolated from children attending a specialized cardiac clinic in Ethiopia. METHODS: Throat swabs were collected from 233 children receiving benzathine penicillin injection as secondary prophylaxis for RHD and cultured. The bacterial isolates were characterized using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry. Drug susceptibility was tested with the Kirby Bauer disc diffusion method. Anti streptolysin O (ASO) titers were determined using ASO latex reagents. RESULTS: The throat culture positivity rate for BHS was 24 % (56/233). Among the BHS bacterial strains isolated, four were characterized as S. pyogenes and another four as S. dysgalactiae subsp. equisimilis (Lancefield group A, C and G). All BHS were susceptible to penicillin except one isolate of S. agalactiae. Among 233 children enrolled, 46(19.7 %) showed increased ASO titer. Children who received antibiotic prophylaxis within 2-weeks of last injection had significantly lower BHS throat culture positivity rate than those injected every 4-weeks (p = 0.02). Children who missed at least one prophylaxis within the last 6 months had a higher BHS culture positivity rate than those who did not miss any (p = 0.0003). CONCLUSIONS: The presence of groups A, C and G streptococci in the throat of children under secondary prophylaxis for RHD and increased ASO titer suggests failure of the regimen. This calls for further investigation into the causes of inadequate prophylaxis (including bioavailability of drugs used, optimal duration and patient compliance) and intervention. PMID- 27663650 TI - Rib fractures and their association With solid organ injury: higher rib fractures have greater significance for solid organ injury screening. AB - BACKGROUND: The purpose of this study was to identify patients with rib injuries who were at risk for solid organ injury. METHODS: A retrospective chart review was performed of all blunt trauma patients with rib fractures during the period from July 2007 to July 2012. Data were analyzed for association of rib fractures and solid organ injury. RESULTS: In all, 1,103 rib fracture patients were identified; 142 patients had liver injuries with 109 (77%) associated right rib fractures. Right-sided rib fractures with highest sensitivity for liver injury were middle rib segment (5 to 8) and lower segment (9 to 12) with liver injury sensitivities of 68% and 43%, respectively (P < .001); 151 patients had spleen injuries with 119 (79%) associated left rib fractures. Left middle segment rib fractures and lower segment rib fractures had sensitivities of 80% and 63% for splenic injury, respectively (P < .003). CONCLUSIONS: Rib fractures higher in the thoracic cage have significant association with solid organ injury. Using rib fractures from middle plus lower segments as indication for abdominal screening will significantly improve rib fracture sensitivity for identification of solid organ injury. PMID- 27663651 TI - Conscious status predicts mortality among patients with isolated traumatic brain injury in administrative data. AB - BACKGROUND: Outcome studies in trauma using administrative data traditionally employ anatomy-based definitions of injury severity; however, physiologic factors, including consciousness, may correlate with outcomes. We examined whether accounting for conscious status in administrative data improved mortality prediction among patients with moderate to severe TBI. METHODS: Patients meeting Centers for Disease Control and Prevention (CDC) guidelines for TBI in the 2006 to 2011 Nationwide Emergency Department Sample were identified. Patients were dichotomized as having no/brief loss of consciousness (LOC) vs extended LOC greater than 1 hour using International Classification of Diseases, Ninth Revision (ICD-9) fifth digit modifiers. Receiver operating curves compared the ability of logistic regression to predict mortality in models that included LOC vs models that did not. RESULTS: Overall, 98,397 individuals met criteria, of whom 25.8% had extended LOC. In univariate analysis, AIS alone predicted mortality in 69.6% of patients (area under receiver operating characteristic curve .696, 95% CI .689 to .702), extended LOC alone predicted mortality in 76.8% (AUROC .768, 95% CI .764 to .773), and a combination of AIS and extended LOC predicted mortality in 82.6% of cases (AUROC .826, 95% CI .821 to .830). Similar differences were observed in best-fit models. CONCLUSIONS: Accounting for LOC along with anatomical measures of injury severity improves mortality prediction among patients with moderate/severe TBI in administrative datasets. Further work is warranted to determine whether other physiological measures may also improve prediction across a variety of injury types. PMID- 27663652 TI - Amino acid substitutions involved in the adaptation of a novel highly pathogenic H5N2 avian influenza virus in mice. AB - BACKGROUND: H5N2 avian influenza viruses (AIVs) can infect individuals that are in frequent contact with infected birds. In 2013, we isolated a novel reassortant highly pathogenic H5N2 AIV strain [A/duck/Zhejiang/6DK19/2013(H5N2) (6DK19)] from a duck in Eastern China. This study was undertaken to understand the adaptive processes that led enhanced replication and increased virulence of 6DK19 in mammals. 6DK19 was adapted to mice using serial lung-to-lung passages (10 passages total). The virulence of the wild-type virus (WT-6DK19) and mouse adapted virus (MA-6DK19) was determined in mice. The whole-genome sequences of MA 6DK19 and WT-6DK19 were compared to determine amino acid differences. FINDINGS: Amino acid changes were identified in the MA-DK19 PB2 (E627K), PB1 (I181T), HA (A150S), NS1 (seven amino acid extension "WRNKVAD" at the C-terminal), and NS2 (E69G) proteins. Survival and histology analyses demonstrated that MA-6DK19 was more virulent in mice than WT-6DK19. CONCLUSION: Our results suggest that these substitutions are involved in the enhanced replication efficiency and virulence of H5N2 AIVs in mammals. Continuing surveillance for H5N2 viruses in poultry that are carrying these mutations is required. PMID- 27663653 TI - Completed Sonographic Anatomic Surveys: The Exception Rather Than the Rule. AB - OBJECTIVES: To determine how often fetal organ systems are imaged completely and whether this rate varies by hospital. METHODS: All initial sonographic anatomic examinations between 16 and 24 weeks from 3 hospitals (perinatal designation levels I-III) from January 2012 through December 2013 were identified in their obstetric and gynecologic anatomic survey report databases, focusing on 36 anatomic fields. Structures were grouped into regions: brain, face, spine, heart, abdomen, and extremities. Rates of complete visualization of each structure, structure grouping, and the total were calculated and compared by chi2 testing. RESULTS: From 7211 examinations (2578 from level I, 986 from level II, and 3647 from level III), the completion rate was 16.8% (I, 20.6%; II, 20.0%; and III, 13.2%; P < .00001). Brain and extremity imaging was complete 85% of the time or more but spine only 62.4% (sacrum consistently lowest). Completeness rates varied significantly (P< .00001) for the face (28.1%-64.4%, due to low rates of clearing lips at level III, and level I not clearing profiles), heart (37.3%-56.1%, level I < II < III), and abdomen (65.2%-85.7%, due to lower rates of clearing kidneys at level I). Completion of both the heart and spine was 32.0% (I, 23.0%; II, 25.4%; and III, 40.2%; P < .00001). CONCLUSIONS: With a comprehensive reporting system, completion rates for full anatomic sonograms are low. Facial, cardiac, and spinal structures are least complete, and follow-up examinations often remain incomplete. Completion benchmarks would be helpful because "incomplete" studies lead to repeated examinations that increase health care costs. PMID- 27663654 TI - Greater Trochanteric Pain Syndrome: Percutaneous Tendon Fenestration Versus Platelet-Rich Plasma Injection for Treatment of Gluteal Tendinosis. AB - OBJECTIVES: The purpose of this study was to compare ultrasound-guided percutaneous tendon fenestration to platelet-rich plasma (PRP) injection for treatment of greater trochanteric pain syndrome. METHODS: After Institutional Review Board approval was obtained, patients with symptoms of greater trochanteric pain syndrome and ultrasound findings of gluteal tendinosis or a partial tear (<50% depth) were blinded and treated with ultrasound-guided fenestration or autologous PRP injection of the abnormal tendon. Pain scores were recorded at baseline, week 1, and week 2 after treatment. Retrospective clinic record review assessed patient symptoms. RESULTS: The study group consisted of 30 patients (24 female), of whom 50% were treated with fenestration and 50% were treated with PRP. The gluteus medius was treated in 73% and 67% in the fenestration and PRP groups, respectively. Tendinosis was present in all patients. In the fenestration group, mean pain scores were 32.4 at baseline, 16.8 at time point 1, and 15.2 at time point 2. In the PRP group, mean pain scores were 31.4 at baseline, 25.5 at time point 1, and 19.4 at time point 2. Retrospective follow-up showed significant pain score improvement from baseline to time points 1 and 2 (P< .0001) but no difference between treatment groups (P= .1623). There was 71% and 79% improvement at 92 days (mean) in the fenestration and PRP groups, respectively, with no significant difference between the treatments (P >.99). CONCLUSIONS: Our study shows that both ultrasound-guided tendon fenestration and PRP injection are effective for treatment of gluteal tendinosis, showing symptom improvement in both treatment groups. PMID- 27663655 TI - Sonoelastography of Musculoskeletal Soft Tissue Masses: A Pilot Study of Quantitative Evaluation. AB - OBJECTIVES: To evaluate quantitative sonoelastography of benign and malignant musculoskeletal soft tissue masses. METHODS: We conducted a prospective study of 50 patients from a specialist sarcoma center who had extremity soft tissue masses referred for biopsy. After consent, the quantitative shear wave velocity (meters per second) was measured in longitudinal and transverse planes (3 readings in each plane and mean calculated). All masses subsequently underwent biopsy, excision, or both, with the histologic diagnosis taken as the reference standard. At a subsequent sitting, all anonymized B-mode sonograms were scored independently by 2 radiologists as benign or malignant with agreement by consensus if necessary. RESULTS: Of the 50 masses, 15 were malignant and 35 benign. Nine masses had incomplete velocity readings. Intraclass correlation coefficients for intra-reader reliability of velocity measurements were highly repeatable. There was preliminary evidence that the longitudinal shear wave velocity of malignant masses was on average 30% slower than that of benign masses (P< .10). Longitudinal and transverse shear wave measurements were moderately associated with each other (P = .003). There was no evidence that shear wave velocity varied with patient age, sex, or mass volume. For B-mode assessment of malignancy, sensitivity (Wilson 90% confidence interval) was 73.3% (52.1%, 87.4%), and specificity was 77.1% (63.8%, 86.6%). Interobserver agreement was substantial (kappa= 0.86). Four of 15 malignant masses (26.6%) were incorrectly classified as benign on B-mode assessment (all grade 1 liposarcomas). CONCLUSIONS: These data suggest that shear wave velocity measurement is reproducible and that malignant masses may have slower longitudinal shear wave velocities than benign masses. The sample size of this pilot study precludes adjusted analysis but should form the basis for larger study designs. PMID- 27663656 TI - Liver and Spleen Stiffness Measurements by Point Shear Wave Elastography via Acoustic Radiation Force Impulse: Intraobserver and Interobserver Variability and Predictors of Variability in a US Population. AB - OBJECTIVES: Measurements of liver stiffness and spleen stiffness are useful noninvasive ways to assess fibrosis and portal hypertension in patients with chronic liver disease. One method for assessing stiffness is by point shear wave elastography via acoustic radiation force impulse imaging (ARFI). Its advantage is that sites where stiffness is measured are visualized sonographically. However, its reliability has not been well established, and all studies done to date evaluating the use of ARFI in chronic liver disease have been performed outside the United States. We aimed to characterize the intraobserver and interobserver variability of ARFI-measured liver and spleen stiffness. METHODS: Two hepatologists evaluated unselected hepatology outpatients with ARFI. Exclusions were hepatocellular carcinoma, ascites, a surgical shunt or transjugular intrahepatic portosystemic shunt, portal thrombosis, and cholestatic disease. Each operator obtained 20 measurements from the right liver lobe and spleen. Intraclass correlation coefficients (ICC) were calculated. RESULTS: A total of 177 patients were included: median age, 61 years; 85% male; and 43% obese. Intraobserver ICCs were the same for both observers for liver stiffness (0.89; 95% confidence interval [CI], 0.85-0.92) and spleen stiffness (0.72; 95% CI, 0.61-0.80). Interobserver agreement was excellent for liver stiffness (ICC, 0.85; 95% CI, 0.76-0.90) but not as good for spleen stiffness (ICC, 0.73; 95% CI, 0.60-0.83). A body mass index of 30 kg/m2 or greater, waist circumference of greater than 105 cm, and skin-to-capsule distance of 2 cm or greater negatively affected the ICC for liver stiffness; small spleen size negatively affected the ICC for spleen stiffness. CONCLUSIONS: To our knowledge, this article is the first report of ARFI findings in a US population with chronic liver disease. Liver stiffness reproducibility was excellent, particularly in nonobese patients. Spleen stiffness reproducibility was excellent in those with larger spleens and therefore may be most useful in patients with cirrhosis and portal hypertension. PMID- 27663657 TI - Effects of Cigarette Smoking on Elastographic Strain Ratio Measurements of Patellar and Achilles Tendons. AB - OBJECTIVES: The aim of this study was to explore the sonographic and elastographic properties of patellar and Achilles tendons in smoking and nonsmoking otherwise healthy adults. METHODS: We conducted a level 3 case-control analytical study. Smoking and nonsmoking volunteers (>18 years) without musculoskeletal system disorders were included in the study. Demographic characteristics and smoking habits (pack-years) were recorded. Proximal, middle, and distal third thicknesses of the patellar and Achilles tendons were measured by B-mode sonography. Strain ratio measurements of the same regions were measured by real-time ultrasound elastography. RESULTS: A total of 69 participants (57 male and 12 female; mean age +/- SD, 35.5 +/- 7.8 years) were evaluated in the study. Smoking (n = 35) and nonsmoking (n = 34) groups had no significant differences in terms of age, body mass index, sex, and activity level (all P > .05). Proximal, middle, and distal thirds of the patellar and Achilles tendons were significantly thinner in the smoking group (all P < .05). Furthermore, strain ratio measurements in the same regions were significantly lower in the smoking group (all P< .05). Patellar tendon thicknesses and strain ratios had negative correlations with the smoking amount (all P < .05). CONCLUSIONS: Thickness and strain ratio measurements of patellar and Achilles tendons were reduced (thinner and harder tendons) in smokers. Clinical implications of these morphologic and elastographic changes should be investigated in future studies. PMID- 27663659 TI - Effects of an integrated neighborhood approach on older people's (health-related) quality of life and well-being. AB - BACKGROUND: Integrated neighborhood approaches (INAs) are increasingly advocated to reinforce formal and informal community networks and support community dwelling older people. They aim to augment older people's self-management abilities and engage informal networks before seeking professional support. INAs' effectiveness however remains unknown. We evaluated an INA's effects on older people's (health-related) quality of life (HRQoL) and well-being in Rotterdam. METHODS: We used a matched quasi-experimental design comparing INA with "usual" care and support. Community-dwelling frail older (70+ years) people and frailty- and gender-matched control subjects (n = 186 each) were followed over a 1-year period (measurements at baseline and 6 and 12 months). Primary outcomes were HRQoL (EQ-5D-3L, SF-20) and well-being [social production function instrument for the level of well-being (SPF-IL)]. The effect of INA was analysed using an "intention to treat" and an "as treated" approach. RESULTS: The results indicated that pre-intervention participants had lower incomes and were significantly older, more often single, less educated and more likely to have >=1 disease than control subjects; they had lower well-being, physical functioning, role functioning, and mental health. Generalized linear mixed modelling of repeated measurements revealed no substantial difference in well-being or HRQoL between the intervention and control group after 1 year. The small differences we did find in the intention to treat group though were in favour of the control subjects (SF-20 = 6.98, 95 % confidence interval [CI] = 2.45-11.52; SPF-IL = .09, 95 % CI = .01-.17). However, the difference in well-being (SPF-IL) disappeared in the as treated analysis. CONCLUSIONS: The lack of effects of INA highlights the complexity of integrated care and support initiatives. Barriers associated with meeting the complex, varied needs of frail older people, and those related to dynamic political and social climates challenge initiative effectiveness. Trial registration The research was supported with a grant provided by the Netherlands Organisation for Health Research and Development (ZonMw, project number 314030201) as part of the National Care for the Elderly Programme. PMID- 27663658 TI - Development of an efficient strategy to improve HPV immunization coverage in Japan. AB - BACKGROUND: In Japan, new HPV immunizations have dropped dramatically after repeated adverse media reports and a June 2013 temporary suspension of the government's recommendation for the vaccine. The aim of the present study was to develop an efficient strategy to improve HPV immunization coverage across Japan. METHODS: We conducted an internet survey in Japan of mothers of 12-16 year-old girls who were unvaccinated as of May, 2015. The goal was to gather behavioral information from the mothers to develop a strategy for improving Japanese HPV immunization coverage. RESULTS: Valid survey answers were obtained from 2060 mothers. The survey found that a hypothetical restart of a governmental recommendation for the vaccine would induce 4.1 % of all the mothers surveyed to be more likely to encourage vaccination of their daughters, without any other preconditions. This initial result would be followed by a moderate spread of vaccinations to these daughters' close friends and acquaintances, hypothetically resulting in a total vaccination rate of 21.0 % of the targeted age-eligible girls. As a second critical step for improving vaccinations, an educational information sheet integrating the concepts of behavioral economics for changing behaviors was found to be significantly effective for persuading mothers with poorer decision-making facilities, who would otherwise prefer to wait to first see the vaccination of other girls of the same age as their daughter. CONCLUSIONS: Following what we foresee as the inevitable restart of the Japanese government's recommendation for receiving the HPV vaccine, we expect to first see vaccinations occurring in a very small group of girls, the daughters of the most willing mothers, which will be roughly 4 % of those eligible for government paid vaccinations. This will be followed by the spread of vaccinations outward through these girls' circle of friends and acquaintances, and, finally, to the daughters of the most skeptical mothers, those who would await the return of new vaccine safety results from a large group of similarly-aged girls. As a critical step in improving HPV vaccine coverage in Japan, an educational information sheet that integrates the concepts of behavioral economics for changing behaviors can be employed to persuade mothers with poor decision-making facilities. PMID- 27663660 TI - MicroRNA-215 suppresses cell proliferation, migration and invasion of colon cancer by repressing Yin-Yang 1. AB - Colorectal cancer is one of the most common malignant tumors worldwide with rising incidence. MicroRNAs are small non-coding RNAs that implicate in multiple physiological or pathological processes. The aberrant expression of miRNA-215 (miR-215) has been illustrated in various types of cancers. However, the expression of miR-215 in human colon cancer and the biological roles of it remain largely unknown. We conducted this study to explore the expression and the function of miR-215 in human colon cancer. The results showed that miR-215 was remarkably downregulated in colon cancer tissues and cell lines. Overexpression of miR-215 by miR-215 mimic significantly inhibited colon cancer cell proliferation, migration and invasion while knockdown of miR-215 by miR-215 inhibitor exerted reverse effects. Furthermore, we newly identified Yin-Yang 1(YY1) as a direct target of miR-215 which could rescue the effects of miR-215 on colon cancer cells. In summary, our investigation revealed that miR-215 was downregulated in colon cancer and it suppressed colon cancer cell proliferation, migration and invasion by directly targeting YY1. PMID- 27663661 TI - Lysosome-associated membrane proteins-1 and -2 (LAMP-1 and LAMP-2) assemble via distinct modes. AB - Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) have a large, heavily glycosylated luminal domain composed of two subdomains, and are the most abundant protein components in lysosome membranes. LAMP-1 and LAMP-2 have distinct functions, and the presence of both proteins together is required for the essential regulation of autophagy to avoid embryonic lethality. However, the structural aspects of LAMP-1 and LAMP-2 have not been elucidated. In the present study, we demonstrated that the subdomains of LAMP-1 and LAMP-2 adopt the unique beta-prism fold, similar to the domain structure of the dendritic cell-specific LAMP (DC-LAMP, LAMP-3), confirming the conserved aspect of this family of lysosome-associated membrane proteins. Furthermore, we evaluated the effects of the N-domain truncation of LAMP-1 or LAMP-2 on the assembly of LAMPs, based on immunoprecipitation experiments. We found that the N-domain of LAMP-1 is necessary, whereas that of LAMP-2 is repressive, for the organization of a multimeric assembly of LAMPs. Accordingly, the present study suggests for the first time that the assembly modes of LAMP-1 and LAMP-2 are different, which may underlie their distinct functions. PMID- 27663662 TI - The power of OMICs. AB - Over the past two decades, the field of systems biology, which encompasses the numerous, widely popular "OMICs" approaches, has driven many significant advances in biomedical research, enabling researchers to generate huge datasets at multiple levels of biological organization. Despite such successes, some scientists still think that "OMICs"-based research introduces a lot of chaos into the biomedical field and claim that the resultant data are often not reproducible and do not reveal deep mechanistic aspects of biological processes. In this editorial, I argue the following: first, that "OMICs" technologies have improved significantly to yield much better datasets; and second, that follow-up studies on components identified in "OMICs" analyses have yielded many valuable biological insights. PMID- 27663663 TI - Overexpression of SOX18 correlates with accelerated cell growth and poor prognosis in human pancreatic ductal adenocarcinoma. AB - Transcription factor SOX18 has been proved to play a significant role in carcinogenesis. However, no investigation was performed about the expression of SOX18 in pancreatic ductal adenocarcinoma (PDAC). In our work, we found that the PDAC tissues had higher level of SOX18 mRNA and protein expression than matched non-tumor pancreatic tissues and high level of SOX18 protein indicated poor prognosis for PDAC patients. After knockdown of SOX18 gene in PANC-1 and SW1990 cell lines, which showed higher expression level of SOX18 among five PDAC cell lines, the abilities of proliferation, migration and invasion were inhibited and the tumor growth was suppressed in vivo. In addition, the flow cytometry results indicated that down-regulation of SOX18 induced G1/S phase arrest. Furthermore, we found that the expression of cyclin D1, c-myc and MMP-7, three tumorigenesis promoters, was inhabited with downregulation of SOX18. In conclusion, our study reveals that SOX18 plays a significant role in promoting the growth of PDAC, and might serve as a promising target for PDAC therapy. PMID- 27663664 TI - Overexpression of ZIC5 promotes proliferation in non-small cell lung cancer. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) has become the leading cause of cancer-related deaths. It is therefore urgent that we identify new molecular targets to help cure NSCLC patients. Here, we identified ZIC5 as a potential novel oncogene. METHODS: We detected the expression of ZIC5 in tumor and normal tissues of NSCLC patients using quantitative real-time PCR and explored its clinical appearance. We then knocked down ZIC5 to observe changes in NSCLC cell proliferation and metastasis. Nude mouse xenograft models were established to measure ZIC5's function in vivo. RESULTS: Our results revealed that ZIC5 was expressed at dramatically higher levels in NSCLC tumor tissues than in normal tissues. High levels of ZIC5 expression were associated with a higher primary tumor grade. ZIC5 expression was significantly inhibited by small interfering RNA. After silencing ZIC5, the metastatic capacity of NSCLC cells was clearly lower. Knocking down ZIC5 significantly inhibited the proliferation of NSCLC cells, causing the cell cycle to be arrested in G2 phase. Xenograft tumor models showed that knocking down ZIC5 also inhibited tumor growth in vivo. Q-PCR and western blot analysis revealed that ZIC5 expression was closely associated with CCNB1 and CDK1 complex expression, while other cell cycle-related genes showed no significant correlation with ZIC5. CONCLUSIONS: Our experiment show that ZIC5 is highly upregulated in NSCLC tumor tissues and suggest that ZIC5 may act as an oncogene by influencing CCNB1 and CDK1 complex expression. ZIC5 may therefore be a potential biomarker and therapeutic target for NSCLC patients. PMID- 27663665 TI - A conserved glycine residue in the C-terminal region of human ATG9A is required for its transport from the endoplasmic reticulum to the Golgi apparatus. AB - ATG9A is the only polytopic protein of the mammalian autophagy-related protein family whose members regulate autophagosome formation during macroautophagy. At steady state, ATG9A localizes to several intracellular sites, including the Golgi apparatus, endosomes and the plasma membrane, and it redistributes towards autophagosomes upon autophagy induction. Interestingly, the transport of yeast Atg9 to the pre-autophagosomal structure depends on its self-association, which is mediated by a short amino acid motif located in the C-terminal region of the protein. Here, we investigated whether the residues that align with this motif in human ATG9A (V515-C519) are also required for its trafficking in mammalian cells. Interestingly, our findings support that human ATG9A self-interacts as well, and that this process promotes transport of ATG9A molecules through the Golgi apparatus. Furthermore, our data reveal that the transport of ATG9A out of the ER is severely impacted after mutation of the conserved V515-C519 motif. Nevertheless, the mutated ATG9A molecules could still interact with each other, indicating that the molecular mechanism of self-interaction differs in mammalian cells compared to yeast. Using sequential amino acid substitutions of glycine 516 and cysteine 519, we found that the stability of ATG9A relies on both of these residues, but that only the former is required for efficient transport of human ATG9A from the endoplasmic reticulum to the Golgi apparatus. PMID- 27663666 TI - Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop. AB - The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context. PMID- 27663667 TI - The temporal window of valuation is constricted among adolescent smokers. AB - Healthy decisions are associated with valuation of the future whereas unhealthy decisions are associated with devaluation of the future. Comparisons of future discounting of delayed rewards in adolescent smokers and non-smokers have been equivocal and past discounting of monetary gains has not been reported in adolescents. Here, adolescents completed future and past delay discounting tasks. A mixed-model analysis of covariance using a model with the lowest Bayesian Information Criterion revealed that adolescents discount the past more than the future and smokers discount more than non-smokers. These results suggest that adolescent smokers have a constricted temporal window, which may lead to disadvantageous decisions. PMID- 27663668 TI - Delay discounting of gains and losses, glycemic control and therapeutic adherence in type 2 diabetes. AB - OBJECTIVE: Delay discounting is the tendency to prefer smaller, sooner rewards to larger, later ones. Poor adherence in type 2 diabetes could be partially explained by a discounted value of health, as a function of delay. Delay discounting can be described with a hyperbolic model characterized by a coefficient, k. The higher k, the less future consequences are taken into account when making decisions. This study aimed to determine whether k would be correlated with glycated hemoglobin and adherence in type 2 diabetes. METHODS: Ninety-three patients were recruited in two diabetology departments. Delay discounting coefficients were measured with a computerized task. HbA1c was recorded and adherence was assessed by questionnaires. Potential socio demographic and clinical confounding factors were collected. RESULTS: There was a positive correlation between delay discounting of gains and HbA1c (r=0.242, P=0.023). This association remained significant after adjusting for potential confounding factors (F=4.807, P=0.031, eta2=0.058). This association was partially mediated by adherence to medication (beta=0.048, 95% CI [0.004-0.131]). CONCLUSIONS: Glycemic control is associated with delay discounting in patients suffering from type 2 diabetes. Should these findings be replicated with a prospective design, they could lead to new strategies to improve glycemic control among these patients. PMID- 27663669 TI - Natural acquired group B Streptococcus capsular polysaccharide and surface protein antibodies in HIV-infected and HIV-uninfected children. AB - Group B Streptococcus (GBS) is a major cause of invasive disease in young infants and also in older immunocompromised individuals, including HIV-infected persons. We compared naturally acquired antibody titres to GBS polysaccharide and surface protein antigens in HIV-uninfected and HIV-infected children aged 4-7 years. A multiplex Luminex immunoassay was used to measure IgG concentrations against GBS capsular polysaccharides (CPS) for serotypes Ia, Ib, III and V; and also extracellular localizing proteins which included cell-wall anchored proteins: Fibrinogen binding surface Antigen (FbsA), GBS Immunogenic Bacterial Adhesin (BibA), Surface immunogenic protein (Sip), gbs0393, gbs1356, gbs1539, gbs0392; and lipoproteins gbs0233, gbs2106 and Foldase PsrA. HIV-infected children (n=68) had significantly lower IgG GMT compared to HIV-uninfected (n=77) children against CPS of serotype Ib (p=0.012) and V (p=0.0045), and surface proteins Sip (p<0.001) and gbs2106 (p=0.0014). IgG GMT against GBS surface proteins: FbsA, gbs1539, gbs1356, gbs0392, gbs0393 and Foldase PsrA were significantly higher in HIV-infected children (p<0.004). Moreover, amongst HIV infected children, IgG GMT to GBS surface proteins were higher in those with CD4+ lymphocyte counts <500cell/MUL compared to those who had CD4+ lymphocyte count ?500cell/MUL with the exception of Sip. The increased susceptibility to invasive GBS disease in HIV infected individuals could be due to the lower serotype specific capsular antibody and possibly due to lower antibody to some of the GBS proteins such as Sip and gbs2106. PMID- 27663670 TI - Breastfeeding linked to the reduction of both rotavirus shedding and IgA levels after Rotarix(r) immunization in Mexican infants. AB - We examined potential risk factors on vaccine virus shedding and antibody seroresponse to human rotavirus vaccine (Rotarix) in Mexican infants. Two doses of Rotarix were administered to infants during the first two visits for their routine childhood immunization (~8 and 15weeks of age) in Mexico City. Infant's characteristics and socioeconomic indicators were obtained, including history of long-term feeding practices (exclusively/predominantly breastfed and exclusively/predominantly non-breastfed). Two serum specimens were collected, one during the second rotavirus vaccine visit and one 7weeks later. Stool specimens were collected between days 4-7 after each of the two rotavirus vaccine doses. Rotavirus IgA and IgG titers in serum were determined by enzyme immunoassays (EIA) and rotavirus shedding in stool was assessed by EIA and confirmed by RT PCR. The overall rotavirus IgA geometric mean titers (GMT) increased significantly post dose 2 from post dose 1 [176 (95%CI: 113-273) to 335 (238 471); p=0.020). Infants who were exclusively/predominantly breastfed were less likely to shed vaccine virus in stool than those who were formula-fed (22% vs. 43%, p=0.016). Infants who were breastfed had lower rotavirus IgA titers than those who were formula-fed after dose 1 [GMT: 145 (84-250) vs. 267 (126-566) p=0.188] and dose 2 [236 (147-378) vs.578 (367-910), p=0.007]. Infants who shed vaccine virus post dose 1 had significantly higher serum IgA GMT than those who did not shed [425 (188-965) vs. 150 (84-266), p=0.038]. Breastfeeding was linked with the reduction of both stool vaccine shedding, and IgA seroresponse. The reduced rotavirus replication in the gut and shedding after dose 1 may explain in part the lower IgA response in serum. PMID- 27663671 TI - Mono- and quadri-subtype virus-like particles (VLPs) containing H10 subtype elicit protective immunity to H10 influenza in a ferret challenge model. AB - Avian-origin influenza represents a global public health concern. In 2013, the H10N8 virus caused documented human infections for the first time. Currently, there is no approved vaccine against H10 influenza. Recombinant virus-like particles (VLPs) represent a promising vaccine approach. In this study, we evaluated H10 VLPs containing hemagglutinin from H10N8 virus as an experimental vaccine in a ferret challenge model. In addition, we evaluated quadri-subtype VLPs co-localizing H5, H7, H9 and H10 subtypes. Both vaccines elicited serum antibody that reacted with the homologous H10 derived from H10N8 virus and cross reacted with the heterologous H10N1 virus. Quadri-subtype vaccine also elicited serum antibody to the homologous H5, H7, and H9 antigens and cross-reacted with multiple clades of H5N1 virus. After heterologous challenge with the H10N1 virus, all vaccinated ferrets showed significantly reduced titers of replicating virus in the respiratory tract indicating protective effect of vaccination with either H10 VLPs or with quadri-subtype VLPs. PMID- 27663673 TI - MOZ (KAT6A) is essential for the maintenance of classically defined adult hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) are conventionally thought to be at the apex of a hierarchy that produces all mature cells of the blood. The quintessential property of these cells is their ability to reconstitute the entire hematopoietic system of hemoablated recipients. This characteristic has enabled HSCs to be used to replenish the hematopoietic system of patients after chemotherapy or radiotherapy. Here, we use deletion of the monocytic leukemia zinc finger gene (Moz/Kat6a/Myst3) to examine the effects of removing HSCs. Loss of MOZ in adult mice leads to the rapid loss of HSCs as defined by transplantation. This is accompanied by a reduction of the LSK-CD48-CD150+ and LSK-CD34-Flt3- populations in the bone marrow and a reduction in quiescent cells in G0 Surprisingly, the loss of classically defined HSCs did not affect mouse viability, and there was no recovery of the LSK-CD48-CD150+ and LSK-CD34-Flt3- populations 15 to 18 months after Moz deletion. Clonal analysis of myeloid progenitors, which produce short lived granulocytes, demonstrate that these are derived from cells that had undergone recombination at the Moz locus up to 2 years earlier, suggesting that early progenitors have acquired extended self-renewal. Our results establish that there are essential differences in HSC requirement for steady-state blood cell production compared with the artificial situation of reconstitution after transplantation into a hemoablated host. A better understanding of steady-state hematopoiesis may facilitate the development of novel therapies engaging hematopoietic cell populations with previously unrecognized traits, as well as characterizing potential vulnerability to oncogenic transformation. PMID- 27663672 TI - Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. AB - Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon alpha/beta receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation. PMID- 27663674 TI - Human CalDAG-GEFI deficiency increases bleeding and delays alphaIIbbeta3 activation. AB - Affinity regulation of integrin alphaIIbbeta3 for fibrinogen by inside-out signaling plays a critical role in hemostasis. Calcium and diacylglycerol (DAG) regulated guanine nucleotide exchange factor I (CalDAG-GEFI) was identified as a Rap1-activating molecule, and its role in inside-out alphaIIbbeta3 activation was established in CalDAG-GEFI-deficient mice. However, little information regarding CalDAG-GEFI in human platelets is available. Here, we report a 16-year-old girl with CalDAG-GEFI deficiency who has been suffering from severe bleeding tendency. Although talin and kindlin-3 were normally detected, CalDAG-GEFI was undetectable in her platelets by western blotting. Genetic analysis revealed compound heterozygous CalDAG-GEFI mutations, Lys309X and Leu360del, which were responsible for CalDAG-GEFI deficiency. The functional analysis demonstrated impaired alphaIIbbeta3 activation by various agonists except for phorbol myristate acetate, normal calcium mobilization, and impaired Rap1 activation, which were consistent with the phenotype of CalDAG-GEFI-deficient mice. Despite substantial alphaIIbbeta3 activation at high agonist concentrations, she had severe bleeding tendency. Further functional analysis demonstrated markedly delayed alphaIIbbeta3 activation velocity and decreased shear-induced thrombus formation. Contrary to CalDAG-GEFI-deficient mice, which showed integrin-dependent neutrophil functional abnormality, neutrophil beta2 integrin activation was not impaired in the patient. Our results demonstrate the critical role of CalDAG-GEFI in rapid alphaIIbbeta3 activation of human platelets. PMID- 27663675 TI - Cardiac involvement in Erdheim-Chester disease: an MRI study. PMID- 27663676 TI - The Slav-cleft: A three-center study of the outcome of treatment of cleft lip and palate. Part 1: Craniofacial morphology. AB - Results of a comparison of the outcomes of treatment of cleft lip and palate can be affected by growth characteristics of populations from which subjects with the clefts are derived. Moreover, conventional cephalometric techniques used in cleft studies for analysis of facial morphology provide only a partial description of shape and are confounded by biases regarding the reference structures. In this retrospective comparison, craniofacial morphology of preadolescent patients with unilateral cleft lip and palate treated in Warsaw (n = 35, age = 10.6 years, SD = 1.2), Prague (n = 38, age = 11.6 years, SD = 1.4), and Bratislava (n = 26, age = 10.5 years, SD = 1.6) were evaluated on cephalograms with the cephalometric method used in the Eurocleft study and geometric morphometrics. We found that patients treated in Warsaw showed slightly more favorable outcomes than in Prague and Bratislava. The differences were related primarily to the position of maxillary alveolar process, cranial base, mandibular angle, and soft tissues. Although no association between a component of treatment protocol and the outcome was found, it is possible that organizational factors such as participation of high-volume, experienced surgeons contributed to these results. PMID- 27663677 TI - Implant-prosthetic rehabilitation of hemimaxillectomy defects with CAD/CAM suprastructures. AB - BACKGROUND: Patients with hemimaxillectomy defects after tumor surgery can alternatively be rehabilitated with dental obturators or microvascular flaps. When general medical or oncologic conditions do not permit microvascular surgery, dental obturators are the only solution, yet retention for edentulous patients is often poor. The aim of this study was to evaluate whether CAD/CAM suprastructures supported by implants placed in both residual alveolar ridges and contralateral zygomatic bone could enhance obturator stability and improve functional outcomes. MATERIALS AND METHODS: Five edentulous patients with class IId hemimaxillectomy defects were included in the study. Implant-retained reconstructions were planned to support cross-arch CAD/CAM milled suprastructures. Patients had to rate their restorations on a 100-mm visual analogue scale before and after treatment. Additional evaluation was performed using the Oral Health Impact Profile (OHIP EDENT) questionnaire. RESULTS: In the 5 patients, 7 conventional implants were placed in the remaining zygomatic bone and 16 in the remaining contralateral alveolar ridge. After 4 months of submerged healing, CAD/CAM suprastructures were fabricated that connected all respective implants with each other. All of the prosthetic restorations were removable and bar-retained. They all achieved good defect closure and showed significant improvements concerning general satisfaction (p = 0.0343), stability (p < 0.0001), ability to chew (p = 0.0077), esthetics (p = 0.0173) and foreign body sensation (p = 0.0207). According to the OHIP-EDENT questionnaire (p = 0.0036) the improvements were significant. During the observation period of 29.4 months, no mechanical or biological complications occurred. CONCLUSION: The CAD/CAM suprastructures improved retention in all treated patients without any complications. PMID- 27663679 TI - Molecular characterization of a bactericidal permeability-increasing protein/lipopolysaccharide-binding protein from black rockfish (Sebastes schlegelii): Deciphering its putative antibacterial role. AB - Bactericidal permeability-increasing protein (BPI)/lipopolysaccharide (LPS) binding proteins (LBPs) are well-known proteins that play an indispensable role in host antimicrobial defense. Herein, we report a homolog of BPI/LBP from black rockfish (Sebastes schlegelii) (designated as RfBPI/LBP) and characterize its structural and functional features at the molecular level. We identified the putative complete open reading frame (1422 bp) of RfLBP that encodes a 474 amino acid protein with a predicted molecular mass of ~51.5 kDa. The primary protein sequence of RfBPI/LBP contains domain features of BPI/LBP family proteins and shares significant sequence consistency with its homologs. Our phylogenetic analysis clearly demonstrated the vertebrate ancestral origin of RfBPI/LBP, further reinforcing its evolutionary relationship with teleostean homologs. Recombinant RfBPI/LBP demonstrated in vitro LPS-binding activity and antibacterial activity against Escherichia coli, but not against Streptococcus iniae. Moreover, RfBPI/LBP exhibited temporal transcriptional activation against pathogens and pathogen-associated molecular patterns. Collectively, our findings suggest that RfBPI/LBP plays an essential role in host antimicrobial defense, plausibly through selective eradication of invading bacteria. PMID- 27663680 TI - Molecular characterisation, evolution and expression analysis of g-type lysozymes in Ciona intestinalis. AB - Lysozyme is an important defense molecule of the innate immune system. Known for its bactericidal properties, lysozyme catalyzes the hydrolysis of b-(1,4) glycosidic bonds between the N-acetyl glucosamine and N-acetyl muramic acid in the peptidoglycan layer of bacterial cell walls. In this study, the complete coding sequence of four g-type lysozymes were identified in Ciona intestinalis. Phylogenetic analysis and modelling supported the hypothesis of a close relationship with the vertebrate g-type lysozymes suggesting that the C. intestinalis g-type lysozyme genes (CiLys-g1, Cilys-g2, CiLys-g3, CiLys-g4) share a common ancestor in the chordate lineage. Protein motif searches indicated that C. intestinalis g-type lysozymes contain a GEWL domain with a GXXQ signature, typical of goose lysozymes. Quantitative Real-Time PCR analysis results showed that transcripts are expressed in various tissues from C. intestinalis. In order to determine the involvement of C. intestinalis g-type lysozymes in immunity, their expression was analyzed in the pharynx, showing that transcripts were significantly up-regulated in response to a challenge with lipopolysaccharide (LPS). These data support the view that CiLys g-type are molecules with potential for immune defense system against bacterial infection. PMID- 27663678 TI - Cost effectiveness of intermittent screening followed by treatment versus intermittent preventive treatment during pregnancy in West Africa: analysis and modelling of results from a non-inferiority trial. AB - BACKGROUND: Emergence of high-grade sulfadoxine-pyrimethamine (SP) resistance in parts of Africa has led to growing concerns about the efficacy of intermittent preventive treatment of malaria during pregnancy (IPTp) with SP. The incremental cost-effectiveness of intermittent screening and treatment (ISTp) with artemether lumefantrine (AL) as an alternative strategy to IPTp-SP was estimated followed by a simulation of the effects on cost-effectiveness of decreasing efficacy of IPTp SP due to SP resistance. The analysis was based on results from a multi-centre, non-inferiority trial conducted in West Africa. METHODS: A decision tree model was analysed from a health provider perspective. Model parameters for all trial countries with appropriate ranges and distributions were used in a probabilistic sensitivity analysis. Simulations were performed in hypothetical cohorts of 1000 pregnant women who received either ISTp-AL or IPTp-SP. In addition a cost consequences analysis was conducted. Trial estimates were used to calculate disability-adjusted-life-years (DALYs) for low birth weight and severe/moderate anaemia (both shown to be non-inferior for ISTp-AL) and clinical malaria (inferior for ISTp-AL). Cost estimates were obtained from observational studies, health facility costings and public procurement databases. Results were calculated as incremental cost per DALY averted. Finally, the cost-effectiveness changes with decreasing SP efficacy were explored by simulation. RESULTS: Relative to IPTp-SP, delivering ISTp-AL to 1000 pregnant women cost US$ 4966.25 more (95 % CI US$ 3703.53; 6376.83) and led to a small excess of 28.36 DALYs (95 % CI -75.78; 134.18), with LBW contributing 81.3 % of this difference. The incremental cost-effectiveness ratio was -175.12 (95 % CI -1166.29; 1267.71) US$/DALY averted. Simulations show that cost-effectiveness of ISTp-AL increases as the efficacy of IPTp-SP decreases, though the specific threshold at which ISTp AL becomes cost-effective depends on assumptions about the contribution of bed nets to malaria control, bed net coverage and the willingness-to-pay threshold used. CONCLUSIONS: At SP efficacy levels currently observed in the trial settings it would not be cost-effective to switch from IPTp-SP to ISTp-AL, mainly due to the substantially higher costs of ISTp-AL and limited difference in outcomes. The modelling results indicate thresholds below which IPT-SP efficacy must fall for ISTp-AL to become a cost-effective option for the prevention of malaria in pregnancy. PMID- 27663681 TI - The effect of telepsychiatric modalities on reduction of readmissions in psychiatric settings: A systematic review. AB - Introduction Telepsychiatric modalities are used widely in the treatment of many mental illnesses. It has also been proposed that telepsychiatric modalities could be a way to reduce readmissions. The purpose of the study was to conduct a systematic review of the literature on the effects of telepsychiatric modalities on readmissions in psychiatric settings. Methods We conducted a systematic literature search in MEDLINE, CINAHL, Embase, Cochrane, PsycINFO and Joanna Briggs databases in October 2015. Inclusion criteria were (a) patients with a psychiatric diagnosis, (b) telepsychiatric interventions and (c) an outcome related to readmission. Results The database search identified 218 potential studies, of which eight were eligible for the review. Studies were of varying quality and there was a tendency towards low-quality studies (five studies) which found positive outcomes regarding readmission, whereas the more methodological sound studies (three studies) found no effect of telepsychiatric modalities on readmission rates. Discussion Previous studies have proven the effectiveness of telepsychiatric modalities in the treatment of various mental illnesses. However, in the present systematic review we were unable to find an effect of telepsychiatric modalities on the rate of readmission. Some studies found a reduced rate of readmissions, but the poor methodological quality make the findings questionable. At the present time there is no evidence to support the use of telepsychiatry due to heterogeneous interventions, heterogeneous patient groups and lack of high-quality studies. PMID- 27663682 TI - Asking different questions: research priorities to improve the quality of care for every woman, every child. PMID- 27663683 TI - Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells. AB - At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity. Here, we found that ADA2 binds to neutrophils, monocytes, NK cells and B cells that do not express CD26, a receptor for ADA1. Moreover, the analysis of CD4+ T-cell subset revealed that ADA2 specifically binds to regulatory T cells expressing CD39 and lacking the receptor for ADA1. Also, it was found that ADA1 binds to CD16- monocytes, while CD16+ monocytes preferably bind ADA2. A study of the blood samples from ADA2-deficient patients showed a dramatic reduction in the number of lymphocyte subsets and an increased concentration of TNF-alpha in plasma. Our results suggest the existence of a new mechanism, where the activation and survival of immune cells is regulated through the activities of ADA2 or ADA1 anchored to the cell surface. PMID- 27663684 TI - Identification and characterization of a fusarium head blight resistance gene TaACT in wheat QTL-2DL. AB - Fusarium head blight (FHB) resistance in wheat is considered to be polygenic in nature. Cell wall fortification is one of the best resistance mechanisms in wheat against Fusarium graminearum which causes FHB. Metabolomics approach in our study led to the identification of a wide array of resistance-related (RR) metabolites, among which hydroxycinnamic acid amides (HCAAs), such as coumaroylagmatine and coumaroylputrescine, were the highest fold change RR metabolites in the rachis of a resistant near-isogenic line (NIL-R) upon F. graminearum infection. Placement of these metabolites in the secondary metabolic pathway led to the identification of a gene encoding agmatine coumaroyl transferase, herein referred to as TaACT, as a candidate gene. Based on wheat survey sequence, TaACT was located within a FHB quantitative trait loci on chromosome 2DL (FHB QTL-2DL) between the flanking markers WMC245 and GWM608. Phylogenetic analysis suggested that TaACT shared closest phylogenetic relationship with an ACT ortholog in barley. Sequence analysis of TaACT in resistant and susceptible NILs, with contrasting levels of resistance to FHB, led to the identification of several single nucleotide polymorphisms (SNPs) and two inversions that may be important for gene function. Further, a role for TaACT in FHB resistance was functionally validated by virus induced gene silencing (VIGS) in wheat NIL-R and based on complementation studies in Arabidopsis with act mutant background. The disease severity, fungal biomass and RR metabolite analysis confirmed TaACT as an important gene in wheat FHB QTL 2DL, conferring resistance to F. graminearum. PMID- 27663685 TI - Imaging complement by phase-plate cryo-electron tomography from initiation to pore formation. AB - Phase plates in cryo-electron tomography (cryoET) improve contrast, increasing the ability to discern separate molecules and molecular complexes in dense biomolecular environments. Here, we applied this new technology to the activation of the human complement system. Binding of C1 to antigen-antibody complexes initiates a cascade of proteolytic events that deposits molecules onto adjacent surfaces and terminates with the formation of membrane-attack-complex (MAC) pores in the targeted membranes. We imaged steps in this process using a Volta phase plate mounted on a Titan Krios equipped with a Falcon-II direct electron detector. The data show patches of single-layer antibodies on the surface and C1 bound to antibody platforms, with ca. ~4% of instances where C1r and C1s proteases have dissociated from C1, and potentially instances of C1 transiently interacting with its substrate C4 or product C4b. Next, extensive deposition of C4b and C3b molecules is apparent, although individual molecules cannot always be properly distinguished with the current methods. Observations of MAC pores include formation of both single and composite pores, and instances of potential soluble-MAC dissociation upon failure of membrane insertion. Overall, application of the Volta phase plate cryoET markedly improved the contrast in the tomograms, which allowed for individual components to be more readily interpreted. However, variability in the phase shift induced by the phase-plate during the course of an experiment, together with incomplete sampling during tomogram acquisition, limited the interpretability of the resulting tomograms. Our studies exemplify the potential in studying molecular processes with complex spatial topologies by phase-plate cryoET. PMID- 27663687 TI - Altered differentiation of enteric neural crest-derived cells from endothelin receptor-B null mouse model of Hirschsprung's disease. AB - PURPOSE: Hirschsprung's disease (HD) is caused by a failure of enteric neural crest-derived cells (ENCC) to colonize the bowel, resulting in an absence of the enteric nervous system (ENS). Previously, we developed a Sox10 transgenic version of the Endothelin receptor-B (Ednrb) mouse to visualize ENCC with the green fluorescent protein, Venus. The aim of this study was to isolate Sox10-Venus+ cells, which are differentiated neurons and glial cells in the ENS, and analyze these cells using Sox10-Venus mice gut. METHODS: The mid-and hindgut of Sox10 Venus+/Ednrb +/+ and Sox10-Venus+/Ednrb -/- at E13.5 and E15.5 were dissected and cells were dissociated. Sox10-Venus+ cells were then isolated. Expression of PGP9.5 and GFAP were evaluated neurospheres using laser scanning microscopy. RESULTS: 7 days after incubation, Sox10-Venus+ cells colonized the neurosphere. There were no significant differences in PGP9.5 expressions on E13.5 and E15.5. GFAP was significantly increased in HD compared to controls on E15.5 (P < 0.05). CONCLUSIONS: Our results suggest increased glial differentiation causes an imbalance in ENCC lineages, leading to a disruption of normal ENS development in this HD model. Isolation of ENCC provides an opportunity to investigate the ENS with purity and might be a useful tool for modeling cell therapy approaches to HD. PMID- 27663688 TI - Rectal mucosal/submucosal biopsy under general anesthesia ensures optimum diagnosis of bowel motility disorders. AB - PURPOSE: We reviewed all rectal mucosal/submucosal biopsies (RMSBx) performed between 1986 and 2015 focusing on specimen quality, incidence of complications during and after biopsy, and parental satisfaction. METHODS: From 1986 to 2004, RMSBx were performed without general anesthesia (GA) (N-GA; n = 98) and from 1995 to 2015 were performed under GA (GA; n = 525). In GA cases, some sections were stained intraoperatively and examined by a pathologist and pediatric surgeon immediately to identify ganglion cells. RESULTS: Mean ages at RMSBx were similar (2.7 vs. 2.5 years; p = NS). There were significantly more inadequate specimens in N-GA [18/98 (18.4 %) vs. 0/525 (0 %); p < 0.0001]. Incidence of rectal bleeding requiring transfusion was significantly lower in GA [0/525 (0 %) versus 2/98 (2.0 %); p = 0.024]. Parents of GA subjects willingly consented to RMSBx when told GA would facilitate diagnosis. Incidentally, RMSBx was more expensive in GA (US$1320 versus US$294; using Y120 = US$1). CONCLUSION: RMSBx performed under GA are safe and all specimens obtained included submucosa appropriate for optimum diagnosis in all the cases. PMID- 27663689 TI - Downregulation of Forkhead box F1 gene expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia. AB - PURPOSE: High mortality and morbidity in infants born with congenital diaphragmatic hernia (CDH) are attributed to pulmonary hypoplasia and pulmonary hypertension (PH). Forkhead box (Fox) transcription factors are known to be crucial for cell proliferation and homeostasis. FoxF1 is essential for lung morphogenesis, vascular development, and endothelial proliferation. Mutations in FoxF1 and also the Fox family member FoxC2 have been identified in neonates with PH. In human and experimental models of arterial PH, the Fox protein FoxO1 was found to be downregulated. We hypothesized that Fox expression is altered in the lungs of the nitrofen-induced CDH rat model and investigated the expression of FoxF1, FoxC2, and FoxO1. METHODS: Following ethical approval (Rec 913b), time pregnant Sprague-Dawley rats received nitrofen or vehicle on gestational day (D9). Fetuses were sacrificed on D21, inspected for CDH and divided into CDH (n = 11) and control group (n = 11). Gene expression of FoxF1, FoxC2, and FoxO1 was evaluated with qRT-PCR. Detected alterations of mRNA levels were subsequently assessed on the protein level by performing western blot analysis and laser scanning confocal microscopy. RESULTS: The relative mRNA level of FoxF1 was significantly downregulated in CDH lungs compared to controls (FoxF1 CDH 1.047 +/ 0.108, FoxF1 Ctrl 1.419 +/- 0.01, p = 0.014). Relative mRNA levels of FoxC2 and FoxO1 were not found to be altered between the experimental groups (FoxC2 CDH 30.74 +/- 8.925, FoxC2 Ctrl 27.408 +/- 7.487, p = 0.776; FoxO1 CDH 0.011 +/- 0.002, FoxO1 Ctrl 0.011 +/- 0.001, p = 0.809). On the protein level, western blotting demonstrated a reduced pulmonary protein expression of FoxF1 in CDH lungs. Confocal microscopy showed a markedly diminished expression of FoxF1 in the pulmonary vasculature of CDH lungs compared to controls. CONCLUSION: Our study demonstrates a strikingly reduced expression of FoxF1 in the pulmonary vasculature of nitrofen-induced CDH. Altered FoxF1 gene expression during embryogenesis may participate in vascular maldevelopment resulting in PH in this animal model. PMID- 27663690 TI - Subset selective search on the basis of color and preview. AB - In the preview paradigm observers are presented with one set of elements (the irrelevant set) followed by the addition of a second set among which the target is presented (the relevant set). Search efficiency in such a preview condition has been demonstrated to be higher than that in a full-baseline condition in which both sets are simultaneously presented, suggesting that a preview of the irrelevant set reduces its influence on the search process. However, numbers of irrelevant and relevant elements are typically not independently manipulated. Moreover, subset selective search also occurs when both sets are presented simultaneously but differ in color. The aim of the present study was to investigate how numbers of irrelevant and relevant elements contribute to preview search in the absence and presence of a color difference between subsets. In two experiments it was demonstrated that a preview reduced the influence of the number of irrelevant elements in the absence but not in the presence of a color difference between subsets. In the presence of a color difference, a preview lowered the effect of the number of relevant elements but only when the target was defined by a unique feature within the relevant set (Experiment 1); when the target was defined by a conjunction of features (Experiment 2), search efficiency as a function of the number of relevant elements was not modulated by a preview. Together the results are in line with the idea that subset selective search is based on different simultaneously operating mechanisms. PMID- 27663691 TI - Can We Foster a Culture of Peer Support and Promote Mental Health in Adolescence Using a Web-Based App? A Control Group Study. AB - BACKGROUND: Adolescence with its many transitions is a vulnerable period for the development of mental illnesses. Establishing effective mental health promotion programs for this age group is a challenge crucial to societal health. Programs must account for the specific developmental tasks that adolescents face. Considering peer influence and fostering adolescent autonomy strivings is essential. Participation in a program should be compelling to young people, and their affinity to new technologies offers unprecedented opportunities in this respect. OBJECTIVE: The Companion App was developed as a Web-based app giving adolescents access to a peer mentoring system and interactive, health-relevant content to foster a positive peer culture among adolescents and thereby strengthen social support and reduce stress. METHODS: In a control group study design, a group of employed (n=546) and unemployed (n=73) adolescents had access to the Companion App during a 10-month period. The intervention was evaluated using a combination of quantitative and qualitative approaches. Linear mixed effects models were used to analyze changes in chronic stress levels and perception of social support. Monthly feedback on the app and qualitative interviews at the end of the study allowed for an in-depth exploration of the adolescents' perception of the intervention. RESULTS: Adolescents in the intervention group did not use the Companion App consistently. The intervention had no significant effect on chronic stress levels or the perception of social support. Adolescents reported endorsing the concept of the app and the implementation of a peer mentoring system in particular. However, technical difficulties and insufficiently obvious benefits of using the app impeded more frequent usage. CONCLUSIONS: The Companion Project implemented a theory-driven and innovative approach to mental health promotion in adolescence, taking into account the specifics of this developmental phase. Particularities of the implementation context, technical aspects of the app, and insufficient incentives may have played considerable roles concerning the difficulties of the Companion Project to establish commitment. However, adopting peer mentoring as a strategy and using an app still seems to us a promising approach in mental health promotion in adolescents. Future projects should be careful to invest enough resources into the technical development of an app and consider a large use of incentives to establish commitment. When targeting risk groups, such as unemployed adolescents, it may be expedient to use more structured approaches including face-to-face support. PMID- 27663692 TI - How Does Cholecystectomy Influence Recurrence of Idiopathic Acute Pancreatitis? AB - BACKGROUND: Idiopathic acute pancreatitis is diagnosed in approximately 10-30 % of cases of acute pancreatitis. While there is evidence to suggest that the cause in many of these patients is microlithiasis, this fact has not been translated into a resource efficient treatment strategy that is proven to reduce recurrence rates. The aim of this study was to examine the value of prophylactic cholecystectomy following an episode of acute pancreatitis in patients with no history of alcohol abuse and no stones found on ultrasound. METHODS: This was a retrospective study of 2236 patients who presented to a regional Australian hospital. Patients were included when diagnosed with acute pancreatitis with no confirmed cause. Recurrence of acute pancreatitis was compared between those that did and did not undergo cholecystectomy. RESULTS: One hundred ninety-five consecutive patients met the study definition of "idiopathic" acute pancreatitis. 33.8 % (66/195) underwent cholecystectomy. The patients who had cholecystectomy had a recurrence rate of 19.7 % (13/66) whereas, of those managed expectantly, 42.8 % (68/159) had at least one recurrence of acute pancreatitis (P = 0.001). CONCLUSIONS: Following an episode of acute pancreatitis with no identifiable cause, in patients fit for surgery, cholecystectomy should be considered to reduce the risk of recurrent episodes of pancreatitis. PMID- 27663693 TI - Transcatheter Arterial Embolization for Hepatic Arterial Injury Related to Percutaneous Transhepatic Portal Intervention. AB - PURPOSE: To assess the usefulness of transcatheter arterial embolization (TAE) for the hepatic arterial injury related to percutaneous transhepatic portal intervention (PTPI). MATERIALS AND METHODS: Fifty-four patients, 32 males and 22 females with a median age of 68 years (range 43-82 years), underwent PTPI. The procedures consisted of 33 percutaneous transhepatic portal vein embolizations, 19 percutaneous transhepatic variceal embolizations, and 2 percutaneous transhepatic portal venous stent placements. Two patients with gastric varices underwent percutaneous transhepatic variceal embolization twice because of recurrence. Therefore, the total number of procedures was 56. Among them, hepatic arterial injury occurred in 6 PTPIs in 5 patients, and TAE was performed. We assessed technical success, complications related to TAE, and clinical outcome. Technical success was defined as the disappearance of findings due to hepatic arterial injury on digital subtraction angiography. RESULTS: As hepatic arterial injuries, 4 extravasations and 2 arterioportal shunts developed. All TAEs were performed successfully. The technical success rate was 100 %. Complication of TAE occurred in 5 of 6 TAEs; 3 were focal liver infarction, not requiring further treatment, and 2 were biloma that required percutaneous drainage. Five TAEs in 4 patients were performed immediately after the PTPI, and these 4 patients were alive. However, one TAE was performed 10 h later, and the patient died due to multiple organ failure 2 months later although TAE was successful. CONCLUSION: TAE is a useful treatment for hepatic arterial injury related to PTPI. However, it should be performed at an early stage. PMID- 27663694 TI - Mainstream capnography system for nonintubated children in the postanesthesia care unit: Performance with changing flow rates, and a comparison to side stream capnography. AB - INTRODUCTION: Monitoring of exhaled carbon dioxide (CO2 ) in nonintubated patients is challenging. We compared the precision of a mainstream mask capnography to side stream sampling nasal cannula capnography. In addition, we compared the effect of gas flow rates on the measured exhaled CO2 between mainstream mask and side stream nasal cannula capnography. METHODS: A mainstream mask capnography system (cap-ONE) was tested. Children (weight of 7-40 kg, ASA 1 2) following anesthesia for minor procedures were assigned randomly to side stream or mainstream sampling groups. The side stream group wore a nasal cannula with CO2 side port (NC). In the postanesthesia care unit, O2 flow was started at 5 l.min-1 , reduced to 2 and then 0.25 l.min-1 every 3 min. Capnogram analysis measuring heights of all the waveforms was performed for continuous 120 s from the end of recording at each O2 flow rate for each group. RESULTS: Fifty-eight children were enrolled and 39 were analyzed (18 side stream NC and 21 mainstream mask). There were two mouth breathing children excluded from study in side stream NC group due to failure to capture measurable CO2 waveforms. Peak CO2 values measured by mainstream mask system were normally (Gaussian) distributed with smaller standard deviation (sd) at each O2 flow than were those measured by side stream NC system which demonstrated irregular distributions with larger sd. Peak CO2 values measurement was less affected by a change in flow rate in mainstream mask group than in side stream NC group (P = 0.04 in 5-0.25 l.min-1 O2 flow change). CONCLUSION: A new mainstream mask system (cap-ONE) performed with greater precision than side stream NC monitoring regardless of mouth breathing. Measurement of peak CO2 values by mainstream mask system showed normal distribution with smaller standard deviation (sd) and was less affected by O2 flow change in predictable fashion. PMID- 27663695 TI - A cost or a benefit? Counterintuitive effects of diet quality and cadmium in Lymnaea stagnalis. AB - Diet quality can have a strong impact on organismal fitness although diet quality is infrequently considered as a factor in toxicity tests. The purpose of this study was to assess how diets differing in nutritional content affect sensitivity to Cd as measured by several sublethal responses related directly to bioenergetics. We evaluated feeding rate, growth rate, behavior and macronutrient content in the pond snail Lymnaea stagnalis exposed to Cd and fed two different diets. Hatchlings were fed either lettuce or high-caloric pellets, and exposed to 5, 10, and 20 ug/L Cd for 12 days. Length and weight were measured at the beginning and end of the test. The amount of food eaten and behavior were determined every two days. Total lipids, proteins and carbohydrates were biochemically measured at test end. For the second part of the study, snails were fed either lettuce or pellets for 2 weeks and then exposed to high challenge concentrations of Cd. Growth coefficients based on length and weight were significantly higher for snails fed pellets. In addition, snails exposed to Cd had significantly smaller growth coefficients than those in the control for both diets. Total carbohydrates and lipids were higher for snails fed pellets while the protein content was not significantly affected by Cd or diets. Even though snails fed pellets grew significantly faster, contrary to expectations they were significantly more sensitive to Cd compared to those fed lettuce. This study provides evidence that a bioenergetics-based approach can been used to better understand how diet can affect the ecotoxicity of chemical stressors to freshwater gastropods. PMID- 27663696 TI - The association between follicle stimulating hormone and glutathione peroxidase activity is dependent on abdominal obesity in postmenopausal women. AB - PURPOSE: Menopause is frequently associated with an increase in visceral fat, thus modifying redox status by promoting oxidative damage and decreasing antioxidant defense systems. It is known that at higher concentrations estradiol has some antioxidant properties, while its decline in postmenopause is associated with pro-oxidant effects. However, the role of follicle stimulating hormone (FSH) in antioxidant defense in postmenopausal women is still not well elucidated. Therefore, we aimed to evaluate the potential complex association between visceral obesity, FSH and enzymatic antioxidant defense as measured by glutathione peroxidase (GPx) in postmenopausal women. METHODS: A total of 150 postmenopausal women (mean age 56.6 +/- 4.8 years), among them 50 normal weight and 100 overweight/obese, were included. GPx activity, FSH, luteinizing hormone, estradiol, total testosterone, cardiometabolic and anthropometric parameters, were determined. RESULTS: With increasing tertiles of serum FSH levels, significant increase in GPx activity (P = 0.005) was found. Also, the highest number of overweight/obese subjects were in the group with the lowest FSH values (chi 2 = 14.9, P < 0.001). After multiple linear regression analysis, the relationship between GPx and FSH disappeared, whereas only higher waist circumference (beta = -0.218, P = 0.045) predicted lower FSH level (adjusted R 2 = 0.227). CONCLUSION: Higher GPx activity is associated with higher FSH level, but abdominal obesity may be the underlying determinant of this relationship. PMID- 27663697 TI - Placement of a microdialysis catheter during laparoscopic rectal cancer surgery to assess anastomotic leak. PMID- 27663698 TI - A systematic review of the management of anal fistula in infants. AB - BACKGROUND: Fistula-in-ano (FIA) in infants differs, in several ways, from FIA in adults. The current review aims to assess FIA in infants less than 2 years old and to illustrate the outcome of different treatment modalities described in the literature. METHODS: An organized search of the English literature over the past 25 years was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Electronic databases and Google Scholar were searched for articles focusing on management of FIA in infants. RESULTS: Fourteen studies were eligible for this review. Variables analyzed comprised patient characteristics, type of FIA, methods of treatment, recurrence, and postoperative complications. The studies included comprised total of 490 infants, 89 % of them less than 1 year old. Most patients (97.5 %) were males with a median age of 7 months. Around 20 % of patients with FIA underwent conservative treatment initially, and 73 % of them achieved complete resolution. Surgery was performed on 86 % of the infants. Fistulotomy accounted for 65 % of the procedures performed and was associated with a higher recurrence rate than fistulectomy (6.6 vs. 1.1 %, respectively). Complications of surgical management occurred in 2.6 % of the patients. FIA typically occurs in male infants, mainly under 1 year of age. Almost all fistulae in this age group are low. CONCLUSIONS: The majority of the studies reviewed evaluated surgical treatment of FIA. However, the few studies that employed conservative treatment reported complete resolution of FIA in most infants. Fistulotomy was the most commonly performed surgery for FIA and was associated with fewer complications, yet a higher recurrence rate than fistulectomy. PMID- 27663699 TI - Integrating Entropy-Based Naive Bayes and GIS for Spatial Evaluation of Flood Hazard. AB - Regional flood risk caused by intensive rainfall under extreme climate conditions has increasingly attracted global attention. Mapping and evaluation of flood hazard are vital parts in flood risk assessment. This study develops an integrated framework for estimating spatial likelihood of flood hazard by coupling weighted naive Bayes (WNB), geographic information system, and remote sensing. The north part of Fitzroy River Basin in Queensland, Australia, was selected as a case study site. The environmental indices, including extreme rainfall, evapotranspiration, net-water index, soil water retention, elevation, slope, drainage proximity, and density, were generated from spatial data representing climate, soil, vegetation, hydrology, and topography. These indices were weighted using the statistics-based entropy method. The weighted indices were input into the WNB-based model to delineate a regional flood risk map that indicates the likelihood of flood occurrence. The resultant map was validated by the maximum inundation extent extracted from moderate resolution imaging spectroradiometer (MODIS) imagery. The evaluation results, including mapping and evaluation of the distribution of flood hazard, are helpful in guiding flood inundation disaster responses for the region. The novel approach presented consists of weighted grid data, image-based sampling and validation, cell-by-cell probability inferring and spatial mapping. It is superior to an existing spatial naive Bayes (NB) method for regional flood hazard assessment. It can also be extended to other likelihood-related environmental hazard studies. PMID- 27663700 TI - Divergent cAMP signaling differentially regulates serotonin-induced spinal motor plasticity. AB - Spinal metabotropic serotonin receptors encode transient experiences into long lasting changes in motor behavior (i.e. motor plasticity). While interactions between serotonin receptor subtypes are known to regulate plasticity, the significance of molecular divergence in downstream G protein coupled receptor signaling is not well understood. Here we tested the hypothesis that distinct cAMP dependent signaling pathways differentially regulate serotonin-induced phrenic motor facilitation (pMF); a well-studied model of spinal motor plasticity. Specifically, we studied the capacity of cAMP-dependent protein kinase A (PKA) and exchange protein activated by cAMP (EPAC) to regulate 5-HT2A receptor-induced pMF within adult male rats. Although spinal PKA, EPAC and 5-HT2A each elicit pMF when activated alone, concurrent PKA and 5-HT2A activation interact via mutual inhibition thereby blocking pMF expression. Conversely, concurrent EPAC and 5-HT2A activation enhance pMF expression reflecting additive contributions from both mechanisms. Thus, we demonstrate that distinct downstream cAMP signaling pathways enable differential regulation of 5-HT2A-induced pMF. Conditional activation of independent signaling mechanisms may explain experience amendable changes in plasticity expression (i.e. metaplasticity), an emerging concept thought to enable flexible motor control within the adult central nervous system. PMID- 27663702 TI - Radiographic assessment of degenerative lumbar spinal stenosis: is MRI superior to CT? AB - OBJECTIVE: To determine the reliability and dependability of magnetic resonance imaging (MRI) and computerized tomography (CT) in the assessment of lumbar spinal stenosis and correlate the qualitative assessment to both a quantitative assessment and functional outcome measures. Multiple studies have addressed the issue of CT and MRI imaging in lumbar spinal stenosis. None showed superiority of one modality. METHODS: We performed a standardized qualitative and quantitative review of CT and MRI scans of 54 patients. Intra-observer and inter-observer reliability was determined between three reviewer using Kappa coefficient. Agreement between the two modalities was analyzed. ODI and SF-36 outcomes were correlated with the imaging assessments. RESULTS: Almost perfect intra-observer reliability for MRI was achieved by the two expert reviewers (kappa = 0.91 for surgeon and kappa = 0.92 for neuro-radiologist). For CT, substantial intra observer agreement was found for the surgeon (kappa = 0.77) while the neuro radiologist was higher (kappa = 0.96). For both CT and MRI the standardized qualitative assessment used by the two expert reviewers had a better inter observer reliability than that between the expert reviewers and the general reporting radiologist, who did not utilize a standardized assessment system. When the qualitative assessment was compared directly, CT overestimated the degree of stenosis 20-35 % of the time (p < 0.05) while MRI overestimated the degree of stenosis 2-11 % of the time (p < 0.05). No correlation was found between qualitative and quantitative analysis with functional status. CONCLUSIONS: This study directly demonstrates that MRI is a more reliable tool than CT, but neither correlates with functional status. Both experience of the reader and the standardization of a qualitative assessment are influential to the reliability. PMID- 27663701 TI - Structure and symmetry inform gating principles of ionotropic glutamate receptors. AB - Ionotropic glutamate receptors (iGluRs) transduce signals derived from release of the excitatory neurotransmitter glutamate from pre-synaptic neurons into excitation of post-synaptic neurons on a millisecond time-scale. In recent years, the elucidation of full-length iGluR structures of NMDA, AMPA and kainate receptors by X-ray crystallography and single particle cryo-electron microscopy has greatly enhanced our understanding of the interrelationships between receptor architecture and gating mechanism. Here we briefly review full-length iGluR structures and discuss the similarities and differences between NMDA receptors and non-NMDA iGluRs. We focus on distinct conformations, including ligand-free, agonist-bound active, agonist-bound desensitized and antagonist-bound conformations as well as modulator and auxiliary protein-bound states. These findings provide insights into structure-based mechanisms of iGluR gating and modulation which together shape the amplitude and time course of the excitatory postsynaptic potential. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 27663704 TI - A Novel Intestine Model Apparatus for Drug Dissolution Capable of Simulating the Peristaltic Action. AB - A novel dissolution apparatus has been proposed as an alternative apparatus for dissolution testing. In this study, we evaluated the performance of the new intestine model for simulating the peristaltic action (IMSPA), generating the movement that closely mimics peristaltic contractions of the small intestine. Two polyethylene oxide matrix tablet formulations, containing a model drug belonging to class III of the Biopharmaceutics Classification System, were tested. Dissolution was also performed in the USP2 apparatus. The release profiles were further compared to the in vivo data to evaluate the in vivo relevance of the new apparatus. The results demonstrated that the novel apparatus showed good discriminatory power between different polyethylene oxide formulations. Moreover, a better relation to the in vivo data was established by the IMSPA as compared to the USP2 apparatus. In conclusion, the model parameters were efficiently controlled to ensure the dissolution conditions crucial for evaluating the in vivo release performance of the tested formulations. PMID- 27663705 TI - Effect of organic loading rate on dark fermentative hydrogen production in the continuous stirred tank reactor and continuous mixed immobilized sludge reactor from waste pastry hydrolysate. AB - Waste pastry (6%, w/v) was hydrolyzed by the produced glucoamylase and protease to obtain the glucose (19.8g/L) and free amino nitrogen (179mg/L) solution. Then, the effect of organic loading rate (OLR) (8-40kgCOD/(m3d)) on dark fermentative hydrogen production in the continuous stirred tank reactor (CSTR) and continuous mixed immobilized sludge reactor (CMISR) from waste pastry hydrolysate was investigated and compared. The maximum hydrogen production rate of CSTR (277.76mL/(hL)) and CMISR (320.2mL/(hL)) were achieved at OLR of 24kgCOD/(m3d) and 32kgCOD/(m3d), respectively. Carbon recovery ranged from 75.2-84.1% in the CSTR and CMISR with the balance assumed to be converted to biomass. One gram waste pastry could produce 0.33g (1.83mmol) glucose which could be further converted to 79.24mL (3.54mmol) hydrogen in the CMISR or 91.66mL (4.09mmol) hydrogen in the CSTR. This is the first study which reports dark fermentative hydrogen production from waste pastry. PMID- 27663703 TI - A Call to Revisit the Prenatal Period as a Focus for Action Within the Reproductive and Perinatal Care Continuum. AB - Objectives The broad maternal and child health community has witnessed increased attention to the entire continuum of reproductive and perinatal health concerns over the past few years. However, both recent discouraging trends in prenatal care access and utilization and a renewed understanding of prenatal care as a critical anchor of the reproductive/perinatal health continuum for women who do get pregnant demand a new effort to focus on the prenatal period as a gateway for maternal and infant health. Methods This commentary: describes the Medicaid expansions and the momentum for universal access to prenatal care of the 1980 1990s; examines the pivot away from this goal and its aftermath; provides a rationale for why renewed attention to prenatal care and the prenatal period is essential; and, explores the potential focus of an updated prenatal care agenda. Conclusion We conclude that increasing women's access to high quality prenatal care will require substantial effort at the clinical, community, policy, and system levels. Only when attention is paid to all phases of the reproductive/perinatal health continuum with an emphasis on continuity between all periods, and on the social determinants that affect health and well-being, will our nation be able to ensure the health of all women across the life course (whether or not they ever become mothers), while simultaneously fulfilling our nation's promise that all children-no matter their income or race/ethnicity-will have the opportunity to be born well. PMID- 27663706 TI - Assessment of health-care waste management in a humanitarian crisis: A case study of the Gaza Strip. AB - Health-care waste management requires technical, financial and human resources, and it is a challenge for low- and middle income countries, while it is often neglected in protracted crisis or emergency situations. Indeed, when health, safety, security or wellbeing of a community is threatened, solid waste management usually receives limited attention. Using the Gaza Strip as the case study region, this manuscript reports on health-care waste management within the context of a humanitarian crisis. The study employed a range of methods including content analyses of policies and legislation, audits of waste arisings, field visits, stakeholder interviews and evaluation of treatment systems. The study estimated a production from clinics and hospitals of 683kg/day of hazardous waste in the Gaza Strip, while the total health-care waste production was 3357 kg/day. A number of challenges was identified including lack of clear definitions and regulations, limited accurate data on which to base decisions and strategies and poor coordination amongst key stakeholders. Hazardous and non-hazardous waste was partially segregated and treatment facilities hardly used, and 75% of the hazardous waste was left untreated. Recommendations for mitigating these challenges posed to patients, staff and the community in general are suggested. The outputs are particularly useful to support decision makers, and re-organize the system according to reliable data and sound assumptions. The methodology can be replicated in other humanitarian settings, also to other waste flows, and other sectors of environmental sanitation. PMID- 27663707 TI - A review on automated sorting of source-separated municipal solid waste for recycling. AB - A crucial prerequisite for recycling forming an integral part of municipal solid waste (MSW) management is sorting of useful materials from source-separated MSW. Researchers have been exploring automated sorting techniques to improve the overall efficiency of recycling process. This paper reviews recent advances in physical processes, sensors, and actuators used as well as control and autonomy related issues in the area of automated sorting and recycling of source-separated MSW. We believe that this paper will provide a comprehensive overview of the state of the art and will help future system designers in the area. In this paper, we also present research challenges in the field of automated waste sorting and recycling. PMID- 27663708 TI - A degradation model for high kitchen waste content municipal solid waste. AB - Municipal solid waste (MSW) in developing countries has a high content of kitchen waste (KW), and therefore contains large quantities of water and non hollocellulose degradable organics. The degradation of high KW content MSW cannot be well simulated by the existing degradation models, which are mostly established for low KW content MSW in developed countries. This paper presents a two-stage anaerobic degradation model for high KW content MSW with degradations of hollocellulose, sugars, proteins and lipids considered. The ranges of the proportions of chemical compounds in MSW components are summarized with the recommended values given. Waste components are grouped into rapidly or slowly degradable categories in terms of the degradation rates under optimal water conditions for degradation. In the proposed model, the unionized VFA inhibitions of hydrolysis/acidogenesis and methanogenesis are considered as well as the pH inhibition of methanogenesis. Both modest and serious VFA inhibitions can be modeled by the proposed model. Default values for the parameters in the proposed method can be used for predictions of degradations of both low and high KW content MSW. The proposed model was verified by simulating two laboratory experiments, in which low and high KW content MSW were used, respectively. The simulated results are in good agreement with the measured data of the experiments. The results show that under low VFA concentrations, the pH inhibition of methanogenesis is the main inhibition to be considered, while the inhibitions of both hydrolysis/acidogenesis and methanogenesis caused by unionized VFA are significant under high VFA concentrations. The model is also used to compare the degradation behaviors of low and high KW content MSW under a favorable environmental condition, and it shows that the gas potential of high KW content MSW releases more quickly. PMID- 27663709 TI - An arsenate-reducing and alkane-metabolizing novel bacterium, Rhizobium arsenicireducens sp. nov., isolated from arsenic-rich groundwater. AB - A novel arsenic (As)-resistant, arsenate-respiring, alkane-metabolizing bacterium KAs 5-22T, isolated from As-rich groundwater of West Bengal was characterized by physiological and genomic properties. Cells of strain KAs 5-22T were Gram-stain negative, rod-shaped, motile, and facultative anaerobic. Growth occurred at optimum of pH 6.0-7.0, temperature 30 degrees C. 16S rRNA gene affiliated the strain KAs 5-22T to the genus Rhizobium showing maximum similarity (98.4 %) with the type strain of Rhizobium naphthalenivorans TSY03bT followed by (98.0 % similarity) Rhizobium selenitireducens B1T. The genomic G + C content was 59.4 mol%, and DNA-DNA relatedness with its closest phylogenetic neighbors was 50.2 %. Chemotaxonomy indicated UQ-10 as the major quinone; phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol as major polar lipids; C16:0, C17:0, 2-OH C10:0, 3-OH C16:0, and unresolved C18:1 omega7C/omega9C as predominant fatty acids. The cells were found to reduce O2, As5+, NO3-, SO42- and Fe3+ as alternate electron acceptors. The strain's ability to metabolize dodecane or other alkanes as sole carbon source using As5+ as terminal electron acceptor was supported by the presence of genes encoding benzyl succinate synthase (bssA like) and molybdopterin-binding site (mopB) of As5+ respiratory reductase (arrA). Differential phenotypic, chemotaxonomic, genotypic as well as physiological properties revealed that the strain KAs 5-22T is separated from its nearest recognized Rhizobium species. On the basis of the data presented, strain KAs 5 22T is considered to represent a novel species of the genus Rhizobium, for which the name Rhizobium arsenicireducens sp. nov. is proposed as type strain (=LMG 28795T=MTCC 12115T). PMID- 27663710 TI - Contributing factors and outcomes of treatment refusal in pediatric oncology in Germany. PMID- 27663712 TI - Proceedings of the RAMI Section of OtoRhinoLaryngology Head and Neck Surgery (ORL HNS) Winter Meeting, Friday 11th December 2015, Education and Research Centre, Royal Victoria Eye and Ear Hospital, Adelaide Road, Dublin 2. PMID- 27663713 TI - Proceedings of the RAMI Section of OtoRhinoLaryngology Head and Neck Surgery (ORL HNS) Spring Meeting, Saturday 23rd April 2016, Sheraton Hotel, Athlone, Co. Westmeath. PMID- 27663711 TI - Prevalence of celiac disease in Indian children with type 1 diabetes. AB - BACKGROUND: Type 1 diabetes (T1D) patients are at an increased risk of having celiac disease (CD). We evaluated the prevalence and clinical profile of CD in children and adolescents with T1D and reviewed the Indian literature to determine prevalence and reasons for variability. METHODS: In this cross-sectional study, subjects with T1D were prospectively evaluated with a demographic and gastrointestinal (GI) questionnaire, human IgA-tissue transglutaminase (IgA tTGA), and endoscopic duodenal biopsy in serology positive patients. Studies evaluating prevalence of CD in T1D from India were reviewed. RESULTS: Fourteen (13.6 %) of the 103 (52 boys, 13 years [2-20]) T1D patients were IgA-tTGA (182 U [47-300]) positive and 3.8 % (4/103) had villous atrophy on histology. Subjects with T1D and CD (n = 4) were younger at onset of T1D (32.5 +/- 12.6 vs. 110.5 +/- 53.8 months; p < 0.005) and more often had GI symptoms (pain abdomen [2/4 vs. 6/89; p = 0.01], stool frequency of 2-3/day [3/4 vs. 38/89; p = 0.004]) than screen negative T1D (n = 89). Growth and glycemic control were not different between the groups. In the 7 Indian studies involving 915 children and adults, 13.8 % (8 % to 17.8 %) T1D were serology positive. Prevalence of CD was reported as 6.9 % (2.3 % to 11.1 %), but only 3.1 % (2.3 % to 4.2 %) had villous atrophy on histology. CONCLUSIONS: Potential CD and CD were present in 13.6 % and 3.8 % children with T1D respectively. T1D with CD have onset of diabetes at younger age and were more often symptomatic than screen negative T1D. PMID- 27663715 TI - Endoscopic submucosal resection of gastric subepithelial lesions smaller than 20 mm: a comparison of saline solution-assisted snare and cap band mucosectomy techniques. AB - BACKGROUND AND AIMS: Application of endoscopic submucosal resection (ESMR) in the management of gastric subepithelial lesions (GSLs) less than 20 mm is gradually increasing because it allows diagnosis and treatment at the same operative session. In this study, we compare and evaluate the benefits of ESMR with an endoscopic cap band mucosectomy technique or saline solution-assisted snare technique in GSLs smaller than 20 mm. METHODS: This was a retrospective analysis of a prospectively maintained database used at 2 academic tertiary care centers. A total of 63 patients (34 females, mean age 52 years) with endoscopically resected GSLs were included in this study. RESULTS: The mean tumor size determined by EUS was 12.3 mm (range, 5-20 mm). Sixty-seven percent of the GSLs were localized in the antrum in all groups. The endoscopic cap band mucosectomy technique was used to resect 32 (50.8%) GSLs, whereas 31 (49.2%) were resected with the saline solution-assisted snare technique. The en bloc resection rates were 97% for the saline solution-assisted snare technique and 100% for the endoscopic cap band mucosectomy. Intraoperative bleeding occurred in 1 of 31 patients (3.2%) when ESMR was performed with the saline solution-assisted snare technique. Postoperative bleeding was seen in 1 of 32 patients (3.1%) who underwent the endoscopic cap band mucosectomy technique. CONCLUSIONS: In GSLs smaller than 20 mm, ESMR with saline solution-assisted snare or endoscopic cap band mucosectomy techniques is safe, the adverse event rate is low, accurate diagnosis is achieved, and treatment with en bloc resection is provided in a single session. Given similar success and adverse event rates, saline solution assisted ESMR may be the preferred technique because of its lower cost advantages. PMID- 27663716 TI - Distinct endoscopic characteristics of sessile serrated adenoma/polyp with and without dysplasia/carcinoma. AB - BACKGROUND AND AIMS: Sessile serrated adenoma/polyp (SSA/P) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSA/P can be difficult to detect. This study aimed to clarify the endoscopic characteristics of SSA/P with advanced histology. METHODS: We examined 462 endoscopically or surgically resected lesions that were pathologically diagnosed as SSA/P, including 414 without and 41 with cytologic dysplasia, and 7 with invasive carcinoma. We retrospectively studied the clinicopathologic and endoscopic characteristics and performed pit pattern analysis. RESULTS: A stepwise increase in the size of the SSA/P series was identified along with their dysplastic progression, although 19 of 48 (39.6%) SSA/Ps with dysplasia/carcinoma were <=10 mm in size. Most lesions were covered with a mucus cap. Macroscopically, (semi)pedunculated morphology, double elevation, central depression, and reddishness were found more frequently in SSA/P with cytologic dysplasia and invasive carcinoma ([semi]pedunculated morphology, 17.1%/28.6%; double elevation, 63.4%/57.1%; central depression, 9.8%/28.6%; reddishness, 39.0%/85.7%) than in those without dysplasia (4.6%, 4.6%, 3.9%, and 3.4%, respectively). Furthermore, the presence of at least 1 of these 4 markers had high sensitivity (91.7%) for identifying the dysplasia/carcinoma within a SSA/P, with a specificity of 85.3%. In the pit pattern analysis, all SSA/Ps without dysplasia exhibited type II pit pattern only, whereas 94.4% of SSA/Ps with dysplasia/carcinoma showed type II in addition to type IIIL, IV, VI, or VN pit patterns. CONCLUSIONS: In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, in addition to the use of magnifying endoscopy, may be useful to accurately diagnose advanced histology within an SSA/P. PMID- 27663714 TI - Long-term outcomes of per-oral endoscopic myotomy in patients with achalasia with a minimum follow-up of 2 years: an international multicenter study. AB - BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has shown promising safety and efficacy in short-term studies. However, long-term follow-up data are very limited. The aims of this study were to assess (1) clinical outcome of patients with a minimum post-POEM follow-up of 2 years and (2) factors associated with long-term clinical failure after POEM. METHODS: A retrospective chart review was performed that included all consecutive patients with achalasia who underwent POEM with a minimum follow-up of 2 years at 10 tertiary-care centers. Clinical response was defined by a decrease in Eckardt score to 3 or lower. RESULTS: A total of 205 patients (45.8% men; mean age, 49 years) were followed for a median of 31 months (interquartile range, 26-38 months). Of these, 81 patients (39.5%) had received previous treatment for achalasia before POEM. Clinical success was achieved in 98% (185/189), 98% (142/144), and 91% (187/205) of patients with follow-up within 6 months, at 12 months, and >=24 months, respectively. Of 185 patients with clinical response at 6 months, 11 (6%) experienced recurrent symptoms at 2 years. History of previous pneumatic dilation was associated with long-term treatment failure (odds ratio, 3.41; 95% confidence interval, 1.25 9.23). Procedure-related adverse events occurred in 8.2% of patients and only 1 patient required surgical intervention. Abnormal esophageal acid exposure and reflux esophagitis were documented in 37.5% and 18% of patients, respectively. However, these rates are simply a reference number among a very selective group of patients. CONCLUSIONS: POEM is safe and provides high initial clinical success and excellent long-term outcomes. Among patients with confirmed clinical response within 6 months, 6% had recurrent symptoms by 2 years. PMID- 27663717 TI - Phytosterols and Dementia. AB - As the aging of the world's population is becoming increasingly serious, dementia related diseases have become a hot topic in public health research. In recent years, human epidemiological studies have focused on lipid metabolism disorders and dementia. The efficacy of phytosterol intake as a cholesterol-lowering agent has been demonstrated. Phytosterols directly serve as ligands of the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), activating Sirtuin 1 (SIRT-1), which are involved in the regulation of lipid metabolism and the pathogenesis of dementia. Moreover, phytosterols mediate cell and membrane cholesterol efflux or beta amyloid (Abeta) metabolism, which have preventative and therapeutic effects on dementia. Additionally, incorporation of plant sterols in lipid rafts can effectively reduce dietary fat and alter the dietary composition of fiber, fat and cholesterol to regulate appetite and calories. Overall, the objectives of this review are to explore whether phytosterols are a potentially effective target for the prevention of dementia and to discuss a possible molecular mechanism by which phytosterols play a role in the pathogenesis of dementia via the PPARs-SIRT-1 pathway. PMID- 27663720 TI - The role of mouse 2',5'-oligoadenylate synthetase 1 paralogs. AB - The interferon-induced oligoadenylate synthetase (OAS) family is one of the most important immune response proteins to the viral infection. The OAS protein binds dsRNA and is activated to produce 2',5'-oligoadenylates, which lead to the activation of latent form of RNase L, resulting in degradation of cellular and viral RNA and inhibition of viral replication. In mice, the Oas gene family locates on chromosome 5. The mouse Oas gene locus undergoes a recent series of duplication event, leading to the presence of eight paralogs of Oas1 genes (Oas1a through Oas1h) that forms Oas gene cluster with the Oas2, Oas3 and two OasL (OasL1 and OasL2) genes. Previous studies demonstrated that the mouse Oas1b gene conferred resistance to the flavivirus infection in mice; however, the antiviral activity of other mouse Oas1 gene family is still unknown. Therefore, in the present study, we have evaluated the mouse Oas1 paralogs regarding the enzymatic activity and antiviral activity against the two neurotropic flaviviruses, West Nile virus and tick-borne encephalitis virus. The mouse Oas1 genes were cloned from C57BL/6J (B6) as well as the Oas1b derived from feral mouse strain, MSM. The obtained results demonstrated that only Oas1a and Oas1g showed enzymatic activity. Although MSM-derived Oas1b showed antiviral activity to both viruses, all B6-derived OAS paralogs did not show antiviral activity. These results suggest that Oas1a and Oas1g play a role in potentiating viral RNA-induced interferon response in the cell, whereas the Oas1b works as a specific anti flavivirus factor unless it is mutated. However, the role of other paralogs is unknown and should wait for further investigation. PMID- 27663719 TI - Comparative genome and evolutionary analysis of naturally occurring Beilong virus in brown and black rats. AB - Recently, we reported the presence of Beilong virus in spleen and kidney samples of brown rats and black rats, suggesting that these rodents could be natural reservoirs of Beilong virus. In this study, four genomes of Beilong virus from brown rats and black rats were sequenced. Similar to the Beilong virus genome sequenced from kidney mesangial cell line culture, those of J-virus from house mouse and Tailam virus from Sikkim rats, these four genomes from naturally occurring Beilong virus also contain the eight genes (3'-N-P/V/C-M-F-SH-TM-G-L 5'). In these four genomes, the attachment glycoprotein encoded by the G gene consists of 1046 amino acids; but for the original Beilong virus genome sequenced from kidney mesangial cell line, the G CDS was predicted to be prematurely terminated at position 2205 (TGG->TAG), resulting in a 734-amino-acid truncated G protein. This phenomenon of a lack of nonsense mutation in naturally occurring Beilong viruses was confirmed by sequencing this region of 15 additional rodent samples. Phylogenetic analyses showed that the cell line and naturally occurring Beilong viruses were closely clustered, without separation into subgroups. In addition, these viruses were further clustered with J-virus and Tailam virus, with high bootstrap supports of >90%, forming a distinct group in Paramyxoviridae. Brown rats and black rats are natural reservoirs of Beilong virus. Our results also supports that the recently proposed genus, Jeilongvirus, should encompass Beilong virus, J-virus and Tailam virus as members. PMID- 27663721 TI - G+C content differs in conserved and variable amino acid residues of flaviviruses and other evolutionary groups. AB - Flaviviruses are small RNA viruses that exhibit genetic and ecological diversity and a wide range of G+C content (GC%). We discovered that, amongst flaviviruses, the GC% of nucleotides encoding conserved amino acid (AA) residues was consistently higher than that of nucleotides encoding variable AAs. This intriguing phenomenon was also identified for a wide range of other viruses, and some non-viral evolutionary groups. Here, we analyse the possible mechanisms underlying this imbalanced nucleotide content (in particular the role of the specific G content and the AA composition in flaviviral genomes) and discuss its evolutionary implications. Our findings suggest that one of the most simple characteristics of the genetic code (i.e., the G or G+C content of codons) is linked with the evolutionary behavior of the corresponding encoded AAs. PMID- 27663718 TI - Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos. AB - OBJECTIVE: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. METHODS: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. RESULTS: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% overall (beta = 0.34 +/- 0.11% per allele; P = 0.002) and in women (beta = 0.41 +/- 0.14% per C-allele; P = 0.003), but not in men (beta = 0.28 +/- 0.18% per C-allele; P = 0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (beta = 0.054 +/- 0.018SD vs. beta = 0.008 +/- 0.011SD per C-allele; P = 0.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). CONCLUSIONS: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women. PMID- 27663722 TI - Fluctuations in glucose levels induce glial toxicity with glutamatergic, oxidative and inflammatory implications. AB - Astrocytes are dynamic cells that maintain brain homeostasis by regulating neurotransmitter systems, antioxidant defenses, inflammatory responses and energy metabolism. Astroglial cells are also primarily responsible for the uptake and metabolism of glucose in the brain. Diabetes mellitus (DM) is a pathological condition characterized by hyperglycemia and is associated with several changes in the central nervous system (CNS), including alterations in glial function. Classically, excessive glucose concentrations are used to induce experimental models of astrocyte dysfunction; however, hypoglycemic episodes may also cause several brain injuries. The main focus of the present study was to evaluate how fluctuations in glucose levels induce cytotoxicity. The culture medium of astroglial cells was replaced twice as follows: (1) from 6mM (control) to 12mM (high glucose), and (2) from 12mM to 0mM (glucose deprivation). Cell viability, mitochondrial function, oxidative/nitrosative stress, glutamate metabolism, inflammatory responses, nuclear factor kappaB (NFkappaB) transcriptional activity and p38 mitogen-activated protein kinase (p38 MAPK) levels were assessed. Our in vitro experimental model showed that up and down fluctuations in glucose levels decreased cell proliferation, induced mitochondrial dysfunction, increased oxidative/nitrosative stress with consequent cellular biomolecular damage, impaired glutamate metabolism and increased pro-inflammatory cytokine release. Additionally, activation of the NFkappaB and p38 signaling pathways were putative mechanisms of the effects of glucose fluctuations on astroglial cells. In summary, for the first time, we show that changes in glucose concentrations, from high-glucose levels to glucose deprivation, exacerbate glial injury. PMID- 27663724 TI - Zirconia abutments for single-tooth implant restorations: a 10- to 11-year follow up study. AB - OBJECTIVES: To evaluate the clinical outcome of custom-made zirconia abutments for implant-supported single-tooth restorations 10-11 years after insertion. MATERIAL AND METHODS: The study comprises a clinical examination of 23 patients with 30 restorations placed 10-11 years ago. Oral surgeons placed the implants. The prosthodontic treatment was provided at a prosthodontic specialist clinic. The restoration was either an all-ceramic crown for cementation or a screw retained one-piece restoration with the veneering porcelain baked directly to the zirconia abutment. Besides the clinical and radiographic examination at the 10- to 11-year follow-up, the patients' records were scrutinized regarding clinical and radiographic data from insertion of the restoration up to the last visit at the clinic. RESULTS: The zirconia abutments performed well. Both technical and biological complications were rare; most patients were in general extremely satisfied with the restorations. No all-ceramic crowns fractured during the observation period. One implant was lost after 51/2 years in service. There were no significant differences for changes in any of the soft tissue registrations or the peri-implant marginal bone level between the conventional two-piece abutment crown restoration and the one-piece restoration. The peri-implant bone level changes from placement to the clinical examination 10-11 years later were small (mean 0.26 mm, SD 0.6 mm). CONCLUSIONS: Zirconia abutments for single-implant crowns demonstrated excellent technical and biological results over 10-11 years of function, and most patients were extremely satisfied with the aesthetics and the function of their single-implant restorations. PMID- 27663723 TI - Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention after Kawasaki Disease: The Pediatric Canadian Series. AB - Coronary artery (CA) aneurysms are serious complications of Kawasaki disease (KD) responsible for ischemic events. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are reported with limited data on indications and comparative efficacy. Retrospective multicenter comparison of CA intervention following KD is performed in this study. Twenty two cases were available from 5 centers, of whom 11 underwent CABG, 10 PCI and 1 systemic thrombolysis. Age at intervention (8.3 +/- 3.9 vs 11.3 +/- 4.9 years, p = 0.14) and interval from diagnosis (5.6 +/- 4.1 vs 6.5 +/- 4.7 years, p = 0.64) were similar between CABG and PCI. Interventions were based on angiography in 15 patients or cardiac event in 7, with no difference between CABG and PCI (p = 0.24). Patients with CABG were more likely to undergo multivessel intervention (73 vs 10 %, p = 0.006). None of the patients needed reintervention after CABG, compared to 6 after PCI and 1 after systemic thrombolysis (p = 0.004). Signs of ischemia on stress testing or MIBI were present in 15 patients before intervention and persisted in 9 patients following last intervention, in a significantly higher proportion after CABG than PCI (80 vs 17 %, p = 0.01). In this series, CABG, which mostly involved multivessel intervention, was superior to PCI. Nevertheless, larger-scale studies may help define patient selection criteria for a beneficial PCI approach. PMID- 27663726 TI - Inverse liquid chromatography as a tool for characterisation of the surface layer of ceramic biomaterials. AB - The novel technique for ceramic biomaterials surface characterisation was proposed. The examined bone substitute materials were two orthophosphates: hydroxyapatite, beta-tricalcium phosphate and the mixture of these two - biphasic calcium phosphate. The aim of this work was characterisation of the ceramic biomaterials surface expressed via the values of parameters e, s, a, b, v considered in linear free energy relationship. The values of these parameters reflect the ability of stationary phase to occur in different types of interactions. The sorption phenomena occurring on the bone substitute materials surface are responsible for the process of the multiplication of the osteoblasts. Thus the detailed description of this phenomena may contribute to the better understanding of bone loss regeneration mechanism. The data required for characterisation by using LFER model was collected by means of inverse liquid chromatography with the use of five different mobile phases: 98% ethanol, ethanol/water (50/50), water, 0.2M NaCl and SBF. The determination of the ceramic orthophosphates surface properties in SBF solution allowed to observe the behaviour of biomaterials in "natural environment" - in living organism. PMID- 27663725 TI - A trait stacking system via intra-genomic homologous recombination. AB - MAIN CONCLUSION: A gene targeting method has been developed, which allows the conversion of 'breeding stacks', containing unlinked transgenes into a 'molecular stack' and thereby circumventing the breeding challenges associated with transgene segregation. A gene targeting method has been developed for converting two unlinked trait loci into a single locus transgene stack. The method utilizes intra-genomic homologous recombination (IGHR) between stably integrated target and donor loci which share sequence homology and nuclease cleavage sites whereby the donor contains a promoterless herbicide resistance transgene. Upon crossing with a zinc finger nuclease (ZFN)-expressing plant, double-strand breaks (DSB) are created in both the stably integrated target and donor loci. DSBs flanking the donor locus result in intra-genomic mobilization of a promoterless selectable marker-containing donor sequence, which can be utilized as a template for homology-directed repair of a concomitant DSB at the target locus resulting in a functional selectable marker via nuclease-mediated cassette exchange (NMCE). The method was successfully demonstrated in maize using a glyphosate tolerance gene as a donor whereby up to 3.3 % of the resulting progeny embryos cultured on selection medium regenerated plants with the donor sequence integrated into the target locus. The process could be extended to multiple cycles of trait stacking by virtue of a unique intron sequence homology for NMCE between the target and the donor loci. This is the first report that describes NMCE via IGHR, thereby enabling trait stacking using conventional crossing. PMID- 27663727 TI - Separation and quantification of silver nanoparticles and silver ions using reversed phase high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry in combination with isotope dilution analysis. AB - A reversed phase high performance liquid chromatography coupled to an inductively coupled plasma mass spectrometer (HPLC-ICP-MS) approach in combination with isotope dilution analysis (IDA) for the separation and parallel quantification of nanostructured and ionic silver (Ag) is presented. The main focus of this work was the determination of the ionic Ag concentration. For a sufficient stabilization of the ions without dissolving the nanoparticles (NPs), the eluent had to be initially optimized. The determined Ag ion concentration was in a good agreement with results obtained using ultrafiltration. Further, the mechanism of the NP separation in the HPLC column was investigated. Typical size exclusion effects were found by comparing results from columns with different pore sizes. Since the recovery rates decreased with increasing Ag NP size and large Ag NPs did not elute from the column, additional interactions of the particles with the stationary phase were assumed. Our results reveal that the presented method is not only applicable to Ag NPs, but also to gold and polystyrene NPs. Finally, IDA HPLC-ICP-MS experiments in single particle mode were performed to determine the particle cut-off size. The comparison with conventional spICP-MS experiments resulted in a similar diameter and particle size distribution. PMID- 27663728 TI - Designing monoclonal antibody fragment-based affinity resins with high binding capacity by thiol-directed immobilisation and optimisation of pore/ligand size ratio. AB - Monoclonal antibody (mAb) based affinity resins usually suffer from low binding capacity, most probably as a result of steric hindrance by the large 150kDa size of the mAb and a random immobilisation approach. The present work investigates the influence of a variety of factors on dynamic binding capacity (DBC) such as pore/ligand size ratio, accessibility of ligand and ligand density. The effect of pore/ligand size ratio was investigated using Fab and scFv fragments on various resins with different pore sizes. The accessibility of the ligand was investigated by a site-directed immobilisation approach, where three C-terminal tags, PPKPPK, FLAGTM and Cys, were introduced into the Fab fragments for immobilisation on resins via amino-, carboxyl- and thiol-groups, respectively. The scFv fragments were tagged at the C-terminal only with FLAGTM to enable a straight forward purification procedure, and were immobilised to resins via amino and carboxyl-groups. The target protein had a molecular weight (MW) of 50kDa. A 3-fold higher dynamic binding capacity at 100% breakthrough (DBC100%) was observed for Fab wild-type (wt) on CNBr-activated Sepharose 4 FF relative to mAb on same resin at the same ligand density. However, no major difference in DBC100% was observed between Fab wt and scFv immobilised on CNBr-activated Sepharose 4 FF at the same ligand density. Thus, further increase of pore/ligand size ratio from Fab to scFv on a resin with average pore size of 300A, did not seem to be beneficial. Among the tested tags, only the C-terminal Cys tag proved to site direct the ligands during immobilisation as it allowed the DBC100% to increase 1.6-fold as compared to Fab wt immobilised via amino-groups on CNBr-activated Sepharose 4 FF and Actigel ALD Superflow at the same ligand density. The influence of ligand density was investigated by selecting immobilised Fab Cys on Sulfhydryl-reactive resin. Increasing ligand density from 0.103 to 0.202MUmol/mL resulted in the same utilisation yield (82-85%), whereas a further increase in ligand density from 0.202 to 0.328MUmol/mL resulted in a 20%-unit decrease in utilisation yield and less steep breakthrough curve, suggesting steric hindrance in the pores of the resin. In addition, site-directed affinity ligands resulted in a more pronounced, sigmoid-shaped breakthrough curve, leading to more efficient use of capacity. The highest DBC100% was obtained for Fab Cys on Sulfhydryl-reactive resin and scFv on Actigel ALD Superflow; 11mg/mL and 10mg/mL, respectively, as compared to the DBC100% of 0.8mg/mL for mAb on CNBr-activated Sepharose 4 FF. Pore/ligand size ratio of 3, which was achieved for Fab ligands on the studied resins, was shown to be feasible for capturing a protein in MW of 50kDa. Totally, a 13.8-fold improvement in DBC100% was achieved with the Fab based affinity resin coupled via the C-terminal Cys as compared to the mAb-based affinity resin. PMID- 27663729 TI - Visualizing small differences using subtractive chromatographic analysis. AB - Subtraction of chromatograms coming from two different samples collected under identical conditions can highlight small variations, serving as a useful tool for visualizing differences between experimental and control groups. While the basis for this general approach has been known for decades, the technique is seldom used in modern chromatographic analysis. We report an investigation into the application of subtractive chromatographic analysis in several areas of pharmaceutical research where detection of small differences between samples is important. Our investigation found that elimination of artifacts caused by peak misalignment was often necessary, especially for extremely sharp chromatographic peaks obtained in rapid injection MISER chromatography. Alignment of individual peaks prior to subtraction, combined with fast detector sampling rates, or data interpolation in cases where this is not possible, was found to afford convenient visualization of small differences (~1%) among samples, suggesting potential utility in high throughput screening of process adsorbents or other applications in pharmaceutical research and development. PMID- 27663730 TI - Genetic drivers of vulnerability and resistance in relapsed acute lymphoblastic leukemia. PMID- 27663732 TI - Residential emissions in Beijing: About 400 * 104 t. PMID- 27663731 TI - Improved i.p. drug delivery with bioadhesive nanoparticles. AB - The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space. BNPs loaded with a potent chemotherapeutic agent [epothilone B (EB)] showed significantly lower systemic toxicity and higher therapeutic efficacy against i.p. chemotherapy-resistant uterine serous carcinoma-derived xenografts compared with free EB and non-BNPs loaded with EB. PMID- 27663733 TI - Tightening the connection between transposable element mobilization and aging. PMID- 27663734 TI - Microvilli set the stage for T-cell activation. PMID- 27663735 TI - Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism. AB - We had reported elevated serum levels of the peptide neurotensin (NT) in children with autism spectrum disorders (ASD). Here, we show that NT stimulates primary human microglia, the resident immune cells of the brain, and the immortalized cell line of human microglia-SV40. NT (10 nM) increases the gene expression and release (P < 0.001) of the proinflammatory cytokine IL-1beta and chemokine (C-X-C motif) ligand 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 from human microglia. NT also stimulates proliferation (P < 0.05) of microglia-SV40. Microglia express only the receptor 3 (NTR3)/sortilin and not the NTR1 or NTR2. The use of siRNA to target sortilin reduces (P < 0.001) the NT-stimulated cytokine and chemokine gene expression and release from human microglia. Stimulation with NT (10 nM) increases the gene expression of sortilin (P < 0.0001) and causes the receptor to be translocated from the cytoplasm to the cell surface, and to be secreted extracellularly. Our findings also show increased levels of sortilin (P < 0.0001) in the serum from children with ASD (n = 36), compared with healthy controls (n = 20). NT stimulation of microglia-SV40 causes activation of the mammalian target of rapamycin (mTOR) signaling kinase, as shown by phosphorylation of its substrates and inhibition of these responses by drugs that prevent mTOR activation. NT-stimulated responses are inhibited by the flavonoid methoxyluteolin (0.1-1 MUM). The data provide a link between sortilin and the pathological findings of microglia and inflammation of the brain in ASD. Thus, inhibition of this pathway using methoxyluteolin could provide an effective treatment of ASD. PMID- 27663736 TI - Rational design of a Kv1.3 channel-blocking antibody as a selective immunosuppressant. AB - A variable region fusion strategy was used to generate an immunosuppressive antibody based on a novel "stalk-knob" structural motif in the ultralong complementary-determining region (CDR) of a bovine antibody. The potent Kv1.3 channel inhibitory peptides Moka1-toxin and Vm24-toxin were grafted into different CDRs of the humanized antibodies BVK and Synagis (Syn) using both beta sheet and coiled-coil linkers. Structure-activity relationship efforts led to generation of the fusion protein Syn-Vm24-CDR3L, which demonstrated excellent selectivity and potency against effector human memory T cells (subnanomolar to picomolar EC50 values). This fusion antibody also had significantly improved plasma half-life and serum stability in rodents compared with the parent Vm24 peptide. Finally, this fusion protein showed potent in vivo efficacy in the delayed type hypersensitivity in rats. These results illustrate the utility of antibody CDR fusions as a general and effective strategy to generate long-acting functional antibodies, and may lead to a selective immunosuppressive antibody for the treatment of autoimmune diseases. PMID- 27663737 TI - Integrated analysis of phenome, genome, and transcriptome of hybrid rice uncovered multiple heterosis-related loci for yield increase. AB - Hybrid rice is the dominant form of rice planted in China, and its use has extended worldwide since the 1970s. It offers great yield advantages and has contributed greatly to the world's food security. However, the molecular mechanisms underlying heterosis have remained a mystery. In this study we integrated genetics and omics analyses to determine the candidate genes for yield heterosis in a model two-line rice hybrid system, Liang-you-pei 9 (LYP9) and its parents. Phenomics study revealed that the better parent heterosis (BPH) of yield in hybrid is not ascribed to BPH of all the yield components but is specific to the BPH of spikelet number per panicle (SPP) and paternal parent heterosis (PPH) of effective panicle number (EPN). Genetic analyses then identified multiple quantitative trait loci (QTLs) for these two components. Moreover, a number of differentially expressed genes and alleles in the hybrid were mapped by transcriptome profiling to the QTL regions as possible candidate genes. In parallel, a major QTL for yield heterosis, rice heterosis 8 (RH8), was found to be the DTH8/Ghd8/LHD1 gene. Based on the shared allelic heterozygosity of RH8 in many hybrid rice cultivars, a common mechanism for yield heterosis in the present commercial hybrid rice is proposed. PMID- 27663738 TI - Inferring interaction partners from protein sequences. AB - Specific protein-protein interactions are crucial in the cell, both to ensure the formation and stability of multiprotein complexes and to enable signal transduction in various pathways. Functional interactions between proteins result in coevolution between the interaction partners, causing their sequences to be correlated. Here we exploit these correlations to accurately identify, from sequence data alone, which proteins are specific interaction partners. Our general approach, which employs a pairwise maximum entropy model to infer couplings between residues, has been successfully used to predict the 3D structures of proteins from sequences. Thus inspired, we introduce an iterative algorithm to predict specific interaction partners from two protein families whose members are known to interact. We first assess the algorithm's performance on histidine kinases and response regulators from bacterial two-component signaling systems. We obtain a striking 0.93 true positive fraction on our complete dataset without any a priori knowledge of interaction partners, and we uncover the origin of this success. We then apply the algorithm to proteins from ATP-binding cassette (ABC) transporter complexes, and obtain accurate predictions in these systems as well. Finally, we present two metrics that accurately distinguish interacting protein families from noninteracting ones, using only sequence data. PMID- 27663739 TI - O-fucosylated glycoproteins form assemblies in close proximity to the nuclear pore complexes of Toxoplasma gondii. AB - Toxoplasma gondii is an intracellular parasite that causes disseminated infections in fetuses and immunocompromised individuals. Although gene regulation is important for parasite differentiation and pathogenesis, little is known about protein organization in the nucleus. Here we show that the fucose-binding Aleuria aurantia lectin (AAL) binds to numerous punctate structures in the nuclei of tachyzoites, bradyzoites, and sporozoites but not oocysts. AAL also binds to Hammondia and Neospora nuclei but not to more distantly related apicomplexans. Analyses of the AAL-enriched fraction indicate that AAL binds O-linked fucose added to Ser/Thr residues present in or adjacent to Ser-rich domains (SRDs). Sixty-nine Ser-rich proteins were reproducibly enriched with AAL, including nucleoporins, mRNA-processing enzymes, and cell-signaling proteins. Two endogenous SRDs-containing proteins and an SRD-YFP fusion localize with AAL to the nuclear membrane. Superresolution microscopy showed that the majority of the AAL signal localizes in proximity to nuclear pore complexes. Host cells modify secreted proteins with O-fucose; here we describe the O-fucosylation pathway in the nucleocytosol of a eukaryote. Furthermore, these results suggest O fucosylation is a mechanism by which proteins involved in gene expression accumulate near the NPC. PMID- 27663740 TI - Symplastic signaling instructs cell division, cell expansion, and cell polarity in the ground tissue of Arabidopsis thaliana roots. AB - Cell-to-cell communication is essential for the development and patterning of multicellular organisms. In plants, plasmodesmata (PD) provide direct routes for intercellular signaling. However, the role that PD-mediated signaling plays in plant development has not been fully investigated. To gain a comprehensive view of the role that symplastic signaling plays in Arabidopsis thaliana, we have taken advantage of a synthetic allele of CALLOSE SYNTHASE3 (icals3m) that inducibly disrupts cell-to-cell communication specifically at PD. Our results show that loss of symplastic signaling to and from the endodermis has very significant effects on the root, including an increase in the number of cell layers in the root and a misspecification of stele cells, as well as ground tissue. Surprisingly, loss of endodermal signaling also results in a loss of anisotropic elongation in all cells within the root, similar to what is seen in radially swollen mutants. Our results suggest that symplastic signals to and from the endodermis are critical in the coordinated growth and development of the root. PMID- 27663741 TI - Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. AB - Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid. PMID- 27663744 TI - Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence. AB - Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle-related risk factors. Despite this intriguing pathogenic parallel, large-scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up-to-date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease. PMID- 27663743 TI - Oriented collagen fibers direct tumor cell intravasation. AB - In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (~10 mg/mL protein concentration). PMID- 27663742 TI - Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice. AB - Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and a leading genetic form of autism. The Fmr1 KO mouse, a model of FXS, exhibits elevated translation in the hippocampus and the cortex. ERK (extracellular signal-regulated kinase) and mTOR (mechanistic target of rapamycin) signaling regulate protein synthesis by activating downstream targets critical to translation initiation and elongation and are known to contribute to hippocampal defects in fragile X. Here we show that the effect of loss of fragile X mental retardation protein (FMRP) on these pathways is brain region specific. In contrast to the hippocampus, ERK (but not mTOR) signaling is elevated in the neocortex of fragile X mice. Phosphorylation of ribosomal protein S6, typically a downstream target of mTOR, is elevated in the neocortex, despite normal mTOR activity. This is significant in that S6 phosphorylation facilitates translation, correlates with neuronal activation, and is altered in neurodevelopmental disorders. We show that in fragile X mice, S6 is regulated by ERK via the "alternative" S6 kinase p90-ribosomal S6 kinase (RSK), as evidenced by the site of elevated phosphorylation and the finding that ERK inhibition corrects elevated RSK and S6 activity. These findings indicate that signaling networks are altered in the neocortex of fragile X mice such that S6 phosphorylation receives aberrant input from ERK/RSK. Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizures in fragile X mice. Our findings identify RSK as a therapeutic target for fragile X and suggest the therapeutic potential of drugs for the treatment of FXS may vary in a brain-region-specific manner. PMID- 27663745 TI - Exposure to Amphetamines Leads to Development of Amphetamine Type Stimulants Associated Cardiomyopathy (ATSAC). AB - With rapidly rising prevalence of exposure to Amphetamine Type Stimulants (ATS), novel insights into cardiotoxic effects of this substance are being presented in the literature and remarkably ATS Associated Cardiomyopathy (ATSAC) is emerging as a novel cardiovascular condition with its distinctive pathogenesis, risk factors, clinical features and prognosis. A comprehensive systematic review was performed to explore and analyze the current evidence on the association between ATS exposure and development of cardiomyopathy, biological mechanisms involved in pathogenesis of ATSAC, risk factors, clinical features and course of patients with ATSAC. Several animal studies, case reports, case series and case-control studies support the association between ATS exposure and ATSAC. Oxidative stress, accelerated apoptosis, increased p53 activity, cardiomyocyte necrosis, perfusion defects, fatty acid toxicity, altered gene expression, abnormal cardiac protein synthesis and function in addition to defects in intracellular calcium hemostasis present themselves as likely mechanisms of cardiotoxicity in ATSAC. Majority of patients with ATSAC were found to be male, young and presented late with severe dilated cardiomyopathy. Female ATS users predominantly develop Takotsubo type of ATSAC and in particular its atypical basal variant. Overall, cessation of ATS exposure seems to be associated with some degree of reversibility and recovery in ATSAC sufferers. PMID- 27663746 TI - Salami Publishing. PMID- 27663747 TI - Pathologic fracture of the distal humerus due to a textiloma. PMID- 27663748 TI - Transient motor paresis caused by herpes zoster. PMID- 27663749 TI - Open reduction and internal fixation of capitellar fracture through anterolateral approach with headless double- threaded compression screws: a series of 16 patients. PMID- 27663750 TI - Response to: Open reduction and internal fixation of capitellar fracture through anterolateral approach with headless double-threaded compression screws: a series of 16 patients. PMID- 27663751 TI - Associations Between Maltreatment History and Severity of Substance Use Behavior in Youth in Foster Care. AB - Substance use (SU) in youth remains a significant public health concern and a risk factor for morbidity and mortality in adolescents. The present study offers examination of the association between severity and chronicity of maltreatment history and SU in youth in foster care. Two hundred and ten (48% female) foster youth with a mean age of 12.71 years ( SD = 2.95 years) completed surveys using an audio-computer-assisted self-interview program. Results revealed 31% of participants reported past-year SU, and substance users had a mean CRAFFT score of 3.43 ( SD = 1.90). Reported age of SU onset was 11.08 years ( SD = 2.21 years). The SU measurement model demonstrated excellent fit in this sample. Accounting for both youth age and youth placement type, the structural model with maltreatment predicting SU severity demonstrated strong model fit with a significant path between maltreatment and SU. Youth in residential facilities and older youth had higher rates of use than those residing in traditional foster home environments and younger youth. Findings provide additional support for the link between maltreatment experiences and SU severity in foster youth and suggest the need for screening and intervention services appropriate for this high-risk population. PMID- 27663752 TI - Systematic engineering of TCA cycle for optimal production of a four-carbon platform chemical 4-hydroxybutyric acid in Escherichia coli. AB - To address climate change and environmental problems, it is becoming increasingly important to establish biorefineries for the production of chemicals from renewable non-food biomass. Here we report the development of Escherichia coli strains capable of overproducing a four-carbon platform chemical 4-hybroxybutyric acid (4-HB). Because 4-HB production is significantly affected by aeration level, genome-scale metabolic model-based engineering strategies were designed under aerobic and microaerobic conditions with emphasis on oxidative/reductive TCA branches and glyoxylate shunt. Several different metabolic engineering strategies were employed to develop strains suitable for fermentation both under aerobic and microaerobic conditions. It was found that microaerobic condition was more efficient than aerobic condition in achieving higher titer and productivity of 4 HB. The final engineered strain produced 103.4g/L of 4-HB by microaerobic fed batch fermentation using glycerol. The aeration-dependent optimization strategy of TCA cycle will be useful for developing microbial strains producing other reduced derivative chemicals of TCA cycle intermediates. PMID- 27663753 TI - Biotherapies in systemic lupus erythematosus: New targets. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over the past 15 years. The results of Phase II trials were encouraging but rarely borne out by Phase III trials. Recent data, which are discussed in detail in this review, allowed belimumab - a monoclonal antibody against BLyS (B lymphocyte stimulator) - to become the first biotherapy approved for use in SLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinical research into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. A new and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which the most promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor. In this review, we discuss study findings and their clinical relevance, present the most promising targets, and analyze possible explanations to negative results, such as inappropriate patient selection and treatment response criteria or the erratic use of high-dose glucocorticoid therapy. PMID- 27663754 TI - Infectious risk associated to orthopaedic surgery for rheumatoid arthritis patients treated by anti-TNFalpha. AB - INTRODUCTION: Although biotherapy has greatly improved the prognosis of RA many patients have still recourse to an orthopaedic surgery. The current recommendation for scheduled surgery is to discontinue administration of the biological agent two to six weeks before surgery. Reinitiating anti-TNF therapy is proposed when the patient has healed. We wanted to know whether patients treated with anti-TNFalpha were exposed to an infectious risk undergoing a surgical procedure and if discontinuation of anti-TNFalpha therapy altered the risk of surgical infection. METHODS: We conducted a systematic review of the literature in PubMed, Embase and Cochrane until March 2014. We selected studies that reported post-operative infections by comparing patients treated with anti TNFalpha to patients treated with csDMARD without biological treatment, or patients who continued anti-TNFalpha therapy to the patients who discontinued treatment prior to surgery. RESULTS: A first meta-analysis of 12 studies evaluating postoperative infection risk in patients treated with anti-TNFalpha showed that the postoperative infection risk doubled (RR=1.81 [1.31-2.50]). Seven studies were grouped into a second meta-analysis to evaluate the benefit of the preventive discontinuation of anti-TNFalpha. Discontinuation of treatment did not alter the post-operative infection risk significantly: RR=0.69 [0.39-1.21]. CONCLUSION: This study showed that patients treated with anti-TNFalpha were more at risk of post-operative infection undergoing orthopaedic surgery. Preventive discontinuation of anti-TNFalpha does not seem to change this risk. PMID- 27663757 TI - Multi-imaging modalities of intraosseous schwannoma of the scapula. PMID- 27663756 TI - RGTA(r)-based matrix therapy - A new branch of regenerative medicine in locomotion. AB - Matrix therapy is an innovative, minimally invasive approach in the field of regenerative medicine, that aims to promote tissue regeneration by reconstructing the cellular microenvironment following tissue injury. This approach has significant therapeutic potential in the treatment of pathologies characterized by tissue inflammation and damage, or following injury, conditions which can be incapacitating and cost-consuming. Heparan sulfate mimics, termed ReGeneraTing Agents (RGTA(r)s) have emerged as a unifying approach to treat these diverse pathologies. Today, skin and corneal healing topical products have already been used in clinics, demonstrating a proof of concept in humans. In this review, we present key evidence that RGTA(r)s regenerate damaged tissue in bone, muscle, tendon and nerve, with astonishing results. In animal models of bone surgical defects and inflammatory bone loss, RGTA(r) induced healing of injured bones by controlling inflammation and bone resorption, and stimulated bone formation by coordinating vascularization, recruitment and differentiation of competent cells from specific niches, restoring tissue quality to that of uninjured tissue, evoking true regeneration. In models of muscle injury, RGTA(r) had marked effects on healing speed and quality, evidenced by increased muscle fiber density, maturation, vascularization and reduced fibrosis, more mature motor endplates and functional recovery. Applications merging RGTA(r)-based matrix therapy and cell therapy, combining Extra-Cellular Matrix reconstruction with cells required for optimal tissue repair show significant promise. Hence restoration of the proper microenvironment is a new paradigm in regenerative medicine. Harnessing the potential of RGTA(r) in this brave, new vision of regenerative therapy will therefore be the focus of future studies. PMID- 27663758 TI - Nontraumatic tumoral calcinosis. PMID- 27663755 TI - Pro-inflammatory and anti-inflammatory T cells in giant cell arteritis. AB - Giant cell arteritis is an autoimmune disease defined by explicit tissue tropism to the walls of medium and large arteries. Pathognomic inflammatory lesions are granulomatous in nature, emphasizing the functional role of CD4T cells and macrophages. Evidence for a pathogenic role of antibodies and immune complexes is missing. Analysis of T cell populations in giant cell arteritis, both in the tissue lesions and in the circulation, has supported a model of broad, polyclonal T cell activation, involving an array of functional T cell lineages. The signature of T cell cytokines produced by vasculitic lesions is typically multifunctional, including IL-2, IFN-gamma, IL-17, IL-21, and GM-CSF, supportive for a general defect in T cell regulation. Recent data describing the lack of a lymph node-based population of anti-inflammatory T cells in giant cell arteritis patients offers a fresh look at the immunopathology of this vasculitis. Due to defective CD8+NOX2+ regulatory T cells, giant cell arteritis patients appear unable to curtail clonal expansion within the CD4T cell compartment, resulting in widespread CD4T cell hyperimmunity. Why unopposed expansion of committed CD4 effector T cells would lead to invasion of the walls of medium and large arteries needs to be explored in further investigations. PMID- 27663759 TI - High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study. AB - INTRODUCTION: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. PATIENTS AND METHODS: We conducted a multicenter phase 1 study that combined HSRT (3 * 9 Gy) and zoledronate in patients with vertebral metastasis (NCT01219790). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. RESULTS: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). CONCLUSION: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects. PMID- 27663760 TI - Multinational Prospective Study of Patient-Reported Outcomes After Prostate Radiation Therapy: Detailed Assessment of Rectal Bleeding. AB - PURPOSE: The new short Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) patient-reported health-related quality of life (HRQOL) tool has removed the rectal bleeding question from the previous much longer version, EPIC-26. Herein, we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospective multicenter cohorts. METHODS AND MATERIALS: In a prospective multicenter test cohort (n=865), EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011. A second prospective multicenter cohort (n=442) was used for independent validation. A repeated-effects model was used to predict the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores. RESULTS: Two years after radiation therapy, 91% of patients were free of bleeding, and only 2.6% reported bothersome bleeding problems. Correlations between EPIC-26 and EPIC-CP bowel scores were very high (r2=0.90-0.96) and were statistically improved with the addition of rectal bleeding information (r2=0.94-0.98). Considering all patients, only 0.2% of patients in the test cohort and 0.7% in the validation cohort reported bothersome bleeding and had clinically relevant HRQOL changes missed with EPIC-CP. However, of the 2.6% (n=17) of men with bothersome rectal bleeding in the test cohort, EPIC-CP failed to capture 1 patient (6%) as experiencing meaningful declines in bowel HRQOL. CONCLUSIONS: Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding, and <1% of patients experience bothersome bleeding and are not captured by EPIC-CP as having meaningful HRQOL declines after radiation therapy. However, in the small subset of patients with bothersome rectal bleeding, the longer EPIC-26 should strongly be considered, given its superior performance in this patient subset. PMID- 27663761 TI - Contemporary Trends in Radiation Oncology Resident Research. AB - PURPOSE: To test the hypothesis that recent resident research productivity might be different than a decade ago, and to provide contemporary information about resident scholarly activity. METHODS AND MATERIALS: We compiled a list of radiation oncology residents from the 2 most recent graduating classes (June 2014 and 2015) using the Association of Residents in Radiation Oncology annual directories. We queried the PubMed database for each resident's first-authored publications from postgraduate years (PGY) 2 through 5, plus a 3-month period after residency completion. We abstracted corresponding historical data for 2002 to 2007 from the benchmark publication by Morgan and colleagues (Int J Radiat Oncol Biol Phys 2009;74:1567-1572). We tested the null hypothesis that these 2 samples had the same distribution for number of publications using the Wilcoxon rank-sum test. We explored the association of demographic factors and publication number using multivariable zero-inflated Poisson regression. RESULTS: There were 334 residents publishing 659 eligible first-author publications during residency (range 0-17; interquartile range 0-3; mean 2.0; median 1). The contemporary and historical distributions were significantly different (P<.001); contemporary publication rates were higher. Publications accrued late in residency (27% in PGY 4, 59% in PGY-5), and most were original research (75%). In the historical cohort, half of all articles were published in 3 journals; in contrast, the top half of contemporary publications were spread over 10 journals-most commonly International Journal of Radiation Oncology * Biology * Physics (17%), Practical Radiation Oncology (7%), and Radiation Oncology (4%). Male gender, non-PhD status, and larger residency size were associated with higher number of publications in the multivariable analysis. CONCLUSION: We observed an increase in first-author publications during training compared with historical data from the mid-2000s. These contemporary figures may be useful to medical students considering radiation oncology, current residents, training programs, and prospective employers. PMID- 27663763 TI - Priors in perception: Top-down modulation, Bayesian perceptual learning rate, and prediction error minimization. AB - I discuss top-down modulation of perception in terms of a variable Bayesian learning rate, revealing a wide range of prior hierarchical expectations that can modulate perception. I then switch to the prediction error minimization framework and seek to conceive cognitive penetration specifically as prediction error minimization deviations from a variable Bayesian learning rate. This approach retains cognitive penetration as a category somewhat distinct from other top-down effects, and carves a reasonable route between penetrability and impenetrability. It prevents rampant, relativistic cognitive penetration of perception and yet is consistent with the continuity of cognition and perception. PMID- 27663762 TI - Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation Induced Pulmonary Fibrosis in a Murine Model. AB - PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. METHODS AND MATERIALS: C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for beta-galactosidase activity. RESULTS: Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 +/- 11.8 MUg per lung; irradiation plus rapamycin, 21.4 +/- 6.0 MUg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1beta and transforming growth factor beta induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). CONCLUSIONS: Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes. PMID- 27663764 TI - The countermovement jump to monitor neuromuscular status: A meta-analysis. AB - OBJECTIVES: The primary objective of this meta-analysis was to compare countermovement jump (CMJ) performance in studies that reported the highest value as opposed to average value for the purposes of monitoring neuromuscular status (i.e., fatigue and supercompensation). The secondary aim was to determine the sensitivity of the dependent variables. DESIGN: Systematic review with meta analysis. METHODS: The meta-analysis was conducted on the highest or average of a number of CMJ variables. Multiple literature searches were undertaken in Pubmed, Scopus, and Web of Science to identify articles utilizing CMJ to monitor training status. Effect sizes (ES) with 95% confidence interval (95% CI) were calculated using the mean and standard deviation of the pre- and post-testing data. The coefficient of variation (CV) with 95% CI was also calculated to assess the level of instability of each variable. Heterogeneity was assessed using a random effects model. RESULTS: 151 articles were included providing a total of 531 ESs for the meta-analyses; 85.4% of articles used highest CMJ height, 13.2% used average and 1.3% used both when reporting changes in CMJ performance. Based on the meta-analysis, average CMJ height was more sensitive than highest CMJ height in detecting CMJ fatigue and supercompensation. Furthermore, other CMJ variables such as peak power, mean power, peak velocity, peak force, mean impulse, and power were sensitive in tracking the supercompensation effects of training. CONCLUSIONS: The average CMJ height was more sensitive than highest CMJ height in monitoring neuromuscular status; however, further investigation is needed to determine the sensitivity of other CMJ performance variables. PMID- 27663765 TI - Potentially missed acute pericarditis: atypical pericarditis. PMID- 27663766 TI - ED triage pain protocol reduces time to receiving analgesics in patients with painful conditions. AB - BACKGROUND: Studies suggest that collaborative nursing protocols initiated in triage improve emergency department (ED) throughput and decrease time to treatment. OBJECTIVE: The objective of the study is to determine if an ED triage pain protocol improves time to provision of analgesics. METHODS: Retrospective data abstracted via electronic medical record of patients at a safety net facility with 67 000 annual adult visits. Patients older than 18 years who presented to the ED between March 1, 2011, and May 31, 2013, with 1 of 6 conditions were included: back pain, dental pain, extremity trauma, sore throat, ear pain, or pain from an abscess. A 3-month orientation to an ED nurse-initiated pain protocol began on March 1, 2012. Nurses administered oral analgesics per protocol, beginning with acetaminophen or ibuprofen and progressing to oxycodone. Preimplementation and postimplementation analyses examined differences in time to analgesics. Multivariable analysis modeled time to analgesics as a function of patient factors. RESULTS: Over a 27-month period, 23 409 patients were included: 13 112 received pain medications and 10 297 did not. A total of 12 240 (52%) were male, 12 578 (54%) were African American, and 7953 (34%) were white, with a mean (SD) age of 39 years (13 years). The pain protocol was used in 1002 patients. There was a significant change in mean time (minutes) to provision of analgesics between preimplementation (238) and postimplementation (168) (P < .0001). Linear regression showed the protocol-delivered medications to younger patients and of lower acuity in a reduced time. Variables not related to time to provision of medication included sex, payer, and race. CONCLUSION: Emergency department triage pain protocol decreased time to provision of pain medications and did so without respect to payer category, sex, or race. PMID- 27663767 TI - Microstructure and mechanics of human resistance arteries. AB - Vascular diseases such as diabetes and hypertension cause changes to the vasculature that can lead to vessel stiffening and the loss of vasoactivity. The microstructural bases of these changes are not presently fully understood. We present a new methodology for stain-free visualization, at a microscopic scale, of the morphology of the main passive components of the walls of unfixed resistance arteries and their response to changes in transmural pressure. Human resistance arteries were dissected from subcutaneous fat biopsies, mounted on a perfusion myograph, and imaged at varying transmural pressures using a multimodal nonlinear microscope. High-resolution three-dimensional images of elastic fibers, collagen, and cell nuclei were constructed. The honeycomb structure of the elastic fibers comprising the internal elastic layer became visible at a transmural pressure of 30 mmHg. The adventitia, comprising wavy collagen fibers punctuated by straight elastic fibers, thinned under pressure as the collagen network straightened and pulled taut. Quantitative measurements of fiber orientation were made as a function of pressure. A multilayer analytical model was used to calculate the stiffness and stress in each layer. The adventitia was calculated to be up to 10 times as stiff as the media and experienced up to 8 times the stress, depending on lumen diameter. This work reveals that pressure induced reorganization of fibrous proteins gives rise to very high local strain fields and highlights the unique mechanical roles of both fibrous networks. It thereby provides a basis for understanding the micromechanical significance of structural changes that occur with age and disease. PMID- 27663768 TI - The chromatin-binding protein Smyd1 restricts adult mammalian heart growth. AB - All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. PMID- 27663769 TI - Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans. AB - There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ~25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts. PMID- 27663770 TI - Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina. AB - Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (n = 71) and healthy subjects as control (n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 +/- 0.142 vs. 0.086 +/- 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 +/- 0.107 vs. 0.106 +/- 0.149 mg/dl, P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 +/- 1.64 vs. 14.2 +/- 5.39 ng/ml, P = 0.019 (11,12-DHET); 15.2 +/- 4.39 vs. 17.9 +/- 4.73 ng/ml, P = 0.025 (14,15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction. PMID- 27663773 TI - Evolution of Cilia. AB - Anton van Leeuwenhoek's startling microscopic observations in the 1600s first stimulated fascination with the way that cells use cilia to generate currents and to swim in a fluid environment. Research in recent decades has yielded deep knowledge about the mechanical and biochemical nature of these organelles but only opened a greater fascination about how such beautifully intricate and multifunctional structures arose during evolution. Answers to this evolutionary puzzle are not only sought to satisfy basic curiosity, but also, as stated so eloquently by Dobzhansky (Am Zool 4: 443 [1964]), because "nothing in biology makes sense except in the light of evolution." Here I attempt to summarize current knowledge of what ciliary organelles of the last eukaryotic common ancestor (LECA) were like, explore the ways in which cilia have evolved since that time, and speculate on the selective processes that might have generated these organelles during early eukaryotic evolution. PMID- 27663771 TI - Oh, the places you'll go! My many colored serotonin (apologies to Dr. Seuss). AB - Serotonin [5-hydroxytryptamine (5-HT)] has a truly fascinating history in the cardiovascular world. Discovered in the blood, 5-HT has long been appropriately regarded as a vasoconstrictor. A multitude of in vitro studies of isolated vessels support that addition of 5-HT causes vascular contraction. In only a few cases was 5-HT a vasodilator. Moreover, the potency and threshold of 5-HT causing contraction is increased in arteries from hypertensive vs. normotensive subjects, both animal and human. As such, we and others have hypothesized that 5-HT would contribute to hypertension by elevating arterial tone. In stark contrast to these decades of findings, we observed that a chronic infusion of 5-HT into conscious rats caused a reduction in blood pressure and nearly normalized blood pressure of experimentally hypertensive rats. Going back to the early work of Irvine Page, one of the scientists who discovered 5-HT, reveals an early recognized but never understood ability of 5-HT to reduce systemic blood pressure. Our laboratory, in collaboration with colleagues around the world, has dedicated itself to understanding the mechanisms of 5-HT-induced reduction in blood pressure. This manuscript takes you through a brief history of the discovery of 5-HT, in vitro serotonergic pharmacology of blood vessels, in vivo work with 5-HT and our studies that suggests the venous vasculature, potentially in combination with small arterioles, may be important to the actions of 5-HT in reducing blood pressure. 5-HT has certainly ended up in a place I never expected it to go. PMID- 27663772 TI - The Plant Circadian Clock: From a Simple Timekeeper to a Complex Developmental Manager. AB - The plant circadian clock allows organisms to anticipate the predictable changes in the environment by adjusting their developmental and physiological traits. In the last few years, it was determined that responses known to be regulated by the oscillator are also able to modulate clock performance. These feedback loops and their multilayer communications create a complex web, and confer on the clock network a role that exceeds the measurement of time. In this article, we discuss the current knowledge of the wiring of the clock, including the interplay with metabolism, hormone, and stress pathways in the model species Arabidopsis thaliana We outline the importance of this system in crop agricultural traits, highlighting the identification of natural alleles that alter the pace of the timekeeper. We report evidence supporting the understanding of the circadian clock as a master regulator of plant life, and we hypothesize on its relevant role in the adaptability to the environment and the impact on the fitness of most organisms. PMID- 27663775 TI - Sudden sensorineural hearing loss due to an osteolytic lesion. PMID- 27663774 TI - Alternative Watson-Crick Synthetic Genetic Systems. AB - In its "grand challenge" format in chemistry, "synthesis" as an activity sets out a goal that is substantially beyond current theoretical and technological capabilities. In pursuit of this goal, scientists are forced across uncharted territory, where they must answer unscripted questions and solve unscripted problems, creating new theories and new technologies in ways that would not be created by hypothesis-directed research. Thus, synthesis drives discovery and paradigm changes in ways that analysis cannot. Described here are the products that have arisen so far through the pursuit of one grand challenge in synthetic biology: Recreate the genetics, catalysis, evolution, and adaptation that we value in life, but using genetic and catalytic biopolymers different from those that have been delivered to us by natural history on Earth. The outcomes in technology include new diagnostic tools that have helped personalize the care of hundreds of thousands of patients worldwide. In science, the effort has generated a fundamentally different view of DNA, RNA, and how they work. PMID- 27663776 TI - [Severe pulmonary hypertension secondary to hyperthyroidism]. PMID- 27663777 TI - The assessment of status of tobacco smoking among urban primary schoolchildren in Madagascar. AB - The prevalence of tobacco smoking among adolescents aged 13-15 years old in Madagascar was previously reported to be higher than the average in other African regions. A preventive approach is urgently needed to avoid the initiation of early tobacco smoking. Therefore, the aims of this study were to evaluate the status of tobacco smoking among primary schoolchildren in Madagascar and explore the factors associated with initiation of tobacco smoking in the young. This study was conducted in the Mahajanga region of Madagascar. Three primary schools in this region and children of both genders between the ages of nine to 12 years old were randomly selected and approached to participate in this study. A self administered questionnaire modified from the Global Youth Tobacco Survey Core Questionnaire 2007 was used to assess the status of tobacco smoking among primary schoolchildren. A total of 150 schoolchildren (14.0%) declared that they had smoked tobacco, with 30% starting to smoke tobacco at the age of seven or younger. The prevalence of tobacco smoking was lower among schoolchildren with non-smoking parents (p < 0.001) or non-smoking close friends (p < 0.001). Furthermore, schoolchildren's antismoking intention (p < 0.001) and their knowledge about the harmfulness of tobacco (p = 0.009) had significant effects on the prevalence of tobacco smoking. The results of this study indicate that tobacco smoking among schoolchildren in Madagascar may be influenced by peers, or parents, as well as smoking intention and knowledge about the harmfulness of tobacco use. PMID- 27663778 TI - Biological Identity of Nanoparticles In Vivo: Clinical Implications of the Protein Corona. AB - Despite the advances in biomedical applications of nanoparticle (NP) and numerous publications, few NPs have made it to clinical trials and even fewer have reached clinical practice. This wide gap between bench discoveries and clinical applications is mainly because of our limited understanding of the biological identity of NPs. In physiological environments, NPs are coated by a 'protein corona' (PC), critically affecting physiological and therapeutic responses. To date, nearly all studies attempting to characterize the PC have been conducted in vitro. Here, we review recent advances in our understanding of the in vivo PC. We also discuss recent developments of quantitative models to predict biological interactions and how they offer new opportunities for the clinical translation of NPs. PMID- 27663779 TI - The role of middle managers in tobacco control after a national smoke-free hospital campus ban. AB - BACKGROUND: Much of the recent health services research on tobacco control implementation has explored general views and perceptions of health professionals and has rarely taken into account middle management's perspectives. We state that middle managers may facilitate the implementation of smoke-free campus bans and thereby improve their effectiveness. The aim of this study was to assess middle managers' behaviors to enforce a new national smoke-free hospital campus ban, to evaluate their perceptions of the level of compliance of the new regulation, and to explore their attitudes towards how smoking affects the work environment. METHODS: We used a cross-sectional survey, conducted online to evaluate middle managers of a general hospital in Catalonia, Spain. Close-ended and open-ended questions were included. Results were analyzed by using quantitative and qualitative methods. The managers' open opinions to the proposed topics were assessed using UCINET, and a graph was generated in NetDraw. RESULTS: Sixty-three of the invited managers (78.7 %) participated in the survey. 87.2 % of them agreed that the hospital complied with the smoke-free campus ban and 79.0 % agreed that managers have an important role in enforcing the ban. They also perceived that smoking disturbs the dynamics of work, is a cause of conflict between smokers and non-smokers, and harms both the professional and the organization images. However, 96.8 % of respondents have never given out fines or similar measures and their active role in reminding others of the policy was limited; in addition, 68.2 % considered that hospitals should provide tobacco cessation treatments. Smoker middle managers were more likely than non-smokers to perceive that smoking has little impact on work. CONCLUSIONS: Middle managers play a limited role in controlling tobacco consumption; smokers are less prone to think that smoking disturbs work dynamics than non-smokers. Tailored training and clear proceedings for middle managers could encourage more active roles. PMID- 27663780 TI - Predicting spatial dynamics of infectious disease: Causes and consequences: Comment on "Pattern transitions in spatial epidemics: Mechanisms and emergent properties" by Gui-Quan Sun et al. PMID- 27663781 TI - Current and Former Smokers' Use of Electronic Cigarettes for Quitting Smoking: An Exploratory Study of Adolescents and Young Adults. AB - Background: This exploratory study examines the prevalence and predictors of current and former smokers' use of electronic (e-) cigarettes for smoking cessation among a sample of adolescent and young adult established smokers. Methods: We conducted school-wide surveys in two middle (n = 1166) and four high schools (n = 3614) in fall 2013 and one public college (n = 625) in spring 2014. We analyzed data from 189 established smokers (reported smoking 100 cigarettes in their lifetime) who also reported ever-use of e-cigarettes (50.7% female, 89.4% White race, Mage 18.3 [SD = 2.8]). We further classified participants as current smokers (reported past-month cigarette smoking) and former smokers (no past-month smoking). Adjusted logistic regression assessed associations of using e cigarettes to quit smoking with demographic, cigarette and e-cigarette use patterns, e-cigarette flavor preference, and risk perception variables. Results: Overall, 41.8% of the sample reported that they "have used an e-cigarette to quit smoking." In adjusted models, older age, White race, higher e-cigarette frequency, and preference for using a combination of e-cigarette flavors predicted increased odds of having used e-cigarettes to quit smoking (p < .05). Using e-cigarettes to quit smoking was not associated with current or former cigarette smoking status or perceptions that "e-cigarettes help people quit smoking" or "e-cigarettes are safer than quit smoking medications." Conclusions: Adolescents and young adults who report more frequent e-cigarette use and preference for using flavor combinations are more likely to use e-cigarettes for smoking cessation. Future studies are needed to determine whether e-cigarette use leads to tobacco abstinence in youth smokers. Implications: Among young established smokers, more frequent e-cigarette use and preference for using flavors mixed together, but not perceptions of harmfulness of e-cigarettes or comparative safety of e-cigarettes compared with cigarettes or other smoking cessation medications or helpfulness of e-cigarettes in quitting smoking, are associated with using e-cigarettes for smoking cessation. PMID- 27663782 TI - Using Experimental Auctions to Examine Demand for E-Cigarettes. AB - Background: E-cigarettes are the latest in a line of potentially reduced exposure products that have garnered interest among smokers. Methods: In this paper, we use experimental auctions to estimate smokers' demand for e-cigarettes and to assess the impact of advertisements on willingness to pay. These are actual auctions, with winners and losers, which means hypothetical biases often seen in surveys are minimized. Results: We find smokers have positive demand for e cigarettes, and that the print advertisements used in our study had greater effectiveness than video ads (b = 2.00, p < .05) in terms of increasing demand for disposable e-cigarettes. Demand was greater for reusable versus disposable e cigarettes. In multivariate models, demand for e-cigarettes was higher among non white participants and among smokers willing to pay more for cigarettes. Conclusions: Our findings suggest that cigarette smokers are interested in e cigarettes as alternatives to traditional products, particularly for reusable forms, and that this demand can be influenced by messaging/advertising. Implications: Given these reduced harm products are appealing, if smokers are able to switch completely to e-cigarettes, there is a good chance for accrual of significant harm reduction. PMID- 27663783 TI - A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May be Differentially Associated With Cigarettes per Day and Tobacco-Related Problems. AB - Introduction: Tobacco use is associated with variation at the 15q25 gene cluster and the cytochrome P450 (CYP) genes CYP2A6 and CYP2B6. Despite the variety of outcomes associated with these genes, few studies have adopted a data-driven approach to defining tobacco use phenotypes for genetic association analyses. We used factor analysis to generate a tobacco use measure, explored its incremental validity over a simple indicator of tobacco involvement: cigarettes per day (CPD), and tested both phenotypes in a genetic association study. Methods: Data were from the University of California, San Francisco Family Alcoholism Study (n = 1942) and a Native American sample (n = 255). Factor analyses employed a broad array of tobacco use variables to establish the candidate phenotype. Subsequently, we conducted tests for association with variants in the nicotinic acetylcholine receptor and CYP genes. We explored associations with CPD and our measure. We then examined whether the variants most strongly associated with our measure remained associated after controlling for CPD. Results: Analyses identified one factor that captured tobacco-related problems. Variants at 15q25 were significantly associated with CPD after multiple testing correction (rs938682: p = .00002, rs1051730: p = .0003, rs16969968: p = .0003). No significant associations were obtained with the tobacco use phenotype; however, suggestive associations were observed for variants in CYP2B6 near CYP2A6 (rs45482602: ps = .0082, .0075) and CYP4Z2P (rs10749865: ps = .0098, .0079). Conclusions: CPD captures variation at 15q25. Although strong conclusions cannot be drawn, these finding suggest measuring additional dimensions of problems may detect genetic variation not accounted for by smoking quantity. Replication in independent samples will help further refine phenotype definition efforts. Implications: Different facets of tobacco-related problems may index unique genetic risk. CPD, a simple measure of tobacco consumption, is associated with variants at the 15q25 gene cluster. Additional dimensions of tobacco problems may help to capture variation at 19q13. Results demonstrate the utility of adopting a data-driven approach to defining phenotypes for genetic association studies of tobacco involvement and provide results that can inform replication efforts. PMID- 27663784 TI - Causes and consequences of delays in treatment-withdrawal from PVS patients: a case study of Cumbria NHS Clinical Commissioning Group v Miss S and Ors [2016] EWCOP 32. AB - Life-extending treatment, in the form of artificial nutrition and hydration, is often provided to people in permanent vegetative states (PVS) in England and Wales for many years, even when their family believes the patient would not want it and despite the fact that no court in the UK has ever found in favour of continuing such treatment for a patient with a confirmed PVS diagnosis. The first half of this article presents a close analysis of the recent case of Cumbria NHS Clinical Commissioning Group v Miss S and Ors [2016] EWCOP 32. It examines the causes of delay in bringing this case to court and reaching a final judgment. It draws not only on the published judgment, but also on the two authors' involvement in supporting the family (before, during and subsequent to the court hearings) as a result of their academic and policy-related work in this area. This includes conversations with the family and with members of the clinical and legal teams, and observations in court. The second part of the article draws out the ethical and practical implications of the findings for theory and policy and suggests ways forward in relation to (a) the provision and inspection of care for these patients; (b) legal practice in relation to 'best interests' and (c) the perceived requirement under English law for a court application before life prolonging treatment can be withdrawn from PVS patients-even in the absence of any 'in principle' opposition. PMID- 27663786 TI - A model for sea lice (Lepeophtheirus salmonis) dynamics in a seasonally changing environment. AB - Sea lice (Lepeophtheirus salmonis) are a significant source of monetary losses on salmon farms. Sea lice exhibit temperature-dependent development rates and salinity-dependent mortality, but to date no deterministic models have incorporated these seasonally varying factors. To understand how environmental variation and life history characteristics affect sea lice abundance, we derive a delay differential equation model and parameterize the model with environmental data from British Columbia and southern Newfoundland. We calculate the lifetime reproductive output for female sea lice maturing to adulthood at different times of the year and find differences in the timing of peak reproduction between the two regions. Using a sensitivity analysis, we find that sea lice abundance is more sensitive to variation in mean annual water temperature and mean annual salinity than to variation in life history parameters. Our results suggest that effective sea lice management requires consideration of site-specific temperature and salinity patterns and, in particular, that the optimal timing of production cycles and sea lice treatments might vary between regions. PMID- 27663787 TI - Information content of household-stratified epidemics. AB - Household structure is a key driver of many infectious diseases, as well as a natural target for interventions such as vaccination programs. Many theoretical and conceptual advances on household-stratified epidemic models are relatively recent, but have successfully managed to increase the applicability of such models to practical problems. To be of maximum realism and hence benefit, they require parameterisation from epidemiological data, and while household stratified final size data has been the traditional source, increasingly time series infection data from households are becoming available. This paper is concerned with the design of studies aimed at collecting time-series epidemic data in order to maximize the amount of information available to calibrate household models. A design decision involves a trade-off between the number of households to enrol and the sampling frequency. Two commonly used epidemiological study designs are considered: cross-sectional, where different households are sampled at every time point, and cohort, where the same households are followed over the course of the study period. The search for an optimal design uses Bayesian computationally intensive methods to explore the joint parameter-design space combined with the Shannon entropy of the posteriors to estimate the amount of information in each design. For the cross-sectional design, the amount of information increases with the sampling intensity, i.e., the designs with the highest number of time points have the most information. On the other hand, the cohort design often exhibits a trade-off between the number of households sampled and the intensity of follow-up. Our results broadly support the choices made in existing epidemiological data collection studies. Prospective problem-specific use of our computational methods can bring significant benefits in guiding future study designs. PMID- 27663785 TI - Using age-stratified incidence data to examine the transmission consequences of pertussis vaccination. AB - Pertussis is a highly infectious respiratory disease that has been on the rise in many countries worldwide over the past several years. The drivers of this increase in pertussis incidence remain hotly debated, with a central and long standing hypothesis that questions the ability of vaccines to eliminate pertussis transmission rather than simply modulate the severity of disease. In this paper, we present age-structured case notification data from all provinces of Thailand between 1981 and 2014, a period during which vaccine uptake rose substantially, permitting an evaluation of the transmission impacts of vaccination. Our analyses demonstrate decreases in incidence across all ages with increased vaccine uptake an observation that is at odds with pertussis case notification data in a number of other countries. To explore whether these observations are consistent with a rise in herd immunity and a reduction in bacterial transmission, we analyze an age-structured model that incorporates contrasting hypotheses concerning the immunological and transmission consequences of vaccines. Our results lead us to conclude that the most parsimonious explanation for the combined reduction in incidence and the shift to older age groups in the Thailand data is vaccine induced herd immunity. PMID- 27663788 TI - Estimates of the risk of large or long-lasting outbreaks of Middle East respiratory syndrome after importations outside the Arabian Peninsula. AB - We quantify outbreak risk after importations of Middle East respiratory syndrome outside the Arabian Peninsula. Data from 31 importation events show strong statistical support for lower transmissibility after early transmission generations. Our model projects the risk of >=10, 100, and 500 transmissions as 11%, 2%, and 0.02%, and >=1, 2, 3, and 4 generations as 23%, 14%, 0.9%, and 0.05%, respectively. Our results suggest tempered risk of large, long-lasting outbreaks with appropriate control measures. PMID- 27663789 TI - Linking the seroresponse to infection to within-host heterogeneity in antibody production. AB - A recently published model for the serum antibody response to infection appeared well suited for use in statistical analyses of longitudinal serological data. The published model assumed exponential decay with fixed rates for pathogen and serum antibody kinetics, ignoring any within-host heterogeneity in the seroresponse. A bi-exponential model shows that there is rapid initial decay followed by a prolonged period of persistent low serum antibody concentrations. We propose a small modification of the decay model that greatly increases its flexibility by allowing for non-exponential antibody decay. The modified model produces power functions that may be interpreted as a mixture of exponential decay curves, with a mixing distribution representing the relative contribution of many centres of antibody production to the serum antibody concentration. Fitting the power function decay model to observed longitudinal data for pertussis shows improved goodness of fit compared to the exponential decay model, with estimates for the shape parameter (r=2.2; 95% CI (1.7-2.8)) that differ from exponential shape (r=1). The power function decay model predicts more persistent antibody concentrations in the long term (symptomatic threshold reached >30 years after infection) which, when used in biomarker studies, will lead to lower estimates of seroconversion rates compared to exponential antibody decay. PMID- 27663790 TI - Dengue serotype immune-interactions and their consequences for vaccine impact predictions. AB - Dengue is one of the most important and wide-spread viral infections affecting human populations. The last few decades have seen a dramatic increase in the global burden of dengue, with the virus now being endemic or near-endemic in over 100 countries world-wide. A recombinant tetravalent vaccine candidate (CYD-TDV) has recently completed Phase III clinical efficacy trials in South East Asia and Latin America and has been licensed for use in several countries. The trial results showed moderate-to-high efficacies in protection against clinical symptoms and hospitalisation but with so far unknown effects on transmission and infections per se. Model-based predictions about the vaccine's short- or long term impact on the burden of dengue are therefore subject to a considerable degree of uncertainty. Furthermore, different immune interactions between dengue's serotypes have frequently been evoked by modelling studies to underlie dengue's oscillatory dynamics in disease incidence and serotype prevalence. Here we show how model assumptions regarding immune interactions in the form of antibody-dependent enhancement, temporary cross-immunity and the number of infections required to develop full immunity can significantly affect the predicted outcome of a dengue vaccination campaign. Our results thus re-emphasise the important gap in our current knowledge concerning the effects of previous exposure on subsequent dengue infections and further suggest that intervention impact studies should be critically evaluated by their underlying assumptions about serotype immune-interactions. PMID- 27663791 TI - Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by alpha-linolenic acid supplementation in mice. AB - BACKGROUND: Adequate consumption of polyunsaturated fatty acids (PUFA) is vital for normal development and functioning of the central nervous system. The long chain n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid are anti inflammatory and neuroprotective in the models of central nervous system injury including traumatic brain injury (TBI). In the present study, we tested whether a higher brain DHA status in a mouse model on an adequate dietary alpha-linolenic acid (ALA) leads to reduced neuroinflammation and improved spontaneous recovery after TBI in comparison to a moderately lowered brain DHA status that can occur in humans. METHODS: Mice reared on diets with differing ALA content were injured by a single cortical contusion impact. Change in the expression of inflammatory cytokines was measured, and cellular changes occurring after injury were analyzed by immunostaining for macrophage/microglia and astrocytes. Behavioral studies included rotarod and beam walk tests and contextual fear conditioning. RESULTS: Marginal supply (0.04 %) of ALA as the sole dietary source of n-3 PUFA from early gestation produced reduction of brain DHA by 35 % in adult offspring mice in comparison to the mice on adequate ALA diet (3.1 %). The DHA-depleted group showed significantly increased TBI-induced expression of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 in the brain as well as slower functional recovery from motor deficits compared to the adequate ALA group. Despite the reduction of pro-inflammatory cytokine expression, adequate ALA diet did not significantly alter either microglia/macrophage density around the contusion site or the relative M1/M2 phenotype. However, the glial fibrillary acidic protein immunoreactivity was reduced in the injured cerebral cortex of the mice on adequate ALA diet, indicating that astrocyte activation may have contributed to the observed differences in cellular and behavioral responses to TBI. CONCLUSIONS: Increasing the brain DHA level even from a moderately DHA-depleted state can reduce neuroinflammation and improve functional recovery after TBI, suggesting possible improvement of functional outcome by increasing dietary n-3 PUFA in human TBI. PMID- 27663792 TI - Suture Annuloplasty Significantly Improves the Durability of Bicuspid Aortic Valve Repair. AB - BACKGROUND: Isolated repair of the regurgitant bicuspid aortic valve (BAV) has yielded suboptimal durability, with annular dilatation being important risk factor for recurrent aortic regurgitation. We hypothesized that adding a suture annuloplasty (SA) should lead to improved repair stability. METHODS: Between July 1999 and September 2014, 268 patients (mean age, 41 +/- 13 years, 249 male) underwent isolated BAV repair. From January 2009 to September 2014, 164 consecutive patients (study group) underwent SA using either braided polyester (n = 37) or expanded polytetrafluorethylene (PTFE) (n = 127). Patients who underwent surgery prior to January 2009 served as controls (n = 104). All patients were followed (98.9% complete, 1 week to 181 months). RESULTS: Annular size was larger in the study group (p < 0.001) and age was lower (p < 0.001). There were no differences between the groups regarding other clinical data. Hospital mortality was 0.7% (n = 2), 10-year survival was 94.2%. Thirty-six patients required valve related reoperations (8 days to 94 months postoperatively; controls = 32, study = 4). Complications related to SA (ventricular septal defect, interference with coronary artery) occurred in 6 (3.7%) patients, in 4 (10.8%) patients with polyester SA and in 2 (1.6%) patients with PTFE. In the control group freedom from reoperation at 5 and 10 years was 73.2% and 63.7%, respectively. With SA, 5 year stability was significantly improved to 92.6% (p = 0.0006); it was 96.7% for PTFE versus 83.5% for polyester SA (p = 0.0132). CONCLUSIONS: Annular dilatation is a risk factor for failure after repair of regurgitant BAV. Its elimination through the use of SA significantly improves repair stability. With PTFE as material for SA optimal repair stability and minimal local complications are achieved. PMID- 27663793 TI - Cavity Wall Thickness in Solitary Cavitary Lung Adenocarcinomas Is a Prognostic Indicator. AB - BACKGROUND: Although cavitary lung cancers typically show thick-walled cavities on radiology, thin-walled cancers have recently been reported. However, the prognostic and pathologic differences between thin-walled and thick-walled variants are unclear. We reviewed detailed histologic features and survival outcomes of cavitary pulmonary adenocarcinomas to assess pathologic attributes, focusing particularly on cavity wall thickness. METHODS: We studied 132 patients diagnosed with lung adenocarcinoma involving cavitary formation, as determined with high-resolution computed tomography or histology, between 1998 and 2007. Using receiver-operating characteristics curve analysis, we established a cutoff value for cavity wall thickness based on disease-specific survival. Cavitary adenocarcinomas were grouped into thick-walled or thin-walled types according to this cutoff, as measured by computed tomography. RESULTS: The thick-walled group comprised lung adenocarcinoma patients with a cavity wall thickness of greater than 4 mm (n = 65); the thin-walled group comprised patients with a cavity wall thickness of 4 mm or less (n = 67). The thick-walled group had a higher frequency of solid predominant tumors (p < 0.01), vascular invasion (p < 0.001), lymphatic invasion (p < 0.01), necrosis (p < 0.001), obstructive pneumonia (p < 0.01), intracavity abscess (p < 0.01), and bronchiolar obstruction (p = 0.02). Lepidic predominant (p = 0.09) and papillary predominant patterns (p = 0.08) were more common in the thin-walled group. Multivariate analysis revealed cavity wall thickness to be an independent prognostic factor (p = 0.022). CONCLUSIONS: The pathologic and prognostic implications of thick-walled cavities versus thin walled cavities in lung carcinoma patients, defined according to our cutoff, were found to be distinct. PMID- 27663794 TI - The interaction effects of risk factors for hypertension in adults: a cross sectional survey in Guilin, China. AB - BACKGROUND: The prevalence of hypertension in adults is increasing each year and has become a main public health issue worldwide. We must consider the impact of both individual factors and interactions among these factors on hypertension in adults. This study was designed to elucidate the clinical and metabolic characteristics of the prevalence of hypertension in adults and to explore the risk factors and interactions among these factors in adults with hypertension. METHODS: We used overall random sampling to conduct a cross-sectional survey of 6660 individuals undergoing a health check from July to November 2012, the subjects were aged 20 to 89 years, including 3480 men and 3180 women. The survey content included a questionnaire, anthropometry, laboratory measurements, and liver Doppler ultrasonography. The clinical and metabolic characteristics were compared between the cases (adult hypertensive patients) and the controls (normotensives). The classification tree model and the non-conditional logistic regression were used to analyze the interactions of risk factors for hypertension in adults. RESULTS: In total, 1623 adult hypertensive patients (940 men and 683 women) were detected. The results showed that adult hypertensive patients were older and had higher levels of systolic blood pressure, diastolic blood pressure, body mass index, fasting plasma glucose, uric acid, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and prevalence of non-alcoholic fatty liver disease (P < 0.001). The classification tree model comprising 5 layers, 39 nodes, and 20 terminal nodes showed that two variables, age and BMI, were closely related to hypertension in adults. The area under the receiver operating characteristic curve for classification tree model was 81.6 % (95 % CI: 80.6 % ~ 82.5 %). Both univariate and multivariate logistic regression analyses revealed that advanced age and high BMI had a significant positive interaction in terms of hypertension in adults. After controlling for confounding factors, the percentage of attributed interaction was 47.62 %. CONCLUSIONS: This study showed that age, BMI, UA, TG, and TC were closely associated with the risk of hypertension in adults, and the positive interaction effect between advanced age and high BMI was an important risk factor for the prevalence of hypertension in adults. PMID- 27663796 TI - Bipolar Disorder and Early Affective Trauma. AB - BACKGROUND: Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease. METHODS: Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review. RESULTS: 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. CONCLUSIONS: Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. In further studies attention should be paid to the age of trauma occurrence and the definition of trauma. The findings also support the importance of additional psychoanalytic oriented psychotherapy for the treatment of bipolar disorder. PMID- 27663797 TI - An approach to treat bipolar disorders mixed states. AB - Very often clinicians meet great difficulties in making a correct diagnosis of mood disorders which they are assessing, above all when mixed states are present: this because the patients mainly focus on their own symptoms of depressive uneasiness; mixed symptoms can insidiously infiltrate into the mood and life of the patients causing a chronic and worsening clinical state. It is essential not to forget that the depression is only one phase of a broader bipolar mood disorder, and this has to be the illness to be treated by psychiatrists and, generally, by clinicians managing an appropriate polytherapy with mood stabilisers and antidepressants. PMID- 27663798 TI - Risk and efficacy in cognitive functions in Bipolar Disorder II with atypical antipsychotic augmentation. AB - BD-II has been consistently associated with cognitive dysfunction across a broad range of cognitive domains. Atypical antipsychotic drugs, or SGAs are effective antipsychotics in these diseases, often in combination with antidepressants and mood stabilizers. Data on the possible effect of antipsychotics on neuro cognition are rare and conflicting. The main objective of our study was to assess the effectiveness and possible risks to cognitive function in a group of inpatients affected by BD-II. Forty-five inpatients with Bipolar II Disorder (DSM 5) were included in a two-year observational study. They were treated with sodium valproate as a mood stabiliser, atypical antipsychotics and SSRIs. The utilized SGA augmentation were quetiapine (n=13); aripiprazole (n=10); olanzapine (n=11); asenapine (n=11). All inpatients were administered some psychopathological scales and evaluated for neuropsychological variables (for example, attention, verbal memory domains, etc.). After two years of treatment with SGAs, there has been no significant reduction of previous levels. In particularly, quetiapine and asenapine groups showed a better performance in learning task, short-term task and recognition tasks, in accordance with previous studies. Our small observational study shown that atypical antipsychotics cause an improvement in symptoms in BD, and particularly BD II. In particular, they do not induce significant alterations in overall cognitive performance generally. On the contrary, some SGAs, such as quetiapine and asenapine, seem to demonstrate a not statistically significant mild improvement in cognition. PMID- 27663799 TI - Should Assessment for Bipolar Disorder and mixed affective state be a standard part of assessment for suicide risk? AB - The risk of suicide is high amongst individuals with bipolar affective disorder and mixed affective state. Research has shown that the suicide risk increases during both rapid-cycling and mixed affective states in bipolar. This article reviews the recent research of patients with bipolar and mixed affective state and suicide risk and highlights the reasons and potential benefits of factoring the potential risks into the assessment for suicide risk. PMID- 27663800 TI - Cardiovascular diseases in Patients with Bipolar disease: Pragmatic Management. AB - BACKGROUND: Bipolar disorder (BD), also known as manic-depressive illness, is a condition characterized by unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks. Bipolar disorder is known to be a chronic and disabling disease associated with higher incidence of obesity, diabetes, metabolic syndrome, dyslipidemias, hypertension and tobacco use which all together are known risk factors for the development of Cardiovascular diseases. With this research we wish to collect evidence to show how Cardiovascular diseases (CVD) affect Patients with Bipolar disease, the burden it can have in patients lives, to understand how this problem has been assessed so far and present suggestions that may improve the health care of these patients. METHODS: Our study is a literature based research. CONCLUSION: With our study we concluded that patients with BD are at higher risk of CVD and at an earlier age compared with the general population. Also, there is a lack of proper monitoring and consideration of the cardiovascular risk factors in patients with Bipolar disorder whether by primary care physicians or psychiatrists even though it plays a critical role in the general outcome of this patients and also leads to increase in mortality and morbidity rates. PMID- 27663795 TI - PRKCQ promotes oncogenic growth and anoikis resistance of a subset of triple negative breast cancer cells. AB - BACKGROUND: The protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCtheta, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCtheta is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCtheta critically regulates growth and survival of a subset of TNBC cells. METHODS: To elucidate the role of PRKCQ/PKCtheta in regulating growth and anoikis resistance, we used both gain and loss of function to modulate expression of PRKCQ. We enhanced expression of PKCtheta (kinase-active or inactive) in non-transformed breast epithelial cells (MCF-10A) and assessed effects on epidermal growth factor (EGF) independent growth, anoikis, and migration. We downregulated expression of PKCtheta in TNBC cells, and determined effects on in vitro and in vivo growth and survival. TNBC cells were also treated with a small molecule inhibitor to assess requirement for PKCtheta kinase activity in the growth of TNBC cells. RESULTS: PRKCQ/PKCtheta can promote oncogenic phenotypes when expressed in non-transformed MCF-10A mammary epithelial cells; PRKCQ/PKCtheta enhances anchorage-independent survival, growth-factor-independent proliferation, and migration. PKCtheta expression promotes retinoblastoma (Rb) phosphorylation and cell-cycle progression under growth factor-deprived conditions that typically induce cell cycle arrest of MCF-10A breast epithelial cells. Proliferation and Rb phosphorylation are dependent on PKCtheta-stimulated extracellular signal-related kinase (Erk)/mitogen-activated protein kinase (MAPK) activity. Enhanced Erk/MAPK activity is dependent on the kinase activity of PKCtheta, as overexpression of kinase-inactive PKCtheta does not stimulate Erk/MAPK or Rb phosphorylation or promote growth-factor-independent proliferation. Downregulation of PRKCQ/PKCtheta in TNBC cells enhances anoikis, inhibits growth in 3-D MatrigelTM cultures, and impairs triple-negative tumor xenograft growth. AEB071, an inhibitor of PKCtheta kinase activity, also inhibits growth and invasive branching of TNBC cells in 3-D cultures, further supporting a role for PKCtheta kinase activity in triple negative cancer cell growth. CONCLUSIONS: Enhanced PRKCQ/PKCtheta expression can promote growth-factor-independent growth, anoikis resistance, and migration. PRKCQ critically regulates growth and survival of a subset of TNBC. Inhibition of PKCtheta kinase activity may be an attractive therapeutic approach for TNBC, a subtype in need of improved targeted therapies. PMID- 27663801 TI - Does the increased rate of schizophrenia diagnosis in African-Caribbean men in the UK shown by the AESOP study reflect cultural bias in healthcare? AB - INTRODUCTION: The UK-based AESOP study conducted over a two-year period in three UK sites simultaneously (London, Nottingham, and Bristol), is the largest study to date to conduct a first contact case-control study of psychosis. The study found that rates of schizophrenia were markedly elevated in both African Caribbean and Black African people, in both sexes and across all age groups. SUBJECTS AND METHODS: English language literature published up to 2016 was searched. The initial search included: PubMed, The Cochrane Library, and Web of Science. A second search was conducted using Medical Subject Headings (MeSH) and keywords. Studies selected for retrieval were assessed by two independent reviewers. RESULTS: The search yielded eight results, all of which supported the conclusion of an increased incidence of schizophrenia in Black African and Black Caribbean population in the AESOP study. CONCLUSION: England is a multicultural landscape; multiplicity of cultures makes diagnosis difficult. The lessons we must learn from the AESOP study is the need for transcultural training and the removal of blinding to ethnicity when a large epidemiological study is conducted psychiatrists need to be cognisant of cultures and aware of the context of symptoms. PMID- 27663803 TI - Psychopathological characteristics of patients with first-episode psychosis and chronic schizophrenia: a descriptive comparison. AB - Only few studies have compared the psychopathological features in first episode psychosis (FEP) and chronic schizophrenia (CS) patients. The aim of our study was to compare sociodemographic and clinical aspects of FEP and CS inpatients using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) in order to better characterize FEP. We did not find significant socio-demographic differences between the two groups apart from age and nationality. About PANSS we found that conceptual disorganization, poor rapport and lack of insight items scores were significantly higher in patients with FEP. Related to BPRS the items of somatic concerns, grandiosity and motor hyperactivity were significantly higher in the CS group; uncooperativeness was significantly higher in FEP group. Our study offers a characterization of FEP patients that confirms evidence and adds some information from the current literature. FEP patients seem to be more uncooperative with a worse interpersonal empathy and insight into the illness than CS patients; this could reduce their compliance with the treatment. PMID- 27663802 TI - An update on: meta-analysis of medical and non-medicaltreatments of the prodromal phase of psychotic illness in at risk mental states. AB - INTRODUCTION: There are now many existing studies which assess the treatments available for 'at risk mental states', as patients who are believed to be in the prodromal phase of psychotic illness are referred to. However, concerns regarding side effects of possible treatments remain. We here conduct a meta-analysis of the studies available up to July 2016. The aim of this study is to decide what would be the best treatment for 'at high risk patients'. RESULTS: 18 studies were selected for inclusion; 12 showed significance, 5 did not and one tended towards significance. Both antipsychotic medication and psychological intervention show mixed results with cognitive behavioral therapy and olanzapine/amisulpride coming out on top. Omega 3 poly-unsaturated acid also shows promising and consistent results. DISCUSSION: Treatments appear promising but a balance needs to be kept between adverse events and effectiveness of preventing psychosis. CONCLUSION: It is necessary to search further for treatments in order to identify effective treatments with fewer adverse side-effects in this phase of psychotic illness. PMID- 27663804 TI - The role of selective estrogen receptor modulators in the treatment of schizophrenia. AB - BACKGROUND: Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention - the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). METHODS: This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. RESULTS: Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. CONCLUSIONS: SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects. PMID- 27663805 TI - Understanding the prevalence of 'legal high' misuse in early adulthood. AB - With the recent introduction of the Psychoactive Substances Bill in the United Kingdom, it is a useful time to retrospectively review the patterns of prevalence of the psychoactive products known as 'Legal Highs'. There has been emerging research and rapidly expanding political, public and media attention and awareness, yet comparatively little scientific discourse on the psychological aspects driving their consumption, beyond simply their legal status. This paper focuses on their usage patterns in the particularly vulnerable, but often neglected period of young adulthood between the ages of 16-24, focussing on their prevalence, trends in pharmacology and psychological aspects of their usage and propensity for addiction. There is a greater skew of usage to young adulthood in legal highs than that seen in classical drugs of abuse. Although there are still significant research questions to be tackled, it is suggested that the interaction of legal high incentive value and their perception with aspects of enhanced risk taking in young adulthood, particularly impulsivity and sensation seeking, are of key significance, as opposed to any clear pharmacological mechanism for differing prevalence. While there is much further research to be performed on the contents and pharmacology of legal highs, the reasons for potentially lower levels of addiction are also discussed. PMID- 27663806 TI - Gaming as a Therapeutic Tool in Adolescence. Experience of Institutional Therapy of CThA, UCL, Brussels, Belgium. AB - BACKGROUND: This work presents the experience of an Emancipatory action research led at the Therapeutic Center for Adolescents (CThA) at Saint Luc's Clinics (UCL). SUBJECT AND METHODS: This research focuses on the practice effects of "Pixels" and "Passerelle" workshops at CThA. It is about the use of video games as a therapeutic tool, mobilizing of the symptomatology of the teenager. RESULTS: "Pixels" workshops use playing according to three specific forms: the paper role play game, the video game, and the cards playing game. Their specificity is that the participative adult shows a regressive ability strong enough to play with teenagers and is very careful to not interpret what takes place within. CONCLUSIONS: "Passerelle" workshops demonstrate the link between the teenager's mind and the use of his own virtual avatar. It allows to evolve from a "play together" to a "talk together", a moment of symbolization and of being able to stand back in regards to his or her own recreational activities. As a discussion, this clinical illustration of Karl recovering from depression and dependency. This setting for speech allowed him to evolve into an impulse mood and to reconnect emotionally. PMID- 27663807 TI - New perspectives in Child and Adolescent Psychiatry. AB - Mental and behavioural problems during childhood and adolescence are a serious public concern and are increasing actually and in the next 10 years. In Belgium, policymakers have reorganize mental health care for children and adolescents in care circuits and care network that include and support intersectoral collaborations. They also support creation of mobile out-reach team for crisis and assertive care to help patient and their families in the least restrictive environment possible. Specific programs are developed for double diagnosis and disabled children but also juvenile offenders with psychiatric problems. The care network should also assure a rapid liaison function to the first line professionals. PMID- 27663808 TI - News in early intervention in autism. AB - BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental trouble which prevents the child from socio-communicative interaction, and learning from his environment. Non-medical early intervention attempts to improve prognosis. We will review the main current hypothesis, intervention models and scientific supports about early intervention. METHODS: We conducted a search of the literature published on Medline between 2010 and 2015 related to intervention models provided to children with ASD aged less than 3 years. Data were extracted from systematic reviews and recent randomized controlled trials with moderate to high GRADE quality of evidence. RESULTS: Early intervention refers to brain plasticity theory. With the epidemiological studies of infant "at risk" there is an attempt to intervene earlier before full syndrome is present. Interventions tend to follow more on a developmental hierarchy of socio-communicative skills and to focus on the dyadic relation between the child and the caregivers to improve the core autistic symptoms. Over the last 6 years, there's been news and fine-tuned ways about early intervention, and more and more systematic evaluation. CONCLUSION: However, there are only few interventions which were evaluated in trial with a strong GRADE recommendation and all of them have methodological concerns. It is important to be cautious in recommendations for mental health politic, even if it is important to improve access to services for all children and their families, hence finance and design rigorous project in research. PMID- 27663809 TI - The Child "after": between maternal Depression and Transmission of the traumatism. AB - Born a little time after the death of his sister, our patient, Antoine, 13 years old, was suffering from severe obsessional compulsive disorders, which needed care in the hospital and adapted treatment. We tried to know if what we were led to observe by this adolescent could be explained by works and thoughts around the notion of substitute child. Building our thought on various theoretical approaches, including neurosciences, we tried to think the psychopathological signs of this patient by two ways. One is about the birth and the growth in the presence of depressed parents, and this since the pregnancy. The other one is about the necessity to deal with the traumatic story of the family, met by the parents, who are still facing it, that leads to the question of the transmission of the traumatism from the mother to the baby. Using the notion of maternal primary care, we proposed the term 'the child after', which appeared to us more able to represent the dynamic and the place really given to these children. This term could mean the question of an undone grief, a traumatism without temporality, and a relation between the mother and the child which seems to be uncertain because of the investment of the child as an impossible reparation of an unscarred loss. PMID- 27663810 TI - Stigma in Malta; A Mediterranean Perspective. AB - The aim of this paper to describe what Transcultural Psychiatry is. It attempts to describe stigma in Malta and how it comes about that the Mental Hospital in Malta is named for Our Lady of Mount Carmel and finally attempt to put Mount Carmel Hospital and its dedication within Maltese Culture and the culture of the Mediterranean. The paper demonstrates that to understand this, it is necessary to employ History, Anthropology, Theology, among other issues. Doing this also suggests that Malta has undergone a process of 'normalisation' regarding treatment of Mental Health Problems. PMID- 27663811 TI - Are SSRIs responsible for precipitating suicidal ideation in teenagers with 'subsyndromal' bipolar affective disorder who have been misdiagnosed with unipolar depression? AB - Concerns have recently been raised about a possible link between suicidal ideation and the use of SSRIs in teenagers diagnosed with unipolar depression, such that the USA FDA and UK CSM have issued warnings regarding the use of SSRIs in adolescents with depression. We investigated this phenomenon first by recognizing that the initial presentation of unipolar and bipolar depression may only differ in subtle ways and with the result being that a significant number of patients are misdiagnosed at the expense of patient outcomes. This is especially pertinent as patients with bipolar disorder have increased lifetime rates of suicide as compared with those patients with unipolar depression. The normal developmental trajectory of bipolar disorder often involves recurrent depressive episodes in early adolescence before the development of hypomanic/manic episodes. Therefore, a misdiagnosis of bipolar disorder as unipolar depression in teenagers could explain the failure of SSRIs to adequately treat depressive episodes. A suboptimal response to SSRIs and so a lack of control of the depression is a risk factor for suicide. One reason for this suboptimal response is the markedly different neurotransmission involved in bipolar depression as compared to the neurotransmitter systems operated on by SSRIs. In bipolar disorder, dopamine is the principal neurotransmitter disrupted and we marshal structural, pharmacological and biochemical evidence to support this claim. One important strand of evidence involves polymorphisms in D1 and D2 dopamine receptors being implicated in the pathogenesis of bipolar affective disorder. Serotonin neurotransmission is affected by SSRIs, however the role of serotonin in bipolar disorder is much more ambiguous. The conclusion we arrive at is that the link between suicidality and SSRI use in adolescents diagnosed with unipolar depression may in fact be due to inappropriate treatment of misdiagnosed bipolar disorder that has yet to manifest with hypomanic/manic symptoms. PMID- 27663813 TI - Childhood obesity: global issues. AB - The eating disorders are a group of situations which are very complex that include abnormal feeding patterns, too much worry about the physical aspect, no real perception of the body image and a strong link between all these factors and the levels of self-esteem (Fairburn & Harrison 2003, Sigel 2008, American Academy of Pediatrics 2010, Dalle Grave 2011). From the '50s of the previous century we had a continuous increase of the Eating Disorders (Dalle Grave 2011). Indeed, in the National Program of the Prevention is stated that: "The spread of the eating disorders is very fast and relevant; there is no other disease with the same propagation and that looks like a real social epidemic" (The Ministry of Health 2010). At the same time, there was a reduction of the time of onset (Favaro et al. 2009) with cases of girls 8/9 years old, before having their first period (Dalla Ragione 2012). This means that the pediatricians should pay more attention to the eating disorders because there is a big delay in the diagnosis that can have a negative impact on the therapy to apply and on the prognosis (American Academy of Pediatrics 2010). Overweight and eating disorders are the main problems of public health among adolescents and many works show a direct link between eating disorders and child obesity (Babio et al. 2009). In the case of children, the diagnosis is very complex, especially during the early adolescence (-12 years) due to the large heterogeneity of the somatic expressions that make difficult a precise nosographic study. Therefore, it is necessary that the pediatrician has a good knowledge about the eating disorders in order to identify them quickly and to start a multidisciplinary path and to promote an improvement in the long term. PMID- 27663812 TI - Social attitude towards mentally ill in comparison to experts' opinions. AB - BACKGROUND: In modern psychiatry, deinstitutionalization of mentally ill became an essential part of improving state of being of those affected. Integration in community, despite obvious benefits, led to increase in social distance and rejection towards mentally ill. Social stigma affects different life domains of those afflicted, and therefore it is crucial to introduce methods to deal with it. Our objective was to assess and compare psychiatrists' and public attitudes and beliefs about mentally ill people. MATERIALS AND METHODS: Comparison of two samples, one including 107 psychiatrists and second including 708 individuals of the general population. Obtained outcomes were collated with similar studies available in literature. OUTCOMES: The psychiatrists' attitude was more positive in comparison to the general population. Both groups agree that programs raising public awareness are important, and should be intensified. 41% of general population and 13% of respondents from experts' group think of negative associations with mentally ill. CONCLUSIONS: Conception of utilizing mental health experts as the opinion leaders should be carefully thought through. Although awareness of social distance and stigma improved both among psychiatrists and general population since 2005 (Wciorka & Wciorka 2006, Lauber 2004), still there are areas that needs enhancement. Fear present in both groups, probably caused by inter allia image of mental illness in news reports (Angermeyer 2001), is one of such areas. PMID- 27663814 TI - The social networks: new challenge or new addiction? AB - The reality of Social networks provides a fascinating and enhancing opportunity to understand the issues and life dynamics of generations of pre-adolescents and adolescents; This study has matured over three years of work in the schools of Campania (southern Italy), observing all the provinces, with a predominance of those of the Neapolitan territory. It has been found that the language of the boys finds its maximal expression in using social media to share, exhibit, and tell their experience of living every day their daily lives, with a high probability of encountering very interesting pitfalls and dangers... because they are "children" of a period when to exhibit themselves is in accordance with current fashion. These dangers and pitfalls are amplified by simply sharing, and sharing this work with professionals has helped to better monitor some contexts and difficulties which have emerged with difficulty and have helped to shed light on more specific and authentic issues regarding this reality. PMID- 27663815 TI - Assessment and management of major depressive disorder in older adults. AB - BACKGROUND: Major depression disorder (MDD) is one of the most common mental disorders world-wide and is prevalent throughout the lifespan, with prevalence estimates of 1-5% in those 65 years of age and older. METHODS: The aim of this mini-review is to briefly summarize clinically relevant topics within the domain of later-life MDD. RESULTS: The mini-review presents an overview of epidemiology, complications of late life MDD, risk factors and clinical presentation, clinical assessment, general issues relevant to the treatment of the older adult with MDD, drug treatments, discussion of how medical complexity affects drug treatment and other treatment modalities. CONCLUSION: The mini-review concludes with a short discussion of clinical and research implications. Treatment of depression in the geriatric population is a complex endeavor and clinicians often are faced with medical, social, and environmental issues which can impede the treatment process. Antidepressant drugs, particularly the SSRI and SNRI antidepressants are helpful, but dosing titration needs to be considered against the backdrop of comorbidity and concomitant medications. Psychotherapy and other approaches are additional avenues to consider in the older individuals with MDD. Future research in particular needs to address older people with more extensive medical complexity as well as the "oldest-old", individuals in their 80's and beyond. PMID- 27663816 TI - Investigative and therapeutic uses of Transcranial magnetic stimulation (TMS) in Attention Deficit Hyperactivity Disorder (ADHD). AB - Attention Deficit Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that affects children and young adults. It results in significant impairment of their educational, social and occupational functioning and is associated economic societal burden. Whilst there are effective medications (such as methylphenidate) as well as some psychobehavioural therapies that can help with management of symptoms of ADHD, the former can have significant cardiac side effects, which limit their use. For number of patients these treatment options lack efficacy or are not acceptable. There is need to improve our understanding of neurobiology of ADHD as well as explore other treatment options. Transcranial magnetic stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) are safe and non-invasive investigative and therapeutic tools respectively. In this short paper, I will explore the potential role of TMS and rTMS in further improving our understanding of the neurobiology of ADHD as well as possible treatment option. PMID- 27663817 TI - CBT/DBT skills training for adults with attention deficit hyperactivity disorder (ADHD). AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is associated with marked impairments in familial, social, and professional functioning. Although stimulant treatments can be effective in adult ADHD, some patients will respond poorly or not at all to medication. Previous studies demonstrated that cognitive behavioural therapy- (CBT) and dialectical behavior therapy- (DBT) oriented interventions are effective in reducing the burden of the disease, which is mainly marked by depression, interpersonal difficulties, low self-esteem, and low quality of life. In order to determine the effectiveness of this intervention, we assessed the benefits of a CBT/DBT programme to reduce residual symptoms and help patients improve their quality of life. SUBJECTS AND METHODS: 49 ADHD-patients, poor responders to medication, were enrolled in a one-year programme where they received individual therapy, associated with weekly sessions of group therapy with different modules: Mindfulness, Emotion Regulation, Interpersonal Effectiveness and Distress Tolerance, Impulsivity/Hyperactivity and Attention. Each subject was assessed at baseline, at months 3 and 6, and at the end of the treatment for ADHD severity (ASRS v1.1), depression severity (BDI-II), hopelessness (BHS), mindfulness skills (KIMS), anger expression and control (STAXI), impulsivity (BIS-11), quality of life (WHOQOL-BREF), and social functioning (QFS). The 49 ADHD patients were compared with 13 ADHD subjects on a waiting list. Linear mixed models were used to measure response to treatment. RESULTS: Overall, the psychotherapeutic treatment was associated with significant improvements in almost all dimensions. The most significant changes were observed for BDI-II (b=-0.30; p<0.0001), ASRS total score (b=-0.16; p<0.0001), and KIMS AwA (b=0.21; p<0.0001), with moderate to large effect sizes. Compared with the waiting list controls, ADHD patients showed a better, albeit non-significant, pattern of response. CONCLUSIONS: Individual and structured psycho-educational DBT/CBT groups support existing data suggesting that a structured psychotherapeutic approach is useful for patients who respond partially or not at all to drug therapy. PMID- 27663818 TI - Epidemiology of Serious Mental Illness in Malta - Consequences for developing a new psychiatric hospital and community psychiatry. AB - Mental Health Services in Malta are presently at crossroads, because they are in the stage of increasing and strengthening the community services and considering closing the main psychiatric inpatient facility and replacing it with a new hospital. For proper planning of such changes, and ideal approach is that of basing these plans on results of population based epidemiological findings on rate of mental illness and required care. Such studies are strongly recommended, and this approach has already been used in Malta a couple of years ago prior to establishing inpatient care for Eating Disorders. In absence of such studies, this paper proposes ways how to use findings from available research and data to use as basis for such proper service plans. PMID- 27663819 TI - The new functional identity: a body that thinks, a mind that feels - Frontiers and unexplored territories of the "Body and Mind zone". AB - For a long time, terms like "mind" and "emotion" have rarely been taken into account, not even mentioned in the medical texts. The latest scientific researches, including the studies of Candace Pert, on the contrary, have emphasized that the entire body thinks, because every single cell hears, and feels emotions. The international researcher has discovered the endocrines and a vast number of neuropeptides, that work as an "information network" that interconnects the entire body, the "psychic" molecules are transmitted and travel, communicating information as in a circular and recursive body - mind mechanism. This is a sort of body and mind functional identity, which is different in each person, because each person is a unique universe, and the body is the place where mind and body meet in a unique and unrepeatable alchemy. So, if it is true that only in the body the secret of its potential for development and transformation is well hidden, it is also true that this secret is unique for each of us. Then, the strategic therapy becomes 'tailor-made', and the knowledge of the body component is essential to unlock behavior patterns and planning new ones, in order to improve relationships and the quality of life, and enhance the sense of well-being. People are not as simple containers which merely record external incitements, on the contrary, they are able to evaluate and weigh what happens around. Depending on the meaning attributed to each stimulus, a stress response of different magnitude and duration is activated, this can be considered functional or dysfunctional. Many recent studies, in fact, states that there is a significant correlation between the coping strategy chosen and the onset of a disease. According to the theory of 'psychogenic tumor', for example, anyone can potentially develop cancer, but only those who do not have the psychological strength to resist disease get sick. No matter what is the theoretical framework and the conclusion adopted, we go towards a consensus of considering body and mind as a part of a unique and complex functional identity. As a consequence of this completely new approach on how to consider the wellbeing and health, researchers suggest that the goal of a satisfactory physical and mental balance can be achieved through a transversal approach to the various disciplines (psychotherapy, surgical, nutritionist, medical aesthetics and medicine in general). According to this bio-psycho-social approach, each person should be approached in his entirety, bodily and psychological; each individual should be 'hosted' in a sort of 'Body and Mind' zone, where the entire body is able to think. PMID- 27663820 TI - Implementation of the MOTEK CAREN system in behavioural therapy for patients with anxiety disorders. AB - BACKGROUND: Virtual reality exposure therapy (VRET) is becoming a more and more popular treatment method for patients suffering from anxiety disorders. One of the VRET methods, wchich could be used for this group of patients is MOTEK CAREN system, however, so far no studies have been published on its implementation in psychiatric disorders. SUBJECT AND METHODS: Presented here is a case of a 45 year old woman suffering from anxiety disorders, who underwent a series of four subsequent trainings with the use of MOTEK CAREN system repeted once a week. Data from the system were collected on the work of muscles, joints, reactions of the ground, etc. Blood pressure, pulse and salivary cortisol level were measured before and after each training. The level of state and trait anxiety was each time measured with the STAI inventory. RESULTS: The changes of the values of heart rate, blood pressure and salivary cortisol suggest that all trainings we stressful events for the patients, as they were not observed in the control session. But the gradual decrease in the levels of salivary cortisol and axiety as state after subsequent trainings may be signs of a gradual adaptation of the patient to the stressful situation. A lower cadence during the trainings compared to the control session was observed, however the speed of the cadence increased with each session. CONCLUSIONS: Ttrainings with the MOTEK CAREN system can be promising in the treatment of anxiety disorders. Of course in order to draw more evidence based conclusions this observations must be confirmed on a larger sample of patients. PMID- 27663821 TI - Liaison psychiatry and bariatric surgery: double standards. What are the possibilities for the systematization of the pre-operative psychiatric assessment in Belgium? AB - BACKGROUND: In the context of health care in Belgium, the psychological or psychiatric opinion of a multidisciplinary team is required in the assessment of bariatric surgery candidates. In clinical practice, a wide variety of liaison psychiatry assessment methods exist. SUBJECTS AND METHODS: On the basis of a post operative psychiatric comorbidity case report and a literature review on "liaison psychiatry and bariatric surgery" we aim to identify opportunities for the systematization of bariatric pre-surgery psychiatric evaluation. RESULTS: The bariatric pre-surgery evaluation must be rigorous and founded on evidence-based medicine. On this basis, specific psychiatric criteria may be defined and researched in assessments. The issue remains for psychiatric comorbidities that develop after surgery and for which a preventive framework should be sustained in the liaison psychiatry approach. CONCLUSIONS: The aim of the research is to support an improved systematization of the psychological assessments of pre operative bariatric surgery candidates. We believe that systematic evaluation tools should be defined for the identification of possible absolute or relative contra-indications and that a preventive approach to post-operative psychiatric disorders should be included in this assessment. PMID- 27663822 TI - Thinking of psychiatric disorders as "normal" illness. Data from a questionnaire on social stigma: a multicenter study. AB - Prejudice and stigma about mental illness is still present in society. Patients suffer both from the disease, and from the marginalization behavior exhibited by others towards them and their families. Psychiatric professionals may also become ill and suffer for the same reason. The authors of this international multicenter study have set themselves the question of whether there may be prejudice and/or stigma among psychiatric professionals towards their suffering colleagues, among patients towards nursing staff affected by the same disease and between patients themselves. Using two standardized questionnaires which have been tested, but have not been used before they have studied 207 mental health professionals and 407 patients, of Italian, Belgian, Hungarian and Croatian nationalities. The results show that there are in fact prejudices among Mental Health Professionals about colleagues suffering from mental illness because they responded that such persons cannot treat well patients with their own pathology. However Mental Health Professionals do not demonstrate behaviors which are not frankly marginalizing or stigmatizing towards colleagues suffering from mental illness. On the other hand, among patients the prevailing view was that psychiatric professionals who suffer from mental illness, can better understand the sick, because they are also suffering. This is in analogy with the Jungian theory of the "wounded healer" in the myth of the centaur Chiron. Patients did not demonstate rejection or marginalization behavior towards other sick patients. Finally both the professionals and the patients tend to be cautious in relating to healthy persons and tend not to disclose their suffering for fear of being misjudged or marginalized. PMID- 27663823 TI - Social welfare in Mental Health Department for a Good clinical practice. AB - The National Plan of Action for Mental Health (PANSM), approved by the Conference of Regions has been from January 24 2013, being implemented by the Department of Mental Health Services. It requires a reorganization of the same, the functional the adoption of a methodology based on the Necessity of Working for projects which are Intervention-specific and differentiated, based on the evaluation of the need and patients and the implementation of care pathways. This implies a systemic approach by of the team, rather than a segmental working mode. Thus change is necessary in the work culture of the teams, and from the State Regions Conference November 13 2014, has emerged the need to share, among all stakeholders, good practices and the development of Clinical Management Tools so that standards of care can be defined to ensure quality, together with the measurement of Processes and Outcomes. PMID- 27663824 TI - Drugs in Alzheimer's disease Dementia: An overview of current pharmacological management and future directions. AB - BACKGROUND: Alzheimer's dementia is one of the most significant health burdens of the modern age in both industrialised and non-industrialised nations as it is a major cause of morbidity and functional impairment in the elderly. Currently there are no cures for progressive dementias, including Alzheimer's disease, and no treatments that would modify their progress. Intervention involves pharmacological treatment to temporarily relieve the symptoms, including three cholinesterase inhibitors and a noncompetitive NMDA antagonist, and the efficacy of these is widely debated. While our understanding of the underlying pathology of Alzheimer's continues to grow, we have yet to fully elucidate the mechanisms that drive neuronal loss in this condition. Any truly disease-modifying treatment must be developed to target these pathological pathways. METHODS: An extensive analysis of the available literature is presented here, including a number of trials, meta-analyses and reviews, with the aim of assessing current management, establishing best practice and summarising the future of dementia care. RESULTS: The efficacy of acetylcholinesterase inhibitors remains controversial due to uncertainty over what change is considered clinically significant. Any derived benefit seems to be independent of dementia severity and donepezil is the most cost-effective for Alzheimer's dementia. Memantine potentially influences the underlying pathological processes in Alzheimer's disease and may be more effective in moderate to severe Alzheimer's dementia. The role of combination therapy remains uncertain. Future therapies are aimed at modulating the disease process by using chemical agents to inhibit amyloid and tau deposition. None have been approved clinically. CONCLUSIONS: Current pharmacological therapy for Alzheimer's dementia is very limited and primarily aims at achieving symptom control. A major limitation is our lack of knowledge of the underlying pathology and it is only by better understanding the disease process that we can optimize therapeutic agents that modify disease progression. PMID- 27663825 TI - Pharmacogenetics: does a personal therapy exist? AB - Pharmacogenetics is a powerful tool to improve drug response and to maximize therapeutic efficacy and safety using genetic information of each individual. This review collects the available literature understanding the influence of heritability on an individual's drug metabolism. PMID- 27663826 TI - Neurocognitive management of the primary negative symptoms of schizophrenia: a role of atypical antipsychotics. AB - Patients with schizophrenia have profound and disabling cognitive deficits while negative symptoms represent a separate symptom domain, with respect to depression, neurocognition, and social cognition. Particularly, primary negative symptoms of schizophrenia represent a diagnostic and therapeutic challenge, In this study we try to evaluate the cognitive symptoms in 51 primary negative schizophrenic inpatients by the administration of simple, fast and understandable scales (MMSE, DSST, EpiTrack, PANSS cognitive factor). We also evaluate the correlation with some SGAs (aripiprazole, quetiapine, olanzapine, paliperidone). Our results support the evidence of the use of simple, rapid and acceptable scales for cognitive evaluation in clinical practice. Overall data indicate no statistically significant variations of the negative symptomatology in all the examined sample, although a reduction of the statistical averages in each group is observed (paliperidone and olanzapine, particularly). PMID- 27663827 TI - Treatment of Depression in patients with Osteoarthritis: the importance of an early diagnosis and the role of Duloxetine. AB - BACKGROUND: Osteoarthritis (OA) also called degenerative joint disease is the most common chronic condition of the joints that just in 2004, caused moderate to severe disability in 43.4 million of people. OA in Western populations is one of the most frequent causes of joint pain, loss of function and disability in adults. In the U.S. it is the second most common cause of work disability in men over 50 years of age, following ischaemic heart disease, and accounts for a higher number of hospitalizations when compared with rheumatoid arthritis (RA) each year. This condition is associated with chronic pain (which can be severe in many cases) and long term inflammatory processes which all together represent conditions that are known to be associated with depression. Depression is among the most burdensome disorders worldwide having affected just in 2010 15.4 million adults worldwide. Depression is associated with increase of symptom burden, greater level of functional impairment and increased risk of both disease complications and mortality. With this research we wished to put in evidence the importance of an early diagnosis of Depression in patients with osteoarthritis by using PHQ9 and suggest Duloxetine as an antidepressant that can be helpful in the management of not only pain but also depression in OA patients. METHODS: Our study is a literature based research. CONCLUSION: Early Diagnosis of depression of patients with osteoarthritis appears to be crucial for improving the outcomes of patients with OA and that can be easily and efficiently done with PHQ9. Duloxetine presents itself as an ally in the fight against the evolution of depression in patients with OA and should be considered even in mild to moderate states of depression. PMID- 27663828 TI - Megadose bromazepam dependence. AB - BACKGROUND: Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries. Since BZDs can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZDs causes a number of serious side effects, i.e. cognitive impairment, falls, traffic accidents, dependence and tolerance. METHODS: We present the case of a 37 years old woman taking daily doses of 220 mg of bromazepam. The patient's anxiety, depression and cognitive status were evaluated with a battery of questionnaires. A sleep laboratory test was performed in search of sleep apneas and sleepiness during the day. A Cerebral PET SCAN was executed in search of altered cerebral metabolism. RESULTS: Blood concentrations of bromazepam reached 7800 MUg/L. Questionnaire evaluations showed significant depression and anxiety but only moderate cognitive impairment. Oxygen saturation was normal throughout the Sleep lab test, respiratory events were very few and sleepiness was moderate with an average latency of 9 minutes. Brain cortical glucose consumption was homogeneously slightly reduced. CONCLUSIONS: With doses of bromazepan reaching 15 times the toxic dose, anxiety remained high. Cognition, sleepiness, respiratory sleep events and brain metabolism remained remarkably close to normal. PMID- 27663829 TI - Comparison of components of the depression of hospitalized patients admitted through the emergency department or consultations. AB - BACKGROUND: In a previous study, we investigated the risk of admission to emergency (ER) of depressed patients prior to their hospitalization in psychiatry in comparison with hospitalized patients transferred from the consultations department (Cdpt). In the present study, we compare among the same patients variables affecting the intensity of depression in each group. METHOD: All patients with Major depressive disorder admitted in our department through emergencies (N=146) or consultations (N=2172) between January 1, 2010 and December 31, 2012 were included in an open study. They completed the Beck Depression Inventory (BDI), analogical visual scales about stress levels (in professional, social, family, married life, over the past year and the past month), the Multidimensional Health Locus of Control and the Olson Family Adaptation and Cohesion Scale and the Ways of coping. RESULTS: The depression (t=1.438; p=0.90) is similar in both samples. Although some variables such as gender, internality, coping mechanisms and stress factors influence the intensity of depression in both groups of patients (linear regression p<0.000, r=0.593), other factors play a role only in either one or the other group. The factors of patients' age, number of children, elements of family dynamics, couple life, and the belief in luck do influence the intensity of depression only in patients hospitalized through Cdpt (linear regression p<0.000, r=0.366). The intensity of depression of patients admitted through ER, is specifically dependent on the number of collateral factors (p=0.045, r=0.304), the number of living relatives (p=0.036, r=0.276) and the belief in the power of others (p=0.022, r=-0.16). CONCLUSIONS: Although Both samples are comparable in terms of intensity of depression, patients admitted through the Cdpt are more dependent on the quality of family relationships whereas those coming from emergencies are most influenced by their concrete social and family situation. Alongside these specific variables it remains that stress and coping mechanisms account for the largest percentage of variance of the intensity of depression. PMID- 27663830 TI - Evaluation of the cortisol concentrations in patients with schizophrenia. AB - INTRODUCTION: The hypothalamus-pituitary-adrenal axis (HPAA) plays a pivotal role in response to a range of external and internal factors often described as a "stress". Growing evidence in a literature, suggest various dysregulations of HPAA, in course of numerous mental disorders. Patients with schizophrenia and bipolar disorder seem to have elevated basal cortisol secretion, what might be caused by the diminution of glucocorticoid receptors' amount. It was of the interest if the cortisol concentrations in patients with diagnosed schizophrenia who underwent treatment, differs from healthy individuals. MATERIALS AND METHODS: Two groups of participants were included into the study. First group (study) consisted of 10 patients with diagnosed schizophrenia and control group which included 38 healthy individuals. Study was divided into two stages, first one (pilot) included only control group, and utilized cortisol concentrations measurement from saliva, blood and 24h urine sample. Second part (main study) involved both groups although focused on a salivary cortisol concentrations. RESULTS: A mean salivary cortisol concentration in patients with schizophrenia who underwent treatment was significantly lower in comparison with healthy individuals. CONCLUSIONS: Obtained results indicate that patients who underwent a treatment, and does not present notable clinical signs of schizophrenia may have moderately lowered levels of salivary cortisol. This may be a reflection of relenting psychotic symptoms as well as a direct effect of atypical antipsychotic drugs on a HPA axis activity. PMID- 27663831 TI - Immunity, coping and depression. AB - BACKGROUND: On the one hand, this psycho-immunological theory makes it possible to forge links between immunity and depression. On the other hand, we know that coping strategies are an important variable in the model of vulnerability to depression. Our study weighs the influence of cellular immunity and coping strategies on the severity of depression. SUBJECTS AND METHOD: 498 inpatients with major depressive disorder were enrolled in an open-label trial. In addition to a socio-demographic questionnaire, they answered a Cousson's coping test and the Beck Depression Inventory (BDI). RESULTS: In terms of immunity, there are correlations between the BDI and percentages of CD8 (p=0.000; r=0.163), CD19 (p=0.046; r=0.090), CD16&56 (p=0.011; r=0.282), ratio CD4/CD8 (p=0.003; r= 0.135). A linear regression model for immune variables explained 25% of the BDI. In terms of coping, there is a correlation between severity of depression and ea (escape avoidance) (p=0.000; r=0.218), pr (positive reappraisal) (p=0.000; r= 0.265) and pps (planful problem solving) (p=0.000; r=-0.296). However, there is no correlation between the severity of depression and d (distancing). A linear model for coping strategies explained 12% of the BDI. Finally, there are correlations between distancing and CD8 (p=0.005; r=-0.119), CD19 (p=0.017; r= 0.102) and CD 16&56 (p=0.029; r=-0.227) but also CD3 (p=0.008; r=-0.114) and CD4 (p=0.027; r=-0.095) but not between those immune variables and the other coping strategies. In this case, a linear regression for distancing explained 10.3% of immune variables. CONCLUSION: Every coping strategy has an impact on depression. But not in the same way. Ea, pps and pr strategies influence directly the risk of depression while distancing influences the immune variables themselves. Knowing that those variables impact the risk of depression, distancing has then an indirect effect on depression. PMID- 27663832 TI - Depression, family and immunity: influence of humoral immunity on family relationships and on the severity of depression. AB - BACKGROUND: Previous study shows that cellular immunity and family relationships are each correlated with the severity of depression and suggests that the psycho immunological theory should look at the relation between immunity and family life. The aim of the present study based on the same sample is to investigate if similar correlations exist with humoral immunity. SUBJECTS AND METHOD: 498 inpatients with major depressive disorder were enrolled in an open-label trial. In addition to a socio- demographic questionnaire, they completed Olsen's FACES III and the Beck Depression Inventory (BDI). We performed a classic blood test, a plasma cortisol assay at 8 a.m., 4 p.m. and 8 p.m. and a dexamethasone suppression test (Carroll test). Electrophoresis is used for separation and quantification of serum proteins. RESULTS: There is no correlation between humoral immunity and the severity of depression. We found a correlation between cohesion of the family of the origin and beta-globulins (r=-0.147; p=0.016), and C4 (r=0.124; p=0.039). Between adaptability of the family of the origin and cortisol levels at 8 a.m. (r=0.122; p=0.008). We showed a correlation between both C4 (r=-0.263; p=0.000) and beta-globulins (r=-0.148; p=0.013) with CD8. There is a correlation between cortisol at 8 a.m. and CD4 (r=-0.095; p=0.033). CONCLUSIONS: Humoral immunity has no correlation with depression but has multiple interactions with cellular immunity which is correlate with the severity of the depression. The psycho-immunological theory is reinforced. It is quite original to find correlation between the family functioning and C4 or beta-globulins while the link with cortisol strengthens some studies about psychological stress, cortisol and immunity. Future studies should examine which kind of family or relation are implicated and how the family functioning and immunity could be connected. PMID- 27663833 TI - Ways of coping and multidimensional health locus of control in hospitalized depressed patients admitted through the emergency department or consultations. AB - BACKGROUND: In a previous study, we compared the family relationships of patients hospitalized in a psychiatry unit from either psychiatric consultations or after passing emergency room (E.R.). The intensity of depression was statistically comparable in both groups. What distinguishes patients transiting emergencies is that their families and couples are more cohesive and adaptable. In this study, we compare both groups in terms of coping mechanisms and multidimensional health locus of control (MHLC). SUBJECTS AND METHODS: All patients (N=2172) with a major depressive disorder admitted to our department between 01/01/2010 and 31/12/2012 are included in an open study. They completed the Beck's Depression Inventory, the Olson's Family Adaptability and Cohesion Scale, visual analogue scales of stress, the ways of coping checklist, and the MHLC scale. RESULTS: Patients admitted through emergencies are found to have less belief in chance (CHLC) (t=2.488; p=0.014), distance themselves more from their problems (t=-2.187; p=0.03), but reappropriate them less positively (t=2.355; p=0.019) than those admitted through consultations. A logistic regression model including variables identified in the previous study (adaptability in the original family and the couple's lived stress) gives a risk factor (odds ratio) of 14.7 which means that a patient who would combine the different risk factors would be 14.7 times more likely to go through emergency. CONCLUSIONS: How to explain that depressive patients with more favorable factors considered: to believe less in chance, distancing from their problems, and having a better family support, are more likely to go to the E.R.? We make the suggestion that those factors exactly slowed down patients in their care application at first, allowing the depression to worsen. It is only once they would have depleted their reserves that they would reach the emergency room on their own initiative or encouraged by their families, themselves overwhelmed by the situation. Further study should take into account the duration of the episode before arrival at the hospital. PMID- 27663834 TI - Depression, gender and cellular immunity: influence of gender and severity of depression on the cellular immunity. AB - BACKGROUND: Exposure to stress modifies the humoral and cellular immunity by the activation of the hypothalamic-pituitary-adrenal axis. On one hand, this psycho immunological theory allows the analyse of links between immunity and depression. On the other hand, the correlation between the immune response, the clinical expression in major depressive disorder (MDD) and the gender was proven. Our analysis evaluates the influence of the gender and the level of depression severity on the cellular immune response associated with it. SUBJECTS AND METHOD: 549 patients with MDD were enrolled in an open-ended survey. In addition to a socio-demographic questionnaire, they completed the Beck Depression Scale (BDS). Flow cytometry was used to assess lymphocyte subsets. RESULTS: On average, the intensity of the depression (ID) among women is higher by 2.9 points (t=2.379*). In terms of immunity, there are correlations between this ID and absolute values of CD3 (r=-0.127***), CD4 (r=-0.189***), CD8 (r=0.089*) and CD16 and 56 (r=0.129*). In terms of gender, there are significant differences for the percentage of total lymphocytes (m=37.84, w=35.59; t=2.646***), CD3 (m=2.08, w=1.9; t=2.676*), CD4 (m=1.44, w=1.3; t =2.522*), CD8 (m=0.62, w=0.57; t=2.182*). A linear regression model including both variables supports the existence of these differences in the percentage of total lymphocytes (Adjusted R2=0.025***) and CD8 (Adjusted R2=0.012*). CONCLUSIONS: If the link between depression and the cellular immune response is a known fact, our study proves that women have a stronger immune response than men in terms of percentage of total lymphocytes mobilized and cytotoxic lymphocytes. The volume of natural killer lymphocytes is independent of the gender but connected to the ID. Based on those results, psycho immunological theories could potentially be rethought in the light of immunity being at least partially dependent of the gender. PMID- 27663835 TI - Towards Process-based Range Modeling of Many Species. AB - Understanding and forecasting species' geographic distributions in the face of global change is a central priority in biodiversity science. The existing view is that one must choose between correlative models for many species versus process based models for few species. We suggest that opportunities exist to produce process-based range models for many species, by using hierarchical and inverse modeling to borrow strength across species, fill data gaps, fuse diverse data sets, and model across biological and spatial scales. We review the statistical ecology and population and range modeling literature, illustrating these modeling strategies in action. A variety of large, coordinated ecological datasets that can feed into these modeling solutions already exist, and we highlight organisms that seem ripe for the challenge. PMID- 27663836 TI - What is a Trophic Cascade? AB - Few concepts in ecology have been so influential as that of the trophic cascade. Since the 1980s, the term has been a central or major theme of more than 2000 scientific articles. Despite this importance and widespread usage, basic questions remain about what constitutes a trophic cascade. Inconsistent usage of language impedes scientific progress and the utility of scientific concepts in management and conservation. Herein, we offer a definition of trophic cascade that is designed to be both widely applicable yet explicit enough to exclude extraneous interactions. We discuss our proposed definition and its implications, and define important related terms, thereby providing a common language for scientists, policy makers, conservationists, and other stakeholders with an interest in trophic cascades. PMID- 27663837 TI - Development and validation of a novel single nucleotide polymorphism (SNP) panel for genetic analysis of Blastomyces spp. and association analysis. AB - BACKGROUND: Single nucleotide polymorphism (SNP) genotyping is increasingly being utilized for molecular typing of pathogens and is cost-effective, especially for large numbers of isolates. The goals of this study were 1) to develop and validate a SNP assay panel for genetic analysis of Blastomyces spp., 2) ascertain whether microsatellite genotyping and the SNP genotyping with the developed panel resolve identical genetic groups, and 3) explore the utility of SNPs for examining phylogenetic and virulence questions in humans. METHODS: Three hundred sixty unique Blastomyces spp. isolates previously genotyped with microsatellite markers were genotyped with the MassARRAY(r) SNP genotyping system (Agena BioscienceTM, San Diego, CA), for a custom panel of 28 SNPs. Clinical presentation data was analyzed for association with SNP variants. RESULTS: Three hundred twenty-three Blastomyces spp. isolates (90 %) were successfully genotyped by SNP analysis, with results obtained for at least 27 of 28 assays. For 99.7 % of isolates tested by both genotyping methods, microsatellite genetic group assignment correlated with species assignment based on internal transcribed spacer 2 (ITS2) genotyping, with Group 1 (Gr 1) being equivalent to B. gilchristii and Group 2 (Gr 2) being equivalent to B. dermatitidis. Thirteen isolates were genetic hybrids by one or both methods of genotyping and were difficult to assign to a particular genetic group or species. Fifteen SNP loci showed significantly different alleles in cases of pulmonary vs disseminated disease, at a p-value of <0.01 or less. CONCLUSIONS: This study is the largest genotyping study of Blastomyces spp. isolates and presents a new method for genetic analysis with which to further explore the relationship between the genetic diversity in Blastomyces spp. and clinical disease presentation. We demonstrated that microsatellite Gr 1 is equivalent to B. gilchristii and Gr 2 is equivalent to B. dermatitidis. We also discovered potential evidence of infrequent recombination between the two Blastomyces spp. Several Blastomyces spp. SNPs were identified as associated with dissemination or pulmonary disease presentation, but additional work is needed to examine virulence SNPs separately within B. dermatitidis and B. gilchristii. PMID- 27663838 TI - Antimicrobial peptides (AMPs): Ancient compounds that represent novel weapons in the fight against bacteria. AB - Antimicrobial peptides (AMPs) are short peptidic molecules produced by most living creatures. They help unicellular organisms to successfully compete for nutrients with other organisms sharing their biological niche, while AMPs form part of the immune system of multicellular creatures. Thus, these molecules represent biological weapons that have evolved over millions of years as a result of an escalating arms race for survival among living organisms. All AMPs share common features, such as a small size, with cationic and hydrophobic sequences within a linear or cyclic structure. AMPs can inhibit or kill bacteria at micromolar concentrations, often by non-specific mechanisms; hence the appearance of resistance to these antimicrobials is rare. Moreover, AMPs can kill antibiotic resistant bacteria, including insidious microbes such as Acinetobacter baumannii and the methicillin-resistant Staphylococcus aureus. This review gives a detailed insight into a selection of the most prominent and interesting AMPs with antibacterial activity. In the near future AMPs, due to their properties and despite their ancient origin, should represent a novel alternative to antibiotics in the struggle to control pathogenic microorganisms and maintain the current human life expectancy. PMID- 27663840 TI - Identification of a novel canine parvovirus type 2c in Taiwan. AB - BACKGROUND: Taiwan has been considered free from canine parvovirus type 2c (CPV 2c) based on the last report of canine parvovirus type 2 (CPV-2) surveillance. However, since January 2015, the first report of CPV-2c in a puppy has occurred in Taiwan. There is currently limited information about the CPV-2c variant in Taiwan. In the present study, we characterized the previously unidentified CPV-2c variant and investigated the distribution of CPV-2 variants in Taiwan. METHODS: During January 2014 to April 2016, fecal or rectal swab samples from 99 dogs with suspected CPV-2 infection in Taiwan were collected. Eighty-eight were identified as being either CPV-2a, -2b or -2c variants positive by real-time PCR and sequence analysis. RESULTS: Sequence analysis of the 88 isolates confirmed CPV-2c as the dominant variant (54.6 %), followed by CPV-2b (26.1 %) and CPV-2a (19.3 %). Phylogenetic analysis demonstrated that the recent CPV-2c variants are similar to the Chinese CPV-2c strain but can be considered as novel Asian CPV-2c isolates. CONCLUSION: The present study provides evidence for the existence of a novel CPV-2c variant in Taiwan. PMID- 27663839 TI - RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1,6-nonadien-3-ol, CAS Registry Number 10339-55-6. AB - The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the suitable read across analog linalool (CAS # 78-70-6) show that this material is not genotoxic nor does it have skin sensitization potential and also provided a MOE > 100 for the local respiratory endpoint. The repeated dose, developmental and reproductive toxicity endpoints were completed using nerolidol (isomer unspecified, CAS # 7212-44-4) as a suitable read across analog, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework. PMID- 27663841 TI - Exogenous apelin changes alpha and beta myosin heavy chain mRNA expression and improves cardiac function in PTU-induced hypothyroid rats. AB - The most important conditions associated with hypothyroidism is the cardiac dysfunction. Apelin is an endogenous ligand, involved in energy storage and metabolism which improves cardiac contractility. This study was done to evaluate the effects of apelin, l-Thyroxin (T4) or a combination of both, on cardiac function and mRNA expression of two contractile proteins, alpha and beta myosin heavy chain (alpha-MHC and beta-MHC), in 6-propyl-2-thiouracil (PTU)-induced hypothyroid rats. Forty male Wistar rats were randomly assigned into five groups: Ctrl (Control), and 4 hypothyroid groups (H, HA, HT, and HAT). The Hypothyroid (H) group received 0.05% PTU in the drinking water for six weeks; the next 3 groups, along with PTU, received apelin (HA, 200MUg/kg/day, ip), T4 (HT, 20MUg/kg/day, gavage), or a combination of both drugs (HAT) for the last 2weeks (weeks 5 and 6). TSH and T4 were measured using ELISA kit. Isolated hearts of animals were perfused in Langendorff apparatus and left ventricular developed pressure, cardiac contractility, heart rate, rate pressure product and perfusion pressure were assessed using PowerLab ADInstruments. In addition alpha-MHC and beta-MHC mRNA expression were evaluated by RT-PCR method in heart tissue. Apelin alone or accompanied by T4 significantly increased cardiac contractility and performance as compared to hypothyroid group. Apelin also significantly increased the alpha-MHC mRNA expression and in the presence of T4 significantly decreased beta-MHC mRNA expression. It seems that apelin alone may improve cardiac function in hypothyroid rats via genomic pathways. PMID- 27663842 TI - Anthropic influences on the sedimentation rates of lakes situated in different geographic areas. AB - The aim of this study is to determine the effects of natural and anthropic events occurring in the last 30 years in the catchment areas of four Romanian lakes (St. Anna Lake, Red Lake, Varsolt Lake and Matita Lake) originating from four different geomorphologic areas. A total of eleven sediment cores have been processed for age and sedimentation rate determination using the 210Pb dating method. Total 210Pb was measured via alpha spectrometry by 210Po using PIPS detectors, while supported 210Pb was measured by 226Ra using HPGe detectors. Ages and sedimentation rates were calculated using the CRS model. The values of the sedimentation rates have grown multiply in the last three decades: 2.66 times in case of the St. Anna Lake (from 0.06 +/- 0.01 g/cm2y to 0.16 +/- 0.02 g/cm2y), up to 6.72 times in case of Red Lake (0.36 +/- 0.04 g/cm2y to 2.42 +/- 0.36 g/cm2y), 4.02 times in case of Varsolt Lake (04 g/cm2y to 1.53 +/- 0.18 g/cm2y) and up to 16.18 times in case of Matita Lake (0.27 +/- 0.03 g/cm2y to 4.37 +/- 0.32). PMID- 27663843 TI - Barriers, enablers and challenges to initiating end-of-life care in an Australian intensive care unit context. AB - BACKGROUND: Patients admitted to Australian intensive care units are often critically unwell, and present the challenge of increasing mortality due to an ageing population. Several of these patients have terminal conditions, requiring withdrawal of active treatment and commencement of end-of-life (EOL) care. OBJECTIVES: The aim of the study was to explore the perspectives and experiences of physicians and nurses providing EOL care in the ICU. In particular, perceived barriers, enablers and challenges to providing EOL care were examined. METHODS: An interpretative, qualitative inquiry was selected as the methodological approach, with focus groups as the method for data collection. The study was conducted in Melbourne, Australia in a 24-bed ICU. Following ethics approval intensive care physicians and nurses were recruited to participate. Focus group discussions were discipline specific. All focus groups were audio-recorded then transcribed for thematic data analysis. RESULTS: Five focus groups were conducted with 11 physicians and 17 nurses participating. The themes identified are presented as barriers, enablers and challenges. Barriers include conflict between the ICU physicians and external medical teams, the availability of education and training, and environmental limitations. Enablers include collaboration and leadership during transitions of care. Challenges include communication and decision making, and expectations of the family. CONCLUSIONS: This study emphasised that positive communication, collaboration and culture are vital to achieving safe, high quality care at EOL. Greater use of collaborative discussions between ICU clinicians is important to facilitate improved decisions about EOL care. Such collaborative discussions can assist in preparing patients and their families when transitioning from active treatment to initiation of EOL care. Another major recommendation is to implement EOL care leaders of nursing and medical backgrounds, and patient support coordinators, to encourage clinicians to communicate with other clinicians, and with family members about plans for EOL care. PMID- 27663844 TI - Regulatory Forum Opinion Piece: Review-Toxicological Pathology Profile and Regulatory Expectations for Nonclinical Development of Insulins and Insulin Analogues. AB - The toxicological profile of insulins is exclusively due to exaggerated pharmacology resulting in hypoglycemic findings. Insulin analogues displaying modifications and aimed at improving pharmacokinetics do not induce different toxicity. The main target is the brain displaying neuronal necrosis. Wallerian degeneration of nerves occurs rarely after severe hypoglycemia. These findings are of potential human relevance; nevertheless, these changes are induced in normoglycemic animals whereas diabetic patients suffer from hyperglycemia. Therefore, it is usually not difficult to achieve a therapeutic window for subsequent use in patients. Based upon this and in the absence of classical toxicity, there has been no scientific need for diabetic animal models. A greater challenge is the mitogenicity already inherent with regular insulin. Thus, the focus for preclinical safety evaluation of analogues is to demonstrate that modifications in regular insulin do not result in enhanced mitogenicity. The approaches used to assess the mitogenic potential of insulin analogues have changed over time driven by scientific progression and changes within the regulatory environment. Therefore, in vitro and in vivo evaluation of cell proliferation has become common practice, and to date there has been no evidence that the mitogenic potential of insulin analogues may be increased compared to regular insulin. PMID- 27663846 TI - Tofacitinib for the treatment of tumor necrosis factor-alpha inhibitor refractory esophageal Crohn's disease: a case report. AB - BACKGROUND: Esophageal Crohn's disease is reported as a rare manifestation, although its prevalence may be underestimated because upper endoscopies are not routinely performed in asymptomatic adults. Tofacitinib, an oral janus kinase inhibitor, is a new biologic that has shown promise in the treatment of ulcerative colitis and may be effective in the treatment of Crohn's disease according to phase 2 trials. We report the first case of esophageal Crohn's disease successfully treated with tofacitinib in a patient with worsening symptoms despite maintenance therapy with a tumor necrosis factor-alpha inhibitor. CASE PRESENTATION: A 67-year-old Caucasian woman presented with new dysphagia and had findings of esophageal Crohn's disease on endoscopy. The dosage of her current biologic therapy-adalimumab-was increased in frequency, without improvement. Our patient was started on tofacitinib and demonstrated an improvement in symptoms, with a repeat endoscopy showing resolution of the previous lesions. CONCLUSION: Esophageal Crohn's disease is likely underdiagnosed but is an important consideration in a patient with new symptoms of dysphagia and known Crohn's disease. Tofacitinib, while a novel agent, could have a role in the treatment of esophageal Crohn's disease that does not improve with intensification of the current biologic therapy. It provides a different mechanism in patients who become refractory to maintenance therapy. PMID- 27663845 TI - High muscular fitness has a powerful protective cardiometabolic effect in adults: influence of weight status. AB - BACKGROUND: Low levels of muscular fitness (MF) are recognized as an important marker of nutritional status and a predictor of metabolic complications, cardiovascular disease and death, however, the relationship between MF, body mass index (BMI) and the subsequent cardiometabolic protective effects has been less studied among Latin American populations. This study identified an association between MF and the cardiometabolic risk score index (CMRSI) and the lipid metabolic cardiovascular risk index (LMCRI) in a wide sample of university students grouped according to their BMI. METHODS: Six thousand ninety five healthy males (29.6 +/- 11.7 year-old) participated in the study. Absolute strength was measured using a T.K.K. analogue dynamometer (handgrip), and the participant's strength was then calculated relative to their body mass (MF/BM). The LMCRI was derived from the levels of triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and glucose levels in a blood sample. The CMRSI was calculated by summing the standardized residuals (z-score) for waist circumference, total cholesterol, LDL-c, triglycerides, HDL-c, and median blood pressure. Subjects were divided into six subgroups according to BMI (normal vs. overweight/obese) and MF/BM tertiles (unfit, average, fit). RESULTS: The group of participants with low and moderate levels of MF/BM showed higher CMRSI values independent of BMI (P < 0.001). The group with normal BMI and high MF/BM had the highest levels of cardiometabolic protection. All overweight/obese BMI groups had significantly higher LMCRI values independent of the level of MF/BM (P < 0.001). CONCLUSIONS: Participants with high MF/BM showed reduced cardiometabolic risk, which increased significantly when they were within normal parameters. PMID- 27663849 TI - Application of a framework for the selection of an appropriate occupational exposure limit for manganese. AB - Occupational exposure limits (OELs) serve as benchmarks for the interpretation of workplace exposures within a health risk context. Different organizations derive OELs for many chemicals, including manganese. OELs recommended by different organizations can vary quantitatively, which can present a challenge to occupational hygienists or other risk managers that need to select a value for decision-making purposes. In this article, we illustrate the application of a previously-developed OEL selection framework to demonstrate the decisions that would be required to select the most appropriate OEL for various manganese exposure scenarios. The framework helped to identify the need to focus an evaluation on three quantitatively similar values-the ACGIH TLV, SCOEL IOELV, and DFG MAK. These values were compared with regulatory standards and considered for their relevance and reliability. The OEL selection framework was a useful tool in guiding the selection process for manganese OELs. PMID- 27663848 TI - Structure-activity relationship for the anticonvulsant effects of organic solvents. AB - Several organic solvents have anticonvulsant or convulsant actions depending on the dose and exposure time. To study if there is a structure-activity relationship for organic solvents as anticonvulsant agents we subjected independent groups of mice to a single 30-min exposure session to inhale n hexane, cyclohexane, benzene (8000ppm each), toluene (500-6000ppm), m-xylene (1000-6000ppm), ethylbenzene (500-4000ppm) or propylbenzene (500-4000ppm). Immediately after, animals were injected i.p. with 90mg/kg pentylenetetrazol (PTZ) and re-exposed to the same solvent for another 30min. During this time, the occurrence of seizures and death was recorded. n-Hexane and cyclohexane had no anticonvulsant effect. Benzene and alkylbenzenes delayed the onset of PTZ-induced seizures. In addition, all four alkylbenzenes decreased the number of animals that seized. Propylbenzene and ethylbenzene were equally effective, but more potent than toluene and m-xylene to block PTZ actions. In the second part of the study we exposed independent groups of mice to 8000ppm n-hexane, cyclohexane (solvents without effect in the PTZ experiment), 8000ppm benzene or 6000ppm toluene, m-xylene, ethylbenzene or propylbenzene following the same experimental protocol (i.e. 30-min exposure, injection, 30-min re-exposure), but using 120mg/kg NMDA as the convulsant agent. All aromatic compounds prevented NMDA lethal effects, but only benzene and toluene decreased the percentage of animals that seized. Taken together, our data suggest that the benzene ring alone or substituted with alkyl groups is necessary for the anticonvulsant effect of acute solvent exposure against seizures and/or death produced by PTZ or NMDA. PMID- 27663850 TI - Adult lead exposure increases blood-retinal permeability: A risk factor for retinal vascular disease. AB - Low-to-moderate level developmental and adult lead exposure produces retinal dysfunction and/or degeneration in humans and experimental animals. Although high level in vivo or in vitro lead disrupts blood-brain-barrier tight junctions and increases its permeability, the blood-retinal-barrier (BRB) has not been examined. There were four overall goals. First, generate environmentally relevant dose-response models of short-term lead exposure in adult rats. Second, assess retinal histology and functional integrity of the BRB. Third, investigate the transmembrane proteins occludin and claudin-5 as targets mediating the increased BRB permeability. Fourth, examine the contribution of the PI3K-Akt signaling pathway as a mechanism underlying increased BRB permeability. Young adult rats were given water, 0.01% or 0.02% lead drinking solutions for six weeks. In control, 0.01% and 0.02% groups the six week mean blood [Pb] were 1, 12.5 and 19MUg/dl, respectively. We employed histology, stereology, quantitative image analysis, immunoblots and densitometry, and pharmacology techniques. Major findings were that adult lead exposure produced dose-dependent 1) decreases in outer and inner nuclear layer thickness, 2) increases in BRB permeability, 3) decreases in occludin and claudin-5 expression, 4) increases in pAkt (Ser473), but not pAkt (Thr308), expression, and 5) wortmannin partially or completely blocked the increased BRB permeability and changes in protein expression. These results indicate that lead-induced increases in PI3K-Akt signaling partially underlie the increased BRB permeability and advance our knowledge about lead induced retinotoxicity. Furthermore, they suggest that environmental and occupational lead exposures are risk factors for increased BRB permeability in diseases such as age-related macular degeneration, diabetes and stroke. PMID- 27663851 TI - Changes in mental state and behaviour in Huntington's disease. AB - Changes in mental state and behaviour have been acknowledged in Huntington's disease since the original monograph in 1872 provided evidence of disinhibition and impaired social cognition. Behavioural problems can manifest before obvious motor symptoms and are frequently the most disabling part of the illness. Although pharmacological treatments are used routinely for psychiatric difficulties in Huntington's disease, the scientific evidence base for their use is somewhat sparse. Moreover, effective treatments for apathy and cognitive decline do not currently exist. Understanding the social cognitive impairments associated with Huntington's disease can assist management, but related therapeutic interventions are needed. Future research should aim to design rating scales for behaviour and mental state in Huntington's disease that can detect change in clinical trials. Generally, communication and understanding of behaviour and mental state in Huntington's would be enhanced by a clear conceptual framework that unifies ideas around movement, cognition, emotion, behaviour, and mental state, reflecting both the experience of the patient and their underlying neuropathology. PMID- 27663847 TI - Acute exposure to a Mn/Zn ethylene-bis-dithiocarbamate fungicide leads to mitochondrial dysfunction and increased reactive oxygen species production in Caenorhabditis elegans. AB - Mn/Zn ethylene-bis-dithiocarbamate (Mn/Zn-EBDC) fungicides are among some the most widely-used fungicides in the world. Although they have been available for over 50 years, little is known about their mechanism of action in fungi, or their potentially toxic mechanisms in humans. To determine if exposure of Caenorhabditis elegans (C. elegans) to a representative fungicide (Manzate; MZ) from this group inhibits mitochondria or produces reactive oxygen species (ROS), we acutely (30min) exposed worms to various MZ concentrations. Initial oxygen consumption studies showed an overall statistically significant decrease in oxygen consumption associated with addition of Complex I- and/or II-substrate in treatment groups compared to controls (*p<0.05). In order to better characterize the individual complex activity, further studies were completed that specifically assessed Complex II or Complex IV. Data indicated that neither of these two complexes were targets of MZ treatment. Results from tetramethylrhodamine ethyl ester (proton gradient) and ATP assays showed statistically significant reductions in both endpoints (*p<0.05, **p<0.01, respectively). Additional studies were completed to determine if MZ treatment also resulted in increased ROS production. These assays provided evidence that hydrogen peroxide, but not superoxide or hydroxyl radical levels were statistically significantly increased (*p<0.05). Taken together, these data indicate exposure of C. elegans to MZ concentrations to which humans are exposed leads to mitochondrial inhibition and concomitant hydrogen peroxide production. Since mitochondrial inhibition and increased ROS are associated with numerous neurodegenerative diseases, we suggest further studies to determine if MZ catalyzes similar toxic processes in mammals. PMID- 27663852 TI - Over-passage of epithelioma papulosum cyprini (EPC) cells increased viral hemorrhagic septicemia virus (VHSV) replication. AB - Vaccines based on inactivated or attenuated viruses can be a way to prevent viral hemorrhagic septicemia virus (VHSV) disease, and the efficiency of viral production is a critical factor that can determine the practical use of developed vaccines in aquaculture farms. To know the effects of epithelioma papulosum cyprini (EPC) cells over-subculture on VHSV replication, the VHSV titer produced from high-passage EPC cells (subcultured more than 200 times in our laboratory) was compared to the titer produced from low-passage EPC cells (subcultured 5-15 times). Furthermore, to know whether immune factors are involved in VHSV titers, differences not only in the expression of Mx1 and ISG15 genes but also in the apoptosis progression by VHSV infection between high- and low-passage EPC cells were analyzed. The VHSV titers from high-passage EPC cells were significantly higher than titers from low-passage EPC cells, suggesting that the changed properties of EPC cells by over-subculture were favorable for VHSV proliferation. The DNA laddering of high-passage EPC cells by VHSV infection took a longer time than that of low-passage EPC cells, suggesting that over-subculture might delay apoptosis in VHSV infected EPC cells, and the delay of apoptosis by over subculture can be thought as one of the factors that increased VHSV titers in high-passage EPC cells. The increased folds of Mx1 and ISG15 genes in high passage EPC cells were significantly lower than those in low-passage EPC cells when exposed to either poly (I:C) or VHSV. However, the expression levels of Mx1 and ISG15 genes of high-passage EPC cells that were not stimulated with poly I:C or VHSV were almost equal to or higher than the expression levels of low-passage EPC cells that were exposed to poly (I:C) or VHSV. This result suggests that high passage EPC cells were already in an excited state in type I interferon responses without any stimulants. The full open reading frame (ORF) sequences of Mx1 gene between high- and low-passage EPC cells were completely same. However, there were some differences in the amino acids sequences of ISG15 gene between high- and low passage EPC cells, suggesting that ISG15-mediated pathways might be different between high- and low-passage EPC cells, which might influence on the replication of VHSV. The present results showed that the changed properties of EPC cells by over-subculture were favorable for VHSV proliferation. PMID- 27663853 TI - Live recombinant Lactococcus lactis vaccine expressing immobilization antigen (i Ag) for protection against Ichthyophthirius multifiliis in goldfish. AB - The parasite Ichthyophthirius multifiliis (Ich) has been reported in various freshwater fishes worldwide and results in severe losses to both food and aquarium fish production. Lactobacillus strains have a number of properties that make them attractive candidates as delivery vehicles for the presentation to the mucosa of compounds with pharmaceutical interest, in particular vaccines. Here, the present study was conducted to evaluate a live recombinant Lactococcus lactis vaccine expressing immobilization antigen (IAG-52X) in protection against I. multifiliis. A 1266 bp gene fragment containing a potential antigenic epitope of the 48 kDa immobilization antigen of I. multifiliis was assembled from six synthetic ohgonucleotides and cloned into pSIP409 and electrotransformed into Lactobacillus plantarum NC8. The recombinant vaccine candidate was then orally fed into goldfish. The expression of immune-related genes: complement component 3 (C3), MHC I, IgM gene in blood from goldfish at different time points after immunization were evaluated. Immunized fish were than challenged with a lethal dose of infectious I. multifiliis. The cumulative mortality and relative percentage survival (RPS) were also determined. Our results showed that the antibody level in the blood and skin of the immunized fish was statistically significant (P < 0.05) in relation to the control groups. Goldfish orally immunized with NC8-pSIP409- IAG-52X had high serum antibody titers that ranged from 32 to 256 after 28d post immunization, while fish fed with NC8-pSIP409 or PBS had no detectable immobilizing antibody response. Expression of IgM, C3, MHC I genes in the group immunized with IAG-52X were significantly (P < 0.05) up regulated as compared with control group, indicating that different immune cells were actively involved in cellular immune response. The results showed that the average survival rate of fish orally immunized with 108 and 106NC8-pSIP409-IAG 52X was 60% and 50% respectively. Therefore, NC8-pSIP409-IAG-52X could become a promising oral vaccine candidate against I. multifiliis. PMID- 27663854 TI - Characterization of a hemocyte homeostasis-associated-like protein (HHAP) in the freshwater crayfish Pacifastacus leniusculus. AB - Hemocyte homeostasis-associated-like protein (HHAP) in the freshwater crayfish Pacifastacus leniusculus has a distinct role from that of its homolog PmHHAP in the shrimp Penaeus monodon. Knockdown of PlHHAP in vitro using double-stranded RNA (dsRNA) had no effect on the cell morphology of hematopoietic tissue (HPT) cells. The total hemocyte number and caspase activity were unchanged after PlHHAP knockdown in vivo, in contrast to the results found in shrimp. Moreover, suppression of PlHHAP both in vitro and in vivo did not change the mRNA levels of some genes involved in hematopoiesis and hemocyte homeostasis. Interestingly, bacterial count and scanning electron microscope revealed that depletion of PlHHAP in intestine by RNAi resulted in higher number of bacteria in the crayfish intestine. Together, these results suggest that PlHHAP is not involved in hemocyte homeostasis in the crayfish P. leniusculus but appears to affect the bacterial number in the intestine through an unknown mechanism. Since PlHHAP has different functions from PmHHAP, we therefore named it HHAP-like protein. PMID- 27663855 TI - Most mild chronic kidney disease is benign, GP study finds. PMID- 27663856 TI - Rapid screening for antibiotic resistance elements on the RNA transcript, protein and enzymatic activity level. AB - BACKGROUND: The emerging threat posed by antibiotic resistance has affected public health systems all over the world. Surveillance of resistant bacteria in clinical settings and identifying them in mixed cultures is of paramount importance and can contribute to the control of their spreading. Culture independent monitoring approaches are highly desirable, since they yield results much faster than traditional susceptibility testing. However, many rapid molecular methods like PCR only detect the sole presence of a potential resistance gene, do not provide information regarding efficient transcription, expression and functionality and, in addition, cannot assign resistance genes to species level in mixed cultures. METHODS: By using plasmid-encoded TEM beta lactamase mediated ampicillin resistances as a proof of principle system, we (1) developed a fluorescence in situ hybridization-test (FISH) capable to detect the respective mRNAs, (2) implemented an immunofluorescence test to identify the corresponding proteins and (3) compared these two microscopic tests with an established colorimetric nitrocefin assay to assess the enzymatic activity. RESULTS: All three methods proved to be suitable for the testing of antibiotic resistance, but only FISH and immunofluorescence were able to differentiate between susceptible and resistant bacteria on the single cell level and can be combined with simultaneous species identification. CONCLUSIONS: Fluorescence in situ hybridization and immunofluorescence tests are promising techniques in susceptibility testing since they bridge the gap between the slow, but accurate and sound cultural methods and molecular detection methods like PCR with much less functional relevance. PMID- 27663857 TI - [The most important current guideline recommendations on the topic urolithiasis : A brief comparison]. AB - For the development of patient-specific therapies the guidelines offer the physician a valuable catalogue of possible treatment options. They are based on the current level of knowledge and urological research, but also let some space for individual treatment at the same time. In this article, the current guidelines of several urological associations on the topic of urolithiasis regarding recommendations are described and the differences are highlighted. PMID- 27663858 TI - Can transcutaneous near infrared spectroscopy detect severe hepatic ischemia: a juvenile porcine model. AB - BACKGROUND: Vascular complications following pediatric liver transplantation occur in 8-10% of cases, and no continuous, non-invasive monitoring for this problem exists. Near infrared spectroscopy (NIRS) allows non-invasive, continuous, transcutaneous assessment of hemoglobin oxygenation (StO2 ) 1-4 cm below the skin surface. AIMS: We hypothesized that transcutaneous NIRS would be able to detect severe hepatic ischemia, and tested this in an animal model using 15-20 kg and 5-7 kg juvenile pigs. MATERIALS AND METHODS: Direct liver surface and transcutaneous hepatic tissue hemoglobin oxygen saturation (StO2 ) were measured during occlusions of the hepatic artery and portal vein. Changes in hepatic delivery of oxygen (HepDO2 ) were calculated for each ischemic challenge and compared to changes in direct liver surface (DirHepStO2 ) and transcutaneous liver StO2 measurements (CutHepStO2 ). RESULTS: In the 15-20 kg animals during complete occlusion, CutHepStO2 decreased by 6.0(+/-4.9)%, whilst DirHepStO2 decreased by 83.7(+/-7.2)%. In the 5-7 kg animals during complete occlusion, CutHepStO2 decreased by 27.4(+/-8.5)%, whilst DirHepStO2 decreased by 82.8(+/ 4.6)%. CONCLUSION: Transcutaneous hepatic StO2 monitoring cannot reliably detect severe hepatic ischemia in a juvenile porcine model, although a stronger and potentially useful signal is seen in 5-7 kg pigs. Trials of this technology should be currently restricted to situations where the organ is less than 1 cm from the skin surface, corresponding to infants of <10 kg. PMID- 27663859 TI - Simulation Modeling to Interpret the Captures of Moths in Pheromone-Baited Traps Used for Surveillance of Invasive Species: the Gypsy Moth as a Model Case. AB - When pheromone traps are used for detection of an invasive pest and then delimitation of its distribution, an unresolved issue is the interpretation of failure to capture any target insects. Is a population present but not detected, a so-called false negative? Using the gypsy moth (Lymantria dispar) as an exemplar, we modeled the probability of males being captured in traps deployed at densities typical for surveillance (1 per 2.6 km2 or 1 per mi2) and delimitation (up to 49 per 2.6 km2). The simulations used a dynamic wind model generating a turbulent plume structure and varying wind direction, and a behavior model based on the documented maneuvers of gypsy moths during plume acquisition and along plume navigation. Several strategies of plume acquisition using Correlated Random Walks were compared to ensure that the generated dispersions over three days were not either overly clumped or ranged many km. Virtual moths were released into virtual space with patterns mimicking prior releases of gypsy moth males in Massachusetts at varying distance from a baited trap. In general, capture rates of virtual and real moths at varying trap densities were similar. One application of this approach was to estimate through bootstrapping the probabilities of not detecting populations having densities ranging from 1 to 100 moths per 2.6 km2 and using traps that varied from 25 to 100 % in their efficiencies of capture. Low-level populations (e.g., 20-30 per 2.6 km2) often were not detected with one trap per 2.6 km2, especially when traps had low efficiencies. PMID- 27663861 TI - Lipid raft-associated stomatin enhances cell fusion. AB - Membrane fusions that occur during vesicle transport, virus infection, and tissue development, involve receptors that mediate membrane contact and initiate fusion and effectors that execute membrane reorganization and fusion pore formation. Some of these fusogenic receptors/effectors are preferentially recruited to lipid raft membrane microdomains. Therefore, major constituents of lipid rafts, such as stomatin, may be involved in the regulation of cell-cell fusion. Stomatin produced in cells can be released to the extracellular environment, either through protein refolding to pass across lipid bilayer or through exosome trafficking. We report that cells expressing more stomatin or exposed to exogenous stomatin are more prone to undergoing cell fusion. During osteoclastogenesis, depletion of stomatin inhibited cell fusion but had little effect on tartrate-resistant acid phosphatase production. Moreover, in stomatin transgenic mice, increased cell fusion leading to enhanced bone resorption and subsequent osteoporosis were observed. With its unique molecular topology, stomatin forms molecular assembly within lipid rafts or on the appositional plasma membranes, and promotes membrane fusion by modulating fusogenic protein engagement.-Lee, J.-H., Hsieh, C.-F., Liu, H.-W., Chen, C.-Y., Wu, S.-C., Chen, T.-W., Hsu, C.-S., Liao, Y.-H., Yang, C.-Y., Shyu, J.-F., Fischer, W. B., Lin, C. H. Lipid raft-associated stomatin enhances cell fusion. PMID- 27663863 TI - Bird brains: Does absolute size matter? AB - Kabadayi, Taylor, von Bayern, and Osvath (2016, Royal Society Open Science, 3, 160104) recently showed that among birds, absolute brain size predicts performance on a motor self-control task thought to be important for cognition. However, birds performed at an equivalent level to much larger-brained primates, opening up the debate about brain size and cognition. PMID- 27663860 TI - Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension. AB - The aim of this study was to investigate the in vivo role of angiotensin II type 1a (AT1a) receptor in renal damage as a result of hypertension by using transgenic mice with AT1a receptor gene disruption. Transgenic mice that express human liver-type fatty acid binding protein (L-FABP) with or without disruption of the AT1a receptor gene (L-FABP+/- AT1a-/-, and L-FABP+/- AT1a+/+, respectively) were used with urinary L-FABP as an indicator of tubulointerstitial damage. Those female mice were administered subcutaneously deoxycorticosterone acetate (DOCA)-salt tablets plus drinking water that contained 1% saline for 28 d after uninephrectomy. In L-FABP+/- AT1a+/+ mice that received DOCA-salt treatment, hypertension was induced and slight expansion of glomerular area, glomerular sclerosis, and tubulointerstitial damage were observed. In L-FABP+/- AT1a-/- mice that received DOCA-salt treatment, hypertension was similarly induced and the degree of glomerular damage was significantly more severe than in L-FABP+/- AT1a+/+-DOCA mice. Urinary L-FABP levels were significantly higher in L FABP+/- AT1a-/--DOCA mice compared with those in L-FABP+/- AT1a+/+-DOCA mice. Hydralazine treatment significantly attenuated renal damage that was found in L FABP+/- AT1a-/--DOCA mice along with a reduction in blood pressure. In summary, activation of the AT1a receptor may contribute to maintenance of the glomerular structure against hypertensive renal damage.-Hisamichi, M., Kamijo-Ikemori, A., Sugaya, T., Ichikawa, D., Natsuki, T., Hoshino, S., Kimura, K., Shibagaki, Y. Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension. PMID- 27663862 TI - Prediction of the efficacy of immunotherapy by measuring the integrity of cell free DNA in plasma in colorectal cancer. AB - We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA-A*2402-restricted CTL in combination with oxaliplatin containing chemotherapy (FXV study) as first-line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five-peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell-free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small-sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi-quantitative real-time PCR. Progression-free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA-A*2402-matched group, patients with a low plasma cfDNA integrity value had significantly better progression-free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA-A*2402-unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer. PMID- 27663864 TI - Part I--Comparing Noncancer Chronic Human Health Reference Values: An Analysis of Science Policy Choices. AB - The goal of this study was to systematically evaluate the choices made in deriving a chronic oral noncancer human health reference value (HHRV) for a given chemical by different organizations, specifically those from the U.S. Environmental Protection Agency, Health Canada, RIVM (the Netherlands), and the U.S. Agency for Toxic Substances and Disease Registry. This analysis presents a methodological approach for comparing both the HHRVs and the specific choices made in the process of deriving an HHRV across these organizations. Overall, across the 96 unique chemicals and 171 two-way organizational comparisons, the HHRV agreed approximately 26% of the time. A qualitative method for identifying the primary factors influencing these HHRV differences was also developed, using arrays of HHRVs across organizations for the same chemical. The primary factors identified were disagreement on the critical or principal study and differential application of the total uncertainty factor across organizations. Of the cases where the total UF was the primary factor influencing HHRV disagreement, the database UF had the greatest influence. PMID- 27663865 TI - Visual information about object size and object position are retained differently in the visual brain: Evidence from grasping studies. AB - Many experiments have examined how the visual information used for action control is represented in our brain, and whether or not visually-guided and memory-guided hand movements rely on dissociable visual representations that are processed in different brain areas (dorsal vs. ventral). However, little is known about how these representations decay over longer time periods and whether or not different visual properties are retained in a similar fashion. In three experiments we investigated how information about object size and object position affect grasping as visual memory demands increase. We found that position information decayed rapidly with increasing delays between viewing the object and initiating subsequent actions - impacting both the accuracy of the transport component (lower end-point accuracy) and the grasp component (larger grip apertures) of the movement. In contrast, grip apertures and fingertip forces remained well-adjusted to target size in conditions in which positional information was either irrelevant or provided, regardless of delay, indicating that object size is encoded in a more stable manner than object position. The findings provide evidence that different grasp-relevant properties are encoded differently by the visual system. Furthermore, we argue that caution is required when making inferences about object size representations based on alterations in the grip component as these variations are confounded with the accuracy with which object position is represented. Instead fingertip forces seem to provide a reliable and confound-free measure to assess internal size estimations in conditions of increased visual uncertainty. PMID- 27663866 TI - Upregulated microRNA-224 promotes ovarian cancer cell proliferation by targeting KLLN. AB - Human epithelial ovarian cancer is a complex disease, with low 5-yr survival rate largely due to the terminal stage at diagnosis in most patients. MicroRNAs play critical roles during epithelial ovarian cancer progression in vivo and have also been shown to regulate characteristic of ovarian cancer cell line in vitro. Alterative microRNA-224 (microRNA-224) expression affects human epithelial ovarian cancer cell survival, apoptosis, and metastasis. However, people know little about the effects of microRNA-224 on epithelial ovarian cancer cell proliferation. In the current study, we found that the microRNA-224 expression level of human syngeneic epithelial ovarian cancer cells HO8910 (low metastatic ability) was lower than that of HO8910PM (high metastatic ability). Furthermore, microRNA-224 was confirmed to target KLLN in HO8910 and HO8910PM. The known KLLN downstream target cyclin A was regulated by microRNA-224 in HO8910 and HO8910PM. In addition, overexpression of microRNA-224 enhanced the proliferation abilities of HO8910 and knockdown of microRNA-224 suppressed the proliferation abilities of HO8910PM by KLLN-cyclin A pathway. Our results provide new data about microRNAs and their targets involved in proliferation of epithelial ovarian cancer cells by modulating the downstream signaling. PMID- 27663867 TI - A neural marker of medical visual expertise: implications for training. AB - Researchers have identified a component of the EEG that discriminates visual experts from novices. The marker indexes a comprehensive model of visual processing, and if it is apparent in physicians, it could be used to investigate the development and training of their visual expertise. The purpose of this study was to determine whether a neural marker of visual expertise-the enhanced N170 event-related potential-is apparent in the EEGs of physicians as they interpret diagnostic images. We conducted a controlled trial with 10 cardiologists and 9 pulmonologists. Each participant completed 520 trials of a standard visual processing task involving the rapid evaluation of EKGs and CXRs-indicating-lung disease. Ostensibly, each participant is expert with one type of image and competent with the other. We collected behavioral data on the participants' expertise with EKGs and CXRs and electrophysiological data on the magnitude, latency, and scalp location of their N170 ERPs as they interpreted the two types of images. Cardiologists demonstrated significantly more expertise with EKGs than CXRs, and this was reflected in an increased amplitude of their N170 ERPs while reading EKGs compared to CXRs. Pulmonologists demonstrated equal expertise with both types of images, and this was reflected in equal N170 ERP amplitudes for EKGs and CXRs. The results suggest provisionally that visual expertise has a similar substrate in medical practice as it does in other domains that have been studied extensively. This provides support for applying a sophisticated body of literature to questions about training and assessment of visual expertise among physicians. PMID- 27663869 TI - Thermophoresis of cyclic oligosaccharides in polar solvents. AB - Cyclodextrins are cyclic oligosaccharides which are interesting as drug delivery systems, because they can be used as containers for pharmaceutical substances. We studied the Ludwig-Soret effect of [Formula: see text]-, [Formula: see text]-, [Formula: see text]- and methyl-[Formula: see text]-cyclodextrin in water and formamide by infrared thermal diffusion forced Rayleigh scattering (IR-TDFRS). In water the Soret coefficient, S T, of [Formula: see text]-, [Formula: see text]- and [Formula: see text]-cyclodextrin increases with increasing temperature and shows a sign change from negative to positive around T = 35 degrees C, while S T of methyl-[Formula: see text]-cyclodextrin is positive in the entire investigated temperature. In formamide S T-values of all cyclodextrins coincide and show a slight decrease with temperature. We discuss the obtained results and relate the S T-values to the different hydrogen bonding capabilities of the cyclodextrins and the used solvents. It turns out that the change of S T with temperature correlates with the partition coefficient, logP, which indicates that more hydrophilic substances show a more pronounced temperature sensitivity of S T. Additionally we obtained a surprising result measuring the refractive index contrast factor with temperature, [Formula: see text] of cyclodextrins in formamide, which might be explained by a complex formation between cyclodextrins and formamide. PMID- 27663870 TI - Flexible helical yarn swimmers. AB - We investigate the motion of a flexible Stokesian flagellar swimmer realised as a yarn made of two intertwined elastomer fibres, one active, that can reversibly change its length in response to a local excitation causing transition to the nematic state or swelling, and the other one, a passive isotropic elastomer with identical mechanical properties. A propagating chemical wave may provide an excitation mechanism ensuring a constant length of the excited region. Generally, the swimmer moves along a helical trajectory, and the propagation and rotation velocity are very sensitive to the ratio of the excited region to the pitch of the yarn, as well as to the size of a carried load. External excitation by a moving actuating beam is less effective, unless the direction of the beam is adjusted to rotation of the swimmer. PMID- 27663868 TI - Creation of a Virtual Anatomy System based on Chinese Visible Human data sets. AB - PURPOSE: Human anatomy learning confronts many difficulties, including the lack of anatomical specimens and limitations in anatomical dissection techniques that can destroy and change the shape and position of anatomic structures. A Virtual Anatomy System can help to overcome these difficulties. METHODS: Based on the high-resolution thin-sectional anatomical images of the Chinese Visible Human data set, we created a Virtual Anatomical System, including nearly all male and female anatomical structures. RESULTS: With this system, medical students can freely observe the detailed anatomical information of the coronal, sagittal, and transverse sections through a 3D-reconstructed realistic model on a personal computer in the local network. CONCLUSIONS: This Virtual Anatomy System is an easy and direct way for students to learn and understand the shape and the relationship of anatomic structures, which can also make the anatomy learning more interesting. Furthermore, it can help students synthetically master the anatomical knowledge. PMID- 27663871 TI - Shared decision-making in multiple sclerosis. AB - In a healthcare environment that is trying to achieve better clinical outcomes and patient satisfaction, shared decision-making is a well-established concept that is gaining more interest. Multiple sclerosis is a preference-sensitive condition and provides the opportunity to implement decision aids at various decision points in the disease process. Literature about patient education and outcomes of shared decision aids in multiple sclerosis has been growing over the last decade. In this topical review, we present an overview of the current literature on shared decision-making in multiple sclerosis. While limitations to the generalizability and applicability of decision aids exist, there is evidence that decision aids and shared decision-making can be valuable tools in the clinical care of multiple sclerosis patients. PMID- 27663872 TI - Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study. AB - BACKGROUND: Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. OBJECTIVES: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. METHODS: Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. RESULTS: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis ( p = 0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66-1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): -0.98, 95% CI: -2.05-0.15, p = 0.09). CONCLUSION: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome. PMID- 27663873 TI - Is Langerhans cell histiocytosis a neoplasia? PMID- 27663875 TI - Exposure to toxicants in soil and bottom ash deposits in Agbogbloshie, Ghana: human health risk assessment. AB - Recycling of e-waste using informal or crude techniques poses serious health risk not only to the workers but also to the environment as whole. It is against this background that this paper sought to measure health risk faced by informal e waste workers from exposure to toxicants such as lead, cadmium, chromium, copper, arsenic, tin, zinc and cobalt via oral and dermal contact with bottom ash and soil. Using random sampling techniques, 3 separate sites each (where burning and manual dismantling of e-wastes are usually carried) were identified, and a total of 402 samples were collected. The samples were analysed using standard methods for chemical analysis prescribed by the American Water Works Association (AWWA). Concentrations of Pb, Cd, Cr, Cu, As, Sn, Zn and Co in bottom ash samples from location ASH1 are 5388 +/- 0.02 mg/kg (Pb), 2.39 +/- 0.01 mg/kg (Cd), 42 +/- 0.05 mg/kg (Cr), 7940 +/- 0.01 mg/kg (Cu), 20 +/- 0.07 mg/kg (As), 225 +/- 0.04 mg/kg (Sn), 276 +/- 0.04 mg/kg (Zn) and 123 +/- 0.04 mg/kg (Co), while concentrations of the aforementioned toxicants in soil samples at location ASG1 are as follows: 1685 +/- 0.14 mg/kg (Pb), 26.89 +/- 0.30 mg/kg (Cd), 36.86 +/- 0.02 mg/kg (Cr), 1427 +/- 0.08 mg/kg (Cu), 1622 +/- 0.12 mg/kg (As), 234 +/- 0.25 mg/kg (Sn), 783 +/- 0.31 mg/kg (Zn) and 135 +/- 0.01 mg/kg (Co); used as input parameters in assessing health risk faced by workers. The results of cancer health risk faced by e-waste workers due to accidental ingestion of As in bottom ash at ASH1 is 4.3 * 10-3 (CTE) and 6.5 * 10-2 (RME), i.e. approximately 4 out of 1000 e-waste workers are likely to suffer from cancer-related diseases via central tendency exposure (CTE parameters), and 7 out of every 100 e-waste worker is also likely to suffer from cancer cases by reasonable maximum exposure (RME) parameters, respectively. The cancer health risk results for the other sampling sites were found to have exceeded the acceptable USEPA cancer risk value of 1 * 10-4 to 1 * 10-6 (i.e. 1 case of cancer per every 10,000 people to 1 case of cancer per every 1,000,000 people). The non-cancer health risk results for all the toxicants were higher in all the locations for both adult and children working the e-waste site. From the findings of this study, the government of Ghana has to immediately put in place policies that would address the safety of the e-waste workers as well as protect the environment. PMID- 27663874 TI - Relationships for mercury and selenium in muscle and ova of gravid freshwater fish. AB - At high concentrations, mercury (Hg) is toxic to vertebrates, causing neurological, behavioral, and teratological dysfunction. Selenium (Se) not only is an essential element but also has a high affinity for Hg, binding to organic methyl mercury at a molar ratio of Se/Hg of 1:1. Ratios of <1 increase risk of Hg toxicity. For gravid fish, low concentrations of Se in ova could increase potential for Hg toxicity, compromising embryonic development and fitness of fry. Mercury and selenium concentrations and ratios were investigated in the muscle and ovaries of six species from five families of fish to assess potential for risk to ecological fitness. Molar ratios of Se/Hg in muscle were typically >18 for lower trophic level species but <=2 for piscivores. For all species combined, the concentrations of Hg in ova were significantly related to concentrations of Hg in muscle. Concentrations of Se in ova versus muscle showed a similar significant relationship that was independent of muscle Hg concentration. Mean ova molar Se/Hg ratios were high, ranging from 69 to 955 for the 6 species. However, a declining relationship between the ova Se/Hg molar ratio and the muscle concentration of Hg for all species combined suggests that development of ova and fry might be compromised for those piscivores with the highest muscle Hg concentrations because of Hg-related Se deficiency. PMID- 27663876 TI - Rapid decadal evolution in the groundwater arsenic content of Kolkata, India and its correlation with the practices of her dwellers. AB - Increasing arsenic contamination in the groundwater is one of the biggest environmental challenges that the Bengal delta is facing today. Groundwater is still the main source of water for a large number of population in this region and therefore, significant presence of toxic arsenic has a direct consequence on human lives here. Moreover, arsenic also enters into the food chain through the consumed agricultural products grown in this area. Therefore, acquiring knowledge about the ever-changing map of arsenic contamination and employing adequate protective measures are of utmost importance. Here, we present a comprehensive municipal ward-wise map of the arsenic content of the shallow groundwater table of Kolkata-the most important and highly population dense city of the delta. Comparison with previously available data reveals a rapid change and the grim situation for the city. Our study suggests that it should be an immediate task of the administration to extend treated water service to the whole population of the city for direct consumption, and artificial recharge and maximum rainwater replenishment need to be taken up with utmost urgency to avoid intrusion of toxicity in biological food chains via agricultural products. We hope our study would drive the city planners to reconsider the existing urbanization and development plans of all the cities, placed over arsenic-contaminated groundwater aquifers. PMID- 27663877 TI - Differential BPA levels in sewage wastewater effluents from metro Detroit communities. AB - The endocrine disruptor Bisphenol A (BPA) is ubiquitous in both aquatic and surface sediment environments because it is continuously released into sewage wastewater effluent. The measurement of BPA at wastewater treatment plants is rarely performed even though the United States Environmental Protection Agency (EPA) states that current levels of environmental BPA could be a threat to aquatic organisms. Therefore, the aims of this study were to measure BPA levels in sewage wastewater at different collection points over a 1-year period and to compare the levels of BPA to 8-isoprostane, a human derived fatty acid, found in sewage wastewater. We analyzed pre-treated sewage samples collected from three source points located in different communities in the metropolitan Detroit area provided by the Detroit Water and Sewerage Department. Human urine samples were also used in the study. BPA and 8-isoprostane were measured using ELISA kits from Detroit R&D, Inc. BPA levels from the same collection point oscillated more than 10-fold over 1 year. Also, BPA levels fluctuated differentially at each collection point. Highly fluctuating BPA values were confirmed by LC/MS/MS. The concentration of BPA in sewage wastewater was ~100-fold higher than the concentration of 8-isoprostane, while urinary concentration was ~20-fold higher. Thus, BPA levels discharged into the sewage network vary among communities, and differences are also observed within communities over time. The difference in BPA and 8-isoprostane levels suggest that most of the BPA discharged to sewage wastewater might be derived from industries rather than from human urine. Therefore, the continuous monitoring of BPA could account for a better regulation of BPA release into a sewage network. PMID- 27663879 TI - Response to comments on "Microsurgical decompression for central lumbar spinal stenosis: a single-center observational study". PMID- 27663878 TI - Assessment of heavy metal pollution risks in Yonki Reservoir environmental matrices affected by gold mining activity. AB - This study reports the heavy metal (Hg, Cd, Cr, Cu, and Pb) contamination risks to and safety of two species of fresh water fish (tilapia, Oreochromis mossambicus and carp, Cyprinus carpio) that are farmed in the Yonki Reservoir in the Eastern Highlands of Papua New Guinea (PNG). The upper reaches of the reservoir are affected by alluvial and large-scale gold mining activities. We also assessed heavy metal levels in the surface waters and sediments and in selected aquatic plant species from the reservoir and streams that intersect the gold mining areas. The water quality was acceptable, except for the Cr concentration, which exceeded the World Health Organization (WHO) standard for water contamination. The sediments were contaminated with Cd and Cu in most of the sampling stations along the upstream waters and the reservoir. The Cd concentration in the sediments exceeded the US Environmental Protection Agency's Sediment Quality Guideline (SQG) values, and the geoaccumulation index (Igeo) values indicated heavy to extreme pollution. In addition, the Cd, Cu, and Pb concentrations in aquatic plants exceeded the WHO guidelines for these contaminants. Between the fish species, tilapia accumulated significantly higher (P < 0.05) Cu in their organ tissues than carp, confirming the bioaccumulation of some metals in the aquatic fauna. The edible muscles of the fish specimens had metal concentrations below the maximum permissible levels established by statutory guidelines. In addition, a human health risk assessment, performed using the estimated weekly intake (EWI) values, indicated that farmed fish from the Yonki Reservoir are safe for human consumption. PMID- 27663880 TI - Gamma Knife radiosurgery for cervical spine lesions: expanding the indications in the new era of Icon. PMID- 27663881 TI - Does corticosterone mediate predator-induced responses of larval Hylarana indica? AB - Prey-predator interactions have been studied extensively in terms of morphological and behavioural responses of prey to predation risk using diverse model systems. However, the underlying physiological changes associated with morphological, behavioural or life historical responses have been rarely investigated. Herein, we studied the effect of chronic predation risk on larval growth and metamorphosis of Hylarana indica and the underlying physiological changes in prey tadpoles. In the first experiment, tadpoles were exposed to a caged predator from Gosner stage 25-42 to record growth and metamorphosis. Further, whole body corticosterone (CORT) was measured to determine the physiological changes underlying morphological and life historical responses of these prey tadpoles. Surprisingly, tadpoles experiencing continuous predation risk grew and developed faster and metamorphosed at a larger size. Interestingly, these tadpoles had significantly lower CORT levels. In the second experiment, tadpoles were exposed to predation risk (PR) or PR+CORT from stage 25-42 to determine the role of CORT in mediating predator-induced responses of H. indica. Tadpoles facing continuous predation risk grew and developed faster and metamorphosed at a larger size reinforcing the results of the first experiment. However, when CORT was administered along with predation risk, tadpoles grew and developed slowly leading to delayed metamorphosis. Interestingly, growth and metamorphic traits of tadpoles exposed to PR+CORT were comparable to those of the control group indicating that exogenous CORT nullified the positive effect of predation risk. Apparently, CORT mediates predator-induced morphological responses of H. indica tadpoles by regulating their physiology. PMID- 27663882 TI - Prolactin and cortisol regulate branchial claudin expression in Japanese medaka. AB - Several gill claudin (Cldn) tight junction proteins in Japanese medaka are regulated by salinity (cldn10 paralogs and cldn28b), while others are constitutively expressed (cldn27a, cldn28a and cldn30c). The role of the endocrine system in this regulation has yet to be understood. The in vitro effects of cortisol and prolactin on cldn expression in gill explant cultures were investigated in medaka. ncc2b and cftr were used as markers of specific ionocytes associated with freshwater- and seawater-acclimation, respectively. Concentration-response experiments were performed by overnight incubation with 0, 0.1, 1 and 10MUgmL-1 cortisol or 0, 0.01, 0.1 and 1MUgmL-1 ovine prolactin. Cortisol significantly up-regulated cftr, ncc2b, cldn10 paralogs, cldn27a and cldn30c from 1.2- to 5-fold control levels at 10MUgmL-1. Cortisol had no effect on cldn28a and cldn28b. Prolactin had a concentration-dependent effect, decreasing expression of cftr (1MUgmL-1, 2.2-fold) while increasing ncc2b (from 0.1MUgmL-1, 6-7-fold). Prolactin up-regulated expression of 3 cldns: cldn28b (0.1 and 1MUgmL-1), cldn10c and cldn10f (1MUgmL-1), with up to 2-, 2.5- and 2-fold of control level, respectively. A combination experiment with both hormones showed that they act in synergy on cldn28b and have an additive effect on cftr, ncc2b, cldn10c and cldn10f. Our results showed that cortisol and prolactin are essential to maintain the expression of specific branchial claudins. This work also provides evidence that both hormones act directly on gill of medaka to modulate determinants of paracellular ion movement. PMID- 27663883 TI - Neuropeptide Y in the brain of Euphlyctis cyanophlyctis tadpoles responds to hypoxic stress. AB - Neuropeptide Y (NPY) has emerged as a novel peptide to antagonize various physiological consequences of stress within a mammalian brain. Hypoxia induced neuropeptide Y release in mammalian systems is well established. However, the possible role of NPY in regulating the effects of oxygen variation in lower vertebrates has not been investigated. We have studied the distribution and neuro anatomical expression of NPY in the brain of Euphlyctis cyanophlyctis tadpoles, exposed to normal and reduced oxygen levels using immunohistochemistry. Animals exposed to hypoxia (<2mg/ml) exhibited a significant amplification of NPY immunoreactivity throughout the brain. Increased NPY-ir perikarya appeared in all the sub-divisions of pallium, septum and preoptic area of telencephalon; suprachiasmatic nucleus, central and lateral thalamus, infundibulum and habenular regions of diencephalon; and nucleus cerebella and medulla of rhombencephalon. Most of these regions form the stress and anxiety regulating centers of a vertebrate brain and some of the parallel regions also respond to respiratory reflexes in mammals. Hence, our results suggest NPY induced modulation of hypoxia in Euphlyctis cyanophlyctis tadpoles. PMID- 27663884 TI - Clown's view as respicio: looking respectfully to and after people with dementia. AB - Clowns seem suspect when it comes to respect. The combination of clowning and people with dementia may seem especially suspicious. In this argument, I take potential concerns about clowning in dementia care as an opportunity to explore the meaning of a respectful approach of people with dementia. Our word 'respect' is derived from the Latin respicio, meaning 'looking back' or 'seeing again', as well as 'looking after' or 'having regard' for someone or something. I build upon this double meaning of respicio by examining how simultaneously we look to and after people with dementia. I do so empirically by studying how miMakkus clowns in their practice learn to look with new eyes to people and things around them. I call this clown's view and differentiate it from the predominant way of observing people in dementia care. I argue that respicio comes in two guises, each of which merges specific forms of looking to and looking after the other. By making conventional, solidified ways of seeing the other fluid again, clowns remind us of the value that comes with a veiled way of paying respect to people with dementia. PMID- 27663886 TI - High-fat diet-induced downregulation of anorexic leukemia inhibitory factor in the brain stem. AB - OBJECTIVE: High-fat diet (HFD) is known to induce low-grade hypothalamic inflammation. Whether inflammation occurs in other brain areas remains unknown. This study tested the effect of short-term HFD on cytokine gene expression and identified leukemia inhibitory factor (LIF) as a responsive cytokine in the brain stem. Thus, functional and cellular effects of LIF in the brain stem were investigated. METHODS: Male rats were fed chow or HFD for 3 days, and then gene expression was analyzed in different brain regions for IL-1beta, IL-6, TNF-alpha, and LIF. The effect of intracerebroventricular injection of LIF on chow intake and body weight was also tested. Patch clamp recording was performed in the nucleus tractus solitarius (NTS). RESULTS: HFD increased pontine TNF-alpha mRNA while downregulating LIF in all major parts of the brain stem, but not in the hypothalamus or hippocampus. LIF injection into the cerebral aqueduct suppressed food intake without conditioned taste aversion, suggesting that LIF can induce anorexia via lower brain regions without causing malaise. In the NTS, a key brain stem nucleus for food intake regulation, LIF induced acute changes in neuronal excitability. CONCLUSIONS: HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS. PMID- 27663887 TI - Function of membranous lysyl-tRNA synthetase and its implication for tumorigenesis. AB - Aminoacyl-tRNA synthetases (ARSs) are essential enzymes that conjugate specific amino acids to their cognate tRNAs for protein synthesis. Besides their catalytic activity, recent studies have uncovered many additional functions of these enzymes through their interactions with diverse cellular factors. Among human ARSs, cytosolic lysyl-tRNA synthetase (KRS) is often highly expressed in cancer cells and tissues, and facilitates cancer cell migration and invasion through the interaction with the 67kDa laminin receptor on the plasma membrane. Specific modulation of this interaction by small molecule inhibitors has revealed a new way to control metastasis. Here, we summarize the pro-metastatic functions of KRS and their patho-physiological implications. PMID- 27663885 TI - miRNA-429 Inhibits Astrocytoma Proliferation and Invasion by Targeting BMI1. AB - Glioblastoma multiforme (GBM), the most common primary brain cancer in adults, is usually the most lethal type of brain tumor. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that deeply involves with the regulation of gene expression and cellular processes, including proliferation, apoptosis, migration and invasion. The objective of the study is to investigate the effect of miRNA 429 on human glioblastoma tissues and cell lines. miRNA-429 expressions in human glioblastoma, normal brain tissue samples, and human malignant glioma cell lines (U87, U251 and LN229) were compared using reverse transcription-quantitative PCR and western blot methods. U251 cell lines were transfected with miRNA-429 mimics, and then the effects of miRNA-429 on cell proliferation and invasion were investigated by CCK8 and Transwell invasion assay, respectively. It was found that miRNA-429 expression was significantly reduced in the examined Glioblastoma samples and human glioma cell lines. Overexpression of miRNA-429 inhibited Glioblastoma cell proliferation and invasion. Additionally, the present study also showed that BMI1 was a functional target of miRNA-429. Overexpression of BMI1 undermined the inhibition effect of miRNA-429 in glioblastoma and U251 cell lines. The current study demonstrated that miRNA-429, as a tumor suppressor gene, was capable of negatively regulating the expression of BMI1 in U251 cells. PMID- 27663888 TI - Proteomic study of hepatocellular carcinoma using a novel modified aptamer-based array (SOMAscanTM) platform. AB - Vascular invasion is a pathological hallmark of hepatocellular carcinoma (HCC), associated with poor prognosis; it is strongly related to the early recurrence and poor survival after curative resection. In order to determine the proteomic backgrounds of HCC carcinogenesis and vascular invasion, we employed a novel modified aptamer-based array (SOMAscan) platform. SOMAscan is based on the Slow Off-rate Modified Aptamers (SOMAmers), which rely on the natural 3D folding of single-stranded DNA-based protein affinity reagents. Currently, the expression level of 1129 proteins can be assessed quantitatively. Correlation matrix analysis showed that the overall proteomic features captured by SOMAscan differ between tumor and non-tumor tissues. Non-tumor tissues were shown to have more homogeneous proteome backgrounds than tumor tissues. A comparative study identified 68 proteins with differential expression between tumor and non-tumor tissues, together with eight proteins associated with vascular invasion. Gene Ontology analysis showed that the extracellular space and extracellular region proteins were predominantly detected. Network analysis revealed the linkage of seven proteins, AKT1, MDM2, PTEN, FGF1, MAPK8, PRKCB, and FN1, which were categorized as the components of "Pathways in cancer" in pathway analysis. The results of SOMAscan analysis were not concordant with those obtained by western blotting; only the determined FN1 levels were concordant between the two platforms. We demonstrated that the proteome captured by SOMAscan includes the proteins relevant to carcinogenesis and vascular invasion in HCC. The identified proteins may serve as candidates for the future studies of disease mechanisms and clinical applications. PMID- 27663889 TI - What are the structural features that drive partitioning of proteins in aqueous two-phase systems? AB - Protein partitioning in aqueous two-phase systems (ATPSs) represents a convenient, inexpensive, and easy to scale-up protein separation technique. Since partition behavior of a protein dramatically depends on an ATPS composition, it would be highly beneficial to have reliable means for (even qualitative) prediction of partitioning of a target protein under different conditions. Our aim was to understand which structural features of proteins contribute to partitioning of a query protein in a given ATPS. We undertook a systematic empirical analysis of relations between 57 numerical structural descriptors derived from the corresponding amino acid sequences and crystal structures of 10 well-characterized proteins and the partition behavior of these proteins in 29 different ATPSs. This analysis revealed that just a few structural characteristics of proteins can accurately determine behavior of these proteins in a given ATPS. However, partition behavior of proteins in different ATPSs relies on different structural features. In other words, we could not find a unique set of protein structural features derived from their crystal structures that could be used for the description of the protein partition behavior of all proteins in all ATPSs analyzed in this study. We likely need to gain better insight into relationships between protein-solvent interactions and protein structure peculiarities, in particular given limitations of the used here crystal structures, to be able to construct a model that accurately predicts protein partition behavior across all ATPSs. PMID- 27663890 TI - Toxicology of deoxynivalenol and its acetylated and modified forms. AB - Mycotoxins are the most frequently occurring natural contaminants in human and animal diet. Among them, deoxynivalenol (DON), produced by Fusarium, is one of the most prevalent and thus represents an important health risk. Recent detection methods revealed new mycotoxins and new molecules derivated from the "native" mycotoxins. The main derivates of DON are the acetylated forms produced by the fungi (3- and 15-acetyl-DON), the biologically "modified" forms produced by the plant (deoxynivalenol-3-beta-D-glucopyranoside), or after bacteria transformation (de-epoxy DON, 3-epi-DON and 3-keto-DON) as well as the chemically "modified" forms (norDON A-C and DON-sulfonates). High proportions of acetylated and modified forms of DON co-occur with DON, increasing the exposure and the health risk. DON and its acetylated and modified forms are rapidly absorbed following ingestion. At the molecular level, DON binds to the ribosome, induces a ribotoxic stress leading to the activation of MAP kinases, cellular cell-cycle arrest and apoptosis. The toxic effects of DON include emesis and anorexia, alteration of intestinal and immune functions, reduced absorption of the nutrients as well as increased susceptibility to infection and chronic diseases. In contrast to DON, very little information exists concerning the acetylated and modified forms; some can be converted back to DON, their ability to bind to the ribosome and to induce cellular effects varies according to the toxin. Except for the acetylated forms, their toxicity and impact on human and animal health are poorly documented. PMID- 27663891 TI - Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions. AB - Polychlorinated biphenyls (PCBs) contain 209 congeners with various structure activities. Exposure to PCBs was related to disorders of female reproduction. Endometriosis (EM) is an estrogen- and inflammation-dependent disease with high prevalence and severe health outcomes. Epidemiological studies have shown the effects of PCBs exposure on EM in regard to various structures of PCBs. However, little evidence is available from the toxicology considering the structure of PCBs. In the study, environmentally relevant concentrations of PCBs were used to treat primary cultured endometrial cells and an EM mouse model. Dioxin-like CB126, but not non-dioxin-like CB153, significantly enhanced 17beta-estradiol (E2) biosynthesis in a dose-dependent manner. Among the genes related to estrogen metabolism, the level of 17beta-hydroxysteroid dehydrogenase 7 (HSD17B7) showed significant increase following CB126 exposure. We further found that CB126 exposure decreased the methylation of the HSD17B7 promoter. Elevated expression of HSD17B7 was observed in the eutopic endometrium of EM patients. CB126 rather than CB153 triggered the inflammatory response by directly stimulating the secretion of inflammatory factors and indirectly reducing the level of lipoxin A4 (LXA4). Furthermore, the inflammation enhanced the expression of HSD17B7. Antagonism of the aryl hydrocarbon receptor (AhR) diminished the effects induced by CB126. In vivo, the PCB-treated EM mouse model confirmed that CB126 rather than CB153 increased the levels of both E2 and inflammatory factors in peritoneal fluid and promoted the development of endometriotic lesions. In all, CB126, but not CB153, triggered EM development by stimulating estrogen biosynthesis, inflammation and their interactions and that these effects were mediated by the AhR receptor. PMID- 27663892 TI - Role of EhRab7A in phagocytosis of type 1 fimbriated E. coli by Entamoeba histolytica. AB - Entamoeba histolytica, the causative agent of amoebic colitis and liver abscess in human, ingests the intestinal bacteria and variety of host cells. Phagocytosis of bacteria by the amebic trophozoite has been reported to be important for the virulence of the parasite. Here, we set out to characterize different stages of phagocytosis of type 1 E. coli and investigated the role of a set of amoebic Rab GTPases in the process. The localizations of the Rab GTPases during different stages of the phagocytosis were investigated using laser scanning confocal microscopy and their functional relevance were determined using fluorescence activated cell sorter based assay as well as colony forming unit assay. Our results demonstrate that EhRab7A is localized on the phagosomes and involved in both early and late stages of type 1 E. coli phagocytosis. We further showed that the E. coli or RBC containing phagosomes are distinct from the large endocytic vacuoles in the parasite which are exclusively used to transport human holotransferrin and low density lipoprotein. Remarkably, type 1 E. coli uptake was found to be insensitive to cytochalasin D treatment, suggesting that the initial stage of E. coli phagocytosis is independent of the formation of actin filaments. PMID- 27663893 TI - Improved Efficacy of Neoadjuvant Compared to Adjuvant Immunotherapy to Eradicate Metastatic Disease. AB - : Immunotherapy has recently entered a renaissance phase with the approval of multiple agents for the treatment of cancer. Immunotherapy stands ready to join traditional modalities, including surgery, chemotherapy, radiation, and hormone therapy, as a pillar of cancer treatment. Although immunotherapy has begun to have success in advanced cancer treatment, its scheduling and efficacy with surgery to treat earlier stages of cancer and prevent distant metastases have not been systematically examined. Here, we have used two models of spontaneously metastatic breast cancers in mice to illustrate the significantly greater therapeutic power of neoadjuvant, compared with adjuvant, immunotherapies in the context of primary tumor resection. Elevated and sustained peripheral tumor specific immune responses underpinned the outcome, and blood sampling of tumor specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. These data now provide a strong rationale to extensively test and compare neoadjuvant immunotherapy in humans. SIGNIFICANCE: We demonstrate the significantly greater therapeutic efficacy of neoadjuvant, compared with adjuvant, immunotherapies to eradicate distant metastases following primary tumor resection. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood sampling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. Cancer Discov; 6(12); 1382-99. (c)2016 AACR.See related commentary by Melero et al., p. 1312This article is highlighted in the In This Issue feature, p. 1293. PMID- 27663900 TI - Measuring a hidden population: A novel technique to estimate the population size of women with sexual violence-related pregnancies in South Kivu Province, Democratic Republic of Congo. AB - Successive sampling (SS)-population size estimation (PSE) is a technique used to estimate the sizes of hidden populations using data collected in respondent driven sampling (RDS) surveys. We assess past estimations and use new data from an RDS survey to calculate a new PSE. In 2012, 852 adult women in South Kivu Province, Democratic Republic of Congo, who self-identified as survivors of sexual violence, resulting in a pregnancy, since the start of the war (in 1996) were sampled using RDS. We used imputed visibility, enrollment order, and prior estimates for PSE using SS-PSE in RDS Analyst. Prior estimates varied between Congolese local experts and researchers. We calculated the PSE of women with a sexual violence-related pregnancy in South Kivu using researchers' priors to be approximately 17,400. SS-PSE is an effective method for estimating the population sizes of hidden populations, useful for providing evidence for services and resource allocation. SS-PSE is beneficial because population sizes can be calculated after conducting the survey and do not rely on separate studies or additional data (as in network scale-up, multiplier, and capture-recapture methods). PMID- 27663899 TI - Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance. AB - : Lung squamous cell carcinoma (LSCC) pathogenesis remains incompletely understood, and biomarkers predicting treatment response remain lacking. Here, we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histologic and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in patients with non-small lung cancer (NSCLC) and could be noninvasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. SIGNIFICANCE: We developed an LSCC mouse model involving Trp53 and Keap1, which are frequently mutated in human LSCCs. In this model, ABSCs are the cell of origin of these tumors. KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy patients. Our findings are of potential clinical relevance and could lead to personalized treatment strategies for tumors with KEAP1/NRF2 mutations. Cancer Discov; 7(1); 86-101. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 1. PMID- 27663902 TI - Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. AB - Bempedoic acid (ETC-1002), a novel therapeutic approach for low-density lipoprotein cholesterol (LDL-C) lowering, inhibits ATP citrate lyase (ACL), an enzyme involved in fatty acid and cholesterol synthesis. Although rodent studies suggested potential effects of ACL inhibition on both fatty acid and cholesterol synthesis, studies in humans show an effect only on cholesterol synthesis. In phase 2 studies, ETC-1002 reduced LDL-C as monotherapy, combined with ezetimibe, and added to statin therapy, with LDL-C lowering most pronounced when ETC-1002 was combined with ezetimibe in patients who cannot tolerate statins. Whether clinically relevant favorable effects on other cardiometabolic risk factors such as hyperglycemia and insulin resistance occur in humans is unknown and requires further investigation. Promising phase 2 results have led to the design of a large phase 3 program to gain more information on efficacy and safety of ETC-1002 in combination with statins and when added to ezetimibe in statin-intolerant patients. PMID- 27663901 TI - Open Versus Endovascular or Hybrid Thoracic Aortic Aneurysm Repair. AB - Thoracic aortic aneurysms are associated with significant morbidity and mortality. There are multiple underlying etiologies, including genetic abnormalities, that have important implications in their natural history. The variable histologic, anatomic, and clinical presentations necessitate careful consideration of available treatment options. Surgical repair of these aneurysms has been the mainstay of treatment; however, these approaches can carry a relatively high risk of morbidity and mortality. Endovascular approaches have now become first-line therapy for descending thoracic aneurysms, and with advancements in graft technology, endovascular approaches are being increasingly employed for hybrid repairs of the aortic arch and even the ascending aorta. However, to date, clinical outcomes from randomized trials and long-term follow up are limited. As technology continues to advance, there is the potential for further integration of surgical and endovascular treatments so that patients have the best opportunity for a favorable outcome. PMID- 27663904 TI - An agenda for knowledge-oriented research on bilingualism in children with developmental disorders. PMID- 27663903 TI - Mindful creativity matters: trajectories of reported functioning after severe traumatic brain injury as a function of mindful creativity in patients' relatives: a multilevel analysis. AB - OBJECTIVE: The objective of the present investigation was to examine the association of mindful creativity with the trajectory of recovery (emotional, interpersonal, cognitive, and total functioning) of patients with severe TBI. METHODS: This was drawn from a subsample of an adult prospective cohort study on severe TBI in Switzerland; patients and their relatives were assessed at 3, 6, and 12 months (patients N = 176, relatives N = 176). Predictor measures were assessed using Mindful Creativity Scale-short form and time (trajectory of functioning of the patient over time). Outcome measures were assessed using Patient Competency Rating Scale for Neuro-rehabilitation (PCRS-NR; measuring emotional, interpersonal, cognitive, and total functioning post-injury). All measures were assessed at each time point. Mixed linear models were run separately for ages >50 and <=50 (i.e., bimodal distribution). RESULTS: Patients' mindful creativity showed no significant association with patients' functioning across time in any of the models. In all age groups, interpersonal functioning decreased across time (slope>50 = -4.66, p = .037; slope<=50 = -7.19, p = .007). Interestingly, in age group <=50, interpersonal functioning increased when looking at relative mindful creativity by time (slope = 1.69, p = .005). Additionally, relatives mindful creativity was significantly associated with patients' functioning in age group <=50: (a) patients' total functioning (slope = 0.18, p = .03) and (b) cognitive functioning (slope = 0.72, p = .020). CONCLUSIONS: Relatives' mindful creativity was significantly associated with patients' functioning after severe TBI. Implications for treatment and future research are discussed. PMID- 27663905 TI - Matrix metalloproteinase-8 activity in gingival crevicular fluid: development of a novel assay. AB - BACKGROUND AND OBJECTIVE: The matrix metalloproteinases (MMPs) play a role in regulating turnover and metabolism of connective tissues in health but they have also been implicated in a wide variety of pathological conditions, including periodontal disease. MMP-8 has been extensively studied in periodontal health and disease using ELISA, although this technique is limited by its inability to determine enzyme activity. The aim was to develop an assay specifically to measure MMP-8 activity and to demonstrate its use in the analysis of gingival crevicular fluid samples. MATERIAL AND METHODS: A specific antibody was used to coat black 96-well microtitre plates to capture MMP-8 selectively. The activity of bound MMP-8 was measured using a fluorogenic substrate. Gingival crevicular fluid samples, from healthy and periodontally diseased sites, were collected using PerioPaper strips and tested for MMP-8 activity. RESULTS: Significantly higher MMP-8 activity was demonstrated in gingival crevicular fluid from periodontally diseased sites compared with healthy sites that exhibited basal or no MMP-8 activity. No cross-reactivity with other MMPs was noted. CONCLUSION: We show, for the first time, that MMP-8 activity can be specifically detected and quantified in gingival crevicular fluid samples. Measurement of MMP-8 activity could prove to be useful in monitoring periodontal disease progression. PMID- 27663906 TI - Fungal infections of the lung in children. AB - Fungal infections of the lungs are relatively common and potentially life threatening conditions in immunocompromised children. The role of imaging in children with lung mycosis is to delineate the extension of pulmonary involvement, to assess response to therapy, and to monitor for adverse sequelae such as bronchiectasis and cavitation. The aim of this paper is to show imaging findings in a series of patients with fungal pneumonia from two tertiary children's hospitals, to discuss differential diagnoses and to show how imaging findings can vary depending on the host immune response. PMID- 27663907 TI - Horseradish peroxidase-assisted approach to decolorize and detoxify dye pollutants in a packed bed bioreactor. AB - In this study, horseradish peroxidase (HRP) was covalently immobilized on the calcium-alginate support using glutaraldehyde (GA) as a cross-linking reagent for detoxification and degradation of synthetic dyes. Immobilization procedure furnished significant immobilization efficiency (86.27 +/- 3.43%) along with apparent and relative activity of 24.39 +/- 1.03 U/g and 84.97 +/- 3.54%, respectively, for immobilized-HRP. In comparison to free-state, immobilized-HRP catalyzed the substrate oxidation reaction in a slightly acidic and wider temperature range, with an optimum at 60 degrees C. After 10 and 60 min of incubation at 60 degrees C, the immobilized-HRP displayed 99.0% and 89.0% of residual activities, whereas the free counterpart retained only 34.0% and 18.0% of residual activities, respectively. Moreover, the immobilized-HRP showed potential efficiency for the decolorization of dyes in sequential dye decolorizing batch reactions. Cytotoxicity analysis using a plant bioassay and acute test demonstrated that the Ca-alginate immobilized-HRP may effectively be used for detoxification of dyes and has a great potential for large-scale environmental remediation. PMID- 27663908 TI - Hitting is male, giving is female: automatic imitation and complementarity during action observation. AB - Is somebody going to hurt us? We draw back. The present study investigates using behavioral measures the interplay between imitative and complementary actions activated while observing female/male hands performing different actions. Female and male participants were required to discriminate the gender of biologically and artificially colored hands that displayed both individual (grasping) and social (giving and punching) actions. Biological hands evoked automatic imitation, while hands of different gender activated complementary mechanisms. Furthermore, responses reflected gender stereotypes: giving actions were more associated to females, punching actions to males. Results have implications for studies on social stereotyping, and for research on action observation, showing that the mirror neuron system resonates in both an imitative and complementary fashion. PMID- 27663909 TI - Epidemiology, microbiology, clinical characteristics, and outcomes of candidemia in internal medicine wards-a retrospective study. AB - BACKGROUND: The clinical characteristics of internal medicine ward (IMW) patients with candidemia are unclear. The aim of this study was to define the clinical characteristics of candidemic IMW patients and to study the incidence, species distribution, and outcomes of these patients compared to surgical and intensive care unit (ICU) candidemic patients. METHODS: A retrospective cohort of candidemic patients in IMWs, general surgery wards, and an ICU at Beilinson Hospital during the period 2007-2014 was analyzed. RESULTS: A total of 118 patients with candidemia were identified in six IMWs, two general surgery wards, and one ICU in the hospital. Candida albicans was the leading causative agent (41.1%). Higher proportions of Candida parapsilosis and Candida tropicalis isolates were observed in the IMW patients. IMW patients were significantly older, with poorer functional capacity, and had more frequently been exposed to antibiotic therapy within 90 days, in particular beta-lactam-beta-lactamase inhibitor combinations and cephalosporins. At onset of candidemia, a significantly lower number of IMW patients were mechanically ventilated (p<0.01); these patients did not have central line catheters comparable to ICU and surgical patients (p<0.001). They were less likely to receive adequate antifungal therapy within 48h, and this was the only significant predictor of survival in these patients (p=0.028): hazard ratio 3.7 (95% confidence interval 1.14-12.5) for therapy delayed to >48h. CONCLUSIONS: IMW candidemic patients account for a substantial proportion of candidemia cases and have unique characteristics and high mortality rates. PMID- 27663911 TI - Characteristics of retractions related to faked peer reviews: an overview. AB - A faked peer review is a novel cause for retraction. We reviewed the characteristics of papers retracted due to a faked peer review. All papers retracted due to faked peer reviews were identified by searching the Retraction Watch website and by conducting a manual search. All identified papers were confirmed in published journals. The information of retracted papers was collected, which primarily included publisher, journal, journal impact factor, country, as well as publication and retraction year. Overall, 250 retracted papers were identified. They were published in 48 journals by six publishers. The top 5 journals included the Journal of Vibration and Control (24.8%), Molecular Biology Reports (11.6%), Immunopharmacology and Immunotoxicology (8.0%), Tumour Biology (6.8%) and European Journal of Medical Research (6.4%). The publishers included SAGE (31%), Springer (26%), BioMed Central (18%), Elsevier (13%), Informa (11%) and LWW (1%). A minority (4%) of retracted papers were published in Science Citation Index (SCI) journals with an impact factor of >5. A majority (74.8%) of retracted papers were written by Chinese researchers. In terms of the publication year, the retracted papers were published since 2010, and the number of retracted papers peaked in 2014 (40.8%). In terms of the retraction year, the retractions started in 2012, and the number of retractions peaked in 2015 (59.6%). The number of papers retracted due to faked peer reviews differs largely among journals and countries. With the improvement of the peer review mechanism and increased education about publishing ethics, such academic misconduct may gradually disappear in future. PMID- 27663912 TI - [How I do... laparoscopic segmentary ureterectomy]. PMID- 27663910 TI - Wide spread of OXA-23-producing carbapenem-resistant Acinetobacter baumannii belonging to clonal complex II in different hospitals in Lebanon. AB - OBJECTIVES: To investigate the molecular epidemiology of Acinetobacter baumannii strains isolated from different hospitals in Lebanon. METHODS: A total of 119 non duplicate Acinetobacter strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and partial rpoB gene sequencing. Antibiotic susceptibility testing was performed by disc diffusion method and all identified carbapenem-resistant isolates were investigated by PCR assays for the presence of the carbapenemase-encoding genes. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used for molecular typing. RESULTS: Of the 119 A. baumannii isolates, 76.5% were resistant to carbapenems. The most common carbapenemase was the OXA-23-type, found in 82 isolates. The study of population structure using MLST revealed the presence of 30 sequence types (STs) including 18 new ones, with ST2 being the most commonly detected, accounting for 61% of the isolates typed. PFGE performed on all strains of ST2 identified a major cluster of 53 isolates, in addition to three other minor clusters and ten unique profiles. CONCLUSIONS: This study highlights the wide dissemination of highly related OXA-23-producing carbapenem resistant A. baumannii belonging to the international clone II in Lebanon. Thus, appropriate infection control measures are recommended in order to control the geographical spread of this clone in this country. PMID- 27663913 TI - [Simulation' benefits in obstetrical emergency: Which proof level?] AB - Simulation in obstetrical emergency is in expansion. The important economic and human cost in simulation needs a real evaluation about enhancement in technical and non-technical skills, maternal and neonatal morbidity and mortality. We present a literature review of the results published on the subject in shoulder dystocia, post-partum haemorrhage, eclampsia and cord prolaps with a selection of publications with high evidence level or positive impact of training on obstetrical emergencies. There are few publications with a positive impact of training on obstetrical emergencies. Some publications from 10years by the same obstetrical team for training and shoulder dystocia reveal a 75% reduction in brachial plexus injury after 4years of training, and 100% reduction in permanent injury after a decade of training. Only one publication is in accordance with a reduction of severe post-partum haemorrhage with training. For all obstetrical emergencies, crew resource management (communication, self-confidence...) and team training are improved. PMID- 27663914 TI - [Controversies in tubal sterilization]. PMID- 27663916 TI - Psoriasis Induced by Anti-Tumor Necrosis Factor Alpha Agents: A Comprehensive Review of the Literature. AB - Tumor necrosis factor alpha (TNF-alpha) inhibitors revolutionized the management of patients affected by autoimmune diseases such as inflammatory bowel diseases, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. The biologic agents targeted to block TNF-alpha such as infliximab, adalimumab, certulizumab pegol, etanercept, and golimumab, have a good safety profile; however, with increasing, broader, and prolonged use, patients could be exposed to an increased risk of adverse reactions including a wide spectrum of dermatological conditions of different etiology and morphology. Among these, of particular interest is the development of skin immune-mediated diseases that seem to be the consequence of the paradoxical inflammation induced by anti-TNF-alpha therapy. The majority of these lesions are identified as psoriasiform with three main morphologies and different frequency: pustular psoriasis, signs of psoriasis, and guttate; although erythrodermic or inverted psoriasis, among others, may be observed with less frequency. The increased incidence of these dermatological immune-mediated lesions highlight the importance of the skin as a main target of the side effect of anti-TNF-alpha agents, while the immunopathogenetic hypothesis of these paradoxical effects are quite intriguing. The aim of this review is to collect and to analyze existing knowledge to better understand the pathogenetic mechanism of these complications and suggest new fields of investigation, improve therapeutic strategies of autoimmune diseases, and prevent and/or better address such complications. PMID- 27663915 TI - Underlying Mechanisms that Restore Spermatogenesis on Transplanting Healthy Niche Cells in Busulphan Treated Mouse Testis. AB - Very small embryonic-like stem cells (VSELs) exist among spermatogonial stem cells and survive chemotherapy in both mice and human testes because of their relatively quiescent nature. Our earlier study revealed that inter-tubular transplantation of niche (Sertoli or bone marrow derived mesenchymal) cells can restore spermatogenesis from endogenous surviving VSELs. Present study was undertaken to delineate the effect of busulphan on testicular stem/germ/Sertoli cells and to comprehend the underlying mechanisms of how transplanted niche cells restore spermatogenesis. Ploidy analysis showed an increase in diploid cells on D7 and VSELs (2-6 MUm; LIN-/CD45-/SCA-1+) were detected at all time-points studied and were maximum on D15 after busulphan treatment. They were visualized in cell smears, expressed nuclear NANOG and SOX2 and BrdU uptake on D15 suggested they were proliferating in response to stress induced by busulphan. Verapamil sensitive side population detected comprised SCA-1 positive stem cells (5 +/- 0.02 % in normal and 8.6 +/- 2.02 % in chemoablated testis). Adverse effects of busulphan on Sertoli cells by transcriptome analysis included altered expression of Gdnf, Scf, Fgf, Bmp4, androgen binding protein, components of blood-testis barrier and also stem cells related signaling pathways including Wnt. GFP positive transplanted cells aligned themselves as 'neo-tubules' and were visualized adjacent to 'native' germ cells depleted tubules. 'Neo-tubules' provide paracrine support to endogenous VSELs to undergo spermatogenesis. Quantitative analysis was done to track proliferation (PCNA) and differentiation (MVH) of stem cells by immuno-localization studies at different time intervals. Results provide an alternative strategy to restore spermatogenesis in cancer survivors from endogenous stem cells which needs to be further researched. PMID- 27663917 TI - Treatment Options for Pediatric Psoriasis. AB - Psoriasis is a multifactorial inflammatory papulosquamous disease affecting 0.5% to 2% of the pediatric population. Pediatric psoriasis, presenting similar to adult psoriasis, significantly reduces patient quality of life, often requiring an individualized treatment approach for each patient. Combination and rotational therapy are helpful in reducing toxicity and maximizing efficacy. Patients with mild and limited disease severity respond well to topical treatment with steroids or vitamin D analogues, unlike moderate and severe psoriasis where sufficient remission is rarely achieved. Therefore phototherapy, systemic immunomodulators, or biologic agents are the next line of treatment to be considered. There is limited data available on the use and long-term safety of biologics in the pediatric population. Biologic agents must be administered by experienced dermatologists, only in patients with moderate-to-severe plaque psoriasis who are intolerant or refractory to other systemic conventional disease-modifying treatment or phototherapy, or if those treatments are contraindicated. PMID- 27663919 TI - Cardiovascular Comorbidities in Patients with Psoriasis: Risk Profile Including Carotide Ultrasonography Assessed in Hospital-based Case Control Study. AB - Psoriasis is a chronic inflammatory disease, and its comorbidities have attracted serious interest in recent years. The evidence that psoriasis is associated with systemic inflammation and significantly higher incidence of cardiovascular risk factors has already been described. The results of published studies are highly variable, the conclusions are ambiguous, and further epidemiological studies are needed for validation of published data. Therefore, we initiated a project aimed at identifying the association with cardiovascular risk factors, including early stages of atherosclerosis, that represent important comorbidities in patients with psoriasis. We carried out a hospital-based case-control study on 189 patients with chronic plaque psoriasis enrolled as cases. The control group consisted of 378 patients with other skin diseases complying with the same exclusion criteria who were recruited to the study as the controls. All participants underwent physical examination, blood tests, and measuring of blood pressure and waist circumference. Furthermore, we evaluated carotid intima-media thickness (CIMT) in a subset of 117 cases and controls (matched 1:2) with no history of cardiovascular disease. The results showed higher prevalence of hypertension, hyperlipidemia, waist circumference, weight, body-mass index (BMI), and C-reactive protein (CRP) level in patients with psoriasis than in controls. These parameters have been clearly demonstrated to be risk factors for the development of cardiovascular diseases. The associations between psoriasis and diastolic blood pressure, BMI value, and low-density lipoprotein (LDL) cholesterol were statistically significant in the binary data logistic model as well. CIMT was not significantly higher in patients compared with controls. PMID- 27663918 TI - Cardiovascular Risk Evaluation through Heart Rate Variability (HRV) Analysis in Patients with Psoriasis before and after 12 Weeks of Etanercept Therapy: A Preliminary Prospective Study. AB - The association between psoriasis and cardiovascular diseases has been indicated by epidemiological studies. The sub-inflammatory systemic state that characterizes both psoriasis and atherosclerosis has been proposed as the link between these conditions; it cannot, however, explain the increased incidence of sudden cardiac death reported in young patients with severe psoriasis without common cardiovascular risk factors. In a previous study, we reported higher levels of autonomic dysregulation in patients with psoriasis, concluding that the prevalence of the sympathetic arm over the parasympathetic could increase cardiovascular risk. Objective of this study was to assess the influence of etanercept on autonomic cardiovascular regulation in young patients with moderate to-severe psoriasis without cardiovascular risk factors. Five-minute ECG recordings were collected at rest before and after 12 weeks of therapy with etanercept in 19 young patients with psoriasis without cardiovascular risk factors. The Cardiolab CE pocket PC ECG system was used for linear methods of heart rate variability (HRV) analysis. No significant change in HRV analysis parameters was apparent after 12 weeks of etanercept therapy. Our data suggest that treatment with etanercept in patients with moderate-to-severe psoriasis does not affect cardiovascular autonomic regulation and cardiovascular risk. PMID- 27663920 TI - Human Papillomavirus (HPV) Infection and HPV Vaccination: Assessing the Level of Knowledge among Students of the University of Medicine and Pharmacy of Tirgu Mures, Romania. AB - Human papillomavirus (HPV) infection, a causative factor for cervical cancer, remains a topic of great interest. About 80% of sexually active women are at risk of acquiring an HPV infection at some point in life, the peak incidence of infection having been identified in young women. The aim of the study was to assess the knowledge and attitudes of medical students about sexually transmitted diseases, HPV infection, HPV vaccinations, and student sexual behavior. A transversal study was conducted using a questionnaire on students on the 1st and 6th year at the Faculty of Medicine of Tirgu Mures University, Romania. The study resulted in 522 fully completed questionnaires. The percentage of students who had heard about HPV was 82.1% in the 1st year and 99.1% in the 6th year of medical school, but the level of knowledge was different: 62% of senior students had a good or very good level of knowledge, whereas 55.1% of first year students had little knowledge on the topic. About 75% of 6th year students would vaccinate their child against HPV, compared with only 52.4% of 1st year students (P<0.001). The level of knowledge about HPV infection among students in their first year of medical school is rather low, significantly lower compared to 6th year students, which suggests acquiring some basic information in this area since the first year of college or even high school. PMID- 27663921 TI - Dermoscopy of Nodular Melanoma: Review of the Literature and Report of 3 Cases. AB - Nodular melanoma is the most aggressive subtype of melanoma, with rapid growth rate and metastatic potential. It is usually diagnosed at a locally advanced stage (Breslow thickness <2 mm) and is therefore associated with a poor prognosis. Nodular melanoma often does not fit the classic clinical ABCD criteria, but rather the EFG rule or 3 Cs criteria. Missing the diagnosis of nodular melanoma is a dermatologist's worst nightmare, especially since nodular melanomas can have a non-alarming clinical appearance and imitate a wide range of benign lesions. All evolving nodular lesions, despite their size, symmetry, and color, which cannot be confidently diagnosed as benign, should be excised in order to rule out nodular melanoma. Almost all melanoma-specific dermoscopic criteria are described in context of superficial spreading melanoma. Thus, physicians are not familiar and aware enough of dermoscopic features for early detection of nodular melanomas. Herein we present 3 cases of nodular melanomas from our Department and give a review of the current literature. PMID- 27663922 TI - Prevalence of Candida Species in Patients with Psoriasis. AB - Investigation of Candida yeast prevalence in patients with psoriasis has been performed with the aim of determining their possible role as a trigger factor in the pathogenic process of this disease. The purpose of our study was to investigate the prevalence of Candida species on the skin of intertriginous areas and psoriasis lesions as well as the prevalence of Candida species in the stool of patients with psoriasis. This study also examines a possible correlation between the severity of psoriasis and prevalence of isolated Candida species. The patients with psoriasis were divided into two groups according to the clinical type of psoriasis; a group with plaque psoriasis (PP) and psoriasis inversa (PI) (G1) and a group with psoriasis erythrodermica (PE) and psoriasis pustulosa (PPS) (G2). The group of patients with PP and PI (G1) was divided according to score on the Psoriasis Area Severity Index test (PASI) according to severity of disease into the clinical subgroup with PASI <50 and another subgroup with PASI >50. Mycological analysis of skin samples in patients of the clinical group with PP and PI showed a statistically significant difference as well as correlation between the results of isolated specimens of Candida species from the skin of intertriginous areas and psoriasis lesions, the clinical form of psoriasis, and the PASI score. PMID- 27663923 TI - PUVA-induced Bullous Pemphigoid in Psoriasis. AB - The association between psoriasis vulgaris and bullous pemphigoid is due to the still unclear autoimmune process. The common disease site is the dermo-epidermal junction or basal membrane zone (BMZ), with specific alterations for both diseases. Photochemotherapy (PUVA) is one of the therapeutic modalities for psoriasis and can trigger production of autoantibodies against antigens in the BMZ in patients with subclinical bullous pemphigoid. Furthermore, PUVA therapy can alter the immunological milieu and hence can contribute to the expression of bullous pemphigoid in patients with psoriasis. We observed a bullous eruption compatible with bullous pemphigoid in a psoriatic patient treated with PUVA. We speculate that the cumulative dose of PUVA sufficient for triggering blister formation is individually determined. PMID- 27663924 TI - Mycosis Fungoides Associated with Kaposi's Sarcoma, T-cell Rich B-cell Lymphoma, and T-cell Lymphoma with Angioimmunoblastic Features. AB - A patient with mycosis fungoides (MF), Kaposi's sarcoma, T-cell rich B-cell lymphoma, and T-cell lymphoma with angioimmunoblastic features is described. The appearance of multiple malignancies in this patient may have been caused by previous exposure to radiation in the Chernobyl accident and/or systemic chemotherapy for the initial T-cell rich B-cell lymphoma which he underwent. PMID- 27663925 TI - Acupuncture as a Complementary Method of Traditional Psoriasis Treatment: Myth or Reality? AB - Dear Editor, the practitioners of traditional Chinese medicine described psoriasis some 2000 years ago (1). Psoriasis vulgaris is a common, chronic inflammatory skin disease whose worldwide prevalence ranges from 0.1-3% (2,3). Understanding the role of the immune system in psoriasis and the interplay between the innate and adaptive immune system has helped to manage this complex disease, which affects patients far beyond the skin changes themselves (2). In addition to the usual and widely accepted methods of treatment of psoriasis, including topical therapies, phototherapy, and conventional and biological systemic therapies, data can be found in the literature that suggest a favorable effect of acupuncture on the course of psoriasis (4,5). Despite that, this complementary method of traditional treatment of various diseases is not yet widely accepted worldwide. According to the World Health Organization (WHO), acupuncture has been an officially recognized method of treatment for more than 50 diseases from 1979 (5). At the Department of Neurology at the University Hospital Center Zagreb, acupuncture has been used since 2011 for the treatment of various types of headaches, trigeminal neuralgia, and spinal pain syndromes. We report the case of a patient with a known history of psoriasis who was treated for chronic migraines with acupuncture. The 49-year-old female patient was examined for headache of a pulsating character that she had had for 16 years. The headache was mainly located on the left side of head and accompanied by nausea, vomiting, and both photophobia and phonophobia, and there was a worsening of symptoms upon exertion. The headaches were occurring once a week with an average duration of 2-3 continuous days. The patient also had frequent mild headaches. Additionally, the patient was diagnosed with psoriasis at the age of 29 and was occasionally treated with phototherapy. Systemic therapy for psoriasis had not been given to the patient thus far. After the clinical evaluation and considering the medical history and clinical findings, the diagnosis of chronic migraine was established and prophylactic therapy with dual antidepressant was introduced. On follow-up examinations, a reduction in the frequency and intensity of migraine headaches was observed. After one year there was a progression of symptoms, and treatments with acupuncture were started. Stainless steel filiform needles of 25 mm in length were inserted perpendicularly into points on the head, arm, and legs and retained for 30 minutes. The treatment was administered once a day for 10 days with an interval of 2-3 days between treatments. The patient showed significant improvement for a period of 6 months after the acupuncture treatment, which is why the treatment with acupuncture was repeated. The patient stated that very soon after the beginning of each acupuncture treatment, she had noticed a significant improvement regarding psoriatic lesions as a "side effect". On the first day of acupuncture, extensive erythematosquamous plaques were noticed on the skin of the dorsum of the feet (Figure 1), palms, and elbows. It is important to emphasize that the patient did not use any specific topical antipsoriatic therapies during the acupuncture treatment, but only bland emollients. During the third week of treatment, a significant improvement was observed, or according to the patient, "she has not had such a good skin for a long time" (Figure 2). The improvement of the clinical status can be explained by overlapping acupuncture points used in the treatment of pain syndromes and psoriasis or to the holistic effect of acupuncture. In recent years, several high-quality evidence-based Western medicine guidelines have been developed for the treatment of psoriasis (6,7). In addition to that modern approach, several studies confirmed the effectiveness of acupuncture in the treatment of psoriasis. The recent review by Coyle et al. (4) indicates promising evidence of the efficacy of acupuncture for psoriasis treatment with an increasing number of people achieving clinical and statistical improvements. Furthermore, Wang et al. (8) have recently published the protocol for a systematic review which aims to assess the effectiveness and safety of acupuncture for patients with psoriasis. In acupuncture, hair-thin needles are inserted into the skin, releasing natural pain killers such as adenosine, endorphins, and serotonin into the body. It is known that patients with psoriatic arthritis can benefit from the treatment. Some patients may be concerned that acupuncture needles could worsen a skin flare-up but an acupuncturist uses sterile needles to prevent any risk to flaring skin. The advantage of acupuncture is that it is a very safe alternative medicine treatment and is not likely to interfere with any existing psoriasis treatment. It is important to note that acupuncture is a 5000-year-old alternative medicine treatment and that it has been officially recognized by the WHO for more than three decades (5). After achieving clinical improvement and regression of psoriatic plaques during the acupuncture for headache, the authors reviewed the literature and found reports about possible benefits of treating psoriasis with acupuncture. Therefore, the purpose of this letter and case study is to raise awareness and inform dermatologists about the different and until now under explored possibilities of acupuncture in treating psoriasis. PMID- 27663926 TI - Tinea on a Tattoo. AB - In the last twenty years, the prevalence of individuals with tattoos in the general population has increased in Europe (1) as well as in Australia (2) and the United States of America (3). A series of complications such as acute inflammatory reactions, allergic contact dermatitis (4,5), photoinduced, lichenoid, and granulomatous reactions (6, 7), pseudolymphoma (8), pseudoepitheliomatous hyperplasia (9), skin infections (6), and skin cancers (10) may occur on tattoos. Infectious complications on tattoos include bacterial infections (pyoderma, leprosy, syphilis, cutaneous tuberculosis, mycobacteriosis) (11-14), viral infections (molluscum contagiosum, warts, herpes simplex, hepatitis B and C) (15-17), and fungal infections (sporotrichosis, dermatophytosis) (18,19). We present the case of a 29-year-old immunocompetent female patient who was consulted for the development of an erythematous-squamous placard that appeared on a tattoo about 18 days after tattooing. Dermatological examination revealed a circular, erythematous, scaly plaque, with centrifugal growth and central resolution, presenting an active, raised, erythematous, vesiculopustular edge, giving the appearance of tinea corporis. The lesion's starting point was on the tattoo in two colors located on the middle third of the left calf and subsequently evolved to beyond the surface of tattoo (Figure 1). No other skin, scalp, or nail lesions were observed. Mycological examination of the material obtained by scraping of the scales and the vesicles from the edges and the surface of the plaque revealed numerous hyphae on direct microscopy examination, and white, flat colonies with a cottony surface and radial grooves developed in Sabouraud dextrose agar culture (Figure 2). Spindle-shaped, thick walled macroconidia and a few pyriform microconidia were observed on microscopic examinations of the colonies. Based on macroscopic and microscopic characteristics, Microsporum canis was identified. Gram stain and bacterial culture results were negative. Patient history revealed the presence of a pet dog that was diagnosed with mycosis, the etiologic agent being M. canis. After 21 days of treatment with oral terbinafine (250 mg/day) and topical application of terbinafine 1% cream once a day, the lesion disappeared and mycological examination (direct microscopy and culture) was negative. In the case of tattoos, cutaneous inoculation of a dermatophyte may occur after 1-3 weeks of tattooing, corresponding to the healing phase of the tattoo application. Dermatophyte inoculation can be done by direct contact with an infected person or animal or, exceptionally, by telluric contamination. Despite the increasing number of tattooed people, there are only a few published cases of dermatophytosis arising on tattoos (19,20). Ammirati reported dermatophyte infection caused by Trichophyton tonsurans that occurred two weeks after tattooing, clinically presenting as concentric annular lesions with active vesiculopustular edges which progressively included the entire tattoo (19). Similarly, in our case the infection with M. canis occurred during the healing phase, the dermatophyte lesion occurring after 18 days from tattoo application by direct contact with the dog parasitized with M. canis. In conclusion, dermatophyte infection of tattoos remains possible, although rare. PMID- 27663927 TI - Paid and Unpaid Online Recruitment for Health Interventions in Young Adults. AB - PURPOSE: There is a growing need to identify new and innovative approaches to recruit representative samples of young adults in health intervention research. The current study used a data set of screening information from an online well being intervention trial of young adults, to investigate cost-effectiveness of different recruitment strategies and whether the clinical and demographic characteristics of participants differed depending on paid or unpaid online recruitment sources. METHODS: Data were collected from 334 18- to 25-year-old Australians. The study was advertised through a variety of paid and unpaid online recruitment channels (e.g., Google, Facebook, Twitter, YouTube, recruitment agency), with response rates to different recruitment channels tracked using unique Web links. Well-being of participants was measured using the Mental Health Continuum Short Form. Analyses consisted of independent t tests and chi2 tests. RESULTS: Overall, unpaid recruitment channels had a considerably higher yield than paid recruitment channels. Of paid recruitment channels, a recruitment agency and paid Facebook advertisements attracted the largest number of individuals. This study also found differences between paid and unpaid online recruitment channels with regard to the well-being and mood of participants. CONCLUSIONS: Although the success of online recruitment channels is likely subject to a complex interplay between the number of exposures, the targeted sample, the wording, and placement of the advertisement, as well as study characteristics, our study demonstrated that unpaid recruitment channels are more effective than paid channels and that paid and unpaid channels may result in samples with different characteristics. PMID- 27663928 TI - Rural Inequalities in the Australian Burden of Ischaemic Heart Disease: A Systematic Review. AB - OBJECTIVE: To summarise all available evidence on the differences in burden of ischaemic heart disease (IHD) between metropolitan and rural communities of Australia. METHODS: Systematic review of peer-reviewed literature published between 1990 and 2014. Search terms were derived from the four major topics: (1) rural; (2) ischaemic heart disease; (3) Australia; and (4) burden of disease. Terms were adapted for six databases and two independent researchers screened results. Studies were included if they compared outcomes related to IHD in adults aged 18 years and over, between (at least) two areas of differing remoteness, at the same point in time. RESULTS: Twenty studies were included and presented data collected between 1969 and 2010. Seventeen studies showed a clear disparity in IHD outcomes between major cities and regional and remote areas, with a consistently higher burden observed outside major cities. Among Aboriginal and Torres Strait Islander populations, fewer differences were observed and some IHD outcomes were not associated with remoteness. CONCLUSIONS: Populations outside of major cities in Australia bear a disproportionately high burden of ill health due to IHD, yet the majority of the rural populations are yet to be investigated in terms of burden of disease outcomes from IHD. IMPLICATIONS: Remoteness is a key determinant of IHD burden in Australia. The reasons for increased IHD burden in rural compared to metropolitan communities of Australia are poorly understood, which has implications for the design of targeted interventions to reduce geographical inequalities. PMID- 27663929 TI - An institutional study of time delays for symptomatic carotid endarterectomy. AB - OBJECTIVE: The aim of this study was to assess time delays between first cerebrovascular symptoms and carotid endarterectomy (CEA) at a single center and to systematically evaluate causes of these delays. METHODS: Consecutive adult patients who underwent CEAs between January 2010 and September 2011 at a single university-affiliated center (Centre Hospitalier de l'Universite Montreal-Hotel Dieu Hospital, Montreal) were identified from a clinical database and operative records. Covariates of interest were extracted from electronic medical records. Timing and nature of the first cerebrovascular symptoms were also documented. The first medical contact and pathway of referral were also assessed. When possible, the ABCD2 score (age, blood pressure, clinical features, duration of symptoms, and diabetes) was calculated to calculate further risk of stroke. The nonparametric Wilcoxon test was used to assess differences in time intervals between two variables. The Kruskal-Wallis test was used to assess differences in time intervals in comparing more than two variables. A multivariate linear regression analysis was performed using covariates that were determined to be statistically significant in our sensitivity analyses. RESULTS: The cohort consisted of 111 patients with documented symptomatic carotid stenosis undergoing surgical intervention. Thirty-nine percent of all patients were operated on within 2 weeks from the first cerebrovascular symptoms. The median time between the occurrence of the first neurologic symptom and the CEA procedure was 25 (interquartile range [IQR], 11-85) days. The patient-dependent delay, defined as the median delay between the first neurologic symptom and the first medical contact, was 1 (IQR, 0-14) day. The medical-dependent delay was defined as the time interval between the first medical contact and CEA. This included the delay between the first medical contact and the request for surgery consultation (median, 3 [IQR, 1-10] days). The multivariate regression model demonstrated that the emergency physician as referral source (P = .0002) was statistically significant for reducing CEA delay. Patients who were investigated as an outpatient (P = .02), first medical contact with a general practitioner (P = .0002), and hospital center I as referral center (P = .045) were also found to be statistically significant to extend CEA delay when the model was adjusted over all covariates. In this center, there was no correlation between ABCD2 risk score and waiting time for surgery. CONCLUSIONS: The majority of our cohort falls short of the recommended 2-week interval to perform CEA. Factors contributing to reduced CEA delay were presentation to an emergency department, in-patient investigations, and a stroke center where a vascular surgeon is available. PMID- 27663930 TI - Estimating the excess lifetime risk of radiation induced secondary malignancy (SMN) in pediatric patients treated with craniospinal irradiation (CSI): Conventional radiation therapy versus helical intensity modulated radiation therapy. AB - PURPOSE: To quantify the risk of radiation-induced second malignancies (SMN) in pediatric patients receiving craniospinal irradiation (CSI) either with 3 dimensional conformal radiation therapy (Conv CSI) or tomotherapy helical intensity modulated radiation therapy (Tomo CSI). METHODS AND MATERIALS: A novel predictive model that accounts for short- and long-term carcinogenesis was incorporated into our institutional treatment planning system to quantify the lifetime risk of SMN in incidentally irradiated organs. Five pediatric patients previously treated with CSI were studied. For each case, Conv CSI and Tomo CSI plans were computed. The excess absolute number of SMN was computed for each plan for each patient. For female patients, age was varied to assess its impact. RESULTS: Tomo CSI has a much higher risk than Conv CSI for breast cancer. Tomo has a slightly increased risk for the lung, and conventional has a slightly higher risk for the thyroid. Both techniques have intermediate risks to the pancreas and stomach, and lesser risks to the bladder and rectum. For the breast, the magnitude of the absolute risks varied with age: 14.2% versus 7.4% (Tomo vs Conv) age 5; 16.9% versus 7.6% age 10, and 18.6% versus 8.0% age 15. CONCLUSIONS: Tomo has a higher risk for inducing breast and lung second cancers, and when using Tomo-based intensity modulated radiation therapy, care should be taken to avoid incidental radiation to the breast. When planning CSI, one needs to balance these cancer risks against other normal tissue effects. PMID- 27663931 TI - Long-term results on the efficacy of argon plasma coagulation for patients with chronic radiation proctitis after conventionally fractionated, dose-escalated radiation therapy for prostate cancer. AB - PURPOSE: This study was designed to assess the efficacy and outcomes of argon plasma coagulation (APC) in the management of chronic radiation proctitis after conventionally fractionated, dose-escalated radiation therapy (>=7560 cGy). METHODS AND MATERIALS: We retrospectively reviewed the charts on all patients treated with external beam radiation therapy (minimum dose, 7560 cGy) for histologically confirmed prostate cancer at our institution from 2003 to 2011. Five hundred patients met these criteria; of these, 35 patients (7.0%) developed radiation proctitis necessitating intervention with APC. Indications for APC treatment were either the need for blood transfusions resulting from proctitis related anemia or refractory bleeding despite medical management. RESULTS: The median follow-up from the completion of radiation treatment was 78 months (range, 19-129) and the median follow up from the most recent APC treatment was 56 months (range, 3-112). Fifteen men (42.9%) needed blood transfusions because of proctitis-related anemia. For 19 patients (54.3%), bleeding was controlled after 1 or 2 treatments. Eventual bleeding control was obtained in 30 patients (85.7%). The median number of sessions per patient was 2 (range, 1-13). Post-APC ulceration was noted in 8 cases (22.9%). Two patients (5.7%) developed colovesicular fistulas, with 1 patient dying from this complication. A short interval between treatments (<=35 days) was associated with an increased risk of ulcer or fistula formation. CONCLUSIONS: APC is an effective treatment for patients with medically refractive radiation proctitis after dose-escalated radiation therapy, frequently controlling bleeding after only one or two sessions. However, rectal ulceration is a common complication, along with a small risk of life-threatening toxicity. PMID- 27663932 TI - Online patient information from radiation oncology departments is too complex for the general population. AB - PURPOSE: Nearly two-thirds of cancer patients seek information about their diagnosis online. We assessed the readability of online patient education materials found on academic radiation oncology department Web sites to determine whether they adhered to guidelines suggesting that information be presented at a sixth-grade reading level. METHODS AND MATERIALS: The Association of American Medical Colleges Web site was used to identify all academic radiation oncology departments in the United States. One-third of these department Web sites were selected for analysis using a random number generator. Both general information on radiation therapy and specific information regarding various radiation modalities were collected. To test the hypothesis that the readability of these online educational materials was written at the recommended grade level, a panel of 10 common readability tests was used. A composite grade level of readability was constructed using the 8 readability measures that provide a single grade level output. RESULTS: A mean of 5605 words (range, 2058-12,837) from 30 department Web sites was collected. Using the composite grade level score, the overall mean readability level was determined to be 13.36 (12.83-13.89), corresponding to a collegiate reading level. This was significantly higher than the target sixth-grade reading level (middle school, t (29) = 27.41, P < .001). CONCLUSIONS: Online patient educational materials from academic radiation oncology Web sites are significantly more complex than recommended by the National Institutes of Health and the Department of Health and Human Services. To improve patients' comprehension of radiation therapy and its role in their treatment, our analysis suggests that the language used in online patient information should be simplified to communicate the information at a more appropriate level. PMID- 27663934 TI - Here/In This Issue and There/Abstract Thinking: The Neurobiology of Comorbidity. PMID- 27663933 TI - Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence Based Guideline. AB - PURPOSE: The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice. METHODS AND MATERIALS: A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations. RESULTS: Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panel's conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy. CONCLUSION: Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patient's overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment including prior radiation at or near current site of treatment, tumor and normal tissue response history to local and systemic therapies, and other factors related to the patient, tumor characteristics, or treatment. PMID- 27663935 TI - In Their Own Words: Immigration and Pediatric Mental Health in 2016. PMID- 27663936 TI - Machine Learning: A Primer for Child Psychiatrists. PMID- 27663937 TI - Intravenous Immunoglobulin Is Not an Effective Treatment for Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infection Obsessive Compulsive Disorder. PMID- 27663938 TI - The Genetics of Attention-Deficit/Hyperactivity Disorder: Failure or Learning Process? PMID- 27663939 TI - Long-Term Outcomes of Attention-Deficit/Hyperactivity Disorder and Conduct Disorder: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) are common externalizing disorders. Despite previous research demonstrating that both are longitudinally associated with adverse outcomes, there have been no systematic reviews examining all of the available evidence linking ADHD and CD with a range of health and psychosocial outcomes. METHOD: Electronic databases (EMBASE, Medline, and PsycINFO) were searched for studies published from 1980 up to March 2015. Published cohort and case-control studies were included if they reported a longitudinal association between ADHD or CD and adverse outcomes with a minimum follow-up of 2 years. Outcomes with sufficient data were pooled in a random effects meta-analysis to give overall odds ratios (ORs) with corresponding 95% CIs. RESULTS: Of the 278 studies assessed, 114 met inclusion criteria and 98 were used in subsequent meta-analyses. ADHD was associated with adverse outcomes including academic achievement (e.g. failure to complete high school; odds ratio [OR] = 3.7, 95% CIs 2.0-7.0), other mental and substance use disorders (e.g. depression; OR = 2.3, 1.5-3.7), criminality (e.g. arrest; OR = 2.4, 1.5-3.8), and employment (e.g., unemployment; OR = 2.0, 1.0-3.9). CD was associated with outcomes relating to academic achievement (e.g. failure to complete high school; OR = 2.7, 1.5-4.7), other mental and substance use disorders (e.g., illicit drug use; OR = 2.1, 1.7-2.6), and criminality (e.g. violence; OR = 3.5, 2.3-5.3). CONCLUSION: This study demonstrated that ADHD and CD are associated with disability beyond immediate health loss. Although the analyses could not determine the mechanisms behind these longitudinal associations, they demonstrate the importance of addressing ADHD and CD early in life so as to potentially avert a wide range of future adverse outcomes. PMID- 27663940 TI - Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors and Clomipramine in Pediatric Obsessive-Compulsive Disorder. AB - OBJECTIVE: We conducted a meta-analysis to examine the following: the time course of response to selective serotonin reuptake inhibitors (SSRIs) and clomipramine in pediatric obsessive-compulsive disorder (OCD); whether higher doses of SSRIs are associated with an improved response in pediatric OCD; differences in efficacy among SSRI agents; differences in efficacy between SSRIs and clomipramine; and whether the time course and magnitude of response to SSRIs are different in pediatric and adult patients with OCD. METHOD: We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs (or clomipramine) to placebo for the treatment of pediatric OCD and using the Children's Yale-Brown Obsessive-Compulsive Scale as an outcome. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on weighted mean differences between the treatment and placebo groups. RESULTS: Nine trials involving 801 children with OCD were included in this meta-analysis. A logarithmic model indicating that the greatest benefits occurred early in treatment best fit the longitudinal data for both clomipramine and SSRIs. Clomipramine was associated with a greater measured benefit compared to placebo than SSRIs. There was no evidence for a relationship between SSRI dosing and treatment effect, although data were limited. Adults and children with OCD demonstrated a similar degree and time course of response to SSRIs in OCD. CONCLUSION: These results suggest that the greatest incremental treatment gains in pediatric OCD occur early in SSRI treatment (similar to adults with OCD and children and adults with major depression). PMID- 27663941 TI - Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. AB - OBJECTIVE: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS. METHOD: A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. "Responders" were defined, a priori, by a >= 30% decrease in CY-BOCS total score, and a "much" or "very much" improved rating on CGI-I. RESULTS: During the double-blind phase, the mean decrease in CY-BOCS score was 24% +/- 31% in the IVIG group (n = 17) and 12% +/- 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% +/- 33% at week 12 and 62% +/- 33% at week 24. CONCLUSION: IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666. PMID- 27663943 TI - Age and DRD4 Genotype Moderate Associations Between Stimulant Treatment History and Cortex Structure in Attention-Deficit/Hyperactivity Disorder. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with dopaminergic imbalance and subtle volume decreases in the brain. Stimulants acutely enhance dopaminergic neurotransmission. Long-term effects of prolonged manipulation of the dopaminergic system on brain structure remain poorly understood; they could be beneficial or unfavorable and could be moderated by common genetic variants and/or age. METHOD: In a large observational ADHD cohort study (N = 316), the effects of cumulative stimulant treatment, genotype (for DAT1 haplotype and DRD4 variants), and treatment-by-genotype interactions on striatal, frontal, and hippocampal volumes and their interactions with age were evaluated. RESULTS: No main effects of treatment were found. Associations between treatment and bilateral frontal and left hippocampal volume depended on DRD4 genotype and age. At a younger age and lower treatment levels, but not at a younger age and higher treatment levels, carriers of the DRD4 7R allele showed decreased frontal cortex volumes. At an older age, carriers and non-carriers showed smaller frontal volumes irrespective of treatment history. Left hippocampal volume was similar to that in controls at average treatment levels and increased with treatment only in carriers of the DRD4 risk allele and at a younger age. No interaction effects were found in the striatum. CONCLUSION: Carriers of the DRD4 risk allele at a younger age might be sensitive to cortical remodeling after stimulant treatment. The cross-sectional nature of this study warrants cautious interpretation of age effects. The present findings, although of small effect size, might ultimately contribute to optimal care for individuals with ADHD. PMID- 27663942 TI - Atomoxetine and Parent Training for Children With Autism and Attention Deficit/Hyperactivity Disorder: A 24-Week Extension Study. AB - OBJECTIVE: The authors previously reported on a 2-by-2 randomized clinical trial of individual and combined treatment with atomoxetine (ATX) and parent training (PT) for attention-deficit/hyperactivity disorder (ADHD) symptoms and behavioral noncompliance in 128 5- to 14-year-old children with autism spectrum disorder. In the present report, they describe a 24-week extension of treatment responders and nonresponders. METHOD: One-hundred seventeen participants from the acute trial (91%) entered the extension; 84 of these were in 2 subgroups: "treatment responders" (n = 43) from all 4 groups in the acute trial, seen monthly for 24 weeks, and "placebo nonresponders" (n = 41), treated with open-label ATX for 10 weeks. Participants originally assigned to PT continued PT during the extension; the remainder served as controls. Primary outcome measurements were the parent rated Swanson, Nolan and Pelham ADHD scale and the Home Situations Questionnaire. RESULTS: Sixty percent (26 of 43) of treatment responders in the acute trial, including 68% of responders originally assigned to ATX, still met the response criteria at the end of the extension. The response rate of placebo nonresponders treated with 10-week open-label ATX was 37% (15 of 41), similar to the acute trial. Children receiving open-label ATX + PT were significantly more likely to be ADHD responders (53% versus 23%) and noncompliance responders (58% versus 14%) than those receiving open-label ATX alone. CONCLUSION: Most ATX responders maintained their responses during the extension. PT combined with ATX in the open label trial appeared to improve ADHD and noncompliance outcomes more than ATX alone. Clinical trial registration information-Atomoxetine, Placebo and Parent Management Training in Autism (Strattera); http://clinicaltrials.gov; NCT00844753. PMID- 27663944 TI - Relative Immaturity in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Early Adulthood: Exploring Genetic and Environmental Overlap Across Development. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been linked to immaturity relative to peers in childhood, yet it is unclear how such immaturity is associated with ADHD across development. This longitudinal twin study examined the genetic and environmental contributions to the association between parents' perception of their child's immaturity relative to peers (RI) in childhood and ADHD symptoms across development. METHOD: 1,302 twin pairs from the Swedish Twin Study of Child and Adolescent Development were followed prospectively from childhood to early adulthood. Parent ratings of RI were collected at 8 to 9 years and parent and self-ratings of ADHD symptoms were collected at 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years using the Child Behavior Checklist Attention Problems scale. In addition, ADHD symptoms corresponding to DSM criteria were used for sensitivity analysis. Analyses were conducted using longitudinal structural equation modeling with multiple raters. RESULTS: RI-related etiologic factors, predominantly influenced by genes, explained 10-14% of the variance in ADHD symptoms from 8 to 9 up to 16 to 17 years. The influence of these RI-related factors on ADHD symptoms attenuated to 4% by 19 to 20 years of age. The remaining variance in ADHD symptoms was primarily explained by genetic factors independent of RI, which remained relatively stable across development, explaining 19% to 30% of the variance in ADHD symptoms from 13 to 14 up to 19 to 20 years. CONCLUSION: The results show that RI is significantly associated with ADHD symptoms, particularly during childhood and adolescence, and that the association is primarily explained by a shared genetic liability. Nevertheless, the magnitude of associations across development was modest, highlighting that RI is merely one aspect contributing to the complex etiology of ADHD symptoms. PMID- 27663947 TI - Fun and Games. PMID- 27663948 TI - Corrigendum. PMID- 27663946 TI - Withdrawn/Depressed Behaviors and Error-Related Brain Activity in Youth With Obsessive-Compulsive Disorder. AB - OBJECTIVE: The pathophysiology of obsessive-compulsive disorder (OCD) involves increased activity in corticostriatal circuits connecting the anterior cingulate cortex with other brain regions. The error-related negativity (ERN) is a negative deflection in the event-related potential after an incorrect response that is believed to reflect anterior cingulate cortex activity. This study examined the relation of the ERN to OCD symptom dimensions and other childhood symptom dimensions. METHOD: The ERN, correct response negativity, and accuracy were measured during a flanker task to assess performance monitoring in 80 youth with a lifetime diagnosis of OCD and 80 matched healthy comparison participants ranging from 8 to 18 years old. The relation of the ERN to OCD symptom dimension scores and Child Behavior Checklist Syndrome Scale scores was examined in multiple linear regression analyses. RESULTS: Accuracy was significantly decreased and ERN amplitude was significantly increased in patients compared with controls. ERN amplitude in patients was significantly correlated with accuracy, but not with OCD symptom dimensions, severity, comorbidity, or treatment. In a multiple linear regression analysis using age, accuracy, OCD, and Child Behavior Checklist Syndrome Scale scores as predictors of ERN amplitude, the ERN had significant associations only with Withdrawn/Depressed Scale scores and accuracy. CONCLUSION: An enlarged ERN is a neural correlate of pediatric OCD that is independent of OCD symptom expression and severity. The finding of lower accuracy in pediatric cases requires replication. The relation between an enhanced ERN and withdrawn/depressed behaviors warrants further research in youth with OCD and other internalizing disorders. PMID- 27663949 TI - Bioactive benzofuran-chalcanes as potential NQO1 inducers from Millettia pulchra (Benth) kurzvar-laxior (Dunn) Z.Wei. AB - Five chalcanes ((alpha'R)-2, alpha'-dimethoxy-furano-[4", 5'': 3', 4'] chalcane, (alpha'R, betaR)-2', alpha', beta-trimethoxy-furano-[4", 5'': 3', 4'] chalcane, (alpha'S, betaR)-2', alpha', beta-trimethoxy-furano-[4", 5'': 3', 4'] chalcane, (alpha'R, betaR)-2', beta-dimethoxy-alpha'-hydroxyethoxy-furano-[4", 5'': 3', 4'] chalcane, (alpha'S, betaR)-2', beta-dimethoxy-alpha'-hydroxyethoxy-furano-[4", 5'': 3', 4'] chalcane) and a flavonoid glycoside (3', 7-dihydroxy-6-methoxy-4', 5'-methylenedioxyisoflavone 6-O-beta-D- glucopyranoside), together with 15 known components, were isolated from the leaves of Millettia pulchra (Benth) Kurzvar laxior (Dunn) Z. Wei, a traditional Zhuang medicine. Their chemical structures were established by extensive analysis of NMR, mass spectrometry and ECD spectra. Furthermore compounds (alpha'R, betaR)-2', beta-dimethoxy-alpha'-hydroxyethoxy furano-[4", 5'': 3', 4'] chalcane, (alpha'S, betaR)-2', beta-dimethoxy-alpha' hydroxyethoxy-furano-[4", 5'': 3', 4'] chalcane, quercetin, methyl 2-O-beta-D glucopyranosylbenzoate, 6,7-dimethoxy-3',4'-methylenedioxyisoflavone and lyoniresinol were suggested to be potential chemopreventive agents because of their significant activity in inducing NQO1 ([NAD(P)H quinine oxidoreductase 1], a phase II metabolism enzyme). PMID- 27663950 TI - Multiple training interventions significantly improve reproducibility of PET/CT based lung cancer radiotherapy target volume delineation using an IAEA study protocol. AB - BACKGROUND AND PURPOSE: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting. MATERIAL AND METHODS: Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy. RESULTS: Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57+/-0.07 to 0.66+/-0.07. The overall mean surface distance between observer and expert contours decreased from -0.40+/-0.03cm to -0.01+/-0.33cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64+/-0.06 to 0.80+/-0.05 (p=0.01). Mean surface distances decreased from -0.34+/-0.16cm to 0.05+/-0.20cm (p=0.01). CONCLUSION: Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduce interobserver variation. PMID- 27663951 TI - Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis. AB - PURPOSE: To determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade?2 (fibrosis RTOG2-4) at 6months following R(C)T for HNC. MATERIAL/METHODS: 161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG2-4 6months after the end of treatment. RESULTS: Radiodermatitis at the end of R(C)T ?grade 3 proved to be associated with the incidence of fibrosis RTOG2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade?3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92. CONCLUSION: A model for the prediction of fibrosis RTOG2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade?3 at the end of R(C)T is associated with RTOG2-4 fibrosis at 6months. PMID- 27663952 TI - Kilovoltage intrafraction monitoring for real-time image guided adaptive radiotherapy reduces total dose for lung SABR. AB - This study presents estimation of typical kV fluoroscopic imaging doses for image guided real-time adaptive radiotherapy. For a cohort of 10 lung SABR patients the estimated imaging dose to ipsi-lateral lung with real-time adaptation is 9.9 15.1cGy, which is less than the extra lung dose from treatment with potentially larger ITV-based PTV approach. PMID- 27663945 TI - A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts. AB - OBJECTIVE: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. METHOD: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. RESULTS: SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 * 10(-6) and 2.66 * 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. CONCLUSION: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants. PMID- 27663953 TI - Autosomal dominant hypocalcaemia: A novel mutation. PMID- 27663954 TI - Building better health. PMID- 27663955 TI - Renoprotection in LEADER and EMPA-REG OUTCOME. PMID- 27663957 TI - Strengthening of information systems and research to tackle HIV and non communicable diseases. PMID- 27663956 TI - SGLT2 inhibitors: beta blockers for the kidney? PMID- 27663958 TI - Research digest: weight loss to prevent and treat diabetes. PMID- 27663961 TI - Palliative care in Dutch hospitals: a rapid increase in the number of expert teams, a limited number of referrals. AB - BACKGROUND: Palliative care expert teams in hospitals have positive effects on the quality of life and satisfaction with care of patients with advanced disease. Involvement of these teams in medical care is also associated with substantial cost savings. In the Netherlands, professional standards state that each hospital should have a palliative care team by 2017. We studied the number of hospitals that have a palliative care team and the characteristics of these teams. METHODS: In April 2015, questionnaires were mailed to key palliative care professionals in all general, teaching and academic hospitals in the Netherlands. Out of 92 hospitals, 74 responded (80 %). RESULTS: Seventy-seven percent of all participating hospitals had a palliative care team. Other services, such as outpatient clinics (22 %), palliative care inpatient units (7 %), and palliative day care facilities (4 %) were relatively scarce. The mean number of disciplines that were represented in the teams was 6,5. The most common disciplines were nurses (72 %) and nurse practitioners (54 %), physicians specialized in internal medicine (90 %) or anaesthesiology (75 %), and spiritual caregivers (65 %). In most cases, the physicians did not have labeled hours available for their work as palliative care consultant, whereas nurses and nurse practitioners did. Most teams (77 %) were only available during office hours. Twenty-six percent of the teams could not only be consulted by healthcare professionals but also by patients or relatives. The annual number of consultations for inpatients per year ranged from 2 to 680 (median: 77). On average, teams were consulted for 0.6 % of all patients admitted to the hospitals. CONCLUSION: The number of Dutch hospitals with a palliative care team is rapidly increasing. There are substantial differences between teams regarding the disciplines represented in the teams, the procedures and the number of consultations. The development of quality standards and adequate staffing of the teams could improve the quality and effectiveness of the teams. PMID- 27663960 TI - Recurrence of coronary arteriovenous fistulae in a rare case of bilateral right coronary and circumflex artery arteriovenous fistulae to the pulmonary artery. PMID- 27663962 TI - Identification of Potential Key Long Non-Coding RNAs and Target Genes Associated with Pneumonia Using Long Non-Coding RNA Sequencing (lncRNA-Seq): A Preliminary Study. AB - BACKGROUND This study aimed to identify the potential key long non-coding RNAs (lncRNAs) and target genes associated with pneumonia using lncRNA sequencing (lncRNA-seq). MATERIAL AND METHODS A total of 9 peripheral blood samples from patients with mild pneumonia (n=3) and severe pneumonia (n=3), as well as volunteers without pneumonia (n=3), were received for lncRNA-seq. Based on the sequencing data, differentially expressed lncRNAs (DE-lncRNAs) were identified by the limma package. After the functional enrichment analysis, target genes of DE lncRNAs were predicted, and the regulatory network was constructed. RESULTS In total, 99 DE-lncRNAs (14 upregulated and 85 downregulated ones) were identified in the mild pneumonia group and 85 (72 upregulated and 13 downregulated ones) in the severe pneumonia group, compared with the control group. Among these DE lncRNAs, 9 lncRNAs were upregulated in both the mild and severe pneumonia groups. A set of 868 genes were predicted to be targeted by these 9 DE-lncRNAs. In the network, RP11-248E9.5 and RP11-456D7.1 targeted the majority of genes. RP11 248E9.5 regulated several genes together with CTD-2300H10.2, such as QRFP and EPS8. Both upregulated RP11-456D7.1 and RP11-96C23.9 regulated several genes, such as PDK2. RP11-456D7.1 also positively regulated CCL21. CONCLUSIONS These novel lncRNAs and their target genes may be closely associated with the progression of pneumonia. PMID- 27663965 TI - Increasing Universal Lipid Screening Among 9- to 11-Year-Old Children Through a Quality Improvement Initiative. AB - In 2011, the National Heart Lung and Blood Institute recommended universal lipid screening (ULS) in 9- to 11-year-old children. This study aimed to determine whether a quality improvement (QI) initiative increased ULS. Data were abstracted from the electronic medical record to compare screening behaviors 1 year preimplementation and postimplementation. A focus group was conducted to examine physicians' attitudes. In preimplementation and postimplementation years, the number of 9- to 11-year-olds seen for well-child checks were 356 and 357, respectively. The first and second phases of the intervention were associated with a 64.3% ( P < .001) and 2.3% ( P = .75) increase in ordering, respectively. The rate of abnormal results was similar (21.4% vs 20.1%, P = .91). Physicians reported "some benefits" to screening but expressed concerns about cost effectiveness and impact. The QI initiative resulted in high rates of ULS. Nonetheless, physicians continue to question the impact of screening on long-term health. More research on the benefits, costs, and outcomes of ULS is needed. PMID- 27663964 TI - A 10-Year Review of Necrotizing Fasciitis in the Pediatric Population: Delays to Diagnosis and Management. AB - OBJECTIVE: To assess the promptness and appropriateness of management in pediatric cases of necrotizing fasciitis (NF). METHODS: A retrospective chart review examined cases of pediatric NF treated at a pediatric tertiary care center over a 10-year period. RESULTS: Twelve patients were identified over the 10-year period. The median (25th to 75th centile) times to appropriate antibiotic administration, infectious disease consults, surgical consults and debridement surgeries were 2.6 (2.1-3.2), 7.7 (3.4-24.4), 4.6 (1.7-21.0), and 22.1 (10.3 28.4) hours following assessment at triage. The initial antibiotic(s) administered covered the causative organism in 9 of 12 cases. The median (25th to 75th centile) length of hospital stay was 21 (14.0-35.5) days. CONCLUSIONS: The large variability in the care of these patients speaks to the range of their presenting symptomatology. The lack of a standardized approach to the pediatric patient with suspected NF results in delays in management and suboptimal antibiotic choice. PMID- 27663963 TI - c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium. AB - M cells reside within the follicle-associated epithelium (FAE) overlying the gut associated lymphoid tissues. These unique phagocytic epithelial cells enable the mucosal immune system to sample antigens within the lumen of the intestine. The differentiation of M cells from uncommitted precursors in the FAE is dependent on the production of receptor activator of nuclear factor-kappaB ligand (RANKL) by subepithelial stromal cells. The ligation of a variety of cell surface receptors activates the nuclear factor-kappaB (NF-kappaB) family of transcription factors which in-turn induce the transcription of multiple target genes. RANKL stimulation can stimulate the nuclear translocation of the NF-kappaB subunit c Rel. We therefore used c-Rel-deficient mice to determine whether the differentiation and functional maturation of M cells in the Peyer's patches was dependent on c-Rel. Our data show that c-Rel-deficiency does not influence the expression of RANKL or RANK in Peyer's patches, or the induction of M-cell differentiation in the FAE. RANKL-stimulation in the differentiating M cells induces the expression of SpiB which is essential for their subsequent maturation. However, SpiB expression in the FAE was also unaffected in the absence of c-Rel. As a consequence, the functional maturation of M cells was not impaired in the Peyer's patches of c-Rel-deficient mice. Although our data showed that the specific expression of CCL20 and ubiquitin D in the FAE was not impeded in the absence of c-Rel, the expression of ubiquitin D was dramatically reduced in the B cell-follicles of c-Rel-deficient mice. Coincident with this, we also observed that the status of follicular dendritic cells in the B cell-follicles was dramatically reduced in Peyer's patches from c-Rel-deficient mice. Taken together, our data show that c-Rel is dispensable for the RANKL-mediated differentiation and functional maturation of M cells. PMID- 27663966 TI - Payments to Pediatricians in the Sunshine Act. AB - Under the Sunshine Act, pharmaceutical and product industry payments to physicians are reported in a public database. We sought to characterize payments received by pediatricians in the first full year of disclosures in 2014. We used the National Centers for Medicare and Medicaid Services Open Payment files to identify pediatricians who received payments. Payment characteristics were stratified, and descriptive statistical analysis was performed, including mean, median, and ranges of payments. Between January 1, 2014, and December 31, 2014, 35 697 pediatricians received payments amounting to $30 031 960. General pediatricians received the majority of payments (71%). Median payment was $15 (interquartile range = $12-$24), mostly in the form of noncash items and services (84%). Significant diversity was observed in median payments among specialty providers. In conclusion, 42% of US pediatricians received industry payments in 2014. These data provide a foundation for future research regarding the influence of the Sunshine Act on pediatric clinical practices. PMID- 27663967 TI - Interactive effects of AM251 and baclofen on synaptic plasticity in the rat dentate gyrus. AB - Long-term potentiation (LTP), a form of synaptic plasticity, is considered to be a critical cellular mechanism that underlies learning and memory. Cannabinoid CB1 and metabotropic GABAB receptors display similar pharmacological effects and co localize in certain brain regions. In this study, we examined the effects of co administration of the CB1 and GABAB antagonists AM251 and baclofen, respectively, on LTP induction in the rat dentate gyrus (DG). Male Wistar rats were anesthetized with urethane. A stimulating electrode was placed in the lateral perforant path (PP), and a bipolar recording electrode was inserted into the DG until maximal field excitatory postsynaptic potentials (fEPSPs) were observed. LTP was induced in the hippocampal area by high-frequency stimulation (HFS) of the PP. fEPSPs and population spikes (PS) were recorded at 5, 30, and 60min after HFS in order to measure changes in the synaptic responses of DG neurons. Our results showed that HFS coupled with administration of AM251 and baclofen increased both PS amplitude and fEPSP slope. Furthermore, co-administration of AM251 and baclofen elicited greater increases in PS amplitude and fEPSP slope. The results of the present study suggest that CB1 receptor activation in the hippocampus mainly modifies synapses onto GABAergic interneurons located in the DG. Our results further suggest that, when AM251 and baclofen are administered simultaneously, AM251 can alter GABA release and thereby augment LTP through GABAB receptors. These results suggest that functional crosstalk between cannabinoid and GABA receptors regulates hippocampal synaptic plasticity. PMID- 27663968 TI - Transarterial regional hypothermia provides robust neuroprotection in a rat model of permanent middle cerebral artery occlusion with transient collateral hypoperfusion. AB - The robust neuroprotective effects of transarterial regional hypothermia have been demonstrated in the typical transient middle cerebral artery occlusion (tMCAO) model, but have not yet been tested in other ischemic stroke models, even though clinical ischemic conditions are diverse. In order to clarify these effects in a different ischemic stroke model, we employed a rat model of permanent MCAO (pMCAO) with transient collateral hypoperfusion (tCHP), which was achieved by direct MCA ligation through craniotomy and 1-h bilateral common carotid artery occlusion at the beginning of pMCAO. The infusion of 20ml/kg of 4 degrees C cold saline (CS) or 37 degrees C warm saline (WS) into the ipsilateral internal carotid artery (ICA) was performed for 15min in intra- or post-tCHP. Neurological scores, infarct/edema volumes, and neuronal apoptosis and reactive gliosis were compared between the CS and WS groups and a non-infusion control group after 48h of reperfusion. Although brain temperatures were only reduced by 2-3 degrees C for 15min, the CS group had significantly better neurological scores, smaller infarct/edema volumes, and less penumbral neuronal apoptosis and reactive gliosis than the control and WS groups. The post-tCHP CS group exhibited prominent neuroprotective effects, even though infarct volumes and neuronal apoptosis were reduced less than those in the intra-tCHP CS group. In conclusion, we demonstrated the neuroprotective effects of transarterial regional hypothermia in an ischemic model of pMCAO with tCHP. Even though MCAO is persistent, cold infusion via the ICA is neuroprotective for the penumbra, suggesting the wider therapeutic application of this therapy. PMID- 27663969 TI - Stress-based animal models of depression: Do we actually know what we are doing? AB - Depression is one of the leading causes of disability and a significant health concern worldwide. Much of our current understanding on the pathogenesis of depression and the pharmacology of antidepressant drugs is based on pre-clinical models. Three of the most popular stress-based rodent models are the forced swimming test, the chronic mild stress paradigm and the learned helplessness model. Despite their recognizable advantages and limitations, they are associated with an immense variability due to the high number of design parameters that define them. Only few studies have reported how minor modifications of these parameters affect the model phenotype. Thus, the existing variability in how these models are used has been a strong barrier for drug development as well as benchmark and evaluation of these pre-clinical models of depression. It also has been the source of confusing variability in the experimental outcomes between research groups using the same models. In this review, we summarize the known variability in the experimental protocols, identify the main and relevant parameters for each model and describe the variable values using characteristic examples. Our view of depression and our efforts to discover novel and effective antidepressants is largely based on our detailed knowledge of these testing paradigms, and requires a sound understanding around the importance of individual parameters to optimize and improve these pre-clinical models. PMID- 27663970 TI - Magnetic resonance spectroscopic analysis of neurometabolite changes in the developing rat brain at 7T. AB - We utilized proton magnetic resonance spectroscopy to evaluate the metabolic profile of the hippocampus and anterior cingulate cortex of the developing rat brain from postnatal days 14-70. Measured metabolite concentrations were modeled using linear, exponential, or logarithmic functions and the time point at which the data reached plateau (i.e. when the portion of the data could be fit to horizontal line) was estimated and was interpreted as the time when the brain has reached maturity with respect to that metabolite. N-acetyl-aspartate and myo inositol increased within the observed period. Gluthathione did not vary significantly, while taurine decreased initially and then stabilized. Phosphocreatine and total creatine had a tendency to increase towards the end of the experiment. Some differences between our data and the published literature were observed in the concentrations and dynamics of phosphocreatine, myo inositol, and GABA in the hippocampus and creatine, GABA, glutamine, choline and N-acetyl-aspartate in the cortex. Such differences may be attributed to experimental conditions, analysis approaches and animal species. The latter is supported by differences between in-house rat colony and rats from Charles River Labs. Spectroscopy provides a valuable tool for non-invasive brain neurochemical profiling for use in developmental neurobiology research. Special attention needs to be paid to important sources of variation like animal strain and commercial source. PMID- 27663971 TI - Functional modulation of strychnine-sensitive glycine receptors in rat hippocampal pyramidal neurons by amyloid-beta protein (1-42). AB - Amyloid-beta peptide (Abeta) is considered a key protein in the pathogenesis of Alzheimer's disease because of its neurotoxicity, resulting in impaired synaptic function and memory. On the other hand, it was demonstrated that low (picomolar) concentrations of Abeta enhance synaptic plasticity and memory, suggesting that in the healthy brain, physiological Abeta concentrations are necessary for normal cognitive functions. In the present study, we found that Abeta (1-42) in concentrations of 10 pM - 100nM enhanced desensitization of the glycine-activated current in isolated CA3 pyramidal neurons and also reversibly suppressed its peak amplitude during short (600ms) co-application with agonist. The effect was most prominent at low glycine concentrations. When glycine receptors were activated by other receptor agonists - taurine and beta-alanine, the changes of current kinetics and amplitudes induced by Abeta had a similar character. When Abeta (100 pM) was added to the bath solution, it caused, besides acceleration of desensitization, more pronounced reduction of peak current amplitude. This effect developed slowly, during a few minutes, and was more prominent at saturating concentrations of agonists. The results suggest that Abeta interacts with glycine receptors through three different mechanisms - by enhancing receptor desensitization, by rapid inhibition of the receptor, and also by means of a slowly developing inhibition of the amplitude of the current, possibly through intracellular mechanisms. The observed changes in the activity of glycine receptors induced by Abeta can lead to suppression of the tonic inhibition of hippocampal neurons mediated by extrasynaptic glycine receptors. PMID- 27663972 TI - In utero methoxychlor exposure increases rat fetal Leydig cell number but inhibits its function. AB - The objective of the present study is to determine whether in utero exposure to methoxychlor (MXC) affects rat fetal Leydig cell number, cell size, or functions. Pregnant Sprague Dawley dams were gavaged with corn oil (control, 0mg/kg/day MXC) or MXC at doses of 10, 50, or 100mg/kg/day from gestational day (GD) 12 to 21. The results show that MXC increased fetal Leydig cell numbers dose-dependently from 95+/-8*103 cells/testis (control, mean+/-SEM) to 101+/-6, 148+/-22, and 168+/-21*103 cells/testis, at the doses of 10, 50, and 100mg/kg, respectively. The increase of Leydig cell number by MXC was contributed by the increase of single cell population of Leydig cells, which increased from 21+/-2% of the control to 31+/-4%, 39+/-3%, or 40+/-4% at the doses of 10, 50 or 100mg/kg, respectively. Quantitative PCR results show that MXC increased Lhcgr expression at dose of 10mg/kg and Scarb1 and Cyp11a1 mRNA levels at doses of 50 and 100mg/kg. Immunohistochemical staining demonstrated the increase of CYP11A1 protein level from the dose of 10mg/kg. However, at the highest dose (100mg/kg) MXC reduced the testicular testosterone level and MXC (1MUM) in vitro treatment also inhibited androgen production from isolated fetal Leydig cells. In conclusion, our findings indicate that at low dose MXC may increase fetal Leydig cell numbers and the expressions of some steroidogenic enzymes, but at high dose it reduces the testicular testosterone level leading to reproductive tract malformations in the male offspring. PMID- 27663973 TI - Andrographolide induces Nrf2 and heme oxygenase 1 in astrocytes by activating p38 MAPK and ERK. AB - BACKGROUND: Andrographolide is the major labdane diterpenoid originally isolated from Andrographis paniculata and has been shown to have anti-inflammatory and antioxidative effects. However, there is a dearth of studies on the potential therapeutic utility of andrographolide in neuroinflammatory conditions. Here, we aimed to investigate the mechanisms underlying andrographolide's effect on the expression of anti-inflammatory and antioxidant heme oxygenase-1 (HO-1) in primary astrocytes. METHODS: Measurements of the effects of andrograholide on antioxidant HO-1 and its transcription factor, Nrf2, include gene expression, protein turnover, and activation of putative signaling regulators. RESULTS: Andrographolide potently activated Nrf2 and also upregulated HO-1 expression in primary astrocytes. Andrographolide's effects on Nrf2 seemed to be biphasic, with acute (within 1 h) reductions in Nrf2 ubiquitination efficiency and turnover rate, followed by upregulation of Nrf2 mRNA between 8 and 24 h. The acute regulation of Nrf2 by andrographolide seemed to be independent of Keap1 and partly mediated by p38 MAPK and ERK signaling. CONCLUSIONS: These data provide further insights into the mechanisms underlying andrographolide's effects on astrocyte-mediated antioxidant, and anti-inflammatory responses and support the further assessment of andrographolide as a potential therapeutic for neurological conditions in which oxidative stress and neuroinflammation are implicated. PMID- 27663974 TI - Evaluation of the sensitizing potential of food proteins using two mouse models. AB - The current methodology to identify allergenic food proteins is effective in identifying those that are likely to cross-react with known allergens. However, most assays show false positive results for low/non-allergens. Therefore, an ex vivo/in vitro DC-T cell assay and an in vivo mouse model were used to distinguish known allergenic food proteins (Ara h 1, beta-Lactoglobulin, Pan b 1, bovine serum albumin, whey protein isolate) from low/non allergenic food proteins (soy lipoxygenase, gelatin, beef tropomyosin, rubisco, Sola t 1). CD4+ T cells from protein/alum-immunized mice were incubated with corresponding protein-pulsed bone marrow-derived DC and analyzed for cytokine release. All known allergens induced Th2 responses in vitro, whereas soy lipoxygenase, gelatin or beef tropomyosin did not. Sola t 1 and rubisco induced a more generalized T cell response due to endotoxin contamination, indicating the endotoxin-sensitivity of the DC-T assay. To analyze responses in vivo, mice were orally sensitized on days 0 and 7. Known allergens induced IgE and mMCP-1 release upon oral challenge at day 16, whereas the low/non-allergens did not. Both the DC-T cell assay and the mouse model were able to distinguish 5 known allergens from 5 low/non-allergens and may be useful to identify novel allergenic food proteins. PMID- 27663975 TI - Prevention of adhesions in the temporomandibular joint by the use of chitosan membrane in goats. AB - We evaluated the effects of chitosan membrane, a highly absorbable and viscous material, in the prevention of intra-articular adhesions after anchoring of the disc in the temporomandibular joints (TMJ) of six adult goats (12 joints). To simulate anterior displacement of the disc and TMJ trauma, we cut off the retrodiscal attachment and damaged the surface of the condylar bone, then randomly divided the goats into two groups: the control group (n=2) and the experimental group (n=4). In the experimental group we covered the condylar surfaces on both sides of the animals with chitosan membranes. Those in the control group had operations and no special treatment. We took magnetic resonance images (MRI) of all the animals before the operation and at three and six months postoperatively, and measured the interincisal opening and strength at the same time. We counted the number of adhesions macroscopically, and evaluated the adhesive tissues, cartilage, and subchondral bony changes histologically and immunohistochemically. Measurements of the interincisal opening and strength were significantly better in the experimental group than in the controls (p<0.05). Macroscopic evaluation (using a specific adhesion scoring system) showed a significant difference in the formation of adhesions between the groups (p<0.05). Although MRI showed no significant difference between the groups, the histological and immunohistochemical observations supported the hypothesis that chitosan membrane could prevent intra-articular adhesions. It seems to inhibit the formation of adhesions effectively and promote repair of the cartilage. It may therefore be considered a promising absorbable biomaterial to prevent adhesions after operations on the TMJ. PMID- 27663976 TI - Importance of knowing what drugs the patient has taken in the referral pathway for suspected cancer. PMID- 27663977 TI - Novel regional age-associated DNA methylation changes within human common disease associated loci. AB - BACKGROUND: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. RESULTS: In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19-82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect, with 80.3 % and 53.5 % replicated to p < 0.05 and p < 1.85 * 10-8, respectively. CONCLUSION: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identify novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases. PMID- 27663979 TI - eRegistries: governance for electronic maternal and child health registries. AB - BACKGROUND: The limited availability of maternal and child health data has limited progress in reducing mortality and morbidity among pregnant women and children. Global health agencies, leaders, and funders are prioritizing strategies that focus on acquiring high quality health data. Electronic maternal and child health registries (eRegistries) offer a systematic data collection and management approach that can serve as an entry point for preventive, curative and promotive health services. Due to the highly sensitive nature of reproductive health information, careful consideration must be accorded to privacy, access, and data security. In the third paper of the eRegistries Series, we report on the current landscape of ethical and legal governance for maternal and child health registries in developing countries. METHODS: This research utilizes findings from two web-based surveys, completed in 2015 that targeted public health officials and health care providers in 76 countries with high global maternal and child mortality burden. A sample of 298 public health officials from 64 countries and 490 health care providers from 59 countries completed the online survey. Based on formative research in the development of the eRegistries Governance Guidance Toolkit, the surveys were designed to investigate topics related to maternal and child health registries including ethical and legal issues. RESULTS: According to survey respondents, the prevailing legal landscape is characterized by inadequate data security safeguards and weak support for core privacy principles. Respondents from the majority of countries indicated that health information from medical records is typically protected by legislation although legislation dealing specifically or comprehensively with data privacy may not be in place. Health care provider trust in the privacy of health data at their own facilities is associated with the presence of security safeguards. CONCLUSION: Addressing legal requirements and ensuring that privacy and data security of women's and children's health information is protected is an ethical responsibility that must not be ignored or postponed, particularly where the need is greatest. Not only are the potential harm and unintended consequences of inaction serious for individuals, but they could impact public trust in health registries leading to decreased participation and compromised data integrity. PMID- 27663978 TI - CXCL13 rather than IL-31 is a potential indicator in patients with hepatocellular carcinoma. AB - PURPOSE: To evaluate the expression and role of serum CXC chemokine ligand 13 (CXCL13) and cytokine IL-31 in hepatocellular carcinoma (HCC) patients. METHODS: A case-control study including preoperative serum samples of 78 patients with HCC, 78 patients with chronic hepatitis B (CHB) and 36 healthy controls (HCs) was conducted. The levels of serum CXCL13 and IL-31 were measured by enzyme-linked immunosorbent assays. The correlation of serum cytokines and clinical characteristics, laboratory parameters were analyzed retrospectively. RESULTS: Serum CXCL13, rather than IL-31, was significantly higher in patients with HCC compared with CHB patients or healthy controls. Moreover, there were no statistical differences between CHB patients and healthy controls. Serum CXCL13 was further increased in patients with large tumor size, metastasis and advanced HCC (TNM III-IV Stage). On correlation analysis, the levels of serum CXCL13 were related to HB, ALB, CHE, INR and Child-Pugh scores. The area under the ROC curve values for combination of CXCL13 and AFP was 0.938, whose sensitivity and specificity was 82.8% and 100%, respectively. CONCLUSIONS: This study indicated that CXCL13 rather than IL-31 may have clinical values of diagnosis and prognosis in HCC. PMID- 27663980 TI - Optimizing detection and analysis of slow waves in sleep EEG. AB - BACKGROUND: Analysis of individual slow waves in EEG recording during sleep provides both greater sensitivity and specificity compared to spectral power measures. However, parameters for detection and analysis have not been widely explored and validated. NEW METHOD: We present a new, open-source, Matlab based, toolbox for the automatic detection and analysis of slow waves; with adjustable parameter settings, as well as manual correction and exploration of the results using a multi-faceted visualization tool. RESULTS: We explore a large search space of parameter settings for slow wave detection and measure their effects on a selection of outcome parameters. Every choice of parameter setting had some effect on at least one outcome parameter. In general, the largest effect sizes were found when choosing the EEG reference, type of canonical waveform, and amplitude thresholding. COMPARISON WITH EXISTING METHOD: Previously published methods accurately detect large, global waves but are conservative and miss the detection of smaller amplitude, local slow waves. The toolbox has additional benefits in terms of speed, user-interface, and visualization options to compare and contrast slow waves. CONCLUSIONS: The exploration of parameter settings in the toolbox highlights the importance of careful selection of detection METHODS: The sensitivity and specificity of the automated detection can be improved by manually adding or deleting entire waves and or specific channels using the toolbox visualization functions. The toolbox standardizes the detection procedure, sets the stage for reliable results and comparisons and is easy to use without previous programming experience. PMID- 27663983 TI - The Inherited p53 Mutation in the Brazilian Population. AB - A common criticism of studying rare diseases is the often-limited relevance of the findings to human health. Here, we review ~15 years of research into an unusual germline TP53 mutation (p.R337H) that began with its detection in children with adrenocortical carcinoma (ACC), a remarkably rare childhood cancer that is associated with poor prognosis. We have come to learn that the p.R337H mutation exists at a very high frequency in Southern and Southeastern Brazil, occurring in one of 375 individuals within a total population of ~100 million. Moreover, it has been determined that carriers of this founder mutation display variable tumor susceptibility, ranging from isolated cases of pediatric ACC to Li Fraumeni or Li-Fraumeni-like (LFL) syndromes, thus representing a significant medical issue for this country. Studying the biochemical and molecular consequences of this mutation on p53 tumor-suppressor activity, as well as the putative additional genetic alterations that cooperate with this mutation, is advancing our understanding of how p53 functions in tumor suppression in general. These studies, which originated with a rare childhood tumor, are providing important information for guiding genetic counselors and physicians in treating their patients and are already providing clinical benefit. PMID- 27663985 TI - Workplace bullying and the association with suicidal ideation/thoughts and behaviour: a systematic review. AB - The established links between workplace bullying and poor mental health provide a prima facie reason to expect that workplace bullying increases the risk of suicidal ideation (thoughts) and behaviours. Until now, there has been no systematic summary of the available evidence. This systematic review summarises published studies reporting data on workplace bullying and suicidal ideation, or behaviour. The review sought to ascertain the nature of this association and highlight future research directions. 5 electronic databases were searched. 2 reviewers independently selected the articles for inclusion, and extracted information about study characteristics (sample, recruitment method, assessment and measures) and data reporting the association of workplace bullying with suicidal ideation and behaviour. 12 studies were included in the final review-8 reported estimates of a positive association between workplace bullying and suicidal ideation, and a further 4 provided descriptive information about the prevalence of suicidal ideation in targets of bullying. Only 1 non-representative cross-sectional study examined the association between workplace bullying and suicidal behaviour. The results show an absence of high-quality epidemiological studies (eg, prospective cohort studies, which controlled for workplace characteristics and baseline psychiatric morbidity). While the available literature (predominantly cross-sectional) suggests that there is a positive association between workplace bullying and suicidal ideation, the low quality of studies prevents ruling out alternative explanations. Further longitudinal, population-based research, adjusting for potential covariates (within and outside the workplace), is needed to determine the level of risk that workplace bullying independently contributes to suicidal ideation and behaviour. PMID- 27663984 TI - Comparison of illegal drug use pattern in Taiwan and Korea from 2006 to 2014. AB - BACKGROUND: Illegal drug use has long been a global concern. Taiwan and Korea are geographically adjacent and both countries have experienced the illegal use problems of methamphetamine, a predominant prototype of New Psychoactive Substances (NPS). NPS, a term coined by the United Nations Office on Drugs and Crime (UNODC) in recent years, have not been scrutinized for their safety and may become a new threat to public health and security worldwide. To conduct evidence based drug policy, it is imperative to estimate the trend and pattern of illegal drug use. Therefore, this study aims to analyze and compare the current status of drug-related seizures, arrests and illegal drug use, with a focus on methamphetamine and NPS, between Taiwan and Korea. METHODS: Data of illegal drug (including NPS)-related seizures and arrests were collected via anti-drug related agencies of both countries from 2006 through 2014.Since listing of NPS as controlled substances was a result of NPS abuse liability through official evaluation, the items of controlled NPS were used as an indicator of emerging use. These data obtained from Taiwan and Korea was then compared. RESULTS: The results showed that while methamphetamine remained as a predominant drug in both Taiwan and Korea for decades, different illegal drug use patterns have been observed in these two countries. In Taiwan, the major illegal drugs were methamphetamine, heroin, and ketamine, whereas in Korea those were methamphetamine and cannabis. By comparison of per capita illicit drug seizures, the illegal drug use situation in Taiwan was at a higher stake than that in Korea. In terms of NPS use, ketamine has been a major drug in Taiwan, but it was seldom found in Korea. Besides ketamine, the major type of NPS was synthetic cathinones in Taiwan whereas it was synthetic cannabinoids and phenethylamines in Korea. The difference in the numbers of controlled NPS items between Taiwan (23) and Korea (93) may be due to the implementation of temporary control on NPS in Korea since 2011. CONCLUSION: While the problem of methamphetamine still lingers, NPS have emerged as a new issue in both countries. However, the NPS pattern was different between Taiwan and Korea. Although the controlled NPS items in Taiwan were far less than those in Korea, the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea. Different NPS pattern may also imply they were from different sources. Factors other than geographical proximity, such as drug policy and availability and accessibility to drugs, should be taken into account for the current status of illegal drug use in Korea and Taiwan. PMID- 27663982 TI - Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance. AB - The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp. Newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) were designed in a targeted fashion to increase antibacterial activity, in some cases through secondary mechanisms of action. Resistance to the glycopeptides emerged in delayed fashion and occurs via a spectrum of chromosome- and plasmid-associated elements that lead to structural alteration of the bacterial cell-wall precursor substrates. PMID- 27663981 TI - Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity. AB - Solid tumors consist of cancer cells and stromal cells, including resident and transiting immune cells-all ensconced in an extracellular matrix (ECM)-nourished by blood vessels and drained by lymphatic vessels. The microenvironment constituents are abnormal and heterogeneous in morphology, phenotype, and physiology. Such irregularities include an inefficient tumor vascular network comprised of leaky and compressed vessels, which impair blood flow and oxygen delivery. Low oxygenation in certain tumor regions-or focal hypoxia-is a mediator of cancer progression, metastasis, immunosuppression, and treatment resistance. Thus, repairing an abnormal and heterogeneous microenvironment-and hypoxia in particular-can significantly improve treatments of solid tumors. Here, we summarize two strategies to reengineer the tumor microenvironment (TME)-vessel normalization and decompression-that can alleviate hypoxia. In addition, we discuss how these two strategies alone and in combination with each other-or other therapeutic strategies-may overcome the challenges posed by cancer heterogeneity. PMID- 27663986 TI - Associations among rotating night shift work, sleep and skin cancer in Nurses' Health Study II participants. AB - BACKGROUND: Night shift work and sleep duration have been associated with breast and other cancers. Results from the few prior studies of night shift work and skin cancer risk have been mixed and not fully accounted for other potentially important health-related variables (eg, sleep characteristics). This study evaluated the relationship between rotating night shift work and skin cancer risk and included additional skin cancer risk factors and sleep-related variables. METHODS: The current study used data from 74 323 Nurses' Health Study (NHS) II participants. Cox proportional hazards models were used to estimate multivariable adjusted HRs and 95% CIs for skin cancers across categories of shift work and sleep duration. RESULTS: Over 10 years of follow-up, 4308 basal cell carcinoma (BCC), 334 squamous cell carcinoma (SCC) and 212 melanoma cases were identified. Longer duration of rotating night shifts was associated with a linear decline in risk of BCC (HR=0.93, 95% CI 0.90 to 0.97 per 5-year increase). Shift work was not significantly associated with either melanoma (HR=1.02, 95% CI 0.86 to 1.21) or SCC (HR=0.92, 95% CI 0.80 to 1.06). A short sleep duration (<=6 hours per day) was associated with lower risks of melanoma (HR=0.68, 95% CI 0.46 to 0.98) and BCC (HR=0.93, 95% CI 0.86 to 1.00) compared with the most common report of 7 hours. SCC was not associated with duration of sleep (HR=0.94, 95% CI 0.83 to 1.06). CONCLUSIONS: Longer duration of rotating night shift work and shorter sleep duration were associated with lower risk of some skin cancers. Further research is needed to confirm and identify the mechanisms underlying these associations. PMID- 27663988 TI - Fully-integrated framework for the segmentation and registration of the spinal cord white and gray matter. AB - The spinal cord white and gray matter can be affected by various pathologies such as multiple sclerosis, amyotrophic lateral sclerosis or trauma. Being able to precisely segment the white and gray matter could help with MR image analysis and hence be useful in further understanding these pathologies, and helping with diagnosis/prognosis and drug development. Up to date, white/gray matter segmentation has mostly been done manually, which is time consuming, induces a bias related to the rater and prevents large-scale multi-center studies. Recently, few methods have been proposed to automatically segment the spinal cord white and gray matter. However, no single method exists that combines the following criteria: (i) fully automatic, (ii) works on various MRI contrasts, (iii) robust towards pathology and (iv) freely available and open source. In this study we propose a multi-atlas based method for the segmentation of the spinal cord white and gray matter that addresses the previous limitations. Moreover, to study the spinal cord morphology, atlas-based approaches are increasingly used. These approaches rely on the registration of a spinal cord template to an MR image, however the registration usually doesn't take into account the spinal cord internal structure and thus lacks accuracy. In this study, we propose a new template registration framework that integrates the white and gray matter segmentation to account for the specific gray matter shape of each individual subject. Validation of segmentation was performed in 24 healthy subjects using T2*-weighted images, in 8 healthy subjects using diffusion weighted images (exhibiting inverted white-to-gray matter contrast compared to T2*-weighted), and in 5 patients with spinal cord injury. The template registration was validated in 24 subjects using T2*-weighted data. Results of automatic segmentation on T2* weighted images was in close correspondence with the manual segmentation (Dice coefficient in the white/gray matter of 0.91/0.71 respectively). Similarly, good results were obtained in data with inverted contrast (diffusion-weighted image) and in patients. When compared to the classical template registration framework, the proposed framework that accounts for gray matter shape significantly improved the quality of the registration (comparing Dice coefficient in gray matter: p=9.5*10-6). While further validation is needed to show the benefits of the new registration framework in large cohorts and in a variety of patients, this study provides a fully-integrated tool for quantitative assessment of white/gray matter morphometry and template-based analysis. All the proposed methods are implemented in the Spinal Cord Toolbox (SCT), an open-source software for processing spinal cord multi-parametric MRI data. PMID- 27663987 TI - Decoding information about dynamically occluded objects in visual cortex. AB - During dynamic occlusion, an object passes behind an occluding surface and then later reappears. Even when completely occluded from view, such objects are experienced as continuing to exist or persist behind the occluder even though they are no longer visible. The contents and neural basis of this persistent representation remain poorly understood. Questions remain as to whether there is information maintained about the object itself (i.e. its shape or identity) or non-object-specific information such as its position or velocity as it is tracked behind an occluder, as well as which areas of visual cortex represent such information. Recent studies have found that early visual cortex is activated by "invisible" objects during visual imagery and by unstimulated regions along the path of apparent motion, suggesting that some properties of dynamically occluded objects may also be neurally represented in early visual cortex. We applied functional magnetic resonance imaging in human subjects to examine representations within visual cortex during dynamic occlusion. For gradually occluded, but not for instantly disappearing objects, there was an increase in activity in early visual cortex (V1, V2, and V3). This activity was spatially specific, corresponding to the occluded location in the visual field. However, the activity did not encode enough information about object identity to discriminate between different kinds of occluded objects (circles vs. stars) using MVPA. In contrast, object identity could be decoded in spatially-specific subregions of higher-order, topographically organized areas such as ventral, lateral, and temporal occipital areas (VO, LO, and TO) as well as the functionally defined LOC and hMT+. These results suggest that early visual cortex may only represent the dynamically occluded object's position or motion path, while later visual areas represent object-specific information. PMID- 27663989 TI - Whole brain MP2RAGE-based mapping of the longitudinal relaxation time at 9.4T. AB - Mapping of the longitudinal relaxation time (T1) with high accuracy and precision is central for neuroscientific and clinical research, since it opens up the possibility to obtain accurate brain tissue segmentation and gain myelin-related information. An ideal, quantitative method should enable whole brain coverage within a limited scan time yet allow for detailed sampling with sub-millimeter voxel sizes. The use of ultra-high magnetic fields is well suited for this purpose, however the inhomogeneous transmit field potentially hampers its use. In the present work, we conducted whole brain T1 mapping based on the MP2RAGE sequence at 9.4T and explored potential pitfalls for automated tissue classification compared with 3T. Data accuracy and T2-dependent variation of the adiabatic inversion efficiency were investigated by single slice T1 mapping with inversion recovery EPI measurements, quantitative T2 mapping using multi-echo techniques and simulations of the Bloch equations. We found that the prominent spatial variation of the transmit field at 9.4T (yielding flip angles between 20% and 180% of nominal values) profoundly affected the result of image segmentation and T1 mapping. These effects could be mitigated by correcting for both flip angle and inversion efficiency deviations. Based on the corrected T1 maps, new, 'flattened', MP2RAGE contrast images were generated, that were no longer affected by variations of the transmit field. Unlike the uncorrected MP2RAGE contrast images acquired at 9.4T, these flattened images yielded image segmentations comparable to 3T, making bias-field correction prior to image segmentation and tissue classification unnecessary. In terms of the T1 estimates at high field, the proposed correction methods resulted in an improved precision, with test retest variability below 1% and a coefficient-of-variation across 25 subjects below 3%. PMID- 27663993 TI - Attachment, Development, and Mental Health in Abused and Neglected Preschool Children in Foster Care: A Meta-Analysis. AB - A proper preparation for foster parents to care for abused and neglected children includes effective training and initial diagnostics in order to plan individual treatment. Hence, a basic knowledge about the main psychosocial and developmental problems associated with abuse and neglect and their prevalence in foster children is needed. For this purpose, a systematical literature review and a series of meta-analyses were conducted. A total of 25 studies reporting data on development ( n = 4,033), mental health ( n = 726), and attachment ( n = 255) of foster children in preschool age met the inclusion criteria. The meta-analyses indicated prevalence rates of approximately 40% for developmental, mental health problems, and insecure attachment. Rates of disorganized attachment were estimated to 22%. These findings outline the necessity of an initial trauma oriented diagnostics and trainings for foster parents that address foster children's development, mental health, and disorganized attachment. PMID- 27663992 TI - Searching for better animal models of BPD: a perspective. AB - There have been many efforts to develop good animal models of bronchopulmonary dysplasia (BPD) to better understand the pathophysiology and mechanisms underlying development of BPD as well as to test potential strategies for its prevention and treatment. This Perspectives summarizes the features of common animal models of BPD and the strengths and limitations of such models. Potential optimal approaches to development of animal models are indicated, with the underlying concepts that require emphasis. PMID- 27663991 TI - Correction of lung inflammation in a F508del CFTR murine cystic fibrosis model by the sphingosine-1-phosphate lyase inhibitor LX2931. AB - Progressive lung disease with early onset is the main cause of mortality and morbidity in cystic fibrosis patients. Here we report a reduction of sphingosine 1-phosphate (S1P) in the lung of unchallenged Cftrtm1EUR F508del CFTR mutant mice. This correlates with enhanced infiltration by inducible nitric oxide synthase (iNOS)-expressing granulocytes, B cells, and T cells. Furthermore, the ratio of macrophage-derived dendritic cells (MoDC) to conventional dendritic cells (cDC) is higher in mutant mouse lung, consistent with unprovoked inflammation. Oral application of a S1P lyase inhibitor (LX2931) increases S1P levels in mutant mouse tissues. This normalizes the lung MoDC/cDC ratio and reduces B and T cell counts. Lung granulocytes are enhanced, but iNOS expression is reduced in this population. Although lung LyC6+ monocytes are enhanced by LX2931, they apparently do not differentiate to MoDC and macrophages. After challenge with bacterial toxins (LPS-fMLP) we observe enhanced levels of proinflammatory cytokines TNF-alpha, KC, IFNgamma, and IL-12 and the inducible mucin MUC5AC in mutant mouse lung, evidence of deficient resolution of inflammation. LX2931 does not prevent transient inflammation or goblet cell hyperplasia after challenge, but it reduces MUC5AC and proinflammatory cytokine levels toward normal values. We conclude that lung pathology in homozygous mice expressing murine F508del CFTR, which represents the most frequent mutation in CF patients, is characterized by abnormal behavior of infiltrating myeloid cells and delayed resolution of induced inflammation. This phenotype can be partially corrected by a S1P lyase inhibitor, providing a rationale for therapeutic targeting of the S1P signaling pathway in CF patients. PMID- 27663994 TI - Stereodynamics of some pyridoxine derivatives. AB - The conformational properties of three pyridoxine derivatives were studied by 1 H dynamic NMR spectroscopy. Conformational exchange caused by a rotation of 2 nytrophenyl group around one single C-C bond, of 2,4-dinitrophenyl substituent around two single C-O bonds, and twist-twist transformations of the seven membered ketal cycle was observed by NMR experiments at low temperatures. Meanwhile, the conformational exchange of the acetal ring remains fast in the NMR timescale even at 198 K. The energy barriers for all observed conformational exchange processes were determined by the lineshape analysis of dynamic NMR spectra. The activation barriers of the 2-nitrophenyl group rotation were almost the same for all studied compounds, about 40-41 kJ/mol. The energy barriers of the conformational exchange processes of the 2,4-nitrophenyl group and the ketal cycle increased significantly up to 10 kJ/mol in comparison with previously studied compounds with similar structure. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27663995 TI - A web-based group course intervention for 15-25-year-olds whose parents have substance use problems or mental illness: study protocol for a randomized controlled trial. AB - BACKGROUND: Depending on the definitions used, between 5 and 20 % of all Swedish children grow up with at least one parent suffering from alcohol problems, while 6 % have at least one parent who has received inpatient psychiatric care, conditions that may affect the children negatively. Nine out of ten Swedish municipalities therefore provide support resources, but less than 2 % of these children are reached by such support. Delivering intervention programs via the Internet is a promising strategy. However, web-based programs targeting this at risk group of children are scarce. We have previously developed a 1.5-h-long web based self-help program, Alcohol & Coping, which appears to be effective with regards to adolescents' own alcohol consumption. However, there is a need for a more intense program, and therefore we adapted Kopstoring, a comprehensive Dutch web-based psycho-educative prevention program, to fit the Swedish context. The purpose of the program, which in Swedish has been called Grubbel, is to strengthen protective factors, such as coping skills and psychological well being, prevent the development of psychological disorders, and reduce alcohol consumption. METHODS/DESIGN: The aim of the current study is to evaluate the effectiveness of Grubbel, which targets 15-25-year-olds whose parents have substance use problems and/or mental illness. Specific research questions relate to the participants' own coping strategies, mental health status and substance use. The study was initiated in the spring of 2016 and uses a two-armed RCT design. Participants will be recruited via social media and also through existing agencies that provide support to this target group. The assessment will consist of a baseline measurement (t0) and three follow-ups after six (t1), 12 (t2), and 24 months (t3). Measures include YSR, CES-DC, Ladder of Life, Brief COPE, AUDIT C, and WHOQOL-BREF. DISCUSSION: Studies have revealed that the majority of children whose parents have substance use or mental health problems are not reached by the existing support. Thus, there is an urgent need to develop, implement, and evaluate novel intervention programs and disseminate successful programs to a broader audience. This study, investigating the effects of a web based intervention, therefore makes an important contribution to this field of research. TRIAL REGISTRATION: ISRCTN10099247 . Retrospectively registered on August 31, 2016. PMID- 27663996 TI - Skin metastases of cervical cancer: two case reports and review of the literature. AB - BACKGROUND: Although cervix carcinoma is one of the most common malignancies in women, hematogenous metastases are relatively not common. Cutaneous metastases, in particular, are unusual even at an advanced stage of disease. Their presence is a predictor of poor prognosis. CASE PRESENTATION: Case 1: A 63-year-old postmenopausal Moroccan woman was diagnosed as having cervical squamous cell carcinoma. She was treated with radical concurrent chemotherapy and radiation therapy followed by low-dose brachytherapy. Six months after finishing the therapy, multiple skin nodules appeared on her abdomen and chest wall. An excision biopsy was performed and showed metastatic squamous cell carcinoma. Her disease progressed and she died before completing her fourth course of palliative chemotherapy. Case 2: A 48-year-old Moroccan woman was diagnosed as having cervical squamous cell carcinoma; she was treated with concurrent chemoradiation. Before a planned high-dose brachytherapy, she noticed many nodular lesions on her arms, thighs, and chest wall. An excision biopsy was performed and showed metastatic squamous cell carcinoma. She then underwent a series of imaging examinations, including computed tomography of her chest, abdomen, and pelvis, and a whole body bone scan that showed disseminated disease involving her lungs and bones. She died after two courses of palliative chemotherapy, 2 months after the appearance of the skin lesions. CONCLUSION: We report two cases to illustrate a rare localization of metastasis from cervical carcinoma that is highly aggressive requiring early detection and aggressive management. PMID- 27663997 TI - Bile duct adenoma in patient with chronic hepatitis C: As a benign neoplasm by pathological and imaging studies. PMID- 27663990 TI - Regulation of pulmonary endothelial barrier function by kinases. AB - The pulmonary endothelium is the target of continuous physiological and pathological stimuli that affect its crucial barrier function. The regulation, defense, and repair of endothelial barrier function require complex biochemical processes. This review examines the role of endothelial phosphorylating enzymes, kinases, a class with profound, interdigitating influences on endothelial permeability and lung function. PMID- 27663998 TI - Response on 'comparing concentration-based (AOT40) and stomatal uptake (PODY) metrics for ozone risk assessment to European forests'. PMID- 27664000 TI - Dementia strategy has not cut antipsychotic prescribing in care homes, study finds. PMID- 27663999 TI - Bibliometric analysis of global scientific research on carbapenem resistance (1986-2015). AB - BACKGROUND: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat. This study was carried out to give a bibliometric overview of literature on carbapenem resistance. In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed. METHODS: Specific keywords pertaining to carbapenem resistance were used in Scopus database. Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps. RESULTS: A total of 2617 journal articles were retrieved. The average number of citations per article was of 21.47. The growth of publications showed a dramatic increase from 2008 to 2015. Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by 102 different countries. The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When productivity was stratified by population size, Greece ranked first followed by France. Greece also ranked first when data were stratified by gross domestic product (GDP). Asian countries have lesser international collaboration compared with other countries in the top ten list. Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea). Other active institutes included an Israeli and a Brazilian institute. Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases. CONCLUSION: There was a dramatic increase in number of publications on carbapenem resistance in the past few years. These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America. International collaboration needs to be encouraged particularly for researchers in Asia. Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance. This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance. PMID- 27664001 TI - Comparative Human Health Impact Assessment of Engineered Nanomaterials in the Framework of Life Cycle Assessment. AB - For safe innovation, knowledge on potential human health impacts is essential. Ideally, these impacts are considered within a larger life-cycle-based context to support sustainable development of new applications and products. A methodological framework that accounts for human health impacts caused by inhalation of engineered nanomaterials (ENMs) in an indoor air environment has been previously developed. The objectives of this study are as follows: (i) evaluate the feasibility of applying the CF framework for NP exposure in the workplace based on currently available data; and (ii) supplement any resulting knowledge gaps with methods and data from the life cycle approach and human risk assessment (LICARA) project to develop a modified case-specific version of the framework that will enable near-term inclusion of NP human health impacts in life cycle assessment (LCA) using a case study involving nanoscale titanium dioxide (nanoTiO2 ). The intent is to enhance typical LCA with elements of regulatory risk assessment, including its more detailed measure of uncertainty. The proof-of principle demonstration of the framework highlighted the lack of available data for both the workplace emissions and human health effects of ENMs that is needed to calculate generalizable characterization factors using common human health impact assessment practices in LCA. The alternative approach of using intake fractions derived from workplace air concentration measurements and effect factors based on best-available toxicity data supported the current case-by-case approach for assessing the human health life cycle impacts of ENMs. Ultimately, the proposed framework and calculations demonstrate the potential utility of integrating elements of risk assessment with LCA for ENMs once the data are available. PMID- 27664002 TI - Stop vasodepressor drugs in reflex syncope: a randomised controlled trial. AB - OBJECTIVES: Most elderly patients affected by reflex vasodepressor syncope take one or more hypotensive drugs. The role of these drugs in causing syncope has not yet been established. We hypothesised that recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy without increasing the risk of cardiovascular and neurological events. METHODS: This randomised, parallel, prospective, trial was conducted from January 2014 to March 2016 in four general hospitals. Of 328 initially screened participants, 58 patients (mean (SD) age 74+/-11 years) affected by vasodepressor reflex syncope, which was reproduced by tilt testing (n=54) or carotid sinus massage (n=4), were randomised to stop/reduce vasoactive therapy or to continue it. Primary end point was recurrence of syncope, presyncope or adverse events (defined as stroke, cerebral transient ischaemic attacks, worsening heart failure, myocardial infarction). RESULTS: Of 58 patients who were randomised, 55 completed the trial. After 1 month, systolic blood pressure was significantly higher in the 'stop/reduce' group than in the 'continue' group, in both supine (141+/-13 mm Hg vs 128+/-14 mm Hg; p=0.004) and standing (133+/-13 mm Hg vs 122+/-15 mm Hg; p=0.02) positions. During a mean follow-up of 13+/-7 months, the primary combined end point occurred in seven 'stop/reduce' patients (23%): three had syncope, three had presyncope and one had heart failure. Conversely, it occurred in 13 'continue' patients (54%): 10 had syncope, 2 had presyncope and 1 had cerebral transient ischaemic attack. The log-rank p value was 0.02 and the HR was 0.37 (95% CI 0.15 to 0.91). CONCLUSIONS: Recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy in most elderly patients affected by reflex vasodepressor syncope. TRIAL REGISTRATION NUMBER: NCT01509534; EudraCT2013 004364-63; Results. PMID- 27664003 TI - Early surgery versus watchful waiting for asymptomatic severe aortic valve stenosis: a hot topic for the past 20 years. PMID- 27664004 TI - 77-year-old female with syncope. AB - CLINICAL INTRODUCTION: A 77-year-old female was referred for evaluation of an episode of syncope while eating breakfast. There was no history of fall, syncope, prodrome, dyspnoea, chest discomfort or palpitations. Medical history was notable for hyperlipidaemia and treated hypertension. Blood pressure was 140/90 mm Hg, pulse 85 beats per minute (BPM). No murmurs were present on cardiac examination. ECG revealed normal sinus rhythm with left ventricular (LV) hypertrophy (see online supplementary figure S1). Holter monitor demonstrated rare premature ventricular complexes (<1% of beats), without heart block or ventricular tachycardia. Transthoracic echocardiogram is shown in figure 1. QUESTION: Which of the following is the explanation for the flow indicated by the yellow arrow? Aortic stenosisCoronary artery flow, indicative of coronary fistulaHypertrophic cardiomyopathy with apical pouchHypertensive heart diseaseMitral stenosis. PMID- 27664005 TI - Is long-standing pulmonary regurgitation that deleterious? Some lessons from the past. PMID- 27664006 TI - Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice. AB - Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor MEK expression. The suitable dosage and supplementation periods of choline await further exploration. PMID- 27664008 TI - Dietary flavonoid derivatives enhance chemotherapeutic effect by inhibiting the DNA damage response pathway. AB - Flavonoids are the most common group of polyphenolic compounds and abundant in dietary fruits and vegetables. Diet high in vegetables or dietary flavonoid supplements is associated with reduced mortality rate for patients with breast cancer. Many studies have been proposed for mechanisms linking flavonoids to improving chemotherapy efficacy in many types of cancers, but data on this issue is still limited. Herein, we report on a new mechanism through which dietary flavonoids inhibit DNA damage checkpoints and repair pathways. We found that dietary flavonoids could inhibit Chk1 phosphorylation and decrease clonogenic cell growth once breast cancer cells receive ultraviolet irradiation, cisplatin, or etoposide treatment. Since the ATR-Chk1 pathway mainly involves response to DNA replication stress, we propose that flavonoid derivatives reduce the side effect of chemotherapy by improving the sensitivity of cycling cells. Therefore, we propose that increasing intake of common dietary flavonoids is beneficial to breast cancer patients who are receiving DNA-damaging chemotherapy, such as cisplatin or etoposide-based therapy. PMID- 27664009 TI - Offspring Socioeconomic Status and Parent Mortality Within a Historical Population. AB - Considering a network approach to health determinants, we test the hypothesis that benefits of high socioeconomic status (SES) may be transmitted up the generational ladder from offspring to parents. Studies that examine own SES and own health outcomes, or SES of parents and outcomes of young or adolescent children, are common. Those that investigate SES of offspring and their association with parental health are rare. Employing data from a historical population of individuals extracted from a comprehensive population database that links demographic and vital records across generations, this study tests the hypothesis that higher offspring SES associates with lower parental mortality after controlling for parental SES. The sample includes 29,972 individuals born between 1864 and 1883 whose offspring were born between 1886 and 1920. SES is operationalized using Nam-Powers occupational status scores divided into quartiles and a category for farmers. Models assess mortality risk after age 40. Included is a test for whether effects are proportional across parents who died younger and older. Estimated life expectancies across categories of offspring SES conditioned on parental SES are calculated to illustrate specifically how differences in SES relate to differences in years lived. Results indicate a longevity penalty for those whose offspring have low SES and a longevity dividend for those with high-SES offspring. The influence of offspring attributes on well being of parents points to fluid and myriad linkages between generations. PMID- 27664007 TI - Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells. AB - Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. PMID- 27664010 TI - Response of anodic bacterial community to the polarity inversion for chloramphenicol reduction. AB - Chloramphenicol (CAP) is a frequently detected environmental pollutant. In this study, an electroactive biofilm for CAP reduction was established by initially in the anode and then inverting to the cathode. The established biocathode could enhance the reduction of CAP to the nitro-group reduced CAP (AMCl2) and further dechlorinated form (AMCl), both had lost the antibacterial activity. The phylogenetic diversity of the acclimated biofilm was decreased after the polar inversion. Proportions of functional bacterial genera, including Geobacter, Desulfovibrio and Pseudomonas responsible for the bidirectional electron transfer and nitroaromatics reduction, had increased 28%, 104% and 43% in the cathode. The relatively high abundances (over 50%) of Geobacter in anode and cathode were rarely detected for the nitroaromatics reduction. This study provides new insights into the electroactive biofilm structure improvement by the polarity inversion strategy for refractory antibiotics degradation. PMID- 27664013 TI - Suicidal Behavior Among People Living with HIV (PLHIV) in Medical Care in Estonia and Factors Associated with Receiving Psychological Treatment. AB - People living with HIV (PLHIV) have higher rates of suicidal behavior than the general population. This study assessed suicidal behavior (ideation and/or attempts, ever and in the past 12 months) among PLHIV receiving outpatient HIV medical care in Estonia and associations between suicidal behavior and psychological treatment. The cross-sectional study collected data from January to November 2013 using a self-report questionnaire. Eight hundred PLHIV participated, 39 % (n = 306) of whom had been suicidal. Lifetime prevalence was 36 % for suicidal ideation and 20 % for attempts. Younger age, incarceration, having ever abused alcohol and also injected drugs, having lived with HIV for more than 10 years, and being depressed were associated with lifetime suicidal behavior. Suicidal behavior within the past 12 months was reported by 20 % (n = 156) of respondents. Of these, 27 % received psychological treatment (counseling and/or psychotherapy), 20 % had taken antidepressants, and 49 % sedatives. Individuals perceiving a need for treatment were significantly more likely to receive psychological treatment when experiencing suicidal behavior (OR 25.65, 95 % CI 2.92-225.47). In conclusion, suicidal behavior is frequent among PLHIV but psychological treatment is not often received. One of the barriers to treatment is patients' lack of perceived need for help. PMID- 27664012 TI - Prostaglandin D2 effects and DP1 /DP2 receptor distribution in guinea pig urinary bladder out-flow region. AB - The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD2 actions in guinea pig out-flow region and the distribution of DP1 /DP2 receptors. The effects of PGD2 on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP1 /DP2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP1 /DP2 receptors. PGD2 in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD2 was equally (trigone) or slightly less potent (urethra) compared with PGE2 . Expression of DP1 and DP2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP1 and DP2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD2 may therefore be a modulator of the bladder out-flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome. PMID- 27664011 TI - Mutant IDH1 and thrombosis in gliomas. AB - Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2 hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE. PMID- 27664014 TI - Regulation of Soluble Phosphate on the Ability of Phytate Mineralization and beta Propeller Phytase Gene Expression of Pseudomonas fluorescens JZ-DZ1, a Phytate Mineralizing Rhizobacterium. AB - Phytate-mineralizing rhizobacteria (PMR) play an important role in providing phosphorus for the sustainable plant growth. It is important to investigate the ability of PMR to produce phytase under different phosphate levels for its application. The effects of different concentrations of soluble phosphate on the ability of phytate mineralization of Pseudomonas fluorescens JZ-DZ1, a phytate mineralizing rhizobacterium, were investigated in both solid and liquid media. The results on solid media showed that halo zone width gradually reduced with concentrations of soluble phosphate increasing from 0.05 to 20 mM, indicating the reduction of the ability of phytate mineralization. The results were consistent with the quantitative detection of phytase activity from the overall trend. An 1866-bp beta-propeller phytase (BPP) gene (phyPf) was cloned from the strain, and the deduced amino acid sequence of phyPf shared 98 % of identity with a known BPP from Pseudomonas sp. BS10-3 (AJF36073.1). The results of relative real-time quantitative PCR assay showed that the expression of phyPf was induced by a low concentration (0.1 mM) of soluble phosphate, suggesting that BPP secretion was regulated by gene phyPf. The BPP-harboring bacterium P. fluorescens JZ-DZ1 with low phosphate-inducible ability of phytate mineralization could be potentially applied to promote phosphorus uptake for plants in the future. PMID- 27664016 TI - Plant Cell Imaging Based on Nanodiamonds with Excitation-Dependent Fluorescence. AB - Despite extensive work on fluorescence behavior stemming from color centers of diamond, reports on the excitation-dependent fluorescence of nanodiamonds (NDs) with a large-scale redshift from 400 to 620 nm under different excitation wavelengths are so far much fewer, especially in biological applications. The fluorescence can be attributed to the combined effects of the fraction of sp(2) hybridized carbon atoms among the surface of the fine diamond nanoparticles and the defect energy trapping states on the surface of the diamond. The excitation dependent fluorescent NDs have been applied in plant cell imaging for the first time. The results reported in this paper may provide a promising route to multiple-color bioimaging using NDs. PMID- 27664017 TI - Fabrication of Continuous Microfibers Containing Magnetic Nanoparticles by a Facile Magneto-Mechanical Drawing. AB - A facile method termed magneto-mechanical drawing is used to produce polymer composite microfibers. Compared with electrospinning and other fiber spinning methods, magneto-mechanical drawing uses magnetic force generated by a permanent magnet to draw droplets of polymer/magnetic nanoparticle suspensions, leading to fabrication of composite microfibers. In addition, because of the rotating collector, it is easy to control the fiber assembly such as fibrous array in parallel or crossed fibrous structure. The general applicability of this method has also been proved by spinning different polymers and magnetic nanoparticles. The resultant fibers exhibit good superparamagnetic behavior at room temperature and ultrahigh stretchability (~443.8 %). The results indicate that magneto mechanical drawing is a promising technique to fabricate magnetic and stretchable microfibers and devices. PMID- 27664015 TI - Deletion of pilA, a Minor Pilin-Like Gene, from Xanthomonas citri subsp. citri Influences Bacterial Physiology and Pathogenesis. AB - Type IV pili (Tfp) are widely distributed adhesins of bacterial surfaces. In plant pathogenic bacteria, Tfp are involved in host colonization and pathogenesis. Xanthomonas citri subsp. citri (Xcc) is the phytopathogen responsible for citrus canker disease. In this work, three Tfp structural genes, fimA, fimA1, and pilA from Xcc were studied. A pilA mutant strain from Xcc (XccDeltapilA) was constructed and differences in physiological features, such as motilities, adhesion, and biofilm formation, were observed. A structural study of the purified Tfp fractions from Xcc wild-type and Xcc?pilA showed that pilins are glycosylated in both strains and that FimA and FimA1 are the main structural components of the pili. Furthermore, smaller lesion symptoms and reduced bacterial growth were produced by Xcc?pilA in orange plants compared to the wild type strain. These results indicate that the minor pilin-like gene, pilA, is involved in Tfp performance during the infection process. PMID- 27664018 TI - A Nanofluidic Biosensor Based on Nanoreplica Molding Photonic Crystal. AB - A nanofluidic biosensor based on nanoreplica molding photonic crystal (PC) was proposed. UV epoxy PC was fabricated by nanoreplica molding on a master PC wafer. The nanochannels were sealed between the gratings on the PC surface and a taped layer. The resonance wavelength of PC-based nanofluidic biosensor was used for testing the sealing effect. According to the peak wavelength value of the sensor, an initial label-free experiment was realized with R6g as the analyte. When the PC-based biosensor was illuminated by a monochromatic light source with a specific angle, the resonance wavelength of the sensor will match with the light source and amplified the electromagnetic field. The amplified electromagnetic field was used to enhance the fluorescence excitation result. The enhancement effect was used for enhancing fluorescence excitation and emission when matched with the resonance condition. Alexa Fluor 635 was used as the target dye excited by 637-nm laser source on a configured photonic crystal enhanced fluorescence (PCEF) setup, and an initial PCEF enhancement factor was obtained. PMID- 27664019 TI - Restricted vs. unrestricted wheel running in mice: Effects on brain, behavior and endocannabinoids. AB - Beneficial effects of voluntary wheel running on hippocampal neurogenesis, morphology and hippocampal-dependent behavior have widely been studied in rodents, but also serious side effects and similarities to stereotypy have been reported. Some mouse strains run excessively when equipped with running wheels, complicating the comparability to human exercise regimes. Here, we investigated how exercise restriction to 6h/day affects hippocampal morphology and metabolism, stereotypic and basal behaviors, as well as the endocannabinoid system in wheel running C57BL/6 mice; the strain most commonly used for behavioral analyses and psychiatric disease models. Restricted and unrestricted wheel running had similar effects on immature hippocampal neuron numbers, thermoregulatory nest building and basal home-cage behaviors. Surprisingly, hippocampal gray matter volume, assessed with magnetic resonance (MR) imaging at 9.4 Tesla, was only increased in unrestricted but not in restricted runners. Moreover, unrestricted runners showed less stereotypic behavior than restricted runners did. However, after blockage of running wheels for 24h stereotypic behavior also increased in unrestricted runners, arguing against a long-term effect of wheel running on stereotypic behavior. Stereotypic behaviors correlated with frontal glutamate and glucose levels assessed by 1H-MR spectroscopy. While acute running increased plasma levels of the endocannabinoid anandamide in former studies in mice and humans, we found an inverse correlation of anandamide with the daily running distance after long-term running. In conclusion, although there are some diverging effects of restricted and unrestricted running on brain and behavior, restricted running does not per se seem to be a better animal model for aerobic exercise in mice. PMID- 27664020 TI - Moderately degenerated lumbar motion segments: Are they truly unstable? AB - The two main load bearing tissues of the intervertebral disc are the nucleus pulposus and the annulus fibrosus. Both tissues are composed of the same basic components, but differ in their organization and relative amounts. With degeneration, the clear distinction between the two tissues disappears. The changes in biochemical content lead to changes in mechanical behaviour of the intervertebral disc. The aim of the current study was to investigate if well documented moderate degeneration at the biochemical and fibre structure level leads to instability of the lumbar spine. By taking into account biochemical and ultrastructural changes to the extracellular matrix of degenerating discs, a set of constitutive material parameters were determined that described the individual tissue behaviour. These tissue biomechanical models were then used to simulate dynamic behaviour of the degenerated spinal motion segment, which showed instability in axial rotation, while a stabilizing effect in the other two principle bending directions. When a shear load was applied to the degenerated spinal motion segment, no sign of instability was found. This study found that reported changes to the nucleus pulposus and annulus fibrosus matrix during moderate degeneration lead to a more stable spinal motion segment and that such biomechanical considerations should be incorporated into the general pathophysiological understanding of disc degeneration and how its progress could affect low back pain and its treatments thereof. PMID- 27664021 TI - Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings. AB - OBJECTIVE: To examine the effects of phentermine combined with a meal replacement program on weight loss and food cravings and to investigate the relationship between food cravings and weight loss. METHODS: In a 12-week randomized, double blind, placebo-controlled clinical trial, 77 adults with obesity received either phentermine or placebo. All participants were provided Medifast(r) meal replacements, were instructed to follow the Take Shape for Life(r) Optimal Weight 5&1 Plan for weight loss, and received lifestyle coaching in the Habits of Health program. The Food Craving Inventory and the General Food Cravings State and Trait Questionnaires were used to measure food cravings. RESULTS: The phentermine group lost 12.1% of baseline body weight compared with 8.8% in the placebo group. Cravings for all food groups decreased in both groups; however, there was a greater reduction in cravings for fats and sweets in the phentermine group compared with the placebo group. Percent weight loss correlated significantly with reduced total food cravings (r = 0.332, P = 0.009), cravings for sweets (r = 0.412, P < 0.000), and state food cravings (r = 0.320, P = 0.007). CONCLUSIONS: Both phentermine combined with a meal replacement program and meal replacements alone significantly reduced body weight and food cravings; however, the addition of phentermine enhanced these effects. PMID- 27664023 TI - Extended wear therapeutic contact lens fabricated from timolol imprinted carboxymethyl chitosan-g-hydroxy ethyl methacrylate-g-poly acrylamide as a onetime medication for glaucoma. AB - An extended wear therapeutic contact lens (TCL) for the sustained delivery of timolol maleate (TML) was fabricated based on molecular imprinting technique. The designed TCL comprised of a TML imprinted copolymer of carboxymethyl chitosan-g hydroxy ethyl methacrylate-g-polyacrylamide (CmCS-g-HEMA-g-pAAm) embedded onto a poly HEMA matrix (pHEMA). Successful reloading of TML onto the lens was monitored using a simple and novel UV-Visible spectrophotometric method which showed an excellent reloading capacity of 6.53MUgTML/TCL. The in vitro drug release profile in lacrimal fluid after each cycle was fitted onto Higuchi model of drug release suggesting diffusion release mechanism with no polymer degradation. Also, the TML release kinetics indicated a sustained drug delivery which can effectively achieve the therapeutic index of TML leading to a onetime medication for glaucoma. Biological activity of eluted drug after each cycle and cell viability of the TCL were verified using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,3-bis(2 methoxynitro-5-sulfophenyl)-5-(phenylaminocarbonyl)-2H-tetrazolium hydroxide (XTT) assay, respectively. PMID- 27664022 TI - Different effects of blue and red light-emitting diodes on antioxidant responses in the liver and ovary of zebrafish Danio rerio. AB - The present study assessed the effects of a white fluorescent bulb (the control) and two different light-emitting diodes (blue LEDs, LDB; red, LDR) on growth, morphology, and oxidative stress in the liver and ovary of zebrafish for 5 weeks. Growth maintained relatively constant under LDB condition, but was reduced under LDR condition. In the liver, hepatosomatic index (HSI) and protein carbonylation (PC) increased under LDR condition, whereas lipid peroxidation (LPO) declined and HSI remained unchanged under LDB condition. The decrease in oxidative damage by LDB could be attributed to the up-regulated levels of mRNA, protein, and activity of Cu/Zn-SOD and CAT. A failure to activate the activity of both enzymes may result in the enhanced PC levels under LDR condition, though both genes were up regulated at transcriptional and translational levels. In the ovary, although gonadosomatic index sharply increased under LDR condition, LPO and PC dramatically accumulated. The increase in oxidative damage by LDR might result from the down-regulated levels of protein and activity of Cu/Zn-SOD and CAT, though both genes were up-regulated at a transcriptional level. Furthermore, a sharp increase in expression of transcription factor Nrf2 that targets antioxidant genes was observed in the liver but not in the ovary under LDB and LDR conditions. In conclusion, our data demonstrated a positive effect of LDB and negative effect of LDR on fish antioxidant defenses, emphasizing the potentials of LDB as an effective light source in fish farming. PMID- 27664024 TI - Freezing and glass transitions upon cooling and warming and ice/freeze concentration-solution morphology of emulsified aqueous citric acid. AB - Although freeze-induced phase separation and the ice/FCS (freeze-concentration solution) morphology of aqueous solutions play an important role in fields ranging from life sciences and biotechnology to geophysics and high-altitude ice clouds, their understanding is far from complete. Herein, using differential scanning calorimetry (DSC) and optical cryo-microscope (OC-M), we have studied the freezing and glass transition behavior and the ice/FCS morphology of emulsified 10-60wt% CA (citric acid) solutions in the temperature region of ~308and153K. We have obtained a lot of new result which are understandable and unclear. The most essential understandable results are as follows: (i) similar to bulk CA/H2O, emulsified CA/H2O also freezes upon cooling and warming and (ii) the ice/FCS morphology of frozen drops smaller than ~3-4MUm is less ramified than that of frozen bulk solutions. Unclear results, among others, are as follows: (i) in contrast to bulk solutions, which produce one freezing event, emulsified CA/H2O produces two freezing events and (ii) in emulsions, drop concentration is not uniform. Our results demonstrate that DSC thermograms and OC-M images/movies are mutually supplementary and allow us to extract important information which cannot be gained when DSC and OC-M techniques are used alone. PMID- 27664025 TI - If We Would Only Ask: How Henrietta Lacks Continues to Teach Us About Perceptions of Research and Genetic Research Among African Americans Today. AB - BACKGROUND: African Americans are under-represented in research, and there are perceptions of unwillingness among African Americans to participate in research. We explored barriers to African American research participation. METHODS: We conducted a cross-sectional survey to explore knowledge and beliefs regarding medical and genetic research among adults (n = 169) at urban community events. Descriptive data were summarized by frequencies for survey responses. RESULTS: Only 13 % of respondents had ever been approached for research; 93 % of those who had been approached for research had participated. Eighty-six percent of those who had previous research experience indicated willingness to participate again vs. only 30 % among those with no research experience. Seventy-four percent had altruistic views of research; 28 % were concerned about truthfulness of researchers; 52 % feared incidental discoveries. CONCLUSION: African Americans have favorable views of research; however, few are being engaged in studies. Effective interventions to address identified barriers may improve participation and lead to better health outcomes among African Americans. PMID- 27664026 TI - Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012. The largest known outbreak outside the Middle East occurred in South Korea in 2015. As of 29 June 2016, 1769 laboratory-confirmed cases (630 deaths; 35.6 % case fatality rate [CFR]) had been reported from 26 countries, particularly in the Middle East. However, the CFR for hospital outbreaks was higher than that of family clusters in the Middle East and Korea. Here, we compared the mortality rates for 51 nosocomial outbreaks in the Middle East and one outbreak of MERS-CoV in South Korea. Our findings showed the CFR in the Middle East was much higher than that in South Korea (25.9 % [56/216] vs. 13.8 % [24/174], p = 0.003). Infected individuals who died were, on average, older than those who survived in both the Middle East (64 years [25-98] vs. 46 years [2-85], p = 0.000) and South Korea (68 years [49-82] vs. 53.5 years [16-87], p = 0.000). Similarly, the co morbidity rates for the fatal cases were statistically higher than for the nonfatal cases in both the Middle East (64.3 % [36/56] vs. 28.1 % [45/160], p = 0.000) and South Korea (45.8 % [11/24] vs. 12.0 % [18/150], p = 0.000). The median number of days from onset to confirmation of infection in the fatal cases was longer than that for survivors from the Middle East (8 days [1-47] vs. 4 days [0-14], p = 0.009). Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. PMID- 27664027 TI - G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the expression of proinflammatory cytokines in mice. AB - Nonstructural protein 1 (NS1) is a multifunctional protein that is a viral replication enhancer and virulence factor. In this study, we investigated the effect of the amino acid substitution G45R on the NS1 of A/Puerto Rico/8/1934 (H1N1) (G45R/NS1) on viral virulence and host gene expression in a mouse model and the human lung cell line A549. The G45R/NS1 virus had increased virulence by inducing an earlier and robust proinflammatory cytokine response in mice. Mice infected with the G45R/NS1 virus lost more body weight and had lower survival rates than mice infected with the wild type (WT/NS1) virus. Replication of the G45R/NS1 virus was higher than that of the WT/NS1 virus in vitro, but the replication of both viruses was similar in mouse lungs. In A549 cells, the majority of G45R/NS1 protein was localized in the cytoplasm whereas the majority of WT/NS1 protein was localized in the nucleus. Microarray analysis revealed that A549 cells infected with the G45R/NS1 virus had higher expression of genes encoding proteins associated with the innate immune response and cytokine activity than cells infected with the WT/NS1 virus. These data agree with cytokine production observed in mouse lungs. Our findings suggest that G45R on NS1 protein contributes to viral virulence by increasing the expression of inflammatory cytokines early in infection. PMID- 27664028 TI - A simple real-time polymerase chain reaction assay using SYBR Green for hepatitis C virus genotyping. AB - Detection of the hepatitis C virus (HCV) genome is crucial for diagnosis of HCV infection and for monitoring the efficacy of HCV treatment. Thus, we aimed to develop a convenient screening test for common HCV genotypes based on melting curve analysis with PCR. Serum samples were drawn from 124 patients with known HCV infection confirmed to be antibody and HCV RNA positive. A characteristic melting curve was obtained by monitoring the fluorescence as the temperature increased through the melting point of the PCR product. Results were compared with those obtained by the restriction fragment length polymorphism (RFLP) genotyping method. The melting curve analysis indicated that the different genotypes had discrete melting points (P < 0.0001): 90.43 +/- 0.065 degrees for genotype 1 (n = 35), 90.21 +/- 0.064 degrees for genotype 2 (n = 18), 90.62 +/- 0.045 degrees for genotype 3 (n = 29) and 90.84 +/- 0.130 degrees for genotype 4 (n = 42). The genotype was determined for all samples using the newly developed method as well as RFLP, and the two systems produced concordant results. The sensitivity of the assay was 91.4 % for genotype 1, 83.3 % for genotype 2, 93.1 % for genotype 3, and 85.7 % for genotype 4. Genotypes detected by melting curve analysis significantly correlated with those detected by RFLP (r = 0.946, P < 0.0001) with a strong linear relationship (r 2 = 0.895). This melting curve analysis is a rapid, convenient and low-cost screening test for differentiation of HCV genotypes 1-4. PMID- 27664029 TI - Recombination between G2 and G6 strains of rabbit hemorrhagic disease virus (RHDV) in China. AB - Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the lagovirus rabbit hemorrhagic disease virus (RHDV), which was first reported in 1984 in China. Genetic characterization of RHDV has demonstrated that two different genogroups (G2 and G6) are present in China. To gain a better understanding of the molecular evolution of RHDV, we searched for recombination events by analyzing all full-length RHDV capsid VP60 sequences of Chinese isolates belonging to the genogroups 2 and 6. Our results revealed a recombinant origin for the NanBu/China/2011 isolate. This recombination event occurred between G2 and G6 strains with two breakpoints located at nucleotide positions 393 and 1079 of the VP60 sequence. Phylogenetically, the NanBu/China/2011 strain clustered with genogroup G6 in the entire capsid gene sequence except in the fragment between nucleotides 394 and 1078, where it clustered with genogroup G2. As the consequences of the presence of a G2/G6 recombinant strain in China are unpredictable, the circulation of RHDV in the populations should be carefully monitored. PMID- 27664030 TI - Glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in Leishmania donovani. AB - Various physiological stimuli trigger the conversion of noninfective Leishmania donovani promastigotes to the infective form. Here, we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. Glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. However, this was reversed by supplementation of gluconeogenic amino acids. Glucose starvation induced metacyclogenesis and enhanced virulence through protein kinase A regulatory subunit (LdPKAR1) mediated autophagy. Glucose starvation driven oxidative stress upregulated the antioxidant machinery, culminating in increased infectivity and greater parasitic load in primary macrophages. Interestingly, phosphoenolpyruvate carboxykinase (LdPEPCK), a gluconeogenic enzyme, exhibited the highest activity under glucose starvation to regulate growth of L. donovani by alternatively utilising amino acids. Deletion of LdPEPCK (Deltapepck) decreased virulent traits and parasitic load in primary macrophages but increased autophagosome formation in the mutant parasites. Furthermore, Deltapepck parasites failed to activate the Pentose Phosphate Pathway shunt, abrogating NADPH/NADP+ homoeostasis, conferring increased susceptibility towards oxidants following glucose starvation. In conclusion, this study showed that L. donovani undertakes metabolic rearrangements via gluconeogenesis under glucose starvation for acquiring virulence and its survival in the hostile environment. PMID- 27664031 TI - C-terminal region of Mad2 plays an important role during mitotic spindle checkpoint in fission yeast Schizosaccharomyces pombe. AB - The mitotic arrest deficiency 2 (Mad2) protein is an essential component of the spindle assembly checkpoint that interacts with Cdc20/Slp1 and inhibit its ability to activate anaphase promoting complex/cyclosome (APC/C). In bladder cancer cell line the C-terminal residue of the mad2 gene has been found to be deleted. In this study we tried to understand the role of the C-terminal region of mad2 on the spindle checkpoint function. To envisage the role of C-terminal region of Mad2, we truncated 25 residues of Mad2 C-terminal region in fission yeast S.pombe and characterized its effect on spindle assembly checkpoint function. The cells containing C-terminal truncation of Mad2 exhibit sensitivity towards microtubule destabilizing agent suggesting perturbation of spindle assembly checkpoint. Further, the C-terminal truncation of Mad2 exhibit reduced viability in the nda3-KM311 mutant background at non-permissive temperature. Truncation in mad2 gene also affects its foci forming ability at unattached kinetochore suggesting that the mad2-?CT mutant is unable to maintain spindle checkpoint activation. However, in response to the defective microtubule, only brief delay of mitotic progression was observed in Mad2 C-terminal truncation mutant. In addition we have shown that the deletion of two beta strands of Mad2 protein abolishes its ability to interact with APC activator protein Slp1/Cdc20. We purpose that the truncation of two beta strands (beta7 and beta8) of Mad2 destabilize the safety belt and affect the Cdc20-Mad2 interaction leading to defects in the spindle checkpoint activation. PMID- 27664032 TI - Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group. AB - In order to investigate whether plasma microRNA-33a (miR-33a) can be a biomarker for the early detection of atherosclerosis and to reexamine the assumption that miR-33a represses the expression of ABCA1, we compared the expression levels of miR-33a and ATP-binding cassette A1 (ABCA1) using human plasma and supernatants of macrophage cultured media. We first separated ample number of plasma samples from left-over whole blood samples based on the criteria for normal or dyslipidemia, and stored them at -20 degrees C until use. Then we selected 18 plasma samples for each normal, athero-risk and treated group using a metabolic disease cohort in which candidate subjects have participated. For classifying into three groups, we primarily relied on the records of physicians' comments, prescriptions, treatment history, lipid profiles and test results from medical equipment aimed at the diagnosis for atherosclerosis or cardiovascular disease. After collecting the final 54 plasma samples, we analyzed and compared the expression levels of miR-33a and ABCA1 at the plasma levels. In the comparison of plasma levels of the three groups, the miR-33a expression level of athero-risk group was 5.01-fold higher than that of normal group. Meanwhile, in the culture of foam cells transfected with anti-miR-33a oligonucleotides, the miR-33a level significantly decreased, while ABCA1 level significantly increased. The results suggest that enhanced expression of miR-33a might induce cholesterol accumulation and aggravate inflammation in vessel walls by suppressing the expression of ABCA1 in macrophages. Thus, plasma miR-33a can be considered as a candidate biomarker of atherosclerosis. PMID- 27664033 TI - Altered Resting-State Signals in Patients with Acute Stroke In or Under the Thalamus. AB - Previous studies have suggested that cortical functional reorganization is associated with motor recovery after stroke and that normal afferent sensory information is very important in that process. In this study, we selected patients who had a stroke in or under the thalamus, with potentially impaired afferent sensory information and analyzed the differences between these patients and healthy controls at three levels: brain regions, the functional connectivity between brain areas, and the whole-brain functional network. Compared with healthy controls, regional homogeneities in the left middle temporal gyrus decreased and functional connectivity between the left middle temporal gyrus and the stroke area increased in the patients. However, there was no significant change in the whole-brain functional network. By focusing on stroke located in or under the thalamus, our study contributes to wider inquiries into understanding and treating stroke. PMID- 27664034 TI - Clinicopathologic features and prognosis of primary gastrointestinal stromal tumor patients under 35 years of age: A 10-year retrospective study. AB - OBJECTIVES: To investigate gastrointestinal stromal tumor (GIST) clinicopathologic characteristics in young adults. METHODS: Clinicopathologic data from GIST patients under 35 years diagnosed at our hospital from January 2005 to December 2014 were retrospectively collected. RESULTS: Thirty-one (5.3%, 31/585) patients were included; 17 (54.8%) were female. The most common presentation and primary tumor site were gastrointestinal bleeding (n = 18, 58.1%) and the small intestine (n = 13, 41.9%), respectively. Fifteen (48.4%) GISTs were classified as having a high relapse risk; two (6.4%), intermediate; nine (29.0%), low; and five (16.1%), very low. All patients underwent tumor resection. With a median follow-up of 51 months for 20 (64.5%) patients, 12 (60%) were given imatinib methylate as adjuvant therapy. One (5%) patient died of peritoneal GIST dissemination, four (20%) developed abdominal recurrences, two (10%) had hepatic metastasis, and thirteen (65%) were disease free. The 5-year disease-free survival rate was 51.2%. CONCLUSIONS: GISTs rarely occur in young adults. The most common location is the small intestine. A slight female predominance was observed in the current study. Adjuvant therapy longer than the recommended duration may be beneficial for GISTs with a high relapse risk. Combined targeted therapy and surgery is appropriate for recurrent and metastatic GISTs in select patients. J. Surg. Oncol. 2016;114:977-981. (c) 2016 Wiley Periodicals, Inc. PMID- 27664036 TI - Facilitators and inhibitors in developing professional values in nursing students. AB - BACKGROUND: Values are the basis of nursing practice, especially in making decisions about complicated ethical issues. Despite their key role in nursing, little information exists on the factors affecting their development and manifestation in nursing students. OBJECTIVE: This study identifies and describes the facilitators and inhibitors of the development and manifestation of professional values based on the experiences of nursing students and instructors and nurses. RESEARCH DESIGN: Data were collected through 29 semi-structured interviews and two focus group interviews in 2013-2015 and were analyzed using the conventional content analysis method of Elo and Kyngas. Participants and research context: In total, 18 nursing undergraduates, five nursing instructors, and five nurses from Shiraz University of Medical Sciences and one of the teaching hospitals in Shiraz were selected through purposive sampling. Ethical considerations: The research was approved by the Ethics Committee of Shiraz University of Medical Sciences and the teaching hospital examined. FINDINGS: The findings consisted of two categories: personal and environmental factors. Personal factors consisted of the two subcategories of personal stimuli (work experience and past relationships, inner beliefs and acting on values, belief in God and a divine worldview) and personal inhibitors (the lack of professional motivation and enthusiasm, negative emotions). Environmental factors consisted of the two subcategories of environmental stimuli (cooperation, order and discipline) and environmental inhibitors (unfavorable work environment, society's negative attitude toward nursing, the violation of rights). DISCUSSION AND CONCLUSION: Given the impact of personal and environmental factors on the development and manifestation of professional values in nursing students, it is upon the education authorities to take account of them in their planning, and nursing managers are also recommended to further address these factors in their development of a proper work environment, provision of standard facilities and removal of barriers. PMID- 27664037 TI - Ethics support in community care makes a difference for practice. AB - BACKGROUND: Through the Norwegian ethics project, ethics activities have been implemented in the health and care sector in more than 200 municipalities. OBJECTIVES: To study outcomes of the ethics activities and examine which factors promote and inhibit significance and sustainability of the activities. RESEARCH DESIGN: Two online questionnaires about the municipal ethics activities. Participants and research context: A total of 137 municipal contact persons for the ethics project answered the first survey (55% response rate), whereas 217 ethics facilitators responded to the second survey (33% response rate). Ethical considerations: Based on informed consent, the study was approved by the Data Protection Official of the Norwegian Social Science Data Services. FINDINGS: Around half of the respondents found the ethics project to have been highly significant for daily professional practice. Outcomes include better handling of ethical challenges, better employee cooperation, better service quality, and better relations to patients and next of kin. Factors associated with sustainability and/or significance of the activities were sufficient support from stakeholders, sufficient available time, and ethics facilitators having sufficient knowledge and skills in ethics and access to supervision. DISCUSSION: This study shows that ethics initiatives can be both sustainable and significant for practice. There is a need to create regional or national structures for follow-up and develop more comprehensive ethics training for ethics facilitators. CONCLUSION: It is both possible and potentially important to implement clinical ethics support activities in community health and care services systematically on a large scale. Future ethics initiatives in the community sector should be designed in light of documented promoting and inhibiting factors. PMID- 27664035 TI - Pioglitazone induces cell growth arrest and activates mitochondrial apoptosis in human uterine leiomyosarcoma cells by a peroxisome proliferator-activated receptor gamma-independent mechanism. AB - The peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, thiazolidinediones, including pioglitazone (PIO) exhibit anti-tumour activities in cancer cells. The present study investigates the effects of PIO on cell proliferation and apoptosis in SK-UT-1 cells, a human uterine leiomyosarcoma cell line, and human uterine smooth muscle cells (HUtSMC). The proliferation and viability of SK-UT-1 cells treated with vehicle or PIO were assessed by cell counting and WST-1 assay. The activity of MEK/ERK and p38 MAPK signalling pathways and the expression of p53, the cyclin-dependent kinase inhibitor, p21, Bax, Bad and Bim proteins and cleaved caspase-3 were analysed by Western blotting. Quiescent SK-UT-1 cells intensively proliferate and display high levels of phosphorylated, activated MEK1/2, ERK1/2 and p38 MAPK. PIO (10 or 25 MUM) induced time- and dose-dependently cell-growth arrest, reduced the cell numbers and effectively suppressed the over-activated MEK/ERK and p38 MAPK signalling pathways as evidenced by the abolished levels of phosphorylated MEK1/2, ERK1/2 and p38 MAPK. PIO activated the intrinsic apoptotic pathway, i.e. up-regulated the p53, p21, Bax and Bad proteins and cleaved caspase-3. PIO also reduced cell numbers of highly proliferative SK-UT-1 cells cultured in growth medium. The anti proliferative and pro-apoptotic actions of PIO were not PPARgamma dependent and exclusive for SK-UT-1 cells as PIO did not interfere with the proliferation of HUtSMC. The pronounced anti-tumorigenic effects of PIO in SK-UT-1 cells address an important issue about the relevance of the PPARgamma agonist in the treatment of the human uterine leiomyosarcoma. PMID- 27664038 TI - Effect of Planned Follow-up on Married Women's Health Beliefs and Behaviors Concerning Breast and Cervical Cancer Screenings. AB - The objective of this study was to identify the effect of planned follow-up visits on married women's health beliefs and behaviors concerning breast and cervical cancer screenings. The study was conducted using the single-group pre test/post-test and quasi-experimental study designs. The sample of the study included 153 women. Data were collected using a Personal Information Form, the Health Belief Model (HBM) Scale for Breast Cancer Screening, the HBM Scale for Cervical Cancer Screening, and a Pap smear test. Data were collected using the aforementioned tools from September 2012 to March 2013. Four follow-up visits were conducted, nurses were educated, and telephone reminders were utilized. Friedman's test, McNemar's test, and descriptive statistics were used for data analyzing. The frequency of performing breast self-examination (BSE) at the last visit increased to 84.3 % compared to the pre-training. A statistically significant difference was observed between the pre- and post-training median values in four subscales except for the subscale of perceived seriousness of cervical cancer under "the Health Belief Model Scale for Cervical Cancer and the Pap Smear Test" (p < 0.001). The rate of performing BSE significantly increased after the training and follow-up visits. Also, the rate of having a Pap smear significantly increased after the follow-up visits. PMID- 27664041 TI - Racial/Ethnic Residential Segregation, Obesity, and Diabetes Mellitus. AB - Persistent racial/ethnic disparities in obesity and type 2 diabetes mellitus seen in the US are likely due to a combination of social, biological, and environmental factors. A growing number of studies have examined the role of racial/ethnic residential segregation with respect to these outcomes because this macro-level process is believed to be a fundamental cause of many of the factors that contribute to these disparities. This review provides an overview of findings from studies of racial/ethnic residential segregation with obesity and diabetes published between 2013 and 2015. Findings for obesity varied by geographic scale of the segregation measure, gender, ethnicity, and racial identity (among Hispanics/Latinos). Recent studies found no association between racial/ethnic residential segregation and diabetes prevalence, but higher segregation of Blacks was related to higher diabetes mortality. Implications of these recent studies are discussed as well as promising areas of future research. PMID- 27664040 TI - Integrated Cardio-Respiratory Control: Insight in Diabetes. AB - Autonomic dysfunction is a frequent and relevant complication of diabetes mellitus, as it is associated with increased morbidity and mortality. In addition, it is today considered as predictive of the most severe diabetic complications, like nephropathy and retinopathy. The classical methods of screening are the cardiovascular reflex tests and were originally interpreted as evidence of nerve damage. A more modern approach, based on the integrated control of cardiovascular and respiratory function, reveals that these abnormalities are to a great extent functional, at least in the early stage of the disease, thus suggesting new potential interventions. Therefore, this review aims to go further investigating how the imbalance of the autonomic nervous system is altered and can be influenced in many chronic pathologies through a global view of cardio respiratory and metabolic interactions and how the same mechanisms are applicable to diabetes. PMID- 27664039 TI - Sleep Duration and Diabetes Risk: Population Trends and Potential Mechanisms. AB - Sleep is important for regulating many physiologic functions that relate to metabolism. Because of this, there is substantial evidence to suggest that sleep habits and sleep disorders are related to diabetes risk. In specific, insufficient sleep duration and/or sleep restriction in the laboratory, poor sleep quality, and sleep disorders such as insomnia and sleep apnea have all been associated with diabetes risk. This research spans epidemiologic and laboratory studies. Both physiologic mechanisms such as insulin resistance, decreased leptin, and increased ghrelin and inflammation and behavioral mechanisms such as increased food intake, impaired decision-making, and increased likelihood of other behavioral risk factors such as smoking, sedentary behavior, and alcohol use predispose to both diabetes and obesity, which itself is an important diabetes risk factor. This review describes the evidence linking sleep and diabetes risk at the population and laboratory levels. PMID- 27664042 TI - The Expanding Role of Natural Killer Cells in Type 1 Diabetes and Immunotherapy. AB - Treatments for autoimmune diseases including type 1 diabetes (T1D) are aimed at resetting the immune system, especially its adaptive arm. The innate immune system is often ignored in the design of novel immune-based therapies. There is increasing evidence for multiple natural killer (NK) subpopulations, but their role is poorly understood in autoimmunity and likely is contributing to the controversial role reported for NKs. In this review, we will summarize NK subsets and their roles in tolerance, autoimmune diabetes, and immunotherapy. PMID- 27664045 TI - Shigellosis murine model established by intraperitoneal and intranasal route of administration: a comparative comprehension overview. AB - Shigellosis, a major cause of mortality and morbidity, requires development of effective intervention strategy for which animal model mimicking human pathology is essential. Among various animal models for shigellosis, mice being more convenient have been used wherein intraperitoneal and intranasal routes are preferred. With the aim to comprehend the comparative pathophysiological indicators, we have examined relatively high and low dose of Shigella flexneri administered through intraperitoneal and intranasal routes in mice. Characterization of these two models along with the resulting pathophysiology of shigellosis adds to our understanding and offers suitable models appropriate to the objectives of the study. PMID- 27664044 TI - Hyponatremia and bone disease. AB - Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1alpha and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients, especially in those receiving medications that can cause hyponatremia. Furthermore, elderly patients with an unsteady gait and/or confusion should be evaluated for the presence of mild hyponatremia, and if present, treatment should be initiated. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and hyponatremia corrected, if present. PMID- 27664046 TI - Hypoxia and inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a general term to describe inflammatory diseases of the gastrointestinal tract such as Crohn's disease and ulcerative colitis. IBD affects approximately 1 in 200 individuals and exerts a significant health and quality of life burden on patients. Surgical intervention can be curative in ulcerative colitis but there is currently no cure for Crohn's disease. Since this is the case, and the fact that patients are often diagnosed at a young age, IBD exerts a significant financial burden on the health care system, and society as a whole. The underlying pathology of IBD is complex and involves a combination of genetic, environmental and microbial factors. Regardless of the underlying causes of the condition, this disease is universally characterized by disruption to the protective epithelial barrier separating the intestinal lumen above from the mucosal immune system below. Once this barrier becomes compromised a sequence of events ensues, that can occur in repetitive cycles to ensure long-term and serious damage to the gut. The role of hypoxia and hypoxia-dependent signalling pathways are increasingly appreciated to play a role in the physiology and pathophysiology of the intestine. The intestinal epithelium normally exists in a state of physiological hypoxia, with additional tissue hypoxia a feature of active inflammatory disease. Furthermore, recent pre clinical animal studies have clearly supported the rationale for pharmacologically manipulating the oxygen-sensitive hypoxia-inducible factor (HIF) pathway in models of IBD. Thus, this review will discuss the contribution of hypoxia sensitive pathways in the pathology of IBD. Finally we will discuss the emerging evidence for manipulation of hypoxia-sensitive pathways in the treatment of IBD. PMID- 27664043 TI - Restoring Regulatory T Cells in Type 1 Diabetes. AB - Genetic and cellular studies of type 1 diabetes in patients and in the nonobese diabetic mouse model of type 1 diabetes point to an imbalance between effector T cells and regulatory T cells (Tregs) as a driver of the disease. The imbalance may arise as a consequence of genetically encoded defects in thymic deletion of islet antigen-specific T cells, induction of islet antigen-specific thymic Tregs, unfavorable tissue environment for peripheral Treg induction, and failure of islet antigen-specific Tregs to survive in the inflamed islets secondary to insufficient IL-2 signals. These understandings are the foundation for rationalized design of new therapeutic interventions to restore the balance by selectively targeting effector T cells and boosting Tregs. PMID- 27664048 TI - Celebration of the 50th anniversary of IgE discovery. PMID- 27664047 TI - Three-base periodicity of sites of sequence variation in Pseudomonas aeruginosa and Staphylococcus aureus core genomes. AB - The three-base periodicity property is characteristic of protein-coding sequences. Here, we report on three-base periodicity of sequence variation in the core genome of bacteria. Single nucleotide polymorphism (SNP) syntenies were extracted from pairwise genome alignments of 41 Staphylococcus aureus or 20 Pseudomonas aeruginosa strains. The length of fragment pairs with identical nucleotides at all SNP positions showed a length-dependent overrepresentation of multiples of three nucleotides at corresponding codon positions of the AT-rich S. aureus and the GC-rich P. aeruginosa. Three-base SNP periodicity seems to be a characteristic feature of the tightly arranged bacterial core genome. PMID- 27664049 TI - The Relative Abundance and Transcriptional Activity of Marine Sponge-Associated Microorganisms Emphasizing Groups Involved in Sulfur Cycle. AB - During the last decades, our knowledge about the activity of sponge-associated microorganisms and their contribution to biogeochemical cycling has gradually increased. Functional groups involved in carbon and nitrogen metabolism are well documented, whereas knowledge about microorganisms involved in the sulfur cycle is still limited. Both sulfate reduction and sulfide oxidation has been detected in the cold water sponge Geodia barretti from Korsfjord in Norway, and with specimens from this site, the present study aims to identify extant versus active sponge-associated microbiota with focus on sulfur metabolism. Comparative analysis of small subunit ribosomal RNA (16S rRNA) gene (DNA) and transcript (complementary DNA (cDNA)) libraries revealed profound differences. The transcript library was predominated by Chloroflexi despite their low abundance in the gene library. An opposite result was found for Acidobacteria. Proteobacteria were detected in both libraries with representatives of the Alpha- and Gammaproteobacteria related to clades with presumably thiotrophic bacteria from sponges and other marine invertebrates. Sequences that clustered with sponge associated Deltaproteobacteria were remotely related to cultivated sulfate reducing bacteria. The microbes involved in sulfur cycling were identified by the functional gene aprA (adenosine-5'-phosphosulfate reductase) and its transcript. Of the aprA sequences (DNA and cDNA), 87 % affiliated with sulfur-oxidizing bacteria. They clustered with Alphaproteobacteria and with clades of deep branching Gammaproteobacteria. The remaining sequences clustered with sulfate reducing Archaea of the phylum Euryarchaeota. These results indicate an active role of yet uncharacterized Bacteria and Archaea in the sponge's sulfur cycle. PMID- 27664053 TI - D-Phenylalanine inhibits biofilm development of a marine microbe, Pseudoalteromonas sp. SC2014. AB - D-Amino acids have been reported to be able to inhibit biofilm formation or disperse existing biofilms of many microbes; in some cases this is due to growth inhibition as an unspecific effect. In this work, six different D-amino acids were tested for their inhibitory effects on biofilm development and bacterial growth of Pseudoalteromonas sp. SC2014, a marine microbe involved in microbiologically influenced corrosion (MIC). Experimental results indicated that D-phenylalanine (D-Phe) inhibited biofilm formation effectively at concentrations that did not affect cell growth, whereas the other D-amino acids either showed little effect or inhibited biofilm formation while inhibiting bacterial growth. Further studies found that D-Phe could inhibit bacterial accumulation on the surface of 316L stainless steel, and prevent bacteria from forming a multilayer biofilm. It was also suggested that D-Phe could promote the disassembly of an established multilayer biofilm but have little effect on the remaining monolayer adherent cells. For the first time, it was found that a D-amino acid could effectively inhibit biofilm formation of an MIC-involved microbe. This might supply a new insight into how MIC could be mitigated. PMID- 27664051 TI - An Okinawan-based Nordic diet improves anthropometry, metabolic control, and health-related quality of life in Scandinavian patients with type 2 diabetes: a pilot trial. AB - BACKGROUND: Our hypothesis was that a modified diet would improve blood glucose control with beneficial impact on weight management and overall health in established diabetes. OBJECTIVE: This prospective interventional study investigated the clinical effect of an Okinawan-based Nordic diet on anthropometry, metabolic control, and health-related quality of life (HRQoL) in Scandinavian type 2 diabetes patients. DESIGN: Food was prepared and delivered to 30 type 2 diabetes patients. Clinical information along with data on HRQoL, blood samples, and urine samples were collected during 12 weeks of diet interventions, with follow-up 16 weeks after diet completion. RESULTS: After 12 weeks of dietary intervention, a reduction in body weight (7%) (p<0.001), body mass index (p<0.001), and waist circumference (7.0 cm) (p<0.001) was seen. Improved levels of proinsulin (p=0.005), insulin (p=0.011), and fasting plasma glucose (p<0.001) were found already after 2 weeks; these improved levels remained after 12 weeks when lowered levels of C-peptide (p=0.015), triglycerides (p=0.009), total cholesterol (p=0.001), and low-density lipoprotein-cholesterol (p=0.041) were also observed. Insulin resistance homeostasis model assessment for insulin resistance was lowered throughout the study, with a 20% reduction in hemoglobin A1c levels (p<0.001) at week 12, despite reduced anti-diabetes treatment. Lowered systolic blood pressure (9.6 mmHg) (p<0.001), diastolic blood pressure (2.7 mmHg) (p<0.001), and heart and respiratory rates (p<0.001) were accompanied by decreased cortisol levels (p=0.015) and improvement in HRQoL. At follow-up, increased levels of high-density lipoprotein-cholesterol were found (p=0.003). CONCLUSION: This interventional study demonstrates a considerable improvement of anthropometric and metabolic parameters and HRQoL in Scandinavian type 2 diabetes patients when introducing a modified Okinawan-based Nordic diet, independently of exercise or other interventions. Through these dietary changes, anti-diabetes treatment could be decreased or cancelled. PMID- 27664050 TI - Co-expression of p16 and p53 characterizes aggressive subtypes of ductal intraepithelial neoplasia. AB - In the USA alone, approximately 61,000 new diagnoses of ductal intraepithelial neoplasia 1c-3 (DIN) are made each year. Around 10-20 % of the patients develop a recurrence, about 50 % of which are invasive. Prior studies have shown that invasive breast carcinomas positive for p16 or p53 have a higher frequency of recurrence and a more aggressive course; however, the co-expression of these markers across the entire spectrum of DIN and its potential correlation with grade of the lesions has not been studied previously. Immunohistochemical staining for p16 and p53 was evaluated on 262 DIN lesions from 211 cases diagnosed between 1991 and 2008. The lesions ranged from DIN1b (atypical intraductal hyperplasia) to DIN3 (DCIS, grade 3) and included 45 cases with associated invasive carcinoma. Frequency of staining for both p16 and p53 increased with increasing grade of DIN. Strong co-expression was found exclusively in higher grade DIN lesions (DIN2 and DIN3) particularly those associated with periductal stromal fibrosis and lymphocytic infiltrate. Strong co expression was seen in 8 of 12 DIN3 lesions (67 %) associated with invasive carcinoma. In conclusion, co-expression of p16 and p53 increases with advancing grade of DIN and is maximal in high grade DIN lesions associated with invasive carcinoma, indicating a more aggressive phenotype. A distinctive variant of DIN with periductal fibrosis and lymphocytic infiltrate invariably falls into the high-grade category, based on either morphology or marker expression. Co expression of p16/p53 may be of help in distinguishing between high-grade and low grade DIN lesions. PMID- 27664052 TI - Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia. AB - Ataxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in the ATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers. We found 28 ATM gene mutations, of which 10 have not been reported. A total of 171 gene variants not affecting function were also found, of which 22 are reported to predispose to disease. Interestingly, all Roma (Spanish Gypsies) patients are homozygous for the same mutation and share the H3 ATM haplotype, which is strong evidence of a founder effect in this population. In addition, we generated a panel of 27 primary T cell lines from A-T patients, which revealed significant expression of ATM in two patients and traces of the protein in nine more. None of them retained residual ATM activity, and almost all T cell lines show increased or intermediate radiosensitivity. PMID- 27664054 TI - Preparation and evaluation of MS2 bacteriophage-like particles packaging hepatitis E virus RNA. AB - Hepatitis E virus (HEV) is the pathogen causing hepatitis E (HE). It arouses global public health concern since it is a zoonotic disease. The objective of this letter is to report a cost-effective internal control prepared for monitoring procedures of HEV reverse transcriptase (RT)-PCR detection. A selected conserved HEV RNA fragment was integrated into the downstream of the truncated MS2 bacteriophage genome based on Armored RNA technology. The resulting MS2-HEV gene harbored by the pET-28b-MS2-HEV plasmid was transformed into E. coli BL21(DE3) for expression analysis by SDS-PAGE. The expression products were purified and concentrated by ultrasonication and ultrafiltration separation. The morphology and stability properties of the virus-like particles (VLPs) were evaluated by electron microscopy scanning and nuclease challenges, respectively. SDS-PAGE results showed that the constructed MS2-HEV gene expressed efficiently and the purity of the VLPs was highly consistent with the result in electron microscopy. Stability evaluation results demonstrated that the prepared VLPs exhibited strong resistance to DNase I and RNase A attacks and also performed long-lasting protection of coated HEV RNA for at least 4 months at -20 degrees C. These data revealed that the prepared VLPs meet the basic requirements of use as internal control material in the HEV RNA amplification assay. PMID- 27664056 TI - The transcriptional factor TtsI is involved in a negative regulation of swimming motility in Mesorhizobium loti MAFF303099. AB - Mesorhizobium loti MAFF303099 has a functional Type III secretion system (T3SS) that is involved in the determination of competitiveness for legume nodulation. Here we demonstrate that the transcriptional factor TtsI, which positively regulates T3SS genes expression, is involved in a negative regulation of M. loti swimming motility in soft-agar. Conditions that induce T3SS expression affect flagella production. The same conditions also affect promoter activity of M. loti visN gene, a homolog to the positive regulator of flagellar genes that has been described in other rhizobia. Defects in T3SS complex assembly at membranes limited the negative regulation of motility by the expression of TtsI. PMID- 27664057 TI - The emerging problems of Klebsiella pneumoniae infections: carbapenem resistance and biofilm formation. AB - Klebsiella pneumoniae is an opportunistic pathogen that commonly causes nosocomial infections in the urinary tract, respiratory tract, lung, wound sites and blood in individuals with debilitating diseases. Klebsiella pneumoniae is still a cause of severe pneumonia in alcoholics in Africa and Asia, and the predominant primary pathogen of primary liver abscess in Taiwan and Southeast Asia, particularly in Asian and Hispanic patients, and individuals with diabetes mellitus. In the United States and Europe, K. pneumoniae infections are most frequently associated with nosocomial infections. The emergence of antibiotic resistant strains of K. pneumoniae worldwide has become a cause of concern where extended-spectrum beta-lactamases (ESBLs) and carbapenemase-producing strains have been isolated with increasing frequency. The pathogen's ability to form biofilms on inserted devices such as urinary catheter has been proposed as one of the important mechanisms in nosocomially acquired and persistent infections, adding to the increased resistance to currently used antibiotics. In this review, infections caused by K. pneumoniae, antibiotic resistance and formation of biofilm will be discussed. PMID- 27664058 TI - Incidence of diverse dsRNA mycoviruses in Trichoderma spp. causing green mold disease of shiitake Lentinula edodes. AB - A total of 315 fungal isolates causing green mold disease were collected from contaminated artificial logs and sawdust bags used for cultivating shiitake Lentinula edodes in Korea and were analyzed for the presence of double-stranded RNA (dsRNA). dsRNA, which was purified using dsRNA-specific chromatography and verified by dsRNA-specific RNaseIII digestion, was detected in 32 isolates. The molecular taxonomy of dsRNA-infected isolates indicated that all isolates belonged to the Trichoderma spp.. The number and size of dsRNAs varied among isolates and the band patterns could be categorized into 15 groups. Although there were seven dsRNA groups observed in multiple isolates, eight groups were found to occur in single isolates. The most common dsRNA group, group VI, which contained a band of 10 kb, occurred in 10 isolates encompassing three species of Trichoderma Partial sequence analysis of two selected dsRNA groups revealed a high degree of similarity to sequences of a RNA-dependent RNA polymerase, hypothetical protein, and polyprotein genes of other hypoviruses such as Macrophomina phaseolina hypovirus 1, Trichoderma hypovirus, and Fusarium graminearum hypovirus 2, respectively, indicating the occurrence of mycoviruses in Trichoderma spp.. Northern blot analysis suggested that many different mycoviruses, which have not been identified yet, exist in Trichoderma. PMID- 27664055 TI - Transcriptomic analysis of the highly efficient oil-degrading bacterium Acinetobacter venetianus RAG-1 reveals genes important in dodecane uptake and utilization. AB - The hydrocarbonoclastic bacterium Acinetobacter venetianus RAG-1 has attracted substantial attention due to its powerful oil-degrading capabilities and its potential to play an important ecological role in the cleanup of alkanes. In this study, we compare the transcriptome of the strain RAG-1 grown in dodecane, the corresponding alkanol (dodecanol), and sodium acetate for the characterization of genes involved in dodecane uptake and utilization. Comparison of the transcriptional responses of RAG-1 grown on dodecane led to the identification of 1074 genes that were differentially expressed relative to sodium acetate. Of these, 622 genes were upregulated when grown in dodecane. The highly upregulated genes were involved in alkane catabolism, along with stress response. Our data suggest AlkMb to be primarily involved in dodecane oxidation. Transcriptional response of RAG-1 grown on dodecane relative to dodecanol also led to the identification of permease, outer membrane protein and thin fimbriae coding genes potentially involved in dodecane uptake. This study provides the first model for key genes involved in alkane uptake and metabolism in A. venetianus RAG-1. PMID- 27664059 TI - Pharmacy use by dual-eligible non-elderly veterans with private healthcare insurance. AB - BACKGROUND: Utilization of private sector healthcare services among dual enrolled veterans with private healthcare insurance plans (PHIP) has not been well characterized. Concurrent use of Veterans Health Administration (VHA) and non-VHA pharmacies may increase risk for adverse outcomes. Thus, the objectives of this study were to determine the extent to which dual VHA-PHIP enrollees obtain medications through VHA and non-VHA pharmacies and to characterize medications obtained through non-VHA pharmacies. METHODS: This observational study used merged administrative data from VHA and a predominant regional PHIP to select veterans < 65 years of age, residing in two Midwestern US states, and simultaneously enrolled in both VHA and the PHIP during fiscal years (FY) 2001 2010. Primary outcome measures included counts of prescriptions dispensed from VHA and non-VHA pharmacies, and frequencies of medications dispensed by non-VHA pharmacies based on PHIP claims. RESULTS: Of 5783 veterans who filled >= 1 prescription in FY10, 2935 (50.8 %) used non-VHA pharmacies exclusively, 1165 (20.2 %) used VHA pharmacies exclusively and 1683 (29.1 %) were dual users. Health services utilization was higher for dual users compared to exclusive users of either VHA or non-VHA pharmacies across multiple measures, including total prescriptions, outpatient encounters, and inpatient admissions. The most common medications dispensed by non-VHA pharmacies, by proportion of veterans treated, were hydrocodone (20.9 %), amoxicillin (18.5 %), simvastatin (17.5 %), azithromycin (17.4 %), and lisinopril (15.1 %). Antidepressants comprised 3 of 10 most common medications dispensed by VHA, but none of the most common medications dispensed to exclusive non-VHA pharmacy users. CONCLUSIONS: Our findings align with VHA-Medicare dual enrolled veterans where only a minority of veterans used VHA services exclusively. Younger veterans relied disproportionately on VHA for mental health medications. PMID- 27664063 TI - GRK2 targeted knock-down results in spontaneous hypertension, and altered vascular GPCR signaling. PMID- 27664062 TI - Ease of Use of the Insulin Glargine 300 U/mL Pen Injector in Insulin-Naive People With Type 2 Diabetes. AB - BACKGROUND: Insulin glargine 300 U/mL (Gla-300) contains the same active ingredient as glargine 100 U/mL (Gla-100), and provides the same number of units in one-third of the volume. The SoloSTAR(r) injector pen has been modified to ensure accurate administration of this reduced volume and to improve user experience. METHODS: Insulin- and pen-naive adults with type 2 diabetes (T2DM) inadequately controlled with oral antihyperglycemic drugs, who had glycated hemoglobin (HbA1c) levels of 7.0-11.0 % (53-97 mmol/mol) were studied. They received once-daily Gla-300 in this 4-week, multicenter, open-label, single-arm study (NCT02227212). Ease of use/ease of learning (the primary endpoint), glycemic control, safety, and reliability of the disposable (prefilled) Gla-300 injector pen (secondary endpoints) were evaluated. RESULTS: At week 4, 95.0% of 40 participating subjects assessed the pen as excellent/good and none as poor/very poor; 97.5% would recommend it to others. Total Diabetes Treatment Satisfaction Questionnaire scores were stable throughout the study. Mean (SD) fasting plasma glucose levels decreased from 166.1 (35.0) mg/dL at baseline to 124.2 (41.1) mg/dL at week 4. No product technical complaints (PTCs) or adverse events (AEs) related to PTCs were reported. The number of subjects experiencing hypoglycemic events of any kind and the incidence of AEs were low. No serious AEs were reported. CONCLUSIONS: The Gla-300 injector pen is easy to use and easy to learn to use, with demonstrable reliability and high degrees of acceptance and treatment satisfaction. Once-daily Gla-300 basal insulin treatment was well tolerated and effective in pen- and insulin-naive adult T2DM subjects. PMID- 27664064 TI - Multiple cyclin kinase inhibitors promote bile acid-induced apoptosis and autophagy in primary hepatocytes via p53-CD95-dependent signaling. PMID- 27664066 TI - Distinct requirements for 5'-monophosphate-assisted RNA cleavage by Escherichia coli RNase E and RNase G. PMID- 27664065 TI - Role of the JP45-calsequestrin complex on calcium entry in slow twitch skeletal muscles. PMID- 27664067 TI - The transcription factor SPDEF suppresses prostate tumor metastasis. PMID- 27664068 TI - CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca2+ channels upstream of p38 MAPK. AB - BACKGROUND: The chemokine receptor CXCR4 (CD184) and its natural ligand CXCL12 contribute to many physiological processes, including decisions about cell death and survival in the central nervous system. In addition, CXCR4 is a co-receptor for human immunodeficiency virus (HIV)-1 and mediates the neurotoxicity of the viral envelope protein gp120. However, we previously observed that CXCL12 also causes toxicity in cerebrocortical neurons but the cellular mechanism remained incompletely defined. METHODS: Primary neuronal-glial cerebrocortical cell cultures from rat were exposed to a neurotoxicity-inducing CXCL12 concentration for different times and the activity of the stress-associated mitogen-activated protein kinase p38 (p38 MAPK) was assessed using an in vitro kinase assay. Neurotoxicity of CXCL12 and cellular localization of p38 MAPK was analyzed by immunofluorescence microscopy. Pharmacological inhibition of NMDA-type glutamate receptor-gated ion channels (NMDAR) of L-type Ca2+ channels was employed during 12- and 24-h exposure to neurotoxic amounts of CXCL12 to study the effects on active p38 MAPK and neuronal survival by Western blotting and microscopy, respectively. Neurotoxicity of CXCL12 was also assessed during pharmacological inhibition of p38 MAPK. RESULTS: Here, we show that a neurotoxic amount of CXCL12 triggers a significant increase of endogenous p38 MAPK activity in cerebrocortical cells. Immunofluorescence and Western blotting experiments with mixed neuronal-glial and neuron-depleted glial cerebrocortical cells revealed that the majority of active/phosphorylated p38 MAPK was located in neurons. Blockade of NMDAR-gated ion channels or L-type Ca2+ channels both abrogated an increase of active p38 MAPK and toxicity of CXCL12 in cerebrocortical neurons. Inhibition of L-type Ca2+ channels with nimodipine kept the active kinase at levels not significantly different from baseline while blocking NMDAR with MK-801 strongly reduced phosphorylated p38 MAPK below baseline. Finally, we confirmed that directly blocking p38 MAPK also abrogated neurotoxicity of CXCL12. CONCLUSIONS: Our findings link CXCL12-induced neuronal death to the regulation of NMDAR-gated ion channels and L-type Ca2+ channels upstream of p38 MAPK activation. PMID- 27664070 TI - The use of relative incidence ratios in self-controlled case series studies: an overview. AB - BACKGROUND: The self-controlled case series (SCCS) is a useful design for investigating associations between outcomes and transient exposures. The SCCS design controls for all fixed covariates, but effect modification can still occur. This can be evaluated by including interaction terms in the model which, when exponentiated, can be interpreted as a relative incidence ratio (RIR): the change in relative incidence (RI) for a unit change in an effect modifier. METHODS: We conducted a scoping review to investigate the use of RIRs in published primary SCCS studies, and conducted a case-study in one of our own primary SCCS studies to illustrate the use of RIRs within an SCCS analysis to investigate subgroup effects in the context of comparing whole cell (wcp) and acellular (acp) pertussis vaccines. Using this case study, we also illustrated the potential utility of RIRs in addressing the healthy vaccinee effect (HVE) in vaccine safety surveillance studies. RESULTS: Our scoping review identified 122 primary studies reporting an SCCS analysis. Of these, 24 described the use of interaction terms to test for effect modification. 21 of 24 studies reported stratum specific RIs, 22 of 24 reported the p-value for interaction, and less than half (10 of 24) reported the estimate of the interaction term/RIR, the stratum specific RIs and interaction p-values. Our case-study demonstrated that there was a nearly two-fold greater RI of ER visits and admissions following wcp vaccination relative to acp vaccination (RIR = 1.82, 95 % CI 1.64-2.01), where RI estimates in each subgroup were clearly impacted by a strong healthy vaccinee effect. CONCLUSIONS: We demonstrated in our scoping review that calculating RIRs is not a widely utilized strategy. We showed that calculating RIRs across time periods is useful for the detection of relative changes in adverse event rates that might otherwise be missed due to the HVE. Many published studies of vaccine associated adverse events could have missed/underestimated important safety signals masked by the HVE. With further development, our application of RIRs could be an important tool to address the HVE, particularly in the context of self-controlled study designs. PMID- 27664071 TI - Compassion interventions: The programmes, the evidence, and implications for research and practice. AB - PURPOSE: Over the last 10-15 years, there has been a substantive increase in compassion-based interventions aiming to improve psychological functioning and well-being. METHODS: This study provides an overview and synthesis of the currently available compassion-based interventions. What do these programmes looks like, what are their aims, and what is the state of evidence underpinning each of them? RESULTS: This overview has found at least eight different compassion-based interventions (e.g., Compassion-Focused Therapy, Mindful Self Compassion, Cultivating Compassion Training, Cognitively Based Compassion Training), with six having been evaluated in randomized controlled trials, and with a recent meta-analysis finding that compassion-based interventions produce moderate effect sizes for suffering and improved life satisfaction. CONCLUSIONS: Although further research is warranted, the current state of evidence highlights the potential benefits of compassion-based interventions on a range of outcomes that clinicians can use in clinical practice with clients. PRACTITIONER POINTS: There are eight established compassion intervention programmes with six having RCT evidence. The most evaluated intervention to date is compassion-focused therapy. Further RCTs are needed in clinical populations for all compassion interventions. Ten recommendations are provided to improve the evidence-base of compassion interventions. PMID- 27664069 TI - Relationship between bone mineral density and dietary intake of beta-carotene, vitamin C, zinc and vegetables in postmenopausal Korean women: a cross-sectional study. AB - Objective To examine the relationship between nutritional intake and bone mineral density (BMD) in postmenopausal Korean women. Methods Dietary intake was recorded in postmenopausal Korean women using a semiquantitative questionnaire. The frequency of consumption of various food groups and nutrient intake were calculated. BMD T-scores were measured at the lumbar spine, femoral neck and total hip using dual-energy X-ray absorptiometry. Associations between T-scores and dietary intake were analysed using partial correlation coefficients and multiple linear regression analysis. Results A total of 189 postmenopausal women were included in the study. beta-Carotene intake was positively correlated with the lumbar spine T-score. Sodium and vitamin C intake were positively associated and folate intake negatively associated with the femoral neck T-score. Sodium, zinc and vitamin C intake were positively correlated and potassium intake was negatively correlated with the total hip T-score. Vegetable intake showed a positive association with the femoral neck and total hip T-scores. Conclusion In postmenopausal Korean women, beta-carotene, vitamin C, zinc and sodium intakes were positively associated with bone mass. Furthermore, frequency of vegetable consumption was positively associated with femoral neck and total hip T-scores. PMID- 27664072 TI - Exploring methods the for selection and integration of stakeholder views in the development of core outcome sets: a case study in reconstructive breast surgery. AB - BACKGROUND: The development and use of core outcome sets (COSs) in trials may improve data synthesis and reduce outcome reporting bias. The selection of outcomes in COSs is informed by views of key stakeholders, yet little is known about the role and influence of different stakeholders' views during COS development. We report an exploratory case study examining how stakeholder selection and incorporation of stakeholders' views may influence the selection of outcomes for a COS in reconstructive breast surgery (RBS). We also make recommendations for future considerations. METHODS: Key stakeholder groups and subgroups were identified from the literature and expert opinion by the COS management group. They included health care professionals, subdivided by profession (breast and plastic surgeons, specialist nurses and psychologists) and patients, subdivided according to type of surgery received, timing of reconstruction, time since surgery and patient age. All participated in a survey in which they were asked to prioritise outcomes. Outcomes were prioritised using a 9-point scale from 1 (not important) to 9 (extremely important). The proportion of (1) all participants, ignoring stakeholder group (single heterogeneous panel analysis), (2) 'professional' and 'patient' groups separately (two heterogeneous panels), ignoring prespecified subgroups and (3) each participant subgroup separately (multiple homogeneous panel analysis) rating each item 'extremely important' was summarised and compared to explore how selection and integration of stakeholder views may influence outcome prioritisation. RESULTS: There were many overlaps between items rated as most important by all groups. Specific stakeholders, however, prioritised specific concerns and a broader range of outcomes were prioritised when the subgroups were considered separately. For example, two additional outcomes were prioritised when patient and professional groups were considered separately and eight additional outcomes were identified when the views of the individual subgroups were explored. In general, patient subgroups preferentially valued additional clinical outcomes, including unplanned surgery, whereas professional subgroups prioritised additional psychosocial issues including body image. CONCLUSION: Stakeholder groups value different outcomes. Selection of groups, therefore, is important. Our recommendations for robust and transparent stakeholder selection and integration of stakeholder views may aid future COS developers in the design and conduct of their studies and improve the validity and value of future COS. PMID- 27664073 TI - Midbrain hemiatrophy and nigral rarefaction in a patient with hemiparkinsonism hemiatrophy syndrome. PMID- 27664074 TI - An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial. AB - BACKGROUND: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin +/- aspirin) for prescription when appropriate; and access to a pharmacy based program to support long-term medication adherence and lifestyle modification. METHODS: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. DISCUSSION: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000233426. PMID- 27664075 TI - Coagulation at the crossroads of the communicable/non-communicable disease dyad: The case of pneumonia. PMID- 27664076 TI - Thermocline deepening boosts ecosystem metabolism: evidence from a large-scale lake enclosure experiment simulating a summer storm. AB - Extreme weather events can pervasively influence ecosystems. Observations in lakes indicate that severe storms in particular can have pronounced ecosystem scale consequences, but the underlying mechanisms have not been rigorously assessed in experiments. One major effect of storms on lakes is the redistribution of mineral resources and plankton communities as a result of abrupt thermocline deepening. We aimed at elucidating the importance of this effect by mimicking in replicated large enclosures (each 9 m in diameter, ca. 20 m deep, ca. 1300 m3 in volume) a mixing event caused by a severe natural storm that was previously observed in a deep clear-water lake. Metabolic rates were derived from diel changes in vertical profiles of dissolved oxygen concentrations using a Bayesian modelling approach, based on high-frequency measurements. Experimental thermocline deepening stimulated daily gross primary production (GPP) in surface waters by an average of 63% for >4 weeks even though thermal stratification re-established within 5 days. Ecosystem respiration (ER) was tightly coupled to GPP, exceeding that in control enclosures by 53% over the same period. As GPP responded more strongly than ER, net ecosystem productivity (NEP) of the entire water column was also increased. These protracted increases in ecosystem metabolism and autotrophy were driven by a proliferation of inedible filamentous cyanobacteria released from light and nutrient limitation after they were entrained from below the thermocline into the surface water. Thus, thermocline deepening by a single severe storm can induce prolonged responses of lake ecosystem metabolism independent of other storm-induced effects, such as inputs of terrestrial materials by increased catchment run-off. This highlights that future shifts in frequency, severity or timing of storms are an important component of climate change, whose impacts on lake thermal structure will superimpose upon climate trends to influence algal dynamics and organic matter cycling in clear-water lakes. PMID- 27664077 TI - Exercise-Enhanced, Ultrasound-Guided Anterior Scalene Muscle/Pectoralis Minor Muscle Blocks Can Facilitate the Diagnosis of Neurogenic Thoracic Outlet Syndrome in the High-Performance Overhead Athlete. PMID- 27664078 TI - A Framework for Assessing Uncertainty Associated with Human Health Risks from MSW Landfill Leachate Contamination. AB - Landfilling is a cost-effective method, which makes it a widely used practice around the world, especially in developing countries. However, because of the improper management of landfills, high leachate leakage can have adverse impacts on soils, plants, groundwater, aquatic organisms, and, subsequently, human health. A comprehensive survey of the literature finds that the probabilistic quantification of uncertainty based on estimations of the human health risks due to landfill leachate contamination has rarely been reported. Hence, in the present study, the uncertainty about the human health risks from municipal solid waste landfill leachate contamination to children and adults was quantified to investigate its long-term risks by using a Monte Carlo simulation framework for selected heavy metals. The Turbhe sanitary landfill of Navi Mumbai, India, which was commissioned in the recent past, was selected to understand the fate and transport of heavy metals in leachate. A large residential area is located near the site, which makes the risk assessment problem both crucial and challenging. In this article, an integral approach in the form of a framework has been proposed to quantify the uncertainty that is intrinsic to human health risk estimation. A set of nonparametric cubic splines was fitted to identify the nonlinear seasonal trend in leachate quality parameters. LandSim 2.5, a landfill simulator, was used to simulate the landfill activities for various time slices, and further uncertainty in noncarcinogenic human health risk was estimated using a Monte Carlo simulation followed by univariate and multivariate sensitivity analyses. PMID- 27664079 TI - Systematic review and meta-analysis of randomised trials of perioperative outcomes comparing robot-assisted versus open radical cystectomy. AB - BACKGROUND: With the introduction of robotic surgery, whether the robot-assisted radical cystectomy (RARC) could reduce the perioperative morbidity compared with Open radical cystectomy (ORC) was unknown. METHODS: Studies reported RARC were reviewed based on all randomized controlled trials (RCTs), which focused on the efficacy of RARC versus ORC. RESULTS: Of the 201 studies from preliminary screening, four RCTs were included. By pooling these studies, there were significant differences in comparison of operative time (p = 0.007), estimated blood loss (EBL) (p < 0.001) and time to diet (p < 0.001) between the RARC group and ORC groups. There was no significant difference regarding perioperative complications (Clavien 2-5, Clavien 3-5), length of stay (LOS), positive surgical margins (PSM) and lymph node positive. CONCLUSION: This meta-analysis presented evidence for a benefit of EBL, time to diet, similar perioperative complications and oncological outcomes, but a longer operative time in RARC. It is noted that RARC was considered as a comparable surgical procedure to ORC. PMID- 27664080 TI - Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis. AB - Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a leading cause of autism. FXS is due to the silencing of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein mainly involved in translational control, dendritic spine morphology and synaptic plasticity. Despite extensive studies, there is currently no cure for FXS. With the purpose to decipher the initial molecular events leading to this pathology, we developed a stem-cell-based disease model by knocking-down the expression of Fmr1 in mouse embryonic stem cells (ESCs). Repressing FMRP in ESCs increased the expression of amyloid precursor protein (APP) and Ascl1. When inducing neuronal differentiation, betaIII-tubulin, p27kip1 , NeuN, and NeuroD1 were upregulated, leading to an accelerated neuronal differentiation that was partially compensated at later stages. Interestingly, we observed that neurogenesis is also accelerated in the embryonic brain of Fmr1-knockout mice, indicating that our cellular model recapitulates the molecular alterations present in vivo. Importantly, we rescued the main phenotype of the Fmr1 knockdown cell line, not only by reintroducing FMRP but also by pharmacologically targeting APP processing, showing the role of this protein in the pathophysiology of FXS during the earliest steps of neurogenesis. Our work allows to define an early therapeutic window but also to identify more effective molecules for treating this disorder. Stem Cells 2017;35:374-385. PMID- 27664081 TI - Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration. AB - Terminal liver disease is a major cause of death globally. The only ultimate therapeutic approach is orthotopic liver transplant. Because of the innate defects of organ transplantation, stem cell-based therapy has emerged as an effective alternative, based on the capacity of stem cells for multilineage differentiation and their homing to injured sites. However, the disease etiology, cell type, timing of cellular graft, therapeutic dose, delivery route, and choice of endpoints have varied between studies, leading to different, even divergent, results. In-vivo cell imaging could therefore help us better understand the fate and behaviors of stem cells to optimize cell-based therapy for liver regeneration. The primary imaging techniques in preclinical or clinical studies have consisted of optical imaging, magnetic resonance imaging, radionuclide imaging, reporter gene imaging, and Y chromosome-based fluorescence in-situ hybridization imaging. More attention has been focused on developing new or modified imaging methods for longitudinal and high-efficiency tracing. Herein, we provide a descriptive overview of imaging modalities and discuss recent advances in the field of molecular imaging of intrahepatic stem cell grafts. PMID- 27664082 TI - Association of metabolic syndrome with various anthropometric and atherogenic parameters in the Kazakh population in China. AB - BACKGROUND: This study aimed to evaluate the association of the metabolic syndrome (MetS) with various anthropometric and atherogenic parameters in adult Kazakh population in China. METHODS: Four thousand ninety-four Kazakhs were recruited since 2007 to 2010. MetS and its components were confirmed according to IDF criteria. Area under the curve (AUC) of each variable was compared. Sensitivity (Sen), specificity (Spe), shortest distance in receiver's operating characteristic curve (ROC) and cutoff of each variable to diagnose MetS were calculated. RESULTS: 28.6 % of men and 31.0 % of women had MetS in the Kazakh population. In men, WHtR had the highest AUC value 0.821, followed by BMI (0.801), TG/HDL-C (0.792), WHR (0.776) and BAI (0.666). In women, WHtR also had the highest AUC value (0.835), following by BMI (0.789), WHR (0.778), TG/HDL-C (0.778) and BAI (0.751). WHtR had the shortest ROC distance that was 0.37 and the optimal cutoff was 0.55 in men. In women, WHtR also had the shortest ROC distance of 0.35 and the optimal cutoff was 0.54. CONCLUSION: WHtR is the best predictor of MetS in both Kazakh men and women according to the IDF criteria. PMID- 27664084 TI - David Oliver: Reducing delays in hospitals. PMID- 27664083 TI - Composition and Chemical Variability of Cleistopholis patens Trunk Bark Oil from Cote d'Ivoire. AB - The chemical composition of trunk bark oil from Cleistopholis patens (Benth.) Engl. & Diels, growing wild in Cote d'Ivoire, has been investigated by GC (FID) in combination with retention indices, GC/MS and 13 C-NMR. Moreover, one oil sample has been subjected to CC and all the fractions analyzed by GC (RI) and 13 C-NMR. In total, 61 components have been identified, including various sesquiterpene esters scarcely found in essential oils. 13 C-NMR was particularly efficient for the identification of a component not eluted on GC and for the quantification of heat-sensitive compounds. Then, 36 oil samples, isolated from trunk bark harvested in six Ivoirian forests have been analyzed. The content of the main components varied drastically from sample to sample: (E)-beta caryophyllene (0.4 - 69.1%), beta-pinene (0 - 57%), alpha-phellandrene (0 - 33.2%), alpha-pinene (0.1 - 30.6%), beta-elemol (0.1 - 29.9%), germacrene D (0 - 25.4%), juvenile hormone III (0 - 22.9%), germacrene B (0 - 20.6%) and sabinene (tr-20.3%). Statistical analysis, hierarchical clustering and principal components analysis, carried out on the 36 compositions evidenced a fair chemical variability of the stem bark oil of this species. Indeed, three clusters have been distinguished: the composition of group I (ten samples) was dominated by beta-pinene and alpha-pinene, group II (nine samples) was represented by alpha phellandrene and p-cymene and group III (16 samples) by beta-elemol. A sample displayed an atypical composition dominated by (E)-beta-caryophyllene. PMID- 27664085 TI - Trends in Laboratory Rotavirus Detection: 2003 to 2014. AB - OBJECTIVES: We assessed the impact of rotavirus vaccination at national and state levels by evaluating the change in rotavirus antigen detection after vaccination licensure. We examined herd immunity in an unlikely vaccinated cohort and waning immunity with aging in a likely vaccinated cohort. We proposed a new approach to estimate the length of season by contrasting with what is recently reported by the Centers for Disease Control and Prevention. METHODS: We analyzed 11-year results of rotavirus testing (n = 276 342) conducted at Quest Diagnostics, a national clinical reference laboratory, spanning from September 2003 to August 2014. An enzyme immunoassay was used to test children's stool specimens for the presence of rotavirus antigen; results were reported as not detected or detected. RESULTS: Nationally, there was a significant reduction in the number of positive results (82.4%) and positivity rate (73.3%) after vaccination availability. The reductions were seen in all major states, although with geographic variability. The declining positivity rate in unlikely vaccinated children suggests herd immunity. Among those who were likely vaccinated, the positivity rate was higher in older children, indicating potential waning immunity with aging. Seasonal outbreaks continued in the postvaccine period, with peaks in alternating years. Seasons were longer in the postvaccine period than the prevaccine period. CONCLUSIONS: Our findings show a marked reduction in rotavirus detection throughout the nation after vaccine licensure, consistent with herd immunity. Postvaccine effectiveness may wane with aging. Seasons appear to be longer in the postvaccine period. PMID- 27664087 TI - Current Roles and Perceived Needs of Pediatric Hospital Medicine Fellowship Graduates. AB - OBJECTIVES: Pediatric hospitalists report the need for additional training in clinical and nonclinical domains. Pediatric hospital medicine (PHM) fellowships seek to provide this training and produce leaders in the field. Our objective is to describe current roles and perceived training needs of PHM fellowship graduates. METHODS: In 2014, all PHM fellowship graduates were asked to complete a Web-based survey. Survey questions addressed demographics, past training, current roles, and training needs in clinical care, research, education, and administration. Associations between fellowship experiences and outcomes were examined. RESULTS: Fifty-one of 61 eligible individuals completed the survey. Average duration as a pediatric hospitalist was 5 years. Ninety percent completed pediatric categorical residency, whereas 10% completed an Internal Medicine Pediatrics Residency. Most respondents completed a 1- (38%) or 2-year (46%) fellowship program. Ninety-six percent of respondents currently work in academic environments. The perceived need for additional clinical training was low, except procedures (44%). Nearly all teach medical students and pediatric residents, reporting adequate training in variety of teaching strategies. The majority of respondents conduct research, most commonly quality improvement (QI; 67%) and education (52%). Two-thirds are first authors on at least 1 peer-reviewed article. Research training needs include QI methodology (44%), biostatistics (43%), and obtaining funding (54%). A considerable number of respondents have academic leadership positions. CONCLUSIONS: PHM fellowship graduates are academic hospitalists with diverse responsibilities. Despite a short average career span, many have achieved leadership roles and been academically productive. Future curriculum development should focus on procedures, QI, and research training. PMID- 27664086 TI - Respiratory Morbidity After Childhood Burns: A 10-Year Follow-up Study. AB - BACKGROUND AND OBJECTIVE: The systemic responses triggered by burns and resuscitative measures may cause pulmonary damage and edema in the acute phase. These effects may occur in the absence of inhalation injury. Currently, there is a paucity of data on the recovery of the respiratory system postburn. This study aimed to examine 10-year hospital service use for respiratory morbidity in children with cutaneous burns and no smoke inhalation injury. METHODS: A population-based longitudinal study with 10-year follow-up using linked hospital and death from Western Australia for children <5 years when hospitalized for a first burn injury (n = 5290) between 1980 and 2012 and a frequency matched noninjury comparison cohort, randomly selected from Western Australia's birth registrations (n = 27 061). Multivariate negative binomial and Cox proportional hazards regression models were used to generate adjusted incidence rate ratios (IRR) and hazard ratios, respectively. RESULTS: After adjustment for demographic factors and preexisting health status, the burn cohort had higher rates of admissions for influenza and viral pneumonia (IRR, 1.78; 95% confidence interval [CI], 1.10-2.87), bacterial pneumonia (IRR, 1.34; 95% CI, 1.06-1.70), and other respiratory infections (IRR, 1.65; 95% CI, 1.43-1.90. No significant difference was found for other upper respiratory tract conditions (IRR, 1.10; 95% CI, 0.98 1.23) or chronic lower respiratory diseases (IRR, 0.99; 95% CI, 0.80-1.23) compared with the uninjured cohort. CONCLUSIONS: These findings demonstrated increased respiratory infection admissions after burns. These outcomes suggest that immune changes triggered by a burn injury may persist in some children for at least 10 years after wound healing. PMID- 27664088 TI - Water-Soluble Osmium Complexes Suitable for use in Luminescence-Based, Hydrogel Supported Sensors. AB - Osmium transition metal complexes are of particular interest in luminescence based sensing applications because of their longer wavelength absorptions and emissions, relative to similar ruthenium and rhenium complexes, that allow for inexpensive excitation and minimize interferences from autofluorescence when the sensor is used in biological samples. Reported here are the photophysical properties of a series of water-soluble osmium complexes suitable for use in hydrogel-based sensors: [Os(bpy)2(sulf-dpp)]Cl2, [Os(phen)2(sulf-dpp)]Cl2, [Os(dpp)2(sulf-dpp)]Cl2, and [Os(CO)2Cl2(sulf-dpp)], where bpy is 2,2' bipyridine, phen is 1,10-phenanthroline, dpp is 4,7-diphenyl-1,10-phenanthroline, and sulf-dpp is bathophenanthrolinedisulfonic acid disodium salt. The family of complexes showed minimal oxygen quenching, making them particularly well-suited for sensing applications in which oxygen concentration varies. Luminescence anisotropy was found to depend more significantly on net dipole moment than hydrodynamic radius of the molecule, and, as expected, excited state lifetime and luminescence anisotropy were highly dependent on the local environment of the reporter molecule. Results obtained for hydrogel-based relative humidity sensors containing [Os(CO)2Cl2(sulf-dpp)] and [Os(bpy)2(sulf-dpp)]Cl2 complexes highlight the significant potential for this class of compounds in a hydrogel-supported luminescence-based sensing approach. PMID- 27664089 TI - Pure motor hemiparesis due to occlusion of the internal carotid artery. PMID- 27664090 TI - Estimated serum vitamin D status, vitamin D intake, and risk of incident alopecia areata among US women. AB - Studies have identified increased prevalence of vitamin D deficiency in patients with alopecia areata (AA), an autoimmune disease characterized by hair loss, but none have prospectively examined vitamin D status and incident AA. In 55,929 women in the Nurses' Health Study (NHS), we prospectively evaluated the association between estimated vitamin D status, derived from a prediction model incorporating lifestyle determinants of serum vitamin D, and self-reported incident AA. We evaluated dietary, supplemental, and total vitamin D intake as additional exposures. Using Cox proportional hazards models, we calculated age adjusted and multivariate hazard ratios (HR) to evaluate risk of AA. We identified 133 cases of AA over a follow-up of 12 years. The age-adjusted HR between top vs. bottom quartiles for serum vitamin D score was 0.94 (95 % CI 0.60 1.48) and the corresponding multivariate HR was 1.08 (95 % CI 0.68-1.73). There was no significant association between dietary, supplemental, or total vitamin D intake and incident AA. This study does not support a preventive role for vitamin D in the risk of developing AA. PMID- 27664091 TI - Wide distribution range of rhizobial symbionts associated with pantropical sea dispersed legumes. AB - To understand the geographic distributions of rhizobia that associated with widely distributed wild legumes, 66 nodules obtained from 41 individuals including three sea-dispersed legumes (Vigna marina, Vigna luteola, and Canavalia rosea) distributed across the tropical and subtropical coastal regions of the world were studied. Partial sequences of 16S rRNA and nodC genes extracted from the nodules showed that only Bradyrhizobium and Sinorhizobium were associated with the pantropical legumes, and some of the symbiont strains were widely distributed over the Pacific. Horizontal gene transfer of nodulation genes were observed within the Bradyrhizobium and Sinorhizobium lineages. BLAST searches in GenBank also identified records of these strains from various legumes across the world, including crop species. However, one of the rhizobial strains was not found in GenBank, which implies the strain may have adapted to the littoral environment. Our results suggested that some rhizobia, which associate with the widespread sea-dispersed legume, distribute across a broad geographic range. By establishing symbiotic relationships with widely distributed rhizobia, the pantropical legumes may also be able to extend their range much further than other legume species. PMID- 27664092 TI - Novosphingobium profundi sp. nov. isolated from a deep-sea seamount. AB - A marine bacterial strain, F72T, was isolated from a solitary scleractinian coral, collected in Yap seamounts in the Pacific Ocean. Strain F72T is a Gram negative, light-yellow-pigmented, motile, rod-shaped bacterium. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain F72T is related to the genus Novosphingobium and has high 16S rRNA gene sequence similarities with the type strains of Novosphingobium pentaromativorans US6-1T (97.7 %), Novosphingobium panipatense SM16T (97.6 %), Novosphingobium mathurense SM117T (97.2 %) and Novosphingobium barchaimii LL02T (97.1 %). Ubiquinone Q-10 was detected as the dominant quinone. The predominant cellular fatty acids were C18:1omega7c and C17:1omega6c. The genomic DNA G+C content of strain F72T was 63.4 mol %. The polar lipids profile contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, sphingoglycolipid and one uncharacterized lipid. Strain F72T shared DNA relatedness of 25 % with N. pentaromativorans JCM 12182T, 31 % with N. panipatense DSM 22890T, 21 % with N. mathurense DSM 23374T and 26 % with N. barchaimii DSM 25411T. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that the strain F72T is a representative of a novel species of the genus Novosphingobium, for which we propose the name Novosphingobium profundi sp. nov. (type strain F72T = KACC 18566T = CGMCC 1.15390T). PMID- 27664093 TI - Smc5/6 complex regulates Sgs1 recombination functions. AB - The family of RecQ helicases is evolutionary conserved from bacteria to humans and play key roles in genome stability. The budding yeast RecQ helicase Sgs1 has been implicated in several key processes during the repair of DNA damage by homologous recombination as part of the STR complex (Sgs1-Top3-Rmi1). Limited information on how is Sgs1 recruited and regulated at sites of damage is available. Recently, we and others have uncover a direct link between the Smc5/6 complex and Sgs1. Most roles of Sgs1 during recombination, including DNA end resection, Holiday junction dissolution, and crossover suppression, are regulated through Mms21-dependent SUMOylation. Smc5/6 first acts as a recruiting platform for STR and then SUMOylates STR components to regulate their function. Importantly, the assembly of STR is totally independent of Smc5/6. Here, we provide a brief overview of STR regulation by Smc5/6. PMID- 27664094 TI - MicroRNA-463-3p/ABCG4: A new axis in glucose-stimulated insulin secretion. AB - OBJECTIVE: Glucose-stimulated insulin secretion (GSIS) is known to be essential in the control of metabolic fuel homeostasis, though the molecular mechanisms involved remain unclear. METHODS: MicroRNA (miRNA)-463-3p and ATP-binding cassette A4 (ABCG4) expression was analyzed by real-time PCR, and the potential role of miRNA-463-3p or ABCG4 was evaluated by overexpressing or silencing such miRNA or genes. RESULTS: The miRNA-463-3p inhibited GSIS without affecting cell viability. Further, mechanistic studies demonstrated that ABCG4 was a direct target of microRNA-463-3p and, to this effect, that ABCG4 played an important role in GSIS. The targeting was relevant in pancreatic islet beta-cells, where GSIS through the miRNA-463-3p/ABCG4 axis was observed. Interestingly, in type 2 diabetes human pancreatic islets, expression of miRNA-463-3p and insulin was upregulated and ABCG4 downregulated compared with nondiabetic controls, and their expression levels were closely correlated. CONCLUSIONS: The findings collectively establish a link between GSIS and the miRNA-463-3p/ABCG4 axis and represent a promising target for future diabetes mellitus treatments. PMID- 27664096 TI - Cross-reactions in specific Brachyspira spp. PCR assays caused by "Brachyspira hampsonii" isolates: implications for detection. AB - An emerging novel spirochete in swine, provisionally designated "Brachyspira hampsonii," has been detected worldwide. It has been associated with swine dysentery and cannot be differentiated from B. hyodysenteriae, the classical etiologic agent of this disease, using standard phenotypic methods. We evaluated cross-reactions of "B. hampsonii" isolates recovered from avian species in some of the currently available species-specific polymerase chain reaction (PCR) assays for the identification of swine Brachyspira species. Ten avian "B. hampsonii" isolates recovered from wild waterfowl were used. No false-positive results were recorded with a B. pilosicoli-specific PCR based on the amplification of a fragment of the 16S rRNA gene. However, the percentage of false-positive results varied, with a range of 10-80%, in the evaluated B. hyodysenteriae-specific assays based on the amplification of the 23S rRNA, nox, and tlyA genes. Similarly, results of the B. intermedia-specific PCR assays yielded poor specificity, with up to 80% of the "B. hampsonii" isolates tested giving false-positive results. Finally, 2 "B. hampsonii" avian isolates yielded a positive result in a B. innocens- and B. murdochii-specific PCR. This result should be interpreted very cautiously as these 2 isolates could represent a recombinant genotype. PMID- 27664095 TI - Impact of Intragastric Balloon Before Laparoscopic Gastric Bypass on Patients with Super Obesity: a Randomized Multicenter Study. AB - BACKGROUND: Super obese patients are recommended to lose weight before bariatric surgery. The effect of intragastric balloon (IGB)-induced weight loss before laparoscopic gastric bypass (LGBP) has not been reported. The aim of this prospective randomized multicenter study was to compare the impact of preoperative 6-month IGB with standard medical care (SMC) in LGBP patients. METHODS: Patients with BMI >45 kg/m2 selected for LGBP were included and randomized to receive either SMC or IGB. After 6 months (M6), the IGB was removed and LGBP was performed in both groups. Postoperative follow-up period was 6 months (M12). The primary endpoint was the proportion of patients requiring ICU stay >24 h; secondary criteria were weight changes, operative time, hospitalization stay, and perioperative complications. RESULTS: Only 115 patients were included (BMI 54.3 +/- 8.7 kg/m2), of which 55 underwent IGB insertion. The proportion of patients who stayed in ICU >24 h was similar in both groups (P = 0.87). At M6, weight loss was significantly greater in the IGB group than in the SMC group (P < 0.0001). Three severe complications occurred during IGB removal. Mean operative time for LGBP was similar in both groups (P = 0.49). Five patients had 1 or more surgical complications, all in the IGB group (P = 0.02). Both groups had similar hospitalization stay (P = 0.59) and weight loss at M12 (P = 0.31). CONCLUSION: IGB insertion before LGBP induced weight loss but did not improve the perioperative outcomes or affect postoperative weight loss. PMID- 27664097 TI - Elaeophora in the meninges of a Malayan sambar (Rusa unicolor equina). AB - An adult nematode was grossly identified in the meninges of a Malayan sambar (Rusa unicolor equina), with numerous microfilariae associated with encephalitis and vasculitis on histopathology. The nematode was confirmed to be Elaeophora schneideri by sequencing a portion of the 18S rRNA gene. Our report highlights the potential for aberrant migration of E. schneideri in exotic deer species and the use of advanced testing to specifically identify this metazoan parasite, avoiding misidentification of Parelaphostrongylus tenuis. PMID- 27664098 TI - Identification of Fusarium solani species complex from infected zebrafish (Danio rerio). AB - Although Fusarium sp. infections have been reported in aquatic invertebrates, studies of Fusarium spp. as fish pathogens remain very limited. In our study, a fungus was isolated from diseased zebrafish (Danio rerio). DNA sequence analysis of the fungus, based on a partial region of the translation elongation factor 1alpha gene (EF-1alpha), the internal transcribed spacer region and domains D1 and D2 of the large subunit of the ribosomal RNA gene (ITS plus LSU), and the RNA polymerase II subunit gene (RPB2), showed 99.9-100% homology to Fusarium solani species complex sequences. Multilocus sequence typing analysis based on 3-locus haplotypes (EF-1alpha, ITS plus LSU, and RPB2) suggests that the isolated strain was type 3+4-P. Challenge experiments showed that this organism could be pathogenic to zebrafish, but usually does not infect healthy subjects under normal circumstances. PMID- 27664100 TI - What volume of seeds can a chimpanzee carry in its body? AB - Great apes are important seed dispersers with large bodies, able to swallow large seeds and travel long distances. Although there have been several studies investigating seed dispersal quality [sensu Schupp (Vegetatio 107/108:15-29, 1993)] by chimpanzees, there is little information on the volume of seeds they can carry in their bodies. When a relatively fresh corpse of a mature female chimpanzee was found at Mahale, Tanzania, we took advantage of the rare opportunity to investigate the total weight and cubic volume of seeds recovered from the corpse. The seeds contained in the corpse weighed 258.8 g (dry weight) and measured 489.4 cm3. The volume of seeds was 14.7 % of the previously reported capacity of the digestive tract of a chimpanzee in captivity. We also indirectly estimated the volume of seeds from the values of observed seed volume in feces, the reported number of defecations per day, and the seed passage time. The estimated volume was significantly lower than the observed seed volume, suggesting that the number of defecations per day is underestimated because it may not include nighttime defecation. PMID- 27664099 TI - The bacteriophage-derived transcriptional regulator, LscR, activates the expression of levansucrase genes in Pseudomonas syringae. AB - Synthesis of the exopolysaccharide levan occurs in the bacterial blight pathogen of soybean, Pseudomonas syringae pv. glycinea PG4180, when this bacterium encounters moderate to high concentrations of sucrose inside its host plant. The process is mediated by the temperature-dependent expression and secretion of two levansucrases, LscB and LscC. Previous studies showed the importance of a prophage-associated promoter element in driving the expression of levansucrase genes. Herein, heterologous screening for transcriptional activators revealed that the prophage-borne transcriptional regulator, LscR, from P. syringae mediates expression of levansucrase. A lscR-deficient mutant was generated and exhibited a levan-negative phenotype when grown on a sucrose-rich medium. This phenotype was confirmed by zymographic analysis and Western blots which demonstrated absence of levansucrase in the supernatant and total cell lysates. Transcriptional analysis showed a down-regulation of expression levels of levansucrase and glycosyl hydrolase genes in the lscR-deficient mutant. Ultimately, a direct binding of LscR to the promoter region of levansucrase was demonstrated using electrophoretic mobility shift assays allowing to conclude that a bacteriophage-derived regulator dictates expression of bacterial genes involved in in planta fitness. PMID- 27664101 TI - Natural course of mild Graves' orbitopathy: is it a chronic remitting or a transient disease? AB - BACKGROUND/AIMS: The natural course of Graves' orbitopathy (GO) has been poorly documented. The aim of this review is to provide current knowledge regarding the natural course of mild GO, trying to address the issue of whether and to what extent it constitutes a chronic remitting or transient disease. METHODS: We systematically searched PubMed for English language publications until August 2016 under the following terms: "Graves' orbitopathy" OR "Graves' ophthalmopathy" OR "thyroid eye disease" AND "natural course" OR "natural history". RESULTS: Few studies have investigated the course of mild orbital disease in patients with GO. Large controlled trials are lacking and data can be extracted mainly from small retrospective and some prospective studies, after excluding patients who had received radioiodine for thyrotoxicosis or surgical treatment for GO. In general, more than half of GO patients may show spontaneous improvement in their clinical features, whereas no safe conclusions can be drawn with regard to complete resolution, with percentages ranging from 6 to 58 %. CONCLUSIONS: The question whether mild GO is a remitting, albeit chronic disease, or even a transient event in the course of Graves' disease, remains currently unanswered. PMID- 27664103 TI - Development of a mother and baby unit contraception assessment tool. AB - Unplanned pregnancies are a unique, yet significant risk factor in perinatal mental health. Our aim was to create an assessment tool to assess mother's views on contraception as part of the discharge planning process. We used a quantitative-qualitative approach. A clinician-guided questionnaire was completed by patients prior to their discharge from hospital and analysed using Microsoft Excel. Semi-structured interviews were used to explore views regarding family planning in greater depth. Interviews were recorded and transcribed verbatim onto Microsoft Word. Emerging themes were identified using a grounded theory thematic analysis approach. Eighteen inpatients were assessed at the Bethlem Mother and Baby Unit over a 4-month period (May-August 2015). Half of the women stated that the pregnancy was unplanned. The most common contraception methods used were condoms, followed by no method/natural cycle technique. Forty-four percent felt unsure of contraception options available and were keen for further advice and referral to family planning services. Interestingly, almost all the women interviewed stated that their experience of perinatal mental illness had changed their views on having more children. The contraception assessment tool is a short, simple questionnaire that can be adopted across inpatient and community settings. In cooperating family, planning into the discharge care plan could be protective in preventing future unplanned pregnancies in women at high risk of perinatal mental illness relapse. Performing the assessment also provided an added opportunity for psycho-education regarding reproductive health and medication use during the perinatal period. The tool also encouraged liaison with GPs and local family planning services. PMID- 27664102 TI - Follicular fluid PlGF/sFlt-1 ratio and soluble receptor for advanced glycation end-products correlate with ovarian sensitivity index in women undergoing A.R.T. AB - PURPOSE: Considering potential roles of soluble receptor for advanced glycation end products (sRAGE) and placental growth factor (PlGF) in ovarian function and embryo implantation, in the present study we have evaluated the association of these factors and also PlGF/sFlt-1 ratio with the ovarian response and implantation rate by dividing patients according to the OSI. METHODS: In a cross sectional study, 90 infertile women who were undergoing ICSI cycle using long protocol were recruited. The patients were divided according to ovarian sensitivity index (OSI). ICSI cycle outcomes were evaluated for each patient and PlGF, sFlt-1 and sRAGE levels of follicular fluid were assayed using commercial ELISA kits. RESULTS: Follicular fluid (FF) sRAGE levels and PlGF/sFlt-1 ratio were statistically greater in high-responder women than other responders (p < 0.05). Positive correlations were obtained between sRAGE level with the number of oocytes, follicles and OSI level. sRAGE levels with cutoff value of 4.83 (ng/ml) for evaluating the pregnancy outcome showed 81.8 % sensitivity and 60.7 % specificity. Furthermore, there were positive associations between PlGF/sFlt-1 ratio with the number of oocytes, embryos and OSI level. CONCLUSION: In conclusion, the results of current study supported that good ovarian response is independent of pregnancy outcome. Our results showed that FF levels of sRAGE and PlGF/sFlt-1 ratio could be used as markers for determining the high-responder women. Also, FF sRAGE levels could be a good predictor for ART outcome. PMID- 27664105 TI - Autologous intrauterine transfusion in a case of anti-U. AB - BACKGROUND: Minor red blood cell antibodies are becoming a more common cause of hemolytic disease of the newborn. Anti-U are a rare alloantibody found almost exclusively in people of black descent. There is limited experience to guide the management of pregnancies complicated by anti-U. Furthermore, there is often no suitable cross-matched blood available for transfusion of a patient with anti-U. CASE REPORT: A 21-year-old P0G1 presented at 25 weeks' gestation with D- disease in pregnancy. She had a significant indirect antiglobulin test titer of 512. Anti U were identified and no suitable cross-matched blood was available. Maternal blood was prepared for autologous intrauterine fetal transfusion. Two such transfusions were performed. RESULTS: A healthy fetus delivered at 32 weeks that did not require phototherapy or an exchange transfusion. CONCLUSION: Autologous transfusion of prepared maternal blood provides a safe option for intrauterine fetal therapy in pregnancies complicated by rare alloantibodies. PMID- 27664104 TI - Association of physical activity and sedentary behavior with depression and anxiety symptoms during pregnancy in a multiethnic cohort of Asian women. AB - OBJECTIVES: This study aimed to investigate associations of physical activity (PA) and sedentary behavior (SB) with depression and anxiety symptoms during pregnancy among Chinese, Malay, and Indian women. METHODS: Women answered PA and SB (sitting time and television time) interview questions and self-completed the Edinburgh Postnatal Depression Scale (EPDS) and State-Trait Anxiety Inventory (STAI) questionnaires, at week 26-28 gestation. Sufficient levels of PA (>=600MET minutes/week) and higher sitting time (>=7 h/day) were determined. Associations of PA and SB with probable antenatal depression (EPDS-score >=15), higher state anxiety (score >=42), and higher trait anxiety (score >=43) were determined by logistic regression analysis. RESULTS: Among the 1144 pregnant women included in the study, 7.3, 22.5, and 23.6 % had probable antenatal depression, higher state anxiety, and higher trait anxiety symptoms, respectively. In the adjusted models, women with sufficient level of PA were less likely to have probable antenatal depression (OR 0.54, 95 % CI 0.31-0.94, p = 0.030) and higher trait anxiety symptoms (OR 0.68, 95 % CI 0.48-0.94, p = 0.022). PA was not associated with state anxiety symptoms. SB was not associated with any of the investigated outcomes. CONCLUSIONS: Sufficient PA was associated with a reduced likelihood of probable antenatal depression and trait anxiety symptoms. Further investigation of these findings is warranted to determine cause-effect relationships and identify potential preventive strategies. PMID- 27664108 TI - Cost-Effectiveness of High Dose Hemodialysis in Comparison to Conventional In Center Hemodialysis in the Netherlands. AB - INTRODUCTION: In the Netherlands, the current standard of care for treating patients with end-stage renal disease is three sessions of in-center hemodialysis (conventional ICHD). However, the literature indicates that high dose hemodialysis (high dose HD) may provide better health outcome such as survival and quality of life. The objective of this study was to determine the cost effectiveness of high dose HD, both in-center and at home, in comparison to conventional ICHD from a Dutch payer's perspective over a 5 year period. Additionally, the cost-effectiveness of conventional HD at home in comparison to conventional ICHD will be analysed. METHODS: A Markov model was developed assuming 28-day treatment cycles and was populated with data from Dutch and international renal registries, official tariffs and medical literature. Univariable and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Using publicly available tariffs from the Dutch Healthcare Authority (Nederlandse Zorgautoriteit) of 2015, doing high dose ICHD instead of conventional ICHD shows an incremental cost-effectiveness ratio (ICER) of ?275,747 per quality-adjusted life year (QALY) gained. In contrast, the ICER of high dose HD at home in comparison to conventional ICHD is ?3248 per gained QALY. The final analysis shows that conventional HD at home is less costly per patient (-?3063) than conventional ICHD and results in health benefit improvement (+0.249 QALYs), and is therefore regarded as cost saving. CONCLUSION: Treating dialysis patients with conventional HD at home shows to be cost saving in comparison to conventional ICHD. However, the magnitude of clinical benefit of high dose HD at home is over two times greater than the clinical benefit of conventional HD at home. According to our analysis, from a payer's perspective, high dose HD should be offered as a home therapy to obtain its clinical benefits in a cost-effective manner. Future research should consider our findings alongside societal factors, such as patient preference, monitoring cost for the home patient, productivity loss and capacity. FUNDING: Baxter BV, The Netherlands. PMID- 27664106 TI - Diagnostic Values and Limitations of (1,3)-beta-D-Glucans and Galactomannan Assays for Invasive Fungal Infection in Patients Admitted to Pediatric Intensive Care Unit. AB - The relationship among (1,3)-beta-D-glucans (BG), galactomannan (GM), and the risk of developing invasive fungal infections (IFI) has been observed in adult ICU and in children with hematological malignancies. Only scant data evaluated the value of BG/GM assays for diagnosis of IFI in patients with nonhematological diseases in pediatric intensive care unit (PICU). In this study, we assessed the diagnostic value of these markers for IFI in PICU. The records of 230 patients were retrospectively evaluated. Out of 117 patients (7 proven, 23 probable, and 87 cases without evidence of IFI) performed GM and BG assays. The results showed many factors were associated with false-positive test results. Patients who aged over 3 years had higher levels of GM and BG than younger infants. The levels of BG were higher in subjects with dairy, human blood products, antibiotics, and corticosteroids therapy than in cases without these treatments. Unlike BG assay, GM assay was less susceptible to above-mentioned factors expect blood products. The levels of BG and GM in IFI cases were dramatically higher than in controls. The diagnostic performance of these assays showed that GM assay had better results when compared with BG assay. On the whole, negative predictive value in both GM and BG assays was dramatically higher than other diagnostic parameters. In conclusion, BG assay was highly susceptible to many factors, and GM assay could be useful for diagnosis of IFI for its high sensitivity, but the over benefit of this assay limited in its inadequate specificity. The comparative advantage of BG and BG assays lied in excluding IFI in non-hematological PICU patients. PMID- 27664107 TI - A Retrospective Claims Database Study on Drug Utilization in Japanese Patients with Crohn's Disease Treated with Adalimumab or Infliximab. AB - INTRODUCTION: Crohn's disease (CD) is a chronic and progressive disease in which the long-term management is important. This study sought to assess treatment persistence and dose escalation in the maintenance phase with adalimumab (ADA) or infliximab (IFX) in a Japanese real-world setting. METHODS: A retrospective analysis was conducted using the Japan Medical Data Center database. CD patients with either ADA or IFX prescriptions between January 2012 and February 2015 were included. Outcomes of interest were (1) failure in the induction phase (defined as switch or discontinuation) and (2) persistence in the maintenance phase (defined as the absence of switch or discontinuation over 12 months since maintenance initiation). RESULTS: Overall, 133 patients (53 ADA; 80 IFX) were included. Of them, treatment failed in 26 patients (19.6%) in the induction phase. During the induction phase, there was a trend towards fewer treatment failures with ADA than IFX (88.7% vs. 75.0%; p = 0.051). Of those who completed induction, 64 patients (33 ADA; 31 IFX) had at least 12 months of valid insurance enrolment after the initiation of maintenance and 13 (5 ADA; 8 IFX) had either switch or discontinuation within 12 months after the initiation of maintenance. Probabilities of switch or discontinuation over 12 months after the maintenance date were 15.2% and 20.9% for ADA and IFX groups, respectively (p-log rank = 0.7764). CONCLUSION: Japanese patients have a high primary response to anti-tumor necrosis factor therapy in the real-world setting, in line with the results of clinical trials. This initial therapeutic advantage can be lost during the maintenance phase, leading to dose escalation, treatment switch, or discontinuation. This study suggests that those events occurred in comparable proportions of patients treated with either ADA or IFX. However, these findings should be considered with caution given the retrospective nature and small size of the study. FUNDING: Abbvie GK, Tokyo, Japan. PMID- 27664109 TI - A Review of Daclatasvir Drug-Drug Interactions. AB - : The treatment of hepatitis C virus (HCV) infection has been revolutionized in recent years by the development of direct-acting antiviral regimens that do not contain peginterferon (pegIFN) and/or ribavirin (RBV). While direct-acting antiviral-based regimens have been shown to be greatly superior to pegIFN/RBV based regimens in terms of efficacy and safety, they have a greater susceptibility to drug-drug interactions (DDIs). Daclatasvir (DCV)-the benchmark pangenotypic nonstructural protein 5A inhibitor-has been shown to be efficacious and generally well tolerated in partnership with other HCV direct-acting antivirals, including sofosbuvir, asunaprevir (ASV), and ASV plus beclabuvir. DCV may be the object of a DDI via the induction or inhibition of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) by the concomitant medication, or the precipitant of a DDI via DCV-based induction/inhibition of CYP 3A4 or inhibition of P-gp, organic anion transporting polypeptide 1B1/B3, and/or breast cancer resistance protein. This article presents an overview of the drug interaction studies conducted during the clinical development of DCV, the findings of these studies that led to the guidance on concomitant medication use and dosage along with any required DCV dose modifications, and the use of the known metabolic pathway of DCV to guide concomitant dosing where direct drug-drug studies have not been conducted. The robust characterization of the DCV clinical pharmacology program has demonstrated that DCV has few or no clinically relevant DDIs with medications with which it is likely to be co-administered, and the majority of DDIs that do occur can be predicted and easily managed. FUNDING: Bristol-Myers Squibb. PMID- 27664110 TI - Loss of Msp1p in Schizosaccharomyces pombe induces a ROS-dependent nuclear mutator phenotype that affects mitochondrial fission genes. AB - Mitochondria continually fuse and divide to dynamically adapt to changes in metabolism and stress. Mitochondrial dynamics are also required for mitochondrial DNA (mtDNA) integrity; however, the underlying reason is not known. In this study, we examined the link between mitochondrial fusion and mtDNA maintenance in Schizosaccharomyces pombe, which cannot survive without mtDNA, by screening for suppressors of the lethality induced by loss of the dynamin-related large GTPase Msp1p. Our findings reveal that inactivation of Msp1p induces a ROS-dependent nuclear mutator phenotype that affects mitochondrial fission genes involved in suppressing mitochondrial fragmentation and mtDNA depletion. This indicates that mitochondrial fusion is crucial for maintaining the integrity of both mitochondrial and nuclear genetic information. Furthermore, our study suggests that the primary roles of Msp1p are to organize mitochondrial membranes, thus making them competent for fusion, and maintain the integrity of mtDNA. PMID- 27664112 TI - Plasma levels of trastuzumab in gastric cancer: Case report. AB - Introduction The use of trastuzumab with a fluoropyrimidine and platinum compound is currently the standard first-line treatment of patients with metastatic HER2 positive gastric cancer, but it appears that serum levels of trastuzumab determine the clinical effectiveness of this treatment, affecting progression free survival and overall survival. Case report We report the case of a patient with metastatic HER2-positivegastric cancer, receiving XELOX (fluoropyrimidine and oxaliplatin) plus trastuzumab at standard doses, who presented sub therapeutic serum levels during the first two treatment cycles and rapid disease progression (progression-free survival = 5.6 months). Discussion This case reveals a possible cause of poor effectiveness of trastuzumab treatment for metastatic gastric cancer in some patients, namely low circulating levels of the drug. It highlights the importance of monitoring as a possible tool for individual dose adjustment to optimize this therapy. PMID- 27664111 TI - Electro-physiological changes in the brain induced by caffeine or glucose nasal spray. AB - OBJECTIVE: A direct link between the mouth cavity and the brain for glucose (GLUC) and caffeine (CAF) has been established. The aim of this study is to determine whether a direct link for both substrates also exist between the nasal cavity and the brain. METHODS: Ten healthy male subjects (age 22 +/- 1 years) performed three experimental trials, separated by at least 2 days. Each trial included a 20-s nasal spray (NAS) period in which solutions placebo (PLAC), GLUC, or CAF were provided in a double-blind, randomized order. During each trial, four cognitive Stroop tasks were performed: two familiarization trials and one pre- and one post-NAS trial. Reaction times and accuracy for different stimuli (neutral, NEUTR; congruent, CON; incongruent INCON) were determined. Electroencephalography was continuously measured throughout the trials. During the Stroop tasks pre- and post-NAS, the P300 was assessed and during NAS, source localization was performed using standardized low-resolution brain electromagnetic tomography (sLORETA). RESULTS AND DISCUSSION: NAS activated the anterior cingulate cortex (ACC). CAF-NAS also increased theta and beta activity in frontal cortices. Furthermore, GLUC-NAS increased the beta activity within the insula. GLUC-NAS also increased the P300 amplitude with INCON (P = 0.046) and reduced P300 amplitude at F3-F4 and P300 latency at CP1-CP2-Cz with NEUTR (P = 0.001 and P = 0.016, respectively). The existence of nasal bitter and sweet taste receptors possibly induce these brain responses. CONCLUSION: Greater cognitive efficiency was observed with GLUC-NAS. CAF-NAS activated cingulate, insular, and sensorymotor cortices, whereas GLUC-NAS activated sensory, cingulate, and insular cortices. However, no effect on the Stroop task was found. PMID- 27664113 TI - An Exercise in Extrapolation: Clinical Management of Atypical CML, MDS/MPN Unclassifiable, and MDS/MPN-RS-T. AB - According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification. In this review, we focus on biology and management of aCML, MDS/MPN-U, and MDS/MPN-RS-T. There is considerable overlap between these entities which we attempt to further elucidate in this review. We also discuss recent advances in the field of molecular landscape that further defines and characterizes this heterogeneous group of disorders. The paucity of clinical trials available secondary to unclear pathogenesis and rarity of these diseases makes the management of these entities clinically challenging. This review summarizes some of the current knowledge of the molecular pathogenesis and suggested treatment guidelines based on the available data. PMID- 27664116 TI - On the relationship between medical ethics and medical professionalism. PMID- 27664114 TI - Computational imaging analysis of fibrin matrices with the inclusion of erythrocytes from homozygous SS blood reveals agglomerated and amorphous structures. AB - Sickle cell disease is a single point mutation disease that is known to alter the coagulation system, leading to hypercoagulable plasma conditions. These hypercoagulable conditions can lead to complications in the vasculature, caused by fibrin clots that form undesirably. There is a need to understand the morphology and structure of fibrin clots from patients with sickle cell disease, as this could lead to further discovery of treatments and life-saving therapies. In this work, a computational imaging analysis method is presented to evaluate fibrin agglomeration in the presence of erythrocytes (RBCs) homozygous for the sickle cell mutation (SS). Numerical algorithms were used to determine agglomeration of fibrin fibers within a matrix with SS RBCs to test the hypothesis that fibrin matrices with the inclusion of SS RBCs possess a more agglomerated structure than native fibrin matrices with AA RBCs. The numerical results showed that fibrin structures with SS RBCs displayed an overall higher degree of agglomeration as compared to native fibrin structures. The computational algorithm was also used to evaluate fibrin fiber overlap (aggregation) and anisotropy (orientation) in normal fibrin matrices compared to fibrin matrices polymerized around SS RBCs; however, there was no statistical difference. Ultrasound measurements of stiffness revealed rigid RBCs in the case of samples derived from homozygous SS blood, and densely evolving matrices, when compared to normal fibrin with the inclusion of AA RBCs. An agglomeration model is suggested to quantify the fibrin aggregation/clustering near RBCs for both normal fibrin matrices and for the altered structures. The results of this work are important in the sense that the understanding of aggregation and morphology in fibrin clots with incorporation of RBCs from persons living with sickle cell anemia may elucidate the complexities of comorbidities and other disease complications. PMID- 27664117 TI - Report from the national data guardian for health and care. PMID- 27664118 TI - Two-phase vesicles: a study on evolutionary and stationary models. AB - In the current article, the dynamic evolution of two-phase vesicles is presented as an extension to a previous stationary model and based on an equilibrium of local forces. In the simplified model, ignoring the effects of membrane inertia, a dynamic equilibrium between the membrane bending potential and local fluid friction is considered in each phase. The equilibrium equations at the domain borders are completed by extended introduction of membrane section reactions. We show that in some cases, the results of stationary and evolutionary models are in agreement with each other and also with experimental observations, while in others the two models differ markedly. The value of our approach is that we can account for unresponsive points of uncertainty using our equations with the local velocity of the lipid membranes and calculating the intermediate states (shapes) in the consequent evolutionary, or response, path. PMID- 27664119 TI - Structural and functional alterations in the prefrontal cortex after post-weaning social isolation: relationship with species-typical and deviant aggression. AB - Although the inhibitory control of aggression by the prefrontal cortex (PFC) is the cornerstone of current theories of aggression control, a number of human and laboratory studies showed that the execution of aggression increases PFC activity; moreover, enhanced activation was observed in aggression-related psychopathologies and laboratory models of abnormal aggression. Here, we investigated these apparently contradictory findings in the post-weaning social isolation paradigm (PWSI), an established laboratory model of abnormal aggression. When studied in the resident-intruder test as adults, rats submitted to PWSI showed increased attack counts, increased share of bites directed towards vulnerable body parts of opponents (head, throat, and belly) and reduced social signaling of attacks. These deviations from species-typical behavioral characteristics were associated with a specific reduction in the thickness of the right medial PFC (mPFC), a bilateral decrease in dendritic and glial density, and reduced vascularization on the right-hand side of the mPFC. Thus, the early stressor interfered with mPFC development. Despite these structural deficits, aggressive encounters enhanced the activation of the mPFC in PWSI rats as compared to controls. A voxel-like functional analysis revealed that overactivation was restricted to a circumscribed sub-region, which contributed to the activation of hypothalamic centers involved in the initiation of biting attacks as shown by structural equation modeling. These findings demonstrate that structural alterations and functional hyperactivity can coexist in the mPFC of rats exposed to early stressors, and suggest that the role of the mPFC in aggression control is more complex than suggested by the inhibitory control theory. PMID- 27664120 TI - Reduced DNA methylation of FKBP5 in Cushing's syndrome. AB - FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing's syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients. PMID- 27664122 TI - Organizational Capabilities for Integrating Care: A Review of Measurement Tools. AB - The success of integrated care interventions is highly dependent on the internal and collective capabilities of the organizations in which they are implemented. Yet, organizational capabilities are rarely described, understood, or measured with sufficient depth and breadth in empirical studies or in practice. Assessing these capabilities can contribute to understanding why some integrated care interventions are more effective than others. We identified, organized, and assessed survey instruments that measure the internal and collective organizational capabilities required for integrated care delivery. We conducted an expert consultation and searched Medline and Google Scholar databases for survey instruments measuring factors outlined in the Context and Capabilities for Integrating Care Framework. A total of 58 instruments were included in the review and assessed based on their psychometric properties, practical considerations, and applicability to integrated care efforts. This study provides a bank of psychometrically sound instruments for describing and comparing organizational capabilities. Greater use of these instruments across integrated care interventions and studies can enhance standardized comparative analyses and inform change management. Further research is needed to build an evidence base for these instruments and to explore the associations between organizational capabilities and integrated care processes and outcomes. PMID- 27664121 TI - Molecular insights into substrate recognition and catalytic mechanism of the chaperone and FKBP peptidyl-prolyl isomerase SlyD. AB - BACKGROUND: Peptidyl-prolyl isomerases (PPIases) catalyze cis/trans isomerization of peptidyl-prolyl bonds, which is often rate-limiting for protein folding. SlyD is a two-domain enzyme containing both a PPIase FK506-binding protein (FKBP) domain and an insert-in-flap (IF) chaperone domain. To date, the interactions of these domains with unfolded proteins have remained rather obscure, with structural information on binding to the FKBP domain being limited to complexes involving various inhibitor compounds or a chemically modified tetrapeptide. RESULTS: We have characterized the binding of 15-residue-long unmodified peptides to SlyD from Thermus thermophilus (TtSlyD) in terms of binding thermodynamics and enzyme kinetics through the use of isothermal titration calorimetry, nuclear magnetic resonance spectroscopy, and site-directed mutagenesis. We show that the affinities and enzymatic activity of TtSlyD towards these peptides are much higher than for the chemically modified tetrapeptides that are typically used for activity measurements on FKBPs. In addition, we present a series of crystal structures of TtSlyD with the inhibitor FK506 bound to the FKBP domain, and with 15-residue-long peptides bound to either one or both domains, which reveals that substrates bind in a highly adaptable fashion to the IF domain through beta strand augmentation, and can bind to the FKBP domain as both types VIa1 and VIb like cis-proline beta-turns. Our results furthermore provide important clues to the catalytic mechanism and support the notion of inter-domain cross talk. CONCLUSIONS: We found that 15-residue-long unmodified peptides can serve as better substrate mimics for the IF and FKBP domains than chemically modified tetrapeptides. We furthermore show how such peptides are recognized by each of these domains in TtSlyD, and propose a novel general model for the catalytic mechanism of FKBPs that involves C-terminal rotation around the peptidyl-prolyl bond mediated by stabilization of the twisted transition state in the hydrophobic binding site. PMID- 27664123 TI - Trends in the use of oral contraceptives among adolescents and young women in Spain. AB - BACKGROUND: We aimed to determine the prevalence of consumption of oral contraceptives (OCs) among adolescents and young women living in Spain and to identify the factors associated with this consumption. METHODS: We performed a cross-sectional study on the consumption of OCs by women aged 15-30 years residing in Spain. We used secondary individualized data from the 2006 (n = 2513) and 2012 (n = 1530) Spanish National Health Surveys. The dependent variable was the use of OCs in the previous 2 weeks. Independent variables included sociodemographic characteristics, comorbidity, lifestyle, and healthcare resource utilization. The prevalence of OC consumption was analysed by investigating the changes observed between 2006 and 2012. We used multivariate logistic regression to identify the independent factors associated with OC use in each year. RESULTS: In 2006, 14.42 % of women reported using OCs; this percentage dropped to 10.21 % in 2012 (p < 0.05). Multivariate analysis revealed an association between OC use and visits to the gynaecologist (AOR, 5.60 [95 % CI, 2.93-10.73] in 2006; and AOR, 3.55 [95 % CI, 1.30-9.73] in 2012), Pap smear tests (AOR, 1.8 [95 % CI, 1.23 2.87] in 2006; and AOR, 2.42 [95 % CI, 1.30-4.51] in 2012), and smoking in 2006 (AOR, 1.42 [95 % CI, 1.04-1.93]). CONCLUSIONS: There was a significant decrease in OC use from 2006 to 2012 among adolescents and young women living in Spain. In the present study, consumers of OCs were women who visited a gynaecologist more often and complied more with preventive measures such as Pap smear testing. Also, women who reported having used OCs were more likely to smoke than the rest of the study population, although the smoking habit is a risk factor for thrombotic events in women who take OCs. PMID- 27664124 TI - Description and initial evaluation of incorporating electronic follow-up of study participants in a longstanding multisite cohort study. AB - BACKGROUND: The objective of this study was to evaluate a pilot program that allowed Chicago field center participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study to submit follow-up information electronically (eCARDIA). METHODS: Chicago field center participants who provided email addresses were invited to complete contact information and follow-up questionnaires on medical conditions electronically in 2012-2013. Sociodemographic characteristics were compared between those who did and did not complete follow-up electronically. The number of participant contacts by CARDIA staff needed before follow-up was completed was also evaluated. RESULTS: Blacks and low socioeconomic position individuals were less likely to complete follow-up using the electronic questionnaire. Participants who used the electronic questionnaire for follow-up needed fewer contacts (e.g., median 1 contact compared with 3for contact information follow-up), but they also needed fewer contacts prior to eCARDIA (median 1 before and after eCARDIA). CONCLUSIONS: Findings suggest other approaches will be needed to maintain contact and elicit follow-up information from harder-to-reach individuals. PMID- 27664126 TI - Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy. AB - BACKGROUND: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. METHODS: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. RESULTS: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status >= 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. CONCLUSION: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions. PMID- 27664125 TI - Adult ADHD and Comorbid Somatic Disease: A Systematic Literature Review. AB - OBJECTIVE: To systematically review, synthesize, and appraise available evidence, connecting adult ADHD with somatic disease. METHOD: Embase, Psychinfo, and Medline databases were searched for studies published from 1994 to 2015 addressing adult ADHD and somatic comorbidity. Somatic conditions were classified according to International Classification of Diseases (ICD-10) codes. Levels of evidence were graded as inconclusive, tentative, or well documented. RESULTS: Most of the 126 studies included in the qualitative synthesis were small and of modest quality. Obesity, sleep disorders, and asthma were well-documented comorbidities in adult ADHD. Tentative evidence was found for an association between adult ADHD and migraine and celiac disease. In a large health registry study, cardiovascular disease was not associated with adult ADHD. CONCLUSION: There are few large systematic studies using standardized diagnostic criteria evaluating adult ADHD and somatic comorbidities. Significant associations are found between adult ADHD and several somatic diseases, and these are important to consider when assessing and treating either adult ADHD or the somatic diseases. PMID- 27664128 TI - Erratum to: 'Integrating evidence-based practices for increasing cancer screenings in safety net health systems: a multiple case study using the Consolidated Framework for Implementation Research'. PMID- 27664129 TI - A randomized, double-blind, placebo-controlled clinical trial of fluoride varnish in preventing dental caries of Sjogren's syndrome patients. AB - BACKGROUND: Sjogren's syndrome (SS) patients are prone to caries development due to reduction of salivary flow. Topical fluoride is commonly prescribed for caries prevention. METHODS: In this 24-month randomized, double-blind, placebo controlled clinical trial, SS patients were randomly assigned to receive either fluoride varnish or placebo gel quarterly. Development and arrest of caries at the coronal and root surfaces were recorded at 12-month and 24-month and compared to that of the baseline. Effect of fluoride varnish on oral Candida and lactobacilli colonization was explored by comparing baseline oral microbiological assessments to data obtained at 12-month and 24-month. RESULTS: Seventy-eight SS patients (mean age = 50 years, 2 men) completed this trial. At 24-month, the mean new coronal enamel caries were 1.6 surfaces in both groups, and new dentin caries were 1.4 and 2.7 surfaces in the fluoride and placebo group respectively (p > 0.05). Mean arrested caries were 0.6 and 0.7 surfaces for fluoride and placebo groups respectively and that of root caries were 0.3 and 0.1 surfaces (p > 0.05). The mean oral Candida count was reduced by 30 % in the fluoride group but increased 61 % in the placebo group while no change in oral lactobacilli counts in both groups at 24 months (p > 0.05). SS patients receiving fluoride varnish were significantly less likely to develop dentin caries (p < 0.05). In contrast, those with high baseline DMFS scores (p = 0.05), harbored mixed Candida species (p < 0.05), or unstimulated whole saliva at low pH (p < 0.01) were significantly more likely to develop dentin caries. CONCLUSIONS: Results of this randomized clinical trial did not provide clear evidence to support or refute that quarterly applications of fluoride varnish can prevent development of dental caries in people with Sjogren's syndrome. TRIAL REGISTRATION: This study was retrospectively registered at the ISRCTN registry ( ISRCTN85164658 ) on 9 Sept 2016 and was funded by the Research Grant Council of Hong Kong. PMID- 27664127 TI - Arbovirosis and potential transmission blocking vaccines. AB - Infectious diseases caused by arboviruses (viruses transmitted by arthropods) are undergoing unprecedented epidemic activity and geographic expansion. With the recent introduction of West Nile virus (1999), chikungunya virus (2013) and Zika virus (2015) to the Americas, stopping or even preventing the expansion of viruses into susceptible populations is an increasing concern. With a few exceptions, available vaccines protecting against arboviral infections are nonexistent and current disease prevention relies on vector control interventions. However, due to the emergence of and rapidly spreading insecticide resistance, different disease control methods are needed. A feasible method of reducing emerging tropical diseases is the implementation of vaccines that prevent or decrease viral infection in the vector. These vaccines are designated 'transmission blocking vaccines', or TBVs. Here, we summarize previous TBV work, discuss current research on arboviral TBVs and present several promising TBV candidates. PMID- 27664132 TI - CCGs to get L6 a patient to extend general practice opening hours. PMID- 27664130 TI - The environment ontology in 2016: bridging domains with increased scope, semantic density, and interoperation. AB - BACKGROUND: The Environment Ontology (ENVO; http://www.environmentontology.org/ ), first described in 2013, is a resource and research target for the semantically controlled description of environmental entities. The ontology's initial aim was the representation of the biomes, environmental features, and environmental materials pertinent to genomic and microbiome-related investigations. However, the need for environmental semantics is common to a multitude of fields, and ENVO's use has steadily grown since its initial description. We have thus expanded, enhanced, and generalised the ontology to support its increasingly diverse applications. METHODS: We have updated our development suite to promote expressivity, consistency, and speed: we now develop ENVO in the Web Ontology Language (OWL) and employ templating methods to accelerate class creation. We have also taken steps to better align ENVO with the Open Biological and Biomedical Ontologies (OBO) Foundry principles and interoperate with existing OBO ontologies. Further, we applied text-mining approaches to extract habitat information from the Encyclopedia of Life and automatically create experimental habitat classes within ENVO. RESULTS: Relative to its state in 2013, ENVO's content, scope, and implementation have been enhanced and much of its existing content revised for improved semantic representation. ENVO now offers representations of habitats, environmental processes, anthropogenic environments, and entities relevant to environmental health initiatives and the global Sustainable Development Agenda for 2030. Several branches of ENVO have been used to incubate and seed new ontologies in previously unrepresented domains such as food and agronomy. The current release version of the ontology, in OWL format, is available at http://purl.obolibrary.org/obo/envo.owl . CONCLUSIONS: ENVO has been shaped into an ontology which bridges multiple domains including biomedicine, natural and anthropogenic ecology, 'omics, and socioeconomic development. Through continued interactions with our users and partners, particularly those performing data archiving and sythesis, we anticipate that ENVO's growth will accelerate in 2017. As always, we invite further contributions and collaboration to advance the semantic representation of the environment, ranging from geographic features and environmental materials, across habitats and ecosystems, to everyday objects in household settings. PMID- 27664133 TI - Targeting Immune Checkpoints in Hematologic Malignancies. AB - The use of antibodies that target immune checkpoint molecules on the surface of T lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD 1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies. Unlike solid tumors, a number of considerations must be addressed to appropriately employ immune checkpoint inhibition in hematologic malignancies. For example, hematologic malignancies frequently obliterate the bone marrow and lymph nodes, which are critical immune organs that must be restored for appropriate response to immune checkpoint inhibition. On the other hand, hematologic malignancies are the quintessential immune responsive tumor type, as proven by the success of allogeneic stem cell transplantation (allo-SCT) in hematologic malignancies. Also, sharing an immune cell lineage, malignant hematologic cells often express immune checkpoint molecules that are absent in solid tumor cells, thereby offering direct targets for immune checkpoint inhibition. A number of clinical trials have demonstrated the potential for immune checkpoint inhibition in hematologic malignancies before and after allo-SCT. The ongoing clinical studies and complimentary immune correlatives are providing a growing body of knowledge regarding the role of immune checkpoint inhibition in hematologic malignancies, which will likely become part of the standard of care for hematologic malignancies. PMID- 27664131 TI - Application and comparison of different implanted ports in malignant tumor patients. AB - BACKGROUND: The current study aims to compare the application and convenience of the upper arm port with the other two methods of implanted ports in the jugular vein and the subclavian vein in patients with gastrointestinal cancers. METHODS: Currently, the standard of practice is placement of central venous access via an internal jugular vein approach. Perioperative time, postoperative complications, and postoperative comfort level in patients receiving an implanted venous port in the upper arm were retrospectively compared to those in the jugular vein and the subclavian vein from April 2013 to November 2014. RESULTS: Three hundred thirty four patients are recruited for this analysis, consisting of 107 in the upper arm vein group, 70 in the jugular vein group, and 167 in the subclavian vein group. The occurrence of catheter misplacement in the upper arm vein is higher than that in the other two groups (13.1 vs. 2.9 vs. 5.4 %, respectively, P = 0.02), while the other complications in the perioperative period were not significantly different. The occurrence of transfusion obstacle of the upper arm vein group is significantly lower than that of the jugular and subclavian groups (0.9 vs. 7.1 vs. 7.2 %, P = 0.01). The occurrence of thrombus is also lower than that of other two groups (0.9 vs. 4.3 vs. 3.6 %, P = 0.03). Regarding the postoperative comfort, the influences of appearance (0 vs. 7.1 vs. 2.9 %, P = 0.006) and sleep (0.9 vs. 4.2 vs. 10.7 %, P = 0.003) are significantly better than those of the jugular and subclavian vein groups. CONCLUSIONS: Compared to the jugular and the subclavian vein groups, the implanted venous port in the upper arm vein has fewer complications and more convenience and comfort, and might be a superior novel choice for patients requiring long-term chemotherapy or parenteral nutrition. PMID- 27664135 TI - HSV presence in brains of individuals without dementia: the TASTY brain series. AB - Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology. We investigated the prevalence of HSV type 1 and 2 in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology. HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, of which six had Alzheimer's disease neuropathological amyloid beta (Abeta) aggregations. Additionally, serological data revealed 86% of serum samples tested were IgG positive for HSV. In conclusion, we report epidemiological evidence of the presence of HSV in brain tissue free from encephalitis symptoms in a cohort most closely representing the general population (a minimum prevalence of 1.9%). Whereas 6/11 samples with HSV DNA in the brain tissue had Abeta aggregations, most of those with Abeta aggregations did not have HSV present in the brain tissue. PMID- 27664136 TI - Causal Learning in Gambling Disorder: Beyond the Illusion of Control. AB - Causal learning is the ability to progressively incorporate raw information about dependencies between events, or between one's behavior and its outcomes, into beliefs of the causal structure of the world. In spite of the fact that some cognitive biases in gambling disorder can be described as alterations of causal learning involving gambling-relevant cues, behaviors, and outcomes, general causal learning mechanisms in gamblers have not been systematically investigated. In the present study, we compared gambling disorder patients against controls in an instrumental causal learning task. Evidence of illusion of control, namely, overestimation of the relationship between one's behavior and an uncorrelated outcome, showed up only in gamblers with strong current symptoms. Interestingly, this effect was part of a more complex pattern, in which gambling disorder patients manifested a poorer ability to discriminate between null and positive contingencies. Additionally, anomalies were related to gambling severity and current gambling disorder symptoms. Gambling-related biases, as measured by a standard psychometric tool, correlated with performance in the causal learning task, but not in the expected direction. Indeed, performance of gamblers with stronger biases tended to resemble the one of controls, which could imply that anomalies of causal learning processes play a role in gambling disorder, but do not seem to underlie gambling-specific biases, at least in a simple, direct way. PMID- 27664134 TI - Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish. AB - Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS), a psychomotor retardation associated with mutations in the thyroid-hormone (TH) transporter MCT8 (monocarboxylate transporter 8). AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8-/-) zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8-/- larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8-/- larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8-/- larvae. Intriguingly, triiodothyronine (T3) treatment rescued hypomyelination in mct8-/- embryos before the maturation of the blood-brain barrier (BBB), but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8-/- larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders. PMID- 27664138 TI - Efficacy of adjunctive mitomycin C in transcanalicular diode laser dacryocystorhinostomy. AB - The objective of the study was to compare the success rate of transcanalicular laser dacryocystorhinostomy (TCL-DCR) with or without the use of adjunctive mitomycin C (MMC) in cases with primary nasolacrimal duct obstruction (NLDO). This retrospective study was comprised of 68 patients with uncomplicated primary NLDO. There were two groups in the study: the Group 1 (n = 35) patients underwent TCL-DCR surgery with MMC and the Group 2 (n = 33) patients underwent TCL-DCR surgery without MMC. All patients had bicanalicular silicone tube intubation. The main outcome measures were patent osteotomy as visualized endoscopically and patent nasolacrimal irrigation. The follow-up period was 12 months. All patients had unilateral TCL-DCR with silicone tube intubation. Six months following surgery, the silicone tubes were removed. At the final evaluation, success rates were 80 % in Group 1 and 78.8 % in Group 2. There was no statistically significant difference between the two groups (p = 0.52). No complications related to MMC usage were recorded during the study period. Intraoperative use of MMC has no beneficial effect on the success rate in TCL-DCR. PMID- 27664137 TI - The Role of Long Non-Coding RNAs in Ovarian Cancer. AB - Ovarian cancer is the most fatal tumor of female's reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified some suitable biomarkers to facilitate the early detection, the prognosis evaluation, and the assessment of treatment response. However, the aim of this review is to investigate the role of long non coding RNAs (lncRNAs) in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers. We performed an online literature search of the MEDLINE/PubMed databases using the keywords, including ovarian cancer, lncRNA, and biomarker. We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients' survival, metastasis potential, as well as treatment response. Expression profiling and methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response. PMID- 27664139 TI - Validity and reliability of the Short Form 36 Health Surveys (SF-36) among patients with spondyloarthritis in Singapore. AB - The Short Form 36 Health Survey (SF-36) is a popular health-related quality of life (HrQoL) tool. However, few studies have assessed its psychometric properties in patients with spondyloarthritis (SpA). We therefore aimed to assess the reliability and validity of the SF-36 in patients with SpA in Singapore. Cross sectional data from a registry of 196 SpA patients recruited from a dedicated tertiary referral clinic in Singapore from 2011 to 2014 was used. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments framework. Internal consistency reliability was assessed using Cronbach's alpha. Construct validity was assessed through 33 a priori hypotheses by correlations of the eight subscales and two summary scores of SF-36 with other health outcomes. Known-group construct validity was assessed by comparison of the means of the subscales and summary scores of the SF-36 of SpA patients and the general population of Singapore using student's t tests. Among 196 patients (155 males (79.0 %), median (range) age: 36 (17-70), 166 Chinese (84.6 %)), SF-36 scales showed high internal consistency ranging from 0.88 to 0.90. Convergent construct validity was supported as shown by fulfillment of all hypotheses. Divergent construct validity was supported, as SF-36 MCS was not associated with PGA, pain and HAQ. Known-group construct validity showed SpA patients had lower scores of 3.8-12.5 when compared to the general population at p < 0.001. This study supports the SF-36 as a valid and reliable measure of HrQoL for use in patients with SpA at a single time point. PMID- 27664140 TI - Fibromyalgia is associated to receiving chronic medications beyond appropriateness: a cross-sectional study. AB - The objectives of this study are to describe appropriateness and drug treatment of comorbidities in fibromyalgia (FM). Cross-sectional study of a group of patients. Number of drugs, indication, duration and appropriateness of prescriptions were evaluated. Patients were classified as: group 1, (FM/FM) previous FM diagnosis and fulfilling criteria; group 2, (noFM/noFM) other diagnosis and not fulfilling criteria; and group 3, (noFM/FM) other diagnosis but fulfilling criteria. Drugs were classified into drugs for nervous system, analgesics/NSAID and drugs for other comorbidities. Appropriateness was evaluated following clinical therapeutic guidelines. A total of 159 patients were included in the study and classified into group 1, with 59 patients; group 2, with 67 patients; and group 3, with 33 patients. Group 1 received a greater number of different drugs and for a longer period of time, there were less severe comorbidities and more unjustified treatments. No difference was found between the other two groups. Major opioids were only consumed in group 1. Also, in group 1, 45.8 % of patients were attended in psychiatry versus 15.6 % in group 3 and 3 % in group 2. The number of somatic symptoms correlated significantly with the number of drugs. Nervous system treatments were of shorter duration than other drug treatments. There was no difference in severe comorbidities. Comorbidities in FM are similar to those of other patients, but they receive more drugs and for a longer period of time. Drugs for nervous system comorbidities are introduced later, when other somatic symptoms are already treated. In patients with FM the treatments for mild comorbidities are not well justified. PMID- 27664142 TI - Applications of indocyanine green in robotic urology. AB - Indocyanine green is a fluorescent molecule with wide ranging applications in minimally invasive urological surgery. This article explores the utility of ICG assisted intraoperative fluorescence in robotic urology. PMID- 27664141 TI - Benchmarking Family Therapy for Adolescent Behavior Problems in Usual Care: Fidelity, Outcomes, and Therapist Performance Differences. AB - This study evaluated whether community therapists delivering family therapy for adolescent behavior problems in usual care achieved performance benchmarks established in controlled trials for treatment fidelity and outcomes, with particular focus on individual differences in therapist performance. The study contained N = 38 adolescents (50 % male; mean age 15 years) whose self-reported race/ethnicity was Hispanic (74 %), African American (11 %), multiracial (11 %), and other (4 %). Clients were treated by 13 therapists in one community mental health clinic that delivered family therapy as the routine standard of care. Therapists provided self-report data on adherence to core family therapy techniques; these scores were inflation-adjusted based on concordance with observer reports. Results showed that community therapists surpassed the fidelity benchmark for core family therapy techniques established by research therapists during a controlled trial. Regarding change in client functioning at 6-month follow-up, community therapists were equivalent to the benchmark for internalizing symptoms and superior for externalizing symptoms and delinquent acts. Community therapists also demonstrated a high degree of performance uniformity: Each one approximated the fidelity benchmark, and only two produced relatively weak outcomes on any of the client change indicators. Caveats for interpreting therapist performance data, given the small sample size, are described. Recommendations are made for developing therapist-report fidelity measures and utilizing statistical process control methods to diagnose therapist differences and enhance quality assurance procedures. PMID- 27664143 TI - Improved transoral surgical tool design by CT measurements of the oral cavity and pharynx. AB - The majority of head and neck cancers arise from the oral cavity and oropharynx. Many of these lesions will be amenable to surgical resection using transoral approaches including transoral robotic surgery (TORS). To develop and control TORS tools, precise dimensions of the oral cavity and pharynx are desirable. CT angiograms of 76 patients were analyzed. For the oral cavity, only the maximum length and width were measured, while for the pharynx, the width, length, and areas of the airway were all measured and the volume calculated. A prototype TORS tool was developed and tested based on the findings and dimensions. The design modification of the tool is in progress. The mean male oral cavity width and length were 93.3 +/- 4.3 and 77.0 +/- 7.2 mm, respectively, and the mean male pharyngeal width, length, area, and volume were 26.5 +/- 7.2 mm, 16.2 +/- 8.8 mm, 325 +/- 149 mm2, and 28,440 +/- 14,100 mm3, respectively, while the mean female oral cavity width and length were 84.5 +/- 12.9 and 71.0 +/- 6.3 mm, respectively, and the mean female pharyngeal width, length, area, and volume were 24.8 +/- 5.6 mm, 13.7 +/- 3.2 mm, 258 +/- 98 mm2, and 17,660 +/- 7700 mm3, respectively. The developed TORS tool was tested inside the oral cavity of an intubation mannequin. These data will also be used to develop an electronic no-go cone-shape tunnel to improve the safety of the surgical field. Reporting the oral cavity and pharyngeal dimensions is important for design of TORS tools and creating control zones for the workspace of the tool inside the oral cavity. PMID- 27664145 TI - The Primates 2016 Most-Cited Paper Award is conferred upon the following authors: M. F. Jaman and M. A. Huffman, G. Hanya et al., and M. LaFleur et al. PMID- 27664144 TI - Self-Reported Symptoms of Parkinson's Disease by Sex and Disease Duration. AB - Parkinson's disease (PD) is a neurodegenerative disease with a wide range of symptom presentations. The purpose of this research was to compare self-reported motor and non-motor symptoms of PD by sex and disease duration. This study was a cross-sectional descriptive survey in community-dwelling people with PD. A total of 141 participants (64.6% response rate; 59.6% men; Mage = 69.7 years) were included. Males reported more rigidity, speech problems, sexual dysfunction, memory problems, and socializing problems than females. The number of motor symptoms in three groups divided by increments of 5 years was significantly increased. Postural instability, freezing, off periods, dyskinesia, speech problems, and hallucinations/psychosis were significantly increased as the disease duration increased. Thorough assessment of motor and non-motor symptoms could decrease the risk of inadequate symptom management. Provision of information regarding PD symptoms at each stage may help people with PD and their caregivers in planning their future care and life. PMID- 27664148 TI - Developments and current approaches in the treatment of pterygium. AB - PURPOSE: To assess and compare the studies conducted in the literature with recurrence rates and the summary of the justified treatment approaches be presented. METHOD: Pterygium, a fibrovascular tissue that proceeds from the bulbar conjunctiva towards the cornea, is quite a commonly seen ocular surface deterioration. The treatment is performed through a surgical excision, and the frequent recurrence of this disorder, despite the developments of today, is the major problem experienced in the wake of the surgery. There are various treatment methods applied for the prevention of recurrence; yet, there is no definite view as to what treatment is the most effective one. Since the recurrent pterygium cases are more aggressive than the primary pterygium, it is of great importance to determine the treatment method in which recurrence rate is the lowest. In different studies seen in the literature, there is difficulty in comparing the results due to the fact that the follow-up periods, recurrence criteria and the doses and durations of the medications administered differ from one another. CONCLUSION: When the literature is reviewed, the bare sclera technique is not used due to the high rate of recurrence, whereas successful results can be achieved through the conjunctival autograft technique. Lower recurrence rates have been reported along with the administration of mitomycin C, 5-FU and other agents that were used as an adjuvant treatment. PMID- 27664149 TI - reply to the letter to the editor 'Possible determinants of VSL#3 probiotic failure in preventing gastrointestinal adverse events associated with dacomitinib in patients with advanced non-small-cell lung cancer enrolled in ARCHER-1042 trial' by Ceccarelli et al. PMID- 27664150 TI - Occupational exposure to metals and risk of meningioma: a multinational case control study. AB - The aim of the study was to examine associations between occupational exposure to metals and meningioma risk in the international INTEROCC study. INTEROCC is a seven-country population-based case-control study including 1906 adult meningioma cases and 5565 population controls. Incident cases were recruited between 2000 and 2004. A detailed occupational history was completed and job titles were coded into standard international occupational classifications. Estimates of mean workday exposure to individual metals and to welding fumes were assigned based on a job-exposure-matrix. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression. Although more controls than cases were ever exposed to metals (14 vs. 11 %, respectively), cases had higher median cumulative exposure levels. The ORs for ever vs. never exposure to any metal and to individual metals were mostly greater than 1.0, with the strongest association for exposure to iron (OR 1.26, 95 % CI 1.0-1.58). In women, an increased OR of 1.70 (95 % CI 1.0-2.89) was seen for ever vs never exposure to iron (OR in men 1.19, 95 % CI 0.91-1.54), with positive trends in relation with both cumulative and duration of exposure. These results remained after consideration of other occupational metal or chemical co-exposures. In conclusion, an apparent positive association between occupational exposure to iron and meningioma risk was observed, particularly among women. Considering the fact that meningioma is a hormone dependent tumor, the hypothesis that an interaction between iron and estrogen metabolism may be a potential mechanism for a carcinogenic effect of iron should be further investigated. PMID- 27664152 TI - Endovascular Treatment of Thrombosis and Embolism. AB - Deep venous thrombosis (DVT) is a common disorder with a significant mortality rate. Successful endovascular treatment of acute DVT is most likely to be achieved in patients with recently formed thrombus, (<10-14 days) with acute iliofemoral DVT. Endovascular treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation. Current practice shows strong clinical tendency for the use of PCDT with or without other endovascular methods and an individualized approach for each DVT patient. PMT has not received general acceptance because of the associated risk of PE and damage to venous valves caused by thrombectomy devices. PAT is most commonly used as an adjunctive endovascular technique like balloon maceration to fragment thrombus, balloon angioplasty, stent implantation and vena cava filter placement. Interventional endovascular therapies for DVT have the potential to provide PE protection and prevention of PTS. Patient centered individualized approach for endovascular DVT treatment is recommended to optimize the ideal clinical result.Acute stroke is the leading cause of death for people above the age of 60 and the fifth leading cause in people aged 15-59. Mortality during the first 30 days of ischemic stroke is 20 % and 30 % of survivors will remain permanently disabled. Acute stroke patients within the therapeutic window must receive IVrtPA unless there is a contraindication. In case of contraindication to IVrtPA or for patients out of the therapeutic window for thrombolytics, standart of care is the intraarterial treatment. Patients have to be transferred to a comprehensive stroke center with capacity of dedicated neurovascular imaging and interventional neuroradiology. Noncontrast head CT that is used to rule out hemorrhage is followed by imaging studies dedicated to show if there is reasonable penumbra to save. Intraarterial thrombolysis has the main advantage of extended therapy window, earlier and more efficient recanalization and less risk of hemorrhage due to lower doses of thrombolytics. Mechanical thrombectomy has several advantages over IV/IA fibrinolysis including faster recanalization and less risk of hemorrhage especially in large artery occlusions. ASA guidelines recommend choosing stent retrievers over other devices for mechanical thrombectomy. Better recanalization rates and less infarct volume after mechanical thrombectomy result in higher numbers of functionally independent patients compared with other treatments. Two landmark studies that were published recently, SWIFT PRIME and MR CLEAN, showed that IA treatment especially with the new stent retrievers lead to a significant increase in functional recovery and independence in daily life after an acute stroke.Cerebral venous and sinus thrombosis (CVST) comprises nearly 0.5-1 % of all stroke cases. CVST causes different neurological deficits depending on the sinus/cortical vein involved. CVST may cause death and dependency in 13.4 % of patients. CT/CT venography and MR/MR venography can be effectively used to diagnose and to follow up CVT cases. Anticoagulation with heparin is the most widely accepted therapy to prevent the expansion of the thrombus. Patients deteriorating despite heparinization and patients presenting with very severe neurological deficits must receive endovascular treatment. Endovascular methods include intrasinus infusion of thrombolytics or heparin, balloon angioplasty, mechanical thrombectomy or a combination of different techniques. There is a higher rate or recanalization with endovascular methods compared to other medical therapies. PMID- 27664151 TI - Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study. AB - The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions. PMID- 27664153 TI - Self-adhesive resin cements: pH-neutralization, hydrophilicity, and hygroscopic expansion stress. AB - OBJECTIVES: The objective of the study was to investigate the relationship between pH-neutralization, hydrophilicity, and free hygroscopic expansion stress of self-adhesive resin cements (SARCs) after storage in artificial saliva. MATERIALS AND METHODS: The SARCs RelyX Unicem Automix 2 (RX2, 3 M ESPE), iCEM (iCEM, Heraeus) and Maxcem Elite (MCE, Kerr) were under investigation in this study. Cylinders (height * diameter, 6 * 4mm) were prepared from each material and stored in artificial saliva (7d at 37 degrees C). Cylinder height was measured at baseline and after 7 days. After storage, the compression modulus was measured to calculate the free hygroscopic expansion stress. For pH neutralization and hydrophilicity assessment, disks (height * diameter, 1 * 1.5 mm) were prepared, covered with electrolyte, and monitored over 24 h at 37 degrees C. Hydrophilicity was assessed using the static sessile drop technique at baseline and at different time intervals up to 24 h. Data were analyzed using one way ANOVA and post hoc Student-Newman-Keuls test (S-N-K, alpha = 0.05). RESULTS: After 24 h, RX2 (pH24h 4.68) had a significantly higher (p < 0.05) pH-value than MCE (pH24h 4.2) and iCEM (pH24h 3.23). iCEM showed the significantly highest hydrophilicity (p < 0.05) after 24 h (theta24h 85.02 degrees ), while MCE resulted lower (theta24h 113.01 degrees ) in comparison with RX2 (theta24h 108.11 degrees ). The resulting hygroscopic expansion stress of iCEM (29.15 MPa) was significantly higher (p < 0.05) compared to RX2 (14.5 MPa) and MCE (21.02 MPa). CONCLUSIONS: The material with lowest pH-neutralization capacity displayed higher hydrophilicity after 24 h and higher hygroscopic expansion stress after 7 days compared to those with high pH-neutralization. CLINICAL SIGNIFICANCE: Remnant hydrophilicity due to low pH-neutralization of SARCs could lead to cement interface stress build-up and long-term failure of silicate ceramic restorations. PMID- 27664154 TI - Use of an over-the-scope clipping device for closure of a jejuno-sigmoid fistula: a case report with long-term follow-up. AB - The over-the-scope clip (OTSC) system is a new technology that enables closure of fistulae which cannot be closed with a conventional clip. A 57-year-old woman had long-term hypoalbuminemia, edema and general malaise. Peroral double-balloon endoscopy (DBE) showed a jejuno-sigmoid fistula and blind loop syndrome of the jejunum and ileum, because ingested food bypassed the ileum through the fistula. She was advised to undergo surgical closure of the fistula, but she refused the procedure. For 7 years following DBE, repeat courses of antibiotics were required to treat bacterial overgrowth due to blind loop syndrome. The fistula was successfully closed using the OTSC system from the sigmoid colon side. The patient's symptoms and quality of life improved. Two years after closure, hypoalbuminemia, edema and general malaise developed again due to dislocation of the OTSC. She then accepted surgical closure of the fistula, because she had experienced improvement after closure using the OTSC. Her quality of life improved again following surgery. OTSC application can demonstrate the improvement expected after surgical closure of a fistula, and may convince a patient of the benefits of surgical closure. PMID- 27664155 TI - Extracellular vesicles are present in mouse lymph and their level differs in atherosclerosis. AB - The lymphatic system works in close collaboration with the cardiovascular system to preserve fluid balance throughout the body and is essential for the trafficking of antigen-presenting cells and lymphocytes to lymphoid organs. Recent findings have associated lymphatic dysfunction with the pathogenesis of cardiovascular-related diseases such as atherosclerosis, inflammation and obesity. Whether lymphatic dysfunction is a cause or a consequence of these diseases, as well as how, is under intensive investigation. Extracellular vesicles (EVs) are submicron vesicles released by diverse cell types upon activation or apoptosis and are considered important biomarkers for several inflammatory diseases. Thus, it is critical to characterize the presence of EVs in various biological tissues and fluids to delineate their origins and, subsequently, their functions. In the past few years, new techniques allowing the quantitative and qualitative analysis of EVs have emerged, thus facilitating the onset of studies bridging these vesicles to the lymphatic system. Using several state-of-the-art approaches, this article reports the presence of diverse EVs inclusively derived from red blood cells and platelets in lymph of healthy animals. Our results suggest that lymph from atherosclerotic mice displays a higher concentration of EVs, bringing forward the concept that EVs contained in lymph could either be a biomarker for lymphatic dysfunction or, conversely, for inflammatory disease progression. PMID- 27664156 TI - Role of circadian gene Clock during differentiation of mouse pluripotent stem cells. AB - Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs). These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any difference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et al., 2007b). After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity. PMID- 27664158 TI - Giving feedback to medical students and trainees: rules and realities. PMID- 27664157 TI - Frequent use of colistin-based drug treatment to eliminate extended-spectrum beta lactamase-producing Escherichia coli in backyard chicken farms in Thai Binh Province, Vietnam. AB - Reports of livestock infections with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E) are increasing. Based on interviews conducted over a 6 month period, we found that veterinarians in the Vietnamese province of Thai Binh prefer to prescribe colistin-based drugs (CBD) in chicken farms. We aimed to clarify whether CBD use selects for strains of colistin-resistant ESBL-E. With the cooperation of seven local households, we detected ESBL-E in chickens' feces after treating chickens with CBD. Phylogenetic groupings and the presence of CTX M/AmpC genes were determined, and the multi-antibiotic susceptibility of isolates was analyzed. Our results showed that ESBL-E presented in seven chickens' feces from two households. Seventy-two percent of ESBL-E isolates harbored CTX-M9 and the phylogenetic group A; the colistin minimum inhibitory concentration (MIC) of all isolated ESBL-E ranged from 0.064 to 1 MUg mL-1. Moreover, ESBL-E isolates were used to experimentally select for colistin resistance, and the effect of commercial CBD on ESBL-E was investigated. The results showed that an ESBL-E strain with a colistin MIC of 4 MUg mL-1 was able to grow in media with CBD. Although CBD treatment was effective, in vitro experiments demonstrated that ESBL E can easily acquire colistin resistance. Therefore, restrictions on colistin use are necessary to prevent the emergence of colistin-resistant bacteria. PMID- 27664159 TI - L-Ribose isomerase and mannose-6-phosphate isomerase: properties and applications for L-ribose production. AB - L-Ribose is a synthetic L-form monosaccharide. It is a building block of many novel nucleotide analog anti-viral drugs. Bio-production of L-ribose relies on a two-step reaction: (i) conversion of L-arabinose to L-ribulose by the catalytic action of L-arabinose isomerase (L-AI) and (ii) conversion of L-ribulose to L ribose by the catalytic action of L-ribose isomerase (L-RI, EC 5.3.1.B3) or mannose-6-phosphate isomerase (MPI, EC 5.3.1.8, alternately named as phosphomannose isomerase). Between the two enzymes, L-RI is a rare enzyme that was discovered in 1996 by Professor Izumori's group, whereas MPI is an essential enzyme in metabolic pathways in humans and microorganisms. Recent studies have focused on their potentials for industrial production of L-ribose. This review summarizes the applications of L-RI and MPI for L-ribose production. PMID- 27664160 TI - Enzymatic liquefaction of agarose above the sol-gel transition temperature using a thermostable endo-type beta-agarase, Aga16B. AB - The main carbohydrate of red macroalgae is agarose, a heterogeneous polysaccharide composed of D-galactose and 3,6-anhydro-L-galactose. When saccharifying agarose by enzymes, the unique physical properties of agarose, namely the sol-gel transition and the near-insolubility of agarose in water, limit the accessibility of agarose to the enzymes. Due to the lower accessibility of agarose to enzymes in the gel state than to the sol state, it is important to prevent the sol-gel transition by performing the enzymatic liquefaction of agarose at a temperature higher than the sol-gel transition temperature of agarose. In this study, a thermostable endo-type beta-agarase, Aga16B, originating from Saccharophagus degradans 2-40T, was characterized and introduced in the liquefaction process. Aga16B was thermostable up to 50 degrees C and depolymerized agarose mainly into neoagarooligosaccharides with degrees of polymerization 4 and 6. Aga16B was applied to enzymatic liquefaction of agarose at 45 degrees C, which was above the sol-gel transition temperature of 1 % (w/v) agarose (~35 degrees C) when cooling agarose. This is the first systematic demonstration of enzymatic liquefaction of agarose, enabled by determining the sol-gel temperature of agarose under specific conditions and by characterizing the thermostability of an endo-type beta-agarase. PMID- 27664161 TI - Environmental risk factors for sudden infant death syndrome in Japan. AB - : While the prevalence of sudden infant death syndrome (SIDS) has decreased worldwide, this decline has plateaued recently. Strategies are needed to resume the constant decrease of SIDS in Japan. A prospective electrocardiographic screening program for infants was performed between July 2010 and March 2011. Parents of 4319 infants were asked about environmental factors related to SIDS through questionnaires at a one-month medical checkup and one year. Parental awareness of prone position, smoke exposure, and breast feeding as environmental factors were 81.4 %, 69.0 %, and 47.8 %, respectively. The prevalence of laying infants exclusively in a supine position was 96.7 %. At the one-month medical checkup, smoking prevalence was 41.7 % in fathers and 2.1 % in mothers. Maternal smoking prevalence was significantly increased at one year after (p < 0.001). Multivariate regression analysis showed that risk factors for new or continued maternal smoking habits were maternal smoking habits at one month (p < 0.001), paternal smoking habits one year later (p < 0.001), and younger maternal age (p = 0.02). CONCLUSION: Most parents already avoid laying infants in the prone position, and parental smoking is still a SIDS risk concern in Japan. Smoking cessation programs should be further implemented for parents to decrease risks of SIDS in Japan. What is Known: * The prevalence of sudden infant death syndrome (SIDS) has decreased worldwide, however, this decline has plateaued recently. What is New: * Most infants were laid sleeping in the supine position (96.7 %) and were fed breast milk or a mix of expressed milk and formula (92.7 %), and 2.1 % of mothers smoked at the one-month medical checkup. * Maternal smoking prevalence significantly increased from the one-month medical checkup to one year later, and smoking mothers were more likely to feed infants by formula rather than breast milk. * Independent risk factors for new or continued maternal smoking habits included younger maternal age, maternal smoking habits at one month, and paternal smoking habits one year later. PMID- 27664162 TI - Reply to: mitochondrial diabetes in Germany and Austria. PMID- 27664165 TI - Clarity is needed on plans for digital NHS, says think tank. PMID- 27664164 TI - Plasticity of tumor cell invasion: governance by growth factors and cytokines. AB - Tumor cell migration, the basis for metastatic dissemination, is an adaptive process which depends upon coordinated cell interaction with the environment, influencing cell-matrix and cell-cell adhesion, cytoskeletal dynamics and extracellular matrix remodeling. Growth factors and cytokines, released within the reactive tumor microenvironment and their intracellular effector signals strongly impact mechanocoupling functions in tumor cells and thereby control the mode and extent of tumor invasion, including collective and single-cell migration and their interconversions. Besides their role in controlling tumor cell growth and survival, cytokines and growth factors thus provide complex orchestration of the metastatic cascade and tumor cell adaptation to environmental challenge. We here review the mechanisms by which growth factors and cytokines control the reciprocal interactions between tumor cells and their microenvironment, and the consequences for the efficacy and plasticity of invasion programs and metastasis. PMID- 27664163 TI - Prevention of Cyclophilin D-Mediated mPTP Opening Using Cyclosporine-A Alleviates the Elevation of Necroptosis, Autophagy and Apoptosis-Related Markers Following Global Cerebral Ischemia-Reperfusion. AB - The mitochondrial permeability transition pore (mPTP) is a complex channel of the inner membrane, the opening of which leads to mitochondrial swelling and dissipation of mitochondrial membrane potential (MMP). Here, we aimed to evaluate the role of the cyclophilin D (CypD) as a prominent mediator of mPTP, on necroptosis and autophagy as well as apoptosis, beyond the global cerebral ischemia-reperfusion (I/R) injury. We showed that while cerebral I/R injury is accompanied by loss of MMP, mitochondrial swelling and programmed cell death, pretreatment with cyclosporine-A (CsA) as a potent inhibitor of CypD, led to partial but significant reduction in necroptosis markers, RIP1 and RIP3 as well as activity of glutamate-ammonia ligase (GLUL) and glutamate dehydrogenase 1 (GLUD1), downstream enzymes of RIP3. Administration of CsA also partially decreased autophagy associated proteins. Furthermore, we demonstrated that Bax/Bcl-2 ratio as well as caspase-3 activation, as the executioner of apoptosis, noticeably decreased by CsA pretreatment. Taken together, our results suggest that the CypD alongside the apoptosis regulation plays a partial role in inducing necroptosis and autophagy. PMID- 27664166 TI - Percutaneous Triple and Double Osteotomies for the Treatment of Hallux Valgus. AB - BACKGROUND: Percutaneous surgery to correct deformities of the forefoot presents the advantages of using a minimal incision, which involves less soft tissue damage and less risk of wound complications. For severe deformities, percutaneous techniques have not been proven as effective. We propose a technique for the treatment of severe hallux valgus. METHODS: In a sample of 52 feet operated on 48 patients, we performed a double percutaneous osteotomy (closure proximal osteotomy and a distal Akin) or triple when a Reverdin-Isham osteotomy was added. We measured preoperatively the American Orthopaedic Foot & Ankle Society (AOFAS) score at the 1-year and 2-year follow-up, as well as the values of hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular ankle (DMAA), and shortening and elevation of the first metatarsal. The presence of metatarsalgia was recorded before and after the surgery. RESULTS: HVA, IMA, and DMAA improved from 39.3 +/- 7.1, 17.0 +/- 2.0, and 16 +/- 8.7 to 11.2 +/- 6.2, 8.4 +/- 3.4, and 8.3 +/- 6.2, respectively. In 5 cases (10%), there was an elevation of the distal metatarsal bone, but only in 2 cases did a transfer metatarsalgia develop. There were no significant correlations between the amount of shortening and the presence of postoperative metatarsalgia. Scores on the AOFAS scale improved from 47.6 +/- 5.6 to 89.7 +/- 10.1 points. CONCLUSION: The results are comparable to those reported with other more established techniques. Transfer metatarsalgia did not correlate with lifting or shortening of the metatarsal. We indicate the percutaneous technique for IMA above 15 degrees and increased DMAA or congruent joints. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 27664167 TI - Relationship of Prolonged Operative Time and Comorbidities With Complications After Geriatric Ankle Fractures. AB - BACKGROUND: The incidence of geriatric ankle fractures has increased during the last few decades. In contrast to younger patients, increased complication rates have been observed. Thus, the goal of the present study was to identify risk factors for perioperative complications following open reduction and internal fixation of geriatric ankle fractures. METHODS: Two hundred thirty-seven patients over the age of 65 years (mean, 72.5 +/- 6.1 years) treated for ankle fractures in our institution between 2004 and 2014 were included. Complications associated with operative treatment as well as complications requiring revision surgery were analyzed. In a multivariate analysis, risk factors were determined. RESULTS: In 68 patients (28.7%), 74 complications were documented. The most common complications were impaired wound healing and operative site infections. The multivariate analysis revealed that the operative time was the only independent risk factor for the development of a complication. The operative time as well as the presence of an open fracture represented risk factors for needing revision surgery. Comorbidities did not influence the development of complications. CONCLUSION: The operative management of geriatric ankle fractures was associated with a high complication rate. In the present study, the operative time was the only modifiable factor for the development of a complication that required revision surgery. During preoperative preparation, we believe that perfusion of the affected limb should be optimized to reduce the incidence of wound complications. LEVEL OF EVIDENCE: Level III, retrospective cohort study. PMID- 27664168 TI - Performance evaluation of multiplex PCR including Aspergillus-not so simple! AB - Multiplex PCRs have been designed for including species other than Aspergillus fumigatus for the diagnosis of invasive aspergillosis, such as microarrays, liquid-phase array, and electrospray-ionization mass spectrometry (PCR/ESI MS). These methods are based on the selection of multiple primers to amplify different species with the specificity checked by hybridization to a probe or by base composition of the amplicon for the PCR/ESI MS. When testing complex samples such as respiratory specimens, some clinically relevant species can be missed. Indeed, it is impossible to design primers able to amplify all the known fungal species with the same efficiency. Therefore, the best amplified species may not be the most clinically relevant. Multiplex assays have also been proposed to detect A. fumigatus DNA and azole resistance. Since the gene responsible for azole resistance is single copy and the gene used for detection is multicopy, only the high fungal loads can be evaluated. Thus, although interesting for investigating mycobiome, the multiplex assays should be used with cautious for the diagnosis of IA or the detection of resistance. For the diagnosis of invasive aspergillosis, validated quantitative PCRs specifically targeting A. fumigatus or a limited set of species to increase sensitivity is a safer option. PMID- 27664169 TI - A fucose specific lectin from Aspergillus flavus induced interleukin-8 expression is mediated by mitogen activated protein kinase p38. AB - Aspergillus flavus is an ubiquitous, opportunistic fungus responsible to cause invasive fungal allergic diseases, including bronchopulmonary invasive aspergillosis in persons with altered immune function. Lectins have been implicated as interaction mediators between the pathogenic fungi and human host. We isolated L-fucose specific lectin from A. flavus (FFL) and purified it to homogeneity with a combination of ion exchange and hydrophobic interaction chromatography methods. Its hemagglutination activity was significantly inhibited by 125 MUM L-fucose as compared to other sugars and sugar derivatives. We, then used human cell line L-132, and U937 cell line to explore the possible cytotoxicity and proinflammatory effect of this fucose-specific lectin. The lectin induced the expression of proinflammatory cytokine interleukin-8 (IL-8) in a dose-dependent manner, and it was found to be associated with the p38 mitogen activated protein kinase (MAPK). The p38MAPK signalling pathway regulates the transcription factor activator protein-1 (AP-1) activity, which is the integration point of many signals that can differentially affect the expression and transcriptional activity of a cell. We observed activation of c-Jun, a critical component of the AP-1 complex, mediated by p38MAPK upon the FFL treatment in L-132 cells. Finally, inhibition of p38MAPK by a specific inhibitor attenuates the c-Jun, suggesting the p38MAPK involvement in the c-Jun activation, which in turn transcriptionally activates the induction of IL-8 in response to the lectin. Thus, this study showed a potential lectin-mediated mechanism to modulate the immune response during host-fungus interactions. PMID- 27664172 TI - 2016 Year in Review. PMID- 27664171 TI - Comparison Between Quality of Care Provided by Trained Feeding Assistants and Certified Nursing Assistants During Between-Meal Supplementation in Long-Term Care Settings. AB - The purpose of this study was to compare the quality of feeding assistance provided by trained non-nursing staff with care provided by certified nursing assistants (CNAs). Research staff provided an 8-hr training course that met federal and state requirements to non-nursing staff in five community long-term care facilities. Trained staff were assigned to between-meal supplement and/or snack delivery for 24 weeks. Using standardized observations, research staff measured feeding assistance care processes between meals across all study weeks. Trained staff, nurse aides, and upper level staff were interviewed at 24 weeks to assess staff perceptions of program impact. Trained staff performed significantly better than CNAs for 12 of 13 care process measures. Residents also consumed significantly more calories per snack offer from trained staff ( M = 130 +/- 126 [ SD] kcal) compared with CNAs ( M = 77 +/- 94 [ SD] kcal). The majority of staff reported a positive impact of the training program. PMID- 27664170 TI - Induction of cyclooxygenase-2 gene by Candida albicans through EGFR, ERK, and p38 pathways in human urinary epithelium. AB - In the present data, we found that Candida albicans (C. albicans) caused bladder epithelial cell morphology alteration, cell damage, and inflammatory responses, including cyclooxygenase-2 (COX-2) gene and protein expression as well as prostaglandin E2 accumulation. In addition, the molecular pathway underlying C. albicans-induced urothelial COX-2 gene expression was examined. Among MAPK pathways, phosphorylation of ERK1/2, p38, and JNK each increased following C. albicans infection for 12 h. However, C. albicans-induced COX-2 protein expression was inhibited by specific inhibitors of ERK and p38 (U0126 and SB203580) but not by JNK inhibitor SP600125. Additional evidence came from the increased amount of phosphorylated RSK that is the mutual downstream molecule of ERK1/2 and p38. Furthermore, phosphorylation of RSK protein was reduced by the ERK and p38 inhibitor, suggesting that the urothelial COX-2 gene was induced majorly though the ERK/p38-RSK pathway by C. albicans infection. We also found transcription factor CREB-1 showed increased binding to the COX-2 gene promoter by chromatin immunoprecipitation assay. Next, we used receptor inhibitors including Toll-like receptor (TLR)-Myd88 inhibitor ST2825, Dectin-Syk inhibitor Syk inhibitor, and epidermal growth factor receptor (EGFR) inhibitor PD168393 to identify which one was the main target associated with C. albicans binding. The results revealed that it was EGFR, recognized by C. albicans, that mostly mediated the ERK/p38-RSK pathway activation to induce COX-2 gene expression, but this was not the case for TLRs and Dectin receptors. In summary, these results demonstrated the EGFR-ERK/p38-RSK-CREB-1 pathway was involved significantly in the C. albicans-induced COX-2 expression in human urothelium. PMID- 27664173 TI - Prime time to resuscitate clinical medicine and kill diagnostic greed? AB - Modern healthcare faces the challenges of rising costs, increasing expectations of patients and changing disease patterns. Physicians practise medicine in an era of easy availability and access to a plethora of modern and sometimes expensive diagnostic aids. The powerful utility of clinical skills cannot be underestimated nor lost. The physician has a powerful platform to encourage the rational use of tests, prevent wasteful overutilisation and ensure that tests do not cause more harm than benefit in physical, emotional or financial terms. Diagnostic skills should not be substituted by diagnostic greed. It is possible to do more for the patient rather than to the patient. PMID- 27664174 TI - Avoiding alert fatigue in pulmonary embolism decision support: a new method to examine 'trigger rates'. AB - A clinical decision support system (CDSS) is integrated into the electronic health record (EHR) and allows physicians to easily use a clinical decision support (CDS) tool. However, often CDSSs are integrated into the EHR with poor adoption rates. One reason for this is secondary to 'trigger fatigue'. Therefore, we developed a new and innovative usability process named 'sensitivity and specificity trigger analysis' (SSTA) as part of our larger project around a pulmonary embolism decision support tool. SSTA will enable programmers to examine optimal trigger rates prior to the integration of a CDS tool into the EHR, by using a formal method of analysis. We performed a retrospective chart review. The outcome of interest was physician ordering of a CT angiography (CTA). Phrases that signify common symptoms associated with pulmonary embolism were assessed as possible triggers for the CDSS tool. We then analysed each trigger's ability to predict physician ordering of a CTA. We found that the most sensitive way to trigger the Pulmonary Embolism CDS tool while still maintaining a high specificity was by combining 1 or more pertinent symptoms with 1 or more elements of the Wells criteria. This study explored a unique methodology, SSTA, used to limit inaccurate triggering of a CDS tool prior to integration into the EHR. This methodology can be applied to other studies aiming to decrease triggering rates and increase adoption rates of previously validated CDSS tools. PMID- 27664175 TI - Determination of a single, universal threshold for caesarean section rate is not the way forward. PMID- 27664176 TI - Private sector participation in domestic waste management in informal settlements in Lagos, Nigeria. AB - Lagos is one of the fastest growing cities in Africa, which is grappling with the challenges of poorly managed urbanisation. With an estimated population of about 17.5 million, solid waste management is one of the most pressing environmental challenges currently faced in the city. It is estimated that more than 9071847.4kg of urban waste is generated every day in the city. The city lacks the capacity to deal with such magnitude of waste. Consequently, the city has involved the private sector (private sector participation) in its waste management drive. This article examines the effectiveness of this public-private sector collaboration model in waste management in informal settlements in Lagos using empirical data. Major findings of the article include the irregularity of waste collection owing to a poor road network, an inadequate transport infrastructure and the desire to maximise profit, as well as poor waste handling and disposal methods by the private sector participation operators who are not chosen based on competence and capacity to perform. Another major finding is the lack of cooperation from residents evidenced in non-payment of bills and poor packaging of wastes, resulting in wastes being littered. The article concludes on the need to restructure the scheme through proper sensitisation of residents, selection of operators with demonstrable delivery capacity and provision of a well-maintained road network to facilitate access of operators to settlements. PMID- 27664177 TI - Novel method of vulnerability assessment of simple landfills area using the multimedia, multipathway and multireceptor risk assessment (3MRA) model, China. AB - Vulnerability assessment of simple landfills was conducted using the multimedia, multipathway and multireceptor risk assessment (3MRA) model for the first time in China. The minimum safe threshold of six contaminants (benzene, arsenic (As), cadmium (Cd), hexavalent chromium [Cr(VI)], divalent mercury [Hg(II)] and divalent nickel [Ni(II)]) in landfill and waste pile models were calculated by the 3MRA model. Furthermore, the vulnerability indexes of the six contaminants were predicted based on the model calculation. The results showed that the order of health risk vulnerability index was As > Hg(II) > Cr(VI) > benzene > Cd > Ni(II) in the landfill model, whereas the ecology risk vulnerability index was in the order of As > Hg(II) > Cr(VI) > Cd > benzene > Ni(II). In the waste pile model, the order of health risk vulnerability index was benzene > Hg(II) > Cr(VI) > As > Cd and Ni(II), whereas the ecology risk vulnerability index was in the order of Hg(II) > Cd > Cr(VI) > As > benzene > Ni(II). These results indicated that As, Hg(II) and Cr(VI) were the high risk contaminants for the case of a simple landfill in China; the concentration of these in soil and groundwater around the simple landfill should be strictly monitored, and proper mediation is also recommended for simple landfills with a high concentration of contaminants. PMID- 27664178 TI - Loss of a Trans-Splicing nad1 Intron from Geraniaceae and Transfer of the Maturase Gene matR to the Nucleus in Pelargonium. AB - The mitochondrial nad1 gene of seed plants has a complex structure, including four introns in cis or trans configurations and a maturase gene (matR) hosted within the final intron. In the geranium family (Geraniaceae), however, sequencing of representative species revealed that three of the four introns, including one in a trans configuration and another that hosts matR, were lost from the nad1 gene in their common ancestor. Despite the loss of the host intron, matR has been retained as a freestanding gene in most genera of the family, indicating that this maturase has additional functions beyond the splicing of its host intron. In the common ancestor of Pelargonium, matR was transferred to the nuclear genome, where it was split into two unlinked genes that encode either its reverse transcriptase or maturase domain. Both nuclear genes are transcribed and contain predicted mitochondrial targeting signals, suggesting that they express functional proteins that are imported into mitochondria. The nuclear localization and split domain structure of matR in the Pelargonium nuclear genome offers a unique opportunity to assess the function of these two domains using transgenic approaches. PMID- 27664179 TI - Draft Genome Sequence of an Aflatoxigenic Aspergillus Species, A. bombycis. AB - Aspergillus bombycis was first isolated from silkworm frass in Japan. It has been reportedly misidentified as A. nomius due to their macro-morphological and chemotype similarities. We sequenced the genome of the A. bombycis Type strain and found it to be comparable in size (37 Mb), as well as in numbers of predicted genes (12,266), to other sequenced Aspergilli. The aflatoxin gene cluster in this strain is similar in size and the genes are oriented the same as other B- + G aflatoxin producing species, and this strain contains a complete but nonfunctional gene cluster for the production of cyclopiazonic acid. Our findings also showed that the A. bombycis Type strain contains a single MAT1-2 gene indicating that this species is likely heterothallic (self-infertile). This draft genome will contribute to our understanding of the genes and pathways necessary for aflatoxin synthesis as well as the evolutionary relationships of aflatoxigenic fungi. PMID- 27664180 TI - Transcriptional Interference Promotes Rapid Expression Divergence of Drosophila Nested Genes. AB - Nested genes are the most common form of protein-coding overlap in eukaryotic genomes. Previous studies have shown that nested genes accumulate rapidly over evolutionary time, typically via the insertion of short young duplicate genes into long introns. However, the evolutionary relationship between nested genes remains unclear. Here, I compare RNA-seq expression profiles of nested, proximal intra-chromosomal, intermediate intra-chromosomal, distant intra-chromosomal, and inter-chromosomal gene pairs in two Drosophila species. I find that expression profiles of nested genes are more divergent than those of any other class of genes, supporting the hypothesis that concurrent expression of nested genes is deleterious due to transcriptional interference. Further analysis reveals that expression profiles of derived nested genes are more divergent than those of their ancestral un-nested orthologs, which are more divergent than those of un nested genes with similar genomic features. Thus, gene expression divergence between nested genes is likely caused by selection against nesting of genes with insufficiently divergent expression profiles, as well as by continued expression divergence after nesting. Moreover, expression divergence and sequence evolutionary rates are elevated in young nested genes and reduced in old nested genes, indicating that a burst of rapid evolution occurs after nesting. Together, these findings suggest that similarity between expression profiles of nested genes is deleterious due to transcriptional interference, and that natural selection addresses this problem both by eradicating highly deleterious nestings and by enabling rapid expression divergence of surviving nested genes, thereby quickly limiting or abolishing transcriptional interference. PMID- 27664181 TI - Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population. AB - Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and -358 (rs3219175) located in the human resistin gene (RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP -358 G>A, followed by rs1423096 C>T, SNP -420 C>G, and rs10401670 C>T (P = 5.39*10-47, 1.81*10-22, 2.09*10-16, and 9.25*10-15, respectively). Meta analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3'-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP 420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population. PMID- 27664182 TI - Effects of dietary forage and calf starter on ruminal pH and transcriptomic adaptation of the rumen epithelium in Holstein calves during the weaning transition. AB - We investigated the relationship between ruminal pH and transcriptomic adaptation of the rumen epithelium (RE) of calves fed calf starter with and without forage during the weaning transition. Holstein calves were assigned to groups fed calf starter either with forage (HAY group, n = 3) or without forage (CON group, n = 4). Ruminal pH was measured continuously, and rumen fluid and epithelium were collected 3 wk after weaning. mRNA expression profiles of the RE were examined by one-color microarray. Differentially expressed genes (DEGs) were investigated using the Ingenuity Pathway Analysis (IPA). Mean and maximum ruminal pH were significantly (P < 0.05) higher, and the duration of pH < 5.8 during 1 day was significantly (P < 0.05) shorter, in the HAY group. The proportion of ruminal acetate and the acetate-to-propionate ratio were significantly (P < 0.05) lower in the CON group. DEGs encoding transcription regulators (SREBP1), insulin-like growth factor binding proteins (IGFBP7 and CTGF), ketogenic enzymes (HMGCL, BDH1, and BDH2), and a transporter (SLC16A3) were identified (P < 0.05) between the two groups. A growth factor (TGFB1) and signaling pathway (EGF and EGFR) were activated as upstream regulators. These results suggest that dietary forage alleviates ruminal acidosis, and the decrease in ruminal pH may damage the RE, leading to changes in gene expression to repair the damage. Furthermore, rumen development may be regulated by growth factor (TGFB1) and signaling pathways (EGF and IGFBP) for adaptation to feeding on calf starter with and without forage during the weaning transition. PMID- 27664184 TI - States, Nations, Health Policy, and Nursing. PMID- 27664185 TI - Burns from e-cigarettes and other electronic nicotine delivery systems. PMID- 27664183 TI - Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. AB - Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via host G protein-coupled receptor (GPCRs). We previously showed that an acute SCFA bolus decreases blood pressure (BP) in anesthetized mice, an effect mediated primarily via Gpr41. In this study, our aims were to identify the cellular localization of Gpr41 and to determine its role in BP regulation. We localized Gpr41 to the vascular endothelium using RT-PCR: Gpr41 is detected in intact vessels (with endothelium) but is absent from denuded vessels (without endothelium). Furthermore, using pressure myography we confirmed that SCFAs dilate resistance vessels in an endothelium-dependent manner. Since we previously found that Gpr41 mediates a hypotensive response to acute SCFA administration, we hypothesized that Gpr41 knockout (KO) mice would be hypertensive. Here, we report that Gpr41 KO mice have isolated systolic hypertension compared with wild-type (WT) mice; diastolic BP was not different between WT and KO. Older Gpr41 KO mice also exhibited elevated pulse wave velocity, consistent with a phenotype of systolic hypertension; however, there was no increase in ex vivo aorta stiffness (measured by mechanical tensile testing). Plasma renin concentrations were also similar in KO and WT mice. The systolic hypertension in Gpr41 KO is not salt sensitive, as it is not significantly altered on either a high- or low-salt diet. In sum, these studies suggest that endothelial Gpr41 lowers baseline BP, likely by decreasing active vascular tone without altering passive characteristics of the blood vessels, and that Gpr41 KO mice have hypertension of a vascular origin. PMID- 27664186 TI - Restriction of FODMAP in the management of bloating in irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a common functional bowel disorder. Up to 96% of IBS patients experience bloating, resulting in poor response to conventional therapies and high consultation rates. Many IBS patients report that food triggers symptoms, particularly diets with poorly absorbed, short-chain carbohydrates, and restrict intake of certain foods to control their symptoms. IBS patients are especially susceptible to an attack due to visceral hypersensitivity. An emerging therapeutic strategy excludes fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) from the diet. There is evidence supporting the efficacy of a low FODMAP diet in improving symptoms of bloating in IBS patients. Individualised, structured dietary guidance may benefit those with persistent troublesome symptoms despite traditional therapies. In view of the multifactorial aetiology of the condition, it is probably best to use a multipronged approach, involving combination therapies, to address bloating in IBS patients. PMID- 27664187 TI - Tamoxifen citrate-loaded poly(d,l) lactic acid nanoparticles: Evaluation for their anticancer activity in vitro and in vivo. AB - The optimization of tamoxifen citrate entrapment and its release from biodegradable poly(d,l) lactic acid nanoparticles are prepared by modified spontaneous emulsification solvent diffusion method. Since the addition of tamoxifen citrate induces the formation of drug crystals from nanoparticle suspension the influence of several parameters on tamoxifen citrate encapsulation was investigated. In vitro studies for cytotoxicity, DNA ladder, and the expression of Bcl-2-Bax expression were also investigated for MCF-7 and MDA-MB 231 cells after the addition of tamoxifen citrate alone and tamoxifen citrate poly(d,l) lactic acid-nanoparticles (encapsulated tamoxifen citrate). From results, it was noticed that the size and zeta potential of the drug loaded nanoparticles were not differed much in their physicochemical properties from drug free counterparts. The drug-loaded and drug-free nanoparticles exhibited size of in between 271.4 and 282.7 nm and zeta potential of -34 to -27.4 mV, respectively. There was significant increase in drug incorporation in the particles noticed in dichloromethane + methanol system in comparison to acetone + methanol and ethyl acetate + methanol systems. The drug was partly released from the nanoparticles after 48 h of incubation at 37C. From Fourier transform infrared spectroscopy and differential scanning calorimetry data demonstrated drug-polymer characteristics within the nanoparticles and unincorporated drug that appeared in the form of crystals from polarized microscopic study. MCF-7 and MDA-MB-231 cells were more sensitive to tamoxifen citrate-poly(d,l) lactic acid nanoparticles than tamoxifen citrate alone. DNA ladder and the expression of Bax to Bcl-2 ratio were much higher in tamoxifen citrate encapsulated in nanoparticles than that in tamoxifen citrate alone. These results demonstrated the feasibility of encapsulation of tamoxifen citrate and its enhanced efficiency in vitro and in vivo studies. PMID- 27664188 TI - Phylogenomics of Lophotrochozoa with Consideration of Systematic Error. AB - Phylogenomic studies have improved understanding of deep metazoan phylogeny and show promise for resolving incongruences among analyses based on limited numbers of loci. One region of the animal tree that has been especially difficult to resolve, even with phylogenomic approaches, is relationships within Lophotrochozoa (the animal clade that includes molluscs, annelids, and flatworms among others). Lack of resolution in phylogenomic analyses could be due to insufficient phylogenetic signal, limitations in taxon and/or gene sampling, or systematic error. Here, we investigated why lophotrochozoan phylogeny has been such a difficult question to answer by identifying and reducing sources of systematic error. We supplemented existing data with 32 new transcriptomes spanning the diversity of Lophotrochozoa and constructed a new set of Lophotrochozoa-specific core orthologs. Of these, 638 orthologous groups (OGs) passed strict screening for paralogy using a tree-based approach. In order to reduce possible sources of systematic error, we calculated branch-length heterogeneity, evolutionary rate, percent missing data, compositional bias, and saturation for each OG and analyzed increasingly stricter subsets of only the most stringent (best) OGs for these five variables. Principal component analysis of the values for each factor examined for each OG revealed that compositional heterogeneity and average patristic distance contributed most to the variance observed along the first principal component while branch-length heterogeneity and, to a lesser extent, saturation contributed most to the variance observed along the second. Missing data did not strongly contribute to either. Additional sensitivity analyses examined effects of removing taxa with heterogeneous branch lengths, large amounts of missing data, and compositional heterogeneity. Although our analyses do not unambiguously resolve lophotrochozoan phylogeny, we advance the field by reducing the list of viable hypotheses. Moreover, our systematic approach for dissection of phylogenomic data can be applied to explore sources of incongruence and poor support in any phylogenomic data set. [Annelida; Brachiopoda; Bryozoa; Entoprocta; Mollusca; Nemertea; Phoronida; Platyzoa; Polyzoa; Spiralia; Trochozoa.]. PMID- 27664189 TI - Exercise training increases protein O-GlcNAcylation in rat skeletal muscle. AB - Protein O-GlcNAcylation has emerged as an important intracellular signaling system with both physiological and pathophysiological functions, but the role of protein O-GlcNAcylation in skeletal muscle remains elusive. In this study, we tested the hypothesis that protein O-GlcNAcylation is a dynamic signaling system in skeletal muscle in exercise and disease. Immunoblotting showed different protein O-GlcNAcylation pattern in the prototypical slow twitch soleus muscle compared to fast twitch EDL from rats, with greater O-GlcNAcylation level in soleus associated with higher expression of the modulating enzymes O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and glutamine fructose-6-phosphate amidotransferase isoforms 1 and 2 (GFAT1, GFAT2). Six weeks of exercise training by treadmill running, but not an acute exercise bout, increased protein O GlcNAcylation in rat soleus and EDL There was a striking increase in O GlcNAcylation of cytoplasmic proteins ~50 kDa in size that judged from mass spectrometry analysis could represent O-GlcNAcylation of one or more key metabolic enzymes. This suggests that cytoplasmic O-GlcNAc signaling is part of the training response. In contrast to exercise training, postinfarction heart failure (HF) in rats and humans did not affect skeletal muscle O-GlcNAcylation level, indicating that aberrant O-GlcNAcylation cannot explain the skeletal muscle dysfunction in HF Human skeletal muscle displayed extensive protein O GlcNAcylation that by large mirrored the fiber-type-related O-GlcNAcylation pattern in rats, suggesting O-GlcNAcylation as an important signaling system also in human skeletal muscle. PMID- 27664190 TI - Sex differences in adult rat insulin and glucose responses to arginine: programming effects of neonatal separation, hypoxia, and hypothermia. AB - Acute neonatal hypoxia, a common stressor, causes a spontaneous decrease in body temperature which may be protective. There is consensus that hypothermia should be prevented during acute hypoxia in the human neonate; however, this may be an additional stress with negative consequences. We hypothesize that maintaining body temperature during hypoxia in the first week of postnatal life alters the subsequent insulin, glucose, and glucagon secretion in adult rats. Rat pups were separated from their dam daily from postnatal days (PD) 2-6 for the following 90 min experimental treatments: (1) normoxic separation (control), (2) hypoxia (8% O2) allowing spontaneous hypothermia, (3) normoxic hypothermia with external cold, and (4) exposure to 8% O2 while maintaining body temperature using external heat. An additional normoxic non-separated control group was performed to determine if separation per se changed the adult phenotype. Plasma insulin, glucose, and glucagon responses to arginine stimulation were evaluated from PD105 to PD133. Maternal separation (compared to non-separated neonates) had more pronounced effects on the adult response to arginine compared to the hypoxic, hypothermic, and hypoxic-isothermic neonatal treatments. Adult males exposed to neonatal maternal separation had augmented insulin and glucose responses to arginine compared to unseparated controls. Additionally, neonatal treatment had a significant effect on body weight gain; adults exposed to neonatal maternal separation were significantly heavier. Female adults had significantly smaller insulin and glucose responses to arginine regardless of neonatal treatment. Neonatal maternal separation during the first week of life significantly altered adult beta-cell function in a sexually dimorphic manner. PMID- 27664191 TI - The Social Feedback Hypothesis and Communicative Development in Autism Spectrum Disorder: A Response to Akhtar, Jaswal, Dinishak, and Stephan (2016). PMID- 27664192 TI - On Social Feedback Loops and Cascading Effects in Autism: A Commentary on Warlaumont, Richards, Gilkerson, and Oller (2014). PMID- 27664193 TI - Pediatric Central Neurocytoma. AB - Central neurocytomas are well-differentiated tumors of neuronal origin. These are relatively uncommon in the pediatric population. Anaplastic features reflected by brisk mitotic activity, microvascular proliferation, necrosis, and MIB-1 labeling index >2% or 3% have been proposed to indicate aggressive behavior. Because of its rarity, there is paucity of data regarding the histologic spectrum and outcome of central neurocytomas in children. With this short series, we describe our observations of the clinicopathologic characteristics and outcome of this tumor in children over a 5-year period. PMID- 27664194 TI - Cognitive Function and Heat Shock Protein 70 in Children With Temporal Lobe Epilepsy. AB - We conducted the present study to examine cognitive function and serum heat shock protein 70 levels among children with temporal lobe epilepsy. The Stanford-Binet Intelligence Test was carried out to examine cognitive function in 30 children with temporal lobe epilepsy and 30 controls. Serum heat shock protein 70 levels were determined with an enzyme-linked immunosorbent assay. The epilepsy group had significantly lower cognitive function testing scores and significantly higher serum heat shock protein 70 levels than the control group; there were significant negative correlations between serum heat shock protein 70 levels and short-term memory and composite scores. Children with uncontrolled seizures had significantly lower verbal reasoning scores and significantly higher serum heat shock protein 70 levels than children with controlled seizures. Children with temporal lobe epilepsy have cognitive dysfunction and elevated levels of serum heat shock protein 70, which may be considered a stress biomarker. PMID- 27664195 TI - Neurocognitive Profiles in Childhood Absence Epilepsy. AB - Although neuropsychological studies have demonstrated specific cognitive impairments in children with childhood absence epilepsy (CAE), the potential role of the frontal lobe in these cognitive deficits remains unclear. We therefore evaluated cognitive functions related to and unrelated to the functionality of the frontal lobe in childhood absence epilepsy patients and control subjects. Thirty-seven childhood absence epilepsy patients and 37 age- and gender-matched healthy control subjects were recruited and assessed using a computerized neuropsychological test battery. Childhood absence epilepsy patients, especially a drug-naive subgroup, showed cognitive deficits in reasoning, visual attention, and executive function, which are typical cognitive functions of the frontal lobe. In contrast, treated childhood absence epilepsy patients only exhibited cognitive deficits in visual attention. There were no significant between-group differences for other cognitive tests. Our findings suggest that frontal lobe related cognitive deficits represent the characteristic neuropsychological profile associated with childhood absence epilepsy. PMID- 27664196 TI - In ovo validation model to assess the efficacy of commercial prebiotics on broiler performance and oxidative stability of meat. AB - The purpose of this study was to examine the effect of in ovo injection of 2 different prebiotics, DiNovo (DN; Laminaria spp., extract containing laminarin and fucoidan) and Bi2tos (BI; non-digestive trans-galactooligosaccharides from milk lactose digested with Bifidobacterium bifidum NCIMB 41171), on growth, slaughter traits, intramuscular fat percentage (IF) and muscle fiber diameter, and lipid oxidation of meat in chickens reared under commercial conditions, following an in ovo trial protocol. On d 12 of embryonic incubation, 350,560 Ross 308 eggs were randomly divided into 3 experimental groups and automatically injected in ovo with: physiological saline (control group), BI at dose of 3.5 mg/embryo and DN at dose of 0.88 mg/embryo. Hatched chicks (males and females) were allocated dependent on treatment group into 3 poultry houses on each farm (3 farms in total) with a stocking density of 21.2 to 21.5 chicks/m2 At 42 d of age, 14 randomly chosen birds (7 males and 7 females), per each treatment from each farm, were individually weighed and slaughtered. The results showed no significant differences of final number of chickens/chicken house, mortality, BW per treatment, stocking density (kg/m2), feed intake, feed conversion rate (FCR), and European Broiler Index among 3 experimental groups. Treatments with BI and DN were associated with slight increases (P > 0.05) in average BW and a minor improvement (P > 0.05) of FCR in BI group. Slaughtered chickens from DN and BI treated groups had significantly increase of BW, carcass weight, carcass yield, and breast muscle weight compared with the control group. IF and muscle fiber diameter were similar among groups. Males had significantly higher slaughter traits compared to females, except for breast muscle yield. The prebiotic treatments led to a higher lipid oxidation in meat, even if the detected TBA reactive substances were below the critical value recognized for meat acceptability. In conclusion, in ovo administration of prebiotics was associated with improvements in a number of parameters of relevance to commercial poultry production. PMID- 27664197 TI - Effect of zinc imprinting and replacing inorganic zinc with organic zinc on early performance of broiler chicks. AB - The goal of this study was to determine the effects of feeding a zinc (Zn) deficient diet to broiler chicks for 96 h post-hatch followed by feeding diets with different Zn sources and supplemental levels (5 to 21 d) on the growth performance, tissue, and excreta Zn content. At the start of the study, four hundred 20-day-old male broiler chicks were divided into two groups. One group was fed a corn soybean meal based diet containing 25 mg of Zn/kg (imprinting diet, ID). The second group was fed the basal diet supplemented with 40 mg of Zn/kg from Zn oxide (ZnO) (non-imprinting diet, NID). Both groups were fed these diets for 96 h. At d 5, chicks from each group were randomly assigned to the dietary treatments consisting of the basal diet alone or the basal diet supplemented with 8 or 40 mg/kg Zn as ZnO or Zn proteinate. Main effects of post hatch Zn ID were observed on feed intake and G:F. ID decreased (P < 0.05) feed intake and improved (P < 0.05) the gain to feed ratio (G:F) of 14 and 21 d old chicks compared to G:F of chicks fed NID. Additionally, G:F for 14 and 21 d was improved (P < 0.05) by interaction of Zn source * level. Furthermore, at d 21 chicks fed the ID had a lower (P < 0.05) Zn content in the tibia ash and excreta, and a higher (P < 0.05) Zn content in the pancreas tissue compared to chicks fed NID. These results suggest that Zn imprinting can affect body Zn stores and early performance. PMID- 27664199 TI - Effect of different amylases on the utilization of cornstarch in broiler chickens. AB - This study compared the effect of different amylases on the utilization of cornstarch in broiler chickens fed a corn-based diet. Three-day-old Arbor Acres plus male chickens were randomly divided into 7 treatments and fed a diet supplemented with different sources and concentrations of amylase: 1,500 U/kg and 3,000 U/kg alpha-1,4 amylase from Aspergillus oryzae (alpha-amylase A); 480 U/kg and 960 U/kg alpha-1,4 amylase from Bacillus subtilis (alpha-amylase B); 200 U/kg and 400 U/kg alpha-1,6 isoamylase from B. subtilis; and the control. The experimental period comprised 11 d, during which performance, nutrient digestibility, digestive enzyme activity, intestinal morphology, and glucose transporter transcription of the chickens were evaluated. The results indicated that 1,500 U/kg alpha-amylase improved the digestibility of energy and decreased the feed conversion rate compared to alpha-1,6 isoamylase (P < 0.05). Supplemental 400 U/kg alpha-1,6 isoamylase decreased ileal digestibility of amylopectin and total starch (P < 0.05) compared to 200 U/kg alpha-1,6 isoamylase, alpha-amylase A, alpha-amylase B, and the control (P < 0.05). Supplemental alpha-1,6 isoamylase decreased (P < 0.05) insulin content. Supplemental 3,000 U/kg alpha-amylase A and alpha-1,6 isoamylase increased (P < 0.05) the relative weight of the liver. In addition, 3,000 U/kg alpha-amylase A, 480 U/kg alpha-amylase B, and alpha-1,6 isoamylase decreased the V:C in the duodenum and ileum. alpha-amylase A increased sucrase activity in the jejunum (P < 0.05), whereas 400 U/kg alpha-1,6 isoamylase reduced maltase activity in the duodenum (P < 0.05). Furthermore, 3,000 U/kg alpha-amylase A and alpha-amylase B decreased (P < 0.05) sodium/glucose cotransporter 1 (SGLT1) mRNA expression in the duodenum and jejunum. However, 200 U/kg alpha-1,6 isoamylase increased glucose transporter 2 (GLUCT2) in the duodenum (P < 0.05). These results suggest that exogenous amylase affects the digestibility of starch by affecting disaccharidase activity in the intestine, nutrient requirements for intestinal maintenance by the V:C, and nutrient absorption and metabolism via GLU transporter mRNA expression. Different sources and concentrations of amylases had varying effects on broilers. PMID- 27664198 TI - Effect of supplemental fermented Ginkgo biloba leaves at different levels on growth performance, meat quality, and antioxidant status of breast and thigh muscles in broiler chickens. AB - The present study was conducted to investigate the influence of dietary supplementation with different levels of fermented Ginkgo biloba leaves (FGBL) on growth performance, slaughter performance, meat quality, antioxidant enzyme capacity, and free radical scavenging activities of muscles in broiler chickens. A total of 648 one-d-old broiler chickens were randomly allocated into six dietary treatments, including control group (CON group: basal diet), FGBL1, FGBL2, FGBL3, FGBL4, and FGBL5 groups (basal diet containing 1.5, 2.5, 3.5, 4.5, and 5.5 g/kg FGBL, respectively). Body weight gain and feed intake were recorded at 1, 21, and 42 d. At 42 d, 2 birds from each replicate were slaughtered. The results indicated that 3.5 g/kg FGBL diet significantly increased (P < 0.05) ADFI and ADG in 1 to 42 d and ADFI in 22 to 42 d compared with the CON group. In 1 to 21 d, 4.5 g/kg FGBL diet improved (P < 0.05) ADFI and ADG. With dietary FGBL increasing, the feed: gain ratio (F/G) in 1 to 21 d was significantly decreased (P < 0.05). However, birds fed with 5.5 g/kg FGBL had a higher (P < 0.05) F/G compared with other groups in 22 to 42 d and 1 to 42 d. In addition, FGBL3 and FGBL4 showed lower (P < 0.05) L* value in breast muscle, cooking loss in thigh muscle and lower 24 h and 48 h drip loss in both breast and thigh muscles than those of other groups. Furthermore, birds in the FGBL3 and FGBL4 groups increased (P < 0.05) the activity of total superoxide dismutase and total antioxidant capability in muscles, and the scavenging activities of 2,2?-azino-bis (3 ethylbenzothiazoline-6-sulfonic) acid radical, OH*, and O2*- in thigh muscle, decreased (P < 0.05) malondialdehyde concentration in thigh muscle, as compared to the CON group. In conclusion, FGBL had the potential to improve the growth performance, meat quality and antioxidant status of broiler chickens. The optimal dose in the present study of FGBL in broiler diets was from 3.5 to 4.5 g/kg. PMID- 27664201 TI - Characterisation and quantification of changes in odorants from litter headspace of meat chickens fed diets varying in protein levels and additives. AB - The effect of dietary crude protein (CP) and additives on odor flux from meat chicken litter was investigated using 180 day-old Ross 308 male chicks randomly allocated to five dietary treatments with three replicates of 12 birds each. A 5 * 3 factorial arrangement of treatments was employed. Factors were: diet (low CP, high CP, high CP+antibiotic, high CP+probiotic, high CP+saponin) and age (15, 29, 35 days). The antibiotic used was Zn bacitracin, the probiotic was a blend of three Bacillus subtilis strains and the saponin came from a blend of Yucca and Quillaja. Odorants were collected from litter headspace with a flux hood and measured using selective ion flow tube mass spectrometry (SIFT-MS). Litter moisture, water activity (Aw), and litter headspace odorant concentrations were correlated. The results showed that low CP group produced lower flux of dimethyl amine, trimethyl amine, H2S, NH3, and phenol in litter compared to high CP group (P < 0.05). Similarly, high CP+probiotic group produced lower flux of H2S (P < 0.05) and high CP+saponin group produced lower flux of trimethylamine and phenol in litter compared to high CP group (P < 0.05). The dietary treatments tended (P = 0.065) to have higher flux of methanethiol in high CP group compared to others. There was a diet * age interaction for litter flux of diacetyl, 3-hydroxy-2 butanone (acetoin), 3-methyl-1-butanol, 3-methylbutanal, ethanethiol, propionic acid, and hexane (P < 0.05). Concentrations of diacetyl, acetoin, propionic acid, and hexane in litter were higher from low CP group compared to all other treatments on d 35 (P < 0.05) but not on d 15 and 29. A high litter moisture increased water activity (P < 0.01) and favored the emissions of methyl mercaptan, hydrogen sulfide, dimethyl sulfide, ammonia, trimethyl amine, phenol, indole, and 3-methylindole over others. Thus, the low CP diet, Bacillus subtilis based probiotic and the blend of Yucca/Quillaja saponin were effective in reducing the emissions of some key odorants from meat chicken litter. PMID- 27664200 TI - Leucine and valine supplementation of low-protein diets for broiler chickens from 21 to 42 days of age. AB - The objective of this study was to determine the requirements and interactions between the standardized ileal digestible (SID) Leu and Val levels in low-protein diets, and their effects on performance, serum characteristics, carcass yield and diameter of muscle fibers of broiler chickens from d 21 to 42 posthatch. A total of 1,500 21-day-old Cobb 500 male broiler chickens were distributed in a completely randomized design in a 5 * 5 factorial arrangement for a total of 25 treatments with 3 replicates of 20 birds each. Treatments consisted of 5 SID Leu levels (1.0, 1.2, 1.4, 1.6, or 1.8%) and 5 SID Val levels (0.52, 0.67, 0.82, 0.97, or 1.12%). At 42 d of age, there was interaction (P < 0.05) between the SID levels of Leu and Val on feed intake and weight gain. There was a quadratic effect (P < 0.05) of Leu and Val levels on feed conversion, with minimal point estimated at the levels of 1.19 and 0.86%, respectively. Dietary Leu supplementation reduced linearly (P < 0.05) serum concentrations of triglycerides and beta-hydroxybutyrate. Dietary Leu increased (P <= 0.05) the fiber diameters of the pectoralis major muscle and breast yield at the levels of 1.24 and 1.13%, respectively, while the thigh yield was improved with the level of 0.71% Val. Abdominal fat decreased linearly (P < 0.05) with increasing levels of dietary Leu and Val. The SID Leu and Val levels needed to optimize weight gain and feed conversion in low-CP diets for broiler chickens from d 21 to 42 posthatch were estimated at 1.15 and 0.86%, and 1.19 and 0.86%, respectively. The supplementation of Leu and Val can reduce the abdominal fat deposition in birds fed low-CP diets during the grower phase. Leu and Val interactions can influence the performance but not the serum characteristics, carcass yield and diameter of muscle fibers of broilers fed low-protein diets. Therefore, it is necessary to consider the dietary Leu content to estimate the ideal level of Val in low-CP diets for optimum broiler performance. PMID- 27664202 TI - Constitutive heterochromatin in chromosomes of duck hybrids and goose hybrids. AB - Constitutive heterochromatin is a highly condensed fraction of chromatin in chromosomes. It is characterized by a high degree of polymorphism. Heterochromatin is located in the centromeric, telomeric, and interstitial parts of chromosomes. We used the CBG ( C: banding using B: arium hydroxide by G: iemsa) staining technique to identify heterochromatin in chromosomes. Analysis of karyotypes of F1 hybrids resulting from intergeneric hybridization of ducks (A. platyrhynchos * C. moschata) and interspecific crosses of geese (A. anser * A. cygnoides) were used to compare the karyotypes of 2 species of duck and 2 species of geese, as well as to compare the hybrids with the parent species. The localization of C-bands and their size were determined. In the duck hybrid, greater amounts of heterochromatin were noted in the homologous chromosomes from the duck A. platyrhynchos than in the chromosomes from the duck C. moschata. In the goose hybrid more heterochromatin was observed in the homologous chromosomes from the goose A. cygnoides than in the chromosomes from the goose A. anser. Comparison of chromosomes from the duck hybrid with chromosomes of the ducks A. platyrhynchos and C. moschata revealed nearly twice as much constitutive heterochromatin in the chromosomes of the hybrid. When chromosomes from the goose hybrid were compared with those of the geese A. anser and A. cygnoides, differences in the average content of heterochromatin were observed on only a few chromosomes. PMID- 27664203 TI - Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair. AB - The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived). PMID- 27664204 TI - The definition of IVM is clear-variations need defining. AB - Oocyte in vitro maturation (IVM) is currently defined as the maturation in vitro of immature cumulus-oocyte complexes collected from antral follicles. This is the original definition as first described by Pincus and Enzmann and then by Edwards many decades ago, and this clear and unambiguous definition has served us well ever since. In an attempt to clarify apparent differences among clinicians, the following revised definition of IVM was recently proposed: 'The retrieval of oocytes from small and intermediate sized follicles in an ovary before the largest follicle has surpassed 13 mm in mean diameter'. As such, this proposed definition should encompass the use of hCG triggering. To change the clear and long-serving definition of IVM to fit varying clinical practices requires a compelling justification based on solid scientific and clinical grounds. We are of the opinion that the proposed revised definition of IVM is counterintuitive as it includes protocols that are intended to mature oocytes in vivo The proposed definitions are cumbersome and indeed further complicate the situation. It is not scientifically rational to base the definition on follicular size, and the definition ignores the vast corporate knowledge acquired from the many decades and >6000 publications in animal research that universally practices IVM as per the existing definition. Furthermore, such a definition can lead to false results in interpreting the follow-up of children conceived using IVM. Hence, we see no rationale to change the existing definition of IVM. However, we agree that variations on IVM require alternative nomenclature-these definitions need to be intuitive and need to clearly distinguish themselves from the existing long standing definition of IVM. This would help to clarify the recent confusion within the clinical ART community as to what is and what is not, IVM. PMID- 27664205 TI - IUI and IVF for unexplained subfertility: where did we go wrong? AB - IUI is a first-line treatment for couples with unexplained or mild male subfertility and has become one of the most widely used fertility-enhancing treatments. The results of a recent trial comparing IVF to IUI, demonstrating similar live birth rates, have been used to build a case supporting the effectiveness of IUI. Yet, this conclusion might be somewhat premature, as the superiority of neither IUI nor IVF over no treatment has ever been proven. The evidence on the effectiveness and safety of IUI and IVF has been evaluated in two Cochrane reviews which both suggested that there is insufficient evidence to conclude that IUI or IVF is effective compared to sexual intercourse in couples with unexplained subfertility. Recommendations for clinical practice have been given in the most recent National Institute for Health and Care Excellence fertility guideline that advises not to offer IUI any longer and suggests 2 years of sexual intercourse followed by IVF. This recommendation has generated an ongoing debate, with only 4% of all gynecologists in the UK discontinuing the use of IUI. We feel that it is high time to provide proper scientific evidence for the effectiveness of IUI, or lack thereof, and invite the medical community to start RCTs comparing IUI to sexual intercourse. PMID- 27664207 TI - Population trends and live birth rates associated with common ART treatment strategies. AB - STUDY QUESTION: Have ART live birth rates improved in Australia over the last 12 years? SUMMARY ANSWER: There were striking improvements in per-cycle live birth rates observed for frozen/thaw embryo transfers, blastocyst transfer and single embryo transfer (SET), while live birth rates following ICSI were lower than IVF for non-male factor infertility in most years. WHAT IS ALREADY KNOWN: ART and associated techniques have become the predominant treatment of infertility over the past 30 years in most developed countries. However, there are differences in ART laboratory and clinical practices, and success rates worldwide. Australia has one of the highest ART utilization rates and lowest multiple birth rates in the world, thus providing a unique setting to investigate the contribution of common ART strategies in an unrestricted population of patients to ART success rates. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 585 065 ART treatment cycles performed in Australia between 2002 and 2013 using the Australian and New Zealand Assisted Reproduction Database (ANZARD). PARTICIPANTS MATERIALS, SETTING, METHOD: An unrestricted population of all women who underwent autologous ART treatment between 2002 and 2013. Visual descriptive analysis was used to assess the trends in ART procedures by the calendar years. Adjusted odds ratios (aORs) of a live birth for four common ART techniques were calculated after controlling for important confounders including female age, infertility diagnosis, stage of the embryo (blastocyst versus cleavage stage), type of embryo (fresh versus thawed), fertilization method (IVF versus ICSI) and number of embryos transferred (SET versus multiple embryos). MAIN RESULTS AND THE ROLE OF CHANCE: The overall live birth rate per embryo transfer increased from 19.2% in 2002 to 23.3% in 2013 (21.9-24.3% for fresh embryo transfers and 14.6-23.3% for frozen/thaw embryo transfers). This occurred concurrently with an increase in SET from 29.7% to 78.9%, and an increase in the average age of women undergoing treatment from 35.0 to 35.9 years. Individuals who had a frozen/thaw embryo transfer cycle in 2002 had 43% (aOR: 0.57, 95% CI: 0.53-0.61) reduced odds of a live birth compared with a fresh embryo transfer cycle. This contrasted with 16% (aOR: 0.84, 95% CI: 0.80-0.98) reduced odds of a live birth from frozen/thaw embryo transfer cycles in 2013. In 2013, the odds of blastocyst transfer resulting in a live birth were more than twice as great as for cleavage stage transfer (aOR 2.01, 95% CI: 1.92-2.11). The adjusted odds of live birth per SET compared with multiple embryo transfer increased significantly over the last 12 years, from a 38% reduced odds of a live birth follow SET in 2002 (aOR: 062, 95% CI: 0.57-0.67) compared to an 8% reduced odds in 2013 (aOR: 0.92, 95% CI: 0.87 0.98). The aOR of a live birth using ICSI compared to IVF in non-male factor patients was lower in most years bringing into question its widespread use. LIMITATION, REASONS FOR CAUTION: This is a retrospective cohort analysis and cannot confirm causality. High-level evidence on the effectiveness of particular ART techniques, particularly ICSI and blastocyst culture, requires prospective randomized controlled trials or detailed statistical analysis using large-scale data that counts for fertilization failure, embryo loss, prognostic factors and cycle characteristics. WIDER IMPLICATION OF THE FINDINGS: The most striking improvements in ART success rates in Australia have been observed for frozen/thaw embryo transfers, blastocyst transfer and SET. Further studies of the role of ICSI in non-male factor infertility and blastocyst transfer success rates that take into account embryo loss are needed. STUDY FUNDING/COMPETING INTERESTS: No funding was received to undertake this study. The authors declare that they do not have competing interests with this study. TRIAL REGISTRATION NUMBER: NA. PMID- 27664206 TI - Assessment of 'one-step' versus 'sequential' embryo culture conditions through embryonic genome methylation and hydroxymethylation changes. AB - STUDY QUESTION: In comparison to in vivo development, how do different conditions of in vitro culture ('one step' versus 'sequential medium') impact DNA methylation and hydroxymethylation in preimplantation embryos? SUMMARY ANSWER: Using rabbit as a model, we show that DNA methylation and hydroxymethylation are both affected by in vitro culture of preimplantation embryos and the effect observed depends on the culture medium used. WHAT IS KNOWN ALREADY: Correct regulation of DNA methylation is essential for embryonic development and DNA hydroxymethylation appears more and more to be a key player. Modifications of the environment of early embryos are known to have long term effects on adult phenotypes and health; these probably rely on epigenetic alterations. STUDY DESIGN SIZE, DURATION: The study design we used is both cross sectional (control versus treatment) and longitudinal (time-course). Each individual in vivo experiment used embryos flushed from the donor at the 2-, 4-, 8-, 16- or morula stage. Each stage was analyzed in at least two independent experiments. Each individual in vitro experiment used embryos flushed from donors at the 1-cell stage (19 h post-coitum) which were then cultured in parallel in the two tested media until the 2-, 4-, 8- 16-cell or morula stages. Each stage was analyzed in at least three independent experiments. In both the in vivo and in vitro experiments, 4-cell stage embryos were always included as an internal reference. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunofluorescence with antibodies specific for 5-methylcytosine (5meC) and 5-hydroxymethylcytosine (5hmeC) was used to quantify DNA methylation and hydroxymethylation levels in preimplantation embryos. We assessed the expression of DNA methyltransferases (DNMT), of ten eleven translocation (TET) dioxigenases and of two endogenous retroviral sequences (ERV) using RT-qPCR, since the expression of endogenous retroviral sequences is known to be regulated by DNA methylation. Three repeats were first done for all stages; then three additional repetitions were performed for those stages showing differences or tendencies toward differences between the different conditions in the first round of quantification. MAIN RESULTS AND THE ROLE OF CHANCE: The kinetics of DNA methylation and hydroxymethylation were modified in in vitro cultured embryos, and the observed differences depended on the type of medium used. These differences were statistically significant. In addition, the expression of TET1 and TET2 was significantly reduced in post-embryonic genome activation (EGA) embryos after in vitro culture in both tested conditions. Finally, the expression of two retroviral sequences was analyzed and found to be significantly affected by in vitro culture. LIMITATIONS REASONS FOR CAUTION: Our study remains mostly descriptive as no direct link can be established between the epigenetic changes observed and the expression changes in both effectors and targets of the studied epigenetic modifications. The results we obtained suggest that gene expression could be affected on a large scale, but this remains to be confirmed. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in agreement with the literature, showing that DNA methylation is sensitive to in vitro culture. As we observed an effect of both tested culture conditions on the tested epigenetic marks and on gene expression, we cannot conclude which medium is potentially closest to in vivo conditions. However, as the observed effects are different, additional studies may provide more information and potential recommendations for the use of culture media in assisted reproductive technology. STUDY FUNDING/COMPETING INTERESTS: This work was supported by an 'AMP diagnostic prenatal et diagnostic genetique' 2012 grant from the French Agence de la Biomedecine. This study was performed within the framework of ANR LABEX 'REVIVE' (ANR-10-LABX-73). Authors are members of RGB-Net (TD 1101) and Epiconcept (FA 1201) COST actions. The authors declare that there is no competing interest. PMID- 27664208 TI - Factors associated with ovarian function recovery after chemotherapy for breast cancer: a systematic review and meta-analysis. AB - STUDY QUESTION: Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer? SUMMARY ANSWER: Younger age and GnRH agonist (GnRHa) administration during chemotherapy were significantly associated with menses recovery, but this recovery was less likely in patients exposed to taxanes. WHAT IS ALREADY KNOWN: To date, published meta-analyses have only assessed GnRHa administration as a possible factor for ovarian function recovery, and their results were conflicting. Current guidelines present distinct recommendations regarding the use of GnRHa for fertility preservation (FP) in women with breast cancer. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of published studies in the English, Portuguese, French or Spanish languages (1990 2015), ongoing trials or completed trials (1990-2015) and conference proceedings (2000-2015) were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched the MEDLINE, Embase, LILACS, Scielo, Toxline and DART databases, online trial registries and conference proceedings. Studies were eligible if they included premenopausal women with early breast cancer treated with chemotherapy, reported ovarian function recovery data and identified factor(s) associated with recovery. Two authors independently screened the studies, extracted data and assessed the risk of bias. An odds ratio (OR) was estimated from the number of recovery events. A meta-analysis was conducted using a random-effects model. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen articles were included. Five different factors were analysed: younger age and baseline levels of anti-Mullerian hormone (patient related factors), co-administration of GnRHa, addition of taxanes to anthracycline-based chemotherapy and addition of endocrine therapy to chemotherapy (treatment-related factors). Menses recovery was the most used marker. Younger age (<=40 years) and exposure to GnRHa were positively associated with menses recovery (OR 6.07 and 2.03, respectively) but exposure to taxanes adversely affected recovery (OR 0.49). Significant heterogeneity among studies was found. LIMITATIONS, REASONS FOR CAUTION: A general limitation of the included studies is the use of menses as the main recovery marker. Regarding GnRHa, the substantial heterogeneity and conflicting results limit the interpretation of our results. Studies that use additional markers and have a longer follow-up are needed. WIDER IMPLICATIONS OF THE FINDINGS: The decision for using chemotherapy regimens with taxanes must take into account their potential adverse effects on female fertility. Considering the conflicting results regarding GnRHa agonist use, other fertility preservation strategies should also be considered. STUDY FUNDING/COMPETING INTERESTS: No external funding was received. There are no conflicts of interest to declare. PROSPERO REGISTRATION NUMBER: This review was registered at PROSPERO (CRD42015013494). PMID- 27664209 TI - Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and association with late miscarriage. AB - STUDY QUESTION: Are novel circulating placental markers prokineticin-1 (PK-1), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) associated with late miscarriage in asymptomatic first trimester pregnant women? SUMMARY ANSWER: Increased serum sFlt-1 or PlGF, but not sEng or PK-1, were significantly associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure. WHAT IS KNOWN ALREADY: Abnormal placental development is observed in two-thirds of miscarriages. Identifying women at high risk of late miscarriage could help diagnose potentially treatable causes of miscarriage such as infection, thrombosis or immunological disease. Recently, the circulating placental markers PK-1, sFlt-1, sEng and PlGF have been identified; however, it is not known if circulating levels of these markers are associated with late miscarriage. STUDY DESIGN, SIZE, DURATION: A single-centre observational cohort study with prospectively collected data was carried out at a tertiary care centre 2010-2012, in 993 asymptomatic pregnant women. Plasma PK-1, and serum sEng, sFlt-1 and PlGF were measured once in each patient during the antenatal booking visit, and pregnancy outcome was monitored prospectively. Less than 1% of patients were lost to follow-up. Multiples of median (MOM) levels were calculated to adjust for gestational age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine-hundred and ninety-three asymptomatic pregnant women attending antenatal clinic for a routine booking antenatal appointment were recruited to the study, of whom 12 were lost to follow-up and excluded from analysis. Of the cohort, 50 of the remaining 981 women suffered late miscarriage. MAIN RESULTS AND THE ROLE OF CHANCE: Gestation adjusted sEng, sFlt-1 and PlGF levels were 11% (P < 0.01), 36% (P < 0.001) and 30% (P < 0.001), respectively, lower in women who later suffered miscarriage compared with unaffected pregnancies, while PK-1 did not differ significantly. Logistic regression modelling suggested that increased sFlt-1 (odds ratio (OR) 0.15 95% confidence interval [0.08-0.26], P = 0.0001) and PlGF (OR 0.02 [0.01 0.05], P = 0.0001), but not sEng, were associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure. The combination of sFlt-1 and PlGF did not improve the diagnostic accuracy beyond the use of sFlt-1. LIMITATIONS, REASONS FOR CAUTION: First trimester levels of sFlt-1 and PlGF, but not sEng or PK-1, were associated with late miscarriage risk in asymptomatic women. However, a new prospective study is now required to investigate the utility of these markers to predict early (<10 weeks) and late miscarriage, as well as to predict other complications of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that circulating sFlt-1 and PlGF, but not sEng or PK-1, are independently associated with late miscarriage risk in asymptomatic pregnant women attending their antenatal visit. Therefore, sFlt-1 and PlGF may represent novel markers of placental viability. These data further our understanding of placental function, and have important potential implications for utilizing novel hormonal markers to detect adverse clinical outcomes during pregnancy. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interests. The Section of Investigative Medicine is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This project was funded by an NIHR grant (reference: CDF-2009-02-05). The following authors are also funded as follows: CNJ is supported by an NIHR Clinical Lectureship and AMS/ Wellcome Starter Grant for Clinical Lecturers. AA and ANC are supported by NIHR academic clinical lectureships. CI-E is supported by an Imperial College Healthcare NHS Trust Charity Research Fellowship. WSD is supported by an NIHR Career Development Fellowship. TRIAL REGISTRATION NUMBER: Q0406/80. PMID- 27664210 TI - Comparison of small intestinal submucosa graft with split-thickness skin graft for cervicovaginal reconstruction of congenital vaginal and cervical aplasia. AB - STUDY QUESTION: What is the difference in vaginal-length gain and resumption of menstruation following cervicovaginal reconstruction using split-thickness skin (STS) graft versus small intestinal submucosa (SIS) graft for patients with congenital vaginal and cervical aplasia? SUMMARY ANSWER: No difference was found in the number of patients who resumed menstruation between the two groups; however, significantly greater vaginal-length gain was found in the STS group. WHAT IS ALREADY KNOWN: Hysterectomy and vaginoplasty are typically recommended for patients without a cervix or without a sufficient cervix to avoid postoperative re-obstruction. Advances in surgical techniques have enabled the use of autologous tissues or heterologous biological grafts for reconstructive procedures, allowing patients undergoing these procedures to preserve the possibility of conception. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of 26 women who were diagnosed with congenital vaginal and cervical aplasia with a functional endometrial cavity and underwent cervicovaginal reconstruction using STS or SIS grafts between January 2012 and October 2015 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PARTICIPANTS/MATERIALS, SETTING, METHOD: 15 women underwent cervicovaginal reconstruction using SIS graft and 11 underwent cervicovaginal reconstruction using STS graft. Clinical characteristics, perioperative data, resumption of menstruation, vaginal stenosis, length of the neovagina, vaginal-length gain, stricture of the cervix and body image were postoperatively assessed. MAIN RESULTS AND THE ROLE OF CHANCE: At a median follow-up of 21 (2-46) months, all but one of the patients experienced relief of abdominal pain and resumed menstruation. Re-obstruction of the cervix occurred in only one patient in the SIS group. The SIS group reported significantly higher body image scores and cosmetic satisfaction. Although the two groups had a similar vaginal length before surgery, the vaginal-length gain was significantly greater in the STS group (4.9 +/- 1.7 cm in the SIS group versus 7.5 +/- 0.7 cm in the STS group, P = 0.004) and the neovagina length at 6 months post-operation was significantly shorter in the SIS group (6.5 +/- 0.7 cm in SIS the group versus 8.0 +/- 0.5 cm in the STS group, P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: Due to a lack of long-term follow-up, patient satisfaction with sex life, pregnancy rates and outcomes after the two approaches require further evaluation. WIDER IMPLICATIONS OF THE FINDINGS: Combined laparoscopic and vaginal cervicovaginal reconstruction using SIS or STS graft is a safe and effective treatment for preserving uterus function in women with congenital vaginal and cervical aplasia. However, SIS graft must still be improved to achieve satisfactory vaginal length. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A. PMID- 27664211 TI - Do ARTs affect the incidence of monozygotic twinning? AB - STUDY QUESTION: Does the manipulation of gametes or embryos during ARTs increase the risk for monozygotic twinning (MZT)? SUMMARY ANSWER: Frozen embryo transfer (ET) is associated with a lower MZT rate, while blastocyst culture is associated with an increased risk of monozygotic pregnancy. WHAT IS KNOWN ALREADY: Monozygotic twins have a higher risk for perinatal complications. Although an increased incidence of monozygotic pregnancies after ART has been previously reported, data regarding the possible impact of different laboratory procedures are conflicting. STUDY DESIGN, SIZE, DURATION: All clinical pregnancies after single ET carried out in our centre between 2004 and 2013 (n = 6096) were retrospectively analysed for the incidence of MZT. The effect of different laboratory procedures on the incidence of MZT was evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The following ART risk factors were assessed: maternal age, type of ET (fresh versus frozen), zona pellucida (ZP) manipulation (specifically, ICSI, embryo biopsy and assisted hatching), use of donor oocytes, embryo stage at time of ET (cleavage, compaction, early or advanced blastocyst) and culture media. MAIN RESULTS AND THE ROLE OF CHANCE: The overall MZT rate was 2.2% (136/6096). Frozen ET was associated with a significant reduction in MZT incidence (adjusted odds ratio (aOR) 0.48, 95% CI 0.29-0.80), while blastocyst transfer (early or advanced blastocyst) was associated with a significant increase in MZT risk (aOR 2.70, 95% CI 1.36-5.34; aOR 2.05, 95% CI 1.29-3.26, respectively). No significant differences were found between the MZT and singleton (non-MZT) groups regarding maternal age, the use of different ZP manipulation techniques, not type of culture media used. LIMITATION, REASONS FOR CAUTION: This study is limited by its retrospective nature and the fact that monozygosity was not confirmed by genetic testing. Furthermore, since monozygotic pregnancy is a rare event, other ART parameters that may influence its incidence could not be assessed during our analysis. WIDER IMPLICATION OF THE FINDINGS: Our findings warrant future studies designed to investigate the association between specific ART procedures and MZT, namely the potential risk of blastocyst transfer to increase MZT. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. There are no conflicts of interest. PMID- 27664212 TI - P-values and reproductive health: what can clinical researchers learn from the American Statistical Association? PMID- 27664213 TI - Should we individualize lipid profiling in women with polycystic ovary syndrome? AB - STUDY QUESTION: Is it necessary to monitor lipid profiles in all young women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lipid profiling is required when women with PCOS develop type 2 diabetes (T2D) or hypertension, but rarely changes clinical care before the age of 35 years. WHAT IS KNOWN ALREADY: PCOS consensus statements and guidelines recommend that women with PCOS should be screened for dyslipidaemia every second year or annually. STUDY DESIGN, SIZE, DURATION: Women from Denmark, Norway, Finland and Sweden, who had participated in research projects or clinical trials or in whom lipid profiles had been determined routinely as part of clinical care since 2000 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: One thousand three hundred and twenty seven women with PCOS (Rotterdam criteria) were included. Based on individual cardiovascular risk score and lipid levels, treatment level was guided by the European Society of Cardiology and the European Atherosclerosis Society Task Force for the management of dyslipidaemias. Change in clinical care was defined as need to (i) immediately start statin treatment or (ii) consider statin treatment if life-style intervention fails. MAIN RESULTS AND THE ROLE OF CHANCE: All in all, 74 (5.6%) women with PCOS should immediately start statin treatment, and statin treatment should be considered in 33 women (2.5%). Among women with T2D, 27/28 (96.4%) should initiate statin treatment and the corresponding number for women with hypertension was 42/57 (73.7%). In PCOS women who had not yet developed T2D or hypertension, lipid profiling only changed clinical care in 28 (2.3%). This number was further reduced to 12 (1.2%) in women below the age of 35 years, and to zero in normal-weight women below the age of 35 years. LIMITATIONS, REASONS FOR CAUTION: Findings can only be generalized to countries with low cardiovascular mortality rates. WIDER IMPLICATIONS OF THE FINDINGS: Lipid profiling is required when women with PCOS develop T2D or hypertension. However, lipid profiling rarely changes the clinical care of low risk PCOS patients before the age of 35, especially in the normal-weight women. STUDY FUNDING/COMPETING INTERESTS: The Academy of Finland, Sigrid Juselius Foundation and the Nordic Federation of Obstetrics and Gynecology. There are no conflicts of interest to be declared. PMID- 27664214 TI - No common denominator: a review of outcome measures in IVF RCTs. AB - STUDY QUESTION: Which outcome measures are reported in RCTs for IVF? SUMMARY ANSWER: Many combinations of numerator and denominator are in use, and are often employed in a manner that compromises the validity of the study. WHAT IS KNOWN ALREADY: The choice of numerator and denominator governs the meaning, relevance and statistical integrity of a study's results. RCTs only provide reliable evidence when outcomes are assessed in the cohort of randomised participants, rather than in the subgroup of patients who completed treatment. STUDY DESIGN, SIZE, DURATION: Review of outcome measures reported in 142 IVF RCTs published in 2013 or 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Trials were identified by searching the Cochrane Gynaecology and Fertility Specialised Register. English language publications of RCTs reporting clinical or preclinical outcomes in peer reviewed journals in the period 1 January 2013 to 31 December 2014 were eligible. Reported numerators and denominators were extracted. Where they were reported, we checked to see if live birth rates were calculated correctly using the entire randomised cohort or a later denominator. MAIN RESULTS AND THE ROLE OF CHANCE: Over 800 combinations of numerator and denominator were identified (613 in no more than one study). No single outcome measure appeared in the majority of trials. Only 22 (43%) studies reporting live birth presented a calculation including all randomised participants or only excluding protocol violators. A variety of definitions were used for key clinical numerators: for example, a consensus regarding what should constitute an ongoing pregnancy does not appear to exist at present. LIMITATIONS, REASONS FOR CAUTION: Several of the included articles may have been secondary publications. Our categorisation scheme was essentially arbitrary, so the frequencies we present should be interpreted with this in mind. The analysis of live birth denominators was post hoc. WIDER IMPLICATIONS OF THE FINDINGS: There is massive diversity in numerator and denominator selection in IVF trials due to its multistage nature, and this causes methodological frailty in the evidence base. The twin spectres of outcome reporting bias and analysis of non-randomised comparisons do not appear to be widely recognised. Initiatives to standardise outcome reporting, such as requiring all effectiveness studies to report live birth or cumulative live birth, are welcome. However, there is a need to recognise that early outcomes of treatment, such as stimulation response or embryo quality, may be appropriate choices of primary outcome for early phase studies. STUDY FUNDING/COMPETING INTERESTS: J.W. is funded by a Doctoral Research Fellowship from the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. J.W. also declares that publishing research is beneficial to his career. J.W. and A.V. are statistical editors, and M.S. is Information Specialist, for the Cochrane Gynaecology and Fertility Group, although the views expressed here are not necessarily those of the group. D.R.B. is funded by the NHS as Scientific Director of a clinical IVF service. The authors declare no other conflicts of interest. PMID- 27664215 TI - A longitudinal study investigating the role of decisional conflicts and regret and short-term psychological adjustment after IVF treatment failure. AB - STUDY QUESTION: What is the relationship between decisional conflict, decisional regret and psychological well-being in women following unsuccessful IVF cycles? SUMMARY ANSWER: The mediating effect of decisional regret on the relationship between decisional conflict and fertility-related quality of life (FRQOL) has been found to be moderated by the availability (versus absence) of frozen embryos after an unsuccessful IVF cycle. WHAT IS KNOWN ALREADY: Infertility treatment is marked by its open-ended nature. Stresses in treatment decision-making could be aggravated by a culture which honours families through procreation. While studies have investigated treatment-related decision-making among infertile women, little is known about the mental health consequences of decisional conflict and decisional regret following an unsuccessful IVF cycle. STUDY DESIGN, SIZE, DURATION: A study was conducted over a 3-month period with infertile women who had recently experienced a failed IVF cycle (T0). Decisional conflict when they decided on terminating or continuing treatment (T1) and decisional regret 3 months later (T2) were measured. Participants reported their levels of depression, anxiety and FRQOL at three time points. A total of 151 participants completed all time points (attrition rate: 39%). The average age of participants was 37.2 years, and they had had 1.1 cycles (range: 0-8) on average at the time of study intake. The duration of the study was 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were infertile women who were not pregnant following an IVF cycle recruited from a university-affiliated assisted reproduction centre. Following the notification of a negative pregnancy result, patients were invited to complete measures of FRQOL, depression and anxiety across three time points and decisional conflict and decisional regret at T1 and T2 respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Decisional regret partially mediated the effect of decisional conflict on overall and treatment-specific FRQOL (P < 0.05). The mediation by decisional regret was present only among participants who had no remaining frozen embryos after their unsuccessful IVF cycle (P < 0.05). LIMITATIONS, REASON FOR CAUTION: Self-selection bias at recruitment remains a concern. WIDER IMPLICATIONS OF THE FINDINGS: Our results show for the first time how mental health implications of decisional conflict may vary among patients with different clinical characteristics (i.e. availability of frozen embryos), despite their common experience of an unsuccessful IVF cycle. Healthcare professionals should be aware of the psychological ramifications of treatment decision-making difficulties, as well as individual differences in adjustment to unsuccessful treatment. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Hong Kong University Grant Council-General Research Fund (HKU740613) and the authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: HKU Clinical Trials Registry (Trial registration number: HKUCTR-1680). PMID- 27664216 TI - The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. AB - STUDY QUESTION: What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)? SUMMARY ANSWER: The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. WHAT IS ALREADY KNOWN: PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms 'PCOS', 'polycystic ovarian disease', 'Stein Leventhal syndrome', 'Androgen Excess Society', 'National Institute of Health', 'Rotterdam', 'ESHRE/ASRM', 'criteria' and 'prevalence'. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5-8%, n = 3 trials), 9% (7-12%, n = 6 trials) and 10% (7-14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo anovulation were 13% (8-20%, n = 14 trials), 11% (8-15%, n = 9 trials), 28% (22 35%, n = 12 trials) and 15% (12-18%, n = 19 trials), respectively. LIMITATIONS, REASONS FOR CAUTION: The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts. WIDER IMPLICATIONS OF THE FINDINGS: Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe. STUDY FUNDING/COMPETING INTERESTS: No funding to declare. The authors have no conflicts of interest to declare. REGISTRATION NUMBER: None. PMID- 27664217 TI - Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial. AB - STUDY QUESTION: Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? SUMMARY ANSWER: A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. WHAT IS ALREADY KNOWN: The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. STUDY DESIGN SIZE, DURATION: This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. MAIN RESULTS AND THE ROLE OF CHANCE: Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the +/-5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. LIMITATIONS, REASONS FOR CAUTION: For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. WIDER IMPLICATIONS OF THE FINDINGS: Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials number NCT01920022. TRIAL REGISTRATION DATE: 06 August 2013. DATE OF FIRST PATIENT'S ENROLMENT: 13 October 2013. PMID- 27664218 TI - Autologous menstrual blood-derived stromal cells transplantation for severe Asherman's syndrome. AB - STUDY QUESTION: Does autologous transplantation of menstrual blood-derived stromal cells (menSCs) regenerate endometrium to support pregnancy in patients with severe Asherman's syndrome (AS)? SUMMARY ANSWER: Autologous menSCs transplantation significantly increases endometrial thickness (ET) for women with severe AS. WHAT IS KNOWN ALREADY: AS is a major cause of secondary infertility in women. Cell transplantation has been tried in a few clinical cases with encouraging results. STUDY DESIGN, SIZE, DURATION: In this experimental, non controlled and prospective 3-year clinical study involving seven patients with AS, autologous menSCs were isolated and cultured from menstrual blood of each patient within ~2 weeks and then transplanted back into their uterus. Endometrial growth and pregnancy were assessed after cell therapy. PARTICIPANTS/MATERIALS, SETTING, METHOD: Infertile women, aged 20-40 years, diagnosed with severe AS (Grade III-V) by hysteroscopy and with menstrual fluid were recruited at the Shengjing Hospital affiliated to China Medical University. Autologous menSCs transplantation was conducted followed by HRT. Endometrial thickness was monitored with frozen embryo transfer (FET) as needed. MAIN RESULTS AND THE ROLE OF CHANCE: We successfully cultured menSCs from seven patients and transferred the autologous cells back to their uterus. Our results showed that the ET was significantly (P = 0.0002) increased to 7 mm in five women, which ensured embryo implantation. Four patients underwent FET and two of them conceived successfully. One patient had spontaneous pregnancy after second menSCs transplantation. LIMITATIONS, REASONS FOR CAUTION: Limited sample size, lack of rigorous controls or knowledge of underlying mechanism. WIDER IMPLICATIONS OF THE FINDINGS: Autologous menSCs transplantation is a potential option for treating women with severe AS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Liaoning Provincial Science and Technology Program. The sponsor and authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered in the Chinese Clinical Trial Registry (ChiCTR-ONB-15007464). PMID- 27664219 TI - A novel method for crosstalk analysis of biological networks: improving accuracy of pathway annotation. AB - Analyzing gene expression patterns is a mainstay to gain functional insights of biological systems. A plethora of tools exist to identify significant enrichment of pathways for a set of differentially expressed genes. Most tools analyze gene overlap between gene sets and are therefore severely hampered by the current state of pathway annotation, yet at the same time they run a high risk of false assignments. A way to improve both true positive and false positive rates (FPRs) is to use a functional association network and instead look for enrichment of network connections between gene sets. We present a new network crosstalk analysis method BinoX that determines the statistical significance of network link enrichment or depletion between gene sets, using the binomial distribution. This is a much more appropriate statistical model than previous methods have employed, and as a result BinoX yields substantially better true positive and FPRs than was possible before. A number of benchmarks were performed to assess the accuracy of BinoX and competing methods. We demonstrate examples of how BinoX finds many biologically meaningful pathway annotations for gene sets from cancer and other diseases, which are not found by other methods. BinoX is available at http://sonnhammer.org/BinoX. PMID- 27664220 TI - Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation. AB - It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks determine the levels of transcription of a given gene at a given time. Using three complementary computational techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are constrained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any requirement for external signalling factors. Our models combine atomistic molecular dynamics (MD) with coarse-grained simulations and statistical mechanical calculations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denaturation in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informational transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles. PMID- 27664223 TI - Erratum: Utilisation of the falciform ligament pedicle flap as an alternative approach for the repair of a perforated gastric ulcer. PMID- 27664224 TI - Erratum: Prevascular femoral hernia and its relation with inferior epigastric vessels: a rare presentation of the femoral hernia sac. PMID- 27664225 TI - Non-tuberculous mycobacteria mimic of MDR-TB infection in Pott's disease. AB - A 34 year-old woman presented with history of progressive back pain which was diagnosed as Pott's disease with recurrent paravertebral abscess, and had received a total of 23 months of antitubercular treatment for lumbar infection. The patient was non-responsive to treatment and was referred to a higher centre where the infection was finally identified as non-tuberculous mycobacterium (Mycobacterium fortuitum) by genotypic testing. The drugs were initiated according to results of drug susceptibility testing by the broth microdilution method. We describe here an unusual case of M. fortuitum infection that presented as Pott's disease identified by molecular test which was followed by treatment and successful cure of the disease. PMID- 27664222 TI - A Pap1-Oxs1 signaling pathway for disulfide stress in Schizosaccharomyces pombe. AB - We describe a Pap1-Oxs1 pathway for diamide-induced disulfide stress in Schizosaccharomyces pombe, where the nucleocytoplasmic HMG protein Oxs1 acts cooperatively with Pap1 to regulate transcription. Oxs1 and Pap1 form a complex when cells are exposed to diamide or Cd that causes disulfide stress. When examined for promoters up-regulated by diamide, effective Pap1 binding to these targets requires Oxs1, and vice versa. With some genes, each protein alone enhances transcription, but the presence of both exerts an additive positive effect. In other genes, although transcription is induced by diamide, Oxs1 or Pap1 plays a negative role with full de-repression requiring loss of both proteins. In a third class of genes, Oxs1 positively regulates expression, but in its absence, Pap1 plays a negative role. The Oxs1-Pap1 regulatory interaction appears evolutionarily conserved, as heterologous (human, mouse and Arabidopsis) Oxs1 and Pap1-homologues can bind interchangeably with each other in vitro, and at least in the fission yeast, heterologous Oxs1 and Pap1-homologues can substitute for S. pombe Oxs1 and Pap1 to enhance stress tolerance. PMID- 27664226 TI - Enoxaparin-induced hepatotoxicity: an under-recognised complication of enoxaparin therapy. AB - Low-molecular-weight heparins including enoxaparin are commonly used for anticoagulation as prophylaxis and treatment for deep vein thrombosis (DVT). Prescribers of enoxaparin monitor for common side effects, such as bleeding and thrombocytopenia, but hepatotoxicity, a less common and under-reported adverse effect, may be overlooked. This report describes a case of enoxaparin-induced hepatotoxicity in a 57-year-old man who was started on the drug for a DVT. Within 3 days of taking enoxaparin, elevated transaminases were noted, and the drug was discontinued after 6 days. Similar to other published reports, the patient's transaminases peaked 1 day after discontinuation of the drug and then trended down to normal over 32 days. PMID- 27664227 TI - Cardiac tamponade as a manifestation of severe dermatomyositis. AB - In connective tissue disorders, the incidence of pericardial disease and pericardial effusion can be up to 58%, and if untreated, it can lead to cardiac tamponade which can be fatal. Physicians must have a high index of suspicion for this disease as diagnosis can be delayed while evaluating more common causes of tachycardia and hypotension in the immunosuppressed (ie, sepsis). We present a 55 year-old woman with a severe case of dermatomyositis, marked by significant weight loss, a bedridden state and hallmark cutaneous findings. On evaluation of interstitial lung disease, a pericardial effusion was incidentally noted. Serial examination revealed increasing fluid accumulation and progressive tachycardia, and diagnosis of cardiac tamponade was made on echocardiography. After initial pericardiocentesis, the effusion rapidly re-accumulated requiring a pericardial window. In severe presentations of rheumatic disease, cardiac tamponade should be considered as a cause of tachycardia, with or without associated hypotension. PMID- 27664228 TI - Management of postvitrectomy retinal detachment due to multiple laser-induced retinal holes. AB - A 25-year-old man presented with retinal detachment in his right eye 20 days after pars plana vitrectomy, epiretinal membrane peeling and endolaser assisted panretinal photocoagulation performed for non-resolving vitreous haemorrhage secondary to Eales disease. Inferior retina of the right eye showed multiple (around 120) retinal holes in relation to the previous photocoagulation marks. The patient was managed with repeat vitrectomy, endolaser and silicone oil infusion. The aetiology of multiple holes, precautions to prevent them and their management are described. PMID- 27664229 TI - Rare case of Corynebacterium striatum septic arthritis. AB - Corynebacterium species are aerobic, Gram-positive bacilli that are commensal organisms of skin and mucosal membranes. Although its pathogenicity is well established, Corynebacterium striatum is frequently isolated in cultures and generally regarded as a contaminant. Rarely, this bacterium causes septic arthritis. We present a case of right shoulder joint septic arthritis due to C. striatum in a lung-transplant recipient with end-stage renal disease. A brief review of the literature regarding C. striatum septic arthritis is also a part of this report. PMID- 27664230 TI - Faecal microbiota transplantation for recurring Clostridium difficile infection in a patient with Crohn's disease and ileorectal anastomosis. AB - Faecal microbiota transplantation (FMT) is increasingly being used to treat refractory and recurring Clostridium difficile infection (CDI). Although FMT appears to be safe and highly effective in patients with a preserved colon and immunocompetence, its use in patients with inflammatory bowel disease (IBD) who are on immunomodulating therapies is controversial. In particular, patients who have undergone colectomy may have different treatment responses to FMT. In this case report, we describe the successful use of FMT in a female patient aged 19 years with Crohn's disease who underwent ileorectal anastomosis following colectomy. She had recurrent CDIs that were refractory to metronidazole, pulse tapered vancomycin and fidaxomicin treatments. She underwent 2 FMTs, which were performed via sigmoidoscopy; her mother served as a donor. Follow-up was conducted for 12 months and indicated sustained remission of CDI. PMID- 27664231 TI - Miliarial gout: a rare presentation of extensive cutaneous tophi. AB - Gout is a systemic disorder characterized by hyperuricemia and recurrent arthritis, most involvement of ankles, midfoot joint and first metatarsophalangeal joint, with monosodium urate crystals deposition in synovial fluid and other tissues. We present a case of 53-year-old male, who had several nontender, white-yellow papules and plaques over his elbows, knees and arms with chalk-like substances and crust on inflammatory base wax and wane in the past 2 years. Upon histopathology examination of the skin lesions, it reported as intradermal urate tophi and miliarial gout was diagnosed. This case highlights the importance of considering unusual cutaneous tophi in the differential diagnosis of deposition disorders. PMID- 27664233 TI - 'Cold cuts' added to the circadian smorgasbord of regulatory mechanisms. AB - In mammals, rhythms in body temperature help to entrain and synchronize circadian rhythms throughout the organism, and the cold-inducible RNA-binding protein (CIRBP) is one of the mediators of these daily temperature changes. Cirbp mRNA expression is regulated by the daily subtle rhythms in body temperature, and a new study by Gotic and colleagues (pp. 2005-2017) reveals a surprising and novel mechanism that involves temperature-dependent enhancement of splicing efficiency. PMID- 27664232 TI - Effectiveness of cardiogoniometry compared with exercise-ECG test in diagnosing stable coronary artery disease in women. AB - Aims: To investigate the effectiveness of cardiogoniometry, a novel, non-invasive method, in diagnosing coronary artery disease (CAD) in women and compare it with exercise-ECG test, by using coronary angiography as a reference method. Methods: It was a single-centre, case-series study including consecutive female patients with stable angina pectoris (AP) undergoing coronary angiography. Exercise-ECG test, done according to the Bruce protocol, and cardiogoniometry were obtained prior to coronary angiography. Clinically significant CAD has been defined as one or more coronary lesions with >70% stenosis. Results: Study included 114 consecutive female patients with median age of 64.0 (58.0-71.0) years, out of which 32 (28.1%) had CAD. Cardiogoniometry yielded a total accuracy of 74.6% with a sensitivity of 75.0% (95% CI 56.6-88.5) and specificity of 74.4% (95% CI 63.6 83.4). Exercise-ECG test yielded a total accuracy of 45.1% with a sensitivity of 68.1% (95% CI 42.7-83.6) and specificity 36.6% (95% CI 25.2-50.3). Cardiogoniometry showed higher accuracy than exercise-ECG test ( P < 0.001). Pathological cardiogoniometry was associated with almost nine times higher risk for CAD (OR 8.7, 95%CI 3.4-22.3, P < 0.001), which remained significant after adjustment for age, and hypokinesia. Conclusion: Cardiogoniometry is a non invasive, easy-to-use and free-of-risk method which showed high effectiveness in diagnosing stable CAD in women and superior to exercise-ECG test. Cardiogoniometry could be introduced as a part of the diagnostic algorithm of screening women for stable CAD and is suitable for use in the primary setting, especially in women unable to undergo stress-testing. PMID- 27664234 TI - Pancreatic fibroblasts smoothen their activities via AKT-GLI2-TGFalpha. AB - Pancreatic stromal fibroblasts provide structural support. Activated fibroblasts are critical in the tumor microenvironment. In this issue of Genes & Development, Liu and colleagues (pp. 1943-1955) unravel the finding that depletion of Smoothened (Smo) in pancreatic stromal fibroblasts results in AKT activation and noncanonical GLI2 activation with subsequent TGFalpha secretion, activation of EGFR in pancreatic epithelial cells, and augmentation of acinar-ductal metaplasia. Additionally, Smo-mediated signaling has proproliferative effects on pancreatic tumor cells. PMID- 27664235 TI - Recent insights into the function of autophagy in cancer. AB - Macroautophagy (referred to here as autophagy) is induced by starvation to capture and degrade intracellular proteins and organelles in lysosomes, which recycles intracellular components to sustain metabolism and survival. Autophagy also plays a major homeostatic role in controlling protein and organelle quality and quantity. Dysfunctional autophagy contributes to many diseases. In cancer, autophagy can be neutral, tumor-suppressive, or tumor-promoting in different contexts. Large-scale genomic analysis of human cancers indicates that the loss or mutation of core autophagy genes is uncommon, whereas oncogenic events that activate autophagy and lysosomal biogenesis have been identified. Autophagic flux, however, is difficult to measure in human tumor samples, making functional assessment of autophagy problematic in a clinical setting. Autophagy impacts cellular metabolism, the proteome, and organelle numbers and quality, which alter cell functions in diverse ways. Moreover, autophagy influences the interaction between the tumor and the host by promoting stress adaptation and suppressing activation of innate and adaptive immune responses. Additionally, autophagy can promote a cross-talk between the tumor and the stroma, which can support tumor growth, particularly in a nutrient-limited microenvironment. Thus, the role of autophagy in cancer is determined by nutrient availability, microenvironment stress, and the presence of an immune system. Here we discuss recent developments in the role of autophagy in cancer, in particular how autophagy can promote cancer through suppressing p53 and preventing energy crisis, cell death, senescence, and an anti-tumor immune response. PMID- 27664236 TI - Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. AB - Increased lipid synthesis is a key characteristic of many cancers that is critical for cancer progression. ATP-citrate lyase (ACLY), a key enzyme for lipid synthesis, is frequently overexpressed or activated in cancer to promote lipid synthesis and tumor progression. Cullin3 (CUL3), a core protein for the CUL3-RING ubiquitin ligase complex, has been reported to be a tumor suppressor and frequently down-regulated in lung cancer. Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. Through negative regulation of ACLY, CUL3 inhibits lipid synthesis, cell proliferation, and xenograft tumor growth of lung cancer cells. Furthermore, ACLY inhibitor SB-204990 greatly abolishes the promoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth. Importantly, low CUL3 expression is associated with high ACLY expression and poor prognosis in human lung cancer. In summary, our results identify CUL3-KLHL25 ubiquitin ligase as a novel negative regulator for ACLY and lipid synthesis and demonstrate that decreased CUL3 expression is an important mechanism for increased ACLY expression and lipid synthesis in lung cancer. These results also reveal that negative regulation of ACLY and lipid synthesis is a novel and critical mechanism for CUL3 in tumor suppression. PMID- 27664238 TI - Cap-independent translation by DAP5 controls cell fate decisions in human embryonic stem cells. AB - Multiple transcriptional and epigenetic changes drive differentiation of embryonic stem cells (ESCs). This study unveils an additional level of gene expression regulation involving noncanonical, cap-independent translation of a select group of mRNAs. This is driven by death-associated protein 5 (DAP5/eIF4G2/NAT1), a translation initiation factor mediating IRES-dependent translation. We found that the DAP5 knockdown from human ESCs (hESCs) resulted in persistence of pluripotent gene expression, delayed induction of differentiation associated genes in different cell lineages, and defective embryoid body formation. The latter involved improper cellular organization, lack of cavitation, and enhanced mislocalized apoptosis. RNA sequencing of polysome associated mRNAs identified candidates with reduced translation efficiency in DAP5-depleted hESCs. These were enriched in mitochondrial proteins involved in oxidative respiration, a pathway essential for differentiation, the significance of which was confirmed by the aberrant mitochondrial morphology and decreased oxidative respiratory activity in DAP5 knockdown cells. Further analysis identified the chromatin modifier HMGN3 as a cap-independent DAP5 translation target whose knockdown resulted in defective differentiation. Thus, DAP5-mediated translation of a specific set of proteins is critical for the transition from pluripotency to differentiation, highlighting the importance of cap-independent translation in stem cell fate decisions. PMID- 27664237 TI - Superenhancer reprogramming drives a B-cell-epithelial transition and high-risk leukemia. AB - IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors. IKAROS is also highly enriched at inactive enhancers of genes normally expressed in stem-epithelial cells. Upon IKAROS loss, expression of pre-B-cell differentiation genes is attenuated, while a group of extralineage transcription factors that are directly repressed by IKAROS and depend on EBF1 relocalization at their enhancers for expression is induced. LHX2, LMO2, and TEAD-YAP1, normally kept separate from native B-cell transcription regulators by IKAROS, now cooperate directly with them in a de novo superenhancer network with its own feed forward transcriptional reinforcement. Induction of de novo superenhancers antagonizes Polycomb repression and superimposes aberrant stem-epithelial cell properties in a B-cell precursor. This dual mechanism of IKAROS regulation promotes differentiation while safeguarding against a hybrid stem-epithelial-B cell phenotype that underlies high-risk B-ALL. PMID- 27664239 TI - Corrigendum: The epidermis coordinates auxin-induced stem growth in response to shade. PMID- 27664240 TI - Reply to Bordoni et al. PMID- 27664241 TI - HIV Medicine Residency Training: Experience From Mississippi. PMID- 27664243 TI - ESMO Guidelines Committee. PMID- 27664242 TI - The Different Roles of Interleukin 7 and Interleukin 18 in Affecting Lymphoid Hematopoietic Progenitor Cells and CD4 Homeostasis in Naive Primary and Chronic HIV-Infected Patients. PMID- 27664245 TI - Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 27664246 TI - Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. PMID- 27664247 TI - Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. PMID- 27664248 TI - 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. PMID- 27664250 TI - appendix 2: Cutaneous melanoma (2): eUpdate published online September 2016 (http://www.esmo.org/Guidelines/Melanoma). PMID- 27664249 TI - appendix 1: Cutaneous melanoma (1): eUpdate published online September 2016 (www.esmo.org/Guidelines/Melanoma). PMID- 27664251 TI - appendix 3: Neuroendocrine tumours: eUpdate published online September 2016 (www.esmo.org/Guidelines/Neuroendocrine-Tumours). PMID- 27664252 TI - appendix 4: Metastatic colorectal cancer (1): eUpdate published online September 2016 (www.esmo.org/Guidelines/Gastrointestinal-Cancers). PMID- 27664253 TI - appendix 5: Metastatic colorectal cancer (2): eUpdate published online August 2016 (www.esmo.org/Guidelines/Gastrointestinal-Cancers). PMID- 27664254 TI - appendix 6: Chronic lymphocytic leukaemia: eUpdate published online September 2016 (http://www.esmo.org/Guidelines/Haematological-Malignancies). PMID- 27664255 TI - appendix 7: Ovarian cancer: eUpdate published online September 2016 (http://www.esmo.org/Guidelines/Gynaecological-Malignancies). PMID- 27664256 TI - appendix 8: Prostate cancer: eUpdate published online September 2016 (http://www.esmo.org/Guidelines/Genitourinary-Cancers). PMID- 27664257 TI - The ESMO Guidelines Committee would like to publish the following corrections to manuscripts published in 2015. PMID- 27664258 TI - ESMO Guidelines Committee Disclosures. PMID- 27664259 TI - Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 27664260 TI - Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 27664261 TI - Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 27664262 TI - Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 27664263 TI - Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 27664265 TI - Photo Quiz: Skin Lesions from a Returning Traveler. PMID- 27664264 TI - Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study. AB - OBJECTIVE: To compare long-term cardiovascular outcomes in survivors of fetal anaemia and intrauterine transfusion with those of non-anaemic siblings. DESIGN: Retrospective cohort study. SETTING: Auckland, New Zealand. PARTICIPANTS: Adults who received intrauterine transfusion for anaemia due to rhesus disease (exposed) and their unexposed sibling(s). EXPOSURE: Fetal anaemia requiring intrauterine transfusion. MAIN OUTCOME MEASURES: Anthropometry, blood pressure, lipids, heart rate variability and cardiac MRI, including myocardial perfusion. RESULTS: Exposed participants (n=95) were younger than unexposed (n=92, mean+/-SD 33.7+/ 9.3 vs 40.1+/-10.9 years) and born at earlier gestation (34.3+/-1.7 vs 39.5+/-2.1 weeks). Exposed participants had smaller left ventricular volumes (end-diastolic volume/body surface area, difference between adjusted means -6.1, 95% CI -9.7 to 2.4 mL/m2), increased relative left ventricular wall thickness (difference between adjusted means 0.007, 95% CI 0.001 to 0.012 mm.m2/mL) and decreased myocardial perfusion at rest (ratio of geometric means 0.86, 95% CI 0.80 to 0.94). Exposed participants also had increased low frequency-to-high frequency ratio on assessment of heart rate variability (ratio of geometric means 1.53, 95% CI 1.04 to 2.25) and reduced high-density lipoprotein concentration (difference between adjusted means -0.12, 95% CI -0.24 to 0.00 mmol/L). CONCLUSIONS: This study provides the first evidence in humans that cardiovascular development is altered following exposure to fetal anaemia and intrauterine transfusion, with persistence of these changes into adulthood potentially indicating increased risk of cardiovascular disease. These findings are relevant to the long-term health of intrauterine transfusion recipients, and may potentially also have implications for adults born preterm who were exposed to anaemia at a similar postconceptual age. PMID- 27664267 TI - Closing the Brief Case: Dyspnea in a Profoundly Immunocompromised Man. PMID- 27664266 TI - The Brief Case: Dyspnea in a Profoundly Immunocompromised Man. PMID- 27664268 TI - Answer to October 2016 Photo Quiz. PMID- 27664271 TI - EGFR gene copy number as a predictive/biomarker for patients with non-small-cell lung cancer receiving tyrosine kinase inhibitor treatment: a systematic review and meta-analysis. AB - Epidermal growth factor receptor (EGFR) gene copy number has been proposed as a candidate biomarker for predicting treatment response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). MEDLINE, PubMed, Cochrane, and Google Scholar databases were searched until October 21, 2015 using the following search terms: lung neoplasms/lung cancer/non-small cell lung cancer/NSCLC, EGFR, gene amplification, copy number, erlotinib, gefitinib, tyrosine-kinase inhibitor/TKI, predictor. 17 studies were included in the analysis with a total of 2047 patients. The overall analysis found that increased EGFR gene copy number was associated with higher overall response rate (ORR), overall survival (OS) and progression-free survival (PFS; p values <=0.008) compared with patients without a high EGFR gene copy number. Subgroup analysis found that in a population of patients who were primarily Caucasian, a higher EGFR gene copy number was also associated with increased ORR, OS, and PFS (p values <=0.018). The results were similar in a population of Asian patients, except that a higher EGFR gene copy number was not associated with improved OS (p=0.248). Sensitivity analysis indicated that no one study overly influenced the results and that the findings are robust. The result of the analysis found that EGFR gene copy number was associated with increased OS and PFS, supporting the idea that EGFR gene copy number is a biomarker for response to EGFR-TKI therapy in patients with advanced NSCLC. PMID- 27664272 TI - The IBD Disability Index should become a Major Secondary Endpoint in Clinical Practice and in Clinical Trials. PMID- 27664270 TI - Alternative splicing of basic chitinase gene PR3b in the low-nicotine mutants of Nicotiana tabacum L. cv. Burley 21. AB - Two unlinked semi-dominant loci, A (NIC1) and B (NIC2), control nicotine and related alkaloid biosynthesis in Burley tobaccos. Mutations in either or both loci (nic1 and nic2) lead to low nicotine phenotypes with altered environmental stress responses. Here we show that the transcripts derived from the pathogenesis related (PR) protein gene PR3b are alternatively spliced to a greater extent in the nic1 and nic2 mutants of Burley 21 tobacco and the nic1nic2 double mutant. The alternative splicing results in a deletion of 65 nucleotides and introduces a premature stop codon into the coding region of PR3b that leads to a significant reduction of PR3b specific chitinase activity. Assays of PR3b splicing in F2 individuals derived from crosses between nic1 and nic2 mutants and wild-type plants showed that the splicing phenotype is controlled by the NIC1 and NIC2 loci, even though NIC1 and NIC2 are unlinked loci. Moreover, the transcriptional analyses showed that the splicing patterns of PR3b in the low-nicotine mutants were differentially regulated by jasmonate (JA) and ethylene (ET). These data suggest that the NIC1 and NIC2 loci display differential roles in regulating the alternative splicing of PR3b in Burley 21. The findings in this study have provided valuable information for extending our understanding of the broader effects of the low-nicotine mutants of Burley 21 and the mechanism by which JA and ET signalling pathways post-transcriptionally regulate the activity of PR3b protein. PMID- 27664273 TI - Identification of Research Priorities for Inflammatory Bowel Disease Nursing in Europe: a Nurses-European Crohn's and Colitis Organisation Delphi Survey. AB - Background: Robust research evidence should inform clinical practice of inflammatory bowel disease [IBD] specialist nurses, but such research is currently very limited. With no current agreement on research priorities for IBD nursing, this survey aimed to establish topics to guide future IBD nursing research across Europe. Methods: An online modified Delphi survey with nurse and allied health professional members of the Nurses European Crohn's and Colitis Organisation [n = 303] was conducted. In Round One, participants proposed topics for research. In Round Two, research topics were rated on a 1-9 scale and subsequently synthesised to create composite research questions. In Round Three, participants selected their top five research questions, rating these on a 1-5 scale. Results: Representing 13 European countries, 88, 90 and 58 non-medical professionals, predominantly nurses, responded to Rounds One, Two and Three, respectively. In Round One, 173 potential research topics were suggested. In Rounds Two And Three, responders voted for and prioritised 125 and 44 questions, respectively. Round Three votes were weighted [rank of 1 = score of 5], reflecting rank order. The top five research priorities were: interventions to improve self-management of IBD; interventions for symptoms of frequency, urgency and incontinence; the role of the IBD nurse in improving patient outcomes and quality of life; interventions to improve IBD fatigue; and care pathways to optimise clinical outcomes and patient satisfaction. Conclusions: The prioritised list of topics gives clear direction for future IBD nursing research. Conducting this research has potential to improve clinical practice and patient-reported outcomes. PMID- 27664274 TI - Fluoxetine for Maintenance of Remission and to Improve Quality of Life in Patients with Crohn's Disease: a Pilot Randomized Placebo-Controlled Trial. AB - Background and Aims: Previous studies have shown that antidepressants reduce inflammation in animal models of colitis. The present trial aimed to examine whether fluoxetine added to standard therapy for Crohn's disease [CD] maintained remission, improved quality of life [QoL] and/or mental health in people with CD as compared to placebo. Methods: A parallel randomized double-blind placebo controlled trial was conducted. Participants with clinically established CD, with quiescent or only mild disease, were randomly assigned to receive either fluoxetine 20 mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and completed mental health and QoL questionnaires. Immune functions were assessed by stimulated cytokine secretion [CD3/CD28 stimulation] and flow cytometry for cell type. Linear mixed-effects models were used to compare groups. Results: Of the 26 participants, 14 were randomized to receive fluoxetine and 12 to placebo. Overall, 14 [54%] participants were male. The mean age was 37.4 [SD=13.2] years. Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn's Disease Activity Index [F(3, 27.5)=0.064, p=0.978] or faecal calprotectin [F(3, 32.5)=1.08, p=0.371], but did have modest effects on immune function. There was no effect of fluoxetine on physical, psychological, social or environmental QoL, anxiety or depressive symptoms as compared to placebo [all p>0.05]. Conclusions: In this small pilot clinical trial, fluoxetine was not superior to placebo in maintaining remission or improving QoL. [ID: ACTRN12612001067864.]. PMID- 27664276 TI - Role of diffusion-weighted MRI in the differential diagnosis of endometrioid and non-endometrioid cancer of the uterus. AB - Background Many publications have examined the relationship between apparent diffusion coefficient (ADC) values and tumor grade in endometrial cancer. Nevertheless, none were designed to evaluate according to the histopathological type of endometrioid and non-endometrioid tumors. Purpose To evaluate the role of diffusion-weighted imaging (DWI) in the differential diagnosis of endometrioid and non-endometrioid cancer of the uterus, by comparing them with contrast enhanced magnetic resonance imaging (MRI) findings. Material and Methods Institutional review board approval and informed consent were obtained. The MRI findings of 63 patients with endometrial cancer were retrospectively evaluated and divided into four groups: Grades I, II, and III endometrioid tumors, and non endometrioid tumors. ADC values, DWI quotients ( b = 1000 s/mm2), and post contrast signal intensities between lesions and the myometrium (b1000q-Cq values) were evaluated. The one-way-ANOVA, student's t-test, Kruskal-Wallis test, and receiver operating characteristic (ROC) analysis were used for statistical evaluation. Results Mean ADC values were 0.86 +/- 0.14 in Grade I, 0.80 +/- 0.7 in Grade II, 0.71 +/- 0.14 in Grade III for endometrioid tumors, and 0.70 +/- 0.12 in non-endometrioid tumors. There was a significant difference in ADC values between Grade I and Grade III ( P = 0.006), and non-endometrioid tumors ( P = 0.003). The difference was also significant between Grades I + II and Grade III ( P = 0.009), and non-endometrioid tumors ( P = 0.004). Besides, there was a significant difference between endometrioid and non-endometrioid tumors ( P = 0.022). However, when considering b1000q (F = 0.640, P = 0.593) and Cq (chi2 = 6.233; P = 0.101), no significant difference was detected among the groups. Conclusion The difference in ADC values between the endometrioid and non endometrioid tumors was statistically significant. However, the difference in DWI and contrast-enhancement findings were not statistically significant. Furthermore, the mean ADC values had an inverse relationship with tumor grade in the endometrioid cancer group. PMID- 27664275 TI - Accuracy of Faecal Calprotectin and Neutrophil Gelatinase B-associated Lipocalin in Evaluating Subclinical Inflammation in UlceRaTIVE Colitis-the ACERTIVE study. AB - Background and Aims: Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. Methods: This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. Results: Macroscopic lesions [i.e. endoscopic Mayo score >=1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150 250 MUg/g for faecal calprotectin and 12 MUg/g for neutrophil gelatinase B associated lipocalin were proposed. Conclusions: Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values. PMID- 27664277 TI - Pudendal nerve and branch neuropathy: magnetic resonance neurography evaluation. AB - Pudendal neuralgia is being increasingly recognized as a cause of chronic pelvic pain, which may be related to nerve injury or entrapment. Due to its complex anatomy and branching patterns, the pudendal nerve abnormalities are challenging to illustrate. High resolution 3 T magnetic resonance neurography is a promising technique for the evaluation of peripheral neuropathies. In this article, the authors discuss the normal pudendal nerve anatomy and its variations, technical considerations of pudendal nerve imaging, and highlight the normal and abnormal appearances of the pudendal nerve and its branches with illustrative case examples. PMID- 27664278 TI - Single focus on breast magnetic resonance imaging: diagnosis based on kinetic pattern and patient age. AB - Background Because of its small size, a focus in breast magnetic resonance imaging (MRI) must be evaluated on the basis of characteristics other than morphologic features. Patient-related factors including patient age, in conjunction with lesion-related factors, could be useful for decision-making. Purpose To assess the probability of malignant foci based on both lesion- and patient-related factors, and to propose a relevant decision-making method. Material and Methods Foci in our breast MRI database dating from April 2006 to June 2013 were retrospectively identified and analyzed. A Fisher's exact test or a Mann-Whitney U test were performed for univariate analyses, and factors that showed a significant association with outcome in the univariate analyses were subjected to multivariate analysis using a logistic regression model. A decision tree was then drawn using the significant predictors confirmed by multivariate analysis. Results In total, 184 foci (168 benign, 16 malignant) in 184 patients were analyzed in our study. The presence of a washout pattern and older age were found to be significant predictors of malignancy ( P < 0.0001; odds ratio [OR], 17.8; P = 0.021; OR, 1.1, respectively). The main decisive node on the decision tree was the presence of a washout pattern, followed by whether the patient's age was >63 years. Conclusion An enhancing focus showing a washout pattern, especially in older patients, may warrant immediate biopsy rather than short interval follow-up. PMID- 27664279 TI - JAK2 Disease-Risk Variants Are Gain of Function and JAK Signaling Threshold Determines Innate Receptor-Induced Proinflammatory Cytokine Secretion in Macrophages. AB - JAK2 genetic variants are associated with inflammatory bowel disease (IBD) and JAK inhibitors are being evaluated for therapy targeting immune-mediated diseases, including IBD. As JAK pathway-mediated cytokine regulation varies across cell types and stimulation conditions, we examined how JAK signaling and IBD-associated JAK2 variants regulate distinct acute and chronic microbial product exposure outcomes in human myeloid cells, consistent with the conditions of initial entry and ongoing intestinal tissue residence, respectively. Macrophages from controls and ulcerative colitis patients carrying the IBD-risk rs10758669 CC genotype showed increased JAK2 expression and nucleotide-binding oligomerization domain 2-induced JAK2 phosphorylation relative to AA carriers. Interestingly, the threshold of JAK2 expression and signaling determined pattern recognition receptor (PRR)-induced outcomes; whereas anti-inflammatory cytokines progressively decreased with lower JAK2 expression, proinflammatory cytokines switched from decreased to increased secretion below a certain JAK2 expression threshold. Low JAK2-expressing rs10758669 AA macrophages were above this threshold; consequently, both PRR-induced pro- and anti-inflammatory cytokines were decreased. However, relative to rs10758669 CC risk carriers, AA carrier macrophages switched to increased nucleotide-binding oligomerization domain 2 induced proinflammatory cytokines at lower therapeutically used JAK inhibitor doses. Importantly, JAK inhibitors increased proinflammatory cytokines secreted by peripheral macrophages following chronic PRR stimulation and by human intestinal myeloid cells following exposure to intestinal pathogens. Mechanistically, the decreased response to and secretion of autocrine/paracrine IL-10, IL-4, IL-22 and thymic stromal lymphopoietin regulated these JAK-dependent outcomes in myeloid cells. Taken together, the JAK signaling threshold determines whether PRR-induced pro- and anti-inflammatory cytokines are reciprocally regulated in myeloid cells; consideration of JAK2 genotype and targeting of specific cell types might improve JAK-targeted therapy in immune-mediated diseases. PMID- 27664280 TI - TAP-Dependent and -Independent Peptide Import into Dendritic Cell Phagosomes. AB - Cross-presentation of phagocytosed Ags by MHC class I (MHC-I) molecules is thought to involve transport of cytosolic peptides into dendritic cell phagosomes, mediated by TAP transporters recruited from the endoplasmic reticulum. However, because pure and tightly sealed phagosomes are difficult to obtain, direct evidence for peptide transport into phagosomes has remained limited. Moreover, the parameters determining peptide uptake by, and survival in, phagosomes remain little characterized. In this study, we monitored peptide import into phagosomes by flow cytometry using two types of fluorescent reporter peptides, one of which directly bound to intraphagosomal beads. We observed that a peptide with high TAP affinity is imported into phagosomes in a TAP- and ATP dependent manner, as expected. However, surprisingly, import of the OVA peptide SIINFEKL, a CD8+ T cell epitope frequently used to study cross-presentation, is ATP-dependent but substantially TAP-independent. The half-life of both reporter peptides is shortened by enhanced phagosome maturation triggered by TLR signaling. Conversely, formation of complexes with MHC-I molecules enhances peptide accumulation in phagosomes. Collectively, these results confirm that TAP can import peptides into phagosomes, but they suggest that some peptides, including the popular SIINFEKL, can enter phagosomes also via a second unknown energy-dependent mechanism. Therefore, the frequently reported TAP dependence of cross-presentation of phagocytosed OVA may principally reflect a requirement for recycling MHC-I molecules rather than SIINFEKL import into phagosomes via TAP. PMID- 27664281 TI - Dok-1 and Dok-2 Regulate the Formation of Memory CD8+ T Cells. AB - Diverse signals received by CD8+ T cells are integrated to achieve the required magnitude of cell expansion and the appropriate balance of effector/memory CD8+ T cell generation. Notably, the strength and nature of TCR signaling influence the differentiation and functional capacity of effector and memory CD8+ T cells. Dok 1 and Dok-2, the two members of the Dok family expressed in T cells, negatively regulate TCR signaling in vitro. However, the role of Dok proteins in modulating T cell function in vivo has not yet studied. We studied the function of Dok-1 and Dok-2 proteins in the regulation of the CD8+ T cell response to vaccinia virus infection. Comparison of responses to vaccinia virus expressing OVA peptide SIINFEKL by wild-type and Dok-1/2-/- CD8+ OT-I cells showed that the absence of Dok-1 and Dok-2 slightly reduced the magnitude of virus-specific effector CD8+ T cell expansion. This was not due to reduced proliferation or enhanced apoptosis of effector CD8+ T cells. Dok-1/2-deficient effector CD8+ T cells showed increased cell surface TCR expression following virus infection in vivo and increased expression of granzyme B and TNF upon stimulation with peptide Ag ex vivo. Finally, Dok-1/2-deficient effector CD8+ T had a severe defect in survival that resulted in impaired generation of memory CD8+ T cells. These results reveal the critical involvement of Dok-1 and Dok-2 in a negative-feedback loop that prevents overactivation of CD8+ T cells and promotes memory formation. PMID- 27664283 TI - Erratum for Kavanagh et al., A Perspective on How the United States Fell behind Northern Europe in the Battle against Methicillin-Resistant Staphylococcus aureus. PMID- 27664282 TI - Multidrug-Resistant Pseudomonas aeruginosa Infection in a Child with Cystic Fibrosis. AB - We describe a pediatric cystic fibrosis patient who developed a pulmonary exacerbation due to two multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. In addition to these MDR organisms, the case was further complicated by beta-lactam allergy. Despite the MDR phenotype, both isolates were susceptible to an antimicrobial combination. PMID- 27664286 TI - Great Advances in Retina: Past, Present, and Future. PMID- 27664285 TI - Electroacupuncture pretreatment induces rapid tolerance to bupivacaine cardiotoxicity in rats. AB - BACKGROUND: Evidence suggests that electroacupuncture (EA) protects against arrhythmia and myocardial injury induced by myocardial ischaemia-reperfusion. However, to our knowledge, it remains unknown whether EA could alleviate bupivacaine-induced cardiotoxicity. Therefore, we aimed to explore the effect of EA pretreatment on bupivacaine-induced cardiac arrest and outcomes of cardiopulmonary resuscitation (CPR) in rats. METHODS: 24 adult male Sprague Dawley rats were randomly divided into two groups: EA (n=12), and minimal acupuncture (MA) (n=12). Rats in both groups were needled at bilateral PC6, ST36, and ST40. Needles in the EA group were electrically stimulated for 60 min. ECG and invasive arterial blood pressure measurements were recorded. Two hours after EA or MA, 10 mg/kg bupivacaine was infused intravenously at a rate of 5 mg/kg/min in all rats. Rats suffering cardiac arrest were immediately subjected to CPR. At the end of the experiment, arterial blood samples were taken from surviving rats for blood gas analysis. RESULTS: The time from bupivacaine infusion until 20% prolongation of the QRS and QT interval, and the time to cardiac arrest, were notably increased among the rats pretreated with EA. Moreover, EA pretreatment significantly improved mean arterial pressure and heart rate at all monitored points after bupivacaine infusion. The proportion of animals surviving was higher in the EA group (9/12) than the MA group (3/12) at the end of experiment (p=0.039). CONCLUSIONS: Tolerance to bupivacaine-induced cardiotoxicity appeared to be increased following EA pre-treatment. The mechanism of action underlying the effects of EA on bupivacaine-induced cardiotoxicity requires further investigation. PMID- 27664287 TI - Stem Cell Treatment: Think Twice If They Ask for Payment. PMID- 27664288 TI - Historical Perspectives on the Management of Macular Degeneration, Diabetic Retinopathy, and Retinal Detachment: Personal Reminiscences. AB - We were challenged and delighted when Dr. Sharon Solomon, guest editor of this Retina Supplement, invited us to reminisce about caring for patients with common retinal disorders before there was access to the diagnostic and therapeutic tools that are readily available today. We agreed to confine our remarks to 3 common, but serious, conditions: age-related macular degeneration (Dr. Fine), diabetic retinopathy (Dr. Goldberg), and retinal detachment (Dr. Tasman). Each of us completed our ophthalmology training about half a century ago. At that time, a patient who received any 1 of the 3 diagnoses was at considerable risk of severe and irreversible loss of vision. Most readers today will have little if any experience in evaluating and treating such patients without access to a plethora of diagnostic and therapeutic technologies, including intravenous fluorescein angiography, laser photocoagulation, optical coherence tomography, ophthalmic ultrasound, angioinhibitory drugs, vitrectomy, intraocular gases, and many others. We are both pleased and privileged that each of us has practiced our profession long enough to enjoy what the enormous technological developments of the past half century, as described in this article, have meant for our patients. PMID- 27664289 TI - Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Retinal Disease: From Bench to Bedside. AB - The association of retinal hypoxia with retinal neovascularization has been recognized for decades, causing Michaelson to postulate in 1948 that a factor secreted by hypoxic retina was involved. The isolation of vascular endothelial growth factor (VEGF), characterization of its angiogenic activity, and demonstration that its expression was increased in hypoxic tissue made it a prime candidate. Intraocular levels of VEGF are elevated in patients with retinal or iris neovascularization, and VEGF-specific antagonists markedly suppress retinal neovascularization in mice and primates with ischemic retinopathy. Vascular endothelial growth factor antagonists also suppress choroidal neovascularization, and transgenic expression of VEGF in the retina of mice causes subretinal neovascularization. Clinical trials using a VEGF antagonist that blocks all isoforms of VEGF-A in patients with neovascular age-related macular degeneration (nAMD) demonstrated dramatic benefit. Similar results have been obtained with 2 other VEGF antagonists. Retinal hypoxia also contributes to diabetic macular edema (DME), and because of the absence of good animal models, small clinical trials were used to test the role of VEGF. The results clearly implicated VEGF as a major contributor to DME and have been confirmed by several large multicenter trials. A similar strategy demonstrated that VEGF is a major contributor to macular edema resulting from retinal vein occlusion, also confirmed in multicenter trials. Secondary outcomes in these large clinical trials have shown that VEGF inhibition improves retinal hemorrhages, retinal vessel closure, and progression of nonproliferative diabetic retinopathy. Anti-VEGF agents also provide therapeutic benefits in proliferative diabetic retinopathy. Thus, the development of VEGF antagonists has revolutionized the treatment of nAMD, diabetic retinopathy, and other ischemic retinopathies, but in many patients, the upregulation of VEGF is prolonged. Although the molecular signaling by which hypoxia and some other insults lead to upregulation of VEGF has been elucidated, it has not yet led to a treatment that reliably reduces the production of VEGF, necessitating continued neutralization by repeated intraocular injections of VEGF antagonists in many patients. The next horizon in the evolution of anti-VEGF therapy is the development of longer-acting agents or delivery platforms that provide sustained neutralization with fewer injections. PMID- 27664290 TI - The Bionic Eye: A Quarter Century of Retinal Prosthesis Research and Development. AB - This article describes the history of visual prostheses, with emphasis on the development of the Argus II retinal prosthesis system (Second Sight Medical Products, Inc., Sylmar, CA). A brief overview of cortical electrical stimulation in the blind is provided, followed by an account of the design and development of retinal stimulation equipment at the Duke Eye Center in the late 1980s; the first human intraoperative tests there and the subsequent 8 years of tests at the Wilmer Eye Institute; the transfer of the project to the Doheny Eye Institute at the University of Southern California and the founding of Second Sight Medical Products; and the development and clinical trials of the Argus I and Argus II systems. In a series of vignettes, we pay tribute to the many colleagues and patient volunteers without whose help the work would not have been possible. PMID- 27664291 TI - Gene Therapy and Stem Cell Transplantation in Retinal Disease: The New Frontier. AB - Gene and cell therapies have the potential to prevent, halt, or reverse diseases of the retina in patients with currently incurable blinding conditions. Over the past 2 decades, major advances in our understanding of the pathobiologic basis of retinal diseases, coupled with growth of gene transfer and cell transplantation biotechnologies, have created optimism that previously blinding retinal conditions may be treatable. It is now possible to deliver cloned genes safely and stably to specific retinal cell types in humans. Preliminary results testing gene augmentation strategies in human recessive diseases suggest promising safety and efficacy profiles, including improved visual function outcomes over extended periods. Additional gene-based strategies under development include approaches to autosomal dominant disease ("gain of function"), attempts to deliver genes encoding therapeutic proteins with proven mechanisms of action interfering with specific disease pathways, and approaches that could be used to render retinal cells other than atrophied photoreceptors light sensitive. In the programs that are the furthest along-pivotal regulatory safety and efficacy trials studying individuals with retinal degeneration resulting from RPE65 mutations-initial results reveal a robust safety profile and clinically significant improvements in visual function, thereby making this program a frontrunner for the first approved gene therapy product in the United States. Similar to gene therapy, progress in regenerative or stem cell-based transplantation strategies has been substantial. It is now possible to deliver safely stem cell-derived, terminally differentiated, biologically and genetically defined retinal pigment epithelium (RPE) to the diseased human eye. Although demonstration of clinical efficacy is still well behind the gene therapy field, multiple programs investigating regenerative strategies in RPE disease are beginning to enroll subjects, and initial results suggest possible signs of efficacy. Stem cells capable of becoming other retinal cell types, such as photoreceptors, are on the cusp of clinical trials. Stem cell-derived transplants can be delivered to precise target locations in the eye, and their ability to ameliorate, reverse, regenerate, or neuroprotect against disease processes can be assessed. Results from these studies will provide foundational knowledge that may lead to clinically significant therapies for currently untreatable retinal disease. PMID- 27664293 TI - Studying nuclear functions of aminoacyl tRNA synthetases. AB - Aminoacyl tRNA synthetases (AARSs) are best known for their essential role in translation in the cytoplasm. The concept that AARSs also exist in the nucleus started to draw attention around the turn of the new millennium, when aminoacylated tRNAs were first found in the nuclei of Xenopus oocytes. It is now expected that all cytoplasmic AARSs are present in the nucleus. In addition to tRNA aminoacylation, nuclear AARSs were found to regulate a spectrum of biological processes and responses, with many AARSs functioning through regulation at the level of gene transcription. In this paper, we focus on describing methods that have been successfully implemented to study AARSs in transcriptional regulation. These include a cell fractionation assay to detect nuclear localization, an in vitro DNA-cellulose pull-down assay to determine DNA binding capacity, and a chromatin immunoprecipitation (ChIP)-DNA deep sequencing assay to identify DNA binding sites. Application of these methods would expand our understanding of AARS functions and reveal critical insights on the coordination of gene transcription and translation. PMID- 27664294 TI - Multiple objects detection in biological images using a marked point process framework. AB - The marked point process framework has been successfully developed in the field of image analysis to detect a configuration of predefined objects. The goal of this paper is to show how it can be particularly applied to biological imagery. We present a simple model that shows how some of the challenges specific to biological data are well addressed by the methodology. We further describe an extension to this first model to address other challenges due, for example, to the shape variability in biological material. We finally show results that illustrate the MPP framework using the "simcep" algorithm for simulating populations of cells. PMID- 27664292 TI - Simultaneous detection of the subcellular localization of RNAs and proteins in cultured cells by combined multicolor RNA-FISH and IF. AB - Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) are sensitive techniques used for detecting nucleic acids and proteins in cultured cells. However, these techniques are rarely applied together, and standard protocols are not readily compatible for sequential application on the same specimen. Here, we provide a user-friendly step-by-step protocol to perform multicolor RNA-FISH in combination with IF to simultaneously detect the subcellular localization of distinct RNAs and proteins in cultured cells. We demonstrate the use of our protocol by analyzing changes in the subcellular distribution of RNAs and proteins in cells exposed to a variety of stress conditions. PMID- 27664295 TI - Chemerin processing in the myocardium: A mechanism in search of a function. PMID- 27664296 TI - No significant effect of transcranial direct current stimulation (tDCS) found on simple motor reaction time comparing 15 different simulation protocols. AB - BACKGROUND: Research exploring the behavioral impact of transcranial direct current stimulation (tDCS) over M1 has produced homogenous results. The most common explanations to address this homogeneity concerns the differential impact of varied tDCS parameters (such as stimulation intensity or electrode montage). To explore this, we systematically examined the effects of 15 different tDCS protocols on a well-elucidated neurobehavioral system: simple visual motor reaction time (smRT). METHODS: For the initial phase of this study, 150 healthy participants were randomly assigned to one of 5 experimental groups (2mA anodal, 2mA cathodal, 1mA anodal, 1mA cathodal, or sham) across 3 different conditions (orbitofrontal, bilateral, or extracephalic reference electrode location). The active electrode was always placed over M1 and tDCS lasted for 20min. Starting ~5min prior to stimulation and running continuously for ~30min, participants were repeatedly presented with a visual cue centered on a computer monitor and asked to press a response button as quickly as possible at stimulus onset (stimuli number: 100 pre-, 400 during-, and 100-post stimulation - interstimulus interval: 1-3s). Ex-gaussian distribution curves, miss, and error rates were determined for each normalized batch of 100 RTs and compared using a two-way ANOVA. As the largest group differences were seen with 2mA anodal (compared to sham) stimulation using an orbitofrontal montage, an additional 60 healthy participants were recruited to further test for significance in this condition. RESULTS: No significant impact of tDCS was seen on any parameter of smRT distribution, error rate, or miss rate, regardless of polarity, stimulation intensity, electrode montage, or stimulation-to-task relationship. CONCLUSION: Our results suggest that tDCS over M1 might not have a predictable or reliable effect on short duration smRT. Our results raise interesting questions regarding the mechanisms by which tDCS might modulate more complex motor behaviors. Additional research utilizing multiple tDCS protocols as undertaken here will help address and clarify these concerns. PMID- 27664297 TI - Influence of subthalamic deep-brain stimulation on cognitive action control in incentive context. AB - Subthalamic nucleus deep-brain stimulation (STN-DBS) is an effective treatment in Parkinson's disease (PD), but can have cognitive side effects, such as increasing the difficulty of producing appropriate responses when a habitual but inappropriate responses represent strong alternatives. STN-DBS also appears to modulate representations of incentives such as monetary rewards. Furthermore, conflict resolution can be modulated by incentive context. We therefore used a rewarded Simon Task to assess the influence of promised rewards on cognitive action control in 50 patients with PD, half of whom were being treated with STN DBS. Results were analyzed according to the activation-suppression model. We showed that STN-DBS (i) favored the expression of motor impulsivity, as measured with the Barratt Impulsiveness Scale, (ii) facilitated the expression of incentive actions as observed with a greater increase in speed according to promised reward in patients with versus without DBS and (iii) may increase impulsive action selection in an incentive context. In addition, analysis of subgroups of implanted patients suggested that those who exhibited the most impulsive action selection had the least severe disease. This may indicate that patients with less marked disease are more at risk of developing impulsivity postoperatively. Finally, in these patients, incentive context increased the difficulty of resolving conflict situations. As a whole, the current study revealed that in patients with PD, STN-DBS affects the cognitive processes involved in conflict resolution, reward processing and the influence of promised rewards on conflict resolution. PMID- 27664301 TI - ? PMID- 27664300 TI - Triclosan loaded electrospun nanofibers based on a cyclodextrin polymer and chitosan polyelectrolyte complex. AB - This work focuses on the relevance of antibacterial nanofibers based on a polyelectrolyte complex formed between positively charged chitosan (CHT) and an anionic hydroxypropyl betacyclodextrin (CD)-citric acid polymer (PCD) complexing triclosan (TCL). The study of PCD/TCL inclusion complex and its release in dynamic conditions, a cytocompatibility study, and finally the antibacterial activity assessment were studied. The fibers were obtained by electrospinning a solution containing chitosan mixed with PCD/TCL inclusion complex. CHT/TCL and CHT-CD/TCL were also prepared as control samples. The TCL loaded nanofibers were analyzed by Scanning Electron Microscopy (SEM), Fourier Transformed Infrared spectroscopy (FTIR) and X-Ray Diffraction (XRD). Nanofibers stability and swelling behavior in aqueous medium were pH and CHT:PCD weight ratio dependent. Such results confirmed that CHT and PCD interacted through ionic interactions, forming a polyelectrolyte complex. A high PCD content in addition to a thermal post treatment at 90 degrees C were necessary to reach a nanofibers stability during 15days in soft acidic conditions, at pH=5.5. In dynamic conditions (USP IV system), a prolonged release of TCL with a reduced burst effect was observed on CHT-PCD polyelectrolyte complex based fibers compared to CHT-CD nanofibers. These results were confirmed by a microbiology study showing prolonged antibacterial activity of the nanofibers against Escherichia coli and Staphylococcus aureus. Such results could be explained by the fact that the stability of the polyelectrolyte CHT-PCD complex in the nanofibers matrix prevented the diffusion of the PCD/triclosan inclusion complex in the supernatant, on the contrary of the similar system including cyclodextrin in its monomeric form. PMID- 27664298 TI - NMDAR dependent intracellular responses associated with cocaine conditioned place preference behavior. AB - The aim of this study was to investigate the intracellular responses associated with the acquisition and expression of cocaine-context associations. ERK (extracellular regulated kinase), CREB (cAMP responsive element binding protein), FosB and DeltaFosB proteins were of particular interest due to their involvement in cocaine reward and in synaptic plasticity underlying learning and memory. We used the conditioned place preference (CPP) paradigm, which employs a Pavlovian conditioning procedure to establish an association between a drug-paired environment and the drug's rewarding effects, to study the role of these signaling pathways in cocaine-context associations. N-methyl-D-aspartate receptor (NMDAR) antagonism prior to cocaine administration during conditioning blocked the acquisition of cocaine CPP and reduced Nucleus Accumbens (NAc) phosphorylated ERK (pERK) and phosphorylated CREB (pCREB) levels following the CPP test (drug free). We also show that cocaine-induced increases in Caudate Putamen (CPu) FosB and DeltaFosB levels are decreased after MK-801 pre-treatment during conditioning. In addition, our results provide evidence for the involvement of striatal SIRT (Silent Information Regulator of Transcription) proteins in cocaine CPP. These results will aid in the advancement of general knowledge about the molecular formation and retrieval of cocaine-associated memories that can be used in the future when designing treatments for cocaine addiction that target both prevention and relapse. PMID- 27664302 TI - ? PMID- 27664299 TI - Intermittent treatment with haloperidol or quetiapine does not disrupt motor and cognitive recovery after experimental brain trauma. AB - Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D2 receptor. The goal of this study was to test the hypotheses that intermittent HAL and QUE would not hinder recovery of cognitive and motor function following TBI and that daily QUE would also not impair functional recovery, which would be in contrast to HAL. Seventy anesthetized male rats received either a controlled cortical impact or sham injury and were then randomly assigned to TBI and sham groups receiving HAL (0.5mg/kg) or QUE (10mg/kg) intraperitoneally once per day or once every other day and compared to each other and vehicle (VEH) controls. Motor function was assessed by beam balance/walk tests on post-operative days 1-5 and cognitive function was evaluated with a Morris water maze task on days 14-19. No differences were revealed among the sham groups in any task, and hence the data were pooled. No overall differences were detected among the TBI groups, regardless of treatment or administration paradigm [p>0.05], but all were impaired vs. SHAM controls [p<0.05]. The SHAM controls also performed significantly better in the cognitive test vs. all TBI groups [p<0.05]. Moreover, the TBI+continuous HAL group performed worse than the TBI+continuous VEH, TBI+continuous QUE, and TBI+intermittent QUE groups [p<0.05], which did not differ from one another. Overall, the data suggest that QUE does not exacerbate TBI-induced cognitive and motor deficits, which supports the hypothesis. QUE may prove useful as an alternative APD treatment for management of agitation and aggression after clinical TBI. HAL may also be safe, but only if used sparingly. PMID- 27664303 TI - [Emergency medical aid in a paediatrics context]. AB - In France, the organisation of aid involves the intervention of the emergency medical services (Samu), which coordinate the medical regulation platforms for site 15 and the mobile emergency and intensive care services (Smur). Since they were created, the Samu have been tirelessly adapting their response to the various characteristics of pre-hospital assignments. Pre- and inter-hospital paediatrics has seen the development of specialised teams with the aim of providing effective aid which is adapted to the youngest and most vulnerable patients. PMID- 27664304 TI - [Paediatric mobile emergency and intensive care services, objectives and missions]. AB - The paediatric mobile emergency and intensive care service care teams have expertise in taking care of children in life-threatening circumstances. At the Robert-Debre Hospital in Paris, the paediatric Smur is multi-skilled, specialising particularly in transporting neonates and infants with severe cardiac or respiratory difficulties. The pathologies handled are very varied and include both neonatal pathologies and trauma pathologies in older children. PMID- 27664305 TI - [Teamwork in a paediatric mobile emergency and intensive care service]. AB - A paediatric mobile emergency and intensive care service team comprises several professionals with complementary skills. The cohesion of a team, as well as the listening and communication skills of each of its members, allow it to respond in the best possible way to emergency situations. Feedback sessions on practice and simulation exercises enhance teamwork. PMID- 27664306 TI - [Neonatal transport characteristics]. AB - Neonatal transport is necessary where a neonate is transferred between two care units. It provides all the skills of a dedicated team, representing a real mobile neonatal intensive care unit. Informing and involving the families is essential during this transport, which can be a source of stress for the child and its family. PMID- 27664307 TI - [The mobile paediatric circulatory support unit]. AB - A mobile paediatric circulatory support unit has been set up within the paediatric and neonatal intensive care service at the Armand-Trousseau Hospital in Paris (AP-HP, 75). It is in place for situations of refractory respiratory and/or circulatory failure and can intervene in a radius of several hundred kilometres, in order to establish long-term extracorporeal circulation. In this delicate context, transporting children requires specific skills, coordination between all intervening parties and faultless organisation. PMID- 27664308 TI - [Managing pain in paediatric Smur]. AB - The mobile emergency and intensive care service's handling of a child includes the assessment and treatment of pain. It is also essential to take anxiety into consideration. The relationship of trust established with the child and its family allows the stress and pain felt in emergency situations to be limited. PMID- 27664309 TI - [The mobile emergency and intensive care service, a place of transition for families]. AB - When the mobile emergency and intensive care service (Smur) intervenes with a child, the parents are in a completely unknown and anxiety-generating situation. The care team helps families to find their place, depending on the medical context and health status of the child. The intervention of the Smur therefore represents a place of transition for the parents. PMID- 27664310 TI - [Restraint in paediatric care]. AB - Restraint in general, and particularly when giving paediatric care, is a sensitive subject. This practice continues to appear often as a solution when children are disorientated or struggle during care. However, it is generally traumatic for the different care agents: the child, the parent and the care giver. Reflection on this subject has been carried out after exchanges with professionals about the use of restraint with children aged 2-4 during paediatric emergency care. PMID- 27664311 TI - [Nursing coordination for adolescents and young adults in oncology]. AB - The medical-psycho-socio-educational characteristics of adolescents and young adults affected by cancer require adapted management. Dedicated programmes and life spaces, as well as the availability of a mobile and transversal multidisciplinary team allow care to be customised. In this context, the coordinating nurse is an essential linchpin in the care team. PMID- 27664312 TI - Cognitive function and health literacy are independently associated with heart failure knowledge. AB - OBJECTIVES: Determine the relationship between cognitive function and health literacy in heart failure (HF) knowledge in patients with HF. BACKGROUND: HF requires extensive, complex treatment; thus, cognition and health literacy may contribute to understanding and self-management of HF. METHODS: Participants were 330 HF outpatients. Health literacy was assessed using the Medical Term Recognition Test and the Rapid Estimate of Adult Literacy in Medicine. Global cognitive function was screened with the Modified Mini-Mental Status Examination. HF knowledge was assessed with the Dutch Heart Failure Knowledge Scale (DHFKS). RESULTS: Health literacy (beta = .26, p < .001) and cognition (beta = .36, p < .001) were related to DHFKS. Both scores were independently associated with DHFKS (health literacy: beta = .13, p = .044 and cognition: beta = .30, p < .001). CONCLUSIONS: Impairments in health literacy and cognition were independently associated with reduced HF knowledge. Interventions should address both factors to be maximally effective. PMID- 27664314 TI - Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in mice. AB - Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and, in most cases, is of pro- or pre-B cell origin (B-ALL). The receptor tyrosine kinase KIT is expressed by hematopoietic stem and precursor cells. Gain-of function mutations of KIT cause systemic mastocytosis, which is characterized by abnormal accumulations of mast cells. We previously reported a mouse model of mastocytosis based on conditional expression of a constitutively active Kit protein. Half of these animals developed leukemic disease of B-lineage origin. Herein, we report that this condition bears striking similarities to human B-ALL. The immuno-phenotype of the leukemic cells was compatible with a pro-B-cell origin, as was the finding of immunoglobulin heavy-chain gene rearrangements in all cases, whereas light-chain loci were mostly not rearranged. Leukemogenesis was independent of pre-B-cell receptor expression. Primary leukemic cells and permanent cell lines derived from these were serially transplantable and rapidly killed the recipients. In a few animals, the leukemia was of T-cell origin with abnormal CD4/8 double-positive T-cell precursors dominating in the circulation. In summary, we report a novel ALL mouse model that may prove useful for in vivo drug testing and identification of novel oncogenic mutations and principles. PMID- 27664313 TI - Specific needs, concerns, strategies and advice of caregivers after coronary artery bypass surgery. AB - OBJECTIVE: To describe concerns, needs, strategies and advice of coronary artery bypass (CABG) caregivers during the first 3 months post-surgery. BACKGROUND: Nearly 400,000 patients underwent CABG surgery in 2010. While caregiving demand and difficulty has been investigated in early (4-8 weeks), mid (3 month), and later (6-12 months) recovery, no studies have explored early-to-mid concerns in depth. METHODS: In this qualitative study, a purposive sample of CABG partners participated in structured interviews. Themes for burden concerns, needs and strategies were derived using constant comparative analysis. RESULTS: One global theme 'knowing what I'm supposed to be doing' emerged. Specific themes related to medications, mobility, symptom monitoring, memory, appetite, emotional spirits, and finances. CONCLUSIONS: The resounding need for a dedicated caregiver program to prepare partners for their role, including what to expect, warrants exploration. Future research should validate these concerns in more diverse samples so interventions can be targeted to better support caregivers. PMID- 27664316 TI - A new fluorescence-based method for characterizing in vitro aerosol exposure systems. AB - Knowledge of how an in vitro aerosol exposure system delivers a test aerosols to the biological test system is among the most crucial prerequisites for the interpretation of exposure experiments and relies on detailed exposure system characterization. Although various methods for this purpose exist, many of them are time consuming, require extensive instrumentation, or offer only limited ability to assess the performance of the system under experimental settings. We present the development and evaluation of a new, highly robust and sensitive fluorometry-based method for assessing the particle size specific delivery of liquid aerosols. Glycerol aerosols of different mean particle sizes and narrow size distributions, carrying the fluorophore disodium fluorescein, were generated in a condensation monodisperse aerosol generator. Their detailed characterization confirmed their stability and the robustness and reproducibility of their generation. Test exposures under relevant experimental settings in the Vitrocell(r) 24/48 aerosol exposure system further confirmed their feasibility for simulating exposures and the high sensitivity of the method. Potential applications of the presented method range from the experimental confirmation of computationally simulated particle dynamics, over the characterization of in vitro aerosol exposure systems, to the detailed description of aerosol delivery in test systems of high complexity. PMID- 27664315 TI - A novel mechanism of functional cooperativity regulation by thiol redox status in a dimeric inorganic pyrophosphatase. AB - BACKGROUND: Inorganic PPases are essential metal-dependent enzymes that convert pyrophosphate into orthophosphate. This reaction is quite exergonic and provides a thermodynamic advantage for many ATP-driven biosynthetic reactions. We have previously demonstrated that cytosolic PPase from R. microplus embryos is an atypical Family I PPase. Here, we explored the functional role of the cysteine residues located at the homodimer interface, its redox sensitivity, as well as structural and kinetic parameters related to thiol redox status. METHODS: In this work, we used prokaryotic expression system for recombinant protein overexpression, biochemical approaches to assess kinetic parameters, ticks embryos and computational approaches to analyze and predict critical amino acids as well as physicochemical properties at the homodimer interface. RESULTS: Cysteine 339, located at the homodimer interface, was found to play an important role in stabilizing a functional cooperativity between the two catalytic sites, as indicated by kinetics and Hill coefficient analyses of the WT-rBmPPase. WT rBmPPase activity was up-regulated by physiological antioxidant molecules such as reduced glutathione and ascorbic acid. On the other hand, hydrogen peroxide at physiological concentrations decreased the affinity of WT-rBmPPase for its substrate (PPi), probably by inducing disulfide bridge formation. CONCLUSIONS: Our results provide a new angle in understanding redox control by disulfide bonds formation in enzymes from hematophagous arthropods. The reversibility of the down regulation is dependent on hydrophobic interactions at the dimer interface. GENERAL SIGNIFICANCE: This study is the first report on a soluble PPase where dimeric cooperativity is regulated by a redox mechanism, according to cysteine redox status. PMID- 27664317 TI - The unusual redox properties of C-type oxidases. AB - Cytochrome cbb3 (also known as C-type) oxidases belong to the family of heme copper terminal oxidases which couple at the end of the respiratory chain the reduction of molecular oxygen into water and the pumping of protons across the membrane. They are expressed most often at low pressure of O2 and they exhibit a low homology of sequence with the cytochrome aa3 (A-type) oxidases found in mitochondria. Their binuclear active site comprises a high-spin heme b3 associated with a CuB center. The protein also contains one low-spin heme b and 3 hemes c. We address here the redox properties of cbb3 oxidases from three organisms, Rhodobacter sphaeroides, Vibrio cholerae and Pseudomonas stutzeri by means of electrochemical and spectroscopic techniques. We show that the redox potential of the heme b3 exhibits a relatively low midpoint potential, as in related cytochrome c-dependent nitric oxide reductases. Potential implications for the coupled electron transfer and proton uptake mechanism of C-type oxidases are discussed. PMID- 27664318 TI - Methyl isobutyl ketone-induced hepatocellular carcinogenesis in B6C3F1 mice: A constitutive androstane receptor (CAR)-mediated mode of action. AB - In a National Toxicology Program (NTP) chronic inhalation study with methyl isobutyl ketone (MIBK), increases in hepatocellular adenomas and hepatocellular adenomas and carcinomas (combined) were observed in male and female B6C3F1 mice at 1800 ppm. A DNA reactive Mode-of-Action (MOA) for this liver tumor response is not supported by the evidence as MIBK and its major metabolites lack genotoxicity in both in vitro and in vivo studies. Constitutive androstane receptor (CAR) nuclear receptor-mediated activation has been hypothesized as the MOA for MIBK induced mouse liver tumorigenesis. To further investigate the MOA for MIBK induced murine liver tumors, male and female B6C3F1, C57BL/6, and CAR/PXR Knockout (KO) mice were exposed to either 0 or 1800 ppm MIBK for 6 h/day, 5 days/week for a total of 10 days. On day 1, mice were implanted with osmotic mini pumps containing 5-Bromo-2-deoxyuridine (BrdU) 1 h following exposure and humanely euthanized 1-3 h following the final exposure. B6C3F1 and C57BL/6 mice had statistically significant increases in liver weights compared to controls that corresponded with hepatocellular hypertrophy and increased mitotic figures. Hepatocellular proliferation data indicated induction of S-phase DNA synthesis in B6C3F1 and C57BL/6 mice exposed to 1800 ppm MIBK compared to control, and no increase was observed in MIBK exposed CAR/PXR KO mice. Liver gene expression changes indicated a maximally-induced Cyp2b10 (CAR-associated) transcript and a slight increase in Cyp3a11(PXR-associated) transcript in B6C3F1 and C57BL/6 mice exposed to 1800 ppm MIBK compared to controls, but not in Cyp1a1 (AhR-associated) or Cyp4a10 (PPAR-alpha-associated) transcripts. CAR/PXR KO mice exposed to 1800 ppm MIBK showed no evidence of activation of AhR, CAR, PXR or PPAR-alpha nuclear receptors via their associated transcripts. MIBK induced hepatic effects are consistent with a phenobarbital-like MOA where the initiating events are activation of the CAR and PXR nuclear receptors and resultant hepatocellular proliferation leading to rodent liver tumors. PMID- 27664320 TI - The effect of time changes in diagnosing lung cancer type on its recorded distribution, with particular reference to adenocarcinoma. AB - Among lung cancers, a substantial shift over time has occurred in the recorded frequency of adenocarcinoma (AdC) relative to that of squamous cell carcinoma (SqCC). This is evident in many countries, and also in those who have never smoked. We attempted to address the extent to which this increase is real, or an artefact of changing diagnostic practices. We reviewed studies re-evaluating diagnoses using more up-to-date criteria, and studies applying standard criteria to cases collected over a long period. We also describe changes to classifications, and factors affecting diagnostic accuracy and consistency. While the four main types have long remained essentially unchanged, successive WHO classifications differ in how tumours are ascribed to these types. Despite refinement of classifications and technological advances, the decision is ultimately the pathologist's. In 11 studies, 189/1212(15.6%) originally diagnosed AdCs were reclassified as non-AdC on review, whereas 541/1564(34.6%) of non-AdCs were reclassified as AdC, increasing AdCs by 30%. Studies examining trends in the proportion of AdC were conflicting; three showing a declining trend, seven no trend, and six some increase. Some studies find lepidic (bronchioloalveolar) carcinoma, but not other AdC sub-types, increased. The rising AdC/SqCC ratio results at least partly from diagnostic changes. PMID- 27664319 TI - Arsenic trioxide mediates HAPI microglia inflammatory response and the secretion of inflammatory cytokine IL-6 via Akt/NF-kappaB signaling pathway. AB - Arsenic is a widely distributed toxic metalloid in around the world. Inorganic arsenic species are deemed to affect astrocytes functions and to cause neuron apoptosis. Microglia are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA and reverse transcriptase PCR (RT-PCR), we showed that Arsenic trioxide up-regulated the expression and secretion of IL-6 in a dose dependent manner and a time-dependent manner in cultured HAPI microglia cells. These pro-inflammatory responses were inhibited by the Akt blocker, LY294002. Further, Arsenic trioxide exposure could induce phospho rylationand degradation of IkBalpha, and the translocation of NF-kappaB p65 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the NF-kB signaling pathway can be activated after Arsenic trioxide treatment. Besides, Akt blocker LY294002 also obviously attenuated NF-kB activation and transnuclear induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of pro inflammatory cytokine and NF-kB activation induced by Arsenic trioxide can be mediated by elevation of p-Akt in HAPI microglia cells. PMID- 27664321 TI - Polymeric nanocapsules as a technological alternative to reduce the toxicity caused by meloxicam in mice. AB - This study determined whether meloxicam in nanocapsules modifies stomach and liver damage caused by free meloxicam in mice. Male Swiss mice were treated with blank nanocapsules or meloxicam in nanocapsules or free meloxicam (10 mg/kg, intragastrically, daily for five days). On the seventh day, blood was collected to determine biochemical markers (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, total bilirubin, unconjugated bilirubin, albumin and alkaline phosphatase). Stomachs and livers were removed for histological analysis. There was no significant difference in the biochemical markers in the plasma of mice. Meloxicam in nanocapsules did not have an ulcerogenic potential in the stomach or cause lipid peroxidation in the stomach and liver. Free meloxicam increased the ulcerogenic potential in the stomach and lipid peroxidation in the stomach and liver. Meloxicam in nanocapsules caused less histological changes than free meloxicam. In conclusion, polymeric nanocapsules can represent a technological alternative to reduce the toxicity caused by meloxicam. PMID- 27664322 TI - Testing in artificial sweat - Is less more? Comparison of metal release in two different artificial sweat solutions. AB - Metal release from materials immersed in artificial sweat can function as a measure of potential skin exposure. Several artificial sweat models exist that, to various degree, mimic realistic conditions. Study objective was to evaluate metal release from previously examined and well characterized materials in two different artificial sweat solutions; a comprehensive sweat model intended for use within research, based on the composition of human sweat; and the artificial sweat, EN1811, intended for testing compliance with the nickel restriction in REACH. The aim was to better understand whether there are advantages using either of the sweat solutions in bio-elution testing of materials. Metal release in two different artificial sweat solutions was compared for discs of a white gold alloy and two hard metals, and a rock drilling insert of tungsten carbide at 1 h, 24 h, 1 week and 1 month. The released amount of metal was analysed by means of inductively coupled plasma mass spectrometry. Similar levels of released metals were measured from test materials in the two different artificial sweat solutions. For purposes in relation to legislations, it was concluded that a metal release test using a simple artificial sweat composition may provide results that sufficiently indicate the degree of metal release at skin contact. PMID- 27664323 TI - Subacute toxicity evaluation of KR-33493, FAF1 inhibitor for a new anti parkinson's disease agent, after oral administration in rats and dogs. AB - KR33493, a newly developed FAS-associated factor 1 (FAF1) inhibitor for Parkinson's disease, is being evaluated in a Phase I clinical trial. In the present study, the subchronic toxicity of KR33493 in Sprague-Dawley (SD) rats and beagle dogs was investigated at various oral doses for 28 and 14 days, respectively. During the study, food consumption, body weights, organ weights, gross findings, and mortality were examined; and ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, histopathology, and toxicokinetics were performed. In rats, weight gain decreased in both sexes at 500 mg/kg/day, with no significant differences. In dogs, some significant differences compared with the control were found during the trial; however, at the end of recovery periods, these were no longer observed and there was no dose correlation. Some histopathological findings were observed, but these were considered as incidental changes. Since no other significant changes were observed, doses above 500 and 1000 mg/kg KR33493 in rat and dogs, respectively, caused no observed adverse effects. Therefore, based on these results, the Phase 1 clinical trial for KR33493 was approved by the Korean Food & Drug Administration. PMID- 27664324 TI - Critical elements for human health risk assessment of less than lifetime exposures. AB - Less than lifetime exposure has confronted risk assessors as to how to interpret the risks for human health in case a chronic health-based limit is exceeded. Intermittent, fluctuating and peak exposures do not match with the basis of the chronic limit values possibly leading to conservative outcomes. This paper presents guidance on how to deal with human risk assessment of less than lifetime exposure. Important steps to be considered are characterization of the human exposure situation, evaluation whether the human less than lifetime exposure scenario corresponds to a non-chronic internal exposure: toxicokinetic and toxicodynamic considerations, and, finally, re-evaluation of the risk assessment. Critical elements for these steps are the mode of action, Haber's rule, and toxicokinetics (ADME) amongst others. Previous work for the endpoints non genotoxic carcinogenicity and developmental toxicity is included in the guidance. The guidance provides a way to consider the critical elements, without setting default factors to correct for the less than lifetime exposure in risk assessment. PMID- 27664326 TI - Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell Replete Allogeneic Hematopoietic Stem Cell Transplantation. AB - Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013. In multivariate analysis NK cell numbers on day 30 (NK30) > 150 cells/uL were independently associated with superior overall survival (hazard ratio, .79; 95% confidence interval, .66 to .95; P = .01). Cumulative incidence analyses showed that patients with NK30 > 150 cells/uL had significantly less transplant-related mortality (TRM), P = .01. Patients with NK30 > 150 cells/uL experienced significantly lower numbers of life-threatening bacterial infections as well as viral infections, including cytomegalovirus. No association was observed in relation to relapse. These results suggest an independent protective effect of high early NK cell reconstitution on TRM that translates into improved overall survival after T cell-replete HSCT. PMID- 27664325 TI - A Prospective Study of Alemtuzumab as a Second-Line Agent for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation. AB - We describe a single-center prospective study of alemtuzumab as a second-line agent for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in pediatric and young adult allogeneic hematopoietic stem cell transplant recipients. Alemtuzumab was administered for grades II to IV aGVHD if patients did not improve within 5 days or worsened within 48 hours after corticosteroids. Interim analyses of alemtuzumab levels and response were performed after every 5 patients enrolled, resulting in 3 dosing cohorts, as follows: (1) .2 mg/kg alemtuzumab subcutaneously on days 1 to 5 (maximum of 31 mg over 5 days) and .2 mg/kg/dose (not exceeding 10 mg/dose) on days 15, 22, and 29; (2) .2 mg/kg alemtuzumab subcutaneously on days 1 to 5 (maximum of 43 mg over 5 days) and .2 mg/kg/dose on day 7, 10, 15, 22, and 29; and (3) .2 mg/kg subcutaneously on days 1 to 5 and .2 mg/kg/dose on day 7, 10, 15, and 22. Alemtuzumab levels were assessed before starting alemtuzumab and at days 1, 3, 6, 10, and 14 and weekly until day 99, where day 1 was the day of first alemtuzumab dose. Fifteen patients (median age, 10 years; range, 1.4 to 27) received alemtuzumab for grades II (6%), III (74%), and IV (20%) SR-aGVHD. The overall response rate was 67%, with complete response (CR) in 40%, partial response (PR) in 27%, and no response in 33%. The median day 6 alemtuzumab level was 2.79 ug/mL (interquartile range, 1.34 to 4.89) in patients with CR compared with .62 ug/mL (interquartile range, .25 to 1.45) in patients with PR + no response (P < .05). Ninety percent (n = 9) of patients with a CR or PR reduced corticosteroid doses within 8 weeks from first alemtuzumab dose. Side effects included fever (26%) and transient thrombocytopenia (53%). Asymptomatic viremias occurred in all patients but invasive viral disease occurred in 2 patients. One patient developed Epstein-Barr virus-post-transplantation lymphoproliferative disorder. Eighty percent (n = 12) of patients were alive at 6 months, of whom 53% (n = 8) were free of GVHD whereas 13% (n = 2) developed chronic GVHD. Alemtuzumab is an effective second-line agent for children and young adults with SR-aGVHD. Higher alemtuzumab levels are associated with CR. A real-time dose adjusted alemtuzumab study is needed to further optimize the dose of alemtuzumab in aGVHD. PMID- 27664327 TI - Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. AB - Combining two or more antiretroviral drugs in one medical product is an interesting but challenging strategy for developing topical anti-HIV microbicides. We developed a new vaginal delivery system comprising the incorporation of nanoparticles (NPs) into a polymeric film base - NPs-in-film - and tested its ability to deliver tenofovir (TFV) and efavirenz (EFV). EFV-loaded poly(lactic-co-glycolic acid) NPs were incorporated alongside free TFV into fast dissolving films during film manufacturing. The delivery system was characterized for physicochemical properties, as well as genital distribution, local and systemic 24h pharmacokinetics (PK), and safety upon intravaginal administration to mice. NPs-in-film presented suitable technological, mechanical and cytotoxicity features for vaginal use. Retention of NPs in vivo was enhanced both in vaginal lavages and tissue when associated to film. PK data evidenced that vaginal drug levels rapidly decreased after administration but NPs-in-film were still able to enhance drug concentrations of EFV. Obtained values for area-under the-curve for EFV were around one log10 higher than those for the free drugs in aqueous vehicle (phosphate buffered saline). Film alone also contributed to higher and more prolonged local drug levels as compared to the administration of TFV and EFV in aqueous vehicle. Systemic exposure to both drugs was low. NPs-in film was found to be safe upon once daily vaginal administration to mice, with no significant genital histological changes or major alterations in cytokine/chemokine profiles being observed. Overall, the proposed NPs-in-film system seems to be an interesting delivery platform for developing combination vaginal anti-HIV microbicides. PMID- 27664329 TI - Optimization of in vivo DNA delivery with NickFect peptide vectors. AB - As the field of gene therapy progresses, an increasingly urgent need has arisen for efficient and non-toxic vectors for the in vivo delivery of nucleic acids. Cell-penetrating peptides (CPP) are very efficient transfection reagents in vitro, however, their application in vivo needs improvement. To enhance in vivo transfection we designed various CPPs based on previous knowledge of internalization studies and physiochemical properties of NickFect (NF) nanoparticles. We show that increment of the helicity of these Transportan10 analogues improves the transfection efficiency. We rationally design by modifying the net charge and the helicity of the CPP a novel amphipathic alpha-helical peptide NF55 for in vivo application. NF55 condenses DNA into stable nanoparticles that are resistant to protease degradation, promotes endosomal escape, and transfects the majority of cells in a large cell population. We demonstrate that NF55 mediates DNA delivery in vivo with gene induction efficiency that is comparable to commercial transfection reagents. In addition to gene induction in healthy mice, NF55/DNA nanoparticles showed promising tumor transfection in various mouse tumor models, including an intracranial glioblastoma model. The efficiency of NF55 to convey DNA specifically into tumor tissue increased even further after coupling a PEG2000 to the peptide via a disulphide-bond. Furthermore, a solid formulation of NF55/DNA displayed an excellent stability profile without additives or special storage conditions. Together, its high transfection efficacy and stability profile make NF55 an excellent vector for the delivery of DNA in vivo. PMID- 27664331 TI - Extracellular vesicles in food: Experimental evidence of their secretion in grape fruits. AB - In the last decade, the number of studies related with extracellular vesicles (EVs) has dramatically grown since their role as key part of intercellular communication has been confirmed. EVs, as transporter of distinct bioactive molecules, can take part in different physiological mechanisms and have been gaining attention as potential tools with a wide range of therapeutic effects. Whereas a high number of studies have been published related to mammalian derived EVs, including products as food source, the existence of EVs in plants still is controversial. Recent descriptions of vesicles derived from edible plants show that they might contain pharmacological active molecules. In this context, EVs from food are attracting increasing interest due to their relevance in modulating cellular processes (involved in health and disease), as well as therapeutic vehicles. The present work aims to summarize the current knowledge on exosomes in foods, actually limited to only four FAO groups (Milk, Starchy roots and tubers, Nuts and seeds, and Fruits). In addition, we have further characterized EVs isolated from grape berry juice by classical differential centrifugation, and described a preliminary dissection of their secretion in vivo. PMID- 27664330 TI - Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to immunoassay-based validation. AB - Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumor-specific molecules can be found in exosomes isolated from biological fluids. We have previously analyzed the proteome of urinary exosomes by mass spectrometry, and identified proteins differentially expressed in prostate cancer patients compared to healthy males. Since mass spectrometry is so far not commonly used in clinical laboratories, we have here investigated whether antibody-based methods such as Western blot or ELISA can be used to validate the use of the identified proteins as prostate cancer biomarkers. Western blot experiments designed to detect flotillin 2, TMEM256, Rab3B and LAMTOR1 showed that the level of these proteins was higher in urinary exosomes from prostate cancer patients compared to healthy males. Furthermore, a receiver operating characteristic curve of flotillin 2 in samples from 16 controls and 16 patients showed an area under the curve of 0.91, and 88% sensitivity at a threshold set to give 94% specificity. In addition, ELISA-based detection of flotillin 2 and PARK7 showed that the combination of these proteins was able to distinguish prostate cancer patients and healthy controls with 68% sensitivity and 93% specificity. Several promising biomarkers identified by mass spectrometry could not be evaluated by Western blot or ELISA due to their low exosomal amount and/or lack of good antibodies. In conclusion, our results show that several urinary exosomal proteins identified as prostate cancer biomarkers by mass spectrometry have a high diagnostic value also when analyzed by immunology-based methods, thus bringing these biomarkers closer to a potential clinical use. PMID- 27664328 TI - In vitro potency, in vitro and in vivo efficacy of liposomal alendronate in combination with gammadelta T cell immunotherapy in mice. AB - Nitrogen-containing bisphosphonates (N-BP), including zoledronic acid (ZOL) and alendronate (ALD), have been proposed as sensitisers in gammadelta T cell immunotherapy in pre-clinical and clinical studies. Therapeutic efficacy of N-BPs is hampered by their rapid renal excretion and high affinity for bone. Liposomal formulations of N-BP have been proposed to improve accumulation in solid tumours. Liposomal ALD (L-ALD) has been suggested as a suitable alternative to liposomal ZOL (L-ZOL), due to unexpected mice death experienced in pre-clinical studies with the latter. Only one study so far has proven the therapeutic efficacy of L ALD, in combination with gammadelta T cell immunotherapy, after intraperitoneal administration of gammadelta T cell resulting in delayed growth of ovarian cancer in mice. This study aims to assess the in vitro efficacy of L-ALD, in combination with gammadelta T cell immunotherapy, in a range of cancerous cell lines, using L ZOL as a comparator. The therapeutic efficacy was tested in a pseudo-metastatic lung mouse model, following intravenous injection of gammadelta T cell, L-ALD or the combination. In vivo biocompatibility and organ biodistribution studies of L N-BPs were undertaken simultaneously. Higher concentrations of L-ALD (40-60MUM) than L-ZOL (3-10MUM) were required to produce a comparative reduction in cell viability in vitro, when used in combination with gammadelta T cells. Significant inhibition of tumour growth was observed after treatment with both L-ALD and gammadelta T cells in pseudo-metastatic lung melanoma tumour-bearing mice after tail vein injection of both treatments, suggesting that therapeutically relevant concentrations of L-ALD and gammadelta T cell could be achieved in the tumour sites, resulting in significant delay in tumour growth. PMID- 27664332 TI - Nasal drug absorption from powder formulations: The effect of three types of hydroxypropyl cellulose (HPC). AB - Despite the numerous advantages of powder formulations, few studies have described their nasal drug absorption. The first aim of this study was to compare the drug absorption from powder formulation with that from a liquid formulation in rats. Since pharmaceutical excipients are usually added to most powder formulations, the second aim of the study was to investigate the effect of hydroxypropyl cellulose (HPC) on nasal drug absorption from the powder. Three types of HPC with different polymerization degrees were used: HPC(SL), HPC(M), and HPC(H). The model drugs were warfarin (BCS Class I), piroxicam (BCS Class II), and sumatriptan (BCS Class III). The absorption of these model drugs in the powder form was higher than that from the solution. All HPCs failed to enhance warfarin absorption, while the piroxicam absorption was enhanced only by HPC(M). Sumatriptan absorption was not enhanced by HPC(SL), but by HPC(M) and HPC(H). The differences in nasal absorption of the three model drugs promoted by HPCs depend on the permeability and solubility of the drug. Moreover, the nasal retention of different formulations was increased by HPCs. Because HPCs showed no toxic effect on the nasal epithelium. These findings indicate that powder formulations supplemented with HPC are a valuable and promising approach to increase the nasal absorption of highly soluble and poorly permeable drugs. PMID- 27664333 TI - Large-scale study of herd-level risk factors for bovine brucellosis in Brazil. AB - Bovine brucellosis is an important zoonosis caused by Brucella abortus that negatively impacts livestock productivity. In 2001, Brazil launched a new national program aimed at eradicating animal brucellosis that included large scale studies of the prevalence and risk factors to support strategic decision making. These studies were implemented by the animal health authorities and were underpinned by the scientific coordination of the University of Sao Paulo and the University of Brasilia. The state-level results were published and revealed important differences in herd prevalence among regions. The risk factors varied across states and did not clearly explain the observed spatial disease spread. This study used a consolidated herd-level database of 14 states and 17,100 herds, from the prevalence surveys' data, to gain insights into herd profiles and cattle production practices that might be associated with the risk of brucellosis. At the time of data collection, the study area comprised just over 56 million bovine females aged over 24 months and approximately 1.8 million herds. After an exploratory univariable analysis, all factors with p<=0.20 were included in a multiple logistic regression model, using the design-based method in order to take herd sampling weights into account. The number of females in the herd markedly increased the risk of infection; compared with smaller herds (less than 30 females), the odds ratio was 3.42 [CI 95% 2.98-3.91] for herds with 31 to 100 females, 5.68 [4.92-6.55] for herds with 101 to 400 females, and 13.14 [10.94 15.78] for herds with more than 400 females. The risk was higher for extensive cattle production farms (OR=1.23 [1.07-1.42]) and for farms that purchased replacement stock from cattle traders (OR=1.27 [1.08-1.47]) or directly from other farms (OR=1.19 [1.07-1.32]). The exclusive use of artificial insemination (OR=0.57 [0.4-0.81]) and regular veterinary support (OR=0.68 [0.6-0.77]) appeared to be protective factors. These findings are consistent with the regional prevalence trends observed in the study and provide key guidance for the planning of the national effort to control and eradicate brucellosis. High vaccination coverage of heifers is recommended, especially when targeted to areas where large scale extensive cattle production predominates. The smaller, more intensive herds, are good candidates for disease accreditation schemes. PMID- 27664334 TI - Molecular typing of isolates obtained from aborted foetuses in Brucella-free Holstein dairy cattle herd after immunisation with Brucella abortus RB51 vaccine in Egypt. AB - Bovine brucellosis is endemic in Egypt in spite of application of surveillance and control measures. An increase of abortions was reported in a Holstein dairy cattle herd with 600 animals in Damietta governorate in Egypt after immunisation with Brucella (B.) abortus RB51 vaccine. Twenty one (10.6%) of 197 vaccinated cows aborted after 3 months. All aborted cows had been tested seronegative for brucellosis in the past 3 years. B. abortus was isolated from four foetuses. Conventional biochemical and bacteriological identification and polymerase chain reaction (PCR) confirmed two B. abortus biovar (bv.) 1 smooth and two B. abortus rough strains. None of the B. abortus isolates were identified as RB51. Genotyping analysis by multiple locus of variable number tandem repeats analysis based on 16 markers (MLVA-16) revealed two different profiles with low genetic diversity. B. abortus bv1 was introduced in the herd and caused abortions. PMID- 27664335 TI - Erroneous HbA1c results in a patient with elevated HbC and HbF. AB - BACKGROUND: HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. METHODS: HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. RESULTS: HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. CONCLUSION: Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM. PMID- 27664336 TI - UPLC-MS/MS determination of florfenicol and florfenicol amine antimicrobial residues in tilapia muscle. AB - Despite the benefits to fish farmers, the use of antimicrobials in aquaculture has concerned consumers and competent authorities. The indiscriminate use of such substances promotes the emergence of resistant microorganisms, decreases the effectiveness of treatments, and causes possible toxic effects in humans. In Brazil, florfenicol is the only antimicrobial registered for use in aquaculture and is often used in tilapia in cage creation. Thus, this study aimed to develop a method for determination of florfenicol residues and its metabolite florfenicol amine in tilapia fillet by UPLC-MS/MS. Analytes were extracted with ethyl acetate, followed by liquid-liquid partition clean-up with hexane and SPE. The sorbents C18, phenyl and HLB-Oasis were evaluated by SPE. Phenyl sorbent showed the best results, and the extraction conditions were optimized in the sample matrix with fractional factorial design 24-1. The analytes were separated on a C18 chromatographic column (50*2.1mm*1.7MUm) using water (A) and acetonitrile (B) as mobile phase at a flow rate of 0.3mLmin-1 with a linear gradient (in% B): 0 2.0min: 20%; 2.0-2.5min: increase to 90%; 2.5-3.5min: 90%; 3.0-3.5min: decrease to 20%; 4.0-5.0min: 20%. The analytes were monitored in a MS/MS triple quadrupole system by MRM mode with transitions at m/z 356.1>336.1 (florfenicol) and m/z 248.1>130.1 (florfenicol amine). The optimized method was validated obtaining LOQ values of 3 and 25ngg-1 for florfenicol and florfenicol amine, respectively, precision between 20 and 36%, absolute extraction efficiency between 38 and 80%, and adequate linearity. The method was applied to samples intended for human consumption, and within the 15 evaluated samples, only one showed florfenicol residue at 30ngg-1, which is below the maximum residue limit established in Brazil. PMID- 27664337 TI - Patient knowledge regarding radiation exposure from spinal imaging. AB - BACKGROUND CONTEXT: Spine surgeons employ a high volume of imaging in the diagnosis and evaluation of spinal pathology. However, little is known regarding patients' knowledge of the radiation exposure associated with these imaging techniques. PURPOSE: To characterize spine patients' knowledge regarding radiation exposure from various imaging modalities. STUDY DESIGN/SETTING: A cross sectional survey study. PATIENT SAMPLE: One hundred patients at their first clinic visit with a single spine surgeon at an urban institution. OUTCOME MEASURES: The primary outcome was patient estimate of radiation dose for various common spinal imaging modalities as compared with true dose. METHODS: An electronic survey was administered to all new patients before their first appointment with a single spinal surgeon. The survey asked patients to estimate how many chest x-rays (CXRs) worth of radiation were equivalent to various common spinal imaging modalities. Patient estimates were compared to true effective radiation doses determined from the literature. The survey also asked patients whether they would consider avoiding types of imaging modalities out of concern for excessive radiation exposure. RESULTS: Patients accurately approximated the radiation associated with two views of the cervical spine, with a median estimate of 3.5 CXRs, compared with an actual value of 4.7 CXRs. However, patients underestimated the dose for computed tomography (CT) scans of the cervical spine (2.0 CXRs vs. 145.3 CXRs), two views of the lumbar spine (3.0 CXRs vs. 123.3 CXRs), and CT scans of the lumbar spine (2.0 CXRs vs. 638.3 CXRs). The majority of patients believed that there is at least some radiation exposure associated with magnetic resonance imaging (MRI). The percent of patients who would consider forgoing imaging recommend by their surgeon out of concern for radiation exposure was 14% for x-rays, 13% for CT scans, and 9% for MRI. CONCLUSION: These results demonstrate a lack of patient understanding regarding radiation exposure associated with common spinal imaging techniques. These data suggest that patients might benefit from increased counseling and/or educational materials regarding radiation exposure before undergoing diagnostic imaging of the cervical or lumbar spine. PMID- 27664338 TI - An unusual cause of cervical kyphosis. AB - BACKGROUND CONTEXT: Acute fixed cervical kyphosis may be a rare presentation of conversion disorder, psychogenic dystonia, and potentially as a side effect from typical antipsychotic drugs. Haldol has been associated with acute dystonic reactions. In some cases, rigid deformities ensue. We are reporting a case of a fixed cervical kyphosis after the use of Haldol. PURPOSE: To present a case of a potential acute dystonic reaction temporally associated with Haldol ingestion leading to fixed cervical kyphosis. STUDY DESIGN: This is a case report. METHODS: A patient diagnosed with bipolar disorder presented to the emergency room several times with severe neck pain and stiffness. The neck appeared fixed in flexion with extensive osteophyte formation over a 3-month period. RESULTS: The patient's condition was resolved by a posterior-anterior-posterior surgical approach. It corrected the patient's cervical curvature from 88 degrees to 5 degrees . CONCLUSIONS: Acute dystonic reactions have the potential to apply enough pressure on bone to cause rapid osteophyte formation. PMID- 27664339 TI - Quiescent pluripotent stem cells reside within murine peripheral nerves that can be stimulated to proliferate by recombinant human bone morphogenic protein 2 or by nerve trauma. AB - BACKGROUND: The clinical use of recombinant human bone morphogenic protein 2 (rhBMP-2, Infuse) has been associated with nerve-related complications including new-onset sciatica, and retrograde ejaculation. PURPOSE: To better understand the interaction of rhBMP-2 and peripheral nerves with the intent of making procedures safer. STUDY DESIGN/SETTING: Using a mouse model to examine the direct effect of diluted rhBMP-2 (Infuse) on murine sciatic nerves. METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee. Balb/c mouse sciatic nerves were surgically exposed and 60 ng (in 10 uL) of rhBMP-2 was applied to the nerve. In separate experiments, the sciatic nerves were subjected to mechanical compression using forceps (and not exposed to rhBMP-2). The third group of mice received direct injection of the same amount of rhBMP-2, or sterile saline as a control, into the hamstring area of the posterior thigh without surgery. Mouse limbs with intact sciatic nerve were collected at 24, 48, or 72 hours after treatment for histology processing. A separate set of identically treated sciatic nerves were retrieved from mice at the same time points and cells were isolated by collagenase and trypsin digestion. The isolated cells were cultured in a stem cell medium containing 20% knockout serum and human leukemia inhibitory factor. Immunohistochemical or immunofluorescent cell stains against KLF4, Sox2, c-Myc, and Oct4 were performed on the mouse tissue sections and cell culture slides. In addition, real-time polymerase chain reaction (PCR) was performed to quantify the mRNA expression profiles of the stem cell marker genes in cultured cells. RESULTS: Profound morphological changes of the mouse sciatic nerves were noted after exposure to rhBMP-2, with a rapid and robust cell proliferation within the nerves followed by migration of these cells into surrounding tissue. Immunohistochemical stain revealed strong nuclear stains of KLF4, Sox2, Oct4, and c-Myc on the overwhelming majority of these proliferating cells in the nerve. Intramuscular injections of rhBMP-2 or willful physical compression of the nerves showed similar cell proliferation effects as the direct application of Infuse to the sciatic nerve. The cells in stem cell culture medium grew steadily without feeder cells and appeared fairly uniform. They were adherent to substrate and were motile. Double fluorescent staining on the cells indicated colocalizationof all pairs of the four stem cell markers in the cell nuclei. Real-time PCR confirmed the strong mRNA expressions of KLF4, Sox2, Oct4, and c-Myc in these isolated cells. CONCLUSION: Exposure to BMP-2 causes a marked proliferation of previously quiescent cells within peripheral nerves. These cells simultaneously express KLF4, Sox2, Oct4, and c-Myc, the transcription factors that confer embryonic pluripotency. Work described in the companion paper reveals some of the differentiation capacity of the cells and their likely clinical significance. In addition, the effects of direct exposure of nerves to rhBMP-2 as described here should clearly illuminate the mechanism of BMP-2-related nerve complications. We would suggest that the use of this agent in proximity to known neural structures should only be done with extreme caution. PMID- 27664340 TI - Independent predictors of a clinically significant improvement after lumbar fusion surgery. AB - BACKGROUND CONTEXT: Multiple studies have determined minimum clinically important difference (MCID) thresholds for EuroQOL-5 Dimensions (EQ-5D) scores in lumbar fusion patients. However, a comprehensive understanding of predictors for a clinically significant improvement (CSI) postoperatively does not exist. PURPOSE: To determine medical, radiographic, and surgical predictors for obtaining a CSI following lumbar fusion surgery. STUDY DESIGN: This is a retrospective review of patients who underwent instrumented lumbar fusion. PATIENT SAMPLE: We included patients who underwent lumbar fusion for any indication between 2008 and 2013. OUTCOME MEASURES: Outcome measures included preoperative and postoperative EQ-5D Index scores. MATERIALS AND METHODS: The medical records of patients who received a lumbar fusion for any indication were retrospectively reviewed to identify patient medical and surgical characteristics. A blinded reviewer assessed radiographs for each patient to examine sagittal alignment following fusion. Multivariable logistic regression was used to model the achievement of a CSI based on two commonly cited MCID values. RESULTS: A total of 231 patients fit the inclusion criteria; 58% exceeded an MCID value for an EQ-5D score of 0.100, and 16% exceeded an MCID value of 0.390. Statistically significant independent predictors of not obtaining a CSI for an MCID threshold of 0.100 included a higher preoperative EQ-5D score (odds ratio [OR]=44.8) and L5-S1 fusion (OR=3.3). For an MCID value of 0.390, a higher preoperative EQ-5D score (OR=2,080.8) and a diagnosis of depression (OR=7.1) were predictive of not achieving a CSI, whereas spondylolisthesis (OR=4.1) was predictive of obtaining a CSI postoperatively. For both MCID values, patients who achieved a CSI had better postoperative quality of life (QOL) scores for all metrics measured, despite worse QOL scores preoperatively. CONCLUSIONS: This study is the first to use a combination of medical, surgical, and postoperative sagittal balance variables as determinants for the achievement of a CSI after lumbar fusion. The awareness of these predictors may allow for better patient selection and surgical approach to decrease the probability of acquiring a poor outcome postoperatively. PMID- 27664341 TI - Disparities in reportable quality metrics by insurance status in the primary spine neoplasm population. AB - BACKGROUND CONTEXT: The Centers for Medicare and Medicaid Services (CMS) defines "adverse quality events" as the incidence of certain complications such as postsurgical hematoma or iatrogenic pneumothorax during an inpatient stay. Patient safety indicators (PSI) are a means to measure the incidence of these adverse events. When adverse events occur, reimbursement to the hospital decreases. The incidence of adverse quality events among patients hospitalized for primary spinal neoplasms is unknown. Similarly, it is unclear what the impact of insurance status is on adverse care quality among this patient population. PURPOSE: We aimed to determine the incidence of PSI among patients admitted with primary spinal neoplasms, and to determine the association between insurance status and the incidence of PSI in this population. STUDY DESIGN: This is a retrospective cohort study. PATIENT SAMPLE: We included all patients, 18 years and older, in the Nationwide Inpatient Sample (NIS) who were hospitalized for primary spine neoplasms from 1998 to 2011. OUTCOME MEASURES: Incidence of PSI from 1998 to 2011 served as outcome variable. METHODS: The NIS was queried for all hospitalizations with a diagnosis of primary spinal neoplasm during the inpatient episode from 1998 to 2011. Incidence of PSI was determined using publicly available lists of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Logistic regression models were used to determine the effect of primary payer status on PSI incidence. All comparisons were made between privately insured patients and Medicaid or self-pay patients. RESULTS: We identified 6,095 hospitalizations in which a primary spinal neoplasm was recorded during the inpatient episode. We excluded patients younger than 18 years and those with "other" or "missing" primary insurance status, leaving 5,880 patients for analysis. After adjusting for patient demographics and hospital characteristics, Medicaid or self-pay patients had significantly greater odds of experiencing one or more PSI (odds ratio [OR] 1.81 95% confidence interval [CI] 1.11-2.95) relative to privately insured patients. CONCLUSIONS: Among patients hospitalized for primary spinal neoplasms, primary payer status predicts the incidence of PSI, an indicator of adverse health-care quality used to determine hospital reimbursement by the CMS. As reimbursement continues to be intertwined with reportable quality metrics, identifying vulnerable populations is critical to improving patient care. PMID- 27664342 TI - What is the optimal cutoff value of the axis-line-angle technique for evaluating trunk imbalance in coronal plane? AB - BACKGROUND CONTEXT: Accurately evaluating the extent of trunk imbalance in the coronal plane is significant for patients before and after treatment. We preliminarily practiced a new method, axis-line-angle technique (ALAT), for evaluating coronal trunk imbalance with excellent intra-observer and interobserver reliability. Radiologists and surgeons were encouraged to use this method in clinical practice. However, the optimal cutoff value of the ALAT for determination of the extent of coronal trunk imbalance has not been calculated up to now. PURPOSE: The purpose of this study was to identify the cutoff value of the ALAT that best predicts a positive measurement point to assess coronal balance or imbalance. STUDY DESIGN/SETTING: A retrospective study at a university affiliated hospital was carried out. PATIENT SAMPLE: A total of 130 patients with C7-central sacral vertical line (CSVL) >0 mm and aged 10-18 years were recruited in this study from September 2013 to December 2014. OUTCOME MEASURES: Data were analyzed to determine the optimal cutoff value of the ALAT measurement. METHODS: The C7-CSVL and ALAT measurements were conducted respectively twice on plain film within a 2-week interval by two radiologists. The optimal cutoff value of the ALAT was analyzed via receiver operating characteristic (ROC) curve. Comparison variables were performed with chi-square test between the C7-CSVL and ALAT measurements for evaluating trunk imbalance. Kappa agreement coefficient method was used to test the intra-observer and interobserver agreement of C7-CSVL and ALAT. RESULTS: The ROC curve area for the ALAT was 0.82 (95% confidence interval: 0.753-0.894, p<.001). The maximum Youden index was 0.51, and the corresponding cutoff point was 2.59 degrees . No statistical difference was found between the C7-CSVL and ALAT measurements for evaluating trunk imbalance (p>.05). Intra observer agreement values for the C7-CSVL measurements by observers 1 and 2 were 0.79 and 0.91 (p<.001), respectively, whereas intra-observer agreement values for the ALAT measurements were both 0.89 by observers 1 and 2 (p<.001). The interobserver agreement values for the first and second measurements with the C7 CSVL were 0.78 and 0.85 (p<.001), respectively, whereas the interobserver agreement values for the first and second measurements with the ALAT were 0.91 and 0.88 (p<.001), respectively. CONCLUSIONS: The newly developed ALAT provided an acceptable optimal cutoff value for evaluating trunk imbalance in the coronal plane with a high level of intra-observer and interobserver agreement, which suggests that the ALAT is suitable for clinical use. PMID- 27664343 TI - Unusual presentation of osteoblastoma as vertebra plana-a case report and review of literature. AB - BACKGROUND: Osteoblastoma is rare and accounts for 3% of all benign tumors and 1% of all bone tumors. The spine is the most common site of occurrence, constituting 32% to 45% of all osteoblastomas. It has a strong predilection for the posterior elements, most often occurring in the lumbar spine. METHOD: In this case report, we describe an unusual presentation of spinal osteoblastoma presenting as thoracic T9 vertebra plana in a 20-year-old female. She presented with discomfort over the midback with unsteadiness of gait. The patient underwent detailed investigations including computed tomography (CT), magnetic resonance imaging, and CT-guided biopsy. To our knowledge, this is the first case report of vertebra plana due to spinal osteoblastoma in the English literature. RESULT: The patient successfully underwent posterior decompression of T9 with laminectomy followed by minimally invasive surgery posterior instrumentation from T7 to T11. Histopathology of the intraoperative specimen was consistent with osteoblastoma. The patient had an uneventful postoperative recovery and no evidence of tumor recurrence could be demonstrated on positron emission tomography scan at 15 months' follow-up. CONCLUSION: In conclusion, the differential diagnosis for vertebra plana is extensive and we add spinal osteoblastoma as another etiology to the existing list. Diagnosis and treatment of vertebra plana involve multimodality radiological imaging, and careful histological and surgical evaluation to identify the underlying etiology. PMID- 27664344 TI - Leapfrogging into new territory: How Mascarene ridged frogs diversified across Africa and Madagascar to maintain their ecological niche. AB - The Mascarene ridged frog, Ptychadena mascareniensis, is a species complex that includes numerous lineages occurring mostly in humid savannas and open forests of mainland Africa, Madagascar, the Seychelles, and the Mascarene Islands. Sampling across this broad distribution presents an opportunity to examine the genetic differentiation within this complex and to investigate how the evolution of bioclimatic niches may have shaped current biogeographic patterns. Using model based phylogenetic methods and molecular-clock dating, we constructed a time calibrated molecular phylogenetic hypothesis for the group based on mitochondrial 16S rRNA and cytochrome b (cytb) genes and the nuclear RAG1 gene from 173 individuals. Haplotype networks were reconstructed and species boundaries were investigated using three species-delimitation approaches: Bayesian generalized mixed Yule-coalescent model (bGMYC), the Poisson Tree Process model (PTP) and a cluster algorithm (SpeciesIdentifier). Estimates of similarity in bioclimatic niche were calculated from species-distribution models (maxent) and multivariate statistics (Principal Component Analysis, Discriminant Function Analysis). Ancestral-area reconstructions were performed on the phylogeny using probabilistic approaches implemented in BioGeoBEARS. We detected high levels of genetic differentiation yielding ten distinct lineages or operational taxonomic units, and Central Africa was found to be a diversity hotspot for these frogs. Most speciation events took place throughout the Miocene, including "out-of Africa" overseas dispersal events to Madagascar in the East and to Sao Tome in the West. Bioclimatic niche was remarkably well conserved, with most species tolerating similar temperature and rainfall conditions common to the Central African region. The P. mascareniensis complex provides insights into how bioclimatic niche shaped the current biogeographic patterns with niche conservatism being exhibited by the Central African radiation and niche divergence shaping populations in West Africa and Madagascar. Central Africa, including the Albertine Rift region, has been an important center of diversification for this species complex. PMID- 27664345 TI - A multilocus phylogeny of Podoctidae (Arachnida, Opiliones, Laniatores) and parametric shape analysis reveal the disutility of subfamilial nomenclature in armored harvestman systematics. AB - The taxonomy and systematics of the armored harvestmen (suborder Laniatores) are based on various sets of morphological characters pertaining to shape, armature, pedipalpal setation, and the number of articles of the walking leg tarsi. Few studies have tested the validity of these historical character systems in a comprehensive way, with reference to an independent data class, i.e., molecular sequence data. We examined as a test case the systematics of Podoctidae, a family distributed throughout the Indo-Pacific. We tested the validity of the three subfamilies of Podoctidae using a five-locus phylogeny, and examined the evolution of dorsal shape as a proxy for taxonomic utility, using parametric shape analysis. Here we show that two of the three subfamilies, Ibaloniinae and Podoctinae, are non-monophyletic, with the third subfamily, Erecananinae, recovered as non-monophyletic in a subset of analyses. Various genera were also recovered as non-monophyletic. As first steps toward revision of Podoctidae, the subfamilies Erecananinae Roewer, 1912 and Ibaloniinae Roewer, 1912 are synonymized with Podoctinae Roewer, 1912 new synonymies, thereby abolishing unsubstantiated subfamilial divisions within Podoctidae. We once again synonymize the genus Paralomanius Goodnight & Goodnight, 1948 with Lomanius Roewer, 1923 revalidated. We additionally show that eggs carried on the legs of male Podoctidae are not conspecific to the males, falsifying the hypothesis of paternal care in this group. PMID- 27664346 TI - Phylogeographic structure across one of the largest intact tropical savannahs: Molecular and morphological analysis of Australia's iconic frilled lizard Chlamydosaurus kingii. AB - The spectacular threat display of the savannah specialist Australo-Papuan frilled lizards has made them one of the world's most iconic reptiles. They are increasingly used as a model system for research in evolutionary biology and ecology but little is known of their population structure. Their distribution across northern Australia and southern New Guinea also provides an opportunity to examine biogeographic patterns as they relate to the large-scale movement of savannah habitat during the Plio/Pleistocene and the associated increase in aridity. We generated sequence data for one mitochondrial and four nuclear DNA loci (5052 base pairs) for 83 frilled lizards sampled throughout their range. We also quantified body proportion variation for 279 individuals. Phylogenetic analyses based on maximum likelihood and Bayesian species-tree methods revealed three shallow clades that replace each other across the monsoon tropics. We found the expected pattern of male biased sexual size dimorphism in both maximum body size and head size but there was no sexual dimorphism in overall body shape or in frill size, relative to head size, supporting the hypothesis that the frill is used primarily as a threat display rather than a sexual display. The genetic clades are broadly consistent with known clinal variation in frill color that gradually shifts from west to east (red, orange, yellow/white) but otherwise show little morphological differentiation in body proportion measures. The biogeographic breaks between clades occur at the Carpentaria Gap and the lowlands surrounding the Ord River, and our ecological niche modeling predicts lower habitat suitability for C. kingii in these regions. While this biogeographic pattern is consistent with numerous other taxonomic groups in northern Australia, the overall low genetic diversity in frilled lizards across the entire monsoon tropics and southern New Guinea contrasts starkly to patterns seen in other terrestrial vertebrates. Extremely low intra-clade genetic diversity over vast geographic areas is indicative of recent gene flow that would likely have been facilitated by widespread savannah during interglacials, or alternatively may reflect population bottlenecks induced by extreme aridity during Pleistocene glacials. The shallow divergence between Australian and New Guinean samples is consistent with recent connectivity between Australia and New Guinea that would have been possible via a savannah corridor across the Torres Strait. Based on our molecular and morphological data, we do not support taxonomic recognition of any of the frilled lizard clades and instead consider C. kingii a single species with shallow phylogeographic structure and clinal variation in frill color. PMID- 27664347 TI - Range size heritability and diversification patterns in the liverwort genus Radula. AB - Why some species exhibit larger geographical ranges than others, and to what extent does variation in range size affect diversification rates, remains a fundamental, but largely unanswered question in ecology and evolution. Here, we implement phylogenetic comparative analyses and ancestral area estimations in Radula, a liverwort genus of Cretaceous origin, to investigate the mechanisms that explain differences in geographical range size and diversification rates among lineages. Range size was phylogenetically constrained in the two sub-genera characterized by their almost complete Australasian and Neotropical endemicity, respectively. The congruence between the divergence time of these lineages and continental split suggests that plate tectonics could have played a major role in their present distribution, suggesting that a strong imprint of vicariance can still be found in extant distribution patterns in these highly mobile organisms. Amentuloradula, Volutoradula and Metaradula species did not appear to exhibit losses of dispersal capacities in terms of dispersal life-history traits, but evidence for significant phylogenetic signal in macroecological niche traits suggests that niche conservatism accounts for their restricted geographic ranges. Despite their greatly restricted distribution to Australasia and Neotropics respectively, Amentuloradula and Volutoradula did not exhibit significantly lower diversification rates than more widespread lineages, in contrast with the hypothesis that the probability of speciation increases with range size by promoting geographic isolation and increasing the rate at which novel habitats are encountered. We suggest that stochastic long-distance dispersal events may balance allele frequencies across large spatial scales, leading to low genetic structure among geographically distant areas or even continents, ultimately decreasing the diversification rates in highly mobile, widespread lineages. PMID- 27664348 TI - Perceptual Learning of Facial Expressions. AB - Perceptual learning is a phenomenon in which intensive training for a perceptual task may lead to significant improvement in the task performance. So far, the characteristics of the perceptual learning of facial expressions have not been investigated. In the current study, we trained subjects to distinguish facial expressions. With eight days of training, the subjects' discrimination performance improved significantly, and this improvement was generalized to faces with the same expression but different gender as the trained face. In the second experiment, we further examined the transfer of the learning effect between faces with different expression intensities. We found that the learning effect of happiness can be transferred from the high-intensity face to the low-intensity face, but the reverse was not true. Importantly, in all experiments, we measured the performance immediately after training and one month after training. The results showed that all learning effects and transfers were able to persist for at least one month, which implied that these findings revealed the long-term mechanisms of training. These results revealed the characteristics of facial expression learning and shed light on the mechanisms of perceptual learning for high-level vision. PMID- 27664349 TI - Binocular functional architecture for detection of contrast-modulated gratings. AB - Combination of signals from the two eyes is the gateway to stereo vision. To gain insight into binocular signal processing, we studied binocular summation for luminance-modulated gratings (L or LM) and contrast-modulated gratings (CM). We measured 2AFC detection thresholds for a signal grating (0.75c/deg, 216ms) shown to one eye, both eyes, or both eyes out-of-phase. For LM and CM, the carrier noise was in both eyes, even when the signal was monocular. Mean binocular thresholds for luminance gratings (L) were 5.4dB better than monocular thresholds - close to perfect linear summation (6dB). For LM and CM the binocular advantage was again 5-6dB, even when the carrier noise was uncorrelated, anti-correlated, or at orthogonal orientations in the two eyes. Binocular combination for CM probably arises from summation of envelope responses, and not from summation of these conflicting carrier patterns. Antiphase signals produced no binocular advantage, but thresholds were about 1-3dB higher than monocular ones. This is not consistent with simple linear summation, which should give complete cancellation and unmeasurably high thresholds. We propose a three-channel model in which noisy monocular responses to the envelope are binocularly combined in a contrast-weighted sum, but also remain separately available to perception via a max operator. Vision selects the largest of the three responses. With in-phase gratings the binocular channel dominates, but antiphase gratings cancel in the binocular channel and the monocular channels mediate detection. The small antiphase disadvantage might be explained by a subtle influence of background responses on binocular and monocular detection. PMID- 27664350 TI - The saccadic size-latency phenomenon explored: Proximal target size is a determining factor in the saccade latency. AB - Saccade latencies are known to increase for targets presented close to fixation. Recently, it was shown that not only target eccentricity, but the size of a proximal saccade target also plays a crucial role: latencies increase rapidly with increasing target size. Interestingly, these latency increases are greater than those typically found for other supra-threshold manipulations of target properties. Here we evaluate to what extent this phenomenon is distinct from known delays in saccade initiation and whether the phenomenon is truly related to the size of a proximal target. In Experiment 1 we focus on the importance of the required amplitude. Employing a saccade adaptation paradigm we find that the required amplitude is not a determining factor. Focusing on the role of size, in Experiment 2, we find that while latency increases are strongest for targets elongated in the direction of the fovea, elongations perpendicular to this direction also lead to an increase in latencies. Finally, in Experiment 3 we verify that the latency increases are driven by the properties of the saccade target rather than visual input in general. Together these experiments provide converging evidence that the current phenomenon is both novel and a consequence of the relation between proximal target size and its eccentricity. PMID- 27664351 TI - The effects of monocular viewing on hand-eye coordination during sequential grasping and placing movements. AB - The contribution of binocular vision to the performance of reaching and grasping movements has been examined previously using single reach-to-grasp movements. However, most of our daily activities consist of more complex action sequences, which require precise temporal linking between the gaze behaviour and manual action phases. Many previous studies found a stereotypical hand-eye coordination pattern, such that the eyes move prior to the reach initiation. Moving the eyes to the target object provides information about its features and location, which can facilitate the predictive control of reaching and grasping. This temporal coordination pattern has been established for the performance of sequential movements performed during binocular viewing. Here we manipulated viewing condition and examined the temporal hand-eye coordination pattern during the performance of a sequential reaching, grasping, and placement task. Fifteen participants were tested on a sequencing task while eye and hand movements were recorded binocularly using a video-based eyetracker and a motion capture system. Our results showed that monocular viewing disrupted the temporal coordination between the eyes and the hand during the place-to-reach transition phase. Specifically, the gaze shift was delayed during monocular compared to binocular viewing. The shift in gaze behaviour may be due to increased uncertainty associated with the performance of the placement task because of increased vergence error during monocular viewing, which was evident in all participants. These findings provide insight into the role of binocular vision in predictive control of sequential reaching and grasping movements. PMID- 27664352 TI - Go-getters and procrastinators: Investigating individual differences in visual cognition across university semesters. AB - University-based psychological research typically relies on the participation of undergraduate students for data collection. Using this particular sample brings with it several possible issues, including the self-scheduling done by the participants. Research on performance between students who sign up early versus late in the semester has been inconsistent. Some research report benefits for early participant semesters, while others find no differences between the two groups. Anecdotally, it seems that the former holds true, as many researchers worry about the data collected late in the semester, sometimes opting for more motivated earlier participants in the next semester. The purpose of our study was to examine for the effect of time of semester across a well-known set of visual cognition tasks. To do so, participants completed canonical versions of a rapid serial visual presentation task, a flanker task, an additional singleton paradigm task, a multiple object tracking task and a visual working memory task. These tasks were chosen as typical measures of executive control, temporal selectivity, visual working memory capacity, resistance to distraction, and attentional capacity. Crucially, we correlated task performance with time of semester students chose to participate. Our results demonstrate that there were no significant differences in any of the tasks across semester timing. Furthermore, our findings support the validity of cognitive research relying on the system of recruiting undergraduate students from volunteer pools where students can self select the time of the semester they undertake the experiments. PMID- 27664353 TI - Geometrical features underlying the perception of collinearity. AB - The magnitude of the Poggendorff bias in perceived collinearity was measured with a 2AFC task and roving pedestal, and was found to be in the region of 6-8deg, within the range of previous estimates. Further measurements dissected the bias into several components: (1) The small (~1deg) repulsion of the orientation of the pointer from the parallel, probably localized in the part of the line near the intersection (2) A small (<1deg) location bias affecting the intersection of pointers and inducing lines; and (3) A larger (>1deg) bias in the orientation of virtual lines crossing the gap between two parallels, towards the orientation of the parallels, or equivalently (4) An orthogonal bias in actively constructing a virtual line across the gap. We conclude that orientation repulsion by itself is an inadequate explanation of the Poggendorff effect, and that a full explanation must take account of the way in which observers construct virtual lines in visual space in order to carry out elementary geometrical tasks such as extrapolation. PMID- 27664354 TI - ? PMID- 27664355 TI - ? PMID- 27664356 TI - [Information and communication technology and health of the elderly]. AB - New technologies offer many advantages, especially in terms of animation in elderly care homes. Consoles and digital tablets used without any medical implication were the subject of a literature review on their impact on the health of the elderly.. PMID- 27664357 TI - [Robotics and improvement of the quality of geriatric care]. AB - New technologies offer innovations to improve the care of the elderly with Alzheimer's or and other forms of dementia. Robots, endowed with features such as monitoring of physiological parameters, cognitive training or occupational therapy, have appeared. They are not, however, intended to replace humans. Still underutilized, these robots are in development, much like the digital literacy of the elderly. PMID- 27664359 TI - [Connected home, monitoring and improved care]. AB - New technologies offer a new approach to healthcare management that benefits the patient, especially at home: better living spaces, improved safety and preservation of communication. Professionals concerned and family caregivers should be trained in these new technologies to discover and explore everyday their possibilities and uses. PMID- 27664358 TI - [Neuropsychiatric disorders and technological solutions]. AB - Innovative new tools today allow better clinical evaluation. Indeed, new information and communication technology is particularly interesting for the screening, monitoring and management of neuropsychiatric disorders of the elderly. A personalised approach to patients can further enhance their adherence and involvement. PMID- 27664360 TI - [Serious game, a link between institution and home]. AB - Serious game is a personal innovative technology to facilitate learning and social interaction. It can be used in a patient's home or in an institution. This training tool can also be developed for health professionals, especially accommodation facilities for the elderly. The objective is to integrate knowledge and know-how. PMID- 27664361 TI - [Pain in mental health in the elderly]. AB - Consideration of pain in mental health proves fundamental in psychiatry, a fortiori psychogeriatrics. The elderly person is often confronted with a painful existential situation and the experience of physical pain that go unheard. This algic component of somatic origin is still, like moral pain, too trivialized, because of becoming elderly too fast. The culture of the fight against pain needs to be developed further as well as the practical training of doctors and caregivers. PMID- 27664362 TI - [Announcement of the death of a loved one to a geriatric inpatient]. AB - A geriatric inpatient may learn of the death of a loved one. The medical team must assess what is the kindest way to announce it to the patient who is already fragile. It will address the patient's relationship with the loved one, the right to information, and the position of the family. Accompanying the patient through this ordeal is also important. This delicate issue needs the reflection of the team. PMID- 27664363 TI - [Antibiotic prescription usage and assessment in geriatric patients]. AB - Due to the high risk of infection, the geriatric population is regularly subjected to antibiotics. Faced with bacterial resistance, particularly among elderly dependent patients, it is essential to promote proper use and correct prescription of antibiotics. A study evaluated antibiotic prescription in a geriatric hospital with 598 beds and highlighted the importance of collaboration between geriatricians and infectious disease specialists. PMID- 27664365 TI - ? PMID- 27664364 TI - [Role of the nurse in the prevention of dependence]. AB - Preventing frailty in elderly people to delay their dependency is one of the main missions of the Gerontopole, a centre of expertise for gerontology, in Toulouse. The proposed actions are simple to put in place and the nurses are autonomous in carrying out assessments. Nursing expertise has also been developed within the centre. PMID- 27664366 TI - ? PMID- 27664367 TI - Modifying interpretation biases in body dysmorphic disorder: Evaluation of a brief computerized treatment. AB - Individuals meeting diagnostic criteria for body dysmorphic disorder (BDD; N = 40) were enrolled in a randomized, four-session trial comparing interpretation bias modification (IBM) training designed to target social evaluation- and appearance-related interpretation biases with a placebo control training condition (PC). Sessions took place over the course of two weeks (two sessions per week). Analyses indicated that, relative to the PC condition, IBM led to a significant increase in benign biases and reduction in threat biases at post treatment. IBM also led to greater reductions in BDD symptoms compared to PC, though this effect was present at high but not low levels of pre-treatment BDD symptoms. Additionally, compared to PC, IBM led to lower urge to check and lower fear in response to an in vivo appearance-related stressor (having their picture taken from different angles), though the latter effect was present only among those reporting elevated fear at pre-treatment. The effects of treatment on interpretation biases and BDD symptoms were largely maintained at a one-month follow-up assessment. Moderated-mediation analyses showed that change in threat bias mediated the effect of condition on post-treatment symptoms for individuals high in pre-treatment BDD symptoms. The current study provides preliminary support for the efficacy of IBM for BDD. PMID- 27664368 TI - One pot oxidative dehydration - oxidation of polyhydroxyhexanal oxime to polyhydroxy oxohexanenitrile: A versatile methodology for the facile access of azasugar alkaloids. AB - A unique oxidative dehydration-oxidation of polyhydroxy-oxime (7) to the corresponding ketonitrile (8) in one pot is reported for the first time in carbohydrate literature. Key ketonitrile intermediate (8) upon palladium hydroxide mediated cascade reaction afforded 1-deoxynojirimycin (DNJ) 1b in moderate diastereoselectivity. The cascade reaction involves the conversion of nitrile to amine, heteroannulation, reduction of the imine and subsequent debenzylation to furnish the azasugars. This oxidative dehydration-oxidation and reductive heteroannulation methodology is successfully utilized for the total synthesis of 1-deoxynojirimycin (1b), miglitol (2) and miglustat (3). PMID- 27664369 TI - Impairment of decision making associated with disruption of phase-locking in the anterior cingulate cortex in viscerally hypersensitive rats. AB - Visceral hypersensitivity (VH) is a key factor of irritable bowel syndrome (IBS). Previous studies have identified an enhanced response of anterior cingulate cortex (ACC) to colorectal distension in VH rats, which can be observed up to 7weeks following colonic anaphylaxis, independent of colonic inflammation. The induction of VH produces a change in the ability to induce subsequent synaptic plasticity at the ACC circuitry. In clinical practice, a positive link between IBS and cognitive impairments has been noted for years, but no animal model has been reported. Decision-making is a valuable model for monitoring higher-order cognitive functions in animals, which depends on the integrated function of several sub-regions of the ACC and amygdala. Using rat gambling task (RGT) in the present study, we observed an impairment of decision-making behavior in VH rats. Electrophysiological study showed a reduction of long-term potentiation in the basolateral amygdala (BLA)-ACC synapses in VH rats. Multiple-electrode array recordings of local field potential (LFP) in both BLA and ACC were also performed in freely behaving rats. Spike-field coherence (SFC) analysis revealed chronic visceral pain led to disruption of ACC spike timing and BLA local theta oscillation. Finally, cross-correlation analysis revealed that VH was associated with suppressed synchronization of theta oscillation between the BLA and ACC, indicating reduced neuronal communications between these two regions under the VH state. The present results demonstrate that functional disturbances in BLA-ACC neural circuitry may be relevant causes for the deficits in decision-making in chronic pain state. PMID- 27664370 TI - Evidence of metabolic microevolution of the limpet Nacella concinna to naturally high heavy metal levels in Antarctica. AB - The gastropod Nacella concinna is the most conspicuous macroinvertebrate of the intertidal zone of the Antarctic Peninsula and adjacent islands. Naturally high levels of copper and cadmium in coastal marine ecosystems are accumulated in N. concinna tissues. We aimed to study the effects of metal cations on N. concinna arginase in the context of possible adaptive microevolution. Gills and muscle had the highest argininolytic activity, which was concentrated in the cytosol in both tissues. Gills had the highest levels of arginase and may be involved in the systemic control of l-arginine levels. The relatively high argininolytic activity of the N. concinna muscular foot, with KM=25.3+/-3.4mmolL-1, may be involved in the control of l-arginine levels during phosphagen breakdown. N. concinna arginases showed the following preferences for metal cations: Ni2+>Mn2+>Co2+>Cu2+ in muscle and Mn2+>Cu2+ in gills. Cu2+ activation is a unique characteristic of N. concinna arginases, as copper is a potent arginase inhibitor. Cu2+ partly neutralized N. concinna arginase inhibition by Cd2+, worked synergistically in muscle arginase activation by Co2+ and neutralized muscle arginase activation by Ni2+. Mn2+ was able to activate muscle arginase in the presence of Fe3+ and Pb2+. The selection of arginases that are activated by Cu2+ and resistant to inhibition by Cd2+ in the presence of Cu2+ over evolutionary timescales may have favored N. concinna occupation of copper- and cadmium-rich niches. PMID- 27664371 TI - Effect of diet on carboxylesterase activity of tadpoles (Rhinella arenarum) exposed to chlorpyrifos. AB - An outdoor microcosm was performed with tadpoles (Rhinella arenarum) exposed to 125MUgL-1 chlorpyrifos and fed two types of food, i.e., lettuce (Lactuca sativa) and a formulated commercial pellet. Acetylcholinesterase (AChE) and carboxylesterase (CbE) activities were measured in liver and intestine after 10 days of pesticide exposure. Non-exposed tadpoles fed lettuce had an intestinal AChE activity almost two-fold higher than that of pellet-fed tadpoles. No significant differences were observed, however, in liver AChE activity between diets. Likewise, intestinal CbE activity - measured using two substrates, i.e. 1 naphthyl acetate (1-NA) and 4-nitrophenyl valerate (4-NPV) - was higher in tadpoles fed lettuce than in those fed pellets. However, the diet-dependent response of liver CbE activity was opposite to that in the intestine. Chlorpyrifos caused a significant inhibition of both esterase activities, which was tissue- and diet-specific. The highest inhibition degree was found in the intestinal AChE and CbE activities of lettuce-fed tadpoles (42-78% of controls) compared with pellet-fed tadpoles (<60%). Although chlorpyrifos significantly inhibited liver CbE activity of the group fed lettuce, this effect was not observed in the group fed pellets. In general, intestinal CbE activity was more sensitive to chlorpyrifos inhibition than AChE activity. This finding, together with the high levels of basal CbE activity found in the intestine, may be understood as a detoxification system able to reduce intestinal OP uptake. Moreover, the results of this study suggest that diet is a determinant factor in toxicity testing with tadpoles to assess OP toxicity, because it modulates levels of this potential detoxifying enzyme activity. PMID- 27664372 TI - Deformable regions of interest with multiple points for tissue tracking in echocardiography. AB - By tracking echocardiography images more accurately and stably, we can better assess myocardial functions. In this paper, we propose a new tracking method with deformable Regions of Interest (ROIs) aiming at rational pattern matching. For this purpose we defined multiple tracking points for an ROI and regarded these points as nodes in the Meshfree Method to interpolate displacement fields. To avoid unreasonable distortion of the ROI caused by noise and perturbation in echo images, we introduced a stabilization technique based on a nonlinear strain energy function. Examples showed that the combination of our new tracking method and stabilization technique provides competitive and stable tracking. PMID- 27664373 TI - How to map and ablate left ventricular summit arrhythmias. PMID- 27664374 TI - Direct visualization to facilitate left ventricular summit ablation: Seeing is believing! PMID- 27664375 TI - Expression profiles and hormonal regulation of tobacco expansin genes and their involvement in abiotic stress response. AB - Changes in the expression levels of tobacco expansin genes NtEXPA1, NtEXPA4, NtEXPA5, and NtEXPA6 were studied in different organs of tobacco (Nicotiana tabacum L.) as well as in response to phytohormone and stress treatments. It was shown that NtEXPA1, NtEXPA4 and NtEXPA5 transcripts were predominantly expressed in the shoot apices and young leaves, but almost absent in mature leaves and roots. The NtEXPA6 mRNA was found at high levels in calluses containing a large number of undifferentiated cells, but hardly detectable in the leaves of different ages and roots. In young leaves, expression levels of NtEXPA1, NtEXPA4 and NtEXPA5 genes were induced by cytokinins, auxins and gibberellins. Cytokinins and auxins were also found to increase NtEXPA6 transcripts in young leaves but to the much lower levels than the other expansin mRNAs. Expression analysis demonstrated that brassinosteroid phytohormones were able either to up-regulate or to down-regulate expression of different expansins in leaves of different ages. Furthermore, transcript levels of NtEXPA1, NtEXPA4, and NtEXPA5 genes were increased in response to NaCl, drought, cold, heat, and 10MUM abscisic acid (ABA) treatments but reduced in response to more severe stresses, i.e. cadmium, freezing, and 100MUM ABA. In contrast, no substantial changes were found in NtEXPA6 transcript level after all stress treatments. In addition, we examined the involvement of tobacco expansins in the regulation of abiotic stress tolerance by transgenic approaches. Transgenic tobacco plants with constitutive expression of NtEXPA1 and NtEXPA5 exhibited improved tolerance to salt stress: these plants showed higher growth indices after NaCl treatment and minimized water loss by reducing stomatal density. In contrast, NtEXPA4-silenced plants were characterized by a considerable growth reduction under salinity and enhanced water loss. Our findings indicate that expression levels of all studied tobacco expansins genes are modulated by plant hormones whereas NtEXPA1, NtEXPA4, and NtEXPA5 expansins may be involved in the regulation of stress tolerance in tobacco plants. PMID- 27664376 TI - p53 and p16Ink4a/p19Arf Loss Promotes Different Pancreatic Tumor Types from PyMT Expressing Progenitor Cells. AB - In human studies and mouse models, the contributions of p53 and p16Ink4a/p19Arf loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs. Concurrent loss of p53 and Ink4a/Arf resembles loss of p53 alone, suggesting that Ink4a/Arf loss has no additive effect to PACC progression. Our results show that specific tumor suppressor genotypes provocatively influence the tumor biological phenotypes in pancreatic progenitor cells. Additionally, in a mouse model of beta-cell hyperplasia, we demonstrate that p53 and Ink4a/Arf play cooperative roles in constraining the progression of PanNETs. PMID- 27664377 TI - Current application of exhaled nitric oxide in clinical practice. PMID- 27664378 TI - Linking impaired skin barrier function to esophageal allergic inflammation via IL 33. PMID- 27664380 TI - Binding interaction of ramipril with bovine serum albumin (BSA): Insights from multi-spectroscopy and molecular docking methods. AB - The binding interaction between a typical angiotensin-converting enzyme inhibitor (ACEI), ramipril, and a transport protein, bovine serum albumin (BSA), was studied in vitro using UV-vis absorption spectroscopy, steady-state fluorescence spectroscopic titration, synchronous fluorescence spectroscopy, three dimensional fluorescence spectroscopy, circular dichroism and molecular docking under the imitated physiological conditions (pH=7.4). The experimental results suggested that the intrinsic fluorescence of BSA was quenched by ramipril thought a static quenching mechanism, indicating that the stable ramipril-BSA complex was formed by the intermolecular interaction. The number of binding sites (n) and binding constant of ramipril-BSA complex were about 1 and 3.50*104M-1 at 298K, respectively, suggesting that there was stronger binding interaction of ramipril with BSA. The thermodynamic parameters together with molecular docking study revealed that both van der Waal's forces and hydrogen bonding interaction dominated the formation of the ramipril-BSA complex and the binding interaction of BSA with ramipril is enthalpy-driven processes due to |DeltaH degrees |>|TDeltaS degrees | and DeltaG degrees <0. The spatial distance between ramipril and BSA was calculated to be 3.56nm based on Forster's non-radiative energy transfer theory. The results of the competitive displacement experiments and molecular docking confirmed that ramipril inserted into the subdomain IIA (site I) of BSA, resulting in a slight change in the conformation of BSA but BSA still retained its secondary structure alpha-helicity. PMID- 27664381 TI - Moderate high or low maternal protein diets change gene expression but not the phenotype of skeletal muscle from porcine fetuses. AB - The aim of our study was to characterize the immediate phenotypic and adaptive regulatory responses of fetuses to different in utero conditions reflecting inadequate maternal protein supply during gestation. The gilts fed high- (250% above control) or low- (50% under control) protein diets isoenergetically adjusted at the expense of carbohydrates from the day of insemination until the fetuses were collected at day 64 or 94 of gestation. We analyzed body composition, histomorphology, biochemistry, and messenger RNA (mRNA) expression of fetal skeletal muscle. Both diets had only marginal effects on body composition and muscular cellularity of fetuses including an unchanged total number of myofibers. However, mRNA expression of myogenic regulatory factors (MYOG, MRF4, P <= 0.1), IGF system (IGF1, IGF1R, P <= 0.05) and myostatin antagonist FST (P = 0.6, in males only) was reduced in the fetal muscle exposed to a maternal low-protein diet. As a result of excess protein, MYOD, MYOG, IGF1R, and IGFBP5 mRNA expression (P <= 0.05) was upregulated in fetal muscle. Differences in muscular mRNA expression indicate in utero regulatory adaptive responses to maternal diet. Modulation of gene expression immediately contributes to the maintenance of an appropriate fetal phenotype that would be similar to that observed in the control fetuses. Moreover, we suggest that the modified gene expression in fetal skeletal muscle can be viewed as the origin of developmental muscular plasticity involved in the concept of fetal programming. PMID- 27664383 TI - Autoimmunity-Basics and link with periodontal disease. AB - Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. PMID- 27664382 TI - A miRNA target network putatively involved in follicular atresia. AB - In a previous microarray study, we identified a subset of micro RNAS (miRNAs), which expression was distinctly higher in atretic than healthy follicles of cattle. In the present study, we investigated the involvement of those miRNAs in granulosa and theca cells during atresia. Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) confirmed that miR-21-5p/-3p, miR-150, miR 409a, miR-142-5p, miR-378, miR-222, miR-155, and miR-199a-5p were expressed at higher levels in atretic than healthy follicles (9-17 mm, classified based on steroidogenic capacity). All miRNAs except miR-21-3p and miR-378 were expressed at higher levels in theca than granulosa cells. The expression of 13 predicted miRNA targets was determined in follicular cells by RT-qPCR, revealing downregulation of HIF1A, ETS1, JAG1, VEGFA, and MSH2 in either or both cell types during atresia. Based on increases in miRNA levels simultaneous with decreases in target levels in follicular cells, several predicted miRNA target interactions were confirmed that are putatively involved in follicular atresia, namely miR 199a-5p/miR-155-HIF1A in granulosa cells, miR-155/miR-222-ETS1 in theca cells, miR-199a-5p-JAG1 in theca cells, miR-199a-5p/miR-150/miR-378-VEGFA in granulosa and theca cells, and miR-155-MSH2 in theca cells. These results offer novel insight on the involvement of miRNAs in follicle development by identifying a miRNA target network that is putatively involved in follicle atresia. PMID- 27664385 TI - Assessment of anoxia tolerance and photoperiod dependence of GABAergic polarity in the pond snail Lymnaea stagnalis. AB - The pond snail Lymnaea stagnalis is reported to be anoxia-tolerant and if the tolerance mechanism is similar to that of the anoxia-tolerant painted turtle, GABA should play an important role. A potentially confounding factor investigating the role of GABA in anoxia tolerance are reports that GABA has both inhibitory and excitatory effects within L. stagnalis central ganglion. We therefore set out to determine if seasonality or photoperiod has an impact on: 1) the anoxia-tolerance of the intact pond snail, and 2) the response of isolated neuroganglia cluster F neurons to exogenous GABA application. L. stagnalis maintained on a natural summer light cycle were unable to survive any period of anoxic exposure, while those maintained on a natural winter light cycle survived a maximum of 4h. Using intracellular sharp electrode recordings from pedal ganglia cluster F neurons we show that there is a photoperiod dependent shift in the response to GABA. Snails exposed to a 16h:8h light:dark cycle in an environmental chamber (induced summer phenotype) exhibited hyperpolarizing inhibitory responses and those exposed to a 8h:16h light:dark cycle (induced winter phenotype) exhibited depolarizing excitatory responses to GABA application. Using gramicidin-perforated patch recordings we also found a photoperiod dependent shift in the reversal potential for GABA. We conclude that the opposing responses of L. stagnalis central neurons to GABA results from a shift in intracellular chloride concentration that is photoperiod dependent and is likely mediated through the relative efficacy of cation chloride co transporters. Although the physiological ramifications of the photoperiod dependent shift are unknown this work potentially has important implications for the impact of artificial light pollution on animal health. PMID- 27664384 TI - Prognostic factors of macrophage activation syndrome, at the time of diagnosis, in adult patients affected by autoimmune disease: Analysis of 41 cases collected in 2 rheumatologic centers. AB - Macrophage activation syndrome (MAS) is a rare, life-threatening disease in which early diagnosis and aggressive therapeutic strategy may improve the outcome. Due to its rarity, epidemiologic data are still lacking. Hyperferritinemia is frequently associated with MAS and might modulate the cytokine storm, which is involved in the development of multiple organ failure. In this paper, we investigated clinical data, treatments, and outcome of a homogeneous cohort of 41 adult MAS patients, complicating autoimmune rheumatic diseases. MAS-related death occurred in 17 patients (42.5%) during the follow-up, and older age and increased serum ferritin levels, at the time of diagnosis, were significantly associated with mortality. In conclusion, adult MAS is associated with high mortality rate. Some clinical features at diagnosis may be predictive of MAS-associated death. PMID- 27664386 TI - Structural elucidation of the impurities in Enzalutamide bulk drug and the development, validation of corresponding HPLC method. AB - As the first approved androgen receptor(AR) signalling inhibitor, Enzalutamide was approved by the US Food and Drug Administration as an anticancer drug used to treat castration-resistant prostate cancer in 2012. In this manuscript, six potential impurities of Enzalutamide including process impurities and degradation products were studied. The structures of six impurities obtained by synthesis were characterized and confirmed by IR, NMR and MS techniques. In addition, an efficient chromatographic method to separate and quantify these impurities was developed, which achieved on Inertsil ODS-3 column (250mm*4.6mm,5MUm) in gradient mode with a mixture of acetonitrile and the ammonium acetate buffer (10mM, pH adjusted to 4.0 with glacial acetic acid). The method was validated with respect to specificity, precision, accuracy, and sensitivity and satisfactory result was achieved. The method was demonstrated to be applicable in routine quality control and stability evaluation of Enzalutamide. PMID- 27664387 TI - Association between lifetime alcohol consumption and prostate cancer risk: A case control study in Montreal, Canada. AB - BACKGROUND: Alcohol intake may increase the risk of prostate cancer (PCa). Many previous studies harbored important methodological limitations. METHODS: We conducted a population-based case-control study of PCa comprising 1933 cases and 1994 controls in Montreal, Canada. Lifetime alcohol consumption was elicited, by type of beverage, during in-person interviews. Odds ratios (OR) and 95% confidence intervals (CI) assessed the association between alcohol intake and PCa risk, adjusting for potential confounders and considering the subjects' PCa screening history. RESULTS: We observed a weak, non-significant positive association between high consumption of total alcohol over the lifetime and risk of high-grade PCa (OR=1.18, 95% CI 0.81-1.73). Risk estimates were more pronounced among current drinkers (OR=1.40, 95%CI 1.00-1.97), particularly after adjusting for the timing of last PCa screening (OR=1.52, 95%CI 1.07-2.16). These associations were largely driven by beer consumption. The OR for high-grade PCa associated with high beer intake was 1.37 (95%CI 1.00-1.89); it was 1.49 (95%CI 0.99-2.23) among current drinkers and 1.68 (95% CI 1.10-2.57) after adjusting for screening recency. High cumulative consumption of spirits was associated with a lower risk of low-grade PCa (OR=0.75, 95%CI 0.60-0.94) but the risk estimate no longer achieved statistical significance when restricting to current users. No association was found for wine consumption. CONCLUSION: Findings add to the accumulating evidence that high alcohol consumption increases the risk of high grade PCa. This association largely reflected beer intake in our population, and was strengthened when taking into account PCa screening history. PMID- 27664388 TI - Treatment delays, race, and outcomes in head and neck cancer. AB - PURPOSE: Patient race has been shown to predict for differences in outcomes and has been attributed to socioeconomic factors such as social support and access to healthcare. In head and neck cancer (HNC), a disease without recommended screening, we sought to investigate the association between race, treatment delays and outcome. METHODS: Records of 1802 patients with non-metastatic squamous cell HNC treated between 1998 and 2013 were retrospectively assessed from an institutional database. Patient demographics, tumor and treatment characteristics, and patient outcomes were abstracted from the chart. Differences between groups were assessed via logistic regression multivariate analysis (MVA). Outcomes including locoregional control (LRC) and overall survival (OS) were then estimated via Kaplan-Meier and Cox-regression MVA. RESULTS: Median follow up was 34 months. Patient races included white (n=1671, 93%), black (n=80, 4%), Asian (n=18, 1%), and other (n=33, 2%). On logistic regression MVA, Black patients were less likely to be married (39% vs. 63%; OR 0.5 95%CI 0.30-0.83, p=0.007) or be currently employed (43% vs. 61%; OR 0.44 95%CI 0.26-0.74, p=0.002) when compared to non-blacks. Black patients were also younger (54 vs. 59 years, p=0.001), more likely to present with advanced tumor stage (T4: 48% vs. 25%), and more often had >45days elapsed from diagnosis to treatment initiation (DTI) (61% vs. 49%, p=0.028). Delays in treatment, such as delayed diagnosis (advanced disease presentation) and delays in DTI>45days were also associated with marital and employment status. Black patients were associated with a lower 3-year LRC rate (65% vs. 81%, p<0.001) and OS rate (43% vs. 69%, p<0.001), compared to non-black patients. Patients with >45days DTI had a detriment in 3-year LRC (77% vs. 83%, p=0.002) and OS (66% vs. 69%, p=0.009). On Cox MVA, black race was independently prognostic for worse LRC (HR 1.62 95%CI 1.04-2.51, p=0.033) and OS (HR 1.55 95%CI 1.15-2.08, p=0.004) vs. non-blacks. CONCLUSION: Black race is independently prognostic for LRC and OS. Delays in HNC treatment, such as more advanced tumor stage presentation and delays in treatment initiation, may be attributed to socioeconomic factors such as employment status and social support. Efforts to accommodate these factors may expedite treatment, in hopes of improving the race related outcome disparity in HNC. PMID- 27664389 TI - Prevalence of prothrombin G20210A mutation in patients with atrial fibrillation: A systematic review and meta-analysis. PMID- 27664379 TI - Caveolins and caveolae in ocular physiology and pathophysiology. AB - Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Muller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., "lipid rafts") have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signaling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function. PMID- 27664390 TI - Transient Factor V deficiency associated with Factor V-immunoglobulin complexes but without evidence of a classical inhibitor. PMID- 27664391 TI - Early thrombin formation capacity in trauma patients and association with venous thromboembolism. AB - : Incidence of venous thromboembolism (VTE) in adult trauma patients is high despite mechanical and pharmacologic prophylaxis. We hypothesized that thrombin formation capacity as measured by calibrated automated thrombogram (CAT) is increased early in hospitalization and is associated with the development of VTE. METHODS: We conducted a prospective study in adult, critically ill trauma patients. Plasma was generated from whole blood samples collected within the first 3days of hospital admission. CAT was used to determine lag time, thrombin peak, time to thrombin peak, endogenous thrombin potential (ETP), and velocity index in plasma samples from patients, and in control samples of platelet-poor, pooled normal plasma. RESULTS: There were 35 trauma patients and 35 controls included in this pilot analysis. Patients were a mean (SD) age of 45 (19) years, and 23 (66%) were male. The most common mechanism of injury was motor vehicle crash followed by falls, and the median (IQR) injury severity score was 17 (12 27). Three patients (8.6%) had deep vein thrombosis (DVT) confirmed by Doppler ultrasound on median hospital day 7. Compared to control samples, patients had significantly longer lag times (3.1min vs. 2.7min, p=0.02) and significantly higher ETP (1136nM*min vs. 1019nM*min, p=0.007), peak thrombin generation (239nM vs. 176nM, p<0.001), and velocity index (108nM/min vs. 57nM/min, p<0.001) (Fig. 1). There was no difference in the time to peak thrombin generation between the two groups (5.5min vs. 5.7min, p=0.22). In the 3 patients with VTE compared to controls, lag times were shorter and velocity index was higher while ETP and peak thrombin generation were similar. There were no statistically significant differences in thrombin generation parameters in patients with or without VTE, but lag time was numerically shorter, and thrombin peak, time to peak and area under-the-curve (ETP) were numerically lower in patients with DVT. CONCLUSIONS: We observed a thrombin generation profile in critically ill trauma patients consistent with an early hypercoagulable state; however, thrombin generation parameters did not discriminate patients with VTE. PMID- 27664392 TI - Systemic treatment and management approaches for medullary thyroid cancer. AB - Although rare, medullary thyroid cancer (MTC) exemplifies the value that ever expanding knowledge of molecular pathways and mechanisms brings to managing challenging cancers. Although surgery can be curative for MTC in many patients, a substantial proportion of patients present with locoregional or distant metastatic disease. Once distant disease occurs, treatment options are limited, and conventional cancer treatments such as cytotoxic chemotherapy are of minimal benefit. Biomarkers such as calcitonin and carcinoembryonic antigen are important correlates of disease burden as well as predictors of disease progress, including recurrence and survival. MTC is either sporadic (~75%) or inherited (~25%) as an autosomal dominant disease. Regardless, germline and somatic mutations, particularly in the rearranged during transfection (RET) proto-oncogene, are key factors in the neoplastic process. Gain-of-function RET mutations result in overactive proteins that lead to abnormal activation of downstream signal transduction pathways, resulting in ligand-independent growth and resistance to apoptotic stimuli. Specific RET mutation variants have been found to correlate with phenotype and natural history of MTC with some defects portending a more aggressive clinical course. Greater understanding of the consequence of the aberrant signaling pathway has fostered the development of targeted therapies. Two small-molecule tyrosine kinase inhibitors, vandetanib and cabozantinib, are currently available as approved agents for the treatment of advanced or progressive MTC and provide significant increases in progression-free survival. Since there have been no head-to-head comparisons, clinicians often select between these agents on the basis of familiarity, patient characteristics, comorbidities, and toxicity profile. PMID- 27664393 TI - Improving outcomes for older women with gynaecological malignancies. AB - The incidence of most gynaecological malignancies rises significantly with increasing age. With an ageing population, the proportion of women over the age of 65 with cancer is expected to rise substantially over the next decade. Unfortunately, survival outcomes are much poorer in older patients and evidence suggests that older women with gynaecological cancers are less likely to receive current standard of care treatment options. Despite this, older women are under represented in practice changing clinical studies. The evidence for efficacy and tolerability is therefore extrapolated from a younger; often more fit population and applied to in every day clinical practice to older patients with co morbidities. There has been significant progress in the development of geriatric assessment in oncology to predict treatment outcomes and tolerability however there is still no clear evidence that undertaking a geriatric assessment improves patient outcomes. Clinical trials focusing on treating older patients are urgently required. In this review, we discuss the evidence for treatment of gynaecological cancers as well as methods of assessing older patients for therapy. Potential biomarkers of ageing are also summarised. PMID- 27664394 TI - Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy. AB - Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab. The identification of predictive and prognostic factors of survival is increasing, and both clinical predictive factors and pathology-related prognostic factors are being evaluated. Serum-based biomarkers and certain histologic subtypes of RCC, as well as clinical factors such as dose intensity and the development of some class effect adverse events, have been identified as predictors of survival. Expression levels of microRNAs, expression of chemokine receptor 4, hypermethylation of certain genes, VEGF polymorphisms, and elevation of plasma fibrinogen or d-dimer have been shown to be prognostic indicators of survival. In the future, prognosis and treatment of patients with mRCC might be based on genomic classification, especially of the 4 most commonly mutated genes in RCC (VHL, PBRM1, BAP1, and SETD2). Median overall survival has improved for patients treated with a first-line targeted agent compared with survival of patients treated with first-line interferon-alpha, and results of clinical trials have shown a survival benefit of sequential treatment with targeted agents. Prognosis of patients with mRCC will likely improve with optimization and individualization of current sequential treatment with targeted agents. PMID- 27664395 TI - Pediatric chemotherapy induced peripheral neuropathy: A systematic review of current knowledge. AB - BACKGROUND: The dramatic increase in the number of childhood cancer survivors over the last 60years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches. METHODS: Neurotoxicity data was systematically collated from Medline, Embase and Pubmed and analysed for quality, relevance and originality in three stages prior to inclusion. Quality scoring was done using the QUALSYST assessment tool. RESULTS: A total of 61 studies met inclusion criteria. Peripheral neuropathy is common and may be long lasting with characteristics specific to each chemotherapy agent. There is significant variability in reported incidence and natural history, related to challenges in clinical assessment and diagnosis. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication and patient factors such as age and inherited susceptibilities. Recent identification of individual genetic variations has advanced understanding of pathomechanisms and may direct future treatment approaches. CONCLUSION: While these studies guide suggestions for current clinical practice, further systematic research with development of strategies for amelioration and prevention of CIPN is necessary. Standardised assessment protocols and objective outcomes measures of CIPN applicable to patients of different ages are critical to enabling the development of novel treatments and facilitation of future clinical trials and treatment individualisation. PMID- 27664396 TI - [18F]JNJ42259152 binding to phosphodiesterase 10A, a key regulator of medium spiny neuron excitability, is altered in the presence of cyclic AMP. AB - Phosphodiesterase 10A (PDE10A) is a key regulator of medium spiny neuron excitability. Therefore, it plays an important role in the regulation of motor, reward, and cognitive processes. Despite the interest in PDE10A as a drug and positron emission tomography (PET) imaging target, little is known about the regulation of PDE10A enzymatic activity. This study aimed to further investigate the role of cAMP in the regulation of PDE10A activity and PDE10A PET imaging. Using [18 F]JNJ42259152 as radioligand, we investigated alterations in PDE10A binding secondary to changes in cAMP levels. An in vitro striatum homogenate binding assay was developed to determine KD and Bmax of [18 F]JNJ42259152. Homogenate binding was assessed after addition of increasing concentrations of exogenous cAMP (1, 10, and 100 MUM). Rats were treated using JNJ49137530 and rolipram to induce in vivo alterations of cAMP. The effect of the induced cAMP alterations on PDE10A binding was assessed by comparing [18 F]JNJ42259152 microPET studies after treatment to microPET studies acquired at baseline conditions prior to treatment. In vitro binding affinity of [18 F]JNJ42259152 was higher in the presence of cAMP compared to baseline conditions (KD = 3.17 +/- 0.91 nM with 10 MUM cAMP vs. KD = 6.62 +/- 0.7 nM at baseline). Inhibition of PDE4 using rolipram significantly increased [18 F]JNJ42259152 binding (BPND = 2.61 +/- 0.50 vs. 1.91 +/- 0.36 at baseline). Administration of the PDE2 inhibitor JNJ49137530 significantly increased PDE10A binding potential (BPND = 2.74 +/- 0.22 vs. 2.05 +/- 0.16 at baseline). Our data indicate an important role for cAMP in the regulation of PDE10A activity. Additionally, our data show a profound interaction between several PDEs in striatum. PMID- 27664397 TI - Unilateral hip osteoarthritis: The effect of compensation strategies and anatomic measurements on frontal plane joint loading. AB - In order to reduce pain caused by the affected hip joint, unilateral hip osteoarthritis patients (HOAP) adopt characteristic gait patterns. However, it is unknown if the knee and hip joint loading in the non-affected (limbnon-affected ) and the affected (limbaffected ) limb differ from healthy controls (HC) and which gait parameters correlate with potential abnormal joint loading. Instrumented 3D gait analysis was performed on 18 HOAP and 18 sex, age, and height matched HC. The limbnon-affected showed greater first and second peak external hip adduction moments (first HAM: +15%, p = 0.014; second HAM: +15%, p = 0.021, respectively), than seen in HC. In contrast, the second peak external knee adduction moment (KAM) in the limbaffected is reduced by about 23% and 30% compared to the limbnon affected and HC, respectively. Furthermore, our patients showed characteristic gait compensation strategies including reduced peak vertical forces (pvF), a greater foot progression angle (FPA), and reduced knee range of motion (ROM) in the limbaffected . The limbaffected was 5.6 +/- 3.8 mm shorter than the limbnon affected . Results of stepwise regression analyses showed that increased first pvF explain 16% of first HAM alterations, whereas knee ROM and FPA explain 39% of second KAM alterations. We therefore expect an increased rate of progression of OA in the hip joint of the limbnon-affected and suggest that the shift in the medial-to-lateral knee joint load distribution may impact the rate of progression of OA in the limbaffected . The level of evidence is III. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1764-1773, 2017. PMID- 27664398 TI - Efficacy and role of inulin in mitigation of enteric sulfur-containing odor in pigs. AB - BACKGROUND: The efficacy and role of inulin in the mitigation of enteric sulfur containing odor gases hydrogen sulfide (H2 S) and methyl mercaptan (CH3 SH) in pigs were examined in this study. Twelve Duroc * Landrace * Yorkshire male finisher pigs (60.7 +/- 1.9 kg), housed individually in open-circuit respiration chambers, were randomly assigned to two dietary groups, namely basal diet (control) and basal diet supplemented with 1% (w/w) inulin. At the end of the 45 day experiment, pigs were slaughtered and volatile fatty acid (VFA) concentration, sulfate radical (SO42- ) concentration, population of sulfate reducing bacteria (SRB) and expression of methionine gamma-lyase (MGL) gene were determined in contents from the caecum, colon (two segments) and rectum. Metabonomic analysis was used to compare differences in biochemical composition, and the Illumina MiSeq procedure to investigate differences in bacterial components, in the different parts of the large intestine between inulin supplemented and inulin-free (control) groups. RESULTS: Inulin decreased (P < 0.05) the average daily enteric H2 S and CH3 SH production by 12.4 and 12.1% respectively. The concentrations of acetate, propionate and butyrate in the large intestinal content were significantly increased (P < 0.05) with inulin treatment, whereas valerate concentration and MGL mRNA expression decreased (P < 0.05). The growth of Lactobacillus, Butyrivibrio, Pseudobutyrivibrio, Bifidobacterium and Clostridium butyricum was stimulated, while that of Desulfovibrio, the dominant SRB, was inhibited, and there was an accumulation of SO42- in the large intestinal content of the inulin-supplemented pigs, suggesting that inulin mitigates H2 S generation from the SO42- reduction pathway by reducing the growth of SRB. CONCLUSION: The results showed that inulin mitigates CH3 SH generation via three methionine degradation metabolic pathways and H2 S generation from two cysteine degradation metabolic pathways, thus resulting in increased synthesis of these two sulfur-containing amino acids in the pig large intestine. (c) 2016 Society of Chemical Industry. PMID- 27664400 TI - Phylogeographic past and invasive presence of Arion pest slugs in Europe. AB - Arion vulgaris (syn. A. lusitanicus) is the most destructive pest slug in Europe. The species has been regarded a classic case of an ongoing biological invasion with negative economic and ecological impact in many European countries, but this status has recently been contested. In this study, we assessed mitochondrial and autosomal genetic diversity in populations of A. vulgaris across the entire distribution range in order to characterize its evolutionary history. Mitochondrial diversity in A. vulgaris was strongly reduced compared with the closely related and largely codistributed noninvasive species A. rufus and A. ater, indicating a very rapid spread of A. vulgaris through Europe. Autosomal diversity assessed in 632 individuals from 32 populations decreased towards eastern and northern Europe which is consistent with the reported expansion of the species towards these regions in the last decades. Demographic simulations supported very recent population founding events in most of the European range. The short periods between the first detection of A. vulgaris in different countries and only a very weak association of genetic structuring among populations with geographical distances suggest a human contribution in the ongoing expansion of the slug. We propose that this contribution may ultimately prevent the exact localization of the debated region of origin of A. vulgaris. However, the reclassification of A. vulgaris as noninvasive would be premature. Without counter measures, the Eastern and Northern European countries can expect to see this biological invasion continued in the future. PMID- 27664399 TI - In silico prediction and in vitro and in vivo validation of acaricide fluazuron as a potential inhibitor of FGFR3 and a candidate anticancer drug for bladder carcinoma. AB - Bladder carcinoma (BC) is the ninth most common cause of cancer worldwide. Surgical resection and conventional chemotherapy and radiotherapy will ultimately fail due to tumor recurrence and resistance. Thus, the development of novel treatment is urgently needed. Fibroblast growth factor receptor 3 (FGFR3) is an important and well-established target for BC treatment. In this study, we utilized the free and open-source protein-ligand docking software idock to prospectively identify potential inhibitors of FGFR3 from 3,167 worldwide approved small-molecule drugs using a repositioning strategy. Six high-scoring compounds were purchased and tested in vitro. Among them, the acaricide drug fluazuron exhibited the highest antiproliferative effect in human BC cell lines RT112 and RT4. We further demonstrated that fluazuron treatment significantly increased the percentage of apoptosis cells, and decreased the phosphorylation level of FGFR3 and its downstream proteins FRS2-alpha, AKT, and ERK. We also investigated the anticancer effect of fluazuron in vivo in BALB/C nude mice subcutaneously xenografted with RT112 cells. Our results showed that oral treatment with fluazuron (80 mg/kg) significantly inhibited tumor growth. These results suggested for the first time that fluazuron is a potential inhibitor of FGFR3 and a candidate anticancer drug for the treatment of BC. PMID- 27664402 TI - Rehabilitation Trends After Lower Extremity Amputations in Canada. AB - BACKGROUND: The heterogeneity of medical complications that lead to amputation has resulted in a diverse patient population with differing rehabilitation needs; however, the rehabilitation trends for patients with lower extremity amputations across Canada have not been studied previously. OBJECTIVE: To describe trends in rehabilitation after lower extremity amputations and the factors affecting rehabilitation length of stay in Canada. DESIGN: Retrospective cohort analysis. SETTING: Canadian inpatient rehabilitation facilities that received persons with lower extremity amputations discharged from academic or community hospitals. PARTICIPANTS: Patients underwent lower extremity amputations between 2006 and 2009 for nontraumatic indications and were then discharged to a rehabilitation facility. Patients were identified from the Canadian Institute for Health Information's Discharge Abstract Database that includes hospital admissions across Canada except Quebec. INTERVENTIONS: Inpatient rehabilitation after lower extremity amputations. MAIN OUTCOME MEASURES: Length of stay, discharge destination, and change in total and motor function scores. RESULTS: The analysis included 5342 persons who underwent lower extremity amputations, 1904 of whom were transferred to a rehabilitation facility (36%). Patients most commonly underwent single below-knee (74%) and above-knee (17%) amputations. The duration of rehabilitation varied by whether the amputation was performed by a vascular (median = 36 days), orthopedic (median = 38 days), or general surgeon (median = 35 days). The overall median length of stay was 36 days. Most patients (72%) subsequently were discharged home and 9% were readmitted to hospital. Predictors of longer rehabilitation included amputation by an orthopedic surgeon (beta = 5.0, P <= .01), older age (beta = 0.2, P <= .01), and a history of ischemic heart disease (beta = 3.8, P = .03) or congestive heart failure (beta = 5, P = .04). Patients who spent <7 days in hospital were significantly more likely to have a shorter rehabilitation stay (beta = -4, P = .03). Advanced patient age was the only predictor for hospital readmission (odds ratio = 1.03, P <= .01). CONCLUSIONS: Rehabilitation length of stay in Canada after lower extremity amputation varies by the type of surgeon performing the amputation. Advanced age, undergoing surgery in the province of Manitoba, and having a history of ischemic heart disease or congestive heart failure predict a longer rehabilitation stay. A shorter perioperative hospitalization period (<7 days) predicts a shorter rehabilitation duration. Future studies are needed to explore these issues and to optimize the delivery of rehabilitation services to Canadians after lower extremity amputation. LEVEL OF EVIDENCE: II. PMID- 27664401 TI - Prioritizing Systemic Corticosteroid Treatments to Mitigate Relapse in Adults With Acute Asthma: A Systematic Review and Network Meta-analysis. AB - OBJECTIVES: While systemic corticosteroids (SCS) are widely used to prevent relapse in adults with acute asthma discharged from the emergency department, the most effective route of administration is unclear. The objective of this review was to examine the effectiveness of SCS in adults and to identify the most effective route of SCS to preventing relapse. METHODS: A search was conducted to identify randomized controlled trials comparing the effectiveness of intramuscular (IM) or oral (PO) short-course or long-course corticosteroids to prevent relapse in adults with acute asthma. Two independent reviewers judged study relevance, inclusion, and risk of bias. Pooled statistics were calculated as risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CI) and credibility intervals (CrI) using a random-effects model. A Bayesian network meta analysis was performed for indirect comparisons of SCS to placebo. Probability of best (PB) analysis was reported for comparisons between the routes of administration. RESULTS: Thirteen studies of moderate quality were included. Four studies compared SCS to placebo, in which SCS significantly reduced relapse (RR = 0.43; 95% CI = 0.25 to 0.74). In the network meta-analysis, a significant reduction in relapse within 10 days of discharge was found in adults receiving IM (OR = 0.21; 95% CrI = 0.05 to 0.73) and PO long-course (OR = 0.31; 95% CrI = 0.09 to 0.95) corticosteroids. Relapse rates between PO short-course corticosteroids and placebo were not statistically significantly different (OR = 0.37; 95% CrI = 0.04 to 3.38). PB analysis favored IM corticosteroids (62%) followed by PO short course (20.3%) and PO long-course (14.1%) corticosteroids. CONCLUSIONS: The network analysis identified IM corticosteroids and PO long-course corticosteroids as the most effective strategies to prevent relapse among adults with acute asthma, compared to PO short-course corticosteroids. The lack of significant findings with PO short-course corticosteroids is likely due to the paucity of research. Further comparative studies are required to determine the safety and effectiveness of briefer PO SCS treatment options in adults. PMID- 27664403 TI - Evaluating the Functionality and Usability of Two Novel Wheelchair Anti-Rollback Devices for Ramp Ascent in Manual Wheelchair Users With Spinal Cord Injury. AB - BACKGROUND: Difficulty ascending ramps and inclines with a manual wheelchair adversely affects the everyday mobility and overall quality of life of manual wheelchair users. Currently, various anti-rollback devices are available to assist manual wheelchair users to ascend ramps and inclines. However, these devices have 2 main shortcomings: restriction to backward motion limiting recovery from an overturning wheelchair, which is a safety concern; and difficulty in engaging/disengaging the device while on the ramp. OBJECTIVE: To evaluate the functionality and usability of 2 novel wheelchair anti-rollback devices developed to address these shortcomings (prototypes "Wheel" and "Brake"). DESIGN: Cross-sectional. SETTING: Rehabilitation research facility. PARTICIPANTS: Twelve adult participants with chronic spinal cord injury. METHODS: Participants completed training and tested with both the wheelchair anti-rollback devices on a 7.3-m-long ramp. MAIN OUTCOME MEASUREMENTS: Number of stops, perceived physical exertion, pain, and ease of use of these devices as participants maneuvered their wheelchairs up a 7.3-m ramp were assessed. Participants also evaluated their satisfaction with the usability of both the devices using the Quebec User Evaluation of Satisfaction With Assistive Technology (QUEST 2.0). RESULTS: Both prototypes evaluated overcame the limitations of the existing anti-rollback devices. Nonparametric statistical tests showed that participants rated both prototypes similarly for the overall functional and usability aspects. However, the participants' satisfactory rating were higher for the prototype "Brake" than for the prototype "Wheel" based on a functional aspect (ie, engaging/disengaging easiness), and higher for Wheel than for Brake, based on a usability aspect (prototype size). CONCLUSIONS: The qualitative and quantitative outcomes of this investigation, based on the usability and functional evaluations, provided useful information for the improvement in the design of both anti-rollback devices, which may allow manual wheelchair users to manage ramp ascent more safely and easily. Further evaluations with a different SCI population is recommended. LEVEL OF EVIDENCE: IV. PMID- 27664404 TI - The Craig Hospital Eye Evaluation Rating Scale (CHEERS). AB - BACKGROUND: Oculomotor deficits in smooth pursuit, saccades, vestibular-ocular reflex (VOR), vergence, and fixation are common problems seen after moderate to severe traumatic brain injury (TBI). No scale currently exists to rate all of these together. The Craig Hospital Eye Evaluation Rating Scale (CHEERS) was designed to systematically quantify frequency and severity of eye movement deficits in TBI. OBJECTIVE: To assess the intra- and interrater reliability of a new rating scale for detecting the presence and degree of 5 oculomotor abnormalities after TBI. DESIGN: A reliability study. SETTING: This was an institution-based study at Craig Rehabilitation Hospital. PARTICIPANTS: English speaking patients between ages 18 and 65 years with a primary diagnosis of moderate to severe mechanical TBI and who were not blind in either eye were eligible. METHODS: Between October 2013 and March 2014, a total of 11 TBI patients and 9 non-TBI controls were enrolled in the study. The median age was 30 years (range, 18-74 years) for subjects and 52 years (range, 28-63 years) for controls. All patients were male, and 8 of 9 controls were female. Eye movements (fixation, smooth pursuit, saccade, convergence, and vestibular-ocular reflex) were recorded for each on digital video. They were rated on 2 separate occasions by each of the 2 raters. MAIN OUTCOME MEASUREMENTS: Inter- and intrarater reliability tests. RESULTS: Median elapsed time between the first and second ratings was 7 days (range, 5-44 days). Intrarater agreement was very strong (Spearman rho >= 0.900) for pursuit, saccades, and VOR for both raters, and strong (Spearman rho >= 0.710) for vergence and fixation. The interrater agreement for detecting presence of any oculomotor abnormality was substantial (unweighted kappa = 0.63). The interrater concordance on the full range of scale scoring was strongest on the VOR test (weighted kappa = 0.98), was substantial for vergence, pursuit, saccades, and total score (weighted kappa > 0.60), and was moderate for fixation. For TBI patients, every eye movement rated was found to be more abnormal than compared to those in the controls. CONCLUSIONS: CHEERS is a reliable scale for assessing and quantifying oculomotor deficits commonly observed in moderate to severe TBI. Further studies to validate the scale's utility in outcome prediction, and its applicability to broader brain injury populations, are warranted. LEVEL OF EVIDENCE: IV. PMID- 27664405 TI - Activity Limitation Stages Are Associated With Risk of Hospitalization Among Medicare Beneficiaries. AB - BACKGROUND: Activity limitation stages based on activities of daily living (ADLs) and instrumental activities of daily living (IADLs) are associated with 3-year mortality in elderly Medicare beneficiaries, yet their associations with hospitalization risk in this population have not been studied. OBJECTIVE: To examine the independent association of activity limitation stages with risk of hospitalization within a year among Medicare beneficiaries aged 65 years and older. DESIGN: Cohort study. SETTING: Community. PARTICIPANTS: A total of 9447 community-dwelling elderly Medicare beneficiaries from the Medicare Current Beneficiary Survey for years 2005-2009. METHODS: Stages were derived for ADLs and IADLs separately. Associations of stages with time to first hospitalization and time to recurrent hospitalizations within a year were assessed with Cox proportional hazards models, with which we accounted for baseline sociodemographics, smoking status, comorbidities, and the year of survey entry. MAIN OUTCOMES: Time to first hospitalization and time to recurrent hospitalizations within 1 year. PRINCIPLE FINDINGS: The adjusted risk of first hospitalization increased with greater activity limitation stages (except stage III). The hazard ratios (95% confidence intervals) for ADL stages I-IV compared with stage 0 (no limitations) were 1.49 (1.36-1.63), 1.61 (1.44-1.80), 1.54 (1.35 1.76), and 2.06 (1.61-2.63), respectively. The pattern for IADL stages was similar. For recurrent hospitalizations, activity limitation stages were associated with the risk of the first hospitalization but not with subsequent hospitalizations. CONCLUSION: Activity limitation stages are associated with the risk of first hospitalization in the subsequent year among elderly Medicare beneficiaries. Stages capture clinically interpretable profiles of ADL and IADL functionality and describe preserved functions and activity limitation in an aggregated measure. Stage can inform interventions to ameliorate disability and thus reduce the risk of a subsequent hospitalization in this population. LEVEL OF EVIDENCE: IV. PMID- 27664406 TI - Nonadherence to psoriasis medication as an outcome of limited coping resources and conflicting goals: findings from a qualitative interview study with people with psoriasis. AB - BACKGROUND: Medication nonadherence is known to limit the effectiveness of available therapies; however, little is known specifically about medication adherence in people with psoriasis. Medicines self-management can feel onerous to those with dermatological conditions due to the nature of therapies prescribed and many individuals with psoriasis experience additional challenges such as physical and psychological comorbidities that place significant additional demands on individuals and may undermine adherence. Viewing nonadherence to medication as an outcome of limited personal coping resources and conflicting goals may help to explain medication nonadherence. OBJECTIVES: To explore individuals' perspectives of their psoriasis, medication and its management. METHODS: Twenty people with psoriasis were recruited from community samples in England and interviewed in-depth about their perceptions of their psoriasis, medication, and adherence to medication and self-management advice. Data were analysed using Framework Analysis. RESULTS: Participants reported that adhering to recommended treatment regimens conflicted with the management of the physical and psychological demands of living with psoriasis. Medication usage was viewed as a source of unresolved emotional distress and, for some, resulted in poor self reported adherence, which included medication overuse, underuse and rejection of prescribed therapies. Perceived lack of engagement by clinicians with participants' self-management difficulties was viewed as an additional source of stress and distress. CONCLUSIONS: Adhering to medication in psoriasis can be an additional source of considerable emotional distress. We interpreted some episodes of nonadherence to psoriasis medication as rational attempts by individuals to minimize distress and to gain control over their life. PMID- 27664408 TI - Selenocysteine detection and bioimaging in living cells by a colorimetric and near-infrared fluorescent turn-on probe with a large stokes shift. AB - Selenocysteine (Sec) has emerged as an important sensing target in recent years. In this paper, a colorimetric and near-infrared fluorescent turn-on probe for Sec was developed. This probe features a remarkable large Stokes shift (146nm) and shows a rapid, highly selective detection process for Sec with obvious colorimetric and near-infrared fluorescent (Em 706nm with Ex 560nm) turn-on responses. In addition, this probe can be used to quantitatively detect Sec with high sensitivity with a detection limit of 62nM over a wide linear range (0.2 80MUM). Moreover, it was further demonstrated that this NIR fluorescent probe can be employed to image both exogenous and endogenous Sec in living cells, indicating that this probe has great potential for biological applications. PMID- 27664407 TI - Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection. AB - Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of l-carnitine, a substance involved in the transport of fatty acids into mitochondria. JFH-1 or HCV replicon transfected Huh7.5.1 cells were treated with or without l-carnitine to examine its anti-HCV effects. The effects of l-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined. Treatment of JFH-1-infected cells with l-carnitine inhibited HCV propagation in a concentration-dependent manner. In contrast, l-carnitine had no anti-HCV activity in the HCV replicon system, which is lacking viral assembly. In addition, l-carnitine did not affect HCV entry. However, l-carnitine treatment decreased intracellular lipid droplets, which are crucial for HCV assembly in JFH 1-infected cells. The expression level of CPT-1 was decreased in JFH-1-infected cells, and l-carnitine treatment restored this expression. HCV-infected cells exhibited increased production of reactive oxygen species and glutathione oxidation. l-carnitine decreased oxidative stress induced by JFH-1-infection, as shown by glutathione/glutathione disulfide assays and MitoSOX staining. l carnitine exhibited anti-HCV activity, possibly by inhibiting HCV assembly and through its anti-adipogenic activity in HCV-infected cells. Moreover, l-carnitine has antioxidant properties in HCV-infected hepatocytes. Overall, these results indicated that l-carnitine may be an effective adjunctive agent in antiviral therapies to treat chronic hepatitis C. J. Med. Virol. 89:857-866, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27664409 TI - A portable and multiplexed bioelectronic sensor using human olfactory and taste receptors. AB - A multiplexed bioelectronic sensor was developed for the purpose of rapid, on site, and simultaneous detection of various target molecules. Olfactory and taste receptors were produced in Escherichia coli, and the reconstituted receptors were immobilized onto a multi-channel type carbon nanotube field-effect transistor. This device mimicked the human olfactory/taste system and simultaneously measured the conductance changes with high sensitivity and selectivity following treatment with various odor and taste molecules commonly known to be indicators of food contamination. Various pattern recognition of odorants and tastants was available with a customized platform for the simultaneous measurement of electrical signals. The simple portable bioelectronic device was suitable for efficient monitoring of food freshness and is expected to be used as a rapid on-site sensing platform with various applications. PMID- 27664411 TI - High-throughput identification of telomere-binding ligands based on the fluorescence regulation of DNA-copper nanoparticles. AB - Formation of the G-quadruplex in the human telomeric DNA is an effective way to inhibit telomerase activity. Therefore, screening ligands of G-quadruplex has potential applications in the treatment of cancer by inhibit telomerase activity. Although several techniques have been explored for screening of telomeric G quadruplexes ligands, high-throughput screening method for fast screening telomere-binding ligands from the large compound library is still urgently needed. Herein, a label-free fluorescence strategy has been proposed for high throughput screening telomere-binding ligands by using DNA-copper nanoparticles (DNA-CuNPs) as a signal probe. In the absence of ligands, human telomeric DNA (GDNA) hybridized with its complementary DNA (cDNA) to form double stranded DNA (dsDNA) which can act as an efficient template for the formation of DNA-CuNPs, leading to the high fluorescence of DNA-CuNPs. In the presence of ligands, GDNA folded into G-quadruplex. Single-strdanded cDNA does not support the formation of DNA-CuNP, resulting in low fluorescence of DNA-CuNPs. Therefore, telomere-binding ligands can be high-throughput screened by monitoring the change in the fluorescence of DNA-CuNPs. Thirteen traditional chinese medicines were screened. Circular dichroism (CD) measurements demonstrated that the selected ligands could induce single-stranded telomeric DNA to form G-quadruplex. The telomere repeat amplification protocol (TRAP) assay demonstrated that the selected ligands can effectively inhibit telomerase activity. Therefore, it offers a cost-effective, label-free and reliable high-throughput way to identify G-quadruplex ligands, which holds great potential in discovering telomerase-targeted anticancer drugs. PMID- 27664410 TI - Multiplexed immunochromatographic test strip for time-resolved chemiluminescent detection of pesticide residues using a bifunctional antibody. AB - A novel bifunctional antibody (BfAb) that could recognize methyl parathion and imidacloprid simultaneously was prepared by a hybrid hybridomas technique. Using the BfAb as the sole recognition reagent, a multiplexed immunochromatographic test strip based on a time-resolved chemiluminescence (CL) strategy was developed for quantitative detection of pesticide residues. Horseradish peroxidase (HRP) and alkaline phosphatase (ALP) were used as the CL probes to label the haptens of methyl parathion and imidacloprid, respectively. After the labeled haptens competed with methyl parathion and imidacloprid to bind with the BfAb immobilized on the test strip, the two CL reactions catalyzed by the enzymes were triggered simultaneously by coreactants injection. Due to the distinct CL kinetics characteristics of HRP and ALP, the signals for methyl parathion and imidacloprid detections were collected at 2.5s and 300s, respectively. The linear ranges for methyl parathion and imidacloprid were both 0.1-250ngmL-1, with detection limits of 0.058ngmL-1 (S/N=3). The whole assay process could be accomplished within 22min. The detection results for spiked traditional Chinese medicine samples demonstrated its application potential. The proposed method provided a low-cost, facile and rapid tool for multiplexed screening of pesticide residues using single antibody. PMID- 27664412 TI - Rapid biosensing tools for cancer biomarkers. AB - The present review critically discusses the latest developments in the field of smart diagnostic systems for cancer biomarkers. A wide coverage of recent biosensing approaches involving aptamers, enzymes, DNA probes, fluorescent probes, interacting proteins and antibodies in vicinity to transducers such as electrochemical, optical and piezoelectric is presented. Recent advanced developments in biosensing approaches for cancer biomarker owes much credit to functionalized nanomaterials due to their unique opto-electronic properties and enhanced surface to volume ratio. Biosensing methods for a plenty of cancer biomarkers has been summarized emphasizing the key principles involved. PMID- 27664413 TI - Quantum dots-labeled strip biosensor for rapid and sensitive detection of microRNA based on target-recycled nonenzymatic amplification strategy. AB - MicroRNAs (miRNAs) have been proved to be potential biomarkers in early cancer diagnosis. It is of great significance for rapid and sensitive detection of miRNAs, particularly with point-of-care (POC) diagnosis. Herein, it is the first time to construct quantum dots (QDs)-labeled strip biosensor based on target recycled nonenzymatic amplification strategy for miRNA detection. In the system, QDs were served as bright, photostable signal labels, which endow this biosensor with good detection efficiency. Moreover, a target-recycled amplification strategy relies on sequence-specific hairpins strand displacement process without the assistance of enzymes, was introduced to further improve the sensitivity. Meanwhile eliminating the requirement of environment-susceptible enzyme protein makes it easy to preserve and enhances the stability and reproducibility of this sensor. Benefiting from these outstanding characteristics, this platform exhibited a good detection sensitivity range from 2fmol to 200fmol with a limit of 200amol, using only 20MUL of sample within 80min. The assay was also 10-fold more sensitive than that with a conventional colloidal gold-based test strip for miRNA detection. Additionally, the analysis of miRNA in various tumor cell extracts was in accordance with the performance of quantitative realtime polymerase chain reaction (qRT-PCR). Clinical tumor samples were also tested, and 16 of 20 samples gave out positive signals, which demonstrated the practical application capacity of the biosensor. Therefore, the proposed biosensor holds great promise for potential POC applications and early cancer diagnosis. PMID- 27664414 TI - PCOS remains a diagnosis of exclusion: a concise review of key endocrinopathies to exclude. AB - Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS. PMID- 27664415 TI - Abnormal vocal cord movement in patients with and without airway obstruction and asthma symptoms. AB - BACKGROUND: Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called vocal cord dysfunction - VCD) leading to asthma like symptoms. These aberrant movements are characteristically present during inspiration and termed paradoxical vocal cord movement (PVCM). We have reported PVCM in up to 40% of severe asthmatics, but it is not known if PVCM is detectable in all patients with asthma-like symptoms and if the condition is more often associated with abnormal lung function. OBJECTIVE: We hypothesized that PVCM is frequently associated with asthma symptoms accompanied by airflow limitation. Studies examined whether PVCM is solely linked to experiencing asthma symptoms, or if PVCM is related to airflow limitation and/or other disease characteristics. METHODS: Patients with asthma symptoms were recruited from general practice and severe asthma clinics (n = 155). Pulmonary function measurements were conducted, asthma control and Nijmegen (dysfunctional breathing) questionnaires were administered and skin prick testing was carried out. PVCM was quantified using dynamic 320-slice computerized tomography of the larynx. Groups were divided into patients with FEV1 >= 80% predicted or FEV1 < 80% predicted and FEV1 /FVC < 0.7. ATS/ERS definitions of severity were also applied and evaluated. Detection of PVCM in the groups was compared and analyses performed to identify features associated with PVCM. RESULTS: Overall (n = 155), PVCM was detected in 42 cases (27.1%). Patients with FEV1 < 80% predicted had PVCM more often (25/68, 36.8%) than individuals with normal spirometry (17/87, 19.5%; P = 0.016). PVCM was associated with older age (P = 0.003) and with Nijmegen scores > 20 (P = 0.04). Patients with FEV1 < 80% predicted plus Nijmegen scores > 20 were more likely to have PVCM (OR = 9.3, P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Paradoxical vocal cord movement is more often associated with asthma symptoms accompanied by airflow limitation and dysfunctional breathing. Further studies are needed to determine whether PVCM is induced by dysfunctional breathing practices and/or airway obstruction. How PVCM links with symptomatic asthma and VCD also requires evaluation. PMID- 27664416 TI - Cerebrospinal fluid dynamics at the lumbosacral level in patients with spinal stenosis: A pilot study. AB - Spinal stenosis is a common degenerative condition. However, how neurogenic claudication develops has not been clearly elucidated. Moreover, cerebrospinal fluid physiology at the lumbosacral level has not received adequate attention. This study was conducted to compare cerebrospinal fluid hydrodynamics at the lumbosacral spinal level between patients with spinal stenosis and healthy controls. Twelve subjects (four patients and eight healthy controls; 25-77 years old; seven males) underwent phase-contrast magnetic resonance imaging to quantify cerebrospinal fluid dynamics. The cerebrospinal fluid flow velocities were measured at the L2 and S1 levels. All subjects were evaluated at rest and after walking (to provoke neurogenic claudication in the patients). The caudal peak flow velocity in the sacral spine (-0.25 +/- 0.28 cm/s) was attenuated compared to that in the lumbar spine (-0.93 +/- 0.46 cm/s) in both patients and controls. The lumbar caudal peak flow velocity was slower in patients (-0.65 +/- 0.22 cm/s) than controls (-1.07 +/- 0.49 cm/s) and this difference became more pronounced after walking (-0.66 +/- 0.37 cm/s in patients, -1.35 +/- 0.52 cm/s in controls; p = 0.028). The sacral cerebrospinal fluid flow after walking was barely detectable in patients (caudal peak flow velocity: -0.09 +/- 0.03 cm/s). Cerebrospinal fluid dynamics in the lumbosacral spine were more attenuated in patients with spinal stenosis than healthy controls. After walking, the patients experiencing claudication did not exhibit an increase in the cerebrospinal fluid flow rate as the controls did. Altered cerebrospinal fluid dynamics may partially explain the pathophysiology of spinal stenosis. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:104-112, 2017. PMID- 27664418 TI - Chronic Stress and Negative Marital Quality Among Older Couples: Associations With Waist Circumference. AB - OBJECTIVE: More than a third of the U.S. population of older adults is obese. The present study tests the Dyadic Biopsychosocial Model of Marriage and Health, which hypothesizes that, among married couples, individual and partner chronic stress predicts increased waist circumference and these links are exacerbated in negative quality marriages. METHOD: Participants were from the nationally representative longitudinal Health and Retirement Study (HRS). A total of 2,042 married individuals (in 1,098 married couples) completed psychosocial and waist circumference assessments in 2006 and 2010. Analyses examined whether negative marital quality and chronic stress in Wave 1 (2006) were associated with changes in waist circumference over time. RESULTS: Actor-partner interdependence models revealed that greater partner stress, rather than individuals' own reports of stress, was associated with increased waist circumference over time. Higher perceived negative marital quality among husbands and lower negative marital quality among wives exacerbated the positive link between partner stress and waist circumference. DISCUSSION: Consistent with the Dyadic Biopsychosocial Model of Marriage and Health, partner stress has direct associations with waist circumference among couples and this link is moderated by negative marital quality. Thus, dyadic perceptions of stress and negative marital quality are important to consider for understanding marriage and obesity. PMID- 27664419 TI - Bacterial flagellar capping proteins adopt diverse oligomeric states. AB - Flagella are crucial for bacterial motility and pathogenesis. The flagellar capping protein (FliD) regulates filament assembly by chaperoning and sorting flagellin (FliC) proteins after they traverse the hollow filament and exit the growing flagellum tip. In the absence of FliD, flagella are not formed, resulting in impaired motility and infectivity. Here, we report the 2.2 A resolution X-ray crystal structure of FliD from Pseudomonas aeruginosa, the first high-resolution structure of any FliD protein from any bacterium. Using this evidence in combination with a multitude of biophysical and functional analyses, we find that Pseudomonas FliD exhibits unexpected structural similarity to other flagellar proteins at the domain level, adopts a unique hexameric oligomeric state, and depends on flexible determinants for oligomerization. Considering that the flagellin filaments on which FliD oligomers are affixed vary in protofilament number between bacteria, our results suggest that FliD oligomer stoichiometries vary across bacteria to complement their filament assemblies. PMID- 27664420 TI - Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export. AB - LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon's disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression improves tissue function in models of aging. We show here that human LAMP1 and LAMP2 bind cholesterol in a manner that buries the cholesterol 3beta hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lysosomes. Quantitation of cellular LAMP2 and NPC1 protein levels suggest that LAMP proteins represent a significant cholesterol binding site at the lysosome limiting membrane, and may signal cholesterol availability. Functional rescue experiments show that the ability of human LAMP2 to facilitate cholesterol export from lysosomes relies on its ability to bind cholesterol directly. PMID- 27664421 TI - Upregulation of neurovascular communication through filamin abrogation promotes ectopic periventricular neurogenesis. AB - Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs' neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs. We show that by collaborating with beta-arrestin, Flna maintains the homeostatic signaling between the vasculature and NPCs, and loss of this function results in escalated Vegfa and Igf2 signaling, which exacerbates both EMT and angiogenesis to further potentiate IPs' neurogenesis. These results suggest that the neurogenic potential of IPs may be boosted in vivo by manipulating Flna-mediated neurovascular communication. PMID- 27664422 TI - Editor's Highlight: Screening ToxCast Prioritized Chemicals for PPARG Function in a Human Adipose-Derived Stem Cell Model of Adipogenesis. AB - The developmental origins of obesity hypothesis posits a multifaceted contribution of factors to the fetal origins of obesity and metabolic disease. Adipocyte hyperplasia in gestation and early childhood may result in predisposition for obesity later in life. Rodent in vitro and in vivo studies indicate that some chemicals may directly affect adipose progenitor cell differentiation, but the human relevance of these findings is unclear. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARG) is the master regulator of adipogenesis. Human adipose-derived stem cells (hASC) isolated from adipose tissue express endogenous isoforms of PPARG and represent a biologically relevant cell-type for evaluating activity of PPARG ligands. Here, a multi-endpoint approach based on a phenotypic adipogenesis assay was applied to screen a set of 60 chemical compounds identified in ToxCast Phase I as PPARG active (49) or inactive (11). Chemicals showing activity in the adipogenesis screen were further evaluated in a series of 4 orthogonal assays representing 7 different key events in PPARG-dependent adipogenesis, including gene transcription, protein expression, and adipokine secretion. An siRNA screen was also used to evaluate PPARG-dependence of the adipogenesis phenotype. A universal concentration-response design enabled inter-assay comparability and implementation of a weight-of-evidence approach for bioactivity classification. Collectively, a total of 14/49 (29%) prioritized chemicals were identified with moderate-to-strong activity for human adipogenesis. These results provide the first integrated screening approach of prioritized ToxCast chemicals in a human stem cell model of adipogenesis and provide insight into the capacity of PPARG activating chemicals to modulate early life programming of adipose tissue. PMID- 27664423 TI - From the Cover: PhIP/DSS-Induced Colon Carcinogenesis in CYP1A-Humanized Mice and the Possible Role of Lgr5+ Stem Cells. AB - In the past decades, experimental rodent models developed to study the pathogenesis of human colorectal cancer (CRC) generally employed synthetic chemical carcinogens or genetic manipulation. Our lab, in order to establish a more physiologically relevant CRC model, recently developed a colon carcinogenesis model induced by the meat-derived dietary carcinogen, 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and promoted by dextran sodium sulfate (DSS)-induced colitis in the cytochrome P450 1A-humanized (hCYP1A) mice. The resulting colon tumors shared many histologic and molecular features of human colon cancer. In this study, we characterized the early stages of PhIP/DSS induced colon carcinogenesis. We found that PhIP/DSS treatments caused rapid destruction of the colon mucosa with severe inflammation, followed by the presence of reactive changes and low-grade dysplastic lesions, and then manifestation of high-grade dysplastic lesions and finally adenocarcinomas. Molecular analysis of the early time-points (ie, days 1, 3, 7, 11, 14, and 21 after DSS exposure) indicates Ctnnb1/beta-catenin mutations and beta-catenin nuclear accumulation in the high-grade dysplastic lesions, but not low-grade dysplastic lesions or adjacent normal tissues. In addition, we investigated the role of Lgr5+ colon stem cells in the PhIP/DSS-induced colon carcinogenesis and found the presence of Lgr5-enhance green fluorescent protein-expressing cells amidst some ulcerated mucosa, high-grade dysplastic lesions and adenocarcinomas, suggesting a possible role of Lgr5+ stem cells in this dietary carcinogen induced, inflammation-promoted colon carcinogenesis model. Overall, the findings suggest that PhIP/DSS-induced colon carcinogenesis is likely initiated by dominant active Ctnnb1/beta-catenin mutation in residual epithelial cells, which when promoted by colitis, developed into high-grade dysplasia and adenocarcinoma. PMID- 27664425 TI - Can mitomycin facilitate endoscopic dilatation treatment of benign oesophageal stricture? AB - A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Can mitomycin facilitate endoscopic dilatation treatment of benign esophageal stricture (mainly including caustic and anastomotic esophageal stricture)?' Altogether, 115 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question, which included 1 randomized controlled trial, 1 systematic review and 4 cohort studies. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Mytomicin was topically applied as an adjunct to endoscopic dilatation with a concentration of 0.1-1 mg/ml in those included studies. Most of the studies reported that topical application of mitomycin could augment the effect of endoscopic dilatation treatment to achieve less dilatation number and significant improvement of dysphagia in patients suffering benign oesophageal stricture, and would not increase the risk of complications. These satisfying adjunct effects were observed in both child patients and adult patients. Therefore, we conclude that mitomycin can serve as a useful adjunct to endoscopic dilatation for benign oesophageal stricture. On the basis of our evidence, we strongly believe that topical application of mitomycin would augment the efficacy of endoscopic dilatation of benign oesophageal stricture. PMID- 27664424 TI - Pooled analysis for surgical treatment for isolated adrenal metastasis and non small cell lung cancer. AB - OBJECTIVES: This systematic review and pooled analysis investigated outcomes and prognostic factors in Non-small-cell lung cancer (NSCLC) patients who underwent surgical treatment for an isolated adrenal metastasis and the primary NSCLC. METHODS: A literature search of PubMed, Embase and Cochrane Library databases was conducted for relevant retrospective studies in patients with NSCLC and isolated adrenal metastatic lesions treated with lobectomy or pneumonectomy and adrenalectomy. Outcome measures were overall, 1-, 2- and 5-year survival rates stratified by synchronous versus metachronous adrenal metastasis and according to lymph node status, pathology and relative location of the metastasis to the primary tumour. Kaplan-Meier survival curves were generated and differences in survival were assessed by a log-rank test. RESULTS: Thirteen studies involving 98 patients were included in this analysis. The median overall survival was 18 months, and the 1-, 2- and 5-year survival rates were 66.5, 40.5 and 28.2%, respectively. Patients with metachronous adrenal metastasis had a significantly better prognosis than patients with synchronous adrenal metastasis (P < 0.05). Patients classified as negative for lymph node metastasis had a significantly better prognosis than patients classified as positive for lymph node metastasis (P < 0.05). Pathology (squamous carcinoma versus adenocarcinoma) and the relative location of the metastasis to the primary tumour (ipsilateral adrenal metastasis or contralateral adrenal metastasis) had no significant influence on prognosis. CONCLUSIONS: NSCLC patients with isolated adrenal metastasis undergoing surgical treatment for the primary tumour and adrenal metastasis could achieve a significant survival benefit, especially if they have metachronous adrenal metastasis or are negative for lymph node metastasis. PMID- 27664426 TI - The totally thoracoscopic maze procedure for the treatment of atrial fibrillation. AB - The purpose of this study was to update the current evidence regarding the efficacy and safety of the totally thoracoscopic maze (TT-maze) procedure for the treatment of atrial fibrillation (AF). Fourteen studies published between 2011 and 2016 and comprising 1171 patients were included as follows: 545 (46%) patients had paroxysmal AF (pAF), 268 (23%) persistent AF (persAF) and 358 (31%) longstanding persistent AF (LSPAF). Fixed- and random-effect models were used to calculate the pooled overall freedom from atrial arrhythmias. The 1- and 2-year pooled overall antiarrhythmic drug (AAD) free (off-AAD) success rates were 78% (95% confidence interval (CI): 72-83%, n = 13) and 77% (95% CI: 64-86%, n = 6), respectively. The 1- and 2-year pooled on-AAD success rates were 84% (95% CI: 78 89%, n = 5) and 85% (95% CI: 78-90%, n = 3), respectively. Subanalysis regarding the different types of AF revealed a 1-year pooled off-AAD success rate of 81% (95% CI: 73-86%, n = 7) for pAF, 63% (95% CI: 57-69%, n = 5) for persAF and 67% (95% CI: 52-79%, n = 3) for LSPAF. The overall in-hospital complication rate was <3% (n = 36). We conclude that the TT-maze is an effective strategy for the treatment of AF with maintained efficacy at the 2-year follow-up. Furthermore, the TT-maze has demonstrated similar efficacy to the Cox Maze IV procedure at the midterm follow-up with a lower complication rate. Extended follow-up research is needed to determine whether the high success rates after TT-maze will be stable over time. PMID- 27664427 TI - Is the Ross procedure a riskier operation? Perioperative outcome comparison with mechanical aortic valve replacement in a propensity-matched cohort. AB - OBJECTIVES: The aim of this study was to compare perioperative outcomes in young adults following isolated Ross procedure versus mechanical aortic valve replacement (AVR) in a high-volume centre. METHODS: From 2007 to 2015, 337 elective isolated mechanical AVRs and 137 Ross procedures were performed in young adults (<65 years) at our centre. Using a 1:1 propensity score match analysis, 140 patients were included in the study (n = 70 in each group). Perioperative outcomes were defined using STS guidelines. The primary outcome was operative mortality. RESULTS: Median age was 52 [14] years and EuroSCORE II was 1.0 [0.4]%. There were no mortalities in the two groups. There were no differences in the incidence of myocardial injury (0% overall) and neurological complications (0.7% overall). Three (4%) reinterventions for bleeding were required in the Ross cohort versus six (9%) in the mechanical AVR cohort (P = 0.49). A significant increase in serum creatinine (>2-fold increase) was more commonly observed after the Ross procedure (11 vs 1%; P = 0.03), but there was no significant difference in the rate of temporary dialysis. Twenty-seven patients (39%) required >=1 blood product transfusion in the Ross group, whereas 21 patients (31%) did so in the mechanical AVR group (P = 0.47). Median hospital length of stay was similar in both the groups (6 days). CONCLUSIONS: There are no differences in mortality or major perioperative outcomes in adults undergoing an isolated Ross procedure or mechanical AVR. PMID- 27664428 TI - Influence of lead apron shielding on absorbed doses from cone-beam computed tomography. AB - The aim of the present work was to investigate absorbed and to calculate effective doses (EDs) in cone-beam computed tomography (CBCT). The study was conducted using examination protocols with and without lead apron shielding. A full-body male RANDO(r) phantom was loaded with 110 GR200A thermoluminescence dosemeter chips at 55 different sites and set up in two different CBCT systems (CS 9500(r), ProMax(r) 3D). Two different protocols were performed: the phantom was set up (1) with and (2) without a lead apron. No statistically significant differences in organ and absorbed doses from regions outside the primary beam could be found when comparing results from exposures with and without lead apron shielding. Consequently, calculating the ED showed no significant differences between the examination protocols with and without lead apron shielding. For the ProMax(r) 3D with shielding, the ED was 149 uSv, and for the examination protocol without shielding 148 uSv (SD = 0.31 uSv). For the CS 9500(r), the ED was 88 and 86 uSv (SD = 0.95 uSv), respectively, with and without lead apron shielding. The results revealed no statistically significant differences in the absorbed doses between examination with and without lead apron shielding, especially in organs outside the primary beam. PMID- 27664429 TI - Conversion Coefficients for Proton Beams using Standing and Sitting Male Hybrid Computational Phantom Calculated in Idealized Irradiation Geometries. AB - The aim of this study was the calculation of conversion coefficients for absorbed doses per fluence (DT/Phi) using the sitting and standing male hybrid phantom (UFH/NCI) exposure to monoenergetic protons with energy ranging from 2 MeV to 10 GeV. Sex-averaged effective dose per fluence (E/Phi) using the results of DT/Phi for the male and female hybrid phantom in standing and sitting postures were also calculated. Results of E/Phi of UFH/NCI standing phantom were also compared with tabulated effective dose conversion coefficients provided in ICRP publication 116. To develop an exposure scenario implementing the male UFH/NCI phantom in sitting and standing postures was used the radiation transport code MCNPX. Whole body irradiations were performed using the recommended irradiation geometries by ICRP publication 116 antero-posterior (AP), postero-anterior (PA), right and left lateral, rotational (ROT) and isotropic (ISO). In most organs, the conversion coefficients DT/Phi were similar for both postures. However, relative differences were significant for organs located in the lower abdominal region, such as prostate, testes and urinary bladder, especially in the AP geometry. Results of effective dose conversion coefficients were 18% higher in the standing posture of the UFH/NCI phantom, especially below 100 MeV in AP and PA. In lateral geometry, the conversion coefficients values below 20 MeV were 16% higher in the sitting posture. In ROT geometry, the differences were below 10%, for almost all energies. In ISO geometry, the differences in E/Phi were negligible. The results of E/Phi of UFH/NCI phantom were in general below the results of the conversion coefficients provided in ICRP publication 116. PMID- 27664430 TI - A METHOD TO IMPROVE DOSE ASSESSMENT BY RECONSTRUCTION OF THE COMPLETE ISOTOPES INVENTORY. AB - Radiation shielding assessments may underestimate the expected dose if some isotopes at trace level are not considered in the isotopes inventory of the shielded radioactive materials. Indeed, information about traces is not often available. Nevertheless, the activation of some minor isotopic traces may significantly contribute to the dose build-up. This paper presents a new method (Isotopes Inventory Reconstruction-IIR) estimating the concentration of the minor isotopes in the irradiated material at the beginning of the cooling period. The method requires the solution of the inverse problem describing the irradiated material's decay. In a mixture of an irradiated uranium-plutonium oxide shielded by a set-up made of stainless-steel, porous polyethylene plaster and lead methyl methacrylate, the comparison between different methods proves that the IIR-method allows better assessment of the dose than other approximate methods. PMID- 27664431 TI - The Mayak Worker Dosimetry System (MWDS-2013): Internal Dosimetry Results. AB - The distribution of calculated internal doses has been determined for 8043 Mayak Production Associate (Mayak PA) workers. This is a subset of the entire cohort of 25 757 workers, for whom monitoring data are available. Statistical characteristics of point estimates of accumulated doses to 17 different tissues and organs and the uncertainty ranges were calculated. Under the MWDS-2013 dosimetry system, the mean accumulated lung dose was 185 +/- 594 mGy (geometric mean = 28 mGy; geometric standard deviation = 9.32; median value = 31 mGy; maximum value = 8980 mGy). The ranges of relative standard uncertainty were from 40 to 2200% for accumulated lung dose, from 25-90% to 2600-3000% for accumulated dose to different regions of respiratory tract, from 13-22% to 2300-2500% for systemic organs and tissues. The Mayak PA workers accumulated internal plutonium lung dose is shown to be close to log normal. The accumulated internal plutonium dose to systemic organs was close to a log triangle. The dependency of uncertainty of accumulated absorbed lung and liver doses on the dose estimates itself is also shown. The accumulated absorbed doses to lung, alveolar interstitial region, liver, bone surface cells and red bone marrow calculated both with MWDS-2013 and MWDS-2008 have been compared. In general, the accumulated lung doses increased by a factor of 1.8 in median value, while the accumulated doses to systemic organs decreased by factor of 1.3-1.4 in median value. For the cases with identical initial data, accumulated lung doses increased by a factor of 2.1 in median value, while accumulated doses to systemic organs decreased by 8 13% in median value. For the cases with both identical initial data and all of plutonium activity in urine measurements above the decision threshold, accumulated lung doses increased by a factor of 2.7 in median value, while accumulated doses to systemic organs increased by 6-12% in median value. PMID- 27664432 TI - OPTIMISATION OF PATIENT DOSE AND IMAGE QUALITY IN ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY: A PHANTOM-BASED EVALUATION. AB - A phantom-based study is presented aiming to optimise patient dose and image quality (IQ) in endoscopic retrograde cholangiopancreatography procedures, utilising a fluoroscopy system equipped with a flat panel detector. The patient thickness was simulated with various polymethyl methacrylate slabs, whilst IQ was evaluated using the Leeds test object. The main factors evaluated were phantom thickness, distance between phantom and detector, field of view and pulse rate. For all these factors, the dosemetric indices, entrance surface air kerma (ESAK) rate and ESAK per pulse, as well as the IQ parameters, signal-to-noise ratio and high contrast spatial resolution, were measured. Based on these measurements, the figure of merit (FOM) was estimated. The FOM and ESAK rate values indicated the optimum combination of the factors evaluated which could provide adequate clinical information, assuring minimum patient dose. PMID- 27664433 TI - Preparation of New Scintillation Imaging Material Composed of Scintillator-Silica Fine Powders and its Imaging of Tritium. AB - A new scintillation imaging material [scintillator-silica fine powder (FP)] was prepared using silica FPs and scintillator-encapsulating silica nanoparticles (NPs) (scintillator-silica NPs). The wt% values of scintillator-silica NPs on the scintillator-silica FPs were 38, 43, 36 and 44%. Scintillation images of 3H, 63Ni, 35S, 33P, 204Tl, 89Sr and 32P dropped on the scintillator-silica FPs were obtained at about 37 kBq per 0.1-10 ul with a charge-coupled device (CCD) imager for a 5 min exposure. In particular, high-intensity CCD images of 35S were selectively obtained using the 2.25, 4.77 and 10 um silica FPs with scintillator silica NPs owing to the residual S of dimethyl sulfoxide in the preparation. Scintillation images of 3H at 1670 +/- 9 Bq/0.5 ul and 347 +/- 6 Bq/0.5 ul dropped in a 2 mm hole on the scintillator-silica FPs (6.78 and 10 um) were also obtained using the CCD imager for a 2 h exposure. PMID- 27664434 TI - RADIOLOGICAL SAFETY ASSESSMENT FOR THE EXPERIMENTAL AREA OF A HYPER-INTENSE LASER WITH PEAK-POWER OF 1PW-CETAL. AB - Ultra-high intensity lasers in use are connected with ionizing radiation sources that raise a real concern in relation to installations, personnel, population and environment protection. The shielding of target areas in these facilities has to be evaluated from the conceptual stage of the building design. The sizing of the protective concrete walls was determined using computer codes such as Fluka. For the experiments to be carried out in the facility of the Center for Advanced Laser Technologies (CETAL), both proton beams with the energy of 100 MeV and electron beams with 300 MeV energy were considered to calculate the dimensions of structural shielding and to establish technical solutions fulfilling the radiation protection constraints imposed by the National Commission for Nuclear Activities Control. PMID- 27664435 TI - RADON MIGRATION IN SOIL AND ITS RELATION TO TERRESTRIAL GAMMA RADIATION IN DIFFERENT LOCATIONS OF THE GREEK EARLY WARNING SYSTEM NETWORK. AB - Radon concentration as function of the soil depth was measured during the years (2011-2015), in a location of the Aristotle University campus. Radium distribution in soil was found constant. On the contrary, as expected, radon concentration increases with soil depth. The experimental distribution was reproduced by solving the general transport equation (diffusion and advection). From the general radon migration (diffusion and advection) equation it was indirectly deduced, from the measured radon profile in the soil, the radon exhalation rate from the soil (26.7 +/- 4.5 Bq m-2 h-1). In the same location, during 2010-2015, 113 direct radon exhalation measurements were performed and give an average value for the 6 years of 21.1 +/- 3 Bq m-2 h-1. The comparison between the radon exhalation rates deduced by the indirect and direct method indicates the validity of the diffusion advection model predictions concerning the radon exhalation rate from soil. The relation between radon migration in soil and terrestrial gamma radiation was studied. In particular, in the present study was investigated the correlation between gamma radiation 1 m above soil and radon exhalation in six locations of the Greek early warning system network. A positive correlation between gamma dose rate in air and radon exhalation rate from soil was found. PMID- 27664436 TI - Efficient secretory expression of recombinant proteins in Escherichia coli with a novel actinomycete signal peptide. AB - In well-established heterologous hosts, such as Escherichia coli, recombinant proteins are usually intracellular and frequently found as inclusion bodies especially proteins possessing high rare codon content. In this study, successful secretory expression of three hydrolases, in a constructed inducible or constitutive system, was achieved by fusion with a novel signal peptide (Kp-SP) from an actinomycete. The signal peptide efficiently enabled extracellular protein secretion and also contributed to the active expression of the intracellular recombinant proteins. The thermophilic alpha-amylase gene of Bacillus licheniformis was fused with Kp-SP. Both recombinants, carrying inducible and constitutive plasmids, showed remarkable increases in extracellular and intracellular amylolytic activity. Amylase activity was observed to be > 10 fold in recombinant cultures with the constitutive plasmid, pBSPPc, compared to that in recombinants lacking Kp-SP. Further, the signal peptide enabled efficient secretion of a thermophilic cellulase into the culture medium, as demonstrated by larger halo zones and increased enzymatic activities detected in both constructs from different plasmids. For heterologous proteins with a high proportion of rare codons, it is difficult to obtain high expression in E. coli owing to the codon bias. Here, the fusion of an archaeal homologue of the amylase encoding gene, FSA, with Kp-SP resulted in > 5-fold higher extracellular activity. The successful extracellular expression of the amylase indicated that the signal peptide also contributed significantly to its active expression and signified the potential value of this novel and versatile signal peptide in recombinant protein production. PMID- 27664437 TI - Recombinant production, purification and characterization of vessel dilator in E. coli. AB - Vessel dilator is a 3.9-KDa potent anticancer peptide and a valuable candidate in the treatment of conditions such as congestive heart failure and acute renal failure amongst others. Here we report the recombinant production of vessel dilator in Escherichia coli. Three different synthetic ORF's dubbed VDI, VDII and VDIII, each encoding a trimmer of the vessel dilator peptide attached to a His tag sequence at their C- terminal, were synthesized and placed in pET21c expression vectors. The highest yield, following expression in E. coli BL21 (DE3), was recorded with VDII that carried the shortest fusion partner. Subsequent to the initial capture of the fusion protein by a Ni affinity column, the vessel dilator monomers were cleaved by trypsin treatment, and further purified to at least 90% homogeneity by anion exchange chromatography. De-novo sequencing and in vivo anticancer activity tests were used to verify the peptide sequence and its biological activity, respectively. The final yield was estimated to be approximately 15 mg of the purified vessel dilator per gram wet weight of the bacterial cells. PMID- 27664438 TI - Computationally Designed Armadillo Repeat Proteins for Modular Peptide Recognition. AB - Armadillo repeat proteins (ArmRPs) recognize their target peptide in extended conformation and bind, in a first approximation, two residues per repeat. Thus, they may form the basis for building a modular system, in which each repeat is complementary to a piece of the target peptide. Accordingly, preselected repeats could be assembled into specific binding proteins on demand and thereby avoid the traditional generation of every new binding molecule by an independent selection from a library. Stacked armadillo repeats, each consisting of 42 aa arranged in three alpha-helices, build an elongated superhelical structure. Here, we analyzed the curvature variations in natural ArmRPs and identified a repeat pair from yeast importin-alpha as having the optimal curvature geometry that is complementary to a peptide over its whole length. We employed a symmetric in silico design to obtain a uniform sequence for a stackable repeat while maintaining the desired curvature geometry. Computationally designed ArmRPs (dArmRPs) had to be stabilized by mutations to remove regions of higher flexibility, which were identified by molecular dynamics simulations in explicit solvent. Using an N-capping repeat from the consensus-design approach, two different crystal structures of dArmRP were determined. Although the experimental structures of dArmRP deviated from the designed curvature, the insertion of the most conserved binding pockets of natural ArmRPs onto the surface of dArmRPs resulted in binders against the expected peptide with low nanomolar affinities, similar to the binders from the consensus-design series. PMID- 27664439 TI - Making Sense of the Yeast Sphingolipid Pathway. AB - Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. PMID- 27664440 TI - Harsh environments and the evolution of multi-player cooperation. AB - The game-theoretic model in this paper provides micro-foundations for the effect a harsher environment on the probability of cooperation among multiple players. The harshness of the environment is alternatively measured by the degree of complementarity between the players' cooperative efforts in producing a public good, and by the number of attacks on an existing public good that the players can collectively defend, where it is shown that these two measures of the degree of adversity facing the players operate in a similar fashion. We show that the effect of the degree of adversity on the probability of cooperation is monotonous, and has an opposite sign for smaller and for larger cooperation costs. For intermediate cooperation costs, we show that the effect of a harsher environment on the probability of cooperation is hill-shaped. PMID- 27664442 TI - Freeze dried extracts of Bidens biternata (Lour.) Merr. and Sheriff. show significant antidiarrheal activity in in-vivo models of diarrhea. AB - ETHNOPHARMACOLOGICAL RELEVANCE OF THE STUDY: Diarrhea remains one of the main killers of children aged below five years. Traditional antidiarrheal remedies form a potentially viable source of novel low cost efficacious treatments in low resource settings. There is therefore a pressing need to scientifically evaluate these remedies. AIM OF THE STUDY: This study aimed to investigate the in vivo and in vitro antidiarrheal activity of freeze dried Bidens biternata, a herb used in traditional Ayurvedic medicine in the management of diarrhea. MATERIALS AND METHODS: In the castor oil test, twenty (20) adult Sprague-Dawley rats were randomized to a negative control (normal saline, n=5), a positive control (5mg/kg loperamide, n=5), and two test groups. The low dose test group received 200mg/kg Bidens biternata extract (n=5) while the high dose test group received 400mg/kg B. biternata extract (n=5). Castor oil (4ml/kg) was then administered to the animals one hour after administration of the respective treatments after which the total mass of fecal output excreted after four (4) hours was determined. In the charcoal meal test fifteen (15) Sprague Dawley rats were randomized to a control group (normal saline 5ml/kg orally, n=5), a positive control group (atropine sulfate 0.1mg/kg i.p., n=5) and a test group (400mg/kg B. biternata extract, n=5). Charcoal meal was then administered via oral gavage to each rat thirty (30) minutes after the administration of the various treatments. The distance covered by the charcoal meal from the pylorus was then determined after sacrifice of the animals thirty minutes after the meal. In the enteropooling test twenty (20) Sprague-Dawley rats were randomized to a control group (5% v/v ethanol in normal saline, n=5), a positive control group (5mg/kg loperamide, n=5) and a test group (400mg/kg B. biternata extract, n=5). For each group prostaglandin E2 (PGE2) (100MUg/kg) was administered immediately after the treatments. The animals were then sacrificed half an hour later and the volume of the small intestine contents determined. The effects of different concentrations of B. biternata extract (0.5. 1.0, 2.0, 3.0 and 5.0mg/ml) on jejunal contraction were investigated and a dose-response curve constructed using the experimental data after which The ED50 dose was determined. The effect of tamsulosin (alpha1 adrenergic blocker), yohimbine (alpha2 adrenergic blocker), propranolol (beta adrenergic blocker) and naloxone (MU opioid blocker) on the contractile activity of the extract were also investigated. The experimental data were expressed as mean+/-standard error of mean (SEM) and then analyzed using one-way ANOVA followed by Tukey's post hoc test in cases of significance (set at p<0.05). RESULTS: The freeze dried extracts of B. biternata had significant antidiarrheal effects in the castor oil induced diarrhea model (p<0.01) with the highest activity being observed at the 400mg/kg dosage level (1.66+/-0.81g vs. 4.54+/ 0.51g control, p=0.01). B. biternata extract had significant effects on intestinal motility in the charcoal meal test compared to the control group (43.61+/-4.42% vs. 60.54+/-3.33%: p<0.05). B. biternata extract had a significant effect on PGE2 induced enteropooling (3.06+/-0.07ml vs. 4.74+/-0.10ml; p<0.001). The freeze dried extracts of B. biternata had a significant negative effect on the contractility of the isolated rabbit jejunum (p<0.001). The effects of the extract were significantly attenuated by tamsulosin (53.94+/-4.20% vs. 80.57+/ 4.09%; p<0.01) and naloxone (53.94+/-4.20% vs. 73.89+/-7.26%; p<0.05). Yohimbine (p>0.05) and propranolol (p>0.05) however did not have any significant effect on the contractile activity of the extract. CONCLUSIONS: The freeze dried extract of B. biternata possess significant antidiarrheal activity in both in vitro and in vivo models which appears to be mediated by modulating both the intestinal motility as well as the secretory activity. The results of this study also validate its traditional use as an antidiarrheal remedy. PMID- 27664443 TI - The DD Check App for prevention and control of digital dermatitis in dairy herds. AB - Digital dermatitis (DD) is the most important infectious claw disease in the cattle industry causing outbreaks of lameness. The clinical course of disease can be classified using 5 clinical stages. M-stages represent not only different disease severities but also unique clinical characteristics and outcomes. Monitoring the proportions of cows per M-stage is needed to better understand and address DD and factors influencing risks of DD in a herd. Changes in the proportion of cows per M-stage over time or between groups may be attributed to differences in management, environment, or treatment and can have impact on the future claw health of the herd. Yet trends in claw health regarding DD are not intuitively noticed without statistical analysis of detailed records. Our specific aim was to develop a mobile application (app) for persons with less statistical training, experience or supporting programs that would standardize M stage records, automate data analysis including trends of M-stages over time, the calculation of predictions and assignments of Cow Types (i.e., Cow Types I-III are assigned to cows without active lesions, single and repeated cases of active DD lesions, respectively). The predictions were the stationary distributions of transitions between DD states (i.e., M-stages or signs of chronicity) in a class structured multi-state Markov chain population model commonly used to model endemic diseases. We hypothesized that the app can be used at different levels of record detail to discover significant trends in the prevalence of M-stages that help to make informed decisions to prevent and control DD on-farm. Four data sets were used to test the flexibility and value of the DD Check App. The app allows easy recording of M-stages in different environments and is flexible in terms of the users' goals and the level of detail used. Results show that this tool discovers trends in M-stage proportions, predicts potential outbreaks of DD, and makes comparisons among Cow Types, signs of chronicity, scorers or pens. The DD Check App also provides a list of cows that should be treated augmented by individual Cow Types to help guide treatment and determine prognoses. Producers can be proactive instead of reactive in controlling DD in a herd by using this app. The DD Check App serves as an example of how technology makes knowledge and advice of veterinary epidemiology widely available to monitor, control and prevent this complex disease. PMID- 27664441 TI - Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN. However, the underlying mechanisms of MC-TG for treating DN are still unknown. AIM OF THE STUDY: To explore the role of ER stress-related inflammatory responses in the progression of DN, and to investigate the underlying protective mechanisms of MC-TG in kidney damage. MATERIALS AND METHODS: DN rats and advanced glycation end-products (AGEs) induced HBZY-1 cell dysfunction were established to evaluate the protective effect of MC-TG on ameliorating renal injury. Evaluation of pathological lesions was performed by Masson staining and transmission electron microscopy (TEM). Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), glucose regulated protein 78 (GRP78/Bip), as well as spliced X box binding protein 1(XBP-1(s)) levels in rat serum were detected by an enzyme-linked immunosorbent assay (ELISA). Furthermore, western blotting (WB) was applied to detect the protein expressions including IL 6, MCP-1, intercellular cell adhesion molecule-1 (ICAM-1), GRP78/Bip, XBP-1 (s), phosphorylated inositol-requiring enzyme-1alpha (p-IRE1alpha), cleaved activating transcription factor 6 (ATF6), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), and phosphorylated nuclear factor kappaB p65 (p-NF-kappaB p65) in vivo and in vitro. Immunohistochemistry (IHC) was carried out to determine the phosphorylation of IRE1alpha and NF-kappaB p65 in kidney tissues. RESULTS: Pretreatment with MC-TG could markedly improve renal insufficiency and pathologic changes. It could down-regulate ER stress-related factors GRP78/Bip, XBP-1(s) levels, and also reduce the pro-inflammatory molecules IL-6, MCP-1, and ICAM-1 expressions. Furthermore, a significant decrease in phosphorylation of IRE1alpha and NF-kappaB p65 by the treatment of MC-TG. CONCLUSIONS: These findings indicated that MC-TG ameliorated ER stress-related inflammation in the pathogenesis of DN, wherein the protective mechanism might be associated with the inhibition of IRE1/NF-kappaB activation. Thus, MC-TG might be a potential therapeutic candidate for the prevention and treatment of DN. PMID- 27664444 TI - "Who's been a good dog?" - Owner perceptions and motivations for treat giving. AB - Complex relationships commonly exist between owners and their companion animals, particularly around feeding behaviour with an owner's affection or love for their animal most pronounced through the provision of food. It is notable that the pet food market is experiencing strong year-on-year growth in sales of dog and cat treats. Recognising the impact of treat giving in pet nutrition, the objective of the study was to investigate owner attitudes and motivations towards feeding treats (shop bought and other) to their dogs. A researcher-mediated questionnaire consisting of both quantitative and qualitative questions was used to interview dog owners (n=280) at two locations: an out-of-town retail park and a country park in the East Midlands. Owners almost unanimously viewed the word 'treat' within a nutritional context, as opposed to a new toy or other pleasure. The majority (96%) of owners interviewed reported feeding treats to their dog, with 69% feeding shop-bought treats on a daily basis. A wide range of treats was reportedly given by owners and the majority of owners interviewed fed multiple treat types. No association was found between owner age and frequency of shop bought treats fed (P=0.659) nor between owner age and frequency of food given to the dog from the owner's plate (P=0.083). A wide range of foods which would not be considered balanced for the animal's nutritional requirements was viewed as a treat by some dog owners. A range of positive and negative views around the feeding of treats were expressed by dog owners, with some citing beneficial effects while others were clearly aware of the association between treat feeding and potential weight gain/obesity. Owner views included themes around positive reinforcement and responsibility but also reflected relational aspects of the human-animal bond. The results of the study show that treat giving is commonplace in feeding regimes and that treats are embedded in the feeding behaviour of many dog owners. However, the different views expressed around the motivations for, and feeding of, dog treats, reinforce the need to better understand owner psychology linked to this area, and the role this may play in the growing pet obesity epidemic. PMID- 27664445 TI - Broken biosecurity? Veterinarians' framing of biosecurity on dairy farms in England. AB - There is seen to be a need for better biosecurity - the control of disease spread on and off farm - in the dairy sector. Veterinarians play a key role in communicating and implementing biosecurity measures on farm, and little research has been carried out on how veterinarians see their own and farmers' roles in improving biosecurity. In order to help address this gap, qualitative interviews were carried out with 28 veterinarians from Royal College of Veterinary Surgeon farm accredited practices in England. The results were analysed using a social ecology framework and frame analysis to explore not only what barriers vets identified, but also how vets saw the problem of inadequate biosecurity as being located. Veterinarians' frames of biosecurity were analysed at the individual, interpersonal and contextual scales, following the social ecology framework, which see the problem in different ways with different solutions. Farmers and veterinarians were both framed by veterinarians as individualised groups lacking consistency. This means that best practice is not spread and veterinarians are finding it difficult to work as a group to move towards a "predict and prevent" model of veterinary intervention. But diversity and individualism were also framed as positive and necessary among veterinarians to the extent that they can tailor advice to individual farmers. Veterinarians saw their role in educating the farmer as not only being about giving advice to farmers, but trying to convince the farmer of their perspective and values on disease problems. Vets felt they were meeting with limited success because vets and farmers may be emphasising different framings of biosecurity. Vets emphasise the individual and interpersonal frames that disease problems are a problem on farm that can and should be controlled by individual farmers working with vets. According to vets, farmers may emphasise the contextual frame that biosecurity is largely outside of their control on dairy farms because of logistical, economic and geographical factors, and so some level of disease on dairy farms is not entirely unexpected or controllable. There needs to be a step back within the vet-farmer relationship to realise that there may be different perspectives at play, and within the wider debate to explore the question of what a biosecure dairy sector would look like within a rapidly changing agricultural landscape. PMID- 27664446 TI - Mycobacterium avium ssp. paratuberculosis detection in animals, food, water and other sources or vehicles of human exposure: A scoping review of the existing evidence. AB - Mycobacterium avium ssp. paratuberculosis is the etiologic agent of Johne's disease in ruminants and is hypothesized to be an infectious cause of Crohn's disease, as well as some other human diseases. Due to key knowledge gaps, the potential public health impact of M. paratuberculosis is unknown. This scoping review aims to identify and characterised the evidence on potential sources and vehicles of M. paratuberculosis exposure for humans to better understand how exposure is likely to occur. Evidence from 255 primary research papers is summarized; most examined the prevalence or concentration of M. paratuberculosis in animals (farmed domestic, pets and wildlife) (n=148), food for human consumption (62) (milk, dairy, meat, infant formula) or water (drinking and recreational) and the environment (farm, pasture and areas affected by runoff water) (20). The majority of this research has been published since 2000 (Figure- abstract). Nine case-control studies examining risk factors for Crohn's disease highlighted significant associations with the consumption of processed meats and cheese, while direct contact with ruminants, high risk occupations (farmer, veterinarian), milk consumption and water source were factors not associated with the disease and/or M. paratuberculosis exposure status. Molecular epidemiology studies demonstrated strain-sharing between species. Produce and seafood were the only previously suggested sources of human exposure for which there was no supporting evidence identified in this scoping review. The results of this review indicate that ruminant populations from around the globe are infected with M. paratuberculosis and many non-ruminant species have also been found to carry or be infected with M. paratuberculosis. Several potential sources for human exposure to M. paratuberculosis were identified; however there remain important gaps in quantitative information on the prevalence and concentration of M. paratuberculosis in contaminated sources of exposure. This information is critical to understanding the risk of exposure, opportunities for risk mitigation interventions and modelling exposures to distill the importance of various sources of human exposure to M. paratuberculosis including direct contact with animals and the environment as well as consumption of contaminated foods and water. Results of this study may be used to prioritize future research and to support evidence-informed decision-making on the M. paratuberculosis issue. PMID- 27664447 TI - A retrospective epidemiological analysis of risk factors for a primary necropsy diagnosis of bovine respiratory disease. AB - Bovine respiratory disease (BRD) is a multifactorial disease and the primary cause of both bovine morbidity and mortality in Ireland. The risk factors associated with a primary necropsy diagnosis of BRD among cattle in the traditional (non-feedlot) husbandry systems prevalent in Ireland have not been investigated previously. The aim of this case-control study was to investigate those risk factors among cattle of all ages over an 8 year period. A total of 3,090 BRD cases and 5,236 controls were matched by submitting veterinary practitioner. Univariable and multivariable analyses were performed to examine the association of selected animallevel, herd-level and environmental risk factors with case or control status using a conditional logistical regression model. Male cattle aged more than 31 days were significantly more likely to record a primary necropsy diagnosis of BRD than female cattle. Older cattle of both sexes were at increased odds of a BRD necropsy diagnosis than younger calves with the exception of female cattle aged greater than 165 days. The risk of a primary necropsy diagnosis of BRD increased with increasing herd size and decreased with increasing time in days since the last animal movement into the submitting herd. There were significantly reduced odds of a primary necropsy diagnosis of BRD in the summer (June to August) when compared with the autumn (September to November). These findings identify significant risk factors for a necropsy diagnosis of BRD under non-feedlot-type husbandry conditions. PMID- 27664448 TI - Enhanced surveillance of shellfish mortality to improve early detection and investigation of outbreaks of exotic or emerging infectious diseases: An example of a mass mortality outbreak of mussels, France 2014. AB - This paper explores the relevance and feasibility of enhanced surveillance of mussel-related mortality based on regular telephone interviews of a key informant in a farming community. Based on qualitative analyses of data collected through semi-structured interviews, this method of participatory disease surveillance enabled the retrieval of high quality data during an outbreak of mussel mortality which occurred in Pertuis Charentais, France, in 2014. The findings illustrated that such an enhanced surveillance approach compared with the institutional shellfish health surveillance system could improve the early detection of outbreaks of mussel mortality by one week. This approach enabled a detailed description of the outbreak, showing higher incidence proportion in the Northern water bodies. It also captured relevant data for hypothesis generation for further outbreak investigations, integrating a global view of the health and disturbance of the coastal marine ecosystem. However, to be effective and sustainable, this flexible approach requires a pre-existing knowledge of the structure of the information network of the farmers' community. Such a community based enhanced surveillance could increase the reactivity of the entire system to enable the earliest possible and most appropriate interventions to protect shellfish populations against exotic or emerging infectious diseases. This would also help to improve the vigilance of mussel farmers and foster their commitment, which is an essential element for sustainable shellfish health surveillance. PMID- 27664449 TI - Cost-benefit analysis of foot and mouth disease control in Ethiopia. AB - Foot and mouth disease (FMD) occurs endemically in Ethiopia. Quantitative insights on its national economic impact and on the costs and benefits of control options are, however, lacking to support decision making in its control. The objectives of this study were, therefore, to estimate the annual costs of FMD in cattle production systems of Ethiopia, and to conduct an ex ante cost-benefit analysis of potential control alternatives. The annual costs of FMD were assessed based on production losses, export losses and control costs. The total annual costs of FMD under the current status quo of no official control program were estimated at 1354 (90% CR: 864-2042) million birr. The major cost (94%) was due to production losses. The costs and benefits of three potential control strategies: 1) ring vaccination (reactive vaccination around outbreak area supported by animal movement restrictions, 2) targeted vaccination (annual preventive vaccination in high risk areas plus ring vaccination in the rest of the country), and 3) preventive mass vaccination (annual preventive vaccination of the whole national cattle population) were compared with the baseline scenario of no official control program. Experts were elicited to estimate the influence of each of the control strategies on outbreak incidence and number of cases per outbreak. Based on these estimates, the incidence of the disease was simulated stochastically for 10 years. Preventive mass vaccination was epidemiologically the most efficient control strategy by reducing the national outbreak incidence below 5% with a median time interval of 3 years, followed by targeted vaccination strategy with a corresponding median time interval of 5 years. On average, all evaluated control strategies resulted in positive net present values. The ranges in the net present values were, however, very wide, including negative values. The targeted vaccination strategy was the most economic strategy with a median benefit cost ratio of 4.29 (90%CR: 0.29-9.63). It was also the least risky strategy with 11% chance of a benefit cost ratio of less than one. The study indicates that FMD has a high economic impact in Ethiopia. Its control is predicted to be economically profitable even without a full consideration of gains from export. The targeted vaccination strategy is shown to provide the largest economic return with a relatively low risk of loss. More studies to generate data, especially on production impact of the disease and effectiveness of control measures are needed to improve the rigor of future analysis. PMID- 27664450 TI - Correlations between peripheral parasite load and common clinical and laboratory alterations in dogs with visceral leishmaniasis. AB - Intensity of peripheral parasite infection has an important role in the transmission of Leishmania spp. from one host to another. As parasite load quantification is still an expensive procedure to be used routinely in epidemiological surveillance, the use of surrogate predictors may be an important asset in the identification of dogs with high transmitting ability. The present study examined whether common clinical and laboratory alterations can serve as predictors of peripheral parasitism in dogs naturally infected with Leishmania spp. Thirty-seven dogs were examined in order to establish correlations between parasite load (PL) in multiple peripheral tissues and common clinical and laboratory findings in canine visceral leishmaniasis (CVL). Quantitative polymerase chain reaction was employed to determine PL in conjunctival swabs, ear skin, peripheral blood and buffy coat. Additionally, a series of hematological, biochemical and oxidative stress markers were quantified. Correlations between net peripheral infection and severity of clinical alterations and variation in laboratory parameters were assessed through a new analytical approach, namely Compressed Parasite Load Data (CPLD), which uses dimension reduction techniques from multivariate statistics to summarize PL across tissues into a single variable. The analysis revealed that elevation in PL is positively correlated with severity of clinical sings commonly observed in CVL, such as skin lesions, ophthalmic alterations, onycogriphosis, popliteal lymphadenomegaly and low body mass. Furthermore, increase in PL was found to be followed by intensification of non-regenerative anemia, neutrophilia, eosinopenia, hepatic injury and oxidative imbalance. These results suggest that routinely used clinical and laboratory exams can be predictive of intensity of peripheral parasite infection, which has an important implication in the identification of dogs with high transmitting ability. PMID- 27664451 TI - Risk assessment and management of brucellosis in the southern greater Yellowstone area (I): A citizen-science based risk model for bovine brucellosis transmission from elk to cattle. AB - Livestock producers and state wildlife agencies have used multiple management strategies to control bovine brucellosis in the Greater Yellowstone Area (GYA). However, spillover from elk to domestic bison and cattle herds continues to occur. Although knowledge is increasing about the location and behavior of elk in the SGYA, predicting spatiotemporal overlap between elk and cattle requires locations of livestock operations and observations of elk contact by producers. We queried all producers in a three-county area using a questionnaire designed to determine location of cattle and whether producers saw elk comingle with their animals. This information was used to parameterize a spatially-explicit risk model to estimate the number of elk expected to overlap with cattle during the brucellosis transmission risk period. Elk-cattle overlap was predicted in areas further from roads and forest boundaries in areas with wolf activity, with higher slopes, lower hunter densities, and where the cost-distance to feedgrounds was very low or very high. The model was used to estimate the expected number of years until a cattle reactor will be detected, under alternative management strategies. The model predicted cattle cases every 4.28 years in the highest risk herd unit, a higher prediction than the one case in 26 years we have observed. This difference likely indicates that ongoing management strategies are at least somewhat effective in preventing potential elk-cattle brucellosis transmission in these areas. Using this model, we can infer the expected effectiveness of various management strategies for reducing the risk of brucellosis spillover from elk to cattle. PMID- 27664452 TI - Ostertagia spp., rumen fluke and liver fluke single- and poly-infections in cattle: An abattoir study of prevalence and production impacts in England and Wales. AB - This study aims at investigating the occurrence, risk factors and production impacts on beef carcass parameters of three of the most important cattle helminth infections in England and Wales. Abomasa, reticulorumens and livers from healthy cattle were collected and examined post-mortem quarterly over a one year period in an abattoir in South-West England. Specific viscera from 974 cattle were collected, examined and scored for Ostertagia spp., adult rumen fluke and liver fluke lesions/presence. A total of 89%, 25% and 29% of the carcasses had lesions/presence of Ostertagia spp., rumen fluke and liver fluke, respectively, and 39% had presence of helminth co-infection. Animal demographic and carcass parameters associated with helminth infections were investigated using multilevel multinomial and multilevel linear mixed models respectively. After adjusting for other factors, significant differences in the distribution of helminth infections were observed among cattle by type of breed, animal category (cow, heifer, steer and young bull), age, season and concurrent helminth infections. Compared to carcasses free of helminths, carcasses presenting solely Ostertagia Spp. lesions or adult rumen fluke had significantly lower cold carcass weight (coef.: -30.58 [ 50.92;-10.24] and -50.34 [-88.50;-12.18]) and fat coverage (coef.: -3.28 [-5.56; 1.00] and -5.49 [-10.28;-0.69]) and carcasses presenting solely liver fluke lesions had significantly lower conformation grade (coef.: -3.65 [-6.98;-0.32]). Presence of helminth poly-infections was negatively associated with cold carcass weight. PMID- 27664453 TI - Risk factors associated with contagious caprine pleuro-pneumonia in goats in pastoral areas in the Rift Valley region of Kenya. AB - A cross-sectional study to determine risk factors associated with sero-prevalence of contagious caprine pleuro-pneumonia (CCPP) in goats was carried out between the months of March, 2014 and March, 2015 in Pokot East, Turkana West and Kajiado Central Sub-counties. A semi-structured questionnaire focusing on risk factors for CCPP was completed for each flock whose serum samples were collected. A logistic regression model was developed to assess the association between the risk factors and CCPP sero-positivity. Of the 54 flocks, 49 (90.7%) presented at least one sero-positive animal. Two hundred and four of the 432 goats tested sero positive at monoclonal antibody based competitive Enzyme-linked immuno-sorbent assay (c-ELISA), hence a sero-prevalence of 47.2% (95% CI=42.5- 51.9). Previous exposure of flocks to CCPP (p<0.001, OR=52.8; CI=6.45, 432), distant sources of veterinary drugs (p<0.001, OR=6.17; CI=3.41, 11.1), movement of goats to dry season feeding areas (p<0.001, OR=4.31; CI=2.39, 7.75) and markets as a source of new introductions to the flock (p=0.033, OR=1.86; CI=1.05, 3.27) were identified as risk factors significantly associated with CCPP sero-prevalence. The findings provide further evidence supporting the high prevalence and endemic state of the disease in pastoral flocks and hence there is need for adequate measures to be put in place to control the disease effectively. PMID- 27664454 TI - The epidemiological and economic effects from systematic depopulation of Norwegian marine salmon farms infected with pancreas disease virus. AB - Pancreas disease (PD) is a viral disease associated with significant economic losses in Scottish, Irish, and Norwegian marine salmon aquaculture. In this paper, we investigate how disease-triggered harvest strategies (systematic depopulation of infected marine salmon farms) towards PD can affect disease dynamics and salmon producer profits in an endemic area in the southwestern part of Norway. Four different types of disease-triggered harvest strategies were evaluated over a four-year period (2011-2014), each scenario with different disease-screening procedures, timing for initiating the harvest interventions on infected cohorts, and levels of farmer compliance to the strategy. Our approach applies a spatio-temporal stochastic model for simulating the spread of PD in the separate scenarios. Results from these simulations were then used in cost-benefit analyses to estimate the net benefits of different harvest strategies over time. We find that the most aggressive strategy, in which infected farms are harvested without delay, was most efficient in terms of reducing infection pressure in the area and providing economic benefits for the studied group of salmon producers. On the other hand, lower farm compliance leads to higher infection pressure and less economic benefits. Model results further highlight trade-offs in strategies between those that primarily benefit individual producers and those that have collective benefits, suggesting a need for institutional mechanisms that address these potential tensions. PMID- 27664455 TI - Custom fabrication of biomass containment devices using 3-D printing enables bacterial growth analyses with complex insoluble substrates. AB - Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interaction between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. We applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present. PMID- 27664456 TI - Going from Darkness to Gray Zones of Knowledge: The Role of Biomarkers on Major Adverse Cardiovascular Events after Carotid Interventions. PMID- 27664457 TI - Disgust evoked by strong wormwood bitterness influences the processing of visual food cues in women: An ERP study. AB - The perception of intense bitterness is associated with disgust and food rejection. The present cross-modal event-related potential (ERP) study investigated whether a bitter aftertaste is able to influence affective ratings and the neuronal processing of visual food cues. We presented 39 healthy normal weight women (mean age: 22.5 years) with images depicting high-caloric meat dishes, high-caloric sweets, and low-caloric vegetables after they had either rinsed their mouth with wormwood tea (bitter group; n = 20) or water (control group; n = 19) for 30s. The bitter aftertaste of wormwood enhanced fronto-central early potentials (N100, N200) and reduced P300 amplitudes for all food types (meat, sweets, vegetables). Moreover, meat and sweets elicited higher fronto central LPPs than vegetables in the water group. This differentiation was absent in the bitter group, which gave lower arousal ratings for the high-caloric food. We found that a minor intervention ('bitter rinse') was sufficient to induce changes in the neuronal processing of food images reflecting increased early attention (N100, N200) as well as reduced affective value (P300, LPP). Future studies should investigate whether this intervention is able to influence eating behavior. PMID- 27664458 TI - An examination of the startle response during upper limb stretch perturbations. AB - Unexpected presentation of a startling auditory stimulus (SAS>120 decibels) in a reaction time (RT) paradigm results in the startle reflex and an early release (<100ms) of the preplanned motor response (StartReact effect). Mechanical perturbations applied to the upper limbs elicit short- (M1) and long-latency (M2) stretch reflexes and have also been shown to initiate intended motor responses early (<100ms). Ravichandran et al. (2013) recently proposed that unexpected delivery of a perturbation could also elicit a startle response and therefore the StartReact effect may be responsible for the early trigger of a preplanned response. To investigate this further, we examined startle incidence, RT, and stretch reflex modulation for both expected and unexpected perturbations. In Experiment 1, participants performed active (ACT) and passive (DNI) conditions to an expected large perturbation (similar to previous studies examining M2). The startle response was not observed; however, the perturbation still elicited the voluntary response at short latency (<100ms) and goal-dependent modulation of the M2 response was observed. In Experiment 2, participants performed ACT and DNI conditions to a weak auditory stimulus or a small wrist perturbation. On unexpected trials we probed startle circuitry with a large perturbation or SAS. The SAS consistently elicited a startle response in both ACT and DNI conditions, but startle-like activity was only observed on 17.4% of ACT perturbation probe trials. Our findings suggest that while unexpected upper limb perturbations can be startling, startle triggering of the preplanned voluntary response is not the primary mechanism responsible for goal-dependent modulation of the M2 response. PMID- 27664459 TI - Immunohistochemical investigation of the internal structure of the mouse subiculum. AB - The subiculum is the output component of the hippocampal formation and holds a key position in the neural circuitry of memory. Previous studies have demonstrated the subiculum's connectivity to other brain areas in detail; however, little is known regarding its internal structure. We investigated the cytoarchitecture of the temporal and mid-septotemporal parts of the subiculum using immunohistochemistry. The border between the CA1 region and subiculum was determined by both cytoarchitecture and zinc transporter 3 (ZnT3) immunoreactivity (IR), whereas the border between the subiculum and presubiculum (PreS) was partially indicated by glutamate receptor 1 (GluR1)-IR. The subiculum was divided into proximal and distal subfields based on cytoarchitecture and immunohistochemistry for calbindin (CB), nitric oxide synthase (NOS) and Purkinje cell protein 4 (PCP4). The proximal subiculum (defined here as subiculum 2) was composed of five layers: the molecular layer (layer 1), the medium-sized pyramidal cell layer (layer 2) that contained NOS- and PCP4-positive neurons, the large pyramidal cell layer (layer 3) characterized by the accumulation of ZnT3- (more proximally) and vesicular glutamate transporter 2-positive (more distally) boutons, layer 4 containing polymorphic cells, and the deepest layer 5 composed of PCP4-positive cells with long apical dendrites that reached layer 1. The distal subiculum (subiculum 1) consisting of smaller neurons did not show these features. Quantitative analyses of the size and numerical density of somata substantiated this delineation. Both the proximal-distal division and five layered structure in the subiculum 2 were confirmed throughout the temporal two thirds of the subiculum. These findings will provide a new structural basis for hippocampal investigations. PMID- 27664460 TI - The impact of l-dopa on attentional impairments in a rat model of Parkinson's disease. AB - Attentional deficits including difficulty in switching attention between tasks or rules, sustaining attention, and selectively attending to specific stimuli are commonly seen in patients with Parkinson's disease (PD). While these deficits are frequently reported, it is unclear how traditional dopamine replacement therapy such as l-dopa affects these deficits. In a rat model of PD in which dopamine is unilaterally depleted with a 6-hydroxydopamine infusion to the medial forebrain bundle, we first examined the impact of acute and chronic l-dopa treatment on attention switching as modeled by disengagement behavior (i.e. the ability to disengage from an on-going behavior such as eating or drinking to attend to perioral stimulation). Then, in a separate experiment, we evaluated the effects of l-dopa treatment on selective and sustained attention deficits using a five choice task. Our data suggest that the l-dopa dose necessary to recover motor function can successfully restore attention switching behavior (i.e. disengagement behavior), but further worsens performance in the selective and sustained attention task. Furthermore, this same dose was responsible for inducing dyskinesias in rats given chronic daily injections. Taken together, these findings demonstrate that dopamine replacement therapy may not be sufficient for treating all types of attentional dysfunction occurring in PD. PMID- 27664461 TI - Alterations in membrane trafficking and pathophysiological implications in lysosomal storage disorders. AB - Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes. The progressive accumulation of uncleaved substrates occurs in multiple organs and finally causes a broad spectrum of different pathologies including visceral, neurological, skeletal and hematologic manifestations. Besides deficient lysosomal enzymes and transporters other defects may lead to lysosomal storage disorders, including activator defects, membrane defects or defects in modifier proteins. In this review we concentrate on four different lysosomal storage disorders: Niemann-Pick type C, Fabry disease, Gaucher disease and Pompe disease. While the last three are caused by defective lysosomal hydrolases, Niemann-Pick type C is caused by the inability to export LDL-derived cholesterol out of the lysosome. We want to emphasise potential implications of membrane trafficking defects on the pathology of these diseases, as many mutations interfere with correct lysosomal protein trafficking and alter cellular lipid homeostasis. Current therapeutic strategies are summarised, including substrate reduction therapy as well as pharmacological chaperone therapy which directly aim to improve folding and lysosomal transport of misfolded mutant proteins. PMID- 27664462 TI - Dieting to Disordered Restricting. PMID- 27664463 TI - Males With Restrictive Eating Disorders: Barriers to Their Care. PMID- 27664464 TI - Expanding Adolescent Depression Prevention Through Simple Communication Technologies. PMID- 27664465 TI - From Advocacy to Action in Global Adolescent Health. AB - In May 2016, The Lancet published a report titled, "Our Future: A Lancet Commission on Adolescent Health and Wellbeing," the culmination of three years of work from a geographically diverse interdisciplinary group. The report argued that healthy growth across adolescence and young adulthood shapes life course and intergenerational trajectories so that health investments yield a "triple dividend." With current global interest in adolescent health at an unprecedented level, it outlines three next steps to advance from advocacy to effective action: (1) there is a pressing need for comprehensive and integrated strategies, inclusive of, but extending beyond, sexual and reproductive health, and HIV; (2) interventions should address both adolescent health service coverage and determinants of health that lie in sectors such as education, justice, transport, and industry and employment, as well as families and local communities; and (3) scale-up of responses will require not only investments in country-level capacities for measuring need and responding with evidence-based practice but also the establishment of processes for accountability and meaningful youth engagement. PMID- 27664466 TI - International Youth Justice Systems: Promoting Youth Development and Alternative Approaches: A Position Paper of the Society for Adolescent Health and Medicine. AB - Youth incarceration is an international public health concern among developed and developing countries. Worldwide, youth are held in incarceration, detention, and other secure settings that are inappropriate for their age and developmental stages, jeopardizing their prosocial development, and reintegration into society. Youth incarceration lacks evidence and cost-effectiveness. The well-being of youth is a key indicator of the welfare of families, communities, and society at large; therefore, the Society for Adolescent Health and Medicine (SAHM) supports a paradigm shift in the role of the justice system as it relates to treatment of youth. SAHM recommends justice systems focus greater attention and resources on identifying and reducing the antecedents of high-risk and criminal behaviors, recognizing the rights and freedom of young persons, and prioritizing the well being of youth over punitive measures that may harm and disrupt healthy adolescent development. SAHM supports the following positions: (1) incarceration is a last option for selected offenders who have committed the most serious violent crimes and are unable to remain safely in the community; (2) youth justice policies, programs, and practices affecting youth be evidence based and trauma informed; (3) youth justice policies, programs, and practices must incorporate research and ongoing program evaluation; (4) youth justice policies shall protect the privacy and dignity of children younger than 18 years; and (5) health care professionals and media will promote positive portrayals of youth in healthy relationships within their communities and reduce representations and images of youth that are negative, violent, deviant, and threatening. PMID- 27664467 TI - Long-term survival and vitality outcomes of permanent teeth following deep caries treatment with step-wise and partial-caries-removal: A Systematic Review. AB - OBJECTIVES: A systematic review was performed to compare the long-term survival of deep dentine caries-affected permanent teeth treated with partial-caries removal (PCR) versus similar teeth treated with stepwise-caries-removal techniques (SWT). DATA: Clinical studies investigating long-term PCR and SWT outcomes in unrestored permanent teeth with deep dentine caries were evaluated. Failures were defined as loss of pulp vitality or restorative failures following treatment. SOURCES: PubMed, Web of Science, Dentistry and Oral Sciences Source, and Central databases were systematically searched. STUDY SELECTION: From 136 potentially relevant articles, 9 publications utilizing data from 5 studies (2 RCTs, and 3 observational case-series) reporting outcomes for 426 permanent teeth over two to ten years were analyzed. Regarding restorative failures, >88% success at two years for both techniques was reported. For loss of pulp vitality, observational studies reported >96% vitality at two years for each technique, while one RCT reported significantly higher vitality (p<0.05) at three years for PCR (96%) compared to SWT (83%). Risk of bias was high in all studies. CONCLUSION: Successful vitality and restorative outcomes for both PCR and SWT have been demonstrated at two years and beyond in permanent teeth with deep dentine caries. Partial-caries-removal may result in fewer pulpal complications over a three year period than SWT, although claims of a therapeutic advantage are based on very few, limited-quality studies. CLINICAL SIGNIFICANCE: Partial-caries removal and SWT are deep caries management techniques that reduce pulp exposure risk. Permanent teeth with deep dentine caries treated with either technique have a high likelihood for survival beyond two years. PMID- 27664468 TI - Novel non-invasive reinforcement of MOD cavities on endodontically treated teeth. AB - OBJECTIVES: To evaluate the biomechanical influence of reconnecting the buccal and lingual walls of endodontically treated lower molar with a large MOD cavity. METHODS: 3D models were created from a micro-CT scan of an extracted intact lower human molar. Finite element analysis was then used to compare the stress distribution and displacement of the structures between different models: Unrestored MOD on ETT (Unrest), MOD on ETT restored with composite resin (Norm), MOD on ETT reinforced with a non-invasive ring (Ring) and intact tooth as the control (Int). RESULTS: This study showed that the Unrest model presented the highest stress values at the cervical level. The non-invasive Ring model showed the lowest stress values at the cervical level, and the lowest deflection of the cusps. CONCLUSIONS: Mechanically reconnecting the remaining tooth structures has a direct positive effect on stress distribution and deformation of the remaining structures. CLINICAL RELEVANCE: Reinforcing ETT in a non-invasive direct approach is efficient in terms of preserving sound tooth structures, reducing the time of treatment and eliminating the laboratory steps required to create the restorations. PMID- 27664469 TI - PARPing for balance in the homeostasis of poly(ADP-ribosyl)ation. AB - Despite more than 50 years of research, the vast majority of the biology of poly(ADP-ribosyl)ation (PARylation) still remains a gross mystery. Originally described to be a part of the DNA repair machinery, poly(ADP-ribose) (PAR) is synthesized immediately by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) upon DNA damage and then rapidly removed by degrading enzymes. PAR provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. Thus, the multifaceted PARylation system, consisting of PAR itself and its synthesizers and erasers, plays diverse roles in the DNA damage response (DDR), in DNA repair, transcription, replication, chromatin remodelling, metabolism and cell death. In this review, we summarize the current understanding of the biology of PARylation, focusing on the functionality and the activities of the PARPs' founding member PARP1/ARTD1, which is modulated by a variety of posttranslational modifications. We also discuss the homeostasis of PAR - a process which is maintained by the balance of PAR synthesizers and erasers. We aim to sensitize the scientific community to the complexity of PAR homeostasis. Finally, we provide some perspective on how future research could try to disentangle the biology of PARylation - perhaps the most sophisticated, but still intricate posttranslational modification described to date. PMID- 27664470 TI - REV-ERBalpha Activates C/EBP Homologous Protein to Control Small Heterodimer Partner-Mediated Oscillation of Alcoholic Fatty Liver. AB - The small heterodimer partner (SHP) nuclear receptor is an important regulator of nonalcoholic fatty liver disease. However, little is known about the role of SHP in alcoholic fatty liver. In this study, we used a modified chronic ethanol-binge model to examine cyclic alterations of lipid metabolism in wild-type (WT) and Shp /- mice over a 24-hour period after binge. The serum and hepatic lipid profiles, as well as the expression of lipid synthesis genes and markers of endoplasmic reticulum stress, exhibited distinct variations in WT and Shp-/- mice in response to ethanol diet plus ethanol binge (ED+E) and control diet plus maltose binge. ED+E induced steatosis in WT mice, which correlated with a marked up-regulation of activating transcription factor 4 protein (ATF4) but down-regulation of C/EBP homologous protein (CHOP) and sterol regulatory element-binding transcription factor 1c protein (SREBP-1c). On the contrary, the control diet plus maltose binge caused lipid accumulation in Shp-/- mice, which was accompanied by a sharp elevation of CHOP, SREBP-1c, and REV-ERBalpha proteins but a diminished ATF4. REV ERBalpha activated CHOP promoter activity and gene transcription, which were inhibited by SHP. Knockdown Rev-Erbalpha in Shp-/- mice prevented steatosis induced by ED+E. Our study revealed a critical role of SHP and REV-ERBalpha in controlling rhythmic CHOP expression in alcoholic fatty liver. PMID- 27664472 TI - Future Perspectives on Pathogenesis of Lupus Nephritis: Facts, Problems, and Potential Causal Therapy Modalities. AB - Divergent incommensurable models have been developed to explain the pathogenesis of lupus nephritis. Most contemporary models favor a central role for anti chromatin antibodies. How they exert their pathogenic effect has, however, endorsed conflicts that at least for now preclude insight into definitive pathogenic pathways. The following paradigms are contemporarily in conflict with each other: i) the impact of anti-double-stranded DNA (dsDNA) antibodies that cross-react with inherent renal antigens, ii) the impact of anti-dsDNA antibodies targeting exposed chromatin in glomeruli, and iii) the impact of relative antibody avidity for dsDNA, chromatin fragments, or cross-reacting antigens. Aside from these three themes, the pathogenic role of T cells in lupus nephritis is not clear. These different models should be tested through a collaboration between scientists belonging to the different paradigms. If it turns out that there are different pathogenic pathways in lupus nephritis, the emerging pathogenic mechanism(s) may be encountered with new individual causal therapy modalities. Today, therapy is still unspecific and far from interfering with the cause(s) of the disorder. This review attempts to describe what we know about processes that may cause lupus nephritis and how such basic processes may be affected if we can specifically interrupt them. Secondary inflammatory mechanisms, cytokine signatures, activation of complement, and other contributors to inflammation will not be discussed herein; rather, the events that trigger these factors will be discussed. PMID- 27664473 TI - Distinguishing the Signals From the Noise: Can Epidemiologic Studies Inform Our Understanding of Glomerular Disease? PMID- 27664471 TI - Death Receptor 3 Promotes Chemokine-Directed Leukocyte Recruitment in Acute Resolving Inflammation and Is Essential for Pathological Development of Mesothelial Fibrosis in Chronic Disease. AB - Death receptor 3 (DR3; TNFRSF25) and its tumor necrosis factor-like ligand TL1A (TNFSF15) control several processes in inflammatory diseases through the expansion of effector T cells and the induction of proinflammatory cytokines from myeloid and innate lymphoid cells. Using wild-type (DR3+/+) and DR3-knockout (DR3 /-) mice, we show that the DR3/TL1A pathway triggers the release of multiple chemokines after acute peritoneal inflammation initiated by a single application of Staphylococcus epidermidis supernatant, correlating with the infiltration of multiple leukocyte subsets. In contrast, leukocyte infiltration was not DR3 dependent after viral challenge with murine cytomegalovirus. DR3 expression was recorded on connective tissue stroma, which provided DR3-dependent release of chemokine (C-C motif) ligand (CCL) 2, CCL7, CXCL1, and CXCL13. CCL3, CCL4, and CXCL10 production was also DR3 dependent, but quantitative RT-PCR showed that their derivation was not stromal. In vitro cultures identified resident macrophages as a DR3-dependent source of CCL3. Whether DR3 signaling could contribute to a related peritoneal pathology was then tested using multiple applications of S. epidermidis supernatant, the repetitive inflammatory episodes of which lead to peritoneal membrane thickening and collagen deposition. Unlike their DR3+/+ counterparts, DR3-/- mice did not develop fibrosis of the mesothelial layer. Thus, this work describes both a novel function and essential requirement for the DR3/TL1A pathway in acute, resolving, and chronic inflammation in the peritoneal cavity. PMID- 27664474 TI - CKD and Cardiovascular Events: Unraveling the Disparities Among Minorities. PMID- 27664475 TI - Spironolactone in Dialysis: What's Old Is New Again. PMID- 27664476 TI - Quiz Page October 2016: Severe Hypokalemia, Metabolic Alkalosis, and Malignancy. PMID- 27664477 TI - AJKD Atlas of Renal Pathology: Alport Syndrome. PMID- 27664478 TI - AJKD Atlas of Renal Pathology: Thin Basement Membrane Lesion. PMID- 27664479 TI - AJKD Atlas of Renal Pathology: Idiopathic Nodular Sclerosis. PMID- 27664480 TI - AJKD Atlas of Renal Pathology: Acute Pyelonephritis. PMID- 27664481 TI - AJKD Atlas of Renal Pathology: Chronic Pyelonephritis. PMID- 27664483 TI - Role of Regulatory T-cells in Different Clinical Expressions of Helicobacter pylori Infection. AB - Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection does not disappear and a chronic active gastritis continues if left untreated. It has been shown that the topographical pattern and immune response of gastritis are the main reasons for the bacteria persistence and the clinical outcome. Gastritis due to H. pylori is caused by a complicated interaction among a variety of T cell subsets. Regulatory T (Treg) cells suppressing the immune response of antigen-specific T-cells have recently been demonstrated to play a key role in chronic inflammation by immunologic tolerance. Treg cells have been identified as the major regulatory component of the adaptive immune response and being involved in H. pylori-related inflammation and bacterial persistence. There have been many controversies over the role of Treg cells in H. pylori infection. Many studies have shown that the local Treg response protects the gastric mucosa from intensified inflammation and tissue damage, and the risk of H. pylori-associated diseases has an inverse correlation with Treg accumulation, even if the decrease in the inflammatory response is recognized by Treg it causes increase in bacterial density. This paper reviews the role of Treg in different clinical expressions of H. pylori infection. PMID- 27664482 TI - AJKD Atlas of Renal Pathology: Malakoplakia. PMID- 27664484 TI - Opposite Function of ERalpha and ERbeta in Controlling 17beta-Estradiol-mediated Osteogenesis in Osteoblasts. AB - Estrogen receptor plays critical roles in osteogenesis but the underlying mechanism remains unclear. In order to determine the effect of ERalpha and ERbeta on several critical factors in regulating osteogenesis in human osteoblasts. Cell based assy, RT-PCR and immunoblot analyses were used in the research. Both RT-PCR and immunoblot showed that gene expression of OPG, MBP2, TGF-beta, RUNX2, IGF-1 was significantly reduced while expression of RANKL was drastically increased after shRNA-based depletion of ERalpha in MG-63 osteoblasts. Surprisingly, 17beta estradiol (E2) treatment led to remarkably reduced RANKL compared with that in E2 untreated cells. In contrast, ERbeta plays an opposite role in regulating gene expression of OPG, MBP2, TGF-beta, RUNX2, IGF-1 and RANKL. However, double depletion of ERalpha and ERbeta could not rescue the gene expression of these factors in vitro. Our results provide a novel mechanism of estrogen receptor in controlling osteogenesis in human cells as well as a potential clinic therapeutic target in human osteoporosis. PMID- 27664485 TI - Efficacious In Vitro and In Vivo Effects of Dihydrosphingosine-Ethambutol Analogues Against Susceptible and Multi-drug-resistant Mycobacterium tuberculosis. AB - BACKGROUND AND AIMS: Tuberculosis (TB) is a major worldwide health problem in part due to the lack of new drugs and the emergence of multidrug-resistant strains (MDR). The aim of this study was to select anti-tuberculosis drug candidates from a collection of 69 synthetic sphingosine-ethambutol analogues through in vitro and in vivo evaluations. METHODS: The 69 compounds were evaluated in vitro against two Mycobacterium tuberculosis strains, a drug susceptible (H37Rv) and a MDR clinical isolate (CIBIN-99). Four selected compounds, those that exhibited the highest potency in vitro, were tested in vivo using a model of progressive TB in BALB/c mice infected with the drug susceptible strain, either alone or combined with conventional chemotherapy, as well as in mice infected with the MDR strain. The acute toxicity was evaluated on male and female adult BALB/c mice. RESULTS: Ten of the evaluated compounds resulted more potent in vitro than ethambutol. The experimental compound 2b (2-aminopalmitol benzyl ether) was the most efficacious and also showed additive effects in combination with conventional chemotherapy. It did not exhibit toxicity (LD50 >2000 mg/kg). CONCLUSIONS: Compound 2b can be considered as a new drug candidate to continue its development against M. tuberculosis MDR strains. PMID- 27664486 TI - Tumor Growth and Cell Proliferation Rate in Human Oral Cancer. AB - BACKGROUND AND AIMS: Oral squamous cell cancer (SCC) has a high rate of morbidity and an overall 5-year survival rate for patients of 50%, statistics that have not changed in the last half century. A better understanding of the biological nature of this aggressive disease is mandatory. The two most studied human oral cancer cell lines-SCC-15 and SCC-25-share some biological characteristics but differ in others and may serve as a platform for further oral SCC analysis. We compared their basic carcinogenic characteristics, cellular proliferation rate and tumor growth, and discussed results according to available data from the literature and our own previous studies. METHODS: We examined doubling time both in vitro and in vivo of the SCC-15 and SCC-25 cell lines. After seeding the exact same number of cells in a six-well dish we counted them daily. To confirm doubling time differences in cells, we progressed to an in vivo model in nude mice using male 9 to 10-week-old BALB/c-nu/nu mice. RESULTS: In both models (in vitro and in vivo) SCC-15 multiplied faster than SCC-25 cell line. In vivo the difference was more than double and in vitro this change was 24%. CONCLUSION: Both SCC-15 and SCC-25 cell lines are suitable for further exploration of the oral carcinogenesis process. Based on our currently presented results and on the available literature, it seems that SCC-15 has an increased potential for local tumor growth and cell proliferation, whereas SCC-25 has a higher potential for invasion and metastasis. PMID- 27664487 TI - Budesonide Attenuates Ventilator-induced Lung Injury in a Rat Model of Inflammatory Acute Respiratory Distress Syndrome. AB - BACKGROUND AND AIMS: Patients with acute respiratory distress syndrome (ARDS) are particularly susceptible to ventilator-induced lung injury (VILI). This study investigated the effect of budesonide on VILI in a rat model of inflammatory ARDS. METHODS: Forty eight rats were randomized into three groups (n = 16 each): sham group (S), endotoxin/ventilation group (LV), endotoxin/ventilation/budesonide group (LVB). Rats in the S group received anesthesia only. Rats in the LV and LVB groups received endotoxin to simulate ARDS and were mechanically ventilated for 4 h (tidal volume 30 mL/kg). Rats in the LVB group received budesonide 1 mg, and rats in the LV group received saline in airway. PaO2/FiO2, lung wet-to-dry weight ratios, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), histopathologic analysis of lung tissue, and survival were examined. RESULTS: PaO2/FiO2 was significantly increased in rats in the LVB group compared to the LV group. Total cell count, macrophages, and neutrophils in BALF, and levels of intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 in BALF and serum were significantly decreased in rats in the LVB group compared to the LV group, whereas levels of IL-10 in BALF and serum were significantly increased. Histopathological changes of lung injury and apoptosis were reduced, and survival was increased in rats in the LVB group compared to the LV group. CONCLUSIONS: Budesonide ameliorated VILI in a rat model of inflammatory ARDS. PMID- 27664488 TI - Site-specific Hypermethylation of RUNX3 Predicts Poor Prognosis in Gastric Cancer. AB - BACKGROUND AND AIMS: Methylation status of RUNX3 remains largely unknown in gastric cancer (GC). The aim of this study was to prognostically evaluate the methylation level of CpG sites within RUNX3 promoter region in GC. METHODS: Using pyrosequencing, we quantitatively explored the methylation status of 8 CpG sites within RUNX3 promoter region for 76 gastric cancer and 24 normal gastric tissues. We then analyzed the association between methylation level of each CpG site and clinicopathological characteristics and outcomes in the cohort. RESULTS: Methylation of RUNX3 promoter was significantly higher in GC than normal subjects. Overall methylation level was closely associated with tumor invasion and TNM stage. Positive associations were found between hypermethylation of the following concerned sites and variables: site -1392, -1397, -1403, -1415 and tumor invasion, as well as TNM stage; site -1392 and lymph node metastasis along with number of lymph node metastases; site -1415 and cancer recurrence; site 1403, -1415 and cancer-related deaths. In multivariate analysis, tumor invasion was correlated with sites -1392 and -1397. Lymph node metastasis was associated with site -1392. Most importantly, methylation of site -1415 was associated with poor survival by using Cox survival regression. CONCLUSION: Analysis of RUNX3 gene promoter by quantitative pyrosequencing suggested methylation status of RUNX3 is different in normal and tumor tissues. RUNX3 methylation level is associated with GC, especially the methylation at site -1415 contributes to the poor prognosis in GC. Thus, RUNX3 methylation may serve as a valuable diagnostic and prognostic biomarker in GC. PMID- 27664489 TI - Novel Multiplex Fluorescent PCR-Based Method for HLA Typing and Preimplantational Genetic Diagnosis of beta-Thalassemia. AB - BACKGROUND AND AIMS: Thalassemia is curable by bone marrow transplantation; however, finding suitable donors with defined HLA combination remains a major challenge. Cord blood stem cells with preselected HLA system through preimplantation genetic diagnosis (PGD) proved very useful for resolving scarce HLA-matched bone marrow donors. METHODS: A thalassemia trait couple with an affected child was included in this study. We used informative STR markers at the HLA and beta globin loci to develop a single cell multiplex fluorescent PCR protocol. The protocol was extensively optimized on single lymphocytes isolated from the couple's peripheral blood. The optimized protocol was applied on single blastomeres biopsied from day 3 cleavage stage IVF embryos of the couple. RESULTS: Four IVF embryos biopsied on day 3 and a single blastomere of each were provided for genetic diagnosis of combined beta-thalassemia mutations and HLA typing. Of these, one embryo was diagnosed as homozygous normal for the thalassemia mutation and HLA matched with the existing affected sibling. CONCLUSION: The optimized protocol worked well in PGD clinical cycle for selection of thalassemia-unaffected embryos with the desired HLA system. PMID- 27664490 TI - Prognostic Significance of Serum CD26 Concentration in Patients with Esophageal Squamous Cell Carcinoma. AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in developing countries. The aim of the study was to determine the association between serum CD26 concentration and outcome of patients with ESCC. METHODS: A total of 183 patients with ESCC and 254 healthy controls were selected. Blood samples were obtained from the participants. The serum level of CD26 was detected using a commercial enzyme-linked immunosorbent assay kit. All patients were followed for 4 years unless they died of ESCC during the follow-up period. RESULTS: Compared with the controls, serum CD26 levels in the patients decreased at admission (p <0.001), recovered to normal 1 month after resection (p = 0.087), and declined again at the time of tumor relapse (p <0.001). During the follow-up period, 107 patients died of ESCC and 76 patients survived. Multivariate logistic regression analysis revealed that the low serum level of CD26 (<530 pg/mL) was associated with poor prognosis in the patients (OR: 5.42, 95% CI: 2.91-8.41). Survival analysis also suggested that the patients with high serum level of CD26 (>=530 pg/mL) had a survival advantage compared with the patients with low serum level of CD26 (<530 pg/mL) (p <0.001). CONCLUSIONS: Serum CD26 concentration might be an independent prognostic indicator in patients with ESCC. It might be also useful to detect recurrent tumor in postoperative patients. PMID- 27664491 TI - Resveratrol Supplementation and Oxidative/Anti-Oxidative Status in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. AB - BACKGROUND AND AIMS: Oxidative stress is involved in both pathogenesis and exacerbation of ulcerative colitis (UC). This study was designed to evaluate whether resveratrol, an excellent anti-oxidant agent, can help in treatment of UC and its related oxidative stress. METHODS AND RESULTS: Fifty six patients with active mild to moderate disease were randomized to receive either 500 mg/day resveratrol capsules or the same amount of placebo for 6 weeks. Before and after the intervention, disease activity, quality of life, and oxidative stress were assessed using the Simple Clinical Colitis Activity Index Questionnaire (SCCAIQ), Inflammatory Bowel Disease Questionnaire-9 (IBDQ-9), and serum level of malondialdehyde (MDA), superoxide dismutase (SOD), and total anti-oxidant capacity (TAC), respectively. Serum SOD (122.28 +/- 11.55 to 125.77 +/- 10.97) and TAC (9.87 +/- 1.51-11.97 +/- 1.61) increased, whereas serum MDA (5.62 +/- 1.18-3.42 +/- 1.01) decreased significantly in resveratrol group (p <0.001). Moreover, resveratrol supplementation significantly decreased disease activity and increased the quality of life (p <0.001). CONCLUSION: Our data indicate that 500 mg/day resveratrol supplementation can improve the disease activity and quality of life in patients with UC at least partially through reduction of oxidative stress. Further studies are needed to determine the optimal dosage of supplementation for these patients. PMID- 27664492 TI - Low Thyroid Stimulating Hormone Levels Are Associated with Low Bone Mineral Density in Femoral Neck in Elderly Women. AB - BACKGROUND AND AIMS: To determine the relationship between thyroid stimulating hormone (TSH) and bone mineral density (BMD) in elderly women. METHODS: This is a retrospective cross-sectional population cohort study of women aged >=65 years. All 1097 subjects had no overt thyroid dysfunction, 47 had subclinical hyperthyroidism and 100 had subclinical hypothyroidism. Overall, 167 had normal BMD, 594 had osteopenia and 336 had osteoporosis. RESULTS: The femoral neck (FN) BMD was lower in women with lower TSH, with a high prevalance of osteoporosis and osteopenia (p = 0.036).The prevalence of osteoporosis and osteopenia was significantly low in the lowest quartile compared with the third quartile (p = 0.023) and the fourth quartile (p = 0.002), and the second low quartile, compared with the fourth quartile (p = 0.028). The differences were not significant among subclinical hyperthyroid, subclinical hypothyroid and euthyroid women. Low TSH was related to low BMDs at FN by multiple logistic regression analysis corrected for age and BMI. TSH in the lower two quartiles were independently related to osteoporosis (OR: 1.960, p = 0.023 and OR: 1.800, p = 0.037) and osteopenia (OR: 2.108, p = 0.005 and OR: 1.723, p = 0.030). Low TSH quartile (beta: 0.007, p = 0.013) predicting low BMDs at FN. CONCLUSION: Low TSH was independently related to decreased BMDs at FN in elderly women without overt thyroid dysfunction. PMID- 27664493 TI - Association of rs1122608 with Coronary Artery Disease and Lipid Profile: A Meta analysis. AB - BACKGROUND AND AIMS: It has been reported that rs1122608 adjacent to low-density lipoprotein cholesterol receptor (LDLR) locus is associated with the risk of coronary artery disease (CAD) and blood lipid profile in the Caucasian population. Due to the contradictory results in the Asian population, we conducted a meta-analysis to systematically summarize and clarify the association between rs1122608 with CAD risk and lipid profile. METHODS: A systematic search regarding studies on the association of rs1122608 with CAD risk and lipid profile was conducted in databases including PubMed, Embase, and Cochrane library. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. RESULTS: A total of five case-control studies were included in this study. A statistically significant association was identified between rs1122608-G allele and CAD risk in overall analysis (OR = 2.09, 95% CI 1.48-2.97) and in both Asian (OR = 1.82, 95% CI 1.04-3.18) and Caucasian subgroups (OR = 2.31, 95% CI 1.48 3.60). The rs1122608-G allele was associated with increased triglyceride (TG) level (OR = 1.25, 95% CI 1.03-1.52), but not with total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), or LDL cholesterol level. Moreover, the rs1122608-G allele is associated with increased CAD risk in the Asian male population (OR = 3.37, 95% CI 1.51-9.86) but not in the Asian female population. CONCLUSIONS: The rs1122608 is associated with the risk of CAD and TG level. The rs1122608-G allele was a significant risk factor of CAD in the Asian male population but not in the Asian female population. PMID- 27664494 TI - Clinical Importance of Pentraxin 3 in Autoimmune Diseases. PMID- 27664495 TI - Response: Clinical Importance of Pentraxin 3 in Autoimmune Diseases. PMID- 27664497 TI - From birth plan to birth partnership: enhancing communication in childbirth. AB - Birth plans were developed with the intention of enhancing a woman's prepared decision-making in the labor and delivery process and to offer obstetric care providers with important details about those decisions. Through the use of birth plans, women can reflect on their values and choices regarding what care practices and interventions they do and do not want in birth; they can communicate these values in advance to their care providers. However, birth plans are often ineffective at accomplishing their goals for a number of reasons. They may reflect outdated concerns about routine practices or overly emphasize minor matters. Many popular pregnancy websites offer birth plans that use checklist formats, and women who use these are not counseled about which options may require or preclude other options. Some women may have inappropriately rosy expectations of how their labor and delivery processes will progress or have received poor advice. The use of a birth plan may invoke hostility from hospital staff members who may disregard the plans and look down on the women who make them. An alternative approach to the use of birth plans to enhance a woman's participation and informed consent in the birth process is the birth partnership, in which women and their obstetric care providers take time to discuss thoroughly the choices to be made in birth in advance to have those choices best reflect the values of the woman giving birth. Meeting to discuss values and choices before labor offers the opportunity for mutual education between provider and patient about the choices to be made and the values that inform those choices. Effective communication and working to build mutual trust can serve as preventive measures to avoid many conflicts that arise in the birth process. PMID- 27664496 TI - All the darkness we don't see. AB - Trafficking of women and children for sexual exploitation is the fastest growing criminal enterprise in the world. This is a public health crisis; as physicians who have direct contact with victims, we have a unique opportunity to intervene. The authors developed a specialty clinic for survivors of sex trafficking in 2013 at an academic medical center in New York City. Twenty of the 24 women seen in the Survivor Clinic saw a physician while being trafficked. Sex trafficking violates basic human rights, which include the rights to bodily integrity, dignity, health, and freedom from violence and torture. The stories of the patients seen in the Survivor Clinic bear witness to the health consequences of commercial sexual exploitation and reinforce the previous literature on the rates of physical and psychologic harms of trafficking. Health consequences of trafficking include traumatic brain injuries, drug addiction, depression, and neglect of chronic health conditions. All physicians, but gynecologists especially, need more education about the prevalence and dynamics of trafficking and how to assess and intervene on behalf of survivors. PMID- 27664498 TI - Enhancement of liposome mediated gene transfer by adding cholesterol and cholesterol modulating drugs. AB - Cholesterol is an important cell membrane component and has been used as co-lipid for cationic liposome to enhance gene delivery. However, the role of cholesterol in transfection efficiency has not been fully understood. In this study, transfection efficiency of liposome was measured after cholesterol was added to the cell culture medium. As a result, addition of cholesterol increased transfection efficiency of several liposomes consisting of different lipid components in various cells (AGS, CHO, COS7 and, MCF7). Furthermore, treatment of cells with cholesterol modulating drugs, imipramine and U18666A, also increased transfection efficiency of liposomes. To elucidate the role of added cholesterol in gene transfer, endocytotic mechanism was studied and also revealed that adding cholesterol in culture media induced participation of caveolae-mediated endocytosis and micropinocytosis in CHO cell. Therefore, the results of this work suggest that modulation of intracellular cholesterol can be an important method to enhance gene delivery. PMID- 27664500 TI - Mixed DPPC/POPC Monolayers: All-atom Molecular Dynamics Simulations and Langmuir Monolayer Experiments. AB - To elucidate the consequences of the saturated-unsaturated nature of lipid surface films, monolayers formed by an equimolar mixture of 1-palmitoyl-2-oleyl sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC) lipids are investigated in a wide range of surface pressures. As such mixtures share some features with naturally-occurring surfactants, for example the lung surfactant, the systems are studied at the temperature relevant for human body. All-atom molecular dynamics simulations and Langmuir trough experiments are employed. The binary lipid mixture is compared with the corresponding one-component systems. Atomistic-level alterations of monolayer molecular properties upon lateral compression are scrutinized. These involve elevation of lateral ordering of lipid chains, modulation of chain and headgroup orientation, and reduction of lipid hydration. The presence of the unsaturated POPC in the DPPC/POPC mixture reduces the liquid expanded-liquid condensed coexistence region and moderates the phase transition. Simulations predict that nanoscale lipid de-mixing occurs with small transient DPPC clusters emerging due to local fluctuations of the lateral lipid arrangement. A vertical sorting of lipids induced by lateral compression is also observed, with DPPC transferred toward the water phase. Both the conformational lipid alterations due to monolayer compression as well as the existence of lateral dynamic inhomogeneities of the lipid film are potentially pertain to dynamic and non homogeneous lipid interfacial systems. PMID- 27664499 TI - Stability of an amphipathic helix-hairpin surfactant peptide in liposomes. AB - Surfactant protein B (SP-B; 79 residues) is a member of the saposin superfamily and plays a pivotal role in lung function. The N- and C-terminal regions of SP-B, cross-linked by two disulfides, were theoretically predicted to fold as charged amphipathic helices, suggesting participation in surfactant activities. Previous studies with oxidized Super Mini-B (SMB), a construct based on the N- and C regions of SP-B (i.e., residues 1-25 and 63-78) joined with a designer turn ( PKGG-) and two disulfides, indicated that freshly prepared SMB in lipids folded as a surface active, alpha-helix-hairpin. Because other peptides modeled on alpha helical SP domains lost helicity and surfactant activity on storage, experiments were here performed on oxidized SMB in surfactant liposomes stored at ~2-8 degrees C for <=5.5years. Captive bubble surfactometry confirmed low minimum surface tensions for fresh and stored SMB preparations. FTIR spectroscopy of fresh and stored SMB formulations showed secondary structures compatible with the peptide folding as alpha-helix-hairpin. A homology (I-TASSER) model of oxidized SMB demonstrated a globular protein, exhibiting a core of hydrophobic residues and a surface of polar residues. Since mass spectroscopy indicated that the disulfides were maintained on storage, the stability of SMB may be partly due to the disulfides bringing the N- and C-alpha-helices closer. Mass spectroscopy of stored SMB preparations showed some methionine oxidation, and also partial deacylation of surfactant phospholipids to form lyso-derivatives. However, the stable conformation and activity of stored SMB surfactant suggest that the active helix-hairpin resists these chemical changes which otherwise may lead to surfactant inhibition. PMID- 27664501 TI - DMSO-induced perturbation of thermotropic properties of cholesterol-containing DPPC liposomes. AB - Dimethyl sulfoxide (DMSO) is a universal solvent widely used in many fields, from basic research to industrial applications. At low concentration, it is the most important cryoprotectant agent against cellular damage caused during a freeze thaw cycle. Although the effects of this cosolvent on the physico-chemical properties of a lipid bilayer have been extensively studied with both in vitro and in vivo experiments, the molecular mechanism of cryopreservation is not completely understood. Cholesterol (Chol) represents one of the essential cell membrane component and is fundamental to maintain the integrity and fluidity of the membrane. Here we report a study on the effect of DMSO on the stability of Chol-containing model membranes. We investigated the effect of DMSO on thermal stability of model membranes formed by dipalmitoylphospatidylcholine (DPPC) and DPPC/Chol by means of Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) measurements. It is well known that cholesterol reduces the thermal stability of DPPC vesicles and also the pre transition is abolished. Our results show that DMSO induces a stabilization of the lipid bilayer of DPPC liposomes increasing both the pre- and main transition temperatures. In DPPC/Chol liposomes a similar thermal stabilization was observed for the main transition indicating that DMSO is capable to stabilize the lipid bilayer even in the presence of the sterol. Moreover, by direct inspection of the hydration degree of the lipid bilayers, we evidenced the role played by DMSO on the thermal stability of the membrane as connected to the hydration of the polar head groups. PMID- 27664502 TI - An extensive simulation study of lipid bilayer properties with different head groups, acyl chain lengths, and chain saturations. AB - Previous MD simulations of six phosphocholine (PC) lipid bilayers demonstrated the accuracy of the CHARMM36 force field (C36FF) for PC bilayer simulation at varied temperatures (BBA-Biomembranes, 1838 (2014): 2520-2529). In this work, we further examine the accuracy of C36FF over a wide temperature range for a broader range of lipid types such as various head groups (phosphatidic acid (PA), PC, phosphoethanolamine (PE), phosphoglycerol (PG), and phosphoserine (PS)), and tails (saturated, mono-, mixed- and poly-unsaturated acyl chains with varied chain lengths). The structural properties (surface area per lipid (SA/lip), overall bilayer thickness, hydrophobic thickness, headgroup-to-headgroup thickness, deuterium order parameter (SCD), and spin-lattice relaxation time (T1)) obtained from simulations agree well with nearly all available experimental data. Our analyses indicate that PS lipids have the most inter-lipid hydrogen bonds, while PG lipids have the most intra-lipid hydrogen bonds, which play the main role in their low SA/lip in PS lipids and low thicknesses in PG lipids, respectively. PS, PE, and PA lipids have the largest contact clusters with on average 5-8 lipids per cluster, while PC and PG have clusters of 4 lipids based on a cutoff distance of 6.5A. PS lipids have much slower lipid wobble (i.e., higher correlation time) than other head groups at a given temperature as the hydrogen bonded network significantly reduces a lipid's mobility, and the rate of lipid wobble increases dramatically as temperature increases. These in-depth analyses facilitate further understanding of lipid bilayers at the atomic level. PMID- 27664503 TI - 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). PMID- 27664504 TI - Survival analysis for high-dimensional, heterogeneous medical data: Exploring feature extraction as an alternative to feature selection. AB - BACKGROUND: In clinical research, the primary interest is often the time until occurrence of an adverse event, i.e., survival analysis. Its application to electronic health records is challenging for two main reasons: (1) patient records are comprised of high-dimensional feature vectors, and (2) feature vectors are a mix of categorical and real-valued features, which implies varying statistical properties among features. To learn from high-dimensional data, researchers can choose from a wide range of methods in the fields of feature selection and feature extraction. Whereas feature selection is well studied, little work focused on utilizing feature extraction techniques for survival analysis. RESULTS: We investigate how well feature extraction methods can deal with features having varying statistical properties. In particular, we consider multiview spectral embedding algorithms, which specifically have been developed for these situations. We propose to use random survival forests to accurately determine local neighborhood relations from right censored survival data. We evaluated 10 combinations of feature extraction methods and 6 survival models with and without intrinsic feature selection in the context of survival analysis on 3 clinical datasets. Our results demonstrate that for small sample sizes - less than 500 patients - models with built-in feature selection (Cox model with l1 penalty, random survival forest, and gradient boosted models) outperform feature extraction methods by a median margin of 6.3% in concordance index (inter quartile range: [-1.2%;14.6%]). CONCLUSIONS: If the number of samples is insufficient, feature extraction methods are unable to reliably identify the underlying manifold, which makes them of limited use in these situations. For large sample sizes - in our experiments, 2500 samples or more - feature extraction methods perform as well as feature selection methods. PMID- 27664505 TI - Building interpretable predictive models for pediatric hospital readmission using Tree-Lasso logistic regression. AB - OBJECTIVES: Quantification and early identification of unplanned readmission risk have the potential to improve the quality of care during hospitalization and after discharge. However, high dimensionality, sparsity, and class imbalance of electronic health data and the complexity of risk quantification, challenge the development of accurate predictive models. Predictive models require a certain level of interpretability in order to be applicable in real settings and create actionable insights. This paper aims to develop accurate and interpretable predictive models for readmission in a general pediatric patient population, by integrating a data-driven model (sparse logistic regression) and domain knowledge based on the international classification of diseases 9th-revision clinical modification (ICD-9-CM) hierarchy of diseases. Additionally, we propose a way to quantify the interpretability of a model and inspect the stability of alternative solutions. MATERIALS AND METHODS: The analysis was conducted on >66,000 pediatric hospital discharge records from California, State Inpatient Databases, Healthcare Cost and Utilization Project between 2009 and 2011. We incorporated domain knowledge based on the ICD-9-CM hierarchy in a data driven, Tree-Lasso regularized logistic regression model, providing the framework for model interpretation. This approach was compared with traditional Lasso logistic regression resulting in models that are easier to interpret by fewer high-level diagnoses, with comparable prediction accuracy. RESULTS: The results revealed that the use of a Tree-Lasso model was as competitive in terms of accuracy (measured by area under the receiver operating characteristic curve-AUC) as the traditional Lasso logistic regression, but integration with the ICD-9-CM hierarchy of diseases provided more interpretable models in terms of high-level diagnoses. Additionally, interpretations of models are in accordance with existing medical understanding of pediatric readmission. Best performing models have similar performances reaching AUC values 0.783 and 0.779 for traditional Lasso and Tree-Lasso, respectfully. However, information loss of Lasso models is 0.35 bits higher compared to Tree-Lasso model. CONCLUSIONS: We propose a method for building predictive models applicable for the detection of readmission risk based on Electronic Health records. Integration of domain knowledge (in the form of ICD-9-CM taxonomy) and a data-driven, sparse predictive algorithm (Tree-Lasso Logistic Regression) resulted in an increase of interpretability of the resulting model. The models are interpreted for the readmission prediction problem in general pediatric population in California, as well as several important subpopulations, and the interpretations of models comply with existing medical understanding of pediatric readmission. Finally, quantitative assessment of the interpretability of the models is given, that is beyond simple counts of selected low-level features. PMID- 27664506 TI - META-GLARE: A meta-system for defining your own computer interpretable guideline system-Architecture and acquisition. AB - CONTEXT: Several different computer-assisted management systems of computer interpretable guidelines (CIGs) have been developed by the Artificial Intelligence in Medicine community. Each CIG system is characterized by a specific formalism to represent CIGs, and usually provides a manager to acquire, consult and execute them. Though there are several commonalities between most formalisms in the literature, each formalism has its own peculiarities. OBJECTIVE: The goal of our work is to provide a flexible support to the extension or definition of CIGs formalisms, and of their acquisition and execution engines. Instead of defining "yet another CIG formalism and its manager", we propose META GLARE (META Guideline Acquisition, Representation, and Execution), a "meta" system to define new CIG systems. METHOD AND MATERIALS: In this paper, META GLARE, a meta-system to define new CIG systems, is presented. We try to capture the commonalities among current CIG approaches, by providing (i) a general manager for the acquisition, consultation and execution of hierarchical graphs (representing the control flow of actions in CIGs), parameterized over the types of nodes and of arcs constituting it, and (ii) a library of different elementary components of guidelines nodes (actions) and arcs, in which each type definition involves the specification of how objects of this type can be acquired, consulted and executed. We provide generality and flexibility, by allowing free aggregations of such elementary components to define new primitive node and arc types. RESULTS: We have drawn several experiments, in which we have used META GLARE to build a CIG system (Experiment 1 in Section 8), or to extend it (Experiments 2 and 3). Such experiments show that META-GLARE provides a useful and easy-to-use support to such tasks. For instance, re-building the Guideline Acquisition, Representation, and Execution (GLARE) system using META-GLARE required less than one day (Experiment 1). CONCLUSIONS: META-GLARE is a meta system for CIGs supporting fast prototyping. Since META-GLARE provides acquisition and execution engines that are parametric over the specific CIG formalism, it supports easy update and construction of CIG systems. PMID- 27664507 TI - Prediction of lung cancer incidence on the low-dose computed tomography arm of the National Lung Screening Trial: A dynamic Bayesian network. AB - INTRODUCTION: Identifying high-risk lung cancer individuals at an early disease stage is the most effective way of improving survival. The landmark National Lung Screening Trial (NLST) demonstrated the utility of low-dose computed tomography (LDCT) imaging to reduce mortality (relative to X-ray screening). As a result of the NLST and other studies, imaging-based lung cancer screening programs are now being implemented. However, LDCT interpretation results in a high number of false positives. A set of dynamic Bayesian networks (DBN) were designed and evaluated to provide insight into how longitudinal data can be used to help inform lung cancer screening decisions. METHODS: The LDCT arm of the NLST dataset was used to build and explore five DBNs for high-risk individuals. Three of these DBNs were built using a backward construction process, and two using structure learning methods. All models employ demographics, smoking status, cancer history, family lung cancer history, exposure risk factors, comorbidities related to lung cancer, and LDCT screening outcome information. Given the uncertainty arising from lung cancer screening, a cancer state-space model based on lung cancer staging was utilized to characterize the cancer status of an individual over time. The models were evaluated on balanced training and test sets of cancer and non-cancer cases to deal with data imbalance and overfitting. RESULTS: Results were comparable to expert decisions. The average area under the curve (AUC) of the receiver operating characteristic (ROC) for the three intervention points of the NLST trial was higher than 0.75 for all models. Evaluation of the models on the complete LDCT arm of the NLST dataset (N=25,486) demonstrated satisfactory generalization. Consensus of predictions over similar cases is reported in concordance statistics between the models' and the physicians' predictions. The models' predictive ability with respect to missing data was also evaluated with the sample of cases that missed the second screening exam of the trial (N=417). The DBNs outperformed comparison models such as logistic regression and naive Bayes. CONCLUSION: The lung cancer screening DBNs demonstrated high discrimination and predictive power with the majority of cancer and non-cancer cases. PMID- 27664508 TI - Efficient processing of multiple nested event pattern queries over multi dimensional event streams based on a triaxial hierarchical model. AB - OBJECTIVE: For efficient and sophisticated analysis of complex event patterns that appear in streams of big data from health care information systems and support for decision-making, a triaxial hierarchical model is proposed in this paper. METHODS AND MATERIAL: Our triaxial hierarchical model is developed by focusing on hierarchies among nested event pattern queries with an event concept hierarchy, thereby allowing us to identify the relationships among the expressions and sub-expressions of the queries extensively. We devise a cost based heuristic by means of the triaxial hierarchical model to find an optimised query execution plan in terms of the costs of both the operators and the communications between them. According to the triaxial hierarchical model, we can also calculate how to reuse the results of the common sub-expressions in multiple queries. By integrating the optimised query execution plan with the reuse schemes, a multi-query optimisation strategy is developed to accomplish efficient processing of multiple nested event pattern queries. RESULTS: We present empirical studies in which the performance of multi-query optimisation strategy was examined under various stream input rates and workloads. Specifically, the workloads of pattern queries can be used for supporting monitoring patients' conditions. On the other hand, experiments with varying input rates of streams can correspond to changes of the numbers of patients that a system should manage, whereas burst input rates can correspond to changes of rushes of patients to be taken care of. The experimental results have shown that, in Workload 1, our proposal can improve about 4 and 2 times throughput comparing with the relative works, respectively; in Workload 2, our proposal can improve about 3 and 2 times throughput comparing with the relative works, respectively; in Workload 3, our proposal can improve about 6 times throughput comparing with the relative work. CONCLUSION: The experimental results demonstrated that our proposal was able to process complex queries efficiently which can support health information systems and further decision-making. PMID- 27664509 TI - A mixed-ensemble model for hospital readmission. AB - OBJECTIVE: A hospital readmission is defined as an admission to a hospital within a certain time frame, typically thirty days, following a previous discharge, either to the same or to a different hospital. Because most patients are not readmitted, the readmission classification problem is highly imbalanced. MATERIALS AND METHODS: We developed a hospital readmission predictive model, which enables controlling the tradeoff between reasoning transparency and predictive accuracy, by taking into account the unique characteristics of the learned database. A boosted C5.0 tree, as the base classifier, was ensembled with a support vector machine (SVM), as a secondary classifier. The models were induced and validated using anonymized administrative records of 20,321 inpatient admissions, of 4840 Congestive Heart Failure (CHF) patients, at the Veterans Health Administration (VHA) hospitals in Pittsburgh, from fiscal years (FY) 2006 through 2014. RESULTS: The SVM predictions are characterized by greater sensitivity values (true positive rates) than are the C5.0 predictions, for a wider range of cut off values of the ROC curve, depending on a predefined confidence threshold for the base C5.0 classifier. The total accuracy for the ensemble ranges from 81% to 85%. Different predictors, including comorbidities, lab values, and vitals, play different roles in the two models. CONCLUSIONS: The mixed-ensemble model enables easy and fast exploratory knowledge discovery of the database, and a control of the classification error for positive readmission instances. Implementation of this ensembling method for predicting all-cause hospital readmissions of CHF patients allows overcoming some of the limitations of the classifiers considered individually, and of other traditional ensembling methods. It also increases the classification accuracy for positive readmission instances, particularly when strong predictors are not available. PMID- 27664510 TI - Quality of Life Research: More Than Ever. PMID- 27664513 TI - Editorial Comment. PMID- 27664511 TI - Symptoms and Signs of Heart Failure at Admission and Discharge and Outcomes in the Sub-Saharan Acute Heart Failure (THESUS-HF) Registry. AB - BACKGROUND: Symptoms and signs of heart failure (HF) are the most common reasons for admission to hospital for acute HF (AHF) and are used routinely throughout admission to assess the severity of disease and response to therapy. METHODS AND RESULTS: The data were collected in The Sub-Saharan Africa Survey on Heart Failure (THESUS-HF) study, a prospective, multicenter, observational survey of AHF from 9 countries in sub-Saharan Africa. A total of 1006 patients, >=12 years of age, hospitalized for AHF were recruited. Symptoms and signs of HF and changes in dyspnea and well-being, relative to admission, were assessed at entry and on days 1, 2, and 7 (or on discharge if earlier) and included oxygen saturation, degree of edema and rales, body weight, and level of orthopnea. The patient determined dyspnea and general well-being, whereas the physician determined symptoms and signs of HF, as well as improvements in vital sign measurement, throughout the admission. After multivariable adjustment, baseline rales and changes to day 7 or discharge in general well-being predicted death or HF hospitalization through day 60, and baseline orthopnea, edema, rales, oxygen saturation, and changes to day 7 or on discharge in respiratory rate and general well-being were predictive of death through day 180. CONCLUSIONS: In AHF patients in sub-Saharan Africa, symptoms and signs of HF improve throughout admission, and simple assessments, including edema, rales, oxygen saturation, respiratory rate, and asking the patient about general well-being, are valuable tools in patients' clinical assessment. PMID- 27664512 TI - Submucosal Tunneling Endoscopic Septum Division: A Novel Technique for Treating Zenker's Diverticulum. PMID- 27664514 TI - Editorial Comment. PMID- 27664515 TI - Zinc availability during germline development impacts embryo viability in Caenorhabditis elegans. AB - Zinc is an essential metal that serves as a cofactor in a variety of cellular processes, including meiotic maturation. Cellular control of zinc uptake, availability and efflux is closely linked to meiotic progression in rodent and primate reproduction where large fluctuations in zinc levels are critical at several steps in the oocyte-to-embryo transition. Despite these well-documented roles of zinc fluxes during meiosis, only a few of the genes encoding key zinc receptors, membrane-spanning transporters, and downstream signaling pathway factors have been identified to date. Furthermore, little is known about analogous roles for zinc fluxes in the context of a whole organism. Here, we evaluate whether zinc availability regulates germline development and oocyte viability in the nematode Caenorhabditis elegans, an experimentally flexible model organism. We find that similar to mammals, mild zinc limitation in C. elegans profoundly impacts the reproductive axis: the brood size is significantly reduced under conditions of zinc limitation where other physiological functions are not perturbed. Zinc limitation in this organism has a more pronounced impact on oocytes than sperm and this leads to the decrease in viable embryo production. Moreover, acute zinc limitation of isolated zygotes prevents extrusion of the second polar body during meiosis and leads to aneuploid embryos. Thus, the zinc dependent steps in C. elegans gametogenesis roughly parallel those described in meiotic-to-mitotic transitions in mammals. PMID- 27664516 TI - Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice. AB - Excessive bone resorption by osteoclasts plays an important role in osteoporosis. Bone loss occurs in ovariectomised (OVX) mice in a similar manner to that in humans, so this model is suitable for evaluating potential new therapies for osteoporosis. Neohesperidin (NE) is a flavonoid compound isolated from citrus fruits. Its role in bone metabolism is unknown. In this study we found that neohesperidin inhibits osteoclast differentiation, bone resorption and the expression of osteoclast marker genes, tartrate-resistant acid phosphatase and cathepsin K. In addition, neohesperidin inhibited receptor activator of NF-kappaB ligand (RANKL)-induced activation of NF-kappaB, and the degradation of inhibitor of kappa B-alpha (IkappaBalpha). Furthermore, neohesperidin inhibited RANKL induction of nuclear factor of activated T-cells (NFAT) and calcium oscillations. In vivo treatment of ovariectomised mice with neohesperidin protected against bone loss in mice. The results suggest neohesperidin has anti-osteoclastic effects in vitro and in vivo and possesses therapeutic potential as a natural anti-catabolic treatment in osteoporosis. PMID- 27664517 TI - The metabolic fate and receptor interaction of 16alpha-hydroxyprogesterone and its 5alpha-reduced metabolite, 16alpha-hydroxy-dihydroprogesterone. AB - 16alpha-hydroxyprogesterone (16OHP4) is not well characterised in terms of metabolism and receptor interaction. We therefore investigated its metabolism by adrenal CYP11B and peripheral steroidogenic enzymes, SRD5A and AKR1C2. UHPLC MS/MS analyses identified novel steroids: the biosynthesis of 4-pregnen 11beta,16alpha-diol-3,20-dione catalysed by CYP11B2; the 5alpha-reduction of the latter and 16OHP4 catalysed by SRD5A yielding 5alpha-pregnan-11beta,16alpha-diol 3,20-diovne and 5alpha-pregnan-16alpha-ol-3,20-dione (16OH-DHP4); and 16OH-DHP4 converted by AKR1C2 to 5alpha-pregnan-3alpha,16alpha-diol-20-one. Receptor studies showed 16OHP4, 16OH-DHP4, progesterone and dihydroprogesterone (DHP4) were weak partial AR agonists; 16OHP4, 16OH-DHP4 and DHP4 exhibited weak partial agonist activity towards PR-B with DHP4 also exhibiting partial agonist activity towards PR-A. Data showed that while the 5alpha-reduction of P4 decreased PR activation significantly, 16OHP4 and 16OH-DHP4 exhibited comparable receptor activation. Although the clinical relevance of 16OHP4 remains unclear the elevated 16OHP4 levels characteristic of 21OHD, CAH, PCOS, prostate cancer, testicular feminization syndrome and cryptorchidism likely contribute towards these clinical conditions, inducing receptor-activated target genes. PMID- 27664518 TI - The role of AMH and its receptor SNP in the pathogenesis of PCOS. AB - The etiology of polycystic ovaries syndrome (PCOS) is unknown. Studies probing the role of genetic variants of anti-Mullerian hormone (AMH) and its type II receptor (AMHR2) in the pathogenesis of PCOS have yielded inconsistent results. Thus, we performed a systematic review and meta-analysis to determine the role of genetic variants of AMH/AMHR2 in the pathogenesis of PCOS. A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). Pooled Odds Ratios (OR) (95% confidence intervals) were determined to assess the association between genetic variants of AMH/AMHR2 and PCOS. Five studies, involving a total of 2042 PCOS cases and 1071 controls, were included in the meta-analysis. Single nucleotide polymorphisms of AMH and AMHR2 did not appear to confer a heightened risk for PCOS (OR: 0.954, 95% CI: 0.848-1.073; P = 0.435; and OR: 1.074, 95% CI: 0.875 1.318; P = 0.494, respectively). In this study, genetic variants of AMH or AMHR2 were not found to be associated with a higher risk for PCOS. PMID- 27664519 TI - NADPH oxidase-2 does not contribute to beta-cell glucotoxicity in cultured pancreatic islets from C57BL/6J mice. AB - High glucose-induced oxidative stress and increased NADPH oxidase-2 (NOX2) activity may contribute to the progressive decline of the functional beta-cell mass in type 2 diabetes. To test that hypothesis, we characterized, in islets from male NOX2 knockout (NOX2-KO) and wild-type (WT) C57BL/6J mice cultured for up to 3 weeks at 10 or 30 mmol/l glucose (G10 or G30), the in vitro effects of glucose on cytosolic oxidative stress using probes sensing glutathione oxidation (GRX1-roGFP2), thiol oxidation (roGFP1) or H2O2 (roGFP2-Orp1), on beta-cell stimulus-secretion coupling events and on beta-cell apoptosis. After 1-2 days of culture in G10, the glucose stimulation of insulin secretion (GSIS) was ~1.7-fold higher in NOX2-KO vs. WT islets at 20-30 mmol/l glucose despite similar rises in NAD(P)H and intracellular calcium concentration ([Ca2+]i) and no differences in cytosolic GRX1-roGFP2 oxidation. After long-term culture at G10, roGFP1 and roGFP2-Orp1 oxidation and beta-cell apoptosis remained low, and the glucose induced rises in NAD(P)H, [Ca2+]i and GSIS were similarly preserved in both islet types. After prolonged culture at G30, roGFP1 and roGFP2-Orp1 oxidation increased in parallel with beta-cell apoptosis, the glucose sensitivity of the NADPH, [Ca2+]i and insulin secretion responses increased, the maximal [Ca2+]i response decreased, but maximal GSIS was preserved. These responses were almost identical in both islet types. In conclusion, NOX2 is a negative regulator of maximal GSIS in C57BL/6J mouse islets, but it does not detectably contribute to the in vitro glucotoxic induction of cytosolic oxidative stress and alterations of beta-cell survival and function. PMID- 27664520 TI - Degradation of ciprofloxacin by 280 nm ultraviolet-activated persulfate: Degradation pathway and intermediate impact on proteome of Escherichia coli. AB - In this study, the degradation of ciprofloxacin (CIP) was explored using ultraviolet activated persulfate (UV/PS) with 280 nm ultraviolet light-emitting diodes (UV-LEDs), and the toxicological assessment of degrading intermediates was performed using iTRAQ labeling quantitative proteomic technology. The quantitative mass spectrum results showed that 280 nm UV/PS treatment had a high transformation efficiency of CIP ([CIP] = 3 MUM, [S2O82-] = 210 MUM, apparent rate constants 0.2413 min-1). The high resolution mass spectrum analyses demonstrated that the primary intermediates included C15H16FN3O3 (m/z 306.1248) and C17H18FN3O4 (m/z 348.1354). The former one was formed by the cleavage of piperazine ring, while the later one was generated by the addition of a hydroxyl on the quinolone backbone. The toxicological assessment demonstrated that 56 and 110 proteins had significant up regulations and down regulations, respectively, in the Escherichia coli exposed to degraded CIP compared to untreated CIP. The majority of up-regulated proteins, such as GapA, SodC, were associated with primary metabolic process rather than responses to stress and toxic substance, inferring that the moderate UV/PS treatment can reduce the antibacterial activity of CIP by incomplete mineralization. Consequently, these results provided a novel insight into the application of UV-LED/PS treatment as a promising removal methodology for quinolones. PMID- 27664521 TI - Weather dependent dynamics of the herbicides florasulam, carfentrazone-ethyl, fluroxypyr-meptyl and fluroxypyr in wheat fields through field studies and computational simulation. AB - A dynamic model of dynamiCROP was applied to study environmental fate and behavior of four herbicides in wheat including florasulam, carfentrazone-ethyl, fluroxypyr-meptyl, and fluroxypyr. Meantime, their residue in wheat and dissipation half-lives in plant determined by field trials using QuEChERS liquid chromatography tandem mass spectrometry were used to verify modelling results. The combination of experimental verification and modelling prediction deciphered the fate of four pesticides in wheat field ecosystem. Besides, temperature difference of 3 degrees C only resulted in lower than 15% half-life difference. By quantifying the contribution of temperature, the predominant role of rain on pesticide dissipation was highlighted for the first time, namely higher precipitation leaded to faster degradation and vice versa. PMID- 27664522 TI - Characteristics of water and ion exchange of Elodea nuttallii cells at high concentrations of lanthanides. AB - Changes of diffusive permeability of membranes of Elodea nuttallii cells following a short-term (60 min) treatment with high concentrations of lanthanides were recorded by the 1H NMR-diffusometry and conductometry methods. The 1-h infiltration of segments of Elodea nuttallii internodes in 10 mM solutions of nitrates of La, Nd and Lu resulted in the increased leakage of electrolytes from cells, but has no effect on a water diffusive permeability of membranes. In samples subjected to a 30 min pretreatment with a water channel inhibitor HgCl2 the water diffusive permeability of membranes (Pd) drops down under the influence of lanthanides, as well as an outcome of electrolytes. To explain the observed effects the change of spontaneous curvature of membrane lipid layer has been taken into consideration. The interaction of lanthanides with lipids of plasmalemma leads to the negative spontaneous curvature of lipid layer at which membrane channels are unclosed. Blocking of the ionic and water channels by mercury ions compensate the effect of change of spontaneous curvature of lipid layer. PMID- 27664523 TI - Post-deposition early-phase migration and retention behavior of radiocesium in a litter-mineral soil system in a Japanese deciduous forest affected by the Fukushima nuclear accident. AB - The fate of radiocesium (137Cs) derived from the Fukushima nuclear accident and associated radiation risks are largely dependent on its migration and retention behavior in the litter-soil system of Japanese forest ecosystems. However, this behavior has not been well quantified. We established field lysimeters in a Japanese deciduous broad-leaved forest soon after the Fukushima nuclear accident to continuously monitor the downward transfer of 137Cs at three depths: the litter-mineral soil boundary and depths of 5 cm and 10 cm in the mineral soil. Observations were conducted at two sites within the forest from May 2011 to May 2015. Results revealed similar temporal and depth-wise variations in 137Cs downward fluxes for both sites. The 137Cs downward fluxes generally decreased year by year at all depths, indicating that 137Cs was rapidly leached from the forest-floor litter layer and was then immobilized in the upper (0-5 cm) mineral soil layer through its interaction with clay minerals. The 137Cs fluxes also showed seasonal variation, which was in accordance with variations in the throughfall and soil temperature at the sites. There was no detectable 137Cs flux at a depth of 10 cm in the mineral soil in the third and fourth years after the accident. The decreased inventory of mobile (or bioavailable) 137Cs observed during early stages after deposition indicates that the litter-soil system in the Japanese deciduous forest provides only a temporary source for 137Cs recycling in plants. PMID- 27664524 TI - Assessment of the mutagenic, recombinogenic and carcinogenic potential of fipronil insecticide in somatic cells of Drosophila melanogaster. AB - Fipronil (FP) is an insecticide that belongs to the phenylpyrazole chemical family and is used to control pests by blocking GABA receptor at the entrance channel of the chlorine neurons. The aim of this study was to evaluate the mutagenic, recombinogenic and carcinogenic potential of FP. The mutagenic and recombinogenic effects were evaluated using the somatic mutation and recombination test (SMART) on wing cells of Drosophila melanogaster. Third instar larvae from standard (ST) and high bioactivation (HB) crosses were treated with different concentrations of FP (0.3, 0.7, 1.5 or 3.0 * 10-5 mM). The results showed mutagenic effects at all concentrations tested in the HB cross; and all concentrations tested in the ST cross, except at concentration of 0.7 * 10-5 mM. The carcinogenic effect of FP was assayed through the test for detection of epithelial tumor (warts) in D. melanogaster. Third instar larvae from wts/TM3 virgin females mated to mwh/mwh males were treated with different concentrations of FP (0.3, 0.7, 1.5 or 3.0 * 10-5 mM). All these concentrations induced a statistically significant increase in tumor frequency. In conclusion, FP proved to be mutagenic, recombinogenic and carcinogenic in somatic cells of D. melanogaster. PMID- 27664525 TI - One-pot hydrothermal synthesis of Zinc ferrite/reduced graphene oxide as an efficient electrocatalyst for oxygen reduction reaction. AB - Fabrication of low-cost and efficient electrocatalyst for oxygen reduction reaction (ORR) is highly desirable. Herein, Zinc ferrite/reduced graphene oxide (ZnFe2O4/rGO) is prepared by a quite simple and environmentally benign approach and applied as a high performance ORR electrocatalyst for the first time. The surface morphology and chemical composition of ZnFe2O4/rGO are characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetric analysis and Fourier transform infrared spectroscopy. Cyclic voltammetry, linear sweep voltammetry and chronoamperometry are used to evaluate the electrochemical activities and stabilities of ZnFe2O4/rGO catalysts in alkaline media. Among ZnFe2O4/rGO with different mass ratios, the catalyst with 69.8wt% ZnFe2O4 (called ZnFe2O4/rGO (3)) has the best catalytic activities and it shows much superior methanol tolerance and better durability than the commercial Pt/C catalyst. Due to the synergistic effect, the ZnFe2O4/rGO (3) nanohybrid exhibits high ORR catalytic performance and durability, which follows a desirable four electron transfer mechanism in alkaline media. Therefore, it may be a highly competitive catalyst for fuel cells and metal-air batteries. PMID- 27664526 TI - Thermo-responsive triblock copolymer phase transition behaviour in imidazolium based ionic liquids: Role of the effect of alkyl chain length of cations. AB - Different biophysical techniques such as fluorescence spectroscopy, dynamic light scattering (DLS), viscosity (eta) and Fourier transform infrared (FTIR) spectroscopy have been carried out to characterize the effect of imidazolium based ionic liquids (ILs) on the thermo-responsive triblock copolymer, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly-(ethylene glycol) (PEG-PPG-PEG). In addition, to demonstrate the distinct morphological changes of various self-assembled morphologies, we further employed field emission scanning electron microscope (FESEM). To investigate the effect of alkyl chain length of the cation, concentration of the ILs and the related Hofmeister series on the phase behaviour of PEG-PPG-PEG, we used a series of ILs possessing same Cl- anion and a set of cation [Cnmim]+ with increasing alkyl chain length of cation such as 1-ethyl-3-methylimidazolium chloride ([Emim][Cl]), 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]), 1-hexyl-3-methylimidazolium chloride ([Hmim][Cl]) and 1 decyl-3-methylimidazolium chloride ([Dmim][Cl]). The critical micellization temperature (CMT) of the copolymer in the presence of well hydrated cations is directly correlated to their hydration. The overall specific ranking of ILs in decreasing the CMT of PEG-PPG-PEG in aqueous solution was [Emim][Cl]>[Bmim][Cl]>[Hmim][Cl]>[Dmim][Cl]. The trend of these ILs followed the well-known Hofmeister series of cations of ILs. The present study provides important information about the solution properties that can be helpful to tune the IL or temperature-sensitive copolymer CMT and micelle shapes which are crucial for understanding the drug delivery mechanisms. PMID- 27664527 TI - Enhanced adsorption of the cationic dyes in the spherical CuO/meso-silica nano composite and impact of solution chemistry. AB - In this study, the spherical mesoporous silica (meso-silica MCM-41) and that inorganically modified with CuO (CuO/MCM-41 nano composite) were synthesized and characterized. It was demonstrated that CuO were successfully loaded in the synthesized nano composite CuO/MCM-41. Importantly, the loaded CuO had a significant enhancement effect on the adsorption of Crystal violet and Methylene blue. Adsorption kinetic of the tested cationic dyes in the synthesized materials fitted the pseudo-second-order kinetic model and Weber's intra-particle diffusion model well. According to the Langmuir isotherm model, the maximum adsorption capacities (Qmax) of the CuO/MCM-41 towards Crystal violet and Methylene blue increased to 52.9 and 87.8mg/g, while those of the pure MCM-41 were 46.2 and 65.7mg/g, respectively. Due to the surface charge of CuO and the protonation of the dye molecules, the electrostatic forces between the loaded CuO and the organic cationic dyes contributed to the enhancement effect. Additionally, the presented results indicated that the adsorption of the cationic dyes in the CuO/MCM-41 depended on pH and ion strength of the solution but insignificantly on the coexisted humic acid due to the mesoporous character of CuO/MCM-41 nano composite. PMID- 27664528 TI - Phosphate uptake studies of cross-linked chitosan bead materials. AB - A systematic experimental study is reported that provides a molecular based understanding of cross-linked chitosan beads and their adsorption properties in aqueous solution containing phosphate dianion (HPO42-) species. Synthetically modified chitosan using epichlorohydrin and glutaraldehyde cross-linkers result in surface modified beads with variable hydrophile-lipophile character and tunable HPO42- uptake properties. The kinetic and thermodynamic adsorption properties of cross-linked chitosan beads with HPO42- species were studied in aqueous solution. Complementary structure and physicochemical characterization of chitosan beads via potentiometry, Raman spectroscopy, DSC, and dye adsorption measurements was carried out to establish structure-property relationships. The maximum uptake (Qm) of bead systems with HPO42- at equilibrium was 52.1mgg-1; whereas, kinetic uptake results for chitosan bead/phosphate systems are relatively rapid (0.111-0.113min-1) with an intraparticle diffusion rate-limiting step. The adsorption process follows a multi-step pathway involving inner- and outer-sphere complexes with significant changes in hydration. Phosphate uptake strongly depends on the composition and type of cross-linker used for preparation of chitosan beads. The adsorption isotherms and structural characterization of bead systems illustrate the role of surface charge, hydrophile-lipophile balance, adsorption site accessibility, and hydration properties of the chitosan bead surface. PMID- 27664529 TI - Smart magnetic ionic liquid-based Pickering emulsions stabilized by amphiphilic Fe3O4 nanoparticles: Highly efficient extraction systems for water purification. AB - This study presents the general method to formulate magnetically responsive ionic liquid (IL)-based Pickering emulsions that are stabilized by amphiphilic Fe3O4 nanoparticles. The magnetic nanoparticle stabilizer (MN-CHOL) was synthesized using the surface-initiated ATRP method with further modification that uses a specially designed cholesteryl derivative, and characterized by FT-IR, XPS, TGA, and magnetization measurements. It is confirmed that the resulting MN-CHOL shows a stronger interfacial activity, efficiently emulsifying C4mim [PF6] and water, and resultantly forming stable Pickering emulsions without the help of any co surfactant. Due to its super paramagnetism and high saturation magnetization, MN CHOL attached on the IL interface enables droplets of IL to be moved very conveniently on their target for as many times by an external magnetic field without demulsification, indicating high controllability and excellent stability. The resulting Pickering emulsion is a good extraction system that efficiently separates chlorobenzene, phenol, and methyl orange from aqueous solution. Subsequently, the simple magnetic separation was applied, to produce purified water due as a result of the rapid removal of organic pollutants from contaminated water. PMID- 27664530 TI - Emotional and behavioral difficulties in children growing up homeless in Paris. Results of the ENFAMS survey. AB - PURPOSE: Children growing up in homeless families are disproportionately more likely to experience health and psychological problems. Our objective was to describe social, environmental, individual and family characteristics associated with emotional and behavioral difficulties among homeless children living in the Paris region. METHODS: Face-to-face interviews with a representative sample of homeless families were conducted by bilingual psychologists and interviewers between January and May 2013 (n=343 children ages 4-13 years). Mothers reported children's emotional and behavioral difficulties (Strength and Difficulties Questionnaire [SDQ]), family socio-demographic characteristics, residential mobility, and parents' and children's physical and mental health. Children were interviewed regarding their perception of their living arrangements, friendships and school experiences. We studied children's SDQ total score in a linear regression framework. RESULTS: Homeless children had higher SDQ total scores than children in the general population of France, (mean total score=11.3 vs 8.9, P<0,001). In multivariate analyses, children's difficulties were associated with parents' region of birth (beta=1.74 for Sub-Saharan Africa, beta=0.60 for Eastern Europe, beta=3.22 for other countries, P=0.020), residential mobility (beta=0.22, P=0.012), children's health (beta=3.49, P<0.001) and overweight (beta=2.14, P=0.007), the child's sleeping habits (beta=2.82, P=0.002), the mother's suicide risk (beta=4.13, P<0.001), the child's dislike of the family's accommodation (beta=3.59, P<0.001) and the child's experience of bullying (beta=3.21, P=0.002). CONCLUSIONS: Children growing up homeless experience high levels of psychological difficulties which can put them at risk for poor mental health and educational outcomes long-term. Access to appropriate screening and medical care for this vulnerable yet underserved group are greatly needed. PMID- 27664531 TI - Brief self-compassion meditation training for body image distress in young adult women. AB - Self-compassion interventions may be uniquely suited to address body image distress (BID), as change-based strategies may have limited utility in a cultural context that so highly values appearance. The current study evaluated a version of an Internet-based self-compassion training, which had previously shown promising results, but was limited by high attrition. The intervention period was reduced from three weeks to one week in the present study to improve retention. Eighty undergraduate women endorsing body image concerns were randomized to either self-compassion meditation training or a waitlist control group. Results suggest that brief exposure to the basic tenets of self-compassion holds promise for improving aspects of self-compassion and BID. Attrition was minimal, but compliance with meditation practice instructions during the week was low. Efforts are needed to improve engagement, but this approach has the potential to be an acceptable and cost effective method to reduce BID. PMID- 27664532 TI - Altered exposure-related reshaping of body appreciation in adolescent patients with anorexia nervosa. AB - Several studies suggest a relation between repeated exposure to extremely thin bodies in media and the perceptual and emotional disturbances of body representation in anorexia nervosa (AN). In this study, we utilized an exposure paradigm to investigate how perceptual experience modulates body appreciation in adolescents with AN as compared to healthy adolescents. Twenty AN patients and 20 healthy controls were exposed to pictures of thin or round models and were then required to express liking judgments about bodies of variable weight. Brief exposure to round models increased the liking judgments of round bodies but not those of thin bodies in healthy adolescents. Furthermore, exposure to round models increased the liking judgments of both thin and round bodies in adolescents with AN. Patients did not show any change of liking judgments after exposure to thin models. These results point to weak norm-based reshaping of body appreciation in AN patients. PMID- 27664533 TI - Responses to Crizotinib Can Occur in High-Level MET-Amplified Non-Small Cell Lung Cancer Independent of MET Exon 14 Alterations. AB - Activation of the MET proto-oncogene (MET) highly sensitive to MET inhibition has recently been described in NSCLC through two mechanisms: high-level amplification of the MNNG HOS Transforming gene (MET) (usually expressed relative to the chromosome 7 centromere [CEP7] when using fluorescence in situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other or both can represent true oncogenic driver states continues to be explored. Cases of MET inhibitor-sensitive NSCLC harboring exon 14 alterations without coincident amplification have already been described. Here we report two cases of MET inhibitor-sensitive NSCLC harboring high-level MET amplification (MET/CEP7 ratio >=5) without coincident exon 14 alterations, suggesting that these two methods of MET activation can produce independent MET addicted states in NSCLC. Molecular profiling designed to capture all cases of potentially MET-addicted NSCLC should address both activation mechanisms. PMID- 27664534 TI - A Harmonization Study for the Use of 22C3 PD-L1 Immunohistochemical Staining on Ventana's Platform. AB - INTRODUCTION: Immunotherapy is a novel treatment for lung cancer. Pembrolizumab (Merck Sharp and Dohme, Kenilworth, NJ) is a monoclonal antibody against programmed cell death 1 that has been approved for use with NSCLC together with a companion diagnostic by Dako (Carpinteria, CA). Ventana's BenchMark XT (Ventana Medical Systems, Tucson, AZ) is a widely used immunohistochemical (IHC) platform. However, data on its reliability and reproducibility with the 22C3 antibody are scant. METHODS: We performed a comprehensive calibration of 22C3 programmed cell death ligand 1 (PD-L1) staining on the BenchMark XT platform using Dako's prediluted 22C3 anti-PD-L1 primary antibody with two of Ventana's detection systems. Forty-one random cases of NSCLC were then independently evaluated by two pathologists. Each case was scored using Dako- or Ventana-stained slides. The scores obtained with the two 22C3 Ventana assays were compared with those obtained using the Dako 22C3 IHC platform. RESULTS: The Dako IHC platform stratified eight, seven, and 26 cases as being strongly positive, weakly positive, and negative for PD-L1, respectively, whereas 36 of 41 cases (87.8%) had the same results with Ventana's UltraView 22C3 protocol (Pearson's correlation score 0.91, p < 0.0001). Moreover, 35 of 41 cases (85.3%) had the same results with Ventana's OptiView 22C3 protocol (Pearson's correlation score 0.89, p < 0.0001). CONCLUSIONS: The results of this study demonstrate that the same PD-L1 IHC algorithm can be reliably applied to Ventana's BenchMark XT platform. Furthermore, we were able to detect all of the strongly positive cases with high interobserver and intraobserver agreement by using the Ventana platform. These findings suggest that the Ventana platform can be used to stratify patients for pembrolizumab-based immunotherapy. PMID- 27664535 TI - Treatment of multiple myeloma with monoclonal antibodies and the dilemma of false positive M-spikes in peripheral blood. AB - OBJECTIVES: To characterize the effect of three humanized IgG kappa monoclonal antibodies (daratumumab, isatuximab, and elotuzumab) on the interpretation of results generated by protein electrophoresis, immunofixation, free light chain, and heavy/light chain assays performed on human serum. METHODS: Healthy volunteer serum and serum from multiple myeloma patients were supplemented with clinically relevant concentrations of each of the three monoclonal antibodies. These specimens then underwent analysis via serum protein electrophoresis, immunofixation, serum free light chain quantification, heavy/light chain quantification, total IgG, and total protein. In addition, serum specimens from patients who had undergone treatment with elotuzumab for multiple myeloma underwent similar analysis. RESULTS: Addition of the study drugs to serum from both the healthy donor as well as multiple myeloma patients resulted in a visible and quantifiable M-protein on SPEP and a visible IgGkappa band by IFE. Increases were also noted in total IgG, IgGkappa, and IgGkappa/IgGlambda-ratios. Analysis of serum from multiple myeloma patients receiving study drug showed similar findings with an additional IgGkappa band and quantifiable M-protein with similar migration patterns in specimens drawn after administration. CONCLUSION: The treatment of multiple myeloma patients with monoclonal antibodies results in a visible and quantifiable M-protein that has the potential to falsely indicate poor response to therapy. PMID- 27664536 TI - DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects. AB - Sertoli-Leydig cell tumors (SLCTs) are representative of androgenic ovarian tumors, and they show diverse histologic differentiation, including heterologous differentiation. Genetically, SLCTs are characterized by the presence of DICER1 mutations. In the present study, we analyzed the correlation between somatic DICER1 hotspot mutations and clinicopathological features in 10 ovarian SLCTs. Six of the 10 (60%) SLCTs harbored a DICER1 hotspot mutation. Five of the 6 DICER1-mutated SLCT patients showed androgenic manifestations, including amenorrhea and hirsutism, and 4 of the 6 were associated with the significant elevation of serum testosterone. In contrast, none of the 4 DICER1 wild-type SLCT patients showed virilization. The patient age at diagnosis was lower in those with DICER1-mutated SLCTs (average, 24.7; range, 17-43) than in those with DICER1 wild-type tumors (average, 64.8; range, 47-77). Histologically, heterologous differentiation was found in 4 SLCTs, all of which were DICER1 mutant. Heterologous components included gastrointestinal-type mucinous epithelium (n=3), carcinoid (n=1), and rhabdomyosarcoma (n=1). In the latter, the rhabdomyosarcomatous component was dominant to the SLCT component. In summary, DICER1 hotspot mutations are closely associated with androgenic effects in ovarian SLCTs. It is suggested that DICER1 mutations are involved in the dysregulation of sex hormone synthesis in SLCT patients. Somatic DICER1 hotspot mutations are more common in SLCT patients during the reproductive years than in those during the postreproductive years. DICER1 hotspot mutations may support the pathological diagnosis of SLCTs in cases wherein the heterologous component overwhelms and masks the SLCT component. PMID- 27664538 TI - Residential proximity to urban centres, local-area walkability and change in waist circumference among Australian adults. AB - Consistent associations have been observed between macro-level urban sprawl and overweight/obesity, but whether residential proximity to urban centres predicts adiposity change over time has not been established. Further, studies of local area walkability and overweight/obesity have generated mixed results. This study examined 4-year change in adults' waist circumference in relation to proximity to city centre, proximity to closest suburban centre, and local-area walkability. Data were from adult participants (n=2080) of a cohort study on chronic conditions and health risk factors in Adelaide, Australia. Baseline data were collected in 2000-03 with a follow-up in 2005-06. Multilevel regression models examined in 2015 the independent and joint associations of the three environmental measures with change in waist circumference, accounting for socio demographic covariates. On average, waist circumference rose by 1.8cm over approximately 4years. Greater distance to city centre was associated with a greater increase in waist circumference. Participants living in distal areas (20km or further from city centre) had a greater increase in waist circumference (mean increase: 2.4cm) compared to those in proximal areas (9km or less, mean increase: 1.2cm). Counterintuitively, living in the vicinity of a suburban centre was associated with a greater increase in adiposity. Local-area walkability was not significantly associated with the outcome. Residential proximity to city centre appears to be protective against excessive increases in waist circumference. Controlled development and targeted interventions in the urban fringe may be needed to tackle obesity. Additional research needs to assess behaviours that mediate relationships between sprawl and obesity. PMID- 27664539 TI - News media coverage of U.S. Ebola policies: Implications for communication during future infectious disease threats. AB - The Ebola outbreak of 2014-2015 raised concerns about the disease's potential spread in the U.S. and received significant news media coverage. Prior research has shown that news media coverage of policy options can influence public opinion regarding those policies, as well as public attitudes toward the broader social issues and target populations addressed by such policies. To assess news media coverage of Ebola policies, the content of U.S.-focused news stories (n=1262) published between July 1 and November 30, 2014 from 12 news sources was analyzed for 13 policy-related messages. Eight-two percent of news stories mentioned one or more policy-related messages. The most frequently appearing policy-related messages overall were those about isolation (47%) and quarantine (40%). The least frequently mentioned policy-related message described dividing potentially exposed persons into distinct groups based on their level of Ebola risk in order to set different levels of restrictions (5%). Message frequency differed depending on whether news sources were located in an area that experienced an Ebola case or controversy, by news sources' political ideological perspective, and by type of news source (print and television). All policy-related messages showed significant increases in frequency after the first case of Ebola was diagnosed in the U.S. on September 30, 2014, with the exception of messages related to isolation, which showed a significant decrease. Results offer insight into how the news media covers policies to manage emerging disease threats. PMID- 27664540 TI - Molecular cloning and characterization of unfolded protein response genes from large yellow croaker (Larimichthys crocea) and their expression in response to dietary fatty acids. AB - The unfolded protein response (UPR) is a mechanism to cope with perturbed endoplasmic reticulum (ER) functions or accumulation of unfolded protein in the ER in eukaryotic cells. Furthermore, the UPR also participates in a number of physiological and pathological processes, such as nutrient sensing, lipid synthesis, and inflammatory response. In this study, four UPR-related genes (GRP78/BiP, ATF6alpha, XBP1 and CHO) were isolated characterized from large yellow croaker (Larimichthys crocea), and their expression in response to dietary lipid sources (various fatty acids) such as fish oil (FO), palmic acid (PA), olive oil (OO), sunflower oil (SO), and perilla oil (PO), were examined following feeding. The results showed that the four UPR-related proteins contained highly conserved functional domains and had the closest phylogenetic relationships with other fishes. Additionally, these genes were ubiquitously expressed in large yellow croaker, as in zebrafish and medaka. Moreover, GRP78, ATF6alpha and spliced XBP1 (XBP1s) mRNA levels in the liver, not in adipose tissue, were significantly increased in the SO group compared to the other groups (P<0.05). These results indicated that dietary SO activated UPR, and the activation of UPR might provide a mechanism to improve ER function, but probably stimulated lipid synthesis and caused inflammatory response in the liver of large yellow croaker. PMID- 27664537 TI - Targeted next-generation sequencing of CIC-DUX4 soft tissue sarcomas demonstrates low mutational burden and recurrent chromosome 1p loss. AB - Gene fusions between CIC and DUX4 define a rare class of soft tissue sarcomas poorly understood at the molecular level. Previous karyotyping and fluorescence in situ hybridization studies support chromosome 8 trisomy as a recurrent alteration; however, other driving alterations are largely unknown. Thus, we analyzed 11 formalin-fixed, paraffin-embedded CIC-DUX4 sarcoma tissue samples (including 3 sample pairs) using targeted Ion Torrent-based multiplexed polymerase chain reaction next-generation sequencing to characterize potential somatic driver alterations in 409 genes. Although we did not identify recurrent somatic mutations (point mutations or insertions/deletions), copy number analysis showed recurrent, broad copy number alterations, including gain of chromosome 8 and loss of 1p. In one sample pair (untreated primary and local recurrence resections), we identified similar copy number profiles and a somatic ARID1A R963X nonsense mutation exclusively in the local recurrence sample. In another sample pair (pre- and post-radiation treatment specimens), we observed single copy loss of chromosome 7q exclusively in the posttreatment recurrence sample, supporting it as an acquired event after radiation treatment. In the last sample pair (near-concurrent, postchemotherapy primary and distant metastasis), molecular profiles were highly concordant, consistent with limited intertumoral heterogeneity. In summary, next-generation sequencing identified limited somatic driver mutations in CIC-DUX4 sarcomas. However, we identified novel, recurrent copy number alterations, including chromosome 1p, which is also the locus of ARID1A. Additional functional work and assessment of larger cohorts are needed to determine the biological and clinical significance of the alterations identified herein. PMID- 27664542 TI - Effect of chloride on the formation of volatile disinfection byproducts in chlorinated swimming pools. AB - Chloride can accumulate in chlorinated swimming pool water. Although substantial efforts have been made to examine the effects of halide ions on the formation of volatile disinfection byproducts (DBPs), most have focused on bromide. The effects of chloride ion concentration on the formation of volatile DBPs in swimming pools remain largely unstudied. In this study, chlorination of typical precursors and body fluid analogue (BFA) were investigated with variable chloride concentration and pH. The formation of three volatile DBPs (NCl3, CHCl3 and CNCHCl2) was observed to be linearly correlated with chloride concentration, both in bench experiments and in actual swimming pool water samples. Free chlorine consumption was also observed to increase with chloride concentration. These behaviors appear to be attributable to shifts in speciation of free chlorine, with higher chloride resulting in higher concentration of molecular chlorine (Cl2), which is much more reactive than HOCl. The results of this work suggest that changes in pool management strategies to promote low chloride concentration could be important for control of volatile DBPs in pools and to economize free chlorine usage. PMID- 27664541 TI - Mechanically enhanced PES electrospun nanofiber membranes (ENMs) for microfiltration: The effects of ENM properties on membrane performance. AB - The application of electrospun nanofiber membranes (ENMs) as microfilters for the process of water purification requires the substrate to possess suitable strength, permeability, and a smooth surface. Therefore, the fiber homogeneity, inter-fiber adhesion, and surface roughness of the ENMs must be carefully controlled. Concurrently, an understanding of the ENMs' rejection mechanism for contaminants is necessary for the effective application of ENMs. In this study, we demonstrate the fabrication of polyethersulfone (PES) ENMs, which are useful for water purification as water treatment membranes. An optimum fabrication condition that can significantly improve the mechanical property and surface roughness of the PES membrane is also illustrated. This technique induces the solvent remaining on the fiber's surface after the electrospinning process, and the mechanical properties and surface roughness of the membrane are improved by the solvent-induced fusion of the fiber. The fabricated PES ENMs also show higher clean water productivity. Additionally, we show that a particulate contaminant in water is mainly rejected on the ENM surface by using a water filtration test. Based on our conclusions, we suggest the appropriate ENM regeneration method and confirm that the fabricated ENMs show excellent regeneration ability. PMID- 27664544 TI - The weak fundamental NH-stretching transition in amines. AB - Absolute intensities of NH-stretching fundamental and overtone transitions of gas phase aniline, methylamine, ethylamine, cyclopropylamine, methylethylamine, diethylamine and pyrrolidine have been measured with long path length conventional absorption spectroscopy. To support the assignments of NH-stretching transitions, transition frequencies and intensities were calculated with the local mode model using ab initio calculated local mode parameters and dipole moment functions obtained at the CCSD(T)-F12a/VDZ-F12 level of theory. For aniline, the absolute intensities of the NH-stretching transitions show the typical decrease of approximately an order of magnitude for each successive vibrational excitation. For methylamine, ethylamine, cyclopropylamine, methylethylamine, diethylamine and pyrrolidine, the observed absolute intensities of the fundamental NH-stretching transition is weak and of similar strength or even weaker than the corresponding first overtone transition. Characteristic for the amines with a normal fundamental intensity is a conjugated double bond next to the amine group. PMID- 27664543 TI - Beyond feast and famine: Selecting a PHA accumulating photosynthetic mixed culture in a permanent feast regime. AB - Currently, the feast and famine (FF) regime is the most widely applied strategy to select for polyhydroxyalkanoate (PHA) accumulating organisms in PHA production systems with mixed microbial cultures. As an alternative to the FF regime, this work studied the possibility of utilizing a permanent feast regime as a new operational strategy to select for PHA accumulating photosynthetic mixed cultures (PMCs). The PMC was selected in an illuminated environment and acetate was constantly present in the mixed liquor to guarantee a feast regime. During steady state operation, the culture presented low PHA accumulation levels, likely due to low light availability, which resulted in most of the acetate being used for biomass growth (Yx/s of 0.64 +/- 0.18 Cmol X/Cmol Acet). To confirm the light limitation on the PMC, SBR tests were conducted with higher light availability, at similar levels as would be expectable from natural sunlight. In this case, the Yx/s reduced to 0.11 +/- 0.01 Cmol X/Cmol Acet and the culture presented a PHB production yield on acetate of 0.67 +/- 0.01 Cmol PHB/Cmol Acet, leading to a maximum PHB content of 60%. Unlike other studied PMCs, the PMC was capable of simultaneous growth and PHB accumulation continuously throughout the cycle. Thus far, 60% PHA content is the maximum value ever reported for a PMC, a result that prospects the utilization of feast regimes as an alternative strategy for the selection of PHA accumulating PMCs. Furthermore, the PMC also presented high phosphate removal rates, delivering an effluent that complies with phosphate discharge limits. The advantages of selecting PMCs under a permanent feast regime are that no aeration inputs are required; it allows higher PHA contents and phosphate removal rates in comparison to FF-operated PMC systems; and it represents a novel means of integrating wastewater treatment with resource recovery in the form of PHA. PMID- 27664545 TI - Colorimetric detection of glucose based on gold nanoparticles coupled with silver nanoparticles. AB - We have coupled gold nanoparticles (AuNPs) with silver nanoparticles (AgNPs) to assemble a plasmonic sensing platform for colorimetric detection of glucose. In this system, small AuNPs (~4nm) can act as glucose oxidase (GOD) mimic enzyme to catalytically oxidize glucose in the presence of oxygen, producing hydrogen peroxide, which dissolves AgNPs to lead the color changes. Glucose can be detected not only by naked eyes (from yellow to red) but also by spectrophotometer in the concentration range of 5-70MUM, with detection limit of 3MUM. More importantly, we found that l-cysteine added in the system can markedly improve the selectivity for the detection of glucose. The proposed method was used to application for the detection of glucose in human serum with satisfactory results. This system is simple and low cost without using any enzymes and organic chromogenic agents. PMID- 27664546 TI - Raising awareness of the importance of funding for tuberculosis small-molecule research. AB - Tuberculosis (TB) drug discovery research is hampered by several factors, but as in many research areas, the available funding is insufficient to support the needs of research and development. Recent years have seen various large collaborative efforts involving public-private partnerships, mimicking the situation during the golden age of antibiotic drug discovery during the 1950s and 1960s. The large-scale collaborative efforts funded by the European Union (EU) are now subject to diminishing financial support. As a result, TB researchers are increasingly looking for novel forms of funding, such as crowdfunding, to fill this gap. Any potential solution will require a careful reassessment of the incentives to encourage additional organizations to provide funding. PMID- 27664547 TI - Shame, trauma, temperament and psychopathology: Construct validity of the Experience of Shame Scale. AB - Although Experience of Shame Scale (ESS) is used in clinical research and it covers psychiatrically relevant dimensions of chronic shame, characterological (CS), behavioral (BS) and bodily (BoS) respectively, its factor structures were not confirmed on clinical sample. The goals of our research were to examine the factor structure of the Hungarian version of ESS, in addition, to analyze the associations between factors of ESS and different types of predictors, such as clinical status, gender, age, school years, early abuse history, general psychopathology (GSI), and temperament dimensions by using a series of confirmatory factor analyses (CFA) with covariates in a large clinical and matched healthy sample. Psychiatric inpatients (N=148) and healthy control subjects (N=148) participated in this cross-sectional questionnaire study. In both samples, the degree of fit was adequate. The final CFA with covariates model showed significant and positive associations between CS and clinical status and education respectively, between CS, BS, BoS and frequency of verbal abuse, between CS and BoS and GSI and between CS and BS and harm avoidance and in addition we found negative associations between each of the shame factors and age. Our results support the psychiatric validity of the ESS construct. PMID- 27664548 TI - Impact of cognitive-behavioral group therapy for obsessive-compulsive disorder on family accommodation: A randomized clinical trial. AB - The aim of this study was to assess the impact of cognitive-behavioral group therapy (CBGT) with the brief involvement of family members on family accommodation and to identify predictors of family accommodation reduction (patient and family member characteristics). This randomized clinical trial assessed 98 pairs of patients with obsessive-compulsive disorder (OCD) and their family members: 52 (53.1%) were allocated to the intervention group (12 CBGT sessions - two with the family member), and 46 (46.9%) to a waiting list (control group). Symptom severity and family accommodation were assessed before and after CBGT. There was significant improvement of OCD symptoms and family accommodation scores after CBGT in the intervention group vs. the control group. The following variables were significant predictors of family accommodation reduction after multivariate analysis: patient characteristics - absence of comorbid unipolar disorder, lower obsession score, and higher education level; family member characteristics - higher hoarding score. The model explained 47.2% of the variance in family accommodation scores after treatment. CBGT for patients with OCD and the brief involvement of family members contributed to reduce family accommodation. Both patient and family member characteristics were predictors of family accommodation reduction. This finding can help qualify CBGT protocols. PMID- 27664549 TI - Assessment of attachment in psychosis: A psychometric cause for concern. AB - Attachment has recently been proposed as a key developmental construct in psychosis, in particular with respect to interpersonal functioning and social cognition. The current study examined the latent structure of the self-report Psychosis Attachment Measure (PAM) and its relationship to lower-level perceptual and higher-order inferential social cognitive processes. The PAM was administered to 138 psychiatrically stable outpatients with schizophrenia alongside a battery of symptom, social cognitive, and functional measures. PAM responses were analyzed using latent variable measurement models, which did not yield evidence of the coherent two-dimensional structure predicted by previous literature. A unidimensional subscale comprising 6 of the 16 original PAM items possessed the strongest psychometric properties. This subscale was generally uncorrelated with social cognitive measures and showed weak correlations with some symptoms measures and with community functioning. These results suggest that either the PAM may not measure attachment in psychosis or it may measure only attachment anxiety but demonstrate little construct validity in this population. These results tell a cautionary tale regarding making theoretical inferences on the basis of measures without coherent latent structure. Attachment measures with stronger psychometric properties will help clarify putative relationships between attachment and social cognitive processes in psychosis. PMID- 27664551 TI - Longitudinal changes in psychological distress in a cohort of people who inject drugs in Melbourne, Australia. AB - BACKGROUND: Previous research into psychological distress among people who inject drugs (PWID) is predominantly cross-sectional; we determined longitudinal predictors of change in psychological distress among a cohort of PWID. METHOD: We examined Kessler Psychological Distress Scale (K10) scores from 564 PWID (66% male) enrolled in the Melbourne Injecting Drug User Cohort Study. Gender stratified linear models with fixed effects for each participant were used to examine correlates of change in individual K10 scores. Further linear regressions of adjusted K10 scores were used to measure correlations between demographic variables. RESULTS: Participants reported higher K10 scores (higher psychological distress) than the general Australian population (mean K10 scores 23.4 (95%CI 22.6-24.2) and 14.5 (95%CI 14.3-14.7) respectively). The cohort's mean K10 score did not significantly differ over time, but individual variations were common. Women reported higher K10 scores than men (mean baseline K10 scores 25.2 (95%CI 23.9-26.6) and 22.4 (95%CI 21.5-23.3) respectively), however no significant differences remained after controlling for temporal factors. Key predictors of increases in K10 scores were being the victim of an assault in the past six months (P<0.001 for women and men) and intentionally overdosing in the past 12 months (P=.010 for women and P<0.001 for men). CONCLUSIONS: PWID experience higher levels of psychological distress than the general population. Temporal rather than individual factors may account for the higher levels of psychological distress reported among women. Interventions to reduce rates of assault and/or intentional overdose should be explored to reduce high levels of psychological distress among PWID. PMID- 27664550 TI - Central nervous system infection following allogeneic hematopoietic stem cell transplantation. AB - OBJECTIVE/BACKGROUND: Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. METHODS: Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. RESULTS: A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. CONCLUSION: Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). PMID- 27664552 TI - Cost-effectiveness of center-based compulsory rehabilitation compared to community-based voluntary methadone maintenance treatment in Hai Phong City, Vietnam. AB - INTRODUCTION: In Vietnam, two dominant approaches for heroin treatment are center based compulsory rehabilitation (CCT), funded by the Vietnamese government and community-based voluntary methadone maintenance treatment (MMT), funded primarily by international donors. Recent reduction in international funding requires more efficient allocation of government funding for public health programs. A cost effectiveness analysis comparing two approaches provides a useful source of evidence to inform the government about funding reallocation. METHODS: The study was a combined retrospective and prospective, non-randomized cohort comparison over three years of CCT and MMT in Vietnam, conducted between 2012 and 2014, involving 208 CCT participants and 384 MMT participants with heroin dependence. The primary end-point was drug-free days over three years. Total costs, including both program and participant personal costs were measured and cost-effectiveness compared. Mixed effects regression analyses were used to analyze effectiveness data and non-parametric bootstrapping method was used to compare cost effectiveness. RESULTS: Over three years, MMT costed on average VND85.73 million (US$4108) less than CCT (95% CI: -VND76.88 million, -VND94.59 million). On average, a MMT participant had 344.20 more drug-free days compared to a CCT participant (p<0.001). The incremental cost-effectiveness ratio for MMT was VND0.25 million (US$11.99) (95% CI: -VND0.34 million, -VND0.19 million) per drug free day suggesting MMT is the more cost effective alternative. CONCLUSIONS: Compared to CCT, MMT is both less expensive and more effective in achieving drug free days. If the government of Vietnam invests in MMT instead of CCT, it is potentially a cost-saving strategy for reducing illicit drug use among heroin dependent individuals. PMID- 27664553 TI - Use of and reasons for using multiple other tobacco products in daily and nondaily smokers: Associations with cigarette consumption and nicotine dependence. AB - BACKGROUND: Use of other tobacco products (OTPs) among smokers is increasing. Little is known about types of OTP used and the reasons for use, and how OTP use and reasons for use correlate with smoking patterns and nicotine dependence in daily and nondaily smokers. This paper addresses these gaps in the literature. METHODS: 656 daily smokers and 203 nondaily smokers provided information on their use of different OTPs (hookah, e-cigarettes, chew/snuff, snus, cigars, dissolvables), and reasons for using OTPs (e.g., "to cut down on smoking"), as well as their cigarette consumption and nicotine dependence. Logistic regression models assessed the association of smoking status with OTP use (ever and current) and reasons for use. Within each smoking group, separate logistic regression models examined the associations of OTP use and reasons for use with cigarette consumption and nicotine dependence. RESULTS: Compared to daily smokers, nondaily smokers were more likely to use hookah and cigars, less likely to use dissolvables, and less likely to endorse using OTPs to reduce their smoking. Among non-daily smokers, nicotine dependence was associated with a higher likelihood of current OTP use (OR=1.04 [95% CI 1.01-1.07]; p<0.05), whereas cigarette consumption was not. CONCLUSIONS: Results suggest OTP use in nondaily smokers does not correlate with less frequent smoking, but may correlate with higher nicotine dependence. Use of combustible OTPs among nondaily smokers may offset any potential benefits achieved through less frequent cigarette consumption. Providers should explicitly address OTP use when discussing cigarette cessation and reduction. PMID- 27664554 TI - Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence. AB - BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. METHODS: Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). RESULTS: Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; pcorrected=0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; pcorrected=0.041) (HC vs. NOD). CONCLUSIONS: This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. PMID- 27664555 TI - Drug-eluting balloon versus standard percutaneous transluminal angioplasty in infrapopliteal arterial disease: A meta-analysis of randomized trials. AB - BACKGROUND: Drug-eluting balloon (DEB) and standard percutaneous transluminal angioplasty (PTA) are commonly used endovascular therapeutic procedures for the revascularization of infrapopliteal arterial occlusive disease. However, which procedure is more beneficial for patients is unknown. METHODS AND RESULTS: We performed a meta-analysis, searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, ISI Web of Knowledge, and relevant websites without language or publication date restrictions for randomized trials that compared DEB with PTA in patients with infrapopliteal arterial occlusive disease. The keywords were "drug-eluting balloon," "angioplasty," "infrapopliteal," "tibial arteries," and "below the knee". We selected late lumen loss, target lesion revascularization, binary restenosis, major adverse event as the outcomes of this meta-analysis. Based on the inclusion criteria, we identified 4 prospective randomized trials. One-year outcomes did not show any significant differences between the DEB and PTA groups, respectively: target lesion revascularization (14.6% versus 22.1%; OR, 0.71; 95% CI, 0.45-1.14, P = 0.15), binary restenosis (33.3% versus 62.9%; OR, 0.40; 95% CI, 0.04-3.73, P = 0.42), late lumen loss (MD, -0.52; 95% CI, -1.52 to 0.48, P = 0.31), major adverse event (29.0% versus 38.8%; OR, 0.68; 95% CI, 0.24-1.95, P = 0.48). CONCLUSIONS: For infrapopliteal arterial occlusive disease, DEB has the same one-year benefits as PTA. There is insufficient evidence to support the superiority of either method. Further large-scale prospective randomized trials should produce more reliable results. PMID- 27664556 TI - Minimally invasive pancreaticoduodenectomy: A comprehensive review. AB - BACKGROUND: While an increasing number of open procedures are now routinely performed laparoscopically or robotically, minimally invasive pancreaticoduodenectomy (MIPD) remains one of the most challenging operations in abdomen. The aim of this study is to evaluate the current status and development of MIPD. METHODS: Embase, Medline, and PubMed databases were searched to identify studies up to and including Feb 2016 using the keywords "laparoscopic", or "laparoscopy", or "hand-assisted", or "minimally invasive", or "robotic", or "da vinci" combined with "pancreaticoduodenectomy", or "duodenopancreatectomy", "Whipple", or "pancreatic resection". Articles written in English with more than 10 cases were included for review. RESULTS: Thirty-two articles representing 2209 patients were included for review. The weighted average operative time and intraoperative blood loss was 427.3 min and 289.4 mL respectively. A total of 375 patients required conversion to open pancreaticoduodenectomy (OPD), with an overall conversion rate of 17.8%. The postoperative severe complications (the Clavien-Dindo Classification >= III) occurred in 3.8%-33.0% patients, with an overall severe morbidity of 14.3%. Particularly, the overall incidence of clinically significant postoperative pancreatic fistula (POPF) was 8.0%. There were 26 perioperative death cases in total, with an overall postoperative mortality rate of 2.3%. The weighted average number of collected lymph nodes was 17.9, and R0 resection ranged from 60.0% to 100.0%. Comparisons between MIPD and OPD showed that MIPD increased operative time, decreased intraoperative blood loss and shortened the length of hospital stay, but the overall morbidity and mortality were comparable. CONCLUSIONS: MIPD is technically feasible and safe in highly selected patients and can offer acceptable oncological outcomes. But concerns such as long-term outcomes, cost-effectiveness analysis, and learning curve analysis should be fully demonstrated before the popularization of this challenging procedure. PMID- 27664557 TI - Credentialing in surgical specialities: Recommendations by the Association of Surgeons in Training. AB - The General Medical Council (GMC) has conducted a consultation process on its proposals for "credentialing" in postgraduate medical practice in the UK. It has been suggested that these may be used to provide formal accreditation of a doctor's competency in a certain area of practice. There are 5 main issues being consulted upon: (a) the time point in a doctor's career at which credentialing should be undertaken, (b) the scope of practice that should be included in credentials and whether this should include any competency already accredited by a Certificate of Completion of Training, (c) the funding source for the credentialing process, (d) the bodies that are entitled to award a credential, and (e) who exactly should be eligible for a credential. The Association of Surgeons in Training has commented on each issue and made recommendations to the GMC. One area of practice that has already begun a regulation process is Cosmetic Surgery, in response to the lack of defined standards and a clear training pathway. Both the GMC and Royal College of Surgeons of England have now published standards in this area and will come into effect in 2016. The impact of these on surgical training is discussed. PMID- 27664558 TI - The evolving use of ECMO: The impact of the CESAR trial. AB - INTRODUCTION: To compare characteristics and outcomes of patients receiving extracorporeal membrane oxygenation (ECMO) therapy as well as medical research activities related to ECMO before and after release of preliminary results of the CESAR trial. METHODS: We assessed trends in EMCO use among adults, patient and institutional characteristics, in-hospital mortality, peri-procedural complications and resource use before and after first quarter of 2008 in Nationwide Inpatient Sample Database. Literature review was conducted to evaluate publications related to adult ECMO during the same time period. RESULTS: Overall, 8389 patients received ECMO therapy between 2001 and 2011. ECMO use remained stable between 2001 and 2007 and increased significantly from 2008 to 2011. Comparing time periods before and after first quarter of 2008, patients on ECMO in later years were more likely to be older (Before vs. After: (age 65+) 18.9% vs. 23.1%) and have two or more comorbidities (43.6% vs. 52.3%). After adjusting for patient and institutional characteristics, in-hospital mortality was comparable for the two time periods (Odds Ratio 0.76, 95% CI 0.55-1.05). Between 2001 and 2011, 652 adult ECMO related English literature were identified, published in 181 English journals and by investigators from 31 countries. There was a significant increase in number of publications after 2008. CONCLUSION: The presence of the CESAR trial was associated with significant increase in the utilization of ECMO in clinical practice and in the research activities related to ECMO. Moreover, ECMO has since been used in patients of older age and higher comorbidities, but with no increase in in-hospital mortality followed. PMID- 27664559 TI - Nomogram for 5-year relapse-free survival of a patient with advanced gastric cancer after surgery. AB - BACKGROUND: Prognoses vary substantially among patients with advanced gastric cancer following curative surgery. The aim of the current study was to develop and verify the validity of a novel nomogram that predicts the probability of 5 year relapse-free survival (RFS) in patients who underwent curative resection for stage II/III gastric cancer. MATERIALS AND METHODS: A nomogram to predict 5-year RFS following surgical resection of gastric cancer was constructed based on the data of patients who underwent surgery for primary gastric carcinoma at three institutions in Japan in January 2001-December 2006. Multivariate analysis using a Cox proportional hazards regression model was performed, and the nomogram's predictive accuracy (discrimination) and the agreement between observed outcomes and predictions (calibration) were evaluated by internal validation. RESULTS: Multivariate analyses revealed that age at operation, depth of tumor, tumor location, lymph node classification, and presence of combined resection were significant prognostic factors for RFS. In the internal validation, discrimination of the developed nomogram for 5-year RFS was superior to that of the American Joint Committee on Cancer TNM classification (concordance indices of 0.80 versus 0.67; P < 0.001). Moreover, calibration appeared to be accurate. Based on these results, we have created free software to more easily predict 5 year RFS. CONCLUSION: We developed and validated a nomogram to predict 5-year RFS after curative surgery for stage II/III gastric cancer. This tool will be useful for the assessing a patient's individual recurrence risk when considering additional therapy in clinical practice. PMID- 27664560 TI - Patient-reported adverse events after hernia surgery and socio-economic status: A register-based cohort study. AB - BACKGROUND: The aim of the present study was to assess how socio-economic background influences perception of an adverse postoperative event after hernia surgery, and to see if this affects the pattern of seeking healthcare advice during the early postoperative period. MATERIALS AND METHODS: All patients aged 15 years or older with a primary unilateral inguinal or femoral hernia repair recorded in the Swedish Hernia Register (SHR) between November 1 and December 31, 2002 were sent a questionnaire inquiring about adverse events. Data on civil status, income, level of education and ethnic background were obtained from Statistics Sweden. RESULTS: Of the 1643 patients contacted, 1440 (87.6%) responded: 1333 (92.6%) were men and 107 (7.4%) women, mean age was 59 years. There were 203 (12.4%) non-responders. Adverse events were reported in the questionnaire by 390 (27.1%) patients. Patients born in Sweden and patients with high income levels reported a significantly higher incidence of perceived adverse events (p < 0.05). Patients born in Sweden and females reported more events requiring healthcare contact. There was no association between registered and self-reported outcome and civil status or level of education. CONCLUSION: We detected inequalities related to income level, gender and ethnic background. Even if healthcare utilization is influenced by socio-economic background, careful information of what may be expected in the postoperative period and how adverse events should be managed could lead to reduced disparity and improved quality of care in the community at large. PMID- 27664561 TI - Dosage effects of extracorporeal shockwave therapy in early hip necrosis. AB - BACKGROUND: This study investigated the effects of different dosages of extracorporeal shockwave therapy (ESWT) in early osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Thirty-three patients (42 hips) were randomly divided into three groups. Group A (10 patients with 16 hips) received 2000 impulses of ESWT at 24 Kv to the affected hip. Group B (11 patients with 14 hips) and Group C (12 patients with 12 hips) received 4000 and 6000 impulses of ESWT respectively. The evaluations included clinical assessment, radiographs, dynamic contrast-enhanced MRI for microcirculation (Ktrans) and plasma volume (Vp), and blood tests for biomarker analysis (NO3, VEGF, BMP-2, osteocalcin, TNF-alpha, IL 6, substance P, CGRP, DKK-1 and IGF). RESULTS: Significant differences of pain and Harris hip scores were noticed between Group A and C in 6 months after ESWT (all P < 0.05). The pain score decreased, but not Harris hip score improved over the observation time period from 6 to 24 months. Total hip arthroplasty was performed in 3 patients (4 hips) in Group A, but none in Groups B and C. Group C showed significant changes in serum biomarkers for angiogenesis, osteogenesis, anti-inflammation, pain threshold and tissue regeneration between one week and one month after treatment (all P < 0.05). However, no significant changes in the infarction volume in image studies were noted in all groups (all P > 0.05). The post-treatment Ktrans and Vp in the peri-necrotic areas of Group B and C were significantly greater than pre-treatment data (both P < 0.05). CONCLUSIONS: High dosage ESWT is more effective in early stage ONFH. The systemic beneficial effects of ESWT may ultimately enhance angiogenesis with improvement of microcirculation of the peri-necrotic areas, that in turn, can improve subchondral bone remodeling and prevent femoral head collapse. PMID- 27664562 TI - Narrative skills in deaf children who use spoken English: Dissociations between macro and microstructural devices. AB - Previous research has highlighted that deaf children acquiring spoken English have difficulties in narrative development relative to their hearing peers both in terms of macro-structure and with micro-structural devices. The majority of previous research focused on narrative tasks designed for hearing children that depend on good receptive language skills. The current study compared narratives of 6 to 11-year-old deaf children who use spoken English (N=59) with matched for age and non-verbal intelligence hearing peers. To examine the role of general language abilities, single word vocabulary was also assessed. Narratives were elicited by the retelling of a story presented non-verbally in video format. Results showed that deaf and hearing children had equivalent macro-structure skills, but the deaf group showed poorer performance on micro-structural components. Furthermore, the deaf group gave less detailed responses to inferencing probe questions indicating poorer understanding of the story's underlying message. For deaf children, micro-level devices most strongly correlated with the vocabulary measure. These findings suggest that deaf children, despite spoken language delays, are able to convey the main elements of content and structure in narrative but have greater difficulty in using grammatical devices more dependent on finer linguistic and pragmatic skills. PMID- 27664563 TI - Long- and short-term diabetes mellitus type 1 modify young and elder rat salivary glands morphology. AB - OBJECTIVE: In this study we performed a temporal analysis of the effects of Diabetes Mellitus on morphology and laminin deposition in salivary glands of young (2 months-old) and aging (12 months-old) male Wistar rats, using immunohistochemistry. MATERIALS AND METHODS: The animals were divided in control and diabetic (Streptozotocin induced) groups and euthanized after short and long term diabetes induction. RESULTS: Short-term induction led to vacuolization of parotid acinar cells and increased laminin deposition in both animal ages. In young rats, no difference was observed between short or long-term diabetes regarding laminin deposition, but parotid acinar cells vacuolization was more discrete after long-term diabetes. A slight decrease of submandibular gland convoluted granular ducts was observed in young and elder diabetic animal ages. In diabetic aging rats was observed an increase of laminin content only in the parotid gland. CONCLUSIONS: These results suggest that some Diabetes Mellitus effects on salivary glands are not progressive over time, possibly due to the existence of adaptive mechanisms in response to chronic hyperglycemia. They also show that the duration of the disease was more relevant to the morphological effects than the age, although it is known that aging per se affects salivary gland morphology and function. PMID- 27664565 TI - Drinking motives and PTSD-related alcohol expectancies among combat veterans. AB - INTRODUCTION: Combat veterans are at increased risk for PTSD and alcohol misuse, and expectancies and motives for drinking may help explain the link between these comorbid issues. This investigation explored the relationships between PTSD symptoms, PTSD-related alcohol expectancies, motives for drinking, and alcohol consumption/misuse. METHOD: 67 veterans of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) participated in this project. We examined correlations between PTSD severity, alcohol misuse, drinking motives, PTSD alcohol expectancies, and tested models of mediation and moderation. RESULTS: Coping-anxiety drinking motives and positive PTSD-related alcohol expectancies were associated with alcohol misuse and alcohol-related consequences, but not with consumption. Each PTSD symptom cluster was associated with positive and negative PTSD alcohol expectancies, and coping-anxiety was specifically related to reexperiencing and avoidance. Drinking to cope mediated the relationship between PTSD symptoms and hazardous drinking. Moderation analyses showed that a positive relationship between PTSD severity and hazardous drinking existed among those with moderate and higher levels of positive PTSD alcohol expectancies. DISCUSSION: Our findings point to surprising, and in some cases complex, relationships between PTSD and alcohol use. Although related, PTSD alcohol expectancies and drinking motives seem to function differently in the relationship between PTSD and alcohol misuse. PMID- 27664564 TI - The role of mindfulness as approach-based coping in the PTSD-substance abuse cycle. PMID- 27664566 TI - Enhanced phase contrast transfer using ptychography combined with a pre-specimen phase plate in a scanning transmission electron microscope. AB - The ability to image light elements in both crystalline and noncrystalline materials at near atomic resolution with an enhanced contrast is highly advantageous to understand the structure and properties of a wide range of beam sensitive materials including biological specimens and molecular hetero structures. This requires the imaging system to have an efficient phase contrast transfer at both low and high spatial frequencies. In this work we introduce a new phase contrast imaging method in a scanning transmission electron microscope (STEM) using a pre-specimen phase plate in the probe forming aperture, combined with a fast pixelated detector to record diffraction patterns at every probe position, and phase reconstruction using ptychography. The phase plate significantly enhances the contrast transfer of low spatial frequency information, and ptychography maximizes the extraction of the phase information at all spatial frequencies. In addition, the STEM probe with the presence of the phase plate retains its atomic resolution, allowing simultaneous incoherent Z contrast imaging to be obtained along with the ptychographic phase image. An experimental image of Au nanoparticles on a carbon support shows high contrast for both materials. Multislice image simulations of a DNA molecule shows the capability of imaging soft matter at low dose conditions, which implies potential applications of low dose imaging of a wide range of beam sensitive materials. PMID- 27664568 TI - Osteomalacia induced by long-term low-dose adefovir dipivoxil: Clinical characteristics and genetic predictors. AB - CONTEXT: Adefovir dipivoxil (ADV) was an important cause of adult-onset hypophosphatemic osteomalacia. However, its clinical characteristics and mechanisms have not been well defined. OBJECTIVE: The objective of the study was to summarize the clinical characteristics of ADV-induced osteomalacia and to explore the association between ADV-associated tubulopathy and polymorphisms in genes encoding drug transporters. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURE: Seventy-six affected patients were clinically studied. The SLC22A6 and ABCC2 genes were screened and compared with healthy people from the HapMap. RESULTS: Hypophosphatemia, high serum alkaline phosphatase (ALP) levels, hypouricemia, nondiabetic glycosuria, proteinuria, metabolic acidosis and high bone turnover markers were the main metabolic characteristics. Fractures and pseudofractures occurred in 39 patients. Stopping ADV administration, supplementing calcitriol and calcium was effective during the follow-up period. Single SNP analysis revealed a higher percentage of the G/A genotype at c.2934 in exon 22 of the ABCC2 gene (rs3740070) in patients than in healthy people (12% [7 of 58 patients] vs. 0% [0 of 45 patients]; P=0.017), while there was no subject with homozygosity for the A allele at c.2934. CONCLUSIONS: ADV can be nephrotoxic at a conventional dosage. The G/A genotype at c.2934 of the ABCC2 gene may be a predictor of patients at greater risk for developing ADV-associated tubulopathy. Larger case-control studies are needed to further verify this finding. PMID- 27664567 TI - Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade. AB - Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis work in concert to control many stages of this process, and when one is impaired it leads to failure of bone healing, termed a nonunion. During fracture repair, there is an infiltration of immune cells at the fracture site that not only mediate the inflammatory responses, but we hypothesize they also exert influence on neovasculature. Thus, further understanding the effects of immune cell participation throughout fracture healing will reveal additional knowledge as to why some fractures heal while others form nonunions, and lead to development of novel therapeutics modulating immune cells, to increase fracture healing and prevent nonunions. Using novel femoral segmental and critical-size defect models in mice, we identified a systemic and significant increase in immature myeloid cell (IMC) infiltration during the initial phase of fracture healing until boney union is complete. Using gemcitabine to specifically ablate the IMC population, we confirmed delayed bone healing. Further, adoptive transfer of IMC increased bone growth in a nonunion model, signifying the role of this unique cell population in fracture healing. We also identified IMC post-fracture have the ability to increase endothelial cell migration, and tube formation, signaling the essential communication between the immune system and angiogenesis as a requirement for proper bone healing. Based on this data we propose that IMC may play a significant role in fracture healing and therapeutic targeting of IMC after fracture would minimize the chances of eventual nonunion pathology. PMID- 27664569 TI - High-school predictors of university achievement: Youths' self-reported relationships with parents, beliefs about success, and university aspirations. AB - Associations between youths' reported relationships with their parents, beliefs about how success is attained, educational aspirations, and university completion were examined. Data come from the German Socioeconomic Panel. At age 17, youth (n = 3284) reported on their relationships with their parents, beliefs about success, and educational aspirations. University completion was assessed up to eight years later. At age 17, perceptions of parental warmth and interest in youths' academics were associated with beliefs that success is due to merit (positively) and that success is due to external factors or dominance over others (negatively). Beliefs that success is due to merit and external factors were associated with educational aspirations positively and negatively respectively. Educational aspirations positively predicted university completion up to eight years later. Relationships with parents had stronger associations with achievement when parents completed a university degree; beliefs about success had stronger associations with aspirations when parents did not. PMID- 27664570 TI - Azithromycin modulates immune response of human monocyte-derived dendritic cells and CD4+ T cells. AB - Azithromycin (AZM) is a macrolide antibiotic that exhibits anti-inflammatory activity aside from its antimicrobial effect, a feature that may ameliorate certain inflammatory disorders and prevent graft-versus-host disease in patients receiving stem cell transplantation. In the present study, we investigated the ability of AZM to influence the function of human monocyte-derived dendritic cells (DCs) and CD4+ T cells. We found that AZM down-regulated CD80, CD86, and HLA-DR expression in lipopolysaccharide (LPS)-stimulated DCs and suppressed interleukin (IL)-6, IL-10, IL-12, and tumor necrosis factor-alpha production in these cells. In addition, AZM increased endocytosis and/or expression of Toll like receptor (TLR)2, TLR4, and TLR9 in DCs and suppressed anti-CD3/CD28-induced CD4+ T cell proliferation and interferon-gamma production, an effect that was synergistic with dexamethasone. Finally, AZM suppressed DC-induced allogeneic T cell proliferation and cytokine production. Our study demonstrates that AZM modulates DC and CD4+ T cell function and may be of therapeutic benefit in various inflammatory disorders. PMID- 27664571 TI - Preoperative neutrophil-to-lymphocyte ratio is a more valuable prognostic factor than platelet-to-lymphocyte ratio for nonmetastatic rectal cancer. AB - Several combinations of inflammatory factors, including neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors in various malignant tumors, including colorectal cancer (CRC). The aim of this study was to evaluate the prognostic value of NLR and PLR for patients with rectal cancer (RC) who underwent curative surgery. Data from patients who underwent curative resection for RC were retrospectively reviewed. The cutoff for NLR and PLR was defined as 2.3 and 144 by receiver operating characteristic (ROC) curve. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier method. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. A total of 140 patients were eligible in the study. High NLR (>2.3) and high PLR (>144) both predicted lower OS and DFS according to Kaplan-Meier method. But in the multivariable Cox regression model, only the high NLR retained significance for reduced OS and DFS. According to Chi-square test, patients with higher NLR had larger tumor size and higher pN-stage. While PLR was only associated with the pN stage. High preoperative NLR was shown to be a negative independent prognostic factor in patients undergoing resection for nonmetastatic RC. It may be helpful as a factor to guide the postoperative therapies. PMID- 27664572 TI - The changing face of cardiovascular disease 2000-2012: An analysis of the world health organisation global health estimates data. AB - The pattern and global burden of disease has evolved considerably over the last two decades, from primarily communicable, maternal, and perinatal causes to non communicable disease (NCD). Cardiovascular disease (CVD) has become the single most important and largest cause of NCD deaths worldwide at over 50%. The World Health Organisation (WHO) estimates that 17.6 million people died of CVD worldwide in 2012. Proportionally, this accounts for an estimated 31.43% of global mortality, with ischaemic heart disease (IHD) accounting for approximately 7.4 million deaths, 13.2% of the total. IHD was also the greatest single cause of death in 2000, accounting for an estimated 6.0 million deaths. The global burden of CVD falls, principally, on the low and middle-income (LMI) countries, accounting for over 80% of CVD deaths. Individual populations face differing challenges and each population has unique health burdens, however, CVD remains one of the greatest health challenges both nationally and worldwide. PMID- 27664573 TI - Acute thrombotic left main coronary artery; treatment with low dose slow infusion tPA. PMID- 27664574 TI - End-stage renal disease patients on chronic maintenance hemodialysis in a hospitalized acute heart failure cohort: Prevalence, clinical characteristics, therapeutic options, and mortality. PMID- 27664575 TI - Does a blue crab putative insulin-like peptide binding protein (ILPBP) play a role in a virus infection? AB - Insulin-like peptides (ILPs) have regulatory roles in reproduction, development and metabolism in invertebrates. The mode of ILP actions has not been well studied in invertebrates in regard to the role of binding partners, i.e., ILP binding protein (ILPBP). In this study, the full-length cDNA of Callinectes sapidus ILPBP (Cas-ILPBP, 960 bp) has been isolated using RACE cloning, having short 5' and 3' UTRs of 30 and 162 bp, respectively. The predicted precursor of Cas-ILPBP (255 aa) contains, in order a signal peptide (23 aa), an insulin-like growth factor (IGF) binding (IB) domain (79 aa), a kazal-type serine protease inhibitor (KI) domain (36 aa) and an immunoglobulin (Ig) domain (101 aa). Phylogenetic analysis shows that Cas-ILPBP is grouped with the ILPBPs of other crustacean species, and it shares the closest relationship with the ILPBP from another crab species, Scylla paramamosain. Transcripts of Cas-ILPBP are found in all examined tissues, with the highest levels in the nervous tissues (eyestalk ganglia, brain and thoracic ganglia complex) and followed by midgut, the pericardial organ, abdominal muscle and the heart. As Cas-ILPBP contains a putative Ig domain, it is hypothesized that this protein may be involved in immunity, particularly in the adult females infected with a reo-like virus (CsRV1). The expression levels of Cas-ILPBP are examined in several tissues (hemocytes, midgut, eyestalk ganglia) from the animals carrying varying levels of CsRV1 at 17 and 23 degrees C water temperatures. Cas-ILPBP levels in the midgut are most significantly affected by high levels of CsRV1 infection. Reduction in Cas-ILPBP levels in the midguts is noted from the animals infected with high levels of CsRV1 that show reduced or stop feeding activity, indicating that it may play an important role in midgut functions such as digestion and nutrient absorption. PMID- 27664576 TI - Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. AB - Low-level formaldehyde exposure is inevitable in industrialized countries. Although daily-life formaldehyde exposure level is practically impossible to induce cell death, most of mechanistic studies related to formaldehyde toxicity have been performed in cytotoxic concentrations enough to trigger cell death mechanism. Currently, toxicological mechanisms underlying the sub-cytotoxic exposure to formaldehyde are not clearly elucidated in skin cells. In this study, the genome-scale transcriptional analysis in normal human keratinocytes (NHKs) was performed to investigate cutaneous biological pathways associated with daily life formaldehyde exposure. We selected the 175 upregulated differentially expressed genes (DEGs) and 116 downregulated DEGs in NHKs treated with 200MUM formaldehyde. In the Gene Ontology (GO) enrichment analysis of the 175 upregulated DEGs, the endoplasmic reticulum (ER) unfolded protein response (UPR) was identified as the most significant GO biological process in the formaldeyde treated NHKs. Interestingly, the sub-cytotoxic formaldehyde affected NHKs to upregulate two enzymes important in the cellular transsulfuration pathway, cystathionine gamma-lyase (CTH) and cystathionine-beta-synthase (CBS). In the temporal expression analysis, the upregulation of the pro-inflammatory DEGs such as MMP1 and PTGS2 was detected earlier than that of CTH, CBS and other ER UPR genes. The metabolites of CTH and CBS, l-cystathionine and l-cysteine, attenuated the formaldehyde-induced upregulation of pro-inflammatory DEGs, MMP1, PTGS2, and CXCL8, suggesting that CTH and CBS play a role in the negative feedback regulation of formaldehyde-induced pro-inflammatory responses in NHKs. In this regard, the sub-cytotoxic formaldehyde-induced CBS and CTH may regulate inflammation fate decision to resolution by suppressing the early pro inflammatory response. PMID- 27664577 TI - Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters. AB - Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100nM and 300nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circumvented by the second generation taxane SB-T-1216. Moreover, we demonstrated that it was not possible to establish sublines of SK-BR-3 and MCF-7 cells resistant to this taxane. It means that at least the tested breast cancer cells are unable to develop resistance to some taxanes. Employing mRNA expression profiling of all known human ABC transporters and subsequent Western blot analysis of the expression of selected transporters, we demonstrated that only the ABCB1/PgP and ABCC3/MRP3 proteins were up-regulated in both paclitaxel-resistant sublines. We found up regulation of ABCG2/BCRP and ABCC4 proteins only in paclitaxel-resistant SK-BR-3 cells. In paclitaxel-resistant MCF-7 cells, ABCB4/MDR3 and ABCC2/MRP2 proteins were up-regulated. Silencing of ABCB1 expression using specific siRNA increased significantly, but did not completely restore full sensitivity to both paclitaxel and doxorubicin. Thus we showed a key, but not exclusive, role for ABCB1 in mechanisms of paclitaxel resistance. It suggests the involvement of multiple mechanisms in paclitaxel resistance in tested breast cancer cells. PMID- 27664579 TI - Comparison of Times to Ureteral Efflux after Administration of Sodium Fluorescein and Phenazopyridine. AB - PURPOSE: There is currently a national shortage of indigo carmine. In efforts to identify the most efficient aid for visualizing ureteral efflux intraoperatively we investigated the time to excretion of phenazopyridine vs a newly identified alternative, sodium fluorescein. MATERIALS AND METHODS: We analyzed prospectively collected data on a cohort of women who underwent pelvic reconstructive surgery in 2015. Per provider preference patterns a number of patients were administered 200 mg phenazopyridine orally with a sip of water 1 hour prior to the start of operative time. Other patients were given 0.5 ml 10% sodium fluorescein intravenously in the operating room. In all cases time was measured between the administration of the agent and the visualization of color changes consistent with agent efflux in an indwelling catheter, which was placed at the start of the operation. Differences in excretion times between the groups were compared with the Wilcoxon rank sum test. RESULTS: Seven women received phenazopyridine and 5 received sodium fluorescein. Mean excretion time was significantly longer in the phenazopyridine group compared to the sodium fluorescein group (81.9 vs 5.1 minutes, p = 0.0057). Median excretion time for phenazopyridine was 70 minutes (range 59 to 127) and for sodium fluorescein it was 5 minutes (range 3 to 9). CONCLUSIONS: Sodium fluorescein is excreted significantly faster in the operating room compared to phenazopyridine. Depending on the cost of these agents at an institution, in addition to the desire to decrease operative time, this may impact practice patterns and agent selection. PMID- 27664578 TI - Upper Urinary Tract Carcinoma In Situ: Current Knowledge, Future Direction. AB - PURPOSE: Carcinoma in situ of the urinary tract is a high grade form of nonmuscle invasive urothelial cancer. Our understanding of this entity in the upper tract is poor, and case management remains challenging due to knowledge gaps regarding the definition, diagnosis, treatment options and followup of the disease. We reviewed the available literature for similarities and differences between bladder and upper tract carcinoma in situ, and herein summarize the best available data. MATERIALS AND METHODS: We reviewed PubMed(r) and MEDLINETM databases from January 1976 through September 2014. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was used to screen publications. All authors participated in the development of a consensus definition of disease. RESULTS: A total of 61 publications were found suitable for this review. All studies were retrospective. Compared to bladder carcinoma in situ, upper tract carcinoma in situ appears to have lower progression rates and improved survival. All available studies demonstrate topical therapy to be effective in treating upper tract carcinoma in situ, with decreased recurrence rates compared to bladder carcinoma in situ. Highlighted areas of current knowledge gaps include variable definitions of disease, methods of drug delivery and ideal treatment course. Improving methods for detection may allow easier diagnosis and more effective treatment. CONCLUSIONS: Based on the available data, organ preserving therapy with topical agents is an alternative to radical surgery in select patients with upper tract carcinoma in situ, although this method has not been evaluated in prospective trials. A paradigm shift regarding detection and treatment is needed to improve care and allow better renal preservation. A consensus definition of the disease is offered, and several areas of major knowledge gaps and opportunities for future research are identified. PMID- 27664580 TI - Tolerability of Repeat Use of Blue Light Cystoscopy with Hexaminolevulinate for Patients with Urothelial Cell Carcinoma. AB - PURPOSE: Hexaminolevulinate hydrochloride with blue light cystoscopy is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy for the detection of urothelial cell carcinoma. In this study we examined the tolerability of the repeat use of white light cystoscopy with blue light cystoscopy. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride during a 34-month period at 2 institutions. We compared the incidence of adverse events after initial and subsequent procedures. We grouped, graded and assigned the degree of attribution for all adverse events. RESULTS: A total of 180 patients underwent 269 white light cystoscopy with blue light cystoscopy procedures. Of those 180 patients 118 (65%) underwent white light cystoscopy with blue light cystoscopy only 1 time. The other 62 (35%) patients underwent white light cystoscopy with blue light cystoscopy 2 or more times, including 43 (24%) 2 times and 19 (10%) 3 or more times. We noted 89 adverse events out of 269 procedures (33%), of which 66 (74%) occurred after the first white light cystoscopy with blue light cystoscopy; 14 (16%) after the second time and 9 (10%) after the third time or more. We found no statistically significant difference in adverse events between those patients undergoing 1 vs 2 or more white light cystoscopy with blue light cystoscopy procedures (p=0.134). We observed 1 grade 3 adverse event and no grade 4 or 5 adverse events. None of the adverse events were classified as probably or definitely related to hexaminolevulinate hydrochloride. CONCLUSIONS: In this retrospective study we found no statistically significant difference in the frequency or the grade of adverse events between first and repeat use of white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride. PMID- 27664581 TI - Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis. AB - PURPOSE: Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. RESULTS: Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. CONCLUSIONS: We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. PMID- 27664582 TI - Nerve growth factor-induced plasticity in medial prefrontal cortex interneurons of aged Wistar rats. AB - The medial prefrontal cortex (mPFC) has been identified as a critical center for working and long-term memory. In this study, we have examined the expression of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in mPFC interneurons and the density of the mPFC cholinergic and dopaminergic innervation in cognitively-impaired aged Wistar rats. We also tested the possibility that the potential age-related changes might rely on insufficient neurotrophic support. The total number of NPY- and VIP-immunoreactive neurons and the density of vesicular acetylcholine transporter (VAChT)- and tyrosine hydroxylase (TH) immunoreactive varicosities were estimated using stereological methods. The number of NPY-immunoreactive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased expression of NPY was fully reversed by intracerebroventricular administration of nerve growth factor. No differences in the density of VAChT- and TH immunoreactive varicosities were found among all groups. Our results indicate that the reduced expression of NPY in the mPFC of aged rats can be ascribed to the age-associated loss of neurotrophic support, and raise the possibility that these changes might contribute for the cognitive decline that occurs during non pathological aging. PMID- 27664583 TI - Functions of synapse adhesion molecules neurexin/neuroligins and neurodevelopmental disorders. AB - Neurexins and neuroligins are two distinct families of single-pass transmembrane proteins localized at pre- and postsynapses, respectively. They trans synaptically interact with each other and induce synapse formation and maturation. Common variants and rare mutations, including copy number variations, short deletions, and single or small nucleotide changes in neurexin and neuroligin genes have been linked to the neurodevelopmental disorders, such as autism spectrum disorders (ASDs). In this review, we summarize the structure and basic synaptic function of neurexins and neuroligins, followed by behaviors and synaptic phenotypes of knock-in and knock-out mouse of these family genes. From the studies of these mice, it turns out that the effects of neurexins and neuroligins are amazingly neural circuit dependent, even within the same brain region. In addition, neurexins and neuroligins are commonly involved in the endocannabinoid signaling. These finding may provide not only insight into understanding the pathophysiology, but also the concept for strategy of therapeutic intervention for ASDs. PMID- 27664584 TI - microRNAs target SRSF7 splicing factor to modulate the expression of osteopontin splice variants in renal cancer cells. AB - SRSF7 is a SR splicing factor involved in the regulation of splicing and mRNA export of cancer-related genes. The mechanisms regulating the expression of SRSF7 are unknown. This study shows that SRSF7 expression in cancer cells is regulated by microRNAs: short, non-coding RNAs that bind to 3'UTR of target genes and downregulate their expression. We show that microRNAs miR-30a-5p and miR-181a-5p together with SRSF7 form regulatory feedback loop in which the expression of microRNAs is recurrently regulated by its target. Finally, we demonstrate that silencing of SRSF7 affects the expression of osteopontin splice variants and decreases proliferation rate of renal cancer cells. PMID- 27664585 TI - Characterization of a novel acquired der(1)del(1)(p13p31)t(1;15)(q42;q15) in a high risk t(12;21)-positive acute lymphoblastic leukemia. AB - The t(12;21)(p13;q22) with ETV6-RUNX1 fusion occurs in 25% of cases of B-cell precursor acute lymphoblastic leukemia (BCP-ALL); and is generally associated with favorable prognosis. However, 15-20% of the t(12;21)-positive cases are associated with high-risk disease due to for example slow early responses to therapy. It is well-known that development of overt leukemia in t(12;21)-positive ALL requires secondary chromosomal aberrations although the full spectrum of these cytogenetic alterations is yet unsettled, and also, how they may be associated with disease outcome. This report describes the case of an adolescent male with t(12;21)-positive ALL who displayed a G-banded karyotype initially interpreted as del(1)(p22p13) and del(15)(q15). The patient was treated according to NOPHO standard risk protocol at diagnosis, but had minimal residual disease (MRD) at 6,4% on day 29 as determined by flow cytometric immunophenotyping. Because of MRD level>0.1% he was then assigned as a high risk patient and received intensified chemotherapy accordingly. Further molecular cytogenetic studies and oligo-based aCGH (oaCGH) analysis characterized the acquired complex structural rearrangements on chromosomes 1 and 15, which can be described as der(1)del(1)(p13.1p31.1)t(1;15)(q42;q15) with concurrent deletions at 1q31.2 q31.3, 1q42.12-q43, and 15q15.1-q15.3. The unbalanced complex rearrangements have not been described previously. Extended locus-specific FISH analyses showed that the three deletions were on the same chromosome 1 homologue that was involved in the t(1;15), and that the deletion on chromosome 15 also was on the same chromosome 15 homologue as involved in the t(1;15). Together these findings show the great importance of the combined usage of molecular cytogenetic analyses and oaCGH analysis to enhance characterization of apparently simple G-banded karyotypes, and to provide a more complete spectrum of secondary chromosomal aberrations in high risk t(12;21)-positive BCP-ALLs. PMID- 27664586 TI - Meeting report for Odd Pols 2016: Ann Arbor 2.0. AB - The Tenth International Conference on Transcription by RNA Polymerases I, III, IV and V (the 'Odd Pols') was held June 24-28, 2016 at the University of Michigan, Ann Arbor, USA and organized by David Engelke, Deborah Johnson, Richard Maraia, Lawrence Rothblum, David Schneider, Andrzej Wierzbicki and Astrid Engel. The organizers are grateful for the support from the Rackham Graduate School of the University of Michigan for providing the meeting venue. The environment provided a great background with unexpected encounters with fireflies, free live music and a festive fireworks display. The meeting was composed of eleven oral sessions and a poster session. The keynote speaker, Dave Engelke, opened the meeting with his presentation entitled "A personal history of pol III transcription - how we got here from the 'good old days'." The meeting drew attendees from sixteen countries that shared their research discoveries. Here we present some of the highlights from the meeting using summaries provided by the participants. PMID- 27664587 TI - The evolutionary divergence of STAT transcription factor in different Anopheles species. AB - Anopheles mosquito transmits Plasmodium, the malaria causing parasite. Different species of Anopheles mosquito dominate in a particular geographical location and are capable of transmitting specific strains of Plasmodium. It is important to understand the biology of different anophelines to control the parasite transmission. STAT is an evolutionary conserved transcription factor that regulates the parasite development in African malaria vector Anopheles gambiae. Unlike Drosophila and Aedes aegypti, where a single STAT gene plays an important role in immunity, An. gambiae contains one evolutionary conserved STAT-A and another retro-duplicated, introns-less STAT-B gene. To find out whether other species of Anopheles also have two STATs, the available genomic data of different anophelines were used to annotate their STATs through in silico analyses. Our results revealed that Indian malaria vector An. stephensi genome contains two STATs, AsSTAT-A and AsSTAT-B genes. These genes were cloned and confirmed by sequencing. Both AsSTATs were found to be expressed in different development stages of mosquito. However, the relative mRNA levels of evolutionary conserved AsSTAT-A gene were always higher than the retroduplicated AsSTAT-B gene. STAT pathway was activated upon Plasmodium berghei infection, indicated its role in immunity. Furthermore, comparative in silico analysis of eighteen Anopheles species revealed that five species: An. sinensis, An. albimanus, An. darlingi, An. dirus andAn. farauti do not contain STAT-B gene in their genome. Interestingly, thirteen species of the subgenus Anopheles and Cellia that contain both STATs were also mutually diverged. This consequence leads to sequence variability in some significant protein motifs within the STAT-B genes. Phylogenetic analyses indicated that an independent, lineage-specific duplication occurred in the subgenus Cellia after the diversification of series Neomyzomyia from its last common ancestor. In An. atroparvus (subgenus Anopheles), STAT gene underwent recent lineage-specific duplication and give rise to a highly similar STAT-B gene. This suggested that the genetic divergence in various Anopheles species might appeared due to their adaptations to the altered environmental conditions or pathogen encounters. PMID- 27664588 TI - Influence of glucagon-like peptide 2 on energy homeostasis. AB - Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released from enteroendocrine L-type cells together with glucagon like peptide-1 in response to dietary nutrients. GLP-2 acts through a specific receptor, the GLP-2 receptor, mainly located in the gut and in the brain. Classically, GLP-2 is considered a trophic hormone involved in the maintenance of intestinal epithelial morphology and function. This role has been targeted for therapies promoting repair and adaptive growth of the intestinal mucosa. Recently, GLP-2 has been shown to exert beneficial effects on glucose metabolism specially in conditions related to increased uptake of energy, such as obesity. Several actions of GLP-2 are related to a positive energy balance: GLP-2 increases not only the absorptive surface, but also expression and activity of epithelial brush-border nutrient transporters and digestive enzymes, intestinal blood flow, postprandial chylomicron secretion and it inhibits gastrointestinal motility, providing the opportunity to increase absorption of nutrients. Other actions, including anorexigenic effects, appear in opposition to the energy intake. In this review, we discuss the GLP-2 functions related to energy homeostasis. GLP-2 could be considered an hormone causing positive energy balance, which, however has the role to mitigate the metabolic dysfunctions associated with hyper-adiposity. PMID- 27664589 TI - Structure prediction and functional analysis of a non-permutated lectin from Dioclea grandiflora. AB - Legume lectins have been widely studied and applied for many purposes in the last few decades, but many of their physiological aspects remain elusive. The Diocleinae legume subtribe, which includes intensively explored lectins, such as ConA, presents an unusual and extensive post-translational process which results in minor alterations in protein structure, in turn making its function elusive. Despite previous reports about Diocleinae precursor activity, no structural or functional analyses have ever been carried out to understand the impacts of post translational processing relative to lectin structure and binding specificity. Here we analyzed the functionality of a non glycosylated, recombinantly expressed lectin precursor from Dioclea grandiflora through inhibition assays, corroborating the experimental data with structural information generated by molecular modeling, docking calculations and molecular dynamics simulations. We demonstrate that Diocleinae precursors are active and share the same carbohydrate specificity as mature lectins. At the same time, however, subtle structural alterations were detected and mostly result in an "incomplete" functionality of the precursor, as consequence of an immature binding site and an unstructured tetramer interface, affecting carbohydrate binding and oligomer formation, respectively. PMID- 27664591 TI - Evidence and Evidence Gaps in Adolescent Health. PMID- 27664590 TI - Macrophages activate iNOS signaling in adventitial fibroblasts and contribute to adventitia fibrosis. AB - A large amount of NO is generated through the inducible nitric oxide synthase (iNOS) pathway from the vascular adventitia in various vascular diseases. However, it is currently not fully understood how the iNOS signaling pathway is activated. In the present study, this question was addressed in the context of adventitial cellular interactions. A rat model of acute hypertension in the contralateral carotid arteries was established through transverse aortic constriction (TAC) surgery. In this model, activated macrophages were found surrounded by a large quantity of iNOS-expressing adventitial fibroblasts (AFs), suggesting a possible causal relationship between macrophages and iNOS activation of the neighboring AFs. In an in vitro model, a macrophage-like cell line RAW 264.7 was first activated by LPS treatment. The supernatant was then harvested and applied to treat primary rat AFs. iNOS in AFs was activated robustly by the supernatant treatment but not by LPS itself. Treating AFs with interleukin-1beta (IL-1beta) also activated iNOS signaling, suggesting that the IL-1beta pathway might be a possible mediator. As a consequence of the iNOS activation, total protein nitration and S-nitrosylation significantly increased in those AFs. Additionally, increased deposition of type I and type III collagens was observed in both in vitro and in vivo models. The collagen deposition was partially restored by an iNOS inhibitor, 1400 W. These findings highlight the importance of iNOS signaling during vascular inflammation, and advance our understanding of its activation through a cellular interaction perspective. PMID- 27664592 TI - Improving Adolescent Sexual and Reproductive Health: A Systematic Review of Potential Interventions. AB - Adolescents have special sexual and reproductive health needs (whether or not they are sexually active or married). This review assesses the impact of interventions to improve adolescent sexual and reproductive health (including the interventions to prevent female genital mutilation/cutting [FGM/C]) and to prevent intimate violence. Our review findings suggest that sexual and reproductive health education, counseling, and contraceptive provision are effective in increasing sexual knowledge, contraceptive use, and decreasing adolescent pregnancy. Among interventions to prevent FGM/C, community mobilization and female empowerment strategies have the potential to raise awareness of the adverse health consequences of FGM/C and reduce its prevalence; however, there is a need to conduct methodologically rigorous intervention evaluations. There was limited and inconclusive evidence for the effectiveness of interventions to prevent intimate partner violence. Further studies with rigorous designs, longer term follow-up, and standardized and validated measurement instruments are required to maximize comparability of results. Future efforts should be directed toward scaling-up evidence-based interventions to improve adolescent sexual and reproductive health in low- and middle-income countries, sustain the impacts over time, and ensure equitable outcomes. PMID- 27664594 TI - Adolescent Health and Well-Being: Background and Methodology for Review of Potential Interventions. AB - Owing to child survival initiatives around the world in the 1970s and 1980s, a dramatic rise in the population of adolescents has been seen, especially in the developing countries. A quarter of world's population in 2012 comprised adolescents and young adults; of these, 90% lived in low- and middle-income countries. More recently, there has been a consensus on investing in adolescent health and development for the success of post-2015 developmental agenda. In this series of articles, we aimed to assess various interventions identified in our conceptual framework to evaluate their effectiveness in improving adolescent health. We took a systematic approach to consolidate the existing evidence. This article is an introductory article detailing the background, conceptual framework, and methodology used for synthesizing evidence, followed by seven articles summarizing evidence on interventions for sexual/reproductive health, nutrition, immunization, mental health, substance abuse, and accidents/injury. The concluding article of the series summarizes the findings of the all the previous articles in the series and the relevance of the evidence for action in the post-2015 Millennium Development Goals era along with evidence gaps and future research priorities. PMID- 27664593 TI - Interventions to Improve Adolescent Nutrition: A Systematic Review and Meta Analysis. AB - Adequate adolescent nutrition is an important step for optimal growth and development. In this article, we systematically reviewed published studies till December 2014 to ascertain the effectiveness of interventions to improve adolescent nutrition. We found one existing systematic review on interventions to prevent obesity which we updated and conducted de novo reviews for micronutrient supplementation and nutrition interventions for pregnant adolescents. Our review findings suggest that micronutrient supplementation among adolescents (predominantly females) can significantly decrease anemia prevalence (relative risk [RR]: .69; 95% confidence interval [CI]: .62-.76) while interventions to improve nutritional status among "pregnant adolescents" showed statistically significant improved birth weight (standard mean difference: .25; 95% CI: .08 .41), decreased low birth weight (RR: .70; 95% CI: .57-.84), and preterm birth (RR: .73; 95% CI: .57-.95). Interventions to promote nutrition and prevent obesity had a marginal impact on reducing body mass index (standard mean difference: -.08; 95% CI: -.17 to .01). However, these findings should be interpreted with caution due to significant statistical heterogeneity. PMID- 27664595 TI - Systematic Review and Meta-Analysis of Interventions to Improve Access and Coverage of Adolescent Immunizations. AB - Vaccination strategies are among the most successful and cost-effective public health strategies for preventing disease and death. Until recently, most of the existing immunization programs targeted infants and children younger than 5 years which have successfully resulted in reducing global infant and child mortality. Adolescent immunization has been relatively neglected, leaving a quarter of world's population underimmunized and hence vulnerable to a number of preventable diseases. In recent years, a large number of programs have been launched to increase the uptake of different vaccines in adolescents; however, the recommended vaccination coverage among the adolescent population overall remains very low, especially in low- and middle-income countries. Adolescent vaccination has received significantly more attention since the advent of the human papillomavirus (HPV) vaccine in 2006. However, only half of the adolescent girls in the United States received a single dose of HPV vaccine while merely 43% and 33% received two and three doses, respectively. We systematically reviewed literature published up to December 2014 and included 23 studies on the effectiveness of interventions to improve immunization coverage among adolescents. Moderate-quality evidence suggested an overall increase in vaccination coverage by 78% (relative risk: 1.78; 95% confidence interval: 1.41 2.23). Review findings suggest that interventions including implementing vaccination requirement in school, sending reminders, and national permissive recommendation for adolescent vaccination have the potential to improve immunization uptake. Strategies to improve coverage for HPV vaccines resulted in a significant decrease in the prevalence of HPV by 44% and genital warts by 33%; however, the quality of evidence was low. Analysis from single studies with low- or very low-quality evidence suggested significant decrease in varicella deaths, measles incidence, rubella susceptibility, and incidence of pertussis while the impact was nonsignificant for incidence of mumps with their respective vaccines. Further rigorous evidence is needed to evaluate the effectiveness of strategies to improve immunization uptake among adolescents from low- and middle-income countries. PMID- 27664596 TI - Interventions for Adolescent Mental Health: An Overview of Systematic Reviews. AB - Many mental health disorders emerge in late childhood and early adolescence and contribute to the burden of these disorders among young people and later in life. We systematically reviewed literature published up to December 2015 to identify systematic reviews on mental health interventions in adolescent population. A total of 38 systematic reviews were included. We classified the included reviews into the following categories for reporting the findings: school-based interventions (n = 12); community-based interventions (n = 6); digital platforms (n = 8); and individual-/family-based interventions (n = 12). Evidence from school-based interventions suggests that targeted group-based interventions and cognitive behavioral therapy are effective in reducing depressive symptoms (standard mean difference [SMD]: -.16; 95% confidence interval [CI]: -.26 to .05) and anxiety (SMD: -.33; 95% CI: -.59 to -.06). School-based suicide prevention programs suggest that classroom-based didactic and experiential programs increase short-term knowledge of suicide (SMD: 1.51; 95% CI: .57-2.45) and knowledge of suicide prevention (SMD: .72; 95% CI: .36-1.07) with no evidence of an effect on suicide-related attitudes or behaviors. Community-based creative activities have some positive effect on behavioral changes, self-confidence, self esteem, levels of knowledge, and physical activity. Evidence from digital platforms supports Internet-based prevention and treatment programs for anxiety and depression; however, more extensive and rigorous research is warranted to further establish the conditions. Among individual- and family-based interventions, interventions focusing on eating attitudes and behaviors show no impact on body mass index (SMD: -.10; 95% CI: -.45 to .25); Eating Attitude Test (SMD: .01; 95% CI: -.13 to .15); and bulimia (SMD: -.03; 95% CI: -.16 to .10). Exercise is found to be effective in improving self-esteem (SMD: .49; 95% CI: .16 .81) and reducing depression score (SMD: -.66; 95% CI: -1.25 to -.08) with no impact on anxiety scores. Cognitive behavioral therapy compared to waitlist is effective in reducing remission (odds ratio: 7.85; 95% CI: 5.31-11.6). Psychological therapy when compared to antidepressants have comparable effect on remission, dropouts, and depression symptoms. The studies evaluating mental health interventions among adolescents were reported to be very heterogeneous, statistically, in their populations, interventions, and outcomes; hence, meta analysis could not be conducted in most of the included reviews. Future trials should also focus on standardized interventions and outcomes for synthesizing the exiting body of knowledge. There is a need to report differential effects for gender, age groups, socioeconomic status, and geographic settings since the impact of mental health interventions might vary according to various contextual factors. PMID- 27664598 TI - Interventions to Prevent Unintentional Injuries Among Adolescents: A Systematic Review and Meta-Analysis. AB - Globally, every day, ~2,300 children and adolescents succumb to unintentional injuries sustained from motor vehicle collisions, drowning, poisoning, falls, burns, and violence. The rate of deaths due to motor vehicle injuries in adolescents is 10.2 per 100,000 adolescents. We systematically reviewed published evidence to identify interventions to prevent unintentional injuries among adolescents aged 11-19 years. We defined unintentional injuries as a subset of injuries for which there was no evidence of predetermined intent, and the definition included motor vehicle injuries, suffocation, drowning, poisoning, burns, falls, and sports and recreation. Thirty-five studies met study eligibility criteria. The included studies focused on interventions to prevent motor vehicle injuries and sports-related injuries. Results suggest that possession of a graduated driver license (GDL) significantly reduced road accidents by 19% (relative risk [RR]: .81; 95% confidence interval [CI]: .75-.88; n = 5). There was no impact of GDL programs on incidence of injuries (RR: .78; 95% CI: .57-1.06; n = 2), helmet use (RR: 1.0; 95% CI: .98-1.02; n = 3), and seat belt use (RR: .99; 95% CI: .97-1.0; n = 3). Sports-related injury prevention interventions led to reductions in the incidence of injuries (RR: .66; 95% CI: .53-.82; n = 15), incidence of injury per hour of exposure (RR: .63; 95% CI: .47 .86; n = 5), and injuries per number of exposures (RR: .79; 95% CI: .70-.88; n = 4). Subgroup analysis according to the type of interventions suggests that training +/- education and the use of safety equipment had significant impacts on reducing the incidence of injuries. We did not find any study focusing on interventions to prevent suffocation, drowning, poisoning, burns, and falls in the adolescent age group. The existing evidence is mostly from high-income countries, limiting the generalizability of these findings for low- and middle income countries. Studies evaluating these interventions need to be replicated in a low- and middle-income country-context to evaluate effectiveness with standardized outcome measures. PMID- 27664599 TI - Adolescent Health Interventions: Conclusions, Evidence Gaps, and Research Priorities. AB - Adolescent health care is challenging compared to that of children and adults, due to their rapidly evolving physical, intellectual, and emotional development. This paper is the concluding paper for a series of reviews to evaluate the effectiveness of interventions for improving adolescent health and well-being. In this paper, we summarize the evidence evaluated in the previous papers and suggest areas where there is enough existing evidence to recommend implementation and areas where further research is needed to reach consensus. Potentially effective interventions for adolescent health and well-being include interventions for adolescent sexual and reproductive health, micronutrient supplementation, nutrition interventions for pregnant adolescents, interventions to improve vaccine uptake among adolescents, and interventions for substance abuse. Majority of the evidence for improving immunization coverage, substance abuse, mental health, and accidents and injury prevention comes from high-income countries. Future studies should specifically be targeted toward the low- and middle-income countries with long term follow-up and standardized and validated measurement instruments to maximize comparability of results. Assessment of effects by gender and socioeconomic status is also important as there may be differences in the effectiveness of certain interventions. It is also important to recognize ideal delivery platforms that can augment the coverage of proven adolescent health-specific interventions and provide an opportunity to reach hard to-reach and disadvantaged population groups. PMID- 27664597 TI - Interventions for Adolescent Substance Abuse: An Overview of Systematic Reviews. AB - Many unhealthy behaviors often begin during adolescence and represent major public health challenges. Substance abuse has a major impact on individuals, families, and communities, as its effects are cumulative, contributing to costly social, physical, and mental health problems. We conducted an overview of systematic reviews to evaluate the effectiveness of interventions to prevent substance abuse among adolescents. We report findings from a total of 46 systematic reviews focusing on interventions for smoking/tobacco use, alcohol use, drug use, and combined substance abuse. Our overview findings suggest that among smoking/tobacco interventions, school-based prevention programs and family based intensive interventions typically addressing family functioning are effective in reducing smoking. Mass media campaigns are also effective given that these were of reasonable intensity over extensive periods of time. Among interventions for alcohol use, school-based alcohol prevention interventions have been associated with reduced frequency of drinking, while family-based interventions have a small but persistent effect on alcohol misuse among adolescents. For drug abuse, school-based interventions based on a combination of social competence and social influence approaches have shown protective effects against drugs and cannabis use. Among the interventions targeting combined substance abuse, school-based primary prevention programs are effective. Evidence from Internet-based interventions, policy initiatives, and incentives appears to be mixed and needs further research. Future research should focus on evaluating the effectiveness of specific interventions components with standardized intervention and outcome measures. Various delivery platforms, including digital platforms and policy initiative, have the potential to improve substance abuse outcomes among adolescents; however, these require further research. PMID- 27664600 TI - Parathyroid carcinoma in tertiary hyperparathyroidism. AB - Parathyroid carcinoma is a rare disease of unknown etiology. This study presents a case of parathyroid carcinoma in a patient with tertiary hyperparathyroidism. Despite a successful kidney transplantation, the intact parathyroid hormone (iPTH) level of the patient was elevated consistently and could not be controlled by medical therapy. Due to the development of tertiary hyperparathyroidism with bone pain and osteoporosis, subtotal parathyroidectomy was performed 4 months after the kidney transplantation. Histological evaluation revealed that one of four parathyroid lesions was a parathyroid carcinoma, while the others were diffuse hyperplasia. Postoperative laboratory studies indicated a decreased level of iPTH. A positron emission tomography-computed tomography performed 6 months after the operation revealed no evidence of local recurrence or distant metastasis. PMID- 27664601 TI - Kinetics of the incorporation of the main phenolic compounds into the lignan macromolecule during flaxseed development. AB - The main flax lignan, secoisolariciresinol diglucoside, is stored in a macromolecule containing other ester-bound phenolic compounds. In this study, NMR and HPLC-UV analyses were performed on flaxseeds harvested at different developmental stages to identify and quantify the main phenolic compounds produced during seed development. Extraction was carried out with or without alkaline hydrolysis to determine if these molecules accumulate in the lignan macromolecule and/or in a free form. Monolignol glucosides accumulate in a free form up to 9.85mg/g dry matter at the early developmental stages. Hydroxycinnamic acid glucosides and flavonoid accumulate (up to 3.18 and 4.07mg/g dry matter, respectively) in the later developmental stages and are ester-bound in the lignan macromolecule. Secosiolariciresinol diglucoside accumulates (up to 28.65mg/g dry matter) in the later developmental stages in both forms, mainly ester-bound in the lignan macromolecule and slightly in a free form. PMID- 27664602 TI - Effects of chemical and enzymatic modifications on starch-linoleic acid complex formation. AB - This study investigated the complexation yield and physicochemical properties of soluble and insoluble starch complexes with linoleic acid when a beta-amylase treatment was applied to acetylated and debranched potato starch. The degree of acetylation was generally higher in the soluble complexes than in the insoluble ones. The insoluble complexes from the acetylated starch displayed the V-type pattern, whereas, the soluble complexes displayed a mixture of either the A-/V type or the B-/V-type pattern. Acetylation decreased onset and peak melting temperatures for the insoluble complexes, whereas no melting endotherm was observed in the soluble complexes. Acetylation substantially increased the amount of complexed linoleic acid in the insoluble complexes, but had little positive effect on the formation of the soluble complexes. The beta-amylase treatment significantly increased the complexed linoleic content in both soluble and insoluble complexes for the low acetylated starch, but not for the high acetylated starch. PMID- 27664603 TI - Systematic functional analysis and application of a cold-active serine protease from a novel Chryseobacterium sp. AB - Psychrotolerant bacteria isolated from natural and artificially cold environments were screened for synthesis of cold-active protease. The strain IMDY showing the highest protease production at 5 degrees C was selected and phylogenetic analysis revealed that IMDY as novel bacterium with Chryseobacterium soli(T) as its nearest neighbor. Classical optimization enhanced the protease production from 18U/mg to 26U/mg and the enzyme was found to be active at low temperature, activity enhanced by CaCl2, inhibited by PMSF, stable against NaCl, and its activity retained in the presence of surfactants, organic solvents and detergents. On testing, the meat tenderization, myofibril fragmentation, pH, and TBA values were favorable in IMDY-protease treated meat compared to control. SDS profiling and SEM analysis also showed tenderization in meat samples. Hence, this study proposes to consider the cold-active protease from Chryseobacterium sp. IMDY as a pertinent candidate to develop potential applications in food processing industry. PMID- 27664604 TI - Impact of solid state fermentation on nutritional, physical and flavor properties of wheat bran. AB - To improve the nutritional, physical and flavor properties of wheat bran, yeast and lactic acid bacteria (LAB) were used for fermenting wheat bran in solid state. Appearance properties, nutritional properties, microstructure, hydration properties and flavor of raw bran and fermented bran were evaluated. After treatments, water extractable arabinoxylans were 3-4 times higher than in raw bran. Total dietary fiber and soluble dietary fiber increased after solid state fermentation. Over 20% of phytic acid was degraded. Microstructure changes and protein degradation were observed in fermented brans. Water holding capacity and water retention capacity of fermented brans were improved. Results suggest that solid state fermentation is an effective way to improve the properties of wheat brans. PMID- 27664605 TI - Applications of computational chemistry to the study of the antiradical activity of carotenoids: A review. AB - A summary of the various quantum chemical analyses that have been employed to evaluate the free radical scavenger capacity of carotenoid molecules are tabulated in this review and the most important observations are discussed. These molecules are able to interact with reactive oxygen species through singlet oxygen scavenging, electron transfer, hydrogen atom abstraction and radical adduct formation. Most studies employ density functional theory to compare the antiradical capacity of different carotenoids with the ones that are most explored theoretically, such as lycopene and beta-carotene. A significant number of these applications have been directed towards understanding the electron transfer mechanism, and a useful tool called the FEDAM (full-electron donor acceptor map) was developed to better evaluate this mechanism. Important aspects that may affect the radical scavenging capacity of carotenoids, such as synergistic effects and solubility, are sometimes overlooked, and a greater number of such compounds should be explored. PMID- 27664606 TI - Effects of 24-epibrassinolide on enzymatic browning and antioxidant activity of fresh-cut lotus root slices. AB - Fresh-cut lotus root slices were treated with 80nM 24-epibrassinolide (EBR) and then stored at 4 degrees C for 8days to investigate the effects on cut surface browning. The results showed that EBR treatment reduced cut surface browning in lotus root slices and alleviated membrane lipid peroxidation as reflected by low malondialdehyde content and lipoxygenase activity. EBR treatment inhibited the activity of phenylalanine ammonia lyase and polyphenol oxidase, and subsequently decreased phenolics accumulation and soluble quniones formation. The treatment also stimulated the activity of peroxidase, catalase and ascorbate peroxidase and delayed the loss of ascorbic acid, which would help prevent membrane lipid peroxidation, as a consequence, reducing decompartmentation of enzymes and substrates causing enzymatic browning. These results indicate that EBR treatment is a promising attempt to control browning at cut surface of fresh-cut lotus root slices. PMID- 27664607 TI - Binding thermodynamics of synthetic dye Allura Red with bovine serum albumin. AB - The interaction between Allura Red and bovine serum albumin (BSA) was studied in vitro at pH 7.4. The fluorescence quenching was classified as static quenching due to the formation of AR-BSA complex, with binding constant (K) ranging from 3.26+/-0.09 to 8.08+/-0.0610(4)L.mol(-1), at the warfarin binding site of BSA. This complex formation was driven by increasing entropy. Isothermal titration calorimetric measurements also showed an enthalpic contribution. The Allura Red diffusion coefficient determined by the Taylor-Aris technique corroborated these results because it reduced with increasing BSA concentration. Interfacial tension measurements showed that the AR-BSA complex presented surface activity, since interfacial tension of the water-air interface decreased as the colorant concentration increased. This technique also provided a complexation stoichiometry similar to those obtained by fluorimetric experiments. This work contributes to the knowledge of interactions between BSA and azo colorants under physiological conditions. PMID- 27664608 TI - Inhibition of cyclodextrins on alpha-galactosidase. AB - This work successfully investigated the effects of different influential factors and hydrophobic cavities of cyclodextrins (CDs) on alpha-galactosidase (alpha Gal) by detecting alpha-Gal activity. The highest inhibitory concentration of three kinds of CDs (alpha-, beta-, and gamma-CD) on alpha-Gal was 10mM. Moreover, the highest inhibition of alpha-Gal was obtained under the following conditions: reaction time of 90min, temperature of 30 degrees C, and pH 6.0. Compared with other CDs, beta-CD showed more ability to interact with alpha-Gal due to its appropriate cavity geometric dimensions. From circular dichroism and nuclear magnetic resonance it was observed that beta-CD changed the secondary structure of alpha-Gal and formed a hydrogen bond with this enzyme. PMID- 27664609 TI - Monitoring protein glycation by electrospray ionization (ESI) quadrupole time-of flight (Q-TOF) mass spectrometer. AB - In this study electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) mass spectrometry was used to investigate protein glycation. The glycated species of cytochrome C, lysozyme, and beta-casein formed during glycation with d-glucose were identified and monitored in binary systems heated at 70 degrees C under dry and aqueous conditions. Cytochrome C had multiple charges in non-glycated state, primarily changing from +13 to +17 positive charges, whereas beta-casein had charge states up to +30. Upon heating with glucose at 70 degrees C in aqueous state, attachment of one glucose molecule onto proteins was observed in each charge state. However, heating in dry state caused much more glucose attachment, leading to the formation of multiple glycoforms of proteins. By using ESI-QTOF-MS technique, formation of glycated cytochrome C containing up to 12 glucose moieties were observed, while glycated species containing 6 and 8 glucose moieties were observed for lysozyme and beta-casein, respectively in various heating conditions. PMID- 27664610 TI - Physiological development of cagaita (Eugenia dysenterica). AB - It was evaluated the physiological aspects of the cagaita (Eugenia dysenterica) development, from anthesis to ripening. The fruits have been subjected to physical and chemical analysis during the fruit life cycle. The total fruit development comprised 37days. There was a steady increase in the total mass of the fruits and significant increase in transverse and longitudinal diameter, adjusting the double sigmoidal behavior in response to changes in the time. From the 23rd DAA, it was observed the beginning of loss of firmness, increase in total and soluble pectin content and a decrease in starch content. It occurred degradation of total chlorophyll and unmasking of carotenoids from 31st days after anthesis. A decrease in pH and, therefore, increase in acidity, low soluble solids content. The sucrose content was extremely low during the cycle. At the end of development, the respiratory and ethylene production peak was observed, suggesting climacteric behavior. PMID- 27664611 TI - Characterization of the glucansucrase GTF180 W1065 mutant enzymes producing polysaccharides and oligosaccharides with altered linkage composition. AB - Exopolysaccharides produced by lactic acid bacteria are extensively used for food applications. Glucansucrase enzymes of lactic acid bacteria use sucrose to catalyze the synthesis of alpha-glucans with different linkage compositions, size and physico-chemical properties. Crystallographic studies of GTF180-DeltaN show that at the acceptor binding sites +1 and +2, residue W1065 provides stacking interactions to the glucosyl moiety. However, the detailed functional roles of W1065 have not been elucidated. We performed random mutagenesis targeting residue W1065 of GTF180-DeltaN, resulting in the generation of 10 mutant enzymes that were characterized regarding activity and product specificity. Characterization of mutant enzymes showed that residue W1065 is critical for the activity of GTF180-DeltaN. Using sucrose, and sucrose (donor) plus maltose (acceptor) as substrates, the mutant enzymes synthesized polysaccharides and oligosaccharides with changed linkage composition. The stacking interaction of an aromatic residue at position 1065 is essential for polysaccharide synthesis. PMID- 27664613 TI - Effect of post-harvest treatment on bioactive phytochemicals of Thai black rice. AB - Because black rice is rich in antioxidants, appropriate methods of post-harvest treatment are necessary for maintaining these bioactive phytochemicals. Drying methods, storage temperatures, storage duration, and packaging methods affected the contents of some bioactive compounds in the two varieties of Thai black rice used in this research. Sun drying reduces the loss of anthocyanins and gamma oryzanols more than does hot air drying. Glutinous black rice stored as paddy at cool room temperature retains more anthocyanins, gamma-oryzanols, and vitamin E than does paddy stored at room temperature. Nylon/LLDPE pouches containing N2 are the most suitable packaging for preserving the key aroma compound 2-acetyl-1 pyrroline (2AP), total phenolic, and anthocyanin contents of unpolished aromatic black rice. These pouches also retard the formation of some common off-flavor compounds. PMID- 27664612 TI - Salting-out extraction of allicin from garlic (Allium sativum L.) based on ethanol/ammonium sulfate in laboratory and pilot scale. AB - Salting-out extraction (SOE) based on lower molecular organic solvent and inorganic salt was considered as a good substitute for conventional polymers aqueous two-phase extraction (ATPE) used for the extraction of some bioactive compounds from natural plants resources. In this study, the ethanol/ammonium sulfate was screened as the optimal SOE system for the extraction and preliminary purification of allicin from garlic. Response surface methodology (RSM) was developed to optimize the major conditions. The maximum extraction efficiency of 94.17% was obtained at the optimized conditions for routine use: 23% (w/w) ethanol concentration and 24% (w/w) salt concentration, 31g/L loaded sample at 25 degrees C with pH being not adjusted. The extraction efficiency had no obvious decrease after amplification of the extraction. This ethanol/ammonium sulfate SOE is much simpler, cheaper, and effective, which has the potentiality of scale-up production for the extraction and purification of other compounds from plant resources. PMID- 27664614 TI - Changes of phenolic-acids and vitamin E profiles on germinated rough rice (Oryza sativa L.) treated by high hydrostatic pressure. AB - This study was performed to investigate changes in the phenolic acid and vitamin E profiles of germinated rough rice following high hydrostatic pressure treatment (HPT). Rough rice was germinated at 37 degrees C for two days and subjected to 0.1, 10, 30, 50, and 100MPa pressures for 24h. The total phenolic acid content increased from 85.37MUg/g at 0.1MPa to 183.52MUg/g at 100MPa. The highest gallic acid (4.29MUg/g), catechin (9.55MUg/g), p-coumaric acid (8.36MUg/g), ferulic acid (14.99MUg/g), salicylic acid (14.88MUg/g), naringin (6.18MUg/g), trans-cinnamic acid (45.23MUg/g), and kaempferol (40.95MUg/g) contents occurred in the sample treated at 100MPa after germination. The maximum vitamin E content of about 2.56 (BG) and 4.34mg/100g (AG) were achieved at 30MPa. These result suggest that a combination of HPT and germination are efficient method for enhancement of functionality in rough rice, and clarify the influence of HPT conditions on the vitamin E and phenolic acid in germination rough rice. PMID- 27664615 TI - Method for the isolation of citric acid and malic acid in Japanese apricot liqueur for carbon stable isotope analysis. AB - A method for detecting the undeclared addition of acidic ingredients is required to control the authenticity of Japanese apricot liqueur. We developed an analytical procedure that minimizes carbon isotope discrimination for measurement of the delta(13)C values of citric and malic acid isolated from Japanese apricot liqueur. Our results demonstrated that freeze-drying is preferable to nitrogen spray-drying, because it does not significantly affect the delta(13)C values of citric acid and results in smaller isotope discrimination for malic acid. Both 0.1% formic acid and 0.2% phosphoric acid are acceptable HPLC mobile phases for the isolation of citric and malic acid, although the delta(13)C values of malic acid exhibited relatively large variation compared with citric acid following isolation using either mobile phase. The developed procedure allows precise delta(13)C measurements of citric and malic acid isolated from Japanese apricot liqueur. PMID- 27664617 TI - Bioactives-retained non-glutinous noodles from nixtamalized Dent and Flint maize. AB - Nixtamalization is a well-known pre-treatment technique in the tortilla industry. Nixtamalized maize (nixtamal) is known for its modified physicochemical as well as nutritional attributes. In the present study, two types of nixtamalization processes (traditional and ecological) were employed for the development of whole grain-maize-based noodles using Dent and Flint maize genotypes. Results showed that ecological nixtamalization had resulted in better cooking and textural qualities of noodles compared to the one prepared traditionally. Dent maize noodles from traditional and ecological nixtamalization had lower retention of phenolics (40 and 64%, respectively) whereas, Flint maize noodles retained 50 and 66% phenolics, respectively. Dent maize noodles had undergone phenolics loss of 5 6% on cooking while those of Flint maize lost only 2%. Ecological nixtamalization maintained the pH of the cooking liquor within an acidic-neutral range and yielded noodle with higher retention of phenolics whereas, the traditional process negatively affected the antioxidant compounds and their properties. PMID- 27664616 TI - A UHPLC method for the simultaneous analysis of biogenic amines, amino acids and ammonium ions in beer. AB - This paper reports a novel UHPLC method for simultaneously quantifying nine biogenic amines, 21 amino acids, and ammonium ions, in beer. Precision values of standard curves slopes were lower than 3.4% and recovery was between 85% and 106%, indicating the absence of matrix effect. Linear calibration curves were obtained for analyte concentrations between two and four orders of magnitude (R(2)>0.996). Repeatability tests returned mean variations of 3.2% and 0.5% for beer and a standard solution, respectively. Sensitivity ranged between 0.03mg/L and 0.63mg/L for the biogenic amines, and 0.05mg/L and 5.19mg/L for other compounds. Original data on the habitual presence of ethanolamine in beers are presented. The method allows for more samples to be assayed per unit time, it uses less solvent than other techniques and therefore reduces costs and the associated waste. It could be a valuable tool for monitoring the safety and quality of beers. PMID- 27664618 TI - Inhibitory effects of propyl gallate on membrane lipids metabolism and its relation to increasing storability of harvested longan fruit. AB - Effects of propyl gallate on membrane lipids metabolism and its relation to storability of harvested longan fruits were studied. The results showed that the propyl gallate-treated longans maintained lower activities of pericarp phospholipase D (PLD), lipase and lipoxygenase (LOX) than those in control fruits. Such treatments could maintain higher levels of pericarp unsaturated fatty acids (USFAs), higher pericarp indices of unsaturated fatty acids (IUFA), and higher pericarp ratio of unsaturated fatty acids to saturated fatty acids (U/S) than those in control fruits. Furthermore, propyl gallate also delayed color changes of pericarp in the harvested longans. Therefore, the postharvest treatments of longan fruits with propyl gallate for increasing storability of longan fruits might be explained by a decrease in activities of PLD, lipase and LOX, and an the increased unsaturation of fatty acids, which could delay membrane lipids metabolism and maintain cell membrane characteristics. PMID- 27664619 TI - Impact of d-limonene synthase up- or down-regulation on sweet orange fruit and juice odor perception. AB - Citrus fruits are characterized by a complex mixture of volatiles making up their characteristic aromas, being the d-limonene the most abundant one. However, its role on citrus fruit and juice odor is controversial. Transgenic oranges engineered for alterations in the presence or concentration of few related chemical groups enable asking precise questions about their contribution to overall odor, either positive or negative, as perceived by the human nose. Here, either down- or up-regulation of a d-limonene synthase allowed us to infer that a decrease of as much as 51 times in d-limonene and an increase of as much as 3.2 times in linalool in juice were neutral for odor perception while an increase of only 3 times in ethyl esters stimulated the preference of 66% of the judges. The ability to address these questions presents exciting opportunities to understand the basic principles of selection of food. PMID- 27664620 TI - High resolution magic angle spinning NMR spectroscopy reveals that pectoralis muscle dystrophy in chicken is associated with reduced muscle content of anserine and carnosine. AB - Increased incidences of pectoralis muscle dystrophy are observed in commercial chicken products, but the muscle physiological causes for the condition remain to be identified. In the present study a high-resolution magic angle spinning (HR MAS) proton ((1)H) NMR spectroscopic examination of intact pectoralis muscle samples (n=77) were conducted to explore metabolite perturbations associated with the muscle dystrophy condition for the very first time. Both in chicken with an age of 21 and 31days, respectively, pectoralis muscle dystrophy was associated with a significantly lower content of anserine (p=0.034), carnosine (p=0.019) and creatine (p=0.049). These findings must be considered intriguing as they corroborate that characteristic muscle di-peptides composed of beta-alanine and histidine derivatives such as anserine are extremely important in homeostasis of contractile muscles as a results of their role as buffering, anti-oxidative, and anti-glycation capacities. PMID- 27664621 TI - Impact of starch-based emulsions on the antibacterial efficacies of nisin and thymol in cantaloupe juice. AB - The use of antimicrobial compounds to prevent foodborne pathogens from contaminating fresh-cut produce has received broad attentions; however, the applications of these compounds are hindered by their rapid depletion in foods. To prolong their efficacies, the use of delivery systems is essential. In this study, oil-in-water emulsions formed using starch octenyl succinate (starch-OS) were used to stabilize nisin and thymol in cantaloupe juice-containing fluid. Listeria monocytogenes V7 and Salmonella enterica serovar Typhimurium were used as model pathogens to evaluate the antimicrobial activities of nisin and thymol formulations in cantaloupe juice. The results showed that the emulsions had much greater capability to retain nisin and thymol over the storage and displayed much greater effect to inhibit Listeria and Salmonella than non-emulsion, aqueous formulations. Starch-OS based emulsions not only retained nisin and thymol activities separately, but also exhibited their cooperative antibacterial effects. PMID- 27664622 TI - Protein markers for discrimination of meat species in raw beef, pork and poultry and their mixtures. AB - The purpose of this study was to find discrimination markers for four major meat species such as beef, pork, chicken and duck. Myofibrillar and sarcoplasmic proteins isolated from each meat type were analyzed by one-dimensional gel electrophoresis and some proteins were identified through LC-MS/MS analysis. We confirmed that troponin I (TnI), enolase 3, l-lactate dehydrogenase (LDH) and triose-phosphate isomerase (TPI) could be useful markers for discrimination of mammals from poultry due to their different electrophoretic mobility. Tropomyosin 1 and carbonic anhydrase 3 were observed as muscle fiber type-related proteins and these could also be markers to distinguish mammals from poultry. Species specific peptides identified by LC-MS/MS spectra allow the identification of each species regardless of the same protein. Therefore, it is easy to discriminate between mammals and poultry by comparing the electrophoretic mobility of TnI, enolase 3, LDH, TPI and CA3, and each species could be identified through LC MS/MS analysis. PMID- 27664623 TI - Metabolome based volatiles profiling in 13 date palm fruit varieties from Egypt via SPME GC-MS and chemometrics. AB - Dates (Phoenix dactylifera L.) are distributed worldwide as major food complement providing a source of sugars and dietary fiber as well as macro- and micronutrients. Although phytochemical analyses of date fruit non-volatile metabolites have been reported, much less is known about the aroma given off by the fruit, which is critical for dissecting sensory properties and quality traits. Volatile constituents from 13 date varieties grown in Egypt were profiled using SPME-GCMS coupled to multivariate data analysis to explore date fruit aroma composition and investigate potential future uses by food industry. A total of 89 volatiles were identified where lipid-derived volatiles and phenylpropanoid derivatives were the major components of date fruit aroma. Multivariate data analyses revealed that 2,3-butanediol, hexanal, hexanol and cinnamaldehyde contributed the most to classification of different varieties. This study provides the most complete map of volatiles in Egyptian date fruit, with Siwi and Sheshi varieties exhibiting the most distinct aroma among studied date varieties. PMID- 27664624 TI - Multi-class method for the determination of nitroimidazoles, nitrofurans, and chloramphenicol in chicken muscle and egg by dispersive-solid phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry. AB - This study describes the development of a multiresidue method for the efficient identification and quantification of nitroimidazoles, nitrofurans, and chloramphenicol in chicken and egg. After derivatization of nitrofuran metabolites, dispersive-solid phase extraction was used for the extraction of target analytes. An optimization strategy involved the selection of sorbents and extraction solutions for dispersive-solid phase extraction in order to achieve acceptably high recoveries and reduce co-extractives in the final extracts. Analytes were determined by ultra-high performance liquid chromatography-tandem mass spectrometry, in one single injection with a chromatographic run time of 7.5min. Mean recoveries ranged from 86.4% to 116.7% and interday precision was lower than 18%. The limits of quantification were between 0.1 and 0.5MUg/kg, which were satisfactory to support surveillance monitoring. Finally, the method was applied to real samples, and metabolite of furazolidone, metronidazole and its metabolite, dimetridazole and its metabolite were detected in both chicken and egg samples. PMID- 27664625 TI - Determination of acrylamide in dried fruits and edible seeds using QuEChERS extraction and LC separation with MS detection. AB - Acrylamide is a carcinogenic and neurotoxic process contaminant that is generated from food components during heat treatment, while it is absent in raw foodstuffs. Its level in food arouses great concern. A method for acrylamide extraction and determination in dried fruits (dried prunes and raisins) and edible seeds (almonds, hazelnuts, peanuts, pine nuts, pistachios, and walnuts) using a QuEChERS-LC-ESI-MS-Triple Quadrupole approach was set up. Linearity, sensitivity, accuracy, and precision of the method were satisfactory. Dried prunes and peanuts were the only samples appreciably contaminated, 14.7-124.3 and 10.0-42.9MUg/kg, respectively, as a consequence of the drying process. In fact, prunes are dried at 70-80 degrees C for a quite long time (24-36h), while peanuts undergo a roasting process at 160-180 degrees C for 25-30min. The relative standard deviations, accuracy, LOD, and LOQ show that the method provides a reliable approach to acrylamide determination in different matrices. PMID- 27664626 TI - Tea polyphenol epigallocatechin gallate inhibits Escherichia coli by increasing endogenous oxidative stress. AB - The antibacterial effects of tea polyphenol epigallocatechin gallate (EGCG), a common phytochemical with a number of potential health benefits, are well known. However, the mechanism of its bactericidal action remains unclear. Using E. coli as a model organism, it is argued here that H2O2 synthesis by EGCG is not attributed to its inhibitory effects. In contrast, the bactericidal action of EGCG was a result of increased intracellular reactive oxygen species and blunted adaptive oxidative stress response in E. coli due to the co-administration of antioxidant N-acetylcysteine, and not on account of exogenous catalase. Furthermore, we noted a synergistic bactericidal effect for EGCG when combined with paraquat. However, under anaerobic conditions, the inhibitory effect of EGCG was prevented. In conclusion, EGCG caused an increase in endogenous oxidative stress in E. coli, thereby inhibiting its growth, and hence the use of EGCG as a prooxidant is supported by this study. PMID- 27664627 TI - Use of sacrificial anode technology to mitigate non-enzymic Maillard browning. AB - Experiments were performed to examine the effects of Maillard browning induced in the presence of metallic elements. The rate of brown pigment formation was shown to be reduced in model Maillard reactions performed in the presence of electropositive metals. Experiments involved reactions of d-xylose, d-arabinose and d-ribose with glycine, alpha-l- or beta-alanine and l-valine in pH 7.0 phosphate buffer at ca. 100 degrees C. "Browning" measured spectrophotometrically at 420nm was significantly lower (compared with controls) in selected reactions containing elemental Mg, Al, Mn and Sn particles. It was hypothesized that the metals acted in sacrificial anode redox fashion to reduce or eliminate dehydroreductones believed to be key Maillard intermediates ultimately leading to less browning. PMID- 27664628 TI - Influence of cooking conditions on organoleptic and health-related properties of artichokes, green beans, broccoli and carrots. AB - Colour, pigments, total phenolic content and antioxidant activity were investigated in artichokes, green beans, broccoli and carrots cooked under different conditions. Domestic induction hobs with temperature control were used to evaluate the effect of boiling, sous-vide cooking and water immersion cooking at temperatures below 100 degrees C on the properties of each vegetable. Sous vide cooking preserved chlorophyll, carotenoids, phenolic content and antioxidant activity to a greater extent than boiling for all of the vegetables tested and retained colour better, as determined by a(*). A reduction of only 10-15 degrees C in the cooking temperature was enough to improve the properties of the samples cooked by water immersion, except for green beans. Artichokes and carrots suffered pronounced losses of antioxidant activity during boiling (17.0 and 9.2% retention, respectively), but the stability of this parameter significantly increased with sous-vide cooking (84.9 and 55.3% retention, respectively). PMID- 27664629 TI - The cadmium and lead content of the grain produced by leading Chinese rice cultivars. AB - The cadmium (Cd) and lead (Pb) content in both white and wholemeal flour milled from 110 leading rice cultivars was assessed. The white flour Cd content ranged from <0.0025 to 0.2530mg/kg (geometric mean (GM)=0.0150mg/kg), while its Pb content ranged from <0.0250 to 0.3830mg/kg (GM=0.0210mg/kg). The indica types took up higher amounts of Cd and Pb than did the japonica types. Although the heavy metal content of wholemeal flour tended to higher than that of white flour, nevertheless 84.5% (Cd) and 95.4% (Pb) of the entries were compliant with the national maximum allowable concentration of 0.2000mg/kg of each contaminant. An analysis of the Cd content in the white flour of three indica type cultivars grown in two consecutive years at two locations indicated that Cd content may be significantly affected by the conditions prevailing in the growing season. PMID- 27664630 TI - QuEChERS-based extraction with dispersive solid phase extraction clean-up using PSA and ZrO2-based sorbents for determination of pesticides in bovine milk samples by HPLC-DAD. AB - In this study, a quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction technique was adapted to develop a simple sample treatment for multi residue pesticide analysis in milk samples. The proposed method is based on liquid-liquid partitioning with acetonitrile followed by dispersive solid phase extraction clean-up using primary secondary amine along with zirconia-coated silica particles for extract purification. Identification and quantification of 30 pesticides was conducted via high performance liquid chromatography with diode array detection (HPLC-DAD). Recoveries were from 70 to 100% for the vast majority of the analytes, with relative standard deviations less than 20% being observed. HPLC-DAD provided suitable linearity, precision and accuracy. For 28 of 30 analytes in the study method limit of quantification values (mLOQs) comply with the most recent European Union guidelines for the maximum residue levels (MRLs) in milk. Negligible matrix effect was observed due to efficient extract clean-up with ZrO2-based sorbents. PMID- 27664631 TI - Understanding leaf membrane protein extraction to develop a food-grade process. AB - Leaf membrane proteins are an underutilised protein fraction for food applications. Proteins from leaves can contribute to a more complete use of resources and help to meet the increasing protein demand. Leaf protein extraction and purification is applied by other disciplines, such as proteomics. Therefore, this study analysed proteomic extraction methods for membrane proteins as an inspiration for a food-grade alternative process. Sugar beet leaves were extracted with two proteomic protocols: solvent extraction and Triton X-114 phase partitioning method. Extraction steps contributed to protein purity and/or to selective fractionation, enabling the purification of specific proteins. It was observed that membrane proteins distributed among different solvents, buffers and solutions used due to their physicochemical heterogeneity. This heterogeneity does not allow a total membrane protein extraction by a unique method or even combinations of processing steps, but it enables the creation of different fractions with different physicochemical properties useful for food applications. PMID- 27664632 TI - Identification of predominant aroma components of raw, dry roasted and oil roasted almonds. AB - Volatile components of raw, dry roasted and oil roasted almonds were isolated by solvent extraction/solvent-assisted flavor evaporation and predominant aroma compounds identified by gas chromatography-olfactometry (GCO) and aroma extract dilutions analysis (AEDA). Selected odorants were quantitated by GC-mass spectrometry and odor-activity values (OAVs) determined. Results of AEDA indicated that 1-octen-3-one and acetic acid were important aroma compounds in raw almonds. Those predominant in dry roasted almonds were methional, 2- and 3 methylbutanal, 2-acetyl-1-pyrroline and 2,3-pentanedione; whereas, in oil roasted almonds 4-hydroxy-2,5-dimethyl-3(2H)-furanone, 2,3-pentanedione, methional and 2 acetyl-1-pyrroline were the predominant aroma compounds. Overall, oil roasted almonds contained a greater number and higher abundance of aroma compounds than either raw or dry roasted almonds. The results of this study demonstrate the importance of lipid-derived volatile compounds in raw almond aroma. Meanwhile, in dry and oil roasted almonds, the predominant aroma compounds were derived via the Maillard reaction, lipid degradation/oxidation and sugar degradation. PMID- 27664633 TI - Rare earth elements and (87)Sr/(86)Sr isotopic characterization of Indian Basmati rice as potential tool for its geographical authenticity. AB - The increasing demand for premium priced Indian Basmati rice (Oryza sativa) in world commodity market causing fraudulent activities like adulteration, mislabelling. In order to develop authentication method for Indian Basmati rice, (87)Sr/(86)Sr ratios and REEs composition of Basmati rice, soil and water samples were determined and evaluated their ability as geographical tracer in the present study. In addition, the possible source of Sr in rice plant has also been examined. Basmati rice samples (n=82) showed (87)Sr/(86)Sr ratios in the range 0.71143-0.73448 and concentrations of 10 REEs (La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Er, Yb) in ppb levels. Statistical analysis showed strong correlation between (87)Sr/(86)Sr ratios of rice, silicate and carbonate fractions of soil. Good correlation and closeness of (87)Sr/(86)Sr of rice with water indicate its uptake in rice from water. Rice grown in southern Uttar Pradesh contains higher (87)Sr/(86)Sr compared to other region of Indo-Gangetic Plain due to higher (87)Sr/(86)Sr of the Ganga compared to other rivers. (87)Sr/(86)Sr ratios can be used as a tracer for differentiating Indian Basmati rice from the other country originated rice samples. PMID- 27664634 TI - Nutritional value of duckweeds (Lemnaceae) as human food. AB - Duckweeds have been consumed as human food since long. Species of the duckweed genera, Spirodela, Landoltia, Lemna, Wolffiella and Wolffia were analysed for protein, fat, and starch contents as well as their amino acid and fatty acid distribution. Protein content spanned from 20% to 35%, fat from 4% to 7%, and starch from 4% to 10% per dry weight. Interestingly, the amino acid distributions are close to the WHO recommendations, having e.g. 4.8% Lys, 2.7% Met+Cys, and 7.7% Phe+Tyr. The content of polyunsaturated fatty acids was between 48 and 71% and the high content of n3 fatty acids resulted in a favourable n6/n3 ratio of 0.5 or less. The phytosterol content in the fastest growing angiosperm, W. microscopica, was 50mgg(-1) lipid. However, the content of trace elements can be adjusted by cultivation conditions. Accordingly, W. hyalina and W. microscopica are recommended for human nutrition. PMID- 27664635 TI - Synchronous front-face fluorescence spectroscopy for authentication of the adulteration of edible vegetable oil with refined used frying oil. AB - Synchronous front-face fluorescence spectroscopy has been developed for the discrimination of used frying oil (UFO) from edible vegetable oil (EVO), the estimation of the using time of UFO, and the determination of the adulteration of EVO with UFO. Both the heating time of laboratory prepared UFO and the adulteration of EVO with UFO could be determined by partial least squares regression (PLSR). To simulate the EVO adulteration with UFO, for each kind of oil, fifty adulterated samples at the adulterant amounts range of 1-50% were prepared. PLSR was then adopted to build the model and both full (leave-one-out) cross-validation and external validation were performed to evaluate the predictive ability. Under the optimum condition, the plots of observed versus predicted values exhibited high linearity (R(2)>0.96). The root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP) were both lower than 3%. PMID- 27664636 TI - Spices in the management of diabetes mellitus. AB - Diabetes mellitus (DM) remains a major health care problem worldwide both in developing and developed countries. Many factors, including age, obesity, sex, and diet, are involved in the etiology of DM. Nowadays, drug and dietetic therapies are the two major approaches used for prevention and control of DM. Compared to drug therapy, a resurgence of interest in using diet to manage and treat DM has emerged in recent years. Conventional dietary methods to treat DM include the use of culinary herbs and/or spices. Spices have long been known for their antioxidant, anti-inflammatory, and anti-diabetic properties. This review explores the anti-diabetic properties of commonly used spices, such as cinnamon, ginger, turmeric, and cumin, and the use of these spices for prevention and management of diabetes and associated complications. PMID- 27664637 TI - First identification of three p-menthane lactones and their potential precursor, menthofuran, in red wines. AB - The p-menthane lactones constitute a family of powerful odorants, including the isomers of mintlactone and menthofurolactone that occur naturally in peppermint oil, known for their potent, mint-like olfactory properties. These lactones are closely related to the monoterpene-limonene secondary biotransformation and menthofuran has been identified as their common precursor in Mentha species. Using targeted GC-olfactometry and GC-MS analyses, together with quantification methods, we were able to demonstrate, for the first time, the presence of the diastereoisomers of these p-menthane lactones, as well as their common precursor, menthofuran, in red wines. In addition, we linked the presence of those lactones to interesting odorant zones, reminiscent of mint, detected in the studied wine. Although these p-menthane lactones may contribute individually to mint and coconut odors, sensory studies suggested for the first time that their combination at the levels found in the red wine studied resulted in a significant accentuation of freshness and mint notes. PMID- 27664638 TI - Pyrethroid residue determination in organic and conventional vegetables using liquid-solid extraction coupled with magnetic solid phase extraction based on polystyrene-coated magnetic nanoparticles. AB - A detection method using polystyrene-coated magnetic nanoparticles based extraction technique coupled to HPLC was developed for trace amount of pyrethroids residue detection in vegetable matrixes. The recoveries for five kinds of commonly used pyrethroids were in the range of 91.6%-116.2%. The sensitivity and precision of the method were satisfactory with the limits of detection and limits of quantification in the range of 0.0200-0.0392ngg(-1) and 0.072-0.128ngg(-1), respectively. The intra-day and inter-day relative standard deviations for the recoveries of the analytes were lower than 6.8% and 10.7%, respectively. The nanoparticles can be washed and recycled after use. The results indicate that the developed method was efficient, fast, economical and environmentally friendly. The method was successfully applied to detect the pyrethroids residue in ten pairs of commonly consumed organic and conventional fresh vegetables in Singapore. Pyrethroids residue was detected in four kinds of conventional vegetables and one kind of organic vegetable. PMID- 27664639 TI - Mass-based metabolomic analysis of soybean sprouts during germination. AB - We investigated the metabolite profile of soybean sprouts at 0, 1, 2, 3, and 4days after germination using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-MS (LC-MS) to understand the relationship between germination and nutritional quality. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and sprout samples were separated successfully using their PLS-DA scores. Fifty-eight metabolites, including macromolecular derivatives related to energy production, amino acids, myo-inositol metabolites, phytosterols, antioxidants, isoflavones, and soyasaponins, contributed to the separation. Amino acids, myo-inositol metabolites, isoflavone aglycones, B soyasaponins, antioxidants, and phytosterols, associated with health benefits and/or taste quality, increased with germination time while isoflavone glycosides and DDMP soyasaponins decreased. Based on these metabolites, the metabolomic pathway associated with energy production in soybean sprouts is suggested. Our data suggest that sprouting is a useful processing step to improve soybean nutritional quality, and metabolomic analysis is useful in understanding nutritional change during sprouting. PMID- 27664640 TI - Magnetic solid-phase extraction based on graphene oxide for the determination of lignans in sesame oil. AB - Graphene oxide was fabricated by a simple method and applied to magnetic solid phase extraction. In a pretreatment procedure before the sesamol, sesamin and sesamolin in sesame oil were detected by high performance liquid chromatography. Several parameters affecting the extraction efficiency were investigated, including the type and volume of desorption solvent, desorption time and the amount of sorbent. Under the optimized conditions, the detection limits of sesamol, sesamin, and sesamolin were 0.05MUg/g, 0.02MUg/g, and 0.02MUg/g, respectively. The limits of quantification were all 0.2MUg/g. The average recoveries of sesamol, sesamin, and sesamolin were 84.55%, 85.47%, 86.83%, respectively and their relative standard deviations were 1.23%, 1.33%, and 0.84%, respectively. PMID- 27664641 TI - Electroanalytical tools for antioxidant evaluation of red fruits dry extracts. AB - Red fruits are rich sources of antioxidant compounds with recognized health benefits. Since they are perishable, dried extracts emerge as more durable products and their quality control must include antioxidant capacity assays. In this study, the redox behavior of commercial dried products obtained from camu camu, acai, acerola and cranberry red fruits was evaluated by electroanalytical approaches. The antioxidant potential was determined by 2,2-diphenyl-1 picrylhydrazyl free radical assay and the electrochemical index concept. The total phenol content was estimated by using a laccase based biosensor. A significant correlation was found between all methods and literature data. The voltammetric profile (cyclic, differential and square wave) obtained for each type of dried extract showed distinguishable features that were correlated with their main major markers, being also useful for identification purposes. The electrochemical methods were cheaper and more practical for evaluation of antioxidant properties and total phenol content in dried powders obtained from different red fruits. PMID- 27664642 TI - Enrichment of caffeic acid in peanut sprouts and evaluation of its in vitro effectiveness against oxidative stress-induced erythrocyte hemolysis. AB - The profile of caffeic acid in tissues of peanut sprouts and its antioxidant activity in erythrocyte-based assays were investigated. Caffeic acid was found to accumulate in the epicotyl-plumule (reached 2097.13+/-96MUg/g DW on day 10 after peanut germination). It was purified by semipreparative high-performance liquid chromatography. The purified caffeic acid showed noticeable protective effects on human erythrocytes against 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) induced hemolysis. It also contributed to maintenance of normal morphological features and inhibited malondialdehyde formation and the lactate dehydrogenase release in erythrocytes under oxidative stress. Further analysis revealed that caffeic acid effectively inhibited AAPH-induced free-radical production and maintained the normal metabolism of the erythrocytic redox system, including superoxide dismutase, glutathione peroxidase, and glutathione. Our work showed that caffeic acid, which is greatly enriched in peanut sprout, can effectively protect erythrocytes from oxidative damage. These results provide valuable information for the use of peanut sprouts as a functional food. PMID- 27664643 TI - Changes in the antigenicity and allergenicity of ovalbumin in chicken egg white by N-acetylglucosaminidase. AB - Ovalbumin (OVA), an (hen) egg allergen, is one of the most abundant glycoprotein allergens associated with IgE-mediated hypersensitivity through the T-helper type 2 immune response. The effect of deglycosylation of the N-terminal glycan in OVA on allergenicity and antigenicity after N-acetylglucosaminidase treatment was studied. N-acetylglucosaminidase-treated OVA (N-OVA) evaluated using an enzyme linked immunosorbent assay, respectively. N-OVA significantly (p<0.05) OVA specific IgE and histamine levels. In addition, N-OVA decreased the antigenicity of OVA 1000-fold. These results suggest that the degree of allergenicity and antigenicity reduced with deglycosylation of N-terminal glycan in OVA. PMID- 27664644 TI - Development of HPLC-ELSD method for determination of maltodextrin in raw milk. AB - An analytical method was developed and validated for the determination of maltodextrin in raw milk, using high-performance liquid chromatography with evaporative light scattering detection. Maltodextrin content was evaluated in adulterated raw milk using a Supelcosil LC-NH2 (25cm*4.6mm) column and isocratic elution (68% of acetonitrile). Validation parameters exhibited adequate linearity, with relative standard deviation values between 0.74 and 2.16% (n=10) for repeatability and 0.11-19.39% (n=5) for intermediate precision. Limits of detection and quantification were 0.78 and 1.56mg.mL(-1), respectively, and recovery rates were between 91 and 93% for three levels. The application of this method shows that maltodextrin concentrations found in adulterated samples are lower than expected, which may be related to the quality of the commercial maltodextrin used. The method proposed proved to be simple and appropriate for the determination of maltodextrin in raw milk, with detection down to adulteration levels of 1%. PMID- 27664645 TI - Determination of 2-alkylcyclobutanones in ultraviolet light-irradiated fatty acids, triglycerides, corn oil, and pork samples: Identifying a new source of 2 alkylcyclobutanones. AB - Previous studies have established that 2-alkylcyclobutanones (2-ACBs) are unique radiolytic products in lipid-containing foods that could only be formed through exposure to ionizing radiation, but not by any other means of physical/heat treatment methods. Therefore, 2-ACBs are currently the marker molecules required by the European Committee for Standardization to be used to identify foods irradiated with ionizing irradiation. Using a spectrum of state-of-the-art analytical instruments, we present in this study for the first time that the generation of 2-ACBs was also possible when fatty acids and triglycerides are exposed to a non-ionizing, short-wavelength ultraviolet (UV-C) light source. An irradiation dosage-dependent formation of 2-ACBs was also observed in UV-C irradiated fatty acids, triglycerides, corn oil, and pork samples. With UV-C irradiation becoming an increasingly common food treatment procedure, it is anticipated that the results from this study will alert food scientists and regulatory officials to a potential new source for 2-ACBs. PMID- 27664646 TI - Application of mesoporous silica materials for the immobilization of polyphenol oxidase. AB - The ability of a number of mesoporous silica materials (SBA-15, SBA-3, and MCM 48) to immobilize polyphenol oxidase (PPO) at different pH has been tested. Pore size and volume are the structural characteristics with higher influence on the PPO immobilization. Mesoropous material SBA-15 adsorbs a larger quantity of PPO at pH 4.00 and offers an inhibition of enzymatic activity close the 50% in apple extracts. PMID- 27664647 TI - Polyphenolic composition and antioxidant activity of acai (Euterpe oleracea Mart.) from Colombia. AB - Berries of Colombian Euterpe oleracea Mart. were analyzed for total phenolic content (TPC), anthocyanin (ACN) content, and antioxidant activity. Additionally, reversed-phase ultra-high performance liquid chromatography with photodiode array detection (RP-UHPLC-PDA) and heated electrospray ionization (HESI) multistage mass spectrometry (MS(n)) were used to determine the composition of phenolic compounds. Anthocyanin content was 0.57+/-0.39mg cyanidin-3-glucoside/g fresh weight (FW) and TPC was 6.07+/-2.17mg gallic acid equivalent (GAE)/g FW. The ABTS radical scavenging activity was 3.1+/-1.3MUmol Trolox equivalents (TE)/100g FW, whereas the DPPH value was 2693.1+/-332.8MUmol TE/100g FW. Overall, results show that Colombian acai has a more diverse polyphenolic profile and higher antioxidant activity than Brazilian acai. This information could be useful in authentification procedures to differentiate Brazilian acai from Colombian acai when used as an alternative for the supply of this fruit during the time of shortage in Brazil. PMID- 27664648 TI - Spectroscopy reveals that ethyl esters interact with proteins in wine. AB - Impairment of wine aroma after vinification is frequently associated to bentonite treatments and this can be the result of protein removal, as recently demonstrated for ethyl esters. To evaluate the existence of an interaction between wine proteins and ethyl esters, the effects induced by these fermentative aroma compounds on the secondary structure and stability of VVTL1, a Thaumatin like protein purified from wine, was analyzed by Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The secondary structure of wine VVTL1 was not strongly affected by the presence of selected ethyl esters. In contrast, VVTL1 stability was slightly increased by the addition of ethyl-octanoate, -decanoate and -dodecanoate, but decreased by ethyl-hexanoate. This indicates the existence of an interaction between VVTL1 and at least some aroma compounds produced during fermentation. The data suggest that proteins removal from wine by bentonite can result in indirect removal of at least some aroma compounds associated with them. PMID- 27664649 TI - Geoclimatic, morphological, and temporal effects on Lebanese olive oils composition and classification: A (1)H NMR metabolomic study. AB - Two hundred and thirty-four Lebanese olive samples were collected from different regions and the corresponding oils were analysed by (1)H NMR spectroscopy. The variables obtained, related to fatty acids and minor components, were used as inputs in univariate and multivariate analyses aiming to characterize and classify the oils according to geographical, morphological, and temporal factors. Samples were sorted according to the colour, size, and shape of olives, which allowed statistically significant classifications to be achieved. A sequential strategy was developed to discriminate among samples from different altitudes and latitudes. Following this strategy, obvious trends and classifications were obtained at subregional level. Furthermore, the shift in the harvest date within a range of three weeks was considered and its effect on the classification models was investigated. Likewise, the harvest year effect was evaluated; the precipitation level in April and May had a significant impact on the characteristics of the oils. PMID- 27664651 TI - Chemical, mechanical and sensory monitoring of hot air- and infrared-roasted hazelnuts (Corylus avellana L.) during nine months of storage. AB - Roasted hazelnuts can be consumed as whole nuts, or as an ingredient in the confectionary and bakery industries and are highly appreciated for their typical taste, aroma and crunchy texture. In this work, two hazelnut types (TGT, Ordu) from two harvests were roasted using two different systems (hot air, infrared) at different time/temperature combinations, and the evolution of oxidative stability, the total phenolic content (TPC), the antioxidant capacity, the mechanical and acoustic properties and the sensory perception were determined during storage. The results showed that the oxidative stability was increased by roasting hazelnuts at 120 degrees C for 40min with hot air system. Similar overall trends were not found for the TPC, the antioxidant capacity and the mechanical-acoustic properties. However, for the maintenance of high antioxidant activity, a storage time of 6months at 4 degrees C is recommended. The two roasting systems gave hazelnuts with significant sensory differences only at high roasting temperature. PMID- 27664650 TI - Evaluation of volatile compounds from Chinese dwarf cherry (Cerasus humilis (Bge.) Sok.) germplasms by headspace solid-phase microextraction and gas chromatography-mass spectrometry. AB - The types and amounts of volatiles in denucleated fruit of 30 Chinese dwarf cherry germplasms were determined by headspace solid-phase microextraction and gas chromatography-mass spectrometry to assess the genotypic variation. Eighty five volatiles were identified; hexyl acetate, 4-penten-1-yl acetate, prenyl acetate, (Z)-pent-2-enyl hexanoate, geranyl acetate, n-butyl acetate, (3Z)-3,7 dimethylocta-1,3,6-triene, geraniol, pent-2-enyl butanoate, ethyl caprylate, butyl hexanoate, and linalool were the main volatiles. The type and content of volatile varied with genotype. Red fruits had the most abundant aroma and vinicolor fruits exhibited the least. Principal component analysis clustered the 30 Chinese dwarf cherry germplasms into four groups: (1) 2 germplasms (NM2 and HN3) had high ester content, (2) 24 germplasms (BJ1-BJ6, HB1, HB2, HN1, HN2, NM1, NM3, SX1, SX2, SX4-SX6, SX8-SX10, SX12, SX13, SX15, and SX16) contained mainly esters, lactones, and terpenes, (3) 2 germplasms (SX11 and SX14) had high ester and lactone content, and (4) 2 germplasms (SX3 and SX7) had high ester and terpene content. PMID- 27664652 TI - Influence of juice processing factors on quality of black chokeberry pomace as a future resource for colour extraction. AB - Aronia melanocarpa berries are a rich source of anthocyanins and its pomace, a by product of juice processing, could be efficiently used for extraction of natural colours for the food industry. This study evaluated the influence blanching, freezing, maceration temperatures (2 degrees C, 50 degrees C) and enzyme treatments before juice pressing on the yield and anthocyanin composition of both juice and pomace. Total anthocyanin levels in pomace were affected mostly by enzyme treatment followed by maceration temperature. The pre-heating of the mash prior to processing increased juice yield and retention of anthocyanins in the pomace. Cold maceration of frozen berries without enzyme addition gave the highest concentrations of anthocyanins in the pomace, and both cold and hot maceration of fresh unblanched berries with enzyme the lowest. The results support future exploitation of natural colours from pomace side streams of Aronia, thus increasing competitiveness of Aronia berry production. PMID- 27664653 TI - Sudan dyes in adulterated saffron (Crocus sativus L.): Identification and quantification by (1)H NMR. AB - Saffron, the dried red stigmas of Crocus sativus L., is considered as one of the most expensive spices worldwide, and as such, it is prone to adulteration. This study introduces an NMR-based approach to identify and determine the adulteration of saffron with Sudan I-IV dyes. A complete (1)H and (13)C resonance assignment for Sudan I-IV, achieved by two-dimensional homonuclear and heteronuclear NMR experiments, is reported for the first time. Specific different proton signals for the identification of each Sudan dye in adulterated saffron can be utilised for quantitative (1)H NMR (qHNMR), a well-established method for quantitative analysis. The quantification of Sudan III, as a paradigm, was performed in varying levels (0.14-7.1g/kg) by considering the NMR signal occurring at 8.064ppm. The high linearity, accuracy and rapidity of investigation enable high resolution (1)H NMR spectroscopy to be used for evaluation of saffron adulteration with Sudan dyes. PMID- 27664654 TI - Mineral composition of pulp and production of the yellow passion fruit with organic and conventional fertilizers. AB - The use of organic foods has been increased in the world. Organic fertilizers, like cattle manure, have emerged as an important component of the organic system production. The production, mass, size, and mineral composition of passion fruit pulp were evaluated when treated with a mineral fertilizer (control) (MIN) or cattle manure at a single dose equivalent to potassium fertilizer (ORG) or double dose (2*ORG). The production and the numbers of fruits of plants treated with MIN and 2*ORG was higher than with ORG. The level of nitrogen (N), phosphorus (P), zinc (Zn), iron (Fe), and copper (Cu) in the fruit pulp was similar with all three fertilizers, but the calcium (Ca) and magnesium (Mg) was higher with ORG and 2*ORG. The number and weight of the fruits of passion fruit treated with 2*ORG were similar to those with MIN fertilizer, but they contained more Ca and Mg. PMID- 27664655 TI - Melatonin and derived l-tryptophan metabolites produced during alcoholic fermentation by different wine yeast strains. AB - Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway. This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC-HRMS system (Qexactive). Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation. PMID- 27664656 TI - Isotopic ratio analysis of cattle tail hair: A potential tool in building the database for cow milk geographical traceability. AB - The potential for the isotopic ratio analysis of cattle tail hair in determining the geographical origin of raw cow milk in Peninsular Malaysia had been investigated in this research using exploratory visualization. A significant positive correlation (p<0.0001) (n=54) was noticed between delta(13)C and delta(15)N in milk with that of hair which indicated that these matrices could be used in tracing the geographical origin of animal produce and tissues, and there is a possibility that hair could be used as a substitute in building the database for the geographical traceability of milk. It was also observed that both hair and milk isotopic ratio correlations exhibited separation between the northern and southern regions. The accuracy of using isotopic ratio in determining geographical discrimination had been clearly demonstrated when several commercial milk samples from the same regions under the study were correctly assigned to the appropriate geographical clusters. PMID- 27664657 TI - Characterization and geographical discrimination of commercial Citrus spp. honeys produced in different Mediterranean countries based on minerals, volatile compounds and physicochemical parameters, using chemometrics. AB - The objective of the present study was: i) to characterize Mediterranean citrus honeys based on conventional physicochemical parameter values, volatile compounds, and mineral content ii) to investigate the potential of above parameters to differentiate citrus honeys according to geographical origin using chemometrics. Thus, 37 citrus honey samples were collected during harvesting periods 2013 and 2014 from Greece, Egypt, Morocco, and Spain. Conventional physicochemical and CIELAB colour parameters were determined using official methods of analysis and the Commission Internationale de l' Eclairage recommendations, respectively. Minerals were determined using ICP-OES and volatiles using SPME-GC/MS. Results showed that honey samples analyzed, met the standard quality criteria set by the EU and were successfully classified according to geographical origin. Correct classification rates were 97.3% using 8 physicochemical parameter values, 86.5% using 15 volatile compound data and 83.8% using 13 minerals. PMID- 27664658 TI - Determination of nickel in hydrogenated fats and selected chocolate bars in Czech Republic. AB - Nickel is a metal that can be present in products containing hardened edible oils, possibly as leftover catalyst from the vegetable oil hardening process. Nickel may cause toxic effects including the promotion of cancer and contact allergy. In this work, nickel content was determined in hydrogenated vegetable fats and confectionery products, made with these fats, available on the Czech market using newly developed method combining microwave digestion and graphite furnace AAS. While concentrations of 0.086+/-0.014mg.kg(-1) or less were found in hydrogenated vegetable fats, the Ni content in confectionery products was significantly higher, varying between 0.742+/-0.066 and 3.141+/-0.217mg.kg(-1). Based on an average consumer basket, daily intake of nickel from vegetable fats is at least twice as low as intake from confectionery products. Based on results, the levels of nickel in neither vegetable fats nor confectionery products, do not represent a significant health risk. PMID- 27664659 TI - An efficient method for decoloration of polysaccharides from the sprouts of Toona sinensis (A. Juss.) Roem by anion exchange macroporous resins. AB - An efficient decoloration method for polysaccharides from the sprouts of Toona sinensis (A. Juss.) Roem (PSTS) by anion exchange macroporous resins (AEMR) was investigated in the present paper. The results suggested that D941 resin offered better decoloration efficiency than other tested resins. Based on single-factor experiments, the optimal decoloration parameters of D941 resin were obtained as follows: temperature of 45 degrees C, sample initial concentration of 30mg/ml, pH value of 8.5, static decoloration time of 90min, dynamic decoloration processing volume of 5.5BV with the flow rate of 2BV/h. Decoloration ratio, PSTS recovery ratio and selectivity coefficient were 91.94+/-1.23%, 90.05+/-2.35% and 10.92+/ 0.63, respectively. Most of pigment impurities were successfully removed from PSTS solutions after treated by D941 resin, and there was no significant difference in carbohydrate concentration, characteristic groups and molecular weight. Compared with H2O2 oxidation and activated carbon adsorption, this developed method is superior. PMID- 27664660 TI - Fluorescence spectroscopy and principal component analysis of soy protein hydrolysate fractions and the potential to assess their antioxidant capacity characteristics. AB - The potential of intrinsic fluorescence and principal component analysis (PCA) to characterize the antioxidant capacity of soy protein hydrolysates (SPH) during sequential ultrafiltration (UF) and nanofiltration (NF) was evaluated. SPH was obtained by enzymatic hydrolysis of soy protein isolate. Antioxidant capacity was measured by Oxygen Radical Absorbance Capacity (ORAC) and Folin Ciocalteau Reagent (FCR) assays together with fluorescence excitation-emission matrices (EEM). PCA of the fluorescence EEMs revealed two principal components (PC1 tryptophan, PC2-tyrosine) that captured significant variance in the fluorescence spectra. Regression models between antioxidant capacity and PC1 and PC2 displayed strong linear correlations for NF fractions and a weak linear correlation for UF fractions. Clustering of UF and NF fractions according to ORACFPCA and FCRFPCA was observed. The ability of this method to extract information on contributions by tryptophan and tyrosine amino acid residues to the antioxidant capacity of SPH fractions was demonstrated. PMID- 27664661 TI - Protein breakdown and release of beta-casomorphins during in vitro gastro intestinal digestion of sterilised model systems of liquid infant formula. AB - Protein modifications occurring during sterilisation of infant formulas can affect protein digestibility and release of bioactive peptides. The effect of glycation and cross-linking on protein breakdown and release of beta-casomorphins was evaluated during in vitro gastro-intestinal digestion (GID) of six sterilised model systems of infant formula. Protein degradation during in vitro GID was evaluated by SDS-PAGE and by measuring the nitrogen content of ultrafiltration (3kDa) permeates before and after in vitro GID of model IFs. Glycation strongly hindered protein breakdown, whereas cross-linking resulting from beta-elimination reactions had a negligible effect. Only beta-casomorphin 7 (beta-CM7) was detected (0.187-0.858mgL(-1)) at the end of the intestinal digestion in all untreated IF model systems. The level of beta-CM7 in the sterilised model systems prepared without addition of sugars ranged from 0.256 to 0.655mgL(-1). The release of this peptide during GID was hindered by protein glycation. PMID- 27664662 TI - Phenolics, antioxidant capacity and bioaccessibility of chicory varieties (Cichorium spp.) grown in Turkey. AB - In this study, the changes in phenolics, anthocyanin, antioxidant capacity, and bioaccessibility of chicory varieties (Cichorium spp.) in Turkey were investigated. A total of 19 phenolic standards were screened in the chicory varieties studied and the most abundant compounds in the samples, extracted with methanol, were phenolic acids, syringic (2.54mg/kg) and trans-ferulic acid (1.85mg/kg), whilst (+)-catechin was the major flavanol. The highest flavanol content using either methanol or ethanol was determined in the green chicory samples (0.62mg/kg). The red chicory variety had higher anthocyanin (12.80mg/kg), and contained more phenolics, extractable (8855.50mg GAE/100g) and hydrolysable (7005.51mg GAE/100g), than the other varieties. Also, the antioxidant capacities in this variety, as measured using the CUPRAC assay (570.54 and 425.14MUmol Trolox/g dw, respectively), had a wider range of difference than was found in the other assays used. Total phenolics were more bioaccessible from the white chicory variety (61.48%). However, the bioaccessibility of antioxidants was higher in the green chicory variety. PMID- 27664663 TI - Varietal classification and antioxidant activity prediction of Osmanthus fragrans Lour. flowers using UPLC-PDA/QTOF-MS and multivariable analysis. AB - This study was aimed to classify the varieties and predict the antioxidant activity of Osmanthus fragrans flowers by UPLC-PDA/QTOF-MS and multivariable analysis. The PLS-DA model successfully classified the four varieties based on both the 21 identified compounds and the effective compounds. For the antioxidant activity prediction, PLS performed well to predict the antioxidant activity of O. fragrans flowers. Furthermore, acteoside, suspensaside A, ligustroside, forsythoside A, phillygenin and caffeic acid were selected as effective compounds by UVE-SPA for prediction. On the basis of effective compounds, PLS, MLR and PCR were applied to establish the calibration models. The UVE-SPA-MLR model was the optimal method to predict the antioxidant activity values with Rp of 0.9200, 0.9010 and 0.8905 for DPPH, ABTS and FRAP assays, respectively. The results revealed that the UPLC-PDA/QTOF-MS combined with chemometrics could be a new method to classify the varieties and predict the antioxidant activity of O. fragrans flowers. PMID- 27664664 TI - Inhibitory effect of chlorogenic acid on digestion of potato starch. AB - The effect of the chlorogenic acid isomer 5-O-caffeoylquinic acid (5-CQA) on digestion of potato starch by porcine pancreatic alpha amylase (PPAA) was investigated using isolated starch and cooked potato tuber as substrates. In vitro digestion was performed on five varieties of potato with varying phenolic content. Co- and pre-incubation of PPAA with 5-CQA significantly reduced PPAA activity in a dose dependent manner with an IC50 value of about 2mgmL(-1). Lineweaver-Burk plots indicated that 5-CQA exerts a mixed type inhibition as km increased and Vmax decreased. The total polyphenol content (TPC) of peeled tuber tissue ranged from 320.59 to 528.94mg 100g(-1)dry weight (DW) in raw tubers and 282.03-543.96mg 100g(-1)DW in cooked tubers. With the exception of Desiree, TPC and 5-CQA levels decreased after cooking. Principle component analysis indicated that digestibility is affected by multiple factors including phenolic, dry matter and starch content. PMID- 27664666 TI - Preparation of SERS-active substrates based on graphene oxide/silver nanocomposites for rapid zdetection of l-Theanine. AB - A kind of graphene oxide/silver (GO/Ag) nanocomposites with high Surface enhanced Raman scattering (SERS) activity were fabricated via a facile and green liquid phase reduction method. The synthesized materials were characterized in detail using various microscopic and spectroscopic techniques. In this method, the GO sheets worked as a holder which makes silver nanoparticles (AgNPs) aggregate to a particular morphology, and under a suitable dosage of silver ions, well-dispersed AgNPs on the surface of GO were obtained, which could generate more "hot spots" of SERS. Moreover, SERS technique based on the obtained GO/Ag nanocomposites was used as an effective way to detect l-Theanine. The detection limit was estimated to be as low as 10(-7)M, and a multivariate linear regression model for the concentration of l-Theanine was established. The optimal fitting equation is Y=5.6765+0.0307X1458-0.0267X1251. PMID- 27664665 TI - Comparison of gravimetric, creamatocrit and esterified fatty acid methods for determination of total fat content in human milk. AB - The gravimetric method is considered the gold standard for measuring the fat content of human milk. However, it is labor intensive and requires large volumes of human milk. Other methods, such as creamatocrit and esterified fatty acid assay (EFA), have also been used widely in fat analysis. However, these methods have not been compared concurrently with the gravimetric method. Comparison of the three methods was conducted with human milk of varying fat content. Correlations between these methods were high (r(2)=0.99). Statistical differences (P<0.001) were observed in the overall fat measurements and within each group (low, medium and high fat milk) using the three methods. Overall, stronger correlation with lower mean (4.73g/L) and percentage differences (5.16%) was observed with the creamatocrit than the EFA method when compared to the gravimetric method. Furthermore, the ease of operation and real-time analysis make the creamatocrit method preferable. PMID- 27664667 TI - Digestibility and antigenicity of beta-lactoglobulin as affected by heat, pH and applied shear. AB - Processing induced conformational changes can modulate digestibility of food allergens and thereby their antigenicity. Effect of different pH (3, 5, 7), temperature (room temperature, 120 degrees C) and shear (0s(-1), 1000s(-1)) on simulated gastrointestinal digestibility of beta-lg and post digestion antigenic characteristics have been studied. At all pH levels unheated beta-lg showed resistance to peptic digestion with high antigenic value while it was fairly susceptible to pancreatin with moderate reduction in antigenicity. Heating at 120 degrees C significantly improved both peptic and pancreatic digestion attributed to structural alterations that resulted in much lower antigenicity; the level of reduction being pH dependant. The lowest antigenicity was recorded at pH 5. Shearing (1000s(-1)) had a minor impact reducing digestibility and thereby enhancing antigenicity of unheated beta-lg at pH 5 and 7 slightly; however in conjunction with heating (120 degrees C) it reduced antigenicity further irrespective of the pH. Overall, treatment at pH 5, 120 degrees C and 1000s(-1) could potentially reduce post digestion antigenicity of beta-lg. PMID- 27664668 TI - Extraction and determination of arsenic species in leafy vegetables: Method development and application. AB - Extraction of arsenic (As) species in leafy vegetables was investigated by different combinations of methods and extractants. The extracted As species were separated and determined by HPLC-ICP-MS method. The microwave assisted method using 1% HNO3 as the extractant exhibited satisfactory efficiency (>90%) at 90 degrees C for 1.5h. The proposed method was applied for extracting As species from real leafy vegetables. Thirteen cultivars of leafy vegetables were collected and analyzed. The predominant species in all the investigated vegetable samples were As(III) and As(V). Moreover, both As(III) and As(V) concentrations were positive significant (p<0.01) correlated with total As (tAs) concentration. However, the percentage of As(V) reduced with tAs concentration increasing probably due to the conversion and transformation of As(V) to As(III) after uptake. The hazard quotient results indicated no particular risk to 94.6% of local consumers. Considerably carcinogenic risk by consumption of the leafy vegetables was observed. PMID- 27664669 TI - Potential of different mechanical and thermal treatments to control off-flavour generation in broccoli puree. AB - The aim of this study was scientifically investigate the impact of the sequence of different thermo-mechanical treatments on the volatile profile of differently processed broccoli puree, and to investigate if any relationship persists between detected off-flavour changes and microstructural changes as a function of selected process conditions. Comparison of the headspace GC-MS fingerprinting of the differently processed broccoli purees revealed that an adequate combination of processing steps allows to reduce the level of off-flavour volatiles. Moreover, applying mechanical processing before or after the thermal processing at 90 degrees C determines the pattern of broccoli tissue disruption, resulting into different microstructures and various enzymatic reactions inducing volatile generation. These results may aid the identification of optimal process conditions generating a reduced level of off-flavour in processed broccoli. In this way, broccoli can be incorporated as a food ingredient into mixed food products with limited implications on sensorial consumer acceptance. PMID- 27664670 TI - Protein-transitions in and out of the dough matrix in wheat flour mixing. AB - Sequential protein behavior in the wheat dough matrix under continuous mixing and heating treatment has been studied using Mixolab-dough samples from two Australian wheat cultivars, Westonia and Wyalkatchem. Size exclusion high performance liquid chromatography (SE-HPLC) and two-dimensional gel electrophoresis (2-DGE) analysis indicated that 32min (80 degrees C) was a critical time point in forming large protein complexes and loosing extractability of several protein groups like y-type high molecular weight glutenin subunits (HMW-GSs), gamma-gliadins, beta-amylases, serpins, and metabolic proteins with higher mass. Up to 32min (80 degrees C) Westonia showed higher protein extractability compared to Wyalkatchem although it was in the opposite direction thereafter. Twenty differentially expressed proteins could be assigned to chromosomes 1D, 3A, 4A, 4B, 4D, 6A, 6B, 7A and 7B. The results expanded the range of proteins associated with changes in the gluten-complex during processing and provided targets for selecting new genetic variants associated with altered quality attributes of the flour. PMID- 27664671 TI - Ultrasound-assisted extraction of natural antioxidants from the flower of Limonium sinuatum: Optimization and comparison with conventional methods. AB - Natural antioxidants are widely used as dietary supplements or food additives. An optimized method of ultrasound-assisted extraction (UAE) was proposed for the effective extraction of antioxidants from the flowers of Limonium sinuatum and evaluated by response surface methodology. In this study, ethanol concentration, ratio of solvent to solid, ultrasonication time and temperature were investigated and optimized using a central composite rotatable design. The optimum extraction conditions were as follows: ethanol concentration, 60%; ratio of solvent to solid, 56.9:1mL/g; ultrasonication time, 9.8min; and temperature, 40 degrees C. Under the optimal UAE conditions, the experimental values (483.01+/ 15.39MUmolTrolox/gDW) matched with those predicted (494.13MUmolTrolox/gDW) within a 95% confidence level. In addition, the antioxidant activities of UAE were compared with those of conventional maceration and Soxhlet extraction methods, and the ultrasound-assisted extraction could give higher yield of antioxidants and markedly reduce the extraction time. PMID- 27664672 TI - A functional natural deep eutectic solvent based on trehalose: Structural and physicochemical properties. AB - In this study, the natural deep eutectic solvents (NADESs) based on trehalose and choline chloride have been prepared to enhance the protein thermostability. The results of fourier transform infrared spectroscopy and (1)H nuclear magnetic resonance spectroscopy suggested that there were intensive hydrogen-bonding interactions between trehalose and choline chloride in TCCL3-DES and TCCL3-DES75. The physicochemical properties of TCCL3-DES and TCCL3-DES75 were investigated in the temperature range of 293.15-363.15K. Our results revealed that the thermostability of lysozyme, a model protein used in this study was dramatically increased in TCCL3-DES75, as evidenced by the disappearance of the denaturing peak from their Differential Scanning Calorimetry (DSC) traces. The results of circular dichroism (CD) experiments further demonstrated that the lysozyme in TCCL3-DES75 unfolded partially at 90 degrees C and recovered to the initial structure at 20 degrees C. The study suggests that TCCL3-DES75 might be a potential solvent for stabilizing proteins. PMID- 27664673 TI - Chemometric evaluation of trace metals in Prunus persica L. Batech and Malus domestica from Minicevo (Serbia). AB - The samples of spatial soils and different organs of Prunus persica L. Batech and Malus domestica were analyzed by methods such as inductively coupled plasma optical emission spectroscopy (ICP-OES), Hierarchical Cluster Analysis (HCA), One way ANOVA, and calculation of biological accumulation factors (BAFs) with the aim of investigating whether these methods may help in the evaluation of trace metals in plants, as well as in the estimation of plant bioaccumulation potentials. ICP OES provided accurate data on present concentrations of Cu, Zn, Pb, As, Cd, and Ni which showed that most concentrations were in normal ranges, except in some cases for Cu, Zn, and As. HCA illustrated nicely various specifics in the distribution of metals in both investigated systems plant-soil. One-way ANOVA pointed successfully on the existing statistical differences between metal concentrations. Calculated BAFs showed that both plants had very low accumulation rates for all elements; they acted as metal excluders. PMID- 27664675 TI - The addition of rosehip oil to Aloe gels improves their properties as postharvest coatings for maintaining quality in plum. AB - The effect of Aloe vera gel (AV) and Aloe arborescens gel (AA) alone or in combination with rosehip oil (RO) at 2% on ethylene production, respiration rate, quality parameters, bioactive compounds and antioxidant activity during plum postharvest storage was studied. Coated plums showed a delay in ethylene production and respiration rate at 20 degrees C and during cold storage and subsequent shelf life, the main effect being observed for those fruits coated with AA+RO. Quality parameters such as softening, colour and maturity index was also delayed during storage by the use of the coatings, which led to a 2-fold increase in plum storability. Accumulation of bioactive compounds was also delayed although at the end of the experiment the content of bioactive compounds was higher than those found for control fruits at the estimated shelf life. The most effective coating for maintaining plum quality and bioactive compounds was AA+RO. PMID- 27664674 TI - A potential food biopreservative, CecXJ-37N, non-covalently intercalates into the nucleotides of bacterial genomic DNA beyond membrane attack. AB - The antibacterial activities and mechanism of an amide-modified peptide CecXJ-37N were investigated in this study. CecXJ-37N showed small MICs (0.25-7.8MUM) against eight harmful strains common in food industry. The alpha-helix proportion of CecXJ-37N increased by 11-fold in prokaryotic membrane comparable environments; cytotoxicity studies demonstrated the MHC was significantly higher than that of non-amidated isoform. Moreover, CecXJ-37N possessed stronger capacities to resist trypsin and pepsin hydrolysis within two hours. Flow cytometry and scanning electron microscopy demonstrated that CecXJ-37N induced pore-formation, morphological changes, and lysed E. coli cells. Fluorescence microscopy indicated that CecXJ-37N penetrated E. coli membrane and accumulated in cytoplasm. Further ultraviolet-visible spectroscopy suggested that CecXJ-37N changed the action mode of parental peptide interacting with bacterial genome from outside binding to a tightly non-covalent intercalation into nucleotides. Overall, this study suggested that amide-modification enhanced antimicrobial activity and reduced the cytotoxicity, thus could be potential strategies for developing novel food preservatives. PMID- 27664676 TI - Ultrasonication of reconstituted whole milk and its effect on acid gelation. AB - Ultrasonication (US) of whole milk at 22.5kHz and 50W homogenized fat globules. Extended US without temperature control (attaining >90 degrees C at longest times), or with control at temperatures ?60 degrees C caused denaturation of the whey proteins and aggregation of the fat globules and proteins. Acidification of US milk produced gels with increased firmness and reduced gelation times compared to untreated milk. Below 60 degrees C, US of milk produced acid gels with very high firmness without whey protein denaturation; the firmness was similar to gels from heated whole milk. Extensive US without temperature control or with control at ?60 degrees C decreased acid gel firmness compared to shorter times or lower temperatures. Higher acid gel firmness could be achieved by subjecting the milk to separate heat (80 degrees C/30min) and US treatment (at 20 degrees C) before acidification when compared with either heating or US alone. This was independent of the order of heating and US treatment. PMID- 27664677 TI - Effect of hydroxytyrosol and olive leaf extract on 1,2-dicarbonyl compounds, hydroxymethylfurfural and advanced glycation endproducts in a biscuit model. AB - The antiglycative activity of hydroxytyrosol (HT) and olive leaf extract (OLE) was investigated in wheat-flour biscuits. Quercetin (QE) and gallic acid (GA) were used as reference of antiglycative activity of phenolic compounds. HT, OLE, QE and GA were added in the range of 0.25-0.75% (w/w). Samples were compared against a control recipe baked at 180 degrees C/20min. HT biscuit was able to inhibit efficiently the formation of hydroxymethylfurfural (HMF) and 3 deoxyglucosone (3-DG), as well as reduced the formation of overall free fluorescent AGEs and pentosidine. The inhibition of the 3-DG and HMF formation was directly and significantly correlated under controlled baking conditions. However, samples formulated with OLE exerted similar antiglycative capacity against pentosidine and Nepsilon-carboxyethyl-lysine, although the amount of HT in the biscuit was 100-fold lower than the biscuit formulated with HT. Methylglyoxal, 3-DG, and glyoxal were the predominant 1,2-dicarbonyl compounds after baking but only 3-DG was significantly reduced by HT. PMID- 27664678 TI - Natural variation in folate levels among tomato (Solanum lycopersicum) accessions. AB - Folate content was estimated in tomato (Solanum lycopersicum) accessions using microbiological assay (MA) and by LC-MS. The MA revealed that in red-ripe fruits folate levels ranged from 4 to 60MUg/100g fresh weight. The LC-MS estimation of red-ripe fruits detected three folate forms, 5-CH3-THF, 5-CHO-THF, 5,10-CH(+)THF and folate levels ranged from 14 to 46MUg/100g fresh weight. In mature green and red ripe fruit, 5-CH3-THF was the most abundant folate form. Comparison of LC-MS with MA revealed that MA inaccurately estimates folate levels. The accumulation of folate forms and their distribution varied among accessions. The single nucleotide polymorphism was examined in the key genes of the folate pathway to understand its linkage with folate levels. Despite the significant variation in folate levels among tomato accessions, little polymorphism was found in folate biosynthesis genes. Our results indicate that variation in folate level is governed by a more complex regulation at cellular homeostasis level. PMID- 27664679 TI - A precise and efficient detection of Beta-Cyfluthrin via fluorescent molecularly imprinted polymers with ally fluorescein as functional monomer in agricultural products. AB - In this study, an effective and precise fluorescent molecularly imprinted polymers (FMIPs) for the determination of Beta-Cyfluthrin (BC) was synthesized via precipitation polymerization with SiO2 as the carrier, BC as the target molecule, ally fluorescein as the functional monomer, trimethylolpropane trimethacrylate (TRIM) as the crosslinker. Moreover, the characteristic of material has been measured by FTIR, TEM, SEM, TGA, LSCM and fluorescence spectrophotometer. Average diameter and shell thickness of as-synthesized microspheres were 300nm and 50nm, respectively. An excellent linear relationship of SiO2-MPTMS@FMIPs with a correlation coefficient of 0.9919 could be gained covering a wide concentration range of 10.11-80nM described by the Stern-Volmer equation. The limit of detection (LOD) was evaluated with the equation LOD=3sigma/S and was found to be 10.11nM. The study demonstrated that SiO2 MPTMS@FMIPs could improve the determination for BC and illustrated the good prospects of SiO2-MPTMS@FMIPs for BC detection in agricultural products. PMID- 27664680 TI - Development of molecular imprinted column-on line-two dimensional liquid chromatography for selective determination of clenbuterol residues in biological samples. AB - A novel method coupling molecular imprinted monolithic column with two dimensional liquid chromatography was developed and validated for the analysis of clenbuterol in pork liver and swine urine samples. The polymers were characterized by using Fourier transform infrared spectroscopy, nitrogen adsorption desorption analyses, frontal analysis and the adsorption of selectivity. The results indicated that the imprinted columns were well prepared and possessed high selectivity adsorption capacity. Subsequently, the MIMC-2D-LC (molecular imprinted monolithic column-two dimensional liquid chromatography) method was developed for the selective analysis of clenbuterol in practical samples. The accuracy ranged from 94.3% to 99.7% and from 93.7% to 99.6% for liver and urine, respectively. The relative standard deviation (RSD) of repeatability was lower than 8.6% for both analyses. The limit of detections was 16ng.mL(-1) for liver and 25ng.mL(-1) for urine, respectively. Compared with the reported methods, the disturbance of endogenous impurity could be avoided by the 2D-LC method. PMID- 27664681 TI - Influence of hydrogenated oil as cocoa butter replacers in the development of sugar-free compound chocolates: Use of inulin as stabilizing agent. AB - The effect of the addition of inulin as a surfactant or stability agent on white compound chocolate sweetened with sucralose and Stevia was studied. Samples were stored at 7, 15 and 30 degrees C during 100days and the influence of inulin on rheological properties, sensorial attributes, shelf-life, physical properties such as melting, crystallization and blooming were analyzed. The shelf-life of the compound chocolate with the incorporation of inulin was higher than the control sample without replacement. Compound chocolate with inulin at 10%w/w showed a dense matrix structure, reducing the size and number of fat crystals formed during storage; furthermore they presented higher values of brightness and WI. This chocolate also showed less fracturability and improved thermal properties. DSC studies revealed increased values of onset and peak temperatures and enthalpy of melting of the polymorphic form V, at higher storage temperatures, achieving greater stability against degradation processes. PMID- 27664682 TI - Reaction of zearalenone and alpha-zearalenol with allyl isothiocyanate, characterization of reaction products, their bioaccessibility and bioavailability in vitro. AB - This study investigates the reduction of zearalenone (ZEA) and alpha-zearalenol (alpha-ZOL) on a solution model using allyl isothiocyanate (AITC) and also determines the bioaccessibility and bioavailability of the reaction products isolated and identified by MS-LIT. Mycotoxin reductions were dose-dependent, and ZEA levels decreased more than alpha-ZOL, ranging from 0.2 to 96.9% and 0 to 89.5% respectively, with no difference (p?0.05) between pH 4 and 7. Overall, simulated gastric bioaccessibility was higher than duodenal bioaccessibility for both mycotoxins and mycotoxin-AITC conjugates, with duodenal fractions representing ?63.5% of the original concentration. Simulated bioavailability of reaction products (alpha-ZOL/ZEA-AITC) were lower than 42.13%, but significantly higher than the original mycotoxins. The cytotoxicity of alpha-ZOL and ZEA in Caco-2/TC7 cells was also evaluated, with toxic effects observed at higher levels than 75MUM. Further studies should be performed to evaluate the toxicity and estrogenic effect of alpha-ZOL/ZEA-AITC. PMID- 27664683 TI - Speciation of chromium in bread and breakfast cereals. AB - Bread and breakfast cereals are a major constituents of the human diet, yet their Cr(VI) content is not known. Chromium(VI) was determined in these products by high resolution continuum source atomic absorption spectrometer (HR-CS AAS) after leaching Cr(VI) with 0.10molL(-1) Na2CO3. The results showed that 33-73% of total Cr (58.17+/-5.12MUgkg(-1)-156.1+/-6.66MUgkg(-1)) in bread exist as Cr(VI) and the highest total Cr content was found in brown bread. It was shown that Cr(III) is oxidized to Cr(VI) during toasting of bread. Chromium(VI) content in breakfast cereals ranged between 20.4+/-4MUgkg(-1) and 470.4+/-68MUgkg(-1). Therefore, it can be concluded that bread and breakfast cereals contains Cr(VI) which does not exceed maximum acceptable concentration (MAC) of 0.003mgkg(-1)bw(-1)day(-1) through daily consumption of half a bowl (65g) of breakfast cereal and four slices of toasted (122g) or untoasted bread (160g). PMID- 27664684 TI - Application of matrix solid-phase dispersion followed by GC-MS/MS to the analysis of emerging contaminants in vegetables. AB - A multiresidue method for the determination of 17 emerging contaminants in vegetables was developed based on ultrasound-assisted matrix solid-phase dispersion (MSPD). The analysis was performed using isotope dilution gas chromatography tandem mass spectrometry. In the development of the MSPD procedure, different parameters such as sonication and the type of sorbent or extraction solvent were assayed. Manual and in situ derivatization was assayed and the chromatographic response was higher when the reaction takes place in the injection port. The limits of detection obtained for the studied compounds were in the range of 0.1-0.4ngg(-1) for the different vegetables analyzed. The developed method was applied to vegetables obtained from several local markets. At least one of the organophosphates was detected in the analyzed samples at levels ranging from 0.6 to 4.6ngg(-1) and bisphenol A was detected in all the samples at concentration up to 16ngg(-1). PMID- 27664685 TI - Improvement of texture and sensory properties of cakes by addition of potato peel powder with high level of dietary fiber and protein. AB - Demand for health oriented products such as low calories and high fiber product is increasing. The aim of the present work was to determine the effect of the addition of potato peel powders as protein and dietary fiber source on the quality of the dough and the cake. Powders obtained from the two types of peel flour showed interesting water binding capacity and fat absorption capacity. Potato peel flours were incorporated in wheat flours at different concentration. The results showed that peel powders additionally considerably improved the Alveograph profile of dough and the texture of the prepared cakes. In addition color measurements showed a significant difference between the control dough and the dough containing potato peels. The replacement of wheat flour with the potato powders reduced the cake hardness significantly and the L(*) and b(*) dough color values. The increased consumption of cake enriched with potato peel fiber is proposed for health reasons. The study demonstrated that protein/fiber-enriched cake with good sensory quality could be produced by the substitution of wheat flour by 5% of potato peel powder. In addition and technological point of view, the incorporation of potato peel powder at 5% increase the dough strength and elasticity-to-extensibility ratio (P/L). PMID- 27664686 TI - Effects of high pressure modification on conformation and gelation properties of myofibrillar protein. AB - The effects of high pressure (HP) treatment (100-500MPa) on conformation and gelation properties of myofibrillar protein (MP) were investigated. As pressure increased (0.1-500MPa), alpha-helix and beta-sheet changed into random coil and beta-turn, proteins unfolded to expose interior hydrophobic and sulfhydryl groups, therefore surface hydrophobicity and formation of disulfide bonds were strengthened. At 200MPa, protein solubility and gel hardness reached their maximum value, particle size had minimum value, and gel microstructure was dense and uniform. DSC data showed that actin and myosin completely denatured at 300MPa and 400MPa, respectively. Rheological modulus (G' and G") of HP-treated MP decreased as pressure increased during thermal gelation. Moderate HP treatment (?200MPa) strengthened gelation properties of MP, while stronger HP treatment (?300MPa) weakened the gelation properties. 200MPa was the optimum pressure level for modifying MP conformation to improve its gelation properties. PMID- 27664687 TI - Application of analytical methods in authentication and adulteration of honey. AB - Honey is synthesized from flower nectar and it is famous for its tremendous therapeutic potential since ancient times. Many factors influence the basic properties of honey including the nectar-providing plant species, bee species, geographic area, and harvesting conditions. Quality and composition of honey is also affected by many other factors, such as overfeeding of bees with sucrose, harvesting prior to maturity, and adulteration with sugar syrups. Due to the complex nature of honey, it is often challenging to authenticate the purity and quality by using common methods such as physicochemical parameters and more specialized procedures need to be developed. This article reviews the literature (between 2000 and 2016) on the use of analytical techniques, mainly NMR spectroscopy, for authentication of honey, its botanical and geographical origin, and adulteration by sugar syrups. NMR is a powerful technique and can be used as a fingerprinting technique to compare various samples. PMID- 27664688 TI - Double enzymatic hydrolysis preparation of heme from goose blood and microencapsulation to promote its stability and absorption. AB - Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide. This deficiency could be solved by preparing stable, edible, and absorbable iron food ingredients using environmentally friendly methods. This study investigated enzymatic hydrolysis and microencapsulation process of goose blood. The physicochemical properties, stabilities of the microencapsulated goose blood hydrolysate (MGBH) and a supplement for rats with IDA were also evaluated. The results showed that the synergetic hydrolytic action of neutrase and alkaline protease significantly increased the heme-releasing efficiency. The heme was then microencapsulated using sodium caseinate, maltodextrin and carboxymethyl cellulose (CMC) as the edible wall material, and the encapsulation efficiency of the product reached 98.64%. Meanwhile, favorable thermal, storage and light stabilities were observed for the microencapsulation. It was found that MGBH can significantly improve the body weight and hematological parameters of IDA Wistar rat. PMID- 27664689 TI - The polyphenolics and carbohydrates as indicators of botanical and geographical origin of Serbian autochthonous clones of red spice paprika. AB - Spice peppers (Capsicum annuum L.) var. Lemeska and Lakosnicka paprika were investigated to evaluate their polyphenolic and carbohydrate profiles and antioxidant activity. A total of forty-nine polyphenolics were identified using ultrahigh-performance liquid chromatography (UHPLC) coupled to LTQ OrbiTrap mass analyzer. Twenty-five of them were quantified using available standards, while the other compounds were confirmed by exact mass search of their deprotonated molecule [M-H](-) and its MS(4) fragmentation. Thirteen carbohydrates were quantified using high-performance anion exchange chromatography (HPAEC) with pulsed amperometric detection (PAD). Radical scavenging activity (RSA) ranged from 17.32 to 48.34mmol TE (Trolox equivalent)/kg DW (dry weight) and total phenolics content (TPC) was ranged between 7.03 and 14.92g GAE (gallic acid equivalents)/kg DW. To our best knowledge, five polyphenolic compounds were for the first time tentatively identified in paprika: 5-O-p-coumaroylquinic acid, luteolin 7-O-(2"-O-pentosyl-4"-O-hexosyl)hexoside, quercetin 3-O-(2"-O hexosyl)rhamnoside, isorhamnetin 3-O-[6"-O-(5-hydroxyferuloyl)hexoside]-7-O rhamnoside, and luteolin 7-O-[2"-O-(5'"-O-sinapoyl)pentosyl-6"-O malonyl]hexoside. PMID- 27664691 TI - Quality preservation of deliberately contaminated milk using thyme free and nanoemulsified essential oils. AB - The objective of this study is to evaluate the effect of either a solution of Thymus capitatus essential oil or its nanoemulsion on the quality of milk contaminated by bacteria. After 24h of S. aureus inoculation, bacterial growth reached 202*10(3)CFU/ml in the presence of the essential oil while it was limited to 132*10(3)CFU/ml when treated with nanoemulsion. The reduction of antioxidant capacity of milk treated with essential oil was higher when treated with nanoemulsion. Moreover, free essential oil was more efficient in protecting proteins from degradation than the nanoemulsion. For instance, after 24h of E. hirae contamination, 26% of the total proteins were consumed in the presence of nano-encapsulated essential oil, while only 14% of the initial content was consumed when free essential oil was added. Concerning milk acidity increase and the inhibition of peroxide production, no statistical differences have been recorded between the use of free essential oil or its nano-emulsion. In conclusion, bulk or nano-encapsulated T. capitatus essential oil preserve milk quality and can extend its shelf life. PMID- 27664690 TI - CYP2D6 and CYP2A6 biotransform dietary tyrosol into hydroxytyrosol. AB - The dietary phenol tyrosol has been reported to be endogenously transformed into hydroxytyrosol, a potent antioxidant with multiple health benefits. In this work, we evaluated whether tyrosine hydroxylase (TH) and cytochrome P450s (CYPs) catalyzed this process. To assess TH involvement, Wistar rats were treated with alpha-methyl-L-tyrosine and tyrosol. Tyrosol was converted into hydroxytyrosol whilst alpha-methyl-L-tyrosine did not inhibit the biotransformation. The role of CYP was assessed in human liver microsomes (HLM) and tyrosol-to-hydroxytyrosol conversion was observed. Screening with selective enzymatic CYP inhibitors identified CYP2A6 as the major isoform involved in this process. Studies with baculosomes further demonstrated that CYP2D6 and CYP3A4 could transform tyrosol into hydroxytyrosol. Experiments using human genotyped livers showed an interindividual variability in hydroxytyrosol formation and supported findings that CYP2D6 and CYP2A6 mediated this reaction. The dietary health benefits of tyrosol-containing foods remain to be evaluated in light of CYP pharmacogenetics. PMID- 27664692 TI - Continuous statistical modelling for rapid detection of adulteration of extra virgin olive oil using mid infrared and Raman spectroscopic data. AB - The main objective of this work was to develop a novel dimensionality reduction technique as a part of an integrated pattern recognition solution capable of identifying adulterants such as hazelnut oil in extra virgin olive oil at low percentages based on spectroscopic chemical fingerprints. A novel Continuous Locality Preserving Projections (CLPP) technique is proposed which allows the modelling of the continuous nature of the produced in-house admixtures as data series instead of discrete points. The maintenance of the continuous structure of the data manifold enables the better visualisation of this examined classification problem and facilitates the more accurate utilisation of the manifold for detecting the adulterants. The performance of the proposed technique is validated with two different spectroscopic techniques (Raman and Fourier transform infrared, FT-IR). In all cases studied, CLPP accompanied by k-Nearest Neighbors (kNN) algorithm was found to outperform any other state-of-the-art pattern recognition techniques. PMID- 27664693 TI - Oxidation of edible animal fats. Comparison of the performance of different quantification methods and of a proposed new semi-objective colour scale-based method. AB - The agreement among the results determined for the main parameters used in the evaluation of the fat auto-oxidation was investigated in animal fats (butter fat, subcutaneous pig back-fat and subcutaneous ham fat). Also, graduated colour scales representing the colour change during storage/ripening were developed for the three types of fat, and the values read in these scales were correlated with the values observed for the different parameters indicating fat oxidation. In general good correlation among the values of the different parameters was observed (e.g. TBA value correlated with the peroxide value: r=0.466 for butter and r=0.898 for back-fat). A reasonable correlation was observed between the values read in the developed colour scales and the values for the other parameters determined (e.g. values of r=0.320 and r=0.793 with peroxide value for butter and back-fat, respectively, and of r=0.767 and r=0.498 with TBA value for back-fat and ham fat, respectively). PMID- 27664694 TI - Milk from cows grazing on cool-season pastures provides an enhanced profile of bioactive fatty acids compared to those grazed on a monoculture of pearl millet. AB - The demand for dairy products from grass-fed cows is driven, in part, by their more desirable fatty acid (FA) profile, containing more n-3 FA and conjugated linoleic acids (CLA) than conventionally produced dairy products. This study investigated the effects of pearl millet (PM) vs. cool-season pasture (CSP) on animal performance and milk FA in a grazing system. Eight Holstein dairy cows were used in a repeated measures design with four-week periods. Forage type had no effect on animal performance (estimated dry matter intake, milk production, fat, or protein). The contents of CLA and n-3 FA in a serving of whole milk (3.25% fat) increased when cows grazed CSP compared to PM. A serving of whole milk from cows grazing PM had a higher content of saturated FA and branched-chain FA. In conclusion, the contents of various bioactive FA were higher in milk fat of cows grazing a CSP compared to PM. PMID- 27664695 TI - A comprehensive approach for milk adulteration detection using inherent bio physical properties as 'Universal Markers': Towards a miniaturized adulteration detection platform. AB - This paper proposes a novel milk quality detection approach based on utilization of inherent biophysical properties as 'markers' for adulteration. Unlike the traditional adulterant-specific approaches, this method is generic and universal. It exploits the change in innate milk properties, such as electrical conductivity and pH, upon addition of adulterants as a transduction mechanism for detecting milk adulteration. In this work, adulteration with more than 10 commercially known hazardous adulterants is detected by monitoring the changes in milk electrical conductivity and pH. The electrical parameters for pure milk were standardized using AC impedance-spectroscopy with glassy carbon working electrode and platinum counter/reference electrode at a potential of 0.3V and in the frequency range of 1Hz-1MHz. The experiments were repeated using gold-electrodes fabricated on glass-substrate as a first step towards developing a miniaturized platform. The concept of a 'unified-universal-marker' for successful prediction of adulteration is accentuated in this work. PMID- 27664696 TI - Combination of 1H NMR and chemometrics to discriminate manuka honey from other floral honey types from Oceania. AB - Manuka honey is a product produced essentially in New Zealand, and has been widely recognised for its antibacterial properties and specific taste. In this study, 264 honeys from New Zealand and Australia were analysed using proton NMR spectroscopy coupled with chemometrics. Known manuka markers, methylglyoxal and dihydroxyacetone, have been characterised and quantified, together with a new NMR marker, identified as being leptosperin. Manuka honey profiling using 1H NMR is shown to be a possible alternative to chromatography with the added advantage that it can measure methylglyoxal (MGO), dihydroxyacetone (DHA) and leptosperin simultaneously. By combining the information from these three markers, we established a model to estimate the proportion of manuka in a given honey. Markers of other botanical origins were also identified, which makes 1H NMR a convenient and efficient tool, complementary to pollen analysis, to control the botanical origin of Oceania honeys. PMID- 27664697 TI - Comparison of phytochemical profiles, antioxidant and cellular antioxidant activities of different varieties of blueberry (Vaccinium spp.). AB - Numerous reports have demonstrated that the consumption of fruits and vegetables is beneficial for the human health. Blueberries, in particular, are rich in phytochemicals including free and bound forming. Phytochemical profiles of 14 varieties of blueberry were compared in this study. 12 compounds were analyzed and had significant changes in blueberry fruits. Total antioxidant activities in different blueberry varieties varied about 2.6times by oxygen radical absorbance capacity (ORAC) assay, and 2times by peroxyl radical scavenging capacity (PSC) assay. The cellular antioxidant activities (CAA) in different varieties varied about 3.9times without phosphate buffer saline (PBS) wash, and 4.7times with PBS wash by CAA assay. Blueberry extracts had potent antiproliferative activities against HepG2 human liver cancer cells, indicating the potential protective benefits associated with their use as functional foods. The anti-proliferative activity was observed to be dose-dependent in blueberry extracts. PMID- 27664699 TI - Corrigendum to "Saffron authentication based on liquid chromatography high resolution tandem mass spectrometry and multivariate data analysis" [Food Chem. 204 (2016) 201-209]. PMID- 27664698 TI - Accumulation of guaiacol glycoconjugates in fruit, leaves and shoots of Vitis vinifera cv. Monastrell following foliar applications of guaiacol or oak extract to grapevines. AB - Previous studies have shown that volatile compounds present within a vineyard during the growing season can be absorbed by grapevines, assimilated within grapes, and then released during fermentation to influence the final aroma of wine. For example, the accumulation of volatile phenols in glycoconjugate forms following grapevine exposure to bushfire smoke, and their subsequent release during winemaking. This study investigated the accumulation of guaiacol glycoconjugates in the fruit, shoots and leaves of Monastrell grapevines following foliar applications (at veraison) of either an aqueous solution of guaiacol or an aqueous oak extract. Fruit, shoot and leaf samples were then collected at 3 time points between veraison and maturity, and analysed by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, to quantify guaiacol and its glycoconjugates, respectively. Guaiacol glycoconjugates were observed in fruit and leaves in particular, demonstrating glycosylation occurred after grapevine treatment; however, different glycoconjugate profiles were apparent. PMID- 27664701 TI - Ocular Hypotony in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis. AB - PURPOSE: To analyze occurrence, risk factors, and course of ocular hypotony (OH) in juvenile idiopathic arthritis-associated uveitis (JIAU). DESIGN: Cohort study. METHODS: Epidemiologic and ophthalmologic data at baseline and during follow-up of JIAU patients with and without ocular hypotony were evaluated. RESULTS: OH developed in 57 of the 365 JIAU patients during the follow-up (mean 4.5 +/- 3.5 years). In 40 patients with follow-up >=12 months, OH was unrelated to previous ocular surgery: risk factors at baseline (univariate logistic regression analysis) included longer total duration of uveitis (odds ratio [OR] 1.13, P < .001), bilateral uveitis (OR 3.51, P = .009), low visual acuity (OR 5.1, P = .001), high laser-flare (LF) values (OR 1.74, P = .01), and presence of posterior synechiae (OR 3.28, P = .004). Increased anterior chamber (AC) cell and LF values were observed within 3 months prior to onset of transient (<=3 months; 37.5%) or persistent OH (>3 months; 62.5%). AC cell and LF values decreased within 3 months after onset of transient OH, while LF levels remained elevated >=12 months in persistent OH. Optic disc edema and epiretinal membrane formation was found more frequently after OH onset. CONCLUSIONS: OH was observed in 15.6% of JIAU patients. Longer total uveitis duration, bilateral uveitis, low visual acuity, high AC flare and LF grades, and presence of posterior synechiae at baseline were risk factors for subsequent OH. Burden of OH might be improved with immunosuppression. PMID- 27664700 TI - Radiation protective effects of baclofen predicted by a computational drug repurposing strategy. AB - Exposure to ionizing radiation causes damage to living tissues; however, only a small number of agents have been approved for use in radiation injuries. Radioprotector is the primary countermeasure to radiation injury and none radioprotector has indeed reached the drug development stage. Repurposing the long list of approved, non-radioprotective drugs is an attractive strategy to find new radioprotective agents. Here, we applied a computational approach to discover new radioprotectors in silico by comparing publicly available gene expression data of ionizing radiation-treated samples from the Gene Expression Omnibus (GEO) database with gene expression signatures of more than 1309 small molecule compounds from the Connectivity Map (cmap) dataset. Among the best compounds predicted to be therapeutic for ionizing radiation damage by this approach were some previously reported radioprotectors and baclofen (P<0.01), a chemical that was not previously used as radioprotector. Validation using a cell based model and a rodent in vivo model demonstrated that treatment with baclofen reduced radiation-induced cytotoxicity in vitro (P<0.01), attenuated bone marrow damage and increased survival in vivo (P<0.05). These findings suggest that baclofen might serve as a radioprotector. The drug repurposing strategy by connecting the GEO data and cmap can be used to identify known drugs as potential radioprotective agents. PMID- 27664702 TI - Axial Length Measurement Failure Rates With Biometers Using Swept-Source Optical Coherence Tomography Compared to Partial-Coherence Interferometry and Optical Low Coherence Interferometry. AB - PURPOSE: To compare a new swept-source optical coherence tomography (SSOCT)-based biometer (OA-2000) with the IOLMaster v5.4 (partial-coherence interferometry) and Aladdin (optical low-coherence interferometry) biometers in terms of axial length measurement and failure rate in eyes with cataract. DESIGN: Reliability study. METHODS: A total of 377 eyes of 210 patients were scanned with the 3 biometers in a random order. For each biometer, the number of unobtainable axial length measurements was recorded and grouped as per the type and severity of cataract based on the Lens Opacities Classification System III by the same experienced ophthalmologist. The Bland-Altman limits-of-agreement (LoA) method was used to assess the agreement in axial length measurements between the 3 biometers. RESULTS: The failure rate was 0 eyes (0%) with the OA-2000, 136 eyes (36.07%) with the IOLMaster, and 51 eyes (13.53%) with the Aladdin. chi2 analyses indicated a significant difference in failure rate between all 3 devices (P < .001). Logistic regression analysis highlighted a statistically significant trend of higher failure rates with increasing severity of nuclear, cortical, and posterior subcapsular cataracts. Bland-Altman statistics indicated small mean differences and narrow LoA (OA-2000 vs IOLMaster -0.09 to 0.08 mm; OA-2000 vs Aladdin -0.10 to 0.07 mm; IOLMaster vs Aladdin -0.05 to 0.04 mm). CONCLUSIONS: The OA-2000, a new SSOCT-based biometer, outperformed both the IOLMaster and Aladdin biometers in very advanced cataracts of various morphologies. The use of SSOCT technology may be the reason for the improved performance of the OA-2000 and may lead to this technology becoming the gold standard for the measurement of axial length. PMID- 27664703 TI - Cyclic ADP-ribose and IP3 mediate abscisic acid-induced isoflavone accumulation in soybean sprouts. AB - In this study, the roles of ABA-cADPR-Ca2+ and ABA-IP3-Ca2+ signaling pathways in UV-B-induced isoflavone accumulation in soybean sprouts were investigated. Results showed that abscisic acid (ABA) up regulated cyclic ADP-ribose (cADPR) and inositol 1,4,5-trisphosphate (IP3) levels in soybean sprouts under UV-B radiation. Furthermore, cADPR and IP3, as second messengers of UV-B-triggered ABA, induced isoflavone accumulation by up-regulating proteins and genes expression and activity of isoflavone biosynthetic-enzymes (chalcone synthase, CHS; isoflavone synthase, IFS). After Ca2+ was chelated by EGTA, isoflavone content decreased. Overall, ABA-induced cADPR and IP3 up regulated isoflavone accumulation which was mediated by Ca2+ signaling via enhancing the expression of proteins and genes participating in isoflavone biosynthesis in soybean sprouts under UV-B radiation. PMID- 27664704 TI - Real-time imaging of mast cell degranulation in vitro and in vivo. AB - Mast cells undergo degranulation in response to various stimuli and rapidly release pre-formed mediators present in secretory granules, leading to immediate type allergic reactions. Mast cell degranulation is commonly detected and quantified in vitro by measuring histamine or beta-hexosaminidase released to culture medium. However, this type of assay cannot monitor degranulation of individual cells in real time, and it is not suitable for in vivo detection of degranulation. At the aim of real time imaging of mast cell degranulation at single cell level, we here developed a fluorescent protein-based indicator of degranulation, designated immuno-pHluorin (impH). When expressed in mast cells, impH is located in the membrane of secretory granules and non-fluorescent under homeostatic conditions while it turns fluorescent following degranulation, due to the pH change inside of granules during exocytosis. impH enabled us to detect polarized degranulation within one single cell when mast cells were stimulated via the small area of cell surface. Transplantation of impH-expressing mast cells into mast cell-deficient mice demonstrated that impH could function as a real time indicator of degranulation in vivo. Thus, impH is a useful tool for imaging of mast cell activation and degranulation in vitro and in vivo, and may be applied for screening of reagents regulating mast cell degranulation. PMID- 27664705 TI - Autophagy stimulated proliferation of porcine PSCs might be regulated by the canonical Wnt signaling pathway. AB - Porcine pancreatic stem cells (PSCs) are one kind of the potential cells for treatment of human diabetes. Autophagy is a highly conserved cellular degradation process in which it helps to maintain the balance between the synthesis, degradation and subsequent recycling of cellular components. However, how autophagy contributes to PSCs has not yet been investigated. Here, we established GFP-LC3 transfected porcine PSC lines in which the accumulation of autophagosomes can be efficiently visualized to evaluate the autophagic activity. Moreover, we observed that starved PSCs which showed increased autophagic activity exhibited an increased tendency to proliferate through the results of BrdU, flow cytometry and western blotting. Furthermore, increased expression of active beta-catenin after inducing autophagy indicated that it might be the canonical Wnt signaling that autophagy activated to exert the function on the stimulation of PSCs proliferation. Collectively, these results demonstrated that autophagy stimulated proliferation of PSCs might be regulated by the canonical Wnt signaling pathway. Our results for the first time shed light on a role of autophagy for stimulating the proliferation of porcine PSCs. PMID- 27664706 TI - Perivascular adipose tissue alleviates inflammatory factors and stenosis in diabetic blood vessels. AB - Adipose tissue can modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on the pathophysiology of blood vessel walls, remain to be determined. In this study, we aimed to investigate whether perivascular adipose tissue could have an ameliorative effect on blood vessels damaged in diabetes. Using in vitro coculture, and in vivo transplantation model simulating diabetic angioplasty induced injury, we showed that perivascular adipose tissue has an important function in protecting blood vessels from high glucose impairment. Levels of inflammatory cytokines, including intercellular cell adhesion molecule-1 and osteopontin, were markedly reduced, whereas that of endothelial nitric-oxide synthase was markedly elevated in vascular walls. These depot-specific differences in blood vessels exposed to high levels of glucose were demonstrable both in vivo, with transplanted adipose tissues, and in vitro, when vascular endothelial cells were cocultured with adipocytes. In addition, intimal hyperplasia was also decreased by transplanted perivascular adipose tissue after balloon injury combined with hyperglycemia. We conclude that perivascular adipocytes can reduce inflammation in blood vessels and promote the normal function of endothelium, which could afford a new therapeutic strategy in vascular walls damaged by diabetes. PMID- 27664707 TI - Identification and analysis of the metacaspase gene family in tomato. AB - Metacaspases play critical roles in developmentally regulated and environmentally induced programmed cell death in plants. In this study, we systematically identified and analyzed metacaspase gene family in tomato (Solanum lycopersicum). The results illustrated that tomato possesses eight metacaspase genes (SlMC1-8) located on chromosomes 1, 3, 5, 9, and 10. SlMC1-6 belonged to type I metacaspases and had 5 exon/4 intron structures. SlMC7 and 8 were type II metacaspases and had 2 and 3 exons, respectively. Expression analysis revealed distinct expression patterns of SlMCs in various tomato tissues. Cis-regulatory element prediction showed that there were many hormone- and stress-related cis regulatory elements in SlMCs promoter regions. Quantitative real-time PCR analysis further demonstrated that most of the SlMCs were regulated by drought, cold, salt, methyl viologen, and ethephon treatments. This study provides insights into the characteristics of SlMC genes and laid the foundation for further functional analysis of these genes in tomato. PMID- 27664708 TI - Research Waste in Atopic Eczema Trials-Just the Tip of the Iceberg. AB - Clinical trials often continue to be undertaken even though the effectiveness of the intervention under consideration has already been demonstrated. In addition, vehicle- or placebo-controlled studies predominate over head-to-head comparisons, although the latter would be more informative for clinicians in guiding patient management. This creates research waste, and both investigators and funders are to blame. Wilkes et al. used a network analysis approach to show duplication of effort in trials assessing topical calcineurin inhibitors and corticosteroids as treatment options for atopic eczema. Unfortunately, this is just the tip of the research waste iceberg. PMID- 27664709 TI - New Insights into the Molecular Distinction of Dysplastic Nevi and Common Melanocytic Nevi-Highlighting the Keratinocyte-Melanocyte Relationship. AB - Mitsui et al. approach the problem of differentiating dysplastic nevi from common melanocytic nevi through a molecular lens. Whereas most of the literature on this topic shines the spotlight toward melanocytes, the focus of this paper is shifted to the tumor microenvironment. Using microarrays, reverse transcriptase-PCR, and immunohistochemistry, their results emphasize the role of keratinocyte dysplasia within dysplastic nevi. PMID- 27664710 TI - NRAS, NRAS, Which Mutation Is Fairest of Them All? AB - In 28% of melanomas, NRAS is mutated in one of two hotspots: G12 or Q61. Phosphoproteomic analysis of primary human melanocytes transduced with G12 and Q61 showed different phosphorylation events in the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Surprisingly, NRAS(G12) modulates the PI3K pathway and overexpresses the kinase PIM2, whereas NRAS(Q61) is associated with the MAPK pathway and overexpression of CK2alpha. PMID- 27664711 TI - Mineralocorticoid Receptor Antagonists-A New Sprinkle of Salt and Youth. AB - Skin atrophy and impaired cutaneous wound healing are the recognized side effects of topical glucocorticoid (GC) therapy. Although GCs have high affinity for the glucocorticoid receptor, they also bind and activate the mineralocorticoid receptor. In light of this, one can speculate that some of the GC-mediated side effects can be remedied by blocking activation of the mineralocorticoid receptor. Indeed, according to Nguyen et al., local inhibition of the mineralocorticoid receptor via antagonists (spironolactone, canrenoate, and eplerenone) rescues GC induced delayed epithelialization and accelerates wound closure in diabetic animals by targeting epithelial sodium channels and stimulating keratinocyte proliferation. These findings suggest that the use of mineralocorticoid receptor antagonists coupled with GC therapy may be beneficial in overcoming at least some of the GC-mediated side effects. PMID- 27664715 TI - Research Techniques Made Simple: Laser Capture Microdissection in Cutaneous Research. AB - In cutaneous research, we aim to study the molecular signature of a diseased tissue. However, such a study is met with obstacles due to the inherent heterogeneous nature of tissues because multiple cell types reside within a tissue. Furthermore, there is cellular communication between the tissue and the neighboring extracellular matrix. Laser capture microdissection is a powerful technique that allows researchers to isolate cells of interest from any tissue using a laser source under microscopic visualization, thereby circumventing the issue of tissue heterogeneity. Target cells from fixed preparations can be extracted and examined without disturbing the tissue structure. In live cultures, a subpopulation of cells can be extracted in real time with minimal disturbance of cellular communication and molecular signatures. Here we describe the basic principles of the technique, the different types of laser capture microdissection, and the subsequent downstream analyses. This article will also discuss how the technique has been employed in cutaneous research, as well as future directions. PMID- 27664712 TI - Expanding the Mutation Spectrum of Ichthyosis with Confetti. AB - Ichthyosis with confetti is a rare, autosomal dominant disorder caused by frameshift mutations in KRT10 or KRT1 and characterized by the development of white, genetically revertant macules in red, diseased skin. All cases result from mutations affecting the tail domains of keratin-10 or keratin-1, and Suzuki et al. expand the mutation spectrum for ichthyosis with confetti caused by mutations in KRT1, showing that a polyarginine frameshift in the keratin-1 tail can also cause this disorder. PMID- 27664716 TI - Impairment of decision making and disruption of synchrony between basolateral amygdala and anterior cingulate cortex in the maternally separated rat. AB - There is considerable evidence to suggest early life experiences, such as maternal separation (MS), play a role in the prevalence of emotional dysregulation and cognitive impairment. At the same time, optimal decision making requires functional integrity between the amygdala and anterior cingulate cortex (ACC), and any dysfunction of this system is believed to induce decision-making deficits. However, the impact of MS on decision-making behavior and the underlying neurophysiological mechanisms have not been thoroughly studied. As such, we consider the impact of MS on the emotional and cognitive functions of rats by employing the open-field test, elevated plus-maze test, and rat gambling task (RGT). Using multi-channel recordings from freely behaving rats, we assessed the effects of MS on the large scale synchrony between the basolateral amygdala (BLA) and the ACC; while also characterizing the relationship between neural spiking activity and the ongoing oscillations in theta frequency band across the BLA and ACC. The results indicated that the MS rats demonstrated anxiety-like behavior. While the RGT showed a decrease in the percentage of good decision makers, and an increase in the percentage of poor decision-makers. Electrophysiological data revealed an increase in the total power in the theta band of the LFP in the BLA and a decrease in theta power in the ACC in MS rats. MS was also found to disrupt the spike-field coherence of the ACC single unit spiking activity to the ongoing theta oscillations in the BLA and interrupt the synchrony in the BLA-ACC pathway. We provide specific evidence that MS leads to decision-making deficits that are accompanied by alteration of the theta band LFP in the BLA-ACC circuitries and disruption of the neural network integrity. These observations may help revise fundamental notions regarding neurophysiological biomarkers to treat cognitive impairment induced by early life stress. PMID- 27664717 TI - Orexin receptor expression in the hypothalamic-pituitary-adrenal and hypothalamic pituitary-gonadal axes of free-living European beavers (Castor fiber L.) in different periods of the reproductive cycle. AB - Orexins are hypothalamic neuropeptides acting via two G protein-coupled receptors in mammals: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). In European beavers, which are seasonally breeding animals, the presence and functions of orexins and their receptors remain unknown. Our study aimed to determine the expression of OXR mRNAs and the localization of OXR proteins in hypothalamic pituitary-adrenal/gonadal (HPA/HPG) axes in free-living beavers. The expression of OXR genes (OX1R, OX2R) and proteins was found in all analysed tissues during three periods of beavers' reproductive cycle (April, July, November). The expression of OXR mRNAs in the beaver HPA axis varied seasonally (P<0.05). The levels of OX1R mRNA also differed between the sexes (P<0.05). In the mediobasal hypothalamus, OX1R transcript content increased in pregnant females in April (P<0.05) and OX2R expression increased in males in July (P<0.05). In the pituitary and adrenals, OX1R mRNA levels were relatively constant in females and peaked in July in males (P<0.05), whereas the OX2R was most highly expressed in males in November and in females in April (P<0.05). In gonads, OX1R expression did not fluctuate between seasons or sexes, but transcript levels were elevated in the testes in November and in the ovaries in July (P<0.05). In turn, OX2R mRNA levels varied between the sexes (P<0.05) and were higher in females (July and November) than in males (P<0.05). The circannual variations in OXR mRNA levels in HPA and HPG axes suggest that the expression of these receptors is associated with sex-specific changes in beavers' reproductive activity and their environmental adaptations. PMID- 27664718 TI - Differential expression of pectolytic enzyme genes in Xanthomonas citri subsp. citri and demonstration that pectate lyase Pel3 is required for the formation of citrus canker. AB - Bacterial canker, caused by Xanthomonas citri subsp. citri (Xcc), is one of the most destructive diseases of citrus. The pectolytic enzymes produced by phytobacteria are important virulence factors involved in tissue maceration, electrolyte loss and cell death of host plants. In this study, the promoter activity of the pectolytic enzyme genes pel1, pel2, pel3, pglA, and peh-1 were investigated in Xcc XW19 strain using the beta-glucuronidase (GUS) gene as a reporter. GUS activity expressed under the control of the pel1, pel3, pglA, and peh-1 gene promoters positively correlated with bacterial growth. These gene promoters displayed high GUS activity in the presence of sodium polypectate. In addition, the four genes were induced in XVM2 minimal medium. However, only pel1 was subjected to catabolite repression by glucose. GUS activity was significantly enhanced in the XW19-derived reporter strains after they were inoculated into the leaves of Mexican lime and grapefruit, suggesting the involvement of the pel1, pel3, pglA, and peh-1 genes in XW19 pathogenesis. The pel3 promoter produced the highest GUS activity under all test conditions, whereas no GUS activity was detected using the pel2 promoter in vitro and in planta. In comparison with wild type Xcc, a pel3 mutant generated from Xcc XW19 using unmarked mutagenesis displayed reduced growth and induced smaller canker lesions on the leaves of Mexican lime, demonstrating that Pel3 of Xcc strain XW19 is a virulence factor. PMID- 27664719 TI - Adenylyl cyclase is required for cAMP production, growth, conidial germination, and virulence in the citrus green mold pathogen Penicillium digitatum. AB - Penicillium digitatum is the causative agent of green mold decay on citrus fruit. The cAMP-mediated signaling pathway plays an important role in the transduction of extracellular signals and has been shown to regulate a wide range of developmental processes and pathogenicity in fungal pathogens. We cloned and characterized a Pdac1 gene of P. digitatum, which encodes a polypeptide similar to fungal adenylyl cyclases. Using a loss-of-function mutation in the Pdac1 gene we demonstrated a critical requirement for hyphal growth and conidial germination. Deletion of Pdac1 resulted in decreased accumulation of cAMP and down-regulation of genes encoding a G protein alpha subunit, both catalytic and regulatory subunits of PKA, and two transcriptional regulators StuA and Som1. Fungal mutants lacking Pdac1 produced abundant conidia, which failed to germinate effectively and displayed an elevated sensitivity to heat treatment. Pdac1 mutant failed to utilize carbohydrates effectively and thus displayed severe growth retardation on rich and synthetic media. Slow growth seen in the Pdac1 mutants could be due to a defect in nutrient sensing and acquisition. Quantitative RT-PCR analysis revealed that Pdac1 was primarily expressed at the early stage of infection. Fungal pathogenicity assayed on citrus fruit revealed that P. digitatum strains impaired for Pdac1 delayed lesion formation. Our results highlight important regulatory roles of adenylyl cyclase-mediated cAMP production in P. digitatum and provide insights into the critical role of cAMP in fungal growth, development and virulence. PMID- 27664720 TI - Phosphatidylcholine affects the secretion of the alkaline phosphatase PhoA in Pseudomonas strains. AB - Pseudomonas aeruginosa ATCC 27853 and Pseudomonas sp. 593 use the phosphatidylcholine synthase pathway (Pcs-pathway) for the biosynthesis of phosphatidylcholine (PC). Both bacterial strains contain the phoA and lapA genes encoding alkaline phosphatases (ALP) and display strong ALP activities. The PhoA and LapA enzymes are thought to be independently secreted via the Xcp and Hxc type II secretion system (T2SS) subtypes, in which the Hxc system may act as a complementary mechanism when the Xcp pathway becomes limiting. Inactivation of the pcs gene in both bacteria abolished PC synthesis and resulted in approximately 50% less ALP activity in the cell-free culture. Analysis by western blotting showed that LapA protein content in the wild type and the pcs- mutant was unchanged in the cytoplasmic, periplasmic or extracellular protein fractions. In contrast, the PhoA protein in the pcs- mutant was less prevalent among extracellular proteins but was more abundant in the periplasmic protein fraction compared to the wild type. Semi- quantitative reverse transcriptase PCR showed that phoA, lapA and 12 xcp genes were equally expressed at the transcriptional level in both the wild types and the pcs- mutants. Our results demonstrate that the absence of PC in bacterial membrane phospholipids does not interfere with the transcription of the phoA and lapA genes but primarily affects the export of PhoA from the cytoplasm to the extracellular environment via the Xcp T2SS. PMID- 27664721 TI - Bacillus velezensis RC 218 as a biocontrol agent to reduce Fusarium head blight and deoxynivalenol accumulation: Genome sequencing and secondary metabolite cluster profiles. AB - Bacillus subtilis RC 218 was originally isolated from wheat anthers as a potential antagonist of Fusarium graminearum, the causal agent of Fusarium head blight (FHB). It was demonstrated to have antagonist activity against the plant pathogen under in vitro and greenhouse assays. The current study extends characterizing B. subtilis RC 218 with a field study and genome sequencing. The field study demonstrated that B. subtilis RC 218 could reduce disease severity and the associated mycotoxin (deoxynivalenol) accumulation, under field conditions. The genome sequencing allowed us to accurately determine the taxonomy of the strain using a phylogenomic approach, which places it in the Bacillus velezensis clade. In addition, the draft genome allowed us to use bioinformatics to mine the genome for potential metabolites. The genome mining allowed us to identify 9 active secondary metabolites conserved by all B. velezensis strains and one additional secondary metabolite, the lantibiotic ericin, which is unique to this strain. This study represents the first confirmed production of ericin by a B. velezensis strain. The genome also allowed us to do a comparative genomics with its closest relatives and compare the secondary metabolite production of the publically available B. velezensis genomes. The results showed that the diversity in secondary metabolites of strains in the B. velezensis clade is driven by strains making different antibacterials. PMID- 27664722 TI - Endophytic and rhizosphere bacteria associated with the roots of the halophyte Salicornia europaea L. - community structure and metabolic potential. AB - The main objective of our study was to assess density and diversity of rhizosphere (R) and endophytic (E) microorganisms associated with the halophyte S. europaea. Microorganisms were isolated from two saline sites (S1: 55dSm(-1), anthropogenic origin; S2: 112dSm(-1), natural salinity) located in central Poland and compared with microbial populations in the soil (S) using culture-independent (phospholipid fatty acids analysis, PLFA) and culture-dependent techniques. The endophytic and rhizosphere bacteria were identified and screened for nifH and acdS genes, and their metabolic properties were assessed. Strains with the potential to promote plant growth were selected for further study. PLFA analysis revealed that Gram-negative bacteria were dominant at both saline test sites; the total microbial biomass depended on the site (S1E>S). In contrast, culture-dependent techniques revealed that Gram-positive bacteria (Actinobacteria and Firmicutes) were dominant (S1: E-77.3%, R-86.3% and S2: E-59.1%, R-87.5%). Proteobacteria were observed in the rhizosphere at the lowest frequency (S1: 13.7% and S2: 12.5%). Greater salinity decreased the range and specificity of metabolic activity among the endophytes. These conditions also resulted in a broader spectrum of metabolic abilities in rhizobacteria; however, these metabolic processes were present at lower levels. PMID- 27664723 TI - Phytogenic synthesis of silver nanoparticles, optimization and evaluation of in vitro antifungal activity against human and plant pathogens. AB - An attempt was made to synthesis of biocompatible silver nanoparticles from ten different Cassia spp. Among them, Cassia roxburghii aqueous leaf extract supported the synthesis of highly efficient and stable AgNPs. The synthesis of AgNPs was optimized at different physico-chemical condition and highly stable AgNPs were synthesized with 1.0mL of C. roxburghii leaf extract, pH 7.0, 1.0mM AgNO3 and at 37 degrees C. The synthesized AgNPs were characterized by XPS, DLS and ZETA potential. DLS and ZETA potential analysis, the average AgNPs size was 35nm and the zeta potential was -18.3mV. The AgNPs exhibit higher antifungal activity when compared with the conventional antifungal drug amphotericin B against all the tested human fungal pathogens such as Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Penicillium sp., Candida albicans and the plant pathogens such as Rhizoctonia solani, Fusarium oxysporum and Curvularia sp. Scanning electron microscope (SEM) analysis showed distinct structural changes in the cell membranes of C. albicans upon AgNPs treatment. These results suggest that phytosynthesized AgNPs could be used as effective growth inhibitors in controlling various human and plant diseases caused by fungi. PMID- 27664724 TI - Significance of hyphae formation in virulence of Candida tropicalis and transcriptomic analysis of hyphal cells. AB - Recently, the proportion of Candida tropicalis in clinical isolates has significantly increased. Some C. tropicalis strains colonize the skin or mucosal surfaces as commensals; others trigger invasive infection. To date, the pathogenicity of C. tropicalis has not been thoroughly researched. This study reports several virulence factors, including biofilm and hyphae formation, proteinase, phospholipase, lipase and hemolytic activity, in 52 clinical isolates of C. tropicalis collected from five hospitals in four provinces of China. Some C. tropicalis tended to produce more hyphae than others in the same circumstance. Six C. tropicalis strains with different morphologies were injected into mice via the tail vein, and the survival proportions and fungal burdens of the strains were evaluated. Hyphal production by C. tropicalis was associated with stronger virulence. RNA sequencing revealed that C. tropicalis with more hyphae up regulated several genes involved in morphological differentiation and oxidative response, including IF2, Atx1, and Sod2. It appears that hyphal formation plays a vital role in the pathogenicity of C. tropicalis, and interacts with the oxidative stress response to strengthen the organism's virulence. PMID- 27664725 TI - Do cultural conditions induce differential protein expression: Profiling of extracellular proteome of Aspergillus terreus CM20. AB - The present study reports the diversity in extracellular proteins expressed by the filamentous fungus, Aspergillus terreus CM20 with respect to differential hydrolytic enzyme production profiles in submerged fermentation (SmF) and solid state fermentation (SSF) conditions, and analysis of the extracellular proteome. The SSF method was superior in terms of increase in enzyme activities resulting in 1.5-3 fold enhancement as compared to SmF, which was explained by the difference in growth pattern of the fungus under the two culture conditions. As revealed by zymography, multiple isoforms of endo-beta-glucanase, beta glucosidase and xylanase were expressed in SSF, but not in SmF. Extracellular proteome profiling of A. terreus CM20 under SSF condition using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) identified 63 proteins. Functional classification revealed the hydrolytic system to be composed of glycoside hydrolases (56%), proteases (16%), oxidases and dehydrogenases (6%), decarboxylases (3%), esterases (3%) and other proteins (16%). Twenty families of glycoside hydrolases (GH) (1, 3, 5, 7, 10, 11, 12, 15, 16, 28, 30, 32, 35, 43, 54, 62, 67, 72, 74 and 125), and one family each of auxiliary activities (AA7) and carbohydrate esterase (CE1) were detected, unveiling the vast diversity of synergistically acting biomass-cleaving enzymes expressed by the fungus. Saccharification of alkali-pretreated paddy straw with A. terreus CM20 proteins released high amounts of glucose (439.63+/-1.50mg/gds), xylose (121.04+/ 1.25mg/gds) and arabinose (56.13+/-0.56mg/gds), thereby confirming the potential of the enzyme cocktail in bringing about considerable conversion of lignocellulosic polysaccharides to sugar monomers. PMID- 27664726 TI - Role of ppGpp in Pseudomonas aeruginosa acute pulmonary infection and virulence regulation. AB - During infection, bacteria might generate adaptive responses to facilitate their survival and colonization in the host environment. The alarmone guanosine 5' triphosphate-3'-diphosphate (ppGpp), the levels of which are regulated by the RelA and SpoT enzymes, plays a critical role in mediating bacterial adaptive responses and virulence. However, the mechanism by which ppGpp regulates virulence-associated traits in Pseudomonas aeruginosa is poorly understood. To investigate the regulatory role of ppGpp, the ppGpp-deficient strain DeltaRS (relA and spoT gene double mutant) and the complemented strain DeltaRS(++) (complemented with relA and spoT genes) were constructed. Herein, we reported that the DeltaRS strain showed decreased cytotoxicity towards A549 human alveolar adenocarcinoma cell lines and led to reduced mortality, lung edema and inflammatory cell infiltration in a mouse model of acute pneumonia compared to wild-type PAO1 and the complemented strain DeltaRS(++). Subsequent analyses demonstrated that the DeltaRS strain displayed reduced T3SS expression, decreased levels of elastase activity, pyocyanin, pyoverdin and alginate, and inhibited swarming and biofilm formation compared to PAO1 and the complemented strain DeltaRS(++). In addition, the results demonstrate that ppGpp-mediated regulation of T3SS, virulence factor production, and swarming occurs in a quinolone quorum sensing system-dependent manner. Taken together, these results suggest that ppGpp is required for virulence regulation in P. aeruginosa, providing new clues for the development of interference strategies against bacterial infection. PMID- 27664727 TI - Overexpression of a pathway specific negative regulator enhances production of daunorubicin in bldA deficient Streptomyces peucetius ATCC 27952. AB - The dnrO gene is the first regulator to be activated in the daunorubicin (DNR) biosynthesis pathway of Streptomyces peucetius ATCC 27952. DnrO is known for its self-repression capability while it activates rest of the DNR biosynthesis pathway through cascades of regulatory events. S. peucetius was found to contain no functional copy of bldA-tRNA while a detailed examination of dnrO codons reveals the presence of TTA codon, which is rarely encoded by bldA-tRNA. Therefore, for evaluating the role of dnrO in DNR production, multiple engineered strains of S. peucetius were generated by heterologously expressing bldA, dnrO and combination of bldA and dnrO. Using these strains, the effects of heterologously expressed bldA and overexpressed dnrO were evaluated on pathway specific regulators, mycelial densities and production of DNR. The results showed that the transcription level of dnrO and master regulator dnrI, was found to be elevated in bldA containing strain in comparison to dnrO overexpressed strain. The bldA containing strain produces 45.7% higher DNR than bldA deficient wild type strain from culture broth with OD600 of 1.45 at 72h. Heterologous expression of bldA-tRNA is accounted for increased transcription levels of the DNR pathway specific regulators and enhanced DNR production. PMID- 27664728 TI - Volatile organic compounds produced by Pseudomonas fluorescens WR-1 restrict the growth and virulence traits of Ralstonia solanacearum. AB - The volatile organic compounds (VOCs) produced by soil microbes have a significant role in the control of plant diseases and plant growth promotion. In this study, we examined the effect of VOCs produced by Pseudomonas fluorescens strain WR-1 on the growth and virulence traits of tomato wilt pathogen Ralstonia solanacearum. The VOCs produced by P. fluorescens WR-1 exhibited concentration dependent bacteriostatic effect on the growth of R. solanacearum on agar medium and in infested soil. The VOCs of P. fluorescens WR-1 also significantly inhibited the virulence traits of R. solanacearum. The proteomics analysis showed that the VOCs of P. fluorescens WR-1 downregulated cellular proteins of R. solanacearum related to the antioxidant activity, virulence, inclusion body proteins, carbohydrate and amino acid synthesis and metabolism, protein folding and translation, methylation and energy transfer, while the proteins involved in the ABC transporter system, detoxification of aldehydes and ketones, protein folding and translation were upregulated. This study revealed the significance of VOCs of P. fluorescens WR-1 to control the tomato wilt pathogen R. solanacearum. Investigation of the modes of action of biocontrol agents is important to better comprehend the interactions mediated by VOCs in nature to design better control strategies for plant pathogens. PMID- 27664729 TI - Indentification of vincamine indole alkaloids producing endophytic fungi isolated from Nerium indicum, Apocynaceae. AB - Vincamine, a monoterpenoid indole alkaloid which had been marketed as nootropic drugs for the treatment of cerebral insufficiencies, is widely found in plants of the Apocynaceae family. Nerium indicum is a plant belonging to the Apocynaceae family. So, the purpose of this research was designed to investigate the vincamine alkaloids producing endophytic fungi from Nerium indicum, Apocynaceae. 11 strains of endophytic fungi, isolated from the stems and roots of the plant, were grouped into 5 genera on the basis of morphological characteristics. All fungal isolates were fermented and their extracts were preliminary screened by Dragendorff's reagent and thin layer chromatography (TLC). One isolated strain CH1, isolated from the stems of Nerium indicum, had the same Rf value (about 0.56) as authentic vincamine. The extracts of strain CH1 were further analyzed by high performance liquid chromatography (HPLC) and liquid chromatograph-mass spectrometry (LC-MS), and the results showed that the strain CH1 could produce vincamine and vincamine analogues. The acetylcholinesterase (AchE) inhibitory activity assays using Ellman's method revealed that the metabolites of strain CH1 had significant AchE inhibitory activity with an IC50 value of 5.16MUg/mL. The isolate CH1 was identified as Geomyces sp. based on morphological and molecular identification, and has been deposited in the China Center for Type Culture Collection (CCTCCM 2014676). This study first reported the natural compounds tabersonine and ethyl-vincamine from endophytic fungi CH1, Geomyces sp. In conclusion, the fungal endophytes from Nerium indicum can be used as alternative source for the production of vincamine and vincamine analogues. PMID- 27664731 TI - Royal Jelly: An ancient remedy with remarkable antibacterial properties. AB - Royal Jelly (RJ), a honeybee hypopharyngeal gland secretion of young nurse and an exclusive nourishment for bee queen, has been used since ancient times for care and human health and it is still very important in traditional and folkloristic medicine, especially in Asia within the apitherapy. Recently, RJ and its protein and lipid components have been subjected to several investigations on their antimicrobial activity due to extensive traditional uses and for a future application in medicine. Antimicrobial activities of crude Royal Jelly, Royalisin, 10-hydroxy-2-decenoic acid, Jelleines, Major Royal Jelly Proteins against different bacteria have been reported. All these beehive products showed antimicrobial activities that lead their potential employment in several fields as natural additives. RJ and its derived compounds show a highest activity especially against Gram positive bacteria. The purpose of this Review is to summarize the results of antimicrobial studies of Royal Jelly following the timescale of the researches. From the first scientific applications to the isolation of the single components in order to better understand its application in the past years and propose an employment in future studies as a natural antimicrobial agent. PMID- 27664730 TI - Transcriptome sequencing analysis of novel sRNAs of Kineococcus radiotolerans in response to ionizing radiation. AB - Kineococcus radiotolerans is a Gram-positive, radio-resistant bacterium isolated from a radioactive environment. The small noncoding RNAs (sRNAs) in bacteria are reported to play roles in the immediate response to stress and/or the recovery from stress. The analysis of K. radiotolerans transcriptome sequencing results can identify these sRNAs in a genome-wide detection, using RNA sequencing (RNA seq) by the deep sequencing technique. In this study, the raw data of radiation exposed samples (RS) and control samples (CS) were acquired separately from the sequencing platform. There were 217 common sRNA candidates in the two samples screened in the genome-wide scale by bioinformatics analysis. There were 43 differentially expressed sRNA candidates, including 28 up-regulated and 15 down regulated ones. The down-regulated sRNAs were selected for the sRNA target prediction, of which 12 sRNAs that may modulate the genes related to the transcription regulation and DNA repair were considered as the candidates involved in the radio-resistance regulation system. PMID- 27664732 TI - Identification of genes associated with asexual reproduction in Phyllosticta citricarpa mutants obtained through Agrobacterium tumefaciens transformation. AB - Phyllosticta citricarpa is the epidemiological agent of Citrus Black Spot (CBS) disease, which is responsible for large economic losses worldwide. CBS is characterized by the presence of spores (pycnidiospores) in dark lesions of fruit, which are also responsible for short distance dispersal of the disease. The identification of genes involved in asexual reproduction of P. citricarpa can be an alternative for directional disease control. We analyzed a library of mutants obtained through Agrobacterium tumefaciens transformation system, looking for alterations in growth and reproductive structure formation. Two mutant strains were found to have lost the ability to form pycnidia. The flanking T-DNA insertion regions were identified on P. citricarpa genome by using blast analysis and further gene prediction. The predicted genes containing the T-DNA insertions were identified as Spindle Poison Sensitivity Scp3, Ion Transport protein, and Cullin Binding proteins. The Ion Transport and Cullin Binding proteins are known to be correlated with sexual and asexual reproduction in fungi; however, the exact mechanism by which these proteins act on spore formation in P. citricarpa needs to be better characterized. The Scp3 proteins are suggested here for the first time as being associated with asexual reproduction in fungus. This protein is associated with microtubule formation, and as microtubules play an essential role as spindle machinery for chromosome segregation and cytokinesis, insertions in this gene can lead to abnormal formations, such as that observed here in P. citricarpa. We suggest these genes as new targets for fungicide development and CBS disease control, by iRNA. PMID- 27664733 TI - Antagonist effects of Bacillus spp. strains against Fusarium graminearum for protection of durum wheat (Triticum turgidum L. subsp. durum). AB - Bacillus species are attractive due to their potential use in the biological control of fungal diseases. Bacillus amyloliquefaciens strain BLB369, Bacillus subtilis strain BLB277, and Paenibacillus polymyxa strain BLB267 were isolated and identified using biochemical and molecular (16S rDNA, gyrA, and rpoB) approaches. They could produce, respectively, (iturin and surfactin), (surfactin and fengycin), and (fusaricidin and polymyxin) exhibiting broad spectrum against several phytopathogenic fungi. In vivo examination of wheat seed germination, plant height, phenolic compounds, chlorophyll, and carotenoid contents proved the efficiency of the bacterial cells and the secreted antagonist activities to protect Tunisian durum wheat (Triticum turgidum L. subsp. durum) cultivar Om Rabiia against F. graminearum fungus. Application of single bacterial culture medium, particularly that of B. amyloliquefaciens, showed better protection than combinations of various culture media. The tertiary combination of B. amyloliquefaciens, B. subtilis, and P. polymyxa bacterial cells led to the highest protection rate which could be due to strains synergistic or complementary effects. Hence, combination of compatible biocontrol agents could be a strategic approach to control plant diseases. PMID- 27664734 TI - Bifidobacteria-Insight into clinical outcomes and mechanisms of its probiotic action. AB - The invasion of pathogens causes a disruption of the gut homeostasis. Innate immune responses and those triggered by endogenous microbiota form the first line of defence in our body. Pathogens often successfully overcome the resistances offered, calling for therapeutic intervention. Conventional strategy involving antibiotics might eradicate pathogens, but often leave the gut uncolonised and susceptible to recurrences. Probiotic supplements are useful alternatives. Bifidobacterium is one of widely studied probiotic genus, effective in restoring gut homeostasis. Mechanisms of probiotic action of bifidobacteria are several, often with strain-specificity. Analysis of streamlined literature reports reveal that although most studies report the probiotic aspect of bifidobacteria, sporadic documented contradictory results exist, challenging its therapeutic application and prompting studies to unambiguously establish the strain associated probiotic activity and negate adverse effects prior to its clinical administration. Multi-strain/combinatorial therapy possibly relies on a combination of underlying operating mechanisms, each contributing towards enhanced probiotic efficacy, understanding which could help in developing customised formulations against targeted pathogens. Bifidogenic activity is also mediated by surface-associated structural components such as exopolysaccharides, lipoteichoic acids along with metabolites and bifidocins. This highlights scope for developing advanced structural therapeutic strategy which might be pivotal in replacing intact cell probiotics therapy. PMID- 27664735 TI - Screening and modes of action of antagonistic bacteria to control the fungal pathogen Phaeomoniella chlamydospora involved in grapevine trunk diseases. AB - The antagonistic activity of 46 bacterial strains isolated from Bordeaux vineyards were evaluated against Phaeomoniella chlamydospora, a major grapevine pathogen involved in Esca. The reduction of the necrosis length of stem cuttings ranged between 31.4% and 38.7% for the 8 most efficient strains. Two in planta trials allowed the selection of the two best strains, Bacillus pumilus (S32) and Paenibacillus sp. (S19). Their efficacy was not dependent on application method; co-inoculation, prevention in the wood and soil inoculation were tested. The involvement of antibiosis by the secretion of diffusible and/or volatile compounds in the antagonistic capacity of these two strains was assessed in vitro. Volatile compounds secreted by B. pumilus (S32) and Paenibacillus sp. (S19) were identified by gas chromatography/mass spectroscopy (GC/MS). The volatile compounds 1-octen-3-ol and 2,5-dimethyl pyrazine were obtained commercially and tested, and they showed strong antifungal activity against P. chlamydospora, which suggested that these compounds may play an important role in the bacterial antagonistic activity in planta. Furthermore, the expression of 10 major grapevine defense genes was quantified by real-time polymerase chain reaction, which demonstrated that the two strains significantly affected the grapevine transcripts four days after their application on the plants. High expression levels of different genes associated with P. chlamydospora infection in B. pumilus pre-treated plants suggests that this strain induces systemic resistance in grapevine. For the first time, we demonstrated the ability of two bacterial strains, B. pumilus and Paenibacillus sp., isolated from grapevine wood, to control P. chlamydospora via direct and/or indirect mechanisms. PMID- 27664736 TI - Novel strategy to detect and locate periodontal pathogens: The PNA-FISH technique. AB - PURPOSE: We aim to develop peptic nucleic acid (PNA) probes for the identification and localization of Aggregatibacter actinomycetemcomintans and Porphyromonas gingivalis in sub-gingival plaque and gingival biopsies by Fluorescence in situ Hybridization (FISH). METHODS: A PNA probe was designed for each microorganism. The PNA-FISH method was optimized to allow simultaneous hybridization of both microorganisms with their probe (PNA-FISH multiplex). After being tested on representative strains of P. gingivalis and A. actinomycetemcomitans, the PNA-FISH method was then adapted to detect microorganisms in the subgingival plaque and gingival samples, collected from patients with severe periodontitis. RESULTS: The best hybridization conditions were found to be 59 degrees C for 150min for both probes (PgPNA1007 and AaPNA235). The in silico sensitivity and specificity was both 100% for PgPNA1007 probe and 100% and 99.9% for AaPNA235 probe, respectively. Results on clinical samples showed that the PNA-FISH method was able to detect and discriminate target bacteria in the mixed microbial population of the subgingival plaque and within periodontal tissues. CONCLUSION: This investigation presents a new highly accurate method for P. gingivalis and A. actinomycetemcomitans detection and co location in clinical samples, in just few hours. With this technique we were able to observe spatial distribution of these species within polymicrobial communities in the periodontal pockets and, for the first time with the FISH method, in the organized gingival tissue. PMID- 27664737 TI - Microbial communities associated with Antarctic snow pack and their biogeochemical implications. AB - Snow ecosystems represent a large part of the Earth's biosphere and harbour diverse microbial communities. Despite our increased knowledge of snow microbial communities, the question remains as to their functional potential, particularly with respect to their role in adapting to and modifying the specific snow environment. In this work, we investigated the diversity and functional capabilities of microorganisms from 3 regions of East Antarctica, with respect to compounds present in snow and tested whether their functional signature reflected the snow environment. A diverse assemblage of bacteria (Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, Deinococcus-Thermus, Planctomycetes, Verrucomicrobia), archaea (Euryarchaeota), and eukarya (Basidiomycota, Ascomycota, Cryptomycota and Rhizaria) were detected through culture-dependent and -independent methods. Although microbial communities observed in the three snow samples were distinctly different, all isolates tested produced one or more of the following enzymes: lipase, protease, amylase, beta-galactosidase, cellulase, and/or lignin modifying enzyme. This indicates that the snow pack microbes have the capacity to degrade organic compounds found in Antarctic snow (proteins, lipids, carbohydrates, lignin), thus highlighting their potential to be involved in snow chemistry. PMID- 27664738 TI - Comparative genome analysis of the oleaginous yeast Trichosporon fermentans reveals its potential applications in lipid accumulation. AB - In this work, Trichosporon fermentans CICC 1368, which has been shown to accumulate cellular lipids efficiently using industry-agricultural wastes, was subjected to preliminary genome analysis, yielding a genome size of 31.3 million bases and 12,702 predicted protein-coding genes. Our analysis also showed a high degree of gene duplications and unique genes compared with those observed in other oleaginous yeasts, with 3-4-fold more genes related to fatty acid elongation and degradation compared with those in Rhodosporidium toruloides NP11 and Yarrowia lipolytica CLIB122. Phylogenetic analysis with other oleaginous microbes suggested that the lipogenic capacity of T. fermentans was obtained during evolution after the divergence of genera. Thus, our study provided the first draft genome and comparative analysis of T. fermentans, laying the foundation for its genetic improvement to facilitate cost-effective lipid production. PMID- 27664739 TI - Organic acid mediated repression of sugar utilization in rhizobia. AB - Rhizobia are a class of symbiotic diazotrophic bacteria which utilize C4 acids in preference to sugars and the sugar utilization is repressed as long as C4 acids are present. This can be manifested as a diauxie when rhizobia are grown in the presence of a sugar and a C4 acid together. Succinate, a C4 acid is known to repress utilization of sugars, sugar alcohols, hydrocarbons, etc by a mechanism termed as Succinate Mediated Catabolite Repression (SMCR). Mechanism of catabolite repression determines the hierarchy of carbon source utilization in bacteria. Though the mechanism of catabolite repression has been well studied in model organisms like E. coli, B. subtilis and Pseudomonas sp., mechanism of SMCR in rhizobia has not been well elucidated. C4 acid uptake is important for effective symbioses while mutation in the sugar transport and utilization genes does not affect symbioses. Deletion of hpr and sma0113 resulted in the partial relief of SMCR of utilization of galactosides like lactose, raffinose and maltose in the presence of succinate. However, no such regulators governing SMCR of glucoside utilization have been identified till date. Though rhizobia can utilize multitude of sugars, high affinity transporters for many sugars are yet to be identified. Identifying high affinity sugar transporters and studying the mechanism of catabolite repression in rhizobia is important to understand the level of regulation of SMCR and the key regulators involved in SMCR. PMID- 27664741 TI - Unraveling the predator-prey relationship of Cupriavidus necator and Bacillus subtilis. AB - Cupriavidus necator is a non-obligate bacterial predator of Gram-negative and Gram-positive bacteria. In this study, we set out to determine the conditions, which are necessary to observe predatory behavior of C. necator. Using Bacillus subtilis as a prey organism, we confirmed that the predatory performance of C. necator is correlated with the available copper level, and that the killing is mediated, at least in part, by secreted extracellular factors. The predatory activity depends on the nutrition status of C. necator, but does not require a quorum of predator cells. This suggests that C. necator is no group predator. Further analyses revealed that sporulation enables B. subtilis to avoid predation by C. necator. In contrast to the interaction with predatory myxobacteria, however, an intact spore coat is not required for resistance. Instead resistance is possibly mediated by quiescence. PMID- 27664740 TI - Bacillus amyloliquefaciens SB14 from rhizosphere alleviates Rhizoctonia damping off disease on sugar beet. AB - The use of biocontrol strains recently has become a popular alternative to conventional chemical treatments. A set of bacteria isolated from sugar beet rhizosphere and from roots and shoots of apple and walnut were evaluated for their potential to control sugar beet seedling damping-off caused by R. solani AG 4 and AG2-2.The results of in vitro assays concluded that three isolates, SB6, SB14, SB15, obtained from rhizosphere of sugar beet and five isolates, AP2, AP4, AP6, AP7, AP8, obtained from shoots and roots of apple were the most effective antagonists that inhibited the mycelial growth of both R. solani isolates. Combination of several biochemical tests and partial sequencing of 16S rRNA and gyrBgenes revealed that eight efficient bacterial isolates could be assigned to the genus Bacillus and all could tolerate high temperatures and salt concentrations in their vegetative growth. The potential biocontrol activity of the eight bacterial antagonists were tested in greenhouse condition. The results indicated that four strains,B. amyloliquefaciens SB14, B. pumilus SB6,B. siamensis AP2 and B. siamensisAP8 exerted a significant influence on controlling of seedling damping-off and performed significantly better than others.However, the treatment of the seeds with bacteria was most effective when the isolate SB14 was used, which significantly controlled damping-off disease by 58% caused by R. solani AG-4 and by 52.5% caused by R. solani AG-2-2. This indicates that the use of beneficial bacterial native to the host plant may increase the success rate in screening biocontrols, because these microbes are likely to be better adapted to their host and its associated environmental conditions than are strains isolated from other plant species grown in different environmental conditions. We can infer from the results reported here that sugar beet plantsmay recruitbeneficial microbes to the rhizosphere to help them solve context-specific challenges. PMID- 27664742 TI - Utilization of physiological and taxonomic fluorescent probes to study Lactobacilli cells and response to pH challenge. AB - pH stress is recognized as an important feature for Lactobacillus in relation to lifestyle and commercial utility. Hence, this study aims to investigate the cell function of Lactobacilli cells subjected to pHs between 7.0 and 2.0. For this purpose, the Lactobacilli isolates of vegetable origin were first hybridized with fluorescent oligonucleotide rRNA probes for detecting Lactobacillus species. Then, cells were exposed to pH stress and labelled with fluorescent probes, carboxyfluorescein diacetate (CFDA) and propidium iodine (PI), which provided the insight into esterase activity and membrane integrity of cells. Among isolates, fluorescence in situ hybridization (FISH) enabled us to specifically detect L. plantarum and L. brevis. Interestingly, FCM analysis revealed that at pHs between 7.0 and 4.0 the cell membrane was intact, while after the exposure at pH 3.0, and 2.0 became perturbed or impaired. Finally, L. brevis and L. plantarum differed from each other in fluorescence labeling behaviour and culturability. However, the results showed that the same standard protocol for labeling enables discrimination of subpopulations of tested species. Depending on the species, the substantial culturability loss was observed at pH 3.0 and 2.0. These results suggest that the taxonomic and physiological fluorescent probes could be suitable for in situ detection of specific bacteria and rapid assessment of the physiological status of cells. PMID- 27664744 TI - Mycoplasmal lipoprotein p37 binds human protein HER2. AB - Mycoplasmas are a group of microbes that can cause human diseases. The mycoplasmal lipoprotein p37 promotes cancer metastasis, at least in part, by interacting with EGFR. In this study, we show that the p37 lipoprotein binds another member of the EGFR family, HER2, through the HER2 extracellular domain. The binding of p37-HER2 promotes phosphorylation of HER2 and activates the downstream signaling molecule Erk1/2. Because the HER2 signaling pathway contributes to breast tumor metastasis, our results imply that the mycoplasmal lipoprotein p37 may also be involved in breast cancer metastasis. This study contributes to our understanding of mycoplasmal lipoprotein p37 function and its potential involvement in tumorigenesis. PMID- 27664743 TI - Evaluation of in vitro and in vivo nematicidal potential of a multifunctional streptomycete, Streptomyces hydrogenans strain DH16 against Meloidogyne incognita. AB - The present work demonstrated the nematicidal potential of Streptomyces hydrogenans strain DH16 (a strain with strong antagonism against fungal phytopathogens and insect pest) against Meloidogyne incognita. The culture supernatant and solvent extract significantly inhibited egg hatching (almost 100%) along with J2 mortality of more than 95% after 96h. The nematicidal activity of 10-(2,2-dimethyl-cyclohexyl)-6,9-dihydroxy-4,9-dimethyl-dec-2-enoic acid methyl ester (SH2; a new antifungal compound) purified from this streptomycete was also evaluated using different concentrations. The juvenile mortality of the nematode increased with increasing concentration and exposure time and reached the maximum (95%) after 96h at concentration of 100MUg/ml. After 160h of incubation, egg hatch of 16% was observed at concentration of 100MUg/ml as compared to control where 100% egg hatching was achieved. However, at the highest concentration of the compound (200MUg/ml), 100% J2 mortality and 0% egg hatching were observed after 72 and 160h of incubation, respectively. In vivo pot experiments further revealed the nematicidal potential of S. hydrogenans where soil drenching with its culture supernatant and cells effectively controlled root galls, egg masses in nematode infested tomato plants and at the same time promoted the growth of tomato plants. Additionally, in the absence of nematodes, soil drenching with culture supernatant and cells significantly enhanced the various agronomic traits of plants as compared to control plants. Thus, the outcomes of the current study endorse the potential of S. hydrogenans strain DH16 and its metabolites to be developed as safe nematicidal and plant growth promoting agents. PMID- 27664745 TI - Biocontrol and plant growth promoting activities of a Streptomyces corchorusii strain UCR3-16 and preparation of powder formulation for application as biofertilizer agents for rice plant. AB - Streptomyces corchorusii strain UCR3-16, obtained from rice rhizospheric soils showed antifungal activities against 6 major rice fungal pathogens by diffusible and volatile compounds production. The strain was found positive for production of fungal cell wall degrading enzymes such as chitinase, beta-1,3-glucanase, beta 1,4-glucanase, lipase and protease. The strain was also positive for plant growth promoting traits. It produced up to 30.5MUg/ml of IAA and solubilized a significant amount of inorganic phosphate (up to 102MUg/ml). It also produced 69% siderophore units. The strain also produced ammonia and gave positive result for ACC deaminase activity. Highest vigor index of inoculated seedlings was observed when rice seeds were treated with cell suspension of UCR3-16 corresponding to 4.5*10(8)cfu/ml. Bioinoculant-treated seeds also showed similar results under pathogen challenged conditions. In pot trial experiments, UCR3-16-treated rice plants showed significantly increased growth and grain yield production. Powder formulation of the strain was developed using talcum and corn starch as carriers and the shelf-lives were monitored. Talcum formulation showed higher cell-count than corn starch even after 6 months of storage, and optimum condition for storage of the powder formulation were found to be at 4 degrees C. Pot trial experiments using talcum powder formulation also showed significant positive effects on growth of rice plants. Field trial using talcum powder formulation also exhibited significant enhancement in shoot length and weight of shoot and root, and total grain yield and weight of grains in rice plants. Talcum formulation also significantly reduced the sheath blight disease in rice leaves. PMID- 27664746 TI - Bacterial polyhydroxyalkanoates: Still fabulous? AB - Bacterial polyhydroxyalkanoates (PHA) are polyesters accumulated as carbon and energy storage materials under limited growth conditions in the presence of excess carbon sources. They have been developed as biomaterials with unique properties for the past many years being considered as a potential substitute for conventional non-degradable plastics. Due to the increasing concern towards global climate change, depleting petroleum resource and problems with an utilization of a growing number of synthetic plastics, PHAs have gained much more attention from industry and research. These environmentally friendly microbial polymers have great potential in biomedical, agricultural, and industrial applications. However, their production on a large scale is still limited. This paper describes the backgrounds of PHAs and discussed the current state of knowledge on the polyhydroxyalkanoates. Ability of bacteria to convert different carbon sources to PHAs, the opportunities and challenges of their introduction to global market as valuable renewable products have been also discussed. PMID- 27664748 TI - Transcriptomic analysis for elucidating the physiological effects of 5 aminolevulinic acid accumulation on Corynebacterium glutamicum. AB - 5-Aminolevulinic acid (ALA), the committed intermediate of the heme biosynthetic pathway, attracts close attention among researchers because of its potential applications to cancer treatment and agriculture. Overexpression of heterologous hemA and hemL, which encode glutamyl-tRNA reductase and glutamate-1-semialdehyde aminotransferase, respectively, in Corynebacterium glutamicum produces ALA, although whether ALA accumulation causes unintended effects on the host is unknown. Here we used an integrated systems approach to compare global transcriptional changes induced by the expression of hemA and hemL. Metabolic pathway such as glycolysis was inhibited, but tricarboxylic acid cycle, pentose phosphate pathway, and respiratory metabolism were stimulated. Moreover, the transcriptional levels of certain genes involved in heme biosynthesis were up regulated, and the data implicate the two-component system (TCS) HrrSA was involved in the regulation of heme synthesis. With these understandings, it is proposed that ALA accumulation stimulates heme synthesis pathway and respiratory metabolism. Our study illuminates the physiological effects of overexpressing hemA and hemL on the phenotype of C. glutamicum and contributes important insights into the regulatory mechanisms of the heme biosynthetic pathways. PMID- 27664747 TI - The DNA-mimic antirestriction proteins ArdA ColIB-P9, Arn T4, and Ocr T7 as activators of H-NS-dependent gene transcription. AB - The antirestriction proteins ArdA ColIb-P9, Arn T4 and Ocr T7 specifically inhibit type I and type IV restriction enzymes and belong to the family of DNA mimic proteins because their three-dimensional structure is similar to the double helical B-form DNA. It is proposed that the DNA-mimic proteins are able to bind nucleoid protein H-NS and alleviate H-NS-silencing of the transcription of bacterial genes. Escherichia coli lux biosensors were constructed by inserting H NS-dependent promoters into a vector, thereby placing each fragment upstream of the promoterless Photorhabdus luminescens luxCDABE operon. It was demonstrated that the DNA-mimic proteins ArdA, Arn and Ocr activate the transcription of H-NS dependent promoters of the lux operon of marine luminescent bacteria (mesophilic Aliivibrio fischeri and psychrophilic Aliivibrio logei), and the dps gene from E. coli. It was also demonstrated that the ArdA antirestriction protein, the genes of which are located on transmissive plasmids ColIb-P9, R64, PK101, decreases levels of H-NS silencing of the PluxC promoter during conjugation in the recipient bacteria. PMID- 27664750 TI - Bacterial community analysis of an industrial wastewater treatment plant in Colombia with screening for lipid-degrading microorganisms. AB - The operation of wastewater treatment technologies depends on a combination of physical, chemical and biological factors. Microorganisms present in wastewater treatment plants play essential roles in the degradation and removal of organic waste and xenobiotic pollutants. Several microorganisms have been used in complementary treatments to process effluents rich in fats and oils. Microbial lipases have received significant industrial attention because of their stability, broad substrate specificity, high yields, and regular supply, as well as the fact that the microorganisms producing them grow rapidly on inexpensive media. In Colombia, bacterial community studies have focused on populations of cultivable nitrifying, heterotrophic and nitrogen-fixing bacteria present in constructed wetlands. In this study, culture-dependent methods, culture independent methods (TTGE, RISA) and enzymatic methods were used to estimate bacterial diversity, to monitor temporal and spatial changes in bacterial communities, and to screen microorganisms that presented lipolytic activity. The dominant microorganisms in the Wastewater Treatment Plant (WWTP) examined in this study belonged to the phyla Firmicutes, Proteobacteria and Bacteroidetes. The enzymatic studies performed indicated that five bacterial isolates and three fungal isolates possessed the ability to degrade lipids; additionally, the Serratia, Kosakonia and Mucor genera presented lipase-mediated transesterification activity. The implications of these findings in regard to possible applications are discussed later in this paper. Our results indicate that there is a wide diversity of aerobic Gram-negative bacteria inhabiting the different sections of the WWTP, which could indicate its ecological condition, functioning and general efficiency. PMID- 27664749 TI - Bio-protective microbial agents from rhizosphere eco-systems trigger plant defense responses provide protection against sheath blight disease in rice (Oryza sativa L.). AB - Sheath blight of rice (Oryza sativa L.) caused by Rhizoctonia solani is a major disease and attempts are being made to develop microbe based technologies for biocontrol of this pathogen. However, the mechanisms of biocontrol are not fully understood and still require indepth study in the backdrop of emerging concepts in biological systems. The present investigation was aimed at deciphering the mechanisms of biocontrol of sheath blight of rice employing Pseudomonas fluorescens and Trichoderma harzianum as model agents for biocontrol. Initially 25, 5 and 5 strains of P. fluorescens, T. viride and T. harzianum, respectively, were screened for their biocontrol potential. Out of which, six strains with higher value of percent inhibition of fungal mycelium in dual plate assay were selected. The role of P. fluorescens, T. viride and T. harzianum were investigated in induction and bioaccumulation of natural antioxidants, defence related biomolecules and other changes in plant which lead not only to growth promotion but also protection from pathogenic stress conditions in rice. The two most promising strains, P. fluorescens PF-08 and T. harzianum UBSTH-501 selected on the basis of in planta evaluation, when applied individually or in combination, significantly enhanced the accumulation of defence-related biomolecules, enzymes and exhibited biocontrol potential against R. solani. A modified/newly developed delivery system was applied for the first time in the experiments involving inoculation of plants with both bioagents, viz. P. fluorescens PF-08 and T. harzianum UBSTH-501. Results suggested that application of P. fluorescens PF-08 and T. harzianum UBSTH-501 alone or in combination, not only helps in control of the disease but also increases plant growth along with reduction in application of toxic chemical pesticides. PMID- 27664751 TI - An autophagy gene, HoATG5, is involved in sporulation, cell wall integrity and infection of wounded barley leaves. AB - The endophytic fungus Harpophora oryzae is a beneficial endosymbiont isolated from wild rice. H. oryzae can not only promote rice growth and biomass accumulation but also protect rice roots from invasion by its close relative Magnaporthe oryzae. Autophagy is a highly evolutionary conserved process from lower to higher eukaryotic organisms, and is involved in the maintenance of normal cell differentiation and development. In this study, we isolated a gene (HoATG5) which encodes an essential protein required for autophagy from the beneficial endophyte fungus H. oryzae. Using targeted gene replacement, a DeltaHoATG5 mutant was generated and used to investigate the biological functions of autophagy in H. oryzae. We found that the autophagic process was blocked in the HoATG5 deletion mutant. The mutant showed increased vegetative growth and sporulation, and was sensitive to nutrient starvation. The DeltaHoATG5 mutant lost its ability to penetrate and infect the wounded barley leaves. These results provide new knowledge to elaborate the molecular machinery of autophagy in endophytic fungi. PMID- 27664752 TI - Corrigendum to "Evaluation of acrylamide-removing properties of two Lactobacillus strains under simulated gastrointestinal conditions using a dynamic system" [Microbiol. Res. 190 (September) (2016) 19-26]. PMID- 27664753 TI - Next-Generation Sequencing in Cancer Diagnostics. AB - This commentary highlights the article by Misyura et al that underscores the use of next-generation sequencing platforms for detection and verification of somatic variants. PMID- 27664755 TI - T-cell immunometabolism against cancer. AB - T cells play critical roles in host defenses against cancer. External signals prompt activation of naive T cells, triggering modulation of their immune functions. Emerging evidence reveals that distinct metabolic changes impact the immune functions of naive and effector T cells, including CD4+ and CD8+ T cells. Since T cells appear to be key players in tumor progression, it is important to elucidate whether and how T-cell metabolic reprogramming might alter their impact on cancer progression. Here we briefly review the available knowledge regarding T cells in relation to cancer, focusing on the metabolic reprogramming of T cells and how this influences tumor progression. Emerging insights in this field are improving our understanding of the functional role of T-cell metabolic reprogramming in cancer. Further research could provide a critical foundation for new treatments targeting cancer metabolism. PMID- 27664756 TI - Groundwater vulnerability indices conditioned by Supervised Intelligence Committee Machine (SICM). AB - This research presents a Supervised Intelligent Committee Machine (SICM) model to assess groundwater vulnerability indices of an aquifer. SICM uses Artificial Neural Networks (ANN) to overarch three Artificial Intelligence (AI) models: Support Vector Machine (SVM), Neuro-Fuzzy (NF) and Gene Expression Programming (GEP). Each model uses the DRASTIC index, the acronym of 7 geological, hydrological and hydrogeological parameters, which collectively represents intrinsic (or natural) vulnerability and gives a sense of contaminants, such as nitrate-N, penetrating aquifers from the surface. These models are trained to modify or condition their DRASTIC index values by measured nitrate-N concentration. The three AI-techniques often perform similarly but have differences as well and therefore SICM exploits the situation to improve the modeled values by producing a hybrid modeling results through selecting better performing SVM, NF and GEP components. The models of the study area at Ardabil aquifer show that the vulnerability indices by the DRASTIC framework produces sharp fronts but AI models smoothen the fronts and reflect a better correlation with observed nitrate values; SICM improves on the performances of three AI models and cope well with heterogeneity and uncertain parameters. PMID- 27664754 TI - The EP1/EP3 receptor agonist 17-pt-PGE2 acts as an EP4 receptor agonist on endothelial barrier function and in a model of LPS-induced pulmonary inflammation. AB - Endothelial dysfunction is a hallmark of inflammatory conditions. We recently demonstrated that prostaglandin (PG)E2 enhances the resistance of pulmonary endothelium in vitro and counteracts lipopolysaccharide (LPS)-induced pulmonary inflammation in vivo via EP4 receptors. The aim of this study was to investigate the role of the EP1/EP3 receptor agonist 17-phenyl-trinor-(pt)-PGE2 on acute lung inflammation in a mouse model. In LPS-induced pulmonary inflammation in mice, 17 pt-PGE2 reduced neutrophil infiltration and inhibited vascular leakage. These effects were unaltered by an EP1 antagonist, but reversed by EP4 receptor antagonists. 17-pt-PGE2 increased the resistance of pulmonary microvascular endothelial cells and prevented thrombin-induced disruption of endothelial junctions. Again, these effects were not mediated via EP1 or EP3 but through activation of the EP4 receptor, as demonstrated by the lack of effect of more selective EP1 and EP3 receptor agonists, prevention of these effects by EP4 antagonists and EP4 receptor knock-down by siRNA. In contrast, the aggregation enhancing effect of 17-pt-PGE2 in human platelets was mediated via EP3 receptors. Our results demonstrate that 17-pt-PGE2 enhances the endothelial barrier in vitro on pulmonary microvascular endothelial cells, and accordingly ameliorates the recruitment of neutrophils, via EP4 receptors in vivo. This suggests a beneficial effect of 17-pt-PGE2 on pulmonary inflammatory diseases. PMID- 27664757 TI - An improved method for estimating GHG emissions from onshore oil and gas exploration and development in China. AB - Greenhouse gas (GHG) emissions from oil and gas exploration and development are major contributors to emission inventories in oil and natural gas (ONG) systems. For the developing countries, including China, studies of this aspect of the industry, being at an early stage, lack a unified method of calculation, and this leads to varied projections of national emissions. In this paper, progress is reported on direct measurement of CH4 and CO2 emissions along the oil and gas value chain, for four oil and gas fields. An improved calculation method (classification calculation method), which considers the production status of each type of oil and gas field in China, is proposed for the first time in this study. Based on in situ measurement, it is used to estimate the national CH4 and CO2 emissions from the process of petroleum exploration and development. The results showed that CH4 and CO2 emissions in 2013 were 73.29*104 and 20.32*104tonnes, respectively (in CO2 equivalent: 1559.36*104tonnes). Compared with the results (731.52*104tonnes of CH4, 1031.55*104tonnes of CO2, 16,393.48*104tonnes of CO2 equivalent) in 2013 determined by the Tier 1 method of the Intergovernmental Panel on Climate Change (IPCC), the carbon emissions from field measurement method were much lower than that of IPCC method, which indicated that carbon emissions of ONG systems in China were severely overrated by IPCC. Hence, the GHG emission results reported herein could fundamentally improve the knowledge and understanding of GHG emissions from ONG exploration and development in China. PMID- 27664758 TI - Study of the water transportation characteristics of marsh saline soil in the Yellow River Delta. AB - One-dimensional soil column water infiltration and capillary adsorption water tests were conducted in the laboratory to study the water transportation characteristics of marsh saline soil in the Yellow River Delta, providing a theoretical basis for the improvement, utilization and conservation of marsh saline soil. The results indicated the following: (1) For soils with different vegetation covers, the cumulative infiltration capacity increased with the depth of the soil layers. The initial infiltration rate of soils covered by Suaeda and Tamarix chinensis increased with depth of the soil layers, but that of bare soil decreased with soil depth. (2) The initial rate of capillary rise of soils with different vegetation covers showed an increasing trend from the surface toward the deeper layers, but this pattern with respect to soil depth was relatively weak. (3) The initial rates of capillary rise were lower than the initial infiltration rates, but infiltration rate decreased more rapidly than capillary water adsorption rate. (4) The two-parameter Kostiakov model can very well simulate the changes in the infiltration and capillary rise rates of wetland saline soil. The model simulated the capillary rise rate better than it simulated the infiltration rate. (5) There were strong linear relationships between accumulative infiltration capacity, wetting front, accumulative capillary adsorbed water volume and capillary height. PMID- 27664759 TI - Risk assessment of airborne pesticides in a Mediterranean region of Spain. AB - A risk assessment strategy based on the quantitative target analysis and semi quantitative retrospective screening determination of pesticides in PM10 has been developed. The proposed methodology was applied to 345 real samples from nine stations of a Mediterranean area in Spain, and the risk was assessed for adult, children and infants. Forty pesticides were detected with average concentrations ranging from 8 to 30,000pgm-3. Each station showed its specific pesticide profile, which is linked to the different types of crops around each station. For adults, children and infants the estimated chronic inhalation risk, expressed as Hazard Quotient (HQ), was <1 for all pesticides. The cumulative exposure for organophosphates, neonicotinoids, benzimidazoles, carbamates, micro-organism and triazoles pesticides (HI, Hazard Index) were <1 for the three groups of populations assessed. For infants, the cancer risk estimated for the detected pesticides classified as possible and potential carcinogens were lower than 1.0 E 06, except for carbendazim and hexythiazox. PMID- 27664760 TI - Effects of organic amendment on soil aggregation and microbial community composition during drying-rewetting alternation. AB - The alternation of drying and rewetting events could dramatically affect the biological and structural properties of soil and consequently influence nutrient transformation. To examine whether organic amendments could improve the resistance and resilience of microbial function (extracellular enzyme activities), community composition (phospholipid fatty acids), and soil structure to drying-rewetting alternation, cropland soils with or without wheat-straw amendment were allowed to desiccate in a microcosm for two months, followed by moist incubation for five weeks, and continuously moist treatments were maintained at 50% water holding capacity during the entire period, as a control treatment. Straw amendment increased microbial biomass, extracellular enzyme activities, the relative abundance of fungal groups, dissolved organic carbon, and proportion of large macroaggregates (>2000MUm), but decreased mineral nitrogen and available phosphorus. The drying-rewetting treatment increased microbial biomass carbon and beta-glucosidase activities by 10% and 13% in straw amended soils, respectively, but not in unamended soils, and decreased the urease and alkaline phosphomonoesterase activities by >15% in unamended soils, but not in amended soils. The contents of fungi, actinomycetes, Pseudomonas spp., and Bacillus spp. decreased with drying, and more so with the subsequent rewetting, but recovered by the end of the experiment. The drying-rewetting treatment caused a decrease in the nitrate content in both soils (>10%) and an increase in the macroaggregates of straw-amended soils (~8%). These results indicated that improved soil aggregation, as a result of straw amendment, protected microbial communities from drought stress and that nutrient acquisition promoted the post rewetting colonization of heterotrophic communities characterized by hydrolase production, which consequently facilitated aggregate re-formation. Thus, straw amendment positively contributed to aggregate turnover and to both microbial and enzymatic responses to drying-rewetting events, which suggests that straw amendment is favorable to maintain soil function under conditions of increasing rainfall variability. PMID- 27664761 TI - Solar ultraviolet doses and vitamin D in a northern mid-latitude. AB - Solar ultraviolet (UV) radiation is one of the most important factors in the development of skin cancer in human, solar erythema and skin aging. Nevertheless, numerous studies have shown the benefits of UV solar radiation in moderate doses, such as the reduction of blood pressure and mental health, treatment of various diseases, and the synthesis of vitamin D in the skin. This paper analyses data from solar ultraviolet erythemal (UVER) irradiance in W/m2 measured in a northern mid-latitude as Valencia (Spain) for the period 2003-2010. To estimate effective solar UV radiation in the production of vitamin D (UVD) we used the relationship proposed by McKenzie et al. (2009). It was obtained for one month for each season the minimum exposure time needed around solar noon and at 9 UTC and 15 UTC (Coordinated Universal Time) to obtain the recommended daily dose of 1000IU. Also, it has been calculated time for erythema induction around solar noon for the same months. The median UVER daily dose during the summer months was 4000J/m2day, and 700J/m2day in winter. With regard to UVD, the median UVD daily dose in summer season was 7700J/m2day, and in winter it was 1000J/m2day. Around noon in January it takes more than two hours of solar exposure to obtain the recommended daily dose of vitamin D, whereas the rest of the year range between 7min on July and 31min on October. For the same months around noon, exposure times to produce erythema were obtained, these being of higher value to the previous. The results show that it is difficult to obtain the recommended vitamin D doses in winter in a northern mid-latitude, as the human body is almost entirely covered in this season. PMID- 27664762 TI - Impact of a thermokarst lake on the soil hydrological properties in permafrost regions of the Qinghai-Tibet Plateau, China. AB - The formation of thermokarst lakes can degrade alpine meadow ecosystems through changes in soil water and heat properties, which might have an effect on the regional surface water and groundwater processes. In this study, a typical thermokarst lake was selected in the Qinghai-Tibet Plateau (QTP), and the ecological index (SL) was used to divide the affected areas into extremely affected, severely affected, medium-affected, lightly affected, and non-affected areas, and soil hydrological properties, including saturated hydraulic conductivity and soil water-holding capacity, were investigated. The results showed that the formation of a thermokarst lake can lead to the degradation of alpine meadows, accompanied by a change in the soil physiochemical and hydrological properties. Specifically, the soil structure turned towards loose soil and the soil nutrients decreased from non-affected areas to severely affected areas, but the soil organic matter and available potassium increased slightly in the extremely affected areas. Soil saturated hydraulic conductivity showed a 1.7- to 4.1-fold increase in the lake-surrounding areas, and the highest value (401.9cmd-1) was detected in the severely affected area. Soil water-holding capacity decreased gradually during the transition from the non-affected areas to the severely affected areas, but it increased slightly in the extremely affected areas. The principal component analysis showed that the plant biomass was vital to the changes in soil hydrological properties. Thus, the vegetation might serve as a link between the thermokarst lake and soil hydrological properties. In this particular case, it was concluded that the thermokarst lake adversely affected the regional hydrological services in the alpine ecosystem. These results would be useful for describing appropriate hydraulic parameters with the purpose of modeling soil water transportation more accurately in the Qinghai-Tibet Plateau. PMID- 27664763 TI - Impact of agricultural practices on groundwater quality in intensive irrigated area of Chtouka-Massa, Morocco. AB - The Plio-Quaternary aquifer of Chtouka is located in Southwestern of Morocco. The intensive agricultural activity in Chtouka basin requires the mobilization of 94% of fresh water resources for irrigation. This overexploitation, along with the succession of drought years, sea water intrusion and various sources of pollution, affected the quality and availability of groundwater resources. Several sampling campaigns were carried out in different sites of the study area in order to investigate the spatial variation of groundwater quality. The temporal evolution of groundwater level shows that the water table was subjected to a gradual decline during the last decade, indicating an intensive exploitation mainly in irrigated areas. In the Southern part around Belfaa and the irrigated area along Massa River, nitrate concentrations exceed 50mg/L, which is the threshold set by the World Health Organization, while in the northern part around Biougra and Ait Amira, the nitrate concentration is mostly below 50mg/L indicating a relative good groundwater quality. This finding can be explained by the improvement of agricultural practices, particularly the conversion of flood and sprinkler irrigation to drip irrigation (80% of the total irrigated area) in most of the developed farms in this part of the study area. Moreover, the exploitation of groundwater from the deep aquifer, due to the increasing water demand in the region, can also explain the low chemical concentrations since the deep aquifer is not affected by anthropogenic pollutants or marine intrusion. Stable isotopes (18O and 2H) highlight the different origins of groundwater, indicating the complexity of the aquifer system path flows, which is attributable to the intensive exploitation and irrigation water return. PMID- 27664764 TI - Effects of charge and surface defects of multi-walled carbon nanotubes on the disruption of model cell membranes. AB - The direct contact between multi-walled carbon nanotubes (MWCNTs) and cell membranes causes membrane disruption, potentially leading to cytotoxicity. However, the role of electrostatic forces and MWCNT properties is still open to debate. In this study, the influences of charge and MWCNT surface defects on membrane disruption were investigated by microscopy and a quartz crystal microbalance with dissipation monitoring (QCM-D). Positively/negatively charged giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) were made as model cell membranes. Negatively charged MWCNTs disrupted the GUVs containing positively charged lipids, which confirmed the electrostatically mediated interaction. However, the mass loss was detected from the negatively charged SLBs after MWCNT exposure, which suggests the extraction of phospholipids. The defect degree of MWCNTs correlated with their adhesion amount on the membranes. Both the oxygenated functional groups and unoxidized dangling carbon bonds were active sites for MWCNT-membrane interactions. The MWCNTs were observed to be engulfed inside the GUVs. The results clearly demonstrate that phospholipid extraction by MWCNTs could occur in electrostatically repulsive conditions, and MWCNT defects were active binding sites whether or not they were oxygenated. Our findings should be helpful in the design and safe applications of carbon nanomaterials. PMID- 27664765 TI - Categorizing chlordecone potential degradation products to explore their environmental fate. AB - Chlordecone (C10Cl10O; CAS number 143-50-0) has been used extensively as an organochlorine insecticide but is nowadays banned and listed on annex A in The Stockholm Convention on Persistent Organic Pollutants (POPs). Although experimental evidences of biodegradation of this compound are scarce, several dechlorination products have been proposed by Dolfing et al. (2012) using Gibbs free energy calculations to explore different potential transformation routes. We here present the results of an in silico classification (TyPol - Typology of Pollutants) of chlordecone transformation products (TPs) based on statistical analyses combining several environmental endpoints and structural molecular descriptors. Starting from the list of putative chlordecone TPs and considering available data on degradation routes of other organochlorine compounds, we used different clustering strategies to explore the potential environmental behaviour of putative chlordecone TPs from the knowledge on their molecular descriptors. The method offers the possibility to focus on TPs present in different classes and to infer their environmental fate. Thus, we have deduced some hypothetical trends for the environmental behaviour of TPs of chlordecone assuming that TPs, which were clustered away from chlordecone, would have different environmental fate and ecotoxicological impact compared to chlordecone. Our findings suggest that mono- and di-hydrochlordecone, which are TPs of chlordecone often found in contaminated soils, may have similar environmental behaviour in terms of persistence. PMID- 27664766 TI - Mitigation of saltwater intrusion by 'integrated fresh-keeper' wells combined with high recovery reverse osmosis. AB - Most countermeasures to mitigate saltwater intrusion in coastal, karstic or fractured aquifers are hindered by anisotropy, high transmissivities and complex dynamics. A coupled strategy is introduced here as a localized remedy to protect shallow freshwater reserves while utilizing the deeper intercepted brackish water. It is a double sourcing application where fresh-keeper wells are installed at the bottom of a deepened borehole of selected salinized wells, and then supported by high recovery RO desalination. The RO design has <1kWh/m3 energy consumption, and up to 96% recovery in addition to low scaling propensity without use of any anti-scalant. A feasibility study is presented as an example for a salinizing, brackish well (TDS ~1600mg/L) in the Damour coastal aquifer in Lebanon. The concept is expected to produce ca. 1000m3/d of freshwater from this well by pumping 250m3/d of fresh groundwater from the top well screen and 800m3/d of brackish groundwater (to be later desalinized) from the fresh-keeper well screen below. Cost analysis shows that the capital cost could be returned back in 1 to 4years depending on the choice of produced water (bottled or tap) and available market. As an alternative, water from the RO plant could be blended with lower quality water, for instance untreated brackish groundwater (if unpolluted), to supply 3 more volumes for domestic use. The usage of brackish groundwater from integrated fresh-keeper wells thus serves 3 purposes: production of high quality drinking water, financial gain and mitigation of water stress by overpumping. PMID- 27664767 TI - SIMSWASTE-AD - A modelling framework for the environmental assessment of agricultural waste management strategies: Anaerobic digestion. AB - On-farm anaerobic digestion (AD) has been promoted due to its improved environmental performance, which is based on a number of life cycle assessments (LCA). However, the influence of site-specific conditions and practices on AD performance is rarely captured in LCA studies and the effects on C and N cycles are often overlooked. In this paper, a new model for AD (SIMSWASTE-AD) is described in full and tested against a selection of available measured data. Good agreement between modelled and measured values was obtained, reflecting the model capability to predict biogas production (r2=0.84) and N mineralization (r2=0.85) under a range of substrate mixtures and operational conditions. SIMSWASTE-AD was also used to simulate C and N flows and GHG emissions for a set of scenarios exploring different AD technology levels, feedstock mixtures and climate conditions. The importance of post-digestion emissions and its relationship with the AD performance have been stressed as crucial factors to reduce the net GHG emissions (-75%) but also to enhance digestate fertilizer potential (15%). Gas tight digestate storage with residual biogas collection is highly recommended (especially in temperate to warm climates), as well as those operational conditions that can improve the process efficiency on degrading VS (e.g. thermophilic range, longer hydraulic retention time). Beyond the effects on the manure management stage, SIMSWASTE-AD also aims to help account for potential effects of AD on other stages by providing the C and nutrient flows. While primarily designed to be applied within the SIMSDAIRY modelling framework, it can also interact with other models implemented in integrated approaches. Such system scope assessments are essential for stakeholders and policy makers in order to develop effective strategies for reducing GHG emissions and environmental issues in the agriculture sector. PMID- 27664768 TI - Gene expression analysis during the induction and patterning of the conjunctival papillae in the chick embryonic eye. AB - The induction and patterning of the conjunctival papillae (i.e. epithelial thickenings of the conjunctiva required for the induction of the underlying, neural crest-derived scleral ossicles) is complex. It takes place over a period of two days and follows a defined spatiotemporal sequence. In this study, we investigated the spatial and temporal expression pattern of four genes over seven morphological stages of development of these papillae. We show that beta-catenin is expressed during the pre-patterning of the epithelium prior to papilla induction and second that beta-catenin, Ednrb and Inhba are expressed during the induction and patterning of the conjunctival papillae. Furthermore, we identified two genes, beta-catenin and Prox1, that may be involved in the induction of the underlying scleral bones. These data provide an excellent baseline for future studies, setting the stage for functional studies aimed at examining the role of these genes in the patterning of the scleral ossicle system. This study also outlines the similarities between the conjunctival papillae and other placodes and may provide insights into the evolution and development of the conjunctival papillae. PMID- 27664769 TI - SYP-5, a novel HIF-1 inhibitor, suppresses tumor cells invasion and angiogenesis. AB - Hypoxia-inducible factor-1 (HIF-1) plays an essential role in carcinogenesis. The overexpression of HIF-1 induced by hypoxia is closely associated with metastasis, poor prognosis and high mortality. In this study, a novel HIF-1 inhibitor SYP-5 was first observed by the luciferase reporter assay. Western blots results showed SYP-5 inhibited hypoxia-induced upregulation of HIF-1. Moreover, the proteins of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 that are targets of HIF-1, were down-regulated by SYP-5. Furthermore, in the tube formation assay, SYP-5 suppressed angiogenesis induced by hypoxia and VEGF in vitro. Additionally, using Transwell and RTCA assays, we found that SYP-5 also retarded the Hep3B and Bcap37 cells migration and invasion induced by hypoxia and FBS. Last, we also detected the upstream pathways related to HIF-1 and found both PI3K/AKT and MAPK/ERK were involved in the SYP-5 mediated invasive inhibition of Bcap37 cells. These results indicates that SYP-5 inhibits tumor cell migration and invasion, as well as tumor angiogenesis, which are mediated by suppressing PI3K/AKT- and MAPK/ERK-dependent HIF-1 pathway. It suggests that SYP-5 might be a potential HIF-1 inhibitor as an anticancer agent. PMID- 27664770 TI - In vivo cardiac nano-imaging: A new technology for high-precision analyses of sarcomere dynamics in the heart. AB - The cardiac pump function is a result of a rise in intracellular Ca2+ and the ensuing sarcomeric contractions [i.e., excitation-contraction (EC) coupling] in myocytes in various locations of the heart. In order to elucidate the heart's mechanical properties under various settings, cardiac imaging is widely performed in today's clinical as well as experimental cardiology by using echocardiogram, magnetic resonance imaging and computed tomography. However, because these common techniques detect local myocardial movements at a spatial resolution of ~100 MUm, our knowledge on the sub-cellular mechanisms of the physiology and pathophysiology of the heart in vivo is limited. This is because (1) EC coupling occurs in the MUm partition in a myocyte and (2) cardiac sarcomeres generate active force upon a length change of ~100 nm on a beat-to-beat basis. Recent advances in optical technologies have enabled measurements of intracellular Ca2+ dynamics and sarcomere length displacements at high spatial and temporal resolution in the beating heart of living rodents. Future studies with these technologies are warranted to open a new era in cardiac research. PMID- 27664772 TI - Regenerative peripheral neuropathic pain: novel pathological pain, new therapeutic dimension. AB - After peripheral nerve damage, injured or stressed primary sensory neurons (PSNs) transmitting pathological pain (pathopain) sensitize central nervous system (CNS) neural circuits and determine behavioral phenotypes of peripheral neuropathic pain (PNP). Therefore, phenotypic profiling of pathopain-transmitting PSNs is vital for probing and discovering PNP conditions. Following peripheral nerve injuries (PNIs), PNP might be potentially transmitted by distinct classes of damaged or stressed PSNs, such as axotomized PSNs without regeneration (axotomy non-regenerative neurons), axotomized PSNs with accurate regeneration (axotomy regenerative neurons), and spared intact PSNs adjacent to axotomized neurons (axotomy-spared neurons). Both axotomy-non-regenerative neurons and axotomy spared neurons have been definitely shown to participate in specific PNP transmission. However, whether axotomy-regenerative neurons could transmit PNP with unique features has remained unclear. Recent studies in rodent models of axonotmesis have clearly demonstrated that axotomy-regenerative neurons alone transmit persistent pathological pain with unique behavioral phenotypes. In this review, we exclusively review this novel category of PNP, reasonably term it 'regenerative peripheral neuropathic pain', and finally discuss its potential clinical significance as a new therapeutic dimension for PNIs beyond nerve regeneration. PMID- 27664773 TI - Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4 benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice. AB - BACKGROUND: 5-HT3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT3 receptor antagonist, 6g (4-benzylpiperazin-1-yl)(3 methoxyquinoxalin-2-yl) methanone, which exhibited good log P (3.08) and pA2 (7.5) values was screened for its anxiolytic property in lipopolysaccharide (LPS) induced anxiety models. METHODS: LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined. RESULTS: The results showed that LPS induced anxiety-like symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPS induced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain. CONCLUSIONS: Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain. PMID- 27664771 TI - Contested moral landscapes: Negotiating breastfeeding stigma in breastmilk sharing, nighttime breastfeeding, and long-term breastfeeding in the U.S. and the U.K. AB - Recent public health breastfeeding promotion efforts have galvanized media debates about breastfeeding in wealthy, Euro-American settings. A growing body of research demonstrates that while breastfeeding is increasingly viewed as important for health, mothers continue to face significant structural and cultural barriers. Concerns have been raised about the moralizing aspects of breastfeeding promotion and its detrimental effects on those who do not breastfeed. Far less, however, is known about the moral experiences of those who pursue breastfeeding. This study draws together research on breastmilk sharing (2012-2016) and nighttime breastfeeding from the U.S. (2006-2009), and long-term breastfeeding from the U.K. (2008-2009) from three ethnographic projects to address this gap. Comparative analysis of these cases reveals that while breastfeeding is considered ideal infant nutrition, aspects of its practice continue to evoke physical and moral danger, even when these practices are implemented to facilitate breastfeeding. Breastmilk sharing to maintain exclusive breastmilk feeding, nighttime breastfeeding and bedsharing to facilitate breastfeeding, and breastfeeding beyond the accepted duration are considered unnecessary, unhealthy, harmful or even deadly. The sexual connotations of breastfeeding enhance the morally threatening qualities of these practices. The cessation of these "problematic" breastfeeding practices and their replacement with formula-feeding or other foods is viewed as a way to restore the normative social and moral order. Mothers manage the stigmatization of these breastfeeding practices through secrecy and avoidance of health professionals and others who might judge them, often leading to social isolation. Our findings highlight the divide between perceptions of the ideal of breastfeeding and its actual practice and point to the contested moral status of breastfeeding in the U.S. and the U.K. Further comparative ethnographic research is needed to illuminate the lived social and moral experiences of breastfeeding, and inform initiatives to normalize and support its practice without stigmatizing parents who do not breastfeed. PMID- 27664774 TI - Stoichiometry determination of macromolecular membrane protein complexes. AB - Gaining knowledge of the structural makeup of protein complexes is critical to advance our understanding of their formation and functions. This task is particularly challenging for transmembrane protein complexes, and grows ever more imposing with increasing size of these large macromolecular structures. The last 10 years have seen a steep increase in solved high-resolution membrane protein structures due to both new and improved methods in the field, but still most structures of large transmembrane complexes remain elusive. An important first step towards the structure elucidation of these difficult complexes is the determination of their stoichiometry, which we discuss in this review. Knowing the stoichiometry of complex components not only answers unresolved structural questions and is relevant for understanding the molecular mechanisms of macromolecular machines but also supports further attempts to obtain high resolution structures by providing constraints for structure calculations. PMID- 27664776 TI - Consensus numbering system for the rifampicin resistance-associated rpoB gene mutations in pathogenic mycobacteria. AB - The rpoB gene codes for the RNA polymerase beta subunit, which is the target of rifampicin, an essential drug in the treatment of tuberculosis and other mycobacterial infections. This gene is present in all bacteria, but its length and nucleotide sequence vary between bacterial species, including mycobacteria. Mutations in the rpoB gene alter the structure of this protein and cause drug resistance. To describe the resistance-associated mutations, the scientific and medical communities have been using, since 1993, a numbering system based on the Escherichia coli sequence annotation. Using E. coli reference for describing mutations in mycobacteria leads to misunderstandings, particularly with the increasing use of whole genome sequencing, which brought an alternative numbering system based on the Mycobacterium tuberculosis rpoB sequence. We propose using a consensus numbering system for the reporting of resistance mutations based on the reference genomes from the species interrogated (such as strain H37Rv for M. tuberculosis). This manuscript provides the necessary figures and tables allowing researchers, microbiologists and clinicians to easily convert other annotation systems into one common language. PMID- 27664777 TI - Methanobrevibacter smithii and Bacteroides thetaiotaomicron cultivated from a chronic paravertebral muscle abscess. PMID- 27664778 TI - Detection of parvovirus B19 DNA in blood: Viruses or DNA remnants? AB - BACKGROUND: Parvovirus B19 (B19V) DNA can be detected in blood over a long period after acute infection. Several reports associate the presence of B19V DNA with disease, irrespective of timing of the initial B19V infection. OBJECTIVES: This study aims to analyze the properties of B19V DNA in blood, differentiating between bare, non-infectious strands of DNA and B19V DNA in viable virions. STUDY DESIGN: Ten blood donors with asymptomatic acute B19V infection were followed and sampled up to 22 months after infection. The samples were treated with and without an endonuclease and tested for B19V DNA, to distinguish between DNA in virions and naked DNA. RESULTS: In the acute phase of infection, high levels of B19V DNA were detected, concurrent with B19V IgM antibodies. B19V DNA apparently was encapsidated, as indicated by resistance to endonuclease degradation. Subsequently, B19V DNA remained detectable for more than one year in all donors at low levels (<105 IU/mL). Approximately 150days after infection B19V DNA became degradable by an endonuclease, indicating that this concerned naked DNA. In some donors a second endonuclease-resistant peak occurred. DISCUSSION: Detection of B19V DNA in blood by PCR does not necessarily imply that B19V replication takes place and that infectious B19V virions are present. We propose that remnant B19V DNA strands can be released from tissues without active replication. This finding urges to reconsider an assumed role of B19V infection mainly based on B19V DNA detection in blood, a much debated subject in clinical syndromes such as myocarditis and arthritis. PMID- 27664775 TI - The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. AB - The proton-coupled folate transporter (PCFT-SLC46A1) is the mechanism by which folates are absorbed across the brush-border membrane of the small intestine. The transporter is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of PCFT function, as occurs in the autosomal recessive disorder "hereditary folate malabsorption" (HFM), results in a syndrome characterized by severe systemic and cerebral folate deficiency. Folate-receptor alpha (FRalpha) is expressed in the choroid plexus, and loss of function of this protein, as also occurs in an autosomal recessive disorder, results solely in "cerebral folate deficiency" (CFD), the designation for this disorder. This paper reviews the current understanding of the functional and structural properties and regulation of PCFT, an electrogenic proton symporter, and contrasts PCFT properties with those of the reduced folate carrier (RFC), an organic anion antiporter, that is the major route of folate transport to systemic tissues. The clinical characteristics of HFM and its treatment, based upon the thirty-seven known cases with the clinical syndrome, of which thirty have been verified by genotype, are presented. The ways in which PCFT and FRalpha might interact at the level of the choroid plexus such that each is required for folate transport from blood to cerebrospinal fluid are considered along with the different clinical presentations of HFM and CFD. PMID- 27664779 TI - Discourse comprehension in L2: Making sense of what is not explicitly said. AB - Using ERPs, we tested whether L2 speakers can integrate multiple sources of information (e.g., semantic, pragmatic information) during discourse comprehension. We presented native speakers and L2 speakers with three-sentence scenarios in which the final sentence was highly causally related, intermediately related, or causally unrelated to its context; its interpretation therefore required simple or complex inferences. Native speakers revealed a gradual N400 like effect, larger in the causally unrelated condition than in the highly related condition, and falling in-between in the intermediately related condition, replicating previous results. In the crucial intermediately related condition, L2 speakers behaved like native speakers, however, showing extra processing in a later time-window. Overall, the results show that, when reading, L2 speakers are able to process information from the local context and prior information (e.g., world knowledge) to build global coherence, suggesting that they process different sources of information to make inferences online during discourse comprehension, like native speakers. PMID- 27664780 TI - Fine structure of antennal sensilla of the spittlebug Philaenus spumarius L. (Insecta: Hemiptera: Aphrophoridae). I. Chemoreceptors and thermo /hygroreceptors. AB - The meadow spittlebug, Philaenus spumarius (L.) (Hemiptera: Cercopoidea: Aphrophoridae), is a polyphagous species that transmits Xylella fastidiosa, a bacterium associated with "Olive Quick Decline Syndrome" in Southern Italy. In this study, the morphology and the ultrastructure of the antennal sensilla of P. spumarius were investigated. The antennae consist of three segments: a basal scape, a pedicel and a flagellum composed of a basal enlargement (ampulla) and a long segment (filament). The pedicel bears a single campaniform sensillum while the ampulla houses twelve coeloconic sensilla and three large basiconic sensilla. These latter sensilla show a smooth multiporous external cuticular wall and a total number of 27 sensory neurons per sensillum. The coeloconic sensilla belong to two morphologically distinct types: double-walled and single-walled sensilla. The sensory peg of the double-walled sensilla is smooth at the base and distally has a grooved cuticular surface with pores organized in spoke channels between each ridge. Three sensory neurons enter the lumen while at the basal level, before entering the peg, a fourth sensory neuron is found. The single-walled sensilla show an aporous thick cuticular wall and two sensory neurons entering the sensillar lumen, with a third neuron ending at the sensillum base. PMID- 27664781 TI - Distribution of the obligate endosymbiont Blochmannia floridanus and expression analysis of putative immune genes in ovaries of the carpenter ant Camponotus floridanus. AB - The bacterial endosymbiont Blochmannia floridanus of the carpenter ant Camponotus floridanus contributes to its hosts' ontogeny via nutritional upgrading during metamorphosis. This primary endosymbiosis is essential for both partners and vertical transmission of the endosymbionts is guaranteed by bacterial infestation of oocytes. Here we present a detailed analysis of the presence and localisation of B. floridanus in the ants' ovaries obtained by FISH and TEM analyses. The most apical part of the germarium harbouring germ-line stem cells (GSCs) is not infected by the bacteria. The bacteria are detectable for the first time in lower parts of the germarium when cystocytes undergo the 4th and 5th division and B. floridanus infects somatic cells lying under the basal lamina surrounding the ovarioles. With the beginning of cystocyte differentiation, the endosymbionts are exclusively transported from follicle cells into the growing oocytes. This infestation of the oocytes by bacteria very likely involves exocytosis endocytosis processes between follicle cells and the oocytes. Nurse cells were never found to harbour the endosymbionts. Furthermore we present first gene expression data in C. floridanus ovaries. These data indicate a modulation of immune gene expression which may facilitate tolerance towards the endosymbionts and thus may contribute to their transovarial transmission. PMID- 27664789 TI - Microbial dynamics of indicator microorganisms on fresh tomatoes in the supply chain from Mexico to the USA. AB - Quality and safety of fresh produce are important to public health and maintaining commerce between Mexico and USA. While preventive practices can reduce risks of contamination and are generally successful, the variable environment of the supply chain of fresh produce can be suitable for introduction or proliferation of pathogenic microorganisms. As routine surveillance of these pathogens is not practical, indicator microorganisms are used to assess the sanitary conditions of production and handling environments. An opportunity exists to use indicators on fresh produce to measure how handling and transport from field to market may affect microbial populations that contribute to their quality or safety. The objective was to quantify indicator microorganisms on tomatoes sampled along the supply chain during the harvest year, in order to observe the levels and changes of populations at different locations. Roma tomatoes (n=475) were taken from the same lots (n=28) at four locations of the postharvest supply chain over five months: at arrival to and departure from the packinghouse in Mexico, at the distribution center in Texas, and at retail in USA. Samples were analyzed individually for four microbial populations: aerobic plate count (APC), total coliforms (TC), generic Escherichia coli, and yeasts and molds (YM). APC population differed (p<0.05) from 1.9+/-1.1, 1.7+/-1.1, 2.3+/-1.1 and 3.5+/-1.4logCFU/g at postharvest, packing, distribution center and supermarket, respectively. TC populations were <1logCFU/g at postharvest, increased at packing (0.7+/-1.0logCFU/g), decreased in distribution (0.4+/ 0.8logCFU/g) and increased in supermarkets (1.4+/-1.5logCFU/g). Generic E. coli was not identified from coliform populations in this supply chain. YM populations remained <1logCFU/g, with the exception of 1.1+/-1.3logCFU/g at supermarkets and tomatoes were not visibly spoiled. The levels reported from this pilot study demonstrated the dynamics within populations as influenced by time and conditions in one supply chain during a harvest year, while the large variances in some locations indicate opportunities for improvement. Overall, packinghouse and supermarket locations were identified as crucial points to control microbial safety risks. PMID- 27664782 TI - Changes in tarsal morphology and attachment ability to rough surfaces during ontogenesis in the beetle Gastrophysa viridula (Coleoptera, Chrysomelidae). AB - Insects live in a three-dimensional space, and need to be able to attach to different types of surfaces in a variety of environmental and behavioral contexts. Adult leaf beetles possess great attachment ability due to their hairy attachment pads. In contrast, their larvae depend on smooth pads to attach to the same host plant. We tested friction forces generated by larvae and adults of dock leaf beetles Gastrophysa viridula on different rough surfaces, and found that adults generate much higher attachment to various substrates than larvae, but are more susceptible to completely losing attachment ability on surfaces with "critical" roughness. Furthermore, sex-specific setal morphology has the effect that attachment forces of male adults are generally higher than those of females when adjusted for body weight. The results are discussed in the context of development, ecology, and changing behavioral strategies of successive life stages. PMID- 27664790 TI - Oligosaccharides containing an alpha-(1->2) (glucosyl/xylosyl)-fructosyl linkage as inducer molecules of trichothecene biosynthesis for Fusarium graminearum. AB - Fructo-oligosaccharides containing a sucrose unit are reported as carbon sources necessary for trichothecene production by Fusarium graminearum. Here we demonstrate that trichothecene production is induced when at least 100MUM sucrose is added to a culture medium containing 333mM glucose in a 24-well plate. When glucose, the main carbon source of the medium, was replaced with galactose, maltose, or sorbitol, the addition of 100MUM sucrose could no longer induce trichothecene production. However, replacing half the amount of each carbon source with glucose restored the trichothecene production-inducing activity of sucrose. Detailed investigations with media containing various concentrations of galactose and glucose as carbon sources suggested that operation of the galactose catabolic pathway for energy conservation affected trichothecene biosynthesis induction by sucrose. Trichothecene production was also induced by 100MUM of either raffinose or xylosucrose in axenic liquid culture medium containing glucose as the major carbon source. These results demonstrate that sucrose derivatives are not necessary as a carbon source for inducing trichothecene biosynthesis, and that the minimum structural requirement for sugars to function as trichothecene production-inducer molecules is to contain an alpha-(1->2) (glucosyl/xylosyl)-fructosyl linkage. PMID- 27664791 TI - Donepezil promotes differentiation of neural stem cells into mature oligodendrocytes at the expense of astrogenesis. AB - Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs). Donepezil treatment led to impaired self-renewal ability and increased apoptosis. These effects appeared to be mediated through the Akt/Bad signaling pathway. Using neurosphere differentiation analysis, we observed that donepezil leads to reduced numbers of astrocytes and increased numbers of oligodendrocytes and neurons. Consistent with this finding, mRNA and protein levels for the oligodendrocyte markers myelin-associated glycoprotein, 2', 3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), and myelin basic protein, as well as the neuronal marker beta-tubulin type III (Tuj1) were up-regulated. In contrast, the expression of the astrocyte marker glial fibrillary acidic protein (GFAP) was down-regulated by donepezil in a dose- and time-dependent manner. Moreover, donepezil increased oligodendrocyte differentiation, resulting in a reduction in the differentiation of NSCs into astrocytes, by suppressing the activation of signal transducer and activator of transcription 3 (STAT3), SMAD1/5/9, and the downstream target gene GFAP, even under astrocyte-inducing conditions. These results suggest that efficient differentiation of NSCs into oligodendrocytes by donepezil may indicate a novel therapeutic role for this drug in promoting repair in demyelinated lesions in addition to its role in preventing astrogenesis. PMID- 27664792 TI - Economic viability of Stratified Medicine concepts: An investor perspective on drivers and conditions that favour using Stratified Medicine approaches in a cost contained healthcare environment. AB - RATIONALE: Stratified Medicine (SM) is becoming a natural result of advances in biomedical science and a promising path for the innovation-based biopharmaceutical industry to create new investment opportunities. While the use of biomarkers to improve R&D efficiency and productivity is very much acknowledged by industry, much work remains to be done to understand the drivers and conditions that favour using a stratified approach to create economically viable products and to justify the investment in SM interventions as a stratification option. CONCEPT: In this paper we apply a decision analytical methodology to address the economic attractiveness of different SM development options in a cost-contained healthcare environment. For this purpose, a hypothetical business case in the oncology market has been developed considering four feasible development scenarios. CONCLUSIONS: The article outlines the effects of development time and time to peak sales as key economic value drivers influencing profitability of SM interventions under specific conditions. If regulatory and reimbursement challenges can be solved, decreasing development time and enhancing early market penetration would most directly improve the economic attractiveness of SM interventions. Appropriate tailoring of highly differentiated patient subgroups is the prerequisite to leverage potential efficiency gains in the R&D process. Also, offering a better targeted and hence ultimately more cost-effective therapy at reimbursable prices will facilitate time to market access and allow increasing market share gains within the targeted populations. PMID- 27664793 TI - The Celebration of 40 years of structural biology at Aarhus University as seen through the eyes of a translationalist. AB - Over the past 50 years, both Brian Clark and I have worked on tRNA, Brian more successfully than I. Our common interests have established collaborations and the training of Aarhus University students in my laboratory. As part of my rejuvenation plan, I have returned to Aarhus and participated in teaching a course in protein synthesis about every five years, beginning in 1990. It has been through this close contact with both Brian and the numerous faculty of the structural biology group that I have been able to witness and appreciate the great strides they have made, both in building a world class department and in the ground breaking discoveries that went with them. While much of the success of the Department of Molecular Biology and Genetics reflects the individual accomplishments of many, the growth of the department is largely a reflection of the dogged determination of Brian to develop one of the most modern and competitive departments in Denmark, if not in Europe (sort of reminds one of Winston Churchill). This retrospective highlights our parallel paths in tRNA and protein synthesis research and Brian's influence in establishing world renowned research in Aarhus. PMID- 27664794 TI - MC1R variants affect the expression of melanocortin and melanogenic genes and the association between melanocortin genes and coloration. AB - The melanocortin-1 receptor (MC1R) gene influences coloration by altering the expression of genes acting downstream in the melanin synthesis. MC1R belongs to the melanocortin system, a genetic network coding for the ligands that regulate MC1R and other melanocortin receptors controlling different physiological and behavioural traits. The impact of MC1R variants on these regulatory melanocortin genes was never considered, even though MC1R mutations could alter the influence of these genes on coloration (e.g. by decreasing MC1R response to melanocortin ligands). Using barn owl growing feathers, we investigated the differences between MC1R genotypes in the (co)expression of six melanocortin and nine melanogenic-related genes and in the association between melanocortin gene expression and phenotype (feather pheomelanin content). Compared to the MC1R rufous allele, responsible for reddish coloration, the white allele was not only associated with an expected lower expression of melanogenic-related genes (TYR, TYRP1, OCA2, SLC45A2, KIT, DCT) but also with a lower MC1R expression and a higher expression of ASIP, the MC1R antagonist. More importantly, the expression of PCSK2, responsible for the maturation of the MC1R agonist, alpha-melanocyte stimulating hormone, was positively related to pheomelanin content in MC1R white homozygotes but not in individuals carrying the MC1R rufous allele. These findings indicate that MC1R mutations not only alter the expression of melanogenic-related genes but also the association between coloration and the expression of melanocortin genes upstream of MC1R. This suggests that MC1R mutations can modulate the regulation of coloration by the pleiotropic melanocortin genes, potentially decoupling the often-observed associations between coloration and other phenotypes. PMID- 27664796 TI - Fully porous 3D printed titanium femoral stem to reduce stress-shielding following total hip arthroplasty. AB - Current hip replacement femoral implants are made of fully solid materials which all have stiffness considerably higher than that of bone. This mechanical mismatch can cause significant bone resorption secondary to stress shielding, which can lead to serious complications such as peri-prosthetic fracture during or after revision surgery. In this work, a high strength fully porous material with tunable mechanical properties is introduced for use in hip replacement design. The implant macro geometry is based off of a short stem taper-wedge implant compatible with minimally invasive hip replacement surgery. The implant micro-architecture is fine-tuned to locally mimic bone tissue properties which results in minimum bone resorption secondary to stress shielding. We present a systematic approach for the design of a 3D printed fully porous hip implant that encompasses the whole activity spectrum of implant development, from concept generation, multiscale mechanics of porous materials, material architecture tailoring, to additive manufacturing, and performance assessment via in vitro experiments in composite femurs. We show that the fully porous implant with an optimized material micro-structure can reduce the amount of bone loss secondary to stress shielding by 75% compared to a fully solid implant. This result also agrees with those of the in vitro quasi-physiological experimental model and the corresponding finite element model for both the optimized fully porous and fully solid implant. These studies demonstrate the merit and the potential of tuning material architecture to achieve a substantial reduction of bone resorption secondary to stress shielding. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1774-1783, 2017. PMID- 27664795 TI - Development of pea protein-based bioplastics with antimicrobial properties. AB - BACKGROUND: In the present work, bioplastics from renewable polymers were studied in order to reduce the huge generation of plastic wastes, causing an environmental problem that continues owing to the increasing demand for plastic products. RESULTS: Bioplastics with much better antimicrobial properties, in particular against Gram-positive bacteria, were obtained with the addition of nisin to the initial protein/plasticizer mixture. However, the addition of nisin produces more rigid but less deformable bioplastics (higher Young's modulus but lower strain at break). CONCLUSION: The results obtained are useful to demonstrate the antimicrobial properties of pea protein-based bioplastics by adding nisin and make them suitable as potential candidates to replace conventional plastics in food packaging. (c) 2016 Society of Chemical Industry. PMID- 27664797 TI - First-Year Waitlist Hospitalization and Subsequent Waitlist and Transplant Outcome. AB - Frailty is associated with inferior survival and increased resource requirements among kidney transplant candidates, but assessments are time-intensive and costly and require direct patient interaction. Waitlist hospitalization may be a proxy for patient fitness and could help those at risk of poor outcomes. We examined United States Renal Data System data from 51 111 adult end-stage renal disease patients with continuous Medicare coverage who were waitlisted for transplant from January 2000 to December 2011. Heavily admitted patients had higher subsequent resource requirements, increased waitlist mortality and decreased likelihood of transplant (death after listing: 1-7 days: hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.20-1.28; 8-14 days: HR 1.49, 95% CI 1.42-1.56; >=15 days: HR 2.07, 95% CI 1.99-2.15; vs. 0 days). Graft and recipient survival was inferior, with higher admissions, although survival benefit was preserved. A model including waitlist admissions alone performed better (C statistic 0.76, 95% CI 0.74-0.80) in predicting postlisting mortality than estimated posttransplant survival (C statistic 0.69, 95% CI 0.67-0.73). Although those with a heavy burden of admissions may still benefit from kidney transplant, less utility is derived from allografts placed in this population. Current kidney allocation policy, which is based in part on longevity matching, could be significantly improved by consideration of hospitalization records of transplant candidates. PMID- 27664798 TI - Assessment of Right Ventricular Strain by Computed Tomography Versus Echocardiography in Acute Pulmonary Embolism. AB - BACKGROUND: Right ventricular strain (RVS) identifies patients at risk of hemodynamic deterioration from pulmonary embolism (PE). Our hypothesis was that chest computed tomography (CT) can provide information about RVS analogous to transthoracic echocardiography (TTE) and that RVS on CT is associated with adverse outcomes after PE. METHODS: Consecutive emergency department patients with acute PE were prospectively enrolled and clinical, biomarker, and imaging data were recorded. CTs were overread by two radiologists. We compared diagnoses of RVS on CT (defined as right ventricle:left ventricle ratio >= 0.9 or interventricular septal bowing) to echocardiography (defined as right ventricular hypokinesis, right ventricular dilatation, or interventricular septal bowing). We calculated the test characteristics (with 95% confidence interval) of CT and TTE for a composite outcome of severe clinical deterioration, thrombolysis/thrombectomy, or death within 5 days. RESULTS: A total of 298 patients were enrolled; 274 had CT and 118 had formal TTE. Of the 104 patients who had both CT and TTE, the mean (+/-SD) age was 58 (+/-17) years; 50 (48%) were female and 88 (85%) were Caucasian. Forty-two (40%) had RVS by TTE and 75 (72%) had RVS by CT. CT and TTE agreed on the presence or absence of RVS in 61 (59%) cases (kappa = 0.24). Using TTE as criterion standard, the test characteristics of CT for RVS were as follows: sensitivity = 88%, specificity = 39%, positive predictive value = 49%, and negative predictive value = 83%. Fourteen (13%) patients experienced severe clinical deterioration or required hospital-based intervention within 5 days. This occurred in 30% of patients with RVS on both TTE and CT, 20% of patients with RVS on TTE alone, 3% of patients with RVS on CT alone, and 4% of patients without RVS on either modality. CONCLUSIONS: In acute PE, CT is highly sensitive but only moderately specific for RVS compared to TTE. RVS on both CT and TTE predicts more events than either modality alone. TTE confers additional positive prognostic value compared to CT in predicting post-PE clinical deterioration. PMID- 27664800 TI - Incidental finding of a true human tail in an adult: a case report. AB - True human tails are rare vestigial structures that are typically removed in childhood. Here a case is presented in which an inconspicuous sacrococcygeal tail was incidentally discovered in late adulthood. A 56-year-old man with no significant past medical history presented to a dermatology clinic with a chief complaint of a hyperpigmented lesion on his central back. However, on full body skin exam, a separate flesh-colored 0.7 cm * 0.5 cm appendage was discovered in the midline sacrococcygeal region. This lesion had been present and unchanged since childhood. This particular lesion was removed via shave biopsy. Microscopic exam found it to be consistent with a diagnosis of a true human tail. There were no apparent involved spinal cord structures, and no further treatment was thought to be necessary. Human tails are congenital anomalies associated with occult spinal lesions in about 50% of cases. Therefore, it is in these patients' best interest to thoroughly evaluate for spinal cord involvement prior to biopsy. There is a relative lack of literature published on the topic, and a greater awareness of human tails would be helpful to ensure their inclusion in a differential diagnosis for persistent sacrococcygeal lesions in patients of any age. PMID- 27664799 TI - Hepatitis E virus seroprevalence among farmers, veterinarians and control subjects in Jilin province, Shandong province and Inner Mongolia Autonomous Region, China. AB - China is commonly considered to be a HEV-endemic region but limited epidemiological data for HEV among farmers and veterinarians are available. Thus, a case-control study was carried out to detect the seroprevalence and assess potential risk factors associated with the acquisition of HEV infection by farmers and veterinarians in China from July 2013 to May 2015. Three hundred veterinarians and 600 farmers recruited from Jilin province, Shandong province, and Inner Mongolia Autonomous Region and 600 control subjects matched by gender, age, and residence were detected for the presence of anti-HEV IgG and IgM antibodies using enzyme immunoassays. The seroprevalences of HEV infection in farmers, veterinarians, and control subjects were 34.8%, 26.7%, and 20.2%, respectively. Farmers (P < 0.001) and veterinarians (P = 0.027) have significantly higher seroprevalence than control subjects. The highest seroprevalence of HEV infection was detected in swine farmers (49.1%) and the lowest seroprevalence was found in cattle farmers (26.5%). In veterinarians, farm animal veterinarians have a higher seroprevalence than pet veterinarians, but the difference was not significant (P > 0.05). Residence area, contact with swine and exposure with soil were significantly associated with HEV infection in the study farmers; contact with swine and source of drinking water were significantly associated with HEV infection in the study veterinarians. These results implied the high prevalence of HEV and the considerable potential for the dissemination of HEV infection in farmers and veterinarians in China. J. Med. Virol. 89:872 877, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27664801 TI - Is the unbound concentration of atazanavir of interest in therapeutic drug monitoring? AB - To date, therapeutic drug monitoring (TDM) is carried out with antiretrovirals and is usually based on total concentrations (Ct ). However, for some patients, TDM does not reflect efficacy or the avoidance of toxicity as is the case for atazanavir (ATV), a HIV protease inhibitor. As the unbound concentration (Cu ) is the pharmacological active form, the aim of the study was to evaluate the value of Cu and the unbound fraction (fu , fu = Cu /Ct ) for the TDM of ATV. The variability of Cu and the corresponding fu of ATV was explored in 43 patients treated with ATV for an average of 13.5 months. Cu was determined by coupling ultrafiltration and liquid chromatography. As ATV is highly bound to alpha-1 acid glycoprotein (AAG), the correlation between fu and AAG was also evaluated. The viral load was monitored to evaluate the patients' virologic response, while total plasma bilirubin and unconjugated plasma bilirubin were used as biomarkers of ATV toxicity. Median trough Cu and Ct were 37.9 MUg/L (Interquartile range (IQR) 20.6-94.9 MUg/L) and 628.6 MUg/L (IQR 362.7-1078.1 MUg/L), respectively. fu , Cu and Ct showed high variability, but the fu variability was not correlated with the AAG level. The unbound concentration and fraction were unrelated to the virologic response (P = 0.21 and P = 0.65 for Cu and fu , respectively) nor to the unconjugated bilirubin (Pearson correlation coefficient (rho), rho = 0.22; P = 0.17 for Cu ). Neither total nor unbound concentrations of ATV fully explained hyperbilirubinaemia or virologic failure. From this study, we conclude that unbound ATV did not appear to be more relevant than Ct . PMID- 27664802 TI - Influence of Late Vascular Inflammation on Long-Term Outcomes Among Patients Undergoing Implantation of Drug Eluting Stents: Role of C-Reactive Protein. AB - BACKGROUND: Elevation of C-reactive protein (CRP) as a marker of vascular inflammation at a late phase of drug-eluting stent (DES) implantation may predict subsequent major adverse cardiac events (MACE). METHODS AND RESULTS: In 1234 consecutive patients undergoing DES implantation, CRP was measured both before (baseline) and 8 to 12 months after (late phase) stenting, and the relationship between elevation of CRP (>2.0 mg/L) and subsequent MACE (all cause death, nonfatal myocardial infarction, target lesion revascularization, and other additional revascularization) was assessed. As results, CRP was elevated in 38.0% of patients at baseline and in 23.6% during late phase (P<0.0001), and hazard ratio (HR) for MACE was 1.52 (95% confidence interval [95% CI] 1.21-1.93, P=0.0004) at baseline versus 4.00 (95% CI 3.16-5.05, P<0.0001) in late phase. By multivariable analysis, late-phase CRP elevation (HR 3.60, 95% CI: 2.78-4.68, P<0.0001), chronic kidney disease (CKD) (HR 1.41, 95% CI: 1.10-1.84, P=0.01), and number of diseased segments (HR 1.19, 95% CI: 1.08-1.30, P=0.0002) were positive predictors of MACE, whereas statin use (HR 0.66, 95% CI 0.50-0.87, P=0.003) was a negative predictor. Propensity score-matched analysis also confirmed the effect of late-phase CRP on MACE (HR 3.39, 95% CI 2.52-4.56, P<0.0001). In prediction of the late-phase CRP elevation, CKD (odds ratio [OR] 1.71, 95% CI 1.24-2.36, P=0.001) and baseline CRP elevation (OR 3.48, 95% CI 2.55-4.74, P<0.0001) were positive predictors, whereas newer generation DES (OR 0.59, 95% CI 0.41-0.84, P=0.003) and statin therapy (OR 0.68, 95% CI 0.47-0.97, P=0.03) were negative predictors. CONCLUSIONS: Monitoring the late-phase CRP may be helpful to identify a high-risk subset for MACE among patients undergoing DES implantation. PMID- 27664803 TI - Left Internal Mammary Artery Versus Coronary Stents: Impact on Downstream Coronary Stenoses and Conduit Patency. AB - BACKGROUND: The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery (LIMA) versus percutaneous coronary intervention with bare metal stent (BMS) or drug eluting stent (DES). METHODS AND RESULTS: A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography (QCA; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan-Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow-up angiogram compared with BMS and DES (hazard ratio [HR] [95% CI], 0.34; [0.20-0.59]; P=0.0002; and HR [95% CI], 0.39; [0.20-0.79]; P=0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES (HR [95% CI], 0.18; [0.12-0.28]; P<0.001; and HR [95% CI], 0.27; [0.16-0.46]; P<0.001, respectively). BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES, but the difference did not reach statistical significance (HR [95% CI], 1.13; [0.57-2.36]; P=0.73; and HR [95% CI], 1.46; [0.88-2.50]; P=0.14, respectively). CONCLUSIONS: LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES. PMID- 27664804 TI - Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines. AB - BACKGROUND: Remote ischemic preconditioning (RIPC) is an attractive therapeutic procedure for protecting the heart against ischemia/reperfusion injury. Despite evidence of humoral mediators transported through the circulation playing a critical role, their actual identities so far remain unknown. We sought to identify plasmatic RIPC-induced metabolites that may play a role. METHODS AND RESULTS: Rat plasma samples from RIPC and control groups were analyzed using a targeted metabolomic approach aimed at measuring 188 metabolites. Principal component analysis and orthogonal partial least-squares discriminant analysis were used to identify the metabolites that discriminated between groups. Plasma samples from 50 patients subjected to RIPC were secondarily explored to confirm the results obtained in rats. Finally, a combination of the metabolites that were significantly increased in both rat and human plasma was injected prior to myocardial ischemia/reperfusion in rats. In the rat samples, 124 molecules were accurately quantified. Six metabolites (ornithine, glycine, kynurenine, spermine, carnosine, and serotonin) were the most significant variables for marked differentiation between the RIPC and control groups. In human plasma, analysis confirmed ornithine decrease and kynurenine and glycine increase following RIPC. Injection of the glycine and kynurenine alone or in combination replicated the protective effects of RIPC seen in rats. CONCLUSIONS: We have hereby reported significant variations in a cocktail of amino acids and biogenic amines after remote ischemic preconditioning in both rat and human plasma. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01390129. PMID- 27664805 TI - Trends in Transient Ischemic Attack Hospitalizations in the United States. AB - BACKGROUND: Transient ischemic attack (TIA) is a major predictor of subsequent stroke. No study has assessed nation-wide trends in hospitalization for TIA in the United States. METHODS AND RESULTS: Temporal trends in hospitalization for TIA (International Classification of Diseases, Ninth Revision code 435.0-435.9) from 2000 to 2010 were assessed among adults aged >=25 years using the Nationwide Inpatient Sample. Age-, sex-, and race/ethnic-specific TIA hospitalization rates were calculated using the weighted number of hospitalizations as the numerator and the US population as the denominator. Age-adjusted rates were standardized to the 2000 US Census population. From 2000 to 2010, age-adjusted TIA hospitalization rates decreased from 118 to 83 per 100 000 (overall rate reduction, -29.7%). Age-specific TIA hospitalization rates increased for individuals aged 24 to 44 years (10-11 per 100 000), but decreased for individuals aged 45 to 64 (74 to 65 per 100 000), 65 to 84 (398 to 245 per 100 000), and >=85 years (900 to 619 per 100 000). Blacks had the highest age adjusted yearly hospitalization rates, followed by Hispanics and whites (124, 82, and 67 per 100 000 in 2010). Rates slightly increased for blacks, but decreased for Hispanics and whites. Compared to women, age-adjusted TIA hospitalization rates were lower and declined more steeply in men (132 to 89 per 100 000 versus 134 to 97 per 100 000). CONCLUSIONS: Although overall TIA hospitalizations have decreased in the United States, the reduction has been more pronounced among older individuals, men, whites, and Hispanics. These findings highlight the need to target risk-factor control among women, blacks, and individuals aged <45 years. PMID- 27664806 TI - BubR1 Insufficiency Results in Decreased Macrophage Proliferation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice. AB - BACKGROUND: Budding uninhibited by benzimidazole-related 1 (BubR1), a cell cycle related protein, is an essential component of the spindle checkpoint that regulates cell division. BubR1 insufficiency causes early aging-associated vascular phenotypes. We generated low-BubR1-expressing mutant (BubR1L/L) and apolipoprotein E-deficient (ApoE-/-) mice (BubR1L/L-ApoE-/- mice) to investigate the effects of BubR1 on atherosclerosis. METHODS AND RESULTS: Eight-week-old male BubR1L/L-ApoE-/- mice and age-matched ApoE-/- mice were used in this study. Atherosclerotic lesion development after being fed a high-cholesterol diet for 12 weeks was inhibited in BubR1L/L-ApoE-/- mice compared with ApoE-/- mice, and was accompanied by decreased accumulation of macrophages. To address the relative contribution of BubR1 on bone marrow-derived cells compared with non-bone marrow derived cells, we performed bone marrow transplantation in ApoE-/- and BubR1L/L ApoE-/- mice. Decreased BubR1 in bone marrow cells and non-bone marrow-derived cells decreased the atherosclerotic burden. In vitro assays indicated that decreased BubR1 expression impaired proliferation, but not migration, of bone marrow-derived macrophages. CONCLUSIONS: BubR1 may represent a promising new target for regulating atherosclerosis. PMID- 27664807 TI - Endothelial Function and Arterial Stiffness Relate to Functional Outcomes in Adolescent and Young Adult Fontan Survivors. AB - BACKGROUND: Fontan survivors demonstrate diminished vascular function and functional outcomes, but the relationships between these measures have not been established. METHODS AND RESULTS: We performed a cross-sectional study of 60 Fontan survivors (52% male) with a mean age of 13.9+/-4.1 years and mean Fontan duration of 9.9+/-4.2 years. Multimodality assessment of endothelial function (reactive hyperemia index and flow-mediated dilation) and arterial stiffness (augmentation index and baseline pulse amplitude) was performed with peripheral arterial tonometry and brachial flow-mediated dilation. Aerobic capacity was determined using cardiopulmonary exercise testing; mean peak and percentage of predicted oxygen consumption (VO2) were 27.8+/-7.6 mL/kg per minute and 71.0+/ 21.2%, respectively. Quality of life and physical activity were assessed using the Pediatric Quality of Life Inventory (PedsQL) and the Physical Activity Questionnaire. Vascular measures served as predictor variables, whereas functional measures served as outcome variables. In all cases, worse vascular measures were associated with worse functional measures. Flow-mediated dilation derived reactive hyperemia index (P<0.05) was positively associated with VO2 at anaerobic threshold. Peripheral arterial tonometry-derived baseline pulse amplitude (P<0.05) was negatively associated with the ratio of minute ventilation to carbon dioxide at anaerobic threshold. Flow-mediated dilation-derived reactive hyperemia index and peripheral arterial tonometry-derived augmentation index (P<0.05) were positively and negatively associated, respectively, with peak VO2. Maximum flow-mediated dilation (P<0.05) was positively associated with Physical Activity Questionnaire score. Peripheral arterial tonometry-derived augmentation index and baseline pulse amplitude (P<0.05) were negatively associated with parent-reported PedsQL total and physical heath summary scores. CONCLUSIONS: Increased arterial stiffness and decreased endothelial function are associated with lower aerobic capacity, physical activity, and quality of life in adolescent and young adult Fontan survivors. Understanding the cause-effect relationship between vascular function and functional outcomes is an important next step. PMID- 27664809 TI - Finding lost genes in GWAS via integrative-omics analysis reveals novel sub networks associated with preterm birth. AB - Maternal genome influences associate with up to 40% of spontaneous preterm births (PTB). Multiple genome wide association studies (GWAS) have been completed to identify genetic variants associated with PTB. Disappointingly, no highly significant SNPs have replicated in independent cohorts so far. We developed an approach combining protein-protein interaction (PPI) network data with tissue specific gene expression data to "find" SNPs of modest significance to identify candidate genes of functional importance that would otherwise be overlooked. This approach is based on the assumption that "high-ranking" SNPs falling short of genome wide significance may nevertheless indicate genes that have substantial biological value in understanding PTB. We mapped highly-ranked candidate SNPs from a meta-analysis of PTB-GWAS to coding genes and developed a PPI network enriched with PTB-SNP carrying genes. This network was scored with gene expression data from term and preterm myometrium to identify subnetworks of PTB SNP associated genes coordinately expressed with labour onset in myometrial tissue. Our analysis consistently identified significant sub-networks associated with the interacting transcription factors MEF2C and TWIST1, genes not previously associated with PTB, both of which regulate processes clearly relevant to birth timing. Other genes in the significant sub-networks were also associated with inflammatory pathways, as well as muscle function and ion channels. Gene expression level dysregulation was confirmed for eight of these networks by qRT PCR in an independent set of term and pre-term subjects. Our method identifies novel genes dysregulated in PTB and provides a generalized framework to identify GWAS SNPs that would otherwise be overlooked. PMID- 27664810 TI - Timing matters: Endogenous cortisol mediates benefits from early-day psychotherapy. AB - OBJECTIVE: No simple way to augment fear extinction has been established. Cortisol has shown to enhance memory extinction and preliminary evidence suggest that extinction learning maybe more successful in the morning when cortisol is high. The aim was to determine whether exposure sessions conducted earlier in the day are associated with superior therapeutic gains in extinction-based psychotherapy. We also examined the role of cortisol levels as a mediator between time of day and therapeutic gains. METHOD: Participants were 24 individuals meeting DSM-IV criteria for panic disorder with agoraphobia. Participants received 3 weekly in-vivo exposure sessions, yielding 72 total sessions for analysis of time of day effects. Session start times were evenly distributed across the day. The outcome measures were reductions in panic symptom severity (avoidance behaviors, threat misappraisal, perceived control, and panic disorder symptom severity). RESULTS: Sessions starting earlier in the day were associated with superior therapeutic gains by the next therapy session. Earlier sessions were also associated with higher pre-exposure cortisol levels, which in turn were related to greater clinical improvement by the next session. Cortisol thus was found to mediate the effect of time of day on subsequent outcome, providing a link between earlier exposure sessions and greater clinical improvement. CONCLUSION: The data suggest that early-day extinction-based therapy sessions yield better outcomes than later-day sessions, partly due to the enhancing effect of higher cortisol levels. PMID- 27664811 TI - De novo assembly and characterization of the ovarian transcriptome reveal mechanisms of the final maturation stage in Chinese scallop Chlamys farreri. AB - The objective of the present study was to characterize the pattern of gene expression at the last stage of ovarian maturation in Chlamys farreri. Dynamic transcriptomic analysis of ovaries was performed at four time points prior to ovulation, using the Illumina HiSeq 2500 platform. A total of 174,928 unigenes were obtained, among which 42,534 were annotated according to bioinformatics databases, such as NT, NR, Swiss-Prot, KOG, GO, and KEGG. Results from the transcriptome analysis revealed a time-dependent pattern of global transcriptional responses. When compared to the 0 d library, 99, 152, and 3248 differently expressed genes (DEGs) were obtained in the 3, 10, and 21 d libraries, respectively. Those three libraries shared only 10 DEGs, the majority of which were time-specific. Pairwise comparisons of each profile demonstrated that DEGs were related to hormone metabolism and receptors, cell division, gametogenesis, and vitellogenesis pathways. Notably, when adjacent sampling time point groups were compared, the only DEG throughout the experimental period was related to the G protein-coupled receptor signaling pathway. The present study provides the first dynamic transcriptomic analysis of C. farreri for evaluation of the molecular basis of gonadal maturation. PMID- 27664812 TI - Mental health and psychosocial interventions for children and adolescents in street situations in low- and middle-income countries: A systematic review. AB - This article reviews the available quantitative literature on mental health and psychosocial interventions among children and adolescents in street situations (CASS) in low- and middle-income countries (LAMIC). PRISMA standards for systematic reviews were used to search five databases as well as grey literature. There were four inclusion criteria; studies had to involve a description of an external (i.e. outside of the home) mental health or psychosocial intervention/treatment, must be focused in LAMIC, must be focused on CASS, and must empirically evaluate the effectiveness of the intervention described. A quality assessment tool was used to assess the risk of bias in included articles. Five studies were included. A multidisciplinary care approach was significant in reducing psychological distress, substance use and improving sleeping arrangements (p<0.001, n=400). Residency step programmes were on average 52% successful in reintegrating children back into communities (n=863). Resilience training significantly increased psychological well-being components (p<0.001, n=60). Emotional regulation training had a beneficial improvement in emotional regulation. FORNET (Forensic Offender Rehabilitation Narrative Exposure Therapy) (n=32) reduced the number of self-reported offenses committed [t(19.26)=1.81, p=0.043]. There are not enough credible studies available to develop a firm conclusion on the effectiveness of mental health and psychosocial interventions delivered to CASS in LAMIC. The limited amount of studies, inconsistent outcome measures, interventions and imperfect study designs maintain that this is an area in need of greater attention and research focus. PMID- 27664813 TI - Mechanical characterization of sequentially layered photo-clickable thiol-ene hydrogels. AB - Multi-layer hydrogels are promising for tissue engineering due to the ability to control the local properties within each layer. However, the interface that forms between each layer has the potential to affect the performance of the hydrogel. The goals of this study were to characterize how the interface forms via its thickness and mechanical properties, identify its impact on the overall hydrogel properties, and provide new insights into how to control the interface. A photo clickable poly(ethylene glycol) hydrogel was used to form bilayer hydrogels that were sequentially polymerized in a step-and-repeat process. Different processing conditions were studied: the time (0-20min) before initiating polymerization of the second layer (soak time, ts) and the hydrogel crosslink density (the same, less crosslinked, or more crosslinked) of the first layer as compared to the second layer. Interface thickness was characterized by confocal microscopy, monomer transport by Fickian diffusion, single and bilayer hydrogel mechanics by bulk moduli measurements, and interface moduli measurements using AFM, nanoindentation, and strain mapping. The interface thickness ranged from ~70 to 600MUm (1-10% of total height) depending on processing conditions, but did not affect the bulk hydrogel modulus. Analysis of monomer transport revealed that convection, due to changes in hydrogel swelling, and diffusion contribute to interface thickness. Nanomechanical analysis of bilayer hydrogels formed from soft (75kPa) and stiff (250kPa) layers showed a gradient in elastic modulus across the interface, which corresponded to strain maps. In summary, this work identifies that diffusive and convective transport of monomers across the interface controls its thickness and that a mechanically robust interface forms, which does not affect the hydrogel modulus. By controlling the processing conditions, the thickness of the interface can be tuned without affecting the mechanical properties of the bulk hydrogel. PMID- 27664815 TI - Invited essay: Cognitive influences on the psychological immune system. AB - The construct of the psychological immune system is described and analysed. The direct and indirect cognitive influences on the system are discussed, and the implications of adding a cognitive construal to the influential model of a behavioural immune system are considered. The psychological immune system has two main properties: defensive and healing. It encompasses a good amount of health related phenomena that is outside the scope of the behavioural model or the biological immune system. Evidence pertaining to the psychological immune system includes meta-analyses of the associations between psychological variables such as positive affect/wellbeing and diseases and mortality, and associations between wellbeing and positive health. The results of long-term prospective studies are consistent with the conclusions drawn from the meta-analyses. Laboratory investigations of the effects of psychological variables on the biological immune system show that negative affect can slow wound-healing, and positive affect can enhance resistance to infections, for example in experiments involving the introduction of the rhinovirus and the influenza A virus. A number of problems concerning the assessment of the functioning of the psychological immune system are considered, and the need to develop techniques for determining when the system is active or not, is emphasized. This problem is particularly challenging when trying to assess the effects of the psychological immune system during a prolonged psychological intervention, such as a course of resilience training. PMID- 27664816 TI - "What I believe is true": Belief-confirming reasoning bias in social anxiety disorder. AB - BACKGROUND AND OBJECTIVES: Research shows that people tend to consider believable conclusions as valid and unbelievable conclusions as invalid (belief bias). When applied to anxiogenic beliefs, this belief bias could well hinder the correction of dysfunctional convictions. Previous work has shown that high socially anxious students indeed display such fear-confirming, belief biased, reasoning. A critical next question is whether these findings translate to a clinical population of people with social anxiety disorder (SAD). We test whether (i) patients with SAD show belief bias with regard to SAD-relevant themes, (ii) this belief bias is specific for SAD patients or can also be found in panic disorder (PD) patients, (iii) differential belief bias effects in SAD are restricted to social anxiety concerns or are also evident in the context of reasoning with neutral themes. METHOD: 45 SAD patients, 24 PD patients, and 45 non-symptomatic controls (NSCs) completed a syllogistic belief bias task with SAD-relevant and neutral content. RESULTS: SAD patients displayed belief bias for social anxiety related materials, while the PD group and the NSC group did not. Yet, the difference between SAD and PD was not significant. All groups showed similar belief bias effects for neutral content. LIMITATIONS: Content of the belief bias task was not tailored to idiosyncratic beliefs. The study lacked power to detect medium or small differences. CONCLUSIONS: SAD patients showed concern-congruent belief biased interference effects when judging the logical validity of social anxiety relevant syllogisms. Such concern-relevant belief bias may contribute to the persistence of anxiogenic beliefs. PMID- 27664817 TI - Stove checking behaviour in people with OCD vs. anxious controls. AB - BACKGROUND AND OBJECTIVES: A growing body of research suggests that the repetition of an action degrades memory for that action, as well as confidence that is has been done correctly. This has important implications for understanding the compulsive repetition of actions characteristic of obsessive compulsive disorder (OCD). At this time, though, much of the research has been conducted on analogue or nonclinical OCD samples in comparison to healthy controls and often using virtual, as opposed to actual, threat stimuli. Furthermore, although it has been argued that people with OCD are overly attentive to threat stimuli, the research on actual attention to threat is scant. METHODS: People with a principal diagnosis of OCD (n = 30) and people with a clinically significant diagnosis of an anxiety disorder, but no OCD (n = 18) completed measures of memory confidence and responsibility and then underwent a stove-checking task in a functioning kitchen while wearing a portable eye tracking device. Pre- and post-task ratings of harm and responsibility were taken, along with post-task ratings of memory and certainty. RESULTS: People with OCD did not exhibit poorer memory confidence than the anxious control (AC) group, but did report greater trait and state responsibility for harm. The OCD group checked longer than did the AC group and check duration predicted post-task ratings of harm, but to the same extent in both groups. People with OCD attended to threat items less than did the AC group. Greater visual attention to the stove during the checking period was associated with greater post-task ratings of responsibility and harm and with less certainty in and memory for the check - but only for the AC group. LIMITATIONS: The sample size was modest, women were over represented and problems with the eye tracking device reduced the amount of reliable data available for analysis. CONCLUSIONS: Compulsions are complex actions that are mediated by many trait, state and contextual factors. People with OCD may be able to circumvent self-perpetuating checking processes under certain circumstances. Future research should explore the factors that determine whether or not self-perpetuating mechanisms are activated. PMID- 27664818 TI - Playing the computer game Tetris prior to viewing traumatic film material and subsequent intrusive memories: Examining proactive interference. AB - BACKGROUND AND OBJECTIVES: Visuospatial working memory (WM) tasks performed concurrently or after an experimental trauma (traumatic film viewing) have been shown to reduce subsequent intrusive memories (concurrent or retroactive interference, respectively). This effect is thought to arise because, during the time window of memory consolidation, the film memory is labile and vulnerable to interference by the WM task. However, it is not known whether tasks before an experimental trauma (i.e. proactive interference) would also be effective. Therefore, we tested if a visuospatial WM task given before a traumatic film reduced intrusions. Findings are relevant to the development of preventative strategies to reduce intrusive memories of trauma for groups who are routinely exposed to trauma (e.g. emergency services personnel) and for whom tasks prior to trauma exposure might be beneficial. METHODS: Participants were randomly assigned to 1 of 2 conditions. In the Tetris condition (n = 28), participants engaged in the computer game for 11 min immediately before viewing a 12-min traumatic film, whereas those in the Control condition (n = 28) had no task during this period. Intrusive memory frequency was assessed using an intrusion diary over 1-week and an Intrusion Provocation Task at 1-week follow-up. Recognition memory for the film was also assessed at 1-week. RESULTS: Compared to the Control condition, participants in the Tetris condition did not report statistically significant difference in intrusive memories of the trauma film on either measure. There was also no statistically significant difference in recognition memory scores between conditions. LIMITATIONS: The study used an experimental trauma paradigm and findings may not be generalizable to a clinical population. CONCLUSIONS: Compared to control, playing Tetris before viewing a trauma film did not lead to a statistically significant reduction in the frequency of later intrusive memories of the film. It is unlikely that proactive interference, at least with this task, effectively influences intrusive memory development. WM tasks administered during or after trauma stimuli, rather than proactively, may be a better focus for intrusive memory amelioration. PMID- 27664819 TI - Comparisons of eye movements and matched changing visual input. AB - BACKGROUND AND OBJECTIVES: During EMDR trauma therapy, performing EM taxes WM, and simultaneously recalled memories become less vivid. It has been proposed that this WM occupation results from CVI which occurs during EM. This study sought to compare the effects of EM on memory to a task presenting identical visual stimulus to stationary eyes.. METHOD: In Study 1, participants recorded RT while performing two tasks: EM, and a task with visually identical images displayed on screen. In Study 2, these same tasks were performed while simultaneously recalling negative emotional memories. RESULTS: Study 1 found RT was slowest in the EM condition, while RT in the CVI condition was still slower than in the control condition. Study 2 found decreases in memory vividness and emotionality after EM, while after CVI there was a small decrease in negativity which was not greater than in the control.. LIMITATIONS: Neither study included EM with no visual input; conclusions cannot be made about the effect of motor movement on WM taxation or recall. As neither study was conducted with trauma patients, it is unknown if the observed effects would be comparable in the population for which EMDR is intended. CONCLUSIONS: Performing EM taxes more WM resources and has greater impact on both memory vividness and emotionality than matched CVI. This demonstrates that the effects observed in EMDR treatment are the result of more than occupying WM systems with visual stimuli alone.. PMID- 27664820 TI - Usefulness of quality indicators for antibiotic use: case study for the Netherlands. AB - Quality problem: Inappropriate antibiotic use drives development of antimicrobial resistance. Worldwide, guideline adherence for antibiotic treatment of infectious disease is far from optimal. Insight in prescribing quality is pivotal for healthcare professionals and policy makers to intervene appropriately. Initial assessments: European countries uniformly monitor antibiotic use, which is reported yearly by the European Centre for Disease Prevention and Control. Unfortunately, this has not had enough impact to decrease prescribing and resistance levels. Choice of solution: Quality indicators (QIs) could provide better insight in prescribing quality and enable benchmarking to other countries; this could trigger action to improve antimicrobial prescribing. European Surveillance of Antimicrobial Consumption (ESAC) proposed 12 antibiotic QIs. Implementation: Trends in use of antibiotic subgroups and the 12 ESAC QI values were determined for Dutch primary care (2004-2013); outcomes were compared to other European countries. Dutch antibiotic use is low within the European context. Nitrofurantoin use is higher than the European average, use of small spectrum antibiotics lowers. Use of macrolides, quinolones and amoxicillin/clavulanate declined, which was not supported by the broad/narrow QI results. Evaluation: QIs expressing antibiotic subgroup use in Defined Daily Doses/1000 inhabitants/day, particularly small-spectrum and non-first choices, provide proper insight in prescribing quality and are useful for benchmarking purposes. QIs measuring percentages were not considered useful. The broad/narrow ratio could be more informative when adjusted to national guidelines, or when more antibiotic subgroups are included based on better European consensus. Lessons learnt: Benchmarking the above mentioned Dutch QI values to other countries provides direction for three specific strategies to further improve Dutch antibiotic prescribing practice. PMID- 27664822 TI - The application of the Global Trigger Tool: a systematic review. AB - Purpose: This study describes the use of, and modifications and additions made to, the Global Trigger Tool (GTT) since its first release in 2003, and summarizes its findings with respect to counting and characterizing adverse events (AEs). Data sources: Peer-reviewed literature up to 31st December 2014. Study selection: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data extraction: Two authors extracted and compiled the demographics, methodologies and results of the selected studies. Results of data synthesis: Of the 48 studies meeting the eligibility criteria, 44 collected data from inpatient medical records and four from general practice records. Studies were undertaken in 16 countries. Over half did not follow the standard GTT protocol regarding the number of reviewers used. 'Acts of omission' were included in one quarter of studies. Incident reporting detected between 2% and 8% of AEs that were detected with the GTT. Rates of AEs varied in general inpatient studies between 7% and 40%. Infections, problems with surgical procedures and medication were the most common incident types. Conclusion: The GTT is a flexible tool used in a range of settings with varied applications. Substantial differences in AE rates were evident across studies, most likely associated with methodological differences and disparate reviewer interpretations. AE rates should not be compared between institutions or studies. Recommendations include adding 'omission' AEs, using preventability scores for priority setting, and re-framing the GTT's purpose to understand and characterize AEs rather than just counting them. PMID- 27664821 TI - The effect of a short educational intervention on the use of urinary catheters: a prospective cohort study. AB - Objective: To assess the effectiveness of implementation of evidence-based recommendations to reduce catheter-associated urinary tract infections (CAUTIs). Design: Prospective cohort study, conducted in 2010-12, with a before and after design. Setting: A major referral university hospital. Participants: Data were collected before (n = 244) and 1 year after (n = 255) the intervention for patients who received urinary catheters. Intervention: The intervention comprised two elements: (i) aligning doctors' and nurses' knowledge of indications for the use of catheters and (ii) an educational effort consisting of three 30- to 45 minute sessions on evidence-based practice regarding catheter usage for nursing personnel on 17 medical and surgical wards. Main Outcome Measures: The main outcome measures were the proportion of (i) admitted patients receiving urinary catheters during hospitalization, (ii) catheters inserted without indication, (iii) inpatient days with catheter and (iv) the incidence of CAUTIs per 1000 catheter days. Secondary outcome measures were the proportion of (i) catheter days without appropriate indication and (ii) patients discharged with a catheter. Results: There was a reduction in the proportion of inpatient days with a catheter, from 44% to 41% (P = 0.006). There was also a reduction in the proportion of catheter days without appropriate indication (P < 0.001) and patients discharged with a catheter (P = 0.029). The majority of catheters were inserted outside the study wards. Conclusions: A short educational intervention was feasible and resulted in significant practice improvements in catheter usage but no reduction of CAUTIs. Other measures than CAUTI may be more sensitive to detecting important practice changes. PMID- 27664824 TI - Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control. AB - Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo opercular network may be associated with diminished impulse control. PMID- 27664823 TI - The role of masculinity in men's help-seeking for depression: A systematic review. AB - AIM: Conformity to traditional masculine gender norms may deter men's help seeking and/or impact the services men engage. Despite proliferating research, current evidence has not been evaluated systematically. This review summarises findings related to the role of masculinity on men's help-seeking for depression. METHOD: Six electronic databases were searched using terms related to masculinity, depression and help-seeking. Titles and abstracts were reviewed and data systematically extracted and examined for methodological quality. RESULTS: Of 1927 citations identified, 37 met inclusion criteria. Seventeen (46%) studies reported qualitative research; eighteen (49%) employed quantitative methods, and two (5%) mixed methods. Findings suggest conformity to traditional masculine norms has a threefold effect on men experiencing depression, impacting: i) their symptoms and expression of symptoms; ii) their attitudes to, intention, and, actual help-seeking behaviour; and, iii) their symptom management. CONCLUSION: Results demonstrate the problematic impact of conformity to traditional masculine norms on the way men experience and seek help for depression. Tailoring and targeting clinical interventions may increase men's service uptake and the efficacy of treatments. Future research examining factors associated with men's access to, and engagement with depression care will be critical to increasing help-seeking, treatment uptake, and effectual self-management among men experiencing depression. PMID- 27664825 TI - Selective interhemispheric circuits account for a cardinal bias in spontaneous activity within early visual areas. AB - Ongoing brain activity exhibits patterns resembling neural ensembles co-activated by stimulation or task performance. Such patterns have been attributed to the brain's functional architecture, e.g. selective long-range connections. Here, we directly investigate the contribution of selective connections between hemispheres to spontaneous and evoked maps in cat area 18 close to the 17/18 border. We recorded voltage-sensitive dye imaging maps and spiking activity while manipulating interhemispheric input by reversibly deactivating corresponding contralateral areas. During deactivation, spontaneous maps continued to be generated with similar frequency and quality as in the intact network but a baseline cardinal bias disappeared. Consistently, neurons preferring either horizontal (HN) or vertical (VN), as opposed to oblique contours, decreased their resting state activity. HN decreased their rates also when stimulated visually. We conclude that structured spontaneous maps are primarily generated by thalamo- and/or intracortical connectivity. However, selective long-range connections through the corpus callosum - in perpetuation of the long-range intracortical network - contribute to a cardinal bias, possibly, because they are stronger or more frequent between neurons preferring horizontal and/or cardinal contours. As those contours are easier perceived and appear more frequently in natural environment, long-range connections might provide visual cortex with a grid for probabilistic grouping operations in a larger visual scene. PMID- 27664826 TI - Neural bases of the adaptive mechanisms associated with reciprocal partner choice. AB - In our society, partner choice is often reciprocal and, therefore, compromising one's choice may be adaptive depending on one's own market price. To reveal the neural mechanisms underlying this adaptive process, functional magnetic resonance imaging (fMRI) was performed on 27 male subjects during virtual partner choice tasks involving a dance-partner choice or a part-time job choice. Following the evaluation of a rival, the subjects chose a partner either in the face of competition with a rival (reciprocal choice condition) or during no competition (nonreciprocal condition). Irrespective of the type of partner choice situation, the posterior cingulate cortex (PCC) and right temporoparietal junction (TPJ) were specifically activated during reciprocal partner choice. The PCC was also activated during the evaluation of a rival relative to the self, which indicates the involvement of this region in the processing of one's own market price. Activation in the right TPJ was related to the individual tendency to avoid choosing a higher-value candidate when the rival-value was high in the reciprocal choice condition, which indicates that this region plays a role in market adaptive strategy. Taken together with extant anatomical knowledge, the two component neurobiological structure underlying the adaptive mechanism of partner choice identified in this study seems to represent the hierarchical evolution of the human socio-cognitive system. PMID- 27664827 TI - Predicting symptom severity in autism spectrum disorder based on cortical thickness measures in agglomerative data. AB - Machine learning approaches have been widely used for the identification of neuropathology from neuroimaging data. However, these approaches require large samples and suffer from the challenges associated with multi-site, multi-protocol data. We propose a novel approach to address these challenges, and demonstrate its usefulness with the Autism Brain Imaging Data Exchange (ABIDE) database. We predict symptom severity based on cortical thickness measurements from 156 individuals with autism spectrum disorder (ASD) from four different sites. The proposed approach consists of two main stages: a domain adaptation stage using partial least squares regression to maximize the consistency of imaging data across sites; and a learning stage combining support vector regression for regional prediction of severity with elastic-net penalized linear regression for integrating regional predictions into a whole-brain severity prediction. The proposed method performed markedly better than simpler alternatives, better with multi-site than single-site data, and resulted in a considerably higher cross validated correlation score than has previously been reported in the literature for multi-site data. This demonstration of the utility of the proposed approach for detecting structural brain abnormalities in ASD from the multi-site, multi protocol ABIDE dataset indicates the potential of designing machine learning methods to meet the challenges of agglomerative data. PMID- 27664828 TI - Neurovascular unit remodelling in the subacute stage of stroke recovery. AB - Brain plasticity following focal cerebral ischaemia has been observed in both stroke survivors and in preclinical models of stroke. Endogenous neurovascular adaptation is at present incompletely understood yet its potentiation may improve long-term functional outcome. We employed longitudinal MRI, intracranial array electrophysiology, Montoya Staircase testing, and immunofluorescence to examine function of brain vessels, neurons, and glia in addition to forelimb skilled reaching during the subacute stage of ischemic injury progression. Focal ischemic stroke (~100mm3 or ~20% of the total brain volume) was induced in adult Sprague Dawley rats via direct injection of endothelin-1 (ET-1) into the right sensori motor cortex, producing sustained impairment in left forelimb reaching ability. Resting perfusion and vascular reactivity to hypercapnia in the peri-lesional cortex were elevated by approximately 60% and 80% respectively seven days following stroke. At the same time, the normal topological pattern of local field potential (LFP) responses to peripheral somatosensory stimulation was abolished and the average power of spontaneous LFP activity attenuated by approximately 50% relative to the contra-lesional cortex, suggesting initial response attenuation within the peri-infarct zone. By 21 days after stroke, perilesional blood flow resolved, but peri-lesional vascular reactivity remained elevated. Concomitantly, the LFP response amplitudes increased with distance from the site of ET-1 injection, suggesting functional remodelling from the core of the lesion to its periphery. This notion was further buttressed by the lateralization of spontaneous neuronal activity: by day 21, the average ipsi-lesional power of spontaneous LFP activity was almost twice that of the contra-lesional cortex. Over the observation period, the peri-lesional cortex exhibited increased vascular density, along with neuronal loss, astrocytic activation, and recruitment and activation of microglia and macrophages, with neuronal loss and inflammation extending beyond the peri-lesional cortex. These findings highlight the complex relationship between neurophysiological state and behaviour and provide evidence of highly dynamic functional changes in the peri-infarct zone weeks following the ischemic insult, suggesting an extended temporal window for therapeutic interventions. PMID- 27664829 TI - Activity/rest cycle and disturbances of structural backbone of cerebral networks in aging. AB - OBJECTIVE: Although aging is associated with alterations of both activity/rest cycle and brain structure, few studies have evaluated associations between these processes. The aim of this study was to examine relationship between activity/rest cycle quality and brain structural integrity in aging subjects by exploring both grey and white matter compartments. MATERIAL AND METHODS: Fifty eight elderly subjects (76+/-0.5 years; 41% female) without dementia, sleep disorders and medications were included in the analysis. Actigraphy was used to measure parameters of activity/rest cycle (24-h amplitude, 24-h fragmentation and 24-h stability) and sleep (total sleep time and sleep fragmentation) over a minimal period of 5 days. Whole brain linear regression analyses were performed on grey matter volumes maps using voxel based morphometry and on white matter integrity using tract based statistics analyses. RESULTS: A lower 24-h amplitude and a higher sleep fragmentation were independently associated with a reduction of white matter integrity in models including age and gender as covariates. The association between 24-h amplitude and white matter integrity decreased but remained significant in a model accounted for sleep fragmentation, indicating a specific effect of 24-h cycle disturbances. No association with grey matter volumes was observed. CONCLUSION: In elderly, not only sleep but also 24-h cycle disturbances were associated with altered structural connectivity. This alteration of structural backbone networks related to activity/rest cycle disturbances in aging might constitute a cerebral frailty factor for the development of cognitive impairment. PMID- 27664831 TI - Algal toxins and producers in the marine waters of Qatar, Arabian Gulf. AB - Harmful Algal Bloom species are ubiquitous and their blooms occur in the Arabian Gulf. In this study, two cruises were performed in 2012 and 2013 to collect phytoplankton samples from 4 sites in the Arabian Gulf. Toxin analyses of phytoplankton samples for 32 algal toxins from 5 different toxin groups were conducted on the samples using both enzyme linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results demonstrated, for the first time, the presence of paralytic shellfish toxins (PSTs), diarrhetic shellfish toxin (DST), amnesic shellfish toxin (AST), cyclic imines (CIs) and polyether-lactone toxins in freeze-dried phytoplankton samples. Four Vulcanodinium rugosum cultures were established from field samples and these proved to contain between 603 and 981 ng pinnatoxin (PnTx) H per mg dry weight in addition to being positive for portimine. These strains from Qatar clustered with strains from Japan and Florida based on large subunit rRNA and rRNA internal transcribed spacer gene sequences. PMID- 27664832 TI - Anxiolytic-like effect of a novel peptide isolated from the venom of the social wasp Synoeca surinama. AB - Pathological anxiety is among the most common psychiatric illnesses, but current treatment is highly limited. In this study, we investigated the potential anxiolytic-like effects of a peptide isolated from Synoeca surinama venom. Rats treated with this peptide spent more time exploring the open arms of elevated plus maze, which indicates an anxiolytic-like profile for this peptide. This study is the first to show the pharmacological use of S. surinama venom in the treatment of anxiety. PMID- 27664830 TI - g-Ratio weighted imaging of the human spinal cord in vivo. AB - The fiber g-ratio is defined as the ratio of the inner to the outer diameter of the myelin sheath. This ratio provides a measure of the myelin thickness that complements axon morphology (diameter and density) for assessment of demyelination in diseases such as multiple sclerosis. Previous work has shown that an aggregate g-ratio map can be computed using a formula that combines axon and myelin density measured with quantitative MRI. In this work, we computed g ratio weighted maps in the cervical spinal cord of nine healthy subjects. We utilized the 300mT/m gradients from the CONNECTOM scanner to estimate the fraction of restricted water (fr) with high accuracy, using the CHARMED model. Myelin density was estimated using the lipid and macromolecular tissue volume (MTV) method, derived from normalized proton density (PD) mapping. The variability across spinal level, laterality and subject were assessed using a three-way ANOVA. The average g-ratio value obtained in the white matter was 0.76+/-0.03, consistent with previous histology work. Coefficients of variation of fr and MTV were respectively 4.3% and 13.7%. fr and myelin density were significantly different across spinal tracts (p=3*10-7 and 0.004 respectively) and were positively correlated in the white matter (r=0.42), suggesting shared microstructural information. The aggregate g-ratio did not show significant differences across tracts (p=0.6). This study suggests that fr and myelin density can be measured in vivo with high precision and that they can be combined to produce a g-ratio-weighted map robust to free water pool contamination from cerebrospinal fluid or veins. Potential applications include the study of early demyelination in multiple sclerosis, and the quantitative assessment of remyelination drugs. PMID- 27664833 TI - Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats. AB - AIMS: In this study, the renoprotective functions of sinapic acid (SA), a polyphenol, on gentamicin-induced nephrotoxicity and the pathway that mediates this function were examined. MAIN METHODS: Kidney function markers (serum urea, uric acid, creatinine, LDH, and gamma-GGT) and histopathological examinations of the kidney were used to evaluate gentamicin-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-kappaB [p65], TNF-alpha, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed. KEY FINDINGS: SA (10 and 20mg/kg) pretreatment along with gentamicin restored kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels, resulting in significant decreases in oxidative and nitrosative stress. Gentamicin promoted the upregulation of renal cytokines (TNF-alpha and IL-6), nuclear NF-kappaB (p65) expression, NF-kappaB-DNA binding activity, and MPO activity were significantly down regulated upon SA pretreatment. Furthermore, SA pretreatment downregulated caspase 3 and Bax protein expressions and upregulated Bcl-2 protein expression. SA pretreatment also mitigated the magnitude of histological damage and reduced neutrophil infiltration in renal tubules. SIGNIFICANCE: These outcomes indicated that SA pretreatment mitigates renal impairment and structural injuries via the downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney. PMID- 27664834 TI - Changes in Relatives' Perspectives on Quality of Death, Quality of Care, Pain Relief, and Caregiving Burden Before and After a Region-Based Palliative Care Intervention. AB - CONTEXT: A region-based palliative care intervention (Outreach Palliative Care Trial of Integrated Regional Model Study) increased home death, access to specialist palliative care, quality of care, and quality of death and dying. OBJECTIVES: The objective of this study was to examine changes in palliative care outcomes in different care settings (hospitals, palliative care units, and home) and obtain insights into how to improve region-level palliative care. METHODS: The intervention program was implemented from April 2008 to March 2011. Two bereavement surveys were conducted before and after intervention involving 4228 family caregivers of deceased cancer patients. Family-perceived quality of care (range 1-6), quality of death and dying (1-7), pain relief (1-7), and caregiver burden (1-7) were measured. RESULTS: Response rates were 69% (preintervention) and 66% (postintervention), respectively. Family-perceived quality of care (adjusted mean 4.89, 95% CI 4.54-5.23) and quality of death and dying (4.96, 4.72 5.20) at home were the highest and sustained throughout the study. Palliative care units were at the intermediate level between home and hospitals. In hospitals, both quality of care and quality of death and dying were low at baseline but significantly improved after intervention (quality of care: 4.24, 4.13-4.34 to 4.43, 4.31-4.54, P = 0.002; quality of death and dying: 4.22, 4.09 4.36 to 4.36, 4.22-4.50, P = 0.012). Caregiver burden did not significantly increase after intervention, regardless of place of death. CONCLUSIONS: The dual strategies of transition of place of death to home and improving quality of care in hospitals should be recognized as important targets for improving region-level palliative care. PMID- 27664836 TI - Search for KPNA7 cargo proteins in human cells reveals MVP and ZNF414 as novel regulators of cancer cell growth. AB - Karyopherin alpha 7 (KPNA7) belongs to a family of nuclear import proteins that recognize and bind nuclear localization signals (NLSs) in proteins to be transported to the nucleus. Previously we found that KPNA7 is overexpressed in a subset of pancreatic cancer cell lines and acts as a critical regulator of growth in these cells. This characteristic of KPNA7 is likely to be mediated by its cargo proteins that are still mainly unknown. Here, we used protein affinity chromatography in Hs700T and MIA PaCa-2 pancreatic cancer cell lines and identified 377 putative KPNA7 cargo proteins, most of which were known or predicted to localize to the nucleus. The interaction was confirmed for two of the candidates, MVP and ZNF414, using co-immunoprecipitation, and their transport to the nucleus was hindered by siRNA based KPNA7 silencing. Most importantly, silencing of MVP and ZNF414 resulted in marked reduction in Hs700T cell growth. In conclusion, these data uncover two previously unknown human KPNA7 cargo proteins with distinct roles as novel regulators of pancreatic cancer cell growth, thus deepening our understanding on the contribution of nuclear transport in cancer pathogenesis. PMID- 27664835 TI - Polymorphisms in Cytokine Genes Are Associated With Higher Levels of Fatigue and Lower Levels of Energy in Women After Breast Cancer Surgery. AB - CONTEXT: Little is known about the phenotypic and molecular characteristics associated with changes over time in fatigue and lack of energy in patients with breast cancer. OBJECTIVES: The aim of this study was to identify subgroups (i.e., latent classes) of women with distinct fatigue and energy trajectories; evaluate for differences in phenotypic characteristics between the latent classes for fatigue and energy; and evaluate for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators and latent class membership. METHODS: Patients were enrolled before and followed for six months after breast cancer surgery. Latent class analyses were done to identify subgroups of patients with distinct fatigue and energy trajectories. Candidate gene analyses were done to identify cytokine genes associated with these two symptoms. RESULTS: For both fatigue and lack of energy, two distinct latent classes were identified. Phenotypic characteristics associated with the higher fatigue class were younger age, higher education, lower Karnofsky Performance Status score, higher comorbidity, higher number of lymph nodes removed, and receipt of chemotherapy (CTX). Polymorphisms in interleukin (IL) 1beta and IL10 were associated with membership in the higher fatigue class. Phenotypic characteristics associated with the lower energy class included: a lower Karnofsky Performance Status score and a higher comorbidity score. A polymorphism in IL1R1 was associated with membership in the lower energy class. CONCLUSION: Within each latent class, the severity of fatigue and decrements in energy were relatively stable over the first six months after breast cancer surgery. Distinct phenotypic characteristics and genetic polymorphisms were associated with membership in the higher fatigue and lower energy classes. PMID- 27664837 TI - Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication. AB - Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/local administration of histone deacetylase inhibitors. However, the role of other epigenetic mechanisms such as histone lysine methylation and demethylation in stroke-induced damage and subsequent recovery process is elusive. Here, we established an Internal Carotid Artery Occlusion (ICAO) model in CD1 mouse that resulted in mild to moderate level of ischemic damage to the striatum, as suggested by magnetic resonance imaging (MRI), TUNEL and histopathological staining along with an evaluation of neurological deficit score (NDS), grip strength and rotarod performance. The molecular investigations show dysregulation of a number of histone lysine methylases (KMTs) and few of histone lysine demethylases (KDMs) post-ICAO with significant global attenuation in the transcriptionally repressive epigenetic mark H3K9me2 in the striatum. Administration of Dimethyloxalylglycine (DMOG), an inhibitor of KDM4 or JMJD2 class of histone lysine demethylases, significantly ameliorated stroke-induced NDS by restoring perturbed H3K9me2 levels in the ischemia-affected striatum. Overall, these results highlight the novel role of epigenetic regulatory mechanisms controlling the epigenetic mark H3K9me2 in mediating the stroke induced striatal damage and subsequent repair following mild to moderate cerebral ischemia. PMID- 27664838 TI - Human cytomegalovirus infection and vascular disease risk: A meta-analysis. AB - BACKGROUND: Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease. Numbers studies were conducted to analyze the association between HCMV infection and risk of vascular disease, but no clear consensus had been reached. The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. METHODS: We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: (1) evaluating the association between HCMV infection and vascular disease; (2) case-control studies or nested case-control studies; (3) and supply the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. Ultimately, We included data from 68 studies, which altogether enrolled 12027 cases and 15386 controls from 24 countries. RESULTS: HCMV IgG was detected 7376 in 10611 cases, HCMV IgM was detected 153 in 1486 cases and HCMV DNA was detected 654 in 2139 cases. Overall, people exposed to HCMV infection had higher risk than those not exposed for vascular disease (OR 1.70 [95% CI 1.43 2.03] IgG-based HCMV tests, 2.88 [95% CI 1.87-4.43] IgM-based HCMV tests and 2.56 [95% CI 1.46-4.49 PCR-based HCMV tests]). HCMV infection was clearly identified as a risk factor for vascular disease in Asian group, Caucasian group and other group, especially Asian group(OR 1.86 [95% CI 1.33-2.60] IgG-based HCMV tests, 3.57 [95% CI 1.94-6.60] IgM-based HCMV tests and 4.09 [95% CI 3.10-5.40 PCR-based HCMV tests]). CONCLUSION: This meta-analysis suggested that HCMV infection is associated with an increased risk for vascular disease. PMID- 27664840 TI - Risk assessment in combustion toxicology: Should carbon dioxide be recognized as a modifier of toxicity or separate toxicological entity? AB - To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard ISO 13571. The current FED calculation related to asphyxiant gases is based on non-human primate data to estimate the 50% probability of humans to be incapacitated or not being able to execute any escape paradigm from fires. The objective of this paper was to compare two to calculate FEDs of the most common mixture of asphyxiant fire gases CO, HCN, and CO2. The first was based on the current ISO 13571 (draft) standard, the alternative second method applied the conceptual principles established for the derivation of Acute Emergency Response Planning Guideline values. The alternative approach applied one third of the non lethal threshold concentration (LC01) as the most suitable and robust Point of Departure (POD) to estimate the threshold characterizing 'impairment of escape' in the absence of post-exposure mortality. The hyperventilation correction factor for CO2 of ISO 13571 was replaced by a separate term that accounts for the inherent acute toxicity of CO2. This analysis supports the conclusion that the current ISO 13571 standard misjudges the impact of the acute toxicity elicited by concentrations of CO2 exceeding ~6%. While underestimating the hazards attributable to CO2, the hyperventilation adjustment factor suggested by this standard is biased to markedly overestimate the hazards assigned to CO and HCN in fire effluents. PMID- 27664839 TI - Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X. AB - The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6F47R) and E7 (E7GGG) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6F47RCP and E7GGGCP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6F47RCP and DNAE7GGGCP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6F47RCP and in particular E7GGGCP were administered alone. PMID- 27664841 TI - IL28B gene variants and glucose metabolism in Type 2 Diabetes. AB - Type 2 Diabetes (T2D) develops, when beta-cell insulin response fails to compensate for insulin resistance. Recent studies reported associations between the IL28B polymorphisms (rs12979860 and rs8099917) and T2D development in Hepatitis C virus (HCV) patients. To identify possible association with T2D independent from virus infection, we investigated both IL28B polymorphisms in T2D patients and healthy controls (HC). No association was found comparing the genotype and allele frequencies of both IL28B polymorphisms between T2D patients and HC. However, higher glucose levels were found in T2D patients carrying the IL28B CT/TT rs12979860 and GT/GG rs8099917 HCV risk genotypes compared to those with the protective CC and TT genotype (p=0.06 and p=0.02, respectively). Moreover, T2D patients with CT/TT rs12979860 HCV risk genotypes possessed significantly higher HbA1c levels than CC carriers (p=0.04). In conclusion, the IL28B HCV risk genotypes may influence glucose homeostasis in T2D patients without HCV. PMID- 27664842 TI - 14-bp ins/del polymorphism and +3142C>G SNP of the HLA-G gene have a significant impact on acute rejection after liver transplantation. AB - Expression of human leukocyte antigen G (HLA-G) has been associated with increased graft survival and decreased rejection episodes. It has been described that the HLA-G 14-base pair (bp) insertion/deletion (ins/del) (rs66554220) and +3142C>G (rs1063320) gene polymorphisms modify the expression level of HLA-G. The aim of the study was to investigate whether these HLA-G polymorphisms have an impact on acute rejection after liver transplantation. In total, 146 liver transplant recipients (57 with acute rejection and 89 without acute rejection) and 99 corresponding liver donors were genotyped for both polymorphisms. In liver transplantation the 14-bp ins/ins and the +3142GG genotypes are more frequent in recipients without rejection compared to recipients with rejection (3.5% vs. 31.5%, p=<0.001; 12.3% vs. 41.6%, p=<0.001) demonstrating an association with protection from acute rejection. In contrast, in liver donors we could not reveal an association. We conclude that 14-bp ins/ins and +3142GG genotypes of HLA-G in liver transplant recipients are of importance for prediction of acute rejection after liver transplantation. Thus genotyping of liver recipients for both polymorphisms might be useful to stratify liver transplant recipients according to the risk of acute liver transplant rejection. PMID- 27664843 TI - Antibodies against HLA-DP recognize broadly expressed epitopes. AB - HLA matching and avoidance of pre-transplant donor-specific antibodies are important in selection of donors for solid organ transplant. Solid phase testing with single antigen beads allows resolution of antibody reactivity to the level of the allele. Single antigen bead testing results at a large transplant center were reviewed to identify selective reactivity patterns of anti-HLA antibodies. Many HLA-DP antibodies were identified in the context of other HLA antibodies, but some sera had antibodies against only HLA-DP. B cell flow crossmatch testing was positive for 2 out of 9 sera with HLA-DP antibodies. Many patterns of reactivity corresponded to epitopes in hypervariable regions C and F of DPB1, but some matched epitopes in other regions or DPA1. Through analysis of single antigen bead testing from a large number of patients, we report that anti-HLA-DP antibodies predominantly recognize broadly cross-reactive epitopes. The United Network for Organ Sharing has mandated HLA-DP typing on all deceased kidney donors, and HLA-DP epitopes should be considered as the major antigens for avoidance of pre-transplant donor-specific antibodies. PMID- 27664844 TI - Age-specific differences in prognostic significance of rhythm conversion from initial non-shockable to shockable rhythm and subsequent shock delivery in out-of hospital cardiac arrest. AB - BACKGROUND: Early rhythm conversion from an initial non-shockable to a shockable rhythm and subsequent shock delivery in patients with out-of-hospital cardiac arrest (OHCA) has been associated with favourable neurological outcome (Cerebral Performance Category score 1 or 2; CPC 1-2). We hypothesized that the prognostic significance of rhythm conversion and subsequent shock delivery differs by age and time from initiation of cardiopulmonary resuscitation (CPR) by emergency medical service (EMS) providers to first defibrillation (shock delivery time). METHODS: We analysed 430,443 OHCA patients with an initial non-shockable rhythm using a prospective Japanese Utstein-style database from 2011 to 2014. The primary endpoint was 1-month CPC 1-2. RESULTS: Multivariate logistic regression revealed that rhythm conversion and subsequent shock delivery is positively associated with 1-month CPC 1-2: the adjusted odds ratio was 6.09 (95% confidence interval: 3.65-9.75) for shock delivery time <10min and 3.34 (2.58-4.27) for 10 19min in patients aged 18-64 years, and 3.16 (1.45-6.09) for <10min and 2.17 (1.51-3.03) for 10-19min in patients aged 65-74 years. However, it is negatively associated with 1-month CPC 1-2 for shock delivery time of 20-59min in patients aged 75-84 years (0.55; 0.27-0.98) and >=85 years (0.17; 0.03-0.53). CONCLUSIONS: Early rhythm conversion from an initial non-shockable to a shockable rhythm and subsequent shock delivery is associated with increased odds of 1-month CPC 1-2 in OHCA patients aged 18-74 years but not in those aged >=75 years. PMID- 27664845 TI - Large upper eyelid coloboma repair: a one-stage, one-site technique. AB - Current techniques for repairing large eyelid colobomas require preparation of other tissue sites and occasionally more than one procedure. We present a technique that requires only one procedure and is limited to the colobomatous eyelid; in addition, it is specifically designed to help avoid postoperative astigmatic and obstructive amblyopia. Outcomes are demonstrated in 3 cases of hemifacial microsomia. Large colobomas on the upper eyelid can be successfully and aesthetically repaired with only one procedure, incising only the congenitally abnormal eyelid. PMID- 27664846 TI - Progressive idiopathic tractional corectopia with iris thinning. AB - A 2-month-old boy presented with an irregular left pupil. Over the course of 3 months, progressive pupil ovalization, corectopia, and ballooning of the thinned superior iris tissue caused obstruction of the visual axis. Because of concern for deprivational amblyopia, a sectoral pupilloplasty and sphincterotomies were performed, restoring pupil shape and clearing the visual axis. On postoperative examinations, the pupil remained round, the visual axis clear, and visual acuity of the left eye improved. Findings and clinical course suggested the diagnosis of idiopathic tractional corectopia, a rare congenital disorder of unknown cause that may lead to isolated unilateral progressive corectopia and visual axis obstruction. Patients should receive regular follow-up examinations. PMID- 27664847 TI - Reply. PMID- 27664848 TI - Reply. PMID- 27664849 TI - Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study. AB - PURPOSE: The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment. METHODS: Using the SEARCH for Diabetes in Youth registry, we examined whether time from diabetes diagnosis to case registration differed by diabetes type, patient demographics, and the type of provider reporting the case to the study. Plots for time from diagnosis to registration were developed, and differences by key variables were examined using the log-rank test. RESULTS: Compared with time to registration for type 1 cases, it took 2.6 (95% confidence interval [CI], 2.5-2.6) times longer to register 50% of type 2 diabetes cases, and 2.3 (95% CI, 2.0-2.5) times longer to register 90% of type 2 cases. For type 1 diabetes cases, a longer time to registration was associated with older age, minority race/ethnicity, and cases, where the referring provider was not an endocrinologist. For type 2 diabetes cases, older age, non-Hispanic white race/ethnicity, and cases reported by providers other than an endocrinologist took longer to identify and register. CONCLUSIONS: These findings highlight the need for continued childhood diabetes surveillance to identify future trends and influences on changes in prevalence and incidence. PMID- 27664851 TI - Amyloid beta precursor protein regulates neuron survival and maturation in the adult mouse brain. AB - The amyloid-beta precursor protein (APP) is a transmembrane protein that is widely expressed within the central nervous system (CNS). While the pathogenic dysfunction of this protein has been extensively studied in the context of Alzheimer's disease, its normal function is poorly understood, and reports have often appeared contradictory. In this study we have examined the role of APP in regulating neurogenesis in the adult mouse brain by comparing neural stem cell proliferation, as well as new neuron number and morphology between APP knockout mice and C57bl6 controls. Short-term EdU administration revealed that the number of proliferating EdU+ neural progenitor cells and the number of PSA-NCAM+ neuroblasts produced in the SVZ and dentate gyrus were not affected by the life long absence of APP. However, by labelling newborn cells with EdU and then following their fate over-time, we determined that ~48% more newly generated EdU+ NeuN+ neurons accumulated in the granule cell layer of the olfactory bulb and ~57% more in the dentate gyrus of young adult APP knockout mice relative to C57bl6 controls. Furthermore, proportionally fewer of the adult-born olfactory bulb granule neurons were calretinin+. To determine whether APP was having an effect on neuronal maturation, we administered tamoxifen to young adult Nestin CreERT2::Rosa26-YFP and Nestin-CreERT2::Rosa26-YFP::APP-knockout mice, fluorescently labelling ~80% of newborn (EdU+) NeuN+ dentate granule neurons formed between P75 and P105. Our analysis of their morphology revealed that neurons added to the hippocampus of APP knockout mice have shorter dendritic arbors and only half the number of branch points as those generated in C57bl6 mice. We conclude that APP reduces the survival of newborn neurons in the olfactory bulb and hippocampus, but that it does not influence all neuronal subtypes equally. Additionally, APP influences dentate granule neuron maturation, acting as a robust regulator of dendritic extension and arborisation. PMID- 27664852 TI - Physico-chemical characteristics and primary structure of an affinity-purified alpha-D-galactose-specific, jacalin-related lectin from the latex of mulberry (Morus indica). AB - An alpha-D-galactose specific lectin belonging to the family of jacalin-related lectins (JRL) has been purified by affinity chromatography on cross-linked guar gum. Mass spectrometric data revealed that the protein harbors two chains like all the members of galactose-specific jacalin-related lectins (gJRL). De novo sequencing of proteolytic peptides demonstrated that the heavier chain consists of 133 amino acids and the lighter chain comprises of 21 or 24 amino acids. The heavier chain contains one N-glycosylation site (Asn47) occupied with either pauci-mannose type [GlcNAc2(Fuc)Man3(Xyl)] or complex type [GlcNAc2(Fuc)Man3(Xyl)GlcNAc(Fuc)Gal] N-glycans. Circular dichroism spectroscopy indicated that the secondary structure of the lectin is predominantly made up of beta-sheets, and differential scanning calorimetry revealed a thermal denaturation temperature of 77.6 degrees C. MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide) cell viability assays on MCF-7 and MDCK cells showed that the lectin is highly cytotoxic towards both cell lines when dosed at micromolar concentrations, suggesting that it may play a role in the defense mechanism of the plant. PMID- 27664850 TI - Birth weight was longitudinally associated with cardiometabolic risk markers in mid-adulthood. AB - PURPOSE: Birth weight (BW) is associated with risk of cardiovascular (CV) disease. The findings from studies examined the association of BW with metabolic markers of CV risk were inconsistent and controversial. We examined the association of BW with insulin resistance and blood lipids using repeated measures up to mid-adulthood. METHODS: Data from seven screenings of the Bogalusa Heart Study-a longitudinal study of cardiovascular risk factors in Bogalusa, LA are analyzed using generalized estimation equations method. Participants with birth data and at least one measurement of study outcomes between 18 and 44 years (n = 2,034) were included. RESULTS: BW is inversely associated with insulin resistance, triglycerides, and total cholesterol (P < .01 for all). For 1-kg decrease in BW, insulin resistance increased by 2.3 units, 95% confidence interval (CI) = 0.7-3.9; triglycerides by 8.7 mg per dL, 95% CI = 4.9-12.4, and total cholesterol by 5.4 mg per dL, 95% CI = 1.8-9.1. The association of body mass with adult blood lipids levels is weaker in persons with low versus normal BW. CONCLUSIONS: The study provides strong evidence of an inverse relationship of BW with adulthood cardiometabolic risk profile. Persons born with low BW are maybe less responsive to preventive interventions aiming at weight reduction. PMID- 27664853 TI - IinQ attenuates systemic inflammatory responses via selectively impairing the Myddosome complex formation upon TLR4 ligation. AB - A specific small-molecule inhibitor of the TLR4 signaling complex upstream of the IKK would likely provide therapeutic benefit for NF-kappaB-mediated inflammatory disease. We previously identified brazilin as a selective upstream IKK inhibitor targeting the Myddosome complex. In this study, using a cell-based ubiquitination assay for IRAK1 and a chemical library comprising a series of structural analogues of brazilin, a novel small molecule, 2-hydroxy-5,6-dihydroisoindolo[1,2 a]isoquinoline-3,8-dione (IinQ), was identified as a selective and potent inhibitor of IRAK1-dependent NF-kappaB activation upon TLR4 ligation. In RAW264.7 macrophages, IinQ drastically suppressed activation of upstream IKK signaling events including membrane-bound IRAK1 ubiquitination and IKK phosphorylation by the TLR4 ligand, resulting in reduced expression of proinflammatory mediators including IL-6, TNF-alpha, and nitric oxide. Interestingly, IinQ did not suppress NF-kappaB activation via the TLR3 ligand, DNA damaging agents, or a protein kinase C activator, indicating IinQ is specific for TLR4 signaling. Analysis of upstream signaling events further confirmed that IinQ disrupts the MyD88-IRAK1 TRAF6 complex formation induced by LPS treatment, without affecting TLR4 oligomerization. Moreover, intravenous administration of IinQ significantly reduced lethality and attenuated systemic inflammatory responses in an in vivo mouse model of endotoxin shock following LPS challenge. Thus, IinQ represents a novel class of brazilin analogues with improved potency and specificity toward disruption of Myddosome complex formation in TLR4 signaling, indicating that IinQ may be a promising therapeutic candidate for the treatment of systemic inflammatory diseases. PMID- 27664854 TI - Standardization of the homogeneous mobility shift assay protocol for evaluation of anti-infliximab antibodies. Application of the method to Crohn's disease patients treated with infliximab. AB - BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (?1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug. PMID- 27664856 TI - Lethal Necrotizing Cellulitis Caused by ESBL-Producing E. Coli after Laparoscopic Intestinal Vaginoplasty. AB - BACKGROUND: The absence of a functional vagina has a negative effect on the quality of life of women. Multiple surgical procedures have been described for vaginal reconstruction in these patients. CASE: We present a case of an 18-year old transgender woman, who underwent laparoscopic intestinal vaginoplasty as vaginal reconstruction, and subsequently developed septic shock and multiple organ failure on the basis of an extended-spectrum beta-lactamase-producing Escherichia coli. A severe progression of the necrotizing fasciitis was lethal, despite repeated surgical debridement, intravenous antibiotic use, and supportive care at the intensive care unit. SUMMARY AND CONCLUSION: Although vaginal reconstruction has a positive influence on the quality of life in transgender women, physicians and patients need to be aware of serious complications that might arise. PMID- 27664855 TI - Comparative analysis of the anti-chikungunya virus activity of novel bryostatin analogs confirms the existence of a PKC-independent mechanism. AB - Previously, we reported that salicylate-based analogs of bryostatin protect cells from chikungunya virus (CHIKV)-induced cell death. Interestingly, 'capping' the hydroxyl group at C26 of a lead bryostatin analog, a position known to be crucial for binding to and modulation of protein kinase C (PKC), did not abrogate the anti-CHIKV activity of the scaffold, putatively indicating the involvement of a pathway independent of PKC. The work detailed in this study demonstrates that salicylate-derived analog 1 and two capped analogs (2 and 3) are not merely cytoprotective compounds, but act as selective and specific inhibitors of CHIKV replication. Further, a detailed comparative analysis of the effect of the non capped versus the two capped analogs revealed that compound 1 acts both at early and late stages in the chikungunya virus replication cycle, while the capped analogs only interfere with a later stage process. Co-dosing with the PKC inhibitors sotrastaurin and Go6976 counteracts the antiviral activity of compound 1 without affecting that of capped analogs 2 and 3, providing further evidence that the latter elicit their anti-CHIKV activity independently of PKC. Remarkably, treatment of CHIKV-infected cells with a combination of compound 1 and a capped analog resulted in a pronounced synergistic antiviral effect. Thus, these salicylate-based bryostatin analogs can inhibit CHIKV replication through a novel, yet still elusive, non-PKC dependent pathway. PMID- 27664857 TI - Determining antigen specificity of a monoclonal antibody using genome-scale CRISPR-Cas9 knockout library. AB - An essential step in monoclonal antibody (mAb) development is the characterization and final identification of the specific target antigen and its epitope. Antibody validation is rather straightforward when immunization is carried out with peptide or purified protein, but is more difficult when whole cells or other complex antigens are used for the immunization. Determining antigen specificity of a mAb is further complicated, when reactivity of an antibody is not detected in Western blotting and/or immunoprecipitation assay. In addition to protein-based methods used for antibody characterization, a number of gene-based techniques, such as cDNA expression or short-interfering RNA (siRNA) knockdown have been applied for validation of antibodies with restricted reactivities. Earlier we have generated, characterized, but not identified the BF4 mAb that specifically stains viral biofilms on the surface of the Human T lymphotropic Virus Type I (HTLV-1) infected T cells. In this study, using the recently developed genome-scale CRISPR-Cas9 knockout (GeCKO) library vectors, we have established the CEM T- and the Raji B cell lines with pooled libraries. After immunofluorescent staining of these cells, negative cell sorting, and guide RNA (gRNA) sequencing, we have identified BF4 as an anti-CD82 mAb. A deep sequence analysis of GeCKO library transferred to the cells shows that the chance to succeed in the selection of antibody-negative cells and, therefore, to identify a mAb depends on the quality of cell library preparation. We believe that the described method is applicable for identification of many other hybridomas and represents a good alternative to the current protein- and gene based methods used for mAb validation. PMID- 27664858 TI - Old chemotherapy makes a comeback: dual alkylator therapy for pediatric high grade glioma. PMID- 27664866 TI - Nivolumab-Induced Colitis Treated by Infliximab. PMID- 27664860 TI - Tumor treating fields: a novel treatment modality and its use in brain tumors. AB - Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM. TTFields are continuously delivered by 4 transducer arrays consisting each of 9 insulated electrodes that are placed on the patient's shaved scalp and connected to a portable device. Here we summarize the preclinical data and mechanism of action, the available clinical data, and further outlook of this treatment modality in brain tumors and other cancer indications. PMID- 27664867 TI - Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance. AB - Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. PMID- 27664868 TI - Electroacupuncture alleviates nerve injury after cerebra ischemia in rats through inhibiting cell apoptosis and changing the balance of MMP-9/TIMP-1 expression. AB - Accumulating evidence demonstrates that acupuncture and electroacupuncture (EA) can exert a neuroprotective role for cerebral ischemia, but their precise mechanism remains largely unknown. Therefore, in this study, the effects of EA stimulation on cerebral ischemia reperfusion and its neuroprotective mechanisms were investigated. A rat model of middle cerebral artery occlusion (MCAO) was developed, and EA stimulation (2Hz, 1mA) at Baihui and Siguan acupoints was applied 30min after MCAO and then once daily for 7 consecutive days. The results indicated that EA stimulation significantly reduced the cerebral infarct area and neurological deficit scores, decreased the number of apoptotic cells, up regulated Bcl-2 protein expression, and down-regulated Bax protein expression. EA stimulation resulted in a significant increase of proliferative cells in the cerebral tissues. Additionally, EA stimulation significantly down-regulated the expression levels of matrix metalloproteinase -9 (MMP-9) mRNA and protein, and simultaneously up-regulated the expression levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA and protein, which resulted in an imbalance of MMP-9/TIMP-1expression, although it did not significantly change MMP-2 and TIMP-2 expression. These findings indicate that EA stimulation at Baihui and Siguan acupoints exerts a neuroprotective role against cerebral ischemia-reperfusion injury, which is probably associated with the inhibition of apoptosis and altering the balance of MMP-9/TIMP-1 expression. PMID- 27664869 TI - Development of a 20-MHz wide-bandwidth PMN-PT single crystal phased-array ultrasound transducer. AB - In this study, a 20-MHz 64-element phased-array ultrasound transducer with a one wavelength pitch is developed using a PMN-30%PT single crystal and double matching layer scheme. High piezoelectric (d33>1000pC/N) and electromechanical coupling (k33>0.8) properties of the single crystal with an optimized fabrication process involving the photolithography technique have been demonstrated to be suitable for wide-bandwidth (?70%) and high-sensitivity (insertion loss ?30dB) phased-array transducer application. A -6dBbandwidth of 91% and an insertion loss of 29dBfor the 20-MHz 64-element phased-array transducer were achieved. This result shows that the bandwidth is improved comparing with the investigated high frequency (?20MHz) ultrasound transducers using piezoelectric ceramic and single crystal materials. It shows that this phased-array transducer has potential to improve the resolution of biomedical imaging, theoretically. Based on the hypothesis of resolution improvement, this phased-array transducer is capable for small animal (i.e. mouse and zebrafish) studies. PMID- 27664870 TI - Draft genome sequence of a CTX-M-15-producing Klebsiella pneumoniae sequence type 340 (clonal complex 258) isolate from a food-producing animal. AB - Klebsiella pneumoniae carrying blaCTX-M-15 have been widely disseminated in hospital settings. In this regard, most clinically important strains belong to clonal complex 28 (CC258), which includes sequence type 340 (ST340). In this study, we present the draft genome sequence of a CTX-M-15-producing ST340 K. pneumoniae strain isolated from a food-producing animal in Brazil. PMID- 27664871 TI - Insurance status and race affect treatment and outcome of traumatic brain injury. AB - BACKGROUND: There is increasing evidence that race and socioeconomic factors affect patient outcomes after traumatic brain injury (TBI). Our goal was to assess the effect of race, ethnicity and insurance status on hospital length of stay, procedures performed, mortality, and discharge disposition after TBI. METHODS: This was a retrospective cohort study using the National Trauma Data Bank (2002-2012) to analyze patients aged 14-89 y with one of five closed head injuries. Univariate regressions identified demographic and injury characteristics that were significant predictors of outcomes. These variables were then included in multivariate regression models. RESULTS: We analyzed 187,354 TBI patients. The sample was 78% white, 9% black, 9% Hispanic, 3% Asian, and 1% native American, and included 42% Medicare, 30% private insurance, 12% uninsured, 8% other insurance, and 8% Medicaid. Compared with white patients, black and Hispanic patients were more likely to have a TBI procedure (blacks odds ratio [OR] = 1.19, P < 0.001; Hispanics OR = 1.33, P < 0.001), had longer hospital stays (blacks coeff = 1.02, P < 0.001; Hispanics coeff = 0.61, P < 0.001), were less likely to die in the hospital (blacks OR = 0.90, P = 0.006; Hispanics OR = 0.90, P = 0.007), and more (black OR = 1.09, P = 0.001) or less likely (Hispanic OR = 0.76, P < 0.001) to be discharged to rehabilitation. Compared with the privately insured, the uninsured were less likely to have a TBI procedure (OR = 0.90, P = 0.001), had longer hospital stays (coeff = 0.24, P < 0.001), were more likely to die in the hospital (OR = 1.37, P < 0.001), and less likely to be discharged to rehabilitation (OR = 0.53, P < 0.001). CONCLUSIONS: Race/ethnicity and insurance status significantly affect TBI patient outcomes, even after controlling for demographic and injury characteristics. PMID- 27664872 TI - Early endocrine attending surgeon presence increases operating room efficiency. AB - BACKGROUND: Preincision operating room (OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency, and decreasing cost. METHODS: Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/min of OR time was $54. Patients classified as in the OR <=10 min before attending arrival or >10 min before attending arrival. RESULTS: A total of 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 mo. Of the patients, 128 were in the OR <=10 min before attending arrival, and 99 patients were >10 min (3 +/- 3 min versus 35 +/- 14 min, P < 0.01). The <=10 min procedures started sooner after patient arrival in OR (40 +/- 11 versus 63 +/- 19, P < 0.01) which equated to $1202 of savings before incision. Although attending time in the OR before incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the <=10 min groups, saving $2416 +/- 477 and $1458 +/- 244, respectively (P < 0.01). Attending time in OR before thyroidectomy was 13 min longer in <=10 min than >10 min (P < 0.01), but incisions were made 20 min sooner (P < 0.01) equating to $1076 +/- 120 in savings. CONCLUSIONS: Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings. PMID- 27664873 TI - The identification of risk factors for venous thromboembolism in gastrointestinal oncologic surgery. AB - BACKGROUND: The aim of this study was to examine the incidence and factors associated with occurrence of venous thromboembolism (VTE) in patients undergoing major gastrointestinal (GI) surgery for malignancy. METHODS: The American College of Surgeon's National Surgical Quality Improvement Program, Participant User File database was queried from 2005 to 2012 to study major GI operations performed for cancer. Predictors of VTE and their relation to survival were studied. RESULTS: In 79,300 patients, the incidence of deep venous thrombosis was 1.7%, and pulmonary embolism was 0.9% during the 30-d postoperative period. The highest rate of VTE occurred after esophagectomy (5.9%) followed by pancreatectomy (3.2%), hepatectomy (3.2%), gastrectomy (2.5%), enterectomy (2.3%), colectomy, and proctectomy (2.0%). On multivariate analysis, disseminated cancer, age >= 80 y, body mass index > 35 kg/m(2), functional status, post operative sepsis, pulmonary dysfunction, and longer operative time were associated with occurrence of VTE. Occurrence of VTE was associated with mortality on multivariate analysis (odds ratio 2.4, 95% confidence interval 2.0-3.0, P < 0.001). CONCLUSIONS: Absolute incidence of VTE after major GI surgery is low but is associated with significant mortality and postoperative complications. Disseminated cancer, post operative sepsis, longer operative time, and increased body mass index >35 kg/m(2) further increased the risk of VTE in patients undergoing surgery for malignancy. Surveillance strategies should be implemented for those cancer patients who have multiple risk factors for VTE. PMID- 27664874 TI - A laparoscopic technique of partial hepatectomy in the rat. AB - BACKGROUND: Laparoscopic partial hepatectomy is an increasingly applied technique in the treatment of liver tumors and in living donor transplantation. There is a need for establishing an animal model that would facilitate experimental research on the technique. The aim of the present study was to describe a safe and efficient laparoscopic technique of 70% partial hepatectomy in the rat. MATERIALS AND METHODS: Twenty-four male Wistar rats underwent either laparoscopic (group LAP-HEP) or open resection of the median and left lateral hepatic lobes (group HEP). In group LAP-HEP, a 5-mm Hg pneumoperitoneum was established. Three 5-mm trocars were introduced in the abdominal cavity. A self-made pretied ligature loop was used to ligate en bloc the pedicles of the hepatic lobes to be resected. A self-made sterile elastic specimen retrieval bag facilitated extraction of the resected liver tissue. In group HEP, the same liver lobes were resected by ligation of their pedicles after midline laparotomy. RESULTS: The percentage of resected liver parenchyma did not differ between groups. All animals returned to normal feeding activity by 48 h postoperation and had no complications. CONCLUSIONS: A simple, cost-effective, safe, and efficient laparoscopic technique for 70% partial hepatectomy in the rat was described. PMID- 27664875 TI - Ex-vivo oxygenated perfusion of free flaps during ischemia time: a feasibility study in a porcine model and preliminary results. AB - BACKGROUND: Under ideal circumstances, creation of the anastomosis during free flap transfer is a routine task and can be performed under short ischemia time. However, vessels may be in suboptimal state due to atherosclerosis, radiotherapy or trauma, increasing difficulties regarding receptor vessel identification, and anastomosis which in turn may lead to lengthening of ischemia time resulting in postoperative wound problems or even flap loss. In the current pilot study, a modified heart-lung machine was assembled to achieve continuous oxygenated extracoporeal perfusion using porcine myocutaneous rectus abdominis flaps, aimed at minimizing tissue damage occurring during ischemia time. MATERIALS AND METHODS: Different pilot test groups with n = 2 were created, including oxygenated perfusion with heparinized autologous blood or organ preservation solutions. Control groups included short flush with preservation solution followed by cold storage. RESULTS: Flaps were successfully attached to the modified heart-lung machine while maintaining stable flow throughout the 24-h experiments. Flaps undergoing continuous oxygenated perfusion with preservation solutions showed minimal or no signs of cell necrosis during the 24-h experiment, in contrast to using heparinized autologous blood or flushing and cold storage. CONCLUSIONS: The use of a modified heart-lung machine for oxygenated perfusion of free flaps provides new possibilities to minimize tissue damage during ischemia time, and further study of its use is warranted. PMID- 27664877 TI - Evaluating the effectiveness of a mock oral educational program. AB - BACKGROUND: To obtain board certification, the American Board of Surgery requires graduates of general surgery training programs to pass both the written qualifying examination (QE) and the oral certifying examination (CE). In 2015, the pass rates for the QE and CE were 80% and 77%, respectively. In the 2011-2012 academic year, the University of Wisconsin instituted a mandatory, faculty-led, monthly CE preparation educational program (CE prep) as a supplement to their existing annual mock oral examination. We hypothesized that the implementation of these sessions would improve the first-time pass rate for residents taking the ABS CE at our institution. Secondary outcomes studied were QE pass rate, correlation with American Board of Surgery In-Training Examination (ABSITE) and mock oral examination scores, cost, and type of study materials used, perception of examination difficulty, and applicant preparedness. METHODS: A sixteen question survey was sent to 57 of 59 residents who attended the University of Wisconsin between the years of 2007 and 2015. Email addresses for two former residents could not be located. De-identified data for the ABSITE and first-time pass rates for the QE and CE examination were retrospectively collected and analyzed along with survey results. Statistical analysis was performed using SPSS version 22 (IBM Corp., Armonk, NY). P values < 0.05 were considered significant. RESULTS: Survey response rate was 77.2%. Of the residents who have attempted the CE, first-time pass rate was 76.0% (19 of 25) before the implementation of the formal CE Prep and 100% (22 of 22) after (P = 0.025). Absolute ABSITE score, and mock oral annual examination grades were significantly improved after the CE Prep was initiated (P values < 0.001 and 0.003, respectively), however, ABSITE percentile was not significantly different (P = 0.415). ABSITE raw score and percentile, as well as mock oral annual examination scores were significantly associated with passing the QE (0.032, 0.027, and 0.020, respectively), whereas mock oral annual examination scores alone were associated with passing the CE (P = 0.001). Survey results showed that residents perceived the CE to be easier than the annual mock oral after the institution of the CE prep course (P = 0.036), however, there was no difference in their perception of preparedness. Overall, applicants felt extremely prepared for the CE (4.70 +/- 0.5, Likert scale 1-5). CONCLUSIONS: Formal educational programs instituted during residency can improve resident performance on the ABS certifying examination. The institution of a formal, faculty-led monthly CE preparation educational program at the University of Wisconsin has significantly improved the first-time pass rate for the ABS CE. Mock oral annual examination scores were also significantly improved. Furthermore, ABSITE scores correlate with QE pass rates, and mock oral annual examination scores correlate with pass rates for both QE and CE. PMID- 27664876 TI - Barriers to efficiency in robotic surgery: the resident effect. AB - BACKGROUND: Robotic surgery offers advantages over conventional operative approaches but may also be associated with higher costs and additional risks. Analyzing surgical flow disruptions (FDs), defined as "deviations from the natural progression of an operation," can help target training techniques and identify opportunities for improvement. MATERIALS AND METHODS: Thirty-two robotic surgery operations were observed over a 6-wk period at one 900-bed surgical center. FDs were recorded in detail and classified into one of 11 different categories. Procedure type, robot model, and resident involvement were also recorded. Linear regression analyses were used to evaluate the effects of these parameters on FDs and operative duration. RESULTS: Twenty-one prostatectomies, eight sacrocolpopexies, and three nephrectomies were observed. The mean number of FDs was 48.2 (95% confidence interval [CI] 38.6-54.8 FDs), and mean operative duration was 163 min (95% CI 148-179 min). Each FD added 2.4 min (P = 0.025) to a case's total operative duration. The number and rate of FDs were significantly affected by resident involvement (P = 0.008 and P = 0.006, respectively). Resident cases demonstrated mostly training, equipment, and robot switch FDs, whereas nonresident cases demonstrated mostly equipment, instrument changes, and external factor FDs. CONCLUSIONS: Although the FDs encountered in resident training are more frequent, they may not significantly increase operative duration. Other FDs, such as equipment or external factors, may be more impactful. Limiting these specific FDs should be the focus of performance improvement efforts. PMID- 27664878 TI - Innate lymphoid cells: a paradigm for low SSI in cleft lip repair. AB - BACKGROUND: Cleft lip and palate reconstructions demonstrate significantly lower surgical site infection rates compared with clean-contaminated cases, prompting investigation into the pathophysiology causing this discrepancy. Recent studies have identified a new group of innate lymphocytes called innate lymphoid cells (ILCs), located in barrier surfaces of the skin, airways, and intestine. Our objectives were to explore for the first time the presence of ILCs in the vermillion of neonates and young children undergoing cleft lip reconstruction and characterize their composition by measuring the three classes of ILCs. MATERIALS AND METHODS: Lip tissue samples were collected from 13 subjects undergoing vermillion resection during cleft lip reconstructive surgery. Preparative, transmission electron microscopy, and analytical flow cytometry were performed. The functionality of ILCs was tested in terms of their capacity to produce type 1 (IFN-gamma/TNF-alpha), type 2 (IL-5/IL-13), and type 3 (IL-17/IL-22) cytokines. Data were analyzed using Student t test or the analysis of variance to establish significance (P < 0.05) among groups for all other data. RESULTS: All three classes of ILCs were detected and visualized in the tissue samples. In all samples, the level of ILC2 subset was significantly higher than the other two ILC subsets (P < 0.01), followed by the ILC1 subset, which was present in significantly higher levels than the ILC3 subset (P < 0.05). CONCLUSIONS: Our data place ILCs for the first time in the interface of oral mucosal immunity, tissue microenvironment, and homeostasis during and after tissue development, possibly explaining lower infection rates in cleft lip or palate reconstructions. PMID- 27664879 TI - Readmission after major surgery: effect of the postdischarge environment. AB - BACKGROUND: Although uncoordinated postdischarge care has been associated with poor clinical outcomes, the effect of discharge to a low healthcare resource area (LHRA) on readmission remains undetermined. We sought to assess how the quality of discharge area health resources impact readmission following major surgery. METHODS: This cross-sectional study was performed by linking Maryland state data for 2012-2015 to the Agency for Healthcare Research and Quality Area Health Resource File. Patients undergoing one of 11 common surgical procedures were identified. Multivariable logistic regression was performed to assess the effect of discharge area health resource quality on readmission. RESULTS: A total of 76,747 patients were identified of which 9.4% were discharged to a high healthcare resource area (HHRA), whereas 81.9% of patients were discharged to an LHRA. Perioperative morbidity and length of stay were comparable between HHRA versus LHRA patients (both P > 0.05). Among all patients, 30-d and 90-d readmission was 6.5% and 12.4%, respectively. On multivariable analysis, discharge to LHRA was independently associated with a 19% (odds ratio = 1.19; 95% CI, 1.01-1.41; P = 0.043) and 18% (odds ratio = 1.18; 95% CI, 1.04-1.33; P = 0.010) greater odds of 30-d and 90-day readmission, respectively. CONCLUSIONS: Patients discharged to an area characterized by LHRA were more likely to be readmitted at 30 d and 90 d following index discharge. PMID- 27664880 TI - Prophylactic versus symptomatic Ladd procedures for pediatric malrotation. AB - BACKGROUND: Intestinal malrotation can lead to volvulus resulting in necrosis, sepsis, and death. For symptomatic patients, treatment includes the Ladd procedure. However, debate remains regarding the timing and need for intervention for asymptomatic infants. We evaluated our experience with Ladd procedures including a clinical practice of prophylactic surgery for asymptomatic patients. MATERIALS AND METHODS: A retrospective review of pediatric patients undergoing the Ladd procedure was performed. Prophylactic Ladd procedures were identified as those occurring before any malrotation-related symptoms. Results were analyzed with student t test, Mann-Whitney U, and chi-squared tests. RESULTS: From 2011 2014, 42 patients (prophylactic = 19, symptomatic = 23) underwent the Ladd procedure. The median age (IQR, interquartile range) of patients was 9.6 (3.9-18) mo and 18 (2.4-52) mo for prophylactic and symptomatic patients, respectively (P = 0.38). In patients who underwent symptomatic Ladd procedures, nine (39%) had volvulus and one (4.3%) had bowel necrosis at time of surgery. No prophylactic Ladd procedure patients required reoperation, whereas six (26%) symptomatic patients required malrotation-related reoperations (P = 0.02). Median (IQR) days to full enteral feeds were 5.0 d (3.3-6.8) versus 7.4 (5.0-11; P = 0.11), whereas median days to discharge were 8.0 d (6.1-11) versus 11 d (7.5-32) until discharge (P = 0.09) for prophylactic and symptomatic patients, respectively. CONCLUSIONS: Although symptomatic patients represent sicker children, the postoperative complications appear to be higher. For infants with known malrotation, prophylactic operations may be beneficial and should be considered. A larger, prospective study to demonstrate effectiveness and generalizability for prophylactic Ladd procedure is warranted. PMID- 27664881 TI - Postoperative acute care use after freestanding ambulatory surgery. AB - BACKGROUND: Surgical procedures in the United States are increasingly performed in the ambulatory setting, including freestanding ambulatory surgery centers (ASCs). However, there is a lack of research and tracking of surgical outcomes in this setting. MATERIALS AND METHODS: We analyzed data from a state all-payer claims database to produce a retrospective cohort study on the rate of acute care use (emergency department [ED] visits and inpatient admissions) within 7 d after operations performed in freestanding ASCs in South Carolina. Two-level reliability-adjusted generalized linear mixed models accounting for random facility-level effects were used to adjust for patient-level and facility-level characteristics. RESULTS: A total of 1,328,708 procedures were performed in 86 freestanding ASCs in South Carolina from 2006-2013. The overall rate of postoperative acute care per 1000 procedures within 7 d was 17.3 (95% confidence interval [CI], 15.3-19.5). Patient characteristics associated with the highest postoperative acute care use within 7 d included Medicaid insurance (adjusted odds ratio [aOR], 1.79; 95% CI, 1.70-1.90), lowest median household income (aOR, 1.36; 95% CI, 1.30-1.43), and preoperative Charlson Comorbidity Index (CCI) score 3+ (aOR, 4.14; 95% CI, 3.95-4.34). Total charges for postoperative ED visits (n = 14,682) and inpatient admissions (n = 8945) within 7 d were approximately $51.4 and $361.1 million, respectively from 2006-2013. CONCLUSIONS: Acute care use within 7 d was commonly >=10 per 1000 procedures performed in freestanding ASCs in South Carolina. These measures may be targets for quality and cost improvement and innovation. Patients at risk for acute care utilization may benefit from improvements in postoperative follow-up after procedures in ASCs. PMID- 27664882 TI - The effect of ionized collagen for preventing postoperative adhesion. AB - BACKGROUND: Collagen exhibits ideal multifactorial action for preventing tissue adhesions. This study examined the efficacy of ionized collagen in preventing tissue adhesion after surgical procedures. MATERIALS AND METHOD: Ionized collagen was prepared using the esterification technique of natural collagen. Three forms of collagen materials (membrane, film, and gel) were compared with three commercialized materials (oxidized regenerated cellulose membrane [OC membrane], hyaluronic acid and carboxymethylcellulose film, and gel [HC film and HC gel]) in a rat cecum abrasion model. Antiadhesive activity and histologic findings were assessed. RESULT: The incidence of adhesion was reduced significantly in all test groups compared to the sham-operated control group (100% in control, 14.3% in collagen membrane, 63.6% in collagen film, 25.0% in collagen gel, 55.6% in OC membrane, 75% in HC film, and 83.3% in HC gel). All collagen materials of the three forms exhibited a significant reduction in adhesion grade compared with the sham operation, whereas no significant difference was found among these three different forms. The collagen membrane showed significantly less adhesion grade, less inflammation and more regenerative features compared to widely used conventional materials. CONCLUSIONS: This preclinical investigation indicated that ionized collagen materials readily formed clinically suitable shapes for easy handling without the need for any complex processing and effectively reduced postoperative tissue adhesion profiles compared to conventional antiadhesive agents. PMID- 27664884 TI - Effects of Myrtus communis extract treatment in bile duct ligated rats. AB - BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-alpha, and interleukin-1beta measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-alpha, and interleukin-1beta levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration. PMID- 27664883 TI - Global microRNA profiling for diagnostic appraisal of melanocytic Spitz tumors. AB - BACKGROUND: Melanoma skin cancer remains the leading cause of skin cancer-related deaths. Spitz lesions represent a subset of melanocytic skin lesions characterized by epithelioid or spindled melanocytes organized in nests. These lesions occupy a spectrum ranging from benign Spitz and atypical Spitz lesions all the way to malignant Spitz tumors. Appropriate management is reliant on accurate diagnostic classification, yet this effort remains challenging using current light microscopic techniques. The discovery of novel biomarkers such as microRNAs (miR) may ultimately be a useful diagnostic adjunct for the evaluation of Spitz lesions. miR expression profiles have been suggested for non-Spitz melanomas but have yet to be ascribed to Spitz lesions. We hypothesized that distinct miR expression profiles would be associated with different lesions along the Spitz spectrum. MATERIALS AND METHODS: RNAs extracted from paraffin-embedded, formalin-fixed tissues of 11 resected skin lesions including benign nevi (n = 2), benign Spitz lesions (n = 3), atypical Spitz lesions (n = 3), and malignant Spitz tumors (n = 3) were analyzed by the NanoString platform for simultaneous evaluation of over 800 miRs in each patient sample. RESULTS: Benign Spitz lesions had increased expression of miR-21-5p and miR-363-3p compared with those of benign nevi. Malignant Spitz lesions exhibited overexpression of miR-21-5p, miR 155-5p, and miR-1283 relative to both benign nevi and benign Spitz tumors. Notably, atypical Spitz tumors had increased expression of miR-451a and decreased expression of miR-155-5p expression relative to malignant Spitz lesions. Conversely, atypical Spitz lesions had increased expression of miR-21-5p, miR-34a 5p, miR-451a, miR-1283, and miR-1260a relative to benign Spitz tumors. CONCLUSIONS: Overall, distinct miR profiles are suggested among Spitz lesions of varying malignant potential with some similarities to non-Spitz melanoma tumors. This work demonstrates the feasibility of this analytic method and forms the basis for further validation studies. PMID- 27664886 TI - Assessing surgeon behavior change after anastomotic leak in colorectal surgery. AB - BACKGROUND: Recency effect suggests that people disproportionately value events from the immediate past when making decisions, but the extent of this impact on surgeons' decisions is unknown. This study evaluates for recency effect in surgeons by examining use of preventative leak testing before and after colorectal operations with anastomotic leaks. MATERIALS AND METHODS: Prospective cohort of adult patients (>=18 y) undergoing elective colorectal operations at Washington State hospitals participating in the Surgical Care and Outcomes Assessment Program (2006-2013). The main outcome measure was surgeons' change in leak testing from 6 mo before to 6 mo after an anastomotic leak occurred. RESULTS: Across 4854 elective colorectal operations performed by 282 surgeons at 44 hospitals, there was a leak rate of 2.6% (n = 124). The 40 leaks (32%) in which the anastomosis was not tested occurred across 25 surgeons. While the ability to detect an overall difference in use of leak testing was limited by small sample size, nine (36%) of 25 surgeons increased their leak testing by 5% points or more after leaks in cases where the anastomosis was not tested. Surgeons who increased their leak testing more frequently performed operations for diverticulitis (45% versus 33%), more frequently began their cases laparoscopically (65% versus 37%), and had longer mean operative times (195 +/- 99 versus 148 +/- 87 min), all P < 0.001. CONCLUSIONS: Recency effect was demonstrated by only one-third of eligible surgeons. Understanding the extent to which clinical decisions may be influenced by recency effect may be important in crafting quality improvement initiatives that require clinician behavior change. PMID- 27664887 TI - Prognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection. AB - BACKGROUND: Although preoperative carcinoembryonic antigen (pre-CEA) and carbohydrate antigen 19-9 (pre-CA 19-9) are reportedly prognostic indicators for colorectal cancer (CRC), the prognostic roles of postoperative CEA (post-CEA) and CA 19-9 (post-CA 19-9) shortly after surgery have not been clarified in patients with curatively resected stage IV CRC. The aim of this study was to evaluate the predictive abilities of post-CEA and post-CA 19-9. METHODS: A total of 129 consecutive patients who had stage IV CRC and underwent R0 resection were retrospectively analyzed. Pre-CEA and post-CEA and CA 19-9 levels were measured within 1 mo before and 3 mo after surgery, respectively. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Pre-CEA was elevated (>=5.0 ng/mL) in 73.6% of the patients and remained elevated after surgery in 32.7% of the patients. Elevated post-CA 19-9 (>=50 U/mL) was observed in 9.5% of the patients. Neither elevated pre-CEA nor elevated pre-CA 19-9 was significantly associated with RFS but both elevated post-CEA and elevated post-CA 19-9 were associated with markedly reduced RFS (P = 0.0002 and P = 0.0004, respectively). When considered in combination, post-CEA and post-CA 19 9 significantly stratified RFS and was an independent predictive factor for recurrence (P = 0.0035), as was lymphatic invasion (P = 0.0015). Post-CA 19-9 was the only evident independent predictive factor for overall survival (P = 0.0336). CONCLUSIONS: In patients with stage IV CRC who underwent curative resection, the combination of post-CEA and post-CA 19-9 at 3 mo after surgery was a potent prognostic indicator for recurrence. PMID- 27664885 TI - Age and preexisting conditions as risk factors for severe adverse events and failure to rescue after injury. AB - BACKGROUND: Failure to rescue (FTR: the conditional probability of death after complication) has been studied in trauma cohorts, but the impact of age and preexisting conditions (PECs) on risk of FTR is not well known. We assessed the relationship between age and PECs on the risk of experiencing serious adverse events (SAEs) subsequent FTR in trauma patients with the hypothesis that increased comorbidity burden and age would be associated with increased FTR. MATERIALS AND METHODS: We performed a retrospective cohort analysis at an urban level 1 trauma center in Pennsylvania. All patients aged >=16 y with minimum Abbreviated Injury Scale score >=2 from 2009 to 2013 were included. Univariate logistic regression models for SAE and FTR were developed using age, PECs, demographics, and injury physiology. Variables found to be associated with the end point of interest (P <= 0.2) in univariate analysis were included in separate multivariable logistic regression models for each outcome. RESULTS: SAE occurred in 1136 of 7533 (15.1 %) patients meeting inclusion criteria (median age 42 [interquartile range 26-59], 53% African-American, 72% male, 79% blunt, median ISS 10 [interquartile range 5-17]). Of those who experienced an SAE, 129 of 1136 patients subsequently died (FTR = 11.4%). Development of SAE and FTR was associated with age >= 70 y (odds ratio 1.58-1.78, 95% confidence interval 1.13 2.82). Renal disease was the only preexisting condition associated with both SAE and FTR. CONCLUSIONS: Trauma patients with renal disease are mostly at increased risk for both SAE and FTR, but other PECs associated with SAE are not necessarily those associated with FTR. Future interventions designed to reduce FTR events should target this high-risk cohort. PMID- 27664888 TI - Frozen section analysis in the post-Bethesda era. AB - BACKGROUND: The utility of frozen section (FS) for indeterminate thyroid nodules is controversial. In 2009, the Bethesda System for Reporting Thyroid Cytopathology was established to further subcategorize indeterminate fine-needle aspiration results (follicular lesions, FL) into Bethesda category 3 (BC3) and Bethesda category 4 (BC4). We hypothesize that FS will have less utility in the evaluation of BC3 lesions when compared to BC4. MATERIALS AND METHODS: A total of 479 patients who underwent thyroid lobectomy from January 2008 to July 2014 were retrospectively reviewed. Patients without appropriate Bethesda categorization were excluded. A total of 135 patients (65 FL, 45 BC3, 25 BC4) comprised the study groups. The sensitivity and specificity of FS within these three categories were determined. RESULTS: In the FL group, 6 of 65 patients were found to have thyroid cancer. Three were identified on frozen section (FS) resulting in a sensitivity and specificity of 50% and 100%, respectively. Thus, FS changed the operation in 3 of 65 cases (4.6%). In the BC3 group, 5 of 45 patients were found to have cancer. One was identified on FS resulting in a sensitivity and specificity of 20% and 100%, respectively. Thus, FS changed the operation in 1 of 45 patients (2.2%). In the BC4 group, 4 of 25 patients were found to have cancer. Two were identified on FS resulting in a sensitivity and specificity of 50% and 100% respectively. Thus, FS changed the operation in 2 of 25 patients (8%). CONCLUSIONS: There is improved utility of FS in BC 4 patients as 8% avoided reoperation. However, this benefit hinges on surgeon practice regarding the management of differentiated thyroid cancer >1 cm and <4 cm. PMID- 27664889 TI - Preoperative cancer cachexia and short-term outcomes following surgery. AB - BACKGROUND: Cancer cachexia is an important measure of physiologic reserve associated with worse survival and represents an actionable factor for the cancer population. However, the incidence of cachexia in surgical cancer patients and its impact on postoperative outcomes are currently unknown. METHODS: A prospective cohort study enrolling patients having elective cancer surgery (2012 2014) at a Veterans Affairs tertiary referral center. Preoperative cancer cachexia (weight loss >=5% over 6-mo period before surgery) was the predictor of interest. The primary outcome was 60-d postoperative complications (VA Surgical Quality Improvement Program). Patients were grouped by body mass index (BMI) category (<25, 25-29.9, >=30), and interaction between cachexia and BMI was tested for the primary outcome. Multivariate logistic regression was used to examine the association between preoperative cachexia and postoperative complications. RESULTS: Of 253 patients, 16.6% had preoperative cachexia, and 51.8% developed >= 1 postoperative complications. Complications were more common in cachectic patients (64.3% versus 49.3%, P = 0.07). This association varied by BMI category, and interaction analysis was significant for those with normal or underweight BMI (BMI < 25, P = 0.03). After multivariate modeling, in patients with normal or underweight BMI, preoperative cachexia was associated with higher odds of postoperative complications (odds ratios, 5.08 [95% confidence intervals, 1.18-21.88]; P = 0.029). Additional predictors of complications included major surgery (3.19 [1.24-8.21], P = 0.01), ostomy (4.43 [1.68-11.72], P = 0.003), and poor baseline performance status (2.31 [1.05-5.08], P = 0.03). CONCLUSIONS: Cancer cachexia is common in surgical patients, and is an important predictor of postoperative complications, though its effect varies by BMI. As a modifiable predictor of worse outcomes, future studies should examine the role of cachexia treatment before cancer surgery. PMID- 27664890 TI - Recovery and convalescence after laparoscopic surgery for appendicitis: A longitudinal cohort study. AB - BACKGROUND: Information about predictors for the duration of convalescence and the overall general wellbeing after laparoscopic surgery for suspected appendicitis is missing in the scientific literature. We aimed to describe and identify predictors for the duration of convalescence and the quality of recovery for patients undergoing laparoscopic surgery for suspected appendicitis. METHODS: A prospective cohort of adult patients undergoing laparoscopic surgery for suspected appendicitis was performed between July 2014 and December 2014. Patients completed a QoR-15 questionnaire six times during the 30-d postoperative period. Time until resumption of recreational and occupational activities was recorded. Potential predictors for the duration of convalescence and the quality of recovery measured by the QoR-15 score were identified. RESULTS: A total of 108 patients were included, and 95 patients were eligible for analysis. The median duration of convalescence was 13 d. Disease, depressive mood, level of recreational activities, age, and pain at rest on the first postoperative day were significant predictors of the duration of convalescence. Gender, postoperative complications, disease, and anxiety were significant predictors of the quality of recovery during the 30-d postoperative period. A 10% increase in the QoR-15 score increased the hazard ratio of 1.24 (95% confidence interval, 1.08-1.43, P = 0.002) for ending the period of convalescence. CONCLUSIONS: Duration of convalescence after laparoscopic surgery for appendicitis seems long. Psychological factors, demographical factors, and perioperative outcomes were important predictors for the quality of recovery and the duration of convalescence. Increased quality of recovery is associated with a shorter period of convalescence. PMID- 27664891 TI - Long-term central venous access in a pediatric leukemia population. AB - BACKGROUND: Central venous access devices (CVADs) play an important role in the management of pediatric oncology patients; unfortunately, they are also associated with potentially serious complication rates. We hypothesized that, despite the significantly different disease courses typical of acute lymphoblastic leukemia and acute myelogenous leukemia, there would be identifiable risk factors for premature CVAD removal. METHODS: We retrospectively studied clinical characteristics and procedure records for all patients admitted with a leukemia diagnosis at our institution from May 2009 to July 2014. RESULTS: Our observed perioperative complication rate was 6%; over 70% of lines had at least one long-term complication (thrombosis, catheter-related bloodstream infection, or unexplained line malfunction). Obesity (odds ratio [OR], 6.9; 95% CI, 1.62-29.43), preoperative dosage of packed red blood cells (in mL/kg; OR, 3.13; 1.07-9.21), bloodstream infection (OR, 5.75; 1.69-19.56) were associated with increased risk of premature catheter removal; unexplained malfunction was associated with a lower risk (OR, 0.28; 0.09-0.93). CONCLUSIONS: Obesity, the preoperative dosage of packed red blood cells, the presence of a bloodstream infection, and unexplained line malfunction are significant predictors of premature CVAD removal in a pediatric leukemia population. PMID- 27664892 TI - Effects of hydrogen sulfide on cognitive dysfunction and NR2B in rats. AB - BACKGROUND: Hepatic ischemia/reperfusion (hepatic I/R) has been found to induce cognitive dysfunction. The NR2B subunit of N-methyl-D-aspartate (NMDA) receptors is a major factor in memory and learning processes, and hydrogen sulfide (H2S) may modulate this NMDA receptor. Therefore, in this study, sodium hydrosulfide (NaHS, a donor of H2S) was administered in an animal model of hepatic I/R to investigate the effects of H2S on cognitive impairment and expression of NR2B. MATERIALS AND METHODS: NaHS (5 mg/kg) or normal saline was administered intraperitoneally once a day for 11 consecutive days, during which a rat model of 70% hepatic I/R was established on the fourth day. Cognitive function was evaluated using a Morris water maze, mRNA and protein levels of the NR2B subunit were detected in the hippocampus by RT-PCR and Western blotting. All these tests were performed on postoperative days 1, 3, 5, and 7. RESULTS: Cognitive dysfunction was detected in the hepatic I/R group, and this dysfunction was associated with a decrease in the mRNA and protein levels of the NR2B subunit of the NMDA receptors in the hippocampus. In contrast, treatment with NaHS significantly ameliorated the impairment of cognitive function caused by hepatic I/R, and an increase in mRNA and protein levels of the NR2B subunit was detected in the corresponding hippocampus tissues. CONCLUSIONS: The present data suggest that H2S exerts a protective effect on hepatic I/R-induced cognitive impairment, and this effect may be associated with the NR2B subunit of the NMDA receptors. H2S may represent a novel therapeutic agent for the treatment of postoperative cognitive dysfunction after liver surgery. PMID- 27664893 TI - Strength and histology of a nanofiber scaffold in rats. AB - BACKGROUND: Full-thickness soft tissue defects from congenital absence or traumatic loss are difficult to surgically manage. Healing requires cell migration, organization of an extracellular matrix, inflammation, and wound coverage. PLCL (70:30 lactide:caprolactone, Purac), poly(propylene glycol) nanofibrous scaffolds enhance cell infiltration in vitro. This study compares strength and tissue ingrowth of aligned and unaligned nanofibrous scaffolds to absorbable and permanent meshes. We hypothesize that PLCL nanofibrous grafts will provide strength necessary for physiological function while serving as a scaffold to guide native tissue regeneration in vivo. MATERIALS AND METHODS: Abdominal wall defects were created in 126 rats followed by underlay implantation of Vicryl, Gore-Tex, aligned, or unaligned PLCL Nanofiber mesh. Specimens were harvested at 2, 6, and 12 wk for strength testing and 2, 12, and 24 wk for histopathologic evaluation. Specimens were graded for cellular infiltration, multinucleated giant cells (MNG), vascularity, and tissue organization. Mean scores were compared and analyzed with non-parametric testing. RESULTS: The PLCL grafts maintained structural integrity until at least 12 wk and exhibited substantial tissue replacement at 24 wk. At 12 wk, only the aligned PLCL had persistent cellular infiltration of the graft, whereas both aligned and unaligned PLCL grafts showed the presence of MNG. The presence of MNGs decreased in the aligned PLCL graft by 24 wk. CONCLUSIONS: The aligned PLCL nanofiber mesh offers early strength comparable to Gore-Tex but breaks down and is replaced with cellular ingrowth creating a favorable option in management of complex surgical wounds or native soft tissue defects. PMID- 27664894 TI - Periadventitial adipose tissue modulates the effect of PROLI/NO on neointimal hyperplasia. AB - BACKGROUND: Periadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia; however, the effect of periadventitial adipose tissue on the efficacy of NO at inhibiting neointimal hyperplasia has not been studied. The aim of our study was to assess the effect of NO in the presence and absence of periadventitial adipose tissue. We hypothesized that removal of periadventitial adipose tissue will increase neointimal formation and that NO will be more effective at inhibiting neointimal hyperplasia. METHODS: The effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by (3)H-thymidine incorporation in adipocyte conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague-Dawley rats. Before balloon injury, periadventitial adipose tissue was removed (excised model) or remained intact (intact model). Treatment groups included injury or injury with periadventitial application of PROLI/NO. Adiponectin receptor (AR) levels were assessed via immunofluorescence. RESULTS: Adipocyte-conditioned media had an antiproliferative effect on 3T3 and AF and a proproliferative effect on VSMC in vitro. Interestingly, NO was less effective at inhibiting 3T3 and AF proliferation and more effective at inhibiting VSMC proliferation in adipocyte-conditioned media. In vivo, the excised group showed increased neointimal hyperplasia 2 wk after surgery compared with the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared with the intact group. Although NO inhibited or had no impact on AR levels in the intact group, NO increased AR levels in media and adventitia of the excised group. CONCLUSIONS: These data show that periadventitial adipose tissue plays a role in regulating the arterial injury response and the efficacy of NO treatment in the vasculature. PMID- 27664895 TI - A comparison of initial lactate and initial base deficit as predictors of mortality after severe blunt trauma. AB - BACKGROUND: After injury, base deficit (BD) and lactate are common measures of shock. Lactate directly measures anaerobic byproducts, whereas BD is calculated and multifactorial. Although recent studies suggest superiority for lactate in predicting mortality, most were small or analyzed populations with heterogeneous injury severity. Our objective was to compare initial BD with lactate as predictors of inhospital mortality in a large cohort of blunt trauma patients all presenting with hemorrhagic shock. MATERIALS AND METHODS: The Glue Grant multicenter prospective cohort database was queried; demographic, injury, and physiologic parameters were compiled. Survivors, early deaths (<=24 h), and late deaths were compared. Profound shock (lactate >= 4 mmol/L) and severe traumatic brain injury subgroups were identified a priori. Chi-square, t-test, and analysis of variance were used as appropriate for analysis. Multivariable logistic regression and area under the receiver operating characteristic curve analysis assessed survival predictors. P < 0.05 was significant. RESULTS: A total of 1829 patients met inclusion; 289 (15.8%) died. Both BD and lactate were higher for nonsurvivors (P < 0.00001). After multivariable regression, both lactate (odds ratio [OR] 1.17; 95% confidence interval [CI]: 1.12-1.23; P < 0.00001) and BD (OR 1.04; 95% CI: 1.01-1.07; P < 0.005) predicted overall mortality. However, when excluding early deaths (n = 77), only lactate (OR 1.12 95% CI: 1.06-1.19; P < 0.0001) remained predictive but not BD (OR 1.00 95% CI: 0.97-1.04; P = 0.89). For the shock subgroup, (n = 915), results were similar with lactate, but not BD, predicting both early and late deaths. Findings also appear independent of traumatic brain injury severity. CONCLUSIONS: After severe blunt trauma, initial lactate better predicts inhospital mortality than initial BD. Initial BD does not predict mortality for patients who survive >24 h. PMID- 27664896 TI - Intensive care unit admission predicts hospital readmission in pediatric trauma. AB - BACKGROUND: Hospital readmission in adult trauma is associated with significant morbidity, mortality, and resource utilization. In this study, we examine pediatric intensive care unit (PICU) admission as a risk factor for hospital readmission in pediatric trauma. MATERIALS AND METHODS: This was a retrospective cohort study of patients aged 1 through 19 y in the Pediatric Health Information System database discharged with a trauma diagnosis. Patient and clinical variables included demographics, payer status, length of stay, chronic comorbid conditions, presence of mechanical ventilation, all-patient refined diagnosis related group and calculated severity of illness, and discharge disposition. The main outcome variable was hospital readmission within 30 d of discharge. Odds ratios (ORs) were calculated in both univariate and multivariate analyses with corresponding 95% confidence intervals (CIs). RESULTS: During the 5-year study period, 90,467 patients were admitted with a trauma diagnosis, of which 16,279 (18.0%) were admitted to the PICU. Hospital readmissions occurred in 3.1% of patients. On univariate analysis, patients admitted to the PICU on the first day of hospital admission (direct PICU admission), and those first admitted to the PICU after the day of hospital admission (delayed PICU admission), had 2-3 times the risk of hospital readmission compared with those never admitted to the PICU (4.8% versus 7.2% versus 2.7%, respectively, P < 0.001). On multivariate analysis, controlling for demographic and clinical variables, the adjusted ORs for hospital readmission in patients with direct and delayed PICU admission were 1.34 (95% CI 1.20-1.50) and 1.88 (95% CI 1.50-2.35) versus no PICU admission, respectively. CONCLUSIONS: PICU admission, either direct or delayed, during hospitalization for trauma care is an independent risk factor for hospital readmission within 30 d of discharge. Further risk stratification may help focus resources on high-risk patients to improve clinical outcomes and reduce readmissions. PMID- 27664897 TI - Erythropoietin-activated mesenchymal stem cells promote healing ulcers by improving microenvironment. AB - BACKGROUND: Mesenchymal stem cell (MSC) transplantation is an effective treatment therapy for ischemic ulcers. However, in high-glucose microenvironment, the original inflammation-inhibiting function of MSCs leads to turns into secreting large amounts of inflammatory mediators, such as tumor necrosis factor alpha, for example, which decreases their capacity and becomes poor quality stem cells over inflammation cells for diabetic foot ulcers repair in the healing of diabetic foot ulcers. Erythropoietin (EPO) is an anti-inflammatory, proangiogenic cytokine. It is unclear whether EPO-activated MSCs with biomaterials can promote the effective healing of diabetic foot ulcers. METHODS: Cultivated MSCs in MSC-L, MSC-H, EPO-G, Akt-G, and mTOR-G, then separated the supernatant-conditioned medium of these groups to stimulate human umbilical vein endothelial cells on proliferation and migration experiments; a new type of biomaterial planted with the EPO-activated MSCs was applied to the diabetic foot ulcers of the C57 mice. RESULTS: In vitro experiments showed that EPO could stimulate MSCs to secrete vascular endothelial growth factor in high-glucose microenvironment. More importantly, EPO could reduce the damage to MSCs by high-glucose microenvironment, promote their proliferation and migration functions, and inhibit the high-glucose-induced MSCs from secreting the inflammatory mediator tumor necrosis factor alpha. In vivo experiments showed greater angiogenesis in EPO-MSC group than in control group, ulcer healing in EPO-MSC group was significantly better than that in control group, and MSCs partially differentiated into endothelial cells. EPO-activated MSCs could inhibit the monocyte invasion of localized diabetic foot ulcers. CONCLUSIONS: Our results indicate that EPO-activated MSCs can promote the effective healing of diabetic foot ulcers. The mechanism is that EPO can change stem cells from excessive inflammation into general inflammation and improved diabetic foot ulcers inflammatory microenvironment. PMID- 27664898 TI - Comparison between metallic stent and transanal decompression tube for malignant large-bowel obstruction. AB - BACKGROUND: The short-term safety and efficacy of a self-expandable metallic colonic stent (SEMS) insertion followed by elective surgery, "bridge to surgery (BTS)", for malignant large-bowel obstruction (MLBO) have been well described comparing with emergency surgery. The aim of this study was to compare short-term outcomes of endoscopic decompression using a SEMS versus a transanal decompression tube (TDT). MATERIALS AND METHODS: From January 2005 to November 2014, a total of 101 patients with MLBO underwent surgery at our single institution were retrospectively identified. Among them, 73 patients who underwent preoperative complete insertion of a decompression device (TDT, n = 45; SEMS, n = 28) were finally included in this study. Six patients with incomplete insertion of a decompression device (TDT, n = 5; SEMS, n = 1) were also excluded. The primary endpoints of this study were the postoperative morbidity and mortality rates. The secondary endpoints were decompression-related outcomes. Additionally, propensity score matched (PSM) analysis was conducted in short-term outcomes between the groups. RESULTS: The SEMS group had significantly higher proportion of right-sided tumor and bigger tumor size compared with those of the TDT group. The SEMS group had a significantly higher proportion of patients who underwent laparoscopic surgery, and consequently, a longer surgical duration than did the TDT group. Higher rates of insertion failure and perforation were recognized in the TDT group than in the SEMS group (10.0% versus 3.6% and 8.9% versus 0.0%, respectively), although these differences were not statistically significant (P = 0.406 and 0.291, respectively). The two groups showed similar occurrences of anastomotic leakage, bowel obstruction, overall complications, and mortality. Compared with the TDT group, the SEMS group had a significantly lower rate of surgical site infection (24.4% versus 3.6%, respectively; P = 0.023 and P = 0.025 after PSM) and a shorter length of hospital stay (median, 21 d [interquartile range, 18-29 d] versus 38 d [interquartile range, 28-45 d], respectively; P = 0.015 and P = 0.003 after PSM). Solid food intake after decompression and preoperative temporary discharge occurred only in the SEMS group. CONCLUSIONS: Preoperative SEMS insertion for MLBO is effective with at least equivalent short-term outcomes and superior preoperative quality of life compared with decompression using TDT. PMID- 27664899 TI - Multidisciplinary approach to decrease pediatric trauma undertriage. AB - BACKGROUND: Trauma activation and/or leveling criteria are designed to balance the potential harm to individual patients from undertriage (UT) of severe injuries versus overutilization of resources from overtriage (OT) of lesser injuries. The American College of Surgeons (ACS) recommends an acceptable UT rate <=5% and OT 25%-50%. To improve UT or OT, an intervention was performed to (1) improve accuracy in following established leveling criteria and (2) modify activation criteria in an evidence-based manner to better identify severely injured children. METHODS: Results from a prospective, interventional process improvement study performed at an ACS-verified level I pediatric trauma center are reported. The baseline period included all pediatric trauma patients who met registry inclusion criteria for 2010. The intervention period included two consecutive 3-mo periods in 2011-2012; phase I of the study involved moving the leveling responsibility from emergency department physicians to the nursing care team leaders. Phase II of the study implemented revised leveling criteria. Sustainability was assessed by evaluating data from 2014. RESULTS: In phase I, accuracy in assigned trauma activation level improved from 70% to 99%. UT decreased 10%-8%, and OT decreased 37.5%-33.3%. In phase II, UT decreased 8% 5.1%, and OT increased 33%-40%. Adherence to the activation criteria remained stable (95%). For 2014, UT was 5.3% and OT was 18.2% demonstrating sustainability. CONCLUSIONS: Shifting trauma leveling responsibilities to nursing care team leaders improved accuracy. Revising the activation criteria to include Center for Disease Control and ACS guidelines, as well as tailoring the activation criteria to the program-specific population, further reduced UT rates in a sustainable fashion. PMID- 27664900 TI - The role of computed tomography angiography in the detection of aerodigestive tract injury following penetrating neck injury. AB - BACKGROUND: The purpose of this study was to audit our experience with computed tomography angiography (CTA) for the detection of aerodigestive tract injury (ADTI) following penetrating neck injury (PNI) and to assess the significance of deep surgical emphysema on CTA. METHODS: A prospectively maintained trauma registry at the Pietermaritzburg Metropolitan Trauma Service, Pietermaritzburg, South Africa was retrospectively interrogated. The data of all patients with PNI investigated with CTA over a 4-y period were reviewed. All findings of deep surgical emphysema were correlated to an aggregate standard of reference for ADTI as demonstrated by results from clinical examination, surgical neck exploration, endoscopy or contrasted swallow to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this finding. RESULTS: A total of 383 patients underwent a CTA for PNI. A total of 94 vascular injuries were identified on 78 positive CTA studies. The sensitivity and specificity of CTA in detecting a vascular injury were 94.4% and 96.7%. Of the 383 patients investigated a total of 38 patients were diagnosed with digestive tract injury (DTI), and all of these patients were found to have deep surgical emphysema on CTA, except for one patient with a clinically insignificant oral cavity injury. Another 126 patients also had deep surgical emphysema on CTA but no DTI. The sensitivity, specificity, PPV, and NPV of deep surgical emphysema for the diagnosis of confirmed DTI in PNI were therefore 97.4%, 63.5%, 22.7%, and 99.5%, respectively. The sensitivity and NPV were, however, 100% when clinically insignificant injuries were excluded. Including patients with confirmed airway injuries and excluding all patients with pneumothoraces yielded a sensitivity, specificity, PPV, and NPV of 94.1%, 71.9%, 30.0%, and 98.9%, respectively, for the identification of ADTI. When excluding surgically irrelevant injuries, the sensitivity and NPV were again both 100%. CONCLUSIONS: CTA for PNI has a high sensitivity and specificity for demonstrating vascular injury. The absence of deep surgical emphysema in the deep cervical fascial planes virtually excludes surgically significant ADTI. The presence of deep surgical emphysema is nonspecific but warrants further investigation. PMID- 27664901 TI - Leukocyte filtration and postoperative infections. AB - BACKGROUND: Leukocyte filtration has been hypothesized to reduce the risk of postoperative infections by alleviating the immunosuppressive effect of whole blood. However, the literature regarding the clinical efficacy of leukocyte filtration remains conflicted. This meta-analysis investigates the impact of allogeneic and autologous leukocyte-filtered blood transfusions on the incidence of postoperative infections in adult surgical patients. METHODS: A comprehensive literature search of PubMed, Google Scholar, and Cochrane Central Registry of Controlled trials (1966-2016) was completed for all published randomized controlled trials. Postoperative infections under "as-per-protocol" (APP) and "intention-to-treat" (ITT), length of stay, and mortality were analyzed. RESULTS: Sixteen randomized controlled trials involving 6586 randomized (ITT) patients (4615 APP patients) in various clinical settings were evaluated. The leukocyte filtered blood group demonstrated an overall 26% risk reduction in postoperative infections when analyzed by APP (relative risk [RR] = 0.74; 95% confidence interval [CI, 0.60-0.92]; P = 0.007) and a 22% risk reduction when analyzed by ITT (RR = 0.78; 95% CI [0.65-0.94]; P = 0.009). Leukocyte-filtered blood was also associated with a significant reduction in length of stay (standardized difference of mean [SDM] = -0.74; 95% CI [-1.32 to -0.15]; P = 0.014) and all cause mortality (RR = 0.74; 95% CI [0.57-0.95]; P = 0.018). CONCLUSIONS: Leukocyte-filtered blood transfusions are associated with significantly lower postoperative infection rates in both the APP and ITT populations. Leukocyte filtration also shortens length of stay and decreases all-cause mortality in surgical patients and should be considered in all surgical patients. PMID- 27664902 TI - Host sphingosine kinase 1 worsens pancreatic cancer peritoneal carcinomatosis. AB - BACKGROUND: There are no effective treatments for pancreatic cancer peritoneal carcinomatosis (PC) or cancer dissemination in abdominal cavity. Sphingosine-1 phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays critical roles in cancer progression. We reported that SphK1, but not SphK2, is responsible for S1P export from breast cancer cells and recently discovered that S1P is linked to inflammation and cancer in colitis associated cancer progression. Given the fact that inflammation is known to be essential for the establishment and progression of PC, we hypothesized that SphK1 in the host animals is involved in progression of pancreatic cancer PC. METHODS: Murine pancreatic adenocarcinoma panc02-luc cells were intraperitoneally injected into wildtype or SphK1 knockout (KO) mice to generate a syngeneic PC model. Cell proliferation and apoptosis were determined by Ki67 and TUNEL staining, respectively. RESULTS: All the animals developed panc02-luc PC. SphK1 KO mice developed significantly less tumor burden, less total tumor weight, and fewer number of PC nodules at 14 d after implantation. Histologically, less inflammatory cell infiltration and less cancer cell proliferation were observed in the tumors. There was no difference in apoptosis. CONCLUSIONS: Our results raise an intriguing possibility that S1P generated by SphK1 in the host promotes pancreatic cancer PC progression by stimulation of proliferation of cancer cells. PMID- 27664903 TI - VNTR diversity in Yersinia pestis isolates from an animal challenge study reveals the potential for in vitro mutations during laboratory cultivation. AB - Underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. Although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. Here, we investigated tissue samples and Yersinia pestis isolates from a rodent laboratory challenge with strain CO92 using whole genome sequencing and multi-locus variable number tandem repeat (VNTR) analysis (MLVA). We identified six VNTR mutations that were found to have occurred in vitro during laboratory cultivation rather than in vivo during the rodent challenge. In contrast, no single nucleotide polymorphism (SNP) mutations were observed, either in vivo or in vitro. These results were consistent with previously published mutation rates and the calculated number of Y. pestis generations that occurred during the in vitro versus the in vivo portions of the experiment. When genotyping disease outbreaks, the potential for in vitro mutations should be considered, particularly when highly variable genetic markers such as VNTRs are used. PMID- 27664904 TI - Optical monitoring of retinal respiration in real time: 670 nm light increases the redox state of mitochondria. AB - Mitochondria play a key role in ageing and disease. Their membrane potentials and ATP production decline with age and this is associated with progressive inflammation, cell loss and death. Here we use broadband Near-Infrared Spectroscopy (NIRS) to non-invasively measure in-vivo changes in aged retinal mitochondrial respiration following exposure to 670 nm, which improves mitochondrial performance and reduces inflammation. Low power NIR light was shone into the eye via a fibre optic and the reflection monitored to measure signature changes in the oxidation of cytochrome c oxidase (COX) in complex IV of the electron transport chain. Changes in retinal haemodynamics and oxygenation were also recorded simultaneously with COX by measuring changes in oxygenated and deoxygenated haemoglobin (Delta[HbO2] and Delta[HHb]). Retinae of aged rats exposed to 670 nm for 5 mins showed consistent progressive increases in oxidation of COX 5 mins post exposure. This remained significantly greater than baseline for up to 2 h. This was not seen when retinae were exposed to 420 nm light of the same power or when no light was applied. 670 nm exposure significantly increased total haemoglobin concentration (Delta[HbT] = Delta[HbO2] +Delta[HHb]) but not haemoglobin difference (Delta[HbDiff] = Delta[HbO2] -Delta[HHb]). There were no changes in blood metrics in association with 420 nm light or when no light exposure was given. Hence, brief 670 nm exposure that is associated with reduced inflammation has a significant positive impact on the redox state of COX in aged retinae. The relative redox state of retinal COX may provide a valuable biomarker in ageing and macular degeneration where declining mitochondrial function is implicated. PMID- 27664905 TI - Axonal protection by thioredoxin-1 with inhibition of interleukin-1beta in TNF induced optic nerve degeneration. AB - Interleukin (IL)-1beta, a proinflammatory cytokine, is a key mediator in several acute and chronic neurological diseases. Thioredoxin-1 (TRX1) acts as an antioxidant and plays a protective role in certain neurons. We examined whether exogenous TRX1 exerts axonal protection and affects IL-1beta levels in tumor necrosis factor (TNF)-induced optic nerve degeneration in rats. Immunoblot analysis showed that IL-1beta was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with recombinant human (rh) TRX1 exerted substantial protective effects against TNF-induced axonal loss. The increase in the IL-1beta level in the optic nerve was abolished by rhTRX1. Treatment with rhTRX1 also significantly inhibited increased glial fibrillary acidic protein (GFAP) levels induced by TNF. Immunohistochemical analysis showed substantial colocalization of IL-1beta and GFAP in the optic nerve after TNF injection. These results suggest that IL-1beta is upregulated in astrocytes in the optic nerve after TNF injection and that exogenous rhTRX1 exerts axonal protection with an inhibitory effect on IL-1beta. PMID- 27664906 TI - Dr. Hugh Hampton Young's Impact on Venereal Disease During World War I: The Chaste of American Soldiers. PMID- 27664907 TI - In search of best practice for postpartum depression screening: is once enough? AB - BACKGROUND: Postpartum depression (PPD) causes significant morbidity in postpartum women and their newborns. Universal screening is mandated in many states despite little information on optimal interval and frequency of screening. OBJECTIVE: The objective of this study was to determine whether the early Edinburgh Postnatal Depression Scale (EPDS) score (done within 96h after delivery) is predictive of the late EPDS score (done at outpatient postpartum visit). STUDY DESIGN: This retrospective cohort study selected 256 women delivered at Cooper University Hospital in Camden, NJ in 2013. All patients who presented to the office during the postpartum period completed the EPDS questionnaire, in accordance to our usual practice. The delivery and outpatient records were reviewed for demographic data, EPDS scores and outcomes. Three groups of EPDS scoring were analyzed: <10 (low risk for PPD), 10-13 (borderline risk for PPD), and >=14 (high risk for PPD). Early and late EPDS scores were compared using Pearson Chi Square test. The relationship between scores was calculated using the Spearman Rho Correlation test. Assuming the EPDS groups would not change, a sample of 200 was needed with 80% power and 5% alpha-error. RESULTS: EPDS scores remained the same or improved in 92.2% (189/205) of women. The 16 women whose scores worsened were more likely to have had a diagnosis of prior psychiatric illness (50% vs 16.4%, p=0.003) and/or a diagnosis of fetal anomaly (12.5 vs 1.6%, p=0.05). An early EPDS score of <10 had a 92.7% probability of maintaining low risk screening (EPDS <10) at a later time. CONCLUSIONS: In low risk women, there is good correlation between early and late EPDS scores and so these women may not need to be rescreened. Therefore, we should redirect the limited available resources from screening low risk women multiple times, towards provision of follow-up care for the smaller number of women at highest risk. We propose that "women know your number" (EPDS prior to discharge); and providers re-screen only those women who score positive on PAP10, which stands for Psychiatry history, Anomaly, Preterm delivery, and EPDS score of 10 or more. PMID- 27664909 TI - Iris Recognition Technology (or, Musings While Going through Airport Security). PMID- 27664908 TI - A genetic cluster of patients with variant xeroderma pigmentosum with two different founder mutations. AB - BACKGROUND: Xeroderma pigmentosum (XP) is a rare human syndrome associated with hypersensitivity to sunlight and a high frequency of skin tumours at an early age. We identified a community in the state of Goias (central Brazil), a sunny and tropical region, with a high incidence of XP (17 patients among approximately 1000 inhabitants). OBJECTIVES: To identify gene mutations in the affected community and map the distribution of the affected alleles, correlating the mutations with clinical phenotypes. METHODS: Functional analyses of DNA repair capacity and cell-cycle responses after ultraviolet exposure were investigated in cells from local patients with XP, allowing the identification of the mutated gene, which was then sequenced to locate the mutations. A specific assay was designed for mapping the distribution of these mutations in the community. RESULTS: Skin primary fibroblasts showed normal DNA damage removal but abnormal DNA synthesis after ultraviolet irradiation and deficient expression of the Poleta protein, which is encoded by POLH. We detected two different POLH mutations: one at the splice donor site of intron 6 (c.764 +1 G>A), and the other in exon 8 (c.907 C>T, p.Arg303X). The mutation at intron 6 is novel, whereas the mutation at exon 8 has been previously described in Europe. Thus, these mutations were likely brought to the community long ago, suggesting two founder effects for this rare disease. CONCLUSIONS: This work describes a genetic cluster involving POLH, and, particularly unexpected, with two independent founder mutations, including one that likely originated in Europe. PMID- 27664910 TI - Epicapsular Stars. PMID- 27664911 TI - Pigmented Paravenous Retinochoroidal Atrophy. PMID- 27664912 TI - Merkel Cell Carcinoma of the Eyelid. PMID- 27664913 TI - Antimony Intraocular Foreign Body with an Intact Electroretinogram. PMID- 27664914 TI - Re: Cheng et al.: Amiodarone-associated optic neuropathy: a nationwide study (Ophthalmology 2015;122:2553-9). PMID- 27664915 TI - Reply. PMID- 27664916 TI - Re: Clark et al.: Intravitreal aflibercept for macular edema following branch retinal vein occlusion: 52-week results of the VIBRANT Study (Ophthalmology 2016;123:330-6). PMID- 27664917 TI - Reply. PMID- 27664918 TI - Re: Panarelli et al.: A retrospective comparison of primary Baerveldt implantation versus trabeculectomy with mitomycin C (Ophthalmology 2016;123:789 95). PMID- 27664919 TI - Reply. PMID- 27664920 TI - Re: Lambert SR: Should glasses be prescribed for all children with moderate hyperopia? (Ophthalmology 2016;123:676-8). PMID- 27664921 TI - Polyphenolic-polysaccharide conjugates of Sanguisorba officinalis L. with anticoagulant activity mediated mainly by heparin cofactor II. AB - A macromolecular complex has been isolated from the dried flowering parts of medicinal plant Sanguisorba officinalis L. (So) by multi-step extraction procedure, including that with extraction by organic solvents to degrease the plant material, then with hot alkali, followed by neutralization, partitioning with organic solvents and dialysis. The complex was purified by size-exclusion chromatography into five fractions labeled as So1-So5. Individual fractions differed in the chemical composition and molecular weight distribution patterns. In vitro anticoagulant activity tests showed in all fractions more or less important inhibition of plasma clots, however, So3 and So4 were the most active. The anticoagulant activity of So3 was even more significant than that of the unfractionated complex So. These S. officinalis conjugates were able to inhibit mainly the activity of thrombin when they were mediated by heparin cofactor II, but what was unexpected they were the non-direct inhibitors of factor Xa, mediated by antitrombin, where such mechanism of action is typical for a highly sulphated glycosaminoglycans. PMID- 27664922 TI - Purification of polyphenol oxidase from borage (Trachystemon orientalis L.) by using three-phase partitioning and investigation of kinetic properties. AB - In this study a Polyphenol oxidase from borage plant was purified with 3.59-fold enrichment in the specific activity and 68.75% recovery of the total activity by using three-phase partitioning purification technique for the first time. Its molecular weight was found around 80kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis. The optimum pH and temperature values of the enzyme for the used four substrates ranged between the pH 5.0-7.5 and 5-30 degrees C. The kcat/Km values showed that the enzyme has the greatest reactivity toward caffeic acid among the substrates used. Ascorbic acid, l-cysteine and sodium metabisulfite markedly inhibited borage polyphenol oxidase activity. PMID- 27664923 TI - Lipid functionalized biopolymers: A review. AB - Lipids are the main source of energy and widely used for various applications. In this review, the modification of lipids by using them in combination with other biomaterials like natural and synthetic polymers is elaborated. These new blends have characteristic features of both polymers and are characterized by different techniques (NMR, DSC, TGA, IR and Raman spectroscopy etc.) to understand their structure, properties and functional behavior. Lipids are hydrophobic, have anti oxidant and anti-bacterial properties and thus impart hydrophobicity and flexibility to the polymers. While the polymers, on the other hand, make the lipids tougher. Properties of few polymers such as starch, polyethylene protein and chitosan that have brittleness, low combustion rate and hydrophobicity, are improved by incorporation of lipids ultimately increased their flexibility, combustion rate and hydrophobicity respectively. This review article is also focused on emerging fields for the applications of these composite materials. The most notable application of composite materials are in the field of paint industry. PMID- 27664924 TI - Fabrication and characterization of carboxylated starch-chitosan bioactive scaffold for bone regeneration. AB - This study offers new bioactive composite scaffolds from carboxylated starch chitosan for bone regeneration. In order to introduce COOH groups into the scaffolds, chitosan was first dissolved in citric acid and then mixed with different amounts of starch. Various characterization techniques were used to analyze the structure, morphology, compressive strength, and apatite mineralization of the composites, which were compared to pure chitosan scaffolds. The results indicated that chitosan scaffolds showed the highest pore size and porosity, while no apatite deposition was observed even after 14days of soaking in simulated body fluid. For composite samples, the pore size and porosity decreased as the starch content increased. In spite of such decrease, the pore size measurements were in the optimal range for bone regeneration. The bone-like apatite mineralization, compressive strength, carboxyl content, and swelling ratio of the composites increased with additional starch. Cell culture experiments demonstrated that higher starch content can enhance proliferation, ALP activity, and mineralization of osteoblast-like cells (MG63). PMID- 27664925 TI - Swelling behavior of cross-linked dextran hydrogels and preliminary Gliclazide release behavior. AB - In this study, dextran (Dex) has been cross-linked with epichlorohydrin (Ech) to yield cross-linked hydrogels. These gels were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, Thermogravimetric analysis (TGA), and Scanning electron microscopy (SEM). The water absorption behavior of gels was studied in simulating gastric fluid (SGF) and simulating intestinal fluid (SIF) at 37 degrees C. The data was interpreted by various kinetic models. The swelling was found to be totally diffusion controlled. The equilibrium data was also used to calculate network parameters. The antidiabetic drug Gliclazide (Glz) was loaded to the gels and its release was investigated in the media of varying pH, to mimic transition from mouth to colon. Finally, the in vivo study on "Albino Wistar rats" was carried out to investigate the efficiency of the formulations. The drug-loaded hydrogel was found to be quite effective in reducing the glucose level at lower administration frequency as compared to the plain drug. PMID- 27664926 TI - Is there correlation between Abeta-heme peroxidase activity and the peptide aggregation state? A literature review combined with hypothesis. AB - Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by aggregation of amyloid-beta (Abeta) peptide, formation of neurofibrillary tangles, synaptic loss and neuronal cell death, and is manifested clinically by progressive cognitive dysfunction and memory loss. Disease pathogenesis is mainly linked to the formation of Abeta insoluble or soluble oligomeric assemblies. Binding of heme to Abeta has been suggested as the origin of the heme deficiency, peroxidase activity, as well as some oxidative stress mediated AD pathologies, and then differential affinity of heme for human and rodent Abeta peptide has been proposed to account for the susceptibility of humans to AD. This review highlights whether there is any dependency of peroxidase activity of heme-bound Abeta on the Abeta aggregation state or not, with focusing on emerging role of heme in neurodegeneration. Here, several lines of evidence supporting existing contradictory conjectures are discussed. PMID- 27664927 TI - Application of chitosan and chitosan nanoparticles for the control of Fusarium head blight of wheat (Fusarium graminearum) in vitro and greenhouse. AB - Fusarium head blight (FHB) disease caused by Fusarium graminearum is one of the most important diseases of wheat in humid and warm areas. This disease significantly reduces yield as well as seed quality. The aim of this work was to evaluate the possibility of control of FHB by chitosan (CS) and chitosan nanoparticles (CS/NPs). In vitro, the application of various concentrations of CS and CS/NPs showed significant inhibition of both radial mycelial growth and number of colonies formed against F. graminearum. The application of 1000 and 5000ppm concentration of CS and CS/NPs produced maximum inhibition of radial mycelial growth in comparison to the control, respectively. The microscopic examination, of treated F. graminearum with the CS and CS/NPs, showed dehydration and deformation in mycelial growth and some hyphae were collapsed. The maximum percentage reduction number of colonies was observed in 5000ppm concentration of both CS and CS/NPs. To test the effect of CS and CS/NPs on spore germination, four concentrations were used for 4 and 24h incubation. The 24h incubation of F. graminearum spores with a 5000ppm solution of CS greatly reduced the number of germinating spores. In greenhouse trials, the disease severity percentage was low when CS and CS/NPs were applied before fungus inoculation on the plants and 1000ppm concentration. The spores of F. graminearum germinated on the anther, hyphae penetrated into anther and colonized the palea, lemma and glume after 24 and 72 hpi, respectively. Wherease, the spikelets treated with CS and CS/NPs were infected slowly. Light microscopy and TEM observations indicated that mycelium penetrated into the cells through stoma and transited to other cells by cell wall or plasmodesmata. Mycelial growth caused conidia into cells but CS and CS/NPs prevented of it's growth. Results showed that CS and CS/NPs could be a useful biological pesticide for controlling FHB. PMID- 27664928 TI - Effect of crosslinker on drug delivery properties of curcumin loaded starch coated iron oxide nanoparticles. AB - Aminated starch coated iron oxide magnetic nanoparticles loaded with curcumin were synthesized via coprecipitation technique. The nanoparticles were crosslinked by using three different crosslinkers: glutaraldehyde, genipin and citric acid and the effect of crosslinking on different properties of the nanoparticles was evaluated. Characterisation of the nanoparticles was done with FTIR (Fourier Transform Infrared spectroscopy) and XRD (X-Ray Diffraction). Magnetic property study using VSM (Vibrating Sample Magnetometer) showed their superparamagnetic nature. Morphology of the nanoparticles was studied by SEM (Scanning Electron Microscopy) and TEM (Transmission Electron Microscopy). Zeta potential values showed that crosslinking imparted stability to the system. Crosslinking also enhanced drug loading and encapsulation efficiency of the system. Swelling and in vitro studies of the nanoparticles showed that the release of drug was dependent on time, crosslinker nature, crosslinker concentration and pH of the medium. The aminated starch coated nanoparticles also showed good mucoadhesive character. The cell viability assessment by MTT study revealed their compatibility with human lymphocytes cells and their considerable cell growth inhibiting properties with MCF7 and HepG2 cells. The nanoparticles showed good internalization in HepG2 cells along with considerable ROS formation. PMID- 27664929 TI - Effects of the components in rice flour on thermal radical generation under microwave irradiation. AB - The relationships between radical generation under microwave irradiation and the components of various types of rice flour were investigated. Electron paramagnetic resonance (EPR) spectroscopy was used to characterize the radicals found in rice flour samples. The EPR spectra revealed that several types of radical (carbon-centered, tyrosyl and semiquinone) were localized in the starch and protein fractions of the rice flour. The signal intensity of the free radicals was observed to increase exponentially with increasing microwave power and residence time. The rice bran samples exhibited the greatest free radical signal intensity, followed by the brown rice samples and the white rice samples. This finding was consistent for both the native and the microwaved samples. The ratio of rice starch to rice protein also played an important role in the generation of radicals. PMID- 27664931 TI - What is the Research Agenda in Ventilator-associated Pneumonia? PMID- 27664930 TI - Higher incidence of Zika in adult women than adult men in Rio de Janeiro suggests a significant contribution of sexual transmission from men to women. AB - OBJECTIVES: The recent emergence of Zika in Brazil and its association with an increased rate of congenital malformations has raised concerns over its impact on the birth rate in the country. Using data on the incidence of Zika in 2015-2016 and dengue in 2013 and 2015-2016 for the city of Rio de Janeiro (population 6.4 million), a massive increase of Zika in women compared to men was documented. METHODS: The age-adjusted incidence was compared between men and women. A negative binomial Poisson generalized linear model was fitted to the Zika incidence data to determine the significance of sexual transmission statistically. RESULTS: Even after correcting for the bias due to the systematic testing of pregnant women for Zika, there were found to be 90% more registered cases per 100000 women than men in the sexually active age group (15-65 years); this was not the case for age groups <15 years and >65 years. Assuming that infected men transmit the disease to women in their semen, but that the converse is not true, some extra incidence in women is to be expected. An alternate hypothesis would be that women visit doctors more often than men. To test this, the incidence of dengue fever was compared in men and women in 2015 and in 2013 (before Zika reached Rio de Janeiro): in both years, women were 30% more likely to be reported with dengue. CONCLUSION: Women in the sexually active age group are far more likely to get Zika than men (+90% increase); sexual transmission is the most probable cause. Women in the 15-65 years age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health. PMID- 27664932 TI - MicroRNA 182 inhibits CD4+CD25+Foxp3+ Treg differentiation in experimental autoimmune encephalomyelitis. AB - MicroRNA 182 has been found to have a distinct contribution in the clonal expansion of activated- and functioning of specialized-helper T cells. In this study we knocked down microRNA 182 in vivo and induced experimental autoimmune encephalomyelitis (EAE) to determine the influences of microRNA 182 in the Treg cells functional specialization through Foxo1 dependent pathway in the peripheral lymphoid organs. Down-regulation of microRNA 182 significantly increased the proportions of Foxp3+ T cells in the peripheral lymph nodes and spleen. In vivo study verified a positive correlation between microRNA 182 levels and symptom severity of EAE, and a negative correlation between microRNA 182 and the transcriptional factor Foxp3. In vitro polarization study also confirmed the contribution of Foxo1 in microRNA 182 mediated down-regulation of Foxp3+ T cells. Together, our results provide evidence that during the development of EAE, microRNA 182 repressed Treg cells differentiation through the Foxo1 dependent pathway. PMID- 27664933 TI - An emerging role for eotaxins in neurodegenerative disease. AB - Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, CCR3. Beyond their role in innate immunity, recent studies have shown that CCL11 and related molecules may directly contribute to degenerative processes in the central nervous system (CNS). CCL11 levels increase in the plasma and cerebrospinal fluid of both mice and humans as part of normal aging. In mice, these increases are associated with declining neurogenesis and impaired cognition and memory. In humans, elevated plasma levels of CCL11 have been observed in Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and secondary progressive multiple sclerosis when compared to age-matched, healthy controls. Since CCL11 is capable of crossing the blood-brain barrier of normal mice, it is plausible that eotaxins generated in the periphery may exert physiological and pathological actions in the CNS. Here, we briefly review known functions of eotaxin family members during innate immunity, and then focus on whether and how these molecules might participate in the progression of neurodegenerative diseases. PMID- 27664934 TI - Impaired Akt phosphorylation in B-cells of patients with common variable immunodeficiency. AB - Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency characterized by recurrent infections. We evaluated whether defective PI3K/Akt/FoxO pathway could influence B-cell fate. Determination of B cell subsets in CVD patients and healthy donors (HDs) were performed using flow cytometry. We evaluated mRNA and protein expression of PI3K, Akt and FoxO using real-time PCR and flow cytometry, respectively. Moreover, phosphorylated Akt (pAkt) expression in B-cells has been measured by flowcytometry. We identified a significant reduction in the percentage of marginal zone like B-cells, memory B cells (total, switched and unswitched) and plasmablasts in patients, as these decreased B-cell subsets had a significant negative correlation with increased apoptosis in patients. Surprisingly, we identified decreased pAkt expression in B cells of patients than HDs. We described for the first time impaired pAkt expression in B-cells of CVID patients that had a significant correlation with antibody response to the vaccine and worse clinical complications. PMID- 27664935 TI - Influenza virus NS1 protein binds cellular DNA to block transcription of antiviral genes. AB - Influenza NS1 protein is an important virulence factor that is capable of binding double-stranded (ds) RNA and inhibiting dsRNA-mediated host innate immune responses. Here we show that NS1 can also bind cellular dsDNA. This interaction prevents loading of transcriptional machinery to the DNA, thereby attenuating IAV mediated expression of antiviral genes. Thus, we identified a previously undescribed strategy, by which RNA virus inhibits cellular transcription to escape antiviral response and secure its replication. PMID- 27664936 TI - Quantitative assessment of gadolinium deposition in dentate nucleus using quantitative susceptibility mapping. AB - PURPOSE: Gadolinium deposition in dentate nucleus (DN) has been reported after serial administration of gadolinium-based contrast agents (GBCAs). Gadolinium complexes have paramagnetic properties; therefore, we evaluated susceptibility changes of gadolinium deposition in DN using quantitative susceptibility mapping (QSM) for patients after serial administration of GBCAs. MATERIALS AND METHODS: In all, 48 patients with brain tumors, who had had serial GBCA administrations (GBCA group), and 48 healthy volunteers without any history of GBCA administrations (non-GBCA group) were enrolled in this study. Susceptibility values in DN on QSM and DN-to-cerebellum signal intensity ratios on unenhanced T1 -weighted images (T1 ratios) on 3T were analyzed. The relationship between the number of times of GBCA administrations and susceptibility values or T1 ratios were evaluated in the GBCA group. RESULTS: Susceptibility values at DN in the GBCA group were 0.107 +/- 0.029 ppm, and significantly higher than those of the non-GBCA group (0.079 +/- 0.025 ppm) (P < 0.0001). T1 ratios in DN of the GBCA group were 1.059 +/- 0.070, and also significantly higher than that of the non GBCA group (0.993 +/- 0.016) (P < 0.0001). Spearman rank correlation coefficients between susceptibility values and the number of times of linear GBCA administration showed a modest significant correlation (rho = 0.45, P = 0.0015). There was good correlation between T1 ratios and the number of times of linear GBCA administration, as reported previously (rho = 0.76, P < 0.0001). CONCLUSION: Susceptibility values on QSM in DN of the GBCA group, after serial administration of GBCAs, were significantly higher than those of the non-GBCA group. Evidence Level: 3 J. MAGN. RESON. IMAGING 2017;45:1352-1358. PMID- 27664937 TI - Comparative proteome analysis of egg yolk plasma proteins during storage. AB - BACKGROUND: Physical changes such as chicken egg white thinning and egg yolk flattening occur during storage, implying a decline in egg quality. To reveal the deteriorative process related to chicken egg internal quality, a comparative proteomic method was used in this study to analyze the alterations in egg yolk plasma proteins at different storage times (0, 20 and 40 days) under an ambient temperature of 22 +/- 2 degrees C. RESULTS: Using two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of flight tandem mass spectrometry, 33 protein spots representing 12 proteins were identified with significant (P < 0.05) alterations in abundance at different storage times. The proteins that showed significant changes in abundance included serum albumin, vitellogenin fragments, IgY chains, ovalbumin, ovoinhibitor, alpha2 -macroglobulin-like protein 1-like, hemopexin, transthyretin, apolipoprotein A-I and beta2 -glycoprotein I precursor. Accelerating degradation for most egg yolk plasma proteins was observed after prolonged storage (from day 20 to day 40). CONCLUSION: It is likely that the increased degradation of protease inhibitors such as ovoinhibitor and alpha2 -macroglobulin-like protein 1 like during prolonged storage lead to an imbalance of protease and antiprotease in egg yolk, which may play a key role in the degradation of egg yolk proteins. These findings will provide an insight into the effects of storage on egg yolk protein changes and give a deeper understanding of the deteriorative process of chicken egg yolk. (c) 2016 Society of Chemical Industry. PMID- 27664938 TI - In vivo and in vitro effects of selected antioxidants on rabbit meat microbiota. AB - The purpose of this study was to investigate the effect of dietary vitamin E or EconomasETM supplementation on the growth of several background/pathogenic bacteria on rabbit carcasses and hamburgers during refrigerated storage. For 51days, 270 New Zealand rabbits received either a basal diet, or experimental diets enriched with 100 or 200mg/kg of vitamin E or EconomasETM. The bacteria studied were Salmonella, Listeria monocytogenes, Pseudomonas, Enterobacteriaceae, Escherichia coli, coagulase-positive staphylococci, plus both mesophilic and psychrotrophic aerobes. The growth of Listeria monocytogenes on contaminated patties was evaluated through a challenge test. The potential protective or antimicrobial effect of vitamin E or EconomasETM on Listeria monocytogenes or Pseudomonas aeruginosa was assessed in vitro. Diet did not influence the concentrations of bacteria found on rabbit carcasses and developing on hamburgers. Vitamin E (in vivo and in vitro) and EconomasETM in vivo had a protective antioxidant role, while EconomasETM in vitro had strong antibacterial activity against Listeria monocytogenes, but not against Pseudomonas aeruginosa. PMID- 27664939 TI - Formation and maturation of the murine meniscus. AB - Meniscal injuries are commonplace, but current surgical repair procedures do not prevent degenerative joint changes that occur after meniscal injury and often lead to osteoarthritis. Successful tissue regeneration in adults often recapitulates events that occur during embryogenesis, suggesting that understanding the regulatory pathways controlling these early processes may provide clues for developing strategies for tissue repair. While the mouse is now widely used to study joint diseases, detailed knowledge of the basic biology of murine meniscus is not readily available. Here, we examine meniscal morphogenesis in mice from embryonic day 13.5 (E13.5) to 6 months of age using histology, in situ hybridization, and immunohistochemistry. We find that the meniscus is a morphologically distinct structure at E16 when it begins to regionalize. At birth, the meniscus has a distinguishable inner, avascular, round chondrocyte cell region, an outer, vascularized, fibroblast cell region, and a surface superficial zone. Maturation begins at 2 weeks of age when the meniscus expresses type I collagen, type II collagen, type X collagen, and MMP-13 in specific patterns. By 4 weeks of age, small areas of ossification are detected in the anterior meniscal horn, a common feature seen in rodents. Maturation appears complete at 8 weeks of age, when the meniscus resembles the adult structure complete with ossifying tissue that contains bone marrow like areas. Our results provide, the first systematic study of mouse meniscal development and will be a valuable tool for analyzing murine models of knee joint formation and disease. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1683-1689, 2017. PMID- 27664941 TI - Bronchiolitis: More Evidence, Fewer Interventions-Shifting Paradigms With Evidence-based Diagnostics. PMID- 27664940 TI - Long-Term Follow-up of a Randomized Controlled Trial Evaluating a Mobile Health Intervention for Self-Management in Lung Transplant Recipients. AB - Mobile health interventions may help transplant recipients follow their complex medical regimens. Pocket Personal Assistant for Tracking Health (Pocket PATH) is one such intervention tailored for lung transplant recipients. A randomized controlled trial showed Pocket PATH's superiority to usual care for promoting the self-management behaviors of adherence, self-monitoring and communication with clinicians during posttransplant year 1. Its long-term impact was unknown. In this study, we examined associations between Pocket PATH exposure during year 1 and longer term clinical outcomes-mortality and bronchiolitis obliterans syndrome (BOS)-among 182 recipients who survived the original trial. Cox regression assessed whether (a) original group assignment and (b) performance of self management behaviors during year 1 predicted time to outcomes. Median follow-up was 5.7 years after transplant (range 4.2-7.2 years). Pocket PATH exposure had no direct effect on outcomes (p-values >0.05). Self-monitoring was associated with reduced mortality risk (hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.22 0.91; p = 0.027), and reporting abnormal health indicators to clinicians was associated with reduced risks of mortality (HR 0.15; 95% CI 0.04-0.65; p = 0.011) and BOS (HR 0.27; 95% CI 0.08-0.86; p = 0.026), regardless of intervention group assignment. Although Pocket PATH did not have a direct impact on long-term outcomes, early improvements in self-management facilitated by Pocket PATH may be associated with long-term clinical benefit. PMID- 27664942 TI - Pre-mRNA splicing repression triggers abiotic stress signaling in plants. AB - Alternative splicing (AS) of precursor RNAs enhances transcriptome plasticity and proteome diversity in response to diverse growth and stress cues. Recent work has shown that AS is pervasive across plant species, with more than 60% of intron containing genes producing different isoforms. Mammalian cell-based assays have discovered various inhibitors of AS. Here, we show that the macrolide pladienolide B (PB) inhibits constitutive splicing and AS in plants. Also, our RNA sequencing (RNA-seq) data revealed that PB mimics abiotic stress signals including salt, drought and abscisic acid (ABA). PB activates the abiotic stress- and ABA-responsive reporters RD29A::LUC and MAPKKK18::uidA in Arabidopsis thaliana and mimics the effects of ABA on stomatal aperture. Genome-wide analysis of AS by RNA-seq revealed that PB perturbs the splicing machinery and leads to a striking increase in intron retention and a reduction in other forms of AS. Interestingly, PB treatment activates the ABA signaling pathway by inhibiting the splicing of clade A PP2C phosphatases while still maintaining to some extent the splicing of ABA-activated SnRK2 kinases. Taken together, our data establish PB as an inhibitor and modulator of splicing and a mimic of abiotic stress signals in plants. Thus, PB reveals the molecular underpinnings of the interplay between stress responses, ABA signaling and post-transcriptional regulation in plants. PMID- 27664943 TI - Detection of poliovirus infection in children with acute gastroenteritis in Chiang Mai, Thailand. AB - Poliovirus (PV) is typically transmitted by the fecal-oral route, which means that the risk of infection and virus distribution could be achieved by exposure to the virus contaminated in food and water. The aim of this study was to determine the occurrence of PV strains by detecting the virus in pediatric patients who admitted to the hospitals with diarrhea in Chiang Mai, Thailand during 2010-2015. By applying a reverse transcription-polymerase chain reaction and nucleotide sequencing analysis of 1,300 stool specimens collected from pediatric patients, PVs were detected at 0.61% (8 out of 1,300 specimens). Among eight PV positive samples, mixed infection with norovirus or human bocavirus was detected in one each out of eight cases. All PV strains detected in this study were characterized further by phylogenetic analysis of 343 bp of the 5' UTR and 315 bp of the partial VP1 sequences. The results revealed that eight PV strains detected in the present study two of each were PV1 and PV2, and four were PV3 serotypes of the Sabin vaccine strains. The data demonstrated the presence of PV1, PV2, and PV3 Sabin vaccine strains in children with acute gastroenteritis in Chiang Mai, Thailand. J. Med. Virol. 89:775-781, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27664945 TI - Neuronal energy consumption: biophysics, efficiency and evolution. AB - Electrical and chemical signaling within and between neurons consumes energy. Recent studies have sought to refine our understanding of the processes that consume energy and their relationship to information processing by coupling experiments with computational models and energy budgets. These studies have produced insights into both how neurons and neural circuits function, and why they evolved to function in the way they do. PMID- 27664944 TI - Microinfarcts in an older population-representative brain donor cohort (MRC CFAS): Prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel Disease. AB - INTRODUCTION: Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship with dementia, mobility and cerebrovascular disease in an older population representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD). METHODS: Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n = 331). Nine brain areas were staged according to the number of areas affected. RESULTS: 36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95% CI 1.02; 1.96, P = 0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95% CI 1.05 1.74; P 0.018) and falls (OR 1.96, 95% CI 1.11-3.43; P = 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions (WMLs), lacunes and significant arteriosclerosis, were assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of WMLs, lacunes and microinfarcts. CONCLUSION: Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on WMLs, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis. PMID- 27664946 TI - Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO). AB - Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 +/- 8.2 years [mean +/- SD], 58% women) from the Swedish registry "Senior Alert" and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non skeletal fall injury was consistently increased in T2DM with any diabetes medication. (c) 2016 American Society for Bone and Mineral Research. PMID- 27664947 TI - Ad E1A 243R oncoprotein promotes association of proto-oncogene product MYC with the NuA4/Tip60 complex via the E1A N-terminal repression domain. AB - The adenovirus E1A 243R oncoprotein targets TRRAP, a scaffold protein that assembles histone acetyltransferase (HAT) complexes, such as the NuA4/Tip60 complex which mediates transcriptional activity of the proto-oncogene MYC and helps determine the cancer cell phenotype. How E1A transforms cells through TRRAP remains obscure. We performed proteomic analysis with the N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) and showed that E1A 1-80 interacts with TRRAP, p400, and three other members of the NuA4 complex - DMAP1, RUVBL1 and RUVBL2 - not previously shown to associate with E1A 243R. E1A 1-80 interacts with these NuA4 components and MYC through the E1A TRRAP-targeting domain. E1A 243R association with the NuA4 complex was demonstrated by co immunoprecipitation and analysis with DMAP1, Tip60, and MYC. Significantly, E1A 243R promotes association of MYC/MAX with the NuA4/Tip60 complex, implicating the importance of the MYC/NuA4 pathway in cellular transformation by both MYC and E1A. PMID- 27664948 TI - Overexpression of long noncoding RNA, NEAT1 promotes cell proliferation, invasion and migration in endometrial endometrioid adenocarcinoma. AB - Long noncoding RNAs (lncRNAs) are emerging as important modulators in the biological processes and tumorigenesis. However, whether lncRNAs are involved in endometrial endometrioid adenocarcinoma (EEC) remains unclear. In the present study, we explored the expression pattern, clinical significance and biological function of nuclear enriched abundant transcript 1 (NEAT1) in EEC. The expression levels of NEAT1 were elevated in EEC tissues and cell lines, and higher expression levels of NEAT1 were positively correlated with FIGO stage and lymph node metastasis. Overexpression of NEAT1 in HEC-59 cells transfected with pGCMV NEAT1 promotes cell growth, colony formation ability as well as invasive and migratory ability; while knock-down of NEAT1 in HEC-59 cells by siNEAT1 transfection exhibited the opposite effects. Flow cytometry analysis showed that overexpression of NEAT1 led to an increase in S-phase cells and attenuated cell apoptosis, and knock-down of NEAT1 induced G0/G1 arrest and also induced cell apoptosis in HEC-59 cells. Tumor metastasis real-time PRC array showed that six metastasis-related genes (c-myc, insulin like growth factor 1(IGF1), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 7(MMP-7) were up regulated, and Cadherin 1 and TIMP metallopeptidase inhibitor 2 were down regulated) in NEAT1-overexpressing HEC-59 cells. Further qRT-PCR and western blot results confirmed that c-myc, IFG1, MMP-2 and MMP-7 were dys-regulated by NEAT1. Together, our data underscore the significance of NEAT1 in EEC development, and NEAT1 may a potential therapeutic target for EEC. PMID- 27664949 TI - Doxorubicin-loaded nanocarriers: A comparative study of liposome and nanostructured lipid carrier as alternatives for cancer therapy. AB - Nowadays cancer is one of the most common causes of deaths worldwide. Conventional antitumor agents still present various problems related to specificity for tumor cells often leading to therapeutic failure. Nanoscale particles are considered potential alternative to direct access of drugs into tumor cells, therefore increasing the drug accumulation and performance. The aim of this study was to evaluate the antitumor activity of doxorubicin (DOX)-loaded nanostructured lipid carriers (NLC) versus liposomes against a breast cancer animal experimental model. NLC-DOX and liposomes-DOX were successfully prepared and characterized. Tumor-bearing mice were divided into five groups (blank-NLC, blank-liposome, DOX, NLC-DOX, liposome-DOX). Each animal received by the tail vein four doses of antitumoral drugs (total dose, 16mg/kg), every 3 days. Antitumor efficacy was assessed by measuring 1) tumor volume, calculating the inhibitory ratio (TV-IR, see after) and 2) acquiring scintigraphic images of the tumor using doxorubicin radiolabeled with technetium-99m as an imaging tumor probe. Liposome-DOX and free DOX did not showed differences in the tumor mean volume, whereas NLC-DOX proved to be the best treatments in controlling the tumor growth. NLC-DOX showed an inhibition ration (TV-IR) of 73.5% while free DOX and liposome-DOX decreased TV-RI of 48.8% and 68.0%, respectively. Tumor was clearly visualized in controls, DOX, and liposome-DOX groups. Yet, regarding the NLC-DOX group, tumor was barely identified by the image, indicating antitumor efficacy. Moreover, both NLC and liposomes proved to be able to delay the occurrence of lung metastasis. In conclusion, results of this study indicated that NLC-DOX might be an alternative strategy to achieve an efficient antitumor activity. PMID- 27664950 TI - Anticonvulsant and neuroprotective effects of apelin-13 on pentylenetetrazole induced seizures in male rats. AB - Epilepsy is a common neurological disorder with no effective treatment or cure. Neuropeptide apelin is an endogenous ligand of angiotensin receptor-like 1 (APJ). It has been shown that apelin has protective and anti-neurodegenerative properties. This study was designed to evaluate the effect of apelin-13 on pentylenetetrazole (PTZ)-induced rat model of seizure. Adult male Wistar rats were divided into the experimental groups as follows: control group receiving PTZ; apelin-treated group which received apelin-13 before PTZ; apelin+F13A treated group which received apelin-13 plus the apelin receptor antagonist (F13A) before PTZ; apelin+naloxone group which received apelin-13+naloxone before PTZ. Behavioral scoring was used to access seizure. The expression level of APJ was measured by western blotting. Neuronal degeneration, apoptosis and astrocyte activation were evaluated by vanadium acid fuchsin (VAF) staining and immunohistochemistry. Our data demonstrated that apelin-13 pretreatment significantly inhibited seizure threshold (p<0.001) and tonic-clonic latency (p<0.001) compared with the control group. In addition, PTZ-induced up-regulation of APJ was attenuated by apelin-13 treatment. Histological and immunohistochemical findings also showed that apelin-13 could protect cortical neurons against PTZ-induced neuroinflammation and apoptosis. In conclusion, apelin-13 has anticonvulsive and neuroprotective properties against PTZ-induced seizure in rats and provided a new pharmacological aspect of the neuropeptide apelin. PMID- 27664951 TI - The influence of maternal smoking on transferrin sialylation and fetal biometric parameters. AB - OBJECTIVES: Transferrin is a glycosylated protein responsible for transporting iron, an essential metal responsible for proper fetal development. Tobacco is a heavily used xenobiotic having a negative impact on the human body and pregnancy outcomes. Aims of this study was to examine the influence of tobacco smoking on transferrin sialic acid residues and their connection with fetal biometric parameters in women with iron-deficiency. METHODS: The study involved 173 samples from pregnant women, smokers and non-smokers, iron deficient and not. Transferrin sialylation was determined by capillary electrophoresis. The cadmium (Cd) level was measured by atomic absorption and the sialic acid concentration by the resorcinol method. RESULTS: Women with iron deficiencies who smoked gave birth earlier than non-smoking, non-iron-deficient women. The Cd level, but not the cotinine level, was positively correlated with transferrin sialylation in the blood of iron-deficient women who smoked; 3-, 4-, 5- and 6-sialoTf correlated negatively with fetal biometric parameters in the same group. CONCLUSION: It has been shown the relationship between Cd from tobacco smoking and fetal biometric parameters observed only in the iron deficient group suggests an additive effect of these two factors, and indicate that mothers with anemia may be more susceptible to Cd toxicity and disturbed fetal development. PMID- 27664952 TI - Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability. AB - An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8nm) and TiO2 nanoparticles (TiO2NPs; 6nm and 35nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin 5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO2NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO2NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO2NPs in BBB. PMID- 27664954 TI - AT2 Receptors: Potential Therapeutic Targets for Hypertension. AB - The renin-angiotensin system (RAS) is arguably the most important and best studied hormonal system in the control of blood pressure (BP) and the pathogenesis of hypertension. The RAS features its main effector angiotensin II (Ang II) acting via its 2 major receptors, angiotensin type-1(AT1R) and type-2 (AT2R). In general, AT2Rs oppose the detrimental actions of Ang II via AT1Rs. AT2R activation induces vasodilation and natriuresis, but its effects to lower BP in hypertension have not been as clear as anticipated. Recent studies, however, have demonstrated that acute and chronic AT2R stimulation can induce natriuresis and lower BP in the Ang II infusion model of experimental hypertension. AT2R activation induces receptor recruitment from intracellular sites to the apical plasma membranes of renal proximal tubule cells via a bradykinin, nitric oxide, and cyclic guanosine 3',5' monophosphate signaling pathway that results in internalization and inactivation of sodium (Na+) transporters Na+-H+ exchanger-3 and Na+/K+ATPase. These responses do not require the presence of concurrent AT1R blockade and are effective both in the prevention and reversal of hypertension. This review will address the role of AT2Rs in the control of BP and Na+ excretion and the case for these receptors as potential therapeutic targets for hypertension in humans. PMID- 27664953 TI - Associations of the Serum/Glucocorticoid Regulated Kinase Genes With BP Changes and Hypertension Incidence: The Gensalt Study. AB - BACKGROUND: Single-marker and novel gene-based methods were employed to examine the associations of the serum/glucocorticoid regulated kinases (SGK) gene family with longitudinal blood pressure (BP) changes and hypertension incidence in a family-based cohort study. METHODS: Totally, 1,768 Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current analyses. Nine BP measures were obtained at each of 3 visits during the GenSalt follow-up study. Mixed-model and Gene-based analyses were used to examine the associations of the SGK gene family with longitudinal BP phenotypes. Bonferroni correction was applied to account for multiple testing. RESULTS: After an average 7.2-year follow-up, 32.2% (513) of participants free of hypertension at baseline developed hypertension. Four novel SNPs in the SGK1 gene were predictive of the longitudinal BP phenotypes. The major alleles of SGK1 rs1763498 and rs114414980 conferred 2.9- and 2.5-fold increased risks of hypertension development, respectively (P = 1.0*10-4 and 6.0*10-4, respectively). In addition, the major allele of SGK1 rs229133 was significantly associated with 0.4mm Hg larger annual increases in systolic BP (P = 4.2*10-4), while the major allele of rs6924468 was significantly associated with 0.2mm Hg smaller annual increases in diastolic BP (P = 4.2*10-4). Gene-based analyses revealed an association of the SGK1 gene with risk of hypertension development (P = 7.4*10 3). No evidence for the SGK2 and SGK3 genes was found. CONCLUSIONS: The findings of the current study suggest that the SGK1 gene may play a role in long-term BP regulation and hypertension incidence. PMID- 27664956 TI - Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor beta2. AB - STUDY QUESTION: Does chronic stress in mice accelerate the development of endometriosis, and, if so, through what mechanism? SUMMARY ANSWER: Exposure to chronic stress accelerates the development of endometriosis and exacerbates the endometriosis-associated generalized hyperalgesia, most likely through activation of the adrenoceptor beta2 (ADRB2) and cAMP responsive element-binding protein (CREB). WHAT IS KNOWN ALREADY: Women with endometriosis tend to have higher levels of psychological stress, which is known to impact negatively on health in general and to promote tumor growth and metastasis in particular. Exposure to chronic stress before and after the induction of endometriosis is reported to increase lesion sizes in rodents, but it is unclear whether adrenoceptors are involved or not in the stress-promoted development of endometriosis. STUDY DESIGN, SIZE, DURATION: Three independent, prospective, randomized mouse experimentations. A total of 184 virgin female Balb/C mice were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: In Experiment 1, the mice were randomly divided into four groups: the control group, which received no stress; the before, after and both groups, which received immobilization stress before, after and both before and after the induction of endometriosis, respectively. In Experiment 2, mice were randomly divided into four groups one day after the induction of endometriosis: phosphate buffer saline (PBS) and propranolol (PROP) groups, which received the mini-pump containing, respectively, PBS only and propranolol (a non-selective ADRB antagonist) but no stress, STR+PROP and STR+PBS groups, which received stress and the mini-pump containing, respectively, propranolol and PBS. The immobilization stress started after the insertion of mini-pumps. In Experiment 3, mice were induced with endometriosis. Three days after the induction, they were randomly divided into four groups: control, ADRAa, ADRB2a, and ADRBa, which received the mini-pump containing solution only, metaraminol (a non-specific alpha adrenoceptor agonist), tebutaline (a specific ADRB2 agonist), or isoproterenol (a non-specific ADRB agonist), respectively. In all three experiments, the bodyweight and hotplate latency were evaluated before sacrifice 14 days after the induction. In all experimentations, the lesion weight was evaluated and the harvested ectopic endometrial tissue samples were subjected to immunohistochemistry analysis of vascular endothelial growth factor (VEGF), CD31-positive microvessels, proliferating cell nuclear antigen (PCNA), phosphorylated CREB, ADRB1, ADRB2, ADRB3, adrenergic receptor alpha1 (ADRA1) and ADRA2. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to chronic stress accelerated the development of endometriosis and exacerbated the endometriosis associated generalized hyperalgesia. This promotional effect is likely to be mediated through the systemic activation of the sympatho-adreno-medullary (SAM) axis, which results in subsequent release of catecholamines. The surging catecholamines may activate ADRB2 and CREB, yielding increased angiogenesis and cellular proliferation in ectopic endometrium in mice with induced endometriosis. In addition, beta adrenergic receptor blockade completely abolished the promotional effect of chronic stress, likely through suppression of ADRB2 and CREB activation, thus suppressing angiogenesis and proliferation. Moreover, a non specific adrenergic beta agonist and a specific adrenergic beta2 agonist, but not non-specific adrenergic alpha agonist, acted similarly to chronic stress, accelerating the development of endometriosis and exacerbating the generalized hyperalgesia in mice with pre-existing endometriosis. LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of immunohistochemistry analyses only and the lack of molecular data. WIDER IMPLICATIONS OF THE FINDINGS: The present study provides the experimental evidence that chronic stress can promote the development of endometriosis through the activation of ADRB2. Given ADRB2 is also expressed in human endometriosis and appears to be functional, and in light of recent awareness that adrenergic signaling plays critical roles in tumorigenesis, it is likely that adrenergic signaling may play important roles in the development of endometriosis and is potentially a target for intervention. STUDY FUNDING/COMPETING INTERESTS: This research was supported in part by grants (81270676, 81471434 and 81530040 to S.W.G.; 81370695 and 81671436 to X.S.L.) from the National Natural Science Foundation of China, and grant (2013ZYJB0019 to X.S.L.) from Shanghai Municipal Commission of Health and Family Planning. None of the authors has anything to disclose. PMID- 27664955 TI - Pregnancy outcome in women with endometriosis achieving pregnancy with IVF. AB - STUDY QUESTION: Are women with endometriosis who conceive with IVF at increased risk of preterm birth? SUMMARY ANSWER: Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. WHAT IS KNOWN ALREADY: The eutopic endometrium of women with endometriosis has been repeatedly shown to present molecular and cellular alterations. On this basis, it has been hypothesized that pregnancy outcome may be altered in affected women. However, to date, available evidence from epidemiological studies is scanty and conflicting. Data tended to be partly consistent only for an increased risk of preterm birth and placenta previa. STUDY DESIGN, SIZE, DURATION: Retrospective matched case control study of women achieving an IVF singleton pregnancy progressing beyond 12 weeks' gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women achieving IVF singleton pregnancies that progressed beyond 12 weeks' gestation at two infertility units were reviewed. Cases were women with a history of surgery for endometriosis and/or with a sonographic diagnosis of the disease at the time of the IVF cycle. Controls were women without current or past evidence of endometriosis who were matched to cases by age (+/- 6 months), type of cycle (fresh or frozen cycle) and study period. Male factor and unexplained infertility were the most common diagnoses in the control group. Two hundred and thirty-nine women with endometriosis and 239 controls were selected. The main outcome of the study was the rate of preterm birth (birth < 37 weeks' gestation) regardless of the cause. Secondary analyses were performed for the most common obstetrical complications. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of preterm birth was similar in the two study groups (14% and 14%, respectively, p = 0.89). The rate of live birth and the incidence of hypertensive disorders, gestational diabetes, small and large for gestational age newborns and neonatal problems also did not differ. In contrast, placenta previa was more common in women with endometriosis than controls (6% versus 1%, respectively; p = 0.006): The adjusted odds ratio was 4.8 (95% confidence interval: 1.4-17.2). LIMITATIONS, REASONS FOR CAUTION: As for all observational studies, confounders cannot be totally excluded. Moreover, the retrospective study design exposes the findings to some inaccuracies. For example, the independent role of adenomyosis could not be reliably assessed because this diagnosis is complex and would necessitate a prospective recruitment. Second, the selection of controls may also be a matter of concern because some affected women may have been erroneously included in this group. Third, even if the sample size is significant, it is insufficient for robust subgroup analyses. Finally, it is mandatory to point out that our conclusions are valid for IVF pregnancies only, and specific data from properly designed studies are required to support any inference for natural pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study suggest that women with endometriosis conceiving with IVF can be reassured regarding the risk of preterm birth. The observed association with placenta previa requires further investigation and may open a new avenue of research. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. None of the authors have any conflict of interest to declare. PMID- 27664957 TI - Identification of successive flowering phases highlights a new genetic control of the flowering pattern in strawberry. AB - The genetic control of the switch between seasonal and perpetual flowering has been deciphered in various perennial species. However, little is known about the genetic control of the dynamics of perpetual flowering, which changes abruptly at well-defined time instants during the growing season. Here, we characterize the perpetual flowering pattern and identify new genetic controls of this pattern in the cultivated strawberry. Twenty-one perpetual flowering strawberry genotypes were phenotyped at the macroscopic scale for their course of emergence of inflorescences and stolons during the growing season. A longitudinal analysis based on the segmentation of flowering rate profiles using multiple change-point models was conducted. The flowering pattern of perpetual flowering genotypes takes the form of three or four successive phases: an autumn-initiated flowering phase, a flowering pause, and a single stationary perpetual flowering phase or two perpetual flowering phases, the second one being more intense. The genetic control of flowering was analysed by quantitative trait locus mapping of flowering traits based on these flowering phases. We showed that the occurrence of a fourth phase of intense flowering is controlled by a newly identified locus, different from the locus FaPFRU, controlling the switch between seasonal and perpetual flowering behaviour. The role of this locus was validated by the analysis of data obtained previously during six consecutive years. PMID- 27664958 TI - 3D deformation field in growing plant roots reveals both mechanical and biological responses to axial mechanical forces. AB - Strong regions and physical barriers in soils may slow root elongation, leading to reduced water and nutrient uptake and decreased yield. In this study, the biomechanical responses of roots to axial mechanical forces were assessed by combining 3D live imaging, kinematics and a novel mechanical sensor. This system quantified Young's elastic modulus of intact poplar roots (32MPa), a rapid <0.2 mN touch-elongation sensitivity, and the critical elongation force applied by growing roots that resulted in bending. Kinematic analysis revealed a multiphase bio-mechanical response of elongation rate and curvature in 3D. Measured critical elongation force was accurately predicted from an Euler buckling model, indicating that no biologically mediated accommodation to mechanical forces influenced bending during this short period of time. Force applied by growing roots increased more than 15-fold when buckling was prevented by lateral bracing of the root. The junction between the growing and the mature zones was identified as a zone of mechanical weakness that seemed critical to the bending process. This work identified key limiting factors for root growth and buckling under mechanical constraints. The findings are relevant to crop and soil sciences, and advance our understanding of root growth in heterogeneous structured soils. PMID- 27664959 TI - Orthographic and Phonological Representations in the Fusiform Cortex. AB - Mental and neural representations of words are at the core of understanding the cognitive and neural mechanisms of reading. Despite extensive studies, the nature of visual word representation remains highly controversial due to methodological limitations. In particular, it is unclear whether the fusiform cortex contains only abstract orthographic representation, or represents both lower and higher level orthography as well as phonology. Using representational similarity analysis, we integrated behavioral ratings, computational models of reading and visual object recognition, and neuroimaging data to examine the nature of visual word representations in the fusiform cortex. Our results provided clear evidence that the middle and anterior fusiform represented both phonological and orthographic information. Whereas lower level orthographic information was represented at every stage of the ventral visual stream, abstract orthographic information was increasingly represented along the posterior-to-anterior axis. Furthermore, the left and right hemispheres were tuned to high- and low-frequency orthographic information, respectively. These results help to resolve the long standing debates regarding the role of the fusiform in reading, and have significant implications for the development of psychological, neural, and computational theories of reading. PMID- 27664960 TI - The Large-Scale Organization of Object-Responsive Cortex Is Reflected in Resting State Network Architecture. AB - Neural responses to visually presented objects have a large-scale spatial organization across the cortex, related to the dimensions of animacy and object size. Most proposals about the origins of this organization point to the influence of differential connectivity with other cortical regions as the key organizing force that drives distinctions in object-responsive cortex. To explore this possibility, we used resting-state functional connectivity to examine the relationship between stimulus-evoked organization of objects, and distinctions in functional network architecture. Using a data-driven analysis, we found evidence for three distinct whole-brain resting-state networks that route through object responsive cortex, and these naturally manifest the tripartite structure of the stimulus-evoked organization. However, object-responsive regions were also highly correlated with each other at rest. Together, these results point to a nested network architecture, with a local interconnected network across object responsive cortex and distinctive subnetworks that specifically route these key object distinctions to distinct long-range regions. Broadly, these results point to the viability that long-range connections are a driving force of the large scale organization of object-responsive cortex. PMID- 27664963 TI - Where does TMS Stimulate the Motor Cortex? Combining Electrophysiological Measurements and Realistic Field Estimates to Reveal the Affected Cortex Position. AB - Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our study is one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for 2 hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS. PMID- 27664964 TI - Balancing the 2 Hemispheres in Simple Calculation: Evidence From Direct Cortical Electrostimulation. AB - How do the parietal lobes contribute to simple calculation? Clinical and neuroimaging methods, which are based mainly on correlational evidence, have provided contrasting results so far. Here we used direct cortical electrostimulation during brain surgery to causally infer the role of the left and right parietal lobes in simple calculation. Stimulation provoked errors for addition and multiplication in different parietal areas on both hemispheres. Crucially, an innovative qualitative error analysis unveiled the functional contrast of the 2 parietal lobes. Right or left stimulation led to different types of substitution errors in multiplication, unveiling the function of the more active hemisphere. While inhibition of the left hemisphere led mainly to approximation errors, right hemisphere inhibition enhanced retrieval within a stored repertory. These results highlight the respective roles of each hemisphere in the network: rote retrieval of possible solutions by the left parietal areas and approximation to the correct solution by the right hemisphere. The bilateral orchestration between these functions guarantees precise calculation. PMID- 27664961 TI - Prenatal Maternal Cortisol Has Sex-Specific Associations with Child Brain Network Properties. AB - Elevated maternal cortisol concentrations have the potential to alter fetal development in a sex-specific manner. Female brains are known to show adaptive behavioral and anatomical flexibility in response to early-life exposure to cortisol, but it is not known how these sex-specific effects manifest at the whole-brain structural networks. A prospective longitudinal study of 49 mother child dyads was conducted with serial assessments of maternal cortisol levels from 15 to 37 gestational weeks. We modeled the structural network of typically developing children (aged 6-9 years) and examined its global connectome properties, rich-club organization, and modular architecture. Network segregation was susceptible only for girls to variations in exposure to maternal cortisol during pregnancy. Girls generated more connections than boys to maintain topologically capable and efficient neural circuits, and this increase in neural cost was associated with higher levels of internalizing problems. Maternal cortisol concentrations at 31 gestational weeks gestation were most strongly associated with altered neural connectivity in girls, suggesting a sensitive period for the maternal cortisol-offspring brain associations. Our data suggest that girls exhibit an adaptive response by increasing the neural network connectivity necessary for maintaining homeostasis and efficient brain function across the lifespan. PMID- 27664965 TI - Distinct Corticostriatal and Intracortical Pathways Mediate Bilateral Sensory Responses in the Striatum. AB - Individual striatal neurons integrate somatosensory information from both sides of the body, however, the afferent pathways mediating these bilateral responses are unclear. Whereas ipsilateral corticostriatal projections are prevalent throughout the neocortex, contralateral projections provide sparse input from primary sensory cortices, in contrast to the dense innervation from motor and frontal regions. There is, therefore, an apparent discrepancy between the observed anatomical pathways and the recorded striatal responses. We used simultaneous in vivo whole-cell and extracellular recordings combined with focal cortical silencing, to dissect the afferent pathways underlying bilateral sensory integration in the mouse striatum. We show that unlike direct corticostriatal projections mediating responses to contralateral whisker deflection, responses to ipsilateral stimuli are mediated mainly by intracortical projections from the contralateral somatosensory cortex (S1). The dominant pathway is the callosal projection from contralateral to ipsilateral S1. Our results suggest a functional difference between the cortico-basal ganglia pathways underlying bilateral sensory and motor processes. PMID- 27664962 TI - N-Methyl d-Aspartate Receptor Expression Patterns in the Human Fetal Cerebral Cortex. AB - N-methyl d-aspartate receptors (NMDARs), a subtype of glutamate receptor, have important functional roles in cellular activity and neuronal development. They are well-studied in rodent and adult human brains, but limited information is available about their distribution in the human fetal cerebral cortex. Here we show that 3 NMDAR subunits, NR1, NR2A, and NR2B, are expressed in the human cerebral cortex during the second trimester of gestation, a period of intense neurogenesis and synaptogenesis. With increasing fetal age, expression of the NMDAR-encoding genes Grin1 (NR1) and Grin2a (NR2A) increased while Grin2b (NR2B) expression decreased. The protein levels of all 3 subunits paralleled the changes in gene expression. On cryosections, all 3 subunits were expressed in proliferative ventricular and subventricular zones, in radial glia, and in intermediate progenitor cells, consistent with their role in the proliferation of cortical progenitor cells and in the determination of their respective fates. The detection of NR1, NR2A, and NR2B in both glutamatergic and GABAergic neurons of the cortical plate suggests the involvement of NMDARs in the maturation of human cortical neurons and in early synapse formation. Our results and previous studies in rodents suggest that NMDAR expression in the developing human brain is evolutionarily conserved. PMID- 27664966 TI - Neural Population Decoding Reveals the Intrinsic Positivity of the Self. AB - People are motivated to hold favorable views of themselves, which manifests as a positivity bias when evaluating their own performance and abilities. However, it remains an open question whether positive affect is an essential component of people's self-concept. Prior functional neuroimaging research demonstrated that similar regions of the brain support positive affect and self-referential processing, although a direct test of their shared representation has yet to be examined. Here we use functional magnetic resonance imaging in conjunction with multivariate pattern analysis in a cross-domain neural population decoding paradigm. We found that a multivariate pattern classifier model trained to dissociate neural responses to viewing positively and negatively valenced images can dissociate thinking about oneself from a close friend during a lexical trait judgment task commonly used in the study of self-referential processing. Cross domain classification accuracy was found to be highest in the ventral medial prefrontal cortex (vMPFC), a region previously implicated in both self referential processing and positive affect. These results show that brain responses during self-referential processing can be decoded from multi-voxel activation patterns in the vMPFC when viewing positively valenced material, thereby providing evidence that positive affect may be a central component of the mental representation of the self. PMID- 27664967 TI - Comparison of In Vivo and Ex Vivo MRI of the Human Hippocampal Formation in the Same Subjects. AB - Multiple techniques for quantification of hippocampal subfields from in vivo MRI have been proposed. Linking in vivo MRI to the underlying histology can help validate and improve these techniques. High-resolution ex vivo MRI can provide an intermediate modality to map information between these very different imaging modalities. This article evaluates the ability to match information between in vivo and ex vivo MRI in the same subjects. We perform rigid and deformable registration on 10 pairs of in vivo (3 T, 0.4 * 0.4 * 2.6 mm3) and ex vivo (9.4 T, 0.2 * 0.2 * 0.2 mm3) scans, and describe differences in MRI appearance between these modalities qualitatively and quantitatively. The feasibility of using this dataset to validate in vivo segmentation is evaluated by applying an automatic hippocampal subfield segmentation technique (ASHS) to in vivo scans and comparing SRLM (stratum/radiatum/lacunosum/moleculare) surface to manual tracing on corresponding ex vivo scans (and in 2 cases, histology). Regional increases in thickness are detected in ex vivo scans adjacent to the ventricles and were not related to scanner, resolution differences, or susceptibility artefacts. Satisfactory in vivo/ex vivo registration and subvoxel accuracy of ASHS segmentation of hippocampal SRLM demonstrate the feasibility of using this dataset for validation, and potentially, improvement of in vivo segmentation methods. PMID- 27664969 TI - Long-term adherence to topical psoriasis treatment can be abysmal: a 1-year randomized intervention study using objective electronic adherence monitoring. AB - BACKGROUND: Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short-term adherence. Psoriasis is a chronic disease, and long-term adherence is an even bigger problem. OBJECTIVES: To determine how well medication is used in the long-term topical treatment of psoriasis and to assess the potential of an internet-based reporting intervention to improve treatment adherence and outcomes. METHODS: An investigator-blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild-to-moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard-of-care or internet-based reporting group. Adherence was objectively monitored with Medication Event Monitoring System(r) caps. RESULTS: Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard of-care group (50% vs. 35%, P = 0.08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1.61 vs. -0.12, P = 0.003), month 3 (2.50 vs. 0.79, P = 0.025) and month 12 (3.32 vs. 0.34, P = 0.038) than in the standard-of-care group. CONCLUSIONS: This study likely underestimates the challenge of long-term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients' treatment outcomes. PMID- 27664968 TI - Prefrontal Volume Mediates Effect of COMT Polymorphism on Interference Resolution Capacity in Healthy Male Adults. AB - There exist gender differences in the modulation of catechol-O-methyltransferase (COMT) Val158Met polymorphism on cognitive performance; however, the underlying gene-anatomy-cognition pathways remain unknown. Here we hypothesize that prefrontal volume may mediate the modulation of COMT Val158Met polymorphism on interference resolution capacity in a gender-dependent manner. In 261 healthy young human subjects (143 males and 118 females), a 2-way analysis of variance showed a COMT * gender interaction (P = 0.023) on interference resolution capacity. Val/Val subjects performed worse in Stroop interference test than Met/Met subjects only in males (P = 0.028). Voxel-wise analysis in the whole brain also exhibited a COMT * gender interaction on gray matter volume (GMV) in the left lateral frontal pole (FP). Val/Val male individuals exhibited significantly decreased GMV in the left lateral FP than Val/Met (P = 0.003) and Met/Met (P = 0.006) male carriers. Mediation analysis revealed that the GMV of the left lateral FP mediated the association between COMT polymorphism and interference resolution in males. These findings provide a gene-anatomy-cognition pathway to describe how COMT Val158Met polymorphism affects interference resolution capacity via modulating the prefrontal GMV in healthy male subjects. PMID- 27664970 TI - Intravoxel incoherent motion diffusion-weighted imaging for characterizing focal hepatic lesions: Correlation with lesion enhancement. AB - PURPOSE: To evaluate the value of intravoxel incoherent motion (IVIM) parameters for characterizing focal hepatic lesions, and to assess the correlation between IVIM parameters and arterial nodule enhancement. MATERIALS AND METHODS: We retrospectively evaluated 161 lesions (91 hepatocellular carcinomas [HCCs], 27 intrahepatic cholangiocarcinomas [IHCCs], 20 hemangiomas, 9 combined hepatocellular-cholangiocarcinomas, 9 metastases, and 5 other tumors) in 161 patients (105 men and 56 women; mean age, 56.4 years). Diffusion-weighted imaging was performed using nine b-values (0-900 s/mm2 ) at 1.5T. Apparent diffusion coefficient (ADC), molecular diffusion coefficient (Dslow ), perfusion fraction (f), and perfusion-related diffusion coefficient (Dfast ) were compared among the hepatic lesions using analysis of variance (ANOVA). Receiver-operating characteristic analysis was performed to assess diagnostic performance. The enhancement fraction (EF) and the relative enhancement (RE) of the hepatic lesions on arterial phase gadoxetic acid-enhanced images were correlated with the IVIM parameters using Spearman's test. RESULTS: For the differentiation of hemangiomas from malignant tumors, Dslow showed the largest area under the curve (0.933) among all parameters. Although ADC did not show any difference among malignant lesions (P >= 0.28), HCCs showed a significantly lower Dslow than IHCC (P < 0.001) and a higher f than did IHCC (P < 0.001) and metastasis (P = 0.027); f had a significant positive correlation with EF (r = 0.420, P < 0.001) and RE (r = 0.264, P = 0.001). CONCLUSION: IVIM parameters are more helpful in characterizing malignant hepatic lesions than ADC; f may reflect the extent and degree of hepatic nodule enhancement in the arterial phase, and may allow for differentiation of HCC from IHCC and metastasis. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1589-1598. PMID- 27664971 TI - Characterization of peptides from common bean protein isolates and their potential to inhibit markers of type-2 diabetes, hypertension and oxidative stress. AB - BACKGROUND: Diabetes and hypertension are diseases affecting a high proportion of the world population; the use of food-based products such as common bean peptides may contribute to reduce the risk of complications associated to chronic diseases. The aim was to produce and characterize peptides from common bean protein isolates and evaluate their potential to inhibit markers of type-2 diabetes, hypertension and oxidative stress. RESULTS: Mexican black and Brazilian Carioca bean isolated proteins were characterized after pepsin/pancreatin digestion. Also, four synthesized pure peptides, originally found in these beans, were evaluated. Bean protein digests and pure peptides exerted dipeptidyl peptidase-IV (DPP-IV) inhibition (IC50 = 0.03-0.87 mg dry weight (DW) mL-1 ). Lineweaver-Burk plots and computational modeling showed competitive inhibition of DPP-IV. Angiotensin-converting enzyme (ACE) inhibition ranged from IC50 = 0.09 to 0.99 mg DW mL-1 , and alpha-glucosidase inhibition ranged from 36.3 to 50.1% mg-1 DW. Carioca Perola bean digested proteins presented the highest antioxidant capacity (269.3 mmol L-1 Trolox equivalent g-1 DW) as the peptide KTYGL (P > 0.05) with the most potent DPP-IV and ACE inhibition. CONCLUSION: Peptides from common bean have antidiabetic and antihypertensive potential regardless of their antioxidant capacity. (c) 2016 Society of Chemical Industry. PMID- 27664972 TI - Relationships between varus-valgus laxity of the severely osteoarthritic knee and gait, instability, clinical performance, and function. AB - Increased varus-valgus laxity has been reported in individuals with knee osteoarthritis (OA) compared to controls. However, the majority of previous investigations may not report truly passive joint laxity, as their tests have been performed on conscious participants who could be guarding against motion with muscle contraction during laxity evaluation. The purpose of this study was to investigate how a measure of passive knee laxity, recorded when the participant is under anesthesia, is related to varus-valgus excursion during gait, clinical measures of performance, perceived instability, and self-reported function in participants with severe knee OA. We assessed passive varus-valgus knee laxity in 29 participants (30 knees) with severe OA, as they underwent total knee arthroplasty (TKA). Participants also completed gait analysis, clinical assessment of performance (6-min walk (6 MW), stair climbing test (SCT), isometric knee strength), and self-reported measures of function (perceived instability, Knee injury, and Osteoarthritis Outcome Score (KOOS) a median of 18 days before the TKA procedure. We observed that greater passive varus-valgus laxity was associated with greater varus-valgus excursion during gait (R2 = 0.34, p = 0.002). Significant associations were also observed between greater laxity and greater isometric knee extension strength (p = 0.014), farther 6 MW distance (p = 0.033) and shorter SCT time (p = 0.046). No relationship was observed between passive varus-valgus laxity and isometric knee flexion strength, perceived instability, or any KOOS subscale. The conflicting associations between laxity, frontal excursion during gait, and functional performance suggest a complex relationship between laxity and knee cartilage health, clinical performance, and self-reported function that merits further study. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1644-1652, 2017. PMID- 27664973 TI - Metabolic profile of injured human spinal cord determined using surface microdialysis. AB - The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self-organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure. A Kohonen map, which is an unsupervised, self organizing topology-preserving neural network, was used to analyze 3366 h of monitoring data. We first visualized the different spinal cord metabolic states. Our data show that the injured cord assumes one or more of four metabolic states. On the basis of their metabolite profiles, we termed these states near-normal, ischemic, hypermetabolic, and distal. We then visualized how patients' intraspinal pressure and spinal cord perfusion pressure affect spinal cord metabolism. This revealed that for more than 60% of the time, spinal cord metabolism is patient-specific; periods of high intraspinal pressure or low perfusion pressure are not associated with specific spinal cord metabolic patterns. Finally, we determined relationships between spinal cord metabolism and neurological status. Patients with complete deficits have shorter periods of near normal spinal cord metabolic states (7 +/- 4% vs. 58 +/- 12%, p < 0.01, mean +/- standard error) and more variable injury site metabolic responses (metabolism spread in 70 +/- 11 vs. 40 +/- 6 hexagons, p < 0.05), compared with patients who have incomplete neurological deficits. We conclude that Kohonen maps allow us to visualize the metabolic responses of the injured spinal cord and may thus aid us in treating patients with acute spinal cord injuries. PMID- 27664974 TI - Kidney Transplantation From a Donor With Sickle Cell Disease. AB - In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37-year-old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies. PMID- 27664975 TI - Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients. AB - BACKGROUND: Chronic lymphocytic leukaemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, particularly cutaneous squamous cell carcinoma (cSCC), but little is known about cSCC incidence in Australasian CLL patients. AIM: In this retrospective study, we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ). METHODS: We retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who presented to the Haematology Department, Christchurch Hospital, NZ during the period 1996-2015. Baseline characteristics, incidence of second cancers, treatment details and overall survival were analysed. RESULTS: During follow-up (median = 11.8 years), 221 second cancers were recorded in 88 patients. Of these cancers, 185 were cSCC, removed from 61 patients. In 56% of these patients, >1 cSCC was removed, and the majority of cSCC occurred following the treatment for CLL. The cumulative incidence of a first cSCC was 11% at 5 years, whereas the cumulative incidence of a subsequent cSCC was 88% at 5 years. The incidence of cSCC in male patients was threefold higher than that reported for the general NZ population. CONCLUSION: NZ CLL patients have a high incidence of cSCC relative to the levels observed in the general population, which are themselves among the highest in the world. The careful monitoring of CLL patients is warranted, particularly those who have a progressive disease or have had a first cSCC removed. PMID- 27664976 TI - Genome scan reveals selection acting on genes linked to stress response in wild pearl millet. AB - Uncovering genomic regions involved in adaption is a major goal in evolutionary biology. High-throughput sequencing now makes it possible to tackle this challenge in nonmodel species. Yet, despite the increasing number of methods targeted to specifically detect genomic footprints of selection, the complex demography of natural populations often causes high rates of false positive in gene discoveries. The aim of this study was to identify climate adaptations in wild pearl millet populations, Cenchrus americanus ssp. monodii. We focused on two climate gradients, one in Mali and one in Niger. We used a two-step strategy to limit false-positive outliers. First, we considered gradients as biological replicates and performed RNA sequencing of four populations at the extremities. We combined four methods-three based on differentiation among populations and one based on diversity patterns within populations-to identify outlier SNPs from a set of 87 218 high-quality SNPs. Among 11 155 contigs of pearl millet reference transcriptome, 540 exhibited selection signals as evidenced by at least one of the four methods. In a second step, we genotyped 762 samples in 11 additional populations distributed along the gradients using SNPs from the detected contigs and random SNPs as control. We further assessed selection on this large data set using a differentiation-based method and a method based on correlations with environmental variables based. Four contigs displayed consistent signatures between the four extreme and 11 additional populations, two of which were linked to abiotic and biotic stress responses. PMID- 27664977 TI - miR-370 suppresses HBV gene expression and replication by targeting nuclear factor IA. AB - Hepatitis B virus (HBV) infection is a major health problem worldwide. The roles of microRNAs in the regulation of HBV expression are being increasingly recognized. In this study, we found that overexpression of miR-370 suppressed HBV gene expression and replication in Huh7 cells, whereas antisense knockdown of endogenous miR-370 enhanced HBV gene expression and replication in Huh7 cells and HepG2.2.15 cells. Further, we identified the transcription factor nuclear factor IA (NFIA) as a new host target of miR-370. Overexpression and knockdown studies showed that NFIA stimulated HBV gene expression and replication. Importantly, overexpression of NFIA counteracted the effect of miR-370 on HBV gene expression and replication. Further mechanistic studies showed that miR-370 suppressed HBV replication and gene expression by repressing HBV Enhancer I activity, and one of the NFIA binding site in the Enhancer I element was responsible for the repressive effect of miR-370 on HBV Enhancer I activity. Altogether, our results demonstrated that miR-370 suppressed HBV gene expression and replication through repressing NFIA expression, which stimulates HBV replication via direct regulation on HBV Enhancer I activities. Our findings may provide a new antiviral strategy for HBV infection. J. Med. Virol. 89:834-844, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27664978 TI - Early, focal changes in cartilage cellularity and structure following surgically induced meniscal destabilization in the mouse. AB - Post-traumatic osteoarthritis (PTOA) is an accelerated form of osteoarthritic cartilage degeneration affecting approximately 20-50% of patients experiencing joint injury. Currently PTOA is incurable; to better understand the etiology of PTOA and to develop rational anti-osteoarthritic therapies, it is critical to understand the spatiotemporal initiation and the progression of PTOA. In this study, we employed semi-quantitative histological scoring and quantitative damage analysis to examine disease progression in the murine destabilization of the medial meniscus (DMM) model of PTOA from early (3 days) through late- (112 days) disease timepoints. We observed significant, progressive articular cartilage (AC) cellular, and structural changes in the medial compartments of injured joints as early as 3 days. Spatially within the joint, cartilage damage (erosions) were observed anteriorly at 84 days. Furthermore, a drastic loss in chondrocyte number (by 3 days), surface damage (at 7 days), and cartilage erosion (at 84 days) was found to co-localize to the specific region of the medial tibial plateau AC that experienced a change in meniscal coverage due to meniscal extrusion following DMM. Taken together, these results suggest that DMM-mediated extrusion of the medial meniscus leads to rapid, spatially dependent changes in AC cellularity and structure, and precipitates the focal degeneration of cartilage associated with PTOA. Importantly, this study suggests that joint instability injuries may trigger immediate (<3 days) processes within a small population of chondrocytes that directs the initiation and progression of PTOA, and that development of chondroprotective strategies for preventing and/or delaying PTOA-related cartilage degeneration are best targeted toward these immediately early processes following joint injury. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:537-547, 2017. PMID- 27664980 TI - Alternative clamp loaders/unloaders. AB - Each time a cell duplicates, the whole genome must be accurately copied and distributed. The enormous amount of DNA in eukaryotic cells requires a high level of coordination between polymerases and other DNA and chromatin-interacting proteins to ensure timely and accurate DNA replication and chromatin formation. PCNA forms a ring that encircles the DNA. It serves as a processivity factor for DNA polymerases and as a landing platform for different proteins that interact with DNA and chromatin. It thus serves as a signaling hub and influences the rate and accuracy of DNA replication, the r-formation of chromatin in the wake of the moving fork and the proper segregation of the sister chromatids. Four different, conserved, protein complexes are in charge of loading/unloading PCNA and similar molecules onto DNA. Replication factor C (RFC) is the canonical complex in charge of loading PCNA, the replication clamp, during S-phase. The Rad24, Ctf18 and Elg1 proteins form complexes similar to RFC, with particular functions in the cell's nucleus. Here we summarize our current knowledge about the roles of these important factors in yeast. PMID- 27664979 TI - Determinants of longitudinal health-related quality-of-life change in children with asthma from low-income families: a report from the PROMIS(r) Pediatric Asthma Study. AB - BACKGROUND: How the longitudinal asthma control status and other socio demographic factors influence the changes of health-related quality of life (HRQOL) among asthmatic children, especially from low-income families, has not been fully investigated. OBJECTIVES: This study aimed to describe the trajectories of asthma-specific HRQOL over 15 months and examine the effect of asthma control status on HRQOL by taking socio-demographic factors into consideration. METHODS: A total of 229 dyads of asthmatic children and their parents enroled in public insurance programs were recruited for assessing asthma control status and HRQOL over four time points of assessment. Asthma control status was measured using the Asthma Control and Communication Instrument, and asthma-specific HRQOL was assessed using the Patient-Reported Outcomes Measurement Information System's Pediatric Asthma Impact Scale. Latent growth models (LGMs) were applied to examine the trajectory of HRQOL and the factors contributing to the changes of HRQOL. RESULTS: Unconditional LGM revealed that HRQOL was improved over time. Conditional LGM suggested that accounting for asthma control and participants' socio-demographic factors, the variation in the initial level of HRQOL was significant, yet the rate of change was not. Conditional LGM also revealed that poorly controlled asthma status was associated with poor HRQOL at each time point (P's < 0.05). Lower parental education was associated with lower baseline HRQOL (P < 0.05). Hispanic children had a larger increase in HRQOL over time (P < 0.01) than non-Hispanic White children. CONCLUSIONS: Vulnerable socio-demographic characteristics and poorly controlled asthma status affect HRQOL in children. This finding encourages interventions to improve asthma control status and HRQOL in minority children. PMID- 27664982 TI - Medical decisions are independent of cognitive impairment in amyotrophic lateral sclerosis. PMID- 27664981 TI - Associations between education and brain structure at age 73 years, adjusted for age 11 IQ. AB - OBJECTIVE: To investigate how associations between education and brain structure in older age were affected by adjusting for IQ measured at age 11. METHODS: We analyzed years of full-time education and measures from an MRI brain scan at age 73 in 617 community-dwelling adults born in 1936. In addition to average and vertex-wise cortical thickness, we measured total brain atrophy and white matter tract fractional anisotropy. Associations between brain structure and education were tested, covarying for sex and vascular health; a second model also covaried for age 11 IQ. RESULTS: The significant relationship between education and average cortical thickness (beta = 0.124, p = 0.004) was reduced by 23% when age 11 IQ was included (beta = 0.096, p = 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy. CONCLUSIONS: The association between years of education and brain structure ~60 years later was restricted to cortical thickness in this sample; however, the previously reported associations between longer education and a thicker cortex are likely to be overestimates in terms of both magnitude and distribution. This finding has implications for understanding, and possibly ameliorating, life-course brain health. PMID- 27664984 TI - Closing in on an infectious etiology of motor neuron disease. PMID- 27664983 TI - HIV-associated motor neuron disease: HERV-K activation and response to antiretroviral therapy. AB - OBJECTIVE: To determine whether there is activation of human endogenous retrovirus K (HERV-K) in amyotrophic lateral sclerosis in HIV infection and whether it might respond to treatment with antiretroviral drugs. METHODS: In this case series, we present 5 patients with HIV infection who subsequently developed motor neuron disease involving both upper and lower motor neurons. We monitored HERV-K levels in plasma of 4 of these patients. RESULTS: Three patients who received antiretroviral therapy had reversal of symptoms within 6 months of onset of neurologic symptoms and the other 2 had slow neurologic progression over several years. Three patients in whom the levels were measured at onset of neurologic symptoms showed elevated HERV-K levels that responded to optimization of antiretroviral therapy for CNS penetration. CONCLUSIONS: Thus, motor neuron disease in individuals with HIV infection may a treatable entity, but early treatment with CNS-penetrating antiretroviral therapy may be necessary. Monitoring of HERV-K levels may help guide treatment. PMID- 27664986 TI - CADASIL, CARASIL, CARASAL: The linguistic subtleties of cerebral small vessel disease. PMID- 27664985 TI - Therapeutic coma for status epilepticus: Differing practices in a prospective multicenter study. AB - OBJECTIVE: Our aim was to analyze and compare the use of therapeutic coma (TC) for refractory status epilepticus (SE) across different centers and its effect on outcome. METHODS: Clinical data for all consecutive adults (>16 years) with SE of all etiologies (except postanoxic) admitted to 4 tertiary care centers belonging to Harvard Affiliated Hospitals (HAH) and the Centre Hospitalier Universitaire Vaudois (CHUV) were prospectively collected and analyzed for TC details, mortality, and duration of hospitalization. RESULTS: Two hundred thirty-six SE episodes in the CHUV and 126 in the HAH were identified. Both groups were homogeneous in demographics, comorbidities, SE characteristics, and Status Epilepticus Severity Score (STESS); TC was used in 25.4% of cases in HAH vs 9.75% in CHUV. After adjustment, TC use was associated with younger age, lower Charlson Comorbidity Index, increasing SE severity, refractory SE, and center (odds ratio 11.3 for HAH vs CHUV, 95% confidence interval 2.47-51.7). Mortality was associated with increasing Charlson Comorbidity Index and STESS, etiology, and refractory SE. Length of stay correlated with STESS, etiology, refractory SE, and use of TC (incidence rate ratio 1.6, 95% confidence interval 1.22-2.11). CONCLUSIONS: Use of TC for SE treatment seems markedly different between centers from the United States and Europe, and did not affect mortality considering the whole cohort. However, TC may increase length of hospital stay and related costs. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with SE, TC does not significantly affect mortality. The study lacked the precision to exclude an important effect of TC on mortality. PMID- 27664987 TI - Hand postures in primary and secondary generalized tonic-clonic seizures. AB - OBJECTIVE: To evaluate and identify the frequency of hand postures during generalized convulsions in patients with genetic generalized epilepsy (GGE), localization-related epilepsy (LRE), and nonepileptic attacks (NEA). METHODS: We retrospectively analyzed 98 consecutive videos of generalized convulsions in 62 patients who were admitted for diagnostic video-EEG monitoring. Demographics were recorded, and hand postures were subdivided into fanning, fisting, index-finger pointing (IFP), clawing, and flaccid posturing. Hand postures were then compared between patients with GGE, LRE, and NEA for each stage of the convulsion and for the whole event. RESULTS: In patients with LRE, 96% had IFP, where fanning occurred in 91.3% of GGE (and only at onset), and the flaccid hand posture occurred in 56.0% of NEA. Fisting, fanning, and IFP postures all occurred significantly more frequently during epileptic seizures than during NEA (74.0% vs 32.0%, p = 0.0003; 60.3% vs 20.0%, p = 0.0005; 83.6% vs 12.0%, p < 0.0001). The claw hand posture was present only during NEA, and the flaccid posture occurred significantly more frequently during NEA than during epileptic seizures (56.0% vs 15.1%, p = 0.0001). CONCLUSIONS: Distinct ictal hand or finger posturing is present in patients with GGE, LRE, and NEA. The presence of any fisting, fanning, clawing, IFP, or flaccid hand posturing can help distinguish epileptic seizures from NEA. IFP suggests LRE while fanning with evolution suggests GGE. Overall, hand posturing during seizures provides unique information and aids in the differential diagnosis and classification of epilepsy. PMID- 27664988 TI - Role of anesthetics in treating status epilepticus: One more piece in the puzzle. PMID- 27664989 TI - Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). AB - OBJECTIVE: To characterize the clinical and MRI features of 2 families with adult onset dominant leukoencephalopathy and strokes and identify the underlying genetic cause. METHODS: We applied MRI pattern recognition, whole-exome sequencing, and neuropathology. RESULTS: Based on brain imaging, 13 family members of 40 years or older from 2 families were diagnosed with the disease; in 11 family members of the same age, MRI was normal. In the affected family members, MRI showed a leukoencephalopathy that was disproportionately severe compared to the clinical disease. The clinical picture was dominated by ischemic and hemorrhagic strokes, slow and late cognitive deterioration, and therapy resistant hypertension. With whole-exome sequencing, we identified one variant shared by both families and segregating with the disease: c.973C>T in CTSA. Haplotype analysis revealed a shared 1,145-kb interval encompassing the CTSA variant on chromosome 20q13.12, suggesting a common ancestor. Brain autopsy of 3 patients showed a leukoencephalopathy that was disproportionately extensive compared to the vascular abnormalities. CTSA encodes cathepsin A. Recessive CTSA mutations cause galactosialidosis. One of the numerous cathepsin A functions is to degrade endothelin-1. In the patients, striking endothelin-1 immunoreactivity was found in white matter astrocytes, correlating with increased numbers of premyelinating oligodendrocyte progenitors. This finding supports a role for endothelin-1 in the leukoencephalopathy through inhibition of oligodendrocyte progenitor maturation. CONCLUSIONS: CARASAL (cathepsin A-related arteriopathy with strokes and leukoencephalopathy) is a novel hereditary adult-onset cerebral small vessel disease. It is of interest that, next to the cerebral vascular abnormalities, endothelin-1 may have a role in the pathogenesis of the extensive leukoencephalopathy. PMID- 27664990 TI - beta-Amyloid Burden Predicts Lower Extremity Performance Decline in Cognitively Unimpaired Older Adults. AB - Background: Motor slowing is associated with risk of Alzheimer's disease. Whether beta-amyloid (Abeta) burden is associated with motor decline, independent of cognitive decline, is unknown. Methods: About 59 cognitively unimpaired older participants had baseline PET-PiB scans and repeated measures of lower (usual gait speed, 400-m time, Health ABC Physical Performance Battery (HABCPPB) score, total standing balance time) and upper (mean tapping time) extremity performance during a mean follow-up of 4.7 years. Linear mixed effect models examined the relationship between baseline Abeta burden and motor decline, adjusting for age, sex, body mass index, cardiovascular risk, APOE E4 status, memory decline, depressive symptoms, ankle-arm index, processing speed, executive function, and cerebrovascular disease. Results: Higher mean cortical Abeta burden was associated with greater declines in gait speed and HABCPPB score and a greater increase in 400-m time. Higher Abeta of putamen was associated with declines in all lower extremity measures, including balance. Higher Abeta of dorsolateral prefrontal cortex and lateral temporal lobe was associated with declines of gait speed and 400-m time, and of precuneus with a greater increase in 400-m time. Associations remained similar after further adjustment. Conclusions: In cognitively unimpaired older adults, Abeta burden overall and in specific brain regions are risk factors for lower extremity motor decline, independent of memory function. These findings provide the first empirical evidence that Abeta burden is a risk factor for mobility decline in older adults. PMID- 27664991 TI - Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs. AB - Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose dependent (MIC 16-32 MUg/ml) or resistant (MIC >= 64 MUg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 MUg/ml. The VT-1129 MIC50 was 0.05 MUg/ml and 0.25 MUg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus. PMID- 27664992 TI - Transcript levels of the Aspergillus fumigatus Cdc42 module, polarisome, and septin genes show little change from dormancy to polarity establishment. AB - Aspergillus fumigatus is the most common airborne pathogen causing fatal mycoses in immunocompromised patients. During the first 8 hours of development A. fumigatus conidia break dormancy, expand isotopically, establish an axis of polarity, and begin to extend germ tubes in a polar manner. The transition from isotropic to polar growth is critical for tissue invasion and pathogenesis. In the current work, we used two-color microarrays to examine the A. fumigatus transcriptome during early development, focusing on the isotropic to polar switch. The most highly regulated transcripts in the isotropic to polar switch did not include known polarity genes. Transcripts encoding the Cdc42 module, polarisome components, and septins, known to be critical players in polarity, showed relatively steady levels during the isotropic to polar switch. Indeed, these transcripts were present in dormant conidia, and their levels changed little from dormancy through germ tube emergence. Not only did the isotropic to polar switch show little change in the expression of key polarity genes of the Cdc42 module, polarisome, and septins, it also showed the lowest overall levels of both up- and downregulation in early development. PMID- 27664993 TI - Type 1 diabetes in children is not a predisposing factor for oral yeast colonization. AB - Type 1 diabetes mellitus (T1D) is considered a risk factor associated with oral yeast infections. The aim of this study was to evaluate the yeast oral carriage (in saliva and mucosal surface) of children with T1D and potential relation with host factors, particularly the subset of CD4+ T cells. Yeasts were quantified and identified in stimulated saliva and in cheek mucosal swabs of 133 diabetic T1D and 72 healthy control subjects. Salivary lymphocytes were quantified using flow cytometry. The presence of yeasts in the oral cavity (60% of total patients) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate or saliva buffer capacity, by age, sex, place of residence, number of daily meals, consumption of sweets or frequency of tooth brushing. Candida albicans was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics. T1D children with HbA1c <= 7.5 (metabolically controlled) presented higher number of CD4+ T salivary subsets when compared with the other groups of children (non-diabetic and nonmetabolically controlled) and also presented the highest number of individuals without oral yeast colonization. In conclusion, T1D does not predisposes for increased oral yeast colonization and a higher number of salivary CD4+T cells seems to result in the absence of oral colonization by yeasts. PMID- 27664994 TI - Prevalence of azole-resistant Aspergillus fumigatus in the environment of Thailand. AB - Occurrence of azole-resistant Aspergillus fumigatus (ARAF) in the environment is an emerging problem worldwide, likely impacting on patient treatment. Several resistance mutations are thought to have initially arisen through triazole-based fungicide use in agriculture and subsequently being propagated in a similar manner. Here we investigated the prevalence of ARAF in the environment of Thailand and characterized their susceptibility profiles toward clinically used azole compounds along with underlying resistance mutations. Three hundred and eight soil samples were collected and analyzed, out of which 3.25% (n = 10) were positive for ARAF. All isolates obtained were resistant to itraconazole (MIC >= 8 MUg/ml), two showed additional increased MIC values toward posaconazole (MIC = 0.5 MUg/ml), and one other toward voriconazole (MIC = 2 MUg/ml). Sequencing of the respective cyp51A genes revealed that eight of the isolates carried the TR34/L98H allele and those two with elevated MIC values to posaconazole the G54R substitution. Although a clear correlation between the use of triazole-based fungicides and isolation of ARAF strains from agricultural lands could not be established for Thailand, but this study clearly demonstrates the spread of globally observed ARAF strains to the environment of South East Asia. PMID- 27664995 TI - Prevalence and Impact of Long-term Use of Nicotine Replacement Therapy in UK Stop Smoking Services: Findings From the ELONS Study. AB - Background: Nicotine replacement therapy (NRT) was licensed for harm reduction in the United Kingdom in 2005, and guidance to UK Stop-Smoking Services (SSS) to include long-term partial or complete substitution of cigarettes with NRT was issued in 2013. Yet, NRT prevalence data and data on changes in biomarkers associated with long-term NRT use among SSS clients are scarce. Methods: SSS clients abstinent 4 weeks postquit date were followed up at 12 months. At baseline standard sociodemographic, smoking and SSS use characteristics were collected and of those eligible, 60.6% (1047/1728) provided data on smoking status and NRT use at follow-up. A subsample also provided saliva samples at baseline and of those eligible, 36.2% (258/712) provided follow-up samples. Saliva was analyzed for cotinine (a metabolite of nicotine) and alpha-amylase (a stress biomarker). Results: Among those who had used NRT during their initial quit attempt (61.5%, 95% CI 58.4%-64.6%), 6.0% (95% CI 4.3%-8.3%) were still using NRT at 1 year, significantly more ex-smokers than relapsed smokers (9.5% vs. 3.7%; p = .005). In adjusted analysis, NRT use interacted with smoking status to determine change in cotinine, but not alpha-amylase, levels (Wald chi2 (1) = 13.0, p < .001): cotinine levels remained unchanged in relapsed smokers and ex smokers with long-term NRT use but decreased in ex-smokers without long-term NRT use. Conclusions: Long-term NRT use is uncommon in SSS clients, particularly among relapsed smokers. Its use is associated with continued high intake of nicotine among ex-smokers but does not increase nicotine intake in smokers. It does not appear to affect stress response. Implications: Little is known about the long-term effects of NRT. Given an increasing shift towards harm reduction in tobacco control, reducing the harm from combustible products by partial or complete substitution with noncombustible products, more data on long-term use are needed. This study shows that in the context of SSS, clients rarely use products for up to a year and that NRT use does not affect users' stress response. Ex-smokers using NRT long-term can completely replace nicotine from cigarettes with nicotine from NRT; long-term NRT use by continuing smokers does not increase nicotine intake. Long-term NRT appears to be a safe and effective way to reduce exposure to combustible nicotine. PMID- 27664996 TI - Reconstruction of Internal and External Exposures of Fukushima Residents. AB - After the Fukushima Daiichi nuclear power plant accident, the internal and external exposures of the residents have been very important issues and concerns. Fukushima prefectural government and Fukushima medical university have been performing the Fukushima Health Management Survey, and the external exposures of the residents have been estimated in the survey by using NIRS external dose estimation system. The doses of 66.3% residents were >1 mSv, and 94.8 % were >2 mSv. For estimating internal exposures of the residents, thyroid measurements, whole body counter measurements and simulation have been applied. These three approach estimations showed that the 90 percentile of thyroid equivalent doses were 10-30 mSv for 1-year-old baby and were 10-20 mSv or less for adults. PMID- 27664997 TI - The First Meeting of the WHO Guideline Development Group for the Revision of the WHO 1999 Guidelines for Iodine Thyroid Blocking. AB - The meeting held in May 2014 in Wurzburg, Germany, discussed the scope of the revision of the 1999 WHO guidelines for iodine thyroid blocking (ITB) by following the WHO handbook for guideline development. This article describes the process and methods of developing the revised, evidence-based WHO guidelines for ITB following nuclear and radiological accidents, the results of the kick-off meeting as well as further steps taken to complete the revision. PMID- 27664998 TI - Capabilities for Clinical Management of Radiation Injuries of the Nikiforov Russian Center of Emergency and Radiation Medicine (EMERCOM of Russia). AB - This article presents an overview of the capabilities for clinical management of radiation injuries available at the Nikiforov Russian Center of Emergency and Radiation Medicine (NRCERM) of the Ministry of the Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters (EMERCOM). NRCERM is a federal state budgetary institution and the Russian Federation's head organization for providing medical assistance for persons overexposed to ionizing radiation, responders to radiation emergencies and people evacuated from radiation contaminated areas. As the WHO Collaborating Center for Treatment and Rehabilitation of Accident Recovery Workers of Nuclear and Other Disasters and a member of the WHO Radiation Emergency Medical Preparedness and Assistance Network (REMPAN), NRCERM is prepared to provide assistance and technical support in case of a radiation accident. For this purpose, NRCERM hospitals are equipped with technologically advanced facilities and possess well trained specialist staff. PMID- 27665000 TI - When opposites lead to the same: a direct comparison of explicit and implicit disgust regulation via fMRI. AB - Cognitive reappraisal and placebo administration constitute two different approaches for modulating one's own emotional state. Whereas reappraisal is an explicit (effortful) type of self-regulation, placebo treatment initiates implicit processes of affective control. The brain mechanisms underlying these processes have not been directly compared with each other up until now; doing this enables the identification of distinct and shared neuronal features. We conducted a functional magnetic resonance imaging study with 45 women, who were presented with disgusting and neutral images in a block design, at three experimental sessions, over 3 consecutive days. They were asked to passively view the images in one session, engage in reappraisal in another, and in another session they received a placebo pill: a disgust-reducing 'anti-nausea drug'. Relative to passive viewing, both reappraisal and placebo treatment effectively reduced the experienced disgust intensity. In the placebo condition, this reduction was associated with decreased activation of the insula and the dorsolateral prefrontal cortex (DLPFC). In contrast, reappraisal induced increased activation in both regions. Furthermore, both regulation strategies were associated with opposite patterns of connectivity in a network encompassing the amygdala, the insula and the DLPFC. Only placebo administration led to a reduced coupling in this network. PMID- 27664999 TI - Oxytocin conditions trait-based rule adherence. AB - Rules, whether in the form of norms, taboos or laws, regulate and coordinate human life. Some rules, however, are arbitrary and adhering to them can be personally costly. Rigidly sticking to such rules can be considered maladaptive. Here, we test whether, at the neurobiological level, (mal)adaptive rule adherence is reduced by oxytocin-a hypothalamic neuropeptide that biases the biobehavioural approach-avoidance system. Participants (N = 139) self-administered oxytocin or placebo intranasally, and reported their need for structure and approach avoidance sensitivity. Next, participants made binary decisions and were given an arbitrary rule that demanded to forgo financial benefits. Under oxytocin, participants violated the rule more often, especially when they had high need for structure and high approach sensitivity. Possibly, oxytocin dampens the need for a highly structured environment and enables individuals to flexibly trade-off internal desires against external restrictions. Implications for the treatment of clinical disorders marked by maladaptive rule adherence are discussed. PMID- 27665001 TI - Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement. AB - Balance between the redox pair of nicotinamide adenine dinucleotides (oxidized NAD+ and reduced NADH), reflects the oxidative state of cells and the ability of biological systems to carry out energy production. A growing body of evidence suggests that an "immuno-oxidative" pathway including oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell-mediated immune response may contribute to disruptions in brain activity in schizophrenia (SZ). The aim of this study is to assess possible redox imbalance in SZ patients by using a novel in vivo 31P MRS technique. The participants included 40 healthy controls, 21 chronic SZ, 13 first-episode (FE) SZ, and 18 FE bipolar disorder (BD) patients (as a psychiatric control group). All participants initially underwent structural imaging at a 3 Tesla (3 T) and 31P MRS measurements were performed on a 4 T MR scanner. NAD+ and NADH components were determined by nonlinear least-square fitting of the model simulated spectra; these incorporated prior chemical shift and coupling constant information to in vivo resonances obtained from 31P MRS experiments. We found a significant reduction in the NAD+/NADH ratio in chronically ill SZ patients compared to a matched healthy control group, and in FE SZ patients compared to both a matched FE BD patient group and a matched healthy control group. These findings provide evidence for redox imbalance in the brain in all phases of SZ, potentially reflecting oxidative stress. PMID- 27665003 TI - The effects of electrical stunning voltage on meat quality, plasma parameters, and protein solubility of broiler breast meat. AB - This study was designed to compare the effects of different stunning voltages of pulsed direct current on meat quality of broilers. For this purpose, plasma parameters, blood loss, carcass damage, and meat water holding capacity, color, shear force, pH, and protein solubility were analyzed. A total of 400 broilers were divided into 5 treatment groups and stunned with 5, 15, 25, 35, and 45 V at 750 Hz and 10 s, respectively. Blood samples were collected immediately after cutting the neck. Pectoralis major muscles were removed from the carcass after chilling and placed on ice. Breast muscle pH and meat color were determined at both 2 and 24 h postmortem. Dripping loss, cooking loss, pressing loss, and cooked breast meat shear values were determined after 24 h postmortem. The 5 V treatment significantly increased (P < 0.05) blood plasma corticosterone and lactate concentration compared with the other groups. The carcass damage of wings, Pectoralis major, and Pectoralis minor was significant in the 5, 35, and 45 V groups. The pH of 2 h postmortem in the 5 and 45 V groups was significantly lower (P < 0.05) than in the 15 and 25 V groups. In the 5 and 45 V groups, the protein solubility and shear force value were significantly lower (P < 0.05) and dripping loss was significantly higher (P < 0.05) than the other groups. PMID- 27665002 TI - Housing First Improves Adherence to Antipsychotic Medication Among Formerly Homeless Adults With Schizophrenia: Results of a Randomized Controlled Trial. AB - Adherence to antipsychotic medication is a significant challenge among homeless patients. No experimental trials have investigated the impact of Housing First on adherence among patients with schizophrenia. We investigated whether Housing First in congregate and scattered-site configurations resulted in superior adherence compared to usual care. Adult participants (n = 165) met criteria for homelessness, schizophrenia, and initiation of antipsychotic pharmacotherapy prior to recruitment to an unblinded, 3-arm randomized controlled trial in Vancouver, Canada. Randomization arms were: congregate Housing First (CHF) with on-site supports (including physician and pharmacy services); scattered-site Housing First (SHF) with Assertive Community Treatment; or treatment as usual (TAU) consisting of existing services. Participants were followed for an average of 2.6 years. Adherence to antipsychotic medication was measured using the medication possession ratio (MPR), and 1-way ANOVA was used to compare outcomes between the 3 conditions. Data were drawn from comprehensive pharmacy records. Prior to randomization, mean MPR among participants was very low (0.44-0.48). Mean MPR in the follow-up period was significantly different between study arms (P < .001) and approached the guideline threshold of 0.80 in SHF. Compared to TAU, antipsychotic adherence was significantly higher in SHF but not in CHF. The results demonstrate that further implementation of SHF is indicated among homeless people with schizophrenia, and that urgent action is needed to address very low levels of antipsychotic adherence in this population (trial registration: ISRCTN57595077). PMID- 27665005 TI - Effects of low-protein diets on growth performance and carcass yield of growing White Pekin ducks. AB - A dose-response experiment with 6 analyzed dietary crude protein (CP) levels (13.54, 14.37, 14.71, 16.04, 16.61, and 17.22%) was conducted to investigate the effects of low-protein diets on growth performance and carcass yield of growing White Pekin ducks from 14 to 35 d of age. All diets were formulated to contain a similar dietary energy level and the standardized ileal digestible amino acid profile including lysine, methionine, threonine, tryptophan, arginine, isoleucine, valine, and glycine. A total of 288 14-day-old male White Pekin ducks were divided into 6 experimental treatments and each treatment contained 8 replicate pens of 6 birds. Ducks were raised in wire-floor pens from 14 to 35 d of age. At 35 d of age, the weight gain, feed intake, feed/gain, and the yield of carcass, breast meat, leg meat, and abdominal fat of ducks from each pen were measured. As dietary CP decreased from 17.22 to 13.54%, weight gain and feed intake were not affected (P > 0.05) but feed/gain increased when dietary CP decreased to 13.54% (P < 0.05). On the other hand, the yield of carcass, leg meat, and breast meat was not influenced by reducing dietary CP (P > 0.05) but the abdominal fat increased when dietary CP was 13.54% (P < 0.05). Based on broken-line regression, the 14.81 and 14.94% were the minimum dietary CP to keep the feed/gain and abdominal fat similar to the ducks fed with 17.22% CP diets, respectively. In summary, with crystalline amino acid supplementation based on a similar standardized ileal digestible amino acid profile, it was possible to formulate the low-protein diets containing about 15% CP for Pekin ducks without adverse effects on their growth performance and carcass yield. PMID- 27665004 TI - Traits of eggshells and shell membranes of translucent eggs. AB - Translucent eggshells negatively affect the appearance of eggs and decrease their economic value. Translocation and accumulation of water from the contents to the shells of eggs are frequent occurrences. Causes of translucent eggshell formation have been investigated, but the primary reason is uncertain. In previous studies, scientists have found that the thickness of the eggshell membrane was significantly different between translucent and opaque eggs. However, there are some conflicts among studies. We performed 2 experiments with 3 breeding flocks of chickens to target the reasons for egg translucence. In experiment 1, eggs of 1,024 Brown-Egg Dwarf Layers (DWL) were used. Approximately 1,600 eggs were collected over 2 consecutive days. They were stored for 3 days, and then 120 translucent and 120 opaque eggs were selected for measurement of egg quality traits and weight loss over several weeks. In experiment 2, we used DWL and White Leghorn pure line (WLL) for assessment of eggshell ultrastructure and membrane traits. We chose 120 translucent and 120 opaque eggs from 3,500 DWL eggs and 125 translucent and 125 opaque eggs from 5,028 WLL eggs. The results are as follows: (1) translucent eggs had greater eggshell strength and lower ultimate failure stress of shell membrane than opaque eggs in both DWL and WLL groups, (2) translucent eggs had thicker shells and thinner shell membranes than opaque eggs in DWL, (3) no significant differences were found in either gas pore or bubble pore traits between translucent and opaque eggs in either line, and (4) no significant differences were detected in internal egg quality or weight loss between translucent and opaque eggs in either line. In summary, the present study suggests that variations in both eggshells and shell membrane structures are implicated in the formation of translucent eggs. PMID- 27665006 TI - Effects of dietary vitamin E type on the growth performance and antioxidant capacity in cyclophosphamide immunosuppressed broilers. AB - Reactive oxygen species and free radicals play multiple roles in some immune pathological events. Vitamin E, as a very potent antioxidant, perhaps deceases the potentially negative effects of such oxidative stress to prevent immune pathological damage to broilers. Therefore, the current study investigated the effects of dietary natural (D-alpha-tocopherol) and synthetic (DL-alpha tocopherol acetate) vitamin E on the growth performance and antioxidant capacity in cyclophosphamide (CY) immunosuppressed broilers. 192 one-day-old male Arbor Acre broilers were randomly distributed into 4 groups: 1) non-CY-challenged control; 2) CY-challenged control; 3) CY-challenged group+20 IU DL-alpha tocopherol acetate per kg feed; and 4) CY-challenged group+20 IU D-alpha tocopherol per kg feed. The maize-soybean basal diet in the control group contained alpha-tocopherol (7.12 mg/kg). Broilers were intramuscularly injected with 80 mg/kg body weight of CY or sterile saline at 16, 17, and 18 d of age. CY decreased (P < 0.05) the average daily gain and average daily feed intake, but vitamin E did not alter the growth performance of broilers before or after CY injection (P > 0.05). The decreased absolute weight of the spleen, thymus and bursa, serum interleukin 2 (IL-2), and interleukin 6 (IL-2) concentrations in CY treated broilers were alleviated by vitamin E (P < 0.05) . The decreased relative weight (g/kg body weight) of the bursa in the CY-treated broilers was increased by natural vitamin E (P < 0.05). The CY-induced increases in malondialdehyde (MDA) content and decreases in total antioxidant capacity (T-AOC), glutathione, vitamin C, and alpha-tocopherol levels, and total superoxide dismutase and glutathione peroxidase activities in both serum and the liver were attenuated by vitamin E (P < 0.05). Additionally, natural vitamin E increased alpha-tocopherol and T-AOC levels and decreased MDA content in the liver of CY-treated broilers (P < 0.05) when compared to the synthetic form. In summary, both synthetic and natural vitamin E supplementation improved lymphoid organ weights, serum IL-2 and IL-6 levels, and antioxidant capacity of immunosuppressed broilers induced by CY. Especially, natural vitamin E was superior to the synthetic form and enhanced alpha-tocopherol and T-AOC levels, reduced MDA concentration in the liver, and alleviated the immune damage of the bursa. PMID- 27665007 TI - Population dynamics and antimicrobial resistance of the most prevalent poultry associated Salmonella serotypes. AB - Salmonella spp. is the most predominant bacterial cause of foodborne gastroenteritis in humans. Due to the risk of human infection associated with poultry products and the prevalence of antimicrobial resistance, Salmonella also poses a significant challenge to commercial poultry production. During the last decade (2002 to 2012), the 12 most prevalent poultry-associated Salmonella serotypes (MPPSTs) were frequently and consistently isolated from poultry products in the United States. These MPPSTs and their percent prevalence in poultry products include Kentucky (4%), Enteritidis (2%) Heidelberg (2%), Typhimurium (2%), S. I 4,[5],12:i:- (0.31%), Montevideo (0.20%), Infantis (0.16%) Schwarzengrund (0.15%), Hadar (0.15%), Mbandaka (0.13%), Thompson (0.12%), and Senftenberg (0.04%). All MPPSTs except Kentucky are among the top 30 clinically significant serotypes that cause human illnesses in the United States. However with the exception of a few widely studied serotypes such as S. Enteritidis and Typhimurium, the ecology and epidemiology of the majority of MPPSTs still remain poorly investigated. Published data from the United States suggests that MPPSTs such as Heidelberg, Typhimurium, Kentucky, and Sentfenberg are more likely to be multi-drug resistant (MDR, >=3 antimicobial classes) whereas Enteritidis, Montevideo, Schwarzengrund, Hadar, Infantis, Thompson, and Mbandaka are generally pan-susceptible or display resistance to fewer antimicobials. In contrast, the majority of MPPSTs isolated globally have been reported to display MDR phenotype. There also appears to be an international spread of a few MDR serotypes including Kentucky, Schwarzengrund, Hadar, Thomson, Sentfenberg, and Enteritidis, which may pose significant challenges to the public health. The current knowledge gaps on the ecology, epidemiology, and antimicrobial resistance of MPPSTs are discussed. PMID- 27665008 TI - Effects of dietary fats on egg quality and lipid parameters in serum and yolks of Shan Partridge Duck. AB - The effects of different dietary fats with variable levels of polyunsaturated fatty acids (PUFAs) on egg quality of Shan Partridge Duck, serum, and yolk lipid parameters were examined in this study. A flock of 585 optimal produced ducks were selected and diets enriched with 0.5%, 1%, or 2% fish oil (F)/flaxseed oil (FL)/rapeseed oil (R)/tallow (T) plus basal diet were supplied through a 28-d period. Supplemental fat source and fat level had no effects on egg qualities. Proportions of yolk total cholesterol (TC), saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) were reduced (P < 0.001), while polyunsaturated fatty acids (PUFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), omega-3 polyunsaturated fatty acids (n-3 PUFAs), Docosahexaenoic Acid (DHA), and Eicosapentaenoic Acid (EPA) were increased by fish oil, flaxseed oil, or rapeseed oil. Effects of supplementation increasing DHA and EPA were detected in F, FL, and R. Compared with C, fish oil significantly increased low-density lipoprotein cholesterol (LDL-C) in serum, flaxseed oil significantly reduced TC and increased very low-density lipoprotein cholesterol (VLDL-C), rapeseed oil significantly reduced TC and LDL-C in serum and increased VLDL-C, tallow significantly increased LDL-C. It is concluded that unsaturated fatty acids rich diets (fish oil, flaxseed oil, and rapeseed oil) might increase yolk PUFAs, reduce yolk cholesterol, and change serum lipid parameters without evident effect on egg qualities. PMID- 27665009 TI - Effects of dietary octacosanol supplementation on laying performance, egg quality, serum hormone levels, and expression of genes related to the reproductive axis in laying hens. AB - This experiment was conducted to evaluate the effects of dietary octacosanol supplementation on laying performance, egg quality, serum hormone levels, and gene expression related to reproductive axis in laying hens to confirm the reproduction-promoting function of octacosanol. In total, 360 Hy-Line Brown (67 wk-old) laying hens were randomly assigned to one of three treatments with 0, 5, and 10 mg octacosanol (extracted from rice bran, purity >92%)/kg feed. The feeding trial lasted for 10 weeks. The results showed that the dietary addition of 5 and 10 mg/kg octacosanol improved feed efficiency by 4.9% and 3.4% (P < 0.01), increased the albumen height by 20.5% and 13.3% (P < 0.01), the Haugh unit score by 12.9% and 8.7% (P < 0.01), and the eggshell strength by 39.5% and 24.5% (P < 0.01), respectively, compared with the control diet. Dietary octacosanol addition significantly affected serum triiodothyronine, estradiol, follicle stimulating hormone levels (P < 0.05), and progesterone and luteinizing hormone level (P < 0.01). Compared with the control, dietary addition of octacosanol at 5 mg/kg promoted the follicle-stimulating hormone receptor (FSHR) mRNA expression in different-sized follicles, and significantly increased the FSHR mRNA expression of granulosa cells from the F2 and F3 follicles (P < 0.05). Dietary supplementation with both 5 and 10 mg/kg octacosanol promoted the mRNA expression of luteinizing hormone receptor and prolactin receptor in different-sized follicles, and significantly up-regulated the expression levels in F1 granulosa cells (P < 0.05). The ovarian weight was significantly increased with the dietary addition of 5 mg/kg octacosanol (P < 0.05). The numbers of small yellow follicles and large white follicles were increased with the addition of dietary 5 and 10 mg/kg octacosanol (P < 0.01). This study provides evidence that octacosanol has the capacity to improve reproductive performance, indicating that it is a potentially effective feed additive in egg production. PMID- 27665010 TI - Sexing chick mRNA: A protocol based on quantitative real-time polymerase chain reaction. AB - The accurate identification of sex in birds is important for research on avian sex determination and differentiation. Polymerase chain reaction (PCR)-based methods have been widely applied for the molecular sexing of birds. However, these methods have used genomic DNA. Here, we present the first sexing protocol for chick mRNA based on real-time quantitative PCR. We demonstrate that this method can accurately determine sex using mRNA from chick gonads and other tissues, such as heart, liver, spleen, lung, and muscle. The strategy of this protocol also may be suitable for other species in which sex is determined by the inheritance of sex chromosomes (ZZ male and ZW female). PMID- 27665011 TI - Evaluation of genetic diversity of Saudi native chicken populations using microsatellite markers. AB - The present study was conducted to evaluate the genetic diversity and relationships of 5 Saudi native chicken populations and a White Leghorn (L) strain as an exotic breed, using 25 microsatellite markers. According to morphological appearance and plumage color and pattern, they were classified into black (BL), black-barred (BR), dark brown (DB), light brown (LB), and gray (G) breeds. Twenty-five microsatellite markers were chosen based on the degree of polymorphism reported in the previous literature. The results revealed that all studied markers exhibited a varied percentage of polymorphism among native chicken populations. However, there were 81 polymorphic loci out of 109 loci. Based on cluster analysis, 3 main clusters of chicken populations were identified. Two clusters comprised native chicken breeds, while the L strain set the third one. Higher similarity was found between either black and gray populations (BL and G) or brown populations (LB and DB). They had a closer relationship to each other. Genetic distance between each couple was 0.11 and 0.12, respectively. The productive results revealed that the black breed had significantly (P < 0.0001) lighter body weight at sexual maturity compared to the other breeds. There was no significant difference between light and dark brown breeds for most productive traits. The genetic diversity we found among Saudi chicken populations may be of interest for improving productive performance and adaptability. PMID- 27665012 TI - Biodetoxification of aflatoxin B1 in cottonseed meal by fermentation of Cellulosimicrobium funkei in duckling diet. AB - Two experiments were conducted to optimize the fermentation of cottonseed meal by Cellulosimicrobium funkei (C. funkei) for the ability of the bacteria to degrade aflatoxin B1 (AFB1) and then to evaluate the bacterial detoxification in ducklings. In experiment 1, the fermentation of cottonseed meal by C. funkei was improved by changing the inoculation amounts by 10% (108 cfu/mL), using a 1:0.5 material to water ratio at 35 degrees C temperature for a 144 h reaction duration, which resulted in an 83.4% biodegradation of AFB1. In experiment 2, 112 one-day-old male Cherry Valley ducklings were randomly allocated to 4 experimental groups with 4 replicates of 7 birds each. For a period of 2 wk the controls received a base duckling diet (BD), a second group received a base diet contaminated with 10% AFB1 cottonseed meal (96.8 MUg AFB1/kg), a third group was fed a base diet added with 5% unfermented and 5% fermented AFB1-contaminated cottonseed meal (57.0 MUg AFB1/kg), and the fourth group was fed a base diet added with 10% AFB1-contaminated fermented cottonseed meal (16.0 MUg AFB1/kg). The growth performance, relative organ weights, and serum biochemistry were analyzed. The results showed that the feed conversion ratio in the second group was lower than that of the controls at wk one and 2 (P < 0.05). Also, after 2 wk, group 2 ducklings had increased relative weights of the liver, kidneys, and spleen, increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), increased concentration of blood urea nitrogen (BUN) and creatinine (Crt), and decreased relative weight of Fabricius bursa (P < 0.05). In addition, the concentrations of total protein (TP) and albumin (ALB) in serum were also significantly higher at weeks one and 2 (P < 0.05). These alterations were attenuated or prevented when 5 or 10% fermented cottonseed meal substituted equal amounts of unfermented cottonseed meal in the diet. In conclusion, fermentation of AFB1-contaminated feed materials by C. funkei offers a new strategy to reduce the negative effects of aflatoxicosis in ducklings. PMID- 27665013 TI - Genetic evaluation of egg production curve in Thai native chickens by random regression and spline models. AB - The objective of this research is to investigate appropriate random regression models with various covariance functions, for the genetic evaluation of test-day egg production. Data included 7,884 monthly egg production records from 657 Thai native chickens (Pradu Hang Dam) that were obtained during the first to sixth generation and were born during 2007 to 2014 at the Research and Development Network Center for Animal Breeding (Native Chickens), Khon Kaen University. Average annual and monthly egg productions were 117 +/- 41 and 10.20 +/- 6.40 eggs, respectively. Nine random regression models were analyzed using the Wilmink function (WM), Koops and Grossman function (KG), Legendre polynomials functions with second, third, and fourth orders (LG2, LG3, LG4), and spline functions with 4, 5, 6, and 8 knots (SP4, SP5, SP6, and SP8). All covariance functions were nested within the same additive genetic and permanent environmental random effects, and the variance components were estimated by Restricted Maximum Likelihood (REML). In model comparisons, mean square error (MSE) and the coefficient of detemination (R2) calculated the goodness of fit; and the correlation between observed and predicted values [Formula: see text] was used to calculate the cross-validated predictive abilities. We found that the covariance functions of SP5, SP6, and SP8 proved appropriate for the genetic evaluation of the egg production curves for Thai native chickens. The estimated heritability of monthly egg production ranged from 0.07 to 0.39, and the highest heritability was found during the first to third months of egg production. In conclusion, the spline functions within monthly egg production can be applied to breeding programs for the improvement of both egg number and persistence of egg production. PMID- 27665014 TI - Nutrients central to maintaining intestinal absorptive efficiency and barrier integrity with fowl. AB - The small intestinal mucosa acts to recover nutrients from the lumen while providing a barrier against potential hazards. Its unstirred water layer (USWL) at the lumen interface involves membrane associated mucin linearly protruding from underlying microvilli that entangles secretory mucin released from local goblet cells. Both mucin sources are dominated by repetitive O-glycosylated areas dependant on threonine, serine, glycine, and proline. Secretory mucin differs from membrane attached mucin by further employing multiple cystines that interconnect these areas into a net-like molecular sieve. All of the glycosylated areas have ionizable acidic groups credited with reducing pH from that in the lumen to create a micro environment favoring enzymes finalizing digestion while optimizing nutrient terms for absorption. Erosion of the USWL and/or abuse of the membrane due to lumen threats require continuous repair. The aforementioned amino acids are necessary in substantial amounts while vitamin B6 collaborates with vitamin A as meaningful cofactors for mucin synthesis. Marginal inadequacies of these nutrients during inordinate demand are expected to impair mucin replacement. In turn, marginal increases in feed conversion likely occur while fostering the probability of necrotic enteritis together with gizzard erosions. Abuse of the absorptive membrane is of particular concern from fatty acid hydroperoxides because of their continual presence in feed and inability of the USWL to provide protection. These hydroperoxides threaten membrane integrity by their inclusion in micelles during digestive events with fat thereby permitting transit through the USWL. Once coalesced with membrane phospholipids, structural aberrations are visualized as interfering with nutrient recovery while enabling leakage of cell contents to potentiate wet excreta. Inclusion of dietary vitamin E along with vitamin A into micelles with fatty acid hydroperoxides provides relief by quenching further peroxidation. Assuring cystine, threonine, glycine, and serine that are directly available as such together with vitamins A, E, and B6 represents one approach toward optimizing maintenance of the intestinal mucosa. PMID- 27665015 TI - Additive effects of fibroblast growth factor 23 neutralization and dietary phytase on chick calcium and phosphorus metabolism. AB - Phytase hydrolyzes phytate rendering phosphorus available for intestinal absorption, while systemic neutralization of fibroblast growth factor 23 (FGF 23), using anti-FGF-23 antibody, has been shown to increase phosphate retention. Hence, neutralization of FGF-23 should be additive with phytase in reducing dietary non-phytate phosphorus (nPP) needs in chickens fed plant-based diets rich in phytic acid. This study was designed to test the additive effects of maternally derived anti-FGF-23 antibody and dietary phytase on the performance of chicks fed a low nPP diet from one to 14 d. Single Comb White Leghorn laying hens were vaccinated with either an adjuvant control or a synthetic FGF-23 peptide (GMNPPPYS). Chicks from vaccinated hens with control or anti-FGF-23 maternal antibodies were fed either a diet containing 0.2% nPP and 0.9% calcium with or without 500 unit phytase per kg of diet (2 * 2 factorial with main effects of antibody type and phytase addition, n = 15 pens of chicks/treatment). A significant interaction between dietary phytase and maternally derived anti-FGF 23 antibody on growth and feed efficiency was observed (P <= 0.05), in which chicks receiving either phytase or maternally derived anti-FGF-23 antibody had improved body weight gain (21 or 15%, respectively) and feed efficiency (16 or 18%, respectively) as compared to chicks with control antibody and not fed phytase. Both phytase and maternally derived anti-FGF-23 antibody independently increased (P <= 0.05) plasma phosphate (11 and 11%, respectively) and percent tibiotarsus ash (13 and 11%, respectively). Significant main effects and the lack of an interaction supported an additive effect of phytase and anti-FGF-23 antibody on plasma phosphate and percent tibiotarsus ash. Feeding phytase to chicks fed 0.2% nPP increased plasma FGF-23 levels by 22% (P <= 0.05); however, no effects of anti-FGF-23 antibody on plasma FGF-23 levels were observed. In conclusion, dietary phytase and presence of anti-FGF-23 antibody have an additive effect on plasma phosphate and tibiotarsus ash in chicks fed low nPP diets. Data support that phytase and anti-FGF-23 antibody increase phosphate utilization by different mechanisms. PMID- 27665016 TI - Effect of white striping myopathy on breast muscle (Pectoralis major) protein turnover and gene expression in broilers. AB - WS: A study was conducted to evaluate the effect of white striping ( ) of broiler breast muscle ( Pectoralis major ) on protein turnover and gene expression of genes related to protein degradation and fatty acid synthesis. A total of 560 day old male broiler chicks Cobb 500 were allocated in a total of 16 pens, 35 chicks per pen. A completely randomized design was conducted with a 2 * 3 factorial arrangement (2 scores: severe and normal, and 3 breast meat samples sites). At d 60, 20 birds were randomly selected, euthanized, and scored for white striping. Scoring was either normal ( , no WS) or severe ( ). Also, the same day, 17 birds (16 infused, one control) were randomly selected and infused with a solution of 15 N Phen 40% ( ). Breast muscle tissue was taken for gene expression analysis of the following genes: MuRF1, atrogin-1, IGF-1, insulin receptor ( ), fatty acid synthetase, and acetyl CoA carboxylase ( ). Each bird was humanely euthanized after 10 minutes of infusion and scored for WS (NORM or SEV). Samples of the breast muscle ( Pectoralis major ) were taken at different layers (3 samples per bird: ventral, medial, dorsal), along with a sample of excreta for 3 methylhistidine analysis. Out of the 16 breast samples taken, only 10 were selected for analysis based on the WS score (5 NORM and 5 SEV). No significant differences ( P > 0.05) were found in fractional synthesis rate ( ) between SEV WS, NORM and sample sites for breast meat. However, fractional breakdown rate ( ) was significantly higher in birds with SEV WS compared to NORM (8.2 and 4.28, respectively, P < 0.0001). Birds with SEV WS showed significantly higher ( P < 0.05) relative expression of MuRF1 and slightly higher ( P = 0.07) relative expression of atrogin-1 than the NORM birds. These birds also showed lower ( P < 0.05) relative expression of IGF-1 than NORM birds. Further studies are needed to better understand why birds with severe white striping are degrading more muscular protein and mobilizing more fat. PMID- 27665017 TI - Lipid oxidation and color changes of goose meat stored under vacuum and modified atmosphere conditions. AB - The objective of the work was to investigate the color and lipid oxidation changes of goose breast meat packaged in vacuum and modified atmosphere (MA) conditions consisting of 80% O2, 20% CO2, and stored in refrigerated conditions at 4 degrees C. Color stability was monitored by determining total heme pigments concentration; relative concentration of myoglobin, oxymyoglobin, and metmyoglobin; parameters of color L*, a*, b*, and sensory evaluation of the surface color. Lipid stability was measured by determining thiobarbituric acid reactive substances (TBARS). The samples were examined in 24 h after slaughter (unpacked muscles) and on d 4, 7, 9, 11 of storage (muscles packed in vacuum and in MA). Through the time of storage, samples packed in MA had higher TBARS values in comparison to the meat packed in vacuum. For samples packed in two types of atmospheres, the total pigments concentration decreased gradually within 11 d of storage. It was observed that relative metmyoglobin concentration increased whereas relative oxymyoglobin concentration decreased in total heme pigments in the MA stored muscle. The relative concentration of all three myoglobin forms sample packed in vacuum remained unchanged. The color parameters (L*, a*, b*) did not change for 11 d of storage for the vacuum packed meat. The value of the color parameter a* decreased and the value of the color parameters L* and b* increased in the samples packaged in MA. The data prove that if you store goose meat in MA (consisting of 80% O2, 20% CO2) or vacuum, the unchanged surface color is preserved for 9 and 11 day, respectively.Vacuum appears to be a better method as regards the maintaining of lipid stability in goose meat. PMID- 27665018 TI - Application of loop-mediated isothermal amplification with propidium monoazide treatment to detect live Salmonella in chicken carcasses. AB - Raw chicken products are major causes of human foodborne salmonellosis worldwide. In particular, there is a significant risk of human exposure to Salmonella originating from the chicken slaughtering process. Controlling the contamination of chicken carcasses by Salmonella has been a considerable challenge in chicken slaughtering facilities and involves routine microbiological monitoring using reliable detection methods. Simple and rapid detection methods, particularly those capable of determining cell viability, will significantly facilitate routine monitoring of Salmonella Here, we report an invA-based loop-mediated isothermal amplification method coupled with a simple propidium monoazide treatment (PMA-LAMP) for simple and rapid detection and quantification of viable Salmonella in rinse water of chicken carcasses. In this study, PMA-LAMP consistently gave negative results for isopropanol-killed Salmonella with concentrations up to 8.0 * 106 CFU/reaction. The detection limit of PMA-LAMP was 8.0 * 101 CFU/reaction with viable Salmonella in both pure culture and rinse water of chicken carcasses, and 10-fold lower than a conventional polymerase chain reaction coupled with PMA (PMA-PCR) targeting invA There was a high correlation (R2 = 0.99 to 0.976) between LAMP time threshold (TT) values and viable Salmonella with a quantification range of 1.0 * 103 to 1.0 * 108 CFU/mL in pure culture and rinse water of chicken carcasses. The PMA-LAMP assay took less than 2 h to detect Salmonella contaminated in test samples. Therefore, this simple and rapid method will be a very useful tool to detect live Salmonella contamination of chicken carcasses without pre-enrichment at the slaughterhouse where sanitizing treatments are commonly used. PMID- 27665019 TI - Cross-sectional association between muscle strength and self-reported physical function in 195 hip osteoarthritis patients. AB - INTRODUCTION: This study aimed to evaluate associations between strength of selected hip and knee muscles and self-reported physical function, and their clinical relevance, in men and women with hip osteoarthritis (OA). METHODS: Cross sectional data from 195 participants with symptomatic hip OA were used. Peak isometric torque of hip extensors, flexors, and abductors, and knee extensors were measured, along with physical function using the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Separate linear regressions in men and women were used to determine the association between strength and physical function accounting for age, pain, and radiographic disease severity. Subsequently, magnitudes of strength associated with estimates of minimal clinically important improvement (MCII) in physical function were estimated according to severity of difficulty with physical function. RESULTS: For men, greater strength of the hip extensors, hip flexors and knee extensors were each associated with better physical function. For women, greater muscle strength of all tested muscles were each associated with better physical function. For men and women, increases in muscle strength between 17-32%, 133 223%, and 151-284% may be associated with estimates of MCII in physical function for those with mild, moderate, and severe physical dysfunction, respectively. CONCLUSION: Greater isometric strength of specific hip and thigh muscle groups may be associated with better self-reported physical function in men and women. In people with mild physical dysfunction, an estimate of MCII in physical function may be associated with attainable increases in strength. However, in patients with more severe dysfunction, greater and perhaps unattainable strength increases may be associated with an estimate of MCII in physical function. Longitudinal studies are required to validate these observations. PMID- 27665020 TI - The Conundrum of Heterogeneities in Life History Studies. AB - What causes interindividual variation in fitness? Evidence of heritability of latent individual fitness traits has resparked a debate about the causes of variation in life histories in populations: neutralism versus empirical adaptationism. This debate about the processes underlying observed variation pits neutral stochastic demographic processes against evolutionarily relevant differences among individual fitness traits. Advancing this debate requires careful consideration of differences among inference approaches used by proponents of each hypothesis. Here we draw parallels between several disciplines focusing on processes generating variation in individuals' life-course, and we contrast methodologies to disentangle these processes. We draw on other disciplines to clarify terminology, risks of flawed inference, and expand the panel of hypotheses and formalizations of processes generating variation in life histories. PMID- 27665022 TI - Overproduction of nitric oxide intensifies brain infarction and cerebrovascular damage through reduction of claudin-5 and ZO-1 expression in striatum of ischemic brain. AB - Nitric oxide (NO) overproduction has been demonstrated from different NO-synthase overexpression or hyperactivity after brain ischemia. Here, we examined the effects of inhibition of NO overproduction on brain infarction, cerebrovascular damage and expression of claudin-5 and zonula occludens-1 (ZO-1) in striatum of ischemic brain. The experiment was performed in three groups of rats; sham, control ischemia and ischemic treatment. Brain ischemia was induced by 60min of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Treated rats received L-NAME 30min before induction of ischemia (1mg/kg, i.p.). Infarct volume and histopathological changes of ischemic striatum were assessed by TTC and LFB staining methods, respectively. Ultimately, quantitative RT-PCR was used for assessment of claudins-5 and ZO-1 expression. MCAO in the control group induced infarction (135+/-25mm3) at large areas of striatum in accompany with neuronal damages, whereas L-NAME significantly reduced infarction (87+/-16mm3) and neuronal injuries. The mRNA of ZO-1 and claudin-5 decreased in ischemic striatum, whereas inhibition of NO overproduction by L-NAME attenuated this reduction for these genes. Our findings indicated that NO overproduction after brain ischemia plays a crucial role in neuronal damage especially at striatal regions. Hence, inhibition of excessive NO production may save striatal cerebrovascular integrity of ischemic brain. PMID- 27665023 TI - Natural killer cells in malignant hematology: A primer for the non-immunologist. AB - Natural killer cells were first described over 40years ago, but the last 15years has shown tremendous progress in our understanding of their biology and our ability to manipulate them for clinical therapeutic effect. Despite the increased understanding by clinicians and scientists investigating these cells, their biology remains a confusing subject for many because of the wide array of receptors, complex interactions, multiple models of predicting function, and contradictory data in the literature. While they are microscopically indistinguishable from T cells and share many of the same effector functions, their mechanisms of target recognition are completely distinct from yet complimentary to T cells. In this review we provide a basic understanding of NK cell biology and HLA recognition as compared and contrasted to T cells using a metaphor of border patrol and passports. We conclude with a summary of the evidence for NK cell effects in hematologic malignancies and describe new advances in NK cell immunotherapy aimed at improving these effects. PMID- 27665021 TI - A Rare Case of S310F Somatic ERBB2 Mutation in a HER2-Nonamplified Breast Cancer. PMID- 27665024 TI - BCR-ABL (Ph)-like acute leukemia-Pathogenesis, diagnosis and therapeutic options. AB - Recent comprehensive genetic studies revealed numerous genetic aberrations underlying a group of high-risk leukemias that share a specific activated kinase gene expression pattern. These ALLs were first recognized by the expression profile similar to that of Philadelphia chromosome-positive ALL and currently can be sub-classified by the main aberrantly activated kinase in the leukemic cells. We herein review the biological mechanisms and diagnostic and clinical challenges presented by these leukemias. PMID- 27665025 TI - Hoarding disorder and the legal system: A comparative analysis of South African and Dutch law. AB - Hoarding is an internationally recognised disability. Those who suffer from hoarding behaviour can be comfortably brought within the definition of disability found in the Convention on the Rights of Persons with Disabilities and should be provided with "reasonable accommodation" where doing so does not place an unjustified burden on others. However, hoarding also poses a threat to public health, and hoarders' behaviour may infringe on the rights of their neighbours and landlords. Thus, through their behaviour, hoarders may ultimately come into conflict with various areas of law, including neighbour law, housing law as well as administrative law. This article examines how hoarding may be addressed by the law in both South Africa and the Netherlands. It seeks to answer to what extent hoarders are provided with "reasonable accommodation" when their behaviour brings them into conflict of the law in these two jurisdictions. It also takes cognisance of the need to balance the provision of "reasonable accommodation" with the rights of neighbours and landlords. Finally, it seeks to assess which of the two jurisdictions provides the most balanced approach to handling hoarding, in light of the need for therapeutic jurisprudence. PMID- 27665026 TI - Reliability and validity of the DSM-IV-TR and proposed DSM-5 criteria for pedophilia: Implications for the ICD-11 and the next DSM. AB - We tested the inter-rater reliability and criterion-related validity of the DSM IV-TR pedophilia diagnosis and proposed DSM-5 pedohebephilia diagnosis in a sample of 79 men who had committed child pornography offenses, contact sexual offenses against children, or who were referred because of concerns about whether they had a sexual interest in children. Participants were evaluated by two independent psychiatrists with an interview and questionnaire regarding demographic characteristics, sexual history, and self-reported sexual interests; they also completed phallometric and visual reaction time testing. Kappa was .59 for ever meeting DSM-IV-TR criteria for pedophilia and .52 for ever meeting the proposed DSM-5 criteria for pedohebephilia. Ever meeting DSM-IV-TR diagnosis was significantly related to self-reported index of sexual interest in children (highest AUC=.81, 95% CI=.70-.91, p<.001) and to indices of sexual interest in children from phallometric testing (AUC=.70; 95% CI=.52-.89; p<.05) or a computerized assessment based on visual reaction time and self-report (AUC=.75; 95% CI=.62-.88; p<.005). Ever meeting the proposed DSM-5 "diagnosis" was similarly related to self-report (AUC=.84, 95% CI=.74-.94, p<.001) and to the two objective indices, with AUCs of .69 (95% CI=.53-.85; p<.05) and .77 (95% CI=.64 .89; p<.001), respectively. Because the pDSM-5 criteria did not produce significantly better reliability or validity results and users are more familiar with the current DSM-5 criteria, we believe these results suggest the revision of DSM-5 and development of ICD-11 could benefit from drawing on the current DSM-5 criteria, which are essentially the same as DSM-IV-TR except for a distinction between having a paraphilia (the interest) and a paraphilic disorder (the paraphilia plus clinically significant distress or impairment). PMID- 27665027 TI - Size, density and cholesterol load of HDL predict microangiopathy, coronary artery disease and beta-cell function in men with T2DM. AB - The role of high-density lipoprotein cholesterol (HDL-C) as modifiable risk factor for cardiovascular (CV) disease is increasingly debated, notwithstanding the finding that small-dense and dysfunctional HDL are associated with the metabolic syndrome and T2DM. In order to better clarify the epidemiological risk related to HDL of different size/density, without resorting to direct measures, it would seem appropriate to adjust HDL-C to the level of its main apolipoprotein (apoA-I), thereby providing an [HDL-C/apoA-I] ratio. The latter allows not only to estimate an average size for HDLs, but also to derive indices on particle number, cholesterol load, and density. So far, the potential usefulness of this ratio in diabetes is barely addressed. To this end, we sorted 488 male patients with T2DM according to [HDL-C/apoA-I] quartiles (Q), to determine how the ratio relates to cardiometabolic risk, beta-cell function, glycaemic control, and micro and macrovascular complications. Five lipid parameters were derived from the combined determination of HDL-C and apoA-I, namely HDL size; particle number; cholesterol load/particle; apoA-I/particle; and particle density. An unfavorable cardiometabolic profile characterized patients from QI and QII, in which HDLs were pro-atherogenic, denser and apoA-I-depleted. By contrast, QIII patients had an [HDL-C/apoA-I] ratio close to that of non-diabetic controls. QIV patients had better than average HDL size and composition, and in those patients whose [HDL C/apoA-I] ratio was above normal, a more favorable phenotype was observed regarding lifestyle, anthropometry, metabolic comorbidities, insulin sensitivity, MetS score/severity, glycaemic control, and target-organ damage pregalence in small or large vessels. In conclusion, [HDL-C/apoA-I] and the resulting indices of HDL composition and functionality predict macrovascular risk and beta-cell function decline, as well as overall microangiopathic risk, suggesting that this ratio could serve both in cardiometabolic assessment and as biomarker of vascular complications. PMID- 27665028 TI - Muscle development in healthy children evaluated by bioelectrical impedance analysis. AB - OBJECTIVES: This study aimed to use bioelectrical impedance analysis (BIA) to generate a new muscle density index (MDI), the MDI_BIA, to evaluate muscle development, and to demonstrate the changes that occur in the BIA-based muscle cross-sectional area index (MCAI_BIA) that accompany growth. We also sought to determine the traceability of chronological changes in the MDI_BIA and MCAI_BIA. METHODS: Healthy children (n=112) aged 8.68+/-3.16years (0.33-14.00years) underwent bioelectrical impedance (BI) measurements of their upper arms, thighs, and lower legs. The MDI_BIA and MCAI_BIA were calculated, and cross-sectional investigations were conducted into the changes in these indices that accompanied growth. Data collected after 1.10+/-0.08years from 45 participants determined the traceability of the chronological changes in the MDI_BIA and MCAI_BIA. RESULTS: The MDI_BIA and MCAI_BIA were significantly positively correlated with age and height at all locations (P<0.01). The relationships between the locations and the MDI_BIA and MCAI_BIA differed, indicating that these indices evaluated the muscles from different perspectives. Except for the upper arm MDI_BIA, both indices at all locations regardless of age, showed significant chronological increases after an average period of 1.10years. CONCLUSIONS: The MDI_BIA and MCAI_BIA were significantly correlated with age and height in healthy children, and they showed significant chronological increases. Hence, these indices could be used to represent muscle development and muscle mass increases. BIA is non invasive, convenient, and economical and it may be useful in evaluating muscle development and muscle cross-sectional areas in children. PMID- 27665029 TI - Seasonal influenza vaccination among Chinese health care workers. AB - We conducted a study to examine the knowledge, attitudes, and opinions of health care workers (HCWs) and the factors associated with receipt of influenza vaccination in HCWs during August 2015 in 3 hospitals in Jiangsu Province, China. Among the 173 doctors and 220 nurses included in this study, the proportions who received vaccination for the 2014-2015 season were 14% and 13%, respectively. Ninety-eight percent of doctors and 99% of nurses maintained their vaccination practice over 4 seasons. PMID- 27665030 TI - Utility of electronic hand hygiene counting devices for measuring physicians' hand hygiene adherence applied to outpatient settings. AB - BACKGROUND: Our objectives were to evaluate the utility of electronic hand hygiene counting devices in outpatient settings and the impact of results feedback on physicians' hand hygiene behaviors. METHODS: We installed 130 electronic hand hygiene counting devices in our redesigned outpatient department. We remotely monitored physicians' hand hygiene practices during outpatient examinations and calculated the adherence rate as follows: number of hand hygiene counts divided by the number of outpatients examined multiplied by 100. Physician individual adherence rates were also classified into 4 categories. RESULTS: Two hundred and eighty physicians from 28 clinical departments were monitored for 3 months. The overall hand hygiene adherence rate was 10.7% at baseline, which improved significantly after feedback to 18.2% in the third month. Of the clinical departments, 78.6% demonstrated significant improvement in hand hygiene compliance. The change in the percentage of physicians in each category before and after feedback were as follows: very low (84.3% to 72.1%), low (8.6% to 14.3%), moderate (2.9% to 8.9%), and high (4.3% to 4.6%), from the first to third month, respectively. Based on category assessment, 17.1% of physicians were classified as responders. CONCLUSIONS: Physicians' adherence to hand hygiene practices during outpatient examinations was successfully monitored remotely using electronic counting devices. Audit and feedback of adherence data may have a positive impact on physicians' hand hygiene compliance. PMID- 27665031 TI - Impact and feasibility of an emergency department-based ventilator-associated pneumonia bundle for patients intubated in an academic emergency department. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) has been linked to emergency department (ED) intubation and length of stay (LOS). We assessed VAP prevalence in ED intubated patients, feasibility of ED VAP prevention, and effect on VAP rates. METHODS: This was a quality improvement initiative using a pre/post design. Phase 1 (PRE1) comprised patients before intensive care unit (ICU) bundle deployment. Phase 2 (PRE2) occurred after ICU but before ED deployment. Phase 3 (POST) included patients received VAP prevention starting at ED intubation. Log rank test for equality and Cox regression using a Breslow method for ties were performed. Bundle compliance was reported as percentages. Number needed to treat (NNT) was calculated by ventilator day. RESULTS: PRE1, PRE2, and POST groups were composed of 195, 192, and 153 patients, respectively, with VAP rates of 22 (11.3%), 11 (5.7%), and 6 (3.9%). Log-rank test showed significant reduction in VAP (chi2 = 9.16, P = .0103). The Cox regression hazard ratio was 1.38 for the Clinical Pulmonary Infection Score (P = .001), and the hazard ratio was 0.26 for the VAP bundle (P = .005). Bundle compliance >50% for head-of-bed elevation, oral care, subglottic suctioning, and titrated sedation improved significantly with introduction of a registered nurse champion. NNT varied from 7 to 11. CONCLUSIONS: VAP was common for ED intubated patients. ED-based VAP prevention is feasible. We demonstrate significant reduction in VAP rates, which should be replicated in a multicenter study. PMID- 27665032 TI - Characteristics of national and statewide health care-associated infection surveillance programs: A qualitative study. AB - BACKGROUND: There are many well-established national health care-associated infection surveillance programs (HAISPs). Although validation studies have described data quality, there is little research describing important characteristics of large HAISPs. The aim of this study was to broaden our understanding and identify key characteristics of large HAISPs. METHODS: Semi structured interviews were conducted with purposively selected leaders from national and state-based HAISPs. Interview data were analyzed following an interpretive description process. RESULTS: Seven semi-structured interviews were conducted over a 6-month period during 2014-2015. Analysis of the data generated 5 distinct characteristics of large HAISPs: (1) triggers: surveillance was initiated by government or a cooperative of like-minded people, (2) purpose: a clear purpose is needed and determines other surveillance mechanisms, (3) data measures: consistency is more important than accuracy, (4) processes: a balance exists between the volume of data collected and resources, and (5) implementation and maintenance: a central coordinating body is crucial for uniformity and support. CONCLUSIONS: National HAISPs are complex and affect a broad range of stakeholders. Although the overall goal of health care-associated infection surveillance is to reduce the incidence of health care-associated infection, there are many crucial factors to be considered in attaining this goal. The findings from this study will assist the development of new HAISPs and could be used as an adjunct to evaluate existing programs. PMID- 27665033 TI - A parainfluenza virus type 3 outbreak at a residential aged care facility: The role of microbiologic testing in early identification and antimicrobial stewardship. AB - We report an outbreak of parainfluenza 3, which had an attack rate of 30%, in a residential care facility in Melbourne, Australia. One-fifth of affected residents required hospitalization, but there were no deaths. The outbreak demonstrated the value of active surveillance and early microbiologic testing and the urgent need for antimicrobial stewardship programs in the aged care setting. PMID- 27665034 TI - Epidemiology and economic impact of health care-associated infections and cost effectiveness of infection control measures at a Thai university hospital. AB - BACKGROUND: Data on clinical and economic impact of health care-associated infections (HAIs) from resource limited countries are limited. We aimed to determine epidemiology and economic impact of HAIs and cost-effectiveness of infection prevention and control measures in a resource-limited setting. METHODS: A retrospective cohort study was conducted among hospitalized patients at Siriraj Hospital, Thailand. Results from the cohort were subsequently used to conduct cost-effective analysis (CEA) to compare the comprehensive implementation of individualized bundling infection control measures (IBICMs) with regular infection control care. RESULTS: From February-May 2013, there were 515 hospitalizations (497 patients) with 7,848 hospitalization days. Cumulative incidence of HAIs was 23.30%, and the incidence rate of HAIs was 18.66 +/- 44.19 per 1,000 hospitalization days. Hospital mortality among those with and without HAIs was 33.33% and 20.00%, respectively (P < .001). The adjusted cost attributable to HAIs was $704.72 +/- $226.73 (P < .001). CEA identified IBICMs as a non-dominated strategy, with an incremental cost-effectiveness ratio of $20,444.62 per life saved. CONCLUSIONS: HAI is significantly related with higher hospital mortality, longer length of stay, and higher hospitalization costs. IBICMs were confirmed to be cost-effective at Siriraj Hospital. Implementing this intervention could improve care quality and save costs. PMID- 27665035 TI - Could we predict airborne Aspergillus contamination during construction work? AB - BACKGROUND: Aspergillus fumigatus is a major opportunistic pathogen causing nosocomial infection. Hospital outbreaks of invasive aspergillosis have been associated with demolition and building construction. This study was designed to examine the impact of meteorologic factors and different periods of work on outdoor fungal airborne concentrations. METHODS: The study was conducted at Necker Enfants Malades Hospital, a 650-bed teaching care hospital recently involved in a large construction program, including renovation, construction, and demolition. During the work phases, prospective external air samplings were performed 3 times a week, and meteorologic parameters were collected every day. RESULTS: Two hundred and one samples were collected. Aspergillus spp were found in 80.1% of samples, with a median concentration of 16 colony forming units (CFU)/m3. A significant increase in the colony count of molds occurred after demolition. In the multivariate analysis, factors associated with overall fungi concentration were the type of work construction and temperature. Elevated Aspergillus spp concentrations (>20 CFU/m3) were associated with higher temperature. CONCLUSIONS: Our findings underline the importance of environmental surveillance. According to our results we suggest that demolition work should be performed during the winter and fall seasons. PMID- 27665036 TI - Dazed and Confused: Medical Cannabis in Alzheimer Disease. PMID- 27665037 TI - Paediatrician perceptions of patient referral and discharge. AB - Objective The aim of the present study was to determine the factors involved in the decision of paediatric specialists to discharge patients back to their primary care provider following referral. Return of patients to primary care, when medically appropriate, is essential to provide efficient care to children given the limited workforce of paediatric subspecialists in Australia. Methods Data were compiled from a self-completed mail survey of all paediatricians in five specialties at two children's hospitals in Melbourne (n=81). Analysis involved frequency distributions and descriptive analyses, followed by bivariate analyses to determine the differences, if any, among respondents based on the demographic variables collected. Results The response rate was 91%. Most paediatricians (73%) believed that at least sometimes referrals were for a condition general practitioners (GPs) should be able to manage themselves. However, only 36% reported that they frequently or almost always provided the referring GP with information on how to care for the particular condition without a referral. Concerns regarding whether a patient would receive required care following discharge were felt to be important by most paediatricians. Further, many paediatricians reported that their discharge decision is affected by concerns it would be too complicated to arrange for a GP to take over the care of a patient. Conclusions Understanding the factors involved in the referral process and the decision to discharge patients from speciality care clinics to primary care is essential to develop strategies to address long waiting times. Ensuring appropriate referral of children involves the participation of GPs, parents and specialists. What is known about the topic? Most paediatric subspecialists practice in paediatric hospitals, where there is a sufficient volume of patients requiring their services. There have been reports across Australia of increased referrals to general and subspecialist paediatricians, with subsequent increases in waiting times and difficulties accessing timely care for children. There are anecdotal reports of inappropriate referrals to paediatric subspecialty clinics. What does this paper add? There is broad sentiment among paediatric specialists that they receive many referrals from GPs without either a clear rationale for the referral and/or sufficient information regarding the clinical history of the patient. Few paediatricians report contacting the referring GP to obtain additional information. Paediatricians believe parents are a frequent driver of both necessary and unnecessary referrals. What are the implications for practitioners? Understanding the factors involved in the referral process and the decision to discharge patients from speciality care clinics to primary care is essential to develop strategies to address long waiting times. PMID- 27665039 TI - Parental Decision-Making Preferences in Neonatal Intensive Care. AB - OBJECTIVE: To explore how characteristics of medical decisions influence parents' preferences for control over decisions for their seriously ill infants. STUDY DESIGN: In qualitative interviews, parents of infants in the neonatal intensive care unit (NICU) were asked to consider all medical decisions they could recall, and were prompted with decisions commonly encountered in the NICU. For each decision, parents were asked detailed questions about who made each decision, whom they would have preferred to make the decision, and why. Using standard qualitative methods, responses were coded and organized such that decision-level characteristics could be analyzed according to preferred decision-making role. RESULTS: Parents identified 2 factors that were associated with a preference to delegate decisions to the medical team (high degree of urgency, high level of required medical expertise) and 4 factors associated with a preference to retain parental control (high perceived risk, high personal experience with the decision, involvement of foreign bodily fluids, and similarity to decisions that they perceived as part of the normal parental role). CONCLUSIONS: Characteristics of decisions influence preferences for control over medical decisions among parents of patients in the NICU. These insights may guide improvements in physician-parent communication and consent. PMID- 27665038 TI - Body fat distribution in Parkinson's disease: An MRI-based body fat quantification study. AB - INTRODUCTION: There is some evidence that Parkinson's Disease (PD) patients have lower body weight and lower fat mass when compared to healthy subjects and that lower body weight and fat mass influence disease risk and progression. It remains unclear, however, if weight loss of fat mass loss occurs only in a subgroup of patients and whether fat distribution is altered during PD. The aim of this study was to prospectively investigate adipose tissue content and distribution in PD patients. METHODS: The body fat composition of PD patients (N = 54) was compared with age matched healthy controls (N = 55) using a magnetic resonance imaging (MRI)-based method. A longitudinal MRI scan was acquired in 25 PD patients after a mean follow up period of 12 months. RESULTS: The volume of total body fat as well as of visceral fat showed no difference between PD patients and healthy controls at baseline or at follow up. However, PD patients displayed decreased subcutaneous fat tissue (p = 0.01) and a higher visceral to subcutaneous fat ratio as compared to controls (p = 0.004). After follow up, 16 PD patients did not lose weight, while 9 PD patients lost between 0.5 and 10 kg. CONCLUSION: Fat distribution is altered in PD patients, with an increased ratio of visceral to subcutaneous fat. PMID- 27665040 TI - Risk of Ventricular Arrhythmias and Association with Ondansetron. AB - OBJECTIVES: To evaluate the use of ondansetron in a tertiary care pediatric health system, assess the incidence of ventricular tachyarrhythmia within 24 hours of ondansetron, and identify the characteristics of children experiencing a ventricular tachyarrhythmia after ondansetron, to identify potential risk factors. STUDY DESIGN: This retrospective chart review identified children <=18 years of age who received ondansetron within 24 hours prior to a ventricular tachyarrhythmia. Those identified were evaluated for other diagnoses, concomitant medication use, electrolyte abnormalities, or underlying conduction abnormalities that may have contributed to the arrhythmia. RESULTS: A total of 199 773 doses of ondansetron were administered to 37 794 patients over 58 009 visits. Average dose was 0.13 mg/kg/dose (range 0.005-0.86 mg/kg/dose). Seven patients received ondansetron within 24 hours prior to a ventricular arrhythmia. All 7 patients had underlying congenital cardiac conduction abnormalities (n = 3) or other major cardiac diagnoses (n = 4). In clinical review, torsades de pointes was found in only 1 of the 7 patients. CONCLUSIONS: This retrospective study found the risk of ventricular arrhythmia within 24 hours after ondansetron administration was 3 in 100 000 patients treated annually (0.003%). Children with major cardiac conditions could be considered for electrocardiogram screening and continuous cardiac monitoring while receiving ondansetron. Our findings do not support recommendations for electrocardiogram screening or continuous monitoring of other pediatric populations receiving ondansetron. PMID- 27665041 TI - Hospitalization Cost Model of Pediatric Surgical Treatment of Chiari Type 1 Malformation. AB - OBJECTIVES: To develop a cost model for hospitalization costs of surgery among children with Chiari malformation type 1 (CM-1) and to examine risk factors for increased costs. STUDY DESIGN: Data were extracted from the US National Healthcare Cost and Utilization Project 2009 Kids' Inpatient Database. The study cohort was comprised of patients aged 0-20 years who underwent CM-1 surgery. Patient charges were converted to costs by cost-to-charge ratios. Simple and multivariable generalized linear models were used to construct cost models and to determine factors associated with increased hospital costs of CM-1 surgery. RESULTS: A total of 1075 patients were included. Median age was 11 years (IQR 5 16 years). Payers included public (32.9%) and private (61.5%) insurers. Median wage-adjusted cost and length-of-stay for CM-1 surgery were US $13 598 (IQR $10 475-$18 266) and 3 days (IQR 3-4 days). Higher costs were found at freestanding children's hospitals: average incremental-increased cost (AIIC) was US $5155 (95% CI $2067-$8749). Factors most associated with increased hospitalization costs were patients with device-dependent complex chronic conditions (AIIC $20 617, 95% CI $13 721-$29 026) and medical complications (AIIC $13 632, 95% CI $7163-$21 845). Neurologic and neuromuscular, metabolic, gastrointestinal, and other congenital genetic defect complex chronic conditions were also associated with higher hospital costs. CONCLUSIONS: This study examined cost drivers for surgery for CM-1; the results may serve as a starting point in informing the development of financial risk models, such as bundled payments or prospective payment systems for these procedures. Beyond financial implications, the study identified specific risk factors associated with increased costs. PMID- 27665042 TI - High-Grade Myxoid Liposarcoma (Round Cell Variant) in a Dog. AB - A 10-year-old, neutered male, Basset hound had a 26 * 21 * 21 cm infiltrative mass on the left abdominal wall that did not extend into the peritoneal cavity based on radiographs and abdominal computed tomography. Cytological examination revealed moderate numbers of neoplastic round cells, which frequently contained numerous round, clear, cytoplasmic vacuoles. Histologically, the tumour was composed of two morphologically distinct cell populations forming a continuum of heterogeneously differentiated cells. The primary spindle-shaped population formed streams with abundant, lightly eosinophilic, alcian blue-positive, myxoid matrix. The second population was arranged in sheets and had a round cell appearance. Scattered within both populations were neoplastic cells containing variably sized, intracytoplasmic, osmium tetroxide-positive vacuoles (lipid). Multifocal large pools of mucin formed pseudocysts, and numerous small capillaries were present throughout the neoplasm. According to the current World Health Organization veterinary classification of liposarcomas, this neoplasm had morphological features of both the myxoid and pleomorphic variants of liposarcoma; however, it was analogous to the recently defined high-grade myxoid liposarcoma in man. Myxoid liposarcoma with round cells has not been described previously in dogs. This case highlights the need to potentially re-evaluate the current classification of liposarcomas in animals. PMID- 27665043 TI - Association of Lower Quarter Y-Balance Test with lower extremity injury in NCAA Division 1 athletes: an independent validation study. AB - OBJECTIVES: To determine if the Lower Quarter Y-Balance Test (LQYBT) is predictive of lower extremity injury in NCAA Division 1 athletes. DESIGN: Prospective cohort, therapy. PARTICIPANTS: One hundred eighty-nine NCAA Division 1 athletes participated in the study and underwent a preparticipation screen that included the LQYBT. Maximal reach distances were recorded in each direction and normalized to leg length. A composite score was calculated by summing the three normalized reach distances and dividing by three times leg length. Side to side asymmetry was calculated as the lesser of the two composite scores, divided by the greater of the two composite scores, multiplied by 100. Injuries for the following season were tracked and recorded; LQYBT scores were compared between injured and non-injured athletes. RESULTS: In our sample, 90 [59 female, 31 male] of the 189 athletes participating suffered a lower extremity injury. No significant differences were found between injured and non-injured athletes for reach distance, normalized reach distance, normalized composite reach distance, or normalized composite percent score (P>0.05). CONCLUSIONS: The LQYBT does not appear to predict general lower extremity injury in a diverse population of NCAA D1 athletes. These results are in direct conflict with previous findings suggesting the LQYBT is predictive of injury suggesting its utility as an injury risk screening tool in a general collegiate athletic population should continue to be questioned. PMID- 27665044 TI - Growth and photosynthetic limitation analysis of the Cd-accumulator Salicornia ramosissima under excessive cadmium concentrations and optimum salinity conditions. AB - Cadmium (Cd) is a non-essential element for plants, and its excess impairs plant performance. Physiological impacts of Cd excess are well known in non-tolerant plants, however this information is scarce for Cd-tolerant plants. A glasshouse experiment was designed to investigate the effect of five different Cd levels (0, 0.05, 0.20, 0.65 and 1.35 mM Cd) on the growth, photosynthetic apparatus (PSII chemistry), gas exchange characteristics, photosynthetic pigments profiles, water relations and nutritional balance of the Cd-accumulator Salicornia ramosissima. Ours results confirmed the accumulation capacity of S. ramosissima, as indicated the bioaccumulation factor (BC) greater than 1.0 for all Cd levels. Furthermore, after 21 days of treatment S. ramosissima growth was not highly affected by Cd. Total photosynthetic limitation increased from 38% at 0.05 mM Cd to 70% at 1.35 mM Cd. CO2 diffusion restriction imposed the main contribution to total photosynthetic limitation. Mesophyll conductance reduction was of major importance (with between 69 and 86%), followed by stomatal conductance (with between 9 and 20%). Maximum carboxylation rate (Vc,max), remained stable until 0.2 mM Cd, and chlorophyll fluorescence parameters (Fv/Fm, qP) and pigments concentrations were not significantly decreased by increased Cd supply. Finally, S. ramosissima water relations (intrinsic water use efficiency and relative water content) and nutritional level did not highly vary between Cd treatments. Thus, our finding suggested that Cd tolerance S. ramosissima is in certain degree supported by the tolerance of its carbon assimilation enzyme (RuBisCO) and with the high functionality and integrity of the PSII reaction center under Cd excess. PMID- 27665047 TI - Editorial commentary: Anti-glycemic drugs and heart failure-A new era. PMID- 27665045 TI - Proteomic comparison of near-isogenic barley (Hordeum vulgare L.) germplasm differing in the allelic state of a major senescence QTL identifies numerous proteins involved in plant pathogen defense. AB - Senescence is the last developmental phase of plant tissues, organs and, in the case of monocarpic senescence, entire plants. In monocarpic crops such as barley, it leads to massive remobilization of nitrogen and other nutrients to developing seeds. To further investigate this process, a proteomic comparison of flag leaves of near-isogenic late- and early-senescing barley germplasm was performed. Protein samples at 14 and 21 days past anthesis were analyzed using both two dimensional gel-based and label-free quantitative mass spectrometry-based ('shotgun') proteomic techniques. This approach identified >9000 barley proteins, and one-third of them were quantified. Analysis focused on proteins that were significantly (p < 0.05; difference >=1.5-fold) upregulated in early-senescing line '10_11' as compared to late-senescing variety 'Karl', as these may be functionally important for senescence. Proteins in this group included family 1 pathogenesis-related proteins, intracellular and membrane receptors or co receptors (NBS-LRRs, LRR-RLKs), enzymes involved in attacking pathogen cell walls (glucanases), enzymes with possible roles in cuticle modification, and enzymes involved in DNA repair. Additionally, proteases and elements of the ubiquitin proteasome system were upregulated in line '10_11', suggesting involvement of nitrogen remobilization and regulatory processes. Overall, the proteomic data highlight a correlation between early senescence and upregulated defense functions. This correlation emerges more clearly from the current proteomic data than from a previously performed transcriptomic comparison of 'Karl' and '10_11'. Our findings stress the value of studying biological systems at both the transcript and protein levels, and point to the importance of pathogen defense functions during developmental leaf senescence. PMID- 27665048 TI - Sudden cardiac death: A reappraisal. AB - Sudden cardiac death (SCD) is still among the leading causes of death in women and men, accounting for over 50% of all fatal cardiovascular events in the United States. Two arrhythmia mechanisms of SCD can be distinguished as follows: shockable rhythms (ventricular fibrillation and pulseless ventricular tachycardia) and non-shockable rhythms including asystole or pulseless electrical activity. The overall prognosis of cardiac arrest due to shockable rhythms is significantly better. While the majority of SCDs is attributed to coronary artery disease or other structural heart disease, no obvious cause can be identified in 5% of all events, and those events are labeled as sudden unexplained deaths (SUD). Those unexplained events are typically caused by rare hereditary electrical disorders or arrhythmogenic cardiomyopathies. A systematic approach to the diagnosis of cardiac arrest followed by tailored therapy based on etiology has emerged in the last 10-15 years, with significant changes of medical practice and risk management of cardiac arrest victims. The aim of this review is to summarize our contemporary understanding of SCD/SUD in adults and to discuss current concepts of management and secondary prevention in cardiac arrest victims. A full discussion of the topic of primary prevention of SCD is beyond the scope of this article. PMID- 27665049 TI - Serum TGF-beta1: A Potential Biomarker for Early Detection of Hepatocellular Carcinoma. PMID- 27665051 TI - Glucagon-secretion inhibition using somatostatin: An old hormone for the treatment of diabetes-associated pancreatectomy. PMID- 27665052 TI - Short-term effect of severe hypoglycaemia on glycaemic control in the Diabetes Control and Complications Trial. PMID- 27665050 TI - Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale. The control group (n=28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n=23), moTBI (n=7), mTBI (n=37) patients and controls (n=27). We show that two medium chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC=0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified 'TBI metabotype' in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs. PMID- 27665053 TI - Should patients with early breast cancer still be offered the choice of breast conserving surgery or mastectomy? AB - Breast conserving therapy (BCT) for breast cancer aims to achieve long-term local disease control with reduced local morbidity. BCT has similar long-term survival outcomes to mastectomy in patients with early breast cancer and recent studies have reported similar rates of recurrence compared with mastectomy. An increasing number of studies have shown improved overall survival among women treated with BCT regardless of cancer phenotype compared with mastectomy. Despite BCT being at least equivalent in outcome to mastectomy many women with small breast cancers continue to be treated by mastectomy and several studies in the last decade have shown a trend of increasing numbers of unilateral and bilateral mastectomies. The advent of increasingly effective neoadjuvant treatment has allowed even more women to have breast conservation. Not only has neoadjuvant therapy been shown to increase the rates of BCT, it does so without increasing in breast recurrence rates. Patients who are suitable for BCT should be advised that BCT is the best treatment option for them. They should be informed that not only does it confer at least equivalent survival and local recurrence rates but that compared with mastectomy it has the advantages of less complications, better quality of life and many less operations if reconstructive surgery is performed. It may no longer be appropriate to offer women suitable for BCT the choice of mastectomy or BCT. PMID- 27665054 TI - Regarding: "The dosimetric impact of image guided radiation therapy by intratumoral fiducial markers". PMID- 27665055 TI - Morphokinetics of human blastocyst expansion in vitro. AB - Time-lapse imaging offers new tools to study dynamic processes of development such as blastocyst formation and expansion. This study quantitatively describes expansion in human blastocysts from donated oocytes. Measurements of hourly interval rate of changes in the blastocoel cross-sectional area revealed oscillatory pulses having 2-4 h periodicities. Two types of oscillations were distinguished. An E-Type ('expansion') had positive peak and positive or slightly negative trough interval rate of change values, and these characterized most of the expansion period. A C-type ('contraction') represented an infrequent but notable contraction of the blastocoel with loss of blastocoel fluid. These were reversible within 2-4 h in both groups and followed by further expansion. Therefore, oscillatory pulses are an intrinsic property of the trophectoderm. The zona seems to variably dampen the amplitude of these pulses. Expansion kinetics were compared between blastocysts with known positive (KID+) or negative (KID-) implantation outcomes. Regression analysis suggests that expansion may be relatively restricted in KID- embryos blastulating at relatively later times. These data extend observations in other mammalian systems and may provide information useful for clinical selection algorithms. PMID- 27665056 TI - Commentary re: Causes and estimated incidences of sex-chromosome misdiagnosis in preimplantation genetic diagnosis of aneuploidy. PMID- 27665057 TI - Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons. AB - Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98). At 4 years, cognition (Kaufmann-ABC-II; total IQ) and behaviour (Child Behavior Checklist; total problem T-score) were assessed. Causal inference search algorithms and structural equation modelling was applied to unravel causal mechanisms. Most children had typical cognitive and behavioural scores. No underlying causal effect was found between ovarian stimulation and the in-vitro procedure and outcome. Direct negative causal effects were found between severity of subfertility (time to pregnancy) and cognition and presence of subfertility and behaviour. Maternal age and maternal education acted as confounders. The study concludes that no causal effects were found between ovarian stimulation or in-vitro procedures and cognition and behaviour in childrenaged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour. PMID- 27665058 TI - A location-to-segmentation strategy for automatic exudate segmentation in colour retinal fundus images. AB - The automatic exudate segmentation in colour retinal fundus images is an important task in computer aided diagnosis and screening systems for diabetic retinopathy. In this paper, we present a location-to-segmentation strategy for automatic exudate segmentation in colour retinal fundus images, which includes three stages: anatomic structure removal, exudate location and exudate segmentation. In anatomic structure removal stage, matched filters based main vessels segmentation method and a saliency based optic disk segmentation method are proposed. The main vessel and optic disk are then removed to eliminate the adverse affects that they bring to the second stage. In the location stage, we learn a random forest classifier to classify patches into two classes: exudate patches and exudate-free patches, in which the histograms of completed local binary patterns are extracted to describe the texture structures of the patches. Finally, the local variance, the size prior about the exudate regions and the local contrast prior are used to segment the exudate regions out from patches which are classified as exudate patches in the location stage. We evaluate our method both at exudate-level and image-level. For exudate-level evaluation, we test our method on e-ophtha EX dataset, which provides pixel level annotation from the specialists. The experimental results show that our method achieves 76% in sensitivity and 75% in positive prediction value (PPV), which both outperform the state of the art methods significantly. For image-level evaluation, we test our method on DiaRetDB1, and achieve competitive performance compared to the state of the art methods. PMID- 27665059 TI - Drug-drug interactions between immunosuppressants and antidiabetic drugs in the treatment of post-transplant diabetes mellitus. AB - Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT) 2 inhibitors. Currently available data, although limited, suggest that these increases are modest and, particularly with regard to gliptins and SGLT-2 inhibitors, unlikely to result in hypoglycemia. The interaction with repaglinide is more pronounced but does not preclude concomitant use if repaglinide dose is gradually titrated. Mycophenolate mofetil and azathioprine do not engage in DDIs with any antidiabetic drug. Although calcineurin inhibitors (CNIs) and mammalian target of rapamycin inhibitors (mTORi) are intrinsically prone to DDIs, their disposition is not influenced by metformin, pioglitazone, sulfonylureas (except possibly glyburide) or insulin. An effect of gliptins on the disposition of CNIs and mTORi is unlikely, but has not been definitively ruled out. Based on their disposition profiles, glyburide and canagliflozin could affect CNI and mTORi disposition although this requires further study. Finally, delayed gastric emptying as a result of glucagon-like peptide-1 agonists seems to have a limited, but not necessarily negligible effect on CNI disposition. PMID- 27665060 TI - Towards an evaluation framework for Laboratory Information Systems. AB - INTRODUCTION: Laboratory testing and reporting are error-prone and redundant due to repeated, unnecessary requests and delayed or missed reactions to laboratory reports. Occurring errors may negatively affect the patient treatment process and clinical decision making. Evaluation on laboratory testing and Laboratory Information System (LIS) may explain the root cause to improve the testing process and enhance LIS in supporting the process. This paper discusses a new evaluation framework for LIS that encompasses the laboratory testing cycle and the socio-technical part of LIS. METHODOLOGY: Literature review on discourses, dimensions and evaluation methods of laboratory testing and LIS. A critical appraisal of the Total Testing Process (TTP) and the human, organization, technology-fit factors (HOT-fit) evaluation frameworks was undertaken in order to identify error incident, its contributing factors and preventive action pertinent to laboratory testing process and LIS. RESULT: A new evaluation framework for LIS using a comprehensive and socio-technical approach is outlined. Positive relationship between laboratory and clinical staff resulted in a smooth laboratory testing process, reduced errors and increased process efficiency whilst effective use of LIS streamlined the testing processes. CONCLUSION: The TTP-LIS framework could serve as an assessment as well as a problem-solving tool for the laboratory testing process and system. PMID- 27665061 TI - The allosteric citalopram binding site differentially interferes with neuronal firing rate and SERT trafficking in serotonergic neurons. AB - Citalopram is a clinically applied selective serotonin re-uptake inhibitor for antidepressant pharmacotherapy. It consists of two enantiomers, S-citalopram (escitalopram) and R-citalopram, of which escitalopram exerts the antidepressant therapeutic effect and has been shown to be one of the most efficient antidepressants, while R-citalopram antagonizes escitalopram via an unknown molecular mechanism that may depend on binding to a low-affinity allosteric binding site of the serotonin transporter. However, the precise mechanism of antidepressant regulation of the serotonin transporter by citalopram enantiomers still remains elusive. Here we investigate escitalopram's acute effect on (1) serotonergic neuronal firing in transgenic mice that express the human serotonin transporter without and with a mutation that disables the allosteric binding site, and (2) regulation of the serotonin transporter's cell surface localization in stem cell-derived serotonergic neurons. Our results demonstrate that escitalopram inhibited neuronal firing less potently in the mouse line featuring a mutation that abolishes the function of the allosteric binding site and induced serotonin transporter internalization independently of the allosteric binding site mechanism. Furthermore, citalopram enantiomers dose-dependently induced serotonin transporter internalization. In conclusion, this study provides new insight into antidepressant effects exerted by citalopram enantiomers in presence and absence of a functional allosteric binding site. PMID- 27665062 TI - The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder. AB - There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to 'normalise' global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium. PMID- 27665064 TI - Revisiting the understanding of "transactional sex" in sub-Saharan Africa: A review and synthesis of the literature. AB - In sub-Saharan Africa, young women ages 15-24 have more than twice the risk of acquiring HIV as their male counterparts. A growing body of epidemiological evidence suggests that the practice of "transactional sex" may contribute to this disparity. Over the last 15 years, the social sciences have contributed significantly to understanding the meaning of and motivations for this practice. The findings from these studies are rich, but varied, rendering lessons difficult to navigate for intervention and further research. We therefore contribute a historically-grounded, comprehensive literature review on the nature and motivations for women's participation in transactional sex in sub-Saharan Africa. Drawing from over 300 studies (through 2014), we distill three prominent paradigms observed in the literature that we review toward presenting a unified conceptualization of the practice. "Sex for basic needs," the first paradigm, positions women as victims in transactional sexual relationships, with implications for interventions that protect girls from exploitation. In contrast, the "sex for improved social status" paradigm positions women as sexual agents who engage in transactional sex toward attaining a middle-class status and lifestyle. Finally, a third paradigm, "sex and material expressions of love," draws attention to the connections between love and money, and the central role of men as providers in relationships. We find important commonalities in the structural factors that shape the three paradigms of transactional sex including gender inequality and processes of economic change. We suggest that there are three continua stretching across these paradigms: deprivation, agency, and instrumentality. This review proposes a definition of transactional sex and discusses implications for research and interventions aiming to reduce young women's risk of HIV through such relationships. We consider the consequences of drawing from too narrow an understanding of the practice, and highlight the benefits of a broader conceptualization. PMID- 27665063 TI - Hitchhiking: A Non-Canonical Mode of Microtubule-Based Transport. AB - The long-range movement of organelles, vesicles, and macromolecular complexes by microtubule-based transport is crucial for cell growth and survival. The canonical view of intracellular transport is that each cargo directly recruits molecular motors via cargo-specific adaptor molecules. Recently, a new paradigm called 'hitchhiking' has emerged: some cargos can achieve motility by interacting with other cargos that have already recruited molecular motors. In this way, cargos are co-transported together and their movements are directly coupled. Cargo hitchhiking was discovered in fungi. However, the observation that organelle dynamics are coupled in mammalian cells suggests that this paradigm may be evolutionarily conserved. We review here the data for hitchhiking and discuss the biological significance of this non-canonical mode of microtubule-based transport. PMID- 27665065 TI - Does persistent HIV replication explain continued lymphoma incidence in the era of effective antiretroviral therapy? AB - Non-Hodgkin lymphomas are highly increased in incidence in individuals infected with HIV, and this continues to be the case in spite of highly effective combined antiretroviral therapy (cART). New evidence has demonstrated that while successful virtual recovery of CD4 counts and elimination of HIV from peripheral blood can be achieved with cART, viral replication can still occur in lymphoid tissues. In addition, recent studies have suggested that adipose tissue provides an additional reservoir for HIV-infected macrophages and T lymphocytes even in the context of successful cART therapy. In this review article, we discuss possible mechanisms leading to the development of lymphoma in the cART era. PMID- 27665066 TI - A hybrid method for evaluating enterprise architecture implementation. AB - Enterprise Architecture (EA) implementation evaluation provides a set of methods and practices for evaluating the EA implementation artefacts within an EA implementation project. There are insufficient practices in existing EA evaluation models in terms of considering all EA functions and processes, using structured methods in developing EA implementation, employing matured practices, and using appropriate metrics to achieve proper evaluation. The aim of this research is to develop a hybrid evaluation method that supports achieving the objectives of EA implementation. To attain this aim, the first step is to identify EA implementation evaluation practices. To this end, a Systematic Literature Review (SLR) was conducted. Second, the proposed hybrid method was developed based on the foundation and information extracted from the SLR, semi structured interviews with EA practitioners, program theory evaluation and Information Systems (ISs) evaluation. Finally, the proposed method was validated by means of a case study and expert reviews. This research provides a suitable foundation for researchers who wish to extend and continue this research topic with further analysis and exploration, and for practitioners who would like to employ an effective and lightweight evaluation method for EA projects. PMID- 27665068 TI - Dissecting stem cell differentiation using single cell expression profiling. AB - Many assumptions about the way cells behave are based on analyses of populations. However, it is now widely recognized that even apparently pure populations can display a remarkable level of heterogeneity. This is particularly true in stem cell biology where it hinders our understanding of normal development and the development of strategies for regenerative medicine. Over the past decade technologies facilitating gene expression analysis at the single cell level have become widespread, providing access to rare cell populations and insights into population structure and function. Here we review the contributions of single cell biology to understanding stem cell differentiation so far, both as a new methodology for defining cell types and a tool for understanding the complexities of cellular decision-making. PMID- 27665067 TI - Results from a psychometric assessment of a new tool for measuring evidence-based decision making in public health organizations. AB - BACKGROUND: In order to better understand how to improve evidence-based decision making (EBDM) in state health departments, measurement tools are needed to evaluate changes in EBDM. The purpose of this study was to test the psychometric properties of a new measurement tool to assess EBDM in public health practice settings. METHODS: A questionnaire was developed, pilot-tested and refined in an iterative process with the input of public health practitioners with the aim of identifying a set of specific measures representing different components of EBDM. Data were collected in a national survey of state health department chronic disease practitioners. The final dataset (n=879) for psychometric testing was comprised of 19 EBDM items that were first examined using exploratory factor analysis, and then confirmatory factor analysis. RESULTS: The final model from confirmatory factor analysis includes five latent factors representing components of EBDM: capacity for evaluation, expectations and incentives for EBDM, access to evidence and resources for EBDM, participatory decision making, and leadership support and commitment. CONCLUSIONS: This study addresses the need for empirically tested and theory-aligned measures that may be used to assess the extent to which EBDM is currently implemented, and further, to gauge the success of strategies to improve EBDM, in public health settings. This EBDM measurement tool may help identify needed supports for enhanced capacity and implementation of effective strategies. PMID- 27665070 TI - Development of a Tool to Measure Nurse Clinical Judgment During Maternal Mortality Case Review. AB - National task forces have been charged to reduce maternal mortality rates. To do so, they must identify the role of the nurse in accomplishing this goal, but the specific assessments and interventions for which only nurses are responsible have yet to be defined. Clinical judgment, which is the ability to notice, interpret, and respond to potential problems, is a core nurse function. Nurse clinical judgment can be evaluated during chart review with new available tools. PMID- 27665069 TI - Bacterial diversity analysis of pork longissimus lumborum following long term ohmic cooking and water bath cooking by amplicon sequencing of 16S rRNA gene. AB - The bacterial ecology of long term ohmic- (LTOH) and water bath- (WB) cooked pork longissimus lumborum during refrigerated storage was investigated by culture dependent and amplicon sequencing of 16S rRNA gene. High bacterial diversity was observed in both LTOH- and WB-cooked meat, and the diversity decreased with prolonged storage, however, it was more complex in LTOH-cooked meat compared with WB treated ones. Bacillus, Pseudomonas, Enterococcus and Lactococcus were the most prevalent genera in the first two weeks and were replaced by Carnobacterium by the end of storage. Brevundimonas, Bacteroidaceae, Lactobacillaceae, uncultured Clostridiales Family_XIII, Alcaligenaceae and Micrococcales were more abundant in LTOH-cooked meat, while only Moraxellaceae were more abundant in WB cooked samples. The different abundances may have resulted from the reaction of bacteria to different heating mechanisms. Overall, LTOH-cooked meat has a similar shelf-life with shorter processing time compared to WB treated ones. PMID- 27665071 TI - Inhibition of return shortens perceived duration of a brief visual event. AB - We investigated the influence of attentional inhibition on the perceived duration of a brief visual event. Although attentional capture by an exogenous cue is known to prolong the perceived duration of an attended visual event, it remains unclear whether time perception is also affected by subsequent attentional inhibition at the location previously cued by an exogenous cue, an attentional phenomenon known as inhibition of return. In this study, we combined spatial cuing and duration judgment. After one second from the appearance of an uninformative peripheral cue either to the left or to the right, a target appeared at a cued side in one-third of the trials, which indeed yielded inhibition of return, and at the opposite side in another one-third of the trials. In the remaining trials, a cue appeared at a central box and one second later, a target appeared at either the left or right side. The target at the previously cued location was perceived to last shorter than the target presented at the opposite location, and shorter than the target presented after the central cue presentation. Therefore, attentional inhibition produced by a classical paradigm of inhibition of return decreased the perceived duration of a brief visual event. PMID- 27665072 TI - The role of bullying in depressive symptoms from adolescence to emerging adulthood: A growth mixture model. AB - BACKGROUND: The present study sought to identify trajectories of depressive symptoms in adolescence and emerging adulthood using a school-based sample of adolescents assessed over a five-year period. The study also examined whether bully and cyberbully victimization and perpetration significantly predicted depressive symptom trajectories. METHOD: Data from a sample of 1042 high school students were examined. The sample had a mean age of 15.09 years (SD=.79), was 56.0% female, and was racially diverse: 31.4% Hispanic, 29.4% White, and 27.9% African American. Data were examined using growth mixture modeling. RESULTS: Four depressive symptoms trajectories were identified, including those with a mild trajectory of depressive symptoms, an increasing trajectory of depressive symptoms, an elevated trajectory of depressive symptoms, and a decreasing trajectory of depressive symptoms. Results indicated that bully victimization and cyberbully victimization differentially predicted depressive symptoms trajectories across adolescence, though bully and cyberbully perpetration did not. LIMITATIONS: Limitations include reliance on self-reports of bully perpetration and a limited consideration of external factors that may impact the course of depression. CONCLUSIONS: These findings may inform school personnel in identifying students' likely trajectory of depressive symptoms and determining where depression prevention and treatment services may be needed. PMID- 27665073 TI - Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development. AB - BACKGROUND: Maternal stress is associated with impairments in the neurodevelopment of offspring; however, the effects of the timing of exposure to maternal stress on a child's neurodevelopment are unclear. METHODS: In 2010, we studied 225 mother-child pairs in Shanghai, recruiting mothers in mid-to-late pregnancy and monitoring offspring from birth until 30 months of age. Maternal stress was assessed prenatally (at 28-36 weeks of gestation) and postnatally (at 24-30 months postpartum) using the Symptom-Checklist-90-Revised Scale (SCL-90-R) and Life-Event-Stress Scale to evaluate mothers' emotional stress and life event stress levels, respectively. Children's cognition and temperament were assessed at 24-30 months of age using the Gesell Development Scale and Toddler Temperament Scale, respectively. Multi-variable linear regression models were used to associate prenatal and postnatal stress with child cognitive and temperamental development. RESULTS: Maternal prenatal and postnatal Global Severity Index (GSI) of SCL-90-R were moderately correlated (ICC r=0.30, P<0.001). After adjusting for relevant covariates, the increase in prenatal GSI was associated with decreases in toddlers' gross motor, fine motor, adaptive and social behavior development independently of postnatal GSI, while the increase in postnatal GSI was associated with changes in multiple temperament dimensions independently of prenatal GSI. The effects of prenatal and postnatal depression scores of SCL-90-R were similar to those of GSI. LIMITATION: Relatively small sample size. CONCLUSIONS: Compared with postnatal exposure, children's cognitive development may be more susceptible to prenatal exposure to maternal emotional stress, whereas temperamental development may be more affected by postnatal exposure to maternal emotional stress compared with prenatal exposure. PMID- 27665074 TI - Autophagy in MCF-7 cancer cells induced by copper complexes. AB - BACKGROUND: Autophagy plays an important role in cancer cells. Targeting autophagy in cancer can provide new opportunities for drug development. METHODS: In this study we tested four Schiff base Cu(II) complexes against human breast cancer cells (MCF-7) and human non-cancerous cells (HEK-293T). We have tested their cytotoxic effect by evaluating IC50 using MTT test. To detect morphological changes of the actin fibers we have used fluorescent microscopy. To determine the type of cell death we used electrophoretic analysis and western blot analysis (protein LC3). RESULTS: IC50 values of the complexes increased with time of their influence, indicating acquired resistance of MCF-7 to the complexes. Healthy cells HEK-293T were not sensitive to the Cu(II) complexes. Compared with the control cells (cells without Cu(II) complexes) which were without morphological changes of actin fibers, Cu(II) complexes induced condensation and asymmetric conformational changes in actin filaments. To examine the type of cell death induced by the Cu(II) complexes we treated MCF-7 cells with Cu(II) complexes (1, 10, 50 and 100MUmol/L) during a 72h incubation period. By electrophoresis we have not detected any DNA fragmentation. To determine whether Cu(II) complexes induced autophagy or necrotic cell death we used the western blot analysis. MCF-7 cells influenced with tested Cu(II) complexes produced LC3 protein after their 72h incubation indicating autophagy in MCF-7 cancer cells. CONCLUSIONS: Tested Schiff base copper (II) complexes have antiproliferative activity against cancer cells but not against healthy cells. They have induced autophagy in the cancer cell line MCF-7. PMID- 27665075 TI - Green synthesis of palladium nanoparticles mediated by black tea leaves (Camellia sinensis) extract: Catalytic activity in the reduction of 4-nitrophenol and Suzuki-Miyaura coupling reaction under ligand-free conditions. AB - The present study was conducted to synthesize palladium nanoparticles (Pd NPs) through a facile and green route using non-toxic and renewable natural black tea leaves (Camellia sinensis) extract, as the reducing and stabilizing agent. The as prepared Pd@B.tea NPs catalyst was characterized by UV-vis spectroscopy, X-ray diffraction (XRD), fourier transformed infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). The Pd@B.tea NPs catalyst could be used as an efficient and heterogeneous catalyst for Suzuki coupling reactions between phenylboronic acid and a range of aryl halides (X=I, Br, Cl) and also the reduction of 4-nitrophenol (4-NP) using sodium borohydride in an environmental friendly medium. Excellent yields of products were obtained with a wide range of substrates and the catalyst was recycled 7 times without any significant loss of its catalytic activity. PMID- 27665076 TI - Monolayers of poly(amido amine) dendrimers on mica - In situ streaming potential measurements. AB - The deposition of poly(amido amine) dendrimers on mica at various pHs was studied by the atomic force microscopy (AFM) and in situ streaming potential measurements. Bulk characteristics of dendrimers were acquired by using the dynamic light scattering (DLS) and the laser Doppler velocimetry (LDV). The hydrodynamic radius derived from DLS measurements was 5.2nm for the ionic strength of 10-2M and pH range 4-10. The electrophoretic mobility, the zeta potential and the number of electrokinetic charges per molecule were derived as a function of pH from the LDV measurements. It was revealed that the dendrimers are positively charged for pH up to 10. This promoted their deposition on negatively charged mica substrate whose kinetics was quantitatively evaluated by direct AFM imaging and streaming potential measurements interpreted in terms of the electrokinetic model. The desorption kinetics of dendrimers under flowing conditions from monolayers of various coverage was also studied. It was revealed that dendrimer deposition was partially reversible for pH above 5.8. The acid base properties of the dendrimer monolayers deposited on mica were characterized. PMID- 27665077 TI - Carbon disulfide mediated self-assembly of Laccase and iron oxide nanoparticles on gold surfaces for biosensing applications. AB - A simple one-step methodology was explored to prepare enzyme-modified nanostructured electrodes for the development of biosensing interfaces. Magnetite type nanoparticles conjugated with Laccase were immobilized on gold surfaces. This approach relies on the reaction between carbon disulfide and amine groups of biomolecules to form dithiocarbamate (DTC) moieties, as well as on the strong affinity between sulfur species and metals. Special emphasis was given to demonstrate DTC formation in aqueous solution and further attachment to iron oxide nanoparticles and to gold electrodes. UV-visible spectroscopy confirmed the functionalization of nanoparticles by DTC using a model secondary amine (N hexylmethylamine). The direct attachment of modified iron oxide nanoparticles (with ca. 20 or 40nm mean sizes) to gold electrodes was investigated using the hormone epinephrine, with well-known electrochemical properties. A high amount of immobilized epinephrine and a facilitated redox conversion was observed for modified electrodes containing iron oxide nanoparticles. The success of this simple and robust method was confirmed by X-ray photoelectronic spectroscopy. Finally, the catalytic activity of modified gold with iron oxide nanoparticles and Laccase was evaluated toward 2,2'-azino-bis (3-ethylbenzothiazoline-6 sulfonic acid diammonium salt (ABTS). Chronoamperometric studies revealed a significant catalytic activity of immobilized Laccase in the presence of the nanoparticles, in particular for the largest ones (40nm), with a sensitivity for ABTS oxidation of 100mAM-1cm-2. PMID- 27665079 TI - Neurologic sequelae associated with delayed identification of iatrogenic skull base injury during endoscopic sinus surgery (ESS). AB - BACKGROUND: Skull base injury is an infrequent complication during endoscopic sinus surgery (ESS). We hypothesize that late recognition and repair of CSF leaks during ESS is associated with increased neurologic morbidity. METHODOLOGY: A retrospective review was performed of patients with skull base injury during ESS at a tertiary center from 1999-2015. The study population was separated into early (less than 72 hrs) and late (more than 72 hrs) intervention groups. Study parameters included time to diagnosis, imaging, site of injury, type of repair, neurologic complications, and clinical outcomes. RESULTS: Seventeen patients were studied. The primary surgical interventions included ESS and balloon sinuplasty. Mean latency from primary surgery to presentation to our facility was 11 days. The most common injury site was the cribriform plate and the mean defect size 4.5 mm. Late diagnosis was associated with increased total neurologic complications and increased rates of postoperative meningitis. No neurologic complications occurred in patients diagnosed intraoperatively. All patients underwent successful endoscopic repair. CONCLUSION: Skull base injury is a rare but major complication following both balloon sinuplasty and traditional primary ESS. Early diagnosis and endoscopic repair may prevent neurologic morbidity in these patients. PMID- 27665078 TI - Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord. AB - Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection. Eight weeks after transplantation, the neural network created a favorable microenvironment for axonal regeneration and for survival and synaptogenesis of NSC-derived neurons. Biotin conjugates of cholera toxin B subunit (b-CTB, a transneuronal tracer) was injected into the crushed sciatic nerve to label spinal cord neurons. Remarkably, not only ascending and descending nerve fibers, but also propriospinal neurons, made contacts with b-CTB positive NSC-derived neurons. Moreover, b-CTB positive NSC-derived neurons extended their axons making contacts with the motor neurons located in areas caudal to the injury/graft site of spinal cord. Further study showed that NT-3/TrkC interactions activated the PI3K/AKT/mTOR pathway and PI3K/AKT/CREB pathway affecting synaptogenesis of NSC derived neurons. Together, our findings suggest that NT-3-mediated TrkC signaling plays an essential role in constructing a tissue engineering neural network thus representing a promising avenue for effective exogenous neuronal relay-based treatment for SCI. PMID- 27665080 TI - Hypothalamic-pituitary-adrenal axis, childhood adversity and adolescent nonsuicidal self-injury. AB - BACKGROUND: Whereas childhood adversity (CA) and the hypothalamus-pituitary adrenal (HPA) axis have been suggested to play a major role in the etiology of non-suicidal self-injury (NSSI), no study has thus far investigated both its associations and interactions with adolescent NSSI. METHOD: We investigated CA (antipathy, neglect, physical, psychological, and sexual abuse) and indices of HPA axis activity (salivary and hair cortisol) in a clinical sample of 26 adolescents engaging in NSSI and 26 age- and gender-matched healthy controls (HC). We used standardized interviews for the assessment of CA (CECA), NSSI (SITBI-G), and axis I diagnoses (MINI-KID). Salivary cortisol sampling was surveyed using a monitoring system and instructed via telephone calls. RESULTS: Adolescents engaging in NSSI exhibited significantly higher cortisol awakening responses compared to HC. No differences were found with respect to the diurnal slope or hair cortisol. In the presence of CA, healthy adolescents showed flatted diurnal cortisol slopes while those engaging in NSSI exhibited significantly steeper ones. CONCLUSIONS: Our findings indicate that adolescents engaging in NSSI may exhibit a stronger cortisol awakening response, potentially in expectation of strain. However, elevated cortisol levels may not be maintained throughout the day, especially among adolescents with a history of CA. PMID- 27665081 TI - Differential effects of oxytocin on social sensitivity in two distinct breeds of dogs (Canis familiaris). AB - Dogs have been proven to show several human-analogue social behaviors, and recent research raises the possibility that the oxytocin system is related to these. However, despite dogs' general tendency to excel in the domain of social cognition, there is increasing evidence that dogs' ability to utilize human signals may vary with breed. Moreover, breeds may show differences not only in their 'inborn' communicative abilities, but also in their learning skills related to these. The aim of the present study was to explore breed differences and breed specific effects of oxytocin administration on different aspects of social responsiveness. Dogs from two markedly different breeds, Border Collies (cooperative workers) and Siberian Huskies (independent workers) were tested. After having received intranasal administration of oxytocin or placebo, subjects participated in three behavioral tests measuring social responsiveness. Our results show that there are several behavioral differences between the two breeds and also that there are differential effects of the oxytocin treatment. Border Collies were in general more susceptible to the 'social' effects of oxytocin compared to Siberian Huskies: after oxytocin administration they (1) looked more at the experimenter in the 'Unreachable food' situation, (2) looked more at the owner and shifted their gaze more between the sound source and the owner in a potentially dangerous situation, and (3) looked longer at the experimenter's eyes in the 'Tolerance of prolonged eye contact' test. These findings suggest that selection for enhanced cooperative abilities, possibly complemented by the effect of different social environments the two breeds experience, affects dogs' performance in several behavioral tests and that the neurohormonal background differently modulates social behavior in different working breeds. PMID- 27665082 TI - Preparation and characterization of chitosan based injectable hydrogels enhanced by chitin nano-whiskers. AB - The objective of current study was to prepare an injectable hydrogel with great mechanical properties and biological compatibility, which could be more suitable to be applied as tissue engineering scaffold. Chitin nano-whiskers (CNWs) were introduced into chitosan/beta-glycerophosphate disodium salt (CS/GP) injectable hydrogel. The effects of CNWs contents and gelation temperatures on gelation speed and mechanical properties of the composite hydrogels were characterized and discussed. The maximum values of tensile strength and elongation at break were both more than 4 times larger than that of neat CS/GP hydrogel. The gelation time of injectable hydrogel with 5% CNWs content (formed at 37 degrees C) was 25 seconds, which was much shorter than that (6038 seconds) of the neat CS/GP hydrogel. In combination with results of Fourier transform infrared spectroscopy (FT-IR), it was proved that CNWs functioned as a cross-linker through hydrogen bond interaction in the gel formation process, which might be the main reason for mechanical enhancement. Meanwhile, gels formed with higher CNWs content and gelation temperature had lower equilibrium swelling ratio and drug release rate. Cytotoxicity of hydrogel in vitro was studied by MTT method with a result of indicating a good biocompatibility of CNWs enhanced hydrogel. PMID- 27665083 TI - Mechanical response of 3D Insert(r) PCL to compression. AB - 3D polymeric scaffolds are increasingly used for in vitro experiments aiming to mimic the environment found in vivo, to support for cellular growth and to induce differentiation through the application of external mechanical cues. In research, experimental results must be shown to be reproducible to be claimed as valid and the first clause to ensure consistency is to provide identical initial experimental conditions between trials. As a matter of fact, 3D structures fabricated in batch are supposed to present a highly reproducible geometry and consequently, to give the same bulk response to mechanical forces. This study aims to measure the overall mechanical response to compression of commercially available 3D Insert PCL scaffolds (3D PCL) fabricated in series by fuse deposition and evaluate how small changes in the architecture of scaffolds affect the mechanical response. The apparent elastic modulus (Ea) was evaluated by performing quasi-static mechanical tests at various temperatures showing a decrease in material stiffness from 5MPa at 25 degrees C to 2.2MPa at 37 degrees C. Then, a variability analysis revealed variations in Ea related to the repositioning of the sample into the testing machine, but also consistent differences comparing different scaffolds. To clarify the source of the differences measured in the mechanical response, the same scaffolds previously undergoing compression, were scanned by micro computed tomography (MUCT) to identify any architectural difference. Eventually, to clarify the contribution given by differences in the architecture to the standard deviation of Ea, their mechanical response was qualitatively compared to a compact reference material such as polydimethylsiloxane (PDMS). This study links the geometry, architecture and mechanical response to compression of 3D PCL scaffolds and shows the importance of controlling such parameters in the manufacturing process to obtain scaffolds that can be used in vitro or in vivo under reproducible conditions. PMID- 27665085 TI - Determination of the in situ mechanical behavior of ankle ligaments. AB - The mechanical behavior of ankle ligaments at the structural level can be characterized by force-displacement curves in the physiologic phase up to the initiation of failure. However, these properties are difficult to characterize in vitro due to the experimental difficulties in replicating the complex geometry and non-uniformity of the loading state in situ. This study used a finite element parametric modeling approach to determine the in situ mechanical behavior of ankle ligaments at neutral foot position for a mid-sized adult foot from experimental derived bony kinematics. Nine major ankle ligaments were represented as a group of fibers, with the force-elongation behavior of each fiber element characterized by a zero-force region and a region of constant stiffness. The zero force region, representing the initial tension or slackness of the whole ligament and the progressive fiber uncrimping, was identified against a series of quasi static experiments of single foot motion using simultaneous optimization. A range of 0.33-3.84mm of the zero-force region was obtained, accounting for a relative length of 6.7+/-3.9%. The posterior ligaments generally exhibit high-stiffness in the loading region. Following this, the ankle model implemented with in situ ligament behavior was evaluated in response to multiple loading conditions and proved capable of predicting the bony kinematics accurately in comparison to the cadaveric response. Overall, the parametric ligament modeling demonstrated the feasibility of linking the gross structural behavior and the underlying bone and ligament mechanics that generate them. Determination of the in situ mechanical properties of ankle ligaments provides a better understanding of the nonlinear nature of the ankle joint. Applications of this knowledge include functional ankle joint mechanics and injury biomechanics. PMID- 27665086 TI - A cluster analysis of early onset in common anxiety disorders. AB - Early onset is regarded as an important characteristic of anxiety disorders, associated with higher severity. However, previous findings diverge, as definitions of early onset vary and are often unsubstantiated. We objectively defined early onset in social phobia, panic disorder, agoraphobia, and generalised anxiety disorder, using cluster analysis with data gathered in the general population. Resulting cut-off ages for early onset were <=22 (social phobia), <=31 (panic disorder), <=21 (agoraphobia), and <=27 (generalised anxiety disorder). Comparison of psychiatric comorbidity and general wellbeing between subjects with early and late onset in the general population and an outpatient cohort, demonstrated that among outpatients anxiety comorbidity was more common in early onset agoraphobia, but also that anxiety- as well as mood comorbidity were more common in late onset social phobia. A major limitation was the retrospective assessment of onset. Our results encourage future studies into correlates of early onset of psychiatric disorders. PMID- 27665084 TI - Characterizing white matter tissue in large strain via asymmetric indentation and inverse finite element modeling. AB - Characterizing the mechanical properties of white matter is important to understand and model brain development and injury. With embedded aligned axonal fibers, white matter is typically modeled as a transversely isotropic material. However, most studies characterize the white matter tissue using models with a single anisotropic invariant or in a small-strain regime. In this study, we combined a single experimental procedure - asymmetric indentation - with inverse finite element (FE) modeling to estimate the nearly incompressible transversely isotropic material parameters of white matter. A minimal form comprising three parameters was employed to simulate indentation responses in the large-strain regime. The parameters were estimated using a global optimization procedure based on a genetic algorithm (GA). Experimental data from two indentation configurations of porcine white matter, parallel and perpendicular to the axonal fiber direction, were utilized to estimate model parameters. Results in this study confirmed a strong mechanical anisotropy of white matter in large strain. Further, our results suggested that both indentation configurations are needed to estimate the parameters with sufficient accuracy, and that the indenter-sample friction is important. Finally, we also showed that the estimated parameters were consistent with those previously obtained via a trial-and-error forward FE method in the small-strain regime. These findings are useful in modeling and parameterization of white matter, especially under large deformation, and demonstrate the potential of the proposed asymmetric indentation technique to characterize other soft biological tissues with transversely isotropic properties. PMID- 27665087 TI - As we fall asleep we forget about the future: A quantitative linguistic analysis of mentation reports from hypnagogia. AB - We present a quantitative study of mental time travel to the past and future in sleep onset hypnagogia. Three independent, blind judges analysed a total of 150 mentation reports from different intervals prior to and after sleep onset. The linguistic tool for the mentation report analysis grounds on established grammatical and cognitive-semantic theories, and proof of concept has been provided in previous studies. The current results indicate that memory for the future, but not for the past, decreases in sleep onset - thereby supporting preliminary physiological evidence at the level of brain function. While recent memory research emphasizes similarities in the cognitive and physiological processes of mental time travel to the past and future, the current study explores a state of consciousness which may serve to dissociate between the two. PMID- 27665088 TI - Feasibility and reliability of using an exoskeleton to emulate muscle contractures during walking. AB - Contracture is a permanent shortening of the muscle-tendon-ligament complex that limits joint mobility. Contracture is involved in many diseases (cerebral palsy, stroke, etc.) and can impair walking and other activities of daily living. The purpose of this study was to quantify the reliability of an exoskeleton designed to emulate lower limb muscle contractures unilaterally and bilaterally during walking. An exoskeleton was built according to the following design criteria: adjustable to different morphologies; respect of the principal lines of muscular actions; placement of reflective markers on anatomical landmarks; and the ability to replicate the contractures of eight muscles of the lower limb unilaterally and bilaterally (psoas, rectus femoris, hamstring, hip adductors, gastrocnemius, soleus, tibialis posterior, and peroneus). Sixteen combinations of contractures were emulated on the unilateral and bilateral muscles of nine healthy participants. Two sessions of gait analysis were performed at weekly intervals to assess the reliability of the emulated contractures. Discrete variables were extracted from the kinematics to analyse the reliability. The exoskeleton did not affect normal walking when contractures were not emulated. Kinematic reliability varied from poor to excellent depending on the targeted muscle. Reliability was good for the bilateral and unilateral gastrocnemius, soleus, and tibialis posterior as well as the bilateral hamstring and unilateral hip adductors. The exoskeleton can be used to replicate contracture on healthy participants. The exoskeleton will allow us to differentiate primary and compensatory effects of muscle contractures on gait kinematics. PMID- 27665089 TI - Tyrosine phosphorylation modulates mitochondrial chaperonin Hsp60 and delays rotavirus NSP4-mediated apoptotic signaling in host cells. AB - Phosphoproteomics-based platforms have been widely used to identify post translational dynamics of cellular proteins in response to viral infection. The present study was undertaken to assess differential tyrosine phosphorylation during early hours of rotavirus (RV) SA11 infection. Heat shock proteins (Hsp60) were found to be enriched in the data set of RV-SA11 induced differentially tyrosine-phosphorylated proteins at 2 hr post infection (hpi). Hsp60 was further found to be phosphorylated by an activated form of Src kinase on 227th tyrosine residue, and tyrosine phosphorylation of mitochondrial chaperonin Hsp60 correlated with its proteasomal degradation at 2-2.5hpi. Interestingly, mitochondrial Hsp60 positively influenced translocation of the rotaviral nonstructural protein 4 to mitochondria during RV infections. Phosphorylation and subsequent transient degradation of mitochondrial Hsp60 during early hours of RV SA11 infection resulted in inhibition of premature import of nonstructural protein 4 into mitochondria, thereby delaying early apoptosis. Overall, the study highlighted one of the many strategies rotavirus undertakes to prevent early apoptosis and subsequent reduced viral progeny yield. PMID- 27665090 TI - Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability. AB - The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases. PMID- 27665091 TI - A Randomized Trial on the Efficacy of Topical Anesthesia for Pain Reduction during Frame Placement for Gamma Knife Radiosurgery. AB - BACKGROUND/AIMS: Frame application for gamma knife radiosurgery (GKR) may be perceived as painful by patients. This study was designed to assess the efficacy of EMLA (2.5% lidocaine/2.5% prilocaine) in pain reduction. METHODS: This was a prospective, randomized, and controlled trial approved by our institutional review board. Fifty-four patients undergoing outpatient GKR were divided into EMLA and placebo groups. Prior to frame placement, EMLA/placebo was applied to the patient's forehead. A visual analog scale (VAS) was used to measure pain during 4 intervals: frontal injections, occipital injections, frontal screw insertion, and overall discomfort. This study was designed to observe a difference of 1.0 on the VAS at a power of 95%. RESULTS: VAS for EMLA versus placebo for frontal injections (5.2 +/- 2.7 vs. 5.7 +/- 2.0, respectively; p < 0.45), back injections, (6.5 +/- 2.2 vs. 5.9 +/- 2.3, respectively; p < 0.30), frontal pins (4.6 +/- 2.7 vs. 4.6 +/- 2.2, respectively; p < 0.99), and overall discomfort (p < 0.29) were not significantly different. A comparison between back and frontal injections for EMLA (6.54 vs. 5.19, respectively; p < 0.16) and placebo (5.89 vs. 5.68, respectively; p < 0.69) showed no significant difference between group and location (p < 0.21). CONCLUSION: Application of EMLA did not significantly reduce pain when used preoperatively for frame fixation. EMLA is no longer used as part of our routine for patients undergoing GKR. PMID- 27665092 TI - Wolff: straight not curved. AB - It was 140 years ago that George von Meyer presented his anatomical diagrams of human bones to a meeting in Zurich. There he was told by Prof. Karl Culmann that the trabecular lines shown within the diagram of the upper femur closely resembled those lines of force which Culmann had determined with Graphic Statics to be passing through a curved, loaded Fairbairn crane. This drew the attention of Julius Wolff, who used this as the basis for his 'Trajectorial theory' which was widely accepted and, to date, has been the underlying basis for all biomechanical investigations of this region. Following Wolff and Culmann, the upper femur is considered to be a curved structure and is investigated as such. Unfortunately, this concept is wrong. The upper femur is not curved but is angular. It is formed by the junction of two straight bones, the femoral neck and the femoral shaft, as may be simply seen as the neck/shaft angle constructed on the antero-posterior radiograph of any normal femur. The internal trabecular bone forms only part of the load bearing structure of the femoral neck. The configuration of this trabecular substance in this region suggests that it is related specifically to the force present during flexion and extension movements of the hip joint. This being so, combined with the delayed timing of the appearance of the trabecular columns, it must be questioned as to whether the remodelling of the upper femur is in response to one or to two distinct forces. PMID- 27665093 TI - An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation. AB - PURPOSE: The function of the anterior cruciate ligament (ACL) patients' non injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often without appropriate control groups. We measured a broad array of neuromuscular functions between legs of ACL patients and compared outcomes to age, sex, and physical activity matched controls. METHODS: Thirty-two ACL-deficient patients (208 +/- 145 days post-injury) and active and less-active controls (N = 20 each) participated in the study. We measured single- and multi-joint neuromuscular function in both legs in each group and expressed the overall neuromuscular function in each leg by calculating a mean z-score across all neuromuscular measures. A group by leg MANOVA and ANOVA were performed to examine group and leg differences for the selected outcomes. RESULTS: After an ACL injury, duration ( 4.3 h/week) and level (Tegner activity score of -3.9) of sports activity decreased and was comparable to less-active controls. ACL patients showed bilateral impairments in the star excursion balance test compared to both control groups (P <= 0.004) and for central activation ratio compared to active controls (P <= 0.002). There were between-leg differences within each group for maximal quadriceps and hamstring strength, voluntary quadriceps activation, star excursion balance test performance, and single-leg hop distance (all P < 0.05), but there were no significant differences in quadriceps force accuracy and variability, knee joint proprioception, and static balance. Overall neuromuscular function (mean z-score) did not differ between groups, but ACL patients' non injured leg displayed better neuromuscular function than the injured leg (P < 0.05). CONCLUSIONS: Except for poorer dynamic balance and reduced quadriceps activation, ACL patients had no bilateral neuromuscular deficits despite reductions in physical activity after injury. Therapists can use the non-injured leg as a reference to assess the injured leg's function for tasks measured in the present study, excluding dynamic balance and quadriceps activation. Rehabilitation after an ACL injury should be mainly focused on the injured leg. LEVEL OF EVIDENCE: III. PMID- 27665094 TI - Outcome reporting following navigated high tibial osteotomy of the knee: a systematic review. AB - PURPOSE: This systematic review evaluates radiographic and clinical outcome reporting following navigated high tibial osteotomy (HTO). Conventional HTO was used as a control to compare outcomes and furthermore investigate the quality of evidence in studies reporting outcomes for navigated HTO. It was hypothesized that navigated HTO will show superior clinical and radiographic outcomes compared to conventional HTO. METHODS: Two independent reviewers searched PubMed, Ovid (MEDLINE), EMBASE, and Cochrane databases for studies reporting outcomes following navigated HTO. Titles, abstracts, and full-text were screened in duplicate using an a priori inclusion and exclusion criteria. Descriptive statistics were calculated using Minitab (r) statistical software. Methodological Index for Nonrandomized Studies (MINORS) and Cochrane Risk of Bias Scores were used to evaluate methodological quality. RESULTS: Thirty-four studies which involved 2216 HTOs were analysed in this review, 1608 (72.6 %) navigated HTOs and 608 (27.4 %) conventional HTOs. The majority of studies were of level IV evidence (16). Clinical outcomes were reported in knee and function scores or range of motion comparisons. Postoperative clinical and functional scores were improved by navigated HTO although it is not demonstrated if there is significant improvement compared to conventional HTO. Most common clinical outcome score reported was Lysholm scores (6) which report postoperative scores of 87.8 (standard deviation 5.9) and 88.8 (standard deviation 5.9) for conventional and navigation-assisted HTO, respectively. Radiographic outcomes reported commonly were weight-bearing mechanical axis, coronal plane angle, and posterior tibial slope angle in the sagittal plane. Studies have shown HTO gives significant correction of mechanical alignment and navigated HTO produces significantly less change in posterior tibial slope postoperatively compared to conventional. The mean MINORS for the 17 non-comparative studies was 9/16, and 15/24 for the 14 non-randomized comparative studies. CONCLUSION: Navigation HTO results in improved mechanical axis alignment and demonstrates significantly better control over the tibial slope angle change postoperatively compared to conventional methods; however, these improvements have not yet been reflected in clinical outcome scores. Overall the studies report HTO does create significantly improved knee scores and functions compared to patients' preoperative ratings regardless of technique. Future studies on HTO outcomes need to focus on consistency of outcome reporting. LEVEL OF EVIDENCE: IV. PMID- 27665096 TI - Using preoperative unsupervised cluster analysis of chronic rhinosinusitis to inform patient decision and endoscopic sinus surgery outcome. AB - The purpose of this study is to use unsupervised cluster methodology to identify phenotype and mucosal eosinophilia endotype subgroups of patients with medical refractory chronic rhinosinusitis (CRS), and evaluate the difference in quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) between these clusters for better surgical case selection. A prospective cohort study included 131 patients with medical refractory CRS who elected ESS. The Sino-Nasal Outcome Test (SNOT-22) was used to evaluate QOL before and 12 months after surgery. Unsupervised two-step clustering method was performed. One hundred and thirteen subjects were retained in this study: 46 patients with CRS without nasal polyps and 67 patients with nasal polyps. Nasal polyps, gender, mucosal eosinophilia profile, and prior sinus surgery were the most discriminating factors in the generated clusters. Three clusters were identified. A significant clinical improvement was observed in all clusters 12 months after surgery with a reduction of SNOT-22 scores. There was a significant difference in QOL outcomes between clusters; cluster 1 had the worst QOL improvement after FESS in comparison with the other clusters 2 and 3. All patients in cluster 1 presented CRSwNP with the highest mucosal eosinophilia endotype. Clustering method is able to classify CRS phenotypes and endotypes with different associated surgical outcomes. PMID- 27665097 TI - Para-CS pacing maneuver: further evidence of left atrionodal connections. PMID- 27665095 TI - Platelet-rich plasma in tendon-related disorders: results and indications. AB - PURPOSE: Platelet-rich plasma (PRP) is currently the most exploited strategy in the clinical practice to provide a regenerative stimulus for tendon healing. The aim of the present study was to systematically review the available evidence on the treatment of the main tendon disorders where PRP is currently applied. METHODS: A systematic review of the literature was performed on the use of PRP as a treatment for tendinopathies focusing on the following sites: Achilles tendon, patellar tendon, rotator cuff tendons, and lateral elbow tendons. The following inclusion criteria for relevant articles were used: clinical trials written in English language up to 21 June 2016 on the use of PRP in the conservative or surgical treatment of the aforementioned tendinopathies. RESULTS: The research identified the following clinical trials dealing with the application of PRP in the selected tendons: 19 papers on patellar tendon (6 being RCTs: 4 dealing with PRP conservative application and 2 surgical), 24 papers on Achilles tendon (4 RCTs: 3 conservative and 1 surgical), 29 on lateral elbow tendons (17 RCTs, all conservative), and 32 on rotator cuff (22 RCTs: 18 surgical and 3 conservative). CONCLUSION: Patellar tendons seem to benefit from PRP injections, whereas in the Achilles tendon, PRP application is not indicated neither as a conservative approach nor as a surgical augmentation. Lateral elbow tendinopathy showed an improvement in most of the high-level studies, but the lack of proven superiority with respect to the more simple whole-blood injections still questions its use in the clinical practice. With regard to rotator cuff pathology, the vast majority of surgical RCTs documented a lack of beneficial effects, whereas there is still inconclusive evidence concerning its conservative application in rotator cuff disorders. LEVEL OF EVIDENCE: Systematic review of level I-IV trials, Level IV. PMID- 27665098 TI - Predictors of intraoperative electrosurgery-induced implantable cardioverter defibrillator (ICD) detection. AB - BACKGROUND: In the USA, the number of people needing implantable cardioverter defibrillators (ICDs) has grown dramatically. Many ICD recipients will need to undergo a surgical procedure at some point following ICD implantation. Most surgeries involve the use of electrocautery. Currently, the effects of electrocautery-induced electromagnetic interference (EI-EMI) on ICDs are poorly understood. The aim of this study was to study EI-EMI using prospectively collected clinical data. METHODS: We analyzed prospectively collected ICD data from patients undergoing a surgical procedure at Mayo Clinic between 2011 and 2012. Information on clinical, device history, device interrogation pre- and post surgery, and surgical information were collected for all patients. ICDs were programmed with detections on and therapies off. The patients were then categorized into two groups: those with EI-EMI inappropriate arrhythmia detection and those without detection. The stored electrograms were reviewed. Clinical and device parameters were analyzed to identify predictors of EI-EMI. RESULTS: Of 103 patients studied, bipolar cautery did not induce EI-EMI (0/11 cases), whereas monopolar cautery resulted in noise detection in 11/92 procedures. Among 11 inappropriate episodes of detection, 10 had surgery at chest, neck, and upper extremity sites with cautery current across the ICD lead tip; 1 had abdominal surgery; and none had back or low extremity surgery. On average, the near-field electrogram amplitude values were greater than the far-field amplitude values. CONCLUSIONS: EI-EMI does not occur when bipolar cautery or monopolar cautery is used below the hips with the dispersive ground pad applied to the lower extremities. In contrast to external EMI, EI-EMI may be larger on near-field than far-field electrograms. PMID- 27665099 TI - Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review. AB - BACKGROUND: Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost effectiveness of this strategy is debated. METHODS: All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. RESULTS: Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1 year period to ?13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. CONCLUSIONS: Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy. PMID- 27665100 TI - Hepatitis B core-related antigen: a strong indicator for cessation of nucleos(t)ide analog therapy in patients with chronic hepatitis B. PMID- 27665101 TI - Combined aspirin and anticoagulant therapy in patients with atrial fibrillation. AB - The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events. PMID- 27665102 TI - Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity. AB - The possible association of intracellular Ca2+ with metastasis in human cancer cells is poorly understood. We have studied Ca2+ signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca2+ was measured using a membrane permeant fluorescent Ca2+-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca2+ oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively). In contrast, no such oscillations were observed in weakly/non metastatic LNCaP and MCF-7 cells, although a rise in the resting Ca2+ level could be induced by applying a high-K+ solution. Various parameters of the oscillations depended on extracellular Ca2+ and voltage-gated Na+ channel activity. Treatment with either tetrodotoxin (a general blocker of voltage-gated Na+ channels) or ranolazine (a blocker of the persistent component of the channel current) suppressed the Ca2+ oscillations. It is concluded that the functional voltage gated Na+ channel expression in strongly metastatic cancer cells makes a significant contribution to generation of oscillatory intracellular Ca2+ activity. Possible mechanisms and consequences of the Ca2+ oscillations are discussed. PMID- 27665103 TI - A noninvasive swallowing measurement system using a combination of respiratory flow, swallowing sound, and laryngeal motion. AB - : The assessment of swallowing function is important for the prevention of aspiration pneumonia. We developed a new swallowing monitoring system that uses respiratory flow, swallowing sound, and laryngeal motion. We applied this device to 11 healthy volunteers and 10 patients with dysphagia. Videofluoroscopy (VF) was conducted simultaneously with swallowing monitoring using our device. We measured laryngeal rising time (LRT), the time required for the larynx to elevate to the highest position, and laryngeal activation duration (LAD), the duration between the onset of rapid laryngeal elevation and the time when the larynx returned to the lowest position. In addition, we evaluated the coordination between swallowing and breathing. We found that LAD was correlated with a VF derived parameter, pharyngeal response duration (PRD) in healthy subjects (LAD: 959 +/- 259 ms vs. PRD: 1062 +/- 149 ms, r = 0.60); however, this correlation was not found in the dysphagia patients. LRT was significantly prolonged in patients (healthy subjects: 320 +/- 175 ms vs. PATIENTS: 465 +/- 295 ms, P < 0.001, t test). Furthermore, frequency of swallowing immediately after inspiration was significantly increased in patients. Therefore, the new device may facilitate the assessment of some aspects of swallowing dysfunction. PMID- 27665104 TI - Systemic inflammation is associated with the density of immune cells in the tumor microenvironment of gastric cancer. AB - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and the prognostic nutritional index (PNI) are markers of systemic inflammation known to be useful prognostic indicators of malignancy. However, little evidence has defined the influence of inflammation on the tumor microenvironment. METHODS: Two hundred eighty-eight patients who underwent curative surgery for gastric cancer were included. Preoperative peripheral blood samples were used to analyze the NLR and PNI. The optimal cutoff levels for the NLR and PNI were defined by receiver operating characteristic curve analysis for survival (NLR = 2.7, PNI = 47.7). The densities of specific immune cells (CD3+, CD4+, CD8+) within the tumor microenvironment were measured in tumor microarrays by immunohistochemical analysis. RESULTS: Two hundred thirty-five patients (81.6 %) had a low NLR and 53 patients (18.4 %) had a high NLR. One hundred seventeen patients (40.6 %) had a low PNI and 171 patients (59.4 %) had a high PNI. CD3+ and CD8+ immune cell density were not associated with the NLR and PNI. However, in the high-NLR group compared with the low-NLR group, CD4+ immune cell density was significantly decreased (P < 0.001). Similarly, the density of CD4+ immune cells was also significantly decreased in the low-PNI group compared with the high-PNI group (P = 0.007). A high NLR and a low PNI were correlated with worse overall survival in multivariate analysis (P = 0.028 and P = 0.002 respectively). CONCLUSIONS: The NLR and PNI are associated with the density of CD4+ immune cells in the tumor microenvironment, which leads to prognostic values of systemic inflammation in gastric cancer. PMID- 27665105 TI - Angiotensin-Converting Enzyme Inhibitors and Parameters of Sarcopenia: Relation to Muscle Mass, Strength and Function: Data from the Berlin Aging Study-II (BASE II). AB - BACKGROUND: Pharmacological options for the treatment of sarcopenia currently do not exist. However, off-label treatment options of some established drugs have been suggested. OBJECTIVES: The aim of this study was to assess differences in various muscle and physical performance parameters in relation to the intake of angiotensin-converting enzyme (ACE) inhibitors in a cohort of community-dwelling older people. METHODS: Eight hundred and thirty-eight participants from the Berlin Aging Study-II (BASE-II) were included. Appendicular lean mass was assessed with dual-energy X-ray absorptiometry and related to height and body mass index. Muscle strength was measured by grip strength and related to muscle mass (arm muscle quality) and functional status was assessed via the timed "Up and Go" test. RESULTS: Users of ACE inhibitors had higher lean mass related to height but significantly lower lean mass related to body mass index (p = 0.001 for women and p < 0.0001 for men). Moreover, they exhibited lower arm muscle quality (p = 0.032 for women and p = 0.031 for men) and reported difficulties in climbing stairs more often than non-users (p = 0.014 for women and p = 0.004 for men). After adjustment for confounders, there were no significant differences regarding lean mass, arm muscle quality and the timed "Up and Go" test according to the use of ACE inhibitors. CONCLUSIONS: In BASE-II, no positive relationship was found between the intake of ACE inhibitors and lean mass, strength, muscle quality or function. Moreover, remarkable differences between parameters of absolute and relative lean mass in relation to the use of ACE inhibitors became evident. Fat mass proved to be an important confounder and therefore muscle mass cannot be viewed irrespectively of whole body composition. PMID- 27665106 TI - Phenosafranin inhibits nuclear localization of transglutaminase 2 without affecting its transamidase activity. AB - Transglutaminase 2 (TG2) localizes to the nucleus and induces apoptosis through a crosslinking inactivation of Sp1 in JHH-7 cells treated with acyclic retinoid. We screened an inhibitor suppressing transamidase activity in the nucleus without affecting transamidase activity itself. Phenosafranin was found to inhibit nuclear localization of EGFP-tagged TG2 and dose-dependently reduce nuclear transamidase activity without affecting the activity in a tube. We concluded that phenosafranin was a novel TG2 inhibitor capable of suppressing its nuclear localization. PMID- 27665108 TI - Laser use in direct pulp capping: A meta-analysis. AB - BACKGROUND: The authors of this study evaluated the effects of lasers on the outcome of direct pulp capping by means of a meta-analysis. TYPES OF STUDIES REVIEWED: The authors completed a literature search on PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure, as well as a manual search of the reference lists of all identified articles since the introduction of lasers in endodontics in 1971 through May 30, 2016. The authors systematically evaluated the studies that met the inclusion criteria and performed a meta analysis. RESULTS: The authors selected 5 studies about 4 laser systems (carbon dioxide; diode; erbium,chromium:yttrium-selenium-gallium-garnet; and erbium:yttrium-aluminum-garnet) from the 510 articles to be included in this meta analysis. Using a fixed-effects model, they found no significant heterogeneity between these studies (chi2 = 0.83, P = .99, I2 = 0%). Their results showed that the success rate (89.9%) of the laser groups was higher than that of 67.2% of the control groups, and the difference was statistically significant (risk ratio, 1.35; 95% confidence interval, 1.23-1.49; P < .00001). CONCLUSIONS AND PRACTICAL IMPLICATIONS: On the basis of the limited evidence, the use of lasers effectively improved the prognosis of direct pulp capping treatment for permanent teeth. PMID- 27665107 TI - Leptin as a Mediator of Obesity-Induced Hypertension. AB - Hypertension and associated cardiovascular diseases represent the most common health complication of obesity and the leading cause of morbidity and mortality in overweight and obese patients. Emerging evidence suggests a critical role for the central nervous system particularly the brain action of the adipocyte-derived hormone leptin in linking obesity and hypertension. The preserved ability of leptin to cause cardiovascular sympathetic nerve activation despite the resistance to the metabolic actions of the hormone appears essential in this pathological process. This review describes the evidence supporting the neurogenic bases for obesity-associated hypertension with a particular focus on the neuronal and molecular signaling pathways underlying leptin's effects on sympathetic nerve activity and blood pressure. PMID- 27665111 TI - Design of a Secure Authentication and Key Agreement Scheme Preserving User Privacy Usable in Telecare Medicine Information Systems. AB - Authentication and key agreement schemes play a very important role in enhancing the level of security of telecare medicine information systems (TMISs). Recently, Amin and Biswas demonstrated that the authentication scheme proposed by Giri et al. is vulnerable to off-line password guessing attacks and privileged insider attacks and also does not provide user anonymity. They also proposed an improved authentication scheme, claiming that it resists various security attacks. However, this paper demonstrates that Amin and Biswas's scheme is defenseless against off-line password guessing attacks and replay attacks and also does not provide perfect forward secrecy. This paper also shows that Giri et al.'s scheme not only suffers from the weaknesses pointed out by Amin and Biswas, but it also is vulnerable to replay attacks and does not provide perfect forward secrecy. Moreover, this paper proposes a novel authentication and key agreement scheme to overcome the mentioned weaknesses. Security and performance analyses show that the proposed scheme not only overcomes the mentioned security weaknesses, but also is more efficient than the previous schemes. PMID- 27665112 TI - Semantically Enriched Data Access Policies in eHealth. AB - Internet of Things (IoT) requires novel solutions to facilitate autonomous, though controlled, resource access. Access policies have to facilitate interactions between heterogeneous entities (devices and humans). Here, we focus our attention on access control in eHealth. We propose an approach based on enriching policies, based on well-known and widely-used eXtensible Access Control Markup Language, with semantics. In the paper we describe an implementation of a Policy Information Point integrated with the HL7 Security and Privacy Ontology. PMID- 27665109 TI - Gene expression noise is affected differentially by feedback in burst frequency and burst size. AB - Inside individual cells, expression of genes is stochastic across organisms ranging from bacterial to human cells. A ubiquitous feature of stochastic expression is burst-like synthesis of gene products, which drives considerable intercellular variability in protein levels across an isogenic cell population. One common mechanism by which cells control such stochasticity is negative feedback regulation, where a protein inhibits its own synthesis. For a single gene that is expressed in bursts, negative feedback can affect the burst frequency or the burst size. In order to compare these feedback types, we study a piecewise deterministic model for gene expression of a self-regulating gene. Mathematically tractable steady-state protein distributions are derived and used to compare the noise suppression abilities of the two feedbacks. Results show that in the low noise regime, both feedbacks are similar in term of their noise buffering abilities. Intriguingly, feedback in burst size outperforms the feedback in burst frequency in the high noise regime. Finally, we discuss various regulatory strategies by which cells implement feedback to control burst sizes of expressed proteins at the level of single cells. PMID- 27665110 TI - Characterization and Low-Resolution Structure of an Extremely Thermostable Esterase of Potential Biotechnological Interest from Pyrococcus furiosus. AB - Enzymes isolated from extremophiles often exhibit superior performance and potential industrial applications. There are several advantages performing biocatalysis at elevated temperatures, including enhanced reaction rates, increased substrate solubility and decreased risks of contamination. Furthermore, thermophilic enzymes usually exhibit high resistance against many organic solvents and detergents, and are also more resistant to proteolytic attack. In this study, we subcloned and characterized an esterase from the hyperthermophilic archaeon Pyrococcus furiosus (Pf_Est) that exhibits optimal activity around 80 degrees C using naphthol-derived substrates and p-nitrophenyl palmitate (pNPP). According to the circular dichroism spectra, the secondary structure of P. furiosus esterase, which is predominantly formed by a beta-sheet structure, is very stable, even after incubation at 120 degrees C. We performed SAXS to determine the low-resolution structure of Pf_Est, which is monomeric in solution at 80 degrees C and has a molecular weight of 28 kDa. The Km and V max values for this esterase acting on pNPP were 0.53 mmol/L and 6.5 * 10-3 U, respectively. Pf_Est was most active in the immiscible solvents and retained more than 50 % in miscible solvents. Moreover, Pf_Est possesses transesterification capacity, presenting better results when isobutanol was used as an acyl acceptor (2.69 +/- 0.14 * 10-2 MUmol/min mg) and the highest hydrolytic activity toward olive oil among different types of oils testes in this study. Collectively, these biophysical and catalytic properties are of interest for several biotechnological applications that require harsh conditions, including high temperature and the presence of organic solvents. PMID- 27665113 TI - Hypergraph Based Feature Selection Technique for Medical Diagnosis. AB - The impact of internet and information systems across various domains have resulted in substantial generation of multidimensional datasets. The use of data mining and knowledge discovery techniques to extract the original information contained in the multidimensional datasets play a significant role in the exploitation of complete benefit provided by them. The presence of large number of features in the high dimensional datasets incurs high computational cost in terms of computing power and time. Hence, feature selection technique has been commonly used to build robust machine learning models to select a subset of relevant features which projects the maximal information content of the original dataset. In this paper, a novel Rough Set based K - Helly feature selection technique (RSKHT) which hybridize Rough Set Theory (RST) and K - Helly property of hypergraph representation had been designed to identify the optimal feature subset or reduct for medical diagnostic applications. Experiments carried out using the medical datasets from the UCI repository proves the dominance of the RSKHT over other feature selection techniques with respect to the reduct size, classification accuracy and time complexity. The performance of the RSKHT had been validated using WEKA tool, which shows that RSKHT had been computationally attractive and flexible over massive datasets. PMID- 27665114 TI - Long-Term Follow-Up after Phrenic Nerve Reconstruction for Diaphragmatic Paralysis: A Review of 180 Patients. AB - Background Phrenic nerve reconstruction has been evaluated as a method of restoring functional activity and may be an effective alternative to diaphragm plication. Longer follow-up and a larger cohort for analysis are necessary to confirm the efficacy of this procedure for diaphragmatic paralysis. Methods A total of 180 patients treated with phrenic nerve reconstruction for chronic diaphragmatic paralysis were followed for a median 2.7 years. Assessment parameters included: 36-Item Short Form Health Survey (SF-36) physical functioning survey, spirometry, chest fluoroscopy, electrodiagnostic evaluation, a five-item questionnaire to assess specific functional issues, and overall patient-reported outcome. Results Overall, 134 males and 46 females with an average age of 56 years (range: 10-79 years) were treated. Mean baseline percent predicted values for forced expiratory volume in 1 second, forced vital capacity, vital capacity, and total lung capacity, were 61, 63, 67, and 75%, respectively. The corresponding percent improvements in percent predicted values were: 11, 6, 9, and 13% (p <= 0.01; <= 0.01; <= 0.05; <= 0.01). Mean preoperative SF-36 physical functioning survey scores were 39%, and an improvement to 65% was demonstrated following surgery (p <= 0.0001). Nerve conduction latency, improved by an average 23% (p <= 0.005), and there was a corresponding 125% increase in diaphragm motor amplitude (p <= 0.0001). A total of 89% of patients reported an overall improvement in breathing function. Conclusion Long-term assessment of phrenic nerve reconstruction for diaphragmatic paralysis indicates functional correction and symptomatic relief. PMID- 27665115 TI - Improved kinetic model for the transcutaneous measurement of glomerular filtration rate in experimental animals. AB - Transcutaneous measurement of the glomerular filtration rate (tGFR) is now frequently used in animal studies. tGFR allows consecutive measurements on the same animal, including multiple measurements on a daily basis, because no blood sampling is required. Here we derive and validate a novel kinetic model for the description of transcutaneously measured FITC-Sinistrin excretion kinetics. In contrast to standard 1- to 3-compartment models, our model covers the complete kinetic, including injection and distribution of the tracer in the plasma compartment. Because the model describes the complete progression of the measurement, it allows further refinement by correcting for baseline shifts observed occasionally during measurement. Possible reasons for shifts in the background signal include photo bleaching of the skin, autofluorescence, changes of physiological state of the animals during the measurements, or effects arising from the attachment of the measurement device. Using the new 3-compartment kinetic model with modulated baseline (tGFR3cp.b.m), tGFR measurements in rats can reach comparable precision as those from GFR measurements assessed using a gold standard technique based on constant infusion of a tracer. Moreover, the variability of simultaneous (parallel) measurements, as well as repeated tGFR measurements in the same animals, showed higher precision when tGFR3cp.b.m was compared with the 1-compartment tGFR1cp model. PMID- 27665116 TI - Ultrasound-based imaging methods of the kidney-recent developments. AB - In recent years, several novel ultrasound (US)-based techniques have emerged for kidney diagnostic imaging, including tissue stiffness assessment with elastography, Ultrasensitive Doppler techniques, and contrast-enhanced ultrasonography to assess renal microvascularization. Renal elastography has become available with the development of noninvasive quantitative techniques, following the rapidly growing field of liver fibrosis diagnosis. With the increased incidence of chronic kidney disease, noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application of US elastography from one organ to the other due to anatomic and technical issues. Today, renal elastography appears to be a promising application that, however, still requires optimization and validation. New ultrasensitive Doppler techniques improve the detection of slow blood flow and can be used alone or after administration of US contrast agents. These microbubble-based agents are extremely well tolerated and can be administered even in cases of impaired renal function. Despite the lack of approval, they improve the characterization of atypical renal masses, complex cystic renal masses, and peripheral vascular disorders. Dynamic contrast-enhanced US is based on quantification of the signal intensity from region of interest and mathematical fits of the time-intensity curves. Perfusion-related parameters can be extracted for the monitoring of vascular changes in the renal parenchyma and in tumors in order to evaluate drug response. This estimation of renal perfusion depends on many parameters that should be kept constant for follow-up studies, and, when possible, an internal reference should be used to normalize the measurements. PMID- 27665117 TI - Cocaine and cannabinoids in the atmosphere of Northern Europe cities, comparison with Southern Europe and wastewater analysis. AB - This study reports the first investigation of atmospheric illicit drug concentrations in Northern Europe using measurements of cocaine and cannabinoids in Amsterdam, London and Stockholm. Further, these measurements were compared to those made in Rome to explore the geographical and inter-city variability. Co located measurements of atmospheric particulate mass and PAHs were used to help describe and interpret the illicit drug measurements with respect to atmospheric dispersion. Cocaine concentrations ranged from 0.03 to 0.14ng/m3 in Amsterdam, from 0.02 to 0.33ng/m3 in London and were below quantification limit (3pg/m3) in Stockholm. Cannabinol was the only cannabinoid molecule detected in the three cities. During this campaign, London reported the highest concentrations of cocaine and meaningful differences were detected between the urban background and city centre London sites. Mean cocaine concentrations measured in Amsterdam during March 2011 were also compared with those measured simultaneously in eight Italian cities. The cocaine concentration in Amsterdam was comparable to that measured at an urban background in Milan and at a densely populated site in Florence. Although correlating atmospheric concentrations directly with drug prevalence is not possible using current data, links between concentrations of cocaine and estimates of abuse prevalence assessed by the more routinely used wastewater analysis were also examined. A statistically significant correlation was found between the two sets of data (R2=0.66; p=0.00131). Results confirmed that meteorology, population rate and habits of consumption influence the atmospheric concentrations of drugs. If these confounding factors were better controlled for, the techniques described here could became an easy and cost effective tool to index the impact of cocaine abuse in the area; especially where local hot spots need to be identified. PMID- 27665118 TI - Governance and networks for health co-benefits of climate change mitigation: Lessons from two Indian cities. AB - Health has been the main driver for many urban environmental interventions, particularly in cases of significant health problems linked to poor urban environmental conditions. This paper examines empirically the links between climate change mitigation and health in urban areas, when health is the main driver for improvements. The paper aims to understand how systems of urban governance can enable or prevent the creation of health outcomes via continuous improvements in the environmental conditions in a city. The research draws on cases from two Indian cities where initiatives were undertaken in different sectors: Surat (waste) and Delhi (transportation). Using the literature on network effectiveness as an analytical framework, the paper compares the cases to identify the possible ways to strengthen the governance and policy making process in the urban system so that each intervention can intentionally realize multiple impacts for both local health and climate change mitigation in the long term as well as factors that may pose a threat to long-term progress and revert back to the previous situation after initial achievements. PMID- 27665119 TI - Epigenetic regulation of pro-inflammatory cytokine genes in lipopolysaccharide stimulated peripheral blood mononuclear cells from broilers. AB - Inflammatory response which can be mediated by inflammatory genes, can be induced by pathogenic microorganisms, be associated with enteric diseases and the loss of growth performance in broilers. The understanding of epigenetic regulation of inflammatory genes could help explain the response to infection of microorganisms and inhibit the reaction of inflammation in broilers. This study investigated the effect of histone acetylation by histone deacetylases (HDAC) inhibitors trichostain A (TSA) and DNA methylation by demethylation agent 5-Aza-2' deoxycytidine (AZA) and methyl donor methionine (Met) and folic acid (FA) on the expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) from healthy broilers. The results showed that the mRNA expression of IL-1beta, IL-6 and TNF-alpha can be down regulated by pre-treatment of TSA in LPS-stimulated broiler PBMC. The expression of pro-inflammatory cytokines related with the expression of HDAC7 and HDAC10 which can influence histone acetylation, and may also be affected by increasing the acetylation of non-histone proteins. The demethylation by AZA increased the expression of IL-6 and TNF-alpha in LPS-stimulated broiler PBMC. The addition of FA and Met decreased the expression of DNA methyltransferases (DNMT)1 and DNMT3a, while the Met also down-regulated the expression of IL-6 and TNF-alpha in LPS stimulated cells. In addition, the Met administration increased the methylation of -191 CpG site (up-stream from transcription start site) of IL-6 and -419 CpG site of TNF-alpha. This study indicated that the expression of pro-inflammatory cytokines is regulated by protein acetylation. Demethylation also increased the expression of IL-6 and TNF-alpha, which can be regulated by Met through increasing the promoter methylation. These results may have implications for controlling inflammation by epigenetic regulation in broilers. PMID- 27665120 TI - Algal growth and utilization of phosphorus studied by combined mono-culture and co-culture experiments. AB - Phosphorus (P) plays a critical role in algal growth; therefore, a better understanding of P availability is essential to control harmful algal blooms. Three algae species, Microcystis aeruginosa, Chlorella pyrenoidosa, and Pseudokirchneriella subcapitata, were mono-cultured and co-cultured on three types of P substrates, dissolved inorganic P (DIP), phosphomonoesters glucose-6 phosphate (G-6-P) and beta-glycerol phosphate (beta-glycerol-P), and phosphonate (glyphosate), to explore their growth and P utilization. All three species could utilize dissolved organic P (DOP) to sustain their growth, whereas DIP was their preferred P substrate in both culture types. Algae could regulate the P uptake capacity under different P conditions, and the added P could be rapidly accumulated at the beginning of the culture and slowly utilized during the subsequent life cycle. M. aeruginosa exhibited wider P selectivity and could utilize all three P substrates, whereas the other two species could only use phosphomonoester (G-6-P and beta-glycerol-P) in the mono-cultures. However, in the co-cultures, the relative bioavailability of DOP for M. aeruginosa and C. pyrenoidosa was enhanced, and M. aeruginosa might contribute to the growth of C. pyrenoidosa and P. subcapitata when fed with glyphosate. The three species showed an intrinsic ability to produce alkaline phosphatase (AP), and AP activity (APA) was regulated by Pi stress. However, high APA did not necessarily lead to high Pi release and algal growth on unfavorable substrates. Although M. aeruginosa was not superior in growth rate in the mono-cultures, it showed a better P accumulation ability and maintained stable growth on different P substrates. Moreover, it was a good competitor, suppressing the thriving growth of the other species in co-cultures. Overall, the findings indicated the strategic flexibility of P utilization by algae and the strong competitive ability of M. aeruginosa in Pi-limited and DOP-enriched natural waters. PMID- 27665121 TI - The potential ecological risk of multiwall carbon nanotubes was modified by the radicals resulted from peroxidase-mediated tetrabromobisphenol A reactions. AB - Extensive studies have been conducted on the environmental degradation of multiwall carbon nanotubes (MWCNTs), but primarily focused on the extent and rate of MWCNTs mineralization. Few studies have explored possible structural changes that may occur to MWCNTs during natural or engineered processes. We systematically examined MWCNTs in oxidative coupling reactions in the presence of a common contaminant tetrabromobisphenol A (TBBPA). MWCNTs was modified by the radicals of TBBPA resulting from peroxidase-mediated coupling reaction. Interactions between TBBPA radicals and MWCNTs were definitely confirmed by analyzing the characteristic mass spectrometry response of bromine in TBBPA and the structures of MWCNTs. After reaction with TBBPA radicals for 60 min, the content of bromine contained in MWCNTs was 6.84(+/-0.12)%, a quantity equivalent to a 501.65(+/-2.19) mg loading of TBBPA per gram MWCNTs. Modified MWCNTs had better stability and smaller sizes than that of MWCNTs and TBBPA-adsorbed MWCNTs. Assessment using zebrafish embryos revealed that the modified MWCNTs passed through the chorion and entered the embryo inducing acute toxicity, while the MWCNTs/TBBPA-adsorbed MWCNTs was trapped by chorion. These findings indicated that MWCNTs was modified in peroxidase-mediated coupling reactions, and suggested that such modifications may have an influence on the ecological risks of MWCNTs. PMID- 27665122 TI - Whole exome sequencing identifies a homozygous nonsense variation in ALMS1 gene in a patient with syndromic obesity. AB - In the present study we report on genetic analysis in a patient with developmental delay, truncal obesity and vision problem, to find the causative mutation. Whole exome sequencing was performed on genomic DNA extracted from whole blood of the patient which revealed a homozygous nonsense variant (c.2816T>A) in exon 8 of ALMS1 gene that results in a stop codon and premature truncation at codon 939 (p.L939Ter) of the protein. The mutation was confirmed by Sanger sequencing. Exome sequencing was helpful in establishing diagnosis of Alstrom syndrome in this patient. This case highlights the utility of exome sequencing in clinical practice. PMID- 27665123 TI - Amelanotic iris melanoma. PMID- 27665124 TI - From science to action: Principles for undertaking environmental research that enables knowledge exchange and evidence-based decision-making. AB - Effective conservation requires knowledge exchange among scientists and decision makers to enable learning and support evidence-based decision-making. Efforts to improve knowledge exchange have been hindered by a paucity of empirically grounded guidance to help scientists and practitioners design and implement research programs that actively facilitate knowledge exchange. To address this, we evaluated the Ningaloo Research Program (NRP), which was designed to generate new scientific knowledge to support evidence-based decisions about the management of the Ningaloo Marine Park in north-western Australia. Specifically, we evaluated (1) outcomes of the NRP, including the extent to which new knowledge informed management decisions; (2) the barriers that prevented knowledge exchange among scientists and managers; (3) the key requirements for improving knowledge exchange processes in the future; and (4) the core capacities that are required to support knowledge exchange processes. While the NRP generated expansive and multidisciplinary science outputs directly relevant to the management of the Ningaloo Marine Park, decision-makers are largely unaware of this knowledge and little has been integrated into decision-making processes. A range of barriers prevented efficient and effective knowledge exchange among scientists and decision-makers including cultural differences among the groups, institutional barriers within decision-making agencies, scientific outputs that were not translated for decision-makers and poor alignment between research design and actual knowledge needs. We identify a set of principles to be implemented routinely as part of any applied research program, including; (i) stakeholder mapping prior to the commencement of research programs to identify all stakeholders, (ii) research questions to be co-developed with stakeholders, (iii) implementation of participatory research approaches, (iv) use of a knowledge broker, and (v) tailored knowledge management systems. Finally, we articulate the individual, institutional and financial capacities that must be developed to underpin successful knowledge exchange strategies. PMID- 27665125 TI - Selection of native plants with phytoremediation potential for highly contaminated Mediterranean soil restoration: Tools for a non-destructive and integrative approach. AB - The aim of this study was to develop an effective and non-destructive method for the selection of native Mediterranean plants with phytoremediation potential based on their spontaneous recovery capacities. The study site consisted in a mixed contaminated soils (As, Cu, Pb, Sb, Zn) in the vicinity of a former lead smelting factory abandoned since 1925 in the Calanques National Park (Marseille, southeastern France). We developed an integrated characterization approach that takes into account topsoil metal(loid)s (MM) contamination, plant community composition and structure and mesologic parameters without using destructive methods. From a statistical selection of significant environmental descriptors, plant communities were described and interpreted as the result of spontaneous recovery under multiple stresses and local conditions (both natural and anthropogenic). We collected phytoecological and MM topsoil data using field monitoring and geographic information system (GIS) on a pollution hotspot where natural plant communities occur. The results of the multivariate analysis performed between species and descriptors indicated that a century of MM pollution pressure produced a significant correlation with plant community dynamics in terms of composition, diversity and structure, leading to the co occurrence of different plant succession stages. Thus, these successions seemed linked to the variability of anthropogenic disturbance regimes within the study site. We recorded high topsoil contamination heterogeneity at the scale both of the plot and of the whole study area that suggested a heterogeneous MM distribution pattern dependent on the source of contaminants and site environmental variability. We identified 4 spontaneous plant communities co occurring through a MM contamination gradient that could be used later from degraded to reference communities to define ecological restoration target combined to phytoremediation applications with respect to local conditions. Our results suggested that some of the native plant species such as Coronilla juncea and Globularia alypum might be tolerant to high mixed MM soil concentrations and they could thus be used for phytostabilization purposes in polluted Mediterranean areas in regard to their life-traits. Our non-destructive methodology led both to the selection of tolerant native plant species and communities and identification of highly polluted priority intervention areas through the study site where phytostabilization should be implemented. Furthermore, by analyzing succession dynamics linked to contamination patterns throughout the area and spontaneous recovery of native tolerant vegetation, our methodology opens up broad perspectives and research fields for ecological restoration for Mediterranean protected and contaminated areas based on ecosystem trajectories and new approaches for the integrative management of polluted soils. PMID- 27665126 TI - Pre-invasion economic assessment of invasive species prevention: A putative ambrosia beetle in Southeastern loblolly pine forests. AB - Invasive wood borers vectoring pathogenic fungi have nearly exterminated several North American tree species, and it is unclear whether landscape dominant trees, such as pines, will face similar threats in the future. This paper explores the economic impacts of a hypothetical arrival of a destructive ambrosia beetle "X" (Coleoptera: Curculionidae) that infests loblolly pine (Pinus taeda L.) forests in the Southeastern United States. We develop an economic framework for pre invasion assessment that incorporates fluctuating economic and environmental conditions for a representative loblolly pine stand and biological assumptions from the ongoing laurel wilt epidemic. Assuming an initial annual probability of arrival of a pine infesting ambrosia beetle to be between 0.04 and 0.07, we determine that, on average, the timber economic benefits for a forest landowner are $5325.3 ha-1, with a harvest time of 17.8 years. Our results indicate that an increase in enforcement consistent with an international phytosanitary standard that partially prevents the arrival of ambrosia beetles (30% arrival reduction) would have a strong, positive impact for forest landowners. On average, economic revenues increase to $6116.4 ha-1 and the harvest age is extended to 19 years. On average, the economic losses for forest landowners with no control of ambrosia beetle X would be $791 ha-1, with a harvest time reduction of 1.2 years. The upper-bound regional cost savings from pine-dominated forestry would be roughly $4.6 billion dollars if invasion preventative measures are in place. These benefits vastly outweigh the cost of programs that reduce the expected arrival of exotic ambrosia beetles. PMID- 27665127 TI - Global and Targeted Proteomics of Prostate Cancer Cell Secretome: Combination of 2-Dimensional Image-Converted Analysis of Liquid Chromatography and Mass Spectrometry and In Silico Selection Selected Reaction Monitoring Analysis. AB - Prostate-specific antigen is currently the only protein biomarker routinely used as a diagnostic tool for early detection and treatment monitoring of prostate cancer. However, it remains questionable whether prostate-specific antigen-based screening can sensitively and selectively identify the presence and progression status of primary and metastatic prostate cancers. Hence, the purpose of this study was to identify potential biomarker candidates in the secretome of primary and metastatic prostate cancer cells by using a combination of global and targeted proteomics. Quantitative comparisons among secretome proteins derived from androgen-responsive primary cancer cells (P-22Rv1), androgen-irresponsive bone metastatic cancer cells (M-PC-3), and noncancerous prostate cells (N-PNT2) were performed using 2-dimensional image-converted analysis of liquid chromatography and mass spectrometry followed by in silico selection selected reaction monitoring analysis. Mediator of RNA polymerase II transcription subunit 13-like, insulin-like growth factor-binding protein 2, and hepatocyte growth factor were identified as highly secreted proteins from P-22Rv1 cells compared with N-PNT2 cells. Prostate-associated microseminoprotein, proactivator polypeptide, collagen-alpha-1 (VI) chain, and neuropilin-1 were identified as predominantly secreted proteins in M-PC-3 cells compared with N-PNT2 cells. These proteins in biological fluids are considered to be candidate biomarkers of primary and/or metastatic prostate cancer. PMID- 27665128 TI - Single-step Coprocessing of Cohesive Powder via Mechanical Dry Coating for Direct Tablet Compression. AB - This study aims at testing the feasibility of a single-step coating process to produce a powder formulation of active and inactive ingredients for direct compression. A cohesive ibuprofen powder was coprocessed with a coating material, a binder (polyvinylpyrrolidone K25), and a superdisintegrant (crospovidone). Magnesium stearate (MgSt), l-leucine, and silica were selected as coating materials (1% w/w). A coprocessed powder without any coating material was employed as a control. Coating with MgSt, l-leucine, or silica produced significantly improved powder flow in comparison to the control batch. Robust tablets were produced from the processed powders for each coating material. The tablets compacted using the coated powders with MgSt or l-leucine also exhibited significantly lower tablet ejection forces than the control batch, demonstrating their lubrication effect. Furthermore, the disintegration time and dissolution rates of these tablets made of the formulations coprocessed with lubricants were enhanced, even for those coated with the hydrophobic material such as MgSt that has been previously reported to inhibit dissolution. However, the tablets made with silica-coated powders would not disintegrate. This study indicated the feasibility of a single-step dry coating process to produce powders with both flow-aid and lubrication effects, which are suitable for direct compression. PMID- 27665129 TI - Mitigating Cocrystal Physical Stability Liabilities in Preclinical Formulations. AB - Poor aqueous solubility of a majority of new small molecule chemical entities is a significant challenge in drug discovery since considerably high exposures are often required to enable pharmacokinetic, pharmacology, and toxicology studies. Pharmaceutical cocrystals have received considerable attention in recent years owing to their potential to improve the physicochemical properties and in vivo performance of poorly soluble drugs. However, physical instability in supersaturated solution/suspension formulations is a major concern for their use in preclinical studies. This review will present an overview of the thermodynamic and kinetic contributions impacting physical stability of cocrystals in preclinical formulations with a focus on the role of surfactants, polymeric excipients, and pH. Finally, the in vivo performance of cocrystals will be discussed. The article will conclude with a perspective on strategies to develop physically stable preclinical cocrystal formulations. PMID- 27665130 TI - Associations between milk protein concentration at various stages of lactation and reproductive performance in dairy cows. AB - Milk protein concentration has been positively associated with a range of measures of reproductive performance in dairy cows. These beneficial associations are most likely due to factors affecting both milk protein concentration and reproductive performance possibly being mediated, in part, by energy balance during early lactation. However, it is likely that factors other than energy balance are also involved in these relationships. A retrospective single cohort study was conducted using subsets of data collected from 74 dairy herds with seasonal or split calving patterns. Associations between milk protein concentration at various stages of lactation and reproductive performance in Holstein dairy cows were assessed using random effects logistic regression and survival analysis with milk protein concentration during the cow's breeding period fitted as a time-varying covariate. The beneficial associations between milk protein concentration and each of the 4 selected indices for measuring reproductive performance were evident when milk protein concentration was derived for each 30-d period from calving up to 300d in milk. For the first 150d of lactation the adjusted odds ratios were highest from 31 to 60d and only slightly lower for all periods up to 150d of lactation. Estimated associations for 31 to 60d were stronger than for 0 to 30d. In addition, milk protein concentration during a cow's breeding period was positively associated with the subsequent daily hazard of conception, even after adjusting for milk protein concentration in the cow's first or second month of lactation. Milk protein concentrations from 0 to 30d of lactation were less closely correlated with concentrations measured at subsequent 30-d intervals; correlations were closer between other periods in lactation. These results indicate that the association between milk protein concentration and reproductive performance is partly due to factors other than the extent of negative energy balance in early lactation. However, it is possible that energy balance accounts for some of the relationship as the magnitude and direction of energy balance can vary within and between cows throughout lactation. Factors determining milk protein concentration during the first 30d of lactation are not identical to the causes of milk protein concentration later in lactation, and some of the latter causes of milk protein concentration may be more closely related to the underlying mechanisms contributing to the milk protein concentration-reproductive performance relationship. Milk protein concentrations from a single test day from any day of lactation predict subpopulations of cows with differing average reproductive performance; milk protein concentrations measured after 30d of lactation are more useful than concentrations measured in the first 30d for identifying these subpopulations. Further research is required to identify the causes of these associations. PMID- 27665131 TI - Associations between milk protein concentration, milk yield, and reproductive performance in dairy cows. AB - Milk protein concentration in dairy cows has been positively associated with a range of measures of reproductive performance. It was possible that these associations were due to confounding by milk volume. A retrospective single cohort study was conducted using data collected from 74 dairy herds with seasonal or split calving patterns. Associations between milk protein concentration and reproductive performance in Holstein dairy cows were assessed using random effects logistic regression. The key finding from this study was that the associations between milk protein concentration in early lactation and reproductive performance were not due to confounding by milk yield. Associations between milk protein concentration and reproductive performance were weaker at higher early lactation milk yields, but positive associations were evident at all milk volumes assessed. The second major finding was that increases in milk yield were associated with improved proportions of cows pregnant by wk 6 and 21 at low to moderate milk protein concentrations but with decreases in these reproductive measures at high milk protein concentrations. Thus, no simple relationship is present between milk yield and reproductive performance; effects of milk yield depend on milk protein concentration. These results indicate that mechanisms causing the associations between milk protein concentration and reproductive performance may be linked to milk yield but these mechanisms operate over a wide range of milk yields (<2,000 to >=5,000kg in the first 120d of lactation). Further research is required to identify the causes of these associations. PMID- 27665132 TI - Multivariate factor analysis of detailed milk fatty acid profile: Effects of dairy system, feeding, herd, parity, and stage of lactation. AB - We investigated the potential of using multivariate factor analysis to extract metabolic information from data on the quantity and quality of milk produced under different management systems. We collected data from individual milk samples taken from 1,158 Brown Swiss cows farmed in 85 traditional or modern herds in Trento Province (Italy). Factor analysis was carried out on 47 individual fatty acids, milk yield, and 5 compositional milk traits (fat, protein, casein, and lactose contents, somatic cell score). According to a previous study on multivariate factor analysis, a variable was considered to be associated with a specific factor if the absolute value of its correlation with the factor was >=0.60. The extracted factors were representative of the following 12 groups of fatty acids or functions: de novo fatty acids, branched fatty acid milk yield, biohydrogenation, long-chain fatty acids, desaturation, short-chain fatty acids, milk protein and fat contents, odd fatty acids, conjugated linoleic acids, linoleic acid, udder health, and vaccelenic acid. Only 5 fatty acids showed small correlations with these groups. Factor analysis suggested the existence of differences in the metabolic pathways for de novo short- and medium chain fatty acids and Delta9-desaturase products. An ANOVA of factor scores highlighted significant effects of the dairy farming system (traditional or modern), season, herd/date, parity, and days in milk. Factor behavior across levels of fixed factors was consistent with current knowledge. For example, compared with cows farmed in modern herds, those in traditional herds had higher scores for branched fatty acids, which were inversely associated with milk yield; primiparous cows had lower scores than older cows for de novo fatty acids, probably due to a larger contribution of lipids mobilized from body depots on milk fat yield. The statistical approach allowed us to reduce a large number of variables to a few latent factors with biological meaning and able to represent groups of fatty acids with a common origin and function. Multivariate factor analysis would therefore be a valuable tool for studying the influence of different production environments and individual animal factors on milk fatty acid composition, and for developing nutritional strategies able to manipulate the milk fatty acid profile according to consumer demand. PMID- 27665133 TI - Retention payoff-based cost per day open regression equations: Application in a user-friendly decision support tool for investment analysis of automated estrus detection technologies. AB - Assessing the economic implications of investing in automated estrus detection (AED) technologies can be overwhelming for dairy producers. The objectives of this study were to develop new regression equations for estimating the cost per day open (DO) and to apply the results to create a user-friendly, partial budget, decision support tool for investment analysis of AED technologies. In the resulting decision support tool, the end user can adjust herd-specific inputs regarding general management, current reproductive management strategies, and the proposed AED system. Outputs include expected DO, reproductive cull rate, net present value, and payback period for the proposed AED system. Utility of the decision support tool was demonstrated with an example dairy herd created using data from DairyMetrics (Dairy Records Management Systems, Raleigh, NC), Food and Agricultural Policy Research Institute (Columbia, MO), and published literature. Resulting herd size, rolling herd average milk production, milk price, and feed cost were 323 cows, 10,758kg, $0.41/kg, and $0.20/kg of dry matter, respectively. Automated estrus detection technologies with 2 levels of initial system cost (low: $5,000 vs. high: $10,000), tag price (low: $50 vs. high: $100), and estrus detection rate (low: 60% vs. high: 80%) were compared over a 7-yr investment period. Four scenarios were considered in a demonstration of the investment analysis tool: (1) a herd using 100% visual observation for estrus detection before adopting 100% AED, (2) a herd using 100% visual observation before adopting 75% AED and 25% visual observation, (3) a herd using 100% timed artificial insemination (TAI) before adopting 100% AED, and (4) a herd using 100% TAI before adopting 75% AED and 25% TAI. Net present value in scenarios 1 and 2 was always positive, indicating a positive investment situation. Net present value in scenarios 3 and 4 was always positive in combinations using a $50 tag price, and in scenario 4, the $5,000, $100, and 80% combination. Overall, the payback period ranged from 1.6 yr to greater than 10 yr. Investment analysis demonstration results were highly dependent on assumptions, especially AED system initial investment and labor costs. Dairy producers can use herd-specific inputs with the cost per day open regression equations and the decision support tool to estimate individual herd results. PMID- 27665134 TI - Influence of raw milk quality on processed dairy products: How do raw milk quality test results relate to product quality and yield? AB - This article provides an overview of the influence of raw milk quality on the quality of processed dairy products and offers a perspective on the merits of investing in quality. Dairy farmers are frequently offered monetary premium incentives to provide high-quality milk to processors. These incentives are most often based on raw milk somatic cell and bacteria count levels well below the regulatory public health-based limits. Justification for these incentive payments can be based on improved processed product quality and manufacturing efficiencies that provide the processor with a return on their investment for high-quality raw milk. In some cases, this return on investment is difficult to measure. Raw milks with high levels of somatic cells and bacteria are associated with increased enzyme activity that can result in product defects. Use of raw milk with somatic cell counts >100,000cells/mL has been shown to reduce cheese yields, and higher levels, generally >400,000 cells/mL, have been associated with textural and flavor defects in cheese and other products. Although most research indicates that fairly high total bacteria counts (>1,000,000 cfu/mL) in raw milk are needed to cause defects in most processed dairy products, receiving high-quality milk from the farm allows some flexibility for handling raw milk, which can increase efficiencies and reduce the risk of raw milk reaching bacterial levels of concern. Monitoring total bacterial numbers in regard to raw milk quality is imperative, but determining levels of specific types of bacteria present has gained increasing importance. For example, spores of certain spore-forming bacteria present in raw milk at very low levels (e.g., <1/mL) can survive pasteurization and grow in milk and cheese products to levels that result in defects. With the exception of meeting product specifications often required for milk powders, testing for specific spore-forming groups is currently not used in quality incentive programs in the United States but is used in other countries (e.g., the Netherlands). PMID- 27665135 TI - Short communication: Relationship between serum cortisol concentration and defensive behavioral responses of dairy cows exposed to natural infestation by stable fly, Stomoxys calcitrans. AB - The aim of this study was conducted to evaluate the effect of natural infestation by Stomoxys calcitrans on the behavioral and adrenocortical responses of dairy cattle. Twenty Holstein cows randomly selected were individually sprayed with insecticide once every 7d, whereas no insecticide was applied to the other 20 animals. The average number of flies per cow was estimated daily, and the frequency of fly-avoidance behaviors was measured daily; plasma cortisol concentration was measured each morning. No flies were ever counted on the treated cows at any time during the experiment, whereas an average of 17.13+/ 1.14 (+/-standard error) flies/d were recorded on untreated cows. Tail movement was the most frequent behavior displayed, with stamps or kicks showing the highest increment rate (41.2*) when fly population increased from zero to greater than 51 flies/cow. Cortisol concentration increased to a maximum of 56.81+/ 39.53ng/mL with 26 to 30 flies/cow per day. Coefficients of determination between the number of flies, cortisol concentration, tail movements, and stamps or kicks were 0.73, 0.78, and 0.81, respectively. The multiple correlation coefficient was 0.90, with 81% of the variation in cortisol concentration explainable by variation in the number of flies per cow and the frequency of fly-avoidance behaviors. It was concluded that plasma cortisol concentration is linearly related to a combination of the number of flies and the frequency of fly dislodging behaviors, producing a maximum response before reaching maximum fly loads. PMID- 27665136 TI - Is reticular temperature a useful indicator of heat stress in dairy cattle? AB - The present study investigated whether reticular temperature (RT) in dairy cattle is a useful indicator of heat stress considering the effects of milk yield and water intake (WI). In total, 28 Holstein-Friesian dairy cows raised on 3 farms in Lower Saxony, Germany, were studied from March to December 2013. During the study, RT and barn climate parameters (air temperature, relative humidity) were measured continuously and individual milk yield was recorded daily. Both the daily temperature-humidity index (THI) and the daily median RT per cow were calculated. Additionally, the individual WI (amount and frequency) of 10 cows during 100d of the study was recorded on 1 farm. Averaged over all farms, daily THI ranged between 35.4 and 78.9 with a mean (+/-standard deviation) of 60.2 (+/ 8.7). Dairy cows were on average (+/-standard deviation) 110.9d in milk (+/-79.3) with a mean (+/-standard deviation) milk yield of 35.2kg/d (+/-9.1). The RT was affected by THI, milk yield, days in milk, and WI. Up to a THI threshold of 65, RT remained constant at 39.2 degrees C. Above this threshold, RT increased to 39.3 degrees C and further to 39.4 degrees C when THI >=70. The correlation between THI >=70 and RT was 0.22, whereas the coefficient ranged between r=-0.08 to +0.06 when THI <70. With increasing milk yield, RT decreased slightly from 39.3 degrees C (<30kg/d) to 39.2 degrees C (>=40kg/d). For daily milk yields of >=40kg, the median RT and daily milk yield were correlated at r=-0.18. The RT was greater when dairy cows yielded >=30kg/d and THI >=70 (39.5 degrees C) compared with milk yields <30kg and THI <70 (39.3 degrees C). The WI, which averaged (+/ standard deviation) 11.5 l (+/-5.7) per drinking bout, caused a mean decrease in RT of 3.2 degrees C and was affected by the amount of WI (r=0.60). After WI, it took up to 2h until RT reached the initial level before drinking. In conclusion, RT increased when the THI threshold of 65 was exceeded. A further increase was noted when THI >=70. Nevertheless, the effects of WI and milk yield have to be considered carefully when RT is used to detect hyperthermia in dairy cattle. PMID- 27665137 TI - Practices for the disbudding and dehorning of dairy calves by veterinarians and dairy producers in Ontario, Canada. AB - Disbudding and dehorning dairy calves is very common, despite the introduction of polled genetics to most dairy breeds. Appropriate pain-control practices for these procedures affect both calf welfare and public perception of the dairy industry. Previously published work has shown that North American dairy producers have not widely adopted use of these medications for disbudding or dehorning. However, since the last published work examining these practices in Canada, changes regarding awareness, availability, and future requirements for pain control have occurred in the industry. With this in mind, online and telephone surveys of both veterinarians (n=238) and dairy producers (n=603) in Ontario, Canada, were conducted in the fall of 2014 with a goal of describing current disbudding and dehorning practices and examining factors associated with the adoption of pain control use. Approximately three-quarters of dairy producers reported performing disbudding or dehorning themselves, whereas the remainder used a veterinarian or technician. Almost all (97%) of the veterinarians surveyed reported using local anesthetic, 62% used sedation, and 48% used a nonsteroidal anti-inflammatory drug. Producer use of local anesthetic was 62%, 38% used sedation and 24% used a nonsteroidal anti-inflammatory drug. Seventy-eight percent of veterinarian disbudding or dehorning was done before 8wk of age, whereas 64% of dairy producers performed this procedure before 8wk of age. Seventy-two percent of veterinarians and 63% of producers reported changing their disbudding or dehorning practices over the past 10 yr; of producers that changed their practices, 73% cited their herd veterinarian as influential. The use of pain control described in these surveys is higher than previously reported in Ontario. Identification of factors associated with best practices, or the lack of adoption of these practices, may help veterinarians target appropriate educational opportunities for their dairy clients. PMID- 27665138 TI - Cheesemaking in highland pastures: Milk technological properties, cream, cheese and ricotta yields, milk nutrients recovery, and products composition. AB - Summer transhumance of dairy cows to high Alpine pastures is still practiced in many mountainous areas. It is important for many permanent dairy farms because the use of highland pastures increases milk production and high-priced typical local dairy products often boost farm income. As traditional cheese- and ricotta making procedures in Alpine pastures are central to this dairy system, the objective of this study was to characterize the quality and efficiency of products and their relationships with the quality and availability of grass during the grazing season. The milk from 148 cows from 12 permanent farms reared on a temporary farm located in Alpine pastures was processed every 2wk during the summer (7 cheesemakings from late June to early September). During each processing, 11 dairy products (4 types of milk, 2 by-products, 3 fresh products, and 2 ripened cheeses) were sampled and analyzed. In addition, 8 samples of fresh forage from the pasture used by the cows were collected and analyzed. At the beginning of the pasture season the cows were at 233+/-90d in milk, 2.4+/-1.7 parities, and produced 23.6+/-5.7kg/d of milk. The milk yield decreased with the move from permanent to temporary farms and during the entire summer transhumance, but partly recovered after the cows returned to the permanent farms. Similar trends were observed for the daily yields of fat, protein, casein, lactose, and energy, as we found no large variations in the quality of the milk, with the exception of the first period of Alpine pasture. The somatic cell counts of milk increased during transhumance, but this resulted from a concentration of cells in a lower quantity of milk rather than an increase in the total number of cells ejected daily from the udder. We noted a quadratic trend in availability of forage (fresh and dry matter weight per hectare), with a maximum in late July. The quality of forage also varied during the summer with a worsening of chemical composition. The evening milk (before and after natural creaming), the whole morning milk, and the mixed vat milk had different chemical compositions, traditional coagulation properties, and curd-firming modeling parameters. These variations over the pasture season were similar to the residual variations with respect to chemical composition, and much lower with respect to coagulation and curd-firming traits. Much larger variations were noted in cream, cheese, and ricotta yields, as well as in nutrient recoveries in curd during the pasture season. The protein content of forage was correlated with some of the coagulation and curd-firming traits, the ether extract of forage was positively correlated with milk fat content and cheese yields, and fiber fractions of forage were unfavorably correlated with some of the chemical and technological traits. Traditional cheese- and ricotta-making procedures showed average cream, cheese, and ricotta yields of 6.3, 14.2, and 4.9%, respectively, and an overall recovery of almost 100% of milk fat, 88% of milk protein, and 60% of total milk solids. PMID- 27665139 TI - Factors affecting milking speed in Murciano-Granadina breed goats. AB - Milk flow during the first minute of milking was analyzed using data from 1,132 Murciano-Granadina breed goats belonging to 17 herds. During the individual lactations, 2 test days were scheduled for recording several milk flow traits, total milk, milk composition (fat and protein percentages), and somatic cell count. Average lag time from teatcup attachment to arrival of milk at the milk claw (T0) was 4.9 s and at the milk meter (T1) was 15.8 s. Average milk flow after 30 s (MF0.5) was 0.29kg/30 s (0 to 1.1kg/30 s) and milk flow at 60 s or milking speed (MF1) was 0.67kg/min (0.1 to 2.1kg/min). Repeatabilities of T0, T1, MF0.5, and MF1 were 0.45, 0.58, 0.62, and 0.68, respectively. The MF1 showed high phenotypic correlation withT1(-0.63) and MF0.5 (0.90), medium values withT0( 0.42) and total milk (0.22), and very low values (-0.04 to -0.12) with fat, protein, and somatic cell count. We found no differences between flows during the first 3 lactations, with a reduction as the lactation number increased. Months in milk since parturition affected MF1, being highest in the first 3mo (0.67 0.71kg/min) and decreasing until the end of lactation (0.58kg/min). The effect of herd-test day was significant for all traits. Inclusion of all these effects for the analysis of milk flow traits is considered necessary. PMID- 27665140 TI - A correlation consistency based multivariate alarm thresholds optimization approach. AB - Different alarm thresholds could generate different alarm data, resulting in different correlations. A new multivariate alarm thresholds optimization methodology based on the correlation consistency between process data and alarm data is proposed in this paper. The interpretative structural modeling is adopted to select the key variables. For the key variables, the correlation coefficients of process data are calculated by the Pearson correlation analysis, while the correlation coefficients of alarm data are calculated by kernel density estimation. To ensure the correlation consistency, the objective function is established as the sum of the absolute differences between these two types of correlations. The optimal thresholds are obtained using particle swarm optimization algorithm. Case study of Tennessee Eastman process is given to demonstrate the effectiveness of proposed method. PMID- 27665141 TI - Ultrasonic bone localization algorithm based on time-series cumulative kurtosis. AB - The design and optimization of protective equipment and devices such as exoskeletons and prosthetics have the potential to be enhanced by the ability of accurately measure the positions of the bones during movement. Existing technologies allow a quite precise measurement of motion-mainly by using coordinate video-cameras and skin-mounted markers-but fail in directly measuring the bone position. Alternative approaches, as fluoroscopy, are too invasive and not usable during extended lapses of time, either for cost or radiation exposure. An approach to solve the problem is to combine the skin-glued markers with ultrasound technology in order to obtain the bone position by measuring at the same time the marker coordinates in 3D space and the depth of the echo from the bone. Given the complex structure of the bones and the tissues, the echoes from the ultrasound transducer show a quite complex structure as well. To reach a good accuracy in determining the depth of the bones, it is of paramount importance the ability to measure the time-of-flight (TOF) of the pulse with a high level of confidence. In this paper, the performance of several methods for determining the TOF of the ultrasound pulse has been evaluated when they are applied to the problem of measuring the bone depth. Experiments have been made using both simple setups used for calibration purposes and in real human tissues to test the performance of the algorithms. The results show that the method used to process the data to evaluate the time-of-flight of the echo signal can significantly affect the value of the depth measurement, especially in the cases when the verticality of the sensor with respect to the surface causing the main echo cannot be guaranteed. Finally, after testing several methods and processing algorithms for both accuracy and repeatability, the proposed cumulative kurtosis algorithm was found to be the most appropriate in the case of measuring bone depths in vivo with ultrasound sensors at frequencies around 5MHz. PMID- 27665142 TI - Adaptive integral LOS path following for an unmanned airship with uncertainties based on robust RBFNN backstepping. AB - This paper investigates the path following control problem for an unmanned airship in the presence of unknown wind and uncertainties. The backstepping technique augmented by a robust adaptive radial basis function neural network (RBFNN) is employed as the main control framework. Based on the horizontal dynamic model of the airship, an improved adaptive integral line-of-sight (LOS) guidance law is first proposed, which suits any parametric paths. The guidance law calculates the desired yaw angle and estimates the wind. Then the controller is extended to cope with the airship yaw tracking and velocity control by resorting to the augmented backstepping technique. The uncertainties of the dynamics are compensated by using the robust RBFNNs. Each robust RBFNN utilizes an nth-order smooth switching function to combine a conventional RBFNN with a robust control. The conventional RBFNN dominates in the neural active region, while the robust control retrieves the transient outside the active region, so that the stability range can be widened. Stability analysis shows that the controlled closed-loop system is globally uniformly ultimately bounded. Simulations are provided to validate the effectiveness of the proposed control approach. PMID- 27665143 TI - Extended observer based on adaptive second order sliding mode control for a fixed wing UAV. AB - This paper addresses the design of attitude and airspeed controllers for a fixed wing unmanned aerial vehicle. An adaptive second order sliding mode control is proposed for improving performance under different operating conditions and is robust in presence of external disturbances. Moreover, this control does not require the knowledge of disturbance bounds and avoids overestimation of the control gains. Furthermore, in order to implement this controller, an extended observer is designed to estimate unmeasurable states as well as external disturbances. Additionally, sufficient conditions are given to guarantee the closed-loop stability of the observer based control. Finally, using a full 6 degree of freedom model, simulation results are obtained where the performance of the proposed method is compared against active disturbance rejection based on sliding mode control. PMID- 27665144 TI - Output feedback control for a class of nonlinear systems with actuator degradation and sensor noise. AB - This paper investigates the output feedback control problem of a class of nonlinear systems with sensor noise and actuator degradation. Firstly, by using the descriptor observer approach, the origin system is transformed into a descriptor system. On the basis of the descriptor system, a novel Proportional Derivative (PD) observer is developed to asymptotically estimate sensor noise and system state simultaneously. Then, by designing an adaptive law to estimate the effectiveness of actuator, an adaptive observer-based controller is constructed to ensure that system state can be regulated to the origin asymptotically. Finally, the design scheme is applied to address a flexible joint robot link problem. PMID- 27665145 TI - Development of a low cost test rig for standalone WECS subject to electrical faults. AB - In this paper, a contribution to the development of low-cost wind turbine (WT) test rig for stator fault diagnosis of wind turbine generator is proposed. The test rig is developed using a 2.5kW, 1750 RPM DC motor coupled to a 1.5kW, 1500 RPM self-excited induction generator interfaced with a WT mathematical model in LabVIEW. The performance of the test rig is benchmarked with already proven wind turbine test rigs. In order to detect the stator faults using non-stationary signals in self-excited induction generator, an online fault diagnostic technique of DWT-based multi-resolution analysis is proposed. It has been experimentally proven that for varying wind conditions wavelet decomposition allows good differentiation between faulty and healthy conditions leading to an effective diagnostic procedure for wind turbine condition monitoring. PMID- 27665147 TI - Bioactive composites containing TEGDMA-functionalized calcium phosphate particles: Degree of conversion, fracture strength and ion release evaluation. AB - OBJECTIVE: To evaluate the strength and ion release of experimental composites containing TEGDMA-functionalized calcium phosphate particles. METHODS: Seven composites containing equal parts (in mols) of BisGMA and TEGDMA and 60vol% of fillers were manipulated. Filler phase was constituted by silanized barium glass and 0% (control), 10% or 20% (volume) of dicalcium phosphate dihydrate (DPCD) particles, either non-functionalized or functionalized with two different TEDGMA contents. DCPD particles were synthesized and characterized by X-ray diffraction (XRD), elemental analysis, surface area and dynamic light scattering. Composites were tested for degree of conversion (DC) by near-FTIR. Biaxial flexural strength (BFS) was determined after 24h and 28days in water. Calcium and phosphate release after 7days was assessed using inductively coupled plasma optical emission spectrometry (ICP-OES). Data were analyzed by ANOVA/Tukey test (alpha:5%). RESULTS: XRD confirmed the crystalline structure corresponding to DCPD. Elemental analysis revealed particles with zero, 14% or 22% TEGDMA, with similar D50 (around 19MUm) and surface areas from 3.5 to 11.4m2/g. The presence of DCPD did not reduce DC. After 24h, functionalization (both 14% and 22% TEGDMA) improved composite strength in comparison to non-functionalized DCPD, both at 10% and 20% levels. After 28days, BFS of materials containing 10% functionalized DCPD were statistically similar to the control containing only barium glass. Among composites containing 10% DCPD, particle functionalization with 14% TEGDMA did not jeopardize ion release. SIGNIFICANCE: At 10vol%, the use of TEGDMA functionalized CaP particles improved composite strength in relation to non functionalized particles, while maintaining similar ion release levels. PMID- 27665146 TI - Influence of nanogel additive hydrophilicity on dental adhesive mechanical performance and dentin bonding. AB - OBJECTIVE: To assess the influence of hydrophilicity of reactive nanogels on the mechanical performance of dental adhesives and microtensile bond strength (MUTBS) to dentin after 24h or 3 months of aging. METHODS: A series of three nanogels were synthesized: NG1-IBMA/UDMA; NG2-HEMA/BisGMA; NG3-HEMA/TE-EGDMA. The nanogels were dispersed in solvent, HEMA or BisGMA/HEMA. The degree of conversion (DC) of the materials was measured and the flexural modulus of these polymers was evaluated in dry or wet conditions. For MUTBS analysis, a model adhesive was used without nanogel (control) or with the incorporation of nanogels. MUTBS was evaluated after storage in distilled water for 24h or 3 months. The analysis of the fracture was performed after MUTBS testing. Data were analyzed using ANOVA and Tukey's test (alpha=0.05). RESULTS: Water significantly increased the modulus of NG1 and NG2 dispersed in solvent, while significantly decreased the stiffness of NG3. All polymers dispersed in HEMA and BisGMA/HEMA had significantly lower modulus when stored in water. NG2 showed the highest DC in solvent and BisGMA/HEMA. In HEMA, NG1 and NG3 produced the highest DC. After three months, NG2 showed the best MUTBS. The MUTBS of NG2-containing adhesive resin significantly increased after 3 months, while storage had no effect in the control group, NG1 and NG3. SIGNIFICANCE: The more hydrophobic IBMA/UDMA nanogel showed higher bulk material mechanical property results, but the best dentin bond strength values, and notably strength values that improved upon storage, were obtained with the amphiphilic nanogel based on BisGMA/HEMA. PMID- 27665148 TI - Screening for lung cancer: Does MRI have a role? AB - While the inauguration of national low dose computed tomographic (LDCT) lung cancer screening programs has started in the USA, other countries remain undecided, awaiting the results of ongoing trials. The continuous technical development achieved by stronger gradients, parallel imaging and shorter echo time has made lung magnetic resonance imaging (MRI) an interesting alternative to CT. For the detection of solid lesions with lung MRI, experimental and clinical studies have shown a threshold size of 3-4mm for nodules, with detection rates of 60-90% for lesions of 5-8mm and close to 100% for lesions of 8mm or larger. From experimental work, the sensitivity for infiltrative, non-solid lesions would be expected to be similarly high as that for solid lesions, but the published data for the MRI detection of lepidic growth type adenocarcinoma is sparse. Moreover, biological features such as a longer T2 time of lung cancer tissue, tissue compliance and a more rapid uptake of contrast material compared to granulomatous diseases, in principle should allow for the multi-parametric characterization of lung pathology. Experience with the clinical use of lung MRI is growing. There are now standardized protocols which are easy to implement on current scanner hardware configurations. The image quality has become more robust and currently ongoing studies will help to further contribute experience with multi-center, multi-vendor and multi-platform implementation of this technology. All of the required prerequisites have now been achieved to allow for a dedicated prospective large scale MRI based lung cancer screening trial to investigate the outcomes from using MRI rather than CT for lung cancer screening. This is driven by the hypothesis that MRI would reach a similarly high sensitivity for the detection of early lung cancer with fewer false positive exams (better specificity) than LDCT. The purpose of this review article is to discuss the potential role of lung MRI for the early detection of lung cancer from a technical point of view and to discuss a few of the possible scenarios for lung cancer screening implementation using this imaging modality. There is little doubt that MRI could play a significant role in lung cancer screening, but how and when will depend on the threshold needed for positive screens (e.g. lesion volume and required diagnostic accuracy), cost-effectiveness and improved patient outcomes from a reduction in the need to follow up benign nodules. Potential applications range from lung MRI as the first choice screening modality to the role of an ad hoc on site test for the detailed evaluation of a subgroup of positive screening results. PMID- 27665149 TI - Spirostanol glycosides with hemostatic and antimicrobial activities from Trillium kamtschaticum. AB - Ten spirostanol glycosides, trillikamtosides A-J, together with eleven known analogues, were isolated from the hemostatic fraction of the 75% aqueous EtOH extract of the whole herbs of Trillium kamtschaticum. Their structures were established by extensive spectroscopic data analysis and chemical methods. The aglycones of three of these compounds had unique 3beta,17alpha-dihydroxy spirostanes featuring a double bond between C-4 and C-5, while two others represent a rare class of spirostanol glycosides which possess a 5(6 -> 7) abeo steroidal aglycone. All the compounds were evaluated for their hemostatic and antimicrobial activities. Three of the spirostanol glycosides exhibited induced platelet aggregation at a concentration of 300 MUg/mL with maximal induced platelet aggregation rates of 72%, 71%, and 62% in rabbits, respectively, and their EC50 values were 492.7, 203.3, and 109.8 MUM. Five of the spirostanol glycosides showed an anti-Candida albicans effect with MIC values of 21.1, 10.6, 8.8, 21.6, and 11.0 MUM, respectively. PMID- 27665151 TI - [Epidemiology: Data from France and USA]. AB - Epidemiological data on the incidence, the survival and the prognostic factors of cardiac arrest (CA) are often heterogeneous. However, recent advances in methodology and research have improved the knowledge on that topic. The generation of registries in United States and France, in particular, improved significantly the characterization and the transatlantic comparability of provided data. The main information of these registries confirmed the high incidence of cardiac arrest and highlighted an overall survival better than previous published. The assessment of characteristics of patients and pre- and in hospital interventions supports the consistent influence of identified prognostic factors in United States and France as well. Advantages of these registries rely on the development of large database and quality of information. However, some data are limited by volunteering collection, incompletion and/or restriction on defined communities, avoiding any generalization. Nevertheless, these collections of data represent an outstanding resource for descriptive and analytic interpretation of outcome in cardiac arrest setting. They also represent a necessary source for origin of randomized clinical trials, representing solely the high level of evidence for application of management strategy. PMID- 27665150 TI - Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat. AB - BACKGROUND: Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies. OBJECTIVES: To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching. SETTING: University laboratories. METHODS: Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12. RESULTS: Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration. CONCLUSION: Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery. PMID- 27665152 TI - Intimate Partner Violence Perpetration Among Adolescent Males in Disadvantaged Neighborhoods Globally. AB - PURPOSE: Intimate partner violence (IPV) affects one in three women globally, with adolescent and young adult women at highest risk. Less is known about IPV perpetration. We compare the prevalence and correlates of IPV perpetration among 15- to 19-year-old adolescent males in Baltimore (United States), Johannesburg (South Africa), Delhi (India), and Shanghai (China). METHODS: A cross-sectional survey was conducted in 2013 with males aged 15-19 recruited via respondent driven sampling from disadvantaged neighborhoods in four cities: Baltimore (United States), New Delhi (India), Johannesburg (South Africa), and Shanghai (China); total n = 751 ever-partnered men. We describe the prevalence of past year physical and sexual IPV perpetration and evaluate associations with gender norm attitudes, mental health, substance use, victimization experiences, and demographic factors. RESULTS: Past-year physical or sexual IPV perpetration ranged from 9% in Shanghai to 40% in Johannesburg. Factors associated with past year perpetration across multiple sites included: binge drinking (Johannesburg adjusted odds ratio [AOR] = 2.8, Baltimore AOR = 6.7, and Shanghai AOR = 3.2), depressive symptoms (Johannesburg AOR = 2.4 and Shanghai AOR = 2.2), victimization in the home (Baltimore AOR = 2.5, Shanghai AOR = 2.7, and Johannesburg AOR = 1.7), and community violence victimization (Baltimore AOR = 7.0, Delhi AOR = 4.1, and Johannesburg AOR = 2.8). Equitable gender norm attitudes were protective against IPV perpetration in Johannesburg and Shanghai. Demographic factors (e.g., age, employment, and education) were inconsistently associated with IPV perpetration across sites. CONCLUSIONS: Past-year IPV perpetration was prevalent with differences identified across settings. Findings suggest the need to scale up evidence-based interventions targeting adolescents in disadvantaged urban communities in order to address many modifiable factors associated with IPV perpetration in this study. PMID- 27665153 TI - Long-Acting Reversible Contraception Counseling and Use for Older Adolescents and Nulliparous Women. AB - PURPOSE: The majority of pregnancies during adolescence are unintended, and few adolescents use long-acting reversible contraception (LARC) due in part to health care providers' misconceptions about nulliparous women's eligibility for the intrauterine device. We examined differences in LARC counseling, selection, and initiation by age and parity in a study with a provider's LARC training intervention. METHODS: Sexually active women aged 18-25 years receiving contraceptive counseling (n = 1,500) were enrolled at 20 interventions and 20 control clinics and followed for 12 months. We assessed LARC counseling and selection, by age and parity, with generalized estimated equations with robust standard errors. We assessed LARC use over 1 year with Cox proportional hazards models with shared frailty for clustering. RESULTS: Women in the intervention had increased LARC counseling, selection, and initiation, with similar effects among older adolescent and nulliparous women, and among young adult and parous women. Across study arms, older adolescents were as likely as young adults to receive LARC counseling (adjusted odds ratio [aOR] = .85; 95% confidence interval [CI]: .63-1.15), select LARC (aOR = .86; 95% CI: .64-1.17), and use LARC methods (adjusted hazard ratio [aHR] = .94; 95% CI: .69-1.27). Nulliparous women were less likely to receive counseling (aOR = .57; 95% CI: .42-.79) and to select LARC (aOR = .53; 95% CI: .37-.75) than parous women, and they initiated LARC methods at lower rates (aHR = .65; 95% CI: .48-.90). Nulliparous women had similar rates of implant initiation but lower rates of intrauterine device initiation (aHR = .59; 95% CI: .41-.85). CONCLUSIONS: Continued efforts should be made to improve counseling and access to LARC methods for nulliparous women of all ages. PMID- 27665154 TI - The effect of ambient exposure to PM2.5 on the transfusion usage of blood components and adverse transfusion reactions in the haze weather. AB - BACKGROUND: Accumulating evidence has shown that ambient exposure to PM2.5, especially in the haze weather, increased the risk of various diseases. However, the association of air pollution status with blood transfusion utilization and the prevalence and severity of adverse transfusion reactions remain to be clarified. MATERIALS AND METHODS: The data of monthly transfusion usage of blood components, adverse transfusion reactions, as well as PM2.5 and PM10 levels from 2013 to 2015 were obtained. RESULTS: During the study interval, both PM2.5 and PM10 levels were significantly increased in the haze weather when compared with the non-haze weather. The utilization of total blood components per patient-month in the haze weather was prone to be increased when compared with that in the non haze weather (13.28 +/- 1.66 vs. 12.33 +/- 1.30, p = 0.068). The usage of RBC products per patient-month in the haze weather was significantly increased when compared with that in the non-haze weather (4.39 +/- 0.39 vs. 4.07 +/- 0.30, p = 0.009). There was no obvious difference between the haze and non-haze weathers for the usage of platelet and plasma products per patient-month. Besides, no definite differences of the prevalence and severity of transfusion-associated adverse reaction were observed between the haze and non-haze weathers. CONCLUSION: Our study first indicated that transfusion utilization, particularly the RBC products, was significantly increased in the haze weather when compared with that in the non-haze weather. There was no obvious association of air pollution with the prevalence and severity of adverse transfusion reactions and further research is required. PMID- 27665155 TI - Factors affecting the CD34+ cell yields from the second donations of healthy donors: The steady-state lymphocyte count is a good predictive factor. AB - BACKGROUND: A second allogeneic hematopoietic stem-cell transplantation and donor lymphocyte infusion using cells from the same donor is a therapeutic option in the case of stem-cell graft failure or disease relapse, but little is known about the factors associated with the CD34+ cell yields from second donations. METHODS: One-hundred healthy donors who underwent a second mobilization treatment and peripheral blood stem-cell (PBSC) collection were studied. For both mobilization processes, 5 ug of granulocyte colony-stimulating factor per kg per day was administered. The blood counts of the donors were monitored during the processes. RESULTS: The second donations from the same donors provided lower apheresis yields than did the initial collections. The number of CD34+ cells collected from normal donors after a second cycle of PBSC mobilization was associated with their steady-state lymphocyte counts and the intertransplantation interval. Female sex negatively affected the CD34+ cell yields. The cutoff value for the steady-state absolute lymphocyte count was 2.055 * 109/L. CONCLUSION: To harvest greater numbers of CD34+ cells from second collections, male donors and those with intervals of longer than 9 months between donations should be selected. The lymphocyte counts prior to the first donations may predict the content of CD34+ cells in the allografts prepared using the second donations. PMID- 27665156 TI - Blood transfusion service in disasters. PMID- 27665157 TI - Coronary Artery Calcium: Need for More Clarity in Guidelines. PMID- 27665158 TI - Impact of Longitudinal Lesion Geometry on Location of Plaque Rupture and Clinical Presentations. AB - OBJECTIVES: This study sought to investigate the impact of longitudinal lesion geometry on the location of plaque rupture and clinical presentation and its mechanism. BACKGROUND: The relationships among lesion geometry, external hemodynamic forces acting on the plaque, location of plaque rupture, and clinical presentation have not been comprehensively investigated. METHODS: This study enrolled 125 patients with plaque rupture documented by intravascular ultrasound. Longitudinal locations of plaque rupture were identified and categorized by intravascular ultrasound. Patients' clinical presentations and TIMI (Thrombolysis In Myocardial Infarction) flow grade in an initial angiogram were compared according to the location of plaque rupture. Longitudinal lesion asymmetry was quantitatively assessed by the luminal radius change over the segment length (radius gradient [RG]). Lesions with a steeper radius change in the upstream segment compared with the downstream segment (RGupstream > RGdownstream) were defined as upstream-dominant lesions. RESULTS: On the basis of the site of maximum rupture aperture, 56.0%, 16.0%, and 28.0% of the patients had upstream, minimal lumen area, and downstream rupture, respectively. Patients with upstream rupture more frequently presented with ST-segment elevation myocardial infarction (45.7%, 40.0%, 22.9%; p = 0.030) and with TIMI flow grade <3 (32.9%, 20.0%, 17.1%; p = 0.042). According to the ratio of upstream and downstream RG, 69.5% of lesions were classified as upstream-dominant lesions, and 30.5% were classified as downstream-dominant lesions. Among the 66 upstream-dominant lesions, 65 cases (98.5%) had upstream rupture, and the RG ratio (RGupstream/RGdownstream) was an independent predictor of upstream rupture (odds ratio: 1.481; 95% confidence interval: 1.035 to 2.120; p = 0.032). Upstream-dominant lesions more frequently manifested with ST-segment elevation myocardial infarction than did downstream dominant lesions (48.5% vs. 24.1%; p = 0.026). CONCLUSIONS: Both clinical presentation and degree of flow limitation were associated with the location of plaque rupture. Longitudinal lesion asymmetry assessed by RG, which can affect regional distribution of hemodynamic stress, was associated with the location of rupture and with clinical presentation. PMID- 27665159 TI - Screening CT Angiography of the Aorta, Visceral Branch Vessels, and Pelvic Arteries in Fibromuscular Dysplasia. AB - OBJECTIVES: This study sought to evaluate the diagnostic yield of a dedicated computed tomography angiography (CTA) protocol of the chest, abdomen, and pelvis in patients with fibromuscular dysplasia (FMD). BACKGROUND: FMD is an uncommon vascular disease that may result in stenosis, dissection, or aneurysm of nearly all arterial distributions, typically affecting medium-sized arteries. Findings from the United States Registry for Fibromuscular Dysplasia have suggested the potential need to perform screening imaging of the aorta and medium branch vessels. METHODS: A total of 113 consecutive patients enrolled in our institutional FMD registry who received a tailored CTA protocol at our institution between March 2013 and June 2015 were included in this study. Arterial phase contrast-enhanced images were obtained on a dual-source scanner using high pitch and electrocardiogram trigger. Images were analyzed by 2 readers. RESULTS: Abnormalities including beading, aneurysm, dissection, and stenosis/occlusion were noted in aortic, renal, mesenteric, and iliac distributions. The most commonly affected vessels were the renal arteries (n = 76 [67%]), followed by the lower extremity/iliac arteries (n = 37 [32%]). Aortic abnormalities were less frequently encountered (n = 3 [3%]), including 1 case with mild dilation (4.2 cm) of the ascending aorta and 2 cases of dissection involving the descending aorta, 1 with mild dilation (4.4 cm). Incremental findings beyond those known at patient intake were commonly noted, including new areas of arterial beading (n = 55 [49%]), new aneurysms (n = 21 [19%]), and new dissections (n = 3 [3%]). Reformatted images were crucial, affecting final assessment in 56% of cases evaluated by reader 1 and 36% evaluated by reader 2. CONCLUSIONS: Screening chest, abdomen, and pelvis CTA in patients with FMD showed substantial and incremental diagnostic yield. Reformatted images should routinely be included in imaging analysis. Abnormalities in the aorta were not common, so screening of the thoracic aorta may not be indicated. PMID- 27665161 TI - Asymmetric Longitudinal Lesion Geometry: Expanding Clinical Applications of Biomechanics. PMID- 27665160 TI - Clinical Utility of Longitudinal Strain to Predict Functional Recovery in Patients With Tachyarrhythmia and Reduced LVEF. AB - OBJECTIVES: This study sought to assess the time course of presumptive tachycardia-induced cardiomyopathy and the predictors of left ventricular (LV) functional recovery in such patients. BACKGROUND: Tachycardia-induced cardiomyopathy is a potentially reversible cardiomyopathy with effective treatment of the tachyarrhythmia. However, cases without improvement of LV systolic function were found occasionally. The diagnosis of tachycardia-induced cardiomyopathy can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited. METHODS: LV segmental longitudinal strains (LS) were evaluated by 2-dimensional speckle tracking in 71 consecutive patients (65 +/- 16 years; 61% men) with tachyarrhythmia and reduced left ventricular ejection fraction (LVEF) without any other known cardiovascular disease, and 30 age and sex-matched control subjects. Relative apical LS ratio (RALSR) was defined using the equation: average apical LS / (average basal LS + average mid LS) as a marker of strain distribution. RESULTS: Compared with control subjects, patients with tachyarrhythmia had significantly lower global LS. Improvement in LVEF within 6 months after treatment of index arrhythmia was observed in 41 patients, and LVEF did not improve in 30 patients. In univariate analysis, lower LVEF at baseline (hazard ratio: 0.59 per 1 SD; p = 0.04) and higher RALSR (hazard ratio: 11.2 per 1 SD; p < 0.001) were associated with no recovery in LVEF during follow-up. In a multivariate logistic regression model, the significant predictor of LV systolic functional recovery was RALSR (hazard ratio: 22.9 per 1 SD; p = 0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88). CONCLUSIONS: The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF. PMID- 27665162 TI - Fibromuscular Dysplasia: Looking Beyond the "String of Beads". PMID- 27665164 TI - Myocardium at Risk by Early Gadolinium Enhancement MR Imaging: A Moving Target? PMID- 27665163 TI - CAC Score Improves Coronary and CV Risk Assessment Above Statin Indication by ESC and AHA/ACC Primary Prevention Guidelines. AB - OBJECTIVES: The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. BACKGROUND: Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. METHODS: In 3,745 subjects (59 +/- 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. RESULTS: The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (<100) was common in subjects with statin indication by both guidelines (59% for ESC, 62% for AHA/ACC). During 10.4 +/- 2.0 years of follow-up, 131 myocardial infarctions occurred. For ESC recommendations, CAC score differentiated risk for subjects without (1.0 [95% confidence interval (CI): 0.4 to 1.5] vs. 6.5 [95% CI: 4.1 to 8.9] coronary events per 1,000 person years for CAC 0 vs. >=100) and with statin indication (2.6 [95% CI: 0.6 to 4.7] vs. 9.9 [95% CI: 7.3 to 12.5] per 1,000 person-years for CAC 0 vs. >=100). Likewise, CAC score stratified proportions experiencing events subjects with statin indication according to AHA/ACC (2.7 [95% CI: 1.1 to 4.2] vs. 9.1 [95% CI: 7.0 to 11.0] per 1,000 person-years for CAC 0 vs. >=100), whereas event rate in subjects without statin indication was low (1.1 [95% CI: 0.65 to 1.68] per 1,000 person-years). CONCLUSIONS: Current ESC and AHA/ACC guidelines lead to markedly different recommendation regarding statin therapy in a German primary prevention cohort. Quantification of CAC score in addition to the guidelines improves stratification between subjects at high versus low risk for coronary events, indicating that CAC scoring may help to match intensified risk factor modification to atherosclerotic plaque burden as well as actual risk while avoiding therapy in subjects with low coronary atherosclerosis that have low 10 year event rate. PMID- 27665166 TI - Myocardial Strain in the Identification of Tachycardia-Induced Cardiomyopathy: Unscrambling the Egg. PMID- 27665165 TI - Early Gadolinium Enhancement for Determination of Area at Risk: A Preclinical Validation Study. AB - OBJECTIVES: The aim of this study was to determine whether early gadolinium enhancement (EGE) by cardiac magnetic resonance (CMR) in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis. BACKGROUND: It remains controversial whether only the irreversibly injured myocardium enhances when CMR is performed in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction because it correlates well with T2-weighted imaging of the AAR, but this still requires pathological validation. METHODS: Eleven dogs underwent 2 h of coronary artery occlusion and 48 h of reperfusion before imaging at 1.5-T. EGE imaging was performed 3 min after contrast administration with coverage of the entire left ventricle. Late gadolinium enhancement imaging was performed between 10 and 15 min after contrast injection. AAR was defined as myocardium with blood flow <2 SD from remote myocardium determined by microspheres during occlusion. The size of infarction was determined with triphenyltetrazolium chloride. RESULTS: There was no significant difference in the size of enhancement by EGE compared with the size of AAR by microspheres (44.1 +/- 15.8% vs. 42.7 +/- 9.2%; p = 0.61), with good correlation (r = 0.88; p < 0.001) and good agreement by Bland-Altman analysis (mean bias 1.4 +/- 17.4%). There was no difference in the size of enhancement by EGE compared with enhancement on native T1 and T2 maps. The size of EGE was significantly greater than the infarct by triphenyltetrazolium chloride (44.1 +/- 15.8% vs. 20.7 +/- 14.4%; p < 0.001) and late gadolinium enhancement (44.1 +/- 15.8% vs. 23.5 +/- 12.7%; p < 0.001). CONCLUSIONS: At 3 min post-contrast, EGE correlated well with the AAR by microspheres and CMR and was greater than infarct size. Thus, EGE enhances both reversibly and irreversibly injured myocardium. PMID- 27665167 TI - Surface plasmon resonance as a tool for investigation of non-covalent nanoparticle interactions in heterogeneous self-assembly & disassembly systems. AB - Biomolecule-driven assembly of nanoparticles is a powerful and convenient approach for development of advanced nanosensors and theranostic agents with diverse "on-demand" composition and functionality. While a lot of research is being devoted to fabrication of such agents, the development of non-invasive analytical tools to monitor self-assembly/disassembly processes in real-time substantially lags behind. Here, we demonstrate the capabilities of localized surface plasmon resonance (SPR) phenomenon to study non-covalent interactions not just between plasmonic particles, but between gold nanoparticles (AuNP) and non plasmonic ones. We show its potential to investigate assembly and performance of a novel type of advanced smart materials, namely, biocomputing agents. These agents, self-assembled from nanoparticles via biomolecular interfaces such as proteins, DNA, etc., can analyze presence of biomolecular inputs according to Boolean logic and undergo the input-induced disassembly in order to implement the proper output action. Using UV-Vis spectroscopy to monitor the assembly/disassembly processes of the basic YES-gate structure that consists of a polymer core particle with a multitude of associated gold nanoparticles, we found that the structure transformations are well-characterized by pronounced difference in SPR spectral band position (shifting up to 50nm). This SPR shift correlates remarkably well with biochemical estimation of the assembly/disassembly extent, and can provide valuable real-time kinetic analysis. We believe that the obtained data can be easily extended to other non-plasmonic nanoparticle systems having similar chemical and colloidal properties. SPR method can become a valuable addition to analytical toolbox for characterization of self assembled smart nanosystems used in biosensing, imaging, controlled release and other applications. PMID- 27665168 TI - Tailoring gas sensor arrays via the design of short peptides sequences as binding elements. AB - A semi-combinatorial virtual approach was used to prepare peptide-based gas sensors with binding properties towards five different chemical classes (alcohols, aldehydes, esters, hydrocarbons and ketones). Molecular docking simulations were conducted for a complete tripeptide library (8000 elements) versus 58 volatile compounds belonging to those five chemical classes. By maximizing the differences between chemical classes, a subset of 120 tripeptides was extracted and used as scaffolds for generating a combinatorial library of 7912 tetrapeptides. This library was processed in an analogous way to the former. Five tetrapeptides (IHRI, KSDS, LGFD, TGKF and WHVS) were chosen depending on their virtual affinity and cross-reactivity for the experimental step. The five peptides were covalently bound to gold nanoparticles by adding a terminal cysteine to each tetrapeptide and deposited onto 20MHz quartz crystal microbalances to construct the gas sensors. The behavior of peptides after this chemical modification was simulated at the pH range used in the immobilization step. DeltaF signals analyzed by principal component analysis matched the virtually screened data. The array was able to clearly discriminate the 13 volatile compounds tested based on their hydrophobicity and hydrophilicity molecules as well as the molecular weight. PMID- 27665169 TI - Impedimetric immunosensor for the label-free and direct detection of botulinum neurotoxin serotype A using Au nanoparticles/graphene-chitosan composite. AB - In this work, a novel nanocomposite film consisting of the Au nanoparticles/graphene-chitosan has been designed to construct an impedimetric immunosensor for a rapid and sensitive immunoassay of botulinum neurotoxin A (BoNT/A). BoNT/A antibody was immobilized on glassy carbon electrode modified with Au nanoparticles/graphene-chitosan for the signal amplification. The fabrication of immunosensor was extensively characterized by using transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The impedance changes, due to the specific immuno-interactions at the immunosensor surface that efficiently restricted the electron transfer of redox probe Fe(CN)64 /3- were utilized to detect BoNT/A. The measurements were highly targeted specific and linear with logarithmic BoNT/A concentrations in PBS, milk and human serum across a 0.27-268pgmL-1 range and associated with a detection limit of 0.11pgmL-1. PMID- 27665170 TI - Amyloidogenesis of the amylin analogue pramlintide. AB - Amylin is a pancreatic peptide hormone co-secreted along with insulin by the beta cells. It is found in amyloid deposits in both type 2 diabetic individuals and elder non-diabetic. The triple proline amylinomimetic compound (25,28,29-Pro human amylin) named pramlintide was designed aiming to solve the solubility and amyloid characteristics of human amylin. We have found by using ion mobility spectrometry-based mass spectrometry that pramlintide is able to assembly into multimers. Pramlintide formed amyloid fibrils in vitro in a pH-dependent kinetic process within a few hours, as followed by thioflavin T, quantification of soluble peptide and further characterized by transmission electron microscopy, atomic force microscopy and X-ray diffraction. These data indicate that pramlintide can form amyloid fibers. PMID- 27665172 TI - The combination of systemic inflammation-based marker NLR and circulating regulatory T cells predicts the prognosis of resectable pancreatic cancer patients. AB - BACKGROUND: The systemic inflammation response and immune impairment are closely related to the development and progression of various tumours, such as pancreatic cancer. In this study, we evaluated circulating inflammation factors and circulating regulatory T cells (Tregs) as markers of immunosuppression in a cohort of Chinese patients with resectable pancreatic cancer. METHODS: Samples were retrospectively collected from a series of 195 pathological stage I/II pancreatic cancer patients who underwent potentially curative surgery between June 2010 and April 2014. To examine the prognostic factors, circulating systemic inflammation-based markers and Tregs, detected by flow cytometry, were analysed. RESULTS: Univariate analyses revealed that the neutrophil-lymphocyte ratio (NLR), TNM stage, differentiation, chemotherapy, CA19-9 levels and presence of Tregs are significantly associated with overall survival in patients with resectable pancreatic cancers. NLR (p = 0.001, HR = 0.538), TNM stage (p = 0.004, HR = 0.593), differentiation (p = 0.011, HR = 0.46), chemotherapy (p = 0.006, HR = 0.516) and Tregs (p = 0.001, HR = 0.558) are identified as independent prognostic markers by multivariate analyses. Interestingly, we also found that high NLR levels combined with a high proportion of Tregs (p < 0.001, HR = 3.521) correlate strongly with worse survival, with a greater than 3.5-fold increased risk of death compared with those with concurrent low levels of NLR and Tregs. CONCLUSIONS: The preoperative NLR and circulating regulatory T cells are potentially independent prognostic factors for overall survival in resectable pancreatic cancer patients. High NLR levels combined with poor immune state before surgery, as measured by Tregs, are associated with an extremely poor prognosis. PMID- 27665171 TI - Effect of routine prenatal supplementation on vitamin concentrations in maternal serum and breast milk. AB - OBJECTIVE: The aim of the present study was to assess the effect of multivitamin supplements and their different vitamin A sources on retinol concentrations in serum and colostrum milk of postpartum women. METHODS: This was a retrospective cross-sectional study composed of healthy postpartum women attending two Brazilian private maternity wards (N = 100). According to the type of multivitamin taken during pregnancy, the women were assigned to one of four groups: control group (CG; n = 25), formulation 1 (F1; n = 25), formulation 2 (F2; n = 25), and formulation 3 (F3; n = 25). Blood and colostrum samples were collected under fasting conditions and retinol was analyzed by high-performance liquid chromatography. Dietary vitamin A was assessed using a food frequency questionnaire. Retinol concentrations <20 MUg/dL (<0.70 MUmol/L) in serum and <60 MUg/dL (2.10 MUmol/L) in colostrum were considered indicative of vitamin A deficiency. RESULTS: Of women in the control group, 12% (n = 3) presented serum retinol levels below the cut-off value for adequacy; this was not observed in the supplemented groups. Evaluating the retinol content in breast milk, supplemented groups F1 and F3 presented 4% (n = 1) of inadequacy cases, whereas F2 presented 40% (n = 10). The concentrations found in the F2 and F3 groups were statistically different (P < 0.05). CONCLUSIONS: The use of multivitamin supplements containing vitamin A during pregnancy prevents vitamin A deficiency regardless of the source administered. In breast milk, supplementation with beta-carotene provided a lower concentration of vitamin A compared with retinol. PMID- 27665174 TI - The Cahn-Hilliard phase separation principle maybe the tip of an iceberg: Comment on "Phase separation driven by density-dependent movement: A novel mechanism for ecological patterns" by Q.-X. Liu et al. PMID- 27665173 TI - Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma. AB - BACKGROUND: Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+ M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA+-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis. METHODS: In this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA+-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA+-M2BP, we investigated the presence of WFA+-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53). The bio-physiological effects of MDA-PATC53 supernatant were evaluated. Finally, the difference in the expression of glycosylation enzymes between MDA-PATC53 and Panc-1 were analyzed by cDNA microarray. RESULTS: We found that the serum WFA+-M2BP level could distinguish the 2 groups. The median serum COI of WFA+-M2BP was 0.98 and 0.51 in PDAC and CP, respectively. Additionally, WFA+-M2BP positive PDACs were more frequently associated with metastatic lesions than the WFA+-M2BP negative PDACs (91.6% vs. 41.7%, P = 0.009). The MDA-PATC53 cells alone produced WFA+-M2BP. However, we found that MDA-PATC53 supernatant containing WFA+-M2BP (1.0 COI) did not alter the biological behavior of cancer cell lines. The results of cDNA microarray revealed that several glycosylation enzymes with pro-oncologic function were highly expressed in MDA-PATC53 compared to Panc-1. CONCLUSIONS: Serum WFA+-M2BP can be a useful biomarker for the diagnosis of PDAC and the prediction of disease progression since it potentially reflects altered pro oncologic glycosylation enzymes. PMID- 27665175 TI - The spreading of infectious diseases in modern socio-technical systems Comment on "Pattern transitions in spatial epidemics: Mechanisms and emergent properties" by Gui-Quan Sun et al. PMID- 27665177 TI - Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of alpha,beta-tubulin polymerization. AB - We have discovered O6-benzyl glaziovianin A, which showed stronger inhibition of microtubule polymerization (IC50=2.1MUM) than known alpha,beta-tubulin inhibitors, such as colchicine and glaziovianin A. Also, we performed competition binding experiments of O6-benzyl glaziovianin A and revealed that O6-benzyl glaziovianin A binds to the colchicine binding site with high affinity. It is interesting that glaziovianin A derivatives change their mode of action in benzylation at the O6 (alpha,beta-tubulin inhibitor) or O7 (gamma-tubulin specific inhibitor) position. PMID- 27665176 TI - Crohn's disease-associated mucosal factors regulate the expression of TNF-like cytokine 1A and its receptors in primary subepithelial intestinal myofibroblasts and intestinal epithelial cells. AB - Intestinal subepithelial myofibroblasts (SEMFs) exert a profibrotic role in Crohn's disease (CD). Tumor necrosis factor-like cytokine 1A (TL1A) and its receptors, death-domain receptor 3 (DR3) and decoy receptor 3 (DcR3), are mucosal factors with significant involvement in experimental inflammation and CD. We aimed to determine the regulation of expression of this system of proteins in SEMFs and intestinal epithelial cells. The relative amount of mRNA transcripts for TL1A, DR3, and DcR3 was measured by real-time reverse transcription polymerase chain reaction in cultured primary SEMFs, colonic myofibroblast cell line 18CO, and epithelial cell line HT29. Protein expression was determined by immunofluorescence. The effect of various proinflammatory stimuli in mRNA and protein expression was studied. TL1A mRNA and protein expression in primary SEMFs (and 18CO cells) was significantly upregulated after stimulation with interleukin 1-alpha and/or tumor necrosis factor alpha (TNF-alpha) (32- to 44-fold increase, P < 0.05 vs unstimulated). Following stimulation with interleukin 1-alpha + TNF alpha + IFN-gamma, HT-29 cells highly expressed DR3 (4.1-fold over unstimulated, P = 0.008) and DcR3 (56-fold, P = 0.009) and secreted soluble factors that led to induction of TL1A mRNA in primary SEMFs (28-fold, P = 0.008). Activated epithelial cells significantly upregulated IL-8 expression in response to stimulation with recombinant TL1A. Supernatants from mucosal cultures of patients with CD were able to stimulate the expression of TL1A in cultured primary SEMFs, in comparison to supernatants from healthy controls (3.8-fold increase, P < 0.05) or culture media alone (P < 0.05). In conclusion, we found that proinflammatory cytokines are important regulators of the expression of TL1A in SEMFs and of its receptors in intestinal epithelial cells. Our results raise the possibility for involvement of TL1A/DR3/DR3-mediated mechanisms in epithelial-mesenchymal interactions and the development of inflammation-induced intestinal fibrosis in CD. PMID- 27665178 TI - Development of 6-arylcoumarins as nonsteroidal progesterone antagonists. Structure-activity relationships and fluorescence properties. AB - Progesterone is involved in multiple physiological processes, including female reproduction, via binding to the progesterone receptor (PR). We have developed 6 arylcoumarins such as 5 and 6 as non-steroidal PR antagonists with receptor binding-dependent fluorescence. In this study, we investigated the structure activity relationships and fluorescence properties of coumarin derivatives bearing a heterocyclic aromatic moiety. Among these derivatives, 7c (IC50: 34nM) and 10b (IC50: 24nM) showed more potent PR-antagonistic activity than lead compounds 5 (IC50: 500nM) and 6 (IC50: 65nM) in alkaline phosphatase (AP) assay. Compound 9b showed solvent-dependent fluorescence intensity, exhibiting strong fluorescence in the presence of PR LBD only in buffer solution. On the other hand, 10b showed a solvent-dependent shift of the fluorescence maximum wavelength in the presence of PR LBD. These results indicate that 6-arylcoumarin will be a useful scaffold for PR antagonists and fluorescent probes targeting PR. PMID- 27665179 TI - Investigation of C-5 alkynyl (alkynyloxy or hydroxymethyl) and/or N-3 propynyl substituted pyrimidine nucleoside analogs as a new class of antimicrobial agents. AB - The resurgence of mycobacterial infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6-10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5 (2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2 propynyl) (30-33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium tuberculosis (Mtb), Mycobacterium bovis (BCG) and Mycobacterium avium], gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and gram-negative bacteria (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) alone and in combination with existing drugs in in vitro assays. Although several compounds exhibited marked inhibitory activity at a higher concentration against Mtb, M. bovis, S. aureus and E. faecalis, they displayed unexpected synergistic and additive interactions at their lower concentrations with antitubercular drugs isoniazid and rifampicin, and antibacterial drug gentamicin. The active analogues were also found to inhibit intracellular Mtb in a human monocytic cell line infected with H37Ra. Oral administration of 5-hydroxymethyl-3-N-(2-propynyl)-3'-azido-2',3' dideoxyuridine (32) and 5-hydroxymethyl-3-N-(2-propynyl)-2',3'-dideoxyuridine (33) at a dose of 100mg/kg for two weeks showed promising in vivo effects in mice infected with Mtb (H37Ra). No in vitro cytotoxicity of the test compounds was observed up to the highest concentration tested (CC50>300MUg/mL). PMID- 27665180 TI - Design and synthesis of novel HDAC8 inhibitory 2,5-disubstituted-1,3,4 oxadiazoles containing glycine and alanine hybrids with anti cancer activity. AB - Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. Of the four oxadiazoles known, 1,3,4-oxadiazole has become an important structural motif for the development of new drugs and the compounds containing 1,3,4-oxadiazole cores have a broad spectrum of biological activity. Herein, we describe the design, synthesis and biological evaluation of a series of novel 2,5-disubstituted 1,3,4-oxadiazoles (10a-10j) as class I histone deacetylase (HDAC) inhibitors. The compounds were designed and evaluated for HDAC8 selectivity using in silico docking software (Glide) and the top 10 compounds with high dock score and obeying Lipinski's rule were synthesized organically. Further the biological HDAC inhibitory and selectivity assays and anti-proliferative assays were carried out. In in silico and in vitro studies, all compounds (10a-10j) showed significant HDAC inhibition and exhibited HDAC8 selectivity. Among all tested compounds, 10b showed substantial HDAC8 inhibitory activity and better anticancer activity which is comparable to the positive control, a FDA approved drug, vorinostat (SAHA). Structural activity relation is discussed with various substitutions in the benzene ring connected on 1,3,4 oxadizole and glycine/alanine. The study warranted further investigations to develop HDAC8-selective inhibitory molecule as a drug for neoplastic diseases. Novel 1,3,4-oxadizole substituted with glycine/alanine showed HDAC8 inhibition. PMID- 27665181 TI - Delayed HBV reactivation in rituximab-containing chemotherapy: How long should we continue anti-virus prophylaxis or monitoring HBV-DNA? AB - Reactivation of hepatitis B virus (HBV) infection is a well-recognized and potentially fatal complication in patients treated with chemotherapy for lymphoid malignancies. Although several guidelines recommend antiviral prophylaxis and/or monitoring for HBV-DNA, there is no consensus over what time period these should occur. Clinically, we have encountered delayed reactivation of HBV infections and have reported 12 cases of reactivation in patients. Among them, five patients developed HBV reactivation more than a year after they completed their chemotherapy. This means there can be a delayed HBV reactivation and prolonged monitoring of more than a year after cessation of chemotherapy may be needed. Hence, the current recommendation of stopping antiviral prophylaxis 6-12 months after the cessation of chemotherapy may not fully protect all patients from HBV reactivation. The optimal duration of follow-up needs to be determined, and until better guidelines are set, there is no choice but to keep monitoring patients for reactivation for as long as practicable. PMID- 27665182 TI - Synthesis, spectroscopic, physicochemical properties and binding site analysis of 4-(1H-phenanthro[9,10-d]-imidazol-2-yl)-benzaldehyde fluorescent probe for imaging in cell biology: Experimental and theoretical study. AB - In this study, the 4-(1H-phenanthro[9,10-d]-imidazol-2-yl)-benzaldehyde (PB1) was investigated as a fluorescent dye. For this reason, the spectroscopic properties in different solvents were thoroughly studied. The experimental data were supported by quantum-chemical calculations using density functional theory. Measurements and theoretical calculations showed that PB1 dye is characterized by the non-monotonic solvatochromism, strongly polar charge transfer excited state, large Stokes' shift, high fluorescence quantum yield and high fluorescence lifetime. Simulations using AutoDock presented in this study, showed that after conjugation with Concanavalin A in the active site with LYS116, the PB1 possesses the highest probability of binding affinity. The interaction between the PB1 dye and the Concanavalin A lectin has been investigated by circular dichroism spectroscopy. Conventional fluorescence microscopy imaging of Candida albicans and Yarrowia lipolytica cells, incubated with the PB1-Concanavalin A, was demonstrated. Results show that the PB1 dye is a photostable low molecular weight fluorescent probe, which emits a blue fluorescence. The results of this study have implications for designing PB1-protein conjugate as a valuable alternative to commercial probes designed for cellular labeling in biological and biomedical research. Calculated LogP value together with LogBCF show that PB1-protein conjugate is a valuable alternative to commercial probes designed for cellular labeling in biological and biomedical research. PMID- 27665183 TI - FRET energy transfer via Pdots improves the efficiency of photodynamic therapy and leads to rapid cell death. AB - Photodynamic therapy (PDT) is well established as a clinical treatment modality for various diseases, including cancer and especially for the treatment of superficial tumors. However, one of the disadvantages of the photoactivatable molecules is their low absorbance in the optical window for photosensitizer excitation. The use of nanoparticles in photodynamic therapy can address this deficiency and improve treatment efficiency. Pdots are nano-sized particles, composed of conjugated chromophoric polymers. By mixing them with PEGylated phospholipids they can become soluble and stable colloids. They exhibit a broad absorption band with a strong and narrow emission band. In this study, we examined two types of Pdots (MEH-PPV and CN-PPV) with two different lengths of the PEGylated lipids coating, 350 and 2000. When a photosensitizer, such as mTHPC, comes in close contact with the amphiphilic coating of the Pdots, a very efficient fluorescence resonance energy transfer (FRET) occurs between the donor, the Pdots and the acceptor, the sensitizer. This process, together with the significant uptake of the Pdots-sensitizer pair by MCF-7 cancerous cells causes irreversible damage to the cells. This damage is greater when the Pdots are comprised from the CN-PPV polymer and coated with the PEG2000-PE lipid. Altogether, we demonstrate that implementing FRET energy transfer in the PDT protocol leads to quicker and more aggressive cell death, thus improving the efficacy of the photodynamic therapy. PMID- 27665184 TI - An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease. AB - BACKGROUND: We present an unusual neuroimaging finding in a young girl with genetically confirmed vanishing white matter disease and a possible response to immunotherapy. METHODS AND RESULTS: 2.5 yr old girl, presented with acute onset unsteadiness and encephalopathy following a viral illness. MRI showed global symmetric white matter abnormality, with symmetric enhancement of cranial nerves (III and V) and of cervical and lumbar roots. She received immunotherapy for her encephalopathic illness with white matter changes. Follow up neuroimaging showed resolution of white matter edema and resolution of the change in the brainstem. Genetic testing confirmed a diagnosis of vanishing white matter disease (VWMD). CONCLUSION: Craniospinal nerve enhancement and possible response to immunotherapy has not been described in vanishing white matter disease. PMID- 27665185 TI - Nursing homes and long-term care facilities: Reservoirs of CTX-M-15-producing Escherichia coli O25b-ST131 in Portugal. PMID- 27665187 TI - Silk suture granuloma with false-positive findings on PET/CT accompanied by peritoneal metastasis after colon cancer surgery. AB - INTRODUCTION: Suture granuloma is a rare benign tumor caused by suture material, which usually appears several months or years after surgery. PRESENTATION OF CASE: A 71-year-old man underwent sigmoidectomy and partial hepatectomy (S6) for sigmoid colon cancer and synchronous liver metastasis at a previous hospital. At 4 postoperative months, surveillance computed tomography (CT) revealed a suspicious tumor at the hepatic resection stump. He was referred to our hospital for further examinations and treatments. Positron emission tomography/CT (PET/CT) revealed abnormal hepatic F-18 fluorodeoxyglucose (FDG) uptake below the diaphragm at the S5/S8 surface. Peritoneal metastasis was suspected and surgery was performed. White nodules were found in the Douglas pouch. A diagnosis of adenocarcinoma was confirmed by frozen section analysis of the nodules. He underwent a partial hepatectomy (S5/S8) and partial resection of the diaphragm. Pathological examination showed that the liver tumor was a foreign body granuloma that included silk suture material. DISCUSSION: Although postoperative PET/CT surveillance is useful following malignant tumor resection, it is important to note that PET/CT false-positive findings are possible. Furthermore, PET/CT cannot detect small peritoneal metastases, necessitating a thorough abdominal examination. CONCLUSION: In cases of malignancy, the possibility of postoperative suture granuloma should be considered. In addition, a thorough surgical examination of the abdomen should be performed in cases of suspected recurrence. PMID- 27665186 TI - Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia. AB - Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund's adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05). After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA) in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene related peptide (CGRP) in the dorsal root ganglia (DRG) tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS) production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC) and small-interfering RNA (siRNA) silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia. PMID- 27665188 TI - Characterization of chlorophyll derivatives in micelles of polymeric surfactants aiming photodynamic applications. AB - The spectrophotometric properties of chlorophylls' derivatives (Chls) formulated in the Pluronics(r) F-127 and P-123 were evaluated and the results have shown that the Chls were efficiently solubilized in these drug delivery systems as monomers. The relative location of the Chls in the Pluronics(r) was estimated from the Stokes shift and micropolarity of the micellar environment. Chls with phytyl chain were located in the micellar core, where the micropolarity is similar to ethanol, while phorbides' derivatives (without phytyl chain) were located in the outer shell of the micelle, i.e., more polar environment. In addition, the thermal stability of the micellar formulations was evaluated through electronic absorption, fluorescence emission and resonance light scattering with lowering the temperature. The Chls promote the stability of the micelles at temperatures below the Critical Micellar Temperature (CMT) of these surfactants. For F-127 formulations, the water molecules drive through inside the nano-structure at temperatures below the CMT, which increased the polarity of this microenvironment and directly affected the spectrophotometric properties of the Chls with phytyl chain. The properties of the micellar microenvironment of P 123, with more hydrophobic core due to the small PEO/PPO fraction, were less affected by lowering the temperature than for F-127. These results enable us to better understand the Chls behavior in micellar copolymers and allowed us to design new drug delivery system that maintains the photosensitizer's properties for photodynamic applications. PMID- 27665190 TI - Influence of structural and solvation factors on the spectral-fluorescent properties of alkyl-substituted BODIPYs in solutions. AB - The spectral-fluorescent properties of alkyl-substituted BODIPYs 1-5 in organic solvents were investigated. The alkyl-substituted BODIPYs 1-5 exhibit intense chromophoric properties (lgepsilon=4.60-5.00). Relative fluorescence quantum yield of studied compounds reaches 66-100% and weakly dependent on the structural and solvation effects. Introduction of methyl, propyl, amyl and heptyl substituents in the 2,6-positions of the pyrroles the results in a significant red shift (22-29nm) in the electronic absorption and fluorescence spectra. PMID- 27665189 TI - "On-off" fluorescent sensors for aromatic analytes based on zinc(II) bis(dipyrromethenate)s. AB - This paper presents the results of spectral-luminescence research of binuclear zinc(II) helicates with tetra-, octa-, and decamethylsubstituted 3,3' bis(dipyrromethene)s ([Zn2L2]) in binary mixtures of cyclohexane with aromatic hydrocarbons (benzene, toluene, and m-xylene). Structure effects of zinc(II) helicates, and aromaticity criteria of analytes (HOMA, NICS, delta) on the fluorescence quenching efficiency of [Zn2L2] in the presence of aromatic compounds was considered. It was found that decamethylsubstituted 3,3' bis(dipyrromethenate)s compared to tetra-, and octamethylsubstituted-analogs shows the highest fluorescence sensitivity to the presence of aromatic compounds. High specificity of spectral-luminescence characteristics changing in the presence of particular aromatic analytes provides the possibility of using [Zn2L2] helicates as new fluorescent sensors of aromatic compounds trace amount (120ppb to 56ppm) in organic media. PMID- 27665191 TI - Pyrene excimer-based fluorescent sensor for detection and removal of Fe3+ and Pb2+ from aqueous solutions. AB - Pyrene excimer usually serves as a chromogenic unit for developing ratiometric fluorescent sensors. But this study used excimer as a large hydrophobic group to regulate the molecular hydrophobicity, and obtained a new fluorescent sensor, N, N-bi[4(1-pyrene)-butyroyl]ornithine (1), for detection and removal of Fe3+ and Pb2+ from aqueous solutions. The coordination of 1 and Fe3+ in the aqueous solution or even pure water forms removable flocculent precipitates, accompanied by obvious fluorescent quenching of emission spectra. In aqueous solutions containing 40% (v/v) acetonitrile, the special responses exhibit a high selectivity and sensitivity to Fe3+ over other common metal ions. However, in aqueous solutions containing 40% (v/v) dimethylsulfoxide, the probe exhibits the analogous fluorescent quenching responses and the removable flocculent precipitates in the presence Fe3+ and Pb2+. These results indicate that the extremely hydrophobic 1-Fe3+/Pb2+ complexes are not only a supplement to the fluorescent sensing of Fe3+ and Pb2+, but also a requirement to the removal of Fe3+ and Pb2+ from aqueous solutions. PMID- 27665192 TI - 2,3-Pyridine dicarboxylic acid functionalized gold nanoparticles: Insight into experimental conditions for Cr3+ sensing. AB - Selectivity of gold nanoparticles (AuNPs) depends upon surface functionality; small changes in structure or concentration bring significant changes in the behavior of AuNPs. In this study, citrate-capped AuNPs were functionalized with ortho-dicarboxylate substituted pyridine (2,3-PDCA) and detailed studies on experimental conditions were carried out to check the stability of AuNPs and response for Cr3+. Stability of PDCA-AuNPs was found sensitive to the pH, ionic strength of buffer and its type. Capping behavior of PDCA on C-AuNPs was examined by FTIR spectroscopy. Surface morphology and size of synthesized AuNPs were confirmed by AFM, XRD, and DLS techniques where particles were found 11nm in size, monodisperse and spherical in shape. Interaction of stabilized AuNPs was tested with various metal ions; where Cr3+ induced the changes in localized surface plasmon band (LSPR) of PDCA-AuNPs which leads to a color change from wine red to violet blue. The phenomenon is explained as cooperative effect of citrate and pyridine nitrogen on surface of AuNPs in contrary to meta-dicarboxylate substituted pyridine derivatives. Further, under optimized and controlled conditions Cr3+ shows linear response with decrease in absorbance at LSPR intensity of AuNPs (518nm). Moreover, to demonstrate the applicability of method, Cr3+ was determined in the presence of Cr (VI) which shows 96% recovery. PMID- 27665193 TI - Interaction of bombesin and its fragments with gold nanoparticles analyzed using surface-enhanced Raman spectroscopy. AB - This work demonstrates the application of commercially available stable surface composed of gold nanograins with diameters ranging from 70 to 226nm deposited onto silicon wafer for surface-enhanced Raman scattering investigations of biologically active compounds, such as bombesin (BN) and its fragments. BN is an important neurotransmitter involved in a complex signaling pathways and biological responses; for instance, hypertensive action, contractive on uterus, colon or ileum, locomotor activity, stimulation of gastric and insulin secretion as well as growth promotion of various tumor cell lines, including: lung, prostate, stomach, colon, and breast. It has also been shown that 8-14 BN C terminal fragment partially retains the biological activity of BN. The SERS results for BN and its fragment demonstrated that (1) three amino acids from these peptides sequence; i.e., l-histidine, l-methionine, and l-tryptophan, are involved in the interaction with gold coated silicon wafer and (2) the strength of these interactions depends upon the aforementioned amino acids position in the peptide sequence. PMID- 27665194 TI - Substituent effect in the photochromism of two isomeric asymmetric diarylethenes having pyrrole and thiophene units. AB - Two new asymmetric isomeric diarylethenes having pyrrole and thiophene units have been synthesized by one-pot reaction and characterized by single crystal X-ray diffraction analysis. The two prepared diarylethenes had disparate crystal structures, and they exhibited distinctly different photochromic behavior, both in solution and in the solid state. Their photochromism, fatigue resistance, and fluorescence were investigated systematically. The methyl group at the reactive carbon atom could significantly enhance the quantum yield of cyclization step and decrease the quantum yield of cycloreversion step, whereas a cyano group at the same position could notably suppress the photocyclization reaction and promote the photocycloreversion reaction. The results indicated that the substituent at the reactive carbon atom could readily modulate the optoelectronic and physical properties for these diarylethenes. PMID- 27665195 TI - Sexual Function After Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Cancer: Results From the Randomized Phase III HYPRO Trial. AB - INTRODUCTION: Hypofractionated radiotherapy could increase the radiobiological tumor dose for localized prostate cancer. The effects of hypofractionation on sexual function are not well known. AIM: To compare sexual function in patients with prostate cancer treated with 78 Gy in 39 fractions of 2 Gy or 64.6 Gy in 19 fractions of 3.4 Gy. METHODS: In total, 820 men with intermediate- to high-risk T1b-T4NX-0MX-0 prostate cancer were enrolled in the phase III HYPRO trial (2007 2010) and randomized to conventional fractionation (39 * 2 Gy) or hypofractionation (19 * 3.4 Gy). Sexual function was assessed at baseline and at 6, 12, 24, and 36 months after treatment using the International Index of Erectile Function (IIEF). For this analysis, patients (n = 322) with a baseline assessment, at least one follow-up assessment, and no or short-term (6-month) androgen-deprivation therapy were included. MAIN OUTCOME MEASURES: Mean IIEF domain scores were compared between treatments in the total population and the hormone-naive population (n = 197) using the independent t-test. Incidences of severe erectile dysfunction (domain score < 11) at last follow-up were calculated in patients with partial or full baseline function. Binary logistic regression analyses were applied to calculate the odds ratio of hypofractionation vs conventional fractionation and to adjust for clinical factors. RESULTS: Median age was 71 years (interquartile range = 67-71) and median follow-up was 37 months (interquartile range = 25-38). Androgen-deprivation therapy was prescribed in 125 (39%). IIEF domain scores decreased after treatment but were comparable between treatment arms at baseline and during follow-up. Orgasmic function scores in hormone-naive patients were significantly higher at 3 years after hypofractionation (4.08 vs 2.65, P = .031). In patients (n = 120) with partial or full baseline erectile function, the incidence of erectile dysfunction at last follow-up was 34.4% for hypofractionated treatment vs 39.3% for conventional treatment (adjusted odds ratio = 0.84, 95% CI = 0.37-1.90, P = .67). CONCLUSION: No significant differences in erectile functioning between conventional and hypofractionated radiotherapy were found. Hormone-naive patients reported significantly higher orgasmic function scores at 3 years after hypofractionation. PMID- 27665196 TI - Determinants of Women's Sexual Dissatisfaction: Assessing a Cognitive-Emotional Model. AB - INTRODUCTION: Recent studies have demonstrated the role of sexual dysfunctional beliefs, negative automatic thoughts, and emotional responses in relation to sexual functioning. Nevertheless, no studies seem to have evaluated the role of these cognitive-emotional factors in determining sexual dissatisfaction. AIM: To test a cognitive-emotional model of sexual dissatisfaction in women. METHODS: In total, 207 women answered questionnaires assessing sexual dissatisfaction and cognitive and emotional variables that might affect sexual dissatisfaction. MAIN OUTCOME MEASURES: Sexual dissatisfaction was measured by the Index of Sexual Satisfaction, sexual beliefs were measured by the Sexual Dysfunctional Beliefs Questionnaire, and thoughts and emotional responses were measured by the Sexual Modes Questionnaire. RESULTS: A path analysis was conducted to assess the conceptual model proposed. Results indicated that dysfunctional sexual beliefs work as predisposing factors by eliciting negative automatic thoughts and emotions, which impair the processing of erotic stimuli and interfere negatively with sexual satisfaction. CONCLUSION: This finding suggests a role for cognitive and emotional factors in predisposing and maintaining sexual dissatisfaction in women, suggesting relevant implications for intervention. PMID- 27665197 TI - Involvement of NADPH oxidase and NF-kappaB activation in CXCL1 induction by vascular endothelial growth factor in human endometrial epithelial cells of patients with adenomyosis. AB - Chemokines were known to participate in inflammation and angiogenesis but have been recently recognized to be involved in embryonic implantation and endometrium related pathologies. Among these chemokines, the CXC chemokines, such as CXCL1, have potential roles to work as biomarkers to identify patients with uterine adenomyosis. In this study, human endometrial epithelial cells (HEECs) were derived from patients' endometrium with adenomyosis. The inductive effects of CXCL1 production by various mediators/growth factors were investigated in the HEECs. Of the tested mediators, VEGF was found to be the most effective. The immunohistochemistry and RT-PCR analysis revealed a positive staining for VEGF and CXCL1 at the epithelium and the presence of CXCL1 in the human endometrium specimens, respectively. The CXCL1 induction by VEGF could be reduced by the antagonist for VEGF receptor (VEGFR), and by the inhibitors for NADPH oxidase and NF-kappaB signaling pathway. However, it was not affected by sex hormones and the inhibitors for MAPKs, PI-3K, protein kinase A and C. In parallel, VEGF induced p47 phox NADPH oxidase activation, IkappaBalpha phosphorylation, NF-kappaB translocation and NF-kappaB-DNA complex formation in the HEECs. Moreover, the CXCL1 released by the HEECs with VEGF stimulation attracted vascular endothelial cell migration. Taken together, we show that VEGF and CXCL1 are expressed in epithelium of the endometrium with adenomyosis and demonstrate here for the first time that VEGF is capable of inducing CXCL1 expression in HEECs through VEGFR, p47 phox NADPH oxidase and NF-kappaB signaling pathway, which is functionally required for attracting vascular endothelial cell migration. PMID- 27665198 TI - Crowding out or no crowding out? A Self-Determination Theory approach to health worker motivation in performance-based financing. AB - Performance-based financing (PBF) is a common health system reform approach in low and middle income countries at present. Although increasing evidence on the effectiveness of PBF and knowledge of principles of good design are available, research is still lacking in regards to other aspects. Among these are a yet limited understanding of the complex role of health worker motivation in PBF and of potential side effects, for instance on intrinsic motivation. Our article aims to support meaningful future research by advancing the theoretical discussion around health worker motivation and PBF. We argue that an in-depth understanding of the motivational mechanisms and consequences of PBF at health worker level are of high practical relevance and should be at the heart of the PBF research agenda, and that predominant unidimensional conceptualizations of health worker motivation and descriptive rather than explanatory research approaches are insufficient to fully understand whether, how, and why PBF schemes alter health workers' motivational structures, mindsets, affect, and behavior. We introduce and apply Self-Determination Theory to the context of PBF as a valuable theoretical framework for future empirical exploration. From this, we conclude that PBF interventions are unlikely to have a generally adverse effect on intrinsic motivation as feared by parts of the PBF community. Rather, we posit that PBF can have positive and negative effects on both intrinsic and extrinsic motivation, to varying degrees depending on the specific design, implementation, and results of a particular intervention and on health workers' perceptions and evaluations of it. PMID- 27665199 TI - Social mobility and subclinical atherosclerosis in a middle-income country: Association of intra- and inter-generational social mobility with carotid intima media thickness in the Brazilian Longitudinal Study of Adult Health (ELSA Brasil). AB - Over the past half century Brazil has undergone a process of dramatic industrialization and urbanization. Cardiovascular diseases (CVD) have become common due to rapid demographic, epidemiologic, and nutritional transitions. The association of social mobility with subclinical CVD has been rarely explored, particularly in developing societies. We investigated the association of intra- and inter-generational social mobility with carotid intima-media thickness (IMT), a marker of subclinical or asymptomatic atherosclerosis, in a large Brazilian sample (ELSA-Brasil). We used baseline data (2008-2010) for 7343 participants from ELSA-Brasil. Intra-generational social mobility was defined as the change in occupational social class between participants' first occupation and current occupation. Inter-generational social mobility was defined as the change in occupational social class of the head of the household when the participant started working and participants' current occupation. Social mobility groups were classified as: stable high (reference), upward, downward and stable low. Linear regression models were used to examine the associations between type of social mobility and IMT. Compared to those who experienced stable high occupational status across generations, downward inter-generational mobility was associated with greater IMT. Additionally, those who declined the most in occupational status had the highest values of IMT, even after adjustments for lifestyle and cardiovascular factors. For intra-generational mobility, stable low versus stable high social mobility was independently associated with higher IMT. Subclinical atherosclerosis is patterned by socioeconomic status both within and across generations, demonstrating an association even before symptoms of CVD appear. The health consequences of downward inter-generational social mobility were not fully explained by lifestyle and cardiovascular factors, whereas being consistently exposed to low occupational status within one's own adulthood was associated with greater IMT, suggesting a cumulative risk model. Primary prevention of atherosclerosis should be complemented by macrosocial policies aimed to reduce downward socioeconomic mobility between generations. PMID- 27665200 TI - Fund my treatment!: A call for ethics-focused social science research into the use of crowdfunding for medical care. AB - Crowdfunding involves raising money from large groups of individuals, often through the use of websites dedicated to this purpose. Crowdfunding campaigns aimed at raising money to pay for expenses related to receiving medical treatment are receiving increased media attention and there is evidence that medical crowdfunding websites are heavily used. Nonetheless, virtually no scholarly attention has been paid to these medical crowdfunding campaigns and there is no systematic evidence about how widely they are used and for what reasons, and what effects they have on the provision of medical care and individuals' relationships to their health systems. Ethical concerns have been raised in relation to these campaigns, focusing on issues for campaigners and donors such as exposure to fraudulent campaigns, loss of privacy, and fairness in how medical crowdfunding funds are distributed. Medical crowdfunding websites themselves have not been systematically studied, despite their significant influence on how these campaigns are developed and promoted. In this paper, we identify three very broad and pressing ethical questions regarding medical crowdfunding for social scientists to address and offer some preliminary insights into key issues informing future answers to each: Who benefits the most from medical crowdfunding and how does medical crowdfunding affect access to medical care; How does medical crowdfunding affect our understanding of the causes of inadequate access to medical care; and How are campaigner and donor privacy affected by website design? Our observations indicate the need for increased scholarly attention to the ethical and practical effects of medical crowdfunding for campaigners, recipients, donors, and the health system as a whole. PMID- 27665202 TI - Fractionated Gamma Knife surgery for giant pituitary adenomas. AB - OBJECTIVE: To analyze the feasibility and effectiveness of fractionated Gamma Knife surgery (FGKS) for giant pituitary adenomas. METHODS: From June 2005 to May 2016, 14 patients with giant pituitary adenomas were treated with FGKS, and 10 patients (71%) completed follow-up evaluation. All patients had undergone surgical resection at least once prior to FGKS. The median-volume of the adenomas was 17.6cm3(range 4.9-61cm3). RESULTS: The median follow-up period was 31.5 months (range 6-58 months). The size of the tumors decreased in 6 patients and remained stable in 4 patients. The visual acuity improved in 1 patient. None of the patients suffered from vision deterioration caused by FGKS. CONCLUSION: FGKS is an effective treatment modality for giant pituitary adenomas in selected patients. PMID- 27665204 TI - Reply. PMID- 27665203 TI - Depressive Symptoms, Cardiac Disease Severity, and Functional Status in Patients With Coronary Artery Disease (from the Heart and Soul Study). AB - Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly influenced by depressive symptoms as it is by cardiovascular disease severity. PMID- 27665201 TI - Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study. AB - BACKGROUND AND AIMS: Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort. METHODS: 8127 participants from the ARIC study (4th visit, 1996-1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis. RESULTS: While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis. CONCLUSIONS: These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD. PMID- 27665205 TI - Comparison of Outcomes of Transcatheter Aortic Valve Replacement Plus Percutaneous Coronary Intervention Versus Transcatheter Aortic Valve Replacement Alone in the United States. AB - Transcatheter aortic valve replacement (TAVR) with percutaneous coronary intervention (PCI) has emerged as a less-invasive therapeutic option for high surgical risk patients with aortic stenosis and coronary artery disease. The aim of this study was to determine the outcomes of TAVR when performed with PCI during the same hospitalization. We identified patients using the International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes from the Nationwide Inpatient Sample between the years 2011 and 2013. A total of 22,344 TAVRs were performed between 2011 and 2013. Of these, 21,736 (97.3%) were performed without PCI (TAVR group) while 608 (2.7%) along with PCI (TAVR + PCI group). Among the TAVR + PCI group, 69.7% of the patients had single-vessel, 22.2% had 2-vessel, and 1.6% had 3-vessel PCI. Drug-eluting stents were more commonly used than bare-metal stents (72% vs 28%). TAVR + PCI group witnessed significantly higher rates of mortality (10.7% vs 4.6%) and complications: vascular injury requiring surgery (8.2% vs 4.2%), cardiac (25.4% vs 18.6%), respiratory (24.6% vs 16.1%), and infectious (10.7% vs 3.3%), p <0.001% for all, compared with the TAVR group. The mean length of hospital stay and cost of hospitalization were also significantly higher in the TAVR + PCI group. The propensity score-matched analysis yielded similar results. In conclusion, performing PCI along with TAVR during the same hospital admission is associated with higher mortality, complications, and cost compared with TAVR alone. Patients would perhaps be better served by staged PCI before TAVR. PMID- 27665206 TI - Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT). AB - Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score >=1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Delta = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Delta = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR. PMID- 27665207 TI - Factors Associated With Resource Utilization and Coronary Artery Dilation in Refractory Kawasaki Disease (from the Pediatric Health Information System Database). AB - Management guidelines for refractory Kawasaki disease (KD) are vague. We sought to assess practice variation and identify factors associated with large/complex coronary artery aneurysms (LCAA) and resource utilization in refractory KD. This retrospective cohort study identified patients aged <=18 years with KD (2004 to 2014) using the Pediatric Health Information System. Refractory KD was defined as receiving >1 dose of intravenous immunoglobulin. Demographics, medications, concomitant infections, length of stay (LOS), and charges were collected. Antithrombotic therapy was a surrogate for LCAA. LOS and hospital charges assessed resource utilization. Multivariate regression identified factors associated with LOS, charges, and LCAA. Of 14,194 patients with KD, 2,974 (21%) had refractory KD and 203 of those 2,974 (7%) had LCAA. Additional intravenous immunoglobulin was the sole medication in 77%. Other medications added were steroids (18%), infliximab (2%), and both (3%). Warfarin, low-molecular-weight heparin, tissue plasminogen activator, and clopidogrel were prescribed with equal frequency (2%). Male gender (adjusted relative risk 1.52, 95% confidence interval [CI] 1.08 to 2.16, p <0.01), admission to an intensive care unit (4.79, 95% CI 3.40 to 6.74, p <0.001), arrhythmia (3.00, 95% CI 1.94 to 4.65, p <0.001), and concomitant viral infection (2.29, 95% CI 1.49 to 3.52, p <0.001) were associated with LCAA. Severe illness, race, region, and payer were independently associated with increased charges (p <0.05 for all). In conclusion, treatment for refractory KD varies widely. Concomitant viral infection was associated with a greater risk of LCAA in refractory KD. Better understanding of optimal management may improve outcomes and decrease both variability in management and resource utilization for refractory KD. PMID- 27665208 TI - Clinical Evaluation Versus Undetectable High-Sensitivity Troponin for Assessment of Patients With Acute Chest Pain. AB - Decision-making in acute chest pain remains challenging despite normal (below ninety-ninth percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ninety-ninth percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised 682 patients (November 2010 to September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/l). The main end point was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina, or revascularization) at a 4-year median follow-up; secondary end point was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain) and 2 points (recurrent pain and prior ischemic heart disease). The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/l), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI(Thrombolysis In Myocardial Infarction) risk (0.68, 0.77) or GRACE(Global Registry of Acute Coronary Events) (0.50, 0.47) scores. Likewise, the negative predictive values of score = 0 (97.5%, 100%) and <=1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both clinical scores of 0 and <=1 better classified patients at risk of MACE (p = 0.0001, log rank test) than hs-cTnT <5 ng/l (p = 0.06). In conclusion, clinical data can guide decision-making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs cTnT. PMID- 27665209 TI - Harm reduction workers and the challenge of engaging couples who inject drugs in hepatitis C prevention. AB - AIMS: Despite injecting-equipment sharing between sexual partners leaving them at increased risk of hepatitis C (HCV), there is scant literature available to guide harm reduction workers in their encounters with couples who inject drugs. This article explored workers' understandings of such couples and their accounts of working with them in relation to HCV prevention. METHOD: Semi-structured interviews were conducted with 22 staff of harm reduction services located in Sydney and Melbourne, Australia. RESULTS: Overall, staff represented couples as either absent from the service or as presenting with needs indiscernible from those of individual clients. Responses to questions about HCV and couples were framed primarily in terms of risk. Staff participants questioned 'genuineness' of clients' intimate relationships, instead characterising them as inauthentic and drug-driven. Working with couples was seen to present a number of organisational and clinical challenges. The benefits of recognising and working with such partnerships received scant acknowledgement. Rather, staff tended to perceive couples as being 'impenetrable' to health promotion messaging. DISCUSSION: The framing and delivery of harm reduction in Australia remains an individualising enterprise with little capacity to recognise the intimate partnerships, including addressing the HCV risks specific to them. More effective harm reduction strategies may be achieved by transitioning to a practice framework that addresses the social context of injecting, including the experience of couples. This would require direct involvement of couples who inject drugs. PMID- 27665210 TI - Vissia and co-workers claim that DID is trauma-based. But how strong is their evidence? PMID- 27665211 TI - Compliance with serial dermoscopic monitoring: An academic perspective. AB - BACKGROUND: For even seasoned practitioners, early melanomas can be difficult to distinguish from melanocytic nevi. Although serial digital dermoscopy is considered by many to be the gold standard for monitoring patients at high risk, poor compliance can seriously alter efficacy. In 2014, a concerning compliance rate of 25% was reported from a single, private clinic. Information is currently limited regarding the determinants of compliance and whether patients at high risk return at an acceptable rate. OBJECTIVE: We sought to determine the compliance rate within the pigmented lesions clinic at our academic institution and identify demographic variables that may influence adherence. METHODS: A retrospective review was conducted using 120 patient charts. RESULTS: An overall compliance rate of 87.5% was observed with 63.3% of patients returning within 1 month of the recommended interval. The most notable risk factor for noncompliance was patient age between 20 and 29 years. Factors promoting adherence include a personal history of melanoma, greater than 5 serially monitored nevi, and a personal history of atypical nevi. LIMITATIONS: The external validity is limited and the sample size is small. CONCLUSION: These findings contradict concerns that adherence to serial monitoring is unacceptably poor and demonstrate that compliance is highest for patients with the greatest inherent risk. PMID- 27665212 TI - Erratum. PMID- 27665213 TI - Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay. AB - PURPOSE: To measure matrix metalloproteinase 9 (MMP-9) in the tear film of patients with dry eye disease (DED) compared with controls and to correlate clinical findings. DESIGN: In a prospective study, 101 patients and controls underwent MMP-9 testing of the tear film. Thereafter, they were evaluated for symptoms and signs of DED. PARTICIPANTS: Included patients were those who showed 3 of the following 4 dry eye criteria: ocular surface disease index (OSDI) score of more than 12, tear film break-up time (TBUT) of 10 seconds or less, Schirmer test results without anesthesia of less than 10 mm/5 minutes, and corneal staining results of 1 or more. Fifty-four healthy eyes and 47 eyes fulfilling diagnostic criteria for DED of various levels of severity were included in this study. METHODS: The tear film was analyzed for MMP-9 by a commercially available test (InflammaDry; Rapid Pathogen Screening, Inc, Sarasota, FL) detecting MMP-9 levels of more than 40 ng/ml. Symptoms and signs of DED were evaluated using the OSDI questionnaire, TBUT, conjunctival and corneal staining, Schirmer test results without anesthesia, and meibomian gland examination. These findings were correlated to results of the MMP-9 test in tears. MAIN OUTCOME MEASURES: Positive MMP-9 results in tears. RESULTS: In 19 of 47 patients confirmed with dry eye (40.4%) and in 3 of 54 controls (5.6%), the MMP-9 results were positive. This difference was statistically significant (P < 0.001). Thus, the MMP-9 results indicated a clinically significant inflammation in 40% of dry eye patients. Positive results correlated well with subjective symptoms of DED evaluated by OSDI (P = 0.001), TBUT of less than 5 seconds (P < 0.013), Schirmer test results (P < 0.001), conjunctival staining (P < 0.001), and corneal staining (P = 0.007). Moreover, MMP-9 results correlated with the number of obstructed meibomian ducts (P = 0.005) and a pathologic meibomian gland secretion (P = 0.001). The MMP-9 results were increased significantly in women (P < 0.001) and in patients with autoimmune disease (P = 0.005), especially Sjogren's syndrome (P = 0.001) and thyroid disease (P = 0.012). CONCLUSIONS: Matrix metalloproteinase 9 testing in DED is a valuable new diagnostic tool. It correlated well with other dry eye tests and identified the presence of ocular surface inflammation in 40% of confirmed dry eye patients. It may be especially helpful to identify patients with ocular surface inflammation and autoimmune disease and may facilitate the decision to institute anti-inflammatory treatment in these patients. PMID- 27665214 TI - Histopathologic Features of Descemet Membrane Endothelial Keratoplasty Graft Remnants, Folds, and Detachments. AB - PURPOSE: To describe the histologic features of postmortem eyes after Descemet membrane endothelial keratoplasty (DMEK) and their potential clinical implications. DESIGN: Histopathologic study. PARTICIPANTS: Eleven postmortem DMEK corneas of 8 patients who underwent surgery for Fuchs endothelial dystrophy, with an average postoperative time of 4+/-1.9 years (range, 7 months-6.5 years). METHODS: Eleven corneas transplanted with a DMEK graft were procured after death and processed for light microscopy evaluation. MAIN OUTCOME MEASURES: Histologic findings at the donor-host interface and at the host edge. RESULTS: Of the 11 corneas available for analysis, 9 showed normal anatomic features in the corneal center; that is, the donor-host interface resembled that of a virgin eye. One eye also had an anatomically normal periphery, but the remaining 10 eyes showed specific abnormalities in the periphery. Nine demonstrated overlapping of the DMEK graft onto the host edge of the descemetorhexis (and in 6 of these, the overlapping tissue showed a contracted inward fold at its peripheral edge with scar tissue); 1 eye showed a dense, acellular scar overlying a portion of the DMEK graft that clinically had shown a detachment followed by spontaneous adherence; 3 eyes showed subtle graft folds with scar tissue anteriorly; in 2 eyes (of the same patient), the anterior banded layer of the host Descemet membrane (DM) was still in situ across the cornea (both of these eyes had required rebubbling); and 2 eyes showed host DM remnants within the corneolimbal tunnel incision that may have interfered with incisional wound healing. CONCLUSION: Incomplete host DM removal may relate to postoperative DMEK graft detachment and wound instability. Graft detachments may reattach with interface scarring. Rebubbling procedures may be performed within 4 to 6 weeks, before portions of the detached graft scar. Subtle DMEK graft folds may explain subjective reports of monocular diplopia. PMID- 27665216 TI - A qualitative study of how caseload midwifery is experienced by couples in Denmark. AB - BACKGROUND: Caseload midwifery is expanding in Denmark. There is a need for elaborating in-depth, how caseload midwifery influences the partner and the woman during childbirth and how this model of care influences the early phases of labour. AIM: To follow, explore and elaborate women's and their partner's experiences of caseload midwifery. METHODS: Phenomenology of practice was the analytical approach. The methodology was inspired by ethnography, and applied methods were field observations followed by interviews. Ten couples participated in the study. Most of the couples were observed from the onset of labour until childbirth. Afterwards, the couples were interviewed. FINDINGS: The transition from home to hospital in early labour was experienced as positive. During birth, the partner felt involved and included by the midwife. The midwives remembered and recognized the couple's stories and wishes for childbirth and therefore they felt regarded as "more than numbers". Irrespective of different kinds of vulnerability or challenges among the participants, the relationship was named a professional friendship, characterised by equality and inclusiveness. One drawback of caseload midwifery was that the woman was at risk of being disappointed if her expectations of having a known midwife at birth were not fulfilled. KEY CONCLUSIONS: From the perspective of women and their partners, attending caseload midwifery meant being recognised and cared for as an individual. The partner felt included and acknowledged and experienced working in a team with the midwife. Caseload midwifery was able to solve problems concerning labour onset or gaining access to the labour ward. PMID- 27665215 TI - Corneal Epithelial Stem Cells Repopulate the Donor Area within 1 Year from Limbus Removal for Limbal Autograft. AB - PURPOSE: To determine whether limbal epithelial stem cells (LESCs) repopulate the site harvested for limbal autograft transplantation (LAT), the expression of LESCs markers was evaluated in bioptic specimens obtained from the donor area 12 months or more after surgery. DESIGN: Interventional case series. PARTICIPANTS: Patients who underwent LAT for unilateral acquired limbal stem cell deficiency after chemical burn. METHODS: Corneal limbal explants were obtained from 2 sites, the harvested area and the untouched control area, in the donor eyes of 6 patients who previously underwent LAT for unilateral acquired limbal stem cell deficiency after chemical burn. Limbal epithelial stem cells were isolated, and cellular, immunohistochemistry, and histologic parameters were assessed to compare differences between LESCs isolated from harvested or control sites. MAIN OUTCOME MEASURES: Presence of LESCs 1 year or more after LAT. RESULTS: Specific markers (p63, Ki67, K12), percentage of LESCs, cell doubling, and number of passages in culture did not differ significantly between harvested and control sites. However, the distinctive structure of the palisades of Vogt was found only in 2 of 6 harvested sites. CONCLUSIONS: Limbal epithelial stem cells repopulate the donor site as early as 1 year after limbus removal for LAT. Autologous transplantation of conjunctiva and limbus are safe procedures and can be performed in cases that cannot be treated by simple grafting of LESCs cultured ex vivo. PMID- 27665217 TI - Therapeutic Pulsed Ultrasound Promotes Revascularization and Functional Recovery of Rat Skeletal Muscle after Contusion Injury. AB - The mechanism by which therapeutic pulsed ultrasound (TPU) promotes the repair of damaged gastrocnemius muscle was investigated. Male Wistar rats were divided into uninjured, sham-treated injured and TPU-treated injured (TPU) groups. Injury was induced by mass-drop technique. TPU was applied to the injured muscle for 5 min, daily, started at day 1 post-injury and continuing for 3, 7 and 14 d. For 3 d post-injury, a significant reduction in muscle force was observed in both the sham-treated injured and TPU groups. TPU treatment significantly increased recovery force of the injured muscle after day 7 post-injury. This effect of TPU is associated with increased centronucleated fibers and cross-sectional area, mRNA expression of the vascular endothelial growth factor and capillary density of the regenerated fibers, but not with mRNA expression of nitric oxide synthase. We conclude that TPU hastens muscle recovery, at least in part, by upregulating angiogenesis. PMID- 27665218 TI - What was old .... is new again! PMID- 27665219 TI - Wrinkles, folds and calcifications: Reduced durability after transcatheter aortic valve-in-valve replacement. PMID- 27665220 TI - Surgical reconstruction of semilunar valves in the growing child: Should we mimic the venous valve? A simulation study. AB - OBJECTIVES: Neither heart valve repair methods nor current prostheses can accommodate patient growth. Normal aortic and pulmonary valves have 3 leaflets, and the goal of valve repair and replacement is typically to restore normal 3 leaflet morphology. However, mammalian venous valves have bileaflet morphology and open and close effectively over a wide range of vessel sizes. We propose that they might serve as a model for pediatric heart valve reconstruction and replacement valve design. We explore this concept using computer simulation. METHODS: We use a finite element method to simulate the ability of a reconstructed cardiac semilunar valve to close competently in a growing vessel, comparing a 3-leaflet design with a 2-leaflet design that mimics a venous valve. Three venous valve designs were simulated to begin to explore the parameter space. RESULTS: Simulations show that for an initial vessel diameter of 12 mm, the venous valve design remains competent as the vessel grows to 20 mm (67%), whereas the normal semilunar design remains competent only to 13 mm (8%). Simulations also suggested that systolic function, estimated as effective orifice area, was not detrimentally affected by the venous valve design, with all 3 venous valve designs exhibiting greater effective orifice area than the semilunar valve design at a given level of vessel growth. CONCLUSIONS: Morphologic features of the venous valve design make it well suited for competent closure over a wide range of vessel sizes, suggesting its use as a model for semilunar valve reconstruction in the growing child. PMID- 27665221 TI - A derived and validated score to predict prolonged mechanical ventilation in patients undergoing cardiac surgery. AB - OBJECTIVES: Prolonged mechanical ventilation after cardiac surgery imposes a significant burden on the patient in terms of morbidity as well as a financial burden on the hospital. We undertook a retrospective analysis of 2 prospectively collected databases developed in tertiary cardiac care centers to derive and validate a risk index predicting prolonged mechanical ventilation after cardiac surgery. METHODS: We studied a retrospective cohort of 32,045 patients undergoing cardiac surgery in 2 hospitals in Toronto, Canada. The development cohort consisted of 21,661 patients at Toronto General Hospital. Data Sunnybrook Health Sciences Centre, Toronto, Canada, with 10,384 patients, served as an institutional validation cohort. We operationally characterized prolonged mechanical ventilation as the duration from surgery completion to extubation exceeding 48 hours. RESULTS: Prolonged postoperative mechanical ventilation rates in the development and validation cohort were 6% and 7%, respectively. Multivariable regression in the development cohort showed that the following factors were strong predictors of prolonged mechanical ventilation after cardiac surgery: previous cardiac surgery, lower left ventricular ejection fraction, shock, surgery involving repair of congenital heart disease, and cardiopulmonary bypass time. The intraoperative multivariable model retained good discrimination in the validation cohort, achieving a c statistic of 0.787. CONCLUSIONS: Prolonged mechanical ventilation after cardiac surgery can be accurately predicted by readily available pre- and intraoperative information. PMID- 27665222 TI - Ultrasound visualization of the left circumflex artery by direct endocardial scanning of the mitral annulus during surgery. PMID- 27665223 TI - Cardiomyocyte psychology. PMID- 27665224 TI - Good for now, but will they stand the test of time? PMID- 27665225 TI - The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133+ stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy. AB - OBJECTIVES: The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133+ stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. METHODS: After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133+, CD34+, CD45+ triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. RESULTS: There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). CONCLUSIONS: The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133+ cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function. PMID- 27665226 TI - Three-dimensional correlation between trochanteric fossa and the ideal entry point for antegrade femoral nailing. AB - PURPOSE: To verify the practical correlation between the topographical features of the femur neck base and the ideal entry point by analyzing three-dimensional (3D) models virtually implanted with an antegrade femoral nail. MATERIALS AND METHODS: A total of 103 cadaveric femurs (50 males and 53 females) were enrolled. Specimens underwent continuous 1.0mm slice computed tomography (CT) scans. CT images were rendered into 3D images using image-processing software (Mimics(r)) to reconstruct the geometry of the cortex and medullary canal. A real cannulated femoral nail (CFN)(r) was processed into a 3D image using a 3D sensor at the actual size and optimally placed in the femur model using Mimics(r) for virtual implantation. The correlation between the ideal entry point in the cranial view of the proximal femur and the trochanteric fossa was assessed and overlap of trochanter overhang was verified. RESULTS: The entry point of 68 models (66.0%) was the trochanteric fossa, while the others were placed around the anterior border of the trochanteric fossa. The proximal end of the nail overlapped in 50 models (48.1%), and among them, the central point of 23 models (22.3%) was obscured by trochanteric overhang. There was a statistically significant risk associated with female gender (6.02 times) and type IV overhang of Grenchenig's classification (4.56 times). Despite the precise positioning of the trochanteric fossa, 11 models (10.7%) had the entry point covered by trochanteric overhang. CONCLUSION: The ideal entry point was over the trochanteric fossa in just half of the models, and could be hindered by trochanteric overhang even though the CFN was ideally positioned. PMID- 27665227 TI - No small task: therapeutic targeting of Lp(a) for cardiovascular disease. PMID- 27665229 TI - Making the SDGs useful: a Herculean task. PMID- 27665230 TI - Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. AB - BACKGROUND: Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. METHODS: We did two randomised, double-blind, placebo-controlled trials. In a phase 2 trial (done in 13 study centres in Canada, the Netherlands, Germany, Denmark, and the UK), we assessed the effect of IONIS-APO(a)Rx, an oligonucleotide targeting apolipoprotein(a). Participants with elevated Lp(a) concentrations (125-437 nmol/L in cohort A; >=438 nmol/L in cohort B) were randomly assigned (in a 1:1 ratio in cohort A and in a 4:1 ratio in cohort B) with an interactive response system to escalating-dose subcutaneous IONIS APO(a)Rx (100 mg, 200 mg, and then 300 mg, once a week for 4 weeks each) or injections of saline placebo, once a week, for 12 weeks. Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration at day 85 or 99 in the per-protocol population (participants who received more than six doses of study drug) and safety and tolerability in the safety population. In a phase 1/2a first-in-man trial, we assessed the effect of IONIS-APO(a)-LRx, a ligand conjugated antisense oligonucleotide designed to be highly and selectively taken up by hepatocytes, at the BioPharma Services phase 1 unit (Toronto, ON, Canada). Healthy volunteers (Lp[a] >=75 nmol/L) were randomly assigned to receive a single dose of 10-120 mg IONIS-APO(a)LRx subcutaneously in an ascending-dose design or placebo (in a 3:1 ratio; single-ascending-dose phase), or multiple doses of 10 mg, 20 mg, or 40 mg IONIS-APO(a)LRx subcutaneously in an ascending-dose design or placebo (in an 8:2 ratio) at day 1, 3, 5, 8, 15, and 22 (multiple-ascending-dose phase). Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration, safety, and tolerability at day 30 in the single-ascending-dose phase and day 36 in the multiple-ascending-dose phase in participants who were randomised and received at least one dose of study drug. In both trials, the randomised allocation sequence was generated by Ionis Biometrics or external vendor with a permuted-block randomisation method. Participants, investigators, sponsor personnel, and clinical research organisation staff who analysed the data were all masked to the treatment assignments. Both trials are registered with ClinicalTrials.gov, numbers NCT02160899 and NCT02414594. FINDINGS: From June 25, 2014, to Nov 18, 2015, we enrolled 64 participants to the phase 2 trial (51 in cohort A and 13 in cohort B). 35 were randomly assigned to IONIS-APO(a)Rx and 29 to placebo. At day 85/99, participants assigned to IONIS-APO(a)Rx had mean Lp(a) reductions of 66.8% (SD 20.6) in cohort A and 71.6% (13.0) in cohort B (both p<0.0001 vs pooled placebo). From April 15, 2015, to Jan 11, 2016, we enrolled 58 healthy volunteers to the phase 1/2a trial of IONIS-APO(a)-LRx. Of 28 participants in the single-ascending-dose phase, three were randomly assigned to 10 mg, three to 20 mg, three to 40 mg, six to 80 mg, six to 120 mg, and seven to placebo. Of 30 participants in the multiple-ascending-dose phase, eight were randomly assigned to 10 mg, eight to 20 mg, eight to 40 mg, and six to placebo. Significant dose-dependent reductions in mean Lp(a) concentrations were noted in all single-dose IONIS-APO(a)-LRx groups at day 30. In the multidose groups, IONIS APO(a)-LRx resulted in mean reductions in Lp(a) of 66% (SD 21.8) in the 10 mg group, 80% (SD 13.7%) in the 20 mg group, and 92% (6.5) in the 40 mg group (p=0.0007 for all vs placebo) at day 36. Both antisense oligonucleotides were safe. There were two serious adverse events (myocardial infarctions) in the IONIS APO(a)Rx phase 2 trial, one in the IONIS-APO(a)Rx and one in the placebo group, but neither were thought to be treatment related. 12% of injections with IONIS APO(a)Rx were associated with injection-site reactions. IONIS-APO(a)-LRx was associated with no injection-site reactions. INTERPRETATION: IONIS-APO(a)-LRx is a novel, tolerable, potent therapy to reduce Lp(a) concentrations. IONIS-APO(a) LRx might mitigate Lp(a)-mediated cardiovascular risk and is being developed for patients with elevated Lp(a) concentrations with existing cardiovascular disease or calcific aortic valve stenosis. FUNDING: Ionis Pharmaceuticals. PMID- 27665231 TI - Using farmers' attitude and social pressures to design voluntary Bluetongue vaccination strategies. AB - Understanding the context and drivers of farmers' decision-making is critical to designing successful voluntary disease control interventions. This study uses a questionnaire based on the Reasoned Action Approach framework to assess the determinants of farmers' intention to participate in a hypothetical reactive vaccination scheme against Bluetongue. Results suggest that farmers' attitude and social pressures best explained intention. A mix of policy instruments can be used in a complementary way to motivate voluntary vaccination based on the finding that participation is influenced by both internal and external motivation. Next to informational and incentive-based instruments, social pressures, which stem from different type of perceived norms, can spur farmers' vaccination behaviour and serve as catalysts in voluntary vaccination schemes. PMID- 27665232 TI - Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) style diet, and metabolic health in U.S. adults. AB - BACKGROUND & AIMS: There is sparse evidence on the relationship between the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) style diet, and metabolic health, especially comparing cardiometabolic phenotypes among in normal weight and obese populations. We aimed to investigate the association of the Mediterranean diet scores (MDS) and DASH index with metabolically healthy obese (MHO) and metabolically obese normal weight (MONW) phenotypes in a representative U.S. POPULATION: METHODS: MDS and DASH index were calculated using dietary data from 2767 adults aged 20-90 years without any prior diagnosis of cancer or cardiovascular disease from the National Health and Nutrition Examination Survey III, 1988-1994. MHO and MONW individuals were identified using fasting glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein, and high-density lipoprotein-cholesterol. RESULTS: Higher MDS was associated with higher odds of MHO phenotype (odds ratio (OR)T3 vs T1, 2.57 [95% confidence interval (CI), 1.04-6.35]; P trend = 0.04), and higher DASH index was associated with lower odds of MONW phenotype (ORT3 vs T1, 0.59 [95% CI, 0.38 0.93]; P trend = 0.03) only in the younger age group (<45 years for men or premenopausal women). No significant associations of MDS and DASH index with MHO and MONW phenotypes were observed in the older age group (>=45 years for men or postmenopausal women). CONCLUSIONS: Adherence to Mediterranean diet or DASH style diet was favorably associated with MHO and MONW phenotypes only in the younger age group, suggesting that potential dietary intervention to prevent cardiometabolic disease differ by age group. PMID- 27665233 TI - Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease. AB - OBJECTIVE: Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3 deficient mice. METHODS: Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1beta, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1beta, IL 18, and IL-6 production and caspase-1 activity in peritoneal macrophages. RESULTS: Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1beta, pro-IL-18, and RANKL; production of IL-1beta, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice. CONCLUSIONS: Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation. PMID- 27665234 TI - Submillisievert Radiation Dose Coronary CT Angiography: Clinical Impact of the Knowledge-Based Iterative Model Reconstruction. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the noise and image quality of images reconstructed with a knowledge-based iterative model reconstruction (knowledge-based IMR) in ultra-low dose cardiac computed tomography (CT). MATERIALS AND METHODS: We performed submillisievert radiation dose coronary CT angiography on 43 patients. We also performed a phantom study to evaluate the influence of object size with the automatic exposure control phantom. We reconstructed clinical and phantom studies with filtered back projection (FBP), hybrid iterative reconstruction (hybrid IR), and knowledge based IMR. We measured effective dose of patients and compared CT number, image noise, and contrast noise ratio in ascending aorta of each reconstruction technique. We compared the relationship between image noise and body mass index for the clinical study, and object size for phantom study. RESULTS: The mean effective dose was 0.98 +/- 0.25 mSv. The image noise of knowledge-based IMR images was significantly lower than those of FBP and hybrid IR images (knowledge based IMR: 19.4 +/- 2.8; FBP: 126.7 +/- 35.0; hybrid IR: 48.8 +/- 12.8, respectively) (P < .01). The contrast noise ratio of knowledge-based IMR images was significantly higher than those of FBP and hybrid IR images (knowledge-based IMR: 29.1 +/- 5.4; FBP: 4.6 +/- 1.3; hybrid IR: 13.1 +/- 3.5, respectively) (P < .01). There were moderate correlations between image noise and body mass index in FBP (r = 0.57, P < .01) and hybrid IR techniques (r = 0.42, P < .01); however, these correlations were weak in knowledge-based IMR (r = 0.27, P < .01). CONCLUSION: Compared to FBP and hybrid IR, the knowledge-based IMR offers significant noise reduction and improvement in image quality in submillisievert radiation dose cardiac CT. PMID- 27665237 TI - Educating Radiologists About Pain in Radiology. PMID- 27665235 TI - Whole-Lesion Apparent Diffusion Coefficient-Based Entropy-Related Parameters for Characterizing Cervical Cancers: Initial Findings. AB - RATIONALE AND OBJECTIVES: This study aimed to develop whole-lesion apparent diffusion coefficient (ADC)-based entropy-related parameters of cervical cancer to preliminarily assess intratumoral heterogeneity of this lesion in comparison to adjacent normal cervical tissues. MATERIALS AND METHODS: A total of 51 women (mean age, 49 years) with cervical cancers confirmed by biopsy underwent 3-T pelvic diffusion-weighted magnetic resonance imaging with b values of 0 and 800 s/mm2 prospectively. ADC-based entropy-related parameters including first-order entropy and second-order entropies were derived from the whole tumor volume as well as adjacent normal cervical tissues. Intraclass correlation coefficient, Wilcoxon test with Bonferroni correction, Kruskal-Wallis test, and receiver operating characteristic curve were used for statistical analysis. RESULTS: All the parameters showed excellent interobserver agreement (all intraclass correlation coefficients > 0.900). Entropy, entropy(H)0, entropy(H)45, entropy(H)90, entropy(H)135, and entropy(H)mean were significantly higher, whereas entropy(H)range and entropy(H)std were significantly lower in cervical cancers compared to adjacent normal cervical tissues (all P <.0001). Kruskal Wallis test showed that there were no significant differences among the values of various second-order entropies including entropy(H)0, entropy(H)45, entropy(H)90, entropy(H)135, and entropy(H)mean. All second-order entropies had larger area under the receiver operating characteristic curve than first-order entropy in differentiating cervical cancers from adjacent normal cervical tissues. Further, entropy(H)45, entropy(H)90, entropy(H)135, and entropy(H)mean had the same largest area under the receiver operating characteristic curve of 0.867. CONCLUSION: Whole-lesion ADC-based entropy-related parameters of cervical cancers were developed successfully, which showed initial potential in characterizing intratumoral heterogeneity in comparison to adjacent normal cervical tissues. PMID- 27665236 TI - Long-Term Performance of Readers Trained in Grading Crohn Disease Activity Using MRI. AB - RATIONALE AND OBJECTIVES: We aim to evaluate the long-term performance of readers who had participated in previous magnetic resonance imaging (MRI) reader training in grading Crohn disease activity. MATERIALS AND METHODS: Fourteen readers (8 women; 12 radiologists, 2 residents; mean age 40; range 31-59), who had participated in a previous MRI reader training, participated in a follow-up evaluation after a mean interval of 29 months (range 25-34 months). Follow-up evaluation comprised 25 MRI cases of suspected or known Crohn disease patients with direct feedback; cases were identical to the evaluation set used in the initial reader training (of which readers were unaware). Grading accuracy, overstaging, and understaging were compared between training and follow-up using a consensus score by two experienced abdominal radiologists as the reference standard. RESULTS: In the follow-up evaluation, overall grading accuracy was 73% (95% confidence interval [CI]: 62%-81%), which was comparable to reader training grading accuracy (72%, 95% CI: 61%-80%) (P = .66). Overstaging decreased significantly from 19% (95% CI: 12%-27%) to 13% (95% CI: 8%-21%) between training and follow-up (P = .03), whereas understaging increased significantly from 9% (95% CI: 4%-21%) to 14% (95% CI: 7%-26%) (P < .01). CONCLUSIONS: Readers have consistent long-term accuracy for grading Crohn disease activity after case-based reader training with direct feedback. PMID- 27665238 TI - Flow cytometric sorting of fecal bacteria after in situ hybridization with polynucleotide probes. AB - The gut microbiome represents a key contributor to human physiology, metabolism, immune function, and nutrition. Elucidating the composition and genetics of the gut microbiota under various conditions is essential to understand how microbes function individually and as a community. Metagenomic analyses are increasingly used to study intestinal microbiota. However, for certain scientific questions it is sufficient to examine taxon-specific submetagenomes, covering selected bacterial genera in a targeted manner. Here we established a new variant of fluorescence in situ hybridization (FISH) combined with fluorescence-activated cell sorting (FACS), providing access to the genomes of specific taxa belonging to the complex community of the intestinal microbiota. In contrast to standard oligonucleotide probes, the RNA polynucleotide probe used here, which targets domain III of the 23S rRNA gene, extends the resolution power in environmental samples by increasing signal intensity. Furthermore, cells hybridized with the polynucleotide probe are not subjected to harsh pretreatments, and their genetic information remains intact. The protocol described here was tested on genus specifically labeled cells in various samples, including complex fecal samples from different laboratory mouse types that harbor diverse intestinal microbiota. Specifically, as an example for the protocol described here, RNA polynucleotide probes could be used to label Enterococcus cells for subsequent sorting by flow cytometry. To detect and quantify enterococci in fecal samples prior to enrichment, taxon-specific PCR and qPCR detection systems have been developed. The accessibility of the genomes from taxon-specifically sorted cells for subsequent molecular analyses was demonstrated by amplification of functional genes. PMID- 27665239 TI - Venous drainage map of the liver for complex hepatobiliary surgery and liver transplantation. AB - BACKGROUND: Inflow and outflow patency of the liver parenchyma is required to maximize the metabolic function of the liver. However, the definition and distribution of hepatic venous drainage regions has yet to be reported. The aim of this study was to define major hepatic venous tributaries and investigate the mean drainage volume of each territory. METHODS: Three-dimensional (3D) simulations from the livers of 100 healthy donors were reviewed for living donor liver transplantation to determine the distribution of the significant hepatic venous tributaries and the drainage patterns of each segment. RESULTS: The left hepatic vein (LHV), middle hepatic vein (MHV), and right hepatic vein (RHV) contributed a mean drainage of 20.7%, 32.7%, and 39.6% of the entire liver, respectively. Accessory hepatic veins accounted for remaining 7.0%. The middle right hepatic vein (MRHV) and inferior right hepatic vein (IRHV) accounted for a mean total drainage of 8.0% and 10.6%, respectively, when they present. In addition, major tributaries of hepatic veins were clearly detected, and their typical distributions were described. CONCLUSIONS: Knowledge of hepatic venous territories is necessary for complex hepatobiliary surgery. This "venous drainage map" may provide useful information for complex liver surgery and transplantation. PMID- 27665241 TI - The Beginner's Mind in Leadership. PMID- 27665240 TI - Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification. AB - The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research. PMID- 27665243 TI - Determining Cost-Effectiveness of Total Hip and Knee Arthroplasty Using the Short Form-6D Utility Measure. AB - BACKGROUND: With the implementation of the Patient Protection and Affordable Care Act, cost-effectiveness analyses are becoming increasingly important for resource allocation, and particularly for the justification of costly procedures, such as total knee and total hip arthroplasties (TKAs and THAs). Therefore, using the Short Form-6D (SF-6D) utility values, the purpose of this study was to determine (1) the quality-adjusted life years (QALYs) gained and (2) and the cost effectiveness of undergoing THA and TKA. METHODS: A total of 844 patients (357 men, 487 women) who had a mean age of 65 years (range, 39 to 80 years) underwent primary TKA, and 224 patients who had a mean age of 69 years (range, 44 to 88 years) underwent primary THAs at 7 institutions. The SF-6D values were derived for each patient preoperatively and at 1-year follow-up. QALYs were estimated at 1 year, and lifetime QALYs gained were determined using predicted life-expectancy values, at a discounted rate of 3% per year of life expectancy, to reflect a diminishing gain with time. National-level costs were determined using the 2011 Nationwide Inpatient Sample, and incremental cost-effectiveness ratios (ICER) were deduced for both groups. RESULTS: The preoperative SF-6D values for the THA and TKA cohorts were 0.614 (range, 0.37 to 1) and 0.62 (range, 0.3 to 0.93). Postoperatively, SF-6D values improved significantly at 1 year in both groups. One-year QALYs for TKA and THA were 0.768 and 0.799. Lifetime QALYs gained for the groups were 2.07 and 1.85 (1.39 and 1.34 if discounted at a rate of 3% per year). The estimated ICER for TKA vs baseline presurgery was $43,107 per QALY, and $39,453 per QALY for THA vs baseline presurgery. CONCLUSION: The ICER showed that THA and TKA are cost-effective, compared to the $50,000 USD/QALY threshold for cost-effectiveness, and justify resources allocated to these surgeries. The SF-6D can utilize existing functional outcome data, which makes these cost calculations considerably easier and more feasible for practicing orthopedists. PMID- 27665242 TI - Clinical Cold Welding of the Modular Total Hip Arthroplasty Prosthesis. AB - BACKGROUND: A head that is "clinically cold welded" to a stem is one of the commonest reasons for unplanned removal of the stem. It is not clear which hip designs are at greatest risk of clinical cold welding. METHODS: This was a case control study of consecutively received hip implant retrievals; we chose the design of hip that had the greatest number of truly cold-welded heads (n = 11). For our controls, we chose retrieved hips of the same design but without cold welding of the head (n = 35). We compared the clinical variables between these 2 groups using nonparametric Mann-Whitney tests to investigate the significance of differences between the cold-welded and non-cold-welded groups. RESULTS: The design that most commonly caused cold welding was a combination of a Ti stem and Ti taper: 11 out of 48 (23%) were truly cold welded. Comparison of the clinical data showed that no individual factor could be used to predict this preoperatively with none of the 4 predictors tested showing any significance: (1) time to revision (P = .687), (2) head size (P = .067), (3) patient age at primary (P = .380), and (4) gender (P = .054). CONCLUSION: We have shown that clinical cold welding is most prevalent in Ti-Ti combinations of the stem and taper; approximately 25% of cases received at our center were cold welded. Analysis of clinical variables showed that it is not possible to predict which will be cold welded preoperatively. Surgeons should be aware of this potential complication when revising a Ti-Ti stem/head junction. PMID- 27665244 TI - Fluoroscopically Assisted Radiographs Improve Sensitivity of Detecting Loose Tibial Implants in Revision Total Knee Arthroplasty. AB - BACKGROUND: Fluoroscopically assisted radiographs theoretically improve detection of total knee arthroplasty (TKA) implant loosening by providing a better evaluation of the true implant interface, but their utility has not been well studied. We sought to determine whether fluoroscopically guided radiographs improve the sensitivity, specificity, and interobserver reliability of determining TKA implant loosening compared to standard radiographs. METHODS: Standard anteroposterior and lateral and fluoroscopically assisted radiographs were retrospectively obtained from 60 patients within 6 months before revision TKA. Thirty knees were revised for aseptic loosening and 30 knees for other indications, most commonly instability. The radiographs were randomized. Four reviewers independently determined whether each tibial and femoral component was radiographically loose or stable. Intraoperative determination of implant stability was utilized as the gold standard. RESULTS: Fluoroscopically guided radiographs had a significantly higher sensitivity for detecting tibial component loosening compared to standard radiographs (85.3% vs 74.8%, P = .02). Sensitivity in detecting femoral component loosening was poor overall and not improved by fluoroscopic enhancement compared to standard radiographs (58.8% vs 66.5%, P = .33). Fluoroscopically guided radiographs did not improve the specificity of detecting well-fixed implants in either tibial or femoral components nor affect the mean interobserver reliability over standard radiographs (kappa = 0.58 vs kappa = 0.60, P = .6). CONCLUSION: Fluoroscopically assisted radiographs increased the sensitivity of detecting tibial component loosening over standard radiographs, but this clinical significance is unclear. Fluoroscopically guided radiographs may provide benefit in diagnosing aseptic loosening in select patients with painful TKAs. PMID- 27665245 TI - What Preoperative Radiographic Parameters Are Associated With Increased Medial Release in Total Knee Arthroplasty? AB - BACKGROUND: Preoperative varus deformity of the knee is a common malalignment in patients undergoing primary total knee arthroplasty (TKA). We are unaware of any studies that have correlated how various preoperative radiographic parameters can predict the amount of medial releases performed to achieve optimal coronal alignment and ligamentous balance. METHODS: A retrospective review was performed on 67 patients who required at least a medial tibial reduction osteotomy (MTRO) during primary TKA to achieve coronal balance. This patient population was matched 1:1 to another cohort of TKA patients by age, gender, and body mass index who did not require an MTRO. A radiographic evaluation was used to compare the 2 cohorts. RESULTS: Preoperatively, the MTRO cohort was noted to have significantly increased varus tibiofemoral (86.12 degrees vs 93.43 degrees ), tibial articular surface (85.79 degrees vs 87.54 degrees ), and medial tibial articular surface angles (75.22 degrees vs 85.34 degrees ) compared to the control cohort. The MTRO cohort had 3.13 mm of medial tibial offset and 9.06 mm of lateral joint space opening and the control cohort had 0.09 mm and 4.07 mm, respectively. The medial tibial articular surface angle and lateral joint space widening were statistically associated with the MTRO cohort. The final tibiofemoral angle in the MTRO cohort was 92.43 degrees and was 93.40 degrees in the control cohort. CONCLUSION: The MTRO cohort was noted to have several preoperative radiographic parameters that were significantly different than the control cohort. However, the medial tibial articular surface angle and lateral joint space widening were the only radiographic parameters that were statistically associated with requiring an MTRO. PMID- 27665246 TI - In view of standardization Part 2: Management of challenges in the initial treatment of burn patients in Burn Centers in Germany, Austria and Switzerland. AB - INTRODUCTION: Initial therapy of severe burns in specialized burn trauma centers is a challenging task faced by the treating multi-professional and interdisciplinary team. A lack of consistent operating procedures and varying structural conditions was recently demonstrated in preliminary data of our group. These results raised the question on how specific treatment measures in acute burn care are met in the absence of standardized guidelines. MATERIAL AND METHODS: A specific questionnaire containing 57 multiple-choice questions was sent to all 22 major burn centers in Germany, Austria and Switzerland. The survey included standards of airway management and ventilation, fluid management and circulation, body temperature monitoring and management, topical burn wound treatment and a microbiological surveillance. Additionally, the distribution of standardized course systems was covered. RESULTS: 17 out of 22 questionnaires (77%) were returned completed. Regarding volume resuscitation, results showed a similar approach in estimating initial fluid while discrepancies persisted in the use of colloidal fluid and human albumin. Elective tracheostomy and the need for bronchoscopy with suspected inhalation injury were the most controversial issues revealed by the survey. Topical treatment of burned body surface also followed different principles regarding the use of synthetic epidermal skin substitutes or enzymatic wound debridement. Less discrepancy was found in basic diagnostic measures, body temperature management, estimation of the extent of burns and microbiological surveillance. CONCLUSION: While many burn-related issues are clearly not questionable and managed in a similar way in most participating facilities, we were able to show that the most contentious issues in burn trauma management involve initial volume resuscitation, management of inhalation trauma and topical burn wound treatment. Further research is required to address these topics and evaluate a potential superiority of a regime in order to increase the level of evidence. PMID- 27665247 TI - Multimodal impairment-based physical therapy for the treatment of patients with post-concussion syndrome: A retrospective analysis on safety and feasibility. AB - OBJECTIVE: Demonstrate implementation, safety and feasibility of multimodal, impairment-based physical therapy (PT) combining vestibular/oculomotor and cervical rehabilitation with sub-symptom threshold exercise for the treatment of patients with post-concussion syndrome (PCS). SETTING: University hospital outpatient sports medicine facility. PARTICIPANTS: Twenty-five patients (12-20 years old) meeting World Health Organization criteria for PCS following sport related concussion referred for supervised PT consisting of sub-symptom cardiovascular exercise, vestibular/oculomotor and cervical spine rehabilitation. DESIGN: Retrospective cohort. MAIN MEASURES: Post-Concussion Symptom Scale (PCSS) total score, maximum symptom-free heart rate (SFHR) during graded exercise testing (GXT), GXT duration, balance error scoring system (BESS) score, and number of adverse events. RESULTS: Patients demonstrated a statistically significant decreasing trend (p < 0.01) for total PCSS scores (pre-PT M = 18.2 (SD = 14.2), post-PT M = 9.1 (SD = 10.8), n = 25). Maximum SFHR achieved on GXT increased 23% (p < 0.01, n = 14), and BESS errors decreased 52% (p < 0.01, n = 13). Two patients reported mild symptom exacerbation with aerobic exercise at home, attenuated by adjustment of the home exercise program. CONCLUSIONS: Multimodal, impairment-based PT is safe and associated with diminishing PCS symptoms. This establishes feasibility for future clinical trials to determine viable treatment approaches to reduce symptoms and improve function while avoiding negative repercussions of physical inactivity and premature return to full activity. PMID- 27665248 TI - The identification of risk factors for ankle sprains sustained during netball participation. AB - OBJECTIVES: Ankle sprains account for a large percentage of injuries sustained in netball. The identification of risk factors for ankle sprain is the preliminary action required to inform future prevention strategies. DESIGN: Prospective study. PARTICIPANTS: Ninety-four netball players from club and inter-district teams. METHODS: Preseason data were collected for; vertical jump height, perceived ankle instability, sprain history, arthrometry inversion-eversion angles, star excursion balance test reach distances, the number of foot lifts during unilateral stance and demi-pointe balance test results. Participants were followed for the duration of one netball season and ankle sprains were recorded. RESULTS: Eleven sprains were recorded for eleven players using a time-loss definition of injury. Ankle sprains occurred at an incidence rate of 1.74/1000 h of netball exposure. One risk factor was identified to increase the odds of sustaining an ankle sprain during netball participation - a reach distance in the posterior-medial direction of the star excursion balance test of less than or equal to 77.5% of leg length (OR = 4.04, 95% CI = 1.00-16.35). CONCLUSIONS: The identified risk factor can be easily measured and should be considered for preseason injury risk profiling of netball players. Netball players may benefit from training programs aimed at improving single leg balance. PMID- 27665249 TI - Intra-rater reliability and agreement of various methods of measurement to assess dorsiflexion in the Weight Bearing Dorsiflexion Lunge Test (WBLT) among female athletes. AB - OBJECTIVES: To examine the intra-observer reliability and agreement between five methods of measurement for dorsiflexion during Weight Bearing Dorsiflexion Lunge Test and to assess the degree of agreement between three methods in female athletes. DESIGN: Repeated measurements study design. SETTING: Volleyball club. PARTICIPANTS: Twenty-five volleyball players. MAIN OUTCOME MEASUREMENTS: Dorsiflexion was evaluated using five methods: heel-wall distance, first toe-wall distance, inclinometer at tibia, inclinometer at Achilles tendon and the dorsiflexion angle obtained by a simple trigonometric function. For the statistical analysis, agreement was studied using the Bland-Altman method, the Standard Error of Measurement and the Minimum Detectable Change. Reliability analysis was performed using the Intraclass Correlation Coefficient. RESULTS: Measurement methods using the inclinometer had more than 6 degrees of measurement error. The angle calculated by trigonometric function had 3.28 degrees error. The reliability of inclinometer based methods had ICC values < 0.90. Distance based methods and trigonometric angle measurement had an ICC values > 0.90. Concerning the agreement between methods, there was from 1.93 degrees to 14.42 degrees bias, and from 4.24 degrees to 7.96 degrees random error. CONCLUSION: To assess DF angle in WBLT, the angle calculated by a trigonometric function is the most repeatable method. The methods of measurement cannot be used interchangeably. PMID- 27665250 TI - Association between ambient air pollution and proliferation of umbilical cord blood cells. AB - It has been established as a common knowledge that ambient air pollution (AAP) has an adverse effect on human health. The pathophysiological mechanism of this impact is likely to be related to the oxidative stress. In the current study we estimate the association between AAP and cell proliferation (CP) of umbilical cord blood cells, representing maternal organism most proximal to the fetal body. Blood samples were tested for proliferation in 292 enrolled Arab-Bedouin women at delivery (July 2012-March 2013). The estimates of AAP were defined by a hybrid satellite based model predicting both PM2.5 (particles<2.5um in diameter) and PM10 (particles<10um in diameter) as well as monitoring stations for gaseous air pollutants. Risk estimates of pollution exposure were adjusted to medical history, household risk factors and meteorological factors on the day of delivery or one week prior. Ambient ozone (O3) levels on 1, 2, 3and 4 days prior to delivery were associated with lower CP (Prevalence ratio (PR)=0.92, 0.92, 0.93, 0.93, respectively). Increase in inter-quartile range (IOR) of PM2.5 one day before delivery was associated with 9% increase in CP levels (PR=1.09). The positive direction in association was changed to negative association with CP for PM2.5 levels measured at more distant time periods (PR=0.90 and 0.93 for lags 5 and 6 days, respectively). Investigation of PM10 levels indicated a similar pattern (PR=1.05 for pollution values recorded one day before delivery and 0.93 and 0.95 for lags of 5 and 6 days, respectively). Carbon monoxide (CO) levels were associated with lower CP on the day of delivery and 1day prior (PR=0.92 and PR=0.94). To conclude, the levels of cell proliferation of umbilical cord blood cells appear to be associated with the AAP. More studies are needed to support our findings. PMID- 27665251 TI - [How I do... laparoscopic insertion of a silicone fluted drain?] PMID- 27665228 TI - Measuring the health-related Sustainable Development Goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 2015. AB - BACKGROUND: In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). METHODS: We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. FINDINGS: In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r2=0.88) and the MDG index (r2=0.92), whereas the non-MDG index had a weaker relation with SDI (r2=0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. INTERPRETATION: GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs. FUNDING: Bill & Melinda Gates Foundation. PMID- 27665252 TI - In vitro fertilization outcomes after ablation of endometriomas using plasma energy: A retrospective case-control study. AB - OBJECTIVE: Ovarian endometrioma ablation using plasma energy appears to be a valuable alternative to cystectomy, because it could spare underlying ovarian parenchyma resulting in high spontaneous and overall pregnancy rates. After initial postoperative decrease, anti-mullerian hormone (AMH) level progressively increases several months after ablation. The aim of our study was to assess the outcomes of in vitro fertilization (IVF) in women managed for ovarian endometriomas by ablation using plasma energy, when compared to those in women free of endometriosis. METHODS: Retrospective preliminary case-control study, enrolling women undergoing IVF or IntraCytoplasmic Sperm Injection (ICSI), from July 2009 to December 2014. Cases were infertile women with previous ovarian endometrioma ablation using plasma energy and were matched by age, AMH level and assisted reproductive technique with controls presumed free of endometriosis. IVF/ICSI response (type of protocol, dose of gonadotrophin, number of oocytes, fertilization rate) and outcomes were compared between the two groups. RESULTS: In all, 37 cases were compared to 74 controls. Age (30.9+/-4.4 years vs. 31.7+/ 4.2 years), AMH level (2.8+/-2ng/mL vs. 2.8+/-1.7ng/mL) and ART procedures (ICSI in 24.3% vs. 27%) were comparable between the two groups. Of the 37 cases, previous surgical procedures on right and left ovaries were performed in 27% and 21.6% of patients respectively, 81% of patients were nullipara. AFSr score was 73+/-41, while deep endometriosis infiltrated the rectum and the sigmoid colon in respectively 40.5% and 27% of patients. Despite a lower number of oocytes retrieved, cases presented better implantation rate, pregnancy and delivery rates per cycle, oocyte retrieval, transfer, and embryo, as well as superior cumulative birth rate per transfer. CONCLUSION: Ovarian endometrioma ablation using plasma energy is followed by good IVF/ICSI outcomes, suggesting that surgical procedure spares underlying ovarian parenchyma. These results consolidate those of previous studies reporting high spontaneous conception rate. Hence, ovarian endometrioma ablation using plasma energy appears to be a valuable alternative to cystectomy in patients presenting with endometriosis and pregnancy intention. PMID- 27665253 TI - Progression of coronary artery calcification is stronger in poorly than in well controlled diabetes: Results from the Heinz Nixdorf Recall Study. AB - AIM: To assess associations between HbA1c and progression of coronary artery calcification (CAC) in persons with and without diabetes. METHODS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany (N=3453, aged 45 74years), CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. At baseline, participants were divided into five groups: poorly (HbA1c>=7.0%) and well (HbA1c<7.0%) controlled previously known diabetes (group I/II); no previously known diabetes with HbA1c >=6.5% (group III), HbA1c 5.7-6.4% (group IV), and HbA1c <5.7% (group V). We fitted linear, logistic and robust Poisson regression models to assess associations between diabetes group and PF5 (factor by which CAC after 5-year follow-up is larger than baseline CAC), and categories of CAC change, respectively. RESULTS: Relative to group V, adjusted percentage increase of the geometric mean of PF5 (95% CI) was: 69.1% (33.9%;113.6%), 15.4% (-5.6%;41.1%), -4.1% (-22.2%;18.2%), 4.2% (-5.4%;14.8%) for groups I-IV, respectively. The corresponding odds ratios for annual CAC increase >=100 Agatston units (reference: <10) were 10.0 (4.8;20.6), 4.0 (2.1;7.6), 1.5 (0.7;3.2), and 1.1 (0.7;1.8). CONCLUSIONS: In known diabetes, CAC progression was stronger in poor diabetes control. For newly detected diabetes diagnosed by HbA1c >=6.5%, associations with CAC progression were weak. PMID- 27665254 TI - Estimating the burden of disease attributable to injecting drug use as a risk factor for HIV, hepatitis C, and hepatitis B: findings from the Global Burden of Disease Study 2013. AB - BACKGROUND: Previous estimates of the burden of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) among people who inject drugs have not included estimates of the burden attributable to the consequences of past injecting. We aimed to provide these estimates as part of the Global Burden of Disease (GBD) Study 2013. METHODS: We modelled the burden of HBV and HCV (including cirrhosis and liver cancer burden) and HIV at the country, regional, and global level. We extracted United Nations data on the proportion of notified HIV cases by transmission route, and estimated the contribution of injecting drug use (IDU) to HBV and HCV disease burden by use of a cohort method that recalibrated individuals' history of IDU, and accumulated risk of HBV and HCV due to IDU. We estimated data on current IDU from a meta-analysis of HBV and HCV incidence among injecting drug users and country-level data on the incidence of HBV and HCV between 1990 and 2013. We calculated estimates of burden of disease through years of life lost (YLL), years of life lived with disability (YLD), deaths, and disability-adjusted life-years (DALYs), with 95% uncertainty intervals (UIs) calculated for each metric. FINDINGS: In 2013, an estimated 10.08 million DALYs were attributable to previous exposure to HIV, HBV, and HCV via IDU, a four-times increase since 1990. In total in 2013, IDU was estimated to cause 4.0% (2.82 million DALYs, 95% UI 2.4 million to 3.8 million) of DALYs due to HIV, 1.1% (216 000, 101 000-338 000) of DALYs due to HBV, and 39.1% (7.05 million, 5.88 million to 8.15 million) of DALYs due to HCV. IDU-attributable HIV burden was highest in low-to-middle-income countries, and IDU-attributable HCV burden was highest in high-income countries. INTERPRETATION: IDU is a major contributor to the global burden of disease. Effective interventions to prevent and treat these important causes of health burden need to be scaled up. FUNDING: Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council. PMID- 27665255 TI - Social Desirability Trait Is Associated with Self-Reported Vegetable Intake among Women Enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children. AB - BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Fresh Start (WFS) is a randomized controlled trial of nutrition education to promote farmers' market fruit and vegetable (F/V) purchases and consumption among women enrolled in WIC. OBJECTIVES: Using baseline data from WFS to examine associations between social desirability trait, the tendency to respond in a manner consistent with expected norms, and self-reported F/V intake and to determine whether associations, if found, are moderated by participant characteristics. DESIGN: Cross-sectional. PARTICIPANTS/SETTING: Seven hundred forty-four women enrolled in WFS. The setting is a New Jersey-based WIC agency located in a densely populated urban area. MEASURES: Items assessing participant characteristics, a short form of the Marlowe-Crowne Social Desirability Scale, and validated measures of the frequency and quantity of F/V intake. STATISTICAL ANALYSES: Linear regression analysis to examine associations between social desirability trait and F/V intake and hierarchical regression analysis to test for moderation by participant characteristics of the associations between social desirability trait and F/V intake. RESULTS: Social desirability trait was significantly associated with times per day vegetables were reported to have been consumed (beta=0.08, P=0.03). The association was moderated by breastfeeding status. Among breastfeeding women, social desirability trait was unrelated to reported intake, whereas among non-breastfeeding women, it was positively associated with intake (a 1-unit increase in the social desirability score was associated with a 0.12 increase in times per day vegetables were reported to have been consumed). CONCLUSIONS: Social desirability trait is associated with self reported vegetable intake among WIC participants generally and non-breastfeeding participants in particular and should be assessed in these groups. Replication studies with comparative measures of "true intake" are needed to determine whether social desirability trait biases self-reports of vegetable intake or whether those with a high social desirability trait consume vegetables more often. PMID- 27665256 TI - Social Desirability Trait: Biaser or Driver of Self-Reported Dietary Intake? PMID- 27665258 TI - Mobile phone use, behavioural problems and concentration capacity in adolescents: A prospective study. AB - The aim of this study is to prospectively investigate whether exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones and other wireless communication devices is related to behavioural problems or concentration capacity in adolescents. The HERMES (Health Effects Related to Mobile phonE use in adolescentS) study sample consisted of 439 Swiss adolescents aged 12-17 years. Behavioural problems were assessed using the Strengths and Difficulties Questionnaire (SDQ), concentration capacity of the adolescents was measured by means of a standardized computerized cognitive test named FAKT. Cross sectional and longitudinal (1year of follow-up) analyses were performed to investigate possible associations between behavioural problems and concentration capacity and different exposure measures: self-reported and operator-recorded wireless communication device use, cumulative RF-EMF brain and whole body dose and measured personal RF-EMF exposure. In the cross-sectional analyses behavioural problems were associated with several self-reported wireless device use measures but not operator-recorded mobile phone use measures, concentration capacity was associated with several self-reported and operator-recorded exposures. The longitudinal analyses point towards absence of associations. The lack of consistent exposure-response patterns in the longitudinal analyses suggests that behavioural problems and concentration capacity are not affected by the use of wireless communication devices or RF-EMF exposure. Information bias and reverse causality are likely explanations for the observed cross-sectional findings. PMID- 27665257 TI - Cortical thickness of neural substrates supporting cognitive empathy in individuals with schizophrenia. AB - BACKGROUND: Cognitive empathy is supported by the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. METHODS: 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. RESULTS: Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p<0.05) and impaired cognitive empathy across all measures (all p<0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p<0.05) was related to cognitive empathy in controls, we did not observe these relationships in individuals with schizophrenia (all p>0.10). CONCLUSIONS: Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia. PMID- 27665259 TI - Preoperative Anemia and Low Hemoglobin Level Are Associated With Worse Clinical Outcomes in Patients With Bladder Cancer Undergoing Radical Cystectomy: A Meta Analysis. AB - PURPOSE: The aim of this study was to determine the effect of preoperative anemia status and hemoglobin level on clinical outcomes in patients with bladder cancer undergoing radical cystectomy. MATERIALS AND METHODS: A systematic review of literature with meta-analyses of predefined outcomes based on a search of PubMed and EMBASE was performed. Hazard ratios (HRs) measuring the association between preoperative anemia/hemoglobin and all-cause mortality, cancer-specific mortality, and disease recurrence were calculated with random effects model. Study heterogeneities were quantified by I2 tests. Publication bias was assessed with funnel plots. RESULTS: A total of 17 studies evaluating the impact of preoperative anemia status (categorical, 11 studies) and hemoglobin level (continuous, 7 studies) on clinical outcomes were included. The cutoff value of anemia varied among studies (10.5-13.5 g/dL for male, 10.5-13.4 g/dL for female). Meta-analyses showed that compared with non-anemia, anemia was associated with increased all-cause mortality (HR, 1.75; 95% confidence interval [CI], 1.48-2.05; P < .00001; I2 = 30%), cancer-specific mortality (HR, 1.80; 95% CI, 1.45-2.25; P < .00001; I2 = 26%), and disease recurrence (HR, 1.37; 95% CI, 1.16-1.62; P = .0002; I2 = 9%). Meta-analyses showed that higher level of hemoglobin was associated with decreased all-cause mortality (HR, 0.90; 95% CI, 0.87-0.92; P < .00001; I2 = 13%), cancer-specific mortality (HR, 0.90; 95% CI, 0.85-0.95; P = .0003; I2 = 61%), and disease recurrence (HR, 0.95; 95% CI, 0.91-0.99; P = .01; I2 = 53%). No obvious publication bias was observed. CONCLUSIONS: Preoperative anemia and low hemoglobin level are associated with earlier recurrence and shorter survival of patients with bladder cancer undergoing radical cystectomy. However, well-designed prospective studies with large sample size and limited confounding factors are needed to confirm and update our findings. PMID- 27665260 TI - A multicenter study of blood component transfusion in patients with liver cirrhosis in China: Patient characteristics, transfusion practice, and outcomes. AB - BACKGROUND: Cirrhosis is a complex acquired disorder of hemostasis and patients frequently receive blood transfusions. But there is very limited data on patterns of blood use at a patient level. AIMS: To characterize blood use in cirrhotic patients in China and compare with recommendations to help identify areas where quality improvement strategies can be targeted. We also compared findings to a similar study undertaken in UK. METHODS: A cross-sectional study was conducted in 11 hospitals over a 2-month period. Data were collected prospectively on each hospitalized cirrhotic patient to day 28. RESULTS: 1595 cirrhotic patients were included and 20.6% were transfused. 48.2% of transfused patients received transfusion for bleeding, most commonly gastrointestinal bleeding (65.8%). The remaining 51.8% were transfused for non-bleeding indications. 32.5% of patients transfused for gastrointestinal bleeding with red blood cells had a pre transfusion haemoglobin >7g/dL. 89.1% of patients transfused frozen plasma for non-bleeding indications received them in the absence of a planned procedure. The patterns of blood transfusion in cirrhosis were different between China and UK. Of note, empirical prophylactic use of frozen plasma was more common in the Chinese study (89%) than in the UK (24%). CONCLUSION: Education and research should be implemented to improve patient blood management, especially in prophylactic frozen plasma use area. PMID- 27665261 TI - Implementation and adherence to osteoporosis screening guidelines among coeliac disease patients. AB - BACKGROUND: There are no studies evaluating the implementation of American Gastroenterological Association (AGA) guidelines on osteoporosis screening in coeliac disease. AIMS: To investigate implementation of osteoporosis screening guidelines in coeliac disease patients and determine how often bone mineral density (BMD) assessment leads to therapeutic intervention. METHODS: We screened all patients with biopsy-proven coeliac disease at our center from 2003 to 2013 and collected data on indication and results of dual energy X-ray absorptiometry scanning (DXA) and therapeutic interventions. RESULTS: Of 222 adults with coeliac, only 80 (36%) underwent DXA after their diagnosis. Of those, 43 had DXA for osteoporosis screening specifically related to their coeliac diagnosis. Of these 43 patients, 28 (65.1%) had low BMD. A therapeutic intervention was made in the majority of these patients (21/28, 75%). Of 330 pediatric coeliac cases, 52 (15.8%) had DXA specifically in the context of the coeliac disease diagnosis with only 5 being complicated coeliac disease. Of these, 3 (5.8%) had low BMD and only 2 underwent therapeutic intervention. CONCLUSIONS: Osteoporosis screening guidelines are not followed in the majority of patients with coeliac disease but, when followed, frequently lead to therapeutic intervention. Osteoporosis screening guidelines in coeliac disease need to be updated, strengthened and publicized. PMID- 27665262 TI - Endoscopic ultrasonography-guided drainage combined with trans-duodenoscope cyclic irrigation technique for walled-off pancreatic necrosis. AB - BACKGROUND: Endoscopic ultrasonography-guided drainage has been established as a good treatment modality in the management of walled-off pancreatic necrosis, but the unmanageable infection of postoperation is still a thorny problem due to the poor drainage ability for solid necrotic debris only through transmural stent and nasocystic catheter. AIMS: Introduce a novel therapeutic method, namely endoscopic ultrasonography-guided drainage combined with cyclic irrigation technique in managing patients with walled-off pancreatic necrosis. METHODS: 18 patients with severe acute pancreatitis complicated with walled-off pancreatic necrosis received treatment with endoscopic ultrasonography-guided drainage combined with cyclic irrigation were involved in this retrospective study. RESULTS: 17 of 18 patients with walled-off pancreatic necrosis were treated by this new therapeutic method. Subsequent surgery was performed in 1 case due to uncontrolled infection, complications such as perforation, bleeding or multiple organ failure were not observed. Treatment success rate was high (16 in 17, 94.12%). CONCLUSION: Endoscopic ultrasonography-guided drainage combined with cyclic irrigation is an effective treatment option for symptomatic walled-off pancreatic necrosis to facilitate drainage and obviate the need for subsequent surgery or endoscopic necrosectomy. PMID- 27665263 TI - Frequency of thiopurine methyltransferase mutation in patients of Mediterranean area with inflammatory bowel disease and autoimmune disorders. AB - BACKGROUND AND AIMS: Few studies exist on the frequency of thiopurine methyltransferase (TPMT) mutation in patients from Southern Europe. We aimed to evaluate the frequency of TPMT mutation in a homogeneous Sicilian cohort of patients with inflammatory bowel disease (IBD), autoimmune and hematological disorders, the rate of thiopurine-related adverse events, and its association with the TPMT genotype. RESULTS: Among 105 patients with IBD, 45 with autoimmune disease, and 34 with hematologic diseases, the homozygous TPMT variant genotype was found in one patient only (0.5%), while the heterozygous TPMT genotype was identified in 8 patients (4.3%). In patients with IBD, leukopenia was observed in ten patients: one had the homozygous TPMT genotype, one the heterozygous genotype, and the remaining eight the wild type genotype. CONCLUSIONS: The frequency of TPMT mutation in a Mediterranean area was low. TPMT genotyping is not a sensitive tool for predicting thiopurine-induced leukopenia. PMID- 27665264 TI - Molecular analysis reveals the diversity of Hepatozoon species naturally infecting domestic dogs in a northern region of Brazil. AB - This study aimed to optimize molecular methods for detecting DNA of Hepatozoon spp. as well as identify the phylogenetic relationships of Hepatozoon strains naturally infecting domestic dogs in Belem, Para, northern Brazil. Blood samples were collected from 138 dogs, and screened for Hepatozoon spp. using a new nested PCR assay. Positive samples were subjected to genetic characterization based on amplification and sequencing of approximately 670bp of the Hepatozoon spp. 18S rRNA. Of the positive dogs, four shared the haplotype Belem 01, one dog presented the haplotype Belem 02 and two dogs shared the haplotype Belem 03. A Bayesian inference indicates that haplotypes Belem 01 and Belem 02 are phylogenetically related to H. canis, while Belem 03 is related to H. americanum. Overall, based on the first molecular evidence of H. americanum in Brazilian domestic dogs, the proposed protocol may improve the epidemiological investigation of canine hepatozoonosis. PMID- 27665265 TI - Evidence of rapid changes in Lyme disease awareness in Canada. AB - Lyme disease (LD) is emerging in Canada. A key preventive strategy is promoting the adoption by the general public of personal preventive behaviors regarding tick bites. The aim of this study was to measure the changes in public awareness toward ticks and LD before and after the launch of a national communication campaign in Canada using data from two surveys conducted in March and December 2014. The results show a significant increase in awareness of LD after compared to before the campaign, but also suggest that the importance of this increase is not equal amongst Canadian regions. Moreover, respondents whose level of awareness increased most significantly were those who lived in regions with low entomologic risk. The findings underline the importance of risk communications for emerging diseases and reinforce the need to understand the specific characteristics of the targeted populations before the implementation of communication campaigns to increase their efficacy. PMID- 27665266 TI - Matching Speaking to Singing Voices and the Influence of Content. AB - OBJECTIVES AND HYPOTHESIS: We tested whether speaking voices of unfamiliar people could be matched to their singing voices, and, if so, whether the content of the utterances would influence this matching performance. Our hypothesis was that enough acoustic features would remain the same between speaking and singing voices such that their identification as belonging to the same or different individuals would be possible even upon a single hearing. We also hypothesized that the contents of the utterances would influence this identification process such that voices uttering words would be easier to match than those uttering vowels. STUDY DESIGN: We used a within-participant design with blocked stimuli that were counterbalanced using a Latin square design. In one block, mode (speaking vs singing) was manipulated while content was held constant; in another block, content (word vs syllable) was manipulated while mode was held constant, and in the control block, both mode and content were held constant. METHOD: Participants indicated whether the voices in any given pair of utterances belonged to the same person or to different people. RESULTS: Cross-mode matching was above chance level, although mode-congruent performance was better. Further, only speaking voices were easier to match when uttering words. CONCLUSIONS: We can identify speaking and singing voices as the same or different even on just a single hearing. However, content interacts with mode such that words benefit matching of speaking voices but not of singing voices. Results are discussed within an attentional framework. PMID- 27665267 TI - Methods of Fat Tissue Processing for Human Vocal Fold Injection: A Systematic Review. AB - OBJECTIVES: We analyzed different methods used to process autologous fat tissues for vocal fold injection (VFI). VFI is a safe procedure that preserves the folds' original elasticity and vibration properties and rarely triggers foreign-body reactions, but is often a temporary treatment due to fat reabsorption. To avoid it, selecting a technique that provides as many viable implantable adipocytes as possible is mandatory. STUDY DESIGN: This is a systematic review. METHODS: Data were collected from PubMed, Embase, Ovid, and Cochrane Library. Authors systematically reviewed databases for papers on autologous fat tissue processing methods involving human injections in vocal folds and vocalization outcomes that evolved the acoustic analysis of the voice before and after the surgical procedure, independently of the follow-up time. RESULTS: Nine out of the 517 articles met selection criteria for analysis. No standardized technique was found. CONCLUSION: There is no standardized technique for processing fat tissue for vocal fold injection. Further research is needed to point out the best available technique. PMID- 27665268 TI - Distractor-based stimulus-response bindings retrieve decisions independent of motor programs. AB - Research on the distractor response binding (DRB) effect (Frings, Rothermund, & Wentura, 2007) suggests that distractors are integrated with target responses into an event file or stimulus-response (SR) episode. The whole event file is retrieved when the distractor is repeated and as a consequence distractors can retrieve previous responses. Nett, Broder, and Frings (2015) argued that even decisions under uncertainty are integrated into event files and can later on be retrieved by distractors. However, their paradigm did not allow disentangling the retrieval of decisions from the retrieval of motor programs. Here we disentangled the retrieval of decisions and motor programs by assuring that retrieved decisions were not confounded by the repetitions of motor programs. In particular, in two experiments using a sequential prime-probe distractor priming task participants used other keys or other effectors for prime and probe responses; nevertheless repeated task-irrelevant distractors increased the probability that participants repeated the prime decision irrespective of motor programs. Thus, decision features can become part of an event-file and directly be retrieved by irrelevant information suggesting that bindings have an even higher flexibility and ubiquity than previously assumed. PMID- 27665269 TI - Acute viral bronchiolitis and risk of asthma in schoolchildren: analysis of a Brazilian newborn cohort. AB - OBJECTIVE: To verify whether the occurrence of acute viral bronchiolitis in the first year of life constitutes a risk factor for asthma at age 6 considering a parental history of asthma. METHODS: Cross-sectional study in a cohort of live births. A standardized questionnaire of the International Study of Asthma and Allergies in Childhood was applied to the mothers to identify asthma in children at the age of 6 years. Acute viral bronchiolitis diagnosis was performed by maternal report of a medical diagnosis and/or presence of symptoms of coryza accompanied by cough, tachypnea, and dyspnea when participants were 3, 6, 9, and 12 months. Socioeconomic, environmental data, parental history of asthma, and data related to pregnancy were collected in the first 72h of life of the newborn and in prospective home visits by trained interviewers. The association between acute viral bronchiolitis and asthma was evaluated by logistic regression analysis and potential modifier effect of parental history was verified by introducing an interaction term into the adjusted logistic regression model. RESULTS: Prevalence of acute viral bronchiolitis in the first year of life was 68.6% (461). The occurrence of acute viral bronchiolitis was a risk factor for asthma at 6 years of age in children with parental history of asthma OR: 2.66, 95% CI (1.10-6.40), modifier effect p=0.002. Parental history of asthma OR: 2.07, 95% CI (1.29-3.30) and male gender OR: 1.69, 95% CI, (1.06-2.69) were other identified risk factors for asthma. CONCLUSION: Acute viral bronchiolitis in the first year of life is a risk factor for asthma in children with parental history of asthma. PMID- 27665270 TI - Contribution of secondary Igkappa rearrangement to primary immunoglobulin repertoire diversification. AB - Abs reactive to DNA and DNA/histone complexes are a distinguished characteristic of primary immunoglobulin repertoires in autoimmune B6.MRL-Faslpr and MRL/MpJ Faslpr mice. These mice are defective in Fas receptor, which is critical for the apoptosis of autoreactive B cells by an extrinsic pathway. In the present study, we explored the possibility that bone marrow small pre-B and immature B cells from adult B6.MRL-Faslpr mice and MRL/MpJ-Faslpr mice respectively, which contain autoreactive B-cell antigen receptors (BCR) and manifest autoimmune syndromes, exhibit enhanced receptor editing patterns. Indeed, FASlpr pre B and immature B cells were shown to possess more ongoing replacements of non-productive (nP) than productive (P) primary VkappaJkappa rearrangements. Significantly, the P vs nP ratios of these replaced primary rearrangements were 1:2, thus indicating that kappa light-chain production appears not to inhibit secondary rearrangements. In addition, we identified multiple atypical rearrangements, such as Vkappa cRS (cryptic recombination signals) cleavages. These results suggest that the onset of light chain secondary rearrangements persists similarly as a non-selected mode and independent of BCR autoreactivity during certain developmental windows of bone marrow B cells in lupus-prone mice and control, and leads us to propose the function of secondary, de novo Igkappa rearrangements to increase BCR diversity. PMID- 27665272 TI - Old hearts for modern investigations: CT and MR for archaeological human hearts remains. AB - INTRODUCTION: Among 800 burials dated between the 15th and 18th centuries and found in the center of Rennes (Brittany, France), a collection of five heart shaped lead urns was discovered. This material was studied using classical methods (external study, autopsy and histology), and also modern imaging like computed tomography (CT), magnetic resonance (MR) before and after coronary opacification. The aim of this manuscript is to describe different steps of ancient soft tissues study, especially using imaging techniques. METHODS: The study gathered various specialists: anthropologists, archeologists, forensic pathologists, radiologists, pathologic physicians, and physicists. Imaging techniques were performed, before and after coronary opacification. Finally, hearts were autopsied and different histological samples were analyzed. RESULTS: Only heart n degrees 2 was too damaged to be studied. Heart n degrees 3 was considered as normal using all investigation techniques. The study of Hearts n degrees s 4 and 5 revealed dilated cardiomyopathy while Heart n degrees 1 showed important signs of diffuse hypertrophic cardiomyopathy. Different fibro lipid plaques were identified using imaging techniques, and were confirmed by histology. CONCLUSIONS: The study of archeological soft tissues using modern imaging is possible if the material is well-preserved. This type of research can uncover principal findings, allowing scientists to establish diseases of ancient times. PMID- 27665273 TI - Pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: E-cadherin immunoexpression and analysis of the CDH1 -160C/A polymorphism. AB - OBJECTIVE: Despite their similar cellular origin, pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC) present distinct behaviors. This study aimed to analyze the immunoexpression of E-cadherin in PA and ACC of salivary glands, and to investigate differences in its expression in relation to E-cadherin gene (CDH1) -160C/A polymorphism. DESIGN: Twenty-four PA (15 cell-rich and 9 cell-poor tumors) and 24 ACC (10 tubular, 8 cribriform and 6 solid tumors) were selected for the analysis of pattern of distribution, and cellular localization of E cadherin. In addition, E-cadherin expression was evaluated using the H-score scoring system. The CDH1 -160C/A polymorphism was investigated by PCR-RFLP. RESULTS: No significant differences in pattern of distribution (p=0.181) and cellular localization (p=0.192) of E-cadherin were observed between PA and ACC. Comparison of PA and ACC cases revealed a higher median H-score in the latter (p=0.036). Cell-rich PA presented a higher H-score than cell-poor tumors (p=0.013), whereas no significant differences in E-cadherin expression were observed between ACC subtypes (p=0.254). The heterozygous genotype of the CDH1 160C/A polymorphism was detected in only one PA and one ACC. H-scores for tumors carrying the polymorphism were below the lower quartile of their respective groups. CONCLUSIONS: The results suggest that E-cadherin expression in PA and ACC is mainly related to cellular composition (epithelial cells versus myoepithelial cells) and degree of differentiation of myoepithelial cells in these tumors. The CDH1 -160C/A polymorphism does not seem to significantly influence the expression of E-cadherin in PA and ACC of salivary glands. PMID- 27665274 TI - Prevalence of Helicobacter pylori from the oral cavity of Mexican asymptomatic children under 5 years of age through PCR. AB - OBJETIVE: H. pylori infection is acquired early in life, but symptoms occur mainly in adults. The mode of transmission remains unclear, but several studies have demonstrated that the microorganism may be transmitted orally. H. pylori has been detected in the oral cavity of children, and some authors have studied infection prevalence due to the importance of the bacteria in gastric and extragastric pathology. In Mexico, little is known about H. pylori prevalence in the oral cavity of asymptomatic children, so the aims of this study were to estimate the prevalence of H. pylori in asymptomatic children and evaluate factors associated with the infection. DESING: We studied 162 asymptomatic children of 3.025+/-1.474 years of age from a kindergarten in Mexico City. Oral swabs, rotating around to cheeks inside of oral cavity were obtained to determine H. pylori, using the polymerase chain reaction for 16S rRNA and glmM genes. RESULTS: We detected a 13% prevalence of H. pylori infection by PCR, and the results were confirmed by sequencing and showed a >97% identity with H. pylori. We observed increased infection with age. No association between H. pylori infection and variables such as sex, family history of gastric diseases, crowding or pets in the home were found. CONCLUSION: H. pylori infection in the oral cavity is frequent among asymptomatic children in Mexico, which represents a risk of infection for other family members and for other children in educational facilities. Early diagnosis is essential for control of the infection and for the development of preventive strategies in childhood. PMID- 27665271 TI - Nutritional interventions in primary mitochondrial disorders: Developing an evidence base. AB - In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD. PMID- 27665275 TI - Robotic-assisted Nipple Sparing Mastectomy: A feasibility study on cadaveric models. PMID- 27665277 TI - Trajectories of Annual Number of Sexual Partners from Adolescence to Emerging Adulthood: Individual and Family Predictors. AB - Adolescent sexual development is not the same across the board, and can be seen as both normative as well as risky behavior, depending on factors such as age of onset and number of partners. This longitudinal study identified developmental trajectories of annual number of sexual partners from adolescence to emerging adulthood and their antecedents. From the ages of 16-22, 332 participants (60.8 % females) annually reported their number of sexual partners. Measures of adolescent and family characteristics taken at ages 13-15 were used as predictors. Group-based modeling identified four trajectory groups: the abstainers group (9.1 %), low-increasing group (30.6 %), medium-increasing group (53.0 %), and multiple-partners group (7.3 %). Multinomial logistical regressions indicated that better social competence increased chances of belonging to the multiple-partners group as compared to the abstainers and low-increasing groups, and more substance use predicted membership in the multiple-partners group as compared to the abstainers group. Moreover, females were overrepresented in the low-increasing and medium-increasing groups. These results imply a greater diversity in sexual development than proposed in the literature and highlight the importance of identifying the strengths and competencies associated with healthy sexual development along with the early risk factors. PMID- 27665276 TI - Longitudinal Pathways from Cumulative Contextual Risk at Birth to School Functioning in Adolescence: Analysis of Mediation Effects and Gender Moderation. AB - Children and adolescents exposed to multiple contextual risks are more likely to have academic difficulties and externalizing behavior problems than those who experience fewer risks. This study used data from the Northern Finland Birth Cohort 1986 (a population-based study; N = 6961; 51 % female) to investigate (a) the impact of cumulative contextual risk at birth on adolescents' academic performance and misbehavior in school, (b) learning difficulties and/or externalizing behavior problems in childhood as intervening mechanisms in the association of cumulative contextual risk with functioning in adolescence, and (c) potential gender differences in the predictive associations of cumulative contextual risk at birth with functioning in childhood or adolescence. The results of the structural equation modeling analysis suggested that exposure to cumulative contextual risk at birth had negative associations with functioning 16 years later, and academic difficulties and externalizing behavior problems in childhood mediated some of the predictive relations. Gender, however, did not moderate any of the associations. Therefore, the findings of this study have implications for the prevention of learning and conduct problems in youth and future research on the impact of cumulative risk exposure. PMID- 27665278 TI - Prevalence and Correlates of the Perpetration of Cyber Dating Abuse among Early Adolescents. AB - Much is known about the prevalence and correlates of dating violence, especially the perpetration of physical dating violence, among older adolescents. However, relatively little is known about the prevalence and correlates of the perpetration of cyber dating abuse, particularly among early adolescents. In this study, using a predominantly ethnic-minority sample of sixth graders who reported ever having had a boyfriend/girlfriend (n = 424, 44.2 % female), almost 15 % reported perpetrating cyber dating abuse at least once during their lifetime. Furthermore, using a cross-sectional design, across multiple levels of the socio ecological model, the individual-level factors of (a) norms for violence for boys against girls, (b) having a current boyfriend/girlfriend, and (c) participation in bullying perpetration were correlates of the perpetration of cyber dating abuse. Collectively, the findings suggest that dating violence interventions targeting these particular correlates in early adolescents are warranted. Future studies are needed to establish causation and to further investigate the relative importance of correlates of the perpetration of cyber dating abuse among early adolescents that have been reported among older adolescents. PMID- 27665279 TI - Racial/Ethnic Disproportionality in Psychiatric Diagnoses and Treatment in a Sample of Serious Juvenile Offenders. AB - Psychiatric disorder prevalence has been shown demonstrably higher among justice involved adolescents than youth in the general population. Yet, among arrested juveniles, little is known regarding racial/ethnic differences in disorder prevalence, the role of trauma exposure in the diagnosis of behavioral disorders, or subsequent psychiatric treatment provided to adolescents with such diagnoses. The current study examines racial/ethnic disparity in psychiatric diagnoses and treatment of behavioral disorders associated with delinquency, controlling for traumatic experiences, behavioral indicators, and prior offending among serious juvenile offenders. Logistic regression is employed to explore the racial/ethnic disproportionality in behavioral disorder diagnoses and psychiatric treatment provision among 8763 males (57.7 % Black, 11.8 % Hispanic) and 1,347 females (53.7 % Black, 7.6 % Hispanic) admitted to long-term juvenile justice residential placements in Florida. The results indicate Black males are 40 % more likely, and Black females 54 % more likely to be diagnosed with conduct disorder than Whites, even upon considerations of trauma, behavioral indicators, and criminal offending. Black and Hispanic males are approximately 40 % less likely to be diagnosed with ADHD than White males, with no racial/ethnic differences for females. Importantly, Black males are 32 % less likely to receive psychiatric treatment than White males, with no differences between White and Hispanic males, or any female subgroups. Traumatic exposures increased the odds of oppositional defiant disorder and ADHD, but not conduct disorder for males, though adverse childhood experiences were unrelated to behavioral disorder diagnoses among females. PMID- 27665280 TI - Truncated EphA2 likely potentiates cell adhesion via integrins as well as infiltration and/or lodgment of a monocyte/macrophage cell line in the red pulp and marginal zone of the mouse spleen, where ephrin-A1 is prominently expressed in the vasculature. AB - We previously established a J774.1 monocyte/macrophage subline expressing a truncated EphA2 construct lacking the kinase domain. We demonstrated that following ephrin-A1 stimulation, endogenous EphA2 promotes cell adhesion through interaction with integrins and integrin ligands such as ICAM1 and that truncated EphA2 potentiates the adhesion and becomes associated with the integrin/integrin ligand complex. Based on these findings, we hypothesized that the EphA/ephrin-A system, particularly EphA2/ephrin-A1, regulates transendothelial migration/tissue infiltration of monocytes/macrophages, because ephrin-A1 is widely recognized to be upregulated in inflammatory vasculatures. To evaluate whether this hypothesis is applicable in the spleen, we screened for EphA2/ephrin-A1 expression and reexamined the cellular properties of the J774.1 subline. We found that ephrin-A1 was expressed in the vasculature of the marginal zone and the red pulp and that its expression was upregulated in response to phagocyte depletion; further, CD115, F4/80, and CXCR4 were expressed in J774.1 cells, which serve as a usable substitute for monocytes/macrophages. Moreover, following ephrin-A1 stimulation, truncated EphA2 did not detectably interfere with the phosphorylation of endogenous EphA2, and it potentiated cell adhesion possibly through modulation of integrin avidity. Accordingly, by intravenously injecting mice with equal numbers of J774.1 and the subline cells labeled with distinct fluorochromes, we determined that truncated EphA2 markedly potentiated preferential cell infiltration into the red pulp and the marginal zone. Thus, modulation of EphA2 signaling might contribute to effective transplantation of tissue-specific resident macrophages and/or monocytes. PMID- 27665281 TI - Targeting the gastrointestinal tract with viral vectors: state of the art and possible applications in research and therapy. AB - While there is a large body of preclinical data on the use of viral vectors in gene transfer, relatively little is known about viral gene transfer in the gastrointestinal tract. Viral vector technology is especially underused in the field of neurogastroenterology when compared to brain research. This review provides an overview of the studies employing viral vectors-in particular retroviruses, adenoviruses and adeno-associated viruses-to transduce different cell types in the intestine. Early work mainly focused on mucosal transduction, but had limited success due to the harsh luminal conditions in the gastrointestinal tract and the high turnover rate of enterocytes. More recently, several studies have successfully employed viral gene transfer to target the enteric nervous system and its progenitors. Although several hurdles still need to be overcome, in particular on how to augment transduction efficiency and specific cell targeting, viral vector technology holds strong potential not only as a valid research tool in fundamental gastroenterological research but also as a therapeutic agent in translational (bio)medical research. PMID- 27665282 TI - Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt-Jakob Disease in Slovak Patients: over 10-Year Period Review. AB - Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Abeta 1-42 levels neither between both CJD forms nor between CJD patients and control group. PMID- 27665283 TI - Pterostilbene Attenuates Early Brain Injury Following Subarachnoid Hemorrhage via Inhibition of the NLRP3 Inflammasome and Nox2-Related Oxidative Stress. AB - Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice. We also studied possible underlying mechanisms. After PTE treatment, the neurological score and brain water content of the mice were assessed. Oxidative stress and neuronal injury were also evaluated. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity was assessed using western blot analysis. Our results indicated that PTE treatment reduces the SAH grade, neurological score, and brain water content following SAH. PTE treatment also reduced NLRP3 inflammasome activation. PTE alleviated the oxidative stress following SAH as evidenced by the dihydroethidium staining, superoxide dismutase activity, malondialdehyde content, 3-nitrotyrosie and 8 hydroxy-2-deoxyguanosine levels, and gp91phox and 4-hydroxynonenal expression levels. Additionally, PTE treatment reduced neuronal apoptosis. In conclusion, our study suggests that PTE attenuates EBI following SAH possibly via the inhibition of NLRP3 inflammasome and Nox2-related oxidative stress. PMID- 27665285 TI - In reply: Rethinking general anesthesia for cesarean section. PMID- 27665286 TI - Erratum to: A Mechanism to Explain Ototoxicity in Neonates Exposed to Bumetanide: Lessons to Help Improve Future Product Development in Neonates. PMID- 27665287 TI - Palivizumab Exposure and the Risk of Autoimmune Disease: A Cross-National Cohort Study. AB - BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS: This was a population-based cohort study including data from 769,523 Danish children born between 1 January 1999 and 31 December 2010 and data from 581,742 Swedish children born between 1 July 2005 and 31 December 2010. RESULTS: Of the 1,351,265 children included, 1192 (0.09 %) were exposed to palivizumab. Nine cases of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80-2.95). CONCLUSION: The risk of autoimmune disease was not increased after palivizumab exposure. Given the small number of incident cases of autoimmune disease observed, this finding should be interpreted with caution. PMID- 27665284 TI - Abiotic stress miRNomes in the Triticeae. AB - The continued growth in world population necessitates increases in both the quantity and quality of agricultural production. Triticeae members, particularly wheat and barley, make an important contribution to world food reserves by providing rich sources of carbohydrate and protein. These crops are grown over diverse production environments that are characterized by a range of environmental or abiotic stresses. Abiotic stresses such as drought, heat, salinity, or nutrient deficiencies and toxicities cause large yield losses resulting in economic and environmental damage. The negative effects of abiotic stresses have increased at an alarming rate in recent years and are predicted to further deteriorate due to climate change, land degradation, and declining water supply. New technologies have provided an important tool with great potential for improving crop tolerance to the abiotic stresses: microRNAs (miRNAs). miRNAs are small regulators of gene expression that act on many different molecular and biochemical processes such as development, environmental adaptation, and stress tolerance. miRNAs can act at both the transcriptional and post-transcriptional levels, although post-transcriptional regulation is the most common in plants where miRNAs can inhibit the translation of their mRNA targets via complementary binding and cleavage. To date, expression of several miRNA families such as miR156, miR159, and miR398 has been detected as responsive to environmental conditions to regulate stress-associated molecular mechanisms individually and/or together with their various miRNA partners. Manipulation of these miRNAs and their targets may pave the way to improve crop performance under several abiotic stresses. Here, we summarize the current status of our knowledge on abiotic stress-associated miRNAs in members of the Triticeae tribe, specifically in wheat and barley, and the miRNA-based regulatory mechanisms triggered by stress conditions. Exploration of further miRNA families together with their functions under stress will improve our knowledge and provide opportunities to enhance plant performance to help us meet global food demand. PMID- 27665288 TI - Physical activity in patients with axial spondyloarthritis: a cross-sectional study of 203 patients. AB - Physical activity is recommended in axial spondyloarthritis (axSpA) but may be insufficiently performed. The objective of this study was to assess physical activity in axial spondyloarthritis and to explore its explanatory factors. This was a cross-sectional study of patients with definite axSpA. The level of physical activity (International Physical Activity Questionnaire-Long form, IPAQ L), type of aerobic exercise and the Exercise Benefits and Barriers Score were collected. Multivariate logistic regression analyses were performed to explain levels of exercise at least as recommended by the World Health Organization. In all, 203 patients were included: mean age 46.0 +/- 11.6 years, 108 (53.2 %) males, mean Bath Ankylosing Spondylitis Activity Index (0-100) 37.8 +/- 19.9; 137 (68.8 %) were treated with TNF-inhibitors. In all, 111 patients (54.7 %) were exercising at least as recommended; 96 (47.2 %) were in the 'high physical activity' category. Aerobic exercise >30 min was performed at least once a week by 61 (30.0 %) patients; the most frequent activities were energetic walking (31.0 %) and swimming (21.2 %). Main perceived benefits of exercising were improving physical fitness and functioning of the cardiovascular system, and the main barrier was physical exertion. Patients with paid employment had lower levels of physical activity whereas other demographic variables, disease activity/severity or TNF-inhibitor treatment were not predictive. One half of these patients performed enough physical activity according to the recommendations, similarly to the French population. Levels of physical activity did not appear to be explained by disease-related variables. Physical activity should be encouraged in axSpA. PMID- 27665289 TI - Medication adherence in patients with rheumatoid arthritis: why do patients not take what we prescribe? AB - Rheumatoid arthritis (RA) is an autoimmune inflammatory disease which results in extensive articular and extra-articular morbidity and increased mortality from cardiovascular disease. Despite an increasing range of non-biological and biological disease-modifying agents, poor patient adherence with medication is a significant barrier to effective control of the inflammation associated with RA. This review seeks to identify factors that affect patient adherence with medication, examine the effectiveness of interventions to address this issue and offer practical suggestions to improve medication adherence. The impact of health literacy on medication adherence and the novel role of musculoskeletal ultrasound as an educational intervention will also be discussed. PMID- 27665290 TI - Distinct Immunoregulatory Mechanisms in Mesenchymal Stem Cells: Role of the Cytokine Environment. AB - Mesenchymal stem cells (MSCs) represent a population of cells which have the ability to regulate reactivity of T and B lymphocytes by multiple mechanisms. The immunoregulatory activities of MSCs are strictly influenced by the cytokine environment. Here we show that two functionally distinct cytokines, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), significantly potentiate the ability of MSCs to inhibit IL-10 production by activated regulatory B cells (Bregs). However, MSCs in the presence of IL-4 or IFN-gamma inhibit the IL-10 production by different mechanisms. Preincubation of MSCs with IFN-gamma led to the suppression, but pretreatment with IL-4 of neither MSCs nor B cells resulted in the suppression of IL-10 production. The search for candidate regulatory molecules expressed in cytokine-treated MSCs revealed different patterns of the gene expression. Pretreatment of MSCs with IFN-gamma, but not with IL-4, induced expression of indoleamine-2,3-dioxygenase, cyclooxygenase-2 and programmed cell death-ligand 1. To identify the molecule(s) responsible for the suppression of IL 10 production, we used specific inhibitors of the putative regulatory molecules. We found that indomethacine, an inhibitor of cyclooxygenase-2 (Cox-2) activity, completely abrogated the inhibition of IL-10 production in cultures containing MSCs and IFN-gamma, but had no effect on the suppression in cell cultures containing MSCs and IL-4. The results show that MSCs can inhibit the response of B cells to one stimulus by different mechanisms in dependence on the cytokine environment and thus support the idea of the complexity of immunoregulatory action of MSCs. PMID- 27665292 TI - A simple method for developing an infectious cDNA clone of Japanese encephalitis virus. AB - Flavivirus cDNA clones frequently demonstrate genetic instability in transformed bacteria, which hampers the construction and manipulation of cDNAs for infectious flaviviruses. In this study, we developed a stable, full-length cDNA clone, pJEHEN, of a GI JEV strain HEN0701 using a medium-copy-number pBR322 vector and propagating cDNA clones at room temperature. The virus vJEHEN recovered from the infectious clone was indistinguishable from the parent virus HEN0701 with respect to plaque morphology, growth kinetics, and virulence characteristics. A T-to-A silent mutation of nucleotide 24 of the NS2a gene was introduced into the infectious cDNA clone to eliminate frameshifting. The rescued mutant virus vJETA did not express NS1' in infected cells and showed reduced growth and neurovirulence in mice. This convenient method for the construction and manipulation of infectious JEV cDNA clones may be of use in further studies to improve our understanding of the molecular mechanisms responsible for JEV replication and pathogenesis. PMID- 27665291 TI - Hyaluronic Acid (HA) Scaffolds and Multipotent Stromal Cells (MSCs) in Regenerative Medicine. AB - Traditional methods for tissue regeneration commonly used synthetic scaffolds to regenerate human tissues. However, they had several limitations, such as foreign body reactions and short time duration. In order to overcome these problems, scaffolds made of natural polymers are preferred. One of the most suitable and widely used materials to fabricate these scaffolds is hyaluronic acid. Hyaluronic acid is the primary component of the extracellular matrix of the human connective tissue. It is an ideal material for scaffolds used in tissue regeneration, thanks to its properties of biocompatibility, ease of chemical functionalization and degradability. In the last few years, especially from 2010, scientists have seen that the cell-based engineering of these natural scaffolds allows obtaining even better results in terms of tissue regeneration and the research started to grow in this direction. Multipotent stromal cells, also known as mesenchymal stem cells, plastic-adherent cells isolated from bone marrow and other mesenchymal tissues, with self-renew and multi-potency properties are ideal candidates for this aim. Normally, they are pre-seeded onto these scaffolds before their implantation in vivo. This review discusses the use of hyaluronic acid-based scaffolds together with multipotent stromal cells, as a very promising tool in regenerative medicine. PMID- 27665293 TI - An RCT into the effects of neurofeedback on neurocognitive functioning compared to stimulant medication and physical activity in children with ADHD. AB - Neurofeedback (NFB) is a potential alternative treatment for children with ADHD that aims to optimize brain activity. Whereas most studies into NFB have investigated behavioral effects, less attention has been paid to the effects on neurocognitive functioning. The present randomized controlled trial (RCT) compared neurocognitive effects of NFB to (1) optimally titrated methylphenidate (MPH) and (2) a semi-active control intervention, physical activity (PA), to control for non-specific effects. Using a multicentre three-way parallel group RCT design, children with ADHD, aged 7-13, were randomly allocated to NFB (n = 39), MPH (n = 36) or PA (n = 37) over a period of 10-12 weeks. NFB comprised theta/beta training at CZ. The PA intervention was matched in frequency and duration to NFB. MPH was titrated using a double-blind placebo controlled procedure to determine the optimal dose. Neurocognitive functioning was assessed using parameters derived from the auditory oddball-, stop-signal- and visual spatial working memory task. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses showed improved attention for MPH compared to NFB and PA, as reflected by decreased response speed during the oddball task [eta p2 = 0.21, p < 0.001], as well as improved inhibition, impulsivity and attention, as reflected by faster stop signal reaction times, lower commission and omission error rates during the stop-signal task (range eta p2 = 0.09-0.18, p values <0.008). Working memory improved over time, irrespective of received treatment (eta p2 = 0.17, p < 0.001). Overall, stimulant medication showed superior effects over NFB to improve neurocognitive functioning. Hence, the findings do not support theta/beta training applied as a stand-alone treatment in children with ADHD. PMID- 27665295 TI - Poly- and perfluoroalkylated substances (PFASs) in water, sediment and fish muscle tissue from Lake Tana, Ethiopia and implications for human exposure. AB - Lake Tana is Ethiopia's largest lake and there are plans to increase the harvest of fish from the lake. The objective of this study was to assess the levels of poly- and perfluoroalkyl substances (PFASs) in different compartments of the lake (water, sediment, and fish muscle tissue), and its implications for human exposure. The results showed higher PFAS concentrations in piscivorous fish species (Labeobarbus megastoma and Labeobarbus gorguari) than non-piscivorous species (Labeobarbus intermedius, Oreochromis niloticus and Clarias gariepinus) and also spatial distribution similarities. The ?PFAS concentrations ranged from 0.073 to 5.6 ng L-1 (on average, 2.9 ng L-1) in surface water, 0.22-0.55 ng g-1 dry weight (dw) (on average, 0.30 ng g-1 dw) in surface sediment, and non detected to 5.8 ng g-1 wet weight (ww) (on average, 1.2 ng g-1 ww) in all fish species. The relative risk (RR) indicates that the consumption of fish contaminated with perfluorooctane sulfonate (PFOS) will likely not cause any harmful effects for the Ethiopian fish eating population. However, mixture toxicity of the sum of PFASs, individual fish consumption patterns and increasing fish consumption are important factors to consider in future risk assessments. PMID- 27665296 TI - Analytical techniques for steroid estrogens in water samples - A review. AB - In recent years, environmental concerns over ultra-trace levels of steroid estrogens concentrations in water samples have increased because of their adverse effects on human and animal life. Special attention to the analytical techniques used to quantify steroid estrogens in water samples is therefore increasingly important. The objective of this review was to present an overview of both instrumental and non-instrumental analytical techniques available for the determination of steroid estrogens in water samples, evidencing their respective potential advantages and limitations using the Need, Approach, Benefit, and Competition (NABC) approach. The analytical techniques highlighted in this review were instrumental and non-instrumental analytical techniques namely gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS), enzyme-linked immuno sorbent assay (ELISA), radio immuno assay (RIA), yeast estrogen screen (YES) assay, and human breast cancer cell line proliferation (E-screen) assay. The complexity of water samples and their low estrogenic concentrations necessitates the use of highly sensitive instrumental analytical techniques (GC-MS and LC-MS) and non-instrumental analytical techniques (ELISA, RIA, YES assay and E-screen assay) to quantify steroid estrogens. Both instrumental and non-instrumental analytical techniques have their own advantages and limitations. However, the non-instrumental ELISA analytical techniques, thanks to its lower detection limit and simplicity, its rapidity and cost-effectiveness, currently appears to be the most reliable for determining steroid estrogens in water samples. PMID- 27665298 TI - Observation of ultrasonic guided wave propagation behaviours in pre-stressed multi-wire structures. AB - Ultrasonic guided wave (UGW) is a promising technique for nondestructive testing of pre-stressed multi-wire structures, such as steel strand and wire rope. The understanding of the propagation behaviours of UGW in these structures is a priority to applications. In the present study, first the properties of the UGW missing frequency band in the pre-stressed seven-wire steel strand is experimentally examined. The high correlation between the observed results and the previously published findings proves the feasibility of the magnetostrictive sensor (MsS) based testing method. The evolution of missing frequency band of UGW in slightly tensioned steel strand is discussed. Two calibration equations representing the relationship between the missing band parameters and the tensile force are given to derive a new tensile force measurement method, which is capable of measuring an incremental of stress of approximately 3MPa. Second, the effects of tensile force on the UGW propagation behaviours in three types of complicated steel wire ropes are alternatively investigated based on the short time Fourier transform (STFT) results of the received direct transmission wave (DTW) signals. The observed inherent missing frequency band of the longitudinal mode UGW in the pre-stressed steel wire rope and its shifting to a higher frequency range as the increases of the applied tensile force are reported for the first time. The influence of applied tensile force on the amplitude of the DTW signal and the unique UGW energy jump behaviour observed in a wire rope of 16.0mm, 6*Fi(29)+IWRC are also investigated, despite the fact that they cannot yet be explained. PMID- 27665297 TI - Guided wave scattering by geometrical change or damage: Application to characterization of fatigue crack and machined notch. AB - Validation of guided-wave based systems for Non-Destructive Evaluation (NDE) and Structural Health Monitoring (SHM) under realistic conditions or environment requires complex setups. For this purpose, numerical or theoretical approaches are useful to save time and cost associated with experiential tests. However, the interaction with realistic geometrical (rivets, thickness changes, stiffeners, extrusions) or damage features (fatigue cracks, fillet cracks, delaminations, disbonds) must be accurately captured in order to be representative. In this paper, an experimental methodology is presented for estimating the far-field scattering of geometrical or damage features. The principle is based on the use of a Hankel transform of the measured 3D velocity field in order to evaluate with precision and repeatability the scattered pattern using a spatially averaged method. Application to scattering of a hole with simulated machined and real fatigue cracks is proposed. It is observed that the simulated machined crack generally used as a reference standard can only model accurately the transmission behaviour while the scattering patterns are only similar when the wavelength is about the size of the crack, limiting the practical use of machined cracks for experimental validation of SHM or NDE systems. PMID- 27665294 TI - Disinfection of human musculoskeletal allografts in tissue banking: a systematic review. AB - Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanseTM Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method. PMID- 27665299 TI - Primary and Secondary Chemoprevention of Malignant Melanoma. AB - The incidence of malignant melanoma (MM) continues to rise in the United States. While sun protection and full body skin examinations remain the mainstay of preventative care, chemoprevention of the deadly disease has become an increasingly popular field of study. In this focused review, we discuss current findings and analyze the risks and benefits of various agents investigated for the primary and secondary chemoprevention of MM. Such agents include topical retinoids, vitamins, and supplements, Polypodium leucotomas extracts, non steroidal anti-inflammatory agents (NSAIDs), statins, sunscreens, and field therapy with topical imiquimod for primary and secondary chemoprevention. We further identify a need for expanded high quality human research on the topic. PMID- 27665300 TI - Adalimumab: A Review in Hidradenitis Suppurativa. AB - Subcutaneous adalimumab (Humira(r)) is a tumour necrosis factor-alpha blocker that is the only approved agent for the treatment of moderate to severe hidradenitis suppurativa (HS) in several countries worldwide. This article reviews the clinical efficacy and safety of subcutaneous adalimumab in patients with moderate to severe HS. In clinical trials (PIONEER I and II), a greater proportion of adalimumab than placebo recipients reached HS clinical response (HiSCR) at week 12. The main secondary endpoints, such as the proportion of patients with an abscess and inflammatory nodule count of <=2 at week 12, were significantly greater with adalimumab than with placebo in PIONEER II, but not in PIONEER I. In addition, adalimumab showed the potential to reduce the high health related quality of life burden of HS and increase patient satisfaction. HiSCR rates were generally maintained in the longer term, and the safety profile of adalimumab in patients with moderate to severe HS was consistent with the known safety profile of the drug for other indications, with no new emerging safety signals. Adalimumab is an effective and generally well tolerated treatment for patients with moderate to severe HS, and is the first agent approved for this difficult-to-treat disease. PMID- 27665302 TI - Access to Diabetes Care for Populations Experiencing Homelessness: an Integrated Review. AB - Populations experiencing homelessness with diabetes may encounter barriers to accessing comprehensive diabetes care to manage the condition, yet it is unclear to what extent this population is able to access care. We reviewed the literature to identify and describe the barriers and facilitators to accessing diabetes care and managing diabetes for homeless populations using the Equity of Access to Medical Care Framework. An integrated review of the literature was conducted and yielded 10 articles that met inclusion criteria. Integrated reviews search, summarize, and critique the state of the research evidence. Findings were organized using the dimensions of a comprehensive conceptual framework, the Equity of Access to Medical Care Framework, to identify barriers and facilitators to accessing care and managing diabetes. Barriers included competing priorities, limited access to healthy food, and inadequate healthcare resources. Facilitators to care included integrated delivery systems that provided both social and health related services, and increased patient knowledge. Recommendations are provided for healthcare providers and public health practitioners to optimize diabetes outcomes for this population. PMID- 27665303 TI - Mobile clinics in Haiti, part 1: Preparing for service-learning. AB - Mobile clinics have been used successfully to provide healthcare services to people in hard to reach areas around the world, but their use is sometimes controversial. There are advantages to using mobile clinics among rural underserved populations, and providing access to those who are vulnerable will improve health and decrease morbidity and mortality. However, some teams use inappropriate approaches to international service. For over 15 years, Azusa Pacific University School of Nursing has sponsored mobile clinics to rural northern Haiti with the aim to provide culturally sensitive healthcare in collaboration with Haitian leaders. Experience and exploring the literature have informed the APU-SoN approach on best practices for planning and preparing study abroad, service-learning trips that provide healthcare services. The authors hope that this description of the preparation and planning needed for appropriate and culturally sensitive service-learning experiences abroad will benefit others who seek to provide healthcare study abroad opportunities around the world. PMID- 27665301 TI - Does Zinc Really "Metal" with Diabetes? The Epidemiologic Evidence. AB - Zinc (Zn) is important in a number of processes related to insulin secretion and insulin activity in peripheral tissues, making this element an interesting potential co-adjuvant in the treatment of patients with type 2 diabetes (T2D). This issue has been matter of interest in recent years. The available evidence is analyzed in this review. Information from epidemiologic studies evaluating the relationship between Zn and T2D is inconsistent. Furthermore, few studies examined the association between Zn status and insulin action and/or glucose homeostasis. In terms of usefulness of Zn as a preventive agent for T2D development, information is insufficient to reach firm conclusions. Results from Zn supplementation trials found some positive effects only in those with initial sub normal Zn status in a significant proportion of individuals. In conclusion, the effect of Zn on patients with type 2 diabetes is still an open question, and better study designs are needed to clarify the real impact and characteristics of the Zn-diabetes interaction. PMID- 27665304 TI - Dignity and respect in midwifery education in the UK: A survey of Lead Midwives of Education. AB - In the UK respect, dignity and compassion are the underpinning values which must determine service user care in the National Health Service (NHS). In midwifery education it is unclear how students are being taught these values. We created a study that aimed to explore how learning about dignity and respect is facilitated and assessed within pre-registration midwifery curricula. An online survey was devised and distributed to all Lead Midwives for Education in the UK. The findings are presented under the three main themes of understanding the meaning of dignity and respect, teaching and assessment and experiences. The study concludes that, though there are some good areas of education practice there is inconsistency in how Nursing and Midwifery Council (NMC) guidelines are transferred into curricula. This leads to students receiving differing emphasis of education on the values of dignity and respect. PMID- 27665305 TI - Predelivery uterine arteries embolization in patients with placental implant anomalies: a cost-effective procedure. AB - Postpartum hemorrhages occur in 5 % of all deliveries. Open surgery and endovascular embolization techniques are the options commonly applied to face this life-threatening scenario. A cost analysis has been performed to compare the standard embolization endovascular approach, performed postpartum in emergency settlement, with a novel proposed preventive embolization approach, and performed in election in selected high-risk patients before the delivery. Two groups have been compared: 46 patients (non-preventive group) and 67 patients (preventive group). The computation of the detailed costs derived from the real costs supported by the hospital, based on the regional tariff in the period considered. The total expense for the 46 patients of the non-preventive group was 640.551,84? (13.925,04?/patient); all of them received transfusions and 43.4 % underwent to hysterectomy; the total expense for the 67 patients of the preventive group was 509.720,59? (7.607,77?/ patient); 36 % required transfusions and 26 % underwent to hysterectomy. Overall, in the preventive group, there is a mean saving of 45 %, it else 6.317?/patient. In this sample, predelivery uterine artery embolization has proved to be a cost-effective procedure, reducing the length of the hospital stay and the number of transfers to the intensive care unit, in pregnants with placental implant anomalies. PMID- 27665306 TI - Avoidance behavior of Eisenia fetida in oxytetracycline- and heavy metal contaminated soils. AB - To determine the behavior of oxytetracycline (OTC) and heavy metals in soil, this study assessed the pollutant-induced avoidance behavior of earthworms (E. fetida) exposed to zinc (Zn2+), lead (Pb2+), and OTC in soil. The results showed a clear avoidance response within 48h of exposure to the highest concentrations of pollutants. Moreover, E. fetida was shown to be more sensitive to Zn2+ than to Pb2+ and OTC. Compared with OTC alone, the net response of earthworms increased in the OTC-Zn2+ and OTC-Pb2+ combined treatments, indicating a synergistic effect. Moreover, the net response (NR) of the earthworms was higher for OTC-Zn2+ than it was for OTC-Pb2+, possibly reflecting the differences in essential characteristics of Zn and Pb. PMID- 27665308 TI - The impact of sleep loss on the facilitation of seizures: A prospective case crossover study. AB - PURPOSE: The relationship between sleep and seizures is intricate. The aim of this study was to assess whether sleep loss is an independent seizure precipitant in a clinical setting. METHODS: In this prospective, observational cross-over study, 179 consecutive hospital admissions for epileptic seizures were included. A semi-structured interview regarding several seizure precipitants was performed. The sleep pattern prior to the seizure, as well as alcohol, caffeine and drug use, were recorded. The interview was repeated by telephone covering the same weekday at a time when there had been no recent seizure. The Hospital Anxiety and Depression Scale (HADS) and a visual analogue scale for perceived stress were applied at admission. Student's t-test, Fisher exact test and ANOVA were used for statistical analyses. RESULTS: Complete data for analysis were retrieved in 144 patients. The sleep-time during the 24h prior to the seizure was lower (7.3h) compared to follow-up (8.3h; p<0.0005). Caffeine consumption and use of relevant non antiepileptic drugs (AED) were not different. HADS and stress scores at admission did not correlate with sleep-time difference. In ANOVA, controlled for alcohol consumption and AED use, the sleep-time difference remained significant (p=0.008). The interaction with alcohol intake was high, but the sleep-time difference remained highly significant also for the non- and low-consumption (<=2 units per day) subgroup (n=121, 7.50h vs 8.42h, p=0.001). CONCLUSION: Epileptic seizures are often precipitated by a combination of various clinical factors, but sleep loss stands out as an independent seizure trigger. PMID- 27665309 TI - Echovirus 1 internalization negatively regulates epidermal growth factor receptor downregulation. AB - We have demonstrated previously that the human picornavirus Echovirus 1 (EV1) triggers an infectious internalization pathway that follows closely, but seems to stay separate, from the epidermal growth factor receptor (EGFR) pathway triggered by epidermal growth factor (EGF). Here, we confirmed by using live and confocal microscopy that EGFR and EV1 vesicles are following intimately each other but are distinct entities with different degradation kinetics. We show here that despite being sorted to different pathways and located in distinct endosomes, EV1 inhibits EGFR downregulation. Simultaneous treatment with EV1 and EGF led to an accumulation of EGFR in cytoplasmic endosomes, which was evident already 15 min p.i. and more pronounced after 2 hr p.i. EV1 treatment led to reduced downregulation, which was proven by increased total cellular amount of EGFR. Confocal microscopy studies revealed that EGFR accumulated in large endosomes, presumably macropinosomes, which were not positive for markers of the early, recycling, or late endosomes/lysosomes. Interestingly, EV1 did not have a similar blocking effect on bulk endosomal trafficking or transferrin recycling along the clathrin pathway suggesting that EV1 did not have a general effect on cellular trafficking pathways. Importantly, EGF treatment increased EV1 infection and increased cell viability during infection. Simultaneous EV1 and EGF treatment seemed to moderately enhance phosphorylation of protein kinase C alpha. Furthermore, similar phenotype of EGFR trafficking could be produced by phorbol 12-myristate 13-acetate treatment, further suggesting that activated protein kinase C alpha could be contributing to EGFR phenotype. These results altogether demonstrate that EV1 specifically affects EGFR trafficking, leading to EGFR downregulation, which is beneficial to EV1 infection. PMID- 27665307 TI - Peripheral nerve injury induces adult brain neurogenesis and remodelling. AB - Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities. We demonstrate that these anatomical changes, partially reversible in the long term, result from adult neurogenesis. Neurogenic markers Mash1, Ngn2, doublecortin and Notch3 are widely expressed in the rodent cerebellum and pons, both under normal and injured conditions. CCI-induced hindbrain structural plasticity is absent in Notch3 knockout mice, a strain with impaired neuronal differentiation, demonstrating its dependence on adult neurogenesis. Grey matter and white matter structural changes in human brain, as a result of pain, injury or learned behaviours have been previously detected using non-invasive neuroimaging techniques. Because neurogenesis-mediated structural plasticity is thought to be restricted to the hippocampus and the subventricular zone, such anatomical rearrangements in other parts of the brain have been thought to result from neuronal plasticity or glial hypertrophy. Our findings suggest the presence of extensive neurogenesis-based structural plasticity in the adult mammalian brain, which may maintain a memory of basal sensory levels, and act as an adaptive mechanism to changes in sensory inputs. PMID- 27665310 TI - Percutaneous biliary approach as a successful rescue procedure after failed endoscopic therapy for drainage in advanced hilar tumors. AB - BACKGROUND AND AIM: Palliative endoscopic or percutaneous biliary drainage is used for unresectable advanced hilar cancer (HC). The best option for drainage in Bismuth type III or IV HC has not been established. The aims of this study are to identify factors predictive of endoscopic stenting failure and evaluate the effectiveness of rescue percutaneous stenting in patients with advanced HC. METHODS: Data from 110 patients with inoperable advanced HC were retrospectively reviewed. All received bilateral self-expandable metallic stents. Patients were divided into three groups: I, successful initial endoscopic stenting; II, unsuccessful initial endoscopic stenting, followed by percutaneous stenting; and III, initial percutaneous stenting. We analyzed clinical results and radiologic tumor characteristics. RESULTS: Baseline characteristics and clinical outcomes of all groups were similar, except the hospital stay was longer in group III than group I. Technical success rate was higher in groups II and III (100%) than in group I (72.4%). The functional success rate, stent patency time, patient survival time, and complication rate were similar between groups. Endoscopic stenting failed because of guide-wire passage failure (n = 12) or stent passage failure (n = 7). The only factor significantly associated with endoscopic failure was a smaller left intrahepatic duct-common bile duct angle. CONCLUSIONS: As clinical outcomes were generally similar between approaches, percutaneous stenting is recommended for patients with Bismuth type III or IV advanced HC. Acute left intrahepatic duct-common bile duct angulation predicts endoscopic stenting failure. If endoscopic stenting fails, immediate conversion to the percutaneous approach is a necessary and effective rescue method. PMID- 27665311 TI - Healthcare worker and family caregiver hand hygiene in Bangladeshi healthcare facilities: results from the Bangladesh National Hygiene Baseline Survey. AB - BACKGROUND: Healthcare facility hand hygiene impacts patient care, healthcare worker safety, and infection control, but low-income countries have few data to guide interventions. AIM: To conduct a nationally representative survey of hand hygiene infrastructure and behaviour in Bangladeshi healthcare facilities to establish baseline data to aid policy. METHODS: The 2013 Bangladesh National Hygiene Baseline Survey examined water, sanitation, and hand hygiene across households, schools, restaurants and food vendors, traditional birth attendants, and healthcare facilities. We used probability proportional to size sampling to select 100 rural and urban population clusters, and then surveyed hand hygiene infrastructure in 875 inpatient healthcare facilities, observing behaviour in 100 facilities. FINDINGS: More than 96% of facilities had 'improved' water sources, but environmental contamination occurred frequently around water sources. Soap was available at 78-92% of handwashing locations for doctors and nurses, but just 4-30% for patients and family. Only 2% of 4676 hand hygiene opportunities resulted in recommended actions: using alcohol sanitizer or washing both hands with soap, then drying by air or clean cloth. Healthcare workers performed recommended hand hygiene in 9% of 919 opportunities: more after patient contact (26%) than before (11%). Family caregivers frequently washed hands with only water (48% of 2751 opportunities), but with little soap (3%). CONCLUSION: Healthcare workers had more access to hand hygiene materials and performed better hand hygiene than family, but still had low adherence. Increasing hand hygiene materials and behaviour could improve infection control in Bangladeshi healthcare facilities. PMID- 27665312 TI - Corrigendum to 'Automated surveillance system for hospital-acquired urinary tract infections in Denmark' [Journal of Hospital Infection 93 (2016) 290-296]. PMID- 27665314 TI - Role of subcellular calcium redistribution in regulating apoptosis and autophagy in cadmium-exposed primary rat proximal tubular cells. AB - Ca2+ signaling plays a vital role in regulating apoptosis and autophagy. We previously proved that cytosolic Ca2+ overload is involved in cadmium (Cd) induced apoptosis in rat proximal tubular (rPT) cells, but the source of elevated cytosolic Ca2+ concentration ([Ca2+]c) and the effect of potential subcellular Ca2+ redistribution on apoptosis and autophagy remain to be elucidated. Firstly, data showed that Cd-induced elevation of [Ca2+]c was primarily generated intracellularly. Moreover, elevations of [Ca2+]c and mitochondrial Ca2+ concentration ([Ca2+]mit) with depletion of endoplasmic reticulum (ER) Ca2+ levels ([Ca2+]ER) were revealed in Cd-treated rPT cells, but this subcellular Ca2+ redistribution was significantly suppressed by 2-Aminoethoxydiphenyl borate (2-APB). Elevated inositol 1,4,5-trisphosphate (IP3) levels with up-regulated IP3 receptor (IP3R) protein levels were shown in Cd-exposed cells, confirming that IP3R-mediated ER Ca2+ release results in the elevation of [Ca2+]c. Up-regulated sequestosome 1 (p62) protein levels and autophagic flux assay demonstrated that Cd impaired autophagic degradation, while N-acetylcysteine (NAC) markedly attenuated Cd-induced p62 and microtubule-associated protein 1 light chain 3-II (LC3-II) accumulation, implying that the inhibition of autophagic flux was due to oxidative stress. Furthermore, pharmacological modulation of [Ca2+]c with 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and 2-APB alleviated Cd-mediated apoptosis, inhibition of autophagic degradation and subsequent cytotoxicity, while thapsigargin (TG) had the opposite regulatory effect on them. In summary, cytosolic calcium overload originated from IP3R mediated ER Ca2+ release has a negative impact on Cd nephrotoxicity through its promotion of apoptosis and inhibition of autophagic flux. PMID- 27665315 TI - Effects of metal ions and cosolutes on G-quadruplex topology. AB - Topologies of G-quadruplexes depend on oligonucleotide sequences and on environmental factors, and the diversity of G-quadruplex topologies complicates investigation of functions of these nucleic acid structures. To investigate how metal ions and cosolutes regulate topologies of G-quadruplexes, we stabilized the antiparallel conformation by insertion of 2'-deoxyxanthosine and 8-oxo-2' deoxyguanosine into selected positions of an oligonucleotide. Thermodynamic analyses of the oligonucleotide revealed that Na+ stabilized the antiparallel G quadruplex, whereas K+ destabilized this topology. This result suggests that metal ions selectively stabilize G-quadruplex topologies with cavities between G quartet planes of certain sizes. In the presence of KCl in 20wt% poly(ethylene glycol) with average molecular weight of 200, the antiparallel basket-type G quadruplex conformation was not stabilized compared with the dilute condition. In the presence of NaCl, the cosolute did stabilize the G-quadruplex with respect to the dilute condition. The presented data show that metal ions and cosolutes regulate topologies of G-quadruplexes through mechanisms that depend on sizes of metal ion cavities and hydration states. PMID- 27665313 TI - Unplanned 30-day hospital readmission as a quality measure in gynecologic oncology. AB - OBJECTIVES: Thirty-day readmission is used as a quality measure for patient care and Medicare-based hospital reimbursement. The primary study objective was to describe the 30-day readmission rate to an academic gynecologic oncology service. Secondary objectives were to identify risk factors and costs related to readmission. METHODS: This was a retrospective, concurrent cohort study of all surgical admissions to an academic, high volume gynecologic oncology service during a two-year period (2013-2014). Data were collected on patient demographics, medical comorbidities, psychosocial risk factors, and results from a hospital discharge screening survey. Mixed logistic regression was used to identify factors associated with 30-day readmission and costs of readmission were assessed. RESULTS: During the two-year study period, 1605 women underwent an index surgical admission. Among this population, a total of 177 readmissions (11.0%) in 135 unique patients occurred. In a surgical subpopulation with >1 night stay, a readmission rate of 20.9% was observed. The mean interval to readmission was 11.8days (SD 10.7) and mean length of readmission stay was 5.1days (SD 5.0). Factors associated with readmission included radical surgery for ovarian cancer (OR 2.87) or cervical cancer (OR 4.33), creation of an ostomy (OR 11.44), a Charlson score of >=5 (OR 2.15), a language barrier (OR 3.36), a median household income in the lowest quartile (OR 6.49), and a positive discharge screen (OR 2.85). The mean cost per readmission was $25,416 (SD $26,736), with the highest costs associated with gastrointestinal complications at $32,432 (SD $32,148). The total readmission-related costs during the study period were $4,523,959. CONCLUSIONS: Readmissions to a high volume gynecologic oncology service were costly and related to radical surgery for ovarian and cervical cancer as well as to medical, socioeconomic and psychosocial patient variables. These data may inform interventional studies aimed at decreasing unplanned readmissions in gynecologic oncology surgical populations. PMID- 27665316 TI - Chemical properties and biotoxicity of several chromium picolinate derivatives. AB - As a man-made additive, chromium picolinate Cr(pic)3 has become a popular dietary supplement worldwide. In this paper Cr(pic)3 and its new derivatives Cr(6-CH3 pic)3 (1), [Cr(6-NH2-pic)2(H2O)2]NO3 (2) and Cr(3-NH2-pic)3 (3) were synthesized, and complexes 1 and 2 were characterized by X-ray crystal structure (where pic=2 carboxypyridine). The relationship between the chemical properties and biotoxicity of these complexes was fully discussed: (1) The dynamics stability of chromium picolinate complexes mainly depends on the CrN bonds length. (2) There is a positive correlation between the dynamics stability, electrochemical potentials and generation of reactive oxygen species through Fenton-like reaction. (3) However, no biological toxicity was observed through MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and sub-chronic oral toxicity study for these chromium picolinate compounds. Together, our findings establish a framework for understanding the structure-property-toxicity relationships of the chromium picolinate complexes. PMID- 27665317 TI - Copper (II) and zinc (II) complexes with flavanone derivatives: Identification of potential cholinesterase inhibitors by on-flow assays. AB - Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEIs with inhibitory potency (IC50) and inhibitory constant (Ki) ranging from 0.02 to 4.5MUM. Copper complexes with flavanone bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC50 and Ki values of 0.012+/-0.002 and 0.07+/-0.01MUM for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC50=206+/-30.0 and Ki=126+/-18.0MUM). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC50 and Ki values of 8.0+/ 1.4 and 2.0+/-0.1MUM, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC50 and Ki values and the type of mechanism for the best inhibitors. PMID- 27665318 TI - Synthesis and biological evaluation of PEGylated CuO nanoparticles. AB - There is a growing field of research into the physicochemical properties of metal oxide nanoparticles (NPs) and their potential use against tumor formation, development and progression. Coated NPs with biocompatible surfactants can be incorporated into the natural metabolic pathway of the body and specifically favor delivery to the targeted cancerous cells versus normal cells. Polyethylene glycol (PEG) is an FDA approved, biocompatible synthetic polymer and PEGylated NPs are regarded as "stealth" nanoparticles, which are not recognized by the immune system. Herein, PEGylated cupric oxide nanoparticles (CuO NPs) with either PEG 1000 or PEG 8000 were hydrothermally prepared upon properly adjusting the reaction conditions. Depending on the reaction time CuO NPs in the range of core sizes 11-20nm were formed, while hydrodynamic sizes substantially varied (330 1120nm) with improved colloidal stability in PBS. The anticancer activity of the NPs was evaluated on human cervical carcinoma HeLa cells by using human immortalized embryonic kidney 293 FT cells as a control. Viability assays (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) revealed that CuO NPs could selectively reduce viability of tumor cells (IC50 values 11.91 25.78MUg/mL). Reactive oxygen species (ROS) production, cell membrane damage and apoptotic DNA laddering were also evident by nitroblue tetrazolium (NBT) reduction, lactate dehydrogenase (LDH) release assays and DNA electrophoresis, respectively. CuO NPs strongly inhibited lipoxygenase (LOX) enzymatic activity with IC50 values 4-5.9MUg/mL, highlighting in that manner their anti-inflammatory activity. PMID- 27665319 TI - [An original "double-arched" radial forearm flap for soft palate reconstruction. Case report]. AB - INTRODUCTION: Reconstruction of the soft palate after oncologic resection remains a surgical challenge. Speech and swallowing problems are the consequences of velopharyngeal incompetence following soft palate resection. Free tissue transfer like radial forearm flaps can be used in larger defects for complex reconstruction. The conformation of the flap in order to be closer to the shape of the soft palate improves the functional outcome. In the same way, we describe an original "double-arched" flap design. METHODS: A double arch of the exact length of the soft palate tumor resection is designed. After suturing, the flap spontaneously formed a double arch of the exact dimensions of the resected piece. RESULTS: The patient achieved good functional recovery without any surgical complications. CONCLUSION: The original "double-arched" forearm flap design allows a tailored reconstruction with exactly the same shape and dimensions, preserving the functional requirements of speech and deglutition. PMID- 27665321 TI - Prostate Cancer Focal Therapy: Just Because You Can Does Not Mean You Should. PMID- 27665320 TI - [The gluteus maximus inferior split-muscle flap for the cover of ischiatic pressure ulcers: Study of 61 cases]. AB - AIM OF THE STUDY: The coverage of ischiatic pressure ulcers is characterized by a significant recurrence rate (8-64% depending on the series). It therefore seems necessary to introduce the concept of saving in the use of muscle flaps available to avoid being in a situation of therapeutic impasse. The gluteus maximus inferior split-muscle flap allows a tailored coverage to the ischiatic pressure ulcers grade IV with skin defect less than 8cm after surgical debridement. It is associated with an advancement-rotation skin flap removed above the sub-gluteal fold. PATIENTS AND METHODS: The surgical treatment is performed in a single-stage (care+coverage), undercovered by probabilistic antibiotic per- and postoperative then secondarily adapted. After excision of the cavity, a gluteus maximus inferior split-muscle flap was realized. The inferior gluteal artery ensures the muscular flap vascularization. Afterwards, patients follow a rehabilitation program in a specialized center. RESULTS: Sixty-one flaps were performed in 55 patients between September 2000 and January 2015. Fifty-nine (97%) were conducted in first-line and 2 (3%) for covering recurrent pressure ulcers. After a mean duration of 4 years and 8 months follow-up, 13 pressure ulcers (21.3%) relapsed. If reoperation, a simple remobilization of the muscle flap was achieved in 54% of cases, a myocutaneous flap of biceps femoris in 23% and surgical abstention in a patient with non-compliant perioperative care. CONCLUSIONS: The gluteus maximus inferior split-muscle flap, simple to implement, provides coverage of ischial pressure sores while sparing muscle flaps usually used for this indication. The recurrence rate associated with the gluteus maximus inferior split-muscle flap is comparable to biceps femoris and gluteus maximus muscle flaps (totally harvested). It does not sacrifice function gluteus maximus muscle and can be performed in the valid patient. This flap keeps the Superior split-muscle, mobilized in case of sacral pressure ulcer. The gluteus maximus inferior split muscle flap is the first intention flap indicated for the cover of cover of ischiatic pressure ulcers of less than 8cm in diameter. PMID- 27665322 TI - Sildenafil, pulmonary hypertension and bronchopulmonary dysplasia. AB - Pulmonary hypertension (PH) secondary to bronchopulmonary dysplasia (BPD) in infants remains a serious concern and continues to cause significant morbidity despite improvements in both quality of life and survival for patients. One of the potential agents that might help is sildenafil citrate, a phosphodiesterase-V inhibitor used a first line therapy for idiopathic PH. However, only limited evidence exists for its use as either monotherapy or part of a combination approach towards the management of PH in BPD. The evidence and current knowledge is presented for sildenafil alone and in combination with other disease modifying agents to treat PH in the presence of BPD. We have previously suggested that sildenafil appears to be safe and possibly effective in this condition. We present the evidence that if continued until PH resolution, there might be reduced mortality in this debilitating disease. PMID- 27665323 TI - Natural radioactivity assessment of surface sediments in the Yangtze Estuary. AB - The activities of the natural radionuclides (238U, 232Th, 226Ra and 40K) of the surface sediments in the Yangtze Estuary were determined and used to evaluate radiation hazards in the study area. The of activities of 238U, 232Th, 226Ra and 40K ranges from 14.1 to 62.3, 26.1 to 71.9, 13.7 to 52.3, and 392 to 898Bqkg-1, respectively, which were comparable to values of other regions in China. The activities of 232Th, 40K and 226Ra were clearly different from the global recommended values. The radium equivalent activity was less than the recommended limit of 370Bqkg-1; therefore, the sediment in this area can be safely used for reclamation. The external hazard index values were less than one. The average absorbed gamma dose rate and annual effective dose equivalent values were slightly greater than the world average value. 226Ra/238U and 232Th/238U ratios could potentially be applied for tracing sediment source. PMID- 27665325 TI - Assessment of pollutant mean concentrations in the Yangtze estuary based on MSN theory. AB - Reliable assessment of water quality is a critical issue for estuaries. Nutrient concentrations show significant spatial distinctions between areas under the influence of fresh-sea water interaction and anthropogenic effects. For this situation, given the limitations of general mean estimation approaches, a new method for surfaces with non-homogeneity (MSN) was applied to obtain optimized linear unbiased estimations of the mean nutrient concentrations in the study area in the Yangtze estuary from 2011 to 2013. Other mean estimation methods, including block Kriging (BK), simple random sampling (SS) and stratified sampling (ST) inference, were applied simultaneously for comparison. Their performance was evaluated by estimation error. The results show that MSN had the highest accuracy, while SS had the highest estimation error. ST and BK were intermediate in terms of their performance. Thus, MSN is an appropriate method that can be adopted to reduce the uncertainty of mean pollutant estimation in estuaries. PMID- 27665324 TI - Bioremediation of contaminated coastal sediment: Optimization of slow release biostimulant ball using response surface methodology (RSM) and stabilization of metals from contaminated sediment. AB - The aim of the present study is to optimize the slow release biostimulant ball (BSB) for bioremediation of contaminated coastal sediment using response surface methodology (RSM). Metals contamination and stabilization of metals in coastal sediments using BSB were investigated. The effects of BSB size (1-5cm), distance (1-10cm), and time (1-4months) on the stabilization of metals including Fe, Cd, Cu, and Pb were determined. The maximum stabilization percentages of Fe, Cd, Cu, and Pb, of 64.5%, 54.9%, 63.8%, and 47.6%, respectively, were observed at a 3cm ball size, 5.5cm distance, and a period of 4months; these values are the optimum conditions for effective treatment of contaminated coastal sediment. The determination coefficient of the R2 value suggests that >91.55%, 89.97%, 96.10%, and 86.40% of the variance is attributable to the variables of Fe, Cd, Cu, and Pb, respectively. PMID- 27665326 TI - Frequency of genetic polymorphism for adrenergic receptor beta and cytochrome p450 2D6 enzyme, and effects on tolerability of beta-blocker therapy in heart failure with reduced ejection fraction patients: The Beta GenTURK study. AB - OBJECTIVE: The present objective was to determine frequency of Arginine389Glycine (Arg389Gly) and Cytochrome p450 2D6*10 (Cyp2D6*10) polymorphism in cases of heart failure-reduced ejection fraction (HFREF), and to evaluate the influence of the polymorphisms in response to beta-blocker (BB) therapy. METHODS: A total of 206 HFREF patients and 90 healthy controls were prospectively enrolled. Genotypes for Arg389Gly and Cyp2D6*10 polymorphisms of the healthy controls and 162 of the 206 heart failure (HF) patients were measured, identified by polymerase-chain reaction- and restriction-fragment-length-polymorphism analysis. HFREF patients and healthy controls were compared regarding Arg389Gly polymorphism. The HFREF patients were separated into 2 subgroups based on achievement of maximal target dose (MTD) of BB. RESULTS: When comparing frequency of genotype distribution for Arg389Gly polymorphism in HFREF patients to the healthy controls, a statistically significant association was observed with CC genotype and Glisin-Glisin (GG) genotype (p<0.001, odds ratio [OR]=16, confidence interval [CI]: 3.8-67.9 and p<0.001, OR=0.3, CI: 0.2-0.6). Frequency of genotypes for Arg389Gly and Cyp2D6*10 polymorphism were similar in patients who could or could not achieve BB MTD (p=0.13 and p=0.60, respectively). CONCLUSION: The frequency of Arg389Gly polymorphism in patients with HFREF in the present Turkish population differed from that of the healthy controls. However, neither Arg389Gly polymorphism nor Cyp2D6*10 polymorphism was associated with dose tolerability of BB therapy. PMID- 27665327 TI - Right ventricular function in coronary slow flow: A two-dimensional speckle tracking echocardiographic study. AB - OBJECTIVE: Coronary slow-flow phenomenon (CSFP) is described as protracted passage of angiographic contrast agent to the distal portion of the epicardial coronary arteries in the absence of stenosis. Few studies have addressed the effects of this condition on right ventricular (RV) dysfunction. The present objective was to assess RV function in CSFP via 2-dimensional speckle-tracking echocardiography (2DSTE). METHODS: A total of 29 patients with CSFP and 29 participants with normal coronary flow were compared regarding RV systolic and diastolic functions. Participants were matched for age, sex, hypertension, and diabetes mellitus. RV systolic and diastolic functions were evaluated with pulsed wave tissue Doppler echocardiography and 2DSTE. RESULTS: There were no statistically significant differences between the CSFP group and the control group regarding tissue Doppler echocardiographic and 2DSTE-derived indices. CONCLUSION: CSFP was not associated with tissue Doppler echocardiographic and 2DSTE-derived indices of RV systolic and diastolic function. PMID- 27665328 TI - Diagonal earlobe crease associated with increased epicardial adipose tissue and carotid intima media thickness in subjects free of clinical cardiovascular disease. AB - OBJECTIVE: Atherosclerotic coronary artery disease is a leading cause of death, worldwide. Diagonal earlobe crease (DELC) has been suggested as a simple, noninvasive marker of cardiovascular disease. Although epicardial adipose tissue (EAT) thickness and carotid intima media thickness (CIMT) are closely related to atherosclerosis, the relation between EAT, CIMT, and DELC had yet to be studied. The present objective was to analyze this association. METHODS: Subjects were apparently healthy individuals referred to the cardiology outpatient clinic. A total of 65 subjects with DELC and 65 age- and sex-matched controls without DELC were enrolled. EAT thickness and CIMT were measured and analyzed. RESULTS: Epicardial adipose tissue thickness was significantly higher in the DELC group (0.57+/-0.12 vs. 0.35+/-0.05; p<0.0001). CIMT was also significantly higher in DELC group (0.85+/-0.16 vs. 0.60+/-0.15; p<0.0001). Correlation analysis showed that CIMT was significantly correlated with EAT thickness (r: 0.594; p<0.0001). Linear regression analysis showed that presence of DELC was independently associated with CIMT and EAT thickness. CONCLUSION: A significant and independent association between the presence of DELC and increased CIMT and EAT thickness was presently determined, for the first time, in subjects free of clinical cardiovascular disease. PMID- 27665329 TI - Relationship between functional capacity and socioeconomic status in a cohort of Turkish heart failure patients. AB - OBJECTIVE: New York Heart Association (NYHA) classification predicts prognosis for heart failure (HF) patients. Socioeconomic status (SES) has the potential to affect treatment strategy and disease course. The present objective was to investigate whether SES of Turkish HF patients affected NYHA classification. METHODS: Turkish research team-HF (TREAT-HF) is a questionnaire study with 52 questions, the purpose of which is to aid in the assessment of various qualities of HF patients. The 2013 TREAT-HF cohort included 503 patients from 11 centers in Turkey. Patients were divided into 2 groups according to NYHA functional classification: I-II, a better functional classification, or III-IV, a poorer functional classification. In addition, patients were analyzed according to gender. RESULTS: Evaluated were NYHA functional classifications of 459 (326 males and 133 females) patients with a mean age of 59.7+/-14.07 years and a mean ejection fraction (EF) of 31.7+/-9.22%. Total monthly family income level of >=1000 TL, younger age, higher EF, and male gender were independently associated with better NYHA functional classification. In addition to EF, regular weight control was found to be independently associated with better NYHA classification for females, while younger age and income of >=1000 TL were independently associated with better NYHA classification for males. CONCLUSION: The present results demonstrated that SES was associated with NYHA functional classification in a cohort of Turkish HF patients. PMID- 27665330 TI - Physical inactivity and low quality of life of Turkish women after hospitalization for coronary heart disease: Inferences from EUROASPIRE III. AB - OBJECTIVE: The present objective was to compare changes in lifestyle between (i) Turkish women and Turkish men, and (ii) Turkish women and European women, after hospitalization for coronary heart disease (CHD). Risk factor management, physical activity, mood, and quality of life (QOL) indices were compared. METHODS: A total of 2268 women (25.3% of 8966 patients, mean age: 65.8+/-9.0 years) were interviewed using the European Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III). In the Turkey cohort, 65 women (mean age: 63.3+/-9.9 years) and 273 men (mean age: 59.1+/-9.6 years) were interviewed, and underwent clinical and biochemical tests at a minimum of 6 months after hospital admission. Patients completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), the International Physical Activity Questionnaire (IPAQ), the Hospital Anxiety and Depression Scale (HADS), and questionnaires assessing QOL. RESULTS: After hospitalization for CHD, (i) Turkish women have lower participation in cardiac rehabilitation (CR) programs and lower physical activity indices than European women, (ii) Turkish women have lower physical activity indices than Turkish men, (iii) HADS anxiety scores and HADS depression scores were higher for Turkish women than for Turkish men, (iv) HADS anxiety scores and HADS depression scores were higher for Turkish women than for European women, (v) QOL indices were lower for Turkish women than for either European women or Turkish men. CONCLUSION: Turkish women engage in less physical activity, have lower QOL, and have higher rates of depression and anxiety after hospitalization for CHD than either of the other groups assessed. Every effort should be made to increase physical activity, and CR program adherence in general, particularly in female patients. PMID- 27665331 TI - Cardiac evaluation in children with hemangiomas. AB - OBJECTIVE: Hemangiomas are tumors most commonly encountered in pediatric patients, and are frequently treated with propranolol. However, there are currently no standard methods for evaluating cardiac function in patients prior to propranolol treatment. The present study was designed to aid in the evaluation of pretreatment cardiac and effects of propranolol on vital signs in pediatric hemangioma patients. METHODS: A pediatric oncology specialist and a pediatric cardiology specialist examined all patients prior to initiation of propranolol treatment. All patients were examined by the same 2 physicians. Cardiac evaluation included complete echocardiogram and electrocardiography. From September 2009 to January 2014, 146 patients aged 4 days to 10 years were screened. RESULTS: No patient had cardiac contraindication to propranolol. The effect of hemangioma on left ventricle size was examined, but left ventricle dilatation was found in only 3 patients. However, 68 patients had abnormal echocardiogram: 17 had patent foramen ovale, 4 had ventricular septal defect, 9 had atrial septal defect (associated with right heart enlargement), 8 had patent ductus arteriosus, 6 had physiologic pulmonary stenosis, and 1 had an aortic coarctation. No contraindications to propranolol or side effects were observed. However, cardiac anatomic defects were more common in this patient group than in the general population. CONCLUSION: Hemangiomas in infants or children, even in small or premature infants, can be treated with propranolol without significant cardiac side effects. In addition, large dermal hemangiomas were not found to affect ventricular size in pediatric patients. PMID- 27665332 TI - Hypertrophic cardiomyopathy with Jeune syndrome: The first reported case. AB - Jeune syndrome (Asphyxiating thoracic dysplasia) is a rare dystrophy of the skeleton, inherited as an autosomal recessive condition. Patients develop a narrowed thorax, rhizomelic dwarfism, and hepatic, renal, and pancreatic abnormalities. High rates of pulmonary hypoplasia and pulmonary hypertension have been reported. Some patients die in early stages of life due to respiratory failure. The case of a patient referred with a history of severe asphyxiating birth, who had been diagnosed with Jeune syndrome and later hypertrophic cardiomyopathy (HCM) upon echocardiographic examination is described in the present report. This rare disease is discussed with respect to the current literature, as the present is the first reported case to be accompanied by HCM. PMID- 27665333 TI - First trans-subclavian transcatheter aortic valve replacement using Lotus valve system. AB - Transcatheter aortic valve implantation (TAVI), most commonly performed via retrograde femoral artery access, is a promising alternative to surgical aortic valve replacement in elderly, high-risk patients with severe aortic stenosis (AS). Approximately one-third of these patients suffer from severe iliofemoral arteriopathy, ruling out transfemoral approach. The case of a 74-year-old man with severe AS and bilateral iliofemoral arteriopathy treated with left trans subclavian (TS) TAVI using the Lotus valve system is described in the present report. PMID- 27665334 TI - Eosinophilic myocarditis associated with eosinophilic pneumonia and eosinophilia following antibiotic and narcotic analgesic treatment. AB - Eosinophilic myocarditis (EM) is a rare form of myocarditis that usually presents with heart failure due to eosinophilic infiltration. EM is often a component of hypereosinophilic syndrome (HES). HES is a rare disorder characterized by persistent, marked eosinophilia combined with organ system dysfunction. A 38-year old man was admitted to emergency services with left inguinal pain and fever, and was hospitalized with diagnosis of nephrolithiasis and urinary tract infection. Intravenous antibiotic therapy of 3 grams meropenem per day and analgesic of 50 mg pethidine per day were administered. Typical angina pectoris and dyspnea developed approximately 24 hours after treatment. Rash on the chest, and diminished bilateral lung sounds and rales were observed. Nonspecific changes were present on electrocardiogram. Laboratory analysis showed progressively increasing levels of cardiac biomarkers and eosinophilia. Peripheral blood smear, bone marrow aspiration, and biopsy demonstrated eosinophilia. Chest x-ray revealed diffuse, bilateral interstitial and reticulonodular infiltrates. Transthoracic echocardiography showed thickened left ventricle. Coronary angiography revealed normal coronary arteries. EM was suspected, endomyocardial biopsy was performed, and pathologic specimen confirmed the diagnosis. Corticosteroid treatment was initiated, and within 1 day, angina pectoris and dyspnea had dramatically reduced, and cardiac biomarkers and eosinophil count had decreased. Normal chest x-ray was observed after 72 hours. The patient was discharged with steroid treatment. PMID- 27665335 TI - Reverse Takotsubo cardiomyopathy following intra-abdominal surgery. AB - Reverse Takotsubo cardiomyopathy (RTC) is a rare condition characterized by systolic dysfunction of the basal segments of the left ventricle in the absence of obstructive coronary artery disease. The case of a 50-year-old woman with RTC following intra-abdominal surgery is described in the present report. PMID- 27665336 TI - [Congenitally corrected transposition of the great arteries in patient with atrial septal defect and acute inferior segment myocardial infarction]. AB - Congenitally corrected transposition of the great arteries is a rare abnormality accounting for approximately 1% of clinically apparent congenital heart disease. Age at time of diagnosis and survival rate vary and depend on associated anomalies, including pulmonary stenosis, ventricular septal defect, atrial septal defect, atrioventricular block, and atrioventricular valve regurgitation. Reported cases of corrected transposition of the great arteries with single coronary ostium anomaly and atrial septal defect are very rare. Described in the present report is the case of a 55-year-old male who presented with acute inferior ST-segment elevation myocardial infarction and coincidental single coronary ostium arising from the right sinus of Valsalva, as observed on coronary angiography. Successful balloon angioplasty and stenting of the circumflex artery were performed. Echocardiography demonstrated the corrected transposition of the great arteries with negative contrast enhancement between the atrial chambers. The patient was discharged with medical therapy on the eighth postoperative day. To our knowledge, the present is the first report to describe corrected transposition of the great arteries, atrial septal defect, single coronary ostium, and acute myocardial infarction as comorbidities. PMID- 27665337 TI - [Balloon valvuloplasty for aortic stenosis using umbilical vein access in a newborn: First experience in Turkey]. AB - Balloon valvuloplasty is an effective therapy for severe congenital aortic valve stenosis, with mild aortic insufficiency and minimal intermediate-term restenosis. No consensus currently exists regarding optimal vascular approach for balloon dilatation in newborns with critical or severe aortic valve stenosis. Critical aortic valve stenosis in newborns must be treated promptly and effectively. Transcatheter therapy may offer marked advantages, as surgical therapy has been associated with significant rates of morbidity and mortality. Percutaneous balloon dilatation is usually performed as emergent therapy of valve stenosis, with various options for vascular approach. While umbilical artery and vein access is rarely used in the treatment of critical aortic valve stenosis and aortic coarctation, this approach is a safe, simple, and effective choice for balloon dilatation in newborns, even in those weighing under 2.5 kg. PMID- 27665338 TI - Depression following coronary artery bypass grafting surgery revisited. AB - Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. Depression is a frequent comorbidity in patients with ischemic heart disease that can affect the course of the disease and the process of recovery after CABG. Depression after CABG is more common in women and is an independent predictor of mortality in long-term. However, fewer than half of cardiologists ask about depression symptoms in their patients, and with screening measures not being routinely utilized, depression remains under-recognized in this patient population. Treatment of depression in patients with ischemic heart disease can be challenging, considering unwanted medication side effects and interactions. The present report is a review of risk factors, prognosis, prevention, and treatment of depression in patients following CABG. PMID- 27665340 TI - Case images: An extremely unusual pacemaker complication. PMID- 27665339 TI - Case images: Massive liver hematoma secondary to overdose of warfarin treatment. PMID- 27665341 TI - Case images: Cannon 'A' waves during complete atrioventricular block. PMID- 27665342 TI - Case images: Left atrial appendage ostial stenosis in a patient with rheumatic mitral valve disease. PMID- 27665343 TI - Case images: Isolated accessory mitral valve leaflet. PMID- 27665344 TI - A patient with ventricular fibrillation and inverted Takotsubo syndrome triggered by sinus surgery: plausible causes, and electrocardiographic features. PMID- 27665345 TI - Authors' reply. PMID- 27665346 TI - Cholesterol embolization syndrom. PMID- 27665347 TI - Authors' reply. PMID- 27665349 TI - Authors' reply. PMID- 27665348 TI - Ductus arteriosus aneursym causing hoarseness which is the best treatment option; surgery or endovascular? PMID- 27665351 TI - A physics based approach to the pulse wave velocity prediction in compliant arterial segments. AB - Pulse wave velocity (PWV) quantification commonly serves as a highly robust prognostic parameter being used in a preventative cardiovascular therapy. Being dependent on arterial elastance, it can serve as a marker of cardiovascular risk. Since it is influenced by a blood pressure (BP), the pertaining theory can lay the foundation in developing a technique for noninvasive blood pressure measurement. Previous studies have reported application of PWV, measured noninvasively, for both the estimation of arterial compliance and blood pressure, based on simplified physical or statistical models. A new theoretical model for pulse wave propagation in a compliant arterial segment is presented within the framework of pseudo-elastic deformation of biological tissue undergoing finite deformation. An essential ingredient is the dependence of results on nonlinear aspects of the model: convective fluid phenomena, hyperelastic constitutive relation, large deformation and a longitudinal pre-stress load. An exact analytical solution for PWV is presented as a function of pressure, flow and pseudo-elastic orthotropic parameters. Results from our model are compared with published in-vivo PWV measurements under diverse physiological conditions. Contributions of each of the nonlinearities are analyzed. It was found that the totally nonlinear model achieves the best match with the experimental data. To retrieve individual vascular information of a patient, the inverse problem of hemodynamics is presented, calculating local orthotropic hyperelastic properties of the arterial wall. The proposed technique can be used for non-invasive assessment of arterial elastance, and blood pressure using direct measurement of PWV, with account of hyperelastic orthotropic properties. PMID- 27665350 TI - Characterization of three dimensional volumetric strain distribution during passive tension of the human tibialis anterior using Cine Phase Contrast MRI. AB - Intramuscular pressure correlates strongly with muscle tension and is a promising tool for quantifying individual muscle force. However, clinical application is impeded by measurement variability that is not fully understood. Previous studies point to regional differences in IMP, specifically increasing pressure with muscle depth. Based on conservation of mass, intramuscular pressure and volumetric strain distributions may be inversely related. Therefore, we hypothesized volumetric strain would decrease with muscle depth. To test this we quantified 3D volumetric strain in the tibialis anterior of 12 healthy subjects using Cine Phase Contrast Magnetic Resonance Imaging. Cine Phase Contrast data were collected while a custom apparatus rotated the subjects' ankle continuously between neutral and plantarflexion. A T2-weighted image stack was used to define the resting tibials anterior position. Custom and commercial post-processing software were used to quantify the volumetric strain distribution. To characterize regional strain changes, the muscle was divided into superior inferior sections and either medial-lateral or anterior-posterior slices. Mean volumetric strain was compared across the sections and slices. As hypothesized, volumetric strain demonstrated regional differences with a decreasing trend from the anterior (superficial) to the posterior (deep) muscle regions. Statistical tests showed significant main effects and interactions of superior-inferior and anterior-posterior position as well as superior-inferior and medial-lateral position on regional strain. These data support our hypothesis and imply a potential relationship between regional volumetric strain and intramuscular pressure. This finding may advance our understanding of intramuscular pressure variability sources and lead to more reliable measurement solutions in the future. PMID- 27665352 TI - Diameter and thickness-related variations in mechanical properties of degraded arterial wall in the rat xenograft model. AB - The purpose of this study was to evaluate the diameter and thickness-related variations in mechanical properties of degraded arterial wall. To this end, ring tests were performed on 31 samples from the rat xenograft model of abdominal aortic aneurysm (AAA) and failure properties were determined. An inverse finite element method was then employed to identify the material parameters of a hyperelastic and incompressible strain energy function. Correlations with outer diameter and wall thickness of the rings were examined. Furthermore, we investigated the changes in mechanical properties between the grafts, which consist in guinea pig decellularized aortas, native murine aortas and degraded aortas (AAAs). Decellularized aortas presented a significantly lower ultimate strain associated with a higher stiffening rate compared to native aortas. AAAs exhibited a significantly lower ultimate stress than other groups and an extensible-but-stiff behavior. The proposed approach revealed correlations of ultimate stress and material parameters of aneurysmal aortas with outer diameter and thickness. In particular, the negative correlations of the material parameter accounting for the response of the non-collagenous matrix with diameter and thickness (r=-0.67 and r=-0.73, p<0.001) captured the gradual loss of elastin with dilatation observed in histology (r=-0.97, p<0.001). Moreover, it exposed the progressive weakening of the wall with enlargement and thickening (r=-0.64 and r=-0.69, p<0.001), suggesting that wall thickness and diameter may be indicators of rupture risk in the rat xenograft model. PMID- 27665353 TI - The role of healthcare provider attitudes in increasing willingness to accept seasonal influenza vaccine policy changes. AB - BACKGROUND: This research explored the role of attitudes in acceptance of organizational change initiatives. METHODS: A survey assessed factors associated with health care provider (HCP) likelihood to accept seasonal influenza vaccine policy changes. We evaluated the impact of knowledge and individual attitudes on this outcome measure. RESULTS: Knowledge of seasonal influenza vaccine and influenza recommendations was a significant predictor of HCP's attitudes toward vaccine at the individual (p<0.001), organizational (p<0.05), and legislative level (p<0.05). Mixed results were obtained when investigating the impact of knowledge on actual willingness to accept vaccine, suggesting that knowledge was only a significant predictor at the organizational (p<0.05) and legislative levels (p<0.05). Attitudes fully mediated the impact of knowledge at both the organizational and legislative levels. INTERPRETATION: Knowledge of seasonal influenza and vaccine recommendations is an important, but insufficient predictor of willingness to accept policy change. PMID- 27665355 TI - Infectious bronchitis virus poly-epitope-based vaccine protects chickens from acute infection. AB - Infectious bronchitis virus (IBV) causes major losses in the poultry industry. The safe and effective vaccine to control IBV spread is imperative. In the present study, we developed IBV S1 glycoprotein poly-epitope-based DNA vaccine pV S1B+S1T consisting of SH1208 and Holte strain BF2-restricted T cell epitopes and Australian T strain dominant B cell neutralization epitopes. Specific pathogen free chickens were vaccinated with pV-S1B+S1T and control plasmids twice to elicit strong humoral and cellular immune response, as indicated by viral neutralization titers and results of CD8+ T cell proliferation assays. A lethal dose of IBV SH1208 strain used for protection and challenge experiments at two weeks post-booster immunization following challenge protection and virus shedding reverse transcription quantitative PCR assay, indicated that pV-S1B+S1T protected against IBV and significantly reduced viral excretion. These results demonstrated that the IBV poly-epitope-based vaccine effectively prevents infection and represents a potential IBV vaccine. PMID- 27665354 TI - Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant. AB - Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4+ T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum-specific interferon gamma (IFNgamma) driven-Th1 responses become dampened and a state of immune exhaustion established. T cell exhaustion and other immunoregulatory processes, starting during asymptomatic disease, are likely to hinder vaccine-induced responses if vaccine is administered to infected, but asymptomatic and seronegative, individuals. In this study we evaluated how immune exhaustion, shown previously by our group to worsen in concert with VL progression, effected the capacity of vaccine candidate antigen/toll-like receptor (TLR) agonist combinations to promote protective CD4+ T cell responses during progressive VL. In conjunction with Th1 responses, we also evaluated concomitant stimulation of immune-balanced IL-10 regulatory cytokine production by these vaccine products in progressive VL canine T cells. Vaccine antigen L111f in combination with TLR agonists significantly recovered CD4+ T cell IFNgamma intracellular production in T cells from asymptomatic VL dogs. Vaccine antigen NS with TLR agonists significantly recovered CD4+ T cell production in both endemic control and VL dogs. Combinations of TLR agonists and vaccine antigens overcame L. infantum induced cellular exhaustion, allowing robust Th1 CD4+ T cell responses from symptomatic dogs that previously had dampened responses to antigen alone. Antigen-agonist adjuvants can be utilized to promote more robust vaccine responses from infected hosts in endemic areas where vaccination of asymptomatic, L. infantum-infected animals is likely. PMID- 27665356 TI - The effect of HER2 status on oncological outcomes of patients with invasive bladder cancer. AB - PURPOSE: The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with oncological outcomes. METHODS: This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes. RESULTS: HER2 was overexpressed in 36% of patients. HER2 overexpression was associated with features of tumor aggressiveness such as lymph node metastases (P = 0.002). At a median follow-up of 123 months (interquartile range: 79-180), 160 patients (45%) experienced disease recurrence, 263 patients (74%) died and 157 (44%) died of cancer. On multivariable analyses, HER2 overexpression was not significantly associated with any oncological outcomes. Adding HER2 status to a model for the prediction of survival outcomes did not change the accuracy of the model for any of the outcomes. Interestingly, HER2 status significantly affected late disease recurrence (P = 0.05 for conditional survival at 24 months). CONCLUSIONS: More than one third of RC patients overexpress HER2 in their tumors. HER2 overexpression was associated with features of biological and clinical aggressiveness. HER2 did not add prognostic significance to the standard established predictors of survival outcomes after RC. However, due to the high overexpression rate, it could represent a target for therapy in select advanced BCa tumors. PMID- 27665359 TI - Chemotherapy in frail elderly patients with metastatic castration-resistant prostate cancer? PMID- 27665357 TI - Prostate magnetic resonance imaging findings in patients treated for testosterone deficiency while on active surveillance for low-risk prostate cancer. AB - OBJECTIVE: To investigate the multiparametric prostate magnetic resonance imaging (mpMRI) findings in patients treated with testosterone replacement therapy (TRT) while on active surveillance for low-risk prostate cancer. METHODS: We retrospectively reviewed 12 patients who underwent mpMRI before and after TRT while on active surveillance. Changes in serum testosterone level, prostate specific antigen (PSA), prostate biopsy findings, prostate volume, and Prostate Imaging Reporting and Data System Version 2 (PI-RADSv2) score before and after TRT were summarized. RESULTS: After TRT, there was a significant increase in serum testosterone (516.5ng/dl vs. 203.0ng/dl), PSA (4.2ng/ml vs. 3.3ng/ml), and prostate volume (55.2cm3 vs. 39.4cm3). In total, 2 patients had biopsy progression during the study period. The PI-RADSv2 scores before and after TRT were unchanged in 10/12 patients; none of these demonstrated biopsy progression on post-TRT. The PI-RADSv2 scores increased after TRT in 2/12 patients; both showed Gleason score upgrade on follow-up biopsy. Of these 2 patients, 1 patient underwent radical treatment due to clinical progression. The area under the curve for detecting biopsy progression calculated from PI-RADSv2 score after TRT was 0.90, which was better than that calculated from post-TRT PSA level (0.48). CONCLUSIONS: After TRT, mpMRI findings remained stable in patients without biopsy progression, whereas PI-RADSv2 score increase was identified in patients with Gleason score upgrade on follow-up biopsy. PMID- 27665358 TI - KIFC1 induces resistance to docetaxel and is associated with survival of patients with prostate cancer. AB - OBJECTIVES: Prostate cancer (PCa) is a common malignancy worldwide. Docetaxel has been an important treatment option for patients with metastatic castration resistant prostate cancer (CRPC). However, nearly all patients with CRPC treated with docetaxel eventually become refractory. In the present study, we analyzed the expression and distribution of kinesin family member C1 (KIFC1) in human PCa by immunohistochemistry and examined the effect of inhibiting KIFC1 expression on docetaxel resistance. METHODS: Expression of KIFC1 was determined using immunohistochemistry. RNA interference was used to inhibit KIFC1 expression in PCa cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) assays. CONCLUSIONS: These results indicate that KIFC1 plays an important role in PCa progression. Immunohistochemical analysis of KIFC1 would facilitate identification of patients with poor prognoses after radical prostatectomy, as well as patients with poor therapeutic outcomes after docetaxel-based chemotherapy. PMID- 27665360 TI - Impending anterior myocardial infarction: de Winter syndrome. PMID- 27665361 TI - Difference in Transcranial Doppler Velocity and Patient Age between Proximal and Distal Middle Cerebral Artery Vasospasms after Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. METHODS: This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. RESULTS: Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. CONCLUSIONS: In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients. PMID- 27665363 TI - Caring for carers in community pharmacy. PMID- 27665362 TI - Upstaging and survival after robotic-assisted thoracoscopic lobectomy for non small cell lung cancer. AB - BACKGROUND: Mediastinal involvement in resected non-small-cell lung cancer mandates adjuvant therapy and affects survival. This study investigated lymph node dissection efficacy, lymph node metastasis detection, and survival after robotic-assisted lobectomy for non-small-cell lung cancer. METHODS: We retrospectively analyzed patients who underwent robotic-assisted lobectomy for non-small-cell lung cancer. Survival was assessed through chart reviews, Social Security Death Registry, and national obituary searches. Kaplan-Meier survival curves by clinical and pathologic stage were compared by log-rank and Cox regression analysis. RESULTS: In 249 patients (mean age, 67.8 +/- 0.6 years), mean individual mediastinal lymph nodes retrieved was 7.7 +/- 0.3 lymph nodes, with mean of 13.9 +/- 0.4 N1+ mediastinal lymph nodes. There were 159 (63.9%) clinical stage I versus 134 (53.8%) pathologic stage I patients, with 67 (26.9%) patients upstaged (20 cN0 to pN1; 17 cN0 to pN2; 4 cN1 to pN2) and 37 (14.9%) downstaged. One-year and 3-year survival rates, respectively, changed between clinical stage I (clinical stage I, 91% and 70%; clinical stage II, 80% and 64%; clinical stage III, 78% and 57%; clinical stage IV, 71% and 45%) and pathologic stage (pathologic stage I, 92% and 75%; clinical stage II, 83% and 73%; pathologic stage III, 75% and 44%; and pathologic stage IV, 67% and 0%). CONCLUSION: Mediastinal lymph node dissection during robotic-assisted lobectomy adequately assesses lymph node stations and detects occult lymph node metastasis. Stage-specific survival is affected by upstaging. PMID- 27665365 TI - Resuscitation following opioid overdose: More are needed. PMID- 27665364 TI - Pharmacist-led medication review in community settings: An overview of systematic reviews. AB - BACKGROUND: Pharmacist-led medication review is a collaborative service which aims to identify and resolve medication-related problems. OBJECTIVE: To critically evaluate published systematic reviews relevant to pharmacist-led medication reviews in community settings. METHODS: MEDLINE, EMBASE, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 1995 to December 2015. Systematic reviews of all study designs and outcomes were considered. Methodological quality was assessed using the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool. Systematic reviews of moderate or high quality (AMSTAR >= 4) were included in the data synthesis. Data extraction and quality assessment was performed independently by two investigators. RESULTS: Of the 35 relevant systematic reviews identified, 24 were of moderate and seven of high quality and were included in the data synthesis. The largest overall numbers of unique primary research studies with favorable outcomes were for diabetes control (78% of studies reporting the outcome), blood pressure control (74%), cholesterol (63%), medication adherence (56%) and medication management (47%). Significant reductions in medication and/or healthcare costs were reported in 35% of primary research studies. Meta-analysis was performed in 12 systematic reviews. Results from the meta-analyses suggested positive impacts on glycosylated hemoglobin, blood pressure, cholesterol, and number and appropriateness of medications. Conflicting findings were reported in relation to hospitalization. No meta-analyses reported reduced mortality. CONCLUSION: Moderate and high quality systematic reviews support the value of pharmacist-led medication review for a range of clinical outcomes. Further research including more rigorous cost analyses are required to determine the impact of pharmacist-led medication reviews on humanistic and economic outcomes. Future systematic reviews should consider the inclusion of both qualitative and quantitative studies to comprehensively evaluate medication review. PMID- 27665366 TI - Chemotherapy in hormone-sensitive metastatic prostate cancer: Evidences and uncertainties from the literature. AB - Data from the literature support with strong evidence the addition of docetaxel to androgen-deprivation therapy (ADT) for men with metastatic prostate cancer, and starting therapy for the first time. A meta-analysis of three randomized controlled trials showed a significant improvement of overall survival when ADT was combined with docetaxel when compared to ADT alone (HR=0.77; 95% CI: 0.68 0.87; p<0.0001). Consequently, combination therapy should be considered presently as the new standard of care, using 6 cycles of docetaxel, without prednisone. However, candidates for this upfront combination therapy in whom the balance between its side effects and benefits is favorable are still to be identified more precisely. Patients' stratification according to Gleason score, previous local treatment and age or performance status were shown to have a prognostic impact. The volume of metastases, as defined in the CHAARTED study for instance, could be an interesting predictive factor. However, data accumulated until now remain only hypothesis generating and further analysis and studies are needed to establish any potential discriminating factors. Several new efficient therapeutic options are now available in prostate cancer management and should be evaluated against a chemo-hormonal combination therapy. Other trials are warranted to establish the role of docetaxel in earlier stages of the disease, the combination with the new hormonal therapies as well as the best management options after docetaxel. PMID- 27665368 TI - Preparation of soluble isotopically labeled human growth hormone produced in Escherichia coli. AB - Isotopically labeled proteins have been used as internal standards for mass spectrometry (MS)-based absolute protein quantification. Although this approach can provide highly accurate analyses of proteins of interest within a complex mixture, one of the major limitations of this method is the difficulty in preparing uniformly labeled standards. Human growth hormone (hGH) is one of the most important hormones that circulate throughout the body, and its measurement is primarily of interest in the diagnosis and treatment of growth disorders. In order to provide a useful internal standard for MS-based hGH measurement, we describe an efficient strategy to produce a potentially valuable, stable isotope labeled hGH with high purity and yield. The strategy involves the following steps: solubilization of hGH under labeling conditions, detection of stable isotope incorporation, large-scale purification, analysis of the labeled protein, and assessment of the labeling efficiency. We show that the yield of soluble hGH under selective isotopic labeling conditions can be greatly increased by optimizing protein expression and extraction. Our efficient method for generating isotopically labeled hGH does not influence the structural integrity of hGH. Finally, we assessed the efficiency of stable isotope labeling at the intact protein level, and the result was further verified by amino acid analysis. These results clearly indicate that our labeling approach allows an almost complete incorporation of 13C615N4-arginine into the hGH expressed in E.coli without detectable isotope scrambling. PMID- 27665367 TI - The eyespot resistance genes Pch1 and Pch2 of wheat are not homoeoloci. AB - KEY MESSAGE: Phenotyping and mapping data reveal that chromosome intervals containing eyespot resistance genes Pch1 and Pch2 on 7D and 7A, respectively, do not overlap, and thus, these genes are not homoeloci. Eyespot is a stem-base fungal disease of cereals growing in temperate regions. Two main resistances are currently available for use in wheat. Pch1 is a potent single major gene transferred to wheat from Aegilops ventricosa and located on the distal end of chromosome 7D. Pch2, a moderate resistance deriving from Cappelle Desprez, is located at the end of 7AL. The relative positions of Pch1 and Pch2 on 7D and 7A, respectively, suggest that they are homoeoloci. A single seed decent recombinant F7 population was used to refine the position of Pch2 on 7A. New markers designed to 7D also allowed the position of Pch1 to be further defined. We exploited the syntenic relationship between Brachypodium distachyon and wheat to develop 7A and 7D specific KASP markers tagging inter-varietal and interspecific SNPs and allow the comparison of the relative positions of Pch1 and Pch2 on 7D and 7A. Together, phenotyping and mapping data reveal that the intervals containing Pch1 and Pch2 do not overlap, and thus, they cannot be considered homoeloci. Using this information, we analysed two durum wheat lines carrying Pch1 on 7A to determine whether the Ae.ventricosa introgression extended into the region associated with Pch2. This identified that the introgression is distal to Pch2 on 7A, providing further evidence that the genes are not homoeoloci. However, it is feasible to use this material to pyramid Pch1 and Pch2 on 7A in a tetraploid background and also to increase the copy number of Pch1 in combination with Pch2 in a hexaploid background. PMID- 27665370 TI - Estrogenic compound attenuates angiotensin II-induced vascular smooth muscle cell proliferation through interaction between LKB1 and estrogen receptor alpha. AB - The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit VSMC proliferation and explored the underlying mechanisms. Both the phosphorylation and expression of LKB1 were increased by NDGA. In addition, NDGA significantly attenuated angiotensin II (Ang II)-induced VSMC proliferation. To elucidate the estrogenic effects, we confirmed that NDGA increased estrogen receptor alpha (ERalpha) expression, similar to treatment with E2 and estriol (E3). Furthermore, tamoxifen and ERalpha siRNA obstructed the effects of NDGA including ERalpha expression, AMPK phosphorylation and both LKB1 phosphorylation and expression. VSMC proliferation was restored by tamoxifen and ERalpha siRNA. LKB1 siRNA also reversed the NDGA-mediated inhibition of VSMC proliferation. The estrogenic activity of NDGA induced LKB1 translocation from nucleus to cytosol, and tamoxifen obstructed LKB1 translocation. The absence of LKB1 completely abolished the increase of ERalpha expression induced by NDGA. Taken together, the beneficial effects of estrogenic compound (E2 and NDGA) on inhibition of VSMC proliferation are mediated by interaction between LKB1 and ERalpha, suggesting a potential mechanism for females having less cardiovascular disease. PMID- 27665371 TI - Evaluation of influenza vaccine-immunogenicity in cell-mediated immunity. AB - The immunological effect of influenza vaccines cannot be evaluated accurately using an antibody titer. Therefore, we used a new method that measures cell mediated immunity to investigate changes in the amount of interferon-gamma (IFN gamma) produced after vaccination in response to the vaccine antigen. The study was conducted during the 2014-2015 influenza season in 23 adults, using a vaccine that contained three types of antigen. The IFN-gamma level increased by at least 1.5 times in 65% (15/23) of cases in response to the H1N1 antigen, in 57% (13/23) of cases in response to the H3N2 antigen, and in 57% (13/23) of cases in response to the B antigen. During the study period, 4 subjects developed type A influenza. Our data showed that the IFN-gamma level did not increase by 1.5 times in these subjects. We propose that the efficacy of influenza vaccines may be evaluated by measuring changes in the level of IFN-gamma produced in response to influenza vaccine. PMID- 27665369 TI - Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing. AB - In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-beta1 expression and scarless repair, while low Fm levels correlated with increased TGF-beta1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM-TGF-beta1 nexus plays in fetal-type scarless skin repair. PMID- 27665372 TI - Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study). AB - OBJECTIVE: To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412). DESIGN: Quantitative and qualitative analysis of questionnaire responses. SETTING: International randomised trial (94 sites, 15 countries). POPULATION/SAMPLE: 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85mmHg) or 'less tight' (target diastolic blood pressure, 100mmHg) who completed questionnaires. METHODS: A questionnaire was administered at ~6-12 weeks postpartum regarding post discharge morbidity and views about trial participation. Questionnaires were administered by the site co-ordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p<0.001 for statistical significance. NVivo software was used for thematic analysis of women's views. MAIN OUTCOME MEASURES: Satisfaction, measured as willingness to have the same treatment in another pregnancy or recommend that treatment to a friend. RESULTS: Among the 533 women in 'tight' (N=265) vs. 'less tight' (N=268) control who provided comments for qualitative analysis, women in 'tight' (vs. 'less tight') control made fewer positive comments about the amount of medication taken (5 vs. 28 women, respectively) and intensity of BP monitoring (7 vs. 17, respectively). However, this did not translate into less willingness to either have the same treatment in another pregnancy (434, 95.8% vs. 423, 92.4%, respectively; p=0.14) or recommend that treatment to a friend (435, 96.0% and 428, 93.4%, respectively; p=0.17). Importantly, although satisfaction remained high among women with an adverse outcome, those in 'tight' control who suffered an adverse outcome (vs. those who did not) were not consistently less satisfied, whereas this was not the case among women in 'less tight' control among whom satisfaction was consistently lower for the CHIPS primary outcome (p<0.001), severe hypertension (p<=0.01), and pre-eclampsia (p<0.001). CONCLUSIONS: Women in 'tight' (vs. 'less tight') control were equally satisfied with their care, and more so in the face of adverse perinatal or maternal outcomes. PMID- 27665373 TI - Juvenile myoclonic epilepsy: Challenges on its 60th anniversary. AB - PURPOSE: Since its initial 1957 description, juvenile myoclonic epilepsy (JME) has been recognized as a common epileptic syndrome worldwide. METHODS: We reviewed a series of articles on JME to clarify challenges in clinical and pathophysiological findings, treatment and outcome. RESULTS: Typical JME characteristics include: 1) the age at seizure onset between 10 and 25 years; 2) the triad of myoclonia, generalized tonic-clonic seizures, and absences, of which only myoclonia is a mandatory criterion; 3) cognitive dysfunction that may have impact on interpersonal relationships and social outcome; 4) possibility of seizure control in up to 80% of individuals, in particular with the use of sodium valproate; 5) a tendency for lifelong seizures with an early morning preponderance; 6) after decades from the clinical onset, a possibility to be off medications for a third of the patients, and 7) several prognostic factors. CONCLUSION: After 60 years, several challenges remain in this complex epileptic syndrome. PMID- 27665374 TI - S100P is a potential molecular target of cadmium-induced inhibition of human placental trophoblast cell proliferation. AB - Cadmium, a common and highly toxic pollutant, has been known to accumulate high concentrations in placenta with deleterious effects on placental structure and function. Cadmium inhibits cell proliferation in placenta via targeting metal binding proteins. S100P, a Ca2+-binding protein, plays an important role in promoting cell proliferation and our previous study found its downregulation was linked to cadmium exposure in Guiyu, a famous e-waste recycling town in China. So, the present study was aimed to define whether cadmium inhibited cell proliferation through interfering with S100P. Using human trophoblast-derived HTR 8/SVneo cells as a model in vitro, we showed that cadmium exposure led to decreases in both cell proliferation and S100P expression. Knockdown of S100P in HTR-8/SVneo cells led to an obvious decrease of cell proliferation, and upregulation of S100P resulted in a significant increase of cell proliferation. Furthermore, after 24h of exposure to cadmium (20MUM), cells transfected with pcDNA3.1-S100P showed a 1.3-fold higher S100P protein level, 38% higher proliferation evaluated with MTT assay than cells with no transfection, indicating that S100P expression attenuated cadmium-induced inhibition of cell proliferation. Taken together, we demonstrate that cadmium inhibits S100P expression and cell proliferation in placenta, meanwhile, S100P expression affects cell proliferation. Thus, our study is the first to indicate that cadmium may induce inhibition of placental trophoblast cell proliferation through targeting S100P. PMID- 27665375 TI - E-learning: Training Attendings to objectively assess Pediatric Urology Residents' performance of open surgery. PMID- 27665376 TI - Psychiatric dimensions in mothers of children with primary nocturnal enuresis: A controlled study. AB - INTRODUCTION: The etiology of primary nocturnal enuresis (PNE) is not fully understood, but multifactorial factors have been associated with PNE. Parental factors, including attitudes to PNE, disciplinary behaviors, and psychiatric comorbidities in parents have been related to etiology of PNE, outcomes and the quality of life in children with enuresis. OBJECTIVE: We examined the psychopathology in mothers of children diagnosed with monosymptomatic PNE(MoPNE) compared with mothers of non-enuretic children (MoNEC) in terms of personality characteristics, early traumatic experiences, and psychiatric symptom evaluation. STUDY DESIGN: The study included 44 mothers of children diagnosed with PNE and 45 mothers of non-enuretic children who were randomly selected from the population applying to the pediatric outpatient clinic. Individuals were assessed through psychometric questionnaires, including the Eysenck Personality Questionnaire Revised Abbreviated (EPQR-A), the Symptom Checklist-90 (SCL-90-R), and the Childhood Trauma Questionnaire (CTQ), in addition to a sociodemographic form including 9 structured "yes/no" questions that evaluated intrafamilial relationships, as well as mothers' perceptions of enuresis and its treatment. RESULTS: The median age of enuretic children was 7 (6, 9.5) (25th, 75th) years in the study population. The rates of history of enuresis in childhood were 26.7% in the MoPNE group (n = 12) and 6.7% in the MoNEC group (n = 3; p = 0.011). There were significant differences between the groups for the subscales of somatization, anxiety, obsessive-compulsive behavior, depression, interpersonal sensitivity, psychoticism, hostility, phobic anxiety, additional items, and the general psychopathology index in the SCL-90-R scores (p < 0.05). Meanwhile, there was no significant difference for the subscale of paranoid ideation (p = 0.070). There were statistically significant results for the subscales of sexual abuse, physical neglect, and total score in CTQ scale, while the personality dimensions evaluated using the EPQR-A resulted in significant differences in the E and L subscales (p < 0.05) (Table). CONCLUSION: Our study showed that psychiatric symptomatology and childhood traumatic experiences were considerably higher in mothers of children with PNE. This study highlights the importance of evaluating PNE not only from a biological aspect, but also in terms of psychosocial factors, including assessment of the mother's mental status. PMID- 27665377 TI - Novel benzoquinoline derivatives via unpredicted condensation of ethyl propiolate and naphthylamines: Synthesis and topoisomerase inhibition activity. AB - An unpredicted condensation of naphthylamine with two molecules of ethyl propiolate yields directly carbethoxy benzoquinoline in high yield. Some benzoquinoline carboxamide derivatives with protonatable side chains were then synthesized and evaluated for antiproliferative activity on human tumor cell lines. The most active compound (7a) demonstrated to intercalate into DNA and to inhibit the relaxation activity mediated by topoisomerase II. PMID- 27665378 TI - The importance of cyclic structure for Labaditin on its antimicrobial activity against Staphylococcus aureus. AB - Antimicrobial resistance has reached alarming levels in many countries, thus leading to a search for new classes of antibiotics, such as antimicrobial peptides whose activity is exerted by interacting specifically with the microorganism membrane. In this study, we investigate the molecular-level mechanism of action for Labaditin (Lo), a 10-amino acid residue cyclic peptide from Jatropha multifida with known bactericidal activity against Streptococcus mutans. We show that Lo is also effective against Staphylococcus aureus (S. aureus) but this does not apply to its linear analogue (L1). Using polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS), we observed with that the secondary structure of Lo was preserved upon interacting with Langmuir monolayers from a phospholipid mixture mimicking S. aureus membrane, in contrast to L1. This structure preservation for the rigid, cyclic Lo is key for the self-assembly of peptide nanotubes that induce pore formation in large unilamellar vesicles (LUVs), according to permeability assays and dynamic light scattering measurements. In summary, the comparison between Labaditin (Lo) and its linear analogue L1 allowed us to infer that the bactericidal activity of Lo is more related to its interaction with the membrane. It does not require specific metabolic targets, which makes cyclic peptides promising for antibiotics without bacteria resistance. PMID- 27665379 TI - Tumor targeting strategies for chitosan-based nanoparticles. AB - Currently, targeted nanoparticles (NPs) are rapidly being developed to overcome various bottlenecks of antitumor agents, such as poor solubility in aqueous solution, poor pharmacokinetics, a lack of selectivity and undesirable side effects in healthy tissues. In recent years, chitosan, a cationic polysaccharide, has been widely explored for the targeted delivery of antitumor agents due to its unique physicochemical and biological properties, such as biocompatibility, biodegradability, mucoadhesive feature, absorption enhancement and active functional groups for chemical modifications. This article reviews the recent developments in various target-specific nanoparticles based on chitosan and its derivatives, including passive, active and stimuli-sensitive targeting strategies. In addition, the target mechanisms and the key efficacy factors are illuminated. PMID- 27665380 TI - Elaboration of a finite element model of pancreatic islet dielectric response to gap junction expression and insulin release. AB - Dielectric spectroscopy could potentially be a powerful tool to monitor isolated human pancreatic islets for applications in diabetes therapy and research. Isolated intact human islets provide the most relevant means to understand the cellular and molecular mechanisms associated with diabetes. The advantages of dielectric spectroscopy for continuous islet monitoring are that it is a non invasive, inexpensive and real-time technique. We have previously assessed the dielectric response of human islet samples during stimulation and differentiation. Because of the complex geometry of islets, analytical solutions are not sufficiently representative to provide a pertinent model of islet dielectric response. Here, we present a finite element dielectric model of a single intact islet that takes into account the tight packing of islet cells and intercellular junctions. The simulation yielded dielectric spectra characteristic of cell aggregates, similar to those produced with islets. In addition, the simulation showed that both exocytosis, such as what occurs during insulin secretion, and differential gap junction expression have significant effects on islet dielectric response. Since the progression of diabetes has some connections with dysfunctional islet gap junctions and insulin secretion, the ability to monitor these islet features with dielectric spectroscopy would benefit diabetes research. PMID- 27665381 TI - Amphiphilic azobenzene-neomycin conjugate self-assembles into nanostructures and transports plasmid DNA efficiently into the mammalian cells. AB - The present study demonstrates the use of self-assembled nanostructures of cationic amphiphilic azobenzene-neomycin (a small molecule) conjugate, Azo-Neo, as delivery vector for plasmid DNA. These nanostructures efficiently condensed nucleic acid and formed more compact nanoassemblies. DLS analysis showed size and zeta potential of the resulting Azo-Neo/pDNA nanoassemblies ~153.7nm and +7.26mV, respectively. The nanoassemblies were characterized by physicochemical techniques and evaluated for its toxicity and ability to deliver nucleic acid therapeutics. The flow cytometry results on MCF-7 and HEK293T cells revealed that Azo-Neo/pDNA nanoassemblies transfected ~31% and 23% cells, respectively, at a w/w ratio of 250, while the standard transfection reagent, bPEI/pDNA complex, could transfect only ~21% and 29% cells, respectively, at its best w:w ratio of 2.3. MTT and hemolysis assays showed the non-toxic nature of the projected nanoassemblies and nanostructures, respectively, at various concentrations. Further, Azo-Neo nanostructures showed efficient antibacterial activity against different strains, laboratory strain of Staphylococcus aureus (MTCC 740) as well as MRSA strains (Staphylococcus aureus ATCC 33591, ATCC 43300 and ATCC 700699). These results ensure the great potential of these nanostructures in gene delivery and antimicrobial applications. PMID- 27665383 TI - Blood Eosinophil Count and Outcomes in Severe Uncontrolled Asthma: A Prospective Study. AB - BACKGROUND: Severe uncontrolled asthma (SUA) is associated with increased asthma exacerbations. Whether high blood eosinophil counts are related to this burden is uncertain. OBJECTIVES: To determine the relationship of blood eosinophil counts to asthma exacerbations, utilization, and cost in patients with SUA. METHODS: Patients with persistent asthma (age >= 12 years) were identified administratively with SUA in phase I by evidencing (1) 2 or more asthma exacerbations; (2) 6 or more medium- or high-dose dispensed canisters of inhaled corticosteroid (ICS) as monotherapy or with long-acting beta2-agonist; and (3) 3 or more dispensed non-ICS controllers. Of the 541 patients with SUA invited to participate in the prospective phase II follow-up study, 261 (48.2%) had blood tests (index date) to determine eosinophil count and other atopic biomarkers. The relationship of blood eosinophil cutoff points to asthma exacerbations and direct costs 1 year after the index date were determined by multivariable regression. RESULTS: A blood eosinophil cutoff point of greater than or equal to 400 cells/mm3 compared with less than 400 cells/mm3, but not 150 cells/mm3 or 300 cells/mm3, was a risk factor in the outcome year in adjusted analyses for 2 or more asthma exacerbations (risk ratio, 1.55; 95% CI, 1.02-2.35; P =.04) and any asthma emergency department visit or hospitalization (risk ratio, 2.29; 95% CI, 1.16-4.55; P =.02), but not for rate of asthma exacerbations or incremental total direct asthma costs per patient ($202; 95% CI, -286 to 691). CONCLUSIONS: A high blood eosinophil count was an independent risk factor for 2 or more asthma exacerbations or any asthma emergency department visit or hospitalization, but not direct costs in patients with SUA, possibly constrained by limited power. PMID- 27665382 TI - Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features. AB - BACKGROUND: Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. OBJECTIVE: This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response. METHODS: Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups. RESULTS: Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration. CONCLUSIONS: Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects. PMID- 27665384 TI - Dust Mite-Induced Perennial Allergic Rhinitis in Pediatric Patients and Sublingual Immunotherapy. AB - Allergic rhinitis (AR) is a common illness in children and can impair their quality of life. Furthermore, many children remain symptomatic despite maximizing systemic antihistamine and topical therapies. It is at this clinical juncture that immunotherapy may be considered. The efficacy and safety associated with both subcutaneous (SCIT) and sublingual (SLIT) approaches are reviewed and positioned as treatment options for pediatric patients, with specific focus on current literature as it relates to SLIT in children, including those with perennial allergic rhinitis. Although there is more extensive experience with SLIT treatment in Europe, grass and ragweed tablet forms of SLIT are approved in the US. Approaches to the care of pediatric patients with allergic rhinitis are presented. PMID- 27665385 TI - Development and Initial Validation of a Questionnaire to Measure Health-Related Quality of Life of Adults with Common Variable Immune Deficiency: The CVID_QoL Questionnaire. AB - BACKGROUND: Generic health status quality of life (QoL) instruments have been used in patients with common variable immune deficiency (CVID). However, by their nature, these tools may over- or underestimate the impact of diseases on an individual's QoL. OBJECTIVE: The objective of this study was to develop and validate a questionnaire to measure specific-health-related QoL for adults with CVID (CVID_QoL). METHODS: The 32-item content of the CVID_QoL questionnaire was developed using focus groups and individual patient interviews. Validation studies included 118 adults with CVID who completed Short Form-36, Saint George Respiratory Questionnaire, General Health Questionnaire-12, and EuroQol-5D questionnaire in a single session. Principal component and factor analysis solutions identified 3 scores to be similar in number and content for each solution. Validation of 3 factor scores was performed by construct validity. Reproducibility, reliability, convergent validity, and discriminant validity were evaluated. Matrices consisting of correlations between the 32 items in the CVID_QOL were calculated. RESULTS: Factor analysis identified 3 dimensions: emotional functioning (EF), relational functioning (RF), and gastrointestinal and skin symptoms (GSS). The instrument had good internal consistency (Cronbach's alpha, min. 0.74 for GSS, max. 0.84 for RF, n = 118) and high reproducibility (intraclass correlation coefficient, min. 0.79 for RF, max 0.90 for EF, n = 27). EF and RF scores showed good convergent validity correlating with conceptually similar dimensions of other study scales. Acute and relapsing infections had a significant impact on EF and RF. CONCLUSIONS: This study provides evidence of the reliability and construct validity of the CVID_QoL to identify QoL issues in patients with CVID that may not be addressed by generic instruments. PMID- 27665386 TI - Emergency Department Management of Hereditary Angioedema Attacks: Patient Perspectives. AB - BACKGROUND: Emergency department (ED) management of hereditary angioedema (HAE) has been hindered by misdiagnosis and limited treatment options. Food and Drug Administration approval of 4 on-demand HAE therapies starting in 2009 and the publication of ED guidelines for angioedema management in 2014 should facilitate improvement of HAE management in the ED. OBJECTIVE: The objective of this study was to identify patient-reported areas for improvement in ED management of HAE attacks. METHODS: Patients with self-reported HAE with C1 inhibitor deficiency who attended the 2015 HAE Association Patient Summit were asked to complete an anonymous 30-question survey. Questions addressed patient characteristics and HAE management in the ED. RESULTS: Patients indicated that understanding of HAE in the ED needed improvement (99%, 104 of 105 patients). Recognition of HAE as a diagnosis (48%, 50 of 105 patients), appreciation of HAE as a serious disease (45%, 47 of 105 patients), and medication management (59%, 62 of 105 patients) were identified as areas needing improvement. Among 39 patients who required ED care within the last year, 6 did not receive any HAE-targeted therapy, and treatment with corticosteroids (n = 3), epinephrine (n = 2), and antihistamines (n = 7) was reported. Among 68 patients whose treatment plan was to receive home on-demand therapy, 26 required ED care because of an inability to receive on demand therapy at home as outlined in their treatment plan. Having a treatment plan was associated with a greater likelihood of receiving HAE therapy in the ED (99% vs 74%, P = .002). CONCLUSION: HAE management in the ED can be improved with a focus on recognition of HAE attacks and administration of effective HAE therapies. PMID- 27665387 TI - Home Environmental Interventions for the Prevention or Control of Allergic and Respiratory Diseases: What Really Works. AB - Home health care workers interventions have been implemented in western countries to improve health status of patients with respiratory diseases especially asthma and allergic illnesses. Twenty-six controlled studies dealing with prevention and control of these diseases through home environmental interventions were reviewed. After a comprehensive description of the characteristics of these studies, the effectiveness of each intervention was then evaluated in terms of participants' compliance with the intervention program, improvement of quality of the indoor environment, and finally improvement of health outcomes, in detailed tables. Limitations and biases of the studies are also discussed. Overall, this review aims at giving a toolbox for home health care workers to target the most appropriate measures to improve health status of the patient depending on his and/or her environment and disease. Only a case-by-case approach with achievable measures will warrant the efficacy of home interventions. This review will also provide to the research community a tool to better identify targets to focus in future evaluation studies of home health care workers action. PMID- 27665388 TI - Rapid response to omalizumab in 3 cases of delayed pressure urticaria. PMID- 27665389 TI - Topical nalfurafine exhibits anti-inflammatory and anti-pruritic effects in a murine model of AD. PMID- 27665390 TI - JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation. AB - BACKGROUND: Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis. OBJECTIVE: To clarify the action site of JAK inhibitors in skin inflammatory disorders. METHODS: We analyzed the mechanism of action of the JAK inhibitor JTE-052 using murine skin inflammation models, including contact hypersensitivity (CHS) and irritant contact dermatitis. Cells isolated from ear tissue or lymph node (LN) were analyzed by flow cytometry. The amounts of cytokines in the culture medium were measured by ELISA or bead array system. Proliferation of LN cells was evaluated by measurement of tritiated thymidine incorporation. RESULTS: Oral administration of JTE-052 during both sensitization and elicitation phase attenuated CHS, but did not affect croton oil-induced irritant contact dermatitis. JTE-052 potently inhibited T cell proliferation and activation by antigen presentation in vitro, and attenuated skin inflammation in a sensitized-lymphocyte transfer model without suppressing T cell migration. JTE 052 did not affect hapten-induced cutaneous dendritic cell migration into draining lymph nodes or their costimulatory molecule expressions. CONCLUSION: The JAK inhibitor JTE-052 exerts an inhibitory effect on antigen-specific T cell activation and subsequent inflammation in acquired skin immunity, such as CHS. PMID- 27665391 TI - The effects of kinesio taping on the color intensity of superficial skin hematomas: A pilot study. AB - OBJECTIVES: To analyze the effects of kinesio taping (KT) -applied with three different strains that induced or not the formation of skin creases (called convolutions)- on color intensity of post-surgical superficial hematomas. DESIGN: Single-blind paired study. SETTING: Rehabilitation clinic. PARTICIPANTS: A convenience sample of 13 inpatients with post-surgical superficial hematomas. INTERVENTIONS: The tape was applied for 24 consecutive hours. Three tails of KT were randomly applied with different degrees of strain: none (SN); light (SL); and full longitudinal stretch (SF). We expected to obtain correct formation of convolutions with SL, some convolutions with SN, and no convolutions with SF. MAIN OUTCOME MEASURES: The change in color intensity of hematomas, measured by means of polar coordinates CIE L*a*b* using a validated and standardized digital images system. RESULTS: Applying KT to hematomas did not significantly change the color intensity in the central area under the tape (p > 0.05). There was a significant treatment effect (p < 0.05) under the edges of the tape, independently of the formation of convolutions (p > 0.05). CONCLUSIONS: The changes observed along the edges of the tape could be related to the formation of a pressure gradient between the KT and the adjacent area, but were not dependent on the formation of skin convolutions. PMID- 27665392 TI - Kinesiology taping does not alter shoulder strength, shoulder proprioception, or scapular kinematics in healthy, physically active subjects and subjects with Subacromial Impingement Syndrome. AB - OBJECTIVE: To examine the effect of kinesiology tape (KT) on shoulder strength, proprioception, and scapular kinematics in healthy and Subacromial Impingement Syndrome (SAIS) subjects. DESIGN: Placebo-controlled quasi-experimental study. SETTING: Research laboratory. PARTICIPANTS: A total of 30 physically active subjects participated. Ten healthy subjects with no previous history of shoulder pathology received KT on the dominant shoulder. Twenty subjects with shoulder pain for a minimum of two weeks and presenting with clinical signs of impingement were allotted to receive KT (n = 10) or placebo taping (PT, n = 10) on the involved shoulder. MAIN OUTCOME MEASURES: All participants were tested pre- and post-application. Shoulder internal/external rotation (IR/ER) strength was assessed with isokinetic dynamometry (average peak torque/body weight). Shoulder IR/ER proprioception was assessed through threshold to detect passive motion (mean absolute error in degrees). Scapular position at 90 degrees and 120 degrees of shoulder abduction during arm raising/lowering were assessed using a 3D motion analysis system. RESULTS: No significant within group or between group differences were demonstrated for any measure. CONCLUSIONS: Taping does not appear to aid/impair shoulder strength, shoulder proprioception, or scapular kinematics. Future research should explore if the effects of KT are time dependent and similar in other pathologies. PMID- 27665393 TI - Robot-assisted laparoscopic liver resection: A review. AB - Surgery using a robotic platform is expanding rapidly today, with a notable surge since its authorization on the international medical market by the US Food and Drug Administration in 2000. The first hepatectomy by a robotic approach was reported in 2002, 10 years after the first laparoscopic hepatectomy. Yet, in hepatic surgery, series are scarce and the lack of relevant data in the literature is an obstacle to the development of robot-assisted laparoscopic hepatectomy (RALH). Based on a review of the literature, this update focuses on current indications, short-term and oncologic outcomes following RALH. PMID- 27665394 TI - Effect of functional electrical stimulation on the proprioception, motor function of the paretic upper limb, and patient quality of life: A case report. AB - : Functional electrical stimulation (FES) has shown to improve motor function of the affected side in stroke patients; however, the effects of FES on proprioception, the functional recovery of the paretic upper limb, and the patient quality of life (QoL) are not clear. The aim of the current case report was to determine whether FES can improve joint position sense and the scores on measurements of upper limb function and a QoL survey. The participant was assessed before and after 10 consecutive intervention sessions; in addition, the patient performed the training tasks in the workstation assisted by the FES device. Improvements in angles and time only in the affected wrist and enhancement in the Action Research Arm Test scores for both upper limbs were found after FES intervention. In addition, the patient's health-related QoL measurements improved. FES could ameliorate the proprioceptive deficit and the activity limitations of a stroke survivor. OXFORD LEVEL OF EVIDENCE: 3b; individual case control study. PMID- 27665395 TI - Infants anticipate probabilistic but not deterministic outcomes. AB - Infants look at physically impossible events longer than at physically possible events, and at improbable events longer than at probable events. Such behaviors are generally interpreted as showing that infants have expectations about future events and are surprised to see them violated. It is unknown, however, whether and under what conditions infants form proactive expectations about the future, as opposed to realizing post hoc that outcomes do not comply with their previous knowledge or experience. Here we investigate the relation between expectation and surprise at probabilistic or deterministic events in preverbal infants. When a situation is uncertain, 12-month-olds anticipate probable outcomes and are surprised at improbable continuations of the scene. However, they do not anticipate the only possible outcome of a physically deterministic situation, although they are surprised when it does not occur. The results suggest that infants are sensitive to the tradeoff between information gain and programming efforts, showing higher propensity to anticipate those future events that carry novel knowledge. PMID- 27665396 TI - Surprise capture and inattentional blindness. AB - Inattentional blindness (IB) is the phenomenon where unattended objects are not noticed. IB is typically tested within a surprise presentation procedure: A novel object is presented on a critical trial for the first time without prior announcement. Previous research indicates that IB is high unless the novel object is (a) similar to the target of the present task or (b) perceptually salient. The present study seeks evidence that the expectancy congruence of the novel object is a further important determinant of IB, and that the novel object is frequently noticed if it has a feature that is expectancy discrepant. An influence of perceptual saliency is excluded by presenting only two objects in each display. Experiment 1 reveals that an expectancy discrepant novel feature is noticed even if it is completely dissimilar to the target. Experiment 2 shows that expectancy discrepancy and match to target features can prioritize an object at the same time. Experiment 3 shows that IB is related to the degree of expectancy discrepancy. Results indicate that IB is prevented by two factors: match to target set and expectancy discrepancy. A revised model for IB is suggested. PMID- 27665397 TI - All cause mortality and body mass index in a young Asian occupational cohort without baseline metabolic syndrome components. AB - BACKGROUND: The aim was to investigate associations between underweight, overweight and obesity and all cause, cancer and cardiovascular disease (CVD) mortality, excluding subjects with known CVD, diabetes, hypertension and components of the metabolic syndrome (MetS) at baseline. METHODS: The study population consisted of examinees participating in a health screening in Korea from 2002 to 2013. Data were analyzed in 162,194 subjects (in a retrospective cohort study design-median (interquartile range (IQR) follow-up 4.9 (1.8 8.5years))). The outcomes were all cause mortality, cancer and CVD. RESULTS: The mean (age range) and median age (IQR) at baseline were 36.9(20.0-85.3) and 35.2 (30.8-40.6) years. There were 436 deaths during follow-up. For men and women together, the fully adjusted HR for underweight and all cause mortality, cancer and CVD was 1.53 (95% CIs 1.06-2.20), 1.21 (95% CIs 0.68-2.14) and 1.34 (95% CIs 0.40-4.49) respectively. In contrast, the fully adjusted HR for overweight/obesity combined and all cause mortality was 0.77 (95%CIs 0.63-0.95) and there were non significant trends towards decreased cancer and CVD mortality. The association between overweight/obesity and all cause mortality was similar for men and women considered separately and for overweight and obesity as separate BMI categories. Smoking did not seem to explain the increased HR in the underweight BMI category. CONCLUSIONS: In a young metabolically healthy adult cohort, underweight was associated with increased all cause mortality and overweight/obesity was associated with decreased all cause mortality if CVD, diabetes, hypertension and components of the metabolic syndrome (MetS) are excluded. PMID- 27665398 TI - Regional variation in coronary heart disease mortality trends in Portugal, 1981 2012. AB - BACKGROUND: Information is scarce about the geographic variation in time trends of mortality from coronary heart disease (CHD). We aimed to describe trends in death rates, absolute number of deaths and years of life lost (YLL) due to CHD among men and women in Portugal, by region, from 1981 to 2012. METHODS: The age standardized mortality rates from CHD were estimated by sex and region. We used joinpoint regression analysis to calculate the annual percent change (APC) in mortality and to identify points of significant change in the trend. The YLL due to premature mortality for CHD were computed using the Global Burden of Disease method. RESULTS: The age-adjusted mortality from CHD decreased between 1981 and 2012, both in men and women, but with significantly different APC by region. Smaller declines in rates were observed in Alentejo (men: APC 1993-2012: -2.4%; women: APC 1991-2012: -2.4%). The greatest decline was observed in Madeira between 2003 and 2012, in men (APC: -7.6%) and women (APC: -9.7%). The decline in rates in Algarve started only after 2003, whereas it was consistent from 1981 in the North and started in the 1990s in most other regions. A decrease in the number of deaths was only observed after 2000. The YLL from CHD decreased from 1981 to 2012, mainly after 2000. CONCLUSIONS: In Portugal, between 1981 and 2012, relative declines of CHD mortality indicators were different by geographic region. Consistent decreases in mortality rates were only observed in the Centre, Lisbon and North, the most populated and urbanized regions. PMID- 27665399 TI - Hyperuricemia and contrast-induced acute kidney injury: A systematic review and meta-analysis. AB - BACKGROUND: Hyperuricemia may be associated with an increased risk of contrast induced acute kidney injury (CI-AKI). In recent years, studies about the relationship between them gradually appeared. We performed a systematic review and meta-analysis to investigate whether hyperuricemia is an independent risk factor for CI-AKI. METHODS: Relevant studies were searched in PubMed, Embase, Cochrane Library, and CBM (Chinese Biomedical Literature database) databases until April 18, 2016, without language restriction. Observational studies evaluating serum uric acid (SUA) levels and CI-AKI risks were included. The pooled odds ratio was calculated to assess the association between hyperuricemia and risk of CI-AKI using a random-effects model. RESULTS: Eighteen relevant studies involving a total of 13,084 patients met our inclusion criteria. Presence of hyperuricemia was associated with an increased risk of CI-AKI development regardless of whether the effect size was adjusted or not (unadjusted OR: 2.08, 95% CI: 1.63-2.64; adjusted OR: 1.68, 95% CI: 1.38-2.04). In-hospital mortality and cases of renal replacement therapy were significantly different between subjects with hyperuricemia and normouricemia undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). CONCLUSION: Hyperuricemia is independently associated with the occurrence of CI-AKI and it significantly increases the in-hospital mortality and the risk of renal replacement therapy among the patients after CAG and/or PCI. Future research is needed to determine whether urate-lowering therapy has beneficial effects for reducing the incidence of CI-AKI and in-hospital adverse events. PMID- 27665400 TI - Is it time to change how we think about incomplete coronary revascularization? AB - The optimal degree of revascularization for patients with chronic multivessel coronary artery disease remains an unsolved issue. Intuitively, complete revascularization decreases cardiovascular events and improves outcomes compared to incomplete procedures, but in recent years the concept of incomplete revascularization moved from a sub-optimal or a defective treatment towards the most appropriate revascularization technique in some categories of patients. A reasonable level of incomplete anatomic revascularization has been shown to be safe and achievable with both percutaneous (PCI) and surgical procedures (CABG), despite with different long-term outcomes. What are the mechanisms underlying the clinical benefits of an incomplete revascularization and what are the factors explaining the discrepancy in the long-term clinical outcomes between the two modes of revascularization PCI and CABG? The biological consequences of coronary reperfusion might provide valuable hints in this context and at the same time cast new light on the way we think about incomplete revascularization. PMID- 27665401 TI - Dose-response relationship between serum uric acid levels and risk of incident coronary heart disease in the Dongfeng-Tongji Cohort. AB - BACKGROUND: In prospective studies, relationship of serum uric acid (SUA) with risk of coronary heart disease (CHD) incidence is inconsistent. We evaluated the association of SUA with incident CHD and the potential modifying effect of major CHD risk factors related to SUA among a middle aged and elderly Chinese population. METHODS: We included 16, 063 participants who were free of CHD, stroke, cancer and renal diseases at baseline from Sep. 2008 to June 2010, and were followed until Oct. 2013. Cox proportional hazard model was used to estimate the hazard ratios (HR) and 95% confidence interval (95% CI) of CHD incidence in relation to SUA. RESULTS: The adjusted HR for incident CHD increased gradually with the increasing SUA levels (P for linear trend=0.005), and the HR across sex specific SUA quartile was 1.26 (95% CI: 1.09, 1.47), 1.13 (95% CI: 0.97, 1.31), 1.23 (95% CI: 1.06, 1.43) and 1.00 (reference; P for trend=0.014), respectively. In particular, the association was more evident in individuals with normal-weight and those without hypertension or metabolic syndrome (all P for interactions<0. 05). CONCLUSIONS: These findings suggested that higher SUA levels were independently associated with a dose-response increased risk of CHD incidence. PMID- 27665402 TI - Impact of body mass index on long-term mortality in women and men undergoing percutaneous coronary intervention for chronic total occlusion. AB - BACKGROUND: The obesity paradox has been described in different patient populations. Data on the relation between obesity and outcomes in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) are lacking. Therefore, long-term mortality in patients undergoing CTO PCI was assessed according to different body mass index (BMI) categories. METHODS: A total of 1993 patients undergoing CTO PCI at a tertiary care center between January 2005 and December 2013 were divided into five different BMI categories: underweight, <18.5kg/m2; normal BMI, 18.5-24.9kg/m2; overweight, 25.0-29.9kg/m2; obese, 30.0-34.9kg/m2; and very obese, >=35.0kg/m2. The primary endpoint was all cause mortality. RESULTS: Median follow-up was 2.6 (interquartile range 1.1-3.1) years. Of the 1993 patients, 461 (23.1%) were of normal weight, 985 (49.4%) overweight, 396 (19.9%) obese, and 144 (7.2%) very obese. Compared with normal weight BMI patients (16.3%), overweight patients had a lower all-cause mortality (10.2%, Log Rank p=0.001), while obese (11.1%, Log Rank p=0.08) and severely obese (13.2%, Log Rank p=0.39) patients had similar mortality rates. Being overweight was significantly associated with a lower all-cause mortality (HR 0.69, 95% CI 0.53-0.89, p=0.005), and associations remained significant after multivariable adjustments for confounding factors (HR 0.73, 95% CI 0.56-0.95, p=0.02). While being overweight was linked with a reduced all-cause mortality in men (HR 0.65, 95% CI 0.48-0.88, p=0.005), it was not in women (HR 1.25, 95% CI 0.60-2.52, p=0.58). CONCLUSIONS: Overweight is associated with an improved survival in patients undergoing PCI for CTO, particularly in men. PMID- 27665404 TI - Review: The outcomes of different vessel diameter in patients receiving coronary artery stenting. AB - Compared to bare metal stent (BMS) implantation, drug-eluting stents (DES) is significantly better in attenuating intimal hyperplasia and reducing the rate of revascularization. However, the requirement of prolonged dual antiplatelet therapy (DAPT) and the economic cost have been the major disadvantages of DES. Studies have shown that the use of DES in small vessels decrease revascularization rate, but the results in large vessels vary. Previous studies have shown that the extent of late loss is unrelated to vessel diameter, and that late loss is easily accommodated in large vessels, thus resulting in decreased clinical benefit of DES in this setting. No definite cut-off point value of the vessel size has yet been demonstrated. Series studies aimed at evaluating the clinical outcomes of DES versus BMS in large vessels, but their results have been controversial. In this review, we evaluate the latest studies on clinical outcomes for different vessel sizes and clinical conditions. Nonetheless, further large clinical trials are warranted to address the clinical results of newer stents in different size vessels, especially in large vessels. PMID- 27665403 TI - miRNA-93-5p and other miRNAs as predictors of coronary artery disease and STEMI. AB - BACKGROUND: MicroRNAs (miRNAs), small non-coding RNAs, have been implicated as regulators of all mediators of atherosclerosis, and some reports have suggested increased levels in coronary artery disease (CAD) and acute myocardial infarction (AMI). However, the potential of miRNAs as biomarkers or predictors of disease remains to be established. METHODS: We designed a study comprising 150 patients (50 Control, 50 Stable CAD, and 50 ST Elevation Myocardial Infarction (STEMI)), and measured plasma miRNAs in each. We then determined the ability of differential miRNAs, adjusting for Framingham Heart Study (FHS) risk factors, to discriminate between CAD vs Control, and STEMI vs Control. RESULTS: Three miRNAs (miR15a-5p, miR16-5p, and miR93-5p) were significantly increased in Stable CAD vs Control groups and one (miR146a-5p) was significantly decreased in Stable CAD vs Control. One miRNA - miR499a-5p - was significantly increased in the STEMI group compared to Controls. After adjustment for FHS risk factors, miR93-5p levels remained an independent predictor of the presence of CAD (Odds Ratio [OR]=8.76, P=0.002). All 4 miRNAs improved discriminatory power for CAD over FHS alone in ROC analysis. Similarly, after adjustment for risk factors miR499-5p remained an independent predictor of STEMI (OR=3.03, P=0.001) and improved discriminatory power for STEMI in ROC analyses. CONCLUSION: We identified 4 miRNAs that were differentially expressed among stable CAD and control patients, and 1 miRNA that was elevated in STEMI patients vs controls. MiR93-5p was the strongest predictor of CAD after adjustment for traditional risk factors, suggesting potential diagnostic utility. PMID- 27665405 TI - Measuring senescence rates of patients with end-stage renal disease while accounting for population heterogeneity: an analysis of data from the ERA-EDTA Registry. AB - PURPOSE: Although a population's senescence rate is classically measured as the increase in mortality rate with age on a logarithmic scale, it may be more accurately measured as the increase on a linear scale. Patients on dialysis, who suffer from accelerated senescence, exhibit a smaller increase in their mortality rate on a logarithmic scale, but a larger increase on a linear scale than patients with a functioning kidney transplant. However, this comparison may be biased by population heterogeneity. METHODS: Follow-up data on 323,308 patients on dialysis and 91,679 patients with a functioning kidney transplant were derived from the ERA-EDTA Registry. We measured the increases in their mortality rates using Gompertz frailty models that allow individual variation in this increase. RESULTS: According to these models, the senescence rate measured as the increase in mortality rate on a logarithmic scale was smaller in patients on dialysis, while the senescence rate measured as the increase on a linear scale was larger in patients on dialysis than patients with a functioning kidney transplant. CONCLUSIONS: Also when accounting for population heterogeneity, a population's senescence rate is more accurately measured as the increase in mortality rate on a linear scale than a logarithmic scale. PMID- 27665406 TI - [Renal transplantation in 2046: Future and perspectives]. AB - OBJECTIVES: To report major findings that may build the future of kidney transplantation. MATERIAL AND METHODS: Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) database from 1960 to 2016 using the following keywords, in association, "bio engineering; heterotransplantation; immunomodulation; kidney; regenerative medicine; xenotransplantation". Articles were selected according to methods, language of publication and relevance. A total of 5621 articles were identified including 2264 for xenotransplantation, 1058 for regenerative medicine and 2299 for immunomodulation; after careful selection, 86 publications were eligible for our review. RESULTS: Despite genetic constructs, xenotransplantation faces the inevitable obstacle of species barrier. Uncertainty regarding xenograft acceptance by recipients as well as ethical considerations due to the debatable utilization of animal lives, are major limits for its future. Regenerative medicine and tridimensional bioprinting allow successful implantation of organs. Bioengineering, using decellularized tissue matrices or synthetic scaffold, seeded with pluripotent cells and assembled using bioreactors, provide exciting results but remain far for reconstituting renal complexity and vascular patency. Immune tolerance may be achieved through a tough initial T-cell depletion or a combined haplo-identical bone marrow transplant leading to lymphohematopoietic chimerism. CONCLUSION: Current researches aim to increase the pool of organs available for transplantation (xenotransplants and bio-artificial kidneys) and to increase allograft survival through the induction of immune tolerance. Reported results suggest the onset of a thrilling new era for renal transplantation providing end-stage renal disease-patients with an improved survival and quality of life. PMID- 27665407 TI - [Urologic malignancies in renal transplant candidates and recipients]. AB - OBJECTIVE: To review epidemiology and management of urologic neoplasms in renal transplant candidates and recipients. MATERIAL AND METHODS: Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) database using the following keywords, alone or in association, "neoplasms"; "prostate cancer"; "renal carcinoma"; "renal transplantation"; "transitional carcinoma"; "waiting list". Articles were selected according to methods, language of publication and relevance. A total of 7730 articles were identified including 781 for solid tumors, 1565 for renal cell carcinoma (RCC), 2674 for prostate cancer (Pca), 385 for transitional carcinoma (TC) and 56 for testicular cancer; after careful selection, 221 publications were eligible for our review. RESULTS: Renal transplant candidates and recipients are at higher risk of urologic neoplasms than general population, but prostate cancer has similar features. Thus, all therapeutic options are valid. Conversely to radiation therapy, radical prostatectomy provides precise staging and immediate affirmation of therapeutic success. Lymph nodes dissection needs to be discussed; systematic screening using PSA level and digital rectal examination should be offered in this specific population. RCC arising in native kidneys are usually low grade and stage and require total nephrectomy. In transplant candidates, there is no need to delay transplantation after treatment of low risk RCC according to published predictive nomograms. RCC of the allograft are rare, with a prevalence of 0.2 to 05% with a dialysis free survival ranging from 40 to 75% at 21.5 to 43 months. Treatment options are nephron sparing surgery, percutaneous ablation and immediate or deferred transplantectomy. Conversely to RCC or PCa, TC present with more unfavorable features as general population. Their management faces specific difficulties such as lower efficacy of BCG instillation or the technical challenge of urinary diversion. CONCLUSION: Application of appropriate indication for transplantectomy relies on benefit-risk balance between the interruption of immunosuppressive agents versus survival and quality of life impairment after returning to dialysis. No robust recommendation exists regarding switch of immunosuppressive drugs. Cancer predictive factors and access to a subsequent transplantation are key decisive elements. PMID- 27665408 TI - [Sexuality, fertility and pregnancy after kidney transplantation]. AB - AIMS: To describe sexuality and fertility alterations secondary to chronic kidney disease and their outcomes after renal transplantation. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords: erectile dysfunction; impotence; sexuality; pregnancy; fertility; renal transplantation. Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 706 articles. After reading titles and abstracts, 76 were included in the text, based on their relevance. RESULTS: The observed prevalence of erectile dysfunction is high in men with chronic kidney disease. The causes of erectile dysfunction are numbers and its origin is often multifactorial. Most of the time, kidney transplantation improves sexuality and the management of erectile dysfunction in transplanted men is similar to the general population. Improvement in sexuality in men and women after kidney transplantation may conduct to pregnancy. The outcomes of pregnancy after transplantation are quite good in absence of risk factors such as time to pregnancy less than 1 year after transplantation, uncontrolled high blood pressure, and decreased renal function of the graft. Adaptation of immunosuppression may be required to avoid any teratogenicity for the fetus. CONCLUSION: Kidney transplantation improves sexuality and fertility in men and women with chronic kidney disease. PMID- 27665409 TI - [The role of physicochemistry in urology and nephrology, selected results obtained during the last ten years]. AB - INTRODUCTION: The presence of pathological calcifications, which can be either concretions or ectopic call for physicochemical characterisation techniques in order to define a significant diagnosis. The aim of this review is to present a set of characterisation techniques able to describe at the micrometer scale their structural and chemical characteristics and show their place at the hospital. METHOD: Results already published in the last ten years based on characterisation techniques present in laboratories or specific to large-scale instruments are presented. Their usefulness for the clinician is discussed. RESULTS: The presence and role of heavy metals in urinary stones through data collected through MUX-ray fluorescence is debated. If these data suggest a simple substitution process of calcium, recent data suggest that weddellite is associated to a Zn-rich environment, partly favoured by an inflammation process. Investigation on the chemistry and the structure of unusual deposits in kidney biopsies show a great chemical diversity of ectopic calcifications. Such diversity shows that staining procedures to characterize such deposits are obsolete. Finally, several diseases which can be assessed through techniques specific to large-scale instruments and defined by the clinician are presented. CONCLUSION: The chemical and structural complexity of pathological calcifications call for a characterization through physicochemical techniques. Only such approach allows the clinician to define a significant diagnosis and to care the patient. PMID- 27665410 TI - [Polycystic kidney disease and kidney transplantation]. AB - OBJECTIVES: To perform a state of the art about autosomal dominant polykystic kidney disease (ADPKD), management of its urological complications and end stage renal disease treatment modalities. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): "autosomal dominant polykystic kidney disease", "complications", "native nephrectomy", "kidney transplantation". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 3779 articles. After reading titles and abstracts, 52 were included in the text, based on their relevance. RESULTS: ADPKD is the most inherited renal disease, leading to end stage renal disease requiring dialysis or renal transplantation in about 50% of the patients. Many urological complications (gross hematuria, cysts infection, renal pain, lithiasis) of ADPKD required urological management. The pretransplant evaluation will ask the challenging question of native nephrectomy only in case of recurrent kidney complications or large kidney not allowing graft implantation. The optimum timing for native nephrectomy will depend on many factors (dialysis or preemptive transplantation, complication severity, anuria, easy access to transplantation, potential living donor). CONCLUSION: Pretransplant management of ADPKD is challenging. A conservative strategy should be promoted to avoid anuria (and its metabolic complications) and to preserve a functioning low urinary tract and quality of life. When native nephrectomy should be performed, surgery remains the gold standard but renal arterial embolization may be a safe option due to its low morbidity. PMID- 27665411 TI - How parents and physicians experience end-of-life decision-making for children with profound intellectual and multiple disabilities. AB - BACKGROUND: End-of-life decisions (EoLD) often concern children with profound intellectual and multiple disabilities (PIMD). Yet, little is known about how parents and physicians discuss and make these decisions. AIMS: The objective of this research was to investigate the experiences of the parents and the involved physician during the end-of-life decision-making (EoLDM) process for children with PIMD. METHODS: In a retrospective, qualitative study, we conducted semi structured interviews with the physicians and parents of 14 children with PIMD for whom an EoLD was made within the past two years. RESULTS: A long-lasting relationship appeared to facilitate the EoLDM process, although previous negative healthcare encounters could also lead to distrust. Parents and physicians encountered disagreements during the EoLDM process, but these disagreements could also improve the decision-making process. Most parents, as well as most physicians, considered the parents to be the experts on their child. In making an EoLD, both parents and physicians preferred a shared decision-making approach, although they differed in what they actually meant by this concept. CONCLUSION: The EoLDM process for children with PIMD can be improved if physicians are more aware of the specific situation and of the roles and expectations of the parents of children with PIMD. PMID- 27665412 TI - Correlates of direct care staffs' attitudes towards aggression of persons with intellectual disabilities. AB - BACKGROUND AND AIM: To explain direct care staff's attitudes (responsive or rejecting) towards aggression of clients with intellectual disability (ID), data were collected about client characteristics as well as individual and team characteristics of 475 direct care staff members, working in 71 teams. METHOD AND RESULTS: Multilevel analyses revealed that a positive team climate was positively associated with both a rejecting and responsive attitude towards aggression. Senior staff members and females showed a less responsive attitude towards aggression, whereas a relatively high percentage of females in a team and a positive attitude towards external professionals were associated with a more responsive attitude towards aggression. Unexpectedly, staff who experienced less verbal and/or physical aggressive incidents of their clients with ID showed a more rejecting attitude towards aggression. Finally, characteristics of the clients with ID accounted for the largest part of the variance in the attitude towards aggression of direct care staff, in particular psychiatric diagnoses. CONCLUSIONS AND IMPLICATIONS: Further research is necessary in order to understand how team processes affect the attitude towards aggression of direct care staff. Further it is recommended to provide direct care staff with knowledge about mental disorders in clients with ID. PMID- 27665413 TI - High variability of individual longitudinal motor performance over five years in very preterm infants. AB - AIM: To determine longitudinal motor performance in very preterm (VPT) infants from 6 months to 5 years of age for the entire cohort of infants, according to gender and gestational age and at the individual level. METHOD: Single-center, prospective longitudinal study of 201 VPT infants (106 boys) without severe impairments. OUTCOMES: Motor performance was assessed with the Bayley Scales of Infant Development (BSID-II-MS: 6, 12, 24 months) and the Movement Assessment Battery for Children (MABC-2-NL: 5 years). RESULTS: At 6, 12, and 24 months and then at 5 years, 77%, 80%, 48%, and 22% of the infants, respectively, showed delayed motor performance (<-1SD). At 5 years, girls performed significantly better than boys in manual dexterity and balance. MIXED MODEL ANALYSES: that examined interactions between time and gender and time and gestational age, revealed no significant interactions. The variance at child level was 29%. Linear mixed model analysis revealed that mean z-scores of -1.46 at 6 months of age declined significantly to -0.52 at 5 years. Individual longitudinal motor performance showed high variability. IMPLICATIONS: Longitudinal motor performance improved almost 1 SD over five years. However, the variability of individual longitudinal motor performance hampers evaluation in clinical care and research. PMID- 27665414 TI - Co-variation between stressful events and rumination predicts depressive symptoms: An eighteen months prospective design in undergraduates. AB - Rumination is a maladaptive form of emotion regulation and seems to be the cognitive mechanism linking stress to depressive symptoms. However, it remains to be investigated whether individuals' variation in rumination in relation to the occurrence of stressful events (e.g., phasic co-variation between stressful events and rumination) prospectively predict the experience of depressive symptoms in lengthy follow-up moments. In this eighteen months prospective design, a large unselected sample of undergraduates was tested before, during, and after a period with prominent naturally occurring stressful events. The multilevel results show that the co-variation of stressful events and ruminative thinking predicts the experience of depressive symptoms at 3 and 15 months follow up moments, also when statistically controlling for baseline depressive symptoms. Moreover, the data demonstrate that the phasic elevations of rumination in relation to the occurrence of stressful events are more predictive of depressive symptoms compared with the stable aspects of rumination measured at one occasion. At the clinical level, the current findings seem to suggest a process-oriented intervention to target the phasic ruminative cognitions where individuals need to learn to control rumination exactly at moments of stress. PMID- 27665416 TI - How can the pressure in anti-embolism stockings be maintained during use? Laboratory evaluation of simulated 'wear' and different reconditioning protocols. AB - BACKGROUND: Deep vein thrombosis is a major global health issue, responsible for thousands of deaths each year. While thrombi can form under a variety of circumstances, lack of mobility significantly increases risk and therefore non ambulant patients are frequently fitted with anti-embolism stockings on admission to hospital, to aid blood flow, prevent pooling and thus clotting. Anti-embolism stockings are the most widely used non-invasive medical device on the market and are believed to reduce the risk of deep vein thrombosis by 40%. Despite their widespread use in hospitals world-wide, there is remarkably little research addressing their use or reconditioning and a wide variety of different reconditioning protocols are used in hospitals. OBJECTIVE: The objective of this study was to establish the impact of different wear and reconditioning protocols on the pressure delivering ability of anti-embolism stockings. DESIGN/METHODS: A laboratory investigation was undertaken to evaluate the pressure delivering ability of 2 major global brands of anti-embolism stockings over 5-8days of simulated wear (extension on static cylinders) and 4 different reconditioning protocols. 1 set of samples was continuously 'worn' for 8days without reconditioning, 1 set of samples was 'worn' for 5days with a day of relaxation between each day of 'wear', 1 set was 'hand washed' and 1 set was machine washed and then allowed to relax between each day of 'wear'. The pressure was measured at the beginning and end of each period of 'wear'. SETTING: This study was undertaken in a conditioned textile testing laboratory that complies with BS EN ISO 139:2005+A1:2011. RESULTS: The pressure exerted by anti-embolism stockings reduced by between 15 and 24% after 24h of wear, it reduced by between 21 and 32% when worn continuously for 8days. Allowing stockings to rest for a day between days of wear allowed them to recover slightly but this recovery was only temporary. Washing stockings regenerated their pressure delivering potential significantly and machine washing allowed some to recover to exert more pressure than they had when new. CONCLUSIONS: Different brands of anti-embolism stockings exert different pressures on the same size of leg, when correctly fitted. The pressure exerted by anti-embolism stockings decreases with use but the correct pressure gradient is maintained if correctly fitted. Washing stockings after 24h of wear is effective in restoring their pressure delivering abilities and in some cases can surpass their 'as new' pressure delivering ability. PMID- 27665415 TI - What good is labeling what's good? A field experimental investigation of parental labeled praise and child compliance. AB - There is a need to identify the "effective ingredients" of evidence-based behavior therapies. We tested the effects of one of the most common ingredients in parenting interventions for preventing disruptive child behavior, referred to as labeled praise (e.g., "well done picking up your toys"), which is typically recommended in preference to unlabeled praise (e.g., "well done"). We compared the effects of labeled praise, unlabeled praise, and no praise on child compliance in two experiments. Experiment 1 included 161 4 to 8 year-old community sample children and tested immediate effects of praise. Experiment 2 included 132 3 to 9 year-old children with varying levels of disruptive behavior and tested immediate and two-week effects of praise. In Experiment 1, teaching parents to use labeled praise did not increase immediate child compliance, whereas teaching them to use unlabeled praise did. In Experiment 2, teaching parents to use labeled praise for two weeks reduced disruptive child behavior, but this effect was of a similar magnitude to that for unlabeled praise. Parents preferred the use of unlabeled over labeled praise. These findings suggest that parental praise promotes child compliance, but the addition of labeling the specific positive behavior may not be of incremental value. PMID- 27665418 TI - Physical and social factors associated with early adolescent headache and stomachache pain. AB - PURPOSE: Approximately one third of adolescents in the United States report experiencing frequent headaches and stomachaches. We examined the association of psychosocial and physical factors with the report of weekly headaches or stomachaches using a representative sample of US teens. METHODS: Data for this project are from the survey of Health Behavior in School-Aged Children (HBSC), 2005-2006, a nationally representative sample of students in grades 6-10 in the United States. The total sample includes 12,070 students aged 11-17. Using logistic regression we modeled chronic headache and stomachache separately with the same set of physical predictors (dieting and substance use habits) and psychosocial predictors (attitudes towards self-image, peers, and family) along with demographic controls. RESULTS: Almost 20% of respondents experienced headaches weekly, and 12% experienced abdominal pain. Both physical and psychosocial factors were predictive of chronic symptoms. Increased substance usage and unhealthy eating practices were associated with the likelihood of experiencing both headaches and stomachaches. Negative self-image, family relationships, and school life were also predictive of symptom frequency. CONCLUSION: Headaches and stomachaches are associated with poor eating and substance use habits, as well as problems with self-image or social relationships among adolescents. For health care professionals, a holistic approach is needed to effectively address symptoms and prevent long-term health problems. PMID- 27665417 TI - Fetal echocardiography: reference values for the Chinese population. AB - OBJECTIVE: Global racial variability in human development can lead to differences in size of fetal cardiac structures during gestation. Our objective is to establish normal reference ranges of fetal cardiac dimensions between 20 and 34 weeks from fetal echocardiograms recorded at a single center in China. METHODS: A prospective cross-sectional study was undertaken on single pregnancies with normal fetuses of varying gestational ages (GAs). A total of 4396 normal fetuses were divided into 15 groups from 20 to 34 weeks according to the GA. Measurements included the inner diameter of the fetal cardiac chambers and arteries, the aortic arch isthmus (AI), the descending aorta (DAO), the ductus arteriosus (DA), and the foramen ovale (FO). Measurements were statistically analyzed and regression analysis was applied to assess for correlation with GA. RESULTS: Normal reference values of fetal cardiovascular dimensions between 20 and 34 weeks were obtained from 4396 subjects at a single center in China. Measurements of fetal cardiac structures increase with advancing GA. It seems there is no difference in r values among linear, cubic, and quadratic model analyses (P > 0.05). However, the r values for the exponential models appear to be smaller than those of the other three models (P < 0.05). Ratios of the diameters of fetal cardiac structures were calculated in order to identify for differential changes in the growth of structures. CONCLUSIONS: The presented data derived from 4396 normal fetuses provide the reference values of fetal echocardiography in China, which provide guidance to fetal echocardiography examinations. PMID- 27665419 TI - Brain metabolic DNA in memory processing and genome turnover. AB - Sophisticated methods are currently used to investigate the properties of brain DNA and clarify its role under physiological conditions and in neurological and psychiatric disorders. Attention is now called on a DNA fraction present in the adult rat brain that is characterized by an elevated turnover and is not involved in cell division or DNA repair. The fraction, known as brain metabolic DNA (BMD), is modulated by strain, stress, circadian oscillations, exposure to enriched or impoverished environment, and notably by several training protocols and post trial sleep. BMD is frequently localized in glial cells but is also present in neurons, often in the perinucleolar region. Its distribution in repetitive and non-repetitive DNA fractions shows that BMD differs from native DNA and that in learning rats its profile differs from that of control rats. More detailed knowledge of the molecular, cellular, and time-dependent BMD features will be necessary to define its role in memory acquisition and processing and in the pathogenesis of neurologic disorders. PMID- 27665421 TI - Massive interference in free T4 and free T3 assays misleading clinical judgment. PMID- 27665420 TI - Exercise increases the level of plasma orexin A in humans. AB - BACKGROUND: The purpose of this research was to study the effects of exercise on the concentration of plasma orexin A, a peptide regulating several physiological functions. METHODS: Blood samples were collected from participants (men, n=10; age: 24.4+/-2.93 years) 15, 0 min before the start of exercise, and 30, 45, 60 min after a cycle ergometer exercise at 75 W for 15 min. Also heart rate (HR), galvanic skin response (GSR), and rectal temperature were monitored. RESULTS: The exercise induced a significant increase (p<0.01) in plasmatic orexin A with a peak at 30 min after the exercise bout, in association with an increase of the other three monitored variables: HR (p<0.01), GSR (p<0.05), and rectal temperature (p<0.01). CONCLUSIONS: Our findings indicate that plasmatic orexin A is involved in the reaction to physical activity. PMID- 27665422 TI - Comparison of three routine insulin immunoassays: implications for assessment of insulin sensitivity and response. PMID- 27665423 TI - Detection of BRAFV600K mutant tumor-derived DNA in the pleural effusion from a patient with metastatic melanoma. PMID- 27665424 TI - The prevalence of hemolysis - a survey using hemolysis index. PMID- 27665425 TI - Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity. AB - BACKGROUND: New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this. MATERIALS AND METHODS: This narrative review, largely based on recent systematic reviews and meta analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction. RESULTS AND CONCLUSIONS: All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%-11% of pre-surgical values) and weakest for dietary restriction (1%-1.5% of pre-treatment values). Weight loss pharmaceuticals (orlistat or the glucagon-like peptide-1 receptor agonist, liraglutide) induced no greater changes from pre-treatment values than control, despite greater weight loss. There is suggestive evidence that liraglutide may increase bone mineral content (BMC) - but not BMD - and reduce fracture risk, but more research is required to clarify this. All three obesity treatments have variable effects on spine BMD, probably due to greater measurement error at this site in obesity, suggesting that future research in this field could focus on hip rather than spine BMD. Various mechanisms have been proposed for BMD loss with obesity treatments, notably reduced nutritional intake/absorption and insufficient exercise, and these are potential avenues for protection against bone loss. However, a pressing outstanding question is whether this BMD reduction contributes to increased fracture risk, as has been observed after RYGB, and whether any such increase in fracture risk outweighs the risks of staying obese (unlikely). PMID- 27665427 TI - Variability of 137Cs inventory at a reference site in west-central Iran. AB - 137Cs technique has been widely used for the evaluation rates and patterns of soil erosion and deposition. This technique requires an accurate estimate of the values of 137Cs inventory at the reference site. This study was conducted to evaluate the variability of the inventory of 137Cs regarding to the sampling program including sample size, distance and sampling method at a reference site located in vicinity of Fereydan district in Isfahan province, west-central Iran. Two 3 * 8 grids were established comprising large grid (35 m length and 8 m width), and small grid (24 m length and 6 m width). At each grid intersection two soil samples were collected from 0 to 15 cm and 15-30 cm depths, totally 96 soil samples from 48 sampling points. Coefficients of variation for 137Cs inventory in the soil samples was relatively low (CV = 15%), and the sampling distance and methods used did not significantly affect the 137Cs inventories across the studied reference site. To obtain a satisfactory estimate of the mean 137Cs activity in the reference sites, particularly those located in the semiarid regions, it is recommended to collect at least four samples along in a grid pattern 3 m apart. PMID- 27665426 TI - Managing stress in prehospital care: Strategies used by ambulance nurses. AB - BACKGROUND: Ambulance nurses display stress symptoms, resulting from their work with patients in an emergency service. Certain individuals seem, however, to handle longstanding stress better than others and remain in exposed occupations such as ambulance services for many years. This paper examines stress inducing and stress defusing factors among ambulance nurses. METHODS: A qualitative descriptive design using critical incident technique was used. A total of 123 critical incidents were identified, and a total of 61 strategies dealing with stress were confirmed. In all, 13 sub-categories (seven stress factors and five stress reducing factors) were merged into four categories (two stress categories and two stress reducing categories). RESULTS AND CONCLUSION: The study shows that ambulance nurses in general experience emergency calls as being stressful. Unclear circumstances increase the stress level, with cases involving children and childbirth being especially stressful. Accurate information and assistance from the dispatch centre reduced the stress. Having discussions with colleagues directly after the assignment were particularly stress reducing. Advanced team collaboration with teammates was viewed as effective means to decrease stress, in addition to simple rituals to defuse stress such as taking short breaks during the workday. The study confirmed earlier studies that suggest the benefits of defusing immediately after stress reactions. PMID- 27665429 TI - Wide-range tunable magnetic lens for tabletop electron microscope. AB - A tabletop scanning electron microscope (SEM) utilizes permanent magnets as condenser lenses to minimize its size, but this sacrifices the tunability of condenser lenses such that a tabletop system can only be operated with a fixed accelerating voltage. In contrast, the traditional condenser lens utilizes an electromagnetic coil to adjust the optical properties, but the size of the electromagnetic lens is inevitably larger. Here, we propose a tunable condenser lens for a tabletop SEM that uses a combination of permanent magnets and electromagnetic coils. The overall dimensions of the newly designed lens are the same as the original permanent magnet lens, but the new lens allows the tabletop SEM to be operated at different accelerating voltages between 1kV and 15kV. PMID- 27665428 TI - Angle selective backscattered electron contrast in the low-voltage scanning electron microscope: Simulation and experiment for polymers. AB - Recently developed detectors can deliver high resolution and high contrast images of nanostructured carbon based materials in low voltage scanning electron microscopes (LVSEM) with beam deceleration. Monte Carlo Simulations are also used to predict under which exact imaging conditions purely compositional contrast can be obtained and optimised. This allows the prediction of the electron signal intensity in angle selective conditions for back-scattered electron (BSE) imaging in LVSEM and compares it to experimental signals. Angle selective detection with a concentric back scattered (CBS) detector is considered in the model in the absence and presence of a deceleration field, respectively. The validity of the model prediction for both cases was tested experimentally for amorphous C and Cu and applied to complex nanostructured carbon based materials, namely a Poly(N isopropylacrylamide)/Poly(ethylene glycol) Diacrylate (PNIPAM/PEGDA) semi interpenetration network (IPN) and a Poly(3-hexylthiophene-2,5-diyl) (P3HT) film, to map nano-scale composition and crystallinity distribution by avoiding experimental imaging conditions that lead to a mixed topographical and compositional contrast. PMID- 27665430 TI - The mechanism for bacteriophage f2 removal by nanoscale zero-valent iron. AB - Nanoscale zero-valent iron (NZVI) has shown excellent performance for pathogenic microorganism removal but the inactivation mechanism has not been understood clearly enough. In this study, the bacteriophage f2 removal by NZVI under aerobic and anaerobic conditions was investigated, and various factors involved in f2 removal were analyzed in detail, including the ion products of NZVI (Fe(II), Fe(III)), solid phase products, the reactive oxygen species (ROS), O2 and H+. In addition, the morphologies of bacteriophage f2 during reaction were observed. The results showed that the removal efficiency of bacteriophage f2 was much higher under aerobic conditions than that in anaerobic systems, and oxygen and pH were determinants for f2 removal. The oxidation of Fe(II) was a fundamental step and played a significant role in bacteriophage f2 removal, especially in the aerobic systems. In the presence of oxygen, the virus removal was attributed to the generation of ROS (namely .OH and .O2-) and the oxidized iron, in which the ROS (.OH and .O2-) made a predominant contribution. And the adsorption of iron oxide was responsible for the removal in oxygen depleted circumstance. In the anaerobic system, the virus removal was mainly attributed to the interaction between NZVI and bacteriophage f2. Besides, from the perspective of TEM images, the virus removal was mainly attributed to the damage of infective ability by NZVI at the initial stage of reaction, and later the virus was inactivated by the ROS generated. PMID- 27665431 TI - Platinum recovery from industrial process streams by halophilic bacteria: Influence of salt species and platinum speciation. AB - The increased use and criticality of platinum asks for the development of effective low-cost strategies for metal recovery from process and waste streams. Although biotechnological processes can be applied for the valorization of diluted aqueous industrial streams, investigations considering real stream conditions (e.g., high salt levels, acidic pH, metal speciation) are lacking. This study investigated the recovery of platinum by a halophilic microbial community in the presence of increased salt concentrations (10-80 g L-1), different salt matrices (phosphate salts, sea salts and NH4Cl) and a refinery process stream. The halophiles were able to recover 79-99% of the Pt at 10-80 g L 1 salts and at pH 2.3. Transmission electron microscopy suggested a positive correlation between intracellular Pt cluster size and elevated salt concentrations. Furthermore, the halophiles recovered 46-95% of the Pt-amine complex Pt[NH3]42+ from a process stream after the addition of an alternative Pt source (K2PtCl4, 0.1-1.0 g L-1 Pt). Repeated Pt-tetraamine recovery (from an industrial process stream) was obtained after concomitant addition of fresh biomass and harvesting of Pt saturated biomass. This study demonstrates how aqueous Pt streams can be transformed into Pt rich biomass, which would be an interesting feed of a precious metals refinery. PMID- 27665432 TI - Effects of ozone pretreatment and operating conditions on membrane fouling behaviors of an anoxic-aerobic membrane bioreactor for oil sands process-affected water (OSPW) treatment. AB - Two identical anoxic-aerobic membrane bioreactors (MBRs) were operated in parallel for 742 consecutive days for raw and ozonated oil sands process-affected water (OSPW) treatment. The MBRs not only substantially degraded OSPW classical and oxidized NAs, but also demonstrated outstanding membrane fouling control performance (the MBR receiving raw OSPW experienced its first severe fouling with a transmembrane pressure (TMP) of -35 kPa on Day 433). The mild ozonation (30 mg O3/L) pretreatment of OSPW remarkably enhanced OSPW NA degradation, and improved the MBR's fouling control in terms of prolonged long-term slow TMP growth phase and reduced TMP jump frequency. Ozonation substantially altered the feed water organic composition, reshaped the microbial community (e.g., reduced growth of extracellular polymeric substances (EPS) producers and biofilm formation facilitators), and lowered EPS production and EPS protein/polysaccharides (PN/PS) ratio, consequently leading to the better fouling control. Examination on fouling behaviors at different HRTs of the raw OSPW MBR indicates that HRT also played a role in determining the dominating fouling mechanism during the sharp TMP rise phase. Therefore, the results of this study suggest that the low-dose ozone pretreatment is a good option to enhance organic contaminant degradation and alleviate membrane fouling in the MBR for OSPW treatment. PMID- 27665433 TI - Human polyomavirus: Advantages and limitations as a human-specific viral marker in aquatic environments. AB - Human polyomaviruses (HPyVs) cause persistent infections in organs such as kidney, brain, skin, liver, respiratory tract, etc., and some types of HPyV are constantly excreted in the urine and/or feces of infected and healthy individuals. The use of an enteric virus as an indicator for human sewage/waste contamination in aquatic environments has been proposed; HPyVs are a good candidate since they are routinely found in environmental water samples from different geographical areas with relatively high abundance. HPyVs are highly human specific, having been detected in human waste from all age ranges and undetected in animal waste samples. In addition, HPyVs show a certain degree of resistance to high temperature, chlorine, UV, and low pH, with molecular signals (i.e., DNA) persisting in water for several months. Recently, various concentration methods (electronegative/positive filtration, ultrafiltration, skim milk flocculation) and detection methods (immunofluorescence assay, cell culture, polymerase chain reaction (PCR), integrated cell culture PCR (ICC-PCR), and quantitative PCR) have been developed and demonstrated for HPyV, which has enabled the identification and quantification of HPyV in various environmental samples, such as sewage, surface water, seawater, drinking water, and shellfish. In this paper, we summarize these recent advancements in detection methods and the accumulation of environmental surveillance and laboratory-scale experiment data, and discuss the potential advantages as well as limitations of HPyV as a human-specific viral marker in aquatic environments. PMID- 27665434 TI - Quercetin modulates toll-like receptor-mediated protein kinase signaling pathways in oxLDL-challenged human PBMCs and regulates TLR-activated atherosclerotic inflammation in hypercholesterolemic rats. AB - Toll-like receptors (TLRs) are pattern recognition receptors that have a unique and essential function in innate immunity. The effect of quercetin on TLR mediated downstream signaling mechanism and its effect on TLR-mediated MAP kinase and Akt pathways were studied in oxLDL-stimulated hPBMCs using specific inhibitors. The pretreatment of hPBMCs with specific TLR inhibitor, CLI-095, decreased the NF-kappaB nuclear translocation and TNF-alpha release by oxLDL. When the cells treated with inhibitor and quercetin together, the inhibition was more effective. The specific inhibitor for p38 MAPK, SB203580, reduced the phosphorylated p38 level and decreased the NF-kappaB activation and TNF-alpha release by oxLDL-challenged hPBMCs. This inhibitor showed enhanced inhibition when treated with quercetin together. The inhibitors for ERK1/2, PD98059, and for JNK, SP606125, also showed inhibitory effect on NF-kappaB activation and TNF alpha release by oxLDL-simulated hPBMCs. Quercetin supplementation enhanced the inhibition of nuclear translocation of NF-kappaB and the release of cytokines. TLR4 inhibition study confirmed the downstream signaling mechanism mediated by NF kappaB which is involved in the oxLDL-induced inflammatory response, and quercetin suppresses the cytokine, TNF-alpha release by modulating TLR-NF-kappaB signaling pathway. In addition to NF-kappaB signaling pathway, inflammation induced by oxLDL was also related to the activation of p38MAPK, ERK1/2 and JNK, and Akt pathways, and the protective effect of quercetin may be also related to the inhibition of activation of these pathways. Quercetin significantly downregulated the elevated mRNA expression of TLRs and cytokine TNF-alpha in HCD fed atherosclerotic rats in vivo. As quercetin possesses inhibition on both TLR NF-kappaB signaling pathway and TLR-mediated MAPK pathway, it is evident that it can be used as a therapeutic agent to ameliorate atherosclerotic inflammation. Since quercetin is the major flavonoid and forms the backbone of many other flavonoids and this study provides strong evidence that it has potent anti inflammatory effect, quercetin may be a promising agent for the prevention and treatment of atherosclerosis and promote health by reducing harmful vascular inflammation. PMID- 27665436 TI - Metaphilosophy of Mind: how Do Minds Investigate Minds? Refutation of the Theocentric View. AB - I shall propose metaphilosophy of mind as the philosophy of mind investigating mind. That is to say, I pose the question of how knowledge of mind provided by cognitive science, broadly construed, is constrained by the epistemic position of the knower, i.e. by the very fact that it is undertaken by a mind. Here I would like to propose a minimal framework, based on two distinctions: (i) the standard one between empirical and conceptual analysis; (ii) a new one, between the internal questions of mind and the boundary questions of mind. I shall then combine these distinctions to arrive at several ways of investigating the mind, the brain and cognition. On this ground, I will discuss the notion of epistemological theocentrism as outlined by Henry Allison and argue against the perspective I call theocentric philosophy of mind. From this angle I will be able to address skepticism which cannot be defeated but actually can be, as I put it, disarmed. Finally, metaphilosophy of mind based on the abovementioned distinctions elicits a perspective that is not sufficiently delineated by cognitive scientists and philosophers: empirical way of addressing the boundary questions of mind. PMID- 27665437 TI - "How long will I have my ACE?": report of the pediatric colorectal club meeting, Prague June 11-13, 2016. PMID- 27665435 TI - Risk factors for fatigue among airline pilots. AB - PURPOSE: The objective of this study is to determine risk factors for fatigue among airline pilots, taking into account person-, work-, health-, sleep-, and lifestyle-related characteristics. METHODS: The study population consisted of 502 pilots who participated in the MORE Energy study. Included risk factors were either measured through an online questionnaire or provided by the company. The outcome of this study, fatigue, was assessed using the Checklist Individual Strength (CIS), and was defined as scoring more than 76 points on this questionnaire. The association of the risk factors with fatigue was determined using univariate and multivariate logistic regression analyses. RESULTS: Of the participating pilots, 29.5 % scored more than 76 points on the CIS and were classified as being fatigued. The fully adjusted regression model showed that person-, work-, health-, and lifestyle-related characteristics were associated with fatigue. Pilots who were aged 31 to 40 (OR 3.36, 95 % CI 1.32-8.53) or 41 to 50 (OR 4.19, 95 % CI 1.40-12.47), an evening type (OR 2.40, 95 % CI 1.38-4.16), scored higher on work-life balance disturbance (OR 1.22, 95 % CI 1.10-1.36), scored higher on need for recovery (OR 1.02, 95 % CI 1.01-1.04), scored lower on general health perception (OR 0.31, 95 % CI 0.20-0.47), were less physically active (OR 0.77, 95 % CI 0.66-0.89), and had a moderate alcohol consumption (OR 3.88, 95 % CI 1.21-12.43), were at higher risk for fatigue. CONCLUSIONS: Higher age, being an evening type, disturbance of the work-life balance, more need for recovery, a lower perceived health, less physical activity, and moderate alcohol consumption were shown to be risk factors for fatigue. Further longitudinal research is needed to elucidate the direction of the associations found and to evaluate the effects of possible countermeasures in airline pilots. PMID- 27665438 TI - Biventricular takotsubo cardiomyopathy in an elderly woman with uncontrolled type 2 diabetes: the biphasic echocardiographic and clinical pattern. AB - We describe a case of an elderly woman who was diagnosed with a biventricular takotsubo cardiomyopathy (TTC) with combination of emotional stress and poorly controlled type 2 diabetes. We observed significant correlation between biphasic improvement of right (after 4 days) and left ventricle function (after 4 weeks) with normalization glycemic status. To our knowledge, this is the first reported case in the literature of biventricular TTC with such metabolic disturbances. PMID- 27665439 TI - The association between sleep duration, snoring and prevalent type 2 diabetes mellitus with regard to gender and menopausal status: the CKB study in Zhejiang rural area, China. AB - AIMS: To evaluate the association between sleep duration, snoring and diabetes according to gender and menopausal status in rural China. METHODS: The data were part of the baseline survey of China Kadoorie Biobank, from a rural county in the south-east costal Zhejiang province. Participants including 24,027 men and 33,677 women aged 30-79 years were enrolled during 2004-2008. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetes. RESULTS: Sleep duration was shown to have a U shaped association with diabetes in women, in particular in postmenopausal women after adjustment for potential confounders. Compared with 7-h sleepers, ORs (95 % CIs) of sleep duration <=5 and >=10 h for diabetes were 1.32 (1.02-1.69) and 1.30 (1.03-1.65), respectively, in postmenopausal women (P for quadratic trend = 0.016). However, this U-shaped association was not obvious in men and premenopausal women. Frequently snoring was positively associated with diabetes in all participants. However, this association was not independent of socioeconomic status, health behaviors, obesity and chronic diseases. With increasing sleep duration, the proportion of frequently snoring increased in all participants (P trend <0.05). Postmenopausal women had 23 % (95 % CI 6-44 %) higher odds of diabetes compared with premenopausal women, and the duration of menopause had cumulative effects on diabetes. CONCLUSIONS: Short and long sleep durations were significantly associated with diabetes in postmenopausal women, independent of potential confounders. The proportion of frequently snoring had linear trend with sleep duration. Postmenopausal status and the duration of menopause increased the odds of diabetes. PMID- 27665440 TI - Planetary Overload, Limits to Growth and Health. AB - Since the use of atomic weapons in 1945 visionaries have warned that without major changes the survival of global civilization is in question. These concerns deepened in following decades, during the Cold War, with The Limits to Growth, the best-selling environmental book of the 1970s. Yet, since then, most concern has faded, fuelled by technological developments and a shift in dominant global ideology. Public health, with a few exceptions (one of which is the book Planetary Overload), has been slow to recognize this debate, even as evidence emerges that civilization may indeed be at risk, driven by an increasingly ominous complex of events. This article outlines the key relevant literature and concepts, attempting to bring emerging and future health consequences to the attention of health workers, including the idea of a "social vaccine," conveying sufficient anxiety to provoke action for environmental protection, but insufficient to induce paralysis. PMID- 27665441 TI - Prognostic value of the Glasgow Prognostic Score in renal cell carcinoma: a meta analysis. AB - PURPOSE: Glasgow Prognostic Score (GPS) has been reported to predict oncologic outcomes in various type of cancer. However, their prognostic value in patients with renal cell carcinoma (RCC) is unclear. In this meta-analysis, we evaluated the prognostic significance of GPS in RCC patients. METHODS: We performed comprehensive searches of electronic databases to identify studies that evaluated the prognostic impact of pretreatment GPS in RCC patients. The end points were cancer-specific survival (CSS), recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) or odds ratios with 95 % confidence intervals (CIs). RESULTS: Nine retrospective, observational, cohort studies involving 2096 patients were included. Seven studies evaluated CSS, and three evaluated RFS. Our results showed that higher GPS (0 vs. 1 vs. 2) was significantly predictive of poorer CSS (HR 3.68, 95 % CI 2.52-5.40, p < 0.001) and RFS/DFS (HR 2.83, 95 % CI 1.86-4.30, p < 0.001) in patients with RCC. These findings were robust when stratified by sample size, presence of metastasis, and study region. We also conducted subgroup analysis by assessment of Newcastle-Ottawa quality assessment scale (NOS) score, and the HRs were 2.708 (95 % CI 1.969, 3.725) in under 7 points group, 3.685 (95 % CI 2.516, 5.396) in over than 7 points group in CSS. Meta-regression analysis indicated that NOS score group had a significant difference in HRs (p = 0.032). CONCLUSIONS: Higher GPS is associated with tumor progression and is predictive of poorer survival in patients with RCC. Therefore, GPS may help to inform treatment decisions and predict treatment outcomes. PMID- 27665442 TI - Inactivation of E. coli by nano-Cu/MWCNTs combined with hydrogen peroxide. AB - This paper aims at the study on the antibacterial activity of nCu-MWCNTs combined with H2O2 against gram-negative bacteria Escherichia coli (E. coli). The antibacterial ability of nCu-MWCNTs/H2O2 was evaluated by traditional surface plating method, fluorescence and SEM imaging, and the effects of variables (contacting time, dose of nCu-MWCNTs and dose of H2O2) were investigated. By comparing with other five processes including H2O2, MWCNTs, nCu-MWCNTs, MWCNTs/H2O2 and nCu/H2O2, nCu-MWCNTs and H2O2 was proved to have superlative antimicrobial effectiveness against E. coli. The role of nano-Cu, MWCNTs and H2O2 in the antimicrobial activity of nCu-MWCNTs/H2O2 was clarified. The release of copper ions and formation of hydroxyl radicals (OH) both contributed the antibacterial ability of nCu-MWCNTs/H2O2 system. And MWCNTs as the support might be able to promote the electron transfer in nCu-MWCNTs for copper ion release. PMID- 27665443 TI - Assessment of diet-related GHG emissions using the environmental hourglass approach for the Mediterranean and new Nordic diets. AB - Food production and preparation affect the environment in many ways, with effects on greenhouse gases, use of land, biodiversity, etc. The impact is influenced by consumer demand and eating habits. Two different recommended dietary models were considered, the Mediterranean Diet and the New Nordic Diet, with quantitative analysis of GHG emissions through LCA. An environmental hourglass (EH) approach based on LCA was introduced to help translate health-promoting dietary recommendations that consider regional circumstances and cultural diversity into practical eating habits, to promote sustainable and environmentally friendly consumption. Using the environmental hourglass approach, we examined whether dietary choices based on nutritional recommendations can minimise certain negative effects on the food production environment. Using two examples of health enhancing, regionally-oriented and culturally appropriate dietary patterns - the Mediterranean Diet and the New Nordic Diet - we showed that consumption of high protein foods has a similar and comparable environmental impact to fruit and vegetable consumption. The results of this work may provide a starting point for integrated policy addressing issues related to the healthy diet of the population, aware food choices and sustainable agriculture. PMID- 27665444 TI - Sensitivity of health sector indicators' response to climate change in Ghana. AB - There is accumulating evidence that the emerging burden of global climate change threatens the fidelity of routine indicators for disease detection and management of risks to public health. The threat partially reflects the conservative character of the health sector and the reluctance to adopt new indicators, despite the growing awareness that existing environmental health indicators were developed to respond to risks that may no longer be relevant, and are too simplistic to also act as indicators for newer global-scale risk factors. This study sought to understand the scope of existing health indicators, while aiming to discover new indicators for building resilience against three climate sensitive diseases (cerebro spinal meningitis, malaria and diarrhea). Therefore, new potential indicators derived from human and biophysical origins were developed to complement existing health indicators, thereby creating climate sensitive battery of robust composite indices of resilience in health planning. Using Ghana's health sector as a case study systematic international literature review, national expert consultation, and focus group outcomes yielded insights into the relevance, sensitivity and impacts of 45 indicators in 11 categories in responding to climate change. In total, 65% of the indicators were sensitive to health impacts of climate change; 24% acted directly; 31% synergistically; and 45% indirectly, with indicator relevance strongly associated with type of health response. Epidemiological indicators (e.g. morbidity) and health demographic indicators (e.g. population structure) require adjustments with external indicators (e.g. biophysical, policy) to be resilient to climate change. Therefore, selective integration of social and ecological indicators with existing public health indicators improves the fidelity of the health sector to adopt more robust planning of interdependent systems to build resilience. The study highlights growing uncertainties in translating research into protective policies when new indicators associated with non-health sources are needed to complement existing health indicators that are expected to respond to climate change. PMID- 27665445 TI - Multi-tool assessment of trace metals in mangroves combining sediment and clam sampling, DGT passive samplers and caged mussels. AB - The rapid loss of mangroves globally has triggered a call for a better understanding of this habitat, including its dynamics and the threats it is exposed to. The present paper reports the study of trace metals at nine mangrove sites in Singapore in 2012/2013, using the simultaneous application of various tools, namely sediment analyses, the technique of diffusive gradients in thin films (DGT) and caged/native bivalves (for both chemical and biomarker analyses). DGT devices were successfully deployed over 28days in tropical mangrove waters, and the concentration measured with DGT showed significant correlation with the accumulation for Cu, Zn and Cd in caged mussels, and Cu for native clams, supporting the relevance of DGT to predict metal bioaccumulation. Concentrations in mangrove sediment are reported for As, Cd, Co, Cr, Cu, Ni, Pb and Zn. Sediment levels on a dry weight (dw) basis of Cu (ND-219.5MUg/g dw) and Zn (ND-502MUg/g dw) exceeded general sediment quality criteria at two sites. Most notably for these two metals, investigations based on the four tools (DGT, sediments, caged mussels and clams) were all able to segregate sites above and below the sediment quality guideline. This was further supported by a range of significant linear correlations between the measurements obtained with the various tools. The present findings support that these monitoring tools are comparable in the field to provide a time-integrated assessment of metals such as Cu and Zn. PMID- 27665446 TI - Delivering organisational adaptation through legislative mechanisms: Evidence from the Adaptation Reporting Power (Climate Change Act 2008). AB - There is increasing recognition that organisations, particularly in key infrastructure sectors, are potentially vulnerable to climate change and extreme weather events, and require organisational responses to ensure they are resilient and adaptive. However, detailed evidence of how adaptation is facilitated, implemented and reported, particularly through legislative mechanisms is lacking. The United Kingdom Climate Change Act (2008), introduced the Adaptation Reporting Power, enabling the Government to direct so-called reporting authorities to report their climate change risks and adaptation plans. We describe the authors' unique role and experience supporting the Department for Environment, Food and Rural Affairs (Defra) during the Adaptation Reporting Power's first round. An evaluation framework, used to review the adaptation reports, is presented alongside evidence on how the process provides new insights into adaptation activities and triggered organisational change in 78% of reporting authorities, including the embedding of climate risk and adaptation issues. The role of legislative mechanisms and risk-based approaches in driving and delivering adaptation is discussed alongside future research needs, including the development of organisational maturity models to determine resilient and well adapting organisations. The Adaptation Reporting Power process provides a basis for similar initiatives in other countries, although a clear engagement strategy to ensure buy-in to the process and research on its long-term legacy, including the potential merits of voluntary approaches, is required. PMID- 27665447 TI - Virulence and biodegradation potential of dynamic microbial communities associated with decaying Cladophora in Great Lakes. AB - Cladophora mats that accumulate and decompose along shorelines of the Great Lakes create potential threats to the health of humans and wildlife. The decaying algae create a low oxygen and redox potential environment favoring growth and persistence of anaerobic microbial populations, including Clostridium botulinum, the causal agent of botulism in humans, birds, and other wildlife. In addition to the diverse population of microbes, a dynamic chemical environment is generated, which involves production of numerous organic and inorganic substances, many of which are believed to be toxic to the sand and aquatic biotic communities. In this study, we used 16S-rDNA-based-amplicon sequencing and microfluidic-based quantitative PCR approaches to characterize the bacterial community structure and the abundances of human pathogens associated with Cladophora at different stages (up to 90days) of algal decay in laboratory microcosms. Oxygen levels were largely depleted after a few hours of incubation. As Cladophora decayed, the algal microbial biodiversity decreased within 24h, and the mat transitioned from an aerobic to anaerobic environment. There were increasing abundances of enteric and pathogenic bacteria during decomposition of Cladophora, including Acinetobacter, Enterobacter, Kluyvera, Cedecea, and others. In contrast, there were no or very few sequences (<0.07%) assigned to such groups in fresh Cladophora samples. Principal coordinate analysis indicated that the bacterial community structure was dynamic and changed significantly with decay time. Knowledge of microbial communities and chemical composition of decaying algal mats is critical to our further understanding of the role that Cladophora plays in a beach ecosystem's structure and function, including the algal role in trophic interactions. Based on these findings, public and environmental health concerns should be considered when decaying Cladophora mats accumulate Great Lakes shorelines. PMID- 27665448 TI - Endophytic fungi and soil microbial community characteristics over different years of phytoremediation in a copper tailings dam of Shanxi, China. AB - We conducted a survey of native grass species infected by endophytic fungi in a copper tailings dam over progressive years of phytoremediation. We investigated how endophytic fungi, soil microbial community structure and soil physiochemical properties and enzymatic activity varied in responses to heavy metal pollution over different stages of phytoremediation. endophyte infection frequency increased with years of phytoremediation. Rates of endophyte infection varied among different natural grass species in each sub-dam. Soil carbon content and soil enzymatic activity gradually increased through the years of phytoremediation. endophyte infection rates of Bothriochloa ischaemum and Festuca rubra were positively related to levels of cadmium (Cd) pollution levels, and fungal endophytes associated with Imperata cylindrical and Elymus dahuricus developed tolerance to lead (Pb). The structure and relative abundance of bacterial communities varied little over years of phytoremediation, but there was a pronounced variation in soil fungi types. Leotiomycetes were the dominant class of resident fungi during the initial phytoremediation period, but Pezizomycetes gradually became dominant as the phytoremediation period progressed. Fungal endophytes in native grasses as well as soil fungi and soil bacteria play different ecological roles during phytoremediation processes. PMID- 27665450 TI - On the relation between fluvio-deltaic flood basin geomorphology and the wide spread occurrence of arsenic pollution in shallow aquifers. AB - Pollution of groundwater with natural (geogenic) arsenic occurs on an enormous, world-wide scale, and causes wide-spread, serious health risks for an estimated more than hundred million people who depend on the use of shallow aquifers for drinking and irrigation water. A literature review of key studies on arsenic concentration levels yields that Holocene fluvial and deltaic flood basins are the hotspots of arsenic pollution, and that the dominant geomorphological setting of the arsenic-polluted areas consists of shallow-depth meandering-river deposits with sand-prone fluvial point-bar deposits surrounded by clay-filled (clay plug) abandoned meander bends (oxbow lakes). Analysis of the lithofacies distribution and related permeability contrasts of the geomorphological elements in two cored wells in a point bar and adjacent clay plug along the Ganges River, in combination with data of arsenic concentrations and organic matter content reveals that the low-permeable clay-plug deposits have a high organic matter content and the adjacent permeable point-bar sands show high but spatially very variable arsenic concentrations. On the basis of the geomorphological juxtaposition, the analysis of fluvial depositional processes and lithofacies characteristics, inherent permeability distribution and the omnipresence of the two geomorphological elements in Holocene flood basins around the world, a generic model is presented for the wide-spread arsenic occurrence. The anoxic deeper part (hypolimnion) of the oxbow lake, and the clay plugs are identified as the loci of reactive organic carbon and microbial respiration in an anoxic environment that triggers the reductive dissolution of iron oxy-hydroxides and the release of arsenic on the scale of entire fluvial floodplains and deltaic basins. The adjacent permeable point-bar sands are identified as the effective trap for the dissolved arsenic, and the internal permeability heterogeneity is the cause for aquifer compartmentalization, with large arsenic concentration differences between neighboring compartments. PMID- 27665449 TI - Water-soluble elements in snow and ice on Mt. Yulong. AB - Melting of high-elevation glaciers can be accelerated by the deposition of light absorbing aerosols (e.g., organic carbon, mineral dust), resulting in significant reductions of the surface albedo on glaciers. Organic carbon deposited in glaciers is of great significance to global carbon cycles, snow photochemistry, and air-snow exchange processes. In this work, various snow and ice samples were collected at high elevation sites (4300-4850masl) from Mt. Yulong on the southeastern Tibetan Plateau in 2015. These samples were analyzed for water soluble organic carbon (DOC), total nitrogen (TN), and water-soluble inorganic ions (WSIs) to elucidate the chemical species and compositions of the glaciers in the Mt. Yulong region. Generally, glacial meltwater had the lowest DOC content (0.39mgL-1), while fresh snow had the highest (2.03mgL-1) among various types of snow and ice samples. There were obvious spatial and temporal trends of DOC and WSIs in glaciers. The DOC and TN concentrations decreased in the order of fresh snow, snow meltwater, snowpit, and surface snow, resulting from the photolysis of DOC and snow's quick-melt effects. The surface snow had low DOC and TN depletion ratios in the melt season; specifically, the ratios were -0.79 and -0.19mgL-1d-1, respectively. In the winter season, the ratios of DOC and TN were remarkably higher, with values of -0.20mgL-1d-1 and -0.08mgL-1d-1, respectively. A reduction of the DOC and TN content in glaciers was due to snow's quick melt and sublimation. Deposition of these light-absorbing impurities (LAPs) in glaciers might accelerate snowmelt and even glacial retreat. PMID- 27665451 TI - The Tropical Ecology, Assessment and Monitoring (TEAM) Network: An early warning system for tropical rain forests. AB - While there are well established early warning systems for a number of natural phenomena (e.g. earthquakes, catastrophic fires, tsunamis), we do not have an early warning system for biodiversity. Yet, we are losing species at an unprecedented rate, and this especially occurs in tropical rainforests, the biologically richest but most eroded biome on earth. Unfortunately, there is a chronic gap in standardized and pan-tropical data in tropical forests, affecting our capacity to monitor changes and anticipate future scenarios. The Tropical Ecology, Assessment and Monitoring (TEAM) Network was established to contribute addressing this issue, as it generates real time data to monitor long-term trends in tropical biodiversity and guide conservation practice. We present the Network and focus primarily on the Terrestrial Vertebrates protocol, that uses systematic camera trapping to detect forest mammals and birds, and secondarily on the Zone of Interaction protocol, that measures changes in the anthroposphere around the core monitoring area. With over 3 million images so far recorded, and managed using advanced information technology, TEAM has created the most important data set on tropical forest mammals globally. We provide examples of site-specific and global analyses that, combined with data on anthropogenic disturbance collected in the larger ecosystem where monitoring sites are, allowed us to understand the drivers of changes of target species and communities in space and time. We discuss the potential of this system as a candidate model towards setting up an early warning system that can effectively anticipate changes in coupled human natural system, trigger management actions, and hence decrease the gap between research and management responses. In turn, TEAM produces robust biodiversity indicators that meet the requirements set by global policies such as the Aichi Biodiversity Targets. Standardization in data collection and public sharing of data in near real time are essential features of such system. PMID- 27665452 TI - The role of land use changes in the distribution of shallow landslides. AB - The role of land use dynamics on shallow landslide susceptibility remains an unresolved problem. Thus, this work aims to assess the influence of land use changes on shallow landslide susceptibility. Three shallow landslide-prone areas that are representative of peculiar land use settings in the Oltrepo Pavese (North Apennines) are analysed: the Rio Frate, Versa and Alta Val Tidone catchments. These areas were affected by widespread land abandonment and modifications in agricultural practices from 1954 to 2012 and relevant shallow landslide phenomena in 2009, 2013 and 2014. A multi-temporal land use change analysis allows us to evaluate the degree of transformation in the three investigated areas and the influence of these changes on the susceptibility to shallow landslides. The results show that the three catchments were characterised by pronounced land abandonment and important changes in agricultural practices. In particular, abandoned cultivated lands that gradually recovered through natural grasses, shrubs and woods were identified as the land use change classes that were most prone to shallow landslides. Additionally, the negative qualities of the agricultural maintenance practices increased the surface water runoff and consequently intensified erosion processes and instability phenomena. Although the land use was identified as the most important predisposing factor in all the study areas, some cases existed in which the predisposition of certain areas to shallow landslides was influenced by the combined effect of land use changes and the geological conditions, as highlighted by the high susceptibility of slopes that are characterised by adverse local geological (thick soils derived from clayey-marly bedrocks) and geomorphological (slope angle higher than 25 degrees ) conditions. Thus, the achieved results are particularly useful to understand the best land conservation strategies to be adopted to reduce instability phenomena and the consequent economic losses in areas that are strongly linked to agricultural land use in these territories. PMID- 27665453 TI - Few effects of invasive plants Reynoutria japonica, Rudbeckia laciniata and Solidago gigantea on soil physical and chemical properties. AB - Biological invasions are an important problem of human-induced changes at a global scale. Invasive plants can modify soil nutrient pools and element cycling, creating feedbacks that potentially stabilize current or accelerate further invasion, and prevent re-establishment of native species. The aim of this study was to compare the effects of Reynoutria japonica, Rudbeckia laciniata and Solidago gigantea, invading non-forest areas located within or outside river valleys, on soil physical and chemical parameters, including soil moisture, element concentrations, organic matter content and pH. Additionally, invasion effects on plant species number and total plant cover were assessed. The concentrations of elements in shoots and roots of invasive and native plants were also measured. Split-plot ANOVA revealed that the invasions significantly reduced plant species number, but did not affect most soil physical and chemical properties. The invasions decreased total P concentration and increased N-NO3 concentration in soil in comparison to native vegetation, though the latter only in the case of R. japonica. The influence of invasion on soil properties did not depend on location (within- or outside valleys). The lack of invasion effects on most soil properties does not necessarily imply the lack of influence of invasive plants, but may suggest that the direction of the changes varies among replicate sites and there are no general patterns of invasion-induced alterations for these parameters. Tissue element concentrations, with the exception of Mg, did not differ between invasive and native plants, and were not related to soil element concentrations. PMID- 27665454 TI - NDVI indicated long-term interannual changes in vegetation activities and their responses to climatic and anthropogenic factors in the Three Gorges Reservoir Region, China. AB - Natural and social environmental changes in the China's Three Gorges Reservoir Region (TGRR) have received worldwide attention. Identifying interannual changes in vegetation activities in the TGRR is an important task for assessing the impact these changes have on the local ecosystem. We used long-term (1982-2011) satellite-derived Normalized Difference Vegetation Index (NDVI) datasets and climatic and anthropogenic factors to analyze the spatiotemporal patterns of vegetation activities in the TGRR, as well as their links to changes in temperature (TEM), precipitation (PRE), downward radiation (RAD), and anthropogenic activities. At the whole TGRR regional scale, a statistically significant overall uptrend in NDVI variations was observed in 1982-2011. More specifically, there were two distinct periods with different trends split by a breakpoint in 1991: NDVI first sharply increased prior to 1991, and then showed a relatively weak rate of increase after 1991. At the pixel scale, most parts of the TGRR experienced increasing NDVI before the 1990s but different trend change types after the 1990s: trends were positive in forests in the northeastern parts, but negative in farmland in southwest parts of the TGRR. The TEM warming trend was the main climate-related driver of uptrending NDVI variations pre-1990s, and decreasing PRE was the main climate factor (42%) influencing the mid-western farmland areas' NDVI variations post-1990s. We also found that anthropogenic factors such as population density, man-made ecological restoration, and urbanization have notable impacts on the TGRR's NDVI variations. For example, large overall trend slopes in NDVI were more likely to appear in TGRR regions with large fractions of ecological restoration within the last two decades. The findings of this study may help to build a better understanding of the mechanics of NDVI variations in the periods before and during TGDP construction for ongoing ecosystem monitoring and assessment in the post-TGDP period. PMID- 27665455 TI - Roseovarius lacus sp. nov., isolated from Yuncheng Saline Lake, China. AB - Strain GSS12T, a Gram-negative, aerobic, non-flagellated, ovoid- to rod-shaped (0.5-0.7 * 0.9-3.0 um) bacterium, was isolated from Yuncheng Saline Lake, China. Growth occurred with 0.5-16.0 % (w/v) NaCl (optimum 4.5 %), at pH 5.0-10.0 (optimum pH 6.0-6.5) and at 10-50 degrees C (optimum 37 degrees C). The major fatty acids (>5.0 %) found in GSS12T were summed feature 8 (72.2 %), C16:0 (9.0 %) and C18:1 omega7c 11-methyl (6.4 %). The DNA G+C content was 62.7 mol%. Analysis of the 16S rRNA gene sequences showed that strain GSS12T forms a stable clade with species of the genus Roseovarius, being related to R. pacificus 81-2T and R. litoreus GSW-M15T with 97.9 and 96.7 % of sequence similarity, respectively. The DNA-DNA relatedness values between strain GSS12T and R. pacificus 81-2T and R. halotolerans HJ50T were low (36 and 29 %, respectively). The phenotypic, physiological, biochemical and genetic characteristics support the assignment of strain GSS12T to the genus Roseovarius and represent a novel species. The name Roseovarius lacus sp. nov. is proposed, with strain GSS12T (=KCTC 52185T =MCCC 1K02302T) as the type strain. PMID- 27665456 TI - Genomic and transcriptome analysis of triclosan response of a multidrug-resistant Acinetobacter baumannii strain, MDR-ZJ06. AB - During the last decade, an increasing amount of attention has focused on the potential threat of triclosan to both the human body and environmental ecology. However, the role of triclosan in the development of drug resistance and cross resistance is still in dispute ascribed to largely unknown of triclosan resistance mechanism. In this work, Acinetobacter baumannii MDR-ZJ06, a multidrug resistant strain, was induced by triclosan, and the genomic variation and transcriptional levels were investigated, respectively. The comparative transcriptomic analysis found that several general protective mechanisms were enhanced under the triclosan condition, including responses to reactive oxygen species and cell membrane damage. Meanwhile, all of the detected fifteen single nucleotide polymorphisms were not directly associated triclosan tolerance. In summary, this work revealed the crucial role of the general stress response in A. baumannii under a triclosan stress condition, which informs a more comprehensive understanding of the role of triclosan in the spread of drug-resistant bacteria. PMID- 27665457 TI - Novel clinical and therapeutic aspects in autoimmunity. PMID- 27665458 TI - ASIA syndrome, calcinosis cutis and chronic kidney disease following silicone injections. A case-based review. AB - An immunologic adjuvant is a substance that enhances the antigen-specific immune response preferably without triggering one on its own. Silicone, a synthetic polymer used for reconstructive and cosmetic purposes, can cause, once injected, local and/or systemic reactions and trigger manifestations of autoimmunity, occasionally leading to an overt autoimmune disease. Siliconosis, calcinosis cutis with hypercalcemia and chronic kidney disease have all been reported in association with silicone injection. Here, we describe a case of autoimmune/auto inflammatory syndrome induced by adjuvants, calcinosis cutis and chronic kidney disease after liquid silicone multiple injections in a young man who underwent a sex reassignment surgery, followed by a review of the literature. To our knowledge, this is the first report describing the concomitance of the three clinical conditions in the same patients. The link between silicone and the immune system is not completely understood yet and requires further reports and investigations with long-term data, in order to identify the main individual and genetical risk factors predisposing to the wide spectrum of the adjuvant-induced responses. PMID- 27665460 TI - Effect of continuous positive airway pressure (CPAP) therapy on IL-23 in patients with obstructive sleep apnea. AB - Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder characterized by repeated episodes of apnea and hypopnea during sleep. Continuous positive airway pressure (CPAP) is the most effective method for treating OSAS and alleviating the patients' symptoms. The aim of this study was to assess the effect of 3-month CPAP therapy on serum levels of IL-23 in patients with OSAS. Twenty-three patients with newly diagnosed moderate-to-severe OSAS who had not yet started nasal CPAP treatment were prospectively enrolled. All of the subjects underwent simple spirometry and an overnight sleep study. Twenty-seven healthy individuals without OSAS were also recruited as the control group. Serum IL-23 and C-reactive protein (CRP) levels were measured before and after 3 months of CPAP therapy. There was no significant difference between moderate and severe OSAS patients in IL-23 and CRP, but both parameters were significantly higher than control group. The CPAP treatment produced a significant decrease in the levels of the inflammatory mediators CRP and IL-23 in patients. Changes in IL-23 were positively correlated with changes in AHI and in CRP. In conclusion, based on these results, serum IL-23 levels reflect OSAS-related systemic inflammation and are a useful marker for improvement in OSAS following CPAP therapy. PMID- 27665459 TI - The role of adenosinergic pathway in human autoimmune diseases. AB - Autoimmune diseases are characterized by the abnormal immune response against self-tissue, which are caused by the failure of nature immune homeostasis. Nature immune homeostasis represents the normal state of appropriate immune response to nonself-antigen and unresponsiveness to self-antigens. In normal situation, immune homeostasis is regulated by immunosuppressive signal and immunostimulating signal together. Accumulating data have demonstrated that the adenosinergic pathway played key roles in immune suppression and shield body from an excessive inflammatory response. The deficiency of adenosinergic pathway results in the imbalance between the pro- and anti-inflammatory activities. Thus, researchers pay much attention to the role of adenosinergic pathway in autoimmune diseases development. To date, accumulating data have suggested an important role of adenosinergic pathway-related molecules (i.e., CD39, CD73, ADA, adenosine receptors, etc.) in many types of human autoimmune diseases. More importantly, these findings have presented potential value of adenosinergic pathway analysis to be used for autoimmune diseases diagnosis, monitoring and treatment. In this review, we will provide a comprehensive description of the role of adenosinergic pathway in human autoimmune diseases. PMID- 27665461 TI - Characteristics of polycyclic aromatic hydrocarbons in food oils in Beijing catering services. AB - The concentrations and characteristics of 16 polycyclic aromatic hydrocarbons (PAHs) in 48 oil samples randomly collected from 30 catering services that employ six cooking methods were quantified via high-performance liquid chromatography (HPLC). These 16 PAHs were detected in almost all of the samples. The levels of Sigma16PAHs, Sigma4PAHs, benzo[a]pyrene (BaP), and total BaP equivalents (SigmaBaPeq) for the six cooking methods exceeded the legal limit. The concentrations of Sigma4PAHs were approximately 9.5 to 16.4 times the legal limit proposed by the European Commission (Off J Eur Union 215:4-8, 2011), and the level of BaP exceeded the national standard in China by 4.7- to 10.6-fold, particularly in oil from fried foods. Low molecular weight PAHs (LMW PAHs) were predominant in fried food oil from different catering services and accounted for 94.8 % of these oils, and the SigmaBaPeq of the high molecular weight PAHs (HMW PAHs) was 11.5-fold higher than that of the LMW PAHs. The concentrations of Sigma16PAHs (3751.9-7585.8 MUg/kg), Sigma4PAHs (144.6-195.7 MUg/kg), BaP (79.7 135.8 MUg/kg), and SigmaBaPeq (231.0-265.4 MUg/kg) were highest in the samples from fast food restaurants/buffets (FB), followed by those from fried food stalls (FS) and then cooking restaurants/cafeterias (RC). The results of this study suggest that the government should strengthen control and supervision of PAH contamination in food and edible oils. PMID- 27665462 TI - Levels of arsenic, mercury, cadmium, copper, lead, zinc, and manganese in serum and whole blood of resident adults from mining and non-mining communities in Ghana. PMID- 27665463 TI - Production and characterization of bio-oil from the pyrolysis of waste frying oil. AB - In this present work, the disposal of waste frying oil was explored. The experiment tests were performed under nitrogen (N2) atmosphere at 5 degrees C/min heating rate from the ambient temperature to 500 degrees C. In these operating conditions, the obtained pyrolitic liquid fraction was 76 wt% formed by 63.87 wt% of crude bio-oil and 12.13 wt% of aqueous fraction. The chemical characterization using FTIR, GC, and GC/MS has revealed that the bio-oil is a complex chemical mixture of linear saturated, unsaturated, and cyclic hydrocarbons and oxygenated compounds such as carboxylic acids, ketones, aldehydes, and alcohols. Moreover, the produced bio-oil can be considered as promising fuel with high calorific value (~39 MJ/kg). However, the higher acidity (~125 mg KOH/g sample) and viscosity (9.53 cSt at 40 degrees C) limit currently its direct use in engines. Therefore, although several promising results, further investigations are requested to improve the bio-oil quality in order to find an environmentally friendly issue to waste frying oil. PMID- 27665465 TI - Theoretical study of penta- and heteropentadienyl beryllium complexes coordinated to hydrogen molecules. AB - A series of penta- and heteropentadienyl [CH2CHCHCHXBe]+, (X = CH2, O, NH, S) complexes has been theoretically studied. All calculated complexes show beryllium atoms with two, three, and five coordination numbers. The density functional theory (DFT) was used to determine the electron and structural behavior of those beryllium complexes. The nature of the ligands plays an important role in the form of binding to the beryllium atom. Beryllium structures 1-4 are able to coordinate only one hydrogen molecule. A molecular orbital analysis for all complexes was performed in order to know more about the nature of their bonding scheme. PMID- 27665466 TI - Predicting protein subcellular localization based on information content of gene ontology terms. AB - Predicting the location where a protein resides within a cell is important in cell biology. Computational approaches to this issue have attracted more and more attentions from the community of biomedicine. Among the protein features used to predict the subcellular localization of proteins, the feature derived from Gene Ontology (GO) has been shown to be superior to others. However, most of the sights in this field are set on the presence or absence of some predefined GO terms. We proposed a method to derive information from the intrinsic structure of the GO graph. The feature vector was constructed with each element in it representing the information content of the GO term annotating to a protein investigated, and the support vector machines was used as classifier to test our extracted features. Evaluation experiments were conducted on three protein datasets and the results show that our method can enhance eukaryotic and human subcellular location prediction accuracy by up to 1.1% better than previous studies that also used GO-based features. Especially in the scenario where the cellular component annotation is absent, our method can achieved satisfied results with an overall accuracy of more than 87%. PMID- 27665464 TI - In silico structural characterization of protein targets for drug development against Trypanosoma cruzi. AB - Trypanosoma cruzi is the protozoan pathogen responsible for Chagas disease, which is a major public health problem in tropical and subtropical regions of developing countries and particularly in Brazil. Despite many studies, there is no efficient treatment against Chagas disease, and the search for new therapeutic targets specific to T. cruzi is critical for drug development. Here, we have revisited 41 protein sequences proposed by the analogous enzyme pipeline, and found that it is possible to provide structures for T. cruzi sequences with clear homologs or analogs in H. sapiens and likely associated with trypanothione reductase, cysteine synthase, and ATPase functions, and structures for sequences specific to T. cruzi and absent in H. sapiens associated with 2,4-dienoyl-CoA reductase, and leishmanolysin activities. The implications of our structures refined by atomistic molecular dynamics (monomer or dimer states) in their in vitro environments (aqueous solution or membrane bilayers) are discussed for drug development and suggest that all protein targets, except cysteine synthase, merit further investigation. PMID- 27665467 TI - Variability of the multifocal electroretinogram based on the type and position of the electrode. AB - PURPOSE: To evaluate and compare the wave amplitude of multifocal electroretinogram (mfERG) measurements and discomfort from Dawson-Trick-Litzkow (DTL) electrode located on the cornea (cDTL) and on the conjunctival fornix (fDTL) and ERG-jet contact lens electrode (CL). METHODS: Thirty-six patients and 18 healthy volunteers were evaluated with three different methods (cDTL, fDTL and CL). Wave amplitude, number of artifacts, number of electrode dislocations and level of discomfort obtained with each electrode were compared. These variables were also compared between patients and healthy volunteers (control group). Comparisons between wave amplitudes were made using intraclass correlation coefficient (ICC). RESULTS: Responses by the three tested electrode were better correlated (ICC) in patient (0.616-0.756) than in control groups (0.342-0.679). CL provided the highest wave amplitude in both groups (p < 0.005), but it was associated with higher discomfort (p < 0.001) and the highest rate of dislocations (72 and 100 % in control and patients, respectively). Looking at the differences obtained by each electrode between both groups, CL seems to be able to differentiate patient from control in the ring 1 of the mfERG. By contrast, fDTL gave the lowest wave amplitude in both groups, but it had the advantage to, apparently, discriminate between patients and control group in rings 1 and 2. cDTL produced more artifacts than the other electrodes in both groups (p < 0.001). CONCLUSIONS: Although wave amplitude measurements with different electrodes were correlated, they cannot be directly compared, so it is mandatory to create an appropriate normative database with each electrode. Despite providing the lowest amplitudes, fDTL seems to offer the best features to perform mfERG regarding discomfort, number of artifacts and diagnostic capability. PMID- 27665469 TI - Survival Benefit and Safety of Bevacizumab in Combination with Erlotinib as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: A Meta Analysis. AB - BACKGROUND: Recently, the need for maintenance chemotherapy arose as a result of the significantly improved survival of patients with metastatic colorectal cancer (mCRC) without increasing adverse events. Currently used maintenance regimens are fluoropyrimidines, bevacizumab, and the combination of fluoropyrimidine with bevacizumab. A new combination with bevacizumab and erlotinib, a tyrosine kinase inhibitor of the epithelial growth factor receptor, has shown synergistic effects in preclinical tests and promising results in some clinical trials. Whether bevacizumab combined with erlotinib vs. bevacizumab alone as maintenance therapy will further improve the clinical outcomes in patients with mCRC is controversial. We conducted this meta-analysis to compare the survival benefit and safety of these two regimens in patients with mCRC. METHODS: We searched PubMed, EMBASE, and the Central Registry of Controlled Trials of the Cochrane Library up to August 2016. We also searched the Proceedings of the American Society of Clinical Oncology (1986 to August 2016). Abstracts were manually searched to identify relevant trials. A total of three randomized controlled trials with 682 patients met the inclusion criteria. RESULTS: Our results demonstrated that bevacizumab combined with erlotinib significantly improved overall survival (hazard ratio 0.78; 95 % confidence interval 0.66-0.93; p = 0.006) and progression-free survival (hazard ratio 0.79; 95 % confidence interval 0.68-0.92; p = 0.002). Significantly more grade 3 rash, diarrhea, infection total, and fatigue were observed in the bevacizumab combined with erlotinib arm, which were controllable and reversible. CONCLUSIONS: Based on current evidence, the addition of erlotinib to bevacizumab as maintenance therapy significantly increases overall survival and progression-free survival with an increased but manageable toxicity in patients with mCRC. It should be considered as a treatment option for these patients under the premise of a reasonable selection of the target population. PMID- 27665468 TI - Mitochondrial Ca2+ uptake pathways. AB - Calcium (Ca2+) plays diverse roles in all living organisms ranging from bacteria to humans. It is a structural element for bones, an essential mediator of excitation-contraction coupling, and a universal second messenger in the regulation of ion channel, enzyme and gene expression activities. In mitochondria, Ca2+ is crucial for the control of energy production and cellular responses to metabolic stress. Ca2+ uptake by the mitochondria occurs by the uniporter mechanism. The Mitochondrial Ca2+ Uniporter (MCU) protein has recently been identified as a core component responsible for mitochondrial Ca2+ uptake. MCU knockout (MCU KO) studies have identified a number of important roles played by this high capacity uptake pathway. Interestingly, this work has also shown that MCU-mediated Ca2+ uptake is not essential for vital cell functions such as muscle contraction, energy metabolism and neurotransmission. Although mitochondrial Ca2+ uptake was markedly reduced, MCU KO mitochondria still contained low but detectable levels of Ca2+. In view of the fundamental importance of Ca2+ for basic cell signalling, this finding suggests the existence of other currently unrecognized pathways for Ca2+ entry. We review the experimental evidence for the existence of alternative Ca2+ influx mechanisms and propose how these mechanisms may play an integral role in mitochondrial Ca2+ signalling. PMID- 27665470 TI - Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors. AB - INTRODUCTION: The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown. OBJECTIVE: The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib400/best supportive care [BSC]); S2 (imatinib400/imatinib800/BSC); S3 (imatinib400/sunitinib/BSC); and S4 (imatinib400/imatinib800/sunitinib/BSC). METHODS: A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed. RESULTS: The least costly and effective strategy was S1, at a cost of ?65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost effectiveness ratio (ICER) of ?48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of ?363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies. CONCLUSION: Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs. PMID- 27665471 TI - The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells. AB - Prostate cancer (PC) is one of the most common cancers among men. Progression of prostate cancer is associated with an increase in cellular level of interleukin-6 (IL-6). Gallic acid (GA) is a polyhydroxy phenolic compound which can inhibit the growth of cancer cells. The aim of this study was to evaluate the effects of GA treatment on cell viability, proliferation, invasion, IL-6 gene expression, IL-6 secretion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins in human prostate cancer PC3 cells. PC3 cells viability after treatment with GA (0 120MUM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of IL-6 was investigated using real-time polymerase chain reaction. Cellular concentration of pSTAT3, pERK1/2, and pAKT signaling proteins were determined by Western blotting technic. PC3 cells invasion was assessed by invasion assay test. Treatment with GA caused a significant decrease in cell viability, proliferation, invasion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins after 48h in a dose-dependent manner. The level of IL-6 and its gene expression decreased significantly in PC3 cells treated with GA. Our results show that IL-6 down-regulation and decreased IL-6 protein level in PC3 cells by GA resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins which lead to the reduction of the cell survival, proliferation, and invasion in PC3 cells. Therefore, it seems that GA can be considered an anticancer agent in the treatment of prostate cancer. PMID- 27665472 TI - Fyn-related kinase expression predicts favorable prognosis in patients with cervical cancer and suppresses malignant progression by regulating migration and invasion. AB - AIM: To investigate expression pattern, clinical significance and potential roles of fyn related kinase (FRK) in cervical cancer. METHODS: Expression of FRK protein and mRNA in 100 pairs of cervical cancer and matched non-cancerous tissue samples were detected by Western blot, immunohistochemistry and quantitative PCR, respectively. Statistical analyses were performed to evaluate associations of FRK protein expression with various clinicopathologic features and patients' prognosis. The effects of FRK on cell migration and invasion were examined using in vitro migration and invasion assays, respectively. RESULTS: Weak/negative immunostaining of FRK protein was observed in 86 (86.00%) of 100 cervical cancer tissues. Low FRK expression was significantly associated with several aggressive clinicopathologic features of cervical cancer, such as higher International Federation of Gynecology and Obstetric stage (P=0.01), the presence of lymph node metastasis (P=0.01) and recurrence (P=0.02). In addition, the survival analysis showed that cervical cancer patients with low FRK expression often had shorter overall survival than those with high FRK expression. The multivariate analysis also identified FRK expression as an independent prognostic factor of cervical cancer. Functionally, the enforced expression of FRK could efficiently inhibit cell migration and invasion of cervical cancer cells, but the knockdown of FRK dramatically enhanced cell migration and invasion. CONCLUSION: Our findings suggest that loss of FRK protein may be implicated into the tumorigenesis and cell motility of human cervical cancer. More importantly, FRK expression may function as a promising prognostic marker of this malignancy, highlighting its potentials as a candidate target for gene therapy. PMID- 27665474 TI - HDAC2 promotes the migration and invasion of non-small cell lung cancer cells via upregulation of fibronectin. AB - Recent studies indicated that histone deacetylases (HDACs) can modulate the tumorigenesis and development of cancer cells. We evaluated the expression of class I HDACs in non-small cell lung cancer (NSCLC) cells and found that HDAC2 was significantly increased in NSCLC cells as compared with the normal bronchial epithelial cell line BEAS-2B. Silencing of HDAC2 by its specific siRNAs can significantly inhibit the in vitro migration and invasion of A549 and H1395 cells. While over expression of HDAC2 by transfection of pcDNA/HDAC2 plasmid can trigger the motility of NSCLC cells. Over expression of HDAC2 increased the protein and mRNA expression of firbronectin (FN), which can accelerate the metastasis of cancer cells. Similarly, knock down of HDAC2 suppressed the expression of FN. The inhibitor of NF-kappaB, while not ERK1/2 or PI3K/Akt, attenuated HDAC2 induced up regulation of FN and invasion of NSCLC cells. Furthermore, HDAC2 can markedly increase both mRNA and protein levels of p65 in NSCLC cells. Collectively, our data revealed that HDAC2 can trigger migration and invasion of NSCLC cells via up regulation FN through activation of NF-kappaB. It suggested HDAC2 might be a potential therapeutic target for the drug development of NSCLC patients. PMID- 27665475 TI - Cancer nanotheranostics: Strategies, promises and impediments. AB - Cancer has remained one of the most indomitable conundrums for scientists over centuries due to its multifarious etiology. While improved therapeutic and diagnostic approaches have commendably augmented the rate of survival of cancer patients, a holistic riddance from the ailment is still implausible. Hence, further explorations to scout for novel strategies of cancer therapy and diagnosis are necessary. Theranostics (amalgamation of therapy and diagnostics) has emerged as one of the avant-garde strategies, which provides a two-pronged advantage in cancer management. This integrative approach has found immense relevance in light of nanotechnology. Nanoparticles can be customized (loaded with a melange of therapeutic drugs and diagnostic probes) to develop theranostic properties, thereby constructing nanotheranostic agents. These nano-composites are lucrative tools for cancer cell obliteration and simultaneous monitoring of the drug action, and can also be tailored for targeted drug delivery. Nanotheranostic agents have emerged as a prudent ploy for synchronized cancer intervention and detection of the 'route and reach' of the drugs. In this review, we discuss the diversified state-of-the-art facets of theranostic nanoparticles, including various nanoparticle-based platforms as well as the plethora of reported therapeutic drugs, aptamers, markers and diagnostic molecules that have found use in the precincts of nanotheranostics. PMID- 27665473 TI - Effects of 5-Aza-2'-deoxycytidine on expression of PP1gamma in learning and memory. AB - BACKGROUND: Learning and memory is a complex process. Some reports have shown that protein kinases (PKs) and phosphatases (PPs) are important mediators in this process. And it is also well known that protein serine/threonine phosphatase 1 (PP1) and DNA methylation are critically involved in learning and memory. METHODS: In the current study, the mice and cultured cells (NG108-15) were treated with vehicle or 5-Aza-2'-deoxycytidine (5-aza-cdR), a DNA methyltransferase (DNMT) inhibitor. The ability of learning and memory of mice was detected by Morris Water Maze, while the mRNA and protein expression levels of DNMTs and PP1gamma in mice hippocampus were measured by real-time PCR and western-blot. To further clarify whether the 5-aza-cdR effects on learning and memory depend on cell proliferation/apoptosis or not, the effects of 5-aza-cdR on the cell proliferation, apoptosis, and PP1gamma transcriptional activity were analyzed by using the xCelligence system, flow cytometer and Luciferase reporter assay, respectively. RESULTS: The ability of learning and memory was increased while the expressions of DNMTs and PP1gamma were decreased in the hippocampus of mice which were injected with 5-aza-cdR. In vitro experiments showed 10MUM 5-aza cdR inhibited cell proliferation, decreased PP1gamma transcription without inducing apoptosis. CONCLUSION: Our data demonstrate that the 5-aza-cdR restrains the expression of PP1gamma which is related to learning and memory in the mice. PMID- 27665477 TI - Pharmacological effects of Vitamin C & E on Diclofenac Sodium intoxicated Rats. AB - OBJECTIVE: The aim of this study was to evaluate the probable protective effect of vitamin C and vitamin E on diclofenac-induced acute nephrotoxicity using biochemical, molecular and histopathological examination in rats following administration of diclofenac sodium (50mg/kg, I.M). METHODS: Ninety male Wister rats were allotted in six equal groups. Rats in the 1st group (control group) were injected with physiological saline, while rats in the 2nd group (C-group) were given vitamin C (100mg/kg orally via stomach tube) for 5 successive days. The 3rd group (E-group) was given vitamin E (250mg/kg orally in diet) for 5 successive days. Rats in the 4th group (D-group) were injected by diclofenac sodium (50mg/kg, I.M) for 5 successive days. The 5th group (DvC-group) was given diclofenac sodium (50mg/kg, I.M) and vitamin C (100mg/kg orally via stomach tube) for 5 successive days. Rats in the 6th group (DvE-group) were given diclofenac sodium (50mg/kg, I.M) and vitamin E (250mg/kg orally in diet) for 5 successive days. Blood samples were collected two days post treatment (1st week of experiment), 2nd and 4th week of the experiment for assessment of urea, creatinine, malondialdehyde, nitric oxide and superoxide dismutase activities. At the end of 4th week, rats were sacrificed and kidneys were excised for biochemical analyses, histopathological evaluation and determination of kidney interleukin-1beta, interleukin-18, demsin and nepherin expressions in by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The results showed that, diclofenac induced severe kidney damage as indicated by histopathological changes and increased serum oxidative stress parameters. Behavioral changes were monitored; a significant increase in uremia in intoxicated animals was also noted indicating that diclofenac sodium provoked kidney damage in rats. Application of vitamin C (DvC-group) and vitamin E (DvE-group) were found to improve the abovementioned abnormalities. CONCLUSION: The present data suggest that, vitamin C and vitamin E might play an important role in reducing oxidative stress and kidney damage induced by diclofenac sodium. PMID- 27665476 TI - Ghrelin protects against palmitic acid or lipopolysaccharide-induced hepatocyte apoptosis through inhibition of MAPKs/iNOS and restoration of Akt/eNOS pathways. AB - BACGROUND: Ghrelin has been shown to exert various biological functions. However, the effect and mechanism of ghrelin on PA- or LPS-induced liver injury remains unknown. METHODS: Normal human hepatocyte lines (LO2 and 7701) were pretreated with ghrelin (10-8M) for 30min before stimulation with lipopolysaccharide (LPS) or palmitic acid (PA). The proliferation and apoptosis of cells were detected with CCK8, Hoechst staining and flow cytometric analysis. Levels of NO of cell supernatants were examined by enzyme-linked immunosorbent assay (ELISA). The protein levels and mRNA of target genes of endothelial NOS (eNOS) and inducible NOS (iNOS) were measured by western blotting, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Bax, Bcl2, caspase 3, p-Akt, p-P38 and p-JNK were detected by western blotting. RESULTS: Results of CCK8, Hoechst staining and flow cytometric analysis showed that ghrelin-pretreatment attenuated LPS- or PA- induced cellular proliferation inhibition and apoptosis induction. ELISA results revealed that ghrelin pretreatment reduced levels of NO of cell supernatants (P<0.05). Results of western blotting and immunofluorescence showed that protein levels of iNOS in ghrelin- pretreated group were significantly reduced compared with LPS- or PA- treated group, while protein levels of eNOS were restored by ghrelin pretreatment. Results of qRT-PCR showed that mRNA levels of Bax, iNOS were reduced by ghrelin pretreatment, while levels of mRNA of Bcl2 and eNOS were increased (P<0.05). The protein levels of pAkt were significantly increased by ghrelin pretreatment, while the protein levels of p-JNK, p-P38 and caspase 3 were reduced. The restoration of eNOS could be reversed by an Akt inhibitor. CONCLUSIONS: Ghrelin pretreatment attenuated LPS- or PA-induced hepatocyte apoptosis, which may least partly via inhibition of mitogen-activated protein kinases (MAPKs)/iNOS and restoration of Akt/eNOS pathways. PMID- 27665479 TI - The Quality of Staging Non-Small Cell Lung Cancer in the Netherlands: Data From the Dutch Lung Surgery Audit. AB - BACKGROUND: Clinical staging of non-small cell lung cancer (NSCLC) determines the initial treatment offered to a patient. The similarity between clinical and pathologic staging in some studies is as low as 50%, and others publish results as high as 91%. The Dutch Lung Surgery Audit is a clinical database that registers the clinical and pathologic TNM of almost all NSCLC patients who undergo operations in the Netherlands. The objective of this study was to determine the accuracy of clinical staging of NSCLC. METHODS: Prospective data were derived from the Dutch Lung Surgery Audit in 2013 and 2014. Patients were included if they had undergone a surgical resection for stage IA to IIIB NSCLC without neoadjuvant treatment and had a positron emission tomography-computed tomography scan as part of the clinical workup. Clinical (c)TNM and pathologic (p)TNM were compared, and whether discrepancy was based on tumor or nodal staging was determined. RESULTS: From 2,834 patients identified, 2,336 (82.4%) fulfilled the inclusion criteria and had complete data. Of these 2,336, 1,276 (54.6%) were staged accurately, 707 (30.3%) were clinically understaged, and 353 (15.1%) were clinically overstaged. In the understaged group, 346 patients had a higher pN stage (14.8%), of which 148 patients had unforeseen N2 disease (6.3%). In the overstaged group, 133 patients had a cN that was higher than the pN (5.7%). CONCLUSIONS: Accuracy of NSCLC staging in the Netherlands is low (54.6%), even in the era of positron emission tomography-computed tomography. Especially accurate nodal staging remains challenging. Future efforts should include the identification of specific pitfalls in NSCLC staging. PMID- 27665478 TI - Protective and curative effects of Bacillus subtilis SPB1 biosurfactant on high fat-high-fructose diet induced hyperlipidemia, hypertriglyceridemia and deterioration of liver function in rats. AB - This study was aimed to assess the plausible anti-obesity effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant on high fat high fructose diet-fed rats (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet (CD), HFFD, HFFD supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD+Bios1, 10mg/kg/day), HFFD receiving standard drug (HFFD+Torva, 10mg/kg/day) or SPB1 biosurfactant (HFFD+Bios2, 10mg/kg/day) during the last 4 weeks of the study. The results showed an increase in body weight of HFFD by ~19% as compared to controls (CD). Moreover, serum lipase activity underwent a threefold increase which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG) and LDL cholesterol (LDL-Ch) in serum of untreated HFFD, as well as a rise in the calculated atherogenic index (AI). Furthermore, liver dysfunction indices such as AST, ALT, CPK, LDH, GGT, ALP and T-Bilirubins exhibited remarkable increases in serum of HFFD as compared to controls (CD). Whereas, the administration of Bacillus subtilis SPB1 biosurfactant to HFFD improved the body weight gain and serum lipids profile and reverted back near normal the activities of lipase and liver toxicity indicators. In addition, notable protective and curative effects were reported in liver tissues. Overall, these results suggest that the lipopeptides biosynthesized by Bacillus subtilis SPB1 achieved an anti-obesity effect through the inhibition of lipid digestive and liver dysfunction enzymes. PMID- 27665480 TI - Quality Measures in Clinical Stage I Non-Small Cell Lung Cancer: Improved Performance Is Associated With Improved Survival. AB - BACKGROUND: National organizations have recommended quality measures for operations in early-stage non-small cell lung cancer (NSCLC). The outcomes of adherence to these guidelines are unknown. METHODS: Information about patients who underwent an operation for clinical stage I NSCLC was abstracted from the National Cancer Database. After reviewing current guidelines, the following quality measures were selected: anatomic resection, operation within 8 weeks of diagnosis, achievement of negative surgical margins, and sampling of 10 or more lymph nodes. Multivariate models identified variables independently associated with receiving quality measures and a Cox model created to evaluate overall survival. RESULTS: Between 2004 and 2013, 133,026 of 133,366 (99.7%), 126,598 of 133,366 (94.9%), 91,472 of 133,366 (68.6%), and 30,041 of 133,366 (22.5%) patients met one, two, three, or four measures. Income of at least $38,000/year (odds ratio [OR] 1.20, 95% CI: 1.15 to 1.24), insurance type (private insurance: OR 1.22, 95% CI: 1.09 to 1.36; Medicare: OR 1.16, 95% CI:1.04 to 1.30), centers with at least 38 cases/year (OR 1.18, 95% CI: 1.14 to 1.22), academic institutions (OR 1.31, 95% CI: 1.27 to 1.35), and clinical stage IB patients (OR 1.50, 95% CI: 1.40 to 1.60) were more likely to meet all four measures; whereas increasing age (OR 0.99, 95% CI: 0.99 to 0.99), women (OR 0.93, 95% CI: 0.91 to 0.96), non-Caucasian race (OR 0.83, 95% CI: 0.79 to 0.87), and increasing Charlson/Deyo comorbidity score (1: OR 0.90, 95% CI: 0.87 to 0.93; >=2: OR 0.82, 95% CI: 0.79 to 0.86) were associated with lower likelihood. Pathologic upstaging (hazard ratio [HR] 1.84, 95% CI: 1.78 to 1.89) and meeting all four measures (HR 0.39, 95% CI: 0.31 to 0.48) were most powerfully associated with overall survival. CONCLUSIONS: National adherence to quality measures in stage I NSCLC resection is suboptimal. Guideline compliance is strongly associated with survival, and vigorous efforts should be instituted by national societies to improve adherence. PMID- 27665481 TI - Clinical Staging of Stage I Non-Small Cell Lung Cancer in the Netherlands-Need for Improvement in an Era With Expanding Nonsurgical Treatment Options: Data From the Dutch Lung Surgery Audit. AB - BACKGROUND: The clinical stage of non-small cell lung cancer (NSCLC) determines the initial treatment, whereas the pathologic stage best determines prognosis and the need for adjuvant treatment. In an era in which stereotactic ablative radiotherapy (SABR) has become an alternative modality to surgical intervention, clinical staging is even more important, because pathologic staging is omitted in the case of SABR. The objective of this study was to determine the concordance between clinical and pathologic stage in routine clinical practice for patients with early-stage NSCLC. METHODS: Prospective data were derived from the Dutch Lung Surgery Audit (DLSA) in 2013 and 2014. Patients with clinical stage I NSCLC who underwent surgical resection and had a positron emission tomography-computed tomography (PET-CT) scan in their clinical workup were selected. Clinical and pathologic TNM (cTNM and pTNM) stages were compared. RESULTS: From a total of 1,790 patients with clinical stage I, 1,555 (87%) patients were included in this analysis. Concordance between cTNM and pTNM was 59.9%. Of the patients with clinical stage I, 22.6% were upstaged to pathologic stage II or higher. In total, 14.9% of all patients with clinical stage I had nodal metastases, and 5.5% of all patients had unforeseen N2 disease. In patients with clinical stage T2a tumors, 21.3% had nodal metastases, 14.5% being N1 and 6.7% being N2 disease. CONCLUSIONS: Concordance between clinical and pathologic stage is 59.9%. In patients with clinical stage I NSCLC, 22.6% were upstaged to pathologic stage II or higher, which is an indication for adjuvant chemotherapy. Improvement in accuracy of staging is thus needed, particularly for these patients. PMID- 27665483 TI - Artificial ascites and pneumoperitoneum to facilitate thermal ablation of liver tumors: a pictorial essay. AB - Image-guided percutaneous thermal ablation is increasingly utilized in the treatment of hepatic malignancies. Peripherally located hepatic tumors can be difficult to access or located adjacent to critical structures that can be injured. As a result, ablation of peripheral tumors may be avoided or may be performed too cautiously, leading to inadequate ablation coverage. In these cases, separating the tumor from adjacent critical structures can increase the efficacy and safety of procedures. Artificial ascites and artificial pneumoperitoneum are techniques that utilize fluid and gas, respectively, to insulate critical structures from the thermal ablation zone. Induction of artificial ascites and artificial pneumoperitoneum can enable complete ablation of otherwise inaccessible hepatic tumors, improve tumor visualization, minimize unintended thermal injury to surrounding organs, and reduce post-procedural pain. This pictorial essay illustrates and discusses the proper technique and clinical considerations for successful artificial ascites and pneumoperitoneum creation to facilitate safe peripheral hepatic tumor ablation. PMID- 27665482 TI - Diagnostic performance of 18-F-FDG-PET-CT in adrenal lesions using histopathology as reference standard. AB - PURPOSE: To determine the diagnostic performance of PET-CT in differentiating benign and malignant adrenal lesions when evaluating PET parameters individually as well as in combination with CT parameters, using histopathology as the reference standard. METHODS: 18F-FDG-PET-CT scans of patients undertaken within 6 months prior to pathologic evaluation of their adrenal lesion(s) were evaluated. PET assessments consisted individually of maximum standardized uptake value of the adrenal lesion (A-SUVmax) and its ("normalized") ratio to the liver (R SUVmax). The diagnostic performances of these two PET parameters were also assessed when combined with the Hounsfield density from the non-contrast CT component of the PET-CT (A-HU). Diagnostic performance was assessed by area under the curve (AUC) of the receiver operating characteristics. Multiple logistic regression analysis was used to evaluate the individual and combined parameters. RESULTS: The study cohort consisted of 61 adrenal lesions (59 patients). Malignant lesions (n = 52) had significantly higher median PET and CT parameters than benign lesions: A-SUVmax (11.4 vs. 6.1), R-SUVmax (3.3 vs. 1.7), and A-HU (37 vs. 24) [all p < 0.023]. AUC for the PET parameters individually was almost identical: 0.75 for A-SUVmax and 0.74 for R-SUVmax. On univariate analysis, thresholds of A-SUVmax >3.47 and R-SUVmax >0.83 yielded maximum accuracy (both 87%). The combination of these PET parameters individually with A-HU improved both AUC and accuracy (0.81% and 93%, respectively). CONCLUSIONS: The individual PET parameters A-SUVmax and R-SUVmax have similar diagnostic performance for differentiating malignant and benign adrenal lesions; their performance and accuracy improve when combined with the CT component (A-HU). PMID- 27665484 TI - The Utility of the Weight and Lifestyle Inventory (WALI) in Predicting 2-Year Weight Loss After Bariatric Surgery. AB - BACKGROUND: Emotional eating (EE) has been implicated as an important variable in bariatric surgery and is frequently assessed during preoperative evaluations. Little is known about the association between preoperative EE and postoperative outcomes. This study examined associations between preoperative EE, as measured by the Weight and Lifestyle Inventory, and 2-year postoperative percent weight loss. METHODS: Data collected during preoperative evaluations were analyzed retrospectively. A total of 685 patients completed intake data, with 357 patients (52 %) completing 2-year follow-up measures. The average time from the initial appointment to surgery is 6 months. Preoperative data was collected at approximately month 2 of this 6-month period. Follow-up data was collected during 2-year postoperative follow-up visits. RESULTS: The average percent of weight lost was 22.93 (SD = 13.62). Analyses indicated that (1) EE was not associated with percent weight loss for the overall sample, (2) EE was not associated with percent weight loss for females, (3) EE in response to positive affect was associated with percent weight loss for males, and (4) the interaction between preoperative depressive symptoms and EE was not associated with percent weight loss for either sex. CONCLUSION: While the WALI provides a fruitful means of gathering clinical information, results suggested no association between scores on Section H of the WALI and weight loss. The results suggest that EE may impact surgical outcomes differentially in men as compared to women. Future research should seek to replicate these findings and focus on gender differences related to surgical outcomes. PMID- 27665486 TI - Dynamic flux of microvesicles modulate parasite-host cell interaction of Trypanosoma cruzi in eukaryotic cells. AB - Extracellular vesicles released from pathogens may alter host cell functions. We previously demonstrated the involvement of host cell-derived microvesicles (MVs) during early interaction between Trypanosoma cruzi metacyclic trypomastigote (META) stage and THP-1 cells. Here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. First, we observed that infective host cell-derived trypomastigote (tissue culture-derived trypomastigote [TCT]), META, and noninfective epimastigote (EPI) stages were able to induce different levels of MV release from THP-1 cells; however, only META and TCT could increase host cell invasion. Fluorescence resonance energy transfer microscopy revealed that THP-1 derived MVs can fuse with parasite-derived MVs. Furthermore, MVs derived from the TCT-THP-1 interaction showed a higher fusogenic capacity than those from META- or EPI-THP-1 interaction. However, a higher presence of proteins from META (25%) than TCT (12%) or EPI (5%) was observed in MVs from parasite-THP-1 interaction, as determined by proteomics. Finally, sera from patients with chronic Chagas disease at the indeterminate or cardiac phase differentially recognized antigens in THP-1-derived MVs resulting only from interaction with infective stages. The understanding of intracellular trafficking and the effect of MVs modulating the immune system may provide important clues about Chagas disease pathophysiology. PMID- 27665485 TI - Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67. AB - OBJECTIVES: Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity. METHODS: We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files. RESULTS: Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403). CONCLUSION: In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement. PMID- 27665487 TI - Factors influencing participation in health behaviors in endometrial cancer survivors. AB - BACKGROUND: The study purpose was to investigate endometrial cancer survivors' health perceptions following cessation of active cancer treatment and to explore factors influencing participation in health-promoting behaviors. METHODS: Face-to face interviews were conducted with participants who had completed active treatment of cancer within the previous 3 years. Participants were 22 endometrial cancer survivors (mean age = 62.55 years, SD = 7.08) at risk of cardiovascular disease who were recruited from 2 oncologists in Perth, Western Australia. Interview transcripts were analyzed using thematic analysis. RESULTS: Five main themes emerged: physical activity knowledge and advice; authority of oncologists; accountability and external motivation; monitoring and barriers to healthy eating; and physical activity. Participants recalled that specific recommendations for physical activity or body weight were rarely made by the oncologists, but felt they would have followed such lifestyle advice if it had been given. The overarching theme was the need for accountability and monitoring to successfully change health behaviors. CONCLUSIONS: Interventions aimed at promoting health behaviors in endometrial cancer survivors should include referral and advice from oncologists, provision of monitoring, and promotion of planning and self-control. Implications for endometrial cancer survivors at risk of cardiovascular disease: these women are likely to benefit most from interventions aimed at promoting planning, self-regulation and problem solving and regular follow-up. PMID- 27665488 TI - Effect of Dispatcher-Assisted Cardiopulmonary Resuscitation Program and Location of Out-of-Hospital Cardiac Arrest on Survival and Neurologic Outcome. AB - STUDY OBJECTIVE: We study the effect of a nationwide dispatcher-assisted cardiopulmonary resuscitation (CPR) program on out-of-hospital cardiac arrest outcomes by arrest location (public and private settings). METHODS: All emergency medical services (EMS)-treated adults in Korea with out-of-hospital cardiac arrests of cardiac cause were enrolled between 2012 and 2013, excluding cases witnessed by EMS providers and those with unknown outcomes. Exposure was bystander CPR categorized into 3 groups: bystander CPR with dispatcher assistance, bystander CPR without dispatcher assistance, and no bystander CPR. The endpoint was good neurologic recovery at discharge. Multivariable logistic regression analysis was performed. The final model with an interaction term was evaluated to compare the effects across settings. RESULTS: A total of 37,924 patients (31.1% bystander CPR with dispatcher assistance, 14.3% bystander CPR without dispatcher assistance, and 54.6% no bystander CPR) were included in the final analysis. The total bystander CPR rate increased from 30.9% in quarter 1 (2012) to 55.7% in quarter 4 (2014). Bystander CPR with and without dispatcher assistance was more likely to result in higher survival with good neurologic recovery (4.8% and 5.2%, respectively) compared with no bystander CPR (2.1%). The adjusted odds ratios for good neurologic recovery were 1.50 (95% confidence interval [CI] 1.30 to 1.74) in bystander CPR with dispatcher assistance and 1.34 (95% CI 1.12 to 1.60) in bystander CPR without it compared with no bystander CPR. For arrests in private settings, the adjusted odds ratios were 1.58 (95% CI 1.30 to 1.92) in bystander CPR with dispatcher assistance and 1.28 (95% CI 0.98 to 1.67) in bystander CPR without it; in public settings, the adjusted odds ratios were 1.41 (95% CI 1.14 to 1.75) and 1.37 (95% CI 1.08 to 1.72), respectively. CONCLUSION: Bystander CPR regardless of dispatcher assistance was associated with improved neurologic recovery after out-of-hospital cardiac arrest. However, for out-of-hospital cardiac arrest cases in private settings, bystander CPR was associated with improved neurologic recovery only when dispatcher assistance was provided. PMID- 27665489 TI - Exercise-induced bronchoconstriction update-2016. AB - The first practice parameter on exercise-induced bronchoconstriction (EIB) was published in 2010. This updated practice parameter was prepared 5 years later. In the ensuing years, there has been increased understanding of the pathogenesis of EIB and improved diagnosis of this disorder by using objective testing. At the time of this publication, observations included the following: dry powder mannitol for inhalation as a bronchial provocation test is FDA approved however not currently available in the United States; if baseline pulmonary function test results are normal to near normal (before and after bronchodilator) in a person with suspected EIB, then further testing should be performed by using standardized exercise challenge or eucapnic voluntary hyperpnea (EVH); and the efficacy of nonpharmaceutical interventions (omega-3 fatty acids) has been challenged. The workgroup preparing this practice parameter updated contemporary practice guidelines based on a current systematic literature review. The group obtained supplementary literature and consensus expert opinions when the published literature was insufficient. A search of the medical literature on PubMed was conducted, and search terms included pathogenesis, diagnosis, differential diagnosis, and therapy (both pharmaceutical and nonpharmaceutical) of exercise-induced bronchoconstriction or exercise-induced asthma (which is no longer a preferred term); asthma; and exercise and asthma. References assessed as relevant to the topic were evaluated to search for additional relevant references. Published clinical studies were appraised by category of evidence and used to document the strength of the recommendation. The parameter was then evaluated by Joint Task Force reviewers and then by reviewers assigned by the parent organizations, as well as the general membership. Based on this process, the parameter can be characterized as an evidence- and consensus-based document. PMID- 27665491 TI - Reproductive performance of the largest captive Asian elephant (Elephas maximus) population in Sri Lanka. AB - The Pinnawela Elephant Orphanage (PEO) in Sri Lanka maintains one of the largest captive Asian elephant (Elephas maximus maximus) populations in the world, with a total of 79 animals (45 females and 34 males) at present. It was established in 1975 as an orphanage for rescued wild calves, and commenced natural breeding under controlled conditions when they reached breeding age. This study summarizes reproductive data of 65 live births from 38 years of records at PEO. The age at first calving (n=31) was 14.6+/-0.7years, and the numbers of females giving birth two, three, four and five times were 21, 8, 4 and 2, with corresponding inter birth intervals (IBI) of 4.9+/-0.3, 4.8+/-0.5, 7.9+/-1.9 and 5.7+/-0.5years, respectively. Females giving birth to males (5.7+/-2.2years) had longer IBIs compared to birthing female calves (4.7+/-1.1years). The average gestation for 18 pregnancies with known conception dates was 667+/-11days. The average birth weight was similar for male (83.1+/-4.6kg; n=14) and female (82.8+/-8.4kg; n=6) calves. Sex ratio for live births was 36 male:29 female and not different from 1:1; however, more males (10/14) were born after a second parity. Calf mortality and stillbirth rates were low: 7.6% and 4.4%, respectively. This study highlights the successful breeding program at the PEO, providing baseline reproductive data that can aid in improving breeding of other elephants managed under captive conditions. PMID- 27665490 TI - Killer cell immunoglobulin-like receptors are associated with common variable immune deficiency pathogenesis. PMID- 27665492 TI - Evidence-based nursing implementation in Mainland China: A scoping review. AB - BACKGROUND: It is crucial to identify the challenges of evidence-based nursing implementation faced by countries in transitional stage. PURPOSE: The purpose of this study was to identify the state of evidence on implementation in Chinese nursing contexts and to determine gaps that need to be pursued. METHODS: We performed a scoping review on existing literature on implementation studies conducted in nursing context in Mainland China. After systematically searching eight (four Chinese and four English) databases, we extracted and analyzed data from the included studies. RESULTS: Ninety-five articles met inclusion criteria. Publications were on the rise, with most funding from academic institutions. Most studies were quantitative, with patient outcomes as primary indicators. Eighteen studies used a theoretical framework. Frequently used strategies and barriers to evidence-based nursing implementation were mainly from the organizational level. CONCLUSIONS: This scoping review indicates an urgent requirement of Chinese evidence-based nursing resources, more funding and support from clinical managerial level, cooperation between academic and clinical institutes, and a call for more rigorous studies of implementation science under a Chinese nursing context. PMID- 27665493 TI - Scalability of an endoluminal spring for distraction enterogenesis. AB - INTRODUCTION: Techniques of distraction enterogenesis have been explored to provide increased intestinal length to treat short bowel syndrome (SBS). Self expanding, polycaprolactone (PCL) springs have been shown to lengthen bowel in small animal models. Their feasibility in larger animal models is a critical step before clinical use. METHODS: Juvenile mini-Yucatan pigs underwent jejunal isolation or blind ending Roux-en-y jejunojejunostomy with insertion of either a PCL spring or a sham PCL tube. Extrapolated from our spring characteristics in rodents, proportional increases in spring constant and size were made for porcine intestine. RESULTS: Jejunal segments with 7mm springs with k between 9 and 15N/m demonstrated significantly increased lengthening in isolated segment and Roux-en y models. Complications were noted in only two animals, both using high spring constant k>17N/m. Histologically, lengthened segments in the isolated and Roux models demonstrated significantly increased muscularis thickness and crypt depth. Restoration of lengthened, isolated segments back into continuity was technically feasible after 6weeks. CONCLUSION: Self-expanding, endoluminal PCL springs, which exert up to 0.6N force, safely achieve significant intestinal lengthening in a translatable, large-animal model. These spring characteristics may provide a scalable model for the treatment of SBS in children. PMID- 27665494 TI - Expression of Prx1 and Tcf4 is decreased in the diaphragmatic muscle connective tissue of nitrofen-induced congenital diaphragmatic hernia. AB - BACKGROUND/PURPOSE: Pleuroperitoneal folds (PPFs) are the source of the primordial diaphragm's muscle connective tissue (MCT), and developmental mutations have been shown to result in congenital diaphragmatic hernia (CDH). The protein paired-related homeobox 1 (Prx1) labels migrating PPF cells and stimulates expression of transcription factor 4 (Tcf4), a novel MCT marker that controls morphogenesis of the fetal diaphragm. We hypothesized that diaphragmatic Prx1 and Tcf4 expression is decreased in the nitrofen-induced CDH model. METHODS: Time-mated rats were exposed to either nitrofen or vehicle on gestational day 9 (D9). Fetal diaphragms were microdissected on D13, D15, and D18, and divided into control and nitrofen-exposed specimens. Gene expression levels of Prx1 and Tcf4 were analyzed by qRT-PCR. Immunofluorescence double staining for Prx1 and Tcf4 was performed to evaluate protein expression and localization. RESULTS: Relative mRNA expression of Prx1 and Tcf4 was significantly downregulated in PPFs (D13), developing diaphragms (D15) and fully muscularized diaphragms (D18) of nitrofen exposed fetuses compared to controls. Confocal laser scanning microscopy revealed markedly diminished Prx1 and Tcf4 expression in diaphragmatic MCT of nitrofen exposed fetuses on D13, D15, and D18 compared to controls. CONCLUSIONS: Decreased expression of Prx1 and Tcf4 in the fetal diaphragm may cause defects in the PPF derived MCT, leading to development of CDH in the nitrofen model. LEVEL OF EVIDENCE: Level 2c (Centre for Evidence-Based Medicine, Oxford). PMID- 27665495 TI - High mortality among children with gastroschisis after the neonatal period: A long-term follow-up study. AB - BACKGROUND: During the last decades neonatal outcomes for children born with gastroschisis have improved significantly. Survival rates >90% have been reported. Early prenatal diagnosis and increased survival enforce the need for valid data for long-term outcome in the pre- and postnatal counseling of parents with a child with gastroschisis. METHODS: Long-term follow-up on all newborns with gastroschisis at Odense University Hospital (OUH) from January 1 1997 December 31 2009. Follow-up included neonatal chart review for neonatal background factors, including whether a GORE(r)DUALMESH was used for staged closure, electronic questionnaires, interview and laboratory investigations. Cases were divided into complex and simple cases according to the definition by Molik et al. (2001). Survival status was determined by the national personal identification number registry. Because of the consistency of the registration, survival status was obtained from all children participating in the study. RESULTS: A total of 71 infants (7 complex and 64 simple) were included. Overall seven out of the 71 children (9.9%, median age: 52days (25-75% percentile 0 978days) had died at the time of follow-up. Three died during the neonatal period and four died after the neonatal period. Parenteral nutrition (PN) induced liver failure and suspected adhesive small bowel obstruction were the causes of deaths after the neonatal period. Overall mortality was high in the "complex" group compared to the simple group (3/7 (42.9%) vs 4/64 (6.3%), p = 0.04). Forty (62.5%) of the surviving children consented to participate in the follow-up. A total of 12 children had had suspected adhesive small bowel obstruction. Prevalence of small bowel obstruction was not related to the number of operations needed for neonatal closure of the defect. Staged closure was done in 5/12 (41.7%) who developed small bowel obstruction vs 11/35 (31.43%) without small bowel obstruction, p=0.518. A GORE(r)DUALMESH was used in 16 children (22.5%). Of these 2 were complex and 14 were simple cases. Prevalence of recurrent abdominal pain was 22.5% (9/40) among children with gastroschisis compared to 12% in a study on Danish school children, p=0.068. Gastrointestinal symptoms had led to hospital admission after primary discharge in significantly more children with gastroschisis 16 (40.0%) than children younger than 16years old in the general Danish population 129.419/1.081.542 (12.0%), p=0.000. Fecal calprotectin level was above the reference level (>50mg/kg) in 6/16 (37.5%) children >8years old with gastroschisis compared to 1/7 (14.3%) healthy children. (Fisher's exact=0.366). Only 8/38 (21.1%) children with gastroschisis reported to have an umbilicus. CONCLUSION: Mortality among children with gastroschisis is still significant with the highest risk among complicated cases. The majority of the deaths is potentially preventable as PN-related causes and suspected adhesive small bowel obstruction counted for five of seven deaths. Neither categorization upon method of abdominal wall closure nor categorization into simple and complex cases can predict the risk of adhesive small bowel obstruction. With improved administration of PN and timely information and attention to the risk of the small bowel obstruction there is good possibility that the associated mortality could decrease. Type of study and level of evidence: Prognosis study, level II. PMID- 27665496 TI - Formic acid hydrolysis/liquid chromatography isotope dilution mass spectrometry: An accurate method for large DNA quantification. AB - Liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) with formic acid hydrolysis was established for the accurate quantification of lambdaDNA. The over-decomposition of nucleobases in formic acid hydrolysis was restricted by optimizing the reaction temperature and the reaction time, and accurately corrected by using deoxynucleotides (dNMPs) and isotope-labeled dNMPs as the calibrator and the internal standard, respectively. The present method could quantify lambdaDNA with an expanded uncertainty of 4.6% using 10fmol of lambdaDNA. The analytical results obtained with the present method were validated by comparing with the results of phosphate-base quantification by inductively coupled plasma-mass spectrometry (ICP-MS). The results showed good agreement with each other. We conclude that the formic acid hydrolysis/LC-IDMS method can quantify lambdaDNA accurately and is promising as the primary method for the certification of DNA as reference material. PMID- 27665497 TI - A comparative study of drug listing recommendations and the decision-making process in Australia, the Netherlands, Sweden, and the UK. AB - Drug listing recommendations from health technology assessment (HTA) agencies often fail to coincide with one another. We conducted a comparative analysis of listing recommendations in Australia (PBAC), the Netherlands (CVZ), Sweden (TLV) and the UK (NICE) over time, examined interagency agreement, and explored how process-related factors-including time delay between HTA evaluations, therapeutic indication and orphan drug status, measure of health economic value, and comparator-impacted decision-making in drug coverage. Agreement was poor to moderate across HTA agency listing recommendations, yet it increased as the delay between HTA agency appraisals decreased, when orphan drugs were assessed, and when medicines deemed to provide low value (immunosuppressants, antineoplastics) were removed from the sample. International differences in drug listing recommendations seem to occur in part due to inconsistencies in how the supporting evidence informs assessment, but also to differences in how domestic priorities shape the value-based decision-making process. PMID- 27665498 TI - Anastomosis between the transverse cervical nerve and marginal mandibular nerve: how often does it occur? AB - Anastomoses in the neck between the sensory transverse cervical nerve (C2,3) and the cervical branch of the facial nerve are common, but communications with more superior branches of the facial nerve are rare. After we had identified a case where the transverse cervical nerve joined the marginal mandibular branch of the facial nerve in the submandibular triangle during a selective neck dissection, we searched for this variant in 86 neck dissections to see if it occurs more often than expected. We found it in one further patient. As this anastomosis of the nerve could easily be confused with the marginal mandibular branch itself, particularly during a more limited exposure (such as excision of a submandibular gland), our findings remind surgeons to be vigilant when dissecting in this area to minimise the risk of weakness of the lower lip postoperatively. PMID- 27665499 TI - Mindfulness practice: A promising approach to reducing the effects of clinician implicit bias on patients. AB - Like the population at large, health care providers hold implicit racial and ethnic biases that may contribute to health care disparities. Little progress has been made in identifying and implementing effective strategies to address these normal but potentially harmful unconscious cognitive processes. We propose that meditation training designed to increase healthcare providers' mindfulness skills is a promising and potentially sustainable way to address this problem. Emerging evidence suggests that mindfulness practice can reduce the provider contribution to healthcare disparities through several mechanisms including: reducing the likelihood that implicit biases will be activated in the mind, increasing providers' awareness of and ability to control responses to implicit biases once activated, increasing self-compassion and compassion toward patients, and reducing internal sources of cognitive load (e.g., stress, burnout, and compassion fatigue). Mindfulness training may also have advantages over current approaches to addressing implicit bias because it focuses on the development of skills through practice, promotes a nonjudgmental approach, can circumvent resistance some providers feel when directly confronted with evidence of racism, and constitutes a holistic approach to promoting providers' well-being. We close with suggestions for how a mindfulness approach can be practically implemented and identify potential challenges and research gaps to be addressed. PMID- 27665500 TI - Unraveling the meaning of patient engagement: A concept analysis. AB - OBJECTIVE: Patient engagement has been credited with contributing to improved outcomes and experiences of care. Patient engagement has become a widely used term, but remains a poorly understood concept in healthcare. Citations for the term have increased throughout the healthcare-related disciplines without a common definition. This study seeks to define the concept by identifying its attributes in the context of its use. METHODS: A concept analysis of the scientific literature in the health disciplines was performed using the Rogers method. RESULTS: The analysis revealed four defining attributes of patient engagement: personalization, access, commitment and therapeutic alliance. Patient engagement is defined as the desire and capability to actively choose to participate in care in a way uniquely appropriate to the individual, in cooperation with a healthcare provider or institution, for the purposes of maximizing outcomes or improving experiences of care. CONCLUSION: Patient engagement is both process and behavior and is shaped by the relationship between the patient and provider and the environment in which healthcare delivery takes place. PRACTICE IMPLICATIONS: The definition and the identified attributes serve as a heuristic in designing patient engagement strategies and as a basis for future development of the patient engagement concept in healthcare. PMID- 27665501 TI - Narcolepsy with cataplexy in patients aged over 60 years: a case-control study. AB - OBJECTIVE: Narcolepsy with cataplexy (NC) is a chronic disabling disease; however, there are insufficient data on older NC subjects. METHODS: A cross sectional evaluation on health and social status, including intensity and progression of NC symptoms, was performed on 42 NC patients (age 71.9 years +/- 7.5) and 46 age-and-sex-matched controls (age 72.2 years +/- 7.0). RESULTS: A greater proportion of patients than controls suffered from hypertension and type 2 diabetes. More controls had a history of treated depression; however, according to the Geriatric Depression Scale, more NC patients scored in the range of depression. There were no significant differences in Addenbrook Cognitive Examination scores. Average physical fitness assessed by the Short Physical Performance Battery was lower in the NC group. The frequency of meeting with family, friends, and participation in hobbies or sports did not differ between the two groups. CONCLUSIONS: Symptoms of NC were present throughout life. Comorbidities and lower physical fitness, which are known to be present in young and middle-aged NC subjects, were also present in older patients. Although NC subjects were less professionally active during their lifetime, they did not differ from controls in important social parameters in older age. PMID- 27665502 TI - Acetylation Enhances the Promoting Role of AIB1 in Breast Cancer Cell Proliferation. AB - The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator, which is overexpressed in various types of human cancers, including breast cancer. However, the molecular mechanisms regulating AIB1 function remain largely unknown. In this study, we present evidence demonstrating that AIB1 is acetylated by MOF in human breast cancer cells. Moreover, we also found that the acetylation of AIB1 enhances its function in promoting breast cancer cell proliferation. We further showed that the acetylation of AIB1 is required for its recruitment to E2F1 target genes by E2F1. More importantly, we found that the acetylation levels of AIB1 are greatly elevated in human breast cancer cells compared with that in non-cancerous cells. Collectively, our results shed light on the molecular mechanisms that regulate AIB1 function in breast cancer. PMID- 27665503 TI - Screening for DNA adducts in ovarian follicles exposed to benzo[a]pyrene and cigarette smoke condensate using liquid chromatography-tandem mass spectrometry. AB - A rapid mass spectrometric method was applied to non-targeted screening of DNA adducts in follicular cells (granulosa cells and theca cells) from isolated ovarian follicles that were exposed in-vitro to benzo[a]pyrene (B[a]P) and cigarette smoke condensate (CSC) for 13days of culture. The method employed a constant neutral loss (CNL) scan to identify chromatographic peaks associated to a neutral loss of deoxyribose moiety of DNA nucleosides. These peaks were subsequently analyzed by a product ion scan in tandem mass spectrometry to elucidate structures of DNA adducts. The identification was further confirmed through synthesis of proposed DNA adducts where possible. Three DNA adducts, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-dG (BPDE-dG), phenanthrene 1,2 quinone-dG (PheQ-dG) and B[a]P-7,8-quinone-dG (BPQ-dG) were identified in the follicular cells from isolated ovarian follicles exposed to B[a]P. Along with these three, an additional DNA adduct, 4-aminobiphenyl-dG, was identified in the follicular cells from isolated ovarian follicles exposed to CSC. The amounts of the identified DNA adducts in follicular cells increased in a dose-dependent manner for both B[a]P (0, 1.5, 5, 15 and 45ng/mL) and CSC (0, 30, 60, 90 and 130MUg/mL). The results revealed that B[a]P-related DNA adducts were the major adducts in the ovarian follicular cells exposed to CSC. The results also revealed that two oxidative biomarkers, 8-hydroxy-2-deoxy guanosine (8-OH-dG) and 8 isoprostane (8-IsoP), in both B[a]P-exposed and CSC-exposed ovarian follicles had strong correlations with the three DNA adducts, BPDE-dG, BPQ-dG and PheQ-dG. A pathway to describe formation of DNA adducts was proposed based on the DNA adducts observed. PMID- 27665504 TI - Guest Editorial: How stress changes the brain and causes a cluster of uniquely human diseases. PMID- 27665505 TI - Is fat talk more believable than self-affirming body talk? AB - Two experiments tested the extent to which the believability of women's body statements (fat talk or self-affirming) depends on their body type (thin or overweight). Experiment 1 (N=130) revealed fat talk was more believable than self affirming talk regardless of body type. Experiment 2's (N=125) results showed, as hypothesized, that overweight women's fat talk was significantly more believable than fat talk by thin women and self-affirming talk by either thin or overweight women. Consistent with Experiment 1, there was a trend in Experiment 2 toward thin women's fat talk being more believable than their self-affirming talk. Overall, fat talk generally may be perceived as more believable than self affirming body talk, and overweight women's fat talk may be perceived as most authentic. These results have implications for increasing understanding of fat talk's potential role in body dissatisfaction as well as the development of positive body image campaigns. PMID- 27665507 TI - Lack of male factor evaluation and opportunities lost. PMID- 27665506 TI - Cardio-Renal Syndrome Type 4: The Correlation Between Cardiorenal Ultrasound Parameters. AB - : Bakground/Aims: Cardiovascular diseases represent the leading causes of morbidity and mortality in patients with cronich kidney disease (CKD). The pathogenesis includes a complex, bidirectional interaction between heart and kidney termed cardiorenal syndrome type 4. The aim of study was to evaluate the association between renal and cardiovascular ultrasonographic parameters and identify early markers of cardiovascular risk. METHODS: A total of 35 patients with CKD and 25 healthy controls, were enrolled and we have evaluated inflammatory indexes, mineral metabolism, renal function, renal and cardiovascular ultrasonographic parameters. RESULTS: Tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (ePAPs) showed a statistically significant difference between CKD patients and healthy controls (p<0.001, p=0.05). Also 25 hydroxyvitaminD (25-OH-VitD), parathyroid hormone (iPTH), posphorus, serum uric acid, renal resistive index (RRI) and C-reactive protein (CRP) showed a significant difference between the two groups (p=0.002, p<0.001, p<0.001, p<0.001, p<0.001, p<0.001). Moreover the TAPSE correlated positively with estimated glomerula filtration rate (eGFR) and negatively with RRI (p=0.05, p=0.008), while ePAPs correlated negatively with eGFR and positively with RRI (p=0.029, p<0.001). CONCLUSION: CKD can contribute to the development and progression of right ventricle dysfunction with endothelial dysfunction, inflammation and mineral metabolism disorders. Accurate assessment of right ventricular function is recommended in patients with CKD. RRI and echocardiographic parameters can be an important instrument for the diagnosis, prognosis and therapeutic assessment of cardio-renal syndrome in these patients. PMID- 27665508 TI - Understanding host-pathogen interaction. PMID- 27665510 TI - Air pollution during pregnancy and lung development in the child. AB - Air pollution exposure has increased extensively in recent years and there is considerable evidence that exposure to particulate matter can lead to adverse respiratory outcomes. The health impacts of exposure to air pollution during the prenatal period is especially concerning as it can impair organogenesis and organ development, which can lead to long-term complications. Exposure to air pollution during pregnancy affects respiratory health in different ways. Lung development might be impaired by air pollution indirectly by causing lower birth weight, premature birth or disturbed development of the immune system. Exposure to air pollution during pregnancy has also been linked to decreased lung function in infancy and childhood, increased respiratory symptoms, and the development of childhood asthma. In addition, impaired lung development contributes to infant mortality. The mechanisms of how prenatal air pollution affects the lungs are not fully understood, but likely involve interplay of environmental and epigenetic effects. The current epidemiological evidence on the effect of air pollution during pregnancy on lung function and children's respiratory health is summarized in this review. While evidence for the adverse effects of prenatal air pollution on lung development and health continue to mount, rigorous actions must be taken to reduce air pollution exposure and thus long-term respiratory morbidity and mortality. PMID- 27665511 TI - Maternal HIV and Paediatric Lung Health. AB - With improved prevention of mother to child transmission of HIV, paediatric HIV disease is less common. However, the number of HIV exposed but uninfected infants is growing. Exposure to maternal HIV impacts infant respiratory health through an increase in known risk factors such as increased preterm birth and low birth weight, suboptimal breastfeeding, increased psychosocial stressors and increased exposure to infective pathogens. Exposure to the HIV virus and altered maternal immune environment result in immunologic changes in the infant that may contribute to respiratory disease risk. HIV exposed infants are at increased risk for severe pneumonia with poorer outcomes compared to unexposed infants. Maternal ART and optimal nutrition, including breastfeeding in high infective disease burden settings, reduce morbidity and mortality in HIV exposed infants and should be prioritized. The impact of exposure to maternal HIV on normal lung growth and risk for chronic respiratory disease is unknown and warrants further investigation. PMID- 27665509 TI - Prospective study of the impact of diabetes mellitus newly diagnosed by glycated hemoglobin on outcomes in patients undergoing percutaneous coronary intervention. AB - BACKGROUND: We sought to determine the prevalence of diabetes mellitus (DM) newly diagnosed by elevated glycated hemoglobin (HbA1c) in patients undergoing percutaneous coronary intervention (PCI) and its association with 1-year clinical outcomes. METHODS: We prospectively enrolled consecutive patients undergoing PCI (2011-2013). HbA1c levels were assessed during the index hospitalization and newly diagnosed DM was defined as HbA1c>=6.5% in the absence of the previous diagnosis. The primary outcome was MACCE (Major Adverse Cerebro- and Cardiovascular Events) defined as death, stroke, PCI or acute myocardial infarction at 1year. RESULTS: Diabetes was previously diagnosed in 391 (34%) patients (DM group), 221 (19%) had newly diagnosed DM based on the HbA1c level and 539 (47%) did not have diabetes (Non-DM). In DM group HbA1c was 7.80+/-1.36% as compared with 7.62+/-1.30% in patients with newly diagnosed DM (p<0.001). These patients were younger (62.0+/-11.3years) compared to DM (67.9+/-10.4years) and non-DM (63.7+/-13.0) patients, p<0.001. 1-year MACCE rates were 14.8%, 19.5% and 27.96% in the non-DM, newly diagnosed DM and DM groups, respectively (p<0.001). Multivariate analysis showed that compared to non-DM, the adjusted one year hazard ratios for MACCE were 1.75 and 1.40 in patients with known DM and newly diagnosed DM, respectively (p<0.05 for both). CONCLUSION: Newly diagnosed DM based on peri-procedural HbA1c is common and associated with increased short and long term risk for adverse outcomes. Our results may warrant routine screening for DM in all patients undergoing PCI. PMID- 27665512 TI - Diabetes in pregnancy and lung health in offspring: developmental origins of respiratory disease. AB - Diabetes is an increasingly common complication of pregnancy. In parallel with this trend, a rise in chronic lung disease in children has been observed in recent decades. While several adverse health outcomes associated with exposure to diabetes in utero have been documented in epidemiological and experimental studies, few have examined the impact of diabetes in pregnancy on offspring lung health and respiratory disease. We provide a comprehensive overview of current literature on this topic, finding suggestive evidence that exposure to diabetes in utero may have adverse effects on lung development. Delayed lung maturation and increased risk of respiratory distress syndrome have been consistently observed among infants born to mothers with diabetes and these findings are also observed in some rodent models of diabetes in pregnancy. Further research is needed to confirm and characterize epidemiologic observations that diabetes in pregnancy may predispose offspring to childhood wheezing illness and asthma. Parallel translational studies in human pregnancy cohorts and experimental models are needed to explore the role of fetal programming and other potential biological mechanisms in this context. PMID- 27665514 TI - Safety of long-acting beta2-agonists in asthma. PMID- 27665513 TI - Treatment and outcomes in necrotising autoimmune myopathy: An Australian perspective. AB - Necrotising Autoimmune Myopathy (NAM) presents as a subacute proximal myopathy with high creatine kinase levels. It is associated with statin exposure, 3 hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody, connective tissue diseases, signal recognition particle (SRP) antibody and malignancy. This case series presents our Western Australian NAM patient cohort: comparing the subgroup presentations, biopsy appearance and treatment outcomes. We retrospectively collected data on patients diagnosed with NAM at the Western Australian Neuroscience Research Institute between the years 2000 and 2015. We identified 20 patients with Necrotising Autoimmune Myopathy: 14 with anti-HMGCR antibodies; two with anti-SRP antibodies; three with connective tissue disease; two as yet unspecified. Median creatine kinase level was 6047units/L (range 1000-17000). The statin naive patients with HMGCR antibodies and patients with SRP antibodies were the most severely affected subgroups, with higher creatine kinase levels, and were more resistant to immunotherapy. Two or more immunotherapy agents were required in 90%; eight patients required IVIG and rituximab. Steroid weaning commonly precipitated relapses. Four patients had complete remission, and the remaining patients still require immunotherapy. Necrotising Autoimmune Myopathy is a potentially treatable myopathy, which can be precipitated by statin therapy and requires early, aggressive immunotherapy, usually requiring multiple steroid sparing agents for successful steroid weaning. PMID- 27665515 TI - SAVE trial: no cardiovascular benefits for CPAP in OSA. PMID- 27665516 TI - Accessing 3D microtissue metabolism: Lactate and oxygen monitoring in hepatocyte spheroids. AB - 3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour. We measured metabolic parameters from single human HepaRG hepatocyte spheroids online and continuously with electrochemical microsensors. A microsensor platform for lactate and oxygen was integrated in a standard 96-well plate. Electrochemical microsensors for lactate and oxygen allow fast, precise and continuous long-term measurement of metabolic parameters directly in the microwell. The demonstrated capability to precisely detect small concentration changes by single spheroids is the key to access their metabolism. Lactate levels in the culture medium starting from 50uM with production rates of 5uMh-1 were monitored and precisely quantified over three days. Parallel long-term oxygen measurements showed no oxygen depletion or hypoxic conditions in the microwell. Increased lactate production by spheroids upon suppression of the aerobic metabolism was observed. The dose-dependent decrease in lactate production caused by the addition of the hepatotoxic drug Bosentan was determined. We showed that in a toxicological application, metabolic monitoring yields quantitative, online information on cell viability, which complements and supports other methods such as microscopy. The demonstrated continuous access to 3D cell culture metabolism within a standard setup improves in vitro toxicology models in replacement strategies of animal experiments. Controlling the microenvironment of such organotypic cultures has impact in tissue engineering, cancer therapy and personalized medicine. PMID- 27665517 TI - The capacitive sensing of NS1 Flavivirus biomarker. AB - NS1 is a biomarker for different Flavivirus diseases such as dengue (DENV), zika (ZIKV) and chikungunya (CHIKV) and was herein selectively quantified by electrochemical capacitive sensing (an impedance-derived capacitance methodology wherein the redox probe is contained in the receptive layer) mainly aiming dengue diagnosis in phosphate buffer saline and blood serum environments (up to the neat level). The capacitive sensing was compared to traditional concurrent impedimetric approach (in which the redox probe is added in the biological solution) and other transient methods stated in the literature regarding figures of merit such as limit of detection, linear range, relative standard deviation and affinity constant. Capacitive and impedimetric assays showed equivalent results for linear range, repeatability, sensitivity and constant of affinity. Nonetheless capacitive assays presented better reproducibility with a relative standard deviation (RSD) of 3+/-1 and 7+/-4 (all in percentage) in PBS and serum, respectively, meanwhile for impedimetric assays the RSD values were 9+/-5 in PBS and 12+/-6 in serum. Thus, by using capacitive assays, an improvement on the analytical performance was observed with the limit of detection about sixty-fold lower in neat serum (~0.5ngmL-1 for capacitive over ~30ngmL-1 for impedimetric assays) compared to traditional electrochemistry methods in general hence demonstrating the superior detection sensitivity for NS1 protein. Accordingly, redox tagged capacitive assays are suitable for the development of multiplex point-of-care neglected diseases sensing applications. PMID- 27665518 TI - 5,5-Dithiobis(2-nitrobenzoic acid) pyrene derivative-carbon nanotube electrodes for NADH electrooxidation and oriented immobilization of multicopper oxidases for the development of glucose/O2 biofuel cells. AB - We report the functionalization of multi-walled carbon nanotubes (MWCNTs) electrodes by a bifunctional nitroaromatic molecule accomplished via pi-pi interactions of a pyrene derivative. DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) has the particularity to possess both electroactivable nitro groups and negatively charged carboxylic groups. The integration of the DTNB-modified MWCNTs was evaluated for different bioelectrocatalytic systems. The immobilized DTNB based electrodes showed electrocatalytic activity toward the oxidation of the reduced form of nicotinamide adenine dinucleotide (NADH) with low overpotential of -0.09V vs Ag/AgCl at neutral pH. Glucose dehydrogenase was successfully immobilized at the surface of DTNB-based electrodes and, in the presence of NAD+, the resulting bioelectrode achieved efficient glucose oxidation with high current densities of 2.03mAcm-2. On the other hand, the aromatic structure and the negatively charged nature of the DTNB provoked orientation of both laccase and bilirubin oxidase onto the electrode, which enhanced their ability to undergo a direct electron transfer for oxygen reduction. Due to the proper orientation, low overpotentials were obtained (ca. 0.6V vs Ag/AgCl) and high electrocatalytic currents of about 3.5mAcm-2 were recorded at neutral pH in O2 saturated conditions for bilirubin oxidase electrodes. The combination of these bioanodes and bilirubin oxidase biocathodes provided glucose/O2 enzymatic biofuel cells (EBFC) exhibiting an open-circuit potential of 0.640V, with an associated maximum current density of 2.10mAcm-2. Moreover, the fuel cell delivered a maximum power density of 0.50mWcm-2 at 0.36 V. PMID- 27665519 TI - DNA-probe-target interaction based detection of Brucella melitensis by using surface plasmon resonance. AB - Surface plasmon resonance (SPR) immunosensor using 4-mercaptobenzoic acid (4-MBA) modified gold (4-MBA/Au) SPR chip was developed first time for the detection of Brucella melitensis (B. melitensis) based on the screening of its complementary DNA target by using two different newly designed DNA probes of IS711 gene. Herein, interaction between DNA probes and target molecule are also investigated and result revealed that the interaction is spontaneous. The kinetics and thermodynamic results derived from the experimental data showed that the interaction between complementary DNA targets and probe 1 is more effective than that of probe 2. Equilibrium dissociation constant (KD) and maximum binding capacity of analyte (Bmax) values for the interaction of complementary DNA target with the immobilized DNA probes were calculated by using kinetic evaluation software, and found to be 15.3 pM (KD) and 81.02m degrees (Bmax) with probe 1 and 54.9pM and 55.29m degrees (Bmax), respectively. Moreover, real serum samples analysis were also carried out using immobilized probe 1 and probe 2 with SPR which showed the applicability of this methodology and provides an alternative way for the detection of B. melitensis in less than 10min. This remarkable sensing response of present methodology offer a real time and label free detection of biological warfare agent and provide an opportunity to make miniaturized sensor, indicating considerable promise for diverse environmental, bio-defence, clinical diagnostics, food safety, water and security applications. PMID- 27665520 TI - The differential importance of mutations within AmpD in cephalosporin resistance of Enterobacter aerogenes and Enterobacter cloacae. AB - Mechanisms leading to carbapenem and cephalosporin resistance were sought in Enterobacter aerogenes isolates that were highly resistant to carbapenems but had no known carbapenemase. Results were compared with recent work examining carbapenem-resistant Enterobacter cloacae. Eighteen carbapenem-resistant E. aerogenes were screened for known beta-lactamase and carbapenemase genes, and novel carbapenemases were sought in whole-genome sequencing (WGS) data of the three most resistant isolates. For all isolates, ampC, ampR, ampD and the porin genes omp35 and omp36 were investigated by Sanger sequencing or from available WGS data. Expression of ampC and porin genes was measured in comparison with cephalosporin- and carbapenem-susceptible control strains by reverse transcriptase PCR, with porin translation also detected by SDS-PAGE. Loss of Omp35, primarily due to decreased transcription (up to 250*), was observed in ertapenem-resistant isolates (MICs >= 2 mg/L), whereas meropenem resistance (MICs >= 4 mg/L) was observed in those isolates also showing decreased or no production of Omp36. Loss of Omp36 was due to combinations of premature translation termination or reduced transcription. In contrast to E. cloacae, cephalosporin resistance in E. aerogenes was not associated with lesions in AmpD. High-level cefepime resistance (MIC = 32 mg/L) was caused by a novel modification in the H 10 helix of AmpC in one isolate. The differential importance of AmpD lesions in cephalosporin resistance in E. cloacae and E. aerogenes underlines the differences between these contrasting members of the Enterobacter genus. Porin loss resulted in high-level carbapenem resistance with gradual loss of Omp36, which led to high-level meropenem resistance. PMID- 27665521 TI - Is oral pristinamycin effective for the treatment of resistant Gram-positive infections as a relay after initial parenteral antimicrobial therapy? PMID- 27665522 TI - Pooled analysis of single-dose oritavancin in the treatment of acute bacterial skin and skin-structure infections caused by Gram-positive pathogens, including a large patient subset with methicillin-resistant Staphylococcus aureus. AB - Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The phase 3 studies SOLO I and SOLO II demonstrated comparable efficacy and safety of a single dose of oritavancin compared with 7-10 days of twice-daily vancomycin in adults with acute bacterial skin and skin-structure infections (ABSSSIs). The present analysis assessed clinical responses by pathogen at 48-72 h and at study days 14-24 in SOLO patients within the pooled data set. Of the 1959 patients in the pooled SOLO studies, 1067 had at least one baseline Gram positive pathogen and 405 had MRSA. Clinical response rates were similar for oritavancin- and vancomycin-treated patients by pathogen, including Staphylococcus aureus with or without the Panton-Valentine leukocidin (pvl) gene and from different clonal complexes, and were similar for pathogens within each treatment group. Oritavancin exhibited potent in vitro activity against all baseline pathogens, with MIC90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) of 0.12 ug/mL for Staphylococcus aureus, 0.25 ug/mL for Streptococcus pyogenes and 0.06 ug/mL for Enterococcus faecalis. Whereas both oritavancin and vancomycin achieved similarly high rates of clinical response by pathogen, including methicillin-susceptible and -resistant Staphylococcus aureus, oritavancin provides a single-dose alternative to 7-10 days of twice-daily vancomycin to treat ABSSSIs. PMID- 27665523 TI - Combination antimicrobial susceptibility testing of Burkholderia cepacia complex: significance of species. AB - The Burkholderia cepacia complex (Bcc) is notorious for the life-threatening pulmonary infections it causes in patients with cystic fibrosis. The multidrug resistant nature of Bcc and differing infective Bcc species make the design of appropriate treatment regimens challenging. Previous synergy studies have failed to take account of the species of Bcc isolates. Etest methodology was used to facilitate minimum inhibitory concentration (MIC) and antimicrobial combination testing on 258 isolates of Bcc, identified to species level by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). The most active antimicrobials were trimethoprim/sulphamethoxazole, doxycycline and minocycline (52.5%, 46.4% and 45.9% of isolates susceptible, respectively). Synergy was observed in 9.2% of the 1799 combinations tested; the most common synergistic combinations were tobramycin + ceftazidime, meropenem + tobramycin and levofloxacin + piperacillin/tazobactam (35.4%, 32.3% and 22.2% synergy, respectively). Antimicrobial susceptibility analysis revealed differences between Burkholderia cenocepacia and Burkholderia multivorans. Disparity in clinical outcome during infection with these two micro-organisms necessitates further investigation into the clinical outcomes of treatment regimens in light of species identification and in vitro antimicrobial susceptibility studies. PMID- 27665524 TI - 25 Years of the Onchocerca ochengi Model. AB - Although of limited veterinary significance, Onchocerca ochengi has become famous as a natural model or 'analogue' of human onchocerciasis (river blindness), which is caused by Onchocerca volvulus. On the basis of both morphological and molecular criteria, O. ochengi is the closest extant relative of O. volvulus and shares several key natural history traits with the human pathogen. These include exploitation of the same group of insect vectors (blackflies of the Simulium damnosum complex) and formation of collagenous nodules with a similar histological structure to human nodules. Here, we review the contribution of this natural system to drug and vaccine discovery efforts, as well as to our basic biological understanding of Onchocerca spp., over the past quarter-century. PMID- 27665526 TI - The retrieval of perceptual memory details depends on right hippocampal integrity and activation. AB - We assessed whether perceptual richness, a defining feature of episodic memory, depends on the engagement and integrity of the hippocampus during episodic memory retrieval. We tested participants' memory for complex laboratory events (LEs) that differed in perceptual content: short stories were either presented as perceptually rich film clips or as perceptually impoverished narratives. Participants underwent functional magnetic resonance imaging (fMRI) while retrieving these LEs (narratives and clips), as well as events from their personal life (autobiographical memories). In a group of healthy adults, a conjunction analysis showed that both real-life and laboratory memories engaged overlapping regions from an autobiographical memory (AM) retrieval network, indicating that laboratory memories mimicked autobiographical events successfully. A direct contrast between the film clip and the narrative laboratory conditions identified regions activated by the retrieval of perceptual memory content, which included the right hippocampus, parahippocampal gyrus, middle occipital gyrus and precuneus. In individuals with medial temporal lobe epilepsy (mTLE) originating from the right hippocampus, the magnitude of this "perceptually rich" signal was reduced significantly, which is consistent with evidence of reduced perceptual memory content in this clinical population. In healthy controls, right hippocampal activation also correlated positively with a behavioral measure of perceptual content in the clip condition. Thus, right hippocampal activity contributed to the retrieval of perceptual episodic memory content in the healthy brain, while right hippocampal damage disrupted activation in regions that process perceptual memory content. Our results suggest that the hippocampus contributes to recollection by retrieving and integrating perceptual details into vivid memory constructs. PMID- 27665525 TI - Standard triple therapy versus sequential therapy for eradication of Helicobacter pylori in treatment naive and retreat patients. AB - BACKGROUND AND STUDY AIMS: Untreated Helicobacter pylori infection causes increased risk of gastric cancer, GI morbidity and mortality. Standard treatment for eradication of Helicobacter pylori infection, is the triple therapy which consists of a proton pump inhibitor; together with two antibiotics (amoxicillin 1000mg with clarithromycin 500mg or metronidazole 400mg) given twice daily for 7 14days. Recent evidence revealed, that cure rates of Helicobacter pylori infection with triple therapy had fallen below satisfactory targets. Sequential therapy consisting of a twice daily dose of a PPI for ten days with Amoxicillin given at 1000mg twice daily in the first 5days followed by clarithromycin 500mg and Metronidazole 400mg given twice daily in the subsequent 5days, was recommended to improve eradication rates. We performed a randomised open label study to compare the efficacy of sequential against triple therapy in Helicobacter pylori naive and retreat patients. PATIENTS AND METHODS: In a randomised open label observational study 485 patients fulfilling inclusion and exclusion criteria were randomly assigned to be treated with triple therapy (n=231) or sequential therapy (n=254). Eradication of Helicobacter pylori was documented with 14C Urea breath test (UBT) performed 6weeks after the treatment. RESULTS: The intention-to-treat eradication rate was better in sequential therapy group 84.6% than triple therapy 68% (p<0.001). Eradication rates were significantly higher for treatment naive than retreat patients in triple therapy group (70.5% and 58.3%, respectively, p<0.01). A trend of a better response was observed in eradication rate for treatment naive 88.55% versus retreat 74.6% in sequential therapy group but was not statistically significant (p=0.76). Compliance was similar in the two groups, however side effects were less and the clinical response was better in the sequential therapy group. PMID- 27665527 TI - Development of a high-yielding bioprocess for 11-alpha hydroxylation of canrenone under conditions of oxygen-enriched air supply. AB - A high yielding bioprocess for 11-alpha hydroxylation of canrenone (1a) using Aspergillus ochraceus ATCC 18500 was developed. The optimization of the biotransformation involved both fermentation (for achieving highly active mycelium of A. ochraceus) and biotransformation with the aim to obtain 11-alpha hydroxylation with high selectivity and yield. A medium based on sucrose as C source resulted particularly suitable for conversion of canrenone into the corresponding 11-hydroxy derivative, whereas the use of O2-enriched air and dimethyl sulfoxide (DMSO) as a co-solvent for increasing substrate solubility played a crucial role for obtaining high yields (>95%) of the desired product in high chemical purity starting from 30mM (10.2g/L) of substrate. The structure of the hydroxylated product was confirmed by a combination of two-dimensional NMR proton-proton correlation techniques. PMID- 27665528 TI - Antimicrobial effects of vinegar against norovirus and Escherichia coli in the traditional Korean vinegared green laver (Enteromorpha intestinalis) salad during refrigerated storage. AB - In Korea, edible seaweeds are potentially regarded as high-risk foods with respect to enteric norovirus (NoV) and non-pathogenic generic Escherichia coli. This study investigated the antimicrobial effects of 5%, 10%, and 15% vinegar (6% acetic acid) on the survival of murine norovirus-1 (MNV-1), a human NoV surrogate, and E. coli, a fecal indicator in experimentally contaminated raw fresh green lavers (Enteromorpha intestinalis) during a 7-d storage period at 4 degrees C. Both MNV-1 titers and E. coli counts significantly (p<0.05) decreased with stepwise increase in vinegar concentration and storage time, except in E. coli of the 0% vinegar-containing lavers; however, MNV-1 was more resistant to vinegar than E. coli. The overall average MNV-1 titers were significantly (p<0.05) higher in 0% vinegar-containing lavers (3.6log10PFU/ml) than in 5-15% vinegar-containing lavers (3.3-3.1log10PFU/ml) throughout the 7days of storage. A 1-log reduction in the MNV-1 titer was observed in 0% vinegar-containing laver samples after 5days of storage and 5-15% vinegar-containing laver samples after 3days of storage. The overall E. coli count was also significantly (p<0.05) decreased in the 15% (6.8log10CFU/g) vinegar-containing lavers than in the 10% (7.3log10CFU/g) and 5% (7.6log10CFU/g) vinegar-containing lavers. A >1-log reduction in the E. coli count was observed in 10-15% vinegar-containing laver samples just after 1day of storage. A 2-log reduction in the E. coli count was also observed in 10-15% vinegar-containing laver samples after 5days of storage. Using the non-linear Weibull model, this study showed that the dR-values (1-log reduction) of MNV-1 were 4.90days for 0%, 4.28days for 5%, 3.79days for 10%, and 2.88days for 15% vinegar-containing lavers, whereas those for E. coli were 1.12day for 5%, 1.03day for 10%, and 0.90day for 15% vinegar-containing lavers stored at 4 degrees C. Vinegar with over the storage time can be used as an antimicrobial ingredient against NoV and E. coli in Korean conventional foods. Specifically, this study suggests that ~1day of storage is required for 1-log reduction in the E. coli count in the vinegar-containing (5-15%) lavers, whereas 3-5days of storage at 4 degrees C is adequate for 1-log reduction in the MNV-1 count in the vinegar-containing and non-vinegar-containing lavers. PMID- 27665529 TI - Evidence-based conservative rehabilitation for posterior glenohumeral instability: A systematic review. AB - STUDY DESIGN: Systematic review. OBJECTIVES: To identify the best evidenced-based approach for the conservative rehabilitation of patients with posterior glenohumeral instability. BACKGROUND: Posterior glenohumeral instability is more common than previously thought. Proper management is imperative to control symptoms and maximize function. METHODS: We conducted an electronic search, up to November 2014, for English-language studies involving rehabilitation of posterior shoulder instability. A manual search of reference lists of included articles and previously published reviews was also performed. RESULTS: Five studies met the review inclusion criteria. Most studies demonstrated that rotator cuff and posterior deltoid strengthening could reduce instability recurrence and pain, and increase function, mainly in those with atraumatic posterior instability without previous surgery. These studies were mainly case series or retrospective designs. CONCLUSIONS: Rotator cuff and posterior deltoid strengthening may help with symptom-management and functioning in those with posterior glenohumeral instability. Further research is needed to detect statistically significant outcomes from conservative treatment. LEVEL OF EVIDENCE: Therapy, Level 3. PMID- 27665530 TI - Synthesis of citric acid functionalized magnetic graphene oxide coated corn straw for methylene blue adsorption. AB - The citric acid functionalized magnetic graphene oxide coated corn straw (CA mGOCS) as a new adsorbent was synthesized in this work for the elimination of methylene blue (MB) from waste water. The as-prepared CA-mGOCS was tested by SEM, FTIR, XRD, Roman spectrum, TGA, particle size analyzer, BET and magnetic properties analyzer. Some factors affecting adsorption removal efficiency were explored. As a result, the addition of 5g CS (CA-mGO5CS) had the better adsorption performance than other adsorbents. The pseudo-second-order model and the Freundlich described the adsorption behavior well. The equilibrium adsorption capacity was 315.5mgg-1 for MB at pH=12 and 298k. The electrostatic incorporation as well as hydrophobic interactions between CA-mGO5CS and MB determined the favourable adsorption property. Besides, the thermodynamic studies results DeltaG<0, DeltaH<0, DeltaS<0 suggested that the adsorption was a spontaneous, exothermic and randomness decrease process. Finally, reusability studies imply that CA-mGO5CS has an excellent reproducibility. PMID- 27665531 TI - Augmentation of arsenic enhances lipid yield and defense responses in alga Nannochloropsis sp. AB - The present study was conducted with microalga Nannochloropsis sp. to evaluate its tolerance responses and biofuel perspectives under different arsenic regime (0-1000MUM As(III)). Results showed that optimal biomass (61.00+/-3.72mg/L/d) and lipid productivity (20.27mg/L/d) were obtained in culture treated with 100MUM As(III) in comparison to other treatments. In addition, fatty acid profile of alga was in accordance with European biodiesel standards (EN 14214), which reflects good oxidative stability of oil. High antioxidants viz., ascorbic acid, GSH and cysteine tolerance responses as well as lipid yield at 100MUM As(III), opens a new insight in the field of algal biology. Thus, microalgae Nannochloropsis sp. may be employ in remediation as well as biodiesel production. PMID- 27665532 TI - Multi-window detection for P-wave in electrocardiograms based on bilateral accumulative area. AB - BACKGROUND AND OBJECTIVE: P-wave detection is one of the most challenging aspects in electrocardiograms (ECGs) due to its low amplitude, low frequency, and variable waveforms. This work introduces a novel multi-window detection method for P-wave delineation based on the bilateral accumulative area. METHOD: The bilateral accumulative area is calculated by summing the areas covered by the P wave curve with left and right sliding windows. The onset and offset of a positive P-wave correspond to the local maxima of the area detector. The position drift and difference in area variation of local extreme points with different windows are used to systematically combine multi-window and 12-lead synchronous detection methods, which are used to screen the optimization boundary points from all extreme points of different window widths and adaptively match the P-wave location. RESULTS: The proposed method was validated with ECG signals from various databases, including the Standard CSE Database, T-Wave Alternans Challenge Database, PTB Diagnostic ECG Database, and the St. Petersburg Institute of Cardiological Technics 12-Lead Arrhythmia Database. The average sensitivity Se was 99.44% with a positive predictivity P+ of 99.37% for P-wave detection. Standard deviations of 3.7 and 4.3ms were achieved for the onset and offset of P waves, respectively, which is in agreement with the accepted tolerances required by the CSE committee. CONCLUSION: Compared with well-known delineation methods, this method can achieve high sensitivity and positive predictability using a simple calculation process. The experiment results suggest that the bilateral accumulative area could be an effective detection tool for ECG signal analysis. PMID- 27665533 TI - The R implementation of the CRAN package PATHChange, a tool to study genetic pathway alterations in transcriptomic data. AB - Tools that extract phenotype alterations from transcriptomic data are important to improve the interpretation of biological studies. PATHChange is a statistical CRAN package designed to work with data downloaded from the Gene Expression Omnibus database (GEO) to determine differential pathway expression in comparative studies including control samples. In this paper we present details of the structure, implementation and an example of use of the package. PMID- 27665534 TI - Hidden discriminative features extraction for supervised high-order time series modeling. AB - In this paper, an orthogonal Tucker-decomposition-based extraction of high-order discriminative subspaces from a tensor-based time series data structure is presented, named as Tensor Discriminative Feature Extraction (TDFE). TDFE relies on the employment of category information for the maximization of the between class scatter and the minimization of the within-class scatter to extract optimal hidden discriminative feature subspaces that are simultaneously spanned by every modality for supervised tensor modeling. In this context, the proposed tensor decomposition method provides the following benefits: i) reduces dimensionality while robustly mining the underlying discriminative features, ii) results in effective interpretable features that lead to an improved classification and visualization, and iii) reduces the processing time during the training stage and the filtering of the projection by solving the generalized eigenvalue issue at each alternation step. Two real third-order tensor-structures of time series datasets (an epilepsy electroencephalogram (EEG) that is modeled as channel*frequency bin*time frame and a microarray data that is modeled as gene*sample*time) were used for the evaluation of the TDFE. The experiment results corroborate the advantages of the proposed method with averages of 98.26% and 89.63% for the classification accuracies of the epilepsy dataset and the microarray dataset, respectively. These performance averages represent an improvement on those of the matrix-based algorithms and recent tensor-based, discriminant-decomposition approaches; this is especially the case considering the small number of samples that are used in practice. PMID- 27665535 TI - Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder. AB - OBJECTIVE: Cardiovascular risk factors (CVRFs) and impulsivity are common in bipolar disorder (BD), and CVRFs are also linked with impulsivity through a number of mechanisms, both behavioral and biological. This study examines the association between CVRFs and impulsivity in adolescents with BD. METHODS: Subjects were 34 adolescents with BD and 35 healthy control (HC) adolescents. CVRFs were based on International Diabetes Federation metabolic syndrome criteria (triglycerides, high-density lipoprotein cholesterol, waist circumference, blood pressure (BP) and glucose). Impulsivity was measured using the computerized Cambridge Gambling Task (CGT). Analyses controlled for age, IQ, lifetime attention deficit hyperactivity disorder, and current antipsychotic use. RESULTS: Adolescents with BD had higher diastolic BP (73.36 +/- 9.57 mmHg vs. 67.91 +/- 8.74 mmHg, U = 401.0, p = 0.03), higher triglycerides (1.13 +/- 0.60 mmol/L vs. 0.78 +/- 0.38 mmol/L, U = 373.5, p = 0.008), and were more likely to meet high risk criteria for waist circumference (17.6% vs. 2.9%, p = 0.04) vs. HC. Within the BD group, CGT sub-scores were correlated with CVRFs. For example, overall proportion bet was positively correlated with systolic (r = 0.387, p = 0.026) and diastolic (rho = 0.404, p = 0.020) BP. Quality of decision-making was negatively correlated with systolic BP (rho = -0.401, p = 0.021) and waist circumference (rho = -0.534, p = 0.003). Significant interactions were observed, such that BD diagnosis moderates the relationship between both waist circumference and BP with CGT sub-scores. CONCLUSION: BP and waist circumference are associated with impulsivity in BD adolescents, but not in HC adolescents. Future studies are warranted to determine temporality and to evaluate whether optimizing CVRFs improves impulsivity among BD adolescents. PMID- 27665536 TI - Atomoxetine for hoarding disorder: A pre-clinical and clinical investigation. AB - Despite several studies suggested that inattention and impulsivity-compulsivity could represent two core dimensions of hoarding disorder (HD), only a small case series study investigated the effectiveness of attention-deficit-hyperactivity disorder (ADHD) medications in HD. The aim of the present study was to target attentional and inhibitory control networks in HD patients through the ADHD medication atomoxetine, moving from a preclinical investigation on an animal model of compulsive-like behavior (marble burying test) to a clinical investigation on both medicated and unmedicated patients with a primary diagnosis of HD without ADHD. Our preclinical investigation showed that acute administration of atomoxetine significantly reduced the compulsive-like behaviours of mice in the marble burying test without affecting neither locomotor activity and coordination nor exploration behaviours. When compared, atomoxetine and fluoxetine showed similar effects on the marble burying test. However, fluoxetine impaired both locomotor and exploratory activity. In our clinical investigation 12 patients were enrolled and 11 patients completed an open trial with atomoxetine at flexible dose (40-80 mg) for 12 weeks. At the endpoint the mean UCLA Hoarding Severity Scale score decreased by 41.3% for the whole group (p = 0003). Six patients were classified as full responders (mean symptom reduction of 57.2%) and three patients as partial responders (mean symptom reduction of 27.3%). Inattentive and impulsivity symptoms showed a significant mean score reduction of 18.5% from baseline to the endpoint (F (1,9) = 20.9, p = 0.0013). Hoarding symptoms improvement was correlated to reduction of patients' disability and increased in their global functioning. These preclinical and clinical data suggest that atomoxetine may be effective for HD and therefore should be considered for future controlled trials. PMID- 27665537 TI - Usefulness of dyssynchrony indices based on two-dimensional speckle tracking echocardiography in a canine model of left bundle branch block. AB - INTRODUCTION: Determine the usefulness of dyssynchrony indices derived from two dimensional speckle tracking echocardiography for the detection of mechanical dyssynchrony in a canine model of left bundle branch block. ANIMALS: Ten healthy beagles. MATERIALS AND METHODS: Segmental, time-radial strain curves were obtained using two-dimensional speckle tracking echocardiography. The maximum difference and standard deviation of the time to peak radial strain for six predefined segments (MaxD-TpSR and 6SD-TpSR) were calculated, together with the left ventricular dyssynchrony by radial strain (DysSR), before and after ablation of the left bundle branch block. Receiver operating characteristic curve analysis was performed using dogs after ablation as positive controls. RESULTS: After ablation, all dogs showed multiple peaks in at least one segment on the time radial strain curve, while all dyssynchrony indices increased significantly (MaxD TpSR from 16.25 +/- 16.04 [mean +/- standard deviation] to 44.4 +/- 26.18 ms, 6SD TpSR from 7.59 +/- 7.40 to 19.62 +/- 11.91 ms, and DysSR from 4.20 +/- 2.12 to 10.87+/- 2.92%, p<0.05). In receiver operating characteristic curve analysis, the areas under the curve for MaxD-TpSR, 6SD-TpSR, and DysSR were 0.825, 0.800, and 0.980, respectively. CONCLUSIONS: Left ventricular dyssynchrony by radial strain can detect mechanical dyssynchrony with higher sensitivity and specificity than dyssynchrony indices, based on the time to peak radial strain. PMID- 27665538 TI - Alternative methods for the measurement of the minimal ductal diameter of a patent ductus arteriosus in a dog. AB - A two and half-year-old, 24 kg, spayed female German Shepherd was presented for evaluation of a suspected patent ductus arteriosus (PDA). Transthoracic echocardiographic examination confirmed a left to right shunting PDA. Closure of the PDA was recommended, and the owners elected to have minimally invasive transcatheter closure of the PDA performed. Standard ductal angiography failed to provide adequate measurements of the minimal ductal diameter (MDD). Alternative methods of measuring the MDD using an angiography catheter and a balloon catheter were performed. The PDA was occluded using an Amplatz(r) Canine Ductal Occluder without complication. Further evaluation of these techniques is needed to determine the accuracy, overall clinical efficacy, and safety of using alternative methods for the measurement of the MDD of a PDA. PMID- 27665540 TI - Nab-paclitaxel for the treatment of triple-negative breast cancer: Rationale, clinical data and future perspectives. AB - Triple-negative breast cancer (TNBC) accounts for ~10-20% of breast cancers and is associated with relatively poor prognosis, earlier disease recurrence and higher number of visceral metastases. Despite an increasing understanding of the molecular heterogeneity of TNBC, clinical trials of targeted agents have thus far been disappointing; chemotherapy, in particular with anthracycline and taxanes, remains the backbone medical management for both early and metastatic TNBC. Nab paclitaxel is a solvent-free, albumin-bound, nanoparticle formulation of paclitaxel and represents a novel formulation of an established, effective chemotherapeutic agent. Nab-paclitaxel has been specifically designed to overcome the limitations of conventional taxane formulations, including the barriers to effective drug delivery of highly lipophilic agents. It has shown significant efficacy and better tolerability than conventional taxanes in metastatic breast cancer and is approved for use in this setting. Increasing evidence suggests that nab-paclitaxel is effective in patients with more aggressive tumours, as seen in TNBC. Indeed, results of Phase II/III studies indicate that nab-paclitaxel may be effective as neoadjuvant treatment of TNBC. This article reviews the rationale and evidence supporting a role for nab-paclitaxel in the treatment of TNBC, including ongoing studies such as ADAPT-TN and tnAcity. In addition, the article reviews ongoing research into targeted therapies and immuno-oncology for the treatment of TNBC, and explores the potential role, current evidence and ongoing studies of nab-paclitaxel as the chemotherapy partner in combination with immunotherapy, where the unique properties of this taxane, including the lack of requirement for steroid pre-medication, may present an advantage. PMID- 27665541 TI - Degradation of two novel congenital TTP ADAMTS13 mutants by the cell proteasome prevents ADAMTS13 secretion. AB - INTRODUCTION: Over 150 mutations have been identified in the ADAMTS13 gene in patients with congenital thrombotic thrombocytopenic purpura (TTP). The majority of these (86%), lead to reduced (<50%) secretion of mutant recombinant ADAMTS13. The mechanism by which this occurs has not been investigated in vitro. Two novel ADAMTS13 mutations (p.I143T and p.Y570C) identified in two congenital adolescence onset TTP patients were studied, to investigate their effects on ADAMTS13 secretion and subcellular localisation. MATERIALS AND METHODS: HEK293T cells were transiently transfected with wild type or mutant ADAMTS13 cDNA. Immunofluorescence and confocal microscopy were used to study localisation within the endoplasmic reticulum (ER) and Golgi. The cell proteasome and lysosomes were inhibited in cells stably expressing ADAMTS13 to investigate degradation of ADAMTS13 by either organelle. RESULTS: Both mutations severely impaired secretion and both mutants localised within the ER and Golgi. Proteasome inhibition led to the intracellular accumulation of both mutants, suggesting proteasome degradation. Lysosome inhibition on the other hand did not lead to increased intracellular accumulation of the mutants. CONCLUSIONS: Proteasome degradation of these ADAMTS13 mutants contributed to their reduced secretion. PMID- 27665539 TI - Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer. AB - The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non miliary, possibly due to the active down-regulation of anti-tumor responses by B cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID- 27665542 TI - Generalist predator, cyclic voles and cavity nests: testing the alternative prey hypothesis. AB - The alternative prey hypothesis (APH) states that when the density of the main prey declines, generalist predators switch to alternative prey and vice versa, meaning that predation pressure on the alternative prey should be negatively correlated with the density of the main prey. We tested the APH in a system comprising one generalist predator (pine marten, Martes martes), cyclic main prey (microtine voles, Microtus agrestis and Myodes glareolus) and alternative prey (cavity nests of common goldeneye, Bucephala clangula); pine marten is an important predator of both voles and common goldeneye nests. Specifically, we studied whether annual predation rate of real common goldeneye nests and experimental nests is negatively associated with fluctuation in the density of voles in four study areas in southern Finland in 2000-2011. Both vole density and nest predation rate varied considerably between years in all study areas. However, we did not find support for the hypothesis that vole dynamics indirectly affects predation rate of cavity nests in the way predicted by the APH. On the contrary, the probability of predation increased with vole spring abundance for both real and experimental nests. Furthermore, a crash in vole abundance from previous autumn to spring did not increase the probability of predation of real nests, although it increased that of experimental nests. We suggest that learned predation by pine marten individuals, coupled with efficient search image for cavities, overrides possible indirect positive effects of high vole density on the alternative prey in our study system. PMID- 27665543 TI - Environmental filtering of eudicot lineages underlies phylogenetic clustering in tropical South American flooded forests. AB - The phylogenetic community assembly approach has been used to elucidate the role of ecological and historical processes in shaping tropical tree communities. Recent studies have shown that stressful environments, such as seasonally dry, white-sand and flooded forests tend to be phylogenetically clustered, arguing for niche conservatism as the main driver for this pattern. Very few studies have attempted to identify the lineages that contribute to such assembly patterns. We aimed to improve our understanding of the assembly of flooded forest tree communities in Northern South America by asking the following questions: are seasonally flooded forests phylogenetically clustered? If so, which angiosperm lineages are over-represented in seasonally flooded forests? To assess our hypotheses, we investigated seasonally flooded and terra firme forests from the Magdalena, Orinoco and Amazon Basins, in Colombia. Our results show that, regardless of the river basin in which they are located, seasonally flooded forests of Northern South America tend to be phylogenetically clustered, which means that the more abundant taxa in these forests are more closely related to each other than expected by chance. Based on our alpha and beta phylodiversity analyses we interpret that eudicots are more likely to adapt to extreme environments such as seasonally flooded forests, which indicates the importance of environmental filtering in the assembly of the Neotropical flora. PMID- 27665544 TI - Fires can benefit plants by disrupting antagonistic interactions. AB - Fire has a key role in the ecology and evolution of many ecosystems, yet its effects on plant-insect interactions are poorly understood. Because interacting species are likely to respond to fire differently, disruptions of the interactions are expected. We hypothesized that plants that regenerate after fire can benefit through the disruption of their antagonistic interactions. We expected stronger effects on interactions with specialist predators than with generalists. We studied two interactions between two Mediterranean plants (Ulex parviflorus, Asphodelus ramosus) and their specialist seed predators after large wildfires. In A. ramosus we also studied the generalist herbivores. We sampled the interactions in burned and adjacent unburned areas during 2 years by estimating seed predation, number of herbivores and fruit set. To assess the effect of the distance to unburned vegetation we sampled plots at two distance classes from the fire perimeter. Even 3 years after the fires, Ulex plants experienced lower seed damage by specialists in burned sites. The presence of herbivores on Asphodelus decreased in burned locations, and the variability in their presence was significantly related to fruit set. Generalist herbivores were unaffected. We show that plants can benefit from fire through the disruption of their antagonistic interactions with specialist seed predators for at least a few years. In environments with a long fire history, this effect might be one additional mechanism underlying the success of fire-adapted plants. PMID- 27665545 TI - Twisting method for reducing friction during insertion of a sheath introducer and a sheathless guiding catheter. AB - A sheathless system that inserts a catheter directly into the artery can reduce puncture site-related complications through a 2-Fr reduction of the outer diameter. However, the gap between the dilator and the guiding catheter of the sheathless system is larger than the gap between the dilator and sheath of the introducer system, resulting in stronger insertion resistance. A twisting method with rapid alternating rotation of a device to the left and right during insertion can reduce the insertion resistance. This method can be effective with the sheathless system which has a larger gap. To examine the effect of size reduction on the sheathless system and the effect of insertion resistance reduction using the twisting method, we developed an insertion simulator and compared insertion resistance to a 5-Fr sheath introducer and a 5-Fr sheathless system, with and without the twisting method. The insertion simulator pushed a sheath introducer or a sheathless system toward a mock artery consisted with a 5 mm urethane and a 1-mm rubber sheet by an electrical motor with or without twisting motion generated by a crank shaft. Insertion resistance during the penetration was measured by a tension meter. The insertion resistance was less with the 5-Fr sheathless system than with the 5-Fr sheath introducer. The resistance reduced further with use of twisting for both the sheathed and sheathless catheters. In conclusion, the experiment suggests the benefits of twisting insertion of a sheathless guiding catheter for reduction of puncture site-related complications. PMID- 27665546 TI - Concordance Between Laboratory Diagnosed Sexually Transmitted Infections and Self Reported Measures of Risky Sex by Partner Type Among Rural Ugandan Outpatients. AB - Numerous HIV risk reduction interventions which show effects on sexual risk behaviors fail to find effects on STIs. We examined the concordance between laboratory diagnosed STIs and sexual risk behavior among Ugandan outpatients (n = 328). We screened for STIs and assessed sexual behavior at baseline and 6 month follow-up. Less risk was associated with an STI at baseline. At follow-up more unprotected sex with casual partners was associated with incident Syphilis, more unprotected sex with primary and secondary regular partners was associated with incident Chlamydia or Gonorrhea. Our results suggest ways to improve concordance between behavioral measures and STIs. PMID- 27665548 TI - ER to Golgi-Dependent Protein Secretion: The Conventional Pathway. AB - Secretion is the cellular process present in every organism that delivers soluble proteins and cargoes to the extracellular space. In eukaryotes, conventional protein secretion (CPS) is the trafficking route that secretory proteins undertake when are transported from the endoplasmic reticulum (ER) to the Golgi apparatus (GA), and subsequently to the plasma membrane (PM) via secretory vesicles or secretory granules. This book chapter recalls the fundamental steps in cell biology research contributing to the elucidation of CPS; it describes the most prominent examples of conventionally secreted proteins in eukaryotic cells and the molecular mechanisms necessary to regulate each step of this process. PMID- 27665549 TI - Unconventional Protein Secretion in Animal Cells. AB - All eukaryotic cells secrete a range of proteins in a constitutive or regulated manner through the conventional or canonical exocytic/secretory pathway characterized by vesicular traffic from the endoplasmic reticulum, through the Golgi apparatus, and towards the plasma membrane. However, a number of proteins are secreted in an unconventional manner, which are insensitive to inhibitors of conventional exocytosis and use a route that bypasses the Golgi apparatus. These include cytosolic proteins such as fibroblast growth factor 2 (FGF2) and interleukin-1beta (IL-1beta), and membrane proteins that are known to also traverse to the plasma membrane by a conventional process of exocytosis, such as alpha integrin and the cystic fibrosis transmembrane conductor (CFTR). Mechanisms underlying unconventional protein secretion (UPS) are actively being analyzed and deciphered, and these range from an unusual form of plasma membrane translocation to vesicular processes involving the generation of exosomes and other extracellular microvesicles. In this chapter, we provide an overview on what is currently known about UPS in animal cells. PMID- 27665547 TI - Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in isolated rat amygdala: the possible role of CREB/BDNF signaling pathway. AB - Methylphenidate (MPH) abuse damages brain cells. The neuroprotective effects of topiramate (TPM) have been reported previously, but its exact mechanism of action still remains unclear. This study investigated the in vivo role of various doses of TPM in the protection of rat amygdala cells against methylphenidate-induced oxidative stress and inflammation. Seventy adult male rats were divided into seven groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg), respectively, for 21 days. Groups 3, 4, 5, 6, and 7 were concurrently treated with MPH (10 mg/kg) and TPM (10, 30, 50, 70, and 100 mg/kg), respectively, for 21 days. elevated plus maze (EPM) was used to assess motor activity disturbances. In addition, oxidative, antioxidantand inflammatory factors and CREB, Ak1, CAMK4, MAPK3, PKA, BDNF, and c FOS gene levels were measured by RT-PCR, and also, CREB and BDNF protein levels were measured by WB in isolated amygdalae. MPH significantly disturbed motor activity and TPM (70 and 100 mg/kg) neutralized its effects. MPH significantly increased lipid peroxidation, mitochondrial GSSG levels and IL-1beta and TNF-alpha level and CAMK4 gene expression in isolated amygdala cells. In contrast, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and CREB, BDNF Ak1, MAPK3, PKA, BDNF, and c FOS expression significantly decreased. The various doses of TPM attenuated these effects of MPH. It seems that TPM can be used as a neuroprotective agent and is a good candidate against MPH-induced neurodegeneration. PMID- 27665550 TI - Unconventional Protein Secretion in Plants. AB - Unconventional protein secretion (UPS) describes secretion pathways that bypass one or several of the canonical secretion pit-stops on the way to the plasma membrane, and/or involve the secretion of leaderless proteins. So far, alternatives to conventional secretion were primarily observed and studied in yeast and animal cells. The sessile lifestyle of plants brings with it unique restraints on how they adapt to adverse conditions and environmental challenges. Recently, attention towards unconventional secretion pathways in plant cells has substantially increased, with the large number of leaderless proteins identified through proteomic studies. While UPS pathways in plants are certainly not yet exhaustively researched, an emerging notion is that induction of UPS pathways is correlated with pathogenesis and stress responses. Given the multitude UPS events observed, comprehensively organizing the routes proteins take to the apoplast in defined UPS categories is challenging. With the establishment of a larger collection of studied plant proteins taking these UPS pathways, a clearer picture of endomembrane trafficking as a whole will emerge. There are several novel enabling technologies, such as vesicle proteomics and chemical genomics, with great potential for dissecting secretion pathways, providing information about the cargo that travels along them and the conditions that induce them. PMID- 27665551 TI - Chemical Secretory Pathway Modulation in Plant Protoplasts. AB - The classical Golgi pathway is not the only mechanism for vacuolar protein transport in plants because alternative transport mechanisms have been described. The existence of these alternative pathways can be demonstrated using several chemicals and here we describe the use of brefeldin A (BFA), endo-beta-N acetylglucosaminidase H (Endo-H), and tunicamycin, on isolated tobacco leaf protoplasts. Two main methods are illustrated in this chapter, protoplast pulse chase followed by protein immunoprecipitation, and protoplast immunofluorescence. PMID- 27665552 TI - From Cytosol to the Apoplast: The Hygromycin Phosphotransferase (HYG(R)) Model in Arabidopsis. AB - The process by which proteins are secreted via endoplasmic reticulum (ER)/Golgi independent mechanism is conveniently called unconventional protein secretion. Recent studies have revealed that unconventional protein secretion operates in plants, but little is known about its underlying mechanism and function. This chapter provides methods we have used to analyze unconventional character of hygromycin phosphotransferase (HYG(R)) secretion in plant cells. Following isolation of protoplasts from HYG (R) -GFP-transgenic plants and incubation with brefeldin A (BFA), an inhibitor of conventional secretory pathway, we easily obtain protein extracts from protoplasts and culture medium separately. These proteins are separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by Western blot analysis with anti-GFP antibodies. PMID- 27665553 TI - Following the Time-Course of Post-pollination Events by Transmission Electron Microscopy (TEM): Buildup of Exosome-Like Structures with Compatible Pollinations. AB - In the Brassicaceae, the dry stigma is an initial barrier to pollen acceptance as the stigmatic papillae lack surface secretions, and consequently rapid cellular responses are required to accept compatible pollen. Regulated secretion with secretory vesicles or multivesicular bodies is initiated in the stigmatic papillae towards the compatible pollen grain. In self-incompatible species, this basal compatible pollen response is superseded by the self-incompatibility signaling pathway where the secretory organelles are found in autophagosomes and vacuole for destruction. In this chapter, we describe a detailed protocol using the Transmission Electron Microscope to document the rapid cellular changes that occur in the stigmatic papillae in response to compatible versus self incompatible pollen, at the pollen-stigma interface. PMID- 27665554 TI - Investigating Alternative Transport of Integral Plasma Membrane Proteins from the ER to the Golgi: Lessons from the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). AB - Secretory traffic became a topical field because many important cell regulators are plasma membrane proteins (transporters, channels, receptors), being thus key targets in biomedicine and drug discovery. Cystic fibrosis (CF), caused by defects in a single gene encoding the CF transmembrane conductance regulator (CFTR), constitutes the most common of rare diseases and certainly a paradigmatic one.Here we focus on five different approaches that allow biochemical and cellular characterization of CFTR from its co-translational insertion into the ER membrane to its delivery to the plasma membrane. PMID- 27665555 TI - Quantification of a Non-conventional Protein Secretion: The Low-Molecular-Weight FGF-2 Example. AB - Quantification of secreted factors is most often measured with enzyme-linked immunosorbent assay (ELISA), Western Blot, or more recently with antibody arrays. However, some of these, like low-molecular-weight fibroblast growth factor-2 (LMW FGF-2; the 18 kDa form), exemplify a set of secreted but almost non-diffusible molecular actors. It has been proposed that phosphorylated FGF-2 is secreted via a non-vesicular mechanism and that heparan sulfate proteoglycans function as extracellular reservoir but also as actors for its secretion. Heparan sulfate is a linear sulfated polysaccharide present on proteoglycans found in the extracellular matrix or anchored in the plasma membrane (syndecan). Moreover the LMW FGF-2 secretion appears to be activated upon FGF-1 treatment. In order to estimate quantification of such factor export across the plasma membrane, technical approaches are presented (evaluation of LMW FGF-2: (1) secretion, (2) extracellular matrix reservoir, and (3) secretion modulation by surrounding factors) and the importance of such procedures in the comprehension of the biology of these growth factors is underlined. PMID- 27665556 TI - Human Primary Keratinocytes as a Tool for the Analysis of Caspase-1-Dependent Unconventional Protein Secretion. AB - Inflammasomes comprise a group of protein complexes, which activate the protease caspase-1 upon sensing a variety of stress factors. Active caspase-1 in turn cleaves and thereby activates the pro-inflammatory cytokines prointerleukin (IL) 1beta and -18, and induces unconventional protein secretion (UPS) of mature IL 1beta, IL-18, as well as of many other proteins involved in and required for induction of inflammation. Human primary keratinocytes (HPKs) represent epithelial cells able to activate caspase-1 in an inflammasome-dependent manner upon irradiation with a physiological dose of ultraviolet B (UVB) light. Here, we describe the isolation of keratinocytes from human skin, their cultivation, and induction of caspase-1-dependent UPS upon UVB irradiation as well as its siRNA- and chemical-mediated inhibition. In contrast to inflammasome activation of professional immune cells, UVB-irradiated HPKs represent a robust and physiological cell culture system for the analysis of UPS induced by active caspase-1. PMID- 27665557 TI - A Reporter System to Study Unconventional Secretion of Proteins Avoiding N Glycosylation in Ustilago maydis. AB - Unconventional secretion of proteins in eukaryotes is characterized by the circumvention of the Endoplasmic Reticulum (ER). As a consequence proteins exported by unconventional pathways lack N-glycosylation, a post-transcriptional modification that is initiated in the ER during classical secretion. We are exploiting the well-established enzyme beta-glucuronidase (GUS) to assay unconventional protein secretion (UPS). This bacterial protein is perfectly suited for this purpose because it carries a eukaryotic N-glycosylation motif. Modification of this residue by attachment of sugar moieties during the passage of the ER apparently causes a very strong reduction in GUS activity. Hence, this enzyme can only be secreted in an active state, if the export mechanism does not involve ER passage. Here, we describe a reporter system applied in the corn smut fungus Ustilago maydis that is based on this observation and can be used to test if candidate proteins are secreted to the culture supernatant via alternative pathways avoiding N-glycosylation. Importantly, this system is the basis for the establishment of genetic screens providing mechanistic insights into unknown UPS pathways in the future. PMID- 27665558 TI - Stress-Inducible Protein 1 (STI1): Extracellular Vesicle Analysis and Quantification. AB - This chapter is derived from our experience in the study of stress-Inducible Protein 1 (STI1) in extracellular vesicles. We used different techniques to isolate, explore, and characterize the extracellular vesicles that contained this protein. Ultracentrifugation and gel chromatography were used to isolate extracellular vesicles of different sizes, nanotracking particle analysis (NTA) determined number and size of vesicles, while flow cytometry and ELISA were used to determine the specific protein content of vesicles. PMID- 27665559 TI - Analysis of Yeast Extracellular Vesicles. AB - Extracellular vesicles (EV) are important carriers of biologically active components in a number of organisms, including fungal cells. Experimental characterization of fungal EVs suggested that these membranous compartments are likely involved in the regulation of several biological events. In fungal pathogens, these events include mechanisms of disease progression and/or control, suggesting potential targets for therapeutic intervention or disease prophylaxis. In this manuscript we describe methods that have been used in the last 10 years for the characterization of EVs produced by yeast forms of several fungal species. Experimental approaches detailed in this chapter include ultracentrifugation methods for EV fractionation, chromatographic approaches for analysis of EV lipids, microscopy techniques for analysis of both intracellular and extracellular vesicular compartments, interaction of EVs with host cells, and physical chemical analysis of EVs by dynamic light scattering. PMID- 27665560 TI - Exploring the Leishmania Hydrophilic Acylated Surface Protein B (HASPB) Export Pathway by Live Cell Imaging Methods. AB - Leishmania major is a human-infective protozoan parasite transmitted by the bite of the female phlebotomine sand fly. The L. major hydrophilic acylated surface protein B (HASPB) is only expressed in infective parasite stages suggesting a role in parasite virulence. HASPB is a "nonclassically" secreted protein that lacks a conventional signal peptide, reaching the cell surface by an alternative route to the classical ER-Golgi pathway. Instead HASPB trafficking to and exposure on the parasite plasma membrane requires dual N-terminal acylation. Here, we use live cell imaging methods to further explore this pathway allowing visualization of key events in real time at the individual cell level. These methods include live cell imaging using fluorescent reporters to determine the subcellular localization of wild type and acylation site mutation HASPB18-GFP fusion proteins, fluorescence recovery after photobleaching (FRAP) to analyze the dynamics of HASPB in live cells, and live antibody staining to detect surface exposure of HASPB by confocal microscopy. PMID- 27665561 TI - Characterization of the Unconventional Secretion of the Ebola Matrix Protein VP40. AB - While most secreted proteins use the classical endoplasmic reticulum (ER)-Golgi secretion pathway to reach the extracellular medium, a few proteins are secreted through unconventional secretary pathways. Viral proteins can be secreted through unconventional secretion pathways. Here, we describe how we have recently demonstrated that the Ebola virus (EBOV) matrix protein VP40 is released from transfected and infected cells in a soluble form through an unconventional secretion pathway. PMID- 27665562 TI - Role and Characterization of Synuclein-gamma Unconventional Protein Secretion in Cancer Cells. AB - Synuclein-gamma (SNCG), the third member of synuclein family, is implicated in both neurodegenerative diseases and cancer. Overexpression of SNCG in cancer cells is linked to tumor progression and chemoresistance. Without any known signal sequence required for conventional protein secretion, SNCG is elevated in the serum of cancer patients and the medium of cultured cancer cells. SNCG actively secretes from cancer cells and extracellular SNCG promotes malignant phenotypes of cancer cells. Here, we describe methods for the characterization of SNCG as an unconventional secretion protein from cancer cells and investigation of the effect of extracellular SNCG on the phenotypes of cancer cells. PMID- 27665564 TI - Vacuum Infiltration-Centrifugation Method for Apoplastic Protein Extraction in Grapevine. AB - The apoplastic fluid moving in the extracellular space external to the plasma membrane provides a means of delivering molecules and facilitates intercellular communications. However, the apoplastic fluid extraction from in planta systems remains challenging and this is particularly true for grapevine (Vitis vinifera L.), a worldwide-cultivated fruit plant. Here, we describe an optimized vacuum infiltration-centrifugation method to extract soluble proteins from apoplastic fluid of grapevine leaves. This optimized method allows recovering of the grapevine apoplastic soluble proteins suitable for mono- and bi-dimensional gel electrophoresis for further proteomic analysis in order to elucidate their physiological functions. PMID- 27665563 TI - Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF). AB - Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue. PMID- 27665565 TI - Isolation of Exosome-Like Vesicles from Plants by Ultracentrifugation on Sucrose/Deuterium Oxide (D2O) Density Cushions. AB - Exosomes are nanovesicles of endocytic origin that are about 30-100 nm in diameter, surrounded by a lipid bilayer membrane, and contain proteins, nucleic acids, and other molecules. Mammalian cells- and biological fluids-derived exosomes have become the subject for a wide range of investigations in biological and biomedical sciences. More recently, a new interest is on the verge of rising: the presence of nanovesicles in plants. Lipoprotein vesicles from apoplastic fluid and exosome-like vesicles (ELVs) from fruit juice have been isolated and shown that they could be loaded with drugs and uptaken by recipient cells. In order to explore and analyze the contents and functions of ELVs, they must be isolated and purified with intense care. Isolation of ELVs can be a tedious process and often characterized by the co-purification of undesired contaminants. Here we describe a method which isolates ELVs based on their buoyant density. The method utilizes differential centrifugation in step 1 and 1 and 2 M sucrose/deuterium oxide double-cushion ultracentrifugation in step 2, to purify two diverse ELV subpopulations. In this method fruit juice is used as an example of starting material, although this protocol can be used for the isolation of vesicles from apoplastic fluid too. The quality and the quantity of ELV preparations have been found appropriate for downstream biological and structural studies, like proteomics, transcriptomics, and lipidomics. PMID- 27665566 TI - Long-lived nuclear spin states in rapidly rotating CH2D groups. AB - Although monodeuterated methyl groups support proton long-lived states, hindering of the methyl rotation limits the singlet relaxation time. We demonstrate an experimental case in which the rapid rotation of the CH2D group extends the singlet lifetime but does not quench the chemical shift difference between the CH2D protons, induced by the chiral environment. Proton singlet order is accessed using Spin-Lock Induced Crossing (SLIC) experiments, showing that the singlet relaxation time TS is over 2min, exceeding the longitudinal relaxation time T1 by a factor of more than 10. This result shows that proton singlet states may be accessible and long-lived in rapidly rotating CH2D groups. PMID- 27665567 TI - New psychoactive substances: an overview on recent publications on their toxicodynamics and toxicokinetics. AB - This review article covers English-written and PubMed-listed review articles and original studies published between January 2015 and April 2016 dealing with the toxicodynamics and toxicokinetics of new psychoactive substances. Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, NBOMes, phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on timely review articles followed by an overview and discussion on recent original studies. Both sections are then concluded by an opinion on these latest developments. This review shows that the NPS market is still highly dynamic and that the data published on their toxicodynamics and toxicokinetics can hardly keep pace with the appearance of new entities. However, data available are very helpful to understand and predict how NPS may behave in severe intoxication. The currently best-documented parameter is the in vitro metabolism of NPS, a prerequisite to allow detection of NPS in biological matrices in cases of acute intoxications or chronic consumption. However, additional data such as their chronic toxicity are still lacking. PMID- 27665568 TI - Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease. AB - The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD. PMID- 27665569 TI - Oxygen-Glucose Deprivation Induces G2/M Cell Cycle Arrest in Brain Pericytes Associated with ERK Inactivation. AB - Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry. The OGD treatment reduced the brain pericyte proliferation by causing G2/M phase arrest and downregulating the protein levels of cyclin D1, cyclin E, cdk4, and cyclin B1. Further studies demonstrated a simultaneous decrease in the activity of extracellular regulated protein kinases (ERK), suggesting a critical role of the ERK signaling cascade in the inhibition of OGD induced pericyte proliferation. We suggest that OGD inhibition of the proliferation of brain pericytes is associated with the inactivation of the ERK signaling pathway, which arrests them in the G2/M phase. PMID- 27665570 TI - Poliomyelitis in Ancient Egypt? PMID- 27665571 TI - Trichloroethylene (TCE) in tree cores to complement a subsurface investigation on residential property near a former electroplating facility. AB - Tree cores were collected and analyzed for trichloroethylene (TCE) on a private property between a former electroplating facility in Asheville, North Carolina (USA), and a contaminated wetland/spring complex. TCE was detected in 16 of 31 trees, the locations of which were largely consistent with a "plume core" delineated by a more detailed subsurface investigation nearly 2 years later. Concentrations in tree cores and nearby soil borings were not correlated, perhaps due to heterogeneities in both geologic and tree root structure, spatial and temporal variability in transpiration rates, or interferences caused by other contaminants at the site. Several tree cores without TCE provided evidence for significantly lower TCE concentrations in shallow groundwater along the margins of the contaminated spring complex in an area with limited accessibility. This study demonstrates that tree core analyses can complement a more extensive subsurface investigation, particularly in residential or ecologically sensitive areas. PMID- 27665572 TI - Evaluation of perfusion index as a tool for pain assessment in critically ill patients. AB - Pain is a common and undertreated problem in critically ill patients. Pain assessment in critically ill patients is challenging and relies on complex scoring systems. The aim of this work was to find out the possible role of the perfusion index (PI) measured by a pulse oximeter (Masimo Radical 7; Masimo Corp., Irvine, CA, USA) in pain assessment in critically ill patients. A prospective observational study was carried out on 87 sedated non-intubated patients in a surgical intensive care unit. In addition to routine monitoring, a Masimo pulse oximeter probe was used for PI measurement. The sedation level of the patients was assessed by using the Richmond Agitation-Sedation Scale (RASS). The pain intensity was determined by applying the behavioral pain scale for non intubated (BPS-NI) patients. The PI, arterial blood pressure, heart rate, RASS, and BPS-NI values before and after the application of a standard painful stimulus (changing the patient position) were reported. Correlation between the PI and other variables was carried out at the two measurements. Correlation between changes in the PI (delta PI) and in the hemodynamic variables, RASS, and BPS-NI was also done. Changing the patient position resulted in a significant increase in SBP (128 +/- 20 vs 120.4 +/- 20.6, P = 0.009), DBP (71.3 +/- 11.2 vs 68.7 +/- 11.3, P = 0.021), heart rate (99.5 +/- 19 vs 92.7 +/- 18.2, P = 0.013), and BPS NI (7[6-8] vs 3[3-3], P < 0.001) values and a significant decrease in the PI (1[0.5-1.9] vs 2.2[0.97-3.6], P < 0.001) value compared to the baseline readings. There was no correlation between the values of the PI and the ABP, BPS-NI, and RASS at the two measurements. A good correlation was found between the delta PI and delta BPS-NI (r = -0.616, P < 0.001). A weak correlation was observed between the PI and heart rate after the patient positioning (r = -0.249, P < 0.02). In surgical critically ill non-intubated patients, the application of a painful stimulus was associated with decreased PI. There was a good correlation between the change in the PI and the change in BPS-NI values after the application of painful stimulus. PMID- 27665574 TI - Clinical Pharmacokinetics and Pharmacodynamics of Safinamide. AB - The symptoms of Parkinson's disease (PD) reflect disruptions of a number of brain neurotransmitter systems of varying type and degree. Pharmacological agents with multiple neurochemical mechanisms of action are therefore promising candidates for countering these problems and providing comprehensive symptomatic relief for patients. The pharmacological profile of safinamide includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent Na+ channels, modulation of Ca2+ channels, and inhibition of glutamate release. Safinamide is administered once daily at oral doses of 50-100 mg; it is well-tolerated and safe. Clinical trials have found that it ameliorates motor symptoms when added to established levodopa or single dopamine receptor agonist therapy. The future role of safinamide in PD may be that it enables a reduction in the dosage of dopamine replacement therapies, thereby reducing the adverse effects associated with these treatments. The clinical convenience (once-daily administration), safety, and tolerability of safinamide are better than those of dopamine receptor agonists. The introduction of safinamide reflects a change of approach to drug development for anti-parkinsonian agents in that its broad spectrum of action corresponds to the multiple heterogeneous alterations of brain neurochemistry in PD, rather than being targeted at a single receptor type or neurochemical process. Safinamide is a promising new instrument for the effective symptomatic therapy of PD. PMID- 27665573 TI - Evaluation of Concomitant Antiretrovirals and CYP2C9/CYP2C19 Polymorphisms on the Pharmacokinetics of Etravirine. AB - BACKGROUND: Etravirine is a non-nucleoside reverse transcriptase inhibitor indicated in combination with other antiretrovirals for treatment-experienced HIV patients >=6 years of age. Etravirine is primarily metabolized by cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A. This analysis determined the impact of concomitant antiretrovirals and CYP2C9/CYP2C19 phenotype on the pharmacokinetics of etravirine. METHODS: We used 4728 plasma concentrations from 817 adult subjects collected from four clinical studies to develop the population pharmacokinetic model. The presence of atazanavir/ritonavir, lopinavir/ritonavir, darunavir/ritonavir, tenofovir disoproxil fumarate, or enfuvirtide together with the CYP2C9 and CYP2C19 phenotype and other demographics were evaluated. RESULTS: A one-compartment model with first-order input and a lag-time best described the data. Estimates of apparent total clearance (CL/F), apparent central volume of distribution (V c/F), first-order absorption rate constant (k a), and absorption lag-time were 41.7 L/h, 972 L, 1.16 h, and 1.32 h, respectively. Estimates of between-subject variability on CL/F, V c/F, and relative bioavailability (F) were 39.4 %CV (percentage coefficient of variation), 35.9 %CV and 35.5 %CV, respectively. Between-occasion variability on F was estimated to be 30.0 %CV. CL/F increased non-linearly with body weight and creatinine clearance (CLCR), and also varied based on CYP2C9/CYP2C19 phenotype. CONCLUSIONS: In this analysis, body weight, CLCR, and CYP2C9/CYP2C19 phenotype were found to describe some of the variability in CL/F. It was not possible to show an impact of concomitant antiretrovirals on the pharmacokinetics of etravirine for adults predominantly taking coadministered boosted protease inhibitors as a background antiretroviral regimen. PMID- 27665575 TI - Prevalence and clinical characteristics of insomnia and its subtypes in the Korean elderly. AB - BACKGROUND: Insomnia is known to be associated with psychiatric disorders, other sleep disorders and medical conditions, but the prevalence of insomnia diagnosis has never been estimated according to its subtypes. We studied the prevalence and clinical characteristics of insomnia diagnosis and its subtypes in the Korean elderly population. METHODS: Among 1423 sampled elderly individuals aged 60 years or older, 881 subjects participated in this study. The Athens Insomnia Scale was applied to detect insomnia symptoms, and insomnia diagnosis was finally evaluated using the international classification of sleep disorders, 2nd edition. To define insomnia subtypes, the DSM-IV-based interview, detailed history on sleep disorders and semi-structured interview for medical conditions were performed. Subsyndromal depression was defined when depressive symptoms did not meet the criteria for depressive disorders. RESULTS: The prevalence of insomnia disorder was 32.8% in all subjects, with the prevalence being significantly higher in women than in men (37.9% vs. 25.2%; p<0.001). The prevalence of insomnia subtypes was as follows; psychophysiological insomnia (PI), 20.5%; insomnia due to mental disorder 7.2%; insomnia due to general medical conditions 2.9%; insomnia in other sleep disorders 2.2%, and insomnia due to substance use 0.2%. Among subjects with PI, subsyndromal depression was diagnosed in 53.7%. CONCLUSIONS: Nearly one third of Korean elderly individuals suffer from insomnia and insomnia patients showed diverse comorbid conditions, especially depressive symptoms. By establishing insomnia subtypes, we can plan to treat comorbid conditions as well as insomnia itself. PMID- 27665577 TI - Urinary Catheterization: a Paradigm Shift in Difficult Urinary Catheterization. AB - BACKGROUND: The urinary catheter is an ancient device for urinary drainage in patients. Placement of a urethral catheter is a common medical procedure that may have led to morbidity and mortality. Urethral catheterization is commonly performed by a nurse. Difficult catheter placement generates urology consultation. Difficult catheterization with a vision-guided urinary catheter may provide expedited and successful catheter placement by nursing personnel. METHODS: A PubMed.gov and Ovid Medline search for articles on history of urinary catheter, difficult urinary catheterization, iatrogenic urethral injury, iatrogenic urethral injury and CAUTI, management of iatrogenic urethral injury, and techniques for urinary catheter placement was performed. RESULTS: The history of urinary catheters is reviewed. Technical advances in the last century are discussed. Indications for catheter placement are included. Outcomes and cost of complications of urinary catheters are discussed relative to present practice quality standards. Review of difficult urinary catheterization management algorithms developed with urological catheter improvements during the last decade is analyzed. Educational and technological advances to improve outcomes of urinary catheter use are addressed. CONCLUSIONS: Provider attention to issues of urinary catheterization is enhanced by education and additional skills for catheterization. Physician and nurse providers can use current technology with preparation to improve the catheterization care of patients. PMID- 27665576 TI - Lipoprotein lipase liberates free fatty acids to inhibit HCV infection and prevent hepatic lipid accumulation. AB - Lipoprotein lipase (LPL) has been identified as an anti-hepatitis C virus (HCV) host factor, but the cellular mechanism remains elusive. Here, we investigated the cellular mechanism of LPL involving in anti-HCV. The functional activation of peroxisome proliferator-activated receptor (PPAR) alpha signal by LPL transducing into hepatocytes was investigated in HCV-infected cells, primary human hepatocytes, and in HCV-core transgenic mice. The result showed that the levels of transcriptional transactivity and nuclear translocation of PPARalpha in Huh7 cells and primary human hepatocytes were elevated by physiologically ranged LPL treatment of either very-low density lipoprotein or HCV particles. The LPL induced hepatic PPARalpha activation was weakened by blocking the LPL enzymatic activity, and by preventing the cellular uptake of free unsaturated fatty acids with either albumin chelator or silencing of CD36 translocase. The knockdowns of PPARalpha and CD36 reversed the LPL-mediated suppression of HCV infection. Furthermore, treatment with LPL, like the direct activation of PPARalpha, not only reduced the levels of apolipoproteins B, E, and J, which are involved in assembly and release of HCV virions, but also alleviated hepatic lipid accumulation induced by core protein. HCV-core transgenic mice exhibited more hepatic miR-27b, which negatively regulates PPARalpha expression, than did the wild-type controls. The induction of LPL activity by fasting in the core transgenic mice activated PPARalpha downstream target genes that are involved in fatty acid beta-oxidation. Taken together, our study reveals dual beneficial outcomes of LPL in anti-HCV and anti-steatosis and shed light on the control of chronic hepatitis C in relation to LPL modulators. PMID- 27665578 TI - E-cigarettes and smoking cessation: a critique of a New England Journal Medicine commissioned case study. PMID- 27665580 TI - Diagnostic Value of Methylated Septin9 for Colorectal Cancer Screening: A Meta Analysis. AB - BACKGROUND Septin9 is a member of GTP-binding protein family, and is used as a predictive diagnostic index. However, it has not been widely adopted due to inconsistent results reported in the literature. The present study was performed to determine the diagnostic accuracy of methylated Septin9 (mSEPT9) for colorectal cancer (CRC) and to evaluate its utility in CRC screening. MATERIAL AND METHODS After reviewing relevant studies, accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratio [PLR/NLR], and diagnostic odds ratio [DOR]) were calculated for mSEPT9 in the diagnosis of CRC. Overall test performance was summarized using summary receiver operating characteristic curve analysis. Potential between-study heterogeneity was explored by use of a meta-regression model. We divided included studies into Epi proColon test and non-Epi proColon test subgroups. We compared the effects of mSEPT9 and fecal occult blood test (FOBT) for CRC screening. RESULTS A total of 9870 subjects in 14 studies were recruited. Pooled sensitivity and specificity, PLR, NLR, DOR, and corresponding 95% confidence intervals (CI) of mSEPT9 for CRC diagnosis were 0.66 (95% CI: 0.64-0.69), 0.91 (95% CI: 0.90-0.91), 5.59 (95% CI: 4.03-7.74), 0.37 (95% CI: 0.29-0.48), and 16.79 (95% CI: 10.54-26.76), respectively. The area under the summary ROC curve (AUC) was 0.8563. The AUCs in the Epi proColon test and non-Epi proColon test for CRC diagnosis were 0.8709 and 0.7968, respectively. In head-to-head comparison, AUC of mSEPT9 and FOBT for CRC diagnosis were 0.7857 and 0.6571, respectively. CONCLUSIONS The present study demonstrates that mSEPT9 can be a good diagnostic biomarker complementary to FOBT as a screening tool for CRC. PMID- 27665581 TI - Circulating CXCL16 in Diabetic Kidney Disease. AB - BACKGROUND/AIMS: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. METHODS: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR) categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. RESULTS: Plasma CXCL16 levels were 4.0+/-0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values) and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33+/-1.03 vs 3.88+/-0.86 ng/ml; p=0.013). In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. CONCLUSION: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels. PMID- 27665579 TI - Clinical outcomes in patients with acute hemodynamic collapse supported by extracorporeal life support. AB - Although extracorporeal life support (ECLS) is utilized for acute hemodynamic collapse, clinical outcomes for such patients are uncertain. The present study examined 30-day clinical outcomes in patients treated with ECLS for acute hemodynamic collapse, and determined the factors associated with 30-day mortality in patients who required ECLS for cardiopulmonary arrest (CPA). A total of 200 patients, in whom emergency ECLS was utilized for acute hemodynamic collapse from 2006 to 2015, were analyzed retrospectively. The impact of CPA on all-cause 30 day death in the overall population was examined by multivariable logistic regression analysis; comparisons were made between 30-day survivors (n = 78) and non-survivors (n = 122). In addition, clinical factors associated with 30-day survival for patients in whom ECLS was utilized for CPA (n = 139) were examined. All-cause 30-day mortality in the overall study population was 61 % (122/200). CPA was the most common cause of ECLS requirement (70 %), and the factor associated strongest with death at 30-days (OR 3.31, 95 % CI 1.75-6.36, P < 0.01). Witnessed CPA with bystander cardiopulmonary resuscitation (CPR) (OR 4.33, 95 % CI 1.08-29.1, P = 0.04) and a less than 40 min interval between CPA and ECLS (OR 3.49, 95 % CI 1.39-9.02, P < 0.01) were suggested as factors associated with 30-day survival in CPA patients. CPA as a trigger of ECLS was a strong contributor to 30-day death in patients in whom emergency ECLS was utilized. However, witnessed CPA with bystander CPR and a less than 40 min interval from CPA to start of ECLS were suggested as factors associated with survival in these CPA patients. PMID- 27665582 TI - Implementing Coping Power Adapted as a Universal Prevention Program in Italian Primary Schools: a Randomized Control Trial. AB - Behavioral problems in schools can cause serious harm to the emotional and social well-being of students and limit their ability to achieve their full academic potential. A prior pilot study on the universal application of Coping Power showed a significant decrease in the hyperactivity behaviors of five classes. The next step was to test whether Coping Power Universal could be successfully implemented by teachers in a variety of Italian schools. The sample involved 40 third- and fourth-grade classes (901 students) from public schools located in three Italian cities. Twenty classes were randomly assigned to Coping Power Universal, and 20 classes were randomly assigned to the control group, which received the strictly standard academic curriculum of Italian elementary schools. At each assessment period, the teachers completed the Strengths and Difficulties Questionnaire. The findings showed a significant reduction in hyperactive and inattention behaviors and conduct problems and emotional symptoms in the intervention classes compared with the control classes. This study suggests that Coping Power model can be delivered in school settings at both universal and targeted prevention levels and that in this multi-tiered prevention model, teachers can learn a set of intervention skills which can be delivered with flexibility, thus reducing some of the complexity and costs of schools using multiple interventions. PMID- 27665583 TI - Organic textile waste as a resource for sustainable agriculture in arid and semi arid areas. AB - New vegetation in barren areas offers possibilities for sequestering carbon in the soil. Arid and semi-arid areas (ASAs) are candidates for new vegetation. The possibility of agriculture in ASAs is reviewed, revealing the potential for cultivation by covering the surface with a layer of organic fibres. This layer collects more water from humidity in the air than does the uncovered mineral surface, and creates a humid environment that promotes microbial life. One possibility is to use large amounts of organic fibres for soil enhancement in ASAs. In the context of the European Commission Waste Framework Directive, the possibility of using textile waste from Sweden is explored. The costs for using Swedish textile waste are high, but possible gains are the sale of agricultural products and increased land prices as well as environmental mitigation. The findings suggest that field research on such agriculture in ASAs should start as soon as possible. PMID- 27665585 TI - Use of a prospective surveillance model to prevent breast cancer treatment related lymphedema: a single-center experience. AB - PURPOSE: Breast cancer patients undergoing axillary lymph node dissection (ALND) are at risk of lymphedema (LE). Successful management of LE relies on early diagnosis using sensitive modalities. In the current study, we explored the effectiveness of a surveillance program for lymphedema management (SLYM) compared to standard care. METHODS: Breast cancer patients who underwent ALND in Seoul National University Bundang Hospital from January 2008 to December 2015 were included in this prospective study. The SLYM commenced in May 2011. The LE outcomes of patients treated prior to initiation of the SLYM were compared with those of patients after SLYM implementation. RESULTS: A total of 707 patients were included, 390 in the SLYM group and 317 in the historical control (HC) group. A total of 203 patients (28.7 %) had episodes of all-stage LE during follow-up. Of these, 126 (19.7 %) were in the surveillance group and 77 (24.3 %) in the HC group. The overall 5-year cumulative incidence of LE (greater than stage 3) was 25 (95 % CI 15.4-34.6) (6.4 %) in the SLYM group and 48 (95 % CI, 15.4-34.6) (15.1 %) in the HC group. In the SLYM group, poor compliance had a significant impact on LE incidence (OR = 2.98, P = 0.002). Low level of self monitoring and insight scores were significantly related to LE incidence (OR = 1.31, P = 0.025) after adjusting for age, body mass index, the type of surgery chosen, radiation therapy, and chemotherapy. With a cut-off of 29.5 days from operation to the first visit to the LE clinic, the sensitivity was 60 % and the specificity 61 % in terms of predicting a LE event. CONCLUSIONS: Surveillance improves LE prevention compared to clinical evaluation. The first visit to the LE clinic should be made within 1 month after surgery. In the first year, visits should be made at intervals of less than 3 months. PMID- 27665586 TI - Breast cancer screening initiation after turning 40 years of age within the PROSPR consortium. AB - PURPOSE: Although United States clinical guidelines differ, the earliest recommended age for average risk breast cancer screening is 40 years. Little is known about factors influencing screening initiation. METHODS: We conducted a cohort study within the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We identified 3413 women on their 40th birthday in primary care networks at Geisel School of Medicine at Dartmouth (DH) and Brigham and Women's Hospital (BWH) during 2011-2013 with no prior breast imaging or breast cancer. Cumulative incidence curves and Cox modeling were used to determine time from the 40th birthday to first breast cancer screening, cohort exit, or 42nd birthday. We calculated hazards ratios and 95 % confidence intervals from multivariable Cox proportional hazards models. RESULTS: Breast cancer screening cumulative incidence by the 42nd birthday was 62.9 % (BWH) and 39.8 % (DH). Factors associated with screening initiation were: a primary care visit within a year (HR 4.99, 95 % CI 4.23-5.89), an increasing number of primary care visits within a year (p for trend <0.0001), ZIP code of residence annual median household income <=$52,000 (HR 0.79, 95 % CI 0.68-0.92), and health insurance type (Medicaid HR 0.72, 95 % CI 0.58-0.88; Medicare HR 0.55, 95 % CI 0.39-0.77; uninsured HR 0.37, 95 % CI 0.25-0.57). CONCLUSIONS: Breast cancer screening uptake after the 40th birthday varies by health system, primary care visits, median household income, and health insurance type, suggesting the need for further exploration. Future research should evaluate screening performance metrics after initiation and consider cumulative benefits and risks associated with breast cancer screening over time. PMID- 27665587 TI - Equivalent survival after nipple-sparing compared to non-nipple-sparing mastectomy: data from California, 1988-2013. AB - PURPOSE: Nipple-sparing mastectomy, which may improve cosmesis, body image, and sexual function in comparison to non-nipple-sparing mastectomy, is increasingly used to treat early-stage breast cancer; however, long-term survival data are lacking. We evaluated survival after nipple-sparing mastectomy versus non-nipple sparing mastectomy in a population-based cancer registry. METHODS: We conducted an observational study using the California Cancer Registry, considering all stage 0-III breast cancers diagnosed in California from 1988 to 2013. We compared breast cancer-specific and overall survival time after nipple-sparing versus non nipple-sparing mastectomy, using multivariable analysis. RESULTS: Among 157,592 stage 0-III female breast cancer patients treated with unilateral mastectomy from 1988-2013, 993 (0.6 %) were reported as having nipple-sparing and 156,599 (99.4 %) non-nipple-sparing mastectomies; median follow-up was 7.9 years. The proportion of mastectomies that were nipple-sparing increased over time (1988, 0.2 %; 2013, 5.1 %) and with neighborhood socioeconomic status, and decreased with age and stage. On multivariable analysis, nipple-sparing mastectomy was associated with a lower risk of breast cancer-specific mortality compared to non nipple-sparing mastectomy [hazard ratio (HR) 0.71, 95 % confidence interval (CI) 0.51-0.98]. However, when restricting to diagnoses 1996 or later and adjusting for a larger set of covariates, risk was attenuated (HR 0.86, 95 % CI 0.52-1.42). CONCLUSIONS: Among California breast cancer patients diagnosed from 1988-2013, nipple-sparing mastectomy was not associated with worse survival than non-nipple sparing mastectomy. These results may inform the decisions of patients and doctors deliberating between these surgical approaches for breast cancer treatment. PMID- 27665588 TI - Seronegative and occult hepatitis C virus infections in patients with hematological disorders. AB - Studies of the association between seronegative or occult (OCI) hepatitis C virus (HCV) infection, and hematological disorders have yielded controversial results. The aim of this study was to investigate seronegative and OCI HCV infections in among patients with different hematological disorders. This study included 90 anti-HCV-negative patients with either benign or malignant hematological disorders (group I), along with 20 age- and sex-matched apparently healthy subjects, who served as controls (group II). We tested for HCV RNA in sera and PBMCs by RT-nested PCR and for liver enzyme activity. Seronegativity and OCI were detected in 66.7 % and 20 % respectively, of the studied cases (group I). OCI was more evident in Hodgkin lymphoma and thalassemia. A significant increase in AST activity was observed in the seronegative and OCI groups and in ALT and AST in HCV-seronegative or OCI and negative HCV patients (p <= 0.05). Seronegativity and OCI are a significant clinical problem in patients with hematological disorders, warranting wider use of molecular tests combined with periodic evaluations of liver functions for diagnostic purposes. PMID- 27665589 TI - Crumple: An Efficient Tool to Explore Thoroughly the RNA Folding Landscape. AB - The folding landscape for an RNA sequence contains many diverse structures and motifs, which are often sampled rather than completely explored. Today's supercomputers make the complete enumeration of all possible folds for an RNA and a detailed description of the RNA folding landscape a more feasible task. This chapter provides protocols for using the Crumple folding algorithm, an efficient tool to generate all possible non-pseudoknotted folds for an RNA sequence. Crumple in conjunction with Sliding Windows and Assembly can incorporate experimental constraints on the global features of an RNA, such as the minimum number and lengths of helices, which may be determined by crystallography or cryo electron microscopy. This complete enumeration method is independent of free energy minimization and allows the user to incorporate experimental data such as chemical probing, SELEX data on RNA-protein binding motifs, and phylogenetic covariation. PMID- 27665590 TI - Secondary Structure Prediction of Single Sequences Using RNAstructure. AB - RNA secondary structure is often predicted using folding thermodynamics. RNAstructure is a software package that includes structure prediction by free energy minimization, prediction of base pairing probabilities, prediction of structures composed of highly probably base pairs, and prediction of structures with pseudoknots. A user-friendly graphical user interface is provided, and this interface works on Windows, Apple OS X, and Linux. This chapter provides protocols for using RNAstructure for structure prediction. PMID- 27665591 TI - Prediction of Secondary Structures Conserved in Multiple RNA Sequences. AB - RNA structure is conserved by evolution to a greater extent than sequence. Predicting the conserved structure for multiple homologous sequences can be much more accurate than predicting the structure for a single sequence. RNAstructure is a software package that includes the programs Dynalign, Multilign, TurboFold, and PARTS for predicting conserved RNA secondary structure. This chapter provides protocols for using these programs. PMID- 27665592 TI - Predicting RNA-RNA Interactions Using RNAstructure. AB - RNA-RNA binding is a required step for many regulatory and catalytic processes in the cell. Identifying RNA-RNA hybridization sites is challenging because of the competition between intramolecular and intermolecular structure formation. A complete picture of RNA-RNA binding includes an understanding of single-stranded folding and binding site accessibility, and is strongly concentration-dependent. This chapter provides guidance for using RNAstructure to predict RNA-RNA binding sites and RNA-RNA structures, utilizing free energy minimization and partition function calculations. RNAstructure is freely available at http://rna.urmc.rochester.edu/RNAstructure.html . PMID- 27665593 TI - A Method to Predict the Structure and Stability of RNA/RNA Complexes. AB - RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop-loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop-loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities. The method is based on the virtual bond RNA folding model (Vfold). The main emphasis in the method is placed on the evaluation of the entropy and free energy for the loops, especially tertiary kissing loops. The method also uses recursive partition function calculations and two-step screening algorithm for large, complicated structures of RNA/RNA complexes. As case studies, we use the HIV-1 Mal dimer and the siRNA/HIV-1 mutant (T4) to illustrate the method. PMID- 27665595 TI - Traditional Chemical Mapping of RNA Structure In Vitro and In Vivo. AB - Chemical probing is often used to gain knowledge on the secondary and tertiary structures of RNA molecules either free or engaged in complexes with ligands. The method monitors the reactivity of each nucleotide towards chemicals of various specificities reflecting the hydrogen bonding environment of each nucleotide within the RNA molecule. In addition, information can be obtained on the binding site of a ligand (noncoding RNAs, protein, metabolites), and on RNA conformational changes that accompanied ligand binding or perturbation of the environmental cues. The detection of the modifications can be obtained either by using end-labeled RNA molecules or by primer extension using reverse transcriptase. The goal of this chapter is to provide the reader with an experimental guide to probe the structure of RNA in vitro and in vivo with the most suitable chemical probes. PMID- 27665594 TI - STarMir Tools for Prediction of microRNA Binding Sites. AB - MicroRNAs (miRNAs) are a class of endogenous short noncoding RNAs that regulate gene expression by targeting messenger RNAs (mRNAs), which results in translational repression and/or mRNA degradation. As regulatory molecules, miRNAs are involved in many mammalian biological processes and also in the manifestation of certain human diseases. As miRNAs play central role in the regulation of gene expression, understanding miRNA-binding patterns is essential to gain an insight of miRNA mediated gene regulation and also holds promise for therapeutic applications. Computational prediction of miRNA binding sites on target mRNAs facilitates experimental investigation of miRNA functions. This chapter provides protocols for using the STarMir web server for improved predictions of miRNA binding sites on a target mRNA. As an application module of the Sfold RNA package, the current version of STarMir is an implementation of logistic prediction models developed with high-throughput miRNA binding data from cross linking immunoprecipitation (CLIP) studies. The models incorporated comprehensive thermodynamic, structural, and sequence features, and were found to make improved predictions of both seed and seedless sites, in comparison to the established algorithms (Liu et al., Nucleic Acids Res 41:e138, 2013). Their broad applicability was indicated by their good performance in cross-species validation. STarMir is freely available at http://sfold.wadsworth.org/starmir.html . PMID- 27665596 TI - High-Throughput Nuclease Probing of RNA Structures Using FragSeq. AB - High-throughput sequencing of cDNA (RNA-Seq) can be used to generate nuclease accessibility data for many distinct transcripts in the same mixture simultaneously. Such assays accelerate RNA structure analysis and provide researchers with new technologies to tackle biological questions on a transcriptome-wide scale. FragSeq is an experimental assay for transcriptome-wide RNA structure probing using RNA-Seq, coupled with data analysis tools that allow quantitative determination of nuclease accessibility at single-base resolution. We provide a practical guide to designing and carrying out FragSeq experiments and data analysis. PMID- 27665597 TI - Mapping RNA Structure In Vitro with SHAPE Chemistry and Next-Generation Sequencing (SHAPE-Seq). AB - Mapping RNA structure with selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistry has proven to be a versatile method for characterizing RNA structure in a variety of contexts. SHAPE reagents covalently modify RNAs in a structure-dependent manner to create adducts at the 2'-OH group of the ribose backbone at nucleotides that are structurally flexible. The positions of these adducts are detected using reverse transcriptase (RT) primer extension, which stops one nucleotide before the modification, to create a pool of cDNAs whose lengths reflect the location of SHAPE modification. Quantification of the cDNA pools is used to estimate the "reactivity" of each nucleotide in an RNA molecule to the SHAPE reagent. High reactivities indicate nucleotides that are structurally flexible, while low reactivities indicate nucleotides that are inflexible. These SHAPE reactivities can then be used to infer RNA structures by restraining RNA structure prediction algorithms. Here, we provide a state-of-the art protocol describing how to perform in vitro RNA structure probing with SHAPE chemistry using next-generation sequencing to quantify cDNA pools and estimate reactivities (SHAPE-Seq). The use of next-generation sequencing allows for higher throughput, more consistent data analysis, and multiplexing capabilities. The technique described herein, SHAPE-Seq v2.0, uses a universal reverse transcription priming site that is ligated to the RNA after SHAPE modification. The introduced priming site allows for the structural analysis of an RNA independent of its sequence. PMID- 27665598 TI - Experiment-Assisted Secondary Structure Prediction with RNAstructure. AB - Experimental probing data can be used to improve the accuracy of RNA secondary structure prediction. The software package RNAstructure can take advantage of enzymatic cleavage data, FMN cleavage data, traditional chemical modification reactivity data, and SHAPE reactivity data for secondary structure modeling. This chapter provides protocols for using experimental probing data with RNAstructure to restrain or constrain RNA secondary structure prediction. PMID- 27665599 TI - RNA Secondary Structure Determination by NMR. AB - Dynamic programming methods for predicting RNA secondary structure often use thermodynamics and experimental restraints and/or constraints to limit folding space. Chemical mapping results typically restrain certain nucleotides not to be in AU or GC pairs. Two-dimensional nuclear magnetic resonance (NMR) spectra can reveal the order of AU, GC, and GU pairs in double helixes. This chapter describes a program, NMR-assisted prediction of secondary structure and chemical shifts (NAPSS-CS), that constrains possible secondary structures on the basis of the NMR determined order and 5'-3' direction of AU, GC, and GU pairs in helixes. NAPSS-CS minimally requires input of the order of base pairs as determined from nuclear Overhauser effect spectroscopy (NOESY) of imino protons. The program deduces the 5'-3' direction of the base pairs if certain chemical shifts are also input. Secondary structures predicted by the program provide assignments of input chemical shifts to particular nucleotides in the sequence, thus facilitating an important step for determination of the three dimensional structure by NMR. The method is particularly useful for revealing pseudoknots and an example is provided. The method may also allow determination of secondary structures when a sequence folds into two structures that exchange slowly. PMID- 27665600 TI - Modeling Small Noncanonical RNA Motifs with the Rosetta FARFAR Server. AB - Noncanonical RNA motifs help define the vast complexity of RNA structure and function, and in many cases, these loops and junctions are on the order of only ten nucleotides in size. Unfortunately, despite their small size, there is no reliable method to determine the ensemble of lowest energy structures of junctions and loops at atomic accuracy. This chapter outlines straightforward protocols using a webserver for Rosetta Fragment Assembly of RNA with Full Atom Refinement (FARFAR) ( http://rosie.rosettacommons.org/rna_denovo/submit ) to model the 3D structure of small noncanonical RNA motifs for use in visualizing motifs and for further refinement or filtering with experimental data such as NMR chemical shifts. PMID- 27665601 TI - Automated RNA 3D Structure Prediction with RNAComposer. AB - RNAs adopt specific structures to perform their activities and these are critical to virtually all RNA-mediated processes. Because of difficulties in experimentally assessing structures of large RNAs using NMR, X-ray crystallography, or cryo-microscopy, there is currently great demand for new high resolution 3D structure prediction methods. Recently we reported on RNAComposer, a knowledge-based method for the fully automated RNA 3D structure prediction from a user-defined secondary structure. RNAComposer method is especially suited for structural biology users. Since our initial report in 2012, both servers, freely available at http://rnacomposer.ibch.poznan.pl and http://rnacomposer.cs.put.poznan.pl have been often visited. Therefore this chapter provides guidance for using RNAComposer and discusses points that should be considered when predicting 3D RNA structure. An application example presents current scope and limitations of RNAComposer. PMID- 27665602 TI - RNA 3D Structure Modeling by Combination of Template-Based Method ModeRNA, Template-Free Folding with SimRNA, and Refinement with QRNAS. AB - RNA encompasses an essential part of all known forms of life. The functions of many RNA molecules are dependent on their ability to form complex three dimensional (3D) structures. However, experimental determination of RNA 3D structures is laborious and challenging, and therefore, the majority of known RNAs remain structurally uncharacterized. To address this problem, computational structure prediction methods were developed that either utilize information derived from known structures of other RNA molecules (by way of template-based modeling) or attempt to simulate the physical process of RNA structure formation (by way of template-free modeling). All computational methods suffer from various limitations that make theoretical models less reliable than high-resolution experimentally determined structures. This chapter provides a protocol for computational modeling of RNA 3D structure that overcomes major limitations by combining two complementary approaches: template-based modeling that is capable of predicting global architectures based on similarity to other molecules but often fails to predict local unique features, and template-free modeling that can predict the local folding, but is limited to modeling the structure of relatively small molecules. Here, we combine the use of a template-based method ModeRNA with a template-free method SimRNA. ModeRNA requires a sequence alignment of the target RNA sequence to be modeled with a template of the known structure; it generates a model that predicts the structure of a conserved core and provides a starting point for modeling of variable regions. SimRNA can be used to fold small RNAs (<80 nt) without any additional structural information, and to refold parts of models for larger RNAs that have a correctly modeled core. ModeRNA can be either downloaded, compiled and run locally or run through a web interface at http://genesilico.pl/modernaserver/ . SimRNA is currently available to download for local use as a precompiled software package at http://genesilico.pl/software/stand-alone/simrna and as a web server at http://genesilico.pl/SimRNAweb . For model optimization we use QRNAS, available at http://genesilico.pl/qrnas . PMID- 27665603 TI - Exploring Alternative RNA Structure Sets Using MC-Flashfold and db2cm. AB - We created an accelerated version of MC-Fold called MC-Flashfold that allows us to compute large numbers of competing secondary structures including noncanonical base pairs. We visualize the base pairs in these sets using high quality intuitive dot plots and arc plots. Our new tools allow us to explore RNA dynamics by visualizing the competing structures in free energy bands. Here we describe how to use these tools to generate dot plots that reveal the postulated anti terminator stem in the E. coli trp operon leader sequence. These plots show the anti-terminator hairpin loop during transcription and as a minor population of the full-length leader sequence. This is a case of switching RNA structure that had been originally postulated based on short dyad inverted repeats. Other switching RNA sequences can be analyzed by using our method. PMID- 27665604 TI - NMR Methods for Characterization of RNA Secondary Structure. AB - Knowledge of RNA secondary structure is often sufficient to identify relationships between the structure of RNA and processing pathways, and the design of therapeutics. Nuclear magnetic resonance (NMR) can identify types of nucleotide base pairs and the sequence, thus limiting possible secondary structures. Because NMR experiments, like chemical mapping, are performed in solution, not in single crystals, experiments can be initiated as soon as the biomolecule is expressed and purified. This chapter summarizes NMR methods that permit rapid identification of RNA secondary structure, information that can be used as supplements to chemical mapping, and/or as preliminary steps required for 3D structure determination. The primary aim is to provide guidelines to enable a researcher with minimal knowledge of NMR to quickly extract secondary structure information from basic datasets. Instrumental and sample considerations that can maximize data quality are discussed along with some details for optimal data acquisition and processing parameters. Approaches for identifying base pair types in both unlabeled and isotopically labeled RNA are covered. Common problems, such as missing signals and overlaps, and approaches to address them are considered. Programs under development for merging NMR data with structure prediction algorithms are briefly discussed. PMID- 27665605 TI - The Quick and the Dead: A Guide to Fast Phasing of Small Ribozyme and Riboswitch Crystal Structures. AB - Ribozymes and riboswitches are examples of non-protein-coding (nc)RNA molecules that achieve biological activity by adopting complex three-dimensional folds. Visualization of such molecules at near-atomic resolution can enhance our understanding of how chemical groups are organized spatially, thereby providing novel insight into function. This approach has its challenges, which mainly entail sample crystallization followed by the application of empirical, structure determination methods that often include experimental "phasing" of X-ray diffraction data. A paucity of high-quality crystals or a low symmetry space group are factors that demand rapid assessment of phasing potential during an ongoing experiment in order to assure a successful outcome. Here we describe the process of evaluating the anomalous signal-to-noise as a prelude to single wavelength or multiwavelength anomalous diffraction (SAD or MAD) phasing. Test cases include an autolytic 62-mer RNA enzyme known as the hairpin ribozyme, and a 33-mer riboswitch that binds the modified guanine metabolite preQ1. The crystals were derivatized with iridium (III) hexammine and osmium (III) pentaammine triflate, respectively. Each data set was then subjected to the XPREP and SHELX programs to assess the anomalous signal-to-noise and to locate the heavy-atom substructure. Subsequent noise filtering was conducted in SHELXE or RESOLVE. The methods described are applicable to the rapid phasing of RNA X-ray diffraction data, and contrast the efficacy of in-house X-rays with those attainable from synchrotron-radiation sources in terms of the potential to plan for and execute an experimental structure determination. PMID- 27665606 TI - A reproducible protocol for neonatal ischemic injury and cardiac regeneration in neonatal mice. AB - Cardiac regeneration is one of the prime visions in cardiovascular research. The mouse neonatal apical resection and left anterior descending artery (LAD) ligation model introduced novel in vivo mammalian assays to study cardiac regeneration. However, recent reports and editorials discussed and critically questioned the value and technical reproducibility of the mouse neonatal myocardial infarction approach, making it paramount to develop and use a reproducible model system. We established a mouse neonatal myocardial infarction model by visually confirmed ligation of the LAD using microsurgery. TdT-mediated dUTP nick-end labeling (TUNEL) proved reproducible massive myocardial infarctions in a defined region of the apex and anterior wall of neonatal and 7-day-old mice. Whereas hearts ligated on postnatal day 7 displayed chronic injury, cardiac samples ligated immediately after birth always showed complete structural regeneration after long-term follow-up. Cardiac regeneration was observed in all mouse stains (C57BL/6J, ICR, and mixed background C57BL/6JxSv129) tested so far. We present a detailed in vivo protocol to study complex mechanisms of complete cardiac repair following ischemic cardiac damage. Neonatal LAD ligation surgery is feasible, and results in reproducible myocardial infarctions 24 h after ligation, and no structural myocardial defects are detectable following long-term follow-up. We encourage the cardiovascular community to use our protocol and teaching video to answer key scientific questions in the field of cardiac regeneration. PMID- 27665607 TI - Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats. AB - RATIONALE: Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats. METHODS: Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays. RESULTS: Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults. CONCLUSIONS: Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function. PMID- 27665608 TI - Rapid and simple determination of polyphyllin I, II, VI, and VII in different harvest times of cultivated Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz by UPLC-MS/MS and FT-IR. AB - Paris Polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz ("Dian Chonglou" in Chinese) is a famous herbal medicine in China, which is usually well known for activities of anti-cancer, hemolysis, and cytotoxicity. In this study, Fourier transform infrared (FT-IR) spectroscopy coupled with principal component analysis (PCA) and partial least-squares regression (PLSR) was applied to discriminate samples of P. polyphylla var. yunnanensis harvested in different years and determine the content of polyphyllin I, II, VI, and VII in P. polyphylla var. yunnanensis. Meanwhile, ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to study the dynamic changes of P. polyphylla var. yunnanensis harvested in different years (4, 5, 7, 8, 9, 12, and 13 years old). According to the UPLC-MS/MS result, the optimum harvest time of P. polyphylla var. yunnanensis is 8 years, due to the highest yield of four active components. By the PCA model, P. polyphylla var. yunnanensis could be exactly discriminated, except that two 8-year-old samples were misclassified as 9-year old samples. For the prediction of polyphyllin I, II, VI, and VII, the quantitative results are satisfactory, with a high value for the determination coefficient (R 2) and low values for the root-mean-square error of estimation (RMSEE), root-mean-square error of cross-validation (RMSECV), and root-mean square error of prediction (RMSEP). In conclusion, FT-IR combined with chemometrics is a promising method to accurately discriminate samples of P. polyphylla var. yunnanensis harvested in different years and determine the content of polyphyllin I, II, VI, and VII in P. polyphylla var. yunnanensis. PMID- 27665609 TI - Quantitative evaluation and discrimination of wild Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz from three regions of Yunnan Province using UHPLC-UV-MS and UV spectroscopy couple with partial least squares discriminant analysis. AB - Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz (PPY) is used widely as an anthelmintic, antimicrobial, and anti-tumor agent. Multiplicate analytical methods have been employed to discriminate PPY from different regions, as well as to identify regions most beneficial to the growing of this species. In this study, a convenient and accurate method was established using ultra high performance liquid chromatography (UHPLC) for simultaneous determination of four steroid saponins (Pa, Pb, polyphyllin VI, and chonglou saponin VII). Partial least squares discriminant analysis (PLS-DA) according to UHPLC and UV spectroscopy was applied to analyze 30 samples of PPY from three regions of Yunnan Province in China, and identify significant peaks. The results indicated that the correlation coefficients (r 2) of all calibration curves were above 0.999, and the inter- and intra-day relative standard deviations (RSD) of retention time and peak areas of common peaks were below 1.78 % and 3.40 %, respectively, with recovery rates of 99.6-103.4 % with RSD <=2 %. Quantitative analysis implied that the average values of total saponins in PPY from south Yunnan Province (19.9 mg/g) were higher than in the central (8.79 mg/g) district. Thus, further investigation could focus on the southern region to seek high quality PPY. The analysis found that PLS-DA for ultraviolet (UV) spectroscopy, which could separate the samples from three regions, was more appropriate than UHPLC. Retention times during 20-30.75 min of UHPLC, and absorption at 200-300 nm of the UV spectrum were identified as significant peaks for distinguishing PPY from different regions. PMID- 27665610 TI - Polymicrobial infections involving clinically relevant Gram-negative bacteria and fungi. AB - Interactions between fungi and bacteria and their relevance to human health and disease have recently attracted increased attention in biomedical fields. Emerging evidence shows that bacteria and fungi can have synergistic or antagonistic interactions, each with important implications for human colonization and disease. It is now appreciated that some of these interactions may be strategic and helps promote the survival of one or both microorganisms within the host. This review will shed light on clinically relevant interactions between fungi and Gram-negative bacteria. Mechanism of interaction, host immune responses, and preventive measures will also be reviewed. PMID- 27665611 TI - Evaluation of retinal ganglion cell-inner plexiform layer complex in healthy smokers. AB - PURPOSE: To evaluate the effect of smoking on ganglion cell complex and inner plexiform layer (GC-IPL) thickness measured by spectral domain optical coherence tomography (OCT). METHODS: The right eyes of 36 smoking (study group) and 36 never-smoking (control group) healthy subjects were included in this study. After full ophthalmologic examination, axial length measurement (AL), ganglion cell complex-inner plexiform layer (GC-IPL) thickness, retinal nerve fiber layer (RNFL) thickness, and central macular thickness (CMT) values were measured by OCT. Statistical analysis was performed to compare GC-IPL, RNFL thicknesses, and CMT values between groups. RESULTS: The mean age [mean +/- standard deviation (SD)] of 36 subjects in the study group was 26.2 +/- 6.0 years, and the mean age of 36 subjects in control group was 25.7 +/- 4.1 years. The mean ALs of the study group and the control group were 22.46 +/- 0.88 and 22.36 +/- 1.09 mm, respectively (p = 0.68). Mean GC-IPL thickness was 82.8 +/- 3 um in the study group and 84.3 +/- 3 um in the control group (p = 0.08). The mean RNFL values of study and control groups were 95. 8 +/- 7.9 and 97. 3 +/- 7.8 um, respectively (p = 0.39). The mean CMT values of study and control groups were 248.3 +/- 17.96 and 249.5 +/- 17.18 um, respectively (p = 0.78). CONCLUSION: Smoking does not seem to have any effect on GC-IPL thickness, mean RNFL and CMT values. Further studies in larger groups are needed to reveal the effect of smoking on these parameters. PMID- 27665612 TI - Pseudolentogenic astigmatic effect of multifocal intraocular lenses: non-corneal ocular residual astigmatism (N-CORA) as a new parameter in astigmatic change analysis. AB - PURPOSE: This study was initiated to introduce the term non-corneal ocular residual astigmatism (N-CORA) as a new parameter in astigmatic change analysis after implantation of two different types of non-toric, multifocal intraocular lenses (MIOL). METHODS: Seventy-two eyes from 72 consecutive patients after MIOL surgery were studied in terms of a retrospective, cross-sectional data analysis. Two types of spherical MIOL were used. Surgical technique in all patients was a 2.4-mm incision phacoemulsification, performed by one surgeon. To investigate the magnitude and axis of astigmatic changes, the true corneal astigmatism and Alpins vector method were applied. RESULTS: There were no statistically significant between-group differences related to the preoperative refraction or ocular residual astigmatism (ORA). After surgery, the mean refractive surgically induced astigmatism (RSIA) and the topographic SIA (TSIA) did not differ significantly between the lenses. The magnitude and orientation of ORA and N-CORA changed after surgery. CONCLUSIONS: There are no statistically significant differences in postoperative ORA in magnitude or axis when implanting different types of MIOL. The similarity of N-CORA between both MIOL types shows that both diffractive and refractive asymmetric MIOLs with plate haptics have the same pseudolentogenic astigmatic effect which could be presented in terms of the newly introduced parameter N-CORA. PMID- 27665614 TI - Symptoms of chronic rhinosinusitis differentially impact general health-related quality of life. AB - BACKGROUND: The degree to which different sinonasal symptoms contribute to the overall quality of life (QOL) detriment in chronic rhinosinusitis (CRS) patients remains unknown. In this study we sought to characterize the effect of different CRS symptoms on the general health-related QOL in patients. METHODOLOGY: We performed a prospective cross-sectional study of 131 adult patients with CRS. Sinonasal symptoms were evaluated using the 22-item Sinonasal Outcomes Test (SNOT 22) and general health-related QOL was evaluated using the EuroQol 5-Dimensional general health-related QOL survey (EQ5D) and visual analog scale (EQ5D-VAS). Health utility values (HUV) were determined using responses to the EQ5D. SNOT-22 scores were broken down into subdomain scores for sleep, nasal, otologic/facial pain and emotional function symptoms. RESULTS: The otologic/facial pain subdomain score consistently had the largest impact on EQ5D-VAS and HUV. After otologic/facial pain, the sleep subdomain score had the second largest effect while the nasal subdomain score had the least impact on general health-related QOL. CONCLUSIONS: Different types of CRS symptoms - most prominently otologic/facial pain and sleep-related symptoms - and their underlying pathophysiologic mechanisms may differentially affect the general health-related QOL detriment associated with CRS. These findings raise the possibility that treatment of the various symptoms associated with CRS may lead to differential improvement in general-health related QOL. PMID- 27665613 TI - The Active Space of Mexican Rice Borer Pheromone Traps. AB - The Mexican rice borer, Eoreuma loftini (Dyar) (Lepidoptera: Crambidae), is an invasive pest of sugarcane, Saccharum spp., rice, Oryza sativa L., and other graminaceous crops in the United States. Traps baited with the synthetic female sex pheromone of E. loftini are used for monitoring and management of this invasive pest. However, the active space, or radius of attraction, of these traps is not known. Two field experiments examined the effect of intertrap distance on trap captures with hexagonal arrays of traps deployed in rice stubble habitat in Texas (2011) and Louisiana (2013). Trap capture increased with increasing intertrap distance. Trap interference occurred at intertrap distances <=50 m in the 2011 experiment. Results from the experiment conducted in 2013 indicate that trap interference occurs at intertrap distances of 50 m, but not at distances >=100 m. These results suggest that under field conditions, E. loftini pheromone traps attract males from distances of 50-100 m. The active space of pheromone traps also was examined under controlled wind conditions by direct observation of male response to detection of the female sex pheromone. Eoreuma loftini males responded to the pheromone blend by becoming active, fanning their wings, and rapidly walking in circles. The mean distance from the pheromone source at which males responded was 47.6 m. This work provides the first documentation of active space for traps baited with female sex pheromone for a crambid species, and these data will improve pheromone trap deployment strategies for E. loftini monitoring and management. PMID- 27665615 TI - Incorporation of Viral Glycoprotein VSV-G Improves the Delivery of DNA by Erythrocyte Ghost into Cells Refractory to Conventional Transfection. AB - The objective of this study was to formulate a novel gene delivery system based on the erythrocyte ghost (EG) integrated with fusogenic viral glycoprotein vesicular stomatitis virus glycoprotein G (VSV-G). VSV-G proteins were harvested as condition medium of Ad293 cells carrying a VSV-G transgene and then incorporated into EG. Plasmid DNA was condensed by various transfection reagents. A luciferase expression construct (pGL3-control) and a DsRed expression cassette (pCMV-DsRed) were used to evaluate the delivery efficiency of DNA/EG/VSV-G complexes. VSV-G proteins could be incorporated into EG in static incubation under acidic conditions as evidenced by the Western blot analysis. Condensed plasmid DNA was bound mostly to the outer surface of EG, which could be detected by electromicroscopy and measured by electrophoresis. EG/VSV-G complexes stimulated the delivery of pGL3-control into Ad293 cells significantly with the luciferase activity increased about 4-fold as compared to that of the control. The delivery of pCMV-DsRed was also enhanced with the percentage of DsRed positive Ad293 cells increased from 55 % to about 80 %. Moreover, the transfection efficiency in 3T3, HeLa, INS-1, and bone marrow stem cell (BMSC) cells increased about 2-3-fold. Finally, confocal microscopy analysis showed that incorporation of VSV-G significantly enhanced the endocytosis of EG into target cells. In the present study, a novel type of non-viral DNA delivery vehicle consisting of EG and fusogenic VSV-G proteins was formulated, which showed superior transfection efficiency even in cells resistant to classical transfection. PMID- 27665616 TI - Farmers' Options to Address Water Scarcity in a Changing Climate: Case Studies from two Basins in Mediterranean Chile. AB - Irrigated agriculture in Mediterranean areas faces tremendous challenges because of its exposure to hydroclimatic variability, increasing competition for water from different sectors, and the possibility of a climatic change. In this context, efficient management of water resources emerges as a critical issue. This requires the adoption of technological innovations, investment in infrastructure, adequate institutional arrangements, and informed decision makers. To understand farmers' perceptions and their implementation of climate change adaptation strategies with regards to water management, primary information was captured in the Limari and Maule river basins in Chile. Farmers identified stressors for agriculture; climate change, droughts, and lack of water appeared as the most relevant stressors compared to others productive, economic, and institutional factors; revealing a rising relevance of climate related factors. While most producers perceived climate changes in recent years (92.9 %), a significant proportion (61.1 %) claim to have experienced drought, whereas only a fraction (31.9 %) have implemented a strategy to deal with this situation. Identified actions were classified in four groups: investments for water accumulation, modernization of irrigation systems, rationalization of water use, and partnership activities. Using a multinomial logit model these strategies were related to socioeconomic and productive characteristics. Results show that gender and farm size are relevant for investments, implementation and improvement of irrigation systems. For all the strategies described, access to weather information was a relevant element. The study provides empirical evidence of a recent increase in the importance assigned to climate factors by producers and adaptation options that can be supported by agricultural policy. PMID- 27665617 TI - Risk-Based Prioritization Method for the Classification of Groundwater Pollution from Hazardous Waste Landfills. AB - Hazardous waste landfill sites are a significant source of groundwater pollution. To ensure that these landfills with a significantly high risk of groundwater contamination are properly managed, a risk-based ranking method related to groundwater contamination is needed. In this research, a risk-based prioritization method for the classification of groundwater pollution from hazardous waste landfills was established. The method encompasses five phases, including risk pre-screening, indicator selection, characterization, classification and, lastly, validation. In the risk ranking index system employed here, 14 indicators involving hazardous waste landfills and migration in the vadose zone as well as aquifer were selected. The boundary of each indicator was determined by K-means cluster analysis and the weight of each indicator was calculated by principal component analysis. These methods were applied to 37 hazardous waste landfills in China. The result showed that the risk for groundwater contamination from hazardous waste landfills could be ranked into three classes from low to high risk. In all, 62.2 % of the hazardous waste landfill sites were classified in the low and medium risk classes. The process simulation method and standardized anomalies were used to validate the result of risk ranking; the results were consistent with the simulated results related to the characteristics of contamination. The risk ranking method was feasible, valid and can provide reference data related to risk management for groundwater contamination at hazardous waste landfill sites. PMID- 27665618 TI - The use of blocking screws with internal lengthening nail and reverse rule of thumb for blocking screws in limb lengthening and deformity correction surgery. AB - Internal lengthening nail (ILN) is a recent development in limb lengthening and deformity correction specialty. The ILN has the distinct advantage of combining acute deformity correction with gradual lengthening of bone. While using ILN, the short metaphyseal bone fragment may develop a deformity at the time of osteotomy and nail insertion or during bone lengthening because of the wide medullary canal. These deformities are typically predictable, and blocking screws (Poller screws) are helpful in these situations. This manuscript describes the common deformities that occur in femur and tibia with osteotomies at different locations while using ILN in antegrade and retrograde nailing technique. Also, a systematic approach to the appropriate use of blocking screws in these deformities is described. In addition, the "reverse rule of thumb" is introduced as a quick reference to determine the ideal location(s) and number of blocking screws. These principles are applicable to limb lengthening and deformity correction as well as fracture fixation using intramedullary nails. PMID- 27665619 TI - Expression of Cyt-c-Mediated Mitochondrial Apoptosis-Related Proteins in Rat Renal Proximal Tubules during Development. AB - BACKGROUND: Apoptosis regulates embryogenesis, organ metamorphosis and tissue homeostasis. Mitochondrial signaling is an apoptotic pathway, in which Cyt-c and Apaf-1 are transformed into an apoptosome, which activates procaspase-9 and triggers apoptosis. This study evaluated Cyt-c, Apaf-1 and caspase-9 expression during renal development. METHODS: Kidneys from embryonic (E) 16-, 18-, and 20 day-old fetuses and postnatal (P) 1-, 3-, 5-, 7-, 14-, and 21-day-old pups were obtained. Immunohistochemical analysis, dual-labeled immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique assay and Western blot were performed in addition to histological analysis. RESULTS: Immunohistochemistry showed that Cyt-c was strongly expressed in proximal and distal tubules (DTs) at all time points. Caspase-9 and Apaf-1 were strongly expressed in proximal tubules (PTs) but only weakly expressed in DTs. Dual-labeled immunofluorescence showed that most tubules expressed both Cyt-c and Apaf-1, except for some tubules that only expressed Cyt-c. The TUNEL assay showed a greater percentage of apoptotic cells in PTs compared to DTs. Apaf-1 and cleaved caspase-9 protein expression gradually increased during the embryonic period and peaked during the early postnatal period but apparently declined from P7. Cyt-c protein expression was weak during the embryonic period but obviously increased after P1. CONCLUSION: This study showed that PTs are more sensitive to apoptosis than DTs during rat renal development, even though both tubule segments contain a large number of mitochondria. Furthermore, Cyt-c-mediated mitochondrial apoptosis-related proteins play an important role in PTs during the early postnatal kidney development. PMID- 27665620 TI - Cholera, 2015. PMID- 27665621 TI - Dentin remineralization in acid challenge environment via PAMAM and calcium phosphate composite. AB - OBJECTIVES: The objective of this study was to investigate the effects of poly (amido amine) (PAMAM), composite with nanoparticles of amorphous calcium phosphate (NACP), and the combined PAMAM+NACP nanocomposite treatment, on remineralization of demineralized dentin in a cyclic artificial saliva/lactic acid environment for the first time. METHODS: Dentin specimens were prepared and demineralized with 37% phosphoric acid for 15s. Four groups were prepared: (1) dentin control, (2) dentin coated with PAMAM, (3) dentin with NACP composite, (4) dentin with PAMAM+NACP. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 21days. Acid neutralization and calcium (Ca) and phosphate (P) ion concentrations were measured. The remineralized dentin specimens were examined by scanning electron microscopy (SEM) and hardness testing. RESULTS: NACP nanocomposite had mechanical properties similar to commercial control composites (p>0.1). NACP composite had acid-neutralization and Ca and P ion release capability. PAMAM or NACP composite each alone achieved remineralization and increased the hardness of demineralized dentin (p<0.05). PAMAM+NACP nanocomposite achieved the greatest mineral regeneration in demineralized dentin and the greatest hardness increase in demineralized dentin, which approached the hardness of healthy dentin (p>0.1). SIGNIFICANCE: The superior remineralization efficacy of PAMAM+NACP was demonstrated for the first time. PAMAM+NACP induced remineralization in demineralized dentin in an acid challenge environment, when conventional remineralization methods such as PAMAM did not work well. The novel PAMAM+NACP composite approach is promising for a wide range of dental applications to inhibit caries and protect tooth structures. PMID- 27665622 TI - Impact of G12 Mutations on the Structure of K-Ras Probed by Ultraviolet Photodissociation Mass Spectrometry. AB - Single-residue mutations at Gly12 (G12X) in the GTP-ase protein K-Ras can lead to activation of different downstream signaling pathways, depending on the identity of the mutation, through a poorly defined mechanism. Herein, native mass spectrometry combined with top-down ultraviolet photodissociation (UVPD) was employed to investigate the structural changes occurring from G12X mutations of K Ras. Complexes between K-Ras or the G12X mutants and guanosine 5'-diphosphate (GDP) or GDPnP (a stable GTP analogue) were transferred to the gas phase by nano electrospray ionization and characterized using UVPD. Variations in the efficiencies of backbone cleavages were observed upon substitution of GDPnP for GDP as well as for the G12X mutants relative to wild-type K-Ras. An increase in the fragmentation efficiency in the segment containing the first 50 residues was observed for the K-Ras/GDPnP complexes relative to the K-Ras/GDP complexes, whereas a decrease in fragmentation efficiency occurred in the segment containing the last 100 residues. Within these general regions, the specific residues at which changes in fragmentation efficiency occurred correspond to the phosphate and guanine binding regions, respectively, and are indicative of a change in the binding motif upon replacement of the ligand (GDP versus GDPnP). Notably, unique changes in UVPD were observed for each G12X mutant with the cysteine and serine mutations exhibiting similar UVPD changes whereas the valine mutation was significantly different. These findings suggest a mechanism that links the identity of the G12X substitution to different downstream effects through long range conformational or dynamic effects as detected by variations in UVPD fragmentation. PMID- 27665623 TI - Defining the performance parameters of a rapid screening tool for myotonic dystrophy type 1 based on triplet-primed PCR and melt curve analysis. AB - BACKGROUND: DMPK CTG-repeat expansions that cause myotonic dystrophy type 1 (DM1) can be detected more rapidly, cost-effectively, and simply by combining triplet primed PCR (TP-PCR) with melting curve analysis (MCA). We undertook a detailed technical validation study to define the optimal operational parameters for performing bidirectional TP-PCR MCA assays. METHODS: We determined the assays' analytic specificity and sensitivity, assessed the effect of reaction volumes, DNA diluents, and common contaminants on melt peak temperature, determined the assays' sensitivity in detecting low-level mosaicism for repeat expansion, and evaluated their performance on two real-time PCR platforms. RESULTS: Both assays were highly specific and sensitive, and performed optimally under a broad range of parameters. Bidirectional TP-PCR MCA analysis also reduces the risk of generating false-negative results associated with the rare CCG-interruptions that may be present at either end of expanded alleles. CONCLUSION: The DMPK TP-PCR MCA is a highly specific, sensitive, and significantly cost-saving screening tool for DM1. PMID- 27665626 TI - ? AB - A medical team was on hand to care for world leaders during the G7 talks at Lancaster House last week. From left to right are: Gillian Spencer, Esmee Wakefield, Doctor Christine Lacy, Nursing Officer Andreas Kirkis and Matthew England. PMID- 27665625 TI - Educating trainers. AB - I once heard a conference speaker argue effectively against the use of the word 'train' in regard to nurse education. To train someone, she said, meant to pull, like dragging the unwilling through hoops to prove they had accomplished a particular task or set of tasks. Education, on the other hand, is about nurturing the student. It implies an ethos of learning, creativity and self- motivation. That's how nurses are prepared to take on their role in society. PMID- 27665624 TI - Th3[Th6(OH)4O4(H2O)6](SO4)12(H2O)13: A Self-Assembled Microporous Open-Framework Thorium Sulfate. AB - A neutral-framework thorium oxohydroxosulfate hydrate has been isolated from aqueous solution. This microporous structure, which self-assembles without a templating agent, is built from [Th6(OH)4O4(H2O)6]12+ hexamers and thorium(IV) monomers linked through bridging sulfates. Solution conditions were chosen to enable an active competition between sulfate and hydroxide for thorium coordination. Synthetic requirements are discussed for this rare example of a thorium(IV) polynuclear complex containing mixed oxo-, hydroxo-, and sulfato bridging moieties. PMID- 27665628 TI - UKCC to press ahead with its proposals. AB - The UKCC is to press ahead with its Post-registration Education and Practice (PREP) proposals after receiving overwhelming support from nurses in the public consultation. PMID- 27665627 TI - RCM conference. AB - Midwives do not need a separate Act to give them control of their own profession, the Commission on Midwifery Legislation, set up by the Royal College of Midwives last year, has concluded. PMID- 27665629 TI - Personnel Director gets greater powers. AB - The NHS Director of Personnel will have much greater responsibility for the management of nurse education under the Department of Health's new structure. PMID- 27665630 TI - ? AB - A blow for nursing: Royal College of Nursing General Secretary Christine Hancock, left, and President June Clark, blow out the candles on a seventy-fifth anniversary cake at the College's summer reception last week. PMID- 27665631 TI - Protecting educators who teach outside NHS. AB - The RCN may have to look for joint- membership agreements with other organisations to protect nurse educators moving from NHS colleges into local authority institutions, Council members were told last week. PMID- 27665633 TI - St Mary's Hospital. AB - Staff at St Mary's Hospital, Paddington, have voted against becoming an NHS Trust. PMID- 27665632 TI - Workforce planning for mental handicap nurses. AB - The UK's four chief nursing officers should carry out workforce planning exercises to identify the number of mental handicap nurses likely to be needed over the next ten years, according to a new report published last week. PMID- 27665634 TI - Appointment. AB - Judith Hill has been appointed Regional Nursing Director for Wessex. Ms Hill, who has been acting director since Jean Jarvis left in March, was previously regional nurse for clinical research and development. PMID- 27665636 TI - ? AB - Essex man: Singer David Essex opened the summer fete at the West Poplars elderly care unit in West London. PMID- 27665637 TI - Report predicts tough competition for patients. AB - Planning of health care in London following the second wave of hospital opt-outs in April 1992 will become a 'sick joke', with thousands of front-line jobs lost and health managers 'slugging it out' for each cash-backed patient, says a new report from the health union COHSE. PMID- 27665638 TI - New group for neurological patients at home. AB - People with chronic neurological illnesses who are being cared for at home could benefit from the new Continuing Care at Home Association (CONCAH) launched recently at the Kings' Fund, the organisers believe. The multidisciplinary group aims to improve community services for people with conditions such as Parkinson's disease or multiple sclerosis. PMID- 27665640 TI - ? AB - Midwife Isha Da Ramy-Kabia from Sierra Leone was presented with a land Rover by Scottish Health Minister Michael Forsyth in Edinburgh. PMID- 27665639 TI - First development unit to be set up in Scotland. AB - The UK's first midwifery development unit is to be set up in Scotland to promote excellence in practice, Scottish Health Minister Michael Forsyth announced at the Royal College of Midwives' annual conference. PMID- 27665641 TI - 'No proper consultation on educational changes'. AB - Midwives are up in arms against the English National Board's decision to replace specialist education officers with generalists. PMID- 27665643 TI - Sexuality in older people is overlooked in care. AB - Sexuality in older people is always overlooked when compiling care plans and nurses tend to deal with the issue extremely badly, Alex Henderson, locality manager with Hull Health Authority told psychiatric nurses last week. PMID- 27665642 TI - Parliament. AB - A Government-commissioned inquiry has found nurses are generally better trained than doctors for dealing with continence services. PMID- 27665644 TI - ? AB - The first Alun Islwyn Giles memorial nursing scholarship awards were presented to nine successful candidates at the Royal College of Nursing Welsh Board in Cardiff recently. Pictured left to right are: Board Secretary Anne Pegington; Robina Crocker; Eleri Wyn Williams; Kate Owens: Corinth Giles; Rosalind Shepherd; Alison Phillips; Angela McMellon and Board Chair Megan Edwards. PMID- 27665647 TI - Methods of dealing with ingested coins. AB - There is a lack of consensus on the management of swallowed coins in children but doctors from Birmingham and London suggest two techniques which might be useful in dislodging them from the mid and lower oesophagus. PMID- 27665646 TI - World news. AB - Europe Health reforms aimed at cutting costs are being introduced across Europe, a meeting organised by the European Health Policy Forum heard recently. Health professionals complain that there is little evidence to suggest the reforms will improve standards of care. PMID- 27665648 TI - Operating on legs in virtual reality. AB - Future surgeons may be able to practise leg operations without cutting into anything, thanks to an American invention. PMID- 27665649 TI - Salmonella enteritis, pancreatitis linked. AB - Patients with upper abdominal pain in salmonella enteritis should be investigated for concomitant pancreatitis, and in those with high amylase levels and diarrhoea, salmonella should be considered as a possible explanation. PMID- 27665650 TI - HIV tests may result in denial of treatment. AB - Perceived HIV status of infants may influence decisions on the treatment of unrelated conditions. PMID- 27665652 TI - Dynamics of change. AB - In June 1989 I moved to East Anglia to take up post as regional nurse with special responsibility for quality assurance, nursing standards and research after some years in post-basic education. At the time it seemed that nationally, the words 'standards' and 'quality' engendered negative feelings ranging from apathy to hostility among professional and support staff ( 1 ). PMID- 27665651 TI - Klebsiella-resisting cephalosporins. AB - The incidence of enterobacteriaceae with resistance to third generation cephalosporins may be underestimated, researchers say. PMID- 27665653 TI - Casualty in action. AB - No hospital drama has ever been complete without doctors playing centre stage. We've had Flying Doctors and Young Doctors, and Dr Kildare, not to mention numerous Carry on Doctors. Then came Angels, the drama series that put the spotlight firmly on nurses - unfortunately! PMID- 27665654 TI - Entering junior doctors' duties. AB - We take great pleasure in responding to Janice Devine's article on the opportunities afforded by the reduction in junior doctors' hours in the Points of View section (Nursing Standard July 10). PMID- 27665655 TI - Not stranded on the breach. AB - I was interested to read the article 'Nursing standards stranded' by Annie Chellel (Nursing Standard July 3). She aired many on the issues that standards have raised for nurses, but perhaps did not explain how the difficulties which standards might present could be turned into challenges and even opportunities. PMID- 27665656 TI - Information exchange. AB - The Royal College of Nursing has established a group to look at standards, nutrition and the older adult. The aim of the group is to devise national guidelines by a process of analysis and consensus in which standards set locally are compared with those written by the expert group. PMID- 27665657 TI - Ian Mansfield: loyal service. AB - Ian Mansfield, District Continence Adviser at Trafford Health Authority, died on 23 June 1991 in Hope Hospital, Salford. PMID- 27665658 TI - Wobbly status upsets levels. AB - With regard to Trevor Clay's suggestion about promoting second-level nurses to division one (Nursing Standard June 26). And why not? PMID- 27665659 TI - Keeping our own counsel. AB - With reference to the Grantham enquiry (Nursing Standard News, July 10) I applaud the Royal College of Nursing's efforts to provide counselling services for the nursing staff during the present difficulties. PMID- 27665660 TI - Points of View. AB - It has come to my attention that various departments are sending out memos to charge nurses starting off 'It has come to my attention that ...' and going on to detail some deficiency in nurses in complying with their systems. PMID- 27665661 TI - The elements of nursing, 3rd edition N Roper W Logan A Tierney Churchill Livingstone 362pp L15.95 0-443-03950-X [Formula: see text]. AB - Now in its third edition, the popular 'Roper, Logan & Tierney' can still be recommended to students pursuing studies for Part One of the Register. In both presentation and style, it's easy to read and has a logical pattern. Clearly, the authors know their audience exceptionally well. PMID- 27665662 TI - Vasectomy and Sterilization S Hayrnan Thorsons 106pp L3.99 0-7225-1654-1 [Formula: see text]. AB - The operation for sterilisation carries little physical or mental risk, but later regret at having taken that step can be devastating. Most important about using that method of contraception is making the decision in the first place; Suzie Hayman's aim is to provide information and stimulus for thought and discussion for people considering it. She writes specifically for the 'consumer'. PMID- 27665665 TI - Listings. PMID- 27665664 TI - Going for the juggler. AB - I am amused by the often-recited action plan, 'I'll stay at home while the kids are small but will return to nursing when they are settled at school.' PMID- 27665667 TI - Removal notice to "Sustained-release naltrexone for opioid dependence: A cochrane review and meta-analysis" [Drug Alcohol Depend. 146 (2015) e165-e166]. PMID- 27665666 TI - Report on the 17th Annual Land O'Lakes Bioanalytical Conference. AB - 17th Annual Land O'Lakes Bioanalytical Conference, Madison, WI, USA, 11-14 July 2016 The 17th Annual Land O'Lakes Bioanalytical Conference, titled 'Biomarker Validation, Stability, and Regulatory Concerns', was held on 11-14 July 2016 (Monday through Thursday) in Madison, WI, USA. The Land O'Lakes Conference is presented each year by the Division of Pharmacy Professional Development within the School of Pharmacy at the University of Wisconsin-Madison (USA). The purpose of this 3-day conference is to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference is designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis. To increase the interactive nature of the conference, the program is a mixture of lectures, interactive discussions and a poster session. This report summarizes the presentations at the 17th Annual Conference. PMID- 27665668 TI - Clinical Utility of the Envelope Task in Mild Cognitive Impairment and Dementia. AB - OBJECTIVE: Prospective memory (PM) is a cognitive function defined as the ability to perform an intention at an appropriate moment in the future. In the aging population, PM is essential for maintaining independent daily living. Introduced as a simple and quick way to assess PM in clinical settings, the envelope task has to date received very limited empirical and practical interest. METHODS: The present study investigated the task's clinical utility in detecting PM impairment in a sample composed of 49 healthy older adults (OA), 41 patients with Alzheimer's disease, and 64 individuals with amnestic and nonamnestic mild cognitive impairment (MCI) of heterogeneous etiology: 17 of idiopathic nature, 20 presenting an idiopathic rapid-eye movement sleep behaviour disorder, and 27 patients diagnosed with idiopathic Parkinson's disease. RESULTS: The envelope task was highly sensitive and specific in discriminating Alzheimer's disease patients from OA. Although it was specific in distinguishing MCI individuals from OA, its sensitivity was modest, especially in patients presenting a nonamnestic MCI subtype. CONCLUSIONS: Given its high specificity and simple low-cost administration procedure, the envelope task is a promising instrument for clinicians who seek to rapidly assess PM impairment in their daily practice. PMID- 27665669 TI - Twelve tips for applying the science of learning to health professions education. AB - Findings from the science of learning have clear implications for those responsible for teaching and curricular design. However, this data has been historically siloed from educators in practice, including those in health professions education. In this article, we aim to bring practical tips from the science of learning to health professions educators. We have chosen to organize the tips into six themes, highlighting strategies for 1) improving the processing of information, 2) promoting effortful learning for greater retention of knowledge over time, 3) applying learned information to new and varied contexts, 4) promoting the development of expertise, 5) harnessing the power of emotion for learning, and 6) teaching and learning in social contexts. We conclude with the importance of attending to metacognition in our learners and ourselves. Health professions education can be strengthened by incorporating these evidence-based techniques. PMID- 27665670 TI - Do we need [more] clinical trials in Transfusion Medicine and Hemotherapy? AB - This essay introduces a new series of papers to appear in Transfusion and Apheresis Sciences, to follow up clinical trials in the field of hemotherapy and transfusion medicine. This first paper stresses the weakness of such trials but also how difficult it is or may be to initiate clinical trials in this specialty. PMID- 27665671 TI - An exploratory study of barriers to inclusion in the European workplace. AB - BACKGROUND: The European Disability Strategy (2010-2020) seeks to significantly raise the proportion of people with disabilities working in the open labour market. The ERGO WORK project is a collaboration of academic and industrial partners in six European countries, focused on understanding and tackling barriers to workplace inclusion for workers with disabilities. METHODS: This study sought to explore the perceptions and needs of stakeholders in terms of workplace adaptation to the needs of employees with disabilities. An exploratory online survey was completed by 480 participants across six countries. RESULTS: The analysis suggests that workplaces could be further improved to meet the needs of employees with considerable scope for training within companies to raise awareness about employees' needs, employers' obligations and workplace adaptation. CONCLUSIONS: This snapshot suggests there is still a gap between intent and reality in workplace inclusion and further strategies are needed to improve the opportunities for employees with disabilities. The paper argues that ergonomics may have a key role to play in tackling these challenges and adapting the workplace environment and job design to suit the needs of individual employees. Implications for rehabilitation This study suggests there is considerable scope for workplace adaptation and improvements to meet the needs of employees with disabilities. Employers need and want further specialist practitioner guidance to facilitate workplace inclusion and support adaptation to individual needs. Organisations would benefit from training to raise awareness about potential solutions and approaches that would support more widespread employment of people with disabilities. PMID- 27665672 TI - Introduction of novel alpha1-hemoglobin gene mutation with transfusion-dependent phenotype. AB - OBJECTIVE AND IMPORTANCE: Thalassemia is the most frequently monogenetic disorders around the world that is inherited as a recessive single-gene disease, resulting from mutations in alpha- or beta-globin gene clusters. The aim of this report was to present a new insertional mutation in the alpha1 globin gene which causes transfusion-dependent anemia in alpha-thalassemic patients. CLINICAL PRESENTATION: Two 5-year-old girls with blood transfusion-dependent alpha thalassemia anemia and another girl with moderate alpha-thalassemia have been presented among patients who have been referred to Hematology and Thalassemia Research Center, Dastgheib Hospital, Shiraz, Iran. They were not relatives. All children were stunted and pale; they were put on regular blood transfusion every 14-21 days. INTERVENTION: Sequencing of the beta-globin gene was normal in all cases and their parents; but, alpha-globin gene sequencing results were remarkable. An insertion of 21 base pairs (IVS II+3ins (+21nt)(+GACCCGGTCAACTTCAAGGTG) in the alpha1-globin gene was detected in all three cases and one of their parents. In two cases, this insertion was accompanied by MED deletion and in one child by POLY A1 mutation. MED deletion was detected by gap-PCR. CONCLUSION: This new 21 base pair insertion cannot affect blood parameters on its own, but can present as continuous blood transfusion-dependent alpha-thalassemia. Thus, it is important to take this point into account for detecting the carriers, like beta-thalassemia carriers, which can present as transfusion-dependent children in parents with alpha-thalassemia trait. PMID- 27665673 TI - Impact of Reconstruction Algorithms and Gender-Associated Anatomy on Coronary Calcium Scoring with CT: An Anthropomorphic Phantom Study. AB - RATIONALE AND OBJECTIVES: Different computed tomography imaging protocols and patient characteristics can impact the accuracy and precision of the calcium score and may lead to inconsistent patient treatment recommendations. The aim of this work was to determine the impact of reconstruction algorithm and gender characteristics on coronary artery calcium scoring based on a phantom study using computed tomography. MATERIALS AND METHODS: Four synthetic heart vessels with vessel diameters corresponding to female and male left main and left circumflex arteries containing calcification-mimicking materials (200-1000 HU) were inserted into a thorax phantom and were scanned with and without female breast plates (male and female phantoms, respectively). Ten scans were acquired and were reconstructed at 3-mm slices using filtered-back projection (FBP) and iterative reconstruction with medium and strong denoising (IR3 and IR5) algorithms. Agatston and calcium volume scores were estimated for each vessel. Calcium scores for each vessel and the total calcium score (summation of all four vessels) were compared between the two phantoms to quantify the impact of the breast plates and reconstruction parameters. Calcium scores were also compared among vessels of different diameters to investigate the impact of the vessel size. RESULTS: The calcium scores were significantly larger for FBP reconstruction (FBP > IR3>IR5). Agatston scores (calcium volume score) for vessels in the male phantom scans were on average 4.8% (2.9%), 8.2% (7.1%), and 10.5% (9.4%) higher compared to those in the female phantom with FBP, IR3, and IR5, respectively, when exposure was conserved across phantoms. The total calcium scores from the male phantom were significantly larger than those from the female phantom (P <0.05). In general, calcium volume scores were underestimated (up to about 50%) for smaller vessels, especially when scanned in the female phantom. CONCLUSIONS: Calcium scores significantly decreased with iterative reconstruction and tended to be underestimated for female anatomy (smaller vessels and presence of breast plates). PMID- 27665674 TI - Antidiabetic activity of Chandraprabha vati - A classical Ayurvedic formulation. AB - BACKGROUND: Chandraprabha vati is a classical Ayurvedic formulation, markedly used for mitigation of Prameha, which correlates in many ways with obesity, metabolic syndrome and diabetes mellitus. OBJECTIVE: The present study was aimed to investigate effect of Chandraprabha vati in experimentally-induced hyperglycemia and lipid profile alterations. MATERIALS AND METHODS: Antidiabetic effect of Chandraprabha vati was studied in fifty five Wistar rats. Graded doses of Chandraprabha vati (50, 100 and 200 mg/kg) were administered orally for 7 days to normal and alloxan-hyperglycemic rats (65 mg/kg, intravenously), and to glucose loaded normal rats for oral glucose tolerance test (OGTT). Fasting plasma glucose levels were assessed on different time intervals along with plasma cholesterol and triglycerides. Metformin (500 mg/kg, orally) was used as standard drug. RESULTS: Chandraprabha vati did not cause any significant reduction in plasma glucose levels of normal rats (p > 0.05) but normalized the impaired glucose tolerance at 60 and 120 min (p < 0.05-p < 0.001) in OGTT when compared to vehicle control. In alloxan-hyperglycemic rats, administration of Chandraprabha vati (200 mg/kg) significantly reduced plasma glucose at 3 h, 12 h, 3rd day and 7th day (p < 0.01-p < 0.001) along with reduction in cholesterol and triglycerides levels (p < 0.01-p < 0.001) when compared to diabetic control group. The effects were comparable with metformin. CONCLUSIONS: Chandraprabha vati exhibited anti-hyperglycemic effect and attenuated alterations in lipid profile. The results support the use of Chandraprabha vati for correction of Prameha in clinical practice. PMID- 27665675 TI - Corrigendum to "A randomized trial of intensive outpatient (IOP) vs. standard outpatient (OP) buprenorphine treatment for African Americans" [Drug Alcohol Depend. 128 (2013) 222-229]. PMID- 27665676 TI - A cross-sectional observation on habitual non-alcoholic beverage consumption among adolescents from four Irish post-primary schools. AB - OBJECTIVE: No up-to-date data on the dietary intake of Irish adolescents are available. The aim of the present pilot study was to obtain and compare cross sectional information on habitual adolescent beverage consumption between four distinct post-primary schools in the Republic of Ireland, in 2014-2015. DESIGN: A cross-sectional observation study. A beverage consumption questionnaire was used to obtain data on beverage intake and influences on consumption. SETTING: Four post-primary mixed-sex schools in Ireland representing the following school classifications were selected for the study: urban fee-paying, urban disadvantaged, rural fee-paying and rural disadvantaged. SUBJECTS: Students (n 761) aged 12-18 years. RESULTS: Data were analysed by Kruskal-Wallis (non parametric) ANOVA to compare the distribution of beverage consumption across the schools. Water was the most highly consumed beverage among students from all four schools (median 1425 ml/d). Students from urban and rural disadvantaged schools reported a significantly higher volume of carbonated beverage intake than students from fee-paying schools. Students from an urban disadvantaged school also reported a significantly higher volume of carbonated beverage and energy drink intake compared with the other three schools. Students from an urban fee paying school reported the highest consumption of water, while rural disadvantaged school students were the biggest consumers of tea and milk. CONCLUSIONS: Significant differences in beverage consumption (ml/d) were reported by adolescents from four schools in Ireland. Surveillance on current beverage consumption trends among adolescents is vital to guide policies and interventions, and for appropriate targeting of resources. PMID- 27665678 TI - Intrinsic protein fluorescence assays for GEF, GAP and post-translational modifications of small GTPases. AB - Evidence and arguments are summarized that suggest that intrinsic (tryptophan) protein fluorescence provides an excellent and convenient signal for monitoring both GEF (guanine nucleotide exchange factor) and GAP (GTPase activating protein) activity of a large number of small GTPases. In addition, post-translational modifications of Rab proteins occurring in a region known to be a hot spot for such modifications also lead to fluorescence changes that can be accurately monitored in a time-dependent manner. It is suggested that intrinsic fluorescence should be the first method chosen for monitoring such reactions of tryptophan containing small GTPases. PMID- 27665677 TI - Metabolic tracing of monoacylglycerol acyltransferase-2 activity in vitro and in vivo. AB - Monoacylglycerol acyltransferase 2 (MGAT2) catalyzes the synthesis of diacylglycerol (DAG) from free fatty acids (FFA) and sn-monoacylglycerol (MG), the two major hydrolysis products of dietary fat. To demonstrate MGAT2-mediated cellular activity of triglyceride (TG) synthesis, we utilized 1-oleoyl-glycerol d5 as a substrate to trace MGAT2-driven 1-oleoyl-glycerol-d5 incorporation into TG in HEK293 cells stably expressing human MGAT2. The oleoyl-glycerol-d5 incorporated major TG species were then quantified by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) in a 96-well format. Conventional MGAT2 target-engagement in vivo assays measure the elevation of total plasma TG by orally dosing a bolus of TG oil. We developed a novel LC/ESI/MS/MS-based fat absorption assay to assess the ability of MGAT2 inhibitors to inhibit fat absorption in CD1 mice by a meal tolerance test consisting of a mixture of liquid Boost plus(r) and 0.59 g/kg U13C-TG oil. The newly resynthesized plasma heavy TGs containing three 13C in the glycerol backbone and two U13C-acyl-chains, which represented the digested, absorbed and resynthesized TGs, were then quantitated by LC/ESI/MS/MS. With this assay, we identified a potent MGAT2 inhibitor that blocked MGAT2-mediated activity in vitro and in vivo. The use of 1-oleoyl-glycerol-d5 and U13C-TG oil followed by LC/ESI/MS/MS detection of stable-isotopic labeled DAG, TG, or glycerol provides a wide range of applications to study pathophysiological regulation of the monoacylglycerol pathway and MGAT2 activity. PMID- 27665679 TI - Hyperpolarized MRS: New tool to study real-time brain function and metabolism. AB - The advent of dissolution dynamic nuclear polarization (DNP) led to the emergence of a new kind of magnetic resonance (MR) measurements providing the opportunity to probe metabolism in vivo in real time. It has been shown that, following the injection of hyperpolarized substrates prepared using dissolution DNP, specific metabolic bioprobes that can be used to differentiate between healthy and pathological tissue in preclinical and clinical studies can be readily detected by MR thanks to the tremendous signal enhancement. The present article aims at reviewing the studies of cerebral function and metabolism based on the use of hyperpolarized MR. The constraints and future opportunities that this technology could offer are discussed. PMID- 27665680 TI - A switching control law approach for cancer immunotherapy of an evolutionary tumor growth model. AB - We propose a new approach for tumor immunotherapy which is based on a switching control strategy defined on domains of attraction of equilibria of interest. For this, we consider a recently derived model which captures the effects of the tumor cells on the immune system and viceversa, through predator-prey competition terms. Additionally, it incorporates the immune system's mechanism for producing hunting immune cells, which makes the model suitable for immunotherapy strategies analysis and design. For computing domains of attraction for the tumor nonlinear dynamics, and thus, for deriving immunotherapeutic strategies we employ rational Lyapunov functions. Finally, we apply the switching control strategy to destabilize an invasive tumor equilibrium and steer the system trajectories to tumor dormancy. PMID- 27665682 TI - The biosynthesis of brassicicolin A in the phytopathogen Alternaria brassicicola. AB - Alternaria brassicicola (Schwein.) Wiltshire is a phytopathogenic fungus that together with A. brassicae causes Alternaria black spot disease in Brassica species. Brassicicolin A is the major host-selective phytotoxin produced in cultures of A. brassicicola. Biosynthetic studies to establish the metabolic precursors of brassicicolin A were carried out with isotopically labeled compounds. Incorporation of D-[13C6]glucose, L-[15N]valine, or L-[2H8]valine into brassicicolin A was established using 1H, 13C, 15N NMR and INADEQUATE spectroscopy and HPLC-ESI-MS spectrometry. Based on analyses of the spectroscopic data, the labeling patterns of brassicicolin A isolated from cultures incubated with the labeled precursors are found to be consistent with both the glycolytic and the valine pathways. That is, the carbons of mannitol and acetyl units and the isocyanide carbon atoms are derived from D-[13C6]glucose whereas the hydroxyisopentanoyl and isocyanoisopentanoyl units are derived from L-valine, including the nitrogen atoms of both isocyanide groups. PMID- 27665681 TI - Modeling antimicrobial tolerance and treatment of heterogeneous biofilms. AB - A multiphasic, hydrodynamic model for spatially heterogeneous biofilms based on the phase field formulation is developed and applied to analyze antimicrobial tolerance of biofilms by acknowledging the existence of persistent and susceptible cells in the total population of bacteria. The model implements a new conversion rate between persistent and susceptible cells and its homogeneous dynamics is bench-marked against a known experiment quantitatively. It is then discretized and solved on graphic processing units (GPUs) in 3-D space and time. With the model, biofilm development and antimicrobial treatment of biofilms in a flow cell are investigated numerically. Model predictions agree qualitatively well with available experimental observations. Specifically, numerical results demonstrate that: (i) in a flow cell, nutrient, diffused in solvent and transported by hydrodynamics, has an apparent impact on persister formation, thereby antimicrobial persistence of biofilms; (ii) dosing antimicrobial agents inside biofilms is more effective than dosing through diffusion in solvent; (iii) periodic dosing is less effective in antimicrobial treatment of biofilms in a nutrient deficient environment than in a nutrient sufficient environment. This model provides us with a simulation tool to analyze mechanisms of biofilm tolerance to antimicrobial agents and to derive potentially optimal dosing strategies for biofilm control and treatment. PMID- 27665683 TI - Corrigendum to "Design of the NIDA clinical trials network validation study of tobacco, alcohol, prescription medications, and substance use/misuse (TAPS) tool" [Contemporary Clinical Trials. 2016 Jul. 19; 50: 90-97]. PMID- 27665684 TI - Cerebellar volume change in response to electroconvulsive therapy in patients with major depression. AB - Electroconvulsive therapy (ECT) is remarkably effective in severe major depressive disorder (MDD). Growing evidence has accumulated for brain structural and functional changes in response to ECT, primarily within cortico-limbic regions that have been considered in current neurobiological models of MDD. Despite increasing evidence for important cerebellar contributions to affective, cognitive and attentional processes, investigations on cerebellar effects of ECT in depression are yet lacking. In this study, using cerebellum-optimized voxel based analysis methods, we investigated cerebellar volume in 12 MDD patients who received right-sided unilateral ECT. 16 healthy controls (HC) were included. Structural MRI data was acquired before and after ECT and controls were scanned once. Baseline structural differences in MDD compared to HC were located within the "cognitive cerebellum" and remained unchanged with intervention. ECT led to gray matter volume increase of left cerebellar area VIIa crus I, a region ascribed to the "affective/limbic cerebellum". The effects of ECT on cerebellar structure correlated with overall symptom relief. These findings provide preliminary evidence that structural change of the cerebellum in response to ECT may be related to the treatment's antidepressant effects. PMID- 27665685 TI - Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population. AB - BACKGROUND Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. More advanced work is required in the detection of biomarkers for CRC susceptibility and prognosis. High-mobility group box-1 (HMGB1) is an angiogenesis-related gene reported to be associated with the development of CRC. The direct evidence of HMGB1 gene polymorphisms as biomarkers for CRC has not been reported previously. MATERIAL AND METHODS A total of 240 CRC patients and 480 healthy controls were periodically enrolled. DNA was extracted from blood specimens. The distributions of SNPs of HMGB1 were determined by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS In this case-control study, we observed a significant association between overall CRC risk and SNP rs2249825 (CG vs. CC and GG vs. CC). Participants carrying both rs2249825 CG (OR, 2.67; 95% CI, 1.89 to 3.78) and rs2249825 GG genotypes (OR, 2.32; 95% CI, 1.13 to 4.73) had a significantly increased risk of developing CRC compared to those carrying GG genotype. rs2249825 was associated with the risk of CRC in the dominant model but not in the recessive model. However, we found no significant differences in the rs1412125 or rs1045411 polymorphisms in the HMGB1. Advanced analyses showed that the number of rs2249825 G alleles showed a significant relationship with risk of CRC. CONCLUSIONS Our results show an association between HMGB1 rs2249825 SNP and CRC incidence in the Chinese Han population. However, population-based studies with more subjects and prognostic effects are needed to verify the association of HMGB1 SNPs with CRC susceptibility, severity, and long-term prognosis. PMID- 27665686 TI - 16th International Medical Geography Symposium special collection: A current snapshot of health geography. PMID- 27665687 TI - [Drugs news]. PMID- 27665689 TI - Commentary on 'Ordering, metastability and phase transitions in two-dimensional systems' J M Kosterlitz and D J Thouless (1973 J. Phys. C: Solid State Phys. 6 1181-203)-the early basis of the successful Kosterlitz-Thouless theory. PMID- 27665688 TI - Local allergic rhinitis. PMID- 27665691 TI - Antimicrobial Susceptibility of Microorganisms Isolated from Periapical Periodontitis Lesions. AB - Periapical periodontitis usually results from microbial infection, with these microorganisms occasionally migrating to the root canal, which can lead to further, potentially life-threatening, complications. Here, the susceptibility of 27 bacterial strains to various antimicrobial agents was evaluated. These strains comprised 13 species; 16 of the strains were clinical isolates from periapical lesions. Each strain was inoculated onto blood agar plates containing one of the antimicrobial agents. The plates were incubated anaerobically at 37 degrees C for 96 hr and the minimal inhibitory concentrations (MICs) determined. Ten strains required an MIC of 32 MUg/ml or greater for amoxicillin, 6 for cefmetazole, and 5 for cefcapene among beta-lactam antibiotics; 8 strains required an MIC of 32 MUg/ml or greater for clindamycin, 4 for azithromycin, and 11 for clarithromycin among macrolide antibiotics; 3 strains required an MIC of 32 MUg/ml or greater for ciprofloxacin and 2 for ofloxacin among fluoroquinolones. The effect of cefcapene on 5 strains was evaluated after biofilm formation to investigate the relationship between biofilm formation and susceptibility. All strains showed a decrease in susceptibility after biofilm formation. The results revealed that several antimicrobial agents commonly used in a clinical setting, including amoxicillin, cefmetazole, and clindamycin, are potentially effective in the treatment of orofacial odontogenic infections. The development of resistant strains, however, means that this can no longer be guaranteed. In addition, azithromycin, ciprofloxacin, and ofloxacin were more effective than the 3 beta lactam antibiotics tested. These results suggest that sensitivity testing is needed if odontogenic infections are to be treated safely and effectively. PMID- 27665690 TI - Lymphangiogenesis and NOS Localization in Healing Process after Tooth Extraction in Akita Mouse. AB - Type I diabetes, an autoimmune disease, induces insulin deficiency, which then disrupts vascular endothelial cell function, affecting blood and lymphatic vessels. Nitric oxide (NO) is an immune-induced destructive mediator in type I diabetes, and inhibition of its production promotes arteriosclerosis. In this study, lymphangiogenesis and expression of NO synthase (NOS) during the healing process after tooth extraction were investigated immunohistochemically in control (C57BL) and Akita mice as a diabetes model. Between 1, 4, and 10 days after extraction, expression of NOS, vascular endothelial growth factor-C (VEGF-C), VEGF receptor-3 (VEGFR-3), and von Willebrand factor was strongest during the granulation tissue phase. This suggests that severe inflammation triggers regulation of NOS and these other angiogenic and lymphangiogenic factors. During the callus phase, a few days after extraction, induced osteoblasts were positive for VEGF-C and VEGFR-3 in both the control and Akita mice, suggesting that bone formation is active in this period. Bone formation in the Akita group exceeded that in the controls. Bone tissue formation was disrupted under hyperglycemic conditions, however, suggesting that such activity would be insufficient to produce new bone. PMID- 27665692 TI - Influence of Lifestyle Factors on Risk of Dental Caries among Children Living in Urban China. AB - The prevalence of dental caries has been decreasing among kindergarten children in Shanghai, China, over recent years, although it still remains at an unacceptably high level. The purpose of this study was to identify which factors were important in providing oral health guidance and achieving further improvement in the oral health status of kindergarten children in urban China. A survey was conducted on dental caries in 128 Japanese and 368 Chinese kindergarten children and a questionnaire given to their parents/guardians on each child's lifestyle and dietary habits from birth to the present. Correlations between responses to each questionnaire item and the status of dental caries were statistically analyzed. The dft index score (p=0.0016), prevalence of dental caries (p=0.0002), and percentages of children with decayed (untreated caries affected) teeth (p<0.0001) were significantly higher in the Chinese than in the Japanese children. Many differences were observed in lifestyle factors between the two groups. The percentage of parents failing to control the child's snacking habits between meals was higher in China, and weaning was significantly delayed in China compared with in Japan. These lifestyle factors were considered to be associated closely with the high risk of dental caries in Chinese kindergarten children. These findings indicate that oral health guidance for kindergarten children in Shanghai, China, should focus on control of dietary habits, including control of inter-meal snacking, and breastfeeding practices. The results of this study may help improve the status of dental caries among Chinese children. PMID- 27665693 TI - Relationship between Orthodontic Treatment Plan and Goslon Yardstick Assessment in Japanese Patients with Unilateral Cleft Lip and Palate: One-stage vs. Two stage Palatoplasty. AB - The present study targeted patients with unilateral cleft lip and palate (UCLP) undergoing either one - (Wardill technique) or two-stage palatoplasty (Perko technique). Correlations between Goslon Yardstick scores and orthodontic appliances used and whether an osteotomy was performed were investigated. No differences were observed between the two types of palatoplasty in terms of Goslon Yardstick scores. A palatal expander and protraction facemask were used in Phase I of orthodontic treatment. The palatal expander was selected for most patients with UCLP in Phase I, regardless of the surgical technique used. A protraction facemask was used in patients undergoing the Wardill procedure who had a Goslon Yardstick score placing them in Group 3 or 4. In contrast, a protraction facemask was used in patients undergoing the Perko procedure who had a Goslon Yardstick score placing them in Group 4. No significant differences were observed in the Goslon Yardstick scores yielded by either type of procedure. The Goslon Yardstick score in relation to whether an osteotomy was performed in Phase II as part of orthodontic treatment was determined, focusing on the relationship between that score and the palatoplasty method used. A protraction facemask was used in patients undergoing the Perko procedure, which eliminated the need for an osteotomy at a future date. However, a protraction facemask was also used in patients undergoing the Wardill option, and those patients were likely to require an osteotomy. In other words, the results suggest that the type of palatoplasty selected will determine the effectiveness of any orthodontic appliances used. PMID- 27665694 TI - Propofol-remifentanil is More Effective than Propofol-fentanyl in Decreasing Intraoperative Blood Loss during Sagittal Split Ramus Osteotomy. AB - This study retrospectively compared blood loss during sagittal split ramus osteotomy in patients receiving propofol-remifentanil (R group) and those receiving propofol-fentanyl (F group). All patients underwent sagittal split ramus osteotomy under general anesthesia during the 3-year 4-month period between October 2007 and February 2011 in an operating room at Tokyo Dental College Suidobashi Hospital. Blood loss in the R group was significantly less than that in the F group. Mean arterial pressure and heart rate, measured at 20 and 15 min after tracheal intubation, respectively, were both lower in the R group. No marked change was observed in blood pressure in the R group under general anesthesia, however. Volume of urine was also larger in the R group. The results of this study suggest that remifentanil is effective in reducing intraoperative blood loss during sagittal split ramus osteotomy. PMID- 27665695 TI - Relationship between Obstructive Sleep Apnea and Self-assessed Oral Health Status: An Internet Survey. AB - The purpose of this study based on a cross-sectional internet survey was to investigate the relationship between risk of obstructive sleep apnea (OSA) and self-assessed oral health status. The participants, who comprised individuals registered with an online research company, were required to complete a self reported questionnaire. Those answering in the affirmative to both of the following two questions were placed in the OSA-risk group, while those answering in the negative were assigned to the control group: 'Have other people noticed pauses in your breathing while you are sleeping?' and 'Do you feel excessively sleepy during the daytime?'. A total of 493 were included in the OSA-risk group and 2,560 in the control group. Among the total 3,053 respondents, the highest prevalence for OSA risk in men was in the 50-59-year age range, although this tended to level off after age 60 years. No such trend was observed in women, however. Multiple logistic regression analysis was performed to identify the relationship between risk of OSA and self-assessed oral health status. Significant correlations were observed with the following parameters: difficulty in opening mouth (odds ratio [OR]: 2.66; 95% confidence interval [CI]: 1.647 4.311), dry mouth (OR: 2.11; CI: 1.544-2.876), bad breath (OR: 1.69; CI: 1.309 2.186), gingival bleeding (OR: 1.48; CI: 1.134-1.932), and gingival swelling (OR: 1.44; CI: 1.046-1.981). These results suggest a relationship between risk of OSA and self-assessed oral health status, indicating that treating OSA might improve oral health status. Further study is needed to demonstrate a causal relationship between OSA and self-assessed oral health status, however. PMID- 27665696 TI - Cutaneous Sinus Tract from Mandibular Second Molar with C-shaped Canal System and Improper Former Root Canal Treatment: A Case Report. AB - Here, we report the diagnosis and treatment of an extraoral cutaneous sinus tract originating in a mandibular second molar with a C-shaped root canal system. The patient was referred to our department by a dermatologist after a series of unsuccessful treatments, including antibiotics. Diffuse radiolucency on a preoperative radiograph revealed that earlier root canal treatment had been only partially successful. Consequently, we performed retreatment of the root canal comprising removal of the former restoration and gutta-percha, cleaning and shaping, and passive irrigation with sodium hypochlorite. The patient responded well, and the cutaneous lesion completely resolved uneventfully within 1 month postoperatively. Preoperative recognition and thorough knowledge of the root canal anatomy and conventional methods of obturation are necessary in performing successful endodontic treatment. PMID- 27665697 TI - Participation of Patient Community Members in Communication Classes for Dental Students at Tokyo Dental College. AB - In 2009, the Ministry of Education, Culture, Sports, Science and Technology launched its "Program for Promoting University Education and Student Support, Theme A: Program for Promoting University Education Reform". The ministry's stated aims were to 1) enhance student training centered on the needs of the individual patient; 2) improve their ability to make comprehensive diagnosis and treatment plans; and 3) instill high ethical standards and good communication skills. One of the main pillars of this project was to establish an educational organization aimed at encouraging public participation, the "Patient Community". The aim was to have members of this community roleplay patients in the Communication Studies component of the 1st-4th years of dental school. It was hoped that they would be able to respond to the students in a more realistic manner than simulated patients. Here, the number of Patient Community members and number who attended Communication Studies classes in 2010, 2011, 2012, and 2014 were investigated. The results showed that the number registered in the Patient Community increased annually, as did the number participating in Communication Studies classes, which rose in accordance with the number of classes held. No difference was observed in the number of attendees per Communication Studies class by grade (years 1-4). The number of members never attending Community Studies classes increased annually, although some members repeatedly attended. These findings suggest that the members who regularly participate tend to remain the same. PMID- 27665698 TI - Facile transformation of FeO/Fe3O4 core-shell nanocubes to Fe3O4 via magnetic stimulation. AB - Here, we propose the use of magnetic hyperthermia as a means to trigger the oxidation of Fe1-xO/Fe3-deltaO4 core-shell nanocubes to Fe3-deltaO4 phase. As a first relevant consequence, the specific absorption rate (SAR) of the initial core-shell nanocubes doubles after exposure to 25 cycles of alternating magnetic field stimulation. The improved SAR value was attributed to a gradual transformation of the Fe1-xO core to Fe3-deltaO4, as evidenced by structural analysis including high resolution electron microscopy and Rietveld analysis of X ray diffraction patterns. The magnetically oxidized nanocubes, having large and coherent Fe3-deltaO4 domains, reveal high saturation magnetization and behave superparamagnetically at room temperature. In comparison, the treatment of the same starting core-shell nanocubes by commonly used thermal annealing process renders a transformation to gamma-Fe2O3. In contrast to other thermal annealing processes, the method here presented has the advantage of promoting the oxidation at a macroscopic temperature below 37 degrees C. Using this soft oxidation process, we demonstrate that biotin-functionalized core-shell nanocubes can undergo a mild self-oxidation transformation without losing their functional molecular binding activity. PMID- 27665699 TI - Prediction of regioselectivity and preferred order of metabolisms on CYP1A2 mediated reactions. Part 1. Focusing on polycyclic arenes and the related chemicals. AB - This prediction system is based on placements of CYP1A2-substrates on a hexagonal grid template in a way following the rule generated from the relationship of the substrate-structure and selective-area uses on the template, and also the rule for a triggering-event to initiate the catalytic reactions. Clear relationship found between the placements and preferred-order of regioselective reactions from the comparison of experimental data of polyaromatic hydrocarbon (PAH)-substrates was implemented in this system. The template generated is consisted of two flat shape regions (Thin- and Thick-Areas) and Site of Oxidation. The latter is located at an overlapping region of Thin- and Thick-Areas and has a shape of cubic-like block. Thin-Area and Thick-Area are not on the same plane, and bend slightly at their overlapping parts. Two Entrances and two Gatekeepers are situated each near the top and middle bottleneck-parts of Thin-Area and Thick Area to restrict the substrate entry. A procedure of stepwise movement of substrates resided on Thick-Area is introduced to define the regioselectivity. A specific part (termed Trigger-Region) showing high placement rates was found at a region away from Site of Oxidation on the template, assuming that substrate sittings at Trigger-Region are essential for the initiation of catalytic reactions. These observations lead us an idea of simultaneous bi-molecule placement to fulfill both the essential sitting at Trigger-Region and regioselectivity of metabolisms, although a uni-molecule sitting co-covering Trigger-Region is also possible to contribute for the metabolite formation. Substrates of CYP1A2 are verified from distinct points including selective use of Thin-Area, Trigger-molecule Harboring Area, dual access routs, Facial-side Movement as well as their sizes. In addition, inhibitory actions as well region/stereo selective oxid/reductions of both PAH and non-PAH molecules are verified with their supposable interaction mechanisms in this prediction system. PMID- 27665701 TI - Does gender affect the outcome of community-acquired Staphylococcus aureus bacteraemia? PMID- 27665700 TI - Gene-gene interactions between DRD3, MRP4 and CYP2B6 polymorphisms and its influence on the pharmacokinetic parameters of efavirenz in HIV infected patients. AB - Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK parameters and genetic factors, which explain 50% of the variability in EFV PK parameters. The most relevant associations for metabolizing enzymes were found in CYP2B6 (rs3745274), in agreement with previous studies. The influence of transporters on the kinetics of EFV was also proved with significant correlations between the PK parameters of EFV and MRP4 (rs1751034, rs2274407). Analysis of gene-gene interactions with CYP2B6 was particularly useful to reinforce the role of MRP4 and to reveal unknown associations, such as that of DRD3. However, the role of DRD3 cannot be a direct effect but an indirect one due to physical proximity of NAT and the DRD3 locus in the genome. PMID- 27665702 TI - Promoting unbiased science on IgM-enriched immunoglobulins. PMID- 27665703 TI - Multidrug-resistant tuberculosis and migration to Europe. AB - Multidrug-resistant tuberculosis (MDR-TB) in low-incidence countries in Europe is more prevalent among migrants than the native population. The impact of the recent increase in migration to EU and EEA countries with a low incidence of TB (<20 cases per 100 000) on MDR-TB epidemiology is unclear. This narrative review synthesizes evidence on MDR-TB and migration identified through an expert panel and database search. A significant proportion of MDR-TB cases in migrants result from reactivation of latent infection. Refugees and asylum seekers may have a heightened risk of MDR-TB infection and worse outcomes. Although concerns have been raised around 'health tourists' migrating for MDR-TB treatment, numbers are probably small and data are lacking. Migrants experience significant barriers to testing and treatment for MDR-TB, exacerbated by increasingly restrictive health systems. Screening for latent MDR-TB is highly problematic because current tests cannot distinguish drug-resistant latent infection, and evidence-based guidance for treatment of latent infection in contacts of MDR patients is lacking. Although there is evidence that transmission of TB from migrants to the general population is low-it predominantly occurs within migrant communities-there is a human rights obligation to improve the diagnosis, treatment and prevention of MDR TB in migrants. Further research is needed into MDR-TB and migration, the impact of screening on detection or prevention, and the potential consequences of failing to treat and prevent MDR-TB among migrants in Europe. An evidence-base is urgently needed to inform guidelines for effective approaches for MDR-TB management in migrant populations in Europe. PMID- 27665704 TI - Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review. AB - OBJECTIVES: We conducted a systematic review to determine the diagnostic accuracy of whole genome sequencing (WGS) of Mycobacterium tuberculosis for the detection of resistance to first- and second-line anti-tuberculosis (TB) drugs. METHODS: The study was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews group. A total of 20 publications were included. The sensitivity, specificity, positive-predictive value and negative-predictive value of WGS using phenotypic drug susceptibility testing methods as a reference standard were determined. RESULTS: Anti-TB agents tested included all first-line drugs, a variety of reserve drugs, as well as new drugs. Polymorphisms in a total of 53 genes were tested for associations with drug resistance. Pooled sensitivity and specificity values for detection of resistance to selected first-line drugs were 0.98 (95% CI 0.93-0.98) and 0.98 (95% CI 0.98-1.00) for rifampicin and 0.97 (95% CI 0.94-0.99) and 0.93 (95% CI 0.91-0.96) for isoniazid, respectively. Due to high heterogeneity in study designs, lack of data, knowledge of resistance mechanisms and clarity on exclusion of phylogenetic markers, there was a significant variation in analytical performance of WGS for the remaining first line, reserved drugs and new drugs. CONCLUSIONS: Whole genome sequencing could be considered a promising alternative to existing phenotypic and molecular drug susceptibility testing methods for rifampicin and isoniazid pending standardization of analytical pipelines. To ensure clinical relevance of WGS for detection of M. tuberculosis complex drug resistance, future studies should include information on clinical outcomes. PMID- 27665705 TI - Comparison of the diagnostic power of cytokine patterns and procalcitonin for predicting infection among paediatric haematology/oncology patients. AB - OBJECTIVES: To evaluate the diagnostic power of the cytokine patterns and serum procalcitonin (PCT) level for predicting infection in paediatric haematology oncology patients. METHODS: Retrospective study including hospitalized children with haematology-oncology disease was conducted and their serum T helper type 1/type 2 cytokines were measured by a flow cytometric method. According to clinical symptoms, imaging and microbiological findings, febrile episodes were divided into five diagnostic groups serving as reference standard; and also grouped according to disease severity. A control group consisted of afebrile children. RESULTS: A total of 3023 samples (2819 febrile episodes and 204 control samples) derived from 992 children (including 164 afebrile control patients) were obtained. Interleukin-6 (IL-6) and IL-10 levels as well as their positivity rates were significantly higher among children with bacteraemia than for the viral infection and control groups. Among children with bacteraemia, 92.8% (297/320) and 82.2% (263/320) had increased IL-6 and IL-10 levels that exceeded the upper limit of the normal range, respectively. The positivity rates of PCT and C reactive protein were only 33.8% (108/320) and 73.1% (234/320), respectively, significantly lower than those of IL-6 and IL-10 (p <0.01). Based on the receiver operating characteristic curves, PCT exhibited poorer sensitivity in the diagnosis of severe infection compared with IL-6 and IL-10 (p <0.01). Specificity of IL-6 and IL-10 was significantly higher than that of PCT in the diagnosis of Gram-negative bacteraemia. CONCLUSION: Cytokine patterns of IL-6 and IL-10 showed higher diagnostic accuracy than PCT for bacteraemia and severe infections among febrile children with haematology/oncology disease. PMID- 27665706 TI - Cryptosporidium infections in Sweden-understanding the regional differences in reported incidence. PMID- 27665707 TI - Evaluating the performance of infectious disease forecasts: A comparison of climate-driven and seasonal dengue forecasts for Mexico. AB - Dengue viruses, which infect millions of people per year worldwide, cause large epidemics that strain healthcare systems. Despite diverse efforts to develop forecasting tools including autoregressive time series, climate-driven statistical, and mechanistic biological models, little work has been done to understand the contribution of different components to improved prediction. We developed a framework to assess and compare dengue forecasts produced from different types of models and evaluated the performance of seasonal autoregressive models with and without climate variables for forecasting dengue incidence in Mexico. Climate data did not significantly improve the predictive power of seasonal autoregressive models. Short-term and seasonal autocorrelation were key to improving short-term and long-term forecasts, respectively. Seasonal autoregressive models captured a substantial amount of dengue variability, but better models are needed to improve dengue forecasting. This framework contributes to the sparse literature of infectious disease prediction model evaluation, using state-of-the-art validation techniques such as out-of-sample testing and comparison to an appropriate reference model. PMID- 27665708 TI - Orthostatic changes in systolic blood pressure among SPRINT participants at baseline. AB - Orthostatic changes in systolic blood pressure (SBP) impact cardiovascular outcomes. In this study, we aimed to determine the pattern of orthostatic systolic pressure changes in participants enrolled in the SBP Intervention Trial (SPRINT) at their baseline visit before randomization and sought to understand clinical factors predictive of these changes. Of the 9323 participants enrolled in SPRINT, 8662 had complete data for these analyses. The SBP after 1 minute of standing was subtracted from the mean value of the three preceding seated SBP values. At the baseline visit, medical history, medications, anthropometric measures, and standard laboratory testing were undertaken. The mean age of SPRINT participants was 68 years, two-thirds were male, with 30% black, 11% Hispanic, and 55% Caucasian. The spectrum of SBP changes on standing demonstrated that increases in SBP were as common as declines, and about 5% of participants had an increase, and 5% had a decrease of >20 mm Hg in SBP upon standing. Female sex, taller height, more advanced kidney disease, current smoking, and several drug classes were associated with larger declines in BP upon standing, while black race, higher blood levels of glucose and sodium, and heavier weight were associated with more positive values of the change in BP upon standing. Our cross sectional results show a significant spectrum of orthostatic SBP changes, reflecting known (eg, age) and less well-known (eg, kidney function) relationships that may be important considerations in determining the optimal target blood pressure in long-term outcomes of older hypertensive patients. PMID- 27665709 TI - Circadian regulation of auditory function. AB - The circadian system integrates environmental cues to regulate physiological functions in a temporal fashion. The suprachiasmatic nucleus, located in the hypothalamus, is the master clock that synchronizes central and peripheral organ clocks to orchestrate physiological functions. Recently, molecular clock machinery has been identified in the cochlea unravelling the potential involvement in the circadian regulation of auditory functions. Here, we present background information on the circadian system and review the recent findings that introduce circadian rhythms to the auditory field. Understanding the mechanisms by which circadian rhythms regulate auditory function will provide fundamental knowledge on the signalling networks that control vulnerability and resilience to auditory insults. PMID- 27665711 TI - The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation. AB - The liver is essential for the synthesis of plasma proteins and integration of lipid metabolism. While the role of transcriptional networks in these processes is increasingly understood, less is known about post-transcriptional control of gene expression by RNA-binding proteins (RBPs). Here, we show that the RBP vigilin is upregulated in livers of obese mice and in patients with fatty liver disease. By using in vivo, biochemical and genomic approaches, we demonstrate that vigilin controls very-low-density lipoprotein (VLDL) secretion through the modulation of apolipoproteinB/Apob mRNA translation. Crosslinking studies reveal that vigilin binds to CU-rich regions in the mRNA coding sequence of Apob and other proatherogenic secreted proteins, including apolipoproteinC-III/Apoc3 and fibronectin/Fn1. Consequently, hepatic vigilin knockdown decreases VLDL/low density lipoprotein (LDL) levels and formation of atherosclerotic plaques in Ldlr /- mice. These studies uncover a role for vigilin as a key regulator of hepatic Apob translation and demonstrate the therapeutic potential of inhibiting vigilin for cardiovascular diseases. PMID- 27665710 TI - Involvement of Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury. AB - Advanced glycation end-products (AGEs)-induced mesangial cell death is one of major causes of glomerulus dysfunction in diabetic nephropathy. Both endoplasmic reticulum (ER) stress and autophagy are adaptive responses in cells under environmental stress and participate in the renal diseases. The role of ER stress and autophagy in AGEs-induced mesangial cell death is still unclear. Here, we investigated the effect and mechanism of AGEs on glomerular mesangial cells. AGEs dose-dependently decreased mesangial cell viability and induced cell apoptosis. AGEs also induced ER stress signals in a time- and dose-dependent manner. Inhibition of ER stress with 4-phenylbutyric acid effectively inhibited the activation of eIF2alpha and CHOP signals and reversed AGEs-induced cell apoptosis. AGEs also activated LC-3 cleavage, increased Atg5 expression, and decreased p62 expression, which indicated the autophagy induction in mesangial cells. Inhibition of autophagy by Atg5 siRNAs transfection aggravated AGEs induced mesangial cell apoptosis. Moreover, ER stress inhibition by 4 phenylbutyric acid significantly reversed AGEs-induced autophagy, but autophagy inhibition did not influence the AGEs-induced ER stress-related signals activation. These results suggest that AGEs induce mesangial cell apoptosis via an ER stress-triggered signaling pathway. Atg5-dependent autophagy plays a protective role. These findings may offer a new strategy against AGEs toxicity in the kidney. PMID- 27665712 TI - Bcl-xL dependency coincides with the onset of neurogenesis in the developing mammalian spinal cord. AB - The bcl-2 family of survival and death promoting proteins play a key role in regulating cell numbers during nervous system development. Bcl-xL, an anti apoptotic bcl-2 family member is highly expressed in the developing nervous system. However; the early embryonic lethality of the bcl-x germline null mouse precluded an investigation into its role in nervous system development. To identify the role of bcl-x in spinal cord neurogenesis, we generated a central nervous system-specific bcl-x conditional knockout (BKO) mouse. Apoptotic cell death in the BKO embryo was initially detected at embryonic day 11 (E11) in the ventrolateral aspect of the spinal cord corresponding to the location of motor neurons. Apoptosis reached its peak at E13 having spread across the ventral and into the dorsal spinal cord. By E18, the wave of apoptosis had passed and only a few apoptotic cells were observed. The duration and direction of spread of apoptosis across the spinal cord is consistent with the spatial and temporal sequence of neuronal differentiation. Motor neurons, the first neurons to become post mitotic in the spinal cord, were also the first apoptotic cells. As neurogenesis spread across the spinal cord, later born neuronal populations such as Lim2+ interneurons were also affected. The onset of apoptosis occurred in cells that had exited the cell cycle within the previous 24h and initiated neural differentiation as demonstrated by BrdU birthdating and betaIII tubulin immunohistochemistry. This data demonstrates that spinal cord neurons become Bcl xL dependent at an early post mitotic stage in developmental neurogenesis. PMID- 27665713 TI - Transcriptional control of physiological and pathological processes by the nuclear receptor PPARbeta/delta. PMID- 27665714 TI - Protective effects of the antioxidant extract collected from Styela clava tunics on UV radiation-induced skin aging in hairless mice. AB - Ultraviolet (UV) radiation is considered a primary cause of skin damage, which is characterized by deep wrinkles, roughness, laxity and pigmentation through oxidative stress and oxidative photodamage. To examine the therapeutic effects of ethanol extract of Styela clava tunics (EtSCT) on UV radiation-induced skin aging in hairless mice, alterations in skin phenotype, histological structures, inflammation, endoplasmic reticulum (ER) stress, oxidative conditions and toxicity were investigated during 13 weeks of UV irradiation and topical application of EtSCT. EtSCT showed high reducing power (3.1%), 2,2-diphenyl-1 picrylhydrazyl (DPPH) radical scavenging activity (92.7%) and NO scavenging activity (15.6%) due to its high total flavonoids (15.3 mg/ml) and total phenolics (36.8 mg/ml). The topical application of EtSCT suppressed photoaging of the skin of UV-irradiated mice, and this was demonstrated by the inhibition of wrinkle formation, the suppression of the erythema index as well as the prevention of transepidermal water loss. Additionally, the epidermal thickness and adipocytes number were recovered to a similar level as that in the no radiation group in the UV + EtSCT-treated groups compared with the UV + vehicle treated group, and the expression of collagen I increased. The attenuation of mitogen-activated protein kinase and ER stress signaling pathways activated by reactive oxygen species was also detected in the UV + EtSCT-treated group. Inflammatory responses including the infiltration of mast cells, CD31 expression and interleukin-6 secretion were significantly lower in the UV + EtSCT-treated groups. Moreover, the concentration of malondialdehyde was reduced and the activity of superoxide dismutase was effectively recovered in the UV + EtSCT treated groups compared with that in the vehicle-treated groups. Liver and kidney toxicity factors were maintained at a constant level. These results suggest that EtSCT has the potential for use as therapeutic drug which protects against skin aging by regulating the skin morphology, histopathological structures, ER stress, inflammation and oxidative conditions. PMID- 27665715 TI - Arsenic trioxide and triptolide synergistically induce apoptosis in the SKM-1 human myelodysplastic syndrome cell line. AB - Although certain combination therapies comprising arsenic trioxide (As2O3) with other agents exist for the treatment of several types of human cancer, few As2O3 combination therapies are clinically effective for myelodysplastic syndromes (MDS). Triptolide (TL) may be an effective therapeutic agent for the treatment of MDS. However, to date, there is no combination therapy for MDS with As2O3 and TL. Therefore, the aim of the present study was to investigate this combination therapy on the apoptosis of MDS SKM-1 cells. The MDS SKM-1 cells were treated with As2O3, TL or the two in combination at various concentrations, or were mock treated. Cell viability, cell apoptosis, levels of reactive oxygen species (ROS) and the expression of the cell apoptosis-associated genes, B cell lymphoma-2 (Bcl 2), Bcl-2-associated X protein (Bax) and caspase-3, were determined using an MTT assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide double-stained cells, flow cytometic analysis of intracellular 2',7' dichlorodihydrofluorescein diacetate fluorescence and reverse transcription quantitative polymerase chain reaction analysis, respectively. Combination index (CI) analysis was performed to determine whether effects were synergistic (CI<1). The combination treatment was found to synergistically inhibit MDS SKM-1 cell growth, induce cell apoptosis, increase ROS levels, upregulate the expression levels of Bax and caspase-3, and downregulate the mRNA expression of Bcl-2. In conclusion, the combination treatment of As2O3 and TL synergistically induced apoptosis in the MDS SKM-1 cells. PMID- 27665716 TI - Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard induced cell death by inhibiting the lipoxygenase pathway. AB - Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM-induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM-induced cell death. Among several antioxidants, CA partially alleviated SM-induced cell death in a dose-dependent manner. Although CA treatment decreased the phosphorylation of p38 mitogen-activated protein (MAP) kinase and p53, p38 MAP kinase inhibition by SB203580 did not affect SM-induced cell death. As CA has also been reported as a 15-lipoxygenase (15-LOX) inhibitor, the role of 15-LOX in SM-induced cytotoxicity was also examined. Similar to the results observed with CA, treatment with PD146176, a specific 15-LOX inhibitor, decreased SM-induced cytotoxicity, accompanied by decreases in the production of tumor necrosis factor-alpha and 15-hydroxyeicosatetraenoic acid. Furthermore, the present study investigated the protective effects of two natural 15-LOX inhibitors, morin hydrate and quercetin, in SM-induced cytotoxicity. As expected, these inhibitors had similar protective effects against SM-induced cytotoxicity. These antioxidants also reduced the generation of ROS and nitrate/nitrite. Therefore, the results of the present study indicated that the natural products, CA, quercetin and morin hydrate, offer potential as adjuvant therapeutic agents for SM-induced toxicity, not only by reducing inflammation mediated by the p38 and LOX signaling pathways, but also by decreasing the generation of ROS and nitrate/nitrite. PMID- 27665718 TI - Bacterial secretion: Reusing injected proteins. PMID- 27665720 TI - Virus Infection: HIV-1 weighs up risks and benefits. PMID- 27665721 TI - Archaeal biology: Archaeal virus escapology. PMID- 27665722 TI - Optimizing HIV pre-exposure prophylaxis implementation among men who have sex with men in a large urban centre: a dynamic modelling study. AB - INTRODUCTION: Once-daily tenofovir/emtricitabine-based pre-exposure prophylaxis (PrEP) can reduce HIV acquisition in men who have sex with men (MSM), by 44% in the iPrEx trial, and reaching up to 99% with high adherence. We examined the potential population-level impact and cost-effectiveness of different PrEP implementation strategies. METHODS: We developed a dynamic, stochastic compartmental model of HIV transmission among the estimated 57,400 MSM in Toronto, Canada. Parameterization was performed using local epidemiologic data. Strategies examined included (1) uniform PrEP delivery versus targeting the highest risk decile of MSM (with varying coverage proportions); (2) increasing PrEP efficacy as a surrogate of adherence (44% to 99%); and (3) varying HIV test frequency (once monthly to once yearly). Outcomes included HIV infections averted and the incremental cost ($CAD) per incremental quality-adjusted-life-year (QALY) gained over 20 years. RESULTS: Use of PrEP among all HIV-uninfected MSM at 25, 50, 75 and 100% coverage prevented 1970, 3427, 4317, and 4581 infections, respectively, with cost/QALY increasing from $500,000 to $800,000 CAD. Targeted PrEP for the highest risk MSM at 25, 50, 75 and 100% coverage prevented 1166, 2154, 2816, and 3012 infections, respectively, with cost/QALY ranging from $35,000 to $70,000 CAD. Maximizing PrEP efficacy, in a scenario of 25% coverage of high-risk MSM with PrEP, prevented 1540 infections with a cost/QALY of $15,000 CAD. HIV testing alone (Q3 months) averted 898 of infections with a cost savings of $4,000 CAD per QALY. CONCLUSIONS: The optimal implementation strategy for PrEP over the next 20 years at this urban centre is to target high-risk MSM and to maximize efficacy by supporting PrEP adherence. A large health benefit of PrEP implementation could come from engaging undiagnosed HIV-infected individuals into care. PMID- 27665723 TI - Direct and Versatile Synthesis of Red-Shifted Azobenzenes. AB - A straightforward synthesis of azobenzenes with bathochromically-shifted absorption bands is presented. It employs an ortho-lithiation of aromatic substrates, followed by a coupling reaction with aryldiazonium salts. The products are obtained with good to excellent yields after simple purification. Moreover, with the presented methodology, a structurally diverse panel of different azobenzenes, including unsymmetric tetra-ortho-substituted ones, can be readily obtained, which paves the way for future development of red-light addressable azobenzene derivatives for in vivo application. PMID- 27665717 TI - ESX secretion systems: mycobacterial evolution to counter host immunity. AB - Mycobacterium tuberculosis uses sophisticated secretion systems, named 6 kDa early secretory antigenic target (ESAT6) protein family secretion (ESX) systems (also known as type VII secretion systems), to export a set of effector proteins that helps the pathogen to resist or evade the host immune response. Since the discovery of the esx loci during the M. tuberculosis H37Rv genome project, structural biology, cell biology and evolutionary analyses have advanced our knowledge of the function of these systems. In this Review, we highlight the intriguing roles that these studies have revealed for ESX systems in bacterial survival and pathogenicity during infection with M. tuberculosis. Furthermore, we discuss the diversity of ESX systems that has been described among mycobacteria and selected non-mycobacterial species. Finally, we consider how our knowledge of ESX systems might be applied to the development of novel strategies for the treatment and prevention of disease. PMID- 27665719 TI - Harnessing the power of microbial autotrophy. AB - Autotrophic microorganisms convert CO2 into biomass by deriving energy from light or inorganic electron donors. These CO2-fixing microorganisms have a large, but so far only partially realized, potential for the sustainable production of chemicals and biofuels. Productivities have been improved in autotrophic hosts through the introduction of production pathways and the modification of autotrophic systems by genetic engineering. In addition, approaches are emerging in which CO2 fixation pathways and energy-harvesting systems are transplanted into heterotrophic model microorganisms. Alternative promising concepts are hybrid production systems of autotrophs and heterotrophs, and bio-inorganic hybrids of autotrophic microorganisms with electrocatalysts or light-harvesting semiconductor materials. In this Review, we discuss recent advances and bottlenecks for engineering microbial autotrophy and explore novel strategies that will pave the way towards improved microbial autotrophic production platforms. PMID- 27665724 TI - A naturally occurring bovine APOBEC3 confers resistance to bovine lentiviruses: implication for the co-evolution of bovids and their lentiviruses. AB - Mammals have co-evolved with lentiviruses for a long time. As evidence, viral infectivity factor (Vif), encoded by lentiviruses, antagonizes the anti-viral action of cellular APOBEC3 of their hosts. Here, we address the co-evolutionary dynamics of bovine APOBEC3 and the following two bovine lentiviruses: bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV). We determined the sequences of three APOBEC3 genes of bovids belonging to the genera Bos and Bison and showed that bovine APOBEC3Z3 is under a strong positive selection. We found that APOBEC3Z3 of gaur, a bovid in the genus Bos, acquired resistance to JDV Vif mediated degradation after diverging from the other bovids through conversion of the structural composition of the loop 1 domain. Interestingly, the resistance of gaur APOBEC3Z3 can be attributed to the positive selection of residue 62. This study provides the first evidence, suggesting that a co-evolutionary arms race between bovids and lentiviruses occurred in Asia. PMID- 27665725 TI - Kisspeptin mRNA expression is increased in the posterior hypothalamus in the rat model of polycystic ovary syndrome. AB - Hypersecretion of luteinizing hormone (LH) is a common endocrinological finding of polycystic ovary syndrome (PCOS). This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of gonadotropin-releasing hormone (GnRH). We evaluated the relationship between the hypothalamic-pituitary-gonadal axis (HPG axis) and kisspeptin using a rat model of PCOS induced by letrozole. Letrozole pellets (0.4 mg/day) and control pellets were placed subcutaneously onto the backs of 3-week-old female Wistar rats. Body weight, vaginal opening and vaginal smear were checked daily. Blood and tissues of ovary, uterus and brain were collected at 12-weeks of age. An hypothalamic block was cut into anterior and posterior blocks, which included the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), respectively, in order to estimate hypothalamic kisspeptin expression in each area. The letrozole group showed a similar phenotype to human PCOS such as heavier body weight, heavier ovary, persistent anovulatory state, multiple enlarged follicles with no corpus luteum and higher LH and testosterone (T) levels compared to the control group. Kisspeptin mRNA expression in the posterior hypothalamic block including ARC was higher in the letrozole group than in the control group although its expression in the anterior hypothalamic block was similar between groups. These results suggest that enhanced KNDy neuron activity in ARC contributes to hypersecretion of LH in PCOS and might be a therapeutic target to rescue ovulatory disorder of PCOS in the future. PMID- 27665726 TI - Manipulating carbohydrate metabolism to enhance regeneration (retrospective on DOI 10.1002/bies.201300110). PMID- 27665727 TI - Insights from a Small Wobble. PMID- 27665728 TI - Structural and histone binding ability characterization of the ARB2 domain of a histone deacetylase Hda1 from Saccharomyces cerevisiae. AB - Hda1 is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Though the N-terminal catalytic HDAC domain of Hda1 is well characterized, the function of the C-terminal ARB2 domain remains unknown. In this study, we determine the crystal structure of the ARB2 domain from S. cerevisiae Hda1 at a resolution of 2.7 A. The ARB2 domain displays an alpha/beta sandwich architecture with an arm protruding outside. Two ARB2 domain molecules form a compact homo-dimer via the arm elements, and assemble as an inverse "V" shape. The pull-down and ITC results reveal that the ARB2 domain possesses the histone binding ability, recognizing both the H2A-H2B dimer and H3-H4 tetramer. Perturbation of the dimer interface abolishes the histone binding ability of the ARB2 domain, indicating that the unique dimer architecture of the ARB2 domain coincides with the function for anchoring to histone. Collectively, our data report the first structure of the ARB2 domain and disclose its histone binding ability, which is of benefit for understanding the deacetylation reaction catalyzed by the class II Hda1 HDAC complex. PMID- 27665729 TI - New SMARCA2 mutation in a patient with Nicolaides-Baraitser syndrome and myoclonic astatic epilepsy. AB - We report a de novo SMARCA2 missense mutation discovered on exome sequencing in a patient with myoclonic astatic epilepsy, leading to reassessment and identification of Nicolaides-Baraitser syndrome. This de novo SMARCA2 missense mutation c.3721C>G, p.Gln1241Glu is the only reported mutation on exon 26 outside the ATPase domain of SMARCA2 to be associated with Nicolaides-Baraitser syndrome and adds to chromatin remodeling as a pathway for epileptogenesis. (c) 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID- 27665730 TI - Diagnostic value of positive urinary cytology in the detection of recurrent urothelial carcinoma: 10-Year Experience at the Papanicolaou Cytology Laboratory. AB - INTRODUCTION: Urothelial carcinoma (UCC) of the bladder is the most common malignancy of the urinary tract. The performance of urine cytology (UCy) after radical cystectomy (RC) and urinary diversion is quite variable and there is no consensus regarding its role in post-treatment surveillance. The goal of this study is to retrospectively review the diagnostic value of positive (suspicious or positive for malignancy) diverted urine cytology (DUCy) in the detection of urinary tract recurrence of UCC. MATERIALS AND METHODS: A retrospective 10-year (January 2005 to January 2015) computerized search for all DUCy specimens was conducted. All suspicious (Susp) or positive for malignant cells (PMC) ThinPrep cases were identified and retrospectively reviewed. Clinical, surgical, and pathological follow-up for patients with Susp or PMC UCy were tabulated and analyzed. RESULTS: During the 10-year-period, 1,525 DUCy cases from 408 patients were identified. Of these, 25 cases (1.64%) from 10 patients were called either Susp (13; 0.85%) or PMC (12; 0.79%). The 25 DUCy cases occurred within a mean of 20 months post-RC. Out of 10 patients, 9 had a concurrent biopsy or a subsequent resection of the recurrent site. Of these 9 patients, 8 (89%) had subsequent biopsy or resection, which showed recurrent UCC. In 5/8 patients, positive DUCy was the very first manifestation of recurrence, which was subsequently confirmed by imaging or histology. CONCLUSION: It is our experience that patients with positive UCy after RC have a high likelihood of recurrent UCC and should be counseled and managed accordingly. Diagn. Cytopathol. 2016;44:975-979. (c) 2016 Wiley Periodicals, Inc. PMID- 27665731 TI - Multiple unilaterally localized dermatofibromas in a patient with Down syndrome. PMID- 27665732 TI - Chinese children's imaginary companions: Relations with peer relationships and social competence. AB - We investigated relationships between Chinese children's imaginary companions (ICs) and peer relationships and social competence in 160 children, aged 5-6 years old. Children and their mothers participated in the interviews regarding the details of the children's ICs, including the type of the companion and the quality of the child-IC relationship. Peer relationships were assessed using sociometric nomination and perceived popularity nomination. Teachers rated children's social competence. Here, 55 children (34.3%) were deemed to have engaged in imaginary companion play. There was no relationship between imaginary companion types and child-IC relationship qualities. Children with invisible friends received more positive nominations than children with personified objects. Children with egalitarian relationships received more positive nominations and popularity nominations, but fewer negative nominations and unpopularity nominations than children with hierarchical relationships. Compared with children with hierarchical relationships, teachers rated the children with egalitarian relationships higher in social competence. The results suggest that imaginary companion types and relationship qualities may represent different dimensions of imaginary companions, calling attentions to the different mechanisms underlying imaginary companion types and relationship qualities with respect to social functioning. PMID- 27665733 TI - Programmed death-1+ T cells inhibit effector T cells at the pathological site of miliary tuberculosis. AB - Optimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is a key immune check-point receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to Mycobacterium tuberculosis infection, leading to disseminated disease such as miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathological site, remains to be addressed. The objective of this study was to investigate the role of PD-1-PD-ligand 1 (PD-L1) in T cell responses at the pathological site from patients of TB pleurisy and MTB as clinical models of contained and disseminated forms of tuberculosis, respectively. We examined the expression and function of PD-1 and its ligands (PD L1-PD-L2) on host immune cells among tuberculosis patients. Bronchoalveolar lavage-derived CD3 T cells in MTB expressed PD-1 (54.2 +/- 27.4%, P >= 0.0009) with significantly higher PD-1 ligand-positive T cells (PD-L1: 19.8 +/- 11.8%; P >= 0.019, PD-L2: 12.6 +/- 6.2%; P >= 0.023), CD19+ B cells (PD-L1: 14.4 +/- 10.4%; P >= 0.042, PD-L2: 2.6 +/- 1.43%; not significant) and CD14+ monocytes (PD L1: 40.2 +/- 20.1%; P >= 0.047, PD-L2: 22.4 +/- 15.6%; P >= 0.032) compared with peripheral blood (PB) of MTB and healthy controls. The expression of PD-1 was associated with a diminished number of cells producing effector cytokines interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-2 and elevated apoptosis. Locally accumulated T cells were predominantly PD-1+ -PD L1+ , and blocking this pathway restores the protective T cell response. We conclude that M. tuberculosis exploits the PD-1 pathway to evade the host immune response by altering the T helper type 1 (Th1) and Th2 balance at the pathological site of MTB, thereby favouring disease dissemination. PMID- 27665734 TI - Matrine induces cell cycle arrest and apoptosis with recovery of the expression of miR-126 in the A549 non-small cell lung cancer cell line. AB - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality in the United States. Chemotherapy prolongs survival rates among patients with advanced disease, however, this is at the cost of clinically significant adverse effects. Matrine is an active component of traditional Chinese medicine and is a promising alternative drug for the treatment of NSCLC. In the present study, the therapeutic effects and the underlying molecular mechanisms of matrine on the A549 NSCLC cell line were investigated. A high concentration of matrine (1.0 mg/ml) significantly (P<0.05) inhibited cell proliferation, by 52.68+/-3.32%, under which cell shrinkage and disruption were observed. Flow cytometric analysis showed that the proportion of G1/G0 cells was significantly increased, whereas the proportions of S and G2/M cells were significantly decreased (P<0.05) following treatment with matrine for 48 h. These results indicated that cell arrest was induced by matrine. Upregulation of the expression of microRNA (miR)-126, followed by downregulation of the expression of its target gene, vascular endothelial growth factor, were detected following treatment with a low concentration of matrine (0.2 mg/ml) using reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. In conclusion, matrine induced cell cycle arrest and apoptosis, and recovered the expression of miR-126 in the A549 NSCLC cell line. PMID- 27665736 TI - Involvement of DR4/JNK pathway-mediated autophagy in acquired TRAIL resistance in HepG2 cells. AB - Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, a number of cancer cells demonstrate TRAIL resistance. To date, various molecular targets leading to TRAIL resistance have been elucidated by many researchers, but the mechanisms involved are still not fully understood. In the present study, we obtained TRAIL-resistant cells from the human hepatocellular carcinoma cell line HepG2 by exposing cells to recombinant human TRAIL (rhTRAIL), and determined a mechanism for TRAIL resistance. The selected TRAIL-resistant cells (HepG2-TR) were insensitive to rhTRAIL and triggered autophagy in response to rhTRAIL. The inhibition of autophagy by 3-methyladenine or the knockdown of ATG5 partially restored rhTRAIL induced apoptosis and cytotoxicity, indicating that protective autophagy occurred in the cells. Notably, rhTRAIL-induced autophagy was mediated through DR4 in HepG2-TR cells, but not in parental HepG2 cells. In addition, the c-Jun N terminal kinase was involved in DR4-mediated autophagy in HepG2-TR cells. Our results suggest a novel mechanism of TRAIL resistance which is regulated through alterations in DR4 function, which may extend our understanding of the mechanisms of TRAIL resistance. PMID- 27665735 TI - The molecular and phenotypic spectrum of IQSEC2-related epilepsy. AB - OBJECTIVE: IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. METHODS: Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. RESULTS: Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. SIGNIFICANCE: The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy. PMID- 27665737 TI - Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process. AB - Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI. PMID- 27665738 TI - Validating a proxy for disease progression in metastatic cancer patients using prescribing and dispensing data. AB - BACKGROUND: Routine data collections are used increasingly to examine outcomes of real-world cancer drug use. These datasets lack clinical details about important endpoints such as disease progression. AIM: To validate a proxy for disease progression in metastatic cancer patients using prescribing and dispensing claims. METHODS: We used data from a cohort study of patients undergoing chemotherapy who provided informed consent to the collection of cancer-treatment data from medical records and linkage to pharmaceutical claims. We derived proxy decision rules based on changes to drug treatment in prescription histories (n = 36 patients) and validated the proxy in prescribing data (n = 62 patients). We adapted the decision rules and validated the proxy in dispensing data (n = 109). Our gold standard was disease progression ascertained in patient medical records. Individual progression episodes were the unit of analysis for sensitivity and Positive Predictive Value (PPV) calculations and specificity and Negative Predictive Value (NPV) were calculated at the patient level. RESULTS: The sensitivity of our proxy in prescribing data was 74.3% (95% Confidence Interval (CI), 55.6-86.6%) and PPV 61.2% (95% CI, 45.0-75.3%); specificity and NPV were 87.8% (95% CI, 73.8-95.9%) and 100% (95% CI, 90.3-100%), respectively. In dispensing data, the sensitivity of our proxy was 64% (95% CI, 55.0-77.0%) and PPV 56.0% (95% CI, 43.0-69.0%); specificity and NPV were 81% (95% CI, 70.05 89.0%) and 91.0% (95% CI, 82.0-97.0%), respectively. CONCLUSION: Our proxy overestimated episodes of disease progression. The proxy's performance is likely to improve if the date of prescribing is used instead of date of dispensing in claims data and by incorporating medical service claims (such as imaging prior to drug changes) in the algorithm. Our proxy is not sufficiently robust for use in real world comparative effectiveness research for cancer medicines. PMID- 27665739 TI - MicroRNA miR-374, a potential radiosensitizer for carbon ion beam radiotherapy. AB - In this study, we compared the microRNA (miRNA) profiles of a control and X-ray- and carbon ion beam-resistant cells to identify miRNAs that can be used as radiosensitizers and biomarkers. Mouse squamous cell carcinoma line NR-S1, its X ray-resistant derivative X60, and its carbon ion beam-resistant derivative C30 were subjected to miRNA microarray analysis. Expression of miRNAs shown to be upregulated or downregulated in the microarray analysis was confirmed by qRT-PCR. Downregulated miRNAs were overexpressed in human pancreatic cancer cell lines PANC1 and MIA PaCa-2, and the resulting cells were tested for radiosensitivity using colony-forming and sphere-forming assays. Of 1,265 miRNAs analyzed, 4 were downregulated and 11 were upregulated in X-ray-resistant and carbon ion beam resistant cells. Two of the downregulated miRNAs, miR-196 and miR-374, were selected for overexpression in PANC1 and MIA PaCa-2 cells. Overexpression of miR 374 sensitized PANC-1 and MIA PaCa-2 cells toward carbon ion beam radiation. miRNA miR-374 has the potential to be a new radiosensitizer for carbon ion beam radiotherapy and a new biomarker to determine the optimal treatment for cancer. PMID- 27665740 TI - A prospective, cohort evaluation of major and minor airway management complications during routine anaesthetic care at an academic medical centre. AB - The aim of this study was to develop an audit tool to identify prospectively all peri-operative adverse events during airway management in a cost-effective and reproducible way. All patients at VU University Medical Center who required general anaesthesia for elective and emergency surgical procedures were included during a period of 8 weeks. Daily questionnaires and interviews were taken from anaesthesia trainees and anaesthetic department staff members. A total of 2803 patients underwent general anaesthesia, 1384 men and 1419 women, including 2232 elective patients and 571 emergency procedures, 697 paediatric and 2106 adult surgical procedures. A total of 168 airway-related events were reported. The incidence of severe airway management-related events was 24/2803 (0.86%). There were 12 (0.42%) unanticipated ICU admissions, two patients (0.07%) required a surgical airway. There was one (0.04%) death, one cannot intubate cannot oxygenate (0.04%), one aspiration (0.04%) and eight (0.29%) severe desaturations < Sp O2 50%. We suggest that our method to determine and investigate airway management-related adverse events could be adopted by other hospitals. PMID- 27665741 TI - Paraspeckles modulate the intranuclear distribution of paraspeckle-associated Ctn RNA. AB - Paraspeckles are sub-nuclear domains that are nucleated by long noncoding RNA Neat1. While interaction of protein components of paraspeckles and Neat1 is understood, there is limited information on the interaction of non-structural RNA components with paraspeckles. Here, by varying paraspeckle number and size, we investigate how paraspeckles influence the nuclear organization of their non structural RNA component Ctn RNA. Our results show that Ctn RNA remains nuclear retained in the absence of intact paraspeckles, suggesting that they do not regulate nuclear retention of Ctn RNA. In the absence of Neat1, Ctn RNA continues to interact with paraspeckle protein NonO to form residual nuclear foci. In addition, in the absence of Neat1-nucleated paraspeckles, a subset of Ctn RNA localizes to the perinucleolar regions. Concomitant with increase in number of paraspeckles, transcriptional reactivation resulted in increased number of paraspeckle-localized Ctn RNA foci. Similar to Neat1, proteasome inhibition altered the localization of Ctn RNA, where it formed enlarged paraspeckle-like foci. Super-resolution structured illumination microscopic analyses revealed that in paraspeckles, Ctn RNA partially co-localized with Neat1, and displayed a more heterogeneous intra-paraspeckle localization. Collectively, these results show that while paraspeckles do not influence nuclear retention of Ctn RNA, they modulate its intranuclear compartmentalization. PMID- 27665742 TI - Evaluation of the safety in dogs of long-term, daily oral administration of capromorelin, a novel drug for stimulation of appetite. AB - The objective of the study was to evaluate the safety of capromorelin, a ghrelin agonist that stimulates appetite and causes increased body weight and the release of growth hormone (GH). Beagle dogs (n = 32) received either oral placebo or 0.3, 7, or 40 mg/kg capromorelin once daily for 12 consecutive months. Safety was evaluated by physical examinations, including ECG and ophthalmic examinations, and comprehensive clinical pathology. Serum levels of capromorelin, GH, and insulin-like growth factor 1 (IGF-1) were measured periodically. Necropsies and histopathological evaluations were performed at study termination. As expected, GH and IGF-1 levels were mildly increased in capromorelin-treated dogs. Adverse events were limited to mild emesis and loose stools in all groups and excess salivation among some dogs receiving higher capromorelin doses. Clinical pathology testing was generally normal, although blood lipids and alkaline phosphatase levels were moderately increased among dogs receiving capromorelin. Treated dogs had slightly longer post-treatment PR intervals seen on ECG, but with no changes in cardiac histopathology. Postmortem findings were normal. Drug related increases in liver weight were linked to overall increases in body weight. Capromorelin was well tolerated in dogs at daily doses up to 40 mg/kg for 12 months, demonstrating a wide safety margin. PMID- 27665743 TI - Compartmentalized gene expression profiling of receptive endometrium reveals progesterone regulated ENPP3 is differentially expressed and secreted in glycosylated form. AB - The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation. Interestingly, there was high expression of ENPP3 mRNA in stroma but not protein. Presence of N-glycosylated ENPP3 in receptive phase uterine fluid in women confirms its regulation by progesterone and makes it possible to use in a non-invasive test of endometrial receptivity. PMID- 27665745 TI - Exploring Cognitive Relations Between Prediction in Language and Music. AB - The online processing of both music and language involves making predictions about upcoming material, but the relationship between prediction in these two domains is not well understood. Electrophysiological methods for studying individual differences in prediction in language processing have opened the door to new questions. Specifically, we ask whether individuals with musical training predict upcoming linguistic material more strongly and/or more accurately than non-musicians. We propose two reasons why prediction in these two domains might be linked: (a) Musicians may have greater verbal short-term/working memory; (b) music may specifically reward predictions based on hierarchical structure. We provide suggestions as to how to expand upon recent work on individual differences in language processing to test these hypotheses. PMID- 27665744 TI - Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers. AB - Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a "double hit score" upon positivity for BCL2 and MYC. PCDLBCL-NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B-cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a "non-germinal B-cell" profile, whereas "germinal center" cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC-LT, which often coexpressed MYC and BCL2. The impact of single factors on 5-year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group-PCDLBCL-NOS-exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information. PMID- 27665747 TI - Upregulation and activation of delta-opioid receptors promotes the progression of human breast cancer. AB - delta-opioid receptor (DOR) belongs to the family of G protein-coupled receptors (GPCRs). Numerous studies have shown that DOR is widely distributed in human peripheral tissues and is closely related to the development and progression of certain malignant tumours. However, there is controversy in the literature regarding whether DOR has an impact on the development and progression of human breast cancer. The present study comprehensively elaborates on the biological functions of DOR by determining the distribution of DOR expression in breast cancer tissues and cells and by further verifying the effects of DOR on breast cancer progression. DOR was found to be highly expressed in human breast cancer tissues and cells. In addition, the high expression level of DOR positively correlated with tumour grade and clinical stage and negatively correlated with breast cancer metastasis and prognosis. Upregulating and activating DOR promoted the proliferation of human breast cancer cells in a concentration-dependent manner within a specific concentration range, whereas downregulating or inhibiting DOR activation significantly suppressed cell proliferation. The majority of tumour cells were arrested in G1 phase, and some cells exhibited apoptosis. DOR upregulation and activation induced protein kinase C (PKC) activation, resulting in increased phosphorylation levels of extracellular signal regulated kinases (ERKs). After inhibition of the PKC/ERK signalling pathway, the effects of DOR on breast cancer were significantly attenuated in vivo and in vitro. In summary, DOR is highly expressed in breast cancer and is closely related to its progression. These results suggest that DOR may serve as a potential biomarker for the early diagnosis of breast cancer and may be a viable molecular target for therapeutic intervention. PMID- 27665746 TI - The motility of esophageal sphincters during liquid and solid bolus swallows: a multicenter normative value study of high-resolution manometry in China. AB - BACKGROUND: It is gradually accepted that solid bolus swallow needs to be added to the procedure of manometry. The motility differences in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES) were not well described. Sierra Scientific Instruments solid-state high-resolution manometry (HRM) system, the most popular HRM system in China, lacks the Chinese normative values for both liquid and solid bolus swallow parameters. METHODS: The esophageal HRM data of 88 healthy volunteers were analyzed. The parameters of both sphincters in resting stage were summarized and those during solid and liquid swallows were compared. KEY RESULTS: Normative HRM values of sphincter parameters in solid and liquid bolus swallows in China were established. The UES residual pressure of solid bolus swallows was lower than that of liquid bolus (0.3+/-5.5 mm Hg vs 4.8+/-5.9 mm Hg, P=.000). The time parameters of UES relaxation between two types of bolus swallows were similar. In solid bolus swallows, the intrabolus pressure (IBP) (13.8+/-5.1 mm Hg vs 10.9+/-5.7 mm Hg, P=.000) and LES relaxation time (11.0+/ 2.1 seconds vs 8.7+/-1.3 seconds, P=.000) were higher. The 4-second integrated relaxation pressure between both bolus swallows was similar. CONCLUSIONS & INFERENCES: The function of the UES and LES between solid and liquid bolus swallows is different. Chinese HRM parameters are different from the Chicago Classification (http://www.chictr.org.cn, Number ChiCTR-EOC-15007147). PMID- 27665748 TI - Implant Stability Quotients of Osteotome Bone Expansion and Conventional Drilling Technique for 4.1 mm Diameter Implant at Posterior Mandible. AB - BACKGROUND: Clinical conclusions in studying the stability and osseointegration of mandibular implants positioned using the bone expansion techniques are conflicting and limited. PURPOSE: The objective was to examine the implant stability quotient (ISQ) values of mandibular posterior dental implants with 4.1 mm diameter that inserted with osteotome bone expansion technique versus conventional drilling technique during a 12-week observation period. MATERIALS AND METHODS: Twenty-four implants with 4.1mm diameter in 18 patients were included. Twelve implants in 10 patients were positioned using osteotome bone expansion technique, and 12 fixtures in 9 patients were installed using the conventional drilling technique. The ISQ values of a 3.3 mm diameter implant was measured at recipient sites (ISQb ) before final drilling or expansion technique to standardize the increased ISQ value of 4.1 mm diameter implants. The ISQ values at Weeks 0, 1, 2, 3, 4, 6, 8, 10, and 12 post-surgery were recorded. Data were analyzed by Wilcoxon rank sum test, repeated measure ANOVA, and Fisher Lest Significant Difference test. RESULTS: Calibrated according to a 3.3-mm-diameter implant, bone expansion technique was adopted for the sites with ISQ?65 bone density, and the areas with ISQ >65 bone condition were treated with conventional drilling technique (p =.038). Both groups presented a similar healing pattern and a comparable ISQ reading from Week 0 to Week 12 (p > .05) for 4.1 mm diameter implants. However, bone expansion technique could enhance more stability when the ISQ values were calibrated by 3.3 mm diameter implant (p < .05). CONCLUSIONS: Bone expansion technique substantially increased more ISQ values from primary stability and achieved comparable primary and secondary stabilities with the conventional technique. Both groups reached a stability plateaus at Week 10. PMID- 27665749 TI - Bioluminophore and Flavin Mononucleotide Fluorescence Quenching of Bacterial Bioluminescence-A Theoretical Study. AB - Bacterial bioluminescence with continuous glow has been applied to the fields of environmental toxin monitoring, drug screening, and in vivo imaging. Nonetheless, the chemical form of the bacterial bioluminophore is still a bone of contention. Flavin mononucleotide (FMN), one of the light-emitting products, and 4a-hydroxy-5 hydro flavin mononucleotide (HFOH), an intermediate of the chemical reactions, have both been assumed candidates for the light emitter because they have similar molecular structures and fluorescence wavelengths. The latter is preferred in experiments and was assigned in our previous density functional study. HFOH displays weak fluorescence in solutions, but exhibits strong bioluminescence in the bacterial luciferase. FMN shows the opposite behavior; its fluorescence is quenched when it is bound to the luciferase. This is the first example of flavin fluorescence quenching observed in bioluminescent systems and is merely an observation, both the quenching mechanism and quencher are still unclear. Based on theoretical analysis of high-level quantum mechanics (QM), combined QM and molecular mechanics (QM/MM), and molecular dynamics (MD), this paper confirms that HFOH in its first singlet excited state is the bioluminophore of bacterial bioluminescence. More importantly, the computational results indicate that Tyr110 in the luciferase quenches the FMN fluorescence via an electron-transfer mechanism. PMID- 27665750 TI - The seasonal importance of serum 25-hydroxyvitamin D for bone mineral density in older women. AB - BACKGROUND: The impact of season when determining a serum 25-hydroxyvitamin D (S 25OHD) cut-off level for optimal bone health is unknown. OBJECTIVE: To investigate the relative importance of S-25OHD for bone mineral density (BMD) by season. METHODS: A subcohort of 5002 Swedish women (mean age 68 years), randomly selected from a large population-based longitudinal cohort study with repeat dietary and lifestyle information, was enrolled during 2003-2009 for a clinical examination, which included dual-energy X-ray absorptiometry and collection of fasting blood samples. Categories of vitamin D status were determined by S-25OHD (measured by HPLC-MS/MS). RESULTS: In samples collected during summer, we found a gradual increase in BMD of the total hip up to a S-25OHD level of 40 nmol L-1 (6% of the cohort). In women with S-25OHD concentrations below 30 nmol L-1 during summer, adjusted BMD was 11% lower [95% confidence interval (CI) 3-19] and in those with S-25OHD levels of 30-40 nmol L-1 BMD was 6% lower (95% CI 1-11), compared with women with S-25OHD levels above 80 nmol L-1 . Low S-25OHD concentrations during summer (<30 nmol L-1 ) were also associated with higher adjusted relative risk of osteoporosis (4.9; 95% CI 2.9-8.4) compared with concentrations above 80 nmol L-1 . By contrast, no differences in mean BMD values between categories of S-25OHD were found during winter. CONCLUSIONS: Summer concentrations of S-25OHD appear to be the most useful to predict BMD, whereas winter levels have limited value. To determine a S-25OHD cut-off level for vitamin D deficiency, it may be necessary to take into account the season of blood collection. PMID- 27665751 TI - Identification of cyclic lipopeptides produced by Bacillus vallismortis R2 and their antifungal activity against Alternaria alternata. AB - AIM: To identify the different antifungal biomolecules produced by isolate Bacillus vallismortis R2 and analyse their effect on Alternaria alternata, a common pathogen causing black point disease of wheat. METHODS AND RESULTS: The different antifungal molecules produced by isolate R2 were purified by column chromatography. The liquid chromatography-mass spectrometry of purified fractions confirmed the ability of R2 to produce biomolecules putatively similar to three different families of cyclic lipopeptides (CLPs) viz. surfactins, iturins and fengycins. The synergistic interaction among CLPs was evident from significant increase in the antifungal activity of mixture of purified fractions as compared to that of the individual fractions by agar well diffusion assay. The evaluation of antifungal activity of purified fractions by 96-well microtitre plate assay showed that the fengycin-like molecules supported significantly higher antifungal activity against A. alternata than iturin A and no antifungal activity was supported by surfactin. CONCLUSIONS: The isolate R2, producing different CLPs, can be used as an environmental friendly alternative to chemical fungicides. Among the three different CLPs viz. surfactin, iturin A and fengycin produced by R2, the fengycins were the most active lipopeptides. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on co-production of three different types of CLPs by the cells of B. vallismortis. PMID- 27665752 TI - Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature. AB - One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. PMID- 27665753 TI - Modes of Decision Making Used by Nursing Home Residents and Their Families When Confronted With Potential Hospital Readmission. AB - The purpose of the current study was to characterize the decision-making processes used by nursing home (NH) residents and their families when confronted with an acute change in condition and the choice of transfer to the hospital or treatment in the NH. Using cognitive task analysis, 96 residents and 75 family members from 19 NHs were asked how they would make this choice. Fifty-one residents (53%) and 61 family members (81%) used a deliberative mode characterized by seeking information and weighing risks and benefits. Ten residents (10%) and five family members (7%) used a predominantly emotion-based mode characterized by references to feelings and prior experiences in these facilities. Thirty-six residents (38%) and nine family members (12%) delegated the decision to a family member or provider. Age and resident/family status were associated with mode used; transfer choice, gender, religion, education, and ethnic group were not. Although classic theories of information processing posit two modes of decision making, deliberative and affective, the current data suggest a third mode, that of delegating the decision to trusted others, particularly family members and providers. [Res Gerontol Nurs. 2016; 9(6):288 299.]. PMID- 27665754 TI - Effects of Support Groups for Individuals with Early-Stage Dementia and Mild Cognitive Impairment: An Integrative Review. AB - Support groups have demonstrated promising outcomes for individuals with mild cognitive impairment (MCI) and early-stage dementia (ESD) in previous literature reviews. However, evidence has not been updated since 2007. The current review aimed to update current evidence on the use and effects of support groups for individuals with MCI and ESD and their care partners. A literature search was conducted in seven databases and 18 eligible research articles were retrieved. Support groups showed positive impacts on participant acceptance of cognitive impairment; performance and satisfaction of meaningful activity; resilience; self help; and care partner coping self-efficacy, perceived support, and preparation and task effectiveness. Findings also revealed that support groups were well accepted by participants and care partners. Few studies included ethnic diversity, limiting the generalizability of findings. Further large-scale studies are needed to confirm the effects of support groups for individuals with MCI and ESD in all populations. [Res Gerontol Nurs. 2017; 10(1):35-51.]. PMID- 27665755 TI - Predicting Off-Label Antipsychotic Medication Use in a Randomly Selected Nursing Home Sample Based on Resident and Facility Characteristics. AB - Reducing off-label antipsychotic medication use for behavioral and psychological symptoms of dementia (BPSD) in nursing home residents has been a centerpiece of government regulation, but without insight into utilization differences based on resident and facility characteristics. To examine whether resident and facility characteristics can predict off-label antipsychotic medication treatment for BPSD, residents prescribed antipsychotic medication (N = 216) from 17 Maryland nursing facilities were randomly selected. Based on physician diagnoses, 59.7% of participants were taking off-label antipsychotic medications for BPSD. Hierarchical logistic regression results suggest that dementia level (indicated by Brief Cognitive Assessment Tool scores) and age, but not facility characteristics, significantly predict greater likelihood of using off-label antipsychotic medications for BPSD. Having moderate-severe dementia was associated with more than a four-fold increase in off-label antipsychotic medication use for BPSD. Off-label use of antipsychotic medications for BPSD remains high, especially for older nursing home residents with more severe dementia, indicating that more targeted reduction approaches are needed. [Res Gerontol Nurs. 2016; 9(6):257-266.]. PMID- 27665756 TI - Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review. AB - Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. PMID- 27665757 TI - Catalases and PhoB/PhoR system independently contribute to oxidative stress resistance in Vibrio cholerae O1. AB - All cells are subjected to oxidative stress, a condition under which reactive oxygen species (ROS) production exceeds elimination. Bacterial defences against ROS include synthesis of antioxidant enzymes like peroxidases and catalases. Vibrio cholerae can produce two distinct catalases, KatB and KatG, which contribute to ROS homeostasis. In this study, we analysed the mechanism behind katG and katB expression in two V. cholerae O1 pandemic strains, O395 and N16961, of classical and El Tor biotypes, respectively. Both strains express these genes, especially at stationary phase. However, El Tor N16961 produces higher KatB and KatG levels and is much more resistant to peroxide challenge than the classical strain, confirming a direct relationship between catalase activity and oxidative stress resistance. Moreover, we showed that katG and katB expression levels depend on inorganic phosphate (Pi) availability, in contrast to other bacterial species. In N16961, katB and katG expression is reduced under Pi limitation relative to Pi abundance. Total catalase activity in N16961 and its phoB mutant cells was similar, independently of growth conditions, indicating that the PhoB/PhoR system is not required for katB and katG expression. However, N16961 cells from Pi-limited cultures were 50-100-fold more resistant to H2O2 challenge and accumulated less ROS than phoB mutant cells. Together, these findings suggest that, besides KatB and KatG, the PhoB/PhoR system is an important protective factor against ROS in V. cholerae N16961. They also corroborate previous results from our and other groups, suggesting that the PhoB/PhoR system is fundamental for V. cholerae biology. PMID- 27665758 TI - Piscinibacterium candidicorallinum gen. nov., sp. nov., a member of the order Burkholderiales isolated from a fish pond. AB - A bacterial strain designated LYH-15T was isolated from a freshwater fish pond in Taiwan and characterized using a polyphasic taxonomy approach. Cells of LYH-15T were Gram-staining-negative, aerobic, motile by means of a single polar flagellum, poly-beta-hydroxybutyrate-containing, non-spore forming, straight rods and formed light-coral-colored colonies. Growth occurred at 15-40 degrees C (optimum, 30 degrees C), at pH 5.0-9.0 (optimum, pH 7.0) and with 0-0.5 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that LYH-15T forms a distinct phyletic line within the order Burkholderiales, with less than 94 % sequence similarity to its closest relatives with validly published names. The predominant fatty acids were summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0 and C18 : 1omega7c. The major isoprenoid quinone was Q-8 and the DNA G+C content was 63.8 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized lipids. The major polyamines were 2-hydroxyputrescine and putrescine. On the basis of the genotypic and phenotypic data, LYH-15T represents a novel species of a new genus in the order Burkholderiales, for which the name Piscinibacterium candidicorallinum gen. nov., sp. nov. is proposed. The type strain is LYH-15T (=BCRC 80969T=LMG 29480T=KCTC 52168T). PMID- 27665759 TI - Erratum to: Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors. PMID- 27665761 TI - The proliferation mechanism of normal and pathological human placentas. AB - The placenta, which is a regulator organ for many metabolic activities between mother and fetus, is critical in influencing the outcome of pregnancy. Therefore, fetal growth is directly related to the placental development. Placental development depends on the coordinated action of trophoblast proliferation, differentiation and invasion. Studies on cell cycle related proteins that control these events are limited. Abnormal placental development is linked to various pregnancy pathologies such as preeclampsia, intrauterine growth restriction, diabetes mellitus and gestational trophoblastic diseases. The cell cycle mechanism of human placenta should be well understood for a healthy pregnancy outcome. Moreover, how cell cycle related proteins that control placental development are affected in pregnancy pathologies is not fully understood yet. Therefore, the aim of this review is to address the currently available knowledge on cell cycle regulatory proteins involved in human placental development and on the expression differences of these proteins in pathological placentas. PMID- 27665760 TI - Previously undiagnosed diastematomyelia with bony spur as a cause of back pain in a 49-year-old patient with known psoriatic arthritis. PMID- 27665762 TI - [Assessment of Three Risk Adjustment Systems as Predictors of the Consumption of Medicines and Medical Supplies at Polyvalent Hospitalization Units. Spain]. AB - OBJECTIVE: The use of medicines and medical supplies is a significant component of health expenditure, linked to healthcare quality and efficient resource allocation. This study aimed to evaluate three risk adjustment systems predictive power of the consumption of medicines and medical supplies at polyvalent hospitalization units (PHU). METHODS: This is an observational, retrospective study of the resources utilization in PHU between 2010 and 2013. We fitted linear regression models and evaluated their goodness of fit for three different predictors: Charlson Comorbidity Index (CCI), All Patients DRG (AP-DRG) and All Patients Refined DRG (APR-DRG) relative weights, and each one of them corrected by the length of stay. We analyzed hospitalization episodes included in the Minimum Basic Data Set (MBDS) from Fuenlabrada University Hospital. Data about the use of medicines and medical supplies were obtained from pharmacy and supply chain management information systems. RESULTS: Significant correlation was found between the annual consumption and the predictors considered (r=0,879 for CCI; r=0,622 for AP-DRG and r=0,514 for APR-DRG). The CCI corrected by length of stay was the variable that best fit presented (R2=0,863). CONCLUSIONS: The best predictive ability of CCI indicates that resource utilization depends more of the concurrent presence of additional pathology than the case mix calculated for iso resource groups. PMID- 27665763 TI - Nonlinear Carrier Interactions in Lead Halide Perovskites and the Role of Defects. AB - The simple solution processability at room temperature exposes lead halide perovskite semiconductors to a non-negligible level of unintentional structural and chemical defects. Ascertained that their primary optoelectronic properties meet the requirement for high efficiency optoelectronic technologies, a lack of knowledge about the nature of defects and their role in the device operation currently is a major challenge for their market-scale application due to the issues with stability and reliability. Here, we use excitation correlation photoluminescence (ECPL) spectroscopy to investigate the recombination dynamics of the photogenerated carriers in lead bromide perovskites and quantitatively describe the carrier trapping dynamics within a generalization of the Shockley Read-Hall formalism. The superior sensitivity of our spectroscopic tool to the many-body interactions enables us to identify the energetics of the defects. In fact, in the case of polycrystalline films, depending on the synthetic route, we demonstrate the presence of both deep and shallow carrier traps. The shallow defects, which are situated at about 20 meV below the conduction band, dope the semiconductor, leading to a substantial enhancement of the photoluminescence quantum yield despite carrier trapping. At excitation densities relevant for lasing, we observe breakdown of the rate-equation model, indicating a buildup of a highly correlated regime of the photocarrier population that suppresses the nonradiative Auger recombination. Furthermore, we demonstrate that colloidal nanocrystals represent virtually defect-free systems, suffering from nonradiative quenching only due to subpicosecond Auger-like interactions at high excitation density. By correlating the fabrication conditions to the nonradiative loss channels, this work provides guidelines for material engineering towards superior optoelectronic devices. PMID- 27665764 TI - Homogeneous Electrochemical Biosensor for Melamine Based on DNA Triplex Structure and Exonuclease III-Assisted Recycling Amplification. AB - Abasic site (AP site) in the triplex structure can recognize specific target with high selectivity. In this study, this character was first applied to develop a simple, sensitive, and selective homogeneous electrochemical biosensor for melamine determination. The assay combines the advantage of the high selectivity of the DNA triplex structure containing an AP site to melamine and high efficiency of exonuclease (Exo) III-assisted recycling amplification. DNA-1 (T1), DNA-2 (T2), poly[dA] probe containing an AP site (8A) and methylene blue-labeled DNA probe (dMB probe) were carefully designed. Melamine can specifically locate in the AP site through hydrogen bonding interaction between thymine and melamine to make T1, T2, and 8A close to each other, therefore, forming a stable T melamine-T DNA triplex structure. Under the optimal conditions, the differential pulse voltammetric (DPV) response had a linear relationship with the logarithm of melamine concentration in the range of 1 nM~0.5 MUM. The developed biosensor has been successfully applied to detect the migration of melamine from melamine bowl. Result showed that the migration in 4% acetic acid solvent was the largest, which is similar to that detected by high performance liquid chromatography. This homogeneous electrochemical sensor may have a potential prospect in detecting melamine in dairy products and migration of melamine from multicategory food packaging or application materials. PMID- 27665766 TI - Porous Polyrotaxane Coordination Networks Containing Two Distinct Conformers of a Discontinuously Flexible Ligand. AB - A new divergent homopiperazine-derived ligand N,N'-bis(4-carboxyphenyl)-1,4 diazacycloheptane H2L has been prepared, containing a semirigid saturated heterocyclic core which is capable of providing multiple distinct bridging geometries. Reaction of H2L with zinc acetate in DMSO gives a two-dimensional parallel interpenetrated polyrotaxane structure 1 in which the loops and rods are formed by the bent cis-(eq,ax) twist boat and trans-(ax,ax) twist chair conformers, respectively. By matching the distances between the solvated metal sites in the structure of 1, a related material 2 can be prepared incorporating the pillaring ligand trans-1,2-bis(4-pyridyl)ethylene bpe. Compound 2 displays a similar polyrotaxane interpenetration mode, permitted by the presence of both cis and trans ligand conformers, but displays a three-dimensional 2.69 topology related to the dia diamondoid network. The guest exchange and gas adsorption properties of both materials were investigated; while compound 1 displays poor stability to guest exchange and negligible gas uptake, the higher connectivity microporous compound 2 shows facile guest exchange and a surprisingly high CO2 capacity of 12 wt % at 1 bar and 273 K, and a zero-loading enthalpy of adsorption of -32 kJ mol-1. High-pressure adsorption isotherms also show moderate physisorption of H2 and CH4 within the material. PMID- 27665765 TI - Targeting Gliomas: Can a New Alkylating Hybrid Compound Make a Difference? AB - Glioblastoma (GBM) is the most common and aggressive type of brain tumor in adults. The triazene Temozolomide (TMZ), an alkylating drug, is the classical chemotherapeutic agent for gliomas, but has been disappointing against the highly invasive and resistant nature of GBM. Hybrid compounds may open new horizons within this challenge. The multicomponent therapeutic strategy here used resides on a combination of two repurposing drugs acting by different but potentially synergistic mechanisms, improved efficacy, and lower resistance effects. We synthesized a new hybrid compound (HYBCOM) by covalently binding a TMZ analogue to valproic acid, a histone deacetylase inhibitor drug that was shown to sensitize TMZ-resistant glioma cells. Advantages of this new molecule as compared to TMZ, in terms of chemotherapeutic efficacy, were investigated. Our results evidenced that HYBCOM more efficiently decreased the viability and proliferation of the GL261 glioma cells, while showing to better target the tumor cells than the functionally normal astrocytes. Increased cytotoxicity by HYBCOM may be a consequence of the improved autophagic process observed. Additionally, HYBCOM changed the morphology of GL261 cells into a nonpolar, more rounded shape, impairing cell migration ability. Most interesting, and in opposite to TMZ, cells exposed to HYBCOM did not enhance the expression of drug resistance proteins, a major issue in the treatment of GBM. Overall, our studies indicate that HYBCOM has promising chemotherapeutic benefits over the classical TMZ, and future studies should assess if the treatment translates into efficacy in glioblastoma experimental models and reveal clinical benefits in GBM patients. PMID- 27665767 TI - Sodium para-aminosalicylate protected cultured basal ganglia astrocytes from manganese-induced DNA damages and alteration of amino acid neurotransmitter levels. AB - Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 MUM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 MUM PAS-Na treatment for another 24 hr. MnCl2 significantly decreased viability of astrocytes and induced DNA damages via increasing the percentage of tail DNA and Olive tail moment of DNA. Moreover, Mn interrupted amino acid neurotransmitters by decreasing Gln levels and increasing Glu, Gly levels. In contrast, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects on basal ganglia astrocytes. Taken together, our results demonstrated that excessive Mn exposure may induce toxic effects on basal ganglia astrocytes, while PAS-Na could protect basal ganglia astrocytes from Mn-induced neurotoxicity. PMID- 27665768 TI - In utero exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus. AB - Diesel exhaust consists of diesel exhaust particles (DEPs) and gaseous compounds. Because previous research suggested that in utero exposure to DEPs affected spatial learning and memory in male offspring, while epidemiological evidence suggested disturbances in affect after prenatal exposure to particulates, we hypothesized that DEP exposure during pregnancy might also disturb affect. Here, we explored the effects of in utero exposure to DEPs on anxiety in male ICR mice. DEP solutions were administered subcutaneously to pregnant ICR mice at a dose of 0 or 200 MUg/kg body weight on gestation days 6, 9, 12, 15, and 18. We assessed anxiety in 6 week-old male offspring using the hole board test and elevated plus maze test. After the behavioral tests, animals were sacrificed and serotonin (5 HT) levels in the dorsal raphe nucleus (DRN) were measured using HPLC. Mice exposed to DEPs in utero demonstrated increased anxiety in both behavioral tests. HPLC analysis revealed a significant increase in 5-HT levels in the DRN. Double immunolabeling of the DRN using anti-5-HT and anti-FosB (a chronic neuronal activation marker) antibodies indicated chronic activation of the DRN might underlie the increased anxiety after prenatal DEP exposure. PMID- 27665769 TI - Effects of pentobarbital, isoflurane, or medetomidine-midazolam-butorphanol anesthesia on bronchoalveolar lavage fluid and blood chemistry in rats. AB - Bronchoalveolar lavage fluid (BALF) is commonly examined for pulmonary toxicity in animal studies. Two common means of anesthesia before euthanasia and bronchoalveolar lavage in rats are intraperitoneal injection of pentobarbital and inhalation of isoflurane. Medetomidine-midazolam-butorphanol is an alternative anesthesia to pentobarbital for animal welfare; however, the effect of this combination on BALF and blood chemistry is unknown. Here, we compared the effects of anesthesia by intraperitoneal injection of pentobarbital or one of two combinations of medetomidine-midazolam-butorphanol (dose, 0.375-2.0-2.5 or 0.15 2.0-2.5 mg/kg) or by inhalation of isoflurane on BALF and blood chemistry in rats with or without pulmonary inflammation. In BALF, we determined total protein, albumin, lactate dehydrogenase, total cell count and neutrophil count. In serum, we conducted a general chemistry screen. After anesthesia with pentobarbital or isoflurane, there were no significant differences between any of the BALF or blood chemistry parameters with or without inflammation. After anesthesia with either of the combinations of medetomidine-midazolam-butorphanol, lactate dehydrogenase, total cell count, neutrophil count, and almost all of the blood chemistry parameters were comparable with those observed after pentobarbital or isoflurane; however, BALF albumin and serum glucose were significantly increased in rats without inflammation. After the combination of low-dose medetomidine in rats with inflammation, BALF parameters were comparable with those observed after pentobarbital or isoflurane. Our results show that, of the anesthetics examined, inhalation of isoflurane is the most appropriate means of anesthesia when examining BALF or serum for toxicity studies in rats. PMID- 27665770 TI - Usefulness of in vitro combination assays of mitochondrial dysfunction and apoptosis for the estimation of potential risk of idiosyncratic drug induced liver injury. AB - Drug-induced liver injury (DILI) is one of the serious and frequent drug-related adverse events. This adverse event is a main reason for regulatory action pertaining to drugs, including restrictions in clinical indications and withdrawal from clinical trials or the marketplace. Idiosyncratic DILI especially has become a major clinical concern because of its unpredictable nature, frequent hospitalization, need for liver transplantation and high mortality. The estimation of the potential for compounds to induce idiosyncratic DILI is very difficult in non-clinical studies because the precise mechanism of idiosyncratic DILI is still unknown. Recently, many in vitro assays which indicate a possibility of the prediction of the idiosyncratic DILI have been reported. Among these, some in vitro assays focus on the effects of compounds on mitochondrial function and the apoptotic effects of compounds on human hepatocytes. In this study, we measured oxygen consumption rate (OCR) and caspase-3/7 activity as an endpoint of mitochondrial dysfunction and apoptosis, respectively, with human hepatocytes after treatment with compounds causing idiosyncratic DILI (troglitazone, leflunomide, ranitidine and diclofenac). Troglitazone and leflunomide decreased the OCR but did not affect caspase-3/7 activity. Ranitidine increased caspase-3/7 activity but did not affect the OCR. Diclofenac decreased the OCR and increased caspase-3/7 activity. Acetaminophen and ethanol, which are also hepatotoxicants but do not induce idiosyncratic DILI, did not affect the OCR or caspase-3/7 activity. These results indicate that a combination assay of mitochondrial dysfunction and apoptosis is useful for the estimation of potential risk of compounds to induce idiosyncratic DILI. PMID- 27665771 TI - The sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate induces ER stress in human astrocytoma cells. AB - Organophosphorus (OP) compounds such as sarin are toxic agents that irreversibly inhibit the enzyme acetylcholinesterase. A recent study showed that OP compounds also have multiple toxicity mechanisms, and another suggested that endoplasmic reticulum (ER) dysfunction contributes to OP toxicity. However, the signaling pathway and mechanisms involved are poorly understood. We examined whether the sarin-like OP agent bis(isopropyl methyl)phosphonate (BIMP), which exhibits toxicity similar to that of sarin, induced ER stress in human astrocytoma CCF STTG1 cells. Our results demonstrate that BIMP exposure reduced cell viability. Moreover, it induced changes in mitochondrial membrane potential and increased cleavage of caspase 3. Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. Compared to BIMP treatment alone, pretreatment with the CHOP siRNA, siCHOP, decreased BIMP-dependent CHOP expression and improved CCF-STTG1 cell viability. Our findings suggest that BIMP induced mitochondrial dysfunction and apoptotic cell death event mediated by ER stress in CCF-STTG1 cells and that treatment targeted at managing ER stress has the potential to attenuate the toxicity of OP nerve agents. PMID- 27665772 TI - Persistent neuronal apoptosis and synaptic loss induced by multiple but not single exposure of propofol contribute to long-term cognitive dysfunction in neonatal rats. AB - Propofol can induce acute neuronal apoptosis or long-term cognitive dysfunction when exposed at early age in rodents, but it is unclear how the neurotoxicity including neuronal apoptosis and synaptic loss will change in a dynamic manner with brain development after multiple or single exposure of propofol, and the role of neuronal apoptosis and synaptic loss in propofol-induced long-term cognitive impairment needs to be elucidated. In this study, we investigated dynamic changes of neuronal apoptosis, neuronal density, synaptic density in hippocampal CA1 region and the prelimbic cortex (PrL), and long-term cognitive function after multiple or single exposure of propofol in neonatal rats. Results showed that single exposure of propofol only induced great neuronal apoptosis and deficit at postnatal day 9(P9); while multiple exposures of propofol could induce significant neuronal apoptosis, neuronal deficit and synaptic loss at P9, P14, P21, or P35 compared with intact, and spatial learning and memory impairment from P36 to P41. Results suggest that single exposure of propofol only induces transient neuronal apoptosis and deficit, while multiple exposures of propofol induce persistent neuronal apoptosis, neuronal deficit, synaptic loss, and long term cognitive impairment. Furthermore, persistent neuronal deficit and disturbances in synapse formation but not transient neuronal apoptosis may contribute to long-term cognitive impairment. PMID- 27665773 TI - Body surface area measurement in laboratory miniature pigs using a computed tomography scanner. AB - The body surface area (BSA) of an organism is an important parameter for evaluating physiological functions. In drug development, normalization by BSA is an appropriate method for extrapolating doses between species. The BSA of animals has generally been estimated by multiplying a constant by the power of the body weight (BW). Recently, the use of miniature pigs in non-clinical studies for medical drugs or devices has gradually been increasing. However, verification of their BSA is not as yet sufficient. In this study, we measured the BSAs of 40 laboratory miniature pigs (11 males and 9 females of Gottingen minipig and 14 males and 6 females of Nippon Institute for Biological Science [NIBS] miniature pig) by analyzing computed tomography (CT) images, since measurements using a CT scanner were expected to more precisely determine BSA than classical measuring techniques. The measurement results showed the BSAs of the 20 Gottingen minipigs to range from 0.4358 to 0.8356 m(2) (the working BW range: 12.7-37.0 kg) and 20 NIBS miniature pigs to range from 0.2906 to 0.8675 m(2) (the working BW range: 7.9-41.5 kg). Since accuracy and reproducibility were confirmed by measuring the surface area of an acrylic cuboid, we concluded the measurement method employed in this study to be very reliable. We propose the following estimating formula for BSA of laboratory miniature pigs: 100 * BSA [m(2)] = 7.98 * BW [kg](2/3). PMID- 27665774 TI - Hydrogen sulfide donor NaHS induces death of alveolar epithelial L2 cells that is associated with cellular shrinkage, transgelin expression and myosin phosphorylation. AB - Hydrogen sulfide (H2S) is a highly toxic gaseous molecule that causes death to humans exposed to high concentrations. H2S is absorbed into the body through the alveolar epithelium and other tissues. The aim of this study is to evaluate the molecular mechanism underling acute lung injury caused by the inhalation of high concentrations of H2S. Rat lung epithelium-derived L2 cells were exposed to a H2S donor, NaHS, at concentrations of 2-4 mM for 1-6 hr. NaHS caused shrinkage and death of the cells without caspase activation. An actin-binding protein, transgelin, was identified as one of the NaHS-inducible proteins in the cells. NaHS increased myosin light chain (MLC) phosphorylation, indicating that actomyosin-mediated cellular contractility and/or motility could be increased after NaHS exposure. The administration of ML-7, a myosin light chain kinase (MLCK) inhibitor, accelerated cell death after NaHS exposure. Based on these data, we conclude that the increase in MLC phosphorylation in response to NaHS exposure is a cellular protective reaction against NaHS toxicity. Enhancements in smooth muscle cell properties such as transgelin expression and actomyosin mediated contractility/motility might be involved in cell survival after NaHS exposure. PMID- 27665775 TI - Exposure time-dependent thermal effects of radiofrequency electromagnetic field exposure on the whole body of rats. AB - We investigated the thermal effects of radiofrequency electromagnetic fields (RF EMFs) on the variation in core temperature and gene expression of some stress markers in rats. Sprague-Dawley rats were exposed to 2.14 GHz wideband code division multiple access (W-CDMA) RF signals at a whole-body averaged specific absorption rate (WBA-SAR) of 4 W/kg, which causes behavioral disruption in laboratory animals, and 0.4 W/kg, which is the limit for the occupational exposure set by the International Commission on Non-Ionizing Radiation Protection guideline. It is important to understand the possible in vivo effects derived from RF-EMF exposures at these intensities. Because of inadequate data on real time core temperature analyses using free-moving animal and the association between stress and thermal effects of RF-EMF exposure, we analyzed the core body temperature under nonanesthetic condition during RF-EMF exposure. The results revealed that the core temperature increased by approximately 1.5 degrees C compared with the baseline and reached a plateau till the end of RF-EMF exposure. Furthermore, we analyzed the gene expression of heat-shock proteins (Hsp) and heat-shock transcription factors (Hsf) family after RF-EMF exposure. At WBA-SAR of 4 W/kg, some Hsp and Hsf gene expression levels were significantly upregulated in the cerebral cortex and cerebellum following exposure for 6 hr/day but were not upregulated after exposure for 3 hr/day. On the other hand, there was no significant change in the core temperature and gene expression at WBA-SAR of 0.4 W/kg. Thus, 2.14-GHz RF-EMF exposure at WBA-SAR of 4 W/kg induced increases in the core temperature and upregulation of some stress markers, particularly in the cerebellum. PMID- 27665776 TI - The effects of early postnatal exposure to a low dose of decabromodiphenyl ether (BDE-209) on serum metabolites in male mice. AB - The toxicity of decabromodiphenyl ether (BDE-209) has been reported in several studies. However, there is not much known about the toxicological biomarkers that characterize BDE-209 exposure. In this study, we subcutaneously exposed mice to 0.025 mg/kg/day BDE-209 on postnatal days 1-5 and sacrificed the animals at 12 weeks of age (day 84). Flow injection analysis and hydrophilic interaction chromatography-triple quadrupole mass spectrometry were used to determine the serum metabolomes of these mice in order to characterize the effects of BDE-209 exposure. Data analysis showed a good separation between control and exposed mice (R(2) = 0.953, Q(2) = 0.728, and ANOVA of the cross-validated residuals (CV ANOVA): P-value = 0.0317) and 54 metabolites were identified as altered in the exposed animals. These were selected using variable importance (VIP) and loadings scaled by a correlation coefficient criteria and orthogonal partial least squares discriminant analysis (OPLS-DA). BDE-209-exposed mice showed lower levels of long chain acylcarnitines and citrate cycle-related metabolites, and higher levels of some amino acids, long-chain phospholipids, and short-chain acylcarnitines. The disruption of fatty acid, carbohydrate, and amino acid metabolism observed in the serum metabolome might be related to the previously observed impaired spermatogenesis in mice with early postnatal exposure to a low dose of BDE-209. PMID- 27665777 TI - Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARalpha activities. AB - The oxidative, reductive, and hydrolytic metabolism of methiocarb and the hydrolytic metabolism of carbaryl by liver microsomes and plasma of rats or humans were examined. The effects of the metabolism of methiocarb and carbaryl on their nuclear receptor activities were also examined. When methiocarb was incubated with rat liver microsomes in the presence of NADPH, methiocarb sulfoxide, and a novel metabolite, methiocarb sulfone were detected. Methiocarb sulfoxide was oxidized to the sulfone by liver microsomes and reduced back to methiocarb by liver cytosol. Thus, the interconversion between methiocarb and the sulfoxide was found to be a new metabolic pathway for methiocarb by liver microsomes. The product of methiocarb hydrolysis, which is methylthio-3,5-xylenol (MX), was also oxidized to sulfoxide form by rat liver microsomes. The oxidations were catalyzed by human flavin-containing monooxygenase isoform (FMO1). CYP2C19, which is a human cytochrome P450 (CYP) isoform, catalyzed the sulfoxidations of methiocarb and MX, while CYP1A2 also exhibited oxidase activity toward MX. Methiocarb and carbaryl were not enzymatically hydrolyzed by the liver microsomes, but they were mainly hydrolyzed by plasma and albumin to MX and 1 naphthol, respectively. Both methiocarb and carbaryl exhibited PXR and PPARalpha agonistic activities; however, methiocarb sulfoxide and sulfone showed markedly reduced activities. In fact, when methiocarb was incubated with liver microsomes, the receptor activities were decreased. In contrast, MX and 1-naphthol showed nuclear receptor activities equivalent to those of their parent carbamates. Thus, the hydrolysis of methiocarb and carbaryl and the oxidation of methiocarb markedly modified their nuclear receptor activities. PMID- 27665778 TI - Transcriptome analyses demonstrate that Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) activity of an ultraviolet absorber, 2-(2'-hydroxy 3',5'-di-tert-butylphenyl)benzotriazole, as possible mechanism of their toxicity and the gender differences. AB - 2-(2'-Hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), the Benzotriazole UV-stabilizer (BUVSs) known as UV-320, is widely used in plastic materials for protection against UV-irradiation. Previously, we reported that oral ingestion of HDBB induce hepatotoxicity including hepatocyte hypertrophy and necrosis in rats and, males was more susceptible compared with females in young rats while no sex related difference was observed in preweaning rats. Phenotypes observed in our previous study imply involvement of peroxisome proliferator-activated receptor (PPAR) alpha in HDBB hepatotoxicity, however, direct evidence that HDBB can activate PPARalpha has not been provided and the mechanism which underlying the gender difference of HDBB hepatotoxicity was not clearly elucidated. Here, we conduct transcriptome analysis using microarray expression profiles in the livers of rats administered HDBB. PPARalpha agonist activity of HDBB was elucidated by comparison with gene expression data of typical PPARalpha agonist, i.e. clofibrate, WY-14643, gemfibrozil, and fenofibrate, from TG GATEs database. Moreover, we analyzed for PPARalpha mRNA expression in the liver of developing male and female rats. PPARalpha mRNA expression level was higher in males than in females on postnatal days (PNDs) 28 and 35, whereas no sex-related difference was found on PNDs 7 and 22. These results suggest that HDBB exerts its hepatotoxicity through the PPARalpha signal pathway and the sex-related difference in PPARalpha expression may contribute to the sex-related difference in susceptibility to hepatotoxicity. PMID- 27665779 TI - N-methyl pyrrolidone (NMP) ameliorates the hypoxia-reduced osteoblast differentiation via inhibiting the NF-kappaB signaling. AB - Ischemic-hypoxic condition for local osteoblasts and bone mesenchymal stem cells during bone fracture inhibits bone repairing. N-methyl pyrrolidone (NMP) has been approved as a safe and biologically inactive small chemical molecule, and might be useful for bone fracture repairing. In the present study, we investigated the effect of NMP on the hypoxia-reduced cellular viability and the expression of differentiation-associated markers, such as bone morphogenetic protein 2 (BMP-2), propeptide of type I procollagen I (PINP), alkaline phosphatase (ALP) or runt related transcription factor 2 (Runx2) in the osteoblasts, and then we examined the molecular mechanism underlining such effect in the human osteoblastic hFOB 1.19 cells. Our results demonstrated that NMP significantly blocked the hypoxia induced cell viability reduction and inhibited the hypoxia-caused expression downregulation of BMP-2, PINP, ALP and Runx2 in hFOB 1.19 cells. Then we confirmed the involvement of nuclear factor kappaB (NF-kappaB) pathway in the regulation by NMP on the hypoxia-mediated the reduction of osteoblast differentiation. The upregulated expression and transcriptional activity of NF kappaB, while the downregulated inhibitory kappaB expression by the hypoxia treatment was reversed by the treatment with 10 mM NMP. In conclusion, our study found a protective role of NMP in osteoblast differentiation in response to hypoxia, and such protection was through inhibiting the NF-kappaB signaling. This suggests that NMP might be a protective agent in bone fracture repairing. PMID- 27665780 TI - Platelet-rich plasma protects rat chondrocytes from interleukin-1beta-induced apoptosis. AB - Interleukin (IL)-1beta-induced chondrocyte apoptosis is associated with the pathogenesis of arthritis. Platelet-rich plasma (PRP), which is derived from the patient's own blood and contains numerous growth factors, has the potential for arthritis treatment. Therefore, the present study aimed to determine the effects of PRP on chondrocyte apoptosis, under IL-1beta-induced pathological conditions. Chondrocytes isolated from the knee joint of Sprague Dawley rats were used in the present study. Cell viability was determined using the Cell Counting kit-8 assay, cell apoptosis was evaluated by flow cytometry, and the expression of apoptosis-, anabolism- and catabolism-associated genes were detected by quantitative polymerase chain reaction; protein expression was detected by western blot analysis. The results demonstrated that 10% PRP in the culture medium increased chondrocyte proliferation, whereas IL-1beta induced cell apoptosis. Treatment with PRP significantly attenuated cell apoptosis in IL-1beta-treated chondrocytes, and altered apoptosis-associated expression at the gene and protein level. Furthermore, treatment with PRP significantly reduced matrix metalloproteinase production and promoted anabolism of cartilage extracellular matrix under IL-1beta treatment. The present study demonstrated the protective effects of PRP on chondrocyte apoptosis and extracellular matrix anabolism, and provided scientific evidence to support the potential use of PRP as a promising therapeutic strategy for the treatment of arthritis. PMID- 27665781 TI - Flow cytometric analyses of the viability, surface marker expression and function of lymphocytes from children following cryopreservation. AB - Flow cytometric analysis is important for the investigation and clinical preparation of lymphocytes from children. However, the strict requirement of cell freshness and inter-assay variability limits the application of this methodology for pediatric investigations. Therefore, it is necessary to identify a reliable cryopreservative method capable of maintaining high cell viability and proper cell function in lymphocytes from children. In the present study, eight commonly used cell cyropreservative methods were used, and their effects on cell viability, surface marker expression and cell function were examined. In addition, how these methods affect the distribution of T-cell receptor Vbeta subfamilies were also determined. The results of the present study provided valuable experimental evidence, based on which the optimal method for the cryopreservation of lymphocytes from children in pediatric investigations and clinical applications can be selected. PMID- 27665782 TI - Sclerostin expression in the subchondral bone of patients with knee osteoarthritis. AB - The aim of this study was to assess the expression of beta-catenin, transcription factor-4 (TCF-4) and sclerostin in the subchondral bone of patients with primary knee osteoarthritis (OA). Tibial plateau specimens from patients with OA who underwent total knee arthroplasty were classified into the early stage (n=15), intermediate stage (n=13) and late stage (n=17) groups using the Mankin score. Structural parameters, including total articular cartilage (TAC), subchondral bone plate (SCP) thickness and trabecular bone volume (BV/TV), were assessed using Image-Pro Plus 6.0 analysis software. Subsequently, beta-catenin and sclerostin expression levels in subchondral bone were determined by immunohistochemistry. In addition, the mRNA and protein levels of beta-catenin, TCF-4 and sclerostin were evaluated by RT-qPCR and western blot analysis, respectively. As regards the cartilage and subchondral bone structural parameters, TAC was reduced, while SCP thickness and BV/TV were increased due to OA, with significant differences observed among the different stages (all P<0.05). The results of immunohistochemistry revealed that the beta-catenin levels in the intermediate- and late-stage samples were significantly increased, while the levels of sclerostin were markedly decreased compared with the values in the early-stage samples (all P<0.05). Compared with the intermediate-stage samples, the sclerostin levels were decreased, and SCP thickness and the beta catenin levels were increased in the late-stage samples (all P<0.05). The results of RT-qPCR and western blot analysis revealed that the beta-catenin and TCF-4 mRNA and protein levels in the intermediate- and late-stage samples were significantly increased, while sclerostin expression was significantly decreased compared with the early-stage samples; a similar trend was observed between the intermediate- and late-stage samples (all P<0.05). Finally, the beta-catenin and TCF-4 levels positively correlated with the Mankin scores, while there was a negative correlation with sclerostin expression. Our findings demonstrate that sclerostin expression is closely associated with the degree of joint damage in patients with OA, confirming its involvement in the development of OA. PMID- 27665783 TI - Meiotic cohesin subunits RAD21L and REC8 are positioned at distinct regions between lateral elements and transverse filaments in the synaptonemal complex of mouse spermatocytes. AB - Cohesins containing a meiosis-specific alpha-kleisin subunit, RAD21L or REC8, play roles in diverse aspects of meiotic chromosome dynamics including formation of axial elements (AEs), assembly of the synaptonemal complex (SC), recombination of homologous chromosomes (homologs), and cohesion of sister chromatids. However, the exact functions of individual alpha-kleisins remain to be elucidated. Here, we examined the localization of RAD21L and REC8 within the SC by super-resolution microscopy, 3D-SIM. We found that both RAD21L and REC8 were localized at the connection sites between lateral elements (LEs) and transverse filaments (TFs) of pachynema with RAD21L locating interior to REC8 sites. RAD21L and REC8 were not symmetrical in terms of synaptic homologs, suggesting that the arrangement of different cohesins is not strictly fixed along all chromosome axes. Intriguingly, some RAD21L signals, but not REC8 signals, were observed between unsynapsed regions of AEs of zygonema as if they formed a bridge between homologs. Furthermore, the signals of recombination intermediates overlapped with those of RAD21L to a greater degree than with those of REC8. These results highlight the different properties of two meiotic alpha-kleisins, and strongly support the previous proposition that RAD21L is an atypical cohesin that establishes the association between homologs rather than sister chromatids. PMID- 27665784 TI - alpha-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. AB - Oxidative stress appears to be a central event responsible for the degeneration of dopaminergic neurons in Parkinson's disease (PD). 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine or its toxic metabolite 1-methyl-4-phenylpyridinium (MPP+) are classical widely-used pharmacological and toxic agents to model PD; they cause the production of reactive oxygen species by inhibiting mitochondrial complex I, leading to DNA oxidative damage and subsequent neuronal death. Previous findings have suggested that proliferating cell nuclear antigen (PCNA), a critical regulatory protein for DNA repair, is involved in dopaminergic neuron damage in the MPP+-induced PD model. The naturally occurring dithiol compound, alpha-lipoic acid (ALA) has been reported to provide neuroprotection in in vitro models of PD. The molecular mechanism by which ALA reduces neuronal death in PD remains to be fully elucidated. The present study aimed to analyze the ability of ALA to protect neuronal PC12 cells from the toxicity induced by MPP+, and the molecular mechanism underlying these actions using MTT and lactate dehydrogenase cytotoxicity assays, Hoechst 33258 staining and western blot analysis. The results demonstrated that ALA efficiently increased the production of PCNA in MPP+-treated PC12 cells. Accordingly, ALA treatment attenuated MPP+-induced toxicity in the PC12 cells, and reduced cell apoptosis. The increase in the expression levels of PCNA by ALA in the MPP+-treated PC12 cells appeared to be mediated by repression of the p53 protein, as the expression of p53 was increased by MPP+-treatment and reduced by ALA. Taken together, these results indicated that ALA protected dopaminergic neurons against MPP+-induced neurotoxicity through its ability to upregulate the DNA repair protein, PCNA, via the P53 pathway. PMID- 27665786 TI - Study days. AB - North May 11 Barrow in Furness Venue: Lecture Theatre, Furness General Hospital, Abbey Road, Barrow in Furness Contact: Sue Askew, District Infection Control Nurse, Furness General Hospital. Tel: 0229 870070 Ext 3021. PMID- 27665787 TI - Tissue viability society. AB - The Tissue Viability Society, founded in 1981 as a branch of the Wessex Rehabilitation Association, was originally concerned with the prevention and healing of pressure sores. It has developed as a unique forum for considering all aspects of the problems of tissue viability. PMID- 27665785 TI - Arsenic trioxide potentiates the effectiveness of etoposide in Ewing sarcomas. AB - Ewing sarcomas (ES) are rare mesenchymal tumours, most commonly diagnosed in children and adolescents. Arsenic trioxide (ATO) has been shown to efficiently and selectively target leukaemic blasts as well as solid tumour cells. Since multidrug resistance often occurs in recurrent and metastatic ES, we tested potential additive effects of ATO in combination with the cytostatic drugs etoposide and doxorubicin. The Ewing sarcoma cell lines A673, RD-ES and SK-N-MC as well as mesenchymal stem cells (MSC) for control were treated with ATO, etoposide and doxorubicin in single and combined application. Viability and proliferation (MTS assay, colony formation, 3D spheroid culture) as well as cell death induction (western blot analysis, flow cytometry) were analysed. In the MTS viability assays ATO treatment significantly reduced the metabolic activity of all three ES cell lines (A673, RD-ES and SK-N-MC) examined. Moreover, all ES cell lines were sensitive to etoposide, whereas MSC remained unaffected by the drug concentrations used. With the exception of ATO in RD-ES cells, all drugs induced apoptosis in the ES cell lines, indicated by caspase-3 and PARP cleavage. Combination of the agents potentiated the reduction of viability as well as the inhibitory effect on clonal growth. In addition, cell death induction was obviously enhanced in RD-ES and SK-N-MC cells by a combination of ATO and etoposide compared to single application. Summarised, the combination of low dose, physiologically easily tolerable ATO with commonly used etoposide and doxorubicin concentrations efficiently and selectively suppressed viability and colony formation in ES cell lines, whereas a combination of ATO and etoposide was favourable for cell death induction. In addition to an increase of the effectiveness of the cytostatic drugs and prevention of potential drug resistance, this approach may also reduce toxicity effects, since the individual doses can be reduced. PMID- 27665788 TI - Reaping long-term rewards. AB - It can be hard to find something to celebrate in nursing. Bad news travels faster than good and invariably receives more coverage. The problem stems from perceived news values that dictate a constant fodder of doom and gloom. And there's no shortage of that in the health services at present. But, between announcements about further redundancies and cuts, last week's Clinical Practice and Management Awards offered a glimmer of hope to would-be nurse managers. PMID- 27665789 TI - Pressure sore risk in operating theatres. AB - Little information is available on the genesis of intraoperative pressure sores. A pilot study was set up to investigate whether it is necessary, to prevent pressure sores developing in the operating department. Skin assessments and Braden score readings were taken pre-operatively and post-operatively. Half of the 26 patients had skin changes pre-operatively and there was a 'theatre generated incidence of 12.5 per cent. The author concludes that further investigation should be commenced. PMID- 27665790 TI - Union outrage at anti-strike plans. AB - 'Draconian' government proposals to limit strike action by nurses and other public sector employees represent a fundamental attack on the rights of the individual, angry health unions claimed last week. PMID- 27665791 TI - Nursing strategy too politically biased? AB - The Department of Health is launching its new Strategy for Nursing this week, amid claims that the document is too politically biased. PMID- 27665792 TI - New Award winners show nurses are 'natural leaders'. AB - Nurses are natural leaders and managers, Health Secretary Virginia Bottomley said last week at a ceremony for the winners of the first Clinical Practice and Management Training Awards. PMID- 27665794 TI - Threat to close Yorkshire hospital. AB - A north Yorkshire Trust is L1.5 million in the red and is set to close a Scarborough hospital, health unions claimed last week. PMID- 27665793 TI - Unions warn against nurses used as 'surgeon's assistants'. AB - Nurses should not be left to do dull, repetitive jobs which junior doctors want to avoid, unions warned last week, as a new report backed the use of nurses as surgeon's assistants. PMID- 27665795 TI - ? AB - Former RCN President Dame Sheila Quinn (left) has been chosen to receive nursing's most prestigious prize, the Christine Reimann Award, presented every four years by the ICY Dante Sheila, pictured with Anne Baillie, matron at a Brendoncare home, attends a reception hosted by the Brendoncare Foundation to acknowledge the prize she will receive in June. PMID- 27665797 TI - Call to review legislation against kerb-crawling. AB - Laws which ban kerb-crawling should be reviewed in an attempt to lessen the health risks to women who prostitute, RCN Council members agreed last week. PMID- 27665796 TI - Nurses are not always as busy as they think, claims university lecturer. AB - Nurses are not as busy as they sometimes think, one of the authors of a report on staffing levels and standards of care claimed last week. PMID- 27665799 TI - Medic training encouraged for nurses. AB - Nursing graduates should be offered cash incentives to train as doctors, a new report from the Centre for Health Economics recommends. PMID- 27665798 TI - RCN guidance strengthens value of ENs. AB - The RCN is to strengthen its policy on enrolled nurses by encouraging employers not to place adverts for clinical positions which discriminate against second level nurses. PMID- 27665800 TI - 17 per cent of home helps claim they do nurses' tasks. AB - Almost one in five home helps is carrying out nursing tasks such as changing dressings, bathing clients or administering medicines, according to a new survey. PMID- 27665801 TI - ? AB - Stepping out: Five year old Stuart Rayfield tries out computerised equipment at the new Gait Laboratory at the Robert Jones & Agnes Hunt Orthopaedic Hospital in Shropshire. The laboratory, the first in the UK, has special facilities for people with cerebral palsy. PMID- 27665802 TI - More help for school nursing. AB - Labour MPs are calling on the Government to provide more help for school nursing, after an RCN survey showed spending cuts are hitting the service. More than 20 MPs have urged Health Secretary Virginia Bottomley to find ways to improve the service and ensure every pupil has access to a named school nurse. PMID- 27665803 TI - Fear 'cost cutting' in agency nurse skills. AB - Hospitals may be taking on temporary nurses on lower grades to cut costs, the RCN warned last week, after a Labour MP complained agency staff with insufficient experience were being employed on specialist wards. PMID- 27665804 TI - Understanding the meaning of woundsLittle research has been done to address patients' understanding of wounds and bow that might interfere with treatment and healing. This article tackles the issue by examining the meaning of wounds to patients ( 1 ). The origin of the wound and the patients' environment can make a difference to how patients view treatment and healing. The author identifies how this knowledge can be incorporated into nurses' assessment of wounds. AB - Words such as community, wound and care can hold very different meanings for people involved in the NHS. In the hospital setting, the environment of the patient is made as similar as possible in terms of space, lockers and bed so their own context is suspended temporarily and compliance in recommended treatment is very high. At home, however, the difficulties facing community nurses in terms of defining the problem, controlling the environment and compliance are well known ( 2 ). PMID- 27665805 TI - Nursing Standard congratulates Clinical Practice and Management the winners of the Training Awards. AB - The Award winners, pictured, were presented with their certificates by tiie Secretary of State for Health Virginia Bottomley and Mr John Robinson, Chief Executive of Smith tk Nephew pic, at a special awards luncheon in London last week. These 12 nurses were chosen from the hundreds of entries received for the Clinical Practice and Management Awards, a joint initiative between the RCN, Smith & Nephew Medical and Nursing Standard. Entrants had to read all ten articles in the Clinical Practice and Management Series which appeared in Nursing Standard, answer multiple choice questions at the end of each - then write a 1,000 word essay on how they would like to further their management skills or how the series of articles helped them in their practice. In addition to the 12 finalists over 300 nurses received a special certificate to verify they had completed the series and answered the questions correctly. This week the winners are attending an expenses paid, residential management training course at Sundridge Park Management College in Kent. PMID- 27665807 TI - Leg ulcers can 'seriously disrupt' lives. AB - Leg ulcers can seriously disrupt the lives of elderly patients, resulting in low levels of satisfaction and significant depression. PMID- 27665808 TI - Mattress covers assessed for pressure. AB - Nurses should ensure all standard mattress covers are replaced with a light cover to reduce the risk of pressure sores developing, a leading expert, Dr Ian Swain from Salisbury's Odstock hospital, told delegates at the conference at Liverpool University. PMID- 27665809 TI - Counselling for crisis and strain. AB - Nurses should see crises and strain as a challenge rather than always seeing them negatively, a National Association for Staff Support conference heard last week. PMID- 27665810 TI - Study finds sinus packing should be abandoned. AB - Patients suffer considerable pain during packing of sinuses and the procedure should be abandoned in favour of irrigation, a pilot study has found. PMID- 27665812 TI - MP calls for global action on health. AB - Industrialised nations must do more to tackle ill-health in developing countries, shadow health secretary David Blunkett has said. PMID- 27665811 TI - 'Throw pressure sore tracings in the bin'. AB - Tracings of pressure sores to assess their change in size should be 'thrown in the bin', says computer officer, Dr Denis Anthony. PMID- 27665813 TI - Ultrasound screening for ovarian cancer. AB - Ovarian cancer in women with a family history of the disease can be detected early using an ultrasound screening method, researchers have found. PMID- 27665815 TI - Nurses could improve their knowledge of MS. AB - Few people with multiple sclerosis (MS) see nurses as a good source of information about the disease, although most expect a clear explanation of their symptoms, according to a report from the British Society of Rehabilitation Medicine. PMID- 27665814 TI - Survey shows benefits of breast screening. AB - Deaths from breast cancer can be reduced by at least a quarter through regular screening and follow-up, a survey has found. PMID- 27665816 TI - Manufacturers have effect on listeriae. AB - Changes in food manufacturing and/or health education measures may have had an impact on the epidemiology of infections with Listeria monocytogenes, researchers from Leicester say. PMID- 27665817 TI - Improving the diet of children under five. AB - Intervention by the primary health care team may improve the diet of vulnerable groups, researchers suggest. PMID- 27665818 TI - Prevention of type I diabetes achievable? AB - Prevention of type I diabetes is now a practical goal, according to research. PMID- 27665819 TI - Better targeting needed for influenza vaccine. AB - Improved targeting and education is needed to increase immunisation against influenza in people at risk. PMID- 27665820 TI - Transdermal oestrogen and exercise don't mix. AB - Women on transdermal hormone replacement therapy may be well advised to remove their patches before undertaking vigorous exercise. PMID- 27665821 TI - Health care afloat. AB - A unique floating hospital, dedicated to providing free healthcare for developing countries, is due to spend 11 weeks in four United Kingdom ports recruiting nursing and medical staff and procuring supplies for its next voyage to Senegal. PMID- 27665822 TI - Buying in good faith. AB - Health service purchasing teams would be 'seriously flawed' without a member with a nursing background, a government report has warned. It says clinical nurses should be encouraged to move into purchasing as part of a recognised career path and argues that nurses have an extensive' contribution to make in this area. 'The Professional Nursing Contribution to Purchasing', produced by the King's Fund College for the National Health Service Management Executive, says nurses are starting to have a major input into purchasing after a 'slow start'. PMID- 27665823 TI - Time to get off your knees. AB - I have just read that the government is considering plans to allow Trusts to become completely run by private companies (Hospitals should be run by the private sector, News, April 21). What a disgrace. PMID- 27665824 TI - Project 2000 - the continuing story. AB - After reading Max Binns' letter (Putting students in their placement, April 7), 1 began to wonder whether my colleagues and I are the only Project 2000 students who are being welcomed into workplaces by the vast majority of healthcare workers they encounter. PMID- 27665825 TI - ? AB - *When are we as nurses, as a society, going to stand up to the disciples of market forces and tell them that enough is enough? PMID- 27665827 TI - ? AB - *Many of the 'I am a Project 2000 student' letters I have read recently have complained of the treatment that trained staff and 'traditional' students have meted out to the authors. PMID- 27665826 TI - Information exchange. AB - * The RCN Association for Care of the Elderly's national executive committee would like to discover how much interest there would be from members in the possible formation of a special interest group for continuing care nurses. This would aim to provide professional leadership, guidance and support. PMID- 27665828 TI - ? AB - Oh dear, not another one. Perhaps Max Binns and Project 2000 students like him should put down their torches and just get on with being nursing students. PMID- 27665829 TI - The Clay column. AB - I hope the community care changes introduced on April Fool's Day do not make fools of us all. PMID- 27665831 TI - Introducing Quality Assurance into the NHS Introducing Quality Assurance into the NHS Gould T Macmillan H Merrett 76pp L9.99 0-333-57061-8. AB - The subtitle of this book Introducing Quality Assurance into the NHS: Practical Experience from Wandsworth Continuing Care Unit most accurately reflects the tone of the work. PMID- 27665832 TI - Paterson and Zderad Paterson and Zderad N O'Connor SAGE 64pp L6.50 0-8039-4489-6. AB - Paterson and Zderad is the seventh in the series 'Notes on Nursing Theories'. Paterson and Zderad are both now retired, but spent considerable time developing and teaching the humanistic nursing theory underlying their model. PMID- 27665833 TI - The name game initiative. AB - Hi there, health care workers. Another first for my New Nursing Unit - the head of our clinical directorate told me this week that it is to be the first on his list for a quality review. Of course, he wants to start in the area with the highest standards. PMID- 27665834 TI - Homoeopathy. AB - Whilst many areas of life in Britain have been affected by the recession, growth within the natural medicine sector has continued unabated and public awareness of optional systems of healthcare has steadily increased. With its Royal patronage and widespread use in domestic life, homoeopathy has been one of the leading therapies to benefit from this growth. PMID- 27665835 TI - Career listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27665836 TI - Low-dose lenalidomide and dexamethasone combination treatment in elderly patients with relapsed and refractory multiple myeloma. AB - OBJECTIVE: This study investigated the efficacy and safety of low-dose lenalidomide combined with dexamethasone in elderly patients with relapsed and refractory multiple myeloma (MM). METHODS: Thirty-two elderly patients with refractory and recurrent MM (median age: 64 years) were treated with low-dose lenalidomide (LD-R) combined with dexamethasone (D). LD-R (10 mg/d) was administered orally for 21 days and D (40 mg/d) was administered twice a day on days 1-4, 9-12, and 17-20. The treatment lasted 2-8 28-day cycles. RESULTS: After two cycles, the complete, very good partial, and partial remission rates were 12.5% (4/32), 25.0% (8/32), and 34.4% (11/32), respectively. The overall response rate was 71.9% (23/32). After a 24-month follow-up, 23 patients responded to therapy, three were in complete remission, four were stable, and 16 exhibited disease progression. In addition, median time-to-progression was 13 months. Observed side effects were hypodynamia, gastrointestinal reaction, peripheral neuritis, and mild hypocytosis. CONCLUSION: Low-dose lenalidomide in combination with dexamethasone is an effective and safe treatment for relapsed and refractory MM in elderly patients. PMID- 27665838 TI - Contemporary molecular tests for prognosis and treatment guidance for castration resistant prostate cancer. AB - INTRODUCTION: Currently, clinical factors related to the malignancy and patient related factors such as performance status and comorbidities are employed to select agents to treat metastatic castration resistant prostate cancer (mCRPC). Areas covered: This paper covers emerging molecular panels that may be used in the clinic as prognostic or predictive biomarkers to treat mCRPC. Expert commentary: The expression of androgen receptor variant (AR-V)-7 in circulating tumor cells appears especially promising to select patients for taxane chemotherapy versus androgen inhibitors, abiraterone and enzalutamide. Additionally, the presence of DNA repair alterations such as BRCA alterations are rapidly emerging as a predictive biomarker to develop precision medicine using PARP inhibitors for these patients. PMID- 27665837 TI - Corrosion resistance of biodegradable Mg with a composite polymer coating. AB - Degrading Mg and its alloys are a category of implant materials for bone surgery, but rapid corrosion in physiological environment limits their clinical applications. To improve the corrosion resistance of Mg-based implants, a biodegradable composite polymer coating is deposited on an Mg rod in this work. The strategy is to decorate Mg surfaces with poly(gamma-glutamic acid)-g-7-amino 4-methylcoumarin/hydroxyapatite (gamma-PGA-g-AMC/HAp) composite nanoparticles through electrophoretic deposition in ethanol. The morphology and chemical composition of the resulting coating material are determined by scanning electron microscopy and Fourier transform infrared spectroscopy. Sample rods of bare Mg and coated Mg are implanted intramedullary into the femora of New Zealand white rabbits, periodic radiography and post-autopsy histopathology of each sample are analyzed. The obtained in vivo results clearly confirm that the coating material decreases degradation rate of the underlying Mg sample and appears good histocompatibility and osteoinductivity. The main aim of this work is to investigate the degradation process of bare Mg and coated Mg samples in bone environment and their effect on the surrounding bone tissue. PMID- 27665839 TI - Analytical progresses of the World Anti-Doping Agency Olympic laboratories: a 2016 update from London to Rio. AB - The 2016 Olympic and Paralympic Games, the biggest event in human sports, was held in Rio de Janeiro with more than 10,500 athletes from 206 countries over the world competing for the highest of sports honors, an Olympic medal. With the hope that the Olympic ideal accompanies all aspects of the XXXI Olympiad, WADA accredited antidoping laboratories use the spearhead of analytical technology as a powerful tool in the fight against doping. This review summarizes the main analytical developments applied in antidoping testing methodology combined with the main amendments on the WADA regulations regarding analytical testing starting from the 2012 London Olympics until the 2016 Olympic Games in Rio de Janeiro. PMID- 27665840 TI - Psychiatry and the dying prisoner. AB - Due to the growing number of ageing prisoners in the American correctional system, penal institutions are increasingly caring for patients with chronic and potentially terminal medical conditions. To address this problem states have attempted sentencing reform initiatives and adopted compassionate release programmes; however, these efforts have failed to significantly reduce the number of elderly or seriously ill inmates. Correctional mental health services are now called upon to aid in the care of prisoners at the end of life. This article presents the common elements of prison hospice programmes and the role psychiatry plays in this multidisciplinary effort. The right-to-die movement holds future implications for correctional mental health professionals. The historical and legal background of this international movement is presented with particular attention given to landmark cases and statutes protecting institutionalized patients. PMID- 27665841 TI - Measurement properties of the Arm Function in Multiple Sclerosis Questionnaire (AMSQ): a study based on Classical Test Theory. AB - PURPOSE: The construct validity, test-retest reliability, and measurement error of the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) were examined. Additionally, the influence of administration-method on reliability and measurement error was investigated. METHOD: 112 Dutch adult MS-patients from an academic- and a residential care-facility participated. Questionnaires were administered on paper, online or as interview, and patients performed several performance tests. Construct validity was assessed by testing pre-defined hypotheses. Reliability was assessed using Intraclass Correlation Coefficients (ICCs), Standard Error of Measurements (SEMs) and Smallest Detectable Changes (SDCs). RESULTS: For construct validity (N = 105) 9 of 13 hypotheses were confirmed (69%). As expected, the AMSQ showed moderate to strong relationships with the instruments measuring similar constructs. The test-retest reliability coefficient was 0.96 (95% Confidence Interval 0.94-0.97); SEM was 6.3 (6.3% of scale range); SDC was 17.5 (on a sale from 0 to 100). Different administration methods showed good reliability (ICC 0.88-0.94) and small standard errors (SEM 5.6-7.2). CONCLUSION: The AMSQ shows satisfying results for validity and excellent reliability; allowing for proper use in research. Due to a large SDC value, caution is needed when using the AMSQ in individual patient care. Further research should determine whether the SDC is smaller than the minimal important change. Implications for Rehabilitation The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) measures activity limitations due to hand and arm functioning in patients with Multiple Sclerosis (MS). Results of this study confirm adequate validity and reliability of the AMSQ in patient with MS. The equivalence of scores from online, paper or interview administration is supported. A change score of >=18 points on the scale of the AMSQ (on a scale 0 100) needs to occur to be certain a change beyond measurement error has occurred in an individual patient. PMID- 27665842 TI - Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway. AB - Although all-trans retinoic acid (ATRA) is regarded as a prominent example of differentiation therapy, it is not effective for the treatment of other subtypes of acute myeloid leukemia (AML) beyond acute promyelocytic leukemia (APL). Therefore, new strategies need to be explored to extend the efficacy of ATRA based therapy to non-APL AML patients. In the present study, staurosporine, a protein kinase C (PKC) pan-inhibitor, exhibited synergism with ATRA to promote granulocytic differentiation in poorly ATRA-sensitive U937 cells but not in ATRA unresponsive K562 and Kasumi cells. Staurosporine or the combined treatment did not affect PKC activity in U937 cells. Moreover, other selective PKC inhibitors, UCN-01, Go6976 or rottlerin failed to enhance ATRA-induced granulocytic differentiation in U937 cells. Therefore, staurosporine-enhanced ATRA-induced granulocytic differentiation in U937 cells may be independent of PKC. Staurosporine activated mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK). Meanwhile, staurosporine also enhanced ATRA-promoted upregulation of the protein level of CCAAT/enhancer binding protein beta (C/EBPbeta) and C/EBPepsilon in U937 cells. Furthermore, blockade of MEK activation suppressed staurosporine-enhanced differentiation as well as the elevated protein level of C/EBPs. Taken together, we concluded that staurosporine enhanced ATRA-induced granulocytic differentiation in U937 cells via MEK/ERK-mediated modulation of the protein level of C/EBPs. PMID- 27665843 TI - Low frequency plasmons in thin-wire structures: a commentary. PMID- 27665844 TI - Association of pleural effusion with an early molecular response in patients with newly diagnosed chronic-phase chronic myeloid leukemia receiving dasatinib: Results of a D-First study. AB - Despite the efficacy and safety of dasatinib treatment for chronic-phase chronic myeloid leukemia (CML-CP), adverse effects such as pleural effusion (PE) are still a serious concern. We determined the clinical significance of PE incidence using patient data derived from the D-First clinical study. In the present study, chest radiography and quantification of specific lymphocyte subsets were performed routinely after initiation of dasatinib treatment. Among 52 patients with newly diagnosed CML-CP, 17 (33%) developed PE within 18 months after initial dasatinib administration, but all cases were moderate (Grade 1, 10 patients; Grade 2, 7 patients). CD56+ lymphocyte counts at 1 month correlated significantly with the incidence of PE, whereas lymphocytosis did not. The major molecular response (MMR) rate at 3 months (although not at later times) was significantly higher in PE-positive patients than PE-negative patients (59% versus 24%, respectively; P=0.013). Deep molecular response rates did not differ significantly between the PE groups at any time point during the observation period. Our results suggest that an immune-mediated mechanism involving natural killer cells underlies the development of PE in patients receiving dasatinib for 18 months. This mechanism likely promotes transient tumor regression in patients newly diagnosed with CML-CP. PMID- 27665845 TI - Amides Do Not Always Work: Observation of Guest Binding in an Amide Functionalized Porous Metal-Organic Framework. AB - An amide-functionalized metal organic framework (MOF) material, MFM-136, shows a high CO2 uptake of 12.6 mmol g-1 at 20 bar and 298 K. MFM-136 is the first example of an acylamide pyrimidyl isophthalate MOF without open metal sites and, thus, provides a unique platform to study guest binding, particularly the role of free amides. Neutron diffraction reveals that, surprisingly, there is no direct binding between the adsorbed CO2/CH4 molecules and the pendant amide group in the pore. This observation has been confirmed unambiguously by inelastic neutron spectroscopy. This suggests that introduction of functional groups solely may not necessarily induce specific guest-host binding in porous materials, but it is a combination of pore size, geometry, and functional group that leads to enhanced gas adsorption properties. PMID- 27665846 TI - Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro. AB - AIM: Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms. METHODS: Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process. RESULTS: DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 MUmol/L, respectively, at 24 h of treatment. Treatment with DI (10 100 MUmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase dependent apoptosis in AGS and HGC-27 cells. CONCLUSION: DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy. PMID- 27665849 TI - Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis. AB - AIM: Iloperidone is an atypical antipsychotic drug that is mainly metabolized by CYP2D6, CYP3A4, and cytosolic enzymes. Previous studies show that extensive and poor metabolizers of CYP2D6 exhibit different plasma concentrations of iloperidone and its metabolites. The aim of this study was to develop a parent metabolite population pharmacokinetic (PPK) model to quantify the effects of CYP2D6*10 allele on the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients. METHODS: Seventy Chinese schizophrenia patients were enrolled, from whom limited blood samples were collected on d 15 (0 h) and d 28 (0, 4 and 12 h after drug administration). The plasma concentrations of iloperidone and its metabolites M1 (P-88) and M2 (P-95) were simultaneously detected using a validated HPLC-MS assay. CYP2D6*10 (rs1065852) genotyping was performed. A PPK model was developed based on data from the patients using the NONMEM software (version 7.2). A one-compartment model with first-order absorption and elimination was used to describe the pharmacokinetic data related to iloperidone and its metabolites. RESULTS: Patients with the CYP2D6*10 T/T genotype had significantly higher concentrations of iloperidone and M1, and lower concentrations of M2 than the patients with C/C or C/T genotypes. The CYP2D6*10 genotype affected the elimination constants for transformation of iloperidone to the metabolites M1 (K23) and M2 (K24). The K23 value of the patients with T/T genotype was 1.34-fold as great as that of the patients with C/C or C/T genotype. The K24 value of the patients with C/T and T/T genotypes was 0.693- and 0.492 fold, respectively, as low as that of the patients with C/C genotype. CONCLUSION: CYP2D6*10 mutations affect the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients, suggesting that the clinical doses of iloperidone for patients with CYP2D6*10 mutations need to be optimized. PMID- 27665847 TI - RAD18 polymorphisms are associated with platinum-based chemotherapy toxicity in Chinese patients with non-small cell lung cancer. AB - AIM: Although targeted therapy is very efficient for lung cancer, traditional platinum-based chemotherapies are still the principal strategy in the absence of positive biomarkers. The aim of the present study is to evaluate the contribution of RAD18 polymorphisms to platinum-chemotherapy response and its potential side effects in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 1021 Chinese patients with histological diagnosis of advanced NSCLC were enrolled. Treatment responses were classified into 4 categories (complete response, partial response, stable disease and progressive disease). Gastrointestinal and hematological toxicity incidences were assessed twice a week during the first-line treatment. Ten RAD18 SNPs were genotyped. A logistic regression model was utilized to analyze the associations between RAD18 SNPs and treatment response or toxicity. RESULTS: Among the 10 SNPs tested, none was significantly correlated with the treatment response in a combined cohort. For gastrointestinal toxicity incidences, rs586014 was significantly associated with an increased risk of grade 3 or 4 gastrointestinal toxicity in non-smokers and in the combined cohort; rs654448 and rs618784 were significantly associated with gastrointestinal toxicity in non-smokers; rs6763823 was significantly associated with gastrointestinal toxicity in smokers. For hematological toxicity incidences, rs586014, rs654448 and rs618784 were significantly associated with hematologic toxicity in non-smokers; rs6763823 and rs9880051 were significantly associated with leukocytopenia in smokers. CONCLUSION: RAD18 polymorphisms are correlated with the side effects of platinum-chemotherapy in Chinese patients with advanced NSCLC. PMID- 27665848 TI - Inhibition of tissue transglutaminase promotes Abeta-induced apoptosis in SH-SY5Y cells. AB - AIM: Tissue transglutaminase (tTG) catalyzes proteins, including beta-amyloid (Abeta), to cross-link as a gamma-glutamyl-epsilon-lysine structure isopeptide, which is highly resistant to proteolysis. Thus, tTG plays an important role in protein accumulation in Alzheimer's disease (AD). In the present study, we examined the effect of an irreversible tTG inhibitor, NTU283, on Abeta mimic induced AD pathogenesis in SH-SY5Y cells. METHODS: Western blot and in-cell Western analyses were used to detect tTG and isopeptide (representing the enzyme activity of tTG) protein levels. Moreover, Hoechst and PI co-staining was performed, and caspase-3 and caspase-7 activities and the Bax/Bcl-2 ratio were determined to evaluate the effects of NTU283 on apoptosis. RESULTS: The results confirmed that tTG activity was inhibited by NTU283 20-500 MUmol/L in a concentration-dependent manner in SH-SY5Y cells. Contrary to our expectations, however, the isopeptide bonds were increased when cells were co-treated with Abeta and NTU283. In addition, NTU283 alone did not induce apoptosis in SH-SY5Y cells. However, when co-applied with Abeta, NTU283 promoted rather than inhibited Abeta-induced apoptosis. Consistent with the apoptotic rate, pretreating cells with different concentrations of NTU283 and Abeta significantly increased the activities of caspase-3 and caspase-7 as well as the ratio of Bax/Bcl-2. CONCLUSION: Irreversible inhibition of tTG activity did not block but rather promoted Abeta-induced apoptosis, which indicated that tTG has complex functions in AD pathogenesis. PMID- 27665851 TI - Radial artery ultrasound predicts the success of transradial coronary angiography. AB - BACKGROUND: The transradial approach has become the preferred vascular access during conventional coronary angiography (CCA). Hereby, we evaluated the impact of pre-procedural radial artery diameter (RAD), the cross-sectional area (CSA), and the perimeter on vascular complications (VACs). METHODS: We conducted a single-center prospective analysis of 513 patients who underwent CCA. Radial artery ultrasonography was performed before and after CCA to measure the RAD, CSA, and perimeter. RESULTS: The average RAD, CSA, and perimeter were 2.60 +/- 0.48 mm, 6.2 +/- 3.0 mm2, and 8.9 +/- 1.7 mm, respectively. Vascular complications were reported in 56 (11%) patients. The RAD, CSA, and perimeter were significantly smaller in patients in whom procedure-related VACs were observed than in those with no complications: 2.3 +/- 0.5 vs. 2.70 +/- 0.54 mm (p = 0.0001), 4.9 +/- 2.1 vs. 6.4 +/- 3 mm2 (p = 0.001), and 7.6 +/- 2.1 vs. 9.2 +/- 1.6 mm (p = 0.0001), respectively. Univariate logistic regression showed that RAD, CSA and perimeter can independently predict VACs (OR 0.833, 95% CI 0.777 0.894, p < 0.0001; OR 0.647, 95% CI 0.541-0.773, p < 0.0001; OR 0.545, 95% CI 0.446-0.665, p < 0.0001, respectively). CONCLUSIONS: Ultrasonographic study of the radial artery before CCA can provide valuable information regarding vascular access. PMID- 27665850 TI - Ferulic acid prevents LPS-induced up-regulation of PDE4B and stimulates the cAMP/CREB signaling pathway in PC12 cells. AB - AIM: Phosphodiesterase 4 (PDE4) isozymes are involved in different functions, depending on their patterns of distribution in the brain. The PDE4 subtypes are distributed in different inflammatory cells, and appear to be important regulators of inflammatory processes. In this study we examined the effects of ferulic acid (FA), a plant component with strong anti-oxidant and anti inflammatory activities, on lipopolysaccharide (LPS)-induced up-regulation of phosphodiesterase 4B (PDE4B) in PC12 cells, which in turn regulated cellular cAMP levels and the cAMP/cAMP response element binding protein (CREB) pathway in the cells. METHODS: PC12 cells were treated with LPS (1 MUg/mL) for 8 h, and the changes of F-actin were detected using laser scanning confocal microscopy. The levels of pro-inflammatory cytokines were measured suing ELISA kits, and PDE4B specific enzymatic activity was assessed with a PDE4B assay kit. The mRNA levels of PDE4B were analyzed with Q-PCR, and the protein levels of CREB and phosphorylated CREB (pCREB) were determined using immunoblotting. Furthermore, molecular docking was used to identify the interaction between PDE4B2 and FA. RESULTS: Treatment of PC12 cells with LPS induced thick bundles of actin filaments appearing in the F-actin cytoskeleton, which were ameliorated by pretreatment with FA (10-40 MUmol/L) or with a PDE4B inhibitor rolipram (30 MUmol/L). Pretreatment with FA dose-dependently inhibited the LPS-induced production of TNF-alpha and IL-1beta in PC12 cells. Furthermore, pretreatment with FA dose-dependently attenuated the LPS-induced up-regulation of PDE4 activity in PC12 cells. Moreover, pretreatment with FA decreased LPS-induced up regulation of the PDE4B mRNA, and reversed LPS-induced down-regulation of CREB and pCREB in PC12 cells. The molecular docking results revealed electrostatic and hydrophobic interactions between FA and PDE4B2. CONCLUSION: The beneficial effects of FA in PC12 cells might be conferred through inhibition of LPS-induced up-regulation of PDE4B and stimulation of cAMP/CREB signaling pathway. Therefore, FA may be a potential therapeutic intervention for the treatment of neuroinflammatory diseases such as AD. PMID- 27665852 TI - Five-year outcomes of chronic total occlusion treatment with a biolimus A9 eluting biodegradable polymer stent versus a sirolimus-eluting permanent polymer stent in the LEADERS all-comers trial. AB - BACKGROUND: Few data are available on long-term follow-up of drug-eluting stents in the treatment of chronic total occlusion (CTO). The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9TM eluting stent (BES) with a sirolimus-eluting stent (SES). METHODS: Among 1,707 patients enrolled in the prospective, multi-center, all-comers LEADERS trial, 81 with CTOs were treated with either a BES (n = 45) or a SES (n = 36). The primary endpoint was the occurrence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI) and clinically-indicated target vessel revascularization (TVR). RESULTS: At 5 years, the rate of MACE was numerically higher in the CTO group than in the non-CTO group (29.6% vs. 23.3%; p = 0.173), with a significant increase in the incidence of target lesion revascularization (TLR) (21.0 vs. 12.6; p = 0.033), but no difference in stent thrombosis (ST). Patients with CTO receiving a BES demonstrated a lower incidence of MACE (22.2% vs. 38.9%; p = 0.147) with a significant reduction in TLR compared to patients receiving a SES (11.1% vs. 33.3%, p = 0.0214) with an incidence similar to that observed in the non-CTO group treated with BES (11.6%). Definite ST at 5 years nearly halved in the BES group (4.4% vs. 8.3%, p = 0.478) with no ST in the BES group after the first year (0% vs. 8.3%, p for interaction = 0.009). CONCLUSIONS: The use of a BES showed a reduction in MACE, TVR, TLR, and ST over time in the CTO subset with similar outcome as for non-CTO lesions. PMID- 27665853 TI - Association of factor XIII Val34Leu polymorphism and coronary artery disease: A meta-analysis. AB - BACKGROUND: Factor XIII plays an important role in the stabilization of the linkage between fibrins and in the pathophysiology of coronary artery disease (CAD). The association between factor XIII Val34Leu polymorphism and CAD risk remains controversial. METHODS: We conducted a meta-analysis of 36 studies involving 26,940 cases and 34,694 controls. Subgroup analyses were performed with division of data into disease (myocardial infarction [MI], CAD without MI), age, and sex. RESULTS: Factor XIII Val34Leu polymorphism was significantly associated with ove all CAD risk (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.03-1.06, p = 0.004) and MI risk (OR = 1.15, 95% CI 1.07-1.25, p = 0.0003), but not with CAD without MI risk (OR = 1.00, 95% CI 0.87-1.15, p = 0.96). In the subgroup analysis by age and sex, there was no association between Val34Leu polymorphism and CAD. CONCLUSIONS: This meta-analysis found that factor XIII Val34Leu polymorphism was associated with CAD risk, especially MI, but not with CAD without MI. In addition, age and sex did not affect the relationship between factor XIII Val34Leu polymorphism and CAD risk. PMID- 27665854 TI - Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations. AB - BACKGROUND: The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. METHODS: For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 +/- 1 degrees C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. RESULTS: Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. CONCLUSIONS: We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress. PMID- 27665855 TI - Evaluation of plasma PCSK9 concentrations, transcript of LDL receptor, as well as the total number of monocyte LDL receptors in acute coronary syndrome patients. AB - BACKGROUND: Before our study, there were no data concerning complex evaluation of: plasma PCSK9 concentrations, transcript LDL receptor (LDLR), as well as the total amount of monocytes' LDLR in acute coronary syndrome (ACS) patients. PCSK9 levels in a few cohort studies were found to correlate with the number of white blood cells (WBC) or platelets (PLT). The study aims to evaluate PCSK9-LDLR concentrations, as well as to find any association between PCSK9 and WBC or PLT. METHODS: The study group included 95 consecutive patients with acute myocardial infarction, in whom angiography/angioplasty of the culprit vessel was performed. The control group consisted of 10 healthy young volunteers. Thirty patients from the studied group were qualified for further percutaneous revascularization after 3 months. Laboratory tests were performed using commercially available kits. LDLR expression on monocyte surface was measured by flow cytometry, but the mRNA level for LDLR was established by real time polymerase chain reaction. The PCSK9 plasma concentration was measured by ELISA kits. RESULTS: Higher concentration of PCSK9 and amount of LDLR on monocytes surface were observed in patients with ACS compared with healthy young volunteers (number of LDLRs on monocytes [reaction units] 10.8 +/- 9.6 vs. 41.8 +/- 11.8, p < 0.001, PCSK9 [ng/mL] 295.4 +/- 76.4 vs. 213 +/- 63.2, p < 0.001). A similar relationship was observed after application of 3-month intensive lipid-lowering therapy in patients with ACS (n = 30, PCSK9 [ng/mL] 281.1 +/- 59.5 vs. 358.5 +/- 74.7, p < 0.001, LDLR transcript [reaction units] 0.6 +/- 0.32 vs. 1.87 +/- 0.24, p < 0.001, number of LDLRs on monocytes [reaction units] 5.9 +/- 3.1 vs. 22.3 +/- 3.8, p < 0.001). There were no significant differences in levels of PCSK9, LDLR between patients with ST segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). There was no relation of the PCSK9 with WBC as well as with PLT. CONCLUSIONS: We observed significantly higher concentration of PCSK9, and significantly higher levels of mRNA LDLR transcript in patients with ACS compared with healthy young volunteers. A similar pattern was observed after 3 months of intensive statin therapy among patients with ACS. There were no differences in these parameters between patients with STEMI vs. NSTEMI. The results of the study require confirmation in a larger population of patients. PMID- 27665856 TI - How does the estimated phase of menstrual cycle or menopause influence the prevalence of vasovagal syncope induced by head-up tilt test. AB - BACKGROUND: The purpose of this study was to evaluate the prevalence of syncope induced by head-up tilt test (HUTT) and the type of positive vasovagal response to the orthostatic stress in a relationship to the estimated phase of menstrual cycle (follicular phase, luteal phase) or menopause. METHODS: We observed a cohort of 500 women at age 13-89 years (median of age 37.5), referred to HUTT. Phase of the menstrual cycle was determined on the basis of the usual length of menstrual cycle and the day of the cycle at the time of the study. We assumed that the length of the luteal phase is constant and it is 14 days. RESULTS: In premenopausal patients, the occurrence of the mixed and cardioinhibitory response was significantly more frequent in comparison to postmenopausal women (48.8 vs. 35.1% and 19.7 vs. 12.4%, respectively; p < 0.00001), while the occurrence of the vasodepressive one was significantly less frequent (7.3% vs. 28.6%; p < 0.00001) in that group of patients. Women in follicular phase presented vasodepressive response during HUTT more often than woman in the luteal phase (10.0% vs. 4.1%, p < 0.00001). CONCLUSIONS: Among women referred for HUTT, the prevalence of the vasovagal syndrome did not differ between those that were pre- and post menopausal. Higher incidence of vasodepressive reaction in postmenopausal women was observed. Among the premenopausal women, the vasodepressive type of vasovagal syndrome occurred more often in follicular then in luteal phase. PMID- 27665857 TI - Atrial fibrillation following off-pump versus on-pump coronary artery bypass grafting: Incidence and risk factors. AB - BACKGROUND: Postoperative atrial fibrillation (AF) is a common arrhythmia that occurs after coronary artery bypass grafting (CABG). New surgical techniques, particularly off-pump coronary artery bypass (OPCAB), are thought to be less invasive and results in fewer complications, i.e. AF, but available data are inconsistent. The aim of this study is to present the incidence and risk factors of AF in patients operated on with or without cardiopulmonary bypass. METHODS: We studied 1836 consecutive patients with stable coronary artery disease who were operated on with (CABG) or without (OPCAB) cardiopulmonary bypass. The patients were monitored using a continuous electrocardiogram monitoring system until the sixth postoperative day. RESULTS: Atrial fibrillation occurred in 18.3% and 19.3% of CABG and OPCAB patients, respectively (p = 0.3). The peak incidence of arrhythmia was observed between the second and third postoperative day in both CABG and OPCAB patients (36% and 41%, respectively). Patient's age and history of hypertension were significant predictors of postoperative AF (OR 1.38, 95% CI 1.01-1.76, p = 0.0002; and OR 1.38, 95% CI 1.01-1.76, p = 0.008, respectively). Patients who developed AF vs. without AF had significantly higher rates of complications such as death (3.1% vs. 1.2%, p = 0.01), reoperation (5.2% vs. 2.8%, p = 0.02), and the need to utilize intra-aortic balloon pump (IABP) (6.8% vs. 3.4%, p = 0.002). Use of IABP and reoperation were significant perioperative predictors of the arrhythmia (OR 2.1, 95% CI 1.27-3.4, p = 0.003; and OR 1.9, 95% CI 1.09-3.30, p = 0.02, respectively). AF was also associated with a prolonged stay in an intensive care unit (72.5 +/- 78.8 for patients with AF vs. 34.6 +/- 25.2 for patients with sinus rhythm, p = 0.000001). CONCLUSIONS: In patients undergoing CABG, postoperative AF is a common arrhythmia independent of the type of surgical procedure. PMID- 27665858 TI - Sirolimus-eluting stent is superior to paclitaxel-eluting stent for coronary intervention in patients with renal insufficiency: Long-term clinical outcomes. AB - BACKGROUND: Renal insufficiency (RI) is an independent risk factor for the adverse cardiovascular events. Long-term clinical outcome of percutaneous coronary intervention (PCI) in patients with RI is unknown especially in the era of first generation drug-eluting stents (DES). This study aims at comparing clinical outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) based on large scaled registry. METHODS: Patients who underwent PCI with DES from January 2004 to December 2009 in the Catholic University of Korea PCI (COACT) registry were prospectively enrolled. A group of 1,033 patients with RI, defined as estimated glomerular filtration rate under 60 mL/min, were analyzed. Major adverse cardiac events (MACE), including all-cause death, non fatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR) according to the type of stents were compared. RESULTS: Median follow-up period was 810 days (interquartile range: from 361 to 1,354 days). A group of 612 (59.2%) patients were treated with SES and 421 (40.8%) patients were treated with PES. The PES vs. SES group had significantly higher rate of MACE (35.9% vs. 28.3%, p = 0.01). In multivariate Cox hazard regression analysis, PES vs. SES group had significantly higher rate of MACE (adjusted hazard ratio [AHR] 1.29, 95% confidence interval [CI] 1.02 1.64, p = 0.033), particularly pronounced by all-cause death (AHR 1.34, 95% CI 1.008-1.770; p = 0.044). In further analysis with propensity score matching, overall findings were consistent. CONCLUSIONS: In patients with RI, PCI using PES provides poorer clinical outcomes than SES in terms of MACE and all-cause death. PMID- 27665859 TI - Left ventricular diastolic dysfunction in normotensive postmenopausal women with type 2 diabetes mellitus. AB - BACKGROUND: The prevalence of heart failure among diabetic patients is high, also in those with normal blood pressure and without coronary artery disease, even when electrocardiogram (ECG) is normal. The goal of our study was to assess the prevalence of left ventricular diastolic dysfunction (LVDD) among diabetic women (DW) and its correlation with glycosylated hemoglobin (HbA1c) levels, obesity status, and ECG parameters. METHODS: A group of 456 consecutive normotensive postmenopausal women affected by type 2 diabetes, diagnosed over 5 years, were enrolled. One hundred normotensive non-diabetic postmenopausal women were included as a control group (CG). Rest ECG and trans-thoracic echocardiogram and Doppler were performed. RESULTS: LVDD was present in 103 (23.3%) out of 456 DW, and 8 out of 100 women in CG (8%), p < 0.001. There was no difference in mean age between the two groups: 56 +/- 13 and 55 +/- 3, respectively (p = 0.3). There were 191 (41.9%) DW with body mass index (BMI) > 30 kg/m2. Among those, there were 56 (12.3%) with significant prevalence of LVDD, while there were 49 (10.7%) with BMI < 30 kg/m2, p < 0.005. DW with HbA1c > 7.5% comprised a group of 243 (53.3%) patients. Among those, there were 45 (9.9%) with higher prevalence of LVDD, and 15 (3.3%) with HbA1c < 7.5%, p < 0.01. Out of a group of 147 (32.2%) DW with abnormal ECG , 21 had LVDD (4.6%), p = 0,1, and 84 (18.8%) had LVDD with normal ECG. CONCLUSIONS: Our data prove a high prevalence of LVDD in asymptomatic diabetic postmenopausal women. This finding is closely related with HbA1c levels and obesity status, not with abnormal ECG, which is a unique cardiologic test recommended by current guidelines in all diabetic patients. We conclude that early detection of high level of HbA1c and obesity (30 kg/m2) may identify women with major risk to develop LVDD. Furthermore, a simple ECG, when normal, is not enough to assess a normal LV diastolic function. PMID- 27665861 TI - The Next Generation of Synthetic Biology Chassis: Moving Synthetic Biology from the Laboratory to the Field. AB - Escherichia coli (E. coli) has played a pivotal role in the development of genetics and molecular biology as scientific fields. It is therefore not surprising that synthetic biology (SB) was built upon E. coli and continues to dominate the field. However, scientific capabilities have advanced from simple gene mutations to the insertion of rationally designed, complex synthetic circuits and creation of entirely synthetic genomes. The point is rapidly approaching where E. coli is no longer an adequate host for the increasingly sophisticated genetic designs of SB. It is time to develop the next generation of SB chassis; robust organisms that can provide the advanced physiology novel synthetic circuits will require to move SB from the laboratory into fieldable technologies. This can be accomplished by developing chassis-specific genetic toolkits that are as extensive as those for E. coli. However, the holy grail of SB would be the development of a universal toolkit that can be ported into any chassis. This viewpoint article underscores the need for new bacterial chassis, as well as discusses some of the important considerations in their selection. It also highlights a few examples of robust, tractable bacterial species that can meet the demands of tomorrow's state-of-the-art in SB. Significant advances have been made in the first 15 years since this field has emerged. However, the advances over the next 15 years will occur not in laboratory organisms, but in fieldable species where the potential of SB can be fully realized in game changing technology. PMID- 27665860 TI - Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions. AB - Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5 year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various "novel" pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin - a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta-adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality. PMID- 27665862 TI - Dose- and time-related effects of caffeine on the testis in immature male rats. AB - We previously showed that prepubertal chronic caffeine exposure adversely affected the development of the testes in male rats. Here we investigated dose- and time-related effects of caffeine consumption on the testis throughout sexual maturation in prepubertal rats. A total of 80 male SD rats were randomly divided into four groups: controls and rats fed 20, 60, or 120 mg caffeine/kg/day, respectively, via gavage for 10, 20, 30, or 40 days. Preputial separation was monitored daily before the rats were sacrificed. Terminal blood samples were collected for hormone assay, and testes were grossly evaluated and weighed. One testis was processed for histological analysis, and the other was collected to isolate Leydig cells. Caffeine exposure significantly increased the relative weight of the testis in a dose-related manner after 30 days of exposure, whereas the absolute testis weight tended to decrease at the 120 mg dose of caffeine. The mean diameter of the seminiferous tubules and height of the germinal epithelium significantly decreased in the caffeine-fed groups after 40 days of caffeine exposure, which was accompanied by a reduced BrdU incorporation rate in germ cells. In addition, caffeine intake significantly reduced in vivo and ex vivo testosterone production in a dose-related manner. Our results demonstrate that caffeine exposure during sexual maturation alter the testicular microarchitecture and also slow germ cell proliferation even at the 20 mg dose level. Furthermore, caffeine may act directly on Leydig cells and interfere with testosterone production in a dose-related manner, consequently delaying onset of sexual maturation. PMID- 27665863 TI - Zinc(II) Binding Site to the Amyloid-beta Peptide: Insights from Spectroscopic Studies with a Wide Series of Modified Peptides. AB - The Zn(II) ion has been linked to Alzheimer's disease (AD) due to its ability to modulate the aggregating properties of the amyloid-beta (Abeta) peptide, where Abeta aggregation is a central event in the etiology of the disease. Delineating Zn(II) binding properties to Abeta is thus a prerequisite to better grasp its potential role in AD. Because of (i) the flexibility of the Abeta peptide, (ii) the multiplicity of anchoring sites, and (iii) the silent nature of the Zn(II) ion in most classical spectroscopies, this is a difficult task. To overcome these difficulties, we have investigated the impact of peptide alterations (mutations, N-terminal acetylation) on the Zn(Abeta) X-ray absorption spectroscopy fingerprint and on the Zn(II)-induced modifications of the Abeta peptides' NMR signatures. We propose a tetrahedrally bound Zn(II) ion, in which the coordination sphere is made by two His residues and two carboxylate side chains. Equilibria between equivalent ligands for one Zn(II) binding position have also been observed, the predominant site being made by the side chains of His6, His13 or His14, Glu11, and Asp1 or Glu3 or Asp7, with a slight preference for Asp1. PMID- 27665864 TI - Apolipoprotein E genotyping using PCR-GoldMag lateral flow assay and its clinical applications. AB - A polymerase chain reaction-gold magnetic nanoparticles lateral flow assay (PCR GoldMag LFA) has been developed via integrating multiplex amplification refractory mutation system PCR (multi-ARMS-PCR) with GoldMag-based LFA for the visual detection of single-nucleotide polymorphisms (SNPs). This assay was applied to genotype Apolipoprotein E (ApoE). ApoE genotyping is important due to the predictive value for the development of coronary artery disease and Alzheimer's disease. The method requires two steps: i) Simultaneous amplifications of the two polymorphic codons (ApoE 158 and 112), performed in separated reactions using multi-ARMS-PCR; and ii) detection of the wild-type and mutant PCR products via dual immunoreactions, which can be performed in ~5 min. Within two LFAs, anti-digoxin antibody-conjugated GoldMag probes bind digoxin labeled wild-type PCR products, and anti-fluorescein isothiocyanate (FITC) antibody-conjugated GoldMag probes bind FITC-labeled mutant PCR products. All PCR products are biotin labeled and are detected by streptavidin-coated regions on the LFA strip, resulting in a red color. The current approach is capable of detecting the SNPs of ApoE in ~1.5 h, with a broad detection range from 10-1,000 ng of genomic DNA. Thus, the present protocol may facilitate simple, fast and cost-effective screening for important SNPs, as demonstrated by the evaluation of the prevalence of ApoE variants in a Han Chinese cohort. PMID- 27665866 TI - Robotic Assessment of Upper Limb Function after Proximal Humeral Fracture: Personal Experience as A Patient and Occupational Therapist. AB - Robotics is an emerging field in rehabilitation medicine. Robots have the potential to complement traditional clinical assessments because they can measure functions more precisely and quantitatively than current clinical assessments. We present a patient with a proximal humeral fracture whose recovery process was evaluated with an exoskeleton robotic device. The patient, a 34-year-old woman, suffered a left proximal humeral fracture while snowboarding. She is an occupational therapist and is the first author of this study. With conservative therapy, fracture union was seen on X-ray at 6 weeks post-injury. At that time, the patient was permitted to move her left upper limb actively within the tolerance of pain. We assessed the function of the injured upper limb at 6, 7, and 12 weeks post-injury with the KINARM exoskeleton robotic device and with conventional clinical measures. The active range of motion and the muscle strength of the left shoulder improved over time. Using robotic assessment, the precise movement profiles, position sense, and functional ability of both arms were quantified and also showed progressive improvement over time. Assessment with a robotic device of the recovery process after proximal humeral fracture allowed quantification of functional impairments that could not be felt subjectively nor identified with conventional clinical assessments. PMID- 27665865 TI - Mutation analysis by direct and whole exome sequencing in familial and sporadic tooth agenesis. AB - Dental agenesis is one of the most common congenital craniofacial abnormalities. Dental agenesis can be classified, relative to the number of missing teeth (excluding third molars), as hypodontia (1 to 5 missing teeth), oligodontia (6 or more missing teeth), or anodontia (lack of all teeth). Tooth agenesis may occur either in association with genetic syndromes, based on the presence of other inherited abnormalities, or as a non-syndromic trait, with both familiar and sporadic cases reported. In this study, we enrolled 16 individuals affected by tooth agenesis, prevalently hypodontia, and we carried out direct Sanger sequencing of paired box 9 (PAX9) and Msh homeobox 1 (MSX1) genes in 9 subjects. Since no mutations were identified, we performed whole exome sequencing (WES) in the members of 5 families to identify causative gene mutations either novel or previously described. Three individuals carried a known homozygous disease mutation in the Wnt family member 10A (WNT10A) gene (rs121908120). Interestingly, two of these individuals were siblings and also carried a heterozygous functional variant in EDAR-associated death domain (EDARADD) (rs114632254), another disease causing gene, generating a combination of genetic variants never described until now. The analysis of exome sequencing data in the members of other 3 families highlighted new candidate genes potentially involved in tooth agenesis and considered suitable for future studies. Overall, our study confirmed the major role played by WNT10A in tooth agenesis and the genetic heterogeneity of this disease. Moreover, as more genes are shown to be involved in tooth agenesis, WES analysis may be an effective approach to search for genetic variants in familiar or sporadic tooth agenesis, at least in more severe clinical manifestations. PMID- 27665867 TI - An insertion/deletion polymorphism within the 3'-untranslated region of COL1A2 confers susceptibility to osteoporosis. AB - Polymorphisms located in microRNA (miRNA) binding sites may interfere with the interaction between miRNAs and mRNAs, and thereby alter the expression of genes. The current study aimed to investigate the association between an insertion/deletion (INS/DEL) polymorphism in the 3'-untranslated region (3'-UTR) of COL1A2 and the risk of developing osteoporosis. In the present study, COL1A2 was identified as a target gene of let-7g in osteoblast cells obtained from patients, using a luciferase reporter system. This was further confirmed by the observation that exogenous overexpression of let-7g in the osteoblast cells downregulated the expression of COL1A2 in the cells in the INS/INS group, however not in the DEL/DEL group. In addition, a total of 487 subjects were enrolled in the present study and their bone mineral density (BMD) was measured. The BMD at the four tested sites, the femoral neck, total left hip, L1-L4 and intertrochanteric areas, were significantly reduced in the INS/DEL or DEL/DEL group compared with the INS/INS group. Furthermore, the levels of COL1A2 and let 7g were measured in the primary osteoblasts obtained from 48 patients with osteoporosis. While the let-7g levels were comparable between each genotype group, the expression level of COL1A2 in the DEL/DEL and INS/DEL group was significantly greater compared with the INS/INS group. In conclusion, the present study demonstrated that the INS/DEL polymorphism in the 3'-UTR of COL1A2 is able to interfere with the interaction between miRNA and mRNA. In addition, it is the first study, to the best of our knowledge, to indicate that the minor allele (Del) is associated with a reduced risk of developing osteoporosis. PMID- 27665869 TI - Green light for nurse prescribing. AB - The Royal College of Nursing has said there must be no further delays in the implementation of nurse prescribing after a government go-ahead for pilot projects across the country. PMID- 27665870 TI - Large scale changes underway in welfare state shake-up. AB - A radical shake-up of the welfare state, with changes likely in many areas including benefit payments for the long-term sick, seems almost certain following yesterday's Budget. PMID- 27665868 TI - Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/beta-catenin signaling in human osteosarcoma cells. AB - Although multiple chemotherapeutic agents have been used for osteosarcoma (OS) treatment, their mechanisms need further study. Ursolic acid (UA), a pentacyclic triterpenoid, can reduce cell proliferation and induce apoptosis in various cancer cells, such as OS. However, the exact mechanism underlying this function remains unclear. In this study, we investigated the anti-proliferative effect of UA in human OS 143B cells and dissected the possible molecular mechanism underlying this effect. We demonstrated that UA can reduce cell proliferation, induce apoptosis and arrest cell cycle in 143B cells, as well as inhibit OS tumor growth in a mouse xenograft model. Using a luciferase reporter assay, we found that the Wnt/beta-catenin signaling is inhibited by UA in 143B cells. Correspondingly, the expression level and nuclear translocation of beta-catenin are both decreased by UA. Exogenous expression of beta-catenin attenuates the anticancer effect of UA in 143B cells, while knockdown of beta-catenin enhances this effect. UA increases the expression level of p53 in a concentration dependent manner, and inhibition of p53 reduces the anticancer effect of UA in 143B cells. Moreover, inhibition of p53 partly reverses the UA-induced downregulation of beta-catenin, as do the targets of Wnt/beta-catenin signaling, such as c-Myc and cyclin D1. Our findings indicated that UA can inhibit the proliferation of 143B OS cells through inactivation of Wnt/beta-catenin signaling, which may be mediated partly by upregulating the expression of p53. PMID- 27665871 TI - ? AB - A three-day candlelit vigil was held in St James' Church in Piccadilly as part of a campaign to halt the threatened closure of London's Royal Marsden Hospital. Campaigners, led by actress Fiona Fullerton, also delivered a massive petition bearing 900,000 signatures to Downing Street in protest at the closure plans. Yona Zalosor (second from left), a former patient at the hospital. Ls shown with three members of the Marsden Patients Action Group. From left: Melissa Bennett. Philip Wood and Jenny Bennett. PMID- 27665872 TI - Welsh bureaucrats gain as nursing numbers plummet. AB - Nursing numbers in Wales have been cur while the number of bureaucrats has more than quadrupled, new figures have confirmed. PMID- 27665873 TI - 380 posts in York are under threat. AB - Hundreds of jobs are to go at York Health Services NHS Trust over the next two and a half years to make up a L1.5 million deficit, says the RCN. PMID- 27665875 TI - Mixed reaction to BMA survey criticisms. AB - Shock figures from the British Medical Association (BMA) claiming that community care is a failure have been greeted with caution by the RCN. PMID- 27665874 TI - P2000 courses in London to go ahead. AB - Funding for Project 2000 courses in London has been confirmed following uncertainty over nurse education caused by the Tomlinson report. PMID- 27665877 TI - ? AB - Nurses Against Smoking, a new campaign group run by the RCN's Respiratory Nurses' Forum, sent a delegation to Downing Street last week to demand a steep rise in tobacco tax to discourage smokers. Shown outside Number 10 are (left to right): Adrienne Brewin, Chris Robbins, Lynne Stanley, Raymond Duffy and Anne Crawford. PMID- 27665876 TI - Urgent inquiry into Scottish staff injuries. AB - Hospitals and trusts in Scotland have been instructed to launch immediate investigations into the incidence of sharps and back injuries among staff, with targets set to reduce such accidents 'without delay'. PMID- 27665878 TI - DoH bows to pressure on children's care. AB - Large increases in the number of paediatric intensive care nurses are being promised by the government after a scathing report showed that critically ill children were being turned away from hospitals because of a lack of proper facilities. PMID- 27665879 TI - Research base is the key, says Hancock. AB - Securing an adequate research base for nursing is fundamental to securing the profession's future, RCN General Secretary Christine Hancock has told researchers in Edinburgh. PMID- 27665881 TI - Doctors 'are bullying junior nurses'. AB - Nurses are being bullied by doctors because they no longer have seniors to protect them, RCN Scottish Secretary June Andrews said last week. PMID- 27665880 TI - Midland 'shambles'. AB - Investigations into how West Midlands Health Authority wasted at least L10 million of public money have been welcomed by the government. PMID- 27665883 TI - RCN's Northern Ireland health initiative is runaway success. AB - A campaign highlighting health service problems in Northern Ireland has been hailed as a success less than a month after it started. PMID- 27665885 TI - HVA launches campaign against trust job cuts proposals. AB - The Health Visitors' Association is launching a campaign against plans by Harrow Community Health Services Trust, which could mean up to 15 health visitor redundancies. PMID- 27665884 TI - RCN reassurance on standards. AB - The RCN has sought to reassure parents and children of the high quality of patient care at Liverpool's Alder Hey Children's Hospital after a turbulent period during which management was blamed for falling standards. PMID- 27665886 TI - ? AB - A new exhibition focusing on health from the artist's perspective opened at the Wellcome Foundation in London last week. Ron Sutton, of Wellcome's Community Affairs department, is shown with nurse Mary Neiland, (left) Clinical Service Manager for the Charing Cross and Chelsea and Westminster Hospitals and Anne Gibson, manager of St Christopher's Hospice Day Care Centre, who were among the first to view some of the paintings on show. PMID- 27665887 TI - Nurses 'reluctant' to promote themselves. AB - Nursing experience should be used to promote the profession so people realise nurses have a vital role to play in a quality NHS, a conference on marketing and nursing heard. PMID- 27665888 TI - 'Low level' of NHS efficiency. AB - Vital NHS resources are being diverted to 'unproven and perhaps inefficient' activities in a misguided bid to make the health service more effective, say researchers at the Centre for Health Economics. PMID- 27665889 TI - ? AB - The RCN recently awarded degrees to graduates of its Institute of Advanced Nursing Education. Alison Allen, with daughter Phillipa, received a BSc in Nursing Studies. Richard Hogston and Elaine Mairis received the first Masters degrees to be awarded by the IANE. PMID- 27665890 TI - SHSA nurses should not fear trust status. AB - Nurses working in forensic mental health have nothing to fear as a result of their hospitals becoming trusts, a conference on sharing good practice was told last week. PMID- 27665892 TI - Bed sharing may increase danger of cot death. AB - Urging mothers to avoid bed sharing with infants could significantly reduce the danger of cot death, new research suggests. PMID- 27665891 TI - Back injury three times more likely for nurses. AB - Nurses are three times more likely to suffer back injuries at work than other occupations, according to a new report. PMID- 27665894 TI - New study aims to solve nuclear illness puzzle. AB - Scientists hope a new study will show conclusively whether the children of nuclear workers are at increased risk of radiation- induced illnesses and conditions. PMID- 27665895 TI - Ecstasy drug could cause lasting damage to brain. AB - Ecstasy, the most popular 'rave drug' in Britain, could cause lasting damage to the : brain, New Scientist reports. PMID- 27665896 TI - Light exercise and life quality after MI. AB - The effect of light exercise on quality of life after myocardial infarction are similar to those obtained from high intensity exercise training. PMID- 27665898 TI - Methadone useful in morphine resistant pain. AB - Switching to methadone may be useful in patients with nocioceptive pain uncontrolled by oral morphine. PMID- 27665897 TI - Commode provision needs rethinking. AB - Health professionals should be aware of people's need for privacy when they provide commodes. PMID- 27665899 TI - Simple solution to stop arthritis damage. AB - Drugs based on common substances such as sugars and carbohydrates may stop the damage caused by rheumatoid arthritis, Australian researchers believe. PMID- 27665900 TI - HRT and breast cancer recurrence link queried. AB - New research strongly suggests that taking hormone replacement therapy does not cause recurrence of breast cancer, as had been feared. PMID- 27665901 TI - Sunday morning on the Chain gang. AB - Every Sunday morning people leave the warmth of their duvets and the colour supplements, and head for one of three London community centres. For some it is an Sam start, for others a rather more leisurely mid-morning. PMID- 27665902 TI - View from the bridge. AB - Daniel Allen joined the mass rally in London against the government's policies and listened to the concerns of nurses from throughout the UK. When 20,000 health care workers and their supporters marched through London recently in protest against the government's health policies, it took them 40 minutes to cross Blackfriars Bridge. Marching five abreast the crowd stretched back a mile. PMID- 27665904 TI - A cry for help. AB - Alison Carter* is one of hundreds of student nurses who have dropped out of Project 2000 courses. But Alison's is no ordinary case because when she resigned, about half-way through the common foundation programme, she was suffering from schizophrenia. PMID- 27665903 TI - Patients still getting little satisfaction. AB - The changes in the health service have not reduced patients' dissatisfaction over hospital, GP or clinic waiting times, or arranging appointments within a reasonable time. Nor have they improved the amount of relevant information given to patients or made them feel they receive greater individual respect from staff. PMID- 27665905 TI - I sold my soul for a rotten hole. AB - We read the report about nursing students paying exorbitant rents for hospital accommodation (Anger over 'totally unacceptable' rent levels, News, November 17). PMID- 27665906 TI - ? AB - I am the mother of a Project 2000 student at Broomsfield Hospital in Chelmsford, a sister hospital to Southend. My daughter and her fellow students pay L130 a month for their substandard accommodation. PMID- 27665907 TI - ? AB - The P2000 students at Southend who complained about their rent levels should be satisfied with the amount they have to pay. PMID- 27665908 TI - Stub out drug tutors' joint initiatives. AB - When I decided to take an RMN diploma, I intended to work with those addicted to drugs. I thought these would be the client group, not my colleagues. PMID- 27665909 TI - Back home we'll be thinking about you. AB - Trudy Rawlins, who trumpeted the value of day care nursing (Express nurse hits out at slowcoaches, Letters, November 10), said that day surgery patients do not have nursing back-up at home. May I remind her of the district nursing sister and the community nursing team's existence. PMID- 27665911 TI - Information exchange. AB - * As a group of nurses representing home care, inpatient and day hospice care in Jersey, we are currently re-evaluating our documentation. We would like to hear from nurses working in palliative care who use care plans common to the above three areas to achieve continuity of care.Gill Osmont Day Hospice Sister Jersey Hospice Care Clarkson House Rue de Haie du Puits Grouvilie Jersey JE3 9DL. PMID- 27665910 TI - Stiff upper lip? You can stoic it. AB - When will 'stoics' such as Graeme Morrison learn that it is precisely attitudes like theirs that perpetuate all that is lamentable in the NHS (If you can't stand the heat, leave the Legion, Letters, November 10). PMID- 27665912 TI - We blush: Queen's support fully shown. AB - I was delighted to see the news report on the Queen's Nursing Institute s Annual Awards for Innovation and Long Service (November 17). PMID- 27665914 TI - Gone loco. AB - As a regular BR customer, I continually wonder why the Duke of Edinburgh Awards Scheme steadfastly refuses to award enamel badges to commuters who successfully get to work by lunchtime on most days. PMID- 27665913 TI - Correction. AB - The clinical news item (Pre-admission plan to save patients' time, November 17) stated the initiative was being conducted at St Thomas' hospital in London. PMID- 27665915 TI - Personnel practice for health service managers: individual development manual Personnel practice for health service managers: individual development manual R Jones M Layte TRACE Ltd 338pp L75.00 0-948132-50-7. AB - From the Shrewsbury Acute Unit, Shropshire HA, under project managers Ron Jones and Maureen Layte comes Personnel Practice for Health Service Managers: Individual Development Manual, an open learning, self-development pack. PMID- 27665916 TI - Career changes for nurses: work opportunities outside hospital Career changes for nurses: work opportunities outside hospital J Lyall Hawker 128pp L5.99 1-874790 03-5. AB - Joanna Lyall's Career Changes for Nurses: Work Opportunities outside Hospital will appeal to all nurses considering a career change (which gives it a huge potential market). PMID- 27665917 TI - A history of mental health nursing A history of mental health nursing P Nolan Chapman & Hali 178pp L11.95 0-412-39820-6 [Formula: see text]. AB - As seen through the eyes of Peter Nolan, A History of Mental Health Nursing is easy to read. The down-to-earth presentation and writing style add to the quality. PMID- 27665918 TI - Sister Suzuki derides again. AB - Hi there, health care workers. Did I tell you about the project I am planning as part of my management course? I would not be exaggerating if I said it is going to be the most exciting innovation yet on my new nursing unit. And it really is a new idea - there is no American influence involved. PMID- 27665919 TI - Your common questions answered. AB - What is the difference between hardware and software? Hardware is the equipment that you buy. If you buy a computer, a monitor screen and a keyboard, this is all hardware. Software refers to the programs that you run on your computer. Thus a wordprocessing package or a spreadsheet program is software. You should note the spelling of program. It has become the convention to spell it the American way. PMID- 27665920 TI - Precisely my type of book. AB - As you may have realised, there are not that many bargains in the personal computer world. But this definitely is one. Designing Business Documents is a comprehensive guide to all aspects of designing documents with a PC. Forget the 'business' in the title - it is likely to be useful to all computer users. PMID- 27665921 TI - Exposure to Sound Vibrations Lead to Transcriptomic, Proteomic and Hormonal Changes in Arabidopsis. AB - Sound vibration (SV) is considered as an external mechanical force that modulates plant growth and development like other mechanical stimuli (e.g., wind, rain, touch and vibration). A number of previous and recent studies reported developmental responses in plants tailored against SV of varied frequencies. This strongly suggests the existence of sophisticated molecular mechanisms for SV perception and signal transduction. Despite this there exists a huge gap in our understanding regarding the SV-mediated molecular alterations, which is a prerequisite to gain insight into SV-mediated plant development. Herein, we investigated the global gene expression changes in Arabidopsis thaliana upon treatment with five different single frequencies of SV at constant amplitude for 1 h. As a next step, we also studied the SV-mediated proteomic changes in Arabidopsis. Data suggested that like other stimuli, SV also activated signature cellular events, for example, scavenging of reactive oxygen species (ROS), alteration of primary metabolism, and hormonal signaling. Phytohormonal analysis indicated that SV-mediated responses were, in part, modulated by specific alterations in phytohormone levels; especially salicylic acid (SA). Notably, several touch regulated genes were also up-regulated by SV treatment suggesting a possible molecular crosstalk among the two mechanical stimuli, sound and touch. Overall, these results provide a molecular basis to SV triggered global transcriptomic, proteomic and hormonal changes in plant. PMID- 27665922 TI - Theoretical Comparison of Optical Properties of Near-Infrared Colloidal Plasmonic Nanoparticles. AB - We study optical properties of near-infrared absorbing colloidal plasmonic nanostructures that are of interest for biomedical theranostic applications: SiO2@Au core-shell particles, Au nanocages and Au nanorods. Full-wave field analysis is used to compare the absorption spectra and field enhancement of these structures as a function of their dimensions and orientation with respect to the incident field polarization. Absorption cross-sections of structures with the same volume and LSPR wavelength are compared to quantify differential performance for imaging, sensing and photothermal applications. The analysis shows that while the LSPR of each structure can be tuned to the NIR, particles with a high degree of rotational symmetry, i.e. the SiO2@Au and nanocage particles, provide superior performance for photothermal applications because their absorption is less sensitive to their orientation, which is random in colloidal applications. The analysis also demonstrates that Au nanocages are advantaged with respect to other structures for imaging, sensing and drug delivery applications as they support abundant E field hot spots along their surface and within their open interior. The modeling approach presented here broadly applies to dilute colloidal plasmonic nanomaterials of arbitrary shapes, sizes and material constituents and is well suited for the rational design of novel plasmon-assisted theranostic applications. PMID- 27665926 TI - Stones: TNFRs mediate CaOx deposition in hyperoxaluria. PMID- 27665925 TI - Structure-function insights reveal the human ribosome as a cancer target for antibiotics. AB - Many antibiotics in clinical use target the bacterial ribosome by interfering with the protein synthesis machinery. However, targeting the human ribosome in the case of protein synthesis deregulations such as in highly proliferating cancer cells has not been investigated at the molecular level up to now. Here we report the structure of the human 80S ribosome with a eukaryote-specific antibiotic and show its anti-proliferative effect on several cancer cell lines. The structure provides insights into the detailed interactions in a ligand binding pocket of the human ribosome that are required for structure-assisted drug design. Furthermore, anti-proliferative dose response in leukaemic cells and interference with synthesis of c-myc and mcl-1 short-lived protein markers reveals specificity of a series of eukaryote-specific antibiotics towards cytosolic rather than mitochondrial ribosomes, uncovering the human ribosome as a promising cancer target. PMID- 27665927 TI - Chronic kidney disease: Gli1+ adventitial cells have a critical role in vascular calcification in CKD. PMID- 27665924 TI - Neuroprotective effect of epidermal growth factor plus growth hormone-releasing peptide-6 resembles hypothermia in experimental stroke. AB - BACKGROUND: Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. OBJECTIVES: The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke. METHODS: (a) Global ischemia was induced in Mongolian gerbils by a 15-min occlusion of both carotid arteries, followed by reperfusion. (b) Focal brain ischemia was achieved by intracerebral injection of endothelin 1 in Wistar rats. In each experiment, three ischemic treatment groups - vehicle, EGF + GHRP 6, and hypothermia - were compared to each other and to a sham-operated control group. End points were survival, neurological scores, and infarct volume. RESULTS: (a) In global ischemia, neurological score at 48-72 h, infarct volume, and neuronal density of hippocampal CA1 zone in gerbils treated with EGF + GHRP-6 were similar to the hypothermia-treated group. (b) In focal ischemia, the neurologic score and infarct volume of rats receiving EGF + GHRP-6 were also similar to animals in the hypothermia group. DISCUSSION: With hypothermia being a good standard neuroprotectant reference, these results provide additional proof of principle for EGF and GHRP-6 co-administration as a potentially neuroprotective stroke therapy. PMID- 27665923 TI - Coffee and cancer risk: A meta-analysis of prospective observational studies. AB - Meta-analyses on coffee and cancer incidence mainly restricted to limited cancers. We carried out a more comprehensive meta-analysis of cohort studies to explore association between coffee and most cancer types. We conducted comprehensive search and summarized relative risk (RR) and 95% confidence intervals for the highest versus lowest coffee intake and cancer using STATA12. We conducted dose-analysis if result suggested significant association. The publication bias was evaluated with begg's and egger's test. Finally, 105 individual prospective studies were included. Inverse associations were observed on oral, pharyngeal, colon, liver, prostate, endometrial cancer and melanoma, with RR 0.69 (95% CI = 0.48-0.99, I2 = 73.4%, P = 0.044), 0.87 (95% CI = 0.78 0.96, I2 = 28.4%, P = 0.007), 0.46 (95% CI = 0.37-0.57, I2 = 0%, P = 0), 0.89 (95% CI = 0.84-0.93, I2 = 30.3%, P = 0.003), 0.73 (95% CI = 0.67-0.80, I2 = 0%, P = 0) and 0.89 (95% CI = 0.80-0.99, I2 = 0%, P = 0.031) respectively. However, the relative risk for lung cancer is 2.18 (95% CI = 1.26-3.75, I2 = 63.3%, P = 0.005). The summary relative risk for increment of 2 cups of coffee were RR = 0.73, 95% CI = 0.67-0.79 for liver cancer, RR = 0.97, 95% CI = 0.96-0.98 for prostate cancer and RR = 0.88, 95% CI = 0.85-0.92 for endometrial cancer. Accordingly, coffee intake was associated with reduced risk of oral, pharynx, liver, colon, prostate, endometrial cancer and melanoma and increased lung cancer risk. PMID- 27665928 TI - Glomerular disease: Crescents in IgAN. PMID- 27665929 TI - Fabry disease: A pharmacological chaperone on the horizon. PMID- 27665930 TI - Identification of Nanocrystalline Inclusions in Bismuth-Doped Silica Fibers and Preforms. AB - The nature of nanocrystalline inclusions and dopant distribution in bismuth-doped silicate fibers and preforms are studied by scanning and transmission electron microscopy, and energy and wavelength-dispersive X-ray microanalysis. The core compositions are Bi:SiO2, Bi:Al2O3-SiO2, Bi:GeO2-SiO2, Bi:Al2O3-GeO2-SiO2, and Bi:P2O5-Al2O3-GeO2-SiO2. Nanocrystals of metallic Bi, Bi2O3, SiO2, GeO2, and Bi4(GeO4)3 are observed in these glasses. These inclusions can be the reason for the background optical loss in bismuth-doped optical fibers. The bismuth concentration of 0.0048+/-0.0006 at% is directly measured in aluminosilicate optical fibers with effective laser generation (slope efficiency of 27% at room temperature). PMID- 27665931 TI - Universite du troisieme age : les besoins en formation continue des personnes agees francophones au Nouveau-Brunswick. AB - Continuing education is the ideal mechanism to allow retired people to maintain their autonomy and health for as long as possible. Despite the importance of education in the development of human beings, very few studies have been identified on the need for continued education in older adults. This quantitative descriptive study allowed us to better understand the interests and the needs of seniors related to continuing education in French-speaking older adults in New Brunswick (n = 408), and to identify the perceptions of participants with regard to the benefits, the challenges and the preferences of seniors for continuing education. Study results indicate that the main interests of participants were for training in technology (computers), gardening and health matters. Given the lack of research in this domain, these results will be useful for future planning of continuing education initiatives for seniors. PMID- 27665932 TI - Drawing them in: professional perspectives on the complexities of engaging 'culturally diverse' young people with sexual and reproductive health promotion and care in Sydney, Australia. AB - Young people from minority ethnic, migrant and refugee backgrounds are widely recognised as being under-served by mainstream sexual and reproductive healthcare in developed economy nations. This paper documents the views of professionals in Australia on the complexities of, and best practice approaches to, engaging members of this group with sexual and reproductive health promotion and care. Semi-structured interviews were conducted with 23 purposively selected key informants (health service providers, policymakers, academics and community advocates). Interviews were transcribed verbatim and coded in NVivo10 using interpretive thematic analysis. Principles of 'cultural competence' were employed to structure the interpretation of findings. Five key themes reveal pivotal aspects of how professionals work in, and make sense of, this complex field. These may be summarised as: (1) appreciating the complexities of cultural diversity; (2) recognising structural barriers and disincentives to engagement; (3) normalising sexual health; (4) balancing 'youth-friendly' and 'culturally competent' priorities; and (5) going beyond simple translation. As migration to Australia continues to diversify the population, an integrated, national approach to the design and delivery of sexual and reproductive health promotion and care would be of value, along with training and support for those involved. Implications may have resonance for other countries similarly engaged in facilitating the successful settlement of migrants and refugees. PMID- 27665933 TI - Being visible: PhotoVoice as assessment for children in a school-based psychiatric setting. AB - BACKGROUND: Recovery-oriented mental health services empower all clients, including youth and their families, to be actively involved in directing their own care. In order to develop person-driven interventions, clinicians must understand what matters from their perspective. Thus, recovery-oriented assessments need self-report measures that adequately capture the domains and content that matter to a range of particular persons. AIM: This study examined if and how PhotoVoice, a participatory research method used to empower and highlight the unique experiences of vulnerable groups, could be used as a recovery-oriented self-report measure for children with a mental health disorder. METHODS: We used PhotoVoice to engage four children with mental health related disorders at a day hospital program for severe behavioural disorders. The children, as co researchers in this participatory approach, created life books from photographs and images of what mattered to them across nine sessions. To examine the PhotoVoice process, we used ethnographic methods, including child interviews and participant observations in their classes and at recess before, during and after the weekly sessions. Our overarching narrative-phenomenological theoretical framework focused data collection and analysis on what mattered most to the children. RESULTS: The PhotoVoice method engaged and empowered the children in articulating what mattered in their everyday lives from their perspective that resulted in a novel, child-generated domain of 'mattering to others' for future self-report measures, and facilitated changes that generalized outside of the group. We illustrate these results by drawing a particularly illustrative case example from the study. CONCLUSION: The PhotoVoice method foregrounded children's perspectives on what matters more explicitly than clinical or parent perspective on function. SIGNIFICANCE: The participatory philosophy and methods of PhotoVoice provides a viable approach to recovery-oriented self-report measures as well as an occupation-based assessment and intervention. PMID- 27665934 TI - MicroRNA-122 as a predictor of HBsAg seroclearance in hepatitis B and C dual infected patients treated with interferon and ribavirin. AB - It has been demonstrated that microRNA-122 (miR-122) plays key roles in the modulation of hepatitis B virus (HBV) replication. This study examined the role of miR-122 in patients with hepatitis C virus (HCV)-HBV dual infection with active hepatitis C who received pegylated interferon-alpha and ribavirin dual therapy. We enrolled 121 patients with HCV-HBV dual infection after dual therapy. Stored serum was collected before treatment. RT-PCR was used to analyze miR-122. HBsAg seroclearance was noted in 37 (30.1%) cases during a median follow-up period of 5.4 years. miR-122 was significantly lower in HBsAg seroclearance patients than in non-HBsAg seroclearance patients (P < 0.014). Multivariate analysis showed that miR-122 was an independent factor of HBsAg seroclearance (OR: 0.30, 95% CI: 0.09-0.98, P = 0.046). miR-122 was significantly higher in patients who were qHBsAg > 100 IU/mL versus <=100 IU/mL (P < 0.001). We concluded that in patients with HBV-HCV dual infection with active hepatitis C, miR-122 was associated with HBsAg seroclearance after therapy and qHBsAg level before therapy, indicating that miR-122 plays key roles in modulating HBV replication. PMID- 27665935 TI - CRHunter: integrating multifaceted information to predict catalytic residues in enzymes. AB - A variety of algorithms have been developed for catalytic residue prediction based on either feature- or template-based methodology. However, no studies have systematically compared these two strategies and further considered whether their combination could improve the prediction performance. Herein, we developed an integrative algorithm named CRHunter by simultaneously using the complementarity between feature- and template-based methodologies and that between structural and sequence information. Several novel structural features were generated by the Delaunay triangulation and Laplacian transformation of enzyme structures. Combining these features with traditional descriptors, we invented two support vector machine feature predictors based on both structural and sequence information. Furthermore, we established two template predictors using structure and profile alignments. Evaluated on datasets with different levels of homology, our feature predictors achieve relatively stable performance, whereas our template predictors yield poor results when the homological relationships become weak. Nevertheless, the hybrid algorithm CRHunter consistently achieves optimal performance among all our predictors. We also illustrate that our methodology can be applied to the predicted structures of enzymes. Compared with state-of-the-art methods, CRHunter yields comparable or better performance on various datasets. Finally, the application of this algorithm to structural genomics targets sheds light on solved protein structures with unknown functions. PMID- 27665937 TI - Measuring Method for Lightning Channel Temperature. AB - In this paper, we demonstrate the temperature of lightning channel utilizing the theory of lightning spectra and the model of local thermodynamic equilibrium (LTE). The impulse current generator platform (ICGS) was used to simulate the lightning discharge channel, and the spectral energy of infrared spectroscopy (930 nm) and the visible spectroscopy (648.2 nm) of the simulated lightning has been calculated. Results indicate that the peaks of luminous intensity of both infrared and visible spectra increase with the lightning current intensity in range of 5-50 kA. Based on the results, the temperature of the lightning channel is derived to be 6140.8-10424 K. Moreover, the temperature of the channel is approximately exponential to the lightning current intensity, which shows good agreement with that of the natural lightning cases. PMID- 27665936 TI - TDP-43 aggregation mirrors TDP-43 knockdown, affecting the expression levels of a common set of proteins. AB - TDP-43 protein plays an important role in regulating transcriptional repression, RNA metabolism, and splicing. Typically it shuttles between the nucleus and the cytoplasm to perform its functions, while abnormal cytoplasmic aggregation of TDP 43 has been associated with neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). For the purpose of this study we selected a set of proteins that were misregulated following silencing of TDP-43 and analysed their expression in a TDP-43-aggregation model cell line HEK293 Flp-in Flag-TDP-43-12x-Q/N F4L. Following TDP-43 sequestration in insoluble aggregates, we observed higher nuclear levels of EIF4A3, and POLDIP3beta, whereas nuclear levels of DNMT3A, HNRNPA3, PABPC1 and POLDIP3alpha dropped, and cytoplasmic levels of RANBP1 dropped. In addition, immunofluorescence signal intensity quantifications showed increased nuclear expression of HNRNPL and YARS, and downregulation of cytoplasmic DPCD. Furthermore, cytoplasmic levels of predominantly nuclear protein ALYREF increased. In conclusion, by identifying a common set of proteins that are differentially expressed in a similar manner in these two different conditions, we show that TDP-43 aggregation has a comparable effect to TDP-43 knockdown. PMID- 27665938 TI - Center-based patient care enhances survival of elderly patients suffering from peripheral arterial disease. AB - OBJECTIVES: Recent advances in catheter-based intervention in patients with symptomatic peripheral arterial disease (PAD) have halved mortality. Mortality of PAD patients still remains high compared to other clinical forms of atherosclerosis. Intensified patient care might increase adherence to medical management and benefit the survival of PAD patients. METHODS: Two patient cohorts were compared in a longitudinal prospective follow-up study. 370 PAD patients were included in the intensified center-based vascular medicine group (VMC group) and 332 PAD patients were treated by their usual primary care physician (PCP group). Survival in both groups was compared by Kaplan-Meier and Cox-regression analyses after 5 years. RESULTS: Survival of patients in the VMC group was 90.8% compared to 66% in the PCP group. Thus, survival was improved by 24.9% by center based care (absolute risk CI: 19-30.7%; 38% relative risk). PCP treatment increased all-cause mortality by a hazard ratio of 3.7 (95% CI: 2.5-5.5; p < .001). Mortality in the VMC group was significantly associated with the non modifiable risk factors age, C-reactive protein, and nephropathy in multivariable analyses. CONCLUSION: These data imply that multi-morbid elderly PAD patients still benefit by intensified specialist care compared to the usual primary care setting. KEY MESSAGES Center-based patient care improves survival in patients with peripheral arterial disease; mortality was reduced from 82 to 21 events per 1000 patient-years (rate ratio 0.26). Mortality was related to age (HR 1.46), CRP (HR 1.36), and nephropathy (HR 2.7). A multifactorial approach combining adequate drug prescription, accomplishment of agreed goals and repetitive training to initiate, implement, and persist treatment adaptations was applied. PMID- 27665939 TI - UGT2B28 genomic variation is associated with hepatitis B e-antigen seroconversion in response to antiviral therapy. AB - Seroconversion of hepatitis B virus (HBV) e-antigen (HBeAg) is a critical but often-missed therapeutic goal in standard antiviral treatments. An extreme phenotype genome-wide association study was performed, comparing untreated spontaneous recoverers (with seroconversion of HBV surface antigen) versus entecavir-treated patients failing to achieve HBeAg seroconversion. A single nucleotide-polymorphism rs2132039 on the UGT2B28 gene, alongside an adjacent copy number polymorphism (CNP605), manifested the strongest clinical associations (P = 3.4 * 10-8 and 0.001, respectively). Multivariate analysis showed that rs2132039 TT genotypes, but not CNP605 copy numbers, remained associated to spontaneous recoverers (P = 0.009). The clinical association of rs2132039 was validated successfully in an independent cohort (n = 302; P = 0.002). Longitudinal case only analyses revealed that the rs2132039-TT genotype predicted shorter time-to HBeAg-seroconversion in all antiviral-treated patients (n = 380, P = 0.012), as well as the peginterferon-treated subgroup (n = 123; P = 0.024, Hazard ratio [HR] = 2.104, Confidence interval [CI] = 1.105-4.007). In the entecavir-treated subgroup, the predictive effect was restricted by pretreatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, with effective prediction observed in patients with ALT < 200 IU/ml and ALT/AST ratio <2 (n = 132; P = 0.013, HR = 10.538, CI = 1.420-78.196). PMID- 27665940 TI - Effect of time on recovery of plasma microsamples for the quantitative determination of vancomycin. AB - The reliability of extraction recovery of an analyte in bioanalysis is fundamentally important for downstream analytical testing. For dried format microsamples, if the recovery changes with time the concentration in clinical samples, derived from calibration standards and alongside quality control samples prepared following different drying protocols, may not reflect the true result. The purpose of this paper was therefore to evaluate changes to extraction recovery across time for one analyte, the glycopeptide antibiotic vancomycin, in plasma using two dried microsampling formats, dried plasma spots and volumetric absorptive microsampling. PMID- 27665941 TI - Randomized controlled trial of a web-based multi-modal therapy program for executive functioning in children and adolescents with unilateral cerebral palsy. AB - : Purpose state: Determine the efficacy of Move-it-to-improve-it (MitiiTM), a multi-modal web-based program, in improving Executive Function (EF) in children with unilateral cerebral palsy (UCP). METHOD: Participants (n = 102) were matched in pairs then randomized to: intervention (MitiiTM for 20 weeks; n = 51; 26 males; mean age = 11 years 8 months (SD = 2 years 4 months); Full Scale IQ = 84.65 (SD = 15.19); 28 left UCP; GMFCS-E&R (I = 20, II = 31) or waitlist control (n = 50; 25 males; mean age = 11 years 10 months (SD = 2 years 5 months); Full Scale IQ = 80.75 (SD = 19.81); 20 left UCP; GMFCS-E&R (I = 25, II = 25). MitiiTM targeted working memory (WM), visual processing (VP), upper limb co-ordination and physical activity. EF capacity was assessed: attentional control (DSB; WISC IV); cognitive flexibility (inhibition and number-letter sequencing DKEFS); goal setting (D-KEFs Tower Test); and information processing (WISC-IV Symbol Search and Coding). EF performance was assessed via parent report (BRIEF). Groups were compared at 20 weeks using linear regression (SPSS 21). RESULTS: There were no significant between group differences in attentional control (DSB; p = 0.20;CI= 0.40,1.87); cognitive flexibility (Inhibition, p = 0.34; CI= -0.73,2.11; number/letter sequencing, p = 0.17; CI= -0.55,2.94); problem solving (Tower; p = 0.28; CI= -0.61,2.09), information processing (Symbol; p = 0.08; CI= -0.16, 2.75; Coding; p = 0.07; CI= -0.12,2.52) or EF performance (p = 0.13; CI= -10.04,1.38). CONCLUSION: In a large RCT, MitiiTM did not lead to significant improvements on measures of EF or parent ratings of EF performance in children with UCP. Implications for rehabilitation A large RCT of the multi-modal web based training; Move It to Improve It (MitiiTM) improves motor processing, visual perception, and physical capacity but does demonstrate statistically significant improvements or clinical significance in executive function in children with mild to moderate unilateral cerebral palsy (UCP). MitiiTM training completed by an intervention group was highly variable with few children reaching the target dosage of 60 h. Technical issues including server and internet connectively problems lead to disengagement with the program. Web-based training delivered in the home has the potential to increase therapy dose and accessibility, however, MitiiTM needs to be tailored to include tasks involving goal-setting, more complex problem solving using multi-dimensional strategies, mental flexibility, switching between two cognitively demanding tasks, and greater novelty in order to increase the cognitive component and challenge required to drive changes in EF. PMID- 27665942 TI - CYR61 suppresses growth of human malignant melanoma. AB - Cysteine-rich protein 61 (CCN1/CYR61) is an important marker of proliferation and metastasis in malignant melanoma, making it a potential target for melanoma treatment. In this study, we compared the expression of CRY61 in Chinese patients with malignant melanoma with its expression in patients with other skin tumors or with no skin pathological conditions. We examined the effects of anti-human CYR61 monoclonal antibody on proliferation and evaluated the changes in CYR61 expression and cell proliferation in response to treatment with either epirubicin or interferon (IFN)-alpha. CYR61 was expressed at lower levels in patients with malignant melanoma than in patients with other skin tumors or with no pathology. Following the treatment of B16 cells with epirubicin and IFN-alpha, CYR61 levels increased, cell growth was inhibited, and proliferating cell nuclear antigen expression decreased. Thus, CYR61 could become a therapeutic target for malignant melanoma patients with high CYR61 expression. PMID- 27665943 TI - Phonon thermal conduction in novel 2D materials. AB - Recently, there has been increasing interest in phonon thermal transport in low dimensional materials, due to the crucial importance of dissipating and managing heat in micro- and nano-electronic devices. Significant progress has been achieved for one-dimensional (1D) systems, both theoretically and experimentally. However, the study of heat conduction in two-dimensional (2D) systems is still in its infancy due to the limited availability of 2D materials and the technical challenges of fabricating suspended samples that are suitable for thermal measurements. In this review, we outline different experimental techniques and theoretical approaches for phonon thermal transport in 2D materials, discuss the problems and challenges of phonon thermal transport measurements and provide a comparison between existing experimental data. Special attention will be given to the effects of size, dimensionality, anisotropy and mode contributions in novel 2D systems, including graphene, boron nitride, MoS2, black phosphorous and silicene. PMID- 27665944 TI - Consumption of Dietary Resistant Starch Partially Corrected the Growth Pattern Despite Hyperglycemia and Compromised Kidney Function in Streptozotocin-Induced Diabetic Rats. AB - We previously demonstrated that feeding of dietary resistant starch (RS) prior to the induction of diabetes delayed the progression of diabetic nephropathy and maintained vitamin D balance in streptozotocin (STZ)-induced type 1 diabetic (T1D) rats. Here, we examined the impact of RS on kidney function and vitamin D homeostasis following STZ injection. Male Sprague-Dawley rats were administered STZ and fed a standard diet containing cornstarch or 20, 10, or 5% RS for 4 weeks. T1D rats fed 10 and 20% RS, but not 5% RS, gained more weight than cornstarch-fed rats. Yet, renal health and glucose metabolism were not improved by RS. Our data suggest that RS normalized growth patterns in T1D rats after diabetes induction in a dose-dependent manner despite having no effect on blood glucose and vitamin D balances. Future interventions should focus on the preventative strategies with RS in T1D. PMID- 27665945 TI - Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis. AB - Hepatocellular carcinoma is the most prevalent type of tumor among primary tumors affecting the liver. Rapamycin is currently used as a basis for chemotherapy in the treatment of cancers, including the liver. Because it shows several adverse effects, minimizing these effects without compromising efficacy is important. In this sense other drugs may be used concomitantly. One of these drugs is fructose 1,6-bisphosphate (FBP), which has shown therapeutic effect in various pathological situations, having antioxidant and anti-inflammatory proprieties. The objective of the present study was to evaluate the activity of rapamycin in combination with the FBP in HepG2 cell proliferation and the mechanisms involved. HepG2 cells were analyzed after 72 h of treatment with both drugs. Cell proliferation, cytotoxicity, cytokines, apoptosis, senescence, autophagy and oxidative stress were accessed. Iotat was demonstrated that the combination is more efficient than the single use of substances, because subtherapeutic doses of rapamycin, when associated to FBP become effective, reducing cell proliferation, through a significant increase in the production of tiobarbituric acid reactive substances (TBARS), suggesting that this might be the cause of death by apoptosis. According to these results, we believe that the association of both drugs may be a promising choice for the treatment of hepatocarcinoma. PMID- 27665946 TI - Common genetic heterogeneity of human interleukin-37 leads to functional variance. AB - Interleukin-37 (IL-37) is an inhibitory member of the IL-1 family of cytokines. We previously found that balanced selection maintains common variations of the human IL37 gene. However, the functional consequences of this selection have yet to be validated. Here, using cells expressing exogenous IL-37 variants, including IL-37 Ref and IL-37 Var1 and Var2, we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation. The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1, despite the comparable mRNA levels of all three variants. Further study showed that IL-37 Var2 was rapidly degraded by a proteasome dependent mechanism mediated by enhanced polyubiquitination, leading to a transient upregulation of IL-37 Var2 after immune stimulation. Finally, when ectopically expressed in cells, human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants. Conversely, purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro. In conclusion, our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies, primarily as a result of differences in IL-37 protein stability, suggesting the possible involvement of these variants in various human diseases. PMID- 27665948 TI - Variability in the anterior extralaryngeal branch of the recurrent laryngeal nerve: clinical implications. AB - BACKGROUND: This study aimed to identify the anterior and posterior extralaryngeal branches (AELB, PELB) of the recurrent laryngeal nerve (RLN), measure these branches when present, and determine relationships between gender, sidedness and neck length. MATERIALS AND METHODS: Dissection was completed to level of the thyroid on 45 cadavers. The course of the RLN was then traced superiorly from its entry into the neck. Careful reflection of the thyroid and dissection of the lateral thyroid ligament permitted visualisation of the full course of the nerve. If extralaryngeal branching (ELB) was present, measurements were taken from the point of bifurcation of the RLN to the point of laryngeal entry through the cricothyroid membrane. Neck measurements, from the spinous process of C7 to the superior nuchal line, were taken. Gender of the specimen was noted. Data was analysed in SPSS. RESULTS: Extralaryngeal branching was found in 77.78% of our sample, 77.14% on the left and 54.29% on the right. A significant difference was found between AELB length on the left and right, indicating that the left branch will be longer than the right when present. A significant difference in neck length between those with and without ELB was also found, indicating that people with longer necks more often display ELB. Neither neck length and AELB length, nor gender and AELB length were strongly correlated in this sample. CONCLUSIONS: Extralaryngeal branching can occur in all populations, but there are definite trends in its incidence and length. Surgeons should be aware of these trends before operating on patients. PMID- 27665949 TI - Morphometric analysis of the mandible in the Durban Metropolitan population of South Africa. AB - BACKGROUND: The identification of an individual from skeletal remains plays a vital role in forensic investigation as it is essential for the identification of the individual's age, sex, and/or race and further analysis. Skeletal characteristics differ from one population group to another since population specific osteometric standards exist for sex determination. Since the mandible is the largest, strongest and most durable compact facial bone, it is the best preserved after death. While sexual dimorphism of the mandible is indicated by its shape and size, morphometric analysis is more accurate in the determination of sex from the skull. The aim of this study was to evaluate the morphometric parameters of the mandible in the Durban Metropolitan population. MATERIALS AND METHODS: Various morphometric parameters of the mandible were measured and assessed in 265 digital panoramic radiographs aged between 16 and 30 years (n = 530). Each parameter recorded was statistically analysed using SPSS to determine if a relationship existed between the parameter, and sex and age. RESULTS: In this study the morphometric parameters of the male mandibles were greater than that of the females. This concurred with the findings of previous studies. The length of the mandibular ramus on the right and left sides was statistically significant with sex. CONCLUSIONS: This correlated with previous studies, indicating that the length of the mandibular ramus generally has higher sexual dimorphism than any other morphometric mandibular parameter (p = 0.000). However, only the length of the right mandibular body was statistically significant when compared with sex (p = 0.040). The findings of this study may assist forensic investigators, anatomists, anthropologists and maxillo-facial surgeons. PMID- 27665950 TI - Imaging topography and morphometry of persistent left superior caval vein and its variations, detected on cardiac implantable electronic device implantation. AB - BACKGROUND: Persistent left superior caval vein (PLSCV) is a rare, anatomically diverse developmental anomaly of systemic veins. Clinically asymptomatic PLSCVs are detected incidentally during medical procedures that utilise systemic veins, such as cardiac implantable electronic device (CIED) placement, and whose successful completion depends on favourable morphometric parameters of these vessels. The aim of this paper was to present topography and morphometry of PLSCV variations encountered during CIED implantation procedures. MATERIALS AND METHODS: We analysed a group of 5,010 patients for detection of PLSCV during de novo CIED implantation procedures with transvenous lead placement in the years 2003-2015. PLSCVs were detected intraprocedurally based on venographic images illustrating the venous anomaly and its morphometric parameters, and were subsequently confirmed via postoperative diagnostics. RESULTS: PLSCVs were detected in 10 patients (mean age 66.0 +/- 14.0 years; 5 females and 5 males), who constituted 0.2% of the analysed group. There were 6 cases of double superior vena cava (DSVC), 3 of which had a brachiocephalic vein (BCV) connection and did not have BCV bridging. Four patients with a PLSCV had right superior vena cava agenesis; this very rare variation is known as 'single PLSCV'. All of the detected PLSCV variations drained into the right atrium via the coronary sinus. CONCLUSIONS: Our data from a period of 13 years illustrate how rare the PLSCV type venous anomaly is. The three distinct anatomical PLSCV types showed inter individual morphometric variations. Due to asymptomatic nature of this anomaly, all cases were detected incidentally, during CIED implantation procedures. PMID- 27665947 TI - Contribution and underlying mechanisms of CXCR4 overexpression in patients with systemic lupus erythematosus. AB - Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected. Involvement of phosphatidylinositol 3 kinase (PI3K)/Akt and Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathways was assessed by adding blocking agents Ly294002 and AG490. Since CD63 is reported to mediate endosomal recruitment of CXCR4 and BCL6 is capable of silencing CD63 gene transcription, we also measured BCL6 and CD63 gene transcription with real-time PCR. It was shown that CXCR4 expression on B cells was significantly upregulated in SLE patients, especially in those with lupus nephritis, and was positively correlated with SLE Disease Activity Index scores and negatively with the serum complement 3 levels (P<0.05). Downregulation of CXCR4 by IL-21 was intact. In contrast, a similar effect of aIgM plus CD40L in downregulating CXCR4 expression was defective in SLE patients but was restored by co-stimulation with IL-21 in vitro. Both Ly294002 and AG490 promoted downregulation of surface CXCR4 expression on B cells from SLE patients (P=0.078 and P=0.064). Furthermore, B cells from SLE patients exhibited diminished CD63 mRNA and enhanced BCL6 mRNA expression (both P<0.05). To sum up, CXCR4 was overexpressed on SLE B cells, positively correlating with disease activity and kidney involvement. Overactivation of the PI3K/Akt and JAK/STAT pathways as well as defective CD63 synthesis may contribute to CXCR4 dysregulation in SLE. PMID- 27665951 TI - Inhibition of inducible nitric oxide synthase (iNOS) by simvastatin attenuates cardiac hypertrophy in rats. AB - BACKGROUND: The left ventricular hypertrophy (LVH) occurs in response to the haemodynamic overload in some physiological and pathological conditions. This study was designed to investigate the possible cardioprotective effect of simvastatin (SIM) treatment against isoproterenol (ISO)-induced LVH and the probable underlying mechanism in adult male Wistar rats. MATERIALS AND METHODS: Animals were allocated into four groups. Rats of control group received normal saline orally for 30 days and intraperitoneally for the last 7 days. Rats of SIM group received SIM orally (10 mg/kg/day in saline) for 30 days. Rats of ISO group received normal saline orally for 30 days and ISO intraperitoneally (5 mg/kg) for the last 7 days to induce LVH. Rats of ISO/SIM group received SIM for 30 days and ISO intraperitoneally for the last 7 days. At the end of the experiment, all animals were sacrificed by cervical decapitation under anaesthesia. Truncal blood was collected and serum was separated and used for biochemical assay. The heart was dissected and processed for histological and immunohistochemical studies. RESULTS: The results of the present study confirmed the ISO-induced myocardial lesions including significant increase of heart weight (HW), heart weight/body weight (HW/BW) ratio, LVH, interstitial myocardial fibrosis (increased collagen types I and III), inflammatory cellular infiltration, necrosis of cardiomyocytes, and increased expression of inducible nitric oxide synthase (iNOS) and thioredoxin in cardiomyocytes. These changes were accompanied by significant increase in serum levels of troponin-T, creatine phosphokinase-MB (CPK-MB), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Co administration of SIM to ISO-injected rats significantly reduced all these cardiac changes and serum biochemical markers in addition to marked depletion of iNOS and thioredoxin expression in cardiomyocytes. CONCLUSIONS: It is concluded that SIM co-administration attenuated ISO-induced cardiac lesions including LVH by inhibiting iNOS expression in cardiomyocytes. PMID- 27665953 TI - Anatomical variations of median nerve formation, distribution and possible communication with other nerves in preserved human cadavers. AB - Formation, distribution and possible communication of the median nerve are essential to know in treatment and surgeries of various conditions of injuries e.g. repair or reconstruction of the median nerve post traumatic accident. In the present study, 44 upper limbs were dissected. Root forming the median nerve, the median nerve in relation with the axillary artery and communication of the median nerve with other nerves were noted. PMID- 27665952 TI - The myloglossus in a human cadaver study: common or uncommon anatomical structure? AB - BACKGROUND: Additional extrinsic muscles of the tongue are reported in literature and one of them is the myloglossus muscle (MGM). Since MGM is nowadays considered as anatomical variant, the aim of this study is to clarify some open questions by evaluating and describing the myloglossal anatomy (including both MGM and its ligamentous counterpart) during human cadaver dissections. MATERIALS AND METHODS: Twenty-one regions (including masticator space, sublingual space and adjacent areas) were dissected and the presence and appearance of myloglossus were considered, together with its proximal and distal insertions, vascularisation and innervation. RESULTS: The myloglossus was present in 61.9% of cases with muscular, ligamentous or mixed appearance and either bony or muscular insertion. Facial artery provided myloglossal vascularisation in the 84.62% and lingual artery in the 15.38%; innervation was granted by the trigeminal system (buccal nerve and mylohyoid nerve), sometimes (46.15%) with hypoglossal component. CONCLUSIONS: These data suggest us to not consider myloglossus as a rare anatomical variant. PMID- 27665954 TI - An evaluation of the posterior cruciate ligament function in total knee arthroplasty with regard to its morphology and clinical properties. AB - The aim of the study was to determine the degree of posterior cruciate ligament (PCL) degeneration and the reduction in the number of its mechanoreceptors, in patients with advanced degenerative joint disease. PCLs taken from study group of 50 patients in the mean age of 70.7 (53-84) years with a diagnosis of advanced idiopathic osteoarthritis undergoing condylar total knee arthroplasty were compared to those taken form the control group of 10 knee joints of cadavers. Groups were matched with regard to sex and age. Histological examination of PCLs of the study group showed changes of an inflammatory process and no significant signs of osteoarthritis in the control group. A close correlation was found between the severity of degenerative changes on the X-ray images according to the Ahlback scale, and the increased mucoid degeneration (p < 0.0001), the severity of the degeneration of the collagen structure (p < 0.0001) and the presence of proprioceptors of PCLs (p < 0.0001). Conserving the PCL by the use of type cruciate retaining knee arthroplasty does not guarantee the preservation of correct proprioceptive sensation. PMID- 27665955 TI - A new insight into the fabella at knee: the foetal development and evolution. AB - Using longitudinal semiserial sections of 12 lower extremities from 8 human foetuses at 15-18 weeks, we compared foetal morphologies of the knee in specimens with and without fabellae. We also compared the fabella, if present, with the hallucal sesamoid in the same foetus. Cartilaginous fabella, positive for versican and tenascin by immunohistochemistry, was found in 5 of the 8 foetuses. This structure was embedded in a thick and tight lateral fibrous band, providing a common origin of the plantaris muscle and the lateral head of the gastrocnemius muscle. The plantaris was covered by the lateral head of the gastrocnemius, but these 2 muscles were separated by a distinct fascia or space. Notably, the foetal fabella did not attach to the joint capsule. In the 3 specimens without fabellae, the lateral fibrous band was thin, containing a fibrous mass, negative for versican and tenascin, in place of the fabella. The "medial" head of the gastrocnemius faced or covered the plantaris, while the lateral head was continuous with the plantaris. A hallucal cartilaginous sesamoid, positive for versican and tenascin, was present in all 8 specimens. It carried a flat surface facing the joint cavity and was covered by tendons of the short muscles of the foot. Because of the difference in topographical relation of muscles between specimens with or without fabella, rather than mechanical stress to the tendon, fabella development may require a distinct plantaris muscle independent of the gastrocnemius. We discussed about an evolutionary aspect of the fabella and plantaris muscle. PMID- 27665956 TI - An arthroscopic evaluation of the anatomical "critical zone". AB - BACKGROUND: The "critical zone", a region of speculated vascularity, is situated approximately 10 mm proximal to the insertion of the supraspinatus tendon. Despite its obvious role as an anatomical landmark demarcator, its patho-anatomic nature has been identified as the source of rotator cuff pathology. Although many studies have attempted to evaluate the vascularity of this region, the architecture regarding the exact length, width and shape of the critical zone, remains unreported. This study aimed to determine the shape and morphometry of the "critical zone" arthroscopically. MATERIALS AND METHODS: The sample series, which was comprised of 38 cases (n = 38) specific to pathological types, employed an anatomical investigation of the critical zone during routine real-time arthroscopy. Demographic representation: i) sex: 19 males, 19 females; ii) age range: 18-76 years; iii) race: white (n = 29), Indian (n = 7) and coloured (n = 2). RESULTS: The incidence of shape and the mean lengths and widths of the critical zone were determined in accordance with the relevant demographic factors and patient history. Although the cresenteric shape was predominant, hemispheric and sail-shaped critical zones were also identified. The lengths and widths of the critical zone appeared markedly increased in male individuals. While the increase in age may account for the increased incidence of rotator cuff degeneration due to poor end-vascular supply, the additional factors of height and weight presented as major determinants of the increase in size of the critical zone. CONCLUSIONS: In addition, the comparisons of length and width with each other and shape yielded levels of significant difference, therefore indicating a directly proportional relationship between the length and width of the critical zone. This detailed understanding of the critical zone may prove beneficial for the success of post-operative rotator cuff healing. PMID- 27665957 TI - An anatomical investigation of the superficial and deep palmar arches. AB - BACKGROUND: The superficial palmar arch (SPA) and deep palmar arch (DPA) provide the dominant vascular supply to the hand. The SPA is considered to be highly variable and can be classified as either complete or incomplete. The simplest definition states that the anastomosis between the vessels contributing to the arch represent a complete arch, while an incomplete arch is described as characterised by an absence of anastomosis between the vessels contributing to it. This study aimed to describe the anatomical landmarks, formation and branching patterns of the SPA and DPA. In this study, the SPA and DPA were dissected in 50 specimens (n = 100 adult hands), respectively. MATERIALS AND METHODS: A complete SPA was observed in 92% of specimens and classified into three types. In Type A (44%), the SPA was formed by the anastomosis of the superficial palmar branch of the radial artery with the ulnar artery. Type B (46%) was formed by the ulnar artery alone and Type C (2%) was formed by anastomosis of the ulnar artery with the superficial palmar branch of the radial artery and the persistent median artery. RESULTS: An incomplete SPA was observed in 8% of the specimens and divided into three types formed by the radial and ulnar arteries. The DPA was divided into five types viz. Type G (72%), where the DPA was formed by anastomosis of the deep palmar branch of the radial artery (DPBRA) with the deep palmar branch of the ulnar artery (DPBUA). Type H (12%), was formed by anastomosis of the DPBRA, the DBUA and the interosseous artery. Type I (8%), was formed by the anastomosis of the DPBRA with the superior and inferior DPBUA. Type J (4%), the deep ulnar artery had two branches whereby either one branch anastomosed with the DPBRA to form the DPA. Type K (4%), the DBUA exhibited two deep branches with one branch anastomosing with the DPBRA to complete the DPA. CONCLUSIONS: The interosseous artery anastomosed with either the DPA or the additional DPBUA. Knowledge of the variability of the SPA and DPA is crucial for safe and successful hand surgeries. PMID- 27665958 TI - Coronary artery dominance dependent collateral development in the human heart. AB - BACKGROUND: In obstructive coronary artery disease, coronary collateral arteries serve as alternative conduits for blood flow to the myocardial tissue supplied by the obstructed vessel(s). Therefore, they are a "natural coronary arterial bypass" to the region supplied by the obstructed vessels. This study aims to determine the influence of demographic and morphologic coronary arterial factors on coronary collateral development in coronary arterial obstruction. MATERIALS AND METHODS: The study group was selected from the coronary angiographic records of 2029 consecutive patients (mean age: 59 +/- 12 years). Coronary collaterals were graded from 0 to 3 based on the collateral connection between the donor and recipient arteries. The angiograms of the patients (n = 286) with total obstruction of the coronary arteries were selected for analysis. RESULTS: There were no significant association between patients' age and sex and the formation of excellent collaterals. However, the location of atherosclerotic lesion affected collateral development in the right coronary artery. In addition, the right coronary arterial dominant pattern significantly influenced the formation of excellent coronary collaterals. CONCLUSIONS: Coronary collateral arteries are better developed in right dominant pattern. It may be concluded that coronary arterial morphological pattern influences coronary collateral artery development. PMID- 27665959 TI - The relationship between the dimensions of the internal auditory canal and the anomalies of the vestibulocochlear nerve. AB - BACKGROUND: Internal auditory canal (IAC) stenosis and vestibulocochlear nerve (VCN) abnormalities have been reported to be associated with sensorineural hearing loss. Previous studies classified the normal dimensions of the IAC and its anomalies with no consideration of the VCN. Other studies categorised the VCN development in only stenotic canals. In the present study, an anatomical classification of the normal dimensions of the IAC and its anomalies and their association with malformations of the VCN and its subdivisions were described. MATERIALS AND METHODS: Retrospective review was undertaken for children ranged from 1 to 10 years. A total of 764 canals were investigated for pre-operative assessment of cochlear implantation. Other 100 canals of normal hearing ears were included as the control group. The maximum anteroposterior diameter, considered the width of the canal, was measured in axial plane and the length of the canal was identified in coronal plane. The canals were categorised normal: if they are from 3 to 8 mm, patulous: if they are more than 8 mm, stenotic: if they are less than 3 mm and atretic if absent, using multislice computed tomography. The VCN trunks and their subdivisions were investigated using magnetic resonance imaging. RESULTS: Internal auditory canals were found normal in 66% with a mean width: 5.27 +/- +/- 0.68, patulous in 17% with a mean width 113% more than that of the control group (p = 0.000), stenotic in 13% with a mean width 73% less as compared to that of the control group (p = 0.000) and atretic in 4% of the experimental canals. The VCN trunks were found normal with well-developed subdivisions in 77.8% of the normal canals, 98.4% of the patulous canals, and 19.2% of the stenotic canals. The VCN trunks were normal with hypoplastic subdivisions in 11.3% of the normal canals, 1.6% in the patulous canals, and 61.6% in the stenotic canals with a mean width 52% less than that of the normal trunk with developed subdivisions. Hypoplastic VCN trunks with absent subdivisions were reported in 7.3% of the normal canals, 11.1% of the stenotic canals and in 3.2% of the atretic canals. The VCN trunks were not found in 3.6% of the normal canals, in 8.1% of the stenotic canals and in 96.8% of the atretic canals. CONCLUSIONS: Internal auditory canal formation was dependent on the process of development and growth of the eighth cranial nerve and its subdivisions that greatly affected the completion of IAC canalisation. This paper could serve as a reference providing a quantitative classification of the relationship between the dimensions of the IAC and the development of the VCN trunk and its subdivisions. PMID- 27665960 TI - Congenital coronary artery anomalies in adult population detected using dual source ECG-gated CTA in a single institution. AB - BACKGROUND: Congenital anomalies of the coronary arteries (CAs) are rare and are often diagnosed incidentally during a conventional coronary angiography. Recently, the incidence of these congenital defects is on the rise particularly after the introduction of the electrocardiography (ECG) gated coronary computed tomographic angiography (CCTA). This innovative radiological screening modality has led to the most precise mapping of the course of the CAs on computed tomographic scan. The aim of the study is to determine the prevalence and describe the CAs congenital anomalies and their variations in Kuwaiti population at a single institution experience. MATERIALS AND METHODS: We analysed the CCTA data obtained consecutively from 842 patients (2013-2014), retrospectively. The inclusion criteria for patients' selection were: atypical chest pain, equivocal ECG, assessment of patency of coronary stents or grafts and pre-operative screening. Information was acquiesced using a dual-source CT scanner with ECG gating. RESULTS: Data analysis revealed that 22 (2.61%) patients were found to have CA anomalies out of the 842 patients who underwent CCTA. Out of these CA anomalies, 13 cases showed more than two ostia, 7 cases showed the ectopic origin of a CA from opposite sinus or non-aortic sinus, 2 cases showed single coronary ostium and 1 case showed coronary artery with pulmonary fistula. Also, myocardial bridging was identified in 78 (9.26%) patients whereas ramus intermedius branch was identified in 160 (19%) patients. CONCLUSIONS: The prevalence of CA anomalies in Kuwait was 2.6%, which is relatively higher than previously reported studies from different countries. PMID- 27665961 TI - Dens invagination and root dilaceration in double multilobed mesiodentes in 14 year-old patient with anorexia nervosa. AB - This paper describes a rare case of erupted double supernumerary teeth with unusual morphology in a 14-year-old patient with an eating disorder. The coexistence of dental morphological anomalies: multilobed mesiodens, multiple dens in dente of different types and root dilaceration have not been previously reported. The paper highlights anatomical and radiological aspects of dental abnormalities and clinical implications of delayed treatment. PMID- 27665962 TI - Erratum to "Non-surgical treatment of localized rectal cancer is an experimental option". PMID- 27665963 TI - MicroRNA-138 inhibits migration and invasion of non-small cell lung cancer cells by targeting LIMK1. AB - MicroRNA (miR)-138 has previously been demonstrated to have a suppressive role in numerous types of human cancer, including non-small cell lung cancer (NSCLC). LIM domain kinase 1 (LIMK1) is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of cofilin. Previous studies have reported that LIMK1 is associated with NSCLC; however, the underlying regulatory mechanism of LIMK1, and the association between LIMK1 and miR-138 in NSCLC cells, remains largely unknown. The present study aimed to reveal the regulatory roles of miR-138 and LIMK1 in NSCLC cell migration and invasion. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to examine the mRNA and protein expression levels. Transwell and wound healing assays were conducted to determine cell invasion and migration. A luciferase reporter assay was used to determine the target association between miR-138 and LIMK1. The present study demonstrated that miR-138 was markedly downregulated in NSCLC tissues and cell lines, whereas the expression levels of LIMK1 were significantly upregulated. LIMK1 was further identified as a direct target of miR-138 in NSCLC H460 cells. Furthermore, overexpression of miR-138 significantly inhibited the protein expression of LIMK1, whereas knockdown of miR 138 upregulated the protein expression of LIMK1 in H460 cells. In addition, overexpression of miR-138 significantly inhibited the migration and invasion of NSCLC cells; however, overexpression of LIMK1 significantly promoted NSCLC cell migration and invasion. An investigation into the underlying molecular mechanism revealed that overexpression of miR-138 significantly decreased cofilin signaling activity, whereas knockdown of miR-138 notably enhanced cofilin signaling activity. In conclusion, the present study suggests that miR-138 may inhibit the migration and invasion of NSCLC cells by targeting the LIMK1/cofilin signaling pathway. Therefore, miR-138/LIMK1/cofilin may be considered a potential therapeutic target for the treatment of NSCLC. PMID- 27665965 TI - Department of Error. PMID- 27665966 TI - Sulfate-Incarcerating Nanojars: Solution and Solid-State Studies, Sulfate Extraction from Water, and Anion Exchange with Carbonate. AB - A series of 9 homologous sulfate-incarcerating nanojars [SO4?{Cu(OH)(pz)}n]2- (Cun; n = 27-33; pz = pyrazolate), based on combinations of three [Cu(OH)(pz)]x rings (x = 6-14, except 11)-namely, 6 + 12 + 9 (Cu27), 6 + 12 + 10 (Cu28), 8 + 13 + 8 (Cu29), 7 + 13 + 9 (Cu29), 8 + 14 + 8 (Cu30), 7 + 14 + 9 (Cu30), 8 + 14 + 9 (Cu31), 8 + 14 + 10 (Cu32), and 9 + 14 + 10 (Cu33)-has been obtained and characterized by electrospray-ionization mass spectrometry (ESI-MS), variable temperature 1H NMR spectroscopy, and thermogravimetry. The X-ray crystal structure of Cu29 (8 + 13 + 8) is described. Cu32 and Cu33, which are the largest nanojars in this series, are observed for the first time. Despite extensive overlap at a given temperature, monitoring the temperature-dependent variation of paramagnetically shifted pyrazole and OH proton signals in 60 different 1H NMR spectra over a temperature range of 25-150 degrees C and a chemical shift range from 41 ppm to -59 ppm permits the assignment of individual protons in six different sulfate nanojars in a mixture. As opposed to ESI-MS, which only provides the size of nanojars, 1H NMR offers additional information about their detailed composition. Thus, nanojars such as Cu29 (8 + 13 + 8) and Cu29 (7 + 13 + 9) can easily be differentiated in solution. High-temperature solution studies unveil a significant difference in the thermal stability of nanojars of different sizes obtained under kinetic control at ambient temperature, and aid in predicting the structure of the Cu33 nanojar, as well as in explaining the absence of the Cu11 ring from the Cu6-Cu14 series. Anion exchange studies using sulfate and carbonate reveal that, although each anion is thermodynamically preferred by a nanojar of a certain size, the exchange of an already incarcerated anion is hampered by a substantial kinetic barrier. The remarkably strong binding of anions by nanojars allows for the extraction of highly hydrophilic anions, such as sulfate and carbonate, from water into organic solvents, despite their very large hydration energies. PMID- 27665964 TI - Aquagenic wrinkling of the palms: a diagnostic clue to cystic fibrosis carrier status and non-classic disease. PMID- 27665967 TI - Cytotoxic effects of bulk fill composite resins on human dental pulp stem cells. AB - Five bulk fill composite resins, including SDR, Tetric EvoCeram Bulk Fill (TEC), X-trafil (XTF), Sonic Fill (SF), Filtek Bulk Fill (FBF), were used in this study. Human dental pulp stem cells were cultured in 12-well culture dishes (3 * 104 cells per cm(2)) and stored in an incubator at 37 degrees C and 5% CO2 for 1 day. On days 1, 7, 14, and 21 of co-culture, viable cells were measured using a WST-1 assay. Lower cell viability was observed with XTF and SDR bulk fill composite resins compared to the control group during the WST-1 assay. Although bulk fill composite resins provide advantages in practical applications, they are limited by their cytotoxic properties. (J Oral Sci 58, 299-305, 2016). PMID- 27665968 TI - Gene expression changes in bioceramic paste-treated human dental pulp cells. AB - We evaluated the gene expression profiles of human dental pulp cells exposed to iRoot BP using microarray after 24 and 72 h. The results were verified using quantitative reverse transcriptase PCR analysis. Of the 36,000 transcripts arrayed, 21 were up-regulated and 15 were down-regulated by more than two fold. The largest group of up-regulated genes included those involved in nucleobase containing compound metabolic processes, cell communication, protein metabolic processes, developmental processes, and biological regulation. The largest groups of down-regulated genes were those involved in cell communication, development, and biological regulation processes. In conclusion, iRoot BP affects the expression of genes involved in different biological processes in human dental pulp cells. (J Oral Sci 58, 307-315, 2016). PMID- 27665969 TI - Functional expression of TLR5 in murine salivary gland epithelial cells. AB - Toll-like receptors (TLR) recognize microbe-associated molecular patterns and induce the innate immune response. Among them, TLR5 recognizes the Gram-negative bacterial component flagellin. The aim of this study was to examine the expression of TLR5 in mouse salivary gland (SG). The SG was excised from 8- to 10 week-old female C57BL/6 mice. Salivary gland epithelial cells (SGECs) were purified and subjected to reverse transcription polymerase chain reaction (RT PCR). Western blotting was performed to detect TLR5 expression at the protein level in several organs. The localization of TLR5 in SG was examined using immunohistochemical staining. The responsiveness of SGECs to flagellin was further examined by evaluating the induction of CXCL1 by real-time PCR and immunoprecipitation followed by Western blotting. TLR5 expression in SG was confirmed at the gene and protein levels. Immunohistochemical staining detected TLR5 in both acinic and ductal cells of the sublingual gland, but not in serous acinic cells of the submandibular gland. Although TLR5 was detected throughout the cytoplasm in ductal cells, positive staining was observed on the basal side of the mucous acinic cells. The purified SGECs responded to flagellin and induced the production of CXCL1. These findings suggest that TLR5 is functionally expressed in the SG and responds to its cognate ligand flagellin. (J Oral Sci 58, 317-323, 2016). PMID- 27665970 TI - High-dose irradiation of bone chips preserves the in vitro activity of bone conditioned medium. AB - Extracorporeal irradiation sterilizes resected tumor bone used as autografts in reconstruction surgery. Therapeutic irradiation is a standard technique in head and neck cancer therapy that aims to preserve organ function. Bone irradiation has a complex, mostly inhibitory, effect on remodeling and regeneration, although the underlying mechanisms are still not fully understood. It remains unclear if extracorporeal irradiation affects the paracrine-like activity of the corresponding autografts. We recently reported that bone-conditioned medium from autogenous bone chips contains a number of factors that might affect cell activity. In the present study, we investigated the effects of extracorporeal irradiation of porcine cortical bone chips on the activity of the corresponding bone-conditioned medium. The effects of bone-conditioned medium on the expressions of transforming growth factor-beta (TGF-beta) target genes in oral fibroblasts were assessed. Bone-conditioned medium from bone chips exposed to a total radiation dose up to 120 Gy did not affect expressions of TGF-beta target genes, including adrenomedullin, BTB/POZ domain-containing protein 11, proteoglycan 4, NADPH oxidase 4, and interleukin 11, in oral fibroblasts. In conclusion, bone irradiation does not alter the capability of the corresponding bone-conditioned medium to provoke a robust fibroblastic cell response in vitro. (J Oral Sci 58, 325-331, 2016). PMID- 27665972 TI - Fracture resistance of teeth with oval canal morphology restored using oval and circular posts. AB - The study aimed to evaluate the effects of different post morphologies and placement lengths on the fracture resistance of teeth with oval canal morphology that had been restored with crowns. Extracted mandibular premolars with similar dimensions were decoronated. After the root canal treatment, the teeth were mounted on acrylic blocks. Samples were randomly divided into four groups (n = 10 each). In groups C-10 and C-5, 10-mm- and 5-mm-long circular post spaces were created. In groups O-10 and O-5, 10-mm- and 5-mm-long oval post spaces were ultrasonically created. After post cementation, all specimens were restored with composite cores and prepared at height of 6 mm. Thereafter, all teeth were restored with crowns. After thermocycling, all specimens underwent fracture resistance testing. Oval posts and placement at 10-mm depth showed higher fracture resistance than circular posts and placement at 5-mm depth (P < 0.001). Increased post length and use of oval posts enhanced the fracture strength of teeth with oval canal morphology. Based on the results of this study, although the fracture resistance of teeth restored with crowns was enhanced by deep fiber post placement, the use of oval fiber post is recommended in cases where deep placement is impossible. (J Oral Sci 58, 339-345, 2016). PMID- 27665971 TI - Degree of conversion of a self-adhesive endodontic sealer when used as bulk material. AB - This study tested the null hypothesis that the opacity of RealSeal SE (RSSE) sealer makes light-curing inefficient, while the degree of conversion (DC) is similar regardless of curing method. Fourteen uniradicular teeth were sectioned at 15 mm from the apex. Root canals were instrumented using the Reciproc file system, bulk-filled with RSSE, and divided randomly into two groups (dual-cure or self-cure). DC was determined by micro-Raman spectroscopy at 24 h, 48 h, and 1 week after filling, at 6, 9, and 12 mm from the coronal end. Contrast ratio (Yb/Yw) was used to determine the opacity of the material. Descriptive statistics and nonparametric tests were used, and significance was defined as a P value of less than 0.05. Opacity was almost total by the first section, at 6 mm. In dual cure mode, DC values at 24 h were lower in the apical section (63.8%) than in the more coronal sections and were lower than in self-cured specimens (87.4%). Light curing of the coronal end did not improve DC. These differences remained at 48 h and 1 week. Only a small (2%) but significant increase in DC was observed in evaluations at 24 h and 1 week. (J Oral Sci 58, 333-338, 2016). PMID- 27665973 TI - Effectiveness of three methods for evaluating root canal anatomy of mandibular incisors. AB - This study compared the effectiveness of clinical observation, clinical microscopic observation, and tooth-clearing technique in determining the number of canals in mandibular incisors. Root canal ramifications were also analyzed. Using clinical and microscopic analyses, we determined the number of canal entrances in 277 mandibular incisors. In addition, tooth-clearing technique was used to determine the number of canals and frequency of ramifications in the samples. The kappa coefficient was used to compare the different methods with regard to frequency of canals. Most teeth had one canal entrance. The proportion of teeth with two canals was 23.5% by tooth-clearing analysis, 5.8% by clinical microscopy, and 1.1% by clinical analysis. A large number of samples had some type of ramification (40.1%), and most ramifications were present in teeth with two canals. The most frequent ramification was lateral canals (8.3%). Clinical microscopy improved identification of a second canal in mandibular incisors. However, it did not identify second canals in all teeth with two canals. (J Oral Sci 58, 347-351, 2016). PMID- 27665974 TI - Glycomic profile of the human parotid gland between 18th and 26th week of fetal development. AB - The formation of new and functional structural components of several organs, such as parotid glands, can be influenced by the glycocode. This study analyzed the glycobiology of parotid salivary gland tissue during fetal development using specific biochemical probes (lectins and antibodies). Eleven parotid gland samples from human fetuses were obtained from spontaneous abortions at 14-28 weeks of gestation, and tissue sections were analyzed for lectin histochemistry and immunohistochemistry. From the 18th to 26th week, Canavalia ensiformis agglutinin, wheat germ agglutinin, Ulex europaeus agglutinin-I, peanut agglutinin, Sambucus nigra agglutinin, and Vicia villosa agglutinin lectin staining were predominantly observed in the apical and/or basement membranes of the ducts and tubulo-acinar units. Moreover, the presence of galectin-1 was found in the membrane, cytoplasm, and nucleus of both structures. Conversely, Gal-3 and mucin-1 were restricted to the glandular ducts. The lectin staining pattern changed during the weeks evaluated. Nevertheless, the carbohydrate subcellular localization represented a key factor in the investigation of structural distribution profiles and possible roles of these glycans in initial parotid gland development. These findings are defined by their high biological value and provide an important base for the development of subsequent studies. (J Oral Sci 58, 353-360, 2016). PMID- 27665975 TI - Effect of age on bite force. AB - This study compared bite force in adults older than 60 years with that of young adults. The participants were 20 healthy adults (9 men) older than 60 years (median age, 66 years) and 44 healthy young adults (22 men; age range, 18-25 years; median age, 22 years) at the International Medical University, Malaysia. All participants had at least 20 teeth, and bite force was measured and evaluated using the Dental Prescale system. Average (SD) bite force was 420.5 (242.0) N for the older adults and 541.4 (296.3) N for the young adults. Although mean bite force was higher for the young adults, the difference was not significant. These findings suggest that bite force is unaffected by age in adults with adequate dentition. (J Oral Sci 58, 361-363, 2016). PMID- 27665976 TI - Effect of essential oils prepared from Thai culinary herbs on sessile Candida albicans cultures. AB - Although medicinal herbs with fungicidal effects have been ubiquitously employed in traditional medicine, such effects of culinary herbs and spices still have to be elucidated. Therefore, it is noteworthy to determine the antifungal efficacy of some edible herbs used in Thai cuisine against sessile Candida albicans cultures, and to inquire if they can be further utilized as naturally-derived antifungals. Fourteen essential oils extracted from Thai culinary herbs and spices were tested for their antifungal activity against C. albicans using the agar disk diffusion method followed by broth micro-dilution method for the determination of minimum inhibitory concentration (MIC) and minimum fungicidal concentration. The oils with potent antifungal effects against planktonic fungi were then assessed for their effect against sessile fungus (adherent organisms and established biofilm culture). MIC of the oils against sessile C. albicans was evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5 carboxanilide reduction assay. All selected culinary herbs and spices, except galangal, garlic, and turmeric, exhibited inhibitory effects on planktonic yeast cells. Cinnamon bark and sweet basil leaf essential oils exhibited potent fungicidal effect on planktonic and sessile fungus. Sessile MICs were 8-16 times higher than planktonic MICs. Consequently, both cinnamon bark and sweet basil leaf herbal oils seem to be highly effective anti-Candida choices. (J Oral Sci 58, 365-371, 2016). PMID- 27665977 TI - Comparison between ultrasonic irrigation and syringe irrigation in clinical and laboratory studies. AB - Ultrasonic irrigation and syringe irrigation were compared for their efficacy at cleaning root canal in vivo and in vitro. The in vivo study used 60 anterior teeth or premolars from 60 patients with periapical periodontitis who were randomly assigned to a syringe irrigation group (group S) or an ultrasonic irrigation group (group U). After instrumentation with a K-file using the step back technique, the two groups received ultrasonic or syringe irrigation using 40 mL of 2.5% NaOCl respectively, followed by conventional lateral compaction. The in vitro study used 60 extracted single-canal premolars, which were also divided into U and S groups, and underwent the same irrigation and compaction. Forty of them were evaluated histologically by light microscopy, and the remaining 20 by scanning electron microscopy. No difference in main root canal filling was observed between the U and S groups. Notably, group U had a larger number of obturated lateral canals than group S. Moreover, a smaller amount of organic debris and more open dentinal tubules were observed in the root canal in group U than in group S. Our findings suggest that ultrasonic irrigation has a greater capacity to clean instrumented root canals than syringe irrigation. (J Oral Sci 58, 373-378, 2016). PMID- 27665978 TI - Levels of vaspin and omentin-1 in gingival crevicular fluid as potential markers of inflammation in patients with chronic periodontitis and type 2 diabetes mellitus. AB - The aims of the present study were to determine the levels of vaspin and omentin 1 in gingival crevicular fluid (GCF) in patients with chronic periodontitis (CP) with and without type 2 diabetes mellitus (T2DM), and to evaluate GCF vaspin and omentin-1 levels after non-surgical periodontal therapy. The study included 60 subjects: 15 systemically and periodontally healthy individuals, 15 periodontally healthy patients with T2DM, 15 systemically healthy patients with CP, and 15 patients with both CP and T2DM. GCF and clinical periodontal parameters were examined at the baseline and 6 weeks after periodontal therapy. Levels of vaspin, omentin-1 and tumor necrosis factor-alpha (TNF-alpha) were measured by ELISA, and their relative ratios were calculated. GCF vaspin and TNF-alpha levels were significantly higher in the CP groups than in the periodontally healthy groups (P < 0.008) and decreased after therapy in the former (P < 0.025). GCF omentin-1 levels were significantly lower in the CP groups than in the periodontally healthy groups (P < 0.008) and increased after therapy in the former (P < 0.05). Statistically significant positive correlations were found between the total amount of vaspin and TNF-alpha, glycated hemoglobin (HbA1c), clinical attachment level and gingival index, whereas the level of omentin-1 was negatively correlated with these parameters in all groups (P < 0.05). We found that non surgical periodontal therapy influenced the GCF levels of both vaspin and omentin 1 in the CP groups. Our results suggest that the levels of vaspin and omentin-1 in GCF could have potential application as inflammatory markers of diabetes, periodontal disease and treatment outcome. (J Oral Sci 58, 379-389, 2016). PMID- 27665979 TI - Masticatory function, taste, and salivary flow in young healthy adults. AB - This study aimed to investigate masticatory function and taste and their possible relationship with salivary flow in young adults with good oral health. The study also examined whether anthropometric measurements and gender could influence the variables studied. A total of 171 subjects were selected (125 females, 46 males). Masticatory performance was evaluated with the sieve method, and perceived masticatory ability was measured using the visual analogue scale. Taste was evaluated using the drop test with four different flavors in three different concentrations, and unstimulated and stimulated saliva flows were measured. The anthropometric variables measured included body mass index (BMI) and waist circumference (WC). The independent variables studied could not predict masticatory performance. The independent variables, BMI, WC, and gender, predicted 14% of perceived masticatory ability, and BMI predicted 5% of taste. Masticatory performance was not related to salivary flow or anthropometric parameters in young healthy adults. Perceived masticatory ability was related to BMI, WC, and gender, whereas taste was only weakly related to BMI. The flow rate did not exhibit a statistically significant difference between males and females for the anthropometric groups. (J Oral Sci 58, 391-399, 2016). PMID- 27665980 TI - Scanning electron microscopy with energy dispersive X-ray spectrophotometry analysis of reciprocating and continuous rotary nickel-titanium instruments following root canal retreatment. AB - This study aimed to evaluate superficial defects and the composition of Reciproc R25 and ProTaper Retreatment file systems (Dentsply Maillefer, Ballaigues, Switzerland) used for retreatment. A total of 100 maxillary incisor teeth were randomly divided into the following two groups: Reciproc R25 (n = 25) and ProTaper Retreatment instrument (n = 75) groups. The nickel-titanium (Ni-Ti) compositions of the files before and after use were analyzed using energy dispersive X-ray spectrophotometry (EDX). Chi-square, Mann-Whitney U, and Kruskal Wallis tests were used to analyze the data. ProTaper Retreatment instrument group showed a significantly higher number of defects than the Reciproc group (P < 0.05). No instrument fracture was detected. The presence of debris was observed in both groups before use, although the level was significantly higher in the ProTaper Retreatment group, which consisted of metals (P < 0.05). There was no significant difference between new and used instruments with regard to Ni-Ti composition (P < 0.05). EDX analysis showed that both the Reciproc and ProTaper Retreatment instruments had a Ni-Ti composition that was within the standards specified by the American Society of Testing and Materials. This study confirmed the use of both the Reciproc R25 file and ProTaper Retreatment file system for root canal filling removal in straight root canals as a safe procedure. (J Oral Sci 58, 401-406, 2016). PMID- 27665981 TI - Expression of Wilms' tumor 1 (WT1) in ameloblastomas. AB - The Wilms' tumor 1 gene (WT1) was originally isolated and described as the gene responsible for Wilms' tumor. Although there is growing evidence linking the overexpression of WT1 to tumorigenesis, no reports on ameloblastoma are available at present. The aim of this study was to examine the expression of WT1 in various histological subtypes of ameloblastoma tissue specimens and in human ameloblastoma cell lines. Immunohistochemical analyses were performed on a total of 168 cases of ameloblastoma, one case of ameloblastic carcinoma, and five cases of tooth germs (control). Three immortalized human dental epithelial cell lines (HAM1, HAM2, and HAM3) derived from the same ameloblastoma patient were used for reverse transcription-polymerase chain reaction (RT-PCR) and western blot assays. The tooth germs did not express WT1 (0%), and more than half of the ameloblastoma cases showed WT1 overexpression (54.7%). Immunoreactivity of solid-type ameloblastoma (76.1%) was more evident than that of unicystic-type ameloblastoma (40.9%). The expression level of WT1 mRNA in HAM2 was higher than that in HAM1 (moderate) and HAM3 (weak), showing the heterogeneity of tumor cells. The WT1 protein was strongly detected in HAM2 and minimally detected in HAM1 and HAM3. Our results suggest that WT1 expression influences the pathogenesis of ameloblastoma by varying its expression level in different histological types. (J Oral Sci 58, 407-413, 2016). PMID- 27665982 TI - Effect of low-intensity pulsed ultrasound (LIPUS) on mandibular condyle growth in rats analyzed with micro-CT. AB - This study examined the effects of a bite-jumping appliance combined with low intensity pulsed ultrasound (LIPUS) stimulation on the mandibular condyle of growing rats using micro CT (mCT) and histological examinations. Twelve Wistar rats were divided into three groups of four individuals each: Group 1 was an untreated control group, Group 2 received bite-jumping appliances, and Group 3 received bite-jumping appliances and LIPUS stimulation (15 min/day, 2 weeks) to the temporomandibular region. We measured the length and three-dimensional bone volume of each rat's mandibular condyle using mCT. The condylar cartilage was observed after the rats had been sacrificed. There was no significant difference in condylar sagittal width among the groups. The bite-jumping appliance combined with LIPUS stimulation increased the condylar major axis, mandibular sagittal length and condylar bone volume to a greater degree than use of the bite-jumping appliance alone. Histological examination demonstrated hypertrophy of the condylar cartilage layers, the fibrous layer and hypertrophic cell layer of the rats treated with bite-jumping appliances combined with LIPUS stimulation in comparison to rats treated with bite-jumping appliances alone. (J Oral Sci 58, 415-422, 2016). PMID- 27665983 TI - Lipid profile and high-sensitivity C-reactive protein levels in obese and non obese subjects undergoing non-surgical periodontal therapy. AB - Periodontal treatment may improve the metabolic control of dyslipidemia. The aim of this study was to evaluate the lipid profile and high-sensitivity C-reactive protein (hs-CRP) levels in obese and non-obese patients undergoing periodontal therapy. Patients with generalized chronic periodontitis were divided into obese (n = 28) and non-obese groups (n = 26). The periodontal parameters (visible plaque index, gingival bleeding index, probing depth, clinical attachment level, and bleeding on probing), anthropometric measurements (body mass index, waist circumference, and body fat), and serum analyses (triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, fasting glucose, glycated hemoglobin, and hs-CRP) were measured at baseline and 90 days after periodontal treatment. The results showed that the obese subjects presented alterations in triglycerides, total cholesterol, low-density lipoprotein, and hs CRP at baseline when compared with non-obese patients (P < 0.05). Periodontal treatment could improve the periodontal parameters in both groups similarly (P > 0.05). Obese subjects showed a significant decrease in the levels of triglycerides, total cholesterol, low-density lipoprotein, and hs-CRP post therapy (P < 0.05), while non-obese patients showed improvement only in hs-CRP (P < 0.05). In conclusion, periodontal treatment could improve the periodontal parameters and circulating hs-CRP in obese and non-obese subjects. Lipid profile was modified only in obese patients post-therapy. (J Oral Sci 58, 423-430, 2016). PMID- 27665984 TI - Effectiveness of disinfectants on the adherence of Candida albicans to denture base resins with different surface textures. AB - The aim of the present study was to compare the effects of some disinfectants, including ethanol extract of propolis (EEP), on the adhesion of Candida albicans to denture base resins. Seventy-two acrylic resin samples were prepared, half of which was polished and the other half was roughened. C. albicans strain ATCC 10231 was incubated on Sabouraud dextrose agar (SDA) at 37 degrees C for 48 h. The adhesion period was completed by keeping the cells in this suspension for 90 min at 37 degrees C. Specimens were then immersed in the following solutions: 1%, 2%, and 5% sodium hypochlorite; 4% chlorhexidine gluconate; and 10% EEP. Quantification of the antifungal activity of the chemical solutions was performed using the colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay test. One-way ANOVA and post-hoc Tukey tests were performed to evaluate the effectiveness of chemical agents. Polished and roughened surfaces were compared using independent sample t-test. The mean surface roughness value was 0.35 (+/-0.04) um for the polished group and 1.2 (+/-0.2) um for the roughened group. The contact angles of both surfaces showed statistically significant difference, and 10% EEP solution exhibited significantly less removal of adherent viable C. albicans cells in both groups. All forms of sodium hypochlorite solutions yielded higher efficiency than 4% chlorhexidine gluconate and EEP solutions (P < 0.05). (J Oral Sci 58, 431-437, 2016). PMID- 27665985 TI - Prenatal alcohol exposure reduces mandibular calcium and phosphorus concentrations in newborn rats. AB - Previous studies suggest that prenatal alcohol exposure affects fetal bone development, including bone quality. This study evaluated the chemical composition of mandibles from newborn rats after maternal 20% alcohol consumption before and throughout gestation. Nine rats were initially distributed into three groups: an Alcohol group, Pair-fed group, and Control group. The groups were fed prespecified diets for 8 weeks before and the 3 weeks during pregnancy. At age 5 days, eight newborns from each group were euthanized (total, n = 24). Using energy dispersive spectrometry, we evaluated samples of mandibles from newborns to identify changes in bone mineralization, specifically Ca and P concentrations. Ca and P concentrations were lower in the Alcohol group than in the Control and Pair-fed groups (P = 0.003 and P = 0.001, respectively). In summary, alcohol exposure before and throughout gestation reduces mandibular Ca and P concentrations in newborn rats. (J Oral Sci 58, 439-444, 2016). PMID- 27665986 TI - Oral leukoplakia associated with amalgam restorations. AB - The World Health Organization has defined oral leukoplakia (OL) as "a white patch or plaque of the oral mucosa that cannot be characterized clinically or pathologically as any other disease". A 21-year-old male with OL presented with a bilateral burning sensation in the buccal mucosa. The patient had amalgam restorations, and an epicutaneous patch test indicated a positive response to amalgam. The amalgam restorations were therefore removed and the cavities were refilled with a composite resin restorative material. During 5 years of follow up, there was no recurrence of the oral lesions. This case illustrates that amalgam fillings may cause OL lesions. (J Oral Sci 58, 445-448, 2016). PMID- 27665987 TI - Physiological and biochemical responses of sunflower (Helianthus annuus L.) exposed to nano-CeO2 and excess boron: Modulation of boron phytotoxicity. AB - Little is known about the interaction of nanoparticles (NPs) with soil constituents and their effects in plants. Boron (B), an essential micronutrient that reduces crop production at both deficiency and excess, has not been investigated with respect to its interaction with cerium oxide NPs (nano-CeO2). Considering conflicting results on the nano-CeO2 toxicity and protective role as antioxidant, their possible modulation on B toxicity in sunflower (Helianthus annuus L.) was investigated. Sunflower was cultivated for 30 days in garden pots containing original or B-spiked soil amended with nano-CeO2 at 0-800 mg kg-1. At harvest, Ce and B concentrations in tissues, biomass, and activities of stress enzymes in leaves were determined. Results showed that in the original soil, Ce accumulated mainly in roots, with little translocation to stems and leaves, while reduced root Ce was observed in plants from B-spiked soil. In the original soil, higher levels of nano-CeO2 reduced plant B concentration. Although morphological effects were not visible, changes in biomass and oxidative stress response were observed. Sunflower leaves from B-spiked soil showed visible symptoms of B toxicity, such as necrosis and chlorosis in old leaves, as well as an increase of superoxide dismutase (SOD) activity. However, at high nano-CeO2 level, SOD activity decreased reaching values similar to that of the control. This study has shown that nano-CeO2 reduced both the B nutritional status of sunflower in original soil and the B phytotoxicity in B-spiked soil. PMID- 27665988 TI - Effective and efficient prevention of HIV infection. PMID- 27665989 TI - Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study. AB - BACKGROUND: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation. METHODS: We developed a deterministic mathematical model, calibrated to the well defined Dutch HIV epidemic among MSM, to predict the effect and cost effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below ?20 000 were considered to be cost-effective in this analysis. FINDINGS: Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as ?11 000 (IQR 9400-14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as ?2000 (IQR 1300-3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on demand PrEP can be considered cost-saving if the price is reduced by 30-40%. INTERPRETATION: PrEP for HIV prevention among MSM in the Netherlands is cost effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving. FUNDING: None. PMID- 27665990 TI - New perspectives to the enterotoxigenic E. coli F4 porcine infection model: Susceptibility genotypes in relation to performance, diarrhoea and bacterial shedding. AB - Enterotoxigenic E. coli (ETEC), causing post-weaning diarrhoea, is a major problem in weaned piglets. Individual animal responses to ETEC infection show high variability in animal experiments. Two studies were designed to optimize the ETEC F4ac infection model in piglets by combining the genotype susceptibility with performance, diarrhoea incidence and bacterial shedding. The studies were performed with respectively 120 and 80 male piglets that were tested for susceptibility or resistance towards ETEC O149:F4ac by a DNA marker based test. Three different genotypes were observed; resistant (RR), susceptible heterozygote (RS) and susceptible homozygote (SS). Piglets, were orally infected with an inoculum suspension (containing 1.5E8 CFU/ml ETEC F4ac) at day 0, 1 and 2 of the study. Performance, diarrhoea incidence and bacterial shedding were followed for 21days. In the first week after challenge a difference in average daily gain was observed between resistant and susceptible piglets in both studies. For the complete study period no significant differences were observed. Diarrhoea incidence was significantly higher in susceptible pigs compared to the resistant pigs in the first week after challenge. Bacterial shedding was much higher in the susceptible pigs and ETEC excretion lasted longer. ETEC was hardly detected in the faecal material of the resistant pigs. In conclusion, susceptible pigs showed higher diarrhoea incidence and higher numbers of faecal ETEC shedding in the first week after challenge compared to resistant pigs. The DNA marker based test can be used to select pigs that are susceptible for ETEC for inclusion in ETEC infection model, resulting in less animals needed to perform infection studies. PMID- 27665992 TI - Commentary on 'Endovascular Stent Graft Repair is an Effective and Safe Alternative Therapy for Arteriovenous Graft Pseudoaneurysms'. PMID- 27665991 TI - Patient Specific Wall Stress Analysis and Mechanical Characterization of Abdominal Aortic Aneurysms Using 4D Ultrasound. AB - OBJECTIVES: The aim of this study was to perform wall stress analysis (WSA) using 4D ultrasound (US) in 40 patients with an abdominal aortic aneurysm (AAA). The geometries and wall stress results were compared with computed tomography (CT) in seven patients. Additionally, the WSA models were calibrated using 4D motion estimation, resulting in patient specific material parameters that were compared among patients. METHODS: 4D-US images were acquired for 40 patients (AAA diameter 27-52 mm). Patient specific AAA geometries and wall motion were extracted from the 4D-US. WSA was performed and corresponding patient specific material properties were derived. For seven patients, CT data were available and analyzed for geometry and wall stress comparison. RESULTS: The 4D-US based 99th percentile wall stress ranged from 198 to 390 kPa. Regression analysis showed no significant relation between wall stress and diameter of the AAA. The similarity indices between US and CT were very good and ranged between 0.90 and 0.96, and the 25th, 50th, 75th, and 95th percentile wall stresses of the US and CT data were in agreement. The characterized patient specific shear modulus had a median of 1.1 MPa (interquartile range, 0.7-1.4 MPa). Based on the maximum AAA diameter, the AAAs were divided in a small, medium, and large diameter groups. The largest AAAs revealed an increased wall stiffness compared with the smallest AAAs. CONCLUSIONS: 4D ultrasound is applicable for wall stress analysis of AAAs, and offers the opportunity to perform wall stress analysis over time, also for AAAs who do not qualify for a CT or magnetic resonance imaging. Moreover, the patient specific material properties can be determined, which could possibly improve risk assessment. PMID- 27665993 TI - The modulating effects of propofol and its lipid carrier on canine neutrophil functions. AB - Propofol (2,6-diisopropylphenol), being used as an intravenous sedative and anesthetic agent, influences not only upon nervous system but also for host inflammatory response through modulating neutrophil functions. This study is designed to evaluate the modulating effects of propofol and its lipid carrier administration at clinically relevant rate on canine neutrophil functions. Clinically healthy beagle dogs were received propofol (8.8 mg/kg) from cephalic vein and maintained with propofol dropping infusion (26.4 mg/kg/hr). Blood samples were collected from the dogs before infusion and 30 min after the start of propofol administration, and neutrophil functions were evaluated. The dogs were also administered lipid carrier, and neutrophil functions were evaluated in the same manner as propofol administration. Peripheral white blood cell and neutrophil counts decreased after the propofol or lipid carrier administration. The administration of propofol or lipid carrier significantly reduced neutrophil adherence ability. The superoxide production of neutrophils was measured by luminol-dependent chemiluminescence response using with opsonized zymosan. Peak height of neutrophil chemiluminescence curve was reduced by propofol and lipid carrier administration, on the contrary, peak time of neutrophil chemiluminescence curve was delayed. Administration of propofol or lipid carrier also reduced neutrophil adherence ability to nylon fibers. In the present study, we showed the modulating effects of propofol and its lipid carrier on canine neutrophil functions. However, there was no significant difference in the modulating effects between propofol group and lipid carrier group. Therefore, the modulating effects observed here were deeply concerned in lipid carrier administration. PMID- 27665994 TI - Regulation of type 2 diabetes by helminth-induced Th2 immune response. AB - Helminth-induced type 2 cytokines increase the number of regulatory T cells and alternatively activated macrophages, resulting in modulation of the host-immune system. Studies on these parasite-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes (T2D). Previous studies have suggested that progression of obesity-associated metabolic abnormalities is under pathophysiological control of CD4+ T cells. Glucose absorption through the intestinal epithelium reduced after infection in a STAT-6-dependent manner. In this study, we investigated whether infection with the gastrointestinal nematode parasite Heligmosomoides polygyrus (Hp) can modulate T2D-associated pathology in a mouse model (KK Ay/TaJcl). KK-Ay/TaJcl mice were inoculated with infective third-stage Hp larvae and studied at Day 8 following infection. Uninfected KK-Ay/TaJcl mice showed high blood glucose levels even 120 min after administration of glucose by IP injection. However, it was significantly improved in the infected group. HOMA-IR, fat accumulation and FAS gene expression in the liver were significantly decreased by Hp infection. GLUT2 gene expression in this group was significantly lower than that in the uninfected diabetic mice, which might be related to the decrease in glucose absorption in the parasite-infected intestine. In conclusion, helminth-induced type 2 immune responses might contribute to T2D disease control. PMID- 27665995 TI - Role of invariant NKT cells in lipopolysaccharide-induced lethal shock during encephalomyocarditis virus infection. AB - Viral infections can give rise to secondary bacterial infections. In the present study, we examined the role of invariant natural killer T (iNKT) cells in lipopolysaccharide (LPS)-induced lethal shock during encephalomyocarditis virus (EMCV) infection. Wild-type (WT) mice and Jalpha18 gene knockout (Jalpha18 KO) mice were inoculated with EMCV, 5days prior to challenging with LPS. The survival rate of Jalpha18 KO mice subjected to EMCV and LPS was significantly higher than that of WT mice. TNF-alpha and nitric oxide (NO) production were increased in WT mice, than that in Jalpha18 KO mice, after the administration of EMCV and LPS. EMCV infection increased the number of iNKT cells and IFN-gamma production by iNKT cells in WT mice. Moreover, EMCV infection enhanced the expression of Toll like receptor 4 (TLR4) in the lung and spleen. IFN-gamma also increased the expression of TLR4 in splenocytes. These findings indicated that EMCV infection activated iNKT cells, and IFN-gamma secreted from the iNKT cells up-regulated the expression of TLR4 in various tissues. As a result, EMCV-infected mice were susceptible to LPS and easily developed the lethal shock. In conclusion, iNKT cells were involved in the development of LPS-induced lethal shock during EMCV infection. PMID- 27665996 TI - IFN-gamma-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection: Paradoxical post-transplantation effects of IFN-gamma. AB - PURPOSE: IFN-gamma is a protypical proinflammatory cytokine that plays a central role in inflammation and acute graft rejection. Accumulating evidence indicates that IFN-gamma can exert previously unexpected immunoregulatory activities. However, little is known about the role of IFN-gamma secreted by Th1-like regulatory T cells in human kidney transplantation. METHODS: To determine the function of IFN-gamma in acute T cell-mediated renal allograft rejection (ACR), we examined serum cytokine expression profiles in ACR patients by human cytokine multiplex immunoassay and analyzed the cellular origins of IFN-gamma in peripheral blood and renal allograft biopsies from ACR cases and controls by flow cytometry and immunohistochemistry, respectively. RESULTS: The results showed significant reduction in serum concentrations of Th1-inducing cytokines IL-12p70 and IFN-gamma as well as Th2-related cytokine IL-4 in ACR patients compared with stable controls. However, levels of several Th1-, Th2- and Th17-related cytokines, such as IL-2, TNF-alpha, TNF-beta, IL-12 (p40), IL-10, IL-15, IL-17, IL-21, and IL-23, as well as the frequencies of Th1 and Th17 cell, did not differ between ACR cases and stable controls. Moreover, we found the levels of IFN-gamma were correlated with those of the anti-inflammatory factor, IL-1 receptor antagonist (IL-1Ra) in ACR. Notably, the Th1-like Treg cell-to-Foxp3- Th1 cell ratio was significantly lower in ACR patients compared with that in stable controls. In graft biopsies from ACR patients, Treg cells and Th1-like Treg cells were less abundant than those without ACR. CONCLUSIONS: Our study indicates that IFN-gamma secreted from Th1-like Treg cells negatively modulates ACR. PMID- 27665998 TI - Thioredoxin and redox signaling: Roles of the thioredoxin system in control of cell fate. AB - Reactive oxygen species (ROS) are not only cytotoxic products from external and internal environment, but also important mediators of redox signaling. Therefore, thioredoxin (Trx) as an antioxidant maintains the balance of the thiol-related redox status, and also plays pivotal roles in the regulation of redox signaling. Trx senses and responds to environmental oxidative stress and ROS generated by cellular respiration, metabolism, and immune response, and then modulates the redox status, function, and activity of its target signaling proteins. Dysregulation of such the Trx system affects various cellular functions and cell fate such as survival and cell death, leading to human diseases including cancer and inflammation. This review focuses on Trx and its target proteins involved in redox signaling, which are critical for the control of cell fate such as cell survival and apoptosis, and addresses how Trx regulates those effector proteins and redox signaling. PMID- 27665997 TI - Agitation, Delirium, and Cognitive Outcomes in Intracerebral Hemorrhage. AB - BACKGROUND: Delirium predicts higher long-term cognitive morbidity. We previously identified a cohort of patients with spontaneous intracerebral hemorrhage and delirium and found worse outcomes in health-related quality of life (HRQoL) in the domain of cognitive function. OBJECTIVE: We tested the hypothesis that agitation would have additional prognostic significance on later cognitive function HRQoL. METHODS: Prospective identification of 174 patients with acute intracerebral hemorrhage, measuring stroke severity, agitation, and delirium, with a standardized protocol and measures. HRQoL was assessed using the Neuro-QOL at 28 days, 3 months, and 1 year. Functional outcomes were measured with the modified Rankin Scale. RESULTS: Among the 81 patients with HRQoL follow-up data available, patients who had agitation and delirium had worse cognitive function HRQoL scores at 28 days (T scores for delirium with agitation 20.9 +/- 7.3, delirium without agitation 30.4 +/- 16.5, agitation without delirium 36.6 +/- 17.5, and neither agitated nor delirious 40.3 +/- 15.9; p = 0.03) and at 1 year (p = 0.006). The effect persisted in mixed models after correction for severity of neurologic injury, age, and time of assessment (p = 0.0006) and was not associated with medication use, seizures, or infection. CONCLUSIONS: The presence of agitation with delirium in patients with intracerebral hemorrhage may predict higher risk of unfavorable cognitive outcomes up to 1 year later. PMID- 27665999 TI - Inhibition of aldo-keto reductase family 1 member B10 by unsaturated fatty acids. AB - A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, is a cytosolic NADPH-dependent reductase toward various carbonyl compounds including reactive aldehydes, and is normally expressed in intestines. The enzyme is overexpressed in several extraintestinal cancers, and suggested as a potential target for cancer treatment. We found that saturated and cis-unsaturated fatty acids inhibit AKR1B10. Among the saturated fatty acids, myristic acid was the most potent, showing the IC50 value of 4.2 MUM cis-Unsaturated fatty acids inhibited AKR1B10 more potently, and linoleic, arachidonic, and docosahexaenoic acids showed the lowest IC50 values of 1.1 MUM. The inhibition by these fatty acids was reversible and kinetically competitive with respect to the substrate, showing the Ki values of 0.24-1.1 MUM. These fatty acids, except for alpha linoleic acid, were much less inhibitory to structurally similar aldose reductase. Site-directed mutagenesis study suggested that the fatty acids interact with several active site residues of AKR1B10, of which Gln114, Val301 and Gln303 are responsible for the inhibitory selectivity. Linoleic and arachidonic acids also effectively inhibited AKR1B10-mediated 4-oxo-2-nonenal metabolism in HCT-15 cells. Thus, the cis-unsaturated fatty acids may be used as an adjuvant therapy for treatment of cancers that up-regulate AKR1B10. PMID- 27666000 TI - Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF kappaB and suppressing CCR7/CCL19/CCL21. AB - Baicalin, extracted and purified from the Chinese medicinal plant, Scutellaria baicalensis Georgi (Huang qin in Chinese), exhibits potent anti-inflammatory activity against asthma. However, it remains unknown whether baicalin inhibits the activity of CC chemokine receptor 7 (CCR7) and its ligands, which are crucial for the initiation of airway inflammation. In the present study, we investigated the effects of baicalin on CCR7 and its ligands, CCL19 and CCL21, as well as on the nuclear factor-kappaB (NF-kappaB) pathway in a mouse model of asthma. A mouse model of acute asthma was established by exposing the mice to ovalbumin (OVA) (by intraperitoneal injection and inhalational challenge). Within 24 h of the final OVA challenge, lung function was detected by direct airway resistance analysis. Lung tissues were examined for pathological changes. Inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were assessed. ELISA was utilized to evaluate the OVA-IgE, CCL19 and CCL21 levels in BALF. The interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels in serum were also detected by ELISA. The protein expression levels of CCR7, as well as that of phosphorylated IkappaBalpha (p-IkappaBalpha) and phosphorylated p65 (p-p65) were determined by western blot analysis and RT-qPCR was used to determine the CCR7 mRNA levels. Our data demonstrated that the oral administration of baicalin significantly improved pulmonary function and attenuated inflammatory cell infiltration into the lungs. Baicalin also decreased the levels of OVA-IgE, IL-6, TNF-alpha and CCR7, as well as those of its ligand, CCL19; the levels of NF-kappaB were also markedly suppressed by baicalin. The CCR7 mRNA level was substantially decreased. Our results thus suggest that baicalin exerts an inhibitory effect on airway inflammation, and this effect may be associated with the inhibition of CCR7 and CCL19/CCL21, which may provide new mechanistic insight into the anti-inflammatory effects of baicalin. PMID- 27666001 TI - Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice. AB - Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine. After 40 days of binge-eating for 2 h, three days a week (PND 29-69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice. Circulating leptin and ghrelin levels and the effects of bingeing on fat on CB1 mu opioid receptor (MOr) and ghrelin receptor (GHSR) gene expression in the Nucleus Accumbens (NAcc) and Ventral Tegmental Area (VTA) were also assessed. Our results showed a significant escalation in the consumption of a high-fat diet between the first and last week. High-fat binge (HFB) animals were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the paradigms assayed, and animals under fat withdrawal were more vulnerable to the reinstatement of conditioned place preference. HFB mice also showed enhanced cocaine self-administration. After fat withdrawal, exposure to a new fat binge reinstated cocaine seeking. Although HFB did not modify leptin levels, a decrease in plasmatic ghrelin was observed. Moreover, this pattern of fatty diet resulted in a reduction of MOr and CB1 gene expression in the NAcc and an increase in GHSR expression in the VTA. We propose that bingeing on fat during adolescence induces long-lasting changes in the brain through the sensitization of brain reward circuits, which predisposes individuals to seek cocaine during adulthood. PMID- 27666002 TI - Pre-hospital ticagrelor in patients with ST-segment elevation myocardial infarction with long transport time to primary PCI facility. AB - BACKGROUND: Pre-hospital ticagrelor, given less than 1h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion. METHODS: We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 (ClinicalTrials.gov id: NCT01347580). The median time from ticagrelor administration and PCI was 2.08h (95% CI 1.66-2.84) in the Pre-treatment Group and 0.56h (95% CI 0.33-0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint. RESULTS: The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88+/-1.14 vs 0.53+/ 0.86, P=0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups. CONCLUSIONS: In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI. PMID- 27666003 TI - Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity. AB - Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxo-induced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability. Here we investigated the effect of Doxo 1uM for 24h of stimulation on cultured neonatal rat cardiomyocytes. We showed that Doxo inhibits basal autophagy. This inhibition is due to both Akt/mTOR signaling pathway activation and Beclin 1 level decrease. To assess the role of autophagy on Doxo-induced cardiomyocyte death, we evaluated the effects 3-methyladenine (3-MA), bafilomycin A1 (BafA), siRNA Beclin 1 (siBeclin 1) and rapamycin (Rapa) on cell viability. Inhibition of autophagy with 3-MA, BafA and siBeclin 1 increased lactate dehydrogenase (LDH) release but, when autophagy was induced by Rapa, Doxo-induced cardiomyocyte death was decreased. These results suggest that Doxo inhibits basal autophagy and contributes to cardiomyocyte death. Activation of autophagy could be used as a strategy to protect the heart against Doxo toxicity. PMID- 27666004 TI - The 10-year trend of adult diabetes, prediabetes and associated risk factors in Tehran: Phases 1 and 4 of Tehran Lipid and Glucose Study. AB - BACKGROUND: Type 2 diabetes is a global problem with significant morbidity and healthcare costs. In this study, we aimed to determine the 10-year trend of diabetes, prediabetes and their risk factors in the adult urban population of Tehran Lipid and Glucose Study (TLGS). MATERIALS AND METHODS: In this cross sectional study, we included all patients above 20 years of age who were registered in phases 1 and 4 of TLGS. Each phase had a 3-year duration. 4580 patients were recruited in each phase (916 patients in each age-group, including 3772 males and 5145 females). Random cluster sampling was used in phase 1 and convenience sampling was used in phase 4. Diabetes and glucose tolerance status were determined according to the 1991 criteria of the American Diabetes Association. In our five age groups, risk factors were compared, which included physical activity, waist circumference, body mass index, education, smoking, lipid profile and family history. Exclusion criteria were placement of an individual in the same age-group in the two phases and pregnancy. We calculated the prevalence of diabetes and dysglycemia in each age-group. Age-specific prevalence rates were determined. Prevalence of risk factors in the two phases were compared using chi-square test and Student t-test. Mann-Whitney U test was used to analyze the variables with non-normal distribution. RESULTS: In this study, 3976 individuals were recruited in phase 1 (2308 women and 1668 men; female to male ratio 1.38) and 4941 individuals were recruited in phase 4 (2837 women and 2104 men; female to male ratio 1.35). Prevalence of prediabetes in all age groups (except for the 30-39 years age-group) were increased in phase 4 compared to phase 1. Prevalence of known diabetes in all age groups were increased in phase 4 compared to phase 1, yet, the increase was significant only in the 30-39 and 60-69 years age groups (1.8% vs. 0.7% and 19.0% vs. 10.2%, respectively). Newly diagnosed diabetes was decreased in all age groups in phase 4, except for the 60-69 years age-group. The incidence of newly diagnosed diabetes in the 60-69 years age-group was significantly higher in phase 4 compared to the similar age-group of phase 1 (15.2% vs. 11.8%; p<0.001). Physical activity, body mass index, waist circumference (central obesity), general obesity, smoking (except for the 30-39 and 40-49 years age groups), and level of education were significantly higher in phase 4 compared to phase 1. Marriage rates were significantly lower in phase 4 compared to phase 1 across all studied age groups. CONCLUSION: We observed an increasing trend in the prevalence of diabetes over a 10-year period in TLGS. This is an accordance with estimates in this field and highlights the need for education, prevention, treatment and control of diabetes. We also found increased rates of central and general obesity, smoking and divorce along with decreased marriage rates, which should be considered by the healthcare policymakers and state health officials as significant risk factors of diabetes. PMID- 27666005 TI - Preparation before acid etching in fissure sealant therapy: yes or no?: A systematic review and meta-analysis. AB - BACKGROUND: The authors of this systematic review and meta-analysis had 2 aims: to evaluate fissure sealant retention with and without the use of a preparation method and to compare fissure sealant retention using the preparation-only method before sealant placement with the conventional acid-etching procedure. TYPES OF STUDIES REVIEWED: The authors conducted a literature search (from database inception through June 2, 2016) to identify studies for inclusion in this systematic review. The authors assessed the quality of the evidence with the modified Jadad scale and performed the meta-analysis by using a random-effects model. RESULTS: The authors considered 12 studies (8 for the first part and 4 for the second part) that met the inclusion criteria for the systematic review and meta-analysis. In the analysis of the first part of the systematic review, the authors found that the preparation method before acid etching had a significant positive effect on fissure sealant retention (odds ratio, 3.262; 95% confidence interval, 1.782-5.971; P = .001). In the analysis of the second part of the systematic review, the authors found that there were no significant differences between the preparation-only method and the conventional acid-etching method in terms of fissure sealant retention (odds ratio, 1.241; 95% confidence interval, 0.534-2.888; P = .616). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The use of a preparation method before fissure sealant application can increase sealant retention. However, preparation alone cannot substitute the conventional acid etching method before sealant placement. PMID- 27666006 TI - Predictors for bowel resection and the presence of a pathological lead point for operated childhood intussusception: A multi-center study. AB - BACKGROUND: Intussusception may require bowel resection. Here, we aim to define factors that predict the need of bowel resection and the presence of pathological lead point. METHODS: A retrospective review was taken from three tertiary centers for all operated intussusception patients from January 2010 to December 2014. Patient demographics were recorded. Statistical analysis was performed, and risk factors were derived by binary logistic regression. RESULTS: Five thousand ninety six patients were treated for intussusception with 73 (57 male, 16 female) operated. The median age was 23.2months, and median duration of symptoms was 2days. Twenty-eight patients (38.4%) required bowel resection. Logistic regression demonstrated that older age (p=0.018) and longer duration of symptoms (p=0.009) were associated with bowel resection. Furthermore, older age was a predictive factor for the presence of a pathological lead point (p=0.01). A palpable abdominal mass was also found to be associated with the need of bowel resection (risk ratio 2.3) and the presence of pathological lead point (risk ratio 2.3) independently. CONCLUSION: Older age at presentation and a longer duration of symptoms are positive predictors for the need of bowel resection in intussusception. The presence of a pathological lead point is more likely in older children. LEVEL OF EVIDENCE: Case series with no comparison group - Level IV. PMID- 27666007 TI - More than one-third of successfully nonoperatively treated patients with complicated appendicitis experienced recurrent appendicitis: Is interval appendectomy necessary? AB - BACKGROUND: Although nonoperative treatment (non-OPT) for complicated appendicitis is performed widely, the long-term outcomes and merits of interval appendectomy (IA) need to be evaluated. METHODS: Between April 2007 and December 2013, all appendicitis patients with well-circumscribed abscess or phlegmon were required to select either laparoscopic surgery (OPT) or non-OPT with optional IA on admission. Optional IA was planned at >=3months after non-OPT. For non-OPT, intravenous injection of antibiotics was continued until the serum C-reactive protein concentration decreased to <0.5mg/dL, with occasional drainage of abscesses. RESULTS: Thirty-three patients chose OPT, and 55 chose non-OPT. Among non-OPT patients, 16 selected IA. The success rate of non-OPT was 98.2%. Recurrence occurred in 13 (34.2%) of the 38 non-IA group patients. Although the non-IA group patients frequently had perforated appendicitis at recurrence, they visited the hospital earlier than at the initial appendicitis and had less inflammation. Readmission rate or complications in patients undergoing IA were not different compared with those of the patients in the non-IA group, who had recurrence at >=3months, or with those of patients in the OPT group. CONCLUSION: Although many patients experienced recurrent appendicitis after successful nonoperative treatment, IA may not be necessary after non-OPT. LEVEL OF EVIDENCE: Prospective comparative study, level II. PMID- 27666008 TI - Same day discharge protocol implementation trends in laparoscopic cholecystectomy in pediatric patients. AB - PURPOSE: After investigating barriers for same day discharge (SDD) after laparoscopic cholecystectomy (LC), we employed a protocol which we have followed with a prospective, observational study. METHODS: A single institution, prospective observational study was performed from July 2014 to 2015 (2nd period). These data were compared to our initial experience with an SDD protocol from January 2013 to July 2014 (1st period). RESULTS: A total of 191 LCs were analyzed, 116 in the 1st period and 75 in the second period. In the 1st period, 47% were discharged the same day compared to 78% in the 2nd period (P<0.001). There was no difference in postoperative complications or readmissions between those discharged and those who spent the night. Additionally, there was no difference between admitted and SDD patients in age, BMI, or gender. Reasons for admission included pain (12%) and emesis (12%), and 1 patient had a syncopal event. However, the majority stayed with no identifiable patient factor. CONCLUSION: SDD after LC is safe and effective and implementing and revising a standardized clinical protocol can substantially improve the success of SDD. LEVEL OF EVIDENCE: Retrospective comparative study, level III. PMID- 27666009 TI - Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury. AB - Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. PMID- 27666010 TI - A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells. AB - The generation of distinct hematopoietic cell types, including tissue-resident immune cells, distinguishes fetal from adult hematopoiesis. However, the mechanisms underlying differential cell production to generate a layered immune system during hematopoietic development are unclear. Using an irreversible lineage-tracing model, we identify a definitive hematopoietic stem cell (HSC) that supports long-term multilineage reconstitution upon transplantation into adult recipients but does not persist into adulthood in situ. These HSCs are fully multipotent, yet they display both higher lymphoid cell production and greater capacity to generate innate-like B and T lymphocytes as compared to coexisting fetal HSCs and adult HSCs. Thus, these developmentally restricted HSCs (drHSCs) define the origin and generation of early lymphoid cells that play essential roles in establishing self-recognition and tolerance, with important implications for understanding autoimmune disease, allergy, and rejection of transplanted organs. PMID- 27666012 TI - Bone marrow stromal cells attenuate LPS-induced mouse acute liver injury via the prostaglandin E 2-dependent repression of the NLRP3 inflammasome in Kupffer cells. AB - The nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome participates in the pathogenesis of acute liver injury during sepsis. Bone marrow mesenchymal stem cells (BMSCs) attenuate sepsis through prostaglandin E 2 (PGE2) by increasing the interleukin-10 (IL-10) production of macrophages; moreover, NLRP3 inflammasome assembly is effectively regulated by IL 10 during infection. Whether BMSCs have an effect on the activation of the NLRP3 inflammasome and its underlying mechanism is unclear. Administering of BMSCs to mice or KCs after LPS stimulating have improved liver function and reduced activation of NLRP3 inflammasome in KCs. The beneficial effect of BMSCs was enhanced by over-expression of PGE2 and eliminated by silence of PGE2. Additionally, The IL-10 levels in the serum and supernatant were increased by given BMSCs and further increase by PGE2 over-expressed BMSCs, but decreased markedly by PGE2 silenced BMSCs. Furthermore, extracellular signal-regulated kinase 1 (ERK1) inhibitor reduced IL-10 production in KCs and blocked the inhibitory effect of PGE2 on the activation of the NLRP3 inflammasome. Our data reveal a novel mechanism of BMSC-mediated suppression of the activation of KCs through the secretion of PGE2 by BMSCs, which promotes KCs to secrete IL-10, leading to the inhibition of the NLRP3 inflammasome in KCs. PMID- 27666013 TI - Cell surface cathepsin G activity differs between human natural killer cell subsets. AB - Natural killer (NK) cells are critical in diverse defense mechanisms, including elimination of viral infected cells and destruction of tumor cells. NK cells are characterized by the ability to initiate apoptosis in target cells when their cell surface major histocompatibility complex class I (MHC I) repertoire is missing. On the other hand, NK cells are not activated when MHC I or non classical MHC molecules are found on the respective cells. It was demonstrated that cathepsin G (CatG) binds to the cell surface of NK cells; however, the distribution of this protease on the cell surface of NK cell subsets has not been identified. Here, we show that CatG cell surface level differs between NK cell subsets. CatG was determined on the protein- and activity level (activity-based probe MARS116) by using flow cytometry. Thus, MARS116 is a novel reporter of cell surface CatG activity and can be used to differentiate between distinct NK cell subsets. PMID- 27666011 TI - Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-leukemia. AB - Mesenchymal niche cells may drive tissue failure and malignant transformation in the hematopoietic system, but the underlying molecular mechanisms and relevance to human disease remain poorly defined. Here, we show that perturbation of mesenchymal cells in a mouse model of the pre-leukemic disorder Shwachman-Diamond syndrome (SDS) induces mitochondrial dysfunction, oxidative stress, and activation of DNA damage responses in hematopoietic stem and progenitor cells. Massive parallel RNA sequencing of highly purified mesenchymal cells in the SDS mouse model and a range of human pre-leukemic syndromes identified p53-S100A8/9 TLR inflammatory signaling as a common driving mechanism of genotoxic stress. Transcriptional activation of this signaling axis in the mesenchymal niche predicted leukemic evolution and progression-free survival in myelodysplastic syndrome (MDS), the principal leukemia predisposition syndrome. Collectively, our findings identify mesenchymal niche-induced genotoxic stress in heterotypic stem and progenitor cells through inflammatory signaling as a targetable determinant of disease outcome in human pre-leukemia. PMID- 27666014 TI - Xinqin exhibits the anti-allergic effect through the JAK2/STAT5 signaling pathway. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xinqin, a polyherbal medicine, is an important traditional Chinese herbal formula used in traditional oriental medicine for treatment of allergic rhinitis (AR). The formula is based on the Chinese Pharmacopoeia AIM OF THE STUDY: Previously, Xinqin exhibited potent anti-allergic effect in a guinea pig model of AR. In this study, we explored the molecular mechanism of the anti-allergic effect mediated by Xinqin. MATERIALS AND METHODS: AR was induced in guinea pigs (Hartley) with toluene-2, 4-diisocyanate (TDI) in vivo and in HMC-1 mast cells with A23187/phorbol 12-myristate-13-acetate (PMA) in vitro. The releases of allergic inflammatory mediators such as histamine, leukotriene (LT) D4, immunoglobulin (Ig) E, TNF-alpha, and IL-6 were analyzed for allergy. The mast cell degranulation was displayed in HMC-1 mast cells. The activities of janus protein kinase 2 (JAK2), signal transduction and activator of transcription 5 (STAT5) and suppressor of cytokine signaling 3 (SOCS3) were evaluated by Western blot. RESULTS: Treatment with Xinqin resulted in AR symptoms and decreases in levels of histamine, LTD4, IgE, TNF-alpha, and IL-6 in serum of guinea pig model of AR and in A23187/PMA-stimulated HMC-1 mast cells. Treatment with Xinqin also inhibited cell degranulation in A23187/PMA-stimulated HMC-1 mast cells. The JAK2/STAT5 signaling pathway could play an important role in the anti allergic activity mediated by Xinqin. CONCLUSIONS: Xinqin exerts the anti allergic effect by modulating mast cell-mediated allergic responses by down regulating JAK2/STAT5 signaling pathway. Results from this study provide a mechanistic basis for the application of Xinqin in the treatment of AR. PMID- 27666016 TI - Molecular basis for the formation of ribonucleoprotein complex of Crimean-Congo hemorrhagic fever virus. AB - Negative-sense single-strand RNA (-ssRNA) viruses comprise a large family of pathogens that cause severe human infectious diseases. All -ssRNA viruses encode a nucleocapsid protein (NP) to encapsidate the viral genome, which, together with polymerase, forms a ribonucleoprotein complex (RNP) that is packaged into virions and acts as the template for viral replication and transcription. In our previous work, we solved the monomeric structure of NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV), which belongs to the Nairovirus genus within the Bunyaviridae family, and revealed its unusual endonuclease activity. However, the mechanism of CCHFV RNP formation remains unclear, due to the difficulty in reconstructing the oligomeric CCHFV NP-RNA complex. Here, we identified and isolated the oligomeric CCHFV NP-RNA complex that formed in expression cells. Sequencing of RNA extracted from the complex revealed sequence specificity and suggested a potential encapsidation signal facilitating the association between NP and viral genome. A cryo-EM reconstruction revealed the ring-shaped architecture of the CCHFV NP-RNA oligomer, thus defining the interaction between the head and stalk domains that results in NP multimerization. This structure also suggested a modified gating mechanism for viral genome encapsidation, in which both the head and stalk domains participate in RNA binding. This work provides insight into the distinct mechanism underlying CCHFV RNP formation compared to other -ssRNA viruses. PMID- 27666017 TI - Cardiac DPP-4 inhibition by saxagliptin ameliorates isoproterenol-induced myocardial remodeling and cardiac diastolic dysfunction in rats. AB - Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17.5 mg/kg via drinking water) for 2 weeks. In situ cardiac DPP-4 activity was measured by a colorimetric assay. Cardiac gene expressions were examined and an echocardiographic analysis was performed. Saxagliptin treatment significantly inhibited in situ cardiac DPP-4 activity and suppressed isoproterenol-induced myocardial remodeling and the expression of related genes without altering the blood glucose levels. Saxagliptin also significantly ameliorated cardiac diastolic dysfunction in isoproterenol-treated rats. In conclusion, the inhibition of DPP-4 activity in cardiac tissue by saxagliptin was associated with suppression of myocardial remodeling and cardiac diastolic dysfunction independently of its glucose lowering action in isoproterenol-treated rats. Cardiac DPP-4 activity may contribute to myocardial remodeling in the development of heart failure. PMID- 27666018 TI - Effect of naftopidil on brain noradrenaline-induced decrease in arginine vasopressin secretion in rats. AB - Naftopidil, an alpha1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP) plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA). NA (3 or 30 MUg/kg) was administered into the left ventricle (i.c.v.) of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.). Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.)-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.). Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats. PMID- 27666019 TI - Characterization of CD46 and beta1 integrin dynamics during sperm acrosome reaction. AB - The acrosome reaction (AR) is a process of membrane fusion and lytic enzyme release, which enables sperm to penetrate the egg surroundings. It is widely recognized that specific sperm proteins form an active network prior to fertilization, and their dynamic relocation is crucial for the sperm-egg fusion. The unique presence of the membrane cofactor protein CD46 in the sperm acrosomal membrane was shown, however, its behaviour and connection with other sperm proteins has not been explored further. Using super resolution microscopy, we demonstrated a dynamic CD46 reorganisation over the sperm head during the AR, and its interaction with transmembrane protein integrins, which was confirmed by proximity ligation assay. Furthermore, we propose their joint involvement in actin network rearrangement. Moreover, CD46 and beta1 integrins with subunit alpha3, but not alpha6, are localized into the apical acrosome and are expected to be involved in signal transduction pathways directing the acrosome stability and essential protein network rearrangements prior to gamete fusion. PMID- 27666020 TI - CD38 gene-modified dendritic cells inhibit murine asthma development by increasing IL-12 production and promoting Th1 cell differentiation. AB - Predominant T helper (Th)2 and impaired Th1 cell polarization has a crucial role in the development of asthma. Cluster of differentiation (CD)38 is associated with the increased release of interleukin (IL)-12 from dendritic cells (DCs) and DC-induced Th1 cell polarization. However, whether CD38 expression affects DC function in asthma development remains unknown. In the current study, adenoviruses were constructed containing the murine CD38 gene. Overexpression of CD38 protein level in DCs induced from bone-marrow derived DCs (BMDCs) by recombinant mouse granulocyte macrophage colony-stimulating factor and IL-4 was achieved through 24 h adenovirus infection. The results demonstrated that BMDCs with CD38 overexpression exhibited no phenotypic change; however, following stimulation with lipopolysaccharide (LPS), maturation and IL-12 secretion were increased. In addition, CD38-overexpressing BMDCs stimulated with LPS exhibited more effective Th1 cell differentiation. Mice that were administered CD38 overexpressing BMDCs exhibited milder symptoms of asthma. Furthermore, decreased IL-4, IL-5 and IL-13 levels were detected in bronchoalveolar lavage fluid (BALF), reduced immunoglobulin E levels were measured in the sera, and increased interferon-gamma was detected in BALF from the recipients of CD38-overexpressing BMDCs. Increased phosphorylated-p38 expression was also detected in LPS stimulated CD38-overexpressing BMDCs, whereas pretreatment with a p38-specific inhibitor was able to abolish the effects of LPS stimulation and CD38 overexpression on IL-12 release and Th1 cell differentiation in BMDCs. These results suggested that CD38 may be involved in the DC function of alleviating asthma via restoration of the Th1/Th2 balance, thus providing a novel strategy for asthma therapy. PMID- 27666022 TI - Excellent magnetocaloric properties in RE2Cu2Cd (RE = Dy and Tm) compounds and its composite materials. AB - The magnetic properties and magnetocaloric effect (MCE) of ternary intermetallic RE2Cu2Cd (RE = Dy and Tm) compounds and its composite materials have been investigated in detail. Both compounds undergo a paramagnetic to ferromagnetic transition at its own Curie temperatures of TC ~ 48.5 and 15 K for Dy2Cu2Cd and Tm2Cu2Cd, respectively, giving rise to the large reversible MCE. An additionally magnetic transition can be observed around 16 K for Dy2Cu2Cd compound. The maximum values of magnetic entropy change (-DeltaSMmax) are estimated to be 17.0 and 20.8 J/kg K for Dy2Cu2Cd and Tm2Cu2Cd, for a magnetic field change of 0-70 kOe, respectively. A table-like MCE in a wide temperature range of 10-70 K and enhanced refrigerant capacity (RC) are achieved in the Dy2Cu2Cd - Tm2Cu2Cd composite materials. For a magnetic field change of 0-50 kOe, the maximum improvements of RC reach 32% and 153%, in comparison with that of individual compound Dy2Cu2Cd and Tm2Cu2Cd. The excellent MCE properties suggest the RE2Cu2Cd (RE = Dy and Tm) and its composite materials could be expected to have effective applications for low temperature magnetic refrigeration. PMID- 27666021 TI - FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties. AB - Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters gamma-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium. Furthermore, new GABABRs are synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABABR expression, dendritic signalling, and antidepressant efficacy are absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following alcohol exposure, providing a molecular basis for the antidepressant efficacy of acute ethanol exposure. PMID- 27666023 TI - [Corrigendum] Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells. AB - Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Figs. 2 and 3. Essentially, there was a direct duplication of certain of the western blotting data between Fig. 2 (the E-cadherin and Actin data) and Fig. 3C (the Zyxin and Actin data). After having re-examined our original data, we realize that we inadvertently duplicated the data from Fig. 2 in Fig. 3C (the Zyxin and Actin data). A corrected version of Fig. 3C (containing the true Zyxin and Actin data), and, by natural process, also of Fig. 6, are presented below, in which the Zyxin data in Figs. 3C and 6 are now correctly shown. Since the Zyxin data was a control for the siZyxin knockout of HOC313, this error did not affect the results of the Rho family analysis in this study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the International Journal of Oncology 42: 873 880, 2013; DOI: 10.3892/ijo.2013.1761]. PMID- 27666024 TI - Macmillan nurses: fighting cancer with more than medicine. AB - The aim of this Learning Unit is to develop nurses' understanding of the role and function of Macmillan nurses so that they can identify for whom, and in what circumstances, referral to a Macmillan nurse is appropriate. PMID- 27666025 TI - If only***. AB - If only... it is difficult not to consider the Clothier Report into the Beverly Allitt case without hearing the echo of these treacherous words. For staff at Grantham and Kesteven Hospital - nurses, doctors and managers alike - it must be difficult not to look back in anguish and wonder how much influence they could have had in altering the sequence of events that led to the deaths of four children. PMID- 27666026 TI - Union fears Allitt inquiry findings will gather dust through shortage of cash. AB - The Clothier Inquiry into the Beverley Allitt murders has made a series of sweeping recommendations which are destined to affect how nurses are screened before being allowed into the profession. PMID- 27666027 TI - ? AB - Four-year-old orphan twins, Nathan and Neressa, aided by Anneka Rice, helped Bamardo's and Help the Aged to launch a joint fundraising campaign for families under pressure last week. The Sharing the Caring scheme Ls part of the International Year of the Family. Rukiyajemmott, a social worker from Harambee Family Support Centre in Brixton, also attended the event, held at Madame Tussaud's. PMID- 27666028 TI - PREP to change. AB - Substantial modifications to the UKCC's PREP proposals are likely to be agreed at next week's Council meeting. PMID- 27666015 TI - Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. AB - Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative(r), announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine. PMID- 27666029 TI - Government U-turn sinks Guy's but saves the Marsden. AB - Health Secretary Virginia Bottomley has refused to say how many nurses will lose their jobs after her latest announcement on the future of London's health services. PMID- 27666030 TI - Up to 1,000 jobs at risk in Scotland. AB - Up to 1,000 nursing jobs could go in a shake-up of acute and maternity services in Scotland, Unison warned last week. PMID- 27666032 TI - UKCC concern over redeployment. AB - The UK Central Council is set to condemn trusts and health authorities seeking to redeploy enrolled nurses as health care assistants. PMID- 27666033 TI - Bursary to help minority ethnic groups. AB - A new nursing award, aimed at improving health services for minority ethnic groups, was launched by Health Minister Brian Mawhinney at the RCN last week. PMID- 27666034 TI - Students 'negative' on cancer. AB - Student nurses hold negative attitudes towards cancer and associate the disease with inevitable death, a Royal College of Nursing consensus conference heard last week. PMID- 27666035 TI - Labour plans for complaints overhaul. AB - The Labour Party would undertake a review of the United Kingdom Central Council as part of a revision of complaints procedures, Shadow Health Secretary David Blunkett said last week. PMID- 27666036 TI - New meeting on health campaign. AB - Officers from the RCN in Northern Ireland and the Province's health department are to meet again to discuss the findings of the College's Making It Better campaign. PMID- 27666037 TI - Anger at DoH failure to check racism. AB - Nursing unions fear the government is reneging on proposals to monitor clinical grading appeals for possible racial discrimination. PMID- 27666038 TI - ? AB - A precious porcelain figurine has been lent to the RCN by the Queen Alexandra's Royal Army Nursing Corps. Brigadier Dixon-Nuttall. Matron-in-Chief, QARANC, noticed at an RCN dinner the absence of a QARANC model among the collection of service figurines. It was presented on her behalf to Ros Fraser, Deputy RCN President. PMID- 27666039 TI - Union protests force rethink on Birmingham health review. AB - Protests from nursing unions and other pressure groups have forced health authorities in Birmingham to amend plans for a Tomlinson-style review of the city's health services. PMID- 27666040 TI - Survey reveals falling morale. AB - Three in five professional and technical staff in the national health service have considered quitting in the past year, a survey by the health union Unison revealed last week. PMID- 27666041 TI - Warning over sacked worker. AB - Ashworth Hospital's decision to sack a senior social worker for allegedly supplying an electronics catalogue to a patient could set a dangerous precedent, a union officer has warned. PMID- 27666042 TI - RCM outrage at pool birth decision. AB - A trust's decision to discipline two midwives for granting a mother's wish for a water delivery has been denounced as 'unjust, unprecedented and unacceptable' by the Royal College of Midwives. PMID- 27666043 TI - ? AB - Germane experience: Six Welsh student nurses are mastering the German language In preparation for an exchange visit to Osnabruck in the spring. It is one of the first international exchange schemes in the UK to involve diploma nursing students. The students, from the Department of Nursing and Midwifery at the University of Glamorgan, will spend 15 weeks sharing practical and theoretical knowledge with German nurses. They will work in surgical, care of the elderly and paediatric areas. PMID- 27666045 TI - Senior Rampton nurse dies of cancer. AB - Richard Ferry, the driving force behind the establishment of the Nursing Development Unit at Rampton Hospital, has died of cancer at the age of 35. PMID- 27666044 TI - Win a trip to Hawaii. AB - Nursing Standard is offering the chance to win a fortnight's holiday in Hawaii. Fill in the enclosed readership survey, and if you opt to give us your name and address you will be entered for the holiday prize draw. PMID- 27666046 TI - RCN in deals with university unions. AB - The Royal College of Nursing is to join forces with the National Association of Teachers in Further Education and the Association of University Teachers. PMID- 27666047 TI - Nursing practice award puts children's rights into the health care equation. AB - Immediate intervention by health professionals can damage the rehabilitation of sexually abused children, Gerison Lansdown, the Director of the Children's Rights Development Unit, said last week. PMID- 27666048 TI - Audit brings prisons into line. AB - Prison health care units are to be asked to complete an audit of nursing services in a bid to bring them into line with standards in the NHS. PMID- 27666049 TI - Fingertip accident. AB - Managers at the Royal Manchester Children's Hospital have refused to confirm whether disciplinary action will be taken against a nurse who is alleged to have accidentally cut off a baby's fingertip. PMID- 27666050 TI - Information pack on prostitution. AB - An information pack for nurses and others working with drugusing prostitutes has been published by Manchester University's Department of Nursing. PMID- 27666051 TI - Early warning signals. AB - The frightening prospect of what could happen when trust managers get their hands on local pay, terms and conditions has been revealed in all its glory. The progress of a set of proposals from a Mid-lands trust is being followed by managers in other units as a potential model for the introduction of performance related pay and local pay bargaining. PMID- 27666052 TI - Committed to serve. AB - Nursing is a ticket to travel the world. for some this involves working in Australia or America, but for those who gathered to celebrate the diversity of nursing at the Florence Nightingale Museum, it meant travelling to far less hospitable places - those torn apart by war. PMID- 27666053 TI - Bailiwick battle. AB - When people hear that worked Guernsey for 17 years, they often respond by saying how lucky I am. But all is not as it seems. The island's health care system is not part of the NHS. It has a non- party system of government and a great deal of UK legislation does not apply: in particular that governing equal pay, equal opportunities and employment protection. PMID- 27666055 TI - Lily livers must watch their assets. AB - Let's get one thing straight. The Patient's Charter is nothing to do with a patient's right to efficient, decent health care. It is a vehicle used by management and government to attack NHS staff. PMID- 27666054 TI - Back to basic bedside ministering. AB - I have to question whether the 'academics' who are forcing this so-called professionalism onto nurses either know or remember what it is like to be in the real world of hands-on nursing. PMID- 27666056 TI - Robo-support worker invades IJKCC turf. AB - Unfortunately, due to some misreporting of my paper to the Society of Occupational Health Nurses, the two nurses who commented on your news article neither grasped the point, nor the concepts of occupational health practice (There's no need to envy NVQs, Taken further to task over NVQs, Letters, January 12). PMID- 27666058 TI - We interrupt this program(me). AB - May 1 remind you that we live in Great Britain, not the United States of America. PMID- 27666057 TI - Sky diver in Jersey lacks NHS support. AB - I'm afraid I did not find Jon Gould's clinical article, The impact of change on violent patients (February 2) helpful. PMID- 27666059 TI - Lofty ambitions need DIY conversions. AB - S Collins asked how she can get support for her EN conversion course (Information Exchange, February 2). The answer is to pay for yourself, if you can't get your employer to help. PMID- 27666060 TI - Information exchange. AB - *We have established an enrolled nurse support group, aimed at identifying local ENs' needs and obtaining information on further training opportunities. PMID- 27666061 TI - Support workers say no to nurses' shoes. AB - I must respond to Anna Barret's Viewpoint article, Bendable or expendable (January 26), by arguing that perceiving support workers as a 'threat' is both illogical and a slight on the characters of the personnel in these posts. PMID- 27666062 TI - NUS needs nursing nous now. AB - The National Union of Students annual conference is held at Easter each year, but so far very few student nurses have attended it. PMID- 27666063 TI - Gossip. AB - Till death us do parts: if bereavement were not enough of an unhinging experience already, more than 40 per cent of the population may in future have to be dismantled before meeting their maker - in the interests of environmental friendliness. PMID- 27666064 TI - Practice nursing - stability and change Practice nursing - stability and change M Damant C Martin S Openshaw C V Mosby 128pp L9.95 0-7234-1882-9. AB - Practice Nursing is a comprehensive book examining the many, varied and current issues regarding the scope of practice nursing within general practice. The aim is to inspire practice nurses to provide a high quality service to meet the changing health needs of the population. PMID- 27666065 TI - Research in health promotion and nursing Research in health promotion and nursing J Wilson-Bamett and J Macleod-Clark editors Macmillan 282pp L12.99 0-333-60134-3 [Formula: see text]. AB - As suggested by its title, the text concentrates on the interface between research and health promotion. The contributors are from a variety of backgrounds in the health- science related fields, nationally as well as internationally. PMID- 27666066 TI - Improving assessment in rehabilitation and health Improving assessment in rehabilitation and health R L Glueckauf et al, editors SAGE Publications 334pp L17.95 0-8039-5085-3 [Formula: see text]. AB - Improving Assessment in Rehabilitation and Health is essentially about research in the field of psychological assessment. Robert Glueckauf and his colleagues' primary objective is to 'heighten the sensitivity of practitioners and graduate students to the conceptual and methodological problems' which affect the quality of assessment in rehabilitation. PMID- 27666068 TI - Women's lip. AB - As nurses get to grips with the implications of the latest pay award, there is news of an organisation designed to enable women to identify and cope with financial responsibilities and the opportunities available to them. PMID- 27666067 TI - Network Factfile. PMID- 27666069 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road. Harrow. Middlesex HA 1 2AX. Fax: 081-423 3867. PMID- 27666070 TI - Working backwards: Can variations in neonatal outcomes help identify best practice? PMID- 27666072 TI - Gasping for air. PMID- 27666071 TI - Making the most of the single-family-room NICU. PMID- 27666073 TI - Shaken baby syndrome and abusive head trauma are real problems. PMID- 27666074 TI - "Loose joints". PMID- 27666075 TI - Neonatal intubation training: the patient comes first. PMID- 27666076 TI - 50 Years Ago in TheJournal ofPediatrics: The Suppression of A2 Influenza in Children by the Chemoprophylactic Use of Amantadine. PMID- 27666078 TI - Corrections. PMID- 27666077 TI - 50 Years Ago in TheJournal ofPediatrics: Evaluation of the Effects of Terminating the Diet in Phenylketonuria. PMID- 27666079 TI - Corrections. PMID- 27666080 TI - Views of the presidents of national European pediatric societies on evolving challenges of child health care. PMID- 27666081 TI - Self-Assembly of Amphiphilic Block Copolypeptoids - Micelles, Worms and Polymersomes. AB - Polypeptoids are an old but recently rediscovered polymer class with interesting synthetic, physico-chemical and biological characteristics. Here, we introduce new aromatic monomers, N-benzyl glycine N-carboxyanhydride and N-phenethyl glycine N-carboxyanhydride and their block copolymers with the hydrophilic polysarcosine. We compare their self-assembly in water and aqueous buffer with the self-assembly of amphiphilic block copolypeptoids with aliphatic side chains. The aggregates in water were investigated by dynamic light scattering and electron microscopy. We found a variety of morphologies, which were influenced by the polymer structure as well as by the preparation method. Overall, we found polymersomes, worm-like micelles and oligo-lamellar morphologies as well as some less defined aggregates of interconnected worms and vesicles. Such, this contribution may serve as a starting point for a more detailed investigation of the self-assembly behavior of the rich class of polypeptoids and for a better understanding between the differences in the aggregation behavior of non-uniform polypeptoids and uniform peptoids. PMID- 27666082 TI - Expression-based GWAS identifies variants, gene interactions and key regulators affecting intramuscular fatty acid content and composition in porcine meat. AB - The aim of this work is to better understand the genetic mechanisms determining two complex traits affecting porcine meat quality: intramuscular fat (IMF) content and its fatty acid (FA) composition. With this purpose, expression Genome Wide Association Study (eGWAS) of 45 lipid-related genes associated with meat quality traits in swine muscle (Longissimus dorsi) of 114 Iberian * Landrace backcross animals was performed. The eGWAS identified 241 SNPs associated with 11 genes: ACSM5, CROT, FABP3, FOS, HIF1AN, IGF2, MGLL, NCOA1, PIK3R1, PLA2G12A and PPARA. Three expression Quantitative Trait Loci (eQTLs) for IGF2, ACSM5 and MGLL were identified, showing cis-acting effects, whereas 16 eQTLs had trans regulatory effects. A polymorphism in the ACSM5 promoter region associated with its expression was identified. In addition, strong candidate genes regulating ACSM5, FOS, PPARA, PIK3R1, PLA2G12A and HIF1AN gene expression were also seen. Notably, the analysis highlighted the NR3C1 transcription factor as a strong candidate gene involved in the regulation of the 45 genes analysed. Finally, the IGF2, MGLL, MC2R, ARHGAP6, and NR3C1 genes were identified as potential regulators co-localizing within QTLs for fatness and growth traits in the IBMAP population. The results obtained increase our knowledge in the functional regulatory mechanisms involved in these complex traits. PMID- 27666083 TI - Searching for wisdom in oncology care: A scoping review. AB - OBJECTIVE: The concept of "wisdom" is beginning to emerge in the oncology literature, raising questions concerning: (1) how the concept of wisdom is used in oncology literature; (2) the ways in which wisdom has been a focus of inquiry within oncology care; and (3) how wisdom is characterized when the term is used. METHOD: A scoping review, using Arksey and O'Malley's five-step framework, was undertaken to address these questions. In consultation with oncology reference librarians, "wisdom"- and "oncology"-related search terms were identified, and four electronic databases were searched: CINAHL, SocINDEX, PubMed, and PsychINFO. After removal of duplicates and application of inclusion and exclusion criteria, 58 records were identified and included for analysis. RESULTS: The concept of wisdom was employed with a breadth of meanings, and 58 records were schematized into 7 genres, including: (1) empirical research with wisdom foregrounded as a study focus (n = 2); (2) empirical research articles where "wisdom" appears in the findings (n = 16); (3) a quality-improvement project where wisdom is an embedded concept (n = 1); (4) essays where wisdom is an aspect of the discussion (n = 5); (5) commentary/opinion pieces where wisdom is an aspect of its focus (n = 6); (6) personal stories describing wisdom as something gleaned from lived experience with cancer (n = 2); and (7) everyday/taken-for-granted uses of wisdom (n = 26). SIGNIFICANCE OF RESULTS: The notion of wisdom has a taken-for-granted presence in the published oncology literature and holds promise for future research into patient and clinician wisdom in oncology care. Nonetheless, the terminology is varied and unclear. A scholarly focus on wisdom has not been brought to bear in cancer care to the degree it has in other fields, and research is in the early stages. Various characterizations of wisdom are present. If such a resource as "wisdom" exists, dwelling in human experiences and practices, there may be benefit in recognizing wisdom as informing the epistemologies of practice in oncology care. PMID- 27666085 TI - Flocculation kinetics of low-turbidity raw water and the irreversible floc breakup process. AB - The main objective of this study was to propose an improvement to the flocculation kinetics model presented by Argaman and Kaufman, by including a new term that accounts for the irreversible floc breakup process. Both models were fitted to the experimental results obtained with flocculation kinetics assays of low turbidity raw water containing Microcystis aeruginosa cells. Aluminum sulfate and ferric chloride were used as coagulants, and three distinct average velocity gradient (G) values were applied in the flocculation stage (20, 40 and 60 s-1). Experimental results suggest that the equilibrium between the aggregation and breakup process, as depicted by Argaman and Kaufman's original model, might not be constant over time, since the residual turbidity increased in various assays (phenomenon that was attributed to the irreversible floc breakup process). In the aluminum sulfate assays, the residual turbidity increase was visible when G = 20 s-1 (dosages of 60 and 80 mg L-1). For the ferric chloride assays, the phenomenon was noticed when G = 60 s-1 (dosages of 60 and 80 mg L-1). The proposed model presented a better fit to the experimental results, especially at higher coagulant dosages and/or higher values of average velocity gradient (G). PMID- 27666084 TI - Primary Health Care Providers' Perspectives: Facilitating Older Patients' Access to Community Support Services. AB - The purpose of the study examined in this article was to understand how non physician health care professionals working in Canadian primary health care settings facilitate older persons' access to community support services (CSSs). The use of CSSs has positive impacts for clients, yet they are underused from lack of awareness. Using a qualitative description approach, we interviewed 20 health care professionals from various disciplines and primary health care models about the processes they use to link older patients to CSSs. Participants collaborated extensively with interprofessional colleagues within and outside their organizations to find relevant CSSs. They actively engaged patients and families in making these linkages and ensured follow-up. It was troubling to find that they relied on out-of-date resources and inefficient search strategies to find CSSs. Our findings can be used to develop resources and approaches to better support primary health care providers in linking older adults to relevant CSSs. PMID- 27666087 TI - Automated Internal Classification of Beadless Chinese ZhuJi Freshwater Pearls based on Optical Coherence Tomography Images. AB - Optical coherence tomography (OCT) has been applied to inspect the internal defect of beadless Chinese ZhuJi fleshwater pearls. A novel fully automated algorithm is proposed to classify between normal and defective sub-layer in nacre layer. Our algorithm utilizes the graph segmentation approach to estimate the up and down boundaries of defect sub-layers from flattened and cropped image, and also proposes the strategy for edge and weight construction in segmentation process. The vertical gradients of boundary pixels are used to make grading decision. The algorithm is tested by typical pearl samples, and achieves 100% classification accuracy. The experiment result shows the feasibility and adaptability of the proposed approach, and proves that the OCT technique combined with proposed algorithm is a potential tool for fast and non-destructive diagnosis of internal structure of beadless pearl. PMID- 27666086 TI - Effectiveness of Kobayashi plug for 252 ears with chronic patulous Eustachian tube. AB - CONCLUSIONS: Trans-tympanic plugging of the Eustachian tube (ET) with the silicone plug (Kobayashi Plug) induced long-term effectiveness for over 80% of chronic and severe patulous ET (PET) patients. The New Kobayashi Plug was more effective with fewer complication of plug descent to the pharyngeal orifice. OBJECTIVE: To investigate the effectiveness and complications of trans-tympanic plugging of the ET using a Kobayashi Plug for chronic PET. METHOD: Trans-tympanic plugging of the ET using the Kobayashi Plug was performed for 252 ears of 191 patients. The Prototype Plug (115 ears of 82 patients in 2001-2007) and the New Plug (137 ears of 109 patients in 2008-2013) were inserted for chronic PET patients. RESULTS: The success rate of the Kobayashi Plug for PET was 83.0% of a total (Prototype Plug 80.0%, New Plug 85.4%). In 26 ears, the Prototype Plugs were found to have descended toward the nasopharynx. Conversely, this did not happen with the New Plug. The rate of TM perforation (Prototype 22.6%, New 17.5%), middle ear effusion (Prototype 20.2%, New 10.2%) and ventilation tube placement (Prototype 14.8%, New 4.4%) decreased after transition to the New Plug. PMID- 27666088 TI - DNA barcoding reveals that the common cupped oyster in Taiwan is the Portuguese oyster Crassostrea angulata (Ostreoida; Ostreidae), not C. gigas. AB - The Pacific cupped oyster, Crassostrea gigas, is one of the major aquacultural shellfish species that has been introduced to Europe and America from its native source in the West Pacific. In Taiwan, the cultivated cupped oysters along the west coast have been identified as C. gigas for over centuries; however, several molecular phylogenetic studies have cast doubt upon the existence of this species in Taiwan and adjacent waters. Indeed, our analyses of mitochondrial cytochrome oxidase I (COI) sequences from 313 Crassostrea collected from 12 locations along Taiwanese and southern Chinese coastlines confirm that all samples were the Portuguese oyster, C. angulata, rather than C. gigas. Multiple lines of evidence, including haplotypic and nucleotide diversity of the COI gene, demographic history, and population genetics, suggest that Taiwanese C. angulata is unique, probably experienced a sudden population expansion after the Last Glacial Maxima around 20,000 years ago, and has a significantly limited genetic connectivity across the Taiwan Strait. Our study applies an extended sampling and DNA barcoding to confirm the absence of C. gigas in natural and cultivated populations in Taiwan and southern China, where we only found C. angulata. We highlight the importance of conserving the gene pool of the C. angulata population in Taiwan, particularly considering the current threats by large-scale environmental disturbances such as marine pollution, habitat destruction, and climate change. PMID- 27666089 TI - Protein characterization of intracellular target-sorted, formalin-fixed cell subpopulations. AB - Cellular heterogeneity is inherent in most human tissues, making the investigation of specific cell types challenging. Here, we describe a novel, fixation/intracellular target-based sorting and protein extraction method to provide accurate protein characterization for cell subpopulations. Validation and feasibility tests were conducted using homogeneous, neural cell lines and heterogeneous, rat brain cells, respectively. Intracellular proteins of interest were labeled with fluorescent antibodies for fluorescence-activated cell sorting. Reproducible protein extraction from fresh and fixed samples required lysis buffer with high concentrations of Tris-HCl and sodium dodecyl sulfate as well as exposure to high heat. No deterioration in protein amount or quality was observed for fixed, sorted samples. For the feasibility experiment, a primary rat subpopulation of neuronal cells was selected for based on high, intracellular beta-III tubulin signal. These cells showed distinct protein expression differences from the unsorted population for specific (phosphorylated tau) and non-specific (total tau) protein targets. Our approach allows for determining more accurate protein profiles directly from cell types of interest and provides a platform technology in which any cell subpopulation can be biochemically investigated. PMID- 27666090 TI - Evaluating digestion efficiency in full-scale anaerobic digesters by identifying active microbial populations through the lens of microbial activity. AB - Anaerobic digestion is a common technology to biologically stabilize wasted solids produced in municipal wastewater treatment. Its efficiency is usually evaluated by calculating the reduction in volatile solids, which assumes no biomass growth associated with digestion. To determine whether this assumption is valid and further evaluate digestion efficiency, this study sampled 35 digester sludge from different reactors at multiple time points together with the feed biomass in a full-scale water reclamation plant at Chicago, Illinois. The microbial communities were characterized using Illumina sequencing technology based on 16S rRNA and 16S rRNA gene (rDNA). 74 core microbial populations were identified and represented 58.7% of the entire digester community. Among them, active populations were first identified using the ratio of 16S rRNA and 16S rDNA (rRNA/rDNA) for individual populations, but this approach failed to generate consistent results. Subsequently, a recently proposed mass balance model was applied to calculate the specific growth rate (MU), and this approach successfully identified active microbial populations in digester (positive MU) that could play important roles than those with negative MU. It was further estimated that 82% of microbial populations in the feed sludge were digested in comparison with less than 50% calculated using current equations. PMID- 27666091 TI - Acoustic-temporal aspects of stop-plosives in the speech of Persian-speaking children with cleft lip and palate. AB - PURPOSE: The main objective was to examine temporal parameters of stop-plosives in Persian-speaking children with repaired cleft lip and palate (CLP). METHOD: Eleven children with repaired bilateral CLP and 20 typically-developing children participated in the study. Stop-gap duration (SGD) and voice-onset time (VOT) were measured based on digital waveform and spectrographic displays. RESULT: Separate linear mixed model analyses showed significantly longer SGDs for children with CLP for all plosives in word-mid and final positions. Furthermore, children with CLP tend to produce longer VOTs for all voiceless plosives. CONCLUSION: Persian-speaking children with repaired CLP prolong stop-gap segments, similar to findings reported for English-speaking children with CLP. Prolonged segments may be due to an active strategy to increase oral air pressure and/or improve perceptual accuracy of speech segments. PMID- 27666092 TI - An ab initio study of the polytypism in InP. AB - The existence of polytypism in semiconductor nanostructures gives rise to the appearance of stacking faults which many times can be treated as quantum wells. In some cases, despite of a careful growth, the polytypism can be hardly avoided. In this work, we perform an ab initio study of zincblende stacking faults in a wurtzite InP system, using the supercell approach and taking the limit of low density of narrow stacking faults regions. Our results confirm the type II band alignment between the phases, producing a reliable qualitative description of the band gap evolution along the growth axis. These results show an spacial asymmetry in the zincblende quantum wells, that is expected due to the fact that the wurtzite stacking sequence (ABAB) is part of the zincblende one (ABCABC), but with an unexpected asymmetry between the valence and the conduction bands. We also present results for the complex dielectric function, clearly showing the influence of the stacking on the homostructure values and surprisingly proving that the correspondent bulk results can be used to reproduce the polytypism even in the limit we considered. PMID- 27666093 TI - NHS England's HIV scandal. PMID- 27666094 TI - The Missing Type campaign. PMID- 27666095 TI - Using a change model to reduce the risk of surgical site infection. AB - A surgical site infection (SSI) surveillance module completed in 2014 highlighted that infection rates for breast surgery inpatients and readmissions at an acute trust had increased to 2.2%, from 0.5% in 2012. The national benchmark for 2014 established by Public Health England (PHE) was 1.0%. This demonstrated a greater than fourfold absolute increase in SSI for breast surgery during these periods. The infection rate could have been due to chance, but warranted investigation. The results were presented to the breast team and used to drive practice transformation through audit and observation, identifying areas of change to improve patient safety. The project used a recognised 8-step model for leading change developed by John Kotter, a professor at Harvard Business School and world renowned change expert. The project presented opportunities to promote infection prevention while implementing care improvement strategies and behaviour change in partnership with the breast team. PMID- 27666096 TI - Assessment and management of the septic patient: part 1. AB - Sepsis has gained increasing publicity in recent years, and is now a strong focus of clinical education and training following the launch of the 'Surviving Sepsis' campaign. The assessment and management of a septic patient are far from simple and requires a systematic approach in both identifying and managing the condition. This two-part series explores the assessment and management of a septic patient, with this article emphasising the need to identify the signs and symptoms of sepsis at the early stages if positive patient outcomes are to be realised. The ABCDE approach to patient assessment is explored in the context of sepsis, as this approach can ensure the nurse will identify sepsis as opposed to the basic method of only performing vital observations. PMID- 27666097 TI - Using health psychology to help patients: common mental health disorders and psychological distress. AB - This article provides an overview of how health psychology can be used by nurses to help patients experiencing common mental health problems and psychological distress. Mental health problems are common and are associated with poor outcomes, especially for patients with comorbid physical health conditions. Mental health problems are associated with unhealthy behaviours such as smoking, physical inactivity, overeating and excessive alcohol use, which will result in poorer outcomes for patients. Consideration of a patient's psychological health is therefore important for all nurses providing holistic care. Awareness of the symptoms of psychological distress, good communication skills and simple screening instruments can be used by nurses to assess patients' mental health. The cognitive and behavioural risk factors associated with depression and anxiety are also explored, as an understanding of these can help nurses to provide appropriate care. PMID- 27666098 TI - Garden hazards: trampoline injuries. AB - Trampolining is more popular than ever, but it can also cause injuries, some of them very serious. Siba Prosad Paul, Torbay Hospital, Torquay, Joanna Barnden, University of Bristol, and Meridith Kane, Yeovil District Hospital, discuss what can be done to prevent them. PMID- 27666099 TI - Female genital mutilation and pregnancy: associated risks. AB - Female genital mutilation (FGM) is a traditional practice that has no medical benefit and severe health consequences for girls and women. This article discusses the risks to patients who are pregnant and have had FGM. It will describe urinary tract infections caused by FGM, and how this condition increases the risk of preterm labour and delivery. It will also address the difficulty in vaginal examinations that can be caused by FGM and instances when this can delay diagnosis and treatment. In addition, it will explore a number of intrapartum risks caused by FGM and the role of deinfibulation in pregnancy. Finally, it will look at the link between maternal and fetal morbidity and mortality, and FGM. PMID- 27666100 TI - Childhood obesity plan: the Government declares war on sugar. AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses the latest Government initiative to tackle the rising levels of childhood obesity in the UK. PMID- 27666101 TI - Children's nursing: patient safety and clinical risk in neonatal care. AB - John Tingle, Reader in Health Law at Nottingham Trent University, discusses a recent publication by the Care Quality Commission (CQC) that looks at identifying and managing clinical risks in newborn babies. PMID- 27666102 TI - Deprivation of liberty and covert medicines: practice implications. AB - Richard Griffith, Senior Lecturer in Health Law at Swansea Univeristy, considers a recent decision by the Court of Protection. PMID- 27666103 TI - Should I stay or should I go? Stress, burnout and nurse retention. AB - Janet Scammell, Associate Professor (Nursing), Bournemouth University looks at problems retaining nurses. PMID- 27666104 TI - Normalising the abnormal is no good. AB - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, considers the issues around staffing and the importance of being open about challenges. PMID- 27666105 TI - Care and management of a stoma: maintaining peristomal skin health. AB - It is estimated that around one in 500 people in the UK are living with a stoma, with approximately 21 000 operations that result in stoma formation being performed each year ( Colostomy Association, 2016 ). These people face a unique set of challenges in maintaining the integrity of their peristomal skin. This article explores the normal structure and function of skin and how the care and management of a stoma presents challenges for maintaining peristomal skin health. Particular focus is paid to the incidence of skin problems for those living with a stoma, whether it is temporary or permanent, and the factors that contribute to skin breakdown in this population. Wider factors such as the central role of the clinical nurse specialist and the impact of product usage on positive outcomes and health economics are also considered. PMID- 27666106 TI - Stoma Care Nurse of the Year Runner up 2016. PMID- 27666107 TI - How stoma care nursing has changed over the course of one nurse's career. AB - Pat Black, Associate Lecturer, Birmingham City University and previously Senior Lecturer, St Mark's Institute for Gastrointestinal Nursing, looks back at the origins of stoma care nursing and ponders what the future might hold. PMID- 27666108 TI - Intimacy for patients with a stoma. AB - Jennie Burch, Enhanced Recovery Nurse Facilitator, St Marks Hospital, Middlesex, looks at what nurses can do to support patients after stoma formation in relation to body image and intimacy. PMID- 27666109 TI - A reflection on safeguarding in practice. AB - Safeguarding is about the protection of the most vulnerable people in our society. This article presents a case history of the author's experience of a patient with a colostomy and high-output abdominal fistula, who was involved in a safeguarding alert. It explores the roles and responsibilities of nurses, regardless of specialty, to increase their awareness, understanding and knowledge of safeguarding, and the processes in place to protect the most vulnerable people they care for. PMID- 27666110 TI - Resilience and collaboration. PMID- 27666111 TI - Quality of life, wellbeing and care needs of Irish ostomates. AB - Having a stoma can reduce a person's quality of life and cause distress. A survey of people in Ireland who have had a stoma for an average of 15 years found that, while they now have a similar quality of life to the general population, they have poorer mental health and a higher level of sexual dysfunction. Respondents want to talk about their experiences and may benefit from more opportunities to talk to others with a stoma or to stoma care nurses. While most patient information suggests that patients can return to their usual diet and their clothes, a majority of ostomates have to make changes in these areas; some dietary changes have implications for their health. Ostomates in Ireland experience continuing problems with leakages and peristomal skin. These issues show there is a need for routine, regular follow up of ostomates by stoma care nurses. Although most patients found follow up by a community stoma care nurse helpful, the provision of this type of service varies. PMID- 27666112 TI - Evaluation of monitoring strategies for childhood asthma. AB - INTRODUCTION: The goal of monitoring pediatric asthma is to obtain and maintain asthma control, which is defined as minimizing asthma symptoms, restrictions to daily activities and the use of rescue medication. Long term goals include reducing the risk of fixed airflow limitation, and preventing asthma exacerbations and side effects of treatment. Several monitoring tools are available but no consensus exists on how to monitor patients in the most optimal way. Areas covered: In this review, we provide an overview of different tools and address general considerations on monitoring childhood asthma. Asthma care should be tailored to the individual patient. The health care professional should decide which monitoring strategy and frequency is optimal for the individual patient. Expert commentary: Personalized medicine should be the key issue in monitoring asthma in children. It is crucial to monitor disease activity and deterioration but there is no monitoring strategy that is clearly superior compared to others: The optimal strategy and frequency will vary between patients. Actually, both treatment and monitoring of pediatric asthma probably benefit from a personalized approach. PMID- 27666113 TI - Congenital cystic adenomatoid malformation of the lung (CCAM), a retrospective clinical audit and literature review in a tertiary centre in Scotland over a period of 14 years. AB - This work was a retrospective audit of CCAM - 1994 to 2008. A total of 26 cases were identified. Mean gestational age at diagnosis was 20 weeks. All were unilateral and had serial scans. In 31% the lesion resolved, 8% decreased, 42% were unchanged and 4% increased in size. Only one foetus developed hydrops. All were born alive. Of 8 foetuses where the CCAM was thought to have resolved, 6 had persistent lesions (overall sensitivity and PPV of US 64% and 69%, respectively). Computerised tomography performed better than chest X-ray in detecting lesions postnatally (sensitivity 100% vs 88%, PPV 95% vs 78%). Seventeen cases required surgery, 4 conservative management and 2 were discharged following negative CXR; 12% had associated anomalies. Four babies had recurrent chest infections. CCAMs have a good overall prognosis. CT scan rather than CXR should be performed to confirm the resolution of antenatally diagnosed lesions. Surgical management is the preferred option over conservative management. PMID- 27666114 TI - Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study. AB - BACKGROUND: The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are - in hindsight - unnecessarily exposed to a small but realistic risk of severe endoscopy associated complications. We developed a diagnostic strategy to better exclude SCD in these patients and evaluated the value of adding a faecal calprotectin point-of-care (POC) and/or a POC faecal immunochemical test for haemoglobin (FIT) to routine clinical information. METHODS: We used data from a prospective diagnostic study in SCD-suspected patients from 266 Dutch primary care practices referred for endoscopy to develop a diagnostic model for SCD with routine clinical information, which we extended with faecal calprotectin POC (quantitatively in MUg/g faeces) and/or POC FIT results (qualitatively with a 6 MUg/g faeces detection limit). We defined SCD as colorectal cancer (CRC), inflammatory bowel disease, diverticulitis, or advanced adenoma (>1 cm). RESULTS: Of 810 patients, 141 (17.4 %) had SCD. A diagnostic model with routine clinical data discriminated between patients with and without SCD with an area under the receiver operating characteristic curve (AUC) of 0.741 (95 % CI, 0.694-0.789). This AUC increased to 0.763 (95 % CI, 0.718-0.809; P = 0.078) when adding the calprotectin POC test, to 0.831 (95 % CI, 0.791-0.872; P < 0.001) when adding the POC FIT, and to 0.837 (95 % CI, 0.798-0.876; P < 0.001) upon combined extension. At a >= 5.0 % SCD probability threshold for endoscopy referral, 30.4 % of the patients tested negative based on this combined POC-tests extended model (95 % CI, 25.7-35.3 %), with 96.4 % negative predictive value (95 % CI, 93.1-98.2 %) and 93.7 % sensitivity (95 % CI, 88.2-96.8 %). Excluding the calprotectin POC test from this model still yielded 30.1 % test negatives (95 % CI, 24.7-35.6 %) and 96.0 % negative predictive value (95 % CI, 92.6-97.9 %), with 93.0 % sensitivity (95 % CI, 87.4-96.4 %). CONCLUSIONS: FIT - and to a much lesser extent calprotectin - POC testing showed incremental value for SCD diagnosis beyond standard clinical information. A diagnostic strategy with routine clinical data and a POC FIT test may safely rule out SCD and prevent unnecessary endoscopy referral in approximately one third of SCD-suspected primary care patients. Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0694-3 . PMID- 27666115 TI - The design of clinical trials to support the switching and alternation of biosimilars. AB - INTRODUCTION: Loss of exclusivity for biological therapeutics opens the door for biosimilar development. Biosimilars must demonstrate structural, functional, and clinical similarity with a currently approved biological originator product. A therapeutic alternative for biologic-naive patients, a single switch from an originator to biosimilar has also been studied in clinically stable patients; further, switching therapy multiple times (alternating) between an originator and a biosimilar has been investigated. Because biosimilars are not identical to originators and no robust clinical data have convincingly demonstrated that switching or alternating therapy of stable patients is safe and efficacious, there is an imperative need to understand the characteristics of well-designed clinical trials to support these practices. Areas covered: Clinical trials of biosimilars are reviewed, with an emphasis on trial designs that incorporate therapy switching, including the NOR-SWITCH study as an example. Expert opinion: As currently designed, biosimilar clinical trials provide insufficient information to support switching or alternating between originator products and their biosimilars. Lack of regulatory guidance contributes to this void. More robust data are required to inform the safety and efficacy of switching or alternating therapies, particularly regarding immunogenicity risks. Studies that also include alternations of therapy are needed to address these knowledge gaps. PMID- 27666116 TI - Anti-proliferation effects of trifolirhizin on MKN45 cells and possible mechanism. AB - Trifolirhizin is a compound isolated from Sophora flavescens. It has been shown to exert cytotoxicity on several cancer cell lines. However, the underlying mechanism remains unknown. MKN45 cells were used as a research model. We assessed the cytotoxicity of trifolirhizin to MKN45 by MTT. Hoechst staining and TUNEL method were used to demonstrate apoptosis. Flow cytometry was used to determine cell cycle and ratio of apoptosis. Caspase activity assay was used to examine the activation of caspase cascade pathways. Western blotting was used to explore the protein levels. Consistently, trifolirhizin inhibited MKN45 xenograft tumor growth in vivo. Trifolirhizin caused a significantly decreased proliferation of MKN45 cells in a time- and dose-dependent manner, with IC50 values of 33.27+/ 2.06 ug/ml at 48 h. Western blot assay manifested that trifolirhizin activated the EGFR-MAPK signaling pathways. This study indicated that trifolirhizin may be a therapeutic application in human gastric cancer therapy. PMID- 27666117 TI - Structure and magnetic property of potassium intercalated pentacene: observation of superconducting phase in K x C22H14. AB - We report the results from systematic investigations on the structure and magnetic properties of potassium intercalated pentacene as a function of potassium content, K x C22H14 (1 ? x ? 3). Synchrotron radiation powder x-ray diffraction technique revealed that there are two different stable phases can be obtained via potassium intercalation, namely, K1C22H14 phase and K3C22H14 phase. Structural phase transition was induced when the potassium content was increased to the nominal value x = 3. This phase transition is accompanied by drastic change in their magnetic property, where those samples with compositions K1C22H14 shows ferromagnetic behavior and those with near K3C22H14 lead to observation of superconductivity with transition temperature, T c, of 4.5 K. It is first time that superconductivity was observed in linear oligoacenes. Both magnetization study and synchrotron radiation powder x-ray diffraction clearly indicates that the superconducting phase belong to K3C22H14 as a result of phase transition from triclinic to monoclinic structure induced by chemical doping. PMID- 27666118 TI - Cadmium in Chinese Postharvest Peanuts and Dietary Exposure Assessment in Associated Population. AB - Cadmium (Cd) in 8698 peanut samples collected from China in 2009-2014 was studied to evaluate its contamination level, distribution, and health risk. The average Cd concentration was 0.1684 mg kg-1; the range of 2.5-97.5% was 0.0191-0.4762 mg kg-1, indicating the cadmium-contaminated peanut level was even lower. Some peanut strains for which protein contents had a significant correlation (Pearson correlation coefficient r = 0.86**) with the Cd concentration level should be of concern. Under the same soil Cd background, the difference in Cd contents in different peanut varieties is extremely significant. For example, the Cd concentration of Silihong is about 0.4522 mg kg-1, being 7 times higher than that of Zhonghua 6. According to the exposure assessment using the probabilistic simulation method, the target hazard quotients (THQs) of all groups should be below 1. The THQ range in this study was from 0.0035 to 0.0202, suggesting that there were no potential noncinogenic effects in any group. PMID- 27666120 TI - Corrigendum: The paternal ancestry of Uttarakhand does not imitate the classical caste system of India. PMID- 27666119 TI - Prognostic and therapeutic value of mitochondrial serine hydroxyl methyltransferase 2 as a breast cancer biomarker. AB - Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (p<0.05). The clinical relevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2 protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2 mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery. PMID- 27666122 TI - Probing the Molecular Ordering and Thermal Stability of Azopolymer Layer-by-Layer Films by Second-Harmonic Generation. AB - Polyelectrolyte layer-by-layer (LbL) films have many applications, but several parameters and procedures during film fabrication determine their morphology and molecular arrangement, with important practical consequences. Here we have used optical second-harmonic generation (SHG) to investigate the molecular ordering of LbL films containing the anionic azopolymer PS-119 and the cationic polyelectrolyte PAH. We show that spontaneous drying leads to laterally homogeneous and isotropic films, while the opposite occurs for nitrogen-flow drying. The effect of film thickness and pH of the assembling/rinsing solutions on the molecular ordering was also investigated. The optical nonlinearity tends to significantly decrease for thicker films (~10 bilayers), and a slight alternation of SHG intensity for films with odd or even number of layers (complete vs incomplete bilayers) was also observed, which results from the reorientation of azopolymer groups in the last layer after adsorption of an additional PAH layer. We propose a qualitative electrostatic model to explain the pH dependence of film growth and azopolymer orientation, which is based on changes of the charge density of the substrate and PAH and on different ionic screening of electrostatic interactions at various pH values. We also found that the nonlinear response presents a gradual and significant reduction upon heating, which is inconsistent with a glass transition temperature for these ultrathin LbL films. The thermal stability is improved with a combination of low ionic strength and higher charge density of the polyelectrolytes and substrate, which promotes better interlayer complexation. The SHG signal is recovered upon cooling, although for some conditions the molecular arrangement became anisotropic after a heating/cooling cycle. Such detailed information about the structural order of thin nonlinear optical azopolymer LbL films demonstrates that SHG is a powerful technique to probe the film structure at the molecular level, with important consequences for their applications in optical devices. PMID- 27666123 TI - Lasers for caries removal in deciduous and permanent teeth. AB - BACKGROUND: Despite considerable improvements in oral health, dental caries continue to be a public health issue. The most frequently used, and universally accepted technique, to remove caries is through mechanical ablation of decayed tissues by means of rotating drills (diamond or tungsten carbide, or both). In the past few decades, the introduction of adhesive filling materials (resin composites) has affected cavity filling procedures by reducing its retention needs, with advantages for dental tissue conservation. Consequently, new minimally invasive strategies were introduced into dental practice, such as the use of lasers to perform highly controlled tissue ablation. Laser use has also raised expectations of limiting pain and discomfort compared to using drills, as well as overcoming drill phobia. OBJECTIVES: The main objective of the review was to compare the effects of laser-based methods to conventional mechanical methods for removing dental caries in deciduous and permanent teeth. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (searched 22 June 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5) in the Cochrane Library (searched 22 June 2016), MEDLINE Ovid (1946 to 22 June 2016), Embase Ovid (1980 to 22 June 2016), ProQuest Dissertations and Theses (1980 to 22 June 2016), Zetoc (limited to conference proceedings) (1993 to 22 June 2016), and ISI Web of Knowledge (limited to conference proceedings) (1990 to 22 June 2016). We checked the reference lists of relevant articles to identify additional studies. We searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. SELECTION CRITERIA: We included randomised controlled trials, split-mouth trials and cluster-randomised trials (irrespective of their language) comparing laser therapy to drill ablation of caries. We included participants of any age (children, adolescents and adults). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of citations identified by the review search strategy. Two review authors independently evaluated the full text of relevant primary studies, assessed risk of bias and extracted data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included nine randomised trials, published between 1998 and 2014, involving 662 participants. The population consisted of both children and adolescents in four trials, only adults in four trials, and both children/adolescents and adults in one trial. Four studies examined only permanent teeth, and five studies evaluated both deciduous and permanent teeth. Six trials used Er:YAG (erbium-doped yttrium aluminium garnet) lasers, two trials employed Er,Cr:YSGG (erbium, chromium: yttrium-scandium-gallium-garnet) lasers, and one trial used Nd:YAG (neodymium doped yttrium aluminium garnet) laser.Overall, the trials had small sample sizes, and the majority were at unclear or high risk of bias. The primary outcomes were evaluated in a limited number of trials (removal of caries (four trials (but only two reported quantitative data)); episodes of pain (five studies)). There was insufficient evidence to suggest that either lasers or drill were better at caries removal (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.99 to 1.01; 2 studies; 256 treated caries; P = 0.75; I2 = 0%; low-quality evidence).The incidence of moderate or high pain was greater in the drill group compared to the laser group (RR 0.40, 95% CI 0.28 to 0.57; 2 studies; 143 participants; P < 0.001; I2 = 50%). Similarly, the need for anaesthesia was significantly higher in the drill group than in the laser group (RR 0.25, 95% CI 0.10 to 0.65; 3 studies; 217 children/adolescents; P = 0.004; I2 = 0%).In terms of marginal integrity of restoration, there was no evidence of a difference between laser and drill comparisons evaluated at 6 months (RR 1.00, 95% CI 0.21 to 4.78; 3 studies), 1 year (RR 1.59, 95% CI 0.34 to 7.38; 2 studies), or 2 years (RR 1.00, 95% CI 0.21 to 4.74; 1 study).There was no evidence of a difference for durability of restoration between laser therapy or drill at 6 months' follow-up (RR 2.40, 95% CI 0.65 to 8.77; 4 studies), at 1 year (RR 1.40, 95% CI 0.29 to 6.78; 2 studies) or at 2 years' follow-up (RR 0.50, 95% CI 0.02 to 14.60; 1 study).Only two trials investigated the recurrence of caries, but no events occurred during 6 months' follow-up.There was insufficient evidence of a difference between laser or drill in terms of pulpal inflammation or necrosis at 1 week (RR 1.51, 95% CI 0.26 to 8.75; 3 studies) and at 6 months (RR 0.99, 95% CI 0.10 to 9.41; 2 studies). AUTHORS' CONCLUSIONS: Given the low quality of the body of evidence, we concluded that evidence was insufficient to support the use of laser as an alternative to traditional drill therapy for caries removal. We found some evidence in favour of laser therapy for pain control, need of anaesthesia and patient discomfort, but, again, the body of evidence was of low quality. Additional well-designed, randomised trials investigating the most relevant outcomes are needed. PMID- 27666121 TI - Enzyme Catalysis To Power Micro/Nanomachines. AB - Enzymes play a crucial role in many biological processes which require harnessing and converting free chemical energy into kinetic forces in order to accomplish tasks. Enzymes are considered to be molecular machines, not only because of their capability of energy conversion in biological systems but also because enzymatic catalysis can result in enhanced diffusion of enzymes at a molecular level. Enlightened by nature's design of biological machinery, researchers have investigated various types of synthetic micro/nanomachines by using enzymatic reactions to achieve self-propulsion of micro/nanoarchitectures. Yet, the mechanism of motion is still under debate in current literature. Versatile proof of-concept applications of these enzyme-powered micro/nanodevices have been recently demonstrated. In this review, we focus on discussing enzymes not only as stochastic swimmers but also as nanoengines to power self-propelled synthetic motors. We present an overview on different enzyme-powered micro/nanomachines, the current debate on their motion mechanism, methods to provide motion and speed control, and an outlook of the future potentials of this multidisciplinary field. PMID- 27666124 TI - miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1. AB - Crizotinib is an orally administered drug for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non small cell lung cancer (NSCLC). Despite the impressive efficacy of crizotinib in the treatment of ALK-positive lung cancer, acquired resistance eventually develops in the majority of patients. The microRNA (miR)-200c reverses the resistance of lung cancer cells to various chemotherapeutic drugs and molecular targeted drugs, however, whether it can reverse the resistance of crizotinib remains unknown. The present study established a crizotinib resistant cell line (NCI-2228/CRI), which was derived from the parental NCI-2228 cell line by long term exposure to increasing concentrations of crizotinib. Through overexpression and suppression of miR-200c expression, the characteristics associated with epithelial-mesenchymal transition (EMT), including morphology, EMT marker proteins and cellular mobility, were investigated. Cell viability and invasion assays demonstrated that high expression of miR-200c significantly inhibited the proliferation, migration and invasion of NCI-2228 cells compared with the negative control. A luciferase reporter assay indicated that miR-200c directly targeted the 3'-untranslated region of zinc finger E-box binding homeobox 1. Additionally, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that the mRNA levels of N-cadherin and Vimentin were decreased in NCI-2228 cells transfected with miR-200c mimic compared with negative control cells, whereas the mRNA level of E-cadherin was increased. In addition, EMT was reversed by miR-200c, which suggests that miR-200c may serve a role in mediating the sensitivity of NCI-2228/CRI cells to crizotinib. The present study may therefore contribute to improving the sensitivity of ALK positive lung cancer cells to crizotinib. PMID- 27666125 TI - Prospects of electrochemical immunosensors for early diagnosis of preeclampsia. AB - Preeclampsia is a vascular multisystem disorder that accounts for varying degree of morbidity and mortality of mother and the fetus. This can be significantly averted if diagnosed at an early (18-20 weeks) stage of gestation, as there is no known way to prevent preeclampsia. In spite of extensive work on biomarker discovery, the existing method for its detection is mostly based on colorimetric immunoassays whose sensitivity is ranging in nanomolar range. Further, it has also been observed that change in the expression of a single biomarker is not sufficient to diagnose this condition. So, for early diagnosis (by 18-20 weeks), an immuno-diagnostic platform with detection limits in picomolar range and beyond along with the ability to do simultaneous detection of multiple analyte would be of great importance. A nano-immunosensors with an electrochemical readout system can be a potential alternative that promises for the ultrasensitive detection of analyte with high specificity as well as suitability for on-site analysis. Coupling the lateral flow technology with immunosensors would make it feasible to detect more than one biomarker simultaneously on a microchip. This review intends to summarize the potential preeclampsia biomarkers, limitations of existing diagnostic methods along with the recent advancements, and prospects to develop electrochemical immunosensors for early clinical diagnosis. PMID- 27666127 TI - Perioperative beta-Blockade in Noncardiac Surgery: A Cautionary Tale of Over reliance on Small Randomized Prospective Trials. AB - PURPOSE: Our aim was to analyze the current scientific literature relevant to the use of beta-adrenergic receptor antagonists for the prevention of cardiovascular morbidity and mortality in patients undergoing noncardiac surgery. METHODS: A PubMed search was conducted for the following concepts: pre- or perioperative, beta-adrenergic receptor antagonist, treatment outcome, and cardiovascular complication. Randomized clinical trials measuring the effect of beta-adrenergic blocking agents against that of placebo on cardiovascular outcomes after noncardiac surgery were included in the review. FINDINGS: Two small randomized controlled trials published in 1996 and 1999 reported associations between perioperative beta-blockade and significant reductions in long-term and 30-day cardiac mortality, respectively. These 2 studies prompted guideline changes in 2002 encouraging perioperative beta-blockade in subsets of noncardiac surgery patients. However, subsequent trials failed to validate these results. In 2008, the first large randomized controlled trial on the topic was published and found an association between perioperative beta-blockade and an increase in perioperative mortality. Furthermore, in 2011, the lead author of the 1999 study was dismissed from his academic position for scientific misconduct, casting doubt on the validity of guidelines based on his work. Existing studies are highly heterogeneous, making comparisons difficult. Current literature does not support initiating perioperative beta-blockade in noncardiac surgery patients not already receiving these medications. IMPLICATIONS: Future research on the topic should account for the influence individual genetic variation can have on outcomes and beta-blocker metabolism. Additionally, the relationship between outcomes and the beta-1 selectivity of different beta-blockers should be explored. PMID- 27666126 TI - Acute Pharmacodynamic Effects of Empagliflozin With and Without Diuretic Agents in Patients With Type 2 Diabetes Mellitus. AB - PURPOSE: The goal of this study was to investigate the pharmacodynamic effects of co-administration of empagliflozin, a sodium glucose cotransporter 2 inhibitor, with diuretic agents. METHODS: In a randomized, open-label cross-over study, 22 patients with type 2 diabetes mellitus received empagliflozin 25 mg for 5 days and either hydrochlorothiazide 25 mg for 4 days followed by hydrochlorothiazide 25 mg plus empagliflozin 25 mg for 5 days, or torasemide 5 mg for 4 days followed by torasemide 5 mg plus empagliflozin 25 mg for 5 days; 20 completed treatment. Food, fluid, and sodium intake were standardized for 3 days before and during treatment. FINDINGS: At baseline, the median age of the treated patients was 56 years (range, 40-65 years), body mass index was 26.8 kg/m2 (range, 20.1-34.4 kg/m2), fasting plasma glucose was 8.6 mmol/L (range, 6.0-12.9 mmol/L), and glycosylated hemoglobin level was 7.6% (range, 7%-10%). Empagliflozin significantly increased 24-hour urinary glucose excretion and reduced fasting serum glucose levels. These effects were maintained after co-administration with either diuretic. Urinary sodium excretion did not significantly change with empagliflozin or diuretic administration alone, but seemed to increase compared with either diuretic alone when empagliflozin was co-administered with either diuretic. Plasma renin and serum aldosterone levels were unaltered with empagliflozin or torasemide alone, but tended to increase with hydrochlorothiazide alone, and tended to increase when empagliflozin was co administered with a diuretic compared with either diuretic alone. Urinary volume did not increase with empagliflozin or diuretics alone, but increased when empagliflozin was co-administered with either diuretic. IMPLICATIONS: Empagliflozin alone for 5 days increased urinary glucose excretion but did not seem to have a relevant impact on urine volume or electrolytes. When empagliflozin was co-administered with a diuretic agent, urinary glucose excretion remained increased, and the renin-angiotensin system was activated. Clinicaltrials.gov identifier: NCT01276288. PMID- 27666128 TI - Difference between Extra- and Intracellular T1 Values of Carboxylic Acids Affects the Quantitative Analysis of Cellular Kinetics by Hyperpolarized NMR. AB - Incomplete knowledge of the longitudinal relaxation time constant (T1 ) leads to incorrect assumptions in quantitative kinetic models of cellular systems, studied by hyperpolarized real-time NMR. Using an assay that measures the intracellular signal of small carboxylic acids in living cells, the intracellular T1 of the carboxylic acid moiety of acetate, keto-isocaproate, pyruvate, and butyrate was determined. The intracellular T1 is shown to be up to four-fold shorter than the extracellular T1 . Such a large difference in T1 values between the inside and the outside of the cell has significant influence on the quantification of intracellular metabolic activity. It is expected that the significantly shorter T1 value of the carboxylic moieties inside cells is a result of macromolecular crowding. An artificial cytosol has been prepared and applied to predict the T1 of other carboxylic acids. We demonstrate the value of this prediction tool. PMID- 27666129 TI - Using a qualitative approach to conceptualize concerns of patients with neurofibromatosis type 1 associated plexiform neurofibromas (pNF) across the lifespan. AB - Neurofibromatosis Type 1 (NF1) plexiform neurofibromas (pNFs) are associated with a variety of symptoms and concerns that affect patients' quality of life (QOL), highlighting the value of incorporating the patients' perspective when evaluating treatment outcomes. To better conceptualize the experience of patients with pNFs, this qualitative study sought to identify the most important outcomes to assess from the perspective of patients, families, and clinicians. Clinicians, patients age 5 years old and above, and parents of patients aged 5-17 years participated in semi-structured interviews to elicit the pNF symptoms/concerns considered most important to assess. The data were analyzed using an iterative coding procedure and the frequency with which symptoms/concerns emerged was tabulated. Eight clinicians, 31 patients, and 17 parents of patients participated in semi structured interviews. The most frequently reported concerns raised by patients across all age groups included pain, appearance/disfigurement, social activity/role participation, stigma, and anxiety. For parents, physical functioning was the primary concern, followed by pain, social activity/role participation, appearance/disfigurement, and social relationships. The resulting conceptual framework included five domains to represent the most important identified symptoms/concerns: pain, social functioning, physical function impact, stigma, and emotional distress. This conceptual framework describing the symptoms/concerns of patients with pNF can help investigators create a measurement system to improve assessment of aspects of QOL only patients can report on. It may also provide the ability to identify symptoms/concerns that might warrant referrals to various clinical disciplines. (c) 2016 Wiley Periodicals, Inc. PMID- 27666130 TI - Metastatic breast carcinoma in pleural fluid: Correlation of receptor and HER2 status with the primary carcinoma-a pilot study. AB - BACKGROUND: Documenting the four molecular subtypes of breast carcinoma is significant as they determine response to therapy, disease free interval and survival. Our aim was to document the subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2): namely ER + PR+ HER2+; ER + PR + HER2 ; ER-PR-HER2+; and ER-PR-HER2- in metastatic breast carcinoma in pleural fluid and compare them with their expression in the primary breast tumor. METHODS: Over a period of 18 months, 13 cases of invasive breast carcinoma with metastases to the pleural cavity were studied for subtypes. ER, PR, and HER2 were determined by IHC in the primary breast tumor and the cell blocks of the pleural fluid with metastatic carcinoma. RESULTS: Age ranged from 33 to 75 years. The primary tumor was ER + PR + HER2+; ER + PR + HER2-; ER-PR-HER2+ and ER-PR-HER2- in 2,9,0 and two cases, respectively while the metastatic tumor in pleural fluid was ER + PR + HER2+; ER + PR + HER2-; ER-PR- HER2+ and ER-PR-HER2- in 6, 3, 3, and 1, respectively. In five cases there was complete correlation between the primary and metastatic tumor. In 7 cases with HER2- primary tumor the metastases was HER2+. One from ER + PR+ HER2- primary tumor showed triple negative expression in the metastasis. CONCLUSIONS: Determining the molecular subtype in metastatic breast carcinoma is of importance as it affects the management. In our series 63% of metastatic tumors to the pleural fluid became HER2 positive and would thus require appropriate therapy. Diagn. Cytopathol. 2016;44:980-986. (c) 2016 Wiley Periodicals, Inc. PMID- 27666132 TI - Topical phenothrin treatment in a case of crusted scabies with nail involvement. PMID- 27666131 TI - Postoperative seizure control in patients with tumor-associated epilepsy. AB - OBJECTIVE: The patterns of postoperative seizure control and response to antiepileptic drugs (AEDs) in tumor-associated epilepsy (TAE) are poorly understood. We aim to document these characteristics in patients with supratentorial gliomas. METHODS: This was a retrospective analysis of 186 patients with supratentorial gliomas. Seizure patterns were classified into four groups: A, no postoperative seizure; B, early postoperative seizure control within 6 months; C, fluctuating seizure control; and D, never seizure-free. Rates and duration of seizure freedom, subsequent seizure relapse, and response to AED were analyzed. RESULTS: Among patients included, 49 (26.3%) had grade II, 28 (15.1%) had grade III, and 109 (58.6%) had grade IV glioma. Outcome pattern A was observed in 95 (51.1%), B in 22 (11.8%), C in 45 (24.2%), and D in 24 (12.9%). One hundred nineteen patients had at least one seizure and were classified as having TAE. Compared to pattern A, pattern B was predicted by histologic progression; pattern C by tumor grade, preoperative seizure, and histologic progression, and pattern D by preoperative seizure and gross total resection. Among patients with TAE, 57.5% of grade II, 68.2% of grade III, and 26.3% of grade IV experienced a period of 12-month seizure freedom. After first 12-month seizure remission, 39.1%, 60.0%, and 13.3% of grade II, III, and IV gliomas, respectively, experienced subsequent seizure; 22.6% of those with TAE reached terminal seizure freedom of at least 12 months on their first postoperative AED regimen, 6.5% on their second regimen, and 5.4% on subsequent regimens. SIGNIFICANCE: Distinct patterns of postoperative seizure control exist in gliomas; they have specific risk factor profiles, and we hypothesize these correspond to unique pathogenic mechanisms. Twelve-month seizure freedom with subsequent relapse is frequent in grade II-III gliomas. Response to AEDs is markedly poorer than with non-TAE, highlighting the complex epileptogenicity of gliomas. PMID- 27666134 TI - The Work of Inscription: Antenatal Care, Birth Documents, and Shan Migrant Women in Chiang Mai. AB - For transnational migrant populations, securing birth documents of newly born children has crucial importance in avoiding statelessness for new generations. Drawing on discussions of sovereignty and political subjectivization, I ask how the fact of birth is constituted in the context of transnational migration. Based on ethnographic data collected from an antenatal clinic in Thailand, this article describes how Shan migrant women from Myanmar (also known as Burma) utilize reproductive health services as a way of assuring a safe birth while acquiring identification documents. Paying close attention to technologies of inscription adopted for maternal care and birth registration, I argue that enacting bureaucratic documents offers a chance for migrant women to bridge the interstice between human and citizen. Birth certificates for migrant children, while embodying legal ambiguity and uncertainty, epitomize non-citizen subjects' assertion of their political relationship with the state. PMID- 27666133 TI - Palaeobiology of Hyaenodon exiguus (Hyaenodonta, Mammalia) based on morphometric analysis of the bony labyrinth. AB - Species of the extinct genus Hyaenodon were among the largest carnivorous mammals from the Late Eocene through Early Miocene in North America, Europe and Asia. The origin, phylogeny and palaeobiology of Hyaenodonta are still ambiguous. Most previous studies focused on teeth and dental function in these highly adapted species, which might be influenced by convergent morphologies. The anatomy of the bony labyrinth in vertebrates is generally quite conservative and, additionally, was used in functional-morphological studies. This study provides the first anatomical description of the bony labyrinth of the extinct European species Hyaenodon exiguus in comparison to selected extant carnivoran taxa discussed from a functional-morphological perspective. Hyaenodon exiguus may have occupied a hyaena-like dietary niche with a semi-arboreal lifestyle, based on the relative height, width and length of the semicircular canals of the inner ear. However, this contradicts previous functional-morphological studies focusing on the diameter of the canals, which presumably represent the signal of locomotion mode. PMID- 27666135 TI - Rapid synthesis of flavone-based monoamine oxidase (MAO) inhibitors targeting two active sites using click chemistry. AB - A new library of flavone derivatives targeting two active sites of monoamine oxidases ("aromatic cage" and substrate cavity) were designed and synthesized using click chemistry (CuAAC reaction) between 6-N3 -2-phenyl chromones (Az1-Az2) and a series of alkynes (k1-k20). Their inhibitory activities against MAO isoforms (MAO-A and MAO-B) are evaluated. Compounds with fluorine, amide bonds, or amino bonds have shown better inhibition. The most potent flavone MAO inhibitor studied is Az2k19 (1.6 MUm for MAO-A, 2.1 MUm for MAO-B), while Az1k15 and Az2k15 displayed better selectivity toward MAO-B (SI > 10). Docking studies are in accordance with our hypothesis that these inhibitors are most likely located at both the substrate cavity and the "aromatic cage". Our results show that it is considerable to develop new MAO inhibitors from C6 substitution of flavone derivatives and that these compounds are also potential for the treatment of diseases associated with MAOs. PMID- 27666136 TI - Microvascular reactivity and endothelial glycocalyx degradation when administering hydroxyethyl starch or crystalloid during off-pump coronary artery bypass graft surgery: a randomised trial. AB - The infusion of fluids to patients may affect tissue microcirculation and the endothelial glycocalyx. However, the effects of hydroxyethyl starch and crystalloid on endothelial glycocalyx degradation and microvascular reactivity have not been evaluated in detail. We hypothesised that hydroxyethyl starch may cause less endothelial glycocalyx degradation and better microvascular reactivity than that caused by crystalloid. We randomly allocated 120 patients undergoing off-pump coronary artery bypass graft surgery to receive up to 20 ml.kg-1 of either hydroxyethyl starch 670/0.75 or crystalloid for intra-operative fluid resuscitation. Crystalloid was then infused to meet ongoing fluid requirements. During the peri-operative period, vascular occlusion tests were performed to assess microvascular reactivity, and serum syndecan-1 was measured as an index of endothelial glycocalyx degradation. The median (IQR [range]) fluid infused during surgery was significantly less in the hydroxyethyl starch group than the crystalloid group; 2800 (2150-3550 [1400-7300]) vs. 3925 (3100-4725 [1900-6700]) ml, respectively, p < 0.001. Vascular occlusion test parameters, including tissue oxygen saturation, occlusion and recovery slope did not differ significantly between the groups. Peri-operative changes in syndecan-1 were not significantly different between the groups. We conclude that, in patients undergoing off-pump coronary artery bypass graft surgery, compared with crystalloid, the use of hydroxyethyl starch 670/0.75 did not result in significant differences in microvascular reactivity or endothelial glycocalyx degradation. PMID- 27666137 TI - Cost-effectiveness, in a randomized trial, of glass-ionomer-based and resin sealant materials after 4 yr. AB - This study, conducted from a government program perspective, compared the incremental cost-effectiveness of oral health interventions, in particular their delivery to underserved populations in whom dental sealants constitute an important, high-yielding complement to toothbrushing in dental-caries prevention. The study data concern the relative cost-effectiveness of three sealant materials in four approaches to prevent cavitated dentine carious lesions in permanent molars in a community intervention trial among school-age children in Wuhan, China. The four approaches were high-viscosity glass-ionomer cement without heat application (HVGIC); high-viscosity glass-ionomer cement with heat application [light-emitting diode (LED) thermocured HVGIC]; glass-carbomer; and composite resin. The costs studied were: cost of sealing permanent molars; adverse event costs for restoring cavitated dentine carious lesions developing within 4 yr in study data; and projections of 1,000 sealants per group. Preventing one more cavitated dentine carious lesion cost US$105 for the study data when comparing HVGIC (n = 405) with composite resin (n = 396) and US$59 per 1,000 sealants in the projections; LED thermocured HVGIC compared with composite resin cost US$115 for one more cavitated lesion and US$52 per 1,000 sealants, respectively. Although more expensive than composite resin, LED thermocured HVGIC was identified as the most cost-effective among the sealant materials studied. Ease of application, minimal technical and infrastructure requirements, and cost effectiveness make glass-ionomers a practicable option for governments making decisions under economic constraints. PMID- 27666139 TI - Celecoxib enhances the inhibitory effect of 5-FU on human squamous cell carcinoma proliferation by ROS production. AB - OBJECTIVES: The role of celecoxib in preventing and treating tumors has attracted broad attention in recent years because of its selective and specific inhibition of COX-2 activity. We investigated the inhibitory effects and mechanisms of celecoxib combined with 5-fluorouracil (5-FU) on proliferation of squamous cell carcinoma cells in vivo and in vitro. STUDY DESIGN: Animal study and basic research. METHODS: SNU-1041 and SNU-1076 squamous cell lines and an orthotopic tongue cancer mouse model were used to study growth inhibition with 5-FU enhanced by celecoxib. Sensitivity of cells to drug treatment was analyzed by the MTT assay, and generation of reactive oxygen species (ROS) was measured using dichlorofluorescein diacetate. Phosphorylation of AKT was detected by Western blotting. Survival analysis in the mouse model was assessed according to combination treatment with 5-FU and celecoxib. RESULTS: Reactive oxygen species production in vitro was highest when celecoxib was administered 48 hours after 5 FU treatment. 5-FU-induced inhibition of cell proliferation was enhanced when combined with celecoxib, which was positively correlated with ROS production. Antioxidant treatment reversed 5-FU-inhibited cell proliferation by up to 60%. Cotreatment with celecoxib and 5-FU partially blocked AKT phosphorylation, although no significant changes in total AKT protein levels were detected. An increased survival time was observed in an orthotopic mouse model treated with a combination of celecoxib and 5-FU compared to treatment with either agent alone. CONCLUSION: Celecoxib may have an enhanced anticancer effect in combination with 5-FU. Reactive oxygen species production may be a key mechanism in this combination therapy by inhibiting the AKT pathway. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:E117-E123, 2017. PMID- 27666138 TI - D2-resected stage IIIc gastric cancer patients benefit from adjuvant chemoradiotherapy. AB - Although adjuvant chemoradiotherapy has been an important part in the treatment of gastric cancer, whether or not adjuvant radiation can benefit patients undergoing resection with D2 lymph node dissection remains controversial. This retrospective study aimed to evaluate the role of adjuvant chemoradiotherapy on patients with D2-resected gastric cancer. A total of 337 patients with resected gastric cancer treated at Zhongnan Hospital of Wuhan University from 2004 to 2012 were retrospectively analyzed. Eligible patients were divided into the adjuvant chemoradiotherapy group (CRT; n = 124) and the adjuvant chemotherapy group (CT; n = 213). The primary endpoints were disease-free survival (DFS) and overall survival (OS), with toxicity as the secondary endpoint. A subgroup analysis was performed based on clinical staging. The two groups were comparable in baseline characteristic, except for the number of lymph nodes dissected. The median OSs in the CRT and CT groups were 51.0 months and 48.6 months, respectively (P = 0.251), and the median DFSs were 40.7 months and 31.2 months, respectively (P = 0.112). Subgroup analysis revealed that the median OSs in patients at stage IIIc in the CRT group and CT group were 29.0 and 23.0 months, respectively (P = 0.049), and those of the median DFSs were 21.2 and 15.1 months, respectively (P = 0.015). There was no significant difference in main adverse events between two groups. Collectively, adjuvant chemoradiotherapy in gastric cancer patients with D2 resection was well tolerated. For Stage IIIc patients, the addition of adjuvant chemoradiotherapy was associated with a significant benefit in both OS and DFS. PMID- 27666140 TI - The new intra-articular calcaneal fracture classification system in term of sustentacular fragment configurations and incorporation of posterior calcaneal facet fractures with fracture components of the calcaneal body. AB - OBJECTIVE: The aim of this study was to develop a new calcaneal fracture classification system which will consider sustentacular fragment configuration and relation of posterior calcaneal facet to calcaneal body. METHODS: The new classification system used sustentacular fragment configuration and relation of posterior calcaneal facet fracture with fracture components of calcaneal body as key aspects of main types and subtypes. Between 2000 and 2014, 126 intraarticular calcaneal fractures were classified according to the new classification system by using computed tomography images. The new classification system was studied in term of reliability, correlation to choices of treatment, implant fixation and quality of fracture reduction. RESULTS: Types of sustentacular fragment comprised type A, B and C. Type A sustentacular fragment included sustentacular tali containing middle calcaneal facet. In Type B and C fractures sustentacular fragment included medial aspect and entire posterior calcaneal facet as a single unit, respectively. The fractures with type A, B and C sustentacular fragments were classified as main type A, B and C intra-articular calcaneal fractures. The main type A and B comprised 4 subtypes. Subtypes A1, A3, B1, and B3 associated with avulsion and bending fragments of calcaneal body. Subtype A2, B2, and B4 associated with burst calcaneal body. Subtype B4 was not found in the study. Main type C had no subtype and associated with burst calcaneal body. The data showed good reliability. CONCLUSION: The study showed that our new intra-articular calcaneal fracture classification system correlates to choices of treatment, implant fixation and quality of fracture reduction. LEVEL OF EVIDENCE: Level IV, Study of Diagnostic Test. PMID- 27666142 TI - Response to letter to the Editor re 'Surgery in Disorders of Sex Development (DSD) with a gender issue: If (why), when and how?' PMID- 27666141 TI - Iatrogenic lateral meniscus anterior horn injury in different tibial tunnel placement techniques in ACL reconstruction surgery - A cadaveric study. AB - OBJECTIVES: The aim of this study was to analyze the effect of tibial tunnel positioning in single bundle and double bundle ACL reconstructions on lateral meniscus anterior root. MATERIALS: Twelve single knee cadavers were used, 6 for a single bundle ACL reconstruction, which were reamed gradually starting from 8 mm, 9 mm and ended with a 10 mm reamers, while the other 6 were prepared for a double bundle ACL reconstruction in which 7 mm reamer for the AM tunnel and 6 mm reamer for the PL tunnel were used. After drilling, changes of lengths and thicknesses of anterior horns of the lateral menisci were recorded. RESULTS: Before drilling, the groups were homogenous for the lateral menisci dimensions. After drilling, no statistically significant difference was noticed between the two groups. However, in single bundle group, 2 anterior horns width injury (1.44 mm and 2.13 mm) with the 9 mm reamer and 3 anterior horns width injury (2.51 mm, 3.55 mm and 4.28 mm) with the 10 mm reamer were recorded. However in double bundle group a single anterior horn width injury (2.82 mm) was recorded. CONCLUSION: Using a greater size reamer in single bundle reconstruction, causes a relatively higher risk of lateral meniscal anterior root injury. Lateral meniscus stability should be examined arthroscopically after reaming with large reamers. PMID- 27666143 TI - Re: "Laparoscopic transposition of lower-pole crossing vessels: Long-term follow up of 33 patients at puberty". PMID- 27666145 TI - Understanding the Subtleties of Frustrated Lewis Pair Activation of Carbonyl Compounds by N-Heterocyclic Carbene/Alkyl Gallium Pairings. AB - This study reports the use of the trisalkylgallium GaR3 (R=CH2 SiMe3 ), containing sterically demanding monosilyl groups, as an effective Lewis-acid component for frustrated Lewis pair activation of carbonyl compounds, when combined with the bulky N-heterocyclic carbene 1,3-bis(tert-butyl)imidazol-2 ylidene (ItBu) or 1,3-bis(tert-butyl)imidazolin-2-ylidene (SItBu). The reduction of aldehydes can be achieved by insertion into the C=O functionality at the C2 (so-called normal) position of the carbene affording zwitterionic products [ItBuCH2 OGaR3 ] (1) or [ItBuCH(p-Br-C6 H4 )OGaR3 ] (2), or alternatively, at its abnormal (C4) site yielding [aItBuCH(p-Br-C6 H4 )OGaR3 ] (3). As evidence of the cooperative behaviour of both components, ItBu and GaR3 , neither of them alone are able to activate any of the carbonyl-containing substrates included in this study NMR spectroscopic studies of the new compounds point to complex equilibria involving the formation of kinetic and thermodynamic species as implicated through DFT calculations. Extension to ketones proved successful for electrophilic alpha,alpha,alpha-trifluoroacetophenone, yielding [aItBuC(Ph)(CF3 )OGaR3 ] (7). However, in the case of ketones and nitriles bearing acidic hydrogen atoms, C-H bond activation takes place preferentially, affording novel imidazolium gallate salts such as [{ItBuH}+ {(p-I-C6 H4 )C(CH2 )OGaR3 }- ] (8) or [{ItBuH}+ {Ph2 C=C=NGaR3 }- ] (12). PMID- 27666144 TI - Reliability of grading of vesicoureteral reflux and other findings on voiding cystourethrography. AB - INTRODUCTION: Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings. OBJECTIVE: To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR. STUDY DESIGN: The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability. RESULTS: Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (>=92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases. DISCUSSION: Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG. CONCLUSION: The considerable inter observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR. PMID- 27666147 TI - Parental involvement in neonatal critical care decision-making. AB - The article analyses the decision-making process between doctors and parents of babies in neonatal intensive care. In particular, it focuses on cases in which the decision concerns the redirection of care from full intensive care to palliative care at the end of life. Thirty one families were recruited from a neonatal intensive care unit in England and their formal interactions with the doctor recorded. The conversations were transcribed and analysed using conversation analysis. Analysis focused on sequences in which decisions about the redirection of care were initiated and progressed. Two distinct communicative approaches to decision-making were used by doctors: 'making recommendations' and 'providing options'. Different trajectories for parental involvement in decision making were afforded by each design, as well as differences in terms of the alignments, or conflicts, between doctors and parents. 'Making recommendations' led to misalignment and reduced opportunities for questions and collaboration; 'providing options' led to an aligned approach with opportunities for questions and fuller participation in the decision-making process. The findings are discussed in the context of clinical uncertainty, moral responsibility and the implications for medical communication training and guidance. A Virtual Abstract of this paper can be accessed at: https://www.youtube.com/watch?v=MyuymxDNupk&feature=youtu.be. PMID- 27666146 TI - Dimension-Based Statistical Learning Affects Both Speech Perception and Production. AB - Multiple acoustic dimensions signal speech categories. However, dimensions vary in their informativeness; some are more diagnostic of category membership than others. Speech categorization reflects these dimensional regularities such that diagnostic dimensions carry more "perceptual weight" and more effectively signal category membership to native listeners. Yet perceptual weights are malleable. When short-term experience deviates from long-term language norms, such as in a foreign accent, the perceptual weight of acoustic dimensions in signaling speech category membership rapidly adjusts. The present study investigated whether rapid adjustments in listeners' perceptual weights in response to speech that deviates from the norms also affects listeners' own speech productions. In a word recognition task, the correlation between two acoustic dimensions signaling consonant categories, fundamental frequency (F0) and voice onset time (VOT), matched the correlation typical of English, and then shifted to an "artificial accent" that reversed the relationship, and then shifted back. Brief, incidental exposure to the artificial accent caused participants to down-weight perceptual reliance on F0, consistent with previous research. Throughout the task, participants were intermittently prompted with pictures to produce these same words. In the block in which listeners heard the artificial accent with a reversed F0 * VOT correlation, F0 was a less robust cue to voicing in listeners' own speech productions. The statistical regularities of short-term speech input affect both speech perception and production, as evidenced via shifts in how acoustic dimensions are weighted. PMID- 27666148 TI - Using gamification to develop academic writing skills in dental undergraduate students. AB - OBJECTIVES: To assess the satisfaction of first-year dental students with gamification and its effect on perceived and actual improvement of academic writing. METHODS: Two first-year classes of dental undergraduate students were recruited for the study which extended over 4 months and ended in January 2015. A pre-intervention assessment of students' academic writing skills was performed using criteria to evaluate writing. The same criteria were used to evaluate the final writing assignment after the intervention. Students' satisfaction with game aspects was assessed. The per cent change in writing score was regressed on scores of satisfaction with game aspects controlling for gender. Perceived improvement in writing was also assessed. RESULTS: Data from 87 (94.6%) students were available for analysis. Students' overall satisfaction with the gamified experience was modest [mean (SD) = 5.9 (2.1)] and so was their overall perception of improvement in writing [mean (SD) = 6.0 (2.2)]. The per cent score of the first assignment was 35.6 which improved to 80 in the last assignment. Satisfaction with playing the game was significantly associated with higher percentage of improvement in actual writing skills [regression coefficient (95% confidence interval) = 21.1 (1.9, 40.2)]. CONCLUSION: Using gamification in an obligatory course for first-year dental students was associated with an improvement in academic writing skills although students' satisfaction with game aspects was modest and their willingness to use gamification in future courses was minimal. PMID- 27666149 TI - Fixed 50:50 mixture of nitrous oxide and oxygen to reduce lumbar-puncture-induced pain: a randomized controlled trial. AB - BACKGROUND AND PURPOSE: Lumbar puncture (LP) has been frequently performed for more than a century. This procedure is still stressful and often painful. The aim of the study was to evaluate the efficacy of a fixed 50% nitrous oxide-oxygen mixture compared to placebo to reduce immediate procedural pain and anxiety during LP. METHODS: A randomized controlled trial was conducted involving adults who needed a cerebrospinal fluid analysis. Patients were randomly assigned to inhale either a fixed 50% nitrous oxide-oxygen mixture (50% N2 O-O2 ) or medical air (22% O2 -78% N2 ). Cutaneous application of a eutectic mixture of local anaesthetics was systematically done and all LPs were performed with pencil point 25G needles (20G introducer needle). The primary end-point was the maximal pain level felt by the patient during the procedure, the maximal anxiety level being a secondary outcome, both measured using a numerical rating scale (0-10). RESULTS: A total of 66 consecutive patients were randomized. The analysis was intention to treat. The maximal pain was 4.9 +/- 2.7 for the 33 patients receiving air and 2.7 +/- 2.7 for the 33 receiving 50% N2 O-O2 (P = 0.002). Similarly, the maximal LP induced anxiety was 4.5 +/- 3.1 vs. 2.6 +/- 2.6 (P = 0.009), respectively. The number needed to treat to avoid one patient undergoing significant pain (pain score >= 4/10) was 2.75. Body mass index >25 kg/m2 was significantly associated with higher pain intensity (P = 0.03). No serious adverse events were attributable to 50% N2 O-O2 inhalation. CONCLUSIONS: Inhalation of a fixed 50% N2 O-O2 mixture is efficient to reduce LP-induced pain and anxiety. PMID- 27666150 TI - Assesment of severity and changes in C-reactive protein concentration and various biomarkers in dogs with pancreatitis. AB - Canine pancreatitis is a relatively common disorder, and its mortality rate remains high. However, prognostic factors for pancreatitis based on evidence are limited. Moreover, the relationship between changes in C-reactive protein (CRP) concentration-an important prognostic factor for human patients with acute pancreatitis-and the prognosis of dogs with pancreatitis has not been widely studied. Therefore, we examined prognostic factors for canine pancreatitis during the first medical examination and evaluated the usefulness of serial CRP measurements during hospitalization. Sixty-five dogs met the inclusion criteria, including 22 that were hospitalized and treated. In Study 1, a multivariate analysis revealed that three factors- decreased platelet count and a marked (greater than 1,000 ug/l) elevation of specific canine pancreatic lipase (Spec cPL) concentration at the first medical examination, as well as elevated blood urea nitrogen (BUN) and/or creatinine (CRE) level-were significantly different between the survivors and nonsurvivors. Moreover, CRP concentrations on the third and fourth days were significantly different between the two groups in Study 2. An evaluation of the decreased platelet count, remarkable elevation of Spec cPL concentration at the first medical examination, elevation of BUN and/or CRE as well as serial CRP concentration measurements may be useful for predicting the prognosis of canine pancreatitis. PMID- 27666151 TI - United we stand: Adhesion and molecular mechanisms driving cell fusion across species. AB - Cell-cell fusion is a physiological process playing an essential role for fertilization, shaping organs, tissue repair and immune defense in multicellular organisms. Recent research in the field aims to understand why two or more cells fuse each other and to decipher the general mechanisms regulating this process. Few basic and general steps can be identified, i.e. migration, adhesion and fusion, which are common to different types of cells. As pre-fused and fused cells undergo dramatic changes in their ultrastructure and behavior, the coordinated action of multiple factors is required, including adhesion molecules, cell surface receptors, intracellular kinases, transcription factors, and miRNAs. Although a number of reviews on cell-cell fusion have been published over the years, comprehensive reviews that broadly summarize this process including extracellular and intracellular cues are lacking. For example, a link between cell fusion and adhesive molecules and/or miRNAs has rarely been highlighted in the recent literature. In this review, we will summarize some molecular mechanisms controlling the process of somatic cell-cell fusion during embryonic development. We will specially focus on adhesive molecules, ECM components and miRNAs, providing a summary of important findings on their role in mediating this process in few model systems, in vertebrate and invertebrate organisms. PMID- 27666152 TI - Coping and posttraumatic stress symptoms in children with food allergies. PMID- 27666153 TI - Can the paleolithic diet meet the nutritional needs of older people? PMID- 27666154 TI - National Registry of Designated Intractable Diseases in Japan: Present Status and Future Prospects. AB - Japan promotes research related to intractable diseases and financially supports patients with these diseases. Intractable diseases are designated as those that fulfill the following criteria: (1) rarity (affecting less than 0.1% of the population in Japan), (2) unknown etiology, (3) lack of effective treatment, (4) necessity of long-term treatment, and (5) existence of objective diagnostic criteria and not necessarily equal to rare diseases in other countries. The construction of a national database is required to promote research to clarify the pathogenesis of these diseases and to develop pharmaceutical products and medical devices. The Ministry of Health, Labor, and Welfare launched an online registration system in 2001, but many problems associated with gathering and utilizing information on patients with intractable diseases remain. In this paper, we describe the present status of the national registry of designated intractable diseases in Japan and discuss future prospects. PMID- 27666155 TI - "Milky" bowel and malrotation. PMID- 27666156 TI - Comparison Between Steroid and 2 Different Sites of Botulinum Toxin Injection in the Treatment of Lateral Epicondylalgia: A Randomized, Double-Blind, Active Drug Controlled Pilot Study. AB - OBJECTIVE: To compare the effects of 2 different injection sites of low doses of botulinum toxin type A with steroid in treating lateral epicondylalgia. DESIGN: Double-blind, randomized, active drug-controlled trial. SETTING: Tertiary medical center. PARTICIPANTS: Patients with lateral epicondylalgia for >6 months were recruited from a hospital-based outpatient population (N=26). A total of 66 patients were approached, and 40 were excluded. No participant withdrew because of adverse effects. INTERVENTIONS: Patients were randomly assigned into 3 groups: (1) botulinum toxin epic group (n=8), who received 20U of botulinum toxin injection into the lateral epicondyle; (2) botulinum toxin tend group (n=7), who received 20U of botulinum toxin injected into tender points of muscles; and (3) steroid group (n=11), who received 40mg of triamcinolone acetonide injected into the lateral epicondyle. MAIN OUTCOME MEASURES: A visual analog scale, a dynamometer, and the Patient-Rated Tennis Elbow Evaluation were used to evaluate the perception of pain, maximal grip strength, and functional status, respectively. Outcome measures were assessed before intervention and at 4, 8, 12, and 16 weeks after treatment. The primary outcome measure was a visual analog scale. RESULTS: At 4 weeks after injection, the steroid group was superior to the botulinum toxin tend group in improvement on the visual analog scale (P=.006), grip strength (P=.03), and Patient-Rated Tennis Elbow Evaluation (P=.02). However, these differences were not observed at the 8-, 12-, and 16-week follow up assessments. There was no significant difference between the steroid and botulinum toxin epic groups. CONCLUSIONS: Injections with botulinum toxin and steroid effectively reduced pain and improved upper limb function in patients with lateral epicondylalgia for at least 16 weeks. The onset of effect was earlier in the steroid and botulinum toxin epic groups than in the botulinum toxin tend group. PMID- 27666157 TI - Step-Count Accuracy of 3 Motion Sensors for Older and Frail Medical Inpatients. AB - OBJECTIVE: To measure the step-count accuracy of an ankle-worn accelerometer, a thigh-worn accelerometer, and a pedometer in older and frail inpatients. DESIGN: Cross-sectional design study. SETTING: Research room within a hospital. PARTICIPANTS: Convenience sample of inpatients (N=32; age, >=65 years) who were able to walk 20m independently with or without a walking aid. INTERVENTIONS: Patients completed a 40-minute program of predetermined tasks while wearing the 3 motion sensors simultaneously. Video recording of the procedure provided the criterion measurement of step count. MAIN OUTCOME MEASURES: Mean percentage errors were calculated for all tasks, for slow versus fast walkers, for independent walkers versus walking-aid users, and over shorter versus longer distances. The intraclass correlation was calculated, and accuracy was graphically displayed by Bland-Altman plots. RESULTS: Thirty-two patients (mean age, 78.1+/-7.8y) completed the study. Fifteen (47%) were women, and 17 (51%) used walking aids. Their median speed was .46m/s (interquartile range [IQR], .36 .66m/s). The ankle-worn accelerometer overestimated steps (median error, 1% [IQR, -3% to 13%]). The other motion sensors underestimated steps (median error, 40% [IQR, -51% to -35%] and 38% [IQR -93% to -27%], respectively). The ankle-worn accelerometer proved to be more accurate over longer distances (median error, 3% [IQR, 0%-9%]) than over shorter distances (median error, 10% [IQR, -23% to 9%]). CONCLUSIONS: The ankle-worn accelerometer gave the most accurate step-count measurement and was most accurate over longer distances. Neither of the other motion sensors had acceptable margins of error. PMID- 27666158 TI - Nested Cohort Study to Identify Characteristics That Predict Near-Term Disablement From Lung Cancer Brain Metastases. AB - OBJECTIVE: To test whether the presence of patient- and imaging-level characteristics (1) are associated with clinically meaningful changes in mobility among patients with late-stage cancer with metastatic brain involvement, and (2) can predict their risk of near-term functional decline. DESIGN: Prospective nested cohort study. SETTING: Quaternary academic medical center. PARTICIPANTS: The study population consisted of a nested cohort of the patients with imaging confirmed brain metastases (n=66) among a larger cohort of patients with late stage lung cancer (N=311). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional evaluations with the Activity Measure for Post-Acute Care Computer Adaptive Test (AM-PAC-CAT) and symptom intensity ratings were collected at monthly intervals for up to 2 years. RESULTS: In exploratory univariate models, whole brain radiation therapy (WBRT) and imaging findings of cerebellar or brainstem involvement were associated with large AM-PAC-CAT score declines reflecting worsening mobility (-4.55, SE 1.12; -2.87, SE, 1.0; and -3.14, SE 1.47, respectively). Also in univariate models, participants with new neurologic signs or symptoms at imaging (-2.48; SE .99), new brain metastases (-2.14, SE .99), or new and expanding metastases (-2.64, SE 1.14) declined significantly. Multivariate exploratory mixed logistic models, including WBRT, cerebellar/brainstem location, presence of new and expanding metastases, and worst pain intensity, had excellent predictive capabilities for AM-PAC-CAT score declines of 7.5 and 10 points (C statistics >=0.8). CONCLUSIONS: Among patients with lung cancer and brain metastases, cerebellar/brainstem location, new and expanding metastases, and treatment with WBRT may predict severe, near-term mobility losses and indicate a need to consider rehabilitation services. PMID- 27666159 TI - Correlates of Perceived Ankle Instability in Healthy Individuals Aged 8 to 101 Years. AB - OBJECTIVES: To provide reference data for the Cumberland Ankle Instability Tool (CAIT) and to investigate the prevalence and correlates of perceived ankle instability in a large healthy population. DESIGN: Cross-sectional observational study. SETTING: University laboratory. PARTICIPANTS: Self-reported healthy individuals (N=900; age range, 8-101y, stratified by age and sex) from the 1000 Norms Project. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed the CAIT (age range, 18-101y) or CAIT-Youth (age range, 8-17y). Sociodemographic factors, anthropometric measures, hypermobility, foot alignment, toes strength, lower limb alignment, and ankle strength and range of motion were analyzed. RESULTS: Of the 900 individuals aged 8 to 101 years, 203 (23%) had bilateral and 73 (8%) had unilateral perceived ankle instability. The odds of bilateral ankle instability were 2.6 (95% confidence interval [CI], 1.7-3.8; P<.001) times higher for female individuals, decreased by 2% (95% CI, 1%-3%; P=.001) for each year of increasing age, increased by 3% (95% CI, 0%-6%; P=.041) for each degree of ankle dorsiflexion tightness, and increased by 4% (95% CI, 2% 6%, P<.001) for each centimeter of increased waist circumference. CONCLUSIONS: Perceived ankle instability was common, with almost a quarter of the sample reporting bilateral instability. Female sex, younger age, increased abdominal adiposity, and decreased ankle dorsiflexion range of motion were independently associated with perceived ankle instability. PMID- 27666161 TI - MRI contrast agents: Classification and application (Review). AB - Magnetic resonance imaging (MRI) contrast agents are categorised according to the following specific features: chemical composition including the presence or absence of metal atoms, route of administration, magnetic properties, effect on the magnetic resonance image, biodistribution and imaging applications. The majority of these agents are either paramagnetic ion complexes or superparamagnetic magnetite particles and contain lanthanide elements such as gadolinium (Gd3+) or transition metal manganese (Mn2+). These elements shorten the T1 or T2 relaxation time, thereby causing increased signal intensity on T1 weighted images or reduced signal intensity on T2-weighted images. Most paramagnetic contrast agents are positive agents. These agents shorten the T1, so the enhanced parts appear bright on T1-weighted images. Dysprosium, superparamagnetic agents and ferromagnetic agents are negative contrast agents. The enhanced parts appear darker on T2-weighted images. MRI contrast agents incorporating chelating agents reduces storage in the human body, enhances excretion and reduces toxicity. MRI contrast agents may be administered orally or intravenously. According to biodistribution and applications, MRI contrast agents may be categorised into three types: extracellular fluid, blood pool and target/organ-specific agents. A number of contrast agents have been developed to selectively distinguish liver pathologies. Some agents are also capable of targeting other organs, inflammation as well as specific tumors. PMID- 27666160 TI - Effectiveness of Aquatic Exercise in Improving Lower Limb Strength in Musculoskeletal Conditions: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: To investigate the effectiveness of aquatic exercise in improving lower limb strength in people with musculoskeletal conditions. DATA SOURCES: A systematic search used 5 databases, including MEDLINE, CINAHL, Embase, SPORTDiscus, and The Cochrane Library. STUDY SELECTION: Randomized controlled trials evaluating aquatic exercise with a resistance training component for adults with musculoskeletal conditions compared with no intervention or land based exercise were identified. Fifteen studies from the initial yield of 1214 met these criteria. DATA EXTRACTION: Data related to participant demographics, study design, and methods, interventions, and outcomes, including numerical means and SDs, were extracted independently by 2 reviewers. DATA SYNTHESIS: Nine of the 15 studies were of high quality, scoring at least 6 on the Physiotherapy Evidence Database Scale. Limited consideration of the prescription of resistance in the aquatic exercise and application of resistance training principles existed. Low- or very low-quality evidence indicates there was no difference in average effect between aquatic exercise and no exercise in improving hip abductor strength (standardized mean difference [SMD], .28; 95% confidence interval [CI], -.04 to .59), knee extensor strength (SMD, .18; 95% CI, -.03 to .40), knee flexor strength (SMD, .13; 95% CI, -.20 to .45), or lower limb endurance (SMD, .35; 95% CI, -.06 to .77). Low-quality evidence indicates no difference in average effect between aquatic and land exercise for knee extensor (SMD, -.24; 95% CI, -.49 to .02) or flexor strength (SMD, -.15; 95% CI, -.53 to .22). CONCLUSIONS: It is likely that the inadequate application of resistance in water is a significant contributor to the limited effectiveness of aquatic exercise interventions in improving hip and knee muscle strength in people with musculoskeletal conditions. Future research is needed to quantify resistance with aquatic exercises and to determine if using opportunities for greater resistance in aquatic rehabilitation and appropriate resistance training principles can be more effective in improving muscle strength. PMID- 27666163 TI - Personality modulates proportions of CD4+ regulatory and effector T cells in response to socially induced stress in a rodent of wild origin. AB - The way how individuals respond to chronic challenges can vary tremendously, and such differences are closely linked to personality. The few available studies on individual differences in stress-related immunosuppression in non-human mammals have been mainly carried out with laboratory strains. We conducted a study in male mound-building mice (Mus spicilegus) of wild origin. We distinguished between high (HAN) and low anxious/neophobic (LAN) personality types, quantified by subjects' consistent and associated behavioral responses in repeated elevated plus maze and novel object tests. After reaching maturity, parts of the subjects were regularly confronted to different resident pairs over a period of 5days to provoke a condition of chronic social stress, while others were used as untreated controls. We measured fecal corticosteroid metabolite (FCM) concentrations and different cellular immune parameters from blood and spleen. Socially confronted HAN showed higher increases in FCM concentrations than LAN, indicating a more pronounced physiological stress response in the former personality type. HAN of the experimental group also showed lower percentages of effector T cells (Teff) and higher regulatory T cells (Treg) in the spleen; the latter are known for their immunosuppressive activity. Considering the ratio of Teff/Treg, animals with higher increases in FCM concentrations during the late period of the experiment showed a stronger shift towards Treg cells, supporting immunosuppressive effects of chronically elevated corticosteroid levels. Summarizing, our results strongly suggest that immunomodulatory effects of socially induced stress were altered by individual differences in anxiety/neophobia, emphasizing the significance of personality in shaping physiological responses to challenge. PMID- 27666162 TI - Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle. AB - OBJECTIVE: 17beta-Estradiol (17betaE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17betaE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17betaE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL VMN glucose-sensing neurons (GSNs). METHODS: These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17betaE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. RESULTS: The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17betaE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17betaE application. CONCLUSION: These data suggest that physiological fluctuations in circulating 17betaE levels across the estrous cycle lead to changes in hypothalamic glucose sensing and the response to IIH. PMID- 27666164 TI - Molecular Cytogenetics as a Diagnostic Aid for Primary Liposarcoma of the Spermatic Cord. PMID- 27666165 TI - Melatonin induces cell apoptosis in Mia PaCa-2 cells via the suppression of nuclear factor-kappaB and activation of ERK and JNK: A novel therapeutic implication for pancreatic cancer. AB - Melatonin is synthesized by the pineal gland and is released into the blood. In the last several years, some studies have shown that melatonin has anticancer properties; however, the mechanisms behind the antitumour traits are unclear, especially in pancreatic cancer. Therefore, in the present study, we investigated the antitumour effects of melatonin on the human pancreatic carcinoma cell line MIA PaCa-2 and explored its biological mechanisms. MIA PaCa-2 cells were treated with melatonin, and we used a CCK-8 assay to evaluate the cell viability. We also used flow cytometry to observe cell apoptosis and western blot analysis to assess the protein expression. Our study found that melatonin inhibited cell viability, suppressed colony formation and reduced cell migration and invasion and induced cell apoptosis in MIA PaCa-2 cells. Our results showed that melatonin treatment inhibited NF-kappaB p65 activation. Moreover, melatonin treatment activated the mitogen-activated protein kinase pathways (c-jun N-terminal kinase and extracellular-regulated kinase 1/2), which increased Bax protein expression and caspase-3 cleavage and decreased Bcl-2 protein expression. These new developments demonstrate that melatonin plays a potential role in anticancer treatment and may act as an effective therapeutic agent in the future. PMID- 27666166 TI - Mechanisms of protein nanoscale clustering. AB - Due to recent technical developments in microscopy, huge advances have been made in our understanding of the architecture of the cell membrane. It is now well appreciated that nanoscale clustering is a common feature of membrane proteins. Many of these clusters have been implicated in signal initiation and integration platforms. However, the mechanisms that mediate the dynamic nanoscale arrangement of membrane proteins are not fully understood and could involve lipid domains, electrostatic interactions between proteins and lipid, protein scaffolding as well as purely mechanical processes. In this review we summarise these mechanisms giving rise to dynamic nanoscale protein reorganisation in the plasma membrane with reference to recent examples of immune receptor clustering to illustrate general principles. PMID- 27666169 TI - Pregnant women: What do they need to know during pregnancy? A descriptive study. AB - BACKGROUND: Antenatal education programs provide women with essential knowledge and skills in various aspects of maternal and fetal health. Antenatal education is based on improving women's health, reducing the risks of complications and enhancing couples' positive experience during childbirth. There is a lack of formal antenatal educational programs based on women's needs in Jordan. AIM: This study sought to identify and prioritize the learning needs for women during pregnancy. METHODS: A descriptive cross-sectional design was employed. The study sample was recruited from three maternal and child health centers. Data were collected from a convenient sample of 150 pregnant women during their antenatal visits. One hundred and twenty three participants (response rate=82%) completed the self-reported antenatal learning needs questionnaire. FINDINGS: Women identified their most important learning needs were related to managing major complications of pregnancy (mean=3.49, SD=0.78), investigations and physician follow-up visit during pregnancy (mean=3.42, SD=0.71), appropriate diet (mean=3.36, SD=0.84) and information about medication and supplements (mean=3.22, SD=0.97). Spearman correlation showed negative association between participants' age and physical (r=-0.536, p=0.015) and emotional concerns (r=-0.490, p=0.001). Women who had a diploma or higher degree reported greater concern regarding physical (median=4.00, IQR=3.00-4.00, p=0.047) and emotional changes (median=3.33, IQR=3.00-4.00, p=0.004). Finally, migrant participants showed greater significant concern regarding emotional changes and coping with minor complications. CONCLUSION: A large proportion of pregnant women in this study reported a high degree of importance of specific learning topics that were closely relevant to their current period of pregnancy. The lack of focusing on issues related to maternal emotional status and possible complications suggests a need for a national strategy to provide antenatal education based on women's perceptions of their needs. PMID- 27666167 TI - Microtubule-organizing centers: from the centrosome to non-centrosomal sites. AB - The process of cellular differentiation requires the distinct spatial organization of the microtubule cytoskeleton, the arrangement of which is specific to cell type. Microtubule patterning does not occur randomly, but is imparted by distinct subcellular sites called microtubule-organizing centers (MTOCs). Since the discovery of MTOCs fifty years ago, their study has largely focused on the centrosome. All animal cells use centrosomes as MTOCs during mitosis. However in many differentiated cells, MTOC function is reassigned to non centrosomal sites to generate non-radial microtubule organization better suited for new cell functions, such as mechanical support or intracellular transport. Here, we review the current understanding of non-centrosomal MTOCs (ncMTOCs) and the mechanisms by which they form in differentiating animal cells. PMID- 27666168 TI - Association between chest compression rates and clinical outcomes following in hospital cardiac arrest at an academic tertiary hospital. AB - AIMS: Recent guidelines for management of cardiac arrest recommend chest compression rates of 100-120 compressions/min. However, animal studies have found cardiac output to increase with rates up to 150 compressions/min. The objective of this study was to test the association between chest compression rates during cardiopulmonary resuscitation for in-hospital cardiac arrest (IHCA) and outcome. METHODS: We conducted a prospective observational study at a single academic medical center. INCLUSION CRITERIA: age>=18, IHCA, cardiopulmonary resuscitation performed. We analyzed chest compression rates measured by defibrillation electrodes, which recorded changes in thoracic impedance. The primary outcome was return of spontaneous circulation (ROSC). We used multivariable logistic regression to determine odds ratios for ROSC by chest compression rate categories (100-120, 121-140, >140 compressions/min), adjusted for chest compression fraction (proportion of time chest compressions provided) and other known predictors of outcome. We set 100-120 compressions/min as the reference category for the multivariable model. RESULTS: We enrolled 222 consecutive patients and found a mean chest compression rate of 139+/-15. Overall 53% achieved ROSC; among 100-120, 121-140, and >140 compressions/min, ROSC was 29%, 64%, and 49% respectively. A chest compression rate of 121-140 compressions/min had the greatest likelihood of ROSC, odds ratio 4.48 (95% CI 1.42-14.14). CONCLUSIONS: In this sample of adult IHCA patients, a chest compression rate of 121-140 compressions/min had the highest odds ratio of ROSC. Rates above the currently recommended 100-120 compressions/min may improve the chances of ROSC among IHCA patients. PMID- 27666170 TI - Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study). AB - Previous studies have shown several metabolic biomarkers to be associated with prevalent and incident atrial fibrillation (AF), but the results have not been replicated. We investigated metabolite profiles of 2,458 European ancestry participants from the Framingham Heart Study without AF at the index examination and followed them for 10 years for new-onset AF. Amino acids, organic acids, lipids, and other plasma metabolites were profiled by liquid chromatography tandem mass spectrometry using fasting plasma samples. We conducted Cox proportional hazard analyses for association between metabolites and new-onset AF. We performed hypothesis-generating analysis to identify novel metabolites and hypothesis-testing analysis to confirm the previously reported associations between metabolites and AF. Mean age was 55.1 +/- 9.9 years, and 53% were women. Incident AF developed in 156 participants (6.3%) in 10 years of follow-up. A total of 217 metabolites were examined, consisting of 54 positively charged metabolites, 59 negatively charged metabolites, and 104 lipids. None of the 217 metabolites met our a priori specified Bonferroni corrected level of significance in the multivariate analyses. We were unable to replicate previous results demonstrating associations between metabolites that we had measured and AF. In conclusion, in our metabolomics approach, none of the metabolites we tested were significantly associated with the risk of future AF. PMID- 27666171 TI - Frequency of and Prognostic Significance of Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valve Implantation. AB - The prognostic implications of preexisting atrial fibrillation (AF) and new-onset AF (NOAF) in transcatheter aortic valve implantation (TAVI) remain uncertain. This study assesses the epidemiology of AF in patients treated with TAVI and evaluates their outcomes according to the presence of preexisting AF or NOAF. A retrospective analysis of 708 patients undergoing TAVI from 2 heart hospitals was performed. Patients were divided into 3 study groups: sinus rhythm (n = 423), preexisting AF (n = 219), and NOAF (n = 66). Primary outcomes of interest were all-cause death and stroke both at 30-day and at 1-year follow-up. Preexisting AF was present in 30.9% of our study population, whereas NOAF was observed in 9.3% of patients after TAVI. AF and NOAF patients showed a higher rate of 1-year all cause mortality compared with patients in sinus rhythm (14.6% vs 6.5% for preexisting AF and 16.3% vs 6.5% for NOAF, p = 0.007). No differences in 30-day mortality were observed between groups. In patients with AF (either preexisting and new-onset), those discharged with single antiplatelet therapy displayed higher mortality rates at 1 year (42.9% vs 11.7%, p = 0.006). Preexisting AF remained an independent predictor of mortality at 1-year follow-up (hazard ratio [HR] 2.34, 95% CI 1.22 to 4.48, p = 0.010). Independent predictors of NOAF were transapical and transaortic approach as well as balloon postdilatation (HR 3.48, 95% CI 1.66 to 7.29, p = 0.001; HR 5.08, 95% CI 2.08 to 12.39, p <0.001; HR 2.76, 95% CI 1.25 to 6.08, p = 0.012, respectively). In conclusion, preexisting AF is common in patients undergoing TAVI and is associated with a twofold increased risk of 1-year mortality. This negative effect is most pronounced in patients discharged with single antiplatelet therapy compared with other antithrombotic regimens. PMID- 27666172 TI - Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat With Incident Atrial Fibrillation (from the Framingham Heart Study). AB - Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third-Generation Cohorts who participated in the multidetector computed tomography substudy examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and gender-adjusted incident AF rate per 1,000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and gender adjusted model, greater pericardial fat (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03 to 1.34) and intrathoracic fat (HR 1.24, 95% CI 1.06 to 1.45) were associated with an increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99 to 1.30) for pericardial fat, 1.19 (1.01 to 1.40) for intrathoracic fat, and 1.09 (0.93 to 1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of body mass index, none of the associations remained significant (all p >0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. PMID- 27666173 TI - Symptom-Onset-To-Balloon Time, ST-Segment Resolution and In-Hospital Mortality in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention in China: From China Acute Myocardial Infarction Registry. AB - Animal and imaging study evidence favors early reperfusion for acute myocardial infarction. However, in clinical trials, the effect of symptom-onset-to-balloon (S2B) time on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) has been inconsistent. Moreover, there are few data regarding the ischemic time in China. A total of 3,877 consecutive patients with STEMI with available S2B time undergoing pPCI from January 2013 to September 2014 at 108 hospitals that participated in the China Acute Myocardial Infarction registry were included and stratified into 3 S2B groups: <6 hours, 6 to 12 hours, >12 hours S2B time was tested in multivariate logistic regression analyses as an independent risk factor of mortality (primary outcome), major adverse cardiovascular and cerebrovascular events (MACCE), and impaired myocardial perfusion (secondary outcomes). The median S2B time was 5.5 (3.75 to 8.50) hours. Longer S2B time was associated with higher in-hospital mortality (<6 hours: 2.7%; 6 to 12 hours: 3.4%; >12 hours: 4.9%; p = 0.047) and ST-segment resolution <50% (<6 hours: 16.7%; 6 to 12 hours: 19.2%; >12 hours: 24.3%; p = 0.002) but not MACCE. In multivariate-adjusted analysis, S2B >12 hours remained associated with ST-segment resolution <50% (odds ratio 1.53, 95% confidence interval 1.16 to 2.01, p = 0.002) but not with in hospital mortality (odds ratio 1.673, 95% confidence interval 0.95 to 2.94, p = 0.073). In conclusion, median S2B time in patients with STEMI undergoing pPCI was longer than that in registry studies from other countries. Longer S2B time was associated with impaired myocardial perfusion but not with in-hospital mortality or MACCE. PMID- 27666174 TI - Comparison in Men Versus Women of Co-morbidities, Complications, and Outcomes After Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis. AB - Transcatheter aortic valve implantation (TAVI) decreases mortality in high-risk patients with severe aortic stenosis, but it remains unclear if female gender is associated with more favorable outcomes after TAVI. All patients who underwent TAVI at a single institution were retrospectively analyzed and stratified by gender. Procedural, in-hospital, 30-day, and 1-year outcomes were defined according to the second Valve Academic Research Consortium. The primary end point was all-cause mortality at 1 year. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were conducted. Overall, 755 patients underwent TAVI and were included in the study; 50.7% were women. Average age was 83.0 +/- 7.7 years, with a mean Society of Thoracic Surgeons score of 8.9 +/- 4.6. Women were older than men and more likely to be black. Most co morbidities were less common among women, and they were more likely than men to suffer both in-hospital (8.4% vs 4.3%, p = 0.021) and 30-day (9.4% vs 5.4%, p = 0.035) all-cause mortality. Life-threatening bleeding, transfusion, and iliofemoral dissection or perforation were more common among women. There was no difference in mortality between women and men at 1 year (20.6% vs 21.5%, log-rank p = 0.87). After multivariable adjustment, however, female gender was independently associated with lower mortality at 1 year after TAVI. In conclusion, despite higher rates of major bleeding, vascular complications, and 30-day mortality, female gender was independently associated with improved survival at 1 year after TAVI. PMID- 27666175 TI - Diabetes-Invoked High-Density Lipoprotein and Its Association With Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus. AB - Although high-density lipoprotein (HDL) can exhibit anti-inflammatory properties, these potent activities can become deficient and even transform into proinflammatory effects under various pathophysiological states. We investigated the effect of diabetic HDL on the inflammatory response in human monocytes and its relation to the existence of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM). HDL was isolated from DM patients with (n = 61) or without (n = 31) CAD (diameter stenosis >=50%) and healthy controls (n = 40). Human peripheral blood mononuclear cells were incubated with HDL and the proinflammatory ability of HDL was determined by tumor necrosis factor-alpha (TNF alpha) secretion in peripheral blood mononuclear cells. Secretion of TNF-alpha in human monocytes in response to diabetic HDL was significantly increased compared with that of the control HDL. Of note, HDL from DM patients with CAD stimulated the release of TNF-alpha in monocytes to a greater extent than that of HDL from those without CAD. Multiple linear regression analysis showed that the proinflammatory ability of HDL was independently associated with diabetes duration, hemoglobin A1c, serum levels of high-sensitivity C-reactive protein (hs CRP) and reduced glomerular filtration rate (GFR). Furthermore, the proinflammatory ability of HDL was a significant predictor for the presence of CAD in patients with DM. PMID- 27666176 TI - Prevalence and Clinical Significance of an E-Reversal Wave in the Left Ventricular Outflow Tract. AB - Diastolic waves are commonly seen in the left ventricular outflow tract on echocardiography. This work focuses on the E-reversal wave (Er) that occurs early in diastole, shortly after the mitral E wave. Factors associated with Er presence and velocity were investigated in a broad patient sample: 100 subjects with normal ejection fraction (EF >55%) and 100 subjects with reduced EF (<45%). Er presence was noted in 58% of the total cohort and correlated inversely with age. It was more common with normal EF (70% vs 45%, p = 0.0005) and was associated with higher mitral E velocity (78.3 +/- 23.3 vs 68.4 +/- 19.0 cm/s; p = 0.002) and septal e' velocity (6.7 +/- 2.5 vs 5.3 +/- 2.3 cm/s; p <0.0001). Er velocity was higher in the normal EF group (50 +/- 18 vs 34 +/- 13 cm/s, p <0.0001) and showed moderate correlation with septal e' velocity (r = 0.43; p <0.0001); 56 subjects experienced major adverse cardiovascular events (MACE) over 1.7 +/- 0.3 years of follow-up. Those with an Er had less MACE (particularly heart failure), even after adjustment for multiple clinical and echocardiographic variables (OR 0.28, 95% CI 0.11 to 0.65; p = 0.003). When stratified by EF, the association between Er presence and MACE was significant only in the low EF group. Thus, Er occurs more commonly in younger subjects and those with preserved EF. It is associated with less MACE although this effect appears to be limited to patients with reduced EF. PMID- 27666177 TI - Meta-Analysis of Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes and All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus. AB - The benefit or risk of sodium glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus has not been established. We aimed to assess the comparative CV safety and mortality risk associated with the use of SGLT2 inhibitors. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were systematically searched up to January 27, 2016, to identify randomized controlled trials (RCTs) with the use of SGLT2 inhibitors of at least 24 weeks of duration. The primary outcomes included all-cause mortality and major adverse cardiovascular events. A random-effects network meta-analysis was performed to calculate the odds ratio (OR) with 95% CI. We identified 37 eligible trials involving 29,859 patients that compared 3 SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to placebo and other active antidiabetic treatments. Of all direct and indirect comparisons, only empagliflozin compared with placebo was significantly associated with lower risk of all-cause mortality (OR 0.67, 95% CI 0.56 to 0.81) and major adverse cardiovascular events (OR 0.81, 95% CI 0.70 to 0.93). However, the significant effect of empagliflozin was largely driven by one large randomized trial (EMPA-REG OUTCOME trial). Neither dapagliflozin nor canagliflozin was significantly associated with any harm. In conclusion, current RCT evidence suggests that 3 common SGLT2 inhibitors are not associated with increased risk of all-cause mortality and CV outcomes when used to treat patients with type 2 diabetes mellitus. Although empagliflozin may have a protective effect, further confirmative data from rigorous RCTs are needed. PMID- 27666178 TI - Usefulness of Measuring the Serum Elastin Fragment Level in the Diagnosis of an Acute Aortic Dissection. AB - Previous reports have shown that serum elastin fragments (SEFs) may be a useful biomarker for the diagnosis of an acute aortic dissection (AAD). However, because the reference interval of SEFs has not been established, it has not been determined whether SEFs are really useful for the diagnosis of AAD. The purpose of this study was to determine the usefulness of measuring SEFs for the diagnosis of AAD. A total of 42 consecutive patients aged 68 +/- 18 years who were diagnosed with an AAD were studied. Patient background and SEF levels were examined on admission. SEF levels were also measured in patients undergoing a medical examination (n = 531, age 54 +/- 17 years) to compare with those with an AAD. In the control group, SEF levels increased with age (R = 0.725, p <0.001). Then, we defined the upper limit of the reference interval of SEF levels as the 97.5th percentile of control SEF grouped by decade of life from the sixth to ninth decade. The overall risk of AAD exceeding the upper limit of the reference interval at each decade was 10% (4 of 42). For patients in their 60s and 70s, median SEF levels in the AAD group (89 [77 to 104], 93 [60 to 123] ng/ml, respectively) were not significantly higher than those in the control group (79 [68 to 92], 90 [79 to 106] ng/ml, respectively; p = 0.081 and 0.990, respectively). Our data suggest that measuring SEF levels may not be useful in the diagnosis of an AAD as the upper limit of the reference interval of the SEF level was unexpectedly higher. PMID- 27666179 TI - Comparing Coronary Atheroma Progression Rates and Coronary Events in the United States, Canada, Latin America, and Europe. AB - We explored for geographic variations in coronary atheroma progression rates in the United States compared to other world regions (Canada, Latin America, Western Europe, and Central-Eastern Europe) and sought to ascertain if this associated with regional differences in major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, coronary revascularization). Across 7 randomized trials with a global recruitment pattern, 5,451 participants with angiographic coronary disease underwent serial coronary intravascular ultrasonography during 18 or 24 months, with adjudicated MACE. Change in coronary percent atheroma volume (DeltaPAV) and MACE in the United States versus other world regions were assessed. Despite similar baseline angiographic and plaque characteristics across participants and regions, following propensity-weighted and multivariate analysis, US (n = 3,706) versus non-US (n = 1,745) participants demonstrated marginal but significantly greater annualized DeltaPAV (least-square means +/- SE: 0.27 +/- 0.14% vs 0.062 +/- 0.14%, p = 0.005). However, MACE rates were disproportionately higher in US compared to non-US participants (23.5% vs 10.9%, p <0.001), driven by a doubling in crude rates of coronary revascularization procedures (16.1% vs 7.8%, p <0.001). The US participants hospitalized with unstable angina demonstrated more significant disease progression than their non-US counterparts (DeltaPAV: 0.57 +/ 0.19% vs -0.30 +/- 0.36%, p = 0.033) and greater MACE (9.1% vs 4.8%, p <0.001). A US geographic disposition independently associated with MACE (hazard ratio 1.53, 95% confidence interval 1.22 to 1.92, p <0.001). In conclusion, in participants with stable coronary disease, coronary atheroma progression rates are modestly higher in US-based compared to non-US-based participants. Elective coronary revascularization rates however are disproportionately greater in US based participants. PMID- 27666180 TI - Anticoagulation After Heart Valve Replacement or Transcatheter Valve Implantation. AB - Valvular heart disease is prevalent and represents a significant contributor to cardiac morbidity and mortality. Several options for valve replacement exist, including surgical replacement and transcatheter valve implantation. Prosthetic valves lead to increased risk of thromboembolic disease; therefore, antithrombotic therapy after valve replacement is indicated. For patients with mechanical prostheses, indefinite vitamin K antagonist and antiplatelet therapy are the mainstays of treatment. There is no consensus regarding optimal antithrombotic therapy after bioprosthetic valve replacement, although vitamin K antagonist therapy of varying duration in addition to antiplatelet therapy is recommended by guidelines. Dual-antiplatelet therapy is commonly used after transcatheter valve implantation; however, alternative antithrombotic regimens are being studied. Further studies are needed to identify the optimal regimen, intensity, and duration of antithrombotic therapy after surgical bioprosthetic valve replacement and transcatheter valve implantation. PMID- 27666181 TI - Prominent Intrapulmonary Bronchopulmonary Anastomoses and Abnormal Lung Development in Infants and Children with Down Syndrome. AB - OBJECTIVES: To determine the frequency of histologic features of impaired lung vascular and alveolar development and to identify the presence of intrapulmonary bronchopulmonary anastomoses (IBA) in infants and children who died with Down syndrome. STUDY DESIGN: A retrospective review of autopsy reports and lung histology from 13 children with Down syndrome (ages: 0-8 years) was performed. Histologic features of abnormal lung development were identified and semiquantified, including the presence of IBA. Three-dimensional reconstructions of IBA were also performed. Comparisons were made with 4 age-matched patients without Down syndrome with congenital heart defects who underwent autopsies during this time period. RESULTS: Of the 13 subjects with Down syndrome, 69% died from cardiac events, 77% had a congenital heart defect, and 46% had a clinical diagnosis of pulmonary hypertension. Lung histology from all subjects with Down syndrome demonstrated alveolar simplification, and 92% had signs of persistence of a double capillary network in the distal lung. The lungs from the subjects with Down syndrome frequently had features of pulmonary arterial hypertensive remodeling (85%), and prominent bronchial vessels and IBA were observed in all subjects with Down syndrome. These features were more frequent in subjects with Down syndrome compared with control subjects. CONCLUSIONS: Children with Down syndrome who died of cardiopulmonary diseases often have histologic evidence of impaired lung alveolar and vascular development, including the presence of prominent IBA and pulmonary hypertension. We speculate that children with Down syndrome are at risk for reduced lung surface area and recruitment of IBA, which may worsen gas exchange in subjects with Down syndrome. PMID- 27666182 TI - [Morbidity of bodylift. Evaluation of 111 patients over 5 years]. AB - INTRODUCTION: The management of patients with weight loss sequelae, sometimes major, is increasingly well standardized. However, this surgery is not without risk. Complications of bodylift are more frequent than those of conventional abdominoplasties. The objective of this study was to evaluate the morbidity associated with this surgery through a retrospective, single-center study. MATERIALS AND METHODS: One hundred and eleven circular abdominaloplasties were conducted between June 2011 and September 2015 in the plastic surgery department of the university hospital of Toulouse. Minor and major complications were identified and analyzed. RESULTS: Frequency of postoperative complications was 44.1% in our series. Major complications have involved 15.3% of patients. Blood transfusions (9%) and hematoma requiring reoperation (7.2%) were the most frequent major complications. We found significantly more major complications in patients with important fat resection with a cut off at 3200 g (P=0.02). Men experienced significantly more major complications than women (P=0.005). The average delta-BMI (before and after weight loss) was significantly higher in the group of patients with the highest percentage of minor complications (P=0.045). Indeed, a high delta-BMI (greater than 19.5) was associated with an excess risk of minor complications in our population. CONCLUSION: Democratization and progress in the field of bodylift should not obscure the fact that it is, in reality, a procedure at risk. While we manage increasingly better cosmetic results and thromboembolic complications, it still persists many complications. PMID- 27666183 TI - Assessment of anterior subcutaneous hypersignal on proton-density-weighted MR imaging of the knee and relationship with anterior knee pain. AB - PURPOSE: The purpose of this study was to evaluate the prevalence of anterior subcutaneous hypersignal indicating edema on proton-density (PD)-weighted MRI of the knee and to determine whether reporting anterior edema is clinically relevant. MATERIALS AND METHODS: One hundred and ninety-one knee MRIs from 162 patients were reviewed for anterior subcutaneous edema. There were 92 men and 70 women with a mean age of 41.72years+/-13.92 (SD) (range, 15-80years) years and a mean body weight of 75.94kg+/-12.54 (SD) (range, 50-130kg). The MRI findings were compared with patient age, gender, body weight, history of repetitive microtrauma and clinical findings. Patellar and trochlear chondropathy, medial plica, joint effusion, synovitis, infrapatellar fat-pad signal intensity, suprapatellar fat pad signal intensity with mass effect, quadriceps and patellar tendon abnormalities were also reviewed. RESULTS: An anterior hypersignal on PD-weighted MRI was detected in 158/191 MR examinations (82.7%) and 104 (84.6%) of these cases had histories of anterior knee pain. No correlation between anterior pain and anterior edema was found (P=0.42). Age (P<0.0001), weight (P<0.0001), and repetitive microtrauma (P=0.001) were identified as significant variables associated with anterior edema. CONCLUSION: Anterior edema may be a physiological phenomenon or degenerative change related to patient age, weight, and knee movement or mechanics. It should not be reported as a pathological finding on MRI unless clinical findings support regional infection or inflammation. PMID- 27666184 TI - Flavivirus RNA transactions from viral entry to genome replication. AB - Upon release of the ~11 kb single-stranded positive polarity dengue virus genomic RNA (gRNA) into the cytoplasm of an infected cell, it serves as the template for translation of the viral polyprotein, which is cleaved into three structural and seven non-structural proteins. The structural organization of the viral replication complex and RNA is not known but it is increasingly becoming evident that the viral gRNA and replication intermediates adopt unique structural features and localize to discrete regions in the infected cell. Both structure and location play multiple roles ranging from evasion of innate immune response to recruitment of viral and host proteins for translation and replication of the message. This review visits the various transactions that the viral gRNA undergoes between entry and RNA synthesis with the view that some of these events may be targeted by antiviral compounds. This article forms part of a symposium on flavivirus drug discovery in Antiviral Research. PMID- 27666185 TI - The effects of resveratrol on aging vessels. AB - Aging is a major risk factor for the development of cardiovascular disease. Despite a significant reduction in the mortality and morbidity rates over the last decade, the socio-economic burden of cardiovascular disease is still substantial. Consequently, there is a considerable need for alternative strategies, such as nutraceutical supplementation, that delay the functional vascular decline present in the elderly. Compromised autophagy and oxidative stress (OS) are considered major causes of the age-related endothelial dysfunction. OS reduces the bioavailability of nitric oxide (NO), which has been associated with hypertension, arteriosclerosis, and a reduced vasodilatory response. High levels of free radicals and the low bioavailability of NO lead to a positive feedback loop of further OS, organelle damage, poor repair, and endothelial dysfunction. Here we draw attention to the relationship between OS and autophagy in the aged vasculature. We have reviewed the published literature and provided arguments that support that treatment with resveratrol stimulates autophagy and thereby has the potential to restore oxidative balance in the endothelium, which indicates that treatment with resveratrol might have therapeutic potential to restore endothelial function in the elderly. PMID- 27666186 TI - Quantifying effects of age on balance and gait with inertial sensors in community dwelling healthy adults. AB - Although balance and gait deteriorate as a person ages, it is unknown if all balance and gait measures change similarly across the adult age span. We developed the Instrumented Stand and Walk test (ISAW) to provide a quick quantification of key components of balance and walking: postural sway, anticipatory postural adjustments during step initiation, gait, and turning using body-worn, inertial sensors. Our aims were to characterize how different balance and gait measures change with age and to identify key age-related measures of mobility, in a wide age range of healthy, community-dwelling adults. A total of 135 healthy, community-dwelling subjects of age range 21-89years with no history of falls were enrolled. Subjects wore inertial sensors on the wrists, ankles, sternum and lumbar area; 37 reliable and valid measures of postural sway, step initiation, gait and turning were computed. Univariate and multivariate regression analyses were performed to examine how the measures changed with age. Several distinct correlation patterns between age and ISAW measures were observed: linear deterioration, deterioration after plateau, and subtle, or no, worsening. Spatial, but not temporal, measures of gait were age-related. The strongest age correlation was found for centroidal frequency of mediolateral postural sway (r=-0.50, p<=0.001). A hierarchical regression model revealed that age was the most important predictor of mediolateral centroidal frequency, with lower sway frequencies associated with older age, independent of gender, weight, and height. Our results showed that balance and gait represent independent control systems for mobility and not all balance and gait measures deteriorate the same way with age. Postural sway during stance was more strongly related to age than any gait, gait initiation or turning measure. PMID- 27666187 TI - The detection of Trypanosoma cruzi by nested-PCR in elderly patients: relationship to the clinical and epidemiological profile. AB - Chagas disease, which is caused by Trypanosoma cruzi, is transmitted primarily by triatomine bugs, although the incidence of new cases has decreased as a result of vector control. In Brazil, most of those affected have the chronic form of the disease and are generally elderly individuals who require appropriate clinical follow-up. In this work, we undertook a descriptive study in which 85 patients were interviewed and blood samples were collected for molecular analyses based on the amplification of parasite satellite DNA. The cardiac form of the disease was the most prevalent among the patients and hypertension was the most frequent comorbidity; polypharmacy was detected in 34% of the cases. Serological tests were positive in 95% of cases while 36% were positive in nested-polymerase chain reaction. These findings indicate an increased use of medications and a larger number of age-related diseases in elderly patients with Chagas disease, even in patients with low parasitemia. We conclude that elderly patients with Chagas disease require special attention and that further studies should be done with elderly individuals who carry this disease. PMID- 27666188 TI - Cloning, characterization and comparative analysis of four death receptorTNFRs from the oyster Crassostrea hongkongensis. AB - Apoptosis plays an important role in homeostasis of the immune systems. The tumor necrosis factor receptors (TNFRs) play critical roles in the extrinsic apoptosis pathways and in determining cell fate. In this study, four death receptors (DR) named ChEDAR, ChTNFR27, ChTNFR5, and ChTNFR16 were identified from the oyster Crassostrea hongkongensis. These ChDRs proteins had 382, 396, 414 and 384 amino acids, respectively, with the typical domains of death receptors, such as the signal peptide (SP), transmembrane helix region (TM) and death domains. Phylogenetic analysis showed that the ChDR proteins clustered into three distinct groups, indicating that these subfamilies had common ancestors. mRNA expression of the ChDRs were detected in all 8 of the selected oyster tissues and at different stages of development. Furthermore, expression of all the genes was increased in the hemocytes of oysters challenged with pathogens or air stress. Fluorescence microscopy revealed that the full-length proteins of the ChDRs were located in the plasma membrane of HEK293T cells. Over-expression of the ChDRs activated the NF-kappaB-Luc reporter in HEK293T cells in a dose-dependent manner. These results indicate that the ChDRs may play important roles in the extrinsic apoptotic pathways in oysters. PMID- 27666189 TI - A member of the immunoglobulin superfamily, orange-spotted grouper novel immune gene EcVig, is induced by immune stimulants and type I interferon. AB - A novel grouper immune gene, EcVig was identified in orange-spotted grouper (Epinephelus coioides). We recently determined that EcVig expression can be induced by infection with nervous necrosis virus (NNV, an RNA virus), whereas NNV replication may be suppressed when EcVig was overexpressed. Although EcVig appeared to be involved in grouper antiviral activity, its immune effects have not been well characterized. In the present study, two PAMPs (pathogen-associated molecular patterns; lipopolysaccharides [LPS] and synthetic double-stranded RNA polyriboinosinic-polyribocytidylic acid [poly(I:C)]), as well as fish DNA virus (red sea bream iridovirus, RSIV; grouper iridovirus, GIV), were used to study EcVig responses in orange-spotted grouper. In addition, groupers were given recombinant type I interferon to determine whether EcVig expression was induced. Poly(I:C) rapidly induced substantial expression of EcVig, whereas LPS stimulation did not appear to have any effect in grouper intestine. Expression levels of total EcVig and other IFN-stimulated genes (ISGs) were all significantly increased after RSIV and GIV infection. Furthermore, stimulation of recombinant type I IFN also increased EcVig expression. We conclude that EcVig may be a novel IFN-stimulated gene that demonstrates an antiviral immune response. PMID- 27666190 TI - Salmonella spv locus suppresses host innate immune responses to bacterial infection. AB - Salmonella enterica serovar typhimurium (S. typhimurium) is globally distributed and causes massive morbidity and mortality in humans and animals. S. typhimurium carries Salmonella plasmid virulence (spv) locus, which is highly conserved and closely related to bacterial pathogenicity, while its exact role in host immune responses during infection remains to be elucidated. To counteract the invaders, the host has evolved numerous strategies, among which the innate immunity and autophagy act as the first defense. Recently, zebrafish has been universally accepted as a valuable and powerful vertebrate model in analyzing bacteria-host interactions. To investigate whether spv locus enhances the virulence of Salmonella by exerting an effect on the host early defense, zebrafish larvae were employed in this study. LD50 of S. typhimurium to zebrafish larvae and bacterial dissemination were analyzed. Sudan black B and neutral red staining were performed to detect the responses of neutrophils and macrophages to Salmonella infection. Autophagy agonist Torin1 and inhibitor Chloroquine were used to interfere in autophagic flux, and the protein level of Lc3 and p62 were measured by western blotting. Results indicated that spv locus could decrease the LD50 of S. typhimurium to zebrafish larvae, accelerate the reproduction and dissemination of bacteria by inhibiting the function of neutrophils and macrophages. Moreover, spv locus restrained the formation of autophagosomes in the earlier stage of autophagy. These findings suggested the virulence of spv locus involving in suppressing host innate immune responses for the first time, which shed new light on the role of spv operon in Salmonella pathogenicity. PMID- 27666191 TI - Antibacterial activity and modes of action of phosvitin-derived peptide Pt5e against clinical multi-drug resistance bacteria. AB - Pt5e, a mutant peptide derived from the C-terminal 55 residues of zebrafish phosvitin, has been suggested to be a novel antibacterial peptide. However, if it is applicable to clinical MDR bacteria remains to be tested. In this study, high purity Pt5e was first expressed and purified by fusion with cationic elastin-like polypeptide. Pt5e was then shown to be capable of effectively killing all the five clinical MDR bacteria tested. Pt5e kill the MDR bacteria at several levels, including inserting into the bacterial membranes, causing the membrane depolarization and permeabilization, and inducing the intracellular apoptosis/necrosis. All these data suggest that Pt5e is a promising therapeutic potential as an antibiotics against clinical MDR bacteria. PMID- 27666192 TI - Effects of medicinal herbs "Plantago asiatica", "Houttuynia cordata" and "Mentha haplocalyx" on non-specific immune responses of cobia (Rachycentron canadum). AB - This study investigated the effects of orally administered Plantago asiatica, Houttuynia cordata, and Mentha haplocalyx on the growth and nonspecific immune responses of cobia (Rachycentron canadum). The nonspecific immune parameters assessed were weight gain, feed conversion ratio, superoxide anion (O2-) production, superoxide dismutase (SOD) activity, phagocytic rate, phagocytic index, lysozyme activity, serum albumin and globulin, and albumin:globulin (A/G) ratio. The growth experiment indicated that 6-week dietary treatments did not significantly affect on the growth of cobia. Nonspecific immune responses showed that O2- production, SOD and lysozyme activity, and phagocytosis were significantly increased after the oral administration of P. asiatica and H. cordata, and the serum albumin:globulin ratio (A/G) gradually decreased. In this study, treatment of the Mentha haplocalyx on the cobia didn't present with the inducing of the phagocytosis ability compared with the treatment of P. asiatica and H. cordata. We suggest that oral administration of the 10 g/kg or 20 g/kg of the P. asiatica and H. cordata is exactly inducing the phagocytosis, ROS production, lysozyme activity and SOD production in the cobia. PMID- 27666193 TI - The challenges of modulating the 'rest and digest' system: acetylcholine receptors as drug targets. AB - Acetylcholine, a major neurotransmitter of the parasympathetic and sympathetic nervous systems, was discovered in the early 1900s. Over the years, researchers have revealed much about its regulation, properties of its receptors and features of the downstream signaling that influence its terminal effects. The acetylcholine system, traditionally associated with neuromuscular communication, is now known to play a crucial part in modulation of the immune system and other 'rest and digest' effects. Recent research seeks to elucidate the system's role in brain functions including cognition, sleep, arousal, motivation, reward and pain. We highlight clinically approved and experimental drugs that modulate the acetylcholine receptors. The complexities in targeting the acetylcholine receptors are vast and finding future indications for drug development associated with specific acetylcholine receptors remains a challenge. PMID- 27666194 TI - Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhibitors. AB - The flavoenzyme DprE1 catalyses a crucial step in arabinan production for cell wall biosynthesis in Mycobacterium tuberculosis and is a highly vulnerable drug target. It was first discovered using benzothiazinones (BTZ): exquisitely potent bactericidal agents that are being developed as drugs to treat tuberculosis. Subsequently, many compounds with diverse scaffolds were found to act as either covalent or noncovalent DprE1 inhibitors. Covalent inhibitors, like the BTZ, are all nitroaromatic compounds that serve as suicide substrates after DprE1-mediated nitroreduction. Here, we describe how high-resolution structures of DprE1, alone and in complex with various ligands, explain enzyme activity and inhibition. PMID- 27666196 TI - A viable method to predict acoustic streaming in presence of cavitation. AB - The steady liquid flow observed under ultrasonic emitters generating acoustic cavitation can be successfully predicted by a standard turbulent flow calculation. The flow is driven by the classical averaged volumetric force density calculated from the acoustic field, but the inertial term in Navier Stokes equations must be kept, and a turbulent solution must be sought. The acoustic field must be computed with a realistic model, properly accounting for dissipation by the cavitation bubbles [Louisnard, Ultrason. Sonochem., 19, (2012) 56-65]. Comparison with 20kHz experiments, involving the combination of acoustic streaming and a perpendicular forced flow in a duct, shows reasonably good agreement. Moreover, the persistence of the cavitation effects on the wall facing the emitter, in spite of the deflection of the streaming jet, is correctly reproduced by the model. It is also shown that predictions based either on linear acoustics with the correct turbulent solution, or with Louisnard's model with Eckart-Nyborg's theory yields unrealistic results. PMID- 27666195 TI - Sporicidal performance induced by photocatalytic production of organic peroxide under visible light irradiation. AB - Bacteria that cause serious food poisoning are known to sporulate under conditions of nutrient and water shortage. The resulting spores have much greater resistance to common sterilization methods, such as heating at 100 degrees C and exposure to various chemical agents. Because such bacteria cannot be inactivated with typical alcohol disinfectants, peroxyacetic acid (PAA) often is used, but PAA is a harmful agent that can seriously damage human health. Furthermore, concentrated hydrogen peroxide, which is also dangerous, must be used to prepare PAA. Thus, the development of a facile and safe sporicidal disinfectant is strongly required. In this study, we have developed an innovative sporicidal disinfection method that employs the combination of an aqueous ethanol solution, visible light irradiation, and a photocatalyst. We successfully produced a sporicidal disinfectant one hundred times as effective as commercially available PAA, while also resolving the hazards and odor problems associated with PAA. The method presented here can potentially be used as a replacement for the general disinfectants employed in the food and health industries. PMID- 27666197 TI - Effect of pulse repetition frequency of high-intensity focused ultrasound on in vitro thrombolysis. AB - Vascular occlusion by the thrombi is the main reason for ischemic stroke and deep vein thrombosis. High-intensity focused ultrasound (HIFU) and histotripsy or microtripsy pulses can effectively dissolve the blood clot with no use of thrombolytic agent and ultrasound contrast agent (microbubbles). In this study, HIFU bursts at the same duty cycle (2%) but varied pulse repetition frequency (PRF) from 1Hz to 1000Hz were delivered to in vitro porcine blood clot for 30s. Thrombolysis efficiency initially increases slightly with the PRF, 86.4+/-10.3%, 89.9+/-11.9, and 92.9+/-12.8% at the PRF of 1Hz, 10Hz, and 100Hz, respectively, without significant difference (p>0.05), but then drops dramatically to 37.9+/ 6.9% at the PRF of 1000Hz (p<0.05). The particle size in the supernatant of dissolution is 547.1+/-129.5nm, which suggests the disruption of thrombi into the subcellular level. Thrombi motion during HIFU exposure shows violent motion and significant curling at the low PRF, rotation about its axis with occasional curling at the moderate PRF, and localized vibration at the high PRF due to the generation of acoustic radiation force and streaming. Quantitative analysis of recorded motion shows the axial displacement decreases with the PRF of delivered HIFU bursts, from 3.9+/-1.5mm at 1Hz to 0.7+/-0.4mm at 1000Hz. Bubble cavitation during HIFU exposure to the blood clot was also monitored. The increase of PRF led to the increase of inertial cavitation but the decrease of stable cavitation. In summary, the PRF of delivered HIFU bursts at the same output energy has a significant effect on the thrombi motion, bubble cavitation activities, and subsequently thrombolysis efficiencies. PMID- 27666198 TI - Nagashima-type palmoplantar keratosis in a Chinese Han population. AB - Nagashima-type palmoplantar keratosis (NPPK) is an autosomal recessive form of palmoplantar keratoderma (PPK), which is caused by mutations in the SERPINB7 gene. NPPK has only been reported in Japanese and Chinese populations. The present study was conducted on 12 unrelated Chinese patients who were clinically predicted to suffer from NPPK. Mutation screening was performed by direct sequencing of the entire coding regions of SERPINB7, SLURP1, AQP5, CSTA, KRT1 and KRT9 genes. Direct sequencing of SERPINB7 revealed five homozygous founder mutations (c.796C>T) and four compound heterozygous mutations in nine patients, including one novel mutation (c.122_127delTGGTCC). Nine out of the 12 patients were diagnosed with NPPK due to SERPINB7 pathogenic mutations, and the results expanded the known mutation spectrum of NPPK. Taking the other seven reported Chinese patients, who had been definitively diagnosed with NPPK by genetic testing, into account, the present study further demonstrated that NPPK is a common entity in Mainland China, and c.796C>T is the most prevalent mutation and exerts a founder effect. Furthermore, the NPPK cases described in the current study presented a consistently mild phenotype, as compared with the degrees of phenotypic variability associated with other types of relatively severe PPK, including Mal de Meleda and Olmsted syndrome. PMID- 27666199 TI - Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments. AB - Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy. PMID- 27666200 TI - Abrupt switch to migratory night flight in a wild migratory songbird. AB - Every year, billions of wild diurnal songbirds migrate at night. To do so, they shift their daily rhythm from diurnality to nocturnality. In captivity this is observed as a gradual transition of daytime activity developing into nocturnal activity, but how wild birds prepare their daily rhythms for migration remains largely unknown. Using an automated radio-telemetry system, we compared activity patterns of free-living migrant and resident European blackbirds (Turdus merula) in a partially migratory population during the pre-migratory season. We found that activity patterns between migrant and resident birds did not differ during day and night. Migrants did not change their daily rhythm in a progressive manner as has been observed in captivity, but instead abruptly became active during the night of departure. The rapid shift in rhythmicity might be more common across migratory songbird species, but may not have been observed before in wild animals due to a lack of technology. PMID- 27666203 TI - Plans for 'prompt'complaints procedure welcomed by RCN. AB - The Royal College of Nursing has warmly welcomed government plans to streamline the system of dealing with complaints about the health service. PMID- 27666202 TI - Editorial. AB - Clinical supervision is the latest trend to hit nursing. Although the concept is not new - in fact psychotherapy, counselling and social work have all developed a degree of clinical supervision - it is still a relative newcomer to nursing practice. Clinical supervision, not to be confused with mentorship or preceptorship, is concerned with all nurses, junior to senior. Whether this new fad will last is questionable, but all the right people are seemingly behind it. PMID- 27666201 TI - Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation. AB - Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10, generates similar lesions as MC. Interstrand cross-links (ICLs) are believed to be the lesions primarily responsible for the cytotoxicity of MC and DMC. The major ICL generated by MC (alpha-ICL) has a trans stereochemistry at the guanine-drug linkage whereas the major ICL from DMC (beta-ICL) has the opposite, cis, stereochemistry. In addition, DMC can provoke strong p53 independent cell death. Our hypothesis is that the stereochemistry of the major unique beta-ICL generated by DMC is responsible for this p53-independent cell death signaling. p53 gene is inactively mutated in more than half of human cancers. p21WAF1/CIP1 known as a major effector of p53 is involved in p53 dependent and -independent control of cell proliferation and death. This study revealed the role of p21WAF1/CIP1 on MC and DMC triggered cell damage. MCF-7 (p53 proficient) and K562 (p53-deficient) cells were used. Cell cycle distributions were shifted to the G1/S phase in MCF-7 treated with MC and DMC, but were shifted to the S phase in K562. p21WAF1/CIP1 activation was observed in both cells treated with MC and DMC, and DMC triggered more significant activation. Knocking down p53 in MCF-7 did not attenuate MC and DMC induced p21WAF1/CIP1 activation. The alpha-ICL itself was enough to cause p21WAF1/CIP1 activation. PMID- 27666204 TI - Management crisis erupts at UKCC. AB - UK Central Council President Mary Uprichard has called in an outside personnel consultant to help resolve a major rift between Registrar Colin Ralph and disaffected senior staff. PMID- 27666205 TI - Nurses pay tribute to John Smith. AB - England's Chief Nursing Officer has paid tribute to Labour Party leader John Smith, who died last week. PMID- 27666206 TI - Value of nursing research questioned. AB - A leading medical professor has publicly questioned whether there is 'such a thing as nursing research'. PMID- 27666208 TI - Sister Prophit goes public alleging anti-catholic vendetta. AB - Sister Penny Prophit has defended herself publicly for the first time against allegations of academic fraud and suggestions that she failed to declare her friendship with a Scottish Office official who was involved in the award of research grants totalling more than L1 million. PMID- 27666207 TI - International nurses' day. AB - Nurses across the country and around the world joined forces to celebrate International Nurses' Day last Thursday, the 154th anniversary of the birth of Florence Nightingale. PMID- 27666210 TI - Midwifery advisory group announced. AB - Members of an advisory group to support the implementation of the 'Changing Childbirth' report u-ere announced last week. PMID- 27666212 TI - Study shows women care more about health. AB - Women are far more likely than men to get health information from practice nurses and health visitors according to a new report by the Office of Health Economics (OHE). PMID- 27666211 TI - Nurses suspended over payphone fraud allegations. AB - Four nurses have been suspended for allegedly making thousands of pounds worth of private telephone calls. PMID- 27666213 TI - ? AB - Above: RCN headquarters was decorated with flags from countries across Europe to mark International Nurses' Day last week. Among the guests were scriptwriters from the BBC series Casualty. Left: Healthy Families for Healthy Nations was the theme of a Health Fair staged by nurses in Islington Above left: Nurse Fay Peyton at a service in Westminster Abbey to commemorate the life of Florence Nightingale. Similar services were held for the first time in Scotland, Wales and Northern Ireland. PMID- 27666215 TI - Welsh trust's letter confirms job losses to fund pay award. AB - Welsh secretary John Redwood has been warned the 3 per cent pay award to nurses can only be met by axing posts. PMID- 27666214 TI - Supervision would benefit all nurses. AB - Nurses should be fully involved in planning and introducing systems of clinical supervision, a report published last week by the influential think-tank the King's Fund argues. Clinical supervision should be clearly defined with all staff before it is introduced in any unit, it says. PMID- 27666216 TI - Nurses in shock after morphine mix-up. AB - Shocked nurses at a Lanarkshire Trust hospital have received counselling after an incident where the wrong patient was injected with a massive dose of morphine. PMID- 27666218 TI - Campaign sets new standards for breast cancer sufferers. AB - A major initiative to provide practical help for women with breast cancer was launched this week after a survey revealed standards of treatment vary dramatically across the country. PMID- 27666217 TI - ? AB - Shopping list: Sheffield Labour MP and Shadow Health Secretary David Blunkett added his name to a nurses' petition to save local A&E departments when they collected signatures in the city centre recently. The event was organised by the Sheffield RCN Branch. Mr Blunkett is pictured with RCN Branch Secretary' Maureen Haslam. PMID- 27666219 TI - Report reveals 'age restrictions' do exist. AB - Elderly patients are being discriminated against by the NHS according to a report published last week by the Royal College of Physicians. PMID- 27666220 TI - ? AB - A room of my own: The Royal College of Nursing recently opened; room where visitors can feed and change babies at its Cavendish Square headquarters in London. Among the first to use the room were Susan Thorpe and her son Cameron. PMID- 27666221 TI - Health visitors 'under threat'. AB - The role of health visitors has been jeopardised by the introduction of GP fundholding, the MSF union conference in Brighton heard last week. PMID- 27666223 TI - ? AB - The trauma of having to undergo surgery can be devastating for children, according to new guidelines published by Action for Sick Children. Among the 13 standards set out in the report is a recommendation that all surgery' on children should be undertaken by surgeons and anaesthetists with appropriate training and experience. Pictured left, Mahmuda Sultan, eight, has her treatment explained by nurse Virginia Wong after her operation at the Royal London Hospital, Whitechapel. PMID- 27666222 TI - Health care workers still afraid to speak up. AB - Freedom of speech does not exist within the NHS, the union MSF warned at its annual conference last week. PMID- 27666225 TI - Report demands greater safety with blood transfusions. AB - A national system for reporting critical blood transfusion incidents should be set up, the Scottish National Blood Transfusion Service hits demanded. PMID- 27666227 TI - Disabled young need special sex lessons. AB - Young disabled people are in need of sex education specifically linked to their needs, a leading researcher has argued. PMID- 27666228 TI - Smoking hastens diabetic nephropathy. AB - Smoking speeds up the progression of diabetic nephropathy, new research from Germany suggests. PMID- 27666226 TI - HRT without menstruation launching in the UK soon. AB - A new form of HRT which avoids menstrual bleeding may help to cut the large numbers of women who stop taking therapy within a year of starting. PMID- 27666229 TI - Easier radiotherapy shielding with putty. AB - Shielding healthy tissue during radiation treatment for malignant disease might be easier thanks to a new material developed by American researchers. PMID- 27666230 TI - Eczema risk increases with social class. AB - Eczema is more prevalent in children of social classes I and II than in lower social classes, London researchers report. PMID- 27666231 TI - Differences in medicines might prove a hazard. AB - An Oxford pharmacologist says that if people buy a product labelled Anadin they might reasonably expect all formulations to be the same. It takes a high degree of awareness to realise that Anadin contains aspirin and caffeine while Anadin Extra contains aspirin, caffeine and paracetamol. And Anadin is only one of many examples. PMID- 27666232 TI - Leadership sought in mental health. AB - A new pilot scheme to develop excellence in mental health leadership has been launched, backed by the RCN, the Institute of Health Service Management and the Government. PMID- 27666233 TI - Disability awareness for clinical staff. AB - 'Smell me,' said the sister to the blind patient. 'Then you'll know who I am next time we meet.' PMID- 27666234 TI - Rare beast spotted in Bournemouth. AB - While attending RCN Congress in Bournemouth recently, I was intrigued to come into contact with a new form of species which Darwin had unwittingly omitted, namely clinicalus supervisisorus, commonly known as clinical supervision. PMID- 27666235 TI - Should we change nursing's structure? AB - The editorial of May 4 states that the nursing profession 'was caught unaware by the intensity of the movement towards lowering the qualified staffing levels'. PMID- 27666237 TI - Built-in antidotes are not the solution. AB - The Consumers' Association's call for paracetamol combined with an antidote is, unfortunately, not only based on false premise but is also misguided (More painkillers with built-in antidote could reduce overdose risks, study says, Clinical news, April 13). PMID- 27666236 TI - Another view of patient focused care. AB - In her article, 'Patient focused care without the upheaval' (Features, April 13), Sue Johnson expresses views which are contrary to our understanding of the patient focused care (PFC) concept. PMID- 27666238 TI - There's an art to passing on bad news. AB - I was saddened by the heading on the article, 'Bad news, I'm afraid' (Viewpoint, May 4). I did not get the message from the article that doctors are so bad. The more important message was the steps to address this, and suggestions for a way forward. PMID- 27666239 TI - Information exchange. AB - * I am a Project 2000 student nurse and have been searching for information on the use of eggs from aborted foetuses in fertility treatment, recently banned by Parliament. My group is currently engaged in a debate on the issue. would also be interested to hear what the RCN thinks about it. PMID- 27666241 TI - FPA Contraceptive Handbook FPA Contraceptive Handbook T Belfield Family Planning Association 164pp L12.99 0-90.3289-7706. AB - The FPA Contraceptive Handbook is up-to-date, concise, comprehensive, accurate and easy-to-read. The list of contents is clear; chapter headings provide specific information on the text; and the text itself is attractively laid out. Line drawings and diagrams are used to good effect. PMID- 27666240 TI - Food combining for vegetarians Food combining for vegetarians J Le Tissier Thorsons 272pp L4.99 0-7225-2763-2. AB - Food combining is a healthy way of eating which separates starch from protein and increases the quantity of alkaline foods in your daily diet. The system was devised by Dr William Howard I lay, who concluded that freedom from disease lay not in relieving symptoms but in treating underlying causes. PMID- 27666242 TI - Mental health and mental illness, 5th edition Mental health and mental illness, 5th edition P D Barry J B Lippincott 438pp L24.95 0-397-55013-8. AB - If you are planning to work in the USA, Mental Health and Mental Illness is the book for you. It is clear and concise, covering cost implications, insurance, ANA guidelines on nursing practice, and offers a simple explanation of the categories of nursing diagnosis as laid down by the North American Nursing Diagnostic Association. PMID- 27666243 TI - Cutting costs or cutting corners? AB - The problem of pressure sore development has been well documented for many years but the last decade has witnessed an explosion in the pressure sore prevention industry accompanied by a rise in pressure sore prevention policy. PMID- 27666244 TI - Study results on pressure area care. AB - Patients receive just over 45 minutes each day of pressure area care, a study of nursing activities has revealed. PMID- 27666245 TI - Alternating pressure overlays give best results in clinical trials. AB - A study of alternating pressure overlays has shown they reduce pressure by about 60 per cent compared with standard hospital mattresses. PMID- 27666247 TI - Inadequate use of cushions criticised. AB - Wheelchair users are in constant danger of pressure sores because of inadequate use of pressure relief cushions, a leading biomechanic has warned. PMID- 27666246 TI - Patients at risk not identified. AB - Many patients at risk of pressure sores are not being seen by district nurses, a survey has revealed. PMID- 27666249 TI - Products & information. AB - ? A device to prevent pressure sores in the urethra and bladder neck has been developed by a clinical nurse specialist. Known as WISSC (Waistband with Integral Support Strap for Catheters), it was designed by Peter Lowthian to prevent sores developing following long-term catheter use. PMID- 27666248 TI - Risk in theatre. AB - A pilot study has confirmed that the position of patients on operating tables does contribute to pressure sore development. PMID- 27666250 TI - Strategy to test clinical guidelines on pressure sores. AB - The NHS Executive is supporting the start of three implementation strategies at the end of May to test its clinical guidelines on the prevention and management of pressure sores. PMID- 27666251 TI - Association launched at australian conference. AB - The second international wound management conference to be held in Australia within two years attracted a wide range of speakers from Europe, the US and Australia. PMID- 27666252 TI - Changing faces: two years on. AB - Reconstructive plastic surgery and medicine have made great strides in recent years. Advances mean that scarring, evidence of injury, and various abnormalities can be reduced in conspicuousness and sometimes even removed, for example, the use of laser treatment for port wine stains. Contrary to the Hollywood myth, however, in which people involved in horrific accidents are restored to their former glory, plastic surgery is not a 'miracle cure'. Disfigurement is rarely temporary: most are left disfigured for life. PMID- 27666253 TI - Drake Medox discusses the benefits of working for an agency. AB - Drake Medox Nursing Agency has been established in London since 1978 and has built itself an enviable reputation as one of London's most prestigious agencies providing its client hospitals with qualified staff of a very high standard. As part of the world wide Drake International organisation it has offices all over the world including Canada and Australia. PMID- 27666254 TI - London nurses agency limited. AB - The staff at London Nurses Agency are looking forward to meeting you. PMID- 27666255 TI - Lpns sets the standard. AB - LPNS provides temporary nurses throughout the healthcare sector. PMID- 27666256 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Miking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Pax: 081-423 3867. PMID- 27666257 TI - Introduction to "Diversity of Child Health Care in Europe: A Study of the European Paediatric Association/Union of National European Paediatric Societies and Associations". AB - The field of pediatrics in Europe is characterized by the diversities, variations, and heterogeneities of child health care services provided in 53 European countries with more than 200 million children below 18 years of age. Managing the health care of infants, children, and adolescents in Europe requires balancing clinical aims, research findings, and socioeconomic goals within a typical environment characterized by cultural and economic complexity and large disparity in availability, affordability, and accessibility of pediatric care. Since its foundation in 1976, the European Paediatric Association-Union of National European Paediatric Societies and Associations has worked to improve both medical care of all children and cooperation of their caretakers in Europe. Such a report has been conceived in the strong belief that broadening of the intellectual basis of the European Paediatric Association-Union of National European Paediatric Societies and Associations and creating a multidisciplinary society will be necessary to reduce fragmentation of pediatrics and tackle the legal, economic, and organizational challenges of child health care in Europe. PMID- 27666258 TI - Child Health Care in Israel. AB - Israel is a relatively rapidly growing country with a high fertility rate and a young population. These data emphasize the importance of an efficient and appropriate pediatric service for its population. Although the pediatric service in Israel has attained several achievements, such as a relatively low infant mortality, high vaccination rates, and a primary care service that is mainly based on licensed pediatricians, several challenges, such as overcoming inequalities in health care and health indices between different regions and different populations within the country and the provision of a more organized mental and dental health care service to children, need to be addressed. PMID- 27666259 TI - Maternal and Child Health Care Services in Albania. AB - Albania has one of the youngest populations among the European countries. Albania continues to be involved in a progressive improvement of standards for the protection and respect of children's rights to health. We describe the Albanian pediatric health system, with a particular focus on pediatric primary health care and, first access care, and the structure and staffing of health centers and women and children's consulting centers. Secondary and tertiary pediatric care and neonatal care are also described. The Albanian national laws approved during recent years have had a positive impact on the status of women and children; however, the outcomes seem to be insufficient because of the persistence of several negative socioeconomic factors. The Albanian Pediatric Society believes that the important and beneficial changes observed during the last 20 years should be further supported and implemented. In this regard, Albanian Pediatric Society is fully committed to developing initiatives described in this report and to join the efforts of international collaborative programs and studies aimed at improving the social and health conditions of Albanian children. PMID- 27666260 TI - The Child Health Care System in Italy. AB - Pediatric care in Italy has been based during the last 40 years on the increased awareness of the importance of meeting the psychosocial and developmental needs of children and of the role of families in promoting the health and well-being of their children. The pediatric health care system in Italy is part of the national health system. It is made up of 3 main levels of intervention: first access/primary care, secondary care/hospital care, and tertiary care based on specialty hospital care. This overview will also include a brief report on neonatal care, pediatric preventive health care, health service accreditation programs, and postgraduate training in pediatrics. The quality of the Italian child health care system is now considered to be in serious danger because of the restriction of investments in public health caused both by the 2008 global and national economic crisis and by a reduction of the pediatric workforce as a result of progressively insufficient replacement of specialists in pediatrics. PMID- 27666261 TI - The Child Health Care System of Macedonia. AB - Macedonia is a multiethnic developing country with a new democratic political system in transition from a former communist country. The country gained independence as former Yugoslav Republic of Macedonia in 1991. Recent health reforms have privatized pediatric primary care and introduced family doctors alongside primary care pediatricians. Increasing privatization of hospitals have left the state-run hospitals short of pediatric specialists and subspecialists as doctors moved to private hospitals for better salaries and working conditions. There is little coordinated action between the Ministry of Health, health insurance fund, and Macedonian pediatricians to overcome the problems that now exist within the pediatric/child health system because of these recent reforms, which were politically driven without consultation with the Macedonian Pediatric Association. These recent decisions will have an adverse effect on the quality of care for children and families, which will likely continue for another 5-10 years. PMID- 27666262 TI - Preventive Child Health Care within the Framework of the Dutch Health Care System. AB - The Netherlands has established a high quality system of child health care based on a unique standardized digital preventive child health program underpinned by legislation. Stringent assessment of the implementation of the new Youth Act is needed to fulfill the United Nations' child rights to health. The impact of national child health care systems on the well-being of children with long-term conditions should be evaluated by using international (World Health Organization) comparable coding to document the benefit of preventive child health care programs and their outcomes. PMID- 27666263 TI - Child Health in Portugal. AB - Portugal has experienced rapid decline of neonatal and infant mortality in the last century, similar to that of other western European states. The joint venture of pediatricians and obstetricians with adequate top-down government commissions for maternal and child health for the decision making by health administrators and a well-defined schedule of preventive and managerial measures in the community and in hospitals are the most likely explanations for this success. Another achievement of child health care services is the registry for special diseases. Education of health care workers plays a fundamental role in improving health statistics. Portugal has a reasonable number of doctors, nurses, and health technicians per capita. Quality assurance monitoring systems and implementation of evidence-based clinical guidelines with digital records, including international coding, are essential steps to improve health care systems. PMID- 27666264 TI - The Russian Child Health Care System. AB - We present a historical and analytical overview of the Russian child health care system describing strengths and challenges of the system. Main indicators of social environment and children's health, general demographics, and socioeconomic factors of Russia are described. The Russian health care system has preserved positive elements of the former Soviet model of pediatric care. However, beginning in 1991, it has been altered greatly in its funding and management. The child health care system is composed of a special network of outpatient and inpatient facilities. The key element of pediatric community care is the pediatric polyclinic, staffed by district pediatricians and nurses. Undergraduate pediatric training is separate from adult medical training. From day one onward, future pediatricians are trained at separate pediatric faculties of universities. Thus, they qualify as general pediatricians after only 2 years of postgraduate training. It should be emphasized that the gap between the health status of children in developed countries and the Russian Federation is largely due to the influence of socioeconomic determinants, such as traffic accidents, poverty, pollution, and hazardous life styles, including binge drinking. Further improvements of children's health require protective measures by the state to address the underlying socioeconomic determinants. PMID- 27666265 TI - The Child Health Care System of Serbia. AB - The health care system in Serbia is based on a network of public health institutions funded by the National Health Insurance and from the state budget. Access to public health institutions is free. Preventive and curative services are provided at the local level in primary health care centers. Over the past 5-7 years, the number of pediatricians in primary health care centers decreased because of reduced number of applicants for pediatric training, which endangers the maintenance of the traditional model of pediatric care. Secondary medical care is offered in pediatric departments of local and regional general hospitals or outpatient clinics, and in specialized hospitals for children or adults. Tertiary medical care is provided by inpatient or outpatient subspecialty services in 5 major university children's clinics. The health reforms undertaken in the recent 10 years have aimed at strengthening preventive health care and reducing the overall costs for pediatric care. Current initiatives of the Ministry of Health and national pediatric associations are aimed at reestablishing and strengthening the capacity of the primary pediatric health care model by increasing the number of physicians and developing new processes of care. PMID- 27666266 TI - Health Care System for Children and Adolescents in Slovenia. AB - Slovenia's health system is financed by a Bismarckian type of social insurance system with a single insurer for a statutory health insurance, which is fully regulated by national legislation and administered by the Health Insurance Institute of Slovenia. The health insurance system is mandatory, providing almost universal coverage (98.5% of the population). Children and adolescents have the right to compulsory health insurance as family members of an insured person until the end of their regular education. Slovenia has a lower number of physicians per capita than both the European Union and the Central and Eastern Europe countries. Slovenia is facing a workforce crisis, as the number of health professionals retiring is not adequately being replaced by new trainees. There is also a net deficit of nurses with university and college degrees. Physicians working with children and adolescents in primary level have a 5-year specialization in pediatrics. Slovenia tends to be in line with the goals for the development of pediatric health care on a primary level in European countries, which are to maintain the achieved level of quality, better and equitable access, and delivery of services, aiming to reduce inequalities in health of children and adolescents and provide for every child and adolescent in the best way possible. PMID- 27666267 TI - Child Health Systems in Sweden. AB - On a national level, several factors are responsible for Sweden's leading position in achieving the excellent health of children because Sweden has experienced a long history of peace and success in establishing a parliamentary democracy throughout the 20th century. Among the different sectors of society, Sweden has been able to focus on prevention and health promotion. The Swedish health care system is publicly financed based on local taxation. Pediatricians working in secondary and tertiary care are employed by the public sector, whereas family physicians are employed by both the private and public sectors. The pediatric departments at county and university levels provide a high quality of inpatient care for neonates and children. The county hospital pediatric departments typically include one neonatal ward and one ward for older children. Subspecialization exists even at the county level, and there is close cooperation between the county level and subspecialist units at the university level. Within the primary care sector, most children receive care from family physicians. The majority of family physicians have completed 3 months of pediatrics in their basic training program. In the more densely populated areas there are also pediatric ambulatory care centers working mostly with referrals from the family physicians. Preventive care is carried out at midwife-led maternity health centers, nurse-led Child Health Centers, and nurse-led school health care settings and reach almost everyone (99%). All health care for children and adolescents is free of charge up to 18 years of age. PMID- 27666268 TI - Child Health Care in Switzerland. AB - We provide an overview of Swiss child health care, describe the organizational structures of primary care services and hospital care in pediatrics, and analyze such significant challenges as the decline of the number of primary care physicians in communities and the economic and regulatory pressures on hospitals. We also offer thoughts and ideas for future directions, initiatives, and innovations to ensure that each child achieves the best possible health and quality of life, which is the ultimate goal of health care professionals. New developments should be promoted from a position of strength because Swiss pediatrics is well positioned, and its future remains bright. PMID- 27666270 TI - An Overview on Child Health Care in Turkey. AB - The general health status of the Turkish people has improved significantly in recent years. Improvements in the health status of the child population followed the introduction of health reforms, such as the Health Transformation Program. Presently, Turkey is undergoing further important changes concerning its medical system. The changes introduced during 2005-2015 have provided almost complete health insurance coverage and increased accessibility to primary health care givers. However, health providers realize that there are ongoing inefficiencies and deficiencies in both the health care system and health education. There is a need for continuous improvement; challenges lie ahead for improving services beyond primary care. The main criticism of previous health care reforms has come mainly from professionals in the health care sector because of their privileged position as inside observers being able to analyze pros and cons of the system. Quality and sustainability of future reform programs will rely not only on the economic support of the public health and health care sector, but also on the high standards of service pathways and satisfaction of both patients and providers of care by multifactorial quality assurance and continuous quality improvement analyses of basic elements of health care. PMID- 27666269 TI - Child and Adolescent Health in Armenia: Experiences and Learned Lessons. AB - The health of children and adolescents of Armenia has been affected by various socioeconomic, environmental, educational, and behavioral factors, demonstrating trends typical for both developed and developing countries. Key issues to be addressed by Armenian pediatricians are child mortality, malnutrition, and growth failure in the early years and overweight in later years. The case of Armenia illustrates how countries in transition are currently tackling both "old" problems (mortality and malnutrition) and "new" emerging morbidities (chronic diseases and adolescent health problems) based on social and health determinants, but the financing of the health system is far from satisfactory. Lessons of Armenia indicate the need for more cooperation between general practitioners and pediatricians at a primary care level. In addition, a better balance between inpatient and outpatient care could be achieved, which is not yet the case. Nevertheless, the overall performance of the Armenian child health care system can be considered satisfactory when bearing in mind the limitation of resources. Among the successful factors are those inherited from the Soviet period health system, including key institutions such as rural health posts and health centers, city polyclinics, and hospitals. These institutions mostly meet the needs of Armenian children and families today. PMID- 27666271 TI - Child Health Systems in the United Kingdom (England). AB - Child health in the United Kingdom has improved markedly over recent decades but has failed to match health gains and reductions in mortality achieved by other European countries. Child poverty and inequalities are rising in the United Kingdom. The National Health Service (NHS) is a universally accessible health service, funded by taxation and is free at the point of use. The NHS is undergoing substantial reform, aiming to improve care quality and experience, meet rising demands, and contain costs. The NHS is struggling to balance access with expertise for urgent and unscheduled care. There is increasing use of urgent and emergency care, and there are unexplained variations in outcomes. Quality of care for children and young people with chronic and long-term conditions, including transition services, is variable and sometimes poor. Many determinants of noncommunicable conditions are worsening. Key achievements include a universal service free at the point of use, providing generally accessible, and equitable care. Key challenges include increasing fragmentation of services, insufficient emphasis on preventive care, achieving an effective balance between access and expertise of care for children, and improving child health and well-being outcomes despite generally high quality inputs and high levels of spending. PMID- 27666272 TI - Child Health Care Services in Austria. AB - We describe child health care in Austria, a small country in Central Europe with a population of about 9 million inhabitants of whom approximately 1.7 million are children and adolescents under the age of 20 years. For children and adolescents, few health care indicators are available. Pediatric and adolescent health provision, such as overall health provision, follows a complex system with responsibilities shared by the Ministry of Health, 19 social insurance funds, provinces, and other key players. Several institutions are affiliated with or cooperate with the Ministry of Health to assure quality control. The Austrian public health care system is financed through a combination of income-based social insurance payments and taxes. Pediatric primary health care in Austria involves the services of general pediatricians and general practitioners. Secondary care is mostly provided by the 43 children's hospitals; tertiary care is (particularly) provided in 4 state university hospitals and 1 private university hospital. The training program of residents takes 6 years and is completed by a final examination. Every year, this training program is completed by about 60 residents. PMID- 27666273 TI - The Child Health Care System of Croatia. AB - The Republic of Croatia is a Parliamentary Republic with a population of 4.2 million people that sits on the Adriatic coast within Central Europe. Gross domestic product is approximately 60% of the European Union average, which in turn, limits health service spending. The health system is funded through universal health insurance administered by the Croatian Health Insurance Fund based on the principles of social solidarity and reciprocity. The children of Croatia are guaranteed access to universal primary, hospital, and specialist care provided by a network of health institutions. Pediatricians and school medicine specialists provide comprehensive preventive health care for both preschool and school-aged children. Despite the Croatian War of Independence in the late 20th century, indicators of child health and measures of health service delivery to children and families are steadily improving. However, similar to many European countries, Croatia is experiencing a rise in the "new morbidities" and is responding to these new challenges through a whole society approach to promote healthy lifestyles and insure good quality of life for children. PMID- 27666274 TI - Short Review of Child Health Care in Former Czechoslovakia and Czech Republic since 1993. AB - We provide an overview on child health care in Czech Republic, including a historical background. Child health care has substantially improved in Czech hospitals during the past 20 years. Eight pediatric departments are located in university hospitals. The technical background of pediatric services meets high international standards. Inpatient and outpatient care is offered on a 24-hour service, and all pediatric subspecialties are usually provided. The different pediatric subspecialties are organized in the frame of the Czech Pediatric Society, and all of them have developed dynamic international scientific collaborations. From the organizational point of view, the formation of specialized centers of competence at university departments of pediatrics followed a mixture of a "bottom-up and top-down strategy" of all opinion and decision makers. PMID- 27666275 TI - The Child Health System in Denmark: Current Problems and Successes. AB - In Denmark, child primary care is taken care of by general practitioners who have 6 months of pediatric training as part of their specialty training and, therefore, are qualified to work as gatekeepers for the secondary health care at the hospitals. As new, more expensive, drugs are increasingly prescribed, corresponding expenses pose serious threats to the economy at 18 pediatric departments. We will highlight the new developments in pediatric education: skills training and training of clinical reasoning. PMID- 27666276 TI - Health Services and Well-Being of Children in Estonia. AB - Estonia has a population of 1.3 million, which makes it one of the least populous member states of the European Union. The fertility rate was 1.65 in 2011, and the average age of women at first child birth was 4 years higher than in the early 1990s. Medical care is free for all children in Estonia. For the last 20 years, family doctors have been responsible for the primary care of children. Pediatric subspecialists work mainly in 2 children's hospitals: the Children's Clinic of Tartu University Hospital and Tallinn Children's Hospital. The average duration of hospital stay has decreased year by year. Pediatric subspecialists take care of children with long-term conditions and chronic diseases. In recent years, electronic case reports and digital receipts have been in use in Estonia. New diagnostic tests and expensive medications, which are available, make the cost of medical care very high. PMID- 27666277 TI - Child Health Care in Georgia. AB - We summarize the pediatric health care system in Georgia. In the 1990s, the socialist health insurance system was abandoned and replaced by a private health insurance system. In general, Georgia has a relatively high number of physicians per capita, and there are 3 times as many physicians per unit of population in Tbilisi than in other region. Furthermore, the country's universities produce far more physicians than needed. Currently, there are approximately 3000 pediatricians. The Georgian National Center of Disease Control provides guidelines for early detection and screening of diseases, immunization, and mother and child health care. Although Georgia has a limited health budget, it has performed major health reforms. It aims at achieving the highest possible standard of care for children with chronic and disabling conditions, however, future development will depend on the access to more advanced diagnostic and therapeutic technologies. PMID- 27666278 TI - The Child Health Care System of Germany. AB - We describe the strengths and challenges of the child health care system in Germany and also provide an outlook on future health plans, focusing on making idiosyncrasies of national health care services in Europe understandable to those pediatricians working in other countries. The aim should be to avoid those unnecessary processes in child care which, unless abandoned, may be responsible for a poor outcome of child health. Larger countries, such as Germany, have many distinct regional differences. When it comes to problem-solving strategies, pediatricians must be aware of unavoidable cultural and historic differences that may influence the outcome of care. Even when assuming unlimited financial resources, different regional priorities might result in diverging goals. PMID- 27666279 TI - Child Health Care in Ireland. AB - The Irish health care system is based on a complex and costly mix of private, statutory, and voluntary provisions. The majority of health care expenditure comes from the state, with a significant proportion of acute hospital care funded from private insurance, but there are relatively high out-of-pocket costs for most service users. There is free access to acute hospital care, but not for primary care, for all children. About 40% of the population have free access to primary care. Universal preventive public health services, including vaccination and immunization, newborn blood spot screening, and universal neonatal hearing screening are free. Major health challenges include poverty, obesity, drug and alcohol use, and mental health. The health care system has been dominated for the last 5 years by the impact of the current recession, which has led to very sharp cuts in health care expenditure. It is unclear if the necessary substantial reform of the system will happen. Government policy calls for a move toward a patient-centered, primary care-led system, but without very substantial transfers of resources and investment in Information and Communication Technology, this is unlikely to occur. PMID- 27666281 TI - Corrigendum: The Expression of Human Cytomegalovirus MicroRNA MiR-UL148D during Latent Infection in Primary Myeloid Cells Inhibits Activin A-triggered Secretion of IL-6. PMID- 27666280 TI - Mesoporous Silica Supported Pd-MnOx Catalysts with Excellent Catalytic Activity in Room-Temperature Formic Acid Decomposition. AB - For the application of formic acid as a liquid organic hydrogen carrier, development of efficient catalysts for dehydrogenation of formic acid is a challenging topic, and most studies have so far focused on the composition of metals and supports, the size effect of metal nanoparticles, and surface chemistry of supports. Another influential factor is highly desired to overcome the current limitation of heterogeneous catalysis for formic acid decomposition. Here, we first investigated the effect of support pore structure on formic acid decomposition performance at room temperature by using mesoporous silica materials with different pore structures such as KIE-6, MCM-41, and SBA-15, and achieved the excellent catalytic activity (TOF: 593 h-1) by only controlling the pore structure of mesoporous silica supports. In addition, we demonstrated that 3D interconnected pore structure of mesoporous silica supports is more favorable to the mass transfer than 2D cylindrical mesopore structure, and the better mass transfer provides higher catalytic activity in formic acid decomposition. If the pore morphology of catalytic supports such as 3D wormhole or 2D cylinder is identical, large pore size combined with high pore volume is a crucial factor to achieve high catalytic performance. PMID- 27666282 TI - Accuracy of the Distress Thermometer for home care patients with palliative care needs in Germany. AB - OBJECTIVE: Our aim was to examine the accuracy of the German version of the Distress Thermometer (DT) compared with the Hospital Anxiety and Depression Scale (HADS) in patients with palliative care needs living at home. METHOD: Ours was a 15-month cross-sectional study beginning in September of 2013 in Germany with consecutive patients cared for by a palliative home care service. The survey was implemented during the initial visit by a home care team. Patients were excluded if they were under 18 years of age, mentally or physically unable to complete the assessment questionnaires as judged by their healthcare worker, or unable to understand the German language. During the first encounter, the DT and HADS were applied, and sociodemographic and medical data were collected. RESULTS: A total of 89 persons completed both the HADS and DT questionnaires (response rate = 59.7%; mean age = 67 years; female = 55.1%; married = 65.2%; living home with relatives = 73.0%; oncological condition = 92.1%; Karnofsky Performance Scale [KPS] score: 0-40 = 30.3%, 50-70 = 57.3%, >80 = 6.7%). The mean DT score was 6.3 (+/-2.3), with 84.3% of participants scoring above the DT cutoff (>=4). The mean HADStotal score was 17.9 (+/-7.8), where 64% of participants had a total HADS score (HADStotal) >=15, 51.7% reported anxiety (HADSanxiety >= 8), and 73% reported depression (HADSdepression >= 8). Using the HADS as a gold standard, a DT cutoff score >=5 was optimal for identifying severe distress in patients with palliative care needs, with a sensitivity of 93.0%, a specificity of 34.4%, a positive predictive value (PPV) of 73.3%, and likelihood ratios LR+ = 1.42 (<3) and -LR = 0.203 (<0.3). SIGNIFICANCE OF RESULTS: The DT performed satisfactorily compared to the HADS in screening for distress in our study and can be employed as an instrument for identification of patients with distress. Consequent to the high prevalence of distress, we recommend its routine use for screening distressed persons at home with palliative care needs in order to offer adequate support. PMID- 27666283 TI - Acquired hemophilia A in a patient with hepatocellular carcinoma: a case report and literature review. PMID- 27666285 TI - Inappropriate Clostridium difficile Testing and Consequent Overtreatment and Inaccurate Publicly Reported Metrics. AB - BACKGROUND The nationally reported metric for Clostridium difficile infection (CDI) relies solely on laboratory testing, which can result in overreporting due to asymptomatic C. difficile colonization. OBJECTIVE To review the clinical scenarios of cases of healthcare facility-onset CDI (HO-CDI) and to determine the appropriateness of C. difficile testing on the basis of presence of symptomatic diarrhea in order to identify areas for improvement. DESIGN Retrospective cohort study. SETTING Northwestern Memorial Hospital, a large, tertiary academic hospital in Chicago, Illinois. PATIENTS The cohort included all patients with a positive C. difficile test result who were reported to the National Healthcare Safety Network as HO-CDI during a 1-year study period. METHODS We reviewed the clinical scenario of each HO-CDI case. On the basis of documentation and predefined criteria, appropriateness of C. difficile testing was determined; cases were deemed appropriate, inappropriate, or indeterminate. Statistical analysis was performed to compare demographic and clinical parameters among the categories of testing appropriateness. RESULTS Our facility reported 168 HO-CDI cases to NHSN during the study period. Of 168 cases, 33 (19.6%) were judged to be appropriate tests, 25 (14.8%) were considered inappropriate, and 110 (65.5%) were indeterminate. Elimination of inappropriate testing would have improved our facility's standardized infection ratio from 0.962 to 0.819. CONCLUSION Approximately 15% of HO-CDI cases were judged to be tested inappropriately. Testing only patients with clinically significant diarrhea would more accurately estimate CDI incidence, reduce unnecessary antibiotic use, and improve facilities' performance of reportable CDI metrics. Improved documentation could facilitate targeted interventions. Infect Control Hosp Epidemiol 2016;1395-1400. PMID- 27666287 TI - Energetic potential of algal biomass from high-rate algal ponds for the production of solid biofuels. AB - In this investigation, chemical characteristics, higher, lower and net heating value, bulk and energy density, and thermogravimetric analysis were applied to study the thermal characteristics of three algal biomasses. These biomasses, grown as by-products of wastewater treatment in high-rate algal ponds (HRAPs), were: (i) biomass produced in domestic effluent and collected directly from an HRAP (PO); (ii) biomass produced in domestic effluent in a mixed pond-panel system and collected from the panels (PA); and (iii) biomass originating from the treatment effluent from the meat processing industry and collected directly from an HRAP (IN). The biomass IN was the best alternative for thermal power generation. Subsequently, a mixture of the algal biomasses and Jatropha epicarp was used to produce briquettes containing 0%, 25%, 50%, 75%, and 100% of algal biomass, and their properties were evaluated. In general, the addition of algal biomass to briquettes decreased both the hygroscopicity and fixed carbon content and increased the bulk density, ash content, and energy density. A 50% proportion of biomass IN was found to be the best raw material for producing briquettes. Therefore, the production of briquettes consisting of algal biomass and Jatropha epicarp at a laboratory scale was shown to be technically feasible. PMID- 27666284 TI - Influence of the watch and wait strategy on clinical outcomes of patients with follicular lymphoma in the rituximab era. AB - We analyzed the effects of the initial approach to patients with follicular lymphoma (FL) on outcomes in order to investigate whether the watch and wait (WW) strategy is still an acceptable approach in the rituximab era. We retrospectively analyzed 348 patients who were initially diagnosed with FL between 2000 and 2012. We compared the clinical outcomes of the WW cohort and immediate treatment cohort. Among 348 patients (median age of 57 years, range: 19-85), 101 were initially managed with WW and 247 were immediately treated. The median follow-up duration was 75 months (range: 7-169). The estimated median time to treatment failure (TTF) in the treatment following WW cohort and immediate treatment cohort were 92 months (95 % CI, 60.1-NA) and 77 months (95 % CI, 65.1-107.6), respectively, which were not significantly different (P = 0.272) . In a multivariate analysis, clinical stage was identified as a predictive factor of TTF (HR 1.19, 95 % CI, 1.03-1.38, P < 0.05). Neither overall survival rate nor cumulative risk of transformation between the WW cohort and immediate treatment cohort was significant. The results of the present study suggested that the WW strategy is still an acceptable approach for selected FL patients in the rituximab era. PMID- 27666288 TI - The H2/CH4 ratio during serpentinization cannot reliably identify biological signatures. AB - Serpentinization potentially contributes to the origin and evolution of life during early history of the Earth. Serpentinization produces molecular hydrogen (H2) that can be utilized by microorganisms to gain metabolic energy. Methane can be formed through reactions between molecular hydrogen and oxidized carbon (e.g., carbon dioxide) or through biotic processes. A simple criterion, the H2/CH4 ratio, has been proposed to differentiate abiotic from biotic methane, with values approximately larger than 40 for abiotic methane and values of <40 for biotic methane. The definition of the criterion was based on two serpentinization experiments at 200 degrees C and 0.3 kbar. However, it is not clear whether the criterion is applicable at a wider range of temperatures. In this study, we performed sixteen experiments at 311-500 degrees C and 3.0 kbar using natural ground peridotite. Our results demonstrate that the H2/CH4 ratios strongly depend on temperature. At 311 degrees C and 3.0 kbar, the H2/CH4 ratios ranged from 58 to 2,120, much greater than the critical value of 40. By contrast, at 400-500 degrees C, the H2/CH4 ratios were much lower, ranging from 0.1 to 8.2. The results of this study suggest that the H2/CH4 ratios cannot reliably discriminate abiotic from biotic methane. PMID- 27666286 TI - Clock Genes in Glia Cells: A Rhythmic History. AB - Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes' transcription, collectively known as "clock-controlled genes." Several brain regions other than the SCN express circadian rhythms of clock genes, including the amygdala, the olfactory bulb, the retina, and the cerebellum. Glia cells in these structures are expected to participate in rhythmicity. However, only certain types of glia cells may be called "glial clocks," since they express PER-based circadian oscillators, which depend of the SCN for their synchronization. This contribution summarizes the current information about clock genes in glia cells, their plausible role as oscillators and their medical implications. PMID- 27666289 TI - Increased plasma/serum levels of prolactin in systemic lupus erythematosus: a systematic review and meta-analysis. AB - BACKGROUND: Prolactin (PRL), a polypeptide hormone produced by the pituitary gland, is involved in the regulation of humoral and cell mediated immune responses. PRL levels have been investigated in several autoimmune diseases including systemic lupus erythematosus (SLE), however, yielded different and inconsistent results. This study aims to derive a more precise evaluation on plasma/serum PRL levels in SLE patients, as well as the potential influential factors. METHODS: Studies published from 1 January 1987 to 31 December 2015 in English, which comparing plasma/serum PRL levels between SLE group and control group were searched in PubMed, EMBASE and The Cochrane Library databases. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I2, publication bias was evaluated using a funnel plot and Egger's linear regression test. RESULTS: Five hundred and forty-seven articles were obtained after searching databases, and 12 studies with 429 SLE patients and 326 controls were finally included. Meta analysis revealed that, compared with the control group, the SLE group had significantly higher plasma/serum PRL levels (P < 0.001), with the SMD of 1.26 and 95%CI (0.70,1.82). Subgroup analyses showed that SLE patients from Asia and Europe had higher plasma/serum PRL levels. However, no significant change in plasma/serum PRL levels was observed in SLE patients from America (P > 0.05). CONCLUSIONS: Overall, our study suggests that SLE patients have higher plasma/serum PRL level, but with a regional difference. PMID- 27666290 TI - Multi-functional nano silver: A novel disruptive and theranostic agent for pathogenic organisms in real-time. AB - The present study was aimed at evaluating the fluorescence property, sporicidal potency against Bacillus and Clostridium endospores, and surface disinfecting ability of biogenic nano silver. The nano silver was synthesized using an actinobacterial cell-filtrate. The fluorescence property as well as imaging facilitator potency of this nano silver was verified adopting spectrofluorometer along with fluorescent and confocal laser scanning microscope wherein strong emission and bright green fluorescence, respectively, on the entire spore surface was observed. Subsequently, the endospores of B. subtilis, B. cereus, B. amyloliquefaciens, C. perfringens and C. difficile were treated with physical sporicides, chemical sporicides and nano silver, in which the nano silver brought about pronounced inhibition even at a very low concentration. Finally, the environmental surface-sanitizing potency of nano silver was investigated adopting cage co-contamination assay, wherein vital organs of mice exposed to the nano silver-treated cage did not show any signs of pathological lesions, thus signifying the ability of nano silver to completely disinfect the spore or reduce the count required for infection. Taken these observations together, we have shown the multi-functional biological properties of the nano silver, synthesized using an actinobacterial cell-filtrate, which could be of application in advanced diagnostics, biomedical engineering and therapeutics in the near future. PMID- 27666292 TI - Magnetic moment collapse induced axial alternative compressibility of Cr2TiAlC2 at 420 GPa from first principle. AB - The electronic structure and thermodynamical properties of Cr2TiAlC2 are studied by first principles under pressure. The obtained results observed that the ferromagnetic order is the most stable ground state and the magnetic moment will collapse at about 50 GPa. As a result, the lattice a axis becomes stiffer above about 420 GPa, ultimately presenting the same axial compressibility trends with those of nonmagnetic compounds Mo2TiAlC2 and hypothetical Cr2TiAlC2. The elastic constants and phonon dispersion curves demonstrate the structural stability during the disappearance of magnetic moment and occurrence of axial alternative compressibility. The density of states and energy band calculations confirmed the existence of magnetic moment of Cr2TiAlC2 at 0 GPa and disappearance at high pressures above 50 GPa. Evolutions of magnetic moment collapse with pressure are confirmed by a variety of properties. The obtained gruneisen parameter and thermal expansion coefficients show the maximum value among the known MAX phases, to date and to the author's knowledge. PMID- 27666293 TI - Management of CSF leak in base of skull fractures in adults. AB - AIMS: CSF leaks are not uncommon after a base of skull fracture. Currently there is no standardised algorithm for the investigation and management of post traumatic CSF leaks. In this paper we aim to provide an evidence-based framework for managing post-traumatic CSF leaks. METHODS: We searched the English literature over the past 45 years using CINAHL, EMBASE and MEDLINE for the terms (1) post-traumatic CSF leaks or fistulas, and (2) basilar or base of skull fractures, but excluded papers on post-operative and non-traumatic CSF leaks, and papers on paediatric post- traumatic CSF leaks. RESULTS: The diagnosis of a base of skull fracture and any resultant CSF leak can be challenging. Therefore a combination of biochemical and radiological studies are needed to optimise the diagnosis of this condition. Post-traumatic CSF leaks are generally treated conservatively, and a majority of them resolve without further surgical management. However for patients who are refractory to such treatments, surgical closure of the CSF fistula is necessary. Surgical obliteration of CSF leaks can be challenging and requires the involvement of multiple surgical specialties such as neurosurgery, otolaryngology, and maxillofacial surgery. CONCLUSION: Although we have formulated a simple algorithm to aid the investigation and management of post-traumatic CSF leaks, there are still many important unresolved questions requiring further well powered studies to answer. PMID- 27666291 TI - Integrating Multi-omics Data to Dissect Mechanisms of DNA repair Dysregulation in Breast Cancer. AB - DNA repair genes and pathways that are transcriptionally dysregulated in cancer provide the first line of evidence for the altered DNA repair status in tumours, and hence have been explored intensively as a source for biomarker discovery. The molecular mechanisms underlying DNA repair dysregulation, however, have not been systematically investigated in any cancer type. In this study, we performed a statistical analysis to dissect the roles of DNA copy number alteration (CNA), DNA methylation (DM) at gene promoter regions and the expression changes of transcription factors (TFs) in the differential expression of individual DNA repair genes in normal versus tumour breast samples. These gene-level results were summarised at pathway level to assess whether different DNA repair pathways are affected in distinct manners. Our results suggest that CNA and expression changes of TFs are major causes of DNA repair dysregulation in breast cancer, and that a subset of the identified TFs may exert global impacts on the dysregulation of multiple repair pathways. Our work hence provides novel insights into DNA repair dysregulation in breast cancer. These insights improve our understanding of the molecular basis of the DNA repair biomarkers identified thus far, and have potential to inform future biomarker discovery. PMID- 27666294 TI - Effective vitrification and warming of porcine embryos using a pH-stable, chemically defined medium. AB - The use of pH-stable media would simplify embryo vitrification and the warming of porcine embryos and might facilitate the application of embryo transfer in practice. In this work, we investigated whether a pH-stable basal medium constituted of Tyrode's lactate medium, polyvinyl alcohol, and HEPES for buffering was suitable for porcine embryo vitrification warming in place of the conventional gas-equilibrated media. A high percentage (>90%) of embryos survived vitrification and warming in this medium, achieving in vitro survival rates similar to embryos vitrified-warmed using the conventional protocol and their fresh counterparts. The pH-stable medium did not affect the in vivo developmental competence of the vitrified-warmed embryos. A farrowing rate of 71.4% (5/7) with 10.4 +/- 3.1 piglets born was obtained for the embryos vitrified and warmed in this medium and transferred to selected recipients. This medium will enable the use of simple, safe and standardized protocols for the vitrification and warming of porcine embryos for optimal embryo survival and quality when applied under field conditions. This study opens new possibilities for the widespread use of embryo transfer in pigs. PMID- 27666295 TI - Effectiveness of UV-C light irradiation on disinfection of an eSOS((r)) smart toilet evaluated in a temporary settlement in the Philippines. AB - Ultraviolet germicidal (short wavelength UV-C) light was studied as surface disinfectant in an Emergency Sanitation Operation System((r)) smart toilet to aid to the work of manual cleaning. The UV-C light was installed and regulated as a self-cleaning feature of the toilet, which automatically irradiate after each toilet use. Two experimental phases were conducted i.e. preparatory phase consists of tests under laboratory conditions and field testing phase. The laboratory UV test indicated that irradiation for 10 min with medium-low intensity of 0.15-0.4 W/m(2) could achieve 6.5 log removal of Escherichia coli. Field testing of the toilet under real usage found that UV-C irradiation was capable to inactivate total coliform at toilet surfaces within 167-cm distance from the UV-C lamp (UV-C dose between 1.88 and 2.74 mW). UV-C irradiation is most effective with the support of effective manual cleaning. Application of UV-C for surface disinfection in emergency toilets could potentially reduce public health risks. PMID- 27666296 TI - Spot-checks to measure general hygiene practice. AB - A variety of hygiene behaviors are fundamental to the prevention of diarrhea. We used spot-checks in a survey of 761 households in Burundi to examine whether something we could call general hygiene practice is responsible for more specific hygiene behaviors, ranging from handwashing to sweeping the floor. Using structural equation modeling, we showed that clusters of hygiene behavior, such as primary caregivers' cleanliness and household cleanliness, explained the spot check findings well. Within our model, general hygiene practice as overall concept explained the more specific clusters of hygiene behavior well. Furthermore, the higher general hygiene practice, the more likely children were to be categorized healthy (r = 0.46). General hygiene practice was correlated with commitment to hygiene (r = 0.52), indicating a strong association to psychosocial determinants. The results show that different hygiene behaviors co occur regularly. Using spot-checks, the general hygiene practice of a household can be rated quickly and easily. PMID- 27666299 TI - Therapeutic management of bone metastasis in prostate cancer: an update. AB - INTRODUCTION: Bone metastases affect the majority of patients with castration resistant prostate cancer (CRPC), resulting in significant morbidity and mortality. This review describes the current therapies available for the management of CRPC patients with bone metastases. Areas covered: Studies on the use of currently available therapeutic approaches for palliating pain, delaying skeletal-related events (SREs) and prolonging survival in CRPC patients with bone metastases have been examined. PubMed database was searched in May 2016 starting with the following keywords: ('castration-resistant prostate cancer' OR 'CRPC') AND 'bone metastases', and approximately 270 results were retrieved. More specific searches were then performed on the epidemiology and molecular pathogenesis (in particular, 'vicious cycle' was used as a keyword), the management of pain, SREs and survival. The following keywords were also used individually: abiraterone, cabazitaxel, denosumab, docetaxel, enzalutamide, radium-223, sipuleucel-T, samarium-153, strontium-89, zoledronate. Randomized controlled trials, observational studies, reviews, systematic reviews and meta analyses were selected and articles were excluded if not in English. Expert commentary: Currently, clear recommendations on the optimal use of the agents available to treat mCRPC are lacking. Therefore, to ensure patients the best treatment, both their clinical characteristics and the features of each product have to be considered. PMID- 27666297 TI - Fine particulate matter (PM2.5) association with peripheral artery disease admissions in northeastern United States. AB - BACKGROUND: Current evidence, on the association of PM2.5 and peripheral artery disease (PAD) is very sparse. METHODS: We use novel PM2.5 prediction models to investigate associations between chronic and acute PM2.5 exposures and hospital PAD admissions across the northeast USA. Poisson regression analysis was preformed where daily admission counts in each zip code are regressed against both chronic and acute PM2.5 exposure, temperature, socio-economic characteristics and time to control for seasonal patterns. RESULTS: Positive significant associations were observed between both chronic and acute exposure to PM2.5 and PAD hospitalizations. Every 10-MUg/m(3) increase in acute PM2.5 exposure was associated with a 0.26 % increase in admissions (CI = 0.08 - 0.45 %) and every 10-MUg/m(3) increase in chronic PM 2.5 exposure was associated with a 4.4 % increase in admissions (CI = 3.50 - 5.35 %). CONCLUSIONS: The study supports the hypothesis that acute and chronic exposure to PM2.5 can increase the risk of PAD. PMID- 27666300 TI - We all stand together. PMID- 27666301 TI - Bringing 'forgiveness' into the International Classification for Nursing Practice. PMID- 27666302 TI - Supporting a good life and death in residential aged care: an exploration of service use towards end of life. AB - BACKGROUND: The concept of a 'good death' involves end-of-life care in an appropriate setting and in keeping with the person's preferences. Limited research has examined the circumstances and place of death for older people living in residential aged care. OBJECTIVE: This exploratory study investigated the nature of health service use and place of death of older people living in aged care to identify factors that lead to transfer of end-of-life care to other settings and poorer outcomes. METHODS: Retrospective review of residential aged care client records between July 2014 and June 2015. CONCLUSION: The majority of people in this study died in their home setting of residential care and a number were in receipt of palliative care prior to their deaths. The study proposes a national approach to the use of terminology and documents related to palliative and end-of-life care and education in assessment and recognition of nearing the end of life. PMID- 27666303 TI - Improving end-of-life care through quality improvement. AB - Although end of life (EoL) care has been identified as an area for quality improvement in hospitals, the quality of care Canadian patients receive at the end of life is not well-evidenced. National statistics indicate that Canadians would prefer to die at home, yet more than 50% die in acute care hospital settings. Busy and often highly specialised acute care units may be perceived as a distressing place of death for both patients and their families. Furthermore, many clinicians are not trained in diagnosing imminent dying, managing symptoms at the end of life or supporting dying patients and their families. As such, to improve the experience of EoL care, a corporate, institution-wide strategy entitled the Quality Dying Initiative was introduced and implemented across a tertiary care academic teaching hospital. A primary focus of this initiative was the implementation of a comprehensive Comfort Measures Strategy. This strategy involved the development of an evidence-based order set, which included elements of symptom assessment and management, patient and family education, and spiritual and emotional support. Staff education and mentoring was also a critical element of the larger Comfort Measures Strategy, as well as an evaluative component. PMID- 27666304 TI - An assessment of palliative care beliefs and knowledge: the healthcare provider's perspective. AB - Research shows that healthcare providers' palliative care training and their misconceptions impact the delivery of care. As a result, the need for continuing education with adequate training is paramount to improve their knowledge and confidence in addressing the needs of patients and families facing serious illnesses. A pre-experimental static-group comparison design was used to determine if there was a significant difference in perceived competency and knowledge between healthcare providers who participated in a palliative care training programme and those who did not. A non-randomised sample of healthcare providers were administered a questionnaire to assess perceived competence and knowledge. Responses from 388 participants revealed a significant association between perceived competency and knowledge scores. The authors concluded that participation in a palliative care programme makes a significant difference in the healthcare provider's knowledge. However, further exploration is necessary to deduce the underlying reason for the negative association between perceived competency and knowledge. PMID- 27666306 TI - Experiences of healthcare professionals as caregivers of a dying family member: an exploratory study. AB - BACKGROUND: Many health-care professionals also take on a caregiver role at home, usually by caring for a dying relative. Very little is known about the perceptions, experiences and needs of this specific group of carers. OBJECTIVE: To understand the perceptions and experiences of healthcare professionals as caregivers and identify their needs. METHODS: Health-care professionals working at one health unit in Portugal participated in a semi-structured interview (n=9). Data were analysed and organised thematically. RESULTS: Four key themes emerged from the analysis: (i) the perception of the caregiver role, (ii) the difficulties experienced in the caregiver role, (iii) the rewards obtained by carrying out the caregiver role and (iv) the healthcare professional's needs as a caregiver. CONCLUSION: Healthcare professionals' needs as caregivers are not assessed and addressed holistically, creating room for improvement. Participants felt emotionally pressured by their families to get answers and find solutions during caregiving. Despite it being a complex and painful process, participants still gave examples of rewards experienced during caregiving. PMID- 27666305 TI - Screening for delirium in specialist palliative care inpatient units: perceptions and outcomes. AB - OBJECTIVES: The UK National Institute for Health and Care Excellence (NICE) indicate that palliative care patients are at high risk of delirium and should be screened for it using the short confusion assessment method (short CAM). This study aimed to assess the perceptions of the short CAM for delirium screening amongst health-care workers in specialist palliative care inpatient units (SPCUs) and to investigate its use as a screening instrument. METHODS: Patients in 5 SPCUs in the North East of England were screened for delirium using the short CAM and a staff survey assessed the acceptability of the short-CAM in this setting. RESULTS: Of the 63 staff surveyed, 79.4% felt screening for delirium was important and 59.3% found the short CAM 'not at all' burdensome to complete. However, only 40.7% felt that the short-CAM often accurately reflected patients' conditions and none felt it always accurately reflected patients' condition. Of 298 patients screened, 20% screened positive on the short CAM. Malignant and intra-cerebral diseases were significant independent predictors of a positive screen. Hospice length of stay and in-hospice mortality were higher in those with a positive result (66.7%) than in those without (38.2%). CONCLUSIONS: Health professionals deem delirium screening to be important in SPCUs, but may not support routine use of the short CAM. This could reflect a limited perceived impact on care and lack of confidence in this tool to reflect a complex patient group. PMID- 27666307 TI - What are the barriers to initiating end-of-life conversations with patients in the last year of life? AB - INTRODUCTION: Improving end of life care is a national imperative. Unsatisfactory care persists particularly in acute hospitals, with shortcomings, variability in communication and advance care planning identified as fundamental issues. This review explored the literature to identify what is known about the barriers to initiating end-of-life conversations with patients from the perspective of doctors and nurses in the acute hospital setting. METHOD: Six electronic databases were searched for potentially relevant records published between 2008 and 2015. Studies were included if the authors reported on barriers to discussing end of life with families or patients as described by doctors or nurses in hospital settings, excluding critical care. RESULTS: Of 1267 potentially relevant records, 12 were included in the review. Although there is limited high-quality evidence available, several barriers were identified. Recurrent themes within the literature related to a lack of education and training, difficulty in prognostication, cultural differences and perceived reluctance of the patient or family. CONCLUSIONS: This study illustrated that, in addressing barriers to communication, consideration needs to be extended to include how to embed good communication practice between patients and health professionals into the culture of this setting. Board level commitment is required to raise awareness of, and familiarity with, policies and protocols concerning communication and end-of-life care. Communication training should include practical skills and tools, opportunities to explore the personal beliefs of practitioners and managing their emotions, opportunities to analyse the local organisational (physical and social environment) and team barriers. PMID- 27666308 TI - Research roundup. AB - Synopses of a selection of recently published research articles of relevance to palliative care. PMID- 27666309 TI - Politics and palliative care: Niger. AB - Dion Smyth's review of the internet for palliative nursing. PMID- 27666311 TI - Surface magnetism of strontium titanate. AB - SrTiO3 plays a central role in oxide electronics. It is the substrate of choice for functional oxide heterostructures based on perovskite-structure thin-film stacks, and its surface or interface with a polar oxide such as LaAlO3 can become a 2D conductor because of electronic reconstruction or the presence of oxygen defects. Inconsistent reports of magnetic order in SrTiO3 abound in the literature. Here, we report a systematic experimental study aimed at establishing how and when SrTiO3 can develop a magnetic moment at room temperature. Polished (1 0 0), (1 1 0) or (1 1 1) crystal slices from four different suppliers are characterized before and after vacuum annealing at 750 degrees C, both in single crystal and powdered form. Impurity content is analysed at the surface and in the bulk. Besides the underlying intrinsic diamagnetism of SrTiO3, magnetic signals are of three types-a Curie law susceptibility due to dilute magnetic impurities at the ppm level, a hysteretic temperature-dependent ferromagnetic impurity contribution, and a practically anhysteretic defect-related temperature independent component that saturates in about 200 mT. The latter component is intrinsic. It is often the largest, reaching 10 MU B nm-2 of the surface area or more and dominating the magnetic response in low fields at room temperature. It is associated with defects near the surface, and can be destroyed by treatment with Tiron (C6H4Na2O8S2), an electron donor molecule that forms a strong complex with titanium at the surface. The origin of this unusual high-temperature ferromagnetic-like response is discussed. PMID- 27666310 TI - RNAi-mediated downregulation of cyclin Y to attenuate human breast cancer cell growth. AB - Cyclin Y (CCNY) is a newly identified PFTK1 interacting protein and has been found to be associated with the proliferation and tumorigenesis of human non small cell lung cancer. In the present study, we analyzed the expression levels of CCNY in 65 cases of breast cancer (BC) tissues and in four BC cell lines, BT 474, MDA-MB-231, T-47D and MCF-7. Lentivirus-mediated short hairpin RNA (shRNA) was employed to knock down CCNY expression in MCF-7 and MDA-MB-231 cells. The effects of CCNY depletion on cell growth were examined by MTT, colony formation and flow cytometry assays. The results showed that immunohistochemical expression of CCNY in tumor tissues is stronger than that in normal tissues. CCNY was also expressed in all four BC cells. The knockdown of CCNY resulted in a significant reduction in cell proliferation and colony formation ability. Cell cycle analysis showed that CCNY knockdown arrested MDA-MB-231 cells in the G0/G1 phase. Furthermore, depletion of CCNY inhibited BC cell growth via the activation of Bad and GSK3beta, as well as cleavages of PARP and caspase-3 in a p53-dependent manner. Therefore, we believe that CCNY has biological effect in BC development, and its inhibition via an RNA interference lentiviral system may provide a therapeutic option for BC. PMID- 27666312 TI - Corynebacterium crudilactis sp. nov., isolated from raw cow's milk. AB - A Gram-stain-positive, rod-shaped bacterium (strain JZ16T) was isolated from raw cow's milk from the bulk tank of a dairy farm in Germany. The 16S rRNA gene sequence of the isolate showed a similarity of 98.3 % to the nearest related type strain Corynebacterium glutamicum ATCC 13032T, a similarity of 97.6 % to Corynebacterium deserti GIMN1.010T and a similarity of 97.4 % to Corynebacterium callunae DSM 20147T. Determination of chemotaxonomic characteristics revealed oleic acid (18 : 1 cis 9) as the predominant fatty acid, major amounts of hexadecanoic acid (16 : 0) and minor amounts of heptadecanoic acid (17 : 0). The isolate showed an acetyl type of peptidoglycan and corynemycolic acids. The menaquinones MK-8(H2) and MK-9(H2) and the phospholipids diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside were detected, which was in agreement with the description of the genus Corynebacterium. Strain JZ16T was positive for reduction of nitrate to nitrite, pyrazinamidase, beta-glucuronidase, beta-glucosidase and urease activities. Acid was produced from d-glucose, d-ribose and d-mannitol, but not from d-xylose, maltose, lactose, sucrose and glycogen. The results of phylogenetic, phenotypic and chemotaxonomic analyses enabled the differentiation of the isolated strain from other closely related species of the genus Corynebacterium. Therefore, strain JZ16T represents a novel species of the genus Corynebacterium, for which the name Corynebacterium crudilactis sp. nov. is proposed. The type strain is JZ16T (=DSM 100882T=CCUG 69192T=LMG 29813T). PMID- 27666313 TI - Phylogenetic diversity, antimicrobial susceptibility and virulence characteristics of phylogroup F Escherichia coli in Australia. AB - Unlike Escherichia coli strains belonging to phylogroup B2, the clinical significance of strains belonging to phylogroup F is not well understood. Here we report on a collection of phylogroup F strains recovered in Australia from faeces and extra-intestinal sites from humans, companion animals and native animals, as well as from poultry meat and water samples. The distribution of sequence types was clearly non-random with respect to isolate source. The antimicrobial resistance and virulence trait profiles also varied with the sequence type of the isolate. Phylogroup F strains tended to lack the virulence traits typically associated with phylogroup B2 strains responsible for extra-intestinal infection in humans. Resistance to fluoroquinolones and/or expanded-spectrum cephalosporins was common within ST648, ST354 and ST3711. Although ST354 and ST3711 are part of the same clonal complex, the ST3711 isolates were only recovered from native birds being cared for in a single wildlife rehabilitation centre, whereas the ST354 isolates were from faeces and extra-intestinal sites of dogs and humans, as well as from poultry meat. Although ST354 isolates from chicken meat in Western Australia were distinct from all other ST354 isolates, those from poultry meat samples collected in eastern Australia shared many similarities with other ST354 isolates from humans and companion animals. PMID- 27666314 TI - Aqueous-Solid System for Highly Efficient and Environmentally Friendly Transphosphatidylation Catalyzed by Phospholipase D To Produce Phosphatidylserine. AB - The purely aqueous system of phospholipase D (PLD)-mediated transphosphatidylation using pre-existing carriers for the adsorption of phosphatidylcholine (PC) to act as an "artificial interface" was introduced to replace the liquid-liquid system. Toxic organic solvents are avoided during the reaction, and the free enzyme can be simply reused by centrifugation. Special attention has been paid to the effect of the pore diameter and surface area of silica gel 60H covered with PC molecules on the yield of phosphatidylserine (PS). Results indicated that the highest PS yield of 99.5% was achieved. Moreover, 73.6% of the yield of PS was obtained after being used for six batches. This is the first description of the remarkably high reusability of free enzymes for enzymatic synthesis of PS as well. The excellent results make the aqueous-solid system more promising candidates for the industrial production of PS. PMID- 27666315 TI - Selection and validation of miRNAs as normalizers for profiling expression of microRNAs isolated from thyroid fine needle aspiration smears. AB - Fine needle aspiration cytology (FNAC) is currently the method of choice for malignancy prediction in thyroid nodules. Nevertheless, in some cases the interpretation of FNAC results may be problematic due to limitations of the method. The expression level of some microRNAs changes with the development of thyroid tumors, and its quantitation can be used to refine the FNAC results. For this quantitation to be reliable, the obtained data must be adequately normalized. Currently, no reference genes are universally recognized for quantitative assessments of microRNAs in thyroid nodules. The aim of the present study was the selection and validation of such reference genes. Expression of 800 microRNAs in 5 paired samples of thyroid surgical material corresponding to different histotypes of tumors was analyzed using Nanostring technology and four of these (hsa-miR-151a-3p, -197-3p, -99a-5p and -214-3p) with the relatively low variation coefficient were selected. The possibility of use of the selected microRNAs and their combination as references was estimated by RT-qPCR on a sampling of cytological smears: benign (n=226), atypia of undetermined significance (n=9), suspicious for follicular neoplasm (n=61), suspicious for malignancy (n=19), medullary thyroid carcinoma (MTC) (n=32), papillary thyroid carcinoma (PTC) (n=54) and non-diagnostic material (ND) (n=34). In order to assess the expression stability of the references, geNorm algorithm was used. The maximum stability was observed for the normalization factor obtained by the combination of all 4 microRNAs. Further validation of the complex normalizer and individual selected microRNAs was performed using 5 different classification methods on 3 groups of FNAC smears from the analyzed batch: benign neoplasms, MTC and PTC. In all cases, the use of the complex classifier resulted in the reduced number of errors. On using the complex microRNA normalizer, the decision-tree method C4.5 makes it possible to distinguish between malignant and benign thyroid neoplasms in cytological smears with high overall accuracy (>91%). PMID- 27666316 TI - Direct-write nanoscale printing of nanogranular tunnelling strain sensors for sub micrometre cantilevers. AB - The sensitivity and detection speed of cantilever-based mechanical sensors increases drastically through size reduction. The need for such increased performance for high-speed nanocharacterization and bio-sensing, drives their sub micrometre miniaturization in a variety of research fields. However, existing detection methods of the cantilever motion do not scale down easily, prohibiting further increase in the sensitivity and detection speed. Here we report a nanomechanical sensor readout based on electron co-tunnelling through a nanogranular metal. The sensors can be deposited with lateral dimensions down to tens of nm, allowing the readout of nanoscale cantilevers without constraints on their size, geometry or material. By modifying the inter-granular tunnel-coupling strength, the sensors' conductivity can be tuned by up to four orders of magnitude, to optimize their performance. We show that the nanoscale printed sensors are functional on 500 nm wide cantilevers and that their sensitivity is suited even for demanding applications such as atomic force microscopy. PMID- 27666317 TI - Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation. AB - Hypoxic or near-anoxic conditions that occur in the core of transplanted islets induce necrosis and apoptosis during the early stages after transplantation, primarily due to loss of vascularization during the isolation process. Moreover, secretion of various cytokines from pancreatic islets is detrimental to the viability of islet cells in vitro. In this study, we aimed to protect pancreatic islet cells against apoptosis by establishing a method for in situ delivery of curcumin to the pancreatic islets. Self-assembled heterospheroids composed of pancreatic islet cells and curcumin-loaded polymeric microspheres were prepared by the three-dimensional cell culture technique. Release of curcumin in the microenvironment of pancreatic islets promoted survival of the islets. In hypoxic culture conditions, which mimic the in vivo conditions after transplantation, viability of the islets was significantly improved, as indicated by a decreased expression of pro-apoptotic protein and an increased expression of anti-apoptotic protein. Additionally, oxidative stress-induced cell death was suppressed. Thus, unlike co-transplantation of pancreatic islets and free microspheres, which provided a wide distribution of microspheres throughout the transplanted area, the heterospheroid transplantation resulted in colocalization of pancreatic islet cells and microspheres, thereby exerting beneficial effects on the cells. PMID- 27666318 TI - Very Long-Lived Photoinduced Charge-Separated States of Triphenylamine Naphthalenediimide Dyads in Polymer Matrices. AB - Photoinduced electron transfer was studied in dyads (dyad1 and dyad2) containing triphenylamine (MTA) and naphthalenediimide (MNDI) linked with oligo(phenyleneethynylene) dispersed in rigid polymer matrices of polystyrene (PS), poly(vinyl chloride), and poly(methyl methacrylate). Photoexcitation of these dyads yielded long-lived charge-separated (CS) states involving MTA+ and MNDI-. The quantum yields of charge separation in dyad1 and dyad2 were approximately 0.4 and 0.3, respectively, in the polymer matrices. The CS lifetime for dyad2 in PS was longer (400 ms) than those in poly(vinyl chloride) (120 ms) and poly(methyl methacrylate) (65 ms) at 298 K. In addition, CS state had a very long lifetime of 5.4 s in glassy toluene at 100 K. Below glass transition temperatures, polymer side chain motions with various relaxation rates should affect the charge recombination processes. The energy gap (DeltaG) and outer sphere reorganization energy (lambda) in the charge recombination process were estimated using a slow-frequency component for dielectric constants. By use of DeltaG and lambda values, the matrix dependence of the CS lifetimes was successfully rationalized based on Marcus theory, and the charge recombination process in PS with low polarity and high polarizability should be in a deeper inverted region than the other polymer matrices. It also suggested that the rigidity of the polymer effectively suppressed intramolecular motions promoting the charge recombination process. PMID- 27666319 TI - Transport Dynamics of Neutral Excitons and Trions in Monolayer WS2. AB - Understanding the spatial motion of excitons is of both fundamental interest and central importance for optoelectrical applications. Here, we have investigated the temperature (T) dependence of the transport dynamics of neutral excitons and charged excitons (trions) in atomically thin two-dimensional crystals of the transition-metal dichalcogenide WS2. The transport dynamics of neutral excitons can be divided into three temperature ranges, where the diffusion of neutral excitons is governed by thermal activation (<=~75 K), ionized impurity scattering (~75 K <= T <=~200 K), and LO phonon scattering (>=~200 K). The trions have a diffusion length that is over 20 times longer than that of neutral excitons at very low temperatures (<=~10 K), which may be related to theoretically predicted Pauli-blocking effects during the excitation process. PMID- 27666320 TI - Posterior Reversible Encephalopathy Syndrome in a pregnant patient: a PRESsing matter. PMID- 27666321 TI - Diagnostic work-up of patients presenting in primary care with lower abdominal symptoms: which faecal test and triage strategy should be used? AB - Bowel endoscopy referrals from primary care have increased steadily over recent years. However, most patients do not have significant colorectal disease (SCD). Therefore, strategies to select those who would benefit most from endoscopy are of current interest. A recent study developed a multivariable diagnostic model for SCD with routine clinical information, extended with quantitative faecal calprotectin (f-C) point-of-care (POC) testing and/or qualitative POC faecal immunochemical test (FIT) for haemoglobin (f-Hb) results. This study used POC tests for both f-C and f-Hb; however, POC tests have many disadvantages and there are several reasons why quantitative measurements of f-Hb are advantageous. Quantitative faecal immunochemical tests have been used very successfully in triage of patients presenting in primary care as a rule-out test. Studies have compared f-C and f-Hb in this clinical context and consider that f-C is not required in diagnosis. A single quantitative f-Hb result, without any clinical information, could be sufficient to decide whom to refer for endoscopy and, because of the significant overlap of symptoms in those with and without SCD, could be the primary investigation performed.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0684-5 . PMID- 27666323 TI - Complement component C1q as potential diagnostic but not predictive marker of preeclampsia. AB - PROBLEM: We have previously found that C1q is constitutively expressed by invading trophoblast and endothelial cells of decidua and contributes to vascular and tissue remodeling. Based on these findings, we sought to determine whether there were changes in the circulating level of C1q that may be used as a diagnostic and predictive marker of preeclampsia. METHOD OF STUDY: We measured the levels of C1q, C4, and complement activation products in serum or plasma of normal pregnant women and preeclamptic patients from different cohorts. RESULTS: We observed a marked decrease in the concentration of C1q associated with a reduced level of C4 in preeclamptic patients as compared to matched healthy pregnant woman but no significant difference in the circulating level of the activating products C5a and the soluble terminal complement complex sC5b-9. Analysis of serum samples collected at early phase of pregnancy from women who later developed preeclampsia failed to show a decrease in C1q level. CONCLUSION: The results of the present investigation demonstrate that low levels of C1q and C4 are associated with preeclampsia but cannot be used as predictive markers. PMID- 27666322 TI - Polysaccharide isolated from the liquid culture broth of Inonotus obliquus suppresses invasion of B16-F10 melanoma cells via AKT/NF-kappaB signaling pathway. AB - A number of polysaccharides exhibit pharmacological activities. Polysaccharides derived from Inonotus obliquus (PLIO) appear to have various potential pharmacological properties, including anti-tumor activity. However, the molecular mechanisms underlying these properties remain to be elucidated. The present study investigated the anti-metastatic potential of PLIO and the underlying signaling pathways in B16-F10 murine melanoma cells using the MTT colorimetric assay, in vitro migration and invasion assays, and flow cytometric and western blot analyses. PLIO inhibited the invasion of B16-F10 cells and suppressed the expression of matrix metalloproteinases. PLIO treatment inhibited nuclear factor kappaB (NF-kappaB) nuclear translocation in B16-F10 cells. In addition, PLIO treatment inhibited the phosphorylation of c-Jun N-terminal kinases and AKT. These results suggest that PLIO may suppress the invasion of highly metastatic melanoma cells via inhibition of the AKT/NF-kappaB signaling pathways. PMID- 27666324 TI - Prenatal exposure to persistent organic pollutants in association with offspring neuropsychological development at 4years of age: The Rhea mother-child cohort, Crete, Greece. AB - BACKGROUND: Persistent Organic Pollutants (POPs) are highly-resistant compounds to environmental degradation and due to fat solubility they bioaccumulate through the food chain. As they cross the placenta, in utero exposure to POPs could disrupt child neurodevelopment as they are considered to be neurotoxic. AIMS: We examined whether in utero exposure to levels of different POPs is associated with offspring cognitive and behavioral outcomes at 4years of age in a mother-child cohort in Crete, Greece (Rhea study). METHODS: We included 689 mother-child pairs. Concentrations of several polychlorinated biphenyls (PCBs) and other organochlorine compounds (dichlorodiphenyl dichloroethene [DDE], hexachlorobenzene [HCB]) were determined in maternal serum collected in the first trimester of pregnancy by triple quadrupole mass spectrometry. Neurodevelopment at 4years was assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for potential confounders. RESULTS: Children with "high" HCB concentrations (>=90th percentile) in maternal serum, demonstrated decreased scores in perceptual performance (adjusted beta=-6.07; 95% CI: -10.17, 1.97), general cognitive (adjusted beta=-4.97; 95% CI: -8.99, -0.96), executive function (adjusted beta=-6.24; 95% CI: -10.36, -2.11) and working memory (adjusted beta=-4.71; 95% CI: -9.05, -0.36) scales at 4years of age. High exposure to PCBs (>=90th percentile) during pregnancy was associated with a 4.62 points reduction in working memory score at 4years of age (95% CI: -9.10, -0.14). Prenatal exposure to DDE, HCB and PCBs was not associated with child behavioral difficulties. CONCLUSIONS: The findings suggest that prenatal exposure to HCB and PCBs may contribute to reduced cognitive development at preschool age. Our results raise the possibility that exposure to HCB may play a more important role in child cognition than previously considered. PMID- 27666325 TI - A hybrid method for quantifying China's nitrogen footprint during urbanisation from 1990 to 2009. AB - In this study, we devise a national nitrogen footprint method to evaluate the life cycle nitrogen flows through the national economy of China from 1990 to 2009. To this end, we build a hybrid method based on two well-established techniques, namely material flow analysis (MFA) and input-output analysis (IOA). This integration allows for the evaluation of the effects of international trade and interdependencies among economic sectors. Our results suggest that China's nitrogen footprint (NF) has increased from 30.3Teragrams (Tg) in 1990 to 54.0Tg in 2009, whereas the NF per capita has increased from 25.9 to 39.5kgN/yr. Relationship between the world NF per capita and human development index (HDI) appears to show an inverted U curve, whilst China shows an increase both in NF per capita and HDI. We find that an increase in China's NF is largely associated with high levels of urbanisation. Although the energy NF (E_NF) has increased more drastically than the food NF (F_NF), the latter still dominates China's total NNF, with proportions of 91% in 1990 and 82% in 2009. Taking international trade into account, our results demonstrate that China was a net exporter of F_NF, whilst a net importer of E_NF over this time period. There are many measures considered to reduce China's nitrogen footprint, including improvements in N use efficiency of food systems, transformation of meat-based diets and optimisation of China's economic structure. PMID- 27666326 TI - Letter to the editor: Digital intraosseous epidermoid inclusion cyst of the distal phalanx. PMID- 27666327 TI - Temporal lobe epilepsy following maintenance electroconvulsive therapy-Electrical kindling in the human brain? AB - Maintenance electroconvulsive therapy (ECT) is sometimes prescribed for refractory psychiatric conditions. We describe five patients who received maintenance ECT and developed florid temporal epileptiform abnormalities on electroencephalography (EEG) despite no history of epilepsy and normal neuroimaging. All patients had received regular ECT for at least 8 months. Three patients had clinical events consistent with epileptic seizures, and video-EEG monitoring captured electrographic seizures in two patients. After cessation of ECT the EEGs normalized in all patients, and no further clinical seizures occurred. Maintenance ECT may predispose to epilepsy with a seizure focus in the temporal lobe. PMID- 27666328 TI - Cutaneous Pseudallescheria boydii/Scedosporium apiospermum complex infection in immunocompromised patients: A report of two cases. PMID- 27666330 TI - Potentially modifiable risk factors for atrial fibrillation following lung resection surgery: a retrospective cohort study. AB - Atrial fibrillation is the most frequent arrhythmia after thoracic surgery and is associated with increased hospital costs, morbidity and mortality. In this study, we aimed to identify potentially modifiable risk factors for postoperative atrial fibrillation following lung resection surgery and to suggest possible measures to reduce risk. We retrospectively reviewed the medical records of 4731 patients who underwent lobectomy or more major lung resection over a 6-year period. Patients who developed atrial fibrillation postoperatively and required treatment were included in the postoperative atrial fibrillation group, while the remaining patients were assigned to the non-postoperative atrial fibrillation group. Risk factors for postoperative atrial fibrillation were analysed by multivariate analysis and propensity score matching. Overall, 12% of patients developed postoperative atrial fibrillation. Potentially modifiable risk factors for postoperative atrial fibrillation were excessive alcohol consumption (odds ratio (OR) = 1.48, 95% CI 1.08-2.02, p = 0.0140), red cell transfusion (2.70(2.13 3.43), p < 0.0001), use of inotropes (1.81(1.42-2.31), p < 0.0001) and open (vs. thoracoscopic) surgery (1.59(1.23-2.05), p < 0.0001). Compared with inotrope use, vasopressor administration was not related to postoperative atrial fibrillation. Use of steroids or thoracic epidural anaesthesia did not reduce the incidence of postoperative atrial fibrillation. We conclude that high alcohol consumption, red cell transfusion, use of inotropes and open surgery are potentially modifiable risk factors for postoperative atrial fibrillation. Pre-operative alcohol consumption needs to be addressed. Avoiding red cell transfusion and performing lung resection via video-assisted thoracoscopic surgery may reduce the incidence of postoperative atrial fibrillation and the administration of vasopressors rather than inotropes is preferred. PMID- 27666329 TI - Pilot study demonstrates that salivary oxytocin can be measured unobtrusively in preterm infants. AB - AIM: This study assessed the feasibility and obtrusiveness of measuring salivary oxytocin in preterm infants receiving Kangaroo care, because this is a period of maximal bonding or co-regulation. We also analysed possible influential determinants, including maternal oxytocin. METHODS: The saliva of preterm infants and their mothers was collected prior to, and during, Kangaroo care using cotton swabs and pooled into vials until sufficient volumes were obtained to measure oxytocin levels using a radioimmunoassay. The obtrusiveness of the infants' collections was measured with a Likert scale. RESULTS: Saliva was collected unobtrusively prior to, and during, 30 Kangaroo care sessions in 21 preterm infants. This resulted in three vials with sufficient volumes of before-Kangaroo care saliva and three with during-Kangaroo care saliva. Oxytocin was detectable in all six vials. The Kangaroo care duration and the intensity of the mother infant interaction before and during Kangaroo care seemed to be the most important determinants, and these should preferably be standardised in any future trials. CONCLUSION: Oxytocin was measured unobtrusively in the pooled saliva of preterm infants both before and during Kangaroo care and could therefore be investigated as a biomarker in future studies. PMID- 27666331 TI - Genetic variation may explain why females are less susceptible to dental erosion. AB - Not all individuals at risk for dental erosion (DE) display erosive lesions. The prevalence of DE is higher among male subjects. The occurrence of DE may depend on more than just acidic challenge, with genetics possibly playing a role. The aim of this study was to investigate the association of enamel-formation genes with DE. One premolar and a saliva sample were collected from 90 individuals. Prepared teeth were immersed in 0.01 M HCl (pH 2.2), and enamel loss (MUm) was measured using white light interferometry. DNA was extracted from saliva, and 15 single-nucleotide polymorphisms were analysed. Allele and genotype frequencies were related to the enamel loss of the specimens. Single-marker and haplotype analyses were performed using sex as a covariate. Mean enamel loss was higher for male donors than for female donors (P = 0.047). Significant associations were found between enamel loss and amelogenin, X-linked (AMELX), tuftelin 1 (TUFT1), and tuftelin-interacting protein 11 (TFIP11). Analyses showed significant associations between variation in enamel-formation genes and a lower susceptibility to DE in female subjects. The results indicate that susceptibility to DE is influenced by genetic variation, and may, in part, explain why some individuals are more susceptible than others to DE, including differences between female subjects and male subjects. PMID- 27666333 TI - Fungal contribution in chondroradionecrosis of the larynx. AB - OBJECTIVE: To assess the prevalence of invasive fungal elements in the specimens of patients who underwent salvage total laryngectomy for chondroradionecrosis (CRN) in the absence of recurrent or persistent malignancy. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. METHODS: One hundred fifty-nine patients were identified who underwent salvage total laryngectomy. Pathology reports were reviewed, and all laryngectomy specimens that did not contain residual malignancy were reevaluated for evidence of invasive fungal elements. RESULTS: Twelve of 159 (7.5%) patients who underwent total laryngectomy after primary radiotherapy or chemoradiotherapy had no evidence of residual malignancy. Each of these specimens contained histopathologic evidence of CRN; invasive fungal elements were identified in 25%. There was no statistical difference in demographic or treatment-related variables between patients who underwent salvage total laryngectomy with evidence of persistent or recurrent malignancy in the laryngectomy specimen versus patients without evidence of tumor on final histopathologic analysis. Patients with evidence of ulceration or necrosis in the laryngectomy specimen had reduced overall survival, irrespective of the presence of persistent malignancy (hazard ratio = 2.923, 95% confidence interval = 1.023-8.352, P = .045). CONCLUSION: Among salvage total laryngectomy patients, no difference was identified between patients who underwent total laryngectomy for recurrent or persistent malignancy after primary radiotherapy and those who received total laryngectomy without evidence of malignancy in their specimens. Invasive fungal elements were detected in several laryngectomy specimens that did not contain residual malignancy. Empiric antifungal therapy may therefore benefit patients diagnosed with CRN who are at risk for progression to nonfunctional larynx. Patients with evidence of ulceration or necrosis in the salvage laryngectomy specimen had worse overall survival. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:E159-E165, 2017. PMID- 27666334 TI - Sarcopenia Screened With SARC-F Questionnaire Is Associated With Quality of Life and 4-Year Mortality. AB - OBJECTIVES: There is no gold standard in diagnosing sarcopenia. We aimed to assess the validity of screening sarcopenia using SARC-F (sluggishness, assistance in walking, rise from a chair, climb stairs, falls). DESIGN: Prospective cohort study. SETTING: Community hospital in Taiwan. PARTICIPANTS: Community-dwelling senior citizens. MEASUREMENTS: Participants were interviewed with a structured questionnaire annually. The questionnaire items were recoded into the 5 items of SARC-F (sluggishness, assistance in walking, rise from a chair, climb stairs, falls). In the baseline year, a subgroup was tested for grip strength and body composition. Healthcare utilization and mortality were based on self-report and hospital records. Our main outcome was 4-year mortality. Secondary outcomes included hospitalization, emergency care use, and quality of life (QOL) measured using the CASP-12 scale (control, autonomy, self-realization, pleasure (control, autonomy, self-realization, pressure). RESULTS: There were 670 participants. The mean age was 76.1 (standard deviation 6.36). One-half were men (n = 340, 50.7%). The prevalence of sarcopenia was 6.1% (n = 41). SARC-F scores were inversely associated with grip strength (P = .001) and skeletal muscle composition (P = .045). Participants with sarcopenia were mostly women (P = .005) and older (P < .001). In univariate analysis, sarcopenia was associated with 1- to 4-year mortalities (P = .033, .001, .001, <.001, respectively), overall hospitalization (P = .004), overall emergency care use (P = .017), and QOL (P < .001). In multivariate model, sarcopenia [odds ratio (OR) 7.35, 95% confidence interval (CI) 2.67-20.18], age (OR 1.19, 95% CI 1.09-1.29 for each year), and taking vitamin D supplements (OR 0.29, 95% CI 0.11-0.74) were factors associated with mortality. CONCLUSIONS: Sarcopenia screened using SARC-F was associated with subsequent QOL, overall hospitalization, overall emergency care use, and 4-year mortality. SARC-F can serve as a quick screening tool of sarcopenia. PMID- 27666332 TI - CCL2 as a potential therapeutic target for clear cell renal cell carcinoma. AB - We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC. PMID- 27666335 TI - The Pursuit of Word Meanings. AB - We evaluate here the performance of four models of cross-situational word learning: two global models, which extract and retain multiple referential alternatives from each word occurrence; and two local models, which extract just a single referent from each occurrence. One of these local models, dubbed Pursuit, uses an associative learning mechanism to estimate word-referent probability but pursues and tests the best referent-meaning at any given time. Pursuit is found to perform as well as global models under many conditions extracted from naturalistic corpora of parent-child interactions, even though the model maintains far less information than global models. Moreover, Pursuit is found to best capture human experimental findings from several relevant cross situational word-learning experiments, including those of Yu and Smith (), the paradigm example of a finding believed to support fully global cross-situational models. Implications and limitations of these results are discussed, most notably that the model characterizes only the earliest stages of word learning, when reliance on the co-occurring referent world is at its greatest. PMID- 27666336 TI - Down-regulation of hepatic CYP3A1 expression in a rat model of indomethacin induced small intestinal ulcers. AB - The liver and the small intestine are closely related in the processes of drug absorption, metabolism and excretion via the enterohepatic circulation. Small intestinal ulcers are a serious adverse effect commonly occurring in patients taking nonsteroidal anti-inflammatory drugs. However, the influence of small intestinal ulcers on drug metabolism has not been established. This study examined the expressional changes of cytochrome P450 (CYP) in the liver using an indomethacin-induced small intestinal ulcer rat model and in cultured cells. After the administration of indomethacin to rats, ulcers were observed in the small intestine and expression of CYP3A1, the major isoform of hepatic CYP, was significantly down-regulated in the liver, accompanied by increased expression of inducible nitric oxide synthase, tumor necrosis factor alpha, interleukin (IL) 1beta and IL-6, in the small intestine and the liver. The indomethacin-induced small intestinal ulceration, the increase in inflammatory mediators in the small intestine and the liver, and the down-regulation of CYP3A1 expression in the liver were inhibited by co-administration of ampicillin, an antibacterial agent. In the human hepatic HepG2 cell line, IL-1beta, IL-6 and NOC-18, an NO donor, caused down-regulation of CYP3A4, the major isoform of human CYP3A. Thus, this study suggests that after indomethacin treatment small intestinal ulcers cause the down-regulation of CYP3A1 in the rat liver through an increase in ulcer derived inflammatory mediators. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27666337 TI - The septins FaCdc3 and FaCdc12 are required for cytokinesis and affect asexual and sexual development, lipid metabolism and virulence in Fusarium asiaticum. AB - Septins are a highly conserved family of GTP-binding proteins that contribute to many cellular and metabolic functions, including cell polarity, cytokinesis, cell morphogenesis and pathogenesis. In this study, we characterized the septins FaCdc3 and FaCdc12 in the filamentous fungus Fusarium asiaticum. The functions of FaCdc3 and FaCdc12 were evaluated by constructing deletion mutants of FaCdc3 and FaCdc12, designated DeltaFaCdc3-5 and DeltaFaCdc12-71, respectively. The deletion mutants exhibited a reduced rate of mycelial growth, increased aerial hyphae formation, irregularly shaped hyphae, reduced conidiation and a lack of sexual reproduction in wheat kernels. Histochemical analysis revealed that the conidia and hyphae of DeltaFaCdc3-5 and DeltaFaCdc12-71 formed large lipid droplets (LDs). DeltaFaCdc3-5 and DeltaFaCdc12-71 also exhibited increased resistance to agents that induce osmotic stress and damage the cell membrane and cell wall. In addition, the hyphae and conidia of the two mutants formed fewer septa than those of the wild-type and exhibited aberrant nuclear distribution. Pathogenicity assays showed that DeltaFaCdc3-5 and DeltaFaCdc12-71 exhibited reduced virulence on wheat spikelets, which was indirectly correlated with a reduced level of deoxynivalenol accumulation. All of these defects were restored by genetic complementation of the two mutants with the parental FaCdc3 and FaCdc12. These results indicate that FaCdc3 and FaCdc12 play a critical role in various cellular processes in F. asiaticum. PMID- 27666339 TI - The change in the sex ratio in multiple sclerosis is driven by birth cohort effects. AB - BACKGROUND AND PURPOSE: Birth cohort effects have greatly shaped long-term trends in multiple sclerosis (MS). This study examined whether birth cohort effects have also determined trends in the sex ratio. METHODS: Age-period-cohort analyses were applied to Swiss mortality data, 1901-2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C. RESULTS: Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex-specific birth cohort estimates were not congruent. CONCLUSION: The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex-specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors. PMID- 27666338 TI - Exploring uses of the UK Clinical Aptitude Test-situational judgement test in a dental student selection process. AB - AIM: In 2013 the UKCAT included a non-cognitive situational judgement test in addition to the four cognitive subtests commonly used by UK dental schools to select students. However, little is known about the situational judgement test's psychometric properties and relationship to other selection tools. This study's aim was explore these issues to inform decisions about the inclusion of the UKCAT SJT in the dental student selection process. METHOD: The sample comprised a cohort of applicants to a Bachelor of Dental Surgery programme, at a UK dental school, which does not use achievement in the UKCAT SJT in its selection process. The impact on applicant outcomes of two theoretical uses of the UKCAT SJT was examined. First, SJT Band was used as the criterion for offers of a place instead of the school's admission interview, and second, weighted UKCAT scores, including a weighted SJT Band score, were ranked to make interview invitation decisions. Associations between SJT Band, UKCAT cognitive scores, interview score and performance in first year assessments were examined. RESULTS: If SJT Band 1 & 2 were used as the criterion for an offer of a place, some applicants rejected by this school's interview, including 'red flagged' applicants, would have received an offer of a place. Using a weighted UKCAT/SJT system for invitation for interview decisions increased the mean total UKCAT cognitive score of those invited for interview but included applicants rejected by this school's structured interview, including 'red flagged' applicants. Neither usage disadvantaged under-represented groups. SJT Band correlated with UKCAT score (n = 228, rs = -0.38, P < 0.01) with interview score (n = 186, rs = -0.17, P < 0.05) but not with first year study assessments. CONCLUSION: This study has shown that the UKCAT SJT does not add value to the existing methods of this dental school to make valid, reliable and fair student selection decisions. PMID- 27666340 TI - [Because it is possible to heal...!]. PMID- 27666341 TI - Surgical management of parotid salivary duct rupture secondary to non-iatrogenic trauma in a dog. AB - A 3-year-old French bulldog presented for evaluation of recurrent swelling and a fistula on the right cheek after a dog fight. A large volume of serous fluids was identified on the wound immediately after atropine drops. A diagnosis of parotid salivary duct rupture secondary to trauma was made. On surgical exploration, the thickened proximal segment of the severed duct was identified and circumferentially double ligated with 3-0 silk. No evidence of swelling and normal appearance of the parotid salivary gland were identified 4 months postoperative recheck. No further problems were noted 10 months postoperatively phone-call. To the author's knowledge, this is the first reported case of successful proximal parotid duct ligation of parotid salivary duct rupture secondary to non-iatrogenic trauma. PMID- 27666342 TI - Tympanoplasty for chondrodysplasia punctata: Case report. AB - Chondrodysplasia punctata (CP) is a systemic disorder of chondrogenesis. The most prominent features of patients with CP are abnormal faces characterized by a flat nose and short stature. CP patients show various types and levels of hearing loss. This disease is rare, and no successful tympanoplasties with hearing recovery have been reported. Here, we report on a CP case, in which hearing recovery was successfully treated with tympanoplasty. PMID- 27666344 TI - Corrigendum to "The-effect-of-triiodothyronine-on-maturation-and-differentiation of-oligodendrocyte-progenitor-cells-during-remyelination-following-induced demyelination in male albino rat" [Tissue Cell 48 (March (3)) (2016) 242-251]. PMID- 27666343 TI - Combination of Palonosetron, Aprepitant, and Dexamethasone Effectively Controls Chemotherapy-induced Nausea and Vomiting in Patients Treated with Concomitant Temozolomide and Radiotherapy: Results of a Prospective Study. AB - Concomitant use of temozolomide (TMZ) and radiotherapy, which is the standard therapy for patients with high-grade glioma, involves a unique regimen with multiple-day, long-term administration. In a previous study, we showed not only higher incidence rates of chemotherapy-induced nausea and vomiting (CINV) during the overall study period, but also substantially higher incidence rates of moderate/severe nausea and particularly severe appetite suppression during the late phase of the treatment. Here, we prospectively evaluated the efficacy of a combination of palonosetron, aprepitant, and dexamethasone for CINV in patients treated with concomitant TMZ and radiotherapy. Twenty-one consecutive patients with newly diagnosed high-grade glioma were enrolled. CINV was recorded using a daily diary and included nausea assessment, emetic episodes, degree of appetite suppression, and use of antiemetic medication. The percentage of patients with a complete response in the overall period was 76.2%. The percentages of patients with no moderate/severe nausea were 90.5, 100, and 90.5% in the early phase, late phase, and overall period, respectively. Severe appetite suppression throughout the overall period completely disappeared. The combination of palonosetron, aprepitant, and dexamethasone was highly effective and well tolerated in patients treated with concomitant TMZ and radiotherapy. This combination of antiemetic therapy focused on delayed as well as acute CINV and may have the potential to overcome CINV associated with a multiple-day, long-term chemotherapy regimen. PMID- 27666345 TI - Identification and characterization of multiple emissive species in aggregated minor antenna complexes. AB - Aggregation induced conformational change of light harvesting antenna complexes is believed to constitute one of the pathways through which photosynthetic organisms can safely dissipate the surplus of energy while exposed to saturating light. In this study, Stark fluorescence (SF) spectroscopy is applied to minor antenna complexes (CP24, CP26 and CP29) both in their light-harvesting and energy dissipating states to trace and characterize different species generated upon energy dissipation through aggregation (in-vitro) induced conformational change. SF spectroscopy could identify three spectral species in the dissipative state of CP24, two in CP26 and only one in CP29. The comprehensive analysis of the SF spectra yielded different sets of molecular parameters for the multiple spectral species identified in CP24 or CP26, indicating the involvement of different pigments in their formation. Interestingly, a species giving emission around the 730nm spectral region is found to form in both CP24 and CP26 following transition to the energy dissipative state, but not in CP29. The SF analyses revealed that the far red species has exceptionally large charge transfer (CT) character in the excited state. Moreover, the far red species was found to be formed invariably in both Zeaxanthin (Z)- and Violaxathin (V)-enriched CP24 and CP26 antennas with identical CT character but with larger emission yield in Z-enriched ones. This suggests that the carotenoid Z is not directly involved but only confers an allosteric effect on the formation of the far red species. Similar far red species with remarkably large CT character were also observed in the dissipative state of the major light harvesting antenna (LHCII) of plants [Wahadoszamen et al. PCCP, 2012], the fucoxanthin-chlorophyll protein (FCP) of brown algae [Wahadoszamen et al. BBA, 2014] and cyanobacterial IsiA [Wahadoszamen et al. BBA, 2015], thus pointing to identical sites and pigments active in the formation of the far red quenching species in different organisms. PMID- 27666347 TI - A Sobering Look at the Financial Reality for New Physicians: It's Time to Advocate for Change. PMID- 27666348 TI - Male With Shortness of Breath. PMID- 27666346 TI - FRMD4A: A potential therapeutic target for the treatment of tongue squamous cell carcinoma. AB - The aim of the present study was to identify agents capable of inhibiting the invasion and metastasis of tongue squamous cell carcinoma and thereby improve the outcomes of patients suffering from tongue cancer. FRMD4A antibodies were used to probe 78 paraffin-embedded specimens of tongue squamous cell carcinoma and 15 normal tongue tissues, which served as controls. Immunohistochemical methods were then used for analysis. Clinical pathological parameters were obtained, and the association between FRMD4A expression in the samples and the pathological parameters was analyzed. The human tongue cancer cell line CAL27 was used to study the effects of FRMD4A. CAL27 cells were transfected with small-interfering RNA against FRMD4A (FRMD4A-siRNA) and the mRNA and protein levels of FMRD4A were then evaluated by RT-qPCR and western blot analysis, respectively. The proliferation and cell-cycle assays of CAL27 cells were evaluated using the CCK8 method and flow cytometry. The invasion and migration of the cells were measured using a Matrigel invasion chamber and a scratch assay, respectively. The results showed FRMD4A overexpression in tongue squamous cell carcinoma, and the positive reaction was predominately located in the cytoplasm. Tumor clinical stage and lymph node metastasis showed a statistically significant correlation with FRMD4A expression. Transient silencing of the FRMD4A gene for 24 and 48 h significantly decreased the mRNA and protein expression of FRMD4A, respctively. Silencing FRMD4A gene reduced the proliferation of CAL27 cells and led to cell cycle arrest in the G1 phase, as well as significantly suppressing the migration and invasion capacity of CAL27 cells. The findings of the present study suggest that FRMD4A expression correlates with the development of tongue squamous cell carcinoma. For this reason, FRMD4A merits further study as it may be suitable for use as a therapeutic agent in antitumor treatment regimens. PMID- 27666350 TI - Empowerment. PMID- 27666349 TI - Woman With Pain in Left Leg. PMID- 27666351 TI - across my oval mirror. PMID- 27666352 TI - Rating the Ratings: The AIR Scoring System for Blogs and Podcasts: Answers to the May 2016 Annals Journal Club Questions. PMID- 27666353 TI - Boy With Upper Neck Pain and Generalized Weakness. PMID- 27666354 TI - Elderly Man With Abdominal Rash. PMID- 27666355 TI - A Sample Rule-Out Tuberculosis Protocol. PMID- 27666356 TI - Was the Effect of Antibiotic Administration Time Adjusted Properly? PMID- 27666357 TI - In reply. PMID- 27666358 TI - Snapchat Toxicology: Social Media and Suicide. PMID- 27666359 TI - Drug "Take-Back" Programs. PMID- 27666360 TI - Male With Numbness and Muscle Spasms. PMID- 27666361 TI - Elderly Woman With Severe Abdominal Pain. PMID- 27666362 TI - Man With Abdominal Wall Abscess. PMID- 27666363 TI - Male With Diabetes and a Rash. PMID- 27666364 TI - Female With Fever. PMID- 27666365 TI - RUNX2 promotes hepatocellular carcinoma cell migration and invasion by upregulating MMP9 expression. AB - Runt-related transcription factor 2 (RUNX2) was first identified as a transcription factor to play an important role in different biological processes of osteoblast and chondrocyte, including differentiation and migration. Recently, RUNX2 has been implicated in promigratory/proinvasive behavior in different human malignancies. In the present study, we demonstrated that the RUNX2 mRNA and protein expression were both increased significantly in HCC tissues and cell lines. High RUNX2 expression was correlated obviously with poor clinicopathological characteristics including multiple tumor nodes, high histological grading, venous infiltration and advanced tumor-node-metastasis (TNM) stage. In addition, we demonstrated that RUNX2 was a prognostic indicator for predicting 5-year overall survival and disease-free survival of HCC patients. Our studies showed that RUXN2 overexpression promoted, while RUNX2 knockdown inhibited HCC cell migration and invasion in vitro. Notably, RUNX2 positively regulated matrix metalloproteinase 9 (MMP9) accumulation in HCC cells. Furthermore, we confirmed that RUNX2 was positively correlated with MMP9 expression in HCC tissues by Pearson correlation analysis. Mechanistically, we demonstrated that MMP9 overexpression increased HCC cell migration and invasion, while MMP9 knockdown reduced HCC cell migration and invasion in vitro. Alteration of MMP9 expression partially abrogated the effects of RUNX2 on HCC cell migration and invasion, which suggests that RUNX2 developed its pro-metastatic biological function by upregulating the expression of MMP9 in HCC cells. In conclusion, our results reveal that RUNX2 promotes HCC cell migration and invasion by MMP9 mediated pathway, and potentially serves as a new prognostic biomarker and in therapeutic strategies for HCC. PMID- 27666366 TI - PEDOT:PSS organic electrochemical transistor arrays for extracellular electrophysiological sensing of cardiac cells. AB - Electrophysiological biosensors embedded in planar devices represent a state of the art approach to measure and evaluate the electrical activity of biological systems. This measurement method allows for the testing of drugs and their influences on cells or tissues, cytotoxicity, as well as the direct implementation into biological systems in vivo for signal transduction. Multi electrode arrays (MEAs) with metal or metal-like electrodes on glass substrates are one of the most common, well-established platforms for this purpose. In recent years organic electrochemical transistors (OECTs) made of poly(2,3 dihydrothieno-1,4-dioxin)-poly(styrenesulfonate) (PEDOT:PSS) have as well shown their value in transducing and amplifying the ionic signals in biological systems. We developed OECT devices in a wafer-scale process and used them as electrophysiological biosensors measuring electrophysiological activity of the cardiac cell line HL-1. Our optimized devices show very promising properties such as good signal-to-noise ratio as well as the ability to record fast components of extracellular signals. Combined with an easy, cost effective fabrication and the transparency of the polymer, this platform offers a valuable alternative to traditional MEA systems for future cell sensing applications. PMID- 27666367 TI - Development of an electrochemical detection system for measuring DNA methylation levels using methyl CpG-binding protein and glucose dehydrogenase-fused zinc finger protein. AB - DNA methylation level at a certain gene region is considered as a new type of biomarker for diagnosis and its miniaturized and rapid detection system is required for diagnosis. Here we have developed a simple electrochemical detection system for DNA methylation using methyl CpG-binding domain (MBD) and a glucose dehydrogenase (GDH)-fused zinc finger protein. This analytical system consists of three steps: (1) methylated DNA collection by MBD, (2) PCR amplification of a target genomic region among collected methylated DNA, and (3) electrochemical detection of the PCR products using a GDH-fused zinc finger protein. With this system, we have successfully measured the methylation levels at the promoter region of the androgen receptor gene in 106 copies of genomic DNA extracted from PC3 and TSU-PR1 cancer cell lines. Since no sequence analysis or enzymatic digestion is required for this detection system, DNA methylation levels can be measured within 3h with a simple procedure. PMID- 27666368 TI - Effects of expectation congruency on event-related potentials (ERPs) to facial expressions depend on cognitive load during the expectation phase. AB - Previous studies have shown that event-related potentials (ERPs) to facial expressions are modulated by expectation (congruency) and that the ERP effects of expectation congruency are altered by cognitive tasks during the expectation phase. However, it is as yet unknown whether the congruency ERP effects can be modulated by the amount of cognitive load during the expectation phase. To address this question, electroencephalogram (EEG) was acquired when participants viewed fearful and neutral facial expressions. Before the presentation of facial expressions, a cue indicating the expression of a face and subsequently, an expectation interval without any cues were presented. Facial expressions were congruent with the cues in 75% of all trials. During the expectation interval, participants had to solve a cognitive task, in which several letters were presented for target letter detection. The letters were all the same under low load, but differed under high load. Event-related potential (ERP) results showed that the amount of cognitive load during the expectation phase altered the congruency effect in N2 and EPN amplitudes for fearful faces. Congruent as compared to incongruent fearful expressions elicited larger N2 and smaller EPN amplitudes under low load, but these congruency effects were not observed under high load. For neutral faces, a congruency effect in late positive potential (LPP) amplitudes was modulated by cognitive load during the expectation phase. The LPP was more positive for incongruent as compared to congruent faces under low load, but the congruency effect was not evident under high load. The findings indicate that congruency effects on ERPs are modulated by the amount of cognitive load the expectation phase and that this modulation is altered by facial expression. PMID- 27666369 TI - TBCE Mutations Cause Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy. AB - Tubulinopathies constitute a family of neurodevelopmental/neurodegenerative disorders caused by mutations in several genes encoding tubulin isoforms. Loss-of function mutations in TBCE, encoding one of the five tubulin-specific chaperones involved in tubulin folding and polymerization, cause two rare neurodevelopmental syndromes, hypoparathyroidism-retardation-dysmorphism and Kenny-Caffey syndrome. Although a missense mutation in Tbce has been associated with progressive distal motor neuronopathy in the pmn/pmn mice, no similar degenerative phenotype has been recognized in humans. We report on the identification of an early-onset and progressive neurodegenerative encephalopathy with distal spinal muscular atrophy resembling the phenotype of pmn/pmn mice and caused by biallelic TBCE mutations, with the c.464T>A (p.Ile155Asn) change occurring at the heterozygous/homozygous state in six affected subjects from four unrelated families originated from the same geographical area in Southern Italy. Western blot analysis of patient fibroblasts documented a reduced amount of TBCE, suggestive of rapid degradation of the mutant protein, similarly to what was observed in pmn/pmn fibroblasts. The impact of TBCE mutations on microtubule polymerization was determined using biochemical fractionation and analyzing the nucleation and growth of microtubules at the centrosome and extracentrosomal sites after treatment with nocodazole. Primary fibroblasts obtained from affected subjects displayed a reduced level of polymerized alpha-tubulin, similarly to tail fibroblasts of pmn/pmn mice. Moreover, markedly delayed microtubule re-polymerization and abnormal mitotic spindles with disorganized microtubule arrangement were also documented. Although loss of function of TBCE has been documented to impact multiple developmental processes, the present findings provide evidence that hypomorphic TBCE mutations primarily drive neurodegeneration. PMID- 27666371 TI - Increasing Generality and Power of Rare-Variant Tests by Utilizing Extended Pedigrees. AB - Recently, multiple studies have performed whole-exome or whole-genome sequencing to identify groups of rare variants associated with complex traits and diseases. They have primarily utilized case-control study designs that often require thousands of individuals to reach acceptable statistical power. Family-based studies can be more powerful because a rare variant can be enriched in an extended pedigree and segregate with the phenotype. Although many methods have been proposed for using family data to discover rare variants involved in a disease, a majority of them focus on a specific pedigree structure and are designed to analyze either binary or continuously measured outcomes. In this article, we propose RareIBD, a general and powerful approach to identifying rare variants involved in disease susceptibility. Our method can be applied to large extended families of arbitrary structure, including pedigrees with only affected individuals. The method accommodates both binary and quantitative traits. A series of simulation experiments suggest that RareIBD is a powerful test that outperforms existing approaches. In addition, our method accounts for individuals in top generations, which are not usually genotyped in extended families. In contrast to available statistical tests, RareIBD generates accurate p values even when genetic data from these individuals are missing. We applied RareIBD, as well as other methods, to two extended family datasets generated by different genotyping technologies and representing different ethnicities. The analysis of real data confirmed that RareIBD is the only method that properly controls type I error. PMID- 27666370 TI - Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy. AB - Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the alphabeta-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective beta-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble alpha/beta-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with impact on neuronal function and survival in the developing brain. PMID- 27666372 TI - Guidelines for Large-Scale Sequence-Based Complex Trait Association Studies: Lessons Learned from the NHLBI Exome Sequencing Project. AB - Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS. PMID- 27666373 TI - REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. AB - The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10-12) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies <0.5%. The area under the receiver operating characteristic curve (AUC) for REVEL was 0.046-0.182 higher in an independent test set of 935 recent SwissVar disease variants and 123,935 putatively neutral exome sequencing variants and 0.027-0.143 higher in an independent test set of 1,953 pathogenic and 2,406 benign variants recently reported in ClinVar than the AUCs for other ensemble methods. We provide pre computed REVEL scores for all possible human missense variants to facilitate the identification of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in scale. PMID- 27666375 TI - Predicting the Crystallization Propensity of Drug-Like Molecules. AB - Predicting the crystallization propensity of drug-like molecules is one of the most significant challenges facing pharmaceutical scientists today. Despite the importance of being able to understand what structural features of a molecule (polarity, molecular size, etc.) and which experimental conditions (temperature, concentration, etc.) permit a molecule to crystallize, there has been very little published work focused on this topic. This commentary provides a short overview of recent progress in this area and points to potential experimental and computational approaches that might be used in the future. PMID- 27666376 TI - Freeze-Drying Process Development and Scale-Up: Scale-Up of Edge Vial Versus Center Vial Heat Transfer Coefficients, Kv. AB - This report presents calculations of the difference between the vial heat transfer coefficient of the "edge vial" and the "center vial" at all scales. The only scale-up adjustment for center vials is for the contribution of radiation from the shelf upon which the vial sits by replacing the emissivity of the laboratory dryer shelf with the emissivity of the production dryer shelf. With edge vials, scales-up adjustments are more complex. While convection is not important, heat transfer from the wall to the bands (surrounding the vial array) by radiation and directly from the band to the vials by both radiation and conduction is important; this radiation heat transfer depends on the emissivity of the vial and the bands and is nearly independent of the emissivity of the dryer walls. Differences in wall temperatures do impact the edge vial effect and scale-up, and estimates for wall temperatures are needed for both laboratory and manufacturing dryers. Auto-loading systems (no bands) may give different edge vial heat transfer coefficients than when operating with bands. Satisfactory agreement between theoretical predictions and experimental values of the edge vial effect indicate that results calculated from the theory are of useful accuracy. PMID- 27666374 TI - Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy. AB - We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and beta-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. PMID- 27666377 TI - Application of Artificial Neural Networks in the Design and Optimization of a Nanoparticulate Fingolimod Delivery System Based on Biodegradable Poly(3 Hydroxybutyrate-Co-3-Hydroxyvalerate). AB - Formulation of a nanoparticulate Fingolimod delivery system based on biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) was optimized according to artificial neural networks (ANNs). Concentration of poly(3 hydroxybutyrate-co-3-hydroxyvalerate), PVA and amount of Fingolimod is considered as the input value, and the particle size, polydispersity index, loading capacity, and entrapment efficacy as output data in experimental design study. In vitro release study was carried out for best formulation according to statistical analysis. ANNs are employed to generate the best model to determine the relationships between various values. In order to specify the model with the best accuracy and proficiency for the in vitro release, a multilayer percepteron with different training algorithm has been examined. Three training model formulations including Levenberg-Marquardt (LM), gradient descent, and Bayesian regularization were employed for training the ANN models. It is demonstrated that the predictive ability of each training algorithm is in the order of LM > gradient descent > Bayesian regularization. Also, optimum formulation was achieved by LM training function with 15 hidden layers and 20 neurons. The transfer function of the hidden layer for this formulation and the output layer were tansig and purlin, respectively. Also, the optimization process was developed by minimizing the error among the predicted and observed values of training algorithm (about 0.0341). PMID- 27666379 TI - Evaluating Clinical Nutrition Managers' Involvement in Key Management Functions. PMID- 27666378 TI - What's Being Served for Dinner? An Exploratory Investigation of the Associations between the Healthfulness of Family Meals and Child Dietary Intake. AB - BACKGROUND: Little is known about the healthfulness of foods offered at family meals or the relationship between the food's healthfulness and child overall dietary intake. OBJECTIVE: This exploratory study uses a newly developed Healthfulness of Meal Index to examine the association between the healthfulness of foods served at family dinners and child dietary intake. DESIGN: Direct observational, cross-sectional study. PARTICIPANTS/SETTING: Primarily low-income, minority families (n=120) video recorded 8 days of family dinners and completed a corresponding meal screener. Dietary recalls were completed on the target child (6 to 12 years old). The Healthfulness of Meal Index was used to measure meal healthfulness and included component scores for whole fruit, 100% juice, vegetables, dark green vegetables, dairy, protein, added sugars, and high-sodium foods. MAIN OUTCOME MEASURES: Child dietary intake measured by three 24-hour dietary recalls. STATISTICAL ANALYSES PERFORMED: Linear regression models estimated the association between the healthfulness of foods served at dinner meals and overall child HEI. RESULTS: The majority of coded meals included foods from protein and high-sodium components; more than half included foods from dairy and vegetable components. Nearly half of the meals had an added-sugar component food (eg, soda or dessert). Few meals served foods from fruit, 100% juice, or dark green vegetable components. Many components served at family dinner meals were significantly associated with child daily intake of those same foods (ie, dark green vegetable, non-dark green vegetables, dairy, and added sugars). The Healthfulness of Meal Index total score was significantly associated with child HEI score. CONCLUSIONS: This study represents the first report of a new methodology to collect data of foods served at family dinners. Results indicated a significant association between the majority of components served at family dinner meals and child overall dietary intake. Validation of the Healthfulness of Meal Index and video-recorded family meal methodology is needed to strengthen these research methods for use in future studies. PMID- 27666381 TI - Acute alcohol exposure increases tyrosine hydroxylase protein expression and dopamine synthesis in zebrafish. AB - Zebrafish have become a popular animal model for investigating the effects of alcohol on the brain and behaviour. Acute exposure to alcohol has been shown to alter dopaminergic signalling in zebrafish, but the underlying mechanisms have not been well defined. In the current study, we characterize the effects of alcohol on the zebrafish dopaminergic system by focusing on tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Using western blot analysis, we demonstrate that a 60min exposure to 1% alcohol increases tyrosine hydroxylase protein expression in the zebrafish brain. Enzymatic activity assays confirmed that alcohol also increases tyrosine hydroxylase enzymatic activity, whereas HPLC analysis demonstrated increased levels of whole-brain dopamine and its metabolite DOPAC. In addition to activation of the dopaminergic system, behavioural analysis revealed accompanying increase of distance traveled following 1% alcohol exposure. These findings suggest that acute alcohol exposure elevates dopamine synthesis via increased tyrosine hydroxylase protein expression. Our results support the hypothesis that alcohol alters dopaminergic signalling in the zebrafish brain in a similar manner as compared to mammals. PMID- 27666380 TI - Associations between Dietary Patterns and Blood Pressure in a Clinical Sample of Overweight Adults. AB - BACKGROUND: Dietary pattern analysis provides important evidence revealing diet disease relationships. It may be especially useful in areas less well researched, such as diet and hypertension in clinical populations. OBJECTIVE: The aim of this study was to identify the association between dietary patterns and blood pressure (BP) in a sample of overweight adults volunteering for a clinical trial for weight loss. DESIGN: This cross-sectional analysis used baseline data from the HealthTrack study, a 12-month randomized controlled trial. Dietary intake was evaluated with 4-day food records. PARTICIPANTS/SETTING: Participants were 328 adults recruited from the Illawarra region of New South Wales, Australia, between May 2014 and April 2015. MAIN OUTCOME MEASURES: Resting BP and 24-hour urine sodium and potassium were measured. STATISTICAL ANALYSIS: Dietary patterns were derived by principal component analysis from 21 food groups. Multiple regression analysis was performed to assess the association between the extracted dietary patterns and BP. RESULTS: The participants' mean age was 43.6+/-8.0 years, mean body mass index was 32.4+/-4.2, and mean systolic BP/diastolic BP was 124.9+/ 14.5/73.3+/-9.9 mm Hg. Six major dietary patterns were identified: "nuts, seeds, fruit, and fish," "milk and meat," "breads, cereals, and snacks," "cereal-based products, fats, and oils," "alcohol, eggs, and legumes," and "savoury sauces, condiments, and meat." The "nuts, seeds, fruit, and fish" dietary pattern was significantly and inversely associated with systolic BP (F [7,320]=15.248; P<0.0005; adjusted R2=0.234 and diastolic BP (F [7,320]=17.351; P<0.0005; adjusted R2=0.259) and sodium-to-potassium ratio (F [7,320]=6.210; P<0.0005; adjusted R2=0.100). CONCLUSIONS: A dietary pattern rich in nuts, seeds, fruit, and fish was inversely associated with blood pressure in this clinical sample. The findings suggest that current dietary guidelines are relevant to an overweight clinical population and support the value of dietary pattern analysis when exploring the diet-disease relationship. PMID- 27666382 TI - Suboptimal maternal diets alter mu opioid receptor and dopamine type 1 receptor binding but exert no effect on dopamine transporters in the offspring brain. AB - Birthweight is a marker for suboptimal fetal growth and development in utero. Offspring can be born large for gestational age (LGA), which is linked to maternal obesity or excessive gestational weight gain, as well as small for gestational age (SGA), arising from nutrient or calorie deficiency, placental dysfunction, or other maternal conditions (hypertension, infection). In humans, LGA and SGA babies are at an increased risk for certain neurodevelopmental disorders, including Attention Deficit/Hyperactivity Disorder, schizophrenia, and social and mood disorders. Using mouse models of LGA (maternal high fat (HF) diet) and SGA (maternal low protein (LP) diet) offspring, our lab has previously shown that these offspring display alterations in the expression of mesocorticolimbic genes that regulate dopamine and opioid function, thus indicating that these brain regions and neurotransmitter systems are vulnerable to gestational insults. Interestingly, these two maternal diets affected dopamine and opioid systems in somewhat opposing directions (e.g., LP offspring are generally hyperdopaminergic with reduced opioid expression, and the reverse is found for the HF offspring). These data largely involved evaluation at the transcriptional level, so the present experiment was designed to extend these analyses through an assessment of receptor binding. In this study, control, SGA and LGA offspring were generated from dams fed control, low protein or high fat diet, respectively, throughout pregnancy and lactation. At weaning, mice were placed on the control diet and sacrificed at 12 weeks of age. In vitro autoradiography was used to measure mu-opioid receptor (MOR), dopamine type 1 receptor (D1R), and dopamine transporter (DAT) binding level in mesolimbic brain regions. Results showed that the LP offspring (males and females) had significantly higher MOR and D1R binding than the control animals in the regions associated with reward. In HF offspring there were no differences in MOR binding, and limited increases in D1R binding, seen only in females in the nucleus accumbens core and the dorsomedial caudate/putamen. DAT binding revealed no differences in either models. In conclusion, LP but not HF offspring show significantly elevated MOR and D1R binding in the brain thus affecting DA and opioid signaling. These findings advance the current understanding of how suboptimal gestational diets can adversely impact neurodevelopment and increase the risk for disorders such as ADHD, obesity and addiction. PMID- 27666383 TI - Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice. AB - BACKGROUND: Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count. METHODS: We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression. RESULTS: AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers. CONCLUSIONS: AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model. PMID- 27666384 TI - Cognitive control in the eye of the beholder: Electrocortical theta and alpha modulation during response preparation in a cued saccade task. AB - The oscillatory dynamics of medial frontal EEG theta and posterior alpha are implicated in the modulation of attention and cognitive control. We used a novel saccade cueing paradigm to examine whether theta and alpha are modulated by task difficulty during response preparation. After isolating and functionally classifying medial frontal and posterior alpha independent components, the EEG spectral power in these components was calculated on pro- and anti-saccade trials prior to response probes. The results of bootstrap re-sampling show that, compared to pro-saccade trials, correct anti-saccades are characterized by an increase in medial frontal theta and suppression of posterior alpha during the response preparation period. Furthermore, an absence of increased medial frontal theta prior to anti-saccades probes occurs on error trials, that is, a failure to control pre-potent eye movements. For these error trials, a burst in medial frontal theta is instead observed following error feedback. Our findings show that enhanced medial frontal theta is linked not only to dynamic cognitive control that is reactive (such as, after error commission), but is also an important prerequisite for success when behavioral control is challenged. PMID- 27666386 TI - Consistency-based thresholding of the human connectome. AB - Densely seeded probabilistic tractography yields weighted networks that are nearly fully connected, hence containing many spurious fibers. It is thus necessary to prune spurious connections from probabilistically-derived networks to obtain a more reliable overall estimate of the connectivity. A standard method is to threshold by weight, keeping only the strongest edges. Here, by measuring the consistency of edge weights across subjects, we propose a new thresholding method that aims to reduce the rate of false-positives in group-averaged connectivity matrices. Close inspection of the relationship between consistency, weight, and distance suggests that the most consistent edges are in fact those that are strong for their length, rather than simply strong overall. Hence retaining the most consistent edges preserves more long-distance connections than traditional weight-based thresholding, which penalizes long connections for being weak regardless of anatomy. By comparing our thresholded networks to mouse and macaque tracer data, we also show that consistency-based thresholding exhibits the species-invariant exponential decay of connection weights with distance, while weight-based thresholding does not. We also show that consistency-based thresholding can be used to identify highly consistent and highly inconsistent subnetworks across subjects, enabling more nuanced analyses of group-level connectivity than just the mean connectivity. PMID- 27666387 TI - Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen). AB - Four novel compounds (1-4) as well as fourteen reported compounds (5-18) were isolated and purified from Salvia miltiorrhiza Bunge (Danshen). The structures of novel compounds were determined by 1D and 2D NMR, HRESIMS data, etc. The anti inflammatory properties of all the compounds on RAW264.7 macrophages and their cytotoxicity on H1299 and Bel-7402 cell lines coupled with a structure-activity relationship (SAR) were investigated. Compound 4 demonstrated the best anti inflammatory activity and was chosen for further research. Compound 4 greatly suppressed secretion of nitric oxide (NO), tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) in the RAW264.7 macrophages stimulated by LPS. Additionally, the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased and the nuclear translocation of NF-kappaB was attenuated after treatment with compound 4 in vitro. Compound 4 was able to dramatically inhibit LPS-induced activation of JNK1/2 and ERK1/2 and remarkably disrupted the TLR4 dimerization in LPS-induced RAW264.7 macrophages. Thus, the new compound 4 suppressed LPS-induced inflammation partially is due to the blocking TLR4 dimerization. In addition, the anti-cancer activity investigation indicated that most of isolated compounds exhibited cytotoxicity and the SAR analysis showed that the intact D ring was indispensable and unsaturated D ring played vital role. PMID- 27666388 TI - Transcriptional profile of SH-SY5Y human neuroblastoma cells transfected by Toxoplasma rhoptry protein 16. AB - Toxoplasma rhoptry protein 16 (ROP16) is crucial in the host-pathogen interaction by acting as a virulent factor during invasion. To improve understanding of the molecular function underlying the effect of ROP16 on host cells, the present study analyzed the transcriptional profile of genes in the ROP16-transfected SH SY5Y human neuroblastoma cell line. The transcriptional profile of the SH-SY5Y human neuroblastoma cell line overexpressing ROP16 were determined by microarray analysis in order to determine the host neural cell response to the virulent factor. Functional analysis was performed using the Protein Analysis Through Evolutionary Relationships classification system. The ToppGene Suite was used to select candidate genes from the differentially expressed genes. A protein-protein interaction network was constructed using Cytoscape software according to the interaction associations determined using the Search Tool for the Retrieval of Interacting Genes/Proteins. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis of the selected genes confirmed the results of the microarray. The results showed that 383 genes were differentially expressed in response to ROP16 transfection, of which 138 genes were upregulated and 245 genes were downregulated. Functional analysis indicated that the differentially expressed genes (DEGs) were involved in several biological processes, including developmental process, biological regulation and apoptotic process. A total of 15 candidate genes from the DEGs were screened using the ToppGene Suite. No significant differences in expression were observed between the RT-qPCR data and the microarray data. Transfection with ROP16 resulted in alterations of several biological processes, including nervous system development, apoptosis and transcriptional regulation. Several genes, including CXCL12, BAI1, ZIC2, RBMX, RASSF6, MAGE-A6 and HOX, were identified as significant DEGs. Taken together, these results may contribute to understanding the mechanisms underlying the functions of ROP16 and provide scope for further investigation of the pathogenesis of Toxoplasma gondii. PMID- 27666385 TI - Generalized reduced rank latent factor regression for high dimensional tensor fields, and neuroimaging-genetic applications. AB - We propose a generalized reduced rank latent factor regression model (GRRLF) for the analysis of tensor field responses and high dimensional covariates. The model is motivated by the need from imaging-genetic studies to identify genetic variants that are associated with brain imaging phenotypes, often in the form of high dimensional tensor fields. GRRLF identifies from the structure in the data the effective dimensionality of the data, and then jointly performs dimension reduction of the covariates, dynamic identification of latent factors, and nonparametric estimation of both covariate and latent response fields. After accounting for the latent and covariate effects, GRLLF performs a nonparametric test on the remaining factor of interest. GRRLF provides a better factorization of the signals compared with common solutions, and is less susceptible to overfitting because it exploits the effective dimensionality. The generality and the flexibility of GRRLF also allow various statistical models to be handled in a unified framework and solutions can be efficiently computed. Within the field of neuroimaging, it improves the sensitivity for weak signals and is a promising alternative to existing approaches. The operation of the framework is demonstrated with both synthetic datasets and a real-world neuroimaging example in which the effects of a set of genes on the structure of the brain at the voxel level were measured, and the results compared favorably with those from existing approaches. PMID- 27666390 TI - Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis. AB - Bats are an important reservoir for zoonotic viruses. To date, only three RVA strains have been reported in bats in Kenya and China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans. PMID- 27666389 TI - FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon. AB - Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Navs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons. PMID- 27666392 TI - A better state-of-mind: deep breathing reduces state anxiety and enhances test performance through regulating test cognitions in children. AB - A pre-test/post-test, intervention-versus-control experimental design was used to examine the effects, mechanisms and moderators of deep breathing on state anxiety and test performance in 122 Primary 5 students. Taking deep breaths before a timed math test significantly reduced self-reported feelings of anxiety and improved test performance. There was a statistical trend towards greater effectiveness in reducing state anxiety for boys compared to girls, and in enhancing test performance for students with higher autonomic reactivity in test like situations. The latter moderation was significant when comparing high-versus low autonomic reactivity groups. Mediation analyses suggest that deep breathing reduces state anxiety in test-like situations, creating a better state-of-mind by enhancing the regulation of adaptive-maladaptive thoughts during the test, allowing for better performance. The quick and simple technique can be easily learnt and effectively applied by most children to immediately alleviate some of the adverse effects of test anxiety on psychological well-being and academic performance. PMID- 27666391 TI - Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma. AB - Macrophage migration inhibitory factor (MIF) is highly expressed in glioblastoma, promoting malignant progression and suppresses immune surveillance. However, the mechanism underlying its biological roles in human glioblastoma and the capability of MIF to escape dendritic cell (DC) surveillance remain poorly understood. In the present study, we found that recombinant human MIF (rhMIF) activated the RhoA-ROCK1 pathway and simultaneously upregulated F-actin fibre formation. Additionally, we showed that rhMIF increased autophagy in glioblastoma cells, and knockdown of endogenic MIF suppressed autophagy. In glioma specimens, MIF expression was significantly correlated with LC3B levels. Moreover, we confirmed that the activity of Rho-associated coiled-coil containing kinase (ROCK)1 played a crucial role in MIF-induced autophagy. Y26736, a ROCK1 inhibitor, blocked the MIF-mediated increase in migration and colony formation in glioblastoma multiforme (GBM) cells. Furthermore, exogenous rhMIF suppressed the migration of both immature DCs (iDCs) and mature DCs (mDCs). Addition of rhMIF during the maturation process of iDCs impaired the expression of co-stimulatory markers. Taken together, our results identified ROCK1 as a critical mediator of MIF-induced autophagy and the immunosuppressive effect of MIF on DC surveillance in glioblastoma. PMID- 27666393 TI - Serum sclerostin levels in renal cell carcinoma patients with bone metastases. AB - Sclerostin has been proposed as a potent inhibitor of bone formation. Sclerostin antibodies are under clinical development to treat osteoporosis and metastatic bone disease. Serum sclerostin level is elevated in multiple myeloma, an osteolytic malignancy, where it might serve as predictive marker for the use of sclerostin-directed antibodies. As renal cell carcinoma (RCC) patients often present with osteolytic metastases, we aimed to investigate serum sclerostin levels in RCC patients. Our study included 53 RCC patients (19 with bone metastases, 25 with visceral metastases and 9 with localized disease) and 53 age- and gender-matched non-osteoporotic controls. Frozen serum samples were subjected to sclerostin quantitative sandwich ELISA. The mean serum sclerostin levels of RCC patients and controls were 45.8 pmol/l and 45.1 pmol/l, respectively (p = 0.86). Analysis of variance showed no difference between the subgroups of RCC patients with regard to visceral or bone metastases or localized disease (p = 0.22). There was no significant association between eGFR (estimated glomerular filtration rate) and serum sclerostin levels in RCC patients (r = 0.05; p = 0.74) and controls (r = 0.06; p = 0.68). Our results indicate that serum sclerostin levels appear not to be a valuable biomarker to assess the occurrence of bone metastases in RCC patients. PMID- 27666395 TI - Pharmacological Evaluation of Antiasthmatic Activity of Myrica nagi Bark Extracts. AB - BACKGROUND: The involvement of debilitating side effects of allopathic antiasthmatic drugs provides a strong impetus for the development of new herbal therapeutics. Myrica nagi Thunb. (Syn. Kaiphal) of Myricaceae family is a known drug of the Ayurveda system used for the treatment of several diseases including asthma. METHODS: The present study deals with the preparation and phytochemical screening of polar, non-polar and methanolic extracts of Myrica nagi bark followed by the evaluation of their antiasthmatic activity using four different animal experimental models: acetylcholine induced bronchospasm in conscious guinea pigs, acetylcholine induced contraction on isolated guinea pig tracheal chain preparation, compound 48/80 induced mast cell degranulation using rat, and trypsin and egg albumin induced bronchospasm in conscious rat. RESULTS: Polar extract of M. nagi bark (200 mg/kg, p.o.) exerted strong antiasthmatic effects near to Ketotifen (1 mg/kg, p.o) as standard drug. Polar extract of M. nagi bark (200 u.g/ml) significantly inhibited Ach induced contraction of isolated guinea pig tracheal chain preparation. Pre-incubation of rat peritoneal mast cells with test drugs (methanolic, non polar and polar extracts) showed dose dependent significant reduction of % mast cell degranulation. Polar extract (200mg/kg) & Methanolic extract (200mg/kg) of M. nagi bark treated animals showed significantly lesser serum bicarbonate level, higher tidal volume, lower level of eosinophils and neutrophils. CONCLUSION: The results of present investigation suggest that the polar extracts of Myrica nagi bark have better antiasthmatic activity than the non polar and methanolic extract. PMID- 27666394 TI - Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations. AB - Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses. PMID- 27666396 TI - Reduction of eNOS in Vascular Smooth Muscle by Salt Independently of Hypertension. AB - BACKGROUND: Endothelial nitric oxide synthase (eNOS) is known to be expressed in endothelium and smooth muscle cells of arteries. The aim of this study was to investigate the expression of eNOS in intimal and medial layer of aorta from rats fed a high salt diet and its modulation by losartan and tempol. METHODS: Rats were fed during three weeks with: normal salt diet (NS, 0.4% NaCl); high salt diet (HS, 8% NaCl); NS plus tempol 1 mM (NS-T); HS plus tempol (HS-T); NS plus losartan 40mg.kg-1 (NS-L) and HS plus losartan (HS-L). Systolic blood pressure was recorded by the tail cuff method. Rats were then anaesthetized and the thoracic aorta and small arteries (bronchial branches of aorta) were processed to evaluate the expression of eNOS and aquaporin-1 (AQP-1) by immunohistochemistry. RESULTS: HS group showed increased systolic blood pressure, increased eNOS and AQP-1 immunoexpression in the aorta intimal layer, and decreased eNOS immunoexpression in the aorta medial layer, respect to NS group. Losartan and tempol prevented hypertension and changes in the expression of eNOS and AQP-1 of the intimal layer. However, only tempol increased the expression of eNOS elicited by sodium overload in the medial layer of the aorta and small arteries respect to HS group. CONCLUSIONS: A high salt diet decreases eNOS expression in vascular smooth muscle layers of aorta and small arteries, which is reversed by tempol. These results suggest an adverse effect of oxidative stress on vascular eNOS in rats fed a high salt diet independently of hypertension. PMID- 27666397 TI - Zero Health Worker Infection: Experiences From the China Ebola Treatment Unit During the Ebola Epidemic in Liberia. AB - In November 2014, a total of 164 health care workers were dispatched by the Chinese government as the first medical assistance team to Liberia. The tasks of this team were to establish a China Ebola treatment unit (ETU), to commence the initial admission and treatment of suspected and confirmed Ebola patients, and to provide public health and infection control training for relevant local personnel. Overall, during the 2-month stay of this first medical assistance team in Liberia, 112 Ebola-suspected patients presented to the ETU, 65 patients were admitted, including 5 confirmed cases, and 3 confirmed cases were cured. Furthermore, 1520 local people were trained, including health care workers, military health care workers, staff members employed by the ETU, and community residents. Most importantly, as the first Chinese medical assistance team deployed to Liberia fighting the Ebola virus on the frontline, not a single member of this team or the hired local staff were infected by Ebola virus. This highly successful outcome was due to the meticulous infection control initiatives developed by the team, thereby making a significant contribution to China's ETU "zero infection" of health workers in Liberia. The major infection control initiatives conducted in the China ETU that contributed to achieving "zero infection" of all health workers in the ETU are introduced in this report. (Disaster Med Public Health Preparedness. 2017;11:262-266). PMID- 27666398 TI - Using a Human Factors Engineering Approach to Improve Patient Room Cleaning and Disinfection. PMID- 27666399 TI - Harvesting microalgal biomass using crossflow membrane filtration: critical flux, filtration performance, and fouling characterization. AB - The purpose of this study was to investigate the efficient harvesting of microalgal biomass through crossflow membrane filtration. The microalgal biomass harvesting experiments were performed using one microfiltration membrane (pore size: 0.2 um, made from polyvinylidene fluoride) and three ultrafiltration membranes (molecular weight cut-off: 150, 50, and 30 kDa, made from polyethersulfone, hydrophilic polyethersulfone, and regenerated cellulose, respectively). Initially, to minimize membrane fouling caused by microalgal cells, experiments with the objective of determining the critical flux were performed. Based on the critical flux calculations, the best performing membrane was confirmed to be the UH050 membrane, produced from hydrophilic polyethersulfone material. Furthermore, we also evaluated the effect of transmembrane pressure (TMP) and crossflow velocity (CFV) on filtration flux. It was observed that membrane fouling was affected not only by the membrane characteristics, but also by the TMP and CFV. In all the membranes, it was observed that increasing CFV was associated with increasing filtration flux, independent of the TMP. PMID- 27666400 TI - Exploring functional roles of TRPV1 intracellular domains with unstructured peptide-insertion screening. AB - TRPV1 is a polymodal nociceptor for diverse physical and chemical stimuli that interact with different parts of the channel protein. Recent cryo-EM studies revealed detailed channel structures, opening the door for mapping structural elements mediating activation by each stimulus. Towards this goal, here we have combined unstructured peptide-insertion screening (UPS) with electrophysiological and fluorescence recordings to explore structural and functional roles of the intracellular regions of TRPV1 in mediating various activation stimuli. We found that most of the tightly packed protein regions did not tolerate structural perturbation by UPS when tested, indicating that structural integrity of the intracellular region is critical. In agreement with previous reports, Ca2+ dependent desensitization is strongly dependent on both intracellular N- and C terminal domains; insertions of an unstructured peptide between these domains and the transmembrane core domain nearly eliminated Ca2+-dependent desensitization. In contrast, channel activations by capsaicin, low pH, divalent cations, and even heat are mostly intact in mutant channels containing the same insertions. These observations suggest that the transmembrane core domain of TRPV1, but not the intracellular domains, is responsible for sensing these stimuli. PMID- 27666401 TI - Topographic contrast of ultrathin cryo-sections for correlative super-resolution light and electron microscopy. AB - Fluorescence microscopy reveals molecular expression at nanometer resolution but lacks ultrastructural context information. This deficit often hinders a clear interpretation of results. Electron microscopy provides this contextual subcellular detail, but protein identification can often be problematic. Correlative light and electron microscopy produces complimentary information that expands our knowledge of protein expression in cells and tissue. Inherent methodological difficulties are however encountered when combining these two very different microscopy technologies. We present a quick, simple and reproducible method for protein localization by conventional and super-resolution light microscopy combined with platinum shadowing and scanning electron microscopy to obtain topographic contrast from the surface of ultrathin cryo-sections. We demonstrate protein distribution at nuclear pores and at mitochondrial and plasma membranes in the extended topographical landscape of tissue. PMID- 27666402 TI - MALDI-TOF-MS reveals differential N-linked plasma- and IgG-glycosylation profiles between mothers and their newborns. AB - During pregnancy, the mother provides multiple nutrients and substances to the foetus, with maternal immunoglobulin G (IgG) being actively transported to the foetus. Newborns depend on maternal IgG for immune-protection in their first months. The glycosylation of IgG has been shown to influence its dynamics, e.g. receptor binding. While minor differences in IgG glycosylation have been found between IgG derived from maternal blood and umbilical cord blood (UC) of newborn children, the differential glycosylation of maternal and UC plasma has hitherto not been studied. Here, we studied the N-glycosylation of IgG and total plasma proteome of both maternal and UC plasma of 42 pairs of mothers and newborn children. A total of 37 N-glycans were quantified for IgG and 45 for the total plasma N-glycome (TPNG). The study showed slightly higher levels of galactosylation for UC IgG than maternal IgG, confirming previous results, as well as lower bisection and sialylation. Furthermore, the TPNG results showed lower values for galactosylation and sialylation, and higher values for fucosylation in the UC plasma. In conclusion, this study presents some novel insights into IgG glycosylation differences as well as the first broad overview of the differential plasma glycosylation between mothers and newborns. PMID- 27666403 TI - The interaction of excited atoms and few-cycle laser pulses. AB - This work describes the first observations of the ionisation of neon in a metastable atomic state utilising a strong-field, few-cycle light pulse. We compare the observations to theoretical predictions based on the Ammosov-Delone Krainov (ADK) theory and a solution to the time-dependent Schrodinger equation (TDSE). The TDSE provides better agreement with the experimental data than the ADK theory. We optically pump the target atomic species and measure the ionisation rate as the a function of different steady-state populations in the fine structure of the target state which shows significant ionisation rate dependence on populations of spin-polarised states. The physical mechanism for this effect is unknown. PMID- 27666404 TI - A recurrent deletion in the SLC5A2 gene including the intron 7 branch site responsible for familial renal glucosuria. AB - Familial renal glycosuria (FRG) is caused by mutations in the SLC5A2 gene, which codes for Na+-glucose co-transporters 2 (SGLT2). The aim of this study was to analyze and identify the mutations in 16 patients from 8 families with FRG. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Six mutations in SLC5A2 gene were identified, including five missense mutations (c.393G > C, p.K131N; c.1003A > G, p.S335G; c.1343A > G, p.Q448R; c.1420G > C, p.A474P; c.1739G > A, p.G580D) and a 22-bp deletion in intron 7 (c.886(-10_-31)del) removing the putative branch point sequence. By the minigene studies using the pSPL3 plasmids, we confirmed that the deletion c.886(-10_-31)del acts as a splicing mutation. Furthermore, we found that this deletion causes exclusion of exon 8 in the SCL5A2 transcript in patients. The mutation c.886(-10_-31)del was present in 5 (62.5%) of 8 families, and accounts for about 37.5% of the total alleles (6/16). In conclusion, six mutations resulting in FRG were found, and the c.886(-10_-31)del may be the high frequency mutation that can be screened in FRG patients with uniallelic or negative SLC5A2 mutations. PMID- 27666405 TI - Asthma in children of Caribbean descent living in the inner-city: comparing Puerto Rican and Afro-Caribbean children. AB - Ethnic minority children bear a disproportionate amount of the US asthma burden. We compared asthma morbidity and pulmonary function (%FEV1) in two Caribbean groups living in the Bronx, NY: Puerto Rican and Afro-Caribbean children. Caregiver-child dyads (Puerto Rican: n = 113, M age = 9.89 +/- 2.05; Afro Caribbean: n = 47, Mage = 10.35 +/- 2.08) responded to sociodemographic and asthma-related questions, and children's %FEV1 was measured. Puerto Rican children had significantly greater (past year) asthma morbidity, yet there were no significant differences in %FEV1. This discrepancy between objective pulmonary function and asthma morbidity suggests the importance of considering sociocultural factors in pediatric asthma care. PMID- 27666408 TI - Functionalized and graft copolymers of chitosan and its pharmaceutical applications. AB - INTRODUCTION: Chitosan is the second most abundant natural polysaccharide. It belongs a family of polycationic polymers comprised of repetitive units of glucosamine and N-acetylglucosamine. Its biodegradability, nontoxicity, non immunogenicity and biocompatibility along with properties like mucoadhesion, fungistatic and bacteriogenic have made chitosan an appreciated polymer with numerous applications in the pharmaceutical, comestics and food industry. However, the limited solubility of chitosan at alkaline and neutral pH limits its widespread commercial use. This can be circumvented by fabrication of chitosan by graft copolymerization with acyl, alkyl, monomeric and polymeric moieties. Areas covered: Modifications like quarterization, thiolation, acylation and grafting result in copolymers with higher mucoadhesion strength, increased hydrophobic interactions (advantageous in hydrophobic drug entrapment), and increased solubility in alkaline pH, the ability for adsorption of metal ions, protein and peptide delivery and nutrient delivery. Insights on methods of polymerization, including atomic transfer radical polymerization and click chemistry are discussed. Applications of such modified chitosan copolymers in medical and surgical, and drug delivery, including nasal, oral and buccal delivery have also been covered. Expert opinion: Despite a number of successful investigations, commercialization of chitosan copolymers still remains a challenge. Further advancements in polymerization techniques may address the unmet needs of the healthcare industry. PMID- 27666409 TI - The incorporation site of Er in nanosized CaF2. AB - The incorporation site of Er dopants inserted at high and low concentration (respectively 5 and 0.5 mol%) in nanoparticles of CaF2 is studied by x-ray absorption spectroscopy (XAS) at the Er L III edge. The experimental data are compared with the results of structural modeling based on density functional theory (DFT). DFT-based molecular dynamics is also used to simulate complete theoretical EXAFS spectra of the model structures. The result is that Er substitutes for Ca in the structure and in the low concentration case the dopant ions are isolated. At high concentration the rare earth ions cluster together binding Ca vacancies. PMID- 27666407 TI - Depression accelerates the development of gastric cancer through reactive oxygen species-activated ABL1 (Review). AB - Depression is a common symptom among gastric cancer (GC) patients and serves as a potential indication of poor prognosis and advanced cancer clinical stage. However, the molecular mechanism of depression-associated poor prognoses of GC patients remains unclear. Recent studies have revealed that GC patients with depression are under high levels of oxidative stress (OS) status that is accompanied by the dysfunction of numerous proto-oncogenes, including the ABL proto-oncogene 1 (ABL1), which is a non-receptor tyrosine kinase. Recent evidence indicates that ABL1 was dysregulated in both major depressive disorder (MDD) and cancer patients with depression, and high levels of reactive oxygen species (ROS) can lead to the activation of ABL1 in response to OS and that activated ABL1 subsequently contributes to development of GC via interactions with the downstream targets and corresponding signaling pathways. In this review, we examine the evidence to illuminate the molecular mechanism of ABL1 in the progression of GC patients with depression and identify out new and effective methods for the initial and long-term treatment of GC. PMID- 27666406 TI - Telomere recombination pathways: tales of several unhappy marriages. AB - All happy families are alike; each unhappy family is unhappy in its own way.-Leo Tolstoy, Anna Karenina. PMID- 27666411 TI - A Gastrointestinally Digested Ribes nigrum L. Fruit Extract Inhibits Inflammatory Response in a Co-culture Model of Intestinal Caco-2 Cells and RAW264.7 Macrophages. AB - Blackcurrant fruits are a rich source of polyphenolic compounds with high antioxidant capacity and potent anti-inflammatory properties. In this study, blackcurrant extract digested in an artificial gastrointestinal tract and its intestinal permeable fraction were investigated for their ability to suppress inflammatory responses induced in a two-component cell culture system of intestinal epithelial cells and macrophages. The obtained results showed the capacity of the extract at a concentration of 1 mg of freeze-dried blackcurrant powder per mL to down-regulate the expression of inflammatory mediators, such as IL-8 (54 +/- 7%) and COX-2 (17 +/- 6%) in intestinal cells and IL-1alpha (76 +/- 4%), IL-1beta (91 +/- 2%), and IL-6 (61 +/- 5%) in macrophages stimulated with lipopolysaccharides. Inhibited COX-2 (44 +/- 6%) and iNOS (15 +/- 7%) expression played a role in reducing the production of prostaglandin E2 (40 +/- 20%) and NO (31 +/- 9%), respectively. Decreased TNF-alpha secretion (24 +/- 5%) by activated macrophages was also observed after treatment with blackcurrant extract. Moreover, the gastrointestinal-digested extract (0.01-1 mg/mL) dose dependently decreased the enhanced ROS generation (14-54%) and oxidative DNA damage (16-37%) induced in intestinal cells. The increased intestinal permeability caused by proinflammatory mediators, as assessed by transepithelial electrical resistance, was completely counteracted. PMID- 27666412 TI - Colorectal cancer cell-derived microRNA200 modulates the resistance of adjacent blood endothelial barriers in vitro. AB - Since cancer cells, when grown as spheroids, display drug sensitivity and radiation resistance patterns such as seen in vivo we recently established a three-dimensional (3D) in vitro model recapitulating colorectal cancer (CRC) triggered lymphatic endothelial cell (LEC)-barrier breaching to study mechanisms of intra-/extravasation. CRC metastasizes not only through lymphatics but also through blood vessels and here we extend the 3D model to the interaction of blood endothelial cells (BECs) with naive and 5-fluorouracil (5-FU)-resistant CRC CCL227 cells. The 3D model enabled quantifying effects of tumour-derived microRNA200 (miR200) miR200a, miR200b, miR200c, miR141 and miR429 regarding the induction of so-called 'circular chemorepellent-induced defects' (CCIDs) within the BEC-barrier, which resemble gates for tumour transmigration. For this, miR200 precursors were individually transfected and furthermore, the modulation of ZEB family expression was analysed by western blotting. miR200c, miR141 and miR429, which are contained in exosomes from naive CCL227 cells, downregulated the expression of ZEB2, SNAI and TWIST in BECs. The exosomes of 5-FU-resistant CCL227 RH cells, which are devoid of miR200, accelerated CCID formation in BEC monolayers as compared to exosomes from naive CCL227 cells. This confirmed the reported role of ZEB2 and SNAI in CRC metastasis and highlighted the active contribution of the stroma in the metastatic process. CCL227 spheroids affected the integrity of BEC and LEC barriers alike, which was in agreement with the observation that CRC metastasizes via blood stream (into the liver) as well as via lymphatics (into lymph nodes and lungs). This further validated the CRC/LEC and CRC/BEC in vitro model to study mechanisms of CRC spreading through vascular systems. Treatment of CCL227-RH cells with the HDAC inhibitors mocetinostat and sulforaphane reduced CCID formation to the level triggered by naive CCL227 spheroids, however, without significantly influencing miR200 expression in CCL227 RH cells. PMID- 27666413 TI - Sub-molecular modulation of a 4f driven Kondo resonance by surface-induced asymmetry. AB - Coupling between a magnetic impurity and an external bath can give rise to many body quantum phenomena, including Kondo and Hund's impurity states in metals, and Yu-Shiba-Rusinov states in superconductors. While advances have been made in probing the magnetic properties of d-shell impurities on surfaces, the confinement of f orbitals makes them difficult to access directly. Here we show that a 4f driven Kondo resonance can be modulated spatially by asymmetric coupling between a metallic surface and a molecule containing a 4f-like moment. Strong hybridization of dysprosium double-decker phthalocyanine with Cu(001) induces Kondo screening of the central magnetic moment. Misalignment between the symmetry axes of the molecule and the surface induces asymmetry in the molecule's electronic structure, spatially mediating electronic access to the magnetic moment through the Kondo resonance. This work demonstrates the important role that molecular ligands have in mediating electronic and magnetic coupling and in accessing many-body quantum states. PMID- 27666415 TI - Remote Optically Controlled Modulation of Catalytic Properties of Nanoparticles through Reconfiguration of the Inorganic/Organic Interface. AB - We introduce here a concept of remote photoinitiated reconfiguration of ligands adsorbed onto a nanocatalyst surface to enable reversible modulation of the catalytic activity. This is demonstrated by using peptide-ligand-capped Au nanoparticles with a photoswitchable azobenzene unit integrated into the biomolecular ligand. Optical switching of the azobenzene isomerization state drives rearrangement of the ligand layer, substantially changing the accessibility and subsequent catalytic activity of the underlying metal surface. The catalytic activity was probed using 4-nitrophenol reduction as a model reaction, where both the position of the photoswitch in the peptide sequence and its isomerization state affected the catalytic activity of the nanoparticles. Reversible switching of the isomerization state produces reversible changes in catalytic activity via reconfiguration of the biomolecular overlayer. These results provide a pathway to catalytic materials whose activity can be remotely modulated, which could be important for multistep chemical transformations that can be accessed via nanoparticle-based catalytic systems. PMID- 27666416 TI - Optical Monitoring of the Capillary Filling Dynamics Variation in Nanoporous Anodic Alumina toward Sensing Applications. AB - Fluid imbibition-coupled laser interferometry (FICLI) is a technique in which the kinetics of a fluid infiltrating a nanoporous anodic alumina (NAA) membrane is monitored by the interference of a laser beam at the membrane top and bottom surfaces. Further processing of the measured data results in an estimate of the pore radius. In this work, we study the accuracy of FICLI in the detection of small changes in pore radius, and we evaluate the possibility of using such detection as a sensing paradigm. The accuracy is estimated by measuring samples with increasing pore radius, obtained by successive wet etching steps, and repeatability is evaluated by using different liquids. For decreasing pore radius, samples obtained by the successive deposition of polyelectrolyte double layers are used. With the aim of evaluating the possibility of the FICLI method to sense biological binding events, BSA attachment detection is demonstrated by applying FICLI to samples before and after immobilization of the protein. Results show that the technique permits an accurate estimation of the pore radius, the pore-etching rate (with a radius variation of retch,DI = 1.05 nm/min +/- 0.11 nm/min), and the polyelectrolyte double layer thickness (with a radius variation of rPAH/PSS = 3.2 nm +/- 0.2 nm per polyelectrolyte double layer). Furthermore, the pore radius reduction measured after BSA immobilization (dBSA = 4.9 nm +/- 1.1 nm) is in good agreement with the protein size, as reported in the literature. With these results, we provide a sound basis for the applicability of FICLI as a sensitive technique for the characterization of NAA pore radius modifications. PMID- 27666414 TI - Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation. AB - Bioorthogonal labeling of antibodies enables the conjugation of compounds, such as small molecules or peptides, which expand targeting capacity or enhance cytotoxicity. Taking advantage of a cyclohexene sulfonamide compound that site selectively labels Lys64 in human serum albumin (HSA), we demonstrate that domain I of HSA can be used as a fusion protein for the preparation of antibody conjugates. Trastuzumab fusions were expressed at the N-terminus of the light chain or the C-terminus of the heavy chain enabling conjugation to small molecules. Moreover, these conjugates retained HER2 binding and proved to be highly stable in human plasma. Antibody conjugation via HSA domain I fusion should therefore have broad utility for making serum-stable antibody conjugates, particularly for antibody-drug conjugates. PMID- 27666417 TI - Microvirgula curvata sp. nov., isolated from hydrocarbon-contaminated soil, and emended description of the genus Microvirgula. AB - A novel Gram-stain-negative, small curved-rod-shaped, motile strain, designated L6T, was isolated from hydrocarbon-contaminated soils collected from Kuwait. Strain L6T was able to grow at 10-40 degrees C (optimum, 27-32 degrees C), pH 6.1-8.8 (optimum, 6.5-7.5) and 0-4.5 % (w/v) NaCl (optimum, 0-0.5). C18 : 1omega6c/C18 : 1omega7c, C16 : 0, C16 : 1omega6c/C16 : 1omega7c, C12 : 0 and C12 : 0 3-OH were predominant fatty acids with minor amounts of C14 : 0 and C17 : 0 cyclo. Phosphatidylglycerol and phosphatidylethanolamine were major polar lipids. The genomic G+C content was 61.2 mol%. 16S rRNA gene sequence comparisons indicated that strain L6T represents a member of the genus Microvirgula within the family Neisseriaceae of the class Betaproteobacteria. Strain L6T has a sequence similarity of 99.2 % with Microvirgula aerodenitrificans SGLY2T and <93.8 % with other members of the family Neisseriaceae. However, strain L6T showed only 56.5+/-2 % relatedness (based on DNA-DNA hybridization) with M. aerodenitrificans KACC 12055T (=SGLY2T). Distinct morphological, physiological and genotypic differences from the previously described taxa support the classification of strain L6T as a representative of a novel species in the genus Microvirgula, for which the name Microvirgula curvata sp. nov. is proposed. The type strain is L6T (=KEMB 2255-471T=JCM 31223T). An emended description of the genus Microvirgula is also proposed. PMID- 27666418 TI - Implementation of a 'care bundle' improves the management of patients admitted to hospital with decompensated cirrhosis. AB - BACKGROUND: Since 1970, there has been a 400% increase in liver-related deaths due to the increasing prevalence of chronic liver disease in the United Kingdom (UK). The 2013 UK National Confidential Enquiry into Patient Outcome and Death report found that only 47% of patients who died from alcohol-related liver disease received 'good care' during their hospital stay. AIM: To develop a 'care bundle' for patients with decompensated cirrhosis, aiming to ensure that evidence based treatments are delivered within the first 24 h of hospital admission. METHODS: This work gives practical advice about how to implement the bundle and examines its effects on patient care at three National Health Service Hospital Trusts in the UK by collecting data on patient care before and after introduction of the bundle. RESULTS: Data were collected on 228 patients across three centres (59% male, median age 53 years). Alcohol-related liver disease was the aetiology of chronic liver disease in 85% of patients. The overall mortality rate during hospital admission was 15%. The audits demonstrated improvements in patient care for patients with a completed care bundle who were significantly more likely to have a diagnostic ascitic performed within the first 24 h (P = 0.020), have an accurate alcohol history documented (P < 0.0001) and be given antibiotics as prophylaxis against infection following a variceal haemorrhage (P = 0.0096). In Newcastle, the bundle completion rate increased from 25% to 90% during the review periods. CONCLUSIONS: The introduction of a care bundle was associated with increased rates of diagnostic paracentesis and antibiotic prophylaxis with variceal haemorrhage in patients with decompensated cirrhosis. PMID- 27666419 TI - Cysteine-rich 61 RNA interference inhibits pathological angiogenesis via the phosphatidylinositol 3-kinase/Akt-vascular endothelial growth factor signaling pathway in endothelial cells. AB - Hypoxia is a key factor in the pathogenesis of angiogenesis, and cysteine-rich 61 (CCN1), an angiogenic factor, is involved in the development of pathological angiogenesis. The aim of the present study was to investigate the mechanism of CCN1 RNA interference (RNAi)-induced inhibition of hypoxia-induced pathological angiogenesis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions in vitro. The effects of inhibiting phosphoinositide 3-kinase (PI3K)/Akt signaling using LY294002 were investigated in hypoxic HUVECs. The proliferation and apoptosis of HUVECs under hypoxia were assessed using CCN1 RNAi. The CCN1-PI3K/Akt-vascular endothelial growth factor (VEGF) pathway was analyzed under hypoxic conditions using reverse transcription-quantitative polymerase chain reaction and western blotting. CCN1 RNAi inhibited the proliferation and induced the apoptosis of the HUVECs under hypoxia, with hypoxia significantly increasing the mRNA and protein expression levels of CCN1, Akt and VEGF. By contrast, CCN1 RNAi reduced the mRNA and protein expression levels of CCN1, Akt and VEGF in the HUVECs (P<0.05). Furthermore, LY294002 reduced the mRNA and protein expression levels of CCN1 in the hypoxic cells (P<0.05). These data indicated that CCN1 inhibits apoptosis and promotes proliferation in HUVECs. Therefore, CCN1 RNAi may offer a novel therapeutic strategy, which may aid in the treatment of pathological angiogenesis via inhibition of the PI3K/Akt-VEGF pathway. PMID- 27666420 TI - Evaluation of the sacral nerve plexus in pelvic endometriosis by three dimensional MR neurography. AB - PURPOSE: To investigate the feasibility of three-dimensional MR neurography (3D MRN) for the sacral plexus using sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences, and to demonstrate structural abnormalities in the pelvic nerve of women with pelvic endometriosis. MATERIALS AND METHODS: Twenty patients with pelvic endometriosis and 20 healthy controls were examined by contrast-enhanced 3D short time inversion recovery T2-weighted imaging (CE 3D STIR T2WI) SPACE sequences on 3 Tesla MRI. Image quality and diagnostic confidence of the sequences in identifying abnormalities of the sacral plexus were analyzed and compared with conventional three-plane images of 2D turbo-spin echo T2-weighted images (2D TSE T2WI). The changes in the sacral plexus caused by endometrial lesions were evaluated. RESULTS: The sacral plexus was clearly revealed in both healthy controls and patients with endometriosis on 3D STIR SPACE images. A good agreement was reached in the evaluation of both imaging quality (Kappa value [kappa] = 0.73-1.00) and diagnostic confidence (kappa = 0.66-0.81) when compared between the two independent readers. Abnormalities caused by endometriosis were identified in 17 patients, unilaterally in 10 patients, and bilaterally in 7 patients. Nerve fiber abnormalities of lumbar 5 (L5) were detected in 11 patients, of sacral 1 (S1) in 14 patients and of sacral 2 (S2) in 9 patients. CONCLUSION: CE 3D STIR SPACE sequences demonstrate its significant capacity to investigate and map the sacral plexus, and reveal the compression and adhesion of the sacral plexus nerve as a result of ectopic lesions. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:1225-1231. PMID- 27666422 TI - Generation of an 4-Isoxazolyl Anion Species: Facile Access to Multifunctionalized Isoxazoles. AB - A direct functionalization of unsubstituted isoxazole (1) was achieved by generation of 4-isoxazolyl anion species (3). An efficient 4-iodination of isoxazole and halogen-metal exchange reaction using a turbo Grignard reagent (iPrMgCl? LiCl) were essential for the generation of 3, which reacted with various electrophiles to give 4-functionalized isoxazoles in good to high yields. Isoxazolyl boronate, boronic acid, and stannane were also synthesized as useful building blocks from 1. The current methods enabled us to synthesize multi functionalized isoxazoles by introducing each substituent into the desired positions. Furthermore, total synthesis of triumferol, which was isolated from Triumfetta rhomboidea, was achieved from 1 in only three steps. PMID- 27666421 TI - Ru(II) complexes bearing guanidinium ligands as potent anticancer agents. AB - Two ruthenium(II) complexes containing guanidinium ligands have been synthesized and characterized for the first time. It was found that the two complexes exhibit moderate antitumor activity in Hela, A549, CNE-2, MCF-7, and HepG2 human tumor cells. Flow cytometric analysis showed that both complexes arrested the cell cycle in the G2/M phase and induced apoptosis in Hela cells. Mechanism studies indicate that both complexes induced apoptosis through caspase- and reactive oxygen species (ROS)-dependent pathways. Additionally, the two complexes displayed higher phototoxicity to tumor cells and almost no influence on normal liver LO2 cells upon irradiation at 450nm. PMID- 27666423 TI - Fine needle aspiration cytology of IgG4-related disease: A potential diagnostic pitfall? AB - BACKGROUND: IgG4-related disease (IgG4-RD) is a tumefactive fibro-inflammatory lesion that can affect any organ system in the body. Till date, no cytological data on IgG4-RD are available and this is the first study depicting the cytopathology features of IgG4-RD. AIM AND OBJECTIVE: To describe the cytopathological features and potential diagnostic errors of IgG4-RD. MATERIALS AND METHODS: The cytological features of 10 histopathology proven IgG4-RD cases (11 samples) were retrospectively reviewed along with corresponding histopathology. RESULTS: The cellularity of the cytology smears was low (36.4%) to moderate (45.4%) to high (18.1%). The low cellularity correlated well with the pattern C in histopathology (predominant fibrosis pattern). The non-epithelial background showed a preponderance of lymphocytes along with polymorphs and spindle-shaped fibroblasts. Most of these cases showed the presence of plasma cells and eosinophils. Epithelial atypia was seen in 18.2% cases. CONCLUSION: The causes of misdiagnosis were low cellularity, epithelial atypia, and non representative background. The important diagnostic clues to suspect a diagnosis of IgG4-RD include low cellularity despite adequate effort, inflammatory background rich in lymphocytes and spindle cells admixed with a few plasma cells and eosinophils along with radiological features and raised serum IgG4 Diagn. Cytopathol. 2017;45:14-21. (c) 2016 Wiley Periodicals, Inc. PMID- 27666424 TI - Physical fitness in preschool children: association with sex, age and weight status. AB - BACKGROUND: Because fitness level is a potent biomarker of health from an early age, the improvements of physical fitness performance through the promotion of physical activity could be important for the health of preschool children, particularly in obesity prevention. OBJECTIVE: The purpose of this study is to determine the physical fitness in children aged 3-6 years, discriminating performance by sex, age and body mass index (BMI). METHOD: A total of 3868 children from 3 to 6 years agreed voluntarily to participate. Demographic characteristics revealed that 1961 children were male (age: 55.71 +/- 11.11 months old, BMI = 16.03 +/- 1.93 kg/m2 ), and 1907 were female (age 56.16 +/- 0.97 months old, BMI = 15.85 +/- 1.89 kg/m2 ), and they were selected from 51 schools in southern Spain. RESULTS: Significant differences were found between sexes: boys showed a greater performance on cardio respiratory endurance, reaction time, strength and running speed. We found significant differences by sex in the different age groups (3, 4, 5 and 6 years old). CONCLUSIONS: Sex differences in physical fitness are evident at an early age; in addition, the relationship between physical fitness and BMI is inconsistent in preschool children. The improvements of physical fitness performance and its association with physical activity could be important for the health of children, particularly in obesity prevention. PMID- 27666426 TI - Case of primary cutaneous methotrexate-associated Hodgkin's lymphoma. PMID- 27666427 TI - Real-life use of vasopressors and inotropes in cardiogenic shock-observation is necessarily 'theory-laden'. PMID- 27666425 TI - HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption. AB - OBJECTIVE: Oxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA) related genetic risk factors for carbamazepine-induced cADRs have been identified. However, the HLA-related genetic risk factors associated with OXC induced cADRs are unknown. METHODS: A total of 40 patients who experienced OXC induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high-resolution HLA genotyping was performed. RESULTS: The HLA-B*40:02 and HLA-DRB1*04:03 alleles were significantly associated with OXC-induced MPE compared with the OXC-tolerant group (odds ratio [OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population (OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA-B*15:01 genetic frequency was significantly lower in the OXC-MPE group compared to the OXC-tolerant group (OR 0.18, p = 0.016) and the Korean population (OR 0.22, p = 0.030). The allele frequencies of well-known HLA-related risk factors for carbamazepine-induced cADRs (HLA-B*15:02, A*31:01 and B*15:11) were not different among the three groups. SIGNIFICANCE: This study is the first to demonstrate an association of HLA-B*40:02 and HLA-DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC-induced MPE. These findings should be confirmed in future studies in different ethnic groups. PMID- 27666428 TI - Climate change in cardiothoracic intensive care. PMID- 27666430 TI - Matrix Metalloproteinase 20 Co-expression With Dentin Sialophosphoprotein in Human and Monkey Kidneys. AB - We recently reported the expression of matrix metalloproteinase 20 (MMP20), hitherto thought to be tooth specific, in the metabolically active ductal epithelial cells of human salivary glands. Furthermore, our report indicated that MMP20 co-expressed and potentially interacts with dentin sialophosphoprotein (DSPP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Our earlier reports have shown the co-expression of three MMPs, MMP2, MMP3, and MMP9, with specific members of the SIBLING family: bone sialoprotein, osteopontin, and dentin matrix protein 1, respectively. This study investigated the expression of MMP20 and verified its co-expression with DSPP in human and monkey kidney sections and human mixed renal cells by IHC, in situ proximity ligation assay, and immunofluorescence. Our results show that MMP20 is expressed in all segments of the human and monkey nephron with marked intensity in the proximal and distal tubules, and was absent in the glomeruli. Furthermore, MMP20 co-expressed with DSPP in the proximal, distal, and collecting tubules, and in mixed renal cells. Consistent with other SIBLING-MMP pairs, the DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. PMID- 27666429 TI - Localization of Minodronate in Mouse Femora Through Isotope Microscopy. AB - Minodronate is highlighted for its marked and sustained effects on osteoporotic bones. To determine the duration of minodronate's effects, we have assessed the localization of the drug in mouse bones through isotope microscopy, after labeling it with a stable nitrogen isotope ([(15)N]-minodronate). In addition, minodronate-treated bones were assessed by histochemistry and transmission electron microscopy (TEM). Eight-week-old male ICR mice received [(15)N] minodronate (1 mg/kg) intravenously and were sacrificed after 3 hr, 24 hr, 1 week, and 1 month. Isotope microscopy showed that [(15)N]-minodronate was present mainly beneath osteoblasts rather than nearby osteoclasts. At 3 hr after minodronate administration, histochemistry and TEM showed osteoclasts with well developed ruffled borders. However, osteoclasts were roughly attached to the bone surfaces and did not feature ruffled borders at 24 hr after minodronate administration. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts and alkaline phosphatase-reactive osteoblastic area were not reduced suddenly, and apoptotic osteoclasts appeared in 1 week and 1 month after the injections. Von Kossa staining demonstrated that osteoclasts treated with minodronate did not incorporate mineralized bone matrix. Taken together, minodronate accumulates in bone underneath osteoblasts rather than under bone resorbing osteoclasts; therefore, it is likely that the minodronate-coated bone matrix is resistant to osteoclastic resorption, which results in a long-lasting and bone-preserving effect. PMID- 27666431 TI - Clinical significance and functional validation of PPA1 in various tumors. AB - The aim of the study was to detect PPA1 expression in various tumors and to investigate the relationship between PPA1 expression and clinicopathological parameters to further analyze its clinical significance. Immunohistochemical staining detected PPA1 expression in 305 noncancerous tissues and 675 tumor tissues, which included 12 different tumor types. QPCR and western blot examined PPA1 expression in tumor-derived cell lines including those derived from liver, breast, lung, and ovarian cancers. Cell proliferation and apoptosis assays were used to investigate PPA1-regulated cell growth in tumor cells. Finally, a bioinformatics analysis was used to verify the role of PPA1 in carcinogenesis. Among the 12 types of tumors, PPA1 expression was significantly higher in lung and ovarian cancers (P < 0.001). In lung cancer, PPA1 expression was associated with tumor size, patients' age, and smoking status, whereas in ovarian cancer, PPA1 expression was associated with pathological grade (P < 0.05). Moreover, we found that PPA1 expression was up-regulated in lung and ovarian cancer cell lines compared with nontumor cells. In addition, suppression of PPA1 expression by RNA interference in lung and ovarian cancer cells showed increased cell apoptosis and decreased cell proliferation, which was mediated by TP53 and p21 signaling. Notably, a bioinformatics analysis was used to verify the function of PPA1 in the development and progression of tumors. PPA1 expression is significantly higher in many tumors, especially those of lung and ovarian origin, which suggests that PPA1 plays an important role in carcinogenesis and in the development of some tumors. PMID- 27666433 TI - Macrocyclization in the Design of Organic n-Type Electronic Materials. AB - Here, we compare analogous cyclic and acyclic pi-conjugated molecules as n-type electronic materials and find that the cyclic molecules have numerous benefits in organic photovoltaics. This is the first report of such a direct comparison. We designed two conjugated cycles for this study. Each comprises four subunits: one combines four electron-accepting, redox-active, diphenyl-perylenediimide subunits, and the other alternates two electron-donating bithiophene units with two diphenyl-perylenediimide units. We compare the macrocycles to acyclic versions of these molecules and find that, relative to the acyclic analogs, the conjugated macrocycles have bathochromically shifted UV-vis absorbances and are more easily reduced. In blended films, macrocycle-based devices show higher electron mobility and good morphology. All of these factors contribute to the more than doubling of the power conversion efficiency observed in organic photovoltaic devices with these macrocycles as the n-type, electron transporting material. This study highlights the importance of geometric design in creating new molecular semiconductors. The ease with which we can design and tune the electronic properties of these cyclic structures charts a clear path to creating a new family of cyclic, conjugated molecules as electron transporting materials in optoelectronic and electronic devices. PMID- 27666432 TI - Upbeat nystagmus after bilateral superior canal plugging: A peripheral cause of vertical nystagmus. AB - Vertical nystagmus without a torsional component is generally considered a finding indicative of central nervous system pathology. We report two cases of purely upbeat nystagmus elicited with mastoid vibration after bilateral superior canal plugging, to highlight the vestibular pathophysiology involved in this unusual peripheral cause for upbeat nystagmus. Laryngoscope, 127:1698-1700, 2017. PMID- 27666434 TI - Production of a truncated recombinant HA1 for influenza A H9 subtype screening. AB - Hemagglutinin is the major component of membrane protein and plays a major role in virus entry into host cells through their receptors and it is predicted to elicit the production neutralizing antibodies. Our aim is to assess the potential of a truncated rHA1 domain, encoding residues 157-260 to detect influenza A H9 specific antibodies. The predicted characteristics of this protein revealed that it is a hydrophobic protein possessing predominant antigenicity and composed of random coils (48%) and extended strand (28%) but few alpha-helix (6.33%) and beta sheet (7%). A 312 pb HA1 gene was amplified and cloned in pET23b(+) vector including an C-terminal polyHis as a fusion partner, transformed and expressed in Escherichia coli cells as inclusion bodies. The truncated protein was solubilized with 8 M urea, purified by immobilized metal affinity chromatography and then detected by western blot with anti-His and H9-specific polyclonal antibodies. The test demonstrated high specificity (100%) and sensibility (98%). The immunoreactivity of the truncated rHA1 assessed revealed that only antisera against H9 yielded a specific and strong reactivity, with no cross-reactivity against negative sera. This study demonstrates that the truncated rHA1 may serve as a useful tool for rapid and easy surveillance of H9 infection. PMID- 27666435 TI - Development and application of HPLC-RI and HPLC-MS/MS based methods for quantification of residual deoxycholate levels in pneumococcal polysaccharides. AB - The analysis of residual sodium deoxycholate (DOC); a detergent of biological origin used in manufacturing of polysaccharide vaccines is challenging due to complex sample matrices and the lack of suitable methods. Here we report, rapid and sensitive high-performance liquid chromatography-refractive index (HPLC-RI) and tandem mass spectrometry (HPLC-MS/MS) methods for estimation of residual DOC in pneumococcal polysaccharides. For HPLC-RI method, separation was achieved using Luna C18 column and mobile phase compositions of acetonitrile: methanol: 20 mM sodium acetate (60:05:35% v/v). For HPLC-MS/MS method, separation was achieved using a Hypersil BDS C18 column with gradient elution of methanol and water (0.1% formic acid). MS/MS method showed linearity (r2 = 0.997) over the range of 10-320 ng/mL with limits of detection (LOD) and lower limit of quantitation (LOQ) of 3 and 10 ng/mL respectively. Precision (% RSD) and accuracy (% recovery) for both methods were in the range of 0.74-8.29% and 82.33-117.86% respectively. Sample matrices interferences were addressed following novel sample clean-up method based on liquid-liquid extraction. Both methods enabled traceable quantitation of DOC in intermediate and purified pneumococcal polysaccharides of serotypes: 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F and 23F. PMID- 27666436 TI - Outcomes According to Breast Cancer Subtype in Patients Treated With Accelerated Partial Breast Irradiation. AB - BACKGROUND: The purpose of the study was to determine outcomes for patients treated with accelerated partial breast irradiation (APBI) on the basis of breast cancer subtype (BCST). PATIENTS AND METHODS: Our single-institution, institutional review board-approved APBI database was queried for patients who had complete testing results for the estrogen (ER), progesterone (PR), and HER2/neu receptors to determine outcomes for each BCST. Women were assigned as luminal A (LA), luminal B (LB), HER2, and basal BCST using their ER, PR, and HER2/neu receptor status. Degree of ER expression supplemented the receptor-based luminal BCST assignment. Two hundred seventy-eight patients had results for all 3 receptors (LA = 164 [59%], LB = 81 [29%], HER2 = 5 [2%], basal = 28 [10%]), which were submitted for analysis (ipsilateral breast tumor recurrence [IBTR], regional nodal failure, distant metastasis [DM], disease-free survival [DFS], cause specific survival [CSS], and overall survival [OS]). RESULTS: Median follow-up was 5.4 years (range, 0.1-12.4 years). Basal and HER2 subtype patients had higher histologic grades (Grade 3 = 75% vs. 10% LA/LB; P < .001), larger tumors (13.0 mm basal vs. 10.7 mm LA/LB; P = .059), and were more likely to receive chemotherapy (68% vs. 15% LA/LB; P < .001). Margin and nodal status were similar among BCSTs. At 5 years, IBTR rates were similar (1.8%, 2.9%, 0%, and 4.8%) for LA, LB, HER2, and basal subtypes, respectively (P = .62). DM was only seen in LA (2.9%) and LB (1.3%) (P = .83). DFS (95%-100%), CSS (97%-100%), and OS (80%-100%) were not statistically different (P = .97, .87, .46, respectively). CONCLUSION: Five-year local control rates after breast-conserving surgery, APBI, and appropriate systemic therapy are excellent for luminal, HER2, and basal phenotypes of early stage breast cancer; however, further study of receptor subtype effect on risk stratification in early-stage breast cancer is needed. PMID- 27666437 TI - Traceless Rhodium-Catalyzed Hydroacylation Using Alkyl Aldehydes: The Enantioselective Synthesis of beta-Aryl Ketones. AB - A one-pot three-step sequence involving Rh-catalyzed alkene hydroacylation, sulfide elimination and Rh-catalyzed aryl boronic acid conjugate addition gave products of traceless chelation-controlled hydroacylation employing alkyl aldehydes. The stereodefined beta-aryl ketones were obtained in good yields with excellent control of enantioselectivity. Good variation of all three reaction components is possible. PMID- 27666439 TI - Reactivity Descriptors for the Activity of Molecular MN4 Catalysts for the Oxygen Reduction Reaction. AB - Similarities are established between well-known reactivity descriptors of metal electrodes for their activity in the oxygen reduction reaction (ORR) and the reactivity of molecular catalysts, in particular macrocyclic MN4 metal complexes confined to electrode surfaces. We show that there is a correlation between the MIII /MII redox potential of MN4 chelates and the M-O2 binding energies. Specifically, the binding energy of O2 (and other O species) follows the MIII OH/MII redox transition for MnN4 and FeN4 chelates. The ORR volcano plot for MN4 catalysts is similar to that for metal catalysts: catalysts on the weak binding side (mostly CoN4 chelates) yield mainly H2 O2 as the product, with an ORR onset potential independent of the pH value on the NHE scale (and therefore pH dependent on the RHE scale); catalysts on the stronger binding side yield H2 O as the product with the expected pH-dependence on the NHE scale. The suggested descriptors also apply to heat-treated pyrolyzed MN4 catalysts. PMID- 27666438 TI - Disruption of a miR-29 binding site leading to COL4A1 upregulation causes pontine autosomal dominant microangiopathy with leukoencephalopathy. AB - OBJECTIVE: Cerebral small vessel disease (cSVD) is a heterogeneous group of disorders. Screening of known cSVD genes identifies the causative mutation in <15% of familial cSVD cases. We sought to identify novel causes of cSVD. METHODS: We used linkage analysis and exome sequencing to identify the causal mutation in a French cSVD family. The identified candidate gene was then screened in 202 cSVD unrelated probands, including 1 proband from the first reported pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL) family. Sanger sequencing was used to confirm variants in all mutated probands and analyze their segregation in probands' relatives. Mutation consequences were assessed with luciferase reporter assays and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: A candidate heterozygous variant located in a predicted miR 29 microRNA binding site, within the 3' untranslated region of COL4A1, was identified in the large French cSVD family. Five additional unrelated probands, including the PADMAL proband, harbored heterozygous variants in this microRNA binding site. Variants cosegregated with the affected phenotype, and cumulative logarithm of odds score reached 6.03, establishing linkage to this locus. A highly significant difference was observed when comparing the number of variants within this binding site in cases and controls (p = 1.77 * 10E-12). RT-qPCR analyses of patients' primary fibroblasts and luciferase reporter assays strongly favor an upregulation of COL4A1 mediated by disruption of miR-29 binding to its target site. Magnetic resonance imaging features were characterized by the presence of multiple pontine infarcts in all symptomatic mutation carriers. INTERPRETATION: Mutations upregulating COL4A1 expression lead to PADMAL, a severe early onset ischemic cSVD, distinct from the various phenotypes associated with COL4A1 missense glycine mutations. Ann Neurol 2016;80:741-753. PMID- 27666442 TI - A look at the future of vascular surgery. PMID- 27666440 TI - Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents. AB - Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naive patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. PMID- 27666441 TI - Cooperative Catalysis of Combined Systems of Transition-Metal Complexes with Lewis Acids: Theoretical Understanding. AB - The combination of transition-metal complexes and Lewis acids has been recently applied to several catalytic reactions, in which the Lewis acid plays a crucial role as a non-innocent additive to accelerate the reaction. In this review article, the reasons for the acceleration by the Lewis acid are discussed based on our recent theoretical studies. In the H-H sigma-bond activation of a dihydrogen molecule by a nickel(0)-borane complex, the empty p orbital of the borane moiety interacts with the H-H sigma bonding MO to form charge transfer (CT) from the dihydrogen molecule to the borane moiety to accelerate the reaction. In the B-F sigma-bond activation of BF3 by a platinum(0)-bisphosphine complex, the second BF3 molecule interacts with the F atom that is dissociating from the B atom to stabilize the transition state and product by the CT from the F atom to the second BF3 . In this reaction, the substrate BF3 plays a crucial role as the Lewis acid to accelerate the activation of the B-F sigma bond. In the nickel-catalyzed decyanative coupling of arylcarboxybenzonitriles with acetylenes, two molecules of the aluminum Lewis acid interact with the cyano N atom and the carbonyl O atom of the substrate to stabilize the transition state and intermediate. In the nickel-catalyzed alkylation of aromatic amides with alkenes, the Lewis acid enhances the para regioselectivity of alkylation by interacting with the carbonyl O atom. In the nickel-catalyzed carboxylation of sp3 carbon and sp carbon atoms with carbon dioxide, not the sigma-bond activation but the insertion reaction of carbon dioxide into the metal-carbon bond is accelerated by the Lewis acid by interacting with the O atom of carbon dioxide, because the CT from the metal-carbon bond to carbon dioxide is enhanced by the interaction. This theoretical knowledge suggests that the combination of transition-metal complex and Lewis acid can broaden the application range of transition-metal complex as catalyst. PMID- 27666443 TI - High proportion of known abdominal aortic aneurysm in patients with rupture indicates surveillance deficiency. AB - OBJECTIVE: This study assessed the proportion of previously known abdominal aortic aneurysm (AAA) in patients presenting with a ruptured AAA (rAAA) and analyzed the reasons for nontreatment at the time of the initial AAA diagnosis. METHODS: This retrospective, observational study included all patients with rAAA admitted to a hospital in the counties of Stockholm and Gotland during 2009 to 2013. The patients' records were retrospectively reviewed, with extraction of data on previously detected AAA, demographics, and mortality at 30 and 90 days. RESULTS: We identified 283 patients (76% men) with a mean age of 78.7 years. An AAA had been previously detected in 85 (30%). The overall mortality was higher (68% vs 53%; P = .018) and the intervention rate was lower in patients with a previously detected AAA (59% vs 82%, P < .001). The 90-day mortality rate for all treated rAAA was 43%. Reasons for nontreatment at the initial AAA detection were denial of elective surgery in 31 (36%), patient choice in 15 (18%), size-related in 11 (13%), and surveillance deficiency in 26 (31%). The latter group included patients who failed to comply, missed referral for computed tomography scans, and lack of follow-up of radiology reports. At the time of rupture, 22 patients (85%) were treated, with 30-day and 90-day mortality rates both at 41% (n = 9). CONCLUSIONS: One-third of patients admitted with a rAAA had a previously detected AAA. The surgeons' decision to deny elective surgery and surveillance deficiency were the two main reasons for nontreatment at time of the AAA diagnosis. Improved patient-specific protocols to reduce the surveillance gaps and new methods of determining rupture risk in each case of AAA could be two possible future strategies to reduce the incidence of rupture. PMID- 27666444 TI - Results of common femoral artery thromboendarterectomy evaluation of a traditional surgical management in the endovascular era. AB - OBJECTIVE: The aim of this study was to investigate the long-term outcome of common femoral artery thromboendarterectomy in patients with peripheral arterial occlusive disease. METHODS: The study retrospectively evaluated 713 vessels in 655 patients (75% male; mean age, 69.4 +/- 9.5 years) who underwent common femoral thromboendarterectomy from January 2006 until May 2012 in two high-volume vascular centers. Critical limb ischemia was present in 221 patients, and intermittent claudication was present in 434. Three patent tibial arteries, described as runoff vessels, were available in 33% of the cohort, two were present in 28.3%, one runoff vessel was present in 23.4%, and 15.2% (n = 102) showed no runoff option. Hybrid procedures were used to treat 255 limbs (35.8%). The primary end point was primary patency (PP). Secondary patency (SP), limb salvage, and survival were the secondary end points. RESULTS: Survival rates were 93.9%, 83.0%, 74.1%, and 60.1% at 1, 3, 5, and 7 years, respectively. PP was 78.5% and SP was 89.1% at 7 years. Patency rates were 97.3% (PP) and 97.8% (SP) at 6 months and 90.2% (PP) and 98.3% (SP) at 3 years, respectively, with 76 target lesion revascularizations. No significant difference was demonstrated for PP rates stratified for nonhybrid procedures and hybrid procedures (78.1% vs 78.6%; P = .22) and for critical limb ischemia vs intermittent claudication (76.3% vs 79.4%; P = .20) at 7 years. The mean +/- standard deviation ankle brachial index increased from 0.46 +/- 0.3 preoperatively to 0.81 +/- 0.2 postoperatively and to 0.77 +/- 0.3 at 7 years (P < .001). A total of 20 major amputations were performed, achieving a limb salvage rate of 92.6%. Procedure related complications occurred in 11.5% during 7 years of follow-up. CONCLUSIONS: Open surgery for common femoral artery stenosis is safe and effective in the long term. Endovascular therapy will need to compete with these excellent results. PMID- 27666445 TI - Invited commentary. PMID- 27666447 TI - Invited commentary. PMID- 27666446 TI - A depleting antibody toward sca-1 mitigates a surge of CD34(+)/c-kit(+) progenitors and reduces vascular restenosis in a murine vascular injury model. AB - OBJECTIVE: Vascular restenosis remains a major obstacle to long-term success after vascular intervention. Circulating progenitor cells have been implicated in restenosis, and yet it has remained unclear if these cells, particularly nonendothelial progenitors, have an active role in this pathologic process. We hypothesized that circulating CD34(+)/c-kit(+) progenitors would increase after vascular injury, mirrored by changes in the injury signal, stromal cell-derived factor 1alpha (sdf1alpha). We further postulated that an antibody-based depletion would mitigate progenitor surge and, in turn, reduce restenosis in a murine model. METHODS: C57BL6 mice underwent wire injury of the femoral artery and were compared with mice with sham surgery and vessel ligation by flow cytometry as well as by sdf1alpha enzyme-linked immunosorbent assay of peripheral blood. Next, injured C57BL6 mice treated with a depleting antibody toward the progenitor marker sca-1 or with an isotype control were compared in terms of sdf1alpha as well as enumeration of progenitors. At 28 days, restenosis was quantified between sca-1- and isotype-treated animals. RESULTS: Wire injury generated an increase in sdf1alpha as well as a surge of CD34(+)/c-kit(+) progenitors relative to nonsurgical controls (P = .005). Treatment with sca-1 antibody ablated the peripheral surge compared with isotype-treated, injured animals (P = .02), and sca progenitor depletion reduced the 28-day intima to media ratio in a statistically significant fashion compared with either nontreated (P = .04) or isotype-treated (P = .036) animals. CONCLUSIONS: Our study has demonstrated that sca-1 antibody reduces both progenitor surge and vascular restenosis after endoluminal vascular injury in a murine model. This suggests that circulating progenitors play an active role in restenotic disease. PMID- 27666448 TI - Invited commentary. PMID- 27666449 TI - Invited commentary. PMID- 27666450 TI - Hybrid treatment of thoracoabdominal aortic aneurysms with Marfan syndrome. PMID- 27666451 TI - Endograft component separation in giant hepatic artery aneurysm. PMID- 27666452 TI - Regarding "Anesthetic type and risk of myocardial infarction after carotid endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)". PMID- 27666453 TI - Reply. PMID- 27666454 TI - Regarding "Isolated superior mesenteric artery dissection in China". PMID- 27666455 TI - Reply. PMID- 27666456 TI - Regarding "The effect of an Enhanced Recovery Program in elective retroperitoneal abdominal aortic aneurysm repair". PMID- 27666457 TI - Reply. PMID- 27666458 TI - Regarding "Outcomes of arterial resection during pancreatectomy for tumor". PMID- 27666459 TI - Regarding "Prospective evaluation of postimplantation syndrome evolution on patient outcomes after endovascular aneurysm repair for abdominal aortic aneurysm". PMID- 27666460 TI - Reply. PMID- 27666461 TI - Reply. PMID- 27666462 TI - Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts. AB - Uridine 5'-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17beta as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P<0.01). Liver disorders, such as fatty liver and hepatitis, were observed in half cows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17beta glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows. PMID- 27666463 TI - CpG site DNA methylation patterns reveal a novel regulatory element in the mouse prion protein gene. AB - The cellular isoform of the prion protein (PrPC) plays critical roles in the development of prion disorders. Although PrP mRNA is ubiquitously present in a tissue-specific manner, the DNA methylation of PrP gene (Prnp) is still unknown. In this study, we demonstrated that the CpG island (CGI, positioned at -218 to +152 bp from the transcriptional start site) including the Prnp core promoter region was completely unmethylated in all tested tissues. On the other hand, CpG methylation in the CGI shore region (positioned at -599 to -238 bp) occurred in various tissue- and site-specific proportions. Interestingly, the correlation analysis between CpG methylation status and PrP mRNA levels showed that one CpG site methylation at -576 was negatively correlated with the PrP mRNA level (Pearson's r = -0.374, P=0.035). Taken together, our results suggest that Prnp is a typical housekeeping gene and various methylation frequencies of the CGI shore region are likely to affect Prnp expression in a tissue-specific manner. PMID- 27666465 TI - Assessing knowledge, motivation and perceptions about falls prevention among care staff in a residential aged care setting. AB - Falls are a serious problem in residential aged care settings. The aims of the study were to determine the feasibility of surveying care staff regarding falls prevention, and describe care staff levels of knowledge and awareness of residents' risk of falls, knowledge about falls prevention, motivation and confidence to implement falls prevention strategies. A custom designed questionnaire was administered to care staff at one site of a large residential aged care organization in Australia. The survey response was 58.8%. Feedback from staff was used to inform the administration of the survey to the wider organization. Seven (29.2%) care staff reported they were unsure or thought residents were at low risk of falls. Only five (20.8%) care staff were able to suggest more than three preventive strategies. These preliminary findings suggest that education to change care staff behavior regarding falls prevention should target improving care staff knowledge and awareness of falls. PMID- 27666464 TI - Prior exposure to Bordetella species as an exclusion criterion in the baboon model of pertussis. AB - The baboon model of Bordetella pertussis infection is the newest and most clinically accurate model of the human disease to date. However, among the 15 experimentally infected baboons in this study, a subset of baboons did not exhibit the expected high bacterial colonization levels or increase in white blood cell count. Moreover, cultures of nasopharyngeal wash samples from several baboons suggested B. bronchiseptica coinfection. Analysis of serum antibodies recognizing filamentous hemagglutinin, pertussis toxin and B. pertussis lipo oligosaccharide indicated that several baboons had likely been previously exposed to Bordetella species and that prior exposure correlated with partial protection from B. pertussis infection. Notably, all animals with a baseline Fha titer of 5 IU/ml or below exhibited symptoms typical of the model, suggesting this value can be used as inclusion criteria for animals prior to study enrollment. While B. pertussis infection is endemic to human populations and B. bronchiseptica is common in wild small mammals, this study illustrates that baboons can readily harbor both organisms. Awareness of Bordetella species that share antigens capable of generating protective immune responses and tracking of prior exposure to those species is required for successful use of the baboon model of pertussis. PMID- 27666466 TI - Juvenile myasthenia gravis in Norway: A nationwide epidemiological study. AB - BACKGROUND: The aim of this study was to assess the incidence rate and prevalence of autoimmune myasthenia gravis (MG) among children in Norway. METHODS: This retrospective population-based study was performed in Norway from January 2012 to December 2013. Cases of juvenile MG (JMG) with onset < 18 years were identified through searches in coding systems of electronic patient records at the 15 main hospitals in Norway from 1989 to 2013. In addition, the acetylcholine receptor antibody database at Haukeland University Hospital and the clinical nationwide MG database at Oslo University Hospital were searched for cases of JMG. Diagnosis and age at onset were verified through medical records. Incidence and prevalence rates were calculated using the Norwegian population as reference. RESULTS: In total 63 unique JMG cases were identified. This corresponds to an average annual incidence rate of 1.6 per million. Incidence rate was stable over the study period. Prevalence of JMG was 3.6-13.8 per million. Females constituted the majority of JMG cases (55 vs 8 males). The risk of JMG was higher among females both in the postpubertal and prepubertal group (p < 0.001 and p = 0.02, respectively). CONCLUSION: This study confirms the rarity of JMG in Norway, especially among males, and shows a stable incidence rate over the last 25 years. PMID- 27666467 TI - Morphology quiz: a 12-year-old child with a tumour in the neck. PMID- 27666468 TI - Determination of restless legs syndrome prevalence in children aged 13-16years in the provincial center of Kayseri. AB - OBJECTIVE: This study was conducted to determine the prevalence rate of restless legs syndrome (RLS) and associated factors in adolescents aged 13-16years in the provincial center of Kayseri. MATERIALS AND METHODS: The study sample included 5720 adolescents who were selected from among 74,421 grade 7-10 students aged 13 16years in the provincial center of Kayseri. Overall, datas from 4792 subjects were included into analysis. Data were collected by using a self reported questionnaire and the Epworth Sleepiness Scale (ESS). The prevalence rate of RLS was determined by questionnaire datas and phone interviews. The effects of age, gender, economical status and body weight on RLS prevalence rate were analyzed. Mean ESS score was calculated. The effect of RLS on academic success, as measured by grade point average, was also assessed. The subjects were stratified as underweight, normal, overweight and obese according to the body mass index and the RLS prevalence rate was compared among groups. RESULTS: The RLS prevalence rate was determined to be 2.9% among adolescents aged 13-16years in the study group. It was found that gender and economical status had no significant effect on RLS prevalence. Mean age at symptom onset was 11.4years of age. There was a positive family history in 11.3% of subjects. Mean body mass index (BMI) was found to be significantly higher in subjects with RLS (21.5+/-3.8 vs. 20.5+/ 3.2). Academic success (72.0+/-11.2 vs. 77.0+/-12.0) was found to be poorer and daytime sleepiness level, as measured by ESS (11.4+/-3.9 vs. 6.3+/-4.0), was found to be higher in subjects with RLS. CONCLUSION: The RLS prevalence rate was 2.9% in the study sample while gender and economical status had no significant effect on prevalence rate. The RLS, which results in decreased sleep quality and academic success, is an important disorder with a considerable prevalence in the population. PMID- 27666469 TI - CORRIGENDUM: Change in Ankle-Brachial Index Over Time in a Screened Japanese Cohort - The Okinawa Peripheral Arterial Disease Study. PMID- 27666472 TI - Heat-coping strategies and bedroom thermal satisfaction in New York City. AB - There has been little research into the thermal condition of the sleeping environment. Even less well documented and understood is how the sleeping thermal environment is affected by occupant behaviors such as the use of air-conditioning (AC) and electric fans, or window operations. In this paper we present results from a questionnaire survey administered to assess summertime bedroom thermal satisfaction and heat-coping strategies among New York City (NYC) residents. Specifically, we investigated current AC usage in bedrooms and examined alternate cooling strategies, cooling appliance usage patterns, and the motivations that drove these patterns during the 2015 summer. Among survey respondents (n=706), AC was the preferred heat-coping strategy, and for 30% of respondents was the only strategy used. Electric fan use and window opening were deemed ineffective for cooling by many respondents. Indeed, less than a quarter of all respondents ever opened windows to alleviate heat in their bedrooms. In general, people utilized strategies that modify the environment more than the individual person. Unsurprisingly, the frequency and overall use of AC were significantly associated with greater bedroom thermal satisfaction; however, setting AC to a lower temperature provided no additional benefit. In contrast, more frequent use of electric fans was associated with lower thermal satisfaction. In addition, 14.7% of all respondents did not have AC in their sleeping environment and 5.8% were without any AC at home. Despite the high penetration of AC ownership, usage cost was still a major concern for most. This work contributes to a better understanding of bedtime heat-coping strategies, cooling appliance usage patterns, and associated thermal satisfaction in NYC. The findings of this study suggest resident AC usage patterns may not be optimized for thermal satisfaction. Potential alternative cooling approaches could be explored to better balance maximizing thermal comfort while reducing energy consumption and environmental impact. PMID- 27666473 TI - Quantitative assessment of human health risk posed by polycyclic aromatic hydrocarbons in urban road dust. AB - Among the numerous pollutants present in urban road dust, polycyclic aromatic hydrocarbons (PAHs) are among the most toxic chemical pollutants and can pose cancer risk to humans. The primary aim of the study was to develop a quantitative model to assess the cancer risk from PAHs in urban road dust based on traffic and land use factors and thereby to characterise the risk posed by PAHs in fine (<150MUm) and coarse (>150MUm) particles. The risk posed by PAHs was quantified as incremental lifetime cancer risk (ILCR), which was modelled as a function of traffic volume and percentages of different urban land uses. The study outcomes highlighted the fact that cancer risk from PAHs in urban road dust is primarily influenced by PAHs associated with fine solids. Heavy PAHs with 5 to 6 benzene rings, especially dibenzo[a,h]anthracene (D[a]A) and benzo[a]pyrene (B[a]P) in the mixture contribute most to the risk. The quantitative model developed based on traffic and land use factors will contribute to informed decision making in relation to the management of risk posed by PAHs in urban road dust. PMID- 27666474 TI - The effect of drip irrigation and drip fertigation on N2O and NO emissions, water saving and grain yields in a maize field in the North China Plain. AB - N2O and NO emissions, the water usage and grain yields of a maize field in the North China Plain (NCP) under traditional flood irrigation, drip irrigation and drip fertigation were compared. With respect to the flood irrigation treatment, N2O emissions were reduced by 13.8% in the drip irrigation treatment and 7.7% in the drip fertigation treatment. NO emissions were reduced to 16.7% in the drip irrigation treatment but increased by 21.7% in the drip fertigation treatment. The molar ratios of NO/N2O within 2days after each fertilization event were evidently greater from the drip fertigation treatment than from the flood irrigation treatment, indicating that nitrification was more intensive in the drip fertigation treatment than in the treatment of flood irrigation. Compared with the flood irrigation treatment, evident increase of the maize yields in the drip irrigation treatment (28%) and the drip fertigation treatment (3.7%) were found. Although the drip fertigation treatment could evidently increase NO emission, the 40% water reduction in drip fertigation is of great importance for the sustainable development of agriculture in the NCP where water resources are extremely limited. To mitigate NO emissions from agricultural fields in the NCP with drip fertigation, the addition of a nitrification inhibitor combined with N or nitrate fertilizer was recommended. PMID- 27666475 TI - A decision analysis framework for estimating the potential hazards for drinking water resources of chemicals used in hydraulic fracturing fluids. AB - Despite growing concerns over the potential for hydraulic fracturing to impact drinking water resources, there are limited data available to identify chemicals used in hydraulic fracturing fluids that may pose public health concerns. In an effort to explore these potential hazards, a multi-criteria decision analysis (MCDA) framework was employed to analyze and rank selected subsets of these chemicals by integrating data on toxicity, frequency of use, and physicochemical properties that describe transport in water. Data used in this analysis were obtained from publicly available databases compiled by the United States Environmental Protection Agency (EPA) as part of a larger study on the potential impacts of hydraulic fracturing on drinking water. Starting with nationwide hydraulic fracturing chemical usage data from EPA's analysis of the FracFocus Chemical Disclosure Registry 1.0, MCDAs were performed on chemicals that had either noncancer toxicity values (n=37) or cancer-specific toxicity values (n=10). The noncancer MCDA was then repeated for subsets of chemicals reported in three representative states (Texas, n=31; Pennsylvania, n=18; and North Dakota, n=20). Within each MCDA, chemicals received scores based on relative toxicity, relative frequency of use, and physicochemical properties (mobility in water, volatility, persistence). Results show a relative ranking of these chemicals based on hazard potential, and provide preliminary insight into chemicals that may be more likely than others to impact drinking water resources. Comparison of nationwide versus state-specific analyses indicates regional differences in the chemicals that may be of more concern to drinking water resources, although many chemicals were commonly used and received similar overall hazard rankings. Several chemicals highlighted by these MCDAs have been reported in groundwater near areas of hydraulic fracturing activity. This approach is intended as a preliminary analysis, and represents one possible method for integrating data to explore potential public health impacts. PMID- 27666476 TI - Selection and antitumor activity of anti-Bcl-2 DNAzymes. AB - Apoptosis pathway has become one of the important targets for therapeutic exploration for cancer therapy. The increased Bcl-2 protein level and phosphorylation is implicated in a decreased chemotherapeutic response in many cancers. BCL-2 inhibitors have been developed as direct inducers of apoptosis. However, resistance to BCL2 inhibitors has been emerging and thus considerable effort has been made to seek novel approaches to BCL2 suppression. In this report we describe an in vitro DNAzyme selection strategy resulting in molecules that are effective in suppressing expression of the target gene BCL-2 in vitro. A 3' inverted modification was shown to significantly increase the DNAzyme stability in serum and the modified DNAzyme delivered by an osmotic pump chemosensitized human prostate cancer to Taxol in vivo. Thus this study provides an alternative strategy for potential BCL-2-targetd therapy. PMID- 27666477 TI - MOV10 interacts with Enterovirus 71 genomic 5'UTR and modulates viral replication. AB - As a cytoplasmic parasite, RNA virus develops sophisticated mechanisms to counter host defense and utilize host proteins to facilitate its replication. Here we found Moloney leukemia virus 10 (MOV10), a highly conserved cellular protein belonging to SF1 helicase family, played critical roles in EV71 infection. Silencing cellular MOV10 could restrict EV71 replication, while over-expressing MOV10 resulted in increased viral replication at low dosage and repressed viral replication at high dosage. Further investigation showed that MOV10 exhibited dual functions in EV71 regulation, its C-terminus positively regulated viral replication by binding to EV71 cloverleaf-like structure and the internal ribosome entry site while the N-terminus showed a potential antiviral activity when individually overexpressed. In addition, RNA-dependent interaction between MOV10 and HuR as well as the co-localization of MOV10 and processing bodies were also observed post infection. Taken together, our data indicate a crucial role of MOV10 in EV71 infection for the first time, providing new insights for its roles in EV71 infection. PMID- 27666478 TI - The unfolded protein response is a negative regulator of scavenger receptor class B, type I (SR-BI) expression. AB - Scavenger receptor class B, type I (SR-BI) is the main receptor for high-density lipoprotein (HDL) and an emerging atheroprotective candidate. A central function of SR-BI is the delivery of HDL-derived cholesterol to the liver for subsequent excretion into the bile. Here, we investigated the regulation of SR-BI by the unfolded protein response (UPR), an adaptive mechanism induced by endoplasmic reticulum (ER) stress, which is frequently activated in metabolic disorders. We provide evidence that induction of acute ER stress by well-characterized chemical inducers leads to decreased SR-BI expression in hepatocyte-derived cell lines. This results in a functional reduction of selective lipid uptake from HDL. However, the regulation of SR-BI by ER stress is not a direct consequence of altered cellular cholesterol metabolism. Finally, we show that SR-BI down regulation by the UPR might be a compensatory mechanism to provide partial adaption to ER stress. The observed down-regulation of SR-BI by ER stress in hepatic cells might contribute to the unfavorable effects of metabolic disorders on cholesterol homeostasis and cardiovascular diseases. PMID- 27666479 TI - Trifluoperazine blocks the human cardiac sodium channel, Nav1.5, independent of calmodulin. AB - Trifluoperazine is a phenothiazine derivative which is mainly used in the management of schizophrenia and also acts as a calmodulin inhibitor. We used the whole-cell patch-clamp technique to study the effects of trifluoperazine on human Nav1.5 (hNav1.5) currents expressed in HEK293 cells. The 50% inhibitory concentration of trifluoperazine was 15.5 +/- 0.3 MUM and the Hill coefficient was 2.7 +/- 0.1. The effects of trifluoperazine on hNav1.5 were completely and repeatedly reversible after washout. Trifluoperazine caused depolarizing shifts in the activation and hyperpolarizing shifts in the steady-state inactivation of hNav1.5. Trifluoperazine also showed strong use-dependent inhibition of hNav1.5. The blockade of hNav1.5 currents by trifluoperazine was not affected by the whole cell dialysis of the calmodulin inhibitory peptide. Our results indicated that trifluoperazine blocks hNav1.5 current in concentration-, state- and use dependent manners rather than via calmodulin inhibition. PMID- 27666480 TI - Alpha-synuclein activates BV2 microglia dependent on its aggregation state. AB - Synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are defined by the presence of intracellular alpha-synuclein aggregates in neurons and/or oligodendrocytes. In addition, post mortem tissue analysis revealed profound changes in microglial morphology, indicating microglial activation and neuroinflammation. Thus, alpha synuclein may directly activate microglia, leading to increased production of key pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), which in turn modulates the disease progression. The distinct alpha-synuclein species, which mediates the activation of microglia, is not well defined. We hypothesized that microglial activation depends on a specific aggregation state of alpha-synuclein. Here, we show that primarily human fibrillar alpha-synuclein increased the production and secretion of pro inflammatory cytokines by microglial BV2 cells compared to monomeric and oligomeric alpha-synuclein. BV2 cells also preferentially phagocytosed fibrillar alpha-synuclein compared to alpha-synuclein monomers and oligomers. Microglial uptake of alpha-synuclein fibrils and the consequent activation were time- and concentration-dependent. Moreover, the degree of fibrillization determined the efficiency of microglial internalization. Taken together, our study highlights the specific crosstalk of distinct alpha-synuclein species with microglial cells. PMID- 27666481 TI - Phosphatidylinositol (3,4,5)-trisphosphate binds to sortilin and competes with neurotensin: Implications for very low density lipoprotein binding. AB - Sortilin is a multi-ligand sorting receptor that interacts with B100-containing VLDL and LDL as well as other ligands including neurotensin (NT). The current study investigates the hypothesis that phosphatidylinositol (3,4,5)-trisphosphate (PIP3) generated downstream of insulin action can directly bind to sortilin. NT binds to sortilin at a well characterized site via its carboxy terminus (C-term). Using a crystal structure of human sortilin (hsortilin), PIP3 is predicted to bind at this C-term site. Binding of PIP3 to hsortilin is demonstrated using surface plasmon resonance (SPR) flowing PIP3 nanodiscs over immobilized hsortilin. Studies were performed using SPR where dibutanoyl PIP3 is shown to compete with NT for sortilin binding. Rat VLDL and LDL were evaluated for PIP3 content immunologically using monoclonal antibodies directed against PIP3. Rat plasma VLDL contained three times more immunoreactive PIP3 than LDL per MUg of protein. Because VLDL contains additional ligands that bind sortilin, to distinguish specific PIP3 binding, we used PIP3 liposomes. Liposome floatation assays were used to demonstrate PIP3 liposome binding to sortilin. Using SPR and immobilized hsortilin, the C-term NT tetrapeptide (P-Y-I-L) is shown to bind to hsortilin. A compound (cpd984) was identified with strong theoretical binding to the site on sortilin involved in NT N-terminal binding. When cpd984 is co incubated with the tetrapeptide, the affinity of binding to sortilin is increased. Similarly, the affinity of PIP3 liposome binding increased in the presence of cpd984. Overall, results demonstrate that sortilin is a PIP3 binding protein with binding likely to occur at the C-term NT binding site. The presence of multiple ligands on B100-containing lipoproteins, VLDL and LDL, raises the interesting possibility for increased interaction with sortilin based on the presence of PIP3. PMID- 27666482 TI - Gene expression profiling of brain samples from patients with Lewy body dementia. AB - Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative disorder in the elderly. The development and progression of DLB remain unclear. In this study we used next generation sequencing to assess RNA expression profiles and cellular processes associated with DLB in the anterior cingulate cortex, a brain region affected by DLB pathology. The expression measurements were made in autopsy brain tissues from 8 DLB subjects and 10 age-matched controls using AmpliSeq technology with ion torrent sequencing. The analysis of RNA expression profiles revealed 490 differentially expressed genes, among which 367 genes were down-regulated and 123 were up-regulated. Functional enrichment analysis of genes differentially expressed in DLB indicated downregulation of genes associated with myelination, neurogenesis, and regulation of nervous system development. miRNA binding sites enriched in these mRNAs yielded a list of candidate miRNAs participating in DLB pathophysiology. Our study provides a comprehensive picture of gene expression landscape in DLB, identifying key cellular processes associated with DLB pathology. PMID- 27666483 TI - Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease. AB - Recently, hydropersulfide (RSSH) was found to exist in mammalian tissues and fluids. Cysteine hydropersulfide can be found in free cysteine residues as well as in proteins, and it has potent antioxidative activity. Human serum albumin (HSA) is the most abundant protein in mammalian serum. HSA possesses a free thiol group in Cys-34 that could be a site for hydropersulfide formation. HSA hydropersulfide of high purity as a positive control was prepared by treatment of HSA with Na2S. The presence of HSA hydropersulfide was confirmed by spectroscopy and ESI-TOFMS analysis where molecular weights of HSA hydropersulfide by increments of approximately 32 Da (Sulfur atom) were detected. The fluorescent probe results showed that Alexa Fluor 680 conjugated maleimide (Red-Mal) was a suitable assay and bromotrimethylammoniumbimane bromide appeared to be a selective reagent for hydropersulfide. The effect of oxidative stress related disease on the existence of albumin hydropersulfides was examined in rat 5/6 nephrectomy model of chronic kidney disease (CKD). Interestingly, the level of hydropersulfides in rat 5/6 nephrectomy model serum was decreased by a uremic toxin that increases oxidative stress in rat 5/6 nephrectomy model. Furthermore, we demonstrated that the levels of HSA hydropersulfide in human subjects were reduced in CKD but restored by hemodialysis using Red-Mal assay. We conclude that HSA hydropersulfide could potentially play an important role in biological anti oxidative defense, and it is a promising diagnostic and therapeutic marker of oxidative diseases. PMID- 27666484 TI - Combined SRC inhibitor saracatinib and anti-ErbB2 antibody H2-18 produces a synergistic antitumor effect on trastuzumab-resistant breast cancer. AB - Despite of the effectiveness of the anti-ErbB2 humanized antibody trastuzumab, trastuzumab resistance emerges as a major and common clinical problem. Thus, circumventing trastuzumab resistance has become an urgent need. Recently, Src inhibitor saracatinib has drawn great attention for its key role in trastuzumab response. As shown in our previous study, H2-18, an anti-ErbB2 antibody, could potently induce programmed cell death (PCD) in trastuzumab-resistant breast cancer cells. Here we combined H2-18 and a Src inhibitor, saracatinib, and studied the antitumor activity of this drug combination in trastuzumab-resistant breast cancer cell lines. The results showed that H2-18 and saracatinib could synergistically inhibit cell proliferation of BT-474, SKBR-3, HCC-1954 and HCC 1419 breast cancer cell lines in vitro. H2-18 plus saracatinib could also inhibit the HCC-1954 tumor growth more effectively in vivo than each drug alone. H2-18 plus saracatinib showed a significantly more potent PCD-inducing activity compared with either H2-18 or saracatinib alone. We conclude that enhanced PCD may contribute to the superior antitumor efficacy of this combination therapy. The combination of H2-18 and SRC inhibitor has the potential to be translated into clinic. PMID- 27666485 TI - Thunbergia alata inhibits inflammatory responses through the inactivation of ERK and STAT3 in macrophages. AB - Thunbergia alata (Acanthaceae) has been used traditionally to treat various inflammatory diseases such as fever, cough and diarrhea in East African countries including Uganda and Kenya. However, systemic studies elucidating the anti inflammatory effects and precise mechanisms of action of T. alata have not been conducted, to the best of our knowledge. To address these concerns, we explored the anti-inflammatory effects of a methanol extract of T. alata (MTA) in macrophages. Non-cytotoxic concentrations of MTA (<=300 ug/ml) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by transcriptional regulation of inducible NO synthase in a dose dependent manner. The expression of cyclooxygenase-2, the enzyme responsible for the production of prostaglandin E2, was unchanged by MTA at the mRNA and protein levels. MTA treatment inhibited interleukin (IL)-6 production and decreased the mRNA expression of pro-inflammatory cytokines, including IL-6 and IL-1beta. Tumor necrosis factor-alpha production and mRNA expression were not regulated by MTA treatment. The decreased production of inflammatory mediators by MTA was followed by the reduced phosphorylation of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3). MTA treatment had no effect on activity of other mitogen-activated protein kinases (MAPKs), p38, c-Jun N-terminal kinase (JNK), and nuclear factor-kappaB (NF-kappaB). These results indicate that MTA selectively inhibits the excessive production of inflammatory mediators in LPS-stimulated murine macrophages by reducing the activity of ERK and STAT3, suggesting that MTA plays an important inhibitory role in the modulation of severe inflammation. PMID- 27666486 TI - Agkihpin, a novel SVTLE from Gloydius halys Pallas, promotes platelet aggregation in vitro and inhibits thrombus formation in vivo in murine models of thrombosis. AB - In previous work, a snake venom arginine esterase (SVAE), agkihpin from the venom of Gloydius halys Pallas, was isolated and its biochemical data including Mr, PI, amino acid components and sugar content was collected. Here, the agkihpin was cloned and further characterized and we found that agkihpin could promote ADP induced platelets aggregation, hydrolyze fibrin, cleave Aalpha and Bbeta chains of fibrinogen and reduce the thrombosis induced by thrombin. Moreover, agkihpin hydrolyzed TAME with optimum temperatures at 30 degrees C-45 degrees C, and the hydrolysis was inhibited by EDTA, PMSF, DTT and promoted by Ca2+, Fe3+, Mg2+, Zn2+. The sequence features of agkihpin were detected as follows: the N-terminal residues was determined as I(V)L(Y)GDDECNINE by protein sequencing; the ORF was determined as 705 bp, and the deduced amino acid sequence was identified by peptide mass fingerprinting; the cysteines, cleavage sites, active sites and substrate binding sites of snake venom thrombin-like enzyme (SVTLE), were all conserved in amino acid sequence of agkihpin; 2 Leu(Tyr), 4 Asn and 121 Ile in amino acid sequence of agkihpin were first found in the amino acid sequences of SVTLEs. These findings indicated that agkihpin is a novel SVTLE. What's more, due to its several advantages of fibrino(gen)olytic and thrombosis-reduced activities, and devoid of bleeding risk, agkihpin may be developed into a thrombolytic drug in the future. PMID- 27666487 TI - Adherence to infection prevention and control guidelines: A vignette-based study of decision-making and risk-taking in young adults with cystic fibrosis. AB - BACKGROUND: Balancing cystic fibrosis (CF) care with demands of normal life is associated with decreased adherence to infection prevention and control (IPC) guidelines. METHODS: Adults with CF, aged 18-25years, were invited to participate via UK CF Trust social media platforms. An online survey evaluated participants' decision-making in nine clinician-rated vignettes and assessed the perceived influence of infection-related information sources. RESULTS: Participants (n=87, mean 21.4years [SD=2.45]; 75% female) were less likely to engage in the high-risk scenarios, although demonstrated greater awareness of cross-infection than environmental risks. Associations between risk-perception and willingness to participate in five vignette-based hypothetical activities were significant (p<0.05). Thematic analysis emphasised influences of past experience and a need to achieve good quality of life. Knowledge gaps were evident. CONCLUSIONS: People with CF make decisions that discriminate between risk-levels but are not always based on robust knowledge. They also show some inclination towards engaging in risky behaviours. PMID- 27666488 TI - MicroRNAs modulate the expression of the SOX18 transcript in lung squamous cell carcinoma. AB - Recent statistics show that lung cancer is the second most common malignant tumor in the world (14% of all cancers in the USA), both in terms of morbidity and mortality. The mortality of this type of tumor shows an increasing trend (28% for men and 26% for women). Lung squamous cell carcinoma (LSCC) is the second-largest histological subtype of non-small cell lung cancers (NSCLCs) after adenocarcinoma. SRY-related HMG-box 18 (SOX18) protein is an important transcription factor involved in the development of the cardiovascular system and the lymphatic ducts. In addition, it was observed that SOX18 functions in wound healing processes and the development of atherosclerosis. Likewise, an increased level of this protein was found in melanomas and malignant pancreatic, stomach and breast tumors. Furthermore, high expression of SOX18 in gastric cancer stromal cells was found to be associated with a poor patient prognosis. In the present study, we analyzed the expression of the SOX18 protein and the mRNA level in postoperative samples of LSCC and non-malignant lung tissues (NMLTs), and a disparity in both levels was observed. Because of the fact that microRNAs (miRNAs) play important roles in the initiation and progression of lung cancer, the main aim of this study was to identify the miRNAs that interact with the SOX18 transcript in NSCLC cases. SOX18 mRNA expression level was significantly lower in the LSCC tissues than that noted in the NMLTs (p<0.01). However, protein levels were higher in the LSCC cases compared to these levels in the NMLTs (p<0.0001). We showed that miR-7a and miR-24-3p were expressed more highly in the NMLTs than levels in the LSCC samples, and that they could be switched off in lung cancer tissue. Additionally, correlations between RQ-values of SOX18 in NMLTs and LSCC samples (r=0.43, p=0.019), and between miR-7a and miR24-3p in NMLT cases (r=0.4, p=0.057) as well as in the LSCC samples (r=0.51, p=0.012) were noted. In conclusion, miRNAs interact with the mRNA of the SOX18 gene, but the mechanism by which they could be inhibited in cancer cells requires further examination. PMID- 27666489 TI - The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity. AB - Failure to maintain a normal in vivo erythrocyte half-life results in the development of hemolytic anemia. Half-life is affected by numerous factors, including energy balance, electrolyte gradients, reactive oxygen species, and membrane plasticity. The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a critical regulator of cellular energy balance. Previous roles for the alpha 1 and gamma 1 subunits in the control of erythrocyte survival have been reported. In the work described here, we studied the role of the beta 1 subunit in erythrocytes and observed microcytic anemia with compensatory extramedullary hematopoiesis together with splenomegaly and increased osmotic resistance. PMID- 27666490 TI - NOX-driven ROS formation in cell transformation of FLT3-ITD-positive AML. AB - In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation, including the promotion of leukemic cell proliferation and migration, as well as DNA damage and accumulation of mutations. Work reviewed in this article has revealed the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FMS-like tyrosine kinase 3 with internal tandem duplications (FLT3-ITD), an important oncoprotein in a subset of acute myeloid leukemias, causes activation of AKT and, subsequently, stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation, and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restores DEP-1 activity and attenuates cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy. PMID- 27666491 TI - Quality Improvement of Nasal Continuous Positive Airway Pressure Therapy in Neonatal Intensive Care Unit. AB - BACKGROUND: Nasal continuous positive airway pressure (NCPAP) therapy is widely used in neonates, but the clinical practice varies. However, nursing practice differs among individuals, and an inappropriate application method may delay the respiratory therapy, influence the beneficial effect of NCPAP, and increase complications. We introduced a quality improvement project to expedite the application of NCPAP therapy and decrease the incidence of nasal trauma. METHODS: A new strategy of mobile NCPAP cart with prepacked fixation kits and a written protocol was implemented from April 2006. All medical staff answered a questionnaire to assess their basic knowledge before and after intensive training. The records of the patients who were treated with NCPAP from October 2005 to November 2006 were reviewed. RESULTS: Fifty-nine medical staff were involved in the project, and their mean score for the questionnaire improved from 69.2 points to 98.3 points after training. From October 2005 to November 2006, 113 infants were recruited in total and 82 of them were admitted after the protocol was implemented. The NCPAP cart dramatically shortened the preparation time (from 520 seconds to 72 seconds) and the application time (from 468 seconds to 200 seconds). The use of the nursing protocol significantly decreased the incidence of nasal trauma in the study population (45.2% vs. 19.6%, p = 0.006), but not in infants with a birth weight of < 1000 g. Risk factors for nasal skin trauma included lower gestational age and birth weight, longer duration of NCPAP use, and lack of standardized nursing care. CONCLUSION: The mobile NCPAP cart with prepacked fixation kits is a practical way of expediting the initiation of NCPAP therapy. The written nursing protocol decreased the incidence of nasal trauma in infants, except for those with an extremely low birth weight. PMID- 27666492 TI - Has the Time Come for All to Routinely Use Intracameral Antibiotic Prophylaxis at the Time of Cataract Surgery? PMID- 27666493 TI - Creation of a 3-dimensional virtual dental patient for computer-guided surgery and CAD-CAM interim complete removable and fixed dental prostheses: A clinical report. AB - This clinical report proposes a digital workflow using 2-dimensional (2D) digital photographs, a 3D extraoral facial scan, and cone beam computed tomography (CBCT) volumetric data to create a 3D virtual patient with craniofacial hard tissue, remaining dentition (including surrounding intraoral soft tissue), and the realistic appearance of facial soft tissue at an exaggerated smile under static conditions. The 3D virtual patient was used to assist the virtual diagnostic tooth arrangement process, providing patient with a pleasing preoperative virtual smile design that harmonized with facial features. The 3D virtual patient was also used to gain patient's pretreatment approval (as a communication tool), design a prosthetically driven surgical plan for computer-guided implant surgery, and fabricate the computer-aided design and computer-aided manufacturing (CAD CAM) interim prostheses. PMID- 27666494 TI - Influence of aging on flexural strength of translucent zirconia for monolithic restorations. AB - STATEMENT OF PROBLEM: Concern has been raised with regard to the low-temperature degradation (LTD) of translucent yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP) for monolithic zirconia restorations. PURPOSE: The purpose of this in vitro study was to assess the LTD behavior of 4 commercially available translucent Y-TZP materials by accelerated aging specimens in steam at 134 degrees C, 0.2 MPa. MATERIAL AND METHODS: Thin bars (22*3*0.2 mm) of Y-TZP, including Katana ML (Kuraray Noritake Dental Inc), Katana HT13 (Kuraray Noritake Dental Inc), Prettau (Zirkonzahn), and BruxZir (Glidewell Laboratories) (n=30 for each group), were machined from sintered blocks. Control specimens were assessed in the nonaged condition. Artificially ageing (n=5 per group at 5, 50, 100, 150, and 200 hours) was conducted in steam at 134 degrees C at 0.2 MPa. The specimens were characterized, tested in 4-point flexure, and the fracture surfaces were analyzed. The monoclinic-to-tetragonal (m/t) peak intensity ratio measured by x ray diffraction was used to calculate the monoclinic phase fraction and monitor LTD. Linear regression with heteroscedasticity-consistent robust standard errors was used to test for the effect of LTD (aging time) on (sigmaf) and m/t. The Spearman rank correlation coefficient was used to assess the relationship between sigmaf and monoclinic phase fraction (alpha=.05). RESULTS: Artificial aging resulted in LTD as shown by an increase in the monoclinic phase fraction for all specimens. After aging for 200 hours, the mean +/-SD monoclinic phase fraction increased from 2.90 +/-0.34% to 76.1 +/-0.64% for Prettau, 2.69 +/-0.18% to 76.0 +/-0.26% for BruxZir, 4.6 +/-0.19% to 35.8 +/-0.80% for Katana HT13, and 3.57 +/ 0.35% to 33.2 +/-1.1% for Katana ML (all P<.001). Flexural strength changed from a mean +/-SD of 1612 +/-197 MPa to all fractured during aging for Prettau (P<.001); 1248 +/-73.5 MPa to all fractured during aging for BruxZir (P<.001); 1052 +/-84.2 to 1099 +/-70 MPa +/-130 for Katana HT13 (P=.45); and from 875 +/ 130 to 909 +/-70 MPa (P=.82) for Katana ML. The mean flexural strength values of Prettau and BruxZir decreased with an increase in the monoclinic phase with Spearman rank correlation coefficients of -0.80 (P=.001) for Prettau and -0.63 (P=.022) for BruxZir. No significant changes in flexural strength were measured for Katana ML or Katana HT13 (P>.05). CONCLUSIONS: The LTD of Y-TZP resulted in a significant decrease in flexural strength of Prettau and BruxZir, whereas Katana ML and Katana HT13 exhibited less LTD and no significant decrease in flexural strength. PMID- 27666495 TI - Implant-supported and magnet-retained oral-nasal combination prosthesis in a patient with a total rhinectomy and partial maxillectomy due to cancer: A clinical report. AB - This clinical report describes the fabrication of an implant-supported and magnet retained combination oral-nasal prosthesis for a patient with a midline midfacial defect. The patient had undergone a total rhinectomy and partial maxillectomy as part of his cancer treatment. The nasal prosthesis was retained on the face by a magnet attached to the implant-supported maxillary denture, resulting in improved appearance and the recovery of speech, mastication, and swallowing functions. PMID- 27666497 TI - Marginal fit and photoelastic stress analysis of CAD-CAM and overcast 3-unit implant-supported frameworks. AB - STATEMENT OF PROBLEM: Several studies have shown the superiority of computer assisted design and computer-assisted manufacturing (CAD-CAM) technology compared with conventional casting. However, an advanced technology exists for casting procedures (the overcasting technique), which may serve as an acceptable and affordable alternative to CAD-CAM technology for fabricating 3-unit implant supported fixed dental prostheses (FDPs). PURPOSE: The purpose of this in vitro study was to evaluate, using quantitative photoelastic analysis, the effect of the prosthetic framework fabrication method (CAD-CAM and overcasting) on the marginal fit and stress transmitted to implants. The correlation between marginal fit and stress was also investigated. MATERIAL AND METHODS: Three-unit implant supported FDP frameworks were made using the CAD-CAM (n=10) and overcasting (n=10) methods. The frameworks were waxed to simulate a mandibular first premolar (PM region) to first molar (M region) FDP using overcast mini-abutment cylinders. The wax patterns were overcast (overcast experimental group) or scanned to obtain the frameworks (CAD-CAM control group). All frameworks were fabricated from cobalt-chromium (CoCr) alloy. The marginal fit was analyzed according to the single-screw test protocol, obtaining an average value for each region (M and PM) and each framework. The frameworks were tightened for the photoelastic model with standardized 10-Ncm torque. Stress was measured by quantitative photoelastic analysis. The results were submitted to the Student t test, 2-way ANOVA, and Pearson correlation test (alpha=.05). RESULTS: The framework fabrication method (FM) and evaluation site (ES; M and PM regions) did not affect the marginal fit values (P=.559 for FM and P=.065 for ES) and stress (P=.685 for FM and P=.468 for ES) in the implant-supported system. Positive correlations between marginal fit and stress were observed (CAD-CAM: r=0.922; P<.001; overcast: r=0.908; P<.001). CONCLUSIONS: CAD-CAM and overcasting methods present similar marginal fit and stress values for 3-unit FDP frameworks. The decreased marginal fit of frameworks induces greater stress in the implant-supported system. PMID- 27666496 TI - A systematic comparison of bar-clips versus magnets. AB - STATEMENT OF PROBLEM: Currently, which type of suprastructure is preferred when fabricating implant-retained craniofacial prostheses is unknown. PURPOSE: The purpose of this systematic review was to identify the best retention system (bar clips versus magnets) for implant-retained craniofacial prostheses. MATERIAL AND METHODS: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A systematic search of Medline/PubMed and Web of Science databases for clinical trials was conducted on implant-retained craniofacial prostheses published between 2005 and 2015. English-language studies that directly compared different types of retention systems or presented information on implant survival, periimplant soft tissue reactions, and prosthetic complications were included. Nonclinical studies were excluded to eliminate bias. RESULTS: A total to 173 studies were identified, of which 10 satisfied the inclusion criteria. In total, 492 participants were included in these studies. Four selected studies displayed detailed information with regard to the number of implant failures according to the retention system. As reported, 29 (18.2%) of 159 implants with magnets failed, whereas 25 (31.6%) of 79 implants with bars failed. Overall auricular superstructures showed the highest survival (99.08%). In addition, 55.4% of all participants in the selected studies showed grade 0 of periimplant soft tissue reactions. CONCLUSIONS: A systematic search for clinical studies resulted in few studies with a short-term follow-up and small number of participants. The limited data collected indicated that magnets show fewer complications than bar superstructures; however, no hard conclusions could be drawn. Further research, preferably in the form of clinical trials, is needed to validate these findings. PMID- 27666498 TI - Selected physical properties of new resin-modified glass ionomer luting cements. AB - STATEMENT OF PROBLEM: Two resin-modified glass ionomer (RMGI)-based luting agents have been recently marketed without independent reports of their physical properties. PURPOSE: The purpose of this in vitro study was to evaluate selected physical properties of 2 newly marketed RMGI luting agents and compare the findings with traditional materials. MATERIAL AND METHODS: Specimens (N=12) of Nexus RMGI, UltraCem, GC Fuji Cem 2, and RelyX Luting Plus were fabricated using standardized molds for flexural strength and fracture toughness according to manufacturer recommendations and stored in physiologic phosphate-buffered saline solution at 37 degrees C until testing. Specimens were tested at 1 and 24 hours, 1 week, and 1 month. Mean values for flexural strength, flexural modulus, flexural toughness, and fracture toughness were determined. Additionally, film thickness (N=12) for each material was determined following Amerian National Standards Association/American Dental Association (ANSI/ADA) specifications. Mean results were analyzed with Kruskal-Wallis and Mann-Whitney U tests (alpha=.05). RESULTS: All luting agents exhibited a similar film thickness that met ANSI/ADA requirements for aqueous-based luting agents. Nexus RMGI surprisingly demonstrated significantly greater flexural strength and fracture toughness at 1 hour, which decreased significantly at 24 hours, making it similar to the other materials evaluated. All materials had similar flexural strength values at 7 days. CONCLUSIONS: Physical property performance was material dependent. Nexus RMGI demonstrated greater early physical properties that were significantly less at 24 hours. UltraCem, GC Fuji Cem 2, and RelyX Luting Plus demonstrated the increasing physical property development that is normally associated with polyalkenoate-based systems. PMID- 27666499 TI - Colorimetric distribution of human attached gingiva and alveolar mucosa. AB - STATEMENT OF PROBLEM: Few studies have investigated the colorimetric distribution of gingival color, including the posterior area and alveolar mucosa. PURPOSE: The purpose of this in vivo study was to investigate the distribution of colorimetric values in different areas of gingiva and to determine its relationship to colorimetric findings of the tooth and skin in a young Korean population. MATERIAL AND METHODS: Participants included 40 periodontally healthy adults (22 men and 18 women) 25 to 36 years of age. Commission Internationale de l'Eclairage values (CIELab: L* lightness, a* green-red, and b* blue-yellow) were measured using a colorimeter at a total of 23 sites for each participant, including attached gingiva (AG) and alveolar mucosa (AM) in the maxillary and mandibular and incisor and molar regions, maxillary central incisor, and skin points of the glabella, cheek, and inner upper arm. RESULTS: AG showed higher L* and lower a* values than AM. AG demonstrated higher L* and lower a* values in the maxillary region than in the mandibular region and higher b* values in the incisor region than in the molar region. AM revealed higher L* and lower a* and b* values in the incisor region than in the molar region. Positive significant correlations were found for L* between the skin area and AM and for b* between the skin area and AG. CONCLUSIONS: The colorimetric values of AG and AM differ according to the area, possibly as a result of differences in anatomic and histologic distribution that influence optical properties. PMID- 27666500 TI - Accuracy of single-abutment digital cast obtained using intraoral and cast scanners. AB - STATEMENT OF PROBLEM: Scanners are frequently used in the fabrication of dental prostheses. However, the accuracy of these scanners is variable, and little information is available. PURPOSE: The purpose of this in vitro study was to compare the accuracy of cast scanners with that of intraoral scanners by using different image impression techniques. MATERIAL AND METHODS: A poly(methyl methacrylate) master model was fabricated to replicate a maxillary first molar single-abutment tooth model. The master model was scanned with an accurate engineering scanner to obtain a true value (n=1) and with 2 intraoral scanners (CEREC Bluecam and CEREC Omnicam; n=6 each). The cast scanner scanned the master model and duplicated the dental stone cast from the master model (n=6). The trueness and precision of the data were measured using a 3-dimensional analysis program. The Kruskal-Wallis test was used to compare the different sets of scanning data, followed by a post hoc Mann-Whitney U test with a significance level modified by Bonferroni correction (alpha/6=.0083). The type 1 error level (alpha) was set at .05. RESULTS: The trueness value (root mean square: mean +/ standard deviation) was 17.5 +/-1.8 MUm for the Bluecam, 13.8 +/-1.4 MUm for the Omnicam, 17.4 +/-1.7 MUm for cast scanner 1, and 12.3 +/-0.1 MUm for cast scanner 2. The differences between the Bluecam and the cast scanner 1 and between the Omnicam and the cast scanner 2 were not statistically significant (P>.0083), but a statistically significant difference was found between all the other pairs (P<.0083). The precision of the scanners was 12.7 +/-2.6 MUm for the Bluecam, 12.5 +/-3.7 MUm for the Omnicam, 9.2 +/-1.2 MUm for cast scanner 1, and 6.9 +/ 2.6 MUm for cast scanner 2. The differences between Bluecam and Omnicam and between Omnicam and cast scanner 1 were not statistically significant (P>.0083), but there was a statistically significant difference between all the other pairs (P<.0083). CONCLUSIONS: An Omnicam in video image impression had better trueness than a cast scanner but with a similar level of precision. PMID- 27666501 TI - Authors' response: efficacy and safety of pelvic packing after emergency peripartum hysterectomy (EPH) in postpartum hemorrhage (PPH) setting. PMID- 27666502 TI - WANTED - Dead or alive: Myotubularins, a large disease-associated protein family. AB - Myotubularins define a large family of proteins conserved through evolution. Several members are mutated in different neuromuscular diseases including centronuclear myopathies and Charcot-Marie-Tooth (CMT) neuropathies, or are linked to a predisposition to obesity and cancer. While some members have phosphatase activity against the 3-phosphate of phosphoinositides, regulating the phosphorylation status of PtdIns3P and PtdIns(3,5)P2 implicated in membrane trafficking and autophagy, and producing PtdIns5P, others lack key residues in the catalytic site and are classified as dead-phosphatases. However, these dead phosphatases regulate phosphoinositide-dependent cellular pathways by binding to catalytically active myotubularins. Here we review previous studies on the molecular regulation and physiological roles of myotubularins. We also used the recent myotubularins three-dimensional structures to underline key residues that are mutated in neuromuscular diseases and required for enzymatic activity. In addition, through database mining and analysis, expression profile and specific isoforms of the different myotubularins are described in depth, as well as a revisited protein interaction network. Comparison of the interactome and expression data for each myotubularin highlights specific protein complexes and tissues where myotubularins should have a key regulatory role. PMID- 27666504 TI - Creating Opportunities for Optimal Nutritional Experiences for Infants With Complex Congenital Heart Disease. AB - INTRODUCTION: To our knowledge, successful breastfeeding in the population with single ventricle congenital heart disease has not been reported in the literature, particularly during the interstage period. METHOD: A retrospective case study including inpatient nutrition and a complete history of daily logs with the home surveillance monitoring program was performed. RESULTS: Successful full breastfeeding (exceeding prescribed weight growth goals) after Stage I surgery was achieved during the interstage period. The infant was discharged at 3.41 kg, not consistently breastfeeding, and progressed to 7.05 kg at 5 months of age, fully breastfeeding. CONCLUSION: Supporting breastfeeding for infants who have undergone repairs for single ventricle anatomy can be challenging but can be accomplished. It requires a concerted team effort, clear communication, and collaboration among caregivers, the mother, and her supporters. PMID- 27666505 TI - Opioid Addiction in Adolescents: A Background and Policy Brief. PMID- 27666506 TI - Inhibition of autophagy sensitises cells to hydrogen peroxide-induced apoptosis: Protective effect of mild thermotolerance acquired at 40 degrees C. AB - Various toxic compounds produce reactive oxygen species, resulting in oxidative stress that threatens cellular homeostasis. Yet, lower doses of stress can stimulate defence systems allowing cell survival, whereas intense stress activates cell death pathways such as apoptosis. Mild thermal stress (40 degrees C, 3h) induces thermotolerance, an adaptive survival response that renders cells less sensitive to subsequent toxic stress, by activating defence systems like heat shock proteins, antioxidants, anti-apoptotic and ER-stress factors. This study aims to understand how autophagy and apoptosis are regulated in response to different doses of H2O2, and whether mild thermotolerance can protect cervical carcinoma cells against apoptosis by stimulating autophagy. Autophagy was monitored through Beclin-1 and LC3 expression and acid compartment activity, whereas apoptosis was tracked by caspase activity and chromatin condensation. Exposure of HeLa and C33 A cells to H2O2 for shorter times (15-30min) transiently induced autophagy; apoptosis was activated after longer times (1-3h). Mild thermotolerance at 40 degrees C enhanced activation of autophagy by H2O2. Disruption of autophagy using bafilomycin A1 and 3-methyladenine sensitised cells to apoptosis induced by H2O2, in non-thermotolerant cells and, to a lesser extent, in thermotolerant cells. Inhibition of autophagy enhanced apoptosis through the mitochondrial, death receptor and endoplasmic reticulum pathways. Autophagy was activated by lower doses of stress and protects cells against apoptosis induced by higher doses of H2O2. This work improves understanding of mechanisms that might be involved in toxicity of various compounds and could eventually lead to protective strategies against deleterious effects of toxic compounds. PMID- 27666503 TI - Regulation of cellular proliferation in acute lymphoblastic leukemia by Casein Kinase II (CK2) and Ikaros. AB - The IKZF1 gene encodes the Ikaros protein, a zinc finger transcriptional factor that acts as a master regulator of hematopoiesis and a tumor suppressor in leukemia. Impaired activity of Ikaros is associated with the development of high risk acute lymphoblastic leukemia (ALL) with a poor prognosis. The molecular mechanisms that regulate Ikaros' function as a tumor suppressor and regulator of cellular proliferation are not well understood. We demonstrated that Ikaros is a substrate for Casein Kinase II (CK2), an oncogenic kinase that is overexpressed in ALL. Phosphorylation of Ikaros by CK2 impairs Ikaros' DNA-binding ability, as well as Ikaros' ability to regulate gene expression and function as a tumor suppressor in leukemia. Targeting CK2 with specific inhibitors restores Ikaros' function as a transcriptional regulator and tumor suppressor resulting in a therapeutic, anti-leukemia effect in a preclinical model of ALL. Here, we review the genes and pathways that are regulated by Ikaros and the molecular mechanisms through which Ikaros and CK2 regulate cellular proliferation in leukemia. PMID- 27666507 TI - Antimicrobial susceptibility of microorganisms isolated from sputum culture of patients with cystic fibrosis: Methicillin-resistant Staphylococcus aureus as a serious concern. AB - INTRODUCTION: Infection is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Antimicrobial resistance of the bacterial spp. particularly methicillin resistance in Staphylococcus aureus has caused a lot of attention. The aim of this study was to describe the prevalence of S. aureus, Pseudomonas aeruginosa and Burkholderia cepacia-complex as well as their antimicrobial susceptibility patterns in CF patients in an Iranian referral pediatrics Hospital. MATERIAL AND METHODS: From March 2011 until February 2012, 172 samples were collected at the Children Medical Center (CMC), an Iranian referral hospital in Tehran, Iran. Sputum specimens were cultured for the following bacterial pathogens: P. aeruginosa, S. aureus, B. cepacia complex. Antimicrobial susceptibility was performed according to the Clinical Laboratory Standards Institute recommendations. RESULTS: In our study, 54% of the patients (n = 93) harbored at least once S. aureus, 30% (n = 52) P. aeruginosa, and 2% (n = 3) Burkholderia cepacia. In 40 patients (23%), none of these organisms was grown. An increasing colonization rate of P. aeruginosa in the second decade of life was found. In contrast, the colonization rate of S. aureus was constant in both decades of life. Methicillin resistant S. aureus (MRSA) was detected in 40 isolates (43%). Among MRSA, no resistance against vancomycin, linezolid and quinupristin/dalfopristin occurred. The susceptibility of P. aeruginosa isolates to meropenem, imipenem, doripenem, levofloxacin and polymixin B were more than 90%. CONCLUSION: The prevalence of MRSA has been rising. Since its impact on clinical outcomes, optimal prevention and treatment strategies are unclear, further studies to expand the knowledge about the infection control strategies and MRSA treatment are highly recommended. PMID- 27666508 TI - Ferric hydroxamate uptake system contributes to Edwardsiella ictaluri virulence. AB - Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia in fish, particularly in channel catfish. Ferric iron is an essential micronutrient for bacterial survival, and some bacterial pathogens use secreted hydroxamate-type siderophores to chelate iron in host tissues. Siderophore-iron complexes are taken up by these bacteria via the ferric hydroxamate uptake (Fhu) system. In E. ictaluri, the Fhu system consists of fhuC, fhuD, fhuB, and fhuA genes. However, the importance of the Fhu system in E. ictaluri virulence has not been investigated completely. Here, we present construction of E. ictaluri fhuD and fhuB mutants (EiDeltafhuD and EiDeltafhuB) by in-frame gene deletion and evaluation of the mutants' virulence and immunogenicity in channel catfish fingerlings and fry. Immersion challenges showed that EiDeltafhuD was not significantly attenuated (p < 0.05) in catfish fingerlings, whereas EiDeltafhuB was significantly attenuated (p < 0.01). Catfish fingerlings immunized with EiDeltafhuD and EiDeltafhuB showed 100% and 97.62% survival, respectively. Fry immersion challenges indicated EiDeltafhuB was also significantly attenuated (p < 0.05) in two-week old fry compared to the wild-type (48.96% vs. 82.14% mortalities). The survival rate in the fry vaccinated with EiDeltafhuB was significantly higher (p < 0.05) than that of non-vaccinated fry (96.77% vs. 21.42% survival). Our data indicates that the fhuB gene, but not the fhuD gene, contributes to E. ictaluri virulence. PMID- 27666509 TI - A novel missense mutation in the NADPH binding domain of CYBB abolishes the NADPH oxidase activity in a male patient with increased susceptibility to infections. AB - Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the five structural genes (CYBB, CYBA, NCF1, NCF2, and NCF4) that typically results in a decrease in function or inability to generate a respiratory burst, leading to defective killing of pathogens, including fungi and intracellular bacteria. Mutations in CYBB, encoding the gp91phox (also known as NOX2) result in X-linked CGD account for approximately 65% of CGD cases. Here, we aimed the characterization of a novel missense mutation c.1226C > A/p.A409E in the CYBB gene in a patient with X-linked CGD. Relevant clinical data of a male patient whose family was positive for XCGD was reviewed. Oxidative burst and NADPH protein expression was evaluated by flow cytometry, while Genetic analysis was performed by Sanger sequencing. Monocyte-derived macrophages (MDMs) were evaluated for their capacity for phagocytosis and growth suppression of the intracellular Mycobacterium tuberculosis (M. tuberculosis). We thus report the absence of an oxidative burst in the phagocytes of the patient. Flow cytometry evaluation revealed a normal expression of NADPH oxidase components in neutrophils and genetic analysis proved the existence of a novel missense c.1226C > A mutation in the CYBB gene resulting in p.A409E. Further, we have showed that the patient's MDMs were unhindered in their ability to take up mycobacteria normally. Instead, the MDMs failed to control the intracellular proliferation of M. tuberculosis, a phenotype that improved in the presence of recombinant human interferon-gamma (rhIFN-gamma). This work expands the genetic spectrum of X linked CGD and demonstrates improvement in macrophage function in X91+CGD patient by rhIFN-gamma. PMID- 27666510 TI - Clinical relevance of Helicobacter pylori virulence factors in Iranian patients with gastrointestinal diseases. AB - Helicobacter pylori (H. pylori) usually colonizes the gastric mucosa of more than 50% of the human population, causing an infection that may appear in early childhood and can persist for life. H. pylori is suggested as the main cause of peptic ulcer and chronic gastritis. It is also associated with gastric cancer. Its severity and symptoms depend on environmental factors, host susceptibility and bacterial components, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori is genetically highly variable, and the variability which affects H. pylori virulence factors might be useful in identifying the strains with different degrees of pathogenicity. The geographic distribution of distinct H. pylori genotypes is largely unknown and should be established. The prevalence of more pathogenic genotypes in certain areas may have important epidemiological consequences. It also might be associated with the severity of H. pylori related diseases in such regions. Given that Iran is located in the Middle East and Asian populations have revealed high levels of gastric cancer, it is of clinical interest to clarify the potential of H. pylori virulence markers in predicting the associated clinical outcomes. In this review, clinical relevance of adhesion molecules and significant virulence factors of H. pylori in Iranian patients with gastrointestinal diseases are discussed in comparison to other countries. PMID- 27666511 TI - Clinical, cytological and microbiological evaluation of bronchoalveolar lavage in children: A referral hospital-based study. AB - INTRODUCTION: Diffuse lung diseases (DLD) in children involve a group of heterogeneous, rare disorders. In spite of the low diagnostic yield in pediatric DLD, bronchoalveolar lavage (BAL) can be used to diagnose specific disorders. There are few studies about microbial and cellular profiles of BAL samples in these patients. This study was conducted to evaluate the clinical, cytological and microbiological evaluation of BAL in children with DLD. METHODS: The clinical, cytological and microbiological profiles of BAL samples of all patients with DLD who underwent the fiberoptic bronchoscopy (FOB) at Children's Medical Center, an Iranian referral pediatrics Hospital during a year were evaluated. RESULTS: In 18 patients (18.4%) of the 98 cases studied, 22 pathogens were obtained as etiologic agents. The mean total cells count of BAL was 23.9 * 104 +/ 12.9 * 104/ml. The mean percentages of cellular components were macrophages (70.2%), neutrophils (16.3%), lymphocytes (11.8%) and eosinophils (1.4%), respectively. The type of lung disease was significantly associated with the mean percentage of lymphocytes (p = 0.005) and the percentage of neutrophils (p = 0.042). CONCLUSION: FOB and BAL evaluation in combination with clinical and radiographic imaging data may be helpful for identifying of presumptive diagnosis of DLD in children. PMID- 27666512 TI - Productivity costs of work loss associated with osteoarthritis in Canada from 2010 to 2031. AB - OBJECTIVE: To estimate and project the productivity costs of work loss (PCWL) associated with osteoarthritis (OA) in Canada using the Population Health Model (POHEM). DESIGN: We integrated an employment module based on 2006 Canadian Census into the previously developed microsimulation model of OA. The Canadian Community Health Survey (CCHS) Cycle 2.1 with an OA sample aged 25-64 (n = 7067) was used to calibrate the results of the employment module and to estimate the fraction of non-employment associated with OA. Probabilities of non-employment together with attributable fractions were then implemented in POHEM to estimate PCWL associated with OA from 2010 to 2031. RESULTS: Among the OA population, 44.4% and 59.4% of non-employment due to illness was associated with OA for those not working full year and part-year, respectively. According to POHEM projections, the size of the working age population with OA increased from 1.5 million in 2010 to 1.7 million in 2031. The PCWL associated with OA increased from $12 billion to $17.5 billion in constant 2008 Canadian dollars. Around 38% of this increase was due to the increase in OA prevalence and changes in demographics, while the rest was due to increase in real wage growth. Male and female OA patients between 55 and 64 years of age had the highest total projected PCWL, respectively. CONCLUSIONS: The total PCWL associated with OA in Canada is estimated to be substantial and increasing in future years. Results of this study could be used to inform policies aiming to increase employment sustainability among individuals with OA. PMID- 27666514 TI - True Randomness from Big Data. AB - Generating random bits is a difficult task, which is important for physical systems simulation, cryptography, and many applications that rely on high-quality random bits. Our contribution is to show how to generate provably random bits from uncertain events whose outcomes are routinely recorded in the form of massive data sets. These include scientific data sets, such as in astronomics, genomics, as well as data produced by individuals, such as internet search logs, sensor networks, and social network feeds. We view the generation of such data as the sampling process from a big source, which is a random variable of size at least a few gigabytes. Our view initiates the study of big sources in the randomness extraction literature. Previous approaches for big sources rely on statistical assumptions about the samples. We introduce a general method that provably extracts almost-uniform random bits from big sources and extensively validate it empirically on real data sets. The experimental findings indicate that our method is efficient enough to handle large enough sources, while previous extractor constructions are not efficient enough to be practical. Quality-wise, our method at least matches quantum randomness expanders and classical world empirical extractors as measured by standardized tests. PMID- 27666513 TI - Robotic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study. AB - STUDY OBJECTIVE: To assess the feasibility of total robotic radical surgery (TRRS) in patients with locally advanced cervical cancer (LACC) who receive chemoradiation therapy (CT/RT). DESIGN: A prospective (preplanned) study of a nonrandomized controlled trial (Canadian Task Force classification level 2). SETTING: Catholic University of the Sacred Hearth, Rome, Italy. PATIENTS: Between September 2013 and January 2016, a total of 40 patients with LACC (Federation Internationale de Gynecologie et d'Obstetrique stage IB2-III) were enrolled in the study. INTERVENTIONS: Robotic radical hysterectomy (RRH) plus pelvic and/or aortic lymphadenectomy was attempted within 6 weeks after CT/RT. The feasibility of TRRS as well as the rate, pattern, and severity of early and late postoperative complications were analyzed. MEASUREMENTS AND MAIN RESULTS: After CT/RT, 29 patients (72.5%) underwent type B2 RRH, and 11 (27.5%) underwent type C1 RRH. Pelvic lymphadenectomy was performed in all cases. TRRS was successful in 39 of 40 cases (feasibility rate = 97.5%). In patients successfully completing TRRS, the median operating time was 185 minutes (range, 100-330 minutes), and the median blood loss was 100 mL (range, 50-300 mL). The median time of hospitalization counted from the first postoperative day was 2 days (range, 1-4 days). No intraoperative complications were recorded. During the observation period (median = 18 months; range, 4-28 months), 9 of 40 (22.5%) experienced postoperative complications, for a total number of 12 complications. As of April 2016, recurrence of disease was documented in 5 cases (12.5%). CONCLUSION: TRRS is feasible in LACC patients administered preoperative CT/RT, providing perioperative outcomes comparable with those registered in early-stage disease, and LACC patients receiving neoadjuvant chemotherapy. PMID- 27666515 TI - Root Development and Endosymbioses: DELLAs Lead the Orchestra. AB - DELLA proteins, acting as integrators of gibberellin (GA) action, are emerging as key regulators of root system architecture. Recent studies have revealed how they dictate the dynamics of root growth and are required for the establishment of root endosymbioses with rhizobial bacteria and mycorrhizal fungi. Like conductors, DELLAs can thereby harmonize root development depending on soil environments. PMID- 27666516 TI - Transcriptional Regulatory Network of Plant Heat Stress Response. AB - Heat stress (HS) is becoming an increasingly significant problem for food security as global warming progresses. Recent studies have elucidated the complex transcriptional regulatory networks involved in HS. Here, we provide an overview of current knowledge regarding the transcriptional regulatory network and post translational regulation of the transcription factors involved in the HS response. Increasing evidence suggests that epigenetic regulation and small RNAs are important in heat-induced transcriptional responses and stress memory. It remains to be elucidated how plants sense and respond to HS. Several recent reports have discussed the heat sensing and signaling that activate transcriptional cascades; thus, we also highlight future directions of promoting crop tolerance to HS using these factors or other strategies for agricultural applications. PMID- 27666517 TI - ROS Are Good. AB - Reactive oxygen species (ROS) are thought to play a dual role in plant biology. They are required for many important signaling reactions, but are also toxic byproducts of aerobic metabolism. Recent studies revealed that ROS are necessary for the progression of several basic biological processes including cellular proliferation and differentiation. Moreover, cell death-that was previously thought to be the outcome of ROS directly killing cells by oxidation, in other words via oxidative stress-is now considered to be the result of ROS triggering a physiological or programmed pathway for cell death. This Opinion focuses on the possibility that ROS are beneficial to plants, supporting cellular proliferation, physiological function, and viability, and that maintaining a basal level of ROS in cells is essential for life. PMID- 27666518 TI - microRNAs involved in Parkinson's disease: A systematic review. AB - The aim of the present study was to determine the expression of blood microRNAs (miRNAs) involved in PD in humans. For this purpose the following electronic databases were selected: MEDLINE by Pubmed, Scopus and Web of Science. The search strategy included the proposed descriptors in the Medical Subject Headings. There were no restrictions with respect to the language of the publication. In the study selection two independent reviewers initially evaluated studies that were identified by the search strategy according to titles and abstracts. The reviewers evaluated (also unassisted) the complete articles and selected studies according to the eligibility criteria specified above. Studies that were not in accordance with the adopted criteria were excluded according to the boundaries imposed by the search strategy. The following data were extracted from the selected studies: Publication identification, location where the study was conducted, study design, the sample size, the participants' characteristics, the miRNAs involved in PD, the miRNA detection and analysis method, and the type of miRNA dysregulation in PD. Through this systematic review of the literature published over the last 10 years, the expression of 91 different miRNAs were analyzed in the context of PD, with the expression of 39 of these miRNAs differing significantly between individuals with PD and healthy controls and/or between treated and untreated patients with PD. The miRNAs were extracted from mononuclear cells, leukocytes, plasma, serum and peripheral blood, and the majority of the studies used reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is considered to be the gold standard for miRNA analysis. PMID- 27666520 TI - Role of phosphatase of regenerating liver 1 (PRL1) in spermatogenesis. AB - The PRL phosphatases are oncogenic when overexpressed but their in vivo biological function is less well understood. Previous gene deletion study revealed a role for PRL2 in spermatogenesis. We report here the first knockout mice lacking PRL1, the most related homolog of PRL2. We found that loss of PRL1 does not affect spermatogenesis and reproductive ability of male mice, likely due to functional compensation by the relatively higher expression of PRL2 in the testes. However, PRL1-/-/PRL2+/- male mice show testicular atrophy phenotype similar to PRL2-/- mice. More strikingly, deletion of one PRL1 allele in PRL2-/- male mice causes complete infertility. Mechanistically, the total level of PRL1 and PRL2 is negatively correlated with the PTEN protein level in the testis and PRL1+/-/PRL2-/- mice have the highest level of PTEN, leading to attenuated Akt activation and increased germ cell apoptosis, effectively halting spermatozoa production. These results provide the first evidence that in addition to PRL2, PRL1 is also required for spermatogenesis by downregulating PTEN and promoting Akt signaling. The ability of the PRLs to suppress PTEN expression underscores the biochemical basis for their oncogenic potential. PMID- 27666521 TI - Pro-adhesive phenotype of normal endothelial cells responding to metastatic breast cancer cell conditioned medium is linked to NFkappaB-mediated transcriptomic regulation. AB - Tumor microenvironment is an important promoter of tumorigenesis in all forms of breast cancer and has been associated with the risk of metastasis in the different breast cancer subtypes including the more frequent luminal subtypes that encompass 60% of cancer patients. Adhesive properties of endothelial cells (ECs) are strikingly affected during cancer cell dissemination and are related to functional changes of adhesion receptors. The contribution of tumor secreted factors to tumor-EC adhesion represents a therapeutic opportunity for breast cancer metastasis. Conditioned medium (CM) of tumor cells can be used as a model to study the role of the secreted molecules to the tumor microenvironment. We explored transcriptomic changes associated to a pro-adhesive phenotype in primary human umbilical vein endothelial cells (HUVECs) treated with CM of the breast cancer cell line ZR75.30 or with TNF for 3 h. Selected genes were used to validate the microarray through RT-qPCR. The bioinformatic analysis identified NFkappaB as the main regulator of the pro-adhesive phenotype and this was confirmed by pharmacological inhibition of NFkappaB pathway with BAY 11-7085. The changes induced by ZR75.30-CM mimic those promoted by TNF and display changes in the expression of genes related to inflammatory response, wound healing, extracellular matrix, cytokines, metabolism and cell communication. Despite the abundance of G-CSF, IL-8, IL-6 and VEGF in the ZR75.30-CM and the confirmed activation of STAT3 and VEGFR2 pathways, our results suggest dominance of NFkappaB as a central controller of the transcriptomic response of ECs to breast cancer cells leading to expression of cell adhesion receptors. PMID- 27666522 TI - Turning into frogs: Asymmetry in forelimb emergence and escape direction in metamorphosing anurans. AB - There is considerable debate about the pattern and origin of laterality in forelimb emergence and turning behaviour within amphibians, with the latter being poorly investigated in tadpoles around metamorphic climax. Using 6 species of metamorphosing anurans, we investigated the effect of asymmetrical spiracle location, and disturbance at the time of forelimb emergence, on the pattern of forelimb emergence. Turning behaviour was observed to assess whether motor lateralization occurred in non-neobatrachian anurans and was linked to patterns of forelimb emergence. Biases in forelimb emergence differed among species, supporting the hypothesis that asymmetrical spiracle position results in the same asymmetry in forelimb emergence. However, this pattern only occurred when individuals were undisturbed. Therefore, context at the time of the emergence of the forelimbs may be important, and might explain some discrepancies in the literature. Turning biases, unconnected to forelimb emergence, were found in Pipidae and Bombinatoridae, confirming the basal origin of lateralized behaviour among anurans. Turning direction in our metamorphs differed from the leftward bias commonly observed in tadpoles, but may be analogous to the prevalent right "handedness" among adult anurans. Therefore, the transitions occurring during metamorphosis may affect lateralized behaviour and metamorphosis may be fruitful for understanding the development of lateralization. PMID- 27666519 TI - Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration. AB - A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others. PMID- 27666524 TI - Eco-friendly p-type Cu2SnS3 thermoelectric material: crystal structure and transport properties. AB - As a new eco-friendly thermoelectric material, copper tin sulfide (Cu2SnS3) ceramics were experimentally studied by Zn-doping. Excellent electrical transport properties were obtained by virtue of 3-dimensionally conductive network for holes, which are less affected by the coexistence of cubic and tetragonal phases that formed upon Zn subsitition for Sn; a highest power factors ~0.84 mW m-1 K-2 at 723 K was achieved in the 20% doped sample. Moreover, an ultralow lattice thermal conductivity close to theoretical minimum was observed in these samples, which could be related to the disordering of atoms in the coexisting cubic and tetragonal phases and the interfaces. Thanks to the phonon-glass-electron-crystal features, a maximum ZT ~ 0.58 was obtained at 723 K, which stands among the tops for sulfide thermoelectrics at the same temperature. PMID- 27666523 TI - Electronic properties of MoS2/MoOx interfaces: Implications in Tunnel Field Effect Transistors and Hole Contacts. AB - In an electronic device based on two dimensional (2D) transitional metal dichalcogenides (TMDs), finding a low resistance metal contact is critical in order to achieve the desired performance. However, due to the unusual Fermi level pinning in metal/2D TMD interface, the performance is limited. Here, we investigate the electronic properties of TMDs and transition metal oxide (TMO) interfaces (MoS2/MoO3) using density functional theory (DFT). Our results demonstrate that, due to the large work function of MoO3 and the relative band alignment with MoS2, together with small energy gap, the MoS2/MoO3 interface is a good candidate for a tunnel field effect (TFET)-type device. Moreover, if the interface is not stoichiometric because of the presence of oxygen vacancies in MoO3, the heterostructure is more suitable for p-type (hole) contacts, exhibiting an Ohmic electrical behavior as experimentally demonstrated for different TMO/TMD interfaces. Our results reveal that the defect state induced by an oxygen vacancy in the MoO3 aligns with the valance band of MoS2, showing an insignificant impact on the band gap of the TMD. This result highlights the role of oxygen vacancies in oxides on facilitating appropriate contacts at the MoS2 and MoOx (x < 3) interface, which consistently explains the available experimental observations. PMID- 27666525 TI - Disaster Preparedness Among University Students in Guangzhou, China: Assessment of Status and Demand for Disaster Education. AB - OBJECTIVE: This study had 2 aims. First, we evaluated the current levels of disaster preparedness among university students in southern China. Second, we assessed students' demands for future disaster education. In addition, we examined the influence of demographic factors on current disaster preparedness status and demand. METHODS: A cross-sectional design was used. The data were collected from 1893 students in 10 universities in the Guangzhou Higher Education Mega (GHEM) center. A self-administered questionnaire developed for this study was administered to assess the current status and demand for disaster education. RESULTS: The results are based on 1764 valid questionnaires. Among the participants, 77.8% reported having had disaster education experiences before, 85.5% indicated their desire for a systematic disaster course, and 75.4% expressed their willingness to take such a course upon its availability. The total mean score for demand for disaster course content (5-point Likert scale) was 4.17+/-0.84, with items relating to rescue skills given the highest scores. These results suggested that students had high desires for disaster preparedness knowledge, especially knowledge concerning rescue skills. We observed significant differences in disaster education experiences between male and female students and across programs, school years, and home locations. Furthermore, we observed significant differences in demand for disaster course content between male and female students and across universities, student programs, years of school, and students' majors. CONCLUSION: A systematic disaster course focused on rescue skills is needed by all types of universities. To improve the disaster education system in universities, disaster drills should be performed on a semester basis as a refresher and to enhance disaster preparedness. The government and universities should support building a simulated disaster rescue center and recruit faculty from the emergency department, especially those who have had disaster relief experience. (Disaster Med Public Health Preparedness. 2017;11:310 317). PMID- 27666526 TI - Dairy food products: good or bad for cardiometabolic disease? AB - Prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasingly and is a key risk for CVD development, now recognised as the leading cause of death globally. Dietary strategies to reduce CVD development include reduction of saturated fat intake. Milk and dairy products are the largest contributors to dietary saturated fats in the UK and reduced consumption is often recommended as a strategy for risk reduction. However, overall evidence from prospective cohort studies does not confirm a detrimental association between dairy product consumption and CVD risk. The present review critically evaluates the current evidence on the association between milk and dairy products and risk of CVD, T2DM and the metabolic syndrome (collectively, cardiometabolic disease). The effects of total and individual dairy foods on cardiometabolic risk factors and new information on the effects of the food matrix on reducing fat digestion are also reviewed. It is concluded that a policy to lower SFA intake by reducing dairy food consumption to reduce cardiometabolic disease risk is likely to have limited or possibly negative effects. There remain many uncertainties, including differential effects of different dairy products and those of differing fat content. Focused and suitably designed and powered studies are needed to provide clearer evidence not only of the mechanisms involved, but how they may be beneficially influenced during milk production and processing. PMID- 27666527 TI - Remediation of Hg(II) from solutions using Cajanus cajan husk as a new sorbent. AB - In this work, biosorption of mercury(II) from solutions by normal and chemically modified husk of Cajanus cajan has been explored under batch conditions. The thermogravimetric analysis of the normal biosorbent showed a surface water loss of 6.56%, 9.26% volatile matter, and 81.81% organic matter. The scanning electron microscope image indicates that the biosorbent exhibited irregular and porous structures. The Fourier transform infra-red spectrum confirmed the presence of functional groups which are responsible for biosorption of mercury (II) from solutions after activation. The influence of initial pH of solutions, initial metal concentrations, and temperature on mercury(II) uptake by the biosorbents was evaluated. The biosorption followed the Langmuir model. Maximum metal uptake was obtained as 68 and 82 mg/g for an initial mercury(II) concentration of 150 mg/L for normal and chemically activated biosorbents, respectively, at a most favorable solution pH of 5.5. The kinetics of sorption obeyed the pseudo-second order model. An endothermic nature of the biosorption process was observed. A two stage biosorber reduced the consumption of the biosorbents by 3.49% and 16.52% for 100 and 150 mg/L, respectively. The novelty of the work is C. cajan husk proves to be a potential biosorbent for mercury(II) from solutions. PMID- 27666528 TI - Two-step phase-shifting SPIDER. AB - Comprehensive characterization of ultrafast optical field is critical for ultrashort pulse generation and its application. This paper combines two-step phase-shifting (TSPS) into the spectral phase interferometry for direct electric field reconstruction (SPIDER) to improve the reconstruction of ultrafast optical fields. This novel SPIDER can remove experimentally the dc portion occurring in traditional SPIDER method by recording two spectral interferograms with pi phase shifting. As a result, the reconstructed results are much less disturbed by the time delay between the test pulse replicas and the temporal widths of the filter window, thus more reliable. What is more, this SPIDER can work efficiently even the time delay is so small or the measured bandwidth is so narrow that strong overlap happens between the dc and ac portions, which allows it to be able to characterize the test pulses with complicated temporal/spectral structures or narrow bandwidths. PMID- 27666529 TI - Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction. AB - The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory "GO" signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90 ms) after the "GO" signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60 ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context. PMID- 27666530 TI - Etoposide induced cytotoxicity mediated by ROS and ERK in human kidney proximal tubule cells. AB - Etoposide (ETO) is a commonly used chemotherapeutic drug that inhibits topoisomerase II activity, thereby leading to genotoxicity and cytotoxicity. However, ETO has limited application due to its side effects on normal organs, especially the kidney. Here, we report the mechanism of ETO-induced cytotoxicity progression in human kidney proximal tubule (HK-2) cells. Our results show that ETO perpetuates DNA damage, activates mitogen-activated protein kinase (MAPK), and triggers morphological changes, such as cell and nuclear swelling. When NAC, a well-known reactive oxygen species (ROS) scavenger, is co-treated with ETO, it inhibits an ETO-induced increase in mitochondrial mass, mitochondrial DNA (ND1 and ND4) copy number, intracellular ATP level, and mitochondrial biogenesis activators (TFAM, PGC-1alpha and PGC-1beta). Moreover, co-treatment with ETO and NAC inhibits ETO-induced necrosis and cell swelling, but not apoptosis. Studies using MAPK inhibitors reveal that inhibition of extracellular signal regulated kinase (ERK) protects ETO-induced cytotoxicity by inhibiting DNA damage and caspase 3/7 activity. Eventually, ERK inhibitor treated cells are protected from ETO-induced nuclear envelope (NE) rupture and DNA leakage through inhibition of caspase activity. Taken together, these data suggest that ETO mediates cytotoxicity in HK-2 cells through ROS and ERK pathways, which highlight the preventive avenues in ETO-induced cytotoxicity in kidney. PMID- 27666531 TI - Highly conductive and pure gold nanostructures grown by electron beam induced deposition. AB - This work introduces an additive direct-write nanofabrication technique for producing extremely conductive gold nanostructures from a commercial metalorganic precursor. Gold content of 91 atomic % (at. %) was achieved by using water as an oxidative enhancer during direct-write deposition. A model was developed based on the deposition rate and the chemical composition, and it explains the surface processes that lead to the increases in gold purity and deposition yield. Co injection of an oxidative enhancer enabled Focused Electron Beam Induced Deposition (FEBID)-a maskless, resistless deposition method for three dimensional (3D) nanostructures-to directly yield pure gold in a single process step, without post-deposition purification. Gold nanowires displayed resistivity down to 8.8 MUOmega cm. This is the highest conductivity achieved so far from FEBID and it opens the possibility of applications in nanoelectronics, such as direct-write contacts to nanomaterials. The increased gold deposition yield and the ultralow carbon level will facilitate future applications such as the fabrication of 3D nanostructures in nanoplasmonics and biomolecule immobilization. PMID- 27666532 TI - Relationships between functional diversity and aboveground biomass production in the Northern Tibetan alpine grasslands. AB - Functional diversity, the extent of functional differences among species in a community, drives biodiversity-ecosystem function (BEF) relationships. Here, four species traits and aboveground biomass production (ABP) were considered. We used two community-wide measures of plant functional composition, (1) community weighted means of trait values (CWM) and (2) functional trait diversity based on Rao's quadratic diversity (FDQ) to evaluate the effects of functional diversity on the ABP in the Northern Tibetan alpine grasslands. Both species and functional diversity were positively related to the ABP. Functional trait composition had a larger predictive power for the ABP than species diversity and FDQ, indicating a primary dependence of ecosystem property on the identity of dominant species in our study system. Multivariate functional diversity was ineffective in predicting ecosystem function due to the trade-offs among different traits or traits selection criterions. Our study contributes to a better understanding of the mechanisms driving the BEF relationships in stressed ecosystems, and especially emphasizes that abiotic and biotic factors affect the BEF relationships in alpine grasslands. PMID- 27666533 TI - An evaluation of multiplex bead-based analysis of cytokines and soluble proteins in archived lithium heparin plasma, EDTA plasma and serum samples. AB - OBJECTIVE: To assess the usability of archived plasma and serum by multiplex (Luminex) analysis of circulating proteins (analytes) by evaluating the day to day variation, the effect of several freeze-thaw cycles, and the influence of the media and choice of anticoagulant. METHODS: Nineteen analytes in plasma and serum from 86 head and neck cancer patients and 33 controls were evaluated: EGFR, leptin, OPN, VEGFR-1, VEGFR-2, IL-2, IL-13, PDGF-bb, TNF, PAI-1, SDF-1a, IL-4, IL 6, IL-8, eotaxin, G-CSF, VEGF, GRO-a, and HGF. RESULTS: The correlation between measurements of the same samples analyzed on different dates was reasonable. However, samples run on different dates could exhibit different absolute values. The 75th percentile of the fold differences for samples run on different dates was 2.2. No significant difference was found between one and four freeze-thaw cycles (except for HGF), and the correlation was high. We found significant differences in mean concentrations of the majority of analytes in different media and with different anticoagulants. Only the following analytes did not show difference in mean concentrations: EDTA plasma vs. serum: leptin and VEGFR-2, LH plasma vs. serum: IL-2, IL-13, and VEGF, LH plasma levels vs. EDTA plasma: IL-2 and IL-4. CONCLUSION: Stored serum, LH plasma, and EDTA plasma from clinical trials can be used for analysis of circulating cytokines and proteins. Variations in measurements occur, but are within reasonable ranges. The optimal type of media depends on the analytes, as different analytes have low number of measurements below the lower limit of quantification and higher dynamic ranges in different media. PMID- 27666534 TI - Heterozygous inactivating CaSR mutations causing neonatal hyperparathyroidism: function, inheritance and phenotype. AB - BACKGROUND: Homozygous inactivating mutations of the calcium-sensing receptor (CaSR) lead to neonatal severe hyperparathyroidism (NSHPT), whereas heterozygous inactivating mutations result in familial hypocalciuric hypercalcemia (FHH). It is unknown why in some cases heterozygous CaSR mutations cause neonatal hyperparathyroidism (NHPT) clinically similar to NSHPT but with only moderately elevated serum calcium. METHODS: A literature survey was conducted to identify patients with heterozygous CaSR mutations and NHPT. The common NHPT CaSR mutants R185Q and R227L were compared with 15 mutants causing only FHH in the heterozygous state. We studied in vitro calcium signaling including the functional consequences of co-expression of mutant and wild-type (wt) CaSR, patients' phenotype, age of disease manifestation and mode of inheritance. RESULTS: All inactivating CaSR mutants impaired calcium signaling of wt-CaSR regardless of the patients' clinical phenotype. The absolute intracellular calcium signaling response to physiologic extracellular calcium concentrations in vitro showed a high correlation with patients' serum calcium concentrations in vivo, which is similar in NHPT and FHH patients with the same genotype. Pedigrees of FHH families revealed that paternal inheritance per se does not necessarily lead to NHPT but may only cause FHH. CONCLUSIONS: There is a significant correlation between in vitro functional impairment of the CaSR at physiologic calcium concentrations and the severity of alterations in calcium homeostasis in patients. Whether a particular genotype leads to NHPT or FHH appears to depend on additional predisposing genetic or environmental factors. An individual therapeutic approach appears to be warranted for NHPT patients. PMID- 27666535 TI - ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome. AB - Thyroid cancer is the most common endocrine malignancy giving rise to one of the most indolent solid cancers, but also one of the most lethal. In recent years, systematic studies of the cancer genome, most importantly those derived from The Cancer Genome Altas (TCGA), have catalogued aberrations in the DNA, chromatin, and RNA of the genomes of thousands of tumors relative to matched normal cellular genomes and have analyzed their epigenetic and protein consequences. Cancer genomics is therefore providing new information on cancer development and behavior, as well as new insights into genetic alterations and molecular pathways. From this genomic perspective, we will review the main advances concerning some essential aspects of the molecular pathogenesis of thyroid cancer such as mutational mechanisms, new cancer genes implicated in tumor initiation and progression, the role of non-coding RNA, and the advent of new susceptibility genes in thyroid cancer predisposition. This look across these genomic and cellular alterations results in the reshaping of the multistep development of thyroid tumors and offers new tools and opportunities for further research and clinical development of novel treatment strategies. PMID- 27666536 TI - Gondwanan conifer clones imperilled by bushfire. AB - Global increases in fire frequency driven by anthropogenic greenhouse emissions and land use change could threaten unique and ancient species by creeping into long-term fire refugia. The perhumid and mountainous western half of Tasmania is a globally important refugium for palaeo-endemic, fire intolerant lineages, especially conifers. Reproductive strategy will be crucial to the resilience of these organisms under warmer, dryer and more fire prone climates. This study analysed clonal versus sexual reproduction in old growth plots dominated by the palaeo-endemic conifer Athrotaxis cupressoides (Cupressaceae), a species that lacks any traits to tolerate frequent landscape fire. Across most of the seven plots the amount of sexually derived individuals was lower than clonally derived with, on average, 60% of all stems belonging to the same multi-locus lineage (MLL) (i.e. were clonal). Some MLLs were large spanning over 10 s of metres and consisted of up to 62 stems. The high mortality after fire and the rarity of sexual regeneration means that the range of this fire-intolerant species is likely to contract under enhanced fire regimes and has a limited capacity to disperse via seed to available fire refugia in the landscape. PMID- 27666537 TI - The challenge of fertility preservation in cancer patients II: a themed issue of Future Oncology. PMID- 27666538 TI - Molecular Modeling and Structural Analysis of Some Snake Venom Specific Toxin Proteins and Cognate Non-Toxin Proteins of Other Chordates. AB - BACKGROUND: Protein three-dimensional structures are very much important in terms of functional and evolutionary context. In the present work we evaluated the snake venom constituent cytotoxin, short neurotoxin and related non-toxin proteins of other chordates with reference to structure prediction, validation of the models, distribution of secondary structural elements, hydrophobicity molecular surface analysis, functional annotation and functionally critical binding site identification with the assistance of different bioinformatical tools. METHODS: Homology models have been generated with the help of Swiss-model and ITASSER suite during the present study. Afterwards the refined structural models were validated with standard methods. For functional annotation of protein molecules we used Protein Information Resource (PIR) database. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) was determined using the COACH program. RESULTS: Structural analysis of snake venom toxin proteins and related non-toxin proteins of other chordates elucidated their structural level conservation of molecular structural surfaces and biophysical characteristics to different extents. Different structural level improvement strategies were observed which are necessary for better system dependent adaptation to diverse biological environment and functional necessities of these protein molecules. CONCLUSION: Molecular models and their structural characterization of these proteins as documented in this study may provide a valuable aid for drug designing in future. PMID- 27666539 TI - Frontline intensive chemotherapy improves outcome in young, high-risk patients with follicular lymphoma: pair-matched analysis from the Czech Lymphoma Study Group Database. AB - Optimal frontline treatment in younger high tumor-burden risk follicular lymphoma patients remains a challenge given the reduced efficacy of standard immunochemotherapy (R-CHOP) in widespread disease and unclear role of intensive induction. The retrospective non-randomized pair-matched (1:3) analysis compared 48 intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) patients receiving intensive rituximab sequential chemotherapy (R-SQ) with 144 random controls (R-CHOP) matched for age, FLIPI score, and maintenance delivery. Complete response rates were 91.7% and 74.1%, respectively (p = .038). After a median follow-up of 8.8 (R-SQ) and 6.5 years (R-CHOP), 5-year time to treatment failure, progression-free survival, and overall survival were 80.9%, 83.2%, and 100% and 57.5%, 60.3%, and 92.1% (p = .0044; p = .0047; p = .22), respectively. Intensive treatment was accompanied by higher acute hematologic toxicity and infections, comparable non-hematologic toxicity, and incidence of secondary malignancies. Intensive induction demonstrates superior long-term disease control compared to R-CHOP, with higher acute hematologic toxicity, but without acute treatment-related mortality. Further studies are needed to define ultra-high-risk FL patients benefiting most from treatment intensity. PMID- 27666540 TI - Management of gastrointestinal perforation from blunt and penetrating abdominal trauma in children: analysis of 96 patients. AB - AIM: The objective of the present study was to evaluate the diagnostic methods, concomitant organ injuries, factors affecting mortality and morbidity, treatment methods, and outcomes of patients treated for traumatic gastrointestinal (GI) perforation. MATERIALS AND METHODS: We conducted a retrospective review of the medical records of 96 patients who had been treated for GI perforation between January 2000 and October 2015. Data were collected and organised according to the following categories: general patient information, age, gender, hospitalisation period, trauma mechanisms, concomitant injuries, radiological assessment, diagnosis and treatment methods, treatment forms, and complications. The cases were divided into two groups, blunt and penetrating traumas, and the patients within each group were compared. Colorectal trauma cases were not included in this study. Patients suspected of a GI perforation were assessed by standing plain abdominal radiograph (SPAR) and ultrasound scan (US). Patients who had a normal SPAR, and showed free or viscous fluid in the abdomen on US underwent computed tomography (CT) scanning. Surgery was performed if patients displayed free air in the abdomen on a SPAR or CT scan, showed viscous fluid without any additional injury, provided normal radiological images but displayed signs of peritonitis, or were clinically unstable. The patients were scored according to the Injury Severity Score (ISS) system. RESULTS: In total, 96 patients, with an average age of 10.3 +/- 4 years (1-17 years) and diagnosed with a GI perforation, were reviewed retrospectively. The patients included 88 (91 %) males and 8 (9 %) females. The presence of free air on SPAR was detected in 42 (52 %) patients, whereas no free air was detected in 39 (48 %) patients. Non-specific significant findings were detected in 45 (76 %) out of 59 patients by USS, and in 78 % of patients by CT (viscous fluid, fluid, free air). The most affected organ was the ileum, which was detected in 37 (39 %) patients. Primary repair was performed on 71 (74 %) patients, while resection was performed on 22 (23 %); 3 (3 %) patients underwent an ostomy. Ten (10 %) patients experienced complications and five (5 %) patients died. The ISS scores for blunt and penetrating traumas were 14, 15 and no significant difference was detected between the scores (p > 0.05). CONCLUSIONS: Although the complication rate for patients with penetrating trauma was higher than for those with blunt trauma, the rate of mortality increased in patients with blunt trauma. Free air may not be detected by SPAR even if a GI perforation exists. Since diagnostic challenges may increase the rate of mortality and morbidity in GI perforations, we believe that a combination of radiological imaging and rapid abdominal examination is important in cases where SPAR cannot detect free air. PMID- 27666542 TI - Relieving geometrical frustration through doping in the Dy1-x Ca x BaCo4O7 swedenborgites. AB - The geometrically frustrated antiferromagnet DyBaCo4O7 is investigated through a combination of x-ray diffraction, magnetization and dielectric measurements. Systematic doping in the series Dy1-x Ca x BaCo4O7 causes a lifting of the geometrical frustration resulting in a structural transition from a trigonal P31c to an orthorhombic Pbn2 1 symmetry at x = 0.4. This structural transition can also be accessed as a function of temperature, and all our orthorhombic specimens exhibit this transition at elevated temperatures. The temperature at which this structural transition occurs is observed to scale linearly with the mean ionic radius of the R site ion. However, CaBaCo4O7 which has an equal number of Co2+ and Co3+ ions clearly violates this quasilinear relationship, indicating that charge ordering could also play a critical role in stabilizing the orthorhombic distortion in this system. Using thermoremanent magnetization measurements to circumvent the problem of the large paramagnetic background arising from Dy3+ ions, we chart out the phase diagram of the Dy1-x Ca x BaCo4O7 series. PMID- 27666541 TI - Enhanced anti-tumor immunity against breast cancer induced by whole tumor cell vaccines genetically modified expressing alpha-Gal epitopes. AB - Whole tumor cell vaccines have shown much promise, but demonstrated poor efficiency in phase III trials. In this study, we modified MDA-MB-231 tumor cells (MDA-MB-231Gal+) to express alpha-1, 3-galactosyltransferase (alpha-1, 3-GT) protein, to potentially enhance antitumor effect of whole tumor cell vaccines. MDA-MB-231 tumor cell vaccines were transfected with a reconstructed lentiviral containing alpha-1, 3-GT genes. Tumor growth, tumorigenesis and survival of Hu NOD-SCID mice were observed when tumor-bearing mice were injected with tumor cell vaccines. Proliferation and apoptosis in MDA-MB-231 tumor xenografts were observed by immunohistochemistry. The levels of cytokine secretion in the serum of mice were tested by ELISA. CD8+ T cells infiltrating tumors were assessed by flow cytometry. MDA-MB-231Gal+ cells expressed active alpha-1, 3-GT and produced alpha-Gal in vitro. MDA-MB-231Gal+ cell vaccines suppressed tumor growth and tumorigenesis in immunized Hu-NOD-SCID mice. Additionally, decrease of TGF-beta, IL-10 and increase of INF-gamma, IL-12 were observed in tumor cell vaccinated mice. Furthermore, the cell vaccines enhanced infiltration of cytotoxic CD8+ T cells in the tumor microenvironment of immunized mice. The MDA-MB-231Gal+ cell vaccines modified alpha-1, 3-GT genes improved the antitumor effect. PMID- 27666544 TI - [Methylation Status of the SOCS3 Gene Promoter in H2228 Cells and ?EML4-ALK positive Lung Cancer Tissues]. AB - BACKGROUND: The EML4-ALK fusion gene is a newly discovered driver gene of non small cell lung cancer and exhibits special clinical and pathological features. The JAK-STAT signaling pathway, an important downstream signaling pathway of EML4 ALK, is aberrantly sustained and activated in EML4-ALK-positive lung cancer cells fusion gene, but the underlying reason remains unknown. The suppressor of cytokine signaling (SOCS) is a negative regulatory factor that mainly inhibits the proliferation, differentiation, and induction of apoptotic cells by inhibiting the JAK-STAT signaling pathway. The aberrant methylation of the SOCS gene leads to inactivation of tumors and abnormal activation of the JAK2-STAT signaling pathway. The aim of this study is to investigate the methylation status of the SOCS3 promoter in EML4-ALK-positive H2228 cells and lung cancer tissues. METHODS: The methylation status of the SOCS3 promoter in EML4-ALK-positive H2228 lung cancer cells and lung cancer tissues was detected by methylation-specific PCR (MSP) analysis and verified by DNA sequencing. The expression levels of SOCS3 in H2228 cells were detected by Western blot and Real-time PCR analyses after treatment with the DNA methyltransferase inhibitor 5'-Aza-dC. RESULTS: MSP and DNA sequencing assay results indicated the presence of SOCS3 promoter methylation in H2228 cells as well as in three cases of seven EML4-ALK-positive lung cancer tissues. The expression level of SOCS3 significantly increased in H2228 cells after 5'-Aza-dC treatment. CONCLUSIONS: The aerrant methylation of the SOCS3 promoter region in EML4-ALK (+) H2228 cells and lung cancer tissues may be significantly involved in the pathogenesis of EML4-ALK-positive lung cancer. PMID- 27666545 TI - [Effects of miR-424 on Proliferation and Migration Abilities in Non-small Cell Lung Cancer A549 Cells and Its Molecular Mechanism]. AB - BACKGROUND: The inhibitory ability of miR-424 on the proliferation of renal carcinoma cell and the migration and invasion of cancer cells has been widely explored and demonstrated. However, the effects of miR-424 on non-small cell lung cancer (NSCLC) have not been systematically examined. In this study, detected the growth and invasion effect of miR-424 in NSCLC A549 cell. The migration and molecular mechanism of this cell are also detected. METHODS: NSCLC A549 cell was transfected with miR-424 and its inhibitor. After transfection, the proliferation ability of A549 cell was detectedby CCK8 assay. Then, the migration ability in A549 cell was detected by migration assays. Furthermore, the expression level of MMP2 and MMP9 in A549 was detected by Western blot and immune fluorescence. The 3'UTR of E2F6 was cloned into luciferase reporter vector and its enzymatic activitywas detected to verify whether miR-424 can target E2F6. The expression level of E2F6 in a549 cell after transfecing with miR-424 was detected by Western blot. RESULTS: After transfection of miR-424, the proliferation and migration abilities were remarkably decreased and the expression level of MMP-2 and MMP-9 were down-regulated in A549. Moreover, MiR-424 inhibited the enzymatic activity of luviferase reporter vector of E2F6. Specifically, the expression level of E2F6 was down-regulated in A549. CONCLUSIONS: miR-424 can inhibit the proliferation and migration abilities of A549 by negatively regulating the expression of E2F6.?. PMID- 27666543 TI - The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. AB - Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer. PMID- 27666547 TI - [Clinical Assessment of Chemosensitivity Test in Xeno-free Culture of Autologous ?Malignant Effusion Cells from Patients with Advanced Lung Adenocarcinoma]. AB - BACKGROUND: A great individual differences to chemotherapeutic effects existed in the patient with advanced lung cancer. How to choose the optimum regimens to achieve the individuation and maximum effect of chemotherapy for lung cancer is worth exploring. The study was designed to examine the effect of ex vitro chemo sensitivity assay in xeno-free culture of autologous malignant effusion cells from patients with advanced lung adenocarcinoma. METHODS: The 50 treatment-naive patients with lung adenocarcinoma complicated with malignant pleural or pericardial effusions were enrolled. Effusions of all cases had been controlled by closed drainage and 300 mL-500 mL of which were retained under sterile condition from 25 cases (Chemo-sensitivity group). Primary malignant effusion cells were isolated from autologous effusions of the patients. Then, xeno-free culture (average 11 days) were intervened with 8 chemotherapeutic drugs commonly used in clinical practice and were determined by CCK-8 assay. Optimum regimens were selected for chemotherapy based on the results of chemosensitivity test. As a contrast, chemotherapy regimens for the other 25 patients (Control group) were on the basis of physician's clinical experience. RESULTS: After four cycles of chemotherapy, in Chemo-sensitivity group, 17 (68.0%) cases were determined for partial response (PR), 5 (20.0%) cases for stable disease (SD), and the objective response rate (ORR) was 68.0%, the disease control rate (DCR) was 88.0%. Meanwhile, in Control group, 9 (36.0%) cases were determined for PR, 7 (28.0%) cases for SD, and, the ORR was 36.0%, the DCR was 64.0%. There were significant differences between the two groups in ORR and DCR (P<0.05). To the end of follow up, there were 21 cases of death in Chemo-sensitivity group as well as 22 cases in Control group. The mean progression-free survival (PFS) in Chemo-sensitivity group and Control group respectively were 10.0 months and 5.8 months, and the mean overall survival (OS) in the two groups were 30.2 months and 21.2 months respectively. There were also significant differences between the two groups in PFS and OS (P<0.05). Furthermore, the adverse reactions in both groups were mild and controllable. CONCLUSIONS: Xeno-free culture of autologous malignant effusion cells from patients with advanced lung adenocarcinoma and ex vitro chemo sensitivity assay are beneficial to the rational choices of chemotherapeutic agents used in patients with lung adenocarcinoma complicated with malignant effusions, which is a worthy trial in personalized cell culture for individualized cancer therapy and further studies. PMID- 27666546 TI - [Localizating and Extracting Small Peripheral Nodules of Lung with Simulating ?Radiaotherapy Combining Methylene Blue Staining]. AB - BACKGROUND: With the extensively application of HRCT (high resolution CT) and the popularization of early lung cancer screening, the proportion of small nodullar lung cancer to be operated increases rapidly. Identifying the focus lesions quickly and accurately in operation has shown to be a challenge. We carried out this research trying to make use of and evaluate a new method that localizaes and extracts small peripheral pulmonary nodules by way of simulating radiaotherapy combining methylene blue staining. METHODS: From February 2012 to January 2015, 97 patients with 100 peripheral pulmonary nodules <=10 mm in size were simulated puncturing using a radiotherapy planning. When the anaesthesia came into use, methylene blue dye was injected to the virtually identified point corresponding to the surface point, according to the angle and depth previously computed by the radiotherapy planning. The video-assisted thoracoscopic surgery (VATS) wedge resections of the marked lesions were undertaken and the specimens were sent for frozen pathologic examination. The interval time from anesthesia-completing to puncture and injection, The interval time from methylene blue injection to identifying the stained area and the distances between the centre point of the stains and edge of coloured lesion were recorded. RESULTS: Our preoperative localization procedure was successful in 96 of 100 (96%) nodules. The interval time from anesthesia-completing to puncture and injection of methylene blue were (4.85+/-1.25) min. The interval time from methylene blue injection to identifying the stained area was (16.36+/-2.36) min. The distances between the centre point of the stains and edge of coloured lesion were (4.78+/-2.51) mm. No complication was observed in all participants. CONCLUSIONS: The new method of locating peripheral pulmonary nodules by simulating simulating radiaotherapy combining methylene blue staining has a high success rate and no complication for localizing small peripheral pulmonary lesions, avoiding the fear and pain of the patients untaken puncture without anaesthesia reducing radial damage. PMID- 27666548 TI - [Utility of NSE, ProGRP and LDH in Diagnosis and Treatment?in Patients with Small Cell Lung Cancer]. AB - BACKGROUND: Small cell lung cancer (SCLC) is a rapidly growing tumor with characteristic of neuroendocrine cellular function. Neuron specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP) and lactic dehydrogenase (LDH) are valuable in diagnosis and treatment of SCLC. By analyzing the variation of NSE, ProGRP and LDH before and after treatment, the aim of this study is to investigate the efficacy of tumor markers in diagnostic staging, therapeutic evaluation and prediction of disease relapsing. METHODS: Patients with SCLC who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic (includes NSE, ProGRP and LDH level before and after 2 cycles chemotherapy), efficacy evaluation, progression-free survival (PFS) were analyzed. RESULTS: Before treatment, Serum NSE, ProGRP and LDH in patients with extensive disease (ED) were significantly higher than those with limited disease (LD)(all P<0.005); NSE level increased obviously accompanied by increase of lymph nodes stage in LD group (P=0.010); Patients with weight reduction when diagnosis had higher NSE and LDH than those without loss of weight (P=0.032, P=0.014). After 2 cycles chemotherapy, decrease of NSE and ProGRP in effective group was higher than which in stable and ineffective groups (P=0.015, P=0.002). The relapse risk was lower in patients who accepted >4 cycles chemotherapy and with obvious decrease of ProGRP than those who accepted <=4 cycles chemotherapy and with less obvious decrease of ProGRP in LD group; ED patients with no more than 2 distant metastasis, normal LDH level before treatment and obvious decrease of ProGRP after chemotherapy had lower short term relapse risk. In addition, the types of relapse (sensitive relapse, drug resistance relapse and refractory relapse) were negatively correlated with decrease of ProGRP (P=0.044). By multivariate analysis, numbers of chemotherapy cycle was independent prognostic factor for PFS in LD SCLC; numbers of distant metastasis and decrease of ProGRP were independent prognostic factors for PFS in ED SCLC. CONCLUSIONS: Increase level of serum tumor markers is related to tumor burden. Decrease level of ProGRP after treatment may prognose efficacy and relapse risk. PMID- 27666549 TI - [Interventional Bronchoscopy for the Treatment of Pulmonary Sarcoma]. AB - BACKGROUND: Pulmonary sarcoma is a rare malignant tumor in soft tissues. Resection is the preferred option to treat this tumor. The aim of this study is to explore the effect of interventional bronchoscopies in the treatment of pulmonary sarcoma if the patient is inoperable. METHODS: Sixteen cases with pulmonary sarcoma were retrospectively reviewed in our hospital from November 2008 to July 2014. The mean age was (53.1+/-5.4) years old. Rigid bronchoscopy was applied for the first procedure with general anesthesia, and electronic bronchoscopy was used for the second procedure or slight patients. RESULTS: Sixteen cases, which include 10 sarcomatoid carcinoma, 2 fibrosarcoma, 2 sarcoma, 1 fibromucoid sarcoma, and 1 spindle cell synovial sarcoma, were collected in this study. Eleven cases (68.8%) were peripheral and mainly located in the right upper lobe and left lower lobe. Five cases (31.2%) were central. Of these cases, 82% (9/11) were mixed and primary tumors in pulmonary tumor. Meanwhile, 56% (9/16) were intraluminal and 69% (11/16) were metastatic in central airway. All of the four cases with whole atelectasis were completely relieved through postbronchoscopic interventions. Three of the seven cases with segment atelectasis were completely reopened; two of them were partially relieved; and the remaining two had no response. The obstructive degree, Karnofsky performance status (KPS), and shortness of breathless score improved significantly after the treatment. CONCLUSIONS: Interventional bronchoscopy could rapidly and efficiently remove endobronchial tumor, relieve airway obstruction, and improve clinical symptoms. PMID- 27666551 TI - [Erratum: Comparison of the Masaoka-Koga and The IASLC/ITMIG Proposal for The TNM Staging Systems Based on the Chinese Alliance for Research in Thymomas (ChART) Retrospective Database]. PMID- 27666554 TI - [Erratum: Pretreatment Biopsy for Histological Diagnosis and Induction Therapy in Thymic Tumors]. PMID- 27666550 TI - [Preliminary Study of Differentially Expressed Serum Peptides of Advanced NSCLC Patients Responsive to EGFR-TKI and Their Clinical Significance]. AB - BACKGROUND: This study aimed at using matrix-assisted laser desorption ionization - time of flight mass spectrometer (matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF-MS) screening the difference serum peptides during epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment and exploring their significance of advanced NSCLC patients. METHODS: Collect 102 serum samples from 34 advanced NSCLC patients, which are before TKI treatment, best effect of treatment and after progession. Peptides were extracted from the samples and then detected by MALDI-TOF-MS system to get the mass spectra. The mass spectra data was analyzed by the ClinproToolTM software to identify the different serum peptides, and then analyzed the clinical significance of peptides. RESULTS: Among the 34 patients who received TKI treatment, there were none evaluated as complete response (CR), 11 patients evaluated as PR and 23 patients evaluated as stable disease (SD), with the PFS was 8.0 months (95%CI: 6.6-11.2); overall survival (OS) was 11.4 months (95%CI: 10.6-16.5). After detected the serum from three different points of time, the result showed that they were totally different; 87 different peptide peaks were identified after analysis self-paired serum between the time of best effect and baseline, which included one statistically different [P<0.001, area under curve (AUC)>=0.9] peptide; 96 different peptide peaks were identified after analysis serum between the time of progression and baseline, which included 3 statistically different (P<0.001, AUC>=0.9) peptides; 115 different peptide peaks were identified after analysis serum between the time of progression and best effect, which included 4 statistically different (P<0.001, AUC>=0.9) peptides. CONCLUSIONS: Theserum peptides of NSCLC patients in the process of TKI treatment are dynamic and the different peptides may be associated with treatment effect and disease progression. However, the features and clinical significance of different peptides need to be validated in the future.?. PMID- 27666553 TI - [Advance in Research of Angiotensin II and Its Receptor and Malignant Tumor]. AB - Angiotensin AngII, a linear small peptide,which is composed of eight amino acids, is the main effectors of renin-angiotensin systen (Renin-angiotensin system, RAS). AngII, a main biopolypeptide of the RAS, has important pathophysiologic in effects participating in cardiac hypertrophy, vascular cell proproliferation, inflammation and tissue remodeling through G-protein-coupled receptors. In recent years, Ang II can promote tumor cell proliferation, tumor vessel formation and inhibit the differentiation of the tumor cells. This suggests that inhibit the production of AngII or block its effect is expected to become a new measure for the treatment of malignant tumors. This article reviews the advances in research on the relationship between AngII and its receptor and malignant tumor in recent years. PMID- 27666552 TI - [Advances in the Research of Autophagy in EGFR-TKI Treatment and Resistance ?in Lung Cancer]. AB - Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic. On one hand, autophagy induced by EGFR-TKI acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR-TKI. On the other hand, a high level of autophagy after treatment of EGFR-TKI can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR-TKI with autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficiency of EGFR-TKI in the treatment of cancer patients. Here we summarized the signaling pathways involved in EGFR-TKI induced autophagy, and reviewed the roles of autophagy in the treatment and chemoresistance of EGFR-TKI treatment in lung cancer. PMID- 27666555 TI - [The Role of SOCS in the Development of Tumors]. AB - Suppressor of cytokine signaling (SOCS) family proteins are a group of negative regulatory factors that plays important roles in the negative regulation of cytokine responses by terminating the activation of the JAK-STAT and other signaling pathways. The family is composed of eight structurally related proteins. mainly through the inhibition of the activation of JAK-STAT signaling pathway and regulates cell proliferation, differentiation and apoptosis. In the process of tumor progression, the promoter CG island hypermethylation, gene mutation, gene deletion and inactivation lead to the abnormal expression of SOCS protein make JAK-STAT continuous activation, resulting in the development and metastasis of tumor. Here, we review the SOCS family members found, composition and molecular structure, the domain of the function, and the latest progress of development in tumor. Based on the important role of SOCS in tumor development, SOCS as a negative regulator factor represent a kind of tumor suppressor genes, has become a new target for tumor therapy. PMID- 27666557 TI - [One Case about Primary Mediastinal Primary Mediastinal Tumor ?with Mediastinal Sarcoma and Literature Review]. AB - Primary mediastinal seminoma is a kind of germ cell malignancy outside the gonads, and it's rarer with sarcoma component. This disease which has no special clinical manifestations and imaging characteristics is difficult to identify with other mediastinal tumors and mediastinal type lung cancer. This paper reported a case of primary mediastinal seminoma with mediastinal sarcoma. Through the analysis of the diagnosis and treatment process in this patient, we will make a comprehensive review of the disease. PMID- 27666556 TI - [Tumor Cells and Micro-environment in Brain Metastases]. AB - Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis "seed and soil", that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well. In this assay, we reviewed documents concerning tumor cells, brain micro-environments and their interactions in brain metastases, aiming to provide novel insight into the treatments of brain metastases. PMID- 27666559 TI - Ipsilateral hemiparesis in ischemic stroke patients. AB - OBJECTIVES: To investigate clinical characteristics of ipsilateral hemiparesis in ischemic stroke patients. MATERIALS AND METHODS: Patients with acute ischemic stroke were prospectively examined. Ipsilateral hemiparesis was defined as hemiparesis ipsilateral to recent stroke lesions. Patients with ipsilateral hemiparesis were examined with functional neuroimaging studies including transcranial magnetic stimulation (TMS) and functional MRI. RESULTS: Of 8360 patients, ipsilateral hemiparesis was detected in 14 patients (0.17%, mean age 71+/-6 years, eight men). Lesions responsible for the recent strokes were located in the frontal cortex in three patients, corona radiata in seven, internal capsule in one, and pons in three. These lesions were located along the typical route of the corticospinal tract in all but one patient. Thirteen patients also had a past history of stroke contralateral to the recent lesions; 12 of these had motor deficits contralateral to past stroke lesions. During TMS, ipsilateral magnetic evoked potentials were evoked in two of seven patients and contralateral potentials were evoked in all seven. Functional MRI activated cerebral hemispheres ipsilaterally in eight of nine patients and contralaterally in all nine. CONCLUSIONS: Most patients with ipsilateral hemiparesis had a past history of stroke contralateral to the recent one, resulting in motor deficits contralateral to the earlier lesions. Moreover, functional neuroimaging findings indicated an active crossed corticospinal tract in all of the examined patients. Both findings suggest the contribution of the uncrossed corticospinal tract contralateral to stroke lesions as a post-stroke compensatory motor system. PMID- 27666560 TI - Eupalinolide O, a novel sesquiterpene lactone from Eupatorium lindleyanum DC., induces cell cycle arrest and apoptosis in human MDA-MB-468 breast cancer cells. AB - Sesquiterpene lactones have been confirmed to have potential antitumor activity. Here, we demonstrated that Eupalinolide O (EO), a novel sesquiterpene lactone isolated from Eupatorium lindleyanum DC., showed significant anticancer activity against human MDA-MB-468 breast cancer cells. The cytotoxicity induced by EO was mediated by induction of apoptosis. Flow cytometric analysis demonstrated that EO treatment resulted in loss of the mitochondrial membrane potential in cancer cells which is regarded as a hallmark of apoptosis. Further study demonstrated that EO induced apoptotic cell death in the MDA-MB-468 cells through the activation of caspases. The effect of EO on the induction of apoptosis was significantly prevented by the treatment of pan-caspase inhibitor Z-VAD-FMK. We also found that EO treatment resulted in cell cycle arrest in the G2/M phase. The expression of cell cycle-related proteins (cyclin B1 and cdc2) was significantly decreased. Furthermore, the suppression of the Akt pathway in the MDA-MB-468 cells was observed. Collectively, EO suppressed the growth of the MDA-MB-468 cells possibly by cell cycle arrest in the G2/M phase and the induction of caspase-dependent apoptosis. These results suggest that EO is a promising natural compound for breast cancer therapy. PMID- 27666558 TI - The Binding Site Barrier Elicited by Tumor-Associated Fibroblasts Interferes Disposition of Nanoparticles in Stroma-Vessel Type Tumors. AB - The binding site barrier (BSB) was originally proposed to describe the binding behavior of antibodies to cells peripheral to blood vessels, preventing their further penetration into the tumors. Yet, it is revisited herein to describe the intratumoral cellular disposition of nanoparticles (NPs). Specifically, the BSB limits NP diffusion and results in unintended internalization of NPs by stroma cells localized near blood vessels. This not only limits the therapeutic outcome but also promotes adverse off-target effects. In the current study, it was shown that tumor-associated fibroblast cells (TAFs) are the major component of the BSB, particularly in tumors with a stroma-vessel architecture where the location of TAFs aligns with blood vessels. Specifically, TAF distance to blood vessels, expression of receptor proteins, and binding affinity affect the intensity of the BSB. The physical barrier elicited by extracellular matrix also prolongs the retention of NPs in the stroma, potentially contributing to the BSB. The influence of particle size on the BSB was also investigated. The strongest BSB effect was found with small (~18 nm) NPs targeted with the anisamide ligand. The uptake of these NPs by TAFs was about 7-fold higher than that of the other cells 16 h post-intravenous injection. This was because TAFs also expressed the sigma receptor under the influence of TGF-beta secreted by the tumor cells. Overall, the current study underscores the importance of BSBs in the delivery of nanotherapeutics and provides a rationale for exploiting BSBs to target TAFs. PMID- 27666561 TI - Effect of Cosurfactants on the Interfacial Hydration of CTAB Quaternary Reverse Micelle Probed Using Excited State Proton Transfer. AB - It has been proven previously that the negatively charged photoacid 8 hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) resides at the interface of the cationic reverse micelle (RM) cetyltrimethylammonium bromide (CTAB)/octanol/water/cyclohexane and is a potential reporter of hydration through the excited state proton transfer (ESPT) process. However, the ESPT dynamics monitored by the pump-probe study was limited to the ultrafast timescale and hence did not report any discernible ESPT signature. Herein, we reinvestigate the ESPT behavior using fluorescence spectroscopy in the nanosecond timescale and at different values of w0 (=[water]/[surfactant]). We clearly observed distinct w0 dependent ESPT signatures analogous to conventional ternary cationic RMs implying considerable interfacial hydration. The results agree with a recent molecular simulation study, where significant penetration of water molecules into the interface was predicted for the CTAB quaternary RM. Moreover, we also found that the ESPT dynamics and the fluorescence anisotropy decay of HPTS depend differentially on the octanol/CTAB ratio (p0). The ESPT process was found to be disfavored, whereas the anisotropy decay accelerates upon the increase in p0 values. Our analysis indicates that with the increase in the octanol concentration, dehydrated regions enrich gradually at the interface. However, the increase in octanol concentration may reduce the effective electrostatic potential experienced by the probe and thus may result in faster rotational relaxation. PMID- 27666562 TI - Relationship between polycystic ovary syndrome and ancestry in European Americans. AB - OBJECTIVE: To determine whether European Americans with polycystic ovary syndrome (PCOS) exhibit genetic differences associated with PCOS status and phenotypic features. DESIGN: Case-control association study in European Americans. SETTING: Academic center. SUBJECT(S): Women with PCOS diagnosed with the use of the National Institutes of Health criteria (n = 532) and control women with regular menstrual cycles and no evidence of hyperandrogenism (n = 432). INTERVENTION(S): Blood was drawn for measurement of sex steroids, metabolic parameters, and genotyping. MAIN OUTCOME MEASURE(S): Associations among PCOS status, phenotype, and genetic background identified with the use of principal component analysis. RESULT(S): Principal component analysis identified five principal components (PCs). PC1 captured northwest-to-southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, and larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east-to-west European genetic variation and cholesterol levels. CONCLUSION(S): These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background. PMID- 27666563 TI - Total laparoscopic sigmoid vaginoplasty. AB - OBJECTIVE: To demonstrate step by step our technique for total laparoscopic sigmoid vaginoplasty. DESIGN: Surgical video tutorial. SETTING: Academic medical center. PATIENT(S): Transgender women with penile hypoplasia or with a failed primary vaginoplasty and biological women with either acquired or congenital absence of a functional vagina. INTERVENTION(S): An original technique for total laparoscopic sigmoid vaginoplasty is shown on video. Surgery is performed via a simultaneous abdomino-perineal approach. The genital surgeon dissects the neovaginal cavity and performs a bilateral orchiectomy and shortening of the urethra. Out of penile and scrotal skin, a clitoro-vulvaplasty is created. Meanwhile, the laparoscopic surgeon mobilizes the sigmoid segment and transects it down to the base of the sigmoid arteries. The segment is guided in an iso peristaltic way through the neovaginal tunnel on to the perineum. The distal staple line is opened and sutured in an exaggerated interdigitating fashion to the perineum and inverted penile skin. Length of the segment is measured with a transilluminated perspex dildo, after which the segment is stapled at the proper level. A neovaginopexy is performed on the promontory. Bowel continuity is restored with an intra-abdominal side-to-side oversewn stapled anastomosis. The patient provided written informed consent for the use of this video in this article. MAIN OUTCOME MEASURE(S): None. RESULT(S): Given current literature, intestinal vaginoplasty is associated with low complication rates. Since 2008 our group performed 42 primary and 21 secondary procedures, mainly in transgender women, with at least 1 year of clinical follow-up. Complications comprised three rectal perforations and two anastomotic leakages. These were addressed laparoscopically without long-term fistula formation. There were no conversions to laparotomy. CONCLUSION(S): Total laparoscopic sigmoid vaginoplasty is a feasible and safe procedure in the hands of an experienced team with the right infrastructure. It provides good surgical and functional results. In selected cases it is indicated for primary vaginoplasty, as well as for revision vaginoplasty. PMID- 27666564 TI - Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. AB - OBJECTIVE: To investigate the associations among underweight body mass index (BMI), pregnancy, and obstetric outcomes among women using assisted reproductive technology (ART). DESIGN: Retrospective cohort study using national data and log binomial regression. SETTING: Not applicable. PATIENT(S): Women undergoing IVF in the United States from 2008 to 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcomes (intrauterine pregnancy, live birth rates) per transfer, miscarriage rate per pregnancy, and low birth weight and preterm delivery rates among singleton and twin pregnancies. RESULT(S): For all fresh autologous in vitro fertilization (IVF) cycles in the United States from 2008 to 2013 (n = 494,097 cycles, n = 402,742 transfers, n = 180,855 pregnancies) reported to the national ART Surveillance System, compared with normal weight women, underweight women had a statistically significant decreased chance of intrauterine pregnancy (adjusted risk ratio [aRR] 0.97; 95% confidence interval [CI], 0.96-0.99) and live birth (aRR 0.95; 95% CI, 0.93-0.98) per transfer. Obese women also had a statistically decreased likelihood of both (aRR 0.94; 95% CI, 0.94-0.95; aRR 0.87; 95% CI, 0.86-0.88, respectively). Among cycles resulting in singleton pregnancy, both underweight and obese statuses were associated with increased risk of low birth weight (aRR 1.39; 95% CI, 1.25-1.54, aRR 1.26; 95% CI, 1.20-1.33, respectively) and preterm delivery (aRR 1.12; 95% CI, 1.01-1.23, aRR 1.42; 95% CI, 1.36-1.48, respectively). The association between underweight status and miscarriage was not statistically significant (aRR 1.04; 95% CI, 0.98 1.11). In contrast, obesity was associated with a statistically significantly increased miscarriage risk (aRR 1.23; 95% CI, 1.20-1.26). CONCLUSION(S): Among women undergoing IVF, prepregnancy BMI affects pregnancy and obstetric outcomes. Underweight status may have a limited impact on pregnancy and live-birth rates, but it is associated with increased preterm and low-birth-weight delivery risk. Obesity negatively impacts all ART and obstetric outcomes investigated. PMID- 27666566 TI - Preimplantation genetic diagnosis: why are obstetric and neonatal risks increased? The need for more data. PMID- 27666567 TI - Utilization of fertility treatment and reproductive choices by lesbian couples. AB - OBJECTIVE: To describe intentions and outcomes of lesbian couples requesting reproductive assistance; and report number of cycles needed to achieve a live birth. DESIGN: Retrospective chart review. SETTING: University-based fertility center. PATIENT(S): A total of 306 lesbian couples who sought reproductive assistance between 2004 and 2015. INTERVENTION(S): Intrauterine insemination or IVF using donor sperm. MAIN OUTCOME MEASURE(S): Mean age, relationship status, family size, preconception goals, conception attempts, number of cycles to achieve a live birth. RESULT(S): Preconception plans were available for 233 couples: 76.4% planned for one partner to conceive and carry (single partner conception); 23.6% planned for both partners to eventually conceive and carry (dual partner conception). Of 306 couples who presented, 85.1% attempted single partner conception, and 68% of these achieved a live birth. Dual partner conception was attempted by 14.9% of couples, and 88.9% achieved a live birth. Of those who conceived with IUI, a mean (+/-SD) of 3 +/- 1.1 cycles were completed. Of those who conceived with IVF, a mean of 6 +/- 1.4 IUI and 1.7 +/- 0.3 IVF cycles were completed. CONCLUSION(S): Lesbian couples may improve their likelihood of a live birth if both partners attempt conception. Further studies are needed to understand why one-fifth of patients did not pursue treatment. PMID- 27666565 TI - Female cancer survivors exposed to alkylating-agent chemotherapy have unique reproductive hormone profiles. AB - OBJECTIVE: To evaluate reproductive hormone patterns in women exposed to alkylating-agent chemotherapy. DESIGN: Prospective cohort. SETTING: University hospital. PATIENT(S): Normally menstruating mid-reproductive-age women (20-35 years old) who had previously been exposed to alkylating-agent chemotherapy for cancer treatment were compared with two healthy control populations: similarly aged women and late-reproductive-age women (43-50 years old). INTERVENTION(S): Subjects collected daily urine samples for one cycle. MAIN OUTCOME MEASURE(S): Integrated urinary pregnanediol glucuronide (PDG) and estrone conjugate (E1c) and urinary excretion of gonadotropins (FSH and LH). RESULT(S): Thirty-eight women (13 survivors, 11 same-age control subjects, 14 late-reproductive-age control subjects) provided 1,082 urine samples. Cycle length, luteal phase length, and evidence of luteal activity were similar among the groups. As expected, ovarian reserve was impaired in cancer survivors compared with same-age control subjects but similar between survivors and late-reproductive-age control subjects. In contrast, survivors had total and peak PDG levels that were similar to same-age control subjects and higher than those observed in late-reproductive-age control subjects. Survivors had higher E1c levels than both same-age and late reproductive-age control subjects. There was no difference in urinary gonadotropins among the groups. CONCLUSION(S): Women exposed to alkylating agents have a unique reproductive hormone milieu that is not solely explained by age or ovarian reserve. The urinary hormone profile observed in survivors appears more similar to same-age control subjects than to late-reproductive-age women with similar ovarian reserve, which may suggest that age plays a more important role than ovarian reserve in the follicular dynamics of survivors. PMID- 27666568 TI - Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21 expression, Akt and the Bcl-2/Bax pathway. AB - Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)-21 expression, Akt, and the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA-21, Bcl-2, Bax and phosphorylated-Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA-21 expression and phosphorylated-Akt protein expression, and reduced the Bcl-2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA-21 using anti-miR 21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA-21 serves a protective role in cardiac I/R injury via Akt and the Bcl-2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA-21 expression, Akt, and the Bcl-2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA-21 on cardiac I/R injury following treatment with trimetazidine in vivo. PMID- 27666570 TI - Corrigendum to "MK-801 reduces sensitivity to Muller-Lyer's illusion in capuchin monkeys" [Behav. Brain Res. 316 (2017) 54-58]. PMID- 27666571 TI - Lessons from 1,3-Hydride Shifts in Sesquiterpene Cyclizations. AB - Stereospecifically labelled precursors were subjected to conversion by seven bacterial sesquiterpene cyclases to investigate the stereochemistry of their initial 1,10-cyclisation-1,3-hydride shift cascades. Enzymes with products of known absolute configuration showed a coherent stereochemical course, except for (-)-alpha-amorphene synthase, for which the obtained results are better explained by an initial 1,6-cyclisation. The link between the absolute configuration of the product and the stereochemical course of the 1,3-hydride shifts enabled assignment of the absolute configurations of three enzyme products, which were confirmed independently through the absolute configuration of the common byproduct germacrene D-4-ol. PMID- 27666569 TI - Adalimumab or infliximab as monotherapy, or in combination with an immunomodulator, in the treatment of Crohn's disease. AB - BACKGROUND: The comparative efficacy of adalimumab (ADA) and infliximab (IFX) in Crohn's disease, and the benefit of initial combotherapy with an immunomodulator, are debated. AIM: To assess the best anti-TNF treatment regimens in Crohn's disease. METHODS: We included 906 biologic-naive Crohn's disease patients [median age, 31 years (24-41)] and performed a retrospective analysis of 1284 therapeutic exposures to ADA (n = 521) or IFX (n = 763) between 2006 and 2015. An immunomodulator was associated during the first 4-6 months (initial combotherapy) during 706 therapeutic exposures (55%). Median duration of anti-TNF therapy was 39 months (IQR 17-67). Primary outcomes were 6-month and 2-year response rates and drug survival. Logistic regression with propensity scoring and Cox proportional hazard analysis determined variables associated with outcomes. RESULTS: The response rates at 6 months and 2 years were 64% and 44% on ADA mono, 86% and 70% on ADA combo, 72% and 45% on IFX mono, and 84% and 68% on IFX combotherapy, respectively. Differences between ADA and IFX were not significant, whereas combotherapy was superior to monotherapy (P < 0.001). Drug survival was longer with combotherapy vs. monotherapy [adjusted hazard ratio 2.17 (1.72-2.70)] and not significantly different between ADA and IFX. During subsequent anti-TNF exposures, IFX combotherapy fared better than other groups regarding response rates, drug survival, disease activity, hospitalisations and abdominal surgery. CONCLUSION: In this retrospective analysis of a large tertiary centre cohort of Crohn's disease patients, ADA and IFX had similar efficacy as first line treatment, while initial combotherapy with an immunomodulator improved all outcome measures. PMID- 27666572 TI - Case of anal adenocarcinoma in situ with pagetoid spread but without macroscopic abnormality in anal mucosa. PMID- 27666573 TI - Haloparvum alkalitolerans sp. nov., alkali-tolerant haloarchaeon isolated from commercial salt. AB - A Gram-stain-negative, rod-pleomorphic, aerobic, halophilic archaeon, strain MK62 1T, was isolated from commercial salt made from seawater in the Philippines. Strain MK62-1T was able to grow at 2.1-4.7 M NaCl (with optimum at 2.1-2.6 M NaCl), pH 6.5-9.5 (optimum, pH 7.0-7.5) and 20-55 degrees C (optimum, 45-50 degrees C). Based on the orthologous 16S rRNA gene sequence, the closest relative was Haloparvum sedimenti JCM 30891T with 99.2 % similarity. The RNA polymerase subunit B' gene sequence also showed the highest similarity (97.4 %) to that of Haloparvum sedimenti DYS4T. The DNA G+C content of MK62-1T was 70.1 mol%, while that of Haloparvum sedimenti JCM 30891T was 69.5 mol% by the HPLC method. The levels of DNA-DNA relatedness between MK62-1T and Haloparvum sedimenti JCM 30891T were 60.6 and 60.8 % (reciprocally). The major polar lipids of the isolate were C20C20 archaeol derivatives of phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and phosphatidylglycerol sulfate. Based on the phenotypic and phylogenetic analyses, it is proposed that the isolate represents species within the genus Haloparvum, for which the name Haloparvum alkalitolerans sp. nov. is proposed. The type strain is MK62-1T (=JCM 30442T =KCTC 4214T). PMID- 27666574 TI - Abolishing the 1-year rule: How much evidence will be enough? PMID- 27666575 TI - Genome-wide nucleotide diversity of hatchery-reared Atlantic and Mediterranean strains of brown trout Salmo trutta compared to wild Mediterranean populations. AB - A genome-wide assessment of diversity is provided for wild Mediterranean brown trout Salmo trutta populations from headwater tributaries of the Orb River and from Atlantic and Mediterranean hatchery-reared strains that have been used for stocking. Double-digest restriction-site-associated DNA sequencing (dd-RADseq) was performed and the efficiency of de novo and reference-mapping approaches to obtain individual genotypes was compared. Large numbers of single nucleotide polymorphism (SNP) markers with similar genome-wide distributions were discovered using both approaches (196 639 v. 121 016 SNPs, respectively), with c. 80% of the loci detected de novo being also found with reference mapping, using the Atlantic salmon Salmo salar genome as a reference. Lower mapping density but larger nucleotide diversity (pi) was generally observed near extremities of linkage groups, consistent with regions of residual tetrasomic inheritance observed in salmonids. Genome-wide diversity estimates revealed reduced polymorphism in hatchery strains (pi = 0.0040 and pi = 0.0029 in Atlantic and Mediterranean strains, respectively) compared to wild populations (pi = 0.0049), a pattern that was congruent with allelic richness estimated from microsatellite markers. Finally, pronounced heterozygote deficiency was found in hatchery strains (Atlantic FIS = 0.18; Mediterranean FIS = 0.42), indicating that stocking practices may affect the genetic diversity in wild populations. These new genomic resources will provide important tools to define better conservation strategies in S. trutta. PMID- 27666576 TI - Pre-operative testing guidelines: a NICE try but not enough. PMID- 27666578 TI - Risk of tinnitus in patients with sleep apnea: A nationwide, population-based, case-control study. AB - OBJECTIVE: To investigate the risk of tinnitus in patients with sleep disturbance or sleep apnea. STUDY DESIGN: Case control study. METHODS: We identified 21,798 middle-aged and elderly patients with otolaryngologist-diagnosed tinnitus between January 1, 2000, and December 31, 2012, from the Longitudinal Health Insurance Database 2000 of the Taiwan National Health Insurance Research Database. A total of 108,990 controls were also identified from the same database based on frequency-matching on 10-year age interval, sex, and year of index date of the cases. Diagnoses of sleep disturbance (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 780.50, 780.52, 307.4) and sleep apnea (ICD-9-CM codes 780.51, 780.53, 780.57) in the cases and controls prior to the index date were assessed. The risks of tinnitus in patients with sleep disturbance and sleep apnea were separately evaluated with multivariate logistic regression analyses. RESULTS: The mean age of the total 130,788 patients was 59.8 years, and 47% of them were males. The risk of tinnitus was higher in patients with sleep disturbance compared to those without the condition (adjusted odds ratio [OR] = 1.13, 95% confidence interval [CI] [95% CI] = 1.11-1.17), and the risk of tinnitus was higher in patients with sleep apnea compared to those without the condition (adjusted OR = 1.36, 95% CI = 1.16-1.60). CONCLUSION: In this population-based, case-control study, the risk of tinnitus was found to be significantly higher among middle-aged and elderly Taiwanese patients with sleep disturbances, especially with sleep apnea. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:2171-2175, 2017. PMID- 27666577 TI - Quantitative diagnosis of HER2 protein expressing breast cancer by single particle quantum dot imaging. AB - Overexpression of HER2 is one of the major causes of breast cancer, and therefore precise diagnosis of its protein expression level is important. However, current methods estimating the HER2-expression level are insufficient due to problem with the lack of quantification. This might result in a gap between diagnostics and therapeutics targeting HER2. Therefore, a new effective diagnostic method is needed. We developed a new immunohistochemical (IHC) technique with quantum dots (QD)-conjugated trastuzumab using single-particle imaging to quantitatively measure the HER2 expression level. Tissues from 37 breast cancer patients with available detailed clinical information were tested by IHC with QDs (IHC-QD) and the correlation with IHC with 3,3'-diaminobenzidine (DAB), fluorescence in situ hybridization (FISH), and IHC-QD was examined. The number of QD-conjugated trastuzumab particles binding specifically to a cancer cell was precisely calculated as the IHC-QD score. The IHC-QD score in 37 cases was correlated proportionally with the score of HER2 gene copy number as assessed by FISH (R = 0.83). When HER2 positivity was judged to be positive, the IHC-QD score with our cut-off level was exactly concordant with the FISH score with a cut-off value of 2.0. Furthermore, IHC-QDs score and time to progression (TTP) of trastuzumab therapy were well correlated in HER2-positive cases (R = 0.69). Conversely, the correlation between FISH score and TTP was not observed. We developed a precisely quantitative IHC method using trastuzumab-conjugated QDs and single-particle imaging analysis and propose the possibility of using IHC-QDs score as a predictive factor for trastuzumab therapy. PMID- 27666580 TI - Elevated cerebrospinal fluid C-X-C motif chemokine 10: Commonalities in paraneoplastic neurological disorders. PMID- 27666579 TI - Heritable components of the human fecal microbiome are associated with visceral fat. AB - BACKGROUND: Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures. RESULTS: We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity. CONCLUSIONS: Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies. PMID- 27666582 TI - Introducing the concept of biocatalysis in the classroom: The conversion of cholesterol to provitamin D3. AB - Biocatalysis is a fundamental concept in biotechnology. The topic integrates knowledge of several disciplines; therefore, it was included in the course "design and optimization of biological systems" which is offered in the biochemistry curricula. We selected the ciliate tetrahymena as an example of a eukaryotic system with potential for the biotransformation of sterol metabolites of industrial interest; in particular, we focused on the conversion of cholesterol to provitamin D3. The students work with wild type and recombinant strains and learn how sterol pathways could be modified to obtain diverse sterol moieties. During the course the students identify and measure the concentration of sterols. They also search for related genes by bioinformatic analysis. Additionally, the students compare biotransformation rates, growing the ciliate in plate and in a bioreactor. Finally, they use fluorescence microscopy to localize an enzyme involved in biotransformation. The last day each team makes an oral presentation, explaining the results obtained and responds to a series of key questions posed by the teachers, which determine the final mark. In our experience, this course enables undergraduate students to become acquainted with the principles of biocatalysis as well as with standard and modern techniques, through a simple and robust laboratory exercise, using a biological system for the conversion of valuable pharmaceutical moieties. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):105-114, 2017. PMID- 27666581 TI - 4-n-butylresorcinol enhances proteolytic degradation of tyrosinase in B16F10 melanoma cells. AB - OBJECTIVE: 4-n-butylresorcinol is a competitive inhibitor of tyrosinase and has been used as an antimelanogenic agent. However, its inhibition mechanism in intact cells is not fully understood. To elucidate the cellular mechanism, we compared in vitro and in vivo inhibitory effects of 4-n-butylresorcinol on tyrosinase activity. METHODS: B16F10 melanoma cells were cultured in media containing alpha-MSH in the presence or absence of 4-n-butylresorcinol. Tyrosinase mRNA levels, protein levels and activity in B16F10 cells were compared by real-time PCR, immunostaining combined with western blot and colorimetric analysis, respectively. Melanin concentration was measured by colorimetry both in the cells and in the media. Tyrosinase glycosylation and proteolytic degradation were analysed by immunoblotting after cells were treated with Endo H/PNGase F and E64/proteasome inhibitors, respectively. RESULTS: 4-n-butylresorcinol inhibited tyrosinase activity and melanin synthesis more effectively in intact cells than in cell lysates. Western blotting and real-time RT-PCR showed that 4-n butylresorcinol reduced protein levels, but not mRNA levels, of tyrosinase in B16F10 cells. 4-n-butylresorcinol showed no effect on the processing of tyrosinase glycosylation or on trafficking to melanosomes. However, treatment of B16F10 cells with E64 or proteasome inhibitor abrogated the 4-n-butylresorcinol induced decrease of tyrosinase. Moreover, 4-n-butylresorcinol activated p38 MAPK, resulting in increased ubiquitination of tyrosinase. CONCLUSION: 4-n butylresorcinol inhibits melanogenesis by enhancing proteolytic degradation of tyrosinase as well as competitive binding to tyrosinase. These findings will help to develop new, effective and safe chemicals for the treatment of hyperpigmentation disorders. PMID- 27666583 TI - Selective Palladium-Catalyzed Aminocarbonylation of Olefins to Branched Amides. AB - A general and efficient protocol for iso-selective aminocarbonylation of olefins with aliphatic amines has been developed for the first time. Key to the success for this process is the use of a specific 2-phosphino-substituted pyrrole ligand in the presence of PdX2 (X=halide) as a pre-catalyst. Bulk industrial and functionalized olefins react with various aliphatic amines, including amino-acid derivatives, to give the corresponding branched amides generally in good yields (up to 99 %) and regioselectivities (b/l up to 99:1). PMID- 27666584 TI - Decline of cellular activation in non-B cells after rituximab treatment in hepatitis C-associated mixed cryoglobulinemia vasculitis. AB - Mixed cryoglobulinemic vasculitis is associated with the monoclonal expansion of pathognomonic B cells in chronic hepatitis C. Recently, treatment with B-cell depletion, including rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from the active disease. We investigated whether B-cell depletion therapy has an impact on activation of non-B cells in the periphery. Results demonstrated that B-cell depletion therapy is associated with a statistically significant decline in activated T cells, from pretherapy to follow up while on rituximab therapy: CD4+ CD38+ HLA-DR+ (DR+), CD8+ CD38, CD8+ CD38+ DR+, and CD8+ DR+. Birmingham Vasculitis Activity Score and cryoglobulin had a strong correlation coefficient (R) of 0.72 (P=.0005), while cryoglobulin showed moderate correlation with CD8+ DR+ (R=.61), CD3+ CD38+ DR+ (R=.57), CD3+ DR+ (R=.50), CD4+ CD38+ DR+ (R=.53), CD4+ DR+ (R=.52), and CD8+ CD38+ DR+ (R=.67). These results suggest B-cell expansion has a direct and indirect effect on the pathogenesis of Hepatitis C-associated mixed cryoglobulinemic vasculitis. PMID- 27666585 TI - Chiral Bidentate NHC Ligands Based on the 1,1'-Binaphthyl Scaffold: Synthesis and Application in Transition-Metal-Catalyzed Asymmetric Reactions. AB - The use of the chiral 1,1'-binaphthyl scaffold to construct chiral ligands can be traced back for a long time. However, the development of bidentate NHC ligands based on the same backbone has only appeared recently. In this account, we describe the design and synthesis of a new family of chiral NHC ligands based on the 1,1'-binaphthyl scaffold and demonstrate the applications of these chiral NHC metal complexes in the catalyzed oxidative kinetic resolution of secondary alcohols, asymmetric carbon-carbon bond formations, hydrosilylations, and cyclizations of 1,6-enynes. The chiral NHC ligands containing the 1,1'-binaphthyl backbone can be synthesized in good yields from enantiomerically pure 1,1' binaphthyl-2,2'-diamine. These transition metals coordinated with chiral bidentate NHC ligands exhibit high catalytic activities and good enantioselectivities for a wide range of metal-catalyzed asymmetric reactions. PMID- 27666587 TI - [Not Available]. PMID- 27666586 TI - [Not Available]. PMID- 27666588 TI - Anaphylaxis in the operating theatre. PMID- 27666589 TI - Antifungal activity of rhamnolipids against dimorphic fungi. AB - In this paper, rhamnolipids are investigated, for the first time, for their feasibility for inhibiting dimorphic fungi. Rhamnolipids were found to effectively inhibit a dimorphic fungus isolated from tomato plants which was identified as Mucor circinelloides according to characterizations by morphologies as well as 28S rDNA sequences. Rhamnolipids markedly reduced growth of this fungus in both the yeast-like form and the filamentous form. Such an inhibitive effect was similarly obtained with Verticillium dahliae, a representative member of dimorphic fungi, confirming the effectiveness of rhamnolipids in the two growth forms of dimorphic fungi. Interestingly, rhamnolipids showed a greater inhibitive function in the case of the pathogenic growth mode of dimorphic fungi, such as the mycelium growth for M. circinelloides and the yeast-like growth for V. dahliae, than their non-pathogenic modes. The use of rhamnolipids might greatly reduce the frequently-reported drugresistance to the common anti-fungal agents by deterring the possible switch between the two modes of dimorphic fungi. Overall, rhamnolipids as environment-friendly biocontrol agents have a potential use in protecting plants from dimorphic fungi infections, and could also offer guidance toward future research into controlling dimorphic disease infection in humans. PMID- 27666592 TI - FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription. AB - In eukaryotes, the packaging of genomic DNA into chromatin plays a critical role in gene regulation. However, the dynamic organization of chromatin fibers and its regulatory mechanisms remain poorly understood. Using single-molecule force spectroscopy, we reveal that the tetranucleosomes-on-a-string appears as a stable secondary structure during hierarchical organization of chromatin fibers. The stability of the tetranucleosomal unit is attenuated by histone chaperone FACT (facilitates chromatin transcription) in vitro. Consistent with in vitro observations, our genome-wide analysis further shows that FACT facilitates gene transcription by destabilizing the tetranucleosomal unit of chromatin fibers in yeast. Additionally, we found that the linker histone H1 not only enhances the stability but also facilitates the folding and unfolding kinetics of the outer nucleosomal wrap. Our study demonstrates that the tetranucleosome is a regulatory structural unit of chromatin fibers beyond the nucleosome and provides crucial mechanistic insights into the structure and dynamics of chromatin fibers during gene transcription. PMID- 27666591 TI - Ccp1 Homodimer Mediates Chromatin Integrity by Antagonizing CENP-A Loading. AB - CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here, we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner. These data indicate that factors with opposing CENP-A loading activities are recruited to centromeres. Furthermore, Ccp1 also cooperates with H2A.Z to evict CENP-A assembled in euchromatin. Structural analyses indicate that Ccp1 forms a homodimer that is required for its anti-CENP-A loading activity. Our study establishes mechanisms for maintenance of CENP-A homeostasis at centromeres and the prevention of ectopic assembly of centromeres. PMID- 27666590 TI - Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies. AB - C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB. PMID- 27666593 TI - TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses. AB - Cyclic GMP-AMP synthase (cGAS) is an essential DNA virus sensor that triggers type I interferon (IFN) signaling by producing cGAMP to initiate antiviral immunity. However, post-translational regulation of cGAS remains largely unknown. We report that K48-linked ubiquitination of cGAS is a recognition signal for p62 depdendent selective autophagic degradation. The induction of TRIM14 by type I IFN accelerates cGAS stabilization by recruiting USP14 to cleave the ubiquitin chains of cGAS at lysine (K) 414. Knockout of TRIM14 impairs herpes simplex virus type 1 (HSV-1)-triggered antiviral responses in a cGAS-dependent manner. Due to impaired type I IFN production, Trim14-/- mice are highly susceptible to lethal HSV-1 infection. Taken together, our findings reveal a positive feedback loop of cGAS signaling generated by TRIM14-USP14 and provide insights into the crosstalk between autophagy and type I IFN signaling in innate immunity. PMID- 27666595 TI - Bethesda classification is a valuable guide for fine needle aspiration reports and highly predictive especially for diagnosing aggressive variants of papillary thyroid carcinoma. AB - BACKGROUND: A fine needle aspiration biopsy (FNAB) is the most valuable diagnostic procedure for pre-operative discrimination of benign and malignant nodules. The Bethesda System for Reporting Thyroid Cytopathology provides standardised reporting and cytomorphological criteria in aspiration smears. The aim of the present study was to determine malignancy rates in nodules with different cytology results and evaluate the diagnostic value of Bethesda for variants of papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A retrospective analysis of 2534 cases with 5784 thyroid nodules, who underwent FNAB followed by surgery, were included in this study. FNAB was performed with ultrasonography guidance. Cytological diagnoses were classified as: non diagnostic (ND), benign, atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SUS) and malignant. Histopathological diagnoses were classified into four groups: benign, PTC, follicular thyroid cancer and other types of thyroid cancer (including medullary thyroid cancer, undifferentiated thyroid cancer and thyroid tumours of uncertain malignant potential). Cases with PTC were further divided into four categories: conventional variant, follicular variant, aggressive variants (tall cell, diffuse sclerosing and columnar variant) and other variants (oncocytic, solid/trabecular and warthin-like variants). FNAB results were compared with histopathological results. RESULTS: Malignancy rates were 6.3%, 3.2%, 20.7%, 33.3%, 74.2% and 95.6% in the nodules with ND, benign, AUS/FLUS, FN/SFN, SUS and malignant cytology results, respectively. Pre-operative cytology was malignant or SUS in 56.6% of conventional, 24.3% of follicular, 92% of aggressive and 41.7% of other variants of histopathologically confirmed PTC. The difference between the groups was significant (P < 0.001). CONCLUSION: The Bethesda classification is a reliable indicator of malignancy in nodules with different cytology results and seems to be very effective in predicting the malignancy for the nodules diagnosed with aggressive variant PTC on the final histological examination. PMID- 27666597 TI - Glutamate Promotes Contraction of the Rat Ductus Arteriosus. AB - BACKGROUND: Extremely preterm infants frequently have patent ductus arteriosus (PDA). Recent recommendations include immediately beginning amino acid supplementation in extremely preterm infants. However, the effect of amino acids on closure of the ductus arteriosus (DA) remains unknown.Methods and Results:Aminogram results in human neonates at day 2 revealed that the plasma glutamate concentration was significantly lower in extremely preterm infants (<28 weeks' gestation) with PDA than in those without PDA and relatively mature preterm infants (28-29 weeks gestation). To investigate the effect of glutamate on DA closure, glutamate receptor expression in fetal rats was examined and it was found that the glutamate inotropic receptor, alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionate (AMPA) type subunit 1 (GluR1), mRNA was highly expressed in the DA compared to the aorta on gestational day 19 (preterm) and gestational day 21 (term). GluR1 proteins were co-localized with tyrosine hydroxylase-positive autonomic nerve terminals in the rat and human DA. Intraperitoneal administration of glutamate increased noradrenaline production in the rat DA. A whole-body freezing method demonstrated that glutamate administration induced DA contraction in both preterm (gestational day 20) and term rat fetuses. Glutamate-induced DA contraction was attenuated by the calcium-sensitive GluR receptor antagonist, NASPM, or the adrenergic receptor alpha1 blocker, prazosin. CONCLUSIONS: These data suggest that glutamate induces DA contraction through GluR-mediated noradrenaline production. Supplementation of glutamate might help to prevent PDA in extremely preterm infants. (Circ J 2016; 80: 2388-2396). PMID- 27666598 TI - Calcium-Channel Blockers and Dementia Risk in Older Adults - National Health Insurance Service - Senior Cohort (2002-2013). AB - BACKGROUND: Some disagreements surround the effects of calcium-channel blockers (CCBs) on the risk of dementia. The purpose of this study was to investigate the protective effects of CCBs on dementia among elderly hypertensive Koreans.Methods and Results:We conducted a large population-based cohort study using the senior cohort database of the Korean National Health Insurance Service (2002-2013). Subjects were elderly hypertensive Koreans older than 60 years of age. A total of 18,423 patients (CCB user group: 13,692 patients; non-CCB antihypertensive user group: 4,731 patients) were statistically analyzed using the Cox proportional hazard regression model to estimate the adjusted hazard ratio (aHR) and confidence intervals (CIs) of dementia associated with CCB use. There were 2,881 cases (21.0%) of dementia in the CCB user group and 1,124 cases (23.8%) in the non-user group. CCB use significantly reduced the risk of total dementia (aHR 0.81, 95% CI 0.75-0.87, P<0.0001), Alzheimer's dementia (aHR 0.80, 95% CI 0.72 0.88, P<0.0001), and vascular dementia (aHR 0.81, 95% CI 0.70-0.94, P=0.0067). CONCLUSIONS: CCB use had a protective effect on the risk of dementia among elderly hypertensive Koreans. (Circ J 2016; 80: 2336-2342). PMID- 27666594 TI - Bromodomain Inhibitors Correct Bioenergetic Deficiency Caused by Mitochondrial Disease Complex I Mutations. AB - Mitochondrial diseases comprise a heterogeneous group of genetically inherited disorders that cause failures in energetic and metabolic function. Boosting residual oxidative phosphorylation (OXPHOS) activity can partially correct these failures. Herein, using a high-throughput chemical screen, we identified the bromodomain inhibitor I-BET 525762A as one of the top hits that increases COX5a protein levels in complex I (CI) mutant cybrid cells. In parallel, bromodomain containing protein 4 (BRD4), a target of I-BET 525762A, was identified using a genome-wide CRISPR screen to search for genes whose loss of function rescues death of CI-impaired cybrids grown under conditions requiring OXPHOS activity for survival. We show that I-BET525762A or loss of BRD4 remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by mutations or chemical inhibition of CI. These studies show that BRD4 inhibition may have therapeutic implications for the treatment of mitochondrial diseases. PMID- 27666599 TI - Prevalence and Distribution of Coronary Artery Calcification in Asymptomatic United States and Korean Adults - Cross-Sectional Propensity-Matched Analysis. AB - BACKGROUND: The incidence of coronary artery disease (CAD) varies depending on ethnicity, but the precise differences remain to be firmly established. This study therefore evaluated the disparity in coronary artery calcification (CAC), as a marker of CAD, in asymptomatic US and Korean adults.Methods and Results:CAC score was compared between asymptomatic Korean (n=15,128) and US (n=7,533) adults. Propensity score matching was performed according to age, gender, hypertension, diabetes, dyslipidemia, and current smoking, which generated 2 cohorts of 5,427 matched pairs. Both cohorts were categorized according to age group: 45-54, 55-64, and 65-74 years. Overall, the prevalence of CAC score >0, >100, and >400 in Korean adults was lower than in US adults (P<0.001, all). According to increasing age groups, the likelihood of CAC was most often lower in Korean adults, especially in Korean women. The odds of having CAC >400 in Korean adults aged 65-74 years was 0.66 (95% CI: 0.48-0.91) overall, 0.78 (95% CI: 0.52 1.19) in men, and 0.50 (95% CI: 0.29-0.86) in women, compared with US counterparts. CONCLUSIONS: Korean adults have a lower prevalence and severity of atherosclerotic burden as assessed on CAC, compared with US adults, but the disparity in CAC according to ethnicity may decline with older age. (Circ J 2016; 80: 2349-2355). PMID- 27666600 TI - Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression. AB - Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2MUg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of salinomycin. A combination of cisplatin and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-AKT, and TS expression. Overexpression of a constitutive active AKT (AKT-CA) expression vector reversed the salinomycin and cisplatin-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in salinomycin and cisplatin cotreated cells. Our findings suggested that the down regulation of AKT-mediated TS expression by salinomycin enhanced the cisplatin induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with cisplatin for lung cancer treatment. PMID- 27666602 TI - [Retracted] Slit-miR-218-Robo axis regulates retinal neovascularization. AB - Following the publication of this article, it was brought to our attention that five of the Figures contained in this study were published entirely, or in part, in the following publication, on which several of us were co-authors: Han S, Kong YC, Sun B, Han QH, Chen Y and Wang YC: microRNA-218 inhibits oxygen-induced retinal neovascularization via reducing the expression of roundabout 1. Chin Med J (Engl) 129: 709-715, 2016. While we had intended that these papers offered different research perspectives, we were reminded of the fact that, in submitting the article to International Journal of Molecular Medicine, the work described therein was required to be "original research that has not been published previously, and is not under consideration for publication elsewhere, in whole or in part". Therefore, owing to the redundancy in the data between these publications, the above paper is to be retracted. All the authors have agreed to the retraction. We sincerely apologize for our misunderstanding, and deeply regret any inconvenience this mistake has caused.[the original article was published in the International Journal of Molecular Medicine 37: 1139-1145, 2016; DOI: 10.3892/ijmm.2016.2511]. PMID- 27666601 TI - Allosteric activation of midazolam CYP3A5 hydroxylase activity by icotinib - Enhancement by ketoconazole. AB - Icotinib (ICO), a novel small molecule and a tyrosine kinase inhibitor, was developed and approved recently in China for non-small cell lung cancer. During screening for CYP inhibition potential in human liver microsomes (HLM), heterotropic activation toward CYP3A5 was revealed. Activation by icotinib was observed with CYP3A-mediated midazolam hydroxylase activity in HLM (~40% over the baseline) or recombinant human CYP3A5 (rhCYP3A5) (~70% over the baseline), but not in the other major CYPs including rhCYP3A4. When co-incubated with selective CYP3A4 inhibitor CYP3cide or monoclonal human CYP3A4 inhibitory antibody in HLM, the activation was extended to ~60%, suggesting CYP3A5 might be the isozyme involved. Further, the relative activation was enhanced to ~270% in rhCYP3A5 in the presence of ketoconazole. The activation was substrate and pathway dependent and observed only in the formation of 1'-OH-midazolam, and not 4-OH-midazolam, 6beta-OH-testosterone, or oxidized nifedipine. The activation requires the presence of cytochrome b5 and it is only observed in the liver microsomes of dogs, monkeys, and humans, but not in rats and mice. Kinetic analyses of 1'-OH midazolam formation showed that ICO increased the Vmax values in HLM and rhCYP3A5 with no significant changes in Km values. By adding CYP3cide with ICO to the incubation, the Vmax values increased 2-fold over the CYP3cide control. Addition of ketoconazole with ICO alone or ICO plus CYP3cide resulted in an increase in Vmax values and decrease in Km values compared to their controls. This phenomenon may be attributed to a new mechanism of CYP3A5 heterotropic activation, which warrants further investigation. PMID- 27666603 TI - The effect of increased body mass index on patient dose in paediatric radiography. AB - Radiation protection is of particular importance in paediatric radiology. In this study, the influence of increased body mass index (BMI) in radiation dose and associated risk was investigated for paediatric patients aged 5-6.5 years, undergoing chest (64 patients) or abdomen (64 patients) radiography. Patients were categorized into normal and overweight, according to the BMI classification scheme. Entrance surface dose (ESD), organ dose, effective dose (ED) and risk of exposure induced cancer death (REID) were calculated using the Monte Carlo based code PCXMC 2.0. Statistically significant increase in patient radiation dose and REID was obtained for overweight patients as compared to normal ones, in both chest and abdomen examinations (Wilcoxon singed-rank test for paired data, p<0.001). The percentage increase in overweight as compared to normal patients of ESD, organ dose (maximum value), ED and REID was 13.6%, 24.4%, 18.9% and 20.6%, respectively, in case of chest radiographs. Corresponding values in case of abdomen radiographs were 15.0%, 24.7%, 21.8% and 19.8%, respectively. An increased BMI results in increased patient radiation dose in chest and abdomen paediatric radiography. PMID- 27666604 TI - Intestinal malrotation in patients with situs anomaly: Implication of the relative positions of the superior mesenteric artery and vein. AB - PURPOSE: To assess the usefulness of the relative position of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) in diagnosing intestinal malrotation in situs anomaly. MATERIALS AND METHODS: From January 2004 to April 2015, 33 patients with situs anomalies were enrolled in this study who underwent abdominal USG, CT or MRI as well as upper gastrointestinal series (UGIS) or surgery: situs inversus (n=16), left isomerism (n=10), and right isomerism (n=7); age 21.2+/-23.2years (mean+/-standard deviation), range 0-72 years. The intestinal malrotation was confirmed with UGIS and/or operation in 16 patients. Relative positions of the SMV to the SMA were classified into four groups by reviewing abdominal USG, CT, or MRI: right sided, left sided, ventral sided, and dorsal sided. The incidence of malrotation was analyzed for each group. RESULTS: In 16 patients with situs inversus, there was reversed SMA-SMV relationship: left sided (n=11) or ventral sided (n=5). One situs inversus patient with ventral sided SMV had intestinal malrotation (6.25%). 17 patients with situs ambiguus showed various SMA-SMV relationships (ventral sided, n=7; left sided, n=5; right sided, n=4; dorsal sided, n=1). Among them, 15 patients (88.2%) had intestinal malrotation. Two patients with normal rotation had either right sided or dorsal sided SMV. CONCLUSION: Situs ambiguus was commonly associated with intestinal malrotation with a variable SMA-SMV relationship. Reversal of the mesenteric vascular relationship was observed in situs inversus with normal rotation, not excluding the possibility of intestinal malrotation. PMID- 27666605 TI - Predictive values of BI-RADS((r)) magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS). AB - PURPOSE: The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. MATERIALS AND METHODS: Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. RESULTS: Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. CONCLUSION: BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases. PMID- 27666606 TI - Thin-section computed tomography-histopathologic comparisons of pulmonary focal interstitial fibrosis, atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma with pure ground-glass opacity. AB - OBJECTIVE: To retrospectively compare focal interstitial fibrosis (FIF), atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) with pure ground-glass opacity (GGO) using thin section computed tomography (CT). MATERIALS AND METHODS: Sixty pathologically confirmed cases were reviewed including 7 cases of FIF, 17 of AAH, 23of AIS, and 13 of MIA. All nodules kept pure ground glass appearances before surgical resection and their last time of thin-section CT imaging data before operation were collected. Differences of patient demographics and CT features were compared among these four types of lesions. RESULTS: FIF occurred more frequently in males and smokers while the others occurred more frequently in female nonsmokers. Nodule size was significant larger in MIA (P<0.001, cut-off value=7.5mm). Nodule shape (P=0.045), margin characteristics (P<0.001), the presence of pleural indentation (P=0.032), and vascular ingress (P<0.001) were significant factors that differentiated the 4 groups. A concave margin was only demonstrated in a high proportion of FIF at 85.7% (P=0.002). There were no significant differences (all P>0.05) in age, malignant history, attenuation value, location, and presence of bubble-like lucency. CONCLUSION: A nodule size >7.5mm increases the possibility of MIA. A concave margin could be useful for differentiation of FIF from the other malignant or pre-malignant GGO nodules. The presence of spiculation or pleural indentation may preclude the diagnosis of AAH. PMID- 27666607 TI - Measurement of skeletal muscle area: Comparison of CT and MR imaging. AB - OBJECTIVE: To investigate the intra- and inter-observer agreement and correlation between CT and MR measurements of skeletal muscle area (SMA) in the abdomen. METHODS: CT and MR images from twelve patients were analyzed by two blinded observers using segmentation software (MITK-3M3, Mint Medical and Slice-O-Matic, Tomovision) to quantify SMA. MR images included T1w "in-phase", T1w "out-of phase", and T2w sequences. Inter- and intra-observer agreement was assessed using the intraclass correlation coefficient (ICC). Pearson correlation coefficient (r) was used to correlate measurements obtained on MR with CT. CT and MR measurements were compared with Bland-Altman plots. RESULTS: Intra- and inter-observer agreement for SMA was high for CT and MR. For MR, the measurements on T2w images showed the highest inter-observer agreement (ICC=0.96). CT SMA correlated closely with MR, with T2w images showing the highest correlation (r=0.98; P<0.01). Bland Altman plots showed a 1.7%-3.9% bias between CT and MR measurements, lowest for T2w images. CONCLUSIONS: MR SMA measurements are reproducible and correlate closely with CT. The T2w sequence is recommended to quantify SMA on MR images. PMID- 27666608 TI - Utility of dynamic contrast-enhanced magnetic resonance imaging for differentiating glioblastoma, primary central nervous system lymphoma and brain metastatic tumor. AB - PURPOSE: The study aimed to investigate the use of dynamic contrast-enhanced magnetic resonance imaging (MRI)-derived permeability parameters for the differentiation of glioblastoma multiformes (GBMs), primary central nervous system lymphomas (PCNSLs), and brain metastatic tumors (MTs). MATERIALS AND METHODS: Seventy-five patients with histopathologically confirmed GBMs (n=38), PCNSLs (n=16) and MTs (n=21) underwent dynamic contrast-enhanced MRIs before surgery. The volume transfer constant K(trans), the flux rate constant between extravascular extracellular space and plasma Kep, the extravascular extracellular volume Ve and the fractional plasma volume Vp were measured within the entire contrast-enhancing tumor by extended Tofts model. A one-way analysis of variance was used to compare all of the parameters among these three tumors, followed by the post-hoc test. Receiver operating characteristic curves were constructed to evaluate the diagnostic performance of the permeability parameters. RESULTS: Mean K(trans) value and Ve value were significantly higher in PCNSLs than in GBMs (P<0.001 and P=0.011) and MTs (P<0.001 and P<0.001). No significant difference was observed in all of the permeability parameters between GBMs and MTs. According to the receiver operating characteristic analyses, both K(trans) and Ve had good diagnostic performance for discriminating between PCNSLs and GBMs (the area under the curve: 0.847 and 0.785, respectively), as well as between PCNSLs and MTs (the area under the curve: 0.851 and 0.884, respectively). CONCLUSIONS: The K(trans) and Ve derived from dynamic contrast-enhanced MRI facilitate the differentiation of PCNSLs from GBMs and MTs. PMID- 27666609 TI - Computer-aided diagnosis (CAD) of subsolid nodules: Evaluation of a commercial CAD system. AB - OBJECTIVES: To evaluate the performance of a commercially available CAD system for automated detection and measurement of subsolid nodules. MATERIALS AND METHODS: The CAD system was tested on 50 pure ground-glass and 50 part-solid nodules (median diameter: 17mm) previously found on standard-dose CT scans in 100 different patients. True nodule detection and the total number of CAD marks were evaluated at different sensitivity settings. The influence of nodule and CT acquisition characteristics was analyzed with logistic regression. Software and manually measured diameters were compared with Spearman and Bland-Altman methods. RESULTS: With sensitivity adjusted for 3-mm nodule detection, 50/100 (50%) subsolid nodules were detected, at the average cost of 17 CAD marks per CT. These figures were respectively 26/100 (26%) and 2 at the 5-mm setting. At the highest sensitivity setting (2-mm nodule detection), the average number of CAD marks per CT was 41 but the nodule detection rate only increased to 54%. Part-solid nodules were better detected than pure ground glass nodules: 36/50 (72%) versus 14/50 (28%) at the 3-mm setting (p<0.0001), with no influence of the solid component size. Except for the type (i.e. part solid or pure ground glass), no other nodule characteristic influenced the detection rate. High-quality segmentation was obtained for 79 nodules, which for automated measurements correlated well with manual measurements (rho=0.90[0.84-0.93]). All part-solid nodules had software measured attenuation values above -671Hounsfield units (HU). CONCLUSION: The detection rate of subsolid nodules by this CAD system was insufficient, but high quality segmentation was obtained in 79% of cases, allowing automated measurement of size and attenuation. PMID- 27666610 TI - Efficacy of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) for shoulder magnetic resonance (MR) imaging. AB - OBJECTIVES: To elucidate the utility of PROPELLER for motion artefact reduction on shoulder MRI and to examine the influence of streak artefacts on diagnosis of clinical images. METHODS: 15 healthy volunteers and 48 patients underwent shoulder MRI with/without PROPELLER (coronal oblique proton density-fast spin echo [PD-FSE], sagittal oblique T2-FSE). In a volunteer study, all sequences were performed in both static and exercise-loaded conditions. Two radiologists graded artefacts and delineation of various anatomical structures in the volunteer study and motion and streak artefacts in the clinical study. Mean scores were compared between sequences with/without PROPELLER. In the clinical study, mean scores of motion artefacts were compared with mean scores of streak artefacts. Wilcoxon signed-rank test was used for all comparisons. RESULTS: In both studies, PROPELLER significantly reduced motion artefacts (P<0.05). In the volunteer study, it significantly improved delineations in sagittal oblique images in the exercise-loaded condition (P<0.05). In the clinical study, streak artefacts appeared dominantly on images with PROPELLER (P<0.05), but influenced diagnosis to a lesser extent than motion artefacts. CONCLUSION: PROPELLER can reduce motion artefacts in shoulder MRI. While it does cause streak artefacts, it affects diagnosis to a lesser extent. PMID- 27666611 TI - Limited diagnostic value of Dual-Time-Point (18)F-FDG PET/CT imaging for classifying solitary pulmonary nodules in granuloma-endemic regions both at visual and quantitative analyses. AB - PURPOSE: This study is aimed to compare the diagnostic power of using quantitative analysis or visual analysis with single time point imaging (STPI) PET/CT and dual time point imaging (DTPI) PET/CT for the classification of solitary pulmonary nodules (SPN) lesions in granuloma-endemic regions. METHODS: SPN patients who received early and delayed (18)F-FDG PET/CT at 60min and 180min post-injection were retrospectively reviewed. Diagnoses are confirmed by pathological results or follow-ups. Three quantitative metrics, early SUVmax, delayed SUVmax and retention index(the percentage changes between the early SUVmax and delayed SUVmax), were measured for each lesion. Three 5-point scale score was given by blinded interpretations performed by physicians based on STPI PET/CT images, DTPI PET/CT images and CT images, respectively. ROC analysis was performed on three quantitative metrics and three visual interpretation scores. RESULT: One-hundred-forty-nine patients were retrospectively included. The areas under curve (AUC) of the ROC curves of early SUVmax, delayed SUVmax, RI, STPI PET/CT score, DTPI PET/CT score and CT score are 0.73, 0.74, 0.61, 0.77 0.75 and 0.76, respectively. There were no significant differences between the AUCs in visual interpretation of STPI PET/CT images and DTPI PET/CT images, nor in early SUVmax and delayed SUVmax. The differences of sensitivity, specificity and accuracy between STPI PET/CT and DTPI PET/CT were not significantly different in either quantitative analysis or visual interpretation. CONCLUSION: In granuloma endemic regions, DTPI PET/CT did not offer significant improvement over STPI PET/CT in differentiating malignant SPNs in both quantitative analysis and visual interpretation. PMID- 27666614 TI - Differentiation of benign and malignant lung lesions: Dual-Energy Computed Tomography findings. AB - PURPOSE: To determine whether parameters generated by Dual-Energy Computed Tomography (DECT) can distinguish malignant from benign lung lesions. METHODS: A prospective review of 125 patients with 126 lung lesions (23 benign and 103 malignant) who underwent lung DECT during arterial phase. All lesions were confirmed by tissue sampling. A radiologist semi-automatically contoured lesions and placed regions of interest (ROIs) in paravertebral muscle (PVM) for normalization. Variables related to absorption in Hounsfield units (HU), effective atomic number (Zeff), iodine concentration (rhoI) and spectral CT curves were assessed. Receiver operating characteristic (ROC) curves were generated to calculate sensitivity and specificity as predictors of malignancy. Multivariate logistic regression analysis was performed. RESULTS: Reproducibility of measures normalized with PVM was poor. Bivariate analysis showed minimum Zeff and normalized mean Zeff to be statistically significant (p=0.001), with area under the curve (AUC) values: 0.66 (CI 95% 0.54-0.80) and 0.72 (CI 95%, 0.60 0.84), respectively. Logistic regression models showed no differences between raw and normalized measurements. In both models, minimum HU (OR: 0.9) and size (OR: 0.1) were predictive of benign lesions. CONCLUSIONS: A quantitative approach to DECT using raw measurements is simpler than logistic regression models. Normalization to PVM was not clinically reliable due to its poor reproducibility. Further studies are needed to confirm our findings. PMID- 27666613 TI - Knowledge-based iterative model reconstruction technique in computed tomography of lumbar spine lowers radiation dose and improves tissue differentiation for patients with lower back pain. AB - PURPOSE: To evaluate the image quality and diagnostic confidence of reduced-dose computed tomography (CT) of the lumbar spine (L-spine) reconstructed with knowledge-based iterative model reconstruction (IMR). MATERIALS AND METHODS: Prospectively, group A consisted of 55 patients imaged with standard acquisition reconstructed with filtered back-projection. Group B consisted of 58 patients imaged with half tube current, reconstructed with hybrid iterative reconstruction (iDose(4)) in Group B1 and knowledge-based IMR in Group B2. Signal-to-noise ratio (SNR) of different regions, the contrast-to-noise ratio between the intervetebral disc (IVD) and dural sac (D-D CNR), and subjective image quality of different regions were compared. Higher strength IMR was also compared in spinal stenosis cases. RESULTS: The SNR of the psoas muscle and D-D CNR were significantly higher in the IMR group. Except for the facet joint, subjective image quality of other regions including IVD, intervertebral foramen (IVF), dural sac, peridural fat, ligmentum flavum, and overall diagnostic acceptability were best for the IMR group. Diagnostic confidence of narrowing IVF and IVD was good (kappa=0.58-0.85). Higher strength IMR delineated IVD better in spinal stenosis cases. CONCLUSION: Lower dose CT of L-spine reconstructed with IMR demonstrates better tissue differentiation than iDose(4) and standard dose CT with FBP. PMID- 27666615 TI - Renal zoomed EPI-DWI with spatially-selective radiofrequency excitation pulses in two dimensions. AB - PURPOSE: To evaluate the feasibility and clinical robustness of zoomed diffusion weighted echo planar imaging (z-EPI) relative to conventional single-shot EPI (c EPI) for DWI of the kidneys. MATERIALS AND METHODS: This retrospective study was approved by the institutional research ethics board. 66 patients (median age 58.5 years+/-13.4, range 23-83 years, 45 men, 21 women) undergoing 3T (Magnetom Skyra((r)), Siemens Healthcare, Erlangen, Germany) using a dynamic parallel transmit array (TimTX TrueShape, Siemens Healthcare, Erlangen, Germany) for renal MRI were included in this study. Both c-EPI and z-EPI images were obtained. For z EPI, a two-dimensional spatially-selective radiofrequency (RF) pulse was applied for echo planar imaging with the FOV reduced by a factor of 3. Two radiologists, blinded to clinical data and scan parameters evaluated the images with respect to their diagnostic confidence, overall preference, overall image quality, delineation of the kidney, spatial distortion, and image blur. Sequences were compared using a paired Wilcoxon test. ADC values for the upper pole, mid-zone, lower pole of the normal kidneys were compared between sequences as well as ADC values for renal lesions, using a paired t-test. RESULTS: With z-EPI, the kidney was significantly better delineated with sharper boundaries, less image blur and distortion, and overall better image quality relative to c-EPI (all p<0.001). The z-EPI technique led to greater diagnostic confidence than c-EPI (p=0.020). z-EPI was preferred to c-EPI in 60 cases (90.9%, 60/66). No statistically significant differences in the ADC values of renal parenchyma or of renal lesions were observed between the two sequences (all p>0.05). CONCLUSION: Image quality, distortion, and susceptibility artifacts might be improved by using z-EPI rather than c-EPI for DWI of the kidney. PMID- 27666616 TI - Diagnostic performance of power doppler and ultrasound contrast agents in early imaging-based diagnosis of organ-confined prostate cancer: Is it possible to spare cores with contrast-guided biopsy? AB - OBJECTIVES: To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS. MATERIAL AND METHODS: A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4-20ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS targeted (SonoVue) 2-core biopsies. RESULTS: Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3+/-7.01years (95% CI, 63.75 64.70); mean total PSA was 8.9+/-3.61ng/mL (95% CI, 8.67-9.13) and the mean prostate volume was 56.2+/-29cc (95% CI, 54.2-58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16% vs. 35%), and stage cT2 (43.5% vs. 66.6%), with a p value<0.05. Following the "core-by-core" analysis, the detection rates by core of CEUS targeted biopsy versus randomized biopsy were: Global population (16% vs. 13%), stage cT1 (30.3% vs. 28%), and stage cT2 (48% vs. 37%), with a p value>0.05. The NNT for CEUS-targeted biopsy was 83.3. CONCLUSIONS: The low sensitivity, specificity, positive predictive and negative predictive values of gray scale-B mode, PDUS and CEUS represent scant diagnostic performance of these variables in prostate cancer detection. Prostate cancer detection rates yielded by randomized biopsy were superior than the detection rate of targeted biopsy using B-mode, PDUS and CEUS; as a result, randomized biopsy versus CEUS-targeted biopsies cannot be excluded from biopsy strategy plans for the diagnosis of prostate cancer. PMID- 27666612 TI - Clinical evaluation vs magnetic resonance imaging of the skier's thumb: A prospective cohort of 30 patients. AB - INTRODUCTION: A skiers thumb, or a partial or complete rupture of the ulnar collateral ligament (UCL) is a clinical diagnosis. Swelling, pain, natural left right difference and inexperience of a young physician can cause difficulty to correctly diagnose this injury. However, our theory is that any physician, given the correct instructions, should be able to diagnose this injury solely on clinical findings, without the necessity of additional imaging. MATERIAL AND METHODS: In a large Dutch teaching hospital, physicians (residents with working experience of 6months-3years) working at the ER received instructions for physical examination. Patients >18 years, with an injury <1 week old, suspected of a true skier's thumb had an MRI reported by two independent radiologists to confirm the diagnosis. RESULTS: Thirty patients were included. Seven patients had no fixed endpoint (23%), all had a complete ligamentous rupture of the UCL on MRI, of which three patients had a Stener lesion. Fifteen patients (50%) met with the criteria >35 degrees laxity in extension of MCP/ >20 degrees laxity in 30 degrees flexion of the MCP. Of these, thirteen patients (81%) had a complete rupture (nine Stener lesions (56%)). One patient had a partial injury and one patient had no UCL-injury. Eight patients (27%) had inconclusive results during physical examination. Of these, two had a complete rupture (40%, 1 Stener). Three patients had a partial rupture and three patients had an intact UCL. CONCLUSION: A skier's thumb can be diagnosed by any resident when correctly instructed. Additional imaging when diagnosing a skier's thumb should be reserved in cases when physical examination remains inconclusive. PMID- 27666617 TI - Magnetic resonance imaging in the preoperative setting for breast cancer patients with undetected additional disease. AB - OBJECTIVE: The last few years have witnessed a significant increase in the preoperative use of Magnetic Resonance Imaging (MRI) for staging purposes in breast cancer (BC) patients. Many studies have confirmed the improvement that MRI can provide in terms of diagnostic assessment, especially with regard to additional disease foci. In the present study, we address the advantages and disadvantages of MRI in the preoperative setting for BC patients. PATIENTS AND METHODS: There were 1513 consecutive breast MRI studies performed in patients with either primary or recurrent BC, who were scheduled for surgery. RESULTS: Beyond the primary lesion, 10.4% of our cases had additional disease at the final histological assessment. MRI overall sensitivity, when considering tumour size and additional foci together, was 74.3%, and 80.3% when considering additional foci exclusively. MRI specificity for additional disease was 95.3%, positive predictive value was 77.4%, and negative predictive value was 94.6%. Nevertheless, 5% of cases had additional tumours that were missed by MRI or, conversely, had additional foci on MRI that were not confirmed by histology. Age (p=0.020) and lobular carcinomas (p=0.030) showed significance in the multivariate analysis by logistic regression, using the presence of additional foci diagnosed by MRI as a dependent variable. CONCLUSION: Preoperative MRI seems to have a role in preoperative tumour staging for breast cancer patients, as it discloses additional disease foci in some patients, including contralateral involvement. However, given the lack of absolute accuracy, core-needle biopsy cannot be neglected in the diagnosis of such additional malignant foci, which could result in a change in surgical treatment. PMID- 27666618 TI - Mean diffusivity discriminates between prostate cancer with grade group 1&2 and grade groups equal to or greater than 3. AB - PURPOSE: To test the potential ability of mean diffusivity (MD) and fractional anisotropy (FA) in discriminating between PCa of grade group (GG) 1&2, and GGs>=3. MATERIAL AND METHODS: Diffusion Tensor Imaging (DTI) experiments at 3T in a cohort of 38 patients with PCa (fifty lesions in total) were performed, by using different diffusion weights (b values) up to 2500s/mm(2). Gleason score (GS) and GG data were correlated with DTI parameters (MD and FA) estimated in PCa. The relation between DTI measures and GS was tested by the linear correlation analysis (Pearson's coefficient). One-way analysis of variance to check the statistical significance of the difference between GG 1&2 and GGs 3, 4, 5, >=3 was used. Results were reported for each of the three b-values ranges: 0 800s/mm(2), 0-1500s/mm(2), 0-2500s/mm(2). RESULTS: A negative correlation was found between MD and GS. The highest linear correlation was observed when the fit was performed with data acquired in the b-values range 0-2500s/mm(2). MD values were significantly different between GG 1&2 and GG=3 and between GG 1&2 and GG >=3. Moreover this difference is better defined when high b values (higher than b=800s/mm(2)) are used. The specificity, sensitivity and accuracy in the discrimination between GG 1&2 and GG=3 were: 90%, 66.7% and 82.4%, respectively when MD was estimated in the b-values range 0-2500s/mm(2) while these values were 85%, 58.3% and 78.4% when MD was estimated in the b-values range 0-800s/mm(2). Conversely FA did not discriminate between GG 1&2 and GG >=3, at any investigated b-values range. CONCLUSION: This study suggests that MD estimation in PCa, obtained from DTI acquired at high b-values, can contribute to the diagnosis and grading of prostate cancer while FA is not a useful parameter for this purpose. PMID- 27666619 TI - Radiology heads the top fifty publishing specialties over seven decades. PMID- 27666621 TI - Heart deformation analysis for automated quantification of cardiac function and regional myocardial motion patterns: A proof of concept study in patients with cardiomyopathy and healthy subjects. AB - OBJECTIVE: To test the performance of HDA in characterizing left ventricular (LV) function and regional myocardial motion patterns in the context of cardiomyopathy based on cine cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: Following the approval of the institutional review board (IRB), standard cine images of 45 subjects, including 15 healthy volunteers, 15 patients with hypertrophic cardiomyopathy (HCM) and 15 patients with dilated cardiomyopathy (DCM) were retrospectively analyzed using HDA. The variations of LV ejection fraction (LVEF), LV mass (LVM), and regional myocardial motion indices, including radial (Drr), circumferential (Dcc) displacement, radial (Vrr) and circumferential (Vcc) velocity, radial (Err), circumferential (Ecc) and shear (Ess) strain and radial (SRr) and circumferential (SRc) strain rate, were calculated and compared among subject groups. Inter-study reproducibility of HDA derived myocardial motion indices were tested on 15 volunteers by using intra class correlation coefficient (ICC) and coefficient of variation (CoV). RESULTS: HDA identified significant differences in cardiac function and motion indices between subject groups. DCM patients had significantly lower LVEF (33.5+/-9.65%), LVM (105.88+/-21.93g), peak Drr (0.29+/-0.11cm), Vrr-sys (2.14+/-0.72cm/s), Err (0.17+/-0.08), Ecc (-0.08+/-0.03), SRr-sys (0.91+/-0.44s(-1)) and SRc-sys ( 0.64+/-0.27s(-1)) compared to the other two groups. HCM patients demonstrated increased LVM (171.69+/-34.19) and lower peak Vcc-dia (0.78+/-0.30cm/s) than other subjects. Good inter-study reproducibility was found for all HDA-derived myocardial indices in healthy volunteers (ICC=0.664-0.942, CoV=15.1%-37.1%). CONCLUSION: Without the need for operator interaction, HDA is a reproducible method for the automated characterization of global and regional LV function in the context of cardiomyopathy. PMID- 27666620 TI - The correlation between FDG uptake and biological molecular markers in pancreatic cancer patients. AB - PURPOSE: We examined whether fluorine-18 fluorodeoxyglucose (FDG) uptake is related to the mammalian target of rapamycin (mTOR) signal pathway and its related proteins in pancreatic cancer patients. METHODS: We retrospectively studied 53 pancreatic cancer patients who underwent FDG positron emission tomography (PET) or FDG PET/CT, and complete curative surgical resection. The SUV max, the tumor to nontumor activity of pancreas [T/N (P)] ratio and the T/N of liver [T/N (L)] ratio were calculated. The expressions of glucose transporter 1(Glut-1) and mTOR pathway proteins in pancreas cell lines were examined by immune blots. Excised tumor tissue was analyzed by immunohistochemistry using monoclonal antibodies for Glut-1, epidermal growth factor receptor (EGFR), mTOR, p70S6kinase (p70S6) and S6 ribosomal protein (S6). RESULTS: The expressions of Glut-1, EGFR and p70S6 were significantly correlated with the SUV max, T/N (P) ratio and T/N (L) ratio. The expressions of mTOR and S6 were not correlated with all parameters. The expression of Glut-1 was positively correlated with the expressions of EGFR and p70S6, but not with mTOR or S6. S6 was positively correlated with p70S6. CONCLUSIONS: Glut-1, EGFR and p70S6 expressions are associated with the FDG uptake mechanism of pancreatic cancer. FDG uptake may predict the levels of EGFR and p70S6 expressions, and FDG uptake reflects glucose metabolism and cancer progression. PMID- 27666622 TI - Readout-segmented echo-planar imaging improves the image quality of diffusion weighted MR imaging in rectal cancer: Comparison with single-shot echo-planar diffusion-weighted sequences. AB - PURPOSE: To determine whether readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted imaging (DWI) can improve the image quality in patients with rectal cancer compared with single-shot echo-planar imaging (ss-EPI) DWI using 3.0 T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the Institutional Review Board, and informed consent was obtained from all patients. Seventy-one patients with rectal cancer were enrolled in this study. For all patients, both rs-EPI and ss-EPI DWI were performed using a 3T MR scanner. Two radiologists independently assessed the overall image quality, lesion conspicuity, geometric distortion and distinction of anatomical structures. The signal-to-noise ratio (SNR), lesion contrast, contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) were also measured. Comparisons of the quantitative and qualitative parameters between the two sequences were performed using the paired t-test and the Wilcoxon signed rank test. RESULTS: The scores of overall image quality, lesion conspicuity, geometric distortion and distinction of anatomical structures of rs-EPI were all significantly higher than those of ss-EPI (all p<0.05). The SNR and CNR were higher in rs-EPI than those in ss-EPI (all p<0.05). There was no significant difference between ss-EPI and rs-EPI with regard to ROI size and mean ADCs of the tumour (p=0.574 and p=0.479, respectively), but the mean ADC of the normal tissue was higher in rs-EPI than in ss-EPI (1.73+/-0.30*10(-3)mm(2)/s vs. 1.60+/ 0.31*10(-3)mm(2)/s, p=0.001). CONCLUSIONS: DW imaging based on readout-segmented echo-planar imaging is a clinically useful technique to improve the image quality for the purpose of evaluating lesions in patients with rectal tumours. PMID- 27666623 TI - Use of (18)F-FDG PET/CT in the preoperative evaluation of patients diagnosed with peritoneal carcinomatosis of ovarian origin, candidates to cytoreduction and hipec. A pending issue. AB - PURPOSE: To evaluate the clinical usefulness of the results obtained with (18)F FDG PET/CT in relation to CT in the preoperative staging of patients with peritoneal carcinomatosis secondary to primary or recurrent ovarian cancer candidates to cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). MATERIAL AND METHODS: A retrospective study comparing the results obtained with CT and (18)F-FDG PET/CT in the preoperative evaluation of a series of 59 patients was performed. In all patients the peritoneal carcinomatosis index (PCI) was determined by preoperative radiological CT and 18F-FDG PET/CT and compared with surgical PCI, which was considered as reference. RESULTS: Of the 59 patients studied, in 55 peritoneal carcinomatosis presences were confirmed (4 patients had complete responses to neoadjuvant chemotherapy). The mean surgical, CT and 18F-FDG PET/CT PCI was 9.46+/-7.70, 3.69+/-3.96 and 2.25+/-1.02, respectively. In the global disease detection, CT showed a higher positive likelihood ratio (LR+) than (18)F-FDG PET/CT (15.3, 95% CI 8.35-28.04 vs. 3.47, 95% CI 3.36-5.11) and a lower negative likelihood ratio (LR-) than 18F-FDG PET/CT (0.67, 95% CI 0.61-0.73 vs. 0.82, 95% CI 0.76-0.88). In every region of the abdomen the CT showed a greater LR+ than 18F-FDG PET/CT and a lower LR- than 18F-FDG PET/CT. CONCLUSIONS: CT showed the best diagnostic results compared to (18)F-FDG PET/CT to confirme the presence of peritoneal disease. The lower performance of the (18)F-FDG PET/CT suggests that the main utility of (18)F FDG PET/CT is to evaluate a possible metastatic extraperitoneal spread of the disease. PMID- 27666624 TI - Single source dual-energy computed tomography in the diagnosis of gout: Diagnostic reliability in comparison to digital radiography and conventional computed tomography of the feet. AB - OBJECTIVES: To investigate the diagnostic value of single-source dual-energy computed tomography (SDECT) in gouty arthritis and to compare its capability to detect urate depositions with digital radiography (DR) and conventional computed tomography (CT). METHODS: Forty-four patients who underwent SDECT volume scans of the feet for suspected gouty arthritis were retrospectively analyzed. SDECT, CT (both n=44) and DR (n=36) were scored by three blinded readers for presence of osteoarthritis, erosions, and tophi. A diagnosis was made for each imaging modality. Results were compared to the clinical diagnosis using the American College of Rheumatology (ACR) classification criteria. RESULTS: The patient population was divided into a gout (n=21) and control (n=23) group based on final clinical diagnosis. Osteoarthritis was evident in 15 joints using CT and 30 joints using DR (p=0.165). There were 134 erosions detected by CT compared to 38 erosions detected by DR (p<0.001). In total 119 tophi were detected by SDECT, compared to 85 tophi by CT (p=0.182) and 25 tophi by DR (p<0.001). SDECT had best diagnostic value for diagnosis of gout compared to DR and conventional CT (sensitivity and specificity for SDECT: 71.4% and 95.7%, CT: 71.4% and 91.3% and DR: 44.4% and 83.3%, respectively). For all three readers, Cohen's kappa for DR and conventional CT were substantial for all scoring items and ranged from 0.75 to 0.77 and 0.72-0.76, respectively. For SDECT Cohen's kappa was good to almost perfect with 0.77-0.84. CONCLUSIONS: SDECT is capable to detect uric acid depositions with good sensitivity and high specificity in feet, therefore diagnostic confidence is improved. Using SDECT, inter-reader variance can be markedly reduced for the detection of gouty tophi. PMID- 27666625 TI - New radiologic classification of renal angiomyolipomas. AB - PURPOSE: To introduce a new radiologic classification of renal angiomyolipoma (AML). MATERIALS AND METHODS: Between 1995 and 2014, CT or MR images in 98 patients with histologically proven 98 AMLs were reviewed independently by a radiologist and a resident. The lesions were classified as (a) 53 fat-rich AML (<=-10HU), (b) 22 fat-poor AML (>-10HU) with tumor-to-spleen ratio (TSR) <0.71 or signal intensity index (SII) >16.5%, and (c) 23 fat-invisible AML (>-10HU) with TSR >=0.71 and SII <=16.5%. Inter-reader agreement was assessed with a weighted kappa value. Fat-poor and fat-invisible AMLs were compared in terms of attenuation value, TSR, and SII using unpaired t-test. RESULTS: The weighted kappa value was 0.956 (95% confidence interval, 92.0-99.1%). When a region of interest (ROI) was placed within the most hypodense area on unenhanced CT or within the most signal-dropped area on chemical shift image, the mean attenuation values, TSRs, and SIIs of fat-poor versus fat-invisible AMLs were 19.5+/-8.1 HU versus 38.1+/-9.9 HU, 0.59+/-0.19 versus 0.96+/-0.01, and 43.7+/-16.9% versus 5.4+/-21.1%, respectively (p<0.0001). When a ROI was placed within the other area on CT or chemical shift images, 90.1% (48/53) of fat-rich AMLs were mis classified as fat-poor or fat-invisible AML and 50% (11/22) of fat-poor AMLs as fat-invisible AML. CONCLUSION: The new radiologic classification of renal AML is feasible for clinical practice. ROI location is important in differentiating the types of AMLs. PMID- 27666626 TI - Dual-energy computed tomography for characterizing urinary calcified calculi and uric acid calculi: A meta-analysis. AB - OBJECTIVE: A meta-analysis was conducted to determine the accuracy of dual-energy computed tomography (DECT) for differentiating urinary uric acid and calcified calculi. METHODS: The databases PubMed, EMBASE, Web of Science, and the Cochrane Library were searched up to May 2016 for relevant original studies. Data were extracted to calculate the pooled sensitivity, specificity, diagnostic odds ratio (OR), positive and negative likelihood ratios (PLR and NLR), and areas under summary receiver operating characteristic (AUROC) curves for analysis. RESULTS: Nine studies (609 stones in 415 patients) were included. For differentiating uric acid (UA) and non-UA calculi with DECT, the analysis indicated: pooled weighted sensitivity, 0.955 (95% CI, 0.888-0.987); specificity, 0.985 (95% CI, 0.970 0.993); PLR, 0.084 (95% CI, 0.041-0.170); NLR 33.327 (95% CI, 18.516-59.985); and diagnostic OR 538.18 (95% CI, 195.50-1478.5). The AUROC value was 0.9901. For calcified stones, the analysis indicated: pooled weighted sensitivity, 0.994 (95% CI, 0.969-1); specificity, 0.973 (95% CI, 0.906-0.997); PLR, 11.200 (95% CI, 4.922-25.486); NLR 0.027 (95% CI, 0.010-0.072); and diagnostic OR 654.89 (95% CI, 151.31-2834.4). The AUROC value was 0.9915. CONCLUSION: This meta-analysis found that DECT is a highly accurate noninvasive method for characterizing urinary uric acid and calcified calculi. PMID- 27666628 TI - The clinical and radiological importance of extraarticular contrast material leakage into adjacent synovial compartments on ankle MR arthrography in patients with OCD and anterolateral impingement. AB - PURPOSE: To evaluate the tibiotalar joint capacity and the localisation, frequency and amount of extravasation in patients with extraarticular contrast material leakage into adjacent synovial compartments on ankle magnetic resonance (MR) arthrography. MATERIALS AND METHODS: Sites of extravasation were determined in the ankle MR arthrograms of 69 patients. Thirty-four patients without extraarticular contrast material leakage into locations unrelated to the injection path were included as a control group. Volumetric measurements of extraarticular contrast material leakage and the tibiotalar joint capacity were performed on a three dimensional (3D) volume measurement workstation. RESULTS: Extravasation of contrast material occurred through the anterior, posterior, and anterolateral recesses of the tibiotalar joint. The most common site of extravasation was along the flexor hallucis longus tendon synovium (24.6%). The amount of extravasation was significantly higher in patients with ankle osteochondritis dissecans (OCD) than in patients with a different diagnosis (p=0.039). Loose bodies were detected in all OCD's patients with insufficient tibiotalar joint distention. CONCLUSIONS: Connections between the ankle joint and neighboring synovial compartments can decrease the diagnostic value of ankle MR arthrography examinations due to inadequate joint distention. Large injection volumes should be used for ankle MR arthrography of patients with OCD (especially OCD's patients with loose body) and impingement syndrome. PMID- 27666629 TI - Prediction of the therapeutic response after FOLFOX and FOLFIRI treatment for patients with liver metastasis from colorectal cancer using computerized CT texture analysis. AB - PURPOSE: To determine whether baseline CT texture analysis of hepatic metastasis from colorectal cancer (CRC) is predictive of therapeutic response after cytotoxic chemotherapy. MATERIALS AND METHODS: 235 patients with liver metastasis from CRC who underwent CT and cytotoxic chemotherapy using FOLFOX and FOLFIRI were divided into derivation cohort (n=145) and validation cohort (n=90). The CT texture of the hepatic metastasis was quantified using baseline CT. We analyzed the independent predictor for the response from derivation cohort and validated it using validation cohort. We also compared texture features between included four CT scanners. RESULTS: 89 responding and 146 non-responding patients were evaluated. In the derivation cohort, lower skewness (OR, 6.739) in 2D, higher mean attenuation (OR, 2.587), and narrower standard deviation (SD) (OR, 3.163) in 3D were independently associated with response to chemotherapy. However, only lower skewness (P=0.213) on 2D and narrower SD on 3D analysis (P=0.097) did not show a significant difference on either CT scanner. When applied to the validation set, the lower skewness on 2D (AUC=0.797) and narrower SD on 3D (AUC=0.785) showed good performance. CONCLUSION: CT texture analysis is useful for prediction of therapeutic response after cytotoxic chemotherapy in patients with liver metastasis from colorectal cancer. PMID- 27666627 TI - Cloud-processed 4D CMR flow imaging for pulmonary flow quantification. AB - OBJECTIVES: In this study, we evaluated a cloud-based platform for cardiac magnetic resonance (CMR) four-dimensional (4D) flow imaging, with fully integrated correction for eddy currents, Maxwell phase effects, and gradient field non-linearity, to quantify forward flow, regurgitation, and peak systolic velocity over the pulmonary artery. METHODS: We prospectively recruited 52 adult patients during one-year period from July 2014. The 4D flow and planar (2D) phase contrast (PC) were acquired during same scanning session, but 4D flow was scanned after injection of a gadolinium-based contrast agent. Eddy-currents were semi automatically corrected using the web-based software. Flow over pulmonary valve was measured and the 4D flow values were compared against the 2D PC ones. RESULTS: The mean forward flow was 92 (+/-30) ml/cycle measured with 4D flow and 86 (+/-29) ml/cycle measured with 2D PC, with a correlation of 0.82 and a mean difference of -6ml/cycle (-41-29). For the regurgitant fraction the correlation was 0.85 with a mean difference of -0.95% (-17-15). Mean peak systolic velocity measured with 4D flow was 92 (+/-49) cm/s and 108 (+/-56) cm/s with 2D PC, having a correlation of 0.93 and a mean difference of 16cm/s (-24-55). CONCLUSION: 4D flow imaging post-processed with an integrated cloud-based application accurately quantifies pulmonary flow. However, it may underestimate the peak systolic velocity. PMID- 27666630 TI - Soft tissue masses with myxoid stroma: Can conventional magnetic resonance imaging differentiate benign from malignant tumors? AB - OBJECTIVES: To retrospectively evaluate the diagnostic performance of morphological signs observed on conventional magnetic resonance (MR) imaging to differentiate benign from malignant peripheral solid tumors of soft tissue with myxoid stroma. METHODS: MR images from 95 consecutive histopathologically proven tumors (26 benign and 69 malignant) of soft tissues with myxoid components were evaluated in our tertiary referral center. Two radiologists, blind to pathology results, independently reviewed conventional MR sequences including at least a) one T2-weighted sequence with or without fat suppression; b) one T1-weighted sequence without fat suppression; and c) one T1-weighted sequence with gadolinium complex contrast enhancement and fat suppression. Multiple criteria were defined to analyze morphology, margins, architecture and tumor periphery and evaluated for each lesion. Intra- and inter-observer reproducibility and Odds ratios were calculated for each criterion. RESULTS: The most relevant and reproducible criteria to significantly predict malignancy were: (1) ill-defined tumor margins, (2) a hemorrhagic component, (3) intra-tumoral fat, (4) fibrosis and (5) the "tail sign". A lesion is classified as malignant if any of these 5 criteria is present, and benign if none of them are observed. Therefore, this combination provides a sensitivity of 92.9% and a specificity of 93.3%. CONCLUSION: Conventional MR imaging provides reproducible criteria that can be combined to differentiate between benign and malignant solid tumors of soft tissue with myxoid stroma. PMID- 27666631 TI - Dynamic (4D) CT perfusion offers simultaneous functional and anatomical insights into pulmonary embolism resolution. AB - OBJECTIVE: Resolution and long-term functional effects of pulmonary emboli are unpredictable. This study was carried out to assess persisting vascular bed perfusion abnormalities and resolution of arterial thrombus in patients with recent pulmonary embolism (PE). METHODS AND MATERIALS: 26 Patients were prospectively evaluated by dynamic (4D) contrast enhanced CT perfusion dynamic pulmonary CT perfusion. Intermittent volume imaging was performed every 1.5-1.7s during breath-hold and perfusion values were calculated by maximum-slope technique. Thrombus load (modified Miller score; MMS) and ventricular diameter were determined. Perfusion maps were visually scored and correlated with residual endoluminal filling defects. RESULTS: The mean initial thrombus load was 13.1+/ 4.6 MMS (3-16), and 1.2+/-2.1 MMS (0-8) at follow up. From the 24 CTPs with diagnostic quality perfusion studies, normal perfusion was observed in 7 (29%), and mildly-severely abnormal in 17 (71%). In 15 patients with no residual thrombus on follow up CTPA, normal perfusion was observed in 6, and abnormal perfusion in 9. Perfusion was abnormal in all patients with residual thrombus on follow up CTPA. Pulmonary perfusion changes were classified as reduced (n=4), delayed (systemic circulation pattern; n=5), and absent (no-flow; n=5). The right ventricle was dilated in 12/25 (48%) at presentation, and normal in all 26 follow up scans. Weak correlation was found between initial ventricular dilatation and perfusion abnormality at follow up (r=0.15). CONCLUSIONS: Most patients had substantial perfusion abnormality at 3-6 months post PE. Abnormal perfusion patterns were frequently observed in patients and in regions with no corresponding evidence of residual thrombus on CTPA. Some defects exhibit delayed, presumed systemic, enhancement (which we have termed 'stunned' lung). CT perfusion provides combined anatomical and functional information about PE resolution. PMID- 27666632 TI - Liver resection for intrahepatic cholangiocarcinoma in AJCC-stage IV: An evaluation of the survival benefit and prognostic accuracy of current AJCC staging system on N and M classification. AB - Intrahepatic cholangiocarcinoma (ICC) is usually confirmed in advanced stage at the time of diagnosis or after surgical exploration, however, indication of surgical treatment is usually controversial for ICC in advanced stages. This retrospective study aims to evaluate clinical value of surgery for such tumors, in order to identify the appropriate patients who will benefit from surgery, and to evaluate the prognostic accuracy of the current staging system for advanced ICC. From January 2007 to December 2011, 387 consecutive surgically treated patients with ICC in AJCC-stage IV were evaluated. Survival was compared among different patients grouped by different elements of AJCC staging system. The prognostic importance of extent of lymph node (LN) metastasis relative to the AJCC N and M classification system was assessed. Our data showed that survival was much better for patients in AJCC-stage IVA group (median survival time, MST, 9.0 months) than in AJCC-stage IVB group (MST, 5.0 months) (P<0.001). While in AJCC-stage IVB group, survival for patients in AnyTN2-3M0 subgroup (MST, 9.0 months) was much better than in AnyTN0M1 subgroup (MST, 3.0 months); and better than in AnyTN2-3M1 subgroup (MST, 4.0 months) (P<0.001). Overall, R0 and R1 liver resection should be indicated for patients in AJCC-stage IVA group and AnyTN2-3M0 subgroup in AJCC-stage IVB group, as patients in these groups will benefit from surgery with relatively better survival. Staging of advanced ICC by N2-3 instead of M1 for extended LN metastasis classification is superior in comparison with the AJCC staging system. PMID- 27666633 TI - Systemic structure-activity relationship study of phenyl polyyne diols as potential chemopreventive agents. AB - The present study reports the cancer chemopreventive activities of phenyl polyyne diols derived from polyacetylene triol. Thirty-seven analogues based on a 1 phenylhexa-2,4-diyne-1,6-diol scaffold were prepared and their effects on QR activity were elucidated, as well as their cytotoxicities. We found that most of the derivatives based on phenylhexa-2,4-diyne-1,6-diol exhibited good QR induction activity and relatively low cytotoxicity and systemic structure activity relationship was revealed. In particular, 4-fluorophenyl, 3 chlorophenyl, and 3,4-dioxolophenyl derivatives showed the best profiles in terms of QR induction, cytotoxicity, and CI. PMID- 27666634 TI - Pterin-7-carboxamides as a new class of aldose reductase inhibitors. AB - Aldose reductase is related to the onset and progression of diabetic complications, such as neuropathy, retinopathy, angiopathy, and so on: therefore molecules that are capable of inhibiting the enzyme are potential drugs for treatment of diabetic complications. Epalrestat is the sole aldose reductase inhibitor that is clinically used, but still has some drawbacks. Thus, the development of new aldose reductase inhibitors is still desired. We have synthesized a series of new pterin-7-carboxamides, and evaluated their in vitro inhibitory activities against human aldose reductase. All newly synthesized compounds exhibited the inhibitory activity. Among them, 1a having a glycine side chain exhibits the highest activity comparable to that of sorbinil, a highly active aldose reductase inhibitor. Molecular docking of 1a on the active site of the enzyme indicated this compound interacts with amino acid residues that are specific to the enzyme and related to suppressing side effects. Based on these results, we proved perin-7-carboxamides to be a new class of aldose reductase inhibitors, and particularly compound 1a was found to be a good candidate for further biological investigations as a drug for treatment of diabetic complications with fewer side effects. PMID- 27666635 TI - Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand. AB - The manipulation of protein stability with small molecules has great potential as a technique for aiding the development of clinical therapies, including treatments for cancer. In this study, BCR-ABL protein degradation inducers called SNIPER(ABL) (Specific and Non-genetic inhibitors of apoptosis protein [IAP] dependent Protein Erasers) were developed. The designed molecules contained two biologically active scaffolds: one was an imatinib derivative that binds to BCL ABL and the other was a methyl bestatin that binds to cellular IAP 1 (cIAP1). The hybrid molecules, SNIPER(ABL), were expected to recruit BCR-ABL to cIAP1 for removal by proteasomes. In fact, SNIPER(ABL) induced the degradation of BCR-ABL protein and a subsequent reduction in cell growth. Thus, the degradation of BCR ABL by SNIPER(ABL) is one potential strategy for treating BCR-ABL driven chronic myelogenous leukemia. PMID- 27666636 TI - Spike-timing-dependent plasticity enhanced synchronization transitions induced by autapses in adaptive Newman-Watts neuronal networks. AB - In this paper, we numerically study the effect of spike-timing-dependent plasticity (STDP) on synchronization transitions induced by autaptic activity in adaptive Newman-Watts Hodgkin-Huxley neuron networks. It is found that synchronization transitions induced by autaptic delay vary with the adjusting rate Ap of STDP and become strongest at a certain Ap value, and the Ap value increases when network randomness or network size increases. It is also found that the synchronization transitions induced by autaptic delay become strongest at a certain network randomness and network size, and the values increase and related synchronization transitions are enhanced when Ap increases. These results show that there is optimal STDP that can enhance the synchronization transitions induced by autaptic delay in the adaptive neuronal networks. These findings provide a new insight into the roles of STDP and autapses for the information transmission in neural systems. PMID- 27666637 TI - Utilization of smart phones related medical applications among medical students at King Abdulaziz University, Jeddah: A cross-sectional study. AB - INTRODUCTION: The present study explored the utility, attitude, and trends regarding Smartphone related Medical Applications (Apps) among medical students of King Abdulaziz University (KAU) Jeddah, Saudi Arabia (SA) and their perceptions of the impact of Medical Apps in their training activities. SUBJECTS AND METHODS: This survey was conducted at the Faculty of Medicine, Jeddah, and Rabigh campuses, KAU, Jeddah, SA. All participants were medical students of 2nd to 6th year. The data was collected by using an anonymous questionnaire regarding the perception of medical students about Medical Apps on the smart devices and the purpose of installation of the Apps. Additionally examined was the use of different Medical Apps by the students to investigate the impact of Medical Apps on the clinical training/practice. Data was analyzed on SPSS 21. RESULTS: The opinion of 330/460 medical students from all academic years was included in the study with a response rate of 72%. There were 170 (51.5%) males and 160 (48.5%) females with a mean age of 21.26+/-1.86 years. Almost all participating students 320 (97%) were well aware of Medical Apps for smart devices and 89.1% had installed different applications on their smart devices. The main usage was for either revision of courses (62.4%) or for looking up of medical information (67.3%), followed by preparing for a presentation (34.5%) and getting the medical news (32.1%). Regarding the impact of Medical Apps, most of the students considered these helpful in clinical decision-making, assisting in differential diagnosis, allowing faster access to Evidence-Based Medical practice, saving time and others. The practical use of these Apps was found to be minimal in medical students. Around 73% were occasional users of Medical Apps, and only 27% were using Medical Apps at least once a day. CONCLUSION: The regular use of Medical Apps on mobile devices is not common among medical students of KAU. PMID- 27666638 TI - Development of a rapid response plan for intraoperative emergencies: the Circulate, Scrub, and Technical Assistance Team. AB - BACKGROUND: Unplanned intraoperative events are inevitable and cause stress and inefficiency among staff. We believe that developing a technical rapid response team with explicitly defined, narrow roles would reduce the amount of chaos during such emergencies. This article provides a detailed description of the development and implementation of such a program. METHODS: In-situ simulation of an intraoperative emergency was used for a formal assessment of the current practice. Debriefing sessions identified areas of improvement and solicited solutions. A multidisciplinary working group then developed and implemented the technical rapid response team based on the needs assessment. The program was designed to create a Circulating, Scrubbing, and Technical Assistance Team that helps with equipment, supplies, anesthesia, and communication. RESULTS: We anticipate the program will foster a culture of safety, and promote positive relationships and attitudes of the entire multidisciplinary team. CONCLUSIONS: In the future, research regarding patient outcomes and staff satisfaction and safety attitudes may help provide objective evidence of the benefits of the program. PMID- 27666639 TI - Patient-centered communication during procedures. PMID- 27666640 TI - Implementation results of a novel comprehensive mental skills curriculum during simulator training. AB - BACKGROUND: Mental skills training refers to the implementation of cognitive performance-enhancing strategies to promote optimal performance. We aimed to develop a surgery-specific mental skills curriculum (MSC) and obtain initial evidence of efficacy. METHODS: The developed MSC consisted of 8 proven performance-enhancing modules. Its efficacy was assessed during laparoscopic simulator-based practice by novices using validated instruments of mental skills, workload, and stress, in addition to a skill transfer test to a porcine model. A paired t test was used to analyze the data. RESULTS: Nine surgical novices completed the curriculum. Compared with baseline assessment, participants improved significantly their laparoscopic performance and mental skills after completion of the MSC. All participants completed the task in the porcine model without an appreciable change in their perceived stress. During the skill transfer test, 8 participants were observed using mental skills taught in the MSC. CONCLUSIONS: A surgery-specific simulator-based MSC was developed, and its efficacy in improving mental skills and surgical performance was supported during a surgical skill transfer test. PMID- 27666641 TI - Reply to "Open reduction and internal fixation of rib fractures in polytrauma patients with flail chest" by DeFreest et al. PMID- 27666642 TI - About the importance of the acute phase of subarachnoid hemorrhage and the chances for successful translation. PMID- 27666644 TI - Does symbolism benefit environmental and business performance in the adoption of ISO 14001? AB - Much research has focused on the organisational and reputational benefits of ISO 14001. However, less discussed is the symbolic adoption that some firms are implementing without experiencing significant reductions in environmental impacts. This work analyses the relationships between the different ISO 14001 adoption profiles (from symbolic profile to factual approach) and both environmental performance and profitability. These relationships are examined using a sample of 1214 manufacturing firms in 7 OECD countries while controlling for selection bias. The results suggest that only ISO 14001 adopters that monitor an extensive set of negative environmental impacts are associated with real improvements in both environmental performance and business performance. PMID- 27666643 TI - Hydroxyapatite precipitation with Hydron Blue dye. AB - Calcium phosphate, in the form of amorphous hydroxyapatite, precipitates out of neutral water solutions containing calcium and phosphate ions in the form of small agglomerates of 18 MUm average size. When Hydron Blue dye (HB) is added, the insoluble particles gradually agglomerate further to 50 MUm sizes. However, the removal capacity of hydroxyapatite for the dye is increased when the calcium phosphate nucleates and forms in the presence of dye. When coprecipitates form, the particules average 20 MUm size and contain up to 60% organic matter. Nascent calcium phosphate particles have strong capacity for Hydron Blue dye removal. Thus smaller calcium phosphate particles increase the amount of dye molecules in water pollution control. PMID- 27666645 TI - End-product quality of composts produced under tropical and temperate climates using different raw materials: A meta-analysis. AB - A meta-analysis on end-product quality of 442 composts was performed to assess the effects of climate and raw materials on compost quality. The analysis was performed using an ANOVA including a mixed model with nested factors (climate, raw material and publication effect). Tropical composts presented lower carbon, nitrogen, potassium and soluble-carbon contents, and higher electrical conductivity. The results suggest that compost quality in the tropics was affected by weather conditions during composting (e.g. high temperature and rainfall), which induced high losses of carbon and nutrients. For most properties, industrial, sewage sludge and manure-based composts displayed the highest quality under both climates, while the contrary was found for household and municipal solid waste-based composts. The publication effect represented >50% of total variance, which was mainly due to the heterogeneity of the composting procedures. The meta-analysis was found to be a helpful tool to analyse the imbalanced worldwide database on compost quality. PMID- 27666646 TI - Removal of organic matter and ammonium from landfill leachate through different scenarios: Operational cost evaluation in a full-scale case study of a Flemish landfill. AB - Several scenarios are available to landfilling facilities to effectively treat leachate at the lowest possible cost. In this study, the performance of various leachate treatment sequences to remove COD and nitrogen from a leachate stream and the associated cost are presented. The results show that, to achieve 100% nitrogen removal, autotrophic nitrogen removal (ANR) or a combination of ANR and nitrification - denitrification (N-dN) is more cost effective than using only the N-dN process (0.58 ?/m3) without changing the leachate polishing costs associated with granular activated carbon (GAC). Treatment of N-dN effluent by ozonation or coagulation led to the reduction of the COD concentration by 10% and 59% respectively before GAC adsorption. This reduced GAC costs and subsequently reduced the overall treatment costs by 7% (ozonation) and 22% (coagulation). On the contrary, using Fenton oxidation to reduce the COD concentration of N-dN effluent by 63% increased the overall leachate treatment costs by 3%. Leachate treatment sequences employing ANR for nitrogen removal followed by ozonation or Fenton or coagulation for COD removal and final polishing with GAC are on average 33% cheaper than a sequence with N-dN + GAC only. When ANR is the preceding step and GAC the final step, choice of AOP i.e., ozonation or Fenton did not affect the total treatment costs which amounted to 1.43 (ozonation) and 1.42 ?/m3 (Fenton). In all the investigated leachate treatment trains, the sequence with ANR + coagulation + GAC is the most cost effective at 0.94 ?/m3. PMID- 27666647 TI - Ecosystem water imbalances created during ecological restoration by afforestation in China, and lessons for other developing countries. AB - Land degradation is a global environmental problem that jeopardizes human safety and socioeconomic development. To alleviate severe soil erosion and desertification due to deforestation and overgrazing, China has implemented historically unprecedented large-scale afforestation. However, few studies have accounted for the resulting imbalance between water supply (primarily precipitation) and water consumption (evapotranspiration), which will affect ecosystem health and socioeconomic development. We compared the water balance results between restoration by means of afforestation and restoration using the potential natural vegetation to guide future ecological restoration planning and environmental policy development. Based on estimates of water consumption from seven evapotranspiration models, we discuss the consequences for water security using data obtained since 1952 under China's large-scale afforestation program. The models estimated that afforestation will increase water consumption by 559 2354 m3/ha annually compared with natural vegetation. Although afforestation is a potentially important approach for environmental restoration, China's current policy has not been tailored to local precipitation conditions, and will have therefore exacerbated water shortages and decrease the ability to achieve environmental policy goals. Our analysis shows how, both in China and around the world, future ecological restoration planning must account for the water balance to ensure effective and sustainable environmental restoration policy. PMID- 27666649 TI - A scenario-based MCDA framework for wastewater infrastructure planning under uncertainty. AB - Wastewater infrastructure management is increasingly important because of urbanization, environmental pollutants, aging infrastructures, and climate change. We propose a scenario-based multi-criteria decision analysis (MCDA) framework to compare different infrastructure alternatives in terms of their sustainability. These range from the current centralized system to semi- and fully decentralized options. Various sources of uncertainty are considered, including external socio-economic uncertainty captured by future scenarios, uncertainty in predicting outcomes of alternatives, and incomplete preferences of stakeholders. Stochastic Multi-criteria Acceptability Analysis (SMAA) with Monte Carlo simulation is performed, and rank acceptability indices help identify robust alternatives. We propose step-wise local sensitivity analysis, which is useful for practitioners to effectively elicit preferences and identify major sources of uncertainty. The approach is demonstrated in a Swiss case study where ten stakeholders are involved throughout. Their preferences are quantitatively elicited by combining an online questionnaire with face-to-face interviews. The trade-off questions reveal a high concern about environmental and an unexpectedly low importance of economic criteria. This results in a surprisingly good ranking of high-tech decentralized wastewater alternatives using urine source separation for most stakeholders in all scenarios. Combining scenario planning and MCDA proves useful, as the performance of wastewater infrastructure systems is indeed sensitive to socio-economic boundary conditions and the other sources of uncertainty. The proposed sensitivity analysis suggests that a simplified elicitation procedure is sufficient in many cases. Elicitation of more information such as detailed marginal value functions should only follow if the sensitivity analysis finds this necessary. Moreover, the uncertainty of rankings can be considerably reduced by better predictions of the outcomes of alternatives. Although the results are case based, the proposed decision framework is generalizable to other decision contexts. PMID- 27666648 TI - Unpacking the concept of land degradation neutrality and addressing its operation through the Rio Conventions. AB - The world's commitment towards land degradation neutrality (LDN) became enshrined in various international agreements and decisions throughout the year 2015. The challenge now becomes one of addressing its operation, in order to achieve these new policy goals and targets by the year 2030. Advancing LDN demands attention to what the concept seeks to achieve, as well as unravelling the perspectives of the key multi-lateral environmental agreements through which progress can be made. The three Rio Conventions (the UN Convention to Combat Desertification (UNCCD), the UN Framework Convention on Climate Change (UNFCCC) and the Convention on Biological Diversity (CBD)) all play key roles in shaping the international LDN governance and implementation context. Their different but related foci create a number of challenges and opportunities for advancing LDN. In this paper we critically analyze the literature to elucidate potential challenges and opportunities in moving LDN towards implementation, considering the mandates and objectives of all three Rio Conventions. We first unpack the concept of LDN's aspirations. We highlight the importance of the definitions and terminology used, and the relationships between those definitions, terms and the actors using them, as well as their implications in framing the range of policy actions and synergies that could benefit progress towards multiple Sustainable Development Goals. We then examine the LDN pilot project spearheaded by the UNCCD to identify key lessons for LDN implementation. Synthesizing these lessons, we present a portfolio of blended interventions that seeks to address the aspirations of the UNCCD, UNFCCC and CBD in the LDN space, identifying synergistic options for national actions to move towards LDN. Overall, our analysis provides insights in advancing LDN from its current position as a policy target, towards synergetic action. PMID- 27666650 TI - Asthma transition from childhood into adulthood. AB - Asthma is the most prevalent chronic respiratory disease both in children and adults and resembles a complex syndrome rather than a single disease. Different methods have been developed to better characterise distinct asthma phenotypes in childhood and adulthood. In studies of adults, most phenotyping relies on biomaterials from the lower airways; however, this information is missing in paediatric studies because of restricted accessibility. Few patients show symptoms throughout childhood, adolescence, and adulthood. Risk factors for this might be genetics, family history of asthma and atopy, infections early in life, allergic diseases, and lung function deficits. In turn, a large proportion of children with asthma lose their symptoms during school age and adolescence. This improved prognosis, which might also reflect a better treatment response, is associated with being male and with milder and less allergic disease. Importantly, whether clinical remission of symptoms equals the disappearance of underlying pathology is unknown. In fact, airway hyper-responsiveness and airway inflammation might remain despite the absence of overt symptoms. Additionally, a new-onset of asthma symptoms is apparent in adulthood, especially in women and in the case of impaired lung function. However, many patients do not remember childhood symptoms, which might reflect relapse rather than true initiation. Both relapse and adult-onset of asthma symptoms have been associated with allergic disease and sensitisation in addition to airway hyper-responsiveness. Thus, asthma symptoms beginning in adults might have originated in childhood. Equivocally, persistence into, relapse, and new-onset of symptoms in adulthood have all been related to active smoking. However, underlying mechanisms for the associations remain unclear, and future asthma research should therefore integrate standardised molecular approaches in identical ways in both paediatric and adult populations and in longitudinal studies. PMID- 27666651 TI - An Evaluation of the Breathing Strategies and Maximum Phonation Time in Musical Theater Performers During Controlled Performance Tasks. AB - OBJECTIVES: Breathing strategies for athletic dancing are quite different from those needed for legato singing. This study considers the respiration data recorded by a telemetric heart rate monitor, mask, and gas analyzer collected from 20 musical theater professionals performing set tasks. METHODS: Scores were taken of maximum phonation time (MPT), relative oxygen uptake, and heart rate immediately after three tasks: (1) singing only, (2) dancing only, and (3) singing while dancing. Scores were also collected of the ability to sustain unbroken notes immediately before performing and then immediately after each of the above tasks (1), (2), and (3). Vital capacity scores were recorded at the beginning and at the end of the testing schedule. A questionnaire took demographic information and asked questions regarding performer perception, training, and experience. Most were aware of breathing inconsistencies and adjustments related to changes of task and/or direction. RESULTS: (Means) Tidal volume was constant for (1) singing and (2) dancing; MPT reduced by 65.2% for singing while dancing; and minute volumes reduced by 16% but relative oxygen uptake (mL/kg/min) remained unchanged, despite increased heart rates, and when singing while dancing compared with dancing only. The mean MPT dropped from 20.4 seconds to 7.1 seconds (change of 65.2%) between the at rest and postsinging while dancing scores. CONCLUSION: The likelihood of developing vocal dysfunction (overtime) and the risk of compromising performance aesthetic lead the researchers to the conclusion that further study is required in this area. PMID- 27666652 TI - VHI-10 and SVHI-10 Differences in Singers' Self-perception of Dysphonia Severity. AB - OBJECTIVE: Previous investigations of the Voice Handicap Index (VHI)-10 in clinical practice noted that specific information relevant to singers was not forthcoming. Consequently, a second index, the Singing Voice Handicap Index (SVHI) as well as its shortened counterpart the SVHI-10, was developed. The purpose of this study was to directly compare the differences in scores between the VHI-10 and the SVHI-10 in a group of 50 singers. METHODS: A retrospective chart review of 50 singers (26 women, 24 men) was performed between June 2014 and November 2014 at Weill Cornell Medical College, New York. Subjects completed both the VHI-10 and the SVHI-10 at their initial evaluation. The results from the VHI 10 and the SVHI-10 were then compared using paired t test and two-way analysis of variance. RESULTS: The SVHI-10 scores from the performers were significantly higher than those of the VHI-10 (P < 0.0001). The mean score on the VHI-10 was 12.1 compared with 20.4 on the SVHI-10 (maximum score for each questionnaire is 40). There were no significant gender differences when comparing the VHI-10 and the SVHI-10 on the overall scores or for individual items. The analysis of variance also found no significant gender difference (P = 0.865) and confirmed a significant difference between VHI-10 and SVHI-10 (P = 0.0003). CONCLUSION: Whereas singers may have general complaints about their voice, they also have specific complaints that relate only to their singing voice. Finding a significant difference between the scores of the VHI-10 and the SVHI-10 suggests the importance of assessing the singer's perception of voice severity using a tool that focuses on the singing voice. PMID- 27666653 TI - Technical note: Preservation of Trichomonas vaginalis viability in urine for laboratorial diagnosis by the wet mount examination. AB - This study compared preservative solutions at different temperatures aiming to improve the wet mount for trichomoniasis diagnosis. The glucose-saline pH6.0 solution preserved the trophozoites up to 6h. The urine samples preservation is crucial for diagnosis and we suggest this solution as part of the clinical laboratorial routine. PMID- 27666654 TI - Folic acid enhances the apoptotic and genotoxic activity of carboplatin in HeLa cell line. AB - In human tumor cells, experimental and clinical evidence indicates that some factors involved in signal transduction and cell growth can also modulate the response to chemotherapeutic treatment. The aim of the present study was to investigate the role of folic acid (FA) as a modulator of carboplatin (CBDCA) activity. Genotoxicity and cytotoxicity induced by CBDCA alone and in combination with FA were assessed in cultured HeLa cells. We used comet assay, mitotic index analysis, MTT and NR assays, cytokinesis-block micronucleus cytome assay and annexin V-IP as different cytotoxicity and genotoxicity approaches for human cervical carcinoma cell line studies. The results showed that addition of 900nM FA together with 40.4mM CBDCA enhanced the activity of the platinum compound, increasing its effect on cell death by nearly 20%, as evidenced by the MTT and NR assays. Moreover, not only higher levels of DNA and chromosomal damage were reached but also the number of necrotic and apoptotic cells were significantly increased when cell cultures were treated with the combined procedure. This situation opens the possibility to explore the use of FA in platinum-based chemotherapy protocols to reduce the platinum doses for patient treatment and decrease the chance of developing the known side effects without losing biological activity. PMID- 27666656 TI - Development and Evaluation of the American College of Surgeons NSQIP Pediatric Surgical Risk Calculator. AB - BACKGROUND: There is an increased desire among patients and families to be involved in the surgical decision-making process. A surgeon's ability to provide patients and families with patient-specific estimates of postoperative complications is critical for shared decision making and informed consent. Surgeons can also use patient-specific risk estimates to decide whether or not to operate and what options to offer patients. Our objective was to develop and evaluate a publicly available risk estimation tool that would cover many common pediatric surgical procedures across all specialties. STUDY DESIGN: American College of Surgeons NSQIP Pediatric standardized data from 67 hospitals were used to develop a risk estimation tool. Surgeons enter 18 preoperative variables (demographics, comorbidities, procedure) that are used in a logistic regression model to predict 9 postoperative outcomes. A surgeon adjustment score is also incorporated to adjust for any additional risk not accounted for in the 18 risk factors. RESULTS: A pediatric surgical risk calculator was developed based on 181,353 cases covering 382 CPT codes across all specialties. It had excellent discrimination for mortality (c-statistic = 0.98), morbidity (c-statistic = 0.81), and 7 additional complications (c-statistic > 0.77). The Hosmer-Lemeshow statistic and graphic representations also showed excellent calibration. CONCLUSIONS: The ACS NSQIP Pediatric Surgical Risk Calculator was developed using standardized and audited multi-institutional data from the ACS NSQIP Pediatric, and it provides empirically derived, patient-specific postoperative risks. It can be used as a tool in the shared decision-making process by providing clinicians, families, and patients with useful information for many of the most common operations performed on pediatric patients in the US. PMID- 27666655 TI - Effects of different surface modifying agents on the cytotoxic and antimicrobial properties of ZnO nanoparticles. AB - Zinc oxide (ZnO) nanoparticles (NPs) have received considerable attention in the medical field because of their antibacterial properties, primarily for killing and reducing the activity of numerous microorganisms. The purpose of this study was to determine whether surface-modified ZnO NPs exhibit different properties compared with unmodified ZnO. The antimicrobial and cytotoxic properties of modified ZnO NPs as well as their effects on inflammatory cytokine production were evaluated. ZnO NPs were prepared using a wet chemical method. Then, the surfaces of these NPs were modified using 3-aminopropyltriethoxysilane (APTES) and dimethyl sulfoxide (DMSO) as modifying agents via a chemical hydrolysis method. According to infrared spectroscopy analysis (FTIR), the structure of the ZnO remained unchanged after modification. Antibacterial assays demonstrated that APTES modification is more effective at inducing an antimicrobial effect against Gram-negative bacteria than against Gram-positive bacteria. Cytotoxicity studies showed that cell viability was dose-dependent; moreover, pristine and APTES modified ZnO exhibited low cytotoxicity, whereas DMSO-modified ZnO exhibited toxicity even at a low NP concentration. An investigation of inflammatory cytokine production demonstrated that the extent of stimulation was related to the ZnO NP concentration but not to the surface modification, except for IFN gamma and IL-10, which were not detected even at high NP concentrations. PMID- 27666657 TI - Analysis of heterogeneous dengue transmission in Guangdong in 2014 with multivariate time series model. AB - Guangdong experienced the largest dengue epidemic in recent history. In 2014, the number of dengue cases was the highest in the previous 10 years and comprised more than 90% of all cases. In order to analyze heterogeneous transmission of dengue, a multivariate time series model decomposing dengue risk additively into endemic, autoregressive and spatiotemporal components was used to model dengue transmission. Moreover, random effects were introduced in the model to deal with heterogeneous dengue transmission and incidence levels and power law approach was embedded into the model to account for spatial interaction. There was little spatial variation in the autoregressive component. In contrast, for the endemic component, there was a pronounced heterogeneity between the Pearl River Delta area and the remaining districts. For the spatiotemporal component, there was considerable heterogeneity across districts with highest values in some western and eastern department. The results showed that the patterns driving dengue transmission were found by using clustering analysis. And endemic component contribution seems to be important in the Pearl River Delta area, where the incidence is high (95 per 100,000), while areas with relatively low incidence (4 per 100,000) are highly dependent on spatiotemporal spread and local autoregression. PMID- 27666658 TI - Radiologic Response to Neoadjuvant Treatment Predicts Histologic Response in Thymic Epithelial Tumors. AB - INTRODUCTION: Neoadjuvant treatment might increase resectability of thymic epithelial tumors (TETs). No standardized pathologic grading scheme for tumor response is available. Also, it is unclear whether radiologic treatment response can predict pathologic response. METHODS: Patients with unresectable TETs who underwent neoadjuvant treatment before surgery at Mayo Clinic Rochester (1942 2014) were included. The pathologic tumor response grade (TRG) was based on Mandard grading (1994), ranging from TRG 1 (no viable tumor) to TRG 5 (no regression). TRG was compared with response by computed tomography, including with the Response Evaluation Criteria in Solid Tumors, version 1.1 (Byrne modification). RESULTS: A total of 49 patients, including 29 men, with a median age of 47.6 years and thymomas (n = 28) or thymic carcinomas (n = 21) were included. In five cases, pretreatment tumor type differed from posttreatment diagnosis. Thymic carcinomas had a greater morphologic response to neoadjuvant treatment than did thymomas with a lower percent viable tumor (p < 0.0001) and lower TRG (p<0.0001). Agreement for TRG by three reviewers was good (Krippendorff alpha = 0.838). By imaging (n = 24), partial response and larger reduction in tumor longest diameter and volume were associated with lower TRG (p = 0.0093, p = 0.0042, and p = 0.0021, respectively) and lower percent viable tumor (p = 0.0041, p = 0.0034, and p =0.0019). TRG correlated with radiologic change in tumor longest diameter and volume (Spearman correlation coefficient = 0.59 and 0.61, respectively). Radiologic change in tumor longest diameter and volume reasonably predicted pathologic TRG of 3 to 5 versus 1 or 2 (area under the curve 0.73 and 0.71, respectively). Sixty-seven percent of patients' tumors were completely resected. CONCLUSIONS: Our proposed histologic TRG for TETs appears easy and reproducible and correlates with radiologic response. Radiologic response is useful to predict pathologic response. PMID- 27666660 TI - Representing Something Out of Nothing: The Dawning of Zero. AB - Zero stands for emptiness, for nothing, and yet it is considered to be one of the greatest achievements of humankind. This review first recapitulates the discovery of the number zero in human history, then follows its progression in human development, traces its evolution in the animal kingdom, and finally elucidates how the brain transforms 'nothing' into an abstract zero category. It is argued that the emergence of zero passes through four corresponding representations in all of these interrelated realms: first, sensory 'nothing'; then categorical 'something'; then quantitative empty sets; and finally the number zero. The concept of zero shows how the brain, originally evolved to represent stimuli ('something'), detaches from empirical properties to achieve ultimate abstract thinking. PMID- 27666659 TI - Emergence of Preexisting MET Y1230C Mutation as a Resistance Mechanism to Crizotinib in NSCLC with MET Exon 14 Skipping. AB - INTRODUCTION: MET proto-oncogene, receptor tyrosine kinase gene exon 14 skipping (METex14) alterations represent a unique subset of oncogenic drivers in NSCLC. Preliminary clinical activity of crizotinib against METex14-positive NSCLC has been reported. The full spectrum of resistance mechanisms to crizotinib in METex14-positive NSCLC remains to be identified. METHODS: Hybrid capture-based comprehensive genomic profiling performed on a tumor specimen obtained at diagnosis, and a hybrid capture-based assay of circulating tumor DNA (ctDNA) at the time of progression during crizotinib treatment was assessed in a pairwise fashion. RESULTS: A METex14 alteration (D1010H) was detected in the pretreatment tumor biopsy specimen, as was MET proto-oncogene, receptor tyrosine kinase (MET) Y1230C, retrospectively, at very low frequency (0.3%). After a confirmed response during crizotinib treatment for 13 months followed by progression, both MET proto oncogene, receptor tyrosine kinase gene Y1230C and D1010H were detected prospectively in the ctDNA. CONCLUSION: Emergence of the preexisting MET Y1230C likely confers resistance to crizotinib in this case of METex14-positive NSCLC. Existence of pretreatment MET Y1230C may eventually modulate the response of METex14-positive NSCLC to type I MET tyrosine kinase inhibitors. Noninvasive plasma-based ctDNA assays can provide a convenient method to detect resistance mutations in patients with previously known driver mutations. PMID- 27666662 TI - See-saw relationship of the Holocene East Asian-Australian summer monsoon. AB - The East Asian-Indonesian-Australian summer monsoon (EAIASM) links the Earth's hemispheres and provides a heat source that drives global circulation. At seasonal and inter-seasonal timescales, the summer monsoon of one hemisphere is linked via outflows from the winter monsoon of the opposing hemisphere. Long-term phase relationships between the East Asian summer monsoon (EASM) and the Indonesian-Australian summer monsoon (IASM) are poorly understood, raising questions of long-term adjustments to future greenhouse-triggered climate change and whether these changes could 'lock in' possible IASM and EASM phase relationships in a region dependent on monsoonal rainfall. Here we show that a newly developed nonlinear time series analysis technique allows confident identification of strong versus weak monsoon phases at millennial to sub centennial timescales. We find a see-saw relationship over the last 9,000 years with strong and weak monsoons opposingly phased and triggered by solar variations. Our results provide insights into centennial- to millennial-scale relationships within the wider EAIASM regime. PMID- 27666661 TI - Molecular screening strategies for NF1-like syndromes with cafe-au-lait macules (Review). AB - Multiple cafe-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT proto-oncogene receptor tyrosine kinase and Ras/mitogen-activated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Furthermore, certain syndromes are clinically overlapping and molecular testing is a vital diagnostic method. The present review aims to provide an overview of these 'NF1-like' inherited diseases and recommend a cost effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline. PMID- 27666663 TI - Grassy Silica Nanoribbons and Strong Blue Luminescence. AB - Silicon dioxide (SiO2) is one of the key materials in many modern technological applications such as in metal oxide semiconductor transistors, photovoltaic solar cells, pollution removal, and biomedicine. We report the accidental discovery of free-standing grassy silica nanoribbons directly grown on SiO2/Si platform which is commonly used for field-effect transistors fabrication without other precursor. We investigate the formation mechanism of this novel silica nanostructure that has not been previously documented. The silica nanoribbons are flexible and can be manipulated by electron-beam. The silica nanoribbons exhibit strong blue emission at about 467 nm, together with UV and red emissions as investigated by cathodoluminescence technique. The origins of the luminescence are attributed to various defects in the silica nanoribbons; and the intensity change of the blue emission and green emission at about 550 nm is discussed in the frame of the defect density. Our study may lead to rational design of the new silica-based materials for a wide range of applications. PMID- 27666664 TI - A3 adenosine receptor agonist, CF102, protects against hepatic ischemia/reperfusion injury following partial hepatectomy. AB - Ischemia/reperfusion (IR) injury during clinical hepatic procedures is characterized by inflammatory conditions and the apoptosis of hepatocytes. Nuclear factor-kappaB (NF-kappaB), nitric oxide and the expression levels of inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 were observed to increase following IR and mediate the inflammatory response in the liver. CF102 is a highly selective A3 adenosine receptor (A3AR) agonist, and has been identified to induce an anti-inflammatory and protective effect on the liver via the downregulation of the NF-kappaB signaling pathway. The present study aimed to determine the effect of CF102 on protecting the liver against IR injury. The potential protective effect of CF102 (100 ug/kg) was assessed using an IR injury model on 70% of the liver of Wistar rats, which was induced by clamping the hepatic vasculature for 30 min. The regenerative effect of CF102 was assessed by the partial hepatectomy of 70% of the liver during 10 min of IR. CF102 reduced the levels of liver enzymes following IR injury. A higher regeneration rate in the CF102 treatment group was observed compared with the control group, suggesting that CF102 had a positive effect on the proliferation of hepatocytes following hepatectomy. CF102 had a protective effect on the liver of Wistar rats subsequent to IR injury during hepatectomy. This may be due to an anti inflammatory and anti-apoptotic effect mediated by the A3AR. PMID- 27666665 TI - An attention account of neural priming. AB - Repetition priming of familiar stimuli (e.g., objects) produces a decrease in visual cortical activity for repeated versus novel items, which has been attributed to more fluent processing for repeated items. By contrast, priming of unfamiliar stimuli (e.g., abstract shapes) produces an increase in visual cortical activity. The mechanism for priming-related increases in activity for repeated unfamiliar stimuli is unknown. We hypothesised that such increases in activity may reflect attentional allocation to these items. We tested this hypothesis using a priming-spatial attention paradigm. During Phase 1 of Experiment 1, participants viewed unfamiliar abstract shapes and familiar objects. During Phase 2, participants identified target letters (S or H). Each target letter was preceded by a non-informative shape or object cue that was repeated (from Phase 1) or novel in the same (valid) or opposite (invalid) hemifield. In Experiment 2, we manipulated shape familiarity by presenting shapes once or six times during Phase 1. For both experiments, at valid locations, target identification accuracy was higher following repeated versus novel unfamiliar item cues and lower following repeated versus novel familiar item cues. These findings support our hypothesis that priming-related increases in visual cortical activity for repeated unfamiliar items may, in part, reflect attentional allocation. PMID- 27666666 TI - Simultaneous steering and imaging of magnetic particles using MRI toward delivery of therapeutics. AB - Magnetic resonance navigation (MRN) offers the potential for real-time steering of drug particles and cells to targets throughout the body. In this technique, the magnetic gradients of an MRI scanner perform image-based steering of magnetically-labelled therapeutics through the vasculature and into tumours. A major challenge of current techniques for MRN is that they alternate between pulse sequences for particle imaging and propulsion. Since no propulsion occurs while imaging the particles, this results in a significant reduction in imaging frequency and propulsive force. We report a new approach in which an imaging sequence is designed to simultaneously image and propel particles. This sequence provides a tradeoff between maximum propulsive force and imaging frequency. In our reported example, the sequence can image at 27 Hz while still generating 95% of the force produced by a purely propulsive pulse sequence. We implemented our pulse sequence on a standard clinical scanner using millimetre-scale particles and demonstrated high-speed (74 mm/s) navigation of a multi-branched vascular network phantom. Our study suggests that the magnetic gradient magnitudes previously demonstrated to be sufficient for pure propulsion of micron-scale therapeutics in magnetic resonance targeting (MRT) could also be sufficient for real-time steering of these particles. PMID- 27666667 TI - Tunable potential well for plasmonic trapping of metallic particles by bowtie nano-apertures. AB - In this paper, the tunable optical trapping dependence on wavelength of incident beam is theoretically investigated based on numerical simulations. The Monte Carlo method is taken into account for exploring the trapping characteristics such as average deviation and number distribution histogram of nanoparticles. It is revealed that both the width and the depth of potential well for trapping particles can be flexibly adjusted by tuning the wavelength of the incident beam. In addition, incident wavelengths for the deepest potential well and for the strongest stiffness at bottom are separated. These phenomena are explained as the strong plasmon coupling between tweezers and metallic nanoparticles. In addition, required trapping fluence and particles' distributions show distinctive properties through carefully modifying the incident wavelengths from 1280 nm to 1300 nm. Trapping with lowest laser fluence can be realized with 1280 nm laser and trapping with highest precision can be realized with 1300 nm laser. This work will provide theoretical support for advancing the manipulation of metallic particles and related applications such as single-molecule fluorescence and surface enhanced Raman spectroscopy. PMID- 27666668 TI - Challenges and opportunities in global mental health: a perspective from WHO. AB - This paper enumerates and briefly discusses WHO's recent contributions to global mental health and the current challenges and opportunities in this area. It briefly discusses response to diversity across countries and communities, the need for innovations and global exchange of information, evidence and knowledge and raises issues like psychological interventions and human rights related to mental health. PMID- 27666669 TI - Psychosocial intervention for carers of people with dementia: What components are most effective and when? A systematic review of systematic reviews. AB - BACKGROUND: Psychosocial interventions for carers of people with dementia are increasingly recognized as playing an important role in dementia care. We aim to systematically review the evidence from existing systematic reviews of psychosocial interventions for informal carers of people with dementia. METHODS: Thirty-one systematic reviews were identified; following quality appraisal, data from 13 reviews, rated as high or moderate quality, were extracted. RESULTS: Well designed, clearly structured multi-component interventions can help maintain the psychological health of carers of people with dementia and delay institutionalization of the latter. To be most effective, such interventions should include both an educational and a therapeutic component; delivery through a support group format may further enhance their effectiveness. CONCLUSIONS: Successful translation of evidence into practice in this area remains a challenge. Future research should focus on determining the most cost-effective means of delivering effective multi-component interventions in real-world settings; the cost-effective potential of technology-based interventions is considerable. PMID- 27666670 TI - Removal of emerging perfluorooctanoic acid and perfluorooctane sulfonate contaminants from lake water. AB - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the major polyfluoroalkyl substances (PFASs) contaminating global water environment. This study investigated the efficiency of granular activated carbon (GAC), ultrafiltration (UF) and nanofiltration (NF) treatment for removing PFOS and PFOA contaminants from lake water. NF gave greater removal of all contaminant types (in terms of organic matter, PFOS and PFOA) than GAC treatment which in turn was greater than UF treatment. The lower removal by UF was due to larger pore size of the membrane compared to the size of the target contaminants. For all treatment processes, lower pH (4) in the feedwater showed greater rejection of the organics and selected PFASs. This was likely due to increase in the electrostatic repulsion between solute and sorbent. It could be observed that on increasing the concentration of organics in the feed solution, the rejection of PFOA/PFOS decreased which was due to competition between organics and PFOS/PFOA for binding sites on the membrane/activated carbon surface. It was also noted that protein content led to greater influence for lower rejection of the PFOA/PFOS than carbohydrate or DOC content. This study demonstrated the potential use of membrane processes for removing emerging persistent organic pollutant removal from lake water. PMID- 27666671 TI - Integrating occurrence and detectability patterns based on interview data: a case study for threatened mammals in Equatorial Guinea. AB - Occurrence models that account for imperfect detection of species are increasingly used for estimating geographical range, for determining species landscape relations and to prioritize conservation actions worldwide. In 2010, we conducted a large-scale survey in Rio Muni, the mainland territory of Equatorial Guinea, which aimed to estimate the probabilities of occurrence and detection of threatened mammals based on environmental covariates, and to identify priority areas for conservation. Interviews with hunters were designed to record presence/absence data of seven species (golden cat, leopard, forest elephant, forest buffalo, western gorilla, chimpanzee and mandrill) in 225 sites throughout the region. We fitted single season occupancy models and recently developed models which also include false positive errors (i.e. species detected in places where it actually does not occur), which should provide more accurate estimates for most species, which are susceptible to mis-identification. Golden cat and leopard had the lowest occurrence rates in the region, whereas primates had the highest rates. All species, except gorilla, were affected negatively by human settlements. The southern half of Rio Muni showed the highest occurrence of the species studied, and conservation strategies for ensuring the persistence of threatened mammals should be focused on this area. PMID- 27666672 TI - Microbial Characteristics of Peri-Implantitis: A Case-Control Study. AB - BACKGROUND: The aim of this case-control study is to compare oral microbiologic characteristics of patients with healthy peri-implant conditions and patients with peri-implantitis and to explore the influence of various patient- and implant-related factors on microbiologic characteristics. METHODS: Peri-implant submucosal microbial samples were collected from 85 patients with peri implantitis (cases) and from 69 patients with only implants with healthy peri implant conditions (controls). Samples were analyzed using culturing techniques. Multivariable logistic regression was used to explore the association of disease status and various patient- and implant-related factors (sex, patient age, smoking, number of remaining teeth, percentage of teeth with bone loss, implant function time, implant surface, and presence of plaque) with microbiologic characteristics. RESULTS: Peri-implant disease status was significantly associated with the submucosal presence of Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythia (Tf), and Fusobacterium nucleatum (Fn). The association with disease status was most obvious for Pi (odds ratio [OR]: 15.1; 95% confidence interval [CI]: 5.1 to 45.3) and Tf (OR: 13.3; 95% CI: 5.4 to 32.5). The prevalence of Aggregatibacter actinomycetemcomitans and Staphylococcus species was very low. CONCLUSIONS: The periodontal pathogens Pg, Pi, Tf, and Fn are associated with peri-implantitis. A. actinomycetemcomitans and Staphylococcus species do not seem to play an important role in peri-implantitis. PMID- 27666673 TI - Decrease of Pericytes is Associated With Liver Disease Caused by Ligature-Induced Periodontitis in Rats. AB - BACKGROUND: Damage caused by periodontitis not only affects periodontal tissues, but also increases the severity of various illnesses such as rheumatoid arthritis, diabetes, and liver diseases. The aim of this study is to investigate the association between induced periodontitis and damage caused through its systemic effects on the liver. METHODS: Twenty rats were divided into two groups: control and periodontitis. The following parameters were evaluated: gingival bleeding index (GBI), probing depth (PD), myeloperoxidase (MPO) activity, alveolar bone loss (ABL) for periodontal tissues; histopathologic examination of gingival and liver tissues; immunohistochemistry to cells positive for neural/glial antigen 2 (NG2) expressed in hepatic pericytes, glutathione (GSH), and malondialdehyde (MDA) concentrations in liver; and serum levels of alanine aminotransferase and aspartate aminotransferase. RESULTS: GBI, PD, MPO, ABL, and histopathologic examinations demonstrated the development of periodontitis. There was a significant increase in microvesicular steatosis accompanied by a marked reduction in NG2+ pericytes in the periodontitis group compared with the control group. The periodontitis group had significantly lower GSH and higher MDA concentration in the liver compared with the control group. CONCLUSIONS: The present study results link the systemic effects of induced periodontitis with changes in hepatic tissues such as microvesicular steatosis, likely caused by an increase in oxidative stress and lipid peroxidation. The findings from the present study implicate an association between a decrease of pericytes and liver disease caused by ligature-induced periodontitis in rats. PMID- 27666674 TI - Mechanism of metamifop inhibition of the carboxyltransferase domain of acetyl coenzyme A carboxylase in Echinochloa crus-galli. AB - Acetyl-coenzyme A carboxylase (ACCase) plays crucial roles in fatty acid metabolism and is an attractive target for herbicide discovery. Metamifop is a novel ACCase-inhibiting herbicide that can be applied to control sensitive weeds in paddy fields. In this study, the effects of metamifop on the chloroplasts, ACCase activity and carboxyltransferase (CT) domain gene expression in Echinochloa crus-galli were investigated. The results showed that metamifop interacted with the CT domain of ACCase in E. crus-galli. The three-dimensional structure of the CT domain of E. crus-galli ACCase in complex with metamifop was examined by homology modelling, molecular docking and molecular dynamics (MD) simulations. Metamifop has a different mechanism of inhibiting the CT domain compared with other ACCase inhibitors as it interacted with a different region in the active site of the CT domain. The protonation of nitrogen in the oxazole ring of metamifop plays a crucial role in the interaction between metamifop and the CT domain. The binding mode of metamifop provides a foundation for elucidating the molecular mechanism of target resistance and cross-resistance among ACCase herbicides, and for designing and optimizing ACCase inhibitors. PMID- 27666675 TI - Emergence of global scaling behaviour in the coupled Earth-atmosphere interaction. AB - Scale invariance property in the global geometry of Earth may lead to a coupled interactive behaviour between various components of the climate system. One of the most interesting correlations exists between spatial statistics of the global topography and the temperature on Earth. Here we show that the power-law behaviour observed in the Earth topography via different approaches, resembles a scaling law in the global spatial distribution of independent atmospheric parameters. We report on observation of scaling behaviour of such variables characterized by distinct universal exponents. More specifically, we find that the spatial power-law behaviour in the fluctuations of the near surface temperature over the lands on Earth, shares the same universal exponent as of the global Earth topography, indicative of the global persistent role of the static geometry of Earth to control the steady state of a dynamical atmospheric field. Such a universal feature can pave the way to the theoretical understanding of the chaotic nature of the atmosphere coupled to the Earth's global topography. PMID- 27666677 TI - Markers of oxidative stress in obese men with and without hypertension. AB - OBJECTIVES: The aim of our study was to investigate if the 24-hour excretion of the urinary markers for oxidative stress to DNA and RNA, measured as 8-oxo-7,8 dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydro-guanosine (8-oxoGuo), respectively, were increased in obese individuals with or without hypertension compared to lean controls. METHODS: A total of 63 obese hypertensive men (obeseHT), 40 obese normotensive men (obeseNT) and 27 lean normotensive men (leanNT) were included in the study. Body mass index (BMI) was between 20.0 and 24.9 kg/m2 in leanNT participants and >=30 kg/m2 in obese participants. Hypertension was defined as a mean 24-hour systolic ambulatory blood pressure (AMBP) >= 130 mmHg or a mean 24-hour diastolic AMBP >=80 mmHg and normotension as mean 24-hour AMBP <130/80 mmHg. Twenty-four hour urinary 8-oxoGuo and 8-oxodG excretion (nmol/24 h) were measured by a validated liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS). RESULTS: Urinary 8-oxoGuo excretion was (median and [interquartile range]) 30.8 [27.8-32.2] nmol/24 h in leanNT, 36.8 [31.3-40.2] nmol/24 h in obeseNT and 40.6 [31.7-48.5] nmol/24 h in obeseHT. The difference was statistically significant (p = .002) and post hoc tests showed a significant difference between leanNT and obeseHT (p = .001) as well as obeseNT (p = .002), whereas the two obese groups did not differ (p = .6). No statistically significant differences in 8-oxodG concentrations were observed between the three groups (p = .3). CONCLUSION: The measurement of urinary excretion of 8-oxoGuo suggests that obesity in men, but not hypertension, is associated with increased oxidative damage to RNA. PMID- 27666678 TI - Erratum: Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells. PMID- 27666676 TI - Myeloid Cell-Specific Lipin-1 Deficiency Stimulates Endocrine Adiponectin-FGF15 Axis and Ameliorates Ethanol-Induced Liver Injury in Mice. AB - Lipin-1 is a phosphatidate phosphohydrolase (PAP) required for the generation of diacylglycerol during glycerolipid synthesis, and exhibits dual functions in the regulation of lipid metabolism. Lipin-1 has been implicated in the pathogenesis of alcoholic liver disease (ALD). In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model. Utilizing the Gao-binge ethanol feeding protocol, matched mLipin-1KO mice and littermate loxP control (WT) mice were pair-fed with either an ethanol-containing diet or an ethanol-free diet (control). Surprisingly, deletion of lipin-1 in myeloid cells dramatically attenuated liver inflammatory responses and ameliorated liver injury that would normally occur following the ethanol feeding protocol, but slightly exacerbated the ethanol induced steatosis in mice. Mechanistically, myeloid cell-specific lipin-1 deficiency concomitantly increased the fat-derived adiponectin and ileum-derived fibroblast growth factor (FGF) 15. In concordance with concerted elevation of circulating adiponectin and FGF15, myeloid cell-specific lipin-1 deficiency diminished hepatic nuclear factor kappa B (NF-kappaB) activity, limited liver inflammatory responses, normalized serum levels of bile acids, and protected mice from liver damage after ethanol challenge. Our novel data demonstrate that myeloid cell-specific deletion of lipin-1 ameliorated inflammation and alcoholic hepatitis in mice via activation of endocrine adiponectin-FGF15 signaling. PMID- 27666679 TI - Effects of dietary supplementation of rumen-protected folic acid on rumen fermentation, degradability and excretion of urinary purine derivatives in growing steers. AB - The present experiment was undertaken to determine the effects of dietary addition of rumen-protected folic acid (RPFA) on ruminal fermentation, nutrient degradability, enzyme activity and the relative quantity of ruminal cellulolytic bacteria in growing beef steers. Eight rumen-cannulated Jinnan beef steers averaging 2.5 years of age and 419 +/- 1.9 kg body weight were used in a replicated 4 * 4 Latin square design. The four treatments comprised supplementation levels of 0 (Control), 70, 140 and 210 mg RPFA/kg dietary dry matter (DM). On DM basis, the ration consisted of 50% corn silage, 47% concentrate and 3% soybean oil. The DM intake (averaged 8.5 kg/d) was restricted to 95% of ad libitum intake. The intake of DM, crude protein (CP) and net energy for growth was not affected by treatments. In contrast, increasing RPFA supplementation increased average daily gain and the concentration of total volatile fatty acid and reduced ruminal pH linearly. Furthermore, increasing RPFA supplementation enhanced the acetate to propionate ratio and reduced the ruminal ammonia N content linearly. The ruminal effective degradability of neutral detergent fibre from corn silage and CP from concentrate improved linearly and was highest for the highest supplementation levels. The activities of cellobiase, xylanase, pectinase and alpha-amylase linearly increased, but carboxymethyl cellulase and protease were not affected by the addition of RPFA. The relative quantities of Butyrivibrio fibrisolvens, Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes increased linearly. With increasing RPFA supplementation levels, the excretion of urinary purine derivatives was also increased linearly. The present results indicated that the supplementation of RPFA improved ruminal fermentation, nutrient degradability, activities of microbial enzymes and the relative quantity of the ruminal cellulolytic bacteria in a dose-dependent manner. According to the conditions of this experiment, the optimum supplementation level of RPFA was 140 mg/kg DM. PMID- 27666680 TI - Nutrient utilisation, growth performance and blood metabolites in Murrah buffalo calves (Bubalus bubalis) divergently selected for residual feed intake. AB - The aim of this study was to evaluate differences in efficiency of feed utilisation between buffalo calves with low and high residual feed intake (RFI) by comparing feed intake, nutrient digestibility, growth traits and blood metabolites. Eighteen male Murrah buffalo calves (aged 4-6 months; 70 +/- 1.0 kg body weight) were fed ad libitum with a total mixed ration for 120 d. Based on linear regression models involving dry matter intake (DMI), average daily gain (ADG) and mid-test metabolic body size, calves were assigned into low and high RFI groups. The RFI varied from -0.33 to +0.28 kg DM/d with an average RFI of 0.14 and 0.14 kg DM/d in low and high RFI calves, respectively. Calves had a mean DMI of 1.9 and 2.4 kg/d and an ADG of 0.5 and 0.6 kg/d in low and high RFI groups, respectively. Low RFI calves ate 19.0% less DM each day and required significantly less metabolisable energy for maintenance compared with high RFI calves (12.5 vs. 16.7 MJ/d). Nutrient digestibility and nitrogen balance did not differ among low and high RFI calves. In more efficient animals (low RFI calves) higher (p < 0.05) plasma level of growth hormone, insulin-like growth factor-1 (IGF-1), triiodothyronine (T3) and lower concentration of thyroxin hormone were detected. No significant differences in levels of insulin, hydroxyproline, plasma and urine creatinine, total protein and albumin between high and low RFI groups were found. Blood metabolites showed significant (p < 0.05) differences at initial and final stages of study in both groups. At final stage of study, RFI showed negative correlations with growth hormone, IGF-1, T3, urine creatinine and albumin. Low RFI buffalo calves are more efficient in feed utilisation and the differences in blood metabolites are probably due to differences in feed intake and body metabolism. PMID- 27666681 TI - Pea protein concentrate in diets for sharpsnout sea bream (Diplodus puntazzo): effects on growth and health status. AB - Four diets for sharpsnout sea bream juveniles (14 g body weight) with four levels of air-processed pea protein concentrate (PPC) (0, 160, 320 and 487 g/kg diet) were tested in triplicate. The experimental diets were isonitrogenous (43% crude protein) and isolipidic (19% ether extract) and the fish were fed to satiation twice a day. After 125 d, fish growth was diminished by the inclusion of PPC. Feed conversion did not show significant differences in any treatment. Neither the body analyses nor the protein and individual essential amino acid retention efficiencies were affected by the inclusion of PPC in the diet. However, histological gut examinations revealed noticeable differences. Fish fed the diet with the highest inclusion level of PPC presented the longest villous length and the most goblet cells, and the width of the lamina propria increased in the anterior intestine. Although no negative changes in nutritive parameters were detected, these alterations might affect nutrient transport, with negative consequences for fish growth. It was concluded that the PPC in the amounts tested here is an inappropriate substitute for fishmeal in diets for sharpsnout sea bream juveniles. PMID- 27666685 TI - [Osteoporosis in chronic obstructive pulmonary disease.] AB - Chronic Obstructive Pulmonary Disease(COPD)is characterized by persistent airflow limitation that is associated with chronic inflammatory process caused by inhaled noxious particles such as cigarette smoke. COPD involves not only the lungs but also extrapulmonary abnormalities as systemic effects. Osteoporosis is one of major comorbidities in COPD, and is often under-diagnosed. Osteoporosis in COPD is associated with various factors including smoking, decreased body mass index, and systemic inflammation. It should be recognized that COPD is a risk factor for osteoporosis and bone fracture, and early diagnosis and management for both COPD and osteoporosis are important. PMID- 27666683 TI - MicroRNA-210 promotes cancer angiogenesis by targeting fibroblast growth factor receptor-like 1 in hepatocellular carcinoma. AB - Hypoxia drives cancer to become more aggressive, particularly angiogenesis, and the corresponding mechanisms still need to be further investigated. In hepatocellular carcinoma (HCC), the master hypoxia-induced microRNA (miRNA) miR 210 is upregulated in HCC and participates in HCC progression, but its roles in hypoxia-induced HCC angiogenesis are still unknown. Moreover, the correlation between miR-210 expression and HCC clinical progression also needs elucidation. In the present study, we found that miR-210 expression was progressively increased from normal liver and adjacent non-tumor tissues, to incipient and advanced tumor tissues. In HCC patients, high miR-210 expression was significantly correlated with poor prognosis, both tumor-free survival and overall survival. Moreover, miR-210 expression in HCC was significantly positively correlated with microvascular density. Both in vitro and in vivo studies determined that miR-210 promoted HCC angiogenesis, and the corresponding mechanism was identified to be the direct targeting and inhibition of fibroblast growth factor receptor-like 1 (FGFRL1) expression. Thus, we suggest a new prognosis predictor for HCC patients, and determined the roles of hypoxic miR-210 in HCC angiogenesis. PMID- 27666684 TI - [Epidemiology of respiratory diseases and osteoporosis.] AB - A large scale of epidemiological studies demonstrated that osteoporosis risk was about 1.5 times higher and fracture risk was 1.2-1.8 times higher among COPD patients. In COPD, risk factors for fracture have been reported to be severity of the COPD and use of bronchodilator in addition to ordinal risk factors for the fracture such as age, previous fracture, smoking, usage of glucocorticoid and others. There were inconsistent results of the relationship between sleep apnea and low bone mass. The relationship was found between sleep apnea and fall and non-spin fracture risk. PMID- 27666686 TI - [Obstructive sleep apnea syndrome(OSAS)and bone.] AB - Obstructive sleep apnea syndrome(OSAS)is a sleep disorder characterized by repetitive upper airway collapse during sleep, causing frequent hypoxia and sleep disturbance. Known risk factors of OSAS include obesity, male sex and smoking. OSAS has been linked to various comorbidities such as hypertension, cardiovascular diseases and diabetes. Recent evidence also indicates that OSAS is associated with vitamin D insufficiency, increased bone resorption and bone loss. Thus, although increased fracture rate has not been demonstrated, OSAS is now recognized as a risk factor of osteoporosis. This review will summarize the recent reports about bone metabolic abnormalities in OSAS. PMID- 27666687 TI - [Sarcopenia and osteoporosis in pulmonary disease.] AB - Chronic obstructive pulmonary disease(COPD)is a progressive lung disease and its prevalence increases with age. Elderly patients with COPD are known to be at increased risk of sarcopenia and osteoporosis, and this multimorbidity adversely affects progression and prognosis of COPD in parallel. Systemic inflammatory processes and serum biomarkers including cytokines and C-reactive protein might be involved in the underlying pathphyisoplogy for systemic manifestations and multimorbidity of respiratory diseases. In this review, recent insights in the association between respiratory diseases and sarcopenia are introduced, based on the pathophysiology and therapeutic implication of systemic inflammation and age related muscle wasting. PMID- 27666688 TI - [Bone turnover and bone structure in clinical animal models of COPD.] AB - The features of chronic obstructive pulmonary disease(COPD)are chronic inflammatory and emphysema changes in the lungs by long-term cigarette smoke(CS)exposure. Osteoporosis is an important systemic comorbidity of COPD. Severe emphysema and low body mass index(BMI)are independent risk factors for low bone mineral density in COPD patients. However the pathophysiologic mechanisms underlying emphysema and osteoporosis have not been fully elucidated. An established mouse model of CS-induced emphysema with decrease body weight and bone mineral density is important for investigating the cause of osteoporosis in COPD patients. PMID- 27666689 TI - [Semaphorin and osteoporosis.] AB - Although Semaphorins were originally identified as neuronal axon guidance molecules, recent research has revealed the functions of Semaphorins in many organs, tissues and cells. Among Semaphorin family members, Semaphorin 3A(Sema3A)and Sema4D are highly expressed in bone cells and play critical roles in the regulation of bone homeostasis. Other semaphorins and their receptors are also shown to be involved in bone metabolism. In contrast, the function of Semaphorins expressed in lung is not well understood althogh many of Semaphorins are highly expressed in lung among various tissues examined. As growing evidence reveals that the link between chronic obstructive pulmonary disease(COPD)and osteoporosis, the crosstalk between bone and lung through Semaphorin signaling should be investigated. PMID- 27666690 TI - [Hypoxemia and Osteoporosis-Possible roles of HIF1alpha on Respiratory disease related Osteoporosis-.] AB - Osteoporosis is a disease characterized by increased risks for bone fragility fractures, and is caused by various factors such as aging and menopause. Increase in the number of osteoporosis patients becomes a big concern in the developed countries. Recently, the mechanisms underlying postmenopausal osteoporosis development were being clarified, and several diseases such as respiratory diseases and diabetes were reportedly caused secondary osteoporosis. HIF1alpha was demonstrated required for osteoclast activation and bone loss in postmenopausal osteoporosis women. However, the roles of HIF1alpha on respiratory disease-related osteoporosis development remained to be elucidated. PMID- 27666691 TI - [Bone quality in COPD.] AB - Chronic obstructive pulmonary disease(COPD)is a chronic inflammatory disease associated with an increase of fracture risk. Bone strength is determined by bone mass and quality.Bone quality is thought to encompass the structural and material properties of bone. Bone collagen crosslinking plays important roles in bone strength. The quantitative and qualitative deterioration of lysyl oxidase control and non enzymatic cross-links(advanced glycation end products, AGEs, pentosidine)of collagen in patients with osteoporotic femoral neck fracture and diabetes, and COPD might be affected by increased oxidative stress and glycation. PMID- 27666692 TI - [Smoking & Bone.] AB - Smoking is associated with decreased bone mineral density(BMD)and increased fracture risk. Conversely, smoking cessation results in BMD gain and decreased fracture risk, suggesting that smoking-induced bone metabolic changes are partially reversible. However, the mechanism of bone fragility induced by smoking is unknown. Meta-analyses have shown that aberrant PTH-vitamin D axis may affect bone metabolism in smokers. Previous animal studies have also reveled that nicotine, one of the major toxic substances of cigarettes, negatively regulates bone formation. This brief review will summarize recent studies on the effects of smoking on bone metabolism, including our recent results evaluating bone metabolic changes after smoking cessation. PMID- 27666693 TI - [Reduced ADL, QOL and musculoskeletal dysfunction associated with respiratory disease.] AB - Chronic respiratory disease, such as chronic obstructive pulmonary disease(COPD)continues to cause a heavy health and economic burden in the world. Lower-limb muscle dysfunction is a prominent and major extrapulmonary features in individuals with moderate-to-very severe COPD and has important clinical implications, such as reduced exercise tolerance, activity of daily living(ADL), health related quality of life(HRQOL)and even survival. Osteoporosis is also an important systemic feature of COPD. Osteoprotic fracture cause many symptoms and complications, including the impairment of ventilation, and create a heavy economic burden. Comprehensive treatments(drug medication and non-drug treatment)for these impairments, such as pulmonary rehabilitation, are recommended. Pulmonary rehabilitation improves dyspnea, exercise capacity, ADL, and HRQOL, each of which is recognized predictors of mortality. PMID- 27666694 TI - [Steroids-induced osteoporosis due to the treatment for Pulmonary diseases.] AB - Corticosteroids are key medications to treat pulmonary diseases. A variety of medications, doses, administration route, and duration of corticosteroids were chosen for each of pulmonary diseases. Although corticosteroids are potent medications, they often cause serious adverse effects such as osteoporosis, diabetes, and immunosuppression. Thus, physicians have to properly assess the risk of adverse effects to prevent them. In this review, we discuss the risk of osteoporosis by corticosteroids that are prescribed for pulmonary diseases. Inhaled corticosteroids are not serious risk factors of osteoporosis. If systemic corticosteroids are planned to be administrated in the prednisolone equivalent dosage of 5 mg/day or more for three months or longer, risk of bone fracture have to be assessed regardless of the primary pulmonary disease. If necessary, prophylactic agent such as bisphosphonates should be prescript. PMID- 27666695 TI - [A comprehensive therapeutic strategy for osteoporosis in respiratory diseases.] AB - Many respiratory diseases including COPD are systemic disorders as well as pulmonary disorders. The diseases predominantly occurred in older peoples in advanced countries. Comprehensive therapeutic strategy including bronchodilators and systemic rehabilitation is necessary for maintenance of stable condition of pulmonary diseases. Importantly, physical activity is a key factor for the prognosis in the diseases, in this point, bone function and muscle function should be improved by the appropriate treatment. The regular assessment of bone density and muscle function are necessary for better prognosis of COPD patients. PMID- 27666696 TI - [Medical treatment for osteoporosis with pulmonary disorders-from a viewpoint of an endocrinologist-.] AB - Today, we can treat osteoporotic patients with multiple drugs of various mechanisms and in various forms. Nevertheless, there exist few clinical evidences that exhibit an efficacy of an anti-osteoporotic drug on osteoporosis with pulmonary disorders, including asthma, COPD and OSAS. We should use drugs for osteoporotic patients with pulmonary disorders in accordance with a guideline on the management and treatment of glucocorticoid-induced osteoporosis or a guideline on the management and treatment of osteoporosis, according to whether they are treated by glucocorticoid or not. PMID- 27666699 TI - [The model of specialized training for diagnosis and treatment in thyroid cancer]. PMID- 27666698 TI - Real-time encoding and compression of neuronal spikes by metal-oxide memristors. AB - Advanced brain-chip interfaces with numerous recording sites bear great potential for investigation of neuroprosthetic applications. The bottleneck towards achieving an efficient bio-electronic link is the real-time processing of neuronal signals, which imposes excessive requirements on bandwidth, energy and computation capacity. Here we present a unique concept where the intrinsic properties of memristive devices are exploited to compress information on neural spikes in real-time. We demonstrate that the inherent voltage thresholds of metal oxide memristors can be used for discriminating recorded spiking events from background activity and without resorting to computationally heavy off-line processing. We prove that information on spike amplitude and frequency can be transduced and stored in single devices as non-volatile resistive state transitions. Finally, we show that a memristive device array allows for efficient data compression of signals recorded by a multi-electrode array, demonstrating the technology's potential for building scalable, yet energy-efficient on-node processors for brain-chip interfaces. PMID- 27666700 TI - [Analyses of prognostic factors relevant to acute low-tone sensorineural hearing loss]. AB - Objective: To investigate the prognostic factors relevant to acute low-tone sensorineural hearing loss (ALHL). Methods: 196 adult ALHL patients, including 82 males and 114 females with mean age of (43.1+/-14.3)years old were included. All patients received the same therapy and were evaluated the curative effect. To evaluate the impact factors on the prognosis of hearing, inclusive of age, gender, time delay before the first visit, degree of deafness, vestibular function, electrocochleogram, and the serum levels of thyroxines by SPSS 18.0 software. Results: Of those 196 patients with ALHL, 124(63.3%) were recovery, 5(2.6%) were excellent better, 42(21.4%) were better, and 25 (12.8%) were poor, with a total effective rate of 87.2%. Among 15 (12.1%) who recurred the hearing loss, 2 developed into Meniere's disease during the follow-up. The mean age of patients with poor hearing effect was significantly older than that of other patients (P<0.05). No relativity was found between gender and hearing curative effect. There existed a statistical difference in total effective rate among subjects with different histories (P<0.05). In addition, the recovery rate was significantly different between groups, i. e., the course of disease was less than 14 days, between 14 days and 6 months, and between 6 months and 2 years (P<0.05). There was no statistical significance in total effective rate among different degrees of deafness (P>0.05). However, in term of the recovery rate, the difference was statistical significance (P<0.05). The recovery rate in patients with mild hearing loss was higher than that in middle or heavy hearing loss (both P<0.05). Among patients with mild deafness, the recovery rate in patients whose history was less than 3 months was significantly higher than that more than 3 months (P<0.05). For moderate deafness patients, the recovery rate in patients whose history was less than 7 days was significantly higher than that more than 1 month (P<0.05). There were statistical differences in hearing effect of 130 (66.3%) patients with abnormal vestibular function in comparison to that with normal vestibular function (chi2=15.1, P<0.05). There were 17(8.7%) patients with abnormal electrocochleogram combined with abnormal vestibular function, and the hearing effects were all poor. There were 45 (23.0%) patients with abnormal thyroxine levels in serum, which was significant higher than that in health adults of 5.9%(chi2=7.26, P<0.01). There was no significant difference in hearing prognosis between patients with abnormal and normal thyroxine levels (chi2=2.51, P>0.05). Conclusions: With respect to ALHL, the hearing effect is associated significantly with the history. The severity of hearing loss is negative prognostic factor for hearing recovery. Age, vestibular function, and electrocochleogram might predict hearing recovery. Gender and thyroxine levels couldn't predict the hearing prognosis, although there is a high incidence rate in patients with ALHL. PMID- 27666701 TI - [Characteristics of cervical vestibular evoked myogenic potential in different test positions]. AB - Objective: To investigate the characteristics of cervical vestibular evoked myogenic potential (cVEMP) of normal youth with different test positions, to study the relationship between test positions and test parameters, and to explore the suitable test position for clinical practice. Methods: Fifty healthy young volunteers (25 males, 25 females, 100 ears) were enrolled in this study. Two test positions were used, including sitting with the head turned away from the test (SIT) and supine with the head held straight up (SUP). The derivation rate, latency and amplitude were analyzed. Results: The derivation rates of both SIT and SUP were 100%. The VEMP threshold in SIT was (93.5+/-4.3)dBnHL. The latency of P1 and N2 in SIT was longer than that in SUP, with significant different (P< 0.05), the amplitude of P1-N2 in SIT was less than that in SUP, with significant different (P< 0.05). Regarding to the latency of P1 and N2 in SIT, the left was longer that right, with (P=0.013) and (P=0.015) respectively. The latency in SUP between sides was not significant (P>0.05). The amplitude ratio and asymmetry in SIT were more obvious than in supine position (P=0.009 and 0.016). In SIT position the P1-N2 amplitude in males was larger than in females, with significant difference (P=0.031); In SUP position the P1-N2 amplitude in males was less than in females, with significant difference (P=0.043). Conclusion: The cVEMP can be affected by the different test positions, it is recommended to select a more suitable test position according to the condition of the subject and the purpose of the test. PMID- 27666702 TI - [Psychopathological characteristics in patients with deviation of nasal septum: a preliminary analysis]. AB - Objective: To investigate the psychopathological characteristics in patients with deviation of nasal septum. Methods: Between May 2015 and December 2015, fourty four patients with deviated nasal septum and 37 patients with vocal cord polyp as control were included in this study. Psychological characteristics were evaluated by a series of questionnaire instruments including symptom checklist-90 (SCL-90), self-rating depression scale (SDS) and self-rating anxiety scale (SAS). Visual analogue scale (VAS) and rhinomanometry through front nostril were used to evaluate nasal symptom. The correlation between psychological characteristics and nasal symptom was evaluated. SPSS 20.0 software was used to analyze the data. Results: The SCL-90 score in nasal septal deviation group was 130.4+/-48.3. The total score and total average score of SCL-90 had no significant difference between nasal septal deviation group and the Chinese standard or control group(t value was 0.469, 0.112, 1.575, 1.564, respectively, all P>0.05). The scores of somatization, depression and anxiety factors in nasal septal deviation group were higher than control group (t value was 2.380, 2.133, 1.969, respectively, all P<0.05). The proportion of positive patients in these three factors between nasal septal deviation group and control group had significant differences (chi2 value was 11.585, 9.610, 5.429, respectively, all P<0.05). The scores of SDS and SAS in nasal septal deviation group were 46.0+/-10.6 and 43.0+/-10.2, which were higher than that in the Chinese standard and control group (t value was 5.342, 6.236, 1.476, 3.013, respectively, all P<0.05). There were 9 patients companying with depression or anxiety (20.5%, 20.5%, respectively) and 5 patients companying with depression and anxiety in nasal septal deviation group (11.4%). There were positive correlation not only between the scores of SDS and the depression factor of SCL-90 but also between the scores of SAS and the anxiety factor of SCL-90 (Z=0.415, P=0.005, Z=0.445, P=0.002, respectively). The scores of SDS and SAS had positive correlation (Z=0.392, P=0.008). The VAS score of nasal obstruction was 6.0+/-3.2. The rhinomanometry in inspiratory and expiratory phase were (0.202+/ 0.140) kPa.S/cm3 and (0.230+/-0.161) kPa.S/cm3. Besides the positive correlation between the rhinomanometry in inspiratory phase and SDS (Z=0.332, P=0.045), the psychological scores, including SCL-90 score, depression, anxiety factors score, SAS and SDS, had no correlation with VAS scores and rhinomanometry (r value was 0.030, -0.052, -0.026, 0.107, 0.185, 0.066, 0.160, 0.203, respectively, all P>0.05). Conclusions: High prevalence of depression and anxiety is found in patients with deviation of nasal septum. The SCL-90 score is consistent with SDS and SAS. Besides the positive correlation between the rhinomanometry in inspiratory phase and SDS, the psychological scores (SCL-90 score, depression, anxiety factors score, SAS and SDS) have no correlation with VAS score and rhinomanometry. PMID- 27666703 TI - [A comparison of pH<4 and pH<5 as thresholds for 24-hour pH monitoring in the diagnosis of laryngopharyngeal reflux]. AB - Objective: To evaluate the consistency between 24-hour pH monitoring, reflux symptom index(RSI) and reflux finding score(RFS) when using pH<4 or pH<5 as threshold for 24-hour pH monitoring in the diagnosis of laryngopharyngeal reflux. Methods: Patients who presented with suspicious laryngopharyngeal reflux between February 2014 and December 2015 were included in this study. pH<4 and pH<5 reflux episodes, RSI and RFS were collected. The consistency between 24-hour pH monitoring and scale results were analyzed when pH<4 or pH<5 as threshold respectively. The sensitivity and specificity of 24-hour pH monitoring were calculated separately. Results: Median number(M[P25, P75, P95]) of reflux events were 0 [0, 3.0, 5.5] when using pH<4 as pathological threshold and 0 [0, 4.0, and 8.5] using pH<5 as pathological threshold. Laryngopharyngeal reflux was determined in 34.5% patients depending on 24-hour pH monitoring when pH<4 was used as threshold, chi-square revealed medium consistency (kappa=0.483) between pH monitoring and scale result. If pH<5 was used as threshold, 41.8% patients were detected with laryngopharyngeal reflux, and the consistency of pH monitoring and scale result was medium(kappa=0.540). With RSI and RFS for reference, the sensitivity and specificity of 24-hour pH monitoring were 54.7% and 93.4% respectively when pH<4 was used as threshold. If pH<5 was used as threshold, the sensitivity and specificity of 24-hour pH monitoring were 65.6% and 91.3% respectively. Conclusions: Compared with pH<4 as pathological threshold, the consistency of pH monitoring and scale results was a little better using pH<5 as pathological threshold. PMID- 27666705 TI - [Simultaneous repairing defects of orbital floor and palate with the modified temporalis muscle flap after the maxillectomy]. AB - Objective: To evaluate the outcome of one-stage reconstruction of maxillary and orbital defects with modified temporalis muscle flap (TMF) following the removal of malignant neoplasms. Methods: In this retrospective study, 15 patients underwent the reconstruction of defects of orbital floor and palate after maxillectomy for malignant tumor were included from June 2008 to June 2014. The modified temporalis muscle flap was used to repair the defects after surgery, and functional outcomes were analyzed. Results: All the patients were followed up for 12-81 months. Three cases of them received preoperative radiotherapy and 12 cases underwent postoperative radiotherapy. All flaps were survived. Epithelization of the tissues in oral and nasal cavity was completed in 4-6 weeks. Good functional reconstruction on swallowing and speaking functional results were achieved with maxillary and orbital reconstruction and no secondary deformity of external nose was observed. The eye positions in all cases were normal. Diplopia, diminution and loss of vision were not found. Conclusion: The modified TMF can be used for simultaneous reconstruction for the defects of orbital floor and palate after maxillectomy in patients whom free tissue flap can not be applied to, showing better cosmetic and functional results. PMID- 27666704 TI - [Preliminary application of Dx-pH monitoring system in laryngopharyngeal reflux disease]. AB - Objective: To summarize the application and significance of Dx-pH monitoring system in laryngopharyngeal reflux disease. Methods: Fifty-four patients who had symptoms of laryngopharyngeal reflux disease in our department from February to December in 2015 were retrospectively analyzed in this study. All patients were evaluated with reflux symptoms index(RSI), flexible laryngoscope and reflux finding score(RFS), and larygopharygeal Dx-pH monitoring. Results: Among all 54 patients, there were 26 patients whose Ryan score were positive(48.2%). The positive Ryan score mainly emerged when the patients were upright(24/26, 92.3%). Among 22 patients whose symptoms could not alleviate well by 8 weeks proton pump inhibitors treatment, there were 13 patients(59.1%) with positive Ryan scores. The Ryan scores were not in good accordance with RSI and RFS(kappa=-0.013). Conclusions: Although the results were not in good accordance with RSI/RFS, Dx-pH monitoring system could prove laryngopharyngeal reflux events in patients with laryngopharyngeal reflux disease and help physicians to diagnose. PMID- 27666706 TI - [Experimental study on substance P in the regulation of degranulation of cultured murine mast cells]. AB - Objective: To investigate the effect of interleukin-4 (IL-4) stimulation on the expression of FcepsilonRIalpha and NK-1R on mature mast cells(MC) cultured and differentiated from mouse bone marrow stem cells, and then to study if these MC also respond to substance P (SP) both in FcepsilonRIalpha and NK-1R dependent manners. Methods: Bone marrow cells were aseptically flushed from BALB/c mouse femurs into complete RPMI 1640, followed by culture with stem cell factor (SCF 100 MUg/L), IL-3 (15 MUg/L) and IL-4 (0, 10, 15, 20 and 25 MUg/L, respectively). The culture medium was changed once a week. The morphological changes of culture cells were observed under inverted microscope. After 4 weeks culture, the cells were collected and appraised by toluidine blue staining and flow cytometry. The expressions of surface CD117, FcepsilonRIalpha and NK-1R on these cells were detected by flow cytometry and Western blot. Bone marrow MC were activated with SP (0, 0.01, 0.1, 1.0 and 10 mg/L, respectively) for 30 min. The histamine released into the supernatant and stored in the protoplasm was quantified by enzyme linked immunosorbent assay (ELISA). The percentage of histamine release was calculated as a percent of total histamine content. Results: When different concentrations of IL-4 (0, 10, 15, 20, 25 MUg/L)were added into RPMI 1640, the positive rates of CD117 on MC surface were expressed as (94.8+/-1.3)%, (95.7+/ 2.5)%, (94.1+/-1.3)%, (96.6+/-1.0)%, and (96.6+/-1.1)%, respectively, and there was no significant difference among these groups (F=8.51, P>0.05). The positive rates of FcepsilonRIalpha were expressed as (81.5+/-2.6)%, (84.2+/-1.8)%, (91.8+/ 2.0)%, (91.6+/-1.6)%, and (93.0+/-2.6)%, respectively, and there was statistically increasing among these groups (F=15.76, P<0.05). Then MC were activated by SP (0, 0.01, 0.1, 1.0, 10 mg/L), histamine from 20 MUg/L IL-4 group were released (20.08+/-1.50)%, (32.76+/-2.99)%, (42.90+/-3.36)%,(50.21+/-1.29)%, (56.10+/-3.60)%, as similar as from 0 MUg/L IL-4 were (19.37+/-2.02), (19.50+/ 1.50), (21.77+/-1.91), (32.00+/-2.50), (33.56+/-1.25), there was significantly different when compared with each other (all P<0.05). Bone marrow MC were shown to have the highest expression of FcepsilonRIalpha and NK-1R in culture of 20 MUg/L IL-4 by the detection of Western blot, meanwhile these MC could be activated to degranulate by a lower concentration of SP (0.01 mg/L), with the release rate of histamine from MC showing a positive correlation with SP concentrations. On the other hand, MC with high expression of FcepsilonRIalpha and little expression of NK-1R cultured with 0 MUg/L IL-4, could also be activated by a much higher concentration of SP (1.0 mg/L). Conclusions: Bone marrow mast cells were shown to be successfully differentiated and to express NK 1R and FcepsilonRIalpha upon co-culture with SCF and IL-3 or SCF, IL-3 and IL 4.When IL-4 was added into RPMI 1640, bone marrow MC could highly produce FcepsilonRIalpha and NK-1R, thus building a better model of MC degranulation regulated by SP. And SP-controlled MC degranulation may be mediated through both FcepsilonRIalpha (immunologically) and NK-1R (non-IgE mediated or non immunologically) pathway. PMID- 27666707 TI - [Analysis of association of human 8-oxoguanine giycosylase 1 polymorphism with the susceptibility of laryngeal cancer]. AB - Objective: To study the association between human 8-oxoguanine giycosylase 1 (hOGG1) gene polymorphisms and the risk of laryngeal carcinoma. Methods: A total of 86 patients with laryngeal carcinoma treated in The Air Force General Hospital and the Bozhou People's Hospital of Anhui Province from Jan 2010 to Dec 2014 were included in experimental group, and 86 healthy adults were selected as control group. The hOGG1 gene polymorphisms of subjects in two group were detected with by polymerase chain reaction amplification and gene sequencing technology, the differences in hOGG1 gene polymorphisms between two groups were analyzed. Results: The frequencies of hOGG1 gene heterozygous type (Ser/Cys) and mutant type (Cys/Cys) in experimental group were higher than those in control group(P<0.05). Compared to individuals with hOGG1 gene Ser/Ser, individuals with hOGG1 gene Ser/Cys had a 2.97-fold increased risk of laryngeal carcinoma, and individuals with hOGG1 gene Cys/Cys had a 8.09-fold increased risk of laryngeal carcinoma. Stratified by smoking or not, it was found that the proportion of heterozygous type or mutant type in smokers was higher significantly than non smokers (P<0.05). Conclusion: Individuals with hOGG1 gene heterozygous type (Ser/Cys) or mutant type (Cys/Cys) have a higher risk of laryngeal carcinoma, with interaction between these gene types and smoking, and the gene types could be used as predictors for the occurrence of laryngeal carcinoma. PMID- 27666708 TI - [The study on the targets of the optical evoked auditory brainstem response on the cochlea of guinea pig stimulating by infrared laser]. AB - Objective: To identify the targets of the infrared laser stimulating on the cochlea of guinea pig which evoked auditory brainstem response (oABR), and explore the mechanisms of the infrared neurostimulation. Methods: A polished optical fiber with 200 MUm diameter (NA=0.22) was planted into the scala tympani of guinea pigs to stimulate the cochlea of both the normal hearing and acute deafened guinea pigs. The direction of the fiber distal was changed to radiate different regions of the scala tympani, recording the oABR respectively. Differences of energy thresholds and amplitudes of oABR between normal hearing and acute deafened animals was concerned, and different responses were recorded as the optical path of laser fiber being changed to investigate the targets of the infrared laser stimulation. Immunofluorescence was used to detect the changes of inner and outer hair cells, and spiral ganglion neurons 7 days post-deafening, to looking for the probable association with the oABR changes at the same stimulus. SPSS 18.0 software was used to analyze the data. Results: Inner and outer hair cells were damaged in basal and middle turn, butresidual hair cells were observed in apical turn.Only when the optical fiber pointed to Rosenthal's canal stimulated the spiral ganglion region directly could the oABR be evoked. No response was recorded while the fiber pointed to other directions. Conclusion: Infrared laser stimulates cochlea evoked oABR generats from the response of spiral ganglion directly, the spiral ganglion neurons are the target of infrared stimulation. PMID- 27666709 TI - [Analysis of the relevant factors for recurrent sudden sensorineural hearing loss]. AB - Objective: To investigate the possible factors related to recurrence and prognosis of sudden sensorineural hearing loss(SSNHL). Methods: Four hundred and ninety-five patients with unilateral sudden sensorineural hearing loss between January 2013 to April 2014 were analyzed retrospectively(34 patients lost to follow-up with a dropout rate of 6.87%). Twenty of the 495 patients were diagnosed as recurrent SSNHL and treated again in the same hospital. The data of the patients were summarized to analyze the related factors which might influence the recurrence and prognosis of SSNHL. Results: In the 20 patients with recurrent SSNHL, 19 had the second attack in same ear as the first attack, and the other one had in both ears. There were seven male patients, and thirteen female patients. Patients ranged in age from 24 to 77years, with a median age of 39.5 years. Types of hearing loss: low frequency in eight patients, high frequency in two patients, flat frequency in eight patients, total deafness in two patients, the types of the second attack in 17 patients were same as the first attack, only one patient was changed from total deafness to flat frequency, one case was changed from flat frequency to high frequency, one case changed from flat frequency to total deafness. The intervals between of the first attack time and the second attack time were 1-36 months with the median time of 3.5 months. After systemic oral and (or) transtympanic steroid treatment, recovered in three cases, effective in three cases and 14 cases invalid, the cure rate was 15%, and the total effective rate was 30%. There were statistically significant differences in the recovery rate(chi2=8.640, P<0.05) and the overall response rate(chi2=12.379, P<0.01)between the first and the second treatments. For the patients with vertigo and/or dizziness, with a history more than seven days, with hypertension or diabetes mellitus, and with a type of hearing loss except low frequency type, the treatment effect was invalid. The patients with hearing loss at low frequency had the best outcomes. The total effective rates were significant different between patients younger and old than 34 years old(P<0.05). There was no difference in the total effective rate between genders, and patients with or without tinnitus and/or aural fullness in the recurrent SSNHL(P>0.05). The recurrence rates of patients with various types of hearing loss were different(F=7.744, P<0.05), with a highest recurrence rate in patients with hearing loss at low frequency. Other factors such as gender, age, accompanied diseases (hypertension or diabetes mellitus), associated symptoms, interval from onset to treatment had no effects on the recurrence rate. Conclusions: Recurrence of SSNHL is more likely to be found in patients with hearing loss of low frequency and flat type. The prognosis of recurrent SSNHL is poorer than that of the first episode, and may be related to the age and type of hearing loss. PMID- 27666711 TI - [Otogenic intracranial abscess: clinical analyses of 4 cases]. PMID- 27666710 TI - [Application of transoral robotic surgery in pharyngolaryngeal tumour resection]. AB - Objective: To summarize clinical experience on application of transoral robotic surgery (TORS) in pharyngeal tumour resection. Methods: Six patients underwent TORS with da Vinci(r) surgical system in our department from November 2013 to July 2015 and their clinical data were analyzed retrospectively. Results: TORS was accomplished successfully in all 6 patients. The surgical field-exposed time ranged from 30 to 40 minutes with an average of 35 minutes. The operative time ranged from 30 to 130 minutes with an average of 72 minutes. The hospital stays ranged from 6 to 14 days with an average of 10 days, and recovery time for oral intake ranged from 2 to 10 days with an average of 6 days. During TORS, the mouth gag needed to be adjusted 2 to 5 times. Surgical blood loss ranged from 5 to 30 ml with an average of 15 ml. No complications occurred during or after operation. Postoperative pathological examination of incisal edge in patients with malignant tumors showed no residual tumor cell. The mean follow-up was 14 months with no recurrence. Conclusion: With proper indications, TORS possesses enormous value to the application in otolaryngology-head and neck surgery. PMID- 27666712 TI - [Sino-nasal sclerosis disease related to IgG4: a case report]. PMID- 27666713 TI - [A case report of subglottic cartilage tumor]. PMID- 27666714 TI - [Ectopic thymic cyst in thyroid: a case report]. PMID- 27666715 TI - [Angiosarcoma of the thyroid gland: a case report]. PMID- 27666716 TI - [A summary report from 29th Barany Society Meeting 2016]. PMID- 27666717 TI - [Research progress of mutational spectrum and pathophysiology of WFS1 gene in Wolfram syndrome and nonsyndromic low frequency sensorineural hearing loss]. AB - Compound homozygous or heterozygous mutations in WFS1 can lead to autosomal recessive Wolfram syndrome (WS), and heterozygous mutations in WFS1 can lead to autosomal dominant non-syndromic low frequency sensorineural hearing loss (LFSNHL). In addition, mutations in the WFS region has relationship with diabetes and psychiatric diseases. In this paper, we provide an overview of genetic research with different phenotypes, including WS and LFSNHL. PMID- 27666718 TI - [Advances of the treatments for thyroid carcinoma patients with laryngotracheal invasion]. AB - Thyroid carcinoma is one of the most common cancer in the head and neck and its incidence shows an increasing tendency. Due to the special anatomical location of thyroid carcinoma, patients will have a bad prognosis outcome when cancer invades larynx and trachea. Surgical treatment is still a preferred therapy for thyroid carcinoma with laryngotracheal invasion, because it has the advantages such as high survival rate, low recurrence rate, relieving of airway obstruction, improving of postoperative quality of life. Other therapies including radiotherapy, chemotherapy, 131I and molecular targeted therapy can also be used for treatments of thyroid carcinoma. This article reviews the current treatments for thyroid carcinoma with laryngotracheal invasion. PMID- 27666720 TI - Improvement of Gas-Sensing Performance of Large-Area Tungsten Disulfide Nanosheets by Surface Functionalization. AB - Semiconducting two-dimensional (2D) transition metal dichalcogenides (TMDCs) are promising gas-sensing materials due to their large surface-to-volume ratio. However, their poor gas-sensing performance resulting from the low response, incomplete recovery, and insufficient selectivity hinders the realization of high performance 2D TMDC gas sensors. Here, we demonstrate the improvement of gas sensing performance of large-area tungsten disulfide (WS2) nanosheets through surface functionalization using Ag nanowires (NWs). Large-area WS2 nanosheets were synthesized through atomic layer deposition of WO3 followed by sulfurization. The pristine WS2 gas sensors exhibited a significant response to acetone and NO2 but an incomplete recovery in the case of NO2 sensing. After AgNW functionalization, the WS2 gas sensor showed dramatically improved response (667%) and recovery upon NO2 exposure. Our results establish that the proposed method is a promising strategy to improve 2D TMDC gas sensors. PMID- 27666721 TI - Investigational histone deacetylase inhibitors for treating pancreatic adenocarcinoma. PMID- 27666722 TI - Greater occipital nerve block in the treatment of triptan-overuse headache: A randomized comparative study. AB - OBJECTIVES: This study aims to investigate the efficiency of a single and repeated greater occipital nerve (GON) block using lidocaine in the treatment of triptan-overuse headache (TOH), whose importance has increased lately. MATERIALS AND METHODS: In the study, 105 consecutive subjects diagnosed with TOH were evaluated. The subjects were randomized into three groups. In Group 1 (n=35), only triptan was abruptly withdrawn. In Group 2 (n=35), triptan was abruptly withdrawn and single GON block was performed. In Group 3 (n=35), triptan was abruptly withdrawn and three-stage GON block was performed. All patients were injected bilaterally with a total amount of 5 cc 1% lidocaine in each stage. During follow-up, the number of headache days per month, the severity of pain (VAS), the number of triptans used, and hsCRP and IL-6 levels were recorded three times; in the pretreatment period, in the second month post-treatment, and in the fourth month post-treatment. They were then compared. RESULTS: There was a statistically significant difference in the post-treatment fourth month in comparison with the pretreatment period in Group 3 (P<.05). Compared to Group 1, the number of headache days, VAS, and decrease in triptan need in Group 3 was statistically significant compared to Group 2 (P<.05). Compared to pretreatment, in the fourth month post-treatment, both hsCRP and IL-6 levels were lower only in Group 3 (P<.05). CONCLUSIONS: We are of the opinion that repeated GON block in addition to the discontinuation of medication has significant efficacy for TOH cases. PMID- 27666724 TI - Titanium Oxide/Silicon Moth-Eye Structures with Antireflection, p-n Heterojunctions, and Superhydrophilicity. AB - By employing KOH etching of silicon and hydrothermal growth of titanium oxide (TiO2), TiO2 nanorods assembled on the silicon micropyramids to form biomimetic composite coating, similar to moth-eye structures. The biomimetic composite coating possessed not only the micro-nano hierarchical structures but also the p n heterojunctions, resulting in a decrease in the reflection of incident light and an increase in the separation efficiency of photogenerated carriers. Meanwhile, the structures showed excellent superhydrophilicity, making for the self-cleaning of the material surface. We further demonstrate that by exploiting the advantages of this method, the application of such structures in the photocatalysis field is thus straightforward. PMID- 27666723 TI - Use of NRP1, a novel biomarker, along with VEGF-C, VEGFR-3, CCR7 and SEMA3E, to predict lymph node metastasis in squamous cell carcinoma of the tongue. AB - Lymph node (LN) metastasis has been suggested as a major prognostic factor for oral cancer. Knockdown of the growth factors and receptors involved in these metastatic mechanisms could significantly reduce LN metastasis and improve the survival of oral cancer patients after treatment. The present study, therefore, aimed to evaluate the expression levels of the following growth factors and receptors in squamous cell carcinoma (SCC) of the tongue: the vascular endothelial growth factor (VEGF)-C and VEGF-D, which bind to the cell surface tyrosine kinase receptor VEGF receptor-3 (VEGFR-3); C-C motif chemokine receptor 7 (CCR7); neuropilin (NRP)1 and NRP2; and semaphorin 3E (SEMA3E). Furthermore, we assessed microvessel density (MVD) and lymphatic vessel density (LVD) to demonstrate the correlation between these factors and regional LN metastasis, with respect to the clinicopathological features. Finally, we analyzed the correlation between these proteins and overall or disease-free survival, in order to demonstrate their prognostic value. Univariate analysis revealed a significant association between LN metastasis and the expression levels of VEGF-C, VEGFR-3, CCR7, NRP1, and SEMA3E, as well as LVD, in SCC cells. In contrast, multivariate analysis identified associations between LN metastasis and NRP1 expression, as well as between LN metastasis and LVD; however, no correlation was found between LN metastasis and the expression levels of the other proteins. The expression levels of VEGF-C, VEGFR-3, NRP1, and SEMA3E, as well as LVD, were correlated with disease-free survival time. These results indicate that LN metastasis is associated with poor survival in SCC. This study suggests that NRP1 expression and LVD are independent factors that are likely to predict the risk of LN metastasis in SCC of the tongue, whereas the expression of VEGF-C, VEGFR-3, CCR7, and SEMA3E are non-independent predictive factors. PMID- 27666719 TI - Cardiovascular disease and type 2 diabetes in evolutionary perspective: a critical role for helminths? AB - Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways. As part of a strategy to insure their own survival and reproduction, helminths exert multiple cardio protective effects on their host through their effects on immune function and blood lipid metabolism. Helminths consume blood lipids and glucose, alter lipid metabolism, and modulate immune function towards Th-2 polarization - which combined can lower blood cholesterol, reduce obesity, increase insulin sensitivity, decrease atheroma progression, and reduce likelihood of atherosclerotic plaque rupture. Traditional cardiometabolic risk factors, coupled with the mismatch between our evolved immune systems and modern, hygienic environments may interact in complex ways. In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease. PMID- 27666725 TI - Absence of collagen IX accelerates hypertrophic differentiation in the embryonic mouse spine through a disturbance of the Ihh-PTHrP feedback loop. AB - Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX alpha2- and alpha3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX -/- mice. Histological staining was used to show tissue morphology at different time points. Localization of extracellular matrix proteins as well as components of signaling pathways were analyzed by immunohistochemistry. Developing vertebral bodies of Col IX -/- mice were smaller and already appeared more compact at E12.5. At E15.5, vertebral bodies of Col IX /- mice revealed an increased number of hypertrophic chondrocytes as well as enhanced staining for the terminal differentiation markers alkaline phosphatase and collagen X. This correlates with an imbalance in the Ihh-PTHrP signaling pathway at this time point, reflected by an increase of Ihh and a concomitant decrease of PTHrP expression. An accelerated hypertrophic differentiation caused by a disturbed Ihh-PTHrP signaling pathway may lead to a higher bone mineral density in the vertebral bodies of newborn Col IX -/- mice and, as a result, to the early onset of disc degeneration. PMID- 27666727 TI - Biomedical Enhancement and Social Development: A Conservative Techno-Fix. AB - Allen Buchanan has argued for a linking of the ethics of human enhancement to the ethics of development more generally. The promise of the 'enhancement enterprise' is that it may help develop society, just as other technological advances have in the past. He proposes a framework of intellectual property rights, government action to ensure the poor can access the enhancements, an international organization to administer the diffusion of new enhancement technologies from the West to poor countries, and the diffusion within countries to the poorer populations. I take seriously his proposal of discussing biomedical enhancement in terms of the ethics of development. On these grounds of assessment, I argue that his proposal is politically conservative. To make the case, I distinguish conservatism in ethics from conservatism in politics; and I contextualize the proposal against the background of development economics and the neoliberal approach to development. PMID- 27666726 TI - Rab5a-mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells. AB - Rab5a, a key member of the Rab family of GTPases, was determined to be a regulator of vascular smooth muscle cell (VSMC) proliferation and migration. However, the exact regulatory mechanism remains unclear. As Rab5a has been shown to be associated with autophagy, which is essential for the conversion of VSMCs from a contractile to a synthetic phenotype in order to prevent cell death due to oxidative stress. The present study hypothesized that autophagy may be responsible for the proliferation and migration of VSMCs via the Rab5a protein. The aim of the present study was to evaluate the effect of Rab5a on autophagy in VSMCs. The human aorta vascular smooth muscle cell line, T/G HA-VSMCs, was treated with small interfering (si)RNA against Rab5a and/or platelet-derived growth factor (PDGF). Following treatment, the phenotype transition of the VSMCs was evaluated by detecting the mRNA and protien expression levels of VSMC molecular markers using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. In addition, autophagy in VSMCs was evaluated by western blotting for autophagy-associated proteins, flow cytometry of acidic vesicular organelles, punctate fluorescence of microtubule associated protein light chain 3 and transmission electron microscopy of typical scattered double-membrane vacuolar structures. Additionally, the proliferation, migration, cell cycle and apoptotic response of VSMCs were detected by sulforhodamine B assay, transwell assay and flow cytometry, respectively. The results revealed that transfection with siRNA against Rab5a led to a significant decrease in Rab5a protein expression, while the reduced expression trend of Rab5a was rescued by intervention with PDGF. Furthermore, cells transfected with siRNA against Rab5a inhibited the autophagy of VSMCs. Downregulated Rab5a inhibited the phenotype transition of VSMCs. Additionally, downregulated Rab5a led to slowed cell growth, decreased numbers of migrated cells, decreased numbers of cells at the G0-G1 phase and a higher apoptosis rate. However, PDGF significantly rescued these phenomena caused by siRNA against Rab5a. These results indicated that Rab5a mediated autophagy may regulate the phenotype transition and cell behavior of VSMCs through the activation of the extracellular-regulated kinase 1/2 signaling pathway. PMID- 27666728 TI - Cre-inducible site-specific recombination in zebrafish oligodendrocytes. AB - BACKGROUND: The conditional Cre/lox system has recently emerged as a valuable tool for studies on both embryonic and adult Zebrafish. Temporal control and site specific recombination are achieved by using the ligand-inducible CreERT2 and administration of the drug tamoxifen (TAM) or its active metabolite, 4 Hydroxytamoxifen (4-OHT). RESULTS: Here we report the generation of a transgenic Zebrafish line, which expresses an mCherry-tagged variant of CreERT2 under the control of the myelin basic protein a (mbpa) promoter. Our analysis shows that larval and adult expression of the transgene recapitulates the endogenous mbpa expression pattern in oligodendrocytes. Furthermore, combination with a Cre dependent EGFP reporter results in EGFP-expressing oligodendrocytes in the spinal cord, brain, and optic nerve in TAM- or 4-OHT-treated larvae and 4-month-old fish, but not in untreated controls. CONCLUSIONS: The transgenic Zebrafish line Tg(mbpa:mCherry-T2A-CreERT2 ) elicits CreERT2 expression specifically in myelinating glia cells. Cre-inducible targeted recombination of genes in oligodendrocytes will be useful to elucidate cellular and molecular mechanisms of myelination in vivo during development (myelination) and regeneration (remyelination) after injury to the central nervous system (CNS). It will also allow targeted expression and overexpression of genes of interest (transgenes) in oligodendrocytes at defined developmental and adult stages. Developmental Dynamics 246:41-49, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27666729 TI - Optimizing Microplate Biofilm Assays to Screen Anti-infective Surfaces. PMID- 27666730 TI - Bioelectrochemical Power-to-Gas: State of the Art and Future Perspectives. AB - Bioelectrochemical power-to-gas (BEP2G) is considered a potentially convenient way of storing renewable surplus electricity in the form of methane. In methane producing bioelectrochemical systems (BESs), carbon dioxide and electrical energy are converted into methane, using electrodes that supply either electrons or hydrogen to methanogenic archaea. This review summarizes the performance of methane-producing BESs in relation to cathode potential, electrode materials, operational strategies, and inoculum. Analysis and estimation of energy input and production rates show that BEP2G may become an attractive alternative for thermochemical methanation, and biochemical methanogenesis. To determine if BEP2G can become a future power-to-gas technology, challenges relating to cathodic energy losses, choice of a suitable electron donor, efficient reactor design/operation, and experience with large reactors need to be overcome. PMID- 27666731 TI - Enantioselective Pd-Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2 a]indolone Substrates: Efficient Syntheses of (-)-Goniomitine, (+) Aspidospermidine, and (-)-Quebrachamine. AB - The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (-)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (-)-quebrachamine, are reported herein. PMID- 27666732 TI - Review of emerging contaminants in aquatic biota from Latin America: 2002-2016. AB - Although it is known that emerging contaminants are widespread all over the globe, there is a gap of information about their distribution in some geographical areas, such as Latin America. The present bibliographic work reviews the available literature about the presence of organic emerging contaminants in Latin American freshwater and marine biota between 2002 and 2016 and includes 23 works from Argentina, Brazil, Chile, Colombia, Mexico, and Nicaragua. In particular, the present review provides an overview of the occurrence of continuously present contaminants such as pharmaceuticals, personal care products, and pyrethroid insecticides, as well as the new groups of persistent organic pollutants, the halogenated flame retardants and the perfluoroalkyl substances. A wide overview is provided, considering not only occurrence data but also effects and potential transfer through the food chain. Environ Toxicol Chem 2017;36:1716-1727. (c) 2016 SETAC. PMID- 27666733 TI - Analysis of a founder mutation in the TH gene in a cohort of greek patients with Parkinson's disease. PMID- 27666735 TI - A large cohort study confirming that specific haplotype 4A161PAS is exclusively associated with the Chinese FSHD1. PMID- 27666734 TI - Use of 3D models of congenital heart disease as an education tool for cardiac nurses. AB - BACKGROUND: Nurse education and training are key to providing congenital heart disease (CHD) patients with consistent high standards of care as well as enabling career progression. One approach for improving educational experience is the use of 3D patient-specific models. OBJECTIVES: To gather pilot data to assess the feasibility of using 3D models of CHD during a training course for cardiac nurses; to evaluate the potential of 3D models in this context, from the nurses' perspective; and to identify possible improvements to optimise their use for teaching. DESIGN: A cross-sectional survey. SETTING: A national training week for cardiac nurses. PARTICIPANTS: One hundred cardiac nurses (of which 65 pediatric and 35 adult). METHODS: Nurses were shown nine CHD models within the context of a specialized course, following a lecture on the process of making the models themselves, starting from medical imaging. Participants were asked about their general learning experience, if models were more/less informative than diagrams/drawings and lesion-specific/generic models, and their overall reaction to the models. Possible differences between adult and pediatric nurses were investigated. Written feedback was subjected to content analysis and quantitative data were analyzed using nonparametric statistics. RESULTS: Generally models were well liked and nurses considered them more informative than diagrams. Nurses found that 3D models helped in the appreciation of overall anatomy (86%), spatial orientation (70%), and anatomical complexity after treatment (66%). There was no statistically significant difference between adult and pediatric nurses' responses. Thematic analysis highlighted the need for further explanation, use of labels and use of colors to highlight the lesion of interest amongst improvements for optimizing 3D models for teaching/training purposes. CONCLUSION: 3D patient specific models are useful tools for training adult and pediatric cardiac nurses and are particularly helpful for understanding CHD anatomy after repair. PMID- 27666736 TI - Antibiotics and iron-limiting conditions and their effect on the production and composition of outer membrane vesicles secreted from clinical isolates of extraintestinal pathogenic E. coli. AB - PURPOSE: The focus of this study was to characterize the effect of clinically relevant stress-inducing conditions on the production and composition of proinflammatory outer membrane vesicles (OMVs) produced from ST131 extraintestinal pathogenic Escherichia coli (ExPEC) clinical isolates. EXPERIMENTAL DESIGN: A label-free method (relative normalized spectral index quantification, SINQ) was used to identify changes in the respective OMV proteomes following exposure of the ExPEC strains to antibiotics and low iron. Nanoparticle tracking analysis was used to quantify changes in abundance and size of OMVs produced by the gentamicin-resistant (GenR) and gentamicin-sensitive (GenS) ExPEC strains. RESULTS: Up to a 13.1-fold increase in abundance of particles were detected when the gentamicin-sensitive strain was exposed to a range of gentamicin concentrations. In contrast, no increase was observed for the gentamicin-resistant strain. Iron-limiting conditions had minimal effect on OMV production for either strain. Marked changes in the OMV proteome were observed for both strains including increases in Hsp100/Clp proteins, ATP-dependent ClpP protease, and regulatory proteins. CONCLUSION: These data provide information on changes in the composition of OMV particles derived from ExPEC strains generated in response to clinically relevant conditions. We show that the levels of the proinflammatory OMVs increase for gentamicin-sensitive ExPEC exposed to the antibiotic. PMID- 27666737 TI - Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years. AB - We analysed the association of independent variables with non-verbal cognition at 6 years in children with complete data (3441 from a cohort of 9901), of whom 415 were anaesthetised before the age of 5 years. Using multivariable regression, cognition was reduced by a mean (95% CI) score for children: anaesthetised before the age of 5 years, 2.1 (0.7-3.5), p = 0.004; born prematurely, 9.8 (4.1-15.4), p = 0.001; whose mothers smoked while pregnant, 2.3 (0.8-3.8), p = 0.004; whose mothers had lower IQ scores, 0.3 (0.2-0.3) for each unit reduction in maternal IQ, p < 0.0001. The association of child IQ with exposure to anaesthetic drugs was sensitive to missing data. PMID- 27666738 TI - Comparing a stratified treatment strategy with the standard treatment in randomized clinical trials. AB - The increasing emergence of predictive markers for different treatments in the same patient population allows us to define stratified treatment strategies. We consider randomized clinical trials that compare a standard treatment with a new stratified treatment strategy that divides the study population into subgroups receiving different treatments. Because the new strategy may not be beneficial in all subgroups, we consider in this paper an intermediate approach that establishes a treatment effect in a subset of patients built by joining several subgroups. The approach is based on the simple idea of selecting the subset with minimal p-value when testing the subset-specific treatment effects. We present a framework to compare this approach with other approaches to select subsets by introducing three performance measures. The results of a comprehensive simulation study are presented, and the relative merits of the various approaches are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27666739 TI - Response of lactating dairy cows to degree of steam-flaked barley grain in low forage diets. AB - This study was conducted to investigate the effects of processing method (grinding vs. steam flaking) and increasing densities of steam-flaked barley grain on dry matter intake (DMI), rumen pH and fermentation characteristics, digestibility of dry matter in the total digestive tract (DDTT), and milk production of dairy cows. Eight multiparous mid-lactation Holstein cows averaging 103 +/- 24 DIM, 44.5 +/- 4.7 kg milk/day and weighing 611 +/- 43 kg at the start of the experiment were used in a replicated 4 * 4 Latin square design with 21-day periods. Cows were fed diets consisting of (DM basis) 23.8% corn silage, 13.5% chopped alfalfa hay and 62.7% concentrate. The dietary treatments were either ground barley (GB) using a hammer mill or steam-flaked barley (SFB) - varying density at 390, 340 or 290 g/l. Processing method (GB vs. SFB) did not affect DMI (23.6 kg/day on average), DDTT (71.0% on average), milk yield (43.4 kg/day on average), milk components, rumen pH and molar proportions of acetate, propionate, butyrate and sorting activity. Ruminal isovalerate concentration tended (p = 0.06) to be higher for cows fed GB than those fed SFB-based diets. Decreasing the density of SFB from 390, 340 to 290 g/l tended to linearly increase DMI (p = 0.09), decrease total solids percentage of milk (p = 0.10) and linearly decreased milk urea nitrogen (12.8, 12.4 and 12.1 mg/dl; p = 0.04); also, the sorting index (SI) of the particles retained on the 19.0-mm sieve without affecting the SI of the particles retained on 8.0-mm, 1.18-mm or passed through 1.18-mm sieve (p = 0.05). These results indicated the limited effects of processing method (grinding vs. steam flaking) and densities of SFB (390, 290 or 290 g/l) on cows' performance and feed utilization for dairy cows fed low-forage diets. Therefore, both processing methods could be recommended under current feeding conditions of dairy cows. PMID- 27666740 TI - Evaluating IPMN and pancreatic carcinoma utilizing quantitative histopathology. AB - Intraductal papillary mucinous neoplasms (IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis (CP), IPMN, or pancreatic carcinoma (PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 +/- 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 +/- 0.16 for correctly classified lesions and 0.47 +/- 0.10 for incorrectly classified lesions (P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis. PMID- 27666741 TI - Early ototoxic changes in patients with germ cell tumor after first cycle of cisplatin-based therapy. AB - OBJECTIVE: To prospectively examine early hearing damage detectable with distortion product otoacoustic emission (DPOAE) after the first cycle of cisplatin treatment of patients with testicular tumor. STUDY DESIGN: Both ears of 137 consecutive patients were examined at 0.75 to 8 kHz before (B) and after (A) the first cycle of cisplatin (dose: 100 mg/m2 / 5 days). METHODS: The mean amplitudes (B vs. A) were compared with paired t test at each frequency. Ototoxic changes were considered when an individual amplitude difference (B-A) > 14 dB at 0.75 Hz or > 7 db at 1 to 8 kHz occurred. RESULTS: The mean amplitudes were statistically significantly lower after first cycle at 0.75, 6, and 8 kHz. The majority of patients (96%) presented positive differences (B-A) in one or both ears; in 85 (62%) cases, the positive difference reached the level of ototoxicity out of which 34 (40%) and 19 (22%) of patients suffered ototoxicity in one or both ears, respectively. The difference between right and left ears in distribution of ototoxic cases was nonsignificant. Forty-five (33%) and four (3%) patients showed ototoxicity at two or more frequencies in one or both ears, respectively. An increased proportion of ototoxic cases can be seen at 0.75 to 1 kHz and 6 to 8 kHz. CONCLUSION: After the first cycle of cisplatin treatment, early ototoxicity occurs in close to two-thirds of patients, as identified by measuring DPOAE. Therefore, further research for biomarkers is required, which can predict patients at risk in order to avoid an irreversible hearing loss by personalized, preventive therapies. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1909 1915, 2017. PMID- 27666742 TI - Editorial commentary: Biomarkers in heart failure, between scientific scrutiny and exploration. PMID- 27666743 TI - Phycicoccus ginsengisoli sp. nov., isolated from cultivated ginseng soil. AB - Ginseng-cultivated soil is an excellent habitat for soil-borne bacteria to proliferate. A novel strain, DCY87T, was isolated from ginseng-cultivated soil in Gochang County, Republic of Korea, and subsequently characterized by polyphasic approach. Cells were rod shaped, non-motile, aerobic, Gram-reaction-positive, oxidase-negative and catalase-positive. 16S rRNA gene sequence analysis showed that strain DCY87T shared the highest similarity to 'Phycicoccus ochangensis' L1b b9 (98.7 %). Closely phylogenetic relatives of strain DCY87T were identified: Phycicoccus ginsenosidimutans BXN5-13T (97.9 %), Phycicoccus soli THG-a14T (97.8 %), Phycicoccus bigeumensis MSL-03T (97.3 %), Phycicoccus cremeus V2M29T (97.3 %), Phycicoccus aerophilus 5516T-20T (97.3 %), Phycicoccus dokdonensis DS-8T (97.3 %) and Phycicoccus jejuensis KSW2-15T (97.1 %). The major polar lipids were classified as phosphatidylinositol and diphosphatidylglycerol. The major cellular fatty acids were composed of iso-C15 : 0, anteiso-C15:0, C17 : 0 and C17 : 1omega8c. The menaquinone was resolved as MK-8(H4). Strain DCY87T contained meso diaminopimelic acid as diamino acid in the cell-wall peptidoglycan and glucose, xylose and rhamnose in the whole-cell sugar. The genomic DNA G+C content was calculated to be 72.7 mol%. DNA-DNA hybridization value between strain DCY87T and 'P. ochangensis' L1b-b9 was estimated to be 50 %. However, DNA-DNA hybridization value obtained between strain DCY87T and P. ginsenosidimutans BXN5-13T, P. soli THG-a14T and P. bigeumensis MSL-03T was well below 17 %. In general, polyphasic taxonomy demonstrated that DCY87T strain represented a novel species within the genus Phycicoccus. Accordingly, we propose the name Phycicoccus ginsengisoli sp. nov. The type strain is DCY87T (=KCTC 39635T=JCM 31016T). PMID- 27666744 TI - Associations between social vulnerabilities and dietary patterns in European children: the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study. AB - Socio-economic inequalities in childhood can determine dietary patterns, and therefore future health. This study aimed to explore associations between social vulnerabilities and dietary patterns assessed at two time points, and to investigate the association between accumulation of vulnerabilities and dietary patterns. A total of 9301 children aged 2-9 years participated at baseline and 2 year follow-up examinations of the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS study. In all, three dietary patterns were identified at baseline and follow-up by applying the K means clustering algorithm based on a higher frequency of consumption of snacks and fast food (processed), sweet foods and drinks (sweet), and fruits and vegetables (healthy). Vulnerable groups were defined at baseline as follows: children whose parents lacked a social network, children from single-parent families, children of migrant origin and children with unemployed parents. Multinomial mixed models were used to assess the associations between social vulnerabilities and children's dietary patterns at baseline and follow-up. Children whose parents lacked a social network (OR 1.31; 99 % CI 1.01, 1.70) and migrants (OR 1.45; 99 % CI 1.15, 1.83) were more likely to be in the processed cluster at baseline and follow-up. Children whose parents were homemakers (OR 0.74; 99 % CI 0.60, 0.92) were less likely to be in the processed cluster at baseline. A higher number of vulnerabilities was associated with a higher probability of children being in the processed cluster (OR 1.78; 99 % CI 1.21, 2.62). Therefore, special attention should be paid to children of vulnerable groups as they present unhealthier dietary patterns. PMID- 27666745 TI - Molecular Pathway of Microtubule Organization at the Golgi Apparatus. AB - The Golgi apparatus controls the formation of non-centrosomal microtubule arrays important for Golgi organization, polarized transport, cell motility, and cell differentiation. Here, we show that CAMSAP2 stabilizes and attaches microtubule minus ends to the Golgi through a complex of AKAP450 and myomegalin. CLASPs stabilize CAMSAP2-decorated microtubules but are not required for their Golgi tethering. AKAP450 is also essential for Golgi microtubule nucleation, and myomegalin and CDK5RAP2 but not CAMSAP2 contribute to this function. In the absence of centrosomes, AKAP450- and CAMSAP2-dependent pathways of microtubule minus-end organization become dominant, and the presence of at least one of them is needed to maintain microtubule density. Strikingly, a compact Golgi can be assembled in the absence of both centrosomal and Golgi microtubules. However, CAMSAP2- and AKAP450-dependent Golgi microtubules facilitate Golgi reorientation and cell invasion in a 3D matrix. We propose that Golgi-anchored microtubules are important for polarized cell movement but not for coalescence of Golgi membranes. PMID- 27666746 TI - Control of Oriented Tissue Growth through Repression of Organ Boundary Genes Promotes Stem Morphogenesis. AB - The origin of the stem is a major but poorly understood aspect of plant development, partly because the stem initiates in a relatively inaccessible region of the shoot apical meristem called the rib zone (RZ). We developed quantitative 3D image analysis and clonal analysis tools, which revealed that the Arabidopsis homeodomain protein REPLUMLESS (RPL) establishes distinct patterns of oriented cell division and growth in the central and peripheral regions of the RZ. A genome-wide screen for target genes connected RPL directly to many of the key shoot development pathways, including the development of organ boundaries; accordingly, mutation of the organ boundary gene LIGHT-SENSITIVE HYPOCOTYL 4 restored RZ function and stem growth in the rpl mutant. Our work opens the way to study a developmental process of importance to crop improvement and highlights how apparently simple changes in 3D organ growth can reflect more complex internal changes in oriented cell activities. PMID- 27666748 TI - A laboratory practical illustrating the use of the ChIP-qPCR method in a robust model: Estrogen receptor alpha immunoprecipitation using Mcf-7 culture cells. AB - Chromatin immunoprecipitation followed by qPCR analysis (ChIP-qPCR) is a widely used technique to study gene expression. A large number of students in molecular biology and more generally in life sciences will be confronted with the use of this technique, which is quite difficult to set up and can lead to misinterpretation if not carefully managed. This article describes a four-session laboratory practical designed for Masters students to introduce this technique. During the practical, students work in pairs. They extract chromatin from MCF-7 culture cells stimulated or not by estrogens, then immunoprecipitate the transcription factor estrogen receptor alpha using an antibody directed against it. Students then measure the enrichment of promoter DNA target sequences from the chromatin that coprecipitates by qPCR. These are two estrogen responsive genes, pS2 (trefoil factor one) and PGR (the progesterone receptor). They learn how to analyze their ChIP-qPCR data by two methods: percent input and fold enrichment, and are taught about the interpretation limits of these two calculation methods. Thus, this practical is a good framework for an in-depth discussion of how this technique can be used to study gene expression and for raising awareness of the importance of careful interpretation of results. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):152 160, 2017. PMID- 27666747 TI - Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma. AB - Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2 T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. PMID- 27666749 TI - Discovery of a Superconducting Cu-Bi Intermetallic Compound by High-Pressure Synthesis. AB - A new intermetallic compound, the first to be structurally identified in the Cu Bi binary system, is reported. This compound is accessed by high-pressure reaction of the elements. Its detailed characterization, physical property measurements, and ab initio calculations are described. The commensurate crystal structure of Cu11 Bi7 is a unique variation of the NiAs structure type. Temperature-dependent electrical resistivity and heat capacity measurements reveal a bulk superconducting transition at Tc =1.36 K. Density functional theory calculations further demonstrate that Cu11 Bi7 can be stabilized (relative to decomposition into the elements) at high pressure and temperature. These results highlight the ability of high-pressure syntheses to allow for inroads into heretofore-undiscovered intermetallic systems for which no thermodynamically stable binaries are known. PMID- 27666750 TI - A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects. AB - : Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. SUMMARY: Background Prothrombin fragment 1 + 2 (F1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F1 + 2 , TAT and D-dimer in a non bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. PMID- 27666751 TI - In vivo cloning of large chromosomal segments into a BAC derivative by generalized transduction and recombineering in Salmonella enterica. AB - Recombineering has been used to facilitate the development of in vivo cloning methods. However, the method relies heavily on PCR, which still generates a much higher error rate than DNA replication in vivo, even when amplifying large DNA inserts. Here, a precise technique is reported in Salmonella enterica that enables the cloning of up to at least 19 kb target chromosomal DNA segments that had been marked by FRTs, which were derived from two consecutive lambda Red mediated recombination events. P22 phage was utilized to transduce the target DNA segments from donor strains to recipient strains harboring a derivative of bacterial artificial chromosome (BAC) containing a FRT and a plasmid expressing Flp recombinase. This method was successful in cloning a gene cluster responsible for lipopolysaccharide (LPS) modifications that confer polymyxin B resistance and in complementing its mutant. Further optimized procedures should be widely applicable because large insert fragments are precise clones of the wild-type genome. PMID- 27666752 TI - Giant left anterior descending artery aneurysm resulting in sudden death. AB - Coronary artery aneurysm is a rare congenital or vascular inflammation-based anomaly for which the clinical course and optimal timing of treatment remain unclear. Here, we report a case of sudden death caused by a giant coronary artery aneurysm of the left anterior descending artery that presented with chest pain. This case suggests that urgent interventional or surgical repair is needed when a large coronary aneurysm presents with acute ischemic symptoms. PMID- 27666753 TI - Anticoagulation management in non-valvular atrial fibrillation in rural and remote Crete. A single-center study from the region of Sitia. PMID- 27666754 TI - Obstetrical transfusion medicine knowledge among faculty and trainee obstetricians: a prospective knowledge assessment study. AB - OBJECTIVES: To evaluate the current state of transfusion medicine (TM) knowledge among obstetricians using a valid assessment tool. BACKGROUND: Transfusion issues are common in obstetrical patients. METHODS: Knowledge topics were identified and rated by experts in obstetrics, anaesthesia, haematology and TM using a modified Delphi method. A knowledge assessment tool was developed and validated during pilot testing. The assessment tool, consisting of 15 multiple choice questions, was administered electronically to members of the Society of Obstetricians and Gynaecologists of Canada (SOGC). RESULTS: A total of 192 SOGC members completed the assessment tool: 121 faculty obstetricians and 71 trainees. The average score was 65.8% +/- 15.5. Scores for faculty were higher than trainees (68.9% +/- 13.5 vs 60.6% +/- 17.2; P < 0.001). Respondents performed well on questions related to red blood cell (RBC) transfusion and anaemia management but had lower scores on questions related to non-RBC transfusion and management of alloantibodies and fetomaternal haemorrhage (FMH) testing. There was no improvement in scores with increasing trainee level, years of practice, hours of formal TM training or experience with massive haemorrhage. Only self-rated knowledge was associated with scores ['no knowledge' or 'beginner' 63.1% +/- 15 vs 'intermediate' or 'advanced' 68.9% +/- 13.3 (P = 0.007)]. Of the respondents, 93.8% felt additional training in TM would be helpful. CONCLUSIONS: Overall knowledge assessment scores indicate the need for educational intervention, particularly with respect to non RBC blood product use, management of FMH and management of pregnancies complicated by alloantibodies. The study also demonstrated a desire for additional TM training. PMID- 27666755 TI - An endogenous foreign body found after subconjunctival hemorrhage. PMID- 27666756 TI - Phenibut overdose. PMID- 27666757 TI - Diabetes Trend and Impact on Risk of Cardiovascular Disease in Middle-Aged Japanese People - The CIRCS Study. AB - BACKGROUND: The aim of this study was to examine whether the burden of diabetes on cardiovascular disease (CVD) in Japan has increased in recent years.Methods and Results:Three cohorts were established, consisting of Japanese residents aged 40-69 years, in 1992-1995 (n=8,744), 1996-1999 (n=7,996), and 2000-2003 (n=7,273). All participants had follow-up for a median of 10 years. Diabetes was defined according to the following criteria: (1) fasting serum glucose >=7.0 mmol/L; (2) non-fasting serum glucose >=11.1 mmol/L; or (3) anti-diabetic treatment at baseline. During follow-up, the number of CVD incidents was 277 in the first, 214 in the second, and 190 in the third cohorts. The prevalence of diabetes increased slightly over time. Adjusting for traditional cardiovascular risk factors, multivariable HR (95% CI) for diabetes as a cardiovascular risk factor were 1.40 (0.91-2.14) in the first, 1.93 (1.25-3.00) in the second, and 2.59 (1.77-3.81) in the third cohorts. The population attributable fraction of CVD due to diabetes was 2.8%, 5.6%, and 12.4%, respectively. CONCLUSIONS: This is the first study in middle-aged Japanese people to clarify an increased burden of CVD due to diabetes since the early 1990 s. Further efforts are needed to prevent and control diabetes through lifestyle modification and treatment. (Circ J 2016; 80: 2343-2348). PMID- 27666758 TI - Risk of end-stage renal disease in Japanese patients with chronic kidney disease increases proportionately to decline in estimated glomerular filtration rate. AB - Predominantly based on North American and European studies, 30% to 40% declines in estimated glomerular filtration rate (eGFR) over a few years are strongly associated with the risk of end-stage renal disease (ESRD) and have been proposed as surrogate endpoints of ESRD for clinical research. However, this association has not been systematically quantified in Asian populations. To do this we studied adult Japanese patients with baseline eGFR 10-59 ml/min/1.73m2. Changes in eGFR from baseline measured by centrally assessed serum creatinine were linked to subsequent ESRD in 2410 patients after one year and in 2079 patients after year 2. After year 1, 1.4% experienced a 53% decrease in eGFR (equivalent to doubling of serum creatinine), whereas 4.3% and 9.7% had eGFR decrease of 40% or 30% or more, respectively. The corresponding numbers after 2 years were 4.2%, 10.9%, and 19.3%, respectively. After year 1 baseline period, 498 patients developed ESRD over a median follow-up of 2.9 years (365 ESRD cases over a median follow-up of 2 years after year 2). In year 1, after accounting for potential confounders, a strong linear association was found between eGFR declines and subsequent ESRD, with adjusted hazard ratios of 20.7 (95% confidence interval 14.3-30.1) for a 53% decrease, 9.6 (7.4-12.5) for a 40% decrease, and 5.3 (4.1 6.9) for a 30% decrease compared to no change. Corresponding hazard ratios for year two analysis were 17.3 (11.8-25.3), 6.5 (4.7-9.1), and 3.1 (2.2-4.4), respectively. The associations were consistent across demographics and kidney diseases. Thus, 30% to 40% declines in eGFR are strongly associated with the risk of ESRD in Japanese patients with reduced eGFR, broadening global implications as a surrogate endpoint in clinical research. PMID- 27666760 TI - Optimization of total RNA isolation from human urinary sediment. AB - Extracting RNA from human urinary sediment is notoriously challenging because of cell paucity and hostile environment and column-based commercial kits using silica technology are commonly used. Nonetheless, in our experience, this methodology yields low amounts of total RNA and has low rates of success. We replaced the column-based commercial kit by a protocol using guanidine isothiocyanate-phenol-chloroform buffer (Trizol reagent) followed by addition of glycogen as a carrier and precipitation with isopropanol plus sodium acetate. This methodology was more affordable and efficient for urinary sediment total RNA isolation than silica technology, resulting in higher concentrations of total RNA of better quality. PMID- 27666759 TI - Ligand trap of the activin receptor type IIA inhibits osteoclast stimulation of bone remodeling in diabetic mice with chronic kidney disease. AB - Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr-/- high fat-fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 mice were given vehicle twice weekly from week 22 until the mice were killed at 28 weeks of age. The animals were then evaluated by skeletal histomorphometry, micro-computed tomography, mechanical strength testing, and ex vivo bone cell culture. Results in the CKD groups were compared with those of the 16 sham-operated ldlr-/- high fat-fed mice. Sham-operated mice had low-turnover osteodystrophy and skeletal frailty. CKD stimulated bone remodeling with significant increases in osteoclast and osteoblast numbers and bone resorption. Compared with mice with CKD and sham operated mice, RAP-011 treatment eliminated the CKD-induced increase in these histomorphometric parameters and increased trabecular bone fraction. RAP-011 significantly increased cortical bone area and thickness. Activin A-enhanced osteoclastogenesis was mediated through p-Smad2 association with c-fos and activation of nuclear factor of activated T cells c1 (NFATc1). Thus, an ActRIIA ligand trap reversed CKD-stimulated bone remodeling, likely through inhibition of activin-A induced osteoclastogenesis. PMID- 27666761 TI - A global multicenter study on reference values: 1. Assessment of methods for derivation and comparison of reference intervals. AB - OBJECTIVES: The IFCC Committee on Reference Intervals and Decision Limits coordinated a global multicenter study on reference values (RVs) to explore rational and harmonizable procedures for derivation of reference intervals (RIs) and investigate the feasibility of sharing RIs through evaluation of sources of variation of RVs on a global scale. METHODS: For the common protocol, rather lenient criteria for reference individuals were adopted to facilitate harmonized recruitment with planned use of the latent abnormal values exclusion (LAVE) method. As of July 2015, 12 countries had completed their study with total recruitment of 13,386 healthy adults. 25 analytes were measured chemically and 25 immunologically. A serum panel with assigned values was measured by all laboratories. RIs were derived by parametric and nonparametric methods. RESULTS: The effect of LAVE methods is prominent in analytes which reflect nutritional status, inflammation and muscular exertion, indicating that inappropriate results are frequent in any country. The validity of the parametric method was confirmed by the presence of analyte-specific distribution patterns and successful Gaussian transformation using the modified Box-Cox formula in all countries. After successful alignment of RVs based on the panel test results, nearly half the analytes showed variable degrees of between-country differences. This finding, however, requires confirmation after adjusting for BMI and other sources of variation. The results are reported in the second part of this paper. CONCLUSION: The collaborative study enabled us to evaluate rational methods for deriving RIs and comparing the RVs based on real-world datasets obtained in a harmonized manner. PMID- 27666762 TI - A global multicenter study on reference values: 2. Exploration of sources of variation across the countries. AB - OBJECTIVES: The intent of this study, based on a global multicenter study of reference values (RVs) for serum analytes was to explore biological sources of variation (SVs) of the RVs among 12 countries around the world. METHODS: As described in the first part of this paper, RVs of 50 major serum analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as the partial correlation coefficient (rp). RESULTS: Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related variations of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged fromthe rp, BMI related changes were observed for many nutritional and inflammatory markers in almost all countries. However, the slope of linear regression of BMI vs. RV differed greatly among countries for some analytes. Alcohol and smoking related changes were observed less conspicuously in a limited number of analytes. CONCLUSION: The features of sex, age, alcohol, and smoking-related changes in RVs of the analytes were largely comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases. PMID- 27666763 TI - MicroRNA-19a-3p enhances the proliferation and insulin secretion, while it inhibits the apoptosis of pancreatic beta cells via the inhibition of SOCS3. AB - MicroRNAs (miRNAs or miRs), a group of small non-coding RNAs, have been demonstrated to play key roles in various physicological processes and diseases, including diabetes, the most common metabolic disorder. However, the underlying mechanisms remains largely unknown. In this study, we aimed to investigate the role of miR-19a-3p in diabetes. The results of RT-qPCR demonstrated that the level of miR-19a-3p was significantly decreased in the diabetic patients, and that the decreased miR-50a-5p level was significantly associated with a high concentration of blood glucose. miR-19a-3p mimic was further used to transfect pancreatic beta cells, and we found that the overexpression of miR-19a-3p promoted cell proliferation and insulin secretion, while it suppressed the apoptosis of pancreatic beta cells. Suppressor of cytokine signaling 3 (SOCS3) was further identified as a direct target gene of miR-19a-3p, and its protein level was significantly decreased following the overexpression of miR-19a-3p. Moreover, the siRNA-induced downregulation of SOCS3 also enhanced cell proliferation and insulin secretion, while it inhibited the apoptosis of pancreatic beta cells. In addition, the overexpression of SOCS3 reversed the effects of miR-19a-3p overexpression on cell proliferation, insulin secretion and on the apoptosis of pancreatic beta cells, which further indicates that SOCS3 acts as a downstream effector in the miR-19a-3p-mediated function of pancreatic beta cells. Finally, the level of SOCS3 was increased in diabetic patients, and inversely correlated with the miR-19a-3p level, suggesting that the downregulation of miR-19a-3p leads to the upregulation of SOCS3, which contributes to the dysfunction of pancreatic beta cells. On the whole, the findings of this study suggest that miR-19a-3p plays an important role in beta cell function, and that the miR-19a-3p/SOCS3 axis may become a potential therapeutic target for diabetes. PMID- 27666765 TI - Clinical significance of BRAF V600E mutational status in capsular nevi of sentinel lymph nodes in patients with primary cutaneous melanoma. AB - Capsular nevi (CN) are clusters of benign melanocytes situated in the capsule of lymph nodes and occur in up to 20% of lympadenectomy specimens. The molecular profile of CN in relation to prognostic parameters in patients with primary cutaneous melanoma (PCM) has not been previously investigated. We assessed BRAF V600E mutation by immunohistochemistry (IHC) in the CN of sentinel lymph nodes (SLN) in PCM patients and correlated the findings with demographic characteristics, PCM histopathologic and molecular features, and clinical outcome parameters. Seventy-eight cases of CN involving SLN of PCM patients were evaluated for BRAF V600E mutation by IHC. The results were correlated with patient demographics, PCM histopathologic and molecular features, and outcome measures. Thirty-six (46%) of 78 CN cases expressed BRAF V600E mutation by IHC. Nineteen (53%) of those BRAF-positive CN cases were from patients with at least American Joint Committee on Cancer stage II melanoma, whereas 62% of BRAF negative CN cases (26/42) were from patients with stage I melanoma (P = .013). Twelve (33%) of the 36 BRAF-positive CN cases had metastatic melanoma involving lymph nodes, compared with 14% (6/42) of BRAF-negative CN cases (P = .061). CN mutation status was not associated with patient demographics, histopathologic or molecular features of the PCM, or survival outcomes. A high percentage of CN identified in the SLN of patients with PCM harbor BRAF V600E mutation. Positive mutation was associated with adverse clinicopathological parameters, specifically increased tumor stage and lymph node metastasis. These findings suggest that BRAF V600E mutation in CN of SLN may be useful as an adverse predictive biomarker in patients with melanoma. PMID- 27666764 TI - Low-grade Schwann cell neoplasms with leptomeningeal dissemination: clinicopathologic and autopsy findings. AB - Leptomeningeal dissemination of low-grade Schwann cell neoplasms is an exceptionally rare occurrence and has not been well documented in the literature. We encountered 2 cases of leptomeningeal dissemination of low-grade Schwann cell neoplasms. Patient 1 was a 63-year-old woman with neurofibromatosis type 1 and a progressive low-grade malignant peripheral nerve sheath tumor developing from a diffuse/plexiform orbital neurofibroma that arose in childhood. The neoplasm demonstrated local and leptomeningeal dissemination intracranially leading to the patient's death. There was partial loss of H3K27 tri-methylation, p16 and collagen IV. Patient 2 was a 60-year-old man without neurofibromatosis type 1 who presented with cranial nerve symptoms and a disseminated neoplasm with a Schwann cell phenotype. The neoplasm stabilized after irradiation and chemotherapy, but the patient died of medical complications. Autopsy findings documented disseminated leptomeningeal disease in the intracranial and spinal compartment. H3K27M tri-methylation was preserved. The clinicopathologic and autopsy findings are studied and presented, and the literature is reviewed. PMID- 27666766 TI - Immunohistochemical analysis of the novel marginal zone B-cell marker IRTA1 in malignant lymphoma. AB - Marginal zone lymphoma (MZL) is a low-grade B-cell lymphoma derived from marginal zone B cells. Because of a lack of specific immunohistochemical markers, MZL is mainly diagnosed based on the cytological appearance and growth pattern of the tumor. Marginal zone B cells were recently shown to selectively express immunoglobulin superfamily receptor translocation-associated 1 (IRTA1), but the antibody used in that study is not commercially available. We therefore investigated the IRTA1 expression in nonneoplastic lymphoid tissues and 261 malignant lymphomas, examining the ability of a commercially available antibody to accurately diagnose MZL. Among 37 MZLs, 23 of 25 extranodal MZLs of mucosa associated lymphoid tissue (MALT lymphomas), 3 of 6 splenic MZLs and 3 of 6 nodal MZLs were positive for IRTA1. Among the 98 diffuse large B-cell lymphomas, 33 were positive for IRTA1, including 1 of 38 follicular lymphomas, and all precursor B-lymphoblastic (2/2) and T-lymphoblastic (7/7) leukemia/lymphomas. Other mature B-cell and T-cell lymphomas, and Hodgkin lymphoma were negative for IRTA1. In MALT lymphoma, positive cells were detected mainly in intraepithelial and subepithelial marginal zone B cells. In 1 case of grade 3 follicular lymphoma, IRTA1 was also expressed in the area of large cell transformation. When tumors were classified as germinal center B cell-like (GCB) or non-GCB using the algorithm of Hans, positive expression of IRTA1 was correlated significantly with non-GCB diffuse large B-cell lymphomas (P < .05). These results demonstrated the ability of the commercially available IRTA1 antibody to distinguish MALT lymphoma from other low-grade B-cell lymphomas. PMID- 27666767 TI - Poorly cohesive cell (diffuse-infiltrative/signet ring cell) carcinomas of the gallbladder: clinicopathological analysis of 24 cases identified in 628 gallbladder carcinomas. PMID- 27666768 TI - Cytomegalovirus (CMV) in gastrointestinal mucosal biopsies: should a pathologist perform CMV immunohistochemistry if the clinician requests it? AB - Cytomegalovirus (CMV) causes clinically significant gastrointestinal (GI) injury. CMV inclusions can be identified on routine hematoxylin and eosin (H&E) stain, but immunohistochemistry (IHC) is also available for identifying CMV in tissue. The advent of accountable care organization models of care bring into question whether it is cost-effective for immunohistochemistry to be performed upfront at the request of clinicians and whether the quality of viral detection is compromised when the diagnosis of CMV is predicated on histologic review. In this study, a retrospective review of GI biopsies with CMV evaluations was performed. There were 449 cases with clinical requests to rule out CMV and 238 CMV analyses initiated by the pathologist without a clinical request. Among the cases that included a clinician's request, 37 had CMV detected. Immunostaining was performed on 26 cases, while a diagnosis based on readily identifiable viral inclusions on H&E-stained slides was made in 11. Among pathologist-initiated work-ups, 15 were CMV+, 3 of which had inclusions identified by H&E only. Among 38 CMV cases for which IHC had been performed, 27 had overt viral inclusions obvious on H&E. Seventy-two cases revealed uninflamed GI mucosa, and although a clinical concern about CMV infection was present, a CMV IHC work-up was not initially performed; all were negative for CMV by IHC and H&E. Clinical suspicion for CMV has a high yield for CMV detection, but "upfront" testing is likely unnecessary. Careful histopathologic review by a pathologist remains critical in the efficient and cost-effective detection of CMV. PMID- 27666769 TI - Mechanisms of DNA disentangling by type II topoisomerases: Comment on "Disentangling DNA molecules" by Alexander Vologodskii. PMID- 27666770 TI - Importance of disentanglement and entanglement during DNA replication and segregation: Comment on: "Disentangling DNA molecules" by Alexander Vologodskii. PMID- 27666771 TI - Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer. AB - Tissue microenvironment functions as a pivotal mediator in colorectal carcinogenesis, and its alteration can cause some important cellular responses including epigenetic events. The present study examined histologically altered tissue structure, DNA methyltransferases (DNMTs) and their corresponding expression of target microRNAs (miRNA). Tissues resected by surgery were from primary colorectal carcinoma. These samples were from three locations: and were >=10, 5 and <=2 cm away from the proximal lesion of colon cancer, and marked as no. 1, no. 2 and no. 3, respectively. Histological alteration was assessed by H&E staining, expression of DNMT1, DNMT3A, and DNMT3B was detected by immunohistochemistry and western blotting, microarray chip was used to screen distinguishable miRNAs and miRNAs targeting DNMTs whose validation assay was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Our results revealed that normal crypt structure was shown in no. 1, while many aberrant crypt foci appeared in no. 3. Significant upregulation of DNMT1, DNMT3A, and DNMT3B expression was found in para-carcinoma tissues, compared with the histopathologically unchanged tissues (P<0.05), furthermore, distinguishable expression profiling was observed of target miRNAs in tissues with different distance. Our results provide additional insights for future research of colorectal carcinogenesis by introducing the tissue microenvironment. PMID- 27666772 TI - Dysferlin mutations and mitochondrial dysfunction. AB - Dysferlinopathies are caused by mutations in the DYSF gene and patients may present with proximal or distal myopathy. Dysferlin is responsible for membrane resealing, and mutations may result in a defect in membrane repair following mechanical or chemical stress, causing an influx of Ca2+. Since mitochondria are involved in Ca2+ buffering, we hypothesised that mitochondrial defects may be present in skeletal muscle biopsies from patients with mutations in this gene. The aim was to characterise mitochondrial defects in muscle from patients with dysferlinopathies. Here, we analysed skeletal muscle biopsies for eight patients by quadruple immunofluorescent assay to assess oxidative phosphorylation protein abundance. Long-range PCR in single muscle fibres was used to look for presence of clonally expanded large-scale mitochondrial DNA rearrangements in patients' skeletal muscle (n = 3). Immunofluorescence demonstrated that the percentage of complex I- and complex IV-deficient fibres was higher in patients with DYSF mutations than in age-matched controls. No clonally expanded mtDNA deletions were detected using long-range PCR in any of the analysed muscle fibres. We conclude that complex I and complex IV deficiency is higher in patients than age matched controls but patients do not have rearrangements of the mtDNA. We hypothesise that respiratory chain deficiency may be the results of an increased cytosolic Ca2+ concentration (due to a membrane resealing defect) causing mitochondrial aberrations. PMID- 27666773 TI - Thomsen disease with ptosis and abnormal MR findings. AB - Myotonia congenita is a non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction caused by a mutation in the gene encoding skeletal muscle chloride channel-1 (CLCN1). We encountered a case of Thomsen disease with ptosis. A short tau inversion recovery MR imaging demonstrated high-intensity lesions in the levator palpebrae superioris muscles. Molecular genetic testing revealed a heterozygosity for the c.1439C>A (p.P480H) mutation in the CLCN1 gene. The expression level of ClC-1 was significantly reduced on the sarcolemma of the biceps brachii muscle from the patient, compared with that from healthy volunteer. Functional analysis of the p.P480H mutation is required for further elucidating the pathogenesis of Thomsen disease. PMID- 27666774 TI - The frequency of late-onset Pompe disease in pediatric patients with limb-girdle muscle weakness and nonspecific hyperCKemia: A multicenter study. AB - The aim of this multicenter study was to screen for late-onset Pompe disease in high-risk children with limb-girdle muscle weakness and nonspecific hyperCKemia using the dried blood spot (DBS) test. Seventy-two children from four pediatric neurology departments in Turkey were enrolled in the study: 37 with limb-girdle muscle weakness and 35 with nonspecific hyperCKemia. Acid alpha-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry. Six patients tested positively for Pompe disease. In three patients, one with the limb-girdle muscle weakness and two with nonspecific hyperCKemia, this was confirmed by genetic analysis. The overall frequency of late-onset Pompe disease in the study population was 4.2%. The c.1784C>T mutation found in one patient is a new mutation whereas the c.1655T>C mutation detected in the other two patients is not novel. In conclusion, Pompe disease should be suspected in patients with limb girdle muscle weakness and nonspecific hyperCKemia. The DBS test is a safe and reliable method of diagnosis but must be confirmed by genetic analysis. In patients with a positive DBS test and negative genetic analysis, tissue assay of GAA should be considered. PMID- 27666775 TI - Muscle MRI in Duchenne muscular dystrophy: Evidence of a distinctive pattern. AB - The purpose of this study was to describe the pattern of muscle involvement using MRI findings and correlate with functional as well as muscle strength measurements. Fifty genetically confirmed DMD children with a mean age of 7.6 +/- 2.8 (4-15 years) underwent muscle MRI and qualitative assessment was done for muscle changes using Mercuri staging for fibro-fatty replacement on T1 sequence and Borsato score for myoedema on STIR sequence. Detailed phenotypic characterisation was done with Manual muscle testing (modified MRC grading) and Muscular Dystrophy Functional Rating Scale (MDFRS). Mercuri scoring showed severe fibro-fatty changes in Gluteus medius, minimus and Adductor magnus followed by moderate to severe changes in Gluteus maximus and Quadriceps muscles. Total sparing of Gracilis, Sartorius and Semimembranosus muscles was observed. Superficial posterior and lateral leg muscles were preferentially involved with sparing of deep posterior and anterior leg muscles. Myoedema showed significant inverse correlation with fatty infiltration in thigh muscles. Similarly, significant inverse correlation was observed between Mercuri scores and MRC grading as well as MDFRS scores. A direct linear correlation was observed between duration of illness and fibro-fatty changes in piriformis, quadriceps and superficial posterior leg muscles. There was no correlation between MRI findings and genotypic characteristics. However, this specific pattern of muscle involvement in MRI could aid in proceeding for genetic testing when clinical suspicion is high, thus reducing the need for muscle biopsy. Fibro fatty infiltration as measured by Mercuri scoring can be a useful marker for assessing the disease severity and progression. PMID- 27666776 TI - COPD, emphysema and the onset of lung cancer. A systematic review. AB - Chronic Obstructive Pulmonary Disease (COPD) and emphysema have been described as possible risk factors for lung cancer. We aim to assess the relationship between COPD, emphysema and the onset of lung cancer. We have developed a systematic review of the published literature in order to systematically analyze the scientific evidence available on this association, applying predefined inclusion and exclusion criteria. 11 Studies were included. Both COPD and emphysema seem to increase the risk of developing lung cancer, being this risk higher for smokers with heavier tobacco consumption. These results emphasize the need for physicians to perform spirometries in current and former smokers and lung image tests when needed in order to identify COPD and emphysema and thus select patients at higher risk of developing lung cancer. PMID- 27666777 TI - The heparanase/heparan sulfate proteoglycan axis: A potential new therapeutic target in sarcomas. AB - Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression. The clinical management of advanced diseases remains a challenge. In several sarcoma subtypes, high levels of heparanase expression have been correlated with poor prognosis associated factors. On the other hand, expression of cell surface-associated HSPGs (i.e. glypicans and syndecans) has been found altered in specific sarcoma subtypes. Recent studies provided the preclinical proof-of-principle of the role of the heparanase/HSPG axis as therapeutic target in various sarcoma subtypes. Although currently there are no clinical trials evaluating agents targeting heparanase and/or HSPGs in sarcomas, we here provide arguments for this strategy as potentially able to implement the therapeutic options for sarcoma patients. PMID- 27666778 TI - Natural Anaplasmataceae infection in Rhipicephalus bursa ticks collected from sheep in the French Basque Country. AB - Rhipicephalus bursa is one of 79 species of the genus Rhipicephalus in the family of Ixodidae. In this study, we investigated Anaplasmataceae bacteria associated with R. bursa collected after an epizootic outbreak of ovine anaplasmosis. 76 adult ticks, (60 male and 16 female ticks), were removed from sheep in two farms and all identified as R. bursa, all females were partially engorged. We found that 50% of the ticks were positive in the initial Anaplasmataceae qPCR screening. Bacterial species was identified by analyzing the sequences of amplicons of 23S rRNA, groEL and rpoB genes. 22.4% of ticks contained DNA of Anaplasma phagocytophilum and 7.9% the DNA of Anaplasma ovis. Based on 23S rRNA and groEL genes analysis, we found that 19.7% of ticks contained a potentially new species of Ehrlichia. We propose the status of Candidatus for this uncultured species and we provisionally name it Candidatus Ehrlichia urmitei. No Wolbachia were identified. These results show that R. bursa can be a carrier of Anaplasmataceae bacteria. PMID- 27666779 TI - Exploring Spinal Cord Protection by Remote Ischemic Preconditioning: An Experimental Study. AB - BACKGROUND: Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. METHODS: The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery. All animals underwent systematic closure of the left subclavian artery and segmental arteries of the descending thoracic aorta to the level of diaphragm. Motor-evoked potential monitoring was performed in both hind limbs. Continuous electrocardiogram and hemodynamics were monitored, and pulmonary artery blood samples were collected. A neurologic assessment was performed 6 hours after the procedure. The thoracic and lumbar portions of the spinal cord were collected for histologic and immunohistochemical analysis. RESULTS: The bilateral motor-evoked potential amplitude responses were higher in the RIPC group (p < 0.05) than in the control group; the difference was detected already before spinal cord ischemia. Paraplegia occurred in 1 control animal. Immunohistochemical total scores of antioxidant response regulator nuclear factor erythroid 2-related factor 2 were better in the RIPC group (11.0; range, 8.5 to 14.0) than in the control group (5.2; range, 1.0 to 9.0; p = 0.023). CONCLUSIONS: RIPC induces electrophysiologic changes in the central nervous system that may confer spinal cord protection extending the resistance to ischemia. The significantly higher nuclear factor erythroid 2-related factor 2 scores suggest better neuronal cell protection against oxidative stress in the RIPC group. PMID- 27666781 TI - Serial Lactate Measurements as a Prognostic Tool in Venovenous Extracorporeal Membrane Oxygenation Support. AB - BACKGROUND: Serial lactate measurements over time or lactate clearance has been reported to be clinically reliable for risk stratification in different pathologic conditions ranging from sepsis to trauma, but no data are so far available on the behavior of lactate during venovenous extracorporeal membrane oxygenation (VV-ECMO) support in refractory adult acute respiratory distress syndrome (ARDS). METHODS: We assessed lactate values during VV-ECMO support and the prognostic role of lactate clearance at 6, 24, and 72 hours after ECMO start in 126 consecutive patients with refractory ARDS treated with VV-ECMO. RESULTS: Survivors showed a progressive, significant decrease in lactate values throughout the study period, whereas nonsurvivors exhibited a progressive increase. Lactate values (measured before ECMO initiation, as well as 6 and 24 hours after) were independently associated with intensive care unit (ICU) death. A significantly higher lactate clearance was observed for survivors at 72 hours after ECMO start than for nonsurvivors. At logistic regression analysis, lactate clearance at 72 hours after ECMO start was an independent predictor of ICU death (odds ratio 0.988, 95% confidence interval [CI]: 0.995 to 0.982, p = 0.001) (together with age, body mass index, and Sequential Organ Failure Assessment). At receiver operating characteristic curve analysis, lactate clearance at 72 hours after ECMO start cutoff value of -16% had a sensitivity of 68% and a specificity of 63% (area under the curve = 0.67, 95% CI: 0.57 to 0.77, p = 0.002). CONCLUSIONS: Lactate (measured before ECMO initiation, as well as 6 and 24 hours after) is a prognostic factor in patients with refractory ARDS treated with VV-ECMO, and lactate clearance at 72 hours after ECMO initiation helps in the risk stratification of these patients, being independently associated with death. PMID- 27666780 TI - Granular Media Calcinosis in the Aortic Walls of Patients With Bicuspid and Tricuspid Aortic Valves. AB - BACKGROUND: Bicuspid aortic valve (BAV), the most frequent congenital cardiac abnormality, is associated with a higher risk for ascending aortic aneurysms and aorta-related complications (ie, dissection and rupture). The aim of this study was to quantify granular media calcinosis (GMC) in the ascending aortic wall of patients with BAV. METHODS: We analyzed samples of the ascending aorta from patients with BAV (n = 54) and patients with tricuspid aortic valve (TAV) (n = 33) who underwent aortic repair, regarding medial thickness and diameter expansion. Additionally, the convexity and concavity of the samples were stained for GMC and elastin fragmentation. RESULTS: The quantitative analysis revealed a significantly higher extent of GMC in patients with BAV at the aortic convexity and concavity compared with patients with TAV, independent of aortic diameter. Additionally, GMC increased with enlargement of the aortic diameter in patients with BAV. Furthermore, we found a significantly reduced total medial thickness in patients with BAV compared with patients with TAV. CONCLUSIONS: Our findings highlight GMC as a prominent feature of bicuspid aortopathy. PMID- 27666782 TI - Planned Versus Unplanned Reexplorations for Bleeding: A Comparison of Morbidity and Mortality. AB - BACKGROUND: Mediastinal reexplorations for bleeding are associated with significant morbidity and mortality. This study hypothesized that bleeding patients who undergo delayed chest closure after an initial operation experience similar outcomes in comparison with patients who have initial chest closure and later require an unplanned reexploration. METHODS: This study included all patients in the Johns Hopkins University School of Medicine (Baltimore, MD) institutional Society of Thoracic Surgeons (STS) database who underwent cardiac surgical procedures or thoracic transplantation from 2011 to June 2014, had an intraoperative red blood cell transfusion requirement of 2 units or more, and required mediastinal reexploration for bleeding. Reexplorations were classified as planned (temporary chest closure for a planned "second look") or unplanned (initial sternal closure and subsequent reexploration). The two groups were then propensity matched. The primary outcome was 30-day mortality. Secondary outcomes were major complication rates, hospital length of stay, duration of mechanical ventilation, and incidence of postoperative pneumonia and cardiac arrest. RESULTS: Among 3,293 patients, 110 (3.3%) met inclusion criteria and required mediastinal reexploration for bleeding. This group included 62 planned (56%) and 48 unplanned (44%) reexplorations. After propensity matching 30 pairs of patients across 16 variables, operative mortality rates were comparable (37% vs 37%; p = 1.00) between unplanned and planned reexploration cohorts. There were no differences in rates of deep sternal wound infection, renal failure, postoperative hospital length of stay, pneumonia, or cardiac arrest, with the exception of a higher rate of prolonged intubation (93% vs 53%; p < 0.01) in the planned reexploration group. CONCLUSIONS: Delayed sternal closure is a safe alternative to initial definitive chest closure when concern exists for postoperative bleeding. PMID- 27666783 TI - Severity of Preoperative Aortic Regurgitation Does Not Impact Valve Durability of Aortic Valve Repair Following the David V Valve Sparing Aortic Root Replacement. AB - BACKGROUND: The David V valve-sparing aortic root replacement (VSRR) is an established and durable method of root reconstruction for varying pathologies. However, the impact of the severity of preoperative aortic regurgitation (AR) on long-term durability remains unclear. The purpose of this research was to investigate the impact of the degree of preoperative AR on midterm durability following VSRR. METHODS: A retrospective review of the adult cardiac surgical database at a single academic center was undertaken from 2005 to 2015 for 223 adult patients who underwent VSRR. Patients were followed annually with echocardiograms, and a prospectively maintained database kept track of patient data. Follow-up was 97.7% complete, and the median echocardiographic follow-up was 25.5 months (range, 1 to 123 months). Patients with preoperative AR less than or equal to 2 were compared with patients with AR greater than 2 to determine the impact of preoperative AR upon valve repair durability. RESULTS: There were 223 patients who underwent VSRR during the study period, including 114 (51.1%) who required concomitant cusp repair. The operative mortality was 5 (2.2%). Ninety seven patients (43.5%) had preoperative AR greater than 2. A total of 213 patients (95.5%) were available for long-term follow-up; of these patients, 7 (3.3%) had AR greater than 2. Fifty-two patients had a bicuspid aortic valve (22 AR <=2 and 30 AR >2; p = 0.02). Patients with preoperative AR greater than 2 experienced greater reverse left ventricular remodeling and increases in left ventricular ejection fraction than did patients with preoperative AR less than or equal to 2 (p < 0.01). The midterm freedom from AR greater than 2 was similar for both preoperative AR groups (p = 0.57). The 8-year freedom from AR greater than 2 was 89.1% (95% confidence interval, 55.3% to 97.8%) for patients with preoperative AR less than or equal to 2 and 92.7% (95% confidence interval, 78.8% to 97.6%) for preoperative AR greater than 2. Five patients (2.4%) required aortic valve replacement during the follow-up period (3 preoperative AR <=2, 2 preoperative AR >2). CONCLUSIONS: VSRR remains an effective and durable treatment for severe AR and preserved leaflet architecture. The severity of preoperative AR does not appear to impact midterm freedom from moderate to severe AR. VSRR results in significant left ventricular remodeling in patients with preoperative AR greater than 2. PMID- 27666784 TI - When Should the Mitral Valve Be Repaired or Replaced in Patients With Ischemic Mitral Regurgitation? AB - BACKGROUND: Data comparing outcomes after repair versus replacement of chronic ischemic mitral regurgitation (MR) is evolving. Recent data suggest that repair is associated with recurrent MR, but not survival, when compared with replacement. However, it remains unclear when either surgical strategy should be applied based on preoperative mitral valve anatomy. METHODS: Between 2001 and 2013, 161 patients underwent repair or replacement of chronic ischemic MR. The mean age of these patients was 68.2 +/- 9.0 years, 44 (27%) were female, and concomitant coronary artery bypass grafting was performed in 126 (78%). The mean preoperative posterior leaflet angle was 27.7 +/- 14.2 degrees, and the left ventricular ejection fraction was 41.2 +/- 12.4%. Detailed preoperative assessments of mitral valve anatomy were determined by transesophageal echocardiography. Clinical and echocardiographic follow-up was for 4.6 +/- 3.2 years and extended to 11.7 years. RESULTS: Overall, perioperative death occurred in 6 (3.3%) patients; 2 patients died after valve repair and 4 after valve replacement. Five-year survival and freedom from recurrent MR (>=2+) rates were 74.0 +/- 5.6% and 57.8 +/- 8.0%, respectively, after valve repair and 69.4 +/- 6.2% and 87.1 +/- 7.0%, respectively, after valve replacement. Valve repair was associated with recurrent MR (>=2+) (hazard ratio [HR], 5.3 +/- 3.3; p = 0.007), but not survival (HR, 0.9 +/- 0.3; p = 0.8). Preoperative posterior leaflet tethering angle was associated with survival (HR, 1.09 +/- 0.04; p = 0.005) and also recurrent MR (>=2+) (HR, 1.04 +/- 0.02; p = 0.03) after valve repair. Based on a receiver operator curve describing the relationship between recurrent MR (>=2+) and posterior leaflet tethering angle, a threshold of 22 degrees was determined. CONCLUSIONS: Surgical correction of chronic ischemic MR can be performed with favorable early and late results, although recurrent MR occurred more often after repair. Among patients who underwent repair of ischemic MR, a preoperative posterior leaflet tethering angle of 22 degrees or greater was associated with worse late outcomes. PMID- 27666786 TI - Self-Reported Physical Quality of Life Before Thoracic Operations Is Associated With Long-Term Survival. AB - BACKGROUND: The aim was to analyze the association between baseline self-reported health-related quality of life and long-term survival after thoracic operations. METHODS: In a prospective population-based cohort study, we included patients scheduled for thoracic operations and obtained information about preoperative health-related quality of life using the validated quality-of-life instrument Short Form-36. Patients were categorized according to higher or lower physical and mental component scores, compared with an age- and sex-matched reference population. The primary outcome measure was all-cause mortality and was ascertained from Swedish national registers. We used Cox regression for estimation of hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between preoperative physical/mental quality of life and long-term survival while adjusting for differences in baseline characteristics, cancer stage, histopathologic process, and other factors. RESULTS: We included 249 patients between 2006 and 2008. During a median follow-up time of 8.0 years, 119 patients (48%) died. Having a physical component summary score less than reference was significantly associated with mortality (multivariable adjusted HR 2.02, 95% CI: 1.34 to 3.06, p = 0.001). A mental component summary score less than reference was not associated with mortality (adjusted HR 1.32, 95% CI: 0.84 to 3.06, p = 0.233). CONCLUSIONS: In patients who underwent thoracic operations, a self-reported physical quality of life lower than reference value was associated with significantly worse survival independent of histopathologic process, cancer stage, extent of operations, and other patient-related factors. The preoperative mental component of quality of life was not associated with long term survival. PMID- 27666785 TI - Central Repair With Antegrade TEVAR for Malperfusion Syndromes in Acute Debakey I Aortic Dissection. AB - BACKGROUND: In acute DeBakey I aortic dissection presenting with malperfusion syndromes, we assessed whether standard open repair with concomitant antegrade stent grafting (thoracic endovascular aneurysm repair; TEVAR) of the descending thoracic aorta (DTA) improves outcomes compared with standard repair alone. METHODS: From 2005 to 2012, 277 patients with acute DeBakey I dissection underwent emergent operation. Of these, 104 patients (37%) presenting with end organ malperfusion were divided into those undergoing standard distal repair entailing transverse hemiarch replacement (Standard group, n = 65) versus standard repair with concomitant DTA TEVAR during circulatory arrest (TEVAR group, n = 39). Prospectively maintained aortic dissection database was retrospectively reviewed. RESULTS: Demographic characteristics and preoperative comorbidities were similar. Circulatory arrest (56 +/- 12 versus 34 +/- 14 minutes, p < 0.001) and cross-clamp (176 +/- 43 versus 119 +/- 80, p = 0.001) times were longer in the TEVAR group. Overall, postoperative stroke rate (5% [n = 2] versus 6% [n = 4], p = 1), paraplegia rate (5% [n = 2] versus 5% [n = 3], p = 1.0), and renal failure rate (10% [n = 4] versus 22% [n = 14], p = 0.2) were similar. In-hospital/30-day mortality rate was lower in the TEVAR group but was not significant (18% (n = 7) versus 34% [n = 22], p = 0.1). In patients presenting with malperfusion involving greater than one end-organ system, the mortality rate was significantly improved in the TEVAR group (28% [n = 6] versus 58% [n = 14], p = 0.05). CONCLUSIONS: Standard repair with antegrade TEVAR of the DTA for acute DeBakey I aortic dissection presenting with malperfusion syndromes can be safely performed. Further, true lumen stabilization achieved through DTA TEVAR may provide a survival benefit in patients with distal multiorgan malperfusion. PMID- 27666787 TI - Extracorporeal membrane oxygenation for the treatment of postcardiotomy shock. AB - Use of extracorporeal membrane oxygenation (ECMO), one of an increasing variety of mechanical circulatory support strategies, was first used close to 50 years ago. For decades, it was mostly applied to the pediatric population. However, during the past several years, its use has dramatically increased as therapy for pulmonary and cardiac failure in the adult. In particular, ECMO is being used more and more for postcardiotomy shock. Unfortunately, despite its increased application in this setting, improved outcomes have been hard to come by. Improved results must be grounded on an approach that honors the tenets of myocardial recovery, minimizing the work done by the heart during the recovery period. Left ventricular decompression should be a tenet of ECMO support in the setting of postcardiotomy shock, universally applied if we are to see any significant improvement in our results. Furthermore, the point is made that surgeons should play a leadership role in the immediate counseling of patients' families to assure realistic expectations on their part. To address the need for family support during this very difficult time, ECMO centers should design a programmatic approach to care for patients and their families so as to provide them with education, guidance, and emotional support. PMID- 27666788 TI - Enhancement and Passive Acoustic Mapping of Cavitation from Fluorescently Tagged Magnetic Resonance-Visible Magnetic Microbubbles In Vivo. AB - Previous work has indicated the potential of magnetically functionalized microbubbles to localize and enhance cavitation activity under focused ultrasound exposure in vitro. The aim of this study was to investigate magnetic targeting of microbubbles for promotion of cavitation in vivo. Fluorescently labelled magnetic microbubbles were administered intravenously in a murine xenograft model. Cavitation was induced using a 0.5-MHz focused ultrasound transducer at peak negative focal pressures of 1.2-2.0 MPa and monitored in real-time using B-mode imaging and passive acoustic mapping. Magnetic targeting was found to increase the amplitude of the cavitation signal by approximately 50% compared with untargeted bubbles. Post-exposure magnetic resonance imaging indicated deposition of magnetic nanoparticles in tumours. Magnetic targeting was similarly associated with increased fluorescence intensity in the tumours after the experiments. These results suggest that magnetic targeting could potentially be used to improve delivery of cavitation-mediated therapy and that passive acoustic mapping could be used for real-time monitoring of this process. PMID- 27666789 TI - Pretreatment with a gamma-Secretase Inhibitor Prevents Tumor-like Overgrowth in Human iPSC-Derived Transplants for Spinal Cord Injury. AB - Neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of gamma-secretase inhibitor (GSI) and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine. PMID- 27666790 TI - Development and Dynamic Regulation of Mitochondrial Network in Human Midbrain Dopaminergic Neurons Differentiated from iPSCs. AB - Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed differentiation of hiPSCs to DA neurons, mitochondria in these neurons exhibit pronounced changes during differentiation, including mature neurophysiology characterization and functional synaptic network formation. Inhibition of mitochondrial respiratory chains via application of complex IV inhibitor KCN (potassium cyanide) or complex I inhibitor rotenone restricted neurogenesis of DA neurons. These results demonstrated the direct importance of mitochondrial development and bioenergetics in DA neuronal differentiation. Our study also provides a neurophysiologic model of mitochondrial involvement in neurogenesis, which will enhance our understanding of the role of mitochondrial dysfunctions in neurodegenerative diseases. PMID- 27666793 TI - WITHDRAWN: Clinical pathways inference from decision rules by hybrid stream mining and fuzzy unordered rule induction strategy. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27666792 TI - Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone. AB - Identifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs) is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh) signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zone (V-SVZ), one of the main brain neurogenic niches. Specific deletion of the Hh receptor Patched in NSCs during adulthood upregulated Hh signaling in quiescent NSCs, progressively leading to a large accumulation of these cells in the V-SVZ. The pool of non neurogenic astrocytes was not modified, whereas the activated NSC pool increased after a short period, before progressively becoming exhausted. We also showed that Sonic Hedgehog regulates proliferation of activated NSCs in vivo and shortens both their G1 and S-G2/M phases in culture. These data demonstrate that Hh orchestrates the balance between quiescent and activated NSCs, with important implications for understanding adult neurogenesis under normal homeostatic conditions or during injury. PMID- 27666794 TI - WITHDRAWN: Benchmarking swarm intelligence clustering algorithms with case study of medical data. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27666791 TI - Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency. AB - Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming "boosters" also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL rearranged B-ALL to reprogramming into pluripotency. PMID- 27666795 TI - Heritability of startle reactivity and affect modified startle. AB - Startle reflex and affect-modified startle reflex are used as indicators of defensive reactivity and emotional processing, respectively. The present study investigated the heritability of both the startle blink reflex and affect modification of this reflex in a community sample of 772 twins ages 14-15years old. Subjects were shown affective picture slides falling in three valence categories: negative, positive and neutral; crossed with two arousal categories: high arousal and low arousal. Some of these slides were accompanied with a loud startling noise. Results suggested sex differences in mean levels of startle reflex as well as in proportions of variance explained by genetic and environmental factors. Females had higher mean startle blink amplitudes for each valence-arousal slide category, indicating greater baseline defensive reactivity compared to males. Startle blink reflex in males was significantly heritable (49%), whereas in females, variance was explained primarily by shared environmental factors (53%) and non-shared environmental factors (41%). Heritability of affect modified startle (AMS) was found to be negligible in both males and females. These results suggest sex differences in the etiology of startle reactivity, while questioning the utility of the startle paradigm for understanding the genetic basis of emotional processing. PMID- 27666796 TI - Gender-specific Differences in Great Saphenous Vein Conduit. A Link to Lower Extremity Bypass Outcomes Disparities? AB - BACKGROUND: Inferior lower extremity bypass (LEB) outcomes have been reported among women with peripheral arterial disease (PAD), but the mechanisms responsible for this disparity are unknown. Great saphenous vein (GSV) is considered the conduit of choice for LEB; GSV diameter is associated with graft patency and therefore is often used as a criterion for suitability for use as bypass conduit. We hypothesized that gender-based differences in GSV may contribute to LEB outcomes disparities. To explore this hypothesis, we performed a gender-based analysis of GSV anatomic characteristics among patients with PAD who were studied with duplex ultrasound vein mapping during evaluation for LEB. METHODS: Consecutive patients undergoing ultrasound vein mapping for planned LEB were analyzed. Minimum above- and below-knee GSV diameters were obtained in addition to demographic, procedural, and clinical data. Associations between gender and GSV diameter were evaluated using multivariate mixed models adjusting for anatomic location and within-patient correlation. RESULTS: One hundred five patients were analyzed. Mean patient age was 65 +/- 11 years, 25% were women, and 78% were white. Mixed model estimates of minimum GSV diameters were 3.14 +/- 0.09 mm above knee and 2.74 +/- 0.09 below knee for men versus 3.23 +/- 0.14 above knee and 2.49 +/- 0.14 below knee for women. A gender-based interaction between anatomic location and GSV diameter was identified, with women having a greater difference between above- and below-knee GSV diameters (or taper; mean difference of 0.73 +/- 0.12 vs. 0.41 +/- 0.17 mm; P = 0.017). CONCLUSIONS: GSV taper (difference between above- and below-knee diameters) is greater in women and may contribute to inferior patency after LEB with vein conduit, particularly for below-knee target vessels. Further research is necessary to evaluate specific hemodynamic effects of graft taper and links with other clinical endpoints. In addition to minimum diameter, vein graft taper may warrant consideration when planning LEB. PMID- 27666797 TI - Juxtarenal Inflammatory Aneurysm Treated with Bilateral Iliac-Renal Bypass Using the Gore Hybrid Device and Total Sealing of the Aneurysmal Sac with a Nellix Device. AB - The aim of this study is to present the treatment of a juxtarenal inflammatory aneurysm using a Nellix device (Endologix, Inc., Irvine, CA) to seal the entire aneurysmatic aorta combined with bilateral iliac-renal bypass using the Gore hybrid vascular graft (W. L. Gore & Associates, Inc., Flagstaff, AZ). A 63-year old man was diagnosed with a 6-cm juxtarenal inflammatory aneurysm. It was initially decided to treat him with an aorto-aortic bypass and to revascularize the 2 renal arteries with "graft to renal artery bypass" using Gore hybrid vascular grafts. Due to the high intraoperative bleeding preparing the proximal neck and the tight adhesion of the aorta to the adjacent structures, we decided to change our plans and to treat the patient using the Nellix system combined with bilateral iliac-renal bypass using the Gore hybrid vascular grafts. Contrast computed tomography control at 1 month showed complete sealing of the aneurysm sac and patent iliac renal bypasses. The reported case demonstrated that the Nellix Endovascular Aneurysm Sealing system combined with Gore hybrid vascular grafts for bilateral iliac-renal bypass showed that it can be an effective modality for the treatment of juxtarenal, inflammatory aortic aneurysm and revascularization of the renal arteries from the distal iliac arteries. PMID- 27666798 TI - Mastication Steal Syndrome. AB - A 56-year-old woman presented with episodic vertigo, dizziness, and diplopia during meals and prolonged verbal presentations at work. Subsequent work-up included an eventual catheter-based angiogram revealing an ostial left external carotid artery (ECA) occlusion with reconstituted retrograde flow via a variant collateral branch from the dominant left vertebral artery. The findings demonstrate that repetitive activities involving craniofacial muscular systems supplied by the ECA result in a symptomatic arterial steal syndrome via the enhanced diverted flow from the collateral vertebral-basilar arterial system. A left ECA endarterectomy with reimplantation of the vessel was performed, and the patient has been episode free thereafter. PMID- 27666799 TI - Acute Vasodilation Caused by Different Strategies of Renal Sympathetic Denervation for Right and Left Renal Arteries. PMID- 27666801 TI - Pulsatile Varicose Veins Secondary to Severe Tricuspid Regurgitation: Report of a Case Successfully Managed by Endovenous Laser Treatment. AB - We report a case of pulsatile varicose veins successfully managed by endovenous laser treatment (EVLT) of the great saphenous vein (GSV). A 77-year-old woman taking an anticoagulant was transferred to our hospital for pulsatile varicose veins complicated with repeated venous bleeding from an ulcer of her left lower leg. Doppler echocardiography showed severe tricuspid regurgitation, and duplex ultrasonography revealed an arterial-like pulsating flow in the saphenofemoral junction and along the GSV, but an arteriovenous fistula, obstruction of the deep veins, and the distal incompetent perforators were not detected. Because of a significant bleeding risk due to elevated venous pressure and anticoagulant therapy, EVLT was performed for the GSV, which resulted in the complete occlusion of the GSV and healing of the ulcer. EVLT presents a safe and useful therapeutic technique for pulsatile varicose veins in the limbs. PMID- 27666800 TI - The Superficial Femoral Artery: An Alternative Access for Percutaneous Endovascular Aneurysm Repair. AB - BACKGROUND: The aim of this study was to report the results of percutaneous endovascular aortic aneurysm repair (PEVAR) using the superficial femoral artery (SFA) for large bore vessel access. METHODS: We reviewed all PEVAR procedures at our institution over an 18-month period, identifying all patients who underwent PEVAR with the use of one or both SFAs for endograft delivery with dual ProGlide large bore access closure. Indications for use of the SFA instead of the common femoral artery (CFA) included morbid obesity, CFA vessel wall disease, and scarring from previous CFA surgery. RESULTS: In total, 158 percutaneous access closures were performed in 79 patients. Ten patients had one or both SFAs used. We accessed a total of 13 SFAs: 6 for the endograft main body (size range 18- to 20-French) and 7 for the limb (14- to 16-French). The freedom from open conversion was 84.6%. In comparison, of 145 CFA accesses (in 76 patients) there were 9 conversions (93.7% success). Of the 13 SFAs accessed, there were no major access site complications (pseudoaneurysm, access site bleed, limb ischemia, or need to return to the operating room). All SFAs accessed remained patent at the latest follow-up (range 1-13 months, median 8 months). CONCLUSIONS: Our preliminary case series suggests that, in the absence of a healthy or percutaneously accessible CFA, a healthy SFA may be considered for PEVAR access. While likely carrying a higher risk of open conversion, this technique, when combined with intraoperative duplex ultrasound (both before and after the procedure) and with meticulous ultrasound-guided vascular access, appears safe for up to 20-French device diameters. PMID- 27666802 TI - Initial Experiences with Endovascular Management of Submassive Pulmonary Embolism: Is It Safe? AB - BACKGROUND: Interventional strategies for massive and submassive pulmonary embolism (smPE) have historically included either systematic intravenous thrombolytic alteplase or surgical embolectomy, both of which are associated with significant morbidity and mortality. However, with the advent of endovascular techniques, recent studies have suggested that an endovascular approach to the treatment of acute smPE may be both safe and effective with excellent outcomes. The purpose of this study was to evaluate the outcomes of patients who have undergone catheter-directed thrombolysis (CDT) for smPE at our institution in an effort to determine the safety of the procedure. METHODS: A retrospective review was conducted from December 2012 to June 2015 to identify patients whom underwent CDT in the treatment of a smPE at our institution. Primary measure was safety of the procedure. Outcome variables were classified as serious or minor adverse events. Serious events included death, stroke, myocardial infarction, and bleeding complications requiring surgical intervention or transfusion. Minor events included groin hematoma, development of arteriovenous fistula, and bleeding requiring interruption or cessation of CDT. In addition, a secondary measure included effectiveness of CDT based on preinterventional and postinterventional clinical examination and radiographic findings. RESULTS: A total of 27 patients undergoing CDT for smPE at our institution were evaluated. The standard procedure included access via bilateral femoral veins and placement of bilateral EKOS catheters for ultrasound-assisted thrombolysis (USAT), with Activase (alteplase) at 1 mg per hour in each catheter for a total of 12 hr. There were no serious adverse events and only 4 patients (14.8%) had minor events, of which only 1 patient required premature termination of therapy due to bleeding resulting in a 3.7% clinically relevant bleeding rate. In addition, a reduction in a right-to-left ventricular end-diastolic diameter ratio (RV/LV ratio) on follow-up imaging was observed in each of the 18 patients where preinterventional and postinterventional imaging was available. Likewise, via chart review, all patients reported significant cessation of shortness-of-breath and resolution of chest pain with associated decrease in supplemental oxygen requirement. CONCLUSIONS: Current evidence, the majority of which has been industry funded, suggests that CDT should be considered as the first-line therapy for smPE. Our experience, in this single-institution retrospective review, demonstrates that CDT with USAT in the treatment of smPE is safe, while providing immediate resolution of both RV strain and clinical symptoms such as shortness-of breath and chest pain. We hope that these data will allow other institutions to consider CDT as a plausible option in the treatment of smPE. PMID- 27666803 TI - Outcome of Surgical Treatment for Thoracic Outlet Syndrome: Systematic Review and Meta-Analysis. AB - BACKGROUND: Many publications report outcomes of surgical treatment for thoracic outlet syndrome (TOS); however, high-quality reviews and meta-analyses are lacking. This systematic review and meta-analysis summarizes and compares the outcomes and major complications of the surgical procedures for the 3 types of TOS: arterial, venous, and neurogenic. METHODS: MEDLINE, EMBASE, and CINAHL databases, and the Cochrane Database of Systematic Reviews were searched for papers published between January 1980 and February 2015, using the keywords thoracic outlet syndrome, and treatment and surgical. Articles were eligible for inclusion if the following criteria were met: studies describing outcomes of surgery for TOS, published in English, human studies, and available full-text. The exclusion criteria were case-series and case reports (n < 5), reviews, abstracts, and studies of endoscopic-assisted or robotic endoscopic-assisted transaxillary first rib resection. RESULTS: A total of 12 papers met our inclusion criteria and were finally included in this systematic review. All included articles showed improvement of complaints after surgical treatment. In our meta-analysis, improvement to Derkash's classification category excellent/good was achieved in 90% of the arterial and venous TOS groups. Preoperative and postoperative Disabilities of the Arm, Shoulder, and Hand scores show improvement of 28.3 points after operative treatment of neurogenic TOS. CONCLUSIONS: In conclusion, surgical treatment of TOS seems to be beneficial in most patients and is relatively safe. The largest challenge remains the diagnosis of TOS, especially neurogenic TOS, because standardized diagnostic criteria are lacking. Future studies should focus on the diagnostic work-up of TOS. PMID- 27666804 TI - Management of Modifiable Vascular Risk Factors Improves Late Survival following Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The main determinants of survival following abdominal aortic aneurysm (AAA) repair are preexisting risk factors rather than the method of repair chosen. The main aim of this meta-analysis was to assess the effect of modifiable risk factors on late survival following AAA repair. METHODS: Electronic databases were searched to identify all relevant articles reporting the influence of modifiable risk factors on long-term survival (>=1 year) following elective open aneurysm repair and endovascular aneurysm repair. RESULTS: Twenty-four studies which comprised 53,118 patients, published between 1989 and 2015, were included in the analysis. The use of statin, aspirin, beta-blockers, and a higher hemoglobin level was all significant predictors of improved survival following repair with a hazard ratio (HR) and 95% confidence interval (CI) of 0.75 (0.70 0.80), 0.81 (0.73-0.89), 0.75 (0.61-0.93), and 0.84 (0.74-0.96), respectively. Smoking history and uncorrected coronary disease were associated with a worse long-term survival of HR 1.27 (95% CI 1.07-1.51) and HR 2.59 (95% CI 1.14-5.88), respectively. CONCLUSIONS: Addressing cardiovascular risk factors in patients preoperatively improves long-term survival following AAA repair. Global strategies to improve risk factor modifications in these patients are warranted to optimize long-term outcomes. PMID- 27666805 TI - Endovascular Treatment of Late Aortic Erosive Lesion by Pedicle Screw without Screw Removal: Case Report and Literature Review. AB - BACKGROUND: Aortic lesions are uncommon complications in spine surgery, but potentially fatal, because they can cause massive bleeding and hemodynamic instability. We report the endovascular treatment of late aortic erosive lesion by pedicle screw without screw removal. METHODS: A breast cancer patient had a pathological fracture on T10, with spinal cord compression, and a pseudoaneurysm of the aorta in contact with an anterolateral pedicle screw. Endovascular surgery corrected the aortic lesion and allowed decompression, a week later, by posterior arthrodesis (T7-L1), with screw maintenance. RESULTS: There was no contrast leakage at thorax angiotomography in 2 years, and she died of meningeal carcinomatosis. CONCLUSION: Screw maintenance was safe in the endovascular treatment of aortic lesion by erosion. PMID- 27666806 TI - Open Repair for Abdominal Aortic Aneurysm in a Young Boy with Tuberous Sclerosis and Review of the Literature. AB - BACKGROUND: Abdominal aortic aneurysms (AAAs) are very rare in pediatric patients and can rarely be associated with tuberous sclerosis (TS). Open surgery is the first-line therapy. We report our experience added by a review on current literature. CASE REPORT: A 9-year-old boy with TS and history of 2 earlier open repairs for AAA presented to our department with a recurrent juxtarenal aortic aneurysm. We performed a polytetraflourethylene patch plasty. Postoperative course was uneventful. After 8 months, reconstruction was stable, and no recurrent aneurysm developed. CONCLUSIONS: Recurrent aneurysms may develop after open surgery for TS-associated AAA. However, open surgery is the recommended therapy but requires special techniques and experience in pediatric patients. PMID- 27666807 TI - Abdominal Aortic Surgery in the Presence of Inferior Vena Cava Anomalies: A Case Series. AB - BACKGROUND: Left-sided inferior vena cava (LIVC) and duplicated inferior vena cava (DIVC) are rare asymptomatic congenital abnormalities. Unrecognized, these anomalies can be the source of major injuries and cause serious life-threatening bleeding complications especially during abdominal aortic surgery. METHODS: Retrospective data for patients with 2 major inferior vena cava (IVC) anomalies that underwent aortic surgery over a 13-year period were collected. Patient demographics, type of aortic disease and caval anomaly, surgical approach, type of aortic reconstruction associated with procedure on caval vein, postoperative complications, and in-hospital mortality were recorded. RESULTS: There were 9 patients with inferior vena cava (IVC) anomalies who underwent aortic surgery. All of them were men, with a median age of 66.2 years. Seven had an LIVC and 2 had DIVC. Five patients were operated on due to abdominal aortic aneurysm and 4 due to aortoiliac occlusive disease. In all patients, a midline transperitoneal aortic approach was performed. In 5 cases, the left IVC had to be temporarily resected and later reconstructed, and in the other 4 it was just mobilized. There were no postoperative complications except in one patient who developed deep vein thrombosis in the left calf; this was successfully treated with anticoagulant therapy. CONCLUSION: Due to favorable results and low incidence of perioperative complications and in the absence of other associated abdominal pathology, we propose the midline transperitoneal approach with mobilization or temporary resection of LIVC. PMID- 27666808 TI - The Influence of Collagen Impregnation of a Knitted Dacron Patch Used in Carotid Endarterectomy. AB - BACKGROUND: In selected populations, carotid endarterectomy (CEA) reduces long term stroke risk. Studies have shown increased risk of restenosis with use of a collagen-impregnated Dacron patch compared to a polytetrafluorethylene patch. There is concern that collagen impregnation may initiate thrombosis or promote restenosis due to platelet activation. We performed a retrospective analysis of our CEA experience with routine patching using knitted Dacron patches with (Hemashield) and without (Sauvage) collagen impregnation. METHODS: Our database was queried for all CEAs between January 2006 and December 2010. Seven surgeons performed 655 CEAs. Patients were excluded if no patch was used (n = 1), a primary CEA was performed before study period or by other surgeons (n = 11), or the patch type was indeterminable (n = 38). Demographics, clinical data, and outcomes were compared between the collagen-impregnated (C, Hemashield) group and non-collagen-impregnated (NC, Sauvage) group. RESULTS: A total of 605 CEAs were analyzed (395 C and 210 NC). Demographics were similar except for coronary artery disease (C 54.3% vs. NC 41.6%, P = 0.003). There was no statistically significant difference in 30-day (C 99.7% vs. NC 99.5%, P > 0.99) or 5-year survival (C 80.0% vs. NC 83.7%, P = 0.26) or 30-day stroke rate (C 0.3% vs. NC 1.0%, P = 0.28). No late ipsilateral strokes occurred during 5-year follow-up. The 5-year freedom from restenosis >30% (C 85.3% vs. NC 86.4%, P = 0.33), restenosis >50% (C 94.5% vs. NC 95.5%, P = 0.44), and restenosis >70% (C 98.6% vs. NC 98.9%, P = 0.73) were similar. Two patients underwent carotid stenting for restenosis >70%. Two patients (both in the C group) developed occlusion of the carotid artery. CONCLUSIONS: The thrombosis and restenosis rates in the 2 groups were similar. This suggests that collagen-impregnated patches do not initiate thrombosis or increase restenosis rates after CEA. PMID- 27666809 TI - Peripheral Precocious Puberty due to Functioning Adrenocortical Tumor: Description of Two Cases. AB - BACKGROUND: Adrenocortical tumors (ACTs) represent less than 0.2% of all childhood neoplasms. Frequent clinical manifestations are virilization, hypercortisolism, and peripheral precocious puberty (PPP). CASES: We describe two cases in which ACTs were responsible for virilization (case 1) and PPP (case 2) in prepubertal girls. In both cases an ACT diagnosis was made after 5-6 months from the first appearance of clinical signs. Surgery was performed within 1 month of diagnosis, and the benign nature of tumors was histologically confirmed. Despite complete tumor resection, virilizing features persisted. SUMMARY AND CONCLUSIONS: Adrenocortical tumors should be considered early in the assessment of PPP. There is often a significant delay between the onset of symptoms and accurate diagnosis but early treatment is essential to limit the clinical manifestations of androgen overproduction. PMID- 27666810 TI - Endothelial Antioxidant-1: a Key Mediator of Copper-dependent Wound Healing in vivo. AB - Copper (Cu), an essential nutrient, promotes wound healing, however, target of Cu action and underlying mechanisms remain elusive. Cu chaperone Antioxidant-1 (Atox1) in the cytosol supplies Cu to the secretory enzymes such as lysyl oxidase (LOX), while Atox1 in the nucleus functions as a Cu-dependent transcription factor. Using mouse cutaneous wound healing model, here we show that Cu content (by X-ray Fluorescence Microscopy) and nuclear Atox1 are increased after wounding, and that wound healing with and without Cu treatment is impaired in Atox1-/- mice. Endothelial cell (EC)-specific Atox1-/- mice and gene transfer of nuclear-target Atox1 in Atox1-/- mice reveal that Atox1 in ECs as well as transcription factor function of Atox1 are required for wound healing. Mechanistically, Atox1-/- mice show reduced Atox1 target proteins such as p47phox NADPH oxidase and cyclin D1 as well as extracellular matrix Cu enzyme LOX activity in wound tissues. This in turn results in reducing O2- production in ECs, NFkB activity, cell proliferation and collagen formation, thereby inhibiting angiogenesis, macrophage recruitment and extracellular matrix maturation. Our findings suggest that Cu-dependent transcription factor/Cu chaperone Atox1 in ECs plays an important role to sense Cu to accelerate wound angiogenesis and healing. PMID- 27666811 TI - Dysregulated innate immune function in the aetiopathogenesis of idiopathic inflammatory myopathies. AB - The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic muscle conditions that are believed to be autoimmune in nature. They have distinct pathological features, but the aetiopathogenesis of each subtype remains largely unknown. Recently, there has been increased interest in the complex role the innate immune system plays in initiating and perpetuating these conditions, and how this may differ between subtypes. This article summarises the traditional paradigms of IIM pathogenesis and reviews the accumulating evidence for disturbances in innate immune processes in these rare, but debilitating chronic conditions. PMID- 27666812 TI - Fecal calprotectin in systemic sclerosis: Light and shade of a promising tool. PMID- 27666813 TI - Mercury as an environmental stimulus in the development of autoimmunity - A systematic review. AB - Autoimmune diseases result from an interplay of genetic predisposition and factors which stimulate the onset of disease. Mercury (Hg), a well-established toxicant, is an environmental factor reported to be linked with autoimmunity. Hg exists in several chemical forms and is encountered by humans in dental amalgams, certain vaccines, occupational exposure, atmospheric pollution and seafood. Several studies have investigated the effect of the various forms of Hg, including elemental (Hg0), inorganic (iHg) and organic mercury (oHg) and their association with autoimmunity. In vitro studies using peripheral blood mononuclear cells (PBMC) from healthy participants have shown that methylmercury (MeHg) causes cell death at lower concentrations than iHg albeit exposure to iHg results in a more enhanced pro-inflammatory profile in comparison to MeHg. In vivo research utilising murine models susceptible to the development of metal induced autoimmunity report that exposure to iHg results in a lupus-like syndrome, whilst mice exposed to MeHg develop autoimmunity without the formation of immune complexes. Furthermore, lower concentrations of IgE are detected in MeHg-treated animals in comparison with those treated with iHg. It appears that, oHg has a negative impact on animal models with existing autoimmunity. The research conducted on humans in this area is diverse in study design and the results are conflicting. There is currently no evidence to implicate a role for Hg0 exposure from dental amalgams in the development or perpetuation of autoimmune disease, apart from some suggestion of individual sensitivity. Several studies have consistently shown a positive correlation between iHg exposure and serum autoantibody concentrations in gold miners, although the clinical impact of iHg remains unknown. Furthermore, a limited number of studies have reported individuals with autoimmune disease have higher concentrations of blood Hg compared to healthy controls. In summary, it appears that iHg perpetuates markers of autoimmunity to a greater extent than oHg, albeit the impact on clinical outcomes in humans is yet to be elucidated. PMID- 27666814 TI - Accreditation in autoimmune diagnostic laboratories. A position paper of the European Autoimmunity Standardisation Initiative (EASI). AB - Reliable autoantibody detection is important for early diagnosis and appropriate treatment of autoimmune disorders. However, in contrast to testing for classical clinical chemistry analytes, autoantibody testing is complex and evolving. Moreover, there is a lack of standardization. Nevertheless, it is important that laboratories that provide autoimmune tests comply with the requirements set forward by general international accreditation bodies. In the present manuscript, an ad hoc committee of the European Autoimmunity Standardisation Initiative (EASI) group provides background information on accreditation and identifies the minimum requirements needed to set up an accredited autoimmunity lab and to ensure that high-quality results are provided (in terms of personnel, procedures, validation, quality control, and reporting). Areas in which additional work needs to be done are identified. PMID- 27666815 TI - Role of galectin-3 in autoimmune and non-autoimmune nephropathies. AB - Galectins are evolutionary conserved beta-galactoside binding proteins with a carbohydrate-recognition domain (CRD) of approximately 130 amino acids. In mammals, 15 members of the galectin family have been identified and classified into three subtypes according to CRD organization: prototype, tandem repeat-type and chimera-type galectins. Galectin-3 (gal-3) is the only chimera type galectin in vertebrates containing one CRD linked to an unusual long N-terminal domain which displays non-lectin dependent activities. Although recent studies revealed unique, pleiotropic and context-dependent functions of gal-3 in both extracellular and intracellular space, gal-3 specific pathways and its ligands have not been clearly defined yet. In the kidney gal-3 is involved in later stages of nephrogenesis as well as in renal cell cancer. However, gal-3 has recently been associated with lupus glomerulonephritis, with Familial Mediterranean Fever-induced proteinuria and renal amyloidosis. Gal-3 has been studied in experimental acute kidney damage and in the subsequent regeneration phase as well as in several models of chronic kidney disease, including nephropathies induced by aging, ischemia, hypertension, diabetes, hyperlipidemia, unilateral ureteral obstruction and chronic allograft injury. Because of the pivotal role of gal-3 in the modulation of immune system, wound repair, fibrosis and tumorigenesis, it is not surprising that gal-3 can be an intriguing prognostic biomarker as well as a promising therapeutic target in a great variety of diseases, including chronic kidney disease, chronic heart failure and cardio renal syndrome. This review summarizes the functions of gal-3 in kidney pathophysiology focusing on the reported role of gal-3 in autoimmune diseases. PMID- 27666816 TI - Guillain-Barre syndrome. AB - The term Guillain-Barre syndrome (GBS), the most frequent cause of acute paralytic neuropathy, covers a number of recognisably distinct variants. The exact cause of GBS is unknown, but 50-70% of cases appear 1-2weeks after a respiratory or gastrointestinal infection, or another immune stimulus that induces an aberrant autoimmune response targeting peripheral nerves and their spinal roots. The interplay between the microbial and host factors that dictate whether and how the immune response shifts towards autoreactivity is still unclear, and nothing is known about the genetic and environmental factors that affect an individual's susceptibility to the disease. All patients with GBS need meticulous monitoring, and can benefit from supportive care and the early start of specific treatment. This review summarises the clinical features and diagnostic criteria of GBS and proposes an algorithm for its management. An analysis of the literature showed that, about one century after it was first described, new information concerning its etiopathogenesis has allowed the development of new treatment strategies that should be started immediately after diagnosis; however, the available therapies are not sufficient in many patients, especially in the presence of the acute inflammatory demyelinating polyneuropathy. New post-infectious forms, such as those caused by Zika virus and enterovirus D68, need to be carefully analysed and, in order to improve patient outcomes, research should continue to aim at identifying new biomarkers of disease severity and better means of avoiding axonal injury. PMID- 27666817 TI - Interstitial lung disease in systemic sclerosis patients may benefit more from anti-reflux therapies than from immunosuppressants. PMID- 27666818 TI - The clinical relevance of complex regional pain syndrome type I: The Emperor's New Clothes. AB - The management of patients with chronic pain is a nearly daily challenge to rheumatologists, neurologists, orthopedic surgeons, pain specialists and indeed a issue in nearly every clinical practice. Among the myriad of causes of pain are often included a unique syndrome, generally referred to as complex regional pain syndrome type I (CRPS). Unfortunately CRPS I has become a catch all phase and there are serious questions on whether it exists at all; this has led to an extraordinary number of poorly defined diagnostic criteria. It has also led to an etiologic quagmire that includes features as diverse as autoimmunity to simple trauma. These, in turn, have led to overdiagnosis and often overzealous use of pain medications, including narcotics. In a previous paper, we raised the issue of whether CRPS type I reflected a valid diagnosis. Indeed, the diagnostic criteria for CRPS I, and therefore the diagnosis itself, is unreliable for a number of reasons: 1) the underlying pathophysiology of the signs and symptoms of CPRS I are not biologically plausible; 2) there are no consistent laboratory or imaging testing available; 3) the signs and symptoms fluctuate over time without a medical explanation; 4) the definitions of most studies are derived from statistical analysis with little consideration to required sample size, i.e. power calculations; 5) interobserver reliability in the assessment of the signs and symptoms are often only fair to moderate, and agreement on the diagnosis of "CRPS I" is poor. Even physicians who still believe in the concept of "CRPS I" admit that it is vastly overdiagnosed and has become a diagnosis of last resort, often without a complete differential diagnosis and an alternative explanation. Finally, one of the most convincing arguments that there is no clinical entity as "CRPS I" comes from the enormous heterogeneity in sign and symptom profiles and the heterogeneity of pathophysiological mechanisms postulated. This observation is underscored by the diversity of responses among "CRPS I" patients to essentially all treatment modalities. It has even led to the concept that the signs and symptoms of CRPS can spread throughout the body, as if it is an infectious disease, without any medical plausible explanation. If true progress is to be made in helping patients with pain, it will require entirely new and different concepts and abandoning CRPS I as a legitimate diagnosis. PMID- 27666819 TI - Are psoriasis and psoriatic arthritis the same disease? The IL-23/IL-17 axis data. AB - Psoriatic arthritis (PsA) is a psoriasis (Ps)-associated inflammatory joint disease that affects peripheral joints, entheses, spine, and eyes. PsA and Ps are likely to be the same disease. PsA develops in nearly 70% of patients with Ps, and the hallmark of the disease is bone erosions and bone formation. Both innate and adaptive immunity appear to contribute to pathogenesis of PsA and Ps. Trauma may be a trigger factor for both PsA and Ps. The same T cell clones were reported to be present in both synovial tissues and skin lesions suggesting that a common antigen drives T cell immune response in the joints and skin lesions of patients with PsA. The IL-23/IL-17 axis plays a critical pathogenic role for both PsA and Ps, and biologics neutralizing IL-17A or IL-23/IL-12 are effective therapies for PsA and Ps. The differential expression of Th17 cytokines IL-17 and IL-22 at various sites could explain the different manifestations of the disease. IL-17 is highly expressed in peripheral joints and skin lesions and causes bone erosions. IL-22 is highly expressed in skin lesions and entheses, not peripheral joints, and cause bone formation. Finally, mannan from baker's yeast caused PsA-like arthritis and Ps-like skin lesions that were blocked by IL-17 treatment. These data suggest that PsA and Ps are likely to be the same disease exhibiting different manifestations depending on the local cytokine production. PMID- 27666820 TI - Long non-coding RNAs regulate effects of beta-crystallin B2 on mouse ovary development. AB - beta-crystallin B2 (CRYBB2) knockout mice exhibit morphological and functional abnormalities in the ovary. Long non-coding RNAs (lncRNAs) regulate gene transcription and translation, and epigenetic modification of genomic DNA. The present study investigated the role of lncRNAs in mediating the effects of CRYBB2 in the regulation of ovary development in mice. In the current study, ovary tissues from wild-type (WT) and CRYBB2 knockout mice were subjected to lncRNA and mRNA microarray profiling. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to group the differentially expressed lncRNAs into regulated gene pathways and functions. The correlation matrix method was used to establish a network of lncRNA and mRNA co-expression. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify expression of a number of these differentially expressed lncRNAs and mRNAs. There were 157 differentially expressed lncRNAs and 1,085 differentially expressed mRNAs between ovary tissues from WT and CRYBB2 knockout mice. The GO and KEGG analyses indicated that these differentially expressed lncRNAs and mRNAs were important in Ca2+ signaling and ligand and receptor interactions. The correlation matrix method established an lncRNA and mRNA co-expression network, consisting of 53 lncRNAs and 45 mRNAs with 98 nodes and 75 connections. RT-qPCR confirmed downregulation of lncRNA A-30-P01019163 expression, which further downregulated its downstream gene purinergic receptor P2X, ligand-gated ion channel, 7 (P2rx7) expression in ovary tissues from CRYBB2 knockout mice. In conclusion, CRYBB2 regulates expression of different lncRNAs to influence ovary development. lncRNA A-30-P01019163 may affect ovarian cell cycle and proliferation by regulating P2rx7 expression in the ovary. PMID- 27666821 TI - The tobacco-specific carcinogen-operated calcium channel promotes lung tumorigenesis via IGF2 exocytosis in lung epithelial cells. AB - Nicotinic acetylcholine receptors (nAChRs) binding to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces Ca2+ signalling, a mechanism that is implicated in various human cancers. In this study, we investigated the role of NNK-mediated Ca2+ signalling in lung cancer formation. We show significant overexpression of insulin-like growth factors (IGFs) in association with IGF-1R activation in human preneoplastic lung lesions in smokers. NNK induces voltage-dependent calcium channel (VDCC)-intervened calcium influx in airway epithelial cells, resulting in a rapid IGF2 secretion via the regulated pathway and thus IGF-1R activation. Silencing nAChR, alpha1 subunit of L-type VDCC, or various vesicular trafficking curators, including synaptotagmins and Rabs, or blockade of nAChR/VDCC-mediated Ca2+ influx significantly suppresses NNK-induced IGF2 exocytosis, transformation and tumorigenesis of lung epithelial cells. Publicly available database reveals inverse correlation between use of calcium channel blockers and lung cancer diagnosis. Our data indicate that NNK disrupts the regulated pathway of IGF2 exocytosis and promotes lung tumorigenesis. PMID- 27666824 TI - Does a person selectively recall the good or the bad from their personal past? It depends on the recall target and the person's favourability of self-views. AB - In three studies, participants remembered real-life behaviours at Time 1 and attempted to recall them at Time 2. When the recall target was the self, a positivity bias emerged: self-positivity. In Study 3, self-positivity extended to an individual (target) who was liked by the participant, but did it not extend to a disliked target. For this latter target, a negativity bias emerged. For recall targets that were participants' acquaintances, self-positivity in recall was also eliminated in Studies 1 and 3, and a negativity bias in recall emerged in Study 2. Finally, in Study 2 (but not Study 3), the favourability of participants' self view predicted the magnitude of the self-positivity in self-recall, but it did not predict valence effects in other-recall. Taken together, the results indicate that the link between behaviour valence and recall is moderated by the recall target and the favourability of one's self-view. PMID- 27666823 TI - Cerebral ischemic post-conditioning induces autophagy inhibition and a HMGB1 secretion attenuation feedback loop to protect against ischemia reperfusion injury in an oxygen glucose deprivation cellular model. AB - Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment. Transmission electron microscopy was performed to observe the formation of autophagosomes, and immunofluorescence, western blot and co immunoprecipitation were used to examine the expression of autophagy-associated proteins and HMGB1. Enzyme-linked immunosorbent assay analysis was conducted to examine the level of HMGB1 in cell supernatants. Additionally, PC12 cells were treated with RAP to examine the effect of autophagy on HMGB1 release, and the effect of recombinant human HMGB1 and Beclin1 small interfering RNA on autophagy was investigated. The present study confirmed that IPOC inhibited autophagy and HMGB1 secretion, autophagy inhibition induced a decrease in HMGB1 secretion, and HMGB1 secretion attenuation caused autophagy inhibition in return, as demonstrated by immunofluorescence and western blot analyses. Autophagy inhibition and HMGB1 secretion attenuation were, therefore, demonstrated to form a feedback loop under IPOC. These mechanisms illustrated the protective effects of IPOC and may accelerate the clinical use of IPOC. PMID- 27666822 TI - Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome. AB - Short-rib polydactyly syndromes (SRPS) and Asphyxiating thoracic dystrophy (ATD) or Jeune Syndrome are recessively inherited skeletal ciliopathies characterized by profound skeletal abnormalities and are frequently associated with polydactyly and multiorgan system involvement. SRPS are produced by mutations in genes that participate in the formation and function of primary cilia and usually result from disruption of retrograde intraflagellar (IFT) transport of the cilium. Herein we describe a new spectrum of SRPS caused by mutations in the gene IFT81, a key component of the IFT-B complex essential for anterograde transport. In mutant chondrocytes, the mutations led to low levels of IFT81 and mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components. These findings demonstrate the importance of IFT81 in the skeleton, its role in the anterograde transport complex, and expand the number of loci associated with SRPS. PMID- 27666827 TI - Letter to the Editor in response to: Important knowledge for parents of children with heart disease: parent, nurse, and physician views. PMID- 27666825 TI - MuSK Kinase Activity is Modulated By A Serine Phosphorylation Site in The Kinase Loop. AB - The neuromuscular junction (NMJ) forms when a motor neuron contacts a muscle fibre. A reciprocal exchange of signals initiates a cascade of signalling events that result in pre- and postsynaptic differentiation. At the centre of these signalling events stands muscle specific kinase (MuSK). MuSK activation, kinase activity and subsequent downstream signalling are crucial for NMJ formation as well as maintenance. Therefore MuSK kinase activity is tightly regulated to ensure proper NMJ development. We have identified a novel serine phosphorylation site at position 751 in MuSK that is increasingly phosphorylated upon agrin stimulation. S751 is also phosphorylated in muscle tissue and its phosphorylation depends on MuSK kinase activity. A phosphomimetic mutant of S751 increases MuSK kinase activity in response to non-saturating agrin concentrations . In addition, basal MuSK and AChR phosphorylation as well as AChR cluster size are increased. We believe that the phosphorylation of S751 provides a novel mechanism to relief the autoinhibition of the MuSK activation loop. Such a lower autoinhibition could foster or stabilize MuSK kinase activation, especially during stages when no or low level of agrin are present. Phosphorylation of S751 might therefore represent a novel mechanism to modulate MuSK kinase activity during prepatterning or NMJ maintenance. PMID- 27666828 TI - Anaerobic digestion of grass: the effect of temperature applied during the storage of substrate on the methane production. AB - Within this research, biogas production, representation of methane in biogas and volatile solids (VSs) removal efficiency were compared using batch tests performed with the samples of intensively and extensively planted grasses originating from public areas. Before the batch tests, the samples were stored at different temperatures achievable on biogas plants applying trigeneration strategy (-18 degrees C, +3 degrees C, +18 degrees C and +35 degrees C). Specific methane production from intensively planted grasses was relatively high (0.33 0.41 m3/kg VS) compared to extensively planted grasses (0.20-0.33 m3/kg VS). VSs removal efficiency reached 59.8-68.8% for intensively planted grasses and 34.6 56.5% for extensively planted grasses. Freezing the intensively planted grasses at -18 degrees C proved to be an effective thermal pretreatment leading to high biogas production (0.61 m3/kg total solid (TS)), high representation of methane (64.0%) in biogas and good VSs removal efficiency (68.8%). The results of this research suggest that public areas or sport parks seem to be available, cheap and at the same time very effective feedstock for biogas production. PMID- 27666826 TI - Systemic blockade of ACVR2B ligands prevents chemotherapy-induced muscle wasting by restoring muscle protein synthesis without affecting oxidative capacity or atrogenes. AB - Doxorubicin is a widely used and effective chemotherapy drug. However, cardiac and skeletal muscle toxicity of doxorubicin limits its use. Inhibiting myostatin/activin signalling can prevent muscle atrophy, but its effects in chemotherapy-induced muscle wasting are unknown. In the present study we investigated the effects of doxorubicin administration alone or combined with activin receptor ligand pathway blockade by soluble activin receptor IIB (sACVR2B Fc). Doxorubicin administration decreased body mass, muscle size and bone mineral density/content in mice. However, these effects were prevented by sACVR2B-Fc administration. Unlike in many other wasting situations, doxorubicin induced muscle atrophy without markedly increasing typical atrogenes or protein degradation pathways. Instead, doxorubicin decreased muscle protein synthesis which was completely restored by sACVR2B-Fc. Doxorubicin administration also resulted in impaired running performance without effects on skeletal muscle mitochondrial capacity/function or capillary density. Running performance and mitochondrial function were unaltered by sACVR2B-Fc administration. Tumour experiment using Lewis lung carcinoma cells demonstrated that sACVR2B-Fc decreased the cachectic effects of chemotherapy without affecting tumour growth. These results demonstrate that blocking ACVR2B signalling may be a promising strategy to counteract chemotherapy-induced muscle wasting without damage to skeletal muscle oxidative capacity or cancer treatment. PMID- 27666829 TI - RbTiOPO4 cascaded Raman operation with multiple Raman frequency shifts derived by Q-switched Nd:YAlO3 laser. AB - An intra-cavity RbTiOPO4 (RTP) cascade Raman laser was demonstrated for efficient multi-order Stokes emission. An acousto-optic Q-switched Nd:YAlO3 laser at 1.08 MUm was used as the pump source and a 20-mm-long x-cut RTP crystal was used as the Raman medium to meet the X(Z,Z)X Raman configuration. Multi-order Stokes with multiple Raman shifts (~271, ~559 and ~687 cm-1) were achieved in the output. Under an incident pump power of 9.5 W, a total average output power of 580 mW with a pulse repetition frequency of 10 kHz was obtained. The optical conversion efficiency is 6.1%. The results show that the RTP crystal can enrich laser spectral lines and generate high order Stokes light. PMID- 27666831 TI - Nursing organisations 'saddened' by conflict. AB - As hostilities began, nurses' organisations expressed concern for colleagues and others involved in the war. PMID- 27666832 TI - ? AB - Eleventh-hour peace plea: Health Visitors' Association General Secretary Catherine Burns, right, joined other health visitors and nurses in protesting for peace at Trafalgar Square just before the United Nations' deadline expired. PMID- 27666830 TI - Mine is not to reason why? AB - An air of tension gripped the country as Nursing Standard went to press. As the full realisation of war unfolded on our television screens, no one could predict where it would end. Secrecy surrounded the number of wounded and reports of pilots and navigators lost in action brought home to us the human cost of warfare. PMID- 27666833 TI - NHS prepares for casualties. AB - Nurses preparing for a flood of Gulf War casualties in hospitals throughout Britain were described as 'tense' but well- prepared last week, as Allied troops attacked Iraq. PMID- 27666834 TI - Early Day Motion calls for 'attractive' salaries. AB - All-party support for a substantial pay rise for nurses is growing as unions await publication of this year's report from the Review Body on pay. PMID- 27666835 TI - Cleared nurse may not be offered her job back. AB - A health authority chief said last week that enrolled nurse Florence McKenley, who was cleared of manslaughter at the Old Bailey, would 'not necessarily' be offered her job back. PMID- 27666836 TI - ? AB - Peace pledge: Marjorie Thompson, Chair of the Campaign for Nuclear Disarmament and RCN Parliamentary Officer, took centre stage in Trafalgar Square at last week's mass rally against the Gulf war, just a few days before fighting began. PMID- 27666837 TI - Waldergrave signals go-slow on NHS reforms. AB - Health Secretary William Waldegrave last week declared an NHS reform slowdown, to the frustration of front-line Trust managers. PMID- 27666838 TI - RCN council. AB - Senior nurses have been warned that they could face charges of malicious behaviour if they 'blacklist' colleagues. PMID- 27666839 TI - ? AB - RCN President Professor June Clark took the opportunity to underline the importance of nurse education at last week's College annual dinner where Health Secretary William Waldegrave delivered the after-dinner speech. PMID- 27666840 TI - GPs reject independence for practice nurses. AB - Family doctors remain overwhelmingly opposed to the idea of independent nurse practitioners, a new study shows. PMID- 27666841 TI - Commons row blocks health committee. AB - The creation of the Commons' new streamlined Select Committee on Health has been blocked in a row over the Government's refusal to re-appoint a Scottish select committee. PMID- 27666842 TI - Care workers told to give more freedom to elderly. AB - Health care workers must change their overprotective approach to dealing with older people, a new report urges. PMID- 27666844 TI - Summit calls for shared post-registration training. AB - Primary health care nursing is expected to become the generic term for all nurses working in the community if proposals made at a secret summit meeting are accepted by the United Kingdom Central Council. PMID- 27666843 TI - Employers 'fail to understand' injury law. AB - Regulations relating to employees' risks of sustaining injury at work have been 'fragmented and ineffective', with employers failing to understand what the law requires, according to Richard Sharpe of the Health and Safety Executive. PMID- 27666846 TI - Parliament. AB - Welsh health managers have been told to start taking tough 'value-for-money' decisions over which cancer patients can undergo surgery. PMID- 27666849 TI - World news. AB - United States The Royal College of Nursing has moved to allay fears that British nurses might be deported from the United States under new regulations on working visas introduced last September. PMID- 27666851 TI - Danger of X-rays without checks. AB - Nearly 30 per cent of women of childbearing age X-rayed between the ribs and the knees say that no attempt was made to find out if they were pregnant before the X ray was taken, according to a recent survey. PMID- 27666850 TI - ? AB - Third World Housework in the poorer developing countries poses a serious health risk to women, a new report on women's lives reveals. PMID- 27666853 TI - Booklet launched on Tuberous Sclerosis. AB - Over 5,000 people in the UK are affected by Tuberous Sclerosis (TS), an incurable condition with varying symptoms including mental retardation and epilepsy. PMID- 27666852 TI - Caution urged over HIV drug licensed in kenya. AB - The Canadian government is to back the trial of a controversial new drug which Kenyan researchers have claimed can halt the spread of HIV, according to a report in New Scientist magazine. PMID- 27666855 TI - Pregnancy fears over gases. AB - The Royal College of Nursing is concerned about the effect of waste anaesthetic gases (WAG), such as nitrous oxide, halothane and isoflurane, on the reproductive system. PMID- 27666854 TI - Preventing the majority of asthma deaths. AB - The majority of the 2,000 deaths in the UK each year from asthma are preventable and occur mainly because of an over-reliance on first aid for symptoms rather than regular treatment. PMID- 27666856 TI - Don't forget your post code. AB - While doing agency nursing at a Norfolk hospital, I read a memo from the X-ray Department stating that 'no X-rays would be be carried out on patients whose X ray forms did not state their post code'. PMID- 27666857 TI - Information exchange. AB - The Royal College of Nursing Association of Nursing Education provides an ideal forum for developing and co-ordinating a supportive network to facilitate sharing of experiences about the implementation of Project 2000. PMID- 27666859 TI - No 'automatic conversion'. AB - I am writing to dispel the apparent nursing myth that it is a foregone conclusion that SENs automatically pass their conversion courses. PMID- 27666858 TI - Smear test incompetence? AB - I am 55, single and celibate, and have never had a cervical smear test as I thought it unnecessary, until I received a request to have it done at my doctor's surgery. PMID- 27666860 TI - The right organisation. AB - Re: Susan Dukes' 'Establishing a bereavement service' (Nursing Standard November 28 1990). PMID- 27666862 TI - Discharge Planning Guide for Nurses Discharge Planning Guide for Nurses Roivden J and Saunders E Taft 384pp L17.95 0-7216-2845-1 [Formula: see text]. AB - Discharge Planning Guide for Nurses is a valuable addition to any nursing library. PMID- 27666861 TI - Shiftless mothers? AB - Nursing is uniquely suited to job-sharing. Unlike any other professional, the nurse has always handed over to another nurse at the end of their shift. No nurse works in isolation and team work and handovers are an intrinsic part of nursing. PMID- 27666863 TI - Leadership, 2nd edition Leadership, 2nd edition Bernhard L , Walsh M Como N Mosby 228pp L17.95 0-8016-60661-1 [Formula: see text]. AB - Change is likely to be the one consistent factor facing health-service personnel over the next few years. Such change will require careful planning, an emphasis on clarity of objectives and an ability to co-ordinate activity across the many levels and divisions, both within the organisation and between the various other agencies which may have a stake in the outcome. PMID- 27666864 TI - Case Studies in Cardiovascular Critical Care Nursing Case Studies in Cardiovascular Critical Care Nursing M Walsh J Clochesy Aspen 292pp L40.00 0-8342 0115-1 [Formula: see text]. AB - Mickie Walsh and John Clochesy aim to show how the use of two conceptual models of nursing can guide nursing practice in the critical care setting. PMID- 27666866 TI - Mitral valvuloplasty: the Inoue technique. AB - The first mitral valvuloplasty was carried out in Japan some five years ago and introduced into this country shortly afterwards. Normally, patients with mitral valve disease whose symptoms are not controlled by medical therapy are offered surgery, which has a mortality rate of some 7-10 per cent. PMID- 27666865 TI - Health and wealth. AB - The Association of Community Health Councils has launched a health news briefing document titled 'Health and wealth - a review of health inequalities in the UK' ( 1 ). The document states that the evidence linking ill health and mortality with poverty is overwhelming. PMID- 27666867 TI - Nb2O5-gamma-Al2O3 nanofibers as heterogeneous catalysts for efficient conversion of glucose to 5-hydroxymethylfurfural. AB - One-dimensional gamma-Al2O3 nanofibers were modified with Nb2O5 to be used as an efficient heterogeneous catalyst to catalyze biomass into 5-hydroxymethylfurfural (5-HMF). At low Nb2O5 loading, the niobia species were well dispersed on gamma Al2O3 nanofiber through Nb-O-Al bridge bonds. The interaction between Nb2O5 precursor and gamma-Al2O3 nanofiber results in the niobia species with strong Lewis acid sites and intensive Bronsted acid sites, which made 5-HMF yield from glucose to reach the maximum 55.9~59.0% over Nb2O5-gamma-Al2O3 nanofiber with a loading of 0.5~1 wt% Nb2O5 at 150 degrees C for 4 h in dimethyl sulfoxide. However, increasing Nb2O5 loading could lead to the formation of two-dimensional polymerized niobia species, three-dimensional polymerized niobia species and crystallization, which significantly influenced the distribution and quantity of the Lewis acid sites and Bronst acid sites over Nb2O5-gamma-Al2O3 nanofiber. Lewis acid site Nbdelta+ played a key role on the isomerization of glucose to fructose, while Bronsted acid sites are more active for the dehydration of generated fructose to 5-HMF. In addition, the heterogeneous Nb2O5-gamma-Al2O3 nanofiber catalyst with suitable ratio of Lewis acid to Bronsted sites should display an more excellent catalytic performance in the conversion of glucose to 5 HMF. PMID- 27666868 TI - Gender effects of single nucleotide polymorphisms and miRNAs targeting clock genes in metastatic colorectal cancer patients (mCRC). AB - The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR 132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months. This difference was associated with rs11133373 C/C genotype (p = 0.01), rs1801260 T/C+C/C genotype (p = 0.06) and rs11133391 T/T genotype (p = 0.06). Moreover women expressing high levels (H) of miR-192 (p = 0.03), miR-206 (p = 0.003), miR-194 (p = 0.02) and miR 219 (p = 0.002) had a longer OS compared to men. In women longer OS was reinforced by the simultaneous presence of two or more H-miR, 58 months versus 15 months (p = 0.0008); in this group of women an OS of 87 months was reached with the additional presence of rs11133391T/T genotype (p = 0.02). In this study we identified a subgroup of female patients who seems to have a better prognosis. Personalized medicine should prospectively take into account both genetic and gender differences. PMID- 27666869 TI - Controllable Edge Oxidation and Bubbling Exfoliation Enable the Fabrication of High Quality Water Dispersible Graphene. AB - Despite significant progresses made on mass production of chemically exfoliated graphene, the quality, cost and environmental friendliness remain major challenges for its market penetration. Here, we present a fast and green exfoliation strategy for large scale production of high quality water dispersible few layer graphene through a controllable edge oxidation and localized gas bubbling process. Mild edge oxidation guarantees that the pristine sp2 lattice is largely intact and the edges are functionalized with hydrophilic groups, giving rise to high conductivity and good water dispersibility at the same time. The aqueous concentration can be as high as 5.0 mg mL-1, which is an order of magnitude higher than previously reports. The water soluble graphene can be directly spray-coated on various substrates, and the back-gated field effect transistor give hole and electron mobility of ~496 and ~676 cm2 V-1 s-1, respectively. These results achieved are expected to expedite various applications of graphene. PMID- 27666870 TI - Effects of thyroid hormone withdrawal on natriuretic peptides during radioactive iodine therapy in female patients with differentiated thyroid cancer. AB - OBJECTIVE: We aimed to investigate the effects of thyroid hormone withdrawal on N terminal prohormone forms of atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (NT-proBNP) during radioiodine therapy in female patients with differentiated thyroid cancer (DTC). METHODS: Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), NT-proANP and NT proBNP were measured in 51 female patients with DTC (48.7 +/- 4.2 years) at three time-points: day of radioiodine therapy (t1 - under acute hypothyroidism), 5 days after radioiodine (t2 - under acute hypothyroidism) and 3 months after radioiodine (t3 - under TSH suppression). Thirty healthy euthyroid women served as controls (42.8 +/- 5.6 years). RESULTS: At t1/t2/t3, median NT-proANP was 5.2/1.7/487 pmol/L vs. 297.7 pmol/L in control group (p < 0.001), median NT proBNP was 50.1/36.5/79.5 pmol/L vs. 64.5 pmol/L (p < 0.001) and median NT proANP/NT-proBNP ratios was 0.20/0.18/4.81 vs. 4.14 (p < 0.001). In acute hypothyroidism, FT3 levels were positively correlated with NT-proANP (r = 0.38, p = 0.005), NT-proANP/NT-proBNP ratios (r = 0.47, p = 0.001), heart rate (r = 0.39, p = 0.005), and negatively with mean arterial blood pressure (r = -0.58, p < 0.001). CONCLUSIONS: Our results indicate that NT-proANP reflects more accurately direct thyroid hormone effects than NT-proBNP. Thyroid hormone-dependent hemodynamic effects seem to be overlapped on the direct stimulatory effect of thyroid hormones on NT-proANP secretion by cardiac myocytes. PMID- 27666871 TI - Differential expression of miR-184 in temporal lobe epilepsy patients with and without hippocampal sclerosis - Influence on microglial function. AB - Epilepsy is one of the most common neurological disorders characterized by recurrent seizures due to neuronal hyperexcitability. Here we compared miRNA expression patterns in mesial temporal lobe epilepsy with and without hippocampal sclerosis (mTLE + HS and mTLE -HS) to investigate the regulatory mechanisms differentiating both patient groups. Whole genome miRNA sequencing in surgically resected hippocampi did not reveal obvious differences in expression profiles between the two groups of patients. However, one microRNA (miR-184) was significantly dysregulated, which was confirmed by qPCR. We observed that overexpression of miR-184 inhibited cytokine release after LPS stimulation in primary microglial cells, while it did not affect the viability of murine primary neurons and primary astrocytes. Pathway analysis revealed that miR-184 is potentially involved in the regulation of inflammatory signal transduction and apoptosis. Dysregulation of some the potential miR-184 target genes was confirmed by qPCR and 3'UTR luciferase reporter assay. The reduced expression of miR-184 observed in patients with mTLE + HS together with its anti-inflammatory effects indicate that miR-184 might be involved in the modulation of inflammatory processes associated with hippocampal sclerosis which warrants further studies elucidating the role of miR-184 in the pathophysiology of mTLE. PMID- 27666872 TI - Microbial transformation of hederagenin by Cunninghamella echinulate, Mucor subtilissimus, and Pseudomonas oleovorans. AB - The pentacyclic triterpenoid hederagenin (1) was subjected to biotransformation by Cunninghamella echinulate CGMCC 3.2000, Mucor subtilissimus CGMCC 3.2454 and Pseudomonas oleovorans CGMCC 1.1641. Three metabolites were obtained. On the basis of nuclear magnetic resonance and high-resolution mass spectral analyses, their structures were characterized as 3beta, 23-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester (2), 3beta, 15alpha, 23-trihydroxyolean-12-en-28 oic acid (3), 1beta, 3beta, 23-trihydroxyolean-12-en-28-oic acid (4), and metabolite (3) was a new compound. This was the first report on the biotransformation of hederagenin. PMID- 27666873 TI - Enhancement of the topical tolnaftate delivery for the treatment of tinea pedis via provesicular gel systems. AB - Tolnaftate is a thiocarbamate antifungal drug which is therapeutically active against dermatophytes that cause various forms of tinea. Due to the small amount of tolnaftate released from ordinary ointment bases and insufficient penetration through the infected skin layers the need to incorporate the drug in a more suitable pharmaceutical form has evolved. A provesicular system is one such form that can solve these problems. Once in contact with the skin, dilution with moisture occurs and the provesicular system rapidly transforms into a vesicular one. Provesicular systems were prepared according to full-factorial experimental design. Plain provesicular systems were compared with systems containing Phospholipon 80 H and Lipoid S45 as penetration enhancers. Design expert software was used to analyze the effect of formulation variables (type of Span used as well as the presence or the absence of the penetration enhancer and its type) on the dependent variables: percent encapsulation efficiency (EE%), vesicle size and percent in vitro drug released). Three formulations were chosen; a plain provesicular system (PV-2), one containing Phospholipon 80H (PV-6) and another containing Lipoid S45 (PV-10) with the goal to reveal the effect of penetration enhancer on morphology, rheological properties and ex vivo permeation using confocal laser scanning microscopy (CLSM). Analysis of CLSM results showed that the penetration enhancing effect for the tested formulations followed the order PV-10 > PV-6 > PV-2. Promising clinically active treatment for tinea patients could be expected as shown by the in vivo permeation results for the provesicular systems as suggested by the CLSM results. PMID- 27666874 TI - Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/beta-catenin pathway in hepatocellular carcinoma cells. AB - Hypoxia-induced epithelial-to-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) was investigated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a positive regulator of the Wnt/beta-catenin signaling pathway and is overexpressed in many human tumors. However, the expression and role of FRAT1 in HCC has not been elucidated. In this study, we investigated the effect of FRAT1 on EMT process in HCC cells induced by hypoxia. Our results showed that FRAT1 is highly expressed in HCC tissues and cell lines. Hypoxia significantly induced FRAT1 expression in HCC cells. FRAT1 knockdown inhibited hypoxia-induced cell migration/invasion, downregulation of epithelial markers and upregulation of mesenchymal markers. Moreover, FRAT1 knockdown suppressed the expression levels of beta-catenin, cyclin D1 and c-myc in HCC cells under the same hypoxic condition. Our results revealed that FRAT1 is a hypoxia factor that is critical for the induction of EMT in HCC cells. These data suggest a potential role for targeting FRAT1 in the prevention of hypoxia-induced HCC cancer progression and metastasis mediated by EMT. PMID- 27666875 TI - Ferroelectricity by Bose-Einstein condensation in a quantum magnet. AB - The Bose-Einstein condensation is a fascinating phenomenon, which results from quantum statistics for identical particles with an integer spin. Surprising properties, such as superfluidity, vortex quantization or Josephson effect, appear owing to the macroscopic quantum coherence, which spontaneously develops in Bose-Einstein condensates. Realization of Bose-Einstein condensation is not restricted in fluids like liquid helium, a superconducting phase of paired electrons in a metal and laser-cooled dilute alkali atoms. Bosonic quasi particles like exciton-polariton and magnon in solids-state systems can also undergo Bose-Einstein condensation in certain conditions. Here, we report that the quantum coherence in Bose-Einstein condensate of the magnon quasi particles yields spontaneous electric polarization in the quantum magnet TlCuCl3, leading to remarkable magnetoelectric effect. Very soft ferroelectricity is realized as a consequence of the O(2) symmetry breaking by magnon Bose-Einstein condensation. The finding of this ferroelectricity will open a new window to explore multi functionality of quantum magnets. PMID- 27666877 TI - [Primary and secondary prophylaxis of liver cirrhosis gastroesophageal varices]. PMID- 27666876 TI - Dynamics of Humic Acid and Its Interaction with Uranyl in the Presence of Hydrophobic Surface Implicated by Molecular Dynamics Simulations. AB - This work targeted a molecular level of understanding on the dynamics of humic acid (HA) and its interaction with uranyl in the presence of hydrophobic surface mimicked by a carbon nanotube (CNT), which also represents a potential intruder in the environment accompanying with the development of nanotechnology. In aqueous phase, uranyl and HA were observed to build close contact spontaneously, driven by electrostatic interaction, leading to a more compact conformation of HA. The presence of CNT unfolds HA via pi-pi interactions with the aromatic rings of HA without significant perturbation on the interaction strength between HA and uranyl. These results show that the hydrophilic uranyl and the hydrophobic CNT influence the folding behavior of HA in distinct manners, which represents two fundamental mechanisms that the folding behavior of HA may be modulated in the environment, that is, uranyl enhances the folding of HA via electrostatic interactions, whereas CNT impedes its spontaneous folding via van der Waals (vdW) interactions. The work also provides molecular level of evidence on the transformation of a hydrophobic surface into a hydrophilic one via noncovalent functionalization by HA, which in turn affects the migration of HA and the cations it binds to. PMID- 27666878 TI - [Impact of concomitant use of P2Y12 inhibitors and proton pump inhibitors on ischemia events in patients with acute coronary syndrome in real world]. AB - Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs. PMID- 27666879 TI - [Needle electromyography features and values of paraspinal muscle parameters in assessment of respiratory function of patients with amyotrophic lateral sclerosis]. AB - Objective: To analyze the features of needle electromyography (EMG) in patients with amyotrophic lateral sclerosis (ALS), and explore the correlation between EMG parameters of the tenth thoracic paraspinal muscle and disease duration, rate of disease progression, forced vital capacity (FVC) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Methods: Standard EMG was recorded from unilateral sternocleidomastoid muscle and/or tongue muscles, upper and lower limbs muscles and the tenth thoracic paraspinal muscle in 112 patients with definite ALS between March 2012 and June 2013 in the Department of Neurology at Chinese PLA General Hospital. Parameters studies included spontaneous potentials, duration and amplitude of motor unit potentials (MUP), pattern of recruitment. Results: EMG revealed diffuse neurogenic changes in each case. Fibrillation potential or positive sharp waves were found in some muscles in all of patients, and both of them were found in most of the cases. Fasciculation potentials (FPs) were found in 8 patients and accompanied with fibrillation potential and positive sharp waves in 5 of them. Complex repetitive discharges (CRDs) were found in only 1 patient. Duration and amplitude of MUP was prolonged and increased in ALS patients, and the rate of high amplitude and decreased recruitment pattern were 35.71% and 72.32%, respectively. Logistic regression analysis revealed an association of the FVC loss with the drop of ALSFRS-R and peak amplitude of the tenth thoracic paraspinal muscle. Conclusions: The abnormal spontaneous activity with high frequency are fibrillation potentials and/or positive sharp waves. However, FPs is observed in a small number of patients and CRDs is rarely seen in ALS. The ALSFRS-R and peak amplitude of thetenth thoracic paraspinal muscle may be of certain clinical value in estimating the severity of disease especially the respiratory dysfunction in ALS patients. PMID- 27666881 TI - [Spontaneous intracranial hypotension: 12 case reports and follow-up]. AB - Objective: To investigate the pathogenesis, clinical presentation, imaging features and prognosis of spontaneous intracranial hypotension. Methods: Clinical manifestation and imaging changes of 12 patients with spontaneous intracranial hypotension were reported. They were followed up regularly. The clinical and neuroimaging characteristics were summarized. Results: All the 12 cases were adults, presenting with orthostatic headache. They all recovered with conservative therapy. Head MRI demonstrated cerebral lobe hemorrhage, subdural hematoma, pituitary hyperemia, subarachnoid hemorrhage, enhancement of the pachymeninges, sagging of the brain, etc. Conclusions: Spontaneous intracranial hypotension is characterized by orthostatic headaches and is associated with compensatory changes following loss of CSF volume. The long-time prognosis is not bad. PMID- 27666880 TI - [Characteristics of sympathetic skin response in patients with multiple system atrophy]. AB - Objective: To provide evidence for early clinical diagnosis of multiple system atrophy(MSA)by studying the characteristics of sympathetic skin responses(SSR) in the patients with MSA. Methods: A total of 47 MSA patients and 32 healthy individuals were enrolled as case group and normal control(NC) group, from in and out patients of Neurology Department of Navy General Hospital from July 2013 to August 2015. SSR was tested by Nicolet electromyography, the latency and abnormal and disappeared rate of SSR were compared. Results: The SSR latency of upper limbs and lower limbs in MSA group had statistical significance compared respectively with the NCgroup (upper limbs: SSR latency was(1 485+/-187)ms in MSA group, and(1 375+/-108)ms in NC group, P<0.05; lower limbs: SSR latency was(2 200+/-386)ms in MSA group, and(1 994+/-240)ms in NC group, P<0.05). Sex and age had no significant effect on the latency and the abnormal and disappeared rate of SSR in two groups (P>0.05). The upper and lower limb SSR latency in MSA patients with disease duration more than 2 years(SSR latency was (1 592+/-160)ms in upper limb and (2 268+/-254)ms in lower limb) were longer than those within 2 years(SSR latency was (1 453+/-184)ms in upper limb and (2 190+/-442)ms in lower limb), but only the upper limbs had significantly statistical differences (P<0.05). Both SSR abnormal rate and SSR disappeared rate in MSA patients whose disease duration were more than 2 years(SSR abnormal rate: 85.00%, SSR disappeared rate: 75.00%) were higher than those with shorter disease duration(SSR abnormal rate: 55.56%, SSR disappeared rate: 22.22%), and both were statistically significant (SSR abnormal rate: P<0.05, SSR disappeared rate: P<0.001). The upper and lower limb SSR latency of MSA-C subgroup had no statistical difference compared with MSA-P subgroup(P>0.05). The SSR abnormal rate in MSA-C subgroup(78.13%) was higher than that of MSA-P subgroup(46.76%), and were statistically significant (P<0.05). The SSR disappeared rate in MSA-C subgroup has no statistical difference compared with the MSA-P subgroup(P>0.05). Conclusions: SSR is helpful to diagnose MSA. The latency and the abnormal and disappeared rate of SSR are significantly increased with the extension of MSA duration. The SSR abnormal rate in MSA-C patients is higher than that in MSA-P patients, and symmetrically abnormal SSR is more supporting the diagnosis of MSA. PMID- 27666882 TI - [Radiofrequency ablation combined with systemic chemotherapy in the management of nasopharyngeal carcinoma with liver metastasis]. AB - Objective: To determine the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (chemo-RFA) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Methods: A total of 427 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center between January 2000 and December 2013 were enrolled. Of the patients, 340 cases were male, 87 cases were female, the median age was 45 years (range 18-80 years), all patients received systemic chemotherapy and part of them also received RFA treatment. Patients were evaluated for response every two cycles during systemic chemotherapy and then every three months until death. One-to-one matched pairs between chemo-RFA group with chemo-only group were generated using propensity score matching; survival analysis was further conducted. Results: Of all the enrolled patients, 56 patients (13.1%) received combined treatment, 371 patients (86.9%)received chemotherapy alone. After propensity score matching, 56 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The 1-, 3-, 5- year overall survival (OS) rates for chemo-RFA group were 89.2%, 45.5% and 32.5% and chemo-only group were 77.1%, 27.5% and 4.8% respectively; the 1-, 3-, 5- year progression-free survival (PFS) rates for chemo RFA group were 64.0%, 25.4% and 10.7% and chemo-only group were 44.1%, 5.5% and 5.5% respectively.The adjusted hazard ratio in OS and PFS of the choice for chemo RFA approach to chemo-only was HR 0.43, 95% CI 0.25-0.73 and HR 0.44, 95% CI 0.28 0.71 respectively. Conclusion: CT-guided RFA combined with chemotherapy approach could improve the survival rate for NPC patients with liver metastasis. PMID- 27666884 TI - [Predictive value of early lactate area for mortality in elderly patients with septic shock]. AB - Objective: To investigate the predictive value of early lactate area for mortality in elderly patients with septic shock. Methods: From January 2012 to December 2013, a prospective study was conducted in the Department of Critical Care Medicine, Qilu Hospital of Shandong University. A total of 115 septic shock patients with age >=65 years were included in the study. Serum lactate was measured every 6 hours, the lactate indicators, including early lactate area, APACHE II score etc were recorded. Results: The overall 28-day mortality rate was 67.0%. The top three primary infection sources were lung, abdominal cavity and bloodstream. When compared to survivors, non-survivors had significantly elevated early lactate area and APACHE II score and lowered lactate clearance[(27.4+/-7.6) vs ( 20.3+/-6.5)], they were significantly more likely to have undergone mechanical ventilation, renal replacement therapy and inotropic or vasopressor support for >=3 d, and more frequently displayed signs of cardiovascular, respiratory, and renal and hepatic dysfunction (all P<0.05) .Receiver Operating Characteristic curves indicated the lactate area score displayed a strong predictive power for 28 day mortality as indicated by an AUC of 0.758 (P<0.01) and had significantly greater predictive power when compared to the initial lactate or lactate clearance (all P<0.05). Conclusions: In geriatric patients with septic shock, the early lactate area is a useful predictor for early death and showed better predictive value than other lactate indicators. PMID- 27666883 TI - [MRI findings of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions]. AB - Objective: To analyze MRI findings of renal cell carcinoma associated with Xp11.2 translocation-TFE gene fusion(Xp11.2 RCC). Methods: MR imaging features of eleven patients with pathologically-proved Xp11.2 RCC were retrospectively analyzed from December 2008 to December 2015. The following MRI features of the lesions were analyzed in the study: location, maximal diameter, signal intensity, hemorrhage, necrosis, cystic change, enhancement features and metastasis. The data was analyzed by using t test. Results: Four men and seven women (mean age, 35.2 years; age range, 15-49 years) were included. Tumors occurred in the right kidney in 5 cases and the left kidney in 6 cases. On T1WI tumors showed heterogeneously hypo-intensity and iso-intensity, hyper-intensity in 10 cases, 1 cases, respectively. On T2WI tumors showed heterogeneously slight hypo-intensity, heterogeneously slight hyper-intensity and hyper-intensity in 6 cases, 4 cases, 1 case, respectively. On DWI tumors showed hyper-intensity and heterogeneously slight hype-intensity in 2 cases, 9 cases, respectively. ADC value of the tumors were statistically significant lower than that of renal cortex(*10-3mm2/s)(1.35+/ 0.20 vs 2.09+/-0.11, P<0.05). Imaging findings were suggestive of hemorrhage(n=4) or necrosis (n=1) or cystic change (n=6) or lipid(n=1) in the tumors. On dynamic contrast-enhanced imaging, tumors showed lower signal intensity change (96%+/ 93%, 110%+/-86% and 103%+/-46%, respectively) than did renal cortex (285%+/-109%, 254%+/-97% and 225%+/-90%, respectively) (P<0.05). Tumor capsule showed in 7 cases. Enlarged lymph node was found in renal hilum in one case. Conclusion: MRI findings may show characteristic features of Xp11.2 RCC combined with patients' age and assist in preoperative correct diagnosis. PMID- 27666885 TI - [Clinical investigation of temporary heart pacemaker for emergency treatment of patients with acute and severe cardiovascular diseases]. AB - Objective: To investigate the clinical efficacy and safety of temporary heart pacemaker for emergency treatment of patients with acute and severe cardiovascular diseases. Methods: The clinical data of 147 patients with cardiac arrest or bradyarrhythmia from August 2007 to December 2015, was analyzed retrospectively in Department of internal and Emergency Medicine, People's Hospital of Henan. Based on the rescue methods, all patients were divided into two groups: observation group (80 cases, among whom, 49 cases with cardiac arrest and 31 cases with bradyarrhythmia) and control group (67 cases, among whom 39 cases with cardiac arrest and 28 cases with bradyarrhythmia). Patients in observation group received temporary heart pacemaker, and patients in control group received traditional cardio-pulmonary resuscitation and drug treatment. The rate of rescue and complications were analyzed and compared in two groups. Results: The total rescue rate in observation group was 96.3%, which was significantly higher than that in control group (44.8 %) (P<0.05). Further analysis showed that the rescue rate of patients with cardiac arrest in observation group was significantly higher than that in control group (95.1% vs 45.1%) (P<0.05), and the rescue rate of patients with bradyarrhythmia in observation group was significantly higher than that in control group (97.4% vs 44.4%) (P<0.05). Complications were observed in 4 patients: pericardial effusion (1 case ), ventricular fibrillation (1 cases) and catheter dislocation (2 cases). Conclusion: Temporary heart pacemaker was safe and effective in the treatment of patients with acute and severe cardiovascular diseases with improved rescue rate. PMID- 27666886 TI - [Prenatal ultrasound diagnosis, prognosis and chromosome analysis of fetal bowel dilatation]. AB - Objective: To investigate the relationship among the prenatal ultrasound, prognosis and chromosome results of fetal bowel dilatation. And in order to further improve the positive rate of prenatal chromosome examination operation, and reduce the risk of missed diagnosis. Methods: Ninety fetuses who were diagnosed as fetal bowel dilatation by prenatal ultrasound from June 2013 to December 2015 in the Second hospital of Jilin University were enrolled. Chromosomes were examined by amniotic cavity puncture or umbilical cord blood puncture. The change of fetus's bowel was monitored periodically by prenatal ultrasound. The normal bowel movement of newborns was a good prognosis. The abdominal X ray or barium contrast radiography was performed in the newborns who did not have normal bowel movement after delivery. Patients underwent surgery or conservative treatment after diagnosis. Fetal karyotype analysis of aborted fetus was carried out by amniotic cavity puncture and umbilical cord blood before induction of labor. Autopsy was performed after induced labor. Patients who were not continued examination in our hospital were followed up by telephone. Results: Among the 90 fetuses, there are 11 cases of duodenum dilatation, 38 cases of jejunum and ileum dilatation, 41 cases of colorectal dilatation. Ten cases of duodenum dilatation were confirmed by autopsy after induced labor, and one case was lost in follow-up. Chromosome examination revealed 3 cases of 21- three body syndrome, 1 case of 18- three body syndrome, 1 case of chromosomal translocation. In 38 cases of jejunum and ileum dilatation, bowel dilatation of 26 cases had decrease or no obvious increase with good prognosis. Six cases of induced labor, 3 cases of receive surgery after birth, 2 cases of postoperative survival, and 3 cases of loss of follow-up. Chromosome examination revealed 1 case of 21- three body syndrome and 1 case of chromosomal translocation. In 41 cases of colorectal dilatation, 29 cases had good prognosis. Five cases were aborted, 1 case of fetal death, 2 cases died within 1 month after birth, 2 cases received surgery after birth and survived after operation, and 2 cases of loss of follow-up. Conclusions: Clinical prognosis and the associated risk of chromosome abnormalities in patients with fetal bowel dilatation are different in terms of its expansion location and extent of the different, which need to a specific analysis of specific situations. PMID- 27666887 TI - [Clinical value of assisted laparoscopic ultrasonography in laparoscopic myomectomy]. AB - Objective: To explore the application value of assisted laparoscopic ultrasound in myomectomy. Methods: One hundred and fifty six patients who underwent myomectomy in Beijing Obstetrics and Gynecology Hospital from 2011 to 2013 were enrolled.The patients were randomly divided into laparoscopic ultrasound guided group (n=57), laparoscopic group (n=54) and open resection group (n=45). The patients were followed up to calculate the residue and recurrence rates of uterine fibroids by vaginal ultrasound at 6th month and 12th-18th month after the operation. The residual and recurrence rates of the three methods were calculated and compared. Results: The recurrence rate of laparoscopic ultrasound guided group wassignificantly lower than that of laparoscopic group and open resection group (P<0.01) and (P<0.01). The residual rate of laparoscopic ultrasound guided group was also lower than that of laparoscopic group(P<0.05). However, there was no difference between the residual rates of laparoscopic ultrasound guided group and open resection group (P>0.05). When compared with open resection group, no difference was found in the residual and recurrence rates of laparoscopic group. The number of myoma was proportional to the residual rate and the recurrence rate. When the number of the myoma was more than 10, most of the cases existed residue. Conclusion: The application of assisted laparoscopic ultrasound in myomectomy couldreduce the residual and recurrence rate of uterine fibroids. PMID- 27666888 TI - [Breast lymphoma ultrasound image and clinical pathological analysis]. AB - Objective: To investigate the relationship between different image sonographic findings and different pathological breast lymphoma. Methods: A total of 24 patients of breast lymphoma from the First Affiliated Hospital of Nanjing Medical University who were confirmed by pathology were retrospectively analyzed between January 2006 and December 2015.All the ultrasound and clinical pathologic features of relevant information were collected to observe the pathological changes of ultrasonographic performance. Results: Ultrasonic image can be divided into mass type and diffuse typpe .There were 10 cases of diffuse type (10/24, 41.7%), 14 cases of mass type (14/24, 58.3%) .Pathology was given priority to diffuse large B lymphoma .Sonographic findings of different classification were based on pathological histology, which were related with the lymphoma cells infiltrating location, degree, scope and different stages of progression.Mass type and diffuse type were different in the lesion range comparison.Secondary and primary breast lymphoma in ultrasound performance type had no significant difference. There were differences in the lesion distribution comparison. Conclusion: Breast lymphoma have different sonographic features based on histological features. PMID- 27666889 TI - [Effects of 0.5 Gy X-ray radiation on the profile of gene expression in MC3T3-E1 osteoblasts]. AB - Objective: To investigate the molecular mechanism of low-dose X-ray irradiation on osteoblasts by detecting the gene expression profiles of osteoblasts radiated with 0.5 Gy X-ray. Methods: Microarray analyses to value the changes of gene expression of MC3T3-E1 osteoblasts after 0.5 Gy X-ray irradiation were conducted.The end points included modulation of key markers, and pathway and gene ontology through transcriptomic profiling and bioinformatics analysis. Several major genes during osteoblasts differentiation were selected for Real-time PCR analysis. Results: 1 412 differentially expressed transcripts were identified between the radiated group and control group. Among the identified genes, 559 transcripts were up-regulated and 853 transcripts were down-regulated after irradiation.Real-time PCR analysis indicated that the mRNA expressions of Bglap rs1, Col1a2, Tgf-beta1, Lrp5, Dvl1, Map4k5 were apparently higher than that of the controls (P<0.01), whereas the Id2 and Dkk1 expression decreased under the same condition(P<0.01). Western-blot analysis indicated TGF-beta1 and Lrp-5 protein expression increased and Dkk1 expression decreased(P<0.05). Pathway analysis and gene ontology analysis revealed that focal adhesion, extracellular signaling, cytoskeletal protein binding, Wnt signal pathway, IkappaB /NF-kappaB signal pathway and growth factor receptors activities. Conclusions: Low-dose X ray radiation promoted osteoblasts differentiation in which focal adhesion, extracellular signaling, cytoskeletal protein binding, Wnt signal pathway, IkappaB /NF-kappaB signal pathway and growth factor activities might be involved. PMID- 27666890 TI - [Effects and mechanism of testosterone on the production of inflammatory cytokines and glucose uptake in co-culture of RAW264.7 macrophage and 3T3-L1 adipocytes]. AB - Objective: To investigate the effects of testosterone (T) on inflammatory cytokines (IL-6, MCP-1) production, insulin sensitivity of adipocyte and changes of macrophage phenotypes in indirect co-culture of RAW264.7 macrophages and 3T3 L1 adipocytes. Methods: 3T3-L1 preadipocytes were induced to mature in Transwell lower chamber, and then co-cultured with RAW264.7 macrophages in the upper chambers for 72 hours. Testosterone 10 MUmol/L was added into indirect co-culture for 24 h. ELISA was used to testing IL-6, MCP-1 concentrations in supernatant. Western blot was used to detecting the phosphorylation of NF kappa B, ERK1/2, and theexpression of CD16/32 and CD206. Glucose transport was assessed by[3H]2-deoxy glucose uptake in adipocytes. Results: Testosterone enhanced inflammatory cytokines (IL-6, MCP-1) production in indirect co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages, promoted the activation of ERK1/2 and nuclear factor kappa B p65, and inhibited glucose uptake in adipocytes. Testosterone facilitated the production of pro-inflammatory M1 macrophages. The above effects of testosterone can be completely reversed by PDTC, and can be partly reversed by PD98059 (70%-90%). Conclusion: NF kappa B and ERK1/2 could be the key proteins for testosterone to promote the production of inflammatory factors, to lead to insulin resistance, and to make macrophages differentiate to pro-inflammatory phenotypes in co-culture of RAW264.7 macrophages and 3T3-L1 adipocytes. PMID- 27666892 TI - [Establishment of endometriosis subcutaneous model in immunodeficient nude mice]. AB - Objective: To establish a model of endometriosis in immunodeficient nude mice and compare the outcome of the model construction between two different techniques. Methods: Eighteen nude mice were divided into 2 groups, with 9 mice in each group. All nude mice received a subcutaneous transplantation of endometrial fragments, followed by sutured the wounded skin (sutured group) or not (no sutured group). Then the success rate of the model construction, inflammation of the wounds and the animal survival rate in the two groups were analyzed. Result: In no-sutured group, the survival rate of animal and the success rate of the model construction were 9/9 and 8/9 respectively, with 8/9 survival rate and 7/9 success rate in sutured group. No significant difference was found between the two groups. And no obvious inflammation was presented in the wounds for both groups. Conclusion: It is an effective method to establish animal model of endometriosis by subcutaneous transplantation in nude mice. After transplantation, it does not affect the outcome of the survival rate of the animal and the success rate of the model construction whether we suture the wounded skin. Considering the shorter operation time, we found it's a simpler and time saving method to establish endometriosis by subcutaneously transplanting endometrial fragments in nude mice with no skin-sutured. And this model is worth of promotion. PMID- 27666891 TI - [Expression pattern of beta-amyloid in the peri-infarct area and ipsilateral thalamus of rats after focal cerebral cortex infarction]. AB - Objective: To investigate the expression pattern of beta-amyloid (Abeta) in rats after focal cerebral cortex infarction, and to identify whether the Abeta expression in the ipsilateral thalamus was directly related to focal cerebral ischemia. Methods: The distal middle cerebral artery occlusion (MCAO) was performed by electrocoagulation in rats. The rats were divided randomly into sham group (n=18) and MCAO group (n=30) . We used 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining to detect the location of cerebral infarction and Abeta expression, respectively. Results: TTC staining showed that the cerebral infarction was consistently restricted to the frontal and temporoparietal cortex. In the peri-infarct area of the MCAO group, Abeta expression began at day 2, reached the maximum level at day 7, and disappeared almost completely at day 28 after MCAO. The Abeta appeared as diffuse small dots, and was located in neurons and astrocytes at day 2 and day 28, respectively. Meanwhile, in the ipsilateral thalamus, Abeta expression began at day 3, increased markedly at day 7, and remained until day 28 after MCAO. The Abeta was located constantly in the extracellular region of the ipsilateral thalamus, and aggregated gradually from small dots to dense plaque-like deposits with the time of ischemia. Conclusions: There are dynamic changes of Abeta expression in both the peri-infarct area and the ipsilateral thalamus following MCAO. The Abeta expression in the ipsilateral thalamus is not directly related to focal cerebral ischemia. PMID- 27666893 TI - Spectroscopic Properties of Phase-Pure and Polytypic Colloidal Semiconductor Quantum Wires. AB - We report ensemble extinction and photoluminesence spectra for colloidal CdTe quantum wires (QWs) with nearly phase-pure, defect-free wurtzite (WZ) structure, having spectral line widths comparable to the best ensemble or single quantum-dot values, to the single polytypic (having WZ and zinc blende (ZB) alternations) QW values, and to those of two-dimensional quantum belts or platelets. The electronic structures determined from the multifeatured extinction spectra are in excellent agreement with the theoretical results of WZ QWs having the same crystallographic orientation. Optical properties of polytypic QWs of like diameter and diameter distribution are provided for comparison, which exhibit smaller bandgaps and broader spectral line widths. The nonperiodic WZ-ZB alternations are found to generate non-negligible shifts of the bandgap to intermediate energies between the quantum-confined WZ and ZB energies. The alternations and variations in the domain sizes result in inhomogeneous spectral line width broadening that may be more significant than that arising from the 12 13% diameter distributions within the QW ensembles. PMID- 27666894 TI - Pregnancy beyond 65: report of a unique case and discussion of a controversial issue. AB - We present the case report of a 66-year-old woman who was attended at our gynaecology department at a tertiary university hospital in Barcelona, Spain for a high-risk pregnancy and comment on the obstetric implications and bioethical issues. We retrospectively analysed clinical data about the case and bibliographic references related to the issue. The woman underwent in vitro fertilisation of donated embryos in a private centre and came to our unit at 27 weeks of gestation for pregnancy care. At 33 weeks, she presented pre-eclampsia and a caesarean section was performed. She gave birth to healthy twin boys. Four months later, she returned to our centre with the diagnosis of ovarian cancer and died 30 months after delivery. We present the clinical course and management of this pregnancy and comment on the obstetric implications, the impact on maternal and neonatal health, and bioethical issues related to assisted reproduction techniques in pregnancies beyond the natural reproductive age. PMID- 27666897 TI - SLE Neuropathy-Anything New? AB - SLE (systemic lupus erythematosus) is a multisystem autoimmune disorder of unknown aetiology which can present with myriad clinical presentation. The neurological manifestations of SLE consist of central nervous system (CNS) and peripheral nervous system manifestations (PNS). The CNS manifestations are aseptic meningitis, cerebrovascular accidents (stroke), demyelinating disorders, headache, involuntary movements like chorea, myelopathy, acute confusional states, cognitive dysfunction, mood disorder, seizures, psychosis and cranial nerve palsies.1 The PNS manifestations are Guillain Barre syndrome (GBS), autonomic disorder, mononeuropathy, polyneuropathy and plexopathy.1 Neuropathy in SLE can be clinically classified as mononeuritis multiplex and symmetrical and asymmetrical polyneuropathy. Symmetrical polyneuropathy being the most commonly seen clinical entity amongst the neuropathies in SLE. The neuropathy can be slowly progressive or acute in onset. Electrophysiologically, neuropathy is classified as axonal neuropathy, small fibre neuropathy, demyelinating neuropathy, mixed axonal-demyelinating sensorimotor polyneuropathy and plexopathy. Axonal neuropathy is further divided into sensory, sensorimotor and mononeuritis multiplex. Demyelinating neuropathy can be of two types: acute inflammatory demyelinating polyneuropathy (AIDP) and sensory demyelinating polyneuropathy. Anecdotal case reports also suggest that CIDP can occur as part of SLE neuropathy.2. PMID- 27666895 TI - Racial Differences in the Incidence of Cardiovascular Risk Factors in Older Black and White Adults. AB - OBJECTIVES: To describe the incidence of cardiovascular risk factors, or race related disparities in incidence, across the age spectrum in adults. DESIGN: Longitudinal cohort. SETTING: National sample. PARTICIPANTS: Community-dwelling black and white adults recruited between 2003 and 2007. MEASUREMENTS: Incident hypertension, diabetes mellitus, dyslipidemia and atrial fibrillation over 10 years of follow-up in 10,801 adults, stratified according to age (45-54, 55-64, 65-74, >=75). RESULTS: There was no evidence (P >= .68) of an age-related difference in the incidence of hypertension for white men (average incidence 38%), black men (48%), or black women (54%), although for white women incidence increased with age (45-54, 27%; >=75, 40%). Incidence of diabetes mellitus was lower at older ages for white men (45-54, 15%; >=75, 8%), black men (45-54, 29%; >=75, 13%), and white women (45-54, 11%; >=75, 4%), although there was no evidence (P = .11) of age-related changes for black women (average incidence 21%). For dyslipidemia, incidence for all race-sex groups was approximately 20% for aged 45 to 54 but approximately 30% for aged 54 to 64 and 65 to 74 and approximately 22% for aged 75 and older. Incidence of atrial fibrillation was low at age 45 to 54 (<5%) but for aged 75 and older was approximately 20% for whites and 11% for blacks. The incidence of hypertension, diabetes mellitus, and dyslipidemia was higher in blacks across the age spectrum but lower for atrial fibrillation. CONCLUSION: Incidence of risk factors remains high in older adults. Blacks have a higher incidence of hypertension, diabetes mellitus, and dyslipidemia after age 45, underscoring the ongoing importance of prevention of all three conditions in mid- to later life. PMID- 27666896 TI - MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1. AB - The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention. PMID- 27666898 TI - Peripheral Neuropathy in Systemic Lupus Erythematosus: Clinical and Electrophysiological Properties and their Association with Disease Activity Parameters. AB - AIM: To study clinical and electrophysiological properties of peripheral neuropathy (PN) in systemic lupus erythematosus (SLE) and their association with disease activity parameters. METHODS: A hospital-based observational study done among 50 SLE patients after informed consent. History and clinical examination including a detailed neurological examination was carried out. Blood and urine investigation were done and modified SLE disease activity index (SLEDAI)-2000 score was calculated. RESULTS: PN was found in 18 out of 50 (36%) SLE cases as defined electrophysiologically, nine had clinical and nine had subclinical neuropathy. On nerve conduction studies (NCS) 17 patients had axonal pattern. There were significant difference for mean ESR in patients with neuropathy (64.17 +/- 42.43 mm/1st hour) and without neuropathy (42.34 +/- 27.68 mm/1st hour) (P 0.033) and for mean modified SLEDAI-2000 of patients with neuropathy (15.61 +/- 10.09) and without neuropathy (6.84 +/- 6.16) (P < 0.05). CONCLUSIONS: The study suggests significant association of peripheral neuropathy in SLE patients with ESR, modified SLEDAI-2000, pyuria, pleurisy and leucopenia. PMID- 27666899 TI - Sex Differences in Cardiovascular Risk Factors among People with Diabetes in South India. AB - OBJECTIVE: To assess the sex differences in the prevalence of cardiovascular risk factors among patients with type 2 diabetes, visiting the hospital between March December 2012. METHODS: A cross-sectional study was performed among the type 2 diabetes patients attending M.V. Hospital for Diabetes, a tertiary centre specialized in diabetes care, Chennai, South India. We collected information on obesity (body mass index >=25 kg/m2), hypertension, dyslipidemia, smoking, alcohol consumption and glycemic control (HbA1c >8% considered poor control). RESULTS: Risk factors (prevalence) among 6113 (58% males; mean age 54 years) patients were obesity (68.4%), poor glycemic control (51.4%), hypertension (37.9%), dyslipidemia (34.7%), smoking (9.6%) and consumption of alcohol (10.3%), respectively. Women had a higher prevalence of obesity (75.7 vs 63.2%) and poor glycemic control while men had a higher prevalence of smoking and alcohol consumption. There were no sex differences in prevalence of hypertension and dyslipidemia. Cardiovascular risk factors were not associated with duration of diabetes. CONCLUSIONS: Cardiovascular risk factors were highly prevalent among patients with type 2 diabetes attending a tertiary care centre in South India, with different risk profiles among men and women. We recommend a gender-sensitive approach in planning interventions (counseling and treatment) to reduce the risk of cardiovascular disease. PMID- 27666900 TI - Treatment of Type 2 Diabetes with a Breakable Extended Release Gliclazide Formulation in Primary Care: The Xrise Study. AB - OBJECTIVE: This study examines whether a new, scored and breakable once daily gliclazide tablet formulation, gliclazide XR 60 mg, that enables a simple 2-steps titration, can improve glycemic control rates in the community. METHODS: In a prospective multicenter study of 4 months duration, organised in the primary care setting of urban India, type 2 diabetes patients, uncontrolled with diet alone or metformin monotherapy, received 1 (60 mg), 11/2 (90 mg), or 2 (120 mg) tablets of gliclazide XR 60 mg to achieve a target fasting plasma glucose of 126 mg/dl, or HbA1c of 7%. The primary outcome was the frequency of patients achieving glycemic control. RESULTS: Two hundred eleven investigators recruited 679 patients distributed throughout India. On intention to treat analysis, the number (%, 95% confidence interval, CI) of patients achieving glycemic control was, 526 (81.9, 78.8 to 84.6); with gliclazide XR 60 mg 1 tablet, 285 (42.0, 38.3 to 45.7); 11/2 tablets, 143 (21.1, 18.2 to 24.3); and 2 tablets, 98 (14.4, 12.0 to 17.3). Hypoglycaemic episodes were reported by 27 (4.0, 2.8 to 5.7) patients. Mean (95% CI) FPG decreased by 78.3 (73.9 to 82.7, P < 0.01) mg/dl; with 1 tablet gliclazide XR 60 mg, by 66.0 (61.1 to 70.9, P < 0.01) mg/dl; 1-1/2 tablets, by 80.1 (71.2 to 88.5, P < 0.01) mg/dl; and 2 tablets, by 106.5 (93.4 to 119.5, P< 0.01) mg/dl. HbA1c decreased by 1.5 (1.3 to 1.5, P < 0.01). CONCLUSIONS: In primary care, once daily, breakable extended release gliclazide XR 60 mg, with a simple two step titration to administer maximum recommended dosage is effective in achieving short term glycemic control with a low frequency of hypoglycaemia, in monotherapy or in combination with metformin. PMID- 27666901 TI - Clinical and Laboratory Profile of Dengue Fever. AB - OBJECTIVE: Dengue fever is one of the most common arboviral mediated outbreaks reported with increased prevalence year after year with considerable morbidity and mortality. This study was designed to assess the clinical and biochemical parameters of dengue fever patients. METHODS: Prospective observational study was undertaken among adult patients in a military hospital. Five hundred fiteen patients were studied and analysed. All patients who were NS1 antigen/IgM dengue positive were included in the study. Clinical features, hematological and biochemical parameters were noted. RESULTS: Of the 515 patients studied, majority were males (72.81%). Fever was the major symptom (100%) followed by headache (94.75%), myalgia (90.67%), retroorbital pain (18.25%), conjunctival injection (39.41%), rash (37.86%), abdominal pain (24.46%), pleural effusion (20%) and ascites (16.31%). Significant derangements in platelet (69.51%), leucocyte counts (20.19%) and serum transaminases (88.54%) were noted. Mortality rate was 0.77%. CONCLUSIONS: Fever associated with headache, retroorbital pain, erythematous morbilliform rash, conjunctival suffusion and itching in palms and soles along with thrombocytopenia, leucopenia, elevated liver transaminases should prompt a clinician on the possibility of dengue infection. Platelet transfusions have little role in management of dengue patients. PMID- 27666902 TI - A Cross-sectional Assessment of Risk Factors of Non-Communicable Diseases in a Sub-Himalayan Region of West Bengal, India Using who Steps Approach. AB - BACKGROUND: Non-communicable diseases (NCDs), principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes are the leading causes of death and disability globally. The basic element of NCD prevention is the identification of the common risk factors and their prevention and control. OBJECTIVE: To determine the prevalence of risk factors for non-communicable diseases, in Siliguri city of West Bengal, India using WHO Steps approach. METHODS: Between April 2012 to July 2012, 779 adults of 18-64 years from Siliguri city were chosen by 30-cluster sampling. They were interviewed and measurements and laboratory tests were done. RESULTS: The prevalence of behavioural risk factors like tobacco use, alcohol, unhealthy diet was 57.5%, 12.5%, 50.87% and 60.4%, respectively while that of biological risk factors like overweight, abdominal obesity and hypertension was 29.8%, 20.2% and 17.8%, respectively. The prevalence of biochemical risk categories like diabetes, hypercholesterolemia, hypertriglyceridaemia, low HDL-C was 9.1%, 17.8%, 16.6% and 67.5%, respectively. CONCLUSIONS: A high prevalence of risk factors for non-communicable diseases was found in Siliguri city which emphasizes the need of interventions to reduce these risk factors. PMID- 27666903 TI - Management of Acute Pulmonary Embolism: Consensus Statement for Indian Patients. AB - : Pulmonary embolism (PE) is an important cause of morbidity and mortality among hospitalized patients. Although the exact epidemiology of PE is not known in India, Some of the studies show that more frequently it is missed and not managed appropriately leading to significant cardiovascular morbidity and mortality. Justification and purpose: Indian guidelines for the diagnosis and treatment of acute PE are not yet formulated. The objective of this consensus statement is to propose a diagnostic and management approach for acute PE in India. PROCESS: A working group of 15 experts in the management of acute PE (cardiologists, pulmonologist, haematologist, emergency specialist and intensivists). This consensus statement makes recommendations for diagnosis and management for PE based on literature review, including Indian data. PMID- 27666904 TI - Pathogenesis and Clinical Management of Gouty Arthritis. AB - Gout, the most common of the crystal arthritides is a result of disturbed uric acid metabolism and precipitation of urate crystals in extra cellular space of joints, periarticular tissue, bones and other organs. In the West, gout affects around 1% of adult men over 45 years of age. The estimated incidence being 0.6 to 2.1 per 1000 per year, with a prevalence of 9.5 to 13.5 per 1000 persons of all ages.1 The incidence of gout has been on rise globally; potentially attributable to recent shifts in diet, lifestyle, medical care, and increased longevity.2 Gout is three to four times more common in males than in pre-menopausal females; incidence in women increases after menopause and after the age of 60, approaches that in men.3 This update aims to highlight recent developments in understanding pathogenesis of gout along with current management strategies. PMID- 27666905 TI - Writing an Abstract for a Research Manuscript: Providing an Honest, Succinct and Complete Summary. AB - is a vital part of a research paper. Besides the title, it is the most widely read section of an article. The first impressions created by the abstract on editors and reviewers can have a great influence on the fate of the article. After its publication, a reader might decide to give the article a miss, if he finds the information provided in the abstract uninteresting, irrelevant or uninspiring. An abstract should, therefore, be packed with all important relevant information about the study, so that reviewers and readers understand the rationale of the study, are assured of adequacy of the methodology employed, are informed about the important findings and appreciate the reasonable conclusions stated in the abstract. Brevity, self-sufficiency, providing complete and accurate information in an unbiased manner are some of the important characteristics of a good abstract. PMID- 27666906 TI - Striatal Toe. PMID- 27666907 TI - Diagnosis of Calciphylaxis by Imaging with Low-energy-X-rays (Mammographic Technique). PMID- 27666908 TI - Extreme Thrombocytosis. AB - A 55 years old female presented with hitherto abdominal pain and gangrenous changes of lower limbs. Patient was found to have extreme thrombocytosis. Approach to thrombocytosis is discussed here. PMID- 27666909 TI - Primary Maligant Melanoma of the Oesophagus. AB - Primary malignant melanoma of the oesophagus (PMME) is a very rare disease with poor prognosis. The median survival is about 10 months. PMME are highly aggressive biologically and metastasize early via haematogenic and lymphatic pathways. Treatment outcome is poor because malignancy is very advanced at the time of presentation. Here, we present the endoscopic features and management of PMME case. PMID- 27666911 TI - Biventricular Non-Compaction Cardiomyopathy. AB - Left ventricular non-compaction (spongy myocardium) is one of the most misclassified cardiomyopathies. It is characterised by an excessively prominent trabecular meshwork of myocardium and deep intertrabecular myocardium due to an arrest in the compaction process of the myocardial fibres. It could be isolated i.e. without any other structural heart defects or associated with congenital heart defects. The clinical manifestations are variable heart failure, arrhythmia, thromboembolic phenomena depending on extent of non-compaction of cardiac segment. PMID- 27666910 TI - Isolated Actinomycotic Swelling in Right Upper Cervical Region. AB - Cervicofacial actinomycosis is today a rare disease in our country. Isolated neck swelling due to actinomycosis is extremely rare. A case of 52 year old man with an isolated neck swelling due to actinomycosis without any discharging sinus is reported here. PMID- 27666913 TI - A Diagnosis Made by 'Facilitation'. AB - Lambert Eaton myasthenic syndrome is a presynaptic neuromuscular junction disorder, which has unique features on electrodiagnostic testing. Here we describe a middle aged lady with symmetric, progressive, areflexic weakness in lower limbs, who had the typical electrodiagnostic findings of diffuse attenuation of motor amplitudes, and increase in these amplitudes after brief exercise of the muscle sampled. PMID- 27666912 TI - Atrial Tachycardia Ablated Successfully from the Aorta. AB - We present a case of recurrent highly symptomatic atrial tachycardia. During electrophysiology (EP) study, this was found to arise close to the AV node. To avoid conduction system damage by radiofrequency (RF) ablation, the aortic cusps were mapped. The tachycardia focus was close to the non-coronary cusp and ablated safely and successfully from this site. PMID- 27666914 TI - Acute Q Fever Pneumonia. AB - Q fever is a zoonotic disease caused by Coxiella burnetii which has a worldwide distribution. Pneumonia occurs in almost half of the patients who have an acute C. burnetii infection. Less than 5-6% of community acquired pneumonia (CAP) is found to be caused by this organism. Endemicity of C. burnetii infection has been recorded in various studies carried out in our country. However there is no mention about Q fever as a cause of CAP in the various studies done to identify the aetiological agent. We report a case of acute Q fever related pneumonia and this appears to be the first reported case of pneumonia due to C. burnetii infection in India. PMID- 27666915 TI - Indoxacarb Poisoning Presenting as Methemoglobinemia and Seizure. AB - We are reporting a case of poisoning with a non-organophosphate pesticide (indoxacarb) resulting in methemoglobinemia and seizures, and successfully treated with ventilator care and intravenous ascorbic acid. Since there are limited data concerning the human toxicity of indoxacarb, physicians in emergency rooms should be aware of this rare poison and also its clinical presentations. PMID- 27666917 TI - Pioneers in Infection Prevention - Part 2. PMID- 27666916 TI - Passenger Lymphocyte Syndrome in a Renal Transplant Recipient. AB - New onset anaemia within three months after renal transplantation though not very common sometimes present as diagnostic challenge to the renal physicians. Understanding the etiology is necessary for correct management and avoiding adverse graft outcome. Passenger lymphocyte syndrome (PLS) is a rare entity of immune haemolytic anaemia that sometimes occurs in recipient of minor ABO mismatched renal transplantation. In this case report we present an AB positive renal allograft recipient who received organ from an O positive donor and developed acute haemolytic anaemia and jaundice, 19 days after renal transplantation due to PLS. PMID- 27666918 TI - Nitric Oxide (NO): Molecule of the Year 1992. PMID- 27666919 TI - Passive Euthanasia and Assisted Suicide. PMID- 27666920 TI - Unique Interaction of Saroglitazar with Insulin. PMID- 27666921 TI - Thyroid Storm Precipitated by Radioactive Iodine Therapy. PMID- 27666922 TI - Adaptive vision-based control of an unmanned aerial vehicle without linear velocity measurements. AB - In this paper, an image-based visual servo controller is designed for an unmanned aerial vehicle. The main objective is to use flow of image features as the velocity cue to compensate for the low quality of linear velocity information obtained from accelerometers. Nonlinear observers are designed to estimate this flow. The proposed controller is bounded, which can help to keep the target points in the field of view of the camera. The main advantages over the previous full dynamic observer-based methods are that, the controller is robust with respect to unknown image depth, and also no yaw information is required. The complete stability analysis is presented and asymptotic convergence of the error signals is guaranteed. Simulation results show the effectiveness of the proposed approach. PMID- 27666923 TI - Performance analysis of improved iterated cubature Kalman filter and its application to GNSS/INS. AB - In order to improve the accuracy and robustness of GNSS/INS navigation system, an improved iterated cubature Kalman filter (IICKF) is proposed by considering the state-dependent noise and system uncertainty. First, a simplified framework of iterated Gaussian filter is derived by using damped Newton-Raphson algorithm and online noise estimator. Then the effect of state-dependent noise coming from iterated update is analyzed theoretically, and an augmented form of CKF algorithm is applied to improve the estimation accuracy. The performance of IICKF is verified by field test and numerical simulation, and results reveal that, compared with non-iterated filter, iterated filter is less sensitive to the system uncertainty, and IICKF improves the accuracy of yaw, roll and pitch by 48.9%, 73.1% and 83.3%, respectively, compared with traditional iterated KF. PMID- 27666925 TI - Two Kinds of Suicide. AB - In suicidology, the common view is that 'rational' suicides occur only rarely, because the competence of people who want to end their lives is compromised by mental illness. In the Netherlands and Flanders, however, patients' requests for euthanasia or assistance in suicide are granted in 5300 and 1400 cases a year respectively, and in all these cases at least two doctors have confirmed the patient's competence. The combination of these two findings is puzzling. In other countries one would expect at least some of these people to end their own lives. The article argues that we can distinguish between two types of suicide with clustering characteristics. In cases of the first type, the agent doesn't carefully plan his action, doesn't communicate his plans to relatives or others, and uses violent means. In such cases it is reasonable to presume lack of competence. The other type has the opposite characteristics. The most plausible explanation of our problem is that suicides of the second kind are invisible to suicidology, because they tend not to be registered as suicides at all. PMID- 27666926 TI - Postoperative excessive gain in visceral adipose tissue as well as body mass index are associated with adverse outcomes of an ileal pouch. AB - BACKGROUND: There are no published studies on the impact of visceral adipose tissue (VAT) change on outcomes of restorative proctocolectomy and ileal pouch anal anastomosis (IPAA). The aim of this historic cohort study was to evaluate the impact of excessive VAT gain on the outcomes of inflammatory bowel disease (IBD) patients with IPAA. METHODS: We evaluated all eligible patients with at least two sequential CT scans after pouch construction from our prospectively maintained Pouchitis Registry between 2002 and 2014. The visceral fat area (VFA) was measured on CT images. The study group comprised patients with a significant VAT gain (> 15%), and the control group was those without. The adverse outcomes of the pouch were defined as the new development of chronic pouch inflammation (chronic pouchitis, chronic cuffitis or Crohn's disease of the pouch), anastomotic sinus and the combination of above (the composite adverse outcome) or pouch failure, after the inception CT. RESULTS: Of 1564 patients in the Registry, 59 (3.8%) with at least 2 CT scans after pouch surgery were included. Twenty-nine patients (49.2%) were in the study group, and 30 (50.8%) were in the control group. The median duration from the inception to the latest CT was 552 (range: 31 2598) days for the entire cohort. We compared the frequency of new chronic pouch inflammation (13.8% vs 3.3%, P = 0.195), new pouch sinus (10.3% vs 0%, P = 0.112), composite adverse pouch outcome (24.1% vs 3.3%, P = 0.026) or pouch failure (10.3% vs 6.7%, P = 0.671) between the two groups. Kaplan-Meier plot for time-to-pouch failure between the pouch patients with or without excessive body mass index (BMI) gain (> 10%) showed statistical difference (P = 0.011). Limited stepwise multivariate analysis showed that excessive VAT gain (odds ratio = 12.608, 95% confidence interval: 1.190-133.538, P = 0.035) was an independent risk factor for the adverse pouch comes. CONCLUSIONS: In this cohort of ileal pouch patients, excessive VAT gain as well as gain in BMI after pouch construction was found to be associated with poor long-term outcomes. PMID- 27666924 TI - Integrated microRNA and protein expression analysis reveals novel microRNA regulation of targets in fetal down syndrome. AB - Down syndrome (DS) is caused by trisomy of human chromosome 21 and is associated with a number of deleterious phenotypes. To investigate the role of microRNA (miRNA) in the regulation of DS, high-throughput Illumina sequencing technology and isobaric tagging for relative and absolute protein quantification analysis were utilized for simultaneous expression profiling of miRNA and protein in fetuses with DS and normal fetuses. A total of 344 miRNAs were associated with DS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the proteins found to be differentially expressed. Functionally important miRNAs were determined by identifying enriched or depleted targets in the transcript and the protein expression levels were consistent with miRNA regulation. The results indicated that GRB2, TMSB10, RUVBL2, the hsa-miR 329 and hsa-miR-27b, hsa-miR-27a targets, and MAPK1, PTPN11, ACTA2 and PTK2 or other differentially expressed proteins were connected with each other directly or indirectly. Integrative analysis of miRNAs and proteins provided an expansive view of the molecular signaling pathways in DS. PMID- 27666927 TI - Conserved and divergent expression patterns of markers of axial development in the laboratory opossum, Monodelphis domestica. AB - BACKGROUND: Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short-tailed opossum, a metatherian. RESULTS: Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post-coitus. CONCLUSIONS: Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176-1188, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27666929 TI - Prolongation of overall treatment time as a cause of treatment failure in early breast cancer: An analysis of the UK START (Standardisation of Breast Radiotherapy) trials of radiotherapy fractionation. AB - BACKGROUND: Tests of tumour treatment time effect in patients prescribed post operative radiotherapy for early breast cancer have focussed on time to start of radiotherapy rather than overall treatment time. The START randomised trials of radiotherapy fractionation provide an opportunity to directly estimate the effect of treatment acceleration. METHODS: Between 1986 and 2002, a total of 5861 women with early breast cancer were recruited into the UK START pilot (START-P), START A and START-B randomised trials. START-P and START-A tested 13 fractions of 3.0 3.3Gy against 25 fractions of 2.0Gy with a fixed treatment duration of 5weeks for all schedules; START-B tested 15 fractions of 2.67Gy in 3weeks against 25 fractions of 2.0Gy over 5weeks. Estimates of the effect of length of treatment for local-regional relapse and for a measure of late normal tissue effects (change in photographic breast appearance, for patients following breast conserving surgery) were obtained from Cox proportional hazards regression analyses stratified according to trial. RESULTS: At a median follow-up of 10years, 444/5831 (7.6%) patients with data available had a local-regional relapse, and 1135/3185 (35.6%) had mild or marked change in photographic breast appearance by 5years. Adjusting for prognostic factors, the estimate of the overall treatment time effect for local-regional relapse was 0.60Gy/day (95%CI 0.10 to 1.18Gy/day, p=0.02), and 0.14Gy/day (95%CI -0.09 to 0.34Gy/day, p=0.29) for change in photographic breast appearance. CONCLUSIONS: Combined analysis of the START trials generates the hypothesis that overall treatment time is a significant determinant of local cancer control after adjuvant whole breast radiotherapy, with approximately 0.6Gy per day 'wasted' in compensating for tumour cell proliferation. PMID- 27666928 TI - The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining. AB - BACKGROUND AND PURPOSE: PU-H71 is a purine-scaffold Hsp90 inhibitor developed to overcome limitations of conventional Hsp90 inhibitors. This study was designed to investigate the combined effect of PU-H71 and heavy ion irradiation on human tumor and normal cells. MATERIALS AND METHODS: The effects of PU-H71 were determined by monitoring cell survival by colony formation, and DNA double-strand break (DSB) repair by gamma-H2AX foci and immuno-blotting DSB repair proteins. The mode of cell death was evaluated by sub-G1 DNA content (as an indicator for apoptosis), and mitotic catastrophe. RESULTS: PU-H71 enhanced heavy ion irradiation-induced cell death in three human cancer cell lines, but the drug did not radiosensitize normal human fibroblasts. In irradiated tumor cells, PU-H71 increased the persistence of gamma-H2AX foci, and it reduced RAD51 foci and phosphorylated DNA-PKcs, key DSB repair proteins involved in homologous recombination (HR) and non-homologous end joining (NHEJ). In some tumor cell lines, PU-H71 altered the sub-G1 cell fraction and mitotic catastrophe following carbon ion irradiation. CONCLUSION: Our results demonstrate that PU-H71 sensitizes human cancer cells to heavy ion irradiation by inhibiting both HR and NHEJ DSB repair pathways. PU-H71 holds promise as a radiosensitizer for enhancing the efficacy of heavy ion radiotherapy. PMID- 27666931 TI - Nonivamide, a capsaicin analogue, exhibits anti-inflammatory properties in peripheral blood mononuclear cells and U-937 macrophages. AB - SCOPE: Inflammation-related diseases are a worldwide problem. The counteraction of inflammation with compounds activating the trigeminal nerve is one strategy to fight these diseases. Known trigeminally active compounds found in black or red pepper are the tingling t-pellitorine, the pungent capsaicin, and the less pungent nonivamide. The presented study compares the anti-inflammatory potential of nonivamide to the two known anti-inflammatory compounds, elucidating the mechanism of action and the role of transient receptor protein (TRP) channels. METHODS AND RESULTS: Primary peripheral blood mononuclear cells (PBMCs) and U-937 macrophages were stimulated with 1 MUg/mL LPS from Escherichia coli (EC-LPS) to induce inflammation. Nonivamide attenuated the EC-LPS induced release of IL-6 and TNF-alpha in PBMCs and U-937 macrophages determined by magnetic bead kit analysis. This anti-inflammatory mechanism was independent from nuclear factor kappa B pathway but mitogen-activated protein kinase (MAPK) pathway may be involved. In addition, cotreatment of U-937 with the trigeminally active compound and an antagonist of TRPV1 or TRPA1 abolished the anti-inflammatory activity. CONCLUSIONS: Nonivamide possessed similar anti-inflammatory potential as capsaicin and t-pellitorine. In U-937 macrophages, the tested compounds exploited an anti-inflammatory effect by inhibiting the EC-LPS induced activation of the MAPK pathway. In addition, the TRP channel activation plays a role in the anti inflammatory capacity of capsaicin and nonivamide. PMID- 27666932 TI - Tissue-specific selenium accumulation and toxicity in adult female Xenopus laevis chronically exposed to elevated dietary selenomethionine. AB - Selenium (Se) is a developmental toxicant that is also capable of altering the bioenergetic and endocrine status of adult fish. To date, aquatic ecotoxicological research has predominantly focused on the toxic effects of Se in fish, and minimal information has been published related to amphibians. The objective of the present study was to investigate the potential toxicity associated with chronically elevated dietary Se consumption in adult female amphibians utilizing the model species Xenopus laevis. Adult X. laevis females were fed a diet augmented with L-selenomethionine at measured concentrations of 0.7 ug Se/g (control), 10.9 ug Se/g, 30.4 ug Se/g, or 94.2 ug Se/g dry mass for 68 d, after which they were bred with untreated males. Ovary, egg, liver, muscle, and blood samples were collected from female frogs after completion of the exposure period and subsequent breeding to ascertain Se tissue distribution, muscle and liver triglyceride and glycogen levels, and plasma cortisol concentrations. The concentrations of Se measured in female tissues excluding the liver were significantly increased in proportion with dietary intake. No significant differences were observed among treatment groups with respect to biometric indices, energy stores, or stress response of adult female X. laevis after Se exposure, which suggests that this amphibian species is capable of accumulating substantial quantities of this element in their tissues with no adverse effects on fitness. Environ Toxicol Chem 2017;36:1047-1055. (c) 2016 SETAC. PMID- 27666933 TI - New and Old Hot Drug Targets in Tuberculosis. AB - Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis. The World Health Organization publishes global tuberculosis reports annually in order to provide the latest information in the surveillance of drug resistance. Given the alarming rise of resistance to antitubercular drugs worldwide, finding new cellular targets and developing new analogues or new compounds with greater potency against already known targets are both important aspects in fighting drug-sensitive and drug-resistant M. tuberculosis strains. In this context, the introduction of the phenotypic screens as an efficient tool for the identification of active compounds for tuberculosis drug discovery has improved the possibility to find new effective targets. With this review we describe the state of art of the currently well validated antitubercular drug targets as well as the advances in discovery of new ones. The main targets will be discussed starting from the oldest such as the enoyl reductase InhA which is constantly repurposed with new inhibitors, through the well assessed targets like the gyrase, the ATP synthetase or the RNA polymerase, up to the hot promiscuous targets decaprenylphosphoryl-Dribose oxidase DprE1 and the mycolic acid transporter MmpL3, or the newly validated and promising targets like the CTP synthetase. PMID- 27666934 TI - miRNAs in Melanoma: Tumor Suppressors and Oncogenes with Prognostic Potential. AB - MicroRNAs (miRNAs), which are small non-coding RNA molecules that post transcriptionally regulate the expression of target genes, control the vast majority of cellular events, including proliferation, differentiation, survival, senescence, autophagy, metabolism and genome stability. Even slight alterations in miRNA expression levels may induce the development of pathological states, including cancer. Several studies have already demonstrated the importance of miRNAs in the regulation of melanocytes. Upregulation of oncogenic miRNAs (oncomiRs), mainly by amplification and translocation of miRNA genes, and downregulation of oncosuppressor miRNAs (anti-oncomiRs) by deletion and other mutations, promoter methylation and abnormal processing contributes to melanoma initiation and progression. At each phase of melanoma progression, tumor cells exhibit distinct profiles of miRNA expression, as compared with normal melanocytes. Moreover, as miRNAs are stable molecules that can be identified in bodily fluids, such as blood and saliva, they can serve as potent non-invasive prognostic markers of disease progression and response to therapy. This review summarizes recent findings regarding miRNA-mediated control of melanocytes and melanoma development, and presents miRNAs as prognostic markers for this disease. PMID- 27666935 TI - Clinical exome sequencing in early-onset generalized dystonia and large-scale resequencing follow-up. AB - BACKGROUND: Dystonia is clinically and genetically heterogeneous. Despite being a first-line testing tool for heterogeneous inherited disorders, whole-exome sequencing has not yet been evaluated in dystonia diagnostics. We set up a pilot study to address the yield of whole-exome sequencing for early-onset generalized dystonia, a disease subtype enriched for monogenic causation. METHODS: Clinical whole-exome sequencing coupled with bioinformatics analysis and detailed phenotyping of mutation carriers was performed on 16 consecutive cases with genetically undefined early-onset generalized dystonia. Candidate pathogenic variants were validated and tested for cosegregation. The whole-exome approach was complemented by analyzing 2 mutated yet unestablished causative genes in another 590 dystonia cases. RESULTS: Whole-exome sequencing detected clinically relevant mutations of known dystonia-related genes in 6 generalized dystonia cases (37.5%), among whom 3 had novel variants. Reflecting locus heterogeneity, identified unique variants were distributed over 5 genes (GCH1, THAP1, TOR1A, ANO3, ADCY5), of which only 1 (ANO3) was mutated recurrently. Three genes (GCH1, THAP1, TOR1A) were associated with isolated generalized dystonia, whereas 2 (ANO3, ADCY5) gave rise to combined dystonia-myoclonus phenotypes. Follow-up screening of ANO3 and ADCY5 revealed a set of distinct variants of interest, the pathogenicity of which was supported by bioinformatics testing and cosegregation work. CONCLUSIONS: Our study identified whole-exome sequencing as an effective strategy for molecular diagnosis of early-onset generalized dystonia and offers insights into the heterogeneous genetic architecture of this condition. Furthermore, it provides confirmatory evidence for a dystonia-relevant role of ANO3 and ADCY5, both of which likely associate with a broader spectrum of dystonic expressions than previously thought. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27666937 TI - Cryptococcus laurentii infection in a patient with cutaneous leishmaniasis. PMID- 27666936 TI - Atmospheric temperature and pressure influence the onset of spontaneous pneumothorax. AB - BACKGROUND: The aim of the study was to examine the influence of the changes in the atmospheric temperature (ATemp) and the atmospheric pressure (APres) on the occurrence of a spontaneous pneumothorax (SP). PATIENTS AND METHODS: From January 2000 to March 2014, 192 consecutive SP events were examined. The ATemp and APres data at the onset of SP, as well as those data at 12, 24, 36, 48, 60, and 72 h prior to the onset time, were analyzed. RESULTS: The frequencies of SP occurrence were not statistically different according to the months or seasons, but were statistically different according to the time period (P < .01) and SP events occurred most frequently from 12:00 to 18:00. SP events frequently occurred at an ATemp of 25 degrees Celsius or higher. There was a significantly negative correlation between the APres and the ATemp at the SP onset time. The values of change in the APres from 36 to 24 h prior to SP onset were significantly lower than the preceding values. CONCLUSIONS: In this study, we observed that a SP event was likely to occur in the time period from 12:00 to 18:00, at an ATemp of 25 degrees Celsius or higher, and at 24-36 h after a drop of APres. PMID- 27666940 TI - Monitoring potential adverse event rate differences using data from blinded trials: the canary in the coal mine. AB - The development of drugs and biologicals whose mechanisms of action may extend beyond their target indications has led to a need to identify unexpected potential toxicities promptly even while blinded clinical trials are under way. One component of recently issued FDA rules regarding safety reporting requirements raises the possibility of breaking the blind for pre-identified serious adverse events that are not the clinical endpoints of a blinded study. Concern has been expressed that unblinding individual cases of frequently occurring adverse events could compromise the overall validity of the study. However, if external information is available about adverse event rates among patients not receiving the test product in populations similar to the study population, then it may be possible to address the potential for elevated risk without unblinding the trial. This article describes a Bayesian approach for determining the likelihood of elevated risk suitable binomial or Poisson likelihoods that applies regardless of the metric used to express the difference. The method appears to be particularly appropriate for routine monitoring of safety information for project development programs that include large blinded trials. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27666939 TI - FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality. AB - During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells. ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s). Several strategies have been utilized to generate fully afucosylated antibodies. A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans. However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo. Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation. Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media. Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities. Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcgammaRIII-binding and ADCC for an antibody. Biotechnol. Bioeng. 2017;114: 632-644. (c) 2016 Wiley Periodicals, Inc. PMID- 27666941 TI - Optimal feeding frequency of captive head-started green turtles (Chelonia mydas). AB - Optimal feeding frequency was investigated to improve head-started propagation programme of juvenile green turtles (Chelonia mydas). The 15-day-old turtles (25 26 g body weight) were fed for ad libitum intake at one (1MD), two (2MD), three (3MD) or four (4MD) meals daily over a 3-month trial. Responses in growth, feed utilization, faecal characteristics, haematological parameters and carapace elemental composition were used to compare treatment effects. At the end of the feeding trial, no treatment had induced mortality. Growth performance in terms of weight gain and specific growth rate was similar in turtles fed 2MD, 3MD or 4MD (p > 0.05), but 1MD differed from these (p < 0.05), and feeding at excess frequency (3MD and 4MD) increased the within-group size variation. Turtles fed 2MD had significantly lower feed intake than in 3MD and 4MD groups, but the feed conversion ratios were similar. Faecal digestive enzyme analysis indicated higher catabolism of lipid and protein in the deprivation group (1MD), when compared with turtles fed at least twice daily. The feeding frequency did not affect the specific activities of carbohydrate-digesting enzymes. The results on enzymes activities were corroborated by the transition enthalpy characteristics of faeces, indicating nutrients remaining after digestion. The 2MD treatment also improved the haematological characteristics and the carapace quality, relative to low or excess feeding. Overall, the findings indicate that feeding juvenile green turtles twice a day is the preferred option in their head-started propagation. This promotes growth, reduces feed consumption, and improves health and carapace quality. PMID- 27666938 TI - Proteomic approaches to quantify cysteine reversible modifications in aging and neurodegenerative diseases. AB - Cysteine is a highly reactive amino acid and is subject to a variety of reversible post-translational modifications (PTMs), including nitrosylation, glutathionylation, palmitoylation, as well as formation of sulfenic acid and disulfides. These modifications are not only involved in normal biological activities, such as enzymatic catalysis, redox signaling, and cellular homeostasis, but can also be the result of oxidative damage. Especially in aging and neurodegenerative diseases, oxidative stress leads to aberrant cysteine oxidations that affect protein structure and function leading to neurodegeneration as well as other detrimental effects. Methods that can identify cysteine modifications by type, including the site of modification, as well as the relative stoichiometry of the modification can be very helpful for understanding the role of the thiol proteome and redox homeostasis in the context of disease. Cysteine reversible modifications however, are challenging to investigate as they are low abundant, diverse, and labile especially under endogenous conditions. Thanks to the development of redox proteomic approaches, large-scale quantification of cysteine reversible modifications is possible. These approaches cover a range of strategies to enrich, identify, and quantify cysteine reversible modifications from biological samples. This review will focus on nongel-based redox proteomics workflows that give quantitative information about cysteine PTMs and highlight how these strategies have been useful for investigating the redox thiol proteome in aging and neurodegenerative diseases. PMID- 27666942 TI - No adverse effects of transgenic maize on population dynamics of endophytic Bacillus subtilis strain B916-gfp. AB - Endophytic bacterial communities play a key role in promoting plant growth and combating plant diseases. However, little is known about their population dynamics in plant tissues and bulk soil, especially in transgenic crops. This study investigated the colonization of transgenic maize harboring the Bacillus thuringiensis (Bt) cry1Ah gene by Bacillus subtilis strain B916-gfp present in plant tissues and soil. Bt and nontransgenic maize were inoculated with B916-gfp by seed soaking, or root irrigation under both laboratory greenhouse and field conditions. During the growing season, B916-gfp colonized transgenic as well as nontransgenic plants by both inoculation methods. No differences were observed in B916-gfp population size between transgenic and nontransgenic plants, except at one or two time points in the roots and stems that did not persist over the examination period. Furthermore, planting transgenic maize did not affect the number of B916-gfp in bulk soil in either laboratory or field trials. These results indicate that transgenic modification of maize with the cry1Ah gene has no influence on colonization by the endophytic bacteria B916-gfp present in the plant and in bulk soil. PMID- 27666943 TI - Disease Characteristics and Electromyographic Findings of Nonsurgery-Related Unilateral Vocal Fold Paralysis. AB - OBJECTIVE: The detailed characteristics and prognosis of nonsurgery-related unilateral vocal fold paralysis (NSUVFP) are currently unclear. This study evaluated the extent of laryngeal nerve lesions and the individual characteristics for patients with NSUVFP. STUDY DESIGN: Retrospective, case series. METHODS: Patients with unilateral vocal fold paralysis (UVFP) were evaluated using videolaryngostroboscopy and quantitative laryngeal electromyography. The side of nerve lesions, involvement of the external branch of the superior laryngeal nerve (eSLN), and complete vocal fold motion recovery were evaluated after >= 6 month follow-up. RESULTS: A total of 207 UVFP patients were recruited, including 153 surgery-related UVFP and 54 NSUVFP patients. Thirty four (63%) and 20 (37%) NSUVFP patients were further assigned to idiopathic and nonsurgery-related-nonidiopathic (NSNI) groups, respectively. In the idiopathic group, eSLN lesions occurred in all six (100%) patients with right-side paralysis, but in only six of 28 (21%) patients with left-side paralysis (P < 0.001). The turn frequency of the paralyzed thyroarytenoid-lateral cricoarytenoid muscle complex is lower in the NSNI group (333.1 +/- 192.1) compared with the idiopathic group (490.2 +/- 255.1) (P = 0.02). The probability of complete vocal fold motion recovery did not differ among groups (P > 0.05). CONCLUSION: Idiopathic and NSNI UVFP have different clinical presentations defined by laryngeal electromyography. NSNI UVFP had more severe denervation changes compared with idiopathic UVFP. These results may support two pathogenic mechanisms for idiopathic UVFP: 1) neuropathy specifically involving left recurrent laryngeal nerve (RLN), and 2) neuropathy affecting nerves proximal to the RLN. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1381-1387, 2017. PMID- 27666944 TI - Validating Body Fat Assessment by Bioelectric Impedance Spectroscopy in Taiwanese Hemodialysis Patients. AB - OBJECTIVE: Obesity is becoming increasingly common in hemodialysis (HD) patients and is associated with inflammation and increased mortality. The primary aim of the present study was to evaluate the accuracy and variability of the bioimpedance device in measuring body fat in Taiwanese dialysis patients. DESIGN: Cross-sectional study. SUBJECTS: One hundred twenty-two adult patients receiving HD in a single hospital in Taiwan. SETTING: We compared the results of fat mass (FM) measured by dual-energy x-ray absorptiometry (DEXA) and bioelectrical impedance spectroscopy device (Body composition monitor, BCM). MAIN OUTCOME MEASUREMENT: FM measured by BCM was calculated by subtracting fat-free mass (FFM) from body mass assuming fractional hydration of FFM of 0.73 or the proprietary prediction equations from the BCM model. RESULTS: Assessment of whole-body composition showed that percentage FM measured using the 2 techniques was highly correlated when using the BCM model or estimating from total body water using constant (0.73) hydration (r = 0.87, P < .001). There was no evident difference in measurement between patients gender. The Bland-Altman plot also showed good agreement of percentage of FM (t = 3.82; P < .001). In female patients, it was found that BCM significantly underestimated mean FM as compared to DEXA. However, the mean differences of the estimates between the methods were small (0.35 +/- 3.00 kg) and with Bland-Altman plot the limits of agreements were -5.5 to 6.2 kg (P = .40) for FM in female patients. CONCLUSIONS: Using DEXA as the reference test, BCM is a valid tool for the assessment of total body fat in HD patients. Hence, it may provide a more accessible tool for early detection of changes in body composition in these high-risk patients. PMID- 27666945 TI - Association Between Serum Leptin Level and Mortality in Kidney Transplant Recipients. AB - OBJECTIVE: Leptin is a hormone made by adipocytes and associated with hypertension, inflammation, and coronary artery disease. Low serum leptin level was associated with higher risk of death in patients with advanced chronic kidney disease. Little is known about the association of serum leptin with outcomes in kidney transplant recipients. DESIGN: Prospective prevalent cohort. SETTING AND SUBJECT: We collected sociodemographic and clinical parameters, medical and transplant history, and laboratory data of 979 prevalent kidney transplant recipients. Associations between serum leptin level and death with a functioning graft, all-cause death, and death-censored graft loss over a 6-year follow-up period were examined in survival models. RESULTS: Serum leptin levels showed moderate negative correlation with eGFR (R = -0.21, P < .001) and positive correlations with BMI (R = 0.48, P < .001) and C-reactive protein (R = 0.20, P < .001). Each 10 ng/mL higher serum leptin level was associated with 7% lower risk of death with functioning graft (hazard ratio [HR] (95% confidence interval [CI]), 0.93 (0.87-0.99)), and this association persisted after adjustment for confounders: HR (95% CI), 0.90 (0.82-0.99). Similar associations were found with all-cause death as outcome. The association between serum leptin level and risk of graft loss was nonlinear, and only low serum leptin level was associated with higher risk of graft loss. CONCLUSIONS: In prevalent kidney transplant recipients, lower serum leptin was an independent predictor of death. PMID- 27666946 TI - Health informatics model for helminthiasis in Thailand. AB - At the beginning of the new millennium, helminth infections continue to be prevalent, particularly among impoverished populations. This study attempts to create the first health informatics model of helminthiasis in Thailand. The authors investigate how a health informatics model could be used to predict the control and eradication in a national control campaign. Fish-borne helminthiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of South-East Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The epicentre of this disease is located in north-east Thailand, where high prevalence coexists with a high incidence of cholangiocarcinoma (CHCA). The current report was conducted to determine a mathematical model of surveillance for helminthiasis while also using a geographic information system. The fish borne helminthiasis model or the predicted equation was Y1 = 3.028 + 0.020 (elevation) - 2.098 (clay). For soil-transmitted helminthiasis, the mathematical model or the predicted equation was Y2 = -1.559 + 0.005 (rainfall) + 0.004 (elevation) - 2.198 (clay). The Ministry of Public Health has concluded that mass treatment for helminthiasis in the Thai population, targeting high-risk individuals, may be a cost-effective way to allocate limited funds. This type of approach, as well as further study on the correlation of clinical symptoms with environmental and geographic information, may offer a novel strategy to the helminth crisis. PMID- 27666948 TI - Incontinentia pigmenti with retinal vascular anomaly and deletion of exons 4-10 in NEMO. PMID- 27666947 TI - Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment. AB - MDM2 and XIAP are mutually regulated. Binding of MDM2 RING protein to the IRES region on XIAP mRNA results in MDM2 protein stabilization and enhanced XIAP translation. In this study, we developed a protein-RNA fluorescence polarization (FP) assay for high-throughput screening (HTS) of chemical libraries. Our FP-HTS identified eight inhibitors that blocked the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation. The compound-induced MDM2 downregulation resulted not only in inhibition of XIAP expression, but also in activation of p53, which contributed to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo. Importantly, one of the MDM2/XIAP inhibitors, MX69, showed minimal inhibitory effect on normal human hematopoiesis in vitro and was very well tolerated in animal models. PMID- 27666949 TI - Biocompatibility of three new calcium silicate-based endodontic sealers on human periodontal ligament stem cells. AB - AIM: To evaluate the biocompatibility of three calcium silicate-based endodontic sealers, Bioroot BC Sealer (Septodont, Saint-Maur-des-Fosses, France), Endoseal MTA (EndoSeal, Maruchi, Seoul, Korea) and Nano-ceramic Sealer (B&L Biotech, Fairfax, VA, USA) (NCS), on human periodontal ligament stem cells (hPDLSCs). METHODOLOGY: Human periodontal ligament stem cells were cultured in the presence of various endodontic sealer eluates for 24 h. Cell viability was determined using the MTT assay. Cell death and changes in phenotype induced by the set endodontic sealer eluates were evaluated through flow cytometry. Also, an in vitro scratch wound-healing model was used to determine their effects in cell migration. Finally, to assess cell morphology and attachment to the different sealers, hPDLSCs were directly seeded onto the material surfaces and analysed by scanning electron microscopy (SEM). One-way analysis of variance (anova) followed by a Bonferroni post-test was performed (P < 0.05). RESULTS: At 24 h, cell spreading was evident in the presence of Bioroot BC Sealer (BR) and Nano-ceramic Sealer (NCS), but not Endoseal MTA (ES). At 72 h, BR and NCS exhibited high and moderate cell proliferation, respectively, whereas ES revealed low rates of cell proliferation (P < 0.05). Similar results were obtained in a cell death assay. In addition, hPDLSCs maintained their mesenchymal phenotype in all conditions although their capacity to migrate was higher in the presence of BR. Finally, SEM studies revealed a good degree of proliferation, cell spreading and attachment, especially when using BR and NCS discs. CONCLUSIONS: BR and NCS were associated with better cytocompatibility than ES. Further in vitro and in vivo investigations are required to confirm the suitability of these calcium silicate based endodontic sealers for clinical application. PMID- 27666951 TI - A Programmable Signaling Molecular Recognition Nanocavity Prepared by Molecular Imprinting and Post-Imprinting Modifications. AB - Inspired by biosystems, a process is proposed for preparing next-generation artificial polymer receptors with molecular recognition abilities capable of programmable site-directed modification following construction of nanocavities to provide multi-functionality. The proposed strategy involves strictly regulated multi-step chemical modifications: 1) fabrication of scaffolds by molecular imprinting for use as molecular recognition fields possessing reactive sites for further modifications at pre-determined positions, and 2) conjugation of appropriate functional groups with the reactive sites by post-imprinting modifications to develop programmed functionalizations designed prior to polymerization, allowing independent introduction of multiple functional groups. The proposed strategy holds promise as a reliable, affordable, and versatile approach, facilitating the emergence of polymer-based artificial antibodies bearing desirable functions that are beyond those of natural antibodies. PMID- 27666950 TI - Mentor-mentee interaction and laboratory social environment: Do they matter in doctoral students' publication productivity? AB - We explored the social shaping of science at the micro-level reality of face-to face interaction in one of the traditional places for scientific activities-the scientific lab. We specifically examined how doctoral students' perception of their: (i) interaction with doctoral mentors (MMI) and (ii) lab social environment (LSE) influenced productivity. Construed as the production of peer reviewed articles, we measured productivity using total number of articles (TOTAL), number of articles with impact factor greater than or equal to 4.00 (IFGE4), and number of first-authored articles (NFA). Via face-to-face interviews, we obtained data from n = 210 molecular biology Ph.D. students in selected universities in Japan, Singapore, and Taiwan. Additional productivity data (NFA) were obtained from online bibliometric databases. To summarize the original 13 MMI and 13 LSE semantic-differential items which we used to measure students' perceptions, principal component (PC) analyses were performed. The results were smaller sets of 4 MMI PCs and 4 LSE PCs. To identify which PCs influenced publication counts, we performed Poisson regression analyses. Although perceived MMI was not linked to productivity, perceived LSE was linked: Students who perceived their LSE as intellectually stimulating reported high levels of productivity in both TOTAL and IFGE4, but not in NFA. Our findings not only highlight how students' perception of their training environment factors in the production of scientific output, our findings also carry important implications for improving mentoring programs in science. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):130-144, 2017. PMID- 27666953 TI - Role of work uniform in alleviating perceptual strain among construction workers. AB - This study aims to examine the benefits of wearing a new construction work uniform in real-work settings. A field experiment with a randomized assignment of an intervention group to a newly designed uniform and a control group to a commercially available trade uniform was executed. A total of 568 sets of physical, physiological, perceptual, and microclimatological data were obtained. A linear mixed-effects model (LMM) was built to examine the cause-effect relationship between the Perceptual Strain Index (PeSI) and heat stressors including wet bulb globe temperature (WBGT), estimated workload (relative heart rate), exposure time, trade, workplace, and clothing type. An interaction effect between clothing and trade revealed that perceptual strain of workers across four trades was significantly alleviated by 1.6-6.3 units in the intervention group. Additionally, the results of a questionnaire survey on assessing the subjective sensations on the two uniforms indicated that wearing comfort was improved by 1.6 1.8 units when wearing the intervention type. This study not only provides convincing evidences on the benefits of wearing the newly designed work uniform in reducing perceptual strain but also heightens the value of the field experiment in heat stress intervention studies. PMID- 27666952 TI - Risk factors for central line-associated bloodstream infection in pediatric oncology patients with a totally implantable venous access port: A cohort study. AB - BACKGROUND: Totally implantable venous access ports (TIVAPs) are used for prolonged central venous access, allowing the infusion of chemotherapy and other fluids and improving the quality of life of children with cancer. TIVAPs were developed to reduce the infection rates associated with central venous catheters; however, infectious events remain common and have not been fully investigated in pediatric oncology patients. PROCEDURE: A retrospective cohort was formed to investigate risk factors for central line-associated bloodstream infection (CLABSI) in pediatric cancer patients. Sociodemographic, clinical, and TIVAP insertion-related variables were evaluated, with the endpoint being the first CLABSI. A Kaplan-Meier analysis was performed to determine CLABSI-free catheter survival. RESULTS: Overall, 188 children were evaluated over 77,541 catheter days, with 94 being diagnosed with CLABSI (50%). Although coagulase-negative staphylococci were the pathogens most commonly isolated, Gram-negative microorganisms (46.8%) were also prevalent. In the multivariate analysis, factors that increased the risk for CLABSI were TIVAP insertion prior to chemotherapy (risk ratio [RR] = 1.56; P < 0.01), white blood cell count less than 1,000 mm-3 on the day of implantation (RR = 1.64; P < 0.01), and chronic malnutrition (RR = 1.41; P < 0.05). Median time without CLABSI following TIVAP insertion was 74.5 days. CONCLUSIONS: Risk factors for CLABSI in pediatric cancer patients with a TIVAP may be related to the severity of the child's condition at catheter insertion. Insertion of the catheter before chemotherapy and unfavorable conditions such as malnutrition and bone marrow aplasia can increase the risk of CLABSI. Protocols must be revised and surveillance increased over the first 10 weeks of treatment. PMID- 27666954 TI - Multicystic dysplastic kidney: Assessment of the need for renal scintigraphy and the safety of conservative treatment. AB - OBJECTIVES: To assess the need for implementing renal scintigraphy in the diagnosis of the multicystic dysplastic kidney (MCDK) and the safety of its conservative treatment. MATERIAL AND METHODS: A retrospective study of patients with unilateral MCDK was conducted at our centre from January 2005 to August 2015. We calculated the positive predictive value (PPV) of ultrasonography, taking renal scintigraphy and pathology as the gold standard. We calculated a survival curve according to the Kaplan-Meier method to assess the annual probability of spontaneous resolution of the multicystic kidney. RESULTS: Fifty six patients were identified, 48 (85.7%) of whom had a prenatal diagnosis. Thirty eight (67.9%) of the patients were males, and the left side was affected in 33 (58.9%) of the patients. We observed associated urological abnormalities in 22 (39.29%) patients, with vesicoureteral reflux the most common (8, 14.29%). Seven patients (12.5%) developed renal failure. Forty-nine (87.5%) patients developed compensatory contralateral renal hypertrophy. Of the 33 patients who underwent surgery, the pathology results confirmed the MCDK diagnosis in 32. Compared with scintigraphy and pathology, the PPV of ultrasonography was 100% and 97%, respectively. The rate of spontaneous involution was 5.4% at 3 months of life, 11.3% at 2 years and 38.4% at 5 years. CONCLUSIONS: In our experience, the conservative treatment of MCDK, until at least 5 years of age, is safe. Our data suggest that performing scintigraphy is not required for these patients, which means lower radiation exposure, as well as financial savings. PMID- 27666955 TI - Study of the effect of ceramic Ta2O5 nanoparticle distribution on cellular dose enhancement in a kilovoltage photon field. AB - The application of nanoparticles (NPs) in radiotherapy is an increasingly attractive technique to improve clinical outcomes. The internalisation of NPs within the tumour cells enables an increased radiation dose to critical cellular structures. The purpose of this study is to investigate, by means of Geant4 simulations, the dose enhancement within a cell population irradiated with a 150kVp photon field in the presence of a varying concentration of tantalum pentoxide (Ta2O5) NP aggregates, experimentally observed to form shells within tumour cells. This scenario is compared to the more traditionally simulated homogeneous solution of NP material in water with the same weight fraction of Ta2O5, as well as to a cell population without NPs present. The production of secondary electrons is enhanced by increased photoelectric effect interactions within the high-Z material and this is examined in terms of their kinetic energy spectra and linear energy transfer (LET) with various NP distributions compared to water. Our results indicate that the shell formation scenario limits the dose enhancement at 150kVp. The underlying mechanism for this limit is discussed. PMID- 27666956 TI - Sphingobacterium cibi sp. nov., isolated from the food-waste compost and emended descriptions of Sphingobacterium spiritivorum (Holmes et al. 1982) Yabuuchi et al. 1983 and Sphingobacteriumthermophilum Yabe et al. 2013. AB - A novel, pale yellow-coloured, Gram-staining-negative, aerobic, rod-shaped and non-motile bacterium, designated as strain CC-YY411T, was isolated from the food waste compost and subjected to polyphasic taxonomy. Strain CC-YY411T exhibited the highest pairwise 16S rRNA gene sequence similarity to Sphingobacterium thermophilum JCM 17858T (94.6 %) while sharing 94.1 to 89.7 % similarities with other Sphingobacterium species. Novel strain established a discrete phylogenetic lineage within the clade that accommodated validly established members of the genus Sphingobacterium. The polar lipid profile of strain CC-YY411T contained major amounts of phosphatidylethanolamine, one unidentified lipid and two unidentified aminolipids besides accommodating trace amounts of a sphingolipid, two phospholipids, an unidentified aminophospholipid and an unidentified glycolipid. The DNA G+C content of strain CC-YY411T was 34.5 mol%. The major and minor respiratory quinones were MK-7 (89.1 %) and MK-6 (10.9 %), respectively. The predominant fatty acids were iso-C15 : 0 (24.0 %), iso-C17 : 0 3-OH (11.9 %), iso-C15 : 0 3-OH (6.9 %), C15 : 1omega5c (5.5 %) and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) (32.0 %). Based on the phylogenetic, phenotypic and chemotaxonomic distinctiveness, strain CC-YY411T represents a novel species of Sphingobacterium, for which the name Sphingobacteriumcibi sp. nov. is proposed. The type strain is CC-YY411T (=BCRC 80430T=JCM 18407T). Amended species descriptions of Sphingobacterium spiritivorum(Holmes et al. 1982) Yabuuchi et al. 1983 and Sphingobacterium thermophilum Yabe et al. 2013 are also proposed based on new data obtained in this study. PMID- 27666957 TI - F-actin rearrangement is regulated by mTORC2/Akt/Girdin in mouse fertilized eggs. AB - : In mouse fertilized eggs, correct assembly and distribution of the actin cytoskeleton are intimately related to cleavage in early-stage embryos. However, in mouse fertilized eggs, mechanisms and involved factors responsible for regulating the actin cytoskeleton are poorly defined. In this study, mTORC2, PKB/Akt and Girdin were found to modulate division of mouse fertilized eggs by regulating distribution of the actin cytoskeleton. RNA interference (RNAi) mediated depletion of mTORC2, Akt1 or Girdin disrupted F-actin rearrangement and strongly inhibited egg development. PKB/Akt has been proven to be a downstream target of the mTORC2 signalling pathway. Girdin, a newly found actin cross linker, has been proven to be a downstream target of the Akt signalling pathway. Furthermore, phosphorylation of both Akt1 and girdin was affected by knockdown of mTORC2. Akt1 positively regulated development of the mouse fertilized eggs by girdin-mediated F-actin rearrangement. Thus it seems that girdin could be a downstream target of the Akt1-mediated signalling pathway. Collectively, this study aimed to prove participation of mTORC2/Akt in F-actin assembly in early stage cleavage of mouse fertilized eggs via the function of girdin. OBJECTIVES: In mouse fertilized eggs, the proper assembly and distribution of actin cytoskeleton is intimately related with the cleavage of early-stage embryo. However, in mammals, especially in mouse fertilized eggs, the mechanisms and involved factors responsible for regulating the actin cytoskeleton are poorly defined. The aim of this study was to determine the role of mTORC2,PKB/Akt and Girdin in early development of fertilized mouse eggs, via regulating the distribution of actin cytoskeleton. MATERIALS AND METHODS: Changes of F-actin after treatting with mTORC2 shRNA, Akt siRNA or Girdin siRNA were observed by Immunofluorescence staining and laser-scanning confocal microscopy. Levels of phosphorylated Girdin at Se1417 were detected by Western immunoblotting. Percentages of cells undergoing division were determined by counting, using a dissecting microscope. RESULTS: RNA interference (RNAi)-mediated depletion of mTORC2, Akt1 or Girdin disrupts F-actin rearrangement, and remarkably inhibited the development of mouse-fertilized eggs. PKB/Akt has been proved to be a downstream target of the mTORC2 signaling pathway. Girdin, the newly found actin cross linker, has been proved to be a downstream target of the Akt signaling pathway. Furthermore phosphorylation of both Akt1 and Girdin were affected by knockdown of mTORC2. Akt1 positively regulates the development of mouse fertilized eggs by Girdin mediated F-actin rearrangement. Girdin could be a downstream target of the Akt1-mediated signaling pathway. CONCLUSIONS: Collectively, this study aimed to prove the participation of mTORC2/Akt in F actin assembling in early-stage cleavage of mouse fertilized eggs via the function of Girdin. PMID- 27666958 TI - Exercise as an Adjunctive Treatment for Substance Use Disorders: Rationale and Intervention Description. AB - Substance use disorders (SUDs) are maladaptive patterns of substance use that are associated with psychiatric comorbidity, unhealthy lifestyle choices, and high rates of relapse. Exercise is associated with a wide range of acute and long-term benefits for both mental and physical health and is presently being investigated as a promising adjunctive treatment for SUD. Despite positive effects of regular physical activity on treatment outcomes and risk factors for relapse, low adherence and high attrition rates limit the benefits derived from exercise interventions. Lack of motivation is one of many perceived barriers to initiating exercise that contributes to poor adherence to interventions. In the present article, we describe the protocol for a novel, integrated exercise intervention that combines motivational interviewing (MI), a client-centered approach designed to enhance intrinsic motivation and resolve ambivalence toward change, and contingency management (CM), a behavioral treatment that provides monetary incentives for the completion of target behaviors. The protocol seeks to address the challenges surrounding initiation and maintenance of an exercise program at a level consistent with public health guidelines, particularly for sedentary patients. We conclude with considerations for the implementation of the intervention in SUD specific clinics. PMID- 27666959 TI - Recombinant Leishmania Rab6 (rLdRab6) is recognized by sera from visceral leishmaniasis patients. AB - Rab proteins form the largest branch of the Ras superfamily. Rab proteins are key regulators of intracellular vesicular transport and membrane trafficking. Although RabGTPases are well-recognized targets in human diseases but are under explored therapeutically in the Leishmania parasite. Using a quantitative cytofluorimetric assay, we analyzed the composition and organization of Rab6GTPase protein which was found to be primarily localized on the parasite subpellicular membrane and flagellum due to its association with kinesin motor proteins in the cytoskeletal microtubules. Our aim was to also assess the diagnostic role of recombinant Rab6 protein from Leishmania donovani (rLdRab6) using sera/plasma of Indian visceral leishmaniasis (VL) patients. Receiver operating characteristic (ROC) curve analysis indicated 100% sensitivity and 100% specificity for rLdRab6-based ELISA which was almost similar in comparison to recombinant K39-based ELISA (95.83% sensitivity and 100% specificity). Sera of patients from another intracellular pathogenic infection, Mycobacterium tuberculosis, did not contain any significant levels of anti-rLdRab6 antibody. Thus rLdRab6 accuracy in visceral leishmaniasis diagnosis makes it a promising antigen for clinical use. PMID- 27666961 TI - CKIP-1 knockout offsets osteoporosis induced by simulated microgravity. AB - Casein kinase 2-interacting protein 1 (CKIP-1) is a negative regulator for bone formation. CKIP-1 knockout (KO) mice are very important for research on countermeasures to bone loss induced by space microgravity. Under simulated microgravity, the bone metabolism of CKIP-1 KO mice was different than that of wild-type (WT) mice. Many experiments all showed that the KO mice had significantly enhanced ossification in the tail suspension conditions, and the differences were closely related to the time the mice were exposed to the microgravity environment. Our results reveal the effect of CKIP-1 on the regulation of bone metabolism and osteogenesis in vivo and the ability of this gene to offset osteoporosis, and they suggest an approach to the treatment of osteoporosis induced by microgravity in space. PMID- 27666960 TI - Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression. AB - Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective effects of XBJ in a rat model of D-galactosamine (D-Gal)- and lipopolysaccharide (LPS)-induced acute liver injury. In the present study, the rats were injected with D-Gal and LPS intraperitoneally to induce acute liver injury. Two hours prior to D-Gal and LPS administration, the treatment group was administered XBJ by intravenous infusion. The effects of XBJ on D-Gal- and LPS induced expression of tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2), nuclear factor-kappaB (NF-kappaB), matrix metalloproteinase-9 (MMP-9) and heme oxygenase-1 (HO-1) as well as mitogen-activated protein kinase (MAPK) signaling was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis, immunofluorescence, as well as by analysing the serum levels of pro-inflammatory cytokines and the transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the rat liver tissues were also measured. For histological analysis, hematoxylin and eosin (H&E)-stained liver samples were evaluated. The results showed that XBJ upregulated TIPE2 and HO-1 expression, reduced the expression of NF-kappaB65 and MMP-9, inhibited the LPS-induced gene expression of c-jun N terminal kinase (JNK) and p38 MAPK, decreased the generation of pro-inflammatory cytokines [interleukin (IL)-6, IL-13 and TNF-alpha], inhibited ALT and AST activity, and ameliorated D-Gal- and LPS-induced liver injury. The histological results also demonstrated that XBJ attenuated D-Gal- and LPS-induced liver inflammation. It was found that XBJ may prevent LPS-induced pro-inflammatory gene expression through inhibiting the NF-kappaB and MAPK signaling pathways by upregulating TIPE2 expression, thereby attenuating LPS-induced liver injury in rats. The marked protective effects of XBJ suggest that it has the potential to be used in the treatment of LPS-induced liver injury. PMID- 27666962 TI - A review of resolution measures and related aspects in 3D Electron Microscopy. AB - Fourier Shell Correlation, Spectral Signal-to-Noise Ratio, Fourier Neighbour Correlation, and Differential Phase Residual are different measures that have been proposed over time to determine the spatial resolution achieved by a certain 3D reconstruction. Estimates of B-factors to describe the reduction in signal-to noise ratio with increasing resolution is also a useful parameter. All these concepts are interrelated and different thresholds have been given for each one of them. However, the problem of resolution assessment in 3DEM is still far from settled and preferences are normally adopted in order to choose the "correct" threshold. In this paper we review the different concepts, their theoretical foundations and the derivation of their statistical distributions (the basis for establishing sensible thresholds). We provide theoretical justifications for some common practices in the field for which a formal justification was missing. We also analyze the relationship between SSNR and B-factors, the electron dose needed for achieving a given contrast and resolution, the number of images required, etc. Finally, we review the consequences for the number of particles needed to achieve a certain resolution and how to analyze the Signal-to-Noise Ratio for a sequence of imaging operations. PMID- 27666963 TI - Chronic cholestasis in a patient with sickle-cell anemia: Histological findings. PMID- 27666964 TI - lncRNA-SNHG7 promotes the proliferation, migration and invasion and inhibits apoptosis of lung cancer cells by enhancing the FAIM2 expression. AB - There is growing evidence that long non-coding RNAs (lncRNAs) are related to cancer development. In the present study, we found that the expression levels of lncRNA-SNHG7 mRNA and protein obviously increased in lung cancer tissues compared to adjacent non-cancerous tissues. Simultaneously, the expression levels of Fas apoptotic inhibitory molecule 2 (FAIM2) also increased in lung cancer tissues. In addition, lncRNA-SNHG7 was of positive relevance with FAIM2 in human lung cancer tissues. Silence of lncRNA-SNHG7 by siRNA repressed the level of FAIM2 protein and suppressed cell proliferation, migration and invasion and accelerated apoptosis of A594 cells in vitro. Furthermore, silence of FAIM2 by siRNA generated a phenotype similar to silence of lncRNA-SNHG7 by siRNA. Therefore, our research showed that lncRNA-SNHG7 promotes the proliferation, migration and invasion, and inhibits apoptosis of lung cancer cells by enhancing the FAIM2 expression, suggesting that lncRNA-SNHG7 as a key regulator of gene expression, may be a promising therapeutic strategy for the treatment of lung cancer. It may improve the understanding of their biogenesis and function of lung cancer and further provide the theoretical fundamental basis for cancer pathogenesis and treatment. PMID- 27666965 TI - The Earliest Stages of Mitochondrial Adaptation to Low Oxygen Revealed in a Novel Rhizarian. AB - Mitochondria exist on a functional and evolutionary continuum that includes anaerobic mitochondrion-related organelles (MROs), such as hydrogenosomes. Hydrogenosomes lack many classical mitochondrial features, including conspicuous cristae, mtDNA, the tricarboxylic acid (TCA) cycle, and ATP synthesis powered by an electron transport chain (ETC); instead, they produce ATP anaerobically, liberating H2 and CO2 gas in the process. However, our understanding of the evolutionary transformation from aerobic mitochondria to various MRO types remains incomplete. Here we describe a novel MRO from a cercomonad (Brevimastigomonas motovehiculus n. sp.; Rhizaria). We have sequenced its 30,608 bp mtDNA and characterized organelle function through a combination of transcriptomic, genomic, and cell biological approaches. B. motovehiculus MROs are metabolically versatile, retaining mitochondrial metabolic pathways, such as a TCA cycle and ETC-driven ATP synthesis, but also possessing hydrogenosomal-type pyruvate metabolism and substrate-level phosphorylation. Notably, the B. motovehiculus ETC is degenerate and appears to be losing cytochrome-based electron transport (complexes III and IV). Furthermore, the F1Fo ATP synthase (complex V) is unique, with the highly conserved Atpalpha subunit fragmented into four separate pieces. The B. motovehiculus MRO appears to be in the process of losing aerobic metabolic capacities. Our findings shed light on the transition between organelle types, specifically the early stages of mitochondrial adaptation to anaerobiosis. PMID- 27666966 TI - Kinematic Diversity in Rorqual Whale Feeding Mechanisms. AB - Rorqual whales exhibit an extreme lunge filter-feeding strategy characterized by acceleration to high speed and engulfment of a large volume of prey-laden water [1-4]. Although tagging studies have quantified the kinematics of lunge feeding, the timing of engulfment relative to body acceleration has been modeled conflictingly because it could never be directly measured [5-7]. The temporal coordination of these processes has a major impact on the hydrodynamics and energetics of this high-cost feeding strategy [5-9]. If engulfment and body acceleration are temporally distinct, the overall cost of this dynamic feeding event would be minimized. However, greater temporal overlap of these two phases would theoretically result in higher drag and greater energetic costs. To address this discrepancy, we used animal-borne synchronized video and 3D movement sensors to quantify the kinematics of both the skull and body during feeding events. Krill-feeding blue and humpback whales exhibited temporally distinct acceleration and engulfment phases, with humpback whales reaching maximum gape earlier than blue whales. In these whales, engulfment coincided largely with body deceleration; however, humpback whales pursuing more agile fish demonstrated highly variable coordination of skull and body kinematics in the context of complex prey-herding techniques. These data suggest that rorquals modulate the coordination of acceleration and engulfment to optimize foraging efficiency by minimizing locomotor costs and maximizing prey capture. Moreover, this newfound kinematic diversity observed among rorquals indicates that the energetic efficiency of foraging is driven both by the whale's engulfment capacity and the comparative locomotor capabilities of predator and prey. VIDEO ABSTRACT. PMID- 27666968 TI - The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories. AB - Our day-to-day experiences are often similar to one another, occurring in the same place at the same time of day, with common people and objects, and with a shared purpose. Humans have an episodic memory to represent unique, personal events that are rich in detail [1]. For this to occur, at least two basic neural mechanisms are required: one to orthogonalize or "separate" overlapping input patterns at encoding and another to reinstate or "complete" memories from partial cues at retrieval [2-6]. To what extent do these purported "pattern separation" and "pattern completion" mechanisms rely on distinct subfields of the hippocampus [6]? Computational models [4-6] and lesion and genetic studies in rodents [7-12] largely point to the dentate gyrus as responsible for pattern separation and the CA3 and CA1 subfields for pattern completion (but see [13-16]). In high resolution fMRI studies of humans, behavioral discrimination and completion tasks designed to approximate pattern separation and pattern completion, respectively, elicit the predicted pattern of activity in the dentate gyrus and CA3/CA1 [17 21]. Likewise, impaired behavioral discrimination has been demonstrated in individuals with hippocampal lesions [22, 23], but the lesions most likely encompass other subfields. Examination of these processes in individuals with selective lesions to hippocampal subfields is needed to infer causation [19]. Here, we report the rare case of BL, a 54-year-old man with bilateral ischemic lesions to the hippocampus [24] primarily affecting the dentate gyrus. Studying BL provides the unique opportunity to directly evaluate theories of hippocampal function that assign the dentate gyrus a specific role in discriminating old from new memories. PMID- 27666967 TI - Fascin- and alpha-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting. AB - Cells assemble and maintain functionally distinct actin cytoskeleton networks with various actin filament organizations and dynamics through the coordinated action of different sets of actin-binding proteins. The biochemical and functional properties of diverse actin-binding proteins, both alone and in combination, have been increasingly well studied. Conversely, how different sets of actin-binding proteins properly sort to distinct actin filament networks in the first place is not nearly as well understood. Actin-binding protein sorting is critical for the self-organization of diverse dynamic actin cytoskeleton networks within a common cytoplasm. Using in vitro reconstitution techniques including biomimetic assays and single-molecule multi-color total internal reflection fluorescence microscopy, we discovered that sorting of the prominent actin-bundling proteins fascin and alpha-actinin to distinct networks is an intrinsic behavior, free of complicated cellular signaling cascades. When mixed, fascin and alpha-actinin mutually exclude each other by promoting their own recruitment and inhibiting recruitment of the other, resulting in the formation of distinct fascin- or alpha-actinin-bundled domains. Subdiffraction-resolution light microscopy and negative-staining electron microscopy revealed that fascin domains are densely packed, whereas alpha-actinin domains consist of widely spaced parallel actin filaments. Importantly, other actin-binding proteins such as fimbrin and espin show high specificity between these two bundle types within the same reaction. Here we directly observe that fascin and alpha-actinin intrinsically segregate to discrete bundled domains that are specifically recognized by other actin-binding proteins. PMID- 27666969 TI - Myosin-7b Promotes Distal Tip Localization of the Intermicrovillar Adhesion Complex. AB - Transporting epithelial cells interact with the luminal environment using a tightly packed array of microvilli known as the brush border. During intestinal epithelial differentiation, microvillar packing and organization are driven by cadherin-dependent adhesion complexes that localize to the distal tips of microvilli, where they drive physical interactions between neighboring protrusions. Although enrichment of the "intermicrovillar adhesion complex" (IMAC) at distal tips is required for proper function, the mechanism driving tip accumulation of these factors remains unclear. Here, we report that the actin based motor myosin-7b (Myo7b) promotes the accumulation of IMAC components at microvillar tips. Myo7b is highly enriched at the tips of microvilli in both kidney and intestinal brush borders, and loss of Myo7b in differentiating intestinal epithelial cells disrupts intermicrovillar adhesion and, thus, brush border assembly. Analysis of cells lacking Myo7b revealed that IMAC components and the resulting intermicrovillar adhesion links are mislocalized along the microvillar axis rather than enriched at the distal tips. We also found that Myo7b motor domains are capable of supporting tip-directed transport. However, motor activity is supplemented by other passive targeting mechanisms that together drive highly efficient IMAC accumulation at the tips. These findings illuminate the molecular basis of IMAC enrichment at microvillar tips and hold important implications for understanding apical morphogenesis in transporting and sensory epithelial tissues. PMID- 27666970 TI - Seeing the Errors You Feel Enhances Locomotor Performance but Not Learning. AB - In human motor learning, it is thought that the more information we have about our errors, the faster we learn. Here, we show that additional error information can lead to improved motor performance without any concomitant improvement in learning. We studied split-belt treadmill walking that drives people to learn a new gait pattern using sensory prediction errors detected by proprioceptive feedback. When we also provided visual error feedback, participants acquired the new walking pattern far more rapidly and showed accelerated restoration of the normal walking pattern during washout. However, when the visual error feedback was removed during either learning or washout, errors reappeared with performance immediately returning to the level expected based on proprioceptive learning alone. These findings support a model with two mechanisms: a dual-rate adaptation process that learns invariantly from sensory prediction error detected by proprioception and a visual-feedback-dependent process that monitors learning and corrects residual errors but shows no learning itself. We show that our voluntary correction model accurately predicted behavior in multiple situations where visual feedback was used to change acquisition of new walking patterns while the underlying learning was unaffected. The computational and behavioral framework proposed here suggests that parallel learning and error correction systems allow us to rapidly satisfy task demands without necessarily committing to learning, as the relative permanence of learning may be inappropriate or inefficient when facing environments that are liable to change. PMID- 27666972 TI - "Singing" Fish Rely on Circadian Rhythm and Melatonin for the Timing of Nocturnal Courtship Vocalization. AB - The patterning of social acoustic signaling at multiple timescales, from day night rhythms to acoustic temporal properties, enhances sender-receiver coupling and reproductive success [1-8]. In diurnal birds, the nocturnal production of melatonin, considered the major vertebrate timekeeping hormone [9, 10], suppresses vocal activity but increases song syllable duration over circadian and millisecond timescales, respectively [11, 12]. Comparable studies are lacking for nocturnal vertebrates, including many teleost fish species that are also highly vocal during periods of reproduction [4, 13-20]. Utilizing continuous sound recordings, light cycle manipulations, hormone implants, and in situ hybridization, we demonstrate in a nocturnally breeding teleost fish that (1) courtship vocalization exhibits an endogenous circadian rhythm under constant dark conditions that is suppressed under constant light, (2) exogenous delivery of a melatonin analog under inhibitory constant light conditions rescues courtship vocal activity as well as the duration of single calls, and (3) melatonin receptor 1b is highly expressed in evolutionarily conserved neuroendocrine and vocal-acoustic networks crucial for patterning reproductive and vocal behaviors in fishes and tetrapods. Our findings, together with those in birds, show melatonin's remarkable versatility as a timing signal in distantly related lineages. It exerts opposing effects on vocalization in nocturnal versus diurnal species at the circadian timescale but comparable effects at the finer timescale of acoustic features. We propose that melatonin's separable effects at different timescales depends on its actions within distinct neural networks that control circadian rhythms, reproduction, and vocalization, which may be selected upon over evolutionary time as dissociable modules to pattern and coordinate social behaviors. VIDEO ABSTRACT. PMID- 27666971 TI - A Dome-Headed Stem Archosaur Exemplifies Convergence among Dinosaurs and Their Distant Relatives. AB - Similarities in body plan evolution, such as wings in pterosaurs, birds, and bats or limblessness in snakes and amphisbaenians, can be recognized as classical examples of convergence among animals [1-3]. We introduce a new Triassic stem archosaur that is unexpectedly and remarkably convergent with the "dome-headed" pachycephalosaur dinosaurs that lived over 100 million years later. Surprisingly, numerous additional taxa in the same assemblage (the Otis Chalk assemblage from the Dockum Group of Texas) demonstrate the early acquisition of morphological novelties that were later convergently evolved by post-Triassic dinosaurs. As one of the most successful clades of terrestrial vertebrates, dinosaurs came to occupy an extensive morphospace throughout their diversification in the Mesozoic Era [4, 5], but their distant relatives were first to evolve many of those "dinosaurian" body plans in the Triassic Period [6-8]. Our analysis of convergence between archosauromorphs from the Triassic Period and post-Triassic archosaurs demonstrates the early and extensive exploration of morphospace captured in a single Late Triassic assemblage, and we hypothesize that many of the "novel" morphotypes interpreted to occur among archosaurs later in the Mesozoic already were in place during the initial Triassic archosauromorph, largely non-dinosaurian, radiation and only later convergently evolved in diverse dinosaurian lineages. PMID- 27666973 TI - Effects of early adolescent methamphetamine exposure on anxiety-like behavior and corticosterone levels in mice. AB - Methamphetamine (MA) is an addictive psychomotor stimulant that affects the central nervous system and alters behavior. The effects of MA are modulated by age, and while much research has examined the effects of MA use in adults, relatively little research has examined the effects in adolescents. As the brain is developing during adolescence, it is important that we understand the effects of MA exposure in adolescence. This research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test and plasma corticosterone levels in adolescent male C57BL/6J mice. Baseline locomotor and anxiety-like behaviors were assessed in the open field test. Immediately following baseline measurements, mice were exposed to saline or 4mg/kg MA and locomotor and anxiety-like behavior were measured. Serum was collected immediately after testing and plasma corticosterone levels measured. There were no group differences in baseline behavioral measurements. MA-exposed adolescent mice showed increased locomotor activity and anxiety-like behavior in the open field compared with saline controls. There was no effect of MA on plasma corticosterone levels. These data suggest that acute MA exposure during adolescence increases locomotor activity and anxiety-like behavior, but does not alter plasma corticosterone levels. PMID- 27666975 TI - An approach to EEG-based emotion recognition using combined feature extraction method. AB - EEG signal has been widely used in emotion recognition. However, too many channels and extracted features are used in the current EEG-based emotion recognition methods, which lead to the complexity of these methods This paper studies on feature extraction on EEG-based emotion recognition model to overcome those disadvantages, and proposes an emotion recognition method based on empirical mode decomposition (EMD) and sample entropy. The proposed method first employs EMD strategy to decompose EEG signals only containing two channels into a series of intrinsic mode functions (IMFs). The first 4 IMFs are selected to calculate corresponding sample entropies and then to form feature vectors. These vectors are fed into support vector machine classifier for training and testing. The average accuracy of the proposed method is 94.98% for binary-class tasks and the best accuracy achieves 93.20% for the multi-class task on DEAP database, respectively. The results indicate that the proposed method is more suitable for emotion recognition than several methods of comparison. PMID- 27666974 TI - Photobiomodulation by laser therapy rescued auditory neuropathy induced by ouabain. AB - Auditory neuropathy is a hearing disorder caused by impaired auditory nerve function. The lack of information about the pathophysiology of this disease limits early diagnosis and further treatment. Laser therapy is a novel approach to enhance nerve growth or induce axonal regeneration. We induced auditory neural degeneration sparing the sensory epithelium with local ouabain application in an animal model and observed the rescue effect of photobiomodulation (PBM), showing recovered auditory function and favorable histologic outcome. Hearing was evaluated using the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Seven days after ouabain application, the animals were sacrificed to evaluate the morphological changes. DPOAE change was not observed in all groups after ouabain application indicating no changes of outer hair cell function. Ouabain application increased the ABR thresholds increase, while the use of ouabain plus laser produced lower threshold compared to the ouabain group. Hematoxylin and Eosin staining of cochlea mid-modiolar sections in animals treated with ouabain showed damaged spiral ganglion cells, neurofilaments, and post synaptic puncta. Ouabain plus laser group showed higher number of spiral ganglion cells, higher density of neurofilaments, and higher number post synaptic puncta counts compared with ouabain application group. Short term application of ouabain caused spiral ganglion cell damage while sparing the inner and outer hair cells in gerbils. Photobiomodulation alleviated the hearing loss caused by ouabain induced auditory neuropathy. The results indicate the possible role of photobiomodulation therapy for inner ear diseases accompanied by spiral ganglion degeneration. PMID- 27666976 TI - Levodopa enhances immobility induced by spinal cord electromagnetic stimulation in rats. AB - BACKGROUND: The repetitive ElectroMagnetic Stimulation (rEMS) is an innocuous method applied to modulate neurocircuits in real-time to study the physiology of the central nervous system and treat neuropsychiatric conditions. Preliminary data suggest that spinal rEMS induces behavioral changes in awake rats. However, the mechanisms behind this phenomenon remain largely unknown. METHODS: Twenty five male Wistar rats were divided into five subgroups of five animals each: one subgroup was drug-free, two subgroups received Levodopa+Benserazide 250+25mg/kg for two or seven days, and the remaining two subgroups received Haloperidol 0.1 or 0.3mg/kg for two days. The animals were restrained during sham rEMS (day 1) followed by real rEMS of the cervicothoracic region at a different day (day 2 or 7, depending on subgroup). Four behavioral parameters were quantified: Walking, Climbing, Grooming, and Cornering. RESULTS: rEMS reduced Walking and increased Cornering duration when applied over the cervicothoracic region of drug-free animals. A pretreatment with Levodopa+Benserazide for two or seven days induced an additional decrease in Walking after rEMS. This reduction was maximum after the treatment for seven days and associated with extinction of Climbing and increase in Cornering. A pretreatment with Haloperidol 0.1mg/kg reduced Grooming after rEMS, but did not prevent the reduction in Walking. CONCLUSIONS: Cervicothoracic rEMS induced complex immobility responses that are in part modulated by dopaminergic pathways in rats. Further studies are necessary to determine the specific mechanisms involved. PMID- 27666977 TI - Aerobic exercise abolishes cTBS-induced suppression of motor cortical excitability. AB - A preceding bout of acute aerobic exercise can enhance the induction of early long-term potentiation (LTP) in the primary motor cortex (M1). However, the influence of exercise when performed after the induction of plasticity has not been investigated. In addition, it is unclear whether the same effects are seen with techniques that induce long-term depression (LTD). We used continuous theta burst stimulation (cTBS) to temporarily suppress cortical excitability and investigate whether moderate-intensity cycling exercise would alter the duration or intensity of cTBS after-effects in a nonexercised upper limb muscle. We observed that cTBS effects were abolished when followed by exercise, with no corresponding changes in intracortical network activity. We hypothesize that the induction of LTD may be suppressed by exercise-linked neurotransmitters that interact with glutamate receptors. Exercise appears to shift the neural balance towards facilitation and may work to counteract the effects of LTD-like processes. PMID- 27666978 TI - Transplantation of bone marrow mononuclear cells prolongs survival, delays disease onset and progression and mitigates neuronal loss in pre-symptomatic, but not symptomatic ALS mice. AB - Cell-based therapy provides a novel strategy to restore lost neurons or modulate the degenerating microenvironment in amyotrophic lateral sclerosis (ALS). This study verified the therapeutic potential of bone marrow mononuclear cells (BMMCs) in SOD1G93A mice. BMMCs were obtained from enhanced green fluorescent protein (EGFP) transgenic C57BL/6 mice (EGFPBMMCs) or from SOD1G93A transgenic mice (mSOD1BMMCs) and given to mice at the pre-symptomatic or late symptomatic stage. Survival, body weight and motor performance data were recorded. DNA integrity was evaluated using the alkaline comet assay. The spinal cords were collected to assess motoneuron preservation and cell migration. EGFPBMMCs and mSOD1BMMCs transplantation to pre-symptomatic SOD1G93A mice prolonged survival and delayed disease progression. The effects were more significant for the EGFPBMMC transplanted mice. In late symptomatic mice, EGFPBMMCs promoted a discrete increase in survival, without other clinical improvements. DNA from EGFPBMMCs and mSOD1BMMCs was found in the spinal cords of transplanted animals. DNA damage was not modified by BMMCs in any of the studied groups. Despite positive behavioral effects observed in our study, the limited results we observed for late transplanted mice call for caution before clinical application of BMMCs in ALS. PMID- 27666979 TI - Postoperative ileus: Pathophysiology, incidence, and prevention. AB - Postoperative ileus (POI) is a major focus of concern for surgeons because it increases duration of hospitalization, cost of care, and postoperative morbidity. The definition of POI is relatively consensual albeit with a variable definition of interval to resolution ranging from 2 to 7 days for different authors. This variation, however, leads to non-reproducibility of studies and difficulties in interpreting the results. Certain risk factors for POI, such as male gender, advanced age and major blood loss, have been repeatedly described in the literature. Understanding of the pathophysiology of POI has helped combat and prevent its occurrence. But despite preventive and therapeutic efforts arising from such knowledge, 10 to 30% of patients still develop POI after abdominal surgery. In France, pharmacological prevention is limited by the unavailability of effective drugs. Perioperative nutrition is very important, as well as limitation of preoperative fasting to 6 hours for solid food and 2 hours for liquids, and virtually no fasting in the postoperative period. Coffee and chewing gum also play a preventive role for POI. The advent of laparoscopy has led to a significant improvement in the recovery of gastrointestinal function. Enhanced recovery programs, grouping together all measures for prevention or cure of POI by addressing the mechanisms of POI, has reduced the duration of hospitalization, morbidity and interval to resumption of transit. PMID- 27666980 TI - Characterization of Dye Decolorization in Cell-Free Culture Broth of Trametes versicolor CBR43. AB - The dye decolorization rate in a cell-free culture broth of the white-rot fungus Trametes versicolor CBR43 was studied, including the effects of inhibitors of NaCl, Zn(II), and Cd(II) on dye decolorization activity. The maximum rates of dye decolorization in cell-free culture broth were 1,410, 44.7, 41.2, and 0.19 MUmol.l-1.min-1 for Acid Blue 62, Acid Black 175, Reactive Blue 4, and Acid Red 114, respectively. The inhibition effects of NaCl, Zn(II), and Cd(II) on dye decolorization were quantitatively compared using the half maximal inhibition concentration (IC50), which indicates the concentration of an inhibitor required for 50% inhibition. Based on IC50 values, dye decolorization in the cell-free culture broth of CBR43 was most potently inhibited by Cd(II), whereas the inhibitory effect of NaCl was relatively low. The dye decolorization rates and IC50 data can be used in the design and development of a dyewastewater treatment process using T. versicolor CBR43 and its operating factors. PMID- 27666981 TI - Proteomic Analysis of Shigella Virulence Effectors Secreted under Different Conditions. AB - A series of novel effector molecules secreted by the type three secretion system (T3SS) of Shigella spp. have been reported in recent years. In this study, a proteomic approach was applied to study T3SS effectors systematically. First, proteins secreted by theS. flexneri wild-type strain after Congo Red induction were separated and identified using two-dimensional electrophoresis to display the relative abundance of all kinds of early effectors for the first time. Then, a gene deletion mutant of known virulence repressor (OspD1) and a gene overexpressed mutant of two known virulence activators (MxiE and IpgC) were constructed and analyzed to discover potential late effectors. Furthermore, the supernatant proteins of gene deletion mutants of two known translocators (IpaB and IpaD), which would constantly secrete effectors, were also analyzed. Among all of the secreted proteins identified in our study, IpaH1.4, IpaH_5, and IpaH_7 have not been reported before. These proteomics data of the secreted effectors will be valuable to understand the pathogenesis of S. flexneri. PMID- 27666982 TI - Selection of Potential Virulence Factors Contributing to Streptococcus suis Serotype 2 Penetration into the Blood-Brain Barrier in an In Vitro Co-Culture Model. AB - Meningitis caused by Streptococcus suis serotype 2 (S. suis 2) is a great threat to the pig industry and human health. Virulence factors associated with the pathogenesis of meningitis have yet to be clearly defined, even though many potential S. suis 2 virulence factors have been identified. This greatly hinders the progress of S. suis 2 meningitis pathogenesis research. In this study, a co culture blood-brain barrier (BBB) model was established using primary porcine brain microvascular endothelial cells and astrocytes, and the whole genome library of S. suis 2 was constructed using phage display technology. Finally, a total of 14 potential virulence factors contributing to S. suis 2 adherence to and invasion of the BBB were selected by analyzing the interactions between the phage library and the co-culture model. Twelve of these factors have not been previously reported in meningitis-related research. The data provide valuable insight into the pathogenesis of S. suis 2 meningitis and potential targets for the development of drug therapies. PMID- 27666983 TI - Sclareol Protects Staphylococcus aureus-Induced Lung Cell Injury via Inhibiting Alpha-Hemolysin Expression. AB - Staphylococcus aureus (S. aureus) is a common gram-positive bacterium that causes serious infections in humans and animals. With the continuous emergence of methicillin-resistant S. aureus (MRSA) strains, antibiotics have limited efficacy in treating MRSA infections. Accordingly, novel agents that act on new targets are desperately needed to combat these infections. S. aureus alpha-hemolysin plays an indispensable role in its pathogenicity. In this study, we demonstrate that sclareol, a fragrant chemical compound found in clary sage, can prominently decrease alpha-hemolysin secretion in S. aureus strain USA300 at sub-inhibitory concentrations. Hemolysis assays, western-blotting, and RT-PCR were used to detect the production of alpha-hemolysin in the culture supernatant. When USA300 was co-cultured with A549 epithelial cells, sclareol could protect the A549 cells at a final concentration of 8 MUg/ml. The protective capability of sclareol against the USA300-mediated injury of A549 cells was further shown by cytotoxicity assays and live/dead analysis. In conclusion, sclareol was shown to inhibit the production of S. aureus alpha-hemolysin. Sclareol has potential for development as a new agent to treat S. aureus infections. PMID- 27666985 TI - One-Step Purification of Melittin Derived from Apis mellifera Bee Venom. AB - The concern over the use of melittin in honey bee venom due to its adverse reaction caused by allergens such as phospholipase A2 (PLA2) and hyaluronidase (HYA) has been an obstacle towards its usage. We developed a novel single-step method for melittin purification and the removal of PLA2 and HYA. This study explores the influence of pH, buffer compositions, salt concentration, and types of cation-exchange chromatography resins on the recovery of melittin and the removal of both HYA and PLA2. Melittin was readily purified with a strong cation exchange resin at pH 6.0 with sodium phosphate buffer. It resulted in a recovery yield of melittin up to 93% (5.87 mg from a total of 6.32 mg of initial melittin in crude bee venom), which is higher than any previously reported studies on melittin purification. PLA2 (99%) and HYA (96%) were also successfully removed. Our study generates a single-step purification method for melittin with a high removal rate of PLA2 and HYA, enabling melittin to be fully utilized for its therapeutic purposes. PMID- 27666984 TI - Production of Methanol from Methane by Encapsulated Methylosinus sporium. AB - Massive reserves of methane (CH4) remain unexplored as a feedstock for the production of liquid fuels and chemicals, mainly because of the lack of economically suitable and sustainable strategies for selective oxidation of CH4 to methanol. The present study demonstrates the bioconversion of CH4 to methanol mediated by Type I methanotrophs, such as Methylomicrobium album and Methylomicrobium alcaliphilum. Furthermore, immobilization of a Type II methanotroph, Methylosinus sporium, was carried out using different encapsulation methods, employing sodium-alginate (Na-alginate) and silica gel. The encapsulated cells demonstrated higher stability for methanol production. The optimal pH, temperature, and agitation rate were determined to be pH 7.0, 30 degrees C, and 175 rpm, respectively, using inoculum (1.5 mg of dry cell mass/ml) and 20% of CH4 as a feed. Under these conditions, maximum methanol production (3.43 and 3.73 mM) by the encapsulated cells was recorded. Even after six cycles of reuse, the Na alginate and silica gel encapsulated cells retained 61.8% and 51.6% of their initial efficiency for methanol production, respectively, in comparison with the efficiency of 11.5% observed in the case of free cells. These results suggest that encapsulation of methanotrophs is a promising approach to improve the stability of methanol production. PMID- 27666986 TI - Type 2 pyoverdine from Pseudomonas aeruginosa strain BUP2 as turn-off biosensor for the rapid detection of iron and copper ions in contaminated water. AB - Employing fluorescent quenching mechanism, type 2 pyoverdine (PVD) purified from Pseudomonas aeruginosa strain BUP2 (new strain isolated from the rumen of Malabari goat) was used as a simple, convenient and inexpensive tool for the rapid detection of Fe and Cu ions in contaminated drinking water samples. The fluorescence emitted at lambda460 by PVD (in sterile water), mounted on a glass slide was efficiently quenched by the ions of heavy metals like Fe and Cu. The fluorescence quenching effect of PVD was monitored using UV trans-illuminator, and subsequently quantified and confirmed by spectrofluorimetry. Upon exposure for about 50 sec at 25 degrees C, this quenching efficiency could directly be assessed by naked eye with the aid of a UV trans-illuminator. The linear range of detection for Fe was 1 to 60 uM, while that of Cu was 1 to 20 uM. The limits of detection at uM concentration for Fe3+, Fe2+ and Cu2+ were 0.23, 0.24 and 0.38, respectively. The quenching of fluorescence was more pronounced in Fe-PVD system than Cu-PVD, and this observation was in corroboration with the Pearson acid base concept; being a hard acid, Fe3+ effectively bound with the O-ligands and this ability was less in Cu2+, a border line acid. Briefly, this study proposed the use of type 2 PVD as a turn-off biosensor for the rapid screening of heavy metals like Fe and Cu in drinking water, at ppm levels only with the aid of UV trans illuminator at 25 degrees C in 50 sec. PMID- 27666987 TI - Production of D-Xylonic Acid from Hemicellulose Using Artificial Enzyme Complexes. AB - Lignocellulosic biomass represents a potentially large resource to supply the world's fuel and chemical feedstocks. Enzymatic bioconversion of this substrate offers a reliable strategy for accessing this material under mild reaction conditions. Owing to the complex nature of lignocellulose, many different enzymatic activities are required to function in concert to perform efficient transformation. In nature, large multienzyme complexes are known to effectively hydrolyze lignocellulose into constituent monomeric sugars. We created artificial complexes of enzymes, called rosettazymes, in order to hydrolyze glucuronoxylan, a common lignocellulose component, into its cognate sugar D-xylose and then further convert the D-xylose into D-xylonic acid, a Department of Energy top-30 platform chemical. Four different types of enzymes (endoxylanase, alpha glucuronidase, beta-xylosidase, and xylose dehydrogenase) were incorporated into the artificial complexes. We demonstrated that tethering our enzymes in a complex resulted in significantly more activity (up to 71%) than the same amount of enzymes free in solution. We also determined that varying the enzyme composition affected the level of complex-related activity enhancement as well as overall yield. PMID- 27666988 TI - Fungal Fermentation of Lignocellulosic Biomass for Itaconic and Fumaric Acid Production. AB - The production of high-value chemicals from natural resources as an alternative for petroleum-based products is currently expanding in parallel with biorefinery. The use of lignocellulosic biomass as raw material is promising to achieve economic and environmental sustainability. Filamentous fungi, particularly Aspergillus species, are already used industrially to produce organic acid as well as many enzymes. The production of lignocellulose-degrading enzymes opens the possibility for direct fungal fermentation towards organic acids such as itaconic acid (IA) and fumaric acid (FA). These acids have wide-range applications and potentially addressable markets as platform chemicals. However, current technologies for the production of these compounds are mostly based on submerged fermentation. This work showed the capacity of two Aspergillus species (A. terreus and A. oryzae) to yield both acids by solid-state fermentation and simultaneous saccharification and fermentation. FA was optimally produced at by A. oryzae in simultaneous saccharification and fermentation (0.54 mg/g wheat bran). The yield of 0.11 mg IA/g biomass by A. oryzae is the highest reported in the literature for simultaneous solid-state fermentation without sugar supplements. PMID- 27666989 TI - Improved Electricity Generation by a Microbial Fuel Cell after Pretreatment of Ammonium and Nitrate in Livestock Wastewater with Microbubbles and a Catalyst. AB - Livestock wastewater containing high concentrations of ammonium and nitrate ions was pretreated with microbubbles and an Fe/MgO catalyst prior to its application in microbial fuel cells because high ion concentrations can interfere with current generation. Therefore, tests were designed to ascertain the effect of pretreatment on current generation. In initial tests, the optimal amount of catalyst was found to be 300 g/l. When 1,000 ml/min O2 was used as the oxidant, the removal of ammonium- and nitrate-nitrogen was highest. After the operating parameters were optimized, the removal of ammonium and nitrate ions was quantified. The maximum ammonium removal was 32.8%, and nitrate was removed by up to 75.8% at a 500 g/l catalyst concentration over the course of the 2 h reaction time. The current was about 0.5 mA when livestock wastewater was used without pretreatment, whereas the current increased to 2.14 +/- 0.08 mA when livestock wastewater was pretreated with the method described above. This finding demonstrates that a 4-fold increase in the current can be achieved when using pretreated livestock wastewater. The maximum power density and current density performance were 10.3 W/m3 and 67.5 A/m3, respectively, during the evaluation of the microbial fuel cells driven by pretreated livestock wastewater. PMID- 27666990 TI - Characterization of Polyester Cloth as an Alternative Separator to Nafion Membrane in Microbial Fuel Cells for Bioelectricity Generation Using Swine Wastewater. AB - Polyester cloth (PC) was selected as a prospective inexpensive substitute separator material for microbial fuel cells (MFCs). PC was compared with a traditional Nafion proton exchange membrane (PEM) as an MFC separator by analyzing its physical and electrochemical properties. A single layer of PC showed higher mass transfer (e.g., for O2/H+/ions) than the Nafion PEM; in the case of oxygen mass transfer coefficient (ko), a rate of 50.0 * 10-5 cm.s-1 was observed compared with a rate of 20.8 * 10-5 cm/s in the Nafion PEM. Increased numbers of PC layers were found to reduce the oxygen mass transfer coefficient. In addition, the diffusion coefficient of oxygen (DO) for PC (2.0-3.3 * 10-6 cm2/s) was lower than that of the Nafion PEM (3.8 * 10-6 cm2/s). The PC was found to have a low ohmic resistance (0.29-0.38 Omega) in the MFC, which was similar to that of Nafion PEM (0.31 Omega); this resulted in comparable maximum power density and maximum current density in MFCs with PC and those with Nafion PEMs. Moreover, a higher average current generation was observed in MFCs with PC (104.3 +/- 15.3 A/m3) compared with MFCs with Nafion PEM (100.4 +/- 17.7 A/m3), as well as showing insignificant degradation of the PC surface, during 177 days of use in swine wastewater. These results suggest that PC separators could serve as a low cost alternative to Nafion PEMs for construction of cost-effective MFCs. PMID- 27666991 TI - Selection of Stable Reference Genes for Real-Time Quantitative PCR Analysis in Edwardsiella tarda. AB - Edwardsiella tarda is a gram-negative pathogenic bacterium in aquaculture that can cause hemorrhagic septicemia in fish. Many secreted proteins have already been identified as virulent factors of E. tarda. Moreover, since virulent phenotypes are based on the expression regulation of virulent genes, understanding the expression profile of virulent genes is important. A quantitative RT-PCR is one of the preferred methods for determining different gene expressions. However, this requires the selection of a stable reference gene in E. tarda, which has not yet been systematically studied. Accordingly, this study evaluated nine candidate reference genes (recA, uup, rpoB, rho, topA, gyrA, groEL, rpoD, and 16S rRNA) using the Excel-based programs BestKeeper, GeNorm, and NormFinder under different culture conditions. The results showed that 16S rRNA was more stable than the other genes at different culture growth phases. However, at the same culture time, topA was identified as the reference gene under the conditions of different strains, different culture media, and infection, whereas gyrA was identified under the condition of different temperatures. Thus, in experiments, the expression of gapA and fbaA in E. tarda was analyzed by RT-qPCR using 16S rRNA, recA, and uup as the reference genes. The results showed that 16S rRNA was the most suitable reference gene in this analysis, and that using unsuitable reference genes resulted in inaccurate results. PMID- 27666992 TI - Interaction of Pseudostellaria heterophylla with Quorum Sensing and Quorum Quenching Bacteria Mediated by Root Exudates in a Consecutive Monoculture System. AB - Many plant-pathogenic bacteria are dependent on quorum sensing (QS) to evoke disease. In this study, the population of QS and quorum quenching (QQ) bacteria was analyzed in a consecutive monoculture system of Pseudostellaria heterophylla. The isolated QS strains were identified as Serratia marcescens with SwrIR-type QS system and exhibited a significant increase over the years of monoculture. Only one QQ strain was isolated from newly planted soil sample and was identified as Bacillus thuringiensis, which secreted lactonase to degrade QS signal molecules. Inoculation of S. marcescens to P. heterophylla root could rapidly cause wilt disease, which was alleviated by B. thuringiensis. Furthermore, the expression of lactonase encoded by the aiiA gene in S. marcescens resulted in reduction of its pathogenicity, implying that the toxic effect of S. marcescens on the seedlings was QS-regulated. Meanwhile, excess lactonase in S. marcescens led to reduction in antibacterial substances, exoenzymes, and swarming motility, which might contribute to pathogensis on the seedlings. Root exudates and root tuber extracts of P. heterophylla significantly promoted the growth of S. marcescens, whereas a slight increase of B. thuringiensis was observed in both samples. These results demonstrated that QS-regulated behaviors in S. marcescens mediated by root exudates played an important role in replanting diseases of P. heterophylla. PMID- 27666993 TI - Cloning, Expression, and Characterization of a Cold-Adapted Shikimate Kinase from the Psychrophilic Bacterium Colwellia psychrerythraea 34H. AB - Most cold-adapted enzymes possess higher Km and kcat values than those of their mesophilic counterparts to maximize the reaction rate. This characteristic is often ascribed to a high structural flexibility and improved dynamics in the active site. However, this may be less convincing to cold-adapted metabolic enzymes, which work at substrate concentrations near Km. In this respect, cold adaptation of a shikimate kinase (SK) in the shikimate pathway from psychrophilic Colwellia psychrerythraea (CpSK) was characterized by comparing it with a mesophilic Escherichia coli homolog (EcSK). The optimum temperatures for CpSK and EcSK activity were approximately 30 degrees C and 40 degrees C, respectively. The melting points were 33 degrees C and 45 degrees C for CpSK and EcSK, respectively. The DeltaGH2O (denaturation in the absence of denaturing agent) values were 3.94 and 5.74 kcal/mol for CpSK and EcSK, respectively. These results indicated that CpSK was a cold-adapted enzyme. However, contrary to typical kinetic data, CpSK had a lower Km for its substrate shikimate than most mesophilic SKs, and the kcat was not increased. This observation suggested that CpSK may have evolved to exhibit increased substrate affinity at low intracellular concentrations of shikimate in the cold environment. Sequence analysis and homology modeling also showed that some important salt bridges were lost in CpSK, and higher Arg residues around critical Arg 140 seemed to increase flexibility for catalysis. Taken together, these data demonstrate that CpSK exhibits characteristics of cold adaptation with unusual kinetic parameters, which may provide important insights into the cold adaptation of metabolic enzymes. PMID- 27666994 TI - Improved NADPH Regeneration for Fungal Cytochrome P450 Monooxygenase by Co Expressing Bacterial Glucose Dehydrogenase in Resting-Cell Biotransformation of Recombinant Yeast. AB - Fungal cytochrome P450 (CYP) enzymes catalyze versatile monooxygenase reactions and play a major role in fungal adaptations owing to their essential roles in the production avoid metabolites critical for pathogenesis, detoxification of xenobiotics, and exploitation avoid substrates. Although fungal CYP-dependent biotransformation for the selective oxidation avoid organic compounds in yeast system is advantageous, it often suffers from a shortage avoid intracellular NADPH. In this study, we aimed to investigate the use of bacterial glucose dehydrogenase (GDH) for the intracellular electron regeneration of fungal CYP monooxygenase in a yeast reconstituted system. The benzoate hydroxylase FoCYP53A19 and its homologous redox partner FoCPR from Fusarium oxysporum were co expressed with the BsGDH from Bacillus subtilis in Saccharomyces cerevisiae for heterologous expression and biotransformations. We attempted to optimize several bottlenecks concerning the efficiency of fungal CYP-mediated whole-cell biotransformation to enhance the conversion. The catalytic performance of the intracellular NADPH regeneration system facilitated the hydroxylation of benzoic acid to 4-hydroxybenzoic acid with high conversion in the resting-cell reaction. The FoCYP53A19+FoCPR+BsGDH reconstituted system produced 0.47 mM 4-hydroxybenzoic acid (94% conversion) in the resting-cell biotransformations performed in 50 mM phosphate buffer (pH 6.0) containing 0.5 mM benzoic acid and 0.25% glucose for 24 h at 30 degrees C. The "coupled-enzyme" system can certainly improve the overall performance of NADPH-dependent whole-cell biotransformations in a yeast system. PMID- 27666995 TI - Effects of Lactobacillus curvatus and Leuconostoc mesenteroides on Suan Cai Fermentation in Northeast China. AB - To investigate the effects of Lactobacillus curvatus and Leuconostoc mesenteroides on suan cai (pickled Chinese cabbage) fermentation, L. curvatus and/or Ln. mesenteroides were inoculated into suan cai. Physicochemical indexes were measured, and the microbial dynamics during the fermentation were analyzed by Illumina MiSeq sequencing and quantitative polymerase chain reaction (qPCR). The results showed that inoculation with lactic acid bacteria (LAB) lowered the pH of the fermentation system more rapidly. The decrease in water-soluble carbohydrates in the inoculated treatments occurred more rapidly than in the control. The LAB counts in the control were lower than in other inoculated treatments during the first 12 days of fermentation. According to the Illumina MiSeq sequencing analyses, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Cyanobacteria, Fusobacteria, and Verrucomicrobia were present in the fermentations, along with other unclassified bacteria. Generally, Firmicutes was predominant during the fermentation in all treatments. At the genus level, 16 genera were detected. The relative abundance of Lactobacillus in all inoculated treatments was higher than in the control. The relative abundance of Lactobacillus in the treatments containing L. curvatus was higher than in the Ln. mesenteroides-only treatment. The relative abundance of Leuconostoc in the Ln. mesenteroides-containing treatments increased continuously throughout the fermentation. Leuconostoc was highest in the Ln. mesenteroides-only treatment. According to the qPCR results, L. curvatus and/or Ln. mesenteroides inoculations could effectively inhabit the fermentation system. L. curvatus dominated the fermentation in the inoculated treatments. PMID- 27666996 TI - Supragingival Plaque Microbial Community Analysis of Children with Halitosis. AB - As one of the most complex human-associated microbial habitats, the oral cavity harbors hundreds of bacteria. Halitosis is a prevalent oral condition that is typically caused by bacteria. The aim of this study was to analyze the microbial communities and predict functional profiles in supragingival plaque from healthy individuals and those with halitosis. Ten preschool children were enrolled in this study; five with halitosis and five without. Supragingival plaque was isolated from each participant and 16S rRNA gene pyrosequencing was used to identify the microbes present. Samples were primarily composed of Actinobacteria, Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, and Candidate phylum TM7. The alpha and beta diversity indices did not differ between healthy and halitosis subjects. Fifteen operational taxonomic units (OTUs) were identified with significantly different relative abundances between healthy and halitosis plaques, and included the phylotypes of Prevotella sp., Leptotrichia sp., Actinomyces sp., Porphyromonas sp., Selenomonas sp., Selenomonas noxia, and Capnocytophaga ochracea. We suggest that these OTUs are candidate halitosis associated pathogens. Functional profiles were predicted using PICRUSt, and nine level-3 KEGG Orthology groups were significantly different. Hub modules of co occurrence networks implied that microbes in halitosis dental plaque were more highly conserved than microbes of healthy individuals' plaque. Collectively, our data provide a background for the oral microbiota associated with halitosis from supragingival plaque, and help explain the etiology of halitosis. PMID- 27666997 TI - Reply to Hao Lun Luo, Yen Ta Chen, Yuan Tso Cheng, and Po Hui Chiang's Letter to the Editor re: Re: Thomas Seisen, Benoit Peyronnet, Jose Luis Dominguez-Escrig, et al. Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel. Eur Urol 2016;70:1052-68: The Key Role of Flexible Ureterorenoscopy in Kidney-sparing Surgery for Upper Tract Urothelial Carcinoma. PMID- 27666998 TI - Reply from Authors re: Jens Uwe Stolzenburg, Iason Kyriazis, Evangelos Liatsikos. Postoperative Lymphocele Formation after Pelvic Lymph Node Dissection at the Time of Radical Prostatectomy Should Not Be Considered an Inevitable Consequence of the Approach. Eur Urol 2017;71:159-60: Which Lymphatic Vessels Have To Be Secured During Pelvic Lymph Node Dissection for Prostate Cancer? PMID- 27667000 TI - Pancreatic accessory spleen and false positive. PMID- 27666999 TI - A potential pitfall in the use of 68Ga-PSMA PET/CT: Anthracosis. PMID- 27667001 TI - 18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging. AB - OBJECTIVE: Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. MATERIAL AND METHODS: A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. RESULTS: In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. CONCLUSIONS: PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes. PMID- 27667002 TI - Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway. AB - Accumulating evidence suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. In order to test the hypothesis that LPS-induced inflammatory response might damage mitochondrial structure and function leading to nigral dopaminergic neuron loss, we injected LPS or saline into the striatum of rats. Here, we found that intrastriatal LPS induced deficit in mitochondrial respiration, damage to mitochondrial cristae, mitochondrial oxidation and nitration. Finally, we found significant loss of dopaminergic neurons in the substantia nigra one week after LPS injection. This study indicates that LPS-induced dopaminergic neurodegeneration might be exerted by mitochondrial injury. PMID- 27667003 TI - Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information. AB - An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. PMID- 27667004 TI - Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum. AB - Addiction is a disorder of behavioral symptoms including enhanced incentive salience of drug-associated cues, but also a negative affective state. Cocaine evoked synaptic plasticity in the reward system, particularly the nucleus accumbens (NAc), drives drug-adaptive behavior. However, how information is integrated downstream of the NAc remains unclear. Here, we identify the ventral pallidum (VP) as a site of convergence of medium spiny neurons expressing dopamine (DA) receptor type 1 (D1-MSNs) and type 2 (D2-MSNs) of the NAc. Repeated in vivo cocaine exposure potentiated output of D1-MSNs, but weakened output of D2 MSNs, occluding LTP and LTD at these synapses, respectively. Selectively restoring basal transmission at D1-MSN-to-VP synapses abolished locomotor sensitization, whereas restoring transmission at D2-MSN-to-VP synapses normalized motivational deficits. Our results support a model by which drug-evoked synaptic plasticity in the VP mediates opposing behavioral symptoms; targeting the VP may provide novel therapeutic strategies for addictive disorders. PMID- 27667005 TI - Balancing the Robustness and Efficiency of Odor Representations during Learning. AB - For reliable stimulus identification, sensory codes have to be robust by including redundancy to combat noise, but redundancy sacrifices coding efficiency. To address how experience affects the balance between the robustness and efficiency of sensory codes, we probed odor representations in the mouse olfactory bulb during learning over a week, using longitudinal two-photon calcium imaging. When mice learned to discriminate between two dissimilar odorants, responses of mitral cell ensembles to the two odorants gradually became less discrete, increasing the efficiency. In contrast, when mice learned to discriminate between two very similar odorants, the initially overlapping representations of the two odorants became progressively decorrelated, enhancing the robustness. Qualitatively similar changes were observed when the same odorants were experienced passively, a condition that would induce implicit perceptual learning. These results suggest that experience adjusts odor representations to balance the robustness and efficiency depending on the similarity of the experienced odorants. PMID- 27667006 TI - How Azobenzene Photoswitches Restore Visual Responses to the Blind Retina. AB - Azobenzene photoswitches confer light sensitivity onto retinal ganglion cells (RGCs) in blind mice, making these compounds promising candidates as vision restoring drugs in humans with degenerative blindness. Remarkably, photosensitization manifests only in animals with photoreceptor degeneration and is absent from those with intact rods and cones. Here we show that P2X receptors mediate the entry of photoswitches into RGCs, where they associate with voltage gated ion channels, enabling light to control action-potential firing. All charged photoswitch compounds require permeation through P2X receptors, whose gene expression is upregulated in the blind retina. Photoswitches and membrane impermeant fluorescent dyes likewise penetrate through P2X receptors to label a subset of RGCs in the degenerated retina. Electrophysiological recordings and mapping of fluorescently labeled RGC dendritic projections together indicate that photosensitization is highly selective for OFF-RGCs. Hence, P2X receptors are a natural conduit allowing cell-type-selective and degeneration-specific delivery of photoswitches to restore visual function in blinding disease. PMID- 27667009 TI - Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. AB - OBJECTIVE: To determine whether an up-to-date systematic review and meta-analysis of observational studies would support the previously suggested associations regarding prenatal selective serotonin reuptake inhibitor (SSRI) use and the risk for autism spectrum disorders (ASD) in children. METHODS: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox databases were searched; observational studies with an exposed and unexposed group were included. RESULTS: The meta-analysis of case-control studies demonstrated a significantly increased risk of ASD in the children whose mothers were prenatally exposed to SSRIs during different exposure time windows (except third trimester). The qualitative review of the cohort studies suggested inconsistent findings. CONCLUSIONS: The significant association between preconception-only SSRI exposure and ASD in the children and negative/inconsistent findings among cohort studies weaken the significant associations detected in this meta-analysis. We suggest that confounding by indication still cannot be ruled out regarding prenatal SSRI exposure and ASD in children. PMID- 27667007 TI - CaMKII Phosphorylation of TARPgamma-8 Is a Mediator of LTP and Learning and Memory. AB - Protein phosphorylation is an essential step for the expression of long-term potentiation (LTP), a long-lasting, activity-dependent strengthening of synaptic transmission widely regarded as a cellular mechanism underlying learning and memory. At the core of LTP is the synaptic insertion of AMPA receptors (AMPARs) triggered by the NMDA receptor-dependent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). However, the CaMKII substrate that increases AMPAR mediated transmission during LTP remains elusive. Here, we identify the hippocampus-enriched TARPgamma-8, but not TARPgamma-2/3/4, as a critical CaMKII substrate for LTP. We found that LTP induction increases TARPgamma-8 phosphorylation, and that CaMKII-dependent enhancement of AMPAR-mediated transmission requires CaMKII phosphorylation sites of TARPgamma-8. Moreover, LTP and memory formation, but not basal transmission, are significantly impaired in mice lacking CaMKII phosphorylation sites of TARPgamma-8. Together, these findings demonstrate that TARPgamma-8 is a crucial mediator of CaMKII-dependent LTP and therefore a molecular target that controls synaptic plasticity and associated cognitive functions. PMID- 27667010 TI - Allogeneic Hematopoietic Cell Transplantation for Leukemic Transformation Preceded by Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Nationwide Survey by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. AB - To clarify the outcome of allogeneic hematopoietic cell transplantation (HCT) for leukemic transformation (LT) preceded by Philadelphia chromosome-negative (Ph neg) myeloproliferative neoplasms (MPNs), we conducted a retrospective study using the national registry database of the Japan Society for Hematopoietic Cell Transplantation. From 2000 to 2013, 39 patients underwent their first allogeneic HCT with related bone marrow or peripheral blood stem cells (n = 8), unrelated bone marrow (n = 15), and unrelated umbilical cord blood (n = 16). The median patient age was 57 years. The underlying Ph-neg MPNs included 21 cases of essential thrombocythemia, 11 cases of primary myelofibrosis, and 7 cases of polycythemia vera. The median interval between the diagnosis of LT and transplantation was 134 days. Thirty-two cases (82%) were not in remission at the time of transplantation. The 2-year overall survival rate was 29.2% (95% confidence interval [CI], 15.5% to 44.3%). The median follow-up of the surviving patients was 1989.5 days (range, 285 to 3270). The cumulative incidences of relapse and nonrelapse mortality at 2 years were 34.4% (95% CI, 19.6% to 49.8%) and 34.2% (95% CI, 19.6% to 49.4%), respectively. The study results suggested that allogeneic HCT provides long-term survival in approximately one-third of patients with LT preceded by Ph-neg MPNs. PMID- 27667008 TI - Gamma-Rhythmic Gain Modulation. AB - Cognition requires the dynamic modulation of effective connectivity, i.e., the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backward to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation. PMID- 27667011 TI - Comparison of Donor Sources in Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Nationwide Retrospective Study. AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best therapeutic option for childhood high-risk acute leukemia. However, which donor source is optimal for children lacking an identical sibling remains unclear. To evaluate the clinical impact of donor source on allo-HSCT in childhood acute leukemia, we analyzed data from 577 children who underwent allo-HSCT after a myeloablative regimen during first or second complete remission from 2005 to 2012, using registry data of the Japan Society for Hematopoietic Cell Transplantation, and we compared outcomes of 7/8 to 8/8 HLA allelic-matched unrelated bone marrow transplantation (UR-BMT, n = 218) and 4/6 to 6/6 HLA allelic-matched unrelated cord blood transplantation (UR-CBT, n = 200) to those of HLA-identical related bone marrow transplantation (ID-BMT, n = 159). The median follow-up of survivors was 40.0 months. Three-year overall survival (OS) and leukemia-free survival (LFS) rates for ID-BMT, UR-BMT, and UR-CBT were 74.8% and 69.0%, 75.0% and 69.6%, and 71.8% and 63.8%, respectively. The multivariate analysis demonstrated that OS and LFS for the 3 groups are comparable, although UR-CBT carries a greater risk of nonrelapse mortality (hazard ratio, 2.20; P = .03, compared to ID-BMT) in the myeloablative setting for childhood high-risk acute leukemia. PMID- 27667012 TI - Long-Lasting Protective Effect of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Stem Cell Transplantation. AB - Patients with acute myeloid leukemia (AML) during induction chemotherapy and those who receive allogeneic hematopoietic stem cell transplantation (HSCT) are at higher risk of invasive fungal infections (IFI). In the present study, we investigated whether the risk of IFI in AML patients receiving HSCT might be affected by the antifungal prophylaxis with posaconazole administered during the induction/salvage chemotherapy treatment. Between August 2001 and April 2015, 130 patients with AML received itraconazole/fluconazole (group A) and 99 received posaconazole (group B) as antifungal prophylaxis after induction/salvage chemotherapy at 7 Italian centers and all patients received fluconazole as antifungal prophylaxis after HSCT. The median duration of antifungal prophylaxis after induction/salvage chemotherapy was significantly longer for patients in group A than for those in group B (24 days versus 20 days, P = .019). The 1-year cumulative incidence of proven/probable IFI after HSCT was 14% and 4% in group A and group B, respectively (P = .012). Fungal-free survival and overall survival at 1 year after HSCT were 66% and 70% in group A, and 75% and 77% in group B (P = .139 and P = .302), respectively. Multivariate logistic analysis identified the use of alternative donors (matched unrelated donor: odds ratio [OR], 3.25; haploidentical/partially matched related donor: OR, 3.19), antifungal prophylaxis with itraconazole/fluconazole (OR, 3.82), and reduced-intensity conditioning (OR, 4.92) as independent risk factors for the development of IFI after HSCT. In summary, the present study suggests that the protective effects of posaconazole during induction/salvage chemotherapy for AML patients may have long-lasting benefits and eventually contribute to reduce the risk of IFI when patients undergo allogeneic HSCT. PMID- 27667013 TI - Acidity-Controlled Conducting Polymer Films for Organic Thermoelectric Devices with Horizontal and Vertical Architectures. AB - Organic thermoelectric devices (OTEDs) are recognized one of the next generation energy conversion platforms because of their huge potentials for securing electricity continuously from even tiny heat sources in our daily life. The advantage of OTEDs can be attributable to the design freedom in device shapes and the low-cost fabrication by employing solution coating processes at low temperatures. As one of the major OTE materials to date, poly(3,4 ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has been used, but no study has been yet carried out on its acidity control even though the acidic components in OTEDs can seriously affect the device performance upon operation. Here we demonstrate that the addition of aniline (a weak base) can control the acidity of PEDOT:PSS and enhance the performance of OTEDs. In particular, the vertical OTEDs with aniline-doped PEDOT:PSS films (active area = 1.0 cm2) could continuously generate electricity (0.06 nW) even at low temperatures (<38 degrees C) when they were mounted on a desk lamp (power = 24 W). PMID- 27667014 TI - Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells? AB - : Recently accumulating evidence has put into question the role of large multinucleated giant cells (MNGCs) around bone biomaterials. While cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials, it was originally thought that specifically in bone tissues, all giant cells were bone-resorbing osteoclasts whereas foreign body giant cells (FBGCs) were found associated with a connective tissue foreign body reaction resulting in fibrous encapsulation and/or material rejection. Despite the great majority of bone grafting materials routinely found with large osteoclasts, a special subclass of bone biomaterials has more recently been found surrounded by large giant cells virtually incapable of resorbing bone grafts even years after their implantation. While original hypotheses believed that a 'foreign body reaction' may be taking place, histological data retrieved from human samples years after their implantation have put these original hypotheses into question by demonstrating better and more stable long-term bone volume around certain bone grafts. Exactly how or why this 'special' subclass of giant cells is capable of maintaining long-term bone volume, or methods to scientifically distinguish them from osteoclasts remains extremely poorly studied. The aim of this review article was to gather the current available literature on giant cell markers and differences in expression patterns between osteoclasts and MNGCs utilizing 19 specific markers including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro inflammatory M1-MNGCs (previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. STATEMENT OF SIGNIFICANCE: This review article presents 19 specific cell-surface markers to distinguish between osteoclasts and MNGCs including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (often previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. The proposed concepts and guidelines aims to guide the next wave of research facilitating the differentiation between osteoclast/MNGCs formation, as well as provides the basis for increasing our understanding of the exact function of MNGCs in bone tissue/biomaterial homeostasis. PMID- 27667015 TI - Electrospun polystyrene scaffolds as a synthetic substrate for xeno-free expansion and differentiation of human induced pluripotent stem cells. AB - : The use of human induced pluripotent stem cells (hiPSCs) for clinical tissue engineering applications requires expansion and differentiation of the cells using defined, xeno-free substrates. The screening and selection of suitable synthetic substrates however, is tedious, as their performance relies on the inherent material properties. In the present work, we demonstrate an alternative concept for xeno-free expansion and differentiation of hiPSCs using synthetic substrates, which hinges on the structure-function relationship between electrospun polystyrene scaffolds (ESPS) and pluripotent stem cell growth. ESPS of differential porosity was obtained by fusing the fibers at different temperatures. The more porous, loosely fused scaffolds were found to efficiently trap the cells, leading to a large number of three-dimensional (3D) aggregates which were shown to be pluripotent colonies. Immunostaining, PCR analyses, in vitro differentiation and in vivo teratoma formation studies demonstrated that these hiPSC aggregates could be cultured for up to 10 consecutive passages (P10) with maintenance of pluripotency. Flow cytometry showed that more than 80% of the cell population stained positive for the pluripotent marker OCT4 at P1, P5 and P10. P10 cells could be differentiated to neuronal-like cells and cultured within the ESPS for up to 18months. Our results suggest the usefulness of a generic class of synthetic substrates, exemplified by ESPS, for 'trapped aggregate culture' of hiPSCs. STATEMENT OF SIGNIFICANCE: To realize the potential of human induced pluripotent stem cells (hiPSCs) in clinical medicine, robust, xeno-free substrates for expansion and differentiation of iPSCs are required. In the existing literature, synthetic materials have been reported that meet the requirement for non-xenogeneic substrates. However, the self-renewal and differentiation characteristics of hiPSCs are affected differently by the biocompatibility and physico-chemical properties of individual substrates. Although some rules based on chemical structure and substrate rigidity have been developed, most of these efforts are still empirical, and most synthetic substrates must still be rigorously screened for suitability. In this paper, we demonstrate an alternative concept for xeno-free expansion and differentiation of hiPSCs using synthetic substrates, which hinges on the structure-function relationship between electrospun polystyrene scaffolds (ESPS) and pluripotent stem cell growth. ESPS of differential porosity was obtained by fusing the fibers at different temperatures. The more porous, loosely fused scaffold was found to efficiently trap the cells, leading to a large number of three-dimensional (3D) aggregates. In the form of these trapped aggregates, we showed that hiPSCs could be cultured for up to 10 consecutive passages (P10) with maintenance of pluripotency, following which they could be differentiated to a chosen lineage. We believe that this novel, generic class of synthetic substrates that employs 'trapped aggregate culture' for expansion and differentiation of hiPSCs is an important conceptual advance, and would be of high interest to the readership of Acta Biomaterialia. PMID- 27667016 TI - A fiber-progressive-engagement model to evaluate the composition, microstructure, and nonlinear pseudoelastic behavior of porcine arteries and decellularized derivatives. AB - : The theoretical fiber-progressive-engagement model was proposed to describe the pseudoelastic behavior of an artery pre- and post-decellularization treatments. Native porcine arteries were harvested and decellularized with 0.05% trypsin for 12 h. The uniaxial tensile test data were fitted to the fiber-progressive engagement model proposed herein. The effects of decellularization on the morphology, structural characteristics, and composition of vessel walls were studied. The experimental stress-strain curve was fitted to the model in the longitudinal and circumferential direction, which demonstrated the adequacy of the proposed model (R2>0.99). The initial and turning strains were similar in the longitudinal and circumferential directions in the aorta, suggesting the occurrence of collagen conjugation in both directions. Discrepancies in the initial and turning strain and initial and stiff modulus in both directions in the coronary artery revealed the anisotropic features of this vessel. Decellularization induced a decrease in the initial and turning strains, a slight change in the initial modulus, and a substantial decrease in the stiffness modulus. The decrease in the initial and turning strain can be attributed to the loss of waviness of collagen bundles because of the considerable decrease in elastin and glycosaminoglycan contents. This simple non-linear model can be used to determine the fiber modulus and waviness degree of vascular tissue. Based on these results, this mechanical test can be used as a screening tool for the selection of an optimized decellularization protocol for arterial tissues. STATEMENT OF SIGNIFICANCE: Decellularized vascular graft has potential in clinical application, such as coronary artery bypass surgery, peripheral artery bypass surgery or microsurgery. An ideal decellularization protocol requires balance in cell removal efficiency and extracellular matrix preserving. Both biochemical and biomechanical properties are crucial to the success of scaffold in cell seeding and animal study. A comprehensive understanding of the composition, microstructure, and mechanical behavior of the arterial wall is the key to the development of decellularized vascular grafts. For this purpose, we proposed this "Fiber-Progressive-Engagement" model to evaluate the microstructure, composition and mechanical properties of porcine coronary artery. The model provides a new perspective regarding the non-linear behavior of arterial tissue and its decellularized derivatives. It can be widely applied to different types of tissues, as demonstrated in the aorta and coronary artery. This model has several advantages; it provides an improved fit of non-linear curves (R2>0.99), can be used to elucidate the pseudoelastic properties of porcine vascular tissues using the concept of fiber engagement, and can estimate an elastic modulus with greater accuracy (compared to the graphical estimation or calculation by simple linear fittings), as well as to plot typical stress-strain curves. PMID- 27667017 TI - Cold atmospheric plasma (CAP) surface nanomodified 3D printed polylactic acid (PLA) scaffolds for bone regeneration. AB - : Three-dimensional (3D) printing is a new fabrication method for tissue engineering which can precisely control scaffold architecture at the micron scale. However, scaffolds not only need 3D biocompatible structures that mimic the micron structure of natural tissues, they also require mimicking of the nano scale extracellular matrix properties of the tissue they intend to replace. In order to achieve this, the objective of the present in vitro study was to use cold atmospheric plasma (CAP) as a quick and inexpensive way to modify the nano scale roughness and chemical composition of a 3D printed scaffold surface. Water contact angles of a normal 3D printed poly-lactic-acid (PLA) scaffold dramatically dropped after CAP treatment from 70+/-2 degrees to 24+/-2 degrees . In addition, the nano-scale surface roughness (Rq) of the untreated 3D PLA scaffolds drastically increased (up to 250%) after 1, 3, and 5min of CAP treatment from 1.20nm to 10.50nm, 22.90nm, and 27.60nm, respectively. X-ray photoelectron spectroscopy (XPS) analysis showed that the ratio of oxygen to carbon significantly increased after CAP treatment, which indicated that the CAP treatment of PLA not only changed nano-scale roughness but also chemistry. Both changes in hydrophilicity and nano-scale roughness demonstrated a very efficient plasma treatment, which in turn significantly promoted both osteoblast (bone forming cells) and mesenchymal stem cell attachment and proliferation. These promising results suggest that CAP surface modification may have potential applications for enhancing 3D printed PLA bone tissue engineering materials (and all 3D printed materials) in a quick and an inexpensive manner and, thus, should be further studied. STATEMENT OF SIGNIFICANCE: Three-dimensional (3D) printing is a new fabrication method for tissue engineering which can precisely control scaffold architecture at the micron-scale. Although their success is related to their ability to exactly mimic the structure of natural tissues and control mechanical properties of scaffolds, 3D printed scaffolds have shortcomings such as limited mimicking of the nanoscale extracellular matrix properties of the tissue they intend to replace. In order to achieve this, the objective of the present in vitro study was to use cold atmospheric plasma (CAP) as a quick and inexpensive way to modify the nanoscale roughness and chemical composition of a 3D printed scaffold surface. The results indicated that using CAP surface modification could achieve a positive change of roughness and surface chemistry. Results showed that both hydrophilicity and nanoscale roughness changes to these scaffolds after CAP treatment played an important role in enhancing bone cell and mesenchymal stem cell attachment and functions. More importantly, this technique could be used for many 3D printed polymer-based biomaterials to improve their properties for numerous applications. PMID- 27667018 TI - Nanopattern-induced osteogenic differentiation of stem cells - A systematic review. AB - : It is well known that biomaterials topography can influence the behavior of stem cells. Nevertheless, the fundamentals and the impact of nanoscale topography are just emerging. The main objective of this review has been to reveal the state of-the-art on the effects of controlled nanoscale topographies (nanopatterns) on in vitro osteogenic differentiation of mesenchymal stem cells (MSCs) in the absence of osteogenic supplements. The findings indicate that nanopatterns with specific feature sizes, spatial arrangements, or shapes may induce osteogenic differentiation of MSCs. Regardless of substrate chemistry, nanopattern-induced osteogenic differentiation is associated with large focal adhesions, enhanced cell areas, and well organized cytoskeleton. These results suggest that earlier interactions between nanopattern features and cell receptors are involved, with effects on the entire cell structure and subsequent differentiation. Such events are possibly mediated by nanotopography-induced mechanotransduction pathways. The findings so far reveal that nanoscale topography has potential for directing differentiation of MSCs towards the osteogenic lineage in non-osteogenic media and should be harnessed for possible synergistic effects in bone regenerative therapies. STATEMENT OF SIGNIFICANCE: The use of nanotopography to induce cellular responses represents a novel and rapidly growing area of research. Nevertheless, the findings and trends so far are difficult to identify and discuss mostly due to a non-systematic research approach. The present manuscript is providing a systematic review focused on nanopattern-induced osteogenic differentiation of mesenchymal stem cells. The coverage of the most relevant aspects including nanopatterns fabrication methods, their effects on osteogenic differentiation of mesenchymal stem cells as well as the related effects on adhesion and cell morphology has enabled an integrated discussion including the potential mechanotransduction mechanisms involved. Furthermore, a clear distinction between the studies that use only surface nanotopographies and the ones that mix nanotopographical features with osteogenic supplements has been made. This delineation is essential for revealing and understanding the role of biomaterial's nanotopography per se on stem cells differentiation based on which novel osteoinductive biomaterials can be developed. PMID- 27667019 TI - In situ mechanical and molecular investigations of collagen/apatite biomimetic composites combining Raman spectroscopy and stress-strain analysis. AB - : We report the design, fabrication and application of a novel micro electromechanical device coupled to a confocal Raman microscope that enables in situ molecular investigations of micro-fibers under uniaxial tensile load. This device allows for the mechanical study of micro-fibers with diameters in the range between 10 and 100MUm and lengths of several hundred micrometers. By exerting forces in the mN range, the device enables an important force range to be accessed between that of atomic force microscopy and macroscopic stress-strain measurement devices. The load is varied using a stiffness-calibrated glass micro needle driven by a piezo-translator during simultaneous Raman microscopy imaging. The method enables experiments probing the molecular response of micro-fibers to external stress. This set-up was applied to biomimetic non-mineralized and mineralized collagen micro-fibers revealing that above 30% mineralization the proline-related Raman band shows a pronounced response to stress, which is not observed in non-mineralized collagen. This molecular response coincides with a strong increase in the Young's modulus from 0.5 to 6GPa for 0% and 70% mineralized collagen, respectively. Our results are consistent with a progressive interlocking of the collagen triple-helices by apatite nanocrystals as the degree of mineralization increases. STATEMENT OF SIGNIFICANCE: Collagen and apatite are the main constituents regulating the mechanical properties of bone. Hence, an improved understanding of the impact of mineralization on these properties is of large interest for the scientific community. This paper presents systematic studies of synthetic collagen microfibers with increasing apatite content and their response to tensile stress by using a novel self-made electromechanical device combined with a Raman spectrometer for molecular level studies. The impact of apatite on the mechanical and molecular response of collagen is evaluated giving important insights into the interaction between the mineral and organic phases. Therefore our findings expand the fundamental understanding of the mechanics of the apatite/collagen system relevant for the design of bio composites with similar bio-mimicking properties for e.g. bone regrowth in medical applications. PMID- 27667020 TI - Extracellular protease derived from lactic acid bacteria stimulates the fermentative lactic acid production from the by-products of rice as a biomass refinery function. AB - A lactic acid producing bacterium, Lactobacillus rhamnosus M-23, newly isolated from a rice washing drainage storage tank was found to produce l-(+)-lactic acid from a non-sterilized mixture of rice washing drainage and rice bran without any additions of nutrients under the simultaneous saccharification and fermentation (SSF) process. This strain has the ability to utilize the non-sterilized rice washing drainage and rice bran as a source of carbohydrate, saccharifying enzymes and nutrients for lactic acid production. Observation of extracellular protease activity in SSF culture broth showed that a higher protease activity was present in strain M-23 than in other isolated lactic acid producing bacteria (LABs). To investigate the structural changes of solid particles of rice washing drainage throughout LAB cultivation, scanning electron microscopic (SEM) observation and Fourier transform infrared-spectroscopy (FT-IR) analysis were performed. The results of the SEM observation showed that the surface material could be removed from solid particles of rice washing drainage treated by culture broth (supernatant) of strain M-23, thus exposing the crystal structure of the starch particle surface. The results of the FT-IR analysis revealed that the specific transmittance decrease of the CC and CO stretching and OH group of the solid particles of the rice washing drainage were highly correlated with the produced lactic acid concentration and extracellular protease activity, respectively. These results demonstrate the high lactic acid producing ability of strain M-23 from a non-sterilized mixture of rice washing drainage and rice bran under the SSF condition due to the removal of proteinaceous material and exposure of the starch particle surface by extracellular protease. PMID- 27667021 TI - Proliferation of metanephric mesenchymal cells is inhibited by miR-743a-mediated WT1 suppression in vitro. AB - To seek out the potential microRNAs (miRNAs) that target Wilms' tumor suppressor 1 (WT1), a transcription factor required for progenitor proliferation as well as normal development of the kidney, and to clarify the effects of the miRNAs on WT1, the 3'-untranslated region (3'-UTR) of WT1 was initially analyzed and miR 743a, a seldom-reported miRNA, was identified. In the present paper, luciferase reporter assays were performed to confirm that miR-743a is able to directly target the 3'-UTR of WT1. Subsequently, reverse transcription-quantitative polymerase chain reaction, combined with western blotting analyses, were performed, and the results revealed a significant inhibition of WT1 at the mRNA and the protein levels. Furthermore, a 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay, coupled with a WT1 rescue strategy, demonstrated that miR 743a inhibited the proliferation of metanephric mesenchymal (MM) cells, in part by targeting WT1. In conclusion, by targeting WT1, miR-743a suppresses the proliferation of MM cells in vitro, and probably possesses vital functions in kidney development and kidney-associated diseases. PMID- 27667022 TI - Atomically thin quantum light-emitting diodes. AB - Transition metal dichalcogenides are optically active, layered materials promising for fast optoelectronics and on-chip photonics. We demonstrate electrically driven single-photon emission from localized sites in tungsten diselenide and tungsten disulphide. To achieve this, we fabricate a light emitting diode structure comprising single-layer graphene, thin hexagonal boron nitride and transition metal dichalcogenide mono- and bi-layers. Photon correlation measurements are used to confirm the single-photon nature of the spectrally sharp emission. These results present the transition metal dichalcogenide family as a platform for hybrid, broadband, atomically precise quantum photonics devices. PMID- 27667023 TI - Coxsackievirus A16 induced neurological disorders in young gerbils which could serve as a new animal model for vaccine evaluation. AB - Coxsackievirus A16 (CA16) is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD) in the Asia-pacific region. Although CA16 infections are generally mild, severe neurological manifestations or even death has been reported. Studies on CA16 pathogenesis and vaccine development are severely hampered because the small animal models that are currently available show major limitations. In this study, gerbils (Meriones unguiculatus) were investigated for their suitability as an animal model to study CA16 pathogenesis and vaccine development. Our results showed that gerbils up to the age of 21 days were fully susceptible to CA16 and all died within five days post-infection. CA16 showed a tropism towards the skeletal muscle, spinal cord and brainstem of gerbils, and severe lesions, including necrosis, were observed. In addition, an inactivated CA16 whole-virus vaccine administrated to gerbils was able to provide full protection to the gerbils against lethal doses of CA16 strains. These results demonstrate that gerbils are a suitable animal model to study CA16 infection and vaccine development. PMID- 27667024 TI - Interferon-gamma alters the microRNA profile of umbilical cord-derived mesenchymal stem cells. AB - Numerous studies have demonstrated that interferon-gamma (IFN-gamma) is an important inflammatory cytokine, which may activate the immunomodulatory abilities of mesenchymal stem cells (MSCs), and may influence certain other functions of these cells. MicroRNAs are small non-coding RNAs that regulate the majority of the biological functions of cells and are important in a variety of biological processes. However, few studies have been performed to investigate whether IFN-gamma affects the microRNA profile of MSCs. The aim of the present study was to analyze the microRNA profile of MSCs derived from the umbilical cord (UC-MSCs) cultured in the presence or absence of IFN-gamma (IFN-UC-MSCs). An array that detects 754 microRNAs was used to determine the expression profiles. Statistical analysis of the array data revealed that 8 microRNAs were significantly differentially expressed in UC-MSCs and IFN-UC-MSCs. Reverse transcription-quantitative polymerase chain reaction validated the differential expression of the 8 identified microRNAs. The target genes of the 8 microRNAs were predicted through two online databases, TargetScan and miRanda, and the predicted results were screened by bioinformatics analysis. The majority of the target genes were involved in the regulation of transcription, signal transduction, proliferation, differentiation and migration. These results may provide insight into the mechanism underlying the regulation of the biological functions of MSCs by IFN-gamma, in particular the immunomodulatory activity. PMID- 27667025 TI - The effects on plasma L-arginine levels of combined oral L-citrulline and L arginine supplementation in healthy males. AB - We investigated the effects of combining 1 g of l-citrulline and 1 g of l arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined. PMID- 27667026 TI - Development and characterisation of highly antibiotic resistant Bartonella bacilliformis mutants. AB - The objective was to develop and characterise in vitro Bartonella bacilliformis antibiotic resistant mutants. Three B. bacilliformis strains were plated 35 or 40 times with azithromycin, chloramphenicol, ciprofloxacin or rifampicin discs. Resistance-stability was assessed performing 5 serial passages without antibiotic pressure. MICs were determined with/without Phe-Arg-beta-Napthylamide and artesunate. Target alterations were screened in the 23S rRNA, rplD, rplV, gyrA, gyrB, parC, parE and rpoB genes. Chloramphenicol and ciprofloxacin resistance were the most difficult and easiest (>37.3 and 10.6 passages) to be selected, respectively. All mutants but one selected with chloramphenicol achieved high resistance levels. All rifampicin, one azithromycin and one ciprofloxacin mutants did not totally revert when cultured without antibiotic pressure. Azithromycin resistance was related to L4 substitutions Gln-66 -> Lys or Gly-70 -> Arg; L4 deletion Delta62-65 (Lys-Met-Tyr-Lys) or L22 insertion 83::Val-Ser-Glu-Ala-His Val-Gly-Lys-Ser; in two chloramphenicol-resistant mutants the 23S rRNA mutation G2372A was detected. GyrA Ala-91 -> Val and Asp-95 -> Gly and GyrB Glu474 -> Lys were detected in ciprofloxacin-resistant mutants. RpoB substitutions Gln-527 -> Arg, His-540 -> Tyr and Ser-545 -> Phe plus Ser-588 -> Tyr were detected in rifampicin-resistant mutants. In 5 mutants the effect of efflux pumps on resistance was observed. Antibiotic resistance was mainly related to target mutations and overexpression of efflux pumps, which might underlie microbiological failures during treatments. PMID- 27667027 TI - Efficacy and safety of TNF-alpha inhibitors for active ankylosing spondylitis patients: Multiple treatment comparisons in a network meta-analysis. AB - Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with impact on axial skeleton, peripheral joints and enthuses, and it may result in severe disabilities of those parts. Tumor necrosis factor-alpha (TNF-alpha) inhibitors are considered as an effective treatment for patients with active AS. In this study, we conducted a network meta-analysis to compare the clinical outcomes of active AS patients treated with TNF-alpha inhibitors. Randomized controlled trials (RCTs) evaluating the efficacy and safety of TNF-alpha inhibitors were retrieved in literature search and selected for meta-analysis. Changes in ASAS20 response, ASAS40 response and BASDAI 50% response were regarded as efficacy outcomes; serious adverse events (SAE) and all cause withdrawals were regarded as safety outcomes. Both traditional pairwise meta-analysis and network meta analysis were performed. The results showed that adalimumab and infliximab had better clinical outcomes. Infliximab consistently appeared to be the most effective TNF-alpha inhibitors with a high risk of adverse events for patients with active AS; meanwhile, adalimumab ranked highest with respect to adverse effects with efficacy secondary to infliximab. As a result, we were unable to conclude the optimal TNF-alpha inhibitor and this issue should be solved by future researchers. PMID- 27667028 TI - Quality of life and exercise performance in unoperated children with anomalous aortic origin of a coronary artery from the opposite sinus of valsalva. AB - BACKGROUND: Anomalous aortic origin of a coronary artery is a congenital cardiac condition that can be associated with increased risk of sudden death. To date, quality of life and exercise performance have not been evaluated in patients with this condition who do not undergo surgical repair. METHODS: We carried out a cross-sectional analysis of patients with unoperated anomalous aortic origin of a coronary artery at our institution from 1 January, 2000 to 31 January, 2016. We prospectively assessed quality of life using standardised questionnaires. Medical records were reviewed for clinical and exercise stress test data. Statistical analyses were performed using Student's t-tests and Spearman's correlation coefficients. RESULTS: In total, 56 families completed the questionnaires. The average age at enrolment was 14.7+/-6 years. The majority were male (n=44, 78.6%) and had interarterial anomalous right coronary artery (n=38, 67.9%). Patients had normal quality of life on the PedsQL 4.0 Report, Child Health Questionnaire Child Form 87, and SF-36v2. Their parents had normal quality of life on the PedsQL 4.0 Parent Report, but parents of exercise-restricted patients had decreased Physical Functioning, General Health Perception, Emotional Impact on Parent, and Physical Summary scores (p<0.001-0.048) on the Child Health Questionnaire Parent Form 50. CONCLUSIONS: Patients with unoperated anomalous aortic origin of a coronary artery appear to have normal quality of life, but parents of exercise-restricted patients have decreased general health and emotional and physical quality of life scores. Improved counselling of families may be beneficial in this group. Future studies with more patients should evaluate quality of life and exercise performance over time. PMID- 27667029 TI - Investigation of the environmental impacts of municipal wastewater treatment plants through a Life Cycle Assessment software tool. AB - This paper investigates the total and per capita environmental impacts of municipal wastewater treatment in the function of the population equivalent (PE) with a Life Cycle Assessment (LCA) approach using the processes of the Ecoinvent 2.2 database available in the software tool SimaPro v.7.3. Besides the wastewater treatment plant (WWTP), the study also considers the sewerage system. The obtained results confirm that there is a 'scale factor' for the wastewater collection and treatment even in environmental terms, in addition to the well known scale factor in terms of management costs. Thus, the more the treatment plant size is, the less the per capita environmental impacts are. However, the Ecoinvent 2.2 database does not contain information about treatment systems with a capacity lower than 30 PE. Nevertheless, worldwide there are many sparsely populated areas, where it is not convenient to realize a unique centralized WWTP. Therefore, it would be very important to conduct an LCA study in order to compare alternative on-site small-scale systems with treatment capacity of few PE. PMID- 27667031 TI - Wound care in the community. AB - Primary health care forms an integral part both of the country's health care system and the overall social and economic development of the community. It is the first level of contact of individuals, the family and the community with the National Health Service, bringing healthcare as close as possible to where people live and work and constitutes the first elements of a continuing health care process ( 1 ). The increasing move away from hospital-centred services towards disease prevention and health promotion in the community is both evident and welcome. Successful community care services depend upon a review' of how health and social services are organised and managed, which should include a reorientation of many traditions in nursing and medicine. In addition to disease prevention and health-promotion, patients with acute or chronic illnesses also receive care, treatment and rehabilitation in the community, being referred for specialist service as necessary. PMID- 27667032 TI - Nursing world '91. AB - On behalf of the Royal College of Nursing, Nursing Standard and Lowndes Exhibition Organisers Ltd, I would like to welcome you to Nursing World '91. PMID- 27667033 TI - Comparing efficacies. AB - Comparative treatments with a hydrocolloid wound dressing and an antiseptic non adherent control dressing were evaluated in 27 patients. Thirteen patients in the study had leg ulcers, while14 had pressure sores. Measurements of wound improvement included use of a computerised photographic technique to assess changes in wound size. PMID- 27667030 TI - Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival. AB - TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity. PMID- 27667035 TI - Returning nurses tell of colleagues left behind. AB - Many British nurses are choosing to stay in the Gulf despite the constant threat of bombings, the first staff to leave Saudi Arabia since fighting broke out have revealed. PMID- 27667034 TI - Comparing efficacies. AB - place for up to seven days. Our approachkin North Manchester has been to look at "the efficacy of one hydrocolloid dressing (Comfeel Ulcer Dressing, Coloplast Ltd)in the hospital environment, and compare it with a group being treated with a non-adherent dressing (Betadine, Napp). PMID- 27667037 TI - Has compile specialist skills lists. AB - Health authorities were compiling lists of nurses with specialist skills last week as the first casualties arrived in Britain. PMID- 27667036 TI - Gulf casualties 'mean longer waiting lists'. AB - Hospitals preparing for Gulf casualties may have to pay the price of longer waiting lists, as non-urgent admissions are halted. PMID- 27667038 TI - ? AB - Metropolitan Line-Up: A special Nursing Standard promotion for the four Thames regions was marked by a reception for leading nurses and news trade representative sat the RUN headquarters in London recently. PMID- 27667039 TI - 9-9-5 per cent pay rise? AB - The Gulf War has further confused speculation that this year's nurses' pay rise may be pegged just below 10 per cent. PMID- 27667040 TI - Nurses' 'flexible working' demands blocked. AB - Nurses' flexible working demands are being blocked by their colleagues before reaching 'willing' personnel officers, an Equal Opportunities Commission investigation's initial findings have indicated. PMID- 27667042 TI - Using a wound assessment chart. AB - One of the fundamental requisites of a team is leadership. In hospital practice the leadership role has been assumed by the doctor, usually the consultant ( 1 ). However, nursing has inherited the role of major prescriber for the treatment of wounds with, unfortunately, little rationale being employed. PMID- 27667043 TI - Pressure on for prescribing powers. AB - Consumer pressure groups have thrown their weight behind the RCN-led campaign to give community nurses limited prescribing powers. PMID- 27667044 TI - Observation levels must be recorded. AB - The level of observation needed by patients should be determined and recorded at admission, Health Service Commissioner William Reid has warned. PMID- 27667045 TI - Caring for Romania appeal. AB - Pictured at last week's meeting are, left to right: Olivia Harrison, Baroness Cox, RCNGeneral Secretary Christine Hancock and Norah Casey. PMID- 27667046 TI - Transfer deal for Romanian Appeal. AB - The 'Caring for Romania Appeal' launched by Nursing Standardlast March has officially merged with the Romanian Angel Appeal, the charity launched by ex Beatle wives. PMID- 27667047 TI - Timetable set for 'third wave' Trusts. AB - The Government aims to get a third wave of NHS Trusts into operation by April 1993, Health Minister Virginia Bot-tomley confirmed in the Commons last week. PMID- 27667049 TI - ? PMID- 27667048 TI - Lack of library funding throws P2000 off course. AB - Poor library facilities are posing a serious threat to the success of Project 2000courses throughout England, a survey of13 colleges of nursing approved in theproject's first round has revealed. PMID- 27667050 TI - Health service urged to set up nurse 'banks'. AB - Staff recruitment agencies should be setup by health service managers to cut the cost of hiring temporary staff, a new report urges. PMID- 27667051 TI - 'Time for action' call on racism report. AB - A King's Fund report urging Government action on NHS racism sparked a 'no more talk - time for action' call from the RCN last week. PMID- 27667052 TI - Scholarship nurses will research abroad. AB - Twenty nurses will get the chance to carry out research as a result of scholarships awarded by the Florence Nightingale Committee. PMID- 27667054 TI - Regional study days 1991. AB - Due to the substantial and prolonged demand, the UK is now divided into North and South for study day purposes but the content of the programmes remains identical. Hella Reissmann organises the Northern Group and Judy Waterlow is responsible for the Southern Group. PMID- 27667056 TI - Shortfall in high blood pressure treatment. AB - Four out of five patients with moderate to severely high blood pressure may not be receiving treatment from their general practitioner, according to a report from the Office of Health Economics. PMID- 27667057 TI - Tobacco advertising a big threat to women? AB - Thirty-five thousand British women die each year through smoking-related illness but seven million young women continue to be exposed to cigarette advertising placed in magazines. PMID- 27667058 TI - Needs of post-therapy cancer patients. AB - Nurses must recognise and pay more attention to the needs of cancer patients who are recovering from their first line of therapy, an oncology clinical nurse specialist warned last week. PMID- 27667059 TI - New treatment hope for alcohol abuse. AB - Preliminary findings suggest that ri-tanserin might be a useful treatment in alcohol dependence. PMID- 27667061 TI - Preventing heat loss in neonatal units. AB - The possible thermal consequences of exterior windows should be considered when neonatal intensive care units are designed, a nurse researcher says. PMID- 27667060 TI - Dyslexia may be general learning deficiency. AB - Dyslexia might involve a general skill deficiency rather than merely difficulty with reading, researchers say. PMID- 27667062 TI - Brucellosis - a sexually transmitted disease? AB - Sexual partners of people infected with brucellosis should be monitored closely for evidence of infection, researchers say. PMID- 27667063 TI - Premature infants and car-seat positions. AB - Parents of premature infants should be made aware of the possible physiological effects of different positions in car seats. PMID- 27667064 TI - ? AB - None of us is really sure what shape the world will be come April 1 with the entrance of the purchaser-provider White Paper. I suppose for the majority of us things will feel no different. We will be expected to provide a service as in the past but this time we should know more about the quality and the cost. After the flurry of activity to get the contracts sorted out we will be entering a phase of ironing out the problems. PMID- 27667065 TI - Breaking the code. AB - When a nurse is found guilty of professional misconduct it stays on her or his career record for ten years and will almost certainly hinder that nurse's attempts to find a new job. PMID- 27667066 TI - Clinical directorates. AB - The term 'clinical directorate' is widely assumed to be modelled on experience since 1973 at the Johns Hopkins Hospital, Baltimore, USA. Involving doctors in budgeting and budget management, the system decentralises both revenue and expense budgeting. PMID- 27667067 TI - Going round in circles. AB - With today's fast-paced focus on quality, does anyone actually have time to stop the merry-go-round and assess exactly where it is they are going, what they want to achieve and whether they are being successful or not? PMID- 27667069 TI - Dysssy on the equator. AB - Last year I arrived in Lilongwe, capital city of Malawi, after a tortuous ten hour flight from London. I had been invited to this southern African country by the British Council to speak on several aspects of nursing including quality assurance and the setting of standards. After being graciously welcomed at Kamuzu International Airport I was taken to accommodation in the residential centre of Lilongwe near Kamuzu College of Nursing. PMID- 27667068 TI - Standard setting in practice. AB - Reynolds is a continuing care ward of 28 beds for elderly people. Acting Sister Jenny Banks and staff nurse Bernadine Perry have been involved in writing standards of care on their ward for the past year. Staff nurse lan Reid joined the ward this January. PMID- 27667070 TI - Norwegian standards. AB - I live in Stavangar, a town on the southwest coast of Norway, facing Britain and mostly known as the oil capital of Norway. We have a hospital of 690 beds, recently built, where I have worked for most of the time since graduating in1980. I worked as a ward sister for about five years and have recently taken up the post of assisant head nurse within the same orthopaedic unit. PMID- 27667071 TI - Quality assurance D Sale Quality assurance Macmillan Education 58pp L7.50 0-333 46405-2. AB - Quality Assurance, a readable and concise book, might have been more aptly entitled A Beginner's Guide to Quality Assurance. Its strength lies in Diana Sale's lack of presumption that the reader has or should have a basic knowledge of the subject. PMID- 27667073 TI - Network news. PMID- 27667072 TI - Quality assurance in nursing practice N Kemp Quality assurance in nursing practice and E Richardson Butterworth-Heinemann 116pp L9.95 0-7506-0019-5. PMID- 27667074 TI - Launch in to sales! AB - If you love nursing but hate the frustrations of modern health-care what do you do with your skills when you hang up your uniform? An option that many ex-medics explore is using their medical experience in a commercial career as a Medical Sales Representative. There are basically two industries which recruit nurses as trainee sales people: pharmaceuticals and hospital products and equipment. PMID- 27667076 TI - Enrolled nurse scapegoat shame. AB - It eleven and a half years as a nurse have taught me one thing, it's that if your face doesn't fit, you've had it. PMID- 27667075 TI - Clearing the confusion. AB - I am extremely surprised by your editorial in Nursing Standard January 16 1991, expressing confusion between the English National Board continuing education framework and the United Kingdom Central Council Post Registration Education and Practice Project proposals. PMID- 27667078 TI - Clues across. PMID- 27667077 TI - Lucky us. AB - I was delighted to see the letter, 'Squeaks of approval' (Nursing Standard January 9), from Bristol Polytechnic undergraduates. PMID- 27667079 TI - Not just a servant. AB - I read your editorial, 'Serving Whom?' (Nursing StandardJanuary 9) with annoyance, perhaps tinged with post-flu impatience. PMID- 27667080 TI - Playing an important role. AB - As a hospital chaplain, I try to keep up with reading the various magazines from other disciplines in the National Health Service, but I have to criticise your article, 'Supporting parents when their baby dies' (Nursing Standard, October31). PMID- 27667081 TI - Information exchange. AB - I am a community sister involved with Individual Performance Review and I would be interested to know if anyone is designed/adapted a form for use in their own department or unit. PMID- 27667083 TI - Further reading list. PMID- 27667082 TI - Dame Catherine Hall looks back on the life and work of a distinguished nurse. AB - Christine Brown was the epitome of all that is best in the nursing tradition. She had commitment, knowledge and skill to a high degree. She cared for and about people, her patients, her colleagues and her staff, and she gave of herself in responding to their needs. PMID- 27667084 TI - Understanding Child Sexual Maltreatment Understanding Child Sexual Maltreatment K C Faller SAGE 252pp L14.95 0-8039-3842-X [Formula: see text]. AB - Kathleen Faller has written several studies based on her work and research with sexually abused children and their families. PMID- 27667085 TI - Advanced Nursing and Health Care Research F McLaughlin and L Marascuilo Saunders 384pp L32.50 0-7216-3098-7 [Formula: see text]. AB - I was disappointed by Advanced Nursing and Health Care Research. Not that it's bad, it's just that as a new book, there was nothing new in it. So there is nothing in it that isn't covered as well or better in other more established texts. PMID- 27667087 TI - Drawing up the action plans. AB - Health authorities have started to compile lists of nurses with specialist skills who could be called up to deal with Gulf casualties arriving in British hospitals. PMID- 27667088 TI - Post traumatic stress disorder explained. AB - At first I felt euphoric... on a high... I had come through and it felt good just to be alive.' This reaction from the survior of a serious incident in which no one had been killed is typical of the initial reaction to narrowly escaping death or severe injury. PMID- 27667089 TI - Care of the bums patient. AB - While the average National Health Service ward may be used to dealing with minor burns and scalds, it is unlikely that the majority will have significant experience in dealing with major burns. PMID- 27667090 TI - Elevated First-Trimester Total Bile Acid is Associated with the Risk of Subsequent Gestational Diabetes. AB - The aim of the current study is to assess whether total bile acid (TBA) level in first trimester pregnancy is associated with gestational diabetes mellitus (GDM). Biochemical parameters including serum TBA of 742 pregnant women were collected within 12 weeks of gestation and compared. At 24-28th weeks of gestation, 75 g oral glucose tolerance test (OGTT) was performed. The perinatal data of 330 women were collected. The results demonstrated women with GDM (n = 268) had higher first-trimester serum levels of TBA compared with healthy subjects (n = 474) (2.3 +/- 1.4 MUmol/L vs. 1.9 +/- 1.0 MUmol/L, P < 0.001). TBA was independently associated with GDM [adjusted odds ratio (AOR), 1.38; 95% confidence interval (CI), 1.18-1.61, P < 0.001]. Compared to the first category of TBA, women in the highest category had a marked increase in risk for GDM (AOR, 7.72; 95% CI, 3.22 18.50, P < 0.001). In conclusion, higher first-trimester TBA levels, even within normal range, may help indicate increased risk of GDM. PMID- 27667091 TI - Parametric analysis of colony morphology of non-labelled live human pluripotent stem cells for cell quality control. AB - Given the difficulties inherent in maintaining human pluripotent stem cells (hPSCs) in a healthy state, hPSCs should be routinely characterized using several established standard criteria during expansion for research or therapeutic purposes. hPSC colony morphology is typically considered an important criterion, but it is not evaluated quantitatively. Thus, we designed an unbiased method to evaluate hPSC colony morphology. This method involves a combination of automated non-labelled live-cell imaging and the implementation of morphological colony analysis algorithms with multiple parameters. To validate the utility of the quantitative evaluation method, a parent cell line exhibiting typical embryonic stem cell (ESC)-like morphology and an aberrant hPSC subclone demonstrating unusual colony morphology were used as models. According to statistical colony classification based on morphological parameters, colonies containing readily discernible areas of differentiation constituted a major classification cluster and were distinguishable from typical ESC-like colonies; similar results were obtained via classification based on global gene expression profiles. Thus, the morphological features of hPSC colonies are closely associated with cellular characteristics. Our quantitative evaluation method provides a biological definition of 'hPSC colony morphology', permits the non-invasive monitoring of hPSC conditions and is particularly useful for detecting variations in hPSC heterogeneity. PMID- 27667092 TI - Reappraisal of effects of serum chemerin and adiponectin levels and nutritional status on cardiovascular outcomes in prevalent hemodialysis patients. AB - Although chemerin, an adipokine, increases the cardiovascular (CV) risk in obese people, it is associated with a survival advantage in incident hemodialysis (HD) patients. We explored the potential effects of chemerin on CV outcomes in prevalent HD patients. This prospective study included 343 prevalent HD patients. The composite outcome was the occurrence of CV events and death during follow-up. We used multivariate Cox regression analysis to test the predictive power of different chemerin and adiponectin levels and geriatric nutritional risk index (GNRI) for the outcomes. HD patients with higher chemerin levels (>=211.4 ng/mL) had a lower risk of CV events (adjusted hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.41-0.98) and composite CV outcome (adjusted HR, 0.67; 95% CI, 0.45-0.99) than those with lower chemerin levels (<211.4 ng/mL). When evaluating CV outcomes, we identified an interaction between chemerin levels and GNRI, but not between chemerin and adiponectin levels. The findings remained robust in the sensitivity analysis. Thus, in prevalent HD patients with negligible residual renal function, higher chemerin levels predict more favourable CV outcomes. PMID- 27667093 TI - Validation of osteoporosis risk assessment tools in middle-aged Thai women. AB - OBJECTIVES: To validate osteoporosis risk assessment tools in middle-aged Thai women. METHODS: A total of 1038 women who had bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry were reviewed. Clinical data were used to validate the diagnostic test performance of various osteoporosis risk assessment tools, including ABONE, FRAX(r), ORAI, OSIRIS, SCORE, SOFSURF, and OSTA. The following parameters were evaluated: sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy; those with 95% confidence interval (CI) of the receiver operator characteristics area under the curve (ROC-AUC) > 0.5 were considered statistically significant. RESULTS: The subjects had a mean age of 53.01 +/- 6.20 years and body mass index (BMI) of 23.98 +/- 3.38 kg/m2. Among the osteoporosis risk assessment tools being evaluated, the tools that had ROC-AUC >0.8 and 95% CI >0.5, and could predict osteoporosis at the femoral neck with high specificity of >75% and NPV of >90%, were FRAX(r) without BMD (ROC-AUC 0.83; 95% CI 0.73-0.93; specificity 99.90; NPV 98.89), SCORE (ROC-AUC 0.86; 95% CI 0.78-0.94; specificity 98.79; NPV 98.99), and OSTA (ROC-AUC 0.86; 95% CI 0.79-0.94; specificity 75.03; NPV 99.73). CONCLUSION: The prevalence of osteoporosis in the middle-aged Thai women attending Siriraj Menopause Clinic is 7.3% at the lumbar spine and/or femoral neck. FRAX(r) without BMD, SCORE, and OSTA have appropriate validity as tools for ruling out osteoporosis in these women. PMID- 27667096 TI - Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls. AB - AIMS/HYPOTHESIS: To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage. METHODS: 27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined. RESULTS: Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower-upper quartile]): autistic children - 6.60 nM (4.48-8.91) and 7.00 nM (5.51-8.55), and healthy controls - 6.82 nM (4.47-7.02) and 6.82 nM (5.84-8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81-8.52) versus 9.00 nM (8.41-10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged. CONCLUSIONS/INTERPRETATION: Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host-microbe homeostasis. PMID- 27667097 TI - Enhanced skin deposition and delivery of voriconazole using ethosomal preparations. AB - Despite its broad-spectrum antifungal properties, voriconazole has many side effects when administered systemically. The aim of this work was to develop an ethosomal topical delivery system for voriconazole and test its potential to enhance the antifungal properties and skin delivery of the drug. Voriconazole was encapsulated into various ethosomal preparations and the effect of phospholipid and ethanol concentrations on the ethosomes properties were evaluated. The ethosomes were evaluated for drug encapsulation efficiency, particle size and morphology and antifungal efficacy. Drug permeability and deposition were tested in rat abdominal skin. Drug encapsulation efficiency of up to 46% was obtained and it increased with increasing the phospholipid concentration, whereas the opposite effect was observed for the ethanol concentration. The ethosomes had a size of 420-600 nm and negative zeta potential. The particle size of the ethosomes increased by increasing their ethanol content. The ethosomes achieved similar inhibition zones against Aspergillus flavus at a 2-fold lower drug concentration compared with drug solution in dimethyl sulfoxide. The ex vivo drug permeability through rat abdominal skin was ~6-fold higher for the ethosomes compared with the drug hydroalcoholic solution. Similarly, the amount of drug deposited in the skin was higher for the ethosomes and was dependent on the ethanol concentration of the ethosomes. These results confirm that voriconazole ethosomal preparations are promising topical delivery systems that can enhance the drug antifungal efficacy and improve its skin delivery. PMID- 27667095 TI - Polysorbates prevent biofilm formation and pathogenesis of Escherichia coli O104:H4. AB - Escherichia coli biotype O104:H4 recently caused the deadliest E. coli outbreak ever reported. Based on prior results, it was hypothesized that compounds inhibiting biofilm formation by O104:H4 would reduce its pathogenesis. The nonionic surfactants polysorbate 80 (PS80) and polysorbate 20 (PS20) were found to reduce biofilms by >= 90% at submicromolar concentrations and elicited nearly complete dispersal of preformed biofilms. PS80 did not significantly impact in vivo colonization in a mouse infection model; however, mice treated with PS80 exhibited almost no intestinal inflammation or tissue damage while untreated mice exhibited robust pathology. As PS20 and PS80 are classified as 'Generally Recognized as Safe' (GRAS) compounds by the Food and Drug Administration (FDA), these compounds have clinical potential to treat future O104:H4 outbreaks. PMID- 27667094 TI - Smoothing a rugged protein folding landscape by sequence-based redesign. AB - The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as alpha1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics. PMID- 27667098 TI - Growth inhibitory and apoptosis-inducing effects of allergen-free Rhus verniciflua Stokes extract on A549 human lung cancer cells. AB - Evidence suggests that Rhus verniciflua Stokes (RVS) or its extract has the potential to be used for the treatment of inflammatory and neoplastic diseases. However, direct use of RVS or its extract as a herbal medicine has been limited due to the presence of urushiol, an allergenic toxin. In the present study, we prepared an extract of the allergen-removed RVS (aRVS) based on a traditional method and investigated its inhibitory effect on the growth of various types of human cancer cells, including lung (A549), breast (MCF-7) and prostate (DU-145) cancer cell lines. Notably, among the cell lines tested, treatment with the aRVS extract strongly inhibited proliferation of the A549 cells at a 0.5 mg/ml concentration for 24 h that was not cytotoxic to normal human dermal fibroblasts. Furthermore, aRVS extract treatment largely reduced the survival and induced apoptosis of the A549 cells. At the mechanistic levels, treatment with the aRVS extract led to the downregulation of Bcl-2 and Mcl-1 proteins, the activation of caspase-9/-3 proteins, an increase in cytosolic cytochrome c levels, the upregulation of Bax protein, an increase in phosphorylated p53 protein but a decrease in phosphorylated S6 protein in the A549 cells. Importantly, treatment with z-VAD-fmk, a pan-caspase inhibitor attenuated aRVS extract-induced apoptosis in the A549 cells. These results demonstrate firstly that aRVS extract has growth inhibitory and apoptosis-inducing effects on A549 human lung cancer cells through modulation of the expression levels and/or activities of caspases, Bcl-2, Mcl-1, Bax, p53 and S6. PMID- 27667100 TI - Morphology Controls on Calcite Recrystallization. AB - Environmental scientists and geoscientists working in different fields regard the reactivity of calcite and corresponding changes in its trace elemental- or isotopic composition from diametrically opposed points of view. As one extreme, calcite based environmental remediation strategies rely on the fast recrystallization of calcite and the concurrent uptake and immobilization of pollutants. Paleo-ecological investigations denote the other extreme, and rely on the invariability of calcite composition over geological periods of time. We use long-term radiotracer experiments to quantify recrystallization rates of seven types of calcite powder with diverse morphology and particle size distribution. On the one hand our results demonstrate the long-term metastability of calcite with equilibrated crystal surfaces even at isotopic dis-equilibrium. On the other hand, we document the extremely high reactivity and interfacial free energy of freshly ground, rough calcite. Our results indicate that bulk calcite recrystallization is an interfacial free energy driven Ostwald-ripening process, in which particle roughness effects dominate over the effect of crystal habitus and particle size. We confirm that the dynamic equilibrium exchange of crystal constituents between kink sites involves an activation barrier of about 25 kJ/mol. At room temperature the equilibrium exchange is limited to a near surface region and proceeds at a rate of (3.6 +/- 1.4).10-13 mol/(m2.s). PMID- 27667099 TI - Optimization of hierarchical structure and nanoscale-enabled plasmonic refraction for window electrodes in photovoltaics. AB - An ideal network window electrode for photovoltaic applications should provide an optimal surface coverage, a uniform current density into and/or from a substrate, and a minimum of the overall resistance for a given shading ratio. Here we show that metallic networks with quasi-fractal structure provides a near-perfect practical realization of such an ideal electrode. We find that a leaf venation network, which possesses key characteristics of the optimal structure, indeed outperforms other networks. We further show that elements of hierarchal topology, rather than details of the branching geometry, are of primary importance in optimizing the networks, and demonstrate this experimentally on five model artificial hierarchical networks of varied levels of complexity. In addition to these structural effects, networks containing nanowires are shown to acquire transparency exceeding the geometric constraint due to the plasmonic refraction. PMID- 27667101 TI - [Interpretation of Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease (GOLD) 2016]. PMID- 27667102 TI - [Evaluation of the efficacy of laparoscopic surgery in treatment of advanced mid low rectal cancer following a long-term neoadjuvant chemoradiotherapy]. AB - Objective: To explore the efficacy of laparoscopic surgery in treatment of advanced mid-low rectal cancer following a long-term neoadjuvant chemoradiotherapy. Methods: Clinicopathologic and perioperative data were collected retrospectively from 74 patients with advanced mid-low rectal cancer, who received both neoadjuvant chemoradiotherapy and resections between January 2010 and January 2013 at Xinjiang tumor hospital. Routine follow-up was conducted. The safety and long-term survival of 36 patients who underwent laparoscopic resection were compared with those of 38 patients who received conventional resection. Results: The laparoscopic group had less amount of blood loss during surgery (50 ml vs 100 ml, P<0.05). The time needed for recovery of gastrointestinal function in the laparoscopic group was significantly shorter than that in the open surgery group (2.0 d vs 3.0 d, P<0.05). The rate of postoperative complication was 19.4% and 42.1% (P<0.05), respectively. In terms of the range of radical surgery and the numbers of dissected lymph nodes (8 and 10, P>0.05), no significant difference were found in the two groups. The operation duration and hospital stay in the laparoscopic group was longer than that in the open surgery group (240.0 min vs 231.5 min , P>0.05) (22.0 d vs 21.5 d , P>0.05), but no significant difference was found between the two groups. There were no significant difference in the incidence of 3 disease-free survival rate (53.0% vs 43.8%, P>0.05) and overall survival rate (70.0% vs 62.9%, P>0.05) between two groups. Conclusion: Laparoscopic surgery is a safe and feasible option for advanced mid-low rectal cancer patients who undergone the neoadjuvant chemoradiotherapy because of the similar rate of radical resection and satisfied long-term outcomes, which will have a better prospect in the future. PMID- 27667103 TI - [Application of new chest holder in the median sternotomy for open heart surgery in adults]. AB - Objective: To explore the application of new chest holder in the median sternotomy for open heart surgery in adults. Methods: Two hundred adult patients in Henan Provincial People's Hospital from May 2013 to May 2015 were enrolled in the study and randomly divided into two groups. Experimental group included 100 cases who accepted the new type of chest holder in the open heart surgery. Control group were also composed of 100 cases whose sternums were fixed with the pure steel wire cerclage. Sternal closure time was recorded since the sternum closing. All subjects were followed up to obtain the chest incision healing, the incidence of sternal dehiscence, infection and secondary thoracotomy, and thus to estimated the effect of new chest holder. Results: All patients in the experimental group reached the effect of firm closed chest surgery. Sternal closure time of experimental group was much shorter than that of control group[(10+/-2) vs (21+/-4) min, P<0.001]. No sternal instability, dehiscence, infection and secondary thoracotomy were found during the follow-up. However, in the control group, 3 secondary thoracotomy cases, 6 sternal dehiscence cases and 2 sternal infection cases were detected. Conclusions: New type of chest holder in the median sternotomy for open heart surgery is more convenient with small surgical trauma. It can also effectively reduce the incidence of sternal instability, dehiscence, infection and secondary thoracotomy. PMID- 27667104 TI - [Association between hand-foot skin reaction and effectiveness of vascular endothelial growth factor receptor tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma]. AB - Objective: To investigate the association between hand-foot skin reaction (HFSR) in the treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and the effectiveness of VEGFR-TKIs. Methods: Clinical data of 155 patients with metastatic renal cell carcinoma (mRCC) treated with VEGFR-TKIs at the Cancer Hospital of Chinese Academy of Medical Sciences between January 2006 and January 2014 were retrospectively analyzed. All the patients received first-line VEGFR-TKI therapy. The treatment effectiveness and outcome between patients developing HFSR and those without HFSR were compared. Comparison of treatment response rate (RR) was performed with chi2 test, survival analysis was performed using Kaplan-Meier method, with a significance level of 0.05. Results: The median survival of all the 155 patients was 36.2 months. Among the 117 (75.5%) patients who developed HFSR, 19 patients (12.3%) had grade I HFSR, 73 (47.1%) had grade II, and 25 (16.1%) had grade III; there were no grade IV events. The RR and median progression-free survival (mPFS) in patients who did not develop HFSR were 15.8% and 6.7 months, respectively; while the RR and mPFS in patients who developed HFSR were 52.1% and 13.8 months, respectively (P<0.001, P=0.002). The RR and mPFS in patients with grade I HFSR were 42.1% and 9.5 months, respectively; those in patients with grade II HFSR were 56.2% and 12.2 months, respectively, in patients with grade III were 48.0% and 22.2 months, respectively, with statistically significant differences among the three grades of HFSR (P=0.001, 0.009). Conclusions: HFSR might be an effective predictor for effectiveness of VEGFR-TKIs in mRCC patients. Large-sample studies are warranted to further prove these results. PMID- 27667105 TI - [Application of laparoscopic transection of median hepatic fissure in difficult laparoscopic liver resections]. AB - Objective: The aim was to explore the strategy and clinical value of laparoscopic transection of median hepatic fissure (MHF) in difficult laparoscopic liver resections. Methods: First the MHF was located and marked, then the transection plane of the MHF was set. Next, the laparoscopic Multifuctional Operative Dissector (LPMOD) and the technique of curettage and aspiration were utilized to transect the liver beginning from the middle portion of the gallbladder fossa, in a caudal-to-cranial and anterior-to-posterior direction, until the clear exposure of the anterior surface of the intrahepatic inferior vena cava. Transection of the MHF was accurately achieved. Finally, dissection of the second and third porta hepatis were carefully performed and mobilization of the transected liver was achieved. This technique of laparoscopic transection of MHF was successfully performed in 13 patients in difficult laparoscopic liver resections. Results: Between April 2014 and August 2015, 13 patients received the technique of laparoscopic transection of MHF in difficult laparoscopic liver resections, including 10 cases of laparoscopic right hepatectomy, two cases of laparoscopic left hepatectomy and one case of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The maximum size of the transected tumor was 15 centimeter. Duration of surgery was 240-430 min[Mean, 324.4+/-50.0]; the time for transection of the MHF was 40-118 min[mean, 66.4+/-22.7]. Blood loss was 200-2 000 ml[583.3+/-452.9]. The length of postoperative hospital stay was 6-25 days[mean, 13.2+/-5.2]. Seven patients received intraoperative transfusions. No postoperative intraabdominal bleeding, liver failure or other severe postoperative complications occurred. No perioperative death occurred. Conclusions: Application of laparoscopic transection of the MHF in difficult laparoscopic liver resections can help to clearly expose the second and third porta hepatis, especially in patients who have huge tumors and poor exposure for hepatic dissection. Moreover, precise location and transection of the MHF remains very important strategies of applying this technique. PMID- 27667106 TI - [Microsurgery treatment of midline deep brain lesions (clinical analysis of 25 cases)]. AB - Objective: To explore experience and methods in the microsurgical treatment of midline deep brain lesions. Methods: The clinical data of patients with midline deep brain lesions were retrospectively analyzed. The clinical manifestation, imaging findings, lesion locations, surgical procedures, pathological diagnosis and follow-up results were summarized and analyzed. All the lesions were located deeply in the brain midline: corpus callosum (n=1), thalamus and basal ganglia (n=6), lateral ventricle (n=4), the third ventricle (n=2), pineal region (n=8), brainstem and fourth ventricle region (n=4). Results: Symptoms of 25 cases improved to varying degrees after operation and all the lesions got gross total removal without perioperative death. Followed by necessary adjuvant radiotherapy and/or chemotherapy, there were no recurrence during the follow-up period. Conclusions: Suitable surgical approaches should be individually chosen according to lesion location, the surrounding neural and vascular anatomy, blood supply, the patient's medical condition and the operator's experience. Localization of minor lesions can be assisted by neuronavigation system. In addition to try to determine the border of the lesion during operation, we emphasize the protection of the surrounding vital neural structures and deep veins. Finally, adjuvant radiotherapy and/or chemotherapy based on histology should be adopted to prevent recurrence. PMID- 27667107 TI - [Effect of moluodan on gastric secretion in atrophic gastritis rats]. AB - Objective: To investigate the effect of moluodan on gastric secretion and the underlying mechanism of moluodan in treating atrophic gastritis. Method: According to the random number table, 120 healthy male specific-pathogen-free (SPF) Sprague-Dawley rats were divided into 4 groups: control group, model group, moluodan low-dose group, and moluodan high-dose group, with 30 rats in each group. The control group was administered with normal saline 2 ml/d by gavage, the other three groups were administered with 2% sodium salicylate 1 ml/d, 20 mol/L sodium deoxycholate 1 ml/d, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) 200 mg/kg for every 10 days. And 16 weeks later, the control group and model group were treated with normal saline 2 ml/d by gavage, meanwhile the moluodan low-dose group was treated with moluodan 0.9 g.kg-1.d-1and the high-dose group was treated with moluodan 1.8 g.kg-1.d-1, continuously for 12 weeks. Ten rats of each group were sacrificed at the end of 4, 8, 12 weeks. The effect of moluodan on atrophic gastritis was observed. The secretion function of gastric mucosa was assessed through detecting the numbers of gastrin-secreting cells (G cells) and somatostatin-secreting cell (D cells) in gastric mucosa using immunochemical staining, and measuring the serum levels of gastrin (GAS) and somatostatin (SS) using enzyme-linked immunosorbent assay (ELISA). Results: After 8 weeks, the numbers of G and D cells in gastric mucosa in the moluodan high-dose group significantly increased compared with the model group[(0.617+/-0.114) vs (0.476+/ 0.116) cells/mm2, (0.504+/-0.084) vs (0.369+/-0.148) cells/mm2, both P<0.05]; the numbers of G and D cells in gastric mucosa in the low-dose group increased after 12-week's treatment[(0.674+/-0.129) vs (0.528+/-0.103) cells/mm2, (0.526+/-0.087) vs (0.371+/-0.058) cells/mm2, both P<0.05]. The serum GAS levels increased markedly after 8 weeks in the moluodan high-dose group and after 12 weeks in the low-dose group[(1.313+/-0.080) ng/ml vs (0.964+/-0.080) ng/ml, (1.202+/-0.124) ng/ml vs (0.909+/-0.054) ng/ml, both P<0.01]; the serum SS levels in both high- and low-dose groups were significantly lower than in the model group after 8 week's treatment[(2.376+/-0.199) ng/ml, (2.238+/-0.155) ng/ml vs (2.605+/-0.183) ng/ml, both P<0.05]. Conclusion: Moluodan may treat atrophic gastritis by repairing G and D cells in gastric mucosa and thus increasing serum levels of GAS. PMID- 27667108 TI - [Role of endoplasmic reticulum stress-mediated glycogen synthase kinase 3beta activity in pathogenesis of acute liver failure in mice]. AB - Objective: To study the role of endoplasmic reticulum (ER) stress-mediated glycogen synthase kinase 3beta (GSK3beta) activity in the pathological process of liver injury in acute liver failure (ALF) mice. Methods: ALF model was established by intraperitoneal injection of D-galactosamine/lipopolysaccharide (D GalN/LPS) in C57BL/6 mice. The mice were divided into control group (n=10), ALF model group (n=18), 4-phenylbutyrate (4-PBA, an ER stress inhibitor) group (n=18) and SB216763 (a specific inhibitor of GSK3beta) group (n=16). The serum alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured to reflect the liver function, liver injury was assessed by observing pathological changes of liver tissue, the levels of proteins in liver tissue were analyzed by Western blotting, the activity of GSK3beta in liver tissue was detected using GSK3beta activity assay kit, and the survival rate of hepatocyte was measured by methyl thiazolyl tetrazolium (MTT) assay. Results: In in vivo experiment, the expression levels of ER stress markers, glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP), were upregulated during the progression of D-GalN/LPS-induced ALF, indicating activation of severe ER stress and increased activity of GSK3beta. Compared with the model group, inhibition of ER stress by 4-PBA improved liver function[ALT: (365.4+/-58.6) U/L vs (1 094.5+/-201.5) U/L, P<0.05; AST: (555.1+/-60.8) U/L vs (1 444.3+/-533.7) U/L, P<0.05)and pathological injury, also decreased the activity of GSK3beta (2.6+/-0.3 vs 4.6+/-1.3, P<0.05). Inhibition of GSK3beta activity was shown to alleviate liver injury in ALF by reducing the expression levels of GRP78 and CHOP. The in vitro experiment of tunicamycin-induced hepatocyte apoptosis showed that inhibition of GSK3beta activity increased the cell survival rate. Conclusion: In ALF induced by D-GalN/LPS, severe ER stress may accelerate the development and progress of ALF by upregulating the activity of GSK3beta. PMID- 27667109 TI - [Endoplasmic reticulum stress in INS-1-3 cell associated with the expression changes of MODY gene pathway]. AB - Objective: To profile the gene expression changes associated with endoplasmic reticulum stress in INS-1-3 cells induced by thapsigargin (TG) and tunicamycin (TM). Methods: Normal cultured INS-1-3 cells were used as a control. TG and TM were used to induce endoplasmic reticulum stress in INS-1-3 cells. Digital gene expression profiling technique was used to detect differentially expressed gene. The changes of gene expression were detected by expression pattern clustering analysis, gene ontology (GO) function and pathway enrichment analysis. Real time polymerase chain reaction (RT-PCR) was used to verify the key changes of gene expression. Results: Compared with the control group, there were 57 (45 up regulated, 12 down-regulated) and 135 (99 up-regulated, 36 down-regulated) differentially expressed genes in TG and TM group, respectively. GO function enrichment analyses indicated that the main enrichment was in the endoplasmic reticulum. In signaling pathway analysis, the identified pathways were related with endoplasmic reticulum stress, antigen processing and presentation, protein export, and most of all, the maturity onset diabetes of the young (MODY) pathway. Conclusion: Under the condition of endoplasmic reticulum stress, the related expression changes of transcriptional factors in MODY signaling pathway may be related with the impaired function in islet beta cells. PMID- 27667110 TI - [Expression changes of aldehyde dehydrogenase 1A1 in rat cryptorchidism and normal testis]. AB - Objective: To study the mRNA and protein expression of aldehyde dehydrogenase 1A1(ALDH1A1)in rat cryptorchidism and normal testis. Methods: We established the cryptorchidism model by flutamide and took normal testis as normal group.The testicular tissue samples were collected on 15 days, 45 days, and 90 days after birth respectively.The expression of ALDH1A1 in rat cryptorchidism and normal testis were investigated by real-time PCR, Western blot and immunohistochemisty intissue microarray. Results: The mRNA expression of ALDH1A1 in cryptorchidism group in infant, adolescent and adult period were 1.01+/-0.19, 1.60+/-0.32, 0.75+/-0.16, and 1.66+/-0.23, 0.52+/-0.08, 0.15+/-0.10 in normal group, respectively.The expression of ALDH1A1 in cryptorchidism group was significantly lower than that in normal group in infant period, but it was significantly higher than that in the normal group in adolescent and adult period(P<0.05). Conclusions: The expression of ALDH1A1 was different in different age period during the process of testicular development of rat. It showed an important relationship between ALDH1A1 and cryptorchidism. PMID- 27667111 TI - [Analyzing the status of depression and anxiety of new registered tuberculosis outpatients and correlations with social support influence factors]. AB - Objective: To investigate the prevalence of depression and anxiety and the related factors among new registered tuberculosis (TB) outpatients. Methods: Questionnaire survey was conducted in 1 105 new registered TB patients from sixteen districts of Beijing city during Jan to Jun, 2015. Structured self administered questionnaire including gender, age, education, occupation, history of smoking and drinking information was designed by epidemiological and psychiatric experts from Beijing Research Institute for Tuberculosis Control. Meanwhile the TB patients status including depression, anxiety and social supporting were investigated by using Self-rating Depression Scale (SDS), Self Rating Anxiety Scale (SAS) and Social Support Rating Scale (SSRS). The survey data was then analyzed. A total of 1 132 questionnaires were issued and 1 119 were recovered including 1 105 valid questionnaires, and the effective rate was 98.7%. Results: There were 742 males and 363 females among 1 105 new registered TB patients. Age ranged from 16 to 65 years, the mean age was (35.7+/-13.8) years old. The total standard scores of SDS and SAS were (45.00+/-12.40) and (39.46+/ 10.03) points, obviously higher than those in national norms (all P<0.05). The detection rates of depression and anxiety were 29.8% (329/1 105) and 13.5% (149/1 105). Multivariate Logistic regression analysis showed that TB patients with female (OR=1.75, 95% CI: 1.32-2.30), over 35 years (OR=1.82, 95% CI: 1.39-2.39), annual household income <50 000 ? (OR=1.57, 95% CI: 1.19-2.06), rarely talking to someone about their worries (OR=1.41, 95% CI: 1.05-1.90) had high risk of depression (all P<0.05). Annual household income<50 000 ? (OR=1.69, 95% CI: 1.17 2.43), rarely talking to someone about their worries (OR=1.80, 95% CI: 1.19-2.74) also had high risk of anxiety (all P<0.05). The medians scores in social support, subjective support, objective support and support utilization were 38(32, 43), 22(18, 26), 8(6, 10) and 7 (6, 9) points, respectively, and these scores were negatively related to depression and anxiety. Conclusion: Depression and anxiety prevalence in TB patients are obviously higher than those in normal people, and there are many factors that can cause or contribute to depression and anxiety. PMID- 27667112 TI - Non-vitamin K oral anticoagulants versus vitamin K antagonists in the treatment of venous thromboembolic disease. AB - INTRODUCTION: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the western world. The approval of non-vitamin K oral anticoagulants (NOACs) as antithrombotic alternatives to vitamin K antagonists (VKAs) has offered more treatment options to physicians for the prevention of VTE recurrence, fatal pulmonary embolism (PE) and long-term complications. Four NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) that have been approved for the treatment of acute VTE following large phase III trials, where NOACs demonstrated similar efficacy and superior safety profile compared to VKAs. AREAS COVERED: The purpose of this review article is to summarise current knowledge of oral anticoagulation for the treatment of acute VTE and to compare NOACs with VKAs, highlighting the factors that might influence the decisions of physicians. Data for this article were obtained through a search of PubMed for trials comparing NOACs with VKAs in acute VTE setting and articles or analyses that interpreted results from these trials. EXPERT OPINION: The NOACs have changed clinical practice regarding oral anticoagulation for acute VTE. Despite their advantages, 'grey zones' still remain and more studies are needed to provide evidence and confirm the superiority (or at least non-inferiority) of NOACs over VKAs. Real world data might give additional insights. PMID- 27667114 TI - Corrigendum. PMID- 27667113 TI - Corrigendum. PMID- 27667115 TI - The development and evaluation of a non-pressurised, chemical oxygen reaction generation vessel and breathing system providing emergency oxygen for an extended duration. AB - The objective was to develop a sodium percarbonate/water/catalyst chemical oxygen generator that did not require compressed gas. Existing devices utilising this reaction have a very short duration of action. Preliminary experiments with a glass reaction vessel, water bath and electronic flowmeter indicated that many factors affected oxygen production rate including reagent formulation, temperature, water volume and agitation frequency. Having undertaken full-scale experiments using a stainless steel vessel, an optimum combination of reagents was found to be 1 litre water, 0.75 g manganese dioxide catalyst, 60 g sodium percarbonate granules and 800 g of custom pressed 7.21 (0.28) g sodium percarbonate tablets. This combination of granules and slower dissolution tablets produced a rapid initial oxygen flow to 'purge' an attached low-flow breathing system allowing immediate use, followed by a constant flow meeting metabolic requirements for a minimum of 1 h duration. PMID- 27667116 TI - Aliskiren targets multiple systems to alleviate cancer cachexia. AB - To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia-associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia-induced activation of the renin-angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy lysosome as well as ubiquitin-proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti-cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin proteasome pathway (UPP). PMID- 27667117 TI - Rh-Catalyzed Conjugate Addition of Arylzinc Chlorides to Thiochromones: A Highly Enantioselective Pathway for Accessing Chiral Thioflavanones. AB - A highly efficient asymmetric synthesis of chiral thioflavanones is developed via conjugate addition of arylzinc reagents to thiochromones using Rh(COD)Cl2/(R) 3,4,5-MeO-MeOBIPHEP catalyst. This method overcomes catalyst poisoning and substrate inertness and affords a series of chiral thioflavanones (2 arylthiochroman-4-ones) in good yields (up to 91% yield) with excellent ee values (up to 97% ee). The established asymmetric synthesis paves the way for further pharmaceutical studies. PMID- 27667118 TI - RE: 'Orthopaedic trauma patients and smoking: Knowledge deficits and interest in quitting'. PMID- 27667119 TI - Validation of international trauma scoring systems in urban trauma centres in India. AB - INTRODUCTION: In the Lower-Middle Income Country setting, we validate trauma severity scoring systems, namely Injury Severity Score (ISS), New Injury Severity Scale (NISS) score, the Kampala Trauma Score (KTS), Revised Trauma Score (RTS) score and the TRauma Injury Severity Score (TRISS) using Indian trauma patients. PATIENTS AND METHODS: From 1 September 2013 to 28 February 2015, we conducted a prospective multi-centre observational cohort study of trauma patients in four Indian university hospitals, in three megacities, Kolkata, Mumbai and Delhi. All adult patients presenting to the casualty department with a history of injury and who were admitted to inpatient care were included. The primary outcome was in hospital mortality within 30-days of admission. The sensitivity and specificity of each score to predict inpatient mortality within 30days was assessed by the areas under the receiver operating characteristic curve (AUC). Model fit for the performance of individual scoring systems was accomplished by using the Akaike Information criterion (AIC). RESULTS: In a registry of 8791 adult trauma patients, we had a cohort of 7197 patients eligible for the study. 4091 (56.8%)patients had all five scores available and was the sample for a complete case analysis. Over a 30-day period, the scores (AUC) was TRISS (0.82), RTS (0.81), KTS (0.74), NISS (0.65) and ISS (0.62). RTS was the most parsimonious model with the lowest AIC score. Considering overall mortality, both physiologic scores (RTS, KTS) had better discrimination and goodness-of-fit than ISS or NISS. The ability of all Injury scores to predict early mortality (24h) was better than late mortality (30day). CONCLUSION: On-admission physiological scores outperformed the more expensive anatomy-based ISS and NISS. The retrospective nature of ISS and TRISS score calculations and incomplete imaging in LMICs precludes its use in the casualty department of LMICs. They will remain useful for outcome comparison across trauma centres. Physiological scores like the RTS and KTS will be the practical score to use in casualty departments in the urban Indian setting, to predict early trauma mortality and improve triage. PMID- 27667120 TI - What Justifies a Future with Humans in It? AB - Antinatalist commentators recommend that humanity bring itself to a close, on the theory that pain and suffering override the value of any possible life. Other commentators do not require the voluntary extinction of human beings, but they defend that outcome if people were to choose against having children. Against such views, Richard Kraut has defended a general moral obligation to people the future with human beings until the workings of the universe render such efforts impossible. Kraut advances this view on the grounds that we are obliged to exercise beneficence toward others and on the grounds that the goods available in human lives are morally compelling. This account ultimately succeeds in making no more than a prima facie defense of human perpetuation because considerations of beneficence could override - in some cases probably should - override any duty to perpetuate human beings. While the goods of human life may be distinctive, they cannot serve as reason-giving in regard to their own perpetuation. Ironically, the exercise of beneficence may authorize the extinction of human beings, if it becomes possible to enhance the goods available to human descendants in a way that moves them away from human nature as now given. The defense of a morally obligatory and strictly human future remains elusive, even as it becomes morally desirable to work against Fateful Catastrophes, those human-caused events that threaten to extinguish existing lives already good and enriching for their bearers. PMID- 27667121 TI - Differences in atrial fibrillation-associated proteins between the left and right atrial appendages from patients with rheumatic mitral valve disease: A comparative proteomic analysis. AB - The majority of proteomic studies have focused on identifying atrial fibrillation (AF)-associated proteins in the right atrium (RA), thus potential differences in AF-associated proteins between the RA and left atrium (LA) remain unknown. The aim of the present study was to perform proteomic analysis to compare the potential differences in AF-associated proteins between the right atrial appendage (RAA) and left atrial appendage (LAA) in patients with rheumatic mitral valve disease (RMVD). RAA and LAA tissues were obtained from 18 patients with RMVD (10 with AF) during mitral valve replacement surgery. Two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) proteomics analysis was performed using these tissues to identify AF-associated proteins in RAA and LAA. Subsequently, the proteomics data was validated using western blot analysis of nine selected proteins. In RAA, 32 AF-associated proteins were significantly dysregulated (15 upregulated and 17 downregulated). In LAA, 31 AF-associated proteins were significantly dysregulated (13 upregulated and 18 downregulated). Among these AF-associated proteins, 17 were AF-associated in both RAA and LAA, 15 were AF-associated only in RAA, and 14 were AF-associated only in LAA. Amongst the differentially expressed proteins, western blot analysis validated the results for 6 AF-associated proteins, and demonstrated similar distributions in RAA and LAA compared with the 2-D DIGE results. Of these proteins, 2 proteins were AF-associated in both RAA and LAA, 2 were AF-associated only in RAA, and 2 were AF-associated only in LAA. Additionally, the different distributions of AF associated proteins in the RAA and LAA of patients with RMVD was analyzed, which may reflect the different regulatory mechanisms of the RA and LA in AF. These findings may provide new insights into the underlying molecular mechanisms of AF in patients with RMVD. PMID- 27667122 TI - Deletions Overlapping VCAN Exon 8 Are New Molecular Defects for Wagner Disease. AB - Wagner disease is a rare nonsyndromic autosomal-dominant vitreoretinopathy, associated with splice mutations specifically targeting VCAN exon 8. We report the extensive genetic analysis of two Wagner probands, previously found negative for disease-associated splice mutations. Next-generation sequencing (NGS), quantitative real-time PCR, and long-range PCR identified two deletions (3.4 and 10.5 kb) removing at least one exon-intron boundary of exon 8, and both correlating with an imbalance of VCAN mRNA isoforms. We showed that the 10.5-kb deletion occurred de novo, causing somatic mosaicism in the proband's mother who had an unusually mild asymmetrical phenotype. Therefore, exon 8 deletions are novel VCAN genetic defects responsible for Wagner disease, and VCAN mosaic mutations may be involved in the pathogenesis of Wagner disease with attenuated phenotype. NGS is then an effective screening tool for genetic diagnosis of Wagner disease, improving the chance of identifying all disease-causative variants as well as mosaic mutations in VCAN. PMID- 27667123 TI - Spiral counter-current chromatography: Design, development, application, and challenges. AB - Depending on the rapid growth in the radial gradient of the centrifugal force, spiral counter-current chromatography can greatly improve the retention of stationary phase, especially for the aqueous two-phase systems with ultra-polar and high viscosity that are not well retained in the conventional multilayer coils counter-current chromatography. As a result, it is an attractive and alternative technology that is suited for separation of hydrophilic compounds and has led to many exciting progress in recent years. This review presents the recent advances and applications of spiral counter-current chromatography, including its major benefits and limitations, some novel methods to improve the separation efficiency and its applications in separation of real samples. In addition, the remaining challenges and future perspectives on development of spiral counter-current chromatography also are proposed in this article. PMID- 27667124 TI - Hypoxia augments MHC class I antigen presentation via facilitation of ERO1-alpha mediated oxidative folding in murine tumor cells. AB - To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer-specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here, we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen specific CTLs by tumor cells that had been pre-incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre-incubated under a condition of normoxia. Cell surface expression of MHC class I-peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs. We show that the hypoxia-inducible ER resident oxidase ERO1-alpha plays an important role in the hypoxia-induced augmentation of MHC class I-peptide complex expression. ERO1-alpha facilitated oxidative folding of MHC class I heavy chains, thereby resulting in the augmentation of cell surface expression of MHC class I-peptide complex under hypoxic conditions. These results suggest that since the expression of MHC class I-peptide complex is augmented in a hypoxic tumor microenvironment, strategies for inhibiting the function of regulatory T cells and myeloid-derived suppressor cells and/or immunotherapy with immune checkpoint inhibitors are promising for improving cancer immunotherapy. PMID- 27667126 TI - Abdominal pannus with verrucous nodules, ecchymosis, and ulcerations in the setting of lymphedema. PMID- 27667125 TI - The role of electrostatics in TrxR electron transfer mechanism: A computational approach. AB - Thioredoxin reductase (TrxR) is an important enzyme in the control of the intracellular reduced redox environment. It transfers electrons from NADPH to several molecules, including its natural partner, thioredoxin. Although there is a generally accepted model describing how the electrons are transferred along TrxR, which involves a flexible arm working as a "shuttle," the molecular details of such mechanism are not completely understood. In this work, we use molecular dynamics simulations with Poisson-Boltzmann/Monte Carlo pKa calculations to investigate the role of electrostatics in the electron transfer mechanism. We observed that the combination of redox/protonation states of the N-terminal (FAD and Cys59/64) and C-terminal (Cys497/Selenocysteine498) redox centers defines the preferred relative positions and allows for the flexible arm to work as the desired "shuttle." Changing the redox/ionization states of those key players, leads to electrostatic triggers pushing the arm into the pocket when oxidized, and pulling it out, once it has been reduced. The calculated pKa values for Cys497 and Selenocysteine498 are 9.7 and 5.8, respectively, confirming that the selenocysteine is indeed deprotonated at physiological pH. This can be an important advantage in terms of reactivity (thiolate/selenolate are more nucleophilic than thiol/selenol) and ability to work as an electrostatic trigger (the "shuttle" mechanism) and may be the reason why TrxR uses selenium instead of sulfur. Proteins 2016; 84:1836-1843. (c) 2016 Wiley Periodicals, Inc. PMID- 27667127 TI - Bessel-beam illumination in dual-axis confocal microscopy mitigates resolution degradation caused by refractive heterogeneities. AB - One of the main challenges for laser-scanning microscopy of biological tissues with refractive heterogeneities is the degradation in spatial resolution that occurs as a result of beam steering and distortion. This challenge is particularly significant for dual-axis confocal (DAC) microscopy, which achieves improved spatial-filtering and optical-sectioning performance over traditional confocal microscopy through off-axis illumination and collection of light with low-numerical aperture (NA) beams that must intersect precisely at their foci within tissues. DAC microscope image quality is sensitive to positional changes and distortions of these illumination- and collection-beam foci. Previous studies have shown that Bessel beams display improved positional stability and beam quality than Gaussian beams when propagating through tissues with refractive heterogeneities, which suggests that Bessel-beam illumination may enhance DAC microscopy of such tissues. Here, we utilize both Gaussian and Bessel illumination in a point-scanned DAC microscope and quantify the resultant degradation in resolution when imaging within heterogeneous optical phantoms and fresh tissues. Results indicate that DAC microscopy with Bessel illumination exhibits reduced resolution degradation from microscopic tissue heterogeneities compared to DAC microscopy with conventional Gaussian illumination. PMID- 27667128 TI - Identification of key genes involved in polysaccharide bioflocculant synthesis in Bacillus licheniformis. AB - The present study reports the sequenced genome of Bacillus licheniformis CGMCC 2876, which is composed of a 4,284,461 bp chromosome that contains 4,188 protein coding genes, 72 tRNA genes, and 21 rRNA genes. Additional analysis revealed an eps gene cluster with 16 open reading frames. Conserved Domains Database analysis combined with qPCR experiments indicated that all genes in this cluster were involved in polysaccharide bioflocculant synthesis. Phosphoglucomutase and UDP glucose pyrophosphorylase were supposed to be key enzymes in polysaccharide secretion in B. licheniformis. A biosynthesis pathway for the production of polysaccharide bioflocculant involving the integration of individual genes was proposed based on functional analysis. Overexpression of epsDEF from the eps gene cluster in B. licheniformis CGMCC 2876 increased the flocculating activity of the recombinant strain by 90% compared to the original strain. Similarly, the crude yield of polysaccharide bioflocculant was enhanced by 27.8%. Overexpression of the UDP-glucose pyrophosphorylase gene not only increased the flocculating activity by 71% but also increased bioflocculant yield by 13.3%. Independent of UDP-N-acetyl-D-mannosamine dehydrogenase gene, flocculating activity, and polysaccharide yield were negatively impacted by overexpression of the UDP-N acetylglucosamine 2-epimerase gene. Overall, epsDEF and gtaB2 were identified as key genes for polysaccharide bioflocculant synthesis in B. licheniformis. These results will be useful for further engineering of B. licheniformis for industrial bioflocculant production. Biotechnol. Bioeng. 2017;114: 645-655. (c) 2016 Wiley Periodicals, Inc. PMID- 27667130 TI - Breed differences of bull frozen-thawed semen. AB - The objective of this study was to investigate the quality of frozen-thawed semen from different bull breeds. Commercial frozen-thawed bull semen samples (26 per breed, 130 totally) of five breeds (Holstein [Eta], Brown Swiss [BS], Limousin [L], Belgian Blue [BB], Blonde d' Aquitaine [BA]) were used. After thawing, each semen sample was subjected to thermal resistance test (TR) for 0.5 and 1 hr at 38 degrees C and hypo-osmotic swelling test (HOST) for 1 hr at 150 mOsm at 37 degrees C. Additionally, all samples were evaluated at times 0 hr (thawing), 0.5 hr (TR), 1 hr (TR) for kinetics by CASA [progressive, immotile, rapid, medium, slow moving spermatozoa, curvilinear velocity (VCL), average path velocity (VAP), straight line velocity (VSL), linearity (LIN), straightness (STR), beat cross frequency (BCF), amplitude of lateral head displacement (ALH), wobble (WOB)]. Moreover, directly after thawing, all semen samples were evaluated for morphometry, morphology, viability and DNA fragmentation. Statistical analysis was conducted using a mixed model for repeated measures. The results showed (a) higher VCL after thawing in H, L breeds compared to BB and BA, (b) higher VAP after thawing in L compared to BB, BA, (c) higher values of progressive spermatozoa after TR in H, BS compared to BB, BA, (d) higher values of rapid spermatozoa after thawing and 0.5 hr of TR in H, BS, L compared to BB, BA, (e) lower viability in BA after thawing compared to H, BS, BB, (f) lower morphological abnormalities in H compared to L, BB, (g) higher head length in Eta compared to BB. No significant differences were observed in the results from HOST and DNA fragmentation between breeds. In conclusion, quality characteristics of frozen-thawed bull semen are dependent on the breed. Frozen semen from BB and BA breeds should be handled more carefully after thawing, as it is more sensitive to stress. PMID- 27667129 TI - Promoting similarity of model sparsity structures in integrative analysis of cancer genetic data. AB - In profiling studies, the analysis of a single dataset often leads to unsatisfactory results because of the small sample size. Multi-dataset analysis utilizes information of multiple independent datasets and outperforms single dataset analysis. Among the available multi-dataset analysis methods, integrative analysis methods aggregate and analyze raw data and outperform meta-analysis methods, which analyze multiple datasets separately and then pool summary statistics. In this study, we conduct integrative analysis and marker selection under the heterogeneity structure, which allows different datasets to have overlapping but not necessarily identical sets of markers. Under certain scenarios, it is reasonable to expect some similarity of identified marker sets - or equivalently, similarity of model sparsity structures - across multiple datasets. However, the existing methods do not have a mechanism to explicitly promote such similarity. To tackle this problem, we develop a sparse boosting method. This method uses a BIC/HDBIC criterion to select weak learners in boosting and encourages sparsity. A new penalty is introduced to promote the similarity of model sparsity structures across datasets. The proposed method has a intuitive formulation and is broadly applicable and computationally affordable. In numerical studies, we analyze right censored survival data under the accelerated failure time model. Simulation shows that the proposed method outperforms alternative boosting and penalization methods with more accurate marker identification. The analysis of three breast cancer prognosis datasets shows that the proposed method can identify marker sets with increased similarity across datasets and improved prediction performance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27667131 TI - TRT, a Vertebrate and Protozoan Tc1-Like Transposon: Current Activity and Horizontal Transfer. AB - We report a Danio rerio transposon named DrTRT, for D. rerio Transposon Related to Tc1 The complete sequence of the DrTRT transposon is 1,563 base pairs (bp) in length, and its transposase putatively encodes a 338-amino acid protein that harbors a DD37E motif in its catalytic domain. We present evidence based on searches of publicly available genomes that TRT elements commonly occur in vertebrates and protozoa. Phylogenetic and functional domain comparisons confirm that TRT constitutes a new subfamily within the Tc1 family. Hallmark features of having no premature termination codons within the transposase, the presence of all expected functional domains, and its occurrence in the bony fish transcriptome suggest that TRT might have current or recent activity in these species. Further analysis showed that the activity of TRT elements in these species might have arisen about between 4 and 19 Ma. Interestingly, our results also implied that the widespread distribution of TRT among fishes, frog, and snakes is the result of multiple independent HT events, probably from bony fishes to snakes or frog. Finally, the mechanisms underlying horizontal transfer of TRT elements are discussed. PMID- 27667132 TI - Assessing the composition of microbial communities in textile wastewater treatment plants in comparison with municipal wastewater treatment plants. AB - It is assumed that microbial communities involved in the biological treatment of different wastewaters having a different chemical composition harbor different microbial populations which are specifically adapted to the environmental stresses encountered in these systems. Yet, little is known about the composition of these microbial communities. Therefore, the aim of this study was to assess the microbial community composition over two seasons (winter and summer) in activated sludge from well-operating textile wastewater treatment plants (WWTPs) in comparison with municipal WWTPs, and to explain observed differences by environmental variables. 454-pyrosequencing generated 160 archaeal and 1645 bacterial species-level Operational Taxonomic Units (OTUs), with lower observed richness in activated sludge from textile WWTPs compared to municipal WWTPs. The bacterial phyla Planctomycetes, Chloroflexi, Chlorobi, and Acidobacteria were more abundant in activated sludge samples from textile WWTPs, together with archaeal members of Thaumarchaeota. Nonmetric multidimensional scaling analysis of the microbial communities showed that microbial communities from textile and municipal WWTPs were significantly different, with a seasonal effect on archaea. Nitrifying and denitrifying bacteria as well as phosphate-accumulation bacteria were more abundant in municipal WWTPs, while sulfate-reducing bacteria were almost only detected in textile WWTPs. Additionally, microbial communities from textile WWTPs were more dissimilar than those of municipal WWTPs, possibly due to a wider diversity in environmental stresses to which microbial communities in textile WWTPs are subjected to. High salinity, high organic loads, and a higher water temperature were important potential variables driving the microbial community composition in textile WWTPs. This study provides a general view on the composition of microbial communities in activated sludge of textile WWTPs, and may provide novel insights for identifying key players performing important functions in the purification of textile wastewaters. PMID- 27667134 TI - Correction to "Encapsulating Mobile Proton Carriers into Structural Defects in Coordination Polymer Crystals: High Anhydrous Proton Conduction and Fuel Cell Application". PMID- 27667133 TI - Hepatitis E virus RNA in Australian blood donations. AB - BACKGROUND: Hepatitis E virus (HEV) poses a risk to transfusion safety. In Australia, locally acquired HEV is rare and cases are mainly reported in travelers returning from countries endemic for HEV. The risk posed by HEV to transfusion safety in Australia is unknown; therefore, we aimed to measure the rate of current HEV infection in Australian blood donations. STUDY DESIGN AND METHODS: A total of 14,799 blood donations were tested for HEV RNA by transcription-mediated amplification, with confirmatory testing by reverse transcription-polymerase chain reaction. Viral load quantification and phylogenetic analysis was performed on HEV RNA-positive samples. RESULTS: One (0.0068%; 95% confidence interval [CI], 0.0002%-0.0376%) sample was confirmed positive for HEV RNA, resulting in a risk of collecting a HEV-viremic donation of 1 in 14,799 (95% CI, 1 in 584,530 to 1 in 2,657). The viral load in this sample was approximately 15,000 IU/mL, and it was determined to be Genotype 3. DISCUSSION: Our finding of 1 in 14,799 Australian donations positive for HEV RNA is lower than that from many other developed countries; this is consistent with the relatively low seroprevalence in Australia. As this HEV RNA-positive sample was Genotype 3, it seems likely that this infection was acquired through zoonotic transmission, either within Australia or overseas in a developed nation. HEV has the potential to pose a risk to transfusion safety in Australia; however, additional, larger studies are required to quantify the magnitude of this risk. PMID- 27667135 TI - Prevention of bronchiolitis obliterans-the realization of a hope? PMID- 27667136 TI - The phylogeny and life cycle of two species of Profilicollis (Acanthocephala: Polymorphidae) in marine hosts off the Pacific coast of Chile. AB - Resolving complex life cycles of parasites is a major goal of parasitological research. The aim of this study was to analyse the life cycle of two species of the genus Profilicollis, the taxonomy of which is still unstable and life cycles unclear. We extracted individuals of Profilicollis from two species of crustaceans (intermediate hosts) and four species of seagulls (definitive hosts) from sandy-shore and estuarine habitats along the south-east Pacific coast of Chile. Mitochondrial DNA analyses showed that two species of Profilicollis infected intermediate hosts from segregated habitats: while P. altmani larvae infected exclusively molecrabs of the genus Emerita from fully marine habitats, P. antarcticus larvae infected the crab Hemigrapsus crenulatus from estuarine habitats. Moreover, P. altmani completed its life cycle in four seagulls, Chroicocephalus maculipennis, Leucopheus pipixcan, Larus modestus and L. dominicanus, while P. antarcticus, on the other hand, completed its life cycle in the kelp gull L. dominicanus. Accordingly, our results show that two congeneric parasites use different and spatially segregated species as intermediate hosts, and both are capable of infecting one species of definitive hosts. As such, our analyses allow us to shed light on a complex interaction network. PMID- 27667137 TI - Nanoparticle Based Delivery of Protease Inhibitors to Cancer Cells. AB - Proteases are involved in a variety of processes associated with tumor development and progression. Because of their integral role in extracellular matrix and basal lamina degradation they play important roles in cancer cell migration, invasion, angiogenesis and metastasis. They are also involved in cancer cell signaling, the epithelial-mesenchymal transition, the antitumor immune response, cell de-differentiation and cancer stem cell remodeling. Their involvement in pro-tumorigenic processes makes them interesting targets for anticancer therapy. The most promising are matrix metalloproteases, cysteine cathepsins, the urokinase-type plasminogen activator system and proteasome; these constitute the focus of this review. Several inhibitors have been developed for reducing their activities that are in different phases of development, with some already in clinical use. However, systemic delivery of protease inhibitors can result in undesired reduction of proteolytic activity in normal tissues, leading to adverse effects and limited therapeutic efficacy. This caveat can be circumvented by nanoparticle delivery systems that direct protease inhibitors specifically to cancer cells. In this article we review the current state of nanoparticle delivery systems for delivering protease inhibitors to cancer cells. PMID- 27667139 TI - Successful multitarget therapy using prednisolone, mizoribine and tacrolimus for Henoch-Schonlein purpura nephritis in children. PMID- 27667138 TI - "How I manage" IgG4-Related Disease. AB - IgG4-related disease (IgG4-RD) is an immune-mediated disease driven by interactions on several levels between cells of the B and T lineages. A key driver of IgG4-RD is believed to be a novel CD4+ cytotoxic T lymphocyte that bears SLAM-F7 on its surface. This cell is presumed to be sustained by continuous antigen presentation by cells of the B cell lineage, particularly plasmablasts. Because IgG4-RD has been recognized for fewer than 15 years as a unified diagnostic entity, no controlled clinical trials or few prospective studies of any sort have been performed. Although progress in understanding disease pathophysiology will likely lead in due course to disease-specific therapies undoubtedly with implications for other immune-mediated diseases-at this juncture, the management of IgG4-RD remains more an art than a science, driven largely by the published clinical experience of only a few centers of expertise. We identify here six common management dilemmas in IgG4-RD and describe our typical approach to the management of each one. PMID- 27667140 TI - 'Everyone here wants everyone else to get better': The role of social identity in eating disorder recovery. AB - Retention of a positively valued illness identity contributes to poor outcomes for individuals with eating disorders (EDs). Consequently, dis-identification from the illness identity and the adoption of a recovery identity are vital for successful recovery. While social identity processes have been shown to influence ED maintenance, their role in recovery is rarely considered. This study explores how a sense of shared identity helps individuals with EDs manage their condition and promotes recovery. Transcripts from 18 online support sessions involving 75 participants were thematically analysed. Our findings suggest that the illness identity initially operates as a social identity that forms the basis for connections with similar others. For those wishing to recover, identity-based support is then perceived to be more effective than that found outside the group. Online interactions also facilitate construction of a new shared recovery identity which promotes a shift from the illness identity as a primary source of definition and endorses group norms of illness disclosure and treatment engagement. While in the clinical literature, ED identity is seen as problematic and interventions are targeted at challenging an individual's self-concept, we suggest that interventions could instead harness identity resources to support a transition to a recovery identity. PMID- 27667141 TI - Discovery of a Mosaic-Like Biosynthetic Assembly Line with a Decarboxylative Off Loading Mechanism through a Combination of Genome Mining and Imaging. AB - The biosynthetic gene cluster for the antiplasmodial natural product siphonazole was identified by using a combination of genome mining, imaging, and expression studies in the natural producer Herpetosiphon sp. B060. The siphonazole backbone is assembled from an unusual starter unit from the shikimate pathway that is extended by the action of polyketide synthases and non-ribosomal peptide synthetases with unusual domain structures, including several split modules and a large number of duplicated domains and domains predicted to be inactive. Product release proceeds through decarboxylation and dehydration independent of the thioesterase SphJ and yields the diene terminus of siphonazole. High variation in terms of codon-usage within the gene cluster, together with the dislocated domain organization, suggest a recent emergence in evolutionary terms. PMID- 27667142 TI - A neonate with a unique non-Down syndrome transient proliferative megakaryoblastic disease. AB - Transient myeloproliferative disorder (TMD) is a leukemia type that occurs typically in newborns. In Down syndrome, TMD is referred to as transient abnormal myelopoiesis (TAM).32 Recently, transientness has also been reported in acute myeloid leukemia patients with germline trisomy 21 mosaicism, and even in cases with somatic trisomy 21, with or without GATA1 mutations. TMD cases without trisomy 21 are rare, and recurrent genetic aberrations that aid in clinical decision-making are scarcely described. We describe here a TMD patient without trisomy 21 or GATA1 mutation in whom single-nucleotide polymorphism analysis of leukemic blasts revealed a novel combined submicroscopic deletion (5q31.1-5q31.3 and 8q23.2q24). PMID- 27667143 TI - Complete Genome Sequencing and Comparative Genomic Analysis of the Thermotolerant Acetic Acid Bacterium, Acetobacter pasteurianus SKU1108, Provide a New Insight into Thermotolerance. AB - Acetobacter pasteurianus SKU1108 is a typical thermotolerant acetic acid bacterium. In this study, the complete genome sequence of the SKU1108 strain was elucidated, and information on genomic modifications due to the thermal adaptation of SKU1108 was updated. In order to obtain a clearer understanding of the genetic background responsible for thermotolerance, the SKU1108 genome was compared with those of two closely related complete genome strains, thermotolerant A. pasteurianus 386B and mesophilic A. pasteurianus NBRC 3283. All 24 "thermotolerant genes" required for growth at higher temperatures in the thermotolerant Acetobacter tropicalis SKU1100 strain were conserved in all three strains. However, these thermotolerant genes accumulated amino acid mutations. Some biased mutations, particularly those that occurred in xanthine dehydrogenase XdhA, may be related to thermotolerance. By aligning whole genome sequences, we identified ten SKU1108 strain-specific regions, three of which were conserved in the genomes of the two thermotolerant A. pasteurianus strains. One of the regions contained a unique paralog of the thermotolerant gene xdhA, which may also be responsible for conferring thermotolerance. Thus, comparative genomics of complete genome sequences may provide novel insights into the phenotypes of these thermotolerant strains. PMID- 27667144 TI - [Lixisenatide in patients with type 2 diabetes and obesity: Beyond glycaemic control]. AB - AIM: To evaluate tolerance to lixisenatide and its effects on weight and metabolic control in type2 diabetes and obese patients. DESIGN: Prospective study. SETTING: Endocrinology clinics in Almeria, Granada and Malaga. PARTICIPANTS: Patients with type2 diabetes and obesity. INTERVENTIONS: Response and tolerance to lixisenatide treatment. MAIN MEASUREMENTS: Clinical and analytical data of the subjects were evaluated at baseline and after treatment. RESULTS: The study included 104 patients (51% women) with type2 diabetes and obesity (Almeria 18.3%; Granada 40.4%; Malaga 41.3%). The mean age was 58.4+/ 10.5years, and the mean duration of diabetes was 11.2+/-6.7years. The patients were re-evaluated at 3.8+/-1.6months after treatment with lixisenatide. Significant improvements were found in weight (P<.001), body mass index (P<.001), waist circumference (P=.002), systolic blood pressure (P<.001), diastolic blood pressure (P=.001), fasting glucose (P<.001), HbA1c (P=.022), Total cholesterol (P<.001), LDL-cholesterol (P=.046), triglycerides (P=.020), hypertension drugs (P<.001), and lipids drugs (P<.001). No changes were observed in levels of amylase related to lixisenatide treatment, and 7.9% of patients did not tolerate it. CONCLUSIONS: Lixisenatide achieved significant improvements in anthropometric parameters, glycaemic control (fasting glucose and HbA1c), blood pressure and lipids. It was safe and well tolerated in most patients. In addition, there was a significant increase in the use of antihypertensive and lipid-lowering therapy. PMID- 27667145 TI - [Social isolation and loneliness: What can we do as Primary Care teams?] AB - Loneliness and social isolation are emerging health conditions in the elderly population, in particular widows, high frequency users of health services and those with chronic problems and depression. Loneliness is the subjective feeling of having less affection and closeness than that desired in the intimate or relational field. Social isolation is an objective situation of having minimal contact with other people. Its contribution to increased morbidity and mortality is comparable to other well known risk factors that we deal with daily as Primary Care teams. Strategies to identify these problems in our patients and to perform scientific evidence based studies at individual and community level in cooperation with other community resources and interventions are discussed. The Primary Care team must promote the autonomy of these patients, facilitating their sociability, and act on their social maladaptive thoughts that hinder their social integration. PMID- 27667146 TI - [Do we care the nephrotoxicity consequences of prescribing NSAID'S? Acute renal failure in 23 year old male]. PMID- 27667147 TI - [Efficacy of anti-inflammatory non-steroidal drugs in the treatment of knee and hip pain]. PMID- 27667148 TI - The JAK/STAT3 signalling pathway regulated angiogenesis in an endothelial cell/adipose-derived stromal cell co-culture, 3D gel model. AB - OBJECTIVES: The aim of the study was to investigate the role of the JAK/STAT3 signalling pathway in angiogenesis. MATERIALS AND METHODS: The model established in vitro, involved a 3D collagen gel being implanted with endothelial cells (ECs) from red fluorescent protein-labelled mice, and adipose-derived stromal cells (ASCs) from green fluorescent protein-labelled mice. Phenomena of angiogenesis, after treatment by the inhibitor and the activator of JAK/STAT3 pathway respectively, were observed using confocal laser scanning microscopy. Transwell co-culture of ECs and ASCs was used to elucidate mechanisms. RESULTS: Stattic, inhibitor of JAK/STAT3 pathway, attenuated angiogenesis in the model. In contrast, angiogenesis was promoted after treatment of Olanzapine, an activator. We found that protein levels of VEGFA and cyclin D1 were regulated by the JAK/STAT3 pathway, and flow cytometry further confirmed variations in cell cycle parameters of ECs and ASCs. Genes VEGFA/B, VEGFR2, MMP-2, MMP-9, IGF-1 and b-FGF were down-regulated by Stattic in ECs, while Olanzapine significantly up regulated mRNA levels of these genes. As for ASCs, genes VEGFA, MMP-2, MMP-9, IGF 1 and b-FGF were modulated by the JAK/STAT3 pathway. CONCLUSIONS: Angiogenesis in the 3D collagen gel was regulated by the JAK/STAT3 pathway which involved changes in vessel length, vessel diameter and sprout number. The underlying mechanism was that the JAK/STAT3 signalling pathway regulated angiogenesis by modulation of numbers of angiogenesis-related growth factors and by direct regulation of cell cycle. PMID- 27667149 TI - Patients with diabetes differ in atherosclerotic plaque characteristics and have worse clinical outcome after iliofemoral endarterectomy compared with patients without diabetes. AB - OBJECTIVE: Diabetes mellitus (DM) is associated with peripheral arterial disease (PAD) and leads to worse clinical outcome compared with patients without DM. The objective of this study was to determine the impact of DM on iliofemoral artery plaque characteristics and to examine secondary clinical outcomes in patients with DM and PAD undergoing surgical revascularization. METHODS: We analyzed 198 patients with and 453 patients without DM from the Athero-Express biobank, a prospective ongoing biobank study, who underwent endarterectomy of the femoral or iliac artery between 2002 and 2013. Seven histologic plaque characteristics (calcification, collagen, lipid core, intraplaque hemorrhage, macrophages, microvessels, and smooth muscle cells) and secondary clinical outcome were compared. Composite outcome consisted of any of the following secondary manifestations of cardiovascular disease: stroke, myocardial infarction, cardiovascular death, or peripheral intervention. In addition, target vessel revascularization (TVR) was examined. The follow-up period was standardized at 3 years after the procedure. RESULTS: Patients with DM were more likely to have calcified plaques compared with patients without DM (odds ratio, 2.11; 95% confidence interval, 1.43-3.12; P < .01). No other plaque characteristic differed significantly between the two groups. In total, 112 (57.1%) patients with DM and 198 (45.1%) patients without DM reached a composite end point during follow-up, of whom 21 (10.7%) and 27 (6.2%) died of cardiovascular causes, respectively. DM was an independent predictor of composite cardiovascular events (hazard ratio, 1.36; 95% confidence interval, 1.020-1.801; P = .01) during follow-up. No difference in the incidence of TVR was observed between patients with and without DM (31.5% and 30%, respectively; difference in survival time, P = .86) or in longer duration of DM with composite event-free survival (difference in survival time, P = .57). CONCLUSIONS: Patients with DM who undergo surgical revascularization for PAD with the use of thromboendarterectomy or remote endarterectomy have a more calcified atherosclerotic plaque and an increased incidence in composite cardiovascular events but no increase in TVR. PMID- 27667150 TI - The role of the kallikrein-kinin system, matrix metalloproteinases, and tissue inhibitors of metalloproteinases in the early restenosis of covered stents in the femoropopliteal arterial segment. AB - OBJECTIVE: The purpose of this study was to investigate the roles of the kallikrein-kinin system and matrix metalloproteinases (MMPs) in the development of arterial restenosis attributable to intimal hyperplasia in the femoropopliteal arteries. METHODS: This report describes a single-center prospective study of 27 patients with peripheral artery disease who required percutaneous transluminal angioplasty and stenting of the femoropopliteal segment using covered stent grafts. The blood concentrations of total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein was evaluated by the colorimetric method. Tissue kallikrein was evaluated by the spectrophotometric method. The activity of kininase II was measured by fluorometric analysis. Quantification of MMPs was performed by zymography, and tissue inhibitors of metalloproteinases were measured by enzyme-linked immunosorbent assay. RESULTS: Four (15%) of the treated patients developed restenosis at the 6-month follow-up evaluation. These patients had significantly lower levels of high-molecular weight kininogens (24 hours; P < .05) and low-molecular-weight kininogens (before, P < .05; 24 hours, P < .01; 6 months, P < .05) and lower levels of tissue inhibitor of metalloproteinases-2 (6 months; P < .05) than the patients without restenosis. The activity levels of plasma and tissue kallikrein, kininase II, and MMPs did not differ significantly between the patients with and without restenosis. CONCLUSIONS: This study demonstrates an involvement of the kallikrein kinin system in in-stent restenosis, although we could not confirm the participation of metalloproteinases in the restenosis process. PMID- 27667151 TI - Elevated serum phosphate levels are associated with decreased amputation-free survival after interventions for critical limb ischemia. AB - OBJECTIVE: Elevated serum phosphate levels have been associated with increased risks of cardiovascular events and death in several patient populations. The effects of serum phosphate on outcomes in patients with critical limb ischemia (CLI) have not been evaluated. In this study, we assessed the effect of abnormal phosphate levels on mortality and major limb events after surgical intervention for CLI. METHODS: A retrospective review was undertaken to identify all patients at a single institution who underwent a first-time open or endovascular intervention for CLI between 2005 and 2014. Patients without recorded postoperative phosphate levels were excluded. Postoperative phosphate levels <=30 days of the initial operation were recorded, and the mean was calculated. Patients were stratified according to mean phosphate levels (low: <2.5 mg/dL, normal: 2.5-4.5 mg/dL, and high: >4.5 mg/dL). Patient demographics, comorbidities, and operative details were compared in univariate analysis. Multivariable regression and Cox proportional hazard modeling were used to account for patient demographics and comorbid conditions. RESULTS: We identified 941 patients, including 42 (5%) with low phosphate, 768 (82%) with normal phosphate, and 131 (14%) with high phosphate. Patients with elevated phosphate were younger and had higher rates of congestive heart failure, diabetes, and dialysis dependence. Bypass was more common among patients with normal phosphate compared with high or low phosphate levels. There was no difference in the Wound, ischemia, and Foot infection (WiFi) classification or TransAtlantic Inter-Society Consensus classification among the cohorts. There were significant differences in 1-year mortality (low: 19%, normal: 17%, high: 33%; P < .01) and 3-year mortality (low: 38%, normal: 34%, high: 56%; P < .01) between phosphate cohorts. Major amputation (low: 12%, normal: 12%, high: 15%) and restenosis (low: 21%, normal: 24%, high: 28%) tended toward worse outcomes among patients with elevated phosphate levels but did not reach statistical significance. After adjustment for baseline characteristics, mortality was higher (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.2) and amputation-free survival was lower (HR, 1.5; 95% CI, 1.2-1.9) among patients with elevated compared with normal phosphate levels. A subgroup analysis was then performed to assess dialysis and nondialysis patients separately. Patients with elevated serum phosphate levels maintained a significantly higher risk of mortality in each group (dialysis: HR, 1.8; 95% CI, 1.2-2.6; nondialysis: HR, 1.5; 95% CI, 1.04-2.10). CONCLUSIONS: Elevated phosphate levels are associated with increased mortality and decreased amputation free survival after interventions for CLI. Future studies evaluating the effects of phosphate reduction in patients with CLI are warranted. PMID- 27667152 TI - Long non-coding RNAs, ASAP1-IT1, FAM215A, and LINC00472, in epithelial ovarian cancer. AB - OBJECTIVE: Long non-coding RNAs (lncRNAs) are a class of non-protein coding transcripts that has gained significant attention lately due to their important biological actions and potential involvement in cancer. Ovarian cancer is a devastating disease with poor prognosis, and our understanding of lncRNA's involvement in the malignancy is limited. To further our knowledge, we measured the expression of three lncRNAs, ASAP1-IT1, FAM215A, and LINC00472, in tumor samples, and analyzed their associations with disease characteristics and patient survival. METHODS: Two hundred sixty-six patients diagnosed with primary epithelial ovarian cancers were recruited for the study. Fresh-frozen tumor samples were obtained from the patients at tumor resection and analyzed by RT qPCR for expression of ASAP1-IT1, FAM215A, and LINC00472. Associations of lncRNA expression with patient survival were determined using Cox proportional hazards regression models. RESULTS: We observed high expression of ASAP1-IT1, FAM215A and LINC00472 more frequently in low grade tumors and early stage disease compared to high grade tumors and late stage disease, respectively. High expression of ASAP1 IT1 and FAM215A were associated with favorable overall survival, and the survival association with ASAP1-IT1 was independent of tumor grade and disease stage. Analyses of online data also demonstrated similar survival associations with ASAP1-IT1 and FAM215A, suggesting that these lncRNAs may be involved in ovarian cancer progression. CONCLUSIONS: LncRNAs may play appreciable roles in ovarian cancer and more research is needed to elucidate their biological mechanisms and clinical implications in tumor characterization as well as disease prognosis and treatment. PMID- 27667153 TI - Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid dependent effects in human alloreactive CD4+ T-cells. AB - Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and by degrading L-tryptophan along the kynurenine pathway suppresses CD4+ T-cell proliferation, induces apoptosis and promotes differentiation towards a regulatory as opposed to an effector phenotype. Recent findings revealed that the above effects may be mediated through alterations in T-cell metabolism. In this study, the effect of IDO on fatty acid beta-oxidation in CD4+ T-cells was evaluated in human mixed lymphocyte reactions (MLRs) using the IDO inhibitor, 1 DL-methyl-tryptophan. Protein analysis of CD4+ T-cells isolated from the MLR showed that L-tryptophan degradation acts by activating the general control non derepressible 2 kinase and aryl-hydrocarbon receptor in T-cells. In the absence of IDO inhibition, fatty acid oxidation increased along with increased activity of carnitine palmitoyltransferase I (CPT1), the latter due to the increased expression of CPT1 isoenzymes and alterations in acetyl-CoA carboxylase 2, the enzyme that controls CPT1 activity. Increased fatty acid oxidation due to the action of IDO was accompanied by an increased expression of forkhead box P3 (FoxP3) and a decreased expression of related orphan receptor gammat (RORgammat), the signature transcription factors of regulatory T-cells and T helper 17 cells, respectively. However, in MLR and in the presence of fatty acid in the culture medium, IDO did not inhibit proliferation. Additionally, fatty acid protected the CD4+ T-cells against apoptosis. Thus, IDO, by degrading L-tryptophan, enhances CPT1 activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells. PMID- 27667154 TI - Seasonal variations of plasma testosterone among colour-morph common wall lizards (Podarcis muralis). AB - Sexual steroids influence reproductive behaviours and promote secondary sexual traits. In male lizards, increasing levels of testosterone (T) bolster conspicuous colouration, stimulate territoriality, and trigger antagonistic interactions among rivals. Moreover, in colour polymorphic species, reproductive strategy, aggressiveness and T levels can differ between morphs. Therefore, T level is considered as an important mechanism that regulates the expression of colour polymorphism and sexual behaviours of males. But in the polymorphic territorial wall lizard (Podarcis muralis), a lack of relationship between morphs and aggressiveness challenges the notion that T plays such a role. To examine this issue, we compared adult T levels among three colour morphs (white, yellow and red) through repeated sampling during the mating season. High T levels were observed at the onset of the mating season followed by a significant decrease, a pattern documented in other lizard species. Mean T levels did not differ among morphs. However, yellow males maintained significantly higher T levels over time and displayed a stronger subsequent decline. Overall, in this species, seasonal T patterns differ among morphs, not mean values. Previous studies revealed that T suppresses the immune response; suggesting that a strong initial investment promoted by high T levels may trade-off against immunity (maintenance). Further experimental investigations are required to clarify the relationship between T and reproductive effort in polymorphic species that exhibit complex temporal pattern of T levels. PMID- 27667155 TI - Gonadotropin-inhibitory hormone (GnIH) in the amphibian brain and its relationship with the gonadotropin releasing hormone (GnRH) system: An overview. AB - It is well known that the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role as a primary factor regulating gonadotropin secretion in reproductive processes in vertebrates. The discovery of the presence of a gonadotropin-inhibitory hormone (GnIH) in the brains of birds has further contributed to our understanding of the reproduction control by the brain. GnIH plays a key role in inhibition of reproduction and acts on the pituitary gland and GnRH neurons via a novel G protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and release, thus inhibiting gonadal development and maintenance. The GnRH and GnIH neuronal peptidergic systems are well reported in mammals and birds, but limited information is available regarding their presence and localization in the brains of other vertebrate species, such as reptiles, amphibians and fishes. The aim of this review is to compile and update information on the localization of GnRH and GnIH neuronal systems, with a particular focus on amphibians, summarizing the neuroanatomical distribution of GnIH and GnRH and emphasizing the discovery of GnIH based on RFamide peptides and GnIH orthologous peptides found in other vertebrates and their functional significance. PMID- 27667156 TI - Metastatic Tumor Burden Does Not Predict Overall Survival Following Cytoreductive Nephrectomy for Renal Cell Carcinoma: a Novel 3-Dimensional Volumetric Analysis. AB - OBJECTIVE: To compare 1-dimensional (1D) and 3-dimensional (3D) volume measurements and determine whether primary tumor (PT) burden is predictive of overall survival (OS) following cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Records and imaging studies of patients with mRCC treated with CN from 2006 to 2015 were included, with tumor volumes measured by a faculty radiologist blinded to clinical outcomes using Advantage Workstation Volume Share (Ver 4.6, GE, Waukesha, WI). RESULTS: Complete PT and metastatic tumor volumes were measured for 67 patients. For 15 (22.3%) patients, 1D volume was within +/-10% of the measured 3D volume. In 40 (59.7%) patients, the 1D calculated PT volume was >10% of the actual 3D volume. Fractional percentage of tumor volume (FPTV) removed during CN was calculated using the formula PT volume/(PT + met volume). FPTV was not associated with OS when analyzed as a continuous variable. Patients were divided into 2 groups based on previously published cut point of 90% FPTV. No differences between cohorts in age, gender, grade, subtype, number of metastatic sites, performance status, Memorial Sloan Kettering Cancer Center risk group, or International Metastatic Renal Cell Carcinoma Database Consortium risk group were identified. OS was not different between cohorts (P = .38). CONCLUSION: 1D measurements of PT diameter frequently overestimate mRCC PT volume. In patients with mRCC selected for CN, the ratio of primary to metastatic tumor does not predict OS. PMID- 27667157 TI - Racial/Ethnic Disparity in Treatment for Prostate Cancer: Does Cancer Severity Matter? AB - OBJECTIVE: To determine if there are variations in the receipt of treatment based on race and disease severity. Treatment variations in men with prostate cancer (PCa) among the various racial groups in the United States exist, which may be a source of potential disparity in outcome. METHODS: Utilizing Surveillance, Epidemiology and End Results 17, we identified 327,636 men diagnosed with PCa from 2004 to 2011. Logistic regression analysis was performed to determine the association of receiving definitive treatment and race in the context of disease severity. RESULTS: African American (AA) and Hispanic men were less likely to receive treatment compared to White men (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.71, 0.75, and OR 0.95, 95% CI 0.92, 0.98, respectively). AA men had significantly lower OR of receiving definitive treatment within each D'Amico risk classification compared to White men, with decreasing odds of treatment for each increase in risk category (low-risk OR 0.81, 95% CI 0.78, 0.85; intermediate risk OR 0.74, 95% CI 0.71, 0.77; and high-risk OR 0.62, 95% CI 0.58, 0.66). Hispanic men with intermediate-risk (OR 0.89, 95% CI 0.84, 0.94) or high-risk (OR 0.79, 95% CI 0.72, 0.85) disease had lower odds of receiving treatment compared to White men. Asian men had similar or greater odds of receiving treatment compared to White men within any Gleason or D'Amico classification. CONCLUSION: There is a significant disparity in the receipt of treatment for PCa among AA and Hispanic men compared to White men. The variations in receipt of treatment reveal an area of opportunity to develop risk-stratified approaches to treatment regardless of ethnic identity, which may address the poorer PCa-related outcomes in these populations. PMID- 27667158 TI - Can We Use Single-step Dilation as a Safe Alternative Dilation Method in Percutaneous Nephrolithotomy? AB - OBJECTIVE: To examine the outcomes of the patients who underwent percutaneous nephrolithotomy with single-step dilatation technique in our clinic. MATERIALS AND METHODS: A total of 932 patients who underwent percutaneous nephrolithotomy by using single-step dilation technique in the period between 2008 and 2015 in our clinic were included in the study. Data of the patients were analyzed, such as age, sex, stone burden, operative time, fluoroscopy time, operation success, and perioperative and postoperative complications. RESULTS: An analysis of the data of 932 patients revealed similar operation success and complication rates as in the literature. Mean age of the patients included in the study was 48.9 years. Mean operative time was 66.6 minutes and mean fluoroscopy time was 139 seconds. Postoperative residual stone was detected in 17.1% of the patients. Postoperative fever was observed in 29 patients (3.1%), and sepsis developed in 11 (1.1%) of them. Additional postoperative procedures were required in 29 patients (3.1%). No patient was lost due to complications. Our data were compatible with the literature. CONCLUSION: Single-step dilation technique can be used as an effective and safe alternative dilation method in adult patients. PMID- 27667159 TI - Association between a combination of single nucleotide polymorphisms and large vessel cerebral vasculopathy in African children with sickle cell disease. PMID- 27667161 TI - Next-generation sequencing of hereditary hemochromatosis-related genes: Novel likely pathogenic variants found in the Portuguese population. AB - Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1G>C)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c. 25G>A). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism related disorders. PMID- 27667162 TI - Inflammation-induced up-regulation of hepcidin and down-regulation of ferroportin transcription are dependent on macrophage polarization. AB - Iron is essential in all organisms. In mammals systemic iron homeostasis relies on hepcidin, a peptide hormone with defensin properties, and its target, the cell iron exporter ferroportin. Hepcidin and ferroportin transcription are both upregulated by high iron levels, but are inversely regulated upon inflammation, leading to hypoferremia. Thus, host iron genes regulation may affect the innate immune responses against infectious microorganisms. Since macrophages, which are crucial innate immune cells, express both hepcidin and ferroportin, we explored in these cells their transcriptional regulation upon inflammation which is not completely understood. Macrophages represent an heterogenous population of immune cells resulting from cytokine and pathogen sensing, indeed macrophages polarized especially into pro-inflammatory M1 and regulatory/anti-inflammatory M2 phenotypes. We found that hepcidin mRNA upregulation depends on M1 polarization and ferroportin mRNA downregulation depends on M2 subtype polarization. All TLR agonists, except TLR2 agonist, polarize to pro-inflammatory macrophages and upregulate hepcidin mRNA expression. Cell pretreatment with IFNgamma or inhibitor of PI3K, p38-MAPK and NF-kappaB pathway involved in M1 polarization prior TLR4 activation, enhanced hepcidin upregulation. Conversely, ferroportin mRNA downregulation upon inflammation was strongly increased by macrophage polarization through TLR2- and 4-PI3K-dependent pathways, or through IL-1beta and TNFalpha priming prior to LPS activation. PMID- 27667160 TI - Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. AB - Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are heterogeneous red blood cell (RBC) membrane disorders that result from mutations in the genes encoding alpha-spectrin (SPTA1), beta-spectrin (SPTB), or protein 4.1R (EPB41). The resulting defects alter the horizontal cytoskeletal associations and affect RBC membrane stability and deformability causing shortened RBC survival. The clinical diagnosis of HE and HPP relies on identifying characteristic RBC morphology on peripheral blood smear and specific membrane biomechanical properties using osmotic gradient ektacytometry. However, this phenotypic diagnosis may not be readily available in patients requiring frequent transfusions, and does not predict disease course or severity. Using Next-Generation sequencing, we identified the causative genetic mutations in fifteen patients with clinically suspected HE or HPP and correlated the identified mutations with the clinical phenotype and ektacytometry profile. In addition to identifying three novel mutations, gene sequencing confirmed and, when the RBC morphology was not evaluable, identified the diagnosis. Moreover, genotypic differences justified the phenotypic differences within families with HE/HPP. PMID- 27667163 TI - Differences in frequency and regulation of T follicular helper cells between newly diagnosed and chronic pediatric immune thrombocytopenia. AB - OBJECTIVE: This study aims to investigate the role of T follicular helper (TFH) cells in the immunopathogenesis of pediatric immune thrombocytopenia (ITP), as well as differences in TFH expansion and its regulation between newly diagnosed ITP (nITP) and chronic pediatric ITP (cITP). METHODS: Eighty-five children with ITP and 20 age-matched healthy controls were enrolled into this study. TFH cell frequencies and TFH cell-associated regulatory factors before and after treatment were analyzed by flow cytometry, RT-PCR and ELISA. RESULTS: The percentages of TFH cells were significantly elevated in both nITP and cITP compared with controls. RT-PCR revealed significant differences in Bcl-6, c-Maf, Blimp-1, ICOSL, TACI and BAFFR mRNA expression in CD4(+) T or CD19(+) B cells between patients and controls, and further between nITP and cITP, before and after treatment. Moreover, there were significant differences in serum IL-4, IL-21 and BAFF between patients and controls. CONCLUSION: The overactivation of TFH cells may contribute to the immunopathogenesis of pediatric ITP. IL-21 and IL-4 serum levels may affect the differentiation of TFH cells in ITP patients. The aberrant balance between BAFFR-BAFF/TACI-BAFF may be a factor that caused the persistent high expression of ICOSL in pediatric cITP, which consequently lead to the over activation of TFH cells in pediatric cITP. PMID- 27667164 TI - Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells. AB - Hepcidin is the key regulator of systemic iron homeostasis. The iron-sensing mechanisms and the role of intracellular iron in modulating hepatic hepcidin secretion are unclear. Therefore, we created a novel cell line, recombinant-TfR1 HepG2, expressing iron-response-element-independent TFRC mRNA to promote cellular iron-overload and examined the effect of excess holotransferrin (5g/L) on cell surface TfR1, iron content, hepcidin secretion and mRNA expressions of TFRC, HAMP, SLC40A1, HFE and TFR2. Results showed that the recombinant cells exceeded levels of cell-surface TfR1 in wild-type cells under basal (2.8-fold; p<0.03) and holotransferrin-supplemented conditions for 24h and 48h (4.4- and 7.5-fold, respectively; p<0.01). Also, these cells showed higher intracellular iron content than wild-type cells under basal (3-fold; p<0.03) and holotransferrin supplemented conditions (6.6-fold at 4h; p<0.01). However, hepcidin secretion was not higher than wild-type cells. Moreover, holotransferrin treatment to recombinant cells did not elevate HAMP responses compared to untreated or wild type cells. In conclusion, increased intracellular iron content in recombinant cells did not increase hepcidin responses compared to wild-type cells, resembling hemochromatosis. Furthermore, TFR2 expression altered within 4h of treatment, while HFE expression altered later at 24h and 48h, suggesting that TFR2 may function prior to HFE in HAMP regulation. PMID- 27667167 TI - The disappearance of acute erythroid leukemia: An act of legerdemain at the World Health Organization. PMID- 27667165 TI - A novel pathogenic mutation in RPL11 identified in a patient diagnosed with diamond Blackfan anemia as a young adult. PMID- 27667166 TI - The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5' untranslated exon 1. AB - The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5' untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G>C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G>T 5' UTR variant inhibits translation of PPOX mRNA and c.1-176G>A splicing variant causes 4bp deletion in 5' UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5' untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria. PMID- 27667168 TI - Conditioned medium from human umbilical vein endothelial cells markedly improves the proliferation and differentiation of circulating endothelial progenitors. AB - Circulating endothelial progenitor cells (EPCs) have been suggested as a precious source for generating functionally competent endothelial cells (ECs), candidate for various clinical applications. However, the paucity of these progenitor cells and the technical difficulties for their in vitro growth represent a main limitation to their use. In the present study we hypothesized that the paracrine effects of human umbilical vein endothelial cells (HUVECs) may improve endothelial cell generation from cord blood (CB) EPCs. In line with this hypothesis we showed that HUVEC conditioned medium (CM) or co-culture with HUVECs markedly improved the proliferation and differentiation and delayed the senescence of CB EPCs. The endothelial-promoting effect of CM seems to be related to smaller vesicles including exosomes (sEV/exo) contained in this medium and transferred to CB CD34(+) EPCs: in fact, purified preparations of sEV/exo isolated from CM mimicked the effect of CM to sustain endothelial formation. These observations provided the interesting indication that mature ECs exert a stimulatory effect on endothelial cell differentiation from CD34(+) cells. PMID- 27667169 TI - AEG-1 promotes mesenchymal transition through the activation of Rho GTPases in human glioblastoma cells. AB - Despite growing evidence indicating that astrocyte elevated gene-1 (AEG-1) plays pivotal roles in tumor progression in various types of human cancers including brain tumors; to date, its role in the regulation of mesenchymal transition is not clear in glioblastoma. In the present study, we investigated the contribution of AEG-1 to stress fiber formation and then the acquisition of mesenchymal characteristics of glioblastoma cells. Gain- and loss-of-function studies in normal immortalized primary human fetal astrocytes (IM-PHFAs) and glioblastoma cells revealed that overexpression of AEG-1 increased expression of mesenchymal markers including N-cadherin and two mesenchymal transition-inducing transcription factors ZEB1 and Slug but decreased epithelial markers E-cadherin and ZO-1. In addition, knockdown of AEG-1 suppressed invasive ability and migration of glioblastoma cells. Overexpression of AEG-1 also induced stress fiber formation and activated the Rho GTPase signaling pathways in glioblastoma cells. Consistently, treatment with an RhoA inhibitor decreased AEG-1-mediated stress fiber formation in glioblastoma cells. Collectively, our findings suggest that AEG-1 promotes mesenchymal transition in glioblastoma through the regulation of the Rho signaling pathway, resulting in tumor invasion, a primary characteristic of malignant brain tumors. PMID- 27667170 TI - Deinococcus budaensis sp. nov., a mesophilic species isolated from a biofilm sample of a hydrothermal spring cave. AB - Following the exposure of a biofilm sample from a hydrothermal spring cave (Gellert Hill, Budapest, Hungary) to gamma radiation, a strain designated FeSTC15 38T was isolated and studied by polyphasic taxonomic methods. The spherical shaped cells stained Gram-negative, and were aerobic and non-motile. The pH range for growth was pH 6.0-9.0, with an optimum at pH 7.0. The temperature range for growth was 20-37 degrees C, with an optimum at 28 degrees C. Phylogenetic analysis based on the 16S rRNA gene sequence of the isolate indicated that the organism belongs to the genus Deinococcus. The highest sequence similarities appeared with Deinococcus hopiensis KR-140T (94.1 %), Deinococcus aquaticus PB314T (93.3 %) and Deinococcus aerophilus 5516T-11T (92.7 %). The DNA G+C content of the novel strain was 68.2 mol%. The predominant fatty acids (>10 %) were iso-C16 : 0 and C16 : 1omega7c, and the cell-wall peptidoglycan type was A3beta l-Orn-Gly2-3, corroborating the assignment of the strain to the genus Deinococcus. Strain FeSTC15-38T contained MK-8 as the major menaquinone and several unidentified phospholipids, glycolipids and phosphoglycolipids. Resistance to gamma radiation (D10) of strain FeSTC15-38T was <3.0 kGy. According to phenotypic and genotypic data, strain FeSTC15-38T represents a novel species for which the name Deinococcus budaensis sp. nov. is proposed. The type strain is FeSTC15-38T (=NCAIM B.02630T=DSM 101791T). PMID- 27667173 TI - Combined oridonin with cetuximab treatment shows synergistic anticancer effects on laryngeal squamous cell carcinoma: involvement of inhibition of EGFR and activation of reactive oxygen species-mediated JNK pathway. AB - Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is expressed at high levels in a large proportion of laryngeal squamous cell carcinoma (LSCC). Cetuximab (Cet), an anti-EGFR monoclonal antibody, has limited clinical outcome for patients with head and neck squamous cell carcinoma. Our previous studies showed that oridonin (ORI), a natural and safe kaurene diterpenoid isolated from Rabdosia rubescens, inhibited cell growth in HEp-2 cells through inhibition of EGFR phosphorylation. The aim of the present study was to determine whether ORI could improve the anticancer efficacy of Cet on LSCC. We observed that the combination with Cet and ORI synergistically inhibited cell growth associated with Fas-mediated apoptosis and G2/M phase arrest in two LSCC cell lines (HEp-2 and Tu212 cells). Moreover, combination treatment caused cell death associated with suppression of p-EGFR and activation of reactive oxygen species (ROS)-mediated JNK pathway. In nude mice bearing HEp-2 xenografts, ORI plus Cet caused a significant tumor regression through induction of apoptosis and inhibition of proliferation with no side-effect. Together, our findings suggest that the combination of ORI and Cet has the potential to enhance tumor responses and may significantly improve therapeutic outcomes in LSCC. PMID- 27667172 TI - Functional characterization of PhoPR two component system and its implication in regulating phosphate homeostasis in Bacillus anthracis. AB - BACKGROUND: Recent report on importance of phosphate starvation (PS) in Bacillus anthracis (BA) pathogenesis warrants further investigation of the underlying regulatory mechanism. Potential role of PhoPR two component system (TCS) in phosphate homeostasis and virulence of several pathogens necessitates the study of annotated PhoPR in BA. METHODS: Expression of phoP and phoR was analyzed using qRT-PCR. PhoPR was characterized biochemically. DNA-protein interaction was analyzed by EMSA. Docking was done to predict PhoPR interacting residues with further validation by mutational studies. pHCMC05 was used to overexpress PhoP in BA. RESULTS: In silico analysis revealed Bas4483-4484, as putative PhoR-PhoP. Their expression was decreased with increasing phosphate concentration reflecting some role in PS. Both PhoP (response regulator) and PhoR (histidine kinase) showed characteristic property of TCS i.e., autophosphorylation and phosphotransfer. PhoR showed both kinase and phosphatase activity. PhoP bound with promoter of PS marker genes. In silico and in vitro analysis revealed role of PhoRH370 and PhoPD10, PhoPD53, PhoPM55 in PhoPR interaction. Challenge studies showed decreased survival of mice infected with BApHCMC05-PhoP. CONCLUSION: This study affirms that PhoPR forms functional TCS which is upregulated under PS. PhoP binding with promoter of PS marker genes indicates its possible role in regulating PS response. Low survival of mice infected with BApHCMC05-PhoP suggests its role in BA virulence. GENERAL SIGNIFICANCE: Considering the significance of PS in BA infection, possible role of PhoPR in its regulation and exclusive presence of TCS in prokaryotes, PhoP can be proposed as potential drug target against anthrax. PMID- 27667171 TI - Filling the Void: Proximity-Based Labeling of Proteins in Living Cells. AB - There are inherent limitations with traditional methods to study protein behavior or to determine the constituency of proteins in discrete subcellular compartments. In response to these limitations, several methods have recently been developed that use proximity-dependent labeling. By fusing proteins to enzymes that generate reactive molecules, most commonly biotin, proximate proteins are covalently labeled to enable their isolation and identification. In this review we describe current methods for proximity-dependent labeling in living cells and discuss their applications and future use in the study of protein behavior. PMID- 27667174 TI - The cotton buds beach: Marine litter assessment along the Tyrrhenian coast of central Italy following the marine strategy framework directive criteria. AB - We assessed the annual accumulation rates of beach litter on the Tyrrhenian coast of central Italy, providing the characterization of litter following European standardized guidelines. Three different sites of a beach were sampled seasonally from spring 2014 to winter 2015. A total of 31,739 items were removed and classified into 103 categories. Plastic represented the majority (94.4%) of the collected items. We detected temporal and spatial differences in the abundance and composition of litter between seasons and between sites. Furthermore, we found that plastic cotton bud sticks composed >30% of the total amount of litter and, together with plastic and polystyrene pieces, made up >70% of the total items. Finally, our results led us to propose that the most effective strategy to reduce litter pollution is to devise specific management procedures focusing on the most abundant items. PMID- 27667175 TI - Assessing benthic ecological impacts of bottom aquaculture using macrofaunal assemblages. AB - Bottom aquaculture of bivalves is a high-yield culture method, which is increasingly adopted by shellfish farmers worldwide. However, the effects of bottom aquaculture on benthic ecosystems are not well-known. Manila clam (Ruditapes philippinarum), is a widely distributed bottom aquaculture mollusk species. To assess the ecological impacts of Manila clam bottom aquaculture, clams and other macrofaunal assemblages were investigated during four cruises (July and November 2011, February and May 2012) at six sampling sites in Jiaozhou Bay, China. Correlation analysis showed that macrofaunal assemblages had significant negative correlations with the abundance of Manila clams. However, according to the results of several biotic indices, a low disturbance was detected by Manila clam bottom aquaculture. In conclusion, AMBI (AZTI'S Marine Biotic Index) and M-AMBI (Multivariate AZTI Marine Biotic Index) indices are more suitable for assessing ecological quality than polychaete/amphipod ratios when the disturbance is slight, such as at a bivalve bottom aquaculture. PMID- 27667177 TI - Twist in the Tail: Escape from HIV Neutralising Antibodies at a Single Site Confers Broad Susceptibility to Others. PMID- 27667176 TI - Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma. AB - Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2) as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes. PMID- 27667178 TI - Improvement of vascular function by magnetic nanoparticle-assisted circumferential gene transfer into the native endothelium. AB - Gene therapy is a promising approach for chronic disorders that require continuous treatment such as cardiovascular disease. Overexpression of vasoprotective genes has generated encouraging results in animal models, but not in clinical trials. One major problem in humans is the delivery of sufficient amounts of genetic vectors to the endothelium which is impeded by blood flow, whereas prolonged stop-flow conditions impose the risk of ischemia. In the current study we have therefore developed a strategy for the efficient circumferential lentiviral gene transfer in the native endothelium under constant flow conditions. For that purpose we perfused vessels that were exposed to specially designed magnetic fields with complexes of lentivirus and magnetic nanoparticles thereby enabling overexpression of therapeutic genes such as endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). This treatment enhanced NO and VEGF production in the transduced endothelium and resulted in a reduction of vascular tone and increased angiogenesis. Thus, the combination of MNPs with magnetic fields is an innovative strategy for site-specific and efficient vascular gene therapy. PMID- 27667180 TI - Good things come in small packages: Overcoming challenges to harness extracellular vesicles for therapeutic delivery. AB - Extracellular vesicles (EVs) hold great promise as potential therapeutic carriers. EVs are biologically active, intrinsically transporting cargo between cells. Moreover, they can be loaded with specific cargo for distribution and/or engineered to achieve enhanced uptake. Although studies have already demonstrated therapeutic delivery using EVs, various challenges must be overcome before EV technology is ready for the clinic. Since the properties of EVs are dependent upon their cell of origin and the conditions of their formation, establishing clear characterization practices is essential to ensuring reproducibility and safety. Identifying methods for mass production of EVs is crucial for achieving high EV yields necessary for clinical trials. This review introduces current theory behind EV formation and function, describes the latest methods for characterization and mass production, and discusses future opportunities for extracellular vesicles in therapeutic delivery. PMID- 27667179 TI - Ultrasound-triggered drug delivery for cancer treatment using drug delivery systems: From theoretical considerations to practical applications. AB - Ultrasound-triggered drug delivery is now becoming a mature technology with first patients enrolling in clinical trials. Having a clear overview of the field is complicated as it mixes ultrasound physics and biological effects, particle formulation, and pharmacokinetics and biodistribution. The scope of this review is to move from basics to the latest developments of combined techniques using ultrasound for triggering drug release. Generalities on ultrasound are first given to better understand the parameters on which the clinician can operate to modulate the amount of delivered energy. Ultrasound effects on biological tissues such as thermal effects, mechanical effects and radiation forces are also presented. The second part of this review deals with the combination of ultrasound and drug delivery systems to enhance the efficacy of current cancer treatment. The in vivo behavior of drug delivery systems and how ultrasounds can be combined to improve treatment efficacy are detailed. The example of ThermoDox(r), a new formulation of thermosensitive liposomes undergoing a phase III clinical trial, is particularly discussed on the basis of the available clinical data. Through the present article, researchers will be able to better grasp the different levels of complexity when designing an efficient formulation to be combined with ultrasound. PMID- 27667181 TI - Dietary antioxidant capacity and risk for stroke in a prospective cohort study of Swedish men and women. AB - OBJECTIVE: Both observational studies and randomized trials have shown that a diet rich in antioxidants can reduce systemic inflammation and oxidative stress, two conditions that, together with obesity and smoking, are established risk factors for stroke. However, the association between antioxidant intake and risk for stroke is poorly understood, particularly when studying possible interaction with sex. We investigated the relationship of nonenzymatic antioxidant capacity (NEAC) on risk for stroke in a large Swedish prospective cohort. METHODS: The cohort study included 34 555 men and women from the Swedish National March Cohort. NEAC was assessed using a detailed food frequency questionnaire, collected at baseline. We achieved complete follow-up from enrollment in 1997 through 2010 by record linkage to nationwide registers. We identified 1186 incident cases of a first stroke, of which 860 were ischemic, 201 hemorrhagic, and 125 unspecified. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CIs). RESULTS: Compared with women in the lowest quartile of NEAC, women in the highest quartile had a 27% lower incidence of total stroke (HR, 0.73; 95% CI, 0.53-0.99; Ptrend = 0.03) and 35% lower incidence of ischemic stroke (HR, 0.65; 95% CI, 0.43 0.99; Ptrend = 0.01). Among men, the relationship between NEAC and risk for stroke was not statistically significant and all HRs were close to unity. CONCLUSION: Findings from the present study suggest that dietary antioxidant capacity from different foods and beverages is inversely associated with risk for stroke, more specifically ischemic stroke, in women. PMID- 27667182 TI - Resveratrol attenuates myocardial ischemia/reperfusion injury through up regulation of vascular endothelial growth factor B. AB - The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3beta. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3beta, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy. PMID- 27667183 TI - Intracolonic hydrogen sulfide lowers blood pressure in rats. AB - Research suggests that hydrogen sulfide (H2S) is an important biological mediator involved in various physiological processes including the regulation of arterial blood pressure (BP). Although H2S is abundant in the colon, the effects of gut derived H2S on the circulatory system have not yet been investigated. We studied the effects of intracolonic administration of Na2S, a H2S donor, on systemic hemodynamics. Hemodynamics were recorded in anesthetized, normotensive Wistar Kyoto and spontaneously hypertensive rats at baseline and after intracolonic injection of either saline (controls) or Na2S.9H2O saline solution at a dose range of 10-300 mg/kg of BW. The H2S donor produced a significant, dose-dependent decrease in mean arterial blood pressure (MABP), which lasted several times longer than previously reported after parenteral infusions (>90 min). The effect was more pronounced in hypertensive than in normotensive rats. The Na2S-induced decrease in MABP was reduced by pretreatment with glibenclamide, an inhibitor of ATP-sensitive potassium-channels. Na2S did not affect mesenteric vein blood flow. Rats treated with Na2S showed increased portal blood levels of thiosulfate and sulfane sulfur, products of H2S oxidation. In contrast, rats treated with neomycin, an antibiotic, showed significantly decreased levels of thiosulfate and sulfane sulfur, and a tendency for greater hypotensive response to Na2S. The H2S donor decreased heart rate but did not affect ECG morphology and QTc interval. In conclusion the gut-derived H2S may contribute to the control of BP and may be one of the links between gut microbiota and hypertension. Furthermore, gut-derived H2S may be a therapeutic target in hypertension. PMID- 27667184 TI - Episodic Ataxias: Clinical and Genetic Features. AB - Episodic ataxia (EA) is a clinically heterogeneous group of disorders that are characterized by recurrent spells of truncal ataxia and incoordination lasting minutes to hours. Most have an autosomal dominant inheritance pattern. To date, 8 subtypes have been defined according to clinical and genetic characteristics, and five genes are known to be linked to EAs. Both EA1 and EA2, which are caused by mutations in KCNA1 and CACNA1A, account for the majority of EA, but many patients with no identified mutations still exhibit EA-like clinical features. Furthermore, genetically confirmed EAs have mostly been identified in Caucasian families. In this article, we review the current knowledge on the clinical and genetic characteristics of EAs. Additionally, we summarize the phenotypic features of the genetically confirmed EA2 families in Korea. PMID- 27667187 TI - The MMSE and MoCA for Screening Cognitive Impairment in Less Educated Patients with Parkinson's Disease. AB - OBJECTIVE: To explore whether the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) can be used to screen for dementia or mild cognitive impairment (MCI) in less educated patients with Parkinson's disease (PD). METHODS: We reviewed the medical records of PD patients who had taken the Korean MMSE (K-MMSE), Korean MoCA (K-MoCA), and comprehensive neuropsychological tests. Predictive values of the K-MMSE and K-MoCA for dementia or MCI were analyzed in groups divided by educational level. RESULTS: The discriminative powers of the K-MMSE and K-MoCA were excellent [area under the curve (AUC) 0.86 0.97] for detecting dementia but not for detecting MCI (AUC 0.64-0.85). The optimal screening cutoff values of both tests increased with educational level for dementia (K-MMSE < 15 for illiterate, < 20 for 0.5-3 years of education, < 23 for 4-6 years, < 25 for 7-9 years, and < 26 for 10 years or more; K-MoCA < 7 for illiterate, < 13 for 0.5-3 years, < 16 for 4-6 years, < 19 for 7-9 years, < 20 for 10 years or more) and MCI (K-MMSE < 19 for illiterate, < 26 for 0.5-3 years, < 27 for 4-6 years, < 28 for 7-9 years, and < 29 for 10 years or more; K-MoCA < 13 for illiterate, < 21 for 0.5-3 years, < 23 for 4-6 years, < 25 for 7-9 years, < 26 for 10 years or more). CONCLUSION: Both MMSE and MoCA can be used to screen for dementia in patients with PD, regardless of educational level; however, neither test is sufficient to discriminate MCI from normal cognition without additional information. PMID- 27667185 TI - Applications of CRISPR/Cas9 for Gene Editing in Hereditary Movement Disorders. AB - Gene therapy is a potential therapeutic strategy for treating hereditary movement disorders, including hereditary ataxia, dystonia, Huntington's disease, and Parkinson's disease. Genome editing is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome using modified nucleases. Recently, clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 (CRISPR/Cas9) has been used as an essential tool in biotechnology. Cas9 is an RNA-guided DNA endonuclease enzyme that was originally associated with the adaptive immune system of Streptococcus pyogenes and is now being utilized as a genome editing tool to induce double strand breaks in DNA. CRISPR/Cas9 has advantages in terms of clinical applicability over other genome editing technologies such as zinc-finger nucleases and transcription activator like effector nucleases because of easy in vivo delivery. Here, we review and discuss the applicability of CRISPR/Cas9 to preclinical studies or gene therapy in hereditary movement disorders. PMID- 27667186 TI - Cognition and Visit-to-Visit Variability of Blood Pressure and Heart Rate in De Novo Patients with Parkinson's Disease. AB - OBJECTIVE: We sought to identify whether the characteristics of long-term visit to-visit blood pressure (BP) and heart rate (HR) are related to baseline cognitive profiles in, Parkinson's disease (PD). METHODS: We selected drug-naive PD patients who visited our hospital at least 10 times with a baseline assessment of the Seoul neuropsychological battery. BP and HR were measured at each visit, and the variability of the systolic BP/diastolic BP (DBP) and HR was derived from the parameters of serial 10 office visits. Mild cognitive impairment (MCI) in PD patients was determined according to the proposed criteria with a cut-off value of z-score <= -2. RESULTS: Forty-seven patients with PD (mean follow-up duration = 22.3 months) were enrolled in the study. Compared with non-MCI PD patients, MCI PD patients revealed a significant increase in HR and/or variability in DBP. CONCLUSION: This exploratory study showed that baseline cognition in drug-naive PD patients might be related to the visit-to-visit variability of DBP and/or HR. PMID- 27667188 TI - Falls and Their Associated Risks in Parkinson's Disease Patients in Nigeria. AB - OBJECTIVE: Falls are a devastating consequence of Parkinson's disease (PD) and are due to motor imbalance. However, the frequency of falls and their risk factors among Nigerians with PD is not known despite the significant increase in PD cases in the country. To assess fall risk factors and frequency in Nigerian PD patients. METHODS: Using an analytical design to compare falling versus non falling patients, 81 PD patients were assessed for clinical factors, frequency of falls, and candidate risk factors for falls according to the Tinetti Balance and Gait, Unified Parkinson's Disease Rating Scale subsection 1, and Timed Up and Go Tests. Descriptive, bivariate, and multivariate analyses were performed at the 95% confidence level. RESULTS: The mean age of participants was 65.6 +/- 9.7 years. Falls were about three times (p < 0.001) more common in PD patients. Of the falling patients, 67.7% sustained injuries, 67.7% had recurrent falls and 44.9% admitted to having a fear of falling. The independent statistical predictors of fall were fear of falling [odds ratio (OR): 3.86], disease severity (OR: 1.09) and disease duration (OR: 1.01). CONCLUSION: The frequency of falls in PD patients was significantly higher when compared with the healthy adult population, and the modifiable predictor was fear of falling with a potential to significantly reduce falls when strategically addressed. PMID- 27667189 TI - Survival of Korean Huntington's Disease Patients. AB - OBJECTIVE: The survival of Huntington's disease (HD) patients is reported to be 15-20 years. However, most studies on the survival of HD have been conducted in patients without genetic confirmation with the possible inclusion of non-HD patients, and all studies have been conducted in Western countries. The survival of patients with HD in East Asia, where its prevalence is 10-50-fold lower compared with Western populations, has not yet been reported. METHODS: Forty seven genetically confirmed Korean HD patients from independent families were included in this retrospective medical record review study. RESULTS: The mean age at onset among the 47 patients was 46.1 +/- 14.0 years. At the time of data collection, 25 patients had died, and these patients had a mean age at death of 57.8 +/- 13.7 years. The Kaplan-Meier estimate of the median survival from onset in the 47 patients was 14.5 years (95% confidence interval: 12.3-16.6). None of the following factors were associated with the survival time in the univariate Cox regression analysis: gender, age at onset, normal CAG repeat size, mutant CAG repeat size, and the absence or presence of non-motor symptoms at onset. CONCLUSION: This is the first Asian study on survival in HD patients. Survival in Korean HD patients may be shorter than that reported for Western populations, or at least is in the lower range of expected survival. A larger longitudinal observation study is needed to confirm the results found in this study. PMID- 27667190 TI - A general and efficient strategy for generating the stable enzymes. AB - The local flexibility of an enzyme's active center plays pivotal roles in catalysis, however, little is known about how the flexibility of these flexible residues affects stability. In this study, we proposed an active center stabilization (ACS) strategy to improve the kinetic thermostability of Candida rugosa lipase1. Based on the B-factor ranking at the region ~10 A within the catalytic Ser209, 18 residues were selected for site-saturation mutagenesis. Based on three-tier high-throughput screening and ordered recombination mutagenesis, the mutant VarB3 (F344I/F434Y/F133Y/F121Y) was shown to be the most stable, with a 40-fold longer in half-life at 60 degrees C and a 12.7 degrees C higher Tm value than that of the wild type, without a decrease in catalytic activity. Further analysis of enzymes with different structural complexities revealed that focusing mutations on the flexible residues within around 10 A of the catalytic residue might increase the success rate for enzyme stabilization. In summary, this study identifies a panel of flexible residues within the active center that affect enzyme stability. This finding not only provides clues regarding the molecular evolution of enzyme stability but also indicates that ACS is a general and efficient strategy for exploring the functional robustness of enzymes for industrial applications. PMID- 27667192 TI - Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-A case-control study based on secondary data. AB - BACKGROUND: Several studies point to an elevated risk for cardiovascular diseases induced by traffic noise. AIMS: We examined the association between aircraft, road traffic and railway noise and heart failure or hypertensive heart disease (HHD) in a large case-control study. METHODS: The study population consisted of individuals that were insured by three large statutory health insurance funds in the Rhine-Main area of Germany. Based on insurance claims and prescription data, 104,145 cases of heart failure or HHD diagnosed 2006-10 were identified and compared with 654,172 control subjects. Address-specific exposure to aircraft, road and railway traffic noise in 2005 was estimated. Odds Ratios were calculated using logistic regression analysis, adjusted for age, sex, local proportion of persons receiving unemployment benefits, and individual socioeconomic status (available for 39% of the individuals). RESULTS: A statistically significant linear exposure-risk relationship with heart failure or hypertensive heart disease was found for aircraft traffic noise (1.6% risk increase per 10dB increase in the 24-h continuous noise level; 95% CI 0.3-3.0%), road traffic noise (2.4% per 10dB; 95% CI 1.6-3.2%), and railway noise (3.1% per 10dB; 95% CI 2.2 4.1%). For individuals with 24-h continuous aircraft noise levels <40dB and nightly maximum aircraft noise levels exceeding 50dB six or more times, a significantly increased risk was observed. In general, risks of HHD were considerably higher than the risks of heart failure. CONCLUSIONS: Regarding the high prevalence of traffic noise from various sources, even low risk increases for frequent diseases are relevant for the population as a whole. PMID- 27667191 TI - Non lethal Raine syndrome and differential diagnosis. AB - Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form. PMID- 27667194 TI - Effects of polysaccharides isolated from Inonotus obliquus against hydrogen peroxide-induced oxidative damage in RINm5F pancreatic beta-cells. AB - The purpose of the present study was to elucidate the cytoprotective effects of polysaccharides isolated from Inonotus obliquus. The polysaccharides were extracted from the fruiting body of I. obliquus (PFIO) and the liquid culture broth of I. obliquus (PLIO). The effects of PFIO and PLIO on hydrogen peroxide (H2O2)-induced oxidative damage of RINm5F pancreatic beta-cells were comparatively investigated using an MTT assay, immunofluorescent staining, flow cytometry, and western blot analyses in vitro. The results of the present study demonstrated that treatment with PFIO and PLIO decreased DNA fragmentation and the rate of apoptosis. In addition, pretreatment of cells with PFIO and PLIO prior to H2O2 exposure resulted in increased insulin secretion and scavenging activity for intracellular reactive oxygen species, as compared with treatment with H2O2 alone. The results of the present study suggested that PFIO and PLIO may exert protective effects against H2O2-induced oxidative stress via the regulation of mitogen-activated protein kinases, nuclear factor-kappaB and apoptotic proteins. Therefore, PFIO and PLIO may have potential merit as a medicinal food for the prevention of diabetes. PMID- 27667193 TI - Satellite RNAs promote pancreatic oncogenic processes via the dysfunction of YBX1. AB - Highly repetitive tandem arrays at the centromeric and pericentromeric regions in chromosomes, previously considered silent, are actively transcribed, particularly in cancer. This aberrant expression occurs even in K-ras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To examine the biological roles of the satellite RNAs in carcinogenesis, we construct mouse PanIN-derived cells expressing major satellite (MajSAT) RNA and show increased malignant properties. We find an increase in frequency of chromosomal instability and point mutations in both genomic and mitochondrial DNA. We identify Y-box binding protein 1 (YBX1) as a protein that binds to MajSAT RNA. MajSAT RNA inhibits the nuclear translocation of YBX1 under stress conditions, thus reducing its DNA-damage repair function. The forced expression of YBX1 significantly decreases the aberrant phenotypes. These findings indicate that during the early stage of cancer development, satellite transcripts may act as 'intrinsic mutagens' by inducing YBX1 dysfunction, which may be crucial in oncogenic processes. PMID- 27667196 TI - In vitro glycation of bovine liver catalase by glucose and fructose and antigycation effects of aspirin: a spectroscopic study. PMID- 27667195 TI - New frontiers in human assisted reproduction - from research to clinical practice: Several considerations (Review). AB - In the era of very late, or advanced, motherhood, in which 'egg banks', 'social' egg-freezing, egg donation and surrogacy represent a potential solution to a number of obstacles to human reproduction, what is the role of scientists and clinicians involved in assisted reproduction? In light of the apprehension that, in the future, through fertility treatment infertility may be passed on to the offspring, boundaries of medical vs. 'social' infertility are being created. Scientists and clinicians are joining forces in a synergistic effort to improve the effectiveness of infertility care by introducing novel therapeutic protocols with the intent of customising care and improving cost-effectiveness, testing novel drugs and formulations, and searching for novel markers (for estimating biological age) and nomograms (to optimise the yield of a controlled ovarian hyperstimulation cycle). On the other hand, political, social and health institutions are doing little to educate young women with respect to disinformation and to increase their awareness regarding age as the predominant factor that contributes towards the decline in fertility. Nevertheless, despite the great advances that have been made, 38 years after the birth of the first baby via in vitro fertilisation, the intricate road leading from the antral follicle to the fully developed baby continues to be designated as being too 'expensive', 'empirical', 'mysterious' or 'bound by ethics', with few significant improvements in terms of real cost-effectiveness. PMID- 27667197 TI - Hemocompatible and immune-safe library of citrem-phospholipid liquid crystalline nanoplatforms. PMID- 27667198 TI - Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. AB - The cytochrome (cyt) bc1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Qi-site of the cyt bc1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Qi-site to facilitate binding of half-protonated semiquinone - a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Qi-site. PMID- 27667200 TI - Access to Essential Medications During Disaster Events. PMID- 27667201 TI - Recent Advances in Analysis of Pesticides in Food and Drink Samples Using LPME Techniques Coupled to GC-MS and LC-MS: a Review. AB - Food quality and food safety are major challenges affecting agricultural and industrial aspects of production. Many contaminants from different sources contaminate foods and drinks, leading to disastrous health problems like gene mutations and cancer. Previously, many different methods have been used for the analysis of these contaminants. Liquid-liquid extraction (LLE) has been the most well-known conventional technique used, but its limitations are its tediousness, time required, and the use of large quantities of toxic organic solvents. These limitations have led to the search for other, efficient techniques that are more environmentally friendly. Hence, this review highlights recent advances in liquid phase (single-drop, hollow fiber, and dispersive liquid-liquid) microextraction procedures for food and drink analyses. Such modifications can be justified for solving limitations associated with the traditional LLE method. The objective of this review is to serve as a reference platform for providing effective management tools for solving problems of pollution, clean-up, and control of food quality and safety globally. PMID- 27667199 TI - Identification and comparative analysis of the microRNA transcriptome in roots of two contrasting tobacco genotypes in response to cadmium stress. AB - Tobacco (Nicotiana tabacum L.) is more acclimated to cadmium (Cd) uptake and preferentially enriches Cd in leaves than other crops. MicroRNAs (miRNAs) play crucial roles in regulating expression of various stress response genes in plants. However, genome-wide expression of miRNAs and their target genes in response to Cd stress in tobacco are still unknown. Here, miRNA high-throughput sequencing technology was performed using two contrasting tobacco genotypes Guiyan 1 and Yunyan 2 of Cd-sensitive and tolerance. Comprehensive analysis of miRNA expression profiles in control and Cd treated plants identified 72 known (27 families) and 14 novel differentially expressed miRNAs in the two genotypes. Among them, 28 known (14 families) and 5 novel miRNAs were considered as Cd tolerance associated miRNAs, which mainly involved in cell growth, ion homeostasis, stress defense, antioxidant and hormone signaling. Finally, a hypothetical model of Cd tolerance mechanism in Yunyan 2 was presented. Our findings suggest that some miRNAs and their target genes and pathways may play critical roles in Cd tolerance. PMID- 27667202 TI - The relationships between OHS prevention costs, safety performance, employee satisfaction and accident costs. AB - Little is known about the costs of safety. A literature review conducted for this study indicates there is a lack of survey-based research dealing with the effects of occupational health and safety (OHS) prevention costs. To close this gap in the literature, this study investigates the interwoven relationships between OHS prevention costs, employee satisfaction, OHS performance and accident costs. Data were collected from 159 OHS management system 18001-certified firms operating in Turkey and analyzed through structural equation modeling. The findings indicate that OHS prevention costs have a significant positive effect on safety performance, employee satisfaction and accident costs savings; employee satisfaction has a significant positive effect on accident costs savings; and occupational safety performance has a significant positive effect on employee satisfaction and accident costs savings. Also, the results indicate that safety performance and employee satisfaction leverage the relationship between prevention costs and accident costs. PMID- 27667203 TI - Berry phase and band structure analysis of the Weyl semimetal NbP. AB - Weyl semimetals are often considered the 3D-analogon of graphene or topological insulators. The evaluation of quantum oscillations in these systems remains challenging because there are often multiple conduction bands. We observe de Haas van Alphen oscillations with several frequencies in a single crystal of the Weyl semimetal niobium phosphide. For each fundamental crystal axis, we can fit the raw data to a superposition of sinusoidal functions, which enables us to calculate the characteristic parameters of all individual bulk conduction bands using Fourier transform with an analysis of the temperature and magnetic field dependent oscillation amplitude decay. Our experimental results indicate that the band structure consists of Dirac bands with low cyclotron mass, a non-trivial Berry phase and parabolic bands with a higher effective mass and trivial Berry phase. PMID- 27667205 TI - Editorial. AB - There has been a recent and fairly dramatic growth of academic appointments in nursing: in the United Kingdom there are now professors of nursing, nursing studies, nursing education and nursing research. Sadly, in the area of central importance, nursing practice, there has been no such academic development. PMID- 27667204 TI - In vitro and in vivo study of additive manufactured porous Ti6Al4V scaffolds for repairing bone defects. AB - Metallic implants with a low effective modulus can provide early load-bearing and reduce stress shielding, which is favorable for increasing in vivo life-span. In this research, porous Ti6Al4V scaffolds with three pore sizes (300~400, 400~500, and 500~700 MUm) were manufactured by Electron Beam Melting, with an elastic modulus range of 3.7 to 1.7 GPa. Cytocompatibility in vitro and osseointegration ability in vivo of scaffolds were assessed. hBMSCs numbers increased on all porous scaffolds over time. The group with intended pore sizes of 300 to 400 MUm was significantly higher than that of the other two porous scaffolds at days 5 and 7. This group also had higher ALP activity at day 7 in osteogenic differentiation experiment. The scaffold with pore size of 300 to 400 MUm was implanted into a 30-mm segmental defect of goat metatarsus. In vivo evaluations indicated that the depth of bone ingrowth increased over time and no implant dislocation occurred during the experiment. Based on its better cytocompatibility and favorable bone ingrowth, the present data showed the capability of the additive manufactured porous Ti6Al4V scaffold with an intended pore size of 300 to 400 MUm for large segmental bone defects. PMID- 27667207 TI - Staff and cash cuts blamed for cancellations. AB - Around one in ten operations were cancelled last year, with the blame falling mainly on lack of staff and money, the labour Party said this week. PMID- 27667208 TI - Government accused of backtracking over costs. AB - As hospitals gear up for possible Gulf War casualties, doubts have arisen over whether the Department of Health will keep its promise to reimburse health authorities for the extra cost. PMID- 27667206 TI - On these rocks... commitment to nurse education in the 1990s. AB - This article is a modified version of the public lecture given by June Clark to launch the UK's newest School of Health Care Studies at Middlesex Polytechnic on November 20 1990. PMID- 27667210 TI - Limited prescribing Bill launched in Parliament. AB - A Bill has been launched in Parliament aimed at allowing some nurses the power to prescribe from a limited list of supplies and drugs. PMID- 27667209 TI - 'Astonishing arrogance' angers nursing unions. AB - Angry nursing unions accused the Government of 'astonishing arrogance' and meanness after last week's announcement that the pay award will be staged for the second successive year. PMID- 27667211 TI - Cutbacks. AB - Elective surgery and orthopaedics have suffered most from the crisis in London's health service, where cuts have added to the country's longest waiting lists, a new report shows. The report by the Association of London Authorities and the Greater London Association of CHCs reveals that eight of the ten Inner London HAs have made cuts of more than L1 million this year. PMID- 27667213 TI - ? AB - A purchaser's perspective: Sue Gallagher. Wandsworth Health Authority Director of Health Care Standards, was one of the speakers at last week's Nursing Standard/Royal College of Nursing 'Countdown to change' conference in Birmingham. PMID- 27667212 TI - Commons report claims staff levels are too high. AB - Nurses in Northern Ireland are angry over a Commons report claiming that nurse staffing levels are too high. PMID- 27667214 TI - Nurses tell of bomb threats in Saudi. AB - Nurses returning from Saudi Arabia have spoken of the difficulties they had leaving the country and cautioned others to think seriously before going to work there during the war. PMID- 27667216 TI - Nurses must recover their 'moral frameworks'. AB - The world's first centre for nursing ethics was launched last week w'ith the aim of morally empowering nurses to challenge medico-scientific dominance. PMID- 27667215 TI - A survey of the nutritional adequacy of meals served and eaten by patients. AB - In July 1943, the 'Memorandum of hospital diet' published by the King Edward's Hospital Fund for London, stated: 'The food service should be regarded as one of the essential remedial services offered by hospital.' For elderly people food may be the highlight of the day. When its nutritional content is inadequate, this may be the cause of malady rather than health (1). PMID- 27667217 TI - Rally of support for Pink. AB - MPs have urged Stockport Health Authority to 'think again' and reinstate Graham Pink, the charge nurse found guilty of gross misconduct after his public campaign against understaffing at Stepping Hill Hospital. PMID- 27667220 TI - Low secondment patterns cause concern. AB - The English National Board has expressed its concern about the low numbers of community nurses seconded to post-registration district nursing and health visiting courses. PMID- 27667218 TI - ? AB - RCN General Secretary Christine Hancock has been appointed to the Management Committee of the King Edward's Hospital Fund for London. The appointment, which lasts for five years, also includes membership of the King's Fund's General Council. PMID- 27667221 TI - UK fails on child rights. AB - Britain's failure to ratify the United Nations Convention on the Rights of the Child has been criticised as 'inexcusable' and 'an indication of the low priority still accorded to children's rights', the National Summit for Children was told last week. PMID- 27667223 TI - RCN demands priority for flexible conversion. AB - The RCN has called on managers to encourage enrolled nurses to apply for posts at grade D and above and to support flexible conversion measures. PMID- 27667222 TI - Lack of income support distresses elderly patients. AB - Elderly patients in residential homes are being put under 'untold stress' by the Government's failure to increase income support substantially, claims the Independent Healthcare Association. PMID- 27667225 TI - Coalition discourages breast-milk substitutes. AB - A European Community draft directive on marketing breast-milk substitutes could lead to companies resuming unethical practices, the Baby Milk Action Coalition has warned. PMID- 27667224 TI - Nurses win special leave for family care. AB - Nurses have won the right to special leave for personal and family needs under new arrangements announced by Health Minister Virginia Bottomley last week. PMID- 27667226 TI - Sign language training for Glasgow nurses. AB - Outpatient nurses at Greater Glasgow hospitals are receiving special training in sign language so they can provide a better service for profoundly deaf patients. PMID- 27667227 TI - Scientific approach for cancer care. AB - One of the best weapons in the fight against professional 'burn out' is education, according to Gus de Haas, Director of Nurse Training from Tilburg, Holland. Speaking at a conference on a European core curriculum for postbasic cancer nursing, he told delegates from all over Europe that oncology nursing has aspects that make special training necessary, and that the philosophy of the curriculum should focus on the interaction between cancer patient and nurse. 'We should listen very carefully to the person who lives with the reality of having cancer,' he said. PMID- 27667228 TI - Government is 'running scared'. AB - The Government is 'running scared' of the competitive elements of its NHS reforms, health service managers heard last week. PMID- 27667229 TI - ? AB - Austria A new portable liquid oxygen device is being tested under clinical conditions in Vienna and Graz. It enables patients needing oxygen-enriched air to leave their beds and lead a 'relatively normal life'. PMID- 27667230 TI - The management of change on a Nursing Development Unit. AB - Given the current financial constraints within the health service, coupled with the increased impetus for ensuring that a quality service is delivered to each and every individual, it is vitally important to highlight one fact - that beneficial changes to nursing care are achievable by commitment alone without the need for added staff and money (although had these been made available, the process of change would certainly have been rendered less stressful and possibly more enjoyable). PMID- 27667233 TI - More research 'could save accident victims'. AB - Of the 14,500 people who the in Britain each year as a result of accidental injury, one in five lives could be saved if more was spent on research and training, according to a new medical charity, The Trauma Foundation. PMID- 27667234 TI - Test for albumin may detect kidney failure. AB - A new test for detecting minute traces of albumin in the urine of diabetic patients may allow earlier detection of those at risk of developing kidney failure. PMID- 27667231 TI - Parliament. AB - Stricter health safeguards for employees working with computer screens are being prepared by the Health and Safety Commission. PMID- 27667235 TI - Psychological therapies 'are inadequate'. AB - GPs wishing to refer patients for specialist treatment are faced with a 'confusing, fragmented and inadequate' array of psychological therapies available, according to a report from the British Psychological Society (BPS). PMID- 27667236 TI - Postnatal rise in mental illness, but not suicide. AB - Although studies indicate an increase in psychiatric illness among women after childbirth, the incidence of postnatal suicide is far lower than might be expected, according to a report in the British Medical Journal. PMID- 27667237 TI - Task allocation: A case of resistance to change? AB - In recent years, changes in nursing philosophy have led to the development of methods of work organisation which promote individualised nursing care. Awareness that routinised care has often meant a failure to meet the needs of individual patients can be traced back to early British nursing research ( 1 , 2 ). PMID- 27667238 TI - Treating congenital dislocation of the hip. AB - In children with dislocatable hips a 'wait and see' treatment strategy should be adopted, say researchers. PMID- 27667239 TI - New treatment strategy benefits liver cancer. AB - A new technique is showing promise in the treatment of liver cancer, researchers from the University of Michigan say. PMID- 27667240 TI - Heparin versus saline in infusion patency. AB - Physiological saline might be as effective as heparin in maintaining the patency of intermittent infusion devices. PMID- 27667242 TI - 'Real increase' in renal arteritis. AB - The incidence of renal arteritis has increased since the mid-1980s both in absolute numbers and as a proportion of acute glomerulonephritis, researchers from Leeds say. PMID- 27667241 TI - CPR learning not affected by anxiety. AB - Anxiety is not a bar to learning cardiopulmonary resuscitation (CPR) techniques and it should be offered to family members of patients with cardiac disease. PMID- 27667243 TI - An investigation of occupational stress among nurse tutors. AB - As most of us are aware from our own work-related experience, occupational stress is an inevitable part of our working lives and at low levels can actually act as a motivator to enhance performance. However, at higher levels it has adverse consequences ( 2 ). The cause and effects of stress are well documented by authors such as Cherniss ( 3 ), Cooper et al ( 1 ) and Fontana ( 4 ). PMID- 27667244 TI - Making nursing models relevant for the practising nurse. AB - For thousands of years the goal of nursing has been to provide nurturing 'care' in a manner which assists individuals or groups of people to reach an optimal level of health. This defines the uniqueness of nursing, ie the care by the nurse versus the 'cure' of the physician. The motivation of providing nurturing care is the same today for the critical care nurse in a modern intensive care unit as it was for the parent in a cave. PMID- 27667245 TI - Primary nursing: Accountability is the key to its mystery. AB - What is the key to unravel the mystery of primary nursing? Zander ( 1 ) notes that primary nursing's enormous potential and mystery remains so because of confusion about putting into practice its central concepts, especially that of accountability. PMID- 27667246 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Clare Ward, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX (Fax 081-423 3867). PMID- 27667248 TI - War preparation is essential. AB - Thank you for publishing the Department of Health's guidance on Gulf War casualty treatment ('Clinical guidance for nurses', Nursing Standard January 23). PMID- 27667247 TI - Sinking heart. AB - My heart sank when I read Barbara Vaughan's Soapbox, 'Mixing and matching' (Nursing Standard January23). PMID- 27667250 TI - Clues across. AB - 4. Broad, flat spoon (7) 8. Pole's headgear? (3-3) 9. Element from another planet? (7) 10. Fate is encountered by Rex first (6) 12. Cotton (4) 12. Cotton (4) 12. Cotton (4) 13. Forbidden fruit stuck in one's throat (5,5) 17. It is not unusual to have this infection (6,4) 18. One in the role of champion (4) 19. In a frenzy mentioned a protein (6) 21. Supernatural (7) 22. Lay blame on (6) 23. Next Month (7). PMID- 27667249 TI - Helping student nurses. AB - In 'Student nurses and counselling services' (Nursing Standard January 9) Margaret Doust presented an extremely interesting. PMID- 27667251 TI - Pillory to post code. AB - As Superintendent Radiographers at the hospital referred to in 'Don't forget your post code' (Nursing Standard Letters, January 23), we feel that Ms Nash has failed to check her facts. PMID- 27667252 TI - The same old threat. AB - Once again, the 'threat' of health care support workers has been aired in Barbara Vaughan's Soapbox, 'Mixing and matching' (Nursing Standard, January 23). PMID- 27667254 TI - It's competition time. AB - This hopefully should be the last edition of Tradimus we shall ever publish. PMID- 27667253 TI - Oops. AB - We would like to point out that the institution referred to in 'Lucky us' (Letters, Nursing Standard January 30), is in fact Bournemouth Polytechnic and not Bristol, as published. We apologise for the error. PMID- 27667256 TI - Smile please. AB - I have been a nursing student in Scotland for two years and would like to take this opportunity to voice my impressions on the behaviour of my nursing officers. PMID- 27667255 TI - A force for change. AB - Jane Salvage's reward for speaking out during her student days was to be marched off her ward to a confrontation meeting with her Director of Nurse Education, who demanded that she never publish her opinions again without approval. PMID- 27667257 TI - In and out of nursing. AB - When I was asked to write about my reasons for choosing nursing as a career, and why I subsequently left the profession after only eight months of training, I don't think I had fully resolved the issue in my own mind. But preparing to write this piece has proved cathartic. PMID- 27667258 TI - Patti Sheeks. AB - A smarty boots, eh? Whatever did you come into nursing with a degree for? Why didn't you go into medicine? PMID- 27667259 TI - Large area Germanium Tin nanometer optical film coatings on highly flexible aluminum substrates. AB - Germanium Tin (GeSn) films have drawn great interest for their visible and near infrared optoelectronics properties. Here, we demonstrate large area Germanium Tin nanometer thin films grown on highly flexible aluminum foil substrates using low-temperature molecular beam epitaxy (MBE). Ultra-thin (10-180 nm) GeSn film coated aluminum foils display a wide color spectra with an absorption wavelength ranging from 400-1800 nm due to its strong optical interference effect. The light absorption ratio for nanometer GeSn/Al foil heterostructures can be enhanced up to 85%. Moreover, the structure exhibits excellent mechanical flexibility and can be cut or bent into many shapes, which facilitates a wide range of flexible photonics. Micro-Raman studies reveal a large tensile strain change with GeSn thickness, which arises from lattice deformations. In particular, nano-sized Sn enriched GeSn dots appeared in the GeSn coatings that had a thickness greater than 50 nm, which induced an additional light absorption depression around 13.89 MUm wavelength. These findings are promising for practical flexible photovoltaic and photodetector applications ranging from the visible to near-infrared wavelengths. PMID- 27667260 TI - Effector Diversification Contributes to Xanthomonas oryzae pv. oryzae Phenotypic Adaptation in a Semi-Isolated Environment. AB - Understanding the processes that shaped contemporary pathogen populations in agricultural landscapes is quite important to define appropriate management strategies and to support crop improvement efforts. Here, we took advantage of an historical record to examine the adaptation pathway of the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo) in a semi-isolated environment represented in the Philippine archipelago. By comparing genomes of key Xoo groups we showed that modern populations derived from three Asian lineages. We also showed that diversification of virulence factors occurred within each lineage, most likely driven by host adaptation, and it was essential to shape contemporary pathogen races. This finding is particularly important because it expands our understanding of pathogen adaptation to modern agriculture. PMID- 27667261 TI - Contraception for the perimenopausal woman. AB - Perimenopause, or the menopause transition, is a time in a woman's life that bridges her reproductive years through to the non-surgical cessation of ovulation, or menopause. For many women this time is one of changes: changes in gynecological issues, onset of symptoms not experienced in her youth and increasing risks for adverse medical conditions. Despite the clear changes that occur for many women during this time, one critical issue is frequently ignored, namely, that, until the onset of menopause, she is exposed to pregnancy if sexually active, and pregnancy for older reproductive women is fraught with considerable increases in morbidity and mortality compared to younger women. This paper will present a review of the reproductive issues of the perimenopause and interventions geared to preventing pregnancy and relieving menopause-related symptoms. As counseling remains a critical aspect in empowering women to make informed choices about their health care, this paper will present current evidence that will help clinicians provide accurate reproductive counseling to women in the menopause transition. PMID- 27667262 TI - Controllably releasing long-lived quantum memory for photonic polarization qubit into multiple spatially-separate photonic channels. AB - We report an experiment in which long-lived quantum memories for photonic polarization qubits (PPQs) are controllably released into any one of multiple spatially-separate channels. The PPQs are implemented with an arbitrarily polarized coherent signal light pulses at the single-photon level and are stored in cold atoms by means of electromagnetic-induced-transparency scheme. Reading laser pulses propagating along the direction at a small angle relative to quantum axis are applied to release the stored PPQs into an output channel. By changing the propagating directions of the read laser beam, we controllably release the retrieved PPQs into 7 different photonic output channels, respectively. At a storage time of deltat = 5 MUs, the least quantum-process fidelity in 7 different output channels is ~89%. At one of the output channels, the measured maximum quantum-process fidelity for the PPQs is 94.2% at storage time of deltat = 0.85 ms. At storage time of 6 ms, the quantum-process fidelity is still beyond the bound of 78% to violate the Bell's inequality. The demonstrated controllable release of the stored PPQs may extend the capabilities of the quantum information storage technique. PMID- 27667263 TI - The impact of an implementation intention to improve mealtimes and reduce jet lag in long-haul cabin crew. AB - OBJECTIVE: Jet lag is common place amongst long-haul cabin crew. Timed food has been shown to reset the circadian rhythm in rodents. Implementation intentions have been used to change eating behaviour. Mealtimes could therefore be used as a countermeasure to reduce jet lag and improve alertness in long-haul cabin crew through forming an implementation intention to improve the regularity of meals on days off. DESIGN: Sixty long-haul crew took part in a randomised controlled trial, with two conditions: forming an implementation intention to eat regular meals on days off vs. no implementation intention. Pre-intervention measurements were taken at baseline (before a long-haul trip) and post-intervention measures were taken on the first and second days off post-trip. MAIN OUTCOME MEASURES: Subjective jet lag (unidimensional and multidimensional) and objective alertness (Psychomotor Vigilance Task (PVT)). RESULTS: Mixed ANOVA showed a significant condition x time interaction for unidimensional jet lag but not for multidimensional jet lag and objective alertness. In particular, the formation of an implementation intention to alter mealtimes resulted in a reduction of unidimensional jet lag. CONCLUSION: Implementation intentions can be used to alleviate jet lag in long-haul crew through promoting a change in mealtimes. PMID- 27667264 TI - Phytol has antibacterial property by inducing oxidative stress response in Pseudomonas aeruginosa. AB - Phytol, isolated from Aster yomena, is widely distributed as a constituent of chlorophyll. In the present study, we confirmed the antibacterial activity of phytol and its mechanism inducing oxidative cell death in Pseudomonas aeruginosa. In phytol-treated cells, elevated level of intracellular reactive oxygen species (ROS) and transient NADH depletion were observed. These results demonstrated that phytol induced ROS accumulation and that the electron transport chain was involved in increase of ROS. Due to this ROS generation, the imbalance developed between intracellular ROS and the antioxidant defense system, leading to decrease of reduced glutathione (GSH). Moreover, severe DNA damage was shown after treatment with phytol. DNA electrophoresis and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were conducted with pretreatment with the antioxidant N-acetylcysteine (NAC) to evaluate the cause of DNA damage. In NAC-pretreated cells, alleviated damage was confirmed and it supports that phytol induces oxidative stress-mediated DNA damage. In conclusion, phytol exerts the antibacterial property via inducing oxidative stress response in P. aeruginosa. PMID- 27667265 TI - Quercetin-containing self-assemble proliposome preparation and evaluation. AB - The purpose of this study was to develop a liquid self-assemble proliposome for quercetin oral delivery. This liquid proliposome was prepared by dissolving phospholipids, surfactants and drug in ethanol. There was only one step in the preparation process of this liquid self-assemble proliposome and no special devices were required. The mechanism about proliposome transformation was discussed. Quercetin proliposomes with different cremorphor RH40 concentrations (0%, 20%, 23%, 26%, 30%) were prepared. The particle size and polydispersity index decreased as cremorphor RH40 concentration increased. Meantime, the drug entrapped efficiency decreased slightly with an increase in cremorphor RH40 concentration. The in vitro drug release showed prolonged drug release in case of proliposome and the release of quercetin was slower when cremorphor RH40 concentration was higher. The absorption of quercetin and its in vivo bioavailability were significantly improved by proliposome, which was evidenced by the in situ intestinal absorption and pharmacokinetic study. Besides, the obtained quercetin proliposome was with good stability when stored at room temperature. In conclusion, quercetin liquid self-assemble proliposome was successfully prepared. It could transform into liposomal vesicle with satisfied particle size and polydispersity index instantly when cremorphor RH40 was added. Cremorphor RH40 concentration in the formulation should below 26% to get higher drug entrapped efficiency (>90%) and less irritation. The drug release was affected by the cremorphor RH40 concentration and the required drug release could be obtained by adjusting cremorphor RH40 content. The enhanced bioavailability showed liquid self-assemble proliposome could be a promising vehicle for the oral delivery of quercetin. PMID- 27667266 TI - Upregulation of INS-IGF2 read-through expression and identification of a novel INS-IGF2 splice variant in insulinomas. AB - Fusion transcripts arising from the combination of exons residing on neighboring genes on the same chromosome may give rise to chimeric or novel proteins. Such read-through transcripts have been detected in different cancers where they may be of pathogenetic interest. In this study, we describe for the first time the expression of a read-through transcript in insulinomas, a functioning neuroendocrine pancreatic neoplasm. The read-through transcript INS-IGF2, composed of exons from the two genes proinsulin precursor (INS) and insulin-like growth factor 2 (IGF2), both mapping to chromosomal subband 11p15.5, was highly expressed in the two insulinomas analyzed. More precisely, version 2 of the INS IGF2 transcript was expressed, indicating possible expression of the chimeric INS IGF2 protein. We further identified a novel splice variant of the INS-IGF2 read through transcript in one of the insulinomas, composed of exon 1 of INS3 and exons of IGF2. In the same tumor, we found high expression of INS3 and the presence of the A allele at SNP rs689. SNP rs689 has been previously described to regulate splicing of the INS transcript, indicating that this regulatory mechanism also affects splicing of INS-IGF2. The identification of the INS-IGF2 read-through transcript specifically in tumor tissue but not in normal pancreatic tissue suggests that high expression of INS-IGF2 could be neoplasia-specific. These results may have potential clinical applications given that the read through transcript could be used as a biomarker in insulinoma patients. PMID- 27667268 TI - It Takes Two to Tango: When and Where Dual Nutrient (N & P) Reductions Are Needed to Protect Lakes and Downstream Ecosystems. AB - Preventing harmful algal blooms (HABs) is needed to protect lakes and downstream ecosystems. Traditionally, reducing phosphorus (P) inputs was the prescribed solution for lakes, based on the assumption that P universally limits HAB formation. Reduction of P inputs has decreased HABs in many lakes, but was not successful in others. Thus, the "P-only" paradigm is overgeneralized. Whole-lake experiments indicate that HABs are often stimulated more by combined P and nitrogen (N) enrichment rather than N or P alone, indicating that the dynamics of both nutrients are important for HAB control. The changing paradigm from P-only to consideration of dual nutrient control is supported by studies indicating that (1) biological N fixation cannot always meet lake ecosystem N needs, and (2) that anthropogenic N and P loading has increased dramatically in recent decades. Sediment P accumulation supports long-term internal loading, while N may escape via denitrification, leading to perpetual N deficits. Hence, controlling both N and P inputs will help control HABs in some lakes and also reduce N export to downstream N-sensitive ecosystems. Managers should consider whether balanced control of N and P will most effectively reduce HABs along the freshwater-marine continuum. PMID- 27667267 TI - The structural basis for CD36 binding by the malaria parasite. AB - CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum, tethering parasite infected erythrocytes to endothelial receptors. This prevents their destruction by splenic clearance and allows increased parasitaemia. Here we describe the structure of CD36 in complex with long chain fatty acids and a CD36-binding PfEMP1 protein domain. A conserved hydrophobic pocket allows the hugely diverse PfEMP1 protein family to bind to a conserved phenylalanine residue at the membrane distal tip of CD36. This phenylalanine is also required for CD36 to interact with lipoprotein particles. By targeting a site on CD36 that is required for its physiological function, PfEMP1 proteins maintain the ability to tether to the endothelium and avoid splenic clearance. PMID- 27667269 TI - [Target blood pressure in hypertensive patients complicating with frailty syndrome]. PMID- 27667270 TI - [Comparison on metabolic disorders and uric acid levels between patients with primary aldosteronism and essential hypertension]. AB - Objective: To compare the incidence of metabolic disorders and uric acid (UA) levels between patients with primary aldosteronism (PA) and essential hypertension (EH), and to explore factors associated with UA levels in these patients. Methods: A total of 117 PA and 117 EH patients individually matched by sex, age, blood pressure and duration of hypertension were recruited from in hospital patients who were hospitalized in our department because of suspicion of secondary hypertension from January 2008 to December 2014. Clinical data including metabolic disorders and UA levels were analyzed. Results: (1) Body mass index (BMI), waist circumference, plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA) were significantly higher in EH than in PA group (all P<0.05). Prevalence of diabetes mellitus or impaired glucose tolerance (DM+ IGT) was significantly higher in EH than in PA group (41.9% (49/117) vs. 17.1% (20/117), P<0.01). The prevalence of metabolic syndrome (MS) was also significantly higher in EH than in PA group (51.3% (60/117) vs. 24.8% (29/117), P<0.01). (2) EH patients had higher homeostasis model assessment for insulin resistance (HOMA-IR) and lower insulin sensitivity index composite (ISI comp) than PA patients, but basic insulin secretion index (HOMA-beta) and modified beta cell function index (MBCI) were significantly lower in PA than in EH group (P<0.05). (3) With regard to target organs damages, PA patients revealed higher 24-hour urinary protein, urinary albumin excretion rate (UAER), urinary IgG, urinary alpha-1 microglobulin, left ventricular mass index and lower urine specific gravity than EH patients (all P<0.05). There was no significant difference in estimated glomerular filtration rate (eGFR) between two groups (P=0.103). (4) UA level was significantly lower in PA group than in EH group ((314.00+/-89.52) MUmol/L vs. (379.16+/-101.25) MUmol/L, P<0.01). Higher plasma aldosterone concentration and lower plasma renin activity were associated with lower UA level in PA group. Conclusions: Compared with sex, age and hypertension duration matched EH patients, PA patients revealed lower UA level and less severe abnormalities of glucose and lipid metabolism, but are associated with severer renal and cardiac damages. The reduced UA level in PA patients is possibly due to the high plasma aldosterone concentration and low plasma renin activity. PMID- 27667271 TI - [Association between ambulatory arterial stiffness index with left ventricular mass index in the elderly hypertensive patients]. AB - Objective: To investigate the relationship between ambulatory arterial stiffness index (AASI) and left ventricular mass index (LVMI) in the elderly hypertensive patients. Methods: This study population consisted of 332 elderly hypertensive patients, who hospitalized in our department from January 2012 to December 2014.AASI was calculated from 24 h ambulatory BP monitoring recordings and LVMI from echocardiography examination.According to the median value of AASI, patients were divided to less than the AASI median group (low AASI group) and equal to or above the AASI median group (high AASI group). Differences between two groups were evaluated using the Student's t-test and Chi-square test.Univariate association was assessed by the Pearson correlation analyses.Multivariate linear regression models were performed to analyze the correlation between AASI and LVMI. Results: LVMI was significantly higher in high AASI group compared with low AASI group ( (115.91+/-21.36) g/m2 vs.(104.11+/-17.24) g/m2,P=0.008). Pearson correlation analyses showed that AASI and 24 h pulse pressure were positively correlated to LVMI (r=0.332, P<0.001; r=0.169, P=0.002). In multivariate linear regression model, AASI(beta=44.48, P<0.001), LDL-C(beta=-5.97, P<0.001) and UA (beta=0.02, P=0.045)showed significant association with LVMI. Conclusion: AASI independently associated with LVMI, and AASI might be one predictor of left ventricular hypertrophy in hospitalized elderly hypertensive patients. PMID- 27667272 TI - [Epidemiological study of hypertension in Dongxiang population of Dongxiang county in Gansu province]. AB - Objective: To investigate the prevalence, awareness, treatment and control rate of hypertension among Dongxiang population of Dongxiang county in Gansu province, and analyze risk factors of hypertension in this population. Methods: A total of 1 879 Dongxiang residents of Dongxiang county in Gansu province aged 18 years and over were selected in one town and eight villages by random cluster method from April to June in 2014. All subjects were interviewed and physical examination including blood pressure measurement was performed. Multivariate logistic regression analysis was used to analyze the risk factors of hypertension. Results: Prevalence of hypertension in this population was 21.4%(402/1 879). Prevalence of hypertension increased with aging and was 7.9%(35/441) in 18-39 years old people, and 20.2%(151/749)in 40-59 years old people, and 31.3%(216/689)in >=60 years old people (P<0.01). There were no gender (male vs. female) difference in prevalence of hypertension in 18-39 years old group (8.0%(20/249)vs. 7.8%(15/192), P>0.05) and 40-59 years old group (19.8%(78/393) vs. 20.5%(73/356), P>0.05), while the prevalence of hypertension was significantly higher in male than in female(34.2%(123/360) vs. 28.3%(93/329), P<0.01)in >=60 years old group. Prevalence of hypertension was also significantly higher in rural area residents than in county town residents (23.4%(255/1 090) vs.18.6%(147/789), P<0.01). The rates of awareness, treatment and control of hypertension in this population were 24.4%(98/402), 14.7%(59/402) and 5.0%(20/402), respectively. Rates of awareness (22.7%(58/255)vs. 27.2%(40/147), P<0.01), treatment(13.3%(34/255)vs. 17.0%(25/147), P<0.05) and control(3.9%(10/255)vs. 6.8%(10/147), P<0.05) were significantly lower in rural area residents than in county residents. Multivariate logistic regression analysis showed that age, family history of hypertension, high body mass index, less physical activity and more static state were risk factors of hypertension in this population(P<0.05 or 0.01). Conclusions: Prevalence of hypertension is high and awareness, treatment and control rates of hypertension are low in adult residents of Dongxiang county in Gansu province. Hypertension prevention focusing on risk factors control and treatment strategies should be enhanced in this population. PMID- 27667275 TI - [Long-term outcome and related predictors of alcohol septal ablation for patients with hypertrophic obstructive cardiomyopathy]. AB - Objective: To observe the long-term prognosis and related outcome predictors for hypertrophic obstructive cadiomyopathy (HOCM) patients underwent alcohol septal ablation (ASA). Methods: A total of 227 consecutive patients(age: (47.8+/-11.7) years) treated by ASA from September 2005 to December 2013 in our hospital were included and followed-up for 4.42 years(range: ( 1.17-9.93) years). Follow up rate is 97.4%(221/227). General information, medical history, data of ASA and complications during hospitalization were obtained through access to medical records of patients. The patients were followed up by telephone or outpatient visit. Results: During hospitalization period, one patient died due to retroperitoneal hemorrhage, two ventricular fibrillation events and two sustained ventricular tachycardia events occurred and all patients were successfully recovered after electrical cardioversion (defibrillation). Four cardiac tamponade events occurred, 35.7% (81/227) patients experienced temporary three degree atrioventricular block. Five delayed three degree atrioventricular block evens occurred. During follow up, the percent of NYHA III/IVclass was significantly reduced (10.1%(23/227)vs. 74.9%(170/227), P=0.000). The incidence of syncope and amaurosis fugax was also reduced(2.6% (6/227) vs. 39.2% (89/227), P=0.035). A total of six patients died (4 cardiac death), one patient complicating atrial fibrillation died of cerebral embolism, one patient died of rectal cancer. One cerebral hemorrhage occurred. Six patients developed-new onset atrial fibrillation. One patient received permanent pacemaker implantation. Eight patients received surgical myocardial resection. Three patients underwent repeated ASA. Survival free of all-cause mortality at 1, 5, 9 year was 100%, 96%, 96%, respectively. Survival free of cardiac death and NYHA III/IVclass at 1, 5, 9 year was 100%, 86%, 70%, respectively. Cox-regression analysis showed that residual left ventricular outflow tract gradient after ablation(HR=1.027, 95%CI 1.006-1.048, P=0.010), less volume of injected ethanol(HR=0.596, 95%CI 0.398 0.892, P=0.012), presence of temporary complete atrioventricular block (HR=0.332, 95%CI 0.124-0.886, P=0.028)were independent predictors of cardiac death and NYHA III/IV. Conclusion: Our study results suggest that ASA could significantly improve symptoms and outcome in patients with HOCM. Residual left ventricular outflow tract gradient after ablation, less volume of injected ethanol, presence of temporary complete atrioventricular block during ASA are independent predictors of cardiac death and NYHA III/IV. PMID- 27667274 TI - [Efficacy of thrombolytic therapy using reteplase in cases with acute ST-segment elevation myocardial infarction: results from a multicenter clinical trial]. AB - Objective: To evaluate the efficacy and safety of intravenous thrombolytic therapy using reteplase in patients with acute ST-segment elevation myocardial infarction (STEMI). Method: A total of 73 hospitals from Henan province took part in this clinical trials during October 2012 to October 2014, 1 226 cases (1 014 male (82.7%), mean age 59.0 (51.0, 66.0) years) with acute STEMI received reteplase as thrombolytic agent.Reperfusion rate was judged according to the clinical symptoms, electrocardiogram, myocardial enzymes and heart rhythm, and the rate of cardiovascular events and bleeding events during hospitalization was also observed.Bleeding events were evaluated with global utilization of streptokinase and tissues plasminogen activator for occluded coronary arteries (GUSTO) criteria.Subgroup analysis was performed to compare the effects of various thrombolysis timing (time from onset to thrombolysis<=6 h or 6-12 h) on reperfusion rate, cardiovascular events and bleeding events rate. Results: The reperfusion rate was 89.3% (1 089/1 219) at 120 minutes after the thrombolysis, average recanalization time was (59.96+/-26.86) minutes.The reperfusion rate of <=6 h thrombolysis group was significantly higher than in 6-12 hours group (90.3% (988/1094) vs. 80.8% (101/125), P=0.001), while in-hospital mortality (2.6%(28/1 094) and 0.8% (1/125), P=0.352) and rate of bleeding (5.9%(64/1 094) and 5.6%(7/125), P=0.910) were similar between the two groups. The total in-hospital mortality after thrombolysis was 2.4% (29/1219), which was significantly higher in failed recanalization group than in recanalization group (10.8%(14/130) vs. 1.4%(15/1089), P< 0.001). The total rate of bleeding after thrombolysis was 5.8% (71/1219), there were 3 severe bleeding cases according to GUSTO classification (0.2%), all of them were cerebral hemorrhage, and 2 out of 3 cases died. Conclusions: Reteplase use is related to high recanalization rate and low cardiovascular events and bleeding rate and our results thus show that reteplase is a safe and effective thrombolytic agent for STEMI patients. PMID- 27667273 TI - [Tetrahydrobiopterin improves left ventricular diastolic function possibly through upregulating phosphorylated protein kinase B expression in hypertensive mice induced by deoxycorticosterone acetate]. AB - Objective: To investigate whether tetrahydrobiopterin (BH4) could improve left ventricular diastolic function through phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) signaling pathway in hypertensive mice. Methods: Ten-week-old male C57BL/6 mice were used to establish the deoxycorticosterone acetate (DOCA)-salt hypertensive model, age matched Sham mice serve as the controls. Mice were divided into four groups: Sham(n=20), Sham+ BH4 (n=20), DOCA (n=22), and DOCA+ BH4 (n=22). On the 14 days after surgery, mice in Sham+ BH4 and DOCA+ BH4 groups received BH4 (0.1 ml/10 g) supplement for 7 days, while mice in Sham and DOCA groups were given equal volume of normal saline.The blood pressure measurements were performed 7 days later.Hemodynamic and echocardiographic parameters were used to assess left ventricular functions.High performance liquid chromatography (HPLC) analysis was used to measure cardiac biopterins BH4 and BH2.The phosphorylated phospholamban (p-PLB) was detected by immunohistochemical staining. PI3K, Akt and phosphorylated Akt were assayed with Western blot analysis. Results: (1) The systolic and diastolic blood pressure of DOCA group were significantly higher than control group (P<0.05). Compared with DOCA group, the systolic blood pressure was lower in DOCA+ BH4 mice (P=0.027). Diastolic blood pressure was similar between the groups. (2) Compared with Sham group, the left ventricular diastolic function indexes such as mitral annulus velocity (E') and E'/A'ratio were significantly lower, while the E/ E'ratio was significantly higher(P<0.05)in DOCA mice. The E/ E'ratio of DOCA+ BH4 group was significantly lower than that of DOCA group (P<0.05). Compared with Sham group, the left ventricular end-diastolic pressure (LVEDP), left ventricular end-diastolic pressure volumetric coefficient (EDPVR) and left ventricular relaxation time constant Tau index were significantly higher in DOCA mice (P=0.002, 0.011 and 0.016, respectively). The EDPVR and Tau index were significantly lower in DOCA+ BH4 group than in DOCA group (P<0.05). (3) Compared with Sham group, the myocardial contents of BH4 and BH2 were significantly lower in DOCA mice (P<0.05). The BH4 levels and BH4/BH2 ratio were significantly higher in Sham+ BH4 and DOCA+ BH4 groups than in the DOCA group (P<0.05), but the BH2 levels were similar between groups. (4) The cGMP content, SOD activity and NO content in the left ventricular myocardial tissue were significantly lower (P<0.05), while the MDA content was significantly higher in DOCA mice than in Sham mice.The NO content and SOD activity in DOCA+ BH4 groups were significantly higher than in the DOCA group (P<0.05). (5) Compared with DOCA group, the expression of p-PLB was significantly higher in Sham mice and lower in DOCA+ BH4 mice (P<0.05). (6) The expression of PI3K, Akt and p-Akt (Ser473 and Thr308) in DOCA mice were significantly lower than in Sham group (P<0.05). The expression of PI3K, Akt and p-Akt (Ser473) was significantly higher in DOCA+ BH4 group than in DOCA group (P<0.05). p-Akt (Thr308) expression was similar between DOCA + BH4 group and DOCA group (all P>0.05). Conclusion: Our results suggest that BH4 could improve left ventricular diastolic function in hypertensive mice, this effect might be mediated by reducing the oxidative stress in ventricular myocardium through modlating the expression of Akt and PLB phosphorylation. PMID- 27667276 TI - [The effect and factors associated with outcome of extracorporeal membrane oxygenation in refractory cardiogenic shock patients]. AB - Objective: To observe the clinical efficacy and factors associated with outcome of extracorporeal membrane oxygenation (ECMO) in refractory cardiogenic shock patients. Methods: Patients with refractory cardiogenic shock received ECMO treatment in our hospital from May 2013 to November 2015 were retrospectively analyzed. The clinical status before ECMO support, ECMO timing, complications and outcome were observed and analyzed.The hemodynamic data and the amount of vasoactive drugs at 2 hours before ECMO support and at 2, 6, 24 and 48 hours after ECMO support were collected and compared. Results: Ten refractory cardiogenic shock patients were included in this study (5 acute fulminant myocarditis patients, 4 acute myocardial infarction patients, 1 myocardial rupture patient (6 males, 4 females, age ranged 12 to 56 years). Before ECMO, the mean left ventricular ejection fraction (LVEF) was (31.4+/-10.2)%, the mean score of APACHE II was 26.6+/-10.8. Eight patients developed cardiac arrests and the duration of CPR ranged from 10 to 300 minutes and three patients received IABP. CVP decreased, BP increased, HR decreased, ScVO2 increased, dose of dobutamine decreased at 2 hours after ECMO support. After ECMO support for 6 hours, lactate decreased, dose of norepinephrine decreased. After ECMO support for 24 and 48 hours, hemodynamics became stable and shock was significantly improved. Complication including infection of limb and catheterization site occurred in 3 patients, femoral arterial thrombosis occurred in 2 patients, critical limb ischemia occurred in 2 patients, hemorrhage at the catheterization site occurred in 2 patients. The duration of ECMO ranged from 2 to 220 hours. Nine patients could be weaned off ECMO support and 6 patients survived to hospital discharge. Two patients died due to too late ECMO support, the other two patients died due to severe complication of limb. Conclusions: ECMO can rapidly improve hemodynamic stability of patients with cardiogenic shock. Accurate assessing the timing of ECMO support and decreasing complication of limb play a critical role on improving outcome in refractory cardiogenic shock patients. PMID- 27667277 TI - [Pedigree survey in a family with hereditary protein S deficiency]. AB - Objective: To observe the clinical feature of familiar hereditary protein S deficiency(HPSD), and to explore the related gene mutations. Methods: A total of seven family members were enrolled in this study and examined during the June to September 2015. Medical histories of the families were analyzed to detect HPSD according to the diagnostic criteria. PROS1 genes of the proband and her family were analyzed. DNA was extracted from peripheral blood. The 15 exons and their intron-exon boundaries of PROS1 were amplified with PCR, and the PCR products were sequenced and analyzed to identify potential mutations. Medical histories from the family members died prior this study were also obtained. Results: Four out of 7 family members of 2 generations were diagnosed as HPSD. The proband suffered from pulmonary embolism, her elder brother suffered from cerebral infarction and her niece suffered from deep vein thrombosis. A missense mutation at the 1063 bp of cDNA(c.1063C>T)was detected in the exon 10 of PROS1, which resulted in arginine 355 to cysteine replacement in the first ball domain of laminin of the protein S(p.R355C). Conclusion: HPSD is an autosomal dominant genetic disease, patients often suffer from recurring vein thrombosis and pulmonary embolism. A missense mutation(c.1063C>T, p. R355C)of PROS1 was discovered in this Chinese family with HPSD, thus, this mutation might be the genetic basis responsible for these family members with HPSD . PMID- 27667278 TI - [Effect of Notch1, 2, 3 genes silencing on Notch and nuclear factor-kappaB signaling pathway of macrophages derived from patients with coronary artery disease]. AB - Objective: To investigate the effects of Notch1, 2, 3 genes silencing by siRNA on Notch signaling pathway (Delta-like 4(DLL4), Jagged 1(JAG1)) and nuclear factor kappaB (NF-kappaB) signaling pathway (IkappaBalpha, P52) of macrophages derived from patients with coronary artery disease (CAD), thus to explore the potential genetic treatment perspectives for CAD. Methods: Peripheral blood mononuclear cells of CAD patients were isolated by density gradient centrifugation and transformed by phorbol-12-myristate-13-acetate (PMA) to macrophages. Macrophages were then transfected with Notch1-small interference RNA (siRNA, Notch1-siRNA group), Notch2-siRNA (Notch2-siRNA group), Notch3-siRNA (Notch3-siRNA group), negative control siRNA (NC group) and none siRNA (control group) respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were applied to assess the mRNA and protein expression levels of DLL4, JAG1, IkappaBalpha and p52, respectively. Electrophoretic mobility shift assay (EMSA) was used to observe the NF-kappaB DNA binding activity. Subcellular distributions of NF-kappaB/p52 were detected through immunofluorescence. Results: (1) The mRNA and protein expressions of DLL4, JAG1 and p52 in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group were significantly downregulated, while the mRNA and protein expression of IkappaBalpha was significantly upregulated compared with NC group and control group(P<0.05 or 0.01). The mRNA and protein expressions of DLL4, JAG1 and p52 in Notch1-siRNA group were significantly downregulated, while the mRNA and protein expression of IkappaBalpha was significantly upregulated compared with Notch2-siRNA group and Notch3-siRNA group(P<0.05 or 0.01). The mRNA and protein expressions of DLL4, JAG1, IkappaBalpha and p52 were similar between NC group and control group (all P>0.05). (2) The binding activity of NF-kappaB DNA was significantly lower in Notch1-siRNA group (613+/-57), Notch2-siRNA group (1 169+/-85) and Notch3-siRNA group (1 454+/-90) compared with control group (2 643+/-115) and NC group (2 407+/-100) (all P<0.01), which was also significantly lower in Notch1-siRNA group compared to Notch2-siRNA group and Notch3-siRNA group (P<0.01); was significantly lower in Notch2-siRNA group compared with Notch3-siRNA group (P<0.01) and was similar between control group and NC group (P>0.05). (3) The fluorescence intensity of NF-kappaB/p52 was significantly lower both in the nucleus and cytoplasm in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group compared with NC group and control group (all P<0.01), and the decrease was more obviously in the nucleus than in cytoplasm in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group (P<0.05 or 0.01). The fluorescence intensity of NF kappaB/p52 was similar between control group and NC group (P>0.05). Conclusion: There is a positive regulation between Notch and NF-kappaB pathway in macrophages derived from CAD patients, the regulation power on NF-kappaB signaling pathway of Notch1 is stronger than that of Notch2 and Notch 3. PMID- 27667279 TI - [Effects of ligustilide on the extracellular recombinant human heat shock protein 60 induced inflammatory reactions in the THP-1 cells and the related mechanisms]. AB - Objective: To investigate the effects of ligustilide(LIG) on extracellular recombinant human heat shock protein 60 (HSP60) induced inflammatory reactions in the THP-1 cells and the related mechanisms. Methods: THP-1 cells were differentiated to macrophages by incubation with phorbol-12-myristate-13-acetate (PMA). The immunofluorescence method was used to screen the optimum transfection concentration of MyD88 siRNA.The macrophages were divided into six groups(n=3), including blank control(siRNA transfection reagent), model(siRNA transfection reagent+ HSP60 10 mg/L), negative control(MyD88 negative control+ HSP60 10 mg/L), LIG group(siRNA transfection reagent+ HSP60 10 mg/L+ LIG 20 mg/L), RNA interfering(RNAi) group(MyD88 siRNA+ HSP60 10 mg/L) and RNAi+ LIG group(MyD88 siRNA+ HSP60 10 mg/L+ LIG 20 mg/L). The protein expression level of MyD88 and phospho-nuclear factor-kappaB(p-NF-kappaB) in macrophages and the level of tumor necrosis factor-alpha(TNF-alpha) and interleukin-6(IL-6) in the culture supernatant were assessed by Western blot analyses or ELISA, respectively. Results: (1)The protein expression levels of MyD88 (1.196+/-0.125 vs. 0.341+/ 0.063, P<0.01) and p-NF-kappaB(0.817+/-0.034 vs. 0.312+/-0.046, P<0.01) were significantly higher in the model group than those in the blank control group.The protein expression levels of MyD88(0.554+/-0.043) and p-NF-kappaB(0.538+/-0.063) in the RNAi group were significantly lower than those in the model group (all P<0.01) but significantly higher than those in the blank control group (all P<0.05). The protein expression levels of MyD88(0.694+/-0.087, P<0.05) and p-NF kappaB(0.669+/-0.043, P<0.01)in the LIG group were markedly lower than those in the model group, but higher than those in the RNAi group (P<0.05) and the blank control group (P<0.01). The protein expression levels of MyD88(0.409+/-0.069) and p-NF-kappaB(0.395+/-0.046) in the RNAi+ LIG group were significantly lower than in the model group (all P<0.01) and in the LIG group(P<0.05 or 0.01), and were similar to the blank control group(P>0.05). The expression level of p-NF-kappaB in the RNAi+ LIG group was significantly lower than in the RNAi group (P<0.05). (2) The contents of TNF-alpha((312.24+/-28.69) ng/L vs. (5.99+/-1.03) ng/L, P<0.01) and IL-6((233.45+/-57.77) ng/L vs. (2.25+/-0.67) ng/L, P<0.01) were significantly higher in the model group than in the blank control group. The contents of TNF-alpha((235.66+/-25.12) ng/L) and IL-6((131.59+/-13.99) ng/L) were significantly lower in the RNAi group than in the model group (P<0.01). The contents of TNF-alpha((258.13+/-44.80) ng/L) and IL-6((175.92+/-28.27) ng/L) were also significantly lower in the LIG group than in the model group(P<0.05) while the content of IL-6 was significantly higher in the LIG group than in the RNAi group(P<0.01). The contents of TNF-alpha((88.57+/-16.10) ng/L) and IL-6((59.99+/ 10.31) ng/L) were significantly lower in the RNAi+ LIG group than those in the model group, the RNAi group and the LIG group(P<0.05 or 0.01). Conclusions: The MyD88/NF-kappaB signaling pathway is one of the key signaling pathways of human HSP60 induced inflammation in THP-1 cells. Ligustilide could exhibit the anti inflammatory effect probably by inhibiting the MyD88/NF-kappaB signaling pathway. PMID- 27667280 TI - [Lipid profile comparison between pre- and post-menopausal women]. AB - Objective: To compare serum lipid values in premenopausal and postmenopausal women and to evaluate the relationship between menopause and lipid profiles. Methods: From January 2012 to December 2014, a total of 4 131 women aged between 40 and 59 years old were recruited as subjects in the Checkup Department of Beijing Tongren Hospital, and were grouped as pre-menopausal group (3 094 subjects) and post-menopausal group(1 037 subjects). Data including body mass index(BMI), waist circumference, hip circumference, waist-hip circumference ratio, serum total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), non-high-density lipoprotein cholesterol(non-HDL-C), TC/HDL-C ratio, fast plasma glucose, serum uric acid, blood pressure and degree of fatty liver were compared between the two groups. Multivariate logistic regression analysis was applied to analyze the relationship between menopause and dyslipidemia. Results: The overall prevalence rate of dyslipidemia was 35.7%(1 475/4 131) in this cohort, and the prevalence rate of dyslipidemia in post-menopausal women group was significantly higher than in pre-menopausal women group (69.7%(723/1 037)vs. 24.3%(752/3 094), P<0.01). TC ((5.74+/-0.91)mmol/L vs.(4.65+/-0.61)mmol/L, P<0.01), TG((1.79+/-0.95)mmol/L vs. (0.89+/-0.32)mmol/L, P<0.01), LDL-C ((3.76+/-0.86)mmol/L vs. (2.87+/-0.57)mmol/L, P<0.01), non-HDL-C((4.27+/-0.80)mmol/L vs. (3.10+/-0.60)mmol/L, P<0.01), and TC/HDL-C ratio(4.15+/-1.04 vs. 3.13+/-0.72, P<0.01)were all significantly higher in post-menopausal subjects than in pre-menopausal subjects. HDL-C level was significantly lower in post-menopausal subjects than in pre-menopausal subjects((1.47+/-0.43)mmol/L vs. (1.54+/-0.33)mmol/L, P<0.01). Logistic regression analysis showed that after adjusting age, BMI, waist circumference, waist-hip circumference ratio, blood pressure, fast plasma glucose, serum uric acid and fatty liver, menopause was independently associated with dyslipidemia (OR=6.65, 95%CI 5.22-8.48, P<0.01). Factors such as BMI grade (normal body weight: OR=2.19, 95%CI 1.31-3.67, P<0.01; overweight: OR=3.41, 95%CI 2.00-5.83, P<0.01; obesity: OR=3.84, 95%CI 2.05-7.18, P<0.01), waist-hip circumference ratio abnormality (OR=1.68, 95%CI 1.44-1.97, P<0.01) and the degree of fatty liver (mild: OR=1.84, 95%CI 1.54-2.20, P<0.01; moderate: OR=1.67, 95%CI 1.25-2.23, P<0.01; severe: OR=5.23, 95%CI 1.78-15.35, P<0.01) were also associated with dyslipidemia in this cohort. Conclusions: The prevalence of dyslipidemia is higher in post-menopausal women than in pre-menopausal women, and the values of TC, TG, LDL-C, non-HDL-C, TC/HDL-C ratio of postmenopausal women are significantly higher than those of premenopausal women. Menopause is associated with dyslipidemia in this cohort. PMID- 27667281 TI - [A case of Takayasu Arteritis with sudden cardiac arrest as the first manifestation]. PMID- 27667283 TI - [A case of left atrial non-Hodgkin lymphoma misdiagnosed as thrombus]. PMID- 27667282 TI - [A case of left atrial cavernous hemangioma misdiagnosed as myxoma]. PMID- 27667284 TI - [A case of intravenous extraction of implantable cardioverter defibrillator lead with laser sheath]. PMID- 27667285 TI - [A case of late endocarditis of Amplatzer atrial septal occluder device]. PMID- 27667286 TI - [Association between abnormal glucose metabolism and pulmonary vasculature remodeling and progress of therapeutic drugs targeting the glucose metabolism for pulmonary hypertension]. PMID- 27667287 TI - [Research progress on modifying factors of pulmonary arterial hypertension]. PMID- 27667288 TI - [Research update on cytoskeletal proteins mediated pathomechanisms in primary cardiomyopathies]. PMID- 27667289 TI - Benchmarking Electron Densities and Electrostatic Potentials of Proteins from the Three-Partition Frozen Density Embedding Method. AB - The fragment-based Three-Partition Frozen Density Embedding (3-FDE) approach [ Jacob, C. R.; Visscher, L. J. Chem. Phys. 2008 , 128 , 155102 ] is used to generate protein densities and electrostatic potentials, which are critically assessed in comparison to supermolecular Kohn-Sham Density Functional Theory (DFT) results obtained with sophisticated exchange-correlation functionals. The influence of several parameters and user choices is explored with respect to accuracy and reliability. In addition, a recently implemented combination of the 3-FDE scheme with hybrid functionals is applied in production calculations for the first time. We demonstrate that the 3-FDE method not only closely reproduces results from corresponding supermolecular calculations for routine situations (peptides/proteins in solution) but can even surpass conventional Kohn-Sham DFT in accuracy for difficult cases, such as zwitterionic structures in vacuo. This is due to the fact that the fragmentation inherently limits the overdelocalization caused by the self-interaction error in common DFT approximations. The method is thus not only able to reduce the computational effort for the description of large biological entities but also can strongly reduce the artifacts brought about by the SIE. PMID- 27667290 TI - Estimated costs before, during and after the introduction of the emergency laparotomy pathway quality improvement care (ELPQuIC) bundle. AB - Implementation of a quality improvement bundle for peri-operative management of emergency laparotomy (ELPQuIC) improved mortality in a previous study. We used data from one site that participated in that study to examine whether it was associated with the cost of care. We collected data from 396 patients: 144 before, 144 during and 108 after implementation of the bundle. We estimated costs incurred using previously published methodology based on the time the patient spent in hospital, in the operating theatre and in critical care. Duration of stay in hospital and critical care did not differ between time periods, p = 0.14 and p = 0.28, respectively. The costs per patient and per survivor did not differ between the time periods, p = 0.87 and p = 0.17, respectively. Costs were similar for patients aged < 80 years vs. >= 80 years. Implementation of a quality improvement bundle for emergency laparotomy has the capacity to save lives without increasing hospital costs. PMID- 27667291 TI - Mesoscopic Perovskite Light-Emitting Diodes. AB - Solution-processed hybrid bromide perovskite light-emitting-diodes (PLEDs) represent an attractive alternative technology that would allow overcoming the well-known severe efficiency drop in the green spectrum related to conventional LEDs technologies. In this work, we report on the development and characterization of PLEDs fabricated using, for the first time, a mesostructured layout. Stability of PLEDs is a critical issue; remarkably, mesostructured PLEDs devices tested in ambient conditions and without encapsulation showed a lifetime well-above what previously reported with a planar heterojunction layout. Moreover, mesostructured PLEDs measured under full operative conditions showed a remarkably narrow emission spectrum, even lower than what is typically obtained by nitride- or phosphide-based green LEDs. A dynamic analysis has shown fast rise and fall times, demonstrating the suitability of PLEDs for display applications. Combined electrical and advanced structural analyses (Raman, XPS depth profiling, and ToF-SIMS 3D analysis) have been performed to elucidate the degradation mechanism, the results of which are mainly related to the degradation of the hole transporting material (HTM) and to the perovskite-HTM interface. PMID- 27667293 TI - [Close follow-up of oncologic patients with imaging - advantage or disadvantage?] AB - The International Commission on Radiological Protection estimates, that 100 mSv exposure of radiation increases cancer risk by 0.5%. The central hypothesis of the Linear No Threshold model is that low dose ionizing radiation can induce carcinogenesis through the so called "one hit action", that is one or more deoxyribonucleic acid strands can be broken by the hit of only one electron particule. Regardless of the radiation dose, radiation exposure increases cancer risk. In the United States of America, one-third of computed tomographic scans are carried with no clear clinical indication, i.e. non radiating imaging can be applied with equal sensitivity and specificity. Furthermore, computed tomographic scans are repeated unnecessarily. Although technical improvements have reduced the concern of the potential danger of radiation exposure, the cumulative aspects and cancer risk should always be considered. Cancer risk, accompanied by ionizing radiation, should be minimized during the follow up of oncologic patients. It is mandatory, that all diagnostic tools which are not using ionizing radiation should be made widely accessable (eg. whole body diffusion weighted magnetic resonance imaging, positron emission tomography/magnetic resonance imaging). Orv. Hetil., 2016, 157(39), 1538-1545. PMID- 27667294 TI - [Actualities in the management of primary myelofibrosis]. AB - Primary myelofibrosis is one of the Philadelphia negative chronic myeloproliferative neoplasms. It is a rare disease featured by cytopenias and hepatosplenomegaly. Although the etiology of the disease is still unknown, our knowledge about its pathology and prognosis has been improving in the last few years. Furthermore, the JAK2 inhibitor ruxolitinib has become available in Hungary since 2015. Beside its high efficacy in spleen volume and in reduction of myelofibrosis-associated symptoms, this novel therapy also exerts a disease modifying effect and, therefore, ruxolitinib may improve the life expectancy too. Treatment approach of myelofibrosis has been changed these years, which gives a reason for this summary. Orv. Hetil., 2016, 157(39), 1547-1556. PMID- 27667292 TI - RUNX1 truncation resulting from a cryptic and novel t(6;21)(q25;q22) chromosome translocation in acute myeloid leukemia: A case report. AB - Fluorescence in situ hybridization examination of a pediatric AML patient whose bone marrow cells carried trisomy 4 and FLT3-ITD mutation, demonstrated that part of the RUNX1 probe had unexpectedly moved to chromosome band 6q25 indicating a cryptic t(6;21)(q25;q22) translocation. RNA sequencing showed fusion of exon 7 of RUNX1 with an intergenic sequence of 6q25 close to the MIR1202 locus, something that was verified by RT-PCR together with Sanger sequencing. The RUNX1 fusion transcript encodes a truncated protein containing the Runt homology domain responsible for both heterodimerization with CBFB and DNA binding, but lacking the proline-, serine-, and threonine-rich (PST) region which is the transcription activation domain at the C terminal end. Which genetic event (+4, FLT3-ITD, t(6;21)-RUNX1 truncation or other, undetected acquired changes) was more pathogenetically important in the present case of AML, remains unknown. The case illustrates that submicroscopic chromosomal rearrangements may accompany visible numerical changes and perhaps should be actively looked for whenever a single trisomy is found. An active search for them may provide both pathogenetic and prognostic novel information. PMID- 27667295 TI - [Insight into the training of patients with idiopathic inflammatory myopathy]. AB - Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis. Orv. Hetil., 2016, 157(39), 1557-1562. PMID- 27667296 TI - [The role of physical activity in health promotion of healthcare workers]. AB - INTRODUCTION: The health status of doctors, nurses and any other professionals working in the healthcare sector influences the quality of their work. Therefore, health promotion of healthcare workers is not only an occupational health program but it can be considered as an action towards improving the quality of care. AIM: The current study was designed to assess the efficacy of a health promotion intervention among healthcare workers after health status assessment. METHOD: Before and after the intervention a self-assessment questionnaire-based health survey and physical status examination were performed. Members of the intervention group were offered to use fitness facilities, professional psychological help, dietary counselling, and dental consultation. RESULTS: The intervention program lasted for 12 months with the participation of 79 health care professionals (based on their decision being in the intervention or in the control group). Significant decrease was found in the abdominal perimeter in participants of the intervention group and they ran a longer distance on the 12 minute-long-run test at the end of the study. CONCLUSIONS: The positive effect of regular physical exercise as part of active lifestyle has been demonstrated not only in the increase of physical capacity, but in the change of body shape, as well. Orv. Hetil., 2016, 157(39), 1563-1570. PMID- 27667298 TI - [Miscellaneous]. PMID- 27667297 TI - [An unusual cause of the hand cyst: finger dirofilariasis]. AB - Dirofilariasis is a zoonosis affecting dogs and cats. It can be transmitted to human by mosquito bites. Because of the local inflammation caused by the parasite, a lump may develop. The authors present a case of a 13-year-old boy, who was diagnosed with dirofilariasis in association with a cyst located on the middle finger of the right hand. During physical examination, a lump on the extensor surface of the middle phalanx of the right middle finger was found. Soft tissue ultrasound was performed, which indicated the presence of a worm in the cyst. The cyst was surgically removed under local anesthesia and with parasitology test Dirofilaria repens infection was confirmed. The child had no complains or symptoms during recovery after the surgery. A solitary growth developing on the fingers of the hand often presents a differential diagnostic problem. Ultrasound can be greatly helpful in the preoperative diagnosis. Orv. Hetil., 2016, 157(39), 1571-1574. PMID- 27667299 TI - Low-density lipoprotein cholesterol in a global cohort of 57,885 statin-treated patients. AB - BACKGROUND AND AIMS: There is an inconsistency between international guidelines on lipid-lowering treatment regarding whether to pursue LDL-C treatment targets or to focus on the intensity of treatment. While either approach is attractive, there is no recent global data on actual LDL-C values, treatment targets attained, and the intensity of treatment in statin-treated patients. We aimed to determine and compare the extent of treatment target attainment globally using standardized data collection. METHODS: Analyses were based on the Dyslipidemia International Study (DYSIS), a cross-sectional study documenting statin-treated outpatients throughout 30 countries worldwide (across Europe, the Middle East, Canada, Africa, and Asia). Patients were classified as being at very high, high, or non-high cardiovascular risk based on the 2011 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines. RESULTS: Data were available for a total of 57,885 patients with a median LDL-C value of 98.2 mg/dl (IQR: 76.6, 125.7 mg/dl). Overall, only 26.8% of patients were documented to have attained their risk-based target LDL-C level. Of the 76% of patients who were classified as being at very high risk, only 21.7% attained their LDL-C goal. Globally, the median distance to target was 33.0 mg/dl, ranging from 18.8 to 42.1 mg/dl across countries. We calculated that a further LDL-C reduction of just 10 mg/dl would result in an 11% increase in the proportion of very-high-risk and high-risk patients attaining their target level (9% for non-high risk patients). CONCLUSIONS: In spite of statin therapy, LDL-C values were high, with a substantial distance to target that was even more pronounced in (very) high risk patients. These results call for the optimization of existing treatment strategies and a collaborative effort to improve the impact of treatment guidance on clinical practice. PMID- 27667300 TI - The risk of bleeding after invasive procedures in patients with cirrhosis with severe coagulopathy. PMID- 27667301 TI - Identification of differentially expressed transcripts targeted by the knockdown of endogenous IFITM3. AB - Interferon inducible transmembrane protein 3 (IFITM3) is a double transmembrane protein. As a member of the IFITM family, IFITM3 can be upregulated by interferon (IFN) to be involved in various biological processes. In order to determine whether gene expression profiles can be altered by a lack of IFITM3, the present study used shRNAs lentivirus for knocking down the endogenous expression of IFITM3 in human HeLa cells and human whole genome microarrays to obtain gene expression profiles. A total of 1,011 downregulated transcripts and 615 upregulated transcripts were identified using the Agilent expression platform. The identified transcripts were involved in multiple pathways, including the complement pathways, and the antigen processing and presentation pathway. The present study identified the transcripts, which were affected by the downregulation of endogenous IFITM3 and the pathways they were involved in. These findings may lead to an improved understanding of the biological functions of IFITM3. PMID- 27667303 TI - Lipoprotein immunoproteomics question the potential of Staphylococcus aureus TLR2 agonists as vaccine antigens. AB - Toll-like receptor 2 (TLR2) is regarded as the major innate immunity sensor in infections caused by the Gram-positive bacterial pathogen Staphylococcus aureus. However, previous studies on the roles of TLR2 in S. aureus infections have been elusive and in part contradictory. It has remained particularly unclear if bacterial lipoproteins, the major TLR2 ligands, could serve as antigens with intrinsic adjuvant property for the development of protective vaccines. The study by Vu et al. published in this issue of Proteomics analyzed the antibody and T cell responses in human sera against major S. aureus lipoproteins. Notably, even lipoproteins released to culture filtrates at similar levels as established immunodominant antigens elicited only very weak or no detectable antibody and T cell responses, indicating that the potent TLR2-stimulating capacity of S. aureus lipoproteins does not promote and may rather impair robust immune responses so lipoprpteins. Among several potential explanations it is tempting to speculate that the role of TLR2 in S. aureus infections may be more complex and more ambiguous than previously thought. The study of Vu et al. may thus provoke more detailed investigations on the roles of lipoproteins and TLR2 in innate and adaptive immunity against bacterial pathogens. PMID- 27667304 TI - Comparative electrostatic analysis of adenylyl cyclase for isoform dependent regulation properties. AB - The enzyme adenylyl cyclase (AC) plays a pivotal role in a variety of signal transduction pathways inside the cell, where it catalyzes the cyclization of adenosine triphosphate (ATP) into the second-messenger cyclic adenosine monophosphate (cAMP). Among other roles, AC regulates processes involved in neural plasticity, innervation of smooth muscles of the heart and the endocrine system of the pancreas. The functional diversity of AC is manifested in its different isoforms, each having a specific regulation pattern. There is an increasing amount of data available concerning the regulatory properties of AC isoforms, however little is known about the interactions on a structural level. Here, we conducted a comparative electrostatic analysis of the catalytic domains of all nine transmembrane AC isoforms with the aim of detecting, verifying and predicting the binding sites of molecular regulators on AC. The results provide support for the positioning of the binding site of the inhibitory protein Gi alpha at a pseudo-symmetric position to the stimulatory Gs alpha binding site. They also provide a structural interpretation of the Gbetagamma interaction with ACs 2, 4, and 7 and suggest a new binding site for RGS2. Comparison of the small molecule binding sites on AC shows that overall they have high electrostatic similarity, but regions of electrostatic differences are identified. These could provide a basis for the development of novel compounds with isoform-specific modulatory effects on AC. Proteins 2016; 84:1844-1858. (c) 2016 Wiley Periodicals, Inc. PMID- 27667305 TI - Prevalence and epidemiology of tinea pedis and toenail onychomycosis and antifungal susceptibility of the causative agents in patients with type 2 diabetes in Turkey. AB - BACKGROUND: Diabetes patients are particularly susceptible to fungal infections because their vascular and immunological systems are compromised. OBJECTIVES: The present study aimed to determine prevalences of tinea pedis and onychomycosis, factors predisposing to their development, and antifungal susceptibilities of causative fungal species against fluconazole, itraconazole, and terbinafine in patients with type 2 diabetes mellitus (DM). METHODS: Study groups were defined according to hemoglobin A1C rates of >=6.5% for the diabetes group and <=5.7% for control subjects. A total of 600 diabetes subjects and 152 control subjects were evaluated. Rates of onychomycosis and tinea pedis in diabetes patients, and associations with age, gender, blood glucose level, duration of diabetes and serum lipid profile were investigated, as were the distribution and antifungal susceptibility of agents isolated. RESULTS: Patients with onychomycosis and/or tinea pedis numbered 85 in the diabetes group and nine in the control group (P = 0.006). The development of onychomycosis or tinea pedis was significantly related to increasing age and male gender. Although the most common agents were dermatophytes, non-dermatophyte fungal isolates were not uncommon. Terbinafine was the most effective drug against dermatophytes but was invalid for non dermatophyte isolates by in vitro antifungal susceptibility testing. CONCLUSIONS: The development of onychomycosis or tinea pedis was significantly related to type 2 DM, increasing age, and male gender. The most common isolate was Trichophyton rubrum. The isolation and identification of the fungus is important to the effective management of tinea pedis and onychomycosis in diabetes patients because non-dermatophyte fungi can cause these infections. PMID- 27667307 TI - Felix Natalis, O BSF The British Skin Foundation 20th Anniversary: an introduction. PMID- 27667306 TI - Advanced Separators for Lithium-Ion and Lithium-Sulfur Batteries: A Review of Recent Progress. AB - Li-ion and Li-S batteries find enormous applications in different fields, such as electric vehicles and portable electronics. A separator is an indispensable part of the battery design, which functions as a physical barrier for the electrode as well as an electrolyte reservoir for ionic transport. The properties of the separators directly influence the performance of the batteries. Traditional polyolefin separators showed low thermal stability, poor wettability toward the electrolyte, and inadequate barrier properties to polysulfides. To improve the performance and durability of Li-ion and Li-S batteries, development of advanced separators is required. In this review, we summarize recent progress on the fabrication and application of novel separators, including the functionalized polyolefin separator, polymeric separator, and ceramic separator, for Li-ion and Li-S batteries. The characteristics, advantages, and limitations of these separators are discussed. A brief outlook for the future directions of the research in the separators is also provided. PMID- 27667308 TI - Filaggrin failure - from ichthyosis vulgaris to atopic eczema and beyond. AB - The main proteinaceous component of the keratohyalin granules within the granular layer keratinocytes of the epidermis is the giant, repetitive polyprotein profilaggrin. When granular layer cells commit to terminal differentiation to form the flattened squames of the stratum corneum, profilaggrin is rapidly cleaved into multiple copies of the 37 kDa filaggrin monomer, which binds to and condenses the keratin cytoskeleton, thereby facilitating cellular compression. Within the stratum corneum, filaggrin is broken down to form natural moisturising factor, a pool of amino acids and derivatives thereof that exerts multiple effects. Filaggrin is therefore essential for normal stratum corneum biogenesis and physiology. In 2006, the McLean group identified the first loss-of-function mutations in the filaggrin gene (FLG) as the cause of the common monogenic genodermatosis ichthyosis vulgaris (IV). In parallel, they showed by multiple methods that these mutations, carried by up to 10% of various human populations are the major genetic predisposing factor for atopic dermatitis (eczema) and all of the associated allergic phenotypes that constitute the atopic diathesis. This paradigm-shifting work showed that skin barrier deficiency is a major early event in the pathophysiology of eczema and allergy. PMID- 27667302 TI - WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects. AB - Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation. PMID- 27667310 TI - The role of skin and gut microbiota in the development of atopic eczema. AB - Conventional culture-based studies have suggested that a reduction in microbial exposure in early life predisposes to atopic eczema and allergies. However, molecular microbiological methods have shown that conventional culture fails to grow around 80% of the bacterial flora. More recent work reviewed in this paper has employed next generation sequencing to study the influence of the gut and skin microbiota, both with regard to the risk of developing atopic eczema but also the role of pathogenic and commensal bacteria in established disease. Birth cohorts investigating the gastrointestinal tract reported reduced faecal microbiota diversity among those who later developed atopic eczema, using gel electrophoresis, real-time PCR or 16S ribosomal RNA gene pyrosequencing. However, the inverse association with reduced faecal bacterial diversity was not confirmed in cross-sectional studies among patients with established atopic eczema. Only two studies investigated the cutaneous microbiota in a longitudinal study design and both were unable to provide evidence that Staphylococcus aureus colonisation precedes the development of atopic eczema. Next generation sequencing has confirmed the cross-sectional association between atopic eczema and S. aureus colonisation. The two studies that used this approach have also shown that disease flares are associated with a significant fall in skin microbiota diversity and an increase in the relative abundance of both S. aureus and epidermidis. Interestingly, S. aureus elimination does not appear to be the main reason why atopic eczema improves after a flare and antimicrobial and anti inflammatory therapy enhances bacterial diversity. Further, well-phenotyped birth cohorts that take key confounders, such as antibiotic exposure, into account are required. PMID- 27667309 TI - Translating translation into patient benefit for atopic eczema. AB - This review considers, in the context of British Skin Foundation (BSF)-funded translational research into atopic eczema conducted in Newcastle, the complex interactions between clinical and non-clinical scientists in both academia and industry and how this may have impacted on clinical care. However, research in individual centres does not occur in isolation and clinically relevant outcomes from collaborative research are increasingly supported through regional and national networks. This is illustrated by our trial of azathioprine in adults with atopic eczema conducted across centres in the North East of England that employed pharmacogenetic dosimetry. Correspondingly the formation of a UK Translational Network for Translational Research in Dermatology (UK TREND) has facilitated the development of a UK-wide network to support atopic eczema projects based on an e-Delphi prioritisation exercise. PMID- 27667311 TI - Lipid-specific T cells and the skin. AB - Langerhans cells express constitutively high levels of CD1a, a member of the CD1 family of molecules which are known to present lipid antigens to T cells. Whilst much human skin immunology research has focussed on the function of T cells which recognise peptides presented by HLA molecules, in contrast few studies have addressed the role of CD1a and lipid antigens in the pathogenesis of inflammatory skin disease. House dust mite and bee and wasp venom extracts were found to generate CD1a reactivity, but paradoxically this function was within the protein and not lipid fraction. This unexpected finding was explained by the presence of phospholipases within the house dust mite and insect venoms which generated antigenic lipids on contact with skin. The lipids then bind to CD1a on Langerhans cells which are recognised by T cells, which in turn contribute to skin inflammation. This newly identified pathway of skin inflammation defines several potential points for therapeutic intervention. PMID- 27667312 TI - Oxidative stress and ageing. AB - Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015), but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the SDHA and SDHB catalytic subunits of complex II respectively. In addition there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells, our study being the first to investigate these differences with senescence and skin age. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. Our study provides a future potential biomarker for monitoring the progression of skin ageing. PMID- 27667314 TI - British Skin Foundation, Skin Deep - 20 Years of Research, 20th Anniversary Conference, 13th October 2016, Royal College of Physicians, London, U.K. PMID- 27667316 TI - Spotlights on our sister journals: Chem. Eur. J. 41/2016. PMID- 27667313 TI - Vitamin D, vitamin A, the primary melanoma transcriptome and survival. AB - Survival from melanoma is influenced by several, well-established clinical and histopathological factors, e.g. age, Breslow thickness and microscopic ulceration. We (the Section of Epidemiology and Biostatistics, University of Leeds) have carried out research to better understand the biological basis for these observations. Preliminary results indicated a protective role for vitamin D in melanoma relapse and that higher vitamin D was associated with thinner primary melanomas. Funding from the British Skin Foundation enabled JNB to establish a study of the effects of vitamin A in melanoma. The results suggested that vitamin A could reduce the protective effect of vitamin D in terms of overall survival. Therefore, we propose that vitamin D3 supplementation alone might be preferable to combined multivitamin preparations, where vitamin D supplementation is deemed to be appropriate. Proving a causal link between vitamin D and melanoma-specific survival is challenging. We have shown limited evidence of causation in a Mendelian randomization experiment (described in more detail later). Recent work in Leeds has also shown that higher vitamin D may be protective for microscopic ulceration. Taken together, vitamin D appears to be associated with less aggressive primary melanomas and may itself influence outcome. We continue to explore the role of vitamin D in melanoma survival and the optimum levels that might be crucial. PMID- 27667315 TI - Calcium-Sensing Receptor and Transient Receptor Ankyrin-1 Mediate Emesis Induction by Deoxynivalenol (Vomitoxin). AB - The common foodborne mycotoxin deoxynivalenol (DON, vomitoxin) can negatively impact animal and human health by causing food refusal and vomiting. Gut enteroendocrine cells (EECs) secrete hormones that mediate DON's anorectic and emetic effects. In prior work utilizing a cloned EEC model, our laboratory discovered that DON-induced activation of calcium-sensing receptor (CaSR), a G coupled protein receptor (GPCR), and transient receptor ankyrin-1 (TRPA1), a transient receptor potential (TRP) channel, drives Ca2+-mediated hormone secretion. Consistent with these in vitro findings, CaSR and TRPA1 mediate DON induced satiety hormone release and food refusal in the mouse, an animal model incapable of vomiting. However, the roles of this GPCR and TRP in DON's emetic effects remain to be determined. To address this, we tested the hypothesis that DON triggers emesis in mink by activating CaSR and TRPA1. Oral gavage with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate; AITC) rapidly elicited emesis in the mink in dose-dependent fashion. Oral pretreatment of the animals with the CaSR antagonist NPS-2143 or the TRP antagonist ruthenium red (RR), respectively, inhibited these responses. Importantly, DON-induced emesis in mink was similarly inhibited by oral pretreatment with NPS-2143 or RR. In addition, these antagonists suppressed concurrent DON-induced elevations in plasma peptide YY3-36 and 5-hydroxytryptamine-hormones previously demonstrated to mediate the toxin's emetic effects in mink. Furthermore, antagonist co-treatment additively suppressed DON-induced emesis and peptide YY 3-36 release. To summarize, the observations here strongly suggest that activation of CaSR and TRPA1 might have critical roles in DON-induced emesis. PMID- 27667317 TI - Validation of the Chinese version of the Anticipatory and Consummatory Interpersonal Pleasure Scale. AB - Social anhedonia, the reduced capacity for social and interpersonal pleasure, often accompanies several forms of psychopathology. The goal of the present study was to validate the Chinese translation of the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS), a promising new tool for the assessment of individual differences in social pleasure. The Chinese versions of the ACIPS, the Temporal Experience of Pleasure Scale (TEPS), and the Schizotypal Personality Questionnaire (SPQ) were administered to 389 nonclinical adults. Factor analysis revealed that a four-factor structure accounted for nearly 53% of the variance, and the factors were consistent with those identified from factor analyses of the ACIPS in Western (U.S.) samples. The ACIPS measure showed high internal consistency as well. Correlational analysis revealed evidence of convergent validity. Individuals who scored high on the ACIPS were more likely to score high on measures of anticipatory and consummatory pleasure. Moreover, ACIPS total scores were inversely associated with scores on the No Close Friends subscale and the Constricted Affect subscale of the Schizotypal Personality Questionnaire (SPQ). Taken together, the findings suggest that the Chinese translation of the ACIPS is a reliable, valid measure that can be used to assess individual differences in the capacity to experience social and interpersonal pleasure in Chinese individuals. PMID- 27667318 TI - The impact of the context and recruitment materials on nondonors' willingness to donate blood. AB - BACKGROUND: Anxiety is a frequently cited barrier to blood donor recruitment. Although the mere presence of donation paraphernalia can heighten anxiety for some individuals, such stimuli are a necessary and unavoidable part of donation. Drawing on France and colleagues' research on tailored donor education and coping materials, the current study assessed whether modifying recruitment materials could improve donor recruitment in a context where anxiety is heightened. STUDY DESIGN AND METHODS: A field study comprising a 2 (presence or absence of a mobile blood collection unit [MCU]) * 2 (recruitment brochure: standard, coping) between subjects design was conducted with 922 nondonors who believed themselves eligible to donate blood. In either the presence or absence of the MCU, participants received a standard or modified recruitment brochure modeled on France and colleagues' education and coping materials. Donation anxiety, attitude, subjective norm, self-efficacy, and intention were assessed, and donation behavior was tracked for 30 days. RESULTS: Participants who were assessed in the presence of the MCU reported heightened anxiety, and female participants reported decreased self-efficacy. The coping brochure improved self-efficacy, heightened the intention to donate in the presence of the MCU, and promoted blood donation behavior relative to the standard brochure. Path analyses supported a model in which, in the presence of the MCU, the coping brochure boosted self-efficacy and led to increased donation intention and behavior. CONCLUSIONS: In a context in which donation-related anxiety is heightened, provision of materials that address prospective donor concerns and suggest coping strategies can bolster self efficacy and promote recruitment. PMID- 27667319 TI - Tying a Molecular Overhand Knot of Single Handedness and Asymmetric Catalysis with the Corresponding Pseudo-D3-Symmetric Trefoil Knot. AB - We report the stereoselective synthesis of a left-handed trefoil knot from a tris(2,6-pyridinedicarboxamide) oligomer with six chiral centers using a lanthanide(III) ion template. The oligomer folds around the lanthanide ion to form an overhand knot complex of single handedness. Subsequent joining of the overhand knot end groups by ring-closing olefin metathesis affords a single enantiomer of the trefoil knot in 90% yield. The knot topology and handedness were confirmed by NMR spectroscopy, mass spectrometry, and X-ray crystallography. The pseudo-D3-symmetric knot was employed as an asymmetric catalyst in Mukaiyama aldol reactions, generating enantioselectivities of up to 83:17 er, which are significantly higher than those obtained with a comparable unknotted ligand complex. PMID- 27667321 TI - Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice. AB - Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice. In addition, these proteins have led to reduced lymphocytic infiltration and decreased islet damage and inflammation. The curative effect was found to be associated with the suppression of release of tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN-gamma), and increased production of interleukin (IL)-4, IL-5 and IL-10 cytokines by the splenocytes of the diabetic mice. Insulin specific IgG1 and antigen-specific IgE antibodies were found to be elevated in the sera of mice treated with rWbL2 and rBmALT-2 proteins. From the findings in this study, it can be envisaged that both of these filarial immunomodulatory proteins have the potential to ameliorate T1D by altering the regulatory immune responses. PMID- 27667320 TI - Why cognitive penetration of our perceptual experience is still the most plausible account. AB - To what extent is our perceptual experience influenced by higher cognitive phenomena like beliefs, desires, concepts, templates? Given recent arguments against the possibility of cognitive penetration, we present striking evidence against the impenetrability claims. The weak impenetrability claim cannot account for (1) extensive structural feedback organization of the brain, (2) temporally very early feedback loops and (3) functional top-down processes modulating early visual processes by category-specific information. The strong impenetrability claim could incorporate these data by widening the "perceptual module" such that it includes rich but still internal processing in a very large perceptual module. We argue that this latter view leads to an implausible version of a module. Therefore, we have to accept cognitive penetration of our perceptual experience as the best theoretical account so far given the available empirical evidence. We outline that this does not have any problematic consequences for the relation between perception and cognition. PMID- 27667322 TI - Standardization of capillary electrophoresis for diagnosis of fragile X syndrome in the Brazilian public health system. AB - Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability. The most common etiology of the syndrome is expansion and methylation of a CGG trinucleotide at chromosome region Xq27.3 involving FMR1 (fragile X mental retardation 1 gene). This disorder is commonly underdiagnosed in children and adolescents, given the high clinical variability. In Brazil, molecular diagnosis of FXS by CE does not exist in the public health system. The current standard for separation and identification of DNA fragment sizes is 50 cm CE, which is uncommon in public genotyping laboratories. This study describes the standardization of 36 cm CE for fragment analysis of samples from patients with intellectual disability suggestive of FXS. Genomic dsDNA was isolated from patients and amplified by PCR using the FMR1 AmplideX(r) Kit. It was then possible to detect changes in repeat length of FMR1, such as full mutation and premutation. Thus, the proposed standardization proved to be effective for the diagnosis of FXS, permitting suitable genetic counseling for families. Inclusion of molecular testing such as this in the Brazilian public health service bridges the gap between available technologies and effective diagnosis, universalizing access to genetic testing in central Brazil. PMID- 27667323 TI - Suspicious case with laser-induced chrysiasis: Hyperpigmentation following laser toning with neodymium:yttrium-aluminum-garnet in a woman previously treated with microneedle therapy system using gold. PMID- 27667324 TI - Nadolol reduces insulin sensitivity in liver cirrhosis: a randomized double-blind crossover trial. AB - BACKGROUND: Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Noncardioselective beta-blockers not only reduce portal hypertension and prevent variceal bleeding in cirrhosis but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether nonselective beta-blockade with nadolol impairs glucose metabolism in liver cirrhosis. METHODS: A randomized, double-blind, placebo-controlled crossover trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index, and glucose tolerance. Stable cirrhotic patients of mixed etiology underwent an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n = 16) and a 75-g oral glucose tolerance test (n = 17). These measurements were conducted twice (after 3 months of treatment with nadolol or placebo and, after a 1-month washout period, after 3 months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3-month treatment. RESULTS: Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7 +/- 10.1 vs 99.6 +/- 10.3 MUL/kg fat-free mass.min-1 .(mU/L)-1 , P = .005). Insulin secretion was unchanged (P = .24), yielding a lower disposition index with nadolol (6083 +/- 2007 vs 8692 +/- 2036, P = .050). There was no change in total body fat or plasma catecholamines. A 2-hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8 +/- 0.9 vs 9.9 +/- 0.9 mmol/L, P = .035). CONCLUSIONS: Nadolol significantly worsened insulin sensitivity, glycemia, and disposition index in patients with liver cirrhosis. These findings may have significant clinical implications because cirrhosis is already associated with an increased prevalence of diabetes. PMID- 27667325 TI - Identification of bacterial pathogens and antimicrobial resistance directly from clinical urines by nanopore-based metagenomic sequencing. AB - OBJECTIVES: The introduction of metagenomic sequencing to diagnostic microbiology has been hampered by slowness, cost and complexity. We explored whether MinION nanopore sequencing could accelerate diagnosis and resistance profiling, using complicated urinary tract infections as an exemplar. METHODS: Bacterial DNA was enriched from clinical urines (n = 10) and from healthy urines 'spiked' with multiresistant Escherichia coli (n = 5), then sequenced by MinION. Sequences were analysed using external databases and bioinformatic pipelines or, ultimately, using integrated real-time analysis applications. Results were compared with Illumina data and resistance phenotypes. RESULTS: MinION correctly identified pathogens without culture and, among 55 acquired resistance genes detected in the cultivated bacteria by Illumina sequencing, 51 were found by MinION sequencing directly from the urines; with three of the four failures in an early run with low genome coverage. Resistance-conferring mutations and allelic variants were not reliably identified. CONCLUSIONS: MinION sequencing comprehensively identified pathogens and acquired resistance genes from urine in a timeframe similar to PCR (4 h from sample to result). Bioinformatic pipeline optimization is needed to better detect resistances conferred by point mutations. Metagenomic sequencing-based diagnosis will enable clinicians to adjust antimicrobial therapy before the second dose of a typical (i.e. every 8 h) antibiotic. PMID- 27667326 TI - Ion-Exchange-Induced 2D-3D Conversion of HMA1-x FAx PbI3 Cl Perovskite into a High-Quality MA1-x FAx PbI3 Perovskite. AB - High-quality phase-pure MA1-x FAx PbI3 planar films (MA=methylammonium, FA=formamidinium) with extended absorption and enhanced thermal stability are difficult to deposit by regular simple solution chemistry approaches owing to crystallization competition between the easy-to-crystallize but unwanted delta FAPbI3 /MAPbI3 and FAx MA1-x PbI3 requiring rigid crystallization conditions. Here A 2D-3D conversion to transform compact 2D mixed composition HMA1-x FAx PbI3 Cl perovskite precursor films into 3D MA1-x FAx PbI3 (x=0.1-0.9) perovskites is presented. The designed Cl/I and H/FA(MA) ion exchange reaction induced fast transformation of compact 2D perovskite film, helping to form the phase-pure and high quality MA1-x FAx PbI3 without delta-FAPbI3 and MAPbI3 impurity. In all, we successfully developed a facile one-step method to fabricate high quality phase pure MA1-x FAx PbI3 (x=0.1-0.9) perovskite films by 2D-3D conversion of HMA1-x FAx PbI3 Cl perovskite. This 2D-3D conversion is a promising strategy for lead halide perovskite fabrication. PMID- 27667327 TI - Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia. AB - BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C-reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP-D were compared with healthy controls. RESULTS: Baseline values of circulating SP-D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P > 0.05). After initiation of chemotherapy, a significant reduction in SP-D levels was observed at all time points: 704 ng/ml at day 8, 413 ng/ml at day 15, 395 ng/ml at day 22, and 520 ng/ml at day 29 (all, P < 0.05). No significant associations between SP-D values, the occurrence of mucosal toxicity, or infectious morbidity were observed. However, loss of circulating SP-D from days 8 to 15 was associated with more systemic inflammation, and lower SP-D values at day 15 were associated with elevated intestinal mucositis scores (P < 0.05). CONCLUSIONS: The current study supports the hypothesis that the detrimental effect of chemotherapy on patients' immune functions includes decreased circulating levels of innate mucosal molecules such as SP-D, potentially aggravating mucosal and systemic inflammatory responses. PMID- 27667329 TI - Effects of a Japan Diet Intake Program on Metabolic Parameters in Middle-Aged Men. AB - AIM: We conducted a pilot study to clarify the effects of the Japan Diet nutritional education program on metabolic risk factors for atherosclerotic cardiovascular disease in middle-aged men who were brought up in the westernized dietary environment of modern Japan. METHODS: Thirty-three men, 30-49 years of age, attended a nutrition education class to learn food items and recommended volumes comprising the Japan Diet (more fish, soybeans and soy products, vegetables, seaweed, mushrooms and unrefined cereals, and less animal fat, meat and poultry with fat, sweets, desserts and snacks, and alcoholic drinks), and were encouraged to consume the Japan Diet for 6 weeks. Anthropometric and biochemical parameters were measured and 3-day weighted dietary records were kept before and at completion of the intervention. RESULTS: Ninety-one percent of participants showed improvements in more than one cardiovascular risk factor after 6 weeks. Body weight, serum low density lipoprotein (LDL) cholesterol, malondialdehyde modified (MDA)-LDL and triglyceride concentrations decreased significantly, while high density lipoprotein cholesterol was unchanged. Fish, soy, and sum of seaweed, mushrooms and konjak intakes doubled, and green and yellow vegetable intakes also increased as compared to baseline. Meanwhile, intakes of refined cereals, meat and poultry, sweets, desserts and snacks, and margarine and shortening decreased. Total energy, lipid, and saturated and monounsaturated fatty acid intakes decreased, while n-3 polyunsaturated fatty acid, dietary fiber, beta-carotene, vitamins D and K, potassium, and magnesium increased, with no change in sodium intake. CONCLUSIONS: The Japan Diet is suggested to improve atherosclerotic cardiovascular disease risk factors in middle-aged Japanese men.The clinical trial registration number: UMIN000020639. PMID- 27667328 TI - Fifty-year Time Trends in Blood Pressures, Body Mass Index and their Relations in a Japanese Community: The Circulatory Risk in Communities Study (CIRCS). AB - AIM: Data for long-term trends in blood pressures, body mass index (BMI), and their relations are needed to set future intervention priorities for prevention of cardiovascular disease. The objective of this study was to investigate these trends revealed by repeated cross-sectional surveys conducted from 1963 to 2013 in a Japanese community. METHODS: Men and women aged 40-79 years who participated in annual cardiovascular checkups were enrolled, and the number of participants ranged between 1,776 and 2,366 with consistently high participation rates for both sexes aged 60-69 years. Sex- and age-specific mean systolic and diastolic blood pressures were calculated using mixed effects modeling for repeated measurement, and the prevalence of hypertension with and without obesity (BMI >= 25 kg/m2) were also calculated. RESULTS: Sex- and age-specific mean systolic and diastolic blood pressures declined irrespective of antihypertensive medication use in both men and women from 1963-1966 to 2009-2013, while mean BMI increased among men of all ages and women of ages 60-69 and 70-79 years. For both sexes aged 60-69 years, the prevalence of hypertension with obesity increased, but the prevalence of hypertension without obesity was still higher that with obesity. CONCLUSIONS: Despite the transition to increased BMI levels, targeting non to obese hypertension remains important in addition to targeting obese hypertension for cardiovascular disease prevention. PMID- 27667330 TI - Brief education to promote maternal influenza vaccine uptake: A randomized controlled trial. AB - BACKGROUND: Although pregnant women are the highest priority group for seasonal influenza vaccination, maternal influenza vaccination rates remain suboptimal. The purpose of this study was to evaluate the effect of a brief education intervention on maternal influenza vaccine uptake. METHODS: During the 2013-14 and 2014-15 influenza seasons, we recruited 321 pregnant women from the antenatal clinics of 4 out of 8 public hospitals in Hong Kong with obstetric services. Hospitals were geographically dispersed and provided services to pregnant women with variable socioeconomic backgrounds. Participants were randomized to receive either standard antenatal care or brief one-to-one education. Participants received telephone follow-up at 2 weeks postpartum. The primary study outcome was self-reported receipt of influenza vaccination during pregnancy. The secondary outcomes were the proportion of participants who initiated discussion about influenza vaccination with a health care professional and the proportion of participants who attempted to get vaccinated. RESULTS: Compared with participants who received standard care, the vaccination rate was higher among participants who received brief education (21.1% vs. 10%; p=0.006). More participants in the education group initiated discussion about influenza vaccination with their HCP (19.9% vs. 13.1%; p=0.10), but the difference was not statistically significant. Of participants who did not receive the influenza vaccine (n=271), 45 attempted to get vaccinated. A significantly higher proportion of participants who attempted to get vaccinated were in the intervention group (82.2% vs. 17.8%; p<0.001). If participants who had attempted vaccination had received the vaccine, vaccination rates would have been substantially higher (44.1% vs. 15%; p<0.001). Twenty-six participants were advised against influenza vaccination by a healthcare professional, including general practitioners, obstetricians, and nurses. CONCLUSION: Although brief education was effective in improving vaccination uptake among pregnant women, overall vaccination rates remain suboptimal. Multicomponent approaches, including positive vaccination recommendations by healthcare professionals, are needed to promote maternal influenza vaccination. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01772901). PMID- 27667331 TI - A paper-based immunoassay to determine HPV vaccination status at the point-of care. AB - OBJECTIVE: To develop and evaluate a paper-based point-of-care HPV serology test to determine if an individual has received two or more HPV immunizations. METHODS: The paper-based immunoassay was constructed using a nitrocellulose lateral flow strip with adsorbed HPV16 virus-like particles serving as the capturing moiety. Three capture zones containing virus-like particles were placed in series to allow for visual discrimination between high and low HPV16 plasma antibody concentrations. A plasma separation membrane was used to allow whole blood to be applied directly to the assay. All reagents were dried on glass fiber pads during device fabrication and were rehydrated with buffer at the time of use. A pilot study consisting of 35 subjects with a history of zero, one, two or three HPV vaccines was conducted to evaluate the immunoassay. The completed paper based immunoassays were scanned for visual interpretation by three researchers who were blinded to the true results and separately evaluated quantitatively using MATLAB. RESULTS: For the 28 tests valid for analysis, fifteen subjects reported receiving two or more HPV vaccines, three reported receiving one, and ten reported having no HPV vaccinations. The paper-based immunoassays for all fifteen subjects who reported having received two or more HPV vaccines were judged positive by all researchers. Twelve of the thirteen tests from individuals reporting one or zero vaccinations were deemed negative by all observers. One test from an unvaccinated individual was judged positive by two out of three reviewers. Quantitatively, all tests were correctly separated between the two groups. CONCLUSIONS: We successfully designed and tested a HPV serology test amenable to the point-of-care. The device showed promising results in a pilot study for discriminating between those who received two or more HPV vaccinations and those who did not. Furthermore, this device offers a platform for producing other semi-quantitative point-of-care serological tests. PMID- 27667333 TI - Rare earth and trace element signatures for assessing an impact of rock mining and processing on the environment: Wisniowka case study, south-central Poland. AB - A detailed hydrogeochemical study was performed in the Wisniowka mining area (south-central Poland). This covered three acid pit bodies, historic tailings acid ponds, acid pools, and additionally two neighboring rivers. All these acid mine drainage (AMD) waters are characterized by the pH in the range of 1.7 (pools) to 3.5 (tailings ponds). The most interesting is the Podwisniowka acid pit lake that shows a very low pH (2.2-2.5) and very high concentrations of SO42- (2720-5460 mg/L), Fe (545-1140 mg/L), Al (86.2 mg/L), As (9603-24,883 MUg/L), Co (1317-3458 MUg/L), Cr (753-2047 MUg/L), Cu (6307-18,879 MUg/L), Ni (1168-3127 MUg/L), and rare earth element (REE) (589-1341 MUg/L). In addition, seeps that drain the Podwisniowka mine tailings and partly aggregate piles form strong acid pools in the mining area. Along with these pools, in which As and REE contents reach 369,726 and 6288 MUg/L, respectively, these waters are among the most distinctive As- and REE-rich AMD surface waters across the world. It is noteworthy that the Podwisniowka acid pit lake and Wisniowka Duza acid pit sump exhibit different element signatures and REE concentration patterns normalized to North American Composite Shale (NASC): the Podwisniowka acid pit lake always shows a characteristic roof-shaped medium REE (MREE) profile with distinct enrichments in Gd, Eu, and Tb whereas the other one displays a step-shaped heavy REE (HREE) profile with positive Tb and Gd anomalies. The REE undergo fractionation during weathering and the subsequent leaching of dissolved and suspended fractions from rocks to acid water bodies where these and other elements are further fractionated by geochemical processes. This study shows that the individual REE have greater affinities for Mn, HREE for Fe and SO42-, and only La and Ce for Al. This specific water geochemistry has enabled us to (i) pinpoint the location of AMD "hot spots" originated from quartzite mining and processing operations conducted by current and previous mining companies, (ii) predict the directions and effects of future strip mining for quartzites in the Wisniowka Duza and Podwisniowka open pits, and (iii) evaluate the potential impact of mining and processing effluents on the quality of rivers. PMID- 27667332 TI - A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly. AB - BACKGROUND: Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. METHODS: A total of 370 healthy participants (?65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45MUg HA antigen/strain administered intradermally (ID) by MicronJet600TM microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal VTM (Janssen) and MF59 adjuvanted FluadTM (Novartis) administered IM and IntanzaTM (Sanofi Pasteur) administered ID via SoluviaTM prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. RESULTS: Intradermal delivery of virosomal vaccine using MicronJet600TM resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal VTM administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45MUg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ?1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). CONCLUSIONS: Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45MUg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15MUg commercial presentation. All treatments were generally safe and well tolerated. PMID- 27667335 TI - Time to go wireless? A 15-year single institution experience of radioisotope occult lesion localisation (ROLL) for impalpable breast lesions. AB - INTRODUCTION: Wire guided localisation (WGL) is the standard localisation technique for impalpable breast lesions. Radio-guided occult lesion localisation (ROLL) has been proposed as an alternative. We have been performing ROLL for therapeutic wide local excisions (WLE) and diagnostic excision biopsies (DEB) for the last 15 years. We present the largest reported consecutive series of ROLL excisions to date. PATIENTS AND METHODS: One thousand thirty nine consecutive patients who underwent ROLL for impalpable breast lesions were identified from a prospectively collected database. 673 patients underwent WLE and 366 patients underwent DEB. Data were analysed from proformas completed at the time of the procedure by the radiologist and operating surgeon. These data were supplemented with an analysis of patient electronic records including specimen radiograph and histopathology reports. RESULTS: 99.1% of ROLL WLE revealed histological diagnoses of invasive cancer or DCIS. 98.7% of radiological abnormalities were identified on WLE post-excision radiographs (97.5% following DEB). Complete excision was recorded in 79.0% of the WLE patients following histological evaluation. 31.7% of DEB cases were pathologically upgraded to a malignant diagnosis. The presence of microcalcification, preoperative underestimation of the lesion size and symptomatic referral predisposed to incomplete excision status. DISCUSSION: ROLL is a safe and effective technique to localise impalpable breast lesions. In addition ROLL has potential technical and logistic advantages over WGL. PMID- 27667336 TI - The Role of Endoproteolytic Processing in Neurodegeneration. AB - Endoproteolysis is a normal post-translational process in the eukaryotic cell that plays a role in protein evolution allowing protein catabolism and the generation of amino acids. Endoproteolytic cleavage regulates many crucial cellular processes including the activity of many proteins, their protein-protein interactions and the amplification of cell signals. Not surprisingly, disruption or alternation of endoproteolytic cleavage may be the root cause of many human diseases such as Alzheimer's disease, Huntington's disease and prion diseases. Most neurodegenerative diseases (ND) are caused by the build-up of misfolded proteins and the promotion of aggregation events. A common event that occurs in these ND is the alteration of endoproteolytic cleavage due to genetic mutations of the associated-proteases or target substrate. Endoproteolytic cleavage resulting in protein truncation has significant effects on the structure and function of a protein representing a common feature of ND. In this review, we will discuss the endoproteolytic cleavage events that lead to ND, namely Alzheimer's disease, Huntington's disease and prion diseases. PMID- 27667334 TI - Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo-electron microscopy. AB - The tremendous pandemic potential of coronaviruses was demonstrated twice in the last 15 years by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. Despite their biomedical importance, coronavirus S glycoproteins have proven difficult targets for structural characterization, precluding high-resolution studies of the biologically relevant trimer. Recent technological developments in single particle cryo-electron microscopy allowed us to determine the first structure of a coronavirus S glycoprotein trimer which provided a framework to understand the mechanisms of viral entry and suggested potential inhibition strategies for this family of viruses. Here, we describe the key factors that enabled this breakthrough. PMID- 27667337 TI - Why are behavioral and immune traits linked? AB - Through behavior, animals interact with a world where parasites abound. It is easy to understand how behavioral traits can thus have a differential effect on pathogen exposure. Harder to understand is why we observe behavioral traits to be linked to immune defense traits. Is variation in immune traits a consequence of behavior-induced variation in immunological experiences? Or is variation in behavioral traits a function of immune capabilities? Is our immune system a much bigger driver of personality than anticipated? In this review, I provide examples of how behavioral and immune traits co-vary. I then explore the different routes linking behavioral and immune traits, emphasizing on the physiological/hormonal mechanisms that could lead to immune control of behavior. Finally, I discuss why we should aim at understanding more about the mechanisms connecting these phenotypic traits. PMID- 27667338 TI - Do active patients seek higher quality prenatal care?: A panel data analysis from Nairobi, Kenya. AB - Despite poverty and limited access to health care, evidence is growing that patients in low-income countries are taking a more active role in their selection of health care providers. Urban areas such as Nairobi, Kenya offer a rich context for studying these "active" patients because of the large number of heterogeneous providers available. We use a unique panel dataset from 2015 in which 402 pregnant women from peri-urban (the "slums" of) Nairobi, Kenya were interviewed three times over the course of their pregnancy and delivery, allowing us to follow women's care decisions and their perceptions of the quality of care they received. We define active antenatal care (ANC) patients as those women who switch ANC providers and explore the prevalence, characteristics and care-seeking behavior of these patients. We analyze whether active ANC patients appear to be seeking out higher quality facilities and whether they are more satisfied with their care. Women in our sample visit over 150 different public and private ANC facilities. Active patients are more educated and more likely to have high risk pregnancies, but have otherwise similar characteristics to non-active patients. We find that active patients are increasingly likely to pay for private care (despite public care being free) and to receive a higher quality of care over the course of their pregnancy. We find that active patients appear more satisfied with their care over the course of pregnancy, as they are increasingly likely to choose to deliver at the facility providing their ANC. PMID- 27667339 TI - Gun violence in Americans' social network during their lifetime. AB - INTRODUCTION: The overall burden of gun violence death and injury in the US is now well understood. However, no study has shown the extent to which gun violence is associated with the individual lives of Americans. METHODS: We used fatal and non-fatal gun injury rates in 2013 from Centers for Disease Control and Prevention's Web-based Injury Statistics Query and Reporting System (WISQARS) and generally accepted estimates about the size of an American's social network to determine the likelihood that any given person will know someone in their personal social network who is a victim of gun violence during their lifetime. We derived estimates in the overall population and among racial/ethnic groups and by gun-injury intent. RESULTS: The likelihood of knowing a gun violence victim within any given personal network over a lifetime is 99.85% (99.8% to 99.9%). The likelihood among non-Hispanic white, black, Hispanic and other race Americans were 97.1%, 99.9%, 99.5% and 88.9% respectively. CONCLUSION: Nearly all Americans of all racial/ethnic groups are likely to know a victim of gun violence in their social network during their lifetime. PMID- 27667340 TI - The Institute of Medicine Report on the Future of Nursing: Where Are We 5 Years Later? PMID- 27667341 TI - Letter to the Editor. PMID- 27667342 TI - Letter to the Editor. PMID- 27667343 TI - A Quality Improvement Project: Using the STOP-BANG Tool in a Military Population to Improve Equity in Preoperative Screening. AB - BACKGROUND: The lack of a preoperative screening tool to detect obstructive sleep apnea (OSA) may lead to an increase in postoperative complications. AIM: The aim of the study was to implement a prescreening tool to identify diagnosed or undiagnosed OSA before a surgical procedure. SETTING: The study was conducted in the surgical admission center and postanesthesia care unit at a military treatment facility in Hawaii. PARTICIPANTS: Participants of the study included military personnel, military family members, veterans, and veteran beneficiaries. METHODS: The STOP-BANG (snore/tired/obstruction/pressure-body mass index/age/neck/gender) tool was used between April and June 2013 to identify and stratify 1,625 patients into low-risk, intermediate-risk, high-risk, and known OSA categories. RESULTS: The STOP-BANG tool confirmed the diagnosed OSA rate to be 13.48%, and increased at-risk OSA detection by 24.69%. Hawaiians/Pacific Islanders were more frequently found to be at risk with known OSA, likely to have complications, and be transferred to PACU 23-hour extended stay compared to other races and intermediate-risk and high-risk categories. CONCLUSION: The STOP-BANG tool identified and stratified surgical patients at risk for OSA and standardized OSA assessments. PMID- 27667344 TI - Correlational Study of Sleep Apnea Patient Characteristics With Discharge Locations. AB - PURPOSE: To determine if a correlation exists between OSA patient characteristics and the PACU discharge location; and the characteristics of the patients at-risk for low saturation levels, increased number of desaturations, and longer length of stay in the PACU. DESIGN: Retrospective, correlational study design. METHOD: Chart review of OSA patients >= 18 years old. Correlational analysis was performed between 15 high risk patient variables and the PACU discharge disposition: home or monitored bed. Complications resulting in monitored bed admission were reviewed. FINDINGS: 153 patients' charts were reviewed. The results showed that age>60, ASA classification, anesthesia type and narcotics use in the PACU were significantly correlated (p<=.05) with a patient's discharge disposition. DISCUSSION: The findings are consistent with other OSA research except BMI was not significant in this study. CONCLUSION: The results highlighted areas for future research and implications for clinical practice that would enable the perioperative care team to deliver safe care based on evidence. PMID- 27667345 TI - Implementing Capnography in the PACU and Beyond. AB - The potential risk of adverse effects from hypoventilation due to intravenous and/or intrathecal narcotic administration was recognized. Sauk Prairie Memorial Hospital and Clinics understood the limitations with the use of pulse oximetry and respiratory assessment in detecting adequate ventilation. Evidence has shown that capnography is the best indicator of respiratory depression. This article describes the implementation of monitoring program for high risk patients. Early recognition of respiratory depression via capnography has enabled Sauk Prairie Memorial Hospital to safely care for patients having intravenous and intrathecal narcotics. PMID- 27667346 TI - Nursing Management of Delirium in the Postanesthesia Care Unit and Intensive Care Unit. AB - PURPOSE: The purpose of the study was to examine nurses' approaches to care of patients with postoperative delirium in the postanesthesia care unit and intensive care unit. DESIGN: A descriptive survey design was used. METHODS: Eighty-seven nurses who have been working at a Training and Research Hospital in Erzurum, east of Turkey, were enrolled in this study between October 1 and November 20, 2012. FINDINGS: 83.9% of the nurses reported that they had given pharmacologic therapy for pain management in delirium patients, 39.1% massage, 31.0% rhythmic breathing exercise, and 26.4% music therapy. 90.8% of nurses also stated that they reduced noise and lighting at night to ensure normal sleep pattern. CONCLUSIONS: Nurses need to be supported to take part in courses, conferences, and training seminars. A standard data tool or scale needs to be used to assess delirium routinely in all patients admitted. PMID- 27667347 TI - How the Nurse Anesthetist Decides to Manage Perioperative Fluid Status. AB - PURPOSE: To determine the factors that affect how nurse anesthetists in a county in Sweden decide how to manage perioperative fluid status. DESIGN: A cross sectional qualitative study was conducted at two surgical wards in a county hospital. METHODS: Sixteen nurse anesthetists were interviewed to explore how nurse anesthetists assess patients' intraoperative fluid requirements and the subsequent measures adopted. FINDING: Three categories emerged through content analysis: clinical criteria and the thought process that drives decision making, interdependence in decision making, and uncertainty in decision making. CONCLUSIONS: This study revealed differences with regard to fluid management among nurse anesthetists in a county in Sweden. For the assessments and subsequent measures that are carried out to ensure optimal fluid therapy, more research is needed to provide evidence, and evidence-based guidelines need to be developed in Sweden. PMID- 27667348 TI - Effects of Enhanced Family Visitation in Postanesthesia Services. AB - PURPOSE: The purpose of this project was to assess the impact of an enhanced postanesthesia unit (PACU) family visitation program on surgical services staff. DESIGN: This project was a cross-sectional study using a mixed methods approach. METHODS: A survey, including scaled and qualitative items, was administered to surgical services personnel. FINDINGS: A significant positive change occurred in respondents' feelings of comfort when providing emotional support to family members, and 2013 respondents agreed more often than earlier respondents with the notion that family members should have the option to visit in the PACU. Qualitative data showed continuing concerns with space, privacy, and interference with patient care. CONCLUSIONS: Implementation of enhanced visiting policies in the PACU is associated with positive changes in staff attitudes toward family visitation and no diminishment of staff commitment to family support generally, but barriers to family visitation are persistent and substantial. PMID- 27667349 TI - Perioperative Patient Advocacy: An Integrative Review. AB - PURPOSE: The purpose of this review was to identify the characteristics and consequences of perioperative patient advocacy. DESIGN: An integrative review method was employed. METHODS: A database search to identify peer-reviewed articles that focused on perioperative patient advocacy was conducted in PubMed and CINAHL, followed by a manual search for additional articles. Studies were selected if they reported original empirical research findings with regard to perioperative patient advocacy. The data abstraction and synthesis were achieved with an inductive qualitative content analysis. FINDING: The analysis resulted in seven categories, two subthemes, and one main theme. The main theme, "Doing good for another human being-a balancing act between philanthropy and personal gratification," was the core of perioperative patient advocacy. CONCLUSION: Perioperative patient advocacy is part of the professional role of the perioperative nurse, and it affects the perioperative nurse emotionally. This advocacy shares similarities with descriptions of patient advocacy in general nursing. PMID- 27667350 TI - Ambulatory Surgery and Obstructive Sleep Apnea-A Challenge and Opportunity for Patient Health Teaching. PMID- 27667351 TI - Evidence Into Practice: Disseminating an Evidence-Based Practice Project as a Poster. PMID- 27667352 TI - Postoperative Pain Management: Clinical Practice Guidelines. PMID- 27667354 TI - A Race to the Polls: One in 45. PMID- 27667353 TI - Therapeutic Play Intervention. PMID- 27667355 TI - Body Image in Transmen: Multidimensional Measurement and the Effects of Mastectomy. AB - INTRODUCTION: Transmen are generally dissatisfied with their breasts and often opt for mastectomy. However, little is known about the specific effects of this procedure on this group's body image. AIM: To prospectively assess the effect of mastectomy on the body image of transmen, including cognitive, emotional, and behavioral aspects. METHODS: During a 10-month period, all transmen applying for mastectomy were invited to participate in this study. The 33 participants completed assessments preoperatively and at least 6 months postoperatively. MAIN OUTCOME MEASURES: Participants were surveyed on body satisfaction (Body Image Scale for Transsexuals), body attitudes (Multidimensional Body-Self Relations Questionnaire), appearance schemas (Appearance Schemas Inventory), situational bodily feelings (Situational Inventory of Body Image Dysphoria), body image related quality of life (Body Image Quality of Life Inventory), and self-esteem (Rosenberg Self-Esteem Scale). Control values were retrieved from the literature and a college sample. RESULTS: Before surgery, transmen reported less positive body attitudes and satisfaction, a lower self-esteem and body image-related quality of life compared with cisgender men and women. Mastectomy improved body satisfaction most strongly, although respondents reported improvements in all domains (eg, decreased dysphoria when looking in the mirror and improved feelings of self-worth). Most outcome measurements were strongly correlated. CONCLUSION: Mastectomy improves body image beyond satisfaction with chest appearance alone. Body satisfaction and feelings of "passing" in social situations are associated with a higher quality of life and self-esteem. PMID- 27667356 TI - Clitorally Stimulated Orgasms Are Associated With Better Control of Sexual Desire, and Not Associated With Depression or Anxiety, Compared With Vaginally Stimulated Orgasms. AB - INTRODUCTION: Most women report that clitoral stimulation is an integral aspect of their orgasm experience. Thus, recent claims that vaginal stimulation and vaginally generated orgasms are superior to clitoral stimulation and clitorally generated orgasms pathologize most women and maintain a clitoral vs vaginal dichotomy that might not accurately reflect the complexity of women's sexual experience. AIM: To have women report on their experienced source of orgasm, including combinations of vaginal and clitoral stimulation, the solo or partnered context of the stimulation, and the intensity of the orgasms from different sources and to predict indicators of mental health and sexual health using the orgasm source. METHODS: Eighty-eight women 18 to 53 years old answered detailed questions about their usual and recent orgasm experiences, sexual history, depression, and anxiety. Then, they viewed a series of neutral and sexual films. They were instructed to increase or decrease their sexual arousal or respond "as usual" to the sexual films. They reported their sexual arousal after each film. MAIN OUTCOME MEASURES: Outcomes assessed included mental health (depression and anxiety) and sexual health (orgasm quality, ability to regulate sexual response to sex films). Reported sexual arousal was analyzed for the regulation task. RESULTS: Most women (64%) reported that clitoral and vaginal stimulation contributed to their usual method of reaching orgasm. Women who reported that clitoral stimulation was primarily responsible for their orgasm reported a higher desire to self-stimulate and demonstrated greater control over their self reported sexual arousal. The primary stimulation site for orgasm was unrelated to measurements of depression or anxiety despite sufficient statistical power. CONCLUSION: Most women reported that clitoral and vaginal stimulation is important in orgasm. Women experience orgasms in many varied patterns, a complexity that is often ignored by current methods of assessing orgasm source. The reported source of orgasm was unrelated to orgasm intensity, overall sex-life satisfaction, sexual distress, depression, or anxiety. Women who reported primarily stimulating their clitoris to reach orgasm reported higher trait sexual drive and higher sexual arousal to visual sexual stimulation and were better able to increase their sexual arousal to visual sexual stimulation when instructed than women who reported orgasms primarily from vaginal sources. PMID- 27667357 TI - Angiogenin elevates the invasive potential of squamous cell lung carcinoma cells through epithelial-mesenchymal transition. AB - Squamous cell carcinoma of the lung is one of the most aggressive cancers, and its aggressiveness is in part due to its intrinsic high rate of metastasis. Moreover, the process of epithelial-mesenchymal transition (EMT) appears to be involved in these neoplastic processes. Furthermore, EMT-type cells share many biological characteristics with the function of angiogenin (ANG) in squamous cell lung carcinoma. We conducted immunohistochemical analysis to detect the expression of ANG, E-cadherin, vimentin, N-cadherin, beta-catenin and TGF-beta1 in 60 cases of squamous cell lung carcinoma tissues. Western blot analysis was adopted to detect the protein expression levels of ANG and EMT markers. The effects of ANG on proliferation, migration and invasion of squamous cell lung carcinoma cells was analyzed by Cell Counting Kit-8, scratch assay and Transwell invasion chamber in order to reveal the role of ANG in the process of EMT in squamous cell lung carcinoma. The results revealed that ANG was aberrantly expressed in the squamous cell lung carcinoma specimens and was closely correlated with the differentiation of the cell lines. The expression of ANG was also significantly associated with metastasis and the stage of the squamous cell lung carcinoma cases. In addition, we validated that ANG influenced the expression of vimentin, E-cadherin, N-cadherin, beta-catenin and TGF-beta1 in SK MES-1 cells. Most importantly, overexpression of ANG enhanced the migration and invasion of SK-MES-1 cells, while knockdown resulted in opposite effects. In the present study, we found that ANG plays an important role in EMT in squamous cell lung carcinoma and may be a valuable therapeutic target for squamous cell lung carcinoma. PMID- 27667358 TI - Tracing the neural basis of auditory entrainment. AB - Neurons in the auditory cortex synchronize their responses to temporal regularities in sound input. This coupling or "entrainment" is thought to facilitate beat extraction and rhythm perception in temporally structured sounds, such as music. As a consequence of such entrainment, the auditory cortex responds to an omitted (silent) sound in a regular sequence. Although previous studies suggest that the auditory brainstem frequency-following response (FFR) exhibits some of the beat-related effects found in the cortex, it is unknown whether omissions of sounds evoke a brainstem response. We simultaneously recorded cortical and brainstem responses to isochronous and irregular sequences of consonant-vowel syllable /da/ that contained sporadic omissions. The auditory cortex responded strongly to omissions, but we found no evidence of evoked responses to omitted stimuli from the auditory brainstem. However, auditory brainstem responses in the isochronous sound sequence were more consistent across trials than in the irregular sequence. These results indicate that the auditory brainstem faithfully encodes short-term acoustic properties of a stimulus and is sensitive to sequence regularity, but does not entrain to isochronous sequences sufficiently to generate overt omission responses, even for sequences that evoke such responses in the cortex. These findings add to our understanding of the processing of sound regularities, which is an important aspect of human cognitive abilities like rhythm, music and speech perception. PMID- 27667359 TI - An unanticipated question. PMID- 27667360 TI - SMC1A promotes growth and migration of prostate cancer in vitro and in vivo. AB - Structural maintenance of chromosome 1 alpha (SMC1A) gene has been reported to be related to tumor development in some types of human cancers. However, the misregulation of SMC1A and its functions in castration-resistant prostate cancer (CRPC) have not been well understood. In the present study, we found that SMC1A was elevated in androgen-independent PCa cell lines PC-3 and DU-145 compared to androgen sensitive LNCap and 22RV1 cells by qPCR and western blot assay. Knockdown of SMC1A inhibited cell growth, colony formation and cell migration abilities of PC-3 and DU145 cells by MTT, colony formation and transwell assays, and affected cell cycle progression in PC-3 and DU145 cells by flow cytometry. Moreover, SMC1A knockdown significantly reduced tumor growth in vivo in a nude mouse model. Additionally, we also found that the expression of SMC1A gene was higher in prostate cancer tissues than in the adjacent normal tissues by immunohistochemical staining, and was positively correlated to tumor metastasis and recurrence by Oncomine database mining. Taken together, the present study indicates that SMC1A may play an important role in malignant transformation of PCa under conditions of androgen deprivation and act as a new target for PCa diagnosis and treatment. PMID- 27667361 TI - Dopa-responsive dystonia or early-onset Parkinson disease - Genotype-phenotype correlation. AB - OBJECTIVE: Dopa-responsive dystonia (DRD) is a rare form of hereditary movement disorder with onset in childhood, characterized by gait difficulties due to postural dystonia with marked improvement after low doses of levodopa. Mutations in the GCH1 gene are the most common cause of DRD, however, in some cases when the disease is associated with parkinsonism mutations in the PARK2 gene may be identified. The aim of this study was to analyze and compare genotype-phenotype correlation. MATERIAL/PARTICIPANTS: Four families with inter- and intrafamilial variability of progressive gait dysfunction due to lower limb dystonia occurring in childhood or adolescence were included in the analysis. METHODS: General and neurological examination was performed for all affected family members and asymptomatic mutation carriers. The molecular analysis encompassed GCH1 and PARK2 genes. RESULTS: All probands were clinically diagnosed with DRD. The molecular analysis revealed, however, that the dopa-responsive dystonia phenotype was caused by a mutation in the GCH1 gene in three families and in the PARK2 gene in one family. Obtained results allowed to establish the final diagnosis for all families as DYT5a or early-onset Parkinson disease (EO-PD). CONCLUSIONS: Reported cases confirm that the DRD phenotype may have heterogeneous genetic background and may be caused by point mutations or rearrangements in the GCH1 gene as well as in the PARK2 gene. Differential diagnosis and genetic tests covering the analysis of genes causative for DRD and EO-PD should be obligatory in both disorders diagnostics as DRD, mainly adolescent onset dystonia, may be associated with parkinsonism. PMID- 27667362 TI - Serotypes, virulence profiles and stx subtypes of Shigatoxigenic Escherichia coli isolated from chicken derived products. AB - Shigatoxigenic Escherichia coli (STEC) is a foodborne pathogen that causes hemolytic uremic syndrome (HUS) and the consumption of chicken products has been related to some HUS cases. We performed a non-selective isolation and characterization of STEC strains from retail chicken products. STEC isolates were characterized according to the presence of stx1, stx2, eae, saa and ehxA; stx subtypes and serotypes. Most of them carried stx2, showing subtypes associated with severe human disease. Although reported in other avian species, the stx2f subtype was not detected. The isolates corresponded to different serotypes and some of them, such as O22:H8, O113:H21, O130:H11, O171:H2 and O178:H19, have also been identified among STEC isolated from patients suffering from diarrhea, hemorrhagic colitis, HUS, as well as from cattle. Considering the virulence profiles and serotypes identified, our results indicate that raw chicken products, especially hamburgers sold at butcheries, can be vehicles for high-risk STEC strains. PMID- 27667363 TI - Multi-omics Quantification of Species Variation of Escherichia coli Links Molecular Features with Strain Phenotypes. AB - Escherichia coli strains are widely used in academic research and biotechnology. New technologies for quantifying strain-specific differences and their underlying contributing factors promise greater understanding of how these differences significantly impact physiology, synthetic biology, metabolic engineering, and process design. Here, we quantified strain-specific differences in seven widely used strains of E. coli (BL21, C, Crooks, DH5a, K-12 MG1655, K-12 W3110, and W) using genomics, phenomics, transcriptomics, and genome-scale modeling. Metabolic physiology and gene expression varied widely with downstream implications for productivity, product yield, and titer. These differences could be linked to differential regulatory structure. Analyzing high-flux reactions and expression of encoding genes resulted in a correlated and quantitative link between these sets, with strain-specific caveats. Integrated modeling revealed that certain strains are better suited to produce given compounds or express desired constructs considering native expression states of pathways that enable high production phenotypes. This study yields a framework for quantitatively comparing strains in a species with implications for strain selection. PMID- 27667364 TI - Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration. AB - Increased expression of vimentin intermediate filaments (VIFs) enhances directed cell migration, but the mechanism behind VIFs' effect on motility is not understood. VIFs interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here, we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of retinal pigment epithelial cells. By genome editing, we fluorescently labeled endogenous vimentin and alpha-tubulin, and we developed computational image analysis to delineate architecture and interactions of the two networks. Our results show that VIFs assemble an ultrastructural copy of the previously polarized microtubule network. Because the VIF network is long-lived compared to the microtubule network, VIFs template future microtubule growth along previous microtubule tracks, thus providing a feedback mechanism that maintains cell polarity. VIF knockdown prevents cells from polarizing and migrating properly during wound healing. We suggest that VIFs' templating function establishes a memory in microtubule organization that enhances persistence in cell polarization in general and migration in particular. PMID- 27667365 TI - A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure. AB - Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes. PMID- 27667367 TI - EASL Recommendations on Treatment of Hepatitis C 2016. PMID- 27667366 TI - Highly Multiplexed Quantitative Mass Spectrometry Analysis of Ubiquitylomes. AB - System-wide quantitative analysis of ubiquitylomes has proven to be a valuable tool for elucidating targets and mechanisms of the ubiquitin-driven signaling systems, as well as gaining insights into neurodegenerative diseases and cancer. Current mass spectrometry methods for ubiquitylome detection require large amounts of starting material and rely on stochastic data collection to increase replicate analyses. We describe a method compatible with cell line and tissue samples for large-scale quantification of 5,000-9,000 ubiquitylation forms across ten samples simultaneously. Using this method, we reveal site-specific ubiquitylation in mammalian brain and liver tissues, as well as in cancer cells undergoing proteasome inhibition. To demonstrate the power of the approach for signal-dependent ubiquitylation, we examined protein and ubiquitylation dynamics for mitochondria undergoing PARKIN- and PINK1-dependent mitophagy. This analysis revealed the largest collection of PARKIN- and PINK1-dependent ubiquitylation targets to date in a single experiment, and it also revealed a subset of proteins recruited to the mitochondria during mitophagy. PMID- 27667368 TI - The value of counting WHO-defined cardiovascular risk factors for death and disability in a national sample of adults with psychosis. AB - OBJECTIVE: This study explored the prevalence and associations of eight WHO defined CVD risk factors for death and disability in people with psychosis. METHOD: The study included 1156 people aged 18-64years, diagnosed with psychosis. The 2009 World Health Organisation (WHO) Global Health Risks Report was used as a framework to determine the prevalence and number of eight key risk factors for cardiovascular disease (CVD) in men and women with psychosis. Differences in the number and type of risk factors by age and gender were investigated. Multi predictor analysis was performed to identify associations between demographic factors, psychiatric diagnosis and accumulative CVD risk factors. RESULTS: Women had fewer CVD risk factors than men. The number of risk factors significantly decreased in association with single marital status, current employment and significantly increased with earning a higher income. People aged 35-49years and 50-64years had an average of 4 risk factors (SD 1.38 and 1.30); people aged 18 34years had an average of 3 risk factors (SD 1.30). Mean risk factors were higher in the middle age and older age groups (35-49years and 50-64years) compared with the younger age group (18-34years) (p<0.0001). Overweight/obesity, hypertension, high blood glucose/diabetes and high cholesterol were significantly more prevalent in older men and women. CONCLUSION: People with psychosis have a high prevalence of individual and aggregate CVD risks. These were more common in men and rose with age, implying the necessity of close clinical monitoring. The most common risk factors should be targeted by lifestyle interventions. PMID- 27667370 TI - Primary Outcomes Reporting in Trials (PORTal): a systematic review of inadequate reporting in pediatric randomized controlled trials. AB - OBJECTIVE: Conduct a systematic review of pediatric randomized controlled trials (RCTs) published in high-impact journals to assess the reporting of primary outcomes and the psychometric properties of their measures. STUDY DESIGN AND SETTING: Systematic review with screening and simultaneous data extraction conducted by two independent reviewers. Electronic searches of six general medicine and four pediatric journals were conducted in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. RCTs of a single phase/step in a single publication, published in English between 2000 and 2010 with participants less than 21 years of age were included. RESULTS: A random sample of 20% (n = 445) of 2,229 initial references was screened and 206 (46%) met inclusion criteria. Half (48.5%) of included studies reported a singular primary outcome, 27% did not identify any primary outcome, and 24% identified multiple primary outcomes (range 2-20). Twenty-one trials used an instrument to measure their primary outcome, but only 7 (33%) reported its psychometric properties. CONCLUSION: Pediatric trials published in top medical journals have inadequate reporting of their primary outcomes and the psychometric properties of their outcome measures. Whether the issue is one of poor reporting and/or poor validation will be further investigated. PMID- 27667369 TI - Supported employment and education in comprehensive, integrated care for first episode psychosis: Effects on work, school, and disability income. AB - BACKGROUND: Participation in work and school are central objectives for first episode psychosis (FEP) programs, but evidence effectiveness has been mixed in studies not focused exclusively on supported employment and education (SEE). Requirements for current motivation to work or go to school limit the generalizability of such studies. METHODS: FEP participants (N=404) at thirty four community treatment clinics participated in a cluster randomized trial that compared usual Community Care (CC) to NAVIGATE, a comprehensive, team-based treatment program that included >=5h of SEE services per week, , grounded in many of the principles of the Individual Placement and Support model of supported employment combined with supported education services. All study participants were offered SEE regardless of their initial interest in work or school. Monthly assessments over 24months recorded days of employment and attendance at school, days of participation in SEE, and both employment and public support income (including disability income). General Estimation Equation models were used to compare CC and NAVIGATE on work and school participation, employment and public support income, and the mediating effect of receiving >=3 SEE visits on these outcomes. RESULTS: NAVIGATE treatment was associated with a greater increase in participation in work or school (p=0.0486) and this difference appeared to be mediated by SEE. No group differences were observed in earnings or public support payments. CONCLUSION: A comprehensive, team-based FEP treatment approach was associated with greater improvement in work or school participation, and this effect appears to be mediated, in part, by participation in SEE. PMID- 27667371 TI - Crystalline keratopathy due to intravenous immunoglobulin in a 12-year-old girl with Kawasaki disease. AB - Kawasaki disease (KD) is an acute, self-limiting, medium-vessel vasculitis that occurs predominantly in young children. The treatment of KD consists of intravenous immunoglobulin (IVIG) along with aspirin and, in IVIG-resistant cases, corticosteroids. Crystalline keratopathy with corneal deposition of the immunoglobulin is a rare complication of IVIG therapy. We report the case of a 12 year-old girl who received IVIG for KD and developed visual complaints, which were attributable to crystalline keratopathy and corneal edema. Cessation of IVIG and treatment with topical and systemic corticosteroids reversed the finding. At final follow-up, vision in both eyes was normal. PMID- 27667372 TI - Surgical correction of an inferiorly displaced lateral rectus with equatorial myopexy. AB - Orbital connective tissue normally loses strength and rigidity during aging. The lateral rectus pulley that surrounds and directs the lateral rectus path has the flimsiest support and can sag too far inferiorly, resulting in significantly reduced abducting force and secondary esotropia. This displacement is worsened by a weakened lateral rectus-superior rectus band from high myopia. Augmented medial rectus recessions can correct the esotropia, but long-term results may be less predictable because the underlying anatomic abnormality, the sagging lateral rectus muscle, has not been addressed. Lateral rectus equatorial myopexy is a straightforward technique that uses a permanent scleral suture to fixate the posterior lateral rectus belly into its correct anatomic position. The response to surgery depends on the magnitude of lateral rectus sag and is somewhat self titrating-more sag correlates with both larger distance esotropia and thus larger corrections from lateral rectus equatorial myopexy alone-but larger deviations often require repositioning of muscle insertions to compensate for secondary changes to muscle lengths and tension. PMID- 27667373 TI - Hepatitis C virus resistance to broadly neutralizing antibodies measured using replication-competent virus and pseudoparticles. AB - A better understanding of natural variation in neutralization resistance and fitness of diverse hepatitis C virus (HCV) envelope (E1E2) variants will be critical to guide rational development of an HCV vaccine. This work has been hindered by inadequate genetic diversity in viral panels and by a lack of standardization of HCV entry assays. Neutralization assays generally use lentiviral pseudoparticles expressing HCV envelope proteins (HCVpp) or chimeric full-length viruses that are replication competent in cell culture (HCVcc). There have been few systematic comparisons of specific infectivities of E1E2-matched HCVcc and HCVpp, and to our knowledge, neutralization of E1E2-matched HCVpp and HCVcc has never been compared using a diverse panel of human broadly neutralizing monoclonal antibodies (bNAbs) targeting distinct epitopes. Here, we describe an efficient method for introduction of naturally occurring E1E2 genes into a full length HCV genome, producing replication-competent chimeric HCVcc. We generated diverse panels of E1E2-matched HCVcc and HCVpp and measured the entry-mediating fitness of E1E2 variants using the two systems. We also compared neutralization of E1E2-matched HCVcc and HCVpp by a diverse panel of human bNAbs targeting epitopes across E1E2. We found no correlation between specific infectivities of E1E2-matched HCVcc versus HCVpp, but found a very strong positive correlation between relative neutralization resistance of these same E1E2-matched HCVcc and HCVpp variants. These results suggest that quantitative comparisons of neutralization resistance of E1E2 variants can be made with confidence using either HCVcc or HCVpp, allowing the use of either or both systems to maximize diversity of neutralization panels. PMID- 27667375 TI - A Decade of Progress in Regional ST-Segment Elevation Myocardial Infarction Systems of Care: A Tale of Two Cities. AB - Over the past 20 years, care for patients with ST-elevation myocardial infarction (STEMI) has rapidly evolved, not just in terms of how patients are treated, but where patients are treated. The advent of regional STEMI systems of care has decreased the number of "eligible but untreated" patients while improving access to primary percutaneous coronary intervention for patients. These regional STEMI systems of care have consistently demonstrated that rapid transport of STEMI patients is safe and effective, and have shown marked improvements in a variety of clinical outcomes. However, no two STEMI systems are alike, and each must be tailored to the unique geographic, political, and socioeconomic challenges of the region. This article takes an in-depth look at two of the earliest STEMI systems within the United States: the Minneapolis Heart Institute and the Los Angeles County STEMI receiving network. PMID- 27667374 TI - Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors. AB - Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging. PMID- 27667376 TI - A Closer Look at Fractional Flow Reserve in Complex Anatomic Subsets: Left Main Disease, Bifurcation Lesions, and Saphenous Vein Grafts. AB - Fractional flow reserve (FFR) is a well-validated tool for determining the functional significance of a coronary artery stenosis, facilitating clinical decisions regarding the need for revascularization. FFR-guided revascularization improves clinical and economic outcomes. However, its application remains challenging in certain complex anatomic subsets, including left main coronary artery stenosis, bifurcation disease, and saphenous vein graft disease. This article reviews recent data supporting the use of FFR in these complex anatomic subsets. PMID- 27667377 TI - Emerging Treatments for Heterozygous and Homozygous Familial Hypercholesterolemia. AB - Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder marked by extremely high low-density lipoprotein (LDL) cholesterol levels and concomitant premature vascular disease. FH is caused by mutations that most commonly affect three genes integrally involved in the LDL receptor's ability to clear LDL particles from the circulation. Primary intervention efforts to lower LDL cholesterol have centered on therapies that upregulate the LDL receptor. Unfortunately, most patients are insufficiently responsive to traditional LDL lowering medications. This article focuses primarily on the clinical management of homozygous FH. PMID- 27667378 TI - The Role of Medical Therapy in Moderate to Severe Degenerative Mitral Regurgitation. AB - Mitral regurgitation (MR) is a common valvular disorder that has important health and economic consequences. Standardized guidelines exist regarding when and in whom to perform mitral valve surgery, but little information is available regarding medical treatment of MR. Many patients with moderate or severe MR do not meet criteria for surgery or are deemed to be at high risk for surgical therapy. We reviewed the available published data on medical therapy in the treatment of patients with primary MR. b-blockers and renin-angiotensin aldosterone system inhibitors had the strongest supporting evidence for providing beneficial effects. b-blockers appear to lessen MR, prevent deterioration of left ventricular function, and improve survival in asymptomatic patients with moderate to severe primary MR. Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy reduces MR, especially in asymptomatic patients. However, in the setting of hypertrophic cardiomyopathy or mitral valve prolapse, vasodilators can increase the severity of MR. To define the precise role of medical therapy, a larger randomized controlled trial is needed to confirm benefit and assess in which subsets of patients medical therapy is most useful. Medical therapy in some patients improves symptoms, lessens MR, and may delay the need for surgical intervention. PMID- 27667379 TI - A Review of the Clinical Subgroup Analyses From the RE-LY Trial. AB - Dabigatran was the first direct-acting oral anticoagulant approved by the US Food and Drug Administration for prevention of stroke and systemic embolism in people with atrial fibrillation, based on data from the Randomized Evaluation of Long Term Anticoagulation Therapy (RE-LY) trial. Over 18,000 patients with nonvalvular atrial fibrillation and a moderate-to-high risk of thromboembolic stroke were randomized to warfarin or dabigatran. With respect to the primary endpoints for efficacy and safety, dabigatran was superior to warfarin in the prevention of stroke and thromboembolism and noninferior with respect to major bleeding. Although unified by a common arrhythmia and a similar thromboembolic stroke risk, this large patient population is also significantly heterogeneous with respect to other demographics and comorbidities that raise important questions about the efficacy and safety of dabigatran in specific patient populations. Furthermore, there were significant differences between the warfarin and dabigatran groups with respect to several important secondary endpoints. Understanding the differences in outcomes between specific patient subgroups from the RE-LY trial can better inform the practicing clinician's ability to offer the best anticoagulation options to individual patients. PMID- 27667380 TI - Cardiovascular Effects of Altitude on Performance Athletes. AB - Altitude plays an important role in cardiovascular performance and training for athletes. Whether it is mountaineers, skiers, or sea-level athletes trying to gain an edge by training or living at increased altitude, there are many potential benefits and harms of such endeavors. Echocardiographic studies done on athletes at increased altitude have shown evidence for right ventricular dysfunction and pulmonary hypertension, but no change in left ventricular ejection fraction. In addition, 10% of athletes are susceptible to pulmonary hypertension and high-altitude pulmonary edema. Some studies suggest that echocardiography may be able to identify athletes susceptible to high-altitude pulmonary edema prior to competing or training at increased altitudes. Further research is needed on the long-term effects of altitude training, as repeated, transient episodes of pulmonary hypertension and right ventricular dysfunction may have long-term implications. Current literature suggests that performance athletes are not at higher risk for ventricular arrhythmias when training or competing at increased altitudes. For sea-level athletes, the optimal strategy for attaining the benefits while minimizing the harms of altitude training still needs to be clarified, although-for now-the "live high, train low" approach appears to have the most rationale. PMID- 27667381 TI - The Role of Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy. AB - Until recently, the only imaging technique for the diagnosis and management of hypertrophic cardiomyopathy (HCM) was two-dimensional echocardiography, and the use of cardiac magnetic resonance imaging (cMRI) was limited to patients with poor acoustic windows. Now, cMRI has gained an essential role in the diagnosis of HCM, providing superior visualization of myocardial hypertrophy-even in remote zones of the left ventricle-and visualization of subtle changes in thickness and contractility over time. The morphologic accuracy of cMRI allows for the differentiation of HCM from other pathologic conditions with hypertrophic phenotype. Moreover, cMRI sheds light on the in vivo fibrotic changes in cardiac ultrastructure, offering an important advantage in the understanding of pathologic mechanisms of the disease, allowing early identification, risk stratification, and timely therapeutic management. PMID- 27667382 TI - An Update From the California Chapter of the American College of Cardiology Board of Directors. PMID- 27667384 TI - Forty Years of Chest Pain: A Case Report and Contemporary Review of the Diagnostic and Therapeutic Options for Myocardial Bridging. AB - A 48-year-old woman with 40 years of intermittent squeezing chest pain presented with worsening symptoms. Results of an ambulatory electrocardiogram, echocardiogram, and exercise treadmill were unremarkable. Persistent symptoms prompted a computed tomography coronary angiogram (CTCA) that revealed mid-left anterior descending artery myocardial bridging (MB) that was not physiologically significant by exercise single-photon emission CT. Conservative treatment was pursued. Anatomic MB is prevalent in a large proportion of the general population and are increasingly identified by CTCA. The majority are benign, physiologically significant bridging is uncommon, but accelerated proximal atherosclerosis can occur. b-blockers and nondihydropyridine calcium-channel blockers are the primary treatment options, with surgical myomectomy, coronary artery bypass, and stenting reserved for patients refractory to medical therapy with demonstrable ischemia. Head-to-head evaluation of nonpharmacologic therapies is needed. Intracoronary techniques provide simultaneous anatomical and physiological assessment but CTCA fractional flow reserve and hybrid positron emission tomography with concomitant spatial imaging systems are evolving as noninvasive alternatives. PMID- 27667383 TI - Leading the Way: Cardiology and the Future of HealthTech Innovation. PMID- 27667385 TI - Vascular Complications of Percutaneous Transradial Cardiac Catheterization. AB - The percutaneous transradial approach for coronary angiography and percutaneous coronary intervention is increasing in the United States. Although its vascular safety profile is better than the traditional femoral approach, it is important to learn about potential complications. In this article, we present two cases of vascular complications, namely, pseudoaneurysm and radial artery occlusion, after transradial cardiac catheterization, along with a review of the relevant literature. PMID- 27667386 TI - Isolated Left Ventricular Noncompaction Cardiomyopathy: A Transient Disease? AB - Isolated left ventricular noncompaction is either a distinct cardiomyopathy or a morphologic trait shared by several different types of cardiomyopathies. Although there is no current gold standard for its diagnosis, cardiac imaging is the most commonly accepted modality. Described is a case of left ventricular noncompaction that resolved 2 years after the initial diagnosis. PMID- 27667387 TI - Reply to Letter to the Editor - The Definition of 'Urgent' in Australia and New Zealand Society of Cardiac and Thoracic Surgeons Database. PMID- 27667388 TI - Quantitative proteomics reveals ecological fitness cost of multi-herbicide resistant barnyardgrass (Echinochloa crus-galli L.). AB - : Barnyardgrass (Echinochloa crus-galli) is one of the top 15 herbicide-resistant weeds around the world that interferes with rice growth, resulting in major losses of rice yield. Thus, multi-herbicide resistance in barnyardgrass presents a major threat, with the underlying mechanisms that contribute to resistance requiring elucidation. In an attempt to characterize this multi-herbicide resistance at the proteomic level, comparative analysis of resistant and susceptible barnyardgrasses was performed using iTRAQ, both with and without quinclorac, bispyribac-sodium and penoxsulam herbicidal treatment. A total of 1342 protein species were identified from 2248 unique peptides by searching the UniProt database and conducting data analysis. Approximately 904 protein species with 4774 Gene Ontology (GO) terms were grouped into the categories of biological process, cellular component and molecular function. Among these, 688 protein species were annotated into 1583 KEGG pathways, with 980 protein species relating to metabolism and 93 relating to environmental information processing. A total of 292 protein species showed more than a 1.2-fold change in abundance in the resistant biotype relative to the susceptible biotype. Furthermore, herbicide treatment resulted in 157 protein species that showed more than a 1.2-fold change in the resistant biotype. Moreover, physiological analyses demonstrated an ecological fitness cost in the resistant biotype. SIGNIFICANCE: While some studies have shown a fitness cost to be associated with an altered ecological interaction, our understanding of the fitness costs associated with herbicide resistance are limited. Herein, physiological and proteomic analysis demonstrates herbicide resistance associated ecological fitness cost and potential mechanisms of herbicide-resistance in resistant biotypes of E. crus-galli. The results presented herein have revealed differences in ecological adaptation between resistant and susceptible biotypes in E. crus-galli and provide a fundamental basis enabling the development of new strategies for weed control. Lastly, this is the first large-scale proteomics study to examine herbicide stress responses in different barnyardgrass biotypes. PMID- 27667389 TI - On-column trypsin digestion coupled with LC-MS/MS for quantification of apolipoproteins. AB - : Apolipoproteins measured in plasma or serum are potential biomarkers for assessing metabolic irregularities that are associated with the development of cardiovascular disease (CVD). LC-MS/MS allows quantitative measurement of multiple apolipoproteins in the same sample run. However, the accuracy and precision of the LC-MS/MS measurement depends on the reproducibility of the enzymatic protein digestion step. With the application of an immobilized enzyme reactor (IMER), the reproducibility of the trypsin digestion can be controlled with high precision via flow rate, column volume and temperature. In this report, we demonstrate the application of an integrated IMER-LC-MS/MS platform for the simultaneous quantitative analysis of eight apolipoproteins. Using a dilution series of a characterized serum pool as calibrator, the method was validated by repeated analysis of pooled sera and individual serum samples with a wide range of lipid profiles, all showing intra-assay CV<4.4% and inter-assay CV<8%. In addition, the method was compared with traditional homogeneous digestion coupled LC-MS/MS for the quantification of apoA-I and apoB-100. Applied in large scale human population studies, this method can serve the translation of a wider panel of apolipoprotein biomarkers from research to clinical application. SIGNIFICANCE: Currently, the translation of apolipoprotein biomarkers to clinical application is impaired because of the high cost of large cohort studies using traditional single-analyte immunoassays. The application of on-line tryptic digestion coupled with LC-MS/MS analysis is an effective way to address this problem. In this work we demonstrate a high throughput, multiplexed, automated proteomics workflow for the simultaneous analysis of multiple proteins. PMID- 27667390 TI - Disease genetics: Under pressure - genetics of hypertension. PMID- 27667391 TI - Mobile elements: Putting the brakes on ageing. PMID- 27667392 TI - Dysregulation of GTPase IMAP family members in hepatocellular cancer. AB - Hepatocellular carcinoma (HCC) is one of the most life-threatening diseases in the world. Members of the GTPase of the immunity-associated protein (GIMAP) family are important in regulating apoptosis in cancer cells. However, the basic mechanism of GIMAP in HCC remains to be fully elucidated. The present study was performed to investigate the dysregulation of GIMAP family members in HCC. The techniques of polymerase chain reaction analysis, immunohistochemistry and ELISA were used to analyze the expression of GIMAP5 and GIMAP6 in HCC tissues, in matched noncancerous tissue samples, and in blood samples obtained from patients with HCC and healthy subjects. It was found that the mRNA expression levels of GIMAP5 and GIMAP6 were significantly downregulated in the HCC tumor samples, compared with the levels of expression in the matched non-tumor tissue samples. Similarly, the mRNA expression levels of GIMAP5 and GIMAP6 were also significantly downregulated in the blood samples from patients with HCC, compared with the expression levels in the blood from healthy subjects. At the protein level, it was found that the GIMAP5 and GIMAP6 proteins were expressed at lower levels in the tumor tissue samples, compared with the matched normal tissue samples, and their expression levels were also lower in the blood samples from patients with HCC, compared with the blood samples from the healthy subjects. These data, demonstrating the downregulation of the mRNA and protein expression levels of GIMAP5 and GIMAP6 in the tumor tissues and blood of patients with HCC, suggested the involvement of GIMAP5 and GIMAP6 in the pathogenesis of HCC, and indicate their possible use as diagnostic markers for HCC. PMID- 27667393 TI - A real-time study of the interaction of TBP with a TATA box-containing duplex identical to an ancestral or minor allele of human gene LEP or TPI. AB - It is known that only a single-nucleotide substitution (SNP: a single nucleotide polymorphism) in the sequence of a TATA box can influence the affinity of the interaction of TBP with the TATA box and contribute to the pathogenesis of complex hereditary human diseases and sometimes may be a cause of monogenic diseases (for instance, beta-thalassemia). In the present work, we studied the interaction of human TBP with a double-stranded oligodeoxyribonucleotide (ODN) 15 or 26 bp long identical to a TATA box of promoters of a real-life human gene, TPI or LEP, and labeled with fluorophores TAMRA and FAM. To analyze the interaction of TBP with a TATA box of an ancestral or minor allele (SNP in the TATA box) in real time, we used the stopped-flow method with detection of a Forster resonance energy transfer (FRET) signal. The nature of the resulting kinetic curves reflecting changes in the FRET signal (and therefore of DNA conformation during the interaction with TBP) pointed to a multistage mechanism of the formation of the TBP complex with the TATA-containing ODN. The results showed that with the increasing concentration and length of the ODN, heterogeneity of conformational changes (taking place during the first second of the interaction with TBP) in DNA also increases. In contrast to the initial nonspecific interaction, the subsequent phases strictly depend on TBP concentration: at the TBP:ODN ratio of 10:1, the velocity of change of the FRET signal increases approximately 100-fold. PMID- 27667395 TI - Early detection and timely treatment can prevent or delay diabetic retinopathy. PMID- 27667394 TI - Diosgenin-induced autophagy and apoptosis in a human prostate cancer cell line. AB - Diosgenin, a plant steroid compound from Dioscorea nipponica, is an anti inflammatory, antidiabetic, antitumor, vasodilatory compound, which also reduces blood lipid content and protects against ischemia-induced neuronal damage. However, a limited number of studies have been performed on the antitumor effect of diosgenin on prostate cancer, the underlying mechanism of which remains to be fully elucidated. In the present study, the effect and underlying mechanism of diosgenin on DU145 human prostate cancer cells was investigated. DU145 cells were cultured in vitro with diosgenin, following which cell proliferation was detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis was detected by flow cytometry. In addition, DU145 cells were observed under a transmission electron microscope to confirm autophagy. monodansylcadaverine staining and western blotting indicated the levels of autophagy in DU145 cells. To determine the mechanism underlying the effect of diosgenin on DU145 cells, western blotting was performed to evaluate the involvement of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. To investigate the association between apoptosis and autophagy, DU145 cells were cultured with diosgenin and 3-methyladenine. Hoechst 33342/propidium iodide double staining was performed to detect apoptosis, and reverse transcription-quantitative polymerase chain reaction was used to analyze mRNA expression levels of Beclin 1 and B-cell lymphoma 2. Diosgenin inhibits the proliferation of DU145 cells by activating apoptosis and autophagy, and the mechanism underlying this activation may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway. In addition, the inhibition of autophagy mediated by diosgenin increases apoptosis and, thus, increases the therapeutic effect. The combination of diosgenin with an autophagy inhibitor may be an effective strategy to increase the antitumor effect of diosgenin. PMID- 27667396 TI - Textile Organic Electrochemical Transistors as a Platform for Wearable Biosensors. AB - The development of wearable chemical sensors is receiving a great deal of attention in view of non-invasive and continuous monitoring of physiological parameters in healthcare applications. This paper describes the development of a fully textile, wearable chemical sensor based on an organic electrochemical transistor (OECT) entirely made of conductive polymer (PEDOT:PSS). The active polymer patterns are deposited into the fabric by screen printing processes, thus allowing the device to actually "disappear" into it. We demonstrate the reliability of the proposed textile OECTs as a platform for developing chemical sensors capable to detect in real-time various redox active molecules (adrenaline, dopamine and ascorbic acid), by assessing their performance in two different experimental contexts: i) ideal operation conditions (i.e. totally dipped in an electrolyte solution); ii) real-life operation conditions (i.e. by sequentially adding few drops of electrolyte solution onto only one side of the textile sensor). The OECTs response has also been measured in artificial sweat, assessing how these sensors can be reliably used for the detection of biomarkers in body fluids. Finally, the very low operating potentials (<1 V) and absorbed power (~10-4 W) make the here described textile OECTs very appealing for portable and wearable applications. PMID- 27667397 TI - Identification and testing of oviposition attractant chemical compounds for Musca domestica. AB - Oviposition attractants for the house fly Musca domestica have been investigated using electrophysiological tests, behavioural assays and field tests. Volatiles were collected via head space absorption method from fermented wheat bran, fresh wheat bran, rearing substrate residue and house fly maggots. A Y-tube olfactometer assay showed that the odor of fermented wheat bran was a significant attractant for female house flies. Bioactive compounds from fermented wheat bran for house fly females were identified by electrophysiology and mass spectrophotometry and confirmed with standard chemicals. Four electrophysiologically active compounds including ethyl palmitate, ethyl linoleate, methyl linoleate, and linoleic acid were found at a proportion of 10:24:6:0.2. Functional imaging in the female antennal lobes revealed an overlapped active pattern for all chemicals. Further multiple-choice behavioural bioassays showed that these chemicals, as well as a mixture that mimicked the naturally occurring combination, increased the attractiveness of non-preferred rearing substrates of cotton and maize powder. Finally, a field demonstration test revealed that, by adding this mimic blend into a rearing substrate used to attract and breed house flies in West Africa, egg numbers laid by females were increased. These chemicals could be utilized to improve house fly production systems or considered for lure traps. PMID- 27667399 TI - The case of synchronous occurrence of primary adenocarcinoma and squamous cell carcinoma in the same lobe of the lung. AB - Synchronous occurrence of multiple lung cancers in the same lobe of the lung is very rare. Most of the tumors diagnosed in this way have the same histologic type. With imaging methods it is difficult to determine if the multiple lung lesions present hematogenous spread of lung cancer (or cancer from other origin) or these lesions present the second primary lung cancer. We report a rare and unusual case of synchronous occurrence of primary adenocarcinoma and squamous cell carcinoma in the same lobe of the lung. Our case demonstrates that in case of synchronous occurrence of multiple lung lesions each lesion should be sampled and histologic type of every lesion should be determined so the further treatment can be planned accordingly. PMID- 27667398 TI - Discrepancies among Measures of Executive Functioning in a Subsample of Young Adult Survivors of Childhood Brain Tumor: Associations with Treatment Intensity. AB - OBJECTIVES: Treatments for childhood brain tumors (BT) confer substantial risks to neurological development and contribute to neuropsychological deficits in young adulthood. Evidence suggests that individuals who experience more significant neurological insult may lack insight into their neurocognitive limitations. The present study compared survivor, mother, and performance-based estimates of executive functioning (EF), and their associations with treatment intensity history in a subsample of young adult survivors of childhood BTs. METHODS: Thirty-four survivors (52.9% female), aged 18 to 30 years (M=23.5; SD=3.4), 16.1 years post-diagnosis (SD=5.9), were administered self-report and performance-based EF measures. Mothers also rated survivor EF skills. Survivors were classified by treatment intensity history into Minimal, Average/Moderate, or Intensive/Most-Intensive groups. Discrepancies among survivor, mother, and performance-based EF estimates were compared. RESULTS: Survivor-reported and performance-based measures were not correlated, although significant associations were found between mother-reported and performance measures. Survivors in the Intensive/Most-Intensive treatment group evidenced the greatest score discrepancies, reporting less executive dysfunction relative to mother-reported F(2,31)=7.81, p.05). CONCLUSIONS: There may be a lack of agreement among survivor, mother, and performance-based estimates of EF skills in young adult survivors of childhood BT, and these discrepancies may be associated with treatment intensity history. Neuropsychologists should use a multi-method, multi reporter approach to assessment of EF in this population. Providers also should be aware of these discrepancies as they may be a barrier to intervention efforts. (JINS, 2016, 22, 900-910). PMID- 27667400 TI - Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma. AB - Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer. PMID- 27667402 TI - Unions call for action over outstanding appeals. AB - Nursing unions are calling on Health Secretary William Waldegrave to take action over the estimated 20,000 clinical grading appeals still waiting to be heard at district level alone. PMID- 27667401 TI - Rapid Motion Adaptation Reveals the Temporal Dynamics of Spatiotemporal Correlation between ON and OFF Pathways. AB - At the early stages of visual processing, information is processed by two major thalamic pathways encoding brightness increments (ON) and decrements (OFF). Accumulating evidence suggests that these pathways interact and merge as early as in primary visual cortex. Using regular and reverse-phi motion in a rapid adaptation paradigm, we investigated the temporal dynamics of within and across pathway mechanisms for motion processing. When the adaptation duration was short (188 ms), reverse-phi and regular motion led to similar adaptation effects, suggesting that the information from the two pathways are combined efficiently at early-stages of motion processing. However, as the adaption duration was increased to 752 ms, reverse-phi and regular motion showed distinct adaptation effects depending on the test pattern used, either engaging spatiotemporal correlation between the same or opposite contrast polarities. Overall, these findings indicate that spatiotemporal correlation within and across ON-OFF pathways for motion processing can be selectively adapted, and support those models that integrate within and across pathway mechanisms for motion processing. PMID- 27667403 TI - Health unions. AB - Discussions on the timetable for future merger of COHSE, NALGO and NUPE began in London as Nursing Standard went to press. The detailed decisions will be put to union members at their respective conferences later in the year. PMID- 27667404 TI - Opting out leads to job cutbacks. AB - Newly-qualified nurses in Bradford will be out of a job later this month as opting-out hospitals try to cut their costs, it was claimed last week. PMID- 27667405 TI - ? PMID- 27667406 TI - The gulf. AB - Money set aside for Gulf casualties should now be spent on cutting hospital waiting lists, Shadow Health Secretary Robin Cook said last week. PMID- 27667407 TI - Project 2000. AB - The number of student nurses on Project 2000 courses will dwindle unless urgent action is taken to increase bursaries, RCN General Secretary Christine Hancock warned last week. PMID- 27667409 TI - 'Grave concern' over Glasgow understaffing. AB - District nurse staffing levels in Glasgow have now reached unacceptably low levels, RCN Scottish Secretary Irenee O'Neill claimed last week. PMID- 27667408 TI - Minister agrees sale of pioneering nursing home. AB - Health minister Virginia Bottomley has given the go-ahead for a pioneering National Health Service nursing home to be sold off to the independent sector. PMID- 27667410 TI - Changes lead to L80m staff costs. AB - Health authorities are gearing up to spend more than L80 million a year on staff recruited specifically to implement the health service changes, the British Medical Association revealed last week. PMID- 27667412 TI - COHSE sees divisive future for NVQ scheme. AB - Health care training is in danger of becoming an inequitable two-tier system because of the Department of Health's refusal to provide firm direction on the national vocational qualifications scheme, COHSE claims. PMID- 27667411 TI - Ashworth hospital. AB - An inquiry into allegations of patient abuse by nurses at Ashworth Hospital is to be carried out by the Special Hospitals Service Authority after a Channel Four programme last week. The findings will be made public, the Authority's chief executive, Charles Kaye, promised. He said the Authority was 'seriously concerned' by the allegations. PMID- 27667413 TI - 'Fight the repressive traditions' says RCN. AB - Nursing students must fight the profession's repressive 'military-monastic tradition' for the sake of their own futures, RCN General Secretary Christine Hancock urged last week. PMID- 27667414 TI - ? AB - Strange bedfellows: MPs Paul Boateng, labour, Nicholas Scott, Conservative, and Simon Hughes, Liberal Democrat helped launch National Bed Week at the Bed-Making World Record Attempt in Covent Garden last week. PMID- 27667415 TI - GPs and nurses come under fire. AB - GPs offer poor or inadequate advice to couples with fertility problems, and the nursing staff in hospital clinics are often insensitive, a report on NHS infertility services has claimed. PMID- 27667417 TI - Initiative will not be based on clinical need. AB - The Government's former waiting list adviser John Yates has warned that the waiting list initiative will result in non-urgent cases being dealt w'ith at the expense of those with greater clinical need. PMID- 27667418 TI - Nurses welcome decision on prison medical care. AB - Nurses have welcomed reports that NHS staff are to provide health care in prisons with the virtual abolition of the Prison Medical Service. PMID- 27667420 TI - Birth defects not linked to maternal age. AB - Women who delay childbearing until they are over 35 can be reassured by the findings in a major study of birth defects in infants, researchers claim. PMID- 27667421 TI - Leaflet on inherited blood disorders. AB - A new leaflet giving information on thalassaemia and sickle cell anaemia has been produced by haematologists and counsellors working in North East Thames region. PMID- 27667422 TI - Urinary incontinence affects 3.5 million. AB - Research among 4,007 adults aged over 30 has shown more than one in ten have problems with their bladder. PMID- 27667423 TI - Feeding very low birth weight babies. AB - In the absence of breast milk, the incidence of necrotising enterocolitis (NEC) might be reduced by a regimen developed in the Netherlands. PMID- 27667424 TI - High cardiac risk in snow clearing. AB - The recent bad weather has produced an unusual presentation of myocardial infarction snow shoveller's infarction. PMID- 27667425 TI - Rectal examination for abdominal pain. AB - Rectal examination does not provide any additional diagnostic information than testing for rebound tenderness in patients with right lower quadrant abdominal pain. PMID- 27667426 TI - Effective service for outpatient clinics. AB - Routine follow-up appointments following hospital admission or initial clinic referral should be avoided and, if initiated, a precise reason for the appointment should be identified. PMID- 27667427 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Clare Ward, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA 1 2AX (Fax 081-423 3867). PMID- 27667428 TI - Entering a very different world. AB - While Linda Humphreys was a patient in a psychiatric hospital she set fire to bedding and a tea towel and was subsequently charged with two counts of arson. At her recent trial, North Wales Hospital in Denbigh was said to be unable to take her back. Referral to Ashworth, the special hospital, was ruled out as the admission process was 'causing some delay'. She has no fixed address and the court was awaiting psychiatric reports. Magistrates said they had no option but to return her, for the sixth time, to Risley Remand Centre. PMID- 27667429 TI - In need of peer support. AB - I was interested to read Caroline Hiscox's study on stress and its management and the formation of support groups (Nursing Standard February 13). PMID- 27667430 TI - Health visitors' responsibility. AB - I read with disappointment the reaction of health visitors to Home Office Minister John Patten's remarks as reported in Nursing Standard (News, February 20). PMID- 27667432 TI - Permission granted. AB - I would like to respond to Diane Marks-Maran's quote in the Everyday Ethics Conference report, 'Daily ethical conflicts', which was reported in Nursing Standard (News, February 27). PMID- 27667433 TI - Nightingale bursaries. AB - This year the Florence Nightingale Museum Trustees plan to award a number of bursaries to those registered and enrolled nurses who plan to undertake district nurse training. PMID- 27667431 TI - Following up discharge. AB - I read with interest the article by Helen Evers on issues in community care services (Nursing Standard February 13), but feel she failed to address one very important aspect of discharge - the numbers of elderly people being discharged from hospital who do not require specific district nurse care bur who do, nevertheless, require follow-up by a worker with a nursing background. PMID- 27667434 TI - Understanding disability. AB - I am writing to congratulate you on Jan Dewing's long-overdue article about physically disabled people in acute settings (Nursing Standard February 20). PMID- 27667435 TI - A conference not to miss. AB - The Leukaemia and Bone Marrow Transplant Forum of the Royal College of Nursing is holding a conference on April 24 1991 which will address the impact of new professional issues on a particularly specialised area of care, and one which is easily overlooked. PMID- 27667436 TI - Information exchange. AB - We run an eight-bedded unit in neuropsychiatry specifically for the assessment, rehabilitation and respite care of people under 65 years old who have acquired cognitive impairment with associated psychiatric and behavioural problems. PMID- 27667437 TI - Gossip. AB - There is at least something to celebrate in the fact that the Gulf War has been concluded with a very small number of casualties having to be brought to Britain though of course, even one casualty is one too many. PMID- 27667438 TI - Spotlight on Scotland. PMID- 27667439 TI - Research and statistics Research and statistics C M Hicks Prentice-Hall 326pp L12.95 0-13-844077-8 [Formula: see text]. AB - At last, amid the recent shower of research and statistics textbooks, we finally have one by a British author. Carolyn Hicks, a ' senior lecturer in psychology at the University of Birmingham, has come up ' with a text that will be useful to the growing band of nurses involved in the research process. PMID- 27667440 TI - The fertility and contraception book The fertility and contraception book J Mosse and J Heaton Faber 400pp L7.99 0-571-15173-6 [Formula: see text]. AB - The Fertility and Contraception Book is a comprehensive guide to both; it's interesting and easy to read. Julia Mosse and Josephine Heaton explain at the outset that they are attempting to deal only with these topics. PMID- 27667441 TI - Oncology nursing Oncology nursing P Ashwanden et al Aspen 39-lpp L37.95 0-8342 0168-2 [Formula: see text]. AB - My feelings about Oncology Nursing are ambivalent. I genuinely enjoyed reading what our US counterparts are up to, but wonder just how relevant an American text is to British nursing. PMID- 27667442 TI - Histone Deacetylase Inhibitor Phenylbutyrate Exaggerates Heart Failure in Pressure Overloaded Mice independently of HDAC inhibition. AB - 4-Sodium phenylbutyrate (PBA) has been reported to inhibit endoplasmic reticulum stress and histone deacetylation (HDAC), both of which are novel therapeutic targets for cardiac hypertrophy and heart failure. However, it is unclear whether PBA can improve heart function. Here, we tested the effects of PBA and some other HDAC inhibitors on cardiac dysfunction induced by pressure overload. Transverse aortic constriction (TAC) was performed on male C57BL/6 mice. PBA treatment (100 mg/kg, 6 weeks) unexpectedly led to a higher mortality, exacerbated cardiac remodelling and dysfunction. Similar results were noted in TAC mice treated with butyrate sodium (BS), a PBA analogue. In contrast, other HDAC inhibitors, valproic acid (VAL) and trichostatin A (TSA), improved the survival. All four HDAC inhibitors induced histone H3 acetylation and inhibited HDAC total activity. An individual HDAC activity assay showed that rather than class IIa members (HDAC4 and 7), PBA and BS predominantly inhibited class I members (HDAC2 and 8), whereas VAL and TSA inhibited all of them. These findings indicate that PBA and BS accelerate cardiac hypertrophy and dysfunction, whereas VAL and TSA have opposing effects. PMID- 27667444 TI - Enhancement of trichothecene mycotoxins of Fusarium oxysporum by ferulic acid aggravates oxidative damage in Rehmannia glutinosa Libosch. AB - Rehmannia glutinosa is an important medicinal herb that cannot be replanted in the same field due to the effects of autotoxic substances. The effects of these substances on R. glutinosa in continuous cropping systems are unknown. In the present study, bioassays revealed that R. glutinosa exhibited severe growth restriction and higher disease indices in the FO+FA (F.oxysporum pretreated with ferulic acid) treatment. The increases in the contents of MDA and H2O2 were greater in the FA+FO treatment than in the FA or FO only treatments, respectively. Consistent with this result, the enzyme activities in the seedlings increased with treatment time. To identify the main factor underlying the increased pathogenicity of FO, macroconidia and trichothecene mycotoxins coproduced by FO were separated and used to treat R. glutinosa seedlings. The MDA and H2O2 contents were similar in the seedlings treated with deoxynivalenol and in the FA+FO treatment. Quantification of the relative expression of certain genes involved in Ca2+ signal transduction pathways suggested that trichothecene mycotoxins play an important role in the increased pathogenicity of FO. In conclusion, FA not only directly enhances oxidative damage in R. glutinosa but also increases wilting symptom outbreaks by promoting the secretion of trichothecene mycotoxins by FO. PMID- 27667443 TI - Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists. AB - Knockout mice studies implicate the mammalian short-chain fatty acid (SCFA) receptors, FFAR2 and FFAR3- in colitis, arthritis and asthma. However, the correlation with human biology is uncertain. Here, we detected FFAR2 and FFAR3 expression in human monocytes via immunohistochemistry. Upon treatment with acetate SCFA or FFAR2- and FFAR3-specific synthetic agonists, human monocytes displayed elevated p38 phosphorylation and attenuated C5, CCL1, CCL2, GM-CSF, IL 1alpha, IL-1beta and ICAM-1 inflammatory cytokine expression. Acetate and FFAR2 agonist treatment also repressed Akt and ERK2 signalling. Surprisingly, mouse monocytes displayed a distinct response to acetate treatment, elevating GM-CSF, IL-1alpha, and IL-1beta cytokine expression. This effect persisted in FFAR2/3 knockout mouse monocytes and was not reproduced by synthetic agonists, suggesting a FFAR2/3 independent mechanism in mice. Collectively, we show that SCFAs act via FFAR2/3 to modulate human monocyte inflammatory responses- a pathway that is absent in mouse monocytes. PMID- 27667445 TI - 3D-QSAR analysis of a series of S-DABO derivatives as anti-HIV agents by CoMFA and CoMSIA. AB - In this study, we retrieved a series of 59 dihydroalkylthio-benzyloxopyrimidine (S-DABO) derivatives, which is a class of highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) reported from published articles, and analysed them with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Statistically significant three dimensional quantitative structure-activity relationship (3D-QSAR) models by CoMFA and CoMSIA were derived from a training set of 46 compounds on the basis of the rigid body alignment. Further, the predictive ability of the QSAR models was validated by a test set of 13 compounds. Based on the information derived from CoMFA and CoMSIA contour maps, we have identified some steric and electrostatic features for improving the activities of these inhibitors, and we validated the 3D-QSAR results by a molecular docking method. On the basis of the obtained results, we designed a new series of S-DABO derivatives with high activities. Therefore, this study could be utilized to design more potent S-DABO analogues as anti-HIV agents. PMID- 27667446 TI - Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis. AB - Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 +/- 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 +/- 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population. PMID- 27667447 TI - The clinical experience of robot-assisted surgery in gynecologic cancer. AB - The comparison of robotic and conventional laparoscopic hysterectomy and pelvic lymphadenectomy in gynecologic cancer still needs to be studied. In all, 98 consecutive cases of patients with gynecologic cancer undergoing robot-assisted hysterectomy and pelvic lymphadenectomy, and another 98 consecutive cases of conventional laparoscopic hysterectomy and pelvic lymphadenectomy during the same period in the Obstetrics and Gynecology Hospital of Fudan University were included. The duration of the operation, blood loss, drainage during the first 24 h after the operation, total hospital stay, hospital stay after the operation, lymph nodes collected, perioperative complications, and the cost of each operation for both procedures were recorded. The duration of the operation was longer, and the cost of each operation was almost seven times higher in the robot group than that in the conventional laparoscopy group. But the differences with regard to blood loss, drainage during the first 24 h after the operation, total hospital stay, hospital stay after operation, the lymph nodes collected, and the rate of perioperative complications were not statistically significant. Robot assisted surgery (RAS) in gynecologic cancer is as feasible as conventional laparoscopic surgery. We recommend further studies about the cost and effect of RAS in gynecologic cancer. PMID- 27667449 TI - Near-Infrared Light-Mediated Photodynamic Therapy Nanoplatform by the Electrostatic Assembly of Upconversion Nanoparticles with Graphitic Carbon Nitride Quantum Dots. AB - Photodynamic therapy (PDT) is a promising antitumor treatment that is based on photosensitizers. This therapy kills cancer cells by generating reactive oxygen species (ROS) after irradiation with specific laser wavelengths. Being a potential photosensitizer, graphitic carbon nitride (g-C3N4) quantum dots (QDs) are noncytotoxic. Although the use of g-C3N4 QDs is challenged by the limited tissue penetration of UV light, g-C3N4 QDs display excellent ultraviolet (UV) light-triggered cytotoxicity. The g-C3N4 QDs were synthesized using a solid-phase hydrothermal method. The well-distributed hydrophilic g-C3N4 can be combined with NaYF4:Yb3+/Tm3+ upconversion nanoparticles via the positive ligand poly(l-lysine) to produce the final nanocomposite, NaYF4:Yb/Tm-PLL@g-C3N4. Upconversion nanoparticles can transfer IR light into UV light and promote g-C3N4 to release blue-to-green visible light to generate different images. Moreover, g-C3N4 is a promising photosensitizer in PDT because g-C3N4 can transfer oxygen into toxic ROS. The singlet oxygen formed by g-C3N4 displays great potential for use in the treatment of cancer. PMID- 27667450 TI - [Protective effect and mechanism of neutrophil gelatinase-associated lipocalin against hypoxia/reoxygenation injury of HK-2 renal tubular epithelial cells]. AB - Objective To study the role of neutrophil gelatinase-associated lipocalin (NGAL) in hypoxia/reoxygenation injury and its regulatory effect on autophagy in HK-2 renal tubular epithelial cells. Methods Three sets of designed NGAL short-hairpin RNA (shRNA) sequences were synthesized and transfected into HK-2 cells. The expression levels of NGAL mRNA and protein were analyzed by quantitative real time PCR and Western blotting, respectively. Then, the HK-2 cells with the best NGAL mRNA interference were selected to establish the hypoxia/reoxygenation model. The levels of microtubule-associated protein 1 light chain 3II (LC-3II) and beclin-1 were detected by Western blotting. Besides, the viability of cells was tested by Cell Titer-Blue and CCK-8 assay. Results Three sets of shRNA plasmids carrying silenced NGAL gene were successfully constructed and transfected into HK-2 cells. The expressions of NGAL mRNA and protein in these cells were significantly lower than those in the controls with blank vector. After NGAL-silenced HK-2 cells were subjected to hypoxia/reoxygenation, the levels of LC-3 II and beclin-1 were lower than those in the controls with blank vector, whereas the levels of LC-3 II and beclin-1 in were higher than those in the ones in which 400 ng/mL recombinant NGAL was added. Cell Titer-Blue and CCK-8 assays showed that the viability of NGAL-knockdown HK-2 cells was significantly lower than the controls. Conclusion NGAL may plays protective role towards HK-2 cells in the process of hypoxia/reoxygenation by enhancing autophagy. PMID- 27667451 TI - [Brd3 promotes IL-6 production via enhancing acetylase CBP recruitment and histone 3 acetylation within IL6 promoter]. AB - Objective To investigate the role of bromodomain containing 3 (Brd3) in LPS triggered interleukin-6 (IL-6) production in macrophages and the underlying mechanism. Methods CRISPR-Cas9 technology was used to screen an RAW264.7 cell line with Brd3 knockout (Brd3-/-). The Brd3-/- cells were used as an experimental group, and the parential cells expressing wide-type Brd3 as a control group. The IL-6 level in cell culture supernatant was detected by ELISA after 100 ng/mL LPS challenging. Effect of Brd3 knockout on the expression and activation of signal pathways involved in IL-6 expression, including the NF-kappaB and mitogen activated protein kinase (MAPK) pathways were examined by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to evaluate the recruitment of acetylase CREB-binding protein (CBP) to IL6 gene promoter and the acetylation level of histone 3 within IL6 gene promoter. Results LPS treatment significantly downregulated Brd3 expression in mouse peritoneal macrophages. LPS-induced production of IL-6 was significantly inhibited in Brd3-/- macrophages. The expressions and activation of signal molecules within NF-kappaB and MAPK pathways were barely affected. Brd3 knockout significantly decreased the recruitment of acetylase CBP to IL6 gene promoter, and the acetylation level of histone3 within IL6 gene promoter was also repressed. Conclusion Brd3 promotes LPS-triggered IL-6 production via promoting the recruitment of CBP to IL6 promoter and enhancing the acetylation level of histone 3 within IL6 promoter. PMID- 27667448 TI - Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd. AB - Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization. PMID- 27667452 TI - [Comparison of the characteristics of expanded cells in human PBMCs activated by combination of MTB-Ag and IL-15 or IL-2 in vitro]. AB - Objective To investigate the biological characteristics of expanded cells in human peripheral blood mononuclear cells (PBMCs) activated by the combination of Mycobacterium tuberculosis antigen (MTB-Ag) and IL-15 or IL-2 in vitro. Methods Fresh PBMCs of normal subjects were stimulated with MTB-Ag and IL-15 or MTB-Ag and IL-2 for 12 days. Proportions of gamma delta T cells, natural killer (NK) cells and CD4+ T cells in the expanded cells were analyzed by flow cytometry; the numbers of the three lymphocytes were counted by an automated cell counter; the killing activity of the expanded cells against tumor cells was tested by MTT assay. Results Compared with MTB-Ag plus IL-2 group, proportion of gammadelta T cells was higher significantly, and proportion of NK cells was lower significantly in MTB-Ag plus IL-15 group. There was no statistically significant difference in CD4+ T cell proportion between the two groups. And the same results could be obtained in counting the numbers of the three lymphocytes in both groups. And killing activity of expanded cells from both groups against tumor cells was very strong, and there was no statistically significant difference between both groups. Conclusion gamma delta T cells can be activated and expanded in human PBMCs stimulated by MTB-Ag and IL-15 greatly, and the total expanded cells have high cytotoxicity against tumor cells in vitro. PMID- 27667453 TI - [Mitochondrial signal peptide guides EGFP-GRP75 fusion proteins into mitochondria]. AB - Objective To investigate the role of mitoch-ondrial signal peptide in guiding enhanced green fluorescent protein-glucose-regulated protein 75 fusion proteins (EGFP-GRP75) into mitochondria. Methods At first, the signal peptide gene and GRP75 domain genes were spliced by overlap extension PCR. Unphosphorylatable mutant T62A/S65A, phospho-mimic mutant T62D/S65D and substrate binding-defective mutant V482F were further created through site-directed mutagenesis PCR. The fusion gene fragments were ligated into pEGFPC1 expression plasmid, respectively. The expressions of EGFP-GRP75 fusion constructs in HeLa cells were examined directly with Western blotting and laser scanning confocal microscopy. Results All the fusion proteins were highly expressed. Signal peptide remarkably reduced the expression of EGFP-GRP75 fusions compared with recombinant plasmids without signal peptide. Fluorescence was seen exclusively located in mitochondria of the cells transfected by signal peptide-contained plasmids, whereas signal peptide absent EGFP-GRP75 fusion proteins were homogeneously distributed in the whole cell body. In addition, no changes were observed in the subcellular localization of EGFP-GRP75 fusion proteins that contained double or triple mutations at Thr 62 residues, Ser 65 residues and Val 482 residues. Conclusion Signal peptide is essential for targeting EGFP-GRP75 fusion proteins into mitochondria, and 62 threonine/65 serine/482 valine residues contribute to phosphorylation or substrate-binding characteristics are dispensable in the mitochondrial targeting function. PMID- 27667454 TI - [Zinc-dependent metalloprotease 1 (Zmp1) inhibits the proliferation and phagosome lysosome fusion of mouse macrophage RAW264.7]. AB - Objective To observe the effect of zinc-dependent metalloprotease 1 (Zmp1) of Bacillus Calmette Guerin vaccine (BCG) on the proliferation and phagosome lysosome fusion of RAW264.7 mouse macrophage. Methods Zmp1 was expressed in E.coli BL21 (DE3) and purified by metal chelate magnetic beads. RAW264.7 cells were incubated with the purified Zmp1. Cell proliferation was detected at 0, 24, 48, 72 and 96 hours by cell counting kit-8 (CCK-8) assay and cell cycle distribution was detected by flow cytometry (FCM). The formation of phagosome was induced after RAW264.7 cells were infected with attenuated Salmonella. Attenuated Salmonella in phagosomes and lysosome associated membrane protein 1 (LAMP1) were marked by Alexa FluorR350-anti-Salmonella antibodies (blue fluorescence) and Cy5 anti-LAMP1 antibodies (red fluorescence), respectively. Two kind of fluorescence in RAW264.7 cells were observed under a fluorescent microscope and the fusion of phagosome and lysosome was analyzed by overlaying two kind of fluorescence (purple fluorescence). Results RAW264.7 cell proliferation decreased obviously 48 hours after treated with Zmp1, and the cell count in G1 phase declined, but the number of S-phase cells increased. In RAW264.7 cells infected with attenuated Salmonella and labeled by double immunofluorescent staining, phagolysosomes exhibiting purple fluorescence were reduced after treated by Zmp1. Conclusion Zmp1 can inhibit mouse RAW264.7 cell proliferation and phagosome-lysosome fusion. PMID- 27667455 TI - [Protein kinase A inhibitor H-89 blocks polyploidization of SP600125-induced CMK cells by regulating phosphorylation of ribosomal protein S6 kinase 1]. AB - Objective To investigate the regulatory effect of post-translation modification of ribosomal protein S6 kinase 1 (S6K1) on the polyploidization of megakaryocytes. Methods SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, and H-89, a cAMP-dependent protein kinase (PKA) inhibitor, were used to treat CMK cells separately or in combination. With propidium iodide (PI) to dye DNA in the treated cells, the relative DNA content was detected by flow cytometry, and then the DNA polyploidy was analyzed. The change of expression and phosphorylation of ribosomal protein S6 kinase 1 (S6K1), an important mammalian target of rapamycin (mTOR) downstream target molecule, was analyzed by Western blotting. Molecular docking study and kinase activity assay were performed to analyze the combination of H-89 with S6K1 and the effect of H-89 on the activity of S6K1 kinase. Results SP600125 induced CMK cell polyploidization in a time-dependent and dose-dependent manner. At the same time, it increased the phosphorylation of S6K1 at Thr421/Ser424 and decreased the phosphorylation of S6K1 at Thr389. H-89 not only blocked polyploidization, but also decreased the phosphorylation of S6K1 at Thr421/Ser424 and increased the phosphorylation of S6K1 at Thr389. Molecular docking and kinase activity assay showed that H-89 occupied the ATP binding sites of S6K1 and inhibited its activity. Noticeably, both H-89 and SP600125 inhibited the activity of PKA. Moreover, the two drugs further inhibited the activity of PKA when used together. Therefore, these data indicated that H-89 blocked the SP600125-induced polyploidization of CMK cells mainly by changing S6K1 phosphorylation state, rather than its inhibitory effect on PKA. Conclusion H-89 can block the polyploidization of SP600125-induced CMK cells by regulating S6K1 phosphorylation state. PMID- 27667456 TI - [Expression and localization of zinc finger protein 185 in sperm cells, Leydig cells and Sertoli cells of mouse testis]. AB - Objective To investigate the expression of zinc finger protein 185 (ZNF185) in the sperm cells, Leydig cells and Sertoli cells of the mouse testis. Methods The localization of ZNF185 in the sperm cells, Leydig cells, Sertoli cells and mouse testis tissue was detected by immunofluorescence assay. The mRNA and protein expression levels of ZNF185 in the three kinds of cells were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Results Immunofluorescence assay showed that ZNF185 was expressed in sperm cells, Leydig cells and Sertoli cells, furthermore, ZNF185 was mainly distributed in the cytoplasm of Leydig cells and Sertoli cells, as well as the head and tail of sperm cells. The qRT-PCR and Western blotting showed that the mRNA and protein expression levels of ZNF185 in Sertoli cells were significantly lower than those in Leydig cells and sperm cells. Conclusion ZNF185 is distributed in sperm cells, Leydig cells and Sertoli cells of mouse testis, and the expression level was different between them. PMID- 27667457 TI - [Canine zona pellucida 3 (CZP3) DNA vaccination reduces mouse fertility effectively]. AB - Objective To construct a DNA contraception vaccine targeting canine zona pellucida 3 (CZP3) antigen and assess the immunological efficacy and contraceptive effect of the vaccine. Methods The CZP3 gene was amplified from total RNA of canine ovary by reverse transcription PCR and analyzed by bioinformatics, such as ProtScale, TMHMM, Signal P, InterProScan, PREDICT PROTEIN, homology modeling, etc. The constructed DNA vaccine pcDNA-CZP3 was used to vaccinate mice, and then its immune effect and contraceptive effect were evaluated in the mice. Results The CZP3 gene had 426 amino acids with two hydrophobic regions at its N-terminal and C-terminal, respectively. The top 22 amino acids at the N-terminal of the CZP3 was the signal peptide and there was a transmembranous helix from extracellular to intracellular at the C-terminal. CZP3 also had 8 B cell epitopes. The DNA contraception vaccine pcDNA3-CZP3 induced high levels of antibody and lower average litter size of mouse compared with the blank and negative control groups significantly. Conclusion The canine contraception DNA vaccine pcDNA-CZP3 has been successfully constructed and it can reduce the mouse fertility remarkably. PMID- 27667458 TI - [SP600125-induced polyploidization of megakaryocytic leukemia cell lines by ribosomal protein S6 kinase 1 depends on the degree of cell differentiation]. AB - Objective To investigate regulatory role of ribosomal protein S6 kinase 1 (S6K1) in the polyploidization of different megakaryocytic leukemia cell lines at the different differentiation stages. Methods Megakaryocytic leukemia cell lines (Dami, Meg-01 and HEL cells) were induced towards polyploidization by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. The SP600125-inducing process was blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor. The phenotype (CD41a, CD42a and CD42b) and DNA ploidy were detected by flow cytometry. The expression and phosphorylation of S6K1 and related proteins were detected by Western blotting. Results SP600125 induced polyploidization and increased the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) in Dami, Meg-01 and HEL cells. However, the effect of SP600125 on polyploidization of the three cell lines was different, with the strongest effect on Dami cells and the weakest on Meg-01 cells. Moreover, SP600125 increased the phosphorylation of S6K1 Thr421/Ser424 and decreased the phosphorylation of Thr389 in Dami cells. However, it only increased the phosphorylation of Thr389 in HEL cells and had no effect on the phosphorylation of S6K1 in Meg-01 cells. Interestingly, H-89 only partially blocked the polyploidization of Dami cells, although it decreased the phosphorylation of 4E-BP1 in all SP600125-induced three cell lines. Noticeably, H 89 decreased the phosphorylation of S6K1 Thr421/Ser424 and increased the phosphorylation of Thr389 in Dami cells. However, H-89 had no effect on the phosphorylation of Thr421/Ser424, although it increased the phosphorylation of Thr389 in Meg-01 and HEL cells. Phenotypic analysis showed that the three cell lines were at different levels of differentiation in megakaryocytic lineage, with the highest differentiation in Dami and the lowest in Meg-01 cells. Conclusion SP600125-induced polyploidization of megakaryocytic leukemia cell lines is dependent on the effect of SP600125 on phosphorylation of S6K1 in cell lines at the different differentiation stages. PMID- 27667459 TI - [Emodin alleviates pulmonary fibrosis through inactivation of TGF-beta1/ADAMTS-1 signaling pathway in rats]. AB - Objective To explore the role of transforming growth factor-beta1 (TGF-beta1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS 1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group. From the second day, rats in the low- and high-dose emodin intervention groups were intragastrically treated with 2 mL of 20 and 80 mg/kg emodin, respectively. Rats in the prednisone group were intragastrically administrated with 2 mL of 5 mg/kg prednisone acetate. However, rats in the normal control and sham-operated and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28 after modeling. Subsequently, blood and pulmonary tissue specimen were taken. The pathological changes of pulmonary tissues were observed using routine HE and Masson staining. The expressions of TGF-beta1, ADAMTS-1, collagen type 1 (Col1) and Col3 in pulmonary tissues were measured by quantitative real-time PCR and Western blotting. Serum levels of procollagen type 1 carboxy terminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) were detected by ELISA. Results Compare with the model group, the alveolitis and pulmonary fibrosis extent in each drug-treated group were significantly alleviated. In comparison with normal control group or sham-operated group, the mRNA and protein levels of TGF-beta1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP increased, but the mRNA and protein levels of ADAMTS-1 decreased in model group. After treatment with low- and high-dose emodin or prednisone, the mRNA and protein levels of TGF-beta1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP were significantly downregulated, while the mRNA and protein levels of ADAMTS-1 in pulmonary tissues were significantly upregulated as compared with the model group. Moreover, In comparison with the low-dose emodin intervention group, the above indicators were significantly improved in the high dose emodin intervention or prednisone group. However, the above indicators were not significantly different between the high-dose emodin intervention group and the prednisone group. Conclusion Increased degradation of Col1 and Col3 in pulmonary tissues due to the inactivation of TGF-beta1/ADAMTS-1 signaling pathway may be a significant mechanism by which emodin protects rats against pulmonary fibrosis. PMID- 27667460 TI - [Human placental mesenchymal stem cells of fetal origin relieves mouse pulmonary fibrosis via downregulating MyD88 and TGF-beta signaling pathway]. AB - Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 MUg/L, 50 MUL) via intratracheal instillation. The mice in negative control group were instilled with PBS (50 MUL) through the same manner of the other two groups. Three days post-modelling, 200 MUL containing 5*105 hfPMSCs were injected into hfPMSCs transplantation group via tail vein. All the mice were sacrificed at day 21 after modeling in batch. Lung tissues were collected for analyzing the pathological changes by HE staining and Masson staining as well as detecting collagen content. The total protein of lung tissues was extracted for observing the expressions of myeloid differentiation factor 88 (MyD88) and transforming growth factor-beta (TGF-beta); the level of TGF-beta in sera was determined by Western blotting. Results The hfPMSCs possessed the morphology of mesenchymal stem cells and expressed the surface markers CD73, CD90 and CD105, but did not express CD14, CD34 and CD45. HE and Masson staining showed that hfPMSCs transplantation significantly reduced the degree of pulmonary fibrosis compared with bleomycin treatment group. The collagen content and the expression levels of MyD88 and TGF-beta in bleomycin treatment group were obviously higher than those in hfPMSCs transplantation group and negative control group. Conclusion hfPMSCs possess the capability of alleviating pulmonary fibrosis by down-regulating the expressions of MyD88 and TGF-beta. PMID- 27667461 TI - [Berberine inhibits cardiac fibrosis of diabetic rats]. AB - Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-beta1 (TGF beta1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-beta1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-beta1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down regulating the expressions of TGF-beta1 and CTGF and reducing the synthesis and deposition of Col1 and Col3. PMID- 27667462 TI - [Preparation and activity validation of PP7 bacteriophage-like particles displaying PAP114-128 peptide]. AB - Objective To obtain the PP7 bacteriophage-like particles carrying the peptide of prostatic acid phosphatase PAP114-128, and prove that they retain the original biological activity. Methods First, the plasmid pETDuet-2PP7 was constructed as follows: the gene of PP7 coat protein dimer was amplified by gene mutation combined with overlapping PCR technology, and inserted into the vector pETDuet-1. Following that, the plasmid pETDuet-2PP7-PAP114-128 was constructed as follows: the PP7 coat protein gene carrying the coding gene of PAP114-128 peptide was amplified using PCR, and then inserted into the vector pETDuet-2PP7. Both pETDuet 2PP7 and pETDuet-2PP7-PAP114-128 were transformed into E.coli and expressed. The expression product was verified by SDS-PAGE, double immunodiffusion assay and ELISA. Results The gene fragment of PP7 coat protein dimer was obtained by overlapping PCR using Ex Taq DNA polymerase, and the antigenicity of its expression product was the same as that of the coat protein of wild-type PP7 bacteriophage. Moreover, the PAP114-128 peptide epitope that was displayed on the surface of PP7 bacteriophage was identical with the corresponding epitope of natural human PAP, and it was able to induce high levels of antibodies. Conclusion The gene of PP7 coat protein dimer with repeated sequences can be prepared by gene mutation combined with overlapping PCR. Based on this, PP7 bacteriophage-like particles carrying PAP peptide can be prepared, which not only solves the problem of the instability of the peptides, but also lays a foundation for the study on their delivery and function. PMID- 27667463 TI - [Recombinant HMGB1 induces the differentiation of mouse myeloid cells into myeloid-derived suppressor cells in vitro]. AB - Objective To investigate the effects of recombinant high mobility group box l (rHMGB1) on the differentiation of myeloid-derived suppressor cells (MDSCs) in vitro. Methods The cells were harvested from the bone marrow of BALB/c mice and cultured with rHMGB1, granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with IL-6 (GM-CSF-IL-6), GM-CSF combined with IL-6 and rHMGB1 (GM-CSF-IL 6-rHMGB1), separately in vitro. The percentages of CD11b+Gr1+MDSCs, CD11c+ cells and F4/80+ macrophages were measured by flow cycometry (FCM) after treatment for 48 hours. Monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs) were isolated from the femurs of healthy BALB/c mice, and then stimulated with rHMGB1. The proportions of CD11b+Gr1+MDSCs, CD11c+ cells and F4/80+ macrophages were detected by FCM. Results FCM showed that the proportions of CD11b+Gr1+MDSCs in rHMGB1 group, GM-CSF-IL-6 group, GM-CSF-IL-6-HMGB1 group increased, while CD11c+ cells and F4/80+ macrophages decreased as compared with control group after 48 hours. Following rHMGB1 treatment, the percentages of M-MDSCs and G-MDSCs were raised and the proportions of CD11c+ cells and F4/80+ macrophages were reduced in rHMGB1-treated group, but there were no significant differences between M-MDSCs and G-MDSCs groups. Conclusion The rHMGB1 can induce MDSC differentiation; rHMGB1 combined with GM-CSF and IL-6 can more effectively promote MDSC differentiation in vitro. PMID- 27667464 TI - [Xinfeng Capsule reduces hypercoagulative state in patients with Sjogren's syndrome by inhibiting miR-155/SOCS1/NF-kappaB signaling pathway]. AB - Objective To explore the relationship between Xinfeng Capsule (XFC) improving the hypercoagulative state in patients with Sjogren's syndrome (SS) and miR 155/suppressor of cytokine signaling 1 (SOCS1)/nuclear factor kappaB (NF-kappaB) signaling pathway. Methods Sixty-six SS patients were randomly divided into XFC treated group and hydroxychloroquine (HCQ)-treated control group (n=33 per group), which were respectively treated with XFC and HCQ. In addition, 20 healthy volunteers were enrolled as a normal control group. The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIG), thrombin time (TT) and D-dimer (D-D) were detected using automatic coagulation analyzer. Interleukin-1beta (IL-1beta), IL-4, IL-10, tumor necrosis factor-alpha (TNF-alpha), P50, P65, inhibitor of NF-kappaB alpha (IkappaBalpha) were tested using ELISA. Meanwhile, the mRNA expressions of p50, p65 and IkappaBalpha were determined using quantitative real-time PCR, and the level of microRNA-155 (miR 155) was examined by one-step fluorescence quantitative PCR. The protein levels of P50, P65 and SOCS1 were detected using Western blotting. Erythrocyte sedimentation rate (ESR) was evaluated by Westergren method. Hypersensitive C reactive protein (hs-CRP) was detected using automatic biochemical analyzer. Results Compared with the normal control group, the levels of D-D and FIB significantly increased in SS group; simultaneously, the serum levels of miR-155, IL-1beta, TNF-alpha, P50, P65, IkappaBalpha, hs-CRP, ESR were significantly elevated in SS patients, while IL-4 and IL-10 were significantly reduced. Spearman correlation analysis showed that the coagulation parameters were remarkably correlated with cytokines, NF-kappaB and activity indexes. In the two treated groups, coagulation parameters and related indexes were demonstrated having some improvement, especially in the XFC group, which had a much higher efficiency, and better outcomes in reducing the levels of FIB, D-D, miR-155, TNF alpha, IL-1beta, P50, P65, ESR and hs-CRP, as well as increasing the expressions of SOCS1, IL-4 and IL-10. Conclusion XFC can significantly alleviate the hypercoagulative state of patients with SS, and the mechanisms may be related to the inhibition of miR-155/SOCS1/NF-kappaB signaling pathway. PMID- 27667465 TI - [Upregulated PD-1 on CD8+T cells is positively correlated with activation of T cells during HIV-1 infection]. AB - Objective To investigate the expressions of programmed death-1 (PD-1), CD38, human leukocyte antigen DR (HLA-DR) and anligen KI-67(ki67) on CD8+ T cells, and the correlation between PD-1/PD-L1 pathway and activation, immunodepletion during HIV-1 infection. Methods Peripheral blood mononuclear cells were isolated by density gradient centrifugation from 87 HIV-1 patients and 22 healthy controls. The expression levels of PD-1, CD38, HLA-DR and ki67 on CD8+T cells were detected by flow cytometry. Furthermore, we evaluated the production of interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in CD8+ T cells by blocking PD-1/PD-L1 pathway in the presence of PD-L1 mAb. Results Compared with healthy controls, HIV-1 infection resulted in a significant increase in PD-1 expression on CD8+T cells. Correlation analysis showed that PD-1 expression on CD8+T cell was positively associated with HIV-1 viral loading (VL) and negatively associated with the number of CD4+T cells. Furthermore, PD-1 expression was positively correlated with CD38 and HLA-DR expressions on CD8+T cells in HIV-1 infected patients. There was no association between PD-1 and ki67 expression on CD8+T cells in HIV-1 infected patients. Blockage of the PD-1/PD-L1 pathway increased TNF-alpha and IFN-gamma production in CD8+T cells. Conclusion PD-1 expression on CD8+T cells is significantly upregulated during HIV-1 infection. PD 1 expression is correlated with CD8+T cell inhibition, immunodepletion and disease progression. Moreover, the blockage of PD-1/PD-L1 pathway can restore the function of CD8+T cells in HIV-1 patients. PMID- 27667466 TI - [The poor chemotherapeutic efficacy in lung adenocarcinoma overexpressing c-Src and nucleophosmin/B23(NPM1)]. AB - Objective To observe the expressions of c-Src protein and nucleophosmin/B23 (NPM1) protein in lung adenocarcinoma tissues and explore their relationships with chemotherapeutic efficacy. Methods The study collected a total of 107 lung adenocarcinoma tissue specimens from the First People's Hospital of Huaihua City from 2012-10-10 to 2015-06-30. Immunohistochemistry was used to analyze the expressions of c-Src protein and NPM1 protein. The relationships between the protein expressions and lung adenocarcinoma progression were subsequently analyzed. Among these patients, 55 cases of III-IV patients were treated with gemcitabine combined with cisplatin for 4 cycles of chemotherapy. The relationships between the protein expressions and chemotherapeutic efficacy were then analyzed. Results Both c-Src protein and NPM1 protein were positively expressed in lung adenocarcinoma tissues. With the increase of clinical stages, their expression levels gradually increased. However, their levels showed an inverse correlation with tumor differentiation degree. Chemotherapeutic efficacy decreased with the increase of the protein expressions. Conclusion Chemotherapeutic sensitivity is poor in lung adenocarcinoma patients overexpressing c-Src and NPM1 protein. High expressions of c-Src and NPM1 may be associated with poorly differentiated adenocarcinoma. PMID- 27667467 TI - [The number of myeloid suppressor cells, Th17 cells of peripheral blood and the serum IL-17 level increase in patients with oral squamous cell carcinoma]. AB - Objective To explore the relationships in the numbers of peripheral blood myeloid derived suppressor cells (MDSCs), Th17 cells, and the IL-17 expression in oral squamous cell carcinoma (OSCC) patients. Methods The fasting venous blood specimens of 34 OSCC patients and 16 heacthy donors were collected, OSCC patients includied 18 cases of stage I and stage II and 16 cases of stage III and stage IV. The percentages of MDSCs and Th17 cells were determined by flow cytometry and the serum level of IL-17 was detected by ELISA. Results The percentages of MDSCs and Th17 cells, and the level of IL-17 in OSCC patients were higher than those in healthy donors. In OSCC patients, the percentages of MDSCs and Th17, and the level of IL-17 were higher in stage III and stage IV than in stage I and II. The significant correlation was found between the number of MDSCs and the level of IL 17, while no correlation was found between the numbers of MDSCs and Th17 cells. Conclusion In OSCC patients, the numbers of MDSCs and Th17 cells, and the level of IL-17 increase compared with healthy donors. There is an interaction between DMSCs and Th17 cells. The IL-17 might originate from other innate immunocytes rather than Th17 cells. PMID- 27667468 TI - [STAT3 and NF-kappaB is activated in papillary thyroid carcinoma tissues]. AB - Objective To explore the relationship between signal transducers and activators of transcription 3 (STAT3) and nuclear factor kappaB (NF-kappaB) signaling pathway in papillary thyroid carcinoma. Methods The study enrolled 69 patients with thyroid cancer and 58 control individuals. Real-time fluorescence quantitative PCR, ELISA and immunohistochemistry were separately used to detect mRNA and protein expressions of NF-kappaB and STAT3 in normal thyroid and thyroid carcinoma tissues. Results Compared with normal thyroid tissues, both mRNA and protein expressions of NF-kappaB and STAT3 increased significantly in thyroid carcinoma tissues. Immunohistochemistry showed that the positive rate of STAT3 in all patients with thyroid cancer (89.3%) was significantly higher than that in the patients with normal thyroid tissue (10.2%). Conclusion The function of NF kappaB pathway mediated by STAT3 is activated in patients with thyroid cancer. PMID- 27667469 TI - [Identification and characterization of monoclonal antibody Y4F11 against human B7-H3]. AB - Objective To generate mouse anti-human monoclonal antibodies against the molecules expressed on immune cells from malignant pleural effusions, and identify the antigen recognized by the monoclonal antibody named Y4F11. Methods The cells separated from pleural effusions of lung cancer patients were used to immunize BALB/c mice. Hybridoma technology was used for cell fusion and screening; the monoclonal antibody named Y4F11 was chosen as the object for the following experiment. Flow cytometry was performed to analyze the molecules expressed on naive and activated T, B, NK cells and monocytes; Co immunoprecipitation was conducted to get the antigen pulled down by Y4F11. Mass spectrometry sequencing and BLASTP were used to identify the antigen molecules. Western blotting, dot-blotting and flow cytometry were utilized to identify Y4F11. Results The study obtained 78 hybridoma clones secreting antibodies stably which could recognize surface molecules on cells from pleural effusions. The hybridoma named Y4F11 was chosen as the following experiment object for further identification. The molecule which Y4F11 recognized was about 50 Kd, and further was confirmed as B7-H3 molecule. Furthermore, Y4F11 could recognize B7-H3 expressed on B7-H3 gene-transferred cells as well as B7-H3 fusion protein. Besides, the expression pattern of B7-H3 on immune cells was confirmed by Y4F11 antibody. All these results indicated that the antigen molecule recognized by Y4F11 antibody was B7-H3. Conclusion A hybridoma cell line with stable expression of monoclonal antibody B7-H3 has been successfully obtained and could be used for biological function study on B7-H3. PMID- 27667470 TI - [Prokaryotic expression and antiserum preparation for major antigenic epitope region of major capsid protein of Chinese giant salamander (Andrias davidianus) iridovirus]. AB - Objective To express the fusion protein of major antigenic epitope region of major capsid protein (MCP) of Chinese giant salamander (Andrias davidianus) iridovirus (CGSIV) and prepare the rabbit antiserum. Methods Using the genomic DNA of CGSIV Lueyang strain (CGSIV-LY) as a template, the gene fragment of major antigenic epitope region of MCP was amplified by PCR and cloned into the prokaryotic vector pET-21a(+) to construct the prokaryotic expression recombinant plasmid pET-21a-MCP. The recombinant plasmid was transformed into Escherichia coli BL21(DE3). His-tagged fusion protein was induced by IPTG. After identified by SDS-PAGE and Western blot analysis, the recombinant protein was purified by nitrilotriacetic acid (Ni-NTA) agarose resin. New Zealand rabbits were immunized with the purified recombinant protein to generate antiserum. Specificity and titer of the antiserum were determined by Western blotting and indirect ELISA, and then the antiserum was used to detect the CGSIV in the infected EPC cells by indirect immunofluorescence assay. Results The recombinant protein with the relative molecular mass of 29 000 was expressed. The prepared rabbit antiserum had a good specificity and a high titer. Indirect immunofluorescence assay showed that the antiserum could recognize CGSIV in the infected EPC cells. Conclusion The fusion protein of major antigenic epitope region of MCP of CGSIV is successfully expressed and the rabbit antiserum with a high titer and a good specificity been prepared. PMID- 27667472 TI - A Novel Nanoporous Graphite Based on Graphynes: First-Principles Structure and Carbon Dioxide Preferential Physisorption. AB - Ubiquitous graphene is a stricly 2D material representing an ideal adsorbing platform due to its large specific surface area as well as its mechanical strength and resistance to both thermal and chemical stresses. However, graphene as a bulk material has the tendency to form irreversible agglomerates leading to 3D graphitic structures with a significant decrease of the area available for adsorption and no room for gas intercalation. In this paper, a novel nanoporous graphite formed by graphtriyne sheets is introduced; its 3D structure is theoretically assessed by means of electronic structure and molecular dynamics computations within the DFT level of theory. It is found that the novel layered carbon allotrope is almost as compact as pristine graphite but the inherent porosity of the 2D graphyne sheets and its relative stacking leads to nanochannels that cross the material and whose subnanometer size could allow the diffusion and storage of gas species. A molecular prototype of the nanochannel is used to accurately determine first-principles adsorption energies and enthalpies for CO2, N2, H2O, and H2 within the pores. The proposed porous graphite presents no significant barrier for gas diffusion and shows a high propensity for CO2 physisorption with respect to the other relevant components in both pre- and postcombustion gas streams. PMID- 27667471 TI - The Assessment of Risk in Cardiothoracic Intensive Care (ARCtIC): prediction of hospital mortality after admission to cardiothoracic critical care. AB - The models used to predict outcome after adult general critical care may not be applicable to cardiothoracic critical care. Therefore, we analysed data from the Case Mix Programme to identify variables associated with hospital mortality after admission to cardiothoracic critical care units and to develop a risk-prediction model. We derived predictive models for hospital mortality from variables measured in 17,002 patients within 24 h of admission to five cardiothoracic critical care units. The final model included 10 variables: creatinine; white blood count; mean arterial blood pressure; functional dependency; platelet count; arterial pH; age; Glasgow Coma Score; arterial lactate; and route of admission. We included additional interaction terms between creatinine, lactate, platelet count and cardiac surgery as the admitting diagnosis. We validated this model against 10,238 other admissions, for which the c index (95% CI) was 0.904 (0.89 0.92) and the Brier score was 0.055, while the slope and intercept of the calibration plot were 0.961 and -0.183, respectively. The discrimination and calibration of our model suggest that it might be used to predict hospital mortality after admission to cardiothoracic critical care units. PMID- 27667473 TI - Long non-coding RNAs and genes contributing to the generation of cancer stem cells in hepatocellular carcinoma identified by RNA sequencing analysis. AB - Cancer stem cells (CSCs) play important roles in cancer initiation, progression and metastasis. The aim of the present study was to identify the potential targets that may contribute to the generation of hepatocellular carcinoma stem cells (HCSCs) from hepatocellular carcinoma (HCC) cells. The RNA sequencing (RNA Seq) dataset GSE70537 was downloaded from the Gene Expression Omnibus (GEO) database. Raw RNA sequences were mapped to the GRCh37/hg19 genome based on TopHat and assembled through Cufflinks. Cuffdiff of Cufflinks was used for the screening of differentially expressed genes (DEGs) in the two types of HCSCs (Hep3B-C and Huh7-C) compared with the two types of HCC cells (Hep3B and Huh7) which were satisfied by the criteria of |log2(RPKMHCSC/RPKMHCC)| >1 and p<0.05. In addition, based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID), we screened the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways which were enriched in the DEGs. For the DEGs with consistent differential expression in the two lists of DEGs, the LncRNA2Target database was used for the identification of long non-coding RNA (lncRNA)-gene pairs. A total of 218 and 591 DEGs were identified for the Hep3B-C and Huh7-C samples, respectively, and 22 overlaps were obtained. Biological processes and pathways related to steroid biosynthesis/metabolism or other substance transport were found to be enriched in the two lists of DEGs. Among the 22 overlaps, 16 were found to be consistently differentially expressed in the two HCSC samples, and the lncRNA-gene regulatory network of these genes was constructed. Moreover, several potential biomarkers that may play important roles in the transformation of HCSCs were identified in the regulation network. Through the bioinformatics analysis of the RNA-Seq dataset, several novel targets that were associated with the progression of HCC were obtained, and these targets may be valuable for the treatment and prognosis of HCC. PMID- 27667474 TI - Wogonin enhances intracellular adiponectin levels and suppresses adiponectin secretion in 3T3-L1 adipocytes. AB - As an insulin sensitizer and modulator of inflammatory responses, adiponectin has become a therapeutic target for insulin resistance, diabetes, and diabetes related complications. Wogonin possesses anti-oxidative, anti-inflammatory, and anti-diabetic abilities. However, its effect on generation and secretion of adiponectin is ill-defined in adipocytes. Here, we demonstrated that wogonin administration augmented intracellular adiponectin levels and attenuated adiponectin release in a dose- and time-dependent manner in mature 3T3-L1 adipocytes, along with a suppression of PKCdelta phosphorylation. Wogonin treatment also prevented PKCdelta overexpression-induced reduction of intracellular adiponectin levels and enhancement of adiponectin release. In addition, wogonin supplementation dramatically increased AMPK phosphorylation and SirT1 expression. Inhibition of either AMPK or SirT1 mitigated wogonin action on adiponectin production and release. Furthermore, inhibition of AMPK by its specific inhibitor markedly reduced wogonin-enhanced mRNA and protein expressions of SirT1. These results suggested that wogonin regulated expression and secretion of adiponectin via PKCdelta/AMPK/SirT1 signaling pathway in mature 3T3-L1 adipocytes. PMID- 27667475 TI - A possible reason for the low reproducibility of malondialdehyde determinations in biological samples. PMID- 27667476 TI - Replacing, reducing and refining the use of animals in tuberculosis vaccine research. AB - Tuberculosis (TB) remains a serious global health threat and an improved vaccine is urgently needed. New candidate TB vaccines are tested using preclinical animal models such as mice, guinea pigs, cattle and non-human primates. Animals are routinely infected with virulent Mycobacterium tuberculosis (Mtb) in challenge experiments to evaluate protective efficacy, raising ethical issues regarding the procedure of infection itself, symptoms of disease and humane end-points. We summarize the importance and limitations of animal models in TB vaccine research and review current alternatives and modifications in the context of the NC3Rs framework for replacing, reducing and refining the use of animals for scientific purposes. PMID- 27667478 TI - Spatial variation of fixed charge density in knee joint cartilage from sodium MRI - Implication on knee joint mechanics under static loading. AB - The effects of fixed charge density (FCD) and cartilage swelling have not been demonstrated on cartilage mechanics on knee joint level before. In this study, we present how the spatial and local variations of FCD affects the mechanical response of the knee joint cartilage during standing (half of the body weight, 13 minutes) using finite element (FE) modeling. The FCD distribution of tibial cartilage of an asymptomatic subject was determined using sodium (23Na) MRI at 7T and implemented into a 3-D FE-model of the knee joint (Subject-specific model, FCD: 0.18+/-0.08 mEq/ml). Tissue deformation in the Subject-specific model was validated against experimental, in vivo loading of the joint conducted with a MR compatible compression device. For comparison, models with homogeneous FCD distribution (homogeneous model) and FCD distribution obtained from literature (literature model) were created. Immediately after application of the load (dynamic response), the variations in FCD had minor effects on cartilage stresses and strains. After 13 minutes of standing, the spatial and local variations in FCD had most influence on axial strains. In the superficial tibial cartilage in the Subject-specific model, axial strains were increased up to +13% due to smaller FCD (mean -11%), as compared to the homogeneous model. Compared to the literature model, those were decreased up to -18% due to greater FCD (mean +7%). The findings demonstrate that the spatial and local FCD variations in cartilage modulates strains in knee joint cartilage. Thereby, the results highlight the mechanical importance of site-specific content of proteoglycans in cartilage. PMID- 27667477 TI - Tensile properties of the hip joint ligaments are largely variable and age dependent - An in-vitro analysis in an age range of 14-93 years. AB - INTRODUCTION: Hip joint stability is maintained by the surrounding ligaments, muscles, and the atmospheric pressure exerted via these structures. It is unclear whether the ligaments are capable of preventing dislocation solely due to their tensile properties, and to what extent they undergo age-related changes. This study aimed to obtain stress-strain data of the hip ligaments over a large age range. METHODS: Stress-strain data of the iliofemoral (IL), ischiofemoral (IS) and pubofemoral ligament (PF) were obtained from cadavers ranging between 14 and 93 years using a highly standardized setting. Maximum strains were compared to the distances required for dislocation. RESULTS: Elastic modulus was 24.4 (IL), 22.4 (IS) and 24.9N/mm2 (PF) respectively. Maximum strain was 84.5%, 86.1%, 72.4% and ultimate stress 10.0, 7.7 and 6.5N/mm2 for the IL, IS and PF respectively. None of these values varied significantly between ligaments or sides. The IS' elastic modulus was higher and maximum strain lower in males. Lower elastic moduli of the PF and higher maximum strains for the IS and PF were revealed in the >=55 compared to the <55 population. Maximum strain exceeded the dislocation distance of the IS without external hip joint rotation in females, and of the IS and cranial IL under external rotation in both genders. DISCUSSION: Tensile and failure load properties of the hip joint ligaments are largely variable. The IS and PF change age-dependently. Though the hip ligaments contribute to hip stability, the IS and cranial IL may not prevent dislocation due to their elasticity. PMID- 27667479 TI - Client history and violence on direct care workers in the home care setting. AB - BACKGROUND: Health care workers providing home care are frequently unaware of their client's history of violence or mental illness/substance abuse disorder, recognized risk factors for workplace violence. This study estimated the associations between these factors and experiencing client violence among direct care workers in the home settings (DCWHs). METHODS: Acts and threats of violence were estimated using data from an anonymous survey among DCWHs (n = 876) working at two large home care agencies. Logistic regressions were performed to produce odds ratios. RESULTS: Physical acts and physical or verbal threats of client violence were associated with providing homecare to clients with a violence history (adjusted ORs = 6.60 and 10.78, respectively), whereas threats of client violence (adjusted OR = 5.80) were associated with caring for clients with a mental illness/substance abuse disorder. CONCLUSIONS: Policy and practices that support the communication of appropriate client risk information may reduce the likelihood of workplace violence among DCWHs. Am. J. Ind. Med. 59:1130-1135, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27667480 TI - Integrated analysis of DNA methylation and RNA-sequencing data in Down syndrome. AB - Down syndrome (DS) is the most common birth defect in children. To investigate the mechanisms of DS, the present study analyzed the bisulfite-sequencing (seq) data GSE42144, which was downloaded from the Gene Expression Omnibus. GSE42144 included DNA methylation data of three DS samples and three control samples, and RNA-seq data of two DS samples and five control samples. The methylated sites in the bisulfite-seq data were detected using Bismark and Bowtie2. The BiSeq tool was applied to determine differentially methylated regions and to identify adjacent genes. Using the Database for Annotation, Visualization and Integrated Discovery, the functions of the abnormal demethylated genes were predicted by functional enrichment analyses. Differentially expressed genes (DEGs) were then screened using a paired t-test. Furthermore, the interactions of the proteins encoded by selected genes were determined using the Search Tool for the Retrieval of Interacting Genes, and a protein-protein interaction (PPI) network was constructed using Cytoscape. A total of 74 CpG regions showed significant differential DNA methylation between the DS and normal samples. There were five abnormal demethylated DNA regions in chromosome 21. In the DS samples, a total of 43 adjacent genes were identified with demethylation in their promoter regions and one adjacent gene was identified with upregulated methylation in its promoter regions. In addition, 584 upregulated genes were identified, including 24 genes with transcriptional regulatory function. In particular, upregulated Runt-related transcription factor 1 (RUNX1) was located on chromosome 21. Functional enrichment analysis indicated that inhibitor of DNA binding 4 (ID4) was involved in neuronal differentiation and transcriptional suppression. In the PPI network, genes may be involved in DS by interacting with others, including nuclear receptor subfamily 4 group A member 2 (NR4A2)-early growth response (EGR)2 and NR4A2-EGR3. Therefore, RUNX1, NR4A2, EGR2, EGR3 and ID4 may be key genes associated with the pathogenesis of DS. PMID- 27667481 TI - Investigating the Molecular Mechanisms Behind Uncharacterized Cysteine Losses from Prediction of Their Oxidation State. AB - Cysteines are among the rarest amino acids in nature, and are both functionally and structurally very important for proteins. The ability of cysteines to form disulfide bonds is especially relevant, both for constraining the folded state of the protein and for performing enzymatic duties. But how does the variation record of human proteins reflect their functional importance and structural role, especially with regard to deleterious mutations? We created HUMCYS, a manually curated dataset of single amino acid variants that (1) have a known disease/neutral phenotypic outcome and (2) cause the loss of a cysteine, in order to investigate how mutated cysteines relate to structural aspects such as surface accessibility and cysteine oxidation state. We also have developed a sequence based in silico cysteine oxidation predictor to overcome the scarcity of experimentally derived oxidation annotations, and applied it to extend our analysis to classes of proteins for which the experimental determination of their structure is technically challenging, such as transmembrane proteins. Our investigation shows that we can gain insights into the reason behind the outcome of cysteine losses in otherwise uncharacterized proteins, and we discuss the possible molecular mechanisms leading to deleterious phenotypes, such as the involvement of the mutated cysteine in a structurally or enzymatically relevant disulfide bond. PMID- 27667483 TI - Localized lichen myxedematosus in childhood: what is the accurate diagnosis? PMID- 27667482 TI - Modeling oblong proteins and water-mediated interfaces with RosettaDock in CAPRI rounds 28-35. AB - The 28th-35th rounds of the Critical Assessment of PRotein Interactions (CAPRI) served as a practical benchmark for our RosettaDock protein-protein docking protocols, highlighting strengths and weaknesses of the approach. We achieved acceptable or better quality models in three out of 11 targets. For the two alpha repeat protein-green fluorescent protein (alpharep-GFP) complexes, we used a novel ellipsoidal partial-global docking method (Ellipsoidal Dock) to generate models with 2.2 A/1.5 A interface RMSD, capturing 49%/42% of the native contacts, for the 7-/5-repeat alpharep complexes. For the DNase-immunity protein complex, we used a new predictor of hydrogen-bonding networks, HBNet with Bridging Waters, to place individual water models at the complex interface; models were generated with 1.8 A interface RMSD and 12% native water contacts recovered. The targets for which RosettaDock failed to create an acceptable model were typically difficult in general, as six had no acceptable models submitted by any CAPRI predictor. The UCH-L5-RPN13 and UCH-L5-INO80G de-ubiquitinating enzyme-inhibitor complexes comprised inhibitors undergoing significant structural changes upon binding, with the partners being highly interwoven in the docked complexes. Our failure to predict the nucleosome-enzyme complex in Target 95 was largely due to tight constraints we placed on our model based on sparse biochemical data suggesting two specific cross-interface interactions, preventing the correct structure from being sampled. While RosettaDock's three successes show that it is a state-of-the-art docking method, the difficulties with highly flexible and multi-domain complexes highlight the need for better flexible docking and domain assembly methods. Proteins 2017; 85:479-486. (c) 2016 Wiley Periodicals, Inc. PMID- 27667484 TI - Development of a Double-Antigen Microsphere Immunoassay for Simultaneous Group and Serotype Detection of Bluetongue Virus Antibodies. AB - Bluetongue viruses (BTV) are arboviruses responsible for infections in ruminants. The confirmation of BTV infections is based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs) using the BTV viral protein 7 (VP7) as antigen. The determination of the BTV serotype by serological analyses could be only performed by neutralization tests (VNT) which are time-consuming and require BSL3 facilities. VP2 protein is considered the major serotype-defining protein of BTV. To improve the serological characterization of BTV infections, the recombinant VP7 and BTV serotype 8 (BTV-8) VP2 were synthesized using insect cells expression system. The purified antigens were covalently bound to fluorescent beads and then assayed with 822 characterized ruminant sera from BTV vaccinations or infections in a duplex microsphere immunoassay (MIA). The revelation step of this serological duplex assay was performed with biotinylated antigens instead of antispecies conjugates to use it on different ruminant species. The results demonstrated that MIA detected the anti-VP7 antibodies with a high specificity as well as a competitive ELISA approved for BTV diagnosis, with a better efficiency for the early detection of the anti-VP7 antibodies. The VP2 MIA results showed that this technology is also an alternative to VNT for BTV diagnosis. Comparisons between the VP2 MIA and VNT results showed that VNT detects the anti-VP2 antibodies in an early stage and that the VP2 MIA is as specific as VNT. This novel immunoassay provides a platform for developing multiplex assays, in which the presence of antibodies against multiple BTV serotypes can be detected simultaneously. PMID- 27667486 TI - [Anti-NMDA Receptor Antibody-Related Encephalitis]. AB - Recently, the search for diagnostic antibody markers has drawn considerable attention in relation to autoimmune encephalitis. Among the antibody markers, the most frequently detected is the anti-N-methyl-D-aspartate receptor (NMDAR)antibody. Patients with this antibody develop characteristic clinical features. This disease tends to affect young women, and starts with psychiatric symptoms followed by seizures, involuntary movements, autonomic failure, and respiratory failure. Nearly half of these female patients have ovarian teratoma. Some of the patients with anti-NMDAR antibody show atypical clinical features. Approximately 4% show only psychiatric symptoms, which might lead to a diagnosis of malignant catatonia. Other reports describe patients experiencing refractory seizures to have the anti-NMDAR antibody. Some of the antibody-positive patients are associated with demyelinating disorders, and some develop anti-NMDAR encephalitis after recovery from herpes simplex encephalitis. It is important to test the anti-NMDAR antibody in these groups since immunotherapy ameliorates their symptoms. The anti-NMDAR antibody binds to the constitutional epitope at the extracellular domain of GluN1 and disrupts its function. Early introduction of immunotherapy together with tumor resection will results in improvement of neurological symptoms. PMID- 27667487 TI - [Voltage-Gated Potassium Channel-Complex Antibodies Associated Encephalopathy and Related Diseases]. AB - Voltage-gated potassium channel (VGKC) complex antibodies are auto-antibodies, initially identified in acquired neuromyotonia (aNMT; Isaacs' syndrome), which cause muscle cramps and difficulty in opening the palm of the hands. Subsequently, these antibodies were found in patients presenting with aNMT along with psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) patient with prominent amnesia and frequent seizures. Typical LE cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures (FBDS). The VGKC complex is a group of proteins that are strongly associated in situ and after extraction in the mild detergent digitonin. Recent studies indicated that the VGKC complex antibodies are mainly directed toward associated proteins (for example LGI1, Caspr2) that complex with VGKCs themselves. Patients with aNMT or MoS are most likely to have Caspr2 antibodies, whereas LGI1 antibodies are found characteristically in patients with FBDS and LE. We systematically identified and quantified autoantibodies in patient sera with VGKC-complex antibody associated encephalopathy and showed the relationship between individual antibodies and patient's symptoms. Furthermore, we revealed how autoantibodies disrupt the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, reducing the synaptic AMPA receptors. PMID- 27667485 TI - Functional pharmacological characterization of SER100 in cardiovascular health and disease. AB - BACKGROUND AND PURPOSE: SER100 is a selective nociceptin (NOP) receptor agonist with sodium-potassium-sparing aquaretic and anti-natriuretic activity. This study was designed to characterize the functional cardiovascular pharmacology of SER100 in vitro and in vivo, including experimental models of cardiovascular disease. EXPERIMENTAL APPROACH: Haemodynamic, ECG parameters and heart rate variability (HRV) were determined using radiotelemetry in healthy, conscious mice. The haemodynamic and vascular effects of SER100 were also evaluated in two models of cardiovascular disease, spontaneously hypertensive rats (SHR) and murine hypoxia induced pulmonary hypertension (PH). To elucidate mechanisms underlying the pharmacology of SER100, acute blood pressure recordings were performed in anaesthetized mice, and the reactivity of rodent aorta and mesenteric arteries in response to electrical- and agonist-stimulation assessed. KEY RESULTS: SER100 caused NOP receptor-dependent reductions in mean arterial blood pressure and heart rate that were independent of NO. The hypotensive and vasorelaxant actions of SER100 were potentiated in SHR compared with Wistar Kyoto. Moreover, SER100 reduced several indices of disease severity in experimental PH. Analysis of HRV indicated that SER100 decreased the low/high frequency ratio, an indicator of sympatho-vagal balance, and in electrically stimulated mouse mesenteric arteries SER100 inhibited sympathetic-induced contractions. CONCLUSIONS AND IMPLICATIONS: SER100 exerts a chronic hypotensive and bradycardic effects in rodents, including models of systemic and pulmonary hypertension. SER100 produces its cardiovascular effects, at least in part, by inhibition of cardiac and vascular sympathetic activity. SER100 may represent a novel therapeutic candidate in systemic and pulmonary hypertension. PMID- 27667488 TI - [Clinical Features and Treatment of Hashimoto Encephalopathy]. AB - Hashimoto encephalopathy (HE) is characterized by heterogeneous neurological symptoms. HE is diagnosed based on three criteria-the presence of antithyroid antibodies, neurological symptoms from the cerebrum and/or cerebellum, and a positive response to immunotherapy. We clinically analyzed 18 patients (3 men, 15 women; age range, 38-81years) diagnosed with HE in our hospital from May 2013 to January 2016. Eleven patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or neuralgia. Surprisingly, the majority of the pain was distributed in a manner that was not explainable anatomically. Seventeen patients showed motor disturbances, such as weakness, paresis of extremities, or dexterity movement disorder, and eight patients showed give-way weakness, which is disruption of continuous muscle contraction. Other symptoms indicative of brain-related anomalies such as tremor, dystonia, involuntary movements, cerebellar ataxia, parkinsonism, memory loss, and chronic fatigue were also seen. In most patients, such motor, sensory, or higher brain functions were markedly improved with immunosuppressive therapies such as prednisolone, azathioprine, or immunoadsorption therapy. Although give-way weakness and anatomically unexplainable pain are typically considered as being psychogenic in origin, the presence of these symptoms is indicative of HE. HE exhibits diffuse involvement of the entire brain and thus, these symptoms are explainable. We propose that physicians should not diagnose somatoform disorders without first excluding autoimmune encephalopathy. PMID- 27667489 TI - [Neuropsychiatric Systemic Lupus Erythematosus]. AB - Central nervous system damage, a major organ manifestation of systemic lupus erythematosus (SLE), causes significant morbidity and mortality. Designating this condition as neuropsychiatric SLE (NPSLE), the American College of Rheumatology defines it as involving the central and peripheral nervous systems and being characterized by various manifestations including stroke, seizures, and psychosis. NPSLE treatment mainly seeks to reduce damage accrual. In patients with NPSLE, the use of high-dose corticosteroids is recommended in combination with immunosuppressants, such as mycophenolate mofetil and intravenous cyclophosphamide pulse therapy. This can be accomplished by controlling the activity of the disease, minimizing the use of corticosteroids, and optimizing the management of comorbidities, including cardiovascular risk factors. An international task force analysis of a treat-to-target strategy for SLE (T2T/SLE) recommended targeting remission, preventing damage, and improving quality of life. Thus, more effective and less toxic treatments, such as those using biologics or kinase inhibitors, are still being developed for the treatment of SLE/NPSLE. PMID- 27667490 TI - [Autoimmune Encephalitis Associated with Malignant Tumors]. AB - Autoimmune encephalitis consists of limbic symptoms and signs associated with antibodies against neuronal cell-surface antigens or intracellular antigens. Some cases are known to be associated with anti-channel or anti-receptor-related molecule antibodies. Whether these cases are paraneoplastic depends on the kinds of antigens that the antibodies are produced against. Other cases due to well characterized onco-neural antibodies are almost always paraneoplastic and are generally resistant to anti-tumor therapy and/or immunotherapy. An exception is anti-Ma2 antibody-positive encephalitis associated with a testicular tumor. Antibodies for intracellular antigens are considered not to be pathogenic. Rather, the T-cell response is thought to be responsible. These antibodies are useful markers for the diagnosis of paraneoplastic disorders and in the search for underlying cancer, as neurological symptoms often precede tumor diagnosis. There is a relationship among onco-neural antibodies, clinical features, tumor types, and response to immunotherapy. Here we describe the characteristics of autoimmune encephalitis cases with antibodies against different intracellular antigens, such as Hu, Ma2, CRMP5, or amphiphysin. PMID- 27667491 TI - [CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids)]. AB - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) has been recently identified as an inflammatory central nervous system (CNS) disorder. Punctate and curvilinear gadolinium enhancement (peppering) the pons is a characteristic magnetic resonance imaging (MRI) feature of CLIPPERS. Pathogenesis of this disorder remains unknown. A specific serum or cerebrospinal fluid biomarker for this disorder is currently unknown. Whether CLIPPERS is an actual new disease or just represents overlapping symptoms from multiple diseases is still debated. Many differential diagnoses exist even when using imaging as a tool. Pre-lymphoma states, such as grade I LYG (lymphomatoid granulomatosis) and sentinel lesions of primary CNS lymphoma are the most difficult to distinguish. PMID- 27667492 TI - [Causative Genes for Amyotrophic Lateral Sclerosis]. AB - About 20 causative genes were reported for amyotrophic lateral sclerosis. Using next generation sequencer, new genes have been sequentially reported. These genes' products are thought to be involved in the pathologic mechanism of ALS. The pathophysiology is investigated and disease characteristics are discussed according to the causative genes. In addition, genetic counseling is recommended when genetic diagnosis is attempted. PMID- 27667493 TI - [Patients' Perspective on Parkinson Disease Therapies: Comparative Results of Large-scale Surveys in 2008 and 2013 in Japan]. AB - A large-scale patient survey was conducted in 2013 and results compared with those of a similar scale survey conducted in 2008 to clarify the current status of drug therapy and patients' understanding of Parkinson disease (PD) and therapy. A total of 4,278 and 101 patients respectively participated in primary mail survey and secondary interview surveys. Measures of PD severity, activity level, and level of assistance required in daily life were improved compared with those in the 2008 survey. Average daily dose of levodopa was increased across all disease durations. The treatment compliance rate of monoamine oxidase-B inhibitors was increased in patients with < 6 years of disease duration, but was reduced in patients with >= 6 years. The treatment compliance rates of catechol-O methyltransferase inhibitors and zonisamide were increased. Patients with experience of dyskinesia hoped more to improve their mobility rather than avoid dyskinesia. Since there is no fundamental treatment for PD and drug therapy achieves only symptomatic relief, PD exerted a negative influence on patients' satisfaction. The patients' unsatisfied feelings changed with the severity of OFF time. Physicians are required to not only devise a selection and dosage of PD therapeutic drugs but also empathetically respond to patients, with consideration of their feelings. (Received January 22, 2016; Accepted April 11, 2016; Published September 1, 2016). PMID- 27667494 TI - [NMDA-GluR Subunit Antibody-Positive Encephalitis: A Clinical Analysis of Five Cases]. AB - Five consecutive cases of anti-NMDA-receptor encephalitis that we encountered were marked by a rapidly fluctuating level of consciousness associated with psychotic and delirious mental states. Opisthotonus, catatonia, and rhythmic and non-rhythmic involuntary movements of the mouth and jaw were also characteristic features of these particular cases. Serious and potentially fatal problems included epilepsia partialis continua, partial and generalized seizures, and respiratory depression, resembling the symptoms of encephalitis lethargica. An epidemic of encephalitis lethargica, also known of Economo encephalitis, occurred around 1917. Magnetic resonance imaging revealed edema of the neocortex in two cases and electroencephalography showed polymorphic and monomorphic delta slowing in the acute stage, although electroencephalographic seizure activity were not apparent. Routine cerebrospinal fluid analyses revealed lymphocyte-dominant pleocytosis in three cases, but antibodies against the NMDA-GluR subunit, GluN2B N-terminal, were at a high level in the fluid. All patients recovered without apparent sequelae. Two patients found to have ovarian teratoma underwent surgery for tumor removal. Treatments included pulse intravenous methylprednisolone, high dose immunoglobulin, and plasma exchange together with seizure control and respiratory support. However, rituximab and or cyclophosphamide pulse therapy should also be considered for intractable cases, as indicated by recent reports. (Received February 16, 2016; Accepted May 2, 2016; Published September 1, 2016). PMID- 27667495 TI - Sensitised LnIII Emission and Excited-State Dynamics of Cofacial 'Pacman' Porphyrin Terpyridine Complexes. AB - An asymmetric 'Pacman' metalloligand, [Zn(PXT)], which features a cofacial ZnII porphyrin unit (P) covalently attached to a terpyridine (T) chelating group via a rigid xanthene (X) moiety has been prepared, and its interactions with several different trivalent LnIII cations (NdIII , GdIII , YbIII and LuIII ) have been examined. The formation of 1:1 metal-ligand complexes was monitored by 1 H NMR spectroscopy and corroborated by HRMS data. Solution-stability constants were determined by UV/Vis titration, and the resulting complexes with NdIII or YbIII demonstrated sensitised emission in the NIR region due to energy transfer from the ZnII -porphyrin donor to LnIII acceptor. The energy transfer was investigated by transient absorption techniques, which provided insight into the kinetics and efficiency of the antenna effect. PMID- 27667496 TI - Identification of a novel allele, HLA-A*26:01:01:03N, by full-length genome sequencing. AB - The HLA-A*26:01:01:03N allele shows a single nucleotide difference compared with HLA-A*26:01:01:01 in intron 4(1846 G>A). PMID- 27667497 TI - A population-based longitudinal study on the implications of demographics on future blood supply. AB - BACKGROUND: Changes in demographics with increases in older age groups and decreases in younger age groups imply an increased demand for blood transfusions paralleled by a decrease in the population eligible for blood donation. However, more restrictive transfusion triggers and the patient blood management initiative also reduce the demand for red blood cells (RBCs). Eastern Germany is a model region for the impact of demographic changes, which manifest in this region approximately 10 years earlier than in other regions due to the 50% birth rate decline after 1989. STUDY DESIGN AND METHODS: We report the 2010 longitudinal 5 year follow-up of the study assessing all whole blood donations and RBC transfusions in Mecklenburg-West Pomerania. We compared the projections that were made 5 years ago with: 1) the current age structure of the blood donor and transfusion recipient populations and 2) its impact on blood demand and blood donation numbers in specific age groups. RESULTS: Transfusion rates were lower and blood donation rates were higher than predicted in 2005. Although transfusion rates/1000 decreased in nearly all age groups, the overall annual transfusion rate increased to 66.4 RBC units/1000 (in 2005, 62.2/1000) due to the absolute increase in the elderly population. Despite a 7.4% decline in the population 18 to 65 years of age, whole blood donations increased by 11.7% between 2005 and 2010, but thereafter decreased by 21% (first-time donors by 39.4%), reflecting the effect of the post-1990 birth rate decline on the donor population. CONCLUSION: Changes in demography and medical practice impact the delicate balance between available blood supply and potential future transfusion needs. In times of pronounced demographic changes, regular monitoring of the blood demand and age structure of blood recipients and donors is required to allow strategic planning to prevent blood shortages or overproduction. PMID- 27667498 TI - Observation of Quantum Confinement in Monodisperse Methylammonium Lead Halide Perovskite Nanocrystals Embedded in Mesoporous Silica. AB - Hybrid organic-inorganic metal halide perovskites have fascinating electronic properties and have already been implemented in various devices. Although the behavior of bulk metal halide perovskites has been widely studied, the properties of perovskite nanocrystals are less well-understood because synthesizing them is still very challenging, in part because of stability. Here we demonstrate a simple and versatile method to grow monodisperse CH3NH3PbBrxIx-3 perovskite nanocrystals inside mesoporous silica templates. The size of the nanocrystal is governed by the pore size of the templates (3.3, 3.7, 4.2, 6.2, and 7.1 nm). In depth structural analysis shows that the nanocrystals maintain the perovskite crystal structure, but it is slightly distorted. Quantum confinement was observed by tuning the size of the particles via the template. This approach provides an additional route to tune the optical bandgap of the nanocrystal. The level of quantum confinement was modeled taking into account the dimensions of the rod shaped nanocrystals and their close packing inside the channels of the template. Photoluminescence measurements on CH3NH3PbBr clearly show a shift from green to blue as the pore size is decreased. Synthesizing perovskite nanostructures in templates improves their stability and enables tunable electronic properties via quantum confinement. These structures may be useful as reference materials for comparison with other perovskites, or as functional materials in all solid-state light-emitting diodes. PMID- 27667500 TI - The impact of tobacco-free pharmacy policies on smoking prevalence. AB - OBJECTIVES: California and Massachusetts are the only 2 states in the United States with municipalities that have local laws prohibiting the sale of tobacco products by pharmacies. The impacts of the tobacco-free pharmacy laws remain understudied. This study aims to fill this gap by examining the association between tobacco-free pharmacy laws and smoking prevalence among adults over time in California and Massachusetts. DESIGN: This study used a series of cross sectional surveys. The data source for this study was the Behavioral Risk Factor Surveillance Survey for each year from 2005 to 2013. SETTING: The longitudinal changes in smoking prevalence at the city or county level were estimated and comparisons were made between cities or counties with tobacco-free pharmacy laws and those without the laws. PARTICIPANTS: The participants used to estimate smoking prevalence were representative of adults within California and Massachusetts. INTERVENTION: The implementation of tobacco-free pharmacy laws was considered to be the intervention in this study. MAIN OUTCOME MEASURES: The outcome measures were smoking prevalence among adults. Mixed-effects negative binomial models were performed primarily to examine longitudinal changes in outcome measures. RESULTS: The prevalence of smoking decreased in both states over time. In Massachusetts, there was a statistically significant decrease in smoking prevalence among cities with tobacco-free pharmacy laws compared with those without such laws. Despite the presence of an 8.6% decrease in prevalence after the implementation of tobacco-free pharmacy laws, this reduction was not statistically significant after controlling for the negative trend in smoking rates overall and other factors. CONCLUSION: This study evaluated tobacco-free pharmacy laws with regard to the real-world impacts. Our findings highlight the need for future research on the effects of tobacco-free pharmacy laws with a prolonged time span and a comprehensive understanding of the law's implementation and enforcement. PMID- 27667501 TI - Pharmacist engagement within a hepatitis C ambulatory care clinic in the era of a treatment revolution. AB - OBJECTIVES: To describe an innovative hepatitis C virus (HCV) care program and treatment outcomes resulting from pharmacist services. SETTING: Adult ambulatory care HCV clinic within the Miami Veteran Affairs Healthcare System. PRACTICE DESCRIPTION: Pharmacists with limited prescriptive authority are integrated into a medical hepatology care team. PRACTICE INNOVATION: Pharmacists screen patients with HCV infection for treatment eligibility, counsel patients upon treatment initiation, assess ongoing treatment success and toxicity through patient appointments, telephone calls, and the ordering of pertinent laboratory data, and provide oversight of all patients on HCV therapies. Treatment outcomes are reported to the institutional Antimicrobial Stewardship Program. EVALUATION: Data produced from a continuous quality assurance initiative were utilized. Descriptive statistics were used to present data. RESULTS: From January 2014 through September 2015 there were 1619 pharmacist encounters for 532 unique patients and 597 screenings (including 578 approvals) were completed by a pharmacist. During this time 555 patients were initiated on at least 1 HCV treatment course, with 565 total treatment courses initiated. As new agents became available for use, fluctuation in regimen selection was seen. The most commonly prescribed medications were sofosbuvir (46%), ledipasvir/sofosbuvir (37%), and simeprevir (33%). Of the 565 HCV treatment courses initiated, 360 were completed, 29 were stopped early during treatment, and 176 were ongoing. Of the 360 completed courses, 249 had sustained virologic response at week 12 results available, of which 225 (90%) achieved treatment success and 24 (10%) relapsed. Of the 29 courses stopped early, 11 were due to poor medication adherence and 8 were due to adverse drug reaction. CONCLUSION: Through a structured process employing a scope of practice, pharmacists can extend the capacity of medical hepatology providers and provide pharmacotherapy services to enhance care. Information provided here may serve beneficial to others looking to initiate or expand existing HCV pharmacist services. PMID- 27667499 TI - Religiosity, race/ethnicity, and alcohol use behaviors in the United States. AB - BACKGROUND: Religiosity is a protective factor against many health problems, including alcohol use disorders (AUD). Studies suggest that religiosity has greater buffering effects on mental health problems among US Blacks and Hispanics than Whites. However, whether race/ethnic differences exist in the associations of religiosity, alcohol consumption and AUD is unclear. METHOD: Using 2004-2005 NESARC data (analytic n = 21 965), we examined the relationship of public religiosity (i.e. frequency of service attendance, religious social group size), and intrinsic religiosity (i.e. importance of religious/spiritual beliefs) to frequency of alcohol use and DSM-IV AUD in non-Hispanic (NH) Blacks, Hispanics and NH Whites, and whether associations differed by self-identified race/ethnicity. RESULTS: Only public religiosity was related to AUD. Frequency of religious service attendance was inversely associated with AUD (NH Whites beta: 0.103, p 0.05) or Hispanics (beta: -0.002, p > 0.05). CONCLUSIONS: US adults reporting greater public religiosity were at lower risk for AUD. Public religiosity may be particularly important among NH Blacks, while intrinsic religiosity may be particularly important among NH Whites, and among Hispanics who frequently attend religious services. Findings may be explained by variation in drinking-related norms observed among these groups generally, and in the context of specific religious institutions. PMID- 27667503 TI - Molecular profiling of naphthenic acids in technical mixtures and oil sands process-affected water using polar reversed-phase liquid chromatography-mass spectrometry. AB - In this work, a reversed-phase ultra-HPLC (UHPLC) ultrahigh resolution MS (UHRMS) method was evaluated for the comprehensive profiling of NAs containing two O atoms in each molecule (O2NAs; general formula Cn H2n + z O2 , where n is the number of carbon atoms and z represents hydrogen deficiency). Using a polar cyanopropyl-bonded phase column and negative-ion electrospray ionization mass spectrometric detection at 120,000 FWHM (m/z 400), 187 and 226 O2NA species were found in two naphthenic acid technical mixtures, and 424 and 198 species with molecular formulas corresponding to O2NAs were found in two oil sands process affected water samples (one from a surface mining operation and the other from a steam-assisted gravity drainage operation), respectively. To our knowledge, these are the highest numbers of molecular compositions of O2NAs that have been profiled thus far in environmental samples. Assignments were based on accurate mass measurements (<=3 ppm) combined with rational molecular formula generation, correlation of chromatographic behavior of O2NA homologues with their elemental compositions, and confirmation with carboxyl group-specific chemical derivatization using 3-nitrophenylhydrazine. Application of this UHPLC-UHRMS method to the quantitation of O2NAs in the surface mining operation-derived water sample showed excellent linearity (R2 = 0.9999) with external calibration, a linear range of 256-fold in concentration, and quantitation accuracies of 64.9 and 69.4% at two "standard substance" spiking levels. PMID- 27667502 TI - ClpAP is an auxiliary protease for DnaA degradation in Caulobacter crescentus. AB - The Clp family of proteases is responsible for controlling both stress responses and normal growth. In Caulobacter crescentus, the ClpXP protease is essential and drives cell cycle progression through adaptor-mediated degradation. By contrast, the physiological role for the ClpAP protease is less well understood with only minor growth defects previously reported for DeltaclpA cells. Here, we show that ClpAP plays an important role in controlling chromosome content and cell fitness during extended growth. Cells lacking ClpA accumulate aberrant numbers of chromosomes upon prolonged growth suggesting a defect in replication control. Levels of the replication initiator DnaA are elevated in DeltaclpA cells and degradation of DnaA is more rapid in cells lacking the ClpA inhibitor ClpS. Consistent with this observation, ClpAP degrades DnaA in vitro while ClpS inhibits this degradation. In cells lacking Lon, the protease previously shown to degrade DnaA in Caulobacter, ClpA overexpression rescues defects in fitness and restores degradation of DnaA. Finally, we show that cells lacking ClpA are particularly sensitive to inappropriate increases in DnaA activity. Our work demonstrates an unexpected effect of ClpAP in directly regulating replication through degradation of DnaA and expands the functional role of ClpAP in Caulobacter. PMID- 27667504 TI - Case of widespread fat necrosis that was caused by severe pancreatitis and histologically resembled pancreatic panniculitis. PMID- 27667505 TI - The importance of nonstop treatment after delivery for pregnant women with type 2 diabetes. AB - BACKGROUND: There are no reports of very long follow-up studies of pregnant women with type 2 diabetes after delivery. Here we describe cases of Japanese women whom we treated for 20 to 50 years after deliveries to investigate the relationship between blood glucose control and diabetic complications. METHODS: In Japan, the prevalence of type 1 diabetes is very low, and we have very few long-term follow-up cases with type 1 diabetes. Therefore, we chose to describe subjects with type 2 diabetes only. We present data on a total of 80 deliveries, 68 cases, treated by one of us (Y.O.) for more than a 50-year period. They are divided into 4 groups based on duration of treatment after delivery: more than 50 years (1 delivery, 1 patient), 40 to 49 years (13 deliveries, 11 patients), 30 to 39 years (19 deliveries, 16 patients), and 20 to 29 years (47 deliveries, 40 patients). Their present average ages in these 4 groups are 77, 72.4, 65.9, and 55.5 years, respectively. Their average HbA1c levels at last visit, in May 2014, are 8.2%, 7.6%.,7.2%, and 8.3%, respectively. RESULTS: Despite elevated HbA1c levels, they had relatively few complications: 40% (no retinopathy), 43.8% (simple retinopathy), and 12.5% (treated with photocoagulation); 67.5% (no albuminuria), 26.3% (albuminuria), and 6.3% (treated with renal transplantation or hemodialysis). Therefore, even if glycemic control is not ideal, nonstop treatment of Japanese women for type 2 diabetes after deliveries is effective to prevent diabetic complications. CONCLUSIONS: Long-term attention to care of diabetes after pregnancy may be preventive of diabetic complications in other populations as well. PMID- 27667506 TI - Electrophilic RNA for Peptidyl-RNA Synthesis and Site-Specific Cross-Linking with tRNA-Binding Enzymes. AB - RNA functionalization is challenging due to the instability of RNA and the limited range of available enzymatic reactions. We developed a strategy based on solid phase synthesis and post-functionalization to introduce an electrophilic site at the 3' end of tRNA analogues. The squarate diester used as an electrophile enabled sequential amidation and provided asymmetric squaramides with high selectivity. The squaramate-RNAs specifically reacted with the lysine of UDP-MurNAc-pentapeptide, a peptidoglycan precursor used by the aminoacyl transferase FemXWv for synthesis of the bacterial cell wall. The peptidyl-RNA obtained with squaramate-RNA and unprotected UDP-MurNAc-pentapeptide efficiently inhibited FemXWv . The squaramate unit also promoted specific cross-linking of RNA to the catalytic Lys of FemXWv but not to related transferases recognizing different aminoacyl-tRNAs. Thus, squaramate-RNAs provide specificity for cross linking with defined groups in complex biomolecules due to its unique reactivity. PMID- 27667507 TI - Characterization of microparticles in patients with venous malformations of the head and neck. AB - OBJECTIVES: To determine the basic biochemical features of microparticles (MP) in patients with venous malformation (VM) of the head and neck. METHODS: Microparticles were isolated from peripheral venous blood of VM patients or healthy subjects and from lesional fluid of VM patients. Flow cytometry and real time polymerase chain reaction were employed to determine the concentration, cellular origin, and RNA expression of obtained MP. A functional coagulation test was applied to measure the coagulant activity of MP. RESULTS: Circulating levels of total MP, platelet-derived MP, and endothelial MP were significantly elevated in VM patients and were consistently increased in VM patients with more extensive lesions. Lesional MP (MP from lesional fluid of VM) in VM patients were more abundant than circulating MP from VM patients or healthy subjects. Moreover, MP from VM patients displayed markedly distinct mRNA and microRNA expression compared with healthy subjects. Furthermore, MP from VM patients exhibited enhanced procoagulant activity, as evidenced by significantly shorter coagulation time. CONCLUSIONS: This study demonstrates for the first time that patients with VM have an altered MP profile and MP may be associated with VM-associated thrombogenesis. Further studies are required to explore the precise pathophysiological roles of MP in VM. PMID- 27667509 TI - Effects of Angelica dahurica on obesity and fatty liver in mice. AB - Angelica dahurica (A. dahurica) is a traditional Chinese medicinal plant being used in clinical practice. The present study demonstrated that A. dahurica could reduce white-fat weight in high-fat-diet hyperlipidemic mice, decrease total cholesterol and triglyceride concentrations in the livers of both high-fat-diet and Triton WR1339 induced hyperlipidemic mice, and enhance the total hepatic lipase activities of them. These findings were further supported by the results derived from the experiments with HepG2 cells in vitro. In addition, the proteins related to lipids metabolism were investigated using LC-MS/MS, indicating that genes of lipid metabolism and lipid transport were regulated by A. dhurica. The results from LC-MS/MS were further conformed by Western blot and real time PCR assays. A. dahurica could down-regulate the expression of catalase (CAT) and sterol carrier protein2 (SCP2) and up-regulate the expression of lipid metabolism related genes-lipase member C (LIPC) and peroxisome proliferator-activated receptor gamma (PPARgamma). In the Triton WR1339 mouse liver and HepG2 cells in vitro, A. dahurica was able to increase the expression of LIPC and PPARgamma, confirming the results from in vivo experiments. Imperatorin showed the same activity as A. dahurica, suggesting it was one of the major active ingredients of the herb. In conclusion, our work represented a first investigation demonstrating that A. dahurica was able to regulate lipid metabolism and could be developed as a novel approach to fighting against fatty liver and obesity. PMID- 27667508 TI - RAW 264.7 co-cultured with ultra-high molecular weight polyethylene particles spontaneously differentiate into osteoclasts: an in vitro model of periprosthetic osteolysis. AB - Wear-particle osteolysis affects prosthesis survival leading to implant loosening up to 70% of revisions. Therapeutic strategies are increasing, however alternative testing methods to experimentally evaluate such treatments are lacking. The aim of this study was to reproduce an in vitro osteolysis model recapitulating the events that, starting from the exposure of macrophages to polyethylene, lead to the establishment of osteoclastogenesis and inflammation. Responses to polyethylene, at 3 and 7 days, in a macrophage cell line, RAW 264.7, were determined by DNA quantification, immunofluorescence, pit assay, gene expression, cytokine production and NF-kB activation. Results showed that 3 days exposure to particles could induce a significant production of Tumor Necrosis Factor alpha (p < 0.0005) and Prostaglandin E2 (p < 0.005) compared to controls. Particles also induced macrophages to spontaneously differentiate into mature and active osteoclasts, in terms of identification of multinucleated cells by Phalloidin staining and by the analysis of osteoclast-specific gene markers. In particular, at 3 days polyethylene induced a significant up-regulation of Nuclear Factor of Activated T-cells, cytoplasmic 1, Receptor Activator of Nuclear factor Kappa-B and Receptor Activator of Nuclear Factor Kappa-B Ligand genes (p < 0.0005) compared to controls. At protein level, the particles induced a significant increase of Receptor Activator of Nuclear Factor Kappa-B Ligand at day 7 over controls (p < 0.0005). Osteoclasts were capable to resorb bone even in absence of differentiating factors. The possible mechanism, beside spontaneous osteoclastogenesis mediated by wear debris, was identified in an autocrine up regulation of Receptor activator of nuclear factor kappa-B ligand gene expression and protein synthesis. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 510-520, 2017. PMID- 27667510 TI - Pharmacodynamic study on insomnia-curing effects of Shuangxia Decoction in Drosophila melanogaster. AB - The present study aimed to establish a pharmacodynamic method using the pySolo software to explore the influence of freeze-dried powders of Shuangxia Decoction (SXD) on the sleep of normal Drosophila melanogaster and the Drosophila melanogaster whose sleep was divested by light. The dose-effect and the time effect relationships of SXD on sleep were examined. The effect-onset concentration of SXD was 0.25%, the plateau appeared at the concentration of 2.5% and the total sleep time showed a downtrend when the concentration was greater than 2.5%. The sleep time was the longest on the fourth day after SXD was given. The fruit fly sleep deprivation model was repeated by light stimulation at night. The middle dosage group (2.5%) had the best insomnia-curing effect. In conclusion, using the pySolo software, an approach for the pharmacodynamics study was established with Drosophila melanogaster as a model organism to determine the insomnia-curing effects of the traditional Chinese medicine (TCM). Our results demonstrated the reliability of this method. The freeze-dried powders of SXD could effectively improve the sleep quality of Drosophila melanogaster. PMID- 27667511 TI - Phenolic acids isolated from the fungus Schizophyllum commune exert analgesic activity by inhibiting voltage-gated sodium channels. AB - The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3 hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant (TTX-r) and tetrodotoxin-sensitive (TTX s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia. PMID- 27667512 TI - Epimedium koreanum Nakai and its main constituent icariin suppress lipid accumulation during adipocyte differentiation of 3T3-L1 preadipocytes. AB - Obesity is associated with a number of metabolic abnormalities such as type 2 diabetes and has become a major health problem worldwide. In the present study, we investigated the effects of Epimedium koreanum Nakai (Herba Epimedii, HE) and its main constituent icariin on the adipocyte differentiation in 3T3-L1 preadipocytes. HE extract and icariin significantly reduced lipid accumulation and suppressed the expressions of PPARgamma, C/EBPalpha, and SREBP-1c in 3T3-L1 adipocytes. They also inhibited fatty acid synthase (FAS), acyl-Co A synthase (ACS1), and perilipin. Moreover, HE extract and icariin markedly increased the phosphorylation of AMPK. These results indicated that HE extract and icariin can inhibit the adipocyte differentiation through downregulation of the adipogenic transcription factors, suggesting that HE containing icariin may be used as a potential therapeutic agent in the treatment and prevention of obesity. PMID- 27667513 TI - Identification and characterization of a novel neuropeptide (neuropeptide Y-HS) from leech salivary gland of Haemadipsa sylvestris. AB - The present study was designed to identify immunomodulatory components from the leech salivary gland of Haemadipsa sylvestris. The Sephadex G-50, Resource(TM) S column chromatography and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify the salivary gland extracts (SGE). Structural analysis of isolated compounds was based on Edman degradation and matrix assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS). The cDNA encoding the precursor of the compound was cloned from the cDNA library of the salivary gland of H. sylvestris. The levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were assayed using an enzyme-linked immunosorbent assay (ELISA). The effects on cell proliferation and cell viability were observed using MTT assay. A novel neuropeptide Y (Neuropeptide Y-HS) from the leech salivary gland of H. sylvestris was purified and characterized. It was composed of 36 amino acid residues and the amino acid sequence was determined to be FLEPPERPAVFTSVEQMKSYIKALNDYYLLLGRPRF-NH2, containing an amidated C-terminus. It showed significant inhibitory effects on the production of inflammatory cytokines including TNF-alpha, IFN-gamma, IL-6, and MCP-1. Neuropeptide Y was identified from leeches for the first time. The presence of neuropeptide Y-HS in leech salivary gland may help get blood meal from hosts and inhibit inflammation. PMID- 27667514 TI - A new biocompatible microemulsion increases extraction yield and bioavailability of Andrographis paniculata. AB - The purpose of this study was to design and prepare a biocompatible microemulsion of Andrographis paniculata (BMAP) containing both fat-soluble and water-soluble constituents. We determined the contents of active constituents of BMAP and evaluated its bioavailability. The biocompatible microemulsion (BM), containing lecithin and bile salts, was optimized in the present study, showing a good physical stability. The mean droplet size was 19.12 nm, and the average polydispersity index (PDI) was 0.153. The contents of andrographolide and dehydroandrographolide in BMAP, as determined by high performance liquid chromatography (HPLC), were higher than that in ethanol extraction. The pharmacokinetic results of BMAP showed that the AUC0-7 and AUC0->infinity values of BMAP were 2.267 and 27.156 MUg.mL(-1).h(-1), respectively, and were about 1.41 fold and 6.30-fold greater than that of ethanol extraction, respectively. These results demonstrated that the bioavailability of and rographolide extracted by BMAP was significantly higher than that extracted by ethanol. In conclusion, the BMAP preparation displayed ann improved dose form for future clinical applications. PMID- 27667515 TI - Two new limonoids isolated from the fuits of Melia toosendan. AB - In the present study, two new limonoids, 1alpha, 7alpha-dihydroxyl-3alpha acetoxyl-12alpha-ethoxylnimbolinin (1) and 1alpha-tigloyloxy-3alpha-acetoxyl 7alpha-hydroxyl-12beta-ethoxylnimbolinin (2), together with other four known limonoids (3-6), were isolated from the fruits of Melia toosendan. Their structures were elucidated by means of extensive spectroscopic analyses (NMR and ESI-MS) and comparisons with the data reported in the literature. The isolated compounds were evaluated for their antibacterial activities. Compound 4 exhibited significant antibacterial activity against an oral pathogen, Porphyromonas gingivalis ATCC 33277, with an MIC value of 15.2 MUg.mL(-1). Compound 2 was also active against P. gingivalis ATCC 33277, with an MIC value of 31.25 MUg.mL(-1). In conlcusion, our resutls indicate that these compounds may provide a basis for future development of novel antibiotics. PMID- 27667516 TI - Establishment and reliability evaluation of the design space for HPLC analysis of six alkaloids in Coptis chinensis (Huanglian) using Bayesian approach. AB - Coptis chinensis (Huanglian) is a commonly used traditional Chinese medicine (TCM) herb and alkaloids are the most important chemical constituents in it. In the present study, an isocratic reverse phase high performance liquid chromatography (RP-HPLC) method allowing the separation of six alkaloids in Huanglian was for the first time developed under the quality by design (QbD) principles. First, five chromatographic parameters were identified to construct a Plackett-Burman experimental design. The critical resolution, analysis time, and peak width were responses modeled by multivariate linear regression. The results showed that the percentage of acetonitrile, concentration of sodium dodecyl sulfate, and concentration of potassium phosphate monobasic were statistically significant parameters (P < 0.05). Then, the Box-Behnken experimental design was applied to further evaluate the interactions between the three parameters on selected responses. Full quadratic models were built and used to establish the analytical design space. Moreover, the reliability of design space was estimated by the Bayesian posterior predictive distribution. The optimal separation was predicted at 40% acetonitrile, 1.7 g.mL(-1) of sodium dodecyl sulfate and 0.03 mol.mL(-1) of potassium phosphate monobasic. Finally, the accuracy profile methodology was used to validate the established HPLC method. The results demonstrated that the QbD concept could be efficiently used to develop a robust RP-HPLC analytical method for Huanglian. PMID- 27667517 TI - Nano-LC-ESI MS/MS analysis of proteins in dried sea dragon Solenognathus hardwickii and bioinformatic analysis of its protein expression profiling. AB - The sea dragon Solenognathus hardwickii has long been used as a traditional Chinese medicine for the treatment of various diseases, such as male impotency. To gain a comprehensive insight into the protein components of the sea dragon, shotgun proteomic analysis of its protein expression profiling was conducted in the present study. Proteins were extracted from dried sea dragon using a trichloroacetic acid/acetone precipitation method and then separated by SDS-PAGE. The protein bands were cut from the gel and digested by trypsin to generate peptide mixture. The peptide fragments were then analyzed using nano liquid chromatography tandem mass spectrometry (nano-LC-ESI MS/MS). 810 proteins and 1 577 peptides were identified in the dried sea dragon. The identified proteins exhibited molecular weight values ranging from 1 900 to 3 516 900 Da and pI values from 3.8 to 12.18. Bioinformatic analysis was conducted using the DAVID Bioinformatics Resources 6.7 Gene Ontology (GO) analysis tool to explore possible functions of the identified proteins. Ascribed functions of the proteins mainly included intracellular non-membrane-bound organelle, non-membrane-bounded organelle, cytoskeleton, structural molecule activity, calcium ion binding and etc. Furthermore, possible signal networks of the identified proteins were predicted using STRING (Search Tool for the Retrieval of Interacting Genes) database. Ribosomal protein synthesis was found to play an important role in the signal network. The results of this study, to best of our knowledge, were the first to provide a reference proteome profile for the sea dragon, and would aid in the understanding of the expression and functions of the identified proteins. PMID- 27667518 TI - Pharmacokinetic profiles of falcarindiol and oplopandiol in rats after oral administration of polyynes extract of Oplopanax elatus. AB - Polyynes, such as facarindiol (FAD) and oplopandiol (OPD), are responsible for anticancer activities of Oplopanax elatus (O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry (LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane (V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column (4.6 mm * 50 mm, 1.8 MUm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 mL.min(-1) within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring (SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus. PMID- 27667519 TI - A Highly Sensitive Assay Using Synthetic Blood Containing Test Microbes for Evaluation of the Penetration Resistance of Protective Clothing Material under Applied Pressure. AB - To prevent nosocomial infections caused by even either Ebola virus or methicillin resistant Staphylococcus aureus (MRSA), healthcare workers must wear the appropriate protective clothing which can inhibit contact transmission of these pathogens. Therefore, it is necessary to evaluate the performance of protective clothing for penetration resistance against infectious agents. In Japan, some standard methods were established to evaluate the penetration resistance of protective clothing fabric materials under applied pressure. However, these methods only roughly classified the penetration resistance of fabrics, and the detection sensitivity of the methods and the penetration amount with respect to the relationship between blood and the pathogen have not been studied in detail. Moreover, no standard method using bacteria for evaluation is known. Here, to evaluate penetration resistance of protective clothing materials under applied pressure, the detection sensitivity and the leak amount were investigated by using synthetic blood containing bacteriophage phi-X174 or S. aureus. And the volume of leaked synthetic blood and the amount of test microbe penetration were simultaneously quantified. Our results showed that the penetration detection sensitivity achieved using a test microbial culture was higher than that achieved using synthetic blood at invisible leak level pressures. This finding suggested that there is a potential risk of pathogen penetration even when visual leak of contaminated blood through the protective clothing was not observed. Moreover, at visible leak level pressures, it was found that the amount of test microbe penetration varied at least ten-fold among protective clothing materials classified into the same class of penetration resistance. Analysis of the penetration amount revealed a significant correlation between the volume of penetrated synthetic blood and the amount of test microbe penetration, indicating that the leaked volume of synthetic blood could be considered as a latent indicator for infection risk, that the amount of exposure to contaminated blood corresponds to the risk of infection. Our study helped us ascertain, with high sensitivity, the differences among fabric materials with respect to their protective performance, which may facilitate effective selection of protective clothing depending on the risk assessment. PMID- 27667520 TI - Antifreeze Activity of Xylomannan from the Mycelium and Fruit Body of Flammulina velutipes. AB - An identified class of antifreeze, a xylomannan-based thermal hysteresis (TH) producing glycolipid, has been discovered from diverse taxa, including plants, insects, and amphibians. We isolated xylomannan from the mycelium and fruit body of the basidiomycete Flammulina velutipes using successive hot extraction with water, 2% and 25% aqueous KOH, and gel filtration chromatography. The xylomannan from the fruit body had a recrystallization inhibiting (RI) activity (RI=0.44) at 0.5 mg/mL. The dried weight yield of the fruit body (7.7*10(-2)%, w/w) was higher than that of the mycelium. Although the purified xylomannan from both soures were composed of mannose and xylose in a 2 : 1 molar ratio, the molecular weight of the xylomannan from the mycelium and fruit body was 320,000 and 240,000, respectively. The RI activity of mycelial xylomannan was higher than that from the fruit body (RI=0.57) at 45 ug/mL. Although this RI activity was able to remain constant after exposure to various conditions, we confirmed that the decrease of RI activity was stimulated by the decrease of molecular weight that was caused by heating during the alkaline condition. The survival rate of the CHO cells at -20C for two days increased to 97% due to the addition of 20 ug/mL of purified xylomannan. This was the first report to indicate that xylomannan from the mycelium of Flammulina velutipes had a high level of ice recrystallization inhibiting activity like antifreeze proteins from plants and had rhe potential to become a new material for cell storage. PMID- 27667521 TI - Development of a DNA Array for the Simple Identification of Major Filamentous Fungi in the Beverage Manufacturing Environment. AB - Filamentous fungi were isolated from the indoor environment of a soft drink manufacturing plant and ordinary residences. The isolated strains were identified based on morphological observation and the nucleotide sequences of the region near the D2 region of the 26S rDNA. Three genera (Aspergillus, Penicillium, and Cladosporium) accounted for 48.1% of the fungal strains detected in the manufacturing plant and 75.3% in residences. A DNA array for identification of 15 genera and 26 species of filamentous fungi that were most frequently isolated from the manufacturing plant was developed. Genus- and species-specific probes with 13- to 20-mer were designed on the basis of the nucleotide sequences in the D2 region. The probes were affixed to a microscope slide after modifying an amino group at the 5'or 3'end. To prevent erroneous identification, 2 or 3 probes were designed for each of the target genera and species. The developed DNA array method correctly identified 9 genera (Alternaria, Aureobasidium, Cladosporium, Curvularia, Exophiala, Fusarium, Penicillium, Phoma, and Trichoderma) and 26 species belonging to 6 genera (Aspergillus, Neosartorya, Byssochlamys, Talaromyces, Paecilomyces, and Purpureocillium) in the strains isolated from the indoor environment. Identification results obtained by this DNA array method of fungi isolated from the manufacturing plant were consistent with those by the conventional method. PMID- 27667522 TI - Synergistic Effect of Photosynthetic Bacteria and Isolated Bacteria in Their Antifungal Activities against Root Rot Fungi. AB - Antifungal bacteria (AB) in root rot fungus (RRF)-contaminated sweet potato farms were isolated, and seven strains were initially chosen as antagonistic candidates. An antagonistic test by using the mycelial disk placement method revealed that one AB strain by itself could inhibit the RRF growth. This AB strain was identified as Bacillus polyfermenticus based on phylogeny of 16S ribosomal RNA genes. Two AB strains (Bacillus aerophilus) displayed high levels of antifungal activity when paired with photosynthetic bacterial strain A (a purple nonsulfur photosynthetic bacterium Rhodopseudomonas faecalis). The results suggest the possible use of the isolates as agents for the biological control of the RRF infection of agricultural products in fields of cultivation. PMID- 27667523 TI - Roles of Catalase and Trehalose in the Protection from Hydrogen Peroxide Toxicity in Saccharomyces cerevisiae. AB - The roles of catalase and trehalose in Saccharomyces cerevisiae subject to hydrogen peroxide (H2O2) treatment were examined by measuring the catalase activity and intracellular trehalose levels in mutants lacking catalase or trehalose synthetase. Intracellular trehalose was elevated but the survival rate after H2O2 treatment remained low in mutants with deletion of the Catalase T gene. On the other hand, deletion of the trehalose synthetase gene increased the catalase activity in mutated yeast to levels higher than those in the wild-type strain, and these mutants exhibited some degree of tolerance to H2O2 treatment. These results suggest that Catalase T is critical in the yeast response to oxidative damage caused by H2O2 treatment, but trehalose also plays a role in protection against H2O2 treatment. PMID- 27667524 TI - Similarity in the Structure of tetD-Carrying Mobile Genetic Elements in Bacterial Strains of Different Genera Isolated from Cultured Yellowtail. AB - Structure analysis was performed on the antibiotic-resistance-gene region of conjugative plasmids of four fish farm bacteria.The kanamycin resistance gene, IS26, and tetracycline resistance gene (tetA(D)) were flanked by two IS26s in opposite orientation in Citrobacter sp. TA3 and TA6, and Alteromonas sp. TA55 from fish farm A. IS26-Inner was disrupted with ISRSB101. The chloramphenicol resistance gene, IS26 and tetA (D) were flanked by two IS26s in direct orientation in Salmonella sp. TC67 from farm C. Structures of tetA (D) and IS26 were identical among the four bacteria, but there was no insertion within the IS26-Inner of Salmonella sp. TC67. Horizontal gene transfer between the strains of two different genera in fish farm A was suggested by the structure homologies of mobile genetic elements and antibiotic resistance genes. PMID- 27667525 TI - Bactericidal Action of Photodynamic Antimicrobial Chemotherapy (PACT) with Photosensitizers Used as Plaque-Disclosing Agents against Experimental Biofilm. AB - Our previous study revealed that the photo-irradiation of rose bengal, erythrosine, and phloxine, xanthene photosensitizers, used as dental plaque disclosing agents, could exert bactericidal action on planktonic Streptococcus mutans via the singlet oxygen. In the present study, the photo-irradiation induced bactericidal activity of the three xanthene compounds against the experimental biofilm of S. mutans was investigated in combination with acid electrolyzed water (AcEW) and alkaline electrolyzed water (AlEW). As a result, only the photo-irradiated rose bengal in AlEW showed prominent bactericidal activity with a >3-log reduction of the viable bacterial count. Since our previous study showed that the affinity of rose bengal to bacterial cells was superior to that of erythrosine and phloxine, it was speculated that AlEW damaged the extracellular matrix of the experimental biofilm, which would let the rose bengal easily be bound to the bacterial cells. From these results, it is strongly suggested that rose bengal is a suitable photosensitizer for use as a plaque disclosing agent in photodynamic antimicrobial chemotherapy to treat dental plaque. PMID- 27667526 TI - Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma. AB - We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification. PMID- 27667527 TI - Conservative management of mandibular dentinogenic ghost cell tumours: a minimally invasive approach. PMID- 27667528 TI - Reanimation surgery in patients with acquired bilateral facial palsy. AB - Acquired bilateral facial palsy is rare and causes difficulty with speech and eating, but dynamic reanimation of the face can reduce the effect of these problems. Of 712 patients who had these procedures during our study period, two had an acquired bilateral facial paralysis. In both, reanimation was completed in a single operation using a free-functional transfer of the latissimus dorsi muscle that was coapted to the masseteric branch of the trigeminal nerve. Both patients achieved excellent non-spontaneous excursion and an improvement in function. Careful evaluation of the available donor nerves including thorough examination and electromyographic testing should always be completed before operation. PMID- 27667529 TI - Relationship between skeletal muscle mass and hepatic fibrosis in patients with type 2 diabetes. PMID- 27667530 TI - 5'-N-ethylcarboxamidoadenosine is not a paralog-specific Hsp90 inhibitor. AB - The molecular chaperone Hsp90 facilitates the folding and modulates activation of diverse substrate proteins. Unlike other heat shock proteins such as Hsp60 and Hsp70, Hsp90 plays critical regulatory roles by maintaining active states of kinases, many of which are overactive in cancer cells. Four Hsp90 paralogs are expressed in eukaryotic cells: Hsp90alpha/beta (in the cytosol), Grp94 (in the endoplasmic reticulum), Trap1 (in mitochondria). Although numerous Hsp90 inhibitors are being tested in cancer clinical trials, little is known about why different Hsp90 inhibitors show specificity among Hsp90 paralogs. The paralog specificity of Hsp90 inhibitors is likely fundamental to inhibitor efficacy and side effects. In hopes of gaining insight into this issue we examined NECA (5'-N ethylcarboxamidoadenosine), which has been claimed to be an example of a highly specific ligand that binds to one paralog, Grp94, but not cytosolic Hsp90. To our surprise we find that NECA inhibits many different Hsp90 proteins (Grp94, Hsp90alpha, Trap1, yeast Hsp82, bacterial HtpG). NMR experiments demonstrate that NECA can bind to the N-terminal domains of Grp94 and Hsp82. We use ATPase competition experiments to quantify the inhibitory power of NECA for different Hsp90 proteins. This scale: Hsp82 > Hsp90alpha > HtpG ~ Grp94 > Trap1, ranks Grp94 as less sensitive to NECA inhibition. Because NECA is primarily used as an adenosine receptor agonist, our results also suggest that cell biological experiments utilizing NECA may have confounding effects from cytosolic Hsp90 inhibition. PMID- 27667531 TI - Are Midterm Patient-Reported Outcome Measures Between Rotating-Platform Mobile Bearing Prosthesis and Medial-Pivot Prosthesis Different? A Minimum of 5-Year Follow-Up Study. AB - BACKGROUND: Both rotating-platform (RP) mobile-bearing and medial-pivot (MP) fixed-bearing prostheses allow axial femorotibial rotation using a highly conforming polyethylene insert. However, limited comparative data are available between the 2 designs. This study was performed to compare the midterm clinical outcomes and patient-reported outcome measures (PROMs) of RP and MP prostheses. METHODS: We retrospectively reviewed the records of 52 total knee arthroplasties using RP mobile-bearing prosthesis and 49 total knee arthroplasties using MP fixed prosthesis with a minimum follow-up period of 5 years. Clinical and radiological outcomes, failure rates, and PROMs, including the Western Ontario and McMaster Universities Osteoarthritis Index score and satisfaction, were compared. RESULTS: There was no difference in clinical or radiographic outcomes (P > .1 for all comparisons), with the exception of the larger flexion contracture (FC) in the MP group (0.3 degrees in RP vs 2.3 degrees in MP, P < .01). No failure in either group was recorded during the study period. PROMs were comparable (P > .1 in all comparisons), with the exception of higher satisfactions in the RP group while performing light household duties (P < .01) and leisure or recreational activities (P = .014) in patients without FC. CONCLUSION: The midterm clinical results with both the RP mobile-bearing and MP fixed-bearing prostheses were satisfactory. Although both prostheses provided comparable PROMs, patients with an RP prosthesis were more satisfied than those with an MP prosthesis for highly demanding activities that are strongly associated with the presence of postoperative FC. PMID- 27667532 TI - Intraoperative Fluoroscopic Assessment of Limb Alignment is a Reliable Predictor for Postoperative Limb Alignment in Biplanar Medial Opening-Wedge High Tibial Osteotomy. AB - BACKGROUND: The purpose of this study was to assess the reliability of pre-, intra operative, and postoperative limb alignment measurements and investigate the correlation between the measurements in biplanar medial opening-wedge high tibial osteotomy. METHODS: This study enrolled 59 knees undergoing biplanar opening-wedge high tibial osteotomy for primary medial osteoarthritis with varus deformity. Preoperative and postoperative standing lower leg radiographs and intraoperative fluoroscopic images were taken. Two independent examiners analyzed the radiologic data to assess lower limb alignment and mechanical axis (MA) deviation (percentage of MA position on tibial plateau). The effect of preoperative hip-knee-ankle angle and MA deviation, age, sex, body mass index (BMI), and joint line convergence angle on the discrepancy between intraoperative and postoperative MA deviation was analyzed. RESULTS: The mean preoperative hip knee-ankle angle and MA deviation were varus 7.7 +/- 3.3 degrees and 14.1 +/- 15.1%, respectively. After osteotomy, the mean intraoperative postosteotomy MA deviation was 57.9 +/- 2.1% in supine position, and the mean post-operative MA deviation increased to 63.9 +/- 2.9% on standing radiographs. The mean difference between intraoperative postosteotomy MA deviation and postoperative MA deviation was 6.1 +/- 2.2%. Linear regression analysis between intraoperative postosteotomy MA deviation and postoperative MA deviation showed a statistically significant linear relationship (R2 = 0.449; P < .001). Multivariate regression analysis revealed that preoperative joint line convergence angle (beta = 0.856; P < .001) and BMI (beta = 0.349; P < .001) were significant positive predictors for the difference in MA deviation. CONCLUSION: There was a significant linear relationship between intraoperative postosteotomy MA deviation and postoperative MA deviation following biplanar medial opening-wedge high tibial osteotomy. A greater discrepancy between MA deviations was significantly associated with higher BMI and joint line convergence angle. PMID- 27667533 TI - Periarticular Injection of Liposomal Bupivacaine Offers No Benefit Over Standard Bupivacaine in Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial. AB - BACKGROUND: Periarticular injection of liposomal bupivacaine has been adopted as part of multimodal pain management after total knee arthroplasty (TKA). METHODS: In this prospective, randomized clinical trial, we enrolled 162 patients undergoing primary TKA in a single institution between January 2014 and May 2015. Eighty-seven patients were randomized to liposomal bupivacaine (experimental group), and 75 patients were randomized to free bupivacaine (control group). All patients received spinal anesthesia and otherwise identical surgical approaches, pain management, and rehabilitation protocols. Outcomes evaluated include the patient-reported visual analog pain scores, narcotic consumption, and narcotic related side effects (Brief Pain Inventory) within 96 hours after surgery as well as functional outcomes using the Knee Society Score and the Short-Form 12 measured preoperatively and at 4-6 weeks after surgery. RESULTS: There were no statistically significant differences between the groups in terms of postoperative daily pain scores, narcotic consumption (by-day and overall), or narcotic-related side effects. There were no statistically significant differences between the groups in terms of surgical (P = .76) and medical complications or length of hospital stay (P = .35). There were no statistically significant differences in satisfaction between the groups (P = .56) or between the groups in postoperative Knee Society Score (P = .53) and the Short-Form 12 at 4-6 weeks (P = .82, P = .66). CONCLUSION: As part of multimodal pain management protocol, periarticular injection of liposomal bupivacaine compared with bupivacaine HCl did not result in any clinically or statistically significant improvement of the measured outcomes following TKA. PMID- 27667534 TI - Accelerometer-Based, Portable Navigation (KneeAlign) vs Conventional Instrumentation for Total Knee Arthroplasty: A Prospective Randomized Comparative Trial. AB - BACKGROUND: Accelerometer-based, portable navigation devices have been introduced as a less invasive and simpler technique to perform navigated surgical implantation of knee prostheses. They have been postulated to have better accuracy than conventional instruments in restoration of alignment in total knee arthroplasty. METHODS: A total of 190 patients were enrolled in this prospective, randomized controlled trial and underwent total knee arthroplasty using either the KneeAlign or conventional guides. Multiplanar alignment was evaluated with a CT imaging protocol. RESULTS: A total of 86.5% of portable navigation device and 82.2% of conventional group had a postoperative hip-knee angle within 3 degrees of neutral alignment (P = .54). There was no significant difference between the 2 groups for component coronal and sagittal plane alignment. Portable navigation device did not significantly increase the time to perform the surgery. CONCLUSION: Portable navigation device demonstrates accurate restoration of alignment; however, there was no statistically significant difference when compared with conventional guides. PMID- 27667536 TI - Surgical Innovation and the Multiple Meanings of Randomized Controlled Trials: The First RCT on Minimally Invasive Cholecystectomy (1980-2000). AB - This article uses the case of the first randomized controlled trial (RCT) evaluating laparoscopic cholecystectomy to investigate the introduction of minimally invasive surgery in the 1990s and explore the meaning of RCTs within the context of the introduction of a new surgical technology. It thus brings together the history of the use of laparoscopic cholecystectomy to remove the gallbladder, and the history of the RCT, shedding light on particular aspects of both. We first situate the RCT in the context of the history of the various treatment options for gallstones, or cholelithiasis, then characterize the specific situation of the rapid, patient-driven spread of laparoscopic cholecystectomy, and in a next step describe how the local context of laparoscopic cholecystectomy as a new technology made it possible and desirable to conduct an RCT, despite numerous obstacles. This article then shows that in order to capture and understand the rationale of an RCT it is worth it to explore the various levels and dimensions of its context, demonstrating how even the RCT as an ostensibly universal tool draws its meaning from its contexts and that this meaning goes beyond the simple determination of efficiency and safety, including, maybe most importantly, the control and management of new technologies. PMID- 27667535 TI - Total Hip Arthroplasty After Periacetabular and Intertrochanteric Valgus Osteotomy. AB - BACKGROUND: We performed periacetabular osteotomy (PAO) combined with intertrochanteric valgus osteotomy (TVO) to obtain better congruity for patients with acetabular dysplasia and nonspherical femoral head. These patients with PAO combined TVO demonstrate long-term progression of osteoarthritis, thereby, needing conversion to total hip arthroplasty (THA) and is difficult due to morphological changes. The objective of the present study was to investigate outcomes of patients who underwent THA after PAO-combined TVO. METHODS: We performed 3 groups' case-control study. The participants were 20 patients (20 hips) who underwent THA after PAO-combined TVO (PAO-TVO group); these patients had a mean age at surgery of 56.3 years and underwent postoperative follow-up for a mean period of 6.8 years. For the control group, we included 53 patients (57 joints) who underwent THA after PAO and 76 patients (80 joints) who underwent primary THA for hip dysplasia matching age, sex, and time of surgery. RESULTS: Harris hip score at the last follow-up was significantly poorer in PAO-TVO group compare with PAO group and primary group. Short Form-36 of Physical Component Summary was significantly poorer in PAO-TVO group compared with primary group. The socket position in the PAO-TVO group was significantly superior and lateral compared with that in the primary THA group. Considering socket placement in Lewinnek's safe zone and stem malalignment, there were no significant differences in the 3 groups. CONCLUSION: Harris hip score and Short Form-36-Physical Component Summary for THA after PAO-combined TVO were significantly poorer compared to those of primary THA. PMID- 27667537 TI - Shrinking the Psoriasis Assessment Gap: Early Gene-Expression Profiling Accurately Predicts Response to Long-Term Treatment. AB - There is an "assessment gap" between the moment a patient's response to treatment is biologically determined and when a response can actually be determined clinically. Patients' biochemical profiles are a major determinant of clinical outcome for a given treatment. It is therefore feasible that molecular-level patient information could be used to decrease the assessment gap. Thanks to clinically accessible biopsy samples, high-quality molecular data for psoriasis patients are widely available. Psoriasis is therefore an excellent disease for testing the prospect of predicting treatment outcome from molecular data. Our study shows that gene-expression profiles of psoriasis skin lesions, taken in the first 4 weeks of treatment, can be used to accurately predict (>80% area under the receiver operating characteristic curve) the clinical endpoint at 12 weeks. This could decrease the psoriasis assessment gap by 2 months. We present two distinct prediction modes: a universal predictor, aimed at forecasting the efficacy of untested drugs, and specific predictors aimed at forecasting clinical response to treatment with four specific drugs: etanercept, ustekinumab, adalimumab, and methotrexate. We also develop two forms of prediction: one from detailed, platform-specific data and one from platform-independent, pathway-based data. We show that key biomarkers are associated with responses to drugs and doses and thus provide insight into the biology of pathogenesis reversion. PMID- 27667538 TI - Synthesis, characterization and antioxidant activity of selenium polysaccharide from Cordyceps militaris. AB - A purified selenium-containing derivatives of Cordyceps militaris polysaccharide synthesized using H2SeO3/HNO3 and BaCl2 as a catalyst was investigated in this paper. The reaction condition was optimized by selecting different reaction temperature and period. Afterward, the one with the highest Se content was purified by ultra-filtration device with a molecular cut off size of 10KDa. Followed by its structural characterizations. Results of IFR and 13C NMR spectroscopy indicated that C-6 substitution was predominant in selenized polysaccharide. The modified polysaccharide with molecular weight of 1998 KDa was mainly consisted of mannose, glucose and galactose in the mole ratios of with the mole ratios of 1:28.63:1.41. Thermogravimetric and morphological analyses of the samples were carried out by AFS, SEM and AFM. In addition, the in vitro antioxidant results suggested that selenium-containing polysaccharide should be applied as a novel selenium source in dietary supplements, with potent antioxidant properties. PMID- 27667539 TI - Structural and thermal characterization of PHAs produced by Lysinibacillus sp. through submerged fermentation process. AB - In this investigation an attempt has been made to characterize and identify Lysinibacillus sp. 3HHX by 16S-rDNA sequencing. The bacterium exhibited occurrence of PHAs granules on an average 11+/-1 per cell of 1.0MUm length and breadth 0.72MUm, revealed from TEM studies. Under optimized condition, 4.006gm/L of PHAs was extracted using hypochlorite digestion and multi-solvent extraction process. PhaC gene of ~540bp and higher PHA synthase activity was detected at 48h of cultivation. The extracted PHAs was structurally characterized by GC-MS and 1H NMR reported to be P(3HB-co-3HDD-co-3HTD) and amorphous in nature with 112 degrees C melting point, -11.0 degrees C glass transition point and 114.76 degrees C decomposition temperature detected by DSC & TGA respectively. The C/O of biopolymer disc was 1:65 as revealed from C1s and O1s spectra of XPS, that was completely biodegradable within 30 days. This biopolymer was observed to be non cytotoxic to NIH 3T3 mouse fibroblast cells. The report is of its kind in establishing the abilities of Lysinibacillus sp. 3HHX for non-growth associated PHA co-polymer production. Moreover the biocompatible and biodegradable nature of the biopolymer conferred to its substantial biomedical applications. PMID- 27667540 TI - The preparation and study of cellulose carbamates and their regenerated membranes. AB - Using wood pulps with the average degree of polymerization 300-350 and urea as raw materials, cellulose carbamates were successfully synthesized by esterification reaction in N, N-dimethylacetamide(DMAc), an inexpensive, high boiling aprotic and polar solvent, for the purpose of improving the solubility of cellulose, reducing costs and environmental pollution. The products were dissolved in 9% sodium hydroxide solution at a low temperature after washing and drying and the cellulose carbamates solutions were obtained. The solutions were uniformly casted on a glass support after degassing. The regenerated cellulose membranes (CMs) were prepared by immersing the support in coagulation bath for some minutes. The structures of cellulose carbamates were characterized by Fourier transform infrared spectroscopy (FT-IR), 13C solid state nuclear magnetic resonance spectrometry (13C NMR), Thermal gravimetric analysis(TG), Scanning electron microscopy (SEM) and X-ray diffractometry(XRD). The filtration performances of CMs were tested. The results reveal that part groups of cellulose were substituted by amino in the medium, the cellulose carbamates were prepared with the reducing crystallinity and thermal decomposition temperature. The CMs have good separation performance for methylene blue. PMID- 27667541 TI - Production and characterization of polycaprolactone- hyaluronic acid/chitosan- zein electrospun bilayer nanofibrous membrane for tissue regeneration. AB - A bilayered electrospun membrane was produced in this study, using the electrospinning technique, to be applied as a skin substitute. The upper layer of the membrane was comprised by hyaluronic acid and polycaprolactone in order to provide mechanical support and also to act as a physical barrier against external threats. Chitosan and zein were used to produce the bottom layer that was loaded with salicylic acid, in order to confer anti-inflammatory and antimicrobial activity to this layer. The physicochemical properties of the membranes were determined and the obtained results showed that the produced electrospun membrane display an ideal porosity, appropriate mechanical properties, controlled water loss and a suitable salicylic acid release profile. In addition, membranes did not exhibit any toxic effects for human fibroblast cells, since cells were able to adhere, spread and proliferate. Furthermore, no biofilm formation was noticed on membranes' surface along the experiments. In conclusion, the gathered data reveal that this electrospun membrane has suitable properties to be used as a wound dressing. PMID- 27667542 TI - Sickle cell disease: Its molecular mechanism and the one drug that treats it. AB - Sickle cell disease is probably the first known assembly disease, and its mechanism has been extensively studied. It arises because of the expression of a mutant hemoglobin that can polymerize, and which does so by a double nucleation mechanism that is now seen to operate in other diseases. The polymers so formed lead to circulatory obstruction in the microcirculation. The accuracy of the description that has been developed is sufficient to describe precisely the impact of molecules that cannot join polymers but that still crowd the solution, including fetal hemoglobin. The one approved drug, hydroxyurea, is thought to achieve its benefit by enhancing the production of fetal hemoglobin, but the effects of the drug on polymerization exceed what the added fetal hemoglobin can accomplish. While some possible answers to this mystery are suggested, no mechanism has been conclusively established for the remarkably efficacy of the one drug available to treat this disease. PMID- 27667543 TI - Alginate-based microcapsules with galactosylated chitosan internal for primary hepatocyte applications. AB - Alginate-galactosylated chitosan/polylysine (AGCP) microcapsules with excellent stability and high permeability were developed and employed in primary hepatocyte applications. The galactosylated chitosan (GC), synthesized via the covalent coupling of lactobionic acid (LA) with low molecular weight and water-soluble chitosan (CS), was ingeniously introduced into the core of alginate microcapsules by regulating the pH of gelling bath. The internal GC of the microcapsules simultaneously provided a large number of binding sites for the hepatocytes and further promoted the hepatocyte-matrix interactions via the recognition of asialoglycoprotein receptors (ASGPRs) on the hepatocyte surface, and afforded the AGCP microcapsules an excellent stability via the electrostatic interactions with alginate. As a consequence, primary hepatocytes in AGCP microcapsules demonstrated enhanced viability, urea synthesis, albumin secretion, and P-450 enzyme activity, showing great prospects for hepatocyte applications in microcapsule system. PMID- 27667544 TI - The chitin-binding domain of a GH-18 chitinase from Vibrio harveyi is crucial for chitin-chitinase interactions. AB - Vibrio harveyi chitinase A (VhChiA) is a GH-18 glycosyl hydrolase with a structure containing three distinct domains: i) the N-terminal chitin-binding domain; ii) the (alpha/beta)8 TIM barrel catalytic domain; and iii) the alpha+beta insertion domain. In this study, we cloned the gene fragment encoding the chitin-binding domain of VhChiA, termed ChBDVhChiA. The recombinant ChBDVhChiA was heterologously expressed in E. coli BL21 strain Tuner(DE3)pLacI host cells, and purified to homogeneity. CD measurements suggested that ChBDVhChiA contained beta-sheets as major structural components and fluorescence spectroscopy showed that the protein domain was folded correctly, and suitable for functional characterization. Chitin binding assays showed that ChBDVhChiA bound to both alpha- and beta-chitins, with the greatest affinity for beta colloidal chitin, but barely bound to polymeric chitosan. These results identified the tandem N-acetamido functionality on chitin chains as the specific sites of enzyme-substrate interactions. The binding affinity of the isolated domain was significantly lower than that of intact VhChiA, suggesting that the catalytic domain works synergistically with the chitin-binding domain to guide the polymeric substrate into the substrate binding cleft. These data confirm the physiological role of the chitin-binding domain of the marine bacterial GH-18 chitinase A in chitin-chitinase interactions. PMID- 27667545 TI - Erratum to "Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998-2013)". PMID- 27667546 TI - Long-term outcomes of simplified gingivoperiosteoplasty performed at the time of hard palatal closure: A review of 55 alveolar clefts. AB - Few studies have examined the long-term outcomes of gingivoperiosteoplasty at the age of permanent canine eruption. The success rates of gingivoperiosteoplasty vary significantly depending on the surgeon because of the difficulty of the surgical technique. Therefore, the authors utilized a simplified gingivoperiosteoplasty technique by inserting one or two large, triangular-shaped mucoperiosteal flaps on the opposite side in a tongue-in-groove or interdigitation fashion. The purpose of this study was to evaluate the long-term outcomes of this simplified gingivoperiosteoplasty technique at the age of permanent canine eruption. Forty nonsyndromic cleft lip and palate patients who had undergone simplified gingivoperiosteoplasty were retrospectively reviewed. Canine eruption and the bone formation rate of the interalveolar septum using the Bergland method and a modified Long et al. method were evaluated. A total of 55 alveolar cleft sites were treated. Simplified gingivoperiosteoplasty was performed at a mean age of 13.4 months, and the mean age at the time of follow-up was 14.3 years. The overall success rate of simplified gingivoperiosteoplasty was 50.90%. With regard to cleft types, clefts of the primary palate and unilateral alveolar clefts showed a significantly higher success rate than clefts of the primary and secondary palates and bilateral alveolar clefts, respectively. Our gingivoperiosteoplasty technique is a simple surgical procedure and is performed at 12 months of age, at which time the cleft alveolus has grown sufficiently, to ensure the success of the delicate surgical technique. Therefore, we could obtain favorable outcomes. PMID- 27667547 TI - Arteriovenous loop graft in abdominal wall reconstruction using free tissue transfer. PMID- 27667548 TI - Baicalein inhibits TNF-alpha-induced NF-kappaB activation and expression of NF kappaB-regulated target gene products. AB - The nuclear factor-kappaB (NF-kappaB) transcription factors control many physiological processes including inflammation, immunity, apoptosis and angiogenesis. In our search for NF-kappaB inhibitors from natural resources, we identified baicalein from Scutellaria baicalensis as an inhibitor of NF-kappaB activation. As examined by the NF-kappaB luciferase reporter assay, we found that baicalein suppressed TNF-alpha-induced NF-kappaB activation in a dose-dependent manner. It also inhibited TNF-alpha-induced nuclear translocation of p65 through inhibition of phosphorylation and degradation of IkappaBalpha. Furthermore, baicalein blocked the TNF-alpha-induced expression of NF-kappaB target genes involved in anti-apoptosis (cIAP-1, cIAP-2, FLIP and BCL-2), proliferation (COX 2, cyclin D1 and c-Myc), invasion (MMP-9), angiogenesis (VEGF) and major inflammatory cytokines (IL-8 and MCP1). The flow cytometric analysis indicated that baicalein potentiated TNF-alpha-induced apoptosis and induced G1 phase arrest in HeLa cells. Moreover, baicalein significantly blocked activation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2). Our results imply that baicalein could be a lead compound for the modulation of inflammatory diseases as well as certain cancers in which inhibition of NF-kappaB activity may be desirable. PMID- 27667550 TI - Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin 4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis. AB - Thirty three derivatives of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3 d]pyrimidin-4-amine analogues were synthesized by molecular modification of a reported antimycobacterial molecule (GSK163574A). Compounds were evaluated in vitro against actively replicative and nutrient starved non-replicative Mycobacterium tuberculosis (MTB), enzymatic screening and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-ethyl-N-phenethyl-5,6,7,8 tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine (5c) was found to be the most active compound against non-replicative MTB with 2.7 log reduction of bacteria at 10MUg/mL and was more potent than isoniazid (1.2 log reduction) and rifampicin (2.0 log reduction) at same dose level. Compound 5c also showed activity against MTB alanine dehydrogenase enzyme with IC50 of 1.82+/-0.42MUM and showed 25% cytotoxicity against RAW 264.7 cell line at 50MUg/mL. PMID- 27667549 TI - Prevalence and predictors of delayed gastric emptying among Indian patients with long-standing type 2 diabetes mellitus. AB - BACKGROUND AND AIMS: Upper gastrointestinal symptoms are more prevalent among type 2 diabetes mellitus (T2DM) patients. The prevalence of delayed gastric emptying (GE) and factors predictive of it have not been studied in Indian T2DM patients and the present study aimed to study the same. METHODS: This hospital based cross-sectional study involved adult (age between 18 and 65 years) outpatients with T2DM of >=5-year duration. Measurements of GE of a labelled standardized solid rice idli meal by gastric emptying scintigraphy (GES), symptoms of delayed GE (by standardized questionnaire) and autonomic function by cardiovascular autonomic function tests (AFTs) were carried out. Thirty healthy subjects served as controls for GES and AFTs. RESULTS: One hundred and forty T2DM patients (age range: 32-65 years) were studied. Delayed GE was documented in ~29 % (40/140) and rapid GE in 2 % (3/140) of T2DM patients. Univariate analysis showed significant positive association between delayed GE and duration of DM, body mass index (BMI), HbA1c, retinopathy, peripheral neuropathy, autonomic dysfunction and coronary artery disease (p < 0.05 for all). However, there was no significant correlation of age, sex, symptoms suggestive of gastroparesis and nephropathy with delayed GE. Hypoglycemic episodes were significantly more frequent in those with delayed GE (p < 0.05). Multiple logistic regression analysis revealed only BMI and HbA1c to be significant independent predictors of delayed GE. CONCLUSION: Presence and severity of symptoms of gastroparesis did not predict delayed GE. Delayed GE, irrespective of symptoms, was associated with microvascular and macrovascular diabetic complications and increased risk of hypoglycemic episodes. HbA1c and BMI were independent predictors of delayed GE. PMID- 27667551 TI - An efficient protocol for obtaining accurate hydration free energies using quantum chemistry and reweighting from molecular dynamics simulations. AB - The non-Boltzmann Bennett (NBB) free energy estimator method is applied to 21 molecules from the blind subset of the SAMPL4 challenge. When NBB is applied with the SMD implicit solvent model, and the OLYP/DZP level of quantum chemistry, highly accurate hydration free energy calculations are obtained with respect to experiment (RMSD=0.89kcal.mol-1). Other quantum chemical methods are also tested, and the effects of solvent model, density functional, basis set are explored in this benchmarking study, providing a framework for improvements in calculating hydration free energies. We provide a practical guide for using the best QM-NBB protocols that are consistently more accurate than either pure QM or pure MM alone. In situations where high accuracy hydration free energy predictions are needed, the QM-NBB method with SMD implicit solvent should be the first choice of quantum chemists. PMID- 27667552 TI - Conjugation of N-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents. AB - Malaria, caused by several Plasmodium species, is the major life-threatening parasitic infection worldwide. Due to the parasite resistance to quinoline based drugs, the search for antimalarial agents is necessary. Here, we report the structural design, synthesis and antiparasitic evaluation of two novel series of 1,2,4-oxadiazoles in conjugation to N-acylhydrazones, both groups recognized as privileged structures, as well as the studies on the antimalarial activity of 16 previous described analogues. By varying substituents attached to the phenyl ring, it was possible to retain, enhance or increase the antiparasitic activity in comparison to the nonsubstituted derivatives. Replacement of substituted aryl rings by ferrocenyl and cinnamyl moieties attached in the N-acylhydrazone ablated the antiparasitic response, evidencing the structural features associated with the activity. Active compounds exhibited in vitro potency similar to mefloquine, but not all inhibited beta-hematin formation. Additionally, the active compounds displayed low cytotoxicity in HepG2 cells and did not cause hemolysis in uninfected erythrocytes. In Plasmodium berghei-infected mice, the compounds reduced parasitemia but exhibited limited efficacy in increasing mice survival when compared to chloroquine, suggesting that pharmacological improvement is still necessary. PMID- 27667554 TI - Personality-dependent differences in problem-solving performance in a social context reflect foraging strategies. AB - Individuals develop innovative behaviours to solve foraging challenges in the face of changing environmental conditions. Little is known about how individuals differ in their tendency to solve problems and in their subsequent use of this solving behaviour in social contexts. Here we investigated whether individual variation in problem-solving performance could be explained by differences in the likelihood of solving the task, or if they reflect differences in foraging strategy. We tested this by studying the use of a novel foraging skill in groups of great tits (Parus major), consisting of three naive individuals with different personality, and one knowledgeable tutor. We presented them with multiple, identical foraging devices over eight trials. Though birds of different personality type did not differ in solving latency; fast and slow explorers showed a steeper increase over time in their solving rate, compared to intermediate explorers. Despite equal solving potential, personality influenced the subsequent use of the skill, as well as the pay-off received from solving. Thus, variation in the tendency to solve the task reflected differences in foraging strategy among individuals linked to their personality. These results emphasize the importance of considering the social context to fully understand the implications of learning novel skills. PMID- 27667553 TI - Design, synthesis and biological evaluation of lapachol derivatives possessing indole scaffolds as topoisomerase I inhibitors. AB - A series of novel lapachol derivatives possessing indole scaffolds was designed and synthesized. The in vitro anti-proliferative activity of these novel compounds was evaluated in Eca109 and Hela cell lines. Almost all the tested compounds showed manifested potent inhibitory activity against the two tested cancer cell lines. Topo I-mediated DNA relaxation activity indicated that these novel compounds have potent Topoisomerase I inhibition activity. The most potent compounds 4n and 4k demonstrated more cytotoxicity than camptothecin and was comparable to camptothecin in inhibitory activities on Topoisomerase I in our biological assay. In addition, the Hoechst 33342 staining method also showed that the complex can induce Hela cell apoptosis. PMID- 27667556 TI - The herbal medicine Cyperus amuricus inhibits proliferation of human hepatocellular carcinoma Hep3B cells by inducing apoptosis and arrest at the G0/G1 cell cycle phase. AB - Cyperus amuricus (C. amuricus) is one of the most common herbs in Oriental folk medicine for exerting astringent, diuretic, wound healing and other intestinal problems. However, little is known about the molecular mechanism of C. amuricus on anticancer activity. In the present study, the underlying mechanism of the anticancer effect of C. amuricus were elucidated. The methyl alcohol extract from the whole plant of C. amuricus exhibited cytotoxicity against Hep3B cells, but not against A549 and HaCaT cells. Consistent with an acceleration of the sub-G1 phase, downregulation of cdc25A, cyclin D1 and cyclin E, CDK4 and 2 as well as E2F-1, phospho-Rb, with concomitant of upregulation of p21CIP1/WAF1, p27KIPI and p16INK4a proteins, as evidenced by the appearance of cell cycle arrest, were detected in C. amuricus-treated Hep3B cells. Additionally, the sequential activation of various caspases (cleaved caspase-8, -9, -3, -7 and -6, and cleaved PARP) and the changed expression of other proteins related to the apoptosis pathway were observed after C. amuricus exposure. An increment in the pro apoptotic proteins (Bim, tBid, Bax and Bak) and a reduction of anti-apoptotic protein (Bcl-2) regulate Hep3B cell death by controlling the permeability of mitochondrial membranes and the release of cytochrome c from mitochondria into the cytosol with Apaf-1 after C. amuricus treatment. This is the first study indicating the potential of C. amuricus as a complementary agent for prevention and treatment of human liver cancer. PMID- 27667555 TI - Effect of geometry on deformation of anterior implant-supported zirconia frameworks: An in vitro study using digital image correlation. AB - PURPOSE: To evaluate the effect of geometry on the displacement and the strain distribution of anterior implant-supported zirconia frameworks under static load using the 3D digital image correlation method. METHODS: Two groups (n=5) of 4 unit zirconia frameworks were produced by CAD/CAM for the implant-abutment assembly. Group 1 comprised five straight configuration frameworks and group 2 consisted of five curved configuration frameworks. Specimens were cemented and submitted to static load up to 200N. Displacements were captured with two high speed photographic cameras and analyzed with video correlation system in three spacial axes U, V, W. Statistical analysis was made using the nonparametric Mann Whitney test. RESULTS: Up to 150N loads, the vertical displacements (V axis) were statistically higher for curved frameworks (-267.83+/-23.76MUm), when compared to the straight frameworks (-120.73+/-36.17MUm) (p=0.008), as well as anterior displacements in the W transformed axis (589.55+/-64.51MUm vs 224.29+/-50.38MUm for the curved and straight frameworks), respectively (p=0.008). The mean von Mises strains over the surface frameworks were statistically higher for the curved frameworks under any load. CONCLUSION: Within the limitations of this in vitro study, it is possible to conclude that the geometric configuration influences the deformation of 4-unit anterior frameworks under static load. The higher strain distribution and micro-movements of the curved frameworks reflect less rigidity and increased risk of fractures associated to FPDs. PMID- 27667557 TI - Blood-Brain Barrier Changes in High Altitude. AB - Cerebral syndromes related to high-altitude exposure are becoming more frequent as the number of trips to high altitudes has increased in the last decade. The commonest symptom is headache, followed by acute mountain sickness (AMS) and high altitude cerebral edema (HACE), which can be fatal. The pathophysiology of these syndromes is not fully understood. The classical "tight-fit hypothesis" posits that there are some anatomical variations that would obstruct the sinovenous outflow and worsen vasogenic edema and intracranial hypertension reactive to hypoxia. This could explain microhemorrhages seen in autopsies. However, recent magnetic resonance imaging studies have demonstrated some components of cytotoxic edema in HACE absent in AMS, suggesting a dysfunction in water balance at the cellular level. Currently, the "red-ox theory" supports trigemino-vascular system activation by free radicals formed after hypoxia and the consequent oxidative stress cascades. Apart from trigemino-vascular system activation, free radicals can also provoke membrane destabilisation mediated by lipid peroxidation, inflammation, and local hypoxia inducible factor-1alpha and vascular endothelial growth factor activation, resulting in gross blood-brain barrier (BBB) dysfunction. Besides alterations in endothelial cells such as increased pinocytotic vesicles and disassembly of interendothelial tight junction proteins, capillary permeability may also increase with subsequent swelling of astrocyte end-feet. In conclusion, although the pathophysiology of AMS and HACE is not completely understood, recent evidence proposes a multifactorial entity, with brain swelling and compromise of the BBB considered to play an important role. A fuller comprehension of these processes is crucial to reduce and prevent BBB alterations during high-altitude exposure. PMID- 27667558 TI - Salivary gland-like breast carcinomas: An infrequent disease. AB - OBJECTIVE: To show the incidence, as well as the clinical and histopathological characteristics, of patients diagnosed with mammary salivary gland-like carcinomas at our institution. MATERIALS AND METHODS: A retrospective study was conducted in all women diagnosed with breast cancer at our institution from January 2005 to February 2016. Patients with diagnosis of salivary gland-like breast carcinomas were included. RESULTS: In this period, 6384 patients were diagnosed with breast cancer at our institution; salivary gland-like carcinomas were found in 7 patients (0.1%), adenoid cystic carcinoma was diagnosed in 5 patients (0.07%), acinic cell carcinoma in 1 patient (0.015%) and mucoepidermoid carcinoma in 1 patient (0.015%). The triple-negative subtype was found in all of the tumors. Median follow-up was 66.3 months (range, 1-108 months). No patient developed local or distant recurrence. CONCLUSIONS: Salivary gland-like breast tumors are extremely rare. We found a global incidence of 0.1%. Adenoid cystic, acinic cell and mucoepidermoid carcinomas were the three histologic types diagnosed. Although the triple-negative subtype is mainly found, good prognosis is expected. PMID- 27667559 TI - Effects of an early intervention using human amniotic epithelial cells in a COPD rat model. AB - The study aimed to investigate the effect of an early intervention using human amniotic epithelial cell (hAEC) in a rat model of chronic obstructive pulmonary disease (COPD). Twenty-four specific pathogen-free Wistar rats were randomized to the control, COPD, and COPD+hAEC groups. COPD was established by intratracheal LPS injection combined with smoke fumigation over 30days. On the first day of model establishment rats in the AEC group also received intratracheal instillation of 500,000 hAECs isolated from the placenta of healthy donors. The mean linear intercept (MLI) and mean alveolar number (MAN) were used to assess the degree of lung emphysema. IL-8 was measured using a radioimmunoassay, surfactant protein D (SP-D) was measured by ELISA, and matrix metalloproteinase (MMP)2 and MMP8 expression was assessed by PCR. Smoke fumigation combined to LPS injection successfully established a COPD rat model with significant emphysema and airway inflammation, elevated MLI and MAN, elevated systemic and lung tissue levels of IL-8 and SP-D (P<0.05), and high expression of MMP2 and MMP8. Rats in the COPD+hAEC group exhibited alleviated lung damage, MLI and MAN (P<0.05), reduced systemic and lung tissue levels of IL-8 and SP-D (P<0.05) and MMP2 and MMP8 expression (P<0.05). Early intervention using hAECs could delay disease progression in rats with COPD. PMID- 27667560 TI - Systematic Identification of Pharmacological Targets from Small-Molecule Phenotypic Screens. AB - Phenotypic drug discovery offers some advantages over target-based methods, mainly because it allows drug leads to be tested in systems that more closely model distinct disease states. However, a potential disadvantage is the difficulty of linking the observed phenotype to a specific cellular target. To address this problem, we developed DePick, a computational target de-convolution tool to determine targets specifically linked to small-molecule phenotypic screens. We applied DePick to eight publicly available screens and predicted 59 drug target-phenotype associations. In addition to literature-based evidence for our predictions, we provide experimental support for seven predicted associations. Interestingly, our analysis led to the discovery of a previously unrecognized connection between the Wnt signaling pathway and an aromatase, CYP19A1. These results demonstrate that the DePick approach can not only accelerate target de-convolution but also aid in discovery of new functionally relevant biological relationships. PMID- 27667562 TI - Developing a valid meal assessment tool for hospital patients. AB - Patients' perspectives of meal items are critical in supporting effective decisions about meal provision in hospitals. The objective of this research was to develop a valid meal assessment tool (MAT), to quickly and accurately assess patient's views on meal items, for ultimate use in a large multi-centre trial. Nine iterations of the meal assessment tool were tested for content and construct validity in a large acute care hospital to determine wording, number scale and physical orientation for responses. Patients were interviewed to assess content validity, ease of completion, timing and assistance requirement. Following expert feedback, the resulting tool consisted of a 7 point scale measuring three meal components (meat, starch and vegetable), with ratings for flavour and taste combined, appearance and quality. Measures of overall satisfaction, meal expectation, age and gender were included for direct comparability with the valid published Acute Care Hospital Foodservice Patient Satisfaction Questionnaire (ACHFPSQ). Three hundred and four surveys were completed in the development process (77% response), 53% male, mean age 56 years. Best completion rates were by interview with completion times of 2-5 min. The tool was then made available in a large multi-centre meal assessment project (n = 14,500) and was able to detect differences between variations of the same meal and between the same ingredient prepared in alternative ways. The MAT proved successful in discriminating meal components in terms of quality, taste and appearance and is useful for those planning and assessing meals in a variety of healthcare settings. PMID- 27667561 TI - Small-Molecule Chemical Probe Rescues Cells from Mono-ADP-Ribosyltransferase ARTD10/PARP10-Induced Apoptosis and Sensitizes Cancer Cells to DNA Damage. AB - Members of the human diphtheria toxin-like ADP-ribosyltransferase (ARTD or PARP) family play important roles in regulating biological activities by mediating either a mono-ADP-ribosylation (MARylation) of a substrate or a poly-ADP ribosylation (PARylation). ARTD10/PARP10 belongs to the MARylating ARTDs (mARTDs) subfamily, and plays important roles in biological processes that range from cellular signaling, DNA repair, and cell proliferation to immune response. Despite their biological and disease relevance, no selective inhibitors for mARTDs are available. Here we describe a small-molecule ARTD10 inhibitor, OUL35, a selective and potent inhibitor for this enzyme. We characterize its selectivity profile, model its binding, and demonstrate activity in HeLa cells where OUL35 rescued cells from ARTD10 induced cell death. Using OUL35 as a cell biology tool we show that ARTD10 inhibition sensitizes the cells to the hydroxyurea-induced genotoxic stress. Our study supports the proposed role of ARTD10 in DNA-damage repair and provides a tool compound for selective inhibition of ARTD10-mediated MARylation. PMID- 27667563 TI - Traditional food uses of wild plants among the Gorani of South Kosovo. AB - A food ethnobotanical field study was conducted among the Gorani of South Kosovo, a small ethnic minority group that speaks a South-Slavic language and lives in the south of the country. We conducted forty-one semi-structured interviews in ten villages of the Kosovar Gora mountainous area and found that seventy-nine wild botanical and mycological taxa represent the complex mosaic of the food cultural heritage in this population. A large portion of the wild food plant reports refer to fermented wild fruit-based beverages and herbal teas, while the role of wild vegetables is restricted. A comparison of these data with those previously collected among the Gorani living in nearby villages within the territory of Albania, who were separated in 1925 from their relatives living in present-day Kosovo, shows that approximately one third of the wild food plant reports are the same. This finding demonstrates the complex nature of Kosovar Gorani ethnobotany, which could indicate the permanence of possible "original" Gorani wild plant uses (mainly including wild fruits-based beverages), as well as elements of cultural adaptation to Serbian and Bosniak ethnobotanies (mainly including a few herbal teas and mushrooms). PMID- 27667564 TI - Miltefosine inhibits Candida albicans and non-albicans Candida spp. biofilms and impairs the dispersion of infectious cells. AB - Candida spp. can adhere to and form biofilms over different surfaces, becoming less susceptible to antifungal treatment. Resistance of biofilms to antifungal agents is multifactorial and the extracellular matrix (ECM) appears to play an important role. Among the few available antifungals for treatment of candidaemia, only the lipid formulations of amphotericin B (AmB) and the echinocandins are effective against biofilms. Our group has previously demonstrated that miltefosine has an important effect against Candida albicans biofilms. Thus, the aim of this work was to expand the analyses of the in vitro antibiofilm activity of miltefosine to non-albicans Candida spp. Miltefosine had significant antifungal activity against planktonic cells and the development of biofilms of C. albicans, Candida parapsilosis, Candida tropicalis and Candida glabrata. The activity profile in biofilms was superior to fluconazole and was similar to that of AmB and caspofungin. Biofilm-derived cells with their ECM extracted became as susceptible to miltefosine as planktonic cells, confirming the importance of the ECM in the biofilm resistant behaviour. Miltefosine also inhibited biofilm dispersion of cells at the same concentration needed to inhibit planktonic cell growth. The data obtained in this work reinforce the potent inhibitory activity of miltefosine on biofilms of the four most pathogenic Candida spp. and encourage further studies for the utilisation of this drug and/or structural analogues on biofilm-related infections. PMID- 27667565 TI - Alarming increase in prevalence of Neisseria gonorrhoeae infections associated with a high level of antibiotic resistance in Tripoli, Lebanon. PMID- 27667567 TI - A novel regulatory relationship between RIPK4 and ELF3 in keratinocytes. AB - Keratinocytes are central to the barrier functions of surface epithelia, such as the gingiva and epidermis. RIPK4 is a key regulator of keratinocyte differentiation; however, the signalling pathways in which it functions remain poorly defined. In this study, we identified a regulatory relationship between RIPK4 and ELF3, an ETS family transcription factor. RIPK4 was shown to be important for the upregulation of ELF3 gene expression by the PKC agonist PMA in both oral and epidermal keratinocytes. RIPK4 promotes keratinocyte differentiation in part by phosphorylating and thereby activating the IRF6 transcription factor. Significantly, silencing of IRF6 inhibited the PMA inducible expression of ELF3. A role for the GRHL3 transcription factor, a downstream target gene of IRF6, in the regulation of ELF3 expression was similarly demonstrated. ELF3 has previously been shown to regulate the expression of SPPR1A and SPRR1B, small proline-rich proteins that contribute to the cornification of keratinocytes. Consistently, RIPK4 and IRF6 were important for the PMA-inducible expression of SPRR1A and SPRR1B. They were also important for the upregulation of TGM1, a transglutaminase that catalyses the cross-linking of proteins, including small proline-rich proteins, during keratinocyte cornification. RIPK4 was also shown to upregulate the expression of TGM2 independently of IRF6. Collectively, our findings position RIPK4 upstream of a hierarchal IRF6-GRHL3-ELF3 transcription factor pathway in keratinocytes, as well as provide insight into a potential role for RIPK4 in the regulation of keratinocyte cornification. PMID- 27667566 TI - Role of End Binding Protein-1 in endothelial permeability response to barrier disruptive and barrier-enhancing agonists. AB - Rapid changes in microtubule (MT) polymerization dynamics affect regional activity of small GTPases RhoA and Rac1, which play a key role in the regulation of actin cytoskeleton and endothelial cell (EC) permeability. This study tested the role of End Binding Protein-1 (EB1) in the mechanisms of increased and decreased EC permeability caused by thrombin and hepatocyte growth factor (HGF) and mediated by RhoA and Rac1 GTPases, respectively. Stimulation of human lung EC with thrombin inhibited peripheral MT growth, which was monitored by morphological and biochemical evaluation of peripheral MT and the levels of stabilized MT. In contrast, stimulation of EC with HGF promoted peripheral MT growth and protrusion of EB1-positive MT plus ends to the EC peripheral submembrane area. EB1 knockdown by small interfering RNA did not affect partial MT depolymerization, activation of Rho signaling, and permeability response to thrombin, but suppressed the HGF-induced endothelial barrier enhancement. EB1 knockdown suppressed HGF-induced activation of Rac1 and Rac1 cytoskeletal effectors cortactin and PAK1, impaired HGF-induced assembly of cortical cytoskeleton regulatory complex (WAVE-p21Arc-IQGAP1), and blocked HGF-induced enhancement of peripheral actin cytoskeleton and VE-cadherin-positive adherens junctions. Altogether, these data demonstrate a role for EB1 in coordination of MT-dependent barrier enhancement response to HGF, but show no involvement of EB1 in acute increase of EC permeability caused by the barrier disruptive agonist. The results suggest that increased peripheral EB1 distribution is a critical component of the Rac1-mediated pathway and peripheral cytoskeletal remodeling essential for agonist-induced EC barrier enhancement. PMID- 27667568 TI - Inundation of asthma target research: Untangling asthma riddles. AB - Asthma is an inveterate inflammatory disorder, delineated by the airway inflammation, bronchial hyperresponsiveness (BHR) and airway wall remodeling. Although, asthma is a vague term, and is recognized as heterogenous entity encompassing different phenotypes. Targeting single mediator or receptor did not prove much clinical significant, as asthma is complex disease involving myriad inflammatory mediators. Asthma may probably involve a large number of different types of molecular and cellular components interacting through complex pathophysiological pathways. This review covers the past, present, and future therapeutic approaches and pathophysiological mechanisms of asthma. Furthermore, review describe importance of targeting several mediators/modulators and receptor antagonists involved in the physiopathology of asthma. Novel targets for asthma research include Galectins, Immunological targets, K + Channels, Kinases and Transcription Factors, Toll-like receptors, Selectins and Transient receptor potential channels. But recent developments in asthma research are very promising, these include Bitter taste receptors (TAS2R) abated airway obstruction in mouse model of asthma and Calcium-sensing receptor obliterate inflammation and in bronchial hyperresponsiveness allergic asthma. All these progresses in asthma targets, and asthma phenotypes exploration are auspicious in untangling of asthma riddles. PMID- 27667569 TI - Migratory blackcaps can use their magnetic compass at 5 degrees inclination, but are completely random at 0 degrees inclination. AB - It is known that night-migratory songbirds use a magnetic compass measuring the magnetic inclination angle, i.e. the angle between the Earth's surface and the magnetic field lines, but how do such birds orient at the magnetic equator? A previous study reported that birds are completely randomly oriented in a horizontal north-south magnetic field with 0 degrees inclination angle. This seems counter-intuitive, because birds using an inclination compass should be able to separate the north-south axis from the east-west axis, so that bimodal orientation might be expected in a horizontal field. Furthermore, little is known about how shallow inclination angles migratory birds can still use for orientation. In this study, we tested the magnetic compass orientation of night migratory Eurasian blackcaps (Sylvia atricapilla) in magnetic fields with 5 degrees and 0 degrees inclination. At 5 degrees inclination, the birds oriented as well as they did in the normal 67 degrees inclined field in Oldenburg. In contrast, they were completely randomly oriented in the horizontal field, showing no sign of bimodality. Our results indicate that the inclination limit for the magnetic compass of the blackcap is below 5 degrees and that these birds indeed seem completely unable to use their magnetic compass for orientation in a horizontal magnetic field. PMID- 27667571 TI - An antidote to fluorouracil and capecitabine toxicity. PMID- 27667570 TI - Osteoblast Differentiation at a Glance. AB - Ossification is a tightly regulated process, performed by specialized cells called osteoblasts. Dysregulation of this process may cause inadequate or excessive mineralization of bones or ectopic calcification, all of which have grave consequences for human health. Understanding osteoblast biology may help to treat diseases such as osteogenesis imperfecta, calcific heart valve disease, osteoporosis, and many others. Osteoblasts are bone-building cells of mesenchymal origin; they differentiate from mesenchymal progenitors, either directly or via an osteochondroprogenitor. The direct pathway is typical for intramembranous ossification of the skull and clavicles, while the latter is a hallmark of endochondral ossification of the axial skeleton and limbs. The pathways merge at the level of preosteoblasts, which progress through 3 stages: proliferation, matrix maturation, and mineralization. Osteoblasts can also differentiate into osteocytes, which are stellate cells populating narrow interconnecting passages within the bone matrix. The key molecular switch in the commitment of mesenchymal progenitors to osteoblast lineage is the transcription factor cbfa/runx2, which has multiple upstream regulators and a wide variety of targets. Upstream is the Wnt/Notch system, Sox9, Msx2, and hedgehog signaling. Cofactors of Runx2 include Osx, Atf4, and others. A few paracrine and endocrine factors serve as coactivators, in particular, bone morphogenetic proteins and parathyroid hormone. The process is further fine-tuned by vitamin D and histone deacetylases. Osteoblast differentiation is subject to regulation by physical stimuli to ensure the formation of bone adequate for structural and dynamic support of the body. Here, we provide a brief description of the various stimuli that influence osteogenesis: shear stress, compression, stretch, micro- and macrogravity, and ultrasound. A complex understanding of factors necessary for osteoblast differentiation paves a way to introduction of artificial bone matrices. PMID- 27667572 TI - Antiemetic overuse in patients receiving chemotherapy. PMID- 27667573 TI - Lazic Aneurysm Clip System for Microsurgical Clipping of Cerebral Aneurysms: Transition to a New Aneurysm Clip System in an Established Cerebrovascular Practice. AB - BACKGROUND: In an era of continued advancements in endovascular treatment of cerebral aneurysms, novel developments concerning microsurgical clipping are sparse. The Lazic aneurysm clip system represents such an advancement. The applier has a malleable shaft and is designed to minimally obstruct the view of the surgical field. The purpose of this study was to illustrate the transition to this new aneurysm clip system in an established cerebrovascular practice. METHODS: We retrospectively reviewed all aneurysms treated with microsurgical clipping using the Lazic aneurysm clip system in 1 cerebrovascular practice in the United States from January 2009 to June 2016. RESULTS: Between 2009 and 2016, a total of 973 aneurysms underwent surgical clipping. The Lazic clip system was used in 191 (19.6%) aneurysms (maximum diameter, 5.6 +/- 3.8 mm) in 181 patients. The middle cerebral artery was the most frequent location (25.7%) followed by posterior communicating artery (20.9%). There was a continuous increase in the percentage of aneurysms treated with the Lazic clip system from 6% in 2009 to 98% in 2016. The proportion of posterior circulation aneurysms treated with Lazic clips decreased, whereas the middle cerebral artery location increased. There were a total of 11 complications (5.8%), but no instances of clip malfunction. CONCLUSIONS: In the largest series to date, the Lazic clip system proved to be safe and efficacious and presents an interesting alternative to established aneurysm clip systems. This study illustrates the transition of an established cerebrovascular practice to the Lazic clip system. PMID- 27667574 TI - Intracranial Angiomatoid Fibrous Histiocytoma: Case Report and Literature Review. AB - BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare and low-grade soft tissue lesion that typically arises from subcutaneous and deep dermal tissue of extremities. The first case was reported in 1979 by Enzinger and has since become known as a distinct entity. AFH has been increasingly reported in different organ systems, with rare reports of primary intracranial AFH. To date there have been 3 reports of intracranial AFH and 1 report of metastasis to the brain, most of which were in young adults. CASE DESCRIPTION: In this paper, we present a case of an older patient with a large, petrous apex AFH that was clinically mistaken for a trigeminal nerve schwannoma. We discuss radiographic and histologic features initially found and the findings that ultimately led to the diagnosis of AFH. We also discuss the findings noted in all other reports of intracranial AFH. CONCLUSION: We present a rare case of intracranial AFH in a patient relatively old for onset of diagnosis. To date, only 3 prior cases of AFH have been reported. The radiographic findings were nonspecific and initially pointed toward a diagnosis of schwannoma, whereas histopathology seemed to initially suggest meningioma. Further pathologic consultation finally confirmed AFH as the diagnosis. We suspect there are more cases of intracranial AFH that are misdiagnosed due to variability of findings on pathology. The behavior of this tumor remains in question as 1 of the 3 reported cases demonstrated significant recurrence. As such, gross total resection of this lesion is preferable. PMID- 27667575 TI - Impact of the Economic Downturn on Elective Cervical Spine Surgery in the United States: A National Trend Analysis, 2003-2013. AB - OBJECTIVE: To analyze overall trends of elective cervical spine surgery in the United States from 2003 to 2013 with the goal of determining whether the economic downturn had an impact. METHODS: Codes from the International Classification of Diseases, Ninth Revision, Clinical Modification were used to identify elective cervical spine surgery procedures in the Nationwide Inpatient Sample from 2003 to 2013. National Health Expenditure, gross domestic product, and S&P 500 Index were used as measures of economic performance. The economic downturn was defined as 2008-2009. Confidence intervals were determined using subgroup analysis techniques. Linear regressions were completed to determine the association between surgery trends and economic conditions. RESULTS: From 2003 to 2013, posterior cervical fusions saw a 102.7% increase. During the same time frame, there was a 7.4% and 14.7% decrease in the number of anterior cervical diskectomy and fusions (ACDFs) and posterior decompressions, respectively. The trend of elective cervical spine surgeries per 100,000 persons in the U.S. population may have been affected by the economic downturn from 2008 to 2009 (-0.03% growth). The percentage of procedures paid for by private insurance decreased from 2003 to 2013 for all ACDFs, posterior cervical fusions, and posterior decompressions. The linear regression coefficients (beta) and R2 values between the number of surgeries and each of the macroeconomic factors analyzed were not statistically significant. CONCLUSIONS: The overall elective cervical spine surgery trend was not likely impacted by the economic downturn. Posterior cervical fusions grew significantly from 2003 to 2013, whereas ACDFs and posterior decompressions decreased. PMID- 27667576 TI - Inexpensive Attachment Device for Cell Therapy Administration into Injured Spinal Cord. AB - BACKGROUND: Cell therapy is configured as a promising strategy for the treatment of spinal cord injury (SCI), but it requires reliable systems to achieve microinjections with different rates and volumes, according to the different characteristics of the injured spinal cord tissue and the targets previously selected. OBJECTIVE: We sought to describe an original and inexpensive device for support of microinjection systems in the course of spinal cord surgery. METHODS: Our attachment device consists of an arch and a system of bars that can be fixed to the operating table and on which a microinjection pump can be displaced and fixed in the course of surgery. RESULTS: This device has been used for therapy administration into injured spinal cords. It is easy to use and permits reproducible results. CONCLUSION: We have described an original attachment device for the support of a microinjection pump. It is applicable to spinal cord surgery and should be considered as a cheap solution for intralesional administration of cell therapy after spinal cord injury. PMID- 27667577 TI - Brain Metastases: Surgical Treatment and Overall Survival. AB - BACKGROUND: Brain metastases occur in 10%-40% of patients with cancer and are more common than primary brain tumors (30%-40%); their incidence is growing because of improvements in control of systemic disease, better radiologic detection, and prolonged survival. Modern treatment of brain metastases has dramatically changed the expected prognosis. Traditionally, the prognosis has been considered very poor, and patients were referred to palliative treatment because of their terminal stage; however, new prognostic indexes have been proposed to evaluate these patients. The aim of our study was to determine the long-term effect of surgery on overall survival (OS) in patients with brain metastases from dissimilar primary tumors and to identify prognostic variables associated with prolonged survival. METHODS: We retrospectively reviewed a consecutive series of patients who underwent surgery between January 2010 and October 2014 for cerebral metastases from lung, kidney, breast, and gastrointestinal cancers and melanoma. Variables included age; sex; histology; location of lesions; and specific treatments patients had undergone including chemotherapy, radiotherapy, and surgery, individually or combined. RESULTS: No patients deteriorated after surgery. At discharge, 19 patients (26.76%) had an unchanged postoperative neurologic examination, whereas 52 patients (73.23%) showed improvement (chi2 = 34.84, P < 0.0001). Expected OS, considering all tumor subtypes, was 372.24 months; the patients in our series had an OS of 787 months, more than twice the expected OS; specifically, average expected survival of each patient was 5.24 months, whereas actual survival was 11.08 months (P = 0.000008). CONCLUSIONS: Surgery is a safe and effective procedure for cerebral metastases and should not be considered an aggressive treatment in such disease. In our series, 55% of patients had a survival >6 months and a significant improvement in terms of actual versus expected survival. Surgical resection should be considered the primary option for patients with brain metastases. PMID- 27667578 TI - Impact of Intraoperative Steroids on Postoperative Infection Rates and Length of Hospital Stay: A Study of 1200 Spine Surgery Patients. AB - OBJECTIVE: The use of intraoperative steroids and their effects are relatively unknown and remain controversial. The aim of this study was to determine the effects of intraoperative steroid use on postoperative complications and length of hospital stay after spine surgery. METHODS: Medical records of 1200 adult patients undergoing spine surgery at Duke University Medical Center during the period 2008-2010 were retrospectively reviewed; 495 (41.25%) patients were administered intraoperative steroids, and 705 (58.75%) patients were not administered intraoperative steroids. Patient demographics, comorbidities, and postoperative complication rates were collected. The primary outcomes investigated were postoperative complications, specifically length of hospital stay and infection rates. RESULTS: Patient demographics were similar between both cohorts. Comorbidities were also similar, with the intraoperative steroid use cohort having a higher number of patients with long-term steroid use than the no intraoperative steroid use cohort (6.95% [no steroids] vs. 13.74% [steroid use], P < 0.001). Operative variables, including length of operation and median number of fusion levels operated, were also similar between the 2 groups. Lumbar spine was the most common surgical location. Patients who were administered intraoperative steroids had a shorter length of hospital stay by an average of 1 day (6.06 days +/- 6.76 [no steroids] vs. 5.04 days +/- 4.86 [steroid use], P = 0.0025), lower rates of urinary tract infections (10.37% [no steroids] vs. 6.88% [steroid use], P = 0.040), and lower rates of other infections that were not deep or superficial surgical site infections (9.22% [no steroids] vs. 6.06% [steroid use], P = 0.0460). CONCLUSIONS: Patients who receive intraoperative steroids have shorter hospital stays and lower infection rates after spine surgery. PMID- 27667581 TI - Plant derived anti-cancerous secondary metabolites as multipronged inhibitor of COX, Topo, and aromatase: molecular modeling and dynamics simulation analyses. AB - In the present study, 300 plant derived secondary metabolites (100 each of alkaloid, flavonoid, and terpenoid), have been screened for their anti-cancerous activity through inhibition of selected key enzymatic targets, namely cyclooxygenases (COXs), topoisomerases (Topos), and aromatase by molecular docking approach. Furthermore, the stability of the complexes of top hits, from each class of secondary metabolites, with their respective enzymatic targets was analyzed using molecular dynamics (MD) simulation analyses and binding free energy calculations. Analysis of the results of the docking in light of the pharmacokinetically screened 18 alkaloids, 26 flavonoids, and 9 terpenoids, revealed that the flavonoid, curcumin, was the most potent inhibitor for all the selected enzymatic targets. The stability of the complexes of COX-1, COX-2, Topo I, Topo IIbeta and aromatase with the most potent inhibitor curcumin and those of the respective drugs, namely ibuprofen, aspirin, topotecan, etoposide, and exemestane were also analyzed through MD simulation analyses which revealed better stability of curcumin complexes than those of respective drugs. Binding energy calculations of the complexes of the curcumin with all the targets, except those of Topos, exhibited lower binding energies for the curcumin complexes than those of respective drugs which corroborated with the results of molecular docking analyses. Thus, the present study affirms the versatile and multipronged nature of curcumin, the traditionally used herbal medicine, as anti-cancer molecule directed against these enzymatic targets. PMID- 27667580 TI - Insights into the pathogenesis of Mycoplasma pneumoniae (Review). AB - Mycoplasma are the smallest prokaryotic microbes present in nature. These wall less, malleable organisms can pass through cell filters, and grow and propagate under cell-free conditions in vitro. Of the pathogenic Mycoplasma Mycoplasma pneumoniae has been examined the most. In addition to primary atypical pneumonia and community-acquired pneumonia with predominantly respiratory symptoms, M. pneumoniae can also induce autoimmune hemolytic anemia and other diseases in the blood, cardiovascular system, gastrointestinal tract and skin, and can induce pericarditis, myocarditis, nephritis and meningitis. The pathogenesis of M. pneumoniae infection is complex and remains to be fully elucidated. The present review aimed to summarize several direct damage mechanisms, including adhesion damage, destruction of membrane fusion, nutrition depletion, invasive damage, toxic damage, inflammatory damage and immune damage. Further investigations are required for determining the detailed pathogenesis of M. pneumoniae. PMID- 27667582 TI - Expression and analyses of the HIF-1 pathway in the lungs of humans with pulmonary arterial hypertension. AB - Pulmonary arterial hypertension (PAH) is characterized by endothelial dysfunction and structural remodeling of the pulmonary vasculature, mediated initially by reduced oxygen availability in the lungs. Hypoxia inducible factor (HIF), consisting of the functional subunit, HIF-1alpha, and the constitutively expressed HIF-1beta, is involved in the pathological processes associated with hypoxia. In the current study, the sequences of cDNAs and amino acids of HIF were characterized and analyzed using online bioinformatics tools. To further evaluate whether HIF accounts for the occurrence of PAH, the present study determine the expression and phosphorylation levels of HIF and its associated pathways, including extracellular signal-regulated kinase (Erk)1/2 and phosphoinositide 3 kinase (PI3K)/Akt, in the lungs of patients with PAH by reverse transcription quantitative polymerase chain reaction and western blotting. The mRNA expression levels of PI3K, Erk2, and HIF-1alpha in the patients with PAH were significantly higher, compared with those in the control group, by 3.6-fold (P<0.01), 4.06-fold and 2.64-fold (P<0.05), respectively. No significant differences were found in the mRNA and protein levels of Akt between the two groups (P>0.05). The protein levels of phosphorylated (p-)Akt, Erk1/2, p-Erk1/2, HIF-1alpha and HIF-1beta were significantly increased by 5.89-, 0.5-, 0.59-, 1.46- and 0.92-fold, respectively, in the patients with PAH, compared with those in the controls group (P<0.01 for p Akt, Erk1/2; P<0.05 for p-Erk1/2, HIF-1alpha and HIF-1beta). These findings suggested that the mitogen-activated protein kinase and PI3K/Akt signaling pathways, and HIF-1 may perform a specific function in the pathogenesis of PAH. PMID- 27667579 TI - IBS and IBD - separate entities or on a spectrum? AB - The acute phase of IBD with inflamed gut and often ulcerated mucosa is clearly different from the apparently normal mucosa characteristic of IBS. However, more detailed assessment has detected immune activation, increased gut permeability, increased mucosal serotonin availability, abnormalities of enteric nerve structure and function, and dysbiosis in gut microbiota in IBS - all features seen in IBD. Furthermore, as treatments for inflammation in IBD have become more effective it is now apparent that ~1 in 3 patients with IBD in remission from inflammation still have persistent abnormalities of sensation, motility and gut microbiota, which might cause IBS-like symptoms. This Perspective explores the overlap between IBS and IBD and their treatments, proposing future directions for research in this stimulating area. PMID- 27667583 TI - Fast generations of tree-type three-dimensional entanglement via Lewis-Riesenfeld invariants and transitionless quantum driving. AB - Recently, a novel three-dimensional entangled state called tree-type entanglement, which is likely to have applications for improving quantum communication security, was prepared via adiabatic passage by Song et al. Here we propose two schemes for fast generating tree-type three-dimensional entanglement among three spatially separated atoms via shortcuts to adiabatic passage. With the help of quantum Zeno dynamics, two kinds of different but equivalent methods, Lewis-Riesenfeld invariants and transitionless quantum driving, are applied to construct shortcuts to adiabatic passage. The comparisons between the two methods are discussed. The strict numerical simulations show that the tree-type three dimensional entangled states can be fast prepared with quite high fidelities and the two schemes are both robust against the variations in the parameters, atomic spontaneous emissions and the cavity-fiber photon leakages. PMID- 27667584 TI - Design, Synthesis and Evaluation of Novel Isoxazolines/Oxime Sulfonates of 2'(2',6')-(Di)Chloropodophyllotoxins as Insecticidal Agents. AB - A series of 2'(2',6')-(di)halogeno-isoxazolopodophyllic acids-based esters, and oxime sulfonates of 2'(2',6')-(di)halogenopodophyllones were prepared by structural modifications of podophyllotoxin as insecticidal agents against Mythimna separata Walker. It was found that when 2'(2',6') (di)halogenopodophyllones or 2'(2',6')-(di)chloropicropodophyllones reacted with hydroxylamine hydrochloride, the desired products were related with the configuration of their lactones. Three key single-crystal structures of Ie, IIe and IIIb were determined by X-ray diffraction. Especially compounds IIc and Vc showed the highest insecticidal activity. Moreover, some interesting results of structure-insecticidal activity relationships of tested compounds were also observed. PMID- 27667585 TI - Influence of mealtime habits on the risk of weight gain and obesity in Mexican adults. AB - OBJECTIVE: To prospectively examine the extent to which mealtime habits influences the risk of weight gain and obesity in Mexican adults. DESIGN: We performed a prospective cohort study. The Mealtime Habits Quality (MHQ) scale was used for assessing participants' MHQ; the outcomes of interest were gain >=5 % of body weight, developing overweight/obesity and abdominal obesity, after 7 years of follow-up. In order to estimate the independent effect of MHQ on anthropometric indicators, generalized linear models were computed to obtain adjusted relative risks (95 % CI). SETTING: The state of Morelos, Mexico. SUBJECTS: Mexican adults (n 837) aged 18-70 years participating in a cohort study. RESULTS: Compared with participants classified in the higher MHQ category, individuals in the middle and lower MHQ groups had a 4.1 (2.5, 6.7) and 6.2 (3.9, 9.7) fold greater risk of gain >=5 % of body weight, respectively; 6.6 (2.8, 15.5) and 8.6 (3.7, 19.8) fold greater risk of becoming overweight/obese, respectively; and 3.8 (2.0, 7.3) and 5.3 (2.8, 9.8) fold greater risk of developing abdominal obesity, respectively. CONCLUSIONS: This study provides evidence about the influence of a set of mealtime habits on obesity indicators, showing that greater adherence to unadvisable mealtime habits increases the risk of developing unhealthy anthropometric indicators. Since the meal is one of the most important sources of food intake, and consequently weight status, the MHQ scale can be a useful population tool to predict weight gain and obesity. PMID- 27667586 TI - Biosafety standards for working with Crimean-Congo hemorrhagic fever virus. AB - In countries from which Crimean-Congo haemorrhagic fever (CCHF) is absent, the causative virus, CCHF virus (CCHFV), is classified as a hazard group 4 agent and handled in containment level (CL)-4. In contrast, most endemic countries out of necessity have had to perform diagnostic tests under biosafety level (BSL)-2 or 3 conditions. In particular, Turkey and several of the Balkan countries have safely processed more than 100 000 samples over many years in BSL-2 laboratories. It is therefore advocated that biosafety requirements for CCHF diagnostic procedures should be revised, to allow the tests required to be performed under enhanced BSL-2 conditions with appropriate biosafety laboratory equipment and personal protective equipment used according to standardized protocols in the countries affected. Downgrading of CCHFV research work from CL-4, BSL-4 to CL-3, BSL-3 should also be considered. PMID- 27667587 TI - Expression pattern of CD55 and CD59 on red blood cells in sickle cell disease. AB - OBJECTIVES: To investigate the pattern of CD55 and CD59 expression on RBCs of SCD patients, and its association with anemia, biochemical parameters of hemolysis, level of erythropoietin, and pro-inflammatory markers. METHODS: Flow cytometric analysis was performed on RBCs from 71 adult SCD patients and 53 healthy controls, using the commercial REDQUANT kit. RESULTS: CD59 deficiency was significantly higher among SCD patients than among healthy controls. The proportions of CD55-deficient and CD59-deficient RBCs from SCD patients were significantly higher when compared with those from healthy controls (0.17 vs. 0.09 and 2.1 vs. 1.2, respectively). The MFI of CD55 and CD59 expression on RBCs in SCD was significantly reduced when compared to the expression in healthy controls (5.2 vs. 6.4 and 19.4 vs 20.3, respectively). The pattern of CD55 and CD59 expression was not correlated with anemia, biomarkers of hemolysis, erythropoietin level, or other pro-inflammatory markers. DISCUSSION: There is an altered pattern of CD55 and CD59 expression on RBCs of SCD Patients; however, it does not seem to play a causal role in the pathophysiology of anemia, and is unlikely to be influenced by the level of erythropoietin or other inflammatory mediators. PMID- 27667590 TI - The move to health. AB - Let's give credit where it is due. The Government's Green Paper on health targets, 'The Health of the Nation', is one of the best reports to emerge from the Health Department for some time. The targets have been widely welcomed, with even the opposition grudgingly lending its support to a Government initiative which will work toward a healthier future. PMID- 27667591 TI - Green paper. AB - Health promotion was pushed to the top of the political agenda last week following the launch of the Green Paper on the health of the English nation. PMID- 27667588 TI - Proteomic Analysis of Non-depleted Serum Proteins from Bottlenose Dolphins Uncovers a High Vanin-1 Phenotype. AB - Targeted approaches have been widely used to help explain physiological adaptations, but few studies have used non-targeted omics approaches to explore differences between diving marine mammals and terrestrial mammals. A rank comparison of undepleted serum proteins from common bottlenose dolphins (Tursiops truncatus) and pooled normal human serum led to the discovery of 11 proteins that appeared exclusive to dolphin serum. Compared to the comprehensive human plasma proteome, 5 of 11 serum proteins had a differential rank greater than 200. One of these proteins, Vanin-1, was quantified using parallel reaction monitoring in dolphins under human care and free-ranging dolphins. Dolphin serum Vanin-1 ranged between 31-106 MUg/ml, which is 20-1000 times higher than concentrations reported for healthy humans. Serum Vanin-1 was also higher in dolphins under human care compared to free-ranging dolphins (64 +/- 16 vs. 47 +/- 12 MUg/ml P < 0.05). Vanin-1 levels positively correlated with liver enzymes AST and ALT, and negatively correlated with white blood cell counts and fibrinogen in free-ranging dolphins. Major differences exist in the circulating blood proteome of the bottlenose dolphin compared to terrestrial mammals and exploration of these differences in bottlenose dolphins and other marine mammals may identify veiled protective strategies to counter physiological stress. PMID- 27667589 TI - Coalescence of Immiscible Liquid Metal Drop on Graphene. AB - Molecular dynamics simulations were performed to investigate the wetting and coalescence of liquid Al and Pb drops on four carbon-based substrates. We highlight the importance of the microstructure and surface topography of substrates in the coalescence process. Our results show that the effect of substrate on coalescence is achieved by changing the wettability of the Pb metal. Additionally, we determine the critical distance between nonadjacent Al and Pb films required for coalescence. These findings improve our understanding of the coalescence of immiscible liquid metals at the atomistic level. PMID- 27667593 TI - Managers instructed to speed appeals backlog. AB - Managers must take a 'fresh look' at grading appeals and use their own discretion and judgement to clear the backlog, both Management and Staff Side agreed at a Whitley Council meeting last Friday. PMID- 27667592 TI - ? AB - Smiles of relief: A mission to bring aid to Kurdish refugees brought nurse, John Pohorely (pictured left) and charity worker Richard Worries (centre) to the Allied Forces 'safe haven' in Zakho, Northern Iraq. They took with them a major new breakthrough in water purification. The trip was organised by the Jubilee Campaign charity. Director Danny Smith (pictured right) and Nursing Standard's Editor Norah Casey were there to greet them on their return. PMID- 27667594 TI - Cumberlege criticises NHS 'chauvinism'. AB - NHS Policy Board member Baroness Cumberlege has criticised 'chauvinism' and 'endless obstructions' within the NHS which prevent nurses from becoming full partners in general practice. PMID- 27667595 TI - RCN warns of variations in vocational standards. AB - The 'extremely hurried' consultation on proposals for a set of 12 new vocational qualifications for health workers may lead to inconsistencies in national standards, the RCN has warned in its response to the Care Sector Consortium. PMID- 27667596 TI - ? AB - Sound approach: The RCN's Jane Williamson, and Jo Cotterell from the National Dairy Council, are pictured recording the second Sound Nutrition audio tape for community nurses, launched last week. PMID- 27667597 TI - UKCC. AB - The number of under 25-year-olds entering nursing is falling, the latest statistics from the United Kingdom Central Council show. Despite an increase of almost 4 per cent in the number of nurses, midwives and health visitors between 1988 and 1990, there was a fall in the number of practitioners under 25. It is nothing that was not anticipated from the demographic trends that were there for all to see,' said Reg Pyne, UKCC Assistant Registrar Standards and Ethics. PMID- 27667599 TI - Prisons must overcome 'irrational attitudes'. AB - British prisons are 'AIDS-phobic' and need urgent strategies to prevent inmates becoming infected with HIV, says Len Curran, the Chair of the Home Office AIDS Advisory Committee. PMID- 27667598 TI - 'Bring back matron' call from select committee. AB - Nurse managers have been severely criticised and the Government has been strongly urged to 'bring back Matron' in the latest report from the Health Ombudsman Select Committee. PMID- 27667600 TI - Mortality rates. AB - Death rates for boys and girls aged 5-9 fell by 48 per cent between 1971 and 1988, and by 30 per cent for boys and 38 percent for girls aged 10-14 according to the Office of Population Censuses and Surveys. Over the same period stillbirth and neonatal death rates decreased by over 55 per cent, and postnatal by almost one third. PMID- 27667602 TI - ? AB - Healthy outlook: Sisters Sue Hardy and Shelagh Vidler are pictured after the unveiling of a plaque in Old Park Wood next to Harefield Hospital. The plaque commemorates a L40,000 donation from the National Grid Company to the RSNC Wildlife Trusts Partnership, L3.000 of which will help glade-clearance work in the wood, which is used by staff and patients at the hospital. PMID- 27667601 TI - Campaign will promote 'partnerships in care'. AB - A unique new breast-care campaign aimed at educating women and health care workers was launched last week with all-party Commons support. PMID- 27667604 TI - Guidelines for reducing claims. AB - A firm of solicitors that specialise inlitigation claims in health care is planning to produce guidelines to reduce negligence claims for obstetrics and back injury cases among nurses. PMID- 27667606 TI - Autumn launch for new television scheme. AB - An innovative education scheme for nurses is to be launched this autumn by the BBC, the Royal College of Nursing, Nursing Standard and Healthcare Productions Ltd. PMID- 27667605 TI - Ashworth staff urged to give evidence. AB - Present and former staff at Ashworth Special Hospital in Liverpool have been urged to come forward with evidence to a new inquiry into allegations of ill treatment of patients there. PMID- 27667607 TI - Autumn review could lead to more academic weight. AB - Nurses' qualifications could carry more academic weight following a major review of the credit accumulation scheme to be carried out in the autumn. PMID- 27667608 TI - RCN to carry out survey of members' experiences. AB - The Royal College of Nursing is to carry out a survey of members' experiences of, and need for knowledge in the area of child protection. PMID- 27667610 TI - Parliament. AB - Heart attacks are increasing among women more than twice as fast as among men. Over the past seven years the total number of heart attacks in England went up by just under 11 per cent, health minister Viriginia Bottomley told the Commons. PMID- 27667614 TI - Hepatitis C virus is sexually transmitted. AB - Evidence that the hepatitis C virus is sexually transmitted has been shown by researchers at University College and Middlesex School of Medicine. PMID- 27667612 TI - World news. AB - Mexico Prostitutes in Mexico City have been recruited in a Government campaign to prevent the heterosexual spread of HIV and are urging their clients to use condoms and practise safer sex. PMID- 27667615 TI - ? AB - Urine testing: A new one-step test for human chorionic gonadotrophin hormone can detect ectopic pregnancies, according to the latest research. PMID- 27667616 TI - One-step urine tests for ectopic pregnancy. AB - Routine rapid one-step urine tests for human chorionic gonadotrophin hormone have been shown to be highly effective in detecting ectopic pregnancies, new research in Scotland has found. PMID- 27667617 TI - Nurse-run asthma clinic benefits GPS. AB - Setting up a nurse-run asthma clinic in general practice leads to a substantial reduction in GP consultations, days off school or work and patients' requirements for oral steroids, according to a new report. PMID- 27667618 TI - Child health records should be parent held. AB - Child health records have a better chance of being completed by health professionals if they are kept by parents, research shows. PMID- 27667619 TI - Hepatitis and liver cancer link found. AB - Scientists say they now have 'overwhelming' evidence for the direct involvement of hepatitis B virus in the development of liver cancer. PMID- 27667620 TI - Venesection for epo- induced hypertension. AB - Venesection is suggested as a method for correcting the life-threatening malignant hypertension sometimes associated with the use of erythropoietin. PMID- 27667622 TI - Metabolic disorder and child abuse. AB - There is little likelihood that child abuse and metabolic bone disease are confused in cases which reach the stage of court proceedings. PMID- 27667621 TI - More evidence on prone position and SIDS. AB - The association between prone position and sudden infant death syndrome has been strengthened by research. PMID- 27667623 TI - Haemodialysis and helplessness. AB - Patients receiving haemodialysis might experience more feelings of helplessness than their counterparts on continuous ambulatory peritoneal dialysis (CAPD). PMID- 27667624 TI - Consulting on health. AB - The Green Paper announced in the House of Commons last week includes ambitious targets to reduce the number of deaths from preventable diseases and promote good health, bringing England into line with the World Health Organization's target of 'Health for All by the year 2000'. It is open for consultation until October, when a White Paper will be drawn up. PMID- 27667625 TI - Why women have to be special. AB - Alex Mathieson's report on the Empowering Women seminar held at RCN Congress ('Success in a man's world', Nursing Standard May 29), reminded me this event was without doubt the high-spot of my week. PMID- 27667626 TI - Abortion and nurses who say no. AB - It is a pity that Health Secretary William Waldegrave does not feel able to take any action to make it easier for nurses to avoid taking part in abortions (Nursing Standard News, May22). PMID- 27667627 TI - Nurses are not professionals. AB - Why does the author of 'No, non, niet, nein, no ...' (Nursing Standard May 1) argue that nursing auxiliaries are not professionals? We, the trained staff, are not professionals. PMID- 27667629 TI - Information exchange. AB - The National Association for the Welfare of Children in Hospital is conducting a study into the problems parents or carers face when visiting children in hospital. PMID- 27667628 TI - Correcting the heads and tales. AB - I must correct a misunderstanding in the news article 'Ashworth intimidation shocks Congress' (Nursing Standard May 29). PMID- 27667631 TI - ? PMID- 27667632 TI - ABC of AIDS Adler M W , editor ABC of AIDS 2nd edition British Medical Journal 72pp L10.95 0-7279-0267-7 [Formula: see text]. AB - The ABC of AIDS is aimed specifically at the medical profession, both hospital and community. The second edition is an updated version of the original, a collection of articles from the BMA. PMID- 27667630 TI - Vote of thanks from forum. AB - On behalf of the mental handicap nurses who attended this year's Royal College of Nursing Congress in Harrogate, I should like to acknowledge the excellent work done throughout the week by the Agenda Committee. PMID- 27667633 TI - The Mentally Disordered Offender K Herbst and J Gunn , editors The mentally discovered offender Butterworth-Heinemann 258pp L35 0-7506-0028-4 [Formula: see text]. AB - Separating the 'mad' from the 'bad' has proved a complex dilemma for the British penal system throughout its history. In recent times, the 1975 Butler Report made a number of recommendations for improving the lot of the mentally ill offender; though, as The Mentally Disordered Offender illustrates, the problem remains as intricate and profound as ever before. PMID- 27667635 TI - Gossip. PMID- 27667634 TI - Bibliography of Nursing Quality Assurance and Standards of Care 1932-1987 A Kitson and Bibliography of Nursing Quality Assurance and Standards of Care 1932 1987 G Harvey Scutari Press 290pp L24.95 1-871364-46-9 [Formula: see text]. AB - The purpose of the RCN Nursing Quality Assurance bibliography is to provide a record of the documented developments that have happened between 1932 and 1987 within nursing quality assurance. The bibliography contains 480 articles, each classified into four main sections derived from the literature. Each article is coded according to section, subsection, author and date of publication. The bulk of the text offers summaries of the articles in each section and is followed by excellent indexes. PMID- 27667636 TI - Listings. PMID- 27667637 TI - High-speed microscopy of continuously moving cell culture vessels. AB - We report a method of high-speed phase contrast and bright field microscopy which permits large cell culture vessels to be scanned at much higher speed (up to 30 times faster) than when conventional methods are used without compromising image quality. The object under investigation moves continuously and is captured using a flash illumination which creates an exposure time short enough to prevent motion blur. During the scan the object always stays in focus due to a novel hardware-autofocus system. PMID- 27667638 TI - Highly-stretchable 3D-architected Mechanical Metamaterials. AB - Soft materials featuring both 3D free-form architectures and high stretchability are highly desirable for a number of engineering applications ranging from cushion modulators, soft robots to stretchable electronics; however, both the manufacturing and fundamental mechanics are largely elusive. Here, we overcome the manufacturing difficulties and report a class of mechanical metamaterials that not only features 3D free-form lattice architectures but also poses ultrahigh reversible stretchability (strain > 414%), 4 times higher than that of the existing counterparts with the similar complexity of 3D architectures. The microarchitected metamaterials, made of highly stretchable elastomers, are realized through an additive manufacturing technique, projection microstereolithography, and its postprocessing. With the fabricated metamaterials, we reveal their exotic mechanical behaviors: Under large-strain tension, their moduli follow a linear scaling relationship with their densities regardless of architecture types, in sharp contrast to the architecture-dependent modulus power-law of the existing engineering materials; under large-strain compression, they present tunable negative-stiffness that enables ultrahigh energy absorption efficiencies. To harness their extraordinary stretchability and microstructures, we demonstrate that the metamaterials open a number of application avenues in lightweight and flexible structure connectors, ultraefficient dampers, 3D meshed rehabilitation structures and stretchable electronics with designed 3D anisotropic conductivity. PMID- 27667639 TI - Illness, normality and identity: the experience of heart transplant as a young adult. AB - PURPOSE: End stage heart failure and transplant present great opportunities and challenges for patients of all ages. However, young adulthood may present additional specific challenges associated with the development of identity, career and romantic relationships. Despite recognition of greater mortality rates in young adults, consideration of the experience of transplant during this life stage has been largely overlooked in the literature. The aim of this study was to explore the experience of heart transplant in young adults. METHOD: Interviews were conducted with nine participants across three transplant services in the United Kingdom and the data subject to interpretative phenomenological analysis. RESULTS: Analysis identified three themes. "Separating from illness" and "working toward normality" involved limiting the influence of illness on identity, as well as reengaging with typical functioning in young adulthood. "Integrating transplant into identity" involved acknowledging the influence of living with a shortened life expectancy. CONCLUSIONS: The need for support that recognizes specific challenges of transplant as a young adult is discussed (e.g. the development of age specific end of life pathways, improved communication between transplant recipients, their families and teams), including consideration of the impact of societal discourses (e.g. gift of life) which provided additional challenges for patients. IMPLICATIONS FOR REHABILITATION Heart transplant presents specific challenges according to the recipient's life stage. The needs of young adult recipients should be considered. Transplant professionals should consider providing opportunities for peer support and addressing the identities and values of young adult transplant recipients during rehabilitation. PMID- 27667641 TI - Machine learning-, rule- and pharmacophore-based classification on the inhibition of P-glycoprotein and NorA. AB - The efflux pumps P-glycoprotein (P-gp) in humans and NorA in Staphylococcus aureus are of great interest for medicinal chemists because of their important roles in multidrug resistance (MDR). The high polyspecificity as well as the unavailability of high-resolution X-ray crystal structures of these transmembrane proteins lead us to combining ligand-based approaches, which in the case of this study were machine learning, perceptual mapping and pharmacophore modelling. For P-gp inhibitory activity, individual models were developed using different machine learning algorithms and subsequently combined into an ensemble model which showed a good discrimination between inhibitors and noninhibitors (acctrain diverse = 84%; accinternal-test = 92% and accexternal-test = 100%). For ligand promiscuity between P-gp and NorA, perceptual maps and pharmacophore models were generated for the detection of rules and features. Based on these in silico tools, hit compounds for reversing MDR were discovered from the in-house and DrugBank databases through virtual screening in an attempt to restore drug sensitivity in cancer cells and bacteria. PMID- 27667640 TI - Ultra-stable clock laser system development towards space applications. AB - The increasing performance of optical lattice clocks has made them attractive for scientific applications in space and thus has pushed the development of their components including the interrogation lasers of the clock transitions towards being suitable for space, which amongst others requires making them more power efficient, radiation hardened, smaller, lighter as well as more mechanically stable. Here we present the development towards a space-compatible interrogation laser system for a strontium lattice clock constructed within the Space Optical Clock (SOC2) project where we have concentrated on mechanical rigidity and size. The laser reaches a fractional frequency instability of 7.9 * 10-16 at 300 ms averaging time. The laser system uses a single extended cavity diode laser that gives enough power for interrogating the atoms, frequency comparison by a frequency comb and diagnostics. It includes fibre link stabilisation to the atomic package and to the comb. The optics module containing the laser has dimensions 60 * 45 * 8 cm3; and the ultra-stable reference cavity used for frequency stabilisation with its vacuum system takes 30 * 30 * 30 cm3. The acceleration sensitivities in three orthogonal directions of the cavity are 3.6 * 10-10/g, 5.8 * 10-10/g and 3.1 * 10-10/g, where g ~ 9.8 m/s2 is the standard gravitational acceleration. PMID- 27667642 TI - Description of Jeotgalibacillus alkaliphilus sp. nov., isolated from a solar salt pan, and Jeotgalibacillus terrae sp. nov., a name to replace 'Jeotgalibacillus soli' Chen et al. 2010. AB - A Gram-stain-positive, non-motile, rod-shaped bacterium (strain JC303T) isolated from a salt pan was identified based on 16S rRNA gene sequence analysis as a member of the genus Jeotgalibacillus. It was related most closely to Jeotgalibacillus salarius ASL-1T (99.1 % similarity), Jeotgalibacillusalimentarius YKJ-13T (97.9 %), Jeotgalibacillussoli JSM 081008 (97.9 %), Jeotgalibacillusmalaysiensis D5T (97.8 %), Jeotgalibacillusmarinus DSM 1297T (96.3 %), Jeotgalibacilluscampisalis SF-57T (96.1 %) and J. soli P9T (94.9 %). Genomic relatedness based on DNA-DNA hybridization of strain JC303T with the type strains of the closest related species was less than 40 %. Diphosphatidylglycerol, three aminophospholipids, an unidentified aminoglycolipid, two unidentified phospholipids and an unidentified lipid were the polar lipids of strain JC303T. Major (>10 %) fatty acids were anteiso-C15 : 0, iso-C15 : 0 and iso-C14 : 0. Cell-wall amino acids contained peptidoglycan with l-lysine as the diagnostic diamino acid. Strain JC303T contained MK-7 as the predominant (96 %) menaquinone with the presence of a significant amount (4 %) of MK-8. The DNA G+C content was 43 mol%. On the basis of morphological, physiological, genotypic, phylogenetic and chemotaxonomic analyses, strain JC303T is considered to represent a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus alkaliphilus sp. nov. is proposed. The type strain is JC303T (=KCTC 33662T=LMG 28756T). In addition, we propose to rename J. soli (Chen et al., 2010), an illegitimate homonym of the validly published name Jeotgalibacillus soli(Cunha et al., 2012) as Jeotgalibacillus terrae sp. nov. with type strain JSM 081008T (=DSM 22174T=KCTC 13528T). PMID- 27667645 TI - In Situ Ratiometric Quantitative Tracing of Intracellular Leucine Aminopeptidase Activity via an Activatable Near-Infrared Fluorescent Probe. AB - Leucine aminopeptidase (LAP), one of the important proteolytic enzymes, is intertwined with the progress of many pathological disorders as a well-defined biomarker. To explore fluorescent aminopeptidase probe for quantitative detection of LAP distribution and dynamic changes, herein we report a LAP-targeting near infrared (NIR) fluorescent probe (DCM-Leu) for ratiometric quantitative trapping of LAP activity in different kinds of living cells. DCM-Leu is composed of a NIR emitting fluorophore (DCM) as a reporter and l-leucine as a triggered moiety, which are linked together by an amide bond specific for LAP cleavage. High contrast on the ratiometric NIR fluorescence signal can be achieved in response to LAP activity, thus enabling quantification of endogenous LAP with "build-in calibration" as well as minimal background interference. Its ratiometric NIR signal can be blocked in a dose-dependent manner by bestatin, an LAP inhibitor, indicating that the alteration of endogenous LAP activity results in these obviously fluorescent signal responses. It is worth noting that DCM-Leu features striking characteristics such as a large Stokes shift (~205 nm), superior selectivity, and strong photostability responding to LAP. Impressively, not only did we successfully exemplify DCM-Leu in situ ratiometric trapping and quantification of endogenous LAP activity in various types of living cells, but also, with the aid of three-dimensional confocal imaging, the intracellular LAP distribution is clearly observed from different perspectives for the first time, owing to the high signal-to-noise of ratiometric NIR fluorescent response. Collectively, these results demonstrate preclinical potential value of DCM-Leu serving as a useful NIR fluorescent probe for early detection of LAP-associated disease and screening inhibitor. PMID- 27667644 TI - Level of agreement between cardiac output measurements using Nexfin(r) and thermodilution in morbidly obese patients undergoing laparoscopic surgery. AB - Morbidly obese patients are at increased risk of intra-operative haemodynamic instability, which may necessitate intensive monitoring. Non-invasive monitoring is increasingly used to measure cardiac output; however, it is unknown whether the weight-based algorithm utilised in these devices is applicable to patients with morbid obesity. We compared the level of agreement and trending ability of non-invasive cardiac output measurements (Nexfin(r) ) with the gold-standard thermodilution technique in 30 morbidly obese patients undergoing laparoscopic surgery. Bland-Altman analysis revealed a mean (SD) bias of 0.60 (1.62) l.min-1 (limits of agreement -2.67 to 3.86 l.min-1 ) and the precision error was 46%. Polar plot analysis resulted in an angular bias of 2.61 degrees , radial limits of agreement of -60.08 degrees to 49.82 degrees and angular concordance rate was 77%. Both agreement and trending were outside the Critchley criteria for the comparison of cardiac output devices with a gold-standard. Nexfin has an unacceptable level of agreement compared with thermodilution for cardiac output measurement in morbidly obese patients. PMID- 27667646 TI - lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer. AB - Esophageal cancer (EC) is one of the most common gastrointestinal cancers, which leads to the sixth ranking of cancer-related death. Long non-coding RNAs (lncRNAs) play pivotal roles in many biological processes. lncRNA human urothelial carcinoma associated 1 (UCA1) is significantly upregulated and functions as an important oncogene in many types of human cancers. However, the role of UCA1 in EC and its underlying mechanism remains unclear. In the present study, we demonstrated that UCA1 was significantly upregulated in EC tissues and associated with poor prognosis. Overexpression of UCA1 promoted the proliferation of EC cells, while silence of UCA1 inhibited EC cells growth. Furthermore, we found that Sox4 was a direct target gene of UCA1. UCA1 regulated Sox4 expression through functioning as a competing endogenous RNA (ceRNA). UCA1 directly interacted with miR-204 and decreased the binding of miR-204 to Sox4 3'UTR, which suppressed the degradation of Sox4 mRNA by miR-204. This study provides the first evidence that UCA1 promotes cell proliferation through Sox4 in EC, suggesting that UCA1 and Sox4 may be potential therapeutic targets for EC. PMID- 27667647 TI - Comparison of the costs of active surveillance and immediate surgery in the management of low-risk papillary microcarcinoma of the thyroid. AB - The incidence of thyroid cancer is increasing rapidly in many countries, resulting in rising societal costs of the care of thyroid cancer. We reported that the active surveillance of low-risk papillary microcarcinoma had less unfavorable events than immediate surgery, while the oncological outcomes of these managements were similarly excellent. Here we calculated the medical costs of these two managements. We created a model of the flow of these managements, based on our previous study. The flow and costs include the step of diagnosis, surgery, prescription of medicine, recurrence, salvage surgery for recurrence, and care for 10 years after the diagnosis. The costs were calculated according to the typical clinical practices at Kuma Hospital performed under the Japanese Health Care Insurance System. If conversion surgeries were not considered, the 'simple cost' of active surveillance for 10 years was 167,780 yen/patient. If there were no recurrences, the 'simple cost' of immediate surgery was calculated as 794,770 yen/patient to 1,086,070 yen/patient, depending on the type of surgery and postoperative medication. The 'simple cost' of surgery was 4.7 to 6.5 times the 'simple cost' of surveillance. When conversion surgeries and recurrence were considered, the 'total cost' of active surveillance for 10 years became 225,695 yen/patient. When recurrence were considered, the 'total cost' of immediate surgery was 928,094 yen/patient, which was 4.1 times the 'total cost' of the active surveillance. At Kuma Hospital in Japan, the 10-year total cost of immediate surgery was 4.1 times expensive than active surveillance. PMID- 27667648 TI - Multiple heart-cutting two dimensional liquid chromatography mass spectrometry: Towards real time determination of related impurities of bio-pharmaceuticals in salt based separation methods. AB - Many of the chromatographic methods used in industry to determine related impurities in bio pharmaceuticals employ salt containing mobile phases. "Salty" mobile phases often provide superior chromatographic performance but are not compatible with mass spectrometry (MS) detection. Peak tracking necessary for method development is therefore often based on peak areas and the chemist's experience/intuition. In addition, MS characterization of impurities usually is done by offline fraction collection, which apart from being time consuming often suffers from poor recovery or the degradation of impurities collected. The recent development of multiple heart-cutting (MHC) two-dimensional liquid chromatography (2D-LC) provides a way to address these problems. This study shows how MHC 2D-LC MS can be used to obtain almost real time MS data for bovine insulin related impurities present at low level (<<0.03%). High quality MS spectra were obtained even for a first dimension using a mobile phase containing high concentrations of sodium, sulphate and phosphate. Thereby MHC 2D-LC-MS offers a possibility to eliminate the guesswork currently associated with peak tracking during method development. Furthermore, in contrast to current characterization methods involving fraction collection, solvent reduction/exchange etc., MS determination is done directly, which markedly shortens the workflow (from days to hours) and reduces the risk for poor recovery and degradation. PMID- 27667649 TI - Nonhydrolytic sol-gel approach to facile creation of surface-bonded zirconia organic-inorganic hybrid coatings for sample preparation. Iota. Capillary microextraction of catecholamine neurotransmitters. AB - Nonhydrolytic sol-gel (NHSG) route was used for the creation of novel zirconia polypropylene oxide (ZrO2-PPO) sol-gel hybrid sorbents in the form of surface coatings for the extraction and preconcentration of catecholamine neurotransmitters and molecules structurally related to their deaminated metabolites. In comparison to other sorbents made of inorganic transition metal oxides, the presented hybrid organic-inorganic sorbents facilitated reversible sorption properties that allowed for efficient desorption of the extracted analytes by LC-MS compatible mobile phases. The presented sol-gel hybrid sorbents effectively overcame the major drawbacks of traditional silica- or polymer-based sorbents by providing superior pH stability (pH range: 0-14), and a variety of intermolecular interactions. Nonaqueous sol-gel treatment of PPO with ZrCl4 was employed for the derivatization of the terminal hydroxyl groups on PPO, providing zirconium trichloride-containing end groups characterized by enhanced sol-gel reactivity. NHSG ZrO2-PPO sorbent provided excellent microextraction performance for catecholamines, low detection limits (5.6-9.6pM), high run-to-run reproducibility (RSD 0.6-5.1%), high desorption efficiency (95.0-99.5%) and high enrichment factors (~1480-2650) for dopamine and epinephrine, respectively, extracted from synthetic urine samples. The presented sol-gel sorbents provided effective alternative to conventional extraction media providing unique physicochemical characteristics and excellent extraction capability. PMID- 27667650 TI - Hydrothermally grown and self-assembled modified titanium and nickel oxide composite nanosheets on Nitinol-based fibers for efficient solid phase microextraction. AB - A novel titanium and nickel oxide composite nanosheets (TiO2/NiOCNSs) coating was in situ grown on a Nitinol (NiTi) wire by direct hydrothermal treatment and modified by self-assembly of trichlorophenylsilane for solid phase microextraction (SPME). TiO2/NiOCNSs were radially oriented and chemically bonded to the NiTi substrate with double-faced open access sites. Moreover the phenyl modified TiO2/NiOCNSs (TiO2/NiOCNSs-Ph) coating exhibited original surface supporting framework favorable for effective SPME. The extraction performance of TiO2/NiOCNSs-Ph coated NiTi (NiTi-TiO2/NiOCNSs-Ph) fiber was investigated for the concentration and detection of ultraviolet (UV) filters, polycyclic aromatic hydrocarbons (PAHs), phthalate acid esters and polychlorinated biphenyls coupled to HPLC with UV detection. The novel fiber exhibited better selectivity for UV filters and PAHs and presented greater extraction capability compared to commercial polydimethylsiloxane and polyacrylate fibers. Under the optimized conditions for SPME of UV filters, the proposed method presented linear ranges from 0.1 to 300MUg/L with correlation coefficients of higher than 0.999 and limits of detection from 0.030MUg/L to 0.064MUg/L. Relative standard deviations (RSDs) were below 7.16% and 8.42% for intra-day and inter-day measurements with the single fiber, respectively. Furthermore RSDs for fiber-to-fiber reproducibility from 6.57% to 8.93% were achieved. The NiTi-TiO2/NiOCNSs-Ph fiber can be used up to 200 times. The proposed method was successfully applied to the preconcentration and determination of trace target UV filters in different environmental water samples. The relative recoveries from 87.3% to 104% were obtained with RSDs less than 8.7%. PMID- 27667651 TI - Development of methods for using workers' compensation data for surveillance and prevention of occupational injuries among State-insured private employers in Ohio. AB - BACKGROUND: Workers' compensation (WC) claims data may be useful for identifying high-risk industries and developing prevention strategies. METHODS: WC claims data from private-industry employers insured by the Ohio state-based workers' compensation carrier from 2001 to 2011 were linked with the state's unemployment insurance (UI) data on the employer's industry and number of employees. National Labor Productivity and Costs survey data were used to adjust UI data and estimate full-time equivalents (FTE). Rates of WC claims per 100 FTE were computed and Poisson regression was used to evaluate differences in rates. RESULTS: Most industries showed substantial claim count and rate reductions from 2001 to 2008, followed by a leveling or slight increase in claim count and rate from 2009 to 2011. Despite reductions, there were industry groups that had consistently higher rates. CONCLUSION: WC claims data linked to employment data could be used to prioritize industries for injury research and prevention activities among State insured private employers. Am. J. Ind. Med. 59:1087-1104, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27667653 TI - The Spanish long-term care system in transition: Ten years since the 2006 Dependency Act. AB - At the end of 2006, a new System for Promotion of Personal Autonomy and Assistance for Persons in a Situation of Dependency (SAAD) was established in Spain through the approval of the Act 39/2006 of 14th December (the Dependency Act, DA). The DA acknowledged the universal entitlement of Spanish citizens to social services. The recent economic crisis added degrees of uncertainty to several dimensions of the SAAD implementation process. Firstly, the political consensus on which its foundation rested upon has weakened. Secondly, implementation of the SAAD was hampered by several challenges that emerged in the context of the economic crisis. Thirdly, the so-called "dependency limbo" (i.e. the existence of a large number of people eligible for benefits but who do not receive them) has become a structural feature of the system. Finally, contrary to the spirit of the DA, monetary benefits have become the norm rather than a last resort. High heterogeneity across regions regarding the number of beneficiaries covered and services provided reveal the existence of regional inequity in access to long-term care services in the country. Broadly, the current evidence on the state of the SAAD suggests the need to improve the quality of governance, to enhance coordination between health and social systems, to increase the system's transparency, to foster citizens' participation in decision-making and to implement a systematic monitoring of the system. PMID- 27667652 TI - Evaluation of Body Weight, Body Condition, and Muscle Condition in Cats with Hyperthyroidism. AB - BACKGROUND: The contribution of fat loss versus muscle wasting to the loss of body weight seen in hyperthyroid cats is unknown. OBJECTIVES: To investigate body weight, body condition score (BCS), and muscle condition score (MCS) in hyperthyroid cats. ANIMALS: Four hundred sixty-two cats with untreated hyperthyroidism, 117 of which were reevaluated after treatment. METHODS: Prospective cross-sectional and before-after studies. Untreated hyperthyroid cats had body composition evaluated (body weight, BCS, and MCS). A subset of these cats were reevaluated 3-12 months after treatment when euthyroid. RESULTS: Pretreatment body weight (median, 4.36 kg; IQR, 3.5 to 5.2 kg) was lower than premorbid weight (5.45 kg; IQR, 4.6 to 6.4 kg, P < .0001) recorded 1-2 years before diagnosis. 154 (35.3%) cats were thin or emaciated; 357 (77.3%) had loss of muscle mass. Cats showed increases in body weight (median, 4.1 kg to 5.0 kg), BCS (median, 3/5 to 3.5/5), and MCS (2/3 to 3/3) after treatment (P < .001), but mild-to-moderate muscle wasting persisted in 45% of treated cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Most hyperthyroid cats lose body weight but maintain an ideal or overweight BCS, with only a third being underweight. As in human hyperthyroid patients, this weight loss is associated with muscle wasting, which affects >75% of hyperthyroid cats. Successful treatment leads to weight gain and increase of BCS in most cats, but almost half fail to regain normal muscle mass. PMID- 27667654 TI - Long and irregular menstrual cycles, polycystic ovary syndrome, and ovarian cancer risk in a population-based case-control study. AB - Long and irregular menstrual cycles, a hallmark of polycystic ovary syndrome (PCOS), have been associated with higher androgen and lower sex hormone binding globulin levels and this altered hormonal environment may increase the risk of specific histologic subtypes of ovarian cancer. We investigated whether menstrual cycle characteristics and self-reported PCOS were associated with ovarian cancer risk among 2,041 women with epithelial ovarian cancer and 2,100 controls in the New England Case-Control Study (1992-2008). Menstrual cycle irregularity, menstrual cycle length, and PCOS were collected through in-person interview. Unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for ovarian cancer risk overall, and polytomous logistic regression to evaluate whether risk differed between histologic subtypes. Overall, we observed no elevation in ovarian cancer risk for women who reported periods that were never regular or for those reporting a menstrual cycle length of >35 days with ORs of 0.87 (95% CI = 0.69-1.10) and 0.83 (95% CI = 0.44-1.54), respectively. We observed no overall association between self-reported PCOS and ovarian cancer (OR = 0.97; 95% CI = 0.61-1.56). However, we observed significant differences in the association with menstrual cycle irregularity and risk of ovarian cancer subtypes (pheterogeneity = 0.03) as well as by BMI and OC use (pinteraction < 0.01). Most notable, menstrual cycle irregularity was associated with a decreased risk of high grade serous tumors but an increased risk of serous borderline tumors among women who had never used OCs and those who were overweight. Future research in a large collaborative consortium may help clarify these associations. PMID- 27667657 TI - Lichen myxedematosus: diagnostic criteria, classification, and severity grading. AB - BACKGROUND: Lichen myxedematosus (LM) is a rare, chronic idiopathic disorder characterized clinically by waxy, closely set papules and histopathologically by diffuse dermal mucin deposition and fibroblast proliferation. The most recent classification of LM was proposed in 2001; however, it seems to be complex, confusing, and imprecise. Herein, we present seven cases of LM to evaluate the validity of the current classification, to propose new diagnostic criteria and classification, and to suggest a clinically relevant severity grading system for this rare disorder. MATERIALS AND METHODS: The study included seven patients with different presentations and severities of LM. All patients were subjected to thorough dermatological and systemic examination, routine laboratory tests, evaluation of thyroid function, protein electrophoresis, and detailed investigations to detect systemic involvement. RESULTS: The current classification does not meet the requirements of proper diagnosis of different presentations of LM. Subtyping of the studied patients differs greatly according to the old classification and the newly proposed one. New diagnostic criteria, classification, and grading are consequently suggested. CONCLUSIONS: We propose two sets of diagnostic criteria to define the disease more precisely and to avoid confusion associated with the other classification. The first set comprises constant clinical and histopathological features that are always present in every case, and the second set includes associated features that were variably reported in some patients. LM is then subclassified according to the presence or absence of systemic manifestations into a systemic severe form (scleromyxedema) and a non disabling, pure cutaneous form. PMID- 27667655 TI - Quantification and biodistribution of iron oxide nanoparticles in the primary clearance organs of mice using T1 contrast for heating. AB - PURPOSE: To use contrast based on longitudinal relaxation times (T1 ) or rates (R1 ) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs. METHODS: Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 naive mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues. RESULTS: Signal enhancement from positive T1 contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R1 and volumetric SAR in hyperthermia therapy was observed. CONCLUSION: The linear dependence between R1 and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702-712, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27667658 TI - Estimating the Basic Reproductive Number for African Swine Fever Using the Ukrainian Historical Epidemic of 1977. AB - In 1977, Ukraine experienced a local epidemic of African swine fever (ASF) in the Odessa region. A total of 20 settlements were affected during the course of the epidemic, including both large farms and backyard households. Thanks to timely interventions, the virus circulation was successfully eradicated within 6 months, leading to no additional outbreaks. Detailed report of the outbreak's investigation has been publically available from 2014. The report contains some quantitative data that allow studying the ASF-spread dynamics in the course of the epidemic. In our study, we used this historical epidemic to estimate the basic reproductive number of the ASF virus both within and between farms. The basic reproductive number (R0 ) represents the average number of secondary infections caused by one infectious unit during its infectious period in a susceptible population. Calculations were made under assumption of an exponential initial growth by fitting the approximating curve to the initial segments of the epidemic curves. The R0 both within farm and between farms was estimated at 7.46 (95% confidence interval: 5.68-9.21) and 1.65 (1.42-1.88), respectively. Corresponding daily transmission rates were estimated at 1.07 (0.81-1.32) and 0.09 (0.07-0.10). These estimations based on historical data are consistent with those using data generated by the recent epidemic currently affecting eastern Europe. Such results contribute to the published knowledge on the ASF transmission dynamics under natural conditions and could be used to model and predict the spread of ASF in affected and non-affected regions and to evaluate the effectiveness of different control measures. PMID- 27667656 TI - Global patterns of workplace productivity for people with depression: absenteeism and presenteeism costs across eight diverse countries. AB - PURPOSE: Depression is a leading cause of disability worldwide. Research suggests that by far, the greatest contributor to the overall economic impact of depression is loss in productivity; however, there is very little research on the costs of depression outside of Western high-income countries. Thus, this study examines the impact of depression on workplace productivity across eight diverse countries. METHODS: We estimated the extent and costs of depression-related absenteeism and presenteeism in the workplace across eight countries: Brazil, Canada, China, Japan, South Korea, Mexico, South Africa, and the USA. We also examined the individual, workplace, and societal factors associated with lower productivity. RESULTS: To the best of our knowledge, this is the first study to examine the impact of depression on workplace productivity across a diverse set of countries, in terms of both culture and GDP. Mean annual per person costs for absenteeism were lowest in South Korea at $181 and highest in Japan ($2674). Mean presenteeism costs per person were highest in the USA ($5524) and Brazil ($5788). Costs associated with presenteeism tended to be 5-10 times higher than those associated with absenteeism. CONCLUSIONS: These findings suggest that the impact of depression in the workplace is considerable across all countries, both in absolute monetary terms and in relation to proportion of country GDP. Overall, depression is an issue deserving much greater attention, regardless of a country's economic development, national income or culture. PMID- 27667660 TI - Prenucleation Self-Assembly and Chiral Discrimination Mechanisms during Solution Crystallisation of Racemic Diprophylline. AB - The crystallisation behaviour of (RS)-diprophylline (DPL) in two different solvents is investigated to assess the incidence of solvated pre-associations on nucleation, crystal growth and chiral discrimination. In the solvated state, Raman spectroscopy shows that dimeric associations similar to those depicted in the crystalline solid solution (ssRII) predominate in isopropanol (IPA), which may account for the systematic spontaneous nucleation of this crystal form from this solvent. By contrast, spontaneous nucleation in DMF yields the stable racemic compound RI, consistently with the distinct features of the Raman spectrum collected in this solvent. A crystal growth study of ssRII in IPA reveals that the crystal habitus is impacted by the solution enantiomeric excess; this is explained by increased competition between homo- and heterochiral pre associations. This is supported by a molecular modelling study on the enantiomeric selectivity of the DPL crystal lattices. The combination of assessment methods on solution chemistry, nucleation and chiral discrimination provides methodological tools from which the occurrence of solid solutions can be rationalised. PMID- 27667661 TI - Identification and sequence analysis of a novel HLA-A*33 allele, HLA-A*33:88. AB - HLA-A*33:88 differs from HLA-A*33:03:01 by one nucleotide exchange at position 475, G>A (codon 135 GCG>ACG). PMID- 27667659 TI - Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily. AB - BACKGROUND AND PURPOSE: Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. EXPERIMENTAL APPROACH: The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg.kg-1 base weight) from saline. One group received additional nicotine treatment post-session (1.78 mg.kg-1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). KEY RESULTS: Daily repeated nicotine treatment produced a time-related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro-beta-erythroidine did not. Midazolam produced 0% nicotine-lever responding. The nAChR agonists epibatidine, RTI-36, cytisine and varenicline produced >96% nicotine-lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine-like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. CONCLUSION AND IMPLICATIONS: Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID- 27667662 TI - Antibodies to major histocompatibility complex class II antigens directly prime neutrophils and cause acute lung injury in a two-event in vivo rat model. AB - BACKGROUND: Transfusion-related acute lung injury (TRALI) is a significant cause of mortality, especially after transfusions containing antibodies to major histocompatibility complex (MHC) class II antigens. We hypothesize that a first event induces both 1) polymorphonuclear neutrophils (PMNs) to express MHC class II antigens, and 2) activation of the pulmonary endothelium, leading to PMN sequestration, so that the infusion of specific MHC class II antibodies to these antigens causes PMN-mediated acute lung injury (ALI). STUDY DESIGN AND METHODS: Rats were treated with saline (NS), endotoxin (lipopolysaccharide [LPS]), or cytokines (interferon-gamma [IFNgamma], macrophage colony-stimulating factor [MCSF], tumor necrosis factor-alpha [TNFalpha]); the PMNs were isolated; and the surface expression of the MHC class II antigen OX6 and priming by OX6 antibodies were measured by flow cytometry or priming assays. RESULTS: A two-event model of ALI was completed with NS, LPS, or IFNgamma/MCSF/TNFalpha (first events) and the infusion of OX6 (second event). Compared with NS incubation, rats treated with either LPS or IFNgamma/MCSF/TNFalpha exhibited OX6 PMN surface expression, OX6 antibodies primed the formyl-methionyl-leucyl phenylalanine (fMLF)-activated respiratory burst, and PMN sequestration was increased. OX6 antibody infusion into LPS-incubated or IFNgamma/MCSF/TNFalpha-incubated rats elicited ALI, the OX6 antibody was present on the PMNs, and PMN depletion abrogated ALI. CONCLUSION: Proinflammatory first events induce PMN MHC class II surface expression, activation of the pulmonary endothelium, and PMN sequestration such that the infusion of cognate antibodies precipitates TRALI. PMID- 27667663 TI - A study of wrist-worn activity measurement as a potential real-world biomarker for late-life depression. AB - BACKGROUND: Late-life depression (LLD) is associated with a decline in physical activity. Typically this is assessed by self-report questionnaires and, more recently, with actigraphy. We sought to explore the utility of a bespoke activity monitor to characterize activity profiles in LLD more precisely. METHOD: The activity monitor was worn for 7 days by 29 adults with LLD and 30 healthy controls. Subjects underwent neuropsychological assessment and quality of life (QoL) (36-item Short-Form Health Survey) and activities of daily living (ADL) scales (Instrumental Activities of Daily Living Scale) were administered. RESULTS: Physical activity was significantly reduced in LLD compared with controls (t = 3.63, p < 0.001), primarily in the morning. LLD subjects showed slower fine motor movements (t = 3.49, p < 0.001). In LLD patients, activity reductions were related to reduced ADL (r = 0.61, p < 0.001), lower QoL (r = 0.65, p < 0.001), associative learning (r = 0.40, p = 0.036), and higher Montgomery-Asberg Depression Rating Scale score (r = -0.37, p < 0.05). CONCLUSIONS: Patients with LLD had a significant reduction in general physical activity compared with healthy controls. Assessment of specific activity parameters further revealed the correlates of impairments associated with LLD. Our study suggests that novel wearable technology has the potential to provide an objective way of monitoring real-world function. PMID- 27667665 TI - RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes. AB - Pancreatic islet cells are critical for maintaining normal blood glucose levels, and their malfunction underlies diabetes development and progression. We used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic alpha, beta, delta, and PP cells from non-diabetic and type 2 diabetes organ donors. We identified cell-type-specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human alpha and beta cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community. PMID- 27667664 TI - A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation. AB - Oxidative phosphorylation (OXPHOS) is the major pathway for ATP production in humans. Deficiencies in OXPHOS can arise from mutations in either mitochondrial or nuclear genomes and comprise the largest collection of inborn errors of metabolism. At present we lack a complete catalog of human genes and pathways essential for OXPHOS. Here we introduce a genome-wide CRISPR "death screen" that actively selects dying cells to reveal human genes required for OXPHOS, inspired by the classic observation that human cells deficient in OXPHOS survive in glucose but die in galactose. We report 191 high-confidence hits essential for OXPHOS, including 72 underlying known OXPHOS diseases. Our screen reveals a functional module consisting of NGRN, WBSCR16, RPUSD3, RPUSD4, TRUB2, and FASTKD2 that regulates the mitochondrial 16S rRNA and intra-mitochondrial translation. Our work yields a rich catalog of genes required for OXPHOS and, more generally, demonstrates the power of death screening for functional genomic analysis. PMID- 27667666 TI - Suppressors of Superoxide-H2O2 Production at Site IQ of Mitochondrial Complex I Protect against Stem Cell Hyperplasia and Ischemia-Reperfusion Injury. AB - Using high-throughput screening we identified small molecules that suppress superoxide and/or H2O2 production during reverse electron transport through mitochondrial respiratory complex I (site IQ) without affecting oxidative phosphorylation (suppressors of site IQ electron leak, "S1QELs"). S1QELs diminished endogenous oxidative damage in primary astrocytes cultured at ambient or low oxygen tension, showing that site IQ is a normal contributor to mitochondrial superoxide-H2O2 production in cells. They diminished stem cell hyperplasia in Drosophila intestine in vivo and caspase activation in a cardiomyocyte cell model driven by endoplasmic reticulum stress, showing that superoxide-H2O2 production by site IQ is involved in cellular stress signaling. They protected against ischemia-reperfusion injury in perfused mouse heart, showing directly that superoxide-H2O2 production by site IQ is a major contributor to this pathology. S1QELs are tools for assessing the contribution of site IQ to cell physiology and pathology and have great potential as therapeutic leads. PMID- 27667667 TI - Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes. AB - Hormone-secreting cells within pancreatic islets of Langerhans play important roles in metabolic homeostasis and disease. However, their transcriptional characterization is still incomplete. Here, we sequenced the transcriptomes of thousands of human islet cells from healthy and type 2 diabetic donors. We could define specific genetic programs for each individual endocrine and exocrine cell type, even for rare delta, gamma, epsilon, and stellate cells, and revealed subpopulations of alpha, beta, and acinar cells. Intriguingly, delta cells expressed several important receptors, indicating an unrecognized importance of these cells in integrating paracrine and systemic metabolic signals. Genes previously associated with obesity or diabetes were found to correlate with BMI. Finally, comparing healthy and T2D transcriptomes in a cell-type resolved manner uncovered candidates for future functional studies. Altogether, our analyses demonstrate the utility of the generated single-cell gene expression resource. PMID- 27667669 TI - Analysis of Positive Selection at Single Nucleotide Polymorphisms Associated with Body Mass Index Does Not Support the "Thrifty Gene" Hypothesis. AB - The "thrifty gene hypothesis" suggests genetic susceptibility to obesity arises because of positive selection for alleles that favored fat deposition and survival during famines. We used public domain data to locate signatures of positive selection based on derived allele frequency, genetic diversity, long haplotypes, and differences between populations at SNPs identified in genome-wide association studies (GWASs) for BMI. We used SNPs near the lactase (LCT), SLC24A5, and SLC45A2 genes as positive controls and 120 randomly selected SNPs as negative controls. We found evidence for positive selection (p < 0.05) at nine out of 115 BMI SNPs. However, five of these involved positive selection for the protective allele (i.e., for leanness). The widespread absence of signatures of positive selection, combined with selection favoring leanness at some alleles, does not support the suggestion that obesity provided a selective advantage to survive famines, or any other selective advantage. PMID- 27667668 TI - Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators. AB - To systemically identify long noncoding RNAs (lncRNAs) regulating energy metabolism, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in key metabolic organs in mice under pathophysiologically representative metabolic conditions. Of 4,759 regulated lncRNAs, function oriented filters yield 359 tissue-specifically regulated and metabolically sensitive lncRNAs that are predicted by lncRNA-mRNA correlation analyses to function in diverse aspects of energy metabolism. Specific regulations of liver metabolically sensitive lncRNAs (lncLMS) by nutrients, metabolic hormones, and key transcription factors were further defined in primary hepatocytes. Combining genome-wide screens, bioinformatics function predictions, and cell-based analyses, we developed an integrative roadmap to identify lncRNA metabolic regulators. An lncLMS was experimentally confirmed in mice to suppress lipogenesis by forming a negative feedback loop in the SREBP1c pathway. Taken together, this study supports that a class of lncRNAs function as important metabolic regulators and establishes a framework for systemically investigating the role of lncRNAs in physiological homeostasis. PMID- 27667670 TI - A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development. AB - Nelumbo nucifera, also known as sacred lotus, has primarily been used as food throughout the Asian continent, and its medicinal values have been described in Ayurvedic and Traditional Chinese Medicine. The purpose of this study is to systematically characterize the chemical profiling and pharmacological activities of N. nucifera. Herein, we critically reviewed and analysed the phytochemical and pharmacological reports of N. nucifera. Our search for the keyword 'Nelumbo nucifera pharmacology' in all databases reported in Web of Science yielded 373 results excluding reviews and abstracts in document types. Two hundred and forty three spectrum natural compounds from different parts of N. nucifera belonging to diverse chemical groups, including alkaloids, flavonoids, glycosides, terpenoids, steroids, fatty acids, proteins, minerals, and vitamins have been reported. In addition, distinct pharmacological activities, mainly against cancer, microbial infection, diabetes, inflammation, atherosclerosis, and obesity, have been associated with crude extracts, fractions, and isolated compounds. This review highlights potential use of neferine, liensinine, isoliensinine, and nuciferine in clinical trials. In depth, mechanism of the potential chemical entities from N. nucifera via structure activity relationship needs to be explored to guarantee the stability and safety for the clinical use. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27667671 TI - Rapid desensitization to anakinra-related delayed reaction: Need for a standardized protocol. PMID- 27667672 TI - Passive smoking increased risk of gestational diabetes mellitus independently and synergistically with prepregnancy obesity in Tianjin, China. AB - BACKGROUND: Passive smoking increased type 2 diabetes mellitus risk, but it is uncertain whether it also increased gestational diabetes mellitus (GDM) risk. We aimed to examine the association of passive smoking during pregnancy and its interaction with maternal obesity for GDM. METHODS: From 2010 to 2012, 12 786 Chinese women underwent a 50-g 1-hour glucose challenge test at 24 to 28 weeks of gestation and further underwent a 75-g 2-hour oral glucose tolerance test if the glucose challenge test result was >=7.8 mmol/L. GDM was defined by the International Association of Diabetes and Pregnancy Study Group's cut points. Self-reported passive smoking during pregnancy was collected by a questionnaire. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between maternal obesity and passive smoking was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Significant RERI > 0, AP > 0, or S > 1 indicated additive interaction. RESULTS: A total of 8331 women (65.2%) were exposed to passive smoking during pregnancy. More women exposed to passive smoking developed GDM than nonexposed women (7.8% versus 6.3%, P = 0.002) with an adjusted OR of 1.29 (95%CI, 1.11 to 1.50). Compared with nonobesity and nonpassive smoking, prepregnancy obesity and passive smoking was associated with GDM risk with an adjusted OR of 3.09 (95%CI, 2.38 4.02) with significant additive interaction (P < .05 for RERI and AP). CONCLUSIONS: Passive smoking during pregnancy increased GDM risk in Chinese women independently and synergistically with prepregnancy obesity. PMID- 27667673 TI - An Electrophilic Reagent for the Direct Introduction of the SCF2 PO(OEt)2 Group to Molecules. AB - An unprecedented electrophilic difluoromethylthiolating reagent (MesNHSCF2 PO(OEt)2 ) was designed. Under mild and metal-free conditions, this new reagent reacted with various nucleophiles, thus offering an efficient and operationally simple tool for the construction of C-SCF2 PO(OR)2 , N-SCF2 PO(OR)2 , and S-SCF2 PO(OR)2 bonds. Finally, thanks to this new methodology, the synthesis of the non stereoidal anti-inflammatory diflumidone was achieved. PMID- 27667675 TI - Comparative analysis of three histologic grading methods for squamous cell carcinoma of the lip. AB - OBJECTIVES: The aim of this study was to evaluate three histologic grading methods for squamous cell carcinoma (SCC) of the lip, the conventional three grade model proposed by the World Health Organization, tumor budding and depth of invasion (BD) model, and histologic risk assessment (HRA) model, and to correlate them with prognosis. MATERIALS AND METHODS: Fifty-three patients with lip SCC were evaluated. RESULTS: The mean age was 65 years, 69.8% of the participants were men, and 66.0% of the patients had early-stage tumors. Using the BD and conventional three-grade methods, 52.8% and 64.2% of the cases were graded as low risk, respectively. The HRA model graded 54.7% of the cases as medium risk. In the BD model, the higher histologic grade was associated with worse prognosis (P = 0.045). Overall survival at 5 years was 87.8%. Tumor size (T3 + T4) and lymph node involvement (N+) were associated with reduced overall survival and recurrence-free survival (RFS) (P = 0.002 and 0.005; 0.007 and 0.01, respectively). Surgical treatment combined with radiotherapy was associated with lower RFS (P = 0.03). CONCLUSIONS: High-grade lip SCC in advanced stages is associated with a poor prognosis. The BD model is a simple and effective tool for the prognostic evaluation of lip SCC. PMID- 27667676 TI - Presence of plastic particles in waterbirds faeces collected in Spanish lakes. AB - Plastic intake by marine vertebrates has been widely reported, but information about its presence in continental waterfowl is scarce. Here we analyzed faeces of waterbirds species (European coot, Fulica atra, mallard, Anas platyrhynchos and shelduck, Tadorna tadorna) for plastic debris in five wetlands in Central Spain. We collected 89 faeces of shelduck distributed in four lakes, 43.8% of them presented plastic remnants. Sixty percent of 10 faeces of European coot and 45% of 40 faeces of mallard contained plastic debris. Plastic debris found was of two types, threads and fragments, and were identified as remnants of plastic objects used in agricultural fields surrounding the lakes. Differences in prevalence of plastic in faeces, number of plastic pieces per excrement and size of the plastic pieces were not statistically significant between waterfowl species. Thus, our results suggest that plastic may also be frequently ingested by waterfowl in continental waters, at least in our study area. Future studies should address this potential problem for waterbird conservation in other wetlands to evaluate the real impact of this pollutant on waterbirds living in inland water. PMID- 27667674 TI - Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons. AB - Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID- 27667677 TI - Evaluation of cytotoxic and genotoxic activity of fungicide formulation Tango(r) Super in bovine lymphocytes. AB - Tango(r) Super is a two-compound fungicide formulation widely employed in grain protection. However, details of Tango(r) Super effects on cell cultures have not been fully investigated. In this study, bovine lymphocytes were exposed to a concentration range 0.5; 1.5; 3; 6; and 15 MUg mL-1 for 4 h to assess the cytotoxicity and genotoxicity of the fungicide. Our experiments revealed that this fungicide treatment reduced cell viability, decreased cell proliferation and provoked apoptotic cell death. Cell cycle analysis showed predominant accumulation of cells in the G0/G1 phase of the cell cycle. The fungicide was able to induce mitochondrial superoxide production accompanied by elevated levels of carbonylated proteins and changes in the lipid membrane composition. The fungicide did not induce micronuclei production, but stimulated both DNA double strand breaks and the formation of p53 binding protein, which is accumulated during the DNA repair process at the site of double-strand breaks. Based on the obtained data we suppose that the fungicide-induced DNA damage is the result of oxidative stress, which may contribute to higher occurrence of apoptotic cell death. Because ergosterol biosynthesis-inhibiting fungicides are widely used in agriculture to ensure higher crop yields and may cause health impairment of animals and humans, there is a need for further testing to elucidate their potential genotoxic effects using in vivo and/or in vitro systems. PMID- 27667678 TI - Evaluating the suitability of different environmental samples for tracing atmospheric pollution in industrial areas. AB - Samples of lichens, snow and particulate matter (PM10, 24 h) are used for the source identification of air pollution in the heavily industrialized region of Ostrava, Upper Silesia, Czech Republic. An integrated approach that uses different environmental samples for metal concentration and Pb isotope analyses was applied. The broad range of isotope ratios in the samples indicates a combination of different pollution sources, the strongest among them being the metallurgical industry, bituminous coal combustion and traffic. Snow samples are proven as the most relevant indicator for tracing metal(loid)s and recent local contamination in the atmosphere. Lichens can be successfully used as tracers of the long-term activity of local and remote sources of contamination. The combination of PM10 with snow can provide very useful information for evaluation of current pollution sources. PMID- 27667679 TI - Impact of micropollutants on the life-history traits of the mosquito Aedes aegypti: On the relevance of transgenerational studies. AB - Hazard assessment of chemical contaminants often relies on short term or partial life-cycle ecotoxicological tests, while the impact of low dose throughout the entire life cycle of species across multiple generations has been neglected. This study aimed at identifying the individual and population-level consequences of chronic water contamination by environmental concentrations of three organic micropollutants, ibuprofen, bisphenol A and benzo[a]pyrene, on Aedes aegypti mosquito populations in experimental conditions. Life-history assays spanning the full life-cycle of exposed individuals and their progeny associated with population dynamics modelling evidenced life-history traits alterations in unexposed progenies of individuals chronically exposed to 1 MUg/L ibuprofen or 0.6 MUg/L benzo[a]pyrene. The progeny of individuals exposed to ibuprofen showed an accelerated development while the progeny of individuals exposed to benzo[a]pyrene showed a developmental acceleration associated with an increase in mortality rate during development. These life-history changes due to pollutants exposure resulted in relatively shallow increase of Ae. aegypti asymptotic population growth rate. Multigenerational exposure for six generations revealed an evolution of population response to ibuprofen and benzo[a]pyrene across generations, leading to a loss of previously identified transgenerational effects and to the emergence of a tolerance to the bioinsecticide Bacillus turingiensis israelensis (Bti). This study shed light on the short and long term impact of environmentally relevant doses of ibuprofen and benzo[a]pyrene on Ae. aegypti life-history traits and insecticide tolerance, raising unprecedented perspectives about the influence of surface water pollution on vector-control strategies. Overall, our approach highlights the importance of considering the entire life cycle of organisms, and the necessity to assess the transgenerational effects of pollutants in ecotoxicological studies for ecological risk assessment. Finally, this multi-generational study gives new insight about the influence of surface water pollution on microevolutionary processes. PMID- 27667680 TI - Acute exposure to a quinalphos containing insecticide (convoy) causes genetic damage and nuclear changes in peripheral erythrocytes of silver barb, Barbonymus gonionotus. AB - The present study was aimed to assess the genotoxic effect in fish caused by convoy, an insecticide commercial formulation containing quinalphos, present in the aquatic waterbody. For this purpose a freshwater teleost, silver barb was exposed to sublethal concentrations (25% and 50% of LC50) of convoy and erythrocytic cellular abnormalities (ECA) and erythrocytic nuclear abnormalities (ENA) tests were performed in addition to the commonly used micronucleus (MN) assay using peripheral erythrocytes and DNA contents in the different tissues after 1, 24, 36, 48, and 72 h of exposures. The obtained results indicated that acute exposure of different sub lethal concentrations of convoy to the fish resulted in significant alterations of erythrocytes as well as significant reduction of DNA contents in blood and vital organs and tissues, such as the brain, liver, kidney and muscle. Compared to each treatment excluding control group, frequencies of ECA, ENA, and MN were found to be elevated with exposure time of the doses. From this study, we conclude that convoy is a hazardous chemical to silver barb. Bioassays can be used as a tool for screening aquatic pollution, especially for insecticides. PMID- 27667681 TI - Towards a new orientation: a qualitative longitudinal study of an intensive care recovery programme. AB - AIMS AND OBJECTIVES: To describe the patient experience of ICU recovery from a longitudinal perspective by analysing follow-up consultations at three time points. BACKGROUND: After a stay in the intensive care unit, patients risk physical and psychological problems during recovery. Follow-up after intensive care has emerged to aid psychological recovery, and improve health-related quality of life. More insight is needed into the mechanisms of intensive care recovery. DESIGN: A descriptive multicenter longitudinal qualitative design. METHODS: A subsample of 36 consultations with 12 patients strategically selected from a randomised controlled trial on intensive care recovery from 10 Danish intensive care units. Data were generated during an ICU recovery programme including three consultations (at 1-3, 4-5, 9-11 months). First consultation was face-to-face using patient photographs to aid memory. Second and third consultations were by telephone using reflection sheets to focus dialogue. Thematic analysis and narrative theory were used to explore mechanisms of recovery using audio-recordings of consultations, patient photographs and reflection sheets as the sources of data. RESULTS: The basic narrative of recovery was 'toward a trajectory of new orientation'. This narrative contained the chronological narratives of being 'at death's door', 'still not out of the woods' and 'on the road to recovery'. The road to recovery was described as downhill, steady-state or progressive. New orientation was obtained in steady state or progressive recovery. CONCLUSIONS: This study provides a contemporary understanding of the process of intensive care recovery. Recovery evolves through narratives of mortal danger, risk of relapse and moving forward towards a new orientation in life. RELEVANCE TO CLINICAL PRACTICE: These findings enable health care professionals to understand what patients experience during stages of recovery. This is important to improve health care professionals in the assessment of long-term outcome, and management of patients after intensive care. PMID- 27667682 TI - Opioid overdose leading to intensive care unit admission: Epidemiology and outcomes. PMID- 27667683 TI - Loss of IFN-gamma Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy. AB - Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-gamma, which is a critical cytokine for host immune responses. However, the role of IFN-gamma signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here, we demonstrate that patients identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-gamma pathway genes. Furthermore, mice bearing melanoma tumors with knockdown of IFN-gamma receptor 1 (IFNGR1) have impaired tumor rejection upon anti-CTLA-4 therapy. These data highlight that loss of the IFN-gamma signaling pathway is associated with primary resistance to anti-CTLA-4 therapy. Our findings demonstrate the importance of tumor genomic data, especially IFN-gamma related genes, as prognostic information for patients selected to receive treatment with immune checkpoint therapy. PMID- 27667686 TI - Potent, Reversible, and Specific Chemical Inhibitors of Eukaryotic Ribosome Biogenesis. AB - All cellular proteins are synthesized by ribosomes, whose biogenesis in eukaryotes is a complex multi-step process completed within minutes. Several chemical inhibitors of ribosome function are available and used as tools or drugs. By contrast, we lack potent validated chemical probes to analyze the dynamics of eukaryotic ribosome assembly. Here, we combine chemical and genetic approaches to discover ribozinoindoles (or Rbins), potent and reversible triazinoindole-based inhibitors of eukaryotic ribosome biogenesis. Analyses of Rbin sensitivity and resistance conferring mutations in fission yeast, along with biochemical assays with recombinant proteins, provide evidence that Rbins' physiological target is Midasin, an essential ~540-kDa AAA+ (ATPases associated with diverse cellular activities) protein. Using Rbins to acutely inhibit or activate Midasin function, in parallel experiments with inhibitor-sensitive or inhibitor-resistant cells, we uncover Midasin's role in assembling Nsa1 particles, nucleolar precursors of the 60S subunit. Together, our findings demonstrate that Rbins are powerful probes for eukaryotic ribosome assembly. PMID- 27667685 TI - A Functional Role for Antibodies in Tuberculosis. AB - While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcgammaRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control. PMID- 27667687 TI - Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. AB - Activated macrophages undergo metabolic reprogramming, which drives their pro inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state. PMID- 27667684 TI - Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. AB - Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases. Using chromatin interaction sequencing, massively parallel reporter assays (MPRA), and transgenic mice, we identified disease linked, biallelic HAR mutations in active enhancers for CUX1, PTBP2, GPC4, CDKL5, and other genes implicated in neural function, ASD, or both. Our data provide genetic evidence that specific HARs are essential for normal development, consistent with suggestions that their evolutionary changes may have altered social and/or cognitive behavior. PAPERCLIP. PMID- 27667689 TI - Right ventricular involvement in feline hypertrophic cardiomyopathy. AB - OBJECTIVES: To evaluate right ventricular (RV) wall thickness and chamber dimensions in cats with hypertrophic cardiomyopathy (HCM). ANIMALS: One hundred fifty-one healthy control cats and 200 cats with HCM. METHODS: Retrospective, observational, clinical cohort study. Two-dimensional echocardiograms from all cats were analyzed. Right atrial diameter, RV free wall thickness, and RV chamber diameter were quantified using multiple imaging views. Conventional (mean +/- 2 standard deviations) and allometrically scaled (Y = a * Mb) reference values were determined in normal cats and compared to values found in cats with HCM. Linear and logistic regression, multivariate regression, and mixed model analysis were performed to identify associations between RV wall thickness and severity of left ventricular (LV) hypertrophy, clinical severity of HCM, and presence of pleural effusion. RESULTS: Mean RV wall thickness was increased in HCM (p<0.001). Considering increased RV wall thickness in at least one segment, 94 (47%) and 112 (56%) cats with HCM had RV hypertrophy using upper reference limits based on mean + 2 standard deviations or allometric scaling, respectively. There was an association between severity of LV and RV hypertrophy (p<0.05). Left-sided congestive heart failure (n = 58) was associated with increased RV wall thickness in all segments compared to cats with preclinical HCM (p<0.001). Body weight had negligible effects on RV wall thickness (R2 0.08-0.17, p<0.001), whereas age and breed had no effect (p>0.05) in control cats. CONCLUSIONS: Increased RV wall thickness is common in cats with HCM and relates to severity of LV hypertrophy and clinical status. PMID- 27667688 TI - The Anopheles FBN9 immune factor mediates Plasmodium species-specific defense through transgenic fat body expression. AB - Mosquitoes have a multifaceted innate immune system that is actively engaged in warding off various pathogens, including the protozoan malaria parasite Plasmodium. Various immune signaling pathways and effectors have been shown to mediate a certain degree of defense specificity against different Plasmodium species. A key pattern recognition receptor of the Anopheles gambiae immune system is the fibrinogen domain-containing immunolectin FBN9, which has been shown to be transcriptonally induced by Plasmodium infection, and to mediate defense against both rodent and human malaria parasites and bacteria. Here we have further studied the defense specificity of FBN9 using a transgenic approach, in which FBN9 is overexpressed in the fat body tissue after a blood meal through a vitellogenin promoter. Interestingly, the Vg-FBN9 transgenic mosquitoes showed increased resistance only to the rodent parasite P. berghei, and not to the human parasite P. falciparum, pointing to differences in the mosquito's defense mechanisms against the two parasite species. The Vg-FBN9 transgenic mosquitoes were also more resistant to infection with both Gram-positive and Gram-negative bacteria and showed increased longevity when infected with P. berghei. Our study points to the importance of both experimentally depleting and enriching candidate anti-Plasmodium effectors in functional studies in order to ascertain their suitability for the development of transgenic mosquito-based malaria control strategies. PMID- 27667690 TI - Crystal Structure of a Type IV Pilus Assembly ATPase: Insights into the Molecular Mechanism of PilB from Thermus thermophilus. AB - Type IV pili (T4P) mediate bacterial motility and virulence. The PilB/GspE family ATPases power the assembly of T4P and type 2 secretion systems. We determined the structure of the ATPase region of PilB (PilBATP) in complex with ATPgammaS to provide a model of a T4P assembly ATPase and a view of a PilB/GspE family hexamer at better than 3-A resolution. Spatial positioning and conformations of the protomers suggest a mechanism of force generation. All six PilBATP protomers contain bound ATPgammaS. Two protomers form a closed conformation poised for ATP hydrolysis. The other four molecules assume an open conformation but separate into two pairs with distinct active-site accessibilities. We propose that one pair represents the post-hydrolysis phase while the other pair appears poised for ADP/ATP exchange. Collectively, the data suggest that T4P assembly is powered by coordinating concurrent substrate binding with ATP hydrolysis across the PilB hexamer. PMID- 27667691 TI - A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis. AB - The I domain of HslU sits above the AAA+ ring and forms a funnel-like entry to the axial pore, where protein substrates are engaged, unfolded, and translocated into HslV for degradation. The L199Q I-domain substitution, which was originally reported as a loss-of-function mutation, resides in a segment that appears to adopt multiple conformations as electron density is not observed in HslU and HslUV crystal structures. The L199Q sequence change does not alter the structure of the AAA+ ring or its interactions with HslV but increases I-domain susceptibility to limited endoproteolysis. Notably, the L199Q mutation increases the rate of ATP hydrolysis substantially, results in slower degradation of some proteins but faster degradation of other substrates, and markedly changes the preference of HslUV for initiating degradation at the N or C terminus of model substrates. Thus, a structurally dynamic region of the I domain plays a key role in controlling protein degradation by HslUV. PMID- 27667692 TI - Common Evolutionary Origin of Procapsid Proteases, Phage Tail Tubes, and Tubes of Bacterial Type VI Secretion Systems. AB - Many large viruses, including tailed dsDNA bacteriophages and herpesviruses, assemble their capsids via formation of precursors, called procapsids or proheads. The prohead has an internal core, made of scaffolding proteins, and an outer shell, formed by the major capsid protein. The prohead usually contains a protease, which is activated during capsid maturation to destroy the inner core and liberate space for the genome. Here, we report a 2.0 A resolution structure of the pentameric procapsid protease of bacteriophage T4, gene product (gp)21. The structure corresponds to the enzyme's pre-active state in which its N terminal region blocks the catalytic center, demonstrating that the activation mechanism involves self-cleavage of nine N-terminal residues. We describe similarities and differences between T4 gp21 and related herpesvirus proteases. We found that gp21 and the herpesvirus proteases have similarity with proteins forming the tubes of phage tails and bacterial type VI secretion systems, suggesting their common evolutionary origin. PMID- 27667693 TI - Computational Repacking of HIF-2alpha Cavity Replaces Water-Based Stabilized Core. AB - Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors central to hypoxia response and cancer development. Within the HIF-2 complex, one domain (HIF-2alpha PAS-B) contains a large (290 A3) buried cavity filled with water molecules within its hydrophobic core. Such cavities are uncommon except in the case of ligand-binding proteins, leading to the hypothesis that HIF-2alpha can be regulated by small molecules. The development of artificial HIF-2alpha inhibitors validates this hypothesis but raises questions about the impact of this cavity on HIF-2alpha PAS-B structure and function. To answer these points, we used computational methods to construct a repacked protein containing a smaller cavity within the native fold. Experimental validation of a five-mutation variant confirms achieving these objectives and stabilizing the folded structure. Complementary functional data establish that ligands cannot bind this variant although heterodimerization remains unchanged. Altogether, our strategy innovatively addresses the roles of solvated cavities in maintaining protein stability and function. PMID- 27667694 TI - A Phosphomimetic Mutation Stabilizes SOD1 and Rescues Cell Viability in the Context of an ALS-Associated Mutation. AB - The majority of amyotrophic lateral sclerosis (ALS)-related mutations in the enzyme Cu,Zn superoxide dismutase (SOD1), as well as a post-translational modification, glutathionylation, destabilize the protein and lead to a misfolded oligomer that is toxic to motor neurons. The biophysical role of another physiological SOD1 modification, T2-phosphorylation, has remained a mystery. Here, we find that a phosphomimetic mutation, T2D, thermodynamically stabilizes SOD1 even in the context of a strongly SOD1-destabilizing mutation, A4V, one of the most prevalent and aggressive ALS-associated mutations in North America. This stabilization protects against formation of toxic SOD oligomers and positively impacts motor neuron survival in cellular assays. We solve the crystal structure of T2D-SOD1 and explain its stabilization effect using discrete molecular dynamics (DMD) simulations. These findings imply that T2-phosphorylation may be a plausible innate cellular protection response against SOD1-induced cytotoxicity, and stabilizing the SOD1 native conformation might offer us viable pharmaceutical strategies against currently incurable ALS. PMID- 27667695 TI - Atg5-dependent autophagy plays a protective role against methylmercury-induced cytotoxicity. AB - Methylmercury (MeHg) is a widespread environmental pollutant and causes a serious hazard to health worldwide. However, molecular mechanisms underlying MeHg toxicity remain elusive. We show that MeHg reduced mouse embryonic fibroblast (MEF) viability in a dose-dependent manner. Furthermore, MeHg treatment increased levels of autophagy markers LC3-II and p62, possibly by acting on the MAPKs signaling pathway in several cell types. MeHg exposure elevated the number of LC3 puncta in stable GFP-LC3 MEFs and the number of autophagic vacuoles. The accumulation of LC3-II and p62 increased further when complementing MeHg with autophagy inhibitor, chloroquine. Moreover, we found that autophagy-related gene 5-deficient (Atg5-/-) MEFs exhibited higher sensitivity and higher levels of p62 compared to their wild-type counterparts following MeHg exposure. This suggested that p62 was upregulated at the transcription level by MeHg and degraded by Atg5 dependent autophagy. Our data demonstrate that MeHg exposure promotes autophagy, and Atg5-dependent autophagy serves to protect cells from MeHg cytotoxicity. PMID- 27667696 TI - Inflammation-Induced Adhesin-Receptor Interaction Provides a Fitness Advantage to Uropathogenic E. coli during Chronic Infection. AB - Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose beta1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis. However, FmlH provided a fitness advantage during chronic cystitis, which is manifested as persistent bacteriuria, high bladder bacterial burdens, and chronic inflammation. In situ binding confirmed that FmlH bound avidly to the inflamed, but not the naive bladder. In accordance with its pathogenic profile, vaccination with FmlH significantly protected mice from chronic cystitis. Thus, UPEC employ separate CUP pili to adapt to the rapidly changing niche during bladder infection. PMID- 27667697 TI - A Eukaryotic-like Serine/Threonine Kinase Protects Staphylococci against Phages. AB - Organisms from all domains of life are infected by viruses. In eukaryotes, serine/threonine kinases play a central role in antiviral response. Bacteria, however, are not commonly known to use protein phosphorylation as part of their defense against phages. Here we identify Stk2, a staphylococcal serine/threonine kinase that provides efficient immunity against bacteriophages by inducing abortive infection. A phage protein of unknown function activates the Stk2 kinase. This leads to the Stk2-dependent phosphorylation of several proteins involved in translation, global transcription control, cell-cycle control, stress response, DNA topology, DNA repair, and central metabolism. Bacterial host cells die as a consequence of Stk2 activation, thereby preventing propagation of the phage to the rest of the bacterial population. Our work shows that mechanisms of viral defense that rely on protein phosphorylation constitute a conserved antiviral strategy across multiple domains of life. PMID- 27667699 TI - The DNP project: Quandaries for nursing scholars. AB - BACKGROUND: In the evolving Doctor of Nursing Practice (DNP) movement, there continues to be a lack of agreement about the final scholarly project. PURPOSE: This study identifies and describes the faculty practices and challenges related to the DNP project across the United States. METHODS: In a descriptive research study, 90 DNP program directors responded to an online survey describing the environment of the DNP program with emphasis on the final scholarly project. DISCUSSION: According to the respondents, 87% of faculty are somewhat or very dissatisfied with the DNP project. Elements that may contribute to the dissatisfaction are the reported lack of faculty knowledge of evidence-based practice and quality improvement, lack of consensus on the DNP project, lack of faculty resources for DNP projects, challenges with clinical sites for the DNP project, and students' scholarly writing skills. CONCLUSION: It is imperative to have academic/practice faculty oriented to DNP concepts; achieve consensus on the project title, type, depth, and outcomes; and have an ongoing dialog regarding DNP project design, execution, and challenges. Project implementation models need to be appropriate for the escalating DNP enrollment. Program support related to institutional review board relationships, student writing and statistical skills, and program-practice site partnerships are needed. PMID- 27667700 TI - Determinants for effective collaboration among DNP- and PhD-prepared faculty. AB - BACKGROUND: Uncertainty exists surrounding collaborative relations among Doctor of Nursing Practice (DNP)- and Doctor of Philosophy (PhD)-prepared faculty. PURPOSE: This qualitative study explored the attitudes and determinants for effective collaboration among doctoral-prepared nursing faculty. METHODS: Focus groups were conducted using a convenience sample of doctoral faculty who taught in either/both DNP or PhD programs. Focus group questions were derived to identify interpersonal, organizational, and systemic determinants of collaboration. Data were transcribed and content analyzed using Kruger and Casey methods. RESULTS: Four focus groups included 41 faculty members from two metro area university medical centers. Five themes emerged: (a) DNP not well understood, (b) confusion surrounding research, (c) opportunities for collaboration, (d) lack of structural support, and (e) personal characteristics and attitudes. DISCUSSION: Interpersonal relationships, organizational structures, and systemic impacts have both positive and negative influences on successful collaboration among DNP- and PhD-prepared faculty. CONCLUSION: Collaborative efforts are needed for advancing the profession. PMID- 27667701 TI - Cannula-Assisted, Transabdominal Ultrasound-Guided Inferior Vena Cava Recanalization in Inferior Vena Cava Occlusion. AB - We describe a novel technique for facilitating recanalization of intrahepatic inferior vena cava (IVC) via the transjugular approach in patients with short segmental hepatic IVC occlusion, where a transjugular liver biopsy cannula provides additional support to the catheter-wire combination and trans-abdominal ultrasound helps in positioning the tip of the cannula at the stump of suprahepatic IVC. PMID- 27667702 TI - Cross-Reactions Between Allopurinol and Febuxostat. PMID- 27667698 TI - Data-Driven Phenotypic Categorization for Neurobiological Analyses: Beyond DSM-5 Labels. AB - BACKGROUND: Data-driven approaches can capture behavioral and biological variation currently unaccounted for by contemporary diagnostic categories, thereby enhancing the ability of neurobiological studies to characterize brain behavior relationships. METHODS: A community-ascertained sample of individuals (N = 347, 18-59 years of age) completed a battery of behavioral measures, psychiatric assessment, and resting-state functional magnetic resonance imaging in a cross-sectional design. Bootstrap-based exploratory factor analysis was applied to 49 phenotypic subscales from 10 measures. Hybrid hierarchical clustering was applied to resultant factor scores to identify nested groups. Adjacent groups were compared via independent samples t tests and chi-square tests of factor scores, syndrome scores, and psychiatric prevalence. Multivariate distance matrix regression examined functional connectome differences between adjacent groups. RESULTS: Reduction yielded six factors, which explained 77.8% and 65.4% of the variance in exploratory and constrained exploratory models, respectively. Hybrid hierarchical clustering of these six factors identified two, four, and eight nested groups (i.e., phenotypic communities). At the highest clustering level, the algorithm differentiated functionally adaptive and maladaptive groups. At the middle clustering level, groups were separated by problem type (maladaptive groups; internalizing vs. externalizing problems) and behavioral type (adaptive groups; sensation-seeking vs. extraverted/emotionally stable). Unique phenotypic profiles were also evident at the lowest clustering level. Group comparisons exhibited significant differences in intrinsic functional connectivity at the highest clustering level in somatomotor, thalamic, basal ganglia, and limbic networks. CONCLUSIONS: Data-driven approaches for identifying homogenous subgroups, spanning typical function to dysfunction, not only yielded clinically meaningful groups, but also captured behavioral and neurobiological variation among healthy individuals. PMID- 27667703 TI - Intraperitoneal injection urocortin-3 reduces the food intake of Siberian sturgeon (Acipenser baerii). AB - Urocortin-3 (UCN3), one of the corticotropin releasing factor (CRF) family peptides, which was discovered in 2001, has a variety of biological functions. However, the researches of UCN3 in fish were scarce. In order to understand whether UCN3 play a role in regulating food intake in fish, we first cloned the ucn3 cDNAs sequence of Siberian sturgeon (Acipenser baerii Brandt), and investigated the ucn3 mRNA levels in 11 tissues. The Siberian sturgeon ucn3 cDNA sequence was 1044bp, including an open reading frame (ORF) of 447bp that encoded 148 amino acids with a mature peptide of 40 amino acids, a 5'-terminal untranslated region (5'-UTR) of 162bp and a 3'-terminal untranslated region (3' UTR) of 435bp. The result of tissue distribution showed that ucn3 widely distributed in 11 tissues with highest expression in brain. We also assessed the effects of periprandial (pre- and post-feeding), fasting and re-feeding on ucn3 mRNAs abundance in brain. The results showed the expression of ucn3 mRNA in brain was significantly elevated after feeding, decreased after fasting 17 days and increased after re-feeding. To further investigate the food intake role of UCN3 in Siberian sturgeon, we performed intraperitoneal (i.p.) injection of Siberian sturgeon UCN3 (SsUCN3) with three doses (60, 120 or 240ng/g) and recorded the food intake. Acute and chronic i.p. injection SsUCN3 reduced the food intake in a dose-dependent pattern. In conclusion, this study indicates that SsUCN3 acts as a satiety factor to inhibit the food intake of Siberian sturgeon. PMID- 27667704 TI - Identification and functional characterization of a pyrokinin neuropeptide receptor in the Lyme disease vector, Ixodes scapularis. AB - Pyrokinin-related peptides are pleiotropic factors that are defined by their conserved C-terminal sequence FXPRL-NH2. The pyrokinin nomenclature derives from their originally identified myotropic actions and, as seen in some family members, a blocked amino terminus with pyroglutamate. The black-legged tick, Ixodes scapularis, is well known as a vector of Lyme disease and various other illnesses; however, in comparison to blood-feeding insects, knowledge on its physiology (along with other Ixodid ticks) is rather limited. In this study, we have isolated, examined the expression profile, and functionally deorphanized the pyrokinin peptide receptor in the medically important tick, I. scapularis. Phylogenetic analysis supports that the cloned receptor is indeed a bona fide member of the pyrokinin-related peptide receptor family. The tick pyrokinin receptor transcript expression is most abundant in the central nervous system (i.e. synganglion), but is also detected in trachea, female reproductive tissues, and in a pooled sample comprised of Malpighian (renal) tubules and the hindgut. Finally, functional characterization of the identified receptor confirmed it as a pyrokinin peptide receptor as it was activated equally by four endogenous pyrokinin-related peptides. The receptor was slightly promiscuous as it was also activated by a peptide sharing some structural similarity, namely the CAPA periviserokinin (CAPA-PVK) peptide. Nonetheless, the I. scapularis pyrokinin receptor required a CAPA-PVK peptide concentration of well over three orders of magnitude to achieve a comparable receptor activation response, which indicates it is quite selective for its native pyrokinin peptide ligands. This study sets the stage for future research to examine the prospective tissue targets identified in order to resolve the physiological roles of this family of peptides in Ixodid ticks. PMID- 27667706 TI - Enhanced in vitro cytotoxicity and anti-tumor activity of vorinostat-loaded pluronic micelles with prolonged release and reduced hepatic and renal toxicities. AB - Vorinostat is the first histone deacetylase inhibitor approved by US FDA for use in cancer therapy. However, its limited aqueous solubility, low permeability, and suboptimal pharmacokinetics hinder its delivery. Thus, in this study, micelles of vorinostat with each of pluronic F68 (PF68) and pluronic F127 (PF127) were developed and optimized based on drug loading and entrapment. The optimized micelles were characterized using Fourier transform infrared spectroscopy (FT IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), zeta analyzer, and electron transmission microscopy. Their in vitro release, stability, in vitro cytotoxicity against HepG2, Caco-2, and MCF-7 cell lines, and finally, in vivo antitumor activity in mice bearing Ehrlich Ascites Carcinoma (EAC) were assessed. The highest entrapment efficiency was 99.09+/-2.16% and 94.19+/-2.37% for micelles of 1:50 drug to polymer ratio with each of PF127 and PF68, respectively. These micelles were nearly spherical with nanoscopic mean diameters of 72.61+/-10.66nm for PF68 and 91.88+/-10.70nm for PF127 with narrow size distribution. The micelles provided prolonged release at phosphate buffer saline pH7.4 up to 24h for PF68 and 72h for PF127. Potentiation of in vitro cytotoxicity of vorinostat was more pronounced with PF127 micelles particularly against MCF-7 cells. Compared with free vorinostat, the micelles with PF127 were more effective in inhibiting tumor growth as well as exhibiting significantly (p<0.05) diminished hepatic and renal toxicities. In conclusion, 1:50 vorinostat PF127 micelles may facilitate i.v. formulations and can be suggested as a promising stable and safe nanoparticulate delivery system with prolonged release and potentiated cytotoxicity. PMID- 27667705 TI - Attention-deficit hyperactivity disorder comorbidity and antidepressant resistance among patients with major depression: A nationwide longitudinal study. AB - The comorbidity between attention deficit hyperactivity disorder (ADHD) and major depression is common. However, the influence of ADHD comorbidity in the response or resistance to antidepressants remains unknown among patients with major depression. 1891 patients with major depression and ADHD and 1891 age-/sex matched patients with major depression only were enrolled and followed for 1 year in our study. Use of antidepressants and ADHD medications during 1-year follow-up period were assessed. Antidepressant resistance was defined as treatment failure in two or more than two different antidepressants for adequate treatment dose and duration. Patients with major depression and ADHD had an increased risk of treatment resistance to antidepressants (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.63-3.32) compared with patients with major depression only after adjusting for demographic characteristics and other psychiatric comorbidities. Regular treatment for ADHD would reduce this risk (OR: 1.76, 95% CI: 0.72-4.27). Anxiety (OR: 3.15, 95% CI: 2.24-4.44) and substance use (OR: 2.45, 95% CI: 1.16 5.17) disorders were also associated with an elevated likelihood of resistance to antidepressants during the follow-up. Patients who had dual diagnoses of major depression and ADHD were more likely to have treatment resistance to antidepressants compared with patients with major depression only. Prompt and regular treatment for ADHD would reduce this risk. PMID- 27667707 TI - Identification of three selenoprotein T paralogs in goldfish (Carassius auratus) and expression analysis in response to environmental stressors. AB - Selenoproteins, which contain the selenocysteine (Sec), play crucial roles in antioxidant protection. In the present study, we have identified and characterized three selenoprotein T paralogs (designated as gfSelT1a, gfSelT1b and gfSelT2) in goldfish, Carassius auratus. The SECIS element was found in the 3'-UTRs of gfSelT1a, gfSelT1b and gfSelT2 mRNA. Sequence analysis showed that they all possess the CxxU motif (where U represents Sec) in the N-terminal. Constitutive expressions of gfSelT1a, gfSelT1b and gfSelT2 were observed in all tissues studied. In liver, gfSelT1a, gfSelT1b and gfSelT2 mRNA expression levels significantly decreased when fasting and increased after re-feeding. The expressions of gfSelT1a, gfSelT1b and gfSelT2 were all inducible by cadmium exposure and H2O2-mediated oxidative stress, except the transcripts of gfSelT1b decreasing with H2O2 stimulation in brain. Furthermore, the expressions of gfSelT1a, gfSelT1b and gfSelT2 consistently increased in spleen but decreased in brain in response to heat stress. However, in liver only gfSelT1a mRNA expression significantly increased. In a word, this is the first report of the presence of three SelT genes in goldfish and their distinct expression patterns in response to environmental stressors. Our results suggest a potential involvement of gfSelT1a, gfSelT1b and gfSelT2 in host protection against environmental stressors including heavy mental, oxidative stress and heat stress in goldfish. PMID- 27667709 TI - Anomalous Enhancement of Mechanical Properties in the Ammonia Adsorbed Defective Graphene. AB - Pure graphene is known as the strongest material ever discovered. However, the unavoidable defect formation in the fabrication process renders the strength of defective graphene much lower (~14%) than that of its perfect counterpart. By means of density functional theory computations, we systematically explored the effect of gas molecules (H2, N2, NH3, CO, CO2 and O2) adsorption on the mechanical strength of perfect/defective graphene. The NH3 molecule is found to play a dominant role in enhancing the strength of defective graphene by up to ~15.6%, while other gas molecules decrease the strength of graphene with varying degrees. The remarkable strength enhancement can be interpreted by the decomposition of NH3, which saturates the dangling bond and leads to charge redistribution at the defect site. The present work provides basic information for the mechanical failure of gas-adsorbed graphene and guidance for manufacturing graphene-based electromechanical devices. PMID- 27667710 TI - Autophagy Beyond Intracellular MHC Class II Antigen Presentation. AB - Autophagy is a group of cellular pathways that deliver cytoplasmic constituents for lysosomal degradation. The peptides generated from these pathways can be presented by MHC II molecules, making autophagy an important source of antigens for CD4+ T cells. In addition, modules of the molecular machinery of autophagy were found in recent years to also influence extracellular antigen processing for MHC Class I and Class II presentation, as well as regulation of MHC Class I surface expression. These studies paint a more complicated picture of how regulation of individual autophagy proteins influences adaptive immunity. The respective pathways, especially in regard to their net outcome for CD4+ helper and CD8+ cytotoxic T cell responses in vivo, will be discussed in this review. PMID- 27667711 TI - Regulation of NKG2D Expression and Signaling by Endocytosis. AB - NKG2D is an activating receptor that can bind to a large number of stress-induced ligands that are expressed in the context of cancer or viral infection. This receptor is expressed on many cytotoxic lymphocytes, and plays a crucial role in antitumor and antiviral immune responses. However, exposure to NKG2D ligand expressing target cells promotes receptor endocytosis, ultimately leading to lysosomal receptor degradation and impairment of NKG2D-mediated functions. Interestingly, before being degraded, internalized receptors can signal from the endosomal compartment, leading to the appropriate activation of cellular functional programs. This review summarizes recent findings on ligand-induced receptor internalization, with particular emphasis on the role of endocytosis in the control of both NKG2D-mediated intracellular signaling and receptor degradation. PMID- 27667708 TI - Drug Treatment of Hypertension: Focus on Vascular Health. AB - Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure (BP) elevation, the vascular system is particularly important because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high BP have greater efficacy for reducing cardiovascular risk than drugs that reduce BP, but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve endothelial function and prevent vascular remodelling. Calcium channel blockers also improve endothelial function, although to a lesser extent than ACEIs and ARBs. Mineralocorticoid receptor blockers improve endothelial function and reduce arterial stiffness, and have recently become more established as antihypertensive drugs. Lifestyle factors are essential in preventing the adverse vascular changes associated with high BP and reducing associated cardiovascular risk. Clinicians and scientists should incorporate these factors into treatment decisions for patients with high BP, as well as in the development of new antihypertensive drugs that promote vascular health. PMID- 27667713 TI - High-sensitivity troponin-T as a prognostic marker after out-of-hospital cardiac arrest - A targeted temperature management (TTM) trial substudy. AB - AIM OF THE STUDY: Predicting outcome of unconscious patients after successful resuscitation is challenging and better prognostic markers are highly needed. Ischemic heart disease is a common cause of out-of-hospital cardiac arrest (OHCA). Whether or not high-sensitivity troponin T (hs-TnT) is a prognostic marker among survivors of OHCA with both ischemic and non-ischemic aetiologies remains to be determined. We sought to evaluate the ability of hs-TnT to prognosticate all-cause mortality, death due to cardiovascular causes or multi organ failure and death due to cerebral causes after OHCA. The influence of the level of target temperature management on hs-TnT as a marker of infarct size was also assessed. METHODS: A total of 699 patients from the targeted temperature management (TTM) trial were included and hs-TnT was analyzed in blood samples from 24, 48 and 72h after return of spontaneous circulation (ROSC). The endpoints were 180 day all-cause mortality, death due to cardiovascular causes or multi organ failure and death due to cerebral causes. Subgroups based on the initial ECG after ROSC (STEMI vs all other ECG presentations) were analyzed. RESULTS: Hs TnT was independently associated with all-cause mortality which was driven by death due to cardiovascular causes or multi-organ failure and not cerebral causes (at 48h: OR 1.10, CI 1.01-1.20, p<0.05). Hs-TnT was also an independent predictor of death due to cardiovascular causes or multi-organ failure (at 48h: OR 1.13, CI 1.01-1.26, p<0.05). In patients with STEMI, hs-TnT was independently associated with death due to cardiovascular causes or multi-organ failure (at 48h: OR 1.47, CI 1.10-1.95, p<0.01). Targeted temperature management at 33 degrees C was not associated with hs-TnT compared to 36 degrees C. CONCLUSIONS: After OHCA due to both ischemic and non-ischemic causes, hs-TnT is an independent marker of both all-cause mortality and death due to cardiovascular causes or multi-organ failure. Targeted temperature management at 33 degrees C did not reduce hs-TnT compared to 36 degrees C. Hs-TnT may be a marker of poor prognosis after OHCA and this should be taken into consideration in patients that present with high troponin levels. TRIAL REGISTRATION: The TTM-trial is registered and accessible at Clinicaltrials.gov (identifier: NCT01020916). PMID- 27667714 TI - TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A. AB - The members of tripartite-motif containing (TRIM) protein participate in various cellular processes and play an important role in host antiviral function. TRIM proteins exert their antiviral activity either directly by degrading viral proteins through their E3 ligase activity, or indirectly by promoting host innate immunity. This study demonstrated for the first time that TRIM52 is a novel antiviral TRIM protein against Japanese encephalitis virus (JEV) infection. Overexpression of TRIM52 restricted JEV replication in BHK-21 and 293T cells. In addition, JEV nonstructural protein 2A (NS2A) is a protein that interacts with TRIM52. Their interaction degraded NS2A in a proteasome-dependent manner via the E3 ligase activity of TRIM52. Thus, TRIM52 is a novel antiviral TRIM protein, and it exerted antiviral activity against JEV infection by targeting and degrading viral NS2A. PMID- 27667715 TI - A suppressor locus for MODY3-diabetes. AB - Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency. PMID- 27667716 TI - The climatic impact of food consumption in a representative sample of Irish adults and implications for food and nutrition policy. AB - OBJECTIVE: To evaluate the greenhouse gas emissions (GHGE) associated with the diet of Irish adults. DESIGN: GHGE were estimated by applying conversion factors to habitual food consumption data taken from the National Adult Nutrition Survey, which was representative of the population. Descriptive analyses were undertaken for GHGE for the total population, as well as accounting for energy misreporting and across categories of sociodemographic and socio-economic factors and tertiles of emissions. SETTING: Republic of Ireland. SUBJECTS: Adults aged 18-87 years (n 1500). RESULTS: The GHGE derived from daily dietary intakes was estimated as 6.5 kg of CO2 equivalents (CO2eq) per person. Males, younger consumers, those with secondary education and student employment status were associated with significantly higher GHGE. Red meat was the highest contributor to GHGE with 1646 g CO2eq arising from a mean intake of 47 g/d. Dairy and starchy staples were the next largest dietary GHGE sources, with mean daily emissions of 732 g CO2eq and 647 g CO2eq, respectively. The lowest emissions were associated with consumption of vegetables, fruits and legumes/pulses/nuts. CONCLUSIONS: Based on profiling using actual food consumption data, it is evident that one single measure is not sufficient and a range of evidence-based mitigation measures with potential to lower emissions throughout the food chain should be considered. The research contributes towards an improved understanding of the climatic impact of the dietary intakes of Irish adults and can serve to inform a sustainability framework to guide action in food and nutrition policy development. PMID- 27667712 TI - Emerging roles of p53 and other tumour-suppressor genes in immune regulation. AB - Tumour-suppressor genes are indispensable for the maintenance of genomic integrity. Recently, several of these genes, including those encoding p53, PTEN, RB1 and ARF, have been implicated in immune responses and inflammatory diseases. In particular, the p53 tumour- suppressor pathway is involved in crucial aspects of tumour immunology and in homeostatic regulation of immune responses. Other studies have identified roles for p53 in various cellular processes, including metabolism and stem cell maintenance. Here, we discuss the emerging roles of p53 and other tumour-suppressor genes in tumour immunology, as well as in additional immunological settings, such as virus infection. This relatively unexplored area could yield important insights into the homeostatic control of immune cells in health and disease and facilitate the development of more effective immunotherapies. Consequently, tumour-suppressor genes are emerging as potential guardians of immune integrity. PMID- 27667717 TI - Computational understanding and experimental characterization of twice-as-smart quadruplex ligands as chemical sensors of bacterial nucleotide second messengers. AB - A twice-as-smart ligand is a small molecule that experiences a structural switch upon interaction with its target (i.e., smart ligand) that concomitantly triggers its fluorescence (i.e., smart probe). Prototypes of twice-as-smart ligands were recently developed to track and label G-quadruplexes: these higher-order nucleic acid structures originate in the assembly of four guanine(G)-rich DNA or RNA strands, whose stability is imparted by the formation and the self-assembly of G quartets. The first prototypes of twice-as-smart quadruplex ligands were designed to exploit the self-association of quartets, being themselves synthetic G quartets. While their quadruplex recognition capability has been thoroughly documented, some doubts remain about the precise photophysical mechanism that underlies their peculiar spectroscopic properties. Here, we uncovered this mechanism via complete theoretical calculations. Collected information was then used to develop a novel application of twice-as-smart ligands, as efficient chemical sensors of bacterial signaling pathways via the fluorescent detection of naturally occurring extracellular quadruplexes formed by cyclic dimeric guanosine monophosphate (c-di-GMP). PMID- 27667718 TI - Global Phosphoproteomic Analysis Reveals the Involvement of Phosphorylation in Aflatoxins Biosynthesis in the Pathogenic Fungus Aspergillus flavus. AB - Aspergillus flavus is a pathogenic fungus that produces toxic and carcinogenic aflatoxins and is the causative agent of aflatoxicosis. A growing body of evidence indicates that reversible phosphorylation plays important roles in regulating diverse functions in this pathogen. However, only a few phosphoproteins of this fungus have been identified, which hampers our understanding of the roles of phosphorylation in A. flavus. So we performed a global and site-specific phosphoproteomic analysis of A. flavus. A total of 598 high-confidence phosphorylation sites were identified in 283 phosphoproteins. The identified phosphoproteins were involved in various biological processes, including signal transduction and aflatoxins biosynthesis. Five identified phosphoproteins associated with MAPK signal transduction and aflatoxins biosynthesis were validated by immunoblotting using phospho-specific antibodies. Further functional studies revealed that phosphorylation of the MAP kinase kinase kinase Ste11 affected aflatoxins biosynthesis in A. flavus. Our data represent the results of the first global survey of protein phosphorylation in A. flavus and reveal previously unappreciated roles for phosphorylation in the regulation of aflatoxins production. The generated dataset can serve as an important resource for the functional analysis of protein phosphorylation in A. flavus and facilitate the elucidation of phosphorylated signaling networks in this pathogen. PMID- 27667719 TI - Ska3 Ensures Timely Mitotic Progression by Interacting Directly With Microtubules and Ska1 Microtubule Binding Domain. AB - The establishment of physical attachment between the kinetochore and dynamic spindle microtubules, which undergo cycles of polymerization and depolymerization generating straight and curved microtubule structures, is essential for accurate chromosome segregation. The Ndc80 and Ska complexes are the major microtubule binding factors of the kinetochore responsible for maintaining chromosome microtubule coupling during chromosome segregation. We previously showed that the Ska1 subunit of the Ska complex binds dynamic microtubules using multiple contact sites in a mode that allows conformation-independent binding. Here, we show that the Ska3 subunit is required to modulate the microtubule binding capability of the Ska complex (i) by directly interacting with tubulin monomers and (ii) indirectly by interacting with tubulin contacting regions of Ska1 suggesting an allosteric regulation. Perturbing either the Ska3-microtubule interaction or the Ska3-Ska1 interactions negatively influences microtubule binding by the Ska complex in vitro and affects the timely onset of anaphase in cells. Thus, Ska3 employs additional modulatory elements within the Ska complex to ensure robust kinetochore-microtubule attachments and timely progression of mitosis. PMID- 27667721 TI - Using fluorescent dissolved organic matter to trace and distinguish the origin of Arctic surface waters. AB - Climate change affects the Arctic with regards to permafrost thaw, sea-ice melt, alterations to the freshwater budget and increased export of terrestrial material to the Arctic Ocean. The Fram and Davis Straits represent the major gateways connecting the Arctic and Atlantic. Oceanographic surveys were performed in the Fram and Davis Straits, and on the east Greenland Shelf (EGS), in late summer 2012/2013. Meteoric (fmw), sea-ice melt, Atlantic and Pacific water fractions were determined and the fluorescence properties of dissolved organic matter (FDOM) were characterized. In Fram Strait and EGS, a robust correlation between visible wavelength fluorescence and fmw was apparent, suggesting it as a reliable tracer of polar waters. However, a pattern was observed which linked the organic matter characteristics to the origin of polar waters. At depth in Davis Strait, visible wavelength FDOM was correlated to apparent oxygen utilization (AOU) and traced deep-water DOM turnover. In surface waters FDOM characteristics could distinguish between surface waters from eastern (Atlantic + modified polar waters) and western (Canada-basin polar waters) Arctic sectors. The findings highlight the potential of designing in situ multi-channel DOM fluorometers to trace the freshwater origins and decipher water mass mixing dynamics in the region without laborious samples analyses. PMID- 27667720 TI - G9a inhibits MEF2C activity to control sarcomere assembly. AB - In this study, we demonstrate that the lysine methyltransferase G9a inhibits sarcomere organization through regulation of the MEF2C-HDAC5 regulatory axis. Sarcomeres are essential for muscle contractile function. Presently, skeletal muscle disease and dysfunction at the sarcomere level has been associated with mutations of sarcomere proteins. This study provides evidence that G9a represses expression of several sarcomere genes and its over-expression disrupts sarcomere integrity of skeletal muscle cells. G9a inhibits MEF2C transcriptional activity that is essential for expression of sarcomere genes. Through protein interaction assays, we demonstrate that G9a interacts with MEF2C and its co-repressor HDAC5. In the presence of G9a, calcium signaling-dependent phosphorylation and export of HDAC5 to the cytoplasm is blocked which likely results in enhanced MEF2C-HDAC5 association. Activation of calcium signaling or expression of constitutively active CaMK rescues G9a-mediated repression of HDAC5 shuttling as well as sarcomere gene expression. Our results demonstrate a novel epigenetic control of sarcomere assembly and identifies new therapeutic avenues to treat skeletal and cardiac myopathies arising from compromised muscle function. PMID- 27667722 TI - Prevalence of human papillomavirus types, viral load and physical status of HPV16 in head and neck squamous cell carcinoma from the South Swedish Health Care Region. AB - Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74 % of the HPV-positive cases. HPV was detected in 65 % (92/141) and 11 % (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (P<0.0001). HPV was detected in 73 % (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell-1 (range 0.003-1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100 % (17/17) and 68 % (40/58) for those with <1 HPV16 copy cell-1 and >1 HPV16 copy cell-1, respectively (P=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6 %, whereas entirely episomal and mixed virus was detected in 51 and 42 % of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48 %), the episomal HPV16 is salient (93 %) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas. PMID- 27667724 TI - Tuning the Activity of Oxygen in LiNi0.8Co0.15Al0.05O2 Battery Electrodes. AB - Layered transition metal oxides such as LiNi0.8Co 0.15Al0.05O2 (NCA) are highly desirable battery electrodes. However, these materials suffer from thermal runaway caused by deleterious oxygen loss and surface phase transitions when in highly overcharged and overheated conditions, prompting serious safety concerns. Using in situ environmental transmission electron microscopy techniques, we demonstrate that surface oxygen loss and structural changes in the highly overcharged NCA particles are suppressed by exposing them to an oxygen-rich environment. The onset temperature for the loss of oxygen from the electrode particle is delayed to 350 degrees C at oxygen gas overpressure of 400 mTorr. Similar heating of the particles in a reducing hydrogen gas demonstrated a quick onset of oxygen loss at 150 degrees C and rapid surface degradation of the particles. The results reported here illustrate the fundamental mechanism governing the failure processes of electrode particles and highlight possible strategies to circumvent such issues. PMID- 27667723 TI - Improving the understanding and treatment of complex grief: an important issue for psychotraumatology. AB - In the Netherlands, every year 500,000 people are confronted with the death of a close relative. Many of these people experience little emotional distress. In some, bereavement precipitates severe grief, distress, and dysphoria. A small yet significant minority of bereaved individuals develops persistent and debilitating symptoms of persistent complex bereavement disorder (PCBD) (also termed prolonged grief disorder), posttraumatic stress disorder, and depression. Knowledge about early identification of, and preventive care for complex grief has increased. Moreover, in recent years there has been an increase in treatment options for people for whom loss leads to persistent psychological problems. That said, preventive and curative treatments are effective for some, but not all bereaved individuals experiencing distress and dysfunction following loss. This necessitates further research on the development, course, and treatment of various stages of complex grief, including PCBD. PMID- 27667725 TI - Workers with hand dermatitis and workplace training experiences: A qualitative perspective. AB - BACKGROUND: Workplace training may help to prevent contact dermatitis, a common work-related disease. Information on the characteristics of existing workplace training programs and worker perceptions of this training is limited. METHODS: Fourteen workers with suspected occupational contact dermatitis participated in one-on-one, semi-structured interviews. An inductive thematic analysis approach was used to identify interview themes. RESULTS: Workers expressed a desire for hands-on training with content relevant to their job tasks, favored training from supervisors who had practical experience, and were conflicted about employer motivations for providing training. Few workers had received training on skin protection. In many cases, the training workers had received differed greatly from their desired training. CONCLUSIONS: Although, workers with contact dermatitis describe having received workplace training, some question its value and effectiveness. This perspective may be attributed not only to the content and methods of training but also the health and safety culture of the workplace. Am. J. Ind. Med. 60:69-76, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27667726 TI - Social activities are associated with cognitive decline in older Koreans. AB - AIM: Social activity seems to be important for the prevention of cognitive impairment and frailty. The objective of the present study was to investigate whether social activities are associated with the development of cognitive impairment in Korean older people. METHODS: We analyzed data from the Korean National Longitudinal Study on Aging. A total of 2495 Korean community-dwelling older adults (1163 men and 1332 women) aged between 65 and 79 years at the first wave of the Korean National Longitudinal Study on Aging were used for analysis. Cognitive function was assessed by the Mini-Mental State Examination in 2006 and 2012. Multiple logistic regression analysis was carried out by adjusting covariates, such as age, sex, education, employment, Center for Epidemiological Studies-Depression and instrumental activities of daily living scores, and weight loss. RESULTS: Among the participants, 951 participants (38.1%) showed cognitive decline. Compared with those who participated in a large number of group social activities, multivariate-adjusted odds ratios of cognitive decline in those who participated in a moderate and small number of group activities were 1.18 (95% CI 0.93-1.48) and 1.80 (95% CI 1.16-1.90), respectively. Among six types of group social activities, two types (social club/cafe and alumni) showed a significant correlation with less cognitive decline; adjusted odds ratios of the group with a small number of activities were 1.31 (95% CI 1.09-1.56) and 1.46 (95% CI 1.10 1.93), respectively, compared with the group with a large number of activities. Personal social activities and the other four types of activities (religious, political, leisure and volunteer) did not affect the outcome. CONCLUSIONS: Two social group activities (social club/cafe and alumni) were significantly associated with less cognitive decline in older Koreans. Geriatr Gerontol Int 2017; 17: 1191-1196. PMID- 27667727 TI - Exon Junction Complexes: Supervising the Gene Expression Assembly Line. AB - The exon junction complex (EJC) is an RNA-binding protein complex that is assembled and deposited onto mRNAs during splicing. The EJC comprises four core components that bind to not only canonical sites upstream of exon-exon junctions, but also to noncanonical sites at other positions in exons. EJC-associated proteins are recruited by the EJC at different steps of gene expression to execute the multiple functions of the EJC. Recently, new insights have been obtained into how EJCs stimulate pre-mRNA splicing, and mRNA export, translation, and degradation. Furthermore, mutations in EJC core components were shown to result in severe disorders in humans, demonstrating the critical physiological role of the EJC. Hence, the EJC has been identified as an important player in post-transcriptional gene regulation in metazoans. PMID- 27667729 TI - The national landscape of human papillomavirus-associated oropharynx squamous cell carcinoma. AB - The head and neck squamous cell carcinoma (HNC) landscape is evolving with human papillomavirus (HPV) being a rising cause of oropharynx carcinoma (OPC). This study seeks to investigate a national database for HPV-associated oropharynx carcinoma (HPV-OPC). Using the National Cancer Data Base, we analyzed 22,693 patients with HPV-OPC and known HPV status. Chi-square tests and logistic regression models were utilized to examine differences between HPV positive and HPV negative OPC. 14,805 (65.2%) patients were HPV positive. Mean age at presentation was 58.4 years with HPV-HNC patients being 2.8 years younger compared to the HPV-negative cohort (58.4 vs. 61.2 years, p < 0.001). 67.6% of white patients were HPV-positive compared to 42.3% of African American patients and 57.1% of Hispanics (p < 0.001). When combining race and socioeconomic status (SES), we found African American patients in high SES groups had HPV-OPC prevalence that was significantly higher than African American patients in low SES groups (56.9% vs. 36.3%, p < 0.001). Geographic distribution of HPV-OPC was also analyzed and found to be most prevalent in Western states and least prevalent in the Southern states (p < 0.001). The distribution of HPV-OPC is variable across the country and among racial and socioeconomic groups. A broad understanding of these differences in HPV-OPC should drive educational programs and improve clinical trials that benefit both prevention and current treatments. PMID- 27667728 TI - Phytoplasma classification and phylogeny based on in silico and in vitro RFLP analysis of cpn60 universal target sequences. AB - Phytoplasmas are unculturable, phytopathogenic bacteria that cause economic losses worldwide. As unculturable micro-organisms, phytoplasma taxonomy has been based on the use of the 16S rRNA-encoding gene to establish 16Sr groups and subgroups based on the restriction fragment length polymorphism (RFLP) pattern resulting from the digestion of amplicon (in vitro) or sequence (in silico) with seventeen restriction enzymes. Problems such as heterogeneity of the ribosomal operon and the inability to differentiate closely related phytoplasma strains has motivated the search for additional markers capable of providing finer differentiation of phytoplasma strains. In this study we developed and validated a scheme to classify phytoplasmas based on the use of cpn60 universal target (cpn60 UT) sequences. Ninety-six cpn60 UT sequences from strains belonging to 19 16Sr subgroups were subjected to in silico RFLP using pDRAW32 software, resulting in 25 distinctive RFLP profiles. Based on these results we delineated cpn60 UT groups and subgroups, and established a threshold similarity coefficient for groups and subgroups classifying all the strains analysed in this study. The nucleotide identity among the reference strains, the correspondence between in vitro and in silico RFLP, and the phylogenetic relationships of phytoplasma strains based on cpn60 UT sequences are also discussed. PMID- 27667731 TI - Bayesian variable selection and estimation in semiparametric joint models of multivariate longitudinal and survival data. AB - This paper presents a novel semiparametric joint model for multivariate longitudinal and survival data (SJMLS) by relaxing the normality assumption of the longitudinal outcomes, leaving the baseline hazard functions unspecified and allowing the history of the longitudinal response having an effect on the risk of dropout. Using Bayesian penalized splines to approximate the unspecified baseline hazard function and combining the Gibbs sampler and the Metropolis-Hastings algorithm, we propose a Bayesian Lasso (BLasso) method to simultaneously estimate unknown parameters and select important covariates in SJMLS. Simulation studies are conducted to investigate the finite sample performance of the proposed techniques. An example from the International Breast Cancer Study Group (IBCSG) is used to illustrate the proposed methodologies. PMID- 27667730 TI - Self-navigated 4D cartesian imaging of periodic motion in the body trunk using partial k-space compressed sensing. AB - PURPOSE: To enable fast and flexible high-resolution four-dimensional (4D) MRI of periodic thoracic/abdominal motion for motion visualization or motion-corrected imaging. METHODS: We proposed a Cartesian three-dimensional k-space sampling scheme that acquires a random combination of k-space lines in the ky/kz plane. A partial Fourier-like constraint compacts the sampling space to one half of k space. The central k-space line is periodically acquired to allow an extraction of a self-navigated respiration signal used to populate a k-space of multiple breathing positions. The randomness of the acquisition (induced by periodic breathing pattern) yields a subsampled k-space that is reconstructed using compressed sensing. Local image evaluations (coefficient of variation and slope steepness through organs) reveal information about motion resolvability. Image quality is inspected by a blinded reading. Sequence and reconstruction method are made publicly available. RESULTS: The method is able to capture and reconstruct 4D images with high image quality and motion resolution within a short scan time of less than 2 min. These findings are supported by restricted-isometry-property analysis, local image evaluation, and blinded reading. CONCLUSION: The proposed method provides a clinical feasible setup to capture periodic respiratory motion with a fast acquisition protocol and can be extended by further surrogate signals to capture additional periodic motions. Retrospective parametrization allows for flexible tuning toward the targeted applications. Magn Reson Med 78:632-644, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27667733 TI - Clinical review of treatment outcomes and patterns of failure with adjuvant radiotherapy in node-positive malignant melanoma. AB - INTRODUCTION: Adjuvant radiotherapy is proven to prevent lymph node field relapse after therapeutic lymphadenectomy for melanoma, but does not improve overall survival based on current data. There remains a high rate of distant relapse. This study reports patterns of failure in patients treated with adjuvant radiotherapy, looking at factors associated with distant metastasis and comparing this to recent literature. METHODS: This retrospective study included patients treated with adjuvant nodal irradiation after lymphadenectomy between June 2012 and March 2015. RESULTS: Twenty-one patients were treated during this period. Median follow-up was 13.5 months. There were no lymph node field recurrences. Distant metastasis (DM) rate was 48%. DM rate was significantly higher (P = 0.027) in patients with extracapsular extension (ECE) (71%) than those without ECE (0%). DM rate was higher in those with a maximum tumour size of >3 cm (71%) than those with tumour size <3 cm (30%) (P = 0.160). Number of nodes, BRAF status or nodal site did not correlate with rate of DM. The median time to DM was 16 weeks after completion of radiotherapy. CONCLUSION: Radiotherapy is well tolerated and effective in regional control. However, patients are at risk of early distant relapse, particularly those with ECE or large tumour size. There are currently no useful prognostic markers to differentiate the risk of regional versus distant recurrence, and the optimal treatment paradigm remains undefined. Research on adjuvant systemic therapies and abscopal effects of radiotherapy have shown improved management of distant metastasis; creating an even greater need for effective regional control strategies. PMID- 27667732 TI - Stable benefits of bilateral over unilateral cochlear implantation after two years: A randomized controlled trial. AB - OBJECTIVES/HYPOTHESIS: To investigate hearing capabilities and self-reported benefits of simultaneous bilateral cochlear implantation (BiCI) compared with unilateral cochlear implantation (UCI) after a 2-year follow-up and to evaluate the learning effect of cochlear implantees over time. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Thirty-eight postlingually deafened adults were included in this study and randomly allocated to either UCI or simultaneous BiCI. Our primary outcome was speech intelligibility in noise, with speech and noise coming from straight ahead (Utrecht-Sentence Test with Adaptive Randomized Roving levels). Secondary outcomes were speech intelligibility in noise with spatially separated sources, speech intelligibility in silence (Dutch phoneme test), localization capabilities and self-reported benefits assessed with different quality of hearing and quality of life (QoL) questionnaires. This article describes the results after 2 years of follow-up. RESULTS: We found comparable results for the UCI and simultaneous BiCI group, when speech and noise were both presented from straight ahead. Patients in the BiCI group performed significantly better than patients in the UCI group, when speech and noise came from different directions (P = .01). Furthermore, their localization capabilities were significantly better. These results were consistent with patients' self reported hearing capabilities, but not with the questionnaires regarding QoL. We found no significant differences on any of the subjective and objective reported outcomes between the 1-year and 2-year follow-up. CONCLUSIONS: This study demonstrates important benefits of simultaneous BiCI compared with UCI that remain stable over time. Bilaterally implanted patients benefit significantly in difficult everyday listening situations such as when speech and noise come from different directions. Furthermore, bilaterally implanted patients are able to localize sounds, which is impossible for unilaterally implanted patients. LEVEL OF EVIDENCE: 1b Laryngoscope, 127:1161-1168, 2017. PMID- 27667734 TI - Chikungunya fever: an emerging viral infection threatening North America and Europe. AB - Since the beginning of the twenty-first century, there has been a rapid rise in the number of cases of chikungunya. Initially limited to islands of the southwestern Indian Ocean, the virus has spread across Africa and into the islands of the Caribbean. Cutaneous symptoms include a morbilliform eruption, hyperpigmented macules, and aphthae-like ulcers. Patients often also experience fever and joint pain. We review the methods for diagnosis, treatment, and prevention of this increasingly prevalent virus now emerging more commonly in Europe and North America. PMID- 27667735 TI - Total and regional adiposity measured by dual-energy X-ray absorptiometry and mortality in NHANES 1999-2006. AB - OBJECTIVE: Associations of overall and regional body fat measured by dual-energy X-ray absorptiometry with total and cause-specific mortality in the National Health and Nutrition Examination Survey (NHANES) 1999-2006 were investigated. METHODS: This study included 9,471 participants (>=20 years) free of major chronic diseases at baseline. Death information was obtained from the National Death Index (mean follow-up duration: 8.8 years). RESULTS: A total of 682 participants died after 12 months since baseline, with 206 and 170 deaths attributed to cardiovascular diseases (CVD) and cancer, respectively. The second quartile of fat mass percentages (FM%) was used as the reference to account for potential nonlinearity. In the multivariate-adjusted model, participants in the highest quartile of total FM% had increased total mortality; hazard ratio (HR; 95% confidence interval, 95% CI) was 1.48 (1.07-2.04; P < 0.05). Higher total and trunk FM%, but not leg FM%, were significantly associated with an increased CVD mortality; HRs (95% CIs) in the highest quartiles of total, trunk, and leg FM% were 2.24 (1.17-4.31), 1.93 (1.02-3.66), and 1.50 (0.77-2.94), respectively. CONCLUSIONS: Higher total body fat was associated with increased total mortality in U.S. adults. Higher total and trunk fat contents were also associated with increased CVD mortality, although fat accumulation in the lower body was not an independent predictor of mortality. PMID- 27667737 TI - New Aspects of the Biology of Neutrophil Extracellular Traps. AB - The formation and release of neutrophil extracellular traps (NETs) discovered in 2004 by Volker Brinkmann and Arturo Zychlinsky cast a new light on the role of neutrophils in the non-specific immune response of the body. This discovery has resulted in the rapid development of neutrophil studies in different bacterial and autoimmune diseases as well as neoplasms. Research is also being performed on the role of different signalling pathways engaged in the induction of NETosis, a unique form of a programmed cell death leading to the creation of NETs. The literature provides information on the structure and composition of neutrophil extracellular traps. This review presents the latest data on NET formation and the role of their key components, as well as describing the intracellular signalling pathways leading to the generation of NETs that have been discovered. PMID- 27667738 TI - Carbopalladation Cascades Using Carbon-Carbon Triple Bonds: Recent Advances to Access Complex Scaffolds. AB - Alkynes are one of the most versatile functional groups as synthetic handles. They allow for a direct access to partially or fully substituted alkenes through difunctionalization reactions. A prominently utilized transformation for these sequences is the carbopalladation of alkynes, which can be followed by various termination steps such as aromatizations, dearomatizations, cross-coupling reactions, or pericyclic processes, amongst others. This Minireview provides an overview of the recent literature published in the field of carbopalladation chemistry, both with a focus on methodology as well as its application in the syntheses of complex molecular scaffolds, natural products, and functional molecules. PMID- 27667736 TI - Impaired virus replication and decreased innate immune responses to viral infections in nasal epithelial cells from patients with allergic rhinitis. AB - The aim of this study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. NECs were obtained from eight patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR-3 and TLR-7/8 agonists. Interferon (IFN)-lambda1, IFN-alpha, IFN-beta and regulated on activation, normal T expressed and secreted (RANTES) release into the cell culture supernatants was assessed at 8, 24 and 48 h upon infection or 8 and 24 h after stimulation with poly(I:C) and R848. mRNA levels of IFNs, RANTES, interferon regulatory transcription factor (IRF)3, IRF7 and viral gene copy number were determined using real-time polymerase chain reaction (RT-PCR). PIV3 but not RV1B replication 48 h after infection was significantly lower (P < 0.01) in NECs from AR patients compared to HC. PIV3 infection induced significantly less IFN-lambda1 (both protein and mRNA) in NECs from AR compared to HC. IFN-beta mRNA expression and RANTES protein release and mRNA expression tended to be smaller in AR compared HC cells in response to both viruses. Stimulation with TLR-3 agonist [poly (I:C)] induced similar IFN-lambda1 and RANTES generation in AR and HC subjects. Viral infections in NECs induced IRF7 expression, which correlated with IFN and RANTES expression. These data suggest that virus proliferation rates and the immune response profile are different in nasal epithelial cells from patients with allergic rhinitis compared to healthy individuals. PMID- 27667739 TI - A novel HLA-B allele, HLA-B*15:399, identified in a Chinese individual. AB - One nucleotide replacement in codon 41 of HLA-B*15:02:01 results in a novel allele, HLA-B*15:399. PMID- 27667741 TI - Quantum Physics Principles and Communication in the Acute Healthcare Setting: A Pilot Study. AB - OBJECTIVE: This pilot study explores whether clinician awareness of quantum physics principles could facilitate open communication between patients and providers. DESIGN: In the spirit of action research, this study was conceptualized with a holistic view of human health, using a mixed method design of grounded theory as an emergent method. SAMPLING: Instrumentation includes surveys and a focus group discussion with twelve registered nurses working in an acute care hospital setting. RESULTS: Findings document that the preliminary core phenomenon, energy as information, influences communication in the healthcare environment. Key emergent themes include awareness, language, validation, open communication, strategies, coherence, incoherence and power. CONCLUSION: Research participants indicate that quantum physics principles provide a language and conceptual framework for improving their awareness of communication and interactions in the healthcare environment. Implications of this pilot study support the feasibility of future research and education on awareness of quantum physics principles in other clinical settings. PMID- 27667742 TI - A SUMO and ubiquitin code coordinates protein traffic at replication factories. AB - Post-translational modifications regulate each step of DNA replication to ensure the faithful transmission of genetic information. In this context, we recently showed that deubiquitination of SUMO2/3 and SUMOylated proteins by USP7 helps to create a SUMO-rich and ubiquitin-low environment around replisomes that is necessary to maintain the activity of replication forks and for new origin firing. We propose that a two-flag system mediates the collective concentration of factors at sites of DNA replication, whereby SUMO and Ubiquitinated-SUMO would constitute "stay" or "go" signals respectively for replisome and accessory factors. We here discuss the findings that led to this model, which have implications for the potential use of USP7 inhibitors as anticancer agents. PMID- 27667743 TI - Case of primary pleural angiosarcoma with malignant seeding along the pleural tap tract. PMID- 27667740 TI - Evaluation of Evolocumab (AMG 145), a Fully Human Anti-PCSK9 IgG2 Monoclonal Antibody, in Subjects With Hepatic Impairment. AB - Evolocumab binds PCSK9, increasing low-density lipoprotein cholesterol (LDL-C) receptors and lowering LDL-C. Target-mediated evolocumab elimination is attributable to PCSK9 binding. As circulating PCSK9 and LDL-C levels are primarily regulated by the liver, we compared evolocumab pharmacokinetics, pharmacodynamics, and safety in individuals with and without hepatic impairment. An open-label, parallel-group study evaluated the pharmacokinetics of evolocumab in hepatic-impaired (Child-Pugh Class A or B) or healthy adults. Participants were classified as having no, mild, or moderate hepatic impairment (n = 8/group) and received a single 140-mg evolocumab dose. Assessments of unbound evolocumab and PCSK9 were made predose and postdose. Adverse events were monitored throughout the study. No significant association was observed between baseline PCSK9 and increasing level of hepatic impairment. No difference in extent and time course of PCSK9 or LDL-C reduction was observed despite an apparent decrease in mean unbound evolocumab exposure with increasing hepatic impairment (Jonckheere-Terpstra trend test; maximum serum concentration P = .18; area under the curve P = .09). Maximum reductions were observed in moderately impaired subjects vs healthy individuals: mean maximum serum concentration -34%; mean area under the concentration-time curve (AUC) -47%. On average, unbound PCSK9 serum concentrations fell by >80% at 4 hours after a single evolocumab dose. Mean (95% confidence interval) maximum LDL-C reductions in the healthy, mild, and moderate groups were -57% (-64% to -48%), -70% (-75% to -63%), and -53% (-61% to -43%), respectively. No safety risks were identified. These results support evolocumab use without dose adjustment in patients with active liver disease and mild or moderate hepatic impairment. PMID- 27667745 TI - Catalytic Asymmetric Csp3 -H Functionalization under Photoredox Conditions by Radical Translocation and Stereocontrolled Alkene Addition. AB - This work demonstrates how photoredox-mediated C(sp3 )-H activation through radical translocation can be combined with asymmetric catalysis. Upon irradiation with visible light, alpha,beta-unsaturated N-acylpyrazoles react with N alkoxyphthalimides in the presence of a rhodium-based chiral Lewis acid catalyst and the photosensitizer fac-[Ir(ppy)3 ] to provide a C-C bond-formation product with high enantioselectivity (up to 97 % ee) and, where applicable, with some diastereoselectivity (3.0:1 d.r.). Mechanistically, the synthetic strategy exploits a radical translocation (1,5-hydrogen transfer) from an oxygen-centered to a carbon-centered radical with a subsequent stereocontrolled radical alkene addition. PMID- 27667744 TI - Carboxylated and undercarboxylated osteocalcin in metabolic complications of human obesity and prediabetes. AB - BACKGROUND: Carboxylated osteocalcin (Gla-OC) participates in bone remodeling, whereas the undercarboxylated form (Glu-OC) takes part in energy metabolism. This study was undertaken to compare the blood levels of Glu-OC and Gla-OC in nonobese, healthy obese, and prediabetic volunteers and correlate it with the metabolic markers of insulin resistance and early markers of inflammation. METHODS: Nonobese (body mass index [BMI] <30 kg/m2 ; n = 34) and obese subjects (30 177 days old; group 2) were implanted with a slow-release deslorelin implant for 273 days. Ovarian function before, during, and after treatment with the implant was assessed by measuring serum progesterone levels 10 days after a challenge injection of a short-acting GnRH (0.8 MUg buserelin intramuscularly) on progesterone levels in peripheral blood. Values more than 4 ng/mL progesterone were considered to verify ovarian function. Animals in group 1 underwent ovariohysterectomy during the second treatment with the implant and the uteri, and ovaries were subjected to histopathologic examination. Endometrial hyperplasia and endometritis were observed in 5 of 7 animals. Nonatretic and atretic follicles at different developmental stages, but no active corpora lutea, were present in the ovaries. Ovariohysterectomy of group 2 animals was performed 2 to 12 months after implant removal. The histopathologic examination of the uterus and ovary of four animals neutered during induced pseudopregnancy showed no signs of uterine disorders. In two animals undergoing ovariohysterectomy 12 months after implant removal, endometritis was present. Their ovaries contained follicles at different developmental stages and corpora albicantia. Reversible suppression of ovarian function can be achieved in female rabbits by the use of GnRH slow-release implants administered before or after puberty. The findings of endometrial hyperplasia and endometritis in seven out of 13 rabbits treated once or twice with the implant may indicate that the development of age-related pathologies of the uterus cannot be prevented by the suppression of ovarian function with a long-acting GnRH implant. PMID- 27667751 TI - Reactive oxygen species-mediated cardiac-reperfusion injury: Mechanisms and therapies. AB - Reperfusion injury is an inherent response to the restoration of blood flow after ischemia. It is a complex process involving numerous mechanisms occurring in the intracellular and extracellular environments, and it is mediated in part by reactive oxygen species (ROS). The imbalance between the cellular formation of free radicals and cells' capacity to defend against them can cause cardiac tissue injuries. In this context, ROS play an essential role in both the organ injury and repair processes. After reperfusion, infiltration into the myocardium of inflammatory leucocytes, such as macrophages and neutrophils, causes further ROS production beyond the initiation of the inflammatory cascade. In this case, ROS overproduction is crucial in cardiac injury, and it can increase the complications related to cardiac reperfusion. In myocardial tissue, ROS can be produced from several sources, such as xanthine oxidase, cytochrome oxidase, cyclooxygenase, mediated unsaturated fatty acid oxidation, oxidation of catecholamines, mitochondrial oxidation, activation of leukocyte nicotinamide adenine dinucleotide phosphate oxidase, iron release, and reduction-oxidation reaction cycling; all of these sources reduce molecular oxygen in the reperfused myocardium. This review discusses about the molecular and therapeutic aspects of cardiac-reperfusion injuries generated by ROS. Experimental and clinical evidence with respect to the use of ischemic preconditioning, Ca2+, nitric oxide, and conventional antioxidants in cardiac-reperfusion injury are summarized, and causal therapy approaches with various antioxidants are discussed. PMID- 27667753 TI - Regional Colonic Transit Pattern Does Not Conclusively Identify Evacuation Disorders in Constipated Patients with Delayed Colonic Transit. AB - Background/Aims: After exclusion of structural diseases, chronic constipation may be associated with normal or slow transit or rectal evacuation disorders. We evaluated: (1) clinical features and anorectal function, (2) difference of regional colonic transit according to the presence or absence of evacuation disorders, and (3) association of colonic transit with gender in patients with objectively slow colonic transit. Methods: We reviewed electronic medical records of 1553 patients with constipation seen by one gastroenterologist from 1994-2015 at a tertiary medical center. We identified patients with slow colonic transit using scintigraphy. Evacuation disorders were identified on clinical examination or anorectal manometry. Colonic compliance and tone were measured in 29 patients. Statistical analysis was by the Mann-Whitney rank sum test. Results: Of the 207 patients (155 females, mean age 41.3 +/- 15.3 [SD] years), 113 had evacuation disorders (ED+ve) and 94 did not (ED-ve). There were no significant differences in colonic transit or gastric emptying between ED+ve or ED-ve; similarly, colonic compliance, tone and responses to neostigmine were not different in ED+ve and ED ve. Conversely, there were significant differences by gender in patients with slow colonic transit: colonic transit, small bowel transit, and gastric emptying (all P < 0.005). Conclusions: Delayed colonic transit does not exclude evacuation disorders in chronic constipation. In chronic constipation and objectively slow colonic transit, females had slower gastric, small bowel, and colonic transit than males. PMID- 27667752 TI - Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample. AB - BACKGROUND: Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. METHODS: The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. RESULTS: 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). CONCLUSIONS: Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children. PMID- 27667754 TI - Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance. AB - Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. PMID- 27667755 TI - HMDSO-plasma coated electrospun fibers of poly(cyclodextrin)s for antifungal dressings. AB - Electrospun mats containing cyclodextrin polymers (poly-alphaCD or poly-betaCD) were developed to act as wound dressings showing tunable release rate of the antifungal agent fluconazole incorporated forming inclusion complexes. Poly alphaCD and poly-betaCD were prepared via cross-linking with epichlorohydrin (EPI) as water-soluble large molecular weight polymers. Then, polyCDs forming complexes with fluconazole were mixed with poly-(epsilon-caprolactone) (PCL) or poly(N-vinylpyrrolidone) (PVP) for electrospinning. Obtained bead-free fibers showed a random distribution, diameters in the 350-850nm range, and a variety of physical stability behaviors in aqueous environment. Mats were coated by hexamethyldisiloxane (HMDSO) plasma polymerization to create a hydrophobic layer that prevented rapid drug diffusion. HMDSO coating was evidenced by the Si content of mat surface (EDX analysis) and by the increase in the water contact angle (up to 130 degrees ). In physiological-mimicking medium, non-treated mats showed burst release of fluconazole, whereas HMDSO-coated mats sustained the release and delayed disintegration of PVP-based mats. Antifungal tests evidenced that both coated and non-coated mats efficiently inhibited the growth of Candida albicans. PMID- 27667756 TI - Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat perfusion. AB - Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was assessed in three small intestinal regions: the upper jejunum, mid-small intestine, and the terminal ileum, using both the SPIP and the Doluisio experimental methods. Excellent correlation was evident between the two approaches, especially in the upper jejunum (R2=0.95). Significant regional-dependent permeability was found in half of drugs studied, illustrating the importance and relevance of segmental dependent intestinal permeability. Despite the differences between the two methods, highly comparable results were obtained by both methods, especially in the medium-high Peff range. In conclusion, the SPIP and the Doluisio method are both equally useful in obtaining crucial segmental-dependent intestinal permeability data. PMID- 27667757 TI - Can lipid nanoparticles improve intestinal absorption? AB - Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. PMID- 27667758 TI - Application of 13C NMR cross-polarization inversion recovery experiments for the analysis of solid dosage forms. AB - Solid-state nuclear magnetic resonance (ssNMR) is a powerful and unique method for analyzing solid forms of the active pharmaceutical ingredients (APIs) directly in their original formulations. Unfortunately, despite their wide range of application, the ssNMR experiments often suffer from low sensitivity and peaks overlapping between API and excipients. To overcome these limitations, the crosspolarization inversion recovery method was successfully used. The differences in the spin-lattice relaxation time constants for hydrogen atoms T1(H) between API and excipients were employed in order to separate and discriminate their peaks in ssNMR spectra as well as to increase the intensity of API signals in low-dose formulations. The versatility of this method was demonstrated by different examples, including the excipients mixture and commercial solid dosage forms (e.g. granules and tablets). PMID- 27667759 TI - B10 cells play a role in the immune modulation of pro- and anti-inflammatory immune responses in mouse islet allograft rejection. AB - Recently, pancreatic islet transplantation has been shown to be a viable option for the treatment of type 1 diabetes mellitus. However, immune destruction becomes the major impediment to the clinical application of islet transplantation. Here, we evaluated changes affecting multiple types of immune cells and cytokines in allogeneic islet transplantation immunity after the administration of B10 cells alone and explored the regulatory mechanisms of B10 cells in T cell-mediated allograft rejection. In vitro assays, B10 cells significantly decreased the proliferative capacity of CD4+CD25- T cells (13.75%+/ 0.96% vs. 32.76%+/-0.81%) while enhancing the proliferation of regulatory T cells (Tregs) (26.60%+/-1.14% vs. 21.52%+/-0.81%). Furthermore, after the administration of B10 cells in vivo, the frequencies of IL-10+ B cells and Tregs of islet transplant recipients were increased by the CD19+CD5+CD1dhi B cells, and the CD4+/CD8+ and IFN-gamma+/IL-17+ ratios were decreased. Serum IL-10 levels were up-regulated, while IFN-gamma levels were down-regulated. Grafts from 1 to 5*106 B10 cell-treated recipients exhibited a reduced level of insulitis compared with the untreated controls, although the differences of graft survival times were not statistically significant. In general, in mouse islet allograft rejection, B10 cells may alleviate T cell-mediated immune responses by promoting Treg-cell development and inhibiting Th1 cells activation, via an IL-10-dependent pathway. Development of B10 cell-targeted therapy may be benefit for modulating immune response and provide insight into the signals involved the induction of islet allograft tolerance. PMID- 27667760 TI - The assessment of abdominal and multifidus muscles and their role in physical function in older adults: a systematic review. AB - BACKGROUND: Age-related changes in the trunk (abdominal and lumbar multifidus) muscles and their impact on physical function of older adults are not clearly understood. OBJECTIVES: To systematically summarise studies of these trunk muscles in older adults. DATA SOURCES: Cochrane Library, Pubmed, EMBASE and CINAHL were searched using terms for abdominal and MF muscles and measurement methods. STUDY SELECTION: Two reviewers independently assessed studies and included those reporting measurements of abdominal muscles and/or MF by ultrasound, computed tomography, magnetic resonance imaging or electromyography of adults aged >=50 years. DATA SYNTHESIS: A best evidence synthesis was performed. RESULTS: Best evidence synthesis revealed limited evidence for detrimental effects of ageing or spinal conditions on trunk muscles, and conflicting evidence for decreased physical activity or stroke having detrimental effects on trunk muscles. Thicknesses of rectus abdominis, internal oblique and external oblique muscles were 36% to 48% smaller for older than younger adults. Muscle quality was poorer among people with moderate-extreme low back pain and predicted physical function outcomes. LIMITATIONS: Study heterogeneity precluded meta-analysis. CONCLUSION: Overall, the evidence base in older people has significant limitations, so the role of physiotherapy interventions aimed at these muscles remains unclear. The results point to areas in which further research could lead to clinically useful outcomes. These include determining the role of the trunk muscles in the physical function of older adults and disease; developing and testing rehabilitation programmes for older people with spinal conditions and lower back pain; and identifying modifiable factors that could mitigate age-related changes. PMID- 27667761 TI - OTSC(r) system for the treatment of gastrointestinal perforations. PMID- 27667763 TI - Reply. PMID- 27667762 TI - Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome. AB - BACKGROUND: Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment. OBJECTIVE: The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years. STUDY DESIGN: A total of 26 prematurely born intrauterine growth restriction infants (birthweight <10th centile for gestational age), 22 prematurely born but adequate for gestational age controls, and 26 term adequate-for-gestational-age infants underwent brain magnetic resonance imaging and magnetic resonance spectroscopy at 1 year of age during natural sleep, on a 3 Tesla scanner. All brain T1-weighted and diffusion-weighted images were acquired along with short echo time single-voxel proton spectra from the frontal lobe. Magnetic resonance imaging/magnetic resonance spectroscopy data were processed to derive structural, biophysical, and metabolic information, respectively. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales 3rd edition, assessing cognitive, language, motor, socioemotional, and adaptive behavior. RESULTS: Prematurely born intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset. CONCLUSIONS: Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which correlate with brain structural and biophysical parameters and neurodevelopmental outcome. Our results suggest altered neurodevelopmental trajectories in preterm intrauterine growth restriction and adequate-for gestational-age infants, compared with term adequate-for-gestational-age infants, which require further characterization. PMID- 27667764 TI - Reducing maternal health disparities: the rural context. PMID- 27667765 TI - Reply. PMID- 27667766 TI - Efficacy of oral valacyclovir in cytomegalovirus-infected fetuses. PMID- 27667767 TI - Longitudinal fetal heart rate changes are not generally disregarded but should be supplemented by meaningful categorization of decelerations. PMID- 27667768 TI - Safety assessment and attenuation of cisplatin induced nephrotoxicity by tuberous roots of Boerhaavia diffusa. AB - Cisplatin (Cis-diaminedichloroplatinum II) is a chemotherapeutic agent having well documented adverse effect as nephrotoxicity. This study was designed to evaluate the nephroprotective role of Boerhaavia diffusa in cisplatin-induced acute kidney injury. Wistar rats (n = 6) were allocated into six groups constituting normal control, cisplatin-induced, Boerhaavia diffusa root extract in doses 50, 100 and 200 mg/kg and Boerhaavia diffusa per se group, administered orally for a period of ten days. Intraperitoneal injection of cisplatin was administered on day 7, to all groups except normal control and Boerhaavia diffusa per se group. On day 10, cisplatin resulted in substantial nephrotoxicity in Wistar rats with significant (p < 0.001) elevation in serum creatinine and blood urea nitrogen, decline in the concentrations of reduced glutathione and superoxide dismutase, elevation in TNF-alpha level in renal tissues. Boerhaavia diffusa at a dose of 200 mg/kg body weight significantly (p < 0.001) ameliorates increased in serum creatinine, blood urea nitrogen, oxidative stress and inflammatory markers. In parallel to this, it also exhibits antiapoptotic activity through the reduction of active caspase-3 expression in kidneys. Findings indicate that Boerhaavia diffusa is effective in mitigating cisplatin induced nephrotoxicity and thus, for this the acute and sub-acute toxicity studies conducted to evaluate the safety profile of Boerhaavia diffusa. The no observed adverse effect level (NOAEL) of tuberous roots of Boerhaavia diffusa root extract was 1000 mg/kg. PMID- 27667769 TI - Patterns of perioperative thoracic fluid indices changes in liver transplantation with or without postoperative acute lung injury. AB - BACKGROUND/PURPOSE: Postoperative acute lung injury (ALI) after liver transplantation is clinically relevant and common. The perioperative thoracic fluid indices changes as well as the association with ALI in liver transplantation have not been thoroughly investigated. METHODS: A total of 52 consecutive adult recipients for elective living donor liver transplantation were enrolled. Each recipient received the same perioperative care plan. Thoracic fluid indices, including the cardiac index, intrathoracic blood volume index (ITBVI), extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI), were obtained at seven time points (pretransplantation, anhepatic phase, 30 minutes after reperfusion, 2 hours after reperfusion, and postoperative days 1-3) using the pulse contour cardiac output system. The indices of those who developed ALI (PaO2/FiO2 < 300 mmHg with lung infiltrates on chest X-ray) were compared with the indices of those who did not. RESULTS: Recipients who developed postoperative ALI had longer mechanical ventilation duration and had a higher model for end-stage liver disease score, required more platelet transfusion, and were higher in pretransplant EVLWI and PVPI level. During the anhepatic phase, ITBVI, central venous pressure, cardiac index, and EVLWI decreased and PVPI increased. After transplantation, ITBVI increased above pretransplant status, while EVLWI and PVPI were comparable in both groups. CONCLUSION: Recipients who did or did not develop ALI after liver transplantation had a longer mechanical ventilation duration and showed different patterns of perioperative thoracic fluid indices, especially in the pretransplant status of PVPI level. Knowledge of these perioperative changes may provide clinicians with helpful information to make postoperative care choices. PMID- 27667770 TI - Novel celecoxib analogues inhibit glial production of prostaglandin E2, nitric oxide, and oxygen radicals reverting the neuroinflammatory responses induced by misfolded prion protein fragment 90-231 or lipopolysaccharide. AB - We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3 thiazolidin-4-one analogues. As experimental models, we used the immortalized microglial cell line N9, rat purified microglial primary cultures, and mixed cultures of astrocytes and microglia. Microglia activation in response to PrP90 231 or LPS was characterized by growth arrest, morphology changes and the production of reactive oxygen species (ROS). Moreover, PrP90-231 treatment caused the overexpression of the inducible nitric oxide synthase (iNOS) and COX-2, with the consequent nitric oxide (NO), and prostaglandin E2 (PGE2) accumulation. These effects were challenged by different celecoxib analogues, among which Q22 (3-[4 (sulfamoyl)phenyl]-2-(4-tolyl)thiazolidin-4-one) inhibited microglia activation more efficiently than celecoxib, lowering both iNOS and COX-2 activity and reducing ROS release. During neurodegenerative diseases, neuroinflammation induced by amyloidogenic peptides causes the activation of both astrocytes and microglia with these cell populations mutually regulating each other. Thus the effects of PrP90-231 and LPS were also studied on mixed glial cultures containing astrocytes and microglia. PrP90-231 treatment elicited different responses in the co-cultures induced astrocyte proliferation and microglia growth arrest, resulting in a differential ability to release proinflammatory molecules with the production of NO and ROS mainly attributable on microglia, while COX-2 expression was induced also in astrocytes. Q22 effects on both NO and PGE2 secretion were more significant in the mixed glial cultures than in purified microglia, demonstrating Q22 ability to revert the functional interaction between astrocytes and microglia. These results demonstrate that Q22 is a powerful drug able to revert glial neuroinflammatory responses and might represent a lead to explore the chemical space around celecoxib frameworks to design even more effective agents, paving the way to novel approaches to contrast the neuroinflammation dependent toxicity. PMID- 27667772 TI - T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection. AB - Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself. PMID- 27667773 TI - An Analytical Comparison of Dako 28-8 PharmDx Assay and an E1L3N Laboratory Developed Test in the Immunohistochemical Detection of Programmed Death-Ligand 1. AB - AIM: Nivolumab, a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has activity in melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and Hodgkin lymphoma. Nivolumab is approved in the USA and EU for advanced melanoma, NSCLC, and RCC, and relapsed Hodgkin lymphoma in the USA. Programmed death-ligand 1 (PD-L1), a PD-1 ligand, is expressed on mononuclear leukocytes, myeloid cells, and tumor cells. PD-L1 is being investigated as a potential biomarker to predict the association of tumor PD-L1 expression with nivolumab efficacy. METHODS: Bristol-Myers Squibb and Dako previously reported on an automated PD-L1 immunohistochemical (IHC) assay that detects cell surface PD-L1 in formalin-fixed, paraffin-embedded, human tumor tissue specimens using Dako's Autostainer Link 48. The primary antibody for this assay is a rabbit monoclonal antihuman PD-L1 antibody, clone 28-8. Another rabbit monoclonal antihuman PD-L1 antibody, clone E1L3N, was compared with 28-8 for specificity and sensitivity using an identical detection method followed by vendor-recommended detection methods. RESULTS: Using PD-L1 null clones of L2987 and ES-2 tumor cell lines, both antibodies were specific for detection of PD-L1 on the plasma membrane, although E1L3N also stained cytoplasm in ES-2 knockout cells. Using the identical method, E1L3N was slightly more sensitive than 28-8 based on staining intensities. Using manufacturer-recommended detection methods and predefined scoring criteria for plasma membrane staining of tumor and immune cells, 28-8 demonstrated significantly improved detection compared with E1L3N. CONCLUSIONS: Epitope retrieval and highly sensitive detection reagents are key determinants in IHC detection of PD-L1. PMID- 27667775 TI - Facile One-Step Route for the Development of in Situ Cocatalyst-Modified Ti3+ Self-Doped TiO2 for Improved Visible-Light Photocatalytic Activity. AB - Development of visible-light-driven photocatalysts by employing a relatively simple, efficient, and cost-effective one-step process is essential for commercial applications. Herein, we report for the first time the synthesis of in situ Cu-ion modified Ti3+ self-doped rutile TiO2 by such a facile one-step solution precursor plasma spray (SPPS) process using a water-soluble titanium precursor. In the SPPS process, Ti3+ self-doping on Ti4+ of rutile TiO2 is found to take place because of electron transfer from the created oxygen vacancies to Ti4+-ions. In situ Cu modification of the above Ti3+ self-doped rutile TiO2 by additionally introducing a Cu solution into plasma plume is also demonstrated. While the Ti3+ self-doping induces broad absorption in the visible-light region, the addition of Cu ion leads to even broader absorption in the visible region owing to resulting synergistic properties. The above materials were evaluated for various self-cleaning photocatalytic applications under visible-light illumination. Cu-ion modified Ti3+ self-doped rutile TiO2 is noted to exhibit a remarkably enhanced visible-light activity in comparison with Ti3+ self-doped rutile TiO2, with the latter itself outperforming commercial TiO2 photocatalysts, thereby suggesting the suitability of the material for indoor applications. The broad visible-light absorption by Ti3+ self-doping, the holes with strong oxidation power generated in the valence band, and electrons in Ti3+ isolated states that are effectively separated into the high reductive sites of Cu ions upon visible-light irradiation, accounts for improved photocatalytic activity. Moreover, the synthesis process (SPPS) provides a valuable alternative to orthodox multistep processes for the preparation of such visible-light-driven photocatalysts. PMID- 27667774 TI - Glucosamine exposure reduces proteoglycan synthesis in primary human endothelial cells in vitro. AB - PURPOSE: Glucosamine (GlcN) supplements are promoted for medical reasons, for example, for patients with arthritis and other joint-related diseases. Oral intake of GlcN is followed by uptake in the intestine, transport in the circulation and thereafter delivery to chondrocytes. Here, it is postulated to have an effect on synthesis and turnover of extracellular matrix constituents expressed by these cells. Following uptake in the intestine, serum levels are transiently increased, and the endothelium is exposed to increased levels of GlcN. We investigated the possible effects of GlcN on synthesis of proteoglycans (PGs), an important matrix component, in primary human endothelial cells. METHODS: Primary human endothelial cells were cultured in vitro in medium with 5 mM glucose and 0-10 mM GlcN. PGs were recovered and analysed by western blotting, or by SDS-PAGE, gel chromatography or ion-exchange chromatography of (35)S-PGs after (35)S-sulphate labelling of the cells. RESULTS: The synthesis and secretion of (35)S-PGs from cultured endothelial cells were reduced in a dose- and time dependent manner after exposure to GlcN. PGs are substituted with sulphated glycosaminoglycan (GAG) chains, vital for PG function. The reduction in (35)S-PGs was not related to an effect on GAG chain length, number or sulphation, but rather to the total expression of PGs. CONCLUSION: Exposure of endothelial cells to GlcN leads to a general decrease in (35)S-PG synthesis. These results suggest that exposure to high levels of GlcN can lead to decreased matrix synthesis, contrary to what has been claimed by supporters of such supplements. PMID- 27667776 TI - Seeing What You Want to See: How Imprecise Uncertainty Ranges Enhance Motivated Reasoning. AB - In this article, we consider a novel criterion for evaluating representations of uncertainty ranges, namely, the extent to which a representation enhances motivated reasoning. In two studies, we show that perceptions of the distribution underlying ambiguous numerical ranges are affected by the motivations and worldviews of end users. This motivated reasoning effect remained after controlling for objective numeracy and fluid intelligence but was attenuated when the correct interpretation was made clear. We suggest that analysts and communicators explicitly consider the potential for motivated evaluation when evaluating uncertainty displays. PMID- 27667771 TI - Understanding metabolism with flux analysis: From theory to application. AB - Quantitative and qualitative knowledge of metabolic rates (i.e. fluxes) over a metabolic network and in specific cellular compartments gives insights into the regulation of metabolism and helps to understand the contribution of metabolic alterations to pathology. In this review we introduce methodology to resolve metabolic fluxes from stable isotope labeling and relevant techniques in model development, model simplification, flux uncertainty analysis and experimental design that together is termed metabolic flux analysis. Finally we discuss applications using metabolic flux analysis to elucidate mechanisms pertinent to tumor cell metabolism. We hope that this review gives the readers a brief introduction of how flux analysis is conducted, how technical issues related to it are addressed, and how its application has contributed to our knowledge of tumor cell metabolism. PMID- 27667777 TI - Networks underlying trait impulsivity: Evidence from voxel-based lesion-symptom mapping. AB - Impulsivity is considered a multidimensional construct that encompasses a range of behaviors, including poor impulse control, premature decision-making, and the inability to delay gratification. In order to determine the extent to which impulsivity and its components share a common network, a voxel-based lesion symptom mapping (VLSM) analysis was performed in a large sample of patients (N = 131) with focal, penetrating traumatic brain injuries (pTBI). Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), a standard self-report measure that allows for unique estimates of global impulsivity and its factor analysis-derived components (e.g., "motor impulsivity"). Heightened global impulsivity was associated with damage to multiple areas in bilateral prefrontal cortex (PFC), left superior, middle and inferior temporal gyrus, and left hippocampus. Moreover, a cluster was identified within the left PFC associated specifically with motor impulsivity (defined as "acting without thinking"). The results were consistent with the existing literature on bilateral prefrontal cortical involvement in behavioral impulsivity, but also provided new evidence for a more complex neuroanatomical representation of this construct, characterized by left-lateralized temporal and hippocampal involvement, as well as a left-lateralized prefrontal network specifically associated with motor impulsivity. Hum Brain Mapp 38:656-665, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27667778 TI - Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures? AB - Thermal performance curves (TPCs), which quantify how an ectotherm's body temperature (Tb ) affects its performance or fitness, are often used in an attempt to predict organismal responses to climate change. Here, we examine the key - but often biologically unreasonable - assumptions underlying this approach; for example, that physiology and thermal regimes are invariant over ontogeny, space and time, and also that TPCs are independent of previously experienced Tb. We show how a critical consideration of these assumptions can lead to biologically useful hypotheses and experimental designs. For example, rather than assuming that TPCs are fixed during ontogeny, one can measure TPCs for each major life stage and incorporate these into stage-specific ecological models to reveal the life stage most likely to be vulnerable to climate change. Our overall goal is to explicitly examine the assumptions underlying the integration of TPCs with Tb , to develop a framework within which empiricists can place their work within these limitations, and to facilitate the application of thermal physiology to understanding the biological implications of climate change. PMID- 27667779 TI - Comparison of functional outcomes between laparoscopic radical prostatectomy and robot-assisted laparoscopic radical prostatectomy: a propensity score-matched comparison study. AB - AIM: To compare the functional outcomes after laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RARP). METHODS: Between September 2008 and January 2016, 712 patients underwent radical prostatectomy (RP; 614 LRP and 98 RARP). Recovery of incontinence was evaluated through a 24-h pad test. Urinary and erectile function was evaluated using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5. Follow-up interval was 1, 3, 6 and 12 months after the surgery. The propensity score matching was used to balance the preoperative characteristics. RESULTS: The recovery of incontinence was similar to the two groups at 6 and 12 months after the surgery. However, patients underwent RARP restored the continence sooner than those in the LRP group in 1 and 3 months after the surgery (P < 0.001 and 0.001). For the multivariable analysis, the type of RP procedure was a uniquely meaningful contributing factor (P = 0.001, HR = 1.925; 95% CI, 1.299-2.851). In the case of urinary function, the RARP groups showed a better IPSS score than LRP groups at the 1-, 3- and 6-month visits, respectively (P = 0.008, 0.026, 0.001), and the RARP groups early improved compared with LRP groups at the 3-month visit in the case of erectile function (P = 0.018). CONCLUSION: The RARP tended toward getting back the urinary continence earlier than the LRP. In addition, urinary and erectile function recovered more quickly in the RARP group than in the LRP group. PMID- 27667780 TI - Use of benzodiazepine and risk of cancer: A meta-analysis of observational studies. AB - Several observational epidemiological studies have reported inconsistent results on the association between the use of benzodiazepine and the risk of cancer. We investigated the association by using a meta-analysis. We searched PubMed, EMBASE, and the bibliographies of relevant articles to locate additional publications in January 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. Of 796 articles meeting our initial criteria, a total of 22 observational epidemiological studies with 18 case-control studies and 4 cohort studies were included in the final analysis. Benzodiazepine use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.19; 95% confidence interval 1.16-1.21) in a random-effects meta-analysis of all studies. Subgroup meta-analyses by various factors such as study design, type of case control study, study region, and methodological quality of study showed consistent findings. Also, a significant dose-response relationship was observed between the use of benzodiazepine and the risk of cancer (p for trend <0.01). The current meta-analysis of observational epidemiological studies suggests that benzodiazepine use is associated with an increased risk of cancer. PMID- 27667781 TI - Diffusion in hierarchical systems: A simulation study in models of healthy and diseased muscle tissue. AB - PURPOSE: To investigate the sensitivity of diffusion-MR signal to microstructural change in muscle tissue associated with pathology, and recommend optimal acquisition parameters. METHODS: We employ Monte-Carlo simulation of diffusing spins in hierarchical tissue to generate synthetic diffusion-weighted signal curves over a wide range of scan parameters. Curves are analyzed using entropy-a measure of curve complexity. Entropy change between a baseline and various microstructural scenarios is investigated. We find acquisitions that optimize entropy difference in each scenario. RESULTS: Permeability changes have a large effect on the diffusion-weighted signal curve. Muscle fiber atrophy is also important, although differentiating between mechanisms is challenging. Several acquisitions over a range of diffusion times is optimal for imaging microstructural change in muscle tissue. Sensitivity to permeability is optimized for high gradient strengths, but sensitivity to other scenarios is optimal at other values. CONCLUSIONS: The diffusion-attenuated signal is sensitive to the microstructural changes, but the changes are subtle. Taking full advantage of the changes to the overall curve requires a set of acquisitions over a range of diffusion times. Permeability causes the largest changes, but even the very subtle changes associated with fiber radius distribution change the curves more than noise alone. Magn Reson Med 78:1187-1198, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27667783 TI - Comparison of Feline Brain Anatomy in 0.25 and 3 Tesla Magnetic Resonance Images. AB - The intention of the comparison of both low and high field was to examine which anatomical brain structures of cats were visible on low field images, as in clinical veterinary practice, 3 Tesla (T) magnets were of limited availability. The research was performed on 20 European short-haired male and female cats, aged 1-3 years, with body weight of 2-4 kg. 0.25 T magnetic resonance images of neurocranium were acquired in all using T2-weighted fast spin echo sequences with repetition time (TR) of 4010 ms and echo time (TE) of 90 ms in dorsal and transverse plane, and T2-weighted fast spine echo sequences with TR of 4290 ms and TE of 120 ms in sagittal plane. Based on a detailed catalogue of feline brain structures visible at 3 T in previously published studies, it was examined which structures were visible on low field images. Anatomic structures were identified and compared to assess the reliability of diagnoses made based on low-field magnetic resonance imaging. In low-field scans, 92 structures were identified. Elements of auditory, visual, motor pathways, hippocampus and cerebral ventricular system were distinguished. Low-field as well as high-field magnetic resonance imaging support the identification of local tissue lesions, metastasis, focal ischaemia and haemorrhage, disorders associated with ventricular system dilation and hydrocephalus. It also produced accurate images of the hippocampus, which contributes to reliable diagnoses of various forms of epilepsy in cats. Due to technical limitations, a low-field scanner is unlikely to visualize microtraumas, local inflammations, small haematomas or metastatic tumours. PMID- 27667784 TI - Treatment of eosinophilic otitis media with pegylated interferon-alpha 2a and 2b. AB - OBJECTIVE/HYPOTHESIS: Eosinophilic otitis media (EOM) is a variant of chronic otitis media that is characterized by the development of thick mucoid middle ear effusion, adult onset bronchial asthma, sinonasal polyposis, and aspirin sensitivity. EOM is typically refractory to corticosteroid therapy and surgical intervention. Pegylated interferon (PEG-IFN) has effectively treated hypereosinophilic syndrome in clinical trials; however, the efficacy of this medication for EOM treatment remains undefined. STUDY DESIGN: Retrospective, case series, tertiary academic center. METHODS: A retrospective chart review was performed on EOM patients from 2008-2014. A total of 32 patients met the clinical criteria for EOM according to established diagnostic guidelines. Outcomes of all patients with severe, refractory EOM who initiated PEG-IFN therapy are reported. RESULTS: Eight patients were treated with pegylated interferon-alpha 2a or 2b for refractory EOM. Half of the patients had significant side effects with interferon treatment. Three of these were able to continue at a reduced dosage without side effect reoccurrence, and one patient stopped the medication permanently. Four of eight (50%) patients had a complete clinical response with total resolution of otorrhea and normalization of middle ear mucosa, and were able to discontinue corticosteroid treatment. Two patients attempted to stop PEG-IFN therapy after prolonged symptom remission and had recurrent otorrhea. Both patients had symptom resolution after PEG-IFN reinitiation. CONCLUSIONS: These data demonstrate that pegylated interferon-alpha 2a and 2b therapy may benefit patients with severe, refractory EOM. Further larger studies with long-term follow-up are required to validate these early but promising results. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1208-1216, 2017. PMID- 27667785 TI - Successful laparoscopic ligation for massive chylous ascites after rectal cancer surgery. AB - A 53-year-old man was readmitted with abdominal distention 2 weeks after undergoing laparoscopic low anterior resection with para-aortic lymphadenectomy for advanced rectal cancer (T4aN1M0, Stage IIIb). Ultrasound revealed massive ascites, and paracentesis revealed chylous fluid with a markedly elevated triglyceride level (1762 mg/dL). Despite conservative management, the fistula remained on postoperative day 120. On percutaneous lymphangiography, the chylous leakage point was clearly visualized at the para-aortic site, and surgical intervention was planned. The abdominal cavity was carefully explored with laparoscopy, and the lymphatic leakage point was detected at the site of previous lymphadenectomy. Leakage was stopped with direct suture ligation and fibrin glue, and the patient was discharged 2 weeks later with no recurrence of the chylous fistula. Surgical intervention can be effective in select patients with a major chylous fistula that persists despite conservative therapy. When the leakage point is localized and detectable on percutaneous lymphangiography, the laparoscopic approach may be feasible. PMID- 27667782 TI - Interferon gamma modulation of disease manifestation and the local antibody response to alphavirus encephalomyelitis. AB - Infection of mice with Sindbis virus (SINV) produces encephalomyelitis and provides a model for examination of the central nervous system (CNS) immune response to alphavirus infection. Clearance of infectious virus is accomplished through a cooperative effort between SINV-specific antibody and IFN-gamma, but the regulatory interactions are poorly understood. To determine the effects of IFN-gamma on clinical disease and the antiviral immune response, C57BL/6 mice lacking IFN-gamma (Ifng-/-) or IFN-gamma receptor (Ifngr1-/-) were studied in comparison to WT mice. Maximum production of Ifng mRNA and IFN-gamma protein in the CNS of WT and Ifngr1-/- mice occurred 5-7 days after infection, with higher levels of IFN-gamma in Ifngr1-/- mice. Onset of clinical disease was earlier in mice with impaired IFN-gamma signalling, although Ifngr1-/- mice recovered more rapidly. Ifng-/- and Ifngr1-/- mice maintained body weight better than WT mice, associated with better food intake and lower brain levels of inflammatory cytokines. Clearance of infectious virus from the spinal cords was slower, and CNS, but not serum, levels of SINV-specific IgM, IgG2a and IgG2b were lower in Ifngr1-/- and Ifng-/- mice compared to WT mice. Decreased CNS antiviral antibody was associated with lower expression of mRNAs for B-cell attracting chemokines CXCL9, CXCL10 and CXCL13 and fewer B cells in the CNS. Therefore, IFN-gamma signalling increases levels of CNS pro-inflammatory cytokines, leading to clinical disease, but synergistically clears virus with SINV-specific antibody at least in part by increasing chemokine production important for infiltration of antibody-secreting B cells into the CNS. PMID- 27667786 TI - Treatment of 100 chronic thalassemic leg wounds by plasma-rich platelets. AB - OBJECTIVE: Thalassemia is a heterogeneous group of congenital hemoglobinopathies caused by mutations in the globin gene complex that result in an unbalanced globin synthesis. Unmatched globin chains bind to the cytosolic surface of red blood cell membrane where they cause oxidative damage that might in part be responsible for membrane weakness. The deformability of red blood cells and hypercoagulable state in thalassemic patients have been incriminated in leg ulcer formation, as this might cause ischemia to the skin and consequently friability and ulceration. METHODS: Platelet-rich plasma (PRP) gel is considered an advanced wound therapy for chronic and acute wounds. PRP gel consists of cytokines, growth factors, chemokines, and a fibrin scaffold derived from a patient's blood. In this study, we treated 100 thalassemic leg wounds using PRP. RESULTS: There was wound size reduction in patients after 4 weeks of treatment. In wounds with 2-3.5 cm2 surface area, complete closure happened after 12.5 weeks, 5-12 cm2 wounds completely closed after 13.2 weeks, and finally, 4.5-6 cm2 wounds healed completely after 14 weeks. None of the wounds reopened after 8 months of monitoring. CONCLUSION: This study will help extrapolation of the use of PRP for at least thalassemic leg wound treatment. PMID- 27667788 TI - Sequential Barium-Catalysed N-H/H-Si Dehydrogenative Cross-Couplings: Cyclodisilazanes versus Linear Oligosilazanes. AB - Starting from Ph3 SiH, the barium precatalyst Ba[CH(SiMe3 )2 ]2 ?(THF)3 was used to produce the disilazane Ph3 SiN(Bn)SiPh2 NHBn (4) by sequential N-H/H-Si dehydrogenative couplings with BnNH2 and Ph2 SiH2 . Substrate scope was extended to other amines and hydrosilanes. This smooth protocol gives quantitative yields and full chemoselectivity. Compound 4 and the intermediates Ph3 SiNHBn and Ph3 SiN(Bn)SiHPh2 were structurally characterised. Further attempts at chain extension by dehydrocoupling of Ph2 SiH2 with 4 instead resulted in cyclisation of this compound, forming the cyclodisilazane c-(Ph2 Si-NBn)2 (5) which was crystallographically authenticated. The ring-closure mechanism leading to 5 upon release of C6 H6 was determined by complementary experimental and theoretical (DFT) investigations. Ba[CH(SiMe3 )2 ]2 ?(THF)3 and 4 react to afford the reactive Ba{N(Bn)SiPh2 N(Bn)SiPh3 }2 , which was characterised in situ by NMR spectroscopy. Next, in a stepwise process, intramolecular nucleophilic attack of the metal-bound amide on the terminal silicon atom generates a five-coordinate silicate. It is followed by turnover-limiting beta-C6 H5 transfer to barium; this releases 5 and forms a transient [Ba]-Ph species, which undergoes aminolysis to regenerate [Ba]-N(Bn)SiPh2 N(Bn)SiPh3 . DFT computations reveal that the irreversible production of 5 through such a stepwise ring-closure mechanism is much more kinetically facile (DeltaG? =26.2 kcal mol-1 ) than an alternative sigma-metathesis pathway (DeltaG? =48.2 kcal mol-1 ). PMID- 27667789 TI - Bacteriological and histopathological study of farmed rainbow trout, Oncorhynchus mykiss, in Peru. PMID- 27667787 TI - Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4+ T cells partly via transforming growth factor-beta1. AB - Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4+ T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-beta1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC. By inhibiting TGF-beta1 signalling we demonstrate that tolDC regulate CD4+ T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF-betaRII on CD4+ T cells from RA patients and healthy controls, RA patient CD4+ T cells are measurably less responsive to TGF-beta1 than healthy control CD4+ T cells [reduced TGF-beta-induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)-gamma secretion]. However, CD4+ T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF-beta1-dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA. PMID- 27667790 TI - cMapper: gene-centric connectivity mapper for EBI-RDF platform. AB - MOTIVATION: In this era of biological big data, data integration has become a common task and a challenge for biologists. The Resource Description Framework (RDF) was developed to enable interoperability of heterogeneous datasets. The EBI RDF platform enables an efficient data integration of six independent biological databases using RDF technologies and shared ontologies. However, to take advantage of this platform, biologists need to be familiar with RDF technologies and SPARQL query language. To overcome this practical limitation of the EBI-RDF platform, we developed cMapper, a web-based tool that enables biologists to search the EBI-RDF databases in a gene-centric manner without a thorough knowledge of RDF and SPARQL. RESULTS: cMapper allows biologists to search data entities in the EBI-RDF platform that are connected to genes or small molecules of interest in multiple biological contexts. The input to cMapper consists of a set of genes or small molecules, and the output are data entities in six independent EBI-RDF databases connected with the given genes or small molecules in the user's query. cMapper provides output to users in the form of a graph in which nodes represent data entities and the edges represent connections between data entities and inputted set of genes or small molecules. Furthermore, users can apply filters based on database, taxonomy, organ and pathways in order to focus on a core connectivity graph of their interest. Data entities from multiple databases are differentiated based on background colors. cMapper also enables users to investigate shared connections between genes or small molecules of interest. Users can view the output graph on a web browser or download it in either GraphML or JSON formats. AVAILABILITY AND IMPLEMENTATION: cMapper is available as a web application with an integrated MySQL database. The web application was developed using Java and deployed on Tomcat server. We developed the user interface using HTML5, JQuery and the Cytoscape Graph API. cMapper can be accessed at http://cmapper.ewostech.net Readers can download the development manual from the website http://cmapper.ewostech.net/docs/cMapperDocumentation.pdf. Source Code is available at https://github.com/muhammadshoaib/cmapperContact:smahn@gachon.ac.krSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27667791 TI - LongISLND: in silico sequencing of lengthy and noisy datatypes. AB - : LongISLND is a software package designed to simulate sequencing data according to the characteristics of third generation, single-molecule sequencing technologies. The general software architecture is easily extendable, as demonstrated by the emulation of Pacific Biosciences (PacBio) multi-pass sequencing with P5 and P6 chemistries, producing data in FASTQ, H5, and the latest PacBio BAM format. We demonstrate its utility by downstream processing with consensus building and variant calling. AVAILABILITY AND IMPLEMENTATION: LongISLND is implemented in Java and available at http://bioinform.github.io/longislnd CONTACT: hugo.lam@roche.comSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27667792 TI - Detecting subnetwork-level dynamic correlations. AB - MOTIVATION: The biological regulatory system is highly dynamic. The correlations between many functionally related genes change over different biological conditions. Finding dynamic relations on the existing biological network may reveal important regulatory mechanisms. Currently no method is available to detect subnetwork-level dynamic correlations systematically on the genome-scale network. Two major issues hampered the development. The first is gene expression profiling data usually do not contain time course measurements to facilitate the analysis of dynamic relations, which can be partially addressed by using certain genes as indicators of biological conditions. Secondly, it is unclear how to effectively delineate subnetworks, and define dynamic relations between them. RESULTS: Here we propose a new method named LANDD (Liquid Association for Network Dynamics Detection) to find subnetworks that show substantial dynamic correlations, as defined by subnetwork A is concentrated with Liquid Association scouting genes for subnetwork B. The method produces easily interpretable results because of its focus on subnetworks that tend to comprise functionally related genes. Also, the collective behaviour of genes in a subnetwork is a much more reliable indicator of underlying biological conditions compared to using single genes as indicators. We conducted extensive simulations to validate the method's ability to detect subnetwork-level dynamic correlations. Using a real gene expression dataset and the human protein-protein interaction network, we demonstrate the method links subnetworks of distinct biological processes, with both confirmed relations and plausible new functional implications. We also found signal transduction pathways tend to show extensive dynamic relations with other functional groups. AVAILABILITY AND IMPLEMENTATION: The R package is available at https://cran.r-project.org/web/packages/LANDD CONTACTS: yunba@pcom.edu, jwlu33@hotmail.com or tianwei.yu@emory.eduSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27667793 TI - LAMSA: fast split read alignment with long approximate matches. AB - MOTIVATION: Read length is continuously increasing with the development of novel high-throughput sequencing technologies, which has enormous potentials on cutting edge genomic studies. However, longer reads could more frequently span the breakpoints of structural variants (SVs) than that of shorter reads. This may greatly influence read alignment, since most state-of-the-art aligners are designed for handling relatively small variants in a co-linear alignment framework. Meanwhile, long read alignment is still not as efficient as that of short reads, which could be also a bottleneck for the upcoming wide application. RESULTS: We propose long approximate matches-based split aligner (LAMSA), a novel split read alignment approach. It takes the advantage of the rareness of SVs to implement a specifically designed two-step strategy. That is, LAMSA initially splits the read into relatively long fragments and co-linearly align them to solve the small variations or sequencing errors, and mitigate the effect of repeats. The alignments of the fragments are then used for implementing a sparse dynamic programming-based split alignment approach to handle the large or non-co linear variants. We benchmarked LAMSA with simulated and real datasets having various read lengths and sequencing error rates, the results demonstrate that it is substantially faster than the state-of-the-art long read aligners; meanwhile, it also has good ability to handle various categories of SVs. AVAILABILITY AND IMPLEMENTATION: LAMSA is available at https://github.com/hitbc/LAMSA CONTACT: Ydwang@hit.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online. PMID- 27667794 TI - Site of metabolism prediction for oxidation reactions mediated by oxidoreductases based on chemical bond. AB - Motivation: The metabolites of exogenous and endogenous compounds play a pivotal role in the domain of metabolism research. However, they are still unclear for most chemicals in our environment. The in silico methods for predicting the site of metabolism (SOM) are considered to be efficient and low-cost in SOM discovery. However, many in silico methods are focused on metabolism processes catalyzed by several specified Cytochromes P450s, and only apply to substrates with special skeleton. A SOM prediction model always deserves more attention, which demands no special requirements to structures of substrates and applies to more metabolic enzymes. Results: By incorporating the use of hybrid feature selection techniques (CHI, IG, GR, Relief) and multiple classification procedures (KStar, BN, IBK, J48, RF, SVM, AdaBoostM1, Bagging), SOM prediction models for six oxidation reactions mediated by oxidoreductases were established by the integration of enzyme data and chemical bond information. The advantage of the method is the introduction of unlabeled SOM. We defined the SOM which not reported in the literature as unlabeled SOM, where negative SOM was filtered. Consequently, for each type of reaction, a series of SOM prediction models were built based on information about metabolism of 1237 heterogeneous chemicals. Then optimal models were attained through comparisons among these models. Finally, independent test set was used to validate optimal models. It demonstrated that all models gave accuracies above 0.90. For receiver operating characteristic analysis, the area under curve values of all these models over 0.906. The results suggested that these models showed good predicting power. Availability and implementation: All the models will be available when contact with wangyun@bucm.edu.cn. Contacts: wangyun@bucm.edu.cn or yjqiao@yahoo.com. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 27667796 TI - Case of squamous cell carcinoma showing delayed metastasis and histologically exhibiting alterations of the surrounding immune cell populations along with the tumor invasion: Expression of monocyte chemotactic protein-1 in deeply invaded tumor cells and interleukin-6 in surrounding histiocytes. PMID- 27667797 TI - Glycemic control and safety in Chinese patients with type 2 diabetes mellitus who switched from premixed insulin to insulin glargine plus oral antidiabetics: a large, prospective, observational study. AB - In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18-75 years) who had received premixed insulin +/- OADs for >=3 months with glycated hemoglobin (HbA1c) <= 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2-hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% +/- 1.2% at week 1 to 7.0% +/- 1.0% at week 16; P < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2-hour PPG decreased significantly (-1.4 +/- 2.2 and -2.1 +/- 3.9 mmol/L, respectively; both P < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels. PMID- 27667795 TI - Glycosylation and stem cells: Regulatory roles and application of iPSCs in the study of glycosylation-related disorders. AB - Glycosylation refers to the co- and post-translational modification of protein and lipids by monosaccharides or oligosaccharide chains. The surface of mammalian cells is decorated by a heterogeneous and highly complex array of protein and lipid linked glycan structures that vary significantly between different cell types, raising questions about their roles in development and disease pathogenesis. This review will begin by focusing on recent findings that define roles for cell surface protein and lipid glycosylation in pluripotent stem cells and their functional impact during normal development. Then, we will describe how patient derived induced pluripotent stem cells are being used to model human diseases such as congenital disorders of glycosylation. Collectively, these studies indicate that cell surface glycans perform critical roles in human development and disease. PMID- 27667798 TI - Nitrogen, Phosphorus, and Fluorine Tri-doped Graphene as a Multifunctional Catalyst for Self-Powered Electrochemical Water Splitting. AB - Electrocatalysts are required for clean energy technologies (for example, water splitting and metal-air batteries). The development of a multifunctional electrocatalyst composed of nitrogen, phosphorus, and fluorine tri-doped graphene is reported, which was obtained by thermal activation of a mixture of polyaniline coated graphene oxide and ammonium hexafluorophosphate (AHF). It was found that thermal decomposition of AHF provides nitrogen, phosphorus, and fluorine sources for tri-doping with N, P, and F, and simultaneously facilitates template-free formation of porous structures as a result of thermal gas evolution. The resultant N, P, and F tri-doped graphene exhibited excellent electrocatalytic activities for the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). The trifunctional metal-free catalyst was further used as an OER-HER bifunctional catalyst for oxygen and hydrogen gas production in an electrochemical water-splitting unit, which was powered by an integrated Zn-air battery based on an air electrode made from the same electrocatalyst for ORR. The integrated unit, fabricated from the newly developed N, P, and F tri-doped graphene multifunctional metal-free catalyst, can operate in ambient air with a high gas production rate of 0.496 and 0.254 MUL s-1 for hydrogen and oxygen gas, respectively, showing great potential for practical applications. PMID- 27667799 TI - Effects of Candidatus Liberibacter asiaticus on the fitness of the vector Diaphorina citri. AB - AIMS: The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama transmits the bacterium 'Candidatus Liberibacter asiaticus' (Las), which causes citrus huanglongbing (HLB) disease. Although many studies have been conducted on the biology of ACP on different host plants, few have taken the plant, Las bacteria and the vector insect within one context to evaluate the effects of Las on the fitness of ACP under field conditions. Understanding the relationship between Las and ACP is critical for both ACP and HLB disease management. METHODS AND RESULTS: We estimated the development and survival of ACP immatures, the longevity and fecundity of ACP female adults in four treatments (Las-positive or -negative ACP on Las-infected and -free citrus plants). Las-positive ACP immatures developed significantly faster on Las-infected citrus than those on Las-free plants. The fecundity and longevity of Las-positive female adults were also greater, or longer on Las-infected citrus shoots, whereas the survival of Las-positive immatures was significantly lower on Las-infected citrus shoots, compared to those that developed on Las-free plants. Similarly, the intrinsic rate of population increase (rm ) was highest (0.1404) when Las-positive ACP fed on Las infected citrus shoots and the lowest (0.1328) when the Las-negative ACP fed on Las-free citrus shoots. CONCLUSIONS: Both the Las infection in ACP and citrus plants had obvious effects on the biology of ACP. When compared to the Las infection in ACP insects, the Las infection in citrus shoots had a more significant effect on the fitness of ACP. SIGNIFICANCE AND IMPACT OF THE STUDY: To efficiently prevent the occurrence and spread of HLB disease, it is critical to understand the ecological basis of vector outbreaks and disease incidence, especially under field conditions. Thus, this study has increased our understanding of the epidemiology of HLB transmitted by psyllids in nature. PMID- 27667801 TI - A Woman with Leg Numbness and Weakness. PMID- 27667802 TI - A 64-Year-Old Male with Leg Pain. PMID- 27667803 TI - A 60 Year-Old Male with Progressive Back Pain. PMID- 27667800 TI - Clinical and genetic aspects of KBG syndrome. AB - KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat-containing cofactors. We describe 32 KBG patients aged 2-47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent. Macrodontia of permanent upper central incisors was seen in 85%. Other clinical features included short stature, conductive hearing loss, recurrent middle ear infection, palatal abnormalities, and feeding difficulties. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. The subtle facial features of KBG syndrome were recognizable in half the patients. We identified 20 ANKRD11 mutations (18 novel: all truncating) confirmed by Sanger sequencing in 32 patients. Comparison of the two ascertainment groups demonstrated that facial/other typical features were more subtle in the ES group. There were no conclusive phenotype-genotype correlations. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. We propose updated diagnostic criteria/clinical recommendations for KBG syndrome and suggest that inclusion of ANKRD11 will increase the utility of gene panels designed to investigate developmental delay. (c) 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID- 27667804 TI - 11-Year-Old Male with Spinal Mass. PMID- 27667807 TI - Seasonal infection rates of Batrachochytrium dendrobatidis in populations of northern green frog Lithobates clamitans melanota tadpoles. AB - Few studies have documented seasonal variation of Batrachochytrium dendrobatidis (Bd) infection rates in larval amphibians. We identified 4 natural populations of northern green frogs Lithobates clamitans melanota in Pennsylvania (USA) that contained Bd-infected tadpoles during post-wintering collections in May and June, after hibernating tadpoles had overwintered in wetlands. However, we failed to detect infected tadpoles at those wetlands when pre-wintering collections were made in late July through early September. We observed 2 cohorts of tadpoles that appeared to lack Bd-infected individuals in pre-wintering collections, yet contained Bd-infected individuals the following spring. We also observed 4 cohorts of pre-wintering tadpoles that were Bd-free, even though post-wintering tadpoles collected earlier in the year were infected with Bd. Our results suggest that tadpoles either reduce Bd infections during the summer months, and/or infections proliferate sometime prior to (or shortly after) tadpoles emerge from hibernation. It is unlikely that pre-wintering tadpoles were too small to detect Bd zoospores because (1) there was no correlation between Bd zoospore levels and tadpole size or stage, and (2) size was not a significant predictor of infection status. These results suggest that, while sampling larvae can be an effective means of collecting large sample sizes, investigators in our Mid-Atlantic region should conduct sampling by early summer to maximize the chances of detecting Bd. Further research is warranted to determine whether wetland topography and warm, shallow microhabitats within wetlands contribute to a population's ability to drastically reduce Bd prevalence prior to overwintering at ponds. PMID- 27667806 TI - Protozoal-related mortalities in endangered Hawaiian monk seals Neomonachus schauinslandi. AB - Protozoal infections have been widely documented in marine mammals and may cause morbidity and mortality at levels that result in population level effects. The presence and potential impact on the recovery of endangered Hawaiian monk seals Neomonachus schauinslandi by protozoal pathogens was first identified in the carcass of a stranded adult male with disseminated toxoplasmosis and a captive monk seal with hepatitis. We report 7 additional cases and 2 suspect cases of protozoal-related mortality in Hawaiian monk seals between 2001 and 2015, including the first record of vertical transmission in this species. This study establishes case definitions for classification of protozoal infections in Hawaiian monk seals. Histopathology and immunohistochemistry were the primary diagnostic modalities used to define cases, given that these analyses establish a direct link between disease and pathogen presence. Findings were supported by serology and molecular data when available. Toxoplasma gondii was the predominant apicomplexan parasite identified and was associated with 100% of mortalities (n = 8) and 50% of suspect cases (n = 2). Incidental identification of sarcocysts in the skeletal muscle without tissue inflammation occurred in 4 seals, including one co-infected with T. gondii. In 2015, 2 cases of toxoplasmosis were identified ante-mortem and shared similar clinical findings, including hematological abnormalities and histopathology. Protozoal-related mortalities, specifically due to toxoplasmosis, are emerging as a threat to the recovery of this endangered pinniped and other native Hawaiian taxa. By establishing case definitions, this study provides a foundation for measuring the impact of these diseases on Hawaiian monk seals. PMID- 27667808 TI - Amphibian malformations and body condition across an agricultural landscape of northwest Argentina. AB - Agricultural landscapes support large amphibian populations because they provide habitat for many species, although agriculture affects amphibians through various mechanisms. Pollution with agrochemicals is the major threat to amphibian populations after habitat loss, as chemicals alter the ecophysiology of amphibians, putting their health and survival at risk. We aimed to assess the effect of different environments, sites, width of forest buffers and sampling years on the health of amphibians, which was estimated through the prevalence of malformations and body condition. During 3 yr of pitfall trapping, we captured 4491 amphibians. The prevalence of malformations was higher in the croplands than in the forests, while the body condition was better within forests. The prevalence of malformations was higher in the narrower forest site than in the wider forest site. The prevalence of malformations and the body condition were higher in the third year. The prevalence of malformations differed by species. We found 11 types of malformation, which mainly affected limbs and were unilateral or bilaterally asymmetrical. Our results showed that the prevalence of malformations and body condition reflect different aspects of the health of amphibians and that forest individuals are healthier than those from croplands. The results also highlight the importance of spatial configuration besides the conservation of natural habitats to preserve healthy amphibians in agricultural landscapes. The types of malformation that we found suggest that agrochemicals could be an important cause of malformations. PMID- 27667809 TI - Ultrastructure and phylogeny of Ceratomyxa diplodae (Myxosporea: Ceratomyxidae), from gall bladder of European seabass Dicentrarchus labrax. AB - The myxosporean parasite Ceratomyxa diplodae Lubat et al. 1989 sensu Sitja Bobadilla & Alvarez-Pellitero, 1993, originally described from the annular seabream Diplodus annularis in the Adriatic Sea, has subsequently been reported from several other sparid hosts, and also a moronid fish, the European seabass Dicentrarchus labrax from the Mediterranean Sea. Here, molecular identity and additional morphological data are given for this parasite infecting the gall bladder of D. labrax in a southern Portuguese fish farm. In the bile, disporic plasmodia were spherical to subspherical with a smooth surface membrane. Most myxospores were crescent-shaped, 5.1 +/- 0.5 (4.8-6.7) um long (mean +/- SD) and 21.9 +/- 1.0 (20.4-23.9) um thick; a few were more arcuate, 5.7 +/- 0.4 (5.3-6.3) um long and 17.3 +/- 1.0 (16.3-19.1) um thick. The wall consisted of 2 symmetrical valves united along a slightly curved suture line, with moderately tapering to rounded ends. Two spherical polar capsules, measuring 2.9 +/- 0.3 (2.5-3.4) um in diameter, contained a polar filament forming 8 to 9 coils organized in 2 rows. Host species, tissue tropism, and myxospore morphology supported species identification. Phylogenetic analyses of the small subunit ribosomal RNA sequence positioned the parasite among most sparid-infecting Ceratomyxa spp., suggesting the existence of a common ancestor for these species. The acquisition of molecular data from infections of C. diplodae in its original host and in other sparids is essential in order to ascertain if the morphological and biological variations found among reports of this parasite are intra- or inter-specific. PMID- 27667810 TI - Ultrastructural morphogenesis of a virus associated with lymphocystis-like lesions in parore Girella tricuspidata (Kyphosidae: Perciformes). AB - The morphogenesis of large icosahedral viruses associated with lymphocystis-like lesions in the skin of parore Girella tricuspidata is described. The electron lucent perinuclear viromatrix comprised putative DNA with open capsids at the periphery, very large arrays of smooth endoplasmic reticulum (sER), much of it with a reticulated appearance (rsER) or occurring as rows of vesicles. Lysosomes, degenerating mitochondria and virions in various stages of assembly, and paracrystalline arrays were also present. Long electron-dense inclusions (EDIs) with 15 nm repeating units split terminally and curled to form tubular structures internalising the 15 nm repeating structures. These tubular structures appeared to form the virion capsids. Large parallel arrays of sER sometimes alternated with aligned arrays of crinkled cisternae along which passed a uniformly wide (20 nm) thread-like structure. Strings of small vesicles near open capsids may also have been involved in formation of an inner lipid layer. Granules with a fine fibrillar appearance also occurred in the viromatrix, and from the presence of a halo around mature virions it appeared that the fibrils may form a layer around the capsid. The general features of virogenesis of large icosahedral dsDNA viruses, the large amount of ER, particularly rsER and the EDIs, are features of nucleo-cytoplasmic large DNA viruses, rather than features of 1 genus or family. PMID- 27667811 TI - Edwardsiella piscicida-like pathogen in cultured grouper. AB - An Edwardsiella sp. was isolated from the kidney of diseased groupers (Epinephelus aeneus and E. marginatus) cultured in Eilat (Israel, Red Sea). Affected fish presented a severe suppurative nephritis with large abscesses occasionally spreading into the surrounding musculature. Biochemical profiles and phenotypic comparisons failed to provide a clear identification to the species level, and genetic analysis of the 16S subunit failed to discriminate between Edwardsiella piscicida, E. tarda and E. ictaluri. Analysis of the gyrB gene, however, placed the grouper isolates into the E. piscicida-like group, a newly recognized taxon which also encompasses the non-motile strains previously classified as atypical E. tarda. Initial genomic analysis revealed the presence of the Edwardsiella type 3 secretion system (T3SS) but also revealed a pathogenicity island encoding a second T3SS with homology to the locus of enterocyte effacement of Escherichia coli. Further analysis revealed 3 different type 6 secretion systems that were also present in all sequenced isolates of Edwardsiella piscicida-like strains. Based on estimated DNA-DNA hybridization values and the average nucleotide index, the grouper strain fits into the E. piscicida-like phylogroup described as E. anguillarum sp. nov. The peculiarities associated with this isolate and the association of other conspecific piscine isolates from multiple marine and brackish water species suggest a link of the entire E. piscicida-like phylogroup to the marine environment. PMID- 27667812 TI - Francisella noatunensis subsp. noatunensis invades, survives and replicates in Atlantic cod cells. AB - Systemic infection caused by the facultative intracellular bacterium Francisella noatunensis subsp. noatunensis remains a disease threat to Atlantic cod Gadus morhua L. Future prophylactics could benefit from better knowledge on how the bacterium invades, survives and establishes infection in its host cells. Here, facilitated by the use of a gentamicin protection assay, this was studied in primary monocyte/macrophage cultures and an epithelial-like cell line derived from Atlantic cod larvae (ACL cells). The results showed that F. noatunensis subsp. noatunensis is able to invade primary monocyte/macrophages, and that the actin-polymerisation inhibitor cytochalasin D blocked internalisation, demonstrating that the invasion is mediated through phagocytosis. Interferon gamma (IFNgamma) treatment of cod macrophages prior to infection enhanced bacterial invasion, potentially by stimulating macrophage activation in an early step in host defence against F. noatunensis subsp. noatunensis infections. We measured a rapid drop of the initial high levels of internalised bacteria in macrophages, indicating the presence and action of a cellular immune defence mechanism before intracellular bacterial replication took place. Low levels of bacterial internalisation and replication were detected in the epithelial-like ACL cells. The capacity of F. noatunensis subsp. noatunensis to enter, survive and even replicate within an epithelial cell line may play an important role in its ability to infect live fish and transverse epithelial barriers to reach the bacterium's main target cells-the macrophage. PMID- 27667813 TI - Susceptibility of common carp and sunfish to a strain of Francisella noatunensis subsp. orientalis in a challenge experiment. AB - Francisellosis, an emerging disease in many fish species, can cause high mortality in affected populations. Here we investigated the susceptibility of common carp Cyprinus carpio and sunfish Lepomis gibbosus to Francisella noatunensis subsp. orientalis (Fno), and possible transmission of the bacteria between the 2 fish species. In a challenge experiment, 3 groups of each species were injected intraperitoneally (IP) with 3 different doses of an Fno strain no. 9449 of the Norwegian Veterinary Institute, recovered from naturally infected ornamental Malawi cichlids. Infected carp were cohabitated with sunfish and vice versa. Control groups were injected with 0.9M phosphate-buffered saline and cohabitated accordingly. Fish were sampled at different time points. Mortality of challenged sunfish was observed during the first 96 h and reached 56.1%. In the control sunfish, 4 of 16 fish (25%) died within 48 h. In carp, no mortalities or clinical signs were observed during the experiment. General clinical and patho anatomical disease signs of affected sunfish were observed. We detected granulomas in 2 cohabitated sunfish and 1 challenged carp, but could not re isolate Fno from these fish. Fno was successfully cultured from 6 sunfish and 3 carp specimens until 35 d post injection. PCR of spleen and kidney with 16S rDNA Francisella-like bacterium primers 180f and 485r yielded amplicons in 68.3% of challenged sunfish and only 12.2% of challenged carp. We demonstrated that sunfish were susceptible to Fno infection while the carp were not. Horizontal transmission of the agent between the 2 fish species could not be demonstrated. PMID- 27667814 TI - Occurrence of Amblyomma dissimile on wild crocodylians in southern Mexico. AB - Ticks are common ectoparasites of amphibians and reptiles but very few reports of such parasites on crocodylians exist worldwide. Herein, we report the first detailed observations of Amblyomma dissimile Koch, 1844 on the 3 crocodylian species present in Mexico, with the first report of tick parasitism on Crocodylus acutus and the second on Caiman crocodilus chiapasius. This is also the first report of A. dissimile in the state of Quintana Roo. Proportions of infested individuals found in this study ranged from 0.51 to 1.96%, suggesting that tick parasitism in crocodylians is likely opportunistic and occurs when individuals leave the water for terrestrial activities. Tick parasitism does not represent a major threat to crocodylians. The increasing habitat destruction/fragmentation and cattle expansion in southeastern Mexico, however, could increase tick populations and trigger tick parasitism and tick-borne diseases in herpetofauna and other vertebrates, including humans. Thus, studies are needed to better understand these relationships. PMID- 27667815 TI - Paragonimiasis in tuberculosis patients in Nagaland, India. AB - BACKGROUND: One of the infections that mimic tuberculosis (TB) is paragonimiasis (PRG), a foodborne parasitic disease caused by lung flukes of the genus Paragonimus. In the northeastern states of India, TB and PRG are endemic; however, PRG is rarely included in the differential diagnosis of TB. OBJECTIVE: To address limited evidence on the dual burden of TB and PRG in northeastern India, we aimed to document the prevalence of PRG among TB patients using sputum smear, stool examination for children <15 years and ELISA. DESIGN: A cross sectional study of patients receiving TB treatment in the Medecins Sans Frontieres (MSF)-supported TB programme in Mon district, in collaboration with the Regional Medical Research Centre (RMRC), Dibrugarh, Assam, between November 2012 and December 2013. RESULTS: Of 96 patients screened between November 2012 and December 2013, three (3%) had pulmonary PRG and were successfully treated with praziquantel. CONCLUSIONS: PRG should be considered in the TB diagnostic algorithms in PRG-TB dual burden areas. In case of TB-PRG co-infection, it is preferable to treat PRG first followed by anti-TB treatment a few days later. PMID- 27667816 TI - Maxillary anterior en masse retraction using different antero-posterior position of mini screw: a 3D finite element study. AB - BACKGROUND: Nowadays, mini screws are used in orthodontic tooth movement to obtain maximum or absolute anchorage. They have gained popularity among orthodontists for en masse retraction of anterior teeth after first premolar extraction in maximum anchorage cases. The purpose of this study was to determine the type of anterior tooth movement during the time when force was applied from different mini screw placements to the anterior power arm with various heights. METHODS: A finite element method was used for modeling maxillary teeth and bone structure. Brackets, wire, and hooks were also designed for modeling. Two appropriate positions for mini screw in the mesial and distal of the second premolar were designed as fixed nodes. Forces were applied from the mini screw to four different levels of anterior hook height: 0, 3, 6, and 9 mm. Initial tooth movement in eight different conditions was analyzed and calculated with ANSYS software. RESULTS: Rotation of anterior dentition was decreased with a longer anterior power arm and the mesial placement of the mini screw. Bodily movements occurred with the 9-mm height of the power arm in both mini screw positions. Intrusion or extrusion of the anterior teeth segment depended on the level of the mini screw and the edge of the power arm on the Z axis. CONCLUSIONS: According to the findings of this study, the best control in the sagittal plane during anterior en masse retraction was achieved by mesial placement of the mini screw and the 9-mm height of the anterior power arm. Where control in the vertical plane was concerned, distal placement of the mini screw with the 6-mm power arm height had minimum adverse effect on anterior dentition. PMID- 27667819 TI - Identification of Bombyx mori nucleopolyhedrovirus bm58a as an auxiliary gene and its requirement for cell lysis and larval liquefaction. AB - Bombyx mori nucleopolyhedrovirus orf58a (bm58a) and its homologues are highly conserved in genomes of all sequenced group I alphabaculoviruses and its function is still unknown. Transcriptional analysis revealed that bm58a is a very late gene initiated from a late transcriptional start motif TAAG. To examine its role in the virus, a bm58a knockout virus (vBmbm-58a-KO-PH-GFP) was generated through homologous recombination in Escherichia coli. Analysis of fluorescence microscopy, titration assays and electron microscopy examination showed that the deletion of bm58a did not affect viral replication and occlusion bodies formation in vitro, indicating that bm58a is not required for viral propagation. However, vBmbm-58a-KO-PH-GFP did not result in cell lysis when wild-type virus infected cells began to lyse, and the vBmbm-58a-KO-PH-GFP infected cells remained intact until 2 weeks post-infection. Quantification of polyhedra release from cells confirmed this observation. Accordingly, though deletion of bm58a did not reduce Bombyx mori nucleopolyhedrovirus infectivity in vivo in bioassays, it did significantly disrupt the larval liquefaction, reducing the level of polyhedra release from infected host. Immunofluorescence analysis demonstrated that Bm58a was predominantly localized on the cellular membrane at the late stage of infection, which may contribute to its function of facilitating cell lysis and larval liquefaction. Our results suggest that although bm58a is not essential for viral propagation as an auxiliary gene, it is a key factor of virus-induced cell lysis and larval liquefaction in vitro and in vivo. PMID- 27667817 TI - Three-dimensional mapping of cortical bone thickness in subjects with different vertical facial dimensions. AB - BACKGROUND: The purpose of this study was to determine differences in cortical bone thickness among subjects with different vertical facial dimensions using cone beam computed tomography (CBCT). METHODS: From 114 pre-treatment CBCT scans, 48 scans were selected to be included in the study. CBCT-synthesized lateral cephalograms were used to categorize subjects into three groups based on their vertical skeletal pattern. Cortical bone thickness (CBT) at two vertical levels (4 and 7 mm) from the alveolar crest were measured in the entire tooth-bearing region in the maxilla and mandible. RESULTS: Significant group differences were detected with high-angle subjects having significantly narrower inter-radicular CBT at some sites as compared to average- and low-angle subjects. CONCLUSIONS: Inter-radicular cortical bone is thinner in high-angle than in average- or low angle subjects in few selected sites at the vertical height in which mini implants are commonly inserted for orthodontic anchorage. PMID- 27667820 TI - Isotropic thin PTCDA films on GaN(0 0 0 1). AB - The growth of 3, 4, 9, 10-perylene tetracarboxylic dianhydride (PTCDA) on the Ga polar GaN(0 0 0 1) surface has been studied by x-ray photoelectron spectroscopy (XPS), spot profile analysis low-energy electron diffraction (SPA-LEED), near edge x-ray absorption fine structure (NEXAFS), and scanning tunneling microscopy (STM). The stoichiometric ratios derived from XPS indicate that the molecules remain intact upon adsorption on the surface. Furthermore, no chemical shifts can be observed in the C 1s and O 1s core levels with progressing deposition of PTCDA, suggesting none or only weak interactions between the molecules and the substrate. NEXAFS data indicate the PTCDA molecules being oriented with their molecular plane parallel to the surface. High-resolution STM shows PTCDA islands of irregular shape on the sub-micron scale, and together with corresponding SPA LEED data reveals a lateral ordering of the molecules that is compatible with the presence of (1 0 2) oriented PTCDA nano-crystals. SPA-LEED moreover clearly shows the presence of homogeneously distributed rotational domains of two-dimensionally isotropic PTCDA. PMID- 27667821 TI - Spin Hall magnetoresistance in Co2FeSi/Pt thin films: dependence on Pt thickness and temperature. AB - We have investigated the temperature and the Pt layer thickness dependence of the magnetoresistances (MRs) in Co2FeSi/Pt thin films. Based on the field dependent measurements, it can be seen that the spin-current-induced spin Hall magnetoresistance (SMR) plays the dominant role in the MRs in the Co2FeSi/Pt bilayers in the whole temperature range. Meanwhile, a quite small part of anisotropic magnetoresistance (AMR) existed in the MRs. It proved to be originated from magnetic proximity effect (MPE) by measuring the Pt thickness and temperature dependence of the AMR. Moreover, the Co2FeSi layer thickness has much weaker effect on the SMR and AMR compared to the Pt layer thickness. These results indicate that the Co2FeSi/Pt interface is beneficial to be used in the spin-current-induced physical phenomena. PMID- 27667824 TI - Ultrafast heating-induced magnetization switching in ferrimagnets. AB - We study theoretically the light-induced magnetization switching in a binary ferrimagnet of the type [Formula: see text], randomly occupied by two different species of magnetic ions. The localized spins are coupled with spins of itinerant electrons via s-d exchange interaction. Model parameters are chosen so that to achieve similarity between magnetic characteristics of the model and those of ferrimagnetic rare-earth-transition metal GdFeCo alloys. The switching is triggered by heating of the itinerant electrons by a laser pulse. The spin dynamics is governed by the cooling of itinerant electrons, exchange scattering, induced by the s-d exchange interaction and spin-lattice relaxation of the itinerant spins with a characteristic time [Formula: see text]. The dynamics of the localized and itinerant spins is described by coupled rate equations. The main conclusion of this study is that the switching occurs only in a certain temperature range depending on [Formula: see text]. For long [Formula: see text] the switching occurs only below the magnetisation compensation temperature T K. For physically reasonable values of [Formula: see text] this temperature range extends from 0 K to [Formula: see text], where [Formula: see text] is slightly higher than the compensation temperature T K. With further decrease of [Formula: see text] this temperature range shifts to temperatures higher than T K. PMID- 27667823 TI - NDM-producing Enterobacteriaceae in a Chinese hospital, 2014-2015: identification of NDM-producing Citrobacterwerkmanii and acquisition of blaNDM-1-carrying plasmid in vivo in a clinical Escherichia coli isolate. AB - New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae (NPE) shows prevalence in China. Little is known about the mechanisms related to the spread of NPE. Recently, a total of 51 non-duplicated NPE isolates were collected from a tertiary-care hospital in China and analysed for genetic relatedness by PFGE, antimicrobial susceptibility by Etest and sequence type by multilocus sequence typing. S1-PFGE and Southern blot analysis or PCR amplification were used for plasmid profiling. Between 2014 and 2015, 22 Escherichia coli, 10 Klebsiella pneumoniae, 9 Enterobacter cloacae, 2 Enterobacter aerogenes, 3 Providencia rettgeri, 1 Klebsiella oxytoca, 1 Proteus mirabilis, 1 Citrobacter freundii, 1 Citrobacterwerkmanii and 1 Raoultella planticola were identified as NPE. Results of PFGE and multilocus sequence typing showed that most strains were genetically unrelated. Among the 45 blaNDM-carrying plasmids, there were 25 IncX3 plasmids with a size of about 30 to 50 kb, one 100 kb IncX3 plasmid, 11 IncA/C plasmids with a size range from 70 to 300 kb, six 90 to 120 kb IncB/O plasmids, one IncN plasmid with a size of 100 kb and one 140 kb IncFrep plasmid. An NDM-1-producing isolate of C. werkmanii was identified, which had not been reported previously. An Escherichia coli strain was found acquiring a blaNDM-1-carrying IncFrep plasmid in vivo during infection. In conclusion, an NDM-1-producing isolate of C. werkmanii was identified. An Escherichia coli strain acquired a blaNDM-1-carrying plasmid in vivo. IncX3 and IncA/C plasmids with various sizes might have emerged as the main platforms mediating the spread of the blaNDM genes in China. PMID- 27667822 TI - Cross-cultural and socio-demographic correlates of homophobic attitude among university students in three European countries. AB - PURPOSE: The aim of this study was to investigate homophobic attitudes in three European countries: Italy, Albania, and Ukraine. One thousand and forty-eight students were recruited in Italian (n = 766), Albanian (n = 180), and Ukrainian (n = 102) university centers. METHODS: A socio-demographic questionnaire and Homophobia Scale (HS) were administered by our staff. RESULTS: Cross-cultural and significant differences among Italian, Albanian, and Ukrainian students were found on the Homophobia Scale (HS; Italy: mean = 22.26 +/- 16.73; Albania: mean = 38.15 +/- 17.28; Ukraine: mean = 59.18 +/- 16.23). The analysis of socio demographic characteristics revealed that the male gender emerged as main predictor of homophobic attitude in all the three countries, although also a conservative political orientation and the religious belief predict higher homophobia levels in Italy and Albania, particularly. CONCLUSIONS: This study revealed that in these European countries assessed, attitudes toward homosexuality are different. Ukrainians display higher levels of homophobia than Albanians and Italians, confirming the central role of cultural differences in homophobic attitudes. Nevertheless, some socio-demographic aspects such as identification as male have a similar influence on homophobic attitudes in all assessed populations. PMID- 27667826 TI - Predictors of hepatotoxicity among patients treated with antituberculous medication. AB - Introduction: Hepatotoxicity in patients diagnosed with active tuberculosis (TB) is the commonest adverse effect of therapy. We sought to analyse trends in liver function in patients diagnosed with active TB and to determine predictors of hepatotoxicity. Methods: We studied 275 patients with active TB treated at the Mercy University Hospital (Cork, Ireland) from 2009 to 2014 A retrospective review was undertaken of all patients' laboratory data and patient correspondence to determine predictors of hepatotoxicity. Results: A total of 170 (62%) male and 105 (38%) female patients with active TB with a mean age of 44 years were studied. In total 15 patients (6%) required their medication to be stopped or altered as a consequence of hepatotoxicity. There was a significant difference in age between patients with hepatotoxicity (52.95 years) and those that didn't develop hepatotoxicity (41.33 years) ( P <= 0.01). Irish born patients were more likely to develop hepatotoxicity ( P = 0.025). There was no significant association between hepatotoxicity, illicit drug use ( P = 0.211), smoking ( P = 0.95), cavitatory disease ( P = 0.191), site of disease ( p = 0.224), alcohol use ( P = 0.088) or history of alcohol excess ( p = 0.736). Among patients with TB, peak AST values did not occur within the first 2 weeks as widely thought but later (week 10). Conclusion: Our study shows hepatotoxicity as a consequence of antituberculous therapy is common. Hepatotoxicity was more common in older patients and Irish born patients, and resulted in drug interruptions and treatment changes. Given the late peak in AST values at week 10 in patients treated with antituberculous therapy, the authors advocate that liver function tests should be monitored regularly throughout the course of treatment. PMID- 27667827 TI - Radial pressure profiles in a cold-flow gas-solid vortex reactor. AB - A unique normalized radial pressure profile characterizes the bed of a gas-solid vortex reactor over a range of particle densities and sizes, solid capacities, and gas flow rates: 950-1240 kg/m3, 1-2 mm, 2 kg to maximum solids capacity, and 0.4-0.8 Nm3/s (corresponding to gas injection velocities of 55-110 m/s), respectively. The combined momentum conservation equations of both gas and solid phases predict this pressure profile when accounting for the corresponding measured particle velocities. The pressure profiles for a given type of particles and a given solids loading but for different gas injection velocities merge into a single curve when normalizing the pressures with the pressure value downstream of the bed. The normalized-with respect to the overall pressure drop-pressure profiles for different gas injection velocities in particle-free flow merge in a unique profile. PMID- 27667828 TI - MEET THE PRESIDENT. PMID- 27667829 TI - The Tweet Heard Round the (Health Professions) World. PMID- 27667830 TI - Are Great Teachers Great Storytellers? PMID- 27667831 TI - Debating the Effectiveness and Necessity of Tenure in Pharmacy Education. AB - Academic tenure is a controversial and highly debated topic. Is tenure truly outdated or does it simply need to be reformed? On one hand, the tenure system has shortcomings including deincentivizing productive faculty members, inconsistent application of tenure policies and procedures, and the potential for discrimination during tenure decisions. On the other hand, the tenure system is a long held tradition in the academy, essential in higher education to ensure academic standards and values are upheld in the best interest of students. It provides faculty members with the academic freedom to try innovative teaching strategies and conduct research and assists with faculty retention and recruitment. Regardless of one's opinion, the tenure debate is not going away and warrants further discussion. This paper represents the work of a group of academic leaders participating in the 2014-2015 AACP Academic Leadership Fellowship Program. This work was presented as a debate at the 2015 AACP Interim Meeting in Austin, TX in February 2015. PMID- 27667832 TI - Using Social Cognitive Theory to Explain the Intention of Final-year Pharmacy Students to Undertake a Higher Degree in Pharmacy Practice Research. AB - Objective. To develop and test a conceptual model that hypothesized student intention to undertake a higher degree in pharmacy practice research (PPR) would be increased by self-efficacy, outcome expectancy, and the social influence of faculty members. Methods. Cross-sectional surveys were completed by 387 final year pharmacy undergraduates enrolled in 2012 and 2013. Structural equation modeling was used to explore relationships between variables and intention. Results. Fit indices were good. The model explained 55% of the variation in intention. As hypothesized, faculty social influence increased self-efficacy and indirectly increased outcome expectancy and intention. Conclusion. To increase pharmacy students' orientation towards a career in PPR, faculty members could use their social influence by highlighting PPR in their teaching. PMID- 27667833 TI - Survey of Pharmacy Schools' Approaches and Attitudes toward Curricular Integration. AB - Objective. To identify ways in which curricular integration is addressed in US pharmacy schools, the structure of therapeutics and foundational science courses, and perceptions of the effects current curricular integration methods have on student learning. Methods. An electronic survey was sent to academic leaders representing 131 pharmacy schools in the United States. Frequency data was tabulated and demographic analysis was performed. Results. Respondent data represents 94 schools of pharmacy. Arranging similar content from various disciplines in a course, a skills laboratory and pharmacy practice experiences were the most common methods for achieving curricular integration. More than one half of the schools indicated that foundational sciences were integrated with therapeutics. The most common reported challenge to curricular integration was logistics. Conclusion. Pharmacy education in the United States has evolved in addressing curricular integration in the curricula, which is consistent with changes in accreditation standards. Most pharmacy schools reported a variety of methods for achieving the intent of curricular integration. PMID- 27667834 TI - Assessing the Value of Online Learning and Social Media in Pharmacy Education. AB - Objective. To assess student preferences regarding online learning and technology and to evaluate student pharmacists' social media use for educational purposes. Methods. An anonymous 36-question online survey was administered to third-year student pharmacists enrolled in the Drug Information and Clinical Literature Evaluation course. Results. Four hundred thirty-one students completed the survey, yielding a 96% response rate. The majority of students used technology for academic activities, with 90% using smart phones and 91% using laptop computers. Fifty-eight percent of students also used social networking websites to communicate with classmates. Conclusion. Pharmacy students frequently use social media and some online learning methods, which could be a valuable avenue for delivering or supplementing pharmacy curricula. The potential role of social media and online learning in pharmacy education needs to be further explored. PMID- 27667835 TI - An Examination of Correlations between MMI scores and Pharmacy School GPA. AB - Objective. To investigate the correlation of mean admission multiple mini interview (MMI) scores with cumulative and overall GPA across didactic years 1-3 in the doctor of pharmacy (PharmD) curriculum. Methods. The mean admission MMI score and cumulative and overall GPA for first year (P1), second year (P2), and third year (P3) students in the PharmD curriculum was used to conduct a multiple regression analysis and to calculate a Pearson correlation coefficient. Statistical analysis was performed using SPSS, v20. Results. A negative correlation between mean admission MMI and overall GPA was observed for P1 students and P2 students. A significant positive correlation was observed between mean admission MMI and overall GPA for P3 students. Conclusion. A weak association between mean admission MMI score and GPA was observed, and the direction of the association between MMI and GPA was mixed across cohorts of students in the PharmD curriculum. Further research is needed that includes measurement of noncognitive outcomes and continued validation of the MMI for use in pharmacy school admissions. PMID- 27667836 TI - The Effect of Prerequisite Pharmacodynamics Course Timing on Student Performance in Pharmacotherapy Courses. AB - Objective. To evaluate the impact that decreasing the time from 12 to three months between prerequisite pharmacodynamics courses and their corresponding pharmacotherapy courses had on overall student performance in the pharmacotherapy courses measured by course examination scores. Methods. Two cohorts of second professional year (P2) and third professional year (P3) classes, respectively, following different curriculum plans, simultaneously took two pharmacotherapy courses (infectious disease and neoplastic disease). Admission data (age, gender, prior bachelor's degree status, grade point average (GPA), Pharmacy College Admission Test (PCAT) score, and interview score) were collected to establish baseline characteristics between the two cohorts. Examination scores in the corresponding prerequisite pharmacodynamics and pharmacotherapy courses were also collected. The variable was the difference in time each cohort experienced between the prerequisite pharmacodynamics courses and the subsequent pharmacotherapy courses. Results. No difference was found in baseline admission characteristics between the two cohorts, except for increased average age, which favored the P2 cohort. In the infectious disease pharmacotherapy course, the P3 cohort performed better than the P2 cohort as measured by average examination scores. In the neoplastic disease pharmacotherapy course, the P3 cohort also achieved significant higher average examination scores than the P2 cohort. The P3 cohort achieved higher overall scores than the P2 cohort in both courses despite a longer interval between the applicable pharmacodynamic and pharmacotherapy courses (12 months vs 3 months, respectively). Conclusion. Shortening the time interval from 12 months to three months between prerequisite and requisite courses did not result in improved, or even equivalent, academic performance relative to the P2 cohort that had only a 3-month interval between courses. Placing like content closer together, as the only intervention, is not enough to ensure improved student performance measured by examination scores in corresponding requisite courses. PMID- 27667837 TI - A Systematic Review of Extramural Presentations and Publications from Pharmacy Student Research Programs. AB - Objective. To conduct a systematic review of reports of pharmacy student research programs that describes the programs and resulting publications or presentations. Methods. To be eligible for the review, reports had to be in English and indicate that students were required to collect, analyze data, and report or present findings. The outcome variables were extramural posters/presentations and publications. Results. Database searches resulted in identification of 13 reports for 12 programs. Two-thirds were reports of projects required for a course or for graduation, and the remaining third were elective (participation was optional). Extramural posters resulted from 75% of the programs and publications from 67%. Conclusion. Although reporting on the outcomes of student research programs is limited, three-quarters of the programs indicated that extramural presentations, publications, or both resulted from student research. Additional research is needed to identify relevant outcomes of student research programs in pharmacy. PMID- 27667838 TI - A Retrospective Study on Students' and Teachers' Perceptions of the Reflective Ability Clinical Assessment. AB - Objective. To evaluate student and teacher perceptions of the utility of the Reflective Ability Clinical Assessment (RACA) in an undergraduate pharmacy curriculum at an Australian university. Methods. A mixed-method study comprising the administration of a 7-item student survey on a 6-point Likert-type scale and a 45-minute focus group/phone interview with teachers. Results. Student (n=199) and teaching staff respondents (n=3) provided their perceptions of the implementation of the new educational tool. Student responses showed significant positive correlations between self-directed learning, counseling skills, relevance to future practice, and performance in an oral examination. Seven key themes emerged from the teacher interviews. Conclusion. The study revealed both students and teachers perceive the RACA as an effective educational tool that may enhance skill development for future clinical practice. PMID- 27667839 TI - Time Spent, Workload, and Student and Faculty Perceptions in a Blended Learning Environment. AB - Objective. To evaluate student perception and time spent on asynchronous online lectures in a blended learning environment (BLE) and to assess faculty workload and perception. Methods. Students (n=427) time spent viewing online lectures was measured in three courses. Students and faculty members completed a survey to assess perceptions of a BLE. Faculty members recorded time spent creating BLEs. Results. Total time spent in the BLE was less than the allocated time for two of the three courses by 3-15%. Students preferred online lectures for their flexibility, students' ability to apply information learned, and congruence with their learning styles. Faculty members reported the BLE facilitated higher levels of learning during class sessions but noted an increase in workload. Conclusion. A BLE increased faculty workload but was well received by students. Time spent viewing online lectures was less than what was allocated in two of the three courses. PMID- 27667841 TI - Using Text Analytics of AJPE Article Titles to Reveal Trends In Pharmacy Education Over the Past Two Decades. AB - Objective. To identify trends in pharmacy education during last two decades using text mining. Methods. Articles published in the American Journal of Pharmaceutical Education (AJPE) in the past two decades were compiled in a database. Custom text analytics software was written using Visual Basic programming language in the Visual Basic for Applications (VBA) editor of Excel 2007. Frequency of words appearing in article titles was calculated using the custom VBA software. Data were analyzed to identify the emerging trends in pharmacy education. Results. Three educational trends emerged: active learning, interprofessional, and cultural competency. Conclusion. The text analytics program successfully identified trends in article topics and may be a useful compass to predict the future course of pharmacy education. PMID- 27667840 TI - Students' Opinions on Summative Team Assessments in a Three-Year Concentrated Pharmacy Curriculum. AB - Objective. To investigate student opinions of team assessment. Methods. University of Maryland Eastern Shore School of Pharmacy first-year (P1) to third year (P3) students (n=125) completed an online survey regarding team assessments. Students rated their opinions on a Likert scale. Responses were examined using Mann-Whitney U test with respect to academic performance and class. Results. One hundred twenty-five students (75%) completed the survey. A majority of students agreed that team assessment was beneficial (90%). In contrast, 78% of the students perceived that the discussion helped clarify misconceptions. Students were not in agreement on occurrence of free riders (51%) and the use of peer evaluation (38%). Overall, students ranked the benefits of team assessment as improving individual score, then promoting collaboration, followed by enhancing understanding of material. Conclusion. Students had favorable opinions regarding team assessment. Educational benefits of team assessments include enhanced understanding of the material, being a meaningful activity for promoting collaboration, and developing communication skills. PMID- 27667842 TI - Using the Pharmacist Interaction Tracking Tool for Capturing Student-Patient Interactions in Direct and Simulated Patient Care Activities. AB - Objective. To create and implement a standardized data collection tool for capturing student-patient interactions in direct and simulated patient care activities. Design. Faculty members and students determined key elements, design, and an implementation plan for the tool, which was to be used by students across professional years to quantify numbers and types of interactions with patients for tracking student progression toward achievement of curricular outcomes. Assessment. During the 2013-2014 academic year, 27 778 entries were completed, with 17 767 (64%) advanced pharmacy practice experiences, 7272 (26%) introductory pharmacy practice experiences, and 2739 (10%) simulation. Direct patient care interactions occurred with 11 090 patients and 10 983 providers, with 14 252 drug related problems identified. Data was used by students for their professional portfolios, by administrators for curricular assessment, and to student impact on patient care. Conclusion. The PITT Form enabled the collection of data from actual and simulated patient care activities, allowed for curricular assessment of activities across years, and was used by individual students. PMID- 27667843 TI - An Elective Course to Train Student Pharmacists to Deliver a Community-based Group Diabetes Prevention Program. AB - Objective. To develop and assess the impact of an elective course aimed at improving student knowledge of and confidence in delivering a group diabetes prevention program. Design. Two colleges of pharmacy collaborated to develop a 2 credit elective course using didactic and active-learning strategies to prepare students to serve as lifestyle coaches offering a proven group diabetes prevention program. Assessment. Students' confidence in their ability to deliver a group diabetes prevention program increased as a result of the class. However, their knowledge of diabetes prevention facts was unchanged from baseline. Conclusion. A diabetes prevention elective course improved students' confidence in their ability to teach a diabetes prevention program. PMID- 27667844 TI - Incorporating Health Information Technology and Pharmacy Informatics in a Pharmacy Professional Didactic Curriculum -with a Team-based Learning Approach. AB - Objective. To incorporate a pharmacy informatics program in the didactic curriculum of a team-based learning institution and to assess students' knowledge of and confidence with health informatics during the course. Design. A previously developed online pharmacy informatics course was adapted and implemented into a team-based learning (TBL) 3-credit-hour drug information course for doctor of pharmacy (PharmD) students in their second didactic year. During a period of five weeks (15 contact hours), students used the online pharmacy informatics modules as part of their readiness assurance process. Additional material was developed to comply with the TBL principles. Online pre/postsurveys were administered to evaluate knowledge gained and students' perceptions of the informatics program. Assessment. Eighty-three second-year students (84% response rate) completed the surveys. Participants' knowledge of electronic health records, computerized physician order entry, pharmacy information systems, and clinical decision support was significantly improved. Additionally, their confidence significantly improved in terms of describing health informatics terminology, describing the benefits and barriers of using health information technology, and understanding reasons for systematically processing health information. Conclusion. Students responded favorably to the incorporation of pharmacy informatics content into a drug information course using a TBL approach. Students met the learning objectives of seven thematic areas and had positive attitudes toward the course after its completion. PMID- 27667845 TI - The Racial and Ethnic Representation of Faculty in US Pharmacy Schools and Colleges. AB - Objective. To describe the representation of racial and ethnic minorities among faculty members (faculty) in schools and colleges of pharmacy (COP) compared to US Census Bureau data; to evaluate the representation of racial and ethnic minorities in historically black colleges and universities (HBCUs), newer doctor of pharmacy (PharmD) programs, and PharmD programs with a religious affiliation compared with all pharmacy programs; and to compare racial and ethnic pharmacy faculty data to trends in medical and dental schools, and all higher education. Methods. Information was obtained from national databases and published reports; data was comparatively evaluated. Results. Compared to the general population, Asians are overrepresented in pharmacy, while all other minority groups are underrepresented. The HBCUs, newer schools, and religious-affiliated institutions have greater numbers of African American/Black faculty. Newer schools also have better representation of Hispanic faculty. Pharmacy has been more successful than medicine and dentistry in recruiting African American/Black faculty, but lag behind dental schools in their representation of Hispanic faculty. Conclusion. To meet the health care needs of the population, we recommend the implementation of short-term and long-term diversity and inclusion strategies that address minority representation in COP. PMID- 27667846 TI - Response to Brock et al: "Health Care Education Must Be More of a Team Sport". PMID- 27667848 TI - Correction to "A Comparative Analysis of Perceptions of Pharmacy Students' Stress and Stressors across Two Multicampus Universities". AB - [This corrects the article DOI: 10.5688/ajpe80582.]. PMID- 27667847 TI - Response to Paradis: "Health Care Education Must Be More of a Team Sport". PMID- 27667849 TI - The Pharmacy Student Population: Applications Received 2014-15, Degrees Conferred 2014-15, Fall 2015 Enrollments. PMID- 27667850 TI - A novel statistical method for behaviour sequence analysis and its application to birdsong. AB - Complex vocal signals, such as birdsong, contain acoustic elements that differ in both order and duration. These elements may convey socially relevant meaning, both independently and through their interactions, yet statistical methods that combine order and duration data to extract meaning have not, to our knowledge, been fully developed. Here we design novel semi-Markov methods, Bayesian estimation and classification trees to extract order and duration information from behavioural sequences and apply these methods to songs produced by male European starlings, Sturnus vulgaris, in two social contexts in which the function of song differs: a spring (breeding) and autumn (nonbreeding) context. Additionally, previous data indicate that damage to the medial preoptic nucleus (POM), a brain area known to regulate male sexually motivated behaviour, affects structural aspects of starling song such that males in a sexually relevant context (i.e. spring) sing shorter songs than appropriate for this context. We further test the utility of our statistical approach by comparing attributes of song structure in POM-lesioned males to song produced by control spring and autumn males. Spring and autumn songs were statistically separable based on the duration and order of phrase types. Males produced more structurally complex aspects of song in spring than in autumn. Spring song was also longer and more stereotyped than autumn song, both attributes used by females to select mates. Songs produced by POM-lesioned males in some cases fell between measures of spring and autumn songs but differed most from songs produced by autumn males. Overall, these statistical methods can effectively extract biologically meaningful information contained in many behavioural sequences given sufficient sample sizes and replication numbers. PMID- 27667851 TI - Low Birth Weight, Preschool Education, and School Remediation. AB - Studies have documented a strong relationship between low birth weight status and adverse child outcomes such as poor school performance and need for special education services. Following a cohort of over 1,300 low-income and predominately African American children in the Chicago Longitudinal Study we investigated whether birth weight and family socio-economic risk measured at the time of the child's birth predicts placement into special education classes or grade retention in elementary school. Contrary to previous research, we found that low birth weight (< 5 1/2 pounds) does not predict special education placement. Rather, these children (especially boys) were more likely to be retained in grade as an alternative approach to addressing poor school performance. Family socio economic risk at birth was a significant predictor of the need for remedial services. We also assessed whether a high-quality preschool program offered at ages 3 and 4 can reduce the negative effects of low family SES and birth weight on the need for special education and grade retention. Preschool participation in the Child-Parent Centers was found to reduce the likelihood of school remediation. The effects of preschool were greater for children from families with higher levels of socio-economic disadvantage. The beneficial effects of preschool on special education placement were also larger for boys than girls. PMID- 27667853 TI - Coho salmon spawner mortality in western US urban watersheds: bioinfiltration prevents lethal storm water impacts. AB - Adult coho salmon Oncorhynchus kisutch return each autumn to freshwater spawning habitats throughout western North America. The migration coincides with increasing seasonal rainfall, which in turn increases storm water run-off, particularly in urban watersheds with extensive impervious land cover. Previous field assessments in urban stream networks have shown that adult coho are dying prematurely at high rates (>50%). Despite significant management concerns for the long-term conservation of threatened wild coho populations, a causal role for toxic run-off in the mortality syndrome has not been demonstrated.We exposed otherwise healthy coho spawners to: (i) artificial storm water containing mixtures of metals and petroleum hydrocarbons, at or above concentrations previously measured in urban run-off; (ii) undiluted storm water collected from a high traffic volume urban arterial road (i.e. highway run-off); and (iii) highway run-off that was first pre-treated via bioinfiltration through experimental soil columns to remove pollutants.We find that mixtures of metals and petroleum hydrocarbons - conventional toxic constituents in urban storm water - are not sufficient to cause the spawner mortality syndrome. By contrast, untreated highway run-off collected during nine distinct storm events was universally lethal to adult coho relative to unexposed controls. Lastly, the mortality syndrome was prevented when highway run-off was pretreated by soil infiltration, a conventional green storm water infrastructure technology.Our results are the first direct evidence that: (i) toxic run-off is killing adult coho in urban watersheds, and (ii) inexpensive mitigation measures can improve water quality and promote salmon survival. Synthesis and applications. Coho salmon, an iconic species with exceptional economic and cultural significance, are an ecological sentinel for the harmful effects of untreated urban run-off. Wild coho populations cannot withstand the high rates of mortality that are now regularly occurring in urban spawning habitats. Green storm water infrastructure or similar pollution prevention methods should be incorporated to the maximal extent practicable, at the watershed scale, for all future development and redevelopment projects, particularly those involving transportation infrastructure. PMID- 27667852 TI - Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015) AB - Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation. PMID- 27667854 TI - Binuclear copper(II) complexes discriminating epimeric glycosides and alpha- and beta-glycosidic bonds in aqueous solution. AB - Two chiral binuclear copper(II) complexes were synthesized and characterized for the first time as efficient chemoselective catalysts for the hydrolysis of aryl glycosides and disaccharides in aqueous solution at near neutral pH. Under these conditions, discrimination of epimeric aryl alpha-glycopyranosides was observed both by 29-fold different reaction rates and 3-fold different proficiency of the catalyst. Additionally, large differentiation of the nature of alpha- and beta- glycosidic bond in aryl glycosides as model compounds is apparent, but also noted in selected disaccharides. The influence of the chirality of the complexes and the role of the configuration of the carbohydrate upon interaction with the catalyst is discussed in detail. Lastly, a putative mechanism for the metal complex-catalyzed hydrolysis is derived from the experimental evidence pointing at deprotonation of the hydroxyl group at C-2 as a pre-requisite for glycoside hydrolysis. PMID- 27667855 TI - Synthesis and chemical reactivity of a 6-Me-3,2-hydroxypyridinone dithiazolide with primary amines: a route to new hexadentate chelators for hard metal(III) ions. AB - A hydroxypyridinone building block, bifunctionalized with thiazoline, has been prepared from orthogonally protected 2-(3-(benzyloxy)-4-(ethoxycarbonyl)-6-methyl 2-oxopyridin-1(2H)-yl) acetic acid. The reactivity of the dithiazolide has been explored with two primary amines, leading to the synthesis and characterization of four new hexadentate ligands. Their complexes with selected hard trivalent ions pertinent to potential molecular imaging applications have been surveyed. PMID- 27667856 TI - Coinfection Dynamics of Two Diseases in a Single Host Population. AB - A susceptible-infectious-susceptible (SIS) epidemic model that describes the coinfection and cotransmission of two infectious diseases spreading through a single population is studied. The host population consists of two subclasses: susceptible and infectious, and the infectious individuals are further divided into three subgroups: those infected by the first agent/pathogen, the second agent/pathogen, and both. The basic reproduction numbers for all cases are derived which completely determine the global stability of the system if the presence of one agent/pathogen does not affect the transmission of the other. When the constraint on the transmissibility of the dually infected hosts is removed, we introduce the invasion reproduction number, compare it with two other types of reproduction number and show the uniform persistence of both diseases under certain conditions. Numerical simulations suggest that the system can display much richer dynamics such as backward bifurcation, bistability and Hopf bifurcation. PMID- 27667859 TI - Conscious Action/Zombie Action. AB - I argue that the neural realizers of experiences of trying (that is, experiences of directing effort towards the satisfaction of an intention) are not distinct from the neural realizers of actual trying (that is, actual effort directed towards the satisfaction of an intention). I then ask how experiences of trying might relate to the perceptual experiences one has while acting. First, I assess recent zombie action arguments regarding conscious visual experience, and I argue that contrary to what some have claimed, conscious visual experience plays a causal role for action control in some circumstances. Second, I propose a multimodal account of the experience of acting. According to this account, the experience of acting is (at the very least) a temporally extended, co-conscious collection of agentive and perceptual experiences, functionally integrated and structured both by multimodal perceptual processing as well as by what an agent is, at the time, trying to do. PMID- 27667858 TI - Rapid growth and concerted sexual transitions by a bloom of the harmful dinoflagellate Alexandrium fundyense (Dinophyceae). AB - Transitions between life cycle stages by the harmful dinoflagellate Alexandrium fundyense are critical for the initiation and termination of its blooms. To quantify these transitions in a single population, an Imaging FlowCytobot (IFCB), was deployed in Salt Pond (Eastham, Massachusetts), a small, tidally flushed kettle pond that hosts near annual, localized A. fundyense blooms. Machine-based image classifiers differentiating A. fundyense life cycle stages were developed and results were compared to manually corrected IFCB samples, manual microscopy based estimates of A. fundyense abundance, previously published data describing prevalence of the parasite Amoebophrya, and a continuous culture of A. fundyense infected with Amoebophrya. In Salt Pond, a development phase of sustained vegetative division lasted approximately 3 weeks and was followed by a rapid and near complete conversion to small, gamete cells. The gametic period (~3 d) coincided with a spike in the frequency of fusing gametes (up to 5% of A. fundyense images) and was followed by a zygotic phase (~4 d) during which cell sizes returned to their normal range but cell division and diel vertical migration ceased. Cell division during bloom development was strongly phased, enabling estimation of daily rates of division, which were more than twice those predicted from batch cultures grown at similar temperatures in replete medium. Data from the Salt Pond deployment provide the first continuous record of an A. fundyense population through its complete bloom cycle and demonstrate growth and sexual induction rates much higher than are typically observed in culture. PMID- 27667857 TI - Food Perceptions and Dietary Behavior of American-Indian Children, Their Caregivers, and Educators: Formative Assessment Findings from Pathways. AB - Dietary findings from a school-based obesity prevention project (Pathways) are reported for children from six different American-Indian nations. A formative assessment was undertaken with teachers, caregivers, and children from nine schools to design a culturally appropriate intervention, including classroom curriculum, food service, physical education, and family components. This assessment employed a combination of qualitative and quantitative methods (including direct observations, paired-child in-depth interviews, focus groups with child caregivers and teachers, and semistructured interviews with caregivers and foodservice personnel) to query local perceptions and beliefs about foods commonly eaten and risk behaviors associated with childhood obesity at home, at school, and in the community. An abundance of high-fat, high-sugar foods was detected in children's diets described by caregivers, school food-service workers, and the children themselves. Although children and caregivers identified fruits and vegetables as healthy food choices, this knowledge does not appear to influence actual food choices. Frequent high-fat/high-sugar food sales in the schools, high-fat entrees in school meals, the use of food rewards in the classroom, rules about finishing all of one's food, and limited family resources are some of the competing factors that need to be addressed in the Pathways intervention. PMID- 27667860 TI - Application of Independent Component Analysis Techniques in Speckle Noise Reduction of Retinal OCT Images. AB - Optical Coherence Tomography (OCT) is an emerging technique in the field of biomedical imaging, with applications in ophthalmology, dermatology, coronary imaging etc. OCT images usually suffer from a granular pattern, called speckle noise, which restricts the process of interpretation. Therefore the need for speckle noise reduction techniques is of high importance. To the best of our knowledge, use of Independent Component Analysis (ICA) techniques has never been explored for speckle reduction of OCT images. Here, a comparative study of several ICA techniques (InfoMax, JADE, FastICA and SOBI) is provided for noise reduction of retinal OCT images. Having multiple B-scans of the same location, the eye movements are compensated using a rigid registration technique. Then, different ICA techniques are applied to the aggregated set of B-scans for extracting the noise-free image. Signal-to-Noise-Ratio (SNR), Contrast-to-Noise Ratio (CNR) and Equivalent-Number-of-Looks (ENL), as well as analysis on the computational complexity of the methods, are considered as metrics for comparison. The results show that use of ICA can be beneficial, especially in case of having fewer number of B-scans. PMID- 27667862 TI - Do Inquiring Minds Have Positive Attitudes? The Science Education of Preservice Elementary Teachers. AB - Due to their potential impact on students' cognitive and non-cognitive outcomes, the negative attitudes towards science held by many elementary teachers are a critical issue that needs to be addressed. This study focuses on the science education of pre-service elementary teachers with the goal of improving their attitudes before they begin their professional lives as classroom teachers. Specifically, this study builds on a small body of research to examine whether exposure to inquiry-based science content courses that actively involve students in the collaborative process of learning and discovery can promote a positive change in attitudes towards science across several different dimensions. To examine this issue, surveys and administrative data were collected from over 200 students enrolled in the Hands on Science (HoS) program for pre-service teachers at the University of Texas at Austin, as well as more than 200 students in a comparison group enrolled in traditional lecture-style classes. Quantitative analyses reveal that after participating in HoS courses, pre-service teachers significantly increased their scores on scales measuring confidence, enjoyment, anxiety, and perceptions of relevance, while those in the comparison group experienced a decline in favorable attitudes to science. These patterns offer empirical support for the attitudinal benefits of inquiry-based instruction and have implications for the future learning opportunities available to students at all education levels. PMID- 27667861 TI - Stochastic Kinetics of Nascent RNA. AB - The stochastic kinetics of transcription is typically inferred from the distribution of RNA numbers in individual cells. However, cellular RNA reflects additional processes downstream of transcription, hampering this analysis. In contrast, nascent (actively transcribed) RNA closely reflects the kinetics of transcription. We present a theoretical model for the stochastic kinetics of nascent RNA, which we solve to obtain the probability distribution of nascent RNA per gene. The model allows us to evaluate the kinetic parameters of transcription from single-cell measurements of nascent RNA. The model also predicts surprising discontinuities in the distribution of nascent RNA, a feature which we verify experimentally. PMID- 27667863 TI - Understanding handpump sustainability: Determinants of rural water source functionality in the Greater Afram Plains region of Ghana. AB - Safe drinking water is critical to human health and development. In rural sub Saharan Africa, most improved water sources are boreholes with handpumps; studies suggest that up to one third of these handpumps are nonfunctional at any given time. This work presents findings from a secondary analysis of cross-sectional data from 1509 water sources in 570 communities in the rural Greater Afram Plains (GAP) region of Ghana; one of the largest studies of its kind. 79.4% of enumerated water sources were functional when visited; in multivariable regressions, functionality depended on source age, management, tariff collection, the number of other sources in the community, and the district. A Bayesian network (BN) model developed using the same data set found strong dependencies of functionality on implementer, pump type, management, and the availability of tools, with synergistic effects from management determinants on functionality, increasing the likelihood of a source being functional from a baseline of 72% to more than 97% with optimal management and available tools. We suggest that functionality may be a dynamic equilibrium between regular breakdowns and repairs, with management a key determinant of repair rate. Management variables may interact synergistically in ways better captured by BN analysis than by logistic regressions. These qualitative findings may prove generalizable beyond the study area, and may offer new approaches to understanding and increasing handpump functionality and safe water access. PMID- 27667864 TI - Dextroamphetamine and Pramipexole Combination for Treatment-Resistant Unipolar Depression. PMID- 27667865 TI - Evidence for Using Doxazosin in the Treatment of Posttraumatic Stress Disorder. AB - There is evidence that doxazosin is effective in the treatment of posttraumatic stress disorder (PTSD). Doxazosin is a "me-too" drug of prazosin. Doxazosin has an improved absorption profile and this likely minimizes the risk for unintended adverse hypotensive effects. The availability of doxazosin in the gastrointestinal therapeutic system (GITS) form permits a higher initial daily dose (4 mg/day) while avoiding significant first-dose side effects. The treatment of PTSD with prazosin has several disadvantages due to its short duration of action (6-8 hours), which results in multiple doses being required. Prazosin may wear off and this may lead to nightmares in the latter half of the sleep. Doxazosin has significant advantages over prazosin in clinical practice because it has a long half-life and requires only once-daily dosing. This may lead to better adherence and greater effectiveness in the treatment of PTSD. PMID- 27667866 TI - Nickel-Catalyzed Synthesis of Ketones from Alkyl Halides and Acid Chlorides: Preparation of Ethyl 4-Oxododecanoate. PMID- 27667867 TI - Development of a Three-Factor Psychological Sense of Community Scale. AB - A variety of measures of sense of community have been developed, but the identification of latent factors in developed scales to measure this construct have encountered significant psychometric problems involving reliability and validity. We present a new measure called the Psychological Sense of Community Scale, which is based on 3 distinct ecological domains involving the individual, microsystem and macrosystem. We used an exploratory factor analysis to investigate our three theoretical domains involving Self (identity and importance to self), Membership (social relationships), and Entity (a group's organization and purpose). Three theoretically derived factors emerged with good measurement model fit, internal reliabilities, and convergent validity. Our study also found multiplicative over additive effects, suggesting each of the 3 domains is necessary to understand the experience of sense of community. This scale can be adapted to a variety of contexts and situations in future research. PMID- 27667868 TI - Child Maltreatment and Offending Behavior: Gender-Specific Effects and Pathways. AB - Although expected, distinct gender-specific trajectories from early victimization to later offending have not been well explored. Consequently, this study assessed the association between child maltreatment (ages 0-11) and offending behavior within gender-specific models. Prospectively collected data, including official measures of maltreatment and offending, derived from the Chicago Longitudinal Study, a panel study of 1,539 low-income minority participants, Multivariate probit analyses revealed that maltreatment significantly predicted delinquency for males but not females yet forged a significant relation to adult crime for both genders. Exploratory confirmatory and comparative analyses suggested that mechanisms linking maltreatment to adult crime primarily differed across gender. For males, childhood-era externalizing behavior and school commitment along with adolescent-era socioemotional skills, delinquency, and educational attainment fully explained the maltreatment-crime nexus. For females, childhood-era parent factors along with adolescent indicators of externalizing behavior, cognitive performance, mobility and educational attainment partially mediated the maltreatment-crime relation. Implications of results were explored. PMID- 27667869 TI - Subglacial discharge at tidewater glaciers revealed by seismic tremor. AB - Subglacial discharge influences glacier basal motion and erodes and redeposits sediment. At tidewater glacier termini, discharge drives submarine terminus melting, affects fjord circulation, and is a central component of proglacial marine ecosystems. However, our present inability to track subglacial discharge and its variability significantly hinders our understanding of these processes. Here we report observations of hourly to seasonal variations in 1.5-10 Hz seismic tremor that strongly correlate with subglacial discharge but not with basal motion, weather, or discrete icequakes. Our data demonstrate that vigorous discharge occurs from tidewater glaciers during summer, in spite of fast basal motion that could limit the formation of subglacial conduits, and then abates during winter. Furthermore, tremor observations and a melt model demonstrate that drainage efficiency of tidewater glaciers evolves seasonally. Glaciohydraulic tremor provides a means by which to quantify subglacial discharge variations and offers a promising window into otherwise obscured glacierized environments. PMID- 27667870 TI - Rising methane emissions from northern wetlands associated with sea ice decline. AB - The Arctic is rapidly transitioning toward a seasonal sea ice-free state, perhaps one of the most apparent examples of climate change in the world. This dramatic change has numerous consequences, including a large increase in air temperatures, which in turn may affect terrestrial methane emissions. Nonetheless, terrestrial and marine environments are seldom jointly analyzed. By comparing satellite observations of Arctic sea ice concentrations to methane emissions simulated by three process-based biogeochemical models, this study shows that rising wetland methane emissions are associated with sea ice retreat. Our analyses indicate that simulated high-latitude emissions for 2005-2010 were, on average, 1.7 Tg CH4 yr-1 higher compared to 1981-1990 due to a sea ice-induced, autumn-focused, warming. Since these results suggest a continued rise in methane emissions with future sea ice decline, observation programs need to include measurements during the autumn to further investigate the impact of this spatial connection on terrestrial methane emissions. PMID- 27667871 TI - Van Allen Probes observations of unusually low frequency whistler mode waves observed in association with moderate magnetic storms: Statistical study. AB - We show the first evidence for locally excited chorus at frequencies below 0.1 fce (electron cyclotron frequency) in the outer radiation belt. A statistical study of chorus during geomagnetic storms observed by the Van Allen Probes found that frequencies are often dramatically lower than expected. The frequency at peak power suddenly stops tracking the equatorial 0.5 fce and f/fce decreases rapidly, often to frequencies well below 0.1 fce (in situ and mapped to equator). These very low frequency waves are observed both when the satellites are close to the equatorial plane and at higher magnetic latitudes. Poynting flux is consistent with generation at the equator. Wave amplitudes can be up to 20 to 40 mV/m and 2 to 4 nT. We conclude that conditions during moderate to large storms can excite unusually low frequency chorus, which is resonant with more energetic electrons than typical chorus, with critical implications for understanding radiation belt evolution. PMID- 27667872 TI - The importance of rare, high-wind events for dust uplift in northern Africa. AB - Dust uplift is a nonlinear thresholded function of wind speed and therefore particularly sensitive to the long tails of observed wind speed probability density functions. This suggests that a few rare high-wind events can contribute substantially to annual dust emission. Here we quantify the relative roles of different wind speeds to dust-generating winds using surface synoptic observations of dust emission and wind from northern Africa. The results show that winds between 2 and 5 m s-1 above the threshold cause the most emission. Of the dust-generating winds, 25% is produced by very rare events occurring only at 0.1 to 1.4% of the time, depending on the region. Dust-producing winds are underestimated in ERA-I, since it misses the long tail found in observations. ERA I overpredicts (underpredicts) the frequency of emission strength winds in the southern (northern) regions. These problems cannot be solved by simple tunings. Finally, we show that rare events make the largest contribution to interannual variability in dust-generating winds and that ERA severely underestimates this interannual variability. PMID- 27667873 TI - Structure and composition of the neutral upper atmosphere of Mars from the MAVEN NGIMS investigation. AB - The Mars Atmosphere and Volatile EvolutioN (MAVEN) Neutral Gas and Ion Mass Spectrometer (NGIMS) provides sensitive detections of neutral gas and ambient ion composition. NGIMS measurements of nine atomic and molecular neutral species, and their variation with altitude, latitude, and solar zenith angle are reported over several months of operation of the MAVEN mission. Sampling NGIMS signals from multiple neutral species every several seconds reveals persistent and unexpectedly large amplitude density structures. The scale height temperatures are mapped over the course of the first few months of the mission from high down to midlatitudes. NGIMS measurements near the homopause of 40Ar/N2 ratios agree with those reported by the Sample Analysis at Mars investigation and allow the altitude of the homopause for the most abundant gases to be established. PMID- 27667874 TI - Mid-2000s North Atlantic shift: Heat budget and circulation changes. AB - Prior to the 2000s, the North Atlantic was the basin showing the greatest warming. However, since the mid-2000s during the so-called global warming hiatus, large amounts of heat were transferred in this basin from upper to deeper levels while the dominance in terms of atmospheric heat capture moved into the Indo Pacific. Here we show that a large transformation of modal waters in the eastern North Atlantic (ENA) played a crucial role in such contrasting behavior. First, strong winter mixing in 2005 transformed ENA modal waters into a much saltier, warmer, and denser variety, transferring upper ocean heat and salt gained slowly over time to deeper layers. The new denser waters also altered the zonal dynamic height gradient reversing the southward regional flow and enhancing the access of saltier southern waters to higher latitudes. Then, the excess salinity in northern regions favored additional heat injection through deep convection events in later years. PMID- 27667875 TI - An empirically based steady state friction law and implications for fault stability. AB - Empirically based rate-and-state friction laws (RSFLs) have been proposed to model the dependence of friction forces with slip and time. The relevance of the RSFL for earthquake mechanics is that few constitutive parameters define critical conditions for fault stability (i.e., critical stiffness and frictional fault behavior). However, the RSFLs were determined from experiments conducted at subseismic slip rates (V < 1 cm/s), and their extrapolation to earthquake deformation conditions (V > 0.1 m/s) remains questionable on the basis of the experimental evidence of (1) large dynamic weakening and (2) activation of particular fault lubrication processes at seismic slip rates. Here we propose a modified RSFL (MFL) based on the review of a large published and unpublished data set of rock friction experiments performed with different testing machines. The MFL, valid at steady state conditions from subseismic to seismic slip rates (0.1 um/s < V < 3 m/s), describes the initiation of a substantial velocity weakening in the 1-20 cm/s range resulting in a critical stiffness increase that creates a peak of potential instability in that velocity regime. The MFL leads to a new definition of fault frictional stability with implications for slip event styles and relevance for models of seismic rupture nucleation, propagation, and arrest. PMID- 27667876 TI - Northward expansion of paddy rice in northeastern Asia during 2000-2014. AB - Paddy rice in monsoon Asia plays an important role in global food security and climate change. Here we documented annual dynamics of paddy rice areas in the northern frontier of Asia, including Northeastern (NE) China, North Korea, South Korea, and Japan, from 2000-2014 through analysis of satellite images. The paddy rice area has increased by 120% (2.5 to 5.5 million ha) in NE China, in comparison to a decrease in South Korea and Japan, and the paddy rice centroid shifted northward from 41.16 degrees N to 43.70 degrees N (~310 km) in this period. Market, technology, policy, and climate together drove the rice expansion in NE China. The increased use of greenhouse nurseries, improved rice cultivars, agricultural subsidy policy, and a rising rice price generally promoted northward paddy rice expansion. The potential effects of large rice expansion on climate change and ecological services should be paid more attention in the future. PMID- 27667877 TI - Annular modes and apparent eddy feedbacks in the Southern Hemisphere. AB - Lagged correlation analysis is often used to infer intraseasonal dynamical effects but is known to be affected by nonstationarity. We highlight a pronounced quasi 2 year peak in the anomalous zonal wind and eddy momentum flux convergence power spectra in the Southern Hemisphere, which is prima facie evidence for nonstationarity. We then investigate the consequences of this nonstationarity for the Southern Annular Mode and for eddy momentum flux convergence. We argue that positive lagged correlations previously attributed to the existence of an eddy feedback are more plausibly attributed to nonstationary interannual variability external to any potential feedback process in the midlatitude troposphere. The findings have implications for the diagnosis of feedbacks in both models and reanalysis data as well as for understanding the mechanisms underlying variations in the zonal wind. PMID- 27667878 TI - A novel method for expediting the development of patient-reported outcome measures and an evaluation across several populations. AB - Item response theory (IRT) models provide an appropriate alternative to the classical ordinal confirmatory factor analysis (CFA) during the development of patient-reported outcome measures (PROMs). Current literature has identified the assessment of IRT model fit as both challenging and underdeveloped (Sinharay & Johnson, 2003; Sinharay, Johnson, & Stern, 2006). This study evaluates the performance of Ordinal Bayesian Instrument Development (OBID), a Bayesian IRT model with a probit link function approach, through applications in two breast cancer-related instrument development studies. The primary focus is to investigate an appropriate method for comparing Bayesian IRT models in PROMs development. An exact Bayesian leave-one-out cross-validation (LOO-CV) approach (Vehtari & Lampinen, 2002) is implemented to assess prior selection for the item discrimination parameter in the IRT model and subject content experts' bias (in a statistical sense and not to be confused with psychometric bias as in differential item functioning) toward the estimation of item-to-domain correlations. Results support the utilization of content subject experts' information in establishing evidence for construct validity when sample size is small. However, the incorporation of subject experts' content information in the OBID approach can be sensitive to the level of expertise of the recruited experts. More stringent efforts need to be invested in the appropriate selection of subject experts to efficiently use the OBID approach and reduce potential bias during PROMs development. PMID- 27667879 TI - Emotion talk in the context of young people self-harming: facing the feelings in family therapy. AB - : This article describes the use of emotion talk in the context of using a manualised approach to family therapy where the presenting problem is self-harm. Whilst we understand that there is an internal aspect to emotion, we also consider emotions to be socially purposeful, culturally constructed and interactional. We found that within the presenting families, negative emotions were often talked about as located within the young person. Through using 'emotion talk' (Fredman, 2004) in deconstructing and tracking emotions and exploring how emotions connected to family-of-origin and cultural contexts, we developed an interactional understanding of these emotions. This led to better emotional regulation within the family and offered alternative ways of relating. The article discusses the use of relational reflexivity, and using the therapist and team's emotions to enable the therapeutic process, encouraging reflexivity on the self of the therapist in relation to work with emotions. PRACTITIONER POINTS: Emotions can be seen as both a reflection of feelings experienced by the individual and as a communication.An interactional understanding of emotions can be used therapeutically.Therapists should explore emotional displays and track the interactional patterns within the therapeutic system.Therapists should self reflexive about ways of doing emotions and use this awareness in practice. PMID- 27667880 TI - Robust inference for the Two-Sample 2SLS estimator. AB - The Two-Sample Two-Stage Least Squares (TS2SLS) data combination estimator is a popular estimator for the parameters in linear models when not all variables are observed jointly in one single data set. Although the limiting normal distribution has been established, the asymptotic variance formula has only been stated explicitly in the literature for the case of conditional homoskedasticity. By using the fact that the TS2SLS estimator is a function of reduced form and first-stage OLS estimators, we derive the variance of the limiting normal distribution under conditional heteroskedasticity. A robust variance estimator is obtained, which generalises to cases with more general patterns of variable (non )availability. Stata code and some Monte Carlo results are provided in an Appendix. Stata code for a nonlinear GMM estimator that is identical to the TS2SLS estimator in just identified models and asymptotically equivalent to the TS2SLS estimator in overidentified models is also provided there. PMID- 27667881 TI - A note on modeling sparse exponential-family functional response curves. AB - Non-Gaussian functional data are considered and modeling through functional principal components analysis (FPCA) is discussed. The direct extension of popular FPCA techniques to the generalized case incorrectly uses a marginal mean estimate for a model that has an inherently conditional interpretation, and thus leads to biased estimates of population and subject-level effects. The methods proposed address this shortcoming by using either a two-stage or joint estimation strategy. The performance of all methods is compared numerically in simulations. An application to ambulatory heart rate monitoring is used to further illustrate the distinctions between approaches. PMID- 27667882 TI - Normal-Gamma-Bernoulli Peak Detection for Analysis of Comprehensive Two Dimensional Gas Chromatography Mass Spectrometry Data. AB - Compared to other analytical platforms, comprehensive two-dimensional gas chromatography coupled with mass spectrometry (GC*GC-MS) has much increased separation power for analysis of complex samples and thus is increasingly used in metabolomics for biomarker discovery. However, accurate peak detection remains a bottleneck for wide applications of GC*GC-MS. Therefore, the normal-exponential Bernoulli (NEB) model is generalized by gamma distribution and a new peak detection algorithm using the normal-gamma-Bernoulli (NGB) model is developed. Unlike the NEB model, the NGB model has no closed-form analytical solution, hampering its practical use in peak detection. To circumvent this difficulty, three numerical approaches, which are fast Fourier transform (FFT), the first order and the second-order delta methods (D1 and D2), are introduced. The applications to simulated data and two real GC*GC-MS data sets show that the NGB D1 method performs the best in terms of both computational expense and peak detection performance. PMID- 27667883 TI - Porcine lie detectors: Automatic quantification of posture state and transitions in sows using inertial sensors. AB - This paper presents a novel approach to automated classification and quantification of sow postures and posture transitions that may enable large scale and accurate continuous behaviour assessment on farm. Automatic classification and quantification of postures and posture transitions in domestic animals has substantial potential to enhance their welfare and productivity. Analysis of such behaviours in farrowing sows can highlight the need for human intervention or lead to the prediction of movement patterns that are potentially dangerous for their piglets, such as crushing when the sow lies down. Data were recorded by a tri-axial accelerometer secured to the hind-end of each sow, in a deployment that involved six sows over the period around parturition. The posture state (standing, sitting, lateral and sternal lying) was automatically classified for the full dataset with a mean F1 score (a measure of predictive performance between 0 and 1) of 0.78. Sitting was shown to present a greater challenge to classification with a F1 score of 0.54, compared to the lateral lying postures, which were classified with an average F1 score of 0.91. Posture transitions were detected with a F1 score of 0.79. We automatically extracted and visualized a range of features that characterise the manner in which the sows changed posture in order to provide comparative descriptors of sow activity and lying style that can be used to assess the influence of genetics or housing design. The methodology presented in this paper can be applied in large scale deployments with potential for enhancing animal welfare and productivity on farm. PMID- 27667884 TI - A new silicon tracker for proton imaging and dosimetry. AB - For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction around the world today. The Proton Radiotherapy, Verification and Dosimetry Applications (PRaVDA) consortium are developing instrumentation for particle therapy based upon technology from high-energy physics. The characteristics of a new silicon micro-strip tracker for particle therapy will be presented. The array uses specifically designed, large area sensors with technology choices that follow closely those taken for the ATLAS experiment at the HL-LHC. These detectors will be arranged into four units each with three layers in an x-u-v configuration to be suitable for fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of tracing the path of ~200 MeV protons entering and exiting a patient allowing a new mode of imaging known as proton computed tomography (pCT). This will aid the accurate delivery of treatment doses and in addition, the tracker will also be used to monitor the beam profile and total dose delivered during the high fluences used for treatment. We present here details of the design, construction and assembly of one of the four units that will make up the complete tracker along with its characterisation using radiation tests carried out using a 90Sr source in the laboratory and a 60 MeV proton beam at the Clatterbridge Cancer Centre. PMID- 27667885 TI - Preschool Education, Educational Attainment, and Crime Prevention: Contributions of Cognitive and Non-Cognitive Skills. AB - We investigated the extent to which cognitive and noncognitive skills accounted for the measured links between participation in preschool intervention and high school completion, highest grade completed, and incarceration history in early adulthood. Using data from the Chicago Longitudinal Study, an on-going 20-year investigation of the effects of the school-based Child-Parent Center early intervention program for over 1,500 children, we assessed the contribution of school readiness and achievement test scores up to age 14 and remedial education as well as measures of social adjustment, motivation, educational expectations, problem behavior, and juvenile arrest to the estimated direct effect of preschool. Hierarchical regression analysis indicated that when assessed separately, cognitive factors accounted for 42% of the preschool effect on high school completion, 37% on highest grade completed, and 23% on incarceration history by age 24 while noncognitive factors accounted for, respectively, 36%, 45%, and 59%. Together, cognitive and noncognitive factors explained 46%, 51%, and 59% of the main effect of preschool participation. The set of cognitive skills made greater value-added contributions to educational attainment while noncognitive skills made greater value-added contributions to incarceration history. Our findings support the important role of test scores, school performance, and social and motivational factors in explaining the effect of preschool participation on economically important indicators of well-being. PMID- 27667887 TI - Preschool-to-Third Grade Programs and Practices: A Review of Research. AB - The preschool-to-third grade perspective has helped the early childhood field move away from a reliance on relatively brief or one-shot programs toward more systematic and comprehensive models that span most of children's first decade. We review the knowledge base on the effectiveness of preschool to third grade intervention programs and practices for young children making the transition to school. Our coverage includes extended early childhood interventions, preschool programs, full-day kindergarten, reduced class sizes in the early grades, parent involvement, instructional practices, and school transitions (mobility). We distinguish between two major PK-3 strategies. PK-3 programs are planned interventions that begin during any of the five years of a child's life before kindergarten and which continue up to third grade. The most comprehensive programs include all these elements, and serve children from low-income families or who have special needs. Alternatively, PK-3 practices are defined as specific elements or components of extended early childhood programs that are hypothesized to be associated with children's outcomes. These elements may include preschool education, full-day kindergarten, reduced class sizes, teaching practices, and parent involvement activities. Overall, we find growing evidence for the positive effects of PK-3 programs and practices. The strongest evidence supporting enduring effects into adulthood is from center-based preschool programs followed by small classes in the early grades. Additional longitudinal studies are needed into adulthood to fully document the effects of different PK-3 programs and to verify the extent to which PK-3 practices (e.g., parent involvement, school mobility) have long-term effects into adulthood. PMID- 27667886 TI - Comparing early adult outcomes of maltreated and non-maltreated children: A prospective longitudinal investigation. AB - Using prospective data from the Chicago Longitudinal Study, this investigation examined associations between child maltreatment and an array of outcomes in early adulthood. Findings from bivariate and multivariate analyses indicated that verified maltreatment victims fared significantly worse than participants without an indicated maltreatment report on indicators of educational and economic attainment, criminal offending, and behavioral and mental health. Results also revealed that, while many maltreated children appeared to function well on individual outcomes, a large majority did not achieve criteria for resilience when development was assessed across domains. For example, non-maltreated participants were more than twice as likely to attain five or more positive outcomes (38.2%) on an aggregate seven-item index as the maltreated group (15.7%). These findings suggest that child maltreatment is associated with extensive and enduring impacts, reinforcing the need to develop and implement effective maltreatment prevention and intervention strategies. PMID- 27667888 TI - Patterns of Enrollment and Engagement of Custodial Grandmothers in a Randomized Clinical Trial of Psychoeducational Interventions. AB - The authors used Andersen's (2008) behavior model to investigate patterns of enrollment and treatment engagement among 343 custodial grandmothers who participated in a randomized clinical trial of three psychosocial interventions:(a) a behavioral parenting program, (b) a cognitive behavioral coping program, or (c) an information-only condition. Treatment completion was superior to that typically found with birth parents, even though the grandmothers and their target grandchildren both had high levels of mental and physical health challenges. Compliance did not differ significantly by condition but was higher among grandmothers who self-reported less positive affect, were older, and were using mental health professionals. Treatment satisfaction was highest in grandmothers who attended more treatment sessions, reported lower annual family income, had a health problem, and were using mental health professionals. The practice and policy implications of these findings are discussed, especially in terms of strategies for enhancing the engagement of custodial grandfamilies in future psychoeducational interventions. PMID- 27667889 TI - Prospective Analyses of Childhood Factors and Antisocial Behavior for Students with High-Incidence Disabilities. PMID- 27667891 TI - A mixed valence zinc dithiolene system with spectator metal and reactor ligands. AB - Neutral complexes of zinc with N,N'-diisopropylpiperazine-2,3-dithione ( i Pr2Dt0) and N,N'-dimethylpiperazine-2,3-dithione (Me2Dt0) with chloride or maleonitriledithiolate (mnt2-) as coligands have been synthesized and characterized. The molecular structures of these zinc complexes have been determined using single crystal X-ray diffractometry. Complexes recrystallize in monoclinic P type systems with zinc adopting a distorted tetrahedral geometry. Two zinc complexes with mixed-valent dithiolene ligands exhibit ligand-to-ligand charge transfer bands. Optimized geometries, molecular vibrations and electronic structures of charge-transfer complexes were calculated using density functional theory (B3LYP/6-311G+(d,p) level). Redox orbitals are shown to be almost exclusively ligand in nature, with a HOMO based heavily on the electron-rich maleonitriledithiolate ligand, and a LUMO comprised mostly of the electron deficient dithione ligand. Charge transfer is thus believed to proceed from dithiolate HOMO to dithione LUMO, showing ligand-to-ligand redox interplay across a d10 metal. PMID- 27667890 TI - A review of the impacts of degradation threats on soil properties in the UK. AB - National governments are becoming increasingly aware of the importance of their soil resources and are shaping strategies accordingly. Implicit in any such strategy is that degradation threats and their potential effect on important soil properties and functions are defined and understood. In this paper, we aimed to review the principal degradation threats on important soil properties in the UK, seeking quantitative data where possible. Soil erosion results in the removal of important topsoil and, with it, nutrients, C and porosity. A decline in soil organic matter principally affects soil biological and microbiological properties, but also impacts on soil physical properties because of the link with soil structure. Soil contamination affects soil chemical properties, affecting nutrient availability and degrading microbial properties, whilst soil compaction degrades the soil pore network. Soil sealing removes the link between the soil and most of the 'spheres', significantly affecting hydrological and microbial functions, and soils on re-developed brownfield sites are typically degraded in most soil properties. Having synthesized the literature on the impact on soil properties, we discuss potential subsequent impacts on the important soil functions, including food and fibre production, storage of water and C, support for biodiversity, and protection of cultural and archaeological heritage. Looking forward, we suggest a twin approach of field-based monitoring supported by controlled laboratory experimentation to improve our mechanistic understanding of soils. This would enable us to better predict future impacts of degradation processes, including climate change, on soil properties and functions so that we may manage soil resources sustainably. PMID- 27667893 TI - Increased Serum Level of MicroRNA-663 Is Correlated with Poor Prognosis of Patients with Nasopharyngeal Carcinoma. AB - MicroRNAs (miRs) play crucial roles in the carcinogenesis and malignant progression of human cancers including nasopharyngeal carcinoma (NPC). In this study, we aimed to investigate the association of serum miR-663 levels with the clinical factors and prognosis of NPC patients. Real-time PCR was performed to examine the amount of miR-663 in serum in NPC patients and healthy controls. Our data showed that the amount of miR-663 in serum was significantly higher in NPC patients than in healthy controls. Moreover, the serum levels of miR-663 were significantly correlated with the grade, lymph node metastasis, and clinical stage of NPC. Furthermore, higher serum miR-663 levels were closely associated with worse 5-year overall survival (OS) and relapse-free survival (RFS) of patients with NPC, and the serum level of miR-663 was found to be an independent predicator for the prognosis of NPC. In addition, after receiving chemoradiotherapy, the serum levels of miR-663 were significantly reduced in NPC patients. In summary, miR-663 was upregulated in the serum of NPC patients, which was downregulated after chemoradiotherapy, and its increased levels were closely associated with malignant progression and poor prognosis in NPC patients. Therefore, the amount of miR-663 in serum may become a potential predicator for the clinical outcome of NPC patients. PMID- 27667894 TI - Local Composite Quantile Regression Smoothing for Harris Recurrent Markov Processes. AB - In this paper, we study the local polynomial composite quantile regression (CQR) smoothing method for the nonlinear and nonparametric models under the Harris recurrent Markov chain framework. The local polynomial CQR regression method is a robust alternative to the widely-used local polynomial method, and has been well studied in stationary time series. In this paper, we relax the stationarity restriction on the model, and allow that the regressors are generated by a general Harris recurrent Markov process which includes both the stationary (positive recurrent) and nonstationary (null recurrent) cases. Under some mild conditions, we establish the asymptotic theory for the proposed local polynomial CQR estimator of the mean regression function, and show that the convergence rate for the estimator in nonstationary case is slower than that in stationary case. Furthermore, a weighted type local polynomial CQR estimator is provided to improve the estimation efficiency, and a data-driven bandwidth selection is introduced to choose the optimal bandwidth involved in the nonparametric estimators. Finally, we give some numerical studies to examine the finite sample performance of the developed methodology and theory. PMID- 27667896 TI - Third Party Interaction in the Medical Context: Code-switching and Control. AB - The purpose of this paper is to examine the micro-interactional co-construction of power within Spanish language concordant medical consultations in California involving a third party family member. Findings indicate the third party instigates code-switching to English on the part of medical providers, a language that the patient does not understand, rendering the patient a non-participant in the medical consultation. In these consultations involving a third party family member, monolingual Spanish-speaking patients are stripped of control in ways that are similar to other powerless groups in medical consultations. Implications include the need to further examine how micro-level interactions reproduce societal ideologies and shape policy on the ground. PMID- 27667892 TI - Proteomic Biomarkers Panel: New Insights in Chronic Kidney Disease. AB - Chronic kidney disease, despite being a "silent epidemic" disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients. The specific objective of our study was to characterize the relationship between the inflammatory status, the bone disorders markers, and kidney failure in chronic kidney disease patient stages 2-4, in order to design a novel biomarker panel that improves early disease diagnosis and therapeutic response, thus being further integrated into clinical applications. A panel of proteomic biomarkers, assessed by xMAP array, which includes mediators of inflammation (IL-6, TNF alpha) and mineral and bone disorder biomarkers (OPG, OPN, OCN, FGF-23, and Fetuin-A), was found to be more relevant than a single biomarker to detect early CKD stages. The association between inflammatory cytokines and bone disorders markers, IL-6, TNF-alpha, OPN, OPG, and FGF-23, reflects the severity of vascular changes in CKD and predicts disease progression. Proteomic xMAP analyses shed light on a new approach to clinical evaluation for CKD staging and prognosis. PMID- 27667895 TI - A semivarying joint model for longitudinal binary and continuous outcomes. AB - Semivarying models extend varying coefficient models by allowing some regression coefficients to be constant with respect to the underlying covariate(s). In this paper we develop a semivarying joint modelling framework for estimating the time varying association between two intensively measured longitudinal response: a continuous one and a binary one. To overcome the major challenge of jointly modelling these responses, namely, the lack of a natural multivariate distribution, we introduce a Gaussian latent variable underlying the binary response. Then we decompose the model into two components: a marginal model for the continuous response, and a conditional model for the binary response given the continuous response. We develop a two-stage estimation procedure and discuss the asymptotic normality of the resulting estimators. We assess the finite-sample performance of our procedure using a simulation study, and we illustrate our method by analyzing binary and continuous responses from the Women's Interagency HIV Study. PMID- 27667897 TI - [EFFECTIVE EDUCATIONAL INTERVENTIONS IN HIV FOR WOMEN]. AB - : In Chile, it is estimated that over 38,000 people live with Human Immunodeficiency Virus [HIV]. In 2001, there were 1092 Chilean women living with HIV, and in 2006 there were 7,600, further affecting low income populations. These findings reveal the necessity to create prevention strategies directed towards Chilean women. OBJECTIVE: the purpose of this revision is to analyze studies of prevention programs in HIV in order to determine what aspects should be included in successful HIV prevention programs with women. DESIGN AND METHOD: a literature review was carried out using searches done in the databases Proquest and CINAHL, Pubmed and Scielo. The search was limited by the criteria of full text only, within the last ten years and free access, written in Spanish or English. Fifteen articles were selected for the following revision. RESULTS: all of the selected articles measured the effect of an intervention on knowledge and behaviours related to HIV/AIDS. Fourteen articles produced significant changes in positive behaviours or knowledge related to the prevention of HIV. CONCLUSIONS: prevention programs in HIV with socially disadvantaged women can be effective in provoking changes in behaviours and knowledge associated with HIV. Successful interventions were those based on prevention theories or models of behavior change and adapted to the culture of the sample. PMID- 27667898 TI - Accuracy in the Diagnosis of the Mental Nerve Loop. A Comparative Study Between Panoramic Radiography and Cone Beam Computed Tomography. AB - Dental implant and chin osteotomy are executed on the mandible body and the mental nerve is an important anatomical limit. The aim of this research was to know the position of the mental nerve loop comparing result in panoramic radiography and cone beam computed tomography. We analyzed 94 hemimandibles and the patient sample comprised female and male subjects of ages ranging from 18 to 52 years (mean age, 35 years) selected randomly from the database of patients at the Division of Oral Radiology at Piracicaba Dental School State University of Campinas; the anterior loop (AL) of the mental nerve was evaluated regarding the presence or absence, which was classified as rectilinear or curvilinear and measurement of its length was obtained. The observations were made in the digital panoramic radiography (PR) and the cone beam computed tomography (CBCT) according to a routine technique. The frequencies of the AL identified through PR and CBCT were different: in PR the loop was identified in 42.6% of cases, and only 12.8% were bilateral. In contrast, the AL was detected in 29.8% of the samples using CBCT, with 6.4% being bilateral; Statistical comparison between PR and CBCT showed that the PR led to false-positive diagnosis of the AL in this sample. According to the results of this study, the frequency of AL is low. Thus, it can be assumed that it is not a common condition in this population. PMID- 27667900 TI - A modified expression of the major hydrolase activator in Hypocrea jecorina (Trichoderma reesei) changes enzymatic catalysis of biopolymer degradation. AB - Hypocrea jecorina (anamorph Trichoderma reesei) is a saprophytic fungus that produces hydrolases, which are applied in different types of industries and used for the production of biofuel. A recombinant Hypocrea strain, which constantly expresses the main transcription activator of hydrolases (Xylanase regulator 1), was found to grow faster on xylan and its monomeric backbone molecule d-xylose. This strain also showed improved ability of clearing xylan medium on plates. Furthermore, this strain has a changed transcription profile concerning genes encoding for hydrolases and enzymes associated with degradation of (hemi)celluloses. We demonstrated that enzymes of this strain from a xylan cultivation favoured break down of hemicelluloses to the monomer d-xylose compared to the parental strain, while the enzymes of the latter one formed more xylobiose. Applying supernatants from cultivation on carboxymethylcellulose in enzymatic conversion of hemicelluloses, the enzymes of the recombinant strain were clearly producing more of both, d-xylose and xylobiose, compared to the parental strain. Altogether, these results point to a changed hydrolase expression profile, an enhanced capability to form the xylan-monomer d-xylose and the assumption that there is a disordered induction pattern if the Xylanase regulator 1 is de-regulated in Hypocrea. PMID- 27667899 TI - Grammatical Constraints on Language Switching: Language Control is not Just Executive Control. AB - The current study investigated the roles of grammaticality and executive control on bilingual language selection by examining production speed and failures of language control, or intrusion errors (e.g., saying el instead of the), in young and aging bilinguals. Production of mixed-language connected speech was elicited by asking Spanish-English bilinguals to read aloud paragraphs that had mostly grammatical (conforming to naturally occurring constraints) or mostly ungrammatical (haphazard mixing) language switches, and low or high switching rate. Mixed-language speech was slower and less accurate when switch-rate was high, but especially (for speed) or only (for intrusion errors) if switches were also ungrammatical. Executive function ability (measured with a variety of tasks in young bilinguals in Experiment 1, and aging bilinguals in Experiment 2), slowed production and increased intrusion rate in a generalized fashion, but with little or no interaction with grammaticality. Aging effects appeared to reflect reduced monitoring ability (evidenced by a lower rate of self-corrected intrusions). These results demonstrate robust effects of grammatical encoding on language selection, and imply that executive control influences bilingual language production only after sentence planning and lexical selection. PMID- 27667901 TI - Mapping paddy rice planting areas through time series analysis of MODIS land surface temperature and vegetation index data. AB - Knowledge of the area and spatial distribution of paddy rice is important for assessment of food security, management of water resources, and estimation of greenhouse gas (methane) emissions. Paddy rice agriculture has expanded rapidly in northeastern China in the last decade, but there are no updated maps of paddy rice fields in the region. Existing algorithms for identifying paddy rice fields are based on the unique physical features of paddy rice during the flooding and transplanting phases and use vegetation indices that are sensitive to the dynamics of the canopy and surface water content. However, the flooding phenomena in high latitude area could also be from spring snowmelt flooding. We used land surface temperature (LST) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor to determine the temporal window of flooding and rice transplantation over a year to improve the existing phenology-based approach. Other land cover types (e.g., evergreen vegetation, permanent water bodies, and sparse vegetation) with potential influences on paddy rice identification were removed (masked out) due to their different temporal profiles. The accuracy assessment using high-resolution images showed that the resultant MODIS-derived paddy rice map of northeastern China in 2010 had a high accuracy (producer and user accuracies of 92% and 96%, respectively). The MODIS based map also had a comparable accuracy to the 2010 Landsat-based National Land Cover Dataset (NLCD) of China in terms of both area and spatial pattern. This study demonstrated that our improved algorithm by using both thermal and optical MODIS data, provides a robust, simple and automated approach to identify and map paddy rice fields in temperate and cold temperate zones, the northern frontier of rice planting. PMID- 27667902 TI - The University Experiences of Students with Learning Disabilities. AB - To explore the university experiences of students with learning disabilities (LD), 63,802 responses to the 2014 Student Experience in the Research University Survey were analyzed. Compared to other students, those with self-reported LD (5.96%) had difficulty with assignments and had more obstacles caused by non academic responsibilities and imposed by their skill levels. Students with self reported LD sensed more bias towards people with disabilities on campus, and they were less satisfied with their overall experience. Interactions between disability status and age suggested even more challenges for older students who self-reported LD. Approximately one-third of students who self-reported LD received accommodations. The rate of accommodations was higher among individuals who were wealthy, who lived alone, and who were out-of-state students. Compared to students who self-reported LD but reported no accommodations, those with accommodations had more contact with faculty and less difficulty with assignments. PMID- 27667903 TI - Enforcement of entailment constraints in distributed service-based business processes. AB - CONTEXT: A distributed business process is executed in a distributed computing environment. The service-oriented architecture (SOA) paradigm is a popular option for the integration of software services and execution of distributed business processes. Entailment constraints, such as mutual exclusion and binding constraints, are important means to control process execution. Mutually exclusive tasks result from the division of powerful rights and responsibilities to prevent fraud and abuse. In contrast, binding constraints define that a subject who performed one task must also perform the corresponding bound task(s). OBJECTIVE: We aim to provide a model-driven approach for the specification and enforcement of task-based entailment constraints in distributed service-based business processes. METHOD: Based on a generic metamodel, we define a domain-specific language (DSL) that maps the different modeling-level artifacts to the implementation-level. The DSL integrates elements from role-based access control (RBAC) with the tasks that are performed in a business process. Process definitions are annotated using the DSL, and our software platform uses automated model transformations to produce executable WS-BPEL specifications which enforce the entailment constraints. We evaluate the impact of constraint enforcement on runtime performance for five selected service-based processes from existing literature. RESULTS: Our evaluation demonstrates that the approach correctly enforces task-based entailment constraints at runtime. The performance experiments illustrate that the runtime enforcement operates with an overhead that scales well up to the order of several ten thousand logged invocations. Using our DSL annotations, the user-defined process definition remains declarative and clean of security enforcement code. CONCLUSION: Our approach decouples the concerns of (non-technical) domain experts from technical details of entailment constraint enforcement. The developed framework integrates seamlessly with WS-BPEL and the Web services technology stack. Our prototype implementation shows the feasibility of the approach, and the evaluation points to future work and further performance optimizations. PMID- 27667904 TI - Gender differences in developmental dyscalculia depend on diagnostic criteria. AB - Developmental dyscalculia (DD) is a learning difficulty specific to mathematics learning. The prevalence of DD may be equivalent to that of dyslexia, posing an important challenge for effective educational provision. Nevertheless, there is no agreed definition of DD and there are controversies surrounding cutoff decisions, specificity and gender differences. In the current study, 1004 British primary school children completed mathematics and reading assessments. The prevalence of DD and gender ratio were estimated in this sample using different criteria. When using absolute thresholds, the prevalence of DD was the same for both genders regardless of the cutoff criteria applied, however gender differences emerged when using a mathematics-reading discrepancy definition. Correlations between mathematics performance and the control measures selected to identify a specific learning difficulty affect both prevalence estimates and whether a gender difference is in fact identified. Educational implications are discussed. PMID- 27667905 TI - Straw use and availability for second generation biofuels in England. AB - Meeting EU targets for renewable transport fuels by 2020 will necessitate a large increase in bioenergy feedstocks. Although deployment of first generation biofuels has been the major response to meeting these targets they are subject to wide debate on their sustainability leading to the development of second generation technologies which use lignocellulosic feedstocks. Second generation biofuel can be subdivided into those from dedicated bioenergy crops (DESGB), e.g. miscanthus, or those from co-products (CPSGB) such as cereal straw. Potential supply of cereal straw as a feedstock for CPSGB's is uncertain in England due to the difficulty in obtaining data and the uncertainty in current estimates. An on farm survey of 249 farms (Cereal, General Cropping and Mixed) in England was performed and linked with Farm Business Survey data to estimate current straw use and potential straw availability. No significant correlations between harvested grain and straw yields were found for wheat and oilseed rape and only a weak correlation was observed for barley. In England there is a potential cereal straw supply of 5.27 Mt from arable farm types; 3.82 Mt are currently used and 1.45 Mt currently chopped and incorporated. If currently chopped and incorporated cereal straw from arable farm types was converted into bioethanol, this could represent 1.5% of the UK petrol consumption by energy equivalence. The variations in regional straw yields (t ha-1) have a great effect on the England supply of straw and the potential amount of bioethanol that can be produced. PMID- 27667907 TI - Partial linear varying multi-index coefficient model for integrative gene environment interactions. AB - Gene-environment (G*E) interactions play key roles in many complex diseases. An increasing number of epidemiological studies have shown the combined effect of multiple environmental exposures on disease risk. However, no appropriate statistical models have been developed to conduct a rigorous assessment of such combined effects when G*E interactions are considered. In this paper, we propose a partial linear varying multi-index coefficient model (PLVMICM) to assess how multiple environmental factors act jointly to modify individual genetic risk on complex disease. Our model includes the varying-index coefficient model as a special case, where discrete variables are admitted as the linear part. Thus PLVMICM allows one to study nonlinear interaction effects between genes and continuous environments as well as linear interactions between genes and discrete environments, simultaneously. We derive a profile method to estimate parametric parameters and a B-spline backfitted kernel method to estimate nonlinear interaction functions. Consistency and asymptotic normality of the parametric and nonparametric estimates are established under some regularity conditions. Hypothesis testing for the parametric coefficients and nonparametric functions are conducted. Results show that the statistics for testing the parametric coefficients and the non-parametric functions asymptotically follow a chi2 distribution with different degrees of freedom. The utility of the method is demonstrated through extensive simulations and a case study. PMID- 27667906 TI - The spindle assembly checkpoint: More than just keeping track of the spindle. AB - Genome stability is essential for cell proliferation and survival. Consequently, genome integrity is monitored by two major checkpoints, the DNA damage response (DDR) and the spindle assembly checkpoint (SAC). The DDR monitors DNA lesions in G1, S, and G2 stages of the cell cycle and the SAC ensures proper chromosome segregation in M phase. There have been extensive studies characterizing the roles of these checkpoints in response to the processes for which they are named; however, emerging evidence suggests significant crosstalk between the checkpoints. Here we review recent findings demonstrating overlapping roles for the SAC and DDR in metaphase, and in response to DNA damage throughout the cell cycle. PMID- 27667908 TI - TIME-VARYING COEFFICIENT MODELS FOR JOINT MODELING BINARY AND CONTINUOUS OUTCOMES IN LONGITUDINAL DATA. AB - Motivated by an empirical analysis of ecological momentary assessment data (EMA) collected in a smoking cessation study, we propose a joint modeling technique for estimating the time-varying association between two intensively measured longitudinal responses: a continuous one and a binary one. A major challenge in joint modeling these responses is the lack of a multivariate distribution. We suggest introducing a normal latent variable underlying the binary response and factorizing the model into two components: a marginal model for the continuous response, and a conditional model for the binary response given the continuous response. We develop a two-stage estimation procedure and establish the asymptotic normality of the resulting estimators. We also derived the standard error formulas for estimated coefficients. We conduct a Monte Carlo simulation study to assess the finite sample performance of our procedure. The proposed method is illustrated by an empirical analysis of smoking cessation data, in which the question of interest is to investigate the association between urge to smoke, continuous response, and the status of alcohol use, the binary response, and how this association varies over time. PMID- 27667909 TI - Tuna and swordfish catch in the U.S. northwest Atlantic longline fishery in relation to mesoscale eddies. AB - To analyze the effects of mesoscale eddies, sea surface temperature (SST), and gear configuration on the catch of Atlantic bluefin (Thunnus thynnus), yellowfin (Thunnus albacares), and bigeye tuna (Thunnus obesus) and swordfish (Xiphias gladius) in the U.S. northwest Atlantic longline fishery, we constructed multivariate statistical models relating these variables to the catch of the four species in 62 121 longline hauls made between 1993 and 2005. During the same 13 year period, 103 anticyclonic eddies and 269 cyclonic eddies were detected by our algorithm in the region 30-55 degrees N, 30-80 degrees W. Our results show that tuna and swordfish catches were associated with different eddy structures. Bluefin tuna catch was highest in anticyclonic eddies whereas yellowfin and bigeye tuna catches were highest in cyclonic eddies. Swordfish catch was found preferentially in regions outside of eddies. Our study confirms that the common practice of targeting tuna with day sets and swordfish with night sets is effective. In addition, bluefin tuna and swordfish catches responded to most of the variables we tested in the opposite directions. Bluefin tuna catch was negatively correlated with longitude and the number of light sticks used whereas swordfish catch was positively correlated with these two variables. We argue that overfishing of bluefin tuna can be alleviated and that swordfish can be targeted more efficiently by avoiding fishing in anticyclonic eddies and in near-shore waters and using more light sticks and fishing at night in our study area, although further studies are needed to propose a solid oceanography-based management plan for catch selection. PMID- 27667910 TI - Laplace Variational Approximation for Semiparametric Regression in the Presence of Heteroskedastic Errors. AB - Variational approximations provide fast, deterministic alternatives to Markov Chain Monte Carlo for Bayesian inference on the parameters of complex, hierarchical models. Variational approximations are often limited in practicality in the absence of conjugate posterior distributions. Recent work has focused on the application of variational methods to models with only partial conjugacy, such as in semiparametric regression with heteroskedastic errors. Here, both the mean and log variance functions are modeled as smooth functions of covariates. For this problem, we derive a mean field variational approximation with an embedded Laplace approximation to account for the non-conjugate structure. Empirical results with simulated and real data show that our approximate method has significant computational advantages over traditional Markov Chain Monte Carlo; in this case, a delayed rejection adaptive Metropolis algorithm. The variational approximation is much faster and eliminates the need for tuning parameter selection, achieves good fits for both the mean and log variance functions, and reasonably reflects the posterior uncertainty. We apply the methods to log-intensity data from a small angle X-ray scattering experiment, in which properly accounting for the smooth heteroskedasticity leads to significant improvements in posterior inference for key physical characteristics of an organic molecule. PMID- 27667911 TI - 3D-printed external light trap for solar cells. AB - We present a universally applicable 3D-printed external light trap for enhanced absorption in solar cells. The macroscopic external light trap is placed at the sun-facing surface of the solar cell and retro-reflects the light that would otherwise escape. The light trap consists of a reflective parabolic concentrator placed on top of a reflective cage. Upon placement of the light trap, an improvement of 15% of both the photocurrent and the power conversion efficiency in a thin-film nanocrystalline silicon (nc-Si:H) solar cell is measured. The trapped light traverses the solar cell several times within the reflective cage thereby increasing the total absorption in the cell. Consequently, the trap reduces optical losses and enhances the absorption over the entire spectrum. The components of the light trap are 3D printed and made of smoothened, silver-coated thermoplastic. In contrast to conventional light trapping methods, external light trapping leaves the material quality and the electrical properties of the solar cell unaffected. To explain the theoretical operation of the external light trap, we introduce a model that predicts the absorption enhancement in the solar cell by the external light trap. The corresponding calculated path length enhancement shows good agreement with the empirically derived value from the opto-electrical data of the solar cell. Moreover, we analyze the influence of the angle of incidence on the parasitic absorptance to obtain full understanding of the trap performance. (c) 2015 The Authors. Progress in Photovoltaics: Research and Applications published by John Wiley & Sons, Ltd. PMID- 27667912 TI - Surrounding community residents' expectations of HOPE VI for their community, health and physical activity. AB - Using a community-engaged participatory research approach, this study identified surrounding community residents' expectations for how a HOPE VI housing initiative might affect their community and individual health and physical activity. Fifty-nine women and men engaged in concept mapping, which is a mixed methods approach, where participants generate, sort, and rate ideas. Participants generated 197 unique statements. Thirteen thematic clusters related to expected changes for the community, health and physical activity emerged. Residents' rated 'Increased Pride in the Neighborhood' and 'Increased Safety' as the most important factors related to HOPE VI whereas 'Drawbacks of HOPE VI' was rated as least important. This research provides insight into the potential impacts of housing initiatives from the perspective of those most affected by such initiatives. The findings also highlight environmental changes as potential mechanisms that may improve residents' perceptions of the community and encourage healthy lifestyles. PMID- 27667913 TI - First 101 Robotic General Surgery Cases in a Community Hospital. AB - BACKGROUND AND OBJECTIVES: The general surgeon's robotic learning curve may improve if the experience is classified into categories based on the complexity of the procedures in a small community hospital. The intraoperative time should decrease and the incidence of complications should be comparable to conventional laparoscopy. The learning curve of a single robotic general surgeon in a small community hospital using the da Vinci S platform was analyzed. METHODS: Measured parameters were operative time, console time, conversion rates, complications, surgical site infections (SSIs), surgical site occurrences (SSOs), length of stay, and patient demographics. RESULTS: Between March 2014 and August 2015, 101 robotic general surgery cases were performed by a single surgeon in a 266-bed community hospital, including laparoscopic cholecystectomies, inguinal hernia repairs; ventral, incisional, and umbilical hernia repairs; and colorectal, foregut, bariatric, and miscellaneous procedures. Ninety-nine of the cases were completed robotically. Seven patients were readmitted within 30 days. There were 8 complications (7.92%). There were no mortalities and all complications were resolved with good outcomes. The mean operative time was 233.0 minutes. The mean console operative time was 117.6 minutes. CONCLUSION: A robotic general surgery program can be safely implemented in a small community hospital with extensive training of the surgical team through basic robotic skills courses as well as supplemental educational experiences. Although the use of the robotic platform in general surgery could be limited to complex procedures such as foregut and colorectal surgery, it can also be safely used in a large variety of operations with results similar to those of conventional laparoscopy. PMID- 27667914 TI - Readmission Following Laparoscopic Sleeve Gastrectomy. AB - BACKGROUND AND OBJECTIVES: Prior studies have established a 1.7-4.33% readmission rate for laparoscopic sleeve gastrectomy (LSG), a rate that falls within the reported range for other bariatric procedures. The current report describes the incidence of 30-day readmission after primary LSG procedures performed at a single bariatric center of excellence (COE) and examines factors that may be associated with readmission. METHODS: Data on 343 consecutive LSG operations performed from February 2010 to May 2014 by a single surgeon (PG) were analyzed. Patients readmitted within 30 d were compared to the remaining patients by using Student's t test for continuous variables and the chi2 test for categorical variables. RESULTS: All LSGs were completed laparoscopically with no conversions to open procedures. There were no reoperations, leaks, perioperative hemorrhages, or mortalities. Twelve patients (3.5%) were readmitted; 1 was readmitted twice. There were no identified risk factors for readmission, including patient demographics, comorbidities, and perioperative factors. Notably, 7 (7%) readmissions occurred in the initial 100 patients and 5 (2%) in the remaining 243 patients (P = .04). Clinical pathways were modified after the initial 100 patients; routine contrast esophagograms were no longer performed, and a 1-day routine postoperative stay was adopted. Operative time also decreased from 94.2 +/- 23.8 to 78.2 +/- 20.0 min (P < .001). CONCLUSIONS: Readmission rates after LSG remain in a range similar to those described for other laparoscopic bariatric procedures. Larger prospective studies are needed to identify patterns of complications and readmissions in patients undergoing LSG that may differ from other bariatric procedures. PMID- 27667915 TI - Eye-Movement Control in RAN and Reading. AB - The present study examined the visual scanning hypothesis, which suggests that fluent oculomotor control is an important component underlying the predictive relationship between Rapid Automatized Naming (RAN) tasks and reading ability. Our approach was to isolate components of saccadic planning, articulation, and lexical retrieval in three modified RAN tasks. We analyzed two samples of undergraduate readers (age 17-27), we evaluated the incremental contributions of these components and found that saccadic planning to non-linguistic stimuli alone explained roughly one-third of the variance that conventional RAN tasks explained in eye-movements registered during text reading for comprehension. We conclude that the well-established predictive role of RAN for reading performance is in part due to the individual ability to coordinate rapid sequential eye-movements to visual non-linguistic stimuli. PMID- 27667916 TI - Bidirectional Relations between Text Reading Prosody and Reading Comprehension in the Upper Primary School Grades: A Longitudinal Perspective. AB - The purpose of this study was to examine the directionality of the relationship between text reading prosody and reading comprehension in the upper grades of primary school. We compared three theoretical possibilities: Two unidirectional relations from text reading prosody to reading comprehension and from reading comprehension to text reading prosody and a bidirectional relation between text reading prosody and reading comprehension. Further, we controlled for autoregressive effects and included decoding efficiency as a measure of general reading skill. Participants were 99 Dutch children, followed longitudinally, from fourth- to sixth-grade. Structural equation modeling showed that the bidirectional relation provided the best fitting model. In fifth-grade, text reading prosody was related to prior decoding and reading comprehension, whereas in sixth-grade, reading comprehension was related to prior text reading prosody. As such, the results suggest that the relation between text reading prosody and reading comprehension is reciprocal, but dependent on grade level. PMID- 27667918 TI - Effect of human milk as a treatment for dry eye syndrome in a mouse model. AB - PURPOSE: Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. METHODS: The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. RESULTS: Treatment with BAK reduced the mean corneal epithelial thickness from 36.77+/-0.64 MUm in the control mice to 21.29+/-3.2 MUm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2+/-2.5 MUm) or fat-reduced milk (36.1+/-1.58 MUm), outcomes that were similar to treatment with cyclosporine (38.52+/-2.47 MUm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76+/-1.78 MUm and 27.99+/-2.75 MUm, respectively), as were solvents used in the extraction of nopal materials (26.53+/-1.46 MUm for ethyl acetate, 21.59+/-5.87 MUm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to increase in eyes treated with nopal-derived materials. CONCLUSIONS: Whole and fat-reduced human milk showed promising effects in the prevention of BAK-induced loss of corneal epithelial thickness and epithelial damage in this mouse model. Further studies are required to determine whether human milk may be safely used to treat dry eye in patients. PMID- 27667920 TI - Dating furniture and coopered vessels without waney edge - Reconstructing historical wood-working in Austria with the help of dendrochronology. AB - In the present study, 208 furniture and 168 coopered vessels from three Austrian museums were examined. Dendrochronology was used to date objects and to extract further information such as the necessary time for seasoning, wood loss through wood-working and methods of construction. In most cases sampling was done by sanding the cross section and making digital photographs using a picture frame and measuring digitally. The dendrochronological dates of the sampled furniture range between 1524 and 1937. The group of furniture includes cupboards, chests, tables, benches, commodes and beds. In many cases furniture was artfully painted and sometimes even shows a painted year. With the help of dendrochronology it was proved that some objects had been painted for some time after construction, or had been over-painted. Most furniture, however, was painted immediately after completion. In this case, the seasoning and storage time of the boards and the wood loss due to shaping can be verified. As an average value, 14 years have passed between the dendrochronological date of the outermost ring and the painting. The time span includes time of seasoning and storage and the rings lost by wood-working. This leads, on the one hand to a short storage time of less than 10 years and on the other hand to very little wood loss due to manufacturing. Those boards being less shaped turned out to be back panels of cupboards, therefore they are recommended to be sampled for dating. Coopered vessels were dated between 1612 and 1940. There was evidence that staves were split and not sawn in many cases. The staves were often split out of the outermost part of the tree and hardly any wood was worked away which was proved by the close dendrochronological dates of the single staves of a vessel. Since there is a short time of storage and only little wood loss through wood-working, dating of objects without a waney edge becomes reasonable. PMID- 27667917 TI - Three-dimensional retinal organoids from mouse pluripotent stem cells mimic in vivo development with enhanced stratification and rod photoreceptor differentiation. AB - PURPOSE: The generation of three-dimensional (3D) organoids with optic cup-like structures from pluripotent stem cells has created opportunities for investigating mammalian retinal development in vitro. However, retinal organoids in culture do not completely reflect the developmental state and in vivo architecture of the rod-dominant mouse retina. The goals of this study were to develop an efficient protocol for generating retinal organoids from stem cells and examine the morphogenesis of rods in vitro. METHODS: To assess rod photoreceptor differentiation in retinal organoids, we took advantage of Nrl green fluorescent protein (GFP) mice that show rod-specific expression of GFP directed by the promoter of leucine zipper transcription factor NRL. Using embryonic and induced pluripotent stem cells (ESCs and iPSCs, respectively) derived from the Nrl-GFP mouse, we were successful in establishing long-term retinal organoid cultures using modified culture conditions (called High Efficiency Hypoxia Induced Generation of Photoreceptors in Retinal Organoids, or HIPRO). RESULTS: We demonstrated efficient differentiation of pluripotent stem cells to retinal structures. More than 70% of embryoid bodies formed optic vesicles at day (D) 7, >50% produced optic cups by D10, and most of them survived until at least D35. The HIPRO organoids included distinct inner retina neurons in a somewhat stratified architecture and mature Muller glia spanning the entire retina. Almost 70% of the cells in the retinal organoids were rod photoreceptors that exhibited elongated cilia. Transcriptome profiles of GFP+ rod photoreceptors, purified from organoids at D25-35, demonstrated a high correlation with the gene profiles of purified rods from the mouse retina at P2 to P6, indicating their early state of differentiation. CONCLUSIONS: The 3D retinal organoids, generated by HIPRO method, closely mimic in vivo retinogenesis and provide an efficient in vitro model to investigate photoreceptor development and modeling disease pathology. PMID- 27667919 TI - Relationship Characteristics Associated with Teen Dating Violence Perpetration. AB - Teen dating violence (TDV) is unstable across dating relationships, suggesting that characteristics of the relationship could be related to TDV. Few empirical studies have examined these links. This study examined associations between relationship characteristics and TDV perpetration among teens and sex differences in those associations. Relationship characteristics examined include tactics used to manipulate partners; ways of responding to relationship problems; relationship duration; exclusivity of the relationship; age difference between partners; and history of sexual intercourse with partner. Data were drawn from 667 teens in a current relationship (62.5% female and 81.4% white) enrolled in the 11th or 12th grade in 14 public schools in a rural US state. Bivariate and multivariable regression analyses examined proposed associations. 30.1% and 8.2% of teens reported controlling and physical TDV perpetration, respectively. In multivariable models, frequent use manipulation tactics increased risk for controlling or physical TDV perpetration. Teens dating a partner two or more years younger were at significantly increased risk for both controlling and physical perpetration. A significant interaction emerged between sex and exit/neglect accommodation for physical TDV. Characteristics of a current dating relationship play an important role in determining risk for controlling and physical TDV perpetration. PMID- 27667921 TI - Diversity and distribution of Chirostyloidea and Galatheoidea (Decapoda, Anomura) in the Southern Gulf of Mexico. AB - We examined the diversity, abundance, distribution, and average size of squat lobsters collected during eight cruises conducted on the continental shelf and slope of the Gulf of Mexico (Mexican/USA border to the Caribbean Sea). Six species belonging to two genera of Chirostyloidea, and 25 species of four genera of Galatheoidea are reported. A total of 1513 specimens were obtained of which 95 were Chirostylidae, two Galatheidae, 285 Munidopsidae, and 1131 Munididae. Of the species collected, 13.8% were only known from Caribbean Sea. Three species of Chirostylidae-Gastroptychus salvadori, Uroptychus capillatus, and Uroptychus spiniger-as well two of Munidopsidae, Munidopsis bradleyi and Munidopsis riveroi, are recorded for the first time in the Gulf of Mexico. The upper bathymetric range of one species and the lower one for eight species are extended. Biological and ecological traits of squat lobsters in the southern Gulf of Mexico are also provided. PMID- 27667922 TI - Description of a new species of Gaeolaelaps (Acari: Laelapidae) from Iran. AB - A new species of Gaeolaelaps (Acari, Mesostigmata, Laelapidae), Gaeolaelaps izajiensis sp. n. is described based on the morphological characters of adult females which were collected from soil sample in the Izeh and Ghaletol regions of the Khuzestan province, Iran. It can be distinguished from the other members of the genus by some morphological characteristics of dorsal shield, form and reticulation of epigynal shield, the exopodal plates, and the peritremes. PMID- 27667923 TI - Yamatochaitophorus yichunensis, a new species of aphid (Aphididae: Chaitophorinae) from northeast China. AB - Yamatochaitophorus yichunensis sp. n. is described from specimens collected in northeast China on Acer tegmentosum (Aceraceae). Yamatochaitophorus is also a new generic record for China. Type specimens are deposited in the National Zoological Museum of China, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (NZMC) and the Natural History Museum, London, UK (BMNH). PMID- 27667924 TI - Four new species of Gasteruption Latreille from NW China, with an illustrated key to the species from Palaearctic China (Hymenoptera, Gasteruptiidae). AB - Four new species of the genus Gasteruption Latreille, 1796 (Hymenoptera: Evanioidea: Gasteruptiidae: Gasteruptiinae) are reported from NW China: three from Shaanxi province and one from Ningxia province. The new species (Gasteruption bicoloratum Tan & van Achterberg, sp. n., Gasteruption huangshii Tan & van Achterberg, sp. n., Gasteruption pannuceum Tan & van Achterberg, sp. n., and Gasteruption shengi Tan & van Achterberg, sp. n.) and three newly recorded species (Gasteruption sinepunctatum Zhao, van Achterberg & Xu, 2012, Gasteruption boreale (Thomson, 1883) and Gasteruption oshimense Watanabe, 1924) are keyed and fully illustrated. In total, seven species are known from Shaanxi province, which is approximately half of the expected number. The East Palaearctic specimens provisionally identified as Gasteruption tournieri Schletterer, 1885, by Zhao et al. (2012) are included under Gasteruption oshimense Watanabe, 1924. PMID- 27667925 TI - Descriptions of a new species of Foenatopus Smith from China and the male of Parastephanellus brevicoxalis (Hymenoptera, Stephanidae). AB - A new species of the stephanid genus Foenatopus Smith, Foenatopus weii sp. n., is described and illustrated from Yunnan Province, China. A modified section of the identification key to species of Foenatopus is added to include the new species. The male of Parastephanellus brevicoxalis Hong, van Achterberg & Xu, 2011 from Guangdong Province, China is also described and illustrated for the first time. PMID- 27667926 TI - Two new species of Coleoxestia Aurivillius, 1912 from Brazil (Coleoptera, Cerambycidae, Cerambycinae, Cerambycini). AB - Two new species of Coleoxestia Aurivillius, 1912 are described from Brazil: Coleoxestia apeara, and Coleoxestia moromokoi. Both are included in a previous key. PMID- 27667927 TI - Molecular systematics of the Labeonini inhabiting the karst regions in southwest China (Teleostei, Cypriniformes). AB - The major phylogenetic pattern of the cyprinid tribe Labeonini has been revealed by previous molecular studies; however, the relationships within a clade that mainly inhabits the karst regions, which we refer to as the "karst group", in southwest China remain unresolved due to the low taxon sampling. This group includes more than 50% of the genera and species of Labeonini in China. Moreover, more than 90% of the genera of this group are endemic to China. In addition, some new genera and species of Labeonini have been discovered from these karst regions, but their taxonomic validity and phylogenetic position have not been examined. In this contribution, partial sequences of four nuclear (exon 3 of recombination activating protein 1, rhodopsin, early growth response protein 2B gene and interphotoreceptor retinoid binding protein gene) and three mitochondrial genes (cytochrome b, cytochrome oxidase subunit I and 16S ribosomal RNA) from 36 ingroup taxa and 25 outgroup taxa were analyzed to provide a hypothesis of the phylogenetic relationships within the labeonins of the karst regions in China. We propose that the monophyly of Parasinilabeo, Ptychidio, Rectoris and Semilabeo are supported. A new genus, Prolixicheilus, is erected for Pseudogyrinocheilus longisulcus. Cophecheilus bamen is the sister to Prolixicheilus longisulcus. Ptychidio, Pseudocrossocheilus, Semilabeo, Rectoris and Stenorynchoacrum are closely related with high support values. Sinocrossocheilus, Pseudogyrinocheilus, Paraqianlabeo, Hongshuia, Discogobio and Discocheilus form a clade together with high support. Considering molecular results and morphological differences, Parasinilabeo longicorpus and Ptychidio macrops might be the synonyms of Parasinilabeo assimilis and Ptychidio jordani respectively. Comprehensive taxonomic revisions of the two genera Parasinilabeo and Ptychidio may be necessary. PMID- 27667928 TI - The Middle Pleistocene vertebrate fauna from Khok Sung (Nakhon Ratchasima, Thailand): biochronological and paleobiogeographical implications. AB - The fluviatile terrace deposits of Khok Sung, Nakhon Ratchasima province, have yielded more than one thousand fossils, making this the richest Pleistocene vertebrate fauna of Thailand. The excellent preservation of the specimens allows precise characterization of the faunal composition. The mammalian fauna consists of fifteen species in thirteen genera, including a primate, a canid, a hyaenid, proboscideans, rhinoceroses, a suid, cervids, and bovids. Most species correspond to living taxa but globally (Stegodon cf. orientalis) and locally (Crocuta crocuta ultima, Rhinoceros unicornis, Sus barbatus, and Axis axis) extinct taxa were also present. The identification of Axis axis in Khok Sung, a chital currently restricted to the Indian Subcontinent, represents the first record of the species in Southeast Asia. Three reptilian taxa: Crocodylus cf. siamensis, Python sp., and Varanus sp., are also identified. Faunal correlations with other Southeast Asian sites suggest a late Middle to early Late Pleistocene age for the Khok Sung assemblage. However, the Khok Sung mammalian fauna is most similar to that of Thum Wiman Nakin, dated to older than 169 ka. The Khok Sung large mammal assemblage mostly comprises mainland Southeast Asian taxa that migrated to Java during the latest Middle Pleistocene, supporting the hypothesis that Thailand was a biogeographic pathway for the Sino-Malayan migration event from South China to Java. PMID- 27667929 TI - New species of Trophoniella from Shimoda, Japan (Annelida, Flabelligeridae). AB - Trophoniella hephaistos sp. n. was collected from a tank irrigated with seawater pumped directly from Nabeta Bay, Japan. This species is discriminated from other Trophoniella by having dorsal tubercles, a tongue-shaped branchial plate, a tunic covered with large sediment grains dorsally and ventrally, having eyes, and anchylosed neurohooks starting from chaetigers 17-20. This is the first record of Trophoniella from Japanese waters. Identification keys to species of Trophoniella and four gene sequences (COI, 16S, 18S, 28S) of this species are provided. Phylogenetic analysis was conducted to clarify phylogenetic position of Trophoniella in Flabelligeridae using four genes. PMID- 27667930 TI - A new species of Websterinereis from the Gulf of California and redescription of Websterinereis foli (Fauvel, 1930) (Annelida, Nereididae). AB - A new species of Websterinereis Pettibone, 1971, Websterinereis pettiboneae sp. n. is described from La Paz Bay, Gulf of California, Mexico. This species is similar to Websterinereis foli (Fauvel, 1930) in the neuropodial falcigers shape, but can be separated by the tentacular cirri length, notopodial prechaetal lobe shape, and the size of the notopodial dorsal and ventral ligules on posterior parapodia. Websterinereis foli is redescribed based upon type material. Additional observations on the inter-annual density variation of Websterinereis pettiboneae sp. n. during a four-year study are also provided. A key to all species of Websterinereis is included. PMID- 27667931 TI - Revision of Partulidae (Gastropoda, Stylommatophora) of Palau, with description of a new genus for an unusual ground-dwelling species. AB - We describe a new stylommatophoran land snail of the family Partulidae from Palau. The new species has a combination of morphological and ecological characters that do not allow its placement in any existing partulid genus, so we describe a new genus for it. The new genus is characterized by a large (18-23 mm) obese-pupoid shell; smooth protoconch; teleoconch with weak and inconsistent, progressively stronger, striae; last half of body whorl not extending beyond the penultimate whorl; widely expanded and reflexed peristome; relatively long penis, with longitudinal pilasters that fuse apically into a fleshy ridge that divides the main chamber from a small apical chamber; and vas deferens entering and penial-retractor muscle attaching at the apex of the penis. Unlike all other partulids, the new species is strictly associated with rocks in contact with the ground. Comparing the other three Palauan species - currently assigned to Partula - to our new genus and to other partulids makes it clear that they require their own genus because their morphology is quite different from that of true Partula and from that of all other genera. Hence, we resurrect the name Palaopartula Pilsbry for these snails. PMID- 27667932 TI - Sinocoelotes gen. n., a new genus of the subfamily Coelotinae (Araneae, Agelenidae) from Southeast Asia. AB - A new genus of the spider subfamily Coelotinae, Sinocoelotes gen. n., with nine new species, is described from Yunnan and Sichuan Provinces in southern China. The new species are: Sinocoelotes cangshanensis sp. n. (?), Sinocoelotes hehuaensis sp. n. (??), Sinocoelotes luoshuiensis sp. n. (?), Sinocoelotes mangbangensis sp. n. (?) from Yunnan; Sinocoelotes kangdingensis sp. n. (?), Sinocoelotes ludingensis sp. n. (??), Sinocoelotes mahuanggouensis sp. n. (?), Sinocoelotes muliensis sp. n. (?), and Sinocoelotes yanyuanensis sp. n. (?) from Sichuan. In addition, six Coelotes species are transferred to the new genus: Sinocoelotes acicularis (Wang, Griswold & Ubick, 2009), comb. n. (??), Sinocoelotes forficatus (Liu & Li, 2010), comb. n. (??), Sinocoelotes guangxian (Zhang, Yang, Zhu & Song, 2003), comb. n. (??), Sinocoelotes pseudoterrestris (Schenkel, 1963), comb. n. (??), Sinocoelotes pseudoyunnanensis (Wang, Griswold & Ubick, 2009), comb. n. (??) and Sinocoelotes thailandensis (Dankittipakul & Wang, 2003), comb. n. (??). DNA barcodes of all the species were documented for future use. PMID- 27667933 TI - Sumakuru, a deeply-diverging new genus of lyssomanine jumping spiders from Ecuador (Araneae: Salticidae). AB - The lyssomanine jumping spider genus Sumakuru gen. n. is here described for Sumakuru bigal sp. n., from the Bigal River Biological Reserve in Ecuador. Known from a single male, the embolus of the palp takes the form of a smoothly arching curve, and appears fully mobile, being connected to the tegulum by a thin sclerite and a twisted hematodocha. Data from four gene regions (28S, 16SND1, CO1, wingless) indicate that Sumakuru is the sister group to all other sampled lyssomanines, diverging deeply on the stem lineage of the clade of other known lyssomanines. Unlike previous molecular results, the sampled species of Lyssomanes Hentz, 1845 are supported as monophyletic, with Chinoscopus Simon, 1900 as the sister to Lyssomanes. PMID- 27667934 TI - A new species of Falsopodabrus Pic characterized with geometric morphometrics (Coleoptera, Cantharidae). AB - A new species of Falsopodabrus Pic, 1927 is described, Falsopodabrus tridentatus Yang, sp. n. (Yunnan, China). Geometric morphometric analyses based on the shapes of pronotum and hind wing and comparisons with two sibling species, Falsopodabrus himalaicus Wittmer, 1974 and Falsopodabrus martensi (Wittmer, 1979), support the valid status of the new species, also confirmed by the characters of tarsal claws. In addition to Falsopodabrus himalaicus and Falsopodabrus martensi, Falsopodabrus kostali Svihla, 2004 and Falsopodabrus rolciki Svihla, 2004 are recorded from China for the first time. PMID- 27667935 TI - X-ray microscopy reveals endophallic structures in a new species of the ground beetle genus Trechus Clairville, 1806 from Baltic amber (Coleoptera, Carabidae, Trechini). AB - The third fossil species of the genus Trechus Clairville, 1806 is described from Baltic amber: Trechus exhibitorius sp. n. Details of external and internal morphology were analysed using X-ray micro-computed tomography (micro-CT) and important diagnostic features of the internal male genital sac (endophallus) are described in detail for the first time in a fossil ground beetle. Based on these data, we could assign Trechus exhibitorius sp. n. to Trechus sensu stricto and this new fossil species seems to represent a basal branch of a lineage comprising species diverse groups of extant Trechus mainly distributed in the Caucasus and Anatolia. Thus, our results support previous studies suggesting that Trechus is a phylogenetically old lineage already present in the Eocene with numerous species. PMID- 27667936 TI - A new species of Patania from the Hainan Island, China (Lepidoptera, Crambidae). AB - Patania clava sp. n. is described from the Diaoluo Mountain of Hainan Island, China. The new species is distinguished from its most similar congener, Patania iopasalis (Walker, 1859), by the following features: wingspan 33.0-35.0 mm (vs. 21.0-30.0 mm), ventral cilia of the male antenna as long as the diameter of flagellomere (vs. 1/4), the thick finger-like gnathos (vs. the short broad sheet like), a long thick needle-like cornutus stretching out from (vs. embedded in) a cluster of spicular cornuti near apex. Images of adult and genitalia of the new species are provided. PMID- 27667937 TI - Prognathodes basabei, a new species of butterflyfish (Perciformes, Chaetodontidae) from the Hawaiian Archipelago. AB - A new species of the butterflyfish genus Prognathodes is described from specimens collected at a depth of 55-61 m off Pearl and Hermes Atoll, Northwestern Hawaiian Islands. This species has been observed by mixed-gas divers and from submersibles at depths ranging from 45-187 m throughout the Hawaiian Archipelago, with shallower sightings in the Northwestern Hawaiian Islands and deeper in the Main Hawaiian Islands. It is similar to Prognathodes guezei (Mauge and Bauchot 1976) from the western Indian Ocean, and at least one other undescribed species of Prognathodes from Palau, differing from these species in the number of soft dorsal-fin rays, size of head, and body depth. There are also differences in the life color, and a substantial genetic difference from the Palauan species (d " .08 in mtDNA cytochrome oxidase I). PMID- 27667938 TI - Sphaerodoridae (Annelida) of the deep Northwestern Atlantic, including remarkable new species of Euritmia and Sphaerephesia. AB - Sphaerodoridae (Annelida) is a seeming uncommon and minimally diverse group of polychaetes in the northwestern Atlantic, with only seven species reported from the United States, and none from the eastern coast of Canada, before the present study. Review of the large Smithsonian collection (National Museum of Natural History, Washington) revealed the presence of two morphologically extraordinary undescribed species and added a new record to the north-western Atlantic region. Euritmia carolensis sp. n. is characterised by bearing approximately 20 sessile spherical papillae arranged in three transverse rows per segment, ventrum with 4 6 larger papillae near the parapodial bases and parapodia without papillae; bearing 4-5 simple chaetae that are enlarged subdistally. Sphaerephesia amphorata sp. n. is distinguished from other congeners in the presence of four longitudinal rows of sessile, bottle-shaped macrotubercles with exceptionally long digitiform terminal papilla, and parapodia with four rounded and small papillae, bearing 4-7 compound chaetae, with blades 7-11 times as long as wide. Other encountered species are also herein re-described, including intraspecific variation and updated iconography. Comparison of material also allowed some systematic changes in the group, including the synonymisation of the genus Amacrodorum with Euritmia, and the transfer of Ephesiopsis shivae to Ephesiella. A key to the species reported from the Northwestern Atlantic is provided. PMID- 27667939 TI - Borniopsis mortoni sp. n. (Heterodonta, Galeommatoidea, Galeommatidaesensu lato), a new bivalve commensal with a synaptid sea cucumber from Japan. AB - The Galeommatoidea is a bivalve superfamily that exhibits high species diversity in shallow waters. Many members of this superfamily are associated commensally with burrowing marine invertebrates in benthic sediments. The genus Borniopsis is known only from eastern Asia and exhibits high host diversity (e.g., mantis shrimps, crabs, holothurians, sipunculans and echiurans). A new species, Borniopsis mortoni sp. n., is described from mud flats at the mouth of the Souzu River, southwestern Shikoku Island, Japan. This species has elongate-ovate shells covered by a tan to dark brown periostracum, and lives attached by both its foot and byssal threads to the body surface of the synaptid sea cucumber Patinapta ooplax. Several individuals of Borniopsis mortoni are often found on the same host, but sometimes more than 10 individuals can occur together. Borniopsis mortoni is one of the smallest species in this genus. Probably, its small body size is an adaptation to the mode of life in a narrow host burrow. Until now, only two other Borniopsis species were known to have commensal associations with synaptids. Thus, this is the third example of a synaptid-associated species from this genus. In addition, we briefly review the galeommatoideans commensal with apodid sea cucumbers. PMID- 27667940 TI - The complete mitochondrial genome of the Chinese Daphnia pulex (Cladocera, Daphniidae). AB - Daphnia pulex has played an important role in fresh-water ecosystems. In this study, the complete mitochondrial genome of Daphnia pulex from Chaohu, China was sequenced for the first time. It was accomplished using long-PCR methods and a primer-walking sequencing strategy with genus-specific primers. The mitogenome was found to be 15,306 bp in length. It contained 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a typical control region. This research revealed an overall A+T content of 64.50%. All of the 22 typical animal tRNA genes had a classical clover-leaf structure except for trnS1, in which its DHU arm simply formed a loop. The lengths of small and large rRNA were 744 bp and 1,313 bp, respectively. The A+T-rich region was 723 bp in length, which is longer than that from the North American species (689 bp). In terms of structure and composition, many similarities were found between the Chinese and North American Daphnia pulex. PMID- 27667942 TI - Revision of the Palaearctic Gasteruption assectator aggregate, with special reference to Sweden (Hymenoptera, Gasteruptiidae). AB - The Palaearctic species of the Gasteruption assectator aggregate (Hymenoptera, Gasteruptiidae) are revised and three species are recognised. Two species are re instated: Gasteruption boreale (Thomson, 1883), stat. n. and Gasteruption nigritarse (Thomson, 1883), stat. n., and both are excluded from the synonymy with Gasteruption assectator (Linnaeus, 1758). The general distribution of both species is given for Europe and in detail for Sweden. A key to the valid Palaearctic species of the Gasteruption assectator aggregate is given; key characters and primary types are illustrated. Four new synonyms are listed: Foenus fumipennis Thomson, 1883, Trichofoenus breviterebrae Watanabe, 1934, and Gasteruption margotae Madl, 1987, are synonymized with Gasteruption boreale (Thomson, 1883) and Gasteruption brevicauda Kieffer, 1904, with Gasteruption undulatum (Abeille de Perrin, 1879). PMID- 27667941 TI - Yuebeipotamon calciatile, a new genus and new species of freshwater crab from southern China (Crustacea, Decapoda, Brachyura, Potamidae). AB - A new genus and species of freshwater crab, Yuebeipotamon calciatile gen. n., sp. n., is described from southern China. While the carapace features are superficially similar to species of Sinopotamon Bott, 1967, Longpotamon Shih, Huang & Ng, 2016, and Tenuilapotamon Dai, Song, Li, Chen, Wang & Hu, 1984, the new genus possesses a distinctive combination of carapace, ambulatory leg, male thoracic sternal, male abdominal, and gonopodal characters that distinguish it from these and other genera. Molecular evidence derived from the mitochondrial 16S rDNA supports the establishment of a new genus. PMID- 27667943 TI - Definition of the jianfengling species group of the ground beetle genus Orthogonius MacLeay (Coleoptera, Carabidae, Orthogoniini). AB - The jianfengling species group of the termitophilous carabid genus Orthogonius MacLeay, 1825 is defined and reviewed. This species group ranges from southern China, crossing Indochina and Myanmar to eastern India. To date, the jianfengling species group is composed of ten species, including six new species which are hereinafter described and illustrated: Orthogonius wrasei sp. n. (Myanmar), Orthogonius bellus sp. n. and Orthogonius limbourgi sp. n. (Vietnam), Orthogonius politior sp. n., Orthogonius aberlenci sp. n. (Laos) and Orthogonius meghalayaensis sp. n. (India). Habitus, elytral apices and male genitalia of all species are illustrated. A key to species and a distribution map of jianfengling species group are provided. PMID- 27667944 TI - Two new species of the genus Timia and a redescription of Timia mongolica (Diptera, Ulidiidae). AB - Two new species of the genus Timia Wiedemann, 1824 are described and illustrated. Timia lazebnayae sp. n. from Uzbekistan has yellow body and is similar to Timia gobica Zaitzev, 1982, differing from it only by the entirely yellow flagellomere 1. Timia shatalkini sp. n. from Mongolia has dark body and differs from all other dark-colored representatives of the genus by the cell r4+5 being completely closed, forming petiole at the wing apex. Timia mongolica Zaitsev, 1982 is redescribed and an updated key for yellow-coloured Timia is provided. PMID- 27667945 TI - Review of Pseudacrobasis Roesler, 1975 from China (Lepidoptera, Pyralidae, Phycitinae). AB - The genus Pseudacrobasis is reviewed for China. Pseudacrobasis dilatata sp. n. is described as new and compared with Psorosa tergestella (Ragonot, 1901). Images of adults and illustrations of genital structures are provided. PMID- 27667947 TI - Tardigrada of Ireland: a review of records and an updated checklist of species including a new addition to the Irish fauna. AB - The phylum Tardigrada was not recorded in Ireland until the Clare Island Survey of 1909-1911, with only rare subsequent reports on Irish tardigrade species. In recent decades, significant taxonomic revision has occurred within Tardigrada. This has resulted in the need for a review of all known historical records from Ireland and Northern Ireland in order to produce an updated checklist of valid taxa. The new checklist includes fifty-one tardigrade species and subspecies including a new addition to the Irish fauna reported herein, Echiniscus quadrispinosus quadrispinosus Richters, 1902 from Newtown, Ballyvaughan, Co. Clare. PMID- 27667946 TI - Type material of Platyhelminthes (Monogenoidea) housed in the Helminthological Collection of the Oswaldo Cruz Institute/ FIOCRUZ (CHIOC), Rio de Janeiro, Brazil, from 1979 to 2016. AB - A catalogue of type material of monogenoids deposited in the Helminthological Collection of the Oswaldo Cruz Institute, FIOCRUZ (CHIOC), between 1979 and 2016, is presented, given that the last list of types was produced in 1979. The monogenoid collection comprises type lots for 203 species, distributed across 14 families and 68 genera. Specific names are listed systematically, followed by type host, infection site, type locality, specimens with the collection numbers and references. The classification and the nomenclature of the species have been updated. PMID- 27667948 TI - A new species of Neoperla from China, with a redescription of the female of N. mnong Stark, 1987 (Plecoptera, Perlidae). AB - A new species of the Neoperla clymene group (Plecoptera, Perlidae), Neoperla chebalinga sp. n. from Guangdong Province of southern China is described, illustrated, and compared with related taxa. The new species is characterized by the slender aedeagal tube, strongly sclerotized dorsally, and weakly sclerotized ventrally with an upcurved, medial, finger-like membranous lobe. Additionally the aedeagal sac gradually tapers to a blunt apex with a dorsoapical patch of spines. A supplementary description of the female of Neoperla mnong Stark, 1987 from Guangdong Province, China is also given. PMID- 27667949 TI - A new genus and species of Rhizoecidae (Hemiptera, Sternorryncha, Coccomorpha) associated with Acropyga yaeyamensis (Hymenoptera, Formicidae, Formicinae). AB - Ishigakicoccus gen. n. shimadai sp. n. is described based on the adult female morphology. This new species was found in the nest of a rare Japanese ant, Acropyga yaeyamensis Terayama & Hashimoto, 1996, in Ishigaki Is., Japan. It resembles Capitisetella migrans (Green, 1933) and Pseudorhizoecus proximus Green, 1933. However, the new species differs from those two species in having small multilocular pores, large 3-5 locular pores on the medial area of ventral abdomen, and two different-sized body setae. This new species is also the first record of a potential trophobiont of Acropyga yaeyamensis. A key to Japanese species of Rhizoecidae is also provided. PMID- 27667950 TI - Taxonomy of Malagasy Nesomyrmex brevicornis species-group using conventional morphology-based approach. AB - Here we describe the diversity of the Malagasy Nesomyrmex brevicornis-group as the final installment of series describing the complete Malagasy Nesomyrmex fauna. In the current paper introduce the Nesomyrmex brevicornis-group, a newly outlined species group. We split this group from one of the four former groups, Nesomyrmex madecassus-group (sensu Csosz and Fisher 2015). The relatively small number of individuals available within the Nesomyrmex brevicornis-group relative to the large number of OTUs hampers the use of sophisticated statistical techniques to evaluate the morphological data. Instead, we assess the diversity of the Nesomyrmex brevicornis-group via a conventional morphology-based approach relying upon non-numeric characters (shape, sculpture, color etc.) recorded by simple eye inspection. Morphometric data are used as secondary data to confirm the most probable boundaries between species, but without employing statistical analyses. We rejected prior species hypotheses imposed by the primary approach if a non-overlapping range of a single index calculated from continuous numeric traits was found between two hypothesized species. Our methods render every species in this revisionary work separable via both salient features and morphometric traits. Our approach reveals the existence of nine morphologically distinct species, Nesomyrmex brevicornis sp. n., Nesomyrmex brunneus sp. n., Nesomyrmex cingulatus sp. n., Nesomyrmex edentates sp. n., Nesomyrmex flavigaster sp. n., Nesomyrmex longiceps sp. n., Nesomyrmex minutus sp. n., Nesomyrmex punctaticeps sp. n., and Nesomyrmex sellaris sp. n.. Geographic maps showing the distribution of each species are provided, along with an updated key to workers of Malagasy Nesomyrmex species groups that includes the newly outlined Nesomyrmex brevicornis-group. PMID- 27667951 TI - A new species of Strongylacron (Copepoda, Harpacticoida, Cletodidae) from intertidal mudflats in the Korean peninsula. AB - A new species, Strongylacron glabrum sp. n. is described from intertidal mudflats in the Korean peninsula. The new species is assigned to the monospecific genus Strongylacron Gee & Huys, 1996 in accordance with the generic morphological features of the rostrum, antennary exopod, and thoracic legs. However, Strongylacron glabrum sp. n. is clearly distinguished from the type species, Strongylacron buchholtzi (Boeck, 1873), by the naked anterior margin of rostrum, the elongate exopod and endopodal lobe of female P5 approximately 3.5 and 2.7 times as long as width, respectively, and the presence of 8-10 rod-like projections on prosomites. The genus Strongylacron is first recorded from Korean waters by the present study. PMID- 27667952 TI - A new species of the genus Petrolisthes Stimpson (Crustacea, Decapoda, Porcellanidae) from the Central Pacific, with remarks and new records for P. aegyptiacus Werding & Hiller. AB - Petrolisthes paulayi sp. n. is described from specimens collected in French Polynesia. The new species belongs to an assemblage of morphologically similar Indo-West Pacific (IWP) species, here designated as the "mesobranchial-spine group". All species in the group bear carapace spines, including one or more mesobranchial spines, and transverse, piliferous striations on the dorsal surface of carapace and chelipeds. Petrolisthes paulayi sp. n. is distinguishable from all species in the group by its forwardly produced, trilobate front, and a characteristic combination of carapace spines. We also report on the range extension and live coloration of Petrolisthes aegyptiacus Werding & Hiller, another species of the mesobranchial-spine group, so far considered a Red Sea endemic. Specimens from the Mascarene Islands confirm that the geographic range of the species extends to the southern Indian Ocean. While specimens morphologically similar to Petrolisthes aegyptiacus, and collected in the Line and Society Islands, suggest a large range extension to the Central Pacific, it is probable that these individuals represent an undescribed species closely related to Petrolisthes aegyptiacus. PMID- 27667953 TI - Revision of the genus Gryposmylus Kruger, 1913 (Neuroptera, Osmylidae) with a remarkable example of convergence in wing disruptive patterning. AB - The charismatic lance lacewing genus Gryposmylus Kruger, 1913 (Osmylidae: Protosmylinae) from South East Asia is revised with a new species (Gryposmylus pennyi sp. n.) described from Malaysia. The genus is diagnosed and both species in the genus redescribed and figured. An extraordinary example of morphological convergence is presented, with disruptive camouflaging wing markings in Gryposmylus pennyi sp. n. being remarkably similar to the South American green lacewing Vieira leschenaulti Navas (Chrysopidae). PMID- 27667954 TI - Parvitermes (Isoptera, Termitidae, Nasutitermitinae) in Central America: Two new termite species and reassignment of Nasutitermes mexicanus. AB - The termite genus Parvitermes is now recognized on the Central American mainland to include Parvitermes mexicanus, new combination (previously in Nasutitermes) and two new species, Parvitermes mesoamericanus sp. n. and Parvitermes yucatanus sp. n., herein described from soldiers and workers. These three species, nine West Indian Parvitermes, and Antillitermes subtilis all share characteristic enteric valve spines that orientate against intestinal flow. All species are subterranean nesters and cellulose feeders. Evidence is mounting that generic level endemicity may be completely absent among the West Indian nasutitermitine fauna and that its origins stem from Central America. PMID- 27667955 TI - Taxonomic revision of the New World genus Callotillus Wolcott (Cleridae, Tillinae), with the description of the new genus Neocallotillus, and an illustrated key of identification to species. AB - The New World checkered beetle genus Callotillus Wolcott, 1911 is revised and the new genus Neocallotillus established. The subspecies Callotillus elegans vafer Wolcott is synonymized with the nominal subspecies, Callotillus elegans elegans (Erichson), which is transferred to, and designated as the type species of Neocallotillus gen. n. as Neocallotillus elegans (Erichson, 1847), comb. n. Two additional species are transferred from Callotillus to the new genus: Neocallotillus intricatus (Wolcott & Dybas, 1947), comb. n. and Neocallotillus crusoe (Wolcott, 1923), comb. n., the latter tentatively and based on Wolcott's original description. Callotillus is now composed of two species: Callotillus eburneocinctus Wolcott, 1911 and Callotillus bahamensis Vaurie, 1952. All abovementioned species except Neocallotillus crusoe are diagnosed and redescribed. In the absence of reference material of Neocallotillus crusoe, Wolcott's original description is transcribed. An illustrated key to species is provided. Characters of taxonomic relevance are illustrated and discussed. Updated distribution maps and locality data for all specimens examined are presented. PMID- 27667956 TI - Five new species of Trigonopeltastes Burmeister and Schaum from Central America with new country records for other New World Trichiini (Coleoptera, Scarabaeidae, Cetoniinae). AB - Five new species of Trigonopeltastes Burmeister and Schaum, 1840 are described: Trigonopeltastes arborfloricola sp. n. from Nicaragua, Trigonopeltastes formidulosus sp. n. from Costa Rica, Trigonopeltastes henryi sp. n. from Costa Rica, Trigonopeltastes mombachoensis sp. n. from Nicaragua, and Trigonopeltastes warneri sp. n. from Belize and Guatemala. An updated key to species of Trigonopeltastes is presented. Trigonopeltastes nigrinus Bates, 1889 and Trigonopeltastes carus Bates, 1889 are placed in synonymy with Trigonopeltastes geometricus Schaum, 1841, syn. n.. The males of Trigonopeltastes aurovelutinus Curoe, 2011 and Trigonopeltastes simplex Bates, 1889 are described for the first time. New country records are given for the following: Giesbertiolus ornatus Howden, 1988: Costa Rica; Paragnorimus sambucus Howden, 1970: Guatemala; Trichiotinus bibens (Fabricius, 1775): Canada; Trigonopeltastes archimedes Schaum, 1841: Guatemala and Costa Rica; Trigonopeltastes frontalis Bates, 1889: Belize, Guatemala, and Honduras; Trigonopeltastes glabellus Howden, 1988: Guatemala; Trigonopeltastes geometricus Schaum, 1841: Honduras; Trigonopeltastes sallaei sallaei Bates, 1889: Guatemala and Honduras; Trigonopeltastes simplex Bates, 1889: Mexico; Trigonopeltastes variabilis Howden, 1968: Honduras. PMID- 27667957 TI - Rediscovery and identity of Pumilomyia protrahenda De Stefani (Diptera, Cecidomyiidae) in Sicily with redescription and reassessment of its taxonomic position. AB - A population of the gall midge Pumilomyia protrahenda De Stefani, 1919 causing galls on Artemisia arborescens (Asteraceae) was discovered near Palermo (Sicily) in 2008. This species had not been found since 1918. Detailed study of morphological characters of adults, larvae and pupae revealed that Pumilomyia protrahenda belongs to the genus Rhopalomyia Rubsaamen, 1892, tribe Rhopalomyiini. The monotypic genus Pumilomyia De Stefani, 1919 is therefore synonymized under Rhopalomyia Rubsaamen, 1892. Rhopalomyia protrahenda comb. n. is redescribed, with important morphological characters illustrated. Adults have one-segmented palpi, antennae with 12-13 short flagellomeres and long legs with simple tarsal claws. A neotype is designated in the present paper because the type of this species is lost. The host plant has a circum-Mediterranean distribution but the gall midge is currently known only from Sicily, where it completes several generations between January and May. PMID- 27667958 TI - How reliably can northeast Atlantic sand lances of the genera Ammodytes and Hyperoplus be distinguished? A comparative application of morphological and molecular methods. AB - Accurate stock assessments for each of the dominant species of sand lances in the northeast Atlantic Ocean and adjacent areas are not available due to the lack of a reliable identification procedure; therefore, appropriate measures of fisheries management or conservation of sand lances cannot be implemented. In this study, detailed morphological and molecular features are assessed to discriminate between four species of sand lances belonging to the genera Ammodytes and Hyperoplus. Morphological characters described by earlier authors as useful for identification of the genera are confirmed, and two additional distinguishing characters are added. A combination of the following morphological characters is recommended to distinguish between the genera Hyperoplus and Ammodytes: the protrusibility of the premaxillae, the presence of hooked ends of the prevomer, the number of dermal plicae, and the pectoral-fin length as a percentage of the standard length. The discriminant function analysis revealed that morphometric data are not very useful to distinguish the species of each of the two genera. The following meristic characters improve the separation of Hyperoplus lanceolatus from Hyperoplus immaculatus: the number of lower arch gill rakers, total number of gill rakers, numbers of caudal vertebrae and total vertebrae, and numbers of dorsal-fin and anal-fin rays. It is confirmed that Ammodytes tobianus differs from Ammodytes marinus by its belly scales that are organised in tight chevrons, scales which are present over the musculature at the base of the caudal fin, as well as by the lower numbers of dermal plicae, dorsal-fin rays, and total vertebrae. In contrast to the morphological data, mitochondrial COI sequences (DNA barcodes) failed to separate unambiguously the four investigated species. Ammodytes tobianus and Hyperoplus lanceolatus showed an overlap between intraspecific and interspecific K2P genetic distances and cannot be reliably distinguished using the common DNA barcoding approach. Ammodytes marinus and Hyperoplus immaculatus exhibited gaps between intraspecific and interspecific K2P distances of 2.73 and 3.34% respectively, indicating that their DNA barcodes can be used for species identification. As an alternative, short nuclear Rhodopsin sequences were analysed and one diagnostic character was found for each of the species Ammodytes marinus, Hyperoplus lanceolatus, and Hyperoplus immaculatus. Ammodytes tobianus can be characterised by the lack of species-specific mutations when compared to the other three species. In contrast to COI, the short nuclear sequences represent a useful alternative for rapid species identification whenever an examination of morphological characters is not available. PMID- 27667959 TI - A bias in the "mass-normalized" DTT response - an effect of non-linear concentration-response curves for copper and manganese. AB - The dithiothreitol (DTT) assay is widely used to measure the oxidative potential of particulate matter. Results are typically presented in mass-normalized units (e.g., pmols DTT lost per minute per microgram PM) to allow for comparison among samples. Use of this unit assumes that the mass-normalized DTT response is constant and independent of the mass concentration of PM added to the DTT assay. However, based on previous work that identified non-linear DTT responses for copper and manganese, this basic assumption (that the mass-normalized DTT response is independent of the concentration of PM added to the assay) should not be true for samples where Cu and Mn contribute significantly to the DTT signal. To test this we measured the DTT response at multiple PM concentrations for eight ambient particulate samples collected at two locations in California. The results confirm that for samples with significant contributions from Cu and Mn, the mass normalized DTT response can strongly depend on the concentration of PM added to the assay, varying by up to an order of magnitude for PM concentrations between 2 and 34 MUg mL-1. This mass dependence confounds useful interpretation of DTT assay data in samples with significant contributions from Cu and Mn, requiring additional quality control steps to check for this bias. To minimize this problem, we discuss two methods to correct the mass-normalized DTT result and we apply those methods to our samples. We find that it is possible to correct the mass-normalized DTT result, although the correction methods have some drawbacks and add uncertainty to DTT analyses. More broadly, other DTT-active species might also have non-linear concentration-responses in the assay and cause a bias. In addition, the same problem of Cu- and Mn-mediated bias in mass-normalized DTT results might affect other measures of acellular redox activity in PM and needs to be addressed. PMID- 27667960 TI - Insight solutions are correct more often than analytic solutions. AB - How accurate are insights compared to analytical solutions? In four experiments, we investigated how participants' solving strategies influenced their solution accuracies across different types of problems, including one that was linguistic, one that was visual and two that were mixed visual-linguistic. In each experiment, participants' self-judged insight solutions were, on average, more accurate than their analytic ones. We hypothesised that insight solutions have superior accuracy because they emerge into consciousness in an all-or-nothing fashion when the unconscious solving process is complete, whereas analytic solutions can be guesses based on conscious, prematurely terminated, processing. This hypothesis is supported by the finding that participants' analytic solutions included relatively more incorrect responses (i.e., errors of commission) than timeouts (i.e., errors of omission) compared to their insight responses. PMID- 27667961 TI - Modelling highly variable environmental factors to assess potential microbial respiration in complex floodplain landscapes. AB - The hydrological exchange conditions strongly determine the biogeochemical dynamics in river systems. More specifically, the connectivity of surface waters between main channels and floodplains is directly controlling the delivery of organic matter and nutrients into the floodplains, where biogeochemical processes recycle them with high rates of activity. Hence, an in-depth understanding of the connectivity patterns between main channel and floodplains is important for the modelling of potential gas emissions in floodplain landscapes. A modelling framework that combines steady-state hydrodynamic simulations with long-term discharge hydrographs was developed to calculate water depths as well as statistical probabilities and event durations for every node of a computation mesh being connected to the main river. The modelling framework was applied to two study sites in the floodplains of the Austrian Danube River, East of Vienna. Validation of modelled flood events showed good agreement with gauge readings. Together with measured sediment properties, results of the validated connectivity model were used as basis for a predictive model yielding patterns of potential microbial respiration based on the best fit between characteristics of a number of sampling sites and the corresponding modelled parameters. Hot spots of potential microbial respiration were found in areas of lower connectivity if connected during higher discharges and areas of high water depths. PMID- 27667962 TI - Impact of urban planning on household's residential decisions: An agent-based simulation model for Vienna. AB - Interest in assessing the sustainability of socio-ecological systems of urban areas has increased notably, with additional attention generated due to the fact that half the world's population now lives in cities. Urban areas face both a changing urban population size and increasing sustainability issues in terms of providing good socioeconomic and environmental living conditions. Urban planning has to deal with both challenges. Households play a major role by being affected by urban planning decisions on the one hand and by being responsible - among many other factors - for the environmental performance of a city (e.g. energy use). We here present an agent-based decision model referring to the city of Vienna, the capital of Austria, with a population of about 1.7 million (2.3 million within the metropolitan area, the latter being more than 25% of Austria's total population). Since the early 1990s, after decades of negative population growth, Vienna has been experiencing a steady increase in population, mainly driven by immigration. The aim of the agent-based decision model is to simulate new residential patterns of different household types based on demographic development and migration scenarios. Model results were used to assess spatial patterns of energy use caused by different household types in the four scenarios (1) conventional urban planning, (2) sustainable urban planning, (3) expensive centre and (4) no green area preference. Outcomes show that changes in preferences of households relating to the presence of nearby green areas have the most important impact on the distribution of households across the small-scaled city area. Additionally, the results demonstrate the importance of the distribution of different household types regarding spatial patterns of energy use. PMID- 27667963 TI - Automatic generation of water distribution systems based on GIS data. AB - In the field of water distribution system (WDS) analysis, case study research is needed for testing or benchmarking optimisation strategies and newly developed software. However, data availability for the investigation of real cases is limited due to time and cost needed for data collection and model setup. We present a new algorithm that addresses this problem by generating WDSs from GIS using population density, housing density and elevation as input data. We show that the resulting WDSs are comparable to actual systems in terms of network properties and hydraulic performance. For example, comparing the pressure heads for an actual and a generated WDS results in pressure head differences of +/-4 m or less for 75% of the supply area. Although elements like valves and pumps are not included, the new methodology can provide water distribution systems of varying levels of complexity (e.g., network layouts, connectivity, etc.) to allow testing design/optimisation algorithms on a large number of networks. The new approach can be used to estimate the construction costs of planned WDSs aimed at addressing population growth or at comparisons of different expansion strategies in growth corridors. PMID- 27667964 TI - Gated Trapped Ion Mobility Spectrometry Coupled to Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. AB - Analysis of molecules by ion mobility spectrometry coupled with mass spectrometry (IMS-MS) provides chemical information on the three dimensional structure and mass of the molecules. The coupling of ion mobility to trapping mass spectrometers has historically been challenging due to the large differences in analysis time between the two devices. In this paper we present a modification of the trapped ion mobility (TIMS) analysis scheme termed "Gated TIMS" that allows efficient coupling to a Fourier Transform Ion Cyclotron Resonance (FT-ICR) analyzer. Analyses of standard compounds and the influence of source conditions on the TIMS distributions produced by ion mobility spectra of labile ubiquitin protein ions are presented. Ion mobility resolving powers up to 100 are observed. Measured collisional cross sections of ubiquitin ions are in excellent qualitative and quantitative agreement to previous measurements. Gated TIMS FT ICR produces results comparable to those acquired using TIMS/time-of-flight MS instrument platforms as well as numerous drift tube IMS-MS studies published in the literature. PMID- 27667965 TI - Ionic liquids in chromatographic and electrophoretic techniques: toward additional improvements in the separation of natural compounds. AB - Due to their unique properties, in recent years, ionic liquids (ILs) have been largely investigated in the field of analytical chemistry. Particularly during the last sixteen years, they have been successfully applied in the chromatographic and electrophoretic analysis of value-added compounds extracted from biomass. Considering the growing interest in the use of ILs in this field, this critical review provides a comprehensive overview on the improvements achieved using ILs as constituents of mobile or stationary phases in analytical techniques, namely in capillary electrophoresis and its different modes, in high performance liquid chromatography, and in gas chromatography, for the separation and analysis of natural compounds. The impact of the IL chemical structure and the influence of secondary parameters, such as the IL concentration, temperature, pH, voltage and analysis time (when applied), are also critically addressed regarding the achieved separation improvements. Major conclusions on the role of ILs in the separation mechanisms and the performance of these techniques in terms of efficiency, resolution and selectivity are provided. Based on a critical analysis of all published results, some target-oriented ILs are suggested. Finally, current drawbacks and future challenges in the field are highlighted. In particular, the design and use of more benign and effective ILs as well as the development of integrated (and thus more sustainable) extraction-separation processes using IL aqueous solutions are suggested within a green chemistry perspective. PMID- 27667966 TI - Enhanced tunability afforded by aqueous biphasic systems formed by fluorinated ionic liquids and carbohydrates. AB - This work unveils the formation of novel aqueous biphasic systems (ABS) formed by perfluoroalkylsulfonate-based ionic liquids (ILs) and a large number of carbohydrates (monosaccharides, disaccharides and polyols) aiming at establishing more benign alternatives to the salts commonly used. The respective ternary phase diagrams were determined at 298 K. The aptitude of the carbohydrates to induce phase separation closely follows their hydration capability, while the length of the IL cation/anion fluorinated chain also plays a crucial role. Finally, these systems were investigated as liquid-liquid extraction strategies for four food dyes. Single-step extraction efficiencies for the carbohydrate-rich phase up to 94% were obtained. Remarkably and contrarily to the most investigated IL-salt ABS, most dyes preferentially migrate for the most hydrophilic and biocompatible carbohydrate-rich phase - an outstanding advantage when envisaging the products recovery and further use. On the other hand, more hydrophobic dyes preferentially partition to the IL-rich phase, disclosing therefore these novel systems as highly amenable to be tuned by the proper choice of the phase-forming components. PMID- 27667967 TI - Do abundance distributions and species aggregation correctly predict macroecological biodiversity patterns in tropical forests? AB - AIM: It has been recently suggested that different 'unified theories of biodiversity and biogeography' can be characterized by three common 'minimal sufficient rules': (1) species abundance distributions follow a hollow curve, (2) species show intraspecific aggregation, and (3) species are independently placed with respect to other species. Here, we translate these qualitative rules into a quantitative framework and assess if these minimal rules are indeed sufficient to predict multiple macroecological biodiversity patterns simultaneously. LOCATION: Tropical forest plots in Barro Colorado Island (BCI), Panama, and in Sinharaja, Sri Lanka. METHODS: We assess the predictive power of the three rules using dynamic and spatial simulation models in combination with census data from the two forest plots. We use two different versions of the model: (1) a neutral model and (2) an extended model that allowed for species differences in dispersal distances. In a first step we derive model parameterizations that correctly represent the three minimal rules (i.e. the model quantitatively matches the observed species abundance distribution and the distribution of intraspecific aggregation). In a second step we applied the parameterized models to predict four additional spatial biodiversity patterns. RESULTS: Species-specific dispersal was needed to quantitatively fulfil the three minimal rules. The model with species-specific dispersal correctly predicted the species-area relationship, but failed to predict the distance decay, the relationship between species abundances and aggregations, and the distribution of a spatial co occurrence index of all abundant species pairs. These results were consistent over the two forest plots. MAIN CONCLUSIONS: The three 'minimal sufficient' rules only provide an incomplete approximation of the stochastic spatial geometry of biodiversity in tropical forests. The assumption of independent interspecific placements is most likely violated in many forests due to shared or distinct habitat preferences. Furthermore, our results highlight missing knowledge about the relationship between species abundances and their aggregation. PMID- 27667968 TI - Preschool Teachers' Language and Literacy Practices with Dual Language Learners. AB - The purposes of this study were to (a) examine the degree to which teachers used linguistically responsive practices to support the language and literacy development of Spanish-speaking Dual Language Learners (DLL) and (b) to investigate the associations between these practices and select teacher-level factors. The sample consisted of 72 preschool teachers. Observational data were collected on practices. Teachers self-reported on language and culture beliefs, Spanish speaking ability, and classroom composition. Results indicated that teachers, including those who spoke Spanish, used few linguistically responsive practices to support preschool DLLs. Only Spanish-speaking ability was related to practices. Implications for targeted professional development are discussed. PMID- 27667969 TI - The Role of Negative Affect and Physiological Regulation in maternal attribution. AB - OBJECTIVE: Mothers who attribute child misbehaviors to children's intentions, and not to situational causes, show more hostile parenting behaviors. Why are some mothers more likely than others to make more hostile attributions (i.e., high intentional attributions and low situational attributions) when confronted with child challenging behaviors? We examined the relation between mothers' perception of child challenging behaviors and their hostile attributions of child misbehaviors, with an emphasis on how maternal negative affect and resting vagal activity moderated this relation. DESIGN: 160 mothers of 3- to 7-year-old children reported their perceptions of child problem behaviors, their attributions regarding child misbehaviors, and their temperamental negative affect. Mothers' respiratory sinus arrhythmia (RSA) was measured during resting state. RESULTS: Maternal perceptions of child challenging behaviors were positively related to hostile maternal attributions, and this relation was strongest in mothers with high negative affect and low resting RSA. CONCLUSIONS: These findings indicate the importance of considering mothers' affective and physiological attributes when examining social-cognitive processes in parenting. PMID- 27667970 TI - Treatment choices and subsequent attendance by substance-dependent patients who disengage from intensive outpatient treatment. AB - In an effort to increase engagement in effective treatment, we offered a choice of alternate evidence-based treatments to 137 alcohol- or cocaine-dependent adults (110 males, 27 females) who entered an intensive outpatient program (IOP) but disengaged within the first 8 weeks. We hypothesized that disengaged patients would choose and subsequently attend alternatives to IOP when given the chance, that their choices would be consistent with their previously-stated preferences, and that demographic and clinical characteristics would be predictive of alternatives chosen. Of 96 participants reached by phone, 19% chose no treatment; 49% chose to return to IOP; 24% chose individual psychotherapy; 6% chose telephone counseling; 2% chose naltrexone with medication management. There were few relationships between participant characteristics and choices made upon disengagement. Participants who chose alternative treatments were equally likely to attend their chosen treatment as those who chose IOP. Limited interest in alternative treatments may reflect allegiance to IOP, which was initially chosen by all participants. Implications for implementation of patient-centered adaptive treatment are discussed. PMID- 27667971 TI - Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System. AB - The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development. PMID- 27667974 TI - Editorial: Enamel Research: Mechanisms and Characterization. PMID- 27667972 TI - Distinct Aging Effects on Functional Networks in Good and Poor Cognitive Performers. AB - Brain network hubs are susceptible to normal aging processes and disruptions of their functional connectivity are detrimental to decline in cognitive functions in older adults. However, it remains unclear how the functional connectivity of network hubs cope with cognitive heterogeneity in an aging population. This study utilized cognitive and resting-state functional magnetic resonance imaging data, cluster analysis, and graph network analysis to examine age-related alterations in the network hubs' functional connectivity of good and poor cognitive performers. Our results revealed that poor cognitive performers showed age dependent disruptions in the functional connectivity of the right insula and posterior cingulate cortex (PCC), while good cognitive performers showed age related disruptions in the functional connectivity of the left insula and PCC. Additionally, the left PCC had age-related declines in the functional connectivity with the left medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). Most interestingly, good cognitive performers showed age-related declines in the functional connectivity of the left insula and PCC with their right homotopic structures. These results may provide insights of neuronal correlates for understanding individual differences in aging. In particular, our study suggests prominent protection roles of the left insula and PCC and bilateral ACC in good performers. PMID- 27667973 TI - Cannabidiol, among Other Cannabinoid Drugs, Modulates Prepulse Inhibition of Startle in the SHR Animal Model: Implications for Schizophrenia Pharmacotherapy. AB - Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats) strain, and on the future prospects resulting from these findings. PMID- 27667976 TI - Microcystin-LR Induced Apoptosis in Rat Sertoli Cells via the Mitochondrial Caspase-Dependent Pathway: Role of Reactive Oxygen Species. AB - Microcystins (MCs), the secondary metabolites of blue-green algae, are ubiquitous and major cyanotoxin contaminants. Besides the hepatopancreas/liver, the reproductive system is regarded as the most important target organ for MCs. Although reactive oxygen species (ROS) have been implicated in MCs-induced reproductive toxicity, the role of MCs in this pathway remains unclear. In the present study, Sertoli cells were employed to investigate apoptotic death involved in male reproductive toxicity of microcystin-LR (MC-LR). After exposure to various concentrations of MC-LR for 24 h, the growth of Sertoli cells was concentration-dependently decreased with an IC50 of ~32 MUg/mL. Mitochondria mediated apoptotic changes were observed in Sertoli cells exposed to 8, 16, and 32 MUg/mL MC-LR including the increased expression of caspase pathway proteins, collapse of mitochondrial membrane potential (MMP), and generation of ROS. Pretreatment with a global caspase inhibitor was found to depress the activation of caspases, and eventually increased the survival rate of Sertoli cells, implying that the mitochondrial caspases pathway is involved in MC-LR-induced apoptosis. Furthermore, N-acetyl-l-cysteine attenuated the MC-LR-induced intracellular ROS generation, MMP collapse and cytochrome c release, resulting in the inhibition of apoptosis. Taken together, the observed results suggested that MC-LR induced apoptotic death of Sertoli cells by the activation of mitochondrial caspases cascade, while its effects on the ROS-mediated signaling pathway may contribute toward the initiation of mitochondrial dysfunction. PMID- 27667975 TI - Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms. AB - Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na(+)/K(+)-ATPase has multiple alpha isoforms (1-3). The expression of the alpha subunit of the Na(+)/K(+)-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na(+)/K(+)-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The alpha1 isoform of the Na(+)/K(+)-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The alpha2 isoform of the Na(+)/K(+)-ATPase regulates intracellular Ca(2+) signaling, contractility and pathological hypertrophy. The alpha3 isoform of the Na(+)/K(+)-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na(+)/K(+)-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1) the distribution and function of isoform specific Na(+)/K(+)-ATPase in the cardiomyocytes. (2) the role of cardiac Na(+)/K(+)-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na(+)/K(+)-ATPase isoform may offer a new target for the prevention of cardiac remodeling. PMID- 27667977 TI - German Anxiety Barometer-Clinical and Everyday-Life Anxieties in the General Population. AB - The objective of this study was to test a time-efficient screening instrument to assess clinically relevant and everyday-life (e.g., economic, political, personal) anxieties. Furthermore, factors influencing these anxieties, correlations between clinical and everyday anxieties and, for the first time, anxiety during different stages of life were assessed in a representative sample of the general population (N = 2229). Around 30% of the respondents manifested at least one disorder-specific key symptom within 1 year (women > men), 8% reported severe anxiety symptoms. Two thirds of respondents reported minor everyday anxieties and 5% were strongly impaired, whereby persons with severe clinical symptoms were more frequently affected. A variety of potential influencing factors could be identified. These include, in addition to socioeconomic status, gender, general health, risk-taking, and leisure behavior, also some up to now little investigated possible protective factors, such as everyday-life mental activity. The observed effects are rather small, which, however, given the heterogeneity of the general population seems plausible. Although the correlative design of the study does not allow direct causal conclusions, it can, however, serve as a starting point for experimental intervention studies in the future. Together with time series from repeated representative surveys, we expect these data to provide a better understanding of the processes that underlie everyday life and clinical anxieties. PMID- 27667978 TI - Distinguishing Dispositional and Cultivated Forms of Mindfulness: Item-Level Factor Analysis of Five-Facet Mindfulness Questionnaire and Construction of Short Inventory of Mindfulness Capability. AB - The widely used Five-Facet Mindfulness Questionnaire (FFMQ) mixes the dispositional and cultivated forms of mindfulness, thereby resulting in factor issues in previous studies. The present study distinguished the two forms of mindfulness and developed a Short Inventory of Mindfulness Capability at the item level of FFMQ. Three facets of mindfulness, namely, Describing, Acting with Awareness, and Non-judging of Experience, were assessed using community (n = 433) and student (n = 347) samples. Both meditators and non-meditators participated. Exploratory and confirmatory factor analysis (CFA) revealed a three-factor model of mindfulness with 12 items (four items per subscale). Psychometric evaluation demonstrated the solid factor structure of the measurement with high factor loadings, good internal consistency, and convergent validities. Longitudinal analysis indicated that the Acting with Awareness facet was a significant predictor of depression and anxiety symptoms 6 months later. Discussions focused on the roles of mindfulness capability on mental health as well as the relationship between them. A higher-order factor of mindfulness should be used to examine the efficacy of intervention or monitor the changes. Researchers who need to study the specific role or efficacy of each facet should calculate the scores of different facets. PMID- 27667979 TI - Bilingual and Monolingual Idiom Processing Is Cut from the Same Cloth: The Role of the L1 in Literal and Figurative Meaning Activation. AB - The present study examines non-native (L2) and native (L1) listeners' access to figurative idiomatic meaning and literal constituent meaning in two cross-modal priming experiments. Proficient German learners of English (L2) and native speakers of American English (L1) responded to English target words preceded by English idioms embedded in non-biasing prime sentences in a lexical decision task. English idioms differed in levels of translatability: Lexical level idioms had word-for-word translation equivalents in German, while post-lexical level idioms had matching idiomatic concepts in German but could not be translated word for word. Target words either related to the figurative meaning of the idiom or related to the literal meaning of the final constituent word of the idiom (e.g., to pull someone's leg, literal target: walk, figurative target: joke). Both L1 and L2 listeners showed facilitatory priming for literally- and figuratively related target words compared to unrelated control target words, with only marginal differences between the listener groups. No effect of translatability was found; that is, the existence of word-for-word translation equivalents in German neither facilitated nor hindered meaning activation for German L2 listeners. The results are interpreted in the context of L1 and L2 models of idiom processing as well as further relevant translation studies. PMID- 27667980 TI - Predicting Affective Information - An Evaluation of Repetition Suppression Effects. AB - Both theoretical proposals and empirical studies suggest that the brain interprets sensory input based on expectations to mitigate computational burden. However, as social beings, much of sensory input is affectively loaded - e.g., the smile of a partner, the critical voice of a boss, or the welcoming gesture of a friend. Given that affective information is highly complex and often ambiguous, building up expectations of upcoming affective sensory input may greatly contribute to its rapid and efficient processing. This review points to the role of affective information in the context of the 'predictive brain'. It particularly focuses on repetition suppression (RS) effects that have recently been linked to prediction processes. The findings are interpreted as evidence for more pronounced prediction processes with affective material. Importantly, it is argued that bottom-up attention inflates the neural RS effect, and because affective stimuli tend to attract more bottom-up attention, it thereby particularly overshadows the magnitude of RS effects for this information. Finally, anxiety disorders, such as social phobia, are briefly discussed as manifestations of modulations in affective prediction. PMID- 27667981 TI - Proteomics Analysis of Three Different Strains of Mycobacterium tuberculosis under In vitro Hypoxia and Evaluation of Hypoxia Associated Antigen's Specific Memory T Cells in Healthy Household Contacts. AB - In vitro mimicking conditions are thought to reflect the environment experienced by Mycobacterium tuberculosis inside the host granuloma. The majority of in vitro dormancy experimental models use laboratory-adapted strains H37Rv or Erdman instead of prevalent clinical strains involved during disease outbreaks. Thus, we included the most prevalent clinical strains (S7 and S10) of M. tuberculosis from south India in addition to H37Rv for our in vitro oxygen depletion (hypoxia) experimental model. Cytosolic proteins were prepared from hypoxic cultures, resolved by two-dimensional electrophoresis and protein spots were characterized by mass spectrometry. In total, 49 spots were characterized as over-expressed or newly emergent between the three strains. Two antigens (ESAT-6, Lpd) out of the 49 characterized spots were readily available in recombinant form in our lab. Hence, these two genes were overexpressed, purified and used for in vitro stimulation of whole blood collected from healthy household contacts (HHC) and active pulmonary tuberculosis patients (PTB). Multicolor flow cytometry analysis showed high levels of antigen specific CD4(+) central memory T cells in the circulation of HHC compared to PTB (p < 0.005 for ESAT-6 and p < 0.0005 for Lpd). This shows proteins that are predicted to be up regulated during in vitro hypoxia in most prevalent clinical strains would indicate possible potential immunogens. In vitro hypoxia experiments with most prevalent clinical strains would also elucidate the probable true representative antigens involved in adaptive mechanisms. PMID- 27667982 TI - The Arctic Soil Bacterial Communities in the Vicinity of a Little Auk Colony. AB - Due to deposition of birds' guano, eggshells or feathers, the vicinity of a large seabirds' breeding colony is expected to have a substantial impact on the soil's physicochemical features as well as on diversity of vegetation and the soil invertebrates. Consequently, due to changing physicochemical features the structure of bacterial communities might fluctuate in different soil environments. The aim of this study was to investigate the bacterial assemblages in the Arctic soil within the area of a birds' colony and in a control sample from a topographically similar location but situated away from the colony's impact area. A high number of OTUs found in both areas indicates a highly complex microbial populations structure. The most abundant phyla in both of the tested samples were: Proteobacteria, Acidobacteria, Actinobacteria, and Chloroflexi, with different proportions in the total share. Despite differences in the physicochemical soil characteristics, the soil microbial community structures at the phylum level were similar to some extent in the two samples. The only share that was significantly higher in the control area when compared to the sample obtained within the birds' colony, belonged to the Actinobacteria phylum. Moreover, when analyzing the class level for each phylum, several differences between the samples were observed. Furthermore, lower proportions of Proteobacteria and Acidobacteria were observed in the soil sample under the influence of the bird's colony, which most probably could be linked to higher nitrogen concentrations in that sample. PMID- 27667983 TI - Detection of Low Frequency Multi-Drug Resistance and Novel Putative Maribavir Resistance in Immunocompromised Pediatric Patients with Cytomegalovirus. AB - Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks. Changes in consensus sequence and resistance mutations were analyzed for three ORFs targeted by anti-HCMV drugs and the frequencies of drug resistance mutations monitored. Targeted-enriched sequencing of clinical material detected mutations occurring at frequencies of 2%. Seven patients showed no evidence of drug resistance mutations. Four patients developed drug resistance mutations a mean of 16 weeks after starting treatment. In two patients, multiple resistance mutations accumulated at frequencies of 20% or less, including putative maribavir and ganciclovir resistance mutations P522Q (UL54) and C480F (UL97). In one patient, resistance was detected 14 days earlier than by PCR. Phylogenetic analysis suggested recombination or superinfection in one patient. Deep sequencing of HCMV enriched from clinical samples excluded resistance in 7 of 11 subjects and identified resistance mutations earlier than conventional PCR based resistance testing in 2 patients. Detection of multiple low level resistance mutations was associated with poor outcome. PMID- 27667984 TI - Functional Metagenomics of Spacecraft Assembly Cleanrooms: Presence of Virulence Factors Associated with Human Pathogens. AB - Strict planetary protection practices are implemented during spacecraft assembly to prevent inadvertent transfer of earth microorganisms to other planetary bodies. Therefore, spacecraft are assembled in cleanrooms, which undergo strict cleaning and decontamination procedures to reduce total microbial bioburden. We wanted to evaluate if these practices selectively favor survival and growth of hardy microorganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during the assembly of three NASA spacecraft: The Lockheed Martin Aeronautics' Multiple Testing Facility during DAWN, the Kennedy Space Center's Payload Hazardous Servicing Facility (KSC-PHSF) during Phoenix, and the Jet Propulsion Laboratory's Spacecraft Assembly Facility during Mars Science Laboratory. Sample sets were collected from the KSC-PHSF cleanroom at three time points: before arrival of the Phoenix spacecraft, during the assembly and testing of the Phoenix spacecraft, and after removal of the spacecraft from the KSC-PHSF facility. All samples were subjected to metagenomic shotgun sequencing on an Illumina HiSeq 2500 platform. Strict decontamination procedures had a greater impact on microbial communities than sampling location Samples collected during spacecraft assembly were dominated by Acinetobacter spp. We found pathogens and potential virulence factors, which determine pathogenicity in all the samples tested during this study. Though the relative abundance of pathogens was lowest during the Phoenix assembly, potential virulence factors were higher during assembly compared to before and after assembly, indicating a survival advantage. Decreased phylogenetic and pathogenic diversity indicates that decontamination and preventative measures were effective against the majority of microorganisms and well implemented, however, pathogen abundance still increased over time. Four potential pathogens, Acinetobacter baumannii, Acinetobacter lwoffii, Escherichia coli and Legionella pneumophila, and their corresponding virulence factors were present in all cleanroom samples. This is the first functional metagenomics study describing presence of pathogens and their corresponding virulence factors in cleanroom environments. The results of this study should be considered for microbial monitoring of enclosed environments such as schools, homes, hospitals and more isolated habitation such the International Space Station and future manned missions to Mars. PMID- 27667985 TI - Nitrification Is a Primary Driver of Nitrous Oxide Production in Laboratory Microcosms from Different Land-Use Soils. AB - Most studies on soil N2O emissions have focused either on the quantifying of agricultural N2O fluxes or on the effect of environmental factors on N2O emissions. However, very limited information is available on how land-use will affect N2O production, and nitrifiers involved in N2O emissions in agricultural soil ecosystems. Therefore, this study aimed at evaluating the relative importance of nitrification and denitrification to N2O emissions from different land-use soils and identifying the potential underlying microbial mechanisms. A (15)N-tracing experiment was conducted under controlled laboratory conditions on four agricultural soils collected from different land-use. We measured N2O fluxes, nitrate ([Formula: see text]), and ammonium ([Formula: see text]) concentration and (15)N2O, (15)[Formula: see text], and (15)[Formula: see text] enrichment during the incubation. Quantitative PCR was used to quantify ammonia oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Our results showed that nitrification was the main contributor to N2O production in soils from sugarcane, dairy pasture and cereal cropping systems, while denitrification played a major role in N2O production in the vegetable soil under the experimental conditions. Nitrification contributed to 96.7% of the N2O emissions in sugarcane soil followed by 71.3% in the cereal cropping soil and 70.9% in the dairy pasture soil, while only around 20.0% of N2O was produced from nitrification in vegetable soil. The proportion of nitrified nitrogen as N2O (PN2O-value) varied across different soils, with the highest PN2O-value (0.260/00) found in the cereal cropping soil, which was around 10 times higher than that in other three systems. AOA were the abundant ammonia oxidizers, and were significantly correlated to N2O emitted from nitrification in the sugarcane soil, while AOB were significantly correlated with N2O emitted from nitrification in the cereal cropping soil. Our findings suggested that soil type and land-use might have strongly affected the relative contribution of nitrification and denitrification to N2O production from agricultural soils. PMID- 27667986 TI - Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests. AB - Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher(r) and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the "toxic potential" of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed. PMID- 27667988 TI - Variation in Fumonisin and Ochratoxin Production Associated with Differences in Biosynthetic Gene Content in Aspergillus niger and A. welwitschiae Isolates from Multiple Crop and Geographic Origins. AB - The fungi Aspergillus niger and A. welwitschiae are morphologically indistinguishable species used for industrial fermentation and for food and beverage production. The fungi also occur widely on food crops. Concerns about their safety have arisen with the discovery that some isolates of both species produce fumonisin (FB) and ochratoxin A (OTA) mycotoxins. Here, we examined FB and OTA production as well as the presence of genes responsible for synthesis of the mycotoxins in a collection of 92 A. niger/A. welwitschiae isolates from multiple crop and geographic origins. The results indicate that (i) isolates of both species differed in ability to produce the mycotoxins; (ii) FB-nonproducing isolates of A. niger had an intact fumonisin biosynthetic gene (fum) cluster; (iii) FB-nonproducing isolates of A. welwitschiae exhibited multiple patterns of fum gene deletion; and (iv) OTA-nonproducing isolates of both species lacked the ochratoxin A biosynthetic gene (ota) cluster. Analysis of genome sequence data revealed a single pattern of ota gene deletion in the two species. Phylogenetic analysis suggest that the simplest explanation for this is that ota cluster deletion occurred in a common ancestor of A. niger and A. welwitschiae, and subsequently both the intact and deleted cluster were retained as alternate alleles during divergence of the ancestor into descendent species. Finally, comparison of results from this and previous studies indicate that a majority of A. niger isolates and a minority of A. welwitschiae isolates can produce FBs, whereas, a minority of isolates of both species produce OTA. The comparison also suggested that the relative abundance of each species and frequency of FB/OTA producing isolates can vary with crop and/or geographic origin. PMID- 27667990 TI - Response to Commentary: Arnica montana Effects on Gene Expression in a Human Macrophage Cell Line. Evaluation by Quantitative Real-Time PCR. PMID- 27667989 TI - Diverse Bacteria with Lignin Degrading Potentials Isolated from Two Ranks of Coal. AB - Taking natural coal as a "seed bank" of bacterial strains able to degrade lignin that is with molecular structure similar to coal components, we isolated 393 and 483 bacterial strains from a meager lean coal sample from Hancheng coalbed and a brown coal sample from Bayannaoer coalbed, respectively, by using different media. Statistical analysis showed that isolates were significantly more site specific than medium-specific. Of the 876 strains belonging to 27 genera in Actinobacteria, Firmicutes, and Proteobacteria, 612 were positive for lignin degradation function, including 218 strains belonging to 35 species in Hancheng and 394 strains belonging to 19 species in Zhongqi. Among them, the dominant lignin-degrading strains were Thauera (Hancheng), Arthrobacter (Zhongqi) and Rhizobium (both). The genes encoding the laccases- or laccase-like multicopper oxidases, key enzymes in lignin production and degradation, were detected in three genera including Massila for the first time, which was in high expression by real time PCR (qRT-PCR) detection, confirming coal as a good seed bank. PMID- 27667992 TI - IMGT/StatClonotype for Pairwise Evaluation and Visualization of NGS IG and TR IMGT Clonotype (AA) Diversity or Expression from IMGT/HighV-QUEST. AB - There is a huge need for standardized analysis and statistical procedures in order to compare the complex immune repertoires of antigen receptors immunoglobulins (IG) and T cell receptors (TR) obtained by next generation sequencing (NGS). NGS technologies generate millions of nucleotide sequences and have led to the development of new tools. The IMGT/HighV-QUEST, available since 2010, is the first global web portal for the analysis of IG and TR high throughput sequences. IMGT/HighV-QUEST provides standardized outputs for the characterization of the "IMGT clonotype (AA)" (AA for amino acids) and their comparison in up to one million sequences. Standardized statistical procedures for "IMGT clonotype (AA)" diversity or expression comparisons have recently been described, however, no tool was yet available. IMGT/StatClonotype, a new IMGT((r)) tool, evaluates and visualizes statistical significance of pairwise comparisons of IMGT clonotype (AA) diversity or expression, per V (variable), D (diversity), and J (joining) gene of a given IG or TR group, from NGS IMGT/HighV QUEST statistical output. IMGT/StatClonotype tool is incorporated in the R package "IMGTStatClonotype," with a user-friendly interface. IMGT/StatClonotype is downloadable at IMGT((r)) for users to evaluate pairwise comparison of IG and TR NGS statistical output from IMGT/HighV-QUEST and to visualize, on their web browser, the statistical significance of IMGT clonotype (AA) diversity or expression, per gene, the comparative analysis of CDR-IMGT and the V-D-J associations, in immunoprofiles from normal or pathological immune responses. PMID- 27667991 TI - B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production. AB - A small subset of B cells, termed B-1 cells, with developmental origins, phenotypes, and functions that are distinct from those of conventional B cells exist in mice. It contributes the vast majority of spontaneously produced "natural" IgM. Natural IgM is constitutively produced, even in the absence of microbiota, and fulfills many distinct functions in tissue homeostasis and host defense. B-1 cells also respond with IgM production to innate signals and pathogen exposure, while maintaining steady-state levels natural IgM. Thus, within the B-1 cell pool, cells of distinct and heterogeneous functionality must exist to facilitate these different functions. This review considers three factors that may contribute to this heterogeneity: first, developmental differences regarding the origins of the precursors, second, tissue-specific signals that may differentially affect B-1 cells in the tissue compartments, and finally responsiveness to self-antigens as well as innate and antigen-specific signals. All three are likely to shape the repertoire and responsiveness of B-1 cells to homeostatic- and antigen-induced signals and thus contribute to the functional heterogeneity among these innate-like B cells. PMID- 27667994 TI - Sweet Pepper (Capsicum annuum L.) Canopy Photosynthesis Modeling Using 3D Plant Architecture and Light Ray-Tracing. AB - Canopy photosynthesis has typically been estimated using mathematical models that have the following assumptions: the light interception inside the canopy exponentially declines with the canopy depth, and the photosynthetic capacity is affected by light interception as a result of acclimation. However, in actual situations, light interception in the canopy is quite heterogenous depending on environmental factors such as the location, microclimate, leaf area index, and canopy architecture. It is important to apply these factors in an analysis. The objective of the current study is to estimate the canopy photosynthesis of paprika (Capsicum annuum L.) with an analysis of by simulating the intercepted irradiation of the canopy using a 3D ray-tracing and photosynthetic capacity in each layer. By inputting the structural data of an actual plant, the 3D architecture of paprika was reconstructed using graphic software (Houdini FX, FX, Canada). The light curves and A/C i curve of each layer were measured to parameterize the Farquhar, von Caemmerer, and Berry (FvCB) model. The difference in photosynthetic capacity within the canopy was observed. With the intercepted irradiation data and photosynthetic parameters of each layer, the values of an entire plant's photosynthesis rate were estimated by integrating the calculated photosynthesis rate at each layer. The estimated photosynthesis rate of an entire plant showed good agreement with the measured plant using a closed chamber for validation. From the results, this method was considered as a reliable tool to predict canopy photosynthesis using light interception, and can be extended to analyze the canopy photosynthesis in actual greenhouse conditions. PMID- 27667993 TI - Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells. AB - Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-kappaB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-kappaB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent resistant membranes extracted from H. pylori-infected cells than in those from uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID- 27667995 TI - miR-203 Expression in Exfoliated Cells of Tongue Coating Represents a Sensitive and Specific Biomarker of Gastroesophageal Reflux Disease. AB - Background and Aim. MicroRNAs (miRNAs) have been implicated in the pathophysiology of numerous human diseases including gastroesophageal reflux disease (GERD). The objective of this study was to investigate the miRNA expression of exfoliated cells of the tongue in patients with GERD versus healthy controls (Ctrls). Methods. Using quantitative reverse-transcription PCR (qRT PCR), expression levels of six candidate miRNAs (miR-143, miR-145, miR-192, miR 194, miR-203, and miR-205) were examined across a discovery cohort of patients with GERD (n = 24) versus Ctrls (n = 24). These findings were confirmed across a validation cohort (GERD, n = 142; Ctrls, n = 48). Differences in miRNA expression levels were evaluated using the Mann-Whitney U test while the specificity and sensitivity were obtained using receiver-operator characteristic (ROC) curves. Results. miR-203 was significantly downregulated in GERD patients as compared to Ctrls (P < 0.0001) with ROC curve of 0.94 (95% CI: 0.90-0.97). The sensitivity and the specificity of miR-203 were 91.7% and 87.3%, respectively, in the GERD and Ctrls. These results suggest that miR-203 may be a useful diagnostic marker for discriminating GERD from Ctrls. Conclusions. miR-203 testing may assist in the diagnosis of patients with symptoms suggestive of GERD. PMID- 27667987 TI - Discovery, Molecular Mechanisms, and Industrial Applications of Cold-Active Enzymes. AB - Cold-active enzymes constitute an attractive resource for biotechnological applications. Their high catalytic activity at temperatures below 25 degrees C makes them excellent biocatalysts that eliminate the need of heating processes hampering the quality, sustainability, and cost-effectiveness of industrial production. Here we provide a review of the isolation and characterization of novel cold-active enzymes from microorganisms inhabiting different environments, including a revision of the latest techniques that have been used for accomplishing these paramount tasks. We address the progress made in the overexpression and purification of cold-adapted enzymes, the evolutionary and molecular basis of their high activity at low temperatures and the experimental and computational techniques used for their identification, along with protein engineering endeavors based on these observations to improve some of the properties of cold-adapted enzymes to better suit specific applications. We finally focus on examples of the evaluation of their potential use as biocatalysts under conditions that reproduce the challenges imposed by the use of solvents and additives in industrial processes and of the successful use of cold adapted enzymes in biotechnological and industrial applications. PMID- 27667997 TI - Prediction and In Silico Identification of Novel B-Cells and T-Cells Epitopes in the S1-Spike Glycoprotein of M41 and CR88 (793/B) Infectious Bronchitis Virus Serotypes for Application in Peptide Vaccines. AB - Bioinformatic analysis was used to predict antigenic B-cell and T-cell epitopes within the S1 glycoprotein of M41 and CR88 IBV strains. A conserved linear B-cell epitope peptide, YTSNETTDVTS(175-185), was identified in M41 IBV strains while three such epitopes types namely, VSNASPNSGGVD(279-290), HPKCNFRPENI(328-338), and NETNNAGSVSDCTAGT(54-69), were predicted in CR88 IBV strains. Analysis of MHCI binding peptides in M41 IBV strains revealed the presence of 15 antigenic peptides out of which 12 were highly conserved in 96-100% of the total M41 strains analysed. Interestingly three of these peptides, GGPITYKVM(208), WFNSLSVSI(356), and YLADAGLAI(472), relatively had high antigenicity index (>1.0). On the other hand, 11 MHCI binding epitope peptides were identified in CR88 IBV strains. Of these, five peptides were found to be highly conserved with a range between 90% and 97%. However, WFNSLSVSL(358), SYNISAASV(88), and YNISAASVA(89) peptides comparably showed high antigenicity scores (>1.0). Combination of antigenic B-cells and T-cells peptides that are conserved across many strains as approach to evoke humoral and CTL immune response will potentially lead to a broad-based vaccine that could reduce the challenges in using live attenuated vaccine technology in the control of IBV infection in poultry. PMID- 27667998 TI - Bacterial Etiology and Antibiotic Resistance Profile of Community-Acquired Urinary Tract Infections in a Cameroonian City. AB - Introduction. Community-acquired urinary tract infections (CAUTIs) are usually treated empirically. Geographical variations in etiologic agents and their antibiotic sensitivity patterns are common. Knowledge of antibiotic resistance trends is important for improving evidence-based recommendations for empirical treatment of UTIs. Our aim was to determine the major bacterial etiologies of CAUTIs and their antibiotic resistance patterns in a cosmopolitan area of Cameroon for comparison with prescription practices of local physicians. Methods. We performed a cross-sectional descriptive study at two main hospitals in Yaounde, collecting a clean-catch mid-stream urine sample from 92 patients having a clinical diagnosis of UTI. The empirical antibiotherapy was noted, and identification of bacterial species was done on CLED agar; antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Results. A total of 55 patients had samples positive for a UTI. Ciprofloxacin and amoxicillin/clavulanic acid were the most empirically prescribed antibiotics (30.9% and 23.6%, resp.); bacterial isolates showed high prevalence of resistance to both compounds. Escherichia coli (50.9%) was the most common pathogen, followed by Klebsiella pneumoniae (16.4%). Prevalence of resistance for ciprofloxacin was higher compared to newer quinolones. Conclusions. E. coli and K. pneumoniae were the predominant bacterial etiologies; the prevalence of resistance to commonly prescribed antibiotics was high. PMID- 27667996 TI - Osteosarcopenic Obesity Syndrome: What Is It and How Can It Be Identified and Diagnosed? AB - Conditions related to body composition and aging, such as osteopenic obesity, sarcopenia/sarcopenic obesity, and the newly termed osteosarcopenic obesity (triad of bone muscle and adipose tissue impairment), are beginning to gain recognition. However there is still a lack of definitive diagnostic criteria for these conditions. Little is known about the long-term impact of these combined conditions of osteoporosis, sarcopenia, and obesity in older adults. Many may go undiagnosed and progress untreated. Therefore, the objective of this research is to create diagnostic criteria for osteosarcopenic obesity in older women. The proposed diagnostic criteria are based on two types of assessments: physical, via body composition measurements, and functional, via physical performance measures. Body composition measurements such as T-scores for bone mineral density, appendicular lean mass for sarcopenia, and percent body fat could all be obtained via dual energy X-ray absorptiometry. Physical performance tests: handgrip strength, one-leg stance, walking speed, and sit-to-stand could be assessed with minimal equipment. A score could then be obtained to measure functional decline in the older adult. For diagnosing osteosarcopenic obesity and other conditions related to bone loss and muscle loss combined with obesity, a combination of measures may more adequately improve the assessment process. PMID- 27668000 TI - Real-Time Analysis of Endogenous Wnt Signalling in 3D Mesenchymal Stromal Cells. AB - Wnt signalling has been implicated in the regulation of stem cell self-renewal and differentiation; however, the majority of in vitro studies are carried out using monolayer 2D culture techniques. Here, we used mesenchymal stromal cell (MSC) EGFP reporter lines responsive to Wnt pathway activation in a 3D spheroid culture system to mimic better the in vivo environment. Endogenous Wnt signalling was then investigated under basal conditions and when MSCs were induced to undergo osteogenic and adipogenic differentiation. Interestingly, endogenous Wnt signalling was only active during 3D differentiation whereas 2D cultures showed no EGFP expression throughout an extended differentiation time-course. Furthermore, exogenous Wnt signalling in 3D adipogenic conditions inhibited differentiation compared to unstimulated controls. In addition, suppressing Wnt signalling by Dkk-1 restored and facilitated adipogenic differentiation in MSC spheroids. Our findings indicate that endogenous Wnt signalling is active and can be tracked in 3D MSC cultures where it may act as a molecular switch in adipogenesis. The identification of the signalling pathways that regulate MSCs in a 3D in vivo-like environment will advance our understanding of the molecular mechanisms that control MSC fate. PMID- 27667999 TI - Cytokines TNF-alpha, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells. AB - During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-alpha, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs). hASCs were treated with TNF alpha, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL) for 72 h mimicking bone repair. TNF alpha reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold), as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair. PMID- 27668001 TI - Social organization influences the exchange and species richness of medicinal plants in Amazonian homegardens. AB - Medicinal plants provide indigenous and peasant communities worldwide with means to meet their healthcare needs. Homegardens often act as medicine cabinets, providing easily accessible medicinal plants for household needs. Social structure and social exchanges have been proposed as factors influencing the species diversity that people maintain in their homegardens. Here, we assess the association between the exchange of medicinal knowledge and plant material and medicinal plant richness in homegardens. Using Tsimane' Amazonian homegardens as a case study, we explore whether social organization shapes exchanges of medicinal plant knowledge and medicinal plant material. We also use network centrality measures to evaluate people's location and performance in medicinal plant knowledge and plant material exchange networks. Our results suggest that social organization, specifically kinship and gender relations, influences medicinal plant exchange patterns significantly. Homegardens total and medicinal plant species richness are related to gardeners' centrality in the networks, whereby people with greater centrality maintain greater plant richness. Thus, together with agroecological conditions, social relations among gardeners and the culturally specific social structure seem to be important determinants of plant richness in homegardens. Understanding which factors pattern general species diversity in tropical homegardens, and medicinal plant diversity in particular, can help policy makers, health providers, and local communities to understand better how to promote and preserve medicinal plants in situ. Biocultural approaches that are also gender sensitive offer a culturally appropriate means to reduce the global and local loss of both biological and cultural diversity. PMID- 27668002 TI - The Effects of Nutritional Juice Supplementation on the Extent of Climacteric Symptoms: An Observational Study. AB - Objective. This study aims to evaluate the effect of daily dietary nutritional supplement on somatic, psychological, and urogenital symptoms in postmenopausal women. Material and Methods. In this study 28 healthy, symptomatic, peri- and postmenopausal women of 47-67 years of age were allocated to use the nutritional supplement JuicePLUS+(r). Primary research parameters: Menopause Rating Scale (MRS) was used to assess menopausal symptoms at baseline and after 8 and 16 weeks of treatment. Secondary parameters: proliferation behaviour of vaginal smear was scored at baseline and after treatment. Results. Treatment with the supplement resulted in a reduction of somatic, psychological, and urogenital symptoms. The overall MRS score showed an average improvement of 44.01%. Most benefits were observed for the psychological symptoms irritability (60.55%) and physical and mental exhaustion (49.08%); modest effects were observed for hot flashes (44.86%) and sleeping problems (35.56%). There was a minor improvement in sexual problems; 6 women reported an increased libido. No statistically significant effect was found in vaginal dryness and proliferation behaviour of vaginal mucosa. No adverse effects were observed. Conclusion. Dietary nutritional supplement may constitute an effective alternative therapy to conventional alternative medicine for somatic, psychological, and sexual symptoms. PMID- 27668003 TI - From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science. AB - Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes. PMID- 27668004 TI - Naoxintong/PPARalpha Signaling Inhibits H9c2 Cell Apoptosis and Autophagy in Response to Oxidative Stress. AB - Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA) and is widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. The aim of this study is to investigate the protective mechanism of NXT on H9c2 cells (cardiogenic cell line) in response to H2O2. MTT, Western blot, and flow cytometry (FCM) methods were used to identify the protective effect of NXT extract on H2O2-induced H9c2 cells. Here we found that NXT extract significantly increased H9c2 cell viability and reduced H2O2 induced cell apoptosis and autophagy. More importantly, NXT inhibited H2O2 induced H9c2 cell apoptosis and autophagy by increasing PPARalpha protein levels. In contrast, silenced PPARalpha terminated NXT protective effect on H2O2-induced H9c2 cells. These findings suggest that NXT/PPARalpha signaling suppressed H2O2 induced H9c2 cell apoptosis and autophagy. PMID- 27668005 TI - Effect of Betula pendula Leaf Extract on alpha-Glucosidase and Glutathione Level in Glucose-Induced Oxidative Stress. AB - B. pendula leaf is a common ingredient in traditional herbal combinations for treatment of diabetes in southeastern Europe. Present study investigated B. pendula ethanolic and aqueous extract as inhibitors of carbohydrate hydrolyzing enzymes, as well as their ability to restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress. Phytochemical analysis revealed presence of rutin and other quercetin derivatives, as well as chlorogenic acid. In general, ethanolic extract was richer in phenolic substances than the aqueous extract. Furthermore, a comprehensive analysis of antioxidant activity of two extracts (determined by DPPH and ABTS radical scavenging activity, total antioxidant activity, and chelating activity as well as ferric reducing antioxidant power) has shown that ethanolic extract was better radical scavenger and metal ion reductant. In addition, ethanolic extract effectively increased cellular glutathione levels caused by hyperglycemia and inhibited alpha glucosidase with the activity comparable to that of acarbose. Therefore, in vitro research using B. pendula plant extracts has confirmed their antidiabetic properties. PMID- 27668006 TI - Sakuranetin Inhibits Inflammatory Enzyme, Cytokine, and Costimulatory Molecule Expression in Macrophages through Modulation of JNK, p38, and STAT1. AB - Sakuranetin is flavonoid phytoalexin that serves as a plant antibiotic and exists in Prunus and several other plant species. Recently, we identified the anti inflammatory effect of Prunus yedoensis and found that there were few studies on the potential anti-inflammatory activity of sakuranetin, one of the main constituents of Prunus yedoensis. Here, we isolated peritoneal macrophages from thioglycollate-injected mice and examined whether sakuranetin affected the response of the macrophages in response to lipopolysaccharide (LPS) plus interferon- (IFN-) gamma or LPS only. Sakuranetin suppressed the synthesis of iNOS and COX2 in LPS/IFN-gamma stimulated cells and the secretion of TNF-alpha, IL-6, and IL-12 in LPS stimulated cells. The surface expression of the costimulatory molecules, CD86 and CD40, was also decreased. Among the LPS-induced signaling molecules, STAT1, JNK, and p38 phosphorylation was attenuated. These findings are evidence that sakuranetin acts as anti-inflammatory flavonoid and further study is required to evaluate its in vivo efficacy. PMID- 27668007 TI - Cardiovascular responses to a laboratory stressor in women: Assessing the role of body awareness. AB - Body awareness (BA) is characterised by a general tendency towards awareness and recognition of normal, non-emotive bodily processes and physical sensations. BA considers one's sensitivity towards and belief in how well they can sense, predict, and describe their bodily functions and sensations. This study investigated the role of BA in haemodynamic and anxiety responses to a laboratory stressor. Women (n = 40) completed assessments of BA and state/trait anxiety. Women with low BA displayed higher blood pressure (BP) and heart rate (HR) reactivity in response to the stressor than women with high BA. Delayed HR recovery poststressor was observed in women with low BA. BA was a significant predictor of haemodynamic reactivity over and above trait anxiety. BA effects on state anxiety were not observed. Thus, greater BA is associated with less haemodynamic stress reactivity in women lending further support for the development of BA interventions aimed at stress reduction. PMID- 27668008 TI - "I Don't Know What Fun Is": Examining the Intersection of Social Capital, Social Networks, and Social Recovery. AB - PURPOSE: The purpose of this paper is to understand how people with problematic drug use access positive social capital. Social capital is defined as relations that provide valuable resources to individuals through participation in social networks. People with low socioeconomic status remain at a disadvantage for acquiring positive social capital, a component of recovery capital. The concept of social recovery emphasises the relational processes of recovery. DESIGN/METHODOLOGY/APPROACH: In-depth life history data were collected from 29 individuals who used heroin, cocaine, crack, or methamphetamine for at least five years, have less than a high school education, and unstable employment and housing. Qualitative data were coded for social networks accessed throughout the life course, distinguished by bonding, bridging and linking social capital. FINDINGS: Social networks included drug treatment programs; non-drug-using family and friends; religious/spiritual groups; workplace networks, and social clubs/activities. Bonding and/or bridging social capital were acquired through treatment, family and friends, religious/spiritual groups, workplaces, and social clubs. Linking social capital was not acquired through any social networks available, and many barriers to accessing mainstream social networks were found. LIMITATIONS: This is a small study conducted in the US. SOCIAL IMPLICATIONS: A greater focus on social recovery is needed to achieve sustained recovery for individuals lacking access to and engagement in mainstream social networks. PRACTICAL IMPLICATIONS: Social recovery is proposed as an analytical tool as well as for developing prevention, intervention, and treatment strategies. PMID- 27668010 TI - Using Eye Tracking to Understand Infants' Attentional Bias for Faces. AB - Infants have a natural tendency to look at adults' faces, possibly to help initiate vital interactions with caregivers during sensitive periods of development. Recent studies using eye-tracking technologies have identified the mechanisms that underlie infants' capacity to orient and hold attention on faces. These studies have shown that the bias for faces is weak in young infants, but becomes more robust and resistant to distraction during the second half of the 1st year. This development is apparently related to more general changes in infants' attention and control of eye movement. As a tractable and reproducible aspect of infant behavior, the attention bias for faces can be used to examine the neural correlates of attention and may be a way to monitor early neurodevelopment in infants. PMID- 27668009 TI - Stain-free histopathology by programmable supercontinuum pulses. AB - The preparation, staining, visualization, and interpretation of histological images of tissue is well-accepted as the gold standard process for the diagnosis of disease. These methods were developed historically, and are used ubiquitously in pathology, despite being highly time and labor intensive. Here we introduce a unique optical imaging platform and methodology for label-free multimodal multiphoton microscopy that uses a novel photonic crystal fiber source to generate tailored chemical contrast based on programmable supercontinuum pulses. We demonstrate collection of optical signatures of the tumor microenvironment, including evidence of mesoscopic biological organization, tumor cell migration, and (lymph-)angiogenesis collected directly from fresh ex vivo mammary tissue. Acquisition of these optical signatures and other cellular or extracellular features, which are largely absent from histologically processed and stained tissue, combined with an adaptable platform for optical alignment-free programmable-contrast imaging, offers the potential to translate stain-free molecular histopathology into routine clinical use. PMID- 27668012 TI - Refining The Grain: Using Resident-Based Walkability Audits To Better Understand Walkable Urban Form. AB - Researchers use measures of street connectivity to assess neighborhood walkability and many studies show a relationship between neighborhood design and walking activity. Yet, the core of those connectivity measures are based on constructs designed for analyzing automobile mobility - the street network - not pedestrian movement. This paper examines the effect of a finer grained characterization of street connectivity and illustrates the idea using parent ratings of street and intersection walkability for children throughout a suburban school district in Oregon. Several policy and practice recommendations are presented, including a discussion that extends Michael Southworth's (1993; 2005) foundational representation of streets and the walkable city using a refined, more pedestrian-centered approach to visualizing connectivity and walkable urban form. PMID- 27668011 TI - The effects of embodied rhythm and robotic interventions on the spontaneous and responsive verbal communication skills of children with Autism Spectrum Disorder (ASD): A further outcome of a pilot randomized controlled trial. AB - The current manuscript is the second in a mini-series of manuscripts reporting the effects of alternative, movement-based, rhythm and robotic interventions on the social communication skills of 36 school-age children with ASD. This pilot randomized controlled trial compared the effects of 8-weeks of rhythm and robotic interventions to those of a standard-of-care, comparison intervention. The first manuscript reported intervention effects on the spontaneous and responsive social attention skills of children. In this manuscript, we report intervention effects on the spontaneous and responsive verbal communication skills of children. Communication skills were assessed within a standardized test of responsive communication during the pretest and posttest as well as using training-specific measures of social verbalization during early, mid, and late training sessions. The rhythm and comparison groups improved on the standardized test in the posttest compared to the pretest. The rhythm and robot groups increased levels of social verbalization across training sessions. Movement-based and stationary contexts afforded different types and amounts of communication in children with ASD. Overall, movement-based interventions are a promising tool to enhance verbal and non-verbal communication skills in children with ASD. PMID- 27668013 TI - Genotypic diversity effects on biomass production in native perennial bioenergy cropping systems. AB - The perennial grass species that are being developed as biomass feedstock crops harbor extensive genotypic diversity, but the effects of this diversity on biomass production are not well understood. We investigated the effects of genotypic diversity in switchgrass (Panicum virgatum) and big bluestem (Andropogon gerardii) on perennial biomass cropping systems in two experiments conducted over 2008-2014 at a 5.4-ha fertile field site in northeastern Illinois, USA. We varied levels of switchgrass and big bluestem genotypic diversity using various local and nonlocal cultivars - under low or high species diversity, with or without nitrogen inputs - and quantified establishment, biomass yield, and biomass composition. In one experiment ('agronomic trial'), we compared three switchgrass cultivars in monoculture to a switchgrass cultivar mixture and three different species mixtures, with or without N fertilization. In another experiment ('diversity gradient'), we varied diversity levels in switchgrass and big bluestem (1, 2, 4, or 6 cultivars per plot), with one or two species per plot. In both experiments, cultivar mixtures produced yields equivalent to or greater than the best cultivars. In the agronomic trial, the three switchgrass mixture showed the highest production overall, though not significantly different than best cultivar monoculture. In the diversity gradient, genotypic mixtures had one-third higher biomass production than the average monoculture, and none of the monocultures were significantly higher yielding than the average mixture. Year-to year variation in yields was lowest in the three-cultivar switchgrass mixtures and Cave-In-Rock (the southern Illinois cultivar) and also reduced in the mixture of switchgrass and big bluestem relative to the species monocultures. The effects of genotypic diversity on biomass composition were modest relative to the differences among species and genotypes. Our findings suggest that local genotypes can be included in biomass cropping systems without compromising yields and that genotypic mixtures could help provide high, stable yields of high quality biomass feedstocks. PMID- 27668014 TI - Community-based adaptation research in the Canadian Arctic. AB - Community-based adaptation (CBA) has emerged over the last decade as an approach to empowering communities to plan for and cope with the impacts of climate change. While such approaches have been widely advocated, few have critically examined the tensions and challenges that CBA brings. Responding to this gap, this article critically examines the use of CBA approaches with Inuit communities in Canada. We suggest that CBA holds significant promise to make adaptation research more democratic and responsive to local needs, providing a basis for developing locally appropriate adaptations based on local/indigenous and Western knowledge. Yet, we argue that CBA is not a panacea, and its common portrayal as such obscures its limitations, nuances, and challenges. Indeed, if uncritically adopted, CBA can potentially lead to maladaptation, may be inappropriate in some instances, can legitimize outside intervention and control, and may further marginalize communities. We identify responsibilities for researchers engaging in CBA work to manage these challenges, emphasizing the centrality of how knowledge is generated, the need for project flexibility and openness to change, and the importance of ensuring partnerships between researchers and communities are transparent. Researchers also need to be realistic about what CBA can achieve, and should not assume that research has a positive role to play in community adaptation just because it utilizes participatory approaches. WIREs Clim Change 2016, 7:175-191. doi: 10.1002/wcc.376 For further resources related to this article, please visit the WIREs website. PMID- 27668015 TI - Accuracy of pharmaceutical company licensing predictions: projected versus actual licensing dates. AB - OBJECTIVES: To determine the accuracy of pharmaceutical companies' predictions of drug licensing timeframes for their products in late stage clinical development. METHODS: We compared predicted licensing dates provided to the National Institute for Health Research Horizon Scanning Research and Intelligence Centre by pharmaceutical companies against actual marketing authorisation application (MAA) and marketing authorisation (MA) dates published by the European Medicines Agency for drugs granted authorisation between 2009 and 2013. KEY FINDINGS: One hundred and twenty-three drugs met our inclusion criteria. About 78% were new drugs and 16% had orphan designation. Less than half (44%) and less than a quarter (24%) of MAA and MA predictions respectively were considered accurate (same month or 1 month either side of the actual date). Pharmaceutical companies were significantly more accurate in predicting MAA dates than MA dates (P < 0.001). For accurate predictions, the mean duration between the prediction being made and the actual MAA and MA dates were 17.5 and 18.7 months respectively. Out of the total 108 MA predictions, almost two-thirds (65.4%, 16/26) of short-term predictions (made in the 2 years prior to the actual MA) were accurate. For predicted dates that were earlier than the actual MA date, there was a positive relationship between accuracy and the time between the prediction and authorisation. CONCLUSIONS: Even in predicting near events from well-informed sources, accuracy is imperfect. There appears to be an optimum time for the provision of accurate information on predicted MAA and MA dates for drugs. This information is crucial for effective early awareness and alert activities. PMID- 27668016 TI - Combined nonlinear metrics to evaluate spontaneous EEG recordings from chronic spinal cord injury in a rat model: a pilot study. AB - Spinal cord injury (SCI) is a high-cost disability and may cause permanent loss of movement and sensation below the injury location. The chance of cure in human after SCI is extremely limited. Instead, neural regeneration could have been seen in animals after SCI, and such regeneration could be retarded by blocking neural plasticity pathways, showing the importance of neural plasticity in functional recovery. As an indicator of nonlinear dynamics in the brain, sample entropy was used here in combination with detrended fluctuation analysis (DFA) and Kolmogorov complexity to quantify functional plasticity changes in spontaneous EEG recordings of rats before and after SCI. The results showed that the sample entropy values were decreased at the first day following injury then gradually increased during recovery. DFA and Kolmogorov complexity results were in consistent with sample entropy, showing the complexity of the EEG time series was lost after injury and partially regained in 1 week. The tendency to regain complexity is in line with the observation of behavioral rehabilitation. A critical time point was found during the recovery process after SCI. Our preliminary results suggested that the combined use of these nonlinear dynamical metrics could provide a quantitative and predictive way to assess the change of neural plasticity in a spinal cord injury rat model. PMID- 27668017 TI - Operator functional state estimation based on EEG-data-driven fuzzy model. AB - This paper proposed a max-min-entropy-based fuzzy partition method for fuzzy model based estimation of human operator functional state (OFS). The optimal number of fuzzy partitions for each I/O variable of fuzzy model is determined by using the entropy criterion. The fuzzy models were constructed by using Wang Mendel method. The OFS estimation results showed the practical usefulness of the proposed fuzzy modeling approach. PMID- 27668019 TI - The influence of potassium concentration on epileptic seizures in a coupled neuronal model in the hippocampus. AB - Experiments on hippocampal slices have recorded that a novel pattern of epileptic seizures with alternating excitatory and inhibitory activities in the CA1 region can be induced by an elevated potassium ion (K(+)) concentration in the extracellular space between neurons and astrocytes (ECS-NA). To explore the intrinsic effects of the factors (such as glial K(+) uptake, Na(+)-K(+)-ATPase, the K(+) concentration of the bath solution, and K(+) lateral diffusion) influencing K(+) concentration in the ECS-NA on the epileptic seizures recorded in previous experiments, we present a coupled model composed of excitatory and inhibitory neurons and glia in the CA1 region. Bifurcation diagrams showing the glial K(+) uptake strength with either the Na(+)-K(+)-ATPase pump strength or the bath solution K(+) concentration are obtained for neural epileptic seizures. The K(+) lateral diffusion leads to epileptic seizure in neurons only when the synaptic conductance values of the excitatory and inhibitory neurons are within an appropriate range. Finally, we propose an energy factor to measure the metabolic demand during neuron firing, and the results show that different energy demands for the normal discharges and the pathological epileptic seizures of the coupled neurons. PMID- 27668018 TI - Noise effects on robust synchronization of a small pacemaker neuronal ensemble via nonlinear controller: electronic circuit design. AB - In this paper, we report on the synchronization of a pacemaker neuronal ensemble constituted of an AB neuron electrically coupled to two PD neurons. By the virtue of this electrical coupling, they can fire synchronous bursts of action potential. An external master neuron is used to induce to the whole system the desired dynamics, via a nonlinear controller. Such controller is obtained by a combination of sliding mode and feedback control. The proposed controller is able to offset uncertainties in the synchronized systems. We show how noise affects the synchronization of the pacemaker neuronal ensemble, and briefly discuss its potential benefits in our synchronization scheme. An extended Hindmarsh-Rose neuronal model is used to represent a single cell dynamic of the network. Numerical simulations and Pspice implementation of the synchronization scheme are presented. We found that, the proposed controller reduces the stochastic resonance of the network when its gain increases. PMID- 27668020 TI - Bursting dynamics remarkably improve the performance of neural networks on liquid computing. AB - Burst firings are functionally important behaviors displayed by neural circuits, which plays a primary role in reliable transmission of electrical signals for neuronal communication. However, with respect to the computational capability of neural networks, most of relevant studies are based on the spiking dynamics of individual neurons, while burst firing is seldom considered. In this paper, we carry out a comprehensive study to compare the performance of spiking and bursting dynamics on the capability of liquid computing, which is an effective approach for intelligent computation of neural networks. The results show that neural networks with bursting dynamic have much better computational performance than those with spiking dynamics, especially for complex computational tasks. Further analysis demonstrate that the fast firing pattern of bursting dynamics can obviously enhance the efficiency of synaptic integration from pre-neurons both temporally and spatially. This indicates that bursting dynamic can significantly enhance the complexity of network activity, implying its high efficiency in information processing. PMID- 27668021 TI - Event-based exponential synchronization of complex networks. AB - In this paper, we consider exponential synchronization of complex networks. The information diffusions between nodes are driven by properly defined events. By employing the M-matrix theory, algebraic graph theory and the Lyapunov method, two kinds of distributed event-triggering laws are designed, which avoid continuous communications between nodes. Then, several criteria that ensure the event-based exponential synchronization are presented, and the exponential convergence rates are obtained as well. Furthermore, we prove that Zeno behavior of the event-triggering laws can be excluded before synchronization being achieved, that is, the lower bounds of inter-event times are strictly positive. Finally, a simulation example is provided to illustrate the effectiveness of theoretical analysis. PMID- 27668022 TI - Stability and synchronization analysis of inertial memristive neural networks with time delays. AB - This paper is concerned with the problem of stability and pinning synchronization of a class of inertial memristive neural networks with time delay. In contrast to general inertial neural networks, inertial memristive neural networks is applied to exhibit the synchronization and stability behaviors due to the physical properties of memristors and the differential inclusion theory. By choosing an appropriate variable transmission, the original system can be transformed into first order differential equations. Then, several sufficient conditions for the stability of inertial memristive neural networks by using matrix measure and Halanay inequality are derived. These obtained criteria are capable of reducing computational burden in the theoretical part. In addition, the evaluation is done on pinning synchronization for an array of linearly coupled inertial memristive neural networks, to derive the condition using matrix measure strategy. Finally, the two numerical simulations are presented to show the effectiveness of acquired theoretical results. PMID- 27668024 TI - Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study. AB - BACKGROUND: Oral solution N-acetylcysteine (NAC) is an antidote for acetaminophen overdose, but its unpleasant taste and aroma can impede delivery even after the coadministration of antiemetic medications. Flavored effervescent NAC tablets dissolved in water might be a more palatable formulation than oral solution NAC diluted with soft drink. OBJECTIVES: To evaluate the relative bioavailability of these 2 formulations and assess subjective preferences between them. METHODS: Thirty healthy adult volunteers (mean [SD] = 35.2 [9.14] years) were enrolled in this open-label, randomized, single-dose, crossover study, with a 7-day washout period. Volunteers were randomized to receive 11 g effervescent test formulation or the reference product under fasting conditions, after which 19 serial blood samples were collected over 48 hours. Total plasma NAC concentrations were evaluated by LC-MS, and pharmacokinetic parameters were calculated. The 2 formulations were considered bioequivalent if the 90% CIs of log-transformed ratios of pharmacokinetic parameters were within the predetermined bioequivalence range (80%-125%) established by the US Food and Drug Administration. Within 15 minutes of dosing, subjects were also asked to rank formulation attributes on a 5 point hedonic scale, with mean group differences analyzed by Wilcoxon signed rank test. Safety-profile assessment included treatment-emergent adverse events, physical examination, chemistry, and hematology parameters. RESULTS: The concentration-versus-time profiles were similar for the 2 formulations, with mean Cmax of 26.5 MUg/mL for effervescent NAC tablets and 28.4 MUg/mL for oral solution NAC. The 90% CIs for the pharmacokinetic parameters met the criteria for concluding bioequivalence, and subjects preferred effervescent NAC tablets in terms of taste (P = 0.0247), flavor (P = 0.0082), texture (P = 0.009), and overall likeability (P = 0.0012), but there was no difference for smell (P = 0.0533). All treatment-emergent adverse events were mild, with no differences between the treatment groups. CONCLUSIONS: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669. (Curr Ther Res Clin Exp. 2016; 83C:1-7) (c) 2016 Elsevier HS Journals, Inc. PMID- 27668023 TI - Paroxysmal posterior variant alien hand syndrome associated with parietal lobe infarction: case presentation. AB - Alien hand syndrome (AHS) is an involuntary and rare neurological disorder emerges at upper extremity. AHS is a disconnection syndrome with the symptoms of losing sense of agency and sense of ownership, and presence of involuntary autonomic motor activity. There are frontal, callosal and posterior types of AHS and each of them occurs depend on the lesions of different of the brain. Posterior variant is a rarely encountered AHS type compared to others. AHS, generally regarded as persistent, but rarely maybe observed as paroxysmal. In this article, we present 71 year old patient with right posterior parietal lobe infarction and developed posterior variant AHS on left arm 1 month after discharge from the hospital. To discriminate AHS from conditions such as extrapyramidal movement disorders and epileptic seizures that take part in differential diagnosis should be kept in mind by the clinicians. Wrong and unnecessary treatments could be prevented in this way. PMID- 27668025 TI - A Novel Topical Combination Ointment with Antimicrobial Activity against Methicillin-Resistant Streptococcus aureus, Gram-Negative Superbugs, Yeasts, and Dermatophytic Fungi. AB - BACKGROUND: The use of topical antimicrobial agents for management of minor skin infections is a clinical strategy that is commonly practiced in the community. Coupled with the use of topical antimicrobial agents is the emergence of antibiotic-resistant strains of pathogens leading to the need for alternative treatments. OBJECTIVE: A novel topical combination ointment consisting of salicylic acid, oak bark extract, benzoic acid, and polyethylene glycol (Bensal HP, Sonar products Inc., Carlstadt, NJ) with antimicrobial properties was assessed to determine its spectrum of activity. METHODS: One hundred eighty-four bacterial and fungal isolates from culture collections that included multidrug resistant bacteria such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp, and gram-negative so-called superbugs, as well as yeasts and filamentous fungi, were investigated by cylinder diffusion and agar dilution assays. RESULTS: All 184 bacterial and fungal isolates were susceptible to the combination ointment at the clinically applied concentration and there was no evidence of cross-resistance between Bensal HP and other classes of antimicrobials. In time-kill tests, Bensal HP was rapidly bactericidal against P aeruginosa ATCC 27853 and methicillin-resistant S aureus SA179 at 4 * the MIC, a concentration that is applied clinically. CONCLUSIONS: The results of this study suggest that this combination ointment has a broad in vitro spectrum of antimicrobial activity against both more common bacterial and fungal pathogens and may be particularly useful for treatment of infections by multidrug-resistant organisms. Additional studies are warranted to investigate the full clinical utility as a therapeutic agent and also for possible infection control interventions. PMID- 27668026 TI - Improvement of Contrast Media Enhancement in CTA Evaluating Pulmonary Embolism by Utilizing 'Delayed' Bolus Tracking in the Descending Aorta. AB - BACKGROUND: As standard bolus triggering in the pulmonary trunk sometimes fails to achieve sufficient enhancement in the pulmonary arteries, the study investigates an alternative, 'delayed' position of the tracking ROI in the descending aorta. MATERIAL/METHODS: Retrospective analysis of 143 patients suspected of pulmonary embolism investigated with 3 different scanners (16 to 80 rows) in clinical routine. Bolus triggering with 120 hounsfield units (HU) was performed using the pulmonary trunk (n=70) or descending aorta (n=73) after application of 70 to 120 mL of contrast agent, Iomeprol 300. Student's t-test was applied to compare vascular enhancement. Additional factors were analysed by a regression analysis. RESULTS: Positioning of the tracking ROI in the descending aorta achieved a significantly higher contrast enhancement in the pulmonary trunk with a mean increase of 63 HU (p<0.001). CONCLUSIONS: In CTA, delayed acquisition by using the descending aorta for bolus triggering can improve the enhancement of the pulmonary trunk to investigate a pulmonary embolism. Furthermore, the scan protocol simultaneously allows to rule out aortic pathologies as an alternative cause for a similar clinical condition. PMID- 27668027 TI - Modified Right Heart Contrast Echocardiography Versus Traditional Method in Diagnosis of Right-to-Left Shunt: A Comparative Study. AB - BACKGROUND: The purpose of this study was to evaluate the reliability, effectiveness, and safety of modified right heart contrast transthoracic echocardiography (cTTE) in comparison with the traditional method. MATERIAL/METHODS: We performed a modified right heart cTTE using saline mixed with a small sample of patient's own blood. Samples were agitated with varying intensity. This study protocol involved microscopic analysis and patient evaluation. 1. Microscopic analysis: After two contrast samples had been agitated 10 or 20 times, they underwent a comparison of bubble size, bubble number, and red blood cell morphology. 2. Patient analysis: 40 patients with suspected RLS (right- to-left shunt) were enrolled. All patients underwent right heart contrast echocardiography. Oxygen saturation, transit time and duration, presence of RLS, change in indirect bilirubin and urobilinogen concentrations were compared afterward. RESULTS: Modified method generated more bubbles (P<0.05), but the differences in bubble size were not significant (P>0.05). Twenty-four patients were diagnosed with RLS (60%) using the modified method compared to 16 patients (40%) with the traditional method. The transit time of ASb20 group was the shortest (P<0.05). However, the duration time in this group was much longer (P<0.05). Also, in semi-quantitative analysis mean rank of RLS was higher after injecting the modified contrast agent agitated 20 times (P<0.05). CONCLUSIONS: Modified right heart contrast echocardiography is a reliable, effective and safe method of detecting cardiovascular RLS. PMID- 27668028 TI - Urethroscrotal Fistula: A Rare Cause of Scrotal Swelling. AB - BACKGROUND: Urethroscrotal fistula (USF) is an abnormal communication between the urethra and the scrotum. This rare abnormality may be iatrogenic or secondary to perforation of the urethra by a stone. After the passage of urine to the scrotum through the fistula, painless scrotal swelling develops, which disappears completely with manual compression, and voiding can be maintained in this way. Retrograde urethrography (RU) and voiding cystourethrography (VCU) are traditional diagnostic methods, but they have limitations, such as technical difficulties and inability to evaluate the surrounding tissues. Multidetector CT (MDCT), together with reformatted images, can provide valuable information about the surrounding tissues and associated pathologies. CASE REPORT: We present a case of a 36-year-old male patient who had painless scrotal swelling after cystolithotomy and urethral stone surgery. The patient indicated that the swelling disappeared after manual compression. A fistula between the bulbous urethra and the scrotum was discovered by MDCT. In our case, we believe that the fistula developed iatrogenically during stone excision or secondary to perforation of the urethra by a stone. CONCLUSIONS: As a rare pathology, urethroscrotal fistula should be considered in men with a history of urethral stone surgery and symptoms, including painless scrotal swelling, which can be manually compressed after voiding. PMID- 27668029 TI - Recruitment Strategies of Indian Men Who Have Sex with Men in the State of Maharashtra Into an Online Survey. AB - In this manuscript, we report lessons learned from our efforts to recruit Indian men and transgender women/hijras who have sex with men into an online cross sectional study. Between September 2013 and May 2014, we implemented a seven phased recruitment strategy that included the use of online and offline strategies to enroll a total of 449 participants into an online survey about recent sexual behavior and various psychosocial measures. The phases were implemented sequentially and cost-per-eligible participant was calculated. Using social media and collaborating with organizers of community events proved the most effective strategies for recruiting Indian MSM into online research. PMID- 27668030 TI - The Application of Frailty to the Modern Cardiac Risk Assessment: a Case-Based Review. AB - Cardiac risk assessment in aging patients poses a significant challenge to the practicing clinician, particularly when evaluating the use of invasive procedures. Frailty is a valuable risk marker that has been associated with worse outcomes in patients with coronary artery disease, heart failure, and aortic stenosis. Integrating the available frailty studies into cardiac risk assessments can help improve shared decision-making between physicians and their patients. In this review, we provide an up-to-date, case-based appraisal of the available clinical trial data focusing on the impact of frailty in patients with cardiovascular disease. PMID- 27668031 TI - Assessing methods for generalizing experimental impact estimates to target populations. AB - Randomized experiments are considered the gold standard for causal inference, as they can provide unbiased estimates of treatment effects for the experimental participants. However, researchers and policymakers are often interested in using a specific experiment to inform decisions about other target populations. In education research, increasing attention is being paid to the potential lack of generalizability of randomized experiments, as the experimental participants may be unrepresentative of the target population of interest. This paper examines whether generalization may be assisted by statistical methods that adjust for observed differences between the experimental participants and members of a target population. The methods examined include approaches that reweight the experimental data so that participants more closely resemble the target population and methods that utilize models of the outcome. Two simulation studies and one empirical analysis investigate and compare the methods' performance. One simulation uses purely simulated data while the other utilizes data from an evaluation of a school-based dropout prevention program. Our simulations suggest that machine learning methods outperform regression-based methods when the required structural (ignorability) assumptions are satisfied. When these assumptions are violated, all of the methods examined perform poorly. Our empirical analysis uses data from a multi-site experiment to assess how well results from a given site predict impacts in other sites. Using a variety of extrapolation methods, predicted effects for each site are compared to actual benchmarks. Flexible modeling approaches perform best, although linear regression is not far behind. Taken together, these results suggest that flexible modeling techniques can aid generalization while underscoring the fact that even state-of the-art statistical techniques still rely on strong assumptions. PMID- 27668032 TI - Teaching for All? Teach For America's Effects across the Distribution of Student Achievement. AB - This paper examines the effect of Teach For America (TFA) on the distribution of student achievement in elementary school. It extends previous research by estimating quantile treatment effects (QTE) to examine how student achievement in TFA and non-TFA classrooms differs across the broader distribution of student achievement. It also updates prior distributional work on TFA by correcting for previously unidentified missing data and estimating unconditional, rather than conditional QTE. Consistent with previous findings, results reveal a positive impact of TFA teachers across the distribution of math achievement. In reading, however, relative to veteran non-TFA teachers, students at the bottom of the reading distribution score worse in TFA classrooms, and students in the upper half of the distribution perform better. PMID- 27668033 TI - The Putative Chemosignal Androstadienone Makes Women More Generous. AB - Putative human chemosignals have been shown to influence mood states and emotional processing, but the connection between these effects and higher-order cognitive processing is not well established. This study utilized an economic game (Dictator Game) to test whether androstadienone (AND), an odorous compound derived from testosterone, impacts on altruistic behavior. We predicted that the female participants would act more generously in the AND condition, exhibiting a significant interaction effect between gender and AND on Dictator Game contributions. We also expected that the presence of AND should increase the positive mood of the female participants, compared to a control odor condition and also compared to the mood of the male participants. The results confirm our hypotheses: for women the subliminal perception of AND led to larger monetary donations, compared to a control odor, and also increased positive mood. These effects were absent or significantly weaker in men. Our findings highlight the capacity of human putative chemosignals to influence emotions and higher cognitive processes - in particular the processes used in the context of economic decisions - in a gender-specific way. PMID- 27668034 TI - Mechanisms and Clinical Application of Tetramethylpyrazine (an Interesting Natural Compound Isolated from Ligusticum Wallichii): Current Status and Perspective. AB - Tetramethylpyrazine, a natural compound from Ligusticum wallichii (Chuan Xiong), has been extensively used in China for cardiovascular and cerebrovascular diseases for about 40 years. Because of its effectiveness in multisystems, especially in cardiovascular, its pharmacological action, clinical application, and the structural modification have attracted broad attention. In this paper its mechanisms of action, the clinical status, and synthetic derivatives will be reviewed briefly. PMID- 27668036 TI - Allium cepa Extract and Quercetin Protect Neuronal Cells from Oxidative Stress via PKC-epsilon Inactivation/ERK1/2 Activation. AB - Oxidative stress plays an important role in the pathophysiology of various neurologic disorders. Allium cepa extract (ACE) and their main flavonoid component quercetin (QCT) possess antioxidant activities and protect neurons from oxidative stress. We investigated the underlying molecular mechanisms, particularly those linked to the antioxidant effects of the ACE. Primary cortical neuronal cells derived from mouse embryos were preincubated with ACE or QCT for 30 min and exposed to L-buthionine sulfoximine for 4~24 h. We found that ACE and QCT significantly decreased neuronal death and the ROS increase induced by L buthionine-S, R-sulfoximine (BSO) in a concentration-dependent manner. Furthermore, ACE and QCT activated extracellular signal-regulated kinase 1/2 (ERK1/2), leading to downregulation of protein kinase C-epsilon (PKC-epsilon) in BSO-stimulated neuronal cells. In addition, ACE and QCT decreased the phosphorylated levels of p38 mitogen-activated protein kinase. Our results provide new insight into the protective mechanism of ACE and QCT against oxidative stress in neuronal cells. The results suggest that the inactivation of PKC-epsilon induced by phosphorylating ERK1/2 is responsible for the neuroprotective effect of ACE and QCT against BSO-induced oxidative stress. PMID- 27668035 TI - Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells. AB - Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs), for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence of ex vivo expanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS scavenging compounds are crucial and promising therapeutic strategies for vascular repair. PMID- 27668039 TI - Evaluations of tropospheric aerosol properties simulated by the community earth system model with a sectional aerosol microphysics scheme. AB - A sectional aerosol model (CARMA) has been developed and coupled with the Community Earth System Model (CESM1). Aerosol microphysics, radiative properties, and interactions with clouds are simulated in the size-resolving model. The model described here uses 20 particle size bins for each aerosol component including freshly nucleated sulfate particles, as well as mixed particles containing sulfate, primary organics, black carbon, dust, and sea salt. The model also includes five types of bulk secondary organic aerosols with four volatility bins. The overall cost of CESM1-CARMA is approximately ~2.6 times as much computer time as the standard three-mode aerosol model in CESM1 (CESM1-MAM3) and twice as much computer time as the seven-mode aerosol model in CESM1 (CESM1-MAM7) using similar gas phase chemistry codes. Aerosol spatial-temporal distributions are simulated and compared with a large set of observations from satellites, ground-based measurements, and airborne field campaigns. Simulated annual average aerosol optical depths are lower than MODIS/MISR satellite observations and AERONET observations by ~32%. This difference is within the uncertainty of the satellite observations. CESM1/CARMA reproduces sulfate aerosol mass within 8%, organic aerosol mass within 20%, and black carbon aerosol mass within 50% compared with a multiyear average of the IMPROVE/EPA data over United States, but differences vary considerably at individual locations. Other data sets show similar levels of comparison with model simulations. The model suggests that in addition to sulfate, organic aerosols also significantly contribute to aerosol mass in the tropical UTLS, which is consistent with limited data. PMID- 27668041 TI - Welcome to the Seventh Annual Payers' Guide to New FDA Approvals. PMID- 27668038 TI - Properties of Flavonoids Isolated from the Bark of Eysenhardtia polystachya and Their Effect on Oxidative Stress in Streptozotocin-Induced Diabetes Mellitus in Mice. AB - Six new flavonoids 2',4'-dihydroxychalcone-6'-O-beta-d-glucopyranoside (1), alpha,3,2',4'-tetrahydroxy-4-methoxy-dihydrochalcone-3'-C-beta-glucopyranosy-6'-O beta-d-glucopyranoside (2), 7-hydroxy-5,8'-dimethoxy-6'alpha-l-rhamnopyranosyl-8 (3-phenyl-trans-acryloyl)-1-benzopyran-2-one (3), 6'7-dihydroxy-5,8-dimethoxy-8(3 phenyl-trans-acryloyl)-1-benzopyran-2-one (4), 9-hydroxy-3,8-dimethoxy-4 prenylpterocarpan (5), and alpha,4,4'-trihydroxydihydrochalcone-2'-O-beta-d glucopyranoside (6) were isolated from bark of Eysenhardtia polystachya. Antidiabetic activity of compounds 1-5 in terms of their cellular antioxidant and free radical scavenging and also in streptozotocin- (STZ-) induced diabetic mice was evaluated on liver transaminases, lipid peroxidation, total bilirubin, total protein, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (CSH Px), and glutathione reductase (GSH). Results indicated that 1-5 scavenged 2,2 diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (?OH), nitric oxide radicals (NO?), superoxide anion radical (O2?-), radical cation (ABTS?+), and hydrogen peroxide (H2O2) radical, and protection against H2O2 induced BSA damage was also observed. Furthermore, 1-5 showed ability to decrease the oxidative stress in H9c2 cell. Diabetic mice present high levels of lipid peroxide, total protein, SGPT, SGOT, ALP, and TB. However, treatment of STZ-induced diabetes in mice with 1-5 reduced levels of these enzymes leading to protector effect of liver. In addition, with treatment with 1-5, increases in radical scavenging enzymes of CSH-Px, SOD, GSH, and CAT have also been observed in diabetic mice. The antioxidant properties of compounds 1-5 are a promising strategy for ameliorating therapeutic effects by avoiding disorders in the normal redox reactions in healthy cells which consequently could alleviate complications of diabetes. PMID- 27668040 TI - Impacts of parameterized orographic drag on the Northern Hemisphere winter circulation. AB - A recent intercomparison exercise proposed by the Working Group for Numerical Experimentation (WGNE) revealed that the parameterized, or unresolved, surface stress in weather forecast models is highly model-dependent, especially over orography. Models of comparable resolution differ over land by as much as 20% in zonal mean total subgrid surface stress (tautot ). The way tautot is partitioned between the different parameterizations is also model-dependent. In this study, we simulated in a particular model an increase in tautot comparable with the spread found in the WGNE intercomparison. This increase was simulated in two ways, namely by increasing independently the contributions to tautot of the turbulent orographic form drag scheme (TOFD) and of the orographic low-level blocking scheme (BLOCK). Increasing the parameterized orographic drag leads to significant changes in surface pressure, zonal wind and temperature in the Northern Hemisphere during winter both in 10 day weather forecasts and in seasonal integrations. However, the magnitude of these changes in circulation strongly depends on which scheme is modified. In 10 day forecasts, stronger changes are found when the TOFD stress is increased, while on seasonal time scales the effects are of comparable magnitude, although different in detail. At these time scales, the BLOCK scheme affects the lower stratosphere winds through changes in the resolved planetary waves which are associated with surface impacts, while the TOFD effects are mostly limited to the lower troposphere. The partitioning of tautot between the two schemes appears to play an important role at all time scales. PMID- 27668037 TI - The Multiple Facets of Lutein: A Call for Further Investigation in the Perinatal Period. AB - Lutein may have important antioxidant actions in free-radical-mediated diseases, in addition to its well-known antioxidant and cytoprotective effects on macula and photoreceptors. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as lutein could help to prevent or at least to reduce oxidative stress related diseases in newborns. Since lutein is not synthesized by humans, the intake primarily depends on diet or supplementation. Newborns receive lutein exclusively from breast milk. Lutein supplementation in term newborns has been reported to reduce oxidative stress and increase antioxidant capacities in the first days of life. Innovative frontiers concerning lutein supplementation are orientated toward cardiometabolic health improvement and cognitive benefits. The safety of lutein as an antioxidant agent has been confirmed in experimental and clinical studies, but its routine use is not recommended in perinatal period. This review summarizes what is known about the role of lutein as an antioxidant and anti-inflammatory agent in animal model and humans. PMID- 27668042 TI - FDA Approvals of Brand-Name Prescription Drugs in 2015. AB - The drugs included in this review were approved by the US Food and Drug Administration (FDA) in 2015 and are grouped into the following categories: New Pharmaceuticals: New Molecular Entities and New Biologic License ApplicationsNew Combinations and New IndicationsNew Dosage Forms and New FormulationsNew Biosimilars, Vaccines, Viral Therapies, and Blood Products. PMID- 27668043 TI - Therapeutic Leap for Multiple Myeloma in 2015: Unprecedented FDA Drug Approvals. PMID- 27668044 TI - Aripiprazole Lauroxil (Aristada): Long-Acting Atypical Antipsychotic Injection Approved for the Treatment of Patients with Schizophrenia. PMID- 27668045 TI - Corlanor (Ivabradine), First HCN Channel Blocker, FDA Approved for the Treatment of Patients with Heart Failure. PMID- 27668046 TI - Cosentyx (Secukinumab): First IL-17A Antagonist Receives FDA Approval for Moderate-to-Severe Plaque Psoriasis. PMID- 27668047 TI - Darzalex (Daratumumab): First Anti-CD38 Monoclonal Antibody Approved for Patients with Relapsed Multiple Myeloma. PMID- 27668048 TI - Empliciti (Elotuzumab): First SLAMF7 Antibody Therapy Approved for the Treatment of Patients with Previously Treated Multiple Myeloma. PMID- 27668049 TI - Entresto (Sacubitril/Valsartan): First-in-Class Angiotensin Receptor Neprilysin Inhibitor FDA Approved for Heart Failure. PMID- 27668050 TI - Farydak (Panobinostat): First HDAC Inhibitor Approved for Patients with Relapsed Multiple Myeloma. PMID- 27668051 TI - Fycompa (Perampanel Hydrate) Receives Expanded Indication for Primary Generalized Tonic-Clonic Seizures. PMID- 27668052 TI - Imbruvica (Ibrutinib): First Drug Approved for the Treatment of Patients with Waldenstrom's Macroglobulinemia. PMID- 27668053 TI - Kyprolis (Carfilzomib) Received New Indications as Combination Therapy for Use in Relapsed and/or Refractory Multiple Myeloma. PMID- 27668054 TI - Lonsurf (Trifluridine plus Tipiracil): A New Oral Treatment Approved for Patients with Metastatic Colorectal Cancer. PMID- 27668056 TI - Nucala (Mepolizumab): First IL-5 Antagonist Monoclonal Antibody FDA Approved for Maintenance Treatment of Patients with Severe Asthma. PMID- 27668055 TI - Ninlaro (Ixazomib): First Oral Proteasome Inhibitor Approved for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. PMID- 27668057 TI - Pomalyst (Pomalidomide) Received a New Indication for Patients with Relapsed and/or Refractory Multiple Myeloma. PMID- 27668058 TI - Portrazza (Necitumumab), an IgG1 Monoclonal Antibody, FDA Approved for Advanced Squamous Non-Small-Cell Lung Cancer. PMID- 27668059 TI - Praluent (Alirocumab): First PCSK9 Inhibitor Approved by the FDA for Hypercholesterolemia. PMID- 27668060 TI - Repatha (Evolocumab): Second PCSK9 Inhibitor Approved by the FDA for Patients with Familial Hypercholesterolemia. PMID- 27668061 TI - Revlimid (Lenalidomide) Now FDA Approved as First-Line Therapy for Patients with Multiple Myeloma. PMID- 27668062 TI - Tresiba (Insulin Degludec Injection) and Ryzodeg 70/30 (Insulin Degludec and Insulin Aspart Injection): Two New Insulin Analogs for Glycemic Control in Diabetes Mellitus. PMID- 27668064 TI - Competition Heats Up in Rheumatoid Arthritis and Other Autoimmune Conditions. PMID- 27668063 TI - Zarxio (Filgrastim-sndz): First Biosimilar Approved in the United States. PMID- 27668065 TI - FULLY CONVOLUTIONAL NETWORKS FOR MULTI-MODALITY ISOINTENSE INFANT BRAIN IMAGE SEGMENTATION. AB - The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development. In the isointense phase (approximately 6-8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, resulting in extremely low tissue contrast and thus making the tissue segmentation very challenging. The existing methods for tissue segmentation in this isointense phase usually employ patch-based sparse labeling on single T1, T2 or fractional anisotropy (FA) modality or their simply-stacked combinations without fully exploring the multi-modality information. To address the challenge, in this paper, we propose to use fully convolutional networks (FCNs) for the segmentation of isointense phase brain MR images. Instead of simply stacking the three modalities, we train one network for each modality image, and then fuse their high-layer features together for final segmentation. Specifically, we conduct a convolution-pooling stream for multimodality information from T1, T2, and FA images separately, and then combine them in high-layer for finally generating the segmentation maps as the outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense phase brain images. Results showed that our proposed model significantly outperformed previous methods in terms of accuracy. In addition, our results also indicated a better way of integrating multi modality images, which leads to performance improvement. PMID- 27668066 TI - Self-reported discrimination and mental health among Asian Indians: Cultural beliefs and coping style as moderators. AB - The South Asian (SA) population has been underrepresented in research linking discrimination with health indicators; studies that focus on the unique cultural and psychosocial experiences of different SA subgroups are needed. The purpose of this study was to examine associations between self-reported discrimination and mental health among Asian Indians (AIs), and whether traditional cultural beliefs (believing that South Asian cultural traditions should be practiced in the US), coping style, and social support moderated these relationships. Asian Indians (N = 733) had been recruited from community-based sampling frames for the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study were included in this analysis. Multiple linear regression analyses were employed to evaluate relationships between discrimination and depressive symptoms, anger, and anxiety. Participants (men = 54%) were on average 55 years of age and had high levels of English proficiency, education, and income. Higher reports of discrimination were significantly associated with higher depressive symptoms, B = .27 (.05) p < .001, anger, B = .08 (.01), p < .001, and anxiety, B = .10 (.01), p < .001. Associations between discrimination and anger, B = -.005 (.002), p = .02, were weakest among those with stronger cultural beliefs. The link between discrimination and anxiety was attenuated by an active coping style, B = -.05 (.03), p = .04. In sum, self-reported discrimination appeared to adversely impact the mental health of AIs. Discrimination may be better coped with by having strong traditional cultural beliefs and actively managing experiences of discrimination. PMID- 27668068 TI - Blood thinners and gastrointestinal endoscopy. AB - As the number of diagnostic and therapeutic gastrointestinal endoscopies is increasing, and there is an increase in number of patients taking blood thinners, we are seeing more and more patients on blood thinners prior to endoscopic procedures. Gastrointestinal bleeding or thromboembolism can occur in this category of patients in the periendoscopic period. To better manage these patients, endoscopists should have a clear concept about the various blood thinners in the market. Patients' risk of thromboembolism off anticoagulation, and the risk of bleeding from endoscopic procedures should be assessed prior to endoscopy. The endoscopic procedure should be done when it is safe to do it. PMID- 27668067 TI - Current role of capsule endoscopy in Crohn's disease. AB - Capsule endoscopy (CE) currently plays an important role in Crohn's disease (CD). It is a noninvasive technique that has led to a breakthrough in the endoscopic diagnosis of diseases of the small intestine. Its superior diagnostic performance and excellent safety profile lead to its considerable acceptance on the part of the patient. This paper reviews current indications of CE in three stages of clinical practice: Suspected CD, unclassified colitis and its extensive role in diagnosed CD. The diagnostic and therapeutic impact of the results of CE on the monitoring of this disease is also reviewed. Knowledge of its applications, the interpretation of its results in an appropriate context and the existence of a validated endoscopic activity index could change the way in which these patients are managed. The definition of mucosal healing and postoperative recurrence by means of endoscopic scoring systems will endow CE with new applications in the management of CD in the near future. PMID- 27668070 TI - Review of small-bowel cleansing scales in capsule endoscopy: A panoply of choices. AB - Evaluation of the quality of small-bowel cleansing is required to assess the reliability of findings in capsule endoscopy (CE). Moreover, consensus regarding the need of intestinal preparation for CE remains to be achieved. The presence of multiple grading scales for small-bowel preparation in CE, which are time consuming and complicated, adds difficulty to the comparison of different small bowel cleansing regimens and their application in clinical practice. Nowadays, a validated scale universally accepted for grading small-bowel cleansing is lacking. In fact, there are numerous grading systems with very different technical characteristics, namely, the parameters and the portion of the CE video that are analyzed, the objectivity of the analysis, the lesser or greater dependency on the operator, and the validation of the score. The authors performed a review which aims to systematize and summarize currently available small-bowel grading scales in CE. PMID- 27668069 TI - Endoscopic management of post-bariatric surgery complications. AB - Understanding the technical constructs of bariatric surgery is important to the treating endoscopist to maximize effective endoluminal therapy. Post-operative complication rates vary widely based on the complication of interest, and have been reported to be as high as 68% following adjustable gastric banding. Similarly, there is a wide range of presenting symptoms for post-operative bariatric complications, including abdominal pain, nausea and vomiting, dysphagia, gastrointestinal hemorrhage, and weight regain, all of which may provoke an endoscopic assessment. Bleeding and anastomotic leak are considered to be early (< 30 d) complications, whereas strictures, marginal ulcers, band erosions, and weight loss failure or weight recidivism are typically considered late (> 30 d) complications. Treatment of complications in the immediate post operative period may require unique considerations. Endoluminal therapies serve as adjuncts to surgical and radiographic procedures. This review aims to summarize the spectrum and efficacy of endoscopic management of post-operative bariatric complications. PMID- 27668071 TI - Laparoscopic splenectomy for primary immune thrombocytopenia: Current status and challenges. AB - Primary immune thrombocytopenia (ITP) is an immune-mediated disorder affecting both adults and children, characterised by bleeding complications and low platelet counts. Corticosteroids are the first-line therapy for ITP, but only 20% 40% of cases achieve a stable response. Splenectomy is the main therapy for patients failing to respond to corticosteroids for decades, and about two-thirds of patients achieve a long-lasting response. Although some new drugs are developed to treat ITP as second-line therapies in recent years, splenectomy is still the better choice with less cost and more efficiency. Laparoscopic splenectomy (LS) for ITP proves to be a safe technique associated with lower morbidity and faster recovery and similar hematological response when compared to traditional open splenectomy. Based on the unified hematological outcome criteria by current international consensus, the response rate of splenectomy should be reassessed. So far, there are not widely accepted preoperative clinical indicators predicting favorable response to LS. Since the patients undergoing surgery take the risk of complications and poor hematological outcome, the great challenge facing the doctors is to identify a reliable biomarker for predicting long-term outcome of splenectomy which can help make the decision of operation. PMID- 27668072 TI - Predictors of suboptimal bowel preparation in asymptomatic patients undergoing average-risk screening colonoscopy. AB - AIM: To identify risk factors for a suboptimal preparation among a population undergoing screening or surveillance colonoscopy. METHODS: Retrospective review of the University of Michigan and Veteran's Administration (VA) Hospital records from 2009 to identify patients age 50 and older who underwent screening or surveillance procedure and had resection of polyps less than 1 cm in size and no more than 2 polyps. Patients with inflammatory bowel disease or a family history of colorectal cancer were excluded. Suboptimal procedures were defined as procedure preparations categorized as fair, poor or inadequate by the endoscopist. Multivariable logistic regression was used to identify predictors of suboptimal preparation. RESULTS: Of 4427 colonoscopies reviewed, 2401 met our inclusion criteria and were analyzed. Of our population, 16% had a suboptimal preparation. African Americans were 70% more likely to have a suboptimal preparation (95%CI: 1.2-2.4). Univariable analysis revealed that narcotic and tricyclic antidepressants (TCA) use, diabetes, prep type, site (VA vs non-VA), and presence of a gastroenterology (GI) fellow were associated with suboptimal prep quality. In a multivariable model controlling for gender, age, ethnicity, procedure site and presence of a GI fellow, diabetes [odds ratio (OR) = 2.3; 95%CI: 1.6-3.2], TCA use (OR = 2.5; 95%CI: 1.3-4.9), narcotic use (OR = 1.7; 95%CI: 1.2-2.5) and Miralax-Gatorade prep vs 4L polyethylene glycol 3350 (OR = 0.6; 95%CI: 0.4-0.9) were associated with a suboptimal prep quality. CONCLUSION: Diabetes, narcotics use and TCA use were identified as predictors of poor preparation in screening colonoscopies while Miralax-Gatorade preps were associated with better bowel preparation. PMID- 27668073 TI - Transanal endoscopic microsurgery as optimal option in treatment of rare rectal lesions: A single centre experience. AB - AIM: To analyze the outcomes of transanal endoscopic microsurgery (TEM) in the treatment of rare rectal condition like mesenchymal tumors, condylomas, endometriosis and melanoma. METHODS: We retrospectively reviewed a twenty-three years database. Fifty-two patients were enrolled in this study. The lesions were considered suitable for TEM if they were within 20 cm from the anus. All of them underwent an accurate preoperative workup consisting in clinical examination, total colonoscopy with biopsies, endoscopic ultrasonography, and pelvic computerized tomography or pelvic magnetic resonance imaging. Operative time, intraoperative complications, rate of conversion, tumor size, postoperative morbidity, mortality, the length of hospital stay, local and distant recurrence were analyzed. RESULTS: Among the 1328 patients treated by TEM in our department, the 52 patients with rectal abnormalities other than adenoma or adenocarcinoma represented 4.4%. There were 30 males (57.7%) and 22 females (42.3%). Mean age was 55 years (median = 60, range = 24-78). This series included 14 (26.9%) gastrointestinal stromal tumors, 21 neuroendocrine tumors (40.4%), 1 ganglioneuroma (1.9%), 2 solitary ulcers in the rectum (3.8%), 6 cases of rectal endometriosis (11.5%), 6 cases of rectal condylomatosis (11.5%) and 2 rectal melanomas (3.8%). Mean lesion diameter was 2.7 cm (median: 4, range: 0.4-8). Mean distance from the anal verge was 9.5 cm (median: 10, range: 4-15). One patient operated for rectal melanoma developed distant metastases and died two years after the operation. We experienced 2 local recurrences (3.8%) with an overall survival equal to 97.6% (95%CI: 95%-99%) at the end of follow-up and a disease free survival of 98% (95%CI: 96%-99%). CONCLUSION: We could conclude that TEM is an important therapeutical option for rectal rare conditions. PMID- 27668074 TI - Clinical relevance of aberrant polypoid nodule scar after endoscopic submucosal dissection. AB - AIM: To describe a series of patients with aberrant polypoid nodule scar developed after gastric endoscopic submucosal dissection (ESD), and to discuss its pathogenesis and clinical management. METHODS: We reviewed retrospectively the endoscopic database of two academic institutions located in Brazil and Japan and searched for all patients that underwent ESD to manage gastric neoplasms from 2003 to 2015. The criteria for admission in the study were: (1) successful en bloc ESD procedure with R0 and curative resection confirmed histologically; (2) postoperative endoscopic examination with identification of a polypoid nodule scar (PNS) at ESD scar; (3) biopsies of the PNS with hyperplastic or regenerative tissue, reviewed by two independent experienced gastrointestinal pathologists, one from each Institution. Data were examined for patient demographics, Helicobacter pylori status, precise neoplastic lesion location in the stomach, tumor size, histopathological assessment of the ESD specimen, and postoperative information including medical management, endoscopic and histological findings, and clinical outcome. RESULTS: A total of 14 patients (10 men/4 women) fulfilled the inclusion criteria and were enrolled in this study. One center contributed with 8 cases out of 60 patients (13.3%) from 2008 to 2015. The second center contributed with 6 cases (1.7%) out of 343 patients from 2003 to 2015. Postoperative endoscopic follow-up revealed similar findings in all patients: A protruded polypoid appearing nodule situated in the center of the ESD scar surrounded by convergence of folds. Biopsies samples were taken from PNS, and histological assessment revealed in all cases regenerative and hyperplastic tissue, without recurrent tumor or dysplasia. Primary neoplastic lesions were located in the antrum in 13 patients and in the angle in one patient. PNS did not develop in any patient after ESD undertaken for tumors located in the corpus, fundus or cardia. All patients have been followed systematically on an annual basis and no malignant recurrence in the ESD scar has been identified (mean follow-up period: 45 mo). CONCLUSION: PNS may occur after ESD for antral lesions and endoscopically look concerning, especially for the patient or the family doctor. However, as long as curative R0 resection was successfully achieved and histology demonstrates only regenerative and hyperplastic tissue, PNS should be viewed as a benign alteration that does not require any type of intervention, other than endoscopic surveillance. PMID- 27668075 TI - Diversifying Science: Intervention Programs Moderate the Effect of Stereotype Threat on Motivation and Career Choice. AB - Stereotypes influence academic interests, performance, and ultimately career goals. The long-standing National Institutes of Health Research Initiative for Scientific Enhancement (RISE) training program has been shown to be effective at retaining underrepresented minorities in science. We argue that programs such as RISE may alter the experience and impact of stereotype threat on academic achievement goals and future engagement in a scientific career. We report analyses of a national sample comparing RISE students with a propensity score matched control group over a 6-year period. Mediation analyses revealed that while RISE program membership did not buffer students from stereotype threat, it changed students' downstream responses and ultimately their academic outcomes. Nonprogram students were less likely than RISE students to persist in the sciences, partially because feelings of stereotype threat diminished their adoption of mastery goals. We discuss how these findings inform stereotype threat and goal orientation theories and provide insight into the success of intervention programs. PMID- 27668076 TI - Choco, Colombia: a hotspot of human biodiversity. AB - OBJECTIVE: Choco is a state located on the Pacific coast of Colombia that has a majority Afro-Colombian population. The objective of this study was to characterize the genetic ancestry, admixture and diversity of the population of Choco, Colombia. METHODOLOGY: Genetic variation was characterized for a sample of 101 donors (61 female and 40 male) from the state of Choco. Genotypes were determined for each individual via the characterization of 610,545 single nucleotide polymorphisms genome-wide. Haplotypes for the uniparental mitochondrial DNA (female) and Y-DNA (male) chromosomes were also determined. These data were used for comparative analyses with a number of worldwide populations, including putative ancestral populations from Africa, the Americas and Europe, along with several admixed American populations. RESULTS: The population of Choco has predominantly African genetic ancestry (75.8%) with approximately equal parts European (13.4%) and Native American (11.1%) ancestry. Choco shows relatively high levels of three-way genetic admixture, and far higher levels of Native American ancestry, compared to other New World African populations from the Caribbean and the United States. There is a striking pattern of sex-specific ancestry in Choco, with Native American admixture along the female lineage and European admixture along the male lineage. The population of Choco is also characterized by relatively high levels of overall genetic diversity compared to both putative ancestral populations and other admixed American populations. CONCLUSION: These results suggest a unique genetic heritage for the population of Choco and underscore the profound human genetic diversity that can be found in the region. PMID- 27668077 TI - Eu3+ doped alpha-sodium gadolinium fluoride luminomagnetic nanophosphor as a bimodal nanoprobe for high-contrast in vitro bioimaging and external magnetic field tracking applications. AB - Herein, we introduce a novel strategy for the synthesis of Eu3+ doped alpha sodium gadolinium fluoride (alpha-NaGd0.88F4:Eu0.123+) based luminomagnetic nanophosphors using hydrothermal route. The synthesized nanophosphor has exceptional luminescent and paramagnetic properties in a single host lattice, which is highly desirable for biomedical applications. This highly luminescent nanophosphor with an average particle size ~ 5+/-3 nm enables high-contrast fluorescent imaging with decreased light scattering. In vitro cellular uptake is shown by fluorescent microscopy that envisages the characteristic hypersensitive red emission of Eu3+ doped alpha-sodium gadolinium fluoride centered at 608 nm (5D0-7F2) upon 465 nm excitation wavelength. No apparent cytotoxicity is observed. Furthermore, time- resolved emission spectroscopy and SQUID magnetic measurements successfully demonstrate a photoluminescence decay time in microseconds and enhanced paramagnetic behavior respectively, which promises the applications of nanophosphors in biomedical studies. Hence, the obtained results strongly suggest that this nanophosphor could be potentially used as a bimodal nanoprobe for high-contrast in vitro bio-imaging of HeLa cells and external magnetic field tracking applications of luminomagnetic nanophosphors using permanent magnet. PMID- 27668078 TI - Local repair of stoma prolapse: Case report of an in vivo application of linear stapler devices. AB - INTRODUCTION: One of the most common late complications following stoma construction is prolapse. Although the majority of prolapse can be managed conservatively, surgical revision is required with incarceration/strangulation and in certain cases laparotomy and/or stoma reversal are not appropriate. This report will inform surgeons on safe and effective approaches to revising prolapsed stomas using local techniques. PRESENTATION OF CASE: A 58 year old female with an obstructing rectal cancer previously received a diverting transverse loop colostomy. On completion of neoadjuvant treatment, re-staging found new lung metastases. She was scheduled for further chemotherapy but incarcerated a prolapsed segment of her loop colostomy. As there was no plan to resect her primary rectal tumor at the time, a local revision was preferred. Linear staplers were applied to the prolapsed stoma in step-wise fashion to locally revise the incarcerated prolapse. Post-operative recovery was satisfactory with no complications or recurrence of prolapse. DISCUSSION: We detail in step-wise fashion a technique using linear stapler devices that can be used to locally revise prolapsed stoma segments and therefore avoid a laparotomy. The procedure is technically easy to perform with satisfactory post-operative outcomes. We additionally review all previous reports of local repairs and show the evolution of local prolapse repair to the currently reported technique. CONCLUSION: This report offers surgeons an alternative, efficient and effective option for addressing the complications of stoma prolapse. While future studies are needed to assess long-term outcomes, in the short-term, our report confirms the safety and effectiveness of this local technique. PMID- 27668079 TI - Postoperative washing of sutured wounds. AB - A best evidence topic was written according to the structured protocol. The three part question addressed was: [In patients undergoing closure of surgical wounds with sutures] does [keeping the wound dry for the first 48 h after closure] [reduce the incidence of surgical site infections (SSIs)]? 4 relevant papers were culled from the literature and appraised. The authors, date, country, population, study type, main outcomes, key results and study weaknesses were tabulated. Current NICE guidelines recommend cleaning surgical wounds with sterile saline only for the first 48 h following skin closure. We found no evidence that washing wounds with tap water during this period increases the incidence of SSIs compared to keeping them dry. Further randomised controlled trials will enable the construction of conclusive systematic reviews and meta-analyses. PMID- 27668080 TI - Morphological and physiological determinants of local adaptation to climate in Rocky Mountain butterflies. AB - Flight is a central determinant of fitness in butterflies and other insects, but it is restricted to a limited range of body temperatures. To achieve these body temperatures, butterflies use a combination of morphological, behavioural and physiological mechanisms. Here, we used common garden (without direct solar radiation) and reciprocal transplant (full solar radiation) experiments in the field to determine the thermal sensitivity of flight initiation for two species of Colias butterflies along an elevation gradient in the southwestern Rocky Mountains. The mean body temperature for flight initiation in the field was lower (24-26 degrees C) than indicated by previous studies (28-30 degrees C) in these species. There were small but significant differences in thermal sensitivity of flight initiation between species; high-elevation Colias meadii initiated flight at a lower mean body temperature than lower-elevation Colias eriphyle. Morphological differences (in wing melanin and thoracic setae) drive body temperature differences between species and contributed strongly to differences in the time and probability of flight and air temperatures at flight initiation. Our results suggest that differences both in thermal sensitivity (15% contribution) and in morphology (85% contribution) contribute to the differences in flight initiation between the two species in the field. Understanding these differences, which influence flight performance and fitness, aids in forecasting responses to climate change. PMID- 27668081 TI - Early exposure to ultraviolet-B radiation decreases immune function later in life. AB - Amphibians have declined dramatically worldwide. Many of these declines are occurring in areas where no obvious anthropogenic stressors are present. It is proposed that in these areas, environmental factors such as elevated solar ultraviolet-B (UV-B) radiation could be responsible. Ultraviolet-B levels have increased in many parts of the world as a consequence of the anthropogenic destruction of the ozone layer. Amphibian tadpoles are particularly sensitive to the damaging effects of UV-B radiation, with exposure disrupting growth and fitness in many species. Given that UV-B can disrupt immune function in other animals, we tested the hypothesis that early UV-B exposure suppresses the immune responses of amphibian tadpoles and subsequent juvenile frogs. We exposed Limnodynastes peronii tadpoles to sublethal levels of UV-B radiation for 6 weeks after hatching, then examined indices of immune function in both the tadpoles and the subsequent metamorphs. There was no significant effect of UV-B on tadpole leucocyte counts or on their response to an acute antigen (phytohaemagglutinin) challenge. However, early UV-B exposure resulted in a significant reduction in both metamorph leucocyte abundance and their response to an acute phytohaemagglutinin challenge. These data demonstrate that early UV-B exposure can have carry-over effects on later life-history traits even if the applied stressor has no immediately discernible effect. These findings have important implications for our understanding of the effects of UV-B exposure on amphibian health and susceptibility to diseases such as chytridiomycosis. PMID- 27668082 TI - 'Urinacoccus massiliensis' gen. nov. sp. nov., identified in urine sample of a 7 year-old boy hospitalized for dental care under general anaesthesia. AB - We report here the main characteristics of 'Urinacoccus massiliensis' gen. nov. sp. nov., strain FC2 (CSURP1992). This strain was isolated from the urine of an asymptomatic 7-year-old boy. PMID- 27668083 TI - Butyricimonas phoceensis sp. nov., a new anaerobic species isolated from the human gut microbiota of a French morbidly obese patient. AB - Butyricimonas phoceensis strain AT9 (= CSUR 1981 = DSM 100664) was isolated from a stool sample from a morbidly obese French patient living in Marseille using the culturomics approach. The genome of this Gram-negative-staining, anaerobic and non-spore forming rod bacillus is 4 736 949 bp long and contains 3947 protein coding genes. Genomic analysis identified 173 genes as ORFans (4.5%) and 1650 orthologous proteins (42%) not shared with the closest phylogenetic species, Butyricimonas virosa. Its major fatty acid was the branched acid iso-C15:0 (62.3%). PMID- 27668084 TI - A systematic review and meta-analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy? AB - BACKGROUND: The development of therapeutics is often characterized by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We tested the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in experimental glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a quality checklist. We calculated median survival ratios and used random effects meta-analysis to estimate efficacy. We explored effects of study design and quality and searched for evidence of publication bias. RESULTS: We identified 193 publications using gene therapy in experimental glioma, including 6,366 animals. Overall, gene therapy improved median survival by a factor of 1.60 (95% CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity. We observed similar findings in a data subset limited to the most common gene therapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment for glioma. Nevertheless, we have identified areas for improvement in conduct and reporting of studies, and we provide a basis for sample size calculations. Further work should focus on genes of interest in paradigms recapitulating human disease. This might improve the translation of such therapies into the clinic. PMID- 27668085 TI - Perceived helpfulness of the individual components of a behavioural weight loss program: results from the Hopkins POWER Trial. AB - BACKGROUND: Behavioural weight loss programs are effective first-line treatments for obesity and are recommended by the US Preventive Services Task Force. Gaining an understanding of intervention components that are found helpful by different demographic groups can improve tailoring of weight loss programs. This paper examined the perceived helpfulness of different weight loss program components. METHODS: Participants (n = 236) from the active intervention conditions of the Practice-based Opportunities for Weight Reduction (POWER) Hopkins Trial rated the helpfulness of 15 different components of a multicomponent behavioural weight loss program at 24-month follow-up. These ratings were examined in relation to demographic variables, treatment arm and weight loss success. RESULTS: The components most frequently identified as helpful were individual telephone sessions (88%), tracking weight online (81%) and coach review of tracking (81%). The component least frequently rated as helpful was the primary care providers' general involvement (50%). Groups such as older adults, Blacks and those with lower education levels more frequently reported intervention components as helpful compared with their counterparts. DISCUSSION: Weight loss coaching delivered telephonically with web support was well received. Findings support the use of remote behavioural interventions for a wide variety of individuals. PMID- 27668087 TI - Frequency of self-weighing and weight loss outcomes within a brief lifestyle intervention targeting emerging adults. AB - BACKGROUND: Frequent self-weighing is associated with better weight loss and maintenance among adults. Emerging adults ages 18-25 rarely enroll in behavioural weight loss trials, and thus, little is known about their willingness to engage in frequent self-weighing and its association with weight loss in this age group. PURPOSE: The purpose of this study is to examine the frequency of self-weighing among 18-25-year-old over the course of a brief lifestyle intervention and to determine the association between frequent self-weighing and weight loss. METHODS: Emerging adults (EA) ages 18-25 [N = 52, 54% racial/ethnic minority, 79% female, BMI = 34.2 (5.4)] enrolled in a 3-month lifestyle intervention with structure and content modified for EA. Benefits of frequent self-weighing were presented; participants were encouraged to weigh themselves at least weekly and no more than daily. Assessments occurred at baseline and post-treatment (3 months). RESULTS: At baseline, a majority of participants (63.5%) reported self weighing less than once a week. Frequency of self-weighing increased over treatment (p < 0.001), with 42.9% weighing weekly and 38.2% weighing several times per week or more (i.e. frequent self-weighing) at 3 months. Frequent self weighing was associated with greater weight loss (p = 0.03) and greater likelihood of achieving 5% weight loss (p = 0.01) at post-treatment. CONCLUSIONS: Frequent self-weighing may be a viable approach to promoting self-regulation during the high-risk developmental period of emerging adulthood. Consistent with findings among other adult samples, frequent self-weighing was associated with greater weight losses. PMID- 27668086 TI - Cognitive dysfunction predicts poorer emotion recognition in bariatric surgery candidates. AB - OBJECTIVE: Deficits in traditional cognitive domains (e.g. executive function and memory) are common in persons with severe obesity, but it is unclear if this pattern of dysfunction extends to social cognition. The present study examined whether cognitive impairment was associated with poorer emotion recognition in bariatric surgery candidates. METHODS: One hundred sixteen bariatric surgery candidates (mean age = 43.62 +/- 11.03; 81% female) completed the computerized Integneuro test battery as part of a larger study visit. In addition to assessing traditional cognitive domains, the Integneuro also includes an emotion recognition measure. This task presents 48 faces (eight different individuals depicting neutral, happiness, fear, sadness, anger and disgust), and participants must choose the correct verbal label from six expression options. Number of correct responses and average reaction time for correct responses served as primary dependent variables. RESULTS: Stepwise multiple regression analyses revealed that older age, more maze errors, and history of hypertension predicted less accuracy in emotion recognition (adjusted R2 = .22, F[3, 111] = 11.86, p < .001) and that slower switching of attention-digits, worse long-delay recall, and older age predicted speed of responses (adjusted R2 = .26, F[3, 111] = 13.00, p < .001). DISCUSSION: Results show that cognitive dysfunction is associated with poorer performance on a computerized test of emotion recognition, consistent with those in persons with a range of psychiatric and neurological disorders. Additional work is needed to clarify the mechanisms and functional impact of these impairments, especially in relation to weight loss following bariatric surgery. PMID- 27668088 TI - Six1 is down-regulated in end-stage human dilated cardiomyopathy independently of Ezh2. AB - BACKGROUND: Recently, it was shown that a knock-out (KO) of the polycomb histone methyltransferase Ezh2 leads to cardiac hypertrophy in mice, which was driven by the homeodomain transcription factor Six1. Here, we analyzed the expression of Six1 and its regulating factor Ezh2 in cardiac tissue of patients with end-stage dilative cardiomyopathy (DCM). METHODS: Tissue samples of patients with end-stage DCM (n = 35) were compared with controls (n = 12) for the protein expression of Ezh1, Ezh2, Six1, and a marker of protein expression p70S6K. RESULTS: Contrary to the Ezh2-KO mouse model, we found a down-regulation of Six1 (26%) and an up regulation of Ezh2 (76%) in DCM hearts, (both P < 0.05). Expression of Ezh2 and Six1 did not correlate in human tissue (DCM: r2: 0.03, P = 0.31 and donor: r2: 0.05, P = 0.45). Expression of Six1 weakly correlated with left ventricular end systolic diameter and fractional shortening. In DCM, Six1 also showed a positive correlation to the expression of the ribosomal protein p70S6K (r: 0.39, P = 0.029), which is involved in protein synthesis. This correlation was not seen in donor tissue, which showed a trend for a negative correlation (r: -0.49, P = 0.08). CONCLUSION: Our data indicate that the Ezh2/Six1 axis might be involved in human DCM. However, Six1 expression may be regulated by factors other than Ezh2, and more research is needed to determine the precise role of Ezh2/Six1 in human DCM. PMID- 27668089 TI - Higher risk for incident heart failure and cardiovascular mortality among community-dwelling octogenarians without pneumococcal vaccination. AB - AIMS: Octogenarians have the highest incidence of heart failure (HF) that is not fully explained by traditional risk factors. We explored whether lack of pneumococcal vaccination is associated with higher risk of incident HF among octogenarians. METHODS AND RESULTS: In the Cardiovascular Health Study (CHS), 5290 community-dwelling adults, >=65 years of age, were free of baseline HF and had data on pneumococcal vaccination. Of these, 851 were octogenarians, of whom, 593 did not receive pneumococcal vaccination. Multivariable-adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for associations of lack of pneumococcal vaccination with incident HF and other outcomes during 13 years of follow-up were estimated using Cox regression models, adjusting for demographics and other HF risk factors including influenza vaccination. Octogenarians had a mean (+/-SD) age of 83 (+/-3) years; 52% were women and 17% African American. Overall, 258 participants developed HF and 662 died. Lack of pneumococcal vaccination was associated with higher relative risk of incident HF (aHR, 1.37; 95% CI, 1.01-1.85; P = 0.044). There was also higher risk for all-cause mortality (aHR, 1.23; 95% CI, 1.02-1.49; P = 0.028), which was mostly driven by cardiovascular mortality (aHR, 1.45; 95% CI, 1.06-1.98; P = 0.019). Octogenarians without pneumococcal vaccination had a trend toward higher risk of hospitalization due to pneumonia (aHR, 1.34; 95% CI, 0.99-1.81; P = 0.059). These associations were not observed among those 65-79 years of age. CONCLUSIONS: Among community-dwelling octogenarians, lack of pneumococcal vaccination was associated with a significantly higher independent risk of incident HF and mortality, and trend for higher pneumonia hospitalization. PMID- 27668091 TI - Cancer nanomedicine: Is targeting our target? AB - Nanomedicine may have a delivery problem. Rigorous, realistic and holistic rethinking is needed to improve nanomedicine performance and increase patient benefit. PMID- 27668090 TI - A Method to Identify and Analyze Biological Programs through Automated Reasoning. AB - Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function. PMID- 27668092 TI - Cellulosimicrobium funkei-like enhances the growth of Phaseolus vulgaris by modulating oxidative damage under Chromium(VI) toxicity. AB - Contamination of agriculture land by heavy metals is a worldwide risk that has sped up noticeably since the beginning of the industrial revolution. Hence, there arise the demands of heavy metal tolerant plant growth promoting bacterial strains for specific metal contaminated agricultural sites restoration. In this study, 36 bacterial isolates were screened out from the rhizospheric soil of Phaseolus vulgaris. Among these, two bacterial strains AR6 and AR8 were selected based on their higher Cr(VI) tolerance (1200 and 1100 MUg/mL, respectively) and the maximum production of plant growth promoting substances. In the molecular characterization study, both the bacterial strains showed 99% homology with Cellulosimicrobium funkei KM032184. In greenhouse experiments, the exposure of Cr(VI) to P.vulgaris inhibited the growth and photosynthetic pigments and increased the enzymatic and non-enzymatic antioxidant expressions. However, rhizosphere bacterial inoculations alleviated the negative effect of Cr(VI) and enhanced the seed germination rate (89.54%), shoot (74.50%),root length (60%), total biomass (52.53%), chlorophyll a (15.91%), chlorophyll b (17.97%), total chlorophyll (16.58%) and carotenoid content (3.59%). Moreover, bacterial inoculations stabilized and modulated the antioxidant system of P. vulgaris by reducing the accumulation of Cr in plant tissues. The present finding shows the Cr(VI) tolerance and plant growth promoting properties of the rhizosphere bacterial strains which might make them eligible as biofertilizer of metal contaminated soils. PMID- 27668093 TI - Active Tuberculosis Case Finding in Port-au-Prince, Haiti: Experiences, Results, and Implications for Tuberculosis Control Programs. AB - Background. Haiti has the highest tuberculosis (TB) prevalence in the Americas with 254 cases per 100,000 persons. Case detection relies on passive detection and TB services in many regions suffer from poor diagnostic and clinical resources. Methods. Mache Chache ("Go and Seek") was a TB REACH Wave 3 funded TB case finding project in Port-au-Prince between July 2013 and September 2014, targeting four intervention areas with insufficient TB diagnostic performance. Results. Based on a verbal symptom screen emphasizing the presence of cough, the project identified 11,150 (11.75%) of all screened persons as TB subjects and 2.67% as smear-positive (SS+) TB cases. Enhanced case finding and strengthening of laboratory services led to a 59% increase in bacteriologically confirmed cases in the evaluation population. In addition, smear grades dropped significantly, suggesting earlier case detection. Xpert(r) MTB/RIF was successfully introduced and improved TB diagnosis in HIV-infected, smear-negative clinic patients, but not in HIV-negative, smear-negative TB suspects in the community. However, the number needed to screen for one additional SS+ case varied widely between clinic and community screening activities. Conclusion. Enhanced and active TB case finding in Haiti can improve TB diagnosis and care. However, screening algorithms have to be tailored to individual settings, necessitating long-term commitment. PMID- 27668095 TI - Epidural Analgesia with Ropivacaine during Labour in a Patient with a SCN5A Gene Mutation. AB - SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour. PMID- 27668096 TI - Successful Retrieval of a Dismembered Central Venous Catheter Stuck to the Right Pulmonary Artery Using a Stepwise Approach. AB - Recent advances in anticancer chemotherapy have resulted in an increase in the number of patients requiring a central venous port catheter, and the incidence of catheter pinch-off syndrome has been increasing. Catheter pinch-off syndrome is a rare and unusual complication. It is difficult to retrieve dislodged catheters from the pulmonary artery, especially if the catheter is stuck to the peripheral pulmonary artery. We herein describe the successful removal of a catheter stuck in the pulmonary artery with a stepwise approach. First, a pigtail catheter was used to tug the dislodged catheter in order to free the unilateral end. Then, a gooseneck snare was used to catch and pull the catheter out of the patient. The key to success is to free the end of the catheter. PMID- 27668094 TI - Prisms to Shift Pain Away: Pathophysiological and Therapeutic Exploration of CRPS with Prism Adaptation. AB - Complex Regional Pain Syndrome (CRPS) is an invalidating chronic condition subsequent to peripheral lesions. There is growing consensus for a central contribution to CRPS. However, the nature of this central body representation disorder is increasingly debated. Although it has been repeatedly argued that CRPS results in motor neglect of the affected side, visual egocentric reference frame was found to be deviated toward the pain, that is, neglect of the healthy side. Accordingly, prism adaptation has been successfully used to normalize this deviation. This study aimed at clarifying whether 7 CRPS patients exhibited neglect as well as exploring the pathophysiological mechanisms of this manifestation and of the therapeutic effects of prism adaptation. Pain and quality of life, egocentric reference frames (visual and proprioceptive straight ahead), and neglect tests (line bisection, kinematic analyses of motor neglect and motor extinction) were repeatedly assessed prior to, during, and following a one-week intense prism adaptation intervention. First, our results provide no support for visual and motor neglect in CRPS. Second, reference frames for body representations were not systematically deviated. Third, intensive prism adaptation intervention durably ameliorated pain and quality of life. As for spatial neglect, understanding the therapeutic effects of prism adaptation deserves further investigations. PMID- 27668097 TI - Interventricular Septal Hematoma and Coronary-Ventricular Fistula: A Complication of Retrograde Chronic Total Occlusion Intervention. AB - Interventricular septal hematoma is a rare complication of retrograde chronic total occlusion (CTO) percutaneous coronary interventions (PCI) with a typically benign course. Here we report two cases of interventricular septal hematoma and coronary-cameral fistula development after right coronary artery (RCA) CTO-PCI using a retrograde approach. Both were complicated by development of ST-segment elevation and chest pain. One case was managed actively and the other conservatively, both with a favorable outcome. PMID- 27668098 TI - Orthodontic and Orthognathic Surgical Treatment of a Pediatric OSA Patient. AB - A case report is presented which demonstrates the effectiveness of comprehensive orthodontic treatment combined with orthognathic surgery in the correction of malocclusion and reduction in the sequelae of Obstructive Sleep Apnea (OSA). The patient's severe OSA was improved to very mild as evaluated by full overnight polysomnogram. The orthodontic treatment included the expansion of both dental arches and mandibular advancement surgery. There was significant improvement in the patient's sleep continuity and architecture with the elimination of obstructive apneas. PMID- 27668100 TI - Medication-Related Osteonecrosis of Jaws: A Low-Level Laser Therapy and Antimicrobial Photodynamic Therapy Case Approach. AB - Medication-related osteonecrosis of the jaws (MRONJ) can be considered an inability of the alveolar bone to respond to an injury, which frequently leads to severe local and systemic complications. Once the problem is installed, dentist must use all therapeutic approaches recommended. This manuscript reports a successful management of MRONJ handled with antibiotics, conservative debridement, low-level laser therapy (LLLT), and photodynamic therapy (PDT) up to 12 months. As healing of MRONJ may be very slow, combined therapeutic approaches are required. Besides the recommended conventional treatment protocol, LLLT and PDT are important tools to contribute to healing and improvement of patient's quality of life. PMID- 27668099 TI - Esthetic Rehabilitation through Crown Lengthening Surgery and Conservative CAD/CAM Veneers: A Multidisciplinary Case Report. AB - This case report describes a successful multidisciplinary approach used to improve the smile esthetics of a patient presenting with excessive gingival display, asymmetric gingival margins, and small upper anterior teeth and lower anterior teeth. The treatment combined esthetic crown lengthening, dental bleaching, and restorative dentistry using CAD/CAM veneer. The 6-month follow-up examination confirmed the stability of the modification and absence of adverse effects. PMID- 27668101 TI - A Ruptured Ectopic Pregnancy Presenting with a Negative Urine Pregnancy Test. AB - A negative urine pregnancy test in the emergency department traditionally excludes the diagnosis of pregnancy. We report a rare case of ruptured ectopic pregnancy in a patient with a negative urine pregnancy test but with a serum beta human chorionic gonadotropin (beta-hCG) of 10 mIU/mL. The patient developed hemoperitoneum and required laparoscopy by Obstetrics and Gynecology (OB/Gyn). This case highlights the fallibility of the urine pregnancy test in diagnosing early pregnancy. PMID- 27668102 TI - A Unique Case of Mycophenolate Induced Colitis after 10 Years of Use. AB - A 31-year-old female with a history of lupus nephritis on Hydroxychloroquine, Prednisone, and Mycophenolate Mofetil (MMF) for 10 years presented to the hospital for ankle swelling. On day four, she started to have severe, nonbloody, watery diarrhea with abdominal distension and tenderness. Stool PCR was negative for C. difficile. CT abdomen/pelvis showed gaseous distension of the colon without any obstruction. Flexible sigmoidoscopy revealed a normal looking mucosa. Histopathology showed crypt atrophy and increased crypt apoptosis, consistent with MMF colitis. The diarrhea resolved three days after stopping MMF. Although generally well tolerated, diarrhea is a common side effect of MMF. Most cases occur in the first six months of starting MMF. This case is unique because it describes MMF colitis in lupus after more than 10 years. Thus, MMF colitis should be considered as a differential in patients taking it, regardless of the duration of use. PMID- 27668103 TI - Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma. AB - We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP) after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case. PMID- 27668104 TI - Acute Myeloid Leukemia Relapse Presenting as Complete Monocular Vision Loss due to Optic Nerve Involvement. AB - Acute myeloid leukemia (AML) involvement of the central nervous system is relatively rare, and detection of leptomeningeal disease typically occurs only after a patient presents with neurological symptoms. The case herein describes a 48-year-old man with relapsed/refractory AML of the mixed lineage leukemia rearrangement subtype, who presents with monocular vision loss due to leukemic eye infiltration. MRI revealed right optic nerve sheath enhancement and restricted diffusion concerning for nerve ischemia and infarct from hypercellularity. Cerebrospinal fluid (CSF) analysis showed a total WBC count of 81/mcl with 96% AML blasts. The onset and progression of visual loss were in concordance with rise in peripheral blood blast count. A low threshold for diagnosis of CSF involvement should be maintained in patients with hyperleukocytosis and high-risk cytogenetics so that prompt treatment with whole brain radiation and intrathecal chemotherapy can be delivered. This case suggests that the eye, as an immunoprivileged site, may serve as a sanctuary from which leukemic cells can resurge and contribute to relapsed disease in patients with high-risk cytogenetics. PMID- 27668105 TI - Subdiaphragmatic Renal Ectopia: Case Report and Review of the Literature. AB - Background. We report the case of a male infant whose right kidney migrated to an ectopic position after birth. The migration of a kidney in postnatal life without any symptoms has not been reported in literature so far. Case Presentation. In a series of antenatal and the first postnatal ultrasound scans, the right kidney was normally located within the right renal fossa. During the first 3 months of life, the kidney migrated to a subdiaphragmatic position. This was confirmed on MRI scan. The infant was asymptomatic with normal renal function and blood pressure. Conclusion. Postnatal migration of a kidney has been described in cases of diaphragmatic hernia or nephroptosis. In this report, we describe a case of kidney migration where there were no underlying anatomical defects to provide an explanation for the kidney migration. This is the first report in literature of a case of postnatal migration of a kidney. PMID- 27668106 TI - Atypical Features in a Large Turkish Family Affected with Friedreich Ataxia. AB - Here, we describe the clinical features of several members of the same family diagnosed with Friedreich ataxia (FRDA) and cerebral lesions, demyelinating neuropathy, and late-age onset without a significant cardiac involvement and presenting with similar symptoms, although genetic testing was negative for the GAA repeat expansion in one patient of the family. The GAA repeat expansion in the frataxin gene was shown in all of the family members except in a young female patient. MRI revealed arachnoid cysts in two patients; MRI was consistent with both cavum septum pellucidum-cavum vergae and nodular signal intensity increase in one patient. EMG showed demyelinating sensorimotor polyneuropathy in another patient. The GAA expansion-negative 11-year-old female patient had mental-motor retardation, epilepsy, and ataxia. None of the patients had significant cardiac symptoms. Description of FRDA families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease. Furthermore, the genetic heterogeneity observed in this family draws attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before delivering comprehensive genetic counseling. PMID- 27668107 TI - Marchiafava-Bignami and Alcohol Related Acute Polyneuropathy: The Cooccurrence of Two Rare Entities. AB - Objectives. The aim of this article is to represent the first reported case with cooccurrence of two rare alcohol related complications. Case Report. We report a 38-year-old man with chronic alcoholism who presented with both cranial and peripheral nerve palsy. On MRI examination characteristic findings of Marchiafava Bignami disease were recognized. Discussion. Marchiafava-Bignami disease (MBD) is a rare complication of long-term, heavy alcohol abuse that has characteristic MRI findings. Acute alcohol related polyneuropathy (AARP) is another rare and not well-understood complication of chronic alcohol abuse. We could not find any previous report of the cooccurrence of these two complications in the literature. PMID- 27668108 TI - A Patient with Eight Intracranial Aneurysms: Endovascular Treatment in Two Sessions. AB - The frequency of multiple intracranial aneurysms seen in patients with or without subarachnoid hemorrhage is high. The advancement of the endovascular technique and devices has ensured that endovascular treatment of intracranial aneurysms is the first choice in most cases, especially in unruptured ones. Different combinations of treatment modalities and techniques can be used in the management of multiple aneurysms. But in selected patients without subarachnoid hemorrhage, treatment of all aneurysms in one or more sessions with endovascular techniques is less traumatic than that with surgery. In the literature, the maximum number of aneurysms in one patient treated endovascularly and/or surgically is seven. In this case report, we present, with a review of the literature, a patient with eight intracranial aneurysms, all of which were treated in two sessions with various endovascular techniques. A 40-year-old female patient was admitted due to headache. Angiography showed eight aneurysms in the posterior circulation and, bilaterally, in the anterior circulation. All aneurysms were treated endovascularly in two sessions. In the treatment of the aneurysms, different endovascular techniques were used including flow diverters stents, stent-assisted coiling, Y-stent-assisted coiling, and coiling alone. PMID- 27668109 TI - Apocrine Adenocarcinoma of the Vulva: A Case Report and Review of the Literature. AB - Primary vulvar adenocarcinomas are very rare. We describe the rare case of primary vulvar apocrine adenocarcinoma, a histologically rare subtype of vulvar adenocarcinoma. A 57-year-old Japanese woman presented with an enlarging vulvar mass. A dark-red, hemorrhagic, ulcerated tumor was on the right side of the anterior labial commissure measuring approximately 3.5 * 3.5 cm. Preoperative biopsy showed poorly differentiated carcinoma with partial differentiation to adenocarcinoma. Systemic examination revealed lymph node metastases in both inguinal regions and no other primary source. We performed radical vulvectomy and bilateral inguinal and pelvic lymphadenectomy. Histopathologic diagnosis was apocrine adenocarcinoma of the vulva with inguinal lymph node metastases, pT1bN2bM0. Surgical margins were negative. The patient received no adjuvant chemotherapy or radiation. Inguinal lymph node recurrence occurred after six months. Reresection and adjuvant tomotherapy were performed. After a further 12 months of observation, no rerecurrence was observed. The patient is now on follow up. PMID- 27668110 TI - Complex Laparoscopic Myomectomy with Severe Adhesions Performed with Proper Preventive Measures and Power Morcellation Provides a Safe Choice in Certain Infertility Cases. AB - Laparoscopic myomectomy offers a real benefit to infertile patients with uterine fibroids and peritoneal adhesions. The procedure requires a skilled surgeon and laparoscopy technique to minimize adhesion formation and other proven benefits. Restrictions arise since this procedure requires power morcellation for fibroid tissue extraction. Two years ago, the Food and Drug Administration in the United States of America (FDA) issued the alert on power morcellation for uterine leiomyomas, addressing the risk of malignant cell spreading within the abdominal cavity (actual risk assessment from 1 in 360 to 1 in 7400 cases). We review a 30 year-old female, without previous gestations, hypermenorrhea, intermenstrual bleeding, and chronic pelvic pain. Transvaginal ultrasound reports multiple fibroids in the right portion of a bicornuate uterus. Relevant history includes open myomectomy 6 years before and a complicated appendectomy, developing peritonitis within a year. Laparoscopy revealed multiple adhesions blocking uterine access, a bicornuate uterus, and myomas in the expected site. Myomectomy was performed utilizing power morcellation with good results. FDA recommendations have diminished this procedure's selection, converting many to open variants. This particular case was technically challenging, requiring morcellation, and safety device deployment was impossible, yet the infertility issue was properly addressed. Patient evaluation, safety measures, and laparoscopy benefits may outweigh the risks in particular cases as this one. PMID- 27668111 TI - Florid Cystic Endosalpingiosis (Mullerianosis) in Pregnancy. AB - Cystic endosalpingiosis refers to the existence of heterotopic cystic mullerian tissue resembling structures of the fallopian tubes. We report a case of florid cystic endosalpingiosis discovered in a pregnant woman during a scheduled cesarean section and review the current knowledge of this disease. A 30-year-old woman with a twin pregnancy attended the hospital day unit at term. The first twin was in a breech presentation and a cesarean section was scheduled. During the procedure the uterine fundus and part of the body were seen completely seeded with multitude of cyst-like structures resembling hydatids of Morgagni. The immunohistochemistry analysis showed a positive expression for PAX8 (Box-8), CK7, and estrogen and progesterone receptors. The lesions did not disappear after pregnancy. Cystic endosalpingiosis should be always borne in mind, even in pregnancy, when it comes to making the differential diagnosis of a pelvic or systemic multicystic mass. PMID- 27668112 TI - Bilateral Diabetic Knee Neuroarthropathy in a Forty-Year-Old Patient. AB - Diabetic osteoarthropathy is a rare cause of neuropathic joint disease of the knee; bilateral involvement is even more exceptional. Diagnosis is often made late due to its unspecific symptoms and appropriate surgical management still needs to be defined, due to lack of evidence because of the disease's low incidence. We report the case of a forty-year-old woman with history of diabetes type I who developed bilateral destructive Charcot knee arthropathy. Bilateral total knee arthroplasty was performed in order to achieve maximal functional outcome. Follow-up was marked by bilateral tibial periprosthetic fractures treated by osteosynthesis with a satisfactory outcome. The diagnosis of Charcot arthropathy should always be in mind when dealing with atraumatic joint destruction in diabetic patients. Arthroplasty should be considered as an alternative to arthrodesis in bilateral involvement in young patients. PMID- 27668113 TI - Persistent Down-Beating Torsional Positional Nystagmus: Posterior Semicircular Canal Light Cupula? AB - A 16-year-old boy with rotatory positional vertigo and nausea, particularly when lying down, visited our clinic. Initially, we observed vertical/torsional (downward/leftward) nystagmus in the supine position, and it did not diminish. In the sitting position, nystagmus was not provoked. Neurological examinations were normal. We speculated that persistent torsional down-beating nystagmus was caused by the light cupula of the posterior semicircular canal. This case provides novel insights into the light cupula pathophysiology. PMID- 27668114 TI - Bilateral Vocal Cord Paralysis and Cervicolumbar Radiculopathy as the Presenting Paraneoplastic Manifestations of Small Cell Lung Cancer: A Case Report and Literature Review. AB - Introduction. Bilateral vocal cord paralysis (BVCP) is a potential medical emergency. The Otolaryngologist plays a crucial role in the diagnosis and management of BVCP and must consider a broad differential diagnosis. We present a rare case of BVCP secondary to anti-Hu paraneoplastic syndrome. Case Presentation. A 58-year-old female presented to an Otolaryngology clinic with a history of progressive hoarseness and dysphagia. Flexible nasolaryngoscopy demonstrated BVCP. Cross-sectional imaging of the brain and vagus nerves was negative. An antiparaneoplastic antibody panel was positive for anti-Hu antibodies. This led to an endobronchial biopsy of a paratracheal lymph node, which confirmed the diagnosis of small cell lung cancer. Conclusion. Paraneoplastic neuropathy is a rare cause of BVCP and should be considered when more common pathologies are ruled out. This is the second reported case of BVCP as a presenting symptom of paraneoplastic syndrome secondary to small cell lung cancer. PMID- 27668115 TI - Case of Chronic Otitis Media with Intracranial Complication and Contralateral Extracranial Presentation. AB - Intracranial complications of chronic otitis media have been on the decline with advent of antibiotics. Septic thrombosis of the sigmoid sinus is rarer compared to commoner complications such as otogenic brain abscesses and meningitis. This patient presented with recurrent infection after left mastoidectomy secondary to cholesteatoma and a contralateral internal jugular vein thrombosis with parapharyngeal abscess, which was drained. He recovered well postoperatively with antibiotics. PMID- 27668116 TI - Recurrent Midgut Bleeding due to Jejunal Angioleiomyoma. AB - Angioleiomyoma being a type of true smooth muscle gastrointestinal tumors can lead to serious life-threatening gastrointestinal bleeding. We report a case of 21-year-old male patient with recurrent midgut bleeding. Contrast-enhanced CT revealed highly vascular small bowel neoplasm. The patient underwent laparotomy with bowel resection and recovered uneventfully. Histopathology revealed jejunal angioleiomyoma. PMID- 27668117 TI - Organ Preservation in a Case of Retroperitoneal Ganglioneuroma: A Case Report and Review of Literature. AB - The retroperitoneum is a closed space harbouring vital organs including the great vessels, kidneys and adrenal glands, ureters, and the ascending and descending colon. Surgical management of retroperitoneal pathologies may need multiorgan resection in order to achieve complete surgical resection while preservation of surrounding organs should be attempted, especially in case of benign tumors. We present a case of 15-year-old girl with an 11 * 6 * 5 cm retroperitoneal ganglioneuroma displacing the right kidney, renal vein, and ureter and abutting the IVC which was excised in toto preserving the right kidney and ureter with careful dissection around the great vessels. We also attempt to review the various surgical options available while dealing with these benign retroperitoneal tumors which are often detected incidentally and usually surround important retroperitoneal organs and vessels. PMID- 27668118 TI - Impact of Body Mass Index on Short-Term Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Newfoundland and Labrador, Canada. AB - Background and Aim. Obesity (BMI >= 30 kg/m(2)) is associated with advanced cardiovascular disease requiring procedures such as percutaneous coronary intervention (PCI). Studies report better outcomes in obese patients having these procedures but results are conflicting or inconsistent. Newfoundland and Labrador (NL) has the highest rate of obesity in Canada. The aim of the study was to examine the relationship between BMI and vascular and nonvascular complications in patients undergoing PCI in NL. Methods. We studied 6473 patients identified in the APPROACH-NL database who underwent PCI from May 2006 to December 2013. BMI categories included normal, 18.5 <= BMI < 25.0 (n = 1073); overweight, 25.0 <= BMI < 30 (n = 2608); and obese, BMI >= 30.0 (n = 2792). Results. Patients with obesity were younger and had a higher incidence of diabetes, hypertension, and family history of cardiac disease. Obese patients experienced less vascular complications (normal, overweight, and obese: 8.2%, 7.2%, and 5.3%, p = 0.001). No significant differences were observed for in-lab (4.0%, 3.3%, and 3.1%, p = 0.386) or postprocedural (1.0%, 0.8%, and 0.9%, p = 0.725) nonvascular complications. After adjusting for covariates, BMI was not a significant factor associated with adverse outcomes. Conclusion. Overweight and obesity were not independent correlates of short-term vascular and nonvascular complications among patients undergoing PCI. PMID- 27668119 TI - Analysis of LRRK2, SNCA, and ITGA8 Gene Variants with Sporadic Parkinson's Disease Susceptibility in Chinese Han Population. AB - Background. Parkinson's disease (PD) is an age-related neurodegenerative disease affected by multiple genetic and environmental factors. We performed a case control study on candidate gene to scrutinize whether genetic variants in LRRK2, SNCA, and ITGA8 genes could be associated with sporadic PD in Chinese Han population. Methods. Five single-nucleotide polymorphisms (SNPs) of LRRK2 (rs1491942), SNCA (rs2301134, rs2301135, and rs356221), and ITGA8 (rs7077361) were selected and genotyped among 583 unrelated PD patients and 558 healthy controls. Results. Rs1491942 of LRRK2 gene had a significantly higher genotype frequency (P = 3.543E - 09) and allelic G/C frequencies (P = 2.601E - 10) in PD patients than controls. Rs2301135 of SNCA gene also showed an obvious difference in genotype frequency (P = 4.394E - 07) and allelic G/C frequencies (P = 9.116E - 13) between PD patients and controls. SNPs rs2301134 and rs356221 of SNCA gene and rs7077361 of ITGA8 gene lacked the significant association with the susceptibility of PD in Chinese Han population. Conclusions. Our study firstly expresses that rs1491942 of LRRK2 and rs2301135 of SNCA gene are substantially associated with sporadic Parkinson's disease in Chinese Han population. PMID- 27668120 TI - Systematic Review of Hospital Readmissions in Stroke Patients. AB - Background. Previous evidence on factors and causes of readmissions associated with high-impact users of stroke is scanty. The aim of the study was to investigate common causes and pattern of short- and long-term readmissions stroke patients by conducting a systematic review of studies using hospital administrative data. Common risk factors associated with the change of readmission rate were also examined. Methods. The literature search was conducted from 15 February to 15 March 2016 using various databases, such as Medline, Embase, and Web of Science. Results. There were a total of 24 studies (n = 2,126,617) included in the review. Only 4 studies assessed causes of readmissions in stroke patients with the follow-up duration from 30 days to 5 years. Common causes of readmissions in majority of the studies were recurrent stroke, infections, and cardiac conditions. Common patient-related risk factors associated with increased readmission rate were age and history of coronary heart disease, heart failure, renal disease, respiratory disease, peripheral arterial disease, and diabetes. Among stroke-related factors, length of stay of index stroke admission was associated with increased readmission rate, followed by bowel incontinence, feeding tube, and urinary catheter. Conclusion. Although risk factors and common causes of readmission were identified, none of the previous studies investigated causes and their sequence of readmissions among high-impact stroke users. PMID- 27668121 TI - Ripening-Dependent Changes in Antioxidants, Color Attributes, and Antioxidant Activity of Seven Tomato (Solanum lycopersicum L.) Cultivars. AB - To evaluate the ripening-dependent changes in phytonutrients, seven commercial cultivars (two general and five cherry) of tomatoes were cultivated under greenhouse conditions. Fruits were harvested at breaker, turning, pink, light red, and red stages of each cultivar, and antioxidant contents, color attributes, and antioxidant activities were measured. During ripening process, lycopene content increased from the breaker to red stage, while lutein displayed the reverse accumulation pattern, with higher values during the breaker stage. In contrast, beta-carotene showed the highest levels of synthesis in pink and light red stages. Furthermore, flavonoids (quercetin, rutin, naringenin, and luteolin) also showed similar ripening-dependent changes, with higher quantities in pink and light red stages. Ascorbic acid showed continuously increasing patterns throughout ripening until the red stage, while the accumulation of total phenolics was cultivar-dependent. These results indicate that each antioxidant compound has a unique pattern of accumulation and degradation during the ripening process. "Unicon" exhibited highest total carotenoid (110.27 mg/100 g), total phenol (297.88 mg GAE/100 g) and total flavonoid content (273.33 mg/100 g), and consequently highest antioxidant activity (2552.4 MUmol TE/100 g) compared to other cultivars. Throughout the ripening processes, total phenolics showed the highest correlation with antioxidant activity, followed by beta-carotene and total flavonoids. In conclusion, ripening in tomatoes is accompanied by incremental increases in various antioxidant compounds to some extent, as well as by concomitant increases in antioxidant activity. PMID- 27668122 TI - Capitalizing Resolving Power of Density Gradient Ultracentrifugation by Freezing and Precisely Slicing Centrifuged Solution: Enabling Identification of Complex Proteins from Mitochondria by Matrix Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry. AB - Density gradient centrifugation is widely utilized for various high purity sample preparations, and density gradient ultracentrifugation (DGU) is often used for more resolution-demanding purification of organelles and protein complexes. Accurately locating different isopycnic layers and precisely extracting solutions from these layers play a critical role in achieving high-resolution DGU separations. In this technique note, we develop a DGU procedure by freezing the solution rapidly (but gently) after centrifugation to fix the resolved layers and by slicing the frozen solution to fractionate the sample. Because the thickness of each slice can be controlled to be as thin as 10 micrometers, we retain virtually all the resolution produced by DGU. To demonstrate the effectiveness of this method, we fractionate complex V from HeLa mitochondria using a conventional technique and this freezing-slicing (F-S) method. The comparison indicates that our F-S method can reduce complex V layer thicknesses by ~40%. After fractionation, we analyze complex V proteins directly on a matrix assisted laser desorption/ionization, time-of-flight mass spectrometer. Twelve out of fifteen subunits of complex V are positively identified. Our method provides a practical protocol to identify proteins from complexes, which is useful to investigate biomolecular complexes and pathways in various conditions and cell types. PMID- 27668123 TI - 24-Hour ICH Score Is a Better Predictor of Outcome than Admission ICH Score. AB - BACKGROUND: The ICH score is a validated tool for predicting 30-day morbidity and mortality in patients with intracerebral hemorrhage. AIMS AND/OR HYPOTHESIS: The aim of this study is to determine if the ICH score calculated 24 hours after admission is a better predictor of mortality than the ICH score calculated on admission. METHODS: Patients presenting to our center with ICH from 7/08-12/10 were retrospectively identified from our prospective stroke registry. ICH scores were calculated based on initial Glasgow coma scale (GCS) and emergent head computed tomography (CT) on initial presentation and were recalculated after 24 hours. RESULTS: A total of 91 patients out of 121 had complete data for admission and 24-hour ICH score. The ICH score changed in 38% from baseline to 24 hours. After adjusting for age, NIHSS on admission, and glucose, ICH score at 24 hours was a significant, independent predictor of mortality (OR = 2.71, 95% CI 1-19 6.20, and P = 0.018), but ICH score on admission was not (OR = 2.14, 95% CI 0.88 5.24, and P = 0.095). CONCLUSION: Early determination of the ICH score may incorrectly estimate the severity and expected outcome after ICH. Calculations of the ICH score 24 hours after admission will better predict early outcomes. PMID- 27668124 TI - Climate Migration and Moral Responsibility. AB - Even though anthropogenic climate change is largely caused by industrialized nations, its burden is distributed unevenly with poor developing countries suffering the most. A common response to livelihood insecurities and destruction is migration. Using Peter Singer's "historical principle" this paper argues that a morally just evaluation requires taking causality between climate change and migration under consideration. The historical principle is employed to emphasize shortcomings in commonly made philosophical arguments to oppose immigration. The article concludes that none of these arguments is able to override the moral responsibility of industrialized countries to compensate for harms that their actions have caused. PMID- 27668125 TI - Role of the Three-Phase Boundary of the Platinum-Support Interface in Catalysis: A Model Catalyst Kinetic Study. AB - A series of microstructured, supported platinum (Pt) catalyst films (supported on single-crystal yttria-stabilized zirconia) and an appropriate Pt catalyst reference system (supported on single-crystal alumina) were fabricated using pulsed laser deposition and ion-beam etching. The thin films exhibit area specific lengths of the three-phase boundary (length of three-phase boundary between the Pt, support, and gas phase divided by the superficial area of the sample) that vary over 4 orders of magnitude from 4.5 * 102 to 4.9 * 106 m m-2, equivalent to structural length scales of 0.2 MUm to approximately 9000 MUm. The catalyst films have been characterized using X-ray diffraction, atomic force microscopy, high-resolution scanning electron microscopy, and catalytic activity tests employing the carbon monoxide oxidation reaction. When Pt is supported on yttria-stabilized zirconia, the reaction rate clearly depends upon the area specific length of the three-phase boundary, l(tpb). A similar relationship is not observed when Pt is supported on alumina. We suggest that the presence of the three-phase boundary provides an extra channel of oxygen supply to the Pt through diffusion in or on the yttria-stabilized zirconia support coupled with surface diffusion across the Pt. PMID- 27668126 TI - Mechanical Designs for Inorganic Stretchable Circuits in Soft Electronics. AB - Mechanical concepts and designs in inorganic circuits for different levels of stretchability are reviewed in this paper, through discussions of the underlying mechanics and material theories, fabrication procedures for the constituent microscale/nanoscale devices, and experimental characterization. All of the designs reported here adopt heterogeneous structures of rigid and brittle inorganic materials on soft and elastic elastomeric substrates, with mechanical design layouts that isolate large deformations to the elastomer, thereby avoiding potentially destructive plastic strains in the brittle materials. The overall stiffnesses of the electronics, their stretchability, and curvilinear shapes can be designed to match the mechanical properties of biological tissues. The result is a class of soft stretchable electronic systems that are compatible with traditional high-performance inorganic semiconductor technologies. These systems afford promising options for applications in portable biomedical and health monitoring devices. Mechanics theories and modeling play a key role in understanding the underlining physics and optimization of these systems. PMID- 27668127 TI - Near-peer STEM Mentoring Offers Unexpected Benefits for Mentors from Traditionally Underrepresented Backgrounds. PMID- 27668128 TI - Health Risks to Ecological Workers on Contaminated Sites - the Department of Energy as a Case Study. AB - BACKGROUND: At most contaminated sites the risk to workers focuses on those 'hazardous waste workers' directly exposed to chemicals or radionuclides, and to the elaborate approaches implemented to protecting their health and safety. Ecological workers generally are not considered. OBJECTIVES: To explore the risks to the health and safety of ecological workers on sites with potential chemical and radiological exposures before, during or after remediation of contamination. To use the U.S. Department of Energy as a case study, and to develop concepts that apply generally to sites contaminated with hazardous or nuclear wastes. METHODS: Develop categories of ecological workers, describe their usual jobs, and provide information on the kinds of risks they face. Ecological activities include continued surveillance and monitoring work on any sites with residual contamination, subject to institutional controls and engineered barriers following closure as well as the restoration. RESULTS: The categories of ecological workers and their tasks include 1) Ecological characterization, mapping and monitoring, 2) biodiversity studies, 2) Contaminant fate and transport, 3) On-going industrial activities 4) Remediation activities (environmental management), 5) Environmental restoration, 6) Post-cleanup surveillance and monitoring, and 7) Post-closure future site activities. There are a set of functional activities that can occur with different frequencies and intensities, including visual inspection, collecting biological samples, collecting media physical samples, collecting biological debris, restoration planting, and maintaining ecosystems. CONCLUSIONS: Ecological workers face different exposures and risks than other environmental cleanup workers. Many of their tasks mimic shift work with long hours leading to fatigue, and they are exposed to biological as well as chemical/radiological hazards. DOE and other entities need to examine the risks to ecological workers on site with an eye to risk reduction. PMID- 27668129 TI - Steroid-Loaded Hemostatic Nanoparticles Combat Lung Injury after Blast Trauma. AB - In response to the lack of therapeutics for internal bleeding following a traumatic event, we synthesized hemostatic dexamethasone nanoparticles (hDNP) to help alleviate internal hemorrhaging. hDNP consist of a block copolymer, poly(lactic-co-glycolic acid)-poly(l-lysine)-poly(ethylene glycol) conjugated to a peptide, glycine-arginine-glycine-aspartic acid-serine (GRGDS). These particles were evaluated as treatment for primary blast lung injury in a rodent model. Animals were randomly placed into test and control groups, exposed to blast and given immediate injection. Recovery was assessed using physiological parameters and immunohistochemistry. We found that dexamethasone-loaded hemostatic nanoparticles alleviate physiological deprivation caused by blast injury and reduce lung injury damage. PMID- 27668131 TI - Safety and Treatment Effectiveness of a Single Autologous Protein Solution Injection in Patients with Knee Osteoarthritis. AB - Osteoarthritis (OA) is a common degenerative condition characterized by pain and loss of function. A pathological biochemical environment with excess inflammatory and catabolic proteins is a major contributor to OA. nSTRIDE((r)) Autologous Protein Solution (APS) is a new therapy under development for the treatment of OA. This therapy is formed from a patient's blood and contains high concentrations of anti-inflammatory and anabolic proteins. This study assessed the safety and treatment effects of APS. Eleven subjects with early to moderate OA were injected with APS. Subjects were closely monitored for adverse events (AE) following the injection. Treatment outcome measures were obtained before injection. AE and clinical outcomes were assessed at 1 and 2 weeks postinjection and 1, 3, and 6 months postinjection. There were no serious AE or AE that were reported by the investigator as greater than mild in severity. There were no AE that were related to the device. There were minor AE related to the injection procedure, including injection site discomfort (1/11), injection site joint pain (1/11), and procedural nausea (1/11), which resolved quickly and did not require treatment. Mean Western Ontario and McMaster Universities Arthritis Index (WOMAC) composite scores and pain, stiffness, and function subscale scores all showed significant improvement compared to baseline by 2 weeks postinjection. The data presented here suggest that the treatment is safe and show a complication profile that is mild and consistent with similar treatments. A single injection of APS for treatment of early to moderate knee OA led to symptom improvement over the study course. Based on these results, an adequately powered, well-controlled, randomized multicenter study to establish clinical efficacy is warranted. PMID- 27668130 TI - The Accuracy and Reliability of Crowdsource Annotations of Digital Retinal Images. AB - PURPOSE: Crowdsourcing is based on outsourcing computationally intensive tasks to numerous individuals in the online community who have no formal training. Our aim was to develop a novel online tool designed to facilitate large-scale annotation of digital retinal images, and to assess the accuracy of crowdsource grading using this tool, comparing it to expert classification. METHODS: We used 100 retinal fundus photograph images with predetermined disease criteria selected by two experts from a large cohort study. The Amazon Mechanical Turk Web platform was used to drive traffic to our site so anonymous workers could perform a classification and annotation task of the fundus photographs in our dataset after a short training exercise. Three groups were assessed: masters only, nonmasters only and nonmasters with compulsory training. We calculated the sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) plots for all classifications compared to expert grading, and used the Dice coefficient and consensus threshold to assess annotation accuracy. RESULTS: In total, we received 5389 annotations for 84 images (excluding 16 training images) in 2 weeks. A specificity and sensitivity of 71% (95% confidence interval [CI], 69%-74%) and 87% (95% CI, 86%-88%) was achieved for all classifications. The AUC in this study for all classifications combined was 0.93 (95% CI, 0.91-0.96). For image annotation, a maximal Dice coefficient (~0.6) was achieved with a consensus threshold of 0.25. CONCLUSIONS: This study supports the hypothesis that annotation of abnormalities in retinal images by ophthalmologically naive individuals is comparable to expert annotation. The highest AUC and agreement with expert annotation was achieved in the nonmasters with compulsory training group. TRANSLATIONAL RELEVANCE: The use of crowdsourcing as a technique for retinal image analysis may be comparable to expert graders and has the potential to deliver timely, accurate, and cost-effective image analysis. PMID- 27668132 TI - Novel Mechanistic Interplay between Products of Oxidative Stress and Components of the Complement System in AMD Pathogenesis. AB - Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD includes soft drusen and pigmentary changes in the retinal pigment epithelium (RPE). As people age, such soft confluent drusen can progress into two forms of advanced AMD, geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD) and result in the loss of central vision. The exact mechanism for developing early AMD and progressing to advanced stage of disease is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as the cause of AMD progression. Together, complement factor H (CFH) and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress from activities such as smoking has also demonstrated a powerful contribution to AMD progression. To extend our previous finding that genetic polymorphisms in CFH results in OxPLs and the risk-form of CFH (CFH Y402H) has reduced affinity for oxidized phospholipids, and subsequent diminished capacity which subsequently diminishes the capability to attenuate the inflammatory effects of these molecules, we compared the binding properties of CFH and CFH related protein 1 (CFHR1), which is also associated with disease risk, to OxPLs and their effects on modulating inflammation and lipids uptake. As both CFH-402H and CFHR1 are associated with increased risk to AMD, we hypothesized that like CFH-402H, CFHR1 contribution to AMD risk may also be due to its diminished affinity for OxPLs. Interestingly, we found that association of CFHR1 with OxPLs was not statistically different than CFH. However, binding of CFHR1 did not elicit the same protective benefits as CFH in that both inflammation and lipid uptake are unaffected by CFHR1 association with OxPLs. These findings demonstrate a novel and interesting complexity to the potential interplay between the complement system and oxidative stress byproducts, such as OxPLs, in the mechanistic contribution to AMD. Future work will aim to identify the molecular distinctions between CFH and CFHR1 which confer protection by the former, but not latter molecules. Understanding the molecular domains necessary for protection could provide interventional insights in the generation of novel therapeutics for AMD and other diseases associated with oxidative stress. PMID- 27668133 TI - Experiences with the Streptococcus Mutans in Lakota Sioux (SMILeS) Study: Risk factors for Caries in American Indian Children 0-3 Years. AB - Severe Early Childhood Caries (S-ECC) is a terribly aggressive and devastating disease that is all too common in lower socio-economic children, but none more so that what is encountered in American Indian Tribes. Nationwide, approximately 27% of 2-5 year olds have decay while 62% percent of American Indian/Alaska Native children in the same age group have a history of decay (IHS 2010, NHANES 1999 2002). We have conducted a study of children from birth to 36 months of age on Pine Reservation to gain a better understanding of the variables that come into play in the development of this disease, from transmission and acquisition of Streptococcus mutans genotypes from mother to child to multiple dietary and behavioral components. This article describes how we established a direct partnership with the Tribe and the many opportunities and challenges we faced in performing this 5-year field study. PMID- 27668134 TI - Sex Disparities in Access to Acute Stroke Care: Can Telemedicine Mitigate this Effect? AB - BACKGROUND: Women have more frequent and severe ischemic strokes than men, and are less likely to receive treatment for acute stroke. Primary stroke centers (PSCs) have been shown to utilize treatment more frequently. Further, as telemedicine (TM) has expanded access to acute stroke care we sought to investigate the association between PSC, TM and access to acute stroke care in the state of Texas. METHODS: Texas hospitals and resources were identified from the 2009 American Hospital Association Annual Survey. Hospitals were categorized as: (1) stand-alone PSCs not using telemedicine for acute stroke care, (2) PSCs using telemedicine for acute stroke care (PSC-TM), (3) non-PSC hospitals using telemedicine for acute stroke care, or (4) non-PSC hospitals not using telemedicine for acute stroke care. The proportion of the population who could reach a PSC within 60 minutes was determined for stand-alone PSCs, PSC-TM, and non-PSCs using TM for stroke care. RESULTS: Overall, women were as likely to have 60-minute access to a PSC or PSC-TM as their male counterparts (POR 1.02, 95% CI 1.02-1.03). Women were also just as likely to have access to acute stroke care via PSC or PSC-TM or TM as men (POR 1.03, 95% CI 1.02-1.04). DISCUSSION: Our study found no sex disparities in access to stand alone PSCs or to hospitals using TM in the state of Texas. The results of this study suggest that telemedicine can be used as part of an inclusive strategy to improve access to care equally for men and women. PMID- 27668136 TI - Characterization and Comparison of Fast Pyrolysis Bio-oils from Pinewood, Rapeseed Cake, and Wheat Straw Using 13C NMR and Comprehensive GC * GC. AB - Fast pyrolysis bio-oils are feasible energy carriers and a potential source of chemicals. Detailed characterization of bio-oils is essential to further develop its potential use. In this study, quantitative 13C nuclear magnetic resonance (13C NMR) combined with comprehensive two-dimensional gas chromatography (GC * GC) was used to characterize fast pyrolysis bio-oils originated from pinewood, wheat straw, and rapeseed cake. The combination of both techniques provided new information on the chemical composition of bio-oils for further upgrading. 13C NMR analysis indicated that pinewood-based bio-oil contained mostly methoxy/hydroxyl (~30%) and carbohydrate (~27%) carbons; wheat straw bio-oil showed to have high amount of alkyl (~35%) and aromatic (~30%) carbons, while rapeseed cake-based bio-oil had great portions of alkyl carbons (~82%). More than 200 compounds were identified and quantified using GC * GC coupled to a flame ionization detector (FID) and a time of flight mass spectrometer (TOF-MS). Nonaromatics were the most abundant and comprised about 50% of the total mass of compounds identified and quantified via GC * GC. In addition, this analytical approach allowed the quantification of high value-added phenolic compounds, as well as of low molecular weight carboxylic acids and aldehydes, which exacerbate the unstable and corrosive character of the bio-oil. PMID- 27668137 TI - Chesapeake Bay nitrogen fluxes derived from a land-estuarine ocean biogeochemical modeling system: Model description, evaluation, and nitrogen budgets. AB - The Chesapeake Bay plays an important role in transforming riverine nutrients before they are exported to the adjacent continental shelf. Although the mean nitrogen budget of the Chesapeake Bay has been previously estimated from observations, uncertainties associated with interannually varying hydrological conditions remain. In this study, a land-estuarine-ocean biogeochemical modeling system is developed to quantify Chesapeake riverine nitrogen inputs, within estuary nitrogen transformation processes and the ultimate export of nitrogen to the coastal ocean. Model skill was evaluated using extensive in situ and satellite-derived data, and a simulation using environmental conditions for 2001 2005 was conducted to quantify the Chesapeake Bay nitrogen budget. The 5 year simulation was characterized by large riverine inputs of nitrogen (154 * 109 g N yr-1) split roughly 60:40 between inorganic:organic components. Much of this was denitrified (34 * 109 g N yr-1) and buried (46 * 109 g N yr-1) within the estuarine system. A positive net annual ecosystem production for the bay further contributed to a large advective export of organic nitrogen to the shelf (91 * 109 g N yr-1) and negligible inorganic nitrogen export. Interannual variability was strong, particularly for the riverine nitrogen fluxes. In years with higher than average riverine nitrogen inputs, most of this excess nitrogen (50-60%) was exported from the bay as organic nitrogen, with the remaining split between burial, denitrification, and inorganic export to the coastal ocean. In comparison to previous simulations using generic shelf biogeochemical model formulations inside the estuary, the estuarine biogeochemical model described here produced more realistic and significantly greater exports of organic nitrogen and lower exports of inorganic nitrogen to the shelf. PMID- 27668135 TI - Recombinant adeno-associated virus vectors in the treatment of rare diseases. AB - INTRODUCTION: An estimated 25 million Americans are living with rare diseases. Adeno-associated virus (AAV)-mediated gene therapy is an emerging therapeutic option for the more than 7,000 identified rare diseases. This paper highlights the benefits of AAV therapy compared to conventional small molecules, discusses current pre-clinical and clinical applications of AAV-mediated gene therapy, and offers insights into cutting edge research that will shape the future of AAV for broad therapeutic use. AREAS COVERED: In this review the biology of AAV and our ability to generate disease-specific variants is summarized. Limitations of current therapy are reviewed, with an emphasis on immune detection of virus, viral tropism and tissue targeting, and limitations of gene expression. Information for this review was found using PubMed and clinicaltrials.gov. EXPERT OPINION: Currently the scope of clinical trials of AAV gene therapy is concentrated in an array of phase I/II safety trials with less than two dozen rare diseases featured. Pre-clinical, translational studies are expanding in number as developments within the last decade have made generation of improved AAV vectors available to more researchers. Further, one bottleneck that is being overcome is the availability of disease models, which will allow for improved preclinical testing and advancement of AAV to more clinical applications. PMID- 27668138 TI - Silicon chemistry in the mesosphere and lower thermosphere. AB - Silicon is one of the most abundant elements in cosmic dust, and meteoric ablation injects a significant amount of Si into the atmosphere above 80 km. In this study, a new model for silicon chemistry in the mesosphere/lower thermosphere is described, based on recent laboratory kinetic studies of Si, SiO, SiO2, and Si+. Electronic structure calculations and statistical rate theory are used to show that the likely fate of SiO2 is a two-step hydration to silicic acid (Si(OH)4), which then polymerizes with metal oxides and hydroxides to form meteoric smoke particles. This chemistry is then incorporated into a whole atmosphere chemistry-climate model. The vertical profiles of Si+ and the Si+/Fe+ ratio are shown to be in good agreement with rocket-borne mass spectrometric measurements between 90 and 110 km. Si+ has consistently been observed to be the major meteoric ion around 110 km; this implies that the relative injection rate of Si from meteoric ablation, compared to metals such as Fe and Mg, is significantly larger than expected based on their relative chondritic abundances. Finally, the global abundances of SiO and Si(OH)4 show clear evidence of the seasonal meteoric input function, which is much less pronounced in the case of other meteoric species. PMID- 27668140 TI - MIDAS robust trend estimator for accurate GPS station velocities without step detection. AB - Automatic estimation of velocities from GPS coordinate time series is becoming required to cope with the exponentially increasing flood of available data, but problems detectable to the human eye are often overlooked. This motivates us to find an automatic and accurate estimator of trend that is resistant to common problems such as step discontinuities, outliers, seasonality, skewness, and heteroscedasticity. Developed here, Median Interannual Difference Adjusted for Skewness (MIDAS) is a variant of the Theil-Sen median trend estimator, for which the ordinary version is the median of slopes vij = (xj-xi )/(tj-ti ) computed between all data pairs i > j. For normally distributed data, Theil-Sen and least squares trend estimates are statistically identical, but unlike least squares, Theil-Sen is resistant to undetected data problems. To mitigate both seasonality and step discontinuities, MIDAS selects data pairs separated by 1 year. This condition is relaxed for time series with gaps so that all data are used. Slopes from data pairs spanning a step function produce one-sided outliers that can bias the median. To reduce bias, MIDAS removes outliers and recomputes the median. MIDAS also computes a robust and realistic estimate of trend uncertainty. Statistical tests using GPS data in the rigid North American plate interior show +/-0.23 mm/yr root-mean-square (RMS) accuracy in horizontal velocity. In blind tests using synthetic data, MIDAS velocities have an RMS accuracy of +/-0.33 mm/yr horizontal, +/-1.1 mm/yr up, with a 5th percentile range smaller than all 20 automatic estimators tested. Considering its general nature, MIDAS has the potential for broader application in the geosciences. PMID- 27668139 TI - An assessment of phytoplankton primary productivity in the Arctic Ocean from satellite ocean color/in situ chlorophyll-a based models. AB - We investigated 32 net primary productivity (NPP) models by assessing skills to reproduce integrated NPP in the Arctic Ocean. The models were provided with two sources each of surface chlorophyll-a concentration (chlorophyll), photosynthetically available radiation (PAR), sea surface temperature (SST), and mixed-layer depth (MLD). The models were most sensitive to uncertainties in surface chlorophyll, generally performing better with in situ chlorophyll than with satellite-derived values. They were much less sensitive to uncertainties in PAR, SST, and MLD, possibly due to relatively narrow ranges of input data and/or relatively little difference between input data sources. Regardless of type or complexity, most of the models were not able to fully reproduce the variability of in situ NPP, whereas some of them exhibited almost no bias (i.e., reproduced the mean of in situ NPP). The models performed relatively well in low productivity seasons as well as in sea ice-covered/deep-water regions. Depth resolved models correlated more with in situ NPP than other model types, but had a greater tendency to overestimate mean NPP whereas absorption-based models exhibited the lowest bias associated with weaker correlation. The models performed better when a subsurface chlorophyll-a maximum (SCM) was absent. As a group, the models overestimated mean NPP, however this was partly offset by some models underestimating NPP when a SCM was present. Our study suggests that NPP models need to be carefully tuned for the Arctic Ocean because most of the models performing relatively well were those that used Arctic-relevant parameters. PMID- 27668142 TI - Global MHD modeling of resonant ULF waves: Simulations with and without a plasmasphere. AB - We investigate the plasmaspheric influence on the resonant mode coupling of magnetospheric ultralow frequency (ULF) waves using the Lyon-Fedder-Mobarry (LFM) global magnetohydrodynamic (MHD) model. We present results from two different versions of the model, both driven by the same solar wind conditions: one version that contains a plasmasphere (the LFM coupled to the Rice Convection Model, where the Gallagher plasmasphere model is also included) and another that does not (the stand-alone LFM). We find that the inclusion of a cold, dense plasmasphere has a significant impact on the nature of the simulated ULF waves. For example, the inclusion of a plasmasphere leads to a deeper (more earthward) penetration of the compressional (azimuthal) electric field fluctuations, due to a shift in the location of the wave turning points. Consequently, the locations where the compressional electric field oscillations resonantly couple their energy into local toroidal mode field line resonances also shift earthward. We also find, in both simulations, that higher-frequency compressional (azimuthal) electric field oscillations penetrate deeper than lower frequency oscillations. In addition, the compressional wave mode structure in the simulations is consistent with a radial standing wave oscillation pattern, characteristic of a resonant waveguide. The incorporation of a plasmasphere into the LFM global MHD model represents an advance in the state of the art in regard to ULF wave modeling with such simulations. We offer a brief discussion of the implications for radiation belt modeling techniques that use the electric and magnetic field outputs from global MHD simulations to drive particle dynamics. PMID- 27668141 TI - High correlations between temperature and nitric oxide in the thermosphere. AB - Obtaining accurate predictions of the neutral density in the thermosphere has been a long-standing problem. During geomagnetic storms the auroral heating in the polar ionospheres quickly raises the temperature of the thermosphere, resulting in higher neutral densities that exert a greater drag force on objects in low Earth orbit. Rapid increases and decreases in the temperature and density may occur within a couple days. A key parameter in the thermosphere is the total amount of nitric oxide (NO). The production of NO is accelerated by the auroral heating, and since NO is an efficient radiator of thermal energy, higher concentrations of this molecule accelerate the rate at which the thermosphere cools. This paper describes an improved technique that calculates changes in the global temperature of the thermosphere. Starting from an empirical model of the Poynting flux into the ionosphere, a set of differential equations derives the minimum, global value of the exospheric temperature, which can be used in a neutral density model to calculate the global values. The relative variations in NO content are used to obtain more accurate cooling rates. Comparisons with the global rate of NO emissions that are measured with the Sounding of the Atmosphere using Broadband Emission Radiometry instrument show that there is very good agreement with the predicted values. The NO emissions correlate highly with the total auroral heating that has been integrated over time. We also show that the NO emissions are highly correlated with thermospheric temperature, as well as indices of solar extreme ultraviolet radiation. PMID- 27668143 TI - An NO/GSNO-based Neuroregeneration Strategy for Stroke Therapy. AB - Stroke is associated with significant morbidity and mortality due to the limited neuroregeneration capacity of the injured brain. Other than thrombolysis in the acute phase of the disease by tissue plasminogen activator (tPA), which offers only a short window of treatment (~3 hours), an ideal stroke therapy is not available mainly because of limited understanding of the mechanisms of neuroregeneration and functional recovery in the chronic phase. Yet many drug therapies, including S-nitrosoglutathione (GSNO), have been shown to provide neuroprotection against acute disease in animal models of transient cerebral ischemia reperfusion (IR) and permanent ischemia. GSNO was also effective in stimulating neuroregeneration-related factors in the chronic phase of the disease. In this short review, we assess the evidence supporting exogenous administration of GSNO after experimental stroke as a means to stimulate neuroregeneration and aid in functional recovery via stabilization of the HIF 1alpha/VEGF pathway. PMID- 27668144 TI - Lean NAFLD: An Underrecognized Outlier. AB - Nonalcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese or overweight individuals. However, lean individuals with NAFLD are not rare but represent one significant end of the phenotypic spectrum of NAFLD. Although initial observations between obese and lean NAFLD reveal some metabolic parallels, these associations vary widely given differences in study populations and metabolic parameters assessed. The role of body composition in risk assessment is significant and incompletely assessed during most clinical encounters. Recent multinational investigation reveals an increased mortality in lean individuals with NASH. Many aspects of lean NAFLD need further exploration including epidemiology, clinical risk assessment, histologic changes unique to lean NAFLD, genetic and pathophysiologic mechanisms predisposing at risk individuals, natural history and treatment strategies in this underrecognized population. PMID- 27668145 TI - A Re-evaluation of Electron-Transfer Mechanisms in Microbial Electrochemistry: Shewanella Releases Iron that Mediates Extracellular Electron Transfer. AB - Exoelectrogenic bacteria can couple their metabolism to extracellular electron acceptors, including macroscopic electrodes, and this has applications in energy production, bioremediation and biosensing. Optimisation of these technologies relies on a detailed molecular understanding of extracellular electron-transfer (EET) mechanisms, and Shewanella oneidensis MR-1 (MR-1) has become a model organism for such fundamental studies. Here, cyclic voltammetry was used to determine the relationship between the surface chemistry of electrodes (modified gold, ITO and carbon electrodes) and the EET mechanism. On ultra-smooth gold electrodes modified with self-assembled monolayers containing carboxylic-acid terminated thiols, an EET pathway dominates with an oxidative catalytic onset at 0.1 V versus SHE. Addition of iron(II)chloride enhances the catalytic current, whereas the siderophore deferoxamine abolishes this signal, leading us to conclude that this pathway proceeds via an iron mediated electron transfer mechanism. The same EET pathway is observed at other electrodes, but the onset potential is dependent on the electrolyte composition and electrode surface chemistry. EET pathways with onset potentials above -0.1 V versus SHE have previously been ascribed to direct electron-transfer (DET) mechanisms through the surface exposed decaheme cytochromes (MtrC/OmcA) of MR-1. In light of the results reported here, we propose that the previously identified DET mechanism of MR-1 needs to be re-evaluated. PMID- 27668146 TI - Relationship Between Accelerometer-Measured Activity and Self-Reported or Performance-Based Function in Older Adults with Severe Aortic Stenosis. AB - In older adults with aortic stenosis, we evaluated whether accelerometer-measured physical activity provides distinct clinical information apart from self-reported surveys or performance-based function tests. We employed wrist-mounted accelerometry in 52 subjects with severe aortic stenosis prior to transcatheter aortic valve replacement (TAVR). Daily daytime activity was estimated using the maximum 10 h of daily accelerometer-measured activity (M10) reported in activity counts. Subjects completed baseline surveys (New York Heart Association (NYHA), Short Form 12 (SF12), Kansas City Cardiomyopathy Questionnaire (KCCQ), EuroQol-5D (EQ-5D), Revised Life Orientation Test (LOT-R), Life Space, Detailed Activity Form) and performance-based function tests (Short Physical Performance Battery, 6 min walk test distance, grip strength) to estimate functional status. Simple and multiple linear regression models were used to evaluate the relationship between accelerometer-measured activity and survey data and performance-based function tests. Among all baseline surveys and performance-based function tests, the only statistically significant univariable relationships identified were weak, negative associations between M10 and SF-12 Mental Composite Score (R2=0.1970, P=0.04) and between M10 and grip strength (R2=0.1568, P=0.004). Neither multiple linear regression of overall survey data (R2=0.6159, P=0.23) nor performance based function tests (R2=0.1743, P=0.10) correlated with M10. Self-reported surveys and performance-based function tests are not meaningfully correlated with daytime accelerometer-measured activity. The results of our study suggest that accelerometer-measured physical activity provides distinct clinical information apart from self-reported surveys or performance-based function tests. PMID- 27668148 TI - Regioselective Localization and Tracking of Biomolecules on Single Gold Nanoparticles. AB - Selective localization of biomolecules at the hot spots of a plasmonic nanoparticle is an attractive strategy to exploit the light-matter interaction due to the high field concentration. Current approaches for hot spot targeting are time-consuming and involve prior knowledge of the hot spots. Multiphoton plasmonic lithography is employed to rapidly immobilize bovine serum albumin (BSA) hydrogel at the hot spot tips of a single gold nanotriangle (AuNT). Regioselectivity and quantity control by manipulating the polarization and intensity of the incident laser are also established. Single AuNTs are tracked using dark-field scattering spectroscopy and scanning electron microscopy to characterize the regioselective process. Fluorescence lifetime measurements further confirm BSA immobilization on the AuNTs. Here, the AuNT-BSA hydrogel complexes, in conjunction with single-particle optical monitoring, can act as a framework for understanding light-molecule interactions at the subnanoparticle level and has potential applications in biophotonics, nanomedicine, and life sciences. PMID- 27668147 TI - Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction. AB - Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI. PMID- 27668149 TI - Conjugated Polymer Nanoparticles for Label-Free and Bioconjugate-Recognized DNA Sensing in Serum. AB - Hybridbio/-synthetic sensory conjugated polymer nanoparticles (CPNs) are developed for selective label-free detection of target ssDNA in serum. Carboxylic acid-functionalized anionic polyfluorene nanoparticles are rationally designed as signal amplifying unit to bioconjugate with amine functionalized single stranded oligonucleotides as a receptor. The covalent DNA coating can significantly improve the photostability of the DNA-bioconjugated CPNs over a wide range of buffer conditions. Better ssDNA discrimination for the DNA-bioconjugated CPNs sensor is achieved owing to increased interchain interactions and more efficient exciton transport in nanoparticles. The distinguishable fluorescent color for DNA bioconjugated CPNs in the presence of target ssDNA allows naked-eye detection of ssDNA under UV irradiation. PMID- 27668150 TI - Bio-Inspired Leaf-Mimicking Nanosheet/Nanotube Heterostructure as a Highly Efficient Oxygen Evolution Catalyst. AB - Plant leaves represent a unique 2D/1D heterostructure for enhanced surface reaction and efficient mass transport. Inspired by plant leaves, a 2D/1D CoO x heterostructure is developed that is composed of ultrathin CoO x nanosheets further assembled into a nanotube structure. This bio-inspired architecture allows a highly active Co2+ electronic structure for an efficient oxygen evolution reaction (OER) at the atomic scale, ultrahigh surface area (371 m2 g-1) for interfacial electrochemical reaction at the nanoscale, and enhanced transport of charge and electrolyte over CoO x nanotube building blocks at the microscale. Consequently, this CoO x nanosheet/nanotube heterostructure demonstrates a record high OER performance based on cobalt compounds reported so far, with an onset potential of ~1.46 V versus reversible hydrogen electrode (RHE), a current density of 51.2 mA cm-2 at 1.65 V versus RHE, and a Tafel slope of 75 mV dec-1. Using the CoO x nanosheet/nanotube catalyst and a Pt-mesh, a full water splitting cell with a 1.5-V battery is also demonstrated. PMID- 27668151 TI - Near-Infrared Colloidal Quantum Dots for Efficient and Durable Photoelectrochemical Solar-Driven Hydrogen Production. AB - A new hybrid photoelectrochemical photoanode is developed to generate H2 from water. The anode is composed of a TiO2 mesoporous frame functionalized by colloidal core@shell quantum dots (QDs) followed by CdS and ZnS capping layers. Saturated photocurrent density as high as 11.2 mA cm-2 in a solar-cell-driven photoelectrochemical system using near-infrared QDs is obtained. PMID- 27668152 TI - Photolithography-Compatible Templated Patterning of Functional Organic Materials in Emulsion. AB - A solution-processed patterning of functional organic materials in emulsion is reported. The concept is to absorb microdrops onto predefined locations by hydrophilicity difference. Owing to a universal solvent used, the method can be applied to pattern variety materials on substrates of interest over large size. The figure shows Rhodamine 6G patterned film. PMID- 27668153 TI - Factor analysis of the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version. AB - The Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A; Flessner et al., 2008) measures the degree to which hair pulling in Trichotillomania (TTM) can be described as "automatic" (i.e., done without awareness and unrelated to affective states) and/or "focused" (i.e., done with awareness and to regulate affective states). Despite preliminary evidence in support of the psychometric properties of the MIST-A, emerging research suggests the original factor structure may not optimally capture TTM phenomenology. Using data from a treatment-seeking TTM sample, the current study examined the factor structure of the MIST-A via exploratory factor analysis. The resulting two factor solution suggested the MIST-A consists of a 5-item "awareness of pulling" factor that measures the degree to which pulling is done with awareness and an 8-item "internal-regulated pulling" factor that measures the degree to which pulling is done to regulate internal stimuli (e.g., emotions, cognitions, and urges). Correlational analyses provided preliminary evidence for the validity of these derived factors. Findings from this study challenge the notions of "automatic" and "focused" pulling styles and suggest that researchers should continue to explore TTM subtypes. PMID- 27668154 TI - Open the black box; is urine valuable for screening BK virus-associated nephropathy? PMID- 27668155 TI - Experimental systems to study the origin of the myofibroblast in peritoneal fibrosis. AB - Peritoneal fibrosis is one of the major complications occurring in long-term peritoneal dialysis patients as a result of injury. Peritoneal fibrosis is characterized by submesothelial thickening and fibrosis which is associated with a decline in peritoneal membrane function. The myofibroblast has been identified as the key player involved in the development and progression of peritoneal fibrosis. Activation of the myofibroblast is correlated with expansion of the extracellular matrix and changes in peritoneal membrane integrity. Over the years, epithelial to mesenchymal transition (EMT) has been accepted as the predominant source of the myofibroblast. Peritoneal mesothelial cells have been described to undergo EMT in response to injury. Several animal and in vitro studies support the role of EMT in peritoneal fibrosis; however, emerging evidence from genetic fate-mapping studies has demonstrated that myofibroblasts may be arising from resident fibroblasts and pericytes/perivascular fibroblasts. In this review, we will discuss hypotheses currently surrounding the origin of the myofibroblast and highlight the experimental systems predominantly being used to investigate this. PMID- 27668156 TI - Cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients. AB - BACKGROUND: Cicletanine is an antihypertensive agent with vasorelaxant and diuretic properties. It has been widely used in European countries; however, cicletanine-associated electrolyte disturbances have yet to be defined. We investigated cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients. METHODS: Data from a total of 68 kidney transplant recipients who were treated for hypertension with cicletanine were retrospectively analyzed. Cicletanine-induced hyponatremia and hypokalemia were defined as serum sodium < 135 mmol/L and potassium < 3.5 mmol/L, respectively, after the use of cicletanine. RESULTS: The average patient age was 50 (+/-11) years, and 44 (65%) were male. The daily dose of cicletanine was 171 +/- 46 mg, and the duration of drug use was 215 +/- 514 days. Hyponatremia occurred in 11 patients (16.2%), and hypokalemia occurred in 8 patients (11.8%). Three patients (4.4%) had hyponatremia and hypokalemia simultaneously. The duration of cicletanine administration was significantly longer in patients with hyponatremia than in those without hyponatremia (943 +/- 958 vs. 74 +/- 166 days, P < 0.05). The occurrence of hypokalemia was not affected by either daily dose or duration of drug use. Among 11 patients with hyponatremia, 10 were corrected within 2 weeks after withdrawal of the drug and 1 was spontaneously corrected. Among 8 cases of hypokalemia, 7 were corrected after withdrawal of the drug and 1 was spontaneously corrected. CONCLUSION: We demonstrate that cicletanine may induce hyponatremia or hypokalemia in kidney transplant patients. Hyponatremia is more frequently associated with cicletanine than hypokalemia, and extended use of cicletanine may increase the risk of hyponatremia. PMID- 27668157 TI - Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy. AB - BACKGROUND: Immunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). METHODS: We included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m(2)/mo) or (2) a rise in serum creatinine to an absolute level of >= 1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. RESULTS: A total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. CONCLUSION: The serum IgE level is potentially associated with disease progression and pathogenesis of IgAN. PMID- 27668158 TI - Plasma endocan level and prognosis of immunoglobulin A nephropathy. AB - BACKGROUND: Endocan, previously called endothelial cell-specific molecule-1, is a soluble proteoglycan that is secreted from vascular endothelial cells. Elevated plasma endocan levels were shown to be associated with poor cardiovascular outcomes in patients with chronic kidney disease (CKD). We investigated the clinical relevance of plasma and urine endocan levels in patients with immunoglobulin A nephropathy (IgAN). METHODS: Sixty-four patients with IgAN and 20 healthy controls were enrolled in this study. Plasma and urine endocan levels were measured. Clinical parameters, pathologic grades, and renal outcomes were compared among subgroups with different plasma and urine endocan levels. RESULTS: Both plasma and urine endocan levels were significantly higher in patients with IgAN than in controls. Elevated serum phosphorus and C-reactive protein were independent determinants for plasma endocan, and elevated C-reactive protein was also an independent determinant for urine endocan levels in multivariate analysis. Plasma endocan level was not significantly different across CKD stages, but patients with higher plasma endocan levels showed adverse renal outcome. Urine endocan levels were also elevated in patients with poor renal function. Cox proportional hazard models showed that high plasma endocan was an independent risk factor for CKD progression after adjusting for the well-known predictors of outcome in patients with IgAN. CONCLUSION: This study suggested that plasma endocan might be useful as a prognostic factor in patients with IgAN. PMID- 27668159 TI - Predictive factors of acute kidney injury in patients undergoing rectal surgery. AB - BACKGROUND: Despite major advance in surgical techniques from open surgery to robot-assisted surgery, acute kidney injury (AKI) is still major postoperative complication in rectal surgery. The purpose of this study is to compare the incidence of postoperative AKI according to different surgical techniques and also the risk factors, outcomes of AKI in patients undergoing rectal cancer surgery. METHODS: A retrospective medical chart review was done in a total of 288 patients who received proctectomy because of rectal cancer from 2011 to 2013. RESULTS: The mean patient age was 62 +/- 12 years, and male was 64.2%. Preoperative creatinine was 0.91 +/- 0.18 mg/dL. Open surgery was performed in 9%, and laparoscopy assisted surgery or robot assisted surgery were performed in 54.8% or 36.1% of patients, respectively. AKI developed in 11 patients (3.82%), 2 (18%) of them received acute hemodialysis. Incidence of AKI was not different according to the surgical technique, however, the presence of diabetes, intraoperative shock, and postoperative ileus was associated with the development of AKI. In addition, AKI patients showed significantly longer hospital stay and higher mortality than non-AKI patients. CONCLUSION: Our study demonstrated that despite advances in surgical techniques, incidence of postoperative AKI remains unchanged and also that postoperative AKI is associated with poor outcome. We also found that presence of diabetes, intraoperative shock and postoperative ileus are strongly associated with the development of AKI. More careful attention should be paid on high risk patients for the development of postoperative AKI regardless of surgical techniques. PMID- 27668160 TI - Prevalence of hypothyroidism in patients with chronic kidney disease: a cross sectional study from North India. AB - BACKGROUND: There is an increased prevalence of hypothyroidism in chronic kidney disease (CKD) patients as the glomerular filtration rate falls. However, there is a paucity of Indian data in this respect. METHODS: A cross-sectional analysis was performed based on the database of the information system of a tertiary care hospital in northern India to retrieve results of nephrology CKD outpatients (> 18 years of age) from September 2013 to October 2015 to determine the prevalence of hypothyroidism in the non-dialysis-dependent CKD population. Overt hypothyroidism was defined by a thyroid-stimulating hormone (TSH) level > 5.5 mIU/L and free T4 level < 0.89 ng/dL with clinical symptoms. Subclinical hypothyroidism was defined by a TSH level > 5.5 mIU/L and a free T4 level >= 0.89 ng/dL. RESULTS: Among 1,863 CKD patients, 358 patients underwent biochemical analysis for hypothyroidism. Among these, 143 had biochemical subclinical hypothyroidism and 59 had overt hypothyroidism. Patients in the overt hypothyroid group had significantly higher TSH levels and a lower free T4 level than those in the nonhypothyroid group. Patients with hypothyroidism (both clinical and subclinical) had significantly lower serum albumin and serum calcium levels than those in the nonhypothyroid group. Intact parathyroid hormone was also significantly higher in the hypothyroid groups. An increased prevalence of hypothyroidism was observed in patients with a reduction in the glomerular filtration rate. CONCLUSION: There is growing evidence of increased prevalence of hypothyroidism in dialysis-independent CKD patients. A number of findings such as lower serum albumin, serum calcium, and hemoglobin levels and higher intact parathyroid hormone levels are seen in this group. Specific treatment can help improve these. Hence, there is a need to formulate guidelines to screen this population for hypothyroidism. PMID- 27668161 TI - Low prealbumin levels are independently associated with higher mortality in patients on peritoneal dialysis. AB - BACKGROUND: Prealbumin, a sensitive marker for protein-energy status, is also known as an independent risk factor for mortality in hemodialysis patients. We investigated the impact of prealbumin on survival in incident peritoneal dialysis (PD) patients. METHODS: In total, 136 incident PD patients (mean age, 53.0 +/- 15.8 years) between 2002 and 2007 were enrolled in the study. Laboratory data, dialysis adequacy, and nutritional parameters were assessed 3 months after PD initiation. Patients were classified into 2 groups according to prealbumin level: high prealbumin (>= 40 mg/dL) and low prealbumin (< 40 mg/dL). RESULTS: The patients in the low-prealbumin group were older and had more comorbidities such as diabetes and cardiovascular diseases compared with the patients in the high prealbumin group. Mean subjective global assessment scores were lower, and the high-sensitivity C-reactive protein levels were higher in the low-prealbumin group. Serum creatinine, albumin, and transferrin levels; percent lean body mass; and normalized protein catabolic rate were positively associated, whereas subjective global assessment scores and high-sensitivity C-reactive protein levels were negatively associated with prealbumin concentration. During the median follow-up of 49 months, patients in the lower prealbumin group had a higher mortality rate. Multivariate analysis revealed that prealbumin < 40 mg/dL (hazard ratio, 2.30; 95% confidence interval, 1.14-4.64) was an independent risk factor for mortality. In receiver operating characteristic curves, the area under the curve of prealbumin for mortality was the largest among the parameters. CONCLUSION: Prealbumin levels were an independent and sensitive predictor for mortality in incident PD patients, showing a good correlation with nutritional and inflammatory markers. PMID- 27668162 TI - High-level viruria as a screening tool for BK virus nephropathy in renal transplant recipients. AB - BACKGROUND: Although early monitoring of BK virus infection in renal transplant patients has led to improved outcomes over the past decade, it remains unclear whether monitoring for viremia is the best screening tool for BK virus nephropathy (BKVN). METHODS: We conducted a retrospective review of the medical records of 368 renal transplant recipients who had a minimum of 18 months of posttransplantation follow-up. The relationship between the presence of BK viruria and a composite end point of BK viremia/BKVN was established, and the predictive value of high-grade BK viruria for development of viremia/BKVN was determined. RESULTS: High grade of BK viruria was present in 110 (30.1%) of the renal transplant recipients. BK viremia/BKVN was present in 64 (17.4%) patients and was 50 times more likely to be present in patients with high-grade BK viruria. The risk of developing BK viremia/BKVN was 3 times higher in high-grade viruria patients, and viruria preceded viremia by nearly 7 weeks. CONCLUSION: The presence of high-grade viruria is an early marker for developing BK viremia/BKVN. Detection of high-grade viruria should prompt early allograft biopsy and/or preemptive reduction in immunosuppression. PMID- 27668164 TI - Cardiac arrest caused by nafamostat mesilate. AB - A 65-year-old man was transferred from the Department of Vascular Surgery to Nephrology because of cardiac arrest during hemodialysis. He underwent incision and drainage for treatment of a buttock abscess. Nafamostat mesilate was used as an anticoagulant for hemodialysis to address bleeding from the incision and drainage site. Sudden cardiac arrest occurred after 15 minutes of dialysis. The patient was treated in the intensive care unit for 5 days. Continuous veno-venous hemodiafiltration was started without any anticoagulant in the intensive care unit. Conventional hemodialysis was reinitiated, and nafamostat mesilate was used again because of a small amount of continued bleeding. Ten minutes after hemodialysis, the patient complained of anaphylactic signs and symptoms such as dyspnea, hypotension, and facial swelling. Epinephrine, dexamethasone, and pheniramin were injected under the suspicion of anaphylactic shock, and the patient recovered. Total immunoglobulin E titer was high, and skin prick test revealed weak positivity for nafamostat mesilate. We first report a case of anaphylactic shock caused by nafamostat mesilate in Korea. PMID- 27668165 TI - Henoch-Schonlein purpura nephritis and colitis in an adult patient with alcoholic liver cirrhosis. PMID- 27668163 TI - Rhabdomyolysis in a patient taking nebivolol. AB - beta Blockers such as propranolol and labetalol are known to induce toxic myopathy because of their partial beta2 adrenoceptor agonistic effect. Nebivolol has the highest beta1 receptor affinity among beta blockers, and it has never been reported to induce rhabdomyolysis until now. We report a patient who developed rhabdomyolysis after changing medication to nebivolol. A 75-year-old woman was admitted to our hospital because of generalized weakness originating 2 weeks before visiting. Approximately 1 month before her admission, her medication was changed from carvedilol 12.5 mg to nebivolol 5 mg. Over this time span, she had no other lifestyle changes causing rhabdomyolysis. Her blood chemistry and whole body bone scan indicated rhabdomyolysis. We considered newly prescribed nebivolol as a causal agent. She was prescribed carvedilol 12.5 mg, which she was previously taking, instead of nebivolol. She was treated by hydration and urine alkalization. She had fully recovered and was discharged. PMID- 27668166 TI - The association between acute kidney injury in renal infarction and progression to chronic kidney disease. PMID- 27668167 TI - The authors reply. PMID- 27668168 TI - Omics challenges and unmet translational needs. PMID- 27668169 TI - Standardization and quality management in next-generation sequencing. AB - DNA sequencing continues to evolve quickly even after > 30 years. Many new platforms suddenly appeared and former established systems have vanished in almost the same manner. Since establishment of next-generation sequencing devices, this progress gains momentum due to the continually growing demand for higher throughput, lower costs and better quality of data. In consequence of this rapid development, standardized procedures and data formats as well as comprehensive quality management considerations are still scarce. Here, we listed and summarized current standardization efforts and quality management initiatives from companies, organizations and societies in form of published studies and ongoing projects. These comprise on the one hand quality documentation issues like technical notes, accreditation checklists and guidelines for validation of sequencing workflows. On the other hand, general standard proposals and quality metrics are developed and applied to the sequencing workflow steps with the main focus on upstream processes. Finally, certain standard developments for downstream pipeline data handling, processing and storage are discussed in brief. These standardization approaches represent a first basis for continuing work in order to prospectively implement next-generation sequencing in important areas such as clinical diagnostics, where reliable results and fast processing is crucial. Additionally, these efforts will exert a decisive influence on traceability and reproducibility of sequence data. PMID- 27668170 TI - Metabolic modeling with Big Data and the gut microbiome. AB - The recent advances in high-throughput omics technologies have enabled researchers to explore the intricacies of the human microbiome. On the clinical front, the gut microbial community has been the focus of many biomarker-discovery studies. While the recent deluge of high-throughput data in microbiome research has been vastly informative and groundbreaking, we have yet to capture the full potential of omics-based approaches. Realizing the promise of multi-omics data will require integration of disparate omics data, as well as a biologically relevant, mechanistic framework - or metabolic model - on which to overlay these data. Also, a new paradigm for metabolic model evaluation is necessary. Herein, we outline the need for multi-omics data integration, as well as the accompanying challenges. Furthermore, we present a framework for characterizing the ecology of the gut microbiome based on metabolic network modeling. PMID- 27668171 TI - A systems approach to personalised nutrition: Report on the Keystone Symposium "Human Nutrition, Environment and Health". PMID- 27668172 TI - Barriers to clinical adoption of next generation sequencing: Perspectives of a policy Delphi panel. AB - This research aims to inform policymakers by engaging expert stakeholders to identify, prioritize, and deliberate the most important and tractable policy barriers to the clinical adoption of next generation sequencing (NGS). A 4-round Delphi policy study was done with a multi-stakeholder panel of 48 experts. The first 2 rounds of online questionnaires (reported here) assessed the importance and tractability of 28 potential barriers to clinical adoption of NGS across 3 major policy domains: intellectual property, coverage and reimbursement, and FDA regulation. We found that: 1) proprietary variant databases are seen as a key challenge, and a potentially intractable one; 2) payer policies were seen as a frequent barrier, especially a perceived inconsistency in standards for coverage; 3) relative to other challenges considered, FDA regulation was not strongly perceived as a barrier to clinical use of NGS. Overall the results indicate a perceived need for policies to promote data-sharing, and a desire for consistent payer coverage policies that maintain reasonably high standards of evidence for clinical utility, limit testing to that needed for clinical care decisions, and yet also flexibly allow for clinician discretion to use genomic testing in uncertain circumstances of high medical need. PMID- 27668173 TI - Nasal high flow reduces hypercapnia by clearance of anatomical dead space in a COPD patient. AB - Chronic obstructive pulmonary disease (COPD) with hypercapnia is associated with increased mortality. Non-invasive ventilation (NIV) can lower hypercapnia and ventilator loads but is hampered by a low adherence rate leaving a majority of patients insufficiently treated. Recently, nasal high flow (NHF) has been introduced in the acute setting in adults, too. It is an open nasal cannula system for delivering warm and humidified air or oxygen at high flow rates (2-50 L/min) assisting ventilation. It was shown that this treatment can improve hypercapnia. The mechanism of reducing arterial carbon dioxide (CO2) is proposed through a reduction in nasal dead space ventilation, but there are no studies in which dead space volume was measured in spontaneously breathing subjects. In our case report we measured in a tracheostomized COPD patient CO2 and pressure via sealed ports in the tracheostomy cap and monitored transcutaneous CO2 and tidal volumes. NHF (30 L/min mixed with 3 L/min oxygen) was administered repeatedly at 15-minutes intervals. Inspired CO2 decreased instantly with onset of NHF, followed by a reduction in transcutaneous/arterial CO2. Minute ventilation on nasal high flow was also reduced by 700 ml, indicating that nasal high flow led to a reduction of dead space ventilation thereby improving alveolar ventilation. In conclusion, NHF assist ventilation through clearance of anatomical dead space, which improves alveolar ventilation. Since the reduction in hypercapnia was similar to that reported with effective NIV treatment NHF may become an alternative to NIV in hypercapnic respiratory failure. PMID- 27668174 TI - Focal lung infiltrate complicating PD-1 inhibitor use: A new pattern of drug associated lung toxicity? AB - A 58-year-old woman with stage 4 adenocarcinoma of the lung being treated with pembrolizumab developed dyspnea, non-productive cough, and a right middle lobe infiltrate. Complete resolution of the infiltrate with cessation of pembrolizumab, initiation of prednisone and no antibiotic therapy suggested drug associated lung toxicity as the cause. While the programmed death-1 (PD-1) inhibitors -pembrolizumab and nivolumab - have been implicated as a cause of diffuse or multifocal pulmonary infiltrates, the current case represents, to our knowledge, the first instance of a unilobar, focal infiltrate associated with their use. We speculate that the blockade of immune tolerance that is the hallmark of PD-1 inhibitors might cause atypical inflammatory reactions such as the focal lobar infiltrate seen in the current patient. Awareness of this novel radiographic pattern of drug-associated lung toxicity may enhance clinicians' management of patients receiving. PMID- 27668175 TI - Changes of grey matter volume in first-episode drug-naive adult major depressive disorder patients with different age-onset. AB - OBJECTIVE: Little is known about the pathological mechanism of early adult onset depression (EOD) and later adult onset depression (LOD). We seek to determine whether grey matter volume (GMV) change in EOD and LOD are different, which could also delineate EOD and LOD. METHODS: In present study, 147 first-episode, drug naive patients with major depressive disorder (MDD), age between 18 and 45, were divided into two groups on the basis of age of MDD onset: the early adult onset group (age 18-29) and the later adult onset group (age 30-44), and a total of 130 gender-, and age-, matched healthy controls (HC) were also divided into two groups which fit for each patient group. Magnetic resonance imaging was conducted on all subjects. The voxel-based morphometry (VBM) approach was employed to analyze the images. RESULTS: Widespread abnormalities of GMV throughout parietal, temporal, limbic regions, occipital cortex and cerebellum were observed in MDD patients. Compare to young HC, reduced GMV in right fusiform gyrus, right middle temporal gyrus, vermis III and increased GMV in right middle occipital gyrus were seen in the EOD group. In contrast, relative to old HC, decreased GMV in the right hippocampus and increased GMV in the left middle temporal gyrus were observed in the LOD group. Compared to the LOD group, the EOD group had smaller GMV in right posterior cingulate cortex. There was no significant correlation between GMV of the right posterior cingulate cortex and the score of the depression rating scale in patients group. CONCLUSIONS: The GMV of the brain areas that were related to mood regulation was decreased in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different GMV changes relative to each age-matched comparison group, suggesting depressed adult patients with different age-onset might have different pathological mechanism. PMID- 27668176 TI - Aberrant prefrontal beta oscillations predict episodic memory encoding deficits in schizophrenia. AB - Verbal episodic memory is one of the core cognitive functions affected in patients with schizophrenia (SZ). Although this verbal memory impairment in SZ is a well-known finding, our understanding about its underlying neurophysiological mechanisms is rather scarce. Here we address this issue by recording brain oscillations during a memory task in a sample of healthy controls and patients with SZ. Brain oscillations represent spectral fingerprints of specific neurocognitive operations and are therefore a promising tool to identify neurocognitive mechanisms that are affected by SZ. Healthy controls showed a prominent suppression of left prefrontal beta oscillatory activity during successful memory formation, which replicates several previous oscillatory memory studies. In contrast, patients failed to exhibit such a left prefrontal beta power suppression. Utilizing a new topographical pattern similarity approach, we further demonstrate that the degree of similarity between a patient's beta power decrease to that of the controls reliably predicted memory performance. This relationship between beta power decreases and memory was such that the patients' memory performance improved as they showed a more similar topographical beta desynchronization pattern compared to that of healthy controls. Together, these findings support left prefrontal beta desynchronization as the spectral fingerprint of verbal episodic memory formation, likely indicating deep semantic processing of verbal material. These findings also demonstrate that left prefrontal beta power suppression (or lack thereof) during memory encoding are a reliable biomarker for the observed encoding impairments in SZ in verbal memory. PMID- 27668177 TI - The life cycle of the reptile-inhabiting nematode Abbreviata hastaspicula (Spirurida: Physalopteridae: Physalopterinae) in Australia. AB - This study elucidates the life-cycle of the reptile inhabiting nematode Abbreviata hastaspicula (Spirurida: Physalopteridae: Physalopterinae) in Australia. Eight Varanus gouldii (Lacertilia: Varanidae), and two Christinus marmoratus (Reptilia: Gekkonidae) lizards were captured in the wild. Two V. gouldii were used as controls and no experimental procedures were carried out on them. Another six V. gouldii (final host) and the two C. marmoratus (paratenic host) were treated with oral anthelmintics to remove all parasitic worms and were fed with infected live arthropods containing third stage larvae of Abbreviata hastaspicula. Faeces of V. gouldii were examined under the microscope weekly to determine whether the third stage larvae had developed into adults. Two months later, a total of 30 larvae and adults of A. hastaspicula were found in the stomachs of four experimentally-infected V. gouldii lizards. No cysts or larva were found in the C. marmoratus. This is the first study to demonstrate the life cycle of this genus of nematode in their definitive reptile hosts. PMID- 27668178 TI - Controllable yawning expressed as focal seizures of frontal lobe epilepsy. AB - Excessive yawning was described in some neurological conditions as part of periictal or ictal manifestations of epilepsy, most commonly temporal lobe. We present the first case of controllable yawning as a primary seizure semiology with dominant frontal lobe involvement in a 20-year-old man. Video electroencephalography recorded 8 yawning episodes accompanied with right arm movement correlating with rhythmic diffuse theta range activity with left hemispheric predominance. Magnetoencephalography coherence source imaging was consistent with persistent neuronal networks with areas of high coherence reliably present over the left lateral orbitofrontal region. Epileptogenic areas may have widespread networks involving the dominant frontal lobe in unique symptomatogenic areas. PMID- 27668179 TI - A case of symptomatic reflex epilepsy precipitated by bathing. PMID- 27668180 TI - A case report on the efficacy of vigabatrin analogue (1S, 3S)-3-amino-4 difluoromethylenyl-1-cyclopentanoic acid (CPP-115) in a patient with infantile spasms. AB - West Syndrome is characterized by infantile spasms, a hypsarrhythmic electroencephalogram (EEG) pattern, and a poor neurodevelopmental prognosis. First-line treatments include adrenocorticotrophic hormone (ACTH) and vigabatrin, but adverse effects often limit their use. CPP-115 is a high-affinity vigabatrin analogue developed to increase therapeutic potency and to limit retinal toxicity. Here, we present a child treated with CPP-115 through an investigational new drug protocol who experienced a marked reduction of seizures with no evidence of retinal dysfunction. Given the potential consequences of ongoing infantile spasms and the limitations of available treatments, further assessment of CPP-115 is warranted. PMID- 27668181 TI - Individualizing therapies with responsive epilepsy neurostimulation - A mirtazapine case study of hippocampal excitability. AB - OBJECTIVES: This study aimed to investigate mirtazapine-induced changes in responsive neurostimulator (RNS) recordings in a patient with epilepsy. MATERIALS AND METHODS: Cortical detection/stimulation counts from an RNS implanted in a patient with bitemporal epilepsy were matched to mirtazapine use to see if that drug altered hippocampal excitability. RESULTS: Mirtazapine decreased hippocampal stability; when mirtazapine was held after a washout period, DSC counts declined, but when it was retrialed, DSC counts increased. Responsive epilepsy neurostimulator system data helped design an optimal and individualized medication regimen for our patient with drug-resistant focal epilepsy. CONCLUSIONS: Responsive neurostimulator systems in epilepsy may assess a medication's effect on hippocampal excitability. Mirtazapine worsened hippocampal excitability in a patient with bitemporal epilepsy. PMID- 27668182 TI - Unusual atypical language lateralization. AB - Determining the language-dominant hemisphere is essential for planning epilepsy surgery. A 60-year-old right-handed woman with epilepsy since age 16 failed a partial right anterior lobectomy at age 21. Later, a brain MRI found extensive right-sided cortical dysplasia and periventricular heterotopia. Subsequently, prolonged video-EEG monitoring localized her seizures to the right temporoparietal region. Functional MRI was inconclusive in lateralizing her language, prompting a Wada test, which strongly lateralized language to the right. This unique case of atypical language representation in a right-handed individual with an extensive right-hemispheric congenital malformation and seizure focus illustrates the important thorough presurgical language assessment. PMID- 27668183 TI - Draft genome sequence of the extremely halophilic Halorubrum sp. SAH-A6 isolated from rock salts of the Danakil depression, Ethiopia. AB - The draft genome sequence of Halorubrum sp. SAH-A6, isolated from commercial rock salts of the Danakil depression, Ethiopia. The genome comprised 3,325,770 bp, with the G + C content of 68.0%. The strain has many genes which are responsible for secondary metabolites biosynthesis, transport and catabolism as compared to other Halorubrum archaea members. Abundant genes responsible for numerous transport systems, solute accumulation, and aromatic/sulfur decomposition were detected. The first genomic analysis encourages further research on comparative genomics, and biotechnological applications. The NCBI accession number for this genome is SAMN04278861 and ID: 4278861 and strain deposited with accession number KCTC 43215. PMID- 27668184 TI - Transcriptome profiling of Curcuma longa L. cv. Suvarna. AB - Turmeric is an economically valued crop, because of its utility in the food, pharmaceutical industries and Ayurvedic medicine, attracts the attention in many areas of research work. In the present study, we executed resequencing through transcriptome assembly of the turmeric cultivar Suvarna (CL_Suv_10). Resequencing of Suvarna variety has generated 5 Gbases raw data with 75 bp paired-end sequence. The raw data has been submitted to SRA database of NCBI with accession number SRR4042181. Reads were assembled using Cufflinks-2.2.1 tool which ended up with 42994 numbers of transcripts. The length of transcripts ranged from 83 to15565, with a N50 value 1216 and median transcript length 773. The transcripts were annotated through number of databases. For the first time transcriptome profiling of cultivar Suvarna has been done, which could help towards identification of single nucleotide polymorphisms (SNPs) between Suvarna and other turmeric cultivars for its authentic identification. PMID- 27668185 TI - De novo transcriptome assembly of mangosteen (Garcinia mangostana L.) fruit. AB - Garcinia mangostana L. (Mangosteen), of the family Clusiaceae, is one of the economically important tropical fruits in Indonesia. In the present study, we performed de novo transcriptomic analysis of Garcinia mangostana L. through RNA Seq technology. We obtained the raw data from 12 libraries through Ion Proton System. Clean reads of 191,735,809 were obtained from 307,634,890 raw reads. The raw data obtained in this study can be accessible in DDBJ database with accession number of DRA005014 with bioproject accession number of PRJDB5091. We obtained 268,851 transcripts as well as 155,850 unigenes, having N50 value of 555 and 433 bp, respectively. Transcript/unigene length ranged from 201 to 5916 bp. The unigenes were annotated with two main databases from NCBI and UniProtKB, respectively having annotated-sequences of 73,287 and 73,107, respectively. These transcriptomic data will be beneficial for studying transcriptome of Garcinia mangostana L. PMID- 27668186 TI - Nephrocalcinosis and retinal dystrophy, rare manifestations of MPV17-related mitochondrial depletion syndrome? PMID- 27668187 TI - Approach to the management of rare clinical presentations of macroprolactinomas in reproductive-aged women. AB - OBJECTIVE: To describe 2 cases of macroprolactinomas with atypical presentation in women desiring pregnancy that illustrate important considerations in the management approach for macroprolactinomas in reproductive-aged women. PATIENTS: Case 1 was a 26-year-old woman referred to our institution for possible tumor resection after pituitary apoplexy during her first pregnancy. Instead, she underwent treatment with cabergoline for a year with goals of normalization of prolactin and decrease in tumor size to <1 cm before trying to conceive. Case 2 was an 18-year-old woman with a macroprolactinoma intolerant to dopamine agonists. She underwent stereotactic radiosurgery, with marked reduction in tumor size and normalization of prolactin levels. She conceived and delivered a healthy infant 3 years after radiosurgery. CONCLUSION: Management of macroprolactinomas in women desiring pregnancy requires careful consideration of alternatives to surgery which could impair pituitary function and fertility and awareness of treatment goals that can minimize the risks for pituitary apoplexy and vision loss during pregnancy. It is important to increase awareness of these options prior to initiation of treatment and conception. PMID- 27668189 TI - Reader's Forum. PMID- 27668188 TI - Impact of Smoking on Nutrition and the Food Poverty Level in Tanzania. AB - This study considers the effect of household cigarette expenditure on food poverty indicators in Tanzania. We first compare expenditure patterns as well as the household size of non-smokers and smokers. We find that the majority of non smokers and smokers have low incomes, and that the mean total per capita expenditure (proxy for income) of non-smokers is slightly higher than those of smokers. On the other hand, the mean household size of non-smokers was smaller compared to that of smokers suggesting that smokers should have spent more on food. Next, we estimate and compare daily calorie intake between both groups. Almost 19 percent of non-smokers were found to be below the poverty line. The corresponding value for smokers was almost 24 percent. Estimates from a multiple linear regression on the determinants of per capita daily calorie intake reveal that per capita cigarette consumption appears to negatively affect daily calorie intake significantly. Given that the majority of all respondents belong to a low income group, this suggests that expenditure on cigarettes may be at the expense of calorie intake. PMID- 27668190 TI - Sphenoid bone changes in rapid maxillary expansion assessed with cone-beam computed tomography. AB - OBJECTIVE: Rapid maxillary expansion (RME) is used to expand the maxilla and increase arch perimeter; yet, there are few reports on its effects on the sphenoid bone. With cone-beam computed topography (CBCT), it is possible to visualize sphenoid bone changes. The purpose of this study was to investigate sphenoid bone changes observed in conjunction with RME treatments, using CBCT. METHODS: Sixty patients (34 women and 26 men, aged 11-17 years) underwent RME as part of their orthodontic treatment. Patients were randomly assigned to one of three groups: a tooth-anchored group, a bone-anchored group, or a control group. Initial CBCT scans were performed preceding the RME treatment (T1) and again directly after the completion of expansion (T2). Statistical analysis included ANOVA, descriptive statistics, and the intraclass correlation coefficient (ICC). RESULTS: The reliability of the landmark location was at least 0.783, and the largest ICC mean measurement error was 2.32 mm. With regard to distances, the largest change was 0.78 mm, which was not statistically significant (p > 0.05). Statistical significance was established in patient groups of the same sex and treatment type for the following distance measurements: right anterior lateral pterygoid plate to the right edge of the hypophyseal fossa (d2), anterior distance between the medial pterygoid plates (d4), and anterior distance between the left medial and lateral plates (d8). CONCLUSIONS: In this study, there were no clinically significant changes in the sphenoid bone due to RME treatments regardless of sex or treatment type. PMID- 27668191 TI - Three-dimensional evaluation of tooth movement in Class II malocclusions treated without extraction by orthodontic mini-implant anchorage. AB - OBJECTIVE: The aim of this study was to analyze tooth movement and arch width changes in maxillary dentition following nonextraction treatment with orthodontic mini-implant (OMI) anchorage in Class II division 1 malocclusions. METHODS: Seventeen adult patients diagnosed with Angle's Class II division 1 malocclusion were treated by nonextraction with OMIs as anchorage for distalization of whole maxillary dentition. Three-dimensional virtual maxillary models were superimposed with the best-fit method at the pretreatment and post-treatment stages. Linear, angular, and arch width variables were measured using Rapidform 2006 software, and analyzed by the paired t-test. RESULTS: All maxillary teeth showed statistically significant movement posteriorly (p < 0.05). There were no significant changes in the vertical position of the maxillary teeth, except that the second molars were extruded (0.86 mm, p < 0.01). The maxillary first and second molars were rotated distal-in (4.5 degrees , p < 0.001; 3.0 degrees , p < 0.05, respectively). The intersecond molar width increased slightly (0.1 mm, p > 0.05) and the intercanine, interfirst premolar, intersecond premolar, and interfirst molar widths increased significantly (2.2 mm, p < 0.01; 2.2 mm, p < 0.05; 1.9 mm, p < 0.01; 2.0 mm, p < 0.01; respectively). CONCLUSIONS: Nonextraction treatment with OMI anchorage for Class II division 1 malocclusions could retract the whole maxillary dentition to achieve a Class I canine and molar relationship without a change in the vertical position of the teeth; however, the second molars were significantly extruded. Simultaneously, the maxillary arch was shown to be expanded with distal-in rotation of the molars. PMID- 27668192 TI - A three-dimensional finite element analysis of molar distalization with a palatal plate, pendulum, and headgear according to molar eruption stage. AB - OBJECTIVE: This study aimed to (1) evaluate the effects of maxillary second and third molar eruption status on the distalization of first molars with a modified palatal anchorage plate (MPAP), and (2) compare the results to the outcomes of the use of a pendulum and that of a headgear using three-dimensional finite element analysis. METHODS: Three eruption stages were established: an erupting second molar at the cervical one-third of the first molar root (Stage 1), a fully erupted second molar (Stage 2), and an erupting third molar at the cervical one third of the second molar root (Stage 3). Retraction forces were applied via three anchorage appliance models: an MPAP with bracket and archwire, a bone anchored pendulum appliance, and cervical-pull headgear. RESULTS: An MPAP showed greater root movement of the first molar than crown movement, and this was more noticeable in Stages 2 and 3. With the other devices, the first molar showed distal tipping. Transversely, the first molar had mesial-out rotation with headgear and mesial-in rotation with the other devices. Vertically, the first molar was intruded with an MPAP, and extruded with the other appliances. CONCLUSIONS: The second molar eruption stage had an effect on molar distalization, but the third molar follicle had no effect. The application of an MPAP may be an effective treatment option for maxillary molar distalization. PMID- 27668194 TI - The effects of alveolar bone loss and miniscrew position on initial tooth displacement during intrusion of the maxillary anterior teeth: Finite element analysis. AB - OBJECTIVE: The aim of this study was to determine the optimal loading conditions for pure intrusion of the six maxillary anterior teeth with miniscrews according to alveolar bone loss. METHODS: A three-dimensional finite element model was created for a segment of the six anterior teeth, and the positions of the miniscrews and hooks were varied after setting the alveolar bone loss to 0, 2, or 4 mm. Under 100 g of intrusive force, initial displacement of the individual teeth in three directions and the degree of labial tilting were measured. RESULTS: The degree of labial tilting increased with reduced alveolar bone height under the same load. When a miniscrew was inserted between the two central incisors, the amounts of medial-lateral and anterior-posterior displacement of the central incisor were significantly greater than in the other conditions. When the miniscrews were inserted distally to the canines and an intrusion force was applied distal to the lateral incisors, the degree of labial tilting and the amounts of displacement of the six anterior teeth were the lowest, and the maximum von Mises stress was distributed evenly across all the teeth, regardless of the bone loss. CONCLUSIONS: Initial tooth displacement similar to pure intrusion of the six maxillary anterior teeth was induced when miniscrews were inserted distal to the maxillary canines and an intrusion force was applied distal to the lateral incisors. In this condition, the maximum von Mises stresses were relatively evenly distributed across all the teeth, regardless of the bone loss. PMID- 27668193 TI - Evaluation of stability after pre-orthodontic orthognathic surgery using cone beam computed tomography: A comparison with conventional treatment. AB - OBJECTIVE: The aim of this study was to evaluate the skeletal and dental changes after intraoral vertical ramus osteotomy (IVRO) with and without presurgical orthodontics by using cone-beam computed tomography (CBCT). METHODS: This retrospective cohort study included 24 patients (mean age, 22.1 years) with skeletal Class III malocclusion who underwent bimaxillary surgery with IVRO. The patients were divided into the preorthodontic orthognathic surgery (POGS) group (n = 12) and conventional surgery (CS) group (n = 12). CBCT images acquired preoperatively, 1 month after surgery, and 1 year after surgery were analyzed to compare the intergroup differences in postoperative three-dimensional movements of the maxillary and mandibular landmarks and the changes in lateral cephalometric variables. RESULTS: Baseline demographics (sex and age) were similar between the two groups (6 men and 6 women in each group). During the postsurgical period, the POGS group showed more significant upward movement of the mandible (p < 0.05) than did the CS group. Neither group showed significant transverse movement of any of the skeletal landmarks. Moreover, none of the dental and skeletal variables showed significant intergroup differences 1 year after surgery. CONCLUSIONS: Compared with CS, POGS with IVRO resulted in significantly different postsurgical skeletal movement in the mandible. Although both groups showed similar skeletal and dental outcomes at 1 year after surgery, upward movement of the mandible during the postsurgical period should be considered to ensure a more reliable outcome after POGS. PMID- 27668195 TI - Quantitative evaluation of midpalatal suture maturation via fractal analysis. AB - OBJECTIVE: The purpose of this study was to determine whether the results of fractal analysis can be used as criteria for midpalatal suture maturation evaluation. METHODS: The study included 131 subjects aged over 18 years of age (range 18.1-53.4 years) who underwent cone-beam computed tomography. Skeletonized images of the midpalatal suture were obtained via image processing software and used to calculate fractal dimensions. Correlations between maturation stage and fractal dimensions were calculated using Spearman's correlation coefficient. Optimal fractal dimension cut-off values were determined using a receiver operating characteristic curve. RESULTS: The distribution of maturation stages of the midpalatal suture according to the cervical vertebrae maturation index was highly variable, and there was a strong negative correlation between maturation stage and fractal dimension (-0.623, p < 0.001). Fractal dimension was a statistically significant indicator of dichotomous results with regard to maturation stage (area under curve = 0.794, p < 0.001). A test in which fractal dimension was used to predict the resulting variable that splits maturation stages into ABC and D or E yielded an optimal fractal dimension cut-off value of 1.0235. CONCLUSIONS: There was a strong negative correlation between fractal dimension and midpalatal suture maturation. Fractal analysis is an objective quantitative method, and therefore we suggest that it may be useful for the evaluation of midpalatal suture maturation. PMID- 27668196 TI - Diagnostic methods for assessing maxillary skeletal and dental transverse deficiencies: A systematic review. AB - OBJECTIVE: To evaluate the accuracy and reliability of the diagnostic tools available for assessing maxillary transverse deficiencies. METHODS: An electronic search of three databases was performed from their date of establishment to April 2015, with manual searching of reference lists of relevant articles. Articles were considered for inclusion if they reported the accuracy or reliability of a diagnostic method or evaluation technique for maxillary transverse dimensions in mixed or permanent dentitions. Risk of bias was assessed in the included articles, using the Quality Assessment of Diagnostic Accuracy Studies tool-2. RESULTS: Nine articles were selected. The studies were heterogeneous, with moderate to low methodological quality, and all had a high risk of bias. Four suggested that the use of arch width prediction indices with dental cast measurements is unreliable for use in diagnosis. Frontal cephalograms derived from cone-beam computed tomography (CBCT) images were reportedly more reliable for assessing intermaxillary transverse discrepancies than posteroanterior cephalograms. Two studies proposed new three-dimensional transverse analyses with CBCT images that were reportedly reliable, but have not been validated for clinical sensitivity or specificity. No studies reported sensitivity, specificity, positive or negative predictive values or likelihood ratios, or ROC curves of the methods for the diagnosis of transverse deficiencies. CONCLUSIONS: Current evidence does not enable solid conclusions to be drawn, owing to a lack of reliable high quality diagnostic studies evaluating maxillary transverse deficiencies. CBCT images are reportedly more reliable for diagnosis, but further validation is required to confirm CBCT's accuracy and diagnostic superiority. PMID- 27668197 TI - Maternal uterine artery Doppler in the first and second trimesters as screening method for hypertensive disorders and adverse perinatal outcomes in low-risk pregnancies. AB - OBJECTIVE: To assess the maternal demographic characteristics and uterine artery (UA) Doppler parameters at first and second trimesters of pregnancy as predictors for hypertensive disorders (HDs) and adverse perinatal outcomes. METHODS: This prospective cohort study comprised 162 singleton low-risk women undergoing routine antenatal care. The left and right UA were assessed by color and pulsed Doppler and the mean pulsatility and resistance indices as well as the presence of a bilateral protodiastolic notch were recorded at 11 to 14 and 20 to 24 weeks' gestation. Multilevel regression analysis was used to determine the effects of maternal characteristics and abnormal UA Doppler parameters on the incidence of HD, small for gestational age newborn, cesarean section rate, Apgar score <7 at 1st and 5th minute, and admission to the neonatal intensive care unit. RESULTS: Fifteen women (9.2%) developed HD. UA mean resistance index (RI), UA mean pulsatility index, and parity were independent predictors of HD. Compared to the pregnancies with a normal UA mean RI at the first and second trimesters, pregnancies with UA mean RI >95th percentile only at the first trimester showed an increased risk for HD (odds ratio, 23.25; 95% confidence interval, 3.47 to 155.73; P<0.01). Similar result was found for UA mean pulsatility index >95th percentile (odds ratio, 9.84; 95% confidence interval, 1.05 to 92.10; P=0.05). The model including maternal age, maternal and paternal ethnicity, occupation, parity and UA mean RI increased the relative risk for HD (area under receiver operating characteristics, 0.81). CONCLUSION: A first-trimester screening combining maternal characteristics and UA Doppler parameters is useful to predict HD in a low-risk population. PMID- 27668198 TI - Screening for chromosomal abnormalities using combined test in the first trimester of pregnancy. AB - OBJECTIVE: This study was designed to review the screening performance of combined test at the Ewha Womans University Mokdong hospital. METHODS: All women admitted for routine antenatal care between January 1st 2008 and December 31st 2012 with a known pregnancy outcome were included in this study, totaling 1,156 women with singleton pregnancies presenting at 10 to 13 weeks of gestation. Women were offered screening using a combination of maternal serum pregnancy-associated plasma protein-A, free beta-human chorionic gonadotropin and fetal nuchal translucency thickness. Those with an estimated risk of >=1 in 250 of carrying a fetus with trisomy 21 or >=1 in 300 risk of trisomy 18 were offered genetic counseling with the option of an invasive diagnostic test. RESULTS: The median of gestational age was 11+3 weeks, the median of crown-rump length was 47.1 mm, and the median age of the women was 31 years. The detection rate was 80% for trisomy 21 (4 of 5) and 100% for trisomy 13 and 18 (all 2). The false-positive rate was 7.73% for trisomy 21 and 1.21% for trisomy 18. CONCLUSION: This study was the first large population study performed with the aim of analyzing the performance of the combined test in Korea. This study demonstrated that the detection rates and other figures of the first trimester combined test are comparable to the results reported in other papers worldwide. Consequently, if strict conditions for good screening outcomes are achieved, the first trimester combined test might well be the earliest detectable screening, improving detection rates without increasing karyotyping or economic and other implications that inevitably ensue. PMID- 27668199 TI - The association between polycystic ovary syndrome and breast cancer: a meta analysis. AB - OBJECTIVE: The results of epidemiological studies investigated the association between polycystic ovary syndrome (PCOS) and the breast cancer are inconsistent. This meta-analysis was conducted to estimate the association between PCOS and the breast cancer risk. We searched PubMed, Web of Science, and Scopus for observational studies until June 2015. Data were independently extracted and analyzed using 95% odds ratio, and confidence intervals (CIs) based on the random effects models. METHODS: We identified 970 references and conducted eight studies with 45,470 participants and 243,064 person- year. RESULTS: The association between PCOS and the breast cancer risk in case-control studies 0.87 (95% CI, 0.44 to 1.31) and that of cohort studies was estimated 1.18 (95% CI, 0.93 to 1.43). CONCLUSION: This meta-analysis demonstrated that PCOS no does increase the risk of breast cancer. Further prospective cohort studies are needed to provide convincing evidence in order to PCOS can increase or not effect on the risk of the breast cancer. PMID- 27668200 TI - Surgical and obstetrical outcomes after laparoscopic radical trachelectomy and pelvic lymphadenectomy for early cervical cancer. AB - OBJECTIVE: The aim of this study was to evaluate the surgical and obstetrical outcomes of patients with early cervical cancer who underwent laparoscopic radical trachelectomy and pelvic lymphadenectomy. METHODS: We analyzed data from women who underwent laparoscopic radical trachelectomy and pelvic lymphadenectomy between July 2000 and October 2014. RESULTS: Of a total of 12 patients, 91.7% were FIGO (International Federation of Gynecology and Obstetrics) stages IA2 and IB1. Seven patients (58.3%) had squamous cell carcinoma. The median tumor size was 1.87 cm (range, focal to 4.6 cm) and two patients (16.7%) had a tumor lager than 2 cm. Lymphovascular space invasion in the tumor lesion was reported in six patients (50%). The following surgical complications were observed: neurogenic bladder (one patient), hemoperitoneum (one patient), and infection (one patient). A total of 33.3% had attempted to conceive, resulting in two pregnancies and two healthy babies. All pregnancies were achieved by in vitro fertilization and embryo transfer. Each woman underwent cesarean delivery because of premature pre labor rupture of membranes at gestational weeks 27.3 and 33.3. After a median follow-up time of 4.4 years (range, 1 to 8 years), there were no recurrences or deaths. CONCLUSION: Laparoscopic radical trachelectomy and pelvic lymphadenectomy should be offered as an alternative treatment for women with early stage cervical cancer who want to preserve their fertility. PMID- 27668201 TI - Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women. AB - OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-beta2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03+/-4.30 years, and mean number of miscarriages was 2.69+/-1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63+/-5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group. PMID- 27668202 TI - Umbilical cord ulceration: An underdiagnosed entity. AB - Umbilical cord ulceration is a rare condition presenting with sudden fetal bradycardia due to fetal hemorrhage and in most cases leading to intrauterine death. A strong association with intestinal atresia has been reported. Most cases present after 30 weeks of gestation, with preterm labor or rupture of membranes followed by sudden fetal bradycardia. We report two such cases of umbilical cord ulceration and review the available literature. One of the cases interestingly presented at 26 weeks, much earlier than what is reported in the world literature. In view of high perinatal mortality and morbidity, awareness of this condition is mandatory for timely and appropriate management to improve the fetal outcome. PMID- 27668203 TI - An extremely rare case of prenatally diagnosed absent both aortic and pulmonary valves. AB - We describe a case of absent aortic and pulmonary valves, diagnosed at 16.4 weeks of gestation. Fetal echocardiography showed cardiomegaly with dilated both ventricles. No valve leaflets were observed in the aorta and pulmonary artery, and a typical to-and-fro flow pattern was noted in both great arteries on color Doppler imaging. Fetal hydrops was also detected. Follow-up ultrasonographic evaluation at 19 weeks demonstrated intrauterine fetal death. Postmortem autopsy revealed the absence of both aortic and pulmonary valve leaflets. To the best of our knowledge, this is the earliest diagnosed case of absent both aortic and pulmonary valves and only the second case to be diagnosed prenatally. PMID- 27668204 TI - Hepatic infarction in a pregnant woman with antiphospholipid syndrome and triple antibody positivity: A case report focusing on catastrophic antiphospholipid syndrome. AB - Pregnant women with antiphospholipid syndrome (APS) carry a high risk of arterial or venous thrombosis. Such thrombotic conditions occur more frequently in patients with triple positivity to antiphospholipid antibodies or with high antibody titers. Hepatic infarction is a rare complication in pregnant women with APS, and it sometimes mimics HELLP syndrome. This report describes a preeclamptic pregnant woman with APS who had high titers of three antiphospholipid antibodies. She experienced severe epigastric pain with elevated liver enzymes; in addition, she had tachycardia and tachypnea. The clinical findings suggested hepatic infarction and pulmonary thromboembolism, a partial manifestation of catastrophic APS. Therefore, she underwent emergent cesarean section at 25+2 weeks of gestation. After the delivery, her laboratory test indicated HELLP-like features, and computed tomography confirmed hepatic infarction and pulmonary micro thromboembolism. Here, we report a case of a partial manifestation of catastrophic APS in a pregnant woman with triple antibody positivity, including a brief literature review. PMID- 27668205 TI - Aortic dissection accompanied by preeclampsia in a postpartum young woman. AB - Aortic dissection is very rare in obstetrics, but it is a fatal disease. A 37 weeks primigravida woman with dyspnea and pitting edema presented to our emergency room. The patient was diagnosed with preeclampsia and underwent an emergency cesarean section under spinal anesthesia. The patient complained of severe dyspnea after the cesarean section, and the chest computed tomography scan was done. With the finding of aortic dissection, cardiopulmonary arrest occurred 5 hours after the cesarean section, and the patient died without reaction to cardio-pulmonary resuscitation. If a patient with preeclampsia complains of severe dyspnea or chest pain, aortic dissection needs to be suspected and a diagnosis should not be delayed. PMID- 27668206 TI - Fetal neuroblastoma: ultrasonography and magnetic resonance imaging findings in the prenatal and postnatal IV-S stage. AB - We report a case of a fetus with an ultrasonography diagnosis of a neuroblastoma during a routine third trimester fetal scan, which presented as a hyperechogenic nodule located above the right kidney. No other abnormalities were found in the ultrasonography scan; however, the follow-up ultrasonography during the 36th week of gestation revealed that the lesion had doubled in size. At the same time, magnetic resonance imaging demonstrated a round mass in the topography of the right adrenal gland with a low signal on T1-weighted images and slightly high signal on T2-weighted images, causing a slight inferior displacement of the kidney. The liver had enlarged and had heterogeneous signal intensity, predominantly hypointense on T2-weighted sequences. Based on these findings, a diagnosis of congenital adrenal neuroblastoma with liver metastases was suggested. A newborn male was delivered by cesarean section 2 weeks later. The physical examination of the neonate revealed abdominal distention and hepatomegaly. The infant had a clinical follow-up in which no surgical or medical intervention was required. At 5 months of age, the infant was asymptomatic with a normal physical examination. PMID- 27668207 TI - Cervical xanthogranuloma in a case of postmenopausal pyometra. AB - Xanthogranuloma is a non-neoplastic presentation of chronic inflammation commonly seen in gallbladder, kidney and rarely seen in genital organs. Only one case has been reported in cervix. Here, we report a case of 60-year-old postmenopausal lady who presented with history of fever and purulent discharge per-vaginum. On speculum examination, cervix had an ulcer extending from 3 to 5 o'clock position. Uterus was bulky. On probing the ulcer, a 1-cm deep sinus was identified. Ultrasound showed enlarged uterus and fluid collection suggestive of pyometra. Pyometra was drained and cervical biopsy was taken from the ulcerated lesion; histopathology revealed granulomatous inflammation with predominantly xanthous cells suggestive of tuberculosis. High index of clinical suspicion needs to be maintained in abnormal cervix. It is a perplexing and rare entity for a clinician and also a diagnosis of exclusion; only histopathology can help for diagnosis. It mimics like malignancy and chronic infections. PMID- 27668208 TI - Primary malignant melanoma of cervix and vagina. AB - Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70 year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains. PMID- 27668209 TI - High-intensity focused ultrasound combined with hysteroscopic resection to treat retained placenta accreta. AB - We present a case of retained placenta accreta treated by high-intensity focused ultrasound (HIFU) ablation followed by hysteroscopic resection. The patient was diagnosed as submucosal myoma based on ultrasonography in local clinic. Pathologic examination of several pieces of tumor mass from the hysteroscopic procedure revealed necrotic chorionic villi with calcification. HIFU was performed using an ultrasound-guided HIFU tumor therapeutic system. The ultrasound machine had been used for real-time monitoring of the HIFU procedure. After HIFU treatment, no additional vaginal bleeding or complications were observed. A hysteroscopic resection was performed to remove ablated placental tissue 7 days later. No abnormal vaginal bleeding or discharge was seen after the procedure. The patient was stable postoperatively. We proposed HIFU and applied additional hysteroscopic resection for a safe and effective method for treating retained placenta accreta to prevent complications from the remaining placental tissue and to improve fertility options. PMID- 27668210 TI - Erratum: Figure Correction. AB - [This corrects the article on p. 245 in vol. 59, PMID: 27200318.]. PMID- 27668211 TI - The Eukaryotic Microbiome: Origins and Implications for Fetal and Neonatal Life. AB - All eukaryotic organisms are holobionts representing complex collaborations between the entire microbiome of each eukaryote and its innate cells. These linked constituencies form complex localized and interlocking ecologies in which the specific microbial constituents and their relative abundance differ substantially according to age and environmental exposures. Rapid advances in microbiology and genetic research techniques have uncovered a significant previous underestimate of the extent of that microbial contribution and its metabolic and developmental impact on holobionts. Therefore, a re-calibration of the neonatal period is suggested as a transitional phase in development that includes the acquisition of consequential collaborative microbial life from extensive environmental influences. These co-dependent, symbiotic relationships formed in the fetal and neonatal stages extend into adulthood and even across generations. PMID- 27668213 TI - The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation. AB - Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost importance to develop integrative biomaterials based on multifunctional biopolymers and nanosystem for their practical and successful clinical translation. PMID- 27668212 TI - Metal Cations in G-Quadruplex Folding and Stability. AB - This review is focused on the structural and physicochemical aspects of metal cation coordination to G-Quadruplexes (GQ) and their effects on GQ stability and conformation. G-quadruplex structures are non-canonical secondary structures formed by both DNA and RNA. G-quadruplexes regulate a wide range of important biochemical processes. Besides the sequence requirements, the coordination of monovalent cations in the GQ is essential for its formation and determines the stability and polymorphism of GQ structures. The nature, location, and dynamics of the cation coordination and their impact on the overall GQ stability are dependent on several factors such as the ionic radii, hydration energy, and the bonding strength to the O6 of guanines. The intracellular monovalent cation concentration and the localized ion concentrations determine the formation of GQs and can potentially dictate their regulatory roles. A wide range of biochemical and biophysical studies on an array of GQ enabling sequences have generated at a minimum the knowledge base that allows us to often predict the stability of GQs in the presence of the physiologically relevant metal ions, however, prediction of conformation of such GQs is still out of the realm. PMID- 27668214 TI - Super-Resolution Imaging of Plasma Membrane Proteins with Click Chemistry. AB - Besides its function as a passive cell wall, the plasma membrane (PM) serves as a platform for different physiological processes such as signal transduction and cell adhesion, determining the ability of cells to communicate with the exterior, and form tissues. Therefore, the spatial distribution of PM components, and the molecular mechanisms underlying it, have important implications in various biological fields including cell development, neurobiology, and immunology. The existence of confined compartments in the plasma membrane that vary on many length scales from protein multimers to micrometer-size domains with different protein and lipid composition is today beyond all questions. As much as the physiology of cells is controlled by the spatial organization of PM components, the study of distribution, size, and composition remains challenging. Visualization of the molecular distribution of PM components has been impeded mainly due to two problems: the specific labeling of lipids and proteins without perturbing their native distribution and the diffraction-limit of fluorescence microscopy restricting the resolution to about half the wavelength of light. Here, we present a bioorthogonal chemical reporter strategy based on click chemistry and metabolic labeling for efficient and specific visualization of PM proteins and glycans with organic fluorophores in combination with super resolution fluorescence imaging by direct stochastic optical reconstruction microscopy (dSTORM) with single-molecule sensitivity. PMID- 27668219 TI - Clinical perception and simple laboratory tests: do not mistake the finger pointing at the moon. PMID- 27668215 TI - Identifying and Visualizing Macromolecular Flexibility in Structural Biology. AB - Structural biology comprises a variety of tools to obtain atomic resolution data for the investigation of macromolecules. Conventional structural methodologies including crystallography, NMR and electron microscopy often do not provide sufficient details concerning flexibility and dynamics, even though these aspects are critical for the physiological functions of the systems under investigation. However, the increasing complexity of the molecules studied by structural biology (including large macromolecular assemblies, integral membrane proteins, intrinsically disordered systems, and folding intermediates) continuously demands in-depth analyses of the roles of flexibility and conformational specificity involved in interactions with ligands and inhibitors. The intrinsic difficulties in capturing often subtle but critical molecular motions in biological systems have restrained the investigation of flexible molecules into a small niche of structural biology. Introduction of massive technological developments over the recent years, which include time-resolved studies, solution X-ray scattering, and new detectors for cryo-electron microscopy, have pushed the limits of structural investigation of flexible systems far beyond traditional approaches of NMR analysis. By integrating these modern methods with powerful biophysical and computational approaches such as generation of ensembles of molecular models and selective particle picking in electron microscopy, more feasible investigations of dynamic systems are now possible. Using some prominent examples from recent literature, we review how current structural biology methods can contribute useful data to accurately visualize flexibility in macromolecular structures and understand its important roles in regulation of biological processes. PMID- 27668216 TI - Segrosome Complex Formation during DNA Trafficking in Bacterial Cell Division. AB - Bacterial extrachromosomal DNAs often contribute to virulence in pathogenic organisms or facilitate adaptation to particular environments. The transmission of genetic information from one generation to the next requires sufficient partitioning of DNA molecules to ensure that at least one copy reaches each side of the division plane and is inherited by the daughter cells. Segregation of the bacterial chromosome occurs during or after replication and probably involves a strategy in which several protein complexes participate to modify the folding pattern and distribution first of the origin domain and then of the rest of the chromosome. Low-copy number plasmids rely on specialized partitioning systems, which in some cases use a mechanism that show striking similarity to eukaryotic DNA segregation. Overall, there have been multiple systems implicated in the dynamic transport of DNA cargo to a new cellular position during the cell cycle but most seem to share a common initial DNA partitioning step, involving the formation of a nucleoprotein complex called the segrosome. The particular features and complex topologies of individual segrosomes depend on both the nature of the DNA binding protein involved and on the recognized centromeric DNA sequence, both of which vary across systems. The combination of in vivo and in vitro approaches, with structural biology has significantly furthered our understanding of the mechanisms underlying DNA trafficking in bacteria. Here, I discuss recent advances and the molecular details of the DNA segregation machinery, focusing on the formation of the segrosome complex. PMID- 27668218 TI - The Use of Adipose-Derived Progenitor Cells and Platelet-Rich Plasma Combination for the Treatment of Supraspinatus Tendinopathy in 55 Dogs: A Retrospective Study. AB - OBJECTIVE: To report clinical findings and outcomes for 55 dogs with supraspinatus tendinopathy (ST) treated with adipose-derived progenitor cells and platelet-rich plasma (ADPC-PRP) therapy. METHODS: Medical records of client-owned dogs diagnosed with ST that were treated with ADPC-PRP combination therapy were reviewed from 2006 to 2013. Data collected included signalment, medical history, limb involvement, prior treatments, physical and orthopedic examination, objective temporospatial gait analysis findings, diagnostic imaging results (radiography, magnetic resonance imaging, musculoskeletal ultrasonography), arthroscopy findings, and outcome. RESULTS: Following ultrasound-guided injection of ADPC-PRP, objective gait analysis was available on 25 of the 55 dogs at 90 days post ADPC-PRP therapy. Following treatment, a significant increase in total pressure index percentage (TPI%) was noted in the injured (treated) forelimb at 90 days post treatment (p = 0.036). At 90 days following treatment, 88% of cases had no significant difference in TPI% of the injured limb to the contralateral limb. The remaining 12% of cases had significantly improved (p = 0.036). Bilateral shoulder diagnostic musculoskeletal ultrasound revealed a significant reduction in tendon size (CSA) in the treated tendon at 90 days following treatment when compared to the initial CSA (p = 0.005). All cases showed significant improvement in fiber pattern of the affected supraspinatus tendon by the ultrasound shoulder pathology rating scale. CLINICAL RELEVANCE: These findings suggest that ADPC-PRP therapy should be considered for dogs with ST. PMID- 27668220 TI - Neural networks: further insights into error function, generalized weights and others. AB - The article is a continuum of a previous one providing further insights into the structure of neural network (NN). Key concepts of NN including activation function, error function, learning rate and generalized weights are introduced. NN topology can be visualized with generic plot() function by passing a "nn" class object. Generalized weights assist interpretation of NN model with respect to the independent effect of individual input variables. A large variance of generalized weights for a covariate indicates non-linearity of its independent effect. If generalized weights of a covariate are approximately zero, the covariate is considered to have no effect on outcome. Finally, prediction of new observations can be performed using compute() function. Make sure that the feature variables passed to the compute() function are in the same order to that in the training NN. PMID- 27668217 TI - Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment. AB - In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed, e.g., in the "fly-casting" hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit), are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context. PMID- 27668222 TI - Mitral valve repair with the "respect" approach in dialysis-dependent patients: a single-center experience. AB - BACKGROUND: Morbidity and mortality risks in patients with end-stage renal disease (ESRD) undergoing mitral valve surgery are high; however, little is known regarding the risks and results of mitral valve repair in these patients. METHODS: We retrospectively reviewed the clinical data of dialysis-dependent patients who underwent mitral valve repair with the "respect" approach between April 2012 and April 2015 in our institution. RESULTS: All five identified patients survived and their data were included in the analysis. Follow-up ranged from 3 to 48 months with a median of 24+/-8.9 months. Patients' cardiac function improved postoperatively with two patients in New York Heart Association class I and three patients in class II. Three patients had no or trivial mitral valve regurgitation, two patients had mild regurgitation, and none had moderate or higher regurgitation. Left ventricular end diastolic volume decreased significantly: from 166.2+/-32.7 mL preoperatively to 123.1+/-24.5 mL postoperatively (P<0.001). CONCLUSIONS: With the "respect" approach, mitral valve repair in dialysis-dependent patients with prolapse of the posterior leaflet provided good and stable results; however, appropriate perioperative management was critical in these patients. PMID- 27668221 TI - CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation. AB - BACKGROUND: Ulcerative colitis (UC) is a nonspecific inflammatory disease for which medications and therapeutic strategies have only been moderately successful. CBLB502, a toll-like receptor 5 (TLR5) agonist derived from Salmonella flagellin, exhibits anticancer and radioprotective activities via modulation of TLRs and the nuclear factor kappa B (NF-kappaB) signaling pathway and can protect against acute renal ischemic failure. In this study, we intend to examine the effects of CBLB502 on both TLR responses and the interleukin (IL) and NF-kappaB signaling pathways in UC treatment. METHODS: The UC mouse model was prepared in BALB/c mice by administering 2,4,6-trinitrobenzene sulfonic acid (TNBS). CBLB502 was used as the therapeutic drug. After CBLB502 therapy, the IL and tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. Total RNA and protein of colon samples was extracted. RESULTS: We found that CBLB502 had a distinctive therapeutic effect in the UC model. In control group animals, IL-10 expression in serum was 91.48+/-24.38 ng/mL; this was higher than in the model group (59.36+/-14.46 ng/mL, P<0.05) or the treatment group (54.29+/-5.83 ng/mL, P<0.05). In model group animals, the concentration of TNF-alpha in serum was 140.11+/-12.70 ng/mL, which was lower than protein levels in the control group (173.86+/-29.26 ng/mL, P<0.05). The mRNA levels of TLR1, 2, 3, 4, 6, 7, 8, and 9 in the CBLB502 treatment group were significantly lower than in the model group (P<0.05). Western blot revealed that CBLB502 also reduced NF-kappaB expression in the mouse colon, but that NF-kappaB expression was not significantly lower than the model group. CONCLUSIONS: CBLB502 can reduce mucosal damage induced by TNBS and inhibit inflammation and TLR expression. The inhibition of UC by CBLB502 is strictly TLR-IL-dependent and is dose-dependent within the efficacious dose range. Therefore, our results suggested that CBLB502 might be a candidate drug for the treatment of UC. PMID- 27668223 TI - History of previous knee surgery does not affect the clinical outcomes of primary total knee arthroplasty in an Asian population. AB - BACKGROUND: Patients with a history of previous knee surgeries, such as anterior cruciate ligament reconstruction (ACLR) and high tibial osteotomy (HTO), often have a higher likelihood of requiring a subsequent total knee arthroplasty (TKA). However, there is relatively limited data, especially in the Asian population, on how previous knee surgery could affect the clinical outcomes of TKA. Therefore, this study aims to evaluate the impact of previous knee surgeries on the clinical outcomes of future TKA. METHODS: We reviewed the prospectively-collected data of 303 patients who underwent TKA by a single surgeon from a total joint registry of a tertiary hospital over a period of 5 years. Those with a history of previous knee surgery were identified. The SF-36 Health Survey, Oxford Knee Score (OKS) and Knee Society Score (KSS) were used to evaluate clinical outcomes pre operatively, at 6 months and 2 years. RESULTS: Previous knee surgery did not have a significant impact on the patients' pre-operative baseline clinical scores and body mass index (BMI). Patients with a history of knee surgery undergo TKA at a significantly younger age (mean of 6.6 years younger). On follow-up, patients with a history of knee surgery have similar post-operative outcome scores as those without previous knee surgery. Also, a high proportion of these patients are satisfied with their post-operative results and feel that their expectations have been met. CONCLUSIONS: Patients with previous knee surgery had TKA at a significantly younger age than those without. But these patients have similar clinical and quality of life outcomes after TKA. In addition, a high proportion of these patients are satisfied with the results of surgery and feel that their expectations of TKA are met. This is important for clinicians when counselling patients pre-operatively. PMID- 27668224 TI - Bronchial reacutization and gastroesophageal reflux: is there a potential clinical correlation? AB - BACKGROUND: Pepsin plays a role in gastroesophageal reflux (GER). Aims of this study were to verify if pepsin could be the cause of frequent bronchial exacerbations and to check if the persistence of chronic respiratory symptoms were correlated with pre-existing respiratory diseases. METHODS: From January to May 2016, 42 patients underwent a diagnostic bronchoscopy. All patients had a history of at least one bronchial exacerbation during the previous year. Bronchial lavage fluid specimens were obtained. A semiquantitative assessment of pepsin in the samples was carried out based on the intensity of the test sample. RESULTS: Pepsin was present in 37 patients (88%), but in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD), the finding of pepsin in the bronchoalveolar fluid was 100%. There was a strong positive statistical correlation between pepsin detection and radiological signs of GER (rho=0.662), and between pepsin detection and diagnosis (rho=0.682). No correlation was found between the bacteriology and the presence of pepsin in the airways (rho=0.006). CONCLUSIONS: The presence of pepsin in the airways shows the occurrence of reflux. The persistence of respiratory symptoms by at least 2 months suggest an endoscopic bronchial examination. This straightforward test confirms the cause possible irritation of the airways and may prevent further diagnostic tests, such as an EGD or pH monitoring esophageal. PMID- 27668225 TI - The emerging role of immunotherapy in colorectal cancer. AB - Modulation of the interaction between the immune system and the tumor microenvironment has long been a target of cancer research, including colorectal cancer (CRC). Approaches explored to date include vaccines (autologous, peptide, dendritic cell, viral and bacterial), cytokine therapy, toll-like receptors (TLRs), autologous cell therapy and checkpoint inhibition. Until recently these approaches have been shown to have only modest efficacy in reducing tumor burden. However, significant breakthroughs have been made, with the use of checkpoint inhibitors targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). Immunotherapy now represents a possible avenue of curative treatment for those with chemo-otherwise refractory tumors. Success with this approach to immunotherapy has largely been confined to tumors with high mutational burdens such as melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer. This observation led to the exploration and successful use of checkpoint inhibitors in those with mismatch repair colorectal cancer which have a relatively high mutational burden. Ongoing trials are focused on further exploring the use of checkpoint inhibitors in addition to investigating the various combinations of immunotherapeutic drugs. PMID- 27668226 TI - Use of extracorporeal membranous oxygenator in transcatheter aortic valve replacement. AB - The superiority of transcatheter aortic valve replacement (TAVR) compared with medical therapy for patients with aortic stenosis (AS) who are not suitable candidates for surgery had been proven. Cardiopulmonary bypass (CPB) is rarely used in TAVR. Reports of early use of extracorporeal membranous oxygenator (ECMO) have promising outcomes. ECMO offers the option of cardiac support rescue in case of intraoperative hemodynamic instability and can be instituted in advance when hemodynamic instability is expected. Here we review the English literature about the use of ECMO in TAVR procedures, and discuss the indications and rationale for its use as well as its advantages. PMID- 27668227 TI - PillCam colon capsule endoscopy (PCCE) in colonic diseases. AB - Diseases affecting the colon are common worldwide and can cause a major health problem. Colorectal cancer (CRC) as well as Inflammatory bowel diseases represent a major cause of morbidity and mortality in western countries. PillCam colon capsule endoscopy (PCCE) is a novel and promising technology that can be useful for the screening and monitoring of colonic diseases. In the recent years many articles examined the use of various versions of PCCE-the 1st and 2nd generation versus various other endoscopic or radiologic modalities both for detection of colonic polyps or cancer and in both ulcerative colitis (UC) and Crohn's disease. The aim of the current review is to provide up to date information regarding the use and usefulness of this method in these disease. PMID- 27668229 TI - A rare case of metastatic germ cell tumor to stomach and duodenum masquerading as signet ring cell adenocarcinoma. AB - Adenocarcinomas are the most common cancers affecting stomach. However gastrointestinal stromal tumors (GIST), lymphomas and neuroendocrine tumors (NETs) can also affect the stomach. But stomach is relatively rare site of involvement by metastasis. In this case report a rare metastasis of germ cell tumor (GCT) into stomach is described which clinically and endoscopically masquerade as primary gastric cancers. But detailed clinical examination and vigilant histopathological reporting proves the origin of tumor distant from stomach and thereby change the whole approach of management. PMID- 27668228 TI - Effectiveness of enteral feeding protocol on clinical outcomes in critically ill patients: a study protocol for before-and-after design. AB - INTRODUCTION: Enteral feed is an important component of nutritional therapy in critically ill patients and underfeeding has been associated with adverse outcomes. The article developed an enteral feeding protocol and planed a before and-after comparative trial to explore whether implementation of enteral feeding protocol was able to improve clinical outcomes. METHODS AND ANALYSIS: The study will be conducted in intensive care units (ICUs) of ten tertiary care academic centers. Critically ill patients expected to stay in ICU for over 3 days and require enteral nutrition (EN) were potentially eligible. This is a before-and after study comprising three phases: The first phase is the period without enteral feeding protocol; the second phase involves four-week training program, and the last phase is to perform the protocol in participating centers. We plan to enroll a total of 350 patients to provide an 80% power and 0.05 error rate to detect a 15% reduction of mortality. The primary outcome is 28-day mortality. ETHICS AND DISSEMINATION: Ethical approval to conduct the research has been obtained from all participating centers. Additionally, the results will be published in peer-reviewed journal. TRIAL REGISTRATION: The study was registered at International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry (ISRCTN10583582). PMID- 27668230 TI - Mitral valve replacement in a dialysis-dependent patient. AB - Patients with end-stage renal disease have a higher risk of morbidity and mortality than those without end-stage renal disease in cardiovascular surgery. Poor outcomes are especially found in patients who undergo valve surgery. We report successful mitral valve replacement (MVR) in a dialysis-dependent patient. The patient recovered well at postoperation and had the complication of anticoagulation at follow-up. Based on this successful case, we believe that myocardial protection, prevention of infection, nutritional support, and close monitoring of blood coagulation function are important in dialysis-dependent patients undergoing valve replacement. PMID- 27668231 TI - Autofluorescence bronchoscopy for lung cancer screening: a time to reflect. PMID- 27668232 TI - Preventing or treating anti-EGFR related skin rash with antibiotics? PMID- 27668233 TI - Skin communicates what we deeply feel: antibiotic prophylactic treatment to reduce epidermal growth factor receptor inhibitors induced rash in lung cancer (the Pan Canadian rash trial). PMID- 27668234 TI - Remote ischemic preconditioning to prevent cardiac surgery-related acute kidney injury: how far away from a breakthrough? PMID- 27668235 TI - Radiofrequency ablation is one of safe and effective local control alternative for colorectal pulmonary metastases. PMID- 27668236 TI - Intensive care unit strain should not rush physicians into making inappropriate decisions, but merely reduce the time to the right decisions being made. PMID- 27668237 TI - How to determine the treatment options for lower-pole renal stones. PMID- 27668238 TI - Treatment strategies of epidermal growth factor receptor inhibitor-induced skin toxicities: pre-emptive or reactive? PMID- 27668239 TI - Understanding the sepsis mortality belt: time to buckle down! PMID- 27668240 TI - Blood pressure in acute intra-cerebral hemorrhage. PMID- 27668241 TI - The relentless crumbling of the renin-angiotensin system (RAS)-blockade halo. PMID- 27668242 TI - Living legend in clinical biochemistry-Prof. Giuseppe Lippi: we should have strength to stick to things we do. PMID- 27668243 TI - Gender Differences in Exercise Habits and Quality of Life Reports: Assessing the Moderating Effects of Reasons for Exercise. AB - Men and women report different exercise habits and reasons for exercise. Given that quality of life is affected by exercise habits and reasons for exercise, the present study explored gender differences among these variables. Participants reported quality of life, exercise habits, and motives. Results revealed that women (n = 108) reported significantly higher exercise and quality of life levels than men (n = 72). Women reported exercising for weight loss and toning more than men, whereas men reported exercising for enjoyment more than women. Reasons for exercise predicted quality of life for women over exercise. For men, exercise was the best predictor of quality of life. Ultimately, exercise is not beneficial for a woman's quality of life under all conditions. PMID- 27668244 TI - Pancreatic DCLK1 marks quiescent but oncogenic progenitors: a possible link to neuroendocrine tumors. PMID- 27668245 TI - Wnt signalling meets epigenetics. PMID- 27668246 TI - From stem cells to comparative corticogenesis: a bridge too far? AB - It has been hypothesized that the higher number of neurons in human cortex compared to the chimpanzee and other primate species is key to high cognitive function. Are human cortical precursors endowed with specific properties that drive greater neuronal expansion than in other non-human primates? Otani et al. 2016 addressed this issue taking advantage of comparative in vitro corticogenesis models based on human, chimpanzee and macaque pluripotent stem cells. Clonal analysis revealed a heterochrony of early developmental events possibly leading to a relatively higher expansion of human cortical precursor population. In absence of evidence going beyond putative correlation, the claim that stem cell models of cortical development indicate mechanism of cortical size regulation needs to be further examined notably with respect to in vivo observations of cortical precursor lineages. PMID- 27668247 TI - Shedding light on HSC dormancy-a role for the DARC. PMID- 27668248 TI - Switching on regeneration. PMID- 27668249 TI - A role for miR-34 in colon cancer stem cell homeostasis. PMID- 27668250 TI - Aging vs. rejuvenation: reprogramming to iPSCs does not turn back the clock for somatic mitochondrial DNA mutations. PMID- 27668251 TI - The DARC-CD82 axis discloses bone marrow macrophages as guardians of long-term hematopoietic stem cells quiescence. PMID- 27668252 TI - Intercondylar Route of Prosthetic Infragenicular Femoropopliteal Bypass Has Better Primary, Assisted, and Secondary Patency but Not Limb Salvage Rate Compared to the Medial Route. AB - Aim. To compare the differences between medial and intercondylar infragenicular femoropopliteal prosthetic bypasses in terms of their midterm patency and limb salvage rates. Methods. Ninety-three consecutive patients with peripheral arterial disease who underwent a simple distal femoropopliteal bypass using a reinforced polytetrafluorethylene graft were included in this retrospective study. The bypass was constructed in the intercondylar route in 52 of the patients (group A) and in 41 in the medial route (group B). Results. Median observation time of the patients was 12.7 (IQR 4.6-18.5) months. There were 22 and 24 interventional or surgical procedures (angioplasty, stenting, thrombolysis, thrombectomy, or correction of the anastomosis) performed to restore patency of the reconstruction in groups A and B, respectively (p = 0.14). The 20-month primary, assisted, and secondary patency rates and limb salvage rates were 57%, 57%, 81%, and 80% in group A compared to 21%, 23%, 55%, and 82% in group B (p = 0.0012, 0.0052, 0.022, and 0.44, resp.). Conclusion. Despite better primary, assisted, and secondary patency rates in patients with a prosthetic infragenicular femoropopliteal bypass embedded in the intercondylar fossa compared to patients with the medial approach, there is no benefit in terms of the limb salvage rate and the number of interventions required to maintain patency of the reconstruction. PMID- 27668253 TI - Enzymatic Synthesis of Sorboyl-Polydatin Prodrug in Biomass-Derived 2 Methyltetrahydrofuran and Antiradical Activity of the Unsaturated Acylated Derivatives. AB - Efficient and highly regioselective synthesis of the potential 6''-O-sorboyl polydatin prodrug in biomass-derived 2-methyltetrahydrofuran (2-MeTHF) was achieved using Candida antarctica lipase B for the first time. Under the optimal conditions, the initial reaction rate, maximum substrate conversion, and 6'' regioselectivity were as high as 8.65 mM/h, 100%, and 100%, respectively. Kinetic and operational stability investigations evidently demonstrated excellent enzyme compatibility of the 2-MeTHF compared to the traditional organic solvents. With respect to the antioxidant properties, three unsaturated ester derivatives showed slightly lower DPPH radical scavenging activities than the parent agent. Interestingly, further studies also revealed that the antiradical capacities of the acylates decreased with the elongation of the unsaturated aliphatic chain length from C4 to C11. The reason might be attributed to the increased steric hindrance derived from the acyl residues in derivatives. PMID- 27668255 TI - Obstacles and Enablers on the Way towards Integrated Physical Activity Policies for Childhood Obesity Prevention: An Exploration of Local Policy Officials' Views. AB - Background. Limited physical activity (PA) is a risk factor for childhood obesity. In Netherlands, as in many other countries worldwide, local policy officials bear responsibility for integrated PA policies, involving both health and nonhealth domains. In practice, its development seems hampered. We explore which obstacles local policy officials perceive in their effort. Methods. Fifteen semistructured interviews were held with policy officials from health and nonhealth policy domains, working at strategic, tactic, and operational level, in three relatively large municipalities. Questions focused on exploring perceived barriers for integrated PA policies. The interviews were deductively coded by applying the Behavior Change Ball framework. Findings. Childhood obesity prevention appeared on the governmental agenda and all officials understood the multicausal nature. However, operational officials had not yet developed a tradition to develop integrated PA policies due to insufficient boundary-spanning skills and structural and cultural differences between the domains. Tactical level officials did not sufficiently support intersectoral collaboration and strategic level officials mainly focused on public-private partnerships. Conclusion. Developing integrated PA policies is a bottom-up innovation process that needs to be supported by governmental leaders through better guiding organizational processes leading to such policies. Operational level officials can assist in this by making progress in intersectoral collaboration visible. PMID- 27668254 TI - A Systematised Review of Primary School Whole Class Child Obesity Interventions: Effectiveness, Characteristics, and Strategies. AB - Background. A systematised review was conducted to examine the effectiveness of school-based interventions that focus on changing dietary intake and physical activity levels to reduce childhood obesity. Methods. Multiple databases were searched for randomised and nonrandomised interventions from 2007 to 2016 in full time elementary schools, which were delivered to the whole class, included dietary and physical activity components, involved both sexes, were written in English, and used body mass index (BMI) as an outcome. Results. The database search produced 8,866 titles from which 78 were deemed relevant and assessed for inclusion resulting in 15 studies meeting all inclusion criteria. From these 15 studies, 9 yielded a reduction or stabilisation in BMI or BMI z-score in the entire intervention group and/or subgroups. Programmes lasting between 6 and 12 months that involve multiple environmental, educational, and physical strategies appear to be most likely to result in BMI or BMI z-score improvement. Moderators most likely influencing an improvement in BMI included increased physical activity, decreased sugar sweetened beverages intake, and increased fruit intake. Conclusions. School-based interventions may be an effective means for child obesity prevention. The identification of consistent elements used in school based interventions that have demonstrated effectiveness may aid in preventing child obesity. PMID- 27668257 TI - Evaluation of Smartphone Applications for Cardiopulmonary Resuscitation Training in South Korea. AB - Objective. There are many smartphone-based applications (apps) for cardiopulmonary resuscitation (CPR) training. We investigated the conformity and the learnability/usability of these apps for CPR training and real-life supports. Methods. We conducted a mixed-method, sequential explanatory study to assess CPR training apps downloaded on two apps stores in South Korea. Apps were collected with inclusion criteria as follows, Korean-language instruction, training features, and emergency supports for real-life incidents, and analyzed with two tests; 15 medical experts evaluated the apps' contents according to current Basic Life Support guidelines in conformity test, and 15 nonmedical individuals examined the apps using System Usability Scale (SUS) in the learnability/usability test. Results. Out of 79 selected apps, five apps were included and analyzed. For conformity (ICC, 0.95, p < 0.001), means of all apps were greater than 12 of 20 points, indicating that they were well designed according to current guidelines. Three of the five apps yielded acceptable level (greater than 68 of 100 points) for learnability/usability. Conclusion. All the included apps followed current BLS guidelines and a majority offered acceptable learnability/usability for layperson. Current and developmental smartphone-based CPR training apps should include accurate CPR information and be easy to use for laypersons that are potential rescuers in real-life incidents. For Clinical Trials. This is a clinical trial, registered at the Clinical Research Information Service (CRIS, cris.nih.go.kr), number KCT0001840. PMID- 27668256 TI - Evaluation of Influenza Vaccination Efficacy: A Universal Epidemic Model. AB - By means of a designed epidemic model, we evaluated the influence of seasonal vaccination coverage as well as a potential universal vaccine with differing efficacy on the aftermath of seasonal and pandemic influenza. The results of the modeling enabled us to conclude that, to control a seasonal influenza epidemic with a reproduction coefficient R0 <= 1.5, a 35% vaccination coverage with the current seasonal influenza vaccine formulation is sufficient, provided that other epidemiology measures are regularly implemented. Increasing R0 level of pandemic strains will obviously require stronger intervention. In addition, seasonal influenza vaccines fail to confer protection against antigenically distinct pandemic influenza strains. Therefore, the necessity of a universal influenza vaccine is clear. The model predicts that a potential universal vaccine will be able to provide sufficient reliable (90%) protection against pandemic influenza only if its efficacy is comparable with the effectiveness of modern vaccines against seasonal influenza strains (70%-80%); given that at least 40% of the population has been vaccinated in advance, ill individuals have been isolated (observed), and a quarantine has been introduced. If other antiepidemic measures are absent, a vaccination coverage of at least 80% is required. PMID- 27668258 TI - The Accuracy of Broselow Tape Weight Estimate among Pediatric Population. AB - Objective. To determine the accuracy of the Broselow Tape (BT) versions 2007 and 2011 in estimating weight among pediatric population. Methods. A cross-sectional study was conducted at King Fahad Medical City and six schools across Riyadh province on 1-143-month-old children. BT 2007 and 2011 estimated weights were recorded. Both tapes via the child's height produce an estimated weight, which was compared with the actual weight. Results. A total of 3537 children were recruited. The height (cm) of the subjects was 97.7 +/- 24.1 and the actual weight (kg) was 16.07 +/- 8.9, whereas the estimated weight determined by BT 2007 was 15.87 +/- 7.56 and by BT 2011 was 16.38 +/- 7.95. Across all the five age groups, correlation between actual weight and BT 2007 ranged between 0.702 and 0.788, while correlation between actual weight and BT 2011 ranged between 0.698 and 0.788. Correlation between BT 2007 and BT 2011 across all the five age groups ranged from 0.979 to 0.989. Accuracy of both the tape versions was adversely affected when age was >95 months and body weight was >26 kilograms. Conclusions. Our study showed that BT 2007 and 2011 provided accurate estimation of the body weight based on measured body height. However, 2011 version provided more precise estimate for weight. PMID- 27668259 TI - Complex Approach to Conceptual Design of Machine Mechanically Extracting Oil from Jatropha curcas L. Seeds for Biomass-Based Fuel Production. AB - One of important sources of biomass-based fuel is Jatropha curcas L. Great attention is paid to the biofuel produced from the oil extracted from the Jatropha curcas L. seeds. A mechanised extraction is the most efficient and feasible method for oil extraction for small-scale farmers but there is a need to extract oil in more efficient manner which would increase the labour productivity, decrease production costs, and increase benefits of small-scale farmers. On the other hand innovators should be aware that further machines development is possible only when applying the systematic approach and design methodology in all stages of engineering design. Systematic approach in this case means that designers and development engineers rigorously apply scientific knowledge, integrate different constraints and user priorities, carefully plan product and activities, and systematically solve technical problems. This paper therefore deals with the complex approach to design specification determining that can bring new innovative concepts to design of mechanical machines for oil extraction. The presented case study as the main part of the paper is focused on new concept of screw of machine mechanically extracting oil from Jatropha curcas L. seeds. PMID- 27668260 TI - Natural Language Processing Based Instrument for Classification of Free Text Medical Records. AB - According to the Ministry of Labor, Health and Social Affairs of Georgia a new health management system has to be introduced in the nearest future. In this context arises the problem of structuring and classifying documents containing all the history of medical services provided. The present work introduces the instrument for classification of medical records based on the Georgian language. It is the first attempt of such classification of the Georgian language based medical records. On the whole 24.855 examination records have been studied. The documents were classified into three main groups (ultrasonography, endoscopy, and X-ray) and 13 subgroups using two well-known methods: Support Vector Machine (SVM) and K-Nearest Neighbor (KNN). The results obtained demonstrated that both machine learning methods performed successfully, with a little supremacy of SVM. In the process of classification a "shrink" method, based on features selection, was introduced and applied. At the first stage of classification the results of the "shrink" case were better; however, on the second stage of classification into subclasses 23% of all documents could not be linked to only one definite individual subclass (liver or binary system) due to common features characterizing these subclasses. The overall results of the study were successful. PMID- 27668261 TI - Optimising Health Literacy and Access of Service Provision to Community Dwelling Older People with Diabetes Receiving Home Nursing Support. AB - Background. Health literacy is the ability to access, understand, and use information and services for good health. Among people with chronic conditions, health literacy requirements for effective self-management are high. The Optimising Health Literacy and Access (Ophelia) study engaged diverse organisations in the codesign of interventions involving the Health Literacy Questionnaire (HLQ) needs assessment, followed by development and evaluation of interventions addressing identified needs. This study reports the process and outcomes of one of the nine organisations, the Royal District Nursing Service (RDNS). Methods. Participants were home nursing clients with diabetes. The intervention included tailored diabetes self-management education according to preferred learning style, a standardised diabetes education tool, resources, and teach-back method. Results. Needs analysis of 113 quota-sampled clients showed difficulties managing health and finding and appraising health information. The service-wide diabetes education intervention was applied to 24 clients. The intervention was well received by clients and nurses. Positive impacts on clients' diabetes knowledge and behaviour were seen and nurses reported clear benefits to their practice. Conclusion. A structured method that supports healthcare services to codesign interventions that respond to the health literacy needs of their clients can lead to evidence-informed, sustainable practice changes that support clients to better understand effective diabetes self management. PMID- 27668263 TI - ESammon: A Computationaly Enhanced Sammon Mapping based on Data Density. AB - Sammon mapping is a widely used visualization technique to display complex data from high- to low-dimensional space. However, its extensive computational cost may pose potential computational challenges to big data visualization. This paper proposes a computationally-enhanced Sammon mapping (ESammon) by leveraging the characteristics of spatial data density. Unlike the conventional Sammon, ESammon preserves critical pairwise distances between data points in the process of projection, instead of all distances. Specifically, we integrated the Directed Acyclic-Graph (DAG) based data density characterization method to select the critical distances. The numerical results demonstrated that our ESammon can achieve comparable projection results as the conventional Sammon mapping while reducing the computational cost from O(N2) toO(N). PMID- 27668262 TI - Association between Serum Cystatin C and Diabetic Foot Ulceration in Patients with Type 2 Diabetes: A Cross-Sectional Study. AB - Serum cystatin C (CysC) has been identified as a possible potential biomarker in a variety of diabetic complications, including diabetic peripheral neuropathy and peripheral artery disease. We aimed to examine the association between CysC and diabetic foot ulceration (DFU) in patients with type 2 diabetes (T2D). 411 patients with T2D were enrolled in this cross-sectional study at a university hospital. Clinical manifestations and biochemical parameters were compared between DFU group and non-DFU group. The association between serum CysC and DFU was explored by binary logistic regression analysis. The cut point of CysC for DFU was also evaluated by receiver operating characteristic (ROC) curve. The prevalence of coronary artery disease, diabetic nephropathy (DN), and DFU dramatically increased with CysC (P < 0.01) in CysC quartiles. Multivariate logistic regression analysis indicated that the significant risk factors for DFU were serum CysC, coronary artery disease, hypertension, insulin use, the differences between supine and sitting TcPO2, and hypertension. ROC curve analysis revealed that the cut point of CysC for DFU was 0.735 mg/L. Serum CysC levels correlated with DFU and severity of tissue loss. Our study results indicated that serum CysC was associated with a high prevalence of DFU in Chinese T2D subjects. PMID- 27668264 TI - Effect of WIC Food Package Changes on Dietary Intake of Preschool Children in New Mexico. AB - OBJECTIVES: This study examined WIC policy change effects on dietary intake of preschool children from WIC-participating households in rural New Mexico communities. METHODS: Dietary intake of children enrolled in Head Start in 8 communities was compared before and after 2009 WIC food package changes. RESULTS: Following the policy change, participants reported significantly increased consumption of lower-fat milk, reduced consumption of saturated fat (grams), and decreased consumption of vegetables without potatoes. No significant differences in fruit, fruit juice, vegetables including potatoes, whole-grains and saturated fat (percent-energy) consumption were observed. CONCLUSIONS: WIC policy changes have the potential to improve children's saturated fat intake. More research with robust designs is necessary to examine long-term effects of WIC policy changes. PMID- 27668265 TI - A General Framework for Considering Selection Bias in EHR-Based Studies: What Data Are Observed and Why? AB - Electronic health records (EHR) data are increasingly seen as a resource for cost effective comparative effectiveness research (CER). Since EHR data are collected primarily for clinical and/or billing purposes, their use for CER requires consideration of numerous methodologic challenges including the potential for confounding bias, due to a lack of randomization, and for selection bias, due to missing data. In contrast to the recent literature on confounding bias in EHR based CER, virtually no attention has been paid to selection bias possibly due to the belief that standard methods for missing data can be readily-applied. Such methods, however, hinge on an overly simplistic view of the available/missing EHR data, so that their application in the EHR setting will often fail to completely control selection bias. Motivated by challenges we face in an on-going EHR-based comparative effectiveness study of choice of antidepressant treatment and long term weight change, we propose a new general framework for selection bias in EHR based CER. Crucially, the framework provides structure within which researchers can consider the complex interplay between numerous decisions, made by patients and health care providers, which give rise to health-related information being recorded in the EHR system, as well as the wide variability across EHR systems themselves. This, in turn, provides structure within which: (i) the transparency of assumptions regarding missing data can be enhanced, (ii) factors relevant to each decision can be elicited, and (iii) statistical methods can be better aligned with the complexity of the data. PMID- 27668266 TI - An Automated Method for Identifying Individuals with a Lung Nodule Can Be Feasibly Implemented Across Health Systems. AB - INTRODUCTION: The incidence of incidentally detected lung nodules is rapidly rising, but little is known about their management or associated patient outcomes. One barrier to studying lung nodule care is the inability to efficiently and reliably identify the cohort of interest (i.e. cases). Investigators at Kaiser Permanente Southern California (KPSC) recently developed an automated method to identify individuals with an incidentally discovered lung nodule, but the feasibility of implementing this method across other health systems is unknown. METHODS: A random sample of Group Health (GH) members who had a computed tomography in 2012 underwent chart review to determine if a lung nodule was documented in the radiology report. A previously developed natural language processing (NLP) algorithm was implemented at our site using only knowledge of the key words, qualifiers, excluding terms, and the logic linking these parameters. RESULTS: Among 499 subjects, 156 (31%, 95% confidence interval [CI] 27-36%) had an incidentally detected lung nodule. NLP identified 189 (38%, 95% CI 33-42%) individuals with a nodule. The accuracy of NLP at GH was similar to its accuracy at KPSC: sensitivity 90% (95% CI 85-95%) and specificity 86% (95% CI 82-89%) versus sensitivity 96% (95% CI 88-100%) and specificity 86% (95% CI 75 94%). CONCLUSION: Automated methods designed to identify individuals with an incidentally detected lung nodule can feasibly and independently be implemented across health systems. Use of these methods will likely facilitate the efficient conduct of multi-site studies evaluating practice patterns and associated outcomes. PMID- 27668267 TI - DOXIL when combined with Withaferin A (WFA) targets ALDH1 positive cancer stem cells in ovarian cancer. AB - Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity. Resistance to chemotherapy and recurrence of cancer is primarily attributed to the presence of cancer stem cells (CSCs), a small population of cells present in cancer. Effect of DOXIL and withaferin A (WFA), both alone and in combination, was investigated on cell proliferation of ovarian cancer cell line A2780 and tumor growth in SCID mice bearing i.p. ovarian tumors. ALDH1 cells were isolated from A2780 using cell sorter, and effect of DOXIL and WFA both alone and in combination on tumorigenic function of ALDH1 was studied using spheroids formation assays in vitro. Western blots were performed to examine the expression of ALDH1 and Notch 1 genes. In our studies, we showed, for the first time, that DOXIL when combined with withaferin A (WFA) elicits synergistic effect on inhibition of cell proliferation of ovarian cancer cells and inhibits the expression of ALDH1 protein, a marker for ALDH1 positive cancer stem cells (CSCs), and Notch1, a signaling pathway gene required for self-renewal of CSCs. Inhibition of expression of both ALDH1 and Notch1 genes by WFA was found to be dose dependent, whereas DOXIL (200 nM) was found to be ineffective. SCID mice, bearing i.p. ovarian tumors, were treated with a small dose of DOXIL (2 mg/kg) in combination with a sub-optimal dose of WFA (2 mg/kg) which resulted in a highly significant (60% to 70%) reduction in tumor growth, and complete inhibition of metastasis compared to control. In contrast, WFA treatment showed a significant reduction in tumor growth but no change in metastasis compared to control. DOXIL showed non-significant reduction in tumor growth and no change in metastasis compared to control. Isolated ALDH1 positive CSCs treated with the combination of DOXIL and WFA resulted in a significant reduction in spheroids formation (tumorigenic function of CSCs) and expression of ALDH1 protein. WFA when used alone at a concentration of 1.5 MUM was found to be highly effective in suppression of ALDH1 expression, whereas DOXIL at a concentration of 200 nM was found to be ineffective. DOXIL in combination with WFA elicits synergistic effects, targets cancer stem cells, and has potential to minimize induction of drug resistance and reoccurrence of cancer. Based on our studies, we conclude that the combination of DOXIL with WFA has the potential to be an effective therapy for ovarian cancer and may ameliorate DOXIL related side effects as well as recurrence of ovarian cancer leading to increase in patients' survival rate. PMID- 27668268 TI - Lenalidomide Polarizes Th1-specific Anti-tumor Immune Response and Expands XBP1 Antigen-Specific Central Memory CD3+CD8+ T cells against Various Solid Tumors. AB - INTRODUCTION: Effective combination immunotherapeutic strategies may be required to enhance effector cells' anti-tumor activities and improve clinical outcomes. METHODS: XBP1 antigen-specific cytotoxic T lymphocytes (XBP1-CTL) generated using immunogenic heteroclitic XBP1 US184-192 (YISPWILAV) and XBP1 SP367-375 (YLFPQLISV) peptides or various solid tumor cells over-expressing XBP1 target antigen were evaluated, either alone or in combination with lenalidomide, for phenotype and immune functional activity. RESULTS: Lenalidomide treatment of XBP1 CTL increased the proportion of CD45RO+ memory CD3+CD8+ T cells, but not the total CD3+CD8+ T cells. Lenalidomide upregulated critical T cell activation markers and costimulatory molecules (CD28, CD38, CD40L, CD69, ICOS), especially within the central memory CTL subset of XBP1-CTL, while decreasing TCRalphabeta and T cell checkpoint blockade (CTLA-4, PD-1). Lenalidomide increased the anti tumor activities of XBP1-CTL memory subsets, which were associated with expression of Th1 transcriptional regulators (T-bet, Eomes) and Akt activation, thereby resulting in enhanced IFN-gamma production, granzyme B upregulation and specific CD28/CD38-positive and CTLA-4/PD-1-negative cell proliferation. CONCLUSIONS: These studies suggest the potential benefit of lenalidomide treatment to boost anti-tumor activities of XBP1-specific CTL against a variety of solid tumors and enhance response to an XBP1-directing cancer vaccine regime. PMID- 27668269 TI - FACS-based Satellite Cell Isolation From Mouse Hind Limb Muscles. AB - Fluorescence Activated Cell Sorting (FACS) is a sensitive and accurate method for purifying satellite cells, or muscle stem cells, from adult mouse skeletal muscle (Liu et al., 2013; Sacco et al., 2008; Tierney et al., 2014). Mechanical and enzymatic digestion of hind limb muscles releases mononuclear muscle cells into suspension. This protocol employs fractionation strategies to deplete cells expressing the cell surface markers CD45, CD31, CD11b and Ly-6A/E-Sca1, both by magnetic separation and FACS-based exclusion, and positively select for cells expressing a7-integrin and CD34. This enables the researcher to successfully enrich satellite cells that uniformly express the paired-box transcription factor Pax7 and are capable of long-term self-renewal, skeletal muscle repair and muscle stem cell pool repopulation. PMID- 27668270 TI - Eye Tracking Outcomes in Tobacco Control Regulation and Communication: A Systematic Review. AB - OBJECTIVE: In this paper we synthesize the evidence from eye tracking research in tobacco control to inform tobacco regulatory strategies and tobacco communication campaigns. METHODS: We systematically searched 11 databases for studies that reported eye tracking outcomes in regards to tobacco regulation and communication. Two coders independently reviewed studies for inclusion and abstracted study characteristics and findings. RESULTS: Eighteen studies met full criteria for inclusion. Eye tracking studies on health warnings consistently showed these warnings often were ignored, though eye tracking demonstrated that novel warnings, graphic warnings, and plain packaging can increase attention toward warnings. Eye tracking also revealed that greater visual attention to warnings on advertisements and packages consistently was associated with cognitive processing as measured by warning recall. CONCLUSIONS: Eye tracking is a valid indicator of attention, cognitive processing, and memory. The use of this technology in tobacco control research complements existing methods in tobacco regulatory and communication science; it also can be used to examine the effects of health warnings and other tobacco product communications on consumer behavior in experimental settings prior to the implementation of novel health communication policies. However, the utility of eye tracking will be enhanced by the standardization of methodology and reporting metrics. PMID- 27668271 TI - Respiratory Complications Due to Sulfur Mustard Exposure. AB - Sulfur mustard (SM) or bis (2-chloroethyl) sulfide is a vesicant and alkylating chemical weapon. SM was used in the 1980s against Iran by Iraqi forces. After exposure to SM in initial acute phase the greatest damage is incurred by the eyes, skin and lungs and the highest damage is caused to the lungs. This injury not only in the acute phase but also in the long-term has the highest prevalence among these patients. Clinical symptoms of people after exposure to SM start with irritation of the nose and sinuses in the mild doses to the runny nose and pain at higher doses and even irritation of the airways and bronchial engagement in very high doses. Respiratory complications in patients exposed to SM have been associated with long-term symptoms and these symptoms add to the intensity of the complication. Bloody sputum, feeling of tightness in the chest and shortness of breath over nights are among common symptoms; also the main respiratory symptoms including generalized wheezing, rale (crackle), decreased breath sounds and cyanosis and Apparently FEV1 is reduced by 50 mL/year. In these patients there are changes in blood cells especially in white blood cells and neutrophils and systemic inflammation and systemic changes with other comorbidities are observed. Although SM pulmonary patients' treatment is based on bronchodilators and long acting-beta2 agonists, paying attention to the comorbidities with prior systemic changes in these patients is a reason for the need to change treatment strategies of these patients with systemic and extra-pulmonary therapy. PMID- 27668272 TI - Data on serologic inflammatory biomarkers assessed using multiplex assays and host characteristics in the Multicenter AIDS Cohort Study (MACS). AB - This article contains data on the associations between fixed and modifiable host characteristics and twenty-three biomarkers of inflammation and immune activation measured longitudinally in a cohort of 250 HIV-uninfected men from the Multicenter AIDS Cohort Study (1984-2009) after adjusting for age, study site, and blood draw time of day using generalized gamma regression. This article also presents associations between each biomarker and each host characteristic in a sample restricted to 2001-2009. These data are supplemental to our original research article entitled "Host factors associated with serologic inflammatory markers assessed using multiplex assays" (McKay, S. Heather, Bream, H. Jay, Margolick, B. Joseph, Martinez-Maza, Otoniel, Phair, P. John, Rinaldo, R. Charles, Abraham, G. Alison, L.P. Jacobson, 2016) [1]. PMID- 27668273 TI - Diffusion tensor microscopy data (15.6 MUm in-plane) of white matter tracts in the human, pig, and rat spinal cord with corresponding tissue histology. AB - The following article contains nine diffusion tensor imaging (DTI) datasets acquired with magnetic resonance microscopy (MRM, 15.6 MUm in-plane). All data was collected in the region bordering the ventral horn and white matter of cross sections from the spinal cord enlargements along with each sample's corresponding tissue histology. These data are collected in fixed spinal cord sections of varying thicknesses taken from rat (2*21 direction DTI datasets), pig (1*21 direction DTI dataset), and human (5*21 direction DTI datasets + 1*6 direction DTI dataset) tissue sources. Following MRM acquisition, the sections were histologically processed using Nissl or Black-Gold II (Histo-Chem Inc., 1BGII) myelin stain and imaged again using light microscopy techniques. Methodological procedures are an amalgamation of protocol components described previously (doi:10.1016/j.neuroimage.2010.04.031 [1], doi:10.1016/j.neuroimage.2011.04.052 [2]). PMID- 27668274 TI - Behavioral and cognitive data in mice with different tryptophan-metabolizing enzymes knocked out. AB - This article demonstrates behavioral changes in mice in response to free adaptation and drinking session adaptation modules implemented in their social home environment, the IntelliCage. These data complement the study "Deletion of TDO2, IDO-1 and IDO-2 differentially affects mouse behavior and cognitive function" (Too LK, Li KM, Suarna C, Maghzal GJ, Stocker R, McGregor IS, et al., 2016) [1]. Prior to programmed drinking sessions, all mice were exposed to a home cage adaptation module during which there was no time limit on water access - the free adaptation module. The exploratory behaviors are here expressed as percentages of visits with nosepokes and of visits with licks. The measurements by percentage of exploratory activity showed minimal genotype effects. The number of nosepokes or licks per corner visit also was compared between WT and gene knockout (GKO) IDO1 mice, WT and GKO IDO2 mice and WT and GKO TDO2 mice and demonstrated unremarkable behavioral changes during the free adaptation module. Analysis of drinking session adaptation behavior showed no genotype effect between WT and GKO of IDO1, IDO2 or TDO2 background. Notwithstanding the absence of genotype differences, each IDO1, IDO2 or TDO2 animal group displayed a specific pattern of adaptation to the drinking session modules. Furthermore, IDO1 GKO mice showed a more rapid recovery of lick frequency to the baseline level compared to the WT equivalents in a simple patrolling task during the first complete testing cycle (R1). TDO2 GKO mice on the other hand did not differ from their WT equivalents in terms of lick frequency over the three test days of complex patrolling and discrimination reversal tasks. Lastly, IDO2 GKO mice reduced their visits to the permanently non-rewarding reference corners by the same degree as did the WT mice. PMID- 27668275 TI - Pgu-Face: A dataset of partially covered facial images. AB - In this article we introduce a human face image dataset. Images were taken in close to real-world conditions using several cameras, often mobile phone's cameras. The dataset contains 224 subjects imaged under four different figures (a nearly clean-shaven countenance, a nearly clean-shaven countenance with sunglasses, an unshaven or stubble face countenance, an unshaven or stubble face countenance with sunglasses) in up to two recording sessions. Existence of partially covered face images in this dataset could reveal the robustness and efficiency of several facial image processing algorithms. In this work we present the dataset and explain the recording method. PMID- 27668276 TI - Data from computational analysis of the peptide linkers in the MocR bacterial transcriptional regulators. AB - Detailed data from statistical analyses of the structural properties of the inter domain linker peptides of the bacterial regulators of the family MocR are herein reported. MocR regulators are a recently discovered subfamily of bacterial regulators possessing an N-terminal domain, 60 residue long on average, folded as the winged-helix-turn-helix architecture responsible for DNA recognition and binding, and a large C-terminal domain (350 residue on average) that belongs to the fold type-I pyridoxal 5'-phosphate (PLP) dependent enzymes such aspartate aminotransferase. Data show the distribution of several structural characteristics of the linkers taken from bacterial species from five different phyla, namely Actinobacteria, Alpha-, Beta-, Gammaproteobacteria and Firmicutes. Interpretation and discussion of reported data refer to the article "Structural properties of the linkers connecting the N- and C- terminal domains in the MocR bacterial transcriptional regulators" (T. Milano, S. Angelaccio, A. Tramonti, M. L. Di Salvo, R. Contestabile, S. Pascarella, 2016) [1]. PMID- 27668277 TI - Data set for transcriptome analysis of Escherichia coli exposed to nickel. AB - Ni is recognized as an element that is toxic to humans, acting as an allergen and a carcinogenic agent, and it is also toxic to plants. The toxicity of Ni has been understudied in microorganisms. The data presented here were obtained by submitting the model bacterium Escherichia coli K-12 to nickel stress. To identify expressed genes, RNA-Seq was performed. Bacteria were exposed to 50 uM NiCl2 during 10 min. Exposure to Ni lead to the deregulation of 57% of the E. coli transcripts. Further analysis using DAVID identified most affected biological pathways. The list of differentially expressed genes and physiological consequences of Ni stress are described in "Ni exposure impacts the pool of free Fe and modifies DNA supercoiling via metal-induced oxidative stress in Escherichia coli K-12" (M. Gault, G. Effantin, A. Rodrigue, 2016) [1]. PMID- 27668278 TI - Data on combination effect of PEG-coated gold nanoparticles and non-thermal plasma inhibit growth of solid tumors. AB - Highly resistant tumor cells are hard to treat at low doses of plasma. Therefore, researchers have gained more attention to development of enhancers for plasma therapy. Some enhancers could improve the efficacy of plasma towards selectivity of cancer cells damage. In this dataset, we report the application of low doses of PEG-coated gold nanoparticles with addition of plasma treatment. This data consists of the effect of PEG-coated GNP and cold plasma on two solid tumor cell lines T98G glioblastoma and A549 lung adenocarcinoma. Cell proliferation, frequency of cancer stem cell population studies by this co-treatment was reported. Finally, we included in this dataset the effect of co-treatment in vivo, using tumor xenograft nude mice models. The data supplied in this article supports the accompanying publication "Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT" (N. K. Kaushik, N. Kaushik, K. C. Yoo, N Uddin, J. S. Kim, S. J. Lee et al., 2016) [1]. PMID- 27668280 TI - Punica granatum L. (Pomegranate) Extract: In Vivo Study of Antimicrobial Activity against Porphyromonas gingivalis in Galleria mellonella Model. AB - Due to the increase of bacterial resistance, medicinal alternatives are being explored. Punica granatum L. is an effective herbal extract with broad spectrum of action and bactericidal, antifungal, anthelmintic potential and being able to modulate the immune response. The aim was to evaluate the antimicrobial activity of pomegranate glycolic extract (PGE) against the periodontal pathogen Porphyromonas gingivalis by using Galleria mellonella as in vivo model. Fifteen larvae were used per group. Injection of high concentration (200, 100, and 25 mg/mL) of PGE showed a toxic effect, leading them to death. A suspension of P. gingivalis (106 cells/mL) was inoculated in the left last proleg and PGE (12.5, 6.25, 3.1, and 2.5 mg/mL) were injected into the right proleg. The larvae were then kept at 37 degrees C under the dark. Injection of PGE at any dose statistically improved larvae survival rates. The data were analysed (log-rank test, Mantel-Cox, P < 0.05) and showed that all concentrations of PGE (12.5, 6.25, 3.1, and 2.5 mg/mL) presented higher larval survival rates, with significant statistical difference in relation to control group (P. gingivalis). In conclusion, the PGE had antimicrobial action against P. gingivalis in vivo model using G. mellonella. PMID- 27668279 TI - Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study. AB - In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES. PMID- 27668281 TI - Molecular Identification and Traceability of Illegal Trading in Lignobrycon myersi (Teleostei: Characiformes), a Threatened Brazilian Fish Species, Using DNA Barcode. AB - Lignobrycon myersi is a threatened freshwater fish species and endemic of a few coastal rivers in northeastern Brazil. Even though the Brazilian laws prohibit the fisheries of threatened species, L. myersi is occasionally found in street markets, being highly appreciated by local population. In order to provide a reliable DNA barcode dataset for L. myersi, we compared mitochondrial sequences of cytochrome c oxidase subunit I (COI) from fresh, frozen, and salt-preserved specimens. Phylogenetically related species (Triportheus spp.) and other fish species (Astyanax fasciatus) commonly mixed with L. myersi in street markets were also included to test the efficiency of molecular identification. In spite of the differences in conservation processes and advanced deterioration of some commercial samples, high-quality COI sequences were obtained and effective in discriminating L. myersi specimens. In addition, while populations from Contas and Almada River basins seem to comprise a single evolutionary lineage, the specimens from Cachoeira River were genetically differentiated, indicating population structuring. Therefore, DNA barcoding has proved to be useful to trace the illegal trading of L. myersi and to manage threatened populations, which should focus on conservation of distinct genetic stocks and mitigation on human impacts along their range. PMID- 27668282 TI - ABCC6 Out From the Cold: Identification of the ABCC6 Substrate as a Therapy for Pseudoxanthoma Elasticum and Cardiovascular Disease. PMID- 27668283 TI - Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD. AB - OBJECTIVE: To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD). METHODS: Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing. RESULTS: We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype. CONCLUSIONS: A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early onset dementia with prominent frontal lobe and motor symptoms. PMID- 27668284 TI - Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability. AB - Recently, exome sequencing has extended our knowledge of genetic causes of developmental delay through identification of de novo, germline mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) in 13 patients with neurodevelopmental disability and a wide range of additional symptoms and signs including hypotonia in 11 and seizures in 10 of the patients. Limb/arm dystonia was found in 2 patients.(1). PMID- 27668285 TI - Thermogenic profiling using magnetic resonance imaging of dermal and other adipose tissues. AB - Dermal white adipose tissue (dWAT) was recently recognized for its potential to modify whole body metabolism. Here, we show that dWAT can be quantified using a high-resolution, fat-specific magnetic resonance imaging (MRI) technique. Noninvasive MRI has been used to describe adipocyte depots for many years; the MRI technique we describe uses an advanced fat-specific method to measure the thickness of dWAT, together with the total volume of WAT and the relative activation/fat depletion of brown adipose tissues (BAT). Since skin-embedded adipocytes may provide natural insulation, they provide an important counterpoint to the activation of thermogenic brown and beige adipose tissues, whereby these distinct depots are functionally interrelated and require simultaneous assay. This method was validated using characterized mouse cohorts of a lipodystrophic, dWAT-deficient strain (syndecan-1 KO) and 2 obese models (diet-induced obese mice and genetically obese animals, ob/ob). Using a preliminary cohort of normal human subjects, we found the thickness of skin-associated fat varied 8-fold, from 0.13 1.10 cm; on average, this depot is calculated to weigh 8.8 kg. PMID- 27668286 TI - Characterization of candidate genes in inflammatory bowel disease-associated risk loci. AB - GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn's disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or dependent manner. We demonstrate that on average approximately 60% of disease associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis. PMID- 27668287 TI - Enhanced protective antibody to a mutant meningococcal factor H-binding protein with low-factor H binding. AB - Meningococcal factor H-binding protein (FHbp) is an antigen in 2 serogroup B meningococcal vaccines. FHbp specifically binds human and some nonhuman primate complement FH. To investigate the effect of binding of FH to FHbp on protective antibody responses, we immunized infant rhesus macaques with either a control recombinant FHbp antigen that bound macaque FH or a mutant antigen with 2 amino acid substitutions and >250-fold lower affinity for FH. The mutant antigen elicited 3-fold higher serum IgG anti-FHbp titers and up to 15-fold higher serum bactericidal titers than the control FHbp vaccine. When comparing sera with similar IgG anti-FHbp titers, the antibodies elicited by the mutant antigen gave greater deposition of complement component C4b on live meningococci (classical complement pathway) and inhibited binding of FH, while the anti-FHbp antibodies elicited by the control vaccine enhanced FH binding. Thus, the mutant FHbp vaccine elicited an anti-FHbp antibody repertoire directed at FHbp epitopes within the FH binding site, which resulted in greater protective activity than the antibodies elicited by the control vaccine, which targeted FHbp epitopes outside of the FH combining site. Binding of a host protein to a vaccine antigen impairs protective antibody responses, which can be overcome with low-binding mutant antigens. PMID- 27668288 TI - Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate. AB - Vibrio cholerae is the etiological agent of the infectious disease cholera, which is characterized by vomiting and severe watery diarrhea. Recently, V. cholerae clinical isolates have demonstrated increased virulence capabilities, causing more severe symptoms with a much higher rate of disease progression than previously observed. We have identified single nucleotide polymorphisms (SNPs) in four virulence-regulatory genes (hapR, hns, luxO, and vieA) of a hypervirulent V. cholerae clinical isolate, MQ1795. Herein, all SNPs and SNP combinations of interest were introduced into the prototypical El Tor reference strain N16961, and the effects on the production of numerous virulence-related factors, including cholera toxin (CT), the toxin-coregulated pilus (TCP), and ToxT, were analyzed. Our data show that triple-SNP (hapR hns luxO and hns luxO vieA) and quadruple-SNP combinations produced the greatest increases in CT, TCP, and ToxT production. The hns and hns luxO SNP combinations were sufficient for increased TCP and ToxT production. Notably, the hns luxO vieA triple-SNP combination strain produced TCP and ToxT levels similar to those of MQ1795. Certain SNP combinations (hapR and hapR vieA) had the opposite effect on CT, TCP, and ToxT expression. Interestingly, the hns vieA double-SNP combination strain increased TCP production while decreasing CT production. Our findings suggest that SNPs identified in the four regulatory genes, in various combinations, are associated with increased virulence capabilities observed in V. cholerae clinical isolates. These studies provide insight into the evolution of highly virulent strains. IMPORTANCE Cholera, an infectious disease of the small intestine caused by the aquatic bacterium Vibrio cholerae, often results in vomiting and acute watery diarrhea. If left untreated or if the response is too slow, the symptoms can quickly lead to extreme dehydration and ultimately death of the patient. Recent anecdotal evidence of cholera patients suffering from increasingly severe symptoms and of disease progression at a much higher rate than previously observed has emerged. As recent cholera outbreaks caused by increasingly virulent strains have resulted in higher mortality rates, the need to investigate the mechanism(s) allowing this observed increased virulence is apparent. The significance of our research is in identifying the mechanism for increased virulence capabilities, which will allow the development of a model that will greatly enhance our understanding of cholera disease and V. cholerae pathogenesis, leading to broader biomedical impacts, as cholera serves as a model for other enteric diarrheal diseases. PMID- 27668289 TI - Orphanhood by AIDS-Related Causes and Child Mental Health: A Developmental Psychopathology Approach. AB - While the number of new HIV infections has declined, the number of orphans as a result of AIDS-related deaths continues to increase. The aim of this paper was to systematically review empirical research on the mental health of children affected by HIV/AIDS in the developing world, specifically with an eye on developing a theoretical framework to guide intervention and research. Articles for review were gathered by following the Preferred Reporting Items for Systemic Reviews and Meta Analyses (PRISMA standards), reviewed and then organized and synthesized with a Developmental Psychopathology framework. Results showed that the immediate and longterm effects of AIDS orphanhood are moderated by a number of important risk and protective factors that may serve as strategic targets for intervention. Research and clinical implications are discussed. PMID- 27668290 TI - Emerging role of mTOR in the response to cancer therapeutics. AB - The movement toward precision medicine with targeted therapeutics for cancer treatment has been hindered by both innate and acquired resistance. Understanding the molecular wiring and plasticity of oncogenic signaling networks is essential to the development of therapeutic strategies to avoid or overcome resistance. The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) represents a highly integrated signaling node that is dysregulated in the majority of human cancers. Several studies have revealed that sustained mTORC1 inhibition is essential to avoid resistance to targeted therapeutics against the driving oncogenic pathway in a given cancer. Here we discuss the role of mTORC1 in dictating the response of tumors to targeted therapeutics and review recent examples from lung cancer, breast cancer, and melanoma. PMID- 27668292 TI - Enigmatic relationship between chlorophyll a concentrations and photosynthetic rates at Station ALOHA. AB - An ordinary least squares (OLS) analysis of the relationship between chlorophyll a (chl a) concentrations and photosynthetic rates at depths of 5 and 25 m at Station ALOHA produced a slope that was only 28% of the mean productivity index at those depths and an intercept at zero chl a that equaled 70% of the mean photosynthetic rate. OLS regression lines are known to produce a slope and intercept that are biased estimates of the true slope and intercept when the explanatory variable, X, is uncontrolled, but in this case the measurement errors and natural variability of the chl a concentrations were much too small to explain the apparent bias. The bias was traceable to the fact that the photosynthetic rates were determined by more than one explanatory variable, a source of variability that is typically overlooked in discussions of OLS bias. Modeling the photosynthetic rates as a function of the product of chl a and surface irradiance produced a much more accurate and realistic description of the data, but the OLS continued to be biased, presumably because the photosynthetic rates were functions of factors in addition to chl a and surface irradiance (e.g., temperature, macronutrients, trace metals, and vitamins). The results underscore the need to recognize that the absence of bias in an OLS when X is not controlled implies that all scatter in the data about the OLS is due to errors in the dependent variable, an unlikely scenario. In most cases, resolution of the bias problem will require identification of the explanatory variables in addition to X that determine the dependent variable. PMID- 27668291 TI - Activated carbon from flash pyrolysis of eucalyptus residue. AB - Forestry waste (eucalyptus sp) was converted into activated carbon by initial flash pyrolysis followed carbonization and CO2 activation. These residues were obtained from a pilot plant in Spain that produces biofuel, the biochar represented 10-15% in weight. It was observed that the highest activation was achieved at a temperature of 800 degrees C, the specific surface increased with time but, on the contrary, high loss of matter was observed. At 600 degrees C, although there was an important increase of the specific surface and the volume of micropores, at this temperature it was observed that the activation time was not an influential parameter. Finally, at 400 degrees C it was observed that the activation process was not very significant. Assessing the average pore diameter it was found that the lowest value corresponded to the activation temperature of 600 degrees C, which indicated the development of microporosity. When the activation temperature increases up to 800 degrees C the pore diameter increased developing mesoporosity. PMID- 27668293 TI - A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"? AB - With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion. PMID- 27668295 TI - The variable nature of convection in the tropics and subtropics: A legacy of 16 years of the Tropical Rainfall Measuring Mission satellite. AB - For over 16 years, the Precipitation Radar of the Tropical Rainfall Measuring Mission (TRMM) satellite detected the three-dimensional structure of significantly precipitating clouds in the tropics and subtropics. This paper reviews and synthesizes studies using the TRMM radar data to present a global picture of the variation of convection throughout low latitudes. The multiyear data set shows convection varying not only in amount but also in its very nature across the oceans, continents, islands, and mountain ranges of the tropics and subtropics. Shallow isolated raining clouds are overwhelmingly an oceanic phenomenon. Extremely deep and intense convective elements occur almost exclusively over land. Upscale growth of convection into mesoscale systems takes a variety of forms. Oceanic cloud systems generally have less intense embedded convection but can form very wide stratiform regions. Continental mesoscale systems often have more intense embedded convection. Some of the most intense convective cells and mesoscale systems occur near the great mountain ranges of low latitudes. The Maritime Continent and Amazonia exhibit convective clouds with maritime characteristics although they are partially or wholly land. Convective systems containing broad stratiform areas manifest most strongly over oceans. The stratiform precipitation occurs in various forms. Often it occurs as quasi uniform precipitation with strong melting layers connected with intense convection. In monsoons and the Intertropical Convergence Zone, it takes the form of closely packed weak convective elements. Where fronts extend into the subtropics, broad stratiform regions are larger and have lower and sloping melting layers related to the baroclinic origin of the precipitation. PMID- 27668294 TI - INTIMATE PARTNER VIOLENCE IS ASSOCIATED WITH INCREASED CD4+ T-CELL ACTIVATION AMONG HIV-NEGATIVE HIGH-RISK WOMEN. AB - BACKGROUND: Biological pathways mediating the link between intimate partner violence (IPV) and increased HIV risk remain unexplored. We hypothesized that IPV induced stress negatively affects HIV systemic immune defenses and aimed to evaluate whether IPV was associated with immune profiles linked to HIV susceptibility: CD4 activation and diminished regulatory T-cell (Treg) frequency. METHODS: Seventy-five HIV-negative high-risk women were surveyed regarding their IPV experience. They provided blood, urine, and (if present) genital ulcer samples for cortisol, immune assays, and STI testing. Using flow cytometry, we assessed activated CD4+ T-cell (%HLA-DR+/CD38+) and Treg (%CD4+CD25+FoxP3+) frequencies and phenotyping. Nonparametric tests evaluated the association between IPV and immune outcomes. Multivariate regression explored confounding and moderation of the IPV-CD4 activation pathway. RESULTS: Lifetime IPV was associated with increased CD4+ activation (r = 0.331, P = 0.004), a shift in CD4+ phenotype from naive to effector memory (r = 0.343, P = 0.003), and a decrease in naive (%HLA-DR+/CD45RA-) Treg frequency (r = -0.337, P = 0.003). Experiencing IPV over the past year had similar trends. After controlling for sexual IPV, lifetime physical and psychological abuse remained significantly associated with CD4+ activation (P = 0.004 and P = 0.033, respectively). After controlling for race (the only covariate linked to activation), the lifetime IPV-CD4 activation association remained significant (P = 0.012). Alcohol use and depression were identified as potential pathway moderators. CONCLUSION: Our data is the first to suggest an immune link between IPV and HIV, and may help explain differences at the individual level in HIV susceptibility and response to biological HIV prevention strategies. The association of psychological and physical abuse with CD4 activation independent of sexual abuse further supports the existence of a stress-induced immune pathway. PMID- 27668296 TI - Physical Therapy Intervention to Augment Outcomes Of Lymph Node Transfer Surgery for a Breast Cancer Survivor with Secondary Upper Extremity Lymphedema: A Case Report. AB - BACKGROUND AND PURPOSE: Lymphedema is an incurable complication of breast cancer treatment that affects roughly 20 percent of women. It is often managed via complete decongestive therapy, which includes manual lymph drainage, therapeutic compression, skin care, and exercise. Lymph node transfer is a new and expensive surgical intervention that uses one's own lymph nodes and implants them in the affected upper extremity. Previous research has investigated augmenting lymph node transfer surgery with complete decongestive therapy, but there is a lack of evidence regarding the success of focusing lymph drainage against the normal pressure gradient toward a surgical flap located on the wrist. The patient's main motivation for the surgical intervention was to alleviate her daily burden of complete decongestive therapy. The purpose of this case report was to compare the methods and results of pre-surgical complete decongestive physical therapy to a post-operation modified approach that directed lymph fluid away from the major lymphatic ducts and instead toward a surgical flap on the wrist of a patient with lymphedema. CASE DESCRIPTION: A 65-year-old female presented with secondary upper extremity lymphedema following breast cancer treatment. Her circumferential measurements and L-Dex score corroborated this diagnosis, and she had functional deficits in upper extremity range of motion. She was seen for 10 visits of traditional complete decongestive therapy prior to her lymph node transfer surgery and 24 treatments of modified complete decongestive therapy over the course of six months following surgery. OUTCOMES: At six months, the patient had minor improvements in the Functional Assessment of Chronic Illness Therapy Fatigue, Disabilities of the Arm, Shoulder and Hand questionnaire, range of motion, and upper extremity strength. However, her circumferential measurements and L-Dex scores showed a meaningful increase in limb girth. DISCUSSION: The patient's smallest upper extremity volumes were documented before the operation after two weeks of complete decongestive therapy. The surgical intervention supplemented by modified complete decongestive therapy resulted in increased limb girth after six months. Although the patient was able to stop wearing her compression garment while continuing independent manual lymph drainage and upper extremity wrapping, the post-surgical intervention was not a success because the patient's circumferential measurements remained meaningfully higher than at her initial examination. Further research is needed to determine the long-term effects of this surgery when coupled with physical therapy intervention, and whether it has better outcomes than the standard conservative treatment of complete decongestive therapy alone. PMID- 27668297 TI - An Agent-Based Model of School Closing in Under-Vacccinated Communities During Measles Outbreaks. AB - The winter 2014-15 measles outbreak in the US represents a significant crisis in the emergence of a functionally extirpated pathogen. Conclusively linking this outbreak to decreases in the measles/mumps/rubella (MMR) vaccination rate (driven by anti-vaccine sentiment) is critical to motivating MMR vaccination. We used the NOVA modeling platform to build a stochastic, spatially-structured, individual based SEIR model of outbreaks, under the assumption that R0 ~ 7 for measles. We show this implies that herd immunity requires vaccination coverage of greater than approximately 85%. We used a network structured version of our NOVA model that involved two communities, one at the relatively low coverage of 85% coverage and one at the higher coverage of 95%, both of which had 400-student schools embedded, as well as students occasionally visiting superspreading sites (e.g. high-density theme parks, cinemas, etc.). These two vaccination coverage levels are within the range of values occurring across California counties. Transmission rates at schools and superspreading sites were arbitrarily set to respectively 5 and 15 times background community rates. Simulations of our model demonstrate that a 'send unvaccinated students home' policy in low coverage counties is extremely effective at shutting down outbreaks of measles. PMID- 27668298 TI - Modeling Social Capital as Dynamic Networks to Promote Access to Oral Healthcare. AB - Social capital, as comprised of human connections in social networks and their associated benefits, is closely related to the health of individuals, communities, and societies at large. For disadvantaged population groups such as older adults and racial/ethnic minorities, social capital may play a particularly critical role in mitigating the negative effects and reinforcing the positive effects on health. In this project, we model social capital as both cause and effect by simulating dynamic networks. Informed in part by a community-based health promotion program, an agent-based model is contextualized in a GIS environment to explore the complexity of social disparities in oral and general health as experienced at the individual, interpersonal, and community scales. This study provides the foundation for future work investigating how health and healthcare accessibility may be influenced by social networks. PMID- 27668299 TI - Strong [(68)Ga]PSMA-HBED-CC accumulation in non-cancerous prostate tissue surrounding a PSMA-negative prostate carcinoma recurrence. PMID- 27668300 TI - Primary lymphoma involving cranial nerves and cauda equina detected by (18)F-FDG PET/CT and MRI. PMID- 27668302 TI - Devitalized bone in a multi-fragment femoral shaft fracture detected by (18)F-NaF PET-CT. PMID- 27668301 TI - The role of (18)F-FDG PET/CT in diagnosis and therapeutic approach in small child with MSMD. PMID- 27668304 TI - Regiodiscriminating Reactivity of Isolable NHC-Coordinated Disilenyl Germylene and Its Cyclic Isomer. AB - An isolable NHC-coordinated disilenyl germylene R2Si?SiR-GePh.NHCiPr2Me2 (5b: R = 2,4,6-triisopropylphenyl, NHCiPr2Me2 = 1,3-diisopropyl-4,5-dimethylimidazol-2 ylidene) is obtained from the reaction of the alpha-chloro silyl functionalized heavier vinylidene analogue R2(Cl)Si-RSi?Ge.NHCiPr2Me2 with phenyllithium. The disilenyl germylene 5b isomerizes at 40 degrees C to the NHC-adduct of the corresponding heavier cyclopropylidene analogue 6b. Both 5b and 6b display near perfect regiodiscrimination in their reactions with phenylacetylene and xylyl isocyanide, affording in the case of each reagent two different regioisomers of NHC-coordinated cyclic germylenes. DFT calculations reveal that the Si?Si bond accounts for the high reactivity of 5b even at low temperature while in the case of cyclic 6b the low-valent germanium center requires a considerable thermal activation. PMID- 27668303 TI - Trefoil factor family 2 expression inhibits gastric cancer cell growth and invasion in vitro via interactions with the transcription factor Sp3. AB - The trefoil factor family (TFF) is a group of short secretory peptides of gastric mucous neck cells. The loss of TFF2 protein expression enhances gastric inflammation and occurs in gastric cancer. In this study, we examined the effect of TFF2 on gastric cancer cell lines in vitro and characterized the interaction between TFF2 and Sp3, including the mechanisms that mediate this interaction, using genomics and proteomics approaches, as well as genetics techniques, such as RNA interference and gene knockdown. Assays were performed to examine the role of TFF2 and Sp3 in cancer cell proliferation, invasion and migration. We found that TFF2 expression inhibited the proliferation and invasion capacity of gastric cancer cells, and induced apoptosis. TFF2 interacted with the Sp3 protein, as shown by immunofluorescence staining and immunoprecipitation with western blot analysis. Sp3 knockdown in gastric cancer cells antagonized TFF2 antitumor activity. Additionally, TFF2 upregulated the expression of pro-apoptotic proteins, such as Bid, but downregulated the expression of NF-kappaB and the anti apoptotic proteins, Bcl-xL and Mcl-1. By contrast, Sp3 knockdown significantly blocked TFF2 activity, affecting the expression of these proteins. The data from our study demonstrate that the antitumor activity of TFF2 is mediated by an interaction with the Sp3 protein in gastric cancer cells. Additional in vivo and ex vivo warrned in order to fully characterize this interaction. PMID- 27668305 TI - Fabrication of Propeller-Shaped Supra-amphiphile for Construction of Enzyme Responsive Fluorescent Vesicles. AB - Propeller-shaped molecules have been recognized to display fantastic AIE (aggregation induced emission), but they can hardly self-assemble into nanostructures. Herein, we for the first time report that ionic complexation between a water-soluble tetrapheneyl derivative and an enzyme substrate in aqueous media produces a propeller-shaped supra-amphiphile that self-assembles into enzyme responsive fluorescent vesicles. The supra-amphiphile was fabricated upon complexation between a water-soluble propeller-shaped AIE luminogen TPE-BPA and myristoylcholine chloride (MChCl) in aqueous media. MChCl filled in the intramolecular voids of propeller-shaped TPE-BPA upon supra-amphiphile formation, which endows the supra-amphiphile superior self-assembling ability to the component molecules thus leading to the formation of fluorescent vesicles. Because MChCl is the substrate of cholinesterases, the vesicles dissemble in the presence of cholinesterases, and the fluorescent intensity can be correlated to the level of enzymes. The resulting fluorescent vesicles may be used to recognize the site of Alzheimer's disease, to encapsulate the enzyme inhibitor, and to release the inhibitor at the disease site. PMID- 27668306 TI - Photocontrollable Intermittent Release of Doxorubicin Hydrochloride from Liposomes Embedded by Azobenzene-Contained Glycolipid. AB - Azobenzene-contained glycolipids GlyAzoCns, newly structured azobenzene derivatives, which have an azobenzene moiety between the galactosyl and carbon chains of various sizes, have been synthesized. The GlyAzoCns undergo reversible photoinduced isomerization in both ethanol solution (free state) and liposomal bilayer (restricted state) upon irradiation with UV and vis light alternately. The drug release of Liposome@Gly induced by isomerization was found to be an instantaneous behavior. The photoinduced control of DOX release from liposome was investigated in various modes. The Liposome@Glys have been found to keep the entrapped DOX stably in the dark with less than 10% leakage in 10 h but release nearly 100% of cargos instantaneously with UV irradiation. The molecular structure of GlyAzoCns and the property of the liposomal bilayer were considered as important factors influencing drug release. Among the synthesized GlyAzoCns, GlyAzoC7 was shown to be the most efficient photosensitive actuator for controlling drug release. A lower proportion of cholesterol in Liposome@Glys was conducive to promote the release amount. Results indicated that the synthesized GlyAzoCns could act as a role of smart actuators in the liposome bilayer and control the drug to release temporarily and quantitatively. PMID- 27668307 TI - Lattice Dynamics of the Rhombohedral Polymorphs of CaSi2. AB - The structures of two trigonal-rhombohedral CaSi2 polymorphs (space group R3m) were studied by X-ray diffraction and polarized Raman scattering spectroscopy. Raman-active even-parity vibrational modes of A1g and Eg are unambiguously identified and assigned to the specific lattice eigenmodes. Experimental data are found to be in very good agreement with those predicted by density functional theory lattice dynamics calculations. The transformation of 6R structural modification of CaSi2 into its 3R polymorph, by high-temperature annealing in vacuum is also reported. PMID- 27668308 TI - You think you know where you looked? You better look again. AB - People are surprisingly bad at knowing where they have looked in a scene. We tested participants' ability to recall their own eye movements in 2 experiments using natural or artificial scenes. In each experiment, participants performed a change-detection (Exp.1) or search (Exp.2) task. On 25% of trials, after 3 seconds of viewing the scene, participants were asked to indicate where they thought they had just fixated. They responded by making mouse clicks on 12 locations in the unchanged scene. After 135 trials, observers saw 10 new scenes and were asked to put 12 clicks where they thought someone else would have looked. Although observers located their own fixations more successfully than a random model, their performance was no better than when they were guessing someone else's fixations. Performance with artificial scenes was worse, though judging one's own fixations was slightly superior. Even after repeating the fixation-location task on 30 scenes immediately after scene viewing, performance was far from the prediction of an ideal observer. Memory for our own fixation locations appears to add next to nothing beyond what common sense tells us about the likely fixations of others. These results have important implications for socially important visual search tasks. For example, a radiologist might think he has looked at "everything" in an image, but eye tracking data suggest that this is not so. Such shortcomings might be avoided by providing observers with better insights of where they have looked. (PsycINFO Database Record PMID- 27668309 TI - Exploring Protein Stability by Comparative Molecular Dynamics Simulations of Homologous Hyperthermophilic, Mesophilic, and Psychrophilic Proteins. AB - In the present studies, we analyzed the influence of temperature on the stability and dynamics of the alpha subunit of tryptophan synthase (TRPS) from hyperthermophilic, mesophilic, and psychrophilic homologues at different temperatures by molecular dynamics simulations. Employing different indicators such as root-mean-square deviations, root-mean-square fluctuations, principal component analysis, and free energy landscapes, this study manifests the diverse behavior of these homologues with changes in temperature. Especially, an enhancement in the collective motions, classified as representative motions, is observed at high temperature. Similarly, the criterion for the selection of electrostatic interactions in terms of their life span (duty cycle) has indeed helped in identifying the short- and long-lived electrostatic interactions and how they affect the protein's overall stability at different temperatures. Rigidity and flexibility patterns of the homologous proteins are examined using FIRST software along with the calculation of duty cycles with various threshold limits at different temperatures. Rigid cluster decomposition in TRPS of psychrophilic, mesophilic, and hyperthermophilic origin identifies the flexible and rigid regions in the protein. Early loss of rigidity is observed in mesophilic TRPS via loss of contact between the major fragments of the protein compared with the other homologues. In spite of the high similarity of their three-dimensional structures, the overall responses of the three proteins to varying temperatures are significantly different. PMID- 27668310 TI - Improved Efficiency and Enhanced Color Quality of Light-Emitting Diodes with Quantum Dot and Organic Hybrid Tandem Structure. AB - Light-emitting diodes based on organic (OLEDs) and colloidal quantum dot (QLEDs) are widely considered as next-generation display technologies because of their attractive advantages such as self-emitting and flexible form factor. The OLEDs exhibit relatively high efficiency, but their color saturation is quite poor compared with that of QLEDs. In contrast, the QLEDs show very pure color emission, but their efficiency is lower than that of OLEDs currently. To combine the advantages and compensate for the weaknesses of each other, we propose a hybrid tandem structure which integrates both OLED and QLED in a single device architecture. With ZnMgO/Al/HATCN interconnecting layer, hybrid tandem LEDs are successfully fabricated. The demonstrated hybrid tandem devices feature high efficiency and high color saturation simultaneously; for example, the devices exhibit maximum current efficiency and external quantum efficiency of 96.28 cd/A and 25.90%, respectively. Meanwhile, the full width at half-maximum of the emission spectra is remarkably reduced from 68 to 44 nm. With the proposed hybrid tandem structure, the color gamut of the displays can be effectively increased from 81% to 100% NTSC. The results indicate that the advantages of different LED technologies can be combined in a hybrid tandem structure. PMID- 27668311 TI - Low-Temperature Catalytic Decomposition of 130 Tetra- to Octa-PCDD/Fs Congeners over CuOX and MnOX Modified V2O5/TiO2-CNTs with the Assistance of O3. AB - In this study, a reliable and steady PCDD/F generation system was utilized to investigate the performance of catalysts, in which 130 congeners of tetra- to octapolychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) vapors were studied under simulated flue gas with/without O3. TiO2 and carbon nanotubes (CNTs) supported vanadium oxides (VOX/TiO2-CNTs) modified with MnOX and CuOX, which were reported to be beneficial to the decomposition of model molecules, were found to have a negative effect on the removal of real PCDD/Fs in the simulated flue gas without O3. Moreover, the addition of MnOX presented different effects depending on whether CuOX existed in catalysts or not, which was also contrary to its effects on the degradation of model molecules. In an O3 containing atmosphere, low chlorination level PCDD/Fs congeners were removed well over VOX-MnOX/TiO2-CNTs, while high chlorination level PCDD/Fs congeners were removed well over VOX-CuOX/TiO2-CNTs. Fortunately, all PCDD/Fs congeners decomposed well over VOX-MnOX-CuOX/TiO2-CNTs. Finally, the effects of tetra- to octachlorination level for the adsorption and degradation behaviors of PCDD/Fs congeners were also investigated. PMID- 27668313 TI - Laplace Pressure of Individual H2 Nanobubbles from Pressure-Addition Electrochemistry. AB - The Young-Laplace equation is central to the thermodynamic description of liquids with highly curved interfaces, e.g., nanoscale droplets and their inverse, nanoscale bubbles. The equation relates the pressure difference across an interface to its surface tension and radius of curvature, but the validity in using the macroscopic surface tension for describing curved interfaces with radii smaller than tens of nanometers has been questioned. Here we present electrochemical measurement of Laplace pressures within single H2 bubbles between 7 and 200 nm radius (corresponding, respectively, to between 200 and 7 atm). Our results demonstrate a linear relationship between a bubble's Laplace pressure and its reciprocal radius, verifying the classical thermodynamic description of H2 nanobubbles as small as ~10 nm. PMID- 27668314 TI - Nanoelectronic Heterodyne Sensor: A New Electronic Sensing Paradigm. AB - Nanoelectronic devices based on nanomaterials such as nanowires, carbon nanotubes, graphene, and other 2D nanomaterials offer extremely large surface-to volume ratios, high carrier mobility, low power consumption, and high compatibility for integration with modern electronic technologies. These distinct advantages promise great potential for nanoelectronic devices as next generation chemical and biological sensors. Currently, majority of existing nanoelectronic sensors are direct current (DC) sensors, which rely ubiquitously on detection of conductance change associated with molecular adsorption. However, despite the simplicity of the conventional DC sensing technology, it also has severe limitations such as the Debye screening effect in ionic solutions, and the speed sensitivity trade-off for the detection of charge-neutral molecules. Hence, the development of nanoelectronic sensors calls for new sensing platform technologies that can truly showcase the advantages of electronic sensors. In this Account, we will summarize recent efforts from our group on the development of a new electronic sensing paradigm, the nanoelectronic heterodyne sensors. Unlike conventional charge-detection based sensors, the heterodyne sensor explores the frequency mixing response between molecular dipoles and a nanoscale transistor. As an example, we first discuss the capability of heterodyne sensing in gas sensing applications by using graphene devices. Rapid (down to 0.1 s) and sensitive (down to 1 ppb) detection of a wide range of vapor analytes is achieved, representing orders of magnitude improvement over state-of-the-art nanoelectronic sensors. Furthermore, the heterodyne sensing technique enables electrical probing and tuning of the noncovalent physisorption of polar molecules on graphene surface for the first time. These results provide insight into small molecule-nanomaterial interaction dynamics and signify the ability to electrically tailor interactions, which can lead to rational designs of complex chemical processes for catalysis and drug discovery. Finally, we discuss the application of heterodyne sensing in solution for chemical and biological sensors by using carbon nanotube devices. The fundamental ionic screening effect can be mitigated by operating carbon nanotube field effect transistor as a heterodyne biosensor. Electrical detection of streptavidin binding to biotin in 100 mM buffer solution can be achieved at a frequency beyond 1 MHz. The results should promise a new biosensing platform for point-of-care detection, where biosensors functioning directly in physiologically relevant condition are desired. PMID- 27668315 TI - Evaluation of Lecithinized Superoxide Dismutase for the Prevention of Acute Respiratory Distress Syndrome in Animal Models. AB - For acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) is a life-saving intervention without alternative; however, MV can cause ventilator induced lung injury. Reactive oxygen species (ROS) play important roles in the pathogenesis of both ARDS and ventilator-induced lung injury. Lecithinized superoxide dismutase (PC-SOD) overcomes the limitations of superoxide dismutase such as low tissue affinity and low stability in plasma. In this study, we examined the effect of PC-SOD on tissue injury, edema, and inflammation in the lung and other organs of mice subjected to cecal ligation and puncture (CLP), LPS administration, or MV. The severity of the lung injury was assessed on the basis of vascular permeability, histopathologic evaluation, and lung mechanics. Intravenous PC-SOD administration (the first administered just before CLP) increased the survival rate and decreased vascular permeability in mice subjected to CLP. PC-SOD, but not dexamethasone or sivelestat sodium hydrate (sivelestat), suppressed CLP-induced kidney injury and systemic inflammation. PC-SOD also suppressed vascular permeability, tissue injury, and inflammation in the lung induced by LPS administration. Moreover, PC-SOD, but not dexamethasone or sivelestat, suppressed vascular permeability, edema, tissue injury, and mechanical alterations in the lung induced by MV. In vivo imaging analysis of ROS revealed that CLP, LPS administration, and MV increased the level of ROS and that this increase was suppressed by PC-SOD. The results of this study thus suggest that, on the basis of its ROS-reducing properties, intravenous administration of PC-SOD may be beneficial for patients at high risk of developing ARDS. PMID- 27668316 TI - Expanding the nematode model system: The molecular basis of inflammation and infection recovery in C. elegans. PMID- 27668317 TI - Effects of PARP-1 inhibitor and ERK inhibitor on epithelial mesenchymal transitions of the ovarian cancer SKOV3 cells. AB - BACKGROUND: To assess the effects of the poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 and ERK1/2 inhibitor U0126 on the proliferation and epithelial mesenchymal transitions (EMT) of cisplatin resistant ovarian cancer SKOV-3 cells. METHODS: Proliferation of SKOV-3 cells was evaluated using a 3-(4,5 dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide assay with PJ34 and U0126 treatment. Expression changes of E-cadherin and vimentin with PJ34 and U0126 treatment was examined using Western blot and quantitative PCR. In addition, invasion assay was performed in cells treated with PJ34 and U0126. RESULTS: PJ34 and U0126 inhibited proliferation of SKOV-3 cells in a time dependent manner. PJ34 and U0126 suppressed the expression of vimentin and enhanced the expression of E-cadherin. PJ34 and U0126 reduced cell invasion. The inhibitory effects of PJ34 and U0126 were stronger than PJ34 alone. PJ34 inhibited the proliferation and invasion of SKOV-3 cells which can be enhanced by ERK1/2 inhibitor U0126. CONCLUSIONS: These inhibitory effects are partially due to PARP-1 and ERK1/2 mediated attenuation of EMT activity. PMID- 27668318 TI - Health Literacy and Online Health Information Processing: Unraveling the Underlying Mechanisms. AB - The usefulness of the Internet as a health information source largely depends on the receiver's health literacy. This study investigates the mechanisms through which health literacy affects information recall and website attitudes. Using 2 independent surveys addressing different Dutch health websites (N = 423 and N = 395), we tested the mediating role of cognitive load, imagination ease, and website involvement. The results showed that the influence of health literacy on information recall and website attitudes was mediated by cognitive load and imagination ease but only marginally by website involvement. Thus, to improve recall and attitudes among people with lower health literacy, online health communication should consist of information that is not cognitively demanding and that is easy to imagine. PMID- 27668321 TI - Catalytic Asymmetric Synthesis of Morpholines. Using Mechanistic Insights To Realize the Enantioselective Synthesis of Piperazines. AB - An efficient and practical catalytic approach for the enantioselective synthesis of 3-substituted morpholines through a tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions is described. Starting from ether-containing aminoalkyne substrates, a commercially available bis(amidate)bis(amido)Ti catalyst is utilized to yield a cyclic imine that is subsequently reduced using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts DPEN] (eta6-p-cymene), to afford chiral 3-substituted morpholines in good yield and enantiomeric excesses of >95%. A wide range of functional groups is tolerated. Substrate scope investigations suggest that hydrogen-bonding interactions between the oxygen in the backbone of the ether-containing substrate and the [(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee's. This insight led to a mechanistic proposal that predicts the observed absolute stereochemistry. Most importantly, this mechanistic insight allowed for the extension of this strategy to include N as an alternative hydrogen bond acceptor that could be incorporated into the substrate. Thus, the catalytic, enantioselective synthesis of 3-substituted piperazines is also demonstrated. PMID- 27668319 TI - MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition. AB - It is observed that upregulation of DNMT3B enzyme in some cancers, including colon cancer, could lead to silencing of tumor suppressor genes. MiR-339 and miR 766 have been predicted to target 3'UTR of DNMT3B gene. Luciferase reporter assay validated that individual and co-transfection of miR-766 and miR-339 into the HEK293T cell reduced luciferase activity to 26% +/- 0.41%, 43% +/- 0.42 and 64% +/- 0.52%, respectively, compared to the control (P < 0.05). Furthermore, transduction of miR-339 and miR-766 expressing viruses into colon cancer cell lines (SW480 and HCT116) decreased DNMT3B expression (1.5, 3-fold) and (3, 4 fold), respectively. In addition, DNA methylation of some tumor suppressor genes decreased. Expression of these genes such as SFRP1 (2 and 1.6-fold), SFRP2 (0.07 and 4-fold), WIF1 (0.05 and 4-fold), and DKK2 (2 and 4-fold) increased in SW-339 and SW-766 cell lines; besides, expression increments for these genes in HCT-339 and HCT-766 cell lines were (2.8, 4-fold), (0.005, 1.5-fold), (1.7 and 3-fold) and (0.04, 1.7-fold), respectively. Also, while in SW-766, cell proliferation reduced to 2.8% and 21.7% after 24 and 48 hours, respectively, SW-339 showed no reduced proliferation. Meanwhile, HCT-766 and HCT-339 showed (3.5%, 12.8%) and (18.8%, 33.9%) reduced proliferation after 24 and 48 hours, respectively. Finally, targeting DNMT3B by these miRs, decreased methylation of tumor suppressor genes such as SFRP1, SFRP2, WIF1 and DKK2 in the mentioned cell lines, and returned the expression of these tumor suppressor genes which can contribute to lethal effect on colon cancer cells and reducing tumorigenicity of these cells. PMID- 27668320 TI - Patterns of youth tobacco and polytobacco usage: The shift to alternative tobacco products. AB - BACKGROUND: Despite significant declines in youth cigarette smoking, overall tobacco usage remains over 20% as non-cigarette tobacco product usage is increasingly common and polytobacco use (using 1+ tobacco product) remains steady. OBJECTIVES: The present study was designed to identify patterns of youth tobacco use and examine associations with sociodemographic characteristics and tobacco dependence. METHODS: The current analysis uses Latent Class Analysis (LCA) to examine the 6,958 tobacco users (n = 2,738 female) in the National Youth Tobacco Survey (2012 and 2013). We used as indicators past month use of tobacco products (cigarettes, cigars, smokeless tobacco, e-cigarettes, hookah, snus, pipes, bidis, and kreteks) and regressed resulting classes on sociodemographic characteristics and tobacco dependence. RESULTS: Nine classes emerged: cigarette smokers (33.4% of sample, also included small probabilities for use of cigars and e-cigarettes), cigar smokers (16.8%, nearly exclusive), smokeless tobacco users (12.3%, also included small probabilities for cigarettes, cigars, snus), hookah smokers (11.8%), tobacco smokers/chewers (10.7%, variety of primarily traditional tobacco products), tobacco/hookah smokers (7.2%), tobacco/snus/e-cig users (3.3%), e-cigarette users (2.9%,), and polytobacco users (1.7%, high probabilities for all products). Compared to cigarette smokers, tobacco/hookah smokers and hookah smokers were more likely to report Hispanic ethnicity. Polytobacco users were more likely to report dependence (AOR:2.77, 95% CI:[1.49 5.18]), whereas e-cigarette users were less likely (AOR:0.49, 95% CI:[0.24 0.97]). CONCLUSION: Findings are consistent with other research demonstrating shifts in adolescent tobacco product usage towards non-cigarette tobacco products. Continuous monitoring of these patterns is needed to help predict if this shift will ultimately result in improved public health. PMID- 27668322 TI - The variability of standard artificial soils: cadmium and phenanthrene sorption measured by a batch equilibrium method. AB - Artificial soil (AS) is used in soil ecotoxicology as a test medium or reference matrix. AS is prepared according to standard OECD/ISO protocols and components of local sources are usually used by laboratories. This may result in significant inter-laboratory variations in AS properties and, consequently, in the fate and bioavailability of tested chemicals. In order to reveal the extent and sources of variations, the batch equilibrium method was applied to measure the sorption of 2 model compounds (phenanthrene and cadmium) to 21 artificial soils from different laboratories. The distribution coefficients (Kd) of phenanthrene and cadmium varied over one order of magnitude: from 5.3 to 61.5L/kg for phenanthrene and from 17.9 to 190L/kg for cadmium. Variations in phenanthrene sorption could not be reliably explained by measured soil properties; not even by the total organic carbon (TOC) content which was expected. Cadmium logKd values significantly correlated with cation exchange capacity (CEC), pHH2O and pHKCl, with Pearson correlation coefficients of 0.62, 0.80, and 0.79, respectively. CEC and pHH2O together were able to explain 72% of cadmium logKd variability in the following model: logKd=0.29pHH2O+0.0032 CEC -0.53. Similarly, 66% of cadmium logKd variability could be explained by CEC and pHKCl in the model: logKd=0.27pHKCl+0.0028 CEC -0.23. Variable cadmium sorption in differing ASs could be partially treated with these models. However, considering the unpredictable variability of phenanthrene sorption, a more reliable solution for reducing the variability of ASs from different laboratories would be better harmonization of AS preparation and composition. PMID- 27668324 TI - Physician and government disconnect is becoming a chasm. PMID- 27668323 TI - Association of paraoxonase 1 (PON1) gene polymorphisms and concentration with essential hypertension. AB - Human serum paraoxonase 1 (PON1) is carried by high-density lipoprotein in blood circulation and is shown to be effective in preventing oxidized phospholipids carried by low-density lipoprotein particles, thus it acts as an antioxidant. Polymorphism in this gene has been investigated for many metabolic diseases, but it is not thought to be a genetic risk factor for essential hypertension. The aim of this study was to determine whether there was an association between PON1 gene polymorphisms and concentration with essential hypertension. The study population was comprised of 100 patients with essential hypertension and 100 healthy controls. One promoter region [C(-108)T] and two coding region (Q192R and L55M) polymorphisms in the PON1 gene were genotyped in individuals by using the TaqMan assay. Plasma PON1 concentration in all volunteers was also measured spectrophotometrically by the enzyme-linked immunosorbent assay method. The genotype and allele frequencies of the PON1 C(-108)T polymorphism showed significant differences between the essential hypertensive and control groups (CT vs. CC: p<0.001; T allele vs. C allele: p<0.001). There was no significant difference for the PON1 L55M polymorphism between the groups, while the heterozygote genotype of the PON1 Q192R polymorphism showed significant difference (p = 0.03). The PON1 concentration was also found to be significantly lower in hypertensive patients (p < 0.001). Decline in the level of PON1 gene may be one of the main factors in the development of essential hypertension, and the PON1 C(-108)T polymorphism may have a prognostic value in the patients with essential hypertension. PMID- 27668325 TI - [Profession medicale et gouvernement : l'abime se creuse]. PMID- 27668326 TI - A review of the literature and discussion: establishing a consensus for the definition of post-mastectomy pain syndrome to provide a standardized clinical and research approach. AB - SUMMARY: Chronic pain presents a management challenge for physicians and patients alike, and post-mastectomy pain is no exception. In this issue, Waltho and Rockwell present a review of post-mastectomy pain syndrome (PMPS) and propose a standard definition that should allow future studies to be comparable. The proposed definition of "post-breast surgery pain syndrome" includes pain after any type of breast surgery that is of at least moderate intensity and comprises neuropathic qualities, that is present in the ipsilateral breast/chest/arm, that lasts longer than 6 months and is present at least half the time. Further work is needed to clarify whether this pain syndrome is in fact driven by neuralgia resulting from the axillary dissection component of breast cancer surgery. PMID- 27668327 TI - Correction: The optimal time for surgery in women with serous ovarian cancer. PMID- 27668328 TI - Five things they don't teach you in medical school. AB - SUMMARY: You graduate from medical school with dreams of beginning your residency, during which you will study and train within the specialty you love more than any other. While you may be book-smart at this point in your career, medical school does not teach you everything you need to know. During residency you will learn the didactic and technical requirements for your future staff job, but medical school won't explicitly address many of the crucial "dos and don'ts" of a successful 2- to 5-year postgraduate training voyage. Here we discuss a few of the important things about residency that you'll need to know that they don't teach you in medical school. PMID- 27668329 TI - Conservative versus operative management in stable patients with penetrating abdominal trauma: the experience of a Canadian level 1 trauma centre. AB - BACKGROUND: The goal of conservative management (CM) of penetrating abdominal trauma is to avoid nontherapeutic laparotomies while identifying injuries early. Factors that may predict CM failure are not well established, and the experience of CM has not been well described in the Canadian context. METHODS: We searched a Canadian level 1 trauma centre database for all penetrating abdominal traumas treated between 2004 and 2014. Hemodynamically stable patients without peritonitis and without clear indications for immediate surgery were considered potential candidates for CM, and were included in the study. We compared those who were managed with CM with those who underwent immediate operative management (OM). Outcomes included mortality and length of stay (LOS). Further analysis was performed to identify predictors of CM failure. RESULTS: A total of 72 patients with penetrating abdominal trauma were classified as potential candidates for CM. Ten patients were managed with OM, and 62 with CM, with 9 (14.5%) ultimately failing CM and requiring laparotomy. The OM and CM groups were similar in terms of age, sex, injury severity, mechanism and number of injuries. There were no deaths in either group. The LOS in the intensive care (ICU)/trauma unit was 4.8 +/- 3.2 days in the OM group and 2.9 +/- 2.6 days in the CM group (p = 0.039). The only predictor for CM failure was intra-abdominal fluid on computed tomography (CT) scan (odds ratio 5.3, 95% confidence interval 1.01-28.19). CONCLUSION: In select patients with penetrating abdominal trauma, CM is safe and results in a reduced LOS in the ICU/trauma unit of 1.9 days. Fluid on CT scan is a predictor for failure. PMID- 27668330 TI - The impact of blood transfusion on perioperative outcomes following gastric cancer resection: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database. AB - BACKGROUND: Red blood cell transfusions (RBCT) carry risk of transfusion-related immunodulation that may impact postoperative recovery. This study examined the association between perioperative RBCT and short-term postoperative outcomes following gastrectomy for gastric cancer. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we compared outcomes of patients (transfused v. nontransfused) undergoing elective gastrectomy for gastric cancer (2007-2012). Outcomes were 30-day major morbidity, mortality and length of stay. The association between perioperative RBCT and outcomes was estimated using modified Poisson, logistic, or negative binomial regression. RESULTS: Of the 3243 patients in the entire cohort, we included 2884 patients with nonmissing data, of whom 535 (18.6%) received RBCT. Overall 30-day major morbidity and mortality were 20% and 3.5%, respectively. After adjustment for baseline and clinical characteristics, RBCT was independently associated with increased 30-day mortality (relative risk [RR] 3.1, 95% confidence interval [CI] 1.9-5.0), major morbidity (RR 1.4, 95% CI 1.2-1.8), length of stay (RR 1.2, 95% CI 1.1-1.2), infections (RR 1.4, 95% CI 1.1-1.6), cardiac complications (RR 1.8, 95% CI 1.0-3.2) and respiratory failure (RR 2.3, 95% CI 1.6-3.3). CONCLUSION: Red blood cell transfusions are associated with worse postoperative short-term outcomes in patients with gastric cancer. Blood management strategies are needed to reduce the use of RBCT after gastrectomy for gastric cancer. PMID- 27668331 TI - Efficacy of intraoperative cell salvage in decreasing perioperative blood transfusion rates in first-time cardiac surgery patients: a retrospective study. AB - BACKGROUND: Evidence regarding the safety and efficacy of intraoperative cell salvage (ICS) in transfusion reduction during cardiac surgery remains conflicting. We sought to evaluate the impact of routine ICS on outcomes following cardiac surgery. METHODS: We conducted a retrospective analysis of patients who underwent nonemergent, first-time cardiac surgery 18 months before and 18 months after the implementation of routine ICS. Perioperative transfusion rates, postoperative bleeding, clinical and hematological outcomes, and overall cost were examined. We used multivariable logistic regression modelling to determine the risk-adjusted effect of ICS on likelihood of perioperative transfusion. RESULTS: A total of 389 patients formed the final study population (186 undergoing ICS and 203 controls). Patients undergoing ICS had significantly lower perioperative transfusion rates of packed red blood cells (pRBCs; 33.9% v. 45.3% p = 0.021), coagulation products (16.7% v. 32.5% p < 0.001) and any blood product (38.2% v. 52.7%, p = 0.004). Patients receiving ICS had decreased mediastinal drainage at 12 h (mean 320 [range 230-550] mL v. mean 400 [range 260 690] mL, p = 0.011) and increased postoperative hemoglobin (mean 104.7 +/- 13.2 g/L v. 95.0 +/- 11.9 g/L, p < 0.001). Following adjustment for other baseline and intraoperative covariates, ICS emerged as an independent predictor of lower perioperative transfusion rates of pRBCs (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31-0.87), coagulation products (OR 0.41, 95% CI 0.24-0.71) and any blood product (OR 0.47, 95% CI 0.29-0.77). Additionally, ICS was associated with a cost benefit of $116 per patient. CONCLUSION: Intraoperative cell salvage could represent a clinically cost-effective way of reducing transfusion rates in patients undergoing cardiac surgery. Further research on systematic ICS is required before recommending it for routine use. PMID- 27668332 TI - Length of stay, wait time to surgery and 30-day mortality for patients with hip fractures after the opening of a dedicated orthopedic weekend trauma room. AB - BACKGROUND: In September 2011, Kingston General Hospital (KGH) opened a dedicated orthopedic weekend trauma room. Previously, 1 weekend operating room (OR) was used by all surgical services. We assessed the impact this dedicated weekend trauma room had on hospital length of stay (LOS), time to surgery and 30-day mortality for patients with hip fractures. METHODS: Patients admitted between Oct. 1, 2009, and Sept. 30, 2012, were identified through our trauma registry, representing the 2 years before and 1 year after the opening of the orthopedic weekend trauma room. We documented type of fracture, mode of fixation, age, sex, American Society of Anesthesiologists (ASA) score, time to OR, LOS, discharge disposition and 30-day mortality. We excluded patients with multiple fractures, open fractures and those requiring trauma team activation. RESULTS: Our study included 609 patients (405 pre- and 204 post-trauma room opening). Mean LOS decreased from 11.6 to 9.4 days (p = 0.005) and there was a decreasing trend in mean time to OR from 31.5 to 28.5 hours (p = 0.16). There was no difference in 30 day mortality (p = 0.24). The LOS decreased by an average of 2 days following opening of the weekend trauma room (p = 0.031) and by an average of 2.2 additional days if the patient was admitted on the weekend versus during the week (p = 0.024). CONCLUSION: The weekend trauma OR at KGH significantly decreased the LOS and appears to have decreased wait times to surgery. Further analysis is needed to assess the cost-effectiveness of the current strategy, the long-term outcome of this patient population and the impact the additional orthopedic weekend trauma room has had on other surgical services (i.e., general surgery) and their patients. PMID- 27668333 TI - Post-breast surgery pain syndrome: establishing a consensus for the definition of post-mastectomy pain syndrome to provide a standardized clinical and research approach - a review of the literature and discussion. AB - BACKGROUND: Post-mastectomy pain syndrome (PMPS) is a frequent complication of breast surgery. There is currently no standard definition for this chronic pain syndrome. The purpose of this review was to establish a consensus for defining PMPS by identifying the various elements included in the definitions and how they vary across the literature, determining how these definitions affect the methodological components therein, and proposing a definition that appropriately encompasses all of the appropriate elements. METHODS: We searched PubMed to retrieve all studies and case reports on PMPS, and we analyzed definitions of PMPS, inclusion/exclusion criteria, and methods of measuring PMPS. RESULTS: Twenty-three studies were included in this review. We identified 7 independent domains for defining PMPS: surgical breast procedure, neuropathic nature, pain of at least moderate intensity, protracted duration, frequent symptoms, appropriate location of the symptoms and exacerbation with movement. These domains were used with varying frequency. Inclusion/exclusion criteria and methods for assessing PMPS also varied markedly. CONCLUSION: To prevent future discrepancies in both the clinical and research settings, we propose a new and complete definition based on the results of our review: PMPS is pain that occurs after any breast surgery; is of at least moderate severity; possesses neuropathic qualities; is located in the ipsilateral breast/chest wall, axilla, and/or arm; lasts at least 6 months; occurs at least 50% of the time; and may be exacerbated by movements of the shoulder girdle. PMID- 27668334 TI - Users' guide to the surgical literature: how to assess an article about harm in surgery. AB - CLINICALSCENARIO: You are a new plastic surgeon in the community and you are referred a patient interested in breast reconstruction. The patient is a 35-year old female school teacher who had a bilateral prophylactic mastectomy 2 years earlier, as she was a BRCA gene carrier. Since she is of a petite build with very little subcutaneous tissue or extra skin in the lower abdomen, you decide that she is not a suitable candidate for an abdomen-based autologous tissue reconstruction. You recommend the technique of tissue expansion and silicone gel implants. She is concerned, however, about the possibility of anaplastic large cell lymphoma (ALCL) developing in her breasts. She read in a magazine recently that ALCL, an unusual form of breast cancer, has been occurring in patients who have breast implants. She is very concerned that she might be at risk and asks for your opinion as to whether she should proceed with the procedure or not. PMID- 27668335 TI - Upper limb ischemia: an uncommon clinical situation? PMID- 27668336 TI - Arterial thoracic outlet syndrome: rare and triggering. AB - Arterial thoracic outlet syndrome (TOS) is the least common type of TOS. Patient's symptoms, clinical examination and duplex ultrasonography usually suffice in deciding patient's management. Our proposed treatment strategies are based on the Scher classification. The choice of the procedure and approach should depend on surgeon's experience and need for arterial reconstruction. PMID- 27668337 TI - Simple and effective reverse bent wiring technique for side branch access after crush stenting. PMID- 27668338 TI - ST-elevation myocardial infarction due to spontaneous coronary artery dissection: to touch or not to touch? The conundrum of invasive versus conservative treatment. PMID- 27668339 TI - The worsening renal failure in a chronic cardio-renal syndrome type II: efficacy of a single levosimendan infusion. PMID- 27668340 TI - A myocardial infarction in a patient with previous myocardial revascularization presenting with tachyarrhythmia. Is it type 1, 2 or 4c myocardial infarction? PMID- 27668341 TI - Symptomatic in-stent restenosis due to complete stent fracture treated with drug coated balloon. PMID- 27668342 TI - Left internal mammary artery graft stenosis and post-angioplasty restenosis: follow-up through multi-slice cardiac computed tomography angiography. PMID- 27668343 TI - Left main coronary artery thrombosis with distal coronary embolization in a patient with methyltetrahydrofolate reductase C677T mutation presenting with STEMI. PMID- 27668344 TI - Ultrastructural Assessment of 2-(acridin-9-ylmethylene)-N phenylhydrazinecarbothioamide activity on human breast adenocarcinoma cells. AB - The aim of the present study was to investigate ultrastructural changes induced by (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (APHCA) treatment on human breast adenocarcinoma cancer cells MCF-7, besides the evaluation of phosphatidylserine externalization and DNA fragmentation in treated cells. Cell viability analysis demonstrated concentration and time-manner cytotoxicity. Treated MCF-7 cells did not expose phosphatidylserine residues to the external plasma membrane surface and DNA fragmentation was not visualized by electrophoresis. Light microscopy showed compromised cell density and presence of vacuolization after APHCA treatment with 60MUM. Scanning and transmission electron microscopies revealed hallmarks of autophagy, namely the presence of membrane bebbling and autophagosomes, besides shrunken cells and cell debris in treated MCF-7 cells. However, more specific tests such as the quantification of mammalian autophagy proteins are necessary to determine the kind of death that is trigged by APHCA. PMID- 27668345 TI - Molecular dynamics investigation on structural and transport properties of p7 ion channel. PMID- 27668346 TI - Transport of haloacids across biological membranes. AB - Haloacids are considered to be environmental pollutants, but some of them have also been tested in clinical research. The way that haloacids are transported across biological membranes is important for both biodegradation and drug delivery purposes. In this review, we will first summarize putative haloacids transporters and the information about haloacids transport when studying carboxylates transporters. We will then introduce MCT1 and SLC5A8, which are respective transporter for antitumor agent 3-bromopyruvic acid and dichloroacetic acid, and monochloroacetic acid transporters Deh4p and Dehp2 from a haloacids degrading bacterium. Phylogenetic analysis of these haloacids transporters and other monocarboxylate transporters reveals their evolutionary relationships. Haloacids transporters are not studied to the extent that they deserve compared with their great application potentials, thus future inter-discipline research are desired to better characterize their transport mechanisms for potential applications in both environmental and clinical fields. PMID- 27668347 TI - An Examination of United States Air Force Suicide Decedents Based on Documented Suicide Attempt Histories. AB - In this study, we compared United States military decedents who died by suicide on their first attempt with decedents who had made multiple attempts. Death investigation files for 217 United States Air Force (USAF) personnel who died by suicide between 1996 and 2006 were coded for demographic, psychosocial, and psychiatric characteristics. Among USAF suicide decedents, 77% died by suicide on their first attempt and 23% had a documented history of at least one prior attempt. Decedents with a history of prior attempts were more likely to have an interpersonal stressor within 3 months of death and were twice as likely to have a documented Axis I diagnosis. There were few differences between military suicide decedents based on history of prior attempts. Further research is needed to inform military suicide prevention endeavors. PMID- 27668350 TI - Commentary on Weiss. PMID- 27668348 TI - Assessing the modified receptive field (MRF) theory: Evidence from Sinhalese English bilinguals. AB - The current study aimed to test the applicability of the modified receptive field (MRF) theory (Tydgat & Grainger, 2009) with English native speakers (Experiment 1) and Sinhalese native speakers (Experiment 2), who were skilled readers of both Sinhala and Roman scripts. A two-alternative forced choice (2AFC) procedure to measure identification accuracy for all positions in a string of five characters, which consisted of Roman script letters, Sinhala letters or symbols was conducted. For Roman script, the English and Sinhalese speakers displayed analogous results as in previous studies for Roman letters and symbols (i.e., an initial letter advantage and W-shaped function for Roman letters and a Lambda shaped function for symbols). In contrast for Sinhala script, the Sinhalese speakers displayed a strong linear function with accuracy for letter positions 1, 2 and 3 similarly advantaged. We propose that this characteristic pattern for Sinhala script has developed as a specialised adaptive mechanism to optimise the processing of letters when reading in this distinctive script. PMID- 27668349 TI - Intensive Clinical and Subjective Studies. PMID- 27668351 TI - Study of association between pre-senile cataracts and rs11615 of ERCC1, rs13181 of ERCC2, and rs25487 of XRCC1 polymorphisms in a Spanish population. AB - BACKGROUND: The purpose of this study was to attempt to determine if the presence of certain polymorphisms in the DNA repair genes (ERCC1, ERCC2, and XRCC1) is associated with pre-senile cataract development. MATERIALS AND METHODS: We performed a retrospective study over three groups of patients. The first group with pre-senile cataract was formed by 72 patients younger than 55 years with cataract surgery. The second group with senile cataract was formed by 101 patients older than 55 years with cataract surgery. And the third group, without cataract, was formed by 42 subjects older than 55 years without lens opacities. We analyzed the presence of SNP rs11615 from ERCC1, rs13181 from ERCC2, and rs25487 from XRCC1 and the relationship between risk factors such as smoking, alcohol intake, hypertension, and diabetes. RESULTS: The comparison of the genotype distribution in ERCC1 and ERCC2 did not show any statistically significant association in any of our analyses (p > 0.05). The comparison of the genotype distribution in XRCC1 within the different groups did not show any statistically significant associations (p > 0.05), except for the comparison between the pre-senile cataract group and the group without cataract, where an increased risk of developing pre-senile cataract for the genotype Gln/Gln (p = 0.029; OR = 1.02-40.67) in recessive inheritance models was observed when adjusting for risk factors. CONCLUSIONS: Allelic variants in ERCC1 and ERCC2 are not associated with an increased risk of developing pre-senile cataract. The presence of Gln/Gln in XRCC1 in the pre-senile cataract group with regard to the group without cataract is associated with a major risk of developing pre-senile cataract. PMID- 27668352 TI - Implementing Effective Policy in a National Mental Health Reengagement Program for Veterans. AB - Policy is a powerful motivator of clinical change, but implementation success can depend on organizational characteristics. This article used validated measures of organizational resources, culture, and climate to predict uptake of a nationwide Veteran's Health Administration (VA) policy aimed at implementing Re-Engage, a brief care management program that reestablishes contact with veterans with serious mental illness lost to care. Patient care databases were used to identify 2738 veterans lost to care. Local recovery coordinators (LRCs) were to update disposition for 2738 veterans at 158 VA facilities and, as appropriate, facilitate a return to care. Multivariable regression was used to assess organizational culture and climate as predictors of early policy compliance (via LRC presence) and uptake at 6 months. Higher composite climate and culture scores were associated with higher odds of having a designated LRC but were not predictive of higher uptake. Sites with LRCs had significantly higher rates of updated documentation than sites without LRCs. PMID- 27668353 TI - The Role of Metacognitive Self-Reflectivity in Emotional Awareness and Subjective Indices of Recovery in Schizophrenia. AB - Emotional awareness deficits in people with schizophrenia have been linked to poorer objective outcomes, but no work has investigated the relationship between emotional awareness and subjective recovery indices or metacognitive self reflectivity. The authors hypothesized that increased emotional awareness would be associated with greater self-esteem, hope, and self-reflectivity and that self reflectivity would moderate links between emotional awareness and self-esteem and hope-such that significant relationships would only be observed at lower levels of self-reflectivity. Participants were 56 people with schizophrenia spectrum disorders. Correlations revealed that better emotional awareness was significantly associated with increased self-esteem and hope but not self reflectivity. Self-reflectivity moderated the relationship between emotional awareness and self-esteem but not hope. Overall, findings suggest that emotional awareness may affect self-esteem for those low in self-reflectivity, but other factors may be important for those with greater self-reflectivity. Results emphasize the importance of interventions tailored to enhance self-reflective capacity in clients with schizophrenia. PMID- 27668354 TI - Methylation Status of the Serotonin Transporter Promoter CpG Island Is Associated With Major Depressive Disorder in Chinese Han Population: A Case-Control Study. AB - This study was aimed to investigate the relationship between the methylation status of serotonin transporter (5-HTT) and major depressive disorder (MDD) in Chinese Han population. A total of 96 patients with MDD and 55 healthy volunteers were recruited, and the methylation index (MtI) at six positions in the cytosine phosphate-guanosine island of 5-HTT gene was measured for each subject using bisulfite pyrosequencing. MtIs at positions 5 and 6 were higher in patients with MDD than those in controls. According to the multivariable logistic regression analysis, MtIs at positions 4 and 5 were significantly associated with MDD. Besides, depression education was an independent risk factor, whereas higher educational levels were protective factors for MDD. In addition, positions 1 and 4 were negatively correlated with weight and diurnal variation. Therefore, 5-HTT methylation might be closely related with MDD in Chinese Han population because of the correlation with diurnal variation and weight. PMID- 27668355 TI - Patient, Therapist, and System Factors Influencing the Effectiveness of Prolonged Exposure for Veterans With Comorbid Posttraumatic Stress Disorder and Traumatic Brain Injury. AB - In contrast to concerns that cognitive limitations and neurobehavioral symptoms (NBS) associated with traumatic brain injury (TBI) may inhibit treatment effectiveness, a recent study found prolonged exposure (PE) led to large reductions in posttraumatic stress disorder (PTSD) symptoms among Iraq Afghanistan veterans with a range of TBI severity (article by Wolf, Kretzmer, Crawford, Thors, Wagner, Strom, Eftekhari, Klenk, Hayward, and Vanderploeg [J Trauma Stress 28:339-347, 2015]). We further examined this sample of 69 veterans to determine whether system, veteran, and therapist factors predicted clinically significant responses. Results of hierarchical, logistic regressions revealed that therapist training in PE and lower service connection were associated with increased odds of large decreases in PTSD symptoms after adjusting for the robust effect of PE sessions completed. Other patient-level factors including age, time since injury, and baseline NBS were unrelated to significant improvements. Findings emphasized the impact of PE dosage, indicated greater mastery of the protocol was beneficial, and showed that service connection could impede self reported, clinically significant change during PE in this important cohort. PMID- 27668356 TI - Cortical sources of resting state EEG rhythms are related to brain hypometabolism in subjects with Alzheimer's disease: an EEG-PET study. AB - Cortical sources of resting state electroencephalographic (EEG) delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms show abnormal activity (i.e., current density) in patients with dementia due to Alzheimer's disease (AD). Here, we hypothesized that abnormality of this activity is related to relevant disease processes as revealed by cortical hypometabolism typically observed in AD patients by fluorodeoxyglucose positron emission tomography. Resting state eyes closed EEG data were recorded in 19 AD patients with dementia and 40 healthy elderly (Nold) subjects. EEG frequency bands of interest were delta and low frequency alpha. EEG sources were estimated in these bands by low-resolution brain electromagnetic tomography (LORETA). Fluorodeoxyglucose positron emission tomography images were recorded only in the AD patients, and cortical hypometabolism was indexed by the so-called Alzheimer's discrimination analysis tool (PALZ) in the frontal association, ventromedial frontal, temporoparietal association, posterior cingulate, and precuneus areas. Results showed that compared with the Nold group, the AD group pointed to higher activity of delta sources and lower activity of low-frequency alpha sources in a cortical region of interest formed by all cortical areas of the PALZ score. In the AD patients, there was a positive correlation between the PALZ score and the activity of delta sources in the cortical region of interest (p < 0.05). These results suggest a relationship between resting state cortical hypometabolism and synchronization of cortical neurons at delta rhythms in AD patients with dementia. PMID- 27668358 TI - The effect of surface nano-corrugation on the squeeze-out of molecular thin hydrocarbon films between curved surfaces with long range elasticity. AB - The properties of linear alkane lubricants confined between two approaching solids are investigated by a model that accounts for the roughness, curvature and elastic properties of the solid surfaces. We consider linear alkanes of different chain lengths from [Formula: see text] to [Formula: see text], confined between corrugated solid walls. The pressure necessary to squeeze out the lubricant increases rapidly with the alkane chain length, but is always much lower than in the case of smooth surfaces. The longest alkanes form domains of ordered chains and the squeeze-out appears to nucleate in the more disordered regions between these domains. The short alkanes stay fluid-like during the entire squeeze out process which result in a very small squeeze-out pressure which is almost constant during the squeeze-out of the last monolayer of the fluid. In all cases we observe lubricant trapped in the valley of the surface roughness, which cannot be removed independent of the magnitude of the squeezing pressures. PMID- 27668357 TI - Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-analysis. AB - Importance: Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies characterized by predominant involvement of the optic nerves and spinal cord. In most patients, an IgG autoantibody binding to astrocytic aquaporin 4, the principal water channel of the central nervous system, is detected. Rituximab, a chimeric monoclonal antibody specific for the CD20 B lymphocyte surface antigen, has been increasingly adopted as a first-line off label treatment for patients with NMOSDs. Objective: To perform a systematic review and a meta-analysis of the efficacy and safety of rituximab use in NMOSDs, considering the potential predictive factors related to patient response to rituximab in this disease. Evidence Review: English-language studies published between January 1, 2000, and July 31, 2015, were searched in the MEDLINE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov databases. Patient characteristics, outcome measures, treatment regimens, and recorded adverse effects were extracted. Findings: Forty-six studies were included in the systematic review. Twenty-five studies that included 2 or more patients with NMOSDs treated with rituximab were included in the meta-analysis. Differences in the annualized relapse rate ratio and Expanded Disability Status Scale score before and after rituximab therapy were the main efficacy measures. Safety outcomes included the proportion of deaths, withdrawals because of toxic effects, and adverse effects. Results: Among 46 studies involving 438 patients (381 female and 56 male [sex was not specified in 1 patient]; mean age at the outset of treatment, 32 years [age range, 2-77 years]), rituximab therapy resulted in a mean (SE) 0.79 (0.15) (95% CI, -1.08 to -0.49) reduction in the mean annualized relapse rate ratio and a mean (SE) 0.64 (0.27) (95% CI, -1.18 to -0.10) reduction in the mean Expanded Disability Status Scale score. A significant correlation was observed between disease duration and the Expanded Disability Status Scale score. Adverse effects were recorded in 114 of 438 (26%) patients treated with rituximab. Specifically, 45 patients (10.3%) experienced infusion-related adverse effects, 40 patients (9.1%) had an infection, 20 patients (4.6%) developed persistent leukopenia, 2 patients (0.5%) were diagnosed as having posterior reversible encephalopathy, and 7 patients (1.6%) died. Conclusions and Relevance: This systematic review and meta-analysis provides evidence that rituximab therapy reduces the frequency of NMOSD relapses and neurological disability in patients with NMOSDs. However, the safety profile suggests caution in prescribing rituximab as a first-line therapy. PMID- 27668359 TI - Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index-Reply. PMID- 27668360 TI - A competitive trade-off limits the selective advantage of increased antibiotic production. AB - In structured environments, antibiotic-producing microorganisms can gain a selective advantage by inhibiting nearby competing species1. However, despite their genetic potential2,3, natural isolates often make only small amounts of antibiotics, and laboratory evolution can lead to loss rather than enhancement of antibiotic production4. Here, we show that, due to competition with antibiotic resistant cheater cells, increased levels of antibiotic production can actually decrease the selective advantage to producers. Competing fluorescently labelled Escherichia coli colicin producers with non-producing resistant and sensitive strains on solid media, we found that although producer colonies can greatly benefit from the inhibition of nearby sensitive colonies, this benefit is shared with resistant colonies growing in their vicinity. A simple model, which accounts for such local competitive and inhibitory interactions, suggests that the advantage of producers varies non-monotonically with the amount of production. Indeed, experimentally varying the amount of production shows a peak in selection for producers, reflecting a trade-off between benefit gained by inhibiting sensitive competitors and loss due to an increased contribution to resistant cheater colonies. These results help explain the low level of antibiotic production observed for natural species and can help direct laboratory evolution experiments selecting for increased or novel production of antibiotics. PMID- 27668361 TI - Vital Directions for US Health Care: Big Ideas on Small Signposts With Mixed Signals. PMID- 27668363 TI - Response to "The Evidence Behind Integrating Palliative Care Into Oncology Practice"?. AB - I am writing in response to "The Evidence Behind Integrating Palliative Care Into Oncology Practice" (Dailey, 2016). I have 16 years of oncology experience and work at the University Health Systems in San Antonio, Texas. Our facility's palliative care program holds the Advanced Certification awarded by the Joint Commission, and we have dedicated inpatient beds for palliative care patients. PMID- 27668362 TI - After the Bell: Lifestyle Transformation After Cancer Treatment. AB - There are many traditions on the last day of chemotherapy. It is often a happy time when patients have pictures taken with their oncology nurses and ring the bell as they leave the infusion area. For many, the bell is symbolic of the completion of cancer treatment and the beginning of the rest of their lives as cancer survivors. After the bell, survivors often go home wondering what they can do to be healthier and reduce their risk of recurrence.? PMID- 27668364 TI - Potential Benefits of Oral Cryotherapy for Chemotherapy-Induced Mucositis. AB - Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5 fluorouracil [Adrucil(r)] and melphalan [Alkeran(r)]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.? PMID- 27668365 TI - A Multidisciplinary Approach to Standardizing Processes for Blinatumomab Administration. AB - Blinatumomab (Blincyto(r)) has received accelerated approval for treatment of relapsed or refractory acute lymphoblastic leukemia. This article describes the authors' experience with a multidisciplinary collaboration among nursing, pharmacy, prescribers, and support staff, which has proven to be key for safe administration. The approach can be applied to other institutions planning to use blinatumomab. PMID- 27668366 TI - Using Technology to Give Patients a Voice After Surgery for Head and Neck Cancer. AB - For patients with head and neck cancer, altered communication is a frequently occurring and highly upsetting issue that has been associated with psychological distress, fear, and anger among those with temporary or permanent speech impairment postsurgery. Many postoperative patients express that the most terrifying situation is to wake up from surgery and not be able to speak. Mobile devices have become part of everyday life, and augmentative and alternative communication mobile applications have the potential to enhance the healthcare journey of the patient and provider.? PMID- 27668367 TI - Big Data and Pharmacovigilance: The Role of Oncology Nurses. AB - When new anticancer medications are approved, their safety profiles are often not fully understood. Oncology nurses have a responsibility to file reports of adverse drug events with safety registries such as MedWatch. If these registries receive prompt, complete, and accurate data from clinicians, agencies such as the U.S. Food and Drug Administration will have a stronger ability to detect hazards and to issue safety recommendations.?. PMID- 27668368 TI - Addressing Disparities: The Alliance Breast Cancer Community-Based Program for Hispanic Women. AB - BACKGROUND: The Alliance Breast Cancer (ABC) program is a community-based initiative developed and implemented to address the needs of Hispanic women faced with a cancer diagnosis or cancer survivorship issues. OBJECTIVES: This article evaluates the effectiveness of a community effort to address breast cancer related disparities among Hispanic women. METHODS: Nurse scientists collaborated with program staff to conduct a systematic five-year program evaluation. Data sources included monthly and annual reports, participant tracking databases, and an annual satisfaction survey. FINDINGS: Hispanic breast cancer survivors who participated in the program expressed feeling very satisfied with the services and believe that it addresses the specific barriers faced by this population. The ABC program serves as a best practice example to other communities forging partnerships to address health disparities and community needs in a culturally tailored manner. PMID- 27668369 TI - Evaluation of Employee Vaccination Policies in Outpatient Oncology Clinics: A Pilot Study. AB - BACKGROUND: All major hospital facilities in the state of Utah have employee vaccination policies. However, the presence of healthcare worker vaccination policies in outpatient oncology clinics was unknown. OBJECTIVES: The objectives of this article are to identify oncology outpatient employee vaccination policies in Utah and to identify what consequences, if any, are present for unvaccinated employees. METHODS: This was a cross-sectional, descriptive study design in which clinic managers from outpatient oncology clinics were asked, via questionnaire, to describe the clinic's employee vaccination policy and the consequences for refusing the policy. FINDINGS: Most vaccination policies applied to employees primarily assigned to work in the direct patient care area. Most commonly, influenza and hepatitis B vaccines were required as part of the vaccination policy. Most managers offered free vaccinations to employees, but most managers also allowed employees to refuse to follow the vaccination policy for medical, religious, or personal reasons. PMID- 27668370 TI - Computer-Based Cognitive Training for Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors. AB - BACKGROUND: Advancements in chemotherapy have greatly increased breast cancer survival, leading to an increased focus on the management of long-term effects of treatment. Chemotherapy-related cognitive impairment, one such long-term effect, is experienced by as many as 90% of breast cancer survivors (BCS) and negatively affects employment, daily function, and quality of life. Chemotherapy-related cognitive impairment is a top research and clinical practice priority. OBJECTIVES: The aim of this article is to review computer-based cognitive training intervention studies tested in BCS, present implications for practice and directions for future research, and discuss neuroplasticity and cognitive reserve, the mechanisms by which computer-based cognitive training produces physiologic changes in the brain. METHODS: A search of PubMed, CINAHL(r), and PsycINFO(r) databases yielded two computer-based cognitive training intervention studies in BCS. FINDINGS: This review suggests that computer-based cognitive training may enhance cognitive function in BCS with chemotherapy-related cognitive impairment. Oncology nurses are in a unique position to support BCS experiencing chemotherapy-related cognitive impairment. In addition to acknowledging BCS' concerns, screening for other potential factors, and providing education on healthy living, nurses may suggest computer-based cognitive training as an approach to managing chemotherapy-related cognitive impairment. Future research should use imaging and larger populations. PMID- 27668371 TI - Comparing Self-Injection Teaching Strategies for Patients With Breast Cancer and Their Caregivers: A Pilot Study. AB - BACKGROUND: A prospective, quasiexperimental pilot study with a sequential design was performed to compare two methods of teaching self-injection. OBJECTIVES: The study examined 50 patients with breast cancer undergoing adjuvant or neoadjuvant treatment and their caregivers to determine if simulation during the teaching experience affects patient/caregiver satisfaction, worry, and self-confidence, as well as nurse satisfaction. METHODS: Structured questionnaires were administered before the teaching, immediately after the teaching, and after the injection was performed at home. Nurses who performed the teaching also completed a questionnaire after the teaching. FINDINGS: Use of simulation did not affect patient/caregiver satisfaction, worry, or self-confidence. The largest impact on learner worry was the actual teaching experience, regardless of the methodology used. Nurses reported greater levels of satisfaction when simulation was part of the teaching. Patient/caregiver satisfaction with the teaching experience decreased after performing the injection at home. Additional research is needed to identify the best methodology for teaching patients and caregivers self injection. Data from this study revealed that the addition of simulation during teaching does not always translate to better education. In addition, based on patient/caregiver reports, no substitution exists for actual injection administration. PMID- 27668372 TI - Impact of an Alert System on Quality Indicators in Patients With Acute Promyelocytic Leukemia. AB - BACKGROUND: Acute promyelocytic leukemia (APL), once the most lethal form of adult acute leukemia, has become the most curable. The goal of early and well managed treatment induction is to reduce the malignant burden of promyelocytes to below the cytologically detectable level. OBJECTIVES: Oncology nurses who care for patients with APL need to be acutely aware of the basic differences in this disease from other forms of leukemia, including the two main complications for the newly diagnosed patient. METHODS: This article will briefly review APL and its associated presenting symptoms, prognosis, treatment, and complications. FINDINGS: These complications require immediate activation of expert staff and resources to protect critically ill patients with APL from associated morbidity and mortality. PMID- 27668373 TI - Nursing Management of Cutaneous Toxicities From Epidermal Growth Factor Receptor Inhibitors. AB - BACKGROUND: Personalized targeted therapies have become an emerging paradigm in cancer treatment. Although generally more tolerable than other chemotherapeutic agents, one therapy, epidermal growth factor receptor inhibitors (EGFRIs), commonly results in the formation of cutaneous toxicities, which can negatively affect patients' treatment adherence and quality of life. OBJECTIVES: The aim of this article is to review nursing management strategies for EGFRI-related cutaneous toxicities. METHODS: A systematic literature review was performed, including database searches in PubMed/MEDLINE(r), CINAHL(r), Cochrane Library, PsycINFO(r), and Web of Science. FINDINGS: Nurses are essential to the management of EGFRI-related cutaneous toxicities and are in an ideal position to provide supportive care throughout the course of the EGFRI treatment. The aim of nursing management is to maintain patients' treatment adherence and quality of life by employing a preemptive and proactive approach. Patient education is the most frequently reported management strategy. However, treatment options and management strategies are largely anecdotal and based on individual reports and expert opinions. Although no evidence-based management strategies exist, nurses can rely on existing assessment tools and guidelines to provide patients with symptom management and supportive care. PMID- 27668374 TI - Genomic Variants Associated With Cancer-Related Fatigue: A Systematic Review. AB - BACKGROUND: Cancer-related fatigue (CRF) is the most common stressful side effect caused by cancer and cancer treatments. Although CRF causes a significant burden to quality of life, no pharmacologic interventions are available because the mechanism remains unknown. OBJECTIVES: This systematic review analyzed the genomic variants that have been found to be associated with CRF. METHODS: A search for peer-reviewed articles through PubMed, EBSCOhost, and DePaul WorldCat Libraries Worldwide yielded 16 published studies. FINDINGS: The majority of genomic variants demonstrated that the inflammatory and immune response pathways, including the neuro-proinflammatory cytokine pathway, have statistically significant associations with CRF. Additional genomic studies are still needed to validate the findings in this systematic review. The exact biologic underpinnings that contribute to the development of CRF remain unknown. PMID- 27668375 TI - Using Relaxation and Guided Imagery to Address Pain, Fatigue, and Sleep Disturbances: A Pilot Study. AB - BACKGROUND: Few studies have been conducted on the use of patient-controlled relaxation and guided imagery interventions for the symptom cluster of pain, fatigue, and sleep disturbance during cancer treatment. OBJECTIVES: The primary aim of this study was to evaluate the feasibility, acceptability, and participant satisfaction with use of patient-controlled relaxation and/or imagery interventions for pain, fatigue, and sleep disturbance. A secondary aim was to examine the data for trends in pain, fatigue, and sleep improvement because of the effects of relaxation and guided imagery. METHODS: Twelve adult patients with cancer were randomized to one of four groups. FINDINGS: Patients reported a high degree of satisfaction with the relaxation and guided imagery interventions. Patients in the relaxation and guided imagery or combined groups showed a trend toward improvement in fatigue and sleep disturbance scores. Pain remained a problem for the majority of patients. Difficulties in recruiting participants resulted in an insufficient sample size for generalizable findings. With hospital environments tending to be noisy, relaxation and guided imagery may facilitate rest and sleep for hospitalized patients. An examination of individual scores showed a trend toward improvement in sleep quality. PMID- 27668376 TI - Benefits and Risks of Fosaprepitant in Patients Receiving Emetogenic Regimens. AB - Fosaprepitant dimeglumine (Emend IV(r)) is an IV antiemetic that may be beneficial to patients receiving highly emetogenic regimens. Aprepitant (Emend(r)) is an oral medication that is administered for three consecutive days, whereas fosaprepitant is a single-dose IV medication that is administered on the day of chemotherapy for 20-30 minutes (depending on the IV access type). Fosaprepitant may be useful, yet it can also present a risk for hypersensitivity reactions and phlebitis. Oncology nurses must be aware of the signs and symptoms of these potential adverse events to properly care for their patients. PMID- 27668377 TI - Development and Evaluation of a Lung Cancer Screening Decision Aid. AB - Lung cancer is the second most common cancer; however, it often is not diagnosed until the advanced stages. Early-stage lung cancer is curable, but screening tools are not usually implemented in practice because of a lack of provider awareness. A lung cancer screening decision aid may increase screening use and, ultimately, reduce lung cancer deaths.? PMID- 27668378 TI - Oncology Nursing and Shared Decision Making for Cancer Treatment. AB - This study aimed to describe the contemporary role of the oncology nurse throughout the entire cancer shared decision-making (SDM) process. Study participants consisted of 30 nurses and nurse practitioners who are actively involved in direct care of patients with cancer in the inpatient or outpatient setting. The major themes that emerged from the content analysis are: oncology nurses have various roles at different time points and settings of cancer SDM processes; patient education, advocacy, and treatment side effects management are among the top nursing roles; oncology nurses value their participation in the cancer SDM process; oncology nurses believe they have a voice, but with various degrees of influence in actual treatment decisions; nurses' level of disease knowledge influences the degree of participation in cancer SDM; and the nursing role during cancer SDM can be complicated and requires flexibility.?. PMID- 27668379 TI - Healing My Whole Self. AB - Surviving cancer was the beginning of a long journey to healing my whole self. When I was first diagnosed with breast cancer, I was 39 years old. I had spent most of my life working in a number of high-stress communications positions in Massachusetts and had recently become the press secretary for Boston's mayor, the Honorable Thomas M. Menino. On day one, I had to tell my new boss that I would need to step down and help him find a replacement because I had cancer. It was an extremely difficult time personally and professionally, but the mayor insisted that I stay. He was gracious and positive, telling me I would get through this and not to give up. On the outside, I did my best to keep it together, but my internal voice said otherwise.?. PMID- 27668380 TI - When "No" Is Not an Acceptable Answer for Treatment. AB - The focus of health care has moved toward prevention, and insurance companies are supporting preventive practices that enable their members to remain healthy. Many insurance companies have recorded healthy tips delivered by phone, employed case managers to assist patients in keeping physician appointments, created dedicated hot lines staffed by nurses, and developed resource centers. However, specific instances arise when insurance companies do not allow patients to have certain procedures because of contract language that was previously negotiated between the employer or individual and the insurance company. This was the case for my patient.?. PMID- 27668381 TI - Quality of Life, Psychological Burden, and Sleep Quality in Patients With Brain Metastasis Undergoing Whole Brain Radiation Therapy. AB - BACKGROUND: Patients with brain metastasis (BM) usually suffer from poor quality of life (QOL), anxiety, depression, and sleep disorders in their reduced lifespan. OBJECTIVES: The aim of this study was to evaluate QOL, anxiety, depression, and sleep characteristics in patients with BM at the beginning and end of whole brain radiation therapy (WBRT) and three months after treatment. METHODS: Thirty-three patients undergoing WBRT for BM were featured in this study. The authors used the Karnofsky Performance Status (KPS) scale to measure performance status, the Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and depression, the SF-36(r) to evaluate health-related QOL, and the Pittsburgh Sleep Quality Index to evaluate sleep disorders at the start of WBRT, the end of WBRT, and three months after WBRT. FINDINGS: Statistically significant improvements were noted in KPS scores from baseline evaluation to the end of WBRT and to three months after WBRT. No significant differences were observed in SF-36 and HADS scores between the start and the end of WBRT. Anxiety scores were negatively correlated with survival at the end of WBRT. Overall survival was better in those who reported better sleep. WBRT improves KPS scores and does not worsen sleep quality or mood, even in patients with poor performance status. When changes in mood and sleep quality are observed, survival and QOL may improve in patients with BM; consequently, nurses should be responsive to these changes. PMID- 27668382 TI - Significance of Nonphysical Predictors of Distress in Cancer Survivors. AB - BACKGROUND: The Distress Thermometer (DT) is a well-validated tool that is frequently used in patients with cancer to screen for general distress and to generate referrals. However, a majority of the DT problem list items relate to physical concerns; this may lead to psychosocial issues being overshadowed. OBJECTIVES: The purpose of the current study is to examine the endorsement rates for nonphysical items, as well as the relationship between these items and overall DT scores. METHODS: A multiple logistic regression analysis of the first time distress rating scale of 1,209 patients from 2005-2009 was conducted to determine whether nonphysical items on the DT significantly contributed to a patient falling into one of two categories. FINDINGS: This study provides evidence that emotional variables are particularly significant for patients who are at risk for distress and, consequently, should be prioritized for intervention when endorsed on the DT problem list. PMID- 27668384 TI - Improving Awareness, Identification, and Management of Sarcopenic Obesity in Cancer Survivors: An Evidence-Based Toolbox. AB - BACKGROUND: Sarcopenic obesity, the dual condition of decreased muscle mass with increased fat mass, can affect morbidity, mortality, and quality of life in adult cancer survivors. OBJECTIVES: The purpose of this project was to determine the effects of the use of an educational toolbox on advanced practice nurses' (APNs') confidence in identifying and managing adult cancer survivors at risk for sarcopenic obesity. METHODS: APNs in an outpatient practice who care for adult cancer survivors received an educational toolbox with strategies to identify and manage adult cancer survivors at risk for sarcopenic obesity. FINDINGS: APNs reported being more confident in their ability to identify adult patients with cancer at risk for sarcopenic obesity and in their ability to manage these patients compared to prior to the intervention. Educational resources provided an effective tool for identifying and managing patients at risk for sarcopenic obesity. PMID- 27668383 TI - Validation of Predictors of Fall Events in Hospitalized Patients With Cancer. AB - BACKGROUND: A seven-item cancer-specific fall risk tool (Cleveland Clinic Capone Albert [CC-CA] Fall Risk Score) was shown to have a strong concordance index for predicting falls; however, validation of the model is needed. OBJECTIVES: The aims of this study were to validate that the CC-CA Fall Risk Score, made up of six factors, predicts falls in patients with cancer and to determine if the CC-CA Fall Risk Score performs better than the Morse Fall Tool. METHODS: Using a prospective, comparative methodology, data were collected from electronic health records of patients hospitalized for cancer care in four hospitals. Risk factors from each tool were recorded, when applicable. Multivariable models were created to predict the probability of a fall. A concordance index for each fall tool was calculated. FINDINGS: The CC-CA Fall Risk Score provided higher discrimination than the Morse Fall Tool in predicting fall events in patients hospitalized for cancer management. PMID- 27668385 TI - Optune(r): Practical Nursing Applications. AB - BACKGROUND: After receiving U.S. Food and Drug Administration approval for the treatment of newly diagnosed glioblastoma (GBM) in 2015, following initial approval for treatment of recurrent GBM in 2011, Optune(r), a device that uses tumor-treating fields (TTFields) therapy, continues to gain acceptance in the practice environment. OBJECTIVES: This article reviews how TTFields differ from traditional GBM treatment approaches and discusses the pivotal role nurses play in helping patients successfully use this therapy. This includes the importance of adherence to daily continuous therapy because adherence optimizes patient outcomes. METHODS: This article provides oncology nurses with practical guidance to share with patients who are candidates for treatment with TTFields, as well as information to facilitate patients' understanding of the use of Optune and how best to incorporate it into their activities of daily living. FINDINGS: Nurses are key members of the multidisciplinary treatment team that manages patients with GBM. Therefore, oncology nurses are well equipped to educate patients and caregivers about the use of and benefits of adherence to TTFields. PMID- 27668387 TI - Rationale and Background on Tumor-Treating Fields for Glioblastoma. AB - BACKGROUND: More than 150 years after the first description of glioma cells, patients with glioblastoma (GBM) continue to have a poor prognosis despite standard-of-care therapy. With the introduction of tumor-treating fields (TTFields) therapy for the treatment of recurrent GBM in 2011 and for newly diagnosed GBM in 2015, the opportunity to increase progression-free survival and overall survival while improving quality of life provides a welcome option. OBJECTIVES: This article describes how TTFields therapy may be used in the treatment of patients with recurrent GBM. METHODS: This article provides oncology nurses with two case studies that examine how TTFields therapy can be integrated into the overall treatment paradigm. FINDINGS: These two patient case studies demonstrate the autonomy and lack of adverse effects that TTFields therapy offers to patients with GBM. PMID- 27668386 TI - Glioblastoma: Overview of Disease and Treatment. AB - BACKGROUND: Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Current treatment options at diagnosis are multimodal and include surgical resection, radiation, and chemotherapy. Significant advances in the understanding of the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies for recurrent and newly diagnosed disease. Innovative treatments, such as tumor-treating fields (TTFields) and immunotherapy, give hope for enhanced survival. OBJECTIVES: This article reviews the background, risks, common complications, and treatment options for GBM. METHODS: A brief review of GBM, treatment options, and a look at new therapies that have been approved for new and recurrent disease are included in this article. FINDINGS: Despite aggressive resection and combined modality adjuvant treatment, most GBMs recur. Treatments, such as TTFields, drugs to target molecular receptors, and immunotherapy, are promising new options. PMID- 27668388 TI - Efficacy and Safety of Treating Glioblastoma With Tumor-Treating Fields Therapy. AB - BACKGROUND: Glioblastoma (GBM) is a highly aggressive astrocytoma with a dismal prognosis. Since 1976, only three chemotherapeutic agents have been approved for the treatment of GBM. Tumor-treating fields (TTFields) therapy, delivered via a noninvasive device, is a new therapy approved for use in patients with recurrent GBM and in combination with temozolomide for the treatment of newly diagnosed GBM. OBJECTIVES: This article reviews the mechanism of action and findings from preclinical and clinical studies supporting the use of TTFields for patients with newly diagnosed and recurrent GBM. METHODS: This article provides an overview of published literature on the efficacy and safety of treating GBM with TTFields. FINDINGS: For the first time in more than a decade, patients with GBM have a noninvasive treatment option that has been shown to increase progression-free survival and overall survival with minimal adverse events. PMID- 27668391 TI - Reframing US Maternity Care: Lessons Learned From End-of-Life Care. PMID- 27668392 TI - Research Into Brain Disorders as an Example of Targeted Science. PMID- 27668390 TI - MeCP2 and histone deacetylases 1 and 2 in dorsal striatum collectively suppress repetitive behaviors. AB - Class I histone deacetylases (HDACs) Hdac1 and Hdac2 can associate together in protein complexes with transcriptional factors such as methyl-CpG-binding protein 2 (MeCP2). Given their high degree of sequence identity, we examined whether Hdac1 and Hdac2 were functionally redundant in mature mouse brain. We demonstrate that postnatal forebrain-specific deletion of both Hdac1 and Hdac2 in mice impacts neuronal survival and results in an excessive grooming phenotype caused by dysregulation of Sap90/Psd95-associated protein 3 (Sapap3; also known as Dlgap3) in striatum. Moreover, Hdac1- and Hdac2-dependent regulation of Sapap3 expression requires MECP2, the gene involved in the pathophysiology of Rett syndrome. We show that postnatal forebrain-specific deletion of Mecp2 causes excessive grooming, which is rescued by restoring striatal Sapap3 expression. Our results provide new insight into the upstream regulation of Sapap3 and establish the essential role of striatal Hdac1, Hdac2 and MeCP2 for suppression of repetitive behaviors. PMID- 27668393 TI - Sensitivity of Follow-Up Methods in Patients After Fertility-Sparing Surgery for Cervical Cancers. AB - OBJECTIVE: The aim of our study was to compare the sensitivity of various methods and their combinations in the follow-up of patients with cervical cancer after fertility-sparing surgery (FSS). METHODS: Included were women with cervical cancer in stages IA2 to IB2 who underwent FSS, which includes pelvic lymphadenectomy, sentinel lymph node biopsy, abdominal radical trachelectomy, vaginal trachelectomy, or needle conization. Follow-up visits were scheduled at 3 month intervals and included symptom-oriented discussion, gynecological and physical examination, colposcopy, Papanicolaou test, human papillomavirus (HPV) DNA test, and ultrasound examination. All cases with a recurrent disease were thoroughly analyzed, and the results of individual examinations were compared. RESULTS: In total, 43 women (IA2, 8; IB1, 33; IB2, 2) were enrolled. The mean patient age was 31 years; most patients were nulliparous (68.4%, 26/38) with squamous cell cancers (26/38). Abdominal radical trachelectomy was performed in 10 women, simple vaginal trachelectomy was performed in 11 women, and conization was performed in 22 women, according to the tumor characteristics and topography. The median duration of the follow-up reached 37 months. Invasive cancer and high- and low-grade squamous intraepithelial lesions were detected in 8, 1, and 1 patients, respectively. All except 1 event were central, detected within the first year after FSS. Only 2 cases were symptomatic. Colposcopy detected 7 of 10 recurrences; 5 of them were HPV positive, and, in 2 cases, a Papanicolaou test revealed abnormalities. Papanicolaou tests were false positive in 27.7%, especially after trachelectomies. CONCLUSIONS: Most patients in whom cancer recurred after FSS reveal central or pelvic lesions, which can be successfully treated with salvage surgery or radiotherapy. The early detection of recurrence is an essential condition for a favorable oncological outcome. Colposcopy alone and in combination with HPV positivity showed the highest sensitivity for the detection of recurrent diseases, whereas other methods had limited reliability. PMID- 27668394 TI - The Predictive Value of Tumor Size, Volume, and Markers During Radiation Therapy in Patients With Cervical Cancer. AB - OBJECTIVES: We investigated the prognostic significance of changes in primary tumor volume and serum squamous cell carcinoma antigen (SCC-ag) levels during radiation therapy (RT) in patients with cervical cancer. METHODS: We conducted a review of 40 patients treated with RT. All patients received external beam RT and intracavitary brachytherapy. The primary tumor volume and squamous cell carcinoma antigen levels were measured pre-RT and mid-RT. Overall survival (OS) and progression free survival (PFS) were estimated, and possible prognostic factors for survival were analyzed. RESULTS: The correlation coefficient between primary tumor volume reduction rate (pTVRR) and serum squamous cell carcinoma antigen reduction rate in all patients was 0.550 (P < 0.001). In univariate analysis, stage more than II (P <0.001), pre-RT pTV of 55 cm or more (P = 0.05), mid-RT tumor size of 4 cm or more (P = 0.004), and pTVRR of 90% or less (P = 0.031) were significant unfavorable prognostic factors for PFS, whereas stage (P = 0.009) was the only significant prognostic factor for OS. Multivariable analysis revealed that none of these factors were independently associated with PFS or OS. CONCLUSIONS: There was a significant correlation between pTVRR and squamous cell carcinoma antigen reduction rate. Our findings indicate that the tumor parameters such as pre-RT pTV, mid-RT tumor size, and pTVRR are associated with PFS in women with cervical cancer. PMID- 27668395 TI - Extrauterine Spread, Adjuvant Treatment, and Prognosis in Noninvasive Uterine Papillary Serous Carcinoma of the Endometrium: A Retrospective Multicenter Study. AB - OBJECTIVES: The aim of this retrospective multicenter study was to investigate the frequency of extrauterine metastasis and to evaluate the importance of surgical staging and adjuvant treatment among patients with noninvasive uterine papillary serous carcinoma (UPSC) of the endometrium. MATERIALS AND METHODS: A multicenter, retrospective department database review was performed to identify patients with UPSC of the endometrium who underwent surgical staging between 2000 and 2015 at 4 Gynecologic Oncology Centers in Turkey. Demographic, clinicopathological, and survival data were collected. RESULTS: A total of 182 patients with primary UPSC of the endometrium were identified. Of these, 33 (18.1%) had tumors limited to the endometrium with no myometrial invasion. Twenty (60.6%) of these 33 patients had no extrauterine involvement and International Federation of Gynecology and Obstetrics 2009 stage 1A disease was diagnosed after complete staging. The remaining 13 (39.4%) patients had disease beyond the uterine corpus including 5 with omental, 3 with adnexal, 1 with cervical stromal involvement, 1 with disease in the pelvic lymph nodes, and 1 with isolated para aortic lymph node metastasis. Two patients had metastases in more than one location including omentum/adnexa/pelvic-para-aortic lymph nodes and omentum/pelvic-para-aortic lymph nodes, respectively. Of the 20 patients with disease confined to the endometrium, 6 (30%) patients received adjuvant treatment. CONCLUSIONS: Noninvasive UPSC has a high tendency for extrauterine spread and omentum is the most commonly involved location. Therefore, comprehensive surgical staging including omentectomy and pelvic-para-aortic lymph node dissection is mandatory in this group of patients. Risk of extrauterine spread is significantly associated with the presence of lymphovascular space invasion, elevated preoperative CA 125 levels, and positive peritoneal cytology. Adjuvant therapy for women with endometrium-confined disease improves neither progression-free survival nor overall survival. PMID- 27668389 TI - Gene expression elucidates functional impact of polygenic risk for schizophrenia. AB - Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ~20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were <= 1.33, and an independent cohort yielded similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases. PMID- 27668397 TI - Role of Lymphadenectomy for Uterine Sarcoma: A Meta-Analysis. AB - OBJECTIVE: Uterine sarcomas are rare, highly aggressive tumors with an unfavorable prognosis. The role of lymphadenectomy (LAD) remains controversial for this particular tumor type. To examine whether LAD can assist in prognosis or clinical benefits for uterine sarcoma patients, we performed a meta-analysis based on published studies. METHODS: We initially identified published studies by searching the PubMed database up to 30 November 2015. Study quality was evaluated systematically using the Newcastle-Ottawa Scale for assessing the quality of studies for inclusion in meta-analyses. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using Stata software version 12.0. RESULTS: Our search retrieved 14 eligible studies, involving a total of 4867 patients, including 1356 (27.9%) patients who had LAD. The pooled RR for uterine leiomyosarcoma (uLMS) in patients with LAD in 5 trials was 0.90 (95% CI, 0.62 1.31) and for endometrial stromal sarcoma (ESS) in 11 trials was 0.96 (95% CI, 0.69-1.34), suggesting that there was no significant benefit of LAD in improving overall survival (P < 0.05). A random-effects model was chosen to estimate the RRs in view of the significant heterogeneity in the included studies (uLMS: Cochran Q test: P = 0.022, I = 64.9%; ESS: Cochran Q test: P = 0.005, I = 60.1%). No publication bias was detected by the Egger and Begg tests (uLMS: Begg: P = 0.221, Egger: P = 0.148; ESS: Begg: P = 1.000, Egger: P = 0.928). CONCLUSIONS: Based on currently available evidence, the findings of this meta-analysis suggest that LAD bears little prognostic or therapeutic benefit in patients with uterine sarcoma. Systematic LAD may not be recommended in patients with uLMS or ESS unless the patient has obvious extrauterine involvement, clinically suspicious enlarged nodes, or advanced sarcomas. PMID- 27668396 TI - Radical Hysterectomy Plus Concurrent Chemoradiation/Radiation Therapy Is Negatively Associated With Return to Work in Patients With Cervical Cancer. AB - OBJECTIVE: Cervical cancer is one of the most common malignant diseases in working-age women. This study investigated the influence of adverse effects of various treatment modalities on return to work in women with cervical cancer. METHODS: Questionnaires and clinical data from medical records of 97 patients with early stage (stages I and II) cervical cancer were collected and assessed by treatment received. The following treatment groups were analyzed for correlations between time to return to work and various adverse effects: radical hysterectomy (RH) alone, RH group (n = 29); concurrent chemoradiation therapy (CCRT)/radiation therapy (RT) alone, CCRT/RT group (n = 21); and RH + CCRT/RT group (n = 47). The chi test was used to determine the significance of the correlations. RESULTS: The mean age at the time of diagnosis was 43.0 years and the average interval since treatment was 4.5 years. The RH + CCRT/RT group was the most strongly negatively associated with return to work in employed patients who had undergone CCRT/RT group of cervical cancer (P = 0.012). There was a significant association between failure to return to work and lower extremity lymphedema (P = 0.049). A more than 6-month interval between treatment and return to work and reduced personal income occurred in a significantly higher percentage of patients in the RH + CCRT group than in the CCRT/RT group (P = 0.034 and P = 0.034). CONCLUSIONS: Of the treatments assessed, RH + CCRT/RT has the greatest negative effect on return to work in women with cervical cancer. PMID- 27668398 TI - Uterine Clear Cell Carcinoma: Does Adjuvant Chemotherapy Improve Outcomes? AB - OBJECTIVES: Women with uterine clear cell carcinoma (UCCC) are at high risk of relapse. Adjuvant chemotherapy (CT) is often recommended, although its effectiveness remains controversial. Our objective was to evaluate treatment related outcomes of patients with UCCC, particularly those treated with adjuvant CT. METHODS: In this retrospective cohort study, patients diagnosed with UCCC at 2 academic cancer centers from 2000 to 2014 were included. Clinical, surgical, and pathological data were collected. Survival estimates were obtained using the Kaplan-Meier method and compared by log rank test. Multivariable analysis was used to determine the effect of CT and radiation therapy (RT) on overall survival (OS) and progression-free survival (PFS). RESULTS: We included 146 patients with UCCC, with a median follow-up of 27 months (range, 1-160). Ninety-five (65%) patients presented with stage I to II disease and 51 (35%) with stage III to IV disease. Forty-six percent of patients with clinical stage I were upstaged after surgery: 29% were upstaged to stages III and IV. Thirty-one percent of patients with early-stage disease and 70% with advanced-stage received CT. Among recurrences, the majority had distant relapse in both early-stage (61.5%) and advanced-stage (96.3%) diseases. In both patients with early-stage and advanced stage diseases, adjuvant CT did not improve OS or PFS. On multivariate analysis, CT was not a significant factor associated with improved PFS (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.69-2.71; P = 0.37) or OS (HR, 0.58; 95% CI, 0.24-1.38; P = 0.22), whereas RT was associated with improved PFS (HR, 0.51; 95% CI, 0.29-0.90; P = 0.02) and OS (HR, 0.19; 95% CI, 0.09-0.42; P < 0.001). CONCLUSIONS: The high rate of upstaging after surgery highlights the importance of lymph node assessment. The high rate of distant recurrence questions the effectiveness of current CT regimens and warrants the development of novel systemic approaches. The role of adjuvant RT deserves further study. PMID- 27668399 TI - The management of cohesion in written narratives in students with specific language impairment: Differences between childhood and adolescence. AB - The goal of this study was to investigate the management of cohesion by children and adolescents with specific language impairment (SLI) when writing a narrative in a communicative situation. Twelve children with SLI (from 7 to 11 years old) and 12 adolescents with SLI (from 12 to 18 years old) were chronological age matched with 24 typically developing (TD) children and 24 TD adolescents. All participants attended mainstream classes: children in elementary schools and adolescents in middle and high schools. Analyses of cohesion focused on both density and diversity of connectives, punctuation marks and anaphors. Results attested that children with SLI were greatly impaired in their management of written cohesion and used specific forms previously observed in narrative speech such as left dislocations. By contrast, and not expected, the management of written cohesion by adolescents with SLI was close to that of their TD peers. The communicative writing situation we set up, which engaged participants to take into account the addressee, also made possible for adolescents with SLI to manage cohesion in writing. PMID- 27668400 TI - Impact of maladaptive behavior on school function in Down syndrome. AB - BACKGROUND/AIMS: Individuals with Down syndrome (DS) are at an increased risk for certain maladaptive behaviors. This study characterized maladaptive behavior in school-aged children with DS and examined the extent to which maladaptive behaviors are associated with school function. METHODS AND PROCEDURES: Participants were 24 students with DS [mean nonverbal mental age (NVMA)=43.83months; mean chronological age (CA)=77.58months] who completed the Leiter Scales of Performance- Revised (Leiter-R; Roid & Miller, 1997). Their teachers completed the Behavior Assessment Scales for Children Version 2 (Reynolds & Kamphaus, 2004), and the School Function Assessment (Coster et al., 1998), measures of maladaptive and adaptive behavior as observed in the school setting. RESULTS: Findings reveal a maladaptive behavior profile of elevated areas including Aggression, Attention Problems, and Somatization. When examining the association between maladaptive behavior and school function, multivariate regression results indicated a significant association between Aggression and Compliance, and Attention Problems and Task Completion. CONCLUSIONS AND IMPLICATIONS: Results underscore the importance of developing training for educators regarding the potential impact of maladaptive behavior on school function for students with Down syndrome. PMID- 27668401 TI - Benefits of augmentative signs in word learning: Evidence from children who are deaf/hard of hearing and children with specific language impairment. AB - BACKGROUND: Augmentative signs may facilitate word learning in children with vocabulary difficulties, for example, children who are Deaf/Hard of Hearing (DHH) and children with Specific Language Impairment (SLI). Despite the fact that augmentative signs may aid second language learning in populations with a typical language development, empirical evidence in favor of this claim is lacking. AIMS: We aim to investigate whether augmentative signs facilitate word learning for DHH children, children with SLI, and typically developing (TD) children. METHODS AND PROCEDURES: Whereas previous studies taught children new labels for familiar objects, the present study taught new labels for new objects. In our word learning experiment children were presented with pictures of imaginary creatures and pseudo words. Half of the words were accompanied by an augmentative pseudo sign. The children were tested for their receptive word knowledge. OUTCOMES AND RESULTS: The DHH children benefitted significantly from augmentative signs, but the children with SLI and TD age-matched peers did not score significantly different on words from either the sign or no-sign condition. CONCLUSIONS AND IMPLICATIONS: These results suggest that using Sign-Supported speech in classrooms of bimodal bilingual DHH children may support their spoken language development. The difference between earlier research findings and the present results may be caused by a difference in methodology. PMID- 27668403 TI - Going Home, Dying. PMID- 27668404 TI - Repeated blood flow restriction induces muscle fiber hypertrophy. AB - INTRODUCTION: We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. METHODS: Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. RESULTS: CSA was greater in the BFR+ECC group than in the CONT (P < 0.01) and ECC (P < 0.05) groups. CSA was greater in the BFR group than that in the CONT group (P < 0.05). CNCLUSIONS: These results suggest that repeated BFR alone as well as BFR+ECC induces muscle fiber hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. PMID- 27668402 TI - 90K Glycoprotein Promotes Degradation of Mutant beta-Catenin Lacking the ISGylation or Phosphorylation Sites in the N-terminus. AB - beta-Catenin is a major transducer of the Wnt signaling pathway, which is aberrantly expressed in colorectal and other cancers. Previously, we showed that beta-catenin is downregulated by the 90K glycoprotein via ISGylation-dependent degradation. However, the further mechanisms of beta-catenin degradation by 90K mediated ISGylation pathway were not investigated. This study aimed to identify the beta-catenin domain responsible for the action of 90K and to compare the mechanism of 90K on beta-catenin degradation with phosphorylation-dependent ubiquitinational degradation of beta-catenin. The deletion mutants of beta catenin lacking N- or C-terminal domain or mutating the N-terminal lysine or nonlysine residue were employed to delineate the characteristics of beta-catenin degradation by 90K-mediated ISGylation pathway. 90K induced Herc5 and ISG15 expression and reduced beta-catenin levels in HeLa and CSC221 cells. The N terminus of beta-catenin is required for 90K-induced beta-catenin degradation, but the N-terminus of beta-catenin is not essential for interaction with Herc5. However, substituting lysine residues in the N-terminus of beta-catenin with arginine or deleting serine or threonine residue containing domains from the N terminus does not affect 90K-induced beta-catenin degradation, indicating that the N-terminal 86 amino acids of beta-catenin are crucial for 90K-mediated ISGylation/degradation of beta-catenin in which the responsible lysine or nonlysine residues were not identified. Our present results highlight the action of 90K on promoting degradation of mutant beta-catenin lacking the phosphorylation sites in the N-terminus. It provides further insights into the discrete pathway downregulating the stabilized beta-catenin via acquiring mutations at the serine/threonine residues in the N-terminus. PMID- 27668405 TI - The Annals of Medical Assistance in Dying. PMID- 27668406 TI - [Time for Change: What We can Learn from the USA about Primary Care of the Depressed Elderly]. AB - Depression is a common psychiatric disorder in older people. It is often accompanied by comorbid somatic conditions, and affected patients become frequent users of the health care system. Due to its relevance not only for the individual but also for society, reflection on the current health care service and optimization possibilities for the depressed elderly seems important and necessary. Mostly, the general practitioner is not only the first point of contact, but is also responsible for the entire treatment of depression. Due to the limited possibilities of primary care, for several years, there have been collaborative care programs in the USA that provide an optimized networking and collaboration between different health care providers and use specially trained care managers to support the usual primary health care service with short behavioral interventions. In Germany, there are also new approaches and models to improve the health care service for the depressed elderly, but these require further evaluation. PMID- 27668408 TI - Preface. PMID- 27668407 TI - Complex mixtures by NMR and complex NMR for mixtures: experimental and publication challenges. AB - Untargeted strategies have changed the rules of the game in complex mixture analysis, introducing an amazing potential for medical and biological applications that is just starting to be tapped. But with great power come great challenges; although untargeted mixture analysis opens the road for many exciting possibilities, the road is still full of perils. On the one hand, this article highlights some of the difficulties that need to be sorted for mixture analysis by NMR to fulfill its potential, along with insight on how they may be managed. Highlighted key points include the need for 'computer friendly' solutions for sharing data, experimental design and algorithm to facilitate the steady growth of knowledge and modeling ability in the field, and the need for large-scale studies to improve confidence in newly identified biomarkers. On the other hand, the second part of this article presents some breakthroughs in NMR experiments that, when combined, may modify the landscape of mixture analysis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27668409 TI - Advances in an Interdisciplinary Science. PMID- 27668410 TI - Synopsis of Scientific Contributions. PMID- 27668413 TI - Biotechnology and Bioengineering: Volume 113, Number 11, November 2016. PMID- 27668411 TI - Synergy of interleukin 10 and toll-like receptor 9 signalling in B cell proliferation: Implications for lymphoma pathogenesis. AB - A network of autocrine and paracrine signals defines B cell homeostasis and is thought to be involved in transformation processes. Investigating interactions of these microenvironmental factors and their relation to proto-oncogenes as c-Myc (MYC) is fundamental to understand the biology of B cell lymphoma. Therefore, B cells with conditional MYC expression were stimulated with CD40L, insulin-like growth factor 1, alpha-IgM, Interleukin-10 (IL10) and CpG alone or in combination. The impact of forty different interventions on cell proliferation was investigated in MYC deprived cells and calculated by linear regression. Combination of CpG and IL10 led to a strong synergistic activation of cell proliferation (S-phase/doubling of total cell number) comparable to cells with high MYC expression. A synergistic up-regulation of CDK4, CDK6 and CCND3 expression by IL10 and CpG treatment was causal for this proliferative effect as shown by qRT-PCR analysis and inhibition of the CDK4/6 complex by PD0332991. Furthermore, treatment of stimulated MYC deprived cells with MLN120b, ACHP, Pyridone 6 or Ruxolitinib showed that IL10/CpG induced proliferation and CDK4 expression were JAK/STAT3 and IKK/NF-kappaB dependent. This was further supported by STAT3 and p65/RELA knockdown experiments, showing strongest effects on cell proliferation and CDK4 expression after double knockdown. Additionally, chromatin immunoprecipitation revealed a dual binding of STAT3 and p65 to the proximal promotor of CDK4 after IL10/CpG treatment. Therefore, the observed synergism of IL10R and TLR9 signalling was able to induce proliferation in a comparable way as aberrant MYC and might play a role in B cell homeostasis or transformation. PMID- 27668415 TI - Geometry and expression drive yeast biopanning. PMID- 27668414 TI - Low pH bioproduction of succinic acid in yeast. PMID- 27668412 TI - Identification of rare variants in KCTD13 at the schizophrenia risk locus 16p11.2. AB - Duplications in 16p11.2 are a risk factor for schizophrenia (SCZ). Using genetically modified zebrafish, Golzio and colleagues identified KCTD13 within 16p11.2 as a major driver of the neuropsychiatric phenotype observed in humans. The aims of the present study were to explore the role of KCTD13 in the development of SCZ and to provide a more complete picture of the allelic architecture at this risk locus. The exons of KCTD13 were sequenced in 576 patients. The mutations c.6G>T and c.598G>A were identified in one patient each. Both mutations were predicted to be functionally relevant and were absent from the 1000 Genomes Project data and the Exome Variant Server. The mutation c.6G>T was predicted to abolish a potential transcription factor-binding site for specifity protein 1. Altered specifity protein 1 expression has been reported in SCZ patients compared with controls. Further studies in large cohorts are warranted to determine the relevance of the two identified mutations. PMID- 27668417 TI - Genome-scale RNA interference screen. PMID- 27668416 TI - Engineering E. coli to improve the secretion capacity of SRP pathway. PMID- 27668419 TI - Chronic Disease Prevention: Tobacco Avoidance, Physical Activity, and Nutrition for a Healthy Start. PMID- 27668420 TI - Genetic disruption of the KLF1 gene to overexpress the gamma-globin gene using the CRISPR/Cas9 system. AB - BACKGROUND: beta-thalassemia comprises a major group of human genetic disorders involving a decrease in or an end to the normal synthesis of the beta-globin chains of hemoglobin. KLF1 is a key regulatory molecule involved in the gamma- to beta-globin gene switching process directly inducing the expression of the beta globin gene and indirectly repressing gamma-globin. The present study aimed to investigate the ability of an engineered CRISPR/Cas9 system with respect to disrupting the KLF1 gene to inhibit the gamma- to beta-hemoglobin switching process in K562 cells. METHODS: We targeted three sites on the KLF1 gene, two of which are upstream of codon 288 in exon 2 and the other site being in exon 3. RESULTS: The average indel percentage in the cells transfected with CRISPR a, b and c was approximately 24%. Relative quantification was performed for the assessment of gamma-globin expression. The levels of gamma-globin mRNA on day 5 of differentiation were 8.1-, 7.7- and 1.8-fold in the cells treated with CRISPR/Cas9 a, b and c, respectively,compared to untreated cells. The measurement of HbF expression levels confirmed the same results. CONCLUSIONS: The findings obtained in the present study support the induction of an indel mutation in the KLF1 gene leading to a null allele. As a result, the effect of KLF1 on the expression of BCL11A is decreased and its inhibitory effect on gamma-globin gene expression is removed. Application of CRISPR technology to induce an indel in the KLF1 gene in adult erythroid progenitors may provide a method for activating fetal hemoglobin expression in individuals with beta-thalassemia or sickle cell disease. PMID- 27668421 TI - Changing dynamics: Time-varying autoregressive models using generalized additive modeling. AB - In psychology, the use of intensive longitudinal data has steeply increased during the past decade. As a result, studying temporal dependencies in such data with autoregressive modeling is becoming common practice. However, standard autoregressive models are often suboptimal as they assume that parameters are time-invariant. This is problematic if changing dynamics (e.g., changes in the temporal dependency of a process) govern the time series. Often a change in the process, such as emotional well-being during therapy, is the very reason why it is interesting and important to study psychological dynamics. As a result, there is a need for an easily applicable method for studying such nonstationary processes that result from changing dynamics. In this article we present such a tool: the semiparametric TV-AR model. We show with a simulation study and an empirical application that the TV-AR model can approximate nonstationary processes well if there are at least 100 time points available and no unknown abrupt changes in the data. Notably, no prior knowledge of the processes that drive change in the dynamic structure is necessary. We conclude that the TV-AR model has significant potential for studying changing dynamics in psychology. (PsycINFO Database Record PMID- 27668422 TI - Cytogenetic Biomonitoring in Buccal Mucosa Cells of Young Smokers. PMID- 27668423 TI - Molecular Cytogenetic Characterization of New Wheat-Rye 1R(1B) Substitution and Translocation Lines from a Chinese Secale cereal L. Aigan with Resistance to Stripe Rust. AB - Secale cereale L. has been used worldwide as a source of genes for agronomic and resistance improvement. In this study, a stable wheat-rye substitution line and 3 primary 1RS.1BL translocation lines were selected from the progeny of the crossing of the Chinese local rye Aigan variety and wheat cultivar Mianyang11. The substitution and translocation lines were identified by molecular cytogenetic analysis. PCR results, fluorescence in situ hybridization and acid polyacrylamide gel electrophoresis indicated that there were a pair of 1R chromosomes in the substitution line which have been named RS1200-3, and a pair of 1RS.1BL translocation chromosomes in the other 3 translocation lines, which have been named RT1163-4, RT1217-1, and RT1249. When inoculated with stripe rust isolates, these 4 lines expressed high resistance to several Puccinia striiformis f. sp Tritici pathotypes that are virulent on Yr9. Moreover, the different response pattern of resistance among them suggested that the diversity of resistance genes for wheat stripe rust exists in the rye. These 4 lines also showed better agronomic performances than their wheat parent. The GS indices also showed the genetic diversity of the 1RS which derived from same rye variety. The present study indicates that rye cultivars may carry untapped variations that could potentially be used for wheat improvement. PMID- 27668425 TI - Explicit spatial compatibility is not critical to the object handle effect. AB - In object perception studies, a response advantage arises when the handle of an object is congruent with the responding hand. This handle effect is thought to reflect increased motor activation of the hand most suited to grasp the object, consistent with affordance theories of object representation. An alternative explanation has been proposed, however, which suggests that the handle effect is related to a simple spatial compatibility effect (the Simon effect). In 3 experiments, we determined whether the handle effect would emerge in the absence of explicit spatial compatibility between handle and response. Stimulus and response location was varied vertically and participants made horizontally orthogonal, bimanual responses to objects' kitchen/garage category, color (as in a traditional Simon effect) or upright/inverted orientation. Categorization and inversion tasks, which relied on object knowledge, elicited a handle effect and a vertical Simon effect regarding stimulus and response locations. When participants judged object color, as per standard Simon effect paradigms, the handle effect disappeared but the Simon effect strengthened. These data demonstrate a dissociation between affordance and spatial compatibility effects and prove that affordance plays an important role in the handle effect. Models that incorporate both affordance and spatial compatibility mechanisms are discussed. (PsycINFO Database Record PMID- 27668424 TI - Hierarchical nesting of affordances in a tool use task. AB - In studying the perception of affordances, researchers have typically identified a single affordance and designed experiments to evaluate the perception of that affordance. Yet in daily life, multiple affordances always exist. One consequence of this is that there may be higher order, means-ends relations between different affordances. In 4 experiments, we created situations in which lower order, subordinate affordances could affect the realization of higher order, superordinate affordances, and we asked whether participants were sensitive to these hierarchical, nested relations. Participants wielded tools that varied in length, mass, and mass distribution. In Experiments 1 and 2, we asked them to evaluate these tools in terms of their suitability for executing specific interactions with target objects (striking vs. poking) that were positioned at different distances. In Experiments 3 and 4, we asked participants to select rods and masses and then to assemble them into tools that could be used to execute specific interactions with target objects at different distances. The results were compatible with the hypothesis that participants were simultaneously sensitive to affordances for tool assembly and affordances for tool use. We argue that the nesting of affordances is characteristic of many situations in daily life and that, consequently, sensitivity to hierarchical, means-ends relations among affordances may be an essential characteristic of perceptually guided action. (PsycINFO Database Record PMID- 27668426 TI - Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs. AB - The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild type. Importantly, increased sensitivity of unc-25 and unc-49 mutants to electric shock is rescued by treatment with antiepileptic drugs, such as retigabine. Additionally, we show that pentylenetetrazol (PTZ), a GABAA receptor antagonist and proconvulsant in mammalian and C. elegans seizure models, increases susceptibility of worms to electric shock. PMID- 27668427 TI - Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer. AB - BACKGROUND: Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients. METHODS: We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer. RESULTS: The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026). CONCLUSIONS: These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend to have a longer overall survival time. Thus, eIF4G1 may contribute to the occurrence and metastasis of ovarian cancer and can serve as a potential therapeutic target for the treatment of ovarian cancer. PMID- 27668428 TI - N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors. AB - The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32-35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR. PMID- 27668430 TI - Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy. AB - BACKGROUND: A non-invasive diagnostic marker of membranous nephropathy (MN) is desirable. The urinary level of podocalyxin (PCX) is higher in various glomerular diseases, including MN. The aim of this study was to construct a diagnostic model of MN with the combination of urinary PCX and clinical parameters. METHODS: We performed this cross-sectional study to construct the diagnostic models for MN by using data and samples from the multicenter kidney biopsy registry of Nagoya University and its affiliated hospitals. Urinary (u-) PCX was measured by sandwich ELISA. We constructed 3 types of diagnostic models in 105 training samples: u-PCX univariate model, the combined model of clinical parameters other than u-PCX (clinical model), and the combined model of both u-PCX and clinical parameters (combined model). We assessed the clinical usefulness of the diagnostic models through the comparison of c-statistics and decision curve analysis (DCA) in 209 validation samples. RESULTS: The clinical model consisted of age, glomerular filtration rate, and diabetes mellitus. In the training cohort, the c-statistics were 0.868 [95% CI, 0.799-0.937] in the combined model. In the validation cohort, sensitivity was 80.5% and specificity was 73.5% on the cut-off value. The net benefit of the combined model was better between threshold probabilities of 40-80% in DCA. CONCLUSIONS: In this study, we demonstrated the utility of u-PCX as a diagnostic marker for MN and the clinical usefulness of the diagnostic models, through the combination of u-PCX and clinical parameters including age, glomerular filtration rate, and diabetes mellitus. PMID- 27668429 TI - Movement Protein of Cucumber Mosaic Virus Associates with Apoplastic Ascorbate Oxidase. AB - Plant viral movement proteins facilitate virion movement mainly through interaction with a number of factors from the host. We report the association of a cell wall localized ascorbate oxidase (CsAO4) from Cucumis sativus with the movement protein (MP) of Cucumber mosaic virus (CMV). This was identified first in a yeast two-hybrid screen and validated by in vivo pull down and bimolecular fluorescence complementation (BiFC) assays. The BiFC assay showed localization of the bimolecular complexes of these proteins around the cell wall periphery as punctate spots. The expression of CsAO4 was induced during the initial infection period (up to 72 h) in CMV infected Nicotiana benthamiana plants. To functionally validate its role in viral spread, we analyzed the virus accumulation in CsAO4 overexpressing Arabidopsis thaliana and transiently silenced N. benthamiana plants (through a Tobacco rattle virus vector). Overexpression had no evident effect on virus accumulation in upper non-inoculated leaves of transgenic lines in comparison to WT plants at 7 days post inoculation (dpi). However, knockdown resulted in reduced CMV accumulation in systemic (non-inoculated) leaves of NbDeltaAO-pTRV2 silenced plants as compared to TRV inoculated control plants at 5 dpi (up to 1.3 fold difference). In addition, functional validation supported the importance of AO in plant development. These findings suggest that AO and viral MP interaction helps in early viral movement; however, it had no major effect on viral accumulation after 7 dpi. This study suggests that initial induction of expression of AO on virus infection and its association with viral MP helps both towards targeting of the MP to the apoplast and disrupting formation of functional AO dimers for spread of virus to nearby cells, reducing the redox defense of the plant during initial stages of infection. PMID- 27668432 TI - Clinical Characteristics of Benign Pediatric Cranial Vault Tumors: Surgical Considerations Based on 100 Cases. AB - BACKGROUND/AIMS: Tumors of the cranial vault occur at every age of childhood. Although they are mostly benign lesions, their symptomatology is variable and requires extended diagnostics. The choice of therapeutic strategy strongly depends on histopathological diagnosis, and therefore surgical excision is the elective treatment in such cases. Despite several published papers, the literature still lacks reliable clinical characteristics regarding this heterogeneous group of lesions in pediatric patients. METHODS: We present a series of 100 children (55 male, 45 female) with scalp and cranial vault masses (average age: 3.6 years; range: 1 month to 17 years). Eighty-three (83%) patients underwent surgical excision. Demographic data, clinical presentation, diagnostic studies, choice of therapy, and the results of treatment were evaluated. RESULTS: All removed tumors were benign pathologies: pilar cysts (30%), epidermoid/dermoid cysts (21%), vascular malformations (11%), inflammatory tumors (5%), and dysraphic remnants (2%). However, underlying bone destruction was observed in 61% of cases. Cranial extension occurred in 34%. Recurrence was noted in 1 case. CONCLUSIONS: Cranial vault tumors are characterized by constant growth and may penetrate the cranial cavity. Delayed surgery increases the risk of intracranial complications. Surgical problems include inappropriate planning, higher risk of intraoperative bleeding, and the need for subsequent cranioplasty. PMID- 27668431 TI - Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling. AB - TFE-fusion renal cell carcinomas (TFE-fusion RCCs) are caused by chromosomal translocations that lead to overexpression of the TFEB and TFE3 genes (Kauffman et al., 2014). The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system (Kauffman et al., 2014). Here, we show that kidney-specific TFEB overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases. These features closely recapitulate those observed in both TFEB- and TFE3-mediated human kidney tumors. Analysis of kidney samples revealed transcriptional induction and enhanced signaling of the WNT beta-catenin pathway. WNT signaling inhibitors normalized the proliferation rate of primary kidney cells and significantly rescued the disease phenotype in vivo. These data shed new light on the mechanisms underlying TFE-fusion RCCs and suggest a possible therapeutic strategy based on the inhibition of the WNT pathway. PMID- 27668433 TI - Quantifying the Twitter Influence of Third Party Commercial Entities versus Healthcare Providers in Thirteen Medical Conferences from 2011 - 2013. AB - INTRODUCTION: Twitter channels are increasingly popular at medical conferences. Many groups, including healthcare providers and third party entities (e.g., pharmaceutical or medical device companies) use these channels to communicate with one another. These channels are unregulated and can allow third party commercial entities to exert an equal or greater amount of Twitter influence than healthcare providers. Third parties can use this influence to promote their products or services instead of sharing unbiased, evidence-based information. In this investigation we quantified the Twitter influence that third party commercial entities had in 13 major medical conferences. METHODS: We analyzed tweets contained in the official Twitter hashtags of thirteen medical conferences from 2011 to 2013. We placed tweet authors into one of four categories based on their account profile: healthcare provider, third party commercial entity, none of the above and unknown. We measured Twitter activity by the number of tweet authors per category and the tweet-to-author ratio by category. We measured Twitter influence by the PageRank of tweet authors by category. RESULTS: We analyzed 51159 tweets authored by 8778 Twitter account holders in 13 conferences that were sponsored by 5 medical societies. A quarter of all authors identified themselves as healthcare providers, while only 18% could be identified as third party commercial entities. Healthcare providers had a greater tweet-to-author ratio than their third party commercial entity counterparts (8.98 versus 6.93 tweets). Despite having less authors and composing less tweets, third party commercial entities had a statistically similar PageRank as healthcare providers (0.761 versus 0.797). CONCLUSION: The Twitter influence of third party commercial entities (PageRank) is similar to that of healthcare providers. This finding is interesting because the number of tweets and third party commercial entity authors required to achieve this PageRank is far fewer than that needed by healthcare providers. Without safety mechanisms in place, the Twitter channels of medical conferences can devolve into a venue for the spread of biased information rather than evidence-based medical knowledge that is expected at live conferences. Continuing to measure the Twitter influence that third parties exert can help conference organizers develop reasonable guidelines for Twitter channel activity. PMID- 27668436 TI - Health Care in a Digital Age. PMID- 27668434 TI - The Challenge of Stability in High-Throughput Gene Expression Analysis: Comprehensive Selection and Evaluation of Reference Genes for BALB/c Mice Spleen Samples in the Leishmania infantum Infection Model. AB - The interaction of Leishmania with BALB/c mice induces dramatic changes in transcriptome patterns in the parasite, but also in the target organs (spleen, liver...) due to its response against infection. Real-time quantitative PCR (qPCR) is an interesting approach to analyze these changes and understand the immunological pathways that lead to protection or progression of disease. However, qPCR results need to be normalized against one or more reference genes (RG) to correct for non-specific experimental variation. The development of technical platforms for high-throughput qPCR analysis, and powerful software for analysis of qPCR data, have acknowledged the problem that some reference genes widely used due to their known or suspected "housekeeping" roles, should be avoided due to high expression variability across different tissues or experimental conditions. In this paper we evaluated the stability of 112 genes using three different algorithms: geNorm, NormFinder and RefFinder in spleen samples from BALB/c mice under different experimental conditions (control and Leishmania infantum-infected mice). Despite minor discrepancies in the stability ranking shown by the three methods, most genes show very similar performance as RG (either good or poor) across this massive data set. Our results show that some of the genes traditionally used as RG in this model (i.e. B2m, Polr2a and Tbp) are clearly outperformed by others. In particular, the combination of Il2rg + Itgb2 was identified among the best scoring candidate RG for every group of mice and every algorithm used in this experimental model. Finally, we have demonstrated that using "traditional" vs rationally-selected RG for normalization of gene expression data may lead to loss of statistical significance of gene expression changes when using large-scale platforms, and therefore misinterpretation of results. Taken together, our results highlight the need for a comprehensive, high-throughput search for the most stable reference genes in each particular experimental model. PMID- 27668435 TI - Spatial Dynamics and High Risk Transmission Pathways of Poliovirus in Nigeria 2001-2013. AB - The polio eradication programme in Nigeria has been successful in reducing incidence to just six confirmed cases in 2014 and zero to date in 2015, but prediction and management of future outbreaks remains a concern. A Poisson mixed effects model was used to describe poliovirus spread between January 2001 and November 2013, incorporating the strength of connectivity between districts (local government areas, LGAs) as estimated by three models of human mobility: simple distance, gravity and radiation models. Potential explanatory variables associated with the case numbers in each LGA were investigated and the model fit was tested by simulation. Spatial connectivity, the number of non-immune children under five years old, and season were associated with the incidence of poliomyelitis in an LGA (all P < 0.001). The best-fitting spatial model was the radiation model, outperforming the simple distance and gravity models (likelihood ratio test P < 0.05), under which the number of people estimated to move from an infected LGA to an uninfected LGA was strongly associated with the incidence of poliomyelitis in that LGA. We inferred transmission networks between LGAs based on this model and found these to be highly local, largely restricted to neighbouring LGAs (e.g. 67.7% of secondary spread from Kano was expected to occur within 10 km). The remaining secondary spread occurred along routes of high population movement. Poliovirus transmission in Nigeria is predominantly localised, occurring between spatially contiguous areas. Outbreak response should be guided by knowledge of high-probability pathways to ensure vulnerable children are protected. PMID- 27668439 TI - Navigating Medicare Part D Websites: Are the Part D Plans in Compliance? AB - Today, more than one half of older adults use the internet to obtain health related information, and there is growing interest from governmental agencies in providing information online. The Centers for Medicare & Medicaid Services (CMS) provides guidance to Part D prescription drug plan sponsors about information to include on their websites. The current article examines compliance with the 2014 CMS guidance for Medication Therapy Management (MTM) program information on Part D plan sponsors' websites. There were 59.5% of plan sponsors that had a dedicated MTM program webpage, accessible within two clicks from the plan sponsor's home page and provided basic information, eligibility for MTM services, and access to a blank copy of a personalized medication list document. Although improvements in the provision of information about plan sponsors' MTM programs can be made, future work should evaluate the usability and effectiveness of the online MTM program information provided to Medicare beneficiaries. [Journal of Gerontological Nursing, 42(10), 9-14.]. PMID- 27668440 TI - Multidisciplinary Comprehensive Care for Early Recommencement of Oral Intake in Older Adults With Severe Pneumonia. AB - HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.3 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Multidisciplinary Comprehensive Care for Early Recommencement of Oral Intake in Older Adults With Severe Pneumonia" found on pages 21-29, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until September 30, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe the effect of multidisciplinary comprehensive care (MDCC) on oral intake in older adults with severe pneumonia at the time of discharge. 2. Explore the impact of MDCC on the length of stay for hospitalized older adults with severe pneumonia. DISCLOSURE STATEMENT Neither the planners nor the authors have any conflicts of interest to disclose. The current study was designed to assess the effect of multidisciplinary comprehensive care (MDCC) on (a) oral intake at discharge and (b) hospital stay duration in older adult patients with severe pneumonia. Participants were divided into two groups: receiving and not receiving MDCC. MDCC comprises regular assessment of swallowing ability, aspiration risk management, improvement of oral hygiene, serving of nutritious texture-modified foods, and encouragement of early mobilization. The MDCC group (164 women, 206 men; mean age = 82.7, SD = 8.4 years) had severe pneumonia as well as high proportions of poor premorbid physical function and consciousness disturbance compared to the non MDCC group (45 women, 56 men; mean age = 81.1, SD = 8.6 years). Nevertheless, MDCC was an independent determinant of hospital stay duration and oral intake (Functional Oral Intake Scale score >=4) at discharge with Cox regression analysis (hazard ratio = 1.42, 95% confidence interval [1.09, 1.85]). MDCC may promote early oral intake and hospital discharge in older adults with severe pneumonia. [Journal of Gerontological Nursing, 42(10), 21-29.]. PMID- 27668442 TI - Lateral Diffusion and Molecular Interaction in a Bilayer Membrane Consisting of Partially Fluorinated Phospholipids. AB - Fluorinated lipids and surfactants are attractive biomimetic materials for the extraction and reorganization of membrane proteins because of the biological inertness of fluorocarbons. We investigated the fundamental physical properties of a partially fluorinated phospholipid (F4-DMPC), such as phase transition, area thermal expansion, and lateral lipid diffusion, to evaluate the intermolecular interaction of F4-DMPC in the hydrophobic region quantitatively on the basis of free-volume theory. Fluorescence microscope observation of the supported lipid bilayer (SLB) of F4-DMPC showed that the phase transition between the liquid crystalline and gel phases occurred at 5 degrees C and that the area thermal expansion coefficient was independent of the temperature near the phase transition temperature. We performed a single particle tracking of the F4-DMPC SLB on a SiO2/Si substrate, to measure the diffusion coefficient and its temperature dependence. The apparent activation energy (E'a) of lateral lipid diffusion, which is an indicator of intermolecular interaction, was 39.1 kJ/mol for F4-DMPC, and 48.2 kJ/mol for a nonfluorinated 1,2-dioleoyl-sn-glycero-3 phosphocholine as a control. The difference of 9 kJ/mol in E'a was significant compared with the difference due to the acyl chain species among nonfluorinated phosphatidylcholine and also that caused by the addition of cholesterol and alcohol in the bilayer membranes. We quantitatively evaluated the attenuation of intermolecular interaction, which results from the competition between the dipole induced packing effect and steric effect at the fluorocarbon segment in F4-DMPC. PMID- 27668443 TI - Effects of Differentiation and Antisenescence from BMSCs to Hepatocy-Like Cells of the PAAm-IGF-1/TNF-alpha Biomaterial. AB - Aiming at the cells' differentiation phenomenon and senescence problem in liver tissue engineering, this work is designed to synthesize three different chargeable polymers (polypropylene acid (PAAc), polyethylene glycol (PEG), and polypropylene amine (PAAm)) coimmobilized by the insulin-like growth factor 1 (IGF-1) and tumor necrosis factor-alpha (TNF-alpha). We explore the hepatocyte differentiation effect and the antisenecence effect of PSt-PAAm-IGF-1/TNF-alpha biomaterial which was selected from the three different chargeable polymers in bone marrow mesenchymal stem cells (BMSCs). Our work will establish a model for studying the biochemical molecular regulation mechanism and signal transduction pathway of cell senescence in liver tissue engineering, which provide a molecular basis for developing biomaterials for liver tissue engineering. PMID- 27668444 TI - Bisboronic Acids for Selective, Physiologically Relevant Direct Glucose Sensing with Surface-Enhanced Raman Spectroscopy. AB - This paper demonstrates the direct sensing of glucose at physiologically relevant concentrations with surface-enhanced Raman spectroscopy (SERS) on gold film-over nanosphere (AuFON) substrates functionalized with bisboronic acid receptors. The combination of selectivity in the bisboronic acid receptor and spectral resolution in the SERS data allow the sensors to resolve glucose in high backgrounds of fructose and, in combination with multivariate statistical analysis, detect glucose accurately in the 1-10 mM range. Computational modeling supports assignments of the normal modes and vibrational frequencies for the monoboronic acid base of our bisboronic acids, glucose and fructose. These results are promising for the use of bisboronic acids as receptors in SERS-based in vivo glucose monitoring sensors. PMID- 27668445 TI - Mechanistic Studies on RNA Strand Scission from a C2'-Radical. AB - The C2'-carbon-hydrogen bond in ribonucleotides is significantly weaker than other carbohydrate carbon-hydrogen bonds in RNA or DNA. Independent generation of the C2'-uridine radical (1) in RNA oligonucleotides via Norrish type I photocleavage of a ketone-substituted nucleotide yields direct strand breaks via cleavage of the beta-phosphate. The reactivity of 1 in different sequences and under a variety of conditions suggests that the rate constant for strand scission is significantly greater than 106 s-1 at pH 7.2. The initially formed C2'-radical (1) is not trapped under a variety of conditions, consistent with computational studies ( Chem.-Eur. J. 2009 , 15 , 2394 ) that suggest that the barrier to strand scission is very low and that synchronous proton transfer from the 2' hydroxyl to the departing phosphate group facilitates cleavage. The C2'-radical could be a significant contributor to RNA strand scission by the hydroxyl radical, particularly under anaerobic conditions where 1 can be produced from nucleobase radicals. PMID- 27668446 TI - Synthesis of Trifluoromethyl-allenes by Gold-Catalyzed Rearrangement of Propargyl Benzyl Ethers. AB - A new method for the synthesis of trifluoromethyl-allenes from easily accessible alpha-trifluoromethyl-propargyl benzyl ether derivatives following a gold catalyzed intramolecular hydride transfer has been developed. Various di- and trisubstituted trifluoromethyl-allenes were obtained in good to excellent yields. PMID- 27668448 TI - Chlorine Incorporation in the CH3NH3PbI3 Perovskite: Small Concentration, Big Effect. AB - The role of chlorine doping in CH3NH3PbI3 represents an important open issue in the use of hybrid perovskites for photovoltaic applications. In particular, even if a positive role of chlorine doping on perovskite film formation and on material morphology has been demonstrated, an inherent positive effect on the electronic and photovoltaic properties cannot be excluded. Here we carried out periodic density functional theory and Car-Parrinello molecular dynamics simulations, going down to ~1% doping, to investigate the effect of chlorine on CH3NH3PbI3. We found that such a small doping has important effects on the dynamics of the crystalline structure, both with respect to the inorganic framework and with respect to the cation libration motion. Together, we observe a dynamic spatial localization of the valence and conduction states in separated spatial material regions, which takes place in the 10-1 ps time scale and which could be the key to ease of exciton dissociation and, likely, to small charge recombination in hybrid perovskites. Moreover, such localization is enhanced by chlorine doping, demonstrating an inherent positive role of chlorine doping on the electronic properties of this class of materials. PMID- 27668447 TI - Molecular Plasmon-Phonon Coupling. AB - Charged polycyclic aromatic hydrocarbons (PAHs), ultrasmall analogs of hydrogen terminated graphene consisting of only a few fused aromatic carbon rings, have been shown to possess molecular plasmon resonances in the visible region of the spectrum. Unlike larger nanostructures, the PAH absorption spectra reveal rich, highly structured spectral features due to the coupling of the molecular plasmons with the vibrations of the molecule. Here, we examine this molecular plasmon phonon interaction using a quantum mechanical approach based on the Franck-Condon approximation. We show that an independent boson model can be used to describe the complex features of the PAH absorption spectra, yielding an analytical and semiquantitative description of their spectral features. This investigation provides an initial insight into the coupling of fundamental excitations-plasmons and phonons-in molecules. PMID- 27668449 TI - Facet-Dependent Photocatalytic N2 Fixation of Bismuth-Rich Bi5O7I Nanosheets. AB - Bismuth-rich bismuth oxyhalides (Bi-O-X; X = Cl, Br, I) display high photocatalytic reduction activity due to the promoting conduction band potential. In this work, two Bi5O7I nanosheets with different dominant facets were synthesized using either molecular precursor hydrolysis or calcination. Crystal structure characterizations, included X-ray diffraction patterns (XRD), field emission electron microscopy and fast Fourier transformation (FFT) images, showed that hydrolysis and calcination resulted in the dominant exposure of {100} and {001} facets, respectively. Photocatalytic data revealed that Bi5O7I-001 had a higher activity than Bi5O7I-100 for N2 fixation and dye degradation. Photoelectrochemical data revealed that Bi5O7I-001 had higher photoinduced carrier separation efficiency than Bi5O7I-100. The band structure analysis also used to explain the underlying photocatalytic mechanism based on the different conduction band position. This work presents the first report about the facet dependent photocatalytic performance of bismuth-rich Bi-O-X photocatalysts. PMID- 27668450 TI - Kinetics and Products from Heterogeneous Oxidation of Squalene with Ozone. AB - Motivated by the importance of the heterogeneous chemistry of squalene contained within skin oil to indoor air chemistry, the surface reaction of squalene with gas-phase ozone has been investigated. Using direct analysis in real time mass spectrometry (DART-MS) to monitor squalene, the reactive uptake coefficients were determined to be (4.3 +/- 2.2) * 10-4 and (4.0 +/- 2.2) * 10-4 for ozone mixing ratios (MRO3) of 50 and 25 ppb, respectively, on squalene films deposited on glass surfaces. At an MRO3 of 25 ppb, the lifetime for oxidation was the same as that in an indoor office with an MRO3 between 22 and 32 ppb, suggesting that O3 was the dominant oxidant in this indoor setting. While the heterogeneous kinetics of squalene and O3 were independent of relative humidity (RH), the RH significantly affected the reaction products. Under dry conditions (<5% RH), in addition to several products between m/z 300 and 350, the major condensed-phase end products were levulinic acid (LLA) and succinic acid (SCA). Under humid conditions (50% RH), the major end products were 4-oxopentanal, 4-oxobutanoic acid, and LLA. The molar yields of LLA and SCA were quantified as 230 +/- 43% and 110 +/- 31%, respectively, under dry conditions and 91 +/- 15% and <5%, respectively, at 50% RH. Moreover, high-molecular weight (molecular weight of >450 Da) products were observed under dry conditions with indications that LLA was involved in their formation. The mechanism of squalene oxidation is discussed in light of these observations, with indications of an important role played by Criegee intermediates. PMID- 27668451 TI - Her Glistening Eyes. PMID- 27668452 TI - Symptoms associated with teething and response to three treatments, including homeopathic medicine: a multicenter prospective observational study among 190 French pediatricians. AB - BACKGROUND: Primary tooth eruption in infants is associated with a range of local and systemic symptoms although this remains a subject of much debate. In addition, data is limited for the role of physicians in managing infant teething, and for the benefit of homeopathic treatments. METHODS: We conducted an observational, multicenter, prospective survey evaluating teething symptoms, and symptom course following routine medical management by French pediatricians in 597 infants aged from 3 to 24 months. We also examined response to treatment with routinely prescribed teething medications; the homeopathic agent, Camilia(r) and topically applied gingival agents (Delabarre(r) or Dolodent(r)). RESULTS: Most infants (96.6%) had buccogingival symptoms and 93.3% had at least one general symptom. Fever (>=38 degrees C) was reported in 15.2% of infants. For teething, 212 infants were prescribed Camilia(r), 172 a gingival solution (Delabarre(r) or Dolodent(r)) and 213 received Camilia(r) along with a gingival agent. Infants prescribed both a homeopathic and a gingival treatment had a significantly higher number of symptoms at presentation compared with those prescribed a single agent. There were no significant differences in symptom course across these three treatment groups. Systemic analgesics/antipyretics were prescribed in 68.8% of cases. Parent satisfaction with medical management and prescribed treatments was high. CONCLUSION: Teething is frequently associated with transient local and systemic upset in infants and is a significant concern to parents. Camilia(r) provides a similar benefit to topical therapy, and is frequently used by pediatricians in France. PMID- 27668453 TI - Usefulness of fecal calprotectin determination in pediatric intestinal diseases. AB - Calprotectin is a heterodimeric protein which belongs to the calcium-binding protein S100 family. Calprotectin is released by leukocytes at the site of inflammation and it can be detected in the feces where it remains stable for about a week. Hence, increased fecal calprotectin (FC) levels are found in several inflammatory conditions, mainly the inflammatory bowel diseases (IBD). In the setting of pediatric gastroenterology, the importance of FC has increased over time. This review aims to summarize the most recent findings concerning the role of FC in the algorithm of different inflammatory and non-inflammatory conditions among pediatric patients. Increasing evidences support the use of this biomarker for diagnosis, follow-up and evaluation of response to therapy of several pediatric gastrointestinal diseases, ranging from IBD to lymphocytic/ eosinophilic/ and nonspecific colitis and necrotizing enterocolitis. More efforts should be done to clarify the optimal cut-off of FC levels in patients younger than 5 years. PMID- 27668454 TI - A Content Analysis of Newspaper Coverage of the Seasonal Flu Vaccine in Ontario, Canada, October 2001 to March 2011. AB - Seasonal flu vaccine uptake has fallen dramatically over the past decade in Ontario, Canada, despite promotional efforts by public health officials. Media can be particularly influential in shaping the public response to seasonal flu vaccine campaigns. We therefore sought to identify the nature of the relationship between risk messages about getting the seasonal flu vaccine in newspaper coverage and the uptake of the vaccine by Ontarians between 2001 and 2010. A content analysis was conducted to quantify risk messages in newspaper content for each year of analysis. The quantification allowed us to test the correlation between the frequency of risk messages and vaccination rates. During the time period 2001-2010, vaccination rates were positively and significantly related to the frequency of risk messages in newspaper coverage (r = .691, p < .05). The most commonly identified risk messages related to the flu vaccine being ineffective, the flu vaccine being poorly understood by science, and the flu vaccine causing harm. Newspaper coverage plays an important role in shaping public response to seasonal flu vaccine campaigns. Public health officials should work alongside media to ensure that the public are exposed to information necessary for making informed decisions regarding vaccination. PMID- 27668455 TI - The host-pathogen interaction in Campylobacter jejuni infection of chickens: An understudied aspect that is crucial for effective control. PMID- 27668456 TI - Purification and characterization of a novel fibrinolytic enzyme from Whitmania pigra Whitman. AB - A fibrinolytic enzyme was purified from the dry body of Whitmania pigra Whitman. The fibrinolytic enzyme was purified to homogeneity with a yield of 0.003% and a purification of 630.7 fold. The molecular weight of the enzyme was estimated to be 26.7 kDa by reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme was tested by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and it showed that the enzyme was a novel fibrinolytic enzyme. The optimal pH and temperature of the enzyme were 8.5 and 55 degrees C, respectively. Enzyme activity was enhanced by Na+, Mg2+, and K+. On the contrary, the proteolytic activity was significantly inhibited by Mn2+, Fe2+, Fe3+, ethylenediaminetetraacetic acid (EDTA), and ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA). Fibrinolytic and fibrinogenolytic assays showed that the enzyme preferentially hydrolyzed fibrinogen Aalpha-chains, followed by Bbeta- and gamma-chains. The alpha-, beta-, and gamma-gamma-chains of fibrin were also degraded by the enzyme. PMID- 27668457 TI - Sleep quality, chronotype and social jetlag differentially associate with symptoms of attention deficit hyperactivity disorder in adults. AB - Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder which has been associated with sleep and circadian rhythm disturbances. Numerous studies have linked evening circadian typology with traits and behaviours associated with the disorder, although a precise reason for this relationship has not been clarified. The current study examines ADHD symptoms, impulsivity, cognitive failures, sleep quality and chronotype in a cohort of healthy young adults (N = 396). Results show significant, small magnitude associations between mid-point of sleep on free days, social jetlag (SJL) and ADHD symptoms and impulsivity, although not with cognitive failures. Similarly, sleep quality is also associated with ADHD symptoms and impulsivity. Group-wise approaches show that higher SJL is associated with significantly more ADHD symptoms and impulsivity, and later mid-sleep on free days is also associated with more ADHD symptoms. Stepwise multiple linear regression reveals that, when controlling for age and sex, SJL but not mid-sleep on free days is a significant predictor of ADHD symptoms and impulsivity. These results indicate that SJL may be an important factor to consider when exploring circadian rhythm associations with ADHD symptoms. PMID- 27668459 TI - A family harboring homozygous FZD4 deletion supports the existence of recessive FZD4-related familial exudative vitreoretinopathy. AB - PURPOSE: To document recessive FZD4-related familial exudative vitreoretinopathy. METHODS: Retrospective case series. RESULTS: Two brothers, the only two males among five siblings, had bilateral infantile retinal detachments and were referred for genetic counseling. Next-generation sequencing uncovered a homozygous FZD4 frameshift deletion in both affected brothers (c.40_49delCCCGGGGGCG; p.Pro14Serfs*44). None of the other immediate family members had clinical evidence for retinal disease, including the three family members who underwent confirmatory genetic testing and were found to be heterozygous for the mutation (both parents and one sister). CONCLUSIONS: The findings in this family support the concept that some mutated FZD4 alleles can be associated with recessive rather than dominant disease. PMID- 27668458 TI - In vitro circularization of RNA. AB - Over the past 2 decades, different types of circular RNAs have been discovered in all kingdoms of life, and apparently, those circular species are more abundant than previously thought. Apart from circRNAs in viroids and viruses, circular transcripts have been discovered in rodents more than 20 y ago and recently have been reported to be abundant in many organisms including humans. Their exact function remains still unknown, although one may expect extensive functional studies to follow the currently dominant research into identification and discovery of circRNA by sophisticated sequencing techniques and bioinformatics. Functional studies require models and as such methods for preparation of circRNA in vitro. Here, we will review current protocols for RNA circularization and discuss future prospects in the field. PMID- 27668460 TI - Attention Restoration Theory: A systematic review of the attention restoration potential of exposure to natural environments. AB - Attention Restoration Theory (ART) suggests the ability to concentrate may be restored by exposure to natural environments. Although widely cited, it is unclear as to the quantity of empirical evidence that supports this. A systematic review regarding the impact of exposure to natural environments on attention was conducted. Seven electronic databases were searched. Studies were included if (1) they were natural experiments, randomized investigations, or recorded "before and after" measurements; (2) compared natural and nonnatural/other settings; and (3) used objective measures of attention. Screening of articles for inclusion, data extraction, and quality appraisal were performed by one reviewer and checked by another. Where possible, random effects meta-analysis was used to pool effect sizes. Thirty-one studies were included. Meta-analyses provided some support for ART, with significant positive effects of exposure to natural environments for three measures (Digit Span Forward, Digit Span Backward, and Trail Making Test B). The remaining 10 meta-analyses did not show marked beneficial effects. Meta analysis was limited by small numbers of investigations, small samples, heterogeneity in reporting of study quality indicators, and heterogeneity of outcomes. This review highlights the diversity of evidence around ART in terms of populations, study design, and outcomes. There is uncertainty regarding which aspects of attention may be affected by exposure to natural environments. PMID- 27668461 TI - HSV2 reactivation and myelitis following influenza vaccination. AB - We report the case of a 57 year-old woman who developed transverse myelitis and acute HSV-2 reactivation following influenza vaccination. Over the next 5 years, she experienced a fluctuating course of improvement and regression for both myelitis and herpes. PMID- 27668464 TI - ? PMID- 27668463 TI - Modeling the Effects of Morphine on Simian Immunodeficiency Virus Dynamics. AB - Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses. Based on the small sample size Akaike information criterion, these models were inferior to the new model based on changes in co-receptor expression. The model with morphine affecting co-receptor expression agrees well with the experimental data from simian immunodeficiency virus infections in morphine-addicted macaques. Our results show that morphine promotes a target cell subpopulation switch from a lower level of susceptibility to a state that is about 2-orders of magnitude higher in susceptibility to SIV infection. As a result, the proportion of target cells with higher susceptibility remains extremely high in morphine conditioning. Such a morphine-induced population switch not only has adverse effects on the replication rate, but also results in a higher steady state viral load and larger CD4 count drops. Moreover, morphine conditioning may pose extra obstacles to controlling viral load during antiretroviral therapy, such as pre-exposure prophylaxis and post infection treatments. This study provides, for the first time, a viral dynamics model, viral dynamics parameters, and related analytical and simulation results for SIV dynamics under drugs of abuse. PMID- 27668462 TI - Lrp5/beta-Catenin Signaling Controls Lung Macrophage Differentiation and Inhibits Resolution of Fibrosis. AB - Previous studies established that attenuating Wnt/beta-catenin signaling limits lung fibrosis in the bleomycin mouse model of this disease, but the contribution of this pathway to distinct lung cell phenotypes relevant to tissue repair and fibrosis remains incompletely understood. Using microarray analysis, we found that bleomycin-injured lungs from mice that lack the Wnt coreceptor low density lipoprotein receptor-related protein 5 (Lrp5) and exhibit reduced fibrosis showed enrichment for pathways related to extracellular matrix processing, immunity, and lymphocyte proliferation, suggesting the contribution of an immune-matrix remodeling axis relevant to fibrosis. Activation of beta-catenin signaling was seen in lung macrophages using the beta-catenin reporter mouse, Axin2+/LacZ. Analysis of lung immune cells by flow cytometry after bleomycin administration revealed that Lrp5-/- lungs contained significantly fewer Siglec Flow alveolar macrophages, a cell type previously implicated as positive effectors of fibrosis. Macrophage-specific deletion of beta-catenin in CD11ccre;beta-cateninflox mice did not prevent development of bleomycin-induced fibrosis but facilitated its resolution by 8 weeks. In a nonresolving model of fibrosis, intratracheal administration of asbestos in Lrp5-/- mice also did not prevent the development of fibrosis but hindered the progression of fibrosis in asbestos-treated Lrp5-/- lungs, phenocopying the findings in bleomycin-treated CD11ccre;beta-cateninflox mice. Activation of beta-catenin signaling using lithium chloride resulted in worsened fibrosis in wild-type mice, further supporting that the effects of loss of Lrp5 are directly mediated by Wnt/beta-catenin signaling. Together, these data suggest that lung myeloid cells are responsive to Lrp5/beta-catenin signaling, leading to differentiation of an alveolar macrophage subtype that antagonizes the resolution of lung fibrosis. PMID- 27668465 TI - A New IMIA Tradition. PMID- 27668466 TI - Sharing Knowledge and Information. PMID- 27668467 TI - The Unified Medical Language System. AB - In 1986, the National Library of Medicine began a long-term research and development project to build the Unified Medical Language System(r) (UMLS(r)). The purpose of the UMLS is to improve the ability of computer programs to "understand" the biomedical meaning in user inquiries and to use this understanding to retrieve and integrate relevant machine-readable information for users. Underlying the UMLS effort is the assumption that timely access to accurate and up-to-date information will improve decision making and ultimately the quality of patient care and research. The development of the UMLS is a distributed national experiment with a strong element of international collaboration. The general strategy is to develop UMLS components through a series of successive approximations of the capabilities ultimately desired. Three experimental Knowledge Sources, the Metathesaurus(r), the Semantic Network, and the Information Sources Map have been developed and are distributed annually to interested researchers, many of whom have tested and evaluated them in a range of applications. The UMLS project and current developments in high-speed, high capacity international networks are converging in ways that have great potential for enhancing access to biomedical information. PMID- 27668469 TI - Standardization in Medical Informatics. AB - This article stresses the importance of standardization in the domain of Health and Medical Informatics, and Telematics. It gives an overview of the current standing of the activities of CEN TC 251 (European Standardization Committee, Technical Committee on Health Care informatics) and describes the scope and content of a number of emerging European standards. PMID- 27668468 TI - Security in Medical Information Systems. AB - This review article addresses security in medical information systems. First, it is discussed why special attention is necessary for security in this field. Next, the history is considered, together with the role of IMIA. Current research issues are presented. The ongoing activities in the AIM SEISMED project are briefly described, followed by a consideration of standardization. The article concludes with an appeal to pay more attention to the security aspects of information systems. PMID- 27668470 TI - Health and Clinical Management. PMID- 27668471 TI - Integrated Information Systems. PMID- 27668472 TI - Patient Record Systems. PMID- 27668473 TI - Image and Signal Processing. PMID- 27668474 TI - Decision Support Systems. PMID- 27668475 TI - Knowledge-Based Systems. PMID- 27668476 TI - Editorial Opinion: Qualifying the Use of "Only" in Your Job Description. PMID- 27668477 TI - A Meta-analysis to Evaluate the Predictive Validity of the Braden Scale for Pressure Ulcer Risk Assessment in Long-term Care. AB - Although it is among the most commonly used pressure ulcer risk assessment tools, the Braden Scale may lack strong predictive validity when used in the long-term care setting. A meta-analysis was conducted of English-language articles published in the PubMed database and Web of Science from the indices' inception through July 2015 to assess the predictive validity of the Braden Scale for pressure ulcers in long-term care residents. Search terms included pressure ulcer, pressure sore, bedsore, decubitus, long-term care, nursing home, skilled nursing facility, hospice, and Braden. Data extracted from the publications included sample and setting characteristics and predictive value indices. The pooled sensitivities, specificities, diagnostic odds ratios (DOR), and constructed summary receiver operating characteristic (SROC) curves were calculated. Eight studies (2 prospective cohorts and 6 cross-sectional studies) with 41 489 residents met selection criteria for inclusion in the analysis. The pooled sensitivity and specificity were 0.80 (95% CI: 0.79-0.81) and 0.42 (95% CI: 0.42-0.43), respectively, yielding a combined DOR of 5.66 (95% CI: 3.77 8.48). The area under the ROC curve (AUC) was 0.7686 +/- 0.0478 (95% CI: 0.6749 0.8623), and the overall diagnostic accuracy (Q*) was 0.7090 +/- 0.0402 (95% CI: 0.6302-0.7878). Significant heterogeneity was noted among the included studies; Q value was 302.54 (P = 0.000), and I2 for pooled sensitivity, pooled specificity, and pooled DOR was 97.4%, 98.7% and 96.4%, respectively. Meta-regression analysis showed no heterogeneity was noted among Braden scale cut-offs (P = 0.123) and pressure ulcer prevalence P = 0.547). The evidence showed the Braden Scale has moderate predictive validity and low predictive specificity for pressure ulcers in long-term care residents. The development and testing of new risk assessment scales for this population is warranted. PMID- 27668478 TI - Negative Pressure Wound Therapy With Instillation and Dwell Time Used to Treat Infected Orthopedic Implants: A 4-patient Case Series. AB - Infection following orthopedic implants for bone fixation or joint replacement is always serious and may require removal of the osteosynthetic material. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is an emerging therapy for the treatment of complex wounds, including infected wounds with osteosynthetic material. The purpose of this case study was to evaluate the outcomes of 4 patients (1 man, 3 women; age range 49 to 71 years) with a postoperative wound infection (POWI) following fracture repair and internal fixation. All patients were at high risk for surgical complications, including infections. Standard infection treatments (antibiotics) had been unsuccessful. Based on the available literature, a NPWTi-d protocol was developed. Following surgical debridement, wounds were instilled with polyhexanide biguanide with a set dwell time of 15 minutes, followed by continuous NPWTi-d of -125 mm Hg for 4 hours. The system was changed every 3 to 4 days until sufficient granulation tissue was evident and negative pressure without instillation could be used. Systemic antibiotics were continued in all patients. Granulation tissue was found to be sufficient in 12 to 35 days in the 4 cases, no recurrence of infection was noted, and the osteosynthesis material remained in place. No adverse events were observed. Research is needed to compare the safety and effectiveness of this adjunct treatment in the management of challenging wounds to other patient and wound management approaches. PMID- 27668479 TI - Exploring the Effect of Educating Certified Nursing Assistants on Pressure Ulcer Knowledge and Incidence in a Nursing Home Setting. AB - The certified nursing assistant (CNA) is the caregiver who frequently identifies the first signs and symptoms of pressure ulcers (PUs) in the long-term care setting. A quality improvement effort was implemented to explore the effect of a 1-hour CNA education program about early identification, treatment, and prevention of PUs on PU knowledge, PU incidence, and PU prevention interventions, including skin checks. All 33 CNAs employed in a care facility for residents 55+ years old were invited to participate. CNA demographic and PU education variables were obtained. PU knowledge was assessed using the Pressure Ulcer Toolkit questionnaire before, immediately after, and 3 months following the educational intervention about PU prevention. PU incidence data were abstracted from monthly quality assurance reports for the 3 months pre-intervention and 3 months post intervention. Patient medical records were mined for data on turning/repositioning, skin checks, and informing care staff of suspicious areas of skin for the 3 months pre- and post educational intervention. Data for percent of short-stay residents (< 90 days) with PUs were collected via the quarterly Medicare Nursing Home Compare Quality Measures report for this facility before and 3 months after the educational intervention. Pre-intervention and post intervention PU incidence was statistically analyzed using the t-test. The CNA demographic survey was administered using an anonymous pencil-and-paper format and hand-tabulated by the primary investigator. Of the 31 CNAs surveyed (mean age 32 years [range 18-65], mean years of experience 7.7 years [SD = 8.1, range 0.5 40], 26 (84%) reported they received training regarding PU prevention in the classroom during their initial CNA training, and 81% received on-the-job training at some point in their careers regarding PU prevention. The Quality Indicator report showed a reduction from 5 PUs to 0 (12.3%) in the 3 months pre intervention to 0% in the 3 months post-intervention. CNA reporting of skin breakdown increased by 68% from 8 reports to 17. CNA training regarding PU identification and prevention measures did not significantly improve knowledge scores, but the rate of PU development was significantly lower and the number of documented skin assessments and PU interventions higher after the education program. Additional studies to evaluate the effect of CNA education on the rate of PU development in nursing homes are warranted. PMID- 27668480 TI - Topical Corticosteroid for the Treatment of Hypergranulation Tissue at the Gastrostomy Tube Insertion Site: A Case Study. AB - Hypergranulation tissue formation around a gastrostomy tube insertion site is a common feeding tube-related complication that affects patients who receive long term enteral nutrition. Some clinicians recommend use of a topical corticosteroid in patients with gastrostomy tube insertion site hypergranulation. However, documentation is scant regarding appropriate treatment for this condition. This case report describes a 67-year-old bedridden man with spinocerebellar degeneration who presented with hypergranulation at the site of the gastrostomy tube, inserted 1 week earlier. The tissue was raw and inflamed, with bleeding and exudation. The gastrostomy site was gently cleansed with gauze dampened with tap water, and topical 0.05% clobetasol propionate ointment was applied directly to the hypergranulation tissue twice daily. After 4 days of treatment, the hypergranulation tissue almost completely disappeared, redness markedly decreased, and bleeding and exudation ceased, with no recurrence observed during the 6 months of follow-up. This case study supports other reports that short-term corticosteroid treatment may be a safe, quick, noninvasive, and effective treatment for hypergranulation at the gastrostomy tube insertion site. Further studies are needed to evaluate the safety, effectiveness, appropriate dosage, and duration of topical corticosteroid for the treatment of hypergranulation tissue. PMID- 27668481 TI - Piloting systems reset path integration systems during position estimation. AB - During locomotion, individuals can determine their positions with either idiothetic cues from movement (path integration systems) or visual landmarks (piloting systems). This project investigated how these 2 systems interact in determining humans' positions. In 2 experiments, participants studied the locations of 5 target objects and 1 single landmark. They walked a path after the targets and the landmark had been removed and then replaced the targets at the end of the path. Participants' position estimations were calculated based on the replaced targets' locations (Mou & Zhang, 2014). In Experiment 1, participants walked a 2-leg path. The landmark reappeared in a different location during or after walking the second leg. The results showed that participants' position estimations followed idiothetic cues in the former case, but the displaced landmark in the latter case. In Experiment 2, participants saw the displaced landmark when they reached the end of the second leg and then walked a third leg without the view of the landmark. Participants were asked or not to point to 1 of the targets before they walked the third leg. The results showed that the initial position of the third leg was still influenced by the displaced landmark in the former case, but was determined by idiothetic cues in the latter case. These results suggest that the path integration system works dynamically and the piloting system resets the path integration system when people judge their positions in the presence of conflicting piloting cues. (PsycINFO Database Record PMID- 27668482 TI - The functional determinants of short-term memory: Evidence from perceptual-motor interference in verbal serial recall. AB - A functional, perceptual-motor, account of serial short-term memory (STM) is examined by investigating the way in which an irrelevant spoken sequence interferes with verbal serial recall. Even with visual list-presentation, verbal serial recall is particularly susceptible to disruption by irrelevant spoken stimuli that have the same identity as-but that are order-incongruent with-the to be-remembered items. We test the view that such interference is because of the obligatory perceptual organization of the spoken stimuli yielding a sequence that competes with a subvocal motor-plan assembled to support the reproduction of the to-be-remembered list. In support of this view, the interference can be eliminated without changing either the identities or objective serial order of the spoken stimuli but merely by promoting a subjective perceptual organization that strips them of their order-incongruent relation to the to-be-remembered list (Experiment 1). The interference is also eliminated if subvocal motor sequence planning is impeded via articulatory suppression (Experiment 2). The results are in line with the view that performance-limits in verbal serial STM are because of having to exploit perceptual and motor processes for purposes for which they did not evolve, not the inherently limited capacity of structures or mechanisms dedicated to storage. (PsycINFO Database Record PMID- 27668483 TI - On predicting form and meaning in a second language. AB - We used event-related potentials (ERP) to investigate whether Spanish-English bilinguals preactivate form and meaning of predictable words. Participants read high-cloze sentence contexts (e.g., "The student is going to the library to borrow a . . ."), followed by the predictable word (book), a word that was form related (hook) or semantically related (page) to the predictable word, or an unrelated word (sofa). Word stimulus onset synchrony (SOA) was 500 ms (Experiment 1) or 700 ms (Experiment 2). In both experiments, all nonpredictable words elicited classic N400 effects. Form-related and unrelated words elicited similar N400 effects. Semantically related words elicited smaller N400s than unrelated words, which however, did not depend on cloze value of the predictable word. Thus, we found no N400 evidence for preactivation of form or meaning at either SOA, unlike native-speaker results (Ito, Corley et al., 2016). However, non native speakers did show the post-N400 posterior positivity (LPC effect) for form related words like native speakers, but only at the slower SOA. This LPC effect increased gradually with cloze value of the predictable word. We do not interpret this effect as necessarily demonstrating prediction, but rather as evincing combined effects of top-down activation (contextual meaning) and bottom-up activation (form similarity) that result in activation of unseen words that fit the context well, thereby leading to an interpretation conflict reflected in the LPC. Although there was no evidence that non-native speakers preactivate form or meaning, non-native speakers nonetheless appear to use bottom-up and top-down information to constrain incremental interpretation much like native speakers do. (PsycINFO Database Record PMID- 27668484 TI - Rehearsal of to-be-remembered items is unnecessary to perform directed forgetting within working memory: Support for an active control mechanism. AB - Directed forgetting tasks instruct people to forget targeted memoranda. In the context of working memory, people attempt to forget representations that are currently held in mind. Here, we evaluated candidate mechanisms of directed forgetting within working memory, by (a) testing the influence of articulatory suppression, a rehearsal-reducing and attention-demanding secondary task, on directed forgetting efficacy, and by (b) assessing the ability of people to perform forgetting in the absence of to-be-remembered competitors to rehearse. In Experiment 1, articulatory suppression interfered with directed forgetting, increasing the proportion of false alarms to to-be-forgotten probes in the working memory phase and decreasing the magnitude of the directed forgetting effect as assessed by an incidental long-term memory recognition test. Experiment 2 replicated the effects of articulatory suppression and tested whether the simultaneous requirement to retain, and presumably rehearse, to-be-remembered items was necessary for successful forgetting. The long-term directed forgetting effect was equivalent whether or not participants had to-be-remembered items to rehearse during the working memory phase. Experiment 3 included an additional comparison condition and confirmed that articulatory suppression interfered with directed forgetting and that participants were as efficient at directed forgetting with and without competitors to remember. In combination, these experiments suggest that directed forgetting in working memory requires an active control process that is limited by articulatory suppression, and that the demand to remember a concurrent memory set is unnecessary for this control process to operate. (PsycINFO Database Record PMID- 27668485 TI - Rapid forgetting results from competition over time between items in visual working memory. AB - Working memory is now established as a fundamental cognitive process across a range of species. Loss of information held in working memory has the potential to disrupt many aspects of cognitive function. However, despite its significance, the mechanisms underlying rapid forgetting remain unclear, with intense recent debate as to whether it is interference between stored items that leads to loss of information or simply temporal decay. Here we show that both factors are essential and interact in a highly specific manner. Although a single item can be maintained in memory with high fidelity, multiple items compete in working memory, progressively degrading each other's representations as time passes. Specifically, interaction between items is associated with both worsening precision and increased reporting errors of object features over time. Importantly, during the period of maintenance, although items are no longer visible, maintenance resources can be selectively redeployed to protect the probability to recall the correct feature and the precision with which cued items can be recalled, as if it was the only item in memory. These findings reveal that the biased competition concept could be applied not only to perceptual processes but also to active maintenance of working memory representations over time. (PsycINFO Database Record PMID- 27668487 TI - Development and psychometric evaluation of the Assessment of Core CBT Skills (ACCS): An observation-based tool for assessing cognitive behavioral therapy competence. AB - This article outlines the development and psychometric evaluation of the Assessment of Core CBT Skills (ACCS) rating scale. The ACCS aims to provide a novel assessment framework to deliver formative and summative feedback regarding therapists' performance within observed cognitive-behavioral treatment sessions, and for therapists to rate and reflect on their own performance. Findings from 3 studies are outlined: (a) a feedback study (n = 66) examining content validity, face validity and usability; (b) a focus group (n = 9) evaluating usability and utility; and (c) an evaluation of the psychometric properties of the ACCS in real world cognitive behavioral therapy (CBT) training and routine clinical practice contexts. Results suggest that the ACCS has good face validity, content validity, and usability and provides a user-friendly tool that is useful for promoting self reflection and providing formative feedback. Scores on both the self and assessor rated versions of the ACCS demonstrate good internal consistency, interrater reliability, and discriminant validity. In addition, ACCS scores were found to be correlated with, but distinct from, the Revised Cognitive Therapy Scale (CTS-R) and were comparable to CTS-R scores in terms of internal consistency and discriminant validity. In addition, the ACCS may have advantages over the CTS-R in terms of interrater reliability of scores. The studies also provided insight into areas for refinement and a number of modifications were undertaken to improve the scale. In summary, the ACCS is an appropriate and useful measure of CBT competence that can be used to promote self-reflection and provide therapists with formative and summative feedback. (PsycINFO Database Record PMID- 27668486 TI - Verbalizing, visualizing, and navigating: The effect of strategies on encoding a large-scale virtual environment. AB - Using novel virtual cities, we investigated the influence of verbal and visual strategies on the encoding of navigation-relevant information in a large-scale virtual environment. In 2 experiments, participants watched videos of routes through 4 virtual cities and were subsequently tested on their memory for observed landmarks and their ability to make judgments regarding the relative directions of the different landmarks along the route. In the first experiment, self-report questionnaires measuring visual and verbal cognitive styles were administered to examine correlations between cognitive styles, landmark recognition, and judgments of relative direction. Results demonstrate a tradeoff in which the verbal cognitive style is more beneficial for recognizing individual landmarks than for judging relative directions between them, whereas the visual cognitive style is more beneficial for judging relative directions than for landmark recognition. In a second experiment, we manipulated the use of verbal and visual strategies by varying task instructions given to separate groups of participants. Results confirm that a verbal strategy benefits landmark memory, whereas a visual strategy benefits judgments of relative direction. The manipulation of strategy by altering task instructions appears to trump individual differences in cognitive style. Taken together, we find that processing different details during route encoding, whether due to individual proclivities (Experiment 1) or task instructions (Experiment 2), results in benefits for different components of navigation-relevant information. These findings also highlight the value of considering multiple sources of individual differences as part of spatial cognition investigations. (PsycINFO Database Record PMID- 27668490 TI - Effects of Lipid Supplements on Tear Biochemistry in Contact Lens Wearers. AB - PURPOSE: To establish the effect of lipid supplements on tear lipid biochemistry and their influence on lens wear comfort in habitual lens wearers. METHODS: Forty habitual soft contact lens wearers were recruited to a double-masked, randomized crossover trial. An emulsion drop containing phosphatidylglycerol (Systane Balance; Alcon) and a liposomal spray containing phosphatidylcholine (Tears again; BioRevive) along with saline placebos were used three times a day for 14 days with 48 hours of washout between each intervention. The Contact Lens Dry Eye Questionnaire categorized participants into symptomatic and asymptomatic wearers. Ocular comfort was measured using the Ocular Comfort Index. Basal tears (15 MUl from each eye) were collected with lenses in situ and assayed for the concentration and activity of phospholipase (sPLA2) and the concentration of a malondialdehyde (MDA). Electrospray ionization mass spectrometry characterized the tear lipidome. RESULTS: Neither of the lipid supplements improved lens wear comfort compared to baseline. The spray treatment did not affect the concentration of the majority of lipid classes either at day 1 or at day 14. Both the lipid and placebo drops resulted in increased concentration of several lipid classes after day 1 of use, but by day 14, the concentration of most of the lipid classes had returned to baseline levels. With the lipid spray, sPLA2 activity (0.38 +/- 0.2 vs. 0.73 +/- 0.6 mmol/min/ml, p = 0.03) and lysophosphatidylethanolamine (LPE) (1.3 +/- 0.5 vs. 2.7 +/- 0.07 pmol/MUl, p = 0.02) were higher in the symptomatic group compared to asymptomatic group at day 1 but not at day 14. The lipid drop resulted in increased LPE concentration in symptomatic wearers at day 1 (1.7 +/- 0.3 vs. 2.4 +/- 0.3 pmol/MUl, p = 0.01) and at day 14 (1.7 +/- 0.4 vs. 2.5 +/- 0.5 pmol/MUl, p = 0.04). Ocular comfort was inversely proportional to the level (r = -0.21, p = 0.007) and activity of sPLA2 (r = -0.20, p = 0.01). There was an association between sPLA2 and LPC (r = 0.41, p < 0.001) and LPE (r = 0.40, p = 0.001), and a negative association with (O acyl)-omega-hydroxy fatty acids (OAHFAs) (r = -0.30, p = 0.03) in tears. CONCLUSIONS: Contact lens wear comfort was associated with sPLA2 concentration and activity in tears. Lipid biochemistry was transiently influenced by exogenous supplements. Although the specific supplement formulations tested did not differ from placebo in this study, the results do suggest a potential role for lysophospholipids and OAHFAs in modulating symptoms during contact lens wear. PMID- 27668489 TI - Visual Acuity and Self-Reported Visual Function among Migrant Farmworkers. AB - PURPOSE: Visual impairment presents significant risks for occupational injuries among farmworkers, a vulnerable population with limited access to vision care. Although previous research has noted farmworkers' low lifetime experience with vision screening and high rates of complaints of eye ailments and poor vision, there have been few screening data collected to evaluate these self-reports. The objectives of this analysis are to (1) describe farmworker visual health using standardized visual acuity screening data and self-reported visual function, and (2) to compare the screening and self-report data. METHODS: Data are from a cross sectional study of eye health among Latino migrant farmworkers in North Carolina with uncorrected vision (n = 289). Workers were recruited using methods to achieve a representative sample of a hard-to-reach population. Visual acuity data were collected using Snellen Tumbling E charts for nearsightedness and farsightedness. Binocular data are reported here. Interviews were conducted to obtain personal characteristics and self-assessed visual function. RESULTS: About 75% of farmworkers reported never having had a vision screening. Based on binocular screening, 1.7% (distance vision) and 6.9% (near vision) had moderate to severe visual impairment (>20/40). Farmworkers self-reported poorer visual function, compared with screening results; only 36.4% reported good or very good vision. Sensitivity of distance and near vision self-reports were 60 and 20%, respectively, but specificity was high. CONCLUSIONS: This study confirms past reports of little vision screening among farmworkers. Visual impairment for distance is comparable to other studies of Latinos in the US, though these studies have not reported near vision. Self-reports of vision problems are not a sensitive measure of visual acuity among farmworkers. Screening is needed to identify visual impairment that can create occupational safety risks in this health disparate population. PMID- 27668491 TI - Tear Lipid Layer Thickness Change and Topical Anti-Glaucoma Medication Use. AB - PURPOSE: To investigate the effects of topical anti-glaucoma medications on tear lipid layer thickness (LLT) and the ocular surface. METHODS: This retrospective study examined ocular surface disease (OSD) subjects who had (n = 34) and who did not have (n = 51) open-angle glaucoma (OAG). OSD was evaluated with lipid layer thickness (using LipiView interferometer), tear breakup time (TBUT), total corneal and conjunctival staining (Oxford grading scale), and Ocular Surface Disease Index (OSDI). Four variables (total duration of anti-glaucoma medication use, duration of current anti-glaucoma medication use, total number of daily anti glaucoma medication drops applied, and total number of anti-glaucoma medications [bottles]) related to anti-glaucoma medication were used to verify associations with LLT. RESULTS: Among the parameters, only LLT showed significantly lower values in the OAG group. In both groups, total staining showed a significant negative correlation between LLT and TBUT. Only in the OAG group, the OSDI showed significant correlations with number of medications (r = 0.389, p = 0.012) and daily number of drops (r = 0.354, p = 0.02); LLT showed significant correlations with TBUT (r = 0.381, p = 0.026) and total medication duration (r = -0.387, p = 0.013). In multivariate analyses, TBUT and total medication duration showed significant correlations with LLT (p = 0.032 and p = 0.015, respectively) in the OAG group. CONCLUSIONS: Topically medicated OAG subjects with OSD had a lower tear LLT than those with OSD who did not have OAG. Therefore, our results indicate that one should evaluate ocular surface disease status in patients who take anti-glaucoma medications. PMID- 27668492 TI - Holographic Refraction and the Measurement of Spherical Ametropia. AB - PURPOSE: To evaluate the performance of a holographic logMAR chart for the subjective spherical refraction of the human eye. METHODS: Bland-Altman analysis was used to assess the level of agreement between subjective spherical refraction using the holographic logMAR chart and conventional autorefraction and subjective spherical refraction. RESULTS: The 95% limits of agreement (LoA) were calculated between holographic refraction and the two standard methods (subjective and autorefraction). Holographic refraction has a lower mean spherical refraction when compared to conventional refraction (LoA 0.11 +/- 0.65 D) and when compared to autorefraction (LoA 0.36 +/- 0.77 D). After correcting for systemic bias, this is comparable between autorefraction and conventional subjective refraction (LoA 0.45 +/- 0.79 D). After correcting for differences in vergence distance and chromatic aberration between holographic and conventional refraction, approximately 65% (group 1) of measurements between holography and conventional subjective refraction were similar (MD = 0.13 D, SD = 0.00 D). The remaining 35% (group 2) had a mean difference of 0.45 D (SD = 0.12 D) between the two subjective methods. Descriptive statistics showed group 2's mean age (21 years, SD = 13 years) was considerably lower than group 1's mean age (41 years, SD = 17), suggesting accommodation may have a role in the greater mean difference of group 2. CONCLUSIONS: Overall, holographic refraction has good agreement with conventional refraction and is a viable alternative for spherical subjective refraction. A larger bias between holographic and conventional refraction was found in younger subjects than older subjects, suggesting an association between accommodation and myopic over-correction during holographic refraction. PMID- 27668494 TI - Type II Macular Telangiectasia Presenting as Bilateral Retinochoroidal Anastomosis. AB - PURPOSE: Retinochoroidal anastamosis (RCA) is known to be associated with retinal angiomatous proliferans rather than idiopathic macular telangiectasia. The case report describes a rare association of bilateral RCA with type II idiopathic macular telangiectasia in an elderly woman. CASE REPORT: A 65-year-old female patient presented with decreased vision in both eyes to the ophthalmology clinic. She was diagnosed with bilateral large serous retinal pigment epithelial detachments (PED). Atypical association of PED with IMT led to additional imaging, including fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), and indocyanine green angiography (ICGA). Multimodal imaging analysis revealed characteristic signs of RCA such as the so called kissing sign on SD-OCT. The patient was not offered any treatment due to the poor prognosis associated with the condition. CONCLUSIONS: Although more commonly associated with retinal angiomatous proliferans (type III neovascular age-related macular degeneration), RCA can present in type II IMT Stage 5. PMID- 27668495 TI - Regressive Retinal Flecks in CRX-Mutated Early-Onset Retinal Dystrophy. AB - PURPOSE: To describe a peculiar flecked-retina phenotype in a young female affected by early-onset retinal dystrophy due to a heterozygous mutation in the cone-rod transcription factor CRX gene. CASE REPORT: A 5-year-old girl presented with poor vision and nystagmus from the first month after birth. Opththalmologic examination at baseline revealed an altered foveal reflex, epiretinal membrane, and yellow fleck-like retinal deposits in the mid- and extreme periphery bilaterally that disappeared after 3 years of follow-up. Electoretinogram was non recordable in both rods and cones components bilaterally. Genomic sequencing identified a heterozygous missense mutation -c.425A > G (Tyr142Cys) in CRX. CONCLUSIONS: We identified a novel early-onset retinal dystrophy-related heterozygous CRX mutation associated with early and severe rod and cone dysfunction and regressive flecked-retina appearance on ophthalmoscopy. PMID- 27668493 TI - In Vivo Angiography Quantifies Oxygen-Induced Retinopathy Vascular Recovery. AB - PURPOSE: Retinopathy of prematurity (ROP) is a potentially blinding vasoproliferative disease. There is no standardized way to quantify plus disease (tortuous and dilated retinal vessels) or characterize abnormal recovery during ROP monitoring. This study objectively studies vascular features in live mice during development using noninvasive retinal imaging. METHODS: Using fluorescein angiography (FA), retinal vascular features were quantified in live mice with oxygen induced retinopathy (OIR). A total of 105 wild-type mice were exposed to 77% oxygen from postnatal day 7 (P7) till P12 (OIR mice). Also, 105 age-matched pups were raised in room air (RA mice). In vivo FA was performed at early (P16 to P20), mid (P23 to P27), late (P30 to P34), and mature (P47) phases of retinal vascular development. Retinal vascular area, retinal vein width, and retinal artery tortuosity were quantified. RESULTS: Retinal artery tortuosity was higher in OIR than RA mice at early (p < 0.0001), mid (p < 0.0001), late (p < 0.0001), and mature (p < 0.0001) phases. Retinal vascular area in OIR mice increased from early to mid-phase (p < 0.0001), but remained unchanged from mid to late (p = 0.23), and from late to mature phase (p = 0.98). Retinal vein width was larger in OIR mice compared to RA mice during early phase only. Arteries in OIR mice were more tortuous from early to mid-phase (p < 0.0001), but tortuosity remained stable from mid through mature phase. RA mice had an increase in retinal vascular area from early to late phase, but maintained uniform retinal vein width and retinal artery tortuosity in all phases. CONCLUSIONS: In vivo FA distinguished arterial and venous features, similar to plus disease, and revealed aberrant recovery of OIR mice (arterial tortuosity, reduced capillary density, and absent neovascular buds) that persisted into adulthood. Retinal artery tortuosity may be a reliable, objective marker of severity of ROP. Infants with abnormal retinal vascular recovery may need extended monitoring. PMID- 27668496 TI - Five-Year PROSE Treatment for Aniridic Keratopathy. AB - PURPOSE: Aniridic keratopathy is vision-threatening condition in patients with aniridia. The keratopathy occurs due to limbal stem cell deficiency. When conventional treatments fail, surgical treatments such as corneal limbal transplantation or cultivated oral mucosal epithelium transplantation are the alternatives. Here, we report our experience with the management and monitoring of the progress of a case with aniridic keratopathy treated with a scleral lens. CASE REPORT: We describe the case of a 30-year-old woman with aniridic keratopathy in both eyes. She visited our outpatient clinic for treatment of visual disturbances in her left eye, which showed a 360 degrees invasion of the conjunctiva. Despite conventional treatment with artificial tears and autologous serum eye drops, the left eye started to suffer from recurrent corneal erosions at 19 months after the initial visit. At 50 months after the initial visit, it presented with persistent epithelial defects and decrease in vision because of the invasion of the vascularized conjunctiva with subepithelial fibrosis. Upon concluding that conventional treatment was ineffective, we tried using a scleral lens (Prosthetic Replacement of the Ocular Surface Ecosystem; PROSE). After the scleral lens treatment, the epithelial defect quickly healed, and visual acuity improved. Six years after the initial visit, the patient's right eye also started to show epithelial irregularities, which were also treated with a scleral lens. The visual acuity in the right eye too recovered, and corneal transparency was maintained until 3 years after the scleral lens treatment. CONCLUSIONS: The current case showed that long-term scleral lens treatment is a promising option to maintain a healthy ocular surface and visual function in eyes with aniridia caused by limbal stem cell deficiency. Early treatment with a scleral lens may be beneficial in preventing stromal scar formation in the cornea affected by aniridic keratopathy. PMID- 27668497 TI - Bilateral Corneal Epithelial Lesions Associated with Paclitaxel. AB - PURPOSE: An antineoplastic drug, paclitaxel, is widely used in small cell lung cancer, breast cancer, and ovarian cancer. We report a case of bilateral, vision impairing corneal epithelial lesions that developed in a patient receiving paclitaxel monotherapy for breast cancer. CASE REPORT: A 45-year-old woman presented with a 1-month history of bilateral visual disturbances. She had been receiving paclitaxel chemotherapy after modified radical mastectomy for invasive ductal carcinoma in her left breast. Best-corrected visual acuity was 20/100 in the right eye and 20/40 in the left eye. Slit-lamp examination revealed irregular triangular corneal lesions in both eyes. The lesions extended to the center of the cornea involving the visual axis and showed late staining with fluorescein dye. The lesions resolved 5 months after discontinuation of paclitaxel chemotherapy, and best-corrected visual acuity was restored to 20/20 in both eyes. CONCLUSIONS: Microtubule-stabilizing chemotherapeutic drugs such as paclitaxel can cause visually significant corneal lesions, and these lesions appear to be reversible with discontinuation of the drug. This case highlights the need for regular ophthalmologic examinations for the detection of this reversible adverse ocular reaction. PMID- 27668499 TI - UNILATERAL BEST DISEASE: A CASE REPORT. AB - PURPOSE: To describe the multimodal imaging findings observed unilaterally in a patient with Best disease due to a p.G15D mutation in the BEST1 gene. METHODS: The clinical history of a 62-year-old female patient with unilateral Best disease was reviewed. Retinal findings were documented by clinical examination and multimodal imaging. RESULTS: Posterior segment examination of the patient's right eye demonstrated retinal pigment epithelium hypopigmentation and clumping in the central macula beneath a chronic shallow serous retinal detachment (SRD), confirmed by optical coherence tomography. Fluorescein angiography showed central staining with no evidence of focal leakage or choroidal neovascularization, and correlated with the hypoautofluorescence seen on fundus autofluorescence. There was no evidence of choroidal hyperpermeability on indocyanine green angiography, nor was there any neovascularization detected on optical coherence tomography angiography. The left eye appeared normal with all imaging modalities. CONCLUSION: Best disease is an autosomal dominant disease that is generally bilateral. We present a case of a unilateral Best disease with serous retinal detachment in a patient with a p.G15D mutation in BEST1. Best disease should be considered in the differential diagnosis of serous retinal detachment and may masquerade as central serous chorioretinopathy. PMID- 27668500 TI - PARACENTRAL ACUTE MIDDLE MACULOPATHY AND DEEP RETINAL CAPILLARY PLEXUS INFARCTION SECONDARY TO REPERFUSED CENTRAL RETINAL ARTERY OCCLUSION. AB - PURPOSE: To report a case of reperfused central retinal artery occlusion causing a globular pattern of paracentral acute middle maculopathy with en face optical coherence tomography (OCT). METHODS: Retrospective case report. Widefield fluorescein angiography, en face OCT, and OCT-angiography were performed. Retinal capillary plexus vessel density (mm) was measured using OCT-angiography analysis and was defined as total vessel length (mm) per area (mm). RESULTS: A 76-year-old female presented with decreased vision in the left eye for 1 day. Widefield fluorescein angiography revealed delayed venous filling in the early phase and selective arterial staining in the late phase. Spectral domain OCT demonstrated paracentral acute middle maculopathy. Optical coherence tomography-angiography showed an ischemic deep retinal capillary plexus that colocalized with a globular shaped hyper-reflective pattern identified with structural en face OCT. Quantitative vessel density analysis comparing the fellow eye to the affected eye at presentation demonstrated 43% reduction in the superficial capillary plexus vessel density and 33% reduction of the deep capillary plexus in the affected eye. At 2 months follow-up, the reduction of superficial capillary plexus vessel density improved to 33%, whereas the deep capillary plexus vessel density reduced further to 35% compared with the fellow eye. CONCLUSION: The authors report a case of reperfused central retinal artery occlusion leading to a globular shaped paracentral acute middle maculopathy lesion with en face OCT. Quantitative OCT angiography vessel density analysis in the chronic phase revealed disproportionate reduction of deep capillary plexus vessel density. The globular pattern of paracentral acute middle maculopathy with en face OCT can be an important clue to the diagnosis of central retinal artery occlusion. PMID- 27668501 TI - CILIOCHOROIDAL EFFUSION AND ACUTE MACULAR NEURORETINOPATHY ASSOCIATED WITH CERVICAL TRACTION THERAPY. AB - PURPOSE: To report an unusual case of ciliochoroidal effusion and presumed acute macular neuroretinopathy associated with cervical traction therapy for the treatment of cervical spinal stenosis. METHODS: Case report. RESULTS: A 75-year old man reported sudden onset of a wedge-shaped paracentral scotoma in the right eye. Fundus examination showed a ciliochoroidal effusion in the right eye. Optical coherence tomography revealed intraretinal fluid in both eyes without leakage on fluorescein angiography. B-scan ultrasonography and anterior segment ultrasound biomicroscopy of the right eye showed peripheral ciliochoroidal effusion. He had recently started intensive cervical traction therapy for the treatment of cervical spinal stenosis. There was spontaneous resolution of the choroidal effusion and intraretinal fluid after stopping cervical traction treatments. Optical coherence tomography imaging after resolution of the intraretinal fluid revealed thinning of the outer nuclear layer and attenuation of the ellipsoid and interdigitation zones corresponding to a persistent paracentral scotoma, consistent with acute macular neuroretinopathy. CONCLUSION: This is the first report of adverse ocular effects of cervical traction. We postulate that venous and arterial compromise during cervical traction therapy resulted in both ciliochoroidal effusion and a watershed infarct in the outer retina. PMID- 27668502 TI - CONGENITAL CONTRACTILE PERIPAPILLARY STAPHYLOMA WITH RHEGMATOGENOUS RETINAL DETACHMENT. AB - PURPOSE: To describe the occurrence of a congenital contractile peripapillary staphyloma in association with a rhegmatogenous retinal detachment. METHODS: The clinical course of a 17-year-old patient with a contractile peripapillary staphyloma and undergoing pars plana vitrectomy for repair of an associated retinal detachment was studied. RESULTS: The left eye showed a peripapillary staphyloma which during the ophthalmoscopical examination revealed contractile movements after the presentation of a light stimulus to either eye. The contraction of the peripapillary staphyloma was not correlated with a Valsalva maneuver, neck venous compression, forced lid closure, or respiratory movements. Because of a retinal detachment involving the inferior, nasal, and temporal retina, best-corrected visual acuity was 20/100. During pars plana vitrectomy under systemic anesthesia, the contractions of the peripapillary staphyloma subsided in the early phase of surgery, and reoccurred at approximately 80 minutes after the start of general anesthesia, when the posterior pole was touched with an aspiration syringe. CONCLUSION: The etiology of the movements of the congenital peripapillary staphyloma in our patient may include a misbalance between intraocular pressure and orbital cerebrospinal fluid pressure or contractions of extraocular muscles. The observations may give information about the physiology and pathophysiology of the optic nerve head. PMID- 27668503 TI - Are Early Career Orthopaedic Trauma Surgeons Performing Less Complex Trauma Surgery? AB - PURPOSE: There has recently been an increase in the number of fellowship trained orthopaedic trauma surgeons, raising concerns that the surgical experience of early career surgeons may be diluted. We sought to evaluate the change in complex trauma case volume of orthopaedic trauma surgeons sitting for Part II of the American Board of Orthopaedic Surgeons certification examination. METHODS: The case log data from all surgeons taking Part II of the American Board of Orthopaedic Surgeons examination over a 13-year period (2003-2015) was evaluated. Any surgeon who examined in the trauma subspecialty was included. We defined pelvis, acetabulum, and periarticular fracture surgeries as complex trauma procedures and evaluated changes in case volume over time. RESULTS: We included 468 candidates who examined as trauma subspecialists and performed 90,261 procedures. The number of candidates testing in trauma per year ranged from 15 to 65 and increased significantly over time [beta = 4.05 (0.37), P < 0.0001]. Their case volume was stable over time [beta = -1.7 (1.1), P = 0.16]. The number of acetabulum fracture surgeries performed decreased significantly over time from a mean of 10.1 cases in 2003 to 5.2 cases in 2015 [beta = -0.34 (0.08), P = 0.0015]. There was no significant change in the number of pelvic fracture surgeries [beta = -0.1 (0.1), P = 0.285]. There was a trend toward less periarticular fracture surgeries [beta = -0.3 (0.1), P = 0.072]. CONCLUSIONS: Although pelvic ring and periarticular fracture case volume have remained stable, early career surgeons have experienced a significant decrease in acetabular fracture case volume. The implications of this decreased surgical experience warrant careful consideration as the orthopaedic trauma workforce evolves. PMID- 27668504 TI - Alignment After Intramedullary Nailing of Distal Tibia Fractures Without Fibula Fixation. AB - OBJECTIVE: To evaluate the efficacy of intramedullary nailing of distal tibia fractures using modern techniques, without fibula fixation, in obtaining and maintaining alignment. DESIGN: Retrospective case review. SETTING: Level-I academic trauma center. PATIENTS: One hundred thirty-two consecutive patients with distal tibia fractures. INTERVENTION: Intramedullary nail of distal tibia fracture, without fibula fixation, was performed in consecutive patients using modern reduction techniques. MAIN OUTCOME MEASURES: Malalignment and malunion were defined as >5 degrees of varus/valgus angulation or anterior/posterior angulation on the initial postoperative or final anteroposterior and lateral x rays. RESULTS: There were 122 consecutive patients (86 men and 36 women) 16-93 years of age (average, 43 years) with 36 (30%) open and 85 (70%) closed fractures with complete follow-up. Mechanism of injury did not predict the presence or level of fibula fracture. Upon presentation, varus/valgus and procurvatum/recurvatum angulation was greatest when the fibula was fractured at the level of the tibia fracture (P = 0.001 and 0.028). The most common intraoperative reduction aids were nailing in relative extension, transfixion external fixation, and clamps at the fracture site. The OTA fracture type or level/presence of fibula fracture did not influence malalignment (P = 0.86 and 0.66), malunion (P = 0.81 and 0.79), or the change in alignment during union, which averaged 0.9 degrees. CONCLUSIONS: We found an overall low rate of both malalignment (2%) and malunion (3%) after intramedullary nailing of distal tibial shaft fracture without fibula fixation. We conclude that when modern nailing techniques are used, which allow for confirmation of reduction by visualization in fluoroscopy, from nail placement to distal interlocking, fibula fixation is not necessary to obtain or maintain alignment. Furthermore, standard 2 medial to lateral screws distally afford adequate stability to hold the reduction during union with a 0.9-degree difference in the initial postoperative and final united films. LEVEL OF EVIDENCE: Therapeutic level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27668505 TI - The Utility of the Tip-Apex Distance in Predicting Axial Migration and Cutout With the Trochanteric Fixation Nail System Helical Blade: Erratum. PMID- 27668506 TI - One-Step Maxillary Sinus Augmentation in Association With Endoscopic Sinus Surgery: Case Series and Review of the Literature. AB - INTRODUCTION: Sinonasal anatomical anomalies and inflammatory conditions may reduce success rates of maxillary sinus elevation (MSE) procedures used to allow implant placement in the atrophic posterior maxilla. Approaches combining endoscopic sinus surgery (ESS) and MSE were firstly proposed by our group and have already been described in the literature. This article aims to re-evaluate the procedure in a larger sample of patients comparing results and indications with the pertaining literature. MATERIALS AND METHODS: Thirty-three patients (19 men and 14 women, mean age 52.79 +/- 11.95 years) underwent combined ESS/MSE with 48 MSE procedures performed. RESULTS: No intraoperative complications were reported. An uneventful and complete graft integration was obtained after 6 months in all but one patient. All patients completed prosthetic rehabilitation within 9 to 12 months. CONCLUSION: Combined ESS and MSE has proven to be a safe and reliable procedure, which can be proposed to selected patients presenting with reversible sinonasal contraindications to MSE and should be no more considered an experimental procedure. PMID- 27668507 TI - The roles of acculturative stress and social constraints on psychological distress in Hispanic/Latino and Asian immigrant college students. AB - OBJECTIVES: Acculturative stress has been linked to psychological distress, but few studies have explored the moderating role of social constraints on this relationship. Social constraints are the perception that social networks are unsupportive to stressor-related discussions. In the present study, the relationship between acculturative stress and psychological distress in Hispanic/Latino and Asian immigrants and the moderating role of social constraints in this relationship were examined. METHOD: Participants were 306 college students (169 Hispanics/Latinos, 137 Asians; 33.9% first-generation immigrants, 66.1% second-generation immigrants) from two Texas universities. RESULTS: Correlation results showed that acculturative stress and social constraints were significantly associated with higher levels of psychological distress in Hispanics/Latinos and Asians. In addition, regression results indicated a significant three-way interaction effect among acculturative stress, social constraints, and racial/ethnic groups. Social constraints were found to moderate the relationship between acculturative stress and psychological distress in Asians but not in Hispanics/Latinos. Significant association between acculturative stress and psychological distress was found in Asians with higher levels of social constraints but not in Asians with lower levels of social constraints. CONCLUSIONS: These findings suggested that the interaction effect of acculturative stress and social constraints on psychological distress may be subject to cultural influences, and social constraints may have differential roles in Hispanics/Latinos and Asians. Potential implications on the development of culturally adaptive interventions for different racial/ethnic minority groups were discussed. (PsycINFO Database Record PMID- 27668508 TI - Surface-nitrogen-rich ordered mesoporous carbon as an efficient metal-free electrocatalyst for oxygen reduction reaction. AB - Exploring efficient metal-free electrocatalysts for oxygen reduction reactions (ORR) will have a great impact on the field of fuel cells and metal-air batteries. In this paper, we report a simple and efficient routine to coat ordered mesoporous carbon (CMK-3) with nitrogen-doped carbon via pyrolysis of the surface-self-polymerized polydopamine. The optimized CMK-3 catalyst with a coating of nitrogen-doped carbon demonstrates excellent electrocatalytic activity towards ORR in alkaline media. The coating procedure under optimized conditions lowers the ORR half-wave-potential by 80 mV, giving a genuine metal-free catalyst with an onset ORR potential of 0.96 V (vs reversible hydrogen electrode (RHE)) and half-wave potential of 0.83 V (vs RHE) in 0.1 M KOH, which is much better than other carbon material-based catalysts (such as carbon nanotubes and their composites). The performance of this surface-nitrogen-rich CMK-3 catalyst is also superior to that of N-doped ordered mesoporous carbon synthesized by means of the 'nanocasting' technique. Furthermore, the as-prepared catalyst performs comparably in terms of activity, superior durability, and higher tolerance to methanol compared with commercially available Pt/C. PMID- 27668509 TI - Enhancing the Dispersibility of TiO2 Nanorods and Gaining Control over Region Selective Layer Formation. AB - We demonstrate that the dispersibility and reactivity of core-shell TiO2 nanorods (NRs) can be controlled significantly through functionalization with a combination of ligands based on phosphonic acid derivatives (PAs). Specifically, a glycol based PA allows dispersion of the NRs in methanol (MeOH). On the other hand, incorporating an alkyne terminated PA in the ligand shell of the NRs allows for a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction with an azide patterned aluminum oxide (AlOx) substrate and forms a region-selectively deposited film of NRs. We clearly demonstrate that the quality of the NR films correlates strongly with the stability of the NR dispersions in the reaction medium. In particular, tuning the concentration of alkyne PA in the ligand shell inhibits aggregation of the NRs on the substrate, while reactivity for the CuAAC reaction is maintained. The surface coverage with NRs fits the Langmuir model. This study illustrates that surface functionalization of AlOx substrates can be effectively and conveniently controlled through enhancing the dispersibility of the NRs using mixed ligand shells. PMID- 27668510 TI - Optimization of Pore Structure of Cathodic Carbon Supports for Solvate Ionic Liquid Electrolytes Based Lithium-Sulfur Batteries. AB - Lithium-sulfur (Li-S) batteries are a promising energy-storage technology owing to their high theoretical capacity and energy density. However, their practical application remains a challenge because of the serve shuttle effect caused by the dissolution of polysulfides in common organic electrolytes. Polysulfide-insoluble electrolytes, such as solvate ionic liquids (ILs), have recently emerged as alternative candidates and shown great potential in suppressing the shuttle effect and improving the cycle stability of Li-S batteries. Redox electrochemical reactions in polysulfide-insoluble electrolytes occur via a solid-state process at the interphase between the electrolyte and the composite cathode; therefore, creating an appropriate interface between sulfur and a carbon support is of great importance. Nevertheless, the porous carbon supports established for conventional organic electrolytes may not be suitable for polysulfide-insoluble electrolytes. In this work, we investigated the effect of the porous structure of carbon materials on the Li-S battery performance in polysulfide-insoluble electrolytes using solvate ILs as a model electrolyte. We determined that the pore volume (rather than the surface area) exerts a major influence on the discharge capacity of S composite cathodes. In particular, inverse opal carbons with three dimensionally ordered interconnected macropores and a large pore volume deliver the highest discharge capacity. The battery performance in both polysulfide soluble electrolytes and solvate ILs was used to study the effect of electrolytes. We propose a plausible mechanism to explain the different porous structure requirements in polysulfide-soluble and polysulfide-insoluble electrolytes. PMID- 27668511 TI - Biological Membranes in Extreme Conditions: Anionic Tetraether Lipid Membranes and Their Interactions with Sodium and Potassium. AB - Archaea such as Sulfolobus acidocaldarius tolerate extreme temperatures and high acidity and can grow in the presence of toxic metals and low concentrations of Na+ or K+. It is believed that their unique tetraether membranes protect them from harsh environments and allow their survival under such conditions. We used molecular dynamics simulations to study membranes comprising glycerol dialkylnonitol tetraether lipids, which are the main component of S. acidocaldarius membranes, in solutions containing different concentrations of NaCl and KCl or with Na+ or K+ counterions (trace cations, 0 M). Anionic binding sites on the membranes were almost 50% occupied in the presence of counterions. The free energy of cation-phosphate complexation and the residence times of ions near the membranes were found to be both ion- and concentration-dependent. Sodium ions had more favorable interactions with the membranes and a longer residence time, whereas higher cation concentrations led to shorter ion residence times. When only counterions were present in the solutions, large residence times suggested that the membrane may function as a cation-attracting reservoir. The results suggested that the ions can be easily transferred to the cytoplasm as needed, explaining the growth curves of S. acidocaldarius under different salinities and pH. PMID- 27668512 TI - Orientational Dynamics of a Functionalized Alkyl Planar Monolayer Probed by Polarization-Selective Angle-Resolved Infrared Pump-Probe Spectroscopy. AB - Polarization-selective angle-resolved infrared pump-probe spectroscopy was developed and used to study the orientational dynamics of a planar alkylsiloxane monolayer functionalized with a rhenium metal carbonyl headgroup on an SiO2 surface. The technique, together with a time-averaged infrared linear dichroism measurement, characterized picosecond orientational relaxation of the headgroup occurring at the monolayer-air interface by employing several sets of incident angles of the infrared pulses relative to the sample surface. By application of this method and using a recently developed theory, it was possible to extract both the out-of-plane and "mainly"-in-plane orientational correlation functions in a model-independent manner. The observed correlation functions were compared with theoretically derived correlation functions based on several dynamical models. The out-of-plane correlation function reveals the highly restricted out of-plane motions of the head groups and also suggests that the angular distribution of the transition dipole moments is bimodal. The mainly-in-plane correlation function, for the sample studied here with the strongly restricted out-of-plane motions, essentially arises from the purely in-plane dynamics. In contrast to the out-of-plane dynamics, significant in-plane motions occurring over various time scales were observed including an inertial motion, a restricted wobbling motion of ~3 ps, and complete randomization occurring in ~25 ps. PMID- 27668513 TI - Enantioselective Synthesis of Polysubstituted Benzopyrano[3,4-c]pyrrolidine Frameworks via [3 + 2] Cycloaddition of Azomethine Ylides and Coumarin Derivatives. AB - An enantioselective synthesis of benzopyrano[3,4-c]pyrrolidine derivatives via organocatalyzed [3 + 2] cycloaddition has been achieved. Cinchona alkaloid derived organocatalysts as Bronsted bases have been examined for this asymmetric cycloaddition of o-hydroxy aromatic aldimines with 3-substituted coumarins. An unexpected rearrangement of the quaternary acyl moiety in the products resulted in an in situ protection of the o-hydroxy group. PMID- 27668514 TI - Proteins from the past. AB - Some fragments of ancient protein are less prone to degradation because they bind strongly to the surfaces of minerals. PMID- 27668516 TI - Relativistic Two-Component Particle-Particle Tamm-Dancoff Approximation. AB - With the recent introduction of the particle-particle random-phase and Tamm Dancoff approximations to ab initio theory, routine queries of traditionally difficult systems, such as diradicals and doubly excited states, have been made possible. However, although a wealth of inquiry has been directed to investigating these methods, the current formulations have been restricted to spin-collinear systems, leaving the methods incapable of treating noncollinearity and spin-orbit relativistic effects in excited states. In this work, we extend the particle-particle Tamm-Dancoff approximation to suit two-component Hamiltonians to explicitly treat relativistic effects in excited states. After reviewing the theory and computational implementation, we demonstrate the accuracy of this extension by evaluating the fine structure splittings some of atomic and molecular systems. PMID- 27668517 TI - Room Temperature Catalyst System for the Hydroarylation of Olefins. AB - A simple protocol for the hydroarylation of olefins to yield diarylmethine products is described. A Friedel-Crafts-type synthetic strategy allows direct access to biorelevant products in high atom efficiency. A combination of substoichiometric amounts of TMSCl and ZnBr2 promotes a rapid hydroarylation process at ambient temperature. The method is high yielding and is amenable to scale-up protocols. PMID- 27668518 TI - Graphene as a Promising Electrode for Low-Current Attenuation in Nonsymmetric Molecular Junctions. AB - We have measured the single-molecule conductance of 1,n-alkanedithiol molecular bridges (n = 4, 6, 8, 10, 12) on a graphene substrate using scanning tunneling microscopy (STM)-formed electrical junctions. The conductance values of this homologous series ranged from 2.3 nS (n = 12) to 53 nS (n = 4), with a decay constant betan of 0.40 per methylene (-CH2) group. This result is explained by a combination of density functional theory (DFT) and Keldysh-Green function calculations. The obtained decay, which is much lower than the one obtained for symmetric gold junctions, is related to the weak coupling at the molecule graphene interface and the electronic structure of graphene. As a consequence, we show that using graphene nonsymmetric junctions and appropriate anchoring groups may lead to a much-lower decay constant and more-conductive molecular junctions at longer lengths. PMID- 27668515 TI - Protein sequences bound to mineral surfaces persist into deep time. AB - Proteins persist longer in the fossil record than DNA, but the longevity, survival mechanisms and substrates remain contested. Here, we demonstrate the role of mineral binding in preserving the protein sequence in ostrich (Struthionidae) eggshell, including from the palaeontological sites of Laetoli (3.8 Ma) and Olduvai Gorge (1.3 Ma) in Tanzania. By tracking protein diagenesis back in time we find consistent patterns of preservation, demonstrating authenticity of the surviving sequences. Molecular dynamics simulations of struthiocalcin-1 and -2, the dominant proteins within the eggshell, reveal that distinct domains bind to the mineral surface. It is the domain with the strongest calculated binding energy to the calcite surface that is selectively preserved. Thermal age calculations demonstrate that the Laetoli and Olduvai peptides are 50 times older than any previously authenticated sequence (equivalent to ~16 Ma at a constant 10 degrees C). PMID- 27668519 TI - 5-Substituted Pyrimidine and 7-Substituted 7-Deazapurine dNTPs as Substrates for DNA Polymerases in Competitive Primer Extension in the Presence of Natural dNTPs. AB - A complete series of 5-substituted uracil or cytosine, as well as 7-substituted 7 deazaadenine and 7-deazaguanine 2'-deoxyribonucleoside triphosphates (dNTPs) bearing substituents of increasing bulkiness (H, Me, vinyl, ethynyl, and phenyl) were systematically studied in competitive primer extension in the presence of their natural counterparts (nonmodified dNTPs), and their kinetic data were determined. The results show that modified dNTPs bearing pi-electron-containing substituents (vinyl, ethynyl, Ph) are typically excellent substrates for DNA polymerases comparable to or better than natural dNTPs. The kinetic studies revealed that these modified dNTPs have higher affinity to the active site of the enzyme-primer-template complex, and the calculations (semiempirical quantum mechanical scoring function) suggest that it is due to the cation-pi interaction of the modified dNTP with Arg629 in the active site of Bst DNA polymerase. PMID- 27668520 TI - A Novel Mechanism for Chemical Sensing Based on Solvent-Fluorophore-Substrate Interaction: Highly Selective Alcohol and Water Sensor with Large Fluorescence Signal Contrast. AB - Differentiation of solvents having similar physicochemical properties, such as ethanol and methanol, is an important issue of interest. However, without performing chemical analyses, discrimination between methanol and ethanol is highly challenging due to their similarity in chemical structure as well as properties. Here, we present a novel type of alcohol and water sensor based on the subtle differences in interaction among solvent analytes, fluorescent organic molecules, and a mesoporous silica gel substrate. A gradual change in the chemical structure of the fluorescent diketopyrrolopyrrole (DPP) derivatives alters their interaction with the substrate and solvent analyte, which creates a distinct intermolecular aggregation of the DPP derivatives on the silica gel substrate depending on the solvent environment and produces a change in the fluorescence color and intensity as a sensory signal. The devised sensor device, which is fabricated with simple drop-casting of the DPP derivative solutions onto a silica gel substrate, exhibited a completely reversible fluorescence signal change with large fluorescence signal contrast, which allows selective solvent detection by simple optical observation with the naked eye under UV light. Superior selectivity of the alcohol and water sensor system, which can clearly distinguish among ethanol, methanol, ethylene glycol, and water, is demonstrated. PMID- 27668521 TI - Spectroscopic Investigation of Interfacial Interaction of Manganese Oxide with Triclosan, Aniline, and Phenol. AB - We investigated the reaction of manganese oxide [MnOx(s)] with phenol, aniline, and triclosan in batch experiments using X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and aqueous chemistry measurements. Analyses of XPS high resolution spectra suggest that the Mn(III) content increased 8-10% and the content of Mn(II) increased 12-15% in the surface of reacted MnOx(s) compared to the control, indicating that the oxidation of organic compounds causes the reduction of MnOx(s). Fitting of C 1s XPS spectra suggests an increase in the number of aromatic and aliphatic bonds for MnOx(s) reacted with organic compounds. The presence of 2.7% Cl in the MnOx(s) surface after reaction with triclosan was detected by XPS survey scans, while no Cl was detected in MnOx phenol, MnOx-aniline, and MnOx-control. Raman spectra confirm the increased intensity of carbon features in MnOx(s) samples that reacted with organic compounds compared to unreacted MnOx(s). These spectroscopy results indicate that phenol, aniline, triclosan, and related byproducts are associated with the surface of MnOx(s)-reacted samples. The results from this research contribute to a better understanding of interactions between MnOx(s) and organic compounds that are relevant to natural and engineered environments. PMID- 27668522 TI - Quinazolinone azolyl ethanols: potential lead antimicrobial agents with dual action modes targeting methicillin-resistant Staphylococcus aureus DNA. AB - AIM: Due to bacterial drug resistance, a new series of quinazolinone azolyl ethanols were synthesized and evaluated. RESULTS: In vitro antibacterial assay showed that triazolyl ethanol quinazolinone 3a was the most active compound, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimal inhibitory concentration value of 8 ug/ml, which was superior to chloromycin and comparable to norfloxacin. Molecular docking study displayed that compound 3a could interact with MRSA DNA by the formation of hydrogen bonds. Further interactions of quinazolinone 3a with MRSA DNA suggested that it could intercalate into MRSA DNA to form 3a-DNA complex. DNA cleavage properties of 3a Cu2+ and 3a-Zn2+ complexes were confirmed by agarose gel electrophoresis experiments. CONCLUSION: Compound 3a should be a potential lead antibacterial molecule with dual action modes. PMID- 27668523 TI - Associations Between Patient Characteristics and the Amount of Arthritis Medication Information Patients Receive. AB - Little is known about factors associated with the receipt of medication information among arthritis patients. This study explores information source receipt and associations between demographic and clinical/patient characteristics and the amount of arthritis medication information patients receive. Adult patients with osteoarthritis (OA) or rheumatoid arthritis (RA; n = 328) completed an online cross-sectional survey. Patients reported demographic and clinical/patient characteristics and the amount of arthritis medication information received from 15 information sources. Bivariate and multivariate linear regression analyses were used to investigate whether those characteristics were associated with the amount of medication information patients received. Arthritis patients received the most information from health professionals, followed by printed materials, media sources, and interpersonal sources. Greater receipt of information was associated with greater medication adherence, taking more medications, greater medication-taking concerns, more satisfaction with doctor medication-related support, and Black compared to White race. RA patients reported receiving more information compared to OA patients, and differences were found between RA patients and OA patients in characteristics associated with more information receipt. In conclusion, arthritis patients received the most medication information from professional sources, and both positive (e.g., greater satisfaction with doctor support) and negative (e.g., more medication taking concerns) characteristics were associated with receiving more medication information. PMID- 27668524 TI - Smoking Prevalence and Its Clinical Correlations in Patients with Narcolepsy cataplexy. AB - Narcolepsy-cataplexy (NC) is a chronic neurological disease with suggested autoimmune etiopathogenesis. Nicotine stimulates central nervous system and smoking increases the risk of autoimmune diseases. Assessment of smoking habits and its correlation to clinical parameters among 87 adult NC patients (38 male, 49 female) included night polysomnography and multiple sleep latency test. In our sample, 43.7% NC patients were regular smokers, and 19.5% former smokers compared to 22.2%, and 12.6%, respectively, in the general population. Patients started to smoke in the mean age of 20.0 (SD +/-6.0) years. 72.2% of NC smokers started to smoke before the onset of NC and the mean of the delay between smoking onset and NC onset was 9.1 (+/-5.8) years. We found a direct correlation between smoking duration and the number of awakenings, duration of N1 sleep, REM sleep latency, and apnoea/hypopnoea index (AHI), and, on the contrary, indirect correlation between smoking duration and N3 sleep duration, showing that smoking duration consistently correlates with sleep macrostructure. Smoking is highly prevalent in NC and has relationship with clinical features of NC. PMID- 27668525 TI - CCL5 rs2107538 Polymorphism Increased the Risk of Tuberculosis in a Sample of Iranian Population. AB - Cysteine-cysteine chemokine ligand 5 (CCL5) with immunoregulatory and inflammatory activities has an important role in granuloma formations that activates and stimulates T-cells and macrophages. Cysteine-cysteine chemokine receptor 5 (CCR5) is a chemokine receptor, which is important for migration of immune cells to site of infection. In the present study we investigated the possible association between CCL5 -403G/A (rs2107538), CCL5 -28C/G (rs2280788) and CCR5 Delta32 polymorphisms and pulmonary tuberculosis (PTB) in an Iranian population. This case-control study was performed on 160 patients with pulmonary tuberculosis and 160 unrelated healthy subjects. The CCL5 -403G/A, CCL5 -28C/G and CCR5 Delta32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR), tetra amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) and PCR, respectively. Our results showed that GA as well as GA+AA genotypes of CCL5 -403G/A (rs2107538) increased the risk of PTB in comparison with GG genotype (OR=1.70, 95% CI=1.03-2.81, P=0.038 and OR=1.64, 95% CI=1.00-2.68, P=0.049, respectively). No significant association was found between CCL5 -28C/G as well as CCR5 Delta32 polymorphism and PTB risk. In conclusion, our findings proposed that CCL5 -403G>A polymorphism may be a risk factor for susceptibility to PTB in our population. Larger sample sizes with different ethnicities are required to validate our findings. PMID- 27668526 TI - The Response of C19 Delta5-steroids to ACTH Stimulation and Hypoglycemia in Insulin Tolerance Test for Adrenal Insufficiency. AB - Studies on the time course of ACTH- or insulin-induced hypoglycemia stimulating adrenal androgens are usually limited to dehydroepiandrosterone and/or its sulphate. Our data on dehydroepiandrosterone (DHEA) and its hydroxylated metabolites clearly show that measurements of DHEA and its sulphate (DHEAS) are valuable markers of the integrity of the HPA (hypothalamus-pituitary-adrenal) axis. Assessments of HPA function should rely on measurements of baseline and/or stimulated serum cortisol concentrations, and C19 Delta5-steroids may provide additional information. The art of stimulation of 7- and 16-hydroxylated metabolites of DHEA can help our understanding of the formation sequence of these compounds. PMID- 27668527 TI - The Effect of Infliximab on Intestinal Anastomosis Healing in Rats. AB - Intestinal anastomosis healing is a complex physiological process in which many local and systemic factors play a role. One of the significant cytokines in this process is TNF-alpha. Infliximab is a chimeric monoclonal antibody which binds to TNF-alpha with high affinity. Although this agent is used in ulcerative colitis and Crohn's disease, intestinal surgery may be required in these patients. In this study it was aimed to determine whether or not there was any negative effect of preoperative single dose infliximab treatment on intestinal anastomosis healing. Two groups of 10 rats were formed. One of these groups was administered with a single dose of infliximab 8 mg/kg as a 20-minute intravenous infusion from the femoral vein. Four days after the infusion, a full layer incision was made to the colon and anastomosis was applied to all the rats. At 7 days after anastomosis, the subjects were sacrificed. The anastomosis segment was removed and the bursting pressure was measured. Tissue samples were taken from this segment for hydroxyproline concentration and histopathological examination. A blood sample was taken to measure TNF-alpha values. No statistically significant difference was determined between the groups in terms of bursting pressure, tissue hydroxyproline concentration or histopathological scoring. A single dose of 8 mg/kg infliximab administered 4 days preoperatively was not found to have any negative effect on intestinal anastomosis healing in rats. PMID- 27668528 TI - Thoracic Outlet Syndrome: A Significant Family Genetic Phenotypic Presentation. AB - We report on a very rare case of diagnosis and successful surgical treatment of three young family members with a four-fold presentation of thoracic outlet syndrome. In the relevant family case, we are considering and discussing the population incidence, a possible HOX genes disorder, and a significant phenotypic presentation. PMID- 27668529 TI - IgG4-related Diseases - A Rare Polycystic Form of Ormond's Disease. AB - Currently, Ormond's disease is classified among IgG4-associated diseases. Its clinical manifestation varies and is characterized by the presence of fibrous retroperitoneal tissue that often affects the ureters or abdominal aorta and iliac arteries. We present a unique case of the polycystic form of Ormond's disease, imitating tumour in the retroperitoneal space. At the time of diagnosis, the disease was not metabolically active and did not require immunosuppressive therapy. The polycystic mass was removed surgically. There has been no exacerbation of the disease during the last 12 months. PMID- 27668530 TI - Bone Metabolism of the Patient with a Malignant Melanoma during the Entry Examination and the Check-up of Whole-body Bone Scintigraphy. AB - Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (beta-CrossLaps, beta-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, beta-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease. PMID- 27668531 TI - Trichotillomania and co-occurring anxiety. AB - BACKGROUND: Trichotillomania appears to be a fairly common disorder, with high rates of co-occurring anxiety disorders. Many individuals with trichotillomania also report that pulling worsens during periods of increased anxiety. Even with these clinical links to anxiety, little research has explored whether trichotillomania with co-occurring anxiety is a meaningful subtype. METHODS: One hundred sixty-five adults with trichotillomania were examined on a variety of clinical measures including symptom severity, functioning, and comorbidity. Participants also underwent cognitive testing assessing motor inhibition and cognitive flexibility. Clinical features and cognitive functioning were compared between those with current co-occurring anxiety disorders (i.e. social anxiety, generalized anxiety disorder, panic disorder, and anxiety disorder NOS) (n=38) and those with no anxiety disorder (n=127). RESULTS: Participants with trichotillomania and co-occurring anxiety reported significantly worse hair pulling symptoms, were more likely to have co-occurring depression, and were more likely to have a first-degree relative with obsessive compulsive disorder. Those with anxiety disorders also exhibited significantly worse motor inhibitory performance on a task of motor inhibition (stop-signal task). CONCLUSIONS: This study suggests that anxiety disorders affect the clinical presentation of hair pulling behavior. Further research is needed to validate our findings and to consider whether treatments should be specially tailored differently for adults with trichotillomania who have co-occurring anxiety disorders, or more pronounced cognitive impairment. PMID- 27668532 TI - Anti-proliferation effects, efficacy of cyasterone in vitro and in vivo and its mechanism. AB - Cyasterone was demonstrated potential inhibition effect in mouse skin carcinoma cells in published report. However, the molecular mechanisms of the cyasterone on cells remain unknown. Herein, we investigated the effects of cyasterone-induced apoptosis in A549 and MGC823 cells in vitro. MTT assay showed that cyasterone caused a significantly decreasing of the proliferation of A549 and MGC823 cells in a time-and dose-dependent manner with IC50 values of 38.50+/-3.73MUg/mL on A549 cells and 32.96+/-1.24MUg/mL on MGC823 cells at 48h, respectively. Hoechst staining and TUNEL staining results indicated the quintessential apoptosis features in immunofluorescence image. Apoptosis and cell cycle were determined by flow cytometry. Cyasterone treatment triggered inhibition of epidermal growth factor receptor- phosphatidylinositol 3 kinase/protein kinase B (EGFR-AKT) signaling pathways and activation of P38 pathways. Furthermore, cyasterone inhibited MGC823 cells xenografted tumor growth in vivo with few changes in body weights. In conclusion, our findings provide the evidence that cyasterone inhibits growth of A549 and MGC823 cells, via regulating EGFR signaling pathway. Our results indicated that cyasterone, a natural EGFR inhibitor, maybe a promising anti-cancer agent. PMID- 27668533 TI - Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis. AB - Green tea polyphenolic catechins have been shown to prevent various types of diseases such as pulmonary hypertension (PAH), cancer and cardiac and neurological disorders. Matrix metalloproteinases (MMPs) play an important role in the development of PAH. The present study demonstrated that among the four green tea catechins (EGCG, ECG, EC and EGC), EGCG and ECG inhibit pro-/active MMP 9 activities in pulmonary artery smooth muscle cell culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-9 with the green tea catechins by computational methods. In silico molecular docking analysis revealed a strong interaction between pro-/active MMP-9 and EGCG/ECG, and galloyl group appears to be responsible for this enhanced interaction. The molecular docking studies corroborate our experimental observation that EGCG and ECG are mainly active in preventing both the proMMP-9 and MMP-9 activities. PMID- 27668534 TI - Effects of relaxin on cardiac fibrosis, apoptosis, and tachyarrhythmia in rats with myocardial infarction. AB - Relaxin is safe and efficient to use for treating acute heart failure. However, the electrophysiological and arrhythmogenic effects of relaxin in an experimental healing infarction model remain unknown. In this study, a rat model with myocardial infarction (MI) received relaxin (0.5mg/kg per day) or vehicle (sodium acetate) infusion via implantable mini-pumps for 2 weeks. Thereafter, hemodynamic measurement, electrophysiological study, histological examination, and immunofluorescence labeling were performed. Relaxin treatment significantly attenuated tachyarrhythmia inducibility and cardiac dysfunction in healing infarcted heart. Epicardial monophasic action potentials showed that relaxin significantly reduced the dispersion of action potential duration in postinfarcted hearts. Histological study revealed that relaxin significantly reduced myocardial apoptosis and cardiac fibrotic collagen deposition. Western blot revealed that relaxin treatment significantly suppressed the protein expression levels of TGFbeta1, alpha-SMA, and type I collagen. Furthermore, abnormal alterations of Connexin 43, including reduction and lateralization, were significantly attenuated by relaxin treatment at the infarcted border zone. This study provides strong evidence that continuous relaxin intervention ameliorates cardiac fibrosis and apoptosis, attenuates remodeling of gap junction and focal heterogeneity of repolarization, and reduces vulnerability to tachyarrhythmias. PMID- 27668535 TI - Potential blood clotting factors and anticoagulants. AB - Hemostasis initiates a wound healing process and stops bleeding of blood within a damaged tissue, an important process in human and animal systems. However, this process needs to revert temporarily during surgery and analyze the clotting mechanism. In the past decade, heparin has been used widely as an anticoagulant in surgery to prevent unwanted blood clotting as it is not expensive, not difficult to control, lack of suitable replacement as well as less harmful to the human. However, heparin has several disadvantages, which include thrombocytopenia and non-specific plasma binding. Moreover, using heparin it may lead dysfunction and platelet aggregation. In this overview, potential clotting factors and anticoagulants are reviewed and special focus was given to get more insights. PMID- 27668536 TI - Is ciprofloxacin safe in patients with solitary kidney and upper urinary tract infection? AB - The solitary kidney (SK) undergoes adaptive phenomena of hyperfunction and hyperfiltration. These secondary adaptive phenomena can make it more vulnerable to potentially nephrotoxic therapies. Adverse reactions of the kidneys to ciprofloxacin are rare, but sometimes severe. Therefore, our study sought to assess the reactions to ciprofloxacin of patients with solitary kidney (SK) and urinary tract infection (UTI) by means of urinary biomarkers. We studied 19 patients with SK and urinary tract infection (UTI) who had been administered a 7 day treatment with intravenous ciprofloxacin. Urinary N-acetyl-beta-d glucosaminidase, alpha 1-microglobulin, and estimated glomerular filtration rate (eGFR) of these patients were measured at the initiation and at the end of treatment. In 47.37% patients NAG diminished under ciprofloxacin treatment. This observation has the significance of favourable evolution of the tubulointerstitial lesions caused by UTI and lack of nephrotoxic effects; 52.63% cases presented an increase of urinary NAG, a fact that suggests a nephrotoxic effect of ciprofloxacin. The evolution of urinary alpha 1-microglobulin was similar to that one of urinary NAG. Only one of three cases with chronic kidney disease (CKD) stage 5 presented acute kidney injury, associated with increase in the tubular markers. In spite of the high variability of the urinary biomarkers, UTI evolved favourably in these cases; eGFR increased in 16 out of 19 patients, a fact which is indicative of a good outcome of renal function, even in patients with elevated levels of the tubular damage biomarkers. This observation supports the hypothesis that eGFR may be dissociated from the biomarkers which assess tubular injury. In SK patients the occurrence of AKI is not frequent, although the urinary biomarkers rise in some patients treated with ciprofloxacin. This is related not only to the nephrotoxic effect of the drug, but probably to the association of other factors (allergy, individual susceptibility). In SK patients, renal tubular biomarkers, especially NAG, allow monitoring of tubular injury and impose caution in prescribing ciprofloxacin treatment, mainly to patients at risk. Ciprofloxacin is relatively safe regarding its nephrotoxicity, while caution is required in vulnerable patients. PMID- 27668537 TI - A recombinant protein TmSm(T34A) can inhibit proliferation and proapoptosis to breast cancer stem cells(BCSCs) by down-regulating the expression of Cyclin D1. AB - Cancer stem cells (CSCs), a small fraction of cancer cells lines proved with stem cell characteristics, were regarded as "bad seeds" related to recurrence, metastasis and chemotherapy resistance of breast carcinoma in recent years. So inhibiting the growth or inducing the differentiation and apoptosis of CSCs were considered as one of the effective pathways to fight against breast cancer. Based on the recombinant protein TmSm(T34A) that was designed and prepared in our previous experiments for targeting survivin, an inhibitor of apoptosis protein(IAP), in this study, we explored the effects of TmSm(T34A) on BCSCs obtained by enriching in serum-free suspension, sorting and characterizing of MCF 7/ADM. The results showed that TmSm(T34A) could not only inhibit the proliferation and growth of BCSCs by decreasing CD44+CD24- proportion and down regulating the expression of Cyclin D1 significantly, but also induce BCSCs apoptosis evidently. Furthermore, in BCSCs xenograft nude mice administrated TmSm(T34A), the tumor growth was slower than that of the control obviously. Thus it can be seen TmSm(T34A) would be a promising potential protein for treatment of breast cancer by effecting on BCSCs. PMID- 27668538 TI - Neuromodulatory effects of Calyptranthes grandifolia extracts against 6 hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. AB - Alzheimer's and Parkinson's diseases are neurodegenerative disorders characterized by progressive neuronal dysfunction. Previous studies revealed that some natural products have neuroprotective properties, including species of the Myrtaceae family. However, the neuromodulatory potential of Calyptranthes grandifolia is not clear. In the present study, we examined the ability of the ethanol and hexane leaf extracts of C. grandifolia to prevent 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. Initially, we investigated the potential of the extracts to inhibit the neurodegenerative-related enzymes c-Jun N-terminal kinase 3 (JNK3) and acetylcholinesterase (AChE). In addition, SH-SY5Y cell viability was assessed by MTT assay after 100MUM 6-OHDA-induced cell damage. In order to verify the possible effects of both extracts on 6-OHDA-induced cell death, hydrogen peroxide generation, mitochondrial potential and caspases-3 activity were assessed. Our findings revealed that ethanol extract exhibited inhibitory activity against JNK3 and AChE. In addition, when co-treating SH-SY5Y cells with 6-OHDA and the extracts, oxidative stress was inhibited by both extracts through a decrease of mitochondrial depolarization and caspases-3 activity. In summary, ethanol and hexane extracts of C. grandifolia have some suppressive property against neurotoxicity induced by 6-OHDA. PMID- 27668539 TI - Neuroprotective effects of Caralluma tuberculata on ameliorating cognitive impairment in a d-galactose-induced mouse model. AB - Cognitive deficiency and oxidative stress have been well documented in aging disorders including Alzheimer's disease. The aim of this study was to investigate the therapeutic efficacy of Caralluma tuberculata methanolic extract (CTME) on cognitive impairment in mice induced with d-galactose. In this study we assessed the therapeutic efficacy of CTME on cognitive impairment in mice induced with d galactose by conduction of behavioral and cognitive performance tests. In order to explore the possible role of CTME against d-galactose-induced oxidative damages, various biochemical indicators were assessed. Chronic administration of d-galactose (150mg/kgd, s.c.) for 7 weeks significantly impaired cognitive performance (in step-through passive, active avoidance test, Hole-Board test, Novel object recognition task and Morris water maze) and oxidative defense as compared to the control group. The results revealed that CTME treatment for two weeks (100, 200 and 300mg/kg p.o) significantly ameliorated cognitive performance and oxidative defense. All groups of CTME enhanced the learning and memory ability in step-through passive, active avoidance test, Hole-Board test Novel object recognition task and Morris water maze. Furthermore, high and middle level of CTME (300 and 200mg/kg p.o) significantly increased Total antioxidative capacity (T-AOC), Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, neprilysin (NEP), and beta-site AbetaPP cleaving enzyme 1 (BACE1) expression while Nitric Oxide (NO), Nitric Oxide Synthase (NOS) activity and Malondialdehyde (MDA) concentration, and the level of Abeta1-42 and presenilin 1 (PS1) were decreased. The present study showed that CTME have a significant relieving effect on learning, memory and spontaneous activities in d-galactose induced mice model, and ameliorates cognitive impairment and biochemical dysfunction in mice. PMID- 27668540 TI - Small-molecule GSK-3 inhibitor rescued apoptosis and neurodegeneration in anesthetics-injured dorsal root ganglion neurons. AB - BACKGROUND: Application of general anesthetics may induce neurotoxicity in dorsal root ganglia (DRG) neurons. In this study, we examined the possible protective mechanism and associated signaling pathways of small-molecule glycogen synthase kinase-3 (GSK-3) inhibitor, SB216763, in bupivacaine-injured mouse DRG neurons in vitro. METHODS: In vitro DRG explant of 6-week old mice was treated with 5mM bupivacaine to induce neurotoxicity. The explants were also pre-treated with SB216763 for 72h. Neural protection of SB216763 on bupivacaine-injured DRG neurons was investigated by TUNEL assay, neurite outgrowth assay and western blot assay, respectively. Possible downstream gene of GSK-3 signaling pathway, protein kinase C (PKC) was knocked down by siRNA in DRG explant. Its function in regulating GSK-3 inhibition induced DRG neural protection was also examined by TUNEL, neurite outgrowth and western blot assays. RESULTS: Pre-treatment of SB216763 significantly ameliorated bupivacaine induced apoptosis and neurite loss in DRG neurons. Western blot showed that, in addition to the decrease of phosphorylated-GSK-3 alpha/beta protein, SB216763 increased PKC and decreased caspase-3 (Casp-3) in bupivacaine-injured DRG neurons. SiRNA-mediated PKC knockdown was able to reverse the neural protection of SB216763 in bupivacaine injured DRG neurons. Western blot showed that PKC knockdown increased phosphorylated-GSK-3 alpha/beta and Casp-3 protein in DRG neurons, confirming that PKC was directly involved in GSK-3-inhibition induced neural protection in DRG. CONCLUSIONS: GSK-3 inhibitor SB216763, through PKC, is effective in protecting anesthetics-induced neurotoxicity in DRG. PMID- 27668541 TI - Evaluation of the antiproliferative activity of 2-amino thiophene derivatives against human cancer cells lines. AB - In spite of great progress in understanding cancer biology, current therapeutic procedures remain unsatisfactory. Chemotherapy is often followed by secondary effects with cellular toxicity negatively affecting the results. The discovery and development of new safe and efficient antitumor agents is necessary. Derivatives of 2-amino thiophene have been a topic of constant investigation due to their versatile synthetic applicability and broad spectrum of biological applications; among which are antifungal and antiproliferative activity shown in prior studies of our group. In the current study, compounds 6CN09, 6CN10, 6CN12, 6CN14, 7CN09 and 7CN11 were analyzed as to antiproliferative effect in human cells of cervical adenocarcinoma (HeLa), human pancreatic adenocarcinoma (PANC-1) and mice fibroblasts (3T3), which were exposed to the compounds in concentrations of 5, 10, 25 and 50MUM during 24 and 48h. They were submitted to MTT assay. In order to elucidate the action mechanism of antitumor thiophene derivatives flow cytometry was performed to evaluate cell death and cell cycle analysis. The results showed that thiophene derivatives demonstrated great antiproliferative potential in the HeLa and PANC-1 cell lines when compared with the control, and the percentage of cell proliferation inhibition approximated or was higher than the standard drug used; doxorubicin (Dox). In highlight were the derivatives 6CN14 and 7CN09 that showed greater efficiency in the antiproliferative evaluation. Further, all compounds had a protective effect on the non-tumor 3T3 cell line. The flow cytometry analysis showed few cells in apoptosis in both the HeLa and PANC-1 lines, although the compounds interfered with the progression of the cell cycle, and avoided cell growth and multiplication in the HeLa tumor line. These thiophene derivatives demonstrated cytostatic and antiproliferative effects and may be considered as promising molecular candidates for anticancer drugs. PMID- 27668542 TI - Evaluation of anti-diabetic and anti-tumoral activities of bioactive compounds from Phoenix dactylifera L's leaf: In vitro and in vivo approach. AB - Among various chronic disorders, cancer and diabetes mellitus are the most common disorders. This study was designed to evaluate the effectiveness of hydroalcoholic extract of Phoenix dactylifera L. leaves (HEPdL) in animal models of type II diabetes in vitro/in vivo and in a human melanoma-derived cell line (IGR-39). A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was also performed to determine the amount of phenolic and flavonoid compounds in this plant. The physicochemical results by LC-MS/MS analysis of HEPdL showed the presence of 10 phenolic compounds. The in vitro study showed that the extract exhibited a more specific and potent inhibitor of alpha-glucosidase than alpha amylase with an IC50 value of 20+/-1MUg/mL and 30+/-0.8MUg/mL, respectively. More importantly, the in vivo study of the postprandial hyperglycemia activity with (20mg/kg) of HEPdL showed a decrease in plasma glucose levels after 60min in resemblance to the glucor (acarbose) (50mg/kg) effect. The oral administration of HEPdL (20mg/kg) in alloxan-induced diabetic mices for 28days showed a more significant anti-diabetic activity than that of the drug (50mg/kg). Moreover, cytotoxicity effects of HEPdL in IGR-39 cancer cell lines were tested by MTT assay. This extract was effective in inhibiting cancer cells growth (IGR-39) at dose 35 and 75MUg/mL. These results confirm ethnopharmacological significance of the plant and could be taken further for the development of an effective pharmaceutical drug against diabetes and cancer. PMID- 27668543 TI - What Patient Characteristics Influence Nurses' Assessment of Health Literacy? AB - Overestimation of patients' health literacy skills is common among nurses and physicians. At Vanderbilt University Hospital, nurses routinely ask patients the 3 Brief Health Literacy Screen (BHLS) questions. Data from 2 studies that recruited patients at Vanderbilt University Hospital-the Health Literacy Screening (HEALS) study and the Vanderbilt Inpatient Cohort Study (VICS)-were analyzed to compare the BHLS score recorded by nurses during clinical care with the score recorded by trained research assistants during the same hospitalization. Logistic regression models determined which patient characteristics were associated with nurses documenting higher health literacy scores than research assistants. Overall, the majority (60%) of health literacy scores were accurate, though nurses recorded meaningfully higher health literacy scores in 28.4% of HEALS patients and 35.6% of VICS patients. In the HEALS cohort, patients who were male and had less education were more likely to have higher health literacy scores recorded by nurses (odds ratio [OR] = 1.93, 95% confidence interval [CI] [1.24, 3.00]; and OR = 0.80, 95% CI [0.74, 0.88], respectively). In the VICS cohort, patients who were older, were male, and had less education were more likely to have higher health literacy scores recorded by nurses (OR = 1.01, 95% CI [1.003, 1.02]; OR = 1.49, 95% CI [1.20, 1.84]; and OR = 0.87, 95% CI [0.83, 0.90], respectively). These findings suggest that health literacy scores recorded by nurses for male patients and patients with less education could be overestimated. Thus, health care professionals should be aware of this tendency and should verify the results of routine health literacy screening tests, especially in certain patient groups. PMID- 27668544 TI - Appendectomy in Pregnancy: Appraisal of the Minimally Invasive Approach. AB - BACKGROUND: The optimal surgical approach to acute appendicitis in pregnancy remains controversial. Our aim was to compare perioperative and obstetric outcomes associated with laparoscopic and open appendectomy in a large contemporary cohort of pregnant women. METHODS: Retrospective review of all women who underwent appendectomy during pregnancy in a single hospital during 2000 2014. RESULTS: Ninety-two patients met the study criteria. Fifty (54%) underwent laparoscopic appendectomy and 42 (46%) open appendectomy. The laparoscopy group had a lower median gestational age at surgery (16 weeks versus 24 weeks, P < .001), a shorter median hospital stay (5 days versus 3 days, P < .001), and a lower rate of postoperative complications (8% versus 24%, P = .04). There were no significant between-group differences in the rates of gestational age at delivery, Apgar scores, preterm delivery, and fetal loss. CONCLUSIONS: Laparoscopic appendectomy during pregnancy is safe and associated with better surgical outcomes than open appendectomy, with no difference in obstetric outcomes. PMID- 27668545 TI - Verification of Frequency in Species of Nontuberculous Mycobacteria in Kermanshah Drinking Water Supplies Using the PCR-Sequencing Method. AB - BACKGROUND: Nontuberculous mycobacteria are habitants of environment, especially in aquatic systems. Some of them cause problems in immunodeficient patients. Over the last decade, 16S rRNA gene sequencing was established in 45 novel species of nontuberculous mycobacteria. Experiences revealed that this method underestimates the diversity, but does not distinguish between some of mycobacterium subsp. To recognize emerging rapidly growing mycobacteria and identify their subsp, rpoB gene sequencing has been developed. OBJECTIVES: To better understand the transmission of nontuberculous mycobacterial species from drinking water and preventing the spread of illness with these bacteria, the aim of this study was to detect the presence of bacteria by PCR-sequencing techniques. MATERIALS AND METHODS: Drinking water samples were collected from different areas of Kermanshah city in west of IRAN. After decontamination with cetylpyridinium chloride, samples were filtered with 0.45-micron filters, the filter transferred directly on growth medium waiting to appear in colonies, then DNA extraction and PCR were performed, and products were sent to sequencing. RESULTS: We found 35/110 (32%) nontuberculous mycobacterial species in drinking water samples, isolates included Mycobacterium goodii, Mycobacterium aurum, and Mycobacterium gastri with the most abundance (11.5%), followed by Mycobacterium smegmatis, Mycobacterium porcinum, Mycobacterium peregrinum, Mycobacterium mucogenicum, and Mycobacterium chelonae (8%). CONCLUSIONS: In this study, we recognized the evidence of contamination by nontuberculous mycobacteria in corroded water pipes. As a result of the high prevalence of these bacteria in drinking water in Kermanshah, this is important evidence of transmission through drinking water. This finding can also help public health policy makers control these isolates in drinking water supplies in Kermanshah. PMID- 27668547 TI - Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain. AB - Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock (PER1) and clock controlled (vasopressin) proteins. To determine if these SCN changes are due to the metabolic or timing cues of the restricted feeding, mice were challenged with an ultradian 6-meals schedule (1 food access every 4 h) to abolish the daily periodicity of feeding. Mice fed with ultradian feeding that lost <10% body mass (i.e. isocaloric) displayed 1.5-h phase-advance of body temperature rhythm, but remained mostly nocturnal, together with up-regulated vasopressin and down regulated PER1 and PER2 levels in the SCN. Hepatic expression of clock genes (Per2, Rev-erbalpha, and Clock) and Fgf21 was, respectively, phase-advanced and up-regulated by ultradian feeding. Mice fed with ultradian feeding that lost >10% body mass (i.e. hypocaloric) became more diurnal, hypothermic in late night, and displayed larger (3.5 h) advance of body temperature rhythm, more reduced PER1 expression in the SCN, and further modified gene expression in the liver (e.g. larger phase-advance of Per2 and up-regulated levels of Pgc-1alpha). While glucose rhythmicity was lost under ultradian feeding, the phase of daily rhythms in liver glycogen and plasma corticosterone (albeit increased in amplitude) remained unchanged. In conclusion, the additional impact of hypocaloric conditions on the SCN are mainly due to the metabolic and not the timing effects of restricted daytime feeding. PMID- 27668546 TI - An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia. AB - BACKGROUND: Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose. OBJECTIVE: To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes. METHODS: A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration. RESULTS: There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size. CONCLUSIONS: Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing. PMID- 27668548 TI - Development of a measure to evaluate gains among spanish dementia caregivers: The gains associated with caregiving (GAC) scale. AB - BACKGROUND: The study is aimed at developing a new measure devised to evaluate gains associated with caregiving for a person with dementia. METHODS: We conducted two studies with Spanish informal caregivers. In Study 1 a total of 152 participants responded to a preliminary set of 62 items referred to gains related with caregiving. After exploring their psychometric properties, we studied its factor structure, concurrent validity, and internal consistency reliability by means of, respectively, an exploratory factor analysis (EFA), its correlation with the similar measures, and Cronbach's alpha coefficients. In Study 2 we undertook a confirmatory factor analysis (CFA) to obtain further evidence regarding the scale dimensionality and we studied its construct validity by calculating its correlations with the Zarit Burden Interview (ZBI), the Geriatric Depression Scale - Short Form (GDS-SF), and the Satisfaction With Life Scale (SWLS). RESULTS: The final version of the Gains Associated with Caregiving (GAC) scale comprised 22 items, all of which seemed to belong to the same factor according to both the EFA and the CFA. The correlation between the GAC scale and similar measures was statistically significant and strong, and the Cronbach's alpha coefficient was 0.95. Statistically significant correlations in the expected direction were found between the GAC and the ZBI, the GDS-SF, and the SWLS. CONCLUSIONS: The high internal consistency of the GAC scale, and its adequate concurrent and construct validity suggest that it is a suitable instrument for evaluating gains among Spanish informal dementia caregivers. PMID- 27668549 TI - Salivary estradiol as a surrogate marker for serum estradiol in assisted reproduction treatment. AB - INTRODUCTION: Controlled ovarian hyper-stimulation for in vitro fertilization or intra cytoplasmatic sperm injection necessitates close monitoring using ultrasound and estradiol measurements. Monitoring is also important to prevent or limit the severity of ovarian hyper stimulation syndrome, an iatrogenic and potentially life-threatening complication. Self-operated endovaginal telemonitoring has been shown to offer an attractive and less costly alternative to classic consultation and saliva estradiol measurements could be a stress-free and practical alternative to serial blood determinations. Objectives were to evaluate whether saliva can be a surrogate marker for serum estradiol and its potential applicability in assisted reproduction treatment monitoring. MATERIAL AND METHODS: Serial blood and saliva samples were collected from 31 patients undergoing ovarian hyper-stimulation. All patients were followed-up using in house serial vaginal sonograms and immunoassay serum estradiol measurements. Afterwards estradiol was determined in saliva and serum by LC-MS/MS. For a subset equilibrium dialysis and measurement of free serum estradiol was performed. RESULTS: About 1% of estradiol is present in serum in its free, unbound, form. Salivary estradiol correlates well to both serum free estradiol and serum total estradiol (r=0.80). The concentration of salivary estradiol corresponds to the unbound concentration in serum. The dynamics observed in serum monitoring during treatment are closely mimicked in saliva. ROC analysis on the current limited dataset suggested a saliva cut-off of 22pg/mL (81pmol/L) could help predict risk for OHSS. CONCLUSIONS: Salivary E2 can be considered a surrogate marker for free serum estradiol and total serum estradiol in assisted reproduction treatment. Additionally there might be a role as a prediction marker for OHSS although this finding has to be validated in larger datasets. PMID- 27668550 TI - Analytical investigation of Mudejar polychrome on the carpentry in the Casa de Pilatos palace in Seville using non-destructive XRF and complementary techniques. AB - The pigments, execution technique and repainting used on the polychrome wood ceilings and doors in the Casa de Pilatos (Seville, Spain) were studied using portable X-ray fluorescence equipment. Cross-sections of small samples were also analysed by optical microscopy, SEM with EDX analysis, micro-Raman and micro infrared spectroscopy and X-ray diffraction. These carpentry works are magnificent examples of the Mudejar art made in Spain in the early 16th century. Portable X-ray fluorescence gave good information on the different components of the polychrome. The SEM-EDX study of the surfaces of small samples gave information on their components and also characterized the compounds that had been deposited or formed by environmental contamination or by the alteration of some pigments. The SEM-EDX study of cross-sections facilitated the characterization of all layers and pigments from the support to the most external layer. The following pigments were characterized: red (cinnabar/vermillion, lead oxide, iron oxides and orpiment/realgar), black (carbon black), white (white lead and titanium barium white), yellow-orange-red-brown (orpiment/realgar and iron oxides), green (chromium oxide), blue (indigo blue and ultramarine blue), and gilding (gold leaf on bole). False gold, bronze and brass were also found. The pigments were applied with the oil painting technique over a support layer that had been primed with animal glue. This support layer was gypsum in some cases and white lead in others. This study is essential to the polychrome conservation of the studied artwork, and it will help clarify uncertainties in the history and painting of Mudejar art. PMID- 27668552 TI - Management of traumatic blunt IVC injury. AB - INTRODUCTION: Injuries to the inferior vena cava (IVC) secondary to blunt trauma are rare and occurs in less than 1% of all blunt trauma patients. Mortality rates for IVC injuries reported in the literature range from 34% to 70%. Inferior vena cava (IVC) pseudoaneurysms resulting from these injuries are also rare clinical entities with an uncertain natural history due to limited follow-up information. CASE PRESENTATION: This case report describes a 23-year-old woman with traumatic IVC dissection resulting in pseudoaneurysms. It also details our treatment plan, with follow-up through radiographic resolution of the pseudoaneurysms. DISCUSSION: Due to rarity of these injuries, management of these injuries has not been subjected to major studies, but several case reports and small retrospective studies have demonstrated that management can be tailored to the hemodynamic status of the patient. Stable patients whose injuries have achieved local venous tamponade have been successfully treated without surgical intervention, while unstable patients require operative management. CONCLUSION: Of all incoming patients, IVC injuries are highly fatal with mortality rates between 70 and 90%. Management of these injuries should be tailored based on hemodynamic stability of such patients. PMID- 27668551 TI - Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders. AB - OBJECTIVE: A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. METHODS: Using a cross sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. RESULTS: There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. CONCLUSIONS: The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum. PMID- 27668553 TI - Aquaporin 4 Antibody in the Korean Patient with New-Onset Optic Neuritis. AB - PURPOSE: To evaluate the prevalence of aquaporin 4 antibody (AQP4-Ab) in new onset optic neuritis patients and investigate the characteristics of seropositive patients. METHODS: Thirty-six women and six men with new-onset isolated optic neuritis were included in this study between January 2013 and December 2014. AQP4 Ab was detected and all blood samples were obtained prior to treatment and within one week from attack. The patients were sub-grouped into either a seropositive group or a seronegative group according to AQP4-Ab. Differences in age, gender, initial visual acuity, and final visual acuity between groups were analyzed. RESULTS: Six (14.3%) of these patients (five women and one man) exhibited AQP4 Ab. There was no significant difference in mean age between study groups (positive group: 38.7 +/- 11.5 years, negative group: 42.3 +/- 14.7 years, P=0.548). Bilateral simultaneous involvement was more common in seropositive patients than in seronegative patients (occurred in two out of six seropositive patients and in one out of 36 seronegative patients, P = 0.007). With regards to poor visual outcome (worse than 1.0 LogMAR), seropositive patients exhibited more severe visual loss than seronegative patients. None of the seropositive patients exhibited myelitis symptoms during the follow-up period (mean follow-up period: 8 32 months). CONCLUSION: The prevalence of AQP4 antibody was often detected in new onset optic neuritis patients. In patients with bilateral involvement or poor initial visual acuity, the AQP4 antibody test should be considered. PMID- 27668554 TI - Pharmaceutical applications of affinity-ultrafiltration mass spectrometry: Recent advances and future prospects. AB - The immunoaffinity of protein with ligand is broadly involved in many bioanalytical methods. Affinity-ultrafiltration mass spectrometry (AUF-MS), a platform based on interaction of protein-ligand affinity, has been developed to fish out interesting molecules from complex matrixes. Here we reviewed the basics of AUF-MS and its recent applications to pharmaceutical field, i.e. target oriented discovery of lead compounds from combinatorial libraries and natural product extracts, and determination of free drug concentration in biosamples. Selected practical examples were highlighted to illustrate the advances of AUF-MS in pharmaceutical fields. The future prospects were also presented. PMID- 27668559 TI - The GRACE Checklist: A Validated Assessment Tool for High Quality Observational Studies of Comparative Effectiveness. AB - BACKGROUND: Recognizing the growing need for robust evidence about treatment effectiveness in real-world populations, the Good Research for Comparative Effectiveness (GRACE) guidelines have been developed for noninterventional studies of comparative effectiveness to determine which studies are sufficiently rigorous to be reliable enough for use in health technology assessments. OBJECTIVE: To evaluate which aspects of the GRACE Checklist contribute most strongly to recognition of quality. METHODS: We assembled 28 observational comparative effectiveness articles published from 2001 to 2010 that compared treatment effectiveness and/or safety of drugs, medical devices, and medical procedures. Twenty-two volunteers from academia, pharmaceutical companies, and government agencies applied the GRACE Checklist to those articles, providing 56 assessments. Ten senior academic and industry experts provided assessments of overall article quality for the purpose of decision support. We also rated each article based on the number of annual citations and impact factor of the journal in which the article was published. To identify checklist items that were most predictive of quality, classification and regression tree (CART) analysis, a binary, recursive, partitioning methodology, was used to create 3 decision trees, which compared the 56 article assessments with 3 external quality outcomes: (1) expert assessment of overall quality, (2) citation frequency, and (3) impact factor. A fourth tree looked at the composite outcome of all 3 quality indicators. RESULTS: The best predictors of quality included the following: use of concurrent comparators, limiting the study to new initiators of the study drug, equivalent measurement of outcomes in study groups, collecting data on most if not all known confounders or effect modifiers, accounting for immortal time bias in the analysis, and use of sensitivity analyses to test how much effect estimates depended on various assumptions. Only sensitivity analyses appeared consistently as a predictor of quality in all 4 trees. When a composite outcome of the 3 quality measures was used, the GRACE Checklist showed high sensitivity and specificity (71.43% and 80.95%, respectively). CONCLUSIONS: The GRACE Checklist stands out from other consensus-driven and expert guidance documents because of its extensive validation efforts. This most recent work shows that the checklist has strong sensitivity and specificity, increasing its utility as a screening tool to identify high-quality observational comparative effectiveness research worthy of in-depth review and applicability for decision support. DISCLOSURES: No outside funding supported this research. All authors are full time employees of Quintiles, which provides research and consulting services to the biopharmaceutical industry. The authors have no other disclosures to report. Two of the 3 CART trees were presented at the International Society of Pharmacepidemiology in 2015 ("Article Citations per Year" and "Journal Impact Factor"). The original validation study was published in the March 2014 issue of the Journal of Managed Care & Specialty Pharmacy. The checklist questions and scoring were included using a table that was originally published by this journal in 2014. Study concept and design were primarily contributed by Dreyer and Velentgas, along with Bryant. Bryant took the lead in data collection and analysis, along with Dreyer and Velentgas, and data interpretation was performed by Dreyer, Velentgas, and Bryant. The manuscript was written and revised primarily by Dreyer, along with Bryant and Velentgas. PMID- 27668560 TI - The Central Role of Physician Leadership for Driving Change in Value-Based Care Environments. AB - BACKGROUND: In 2013, it was reported that about 1 of every 3 U.S. adults has hypertension. Of these 70 million individuals, approximately 50% have their blood pressure under control. Achieving hypertension control, especially in at-risk populations, requires a multipronged approach that includes lifestyle modifications and pharmacological treatment. As provider groups, hospital systems, and integrated delivery networks optimize their care processes to promote population health activities in support of the accountable care organization (ACO) model of care, managing hypertension and other chronic diseases will be essential to their success. A critical aspect of managing populations in an ACO environment is optimization of care processes among providers to increase care efficiency and improve patient outcomes. PROGRAM DESCRIPTION: Launched in 2013, Measure Up/Pressure Down is a 3-year campaign developed by the American Medical Group Foundation (AMGF) to reduce the burden of high blood pressure. The goal of the campaign is for participating medical groups, health systems, and other organized systems of care to achieve hypertension control for 80% of their patients with high blood pressure by 2016, according to national standards. The role of physician leadership at Cornerstone Health Care (CHC) and Summit Medical Group (SMG) in facilitating organizational change to improve hypertension management through the implementation of the Measure Up/Pressure Down national hypertension campaign is examined. OBSERVATIONS: Using patient stratification via its electronic health record, SMG identified 16,000 patients with hypertension. The baseline percentage of hypertension control for this patient population was 66%. Within 7 months, SMG was able to meet the 80% goal set forth by the AMGF's Measure Up/Pressure Down campaign. CHC diagnosed 25,312 patients with hypertension. The baseline percentage of hypertension control for this subgroup of patients was 51.5% when the initiative was first implemented. To date, the organization has achieved 72% hypertension control for at-risk patients and continues work towards the 80% campaign goal. The implementation of the Measure Up/Pressure Down campaign by CHC and SMG provides some valuable lessons. To further explore important aspects of successfully implementing the Measure Up/Pressure Down campaign in real-world settings, 6 key themes were identified that drove quality improvement and may be helpful to other organizations that implement similar quality improvement initiatives: (1) transitioning to value-based payments, (2) creating an environment for success, (3) leveraging program champions, (4) sharing quality data, (5) promoting care team collaboration, and (6) leveraging health information technology. IMPLICATIONS: The strategies employed by SMG and CHC, such as leveraging data analysis to identify at-risk patients and comparing physician performance, as well as identifying leaders to institute change, can be replicated by an ACO or a managed care organization (MCO). An MCO can provide data analysis services, sparing the provider groups the analytic burden and helping the MCO build a more meaningful relationship with their providers. DISCLOSURES: No outside funding supported this project. The authors declare no conflicts of interest. The authors are members of the Working Group on Optimizing Medication Therapy in Value-Based Healthcare. Odgen is employed by Cornerstone Health Care; Brenner is employed by Summit Medical Group; and Penso is employed by American Medical Group Association. Lustig, Westrich, and Dubois are employed by the National Pharmaceutical Council, an industry-funded health policy research organization that is not involved in lobbying or advocacy. Study concept and design were contributed by Lustig, Penso, Westrich, and Dubois. Lustig, Ogden, Brenner, and Penso collected the data, and data interpretation was performed by all authors. The manuscript was written primarily by Lustig, along with the other authors, and revised by Lustig, Penso, Westrich, and Dubois, assisted by Ogden and Brenner. PMID- 27668561 TI - Quality Assessment of Medical Apps that Target Medication-Related Problems. AB - BACKGROUND: The advent of smartphones has enabled a plethora of medical apps for disease management. As of 2012, there are 40,000 health care-related mobile apps available in the market. Since most of these medical apps do not go through any stringent quality assessment, there is a risk of consumers being misinformed or misled by unreliable information. In this regard, apps that target medication related problems (MRPs) are not an exception. There is little information on what constitutes quality in apps that target MRPs and how good the existing apps are. OBJECTIVE: To develop a quality assessment tool for evaluating apps that target MRPs and assess the quality of such apps available in the major mobile app stores (iTunes and Google Play). METHODS: The top 100 free and paid apps in the medical categories of iTunes and Google Play stores (total of 400 apps) were screened for inclusion in the final analysis. English language apps that targeted MRPs were downloaded on test devices to evaluate their quality. Apps intended for clinicians, patients, or both were eligible for evaluation. The quality assessment tool consisted of 4 sections (appropriateness, reliability, usability, privacy), which determined the overall quality of the apps. Apps that fulfilled the inclusion criteria were classified based on the presence of any 1 or more of the 5 features considered important for apps targeting MRPs (monitoring, interaction checker, dose calculator, medication information, medication record). Descriptive statistics and Mann-Whitney tests were used for analysis. RESULTS: Final analysis was based on 59 apps that fulfilled the study inclusion criteria. Apps with interaction checker (66.9%) and monitoring features (54.8%) had the highest and lowest overall qualities. Paid apps generally scored higher for usability than free apps (P = 0.006) but lower for privacy (P = 0.003). Half of the interaction checker apps were unable to detect interactions with herbal medications. Blood pressure and heart rate monitoring apps had the highest overall quality scores (67.7%), while apps that monitored visual, hearing, and temperature changes scored the lowest (35.5%). CONCLUSIONS: A quality assessment tool for evaluating medical apps targeting MRPs has been developed. Clinicians can use this tool to guide their assessments of medical apps that are appropriate for use in the health care setting. Although potentially useful apps were identified, many apps were found to have deficiencies in quality, among which was poor reliability scores for most of the apps. Continued assessments of the quality of apps targeting MRPs are recommended to ensure their usefulness for clinicians and patients. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interests directly related to this study. Study concept and design were contributed by Loy and Yap. Loy collected the data and took the lead in data interpretation, along with Ali and Yap. The manuscript was primarily written by Loy, along with Yap, and revised primarily by Ali, along with Yap. PMID- 27668562 TI - Estimating Generic Drug Use with Electronic Health Records Data from a Health Care Delivery System: Implications for Quality Improvement and Research. AB - BACKGROUND: Generic drug use in the outpatient setting is typically measured with adjudicated pharmacy claims; however, not all delivery systems have access to these data for their clinical populations. OBJECTIVE: To develop an algorithm to estimate generic drug use in an outpatient setting using electronic health records (EHR) data. METHODS: Twenty-five therapeutic classes were chosen with the potential for low generic use that were prescribed to managed care beneficiaries in a health care system in Northern California. An algorithm was developed to estimate generic drug use based on medication names and dispense-as-written requests from electronic prescriptions, as well as information on generic availability at the time the prescriptions were written. The algorithm was used to quantify a generic utilization rate (GUR) across therapeutic classes and was validated by comparing the estimated GUR to the true GUR, using pharmacy claims corresponding to prescriptions in the same patient cohort. RESULTS: Among managed care beneficiaries, 104,859 prescriptions were identified for drugs in the therapeutic classes of interest with corresponding pharmacy claims. The algorithm estimated a GUR of 73.7% across 25 unique classes. The actual GUR based on pharmacy claims was 73.1%. Sensitivity (97%) and specificity (89%) of the algorithm were high, and total percentage of agreement was 95%. CONCLUSIONS: An algorithm that estimates generic drug use performed well in a population of managed care beneficiaries. Health care delivery systems may apply methods described in this article to quantify generic drug use in their ambulatory populations for quality improvement and research initiatives, particularly when pharmacy claims are unavailable. DISCLOSURES: This study was funded by a grant from the U.S. Food and Drug Administration in cooperative agreement with the Johns Hopkins School of Medicine and the Palo Alto Medical Foundation Research Institute (1U01FD005267-01). Romanelli has received research grant support from Pfizer and Janssen Scientific Affairs. Authors have no other conflicts to disclose. Romanelli and Segal contributed the study concept and design. Nimbal took the lead in data collection, assisted by Romanelli. All authors were involved with data interpretation and revision of the manuscript. The manuscript was written by Romanelli and Nimbal. PMID- 27668563 TI - Financial Hardship from Purchasing Medications for Senior Citizens Before and After the Medicare Modernization Act of 2003 and the Patient Protection and Affordable Care Act of 2010: Findings from 1998, 2001, and 2015. AB - BACKGROUND: The Medicare Modernization Act of 2003 (Medicare Part D) added prescription drug coverage for senior citizens aged 65 years and older and applied managed care approaches to contain costs. The Patient Protection and Affordable Care Act of 2010 (ACA) had the goals of expanding health care insurance coverage and slowing growth in health care expenditures. OBJECTIVES: To (a) describe the proportion of senior citizens who had prescription drug insurance coverage and the proportion who experienced financial hardship from purchasing medications in 2015, and (b) compare the findings with those collected in 1998 and 2001. METHODS: Data were obtained in 1998 and 2001 via surveys mailed to national random samples of seniors. Of 2,434 deliverable surveys, 946 (39%) were returned, and 700 (29%) provided usable data. Data were collected in 2015 via an online survey sent to a national sample of adults. Of 26,173 usable responses, 3,933 were aged 65 years or older. Descriptive statistics and logistic regression analyses described relationships among study variables. RESULTS: Results showed that the proportion of seniors without prescription coverage was 9% in 2015, a decrease from 29% in 2001 and 32% in 1998. The proportion of senior citizens reporting financial hardship from medication purchases was 36% in 2015, a rise from 31% in 2001 and 19% in 1998. For those without prescription drug coverage, 34%, 55%, and 49% reported financial hardship in 1998, 2001, and 2015, respectively. For those with drug coverage, 12%, 22%, and 35% reported financial hardship in 1998, 2001, and 2015, respectively. CONCLUSIONS: After implementation of Medicare Part D and the ACA, the proportion of seniors without prescription drug coverage decreased. However, self-reported financial hardship from purchasing medications increased. Senior citizens with prescription drug insurance may be experiencing financial hardship from increasing out-of-pocket costs for insurance premiums, cost sharing, and full-cost obligation for some medications. DISCLOSURES: Funding was provided by the American Association of Colleges of Pharmacy New Investigator Program, the University of Minnesota Grant in-Aid of Research Program, and the Peters Endowment for Pharmacy Practice Innovation. The authors have no conflicts of interest to declare. Schommer, Mott, and Brown contributed to study design and collected the data, with assistance from Olson. Data interpretation was performed by Olson, Schommer, Mott, and Brown. The manuscript was written and revised by Olson, Schommer, Mott, and Brown. PMID- 27668564 TI - Overview of Comprehensive Hepatitis C Virus Medication Management in a State Medicaid Program. AB - BACKGROUND: Breakthrough direct-acting antivirals set a new standard in the management of hepatitis C virus (HCV) with regard to cure rates and improved tolerability; however, the health care system is challenged by the cost of these medications. OBJECTIVE: To describe the effect of a comprehensive HCV medication management program on optimized regimen use, prior authorization (PA) modifications, and medication cost avoidance in a state Medicaid program. METHODS: This program consists of a 2-tiered prescriber outreach: (1) regimen outreach to promote optimized regimen selection and (2) refill outreach to support medication adherence. PA criteria were developed to identify optimized regimens, taking into account member- and virus-specific factors as well as cost. Prescriber outreach was conducted to recommend the use of an optimized regimen as applicable. Successful regimen outreach was defined as the number of members for whom a recommendation was accepted. A refill report identified members without a subsequent paid HCV medication claim within 25 days of the previous claim and outreach to the prescriber's office was performed. The outcome measure for refill outreach was the number and type of PA modifications made secondary to outreach (closure or extension). Cost avoidance was calculated for members who completed treatment with an optimized regimen. Return on investment (ROI) was calculated for the program. RESULTS: Between December 18, 2013, and January 31, 2015, 911 members had PA requests approved for simeprevir, sofosbuvir, or ledipasvir/ sofosbuvir. Of these members, 223 (24.5%) met the criteria for regimen outreach. Pharmacist interventions to treat with an optimized regimen were accepted for 135 members (60.5%). Following implementation of prescriber outreach to promote refills, between March 10, 2014, and January 31, 2015, offices were informed of an upcoming refill for 515 members. As a result of outreach, 19.6% of members had a subsequent PA modification. Sixty-nine approved PAs (for 68 members) were closed after correspondence with the prescriber, and 33 approved PAs (for 33 members) were extended. The total projected cost avoidance was $3,770,097. The comprehensive HCV medication management program demonstrated an ROI of $10.28 for every $1 spent. CONCLUSIONS: A comprehensive HCV medication management program can help contain costs while ensuring that members have access to most clinically appropriate regimens. DISCLOSURES: No outside funding supported this study. Lavitas reports personal fees and nonfinancial support from University of Tennessee, Advanced Studies in Medicine and grant funding from Bristol-Myers Squibb, outside the submitted work. All other authors report no conflicts of interest. The poster "Overview of a Hepatitis C Medication Monitoring Program in a State Medicaid Program" was presented October 8, 2014, by Lavitas at the AMCP Nexus 2014 meeting in Boston, Massachusetts. A program update was presented at the 2015 American Drug Utilization Review Society Meeting on February 27, 2015. Study concept and design were contributed by Price, Lenz, and Jeffrey, with assistance from Lavitas, Tesell, and Hydery. Lavitas, Tesell, and Hydery collected the data, assisted by Price, Lenz, and Jeffrey, and data interpretation was performed by all authors. The manuscript was written by Greenwood, Lavitas, Tesell, and Hydery, with assistance from the other authors, and was revised by all authors. PMID- 27668565 TI - Impact of Pharmacy Intervention on Prior Authorization Success and Efficiency at a University Medical Center. AB - BACKGROUND: Prior authorizations (PAs) may improve appropriate use of prescription medications. Despite potential savings for health insurance plans, the PA process is time consuming for the ordering provider, pharmacy, and patient. The UC Davis Health System (UCDHS) has created a centralized pharmacy run clinic PA process. OBJECTIVE: To compare the mean PA processing time between the new centralized clinic and usual care and provide secondary endpoints for PA approval rates, time to prescription fill, time to prescription pick-up, total staff time, and estimated labor costs. METHODS: This is a prospective observational study comparing sequential PA requests at the UCDHS centralized clinic (intervention) and other UCDHS clinics (usual care) between January 1, 2014, and December 31, 2014. The Cochran-Mantel-Haenszel test was used to compare dichotomous outcomes (approval/denial rates) between the 2 groups, controlling for insurance type. A generalized linear model was applied for comparing the continuous outcomes (PA process time, time to first fill, time to pick-up, and cost) with insurance type as covariate. RESULTS: For the intervention group, 47 PAs were evaluated, and 77 PAs were evaluated in the usual care group. The average PA process time was 0.53 days for the intervention group versus 7.02 days for usual care (P < 0.001), and the PA approval rate was 93% for the intervention group versus 68% for usual care (P < 0.002). The mean time to fill was 2.49 days and 5.52 days for the intervention and usual care clinics, respectively (P = 0.02). The pick-up percentage was 75% versus 52% for intervention and usual care, respectively (P < 0.001). The intervention clinic spent a significantly lower mean time processing PAs (15 minutes vs. 64 minutes) compared with the usual care clinics (P < 0.001). It is estimated that the mean total labor cost per PA at the intervention clinic was $11.50 compared with $37.50 for the usual care clinics (P < 0.001). CONCLUSIONS: Pharmacy-led interventions in PA processing resulted in a statistically significant benefit in improving time to PA approval, time to first fill, and time to pick-up. DISCLOSURES: No outside funding supported this study. The authors report no conflicting interests. Melnikow and Cutler contributed the study concept and design, with assistance from the other authors. Lester, Barca, and She collected the data, and Xin performed all statistical analysis. Cutler was the major contributor to manuscript preparation, with assistance from the other authors. PMID- 27668566 TI - Variation in Private Payer Coverage of Rheumatoid Arthritis Drugs. AB - BACKGROUND: Payers in the United States issue coverage determinations to guide how their enrolled beneficiaries use prescription drugs. Because payers create their own coverage policies, how they cover drugs can vary, which in turn can affect access to care by beneficiaries. OBJECTIVE: To examine how the largest private payers based on membership cover drugs indicated for rheumatoid arthritis and to determine what evidence the payers reported reviewing when formulating their coverage policies. METHODS: Coverage policies issued by the 10 largest private payers that make their policies publicly available were identified for rheumatoid arthritis drugs. Each coverage determination was compared with the drug's corresponding FDA label and categorized according to the following: (a) consistent with the label, (b) more restrictive than the label, (c) less restrictive than the label, or (d) mixed (i.e., more restrictive than the label in one way but less restrictive in another). Each coverage determination was also compared with the American College of Rheumatology (ACR) 2012 treatment recommendations and categorized using the same relative restrictiveness criteria. The policies were then reviewed to identify the evidence that the payers reported reviewing. The identified evidence was divided into the following 6 categories: randomized controlled trials; other clinical studies (e.g., observational studies); health technology assessments; clinical reviews; cost-effectiveness analyses; and clinical guidelines. RESULTS: Sixty-nine percent of coverage determinations were more restrictive than the corresponding FDA label; 15% were consistent; 3% were less restrictive; and 13% were mixed. Thirty-four percent of coverage determinations were consistent with the ACR recommendations, 33% were more restrictive; 17% were less restrictive; and 17% were mixed. Payers most often reported reviewing randomized controlled trials for their coverage policies (an average of 2.3 per policy). The payers reported reviewing an average of 1.4 clinical guidelines, 1.1 clinical reviews, 0.8 other clinical studies, and 0.5 technology assessments per policy. Only 1 payer reported reviewing cost effectiveness analyses. The evidence base that the payers reported reviewing varied in terms of volume and composition. CONCLUSIONS: Payers most often covered rheumatoid arthritis drugs more restrictively than the corresponding FDA label indication and the ACR treatment recommendations. Payers reported reviewing a varied evidence base in their coverage policies. DISCLOSURES: Funding for this study was provided by Genentech. Chambers has participated in a Sanofi advisory board, unrelated to this study. The authors report no other potential conflicts of interest. Study concept and design were contributed by Chambers. Anderson, Wilkinson, and Chenoweth collected the data, assisted by Chambers, and data interpretation was primarily performed by Chambers, along with Anderson and with assistance from Wilkinson and Chenoweth. The manuscript was written primarily by Chambers, along with Wilkinson and with assistance from Anderson and Chenoweth. Chambers, Chenoweth, Wilkinson, and Anderson revised the manuscript. PMID- 27668567 TI - Predictors of Appropriate Pharmacotherapy Management of COPD Exacerbations and Impact on 6-Month Readmission. AB - BACKGROUND: Suboptimal treatment of exacerbations is a major concern in management of chronic obstructive pulmonary disease (COPD). The Pharmacotherapy Management of COPD Exacerbation (PCE) Healthcare Effectiveness Data and Information Set (HEDIS) measure is a quality measure included by the National Committee for Quality Assurance that focuses on appropriate use of steroids and bronchodilators during an acute COPD exacerbation. There is limited evidence evaluating predictors of this quality measure, as well as its association with hospital readmission and cost outcomes. OBJECTIVES: To (a) describe characteristics of patients hospitalized for COPD, (b) evaluate factors associated with appropriate receipt of pharmacotherapy upon discharge, and (c) evaluate factors associated with the rate of readmission. METHODS: In this retrospective, observational, event-based study of COPD-related hospital and ED visits, events were identified between 2007 and 2013 from a Central Texas health plan using administrative claims data. The index date was defined as the date of admission. Subjects were included if they were aged >= 40 years and had a medical claim with a primary diagnosis for COPD or a pharmacy claim for a COPD maintenance medication during the 1-year pre-index period. Study groups were identified based on the receipt of PCE within the time frame specified by HEDIS: (a) a systemic corticosteroid within 14 days of discharge (PCE-C) or (b) a bronchodilator within 30 days of discharge (PCE-D). Bivariate analyses of potential factors associated with the receipt of PCE were performed using t-tests for continuous data and chi-square tests for categorical data. Generalized estimating equations, including significant predictors from the bivariate analyses, were used to determine factors associated with receipt of PCE-C and/or PCE-D, as well association with COPD-related and all-cause readmission within 6 months of discharge. RESULTS: Of 375 identified index admissions, 254 (68%) patients received PCE-C; 299 (80%) received PCE-D; and 229 (61%) received both. Patients were more likely to receive PCE with an index inpatient visit as compared with an ED visit (PCE-C: RR = 2.25, 95% CI = 1.21-4.17, P = 0.010; PCE D: RR = 1.90, 95% CI = 1.01-3.58, P = 0.048). Those with previous use of rescue medication were also more likely to receive PCE (PCE-C: RR = 1.88, 95% CI = 1.12 3.17, P = 0.018; PCE-D: RR = 2.11, 95% CI = 1.16-3.83, P = 0.014). Patients with greater adherence (proportion of days covered [PDC] >= 75%) to COPD maintenance medication before admission (RR = 8.67, 95% CI = 1.60-46.78, P = 0.012) were also more likely to receive PCE-D. Older patients were more likely to have a COPD related readmission (RR = 1.07, 95% CI = 1.01-1.13, P = 0.028), while use of maintenance medication before admission was associated with lower risk of an all cause readmission (RR = 0.49, 95% CI = 0.30-0.79, P = 0.004). In addition, patients with higher medical and pharmacy costs before the index event were more likely to have all-cause readmission (RR = 1.01, 95% CI = 1.00-1.02, P = 0.013). Receipt of PCE was not shown to be a significant predictor of all-cause or COPD related readmission. CONCLUSIONS: The use of bronchodilators and systemic corticosteroids after a COPD-related inpatient or ED visit may be related to the severity of the index COPD exacerbation or patients' previous pattern of bronchodilator use. However, the use of maintenance medication before the index event was associated with a significant reduction in all-cause readmission, so proper treatment of the underlying disease may be an effective strategy in reducing readmission. DISCLOSURES: Funding for this study was provided by GlaxoSmithKline (HO-14-15081). Tran was a Fellow at Scott & White Health Plan (SWHP) during year 1 of this study and a Fellow at Novartis during year 2 of this study. Novartis did not have any input in this study nor did it contribute any funding or support for this research. Tran, Xiang, Godley, and Stock were employed by SWHP at the time of this study. Rascati is employed by the University of Texas at Austin and also by the Journal of Managed Care & Specialty Pharmacy and has received consulting fees from GlaxoSmithKline. Coleman, Bogart, and Stanford are GlaxoSmithKline employees and shareholders. Study design was created by Rascati, Tran, and Godley, with assistance from Stock, Coleman, Bogart, and Stanford. Tran and Xiang collected the data, with data analysis and interpretation performed by Stock and Rascati. The manuscript was written by Tran, Rascati, and Xiang and revised by Godley, Stock, Coleman, Bogart, and Stanford. PMID- 27668568 TI - Biopsy Procedures and Molecular Testing Utilization and Related Costs in Patients with Metastatic Lung Cancer. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements are key therapeutic targets for biomarker-driven treatment with an EGFR or ALK tyrosine kinase inhibitor (TKI) in patients with metastatic non-small cell lung cancer (NSCLC). To appropriately guide treatment decisions, since 2011, the National Comprehensive Cancer Network and the American Society of Clinical Oncology therefore recommend EGFR and ALK analysis in tumor samples obtained at the time of diagnosis in patients with non squamous NSCLC. Currently, there are limited data on utilization patterns and cost of biopsy procedures and biomarker tests in patients with metastatic NSCLC who receive an EGFR or ALK TKI. OBJECTIVES: To (a) describe utilization patterns and costs associated with biopsy procedures and biomarker testing in patients with NSCLC who received erlotinib or crizotinib between 2009 and 2012 and (b) investigate the timing of these procedures relative to the erlotinib or crizotinib index date. METHODS: Adult patients with metastatic lung cancer were identified by ICD-9-CM diagnostic codes within the Truven Health Analytic MarketScan database. Patients were included in the analysis if they had an index erlotinib or crizotinib claim between January 1, 2009, and September 30, 2012 (index period) and were continuously enrolled for >= 12 months before the index claim. Because there is no specific ICD-9-CM diagnostic code for NSCLC, patients with metastatic lung cancer who received erlotinib or crizotinib were considered to have metastatic NSCLC. Using CPT and ICD-9-CM codes, lung biopsy procedures performed during the 24 months before or 12 months after the index claim date were identified. For every patient, biomarker testing claims for EGFR and ALK were identified using the molecular pathology stacked CPT code during the 2 months before or 1 month after the index date. The frequency of claims for biopsy procedures and biomarker testing was analyzed descriptively. The overall summary measures for biomarker testing, especially frequency of EGFR testing in patients receiving erlotinib, was also described as before and after 2011, the year when biomarker testing became part of the guidelines. Per patient and overall costs for biopsy procedures and biomarker testing were calculated from payer and patient perspectives. RESULTS: Of the 4,926 identified patients, 4,801 (97.5%) received erlotinib, and 125 (2.5%) received crizotinib. Biopsy procedure claims were identified for 3,579 (72.7%) patients, including 3,503 (73.0%) erlotinib recipients and 76 (60.8%) crizotinib recipients. Biomarker testing claims were identified for 675 (13.7%) patients, including 634 (13.2%) erlotinib recipients and 41 (32.8%) crizotinib recipients. Overall, most biomarker testing procedures (476 of 741) were identified in 435 (of 675) patients after year 2011. Also, among erlotinib recipients, percentage of patients receiving EGFR testing was increased over the index period. Per patient mean (SD) numbers of biopsy procedures and biomarker tests were 1.2 (1.1) and 0.2 (0.4), respectively. In the outpatient setting, per patient mean (SD) cost per biopsy procedure was $1,223 ($1,899) from the payer perspective and $60 ($147) from the patient perspective, whereas in the inpatient setting, it was $8,163 ($18,712) and $180 ($691), respectively. Among patients receiving at least 1 biomarker test, the per patient mean (SD) cost for the overall population was $891 ($1,062) and $43 ($229); for erlotinib recipients, it was $906 ($1,084) and $42 ($228); and for crizotinib recipients, it was $664 ($576) and $55 ($243) in payer and patient perspectives, respectively. CONCLUSIONS: This study provides insight into the use and cost of biopsy and biomarker testing procedures in patients with metastatic NSCLC. The low frequency of biomarker testing highlights the need for more awareness of testing to guide treatment decisions in these patients. Costs associated with biopsy procedures and biomarker testing provide insight into the economic impact on metastatic NSCLC patients treated with targeted therapy. DISCLOSURES: This study was sponsored by Merck & Co. Shinde is a study manager working for Merck under contract with AllSourcePPS, an Agile 1 company in Huntington Beach, California. Cao and Kothari are employees of Merck & Co., Kenilworth, New Jersey. Study concept and design were contributed primarily by Shinde and Kothari. Data analysis was performed by Cao. Data interpretation was performed by Shinde, Cao, and Kothari. Shinde wrote the manuscript with assistance from Cao and Kothari. The revision was completed primarily by Shinde and Kothari. PMID- 27668569 TI - Comparing Clinical and Economic Outcomes Associated with Early Initiation of Combination Therapy of an Alpha Blocker and Dutasteride or Finasteride in Men with Benign Prostatic Hyperplasia in the United States. AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in men that is characterized by lower urinary tract symptoms. Pharmacologic treatment with alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) is recommended to alleviate symptoms, prevent disease progression that can lead to complications, and reduce health care costs. OBJECTIVE: To compare clinical, economic, and health care resource utilization outcomes among BPH patients treated with early continuous combination AB and 5ARI therapy (dutasteride vs. finasteride) using administrative claims data from the United States. METHODS: A retrospective analysis of administrative claims data from 2003-2013 was conducted to compare outcomes between patients with claims for early combination therapy with dutasteride + AB and patients with claims for early finasteride + AB. The study population included males aged older than 50 years with at least 1 medical claim with a diagnosis of BPH and pharmacy dispensing for AB and 5ARI therapies. Outcomes included acute urinary retention (AUR), prostate-related surgery, clinical progression, medical and pharmacy costs, and health care resource utilization. Inverse probability of treatment (IPT) weighted Cox proportional hazards, linear, and Poisson regression models were used to assess the association between outcomes and early combination therapy as appropriate. RESULTS: A total of 2,778 patients were included in the early finasteride + AB treatment cohort, and 4,125 patients were included in the early dutasteride + AB cohort. Dutasteride users were younger than finasteride users (mean age: 64.8 vs. 67.5 years, P < 0.001) and had a greater mean number of urologist visits (10.7 vs. 7.9, P < 0.001) during baseline. After adjusting for confounding using IPT weighting, no statistically significant difference was observed between dutasteride and finasteride for AUR (hazard ratio [HR] = 0.845, 95% CI = 0.660 1.070, P = 0.1643), prostate-related surgery (HR = 0.806, 95% CI = 0.568-1.171, P = 0.2525), and clinical progression (HR = 0.834, 95% CI = 0.663-1.043, P = 0.1122). While dutasteride was associated with higher pharmacy costs per month (adjusted monthly cost difference = $79, 95% CI = $45-$105), total all-cause medical costs were not significantly different between the 2 cohorts (adjusted monthly cost difference = -$44, 95% CI = -$110-$22). CONCLUSIONS: Clinical and economic outcomes were similar between the early dutasteride + AB and early finasteride + AB cohorts, with no statistically significant differences detected. DISCLOSURES: Funding for this study was provided by GlaxoSmithKline (HO-14-15325 and AVO110072). Bell and Swensen are employees of GlaxoSmithKline. DerSarkissian, Xiao, Duh, and Lefebvre are employed by Analysis Group, a consulting company that received research grants from GlaxoSmithKline to conduct this study. Study concept and design were contributed by Bell, Swensen, Lefebvre, and Duh. Bell and Duh acquired the data. DerSarkissian and Xiao performed the statistical analysis and interpreted the data along with Lefebvre, Duh, and Bell. DerSarkissian and Bell drafted the manuscript. All authors contributed equally to critically revising the manuscript and providing final approval of the submitted manuscript. PMID- 27668570 TI - Plasma inactivation of microorganisms on sprout seeds in a dielectric barrier discharge. AB - Fresh produce is frequently contaminated by microorganisms, which may lead to spoilage or even pose a threat to human health. In particular sprouts are considered to be among the most risky foods sold at retail since they are grown in an environment practically ideal for growth of bacteria and usually consumed raw. Because heat treatment has a detrimental effect on the germination abilities of sprout seeds, alternative treatment technologies need to be developed for microbial inactivation purposes. In this study, non-thermal plasma decontamination of sprout seeds is evaluated as a promising option to enhance food safety while maintaining the seed germination capabilities. In detail, investigations focus on understanding the efficiency of non-thermal plasma inactivation of microorganisms as influenced by the type of microbial contamination, substrate surface properties and moisture content, as well as variations in the power input to the plasma device. To evaluate the impact of these parameters, we studied the reduction of native microbiota or artificially applied E. coli on alfalfa, onion, radish and cress seeds exposed to non-thermal plasma in an atmospheric pressure pulsed dielectric barrier discharge streamed with argon. Plasma treatment resulted in a maximum reduction of 3.4 logarithmic units for E. coli on cress seeds. A major challenge in plasma decontamination of granular food products turned out to be the complex surface topology, where the rough surface with cracks and crevices can shield microorganisms from plasma generated reactive species, thus reducing the treatment efficiency. However, improvement of the inactivation efficiency was possible by optimizing substrate characteristics such as the moisture level and by tuning the power supply settings (voltage, frequency) to increase the production of reactive species. While the germination ability of alfalfa seeds was considerably decreased by harsh plasma treatment, enhanced germination was observed under mild conditions. In conclusion, the results from this study indicate that cold plasma treatment represents a promising technology for inactivation of bacteria on seeds used for sprout production while preserving their germination properties. PMID- 27668571 TI - Increased proportions of Tc17 cells and NK cells may be risk factors for disease progression in Hashimoto's thyroiditis. AB - Both cellular and humoral responses play important roles in the pathogenesis of Hashimoto's thyroiditis (HT). However, the immunological differences between euthyroid (mild HT) and hypothyroid (severe HT) patients are unknown. This study aimed to investigate the distribution of lymphocyte subsets and cytokine profiles in HT patients with differences in thyroid function. Peripheral blood was drawn from 18 healthy controls and 54 HT patients (33 patients with mild HT, 21 patients with severe HT). The percentages of B cell subsets, T cell subsets and NK cells were analyzed by flow cytometry. The levels of IL-21 and Bcl-6 mRNA were assessed using real-time PCR. The levels of serum IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10 and a proliferation-inducing ligand (APRIL) were measured by ELISA or cytometric bead array. The percentages of double-negative memory B cells, plasma cells, Tfh cells and Tc17 cells were higher in HT patients than in the healthy controls. The percentages of Tc17 cells and NK cells were higher in the patients with severe HT than in the patients with mild HT. The levels of serum APRIL, IL-6 and IL-10 were higher in the patients with severe HT than in those with mild HT. The percentage of NK cells was positively correlated with TSH levels in the HT patients. Our data indicate that the distribution of lymphocyte subsets and cytokine profiles is aberrant in HT patients, and the increased percentages of Tc17 cells and NK cells and increased cytokine levels might be involved in the progression of HT. PMID- 27668572 TI - Effects of prolonged vibration to vastus intermedius muscle on force steadiness of knee extensor muscles during isometric force-matching task. AB - Afferent inputs from Ia fibers in muscle spindles are essential for the control of force and prolonged vibration has been applied to muscle-tendon units to manipulate the synaptic input from Ia afferents onto alpha-motor neurons. The vastus intermedius (VI) reportedly provides the highest contribution to the low level knee extension torque among the individual synergists of quadriceps femoris (QF). The purpose of the present study was to examine the effect of prolonged vibration to the VI on force steadiness of the QF. Nine healthy men (25.1+/ 4.3years) performed submaximal force-matching task of isometric knee extension for 15s before and after mechanical vibration to the superficial region of VI for 30min. Target forces were 2.5%, 10%, and 30% of maximal voluntary contraction (MVC), and force steadiness was determined by the coefficient of variation (CV) of force. After the prolonged VI vibration, the CV of force at 2.5%MVC was significantly increased, but CVs at 10% and 30%MVCs were not significantly changed. The present study concluded that application of prolonged vibration to the VI increased force fluctuations of the QF during a very low-level force matching task. PMID- 27668573 TI - Validation of a DNA methylation reference panel for the estimation of nucleated cells types in cord blood. AB - Cord blood is widely used as surrogate tissue in epigenome-wide association studies of prenatal conditions. Cell type composition variation across samples can be an important confounder of epigenome-wide association studies in blood that constitute a mixture of cells. We evaluated a newly developed cord blood reference panel to impute cell type composition from DNA methylation levels, including nucleated red blood cells (nRBCs). We estimated cell type composition from 154 unique cord blood samples with available DNA methylation data as well as direct measurements of nucleated cell types. We observed high correlations between the estimated and measured composition for nRBCs (r = 0.92, R2 = 0.85), lymphocytes (r = 0.77, R2 = 0.58), and granulocytes (r = 0.72, R2 = 0.52), and a moderate correlation for monocytes (r = 0.51, R2 = 0.25) as well as relatively low root mean square errors from the residuals ranging from 1.4 to 5.4%. These results validate the use of the cord blood reference panel and highlight its utility and limitations for epidemiological studies. PMID- 27668576 TI - Effect of dexmedetomidine hydrochloride on tiletamine hydrochloride-zolazepam hydrochloride anesthesia in alpacas. AB - OBJECTIVE To evaluate the effect of IM administration of a tiletamine hydrochloride-zolazepam hydrochloride (TZ) combination with either dexmedetomidine hydrochloride or saline (0.9% NaCl) solution (SS) on the motor response to claw clamping, selected cardiorespiratory variables, and quality of recovery from anesthesia in alpacas. ANIMALS 5 adult sexually intact male alpacas. PROCEDURES Each alpaca was given the TZ combination (2 mg/kg) with dexmedetomidine (5 [D5], 10 [D10], 15 [D15], or 20 [D20] ug/kg) or SS IM at 1 week intervals (5 experiments); motor response to claw clamping was assessed, and characteristics of anesthesia, recovery from anesthesia, and selected cardiorespiratory variables were recorded. RESULTS Mean +/- SEM duration of lack of motor response to claw clamping was longest when alpacas received treatments D15 (30.9 +/- 5.9 minutes) and D20 (40.8 +/- 5.9 minutes). Duration of lateral recumbency was significantly longer with dexmedetomidine administration. The longest time (81.3 +/- 10.4 minutes) to standing was observed when alpacas received treatment D20. Following treatment SS, 4 alpacas moved in response to claw clamping at the 5-minute time point. Heart rate decreased from pretreatment values in all alpacas when dexmedetomidine was administered. Treatments D10, D15, and D20 decreased Pao2, compared with treatment SS, during the first 15 minutes. During recovery, muscle stiffness and multiple efforts to regain a sternal position were observed in 3 SS-treated and 1 D5-treated alpacas; all other recoveries were graded as excellent. CONCLUSIONS AND CLINICAL RELEVANCE In TZ anesthetized alpacas, dexmedetomidine (10, 15, and 20 ug/kg) administered IM increased the duration of lack of motor response to claw clamping, compared with the effect of SS. PMID- 27668577 TI - Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. AB - OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm. PMID- 27668578 TI - In vitro biomechanical evaluation of four surgical techniques for fusion of equine centrodistal and tarsometatarsal joints. AB - OBJECTIVE To evaluate the biomechanical properties of 4 methods for fusion of the centrodistal and tarsometatarsal joints in horses and compare them among each other and with control tarsi. SAMPLE 24 sets of paired tarsi without substantial signs of osteoarthritis harvested from equine cadavers. PROCEDURES Test constructs (n = 6/type) were prepared from 1 tarsus from each pair to represent surgical drilling; 2 medially to laterally placed kerf-cut cylinders (MLKCs); a single large, dorsally applied kerf-cut cylinder (DKC); and a dorsomedially applied locking compression plate (DMLCP). Constructs and their contralateral control tarsi were evaluated in 4-point bending in the dorsoplantar, lateromedial, and mediolateral directions; internal and external rotation; and axial compression. Bending, torsional, and axial stiffness values were calculated. RESULTS Mean stiffness values were consistently lower for surgical drilling constructs than for contralateral control tarsi. Over all biomechanical testing, surgical drilling significantly reduced joint stability. The MLKC constructs had superior biomechanical properties to those of control tarsi for 4 point bending but inferior properties for external and internal rotation. The DMLCP and DKC constructs were superior to control tarsi in dorsoplantar, rotational, and axial compression directions only; DMLCP constructs had no superior stiffness in lateromedial or mediolateral directions. Only the DKC constructs had greater stiffness in the mediolateral direction than did control tarsi. Over all biomechanical testing, DMLCP and DKC constructs were superior to the other constructs. CONCLUSIONS AND CLINICAL RELEVANCE These biomechanical results suggested that a surgical drilling approach to joint fusion may reduce tarsal stability in horses without clinical osteoarthritis, compared with stability with no intervention, whereas the DMLCP and DKC approaches may significantly enhance stability. PMID- 27668579 TI - Computed tomographic findings of pulmonary atelectasis in healthy anesthetized Beagles. AB - OBJECTIVE To characterize the extent and location of atelectasis in healthy anesthetized dogs positioned in lateral recumbency and to determine whether repositioning dogs in sternal recumbency would resolve atelectasis. ANIMALS 6 healthy adult Beagles. PROCEDURES Each dog was anesthetized and underwent a CT examination twice with a 2-week interval between examinations. Once anesthetized, each dog was positioned in sternal recumbency, and a breath-hold helical transverse thoracic CT scan was acquired. The dog was then positioned in lateral recumbency for 30 minutes, and images were obtained at 5 preselected sites at 3, 8, 13, 20, and 30 minutes after repositioning (phase 1). Then, the dog was repositioned in sternal recumbency, and CT images were obtained at the 5 preselected sites at 5, 10, and 20 minutes after repositioning (phase 2). The protocol for the second examination was the same as the first except the dog was positioned in the opposite lateral recumbency during phase 1. The attenuation and cross-sectional area of the lung lobes at the preselected sites were measured and compared over time. RESULTS Lateral recumbency did not cause atelectasis in any of the dogs. Patchy areas of abnormally increased attenuation were infrequently detected in the left cranial lung lobe when dogs were positioned in left lateral recumbency, and those areas failed to resolve when dogs were positioned in sternal recumbency. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the extent of lung attenuation changes was minimal in healthy anesthetized Beagles positioned in lateral recumbency and should not preclude CT examination. PMID- 27668580 TI - Estimation of time to peak contrast enhancement of the aorta and liver for dual phase computed tomography on the basis of contrast medium arrival time, injection duration, and injection technique in dogs. AB - OBJECTIVE To evaluate the accuracy of estimating time to peak enhancement (TPE) of the aorta and liver parenchyma on the basis of contrast medium arrival time in the aorta, injection duration, and injection technique in dogs. ANIMALS 18 dogs of specific body weight categories (>= 2 dogs/category) with no liver abnormalities detected via CT. PROCEDURES Dogs were randomly assigned within weight categories to receive contrast medium IV at a fixed injection rate (5 mL/s) or fixed injection duration (20 seconds). Time-contrast attenuation curves were generated from dynamic CT scans acquired at the hepatic hilus. Data collected for contrast medium arrival time and injection duration were used to estimate TPEs of the aorta and liver, and results were compared with the observed TPEs for the aorta and liver. RESULTS Contrast medium arrival time, injection duration, and injection technique were significantly associated with observed values for aortic TPE and explained 96.1% of variation in TPE. For the fixed rate technique, the regression equation for estimating aortic TPE was 0.8 * (injection duration + contrast medium arrival time) + 1.6. For the fixed duration technique, the regression equation changed by only the constant (-2.6). However, the hepatic TPE estimated from the 3 predictor variables was not significantly different from the mean of observed TPEs. CONCLUSIONS AND CLINICAL RELEVANCE Aortic TPE could be accurately estimated from contrast medium arrival time, injection duration, and injection technique in dogs with apparently healthy livers. The regression equations derived from this relationship can be used to improve the efficiency of dual-phase CT of the liver in dogs. PMID- 27668581 TI - Serum cholecystokinin concentrations in dogs with naturally acquired pituitary dependent hyperadrenocorticism. AB - OBJECTIVE To determine serum cholecystokinin (CCK) concentrations in dogs with pituitary-dependent hyperadrenocorticism (PDH) and to evaluate associations among CCK concentration, PDH, and gallbladder mucocele (GBM). ANIMALS 14 client-owned dogs with PDH and 14 healthy dogs. PROCEDURES Dogs were separated into 4 groups: healthy dogs without gallbladder sludge (group A; n = 7), healthy dogs with gallbladder sludge (group B; 7), dogs with PDH and gallbladder sludge (group C; 8), and dogs with PDH and GBM (group D; 6). Serum CCK concentrations were then measured before and 1, 2, and 4 hours after consumption of a high-fat meal. Concentrations in dogs with PDH were also measured before and after trilostane treatment. Results were compared among groups and assessment points. RESULTS Preprandial serum CCK concentrations in group C were significantly lower than those in groups A, B, and D, but no significant differences in postprandial CCK concentrations were identified among the groups 1, 2, or 4 hours after the meal. With respect to trilostane treatment of dogs with PDH, no significant differences were identified between pre- and post-trilostane serum CCK concentrations in group C or D. Median CCK concentration after trilostane treatment was higher in group D than in group C, but this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE The outcomes in this study did not support the hypothesis that a low circulating CCK concentration affects the development of GBM in dogs with PDH. PMID- 27668583 TI - Evaluation of the dynactin 1 gene in Leonbergers and Labrador Retrievers with laryngeal paralysis. AB - OBJECTIVE To sequence exons and splice consensus sites of the dynactin subunit 1 (DCTN1) gene in Leonbergers and Labrador Retrievers with clinical laryngeal paralysis. ANIMALS 5 unrelated Leonbergers with laryngeal paralysis, 2 clinically normal Leonbergers, 7 unrelated Labrador Retrievers with laryngeal paralysis, and 2 clinically normal Labrador Retrievers. PROCEDURES Primers were designed for the entire coding regions of the DCTN1 gene, a noncoding exon at the 5' end of the gene, and a 900-bp single-nucleotide polymorphism (SNP)-rich region located 17 kb upstream of the DCTN1 gene by use of the CanFam3 assembly of the canine genome sequence. Sequences were generated and compared between clinically normal and affected dogs. The SNPs flanking the DCTN1 gene as well as a previously identified nonsynonymous SNP in exon 32 were genotyped in affected and clinically normal Leonbergers and Labrador Retrievers. RESULTS None of the affected dogs were homozygous for any mutation affecting coding regions or splicing consensus sequences. Of the 16 dogs tested for the missense SNP in exon 32, all were homozygous for the reference allele, except for 2 affected and 1 clinically normal Labrador Retriever and 1 clinically normal Leonberger. The DCTN1 gene sequences (5 dogs) and haplotypes of polymorphic markers surrounding the DCTN1 gene (all dogs) were not consistent with the hypothesis that laryngeal paralysis was associated with inheritance of the same DCTN1 disease-causing allele within all Labrador Retrievers or Leonbergers evaluated. CONCLUSIONS AND CLINICAL RELEVANCE Mutations in the DCTN1 gene did not appear to cause laryngeal paralysis in Leonbergers or Labrador Retrievers. PMID- 27668582 TI - Evaluation of the minimum infectious dose of porcine epidemic diarrhea virus in virus-inoculated feed. AB - OBJECTIVE To determine the minimum infectious dose of porcine epidemic diarrhea virus (PEDV) in virus-inoculated feed. ANIMALS 30 crossbred 10-day-old pigs. PROCEDURES Tissue culture PEDV was diluted to form 8 serial 10-fold dilutions. An aliquot of stock virus (5.6 * 10(5) TCID50/mL) and each serial PEDV dilution were mixed into 4.5-kg batches of feed to create 9 PEDV-inoculated feed doses; 1 virus negative dose of culture medium in feed was also created. Pigs were challenge exposed via oral administration of PEDV-inoculated feed, and fecal swab specimens were collected. All pigs were euthanized 7 days after challenge exposure; fresh tissues were collected and used for PCR assay, histologic examination, and immunohistochemical analysis. RESULTS The PCR cycle threshold (Ct) decreased by approximately 10 when PEDV was added to feed, compared with results for equivalent PEDV diluted in tissue culture medium. Pigs became infected with PEDV when challenge exposed with the 4 highest concentrations (lowest concentration to cause infection, 5.6 * 10(1) TCID50/g; Ct = 27 in tissue culture medium and 37 in feed). CONCLUSIONS AND CLINICAL RELEVANCE In this study, PEDV in feed with detectable Ct values of 27 to 37 was infective. The Ct was 37 for the lowest infective PEDV dose in feed, which may be above the limit of detection established for PEDV PCR assays used by some diagnostic laboratories. Overall, results indicated 5.6 * 10(1) TCID50/g was the minimum PEDV dose in feed that can lead to infection in 10-day-old pigs under the conditions of this study. PMID- 27668584 TI - An attempt to detect lameness in galloping horses by use of body-mounted inertial sensors. AB - OBJECTIVE To evaluate head, pelvic, and limb movement to detect lameness in galloping horses. ANIMALS 12 Thoroughbreds. PROCEDURES Movement data were collected with inertial sensors mounted on the head, pelvis, and limbs of horses trotting and galloping in a straight line before and after induction of forelimb and hind limb lameness by use of sole pressure. Successful induction of lameness was determined by measurement of asymmetric vertical head and pelvic movement during trotting. Differences in gallop strides before and after induction of lameness were evaluated with paired-sample statistical analysis and neural network training and testing. Variables included maximum, minimum, range, and time indices of vertical head and pelvic acceleration, head rotation in the sagittal plane, pelvic rotation in the frontal plane, limb contact intervals, stride durations, and limb lead preference. Difference between median standardized gallop strides for each limb lead before and after induction of lameness was calculated as the sum of squared differences at each time index and assessed with a 2-way ANOVA. RESULTS Head and pelvic acceleration and rotation, limb timing, stride duration measurements, and limb lead preference during galloping were not significantly different before and after induction of lameness in the forelimb or hind limb. Differences between limb leads before induction of lameness were similar to or greater than differences within limb leads before and after lameness induction. CONCLUSIONS AND CLINICAL RELEVANCE Galloping horses maintained asymmetry of head, pelvic, and limb motion between limb leads that was unrelated to lameness. PMID- 27668586 TI - Effects of topical ocular application of 1% trifluridine ophthalmic solution in dogs with experimentally induced recurrent ocular canine herpesvirus-1 infection. AB - OBJECTIVE To determine the effects of topical ocular application of 1% trifluridine ophthalmic solution in dogs with experimentally induced recurrent ocular canine herpesvirus-1 (CHV-1) infection. ANIMALS 10 specific pathogen-free Beagles. PROCEDURES 12 months prior to the beginning of the randomized, masked, placebo-controlled 30-day trial, latent ocular CHV-1 infection was experimentally induced in each dog by topical ocular inoculation of both eyes with a field strain of CHV-1. Recurrent ocular CHV-1 infection was induced by oral administration of prednisolone for 7 days (starting day 1). Starting on the fourth day of prednisolone administration, each dog received 1% trifluridine solution or artificial tears (placebo) topically in both eyes 6 times daily for 2 days and then 4 times daily for 12 days. Ophthalmic examinations were performed every 2 days, and ocular disease scores were calculated. Ocular samples for CHV-1 PCR assays and blood samples for clinicopathologic analyses and assessment of CHV 1 serum neutralization antibody titers were collected at predetermined intervals. RESULTS Conjunctivitis was clinically detected in all dogs by day 4. Compared with dogs receiving placebo, mean and total clinical ocular disease scores were significantly lower and median CHV-1 shedding duration was significantly shorter for the trifluridine-treated dogs. Both groups had increasing CHV-1 serum neutralization antibody titers over time, but no significant differences between groups were detected. Clinicopathologic findings were unremarkable throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE Topical ocular application of 1% trifluridine ophthalmic solution was well tolerated and effective at reducing disease scores and viral shedding duration in dogs with experimentally induced ocular CHV-1 infection, but may require frequent administration. PMID- 27668585 TI - Clinical effects of computed tomography-guided lumbosacral facet joint, transforaminal epidural, and translaminar epidural injections of methylprednisolone acetate in healthy dogs. AB - OBJECTIVE To determine clinical effects of CT-guided lumbosacral facet joint, transforaminal epidural, and translaminar epidural injections of methylprednisolone acetate in healthy dogs. ANIMALS 15 healthy Beagles. PROCEDURES Dogs were randomly assigned to 3 groups (5 dogs/group) and received a single CT-guided lumbosacral facet joint, transforaminal epidural, or translaminar epidural injection of methylprednisolone acetate (0.1 mg/kg). Contrast medium was injected prior to injection of methylprednisolone to verify needle placement. Neurologic examinations were performed 1, 3, 7, and 10 days after the injection. In dogs with neurologic abnormalities, a final neurologic examination was performed 24 days after the procedure. RESULTS Methylprednisolone injections were successfully performed in 14 of the 15 dogs. In 1 dog, vascular puncture occurred, and the methylprednisolone injection was not performed. No major or minor complications were identified during or immediately after the procedure, other than mild transient hyperthermia. During follow-up neurologic examinations, no motor, sensory, or postural deficits were identified, other than mild alterations in the patellar, withdrawal, cranial tibial, and perineal reflexes in some dogs. Overall, altered reflexes were observed in 11 of the 14 dogs, during 27 of 65 neurologic examinations. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that CT-guided lumbosacral facet joint, transforaminal epidural, and translaminar epidural injections of methylprednisolone acetate were associated with few complications in healthy dogs. However, the number of dogs evaluated was small, and additional studies are needed to assess clinical efficacy and safety of these procedures. PMID- 27668587 TI - Expression of T helper cell-associated inflammatory mediator mRNAs in cells of bronchoalveolar lavage fluid samples and oxygen concentration in arterial blood samples from healthy horses exposed to hyperbaric oxygen. AB - OBJECTIVE To evaluate the mRNA expression of T helper (Th)1, Th2, and Th17 cell associated inflammatory mediators in cells of bronchoalveolar lavage fluid samples collected from healthy horses exposed to hyperbaric oxygen (HBO) and to monitor blood oxygen concentration during and following HBO therapy. ANIMALS 8 healthy horses. PROCEDURES In a randomized controlled crossover design study, each horse was exposed (beginning day 1) to 100% oxygen at a maximum of 3 atmospheres absolute (304 kPa) daily for 10 days or ambient air at atmospheric pressure in the HBO chamber for an equivalent amount of time (control). Bronchoalveolar lavage fluid samples were collected on days 0 and 10. After validation of candidate reference genes, relative mRNA expressions of various innate inflammatory, Th1 cell-derived, Th2 cell-derived (including eotaxin-2), Th17 cell-derived, and regulatory cytokines were measured by quantitative PCR assays. For 3 horses, arterial blood samples were collected for blood gas analysis during a separate HBO session. RESULTS The optimal combination of reference genes was glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine ribosyltransferase, and ribosomal protein L32. Compared with day 0 findings, expression of eotaxin-2 mRNA was significantly lower (0.12-fold reduction) and the percentage of neutrophils in bronchoalveolar lavage fluid samples was significantly lower on day 10 when horses received HBO therapy. Values of Pao2 rapidly increased (> 800 mm Hg) but immediately decreased to pretreatment values when HBO sessions ended. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that HBO therapy does not increase mRNA expression of inflammatory cytokines, but reduces eotaxin-2 mRNA transcription. The Pao2 increase was transient with no cumulative effects of HBO. PMID- 27668588 TI - Isolation of endothelial colony-forming cells from blood samples collected from the jugular and cephalic veins of healthy adult horses. AB - OBJECTIVE To evaluate optimal isolation of endothelial colony-forming cells (ECFCs) from peripheral blood of horses. SAMPLE Jugular and cephalic venous blood samples from 17 adult horses. PROCEDURES Each blood sample was divided; isolation was performed with whole blood adherence (WBA) and density gradient centrifugation (DGC). Isolated cells were characterized by uptake of 1,1' dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein (DiI-Ac-LDL), vascular tubule formation, and expression of endothelial (CD34, CD105, vascular endothelial growth factor receptor-2, and von Willebrand factor) and hematopoietic (CD14) cell markers by use of indirect immunofluorescence assay (IFA) and flow cytometry. RESULTS Colonies with cobblestone morphology were isolated from 15 of 17 horses. Blood collected from the cephalic vein yielded colonies significantly more often (14/17 horses) than did blood collected from the jugular vein (8/17 horses). Of 14 cephalic blood samples with colonies, 13 were obtained with DGC and 8 with WBA. Of 8 jugular blood samples with colonies, 8 were obtained with DGC and 4 with WBA. Colony frequency (colonies per milliliter of blood) was significantly higher for cephalic blood samples and samples isolated with DGC. Cells formed vascular tubules, had uptake of DiI-Ac-LDL, and expressed endothelial markers by use of IFA and flow cytometry, which confirmed their identity as ECFCs. CONCLUSIONS AND CLINICAL RELEVANCE Maximum yield of ECFCs was obtained for blood samples collected from both the jugular and cephalic veins and use of DGC to isolate cells. Consistent yield of ECFCs from peripheral blood of horses will enable studies to evaluate diagnostic and therapeutic uses. PMID- 27668590 TI - Correction: Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs. PMID- 27668589 TI - Generation of pure cultures of autologous Schwann cells by use of biopsy specimens of the dorsal cutaneous branches of the cervical nerves of young adult dogs. AB - OBJECTIVE To identify an optimal technique for isolation, purification, and amplification of Schwann cells (SCs) from biopsy specimens of the dorsal cutaneous branches of the cervical nerves of dogs. SAMPLE Biopsy specimens of dorsal cervical cutaneous nerves from the cadavers of three 1- to 2-year-old dogs. PROCEDURES Nerve specimens were dissected, predegenerated, and dissociated to isolate single cells. After culture to enhance SC growth, cells were immunopurified by use of magnetic beads. Cell purity was evaluated by assessing expression of cell surface antigens p75 (to detect SCs) and CD90 (to detect fibroblasts). Effects of various concentrations of recombinant human glial growth factor 2 (rhGGF2) on SC proliferation were tested. Cell doubling time was assessed in SC cultures with selected concentrations of rhGGF2. RESULTS Mean +/- SD wet weight of nerve fascicles obtained from the biopsy specimens was 16.8 +/- 2.8 mg. A mean predegeneration period of 8.6 days yielded approximately 6,000 cells/mg of nerve tissue, and primary culture yielded 43,000 cells/mg of nerve tissue in a mean of 11 days, of which 39.9 +/- 9.1% expressed p75. Immunopurification with magnetic beads yielded a mean of 85.4 +/- 1.9% p75 positive cells. Two passages of subculture with 10MUM cytosine arabinoside further enhanced SC purity to a mean of 97.8 +/- 1.2% p75-positive cells. Finally, rhGGF2 supplementation at a range of 40 to 100 ng/mL increased the SC proliferation rate up to 3-fold. CONCLUSIONS AND CLINICAL RELEVANCE SCs could be cultured from biopsy specimens of dorsal cervical cutaneous nerves and purified and expanded to generate adequate numbers for autologous transplants to treat dogs with spinal cord and peripheral nerve injuries. PMID- 27668591 TI - Community belonging and sedentary behavior among First Nations adults in Canada: The moderating role of income. AB - This study examined how income and community belonging may interact to influence leisure sedentary behavior among Indigenous adults. Data were obtained from 1,304 First Nations adults who completed the Canadian Community Health Survey in 2012. Among average-income earners, a strong sense of belonging to local community was associated with less sedentary behavior, a finding also documented in the general population. Among low-income earners, a strong sense of belonging to local community was associated with more sedentary behavior, a finding that is novel in the literature. These associations remained significant after adjustment for sociodemographic covariates and mental and physical health, suggesting other factors are influencing this correlation. PMID- 27668592 TI - An urban American Indian health clinic's response to a community needs assessment. AB - Utilizing community-based methods, we assessed the behavioral and physical health needs of a Detroit metropolitan Indian health clinic. The project goal was to identify health service needs for urban American Indians/Alaska Natives and develop the infrastructure for culturally competent and integrative behavioral and physical health care. We conducted 38 semi-structured interviews and 12 focus groups with service providers and community members. Interview and focus group data indicated a need for 1) more culturally competent services and providers, 2) more specialized health services, and 3) more transportation options. We then report on the Indian health clinic's and community's accomplishments in response to the needs assessment. PMID- 27668593 TI - Identifying and understanding Indigenous ways of evaluating physical activity programs. AB - Indigenous evaluation frameworks have not been investigated in the context of American Indian and Alaska Native (AI/AN) physical activity programs, an important area given the relationship between effective physical activity programs and quality of life among these populations. To address this gap, staff members of AI/AN physical activity programs were interviewed to explore their understanding of and experiences with evaluation. Findings suggest that Indigenous evaluation is perceived as narrative and holistic, Indigenous knowledge is used in program decision making, though it is not always acknowledged as evaluation, and there is not a universally desired way to evaluate AI/AN physical activity programs. PMID- 27668594 TI - Native Generations: A campaign addressing infant mortality among American Indians and Alaska Natives in urban areas. AB - This study describes the development and evaluation of Native Generations, a campaign addressing high rates of infant mortality (IM) among American Indians and Alaska Natives (AI/ANs) in urban areas. Campaign development included reviews of literature and previous campaigns, an advisory council, and focus groups. Campaign messages are strength-based, encouraging AI/AN caregivers to utilize available Native-specific resources, including health care, support services, and programming as IM protective factors. The primary campaign material is an 11 minute video. Pilot survey data indicate the video may help increase awareness of IM and Native-specific resources, and increase connection to Native identity, culture, and community. PMID- 27668595 TI - [To the 80th anniversary of Lev Kisselev]. PMID- 27668596 TI - [A glimpse on Staphylococcus aureus translation machinery and its control]. AB - Staphylococcus aureus is a major opportunistic and versatile pathogen. Because the bacteria rapidly evolve multi-resistances towards antibiotics, there is an urgent need to find novel targets and alternative strategies to cure bacterial infections. Here, we provide a brief overview on the knowledge acquired on S. aureus ribosomes, which is one of the major antibiotic targets. We will show that subtle differences exist between the translation at the initiation step of Gram negative and Gram-positive bacteria although their ribosomes display a remarkable degree of resemblance. In addition, we will illustrate using specific examples the diversity of mechanisms controlling translation initiation in S. aureus that contribute to shape the expression of the virulence factors in a temporal and dynamic manner. PMID- 27668597 TI - [The true story and advantages of the famous Hepatitis B virus core particles: Outlook 2016]. AB - This review article is a continuation of the paper "Hepatitis B core particles as a universal display model: a structure-function basis for development" written by Pumpens P. and Grens E., ordered by Professor Lev Kisselev and published in FEBS Letters, 1999, 442, 1-6. The past 17 years have strengthened the paper's finding that the human hepatitis B virus core protein, along with other Hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. The core gene of the Hepadnaviridae genome encodes five partially collinear proteins. The most important of these is the HBV core protein p21, or HBc. It can self-assemble by forming viral HBc particles, but also plays a crucial role in the regulation of viral replication. Since 1986, the HBc protein has been one of the first and the most successful tools of the virus-like particle (VLP) technology. Later, the woodchuck hepatitis virus core protein (WHc) was also used as a VLP carrier. The Hepadnaviridae core proteins remain favourite VLP candidates for the knowledge based design of future vaccines, gene therapy vectors, specifically targeted nanocontainers, and other modern nanotechnological tools for prospective medical use. PMID- 27668599 TI - [Glial cell line-derived neurotrophic factor family ligands and their therapeutic potential]. AB - Four glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) have been characterized: GDNF, neurturin (NRTN), artemin (ARTN) and persephin (PSPN). These proteins support and restore multiple neuronal populations such as dopaminergic, sensory, motor, hippocampal, basal forebrain, enteric, sympathetic and parasympathetic neurons. Therefore, GFLs attracted significant attention as a potential cure for the diseases caused by neuronal injury and degeneration. Results of multiple experiments indicate that GFLs can alleviate behavioral symptoms and restore affected neurons in animal models of several neurological disorders including, among others, Parkinson's disease (PD). During the last decade, GDNF protein and NRTN gene therapy have been tested in several clinical trials in patients with PD. Although the results of phase I clinical trials were positive, phase II clinical trials failed to reach primary end-points. Poor pharmacokinetic properties of GFLs (inability to penetrate tissues barriers, high affinity for extracellular matrix, etc.) could contribute to the absence of clear clinical benefits of these proteins for the patients. The purpose of this paper was to review therapeutic potential of GFLs and discuss possibilities to overcome difficulties associated with pharmacokinetic properties and delivery of GFLs to target neurons. PMID- 27668598 TI - [S100A4, a link between metastasis and inflammation]. AB - Chronic inflammation is acknowledged to be a hallmark of neoplasia - both in cancer initiation and metastasis progression. Here we summarise data suggesting that S100A4 is a trigger of the cascade events that establish an inflammatory milieu and provide a potent flame for primary tumour growth and especially for its metastatic dissemination. The S100A4 protein belongs to the S100 superfamily of small Ca^(2+)-binding proteins. Well established function of S100A4 is associated with induction and promotion of tumour metastasis. However, this protein is also involved in the pathogenesis of major human non-communicable diseases (NCD), such as autoimmune diseases, fibrosis, and other disorders. Therefore, we suggest that S100A4 is a common pro-inflammatory factor involved in the pathogenesis of diverse NCD including cancer. PMID- 27668600 TI - [Inhibiting the pro-tumor and transcription factor FACT: Mechanisms]. AB - Conventional antitumor therapy is often complicated by the emergence of the so called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity. Curaxins simultaneously affect at least three key molecular cascades involved in tumor development, including the p53, NF-kappaB, and HSF1 metabolic pathways. In addition, studies of some curaxins indicate that they can inhibit the transcriptional induction of the genes for matrix metalloproteinases 1 and 8 (MMP1 and MMP8); the PI3K/AKT/mTOR signaling cascades; cIAP-1 (apoptosis protein 1) inhibitor activity; topoisomerase II; and a number of oncogenes, such as c-MYC and others. In vivo experiments have shown that the CSC population increases on gemcitabine monotherapy and is reduced on treatment with curaxin CBL0137. The data support the prospective use of FACT inhibitors as new anticancer drugs with multiple effects on cell metabolism. PMID- 27668601 TI - [Genome: Origins and evolution of the term]. AB - The appearance of a new scientific term is a significant event in the human cognitive process and the result of the realization of the separateness of an object or a phenomenon. Our article concentrates on the origins of basic genetic terms, such as genetics, gene, genotype, genome, gene pool, and genomics. We propose using the term karyogenomics for the special direction of genomics related to the study of the organization and evolution of eukaryotic genomes by means of modern chromosome analysis, as well as by full genome sequencing. PMID- 27668602 TI - [Novel human DNA viruses and their putative associations with human diseases]. AB - In this review, we described human small DNA viruses discovered on the cusp of the 20th and 21st centuries as a result of cutting-edge technologies established in molecular biology. The problems of obtaining an evidence of the etiological role of new viruses in human diseases have been considered. PMID- 27668603 TI - [Role of DNA-dependent protein kinase in the HIV-1 replication cycle]. AB - Human immunodeficiency virus type 1 (HIV-1) is among the best-studied viruses, but some aspects of HIV-1 biology remain obscure. The role of cell proteins in virus replication raises especially many questions. One of the proteins is DNA dependent protein kinase (DNA-PK), which performs crucially important functions in the human body. DNA-PK is known to influence at least two stages in the HIV-1 life cycle, the integration of viral genome in cell DNA and transcription of the integrated provirus. Many details regarding this influence remain unresolved. The review summarizes the known data on the DNA-PK role in the HIV-1 life cycle and its influence on the replication of other members of the family Retroviridae. In the beginning of this review there is a short explanation of the DNA-PK cellular functions that are especially important for understanding its role in the HIV-1 replication. PMID- 27668604 TI - [Poly(ADP-Ribose) polymerase 1 as a key regulator of DNA repair]. AB - Poly(ADP-ribosyl)ation (PARylation) of proteins is one of the immediate cell responses to DNA damage and is catalyzed by poly(ADP-ribose) polymerases (PARPs). When bound to damaged DNA, some members of the PARP family are activated and use NAD^(+) as a source of ADP to catalyze synthesis of poly(ADP-ribose) (PAR) covalently attached to a target protein. PAR synthesis is considered as a mechanism that provides a local signal of DNA damage and modulates protein functions in response to genotoxic agents. PARP1 is the best-studied protein of the PARP family and is widely known as a regulator of repair of damaged bases and single-strand nicks. Data are accumulating that PARP1 is additionally involved in double-strand break repair and nucleotide excision repair. The review summarizes the literature data on the role that PARP1 and PARylation play in DNA repair and particularly in base excision repair; original data obtained in our lab are considered in more detail. PMID- 27668605 TI - [Multilocus analysis of the association of polymorphic variants of inflammation genes with ischemic stroke in Russians]. AB - Carriage frequencies of alleles and genotypes of polymorphic loci of inflammation genes (49A>G CTLA4, 41G>A and 87C>T PDE4D, -590C>T IL4, -308A>G TNF, 252G>A LTA, 874A>T IFNG, -509S>T, 869T>C and 915G>C TGFB1) were determined in a sample of 200 patients diagnosed with ischemic stroke and in the control group similar in gender and age (146 individuals), all ethnic Russians. The positive association of the allele PDE4D*87C (r = 0.028) and genotype TGFB1*-509T/T (r = 0.02) carriage with ischemic stroke was shown. The association of the disease with the carriage of the allele PDE4D*41A (r = 0.009) in individuals under the age of 60 and with carriage of the allele IFNG*874T (r = 0.02) in individuals older than 60 was observed among the subgroups of patients stratified by age when they suffered the stroke compared to a control group of the same age. In subgroups stratified by gender, carriage of the genotype TGFB1*915G/G (r = 0.0015) was identified as a risk factor in male patients, while no significant differences between female patients and healthy women were observed. Multilocus analysis was undertaken to search for the association of several combinations of studied gene variants with ischemic stroke. The polymorphic locus-174G>C of the IL6 gene, for which an association with the disease was previously demonstrated, was also included in this analysis. The disease-predisposing biallelic combinations include the IL6* 174G, PDE4D*87C, TGFB1*-509T and TGFB1*915G alleles. In the subgroups stratified by gender, the allelic combinations mainly include the similar risk alleles as in the total group, while between the subgroups stratified by age (patients who suffered the first stroke at the age of 18 and no older than 60 years and older than 60 years), greater differences were observed. However, a new risk allele, LTA*252G, was identified in combination with PDE4D*41A in women. These findings demonstrate the important role of inflammation in ischemic stroke. The identified single and combined markers may be used further to determine an individual risk for ischemic stroke. PMID- 27668606 TI - [Lessons from cyanobacterial transcriptomics: Universal genes and triggers of stress responses]. AB - A systemic transcriptome analysis of the cyanobacterium Synechocystis sp. PCC 6803 revealed a number of genes whose transcription is induced in response to almost all abiotic stresses (heat shock, salt stress, osmotic stress, oxidative stress, changes in light intensity or spectral composition, and changes in the redox potential of electron transport chain (ETC) components). Heat shock protein (HSP) genes were induced by all types of stress, forming a group of genes that universally react to various changes in the environment. Reactive oxygen species (ROS), including H2O2 in particular, and changes in the redox potential of components of the photosynthetic ETC were assumed to function as universal triggers of stress responses in cyanobacteria. PMID- 27668607 TI - [Ratio of transcription factor PHF10 splice variants in lymphocytes as a molecular marker of Parkinson's disease]. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder and causes degeneration of dopaminergic neurons in the nigrostriatal system of the brain. PHF10 is one of the most important regulatory subunits of the SWI/SNF chromatin-remodeling protein complex, which controls the gene function and chromatin state in neurons. Two alternative RHF10 isoforms, PHF10-P and PHF10-S, replace each other in the complex to change the target gene pattern. Expression of the PHF10-P and PHF10-S transcripts in the nigrostriatal system and their ratio in blood lymphocytes were found to change in a mouse model of early clinical stage of PD as compared with control mice. Changes in PHF10-S level were also observed in peripheral blood lymphocytes from patients with early clinical stage of PD. A ratio of the PHF10-P and PHF10-S transcripts in peripheral blood cells was assumed to provide a potential marker of early stage PD. PMID- 27668608 TI - [Inhibition of the expression of proteasomal genes Saccharomyces cerevisiae by artificial transcriptional repressor]. AB - 26S proteasome is an ATP-dependent protease complex that takes part in cell homeostasis maintenance by the selective degradation of regulatory and damaged proteins. The proteasomal genes expression in Saccharomyces cerevisiae yeast is coordinately regulated by the system, which consists of the Rpn4 transcription factor and its binding site, called PACE. The ability to modulate proteasomal activity by changing the expression of its genes is an essential tool that can be used in fundamental studies devoted to the mechanisms of proteasome dependent cell processes, as well as in applied research for developing strategies to correct proteasome activity in some pathological processes. In this work, we present a detailed description of our SaxBricks method that allows one to construct DNA-binding domains with custom specificity from nucleotide- specific TAL domains. Having applied the SaxBricks method, we created a modular transcriptional repressor for Rpn4-dependent genes that effectively suppresses the expression of proteasomal genes. PMID- 27668609 TI - [The role of Piwi nuclear localization in the differentiation and proliferation of germline stem cells]. AB - The Piwi protein and its orthologs are considered as the key components of the piRNA machinery implicated in transcriptional silencing of transposons. Nere, we show that nuclear localization of the Piwi protein is required not only for transposon repression, but also for proper differentiation of germline stem cells (GSCs). piwi^(Nt) mutation that causes loss of nuclear Piwi and its retention in the cytoplasm leads to the accumulation of undifferentiated GSC-like cells. The analysis of piwi^(Nt) mutation in combination with a bam gene mutation blocking GSC differentiation shows that the loss of nuclear Piwi decreases GSC proliferation rate. This is accompanied by the accumulation of DNA double-strand breaks in GSCs that may be caused by transposition events. Here, for the first time a set of transposons repressed by Piwi in GSCs and surrounding niche cells has been identified. The present study together with our previous data show that nuclear and cytoplasmic Piwi can regulate different stages of the functioning of germinal cells: cytoplasmic Piwi is sufficient to maintain GSCs, while nuclear Piwi localization is necessary for their proper proliferation and differentiation. PMID- 27668610 TI - Medical Informatics as a Set of Human Sciences? Why Not? PMID- 27668611 TI - Advanced Communications in Health Care. PMID- 27668612 TI - Integrated Advanced Medical Information Systems (IAIMS): Payoffs and Problems. AB - IAIMS (Integrated Advanced Information Management Systems) is an initiative to improve the access to information needed to provide patient care, health-oriented education, biomedical research, and management of large medical center environments. This paper will review the goals, history, and accomplishments of the IAIMS initiative. Shortcomings and frustrations, lessons learned, and the future of such initiatives will also be discussed. PMID- 27668613 TI - Medical Image Processing in an Era of High-Performance Computing. AB - Advanced radiology practices are already benefiting from powerful and increasingly more economical computing and networking facilities. Medical image processing methods have improved dramatically over the past five years, with sophisticated 3D display, visualization and analysis techniques allowing increased integration of multiple modalities of imaging, flexible environments for imaging analysis, and PACS (picture archiving and communication systems) for ease of transmission and retrieval. Emerging directions involve teleradiology and telesurgery virtual reality applications, the development of new image database techniques, and the building of large visual databases like that of the Visible Human Project. Challenging problems of image segmentation, registration, and multimodal image fusion are still with us. Building dynamic, flexible electronic atlases will have a profound effect on the understanding of structure and function from the level of cellular physiology to gross anatomy, but requires the development of new techniques of visual knowledge representation and more standardized ways of defining the conceptual and linguistic constructs of visual objects in biomedicine, for linkage to medical records, research results, and educational materials. Methods for reasoning with visual information in the context of multimedia information systems present an inviting challenge to the upcoming generation of researchers in medical informatics. PMID- 27668614 TI - Communication in Health Care. AB - For routine communication, care providers still rely on paper documents and paper mail. At present, new technologies are emerging that have considerable potential for improving communication in health care. This paper reviews existing communication problems, and discusses electronic communication techniques that are gradually replacing paper-based communication. PMID- 27668615 TI - Next Generation - Health Professional Workstations. PMID- 27668616 TI - Nursing Informatics: State of the Science. AB - Nursing informatics is a combination of computer science, information science and nursing science designed to support the practice and delivery of patient care. Using the informatics model of data, information and knowledge, the nature of automated systems to support clinicians in their delivery of high-quality care are described from their inception to their current state, and the importance of research to advance the state of nursing knowledge are emphasized. The evolution of clinical care systems and nursing management systems are viewed,as is the progress of the scientific work relative to nursing informatics. Milestones in the advancing state of the science are identified and the conclusion is drawn that although nursing informatics has evolved, much scientifically based work remains. Key nursing informatics resources identified in the paper support this conclusion about what remains to be accomplished. PMID- 27668617 TI - Hospital Information Systems: A Review in Perspective. AB - The demand for information for health care is increasing exponentially in volume, content and the number and geographical distribution of users. Most HIS systems commercially available today are based on designs and philosophies of the 1970s. Even though new technology has improved these systems' performance, to meet current demands, concepts must be shifted from the paper-driven system to an electronic system in which the patient is the focus. We need a merger of the functionality of existing systems along with new functionalities and a computer based patient record. These new health care information system must have no boundaries; data collection must permeate all locations at which a patient receives care, and seamless linkages must connect all individuals who contribute to that patient's care. Even though systems are being designed today to meet these expanded informational requirements, we will not see such systems in use before the next century. PMID- 27668619 TI - Twenty Years Medical Informatics Education at Heidelberg/Heilbronn: Evolution of a Specialized Curriculum. AB - The medical informatics curriculum at University of Heidelberg/School of Technology Heilbronn started in 1972 as a specialized university curriculum. In this paper, we report on 20 years of experience and the evolution of this educational approach with respect to structure and content of the curriculum. We emphasize that this evolution parallels the development of medical informatics to a medical discipline in its own right, with distinct application domains and specific methodological approaches. Based on our experience and on recommendations from the national and international community, we describe and discuss the features of the curriculum. PMID- 27668618 TI - The Harvard-MIT-NEMC Research Training Program in Medical Informatics. AB - The Harvard-MIT-NEMC Research Training Program in Medical Informatics brings together five separate research groups to provide a diversified training experience in Boston with sponsorship by the National Library of Medicine. This program offers predoctoral and postdoctoral programs, supplemented by many opportunities for collegial exchange and interaction among the groups. PMID- 27668620 TI - Graduate Program in Medical Informatics at the University of Utah. AB - The graduate student program in medical informatics at the University of Utah described in this paper comprises a Master of Science degree (since 1976) and a Ph.D. degree (since 1962). The average program length is 2 years for M.Sc. and 3 5 years for Ph.D. The aims of the program are to prepare graduates for careers in medical informatics in academic, hospital or industrial settings. There are several different courses of study, or tracks, within the department ranging from Expert Systems, Genetic Epidemiology, Health Care Quality, Hospital Information Systems, Medical Imaging, Medical Physics, to an intensive oneyear M.Sc. degree course for physicians. After the first three quarters the students are required to take a qualifying examination in which they qualify for a Masters or Ph.D. degree. The program covers the total spectrum of medical informatics. About 10 students are admitted each year. There are 14 full-time faculty and 9 adjunct faculty. The total number of graduates is 151. PMID- 27668621 TI - Health and Clinical Management. PMID- 27668623 TI - Information Systems. PMID- 27668622 TI - Computer-Based Patient Records. PMID- 27668624 TI - Image and Signal Processing. PMID- 27668625 TI - Decision-Support Systems. PMID- 27668626 TI - Knowledge Processing. PMID- 27668627 TI - Education. PMID- 27668629 TI - Better Information for Better Healthcare. PMID- 27668628 TI - Research and Development Programmes of The European Union in Health Telematics: A Leverage for Convergence. PMID- 27668630 TI - Overview of diabetic macular edema. AB - Diabetes mellitus (DM) is a rapidly growing epidemic in the United States, and it is expected to affect 592 million individuals within the next 20 years. Diabetic retinopathy (DR) and diabetic macular edema (DME) are the 2 most common ophthalmic complications of DM. DR is the leading cause of blindness among working-age adults around the world, and development of DR is tied to DM disease duration. With the only identifier of early markers of DR being a complete ophthalmic exam, early signs of the disease are asymptomatic. Yearly, or at least every other year, ophthalmic exams are recommended for all patients with DM; but often, individuals with DM have not undergone screening exams and do not have regular eye exams until vision loss has occurred. With spending estimates of $490 million to treat the vision complications of DM, it is clear that DR and DME impose a substantial burden for patients, caregivers, and healthcare systems. PMID- 27668631 TI - Current approaches to the management of diabetic macular edema. AB - Three modalities have a role in the primary management of diabetic macular edema (DME): laser photocoagulation, intravitreal vascular endothelial growth factor (VEGF) inhibitors, and intravitreal corticosteroid implants. Intravitreal VEGF inhibitors are most commonly used for center-involved DME, but laser photocoagulation and intravitreal corticosteroids also have an important role in DME management. Until recently, the selection of a VEGF inhibitor for a patient was complicated by a lack of comparative data and a much lower cost for bevacizumab compared with other agents. Two-year results of the landmark head-to head Protocol T trial will inform treatment selection for ophthalmologists and formulary decisions for managed care organizations. The study found that patients with better baseline visual acuity benefited from aflibercept, bevacizumab, or ranibizumab. However, aflibercept and ranibizumab were more effective than bevacizumab for patients with worse baseline visual acuity. A higher rate of nonfatal stroke and vascular death with ranibizumab in the Protocol T trial has raised concern in the community and needs to be investigated further. Emerging drugs for DME include VEGF inhibitors with less-frequent dosing intervals, and new agents that target other pathologic processes that contribute to vascular leakage and angiogenesis in DME. PMID- 27668632 TI - Managed care implications of diabetic macular edema. AB - Diabetic retinopathy (DR) is both the leading cause of blindness among adults aged 20 to 74 in the United States, and the leading ocular complication associated with diabetes mellitus (DM). An estimated 4.4% of adults with DM over 40 years of age have the more advanced form of DR: diabetic macular edema (DME), which significantly increases the risk of blindness. Medical costs for Medicare patients with DME are a third higher than for patients without DME. The majority of these costs stem from other DM-related complications, as DME is a marker for poorly controlled DM overall. Commercially insured patients with DME incur direct and indirect costs up to 75% higher than for those with DR without DME. Early detection, treatment, and improved glycemic control can limit the onset or progression of microvascular complications of DR, including DME, resulting in significant savings for payers. However, there are significant gaps in adherence to national guidelines regarding DM control and early identification of DR. In addition, patients face several barriers to screening. Improving screening for and management of early DR could decrease progression to DME, which would provide significant savings for payers, as well as improve the quality of care and outcomes for patients with DM. Managed care organizations and employers should also consider the cost-effectiveness of currently available treatments for DME: focal laser photocoagulation, vascular endothelial growth factor inhibitors, and intravitreal corticosteroid injections and implants, in their formulary design; they should also identify opportunities to improve patient adherence to treatment. PMID- 27668633 TI - Expanding Advocacy for Head Trauma Vision Research Funding. AB - In this article, we explore the roles of media, research, and advocacy in education and research funding. All three have played critical roles in advancing our understanding of eye, vision, and brain injuries in sports and in the military. PMID- 27668636 TI - Descemet's Membrane Detachment with Schisis Induced by Phacoemulsification. AB - PURPOSE: To describe a case of Descemet's membrane detachment and schisis (Descemet's membrane separated into multiple layers) with confirmation by high definition anterior segment optical coherence tomography (AS-OCT) after phacoemulsification and intraocular lens implantation. CASE REPORT: A 72-year-old woman presented with persistent corneal edema after phacoemulsification. She was diagnosed with herpes simplex keratitis and had been unsuccessfully treated for 60 days in her local hospital. Slit-lamp examination revealed moderate conjunctival injection, disciform-like stromal edema, and diffuse superficial punctate epithelial erosions. Descemet's membrane schisis and detachment with an interlayer tear were verified by high-definition AS-OCT. After 2 weeks of medication with topical 0.1% fluorometholone eye drops four times daily together with 3% ofloxacin eye ointment twice daily, Descemet's membrane was reattached with complete resolution of conjunctival injection, corneal edema, and epithelial erosions. CONCLUSIONS: This is a report of Descemet's membrane schisis in vivo that is documented and confirmed by high-definition AS-OCT. Descemet's membrane detachment and schisis caused by phacoemulsification can be misdiagnosed as herpetic keratitis due to stromal edema and epithelial erosion. Topical steroid and lubrication may help reattach Descemet's membrane to its original position. PMID- 27668635 TI - Assessment of Lower Tear Meniscus. AB - PURPOSE: To evaluate the applicability of the fourth-generation OCULUS keratograph in measuring lower tear meniscus height. METHODS: Seventy cases (140 eyes) with dry eye disease and 37 controls (74 eyes) were enrolled. Tear breakup time (TBUT), Schirmer test I, and corneal fluorescein staining were examined. The images of lower tear meniscus were obtained by OCULUS keratograph. The tear meniscus height was measured and its correlation with traditional tear film diagnostic tests were analyzed. RESULTS: Using the hyper-reflective lines, the height of the tear meniscus was measured using the images of the OCULUS keratograph. For the inter-individual variation, the intraclass correlation coefficients and coefficient of variation values were 0.914 and 16.4%, respectively. For the intra-individual variation, the intraclass correlation coefficients and coefficient of variation values were 0.939 and 15.9%, respectively. The interobserver reproducibility and the intraobserver repeatability were for the control only. The average tear meniscus height value in dry eye disease group was 0.22 (0.19-0.24) mm, being significantly lower compared with 0.29 (0.26-0.34) mm in the control group (p<0.001). Tear meniscus height value had significantly correlation with TBUT and Schirmer test I (r=0.619 and 0.626, both p<0.001). The measurement of lower tear meniscus by OCULUS had lower individual variability and better repeatability. CONCLUSIONS: OCULUS keratograph is a quick, noninvasive, and reliable method to measure lower tear meniscus, whose value has a significant correlation with traditional dry eye disease diagnostic tests. PMID- 27668637 TI - Effect of Pupil Size on Wavefront Refraction during Orthokeratology. AB - PURPOSE: It has been hypothesized that central and peripheral refraction, in eyes treated with myopic overnight orthokeratology, might vary with changes in pupil diameter. The aim of this work was to evaluate the axial and peripheral refraction and optical quality after orthokeratology, using ray tracing software for different pupil sizes. METHODS: Zemax-EE was used to generate a series of 29 semi-customized model eyes based on the corneal topography changes from 29 patients who had undergone myopic orthokeratology. Wavefront refraction in the central 80 degrees of the visual field was calculated using three different quality metrics criteria: Paraxial curvature matching, minimum root mean square error (minRMS), and the Through Focus Visual Strehl of the Modulation Transfer Function (VSMTF), for 3- and 6-mm pupil diameters. RESULTS: The three metrics predicted significantly different values for foveal and peripheral refractions. Compared with the Paraxial criteria, the other two metrics predicted more myopic refractions on- and off-axis. Interestingly, the VSMTF predicts only a marginal myopic shift in the axial refraction as the pupil changes from 3 to 6 mm. For peripheral refraction, minRMS and VSMTF metric criteria predicted a higher exposure to peripheral defocus as the pupil increases from 3 to 6 mm. CONCLUSIONS: The results suggest that the supposed effect of myopic control produced by ortho-k treatments might be dependent on pupil size. Although the foveal refractive error does not seem to change appreciably with the increase in pupil diameter (VSMTF criteria), the high levels of positive spherical aberration will lead to a degradation of lower spatial frequencies, that is more significant under low illumination levels. PMID- 27668634 TI - Validation of Macular Choroidal Thickness Measurements from Automated SD-OCT Image Segmentation. AB - PURPOSE: Spectral domain optical coherence tomography (SD-OCT) imaging permits in vivo visualization of the choroid with micron-level resolution over wide areas and is of interest for studies of ocular growth and myopia control. We evaluated the speed, repeatability, and accuracy of a new image segmentation method to quantify choroid thickness compared to manual segmentation. METHODS: Two macular volumetric scans (25 * 30 degrees ) were taken from 30 eyes of 30 young adult subjects in two sessions, 1 hour apart. A single rater manually delineated choroid thickness as the distance between Bruch's membrane and sclera across three B-scans (foveal, inferior, and superior-most scan locations). Manual segmentation was compared to an automated method based on graph theory, dynamic programming, and wavelet-based texture analysis. Segmentation performance comparisons included processing speed, choroid thickness measurements across the foveal horizontal midline, and measurement repeatability (95% limits of agreement (LoA)). RESULTS: Subjects were healthy young adults (n = 30; 24 +/- 2 years; mean +/- SD; 63% female) with spherical equivalent refractive error of -3.46 +/- 2.69D (range: +2.62 to -8.50D). Manual segmentation took 200 times longer than automated segmentation (780 vs. 4 seconds). Mean choroid thickness at the foveal center was 263 +/- 24 MUm (manual) and 259 +/- 23 MUm (automated), and this difference was not significant (p = 0.10). Regional segmentation errors across the foveal horizontal midline (+/-15 degrees ) were <=9 MUm (median) except for nasal-most regions closest to the nasal peripapillary margin-15 degrees (19 MUm) and 12 degrees (16 MUm) from the foveal center. Repeatability of choroidal thickness measurements had similar repeatability between segmentation methods (manual LoA: +/-15 MUm; automated LoA: +/-14 MUm). CONCLUSIONS: Automated segmentation of SD-OCT data by graph theory and dynamic programming is a fast, accurate, and reliable method to delineate the choroid. This approach will facilitate longitudinal studies evaluating changes in choroid thickness in response to novel optical corrections and in ocular disease. PMID- 27668638 TI - Methods to Develop the Eye-tem Bank to Measure Ophthalmic Quality of Life. AB - PURPOSE: There is an increasing demand for high-standard, comprehensive, and reliable patient-reported outcome (PRO) instruments in all the disciplines of health care including in ophthalmology and optometry. Over the past two decades, a plethora of PRO instruments have been developed to assess the impact of eye diseases and their treatments. Despite this large number of instruments, significant shortcomings exist for the measurement of ophthalmic quality of life (QoL). Most PRO instruments are short-form instruments designed for clinical use, but this limits their content coverage often poorly targeting any study population other than that which they were developed for. Also, existing instruments are static paper and pencil based and unable to be updated easily leading to outdated and irrelevant item content. Scores obtained from different PRO instruments may not be directly comparable. These shortcomings can be addressed using item banking implemented with computer-adaptive testing (CAT). Therefore, we designed a multicenter project (The Eye-tem Bank project) to develop and validate such PROs to enable comprehensive measurement of ophthalmic QoL in eye diseases. METHODS: Development of the Eye-tem Bank follows four phases: Phase I, Content Development; Phase II, Pilot Testing and Item Calibration; Phase III, Validation; and Phase IV, Evaluation. CONCLUSIONS/DISCUSSION: This project will deliver technologically advanced comprehensive QoL PROs in the form of item banking implemented via a CAT system in eye diseases. Here, we present a detailed methodological framework of this project. PMID- 27668640 TI - Evaluation of the SVOne Handheld Autorefractor in a Pediatric Population. AB - PURPOSE: The SVOne is a portable, Hartmann-Shack wavefront aberrometer, which can be attached to a smartphone to determine the refractive error of the eye objectively. Previous results have shown the device to provide measurements equivalent to those of standard clinical techniques in young, healthy adults. The aim of the present study was to compare the findings of the SVOne with retinoscopy, subjective refraction, and two commercially available autorefractors (Retinomax-3 and WAM-5500) in a pediatric population. METHOD: The refractive error of the right eye was assessed both without and with cycloplegia in 40 visually normal children between 5 and 17 years of age (mean age = 11.3 years) using the five techniques described above. Further, to assess repeatability of the instruments, the entire procedure was repeated in a subgroup of five subjects. All data were analyzed in terms of power vectors (M, J0, and J45). RESULTS: No significant difference was observed between the mean values of M (spherical equivalent) for the different techniques. Retinoscopy showed the best agreement with subjective refraction, both without and with cycloplegia, followed by the open-field WAM-5500. The most repeatable procedures, when measured without and with cycloplegia, were the WAM-5500 and retinoscopy, respectively. Measurements with the SVOne showed a decline in repeatability under cycloplegia. CONCLUSIONS: The results indicate that the SVOne provides measurements of refractive error in a normal, pediatric population that are not significantly different from other subjective and objective procedures. Accurate alignment along the visual axis, especially when measuring through a dilated pupil, is critical. This instrument is valuable for vision screenings, for examinations taking place outside the clinical office, and a starting point for the refractive assessment. PMID- 27668639 TI - Fundus Autofluorescence in Age-related Macular Degeneration. AB - : Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID- 27668643 TI - Co-transfer of blaNDM-5 and mcr-1 by an IncX3-X4 hybrid plasmid in Escherichia coli. AB - Carbapenem and colistin are the last-resort antibiotics used for treating multidrug-resistant Gram-negative pathogens. Here, we report, for the first time, co-transfer of resistance to both classes of antibiotics by a mobile IncX3-X4 hybrid plasmid in an Escherichia coli isolate. Spread of such a plasmid is of great concern for clinical therapy, and heightened efforts are needed to control its dissemination. PMID- 27668641 TI - Academic Difficulty and Vision Symptoms in Children with Concussion. AB - PURPOSE: Academic difficulty is reported in children with prolonged post concussive symptoms. Despite growing evidence that vestibular-ocular and vision specific dysfunction are common in children after concussion, vision is rarely mentioned in return-to-learn protocols. The purpose of this project was to evaluate a cohort of children with prolonged post-concussive symptoms to determine if vision symptoms are associated with those reporting academic difficulty. METHODS: Data were obtained from the Children's of Alabama Concussion Clinic REDCap dataset from the period January 2007 to October 2013. From this dataset of 1033 concussion events, a cohort of 276 children aged 5 to 18 years with three or more concussion-related symptoms present for 10 days or more was identified. A cross-sectional cohort study was undertaken to evaluate the association of concussion symptoms, SCAT2 scores, and demographic and concussion severity markers to reported educational difficulty among children with prolonged post-concussive symptoms. Univariate and multivariate logistic regression techniques were used to model the association of reported educational difficulty to self-reported vision abnormalities. RESULTS: Mean age was 13.8 years. Median time since the concussive event was 21 days, with 33% (95/276) reporting their concussion more than 30 days before data collection. Academic difficulty was reported by 29% (79/270) and vision abnormalities in 46% (128/274). After model reduction, vision symptoms (OR 2.17, 95% CI 1.02, 4.62), hearing disturbance (OR 2.39, 95% CI 1.06, 5.36), and concentration difficulty (OR 21.62, 95% CI 9.50, 44.47) remained associated with academic difficulty. For those with symptoms 30 days or more after concussion, only vision (OR 3.15, 95% CI 1.06, 9.38) and concentration difficulty (OR 15.33, 95% CI 4.99, 47.05) remained statistically significant. CONCLUSIONS: Vision problems were commonly reported in children with concussions and were independently associated with those reporting academic difficulty. Comprehensive vision assessment should be considered in children reporting academic difficulty and in the development of return-to-learn protocols. PMID- 27668644 TI - The renin-angiotensin-aldosterone system (RAAS) - physiology and molecular mechanisms of functioning. AB - Secretion of renin juxtaglomerular cells into bloodstream initiates activation of an enzymatic-hormonal cascade known as the RAAS (renin - angiotensin - aldosterone system). As a result, blood pressure is increased by the means several interrelated mechanisms. Mechanism of Zjednoczoaction of this system has been known for decades, but a few previously unknown components were recently added, such as ACE-2 and Ang(1-7), and their role often seems to be opposite to that of the conventional components. Local tissue systems also have important biological functions. They operate largely independently of the systemic activity, and their activity is observed primarily in the kidney, heart, in blood vessels, adrenal gland and nervous system. Angiotensin-2 (Ang-2), the main RAAS effector, has a wide scope of action, and thus abnormalities in its functioning have many consequences. Excessive activation is accompanied by chronic inflammation, as Ang-2 stimulates inflammatory mediators. As a result, degenerative processes and atherosclerosis are initiated. RAAS imbalance is associated with the most common diseases of civilization, such as cardio-vascular diseases, diabetes, kidney diseases, preeclampsia, osteoporosis and even neurodegenerative diseases. Many of these pathological processes are attributed to the excessive activation of tissue RA system. Therapeutic strategies based on inhibition of the RAAS are commonly used mainly in the treatment of hypertension and other cardiovascular disorders. The benefits of this class of drugs is primarily a decrease in blood pressure, but also the suppression of inflammatory processes and other pathological phenomena resulting from excessive activation of the RAAS. For that reason, some consider to use RAAS inhibitors in other diseases, e.g. Parkinson's disease. Further studies give hope for the improvement of RAAS inhibitor therapy and the development of new therapeutic strategies. PMID- 27668645 TI - Growth hormone deficiency in children and young adults. AB - Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit. PMID- 27668646 TI - The role of 6-phosphofructo-2-kinase (PFK-2)/fructose 2,6-bisphosphatase (FBPase 2) in metabolic reprogramming of cancer cells. AB - The high rate of glucose breakdown is the fingerprint of cancer. Increased glycolysis allows tumour cells to fulfil their high energetic and biosynthetic demands. Interestingly, however, rather than metabolizing glucose in the oxidative phosphorylation pathway, cancer cells generally use glucose for aerobic glycolysis. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental forms of metabolic reprogramming during cancerogenesis. Changes in the rate of glycolytic activity of cancer cells are caused mainly by the increased expression of glycolytic enzymes as a consequence of activation of oncogenes or loss of tumour suppressors. In addition, the hypoxic tumour environment also triggers upregulation of a series of genes involved in glucose metabolism. Among the metabolic enzymes that are modulated by these factors in cancer cells are the 6-phosphofructo 2-kinase/fructose 2,6 bisphosphatases (PFKFBs), a family of bifunctional enzymes that control the levels of fructose 2,6-bisphosphate (Fru-2,6-P2), an essential activator of the glycolytic flux. Fru-2,6-P2 strongly activates glucose breakdown in glycolysis through allosteric modulation of the rate-limiting enzyme of glycolysis, phosphofructokinase-1 (PFK-1). Thus far, many studies have reported a correlation between aberrant PFKFB expression level and the grade of tumour aggressiveness, which directly indicates that these enzymes may play a crucial role in cancerogenesis. The objective of this review is to highlight the recent studies on aberrant expression of PFKFBs and its influence on cancer progression. PMID- 27668647 TI - The role of extracellular vesicles in parasite-host interaction. AB - Zewnatrzkomorkowe pecherzyki blonowe (EVs, extracellular vesicles), poczatkowo uwazane za elementy zniszczonych komorek, okazaly sie niezwykle istotnym sposobem przekazywania informacji miedzy komorkami, bez ich bezposredniego kontaktu. Ze wzgledu na powszechne wystepowanie EVs w komorkach organizmow zarowno jedno-, jak i wielokomorkowych nalezacych do roznych grup systematycznych oraz ze wzgledu na pelniona role w komunikacji miedzykomorkowej staly sie przedmiotem licznych badan i dyskusji. EVs sa uwalniane przez komorki prokariotyczne, jak i eukariotyczne, zarowno w warunkach in vivo, jak i in vitro. Chociaz uzyskiwane frakcje EVs sa zwykle mieszanina roznorodnych struktur pochodzenia blonowego wprowadzono klasyfikacje pecherzykow przede wszystkim na podstawie ich wielkosci i prawdopodobnego mechanizmu powstawania. EVs jako nosniki informacji zawieraja roznorodny material komorkowy, a jednak dzieki intensywnym pracom badawczym coraz wiecej wiadomo o ich funkcji w roznego rodzaju procesach np. nowotworowych. W pracy przedstawiono obecny stan wiedzy na temat pecherzykow blonowych bioracych udzial w szeroko pojetych interakcjach zywiciel-pasozyt, obejmujacych inwazje i kolonizacje zywiciela, ustalanie rownowagi miedzy partnerami czy modulacje odpowiedzi immunologicznej zywiciela w czasie zarazenia. Poruszono kwestie potencjalnego wykorzystania pecherzykow w immunoprofilaktyce oraz diagnostyce chorob inwazyjnych. Najwiecej miejsca poswiecono inwazjom spowodowanym przez pierwotniaki, ze szczegolnym uwzglednieniem parazytoz o najwiekszym znaczeniu medycznym i spolecznym w skali globalnej, co znajduje takze swoje odzwierciedlenie w literaturze swiatowej. Zebrano takze dosc skape na razie doniesienia na temat udzialu EVs w przebiegu inwazji wywolywanych przez gatunki pasozytnicze zaliczane do grupy helmintow. PMID- 27668648 TI - Assessment of the influence of peripheral blood mononuclear cell stimulation with Streptococcus pneumoniae polysaccharides on expression of selected Toll-like receptors, activation markers and Fas antigen in patients with chronic lymphocytic leukemia. AB - INTRODUCTION: Since 2012, both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) have been recommended for pneumococcal infection prevention in patients with chronic lymphocytic leukemia (CLL). Available literature data indicate that leukemic cells may respond to the presence of pathogens through specific Toll-like receptors (TLR). OBJECTIVES: The aim of the study was to assess the effect of in vitro PPV23 stimulation of peripheral blood mononuclear cells (PBMCs) on expression of TLR-2, TLR-4, CD25, CD69, and CD95 on the surface of CD3+ T cells and CD19+ B cells in CLL patients. METHODS: A total of 30 previously untreated patients with CLL, stage 0 according to the Rai classification, were included in the study. PBMCs obtained from each patient were cultured with and without PPV23 antigens. After 24-, 48-, and 72 h cultures, the viable cells underwent labeling with fluorochrome-conjugated monoclonal antibodies, and were analyzed using a flow cytometer. RESULTS: Between 24 h and 72 h (p=0.002) stimulation with PPV23 and between 48 h and 72 h (p=0.034) stimulation with PPV23 the frequencies of CD3+TLR-2+ cells were diminished. Increase of the value of the percentage of CD19+CD69+ cells was observed after 24 h (p=0.003), 48 h (p=0.025) and 72 h (p=0.012) of stimulation with PPV23. Stimulation with PPV23 led to an increase of the percentage of CD19+CD95+ cells after 24 h (p=0.003), 48 h (p=0.015), and 72 h (p=0.006). CONCLUSIONS: We found that both T and B cells respond to antigens of PPV23 by inducing TLR-dependent pathways, lymphocyte activation and CD95 expression. PMID- 27668649 TI - Expression and activity of SNAIL transcription factor during Epithelial to Mesenchymal Transition (EMT) in cancer progression. AB - Inhibition of E-cadherin gene expression by transcription factor SNAIL is known to be a crucial element of Epithelial to Mesenchymal Transition; EMT. Epigenetic regulation of E-cadherin expression is regulated by SNAIL binding to E-box sequences in the CDH1 gene promoter and recruiting enzymes belonging to repressor complexes that are directly engaged in histone modifications and DNA methylation leading to the modification of chromatin structure. SNAIL involvement in cell acquisition of invasive phenotype is based on direct suppression of tight junction and gap junction proteins. The nuclear localization of SNAIL is required for SNAIL activity and protects this factor from proteasomal degradation in the cytoplasm. The main factor engaged in that process is GSK- 3beta kinase. Expression and stability of SNAIL is regulated on the transctriptional and posttranscriptional levels by a number of signaling molecules and biological factors, for example: TGF-beta, TNF-alpha, ILK and NFkappaB. The expression of SNAIL in cancer cells is also regulated by micro-RNA, mainly by miR-34. Increased expression of SNAIL, observed in many human cancers, has been correlated with increased resistance to chemio-, radio - or immunotherapy, gain of cancer stem cells features and migrative and invasive characteristics, which leads to tumor metastases. Understanding of the SNAIL's mechanism of action may lead to new treatment strategies in cancer directed to interfere with signaling pathways that either activate SNAIL or are activated by SNAIL. PMID- 27668650 TI - Adropin - physiological and pathophysiological role. AB - Adropin is a peptide hormone that was discovered in 2008 by Kumar et al. This protein consists of 76 amino acids, and it was originally described as a secreted peptide, with residues 1-33 encoding a secretory signal peptide sequence. The amino acid sequence of this protein in humans, mice and rats is identical. While our knowledge of the exact physiological roles of this poorly understood peptide continues to evolve, recent data suggest a role in energy homeostasis and the control of glucose and fatty acid metabolism. This protein is encoded by the Enho gene, which is expressed primarily in the liver and the central nervous system. The regulation of adropin secretion is controversial. Adropin immunoreactivity has been reported by several laboratories in the circulation of humans, non-human primates and rodents. However, more recently it has been suggested that adropin is a membrane-bound protein that modulates cell-cell communication. Moreover, adropin has been detected in various tissues and body fluids, such as brain, cerebellum, liver, kidney, heart, pancreas, small intestine, endothelial cells, colostrum, cheese whey and milk. The protein level, as shown by previous research, changes in various physiological and pathophysiological conditions. Adropin is involved in carbohydrate-lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. The knowledge of this interesting protein, its exact role and mechanism of action is insufficient. This article provides an overview of the existing literature about the role of adropin, both in physiological and pathophysiological conditions. PMID- 27668651 TI - Bacteriophages to combat foodborne infections caused by food contamination by bacteria of the Campylobacter genus. AB - It is estimated that each year more than 2 million people suffer from diarrheal diseases, resulting from the consumption of contaminated meat. Foodborne infections are most frequently caused by small Gram-negative rods Campylobacter. The hosts of these bacteria are mainly birds wherein they are part of the normal intestinal flora. During the commercial slaughter, there is a likelihood of contamination of carcasses by the bacteria found in the intestinal content. In Europe, up to 90% of poultry flocks can be a reservoir of the pathogen. According to the European Food Safety Authority report from 2015, the number of reported and confirmed cases of human campylobacteriosis exceeds 200 thousands per year, and such trend remains at constant level for several years. The occurrence of growing antibiotic resistance in bacteria forces the limitation of antibiotic use in the animal production. Therefore, the European Union allows only using stringent preventive and hygienic treatment on farms. Achieving Campylobacter free chickens using these methods is possible, but difficult to implement and expensive. Utilization of bacterial viruses - bacteriophages, can be a path to provide the hygienic conditions of poultry production and food processing. Formulations applied in the food protection should contain strictly lytic bacteriophages, be non-pyrogenic and retain long lasting biological activity. Currently, on the market there are available commercial bacteriophage preparations for agricultural use, but neither includes phages against Campylobacter. However, papers on the application of bacteriophages against Campylobacter in chickens and poultry products were published in the last few years. In accordance with the estimates, 2-logarithm reduction of Campylobacter in poultry carcases will contribute to the 30-fold reduction in the incidence of campylobacteriosis in humans. Research on bacteriophages against Campylobacter have cognitive and economic importance. The paper presents current state of research on bacteriophages targeted against Campylobacter. PMID- 27668652 TI - LOSS OF EXTERNAL LIMITING MEMBRANE INTEGRITY PREDICTS PROGRESSION OF HYDROXYCHLOROQUINE RETINAL TOXICITY AFTER DRUG DISCONTINUATION. AB - PURPOSE: To quantify external limiting membrane (ELM) disruption and photoreceptor volume over time, using spectral domain optical coherence tomography in eyes with hydroxychloroquine (HCQ) toxic effects after discontinuation. METHODS: We performed a retrospective chart review of patients who were screened for toxic effects of HCQ between January 1, 2009 and August 31, 2014, and identified 10 patients diagnosed as having HCQ retinal toxic effects. Intact ELM and the Bruch membrane were manually traced using ImageJ software and their lengths from each scan of the spectral domain optical coherence tomography macular volume were summed. The ratio of intact ELM length/Bruch membrane length was calculated. We measured the two-dimensional photoreceptor area between the intact ELM and Bruch membrane in every cross-sectional B-scan. We calculated the total volume of photoreceptors in a volumetric OCT by multiplying photoreceptor area by the distance between B-scans. RESULTS: Of the 10 patients (120 eyes), 1 eye was excluded because of the presence of vitreomacular traction. The mean cumulative dose of HCQ was 1,951 g (range, 584-3,650 g). The mean follow-up duration was 34.1 months (range, 11-64 months). Based on the extent of ELM integrity at diagnosis of HCQ toxicity, we classified eyes into 2 groups: 1) 12 eyes showed severe ELM disruption and 2) 7 eyes had intact ELM. All 19 eyes showed characteristic signs of HCQ toxicity on the visual field examination at the baseline. Seven of 12 eyes with ELM disruption showed progressive ELM changes, including 7 eyes that additionally developed progressive photoreceptor volume decline, whereas 5 eyes remained stable. All 7 eyes with intact ELM remained stable over time. CONCLUSION: Intact ELM status at the time of HCQ discontinuation is a good prognostic sign, and ELM status may allow clinicians to predict patients at risk for progression of retinopathy. Quantitative measurements of ELM disruption and photoreceptors volume may provide an objective tool to monitor outer retinal changes due to HCQ. PMID- 27668653 TI - Epiretinal Membrane Peeling Without Forceps: An Alternative Use of the 27-Gauge Vitrectomy Probe. PMID- 27668654 TI - Treatment of Pulmonary Exacerbations Improves Short But Not Long-Term Growth Trajectory in Children With Cystic Fibrosis. AB - OBJECTIVES: The present study sought to determine the long-term growth consequences after a pulmonary exacerbation in children with cystic fibrosis (CF). METHODS: Retrospective cohort study of pediatric patients with CF with a hospital admission for a pulmonary exacerbation. Logistic regression used to determine risk factors for failure to recover baseline body mass index (BMI) percentile. RESULTS: Of 72 patients, 43% failed to recover their baseline BMI percentile 12 months after discharge and these patients also had a lower forced expiratory volume in 1 second at follow-up. A greater decrease in weight percentile from baseline to admission was the only risk factor identified (odds ratio 0.83, P = 0.0015). CONCLUSIONS: Greater decrease in weight percentile from baseline to admission predicts failure to recover BMI percentile 1 year after a pulmonary exacerbation. Children with CF with poor growth preceding a pulmonary exacerbation continue to be at risk for long-term nutritional failure despite treatment for pulmonary exacerbation. PMID- 27668655 TI - Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy. AB - Immune checkpoint blockade has shown significant promise as an anticancer treatment, yet the determinants of response are not completely understood. Here we show that somatic mutations in SERPINB3 and SERPINB4 are associated with survival after anti-CTLA4 immunotherapy in two independent cohorts of patients with melanoma (n = 174). Interestingly, serpins are homologs of the well-known ovalbumin antigen and are associated with autoimmunity. Our findings have implications for the personalization of immunotherapy. PMID- 27668656 TI - TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons. AB - TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome. PMID- 27668657 TI - Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq. AB - Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and freshly isolated human CD8+ T cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells' transcriptomes, with levels dependent on the cells' transcriptional activity. Notably, clonal aRME was detected, but it was surprisingly scarce (<1% of genes) and mainly affected the most weakly expressed genes. Consequently, the overwhelming majority of aRME occurs transiently within individual cells, and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells. PMID- 27668659 TI - Histone H3K9 methylation is dispensable for Caenorhabditis elegans development but suppresses RNA:DNA hybrid-associated repeat instability. AB - Histone H3 lysine 9 (H3K9) methylation is a conserved modification that generally represses transcription. In Caenorhabditis elegans it is enriched on silent tissue-specific genes and repetitive elements. In met-2 set-25 double mutants, which lack all H3K9 methylation (H3K9me), embryos differentiate normally, although mutant adults are sterile owing to extensive DNA-damage-driven apoptosis in the germ line. Transposons and simple repeats are derepressed in both germline and somatic tissues. This unprogrammed transcription correlates with increased rates of repeat-specific insertions and deletions, copy number variation, R loops and enhanced sensitivity to replication stress. We propose that H3K9me2 or H3K9me3 stabilizes and protects repeat-rich genomes by suppressing transcription induced replication stress. PMID- 27668661 TI - Children's allocation of resources in social dominance situations. AB - Two experiments with preschoolers (36 to 78 months) and 8-year-old children (Experiment 1, N = 173; Experiment 2, N = 132) investigated the development of children's resource distribution in dominance contexts. On the basis of the distributive justice literature, 2 opposite predictions were tested. Children could match resource allocation with the unequal social setting they observe and thus favor a dominant individual over a subordinate 1. Alternatively, children could choose to compensate the subordinate if they consider that the dominance asymmetry should be counteracted. Two experiments using a giving task (Experiment 1) and a taking task (Experiment 2) led to the same results. In both experiments, children took dominance into account when allocating resources. Moreover, their distributive decisions were similarly affected by age: Although 3- and 4-year-old children favored the dominant individual, 5-year-old children showed no preference and 8-year-old children strongly favored the subordinate. Several mechanisms accounting for this developmental pattern are discussed. (PsycINFO Database Record PMID- 27668660 TI - An inducible long noncoding RNA amplifies DNA damage signaling. AB - Long noncoding RNAs (lncRNAs) are prevalent genes with frequently precise regulation but mostly unknown functions. Here we demonstrate that lncRNAs guide the organismal DNA damage response. DNA damage activated transcription of the DINO (Damage Induced Noncoding) lncRNA via p53. DINO was required for p53 dependent gene expression, cell cycle arrest and apoptosis in response to DNA damage, and DINO expression was sufficient to activate damage signaling and cell cycle arrest in the absence of DNA damage. DINO bound to p53 protein and promoted its stabilization, mediating a p53 auto-amplification loop. Dino knockout or promoter inactivation in mice dampened p53 signaling and ameliorated acute radiation syndrome in vivo. Thus, inducible lncRNA can create a feedback loop with its cognate transcription factor to amplify cellular signaling networks. PMID- 27668662 TI - Boron-doped few-walled carbon nanotubes: novel synthesis and properties. AB - Few-walled carbon nanotubes offer a unique marriage of graphitic quality and robustness to ink-processing; however, doping procedures that may alter the band structure of these few-walled nanotubes are still lacking. This report introduces a novel solution-injected chemical vapor deposition growth process to fabricate the first boron-doped few-walled carbon nanotubes (B-FWNTs) reported in literature, which may have extensive applications in battery devices. A comprehensive characterization of the as-grown B-FWNTs confirms successful boron substitution in the graphitic lattice, and reveals varying growth parameters impact the structural properties of B-FWNT yield. An investigation into the optimal growth purification parameters and ink-making procedures was also conducted. This study introduces the first process technique to successfully grow intrinsically p-doped FWNTs, and provides the first investigation into the impact factors of the growth parameters, purification steps, and ink-making processes on the structural properties of the B-FWNTs and the electrical properties of the resulting spray-coated thin-film electrodes. PMID- 27668664 TI - Elegant Shadow Making Tiny Force Visible for Water-Walking Arthropods and Updated Archimedes' Principle. AB - Forces acted on legs of water-walking arthropods with weights in dynes are of great interest for entomologist, physicists, and engineers. While their floating mechanism has been recognized, the in vivo leg forces stationary have not yet been simultaneously achieved. In this study, their elegant bright-edged leg shadows are used to make the tiny forces visible and measurable based on the updated Archimedes' principle. The force was approximately proportional to the shadow area with a resolution from nanonewton to piconewton/pixel. The sum of leg forces agreed well with the body weight measured with an accurate electronic balance, which verified updated Archimedes' principle at the arthropod level. The slight changes of vertical body weight focus position and the body pitch angle have also been revealed for the first time. The visualization of tiny force by shadow is cost-effective and very sensitive and could be used in many other applications. PMID- 27668658 TI - Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps. AB - Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets. PMID- 27668663 TI - Simultaneous Bilateral Versus Staged Bilateral Carpal Tunnel Release: A Cost effectiveness Analysis. AB - : The purpose of this study was to determine if simultaneous bilateral carpal tunnel release (CTR) is a cost-effective strategy compared with bilateral staged CTR for the treatment of bilateral carpal tunnel syndrome. METHODS: A decision analytic model was created to compare the cost effectiveness of three strategies (ie, bilateral simultaneous CTR, bilateral staged CTR, and no treatment). Direct medical costs were estimated from 2013 Medicare reimbursement rates and wholesale drug costs in US dollars. Indirect costs were derived from consecutive patients undergoing unilateral or simultaneous bilateral CTR at our institution and from national average wages for 2013. Health state utility values were derived from a general population of volunteers using the Short Form-6 dimensions (SF-6D) health questionnaire. RESULTS: Both surgical strategies were cost effective compared with the no-treatment strategy. Bilateral simultaneous CTR had lower total costs and higher total effectiveness than bilateral staged CTR, and had an incremental cost-effectiveness ratio of $921 per quality-adjusted life year compared with the no-treatment strategy. The conclusions of the analysis remained unchanged though all sensitivity analyses, displaying robustness against parameter uncertainty. CONCLUSIONS: Surgical management is cost effective for the treatment of bilateral carpal tunnel syndrome. Bilateral simultaneous CTR, however, has lower total costs and higher total effectiveness compared with bilateral staged CTR. LEVEL OF EVIDENCE: Economic and Decision Analysis I. PMID- 27668665 TI - Bottom-Up Fabrication of Hybrid Plasmonic Sensors: Gold-Capped Hydrogel Microspheres Embedded in Periodic Metal Hole Arrays. AB - The high potential of bottom-up fabrication strategies for realizing sophisticated optical sensors combining the high sensitivity of a surface plasmon resonance with the exceptional properties of stimuli-responsive hydrogel is demonstrated. The sensor is composed of a periodic hole array in a gold film whose holes are filled with gold-capped poly(N-isoproyl-acrylamide) (polyNIPAM) microspheres. The production of this sensor relies on a pure chemical approach enabling simple, time-efficient, and cost-efficient preparation of sensor platforms covering areas of cm2. The transmission spectrum of this plasmonic sensor shows a strong interaction between propagating surface plasmon polaritons at the metal film surface and localized surface plasmon resonance of the gold cap on top of the polyNIPAM microspheres. Computer simulations support this experimental observation. These interactions lead to distinct changes in the transmission spectrum, which allow for the simultaneous, sensitive optical detection of refractive index changes in the surrounding medium and the swelling state of the embedded polyNIPAM microsphere under the gold cap. The volume of the polyNIPAM microsphere located underneath the gold cap can be changed by certain stimuli such as temperature, pH, ionic strength, and distinct molecules bound to the hydrogel matrix facilitating the detection of analytes which do not change the refractive index of the surrounding medium significantly. PMID- 27668666 TI - Nanorod-Nanoflake Interconnected LiMnPO4.Li3V2(PO4)3/C Composite for High-Rate and Long-Life Lithium-Ion Batteries. AB - Olivine-type structured LiMnPO4 has been extensively studied as a high-energy density cathode material for lithium-ion batteries. However, preparation of high performance LiMnPO4 is still a large obstacle due to its intrinsically sluggish electrochemical kinetics. Recently, making the composites from both active components has been proven to be a good proposal to improve the electrochemical properties of cathode materials. The composite materials can combine the advantages of each phase and improve the comprehensive properties. Herein, a LiMnPO4.Li3V2(PO4)3/C composite with interconnected nanorods and nanoflakes has been synthesized via a one-pot, solid-state reaction in molten hydrocarbon, where the oleic acid functions as a surfactant. With a highly uniform hybrid architecture, conductive carbon coating, and mutual cross-doping, the LiMnPO4.Li3V2(PO4)3/C composite manifests high capacity, good rate capability, and excellent cyclic stability in lithium-ion batteries. The composite electrodes deliver a high reversible capacity of 101.3 mAh g-1 at the rate up to 16 C. After 4000 long-term cycles, the electrodes can still retain 79.39% and 72.74% of its maximum specific discharge capacities at the rates of 4C and 8C, respectively. The results demonstrate that the nanorod-nanoflake interconnected LiMnPO4.Li3V2(PO4)3/C composite is a promising cathode material for high performance lithium ion batteries. PMID- 27668668 TI - Data Acquisition, Curation, and Use for a Continuously Learning Health System. PMID- 27668667 TI - Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease: A Systematic Review and Meta-analysis. AB - Importance: The association of nonmotor features and Parkinson disease (PD) is increasingly recognized. Evidence suggests that inflammation may play a role in PD pathologic features and symptoms. Objective: To quantitatively summarize the peripheral inflammatory cytokine data available for patients with PD. Data Source: A systematic search of peer-reviewed English-language articles from PubMed, PsycINFO, and the Cochrane Library without year limitation was performed from December 7, 2015, to March 23, 2016. The search terms included inflammation or cytokine or chemokine or tumor necrosis factor or interleukin or interferon or C-reactive protein AND Parkinson disease. Study Selection: Studies were included if they provided data on peripheral blood cytokine concentrations in patients with PD and a healthy control group. Studies were excluded if they contained in vitro analysis of stimulated or unstimulated levels of cytokines, samples that overlapped with other studies, patients not diagnosed with PD at blood sampling, or if the cytokine analyzed was assessed in fewer than 3 studies. Data Extraction and Synthesis: Data were extracted from the 25 included studies encompassing 1547 unique patients with PD and 1107 unique controls by 2 independent investigators. Data were pooled using a random-effects model with the Comprehensive Meta analysis software. Effect sizes were generated as standardized mean differences of cytokine concentrations between patients with PD and healthy controls and converted to the Hedges g statistic. Main Outcomes and Measures: Blood cytokine concentrations in patients with PD compared with controls. Aberrations in peripheral cytokine levels were hypothesized to be related to PD. Results: Among the 2654 study participants, concentrations of interleukin 6 (IL-6) (Hedges g, 0.325; 95% CI, 0.007-0.643; P = .045) in 13 studies, tumor necrosis factor (Hedges g, 0.354; 95% CI, 0.144-0.563; P = .001) in 9 studies, IL-1beta (Hedges g, 0.382; 95% CI, 0.142-0.621; P = .002) in 6 studies, C-reactive protein (Hedges g, 0.323; 95% CI, 0.052-0.593; P = .02) in 6 studies, IL-10 (Hedges g, 0.329; 95% CI, 0.051-0.607; P = .02) in 5 studies, RANTES (regulated on activation, normal T expressed, and presumably secreted) (Hedges g, 0.605; 95% CI, 0.111-1.099; P = .02) in 5 studies, and IL-2 (Hedges g, 0.789; 95% CI, 0.105-1.472; P = .02) in 3 studies were significantly higher in patients with PD compared with healthy controls. No differences were found between patients with PD and healthy controls for concentrations of interferon-gamma (Hedges g, 0.745; 95% CI, -0.192 to 1.682; P = .12) in 5 studies, IL-4 (Hedges g, 0.031; 95% CI, -0.191 to 0.253; P = .79) in 3 studies, and IL-8 (Hedges g, 0.072; 95% CI, -0.136 to 0.279; P = .50) in 3 studies. Conclusions and Relevance: The findings of the meta-analysis demonstrated higher peripheral concentrations of IL-6, tumor necrosis factor, IL 1beta, IL-2, IL-10, C-reactive protein, and RANTES in patients with PD, strengthening the clinical evidence that PD is accompanied by an inflammatory response. PMID- 27668669 TI - A Distal Disulfide Bridge in OXA-1 beta-Lactamase Stabilizes the Catalytic Center and Alters the Dynamics of the Specificity Determining Omega Loop. AB - Widespread antibiotic resistance, particularly when mediated by broad-spectrum beta-lactamases, has major implications for public health. Substitutions in the active site often allow broad-spectrum enzymes to accommodate diverse types of beta-lactams. Substitutions observed outside the active site are thought to compensate for the loss of thermal stability. The OXA-1 clade of class D beta lactamases contains a pair of conserved cysteines located outside the active site that forms a disulfide bond in the periplasm. Here, the effect of the distal disulfide bond on the structure and dynamics of OXA-1 was investigated via 4 MUs molecular dynamics simulations. The results reveal that the disulfide promotes the preorganized orientation of the catalytic residues and affects the conformation of the functionally important Omega loop. Furthermore, principal component analysis reveals differences in the global dynamics between the oxidized and reduced forms, especially in the motions involving the Omega loop. A dynamical network analysis indicates that, in the oxidized form, in addition to its role in ligand binding, the KTG family motif is a central hub of the global dynamics. As activity of OXA-1 has been measured only in the reduced form, we suggest that accurate assessment of its functional profile would require oxidative conditions mimicking periplasm. PMID- 27668670 TI - Health Status Among Adults Born With an Oral Cleft in Norway. AB - Importance: Parents regularly express concern about long-term health outcomes for children who are born with an oral cleft. Objective: To assess whether oral clefts affect the health and ability to work of young adults. Design, Setting, and Participants: A population-based cohort study was conducted on all individuals born in Norway between calendar years 1967 and 1992 (n = 1 490 401). All patients treated for clefts in Norway during the study period were invited to participate (n = 2860). This study used population-based, long-term follow-up data from national registries to focus on the future health outcomes of individuals with cleft and no additional chronic medical conditions or congenital anomalies. A total of 523 individuals were excluded from the study cohort because they declined participation, could not be reached by mail, or had birth defects other than clefts. The final cohort, consisting of 2337 cases with isolated clefts and 1 413 819 unaffected individuals, was followed up until December 31, 2010, using compulsory national registries and clinical data. Data analysis was conducted from February 13, 2014, to April 18, 2016. Exposures: Oral clefts. Main Outcomes and Measures: Death, intellectual disability, schizophrenia, mood affective disorders, anxiety disorders, autism spectrum disorders, attention deficit/hyperactivity disorder, severe learning disability, cerebral palsy, epilepsy, muscle or skeletal disorders, trauma, and episodes of reduced health. Results: Of 2860 individuals born with an oral cleft, 2337 were included in the analysis; of these, 1401 were male (59.9%). Mean (SD) age in 2010 was 30.6 (7.7) years. Compared with unaffected individuals, no increased risks were found regarding morbidity or mortality among persons with isolated cleft lip only. Among individuals with isolated cleft lip and cleft palate, increased risks of intellectual disability (relative risk [RR], 2.2; 95% CI, 1.2-4.1) and cerebral palsy (RR, 2.6; 95% CI, 1.1-6.2) were found. Individuals with isolated cleft palate (ie, without cleft lip) had increased mortality (hazard ratio, 3.4; 95% CI, 2.1-5.7) in addition to an increased risk of intellectual disability (RR, 11.5; 95% CI, 8.5-15.6), anxiety disorders (RR, 2.9; 95% CI, 1.3-6.5), autism spectrum disorders (RR, 6.6; 95% CI, 2.8-15.7), severe learning disabilities (RR, 10.6; 95% CI, 5.5-20.2), cerebral palsy (RR, 4.8; 95% CI, 2.3-10.0), epilepsy (RR, 4.9; 95% CI, 2.2-10.8), and muscle or skeletal disorders (RR, 2.7; 95% CI, 1.4-5.4). Conclusions and Relevance: Young adults who were born with isolated cleft lip only did not differ significantly from unaffected individuals in their risk of health problems. However, individuals with isolated cleft palate had increased health risks and mortality. This information should be provided to genetic counselors, parents of children with clefts, and health care workers involved in the treatment or follow-up of these children. PMID- 27668671 TI - Exercise as Medicine. PMID- 27668672 TI - Antidepressant Prescription in the Geriatric Population: A Teachable Moment. PMID- 27668673 TI - Eosinophilia in a Man With Suspected Acute Coronary Syndrome. PMID- 27668674 TI - More Value From Payment Reform in Health Care and Biomedical Innovation. PMID- 27668675 TI - Construction of Furan Derivatives with a Trifluoromethyl Stereogenic Center: Enantioselective Friedel-Crafts Alkylations via Formal Trienamine Catalysis. AB - An asymmetric Friedel-Crafts alkylation reaction of 2-furfuryl ketones with beta trifluoromethyl enones has been developed via formal trienamine catalysis of a bifunctional primary amine-thiourea substance derived from L-tert-leucine, delivering the furan derivatives incorporating a stereogenic trifluoromethyl (CF3) group in good to high yields with excellent enantioselectivity. PMID- 27668676 TI - Unilateral peripheral corneal thinning with negative workup: April consultation #1. PMID- 27668677 TI - April consultation #2. PMID- 27668678 TI - April consultation #4. PMID- 27668679 TI - April consultation #3. PMID- 27668680 TI - April consultation #5. PMID- 27668681 TI - April consultation #6. PMID- 27668682 TI - April consultation #7. PMID- 27668683 TI - Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of Abeta Self-Aggregation and Therapeutic Applications in Alzheimer's Disease. AB - The complexes cis-[Ru(phen)2(Apy)2]2+, Apy = 4-aminopyridine and 3,4 aminopyridine, are stable in aqueous solution with strong visible absorption. They present emission in the visible region with long lifetime that accumulates in the cytoplasm of Neuro2A cell line without appreciable cytotoxicity. The complexes also serve as mixed-type reversible inhibitors of human AChE and BuChE with high active site contact. cis-[Ru(phen)2(3,4Apy)2]2+ competes efficiently with DMPO by the OH* radical. Luminescence using fluorescence lifetime imaging (FLIM) enables real-time imaging of the conformational changes of the self aggregation of Abeta with incubation of complexes (0-24 h) in phosphate buffer at micromolar concentrations. By this technique, we identified protofibrills in the self-assembly of Abeta1-40 and globular structures in the short fragment Abeta15 21 in aqueous solution. PMID- 27668685 TI - Atomistic Design of CdSe/CdS Core-Shell Quantum Dots with Suppressed Auger Recombination. AB - We design quasi-type-II CdSe/CdS core-shell colloidal quantum dots (CQDs) exhibiting a suppressed Auger recombination rate. We do so using fully atomistic tight-binding wave functions and microscopic Coulomb interactions. The recombination rate as a function of the core and shell size and shape is tested against experiments. Because of a higher density of deep hole states and stronger hole confinement, Auger recombination is found to be up to six times faster for positive trions compared to negative ones in 4 nm core/10 nm shell CQDs. Soft confinement at the interface results in weak suppression of Auger recombination compared to same-bandgap sharp-interface CQDs. We find that the suppression is due to increased volume of the core resulting in delocalization of the wave functions, rather than due to soft-confinement itself. We show that our results are consistent with previous effective mass models with the same system parameters. Increasing the dot volume remains the most efficient way to suppress Auger recombination. We predict that a 4-fold suppression of Auger recombination can be achieved in 10 nm CQDs by increasing the core volume by using rodlike cores embedded in thick shells. PMID- 27668684 TI - Alkylation of Nonacidic C(sp3)-H Bonds by Photoinduced Catalytic Michael-Type Radical Addition. AB - Photoinduced catalytic Michael-type radical addition was achieved via olefin insertion into a nonacidic C(sp3)-H bond, utilizing 2-chloroanthraquinone as a C H bond-cleaving catalyst and 1,1-bis(phenylsulfonyl)ethylene as an olefinic substrate. The present radical protocol allows carbon chain extension stemming from nonacidic C-H bonds, which complements alkylation at acidic C-H bonds under ionic conditions and installs the active methine site that acts as a versatile synthetic handle for further transformations. PMID- 27668686 TI - A New Design Strategy and Diagnostic to Tailor the DNA-Binding Mechanism of Small Organic Molecules and Drugs. AB - The classical model for DNA groove binding states that groove binding molecules should adopt a crescent shape that closely matches the helical groove of DNA. Here, we present a new design strategy that does not obey this classical model. The DNA-binding mechanism of small organic molecules was investigated by synthesizing and examining a series of novel compounds that bind with DNA. This study has led to the emergence of structure-property relationships for DNA binding molecules and/or drugs, which reveals that the structure can be designed to either intercalate or groove bind with calf thymus dsDNA by modifying the electron acceptor properties of the central heterocyclic core. This suggests that the electron accepting abilities of the central core play a key role in the DNA binding mechanism. These small molecules were characterized by steady-state and ultrafast nonlinear spectroscopies. Bioimaging experiments were performed in live cells to evaluate cellular uptake and localization of the novel small molecules. This report paves a new route for the design and development of small organic molecules, such as therapeutics, targeted at DNA as their performance and specificity is dependent on the DNA-binding mechanism. PMID- 27668687 TI - 99mTc-Labeled 2-Arylbenzothiazoles: Abeta Imaging Probes with Favorable Brain Pharmacokinetics for Single-Photon Emission Computed Tomography. AB - A series of 2-arylbenzothiazole derivatives conjugated with bis(aminoethanethiol) (BAT) chelating groups were designed and synthesized. A competitive binding assay based screening was used to select seven rhenium complexes with potent binding affinity toward Abeta1-42 aggregates (Ki < 50 nM) for 99mTc labeling and further evaluation. The 99mTc-labeled probes showed good affinity and specificity to Abeta plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [99mTc]14b exhibited favorable brain pharmacokinetics in normal mice (2.11% ID/g at 2 min and 0.62% ID/g at 60 min). Ex vivo autoradiography revealed extensive labeling of Abeta plaques by [99mTc]14b in the brain of Tg mice. Furthermore, we performed the first single-photon emission computed tomography (SPECT) imaging study in nonhuman primates with 99mTc-labeled Abeta probes. The semiquantitative data showed that [99mTc]14b penetrated the brains of rhesus monkeys. These results indicate that [99mTc]14b could be utilized as a SPECT imaging probe for Abeta plaques. PMID- 27668688 TI - Local Controllable Laser Patterning of Polymers Induced by Graphene Material. AB - Graphene has been successfully applied to the field of polymer laser patterning. As an efficient 1064 nm near-infrared (NIR) pulsed laser absorber, only 0.005 wt % (50 ppm) of graphene prepared by mechanical exfoliation endowed polymer materials with very good NIR pulsed laser patterning. Optical microscopy observed that the generated black patterns came from the local discoloration of the polymer surface subjected to the laser irradiation, and the depth of the discolored layer was determined to be within 221-348 MUm. The X-ray photoelectron spectroscopy confirmed that the polymer surface discoloration was contributed by the local carbonization of polymers caused by graphene due to its high photothermal conversion capacity. Raman depth imaging successfully detected that the generated carbon in the discolored layer was composed of amorphous carbon and complex sp/sp2-carbon compounds containing C=C or conjugated C?C/C=C structures. This study also provides a simple guideline to fabricate laser-patterning polymer materials based on graphene. We believe that graphene has broad application prospects in the field of polymer laser patterning. Importantly, this work opens up a valuable, feasible direction for the practical application of this new carbon material. PMID- 27668689 TI - Conceptual Framework To Extend Life Cycle Assessment Using Near-Field Human Exposure Modeling and High-Throughput Tools for Chemicals. AB - Life Cycle Assessment (LCA) is a decision-making tool that accounts for multiple impacts across the life cycle of a product or service. This paper presents a conceptual framework to integrate human health impact assessment with risk screening approaches to extend LCA to include near-field chemical sources (e.g., those originating from consumer products and building materials) that have traditionally been excluded from LCA. A new generation of rapid human exposure modeling and high-throughput toxicity testing is transforming chemical risk prioritization and provides an opportunity for integration of screening-level risk assessment (RA) with LCA. The combined LCA and RA approach considers environmental impacts of products alongside risks to human health, which is consistent with regulatory frameworks addressing RA within a sustainability mindset. A case study is presented to juxtapose LCA and risk screening approaches for a chemical used in a consumer product. The case study demonstrates how these new risk screening tools can be used to inform toxicity impact estimates in LCA and highlights needs for future research. The framework provides a basis for developing tools and methods to support decision making on the use of chemicals in products. PMID- 27668690 TI - Reconceiving the New World Order: Genes, Reproduction, and the Politics of Regenerative Medicine. PMID- 27668692 TI - Health Literacy-An Important Element in Patient-Centered Outcomes Research. PMID- 27668691 TI - Health Literacy Mediates the Relationship Between Educational Attainment and Health Behavior: A Danish Population-Based Study. AB - Individuals with a lower education level frequently have unhealthier behaviors than individuals with a higher education level, but the pathway is not fully understood. The aim of this study was to investigate whether health literacy mediates the association between educational attainment and health behavior (smoking, physical inactivity, poor diet) and obesity. The study included respondents ages 25 years or older drawn from a large population-based survey conducted in 2013 (N = 29,473). Two scales from the Health Literacy Questionnaire were used: (a) Understanding health information well enough to know what to do and (b) Ability to actively engage with health care providers. Multiple mediation analyses were conducted using the Karlson-Holm-Breen method. The study showed that health literacy in general and the ability to understand health information in particular mediated the relationship between educational attainment and health behavior, especially in relation to being physically inactive (accounting for 20% of the variance), having a poor diet (accounting for 13% of the variance), and being obese (accounting for 16% of the variance). These findings suggest that strategies for improving health behavior and reducing health inequalities may benefit from adopting a stronger focus on health literacy within prevention, patient education, and other public health interventions. PMID- 27668693 TI - Retroperitoneoscopic Partial Nephrectomy for Moderately Complex Ventral Hilar Tumors: Surgical Technique and Trifecta Outcomes from a Single Institution in China. AB - OBJECTIVES: T1 ventral renal hilar tumors (VRHTs) represent a very special type of tumor, for which laparoscopic partial nephrectomy (LPN) by the retroperitoneal approach is challenging. In this study, we report our surgical technique and Trifecta results. METHODS: Renal rotation technique has been established for retroperitoneal laparoscopic partial nephrectomy (RLPN) for VRHTs in our institution. Trifecta was used as a composite outcome measure for assessing quality of PLPN using this technique. A retrospective analysis of RLPN cases in 12 patients with VRHTs was performed. RESULTS: Mean tumor size was 3.4 cm and median R.E.N.A.L. score was 8 (range 7-9). Mean warm ischemia time was 23.1 minutes, suture time 28.1 minutes, estimated blood loss 139.2 mL, operation time 122.8 minutes, and median hospital stay was 4 days. Three patients (25.0%) had Clavien-Dindo grade I-II complications. Seven patients (58.3%) achieved Trifecta. Postoperative pathological examination showed renal cell carcinoma in all cases with negative surgical margin. A median follow-up of 7 months revealed no local recurrence or distant metastases. CONCLUSIONS: Our Trifecta outcomes demonstrate that RLPN with renal rotation technique is feasible, safe, and effective for moderately complex VRHTs. The short-term functional and oncologic outcomes are promising; however, long-term follow-up is needed. PMID- 27668694 TI - Autophagy in osteoarthritis. AB - Osteoarthritis is characterized by continuous degeneration of articular cartilage resulting in disability. The death of chondrocytes and the loss of the extracellular matrix are the central peculiarities in cartilage degeneration during osteoarthritis pathogenesis. Autophagy is an essential cellular homeostasis mechanism whereby cellular organelles and macromolecules are recycled to maintain cellular metabolism. Autophagy is reported to be cytoprotective effects for articular cartilage, and osteoarthritis is associated with decreased autophagy. While autophagy is known to be cytoprotective to chondrocytes, its role may vary with differing stages and models of osteoarthritis. Therefore, more in-depth studies on autophagy are needed to determine its impact on cell survival and death in articular cartilage under various in vitro and in vivo conditions. Application of autophagy on osteoarthritis therapeutics will be possible after a profound understanding is established on the role of autophagy in osteoarthritis pathogenesis. PMID- 27668695 TI - Pharmacokinetic drug interaction study using fimasartan and rosuvastatin in healthy volunteers. AB - OBJECTIVE: This study evaluated the possible pharmacokinetic interactions between rosuvastatin and fimasartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), approved in Korea for the treatment of mild to moderate hypertension. METHODS: In this open-label, multiple-dose, two-period, single-sequence study, the enrolled subjects were randomized into two separate parts (A and B). In part A, subjects received 120 mg of fimasartan alone for 7 days during period I, and 120 mg fimasartan with 20 mg rosuvastatin for 7 days during period II. In Part B, subjects received rosuvastatin alone, followed by concomitant administration of fimasartan, with the same doses used as in Part A. There was a 7-day washout between periods I and II. Serial blood samples were collected for up to 48 hours for fimasartan and for up to 72 hours for rosuvastatin after the last dose of each period to determine the steady-state pharmacokinetics of both drugs. RESULTS: The mean Cmax,ss and AUCtau,ss values of fimasartan were 258.03 +/- 176.75 ng/mL and 746.52 +/- 273.49 ng*h/mL for fimasartan alone, and 289.40 +/- 231.44 ng/mL and 848.43 +/- 267.45 ng*h/mL for fimasartan and rosuvastatin coadministration, respectively (p-values for Cmax,ss and AUCtau,ss, 0. 513 and 0.006, respectively). The mean Cmax,ss and AUCtau,ss values of rosuvastatin were 9.94 +/- 4.48 ng/mL and 85.29 +/- 36.25 ng*h/mL for rosuvastatin alone and 11.94 +/- 8.47 ng/mL and 77.33 +/- 38.71 ng*h/mL for fimasartan and rosuvastatin coadministration, respectively (p-values for Cmax,ss and AUCtau,ss, 0.066 and 0.009, respectively). The geometric mean ratio (GMR) and 90% confidence intervals (CI) for the Cmax,ss and AUCtau,ss of fimasartan (with/without rosuvastatin) were 1.109 (0.813 1.511) and 1.159 (1.061 - 1.265), respectively. The GMR and 90% CI for the Cmax,ss and AUCtau,ss of rosuvastatin (with/without fimasartan) were 1.090 (0.979 - 1.213) and 0.870 (0.804 - 0.940), respectively. CONCLUSIONS: These results suggest that fimasartan and rosuvastatin have no relevant pharmacokinetic drug-drug interactions. All treatments were well tolerated during this study, with no serious adverse effects.?. PMID- 27668696 TI - Corrective effect of norepinephrine on hypotension induced by dexmedetomidine in critically ill patients. AB - PURPOSE: To evaluate the corrective effect of norepinephrine on hypotension induced by dexmedetomidine through monitoring sedation status, hemodynamics as well as oxygen metabolism. METHODS: 100 patients administered standard-dose dexmedetomidine therapy with RASS between -2 and 0 in the intensive care unit (ICU) were included in the study. According to the application of norepinephrine to correct hypotension after dexmedetomidine therapy, the patients were divided into two groups: group A and group B. Group A (dexmedetomidine + norepinephrine group): those who had a systolic arterial pressure < 90 mmHg, a mean arterial pressure < 70 mmHg, or a decline in systolic arterial pressure > 40 mmHg or more than 30% of its base value after dexmedetomidine therapy and then received additional norepinephrine intravenously in order to maintain the arterial pressure at its base value. Group B (dexmedetomidine group): patients received the equivalent dose of dexmedetomidine to maintain the pressure at normal value without extra vasoconstrictor substance. Sedation (CPOT and RASS) and hemodynamic and oxygen metabolism indexes (heart rate, mean arterial pressure, respiratory rate, arterial oxygen saturation, central venous pressure, venous oxygen saturation, arteriovenous carbon dioxide difference, blood lactate level, blood lactate clearance rate, and average hourly urine output) were evaluated in the two groups at baseline, 6th hour, 12th hour, and 24th hour after the administration of intravenous dexmedetomidine. RESULTS: 39 cases were enrolled in group A and 61 cases in group B. Patients of both groups received adequate analgesia and sedation, and there was no significant statistical difference in analgesia and sedation at any point (both p > 0.05). Basal hemodynamic indexes and oxygen metabolism indexes also had no significant statistical difference (both p > 0.05). Central venous pressure (CVP) of group A was significantly higher than that of group B at the 6th hour and 12th hour after administration of intravenous dexmedetomidine (p = 0.005), and the heart rate (HR) of group A was markedly higher than that of group B at the 24th hour after dexmedetomidine therapy (p = 0.017), while the other indexes had no significant difference at any point (both p > 0.05). CONCLUSION: Dexmedetomidine plays an important role in ICU patients due to its pharmacological ability of sedation and analgesia. In our study, dexmedetomidine was successfully applied to ensure goal-directed sedation therapy (GDST). Norepinephrine can correct hypotension and bradycardia induced by intravenous dexmedetomidine. According to the hemodynamic indexes and oxygen metabolism indexes, the application of dexmedetomidine or the combination of dexmedetomidine with norepinephrine are both safe and appropriate to maintain the sedation status and hemodynamic situation in ICU patients.?. PMID- 27668697 TI - Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus?. AB - OBJECTIVE: To study self-administration and pharmacokinetics (PK) of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). METHODS: Patients previously treated with belimumab self-administered belimumab 200 mg SC weekly for 8 weeks using an autoinjector. The primary endpoint was the proportion of patients able to self-administer their first and second dose (weeks 1 and 2) in the clinic. The proportion able to self-administer at weeks 4 and 8 (clinic) and weeks 3, 5, 6, and 7 (home) were secondary endpoints. Belimumab PK, safety, and injection-site pain were assessed. RESULTS: 91/95 patients completed the study (withdrawals: adverse events (AEs): 3; lost to follow-up: 1). 93% were female, and mean (SD) age was 44.8 (12.50) years. The majority (99%, 89/90; no attempt, n = 5) successfully self-administered belimumab SC at weeks 1 and 2 (5 had clinic staff assistance), and 98% (85/87) successfully self-administered at weeks 4 and 8. Home-administration success rates were high (93%, (81/87) at weeks 3, 5, 6, and 7). Week 8 median trough concentration was 113 ug/mL. For patients with a <= 1.5-week interval between IV SC administration, week-1 concentrations were higher vs. week 8 (+ 51% median) but within a range observed with IV dosing; those with a >= 2.5-week interval had median differences close to 0. AEs and serious AEs were low, with no deaths; pain levels were low and decreased with subsequent injections. CONCLUSION: Patients with SLE successfully self administered belimumab SC using a novel autoinjector; the PK profile was stable following a switch from IV with acceptable AE and pain levels. The recommended dosing interval between IV to SC dosing is 1 - 4 weeks.?. PMID- 27668698 TI - Ocular safety of propiverine hydrochloride in elderly patients with primary open- and narrow-angle glaucoma?. AB - BACKGROUND: Propiverine hydrochloride (P4) is an antimuscarinic drug used in overactive bladder syndrome. METHODS: Two studies were performed: one in 24 patients with open-angle glaucoma (OAG) treated with topical beta-blockers, one in 24 patients with narrow-angle glaucoma (NAG) treated with pilocarpine +/- topical beta-blockers. Patients were treated in randomized, placebo-controlled, double-blind parallel-group fashion (15 : 9 attribution to P4 vs. placebo (PL)). TREATMENTS: Single-blind PL dose in the morning of day 1 for baseline; double blind 15 mg P4 or matched placebo t.i.d. from the afternoon of day 1 until the morning of day 7. RESULTS: In the morning of day 7, trough mean serum P4 concentrations were 169.4 ng/mL (CV (coefficient of variation): 0.55) and 140.7 ng/mL (CV: 0.56) in OAG and NAG; at 3:15 hours after dosing: 237.4 ng/mL (CV: 0.47) and 212.4 ng/mL P4 (CV: 0.38), respectively. P4-treatment led to a prompt (OAG) or more gradient (NAG) increase in pupil diameter (PUD), with a maximum difference from PL of 0.97 mm (95% confidence interval (CI): 0.67 - 1.27) and 0.87 mm (95% CI: 0.36 - 1.39) in OAG and NAG, respectively. However, there was no average increase in intraocular pressure (IOP) or increase in noteworthy safety relevant individual IOP values (or changes thereof). There was no effect on visual acuity or accommodation. CONCLUSIONS: 1-week treatment with P4 appeared to be safe 1) in OAG patients treated with topical beta-blockers and 2) in NAG patients treated with topical pilocarpine +/- beta-blockers, irrespective of whether the eyes had previously been treated with glaucoma surgery or laser therapy.?. PMID- 27668699 TI - Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy. AB - INTRODUCTION: Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy that presents in the neonatal period and has been linked previously to mutations in several genes associated with myelination. A recent study has linked 4 homozygous frameshift mutations in the contactin-associated protein 1 (CNTNAP1) gene with this condition. METHODS: We report a neonate with CHN who was found to have absent sensory nerve and compound muscle action potentials and hypomyelination on nerve biopsy. RESULTS: On whole exome sequencing, we identified a novel CNTNAP1 homozygous missense mutation (p.Arg388Pro) in the proband, and both parents were carriers. Molecular modeling suggests that this variant disrupts a beta-strand to cause an unstable structure and likely significant changes in protein function. CONCLUSIONS: This report links a missense CNTNAP1 variant to the disease phenotype previously associated only with frameshift mutations. Muscle Nerve 55: 761-765, 2017. PMID- 27668700 TI - Natural gene expression variation studies in yeast. AB - The rise of sequence information across different yeast species and strains is driving an increasing number of studies in the emerging field of genomics to associate polymorphic variants, mRNA abundance and phenotypic differences between individuals. Here, we gathered evidence from recent studies covering several layers that define the genotype-phenotype gap, such as mRNA abundance, allele specific expression and translation efficiency to demonstrate how genetic variants co-evolve and define an individual's genome. Moreover, we exposed several antecedents where inter- and intra-specific studies led to opposite conclusions, probably owing to genetic divergence. Future studies in this area will benefit from the access to a massive array of well-annotated genomes and new sequencing technologies, which will allow the fine breakdown of the complex layers that delineate the genotype-phenotype map. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27668702 TI - Devil in the detail: a closer look at childhood obesity and the gut microbiota. PMID- 27668703 TI - Metabolic engineering of Escherichia coli W3110 to produce L-malate. AB - A four-carbon dicarboxylic acid L-malate has recently attracted attention due to its potential applications in the fields of medicine and agriculture. In this study, Escherichia coli W3110 was engineered and optimized for L-malate production via one-step L-malate synthesis pathway. First, deletion of the genes encoding lactate dehydrogenase (ldhA), pyruvate oxidase (poxB), pyruvate formate lyase (pflB), phosphotransacetylase (pta), and acetate kinase A (ackA) in pta ackA pathway led to accumulate 20.9 g/L pyruvate. Then, overexpression of NADP+ dependent malic enzyme C490S mutant in this multi-deletion mutant resulted in the direct conversion of pyruvate into L-malate (3.62 g/L). Next, deletion of the genes responsible for succinate biosynthesis further enhanced L-malate production up to 7.78 g/L. Finally, L-malate production was elevated to 21.65 g/L with the L malate yield to 0.36 g/g in a 5 L bioreactor by overexpressing the pos5 gene encoding NADH kinase in the engineered E. coli F0931 strain. This study demonstrates the potential utility of one-step pathway for efficient L-malate production. Biotechnol. Bioeng. 2017;114: 656-664. (c) 2016 Wiley Periodicals, Inc. PMID- 27668704 TI - A nonrandomized, prospective, clinical study on the impact of circulating tumor cells on outcomes of urothelial carcinoma of the bladder patients treated with radical cystectomy with or without adjuvant chemotherapy. AB - To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch(r) system. Platinum-based AC was administered in 50 patients (27.0%). Cox regression models evaluated the association of CTC with disease recurrence, cancer-specific and overall mortality according to AC administration. 185 patients were available for analyses. CTC were present in 41 patients (22.2%). Patients with presence of CTC received AC more frequently, compared to patients without CTC (p = 0.027). At a median follow-up of 31 months, the presence of CTC was associated with disease recurrence, cancer-specific and overall mortality (p values < 0.001) in patients without AC administration. In patients who received AC, there was no difference in either endpoint between patients with or without presence of CTC. In multivariable analysis of patients without AC administration, the presence of CTC was an independent predictor for disease recurrence (HR: 4.9; p < 0.001), cancer-specific (HR: 4.2; p = 0.003) and overall mortality (HR: 4.2; p = 0.001). The CTC status may be implemented in decision-making regarding AC administration in UCB patients following RC. CTC measurement should be implemented in future UCB studies on systemic chemotherapy to validate our findings. PMID- 27668705 TI - Effect of serum YKL-40 on coronary collateral development and SYNTAX score in stable coronary artery disease. AB - OBJECTIVE: Many studies have revealed a role of YKL-40 as a new inflammatory biomarker in angiogenesis, inflammation, atherosclerosis and cardiovascular events. Thus, the aim of this study was to investigate the association of serum YKL-40 level with coronary collateral development and SYNTAX score in patients with stable coronary artery disease. METHODS: A total of 165 patients who had >=90% stenosis in at least one major coronary artery were prospectively enrolled in the study. Collateral degree was graded according to Rentrop-Cohen classification. Patients with grade 2 or 3 collateral degree were included in good collateral group and patients with grade 0 or 1 collateral degree were included in poor collateral group. The patients were also classified according to SYNTAX criteria, those with low (<=22) and those with high (>22) SYNTAX score. RESULTS: Serum YKL-40 and hs-CRP levels were significantly lower in good collateral group. Furthermore, YKL-40 level showed significant positive correlations with SYNTAX score (r=0.486, p<0.001) and hs-CRP level (r=0.340, p<0.001). In multivariate regression analysis, serum YKL-40 (odds ratio: 0.928; 95% confidence interval: 0.917-0.940; p<0.001), duration of ischemic symptom and total occlusion were independent predictors of good collateral development. In ROC curve analysis, a YKL-40 value cut-off point of >=168.5 predicted the high SYNTAX score with a sensitivity of 81.0% and specificity of 72.4%. CONCLUSIONS: Increased serum YKL-40 level was related with poor collateral development and high SYNTAX score. According to these findings YKL-40 can be used as a predictor of good collateral development and high SYNTAX score. PMID- 27668706 TI - Histological evaluation disqualifies IMT and calcification scores as surrogates for grading coronary and aortic atherosclerosis. AB - BACKGROUND/OBJECTIVES: Carotid intimal media thickness (IMT) and coronary calcium scores (CCS) are thought to reflect atherosclerotic burden. The validity of this assumption for IMT is challenged by recent meta-analyses; for CCS by absence of a relationship between negative scores, and freedom of future events. As such, we considered evaluation of the relationship between tissue IMT and CCS, and extend of atherosclerotic disease relevant. METHODS: Analyses were performed on donor aortas obtained during renal graft procurement, and on coronary arteries collected during heart valve procurement for tissue donation. Movat pentachrome and Hematoxylin staining was performed, and the degree of atherosclerosis histologically graded. IMT and presence of calcium deposits were quantified on graded tissue sections. RESULTS: 304 aortas and 185 coronary arteries covering the full atherosclerotic spectrum were evaluated. Aortas and coronaries showed similar relationships between tissue IMT and degree of atherosclerosis, with gradual increase in tissue IMT during earlier phases of atherosclerosis (r=0.68 and r=0.30, P<0.00001 for aorta and coronaries respectively), followed by plateauing of the curve in intermediate and advanced stages. Results for tissue IMT reveal high variability, resulting in wide confidence intervals. Results for CCS are similar for aorta and coronaries, with calcium depositions limited to advanced lesions. CONCLUSIONS: Histological IMT measurements for the aorta and coronaries show large variations around the trend and plateauing of, and possibly reductions in IMT in late stage atherosclerotic disease. These observations for the aorta and coronaries may (partly) explain the limited benefit of including carotid IMT in risk prediction algorithms. PMID- 27668701 TI - Bacterial fatty acid metabolism in modern antibiotic discovery. AB - Bacterial fatty acid synthesis is essential for many pathogens and different from the mammalian counterpart. These features make bacterial fatty acid synthesis a desirable target for antibiotic discovery. The structural divergence of the conserved enzymes and the presence of different isozymes catalyzing the same reactions in the pathway make bacterial fatty acid synthesis a narrow spectrum target rather than the traditional broad spectrum target. Furthermore, bacterial fatty acid synthesis inhibitors are single-targeting, rather than multi-targeting like traditional monotherapeutic, broad-spectrum antibiotics. The single targeting nature of bacterial fatty acid synthesis inhibitors makes overcoming fast-developing, target-based resistance a necessary consideration for antibiotic development. Target-based resistance can be overcome through multi-targeting inhibitors, a cocktail of single-targeting inhibitors, or by making the single targeting inhibitor sufficiently high affinity through a pathogen selective approach such that target-based mutants are still susceptible to therapeutic concentrations of drug. Many of the pathogens requiring new antibiotic treatment options encode for essential bacterial fatty acid synthesis enzymes. This review will evaluate the most promising targets in bacterial fatty acid metabolism for antibiotic therapeutics development and review the potential and challenges in advancing each of these targets to the clinic and circumventing target-based resistance. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. PMID- 27668707 TI - Acutely malapposed bioresorbable vascular scaffold during primary angioplasty for spontaneous coronary artery dissection: Is a no-metal strategy better? PMID- 27668710 TI - Reply by Authors. PMID- 27668708 TI - Usefulness of late gadolinium enhancement MRI combined with stress imaging in predictive significant coronary stenosis in new-diagnosed left ventricular dysfunction. AB - BACKGROUND: To evaluate the accuracy of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) and imaging stress test in predicting significant coronary artery disease (CAD) in left ventricular (LV) dysfunction. METHODS: We enrolled 187 consecutive out-patients (61+/-17years) with new evidence of depressed (<45%) ejection fraction and no history of previous heart diseases and absence of Q-waves. All patients underwent coronary angiography (CA) and to LGE CMR examination to identify ischemic and non-ischemic LGE. All patients underwent stress imaging to determine the presence of myocardial ischemia. RESULTS: Ischemic-LGE was found in 83 patients and non-ischemic-LGE in 104. Significant CAD on CA was found in 86/187 patients. Ischemic-LGE showed a specificity of 94%, a sensitivity of 89% and an accuracy of 92% in identifying significant CAD. Imaging stress test was negative in 98/105 patients without CAD, and positive in 42/82 with significant CAD, showing a specificity of 93%, a sensitivity of 51% and an accuracy of 75% in identifying CAD. Combining CMR and stress test imaging, 94 patients had ischemic-LGE pattern and/or positive stress test for ischemia; of these 81/94 had significant CAD on CA and 13 had no CAD. Among the 93 patients with both tests negative, significant CAD was found in 5/93 patients. The combination of LGE and stress respect to only LGE did not improve the diagnostic accuracy (90 vs 92% respectively). CONCLUSION: LGE-CMR had high accuracy in predicting significant CAD in ischemic LV dysfunction or as a bystander in non ischemic dysfunction. PMID- 27668709 TI - Self-reported symptoms 8weeks after discharge: A comparison of takotsubo syndrome and myocardial infarction. AB - BACKGROUND: Takotsubo syndrome is a form of acute, reversible heart failure that has gained increasing attention. It affects mostly postmenopausal women, and its acute onset and symptoms mimic acute myocardial infarction. The distinct feature of takotsubo syndrome is the ballooning of a ventricle, but the complete pathophysiological mechanisms are not fully understood. Both short-term and long term survival are affected, but little is known about the illness experience and self-reported residual symptoms after discharge from hospital. AIM: To measure and compare self-reported residual symptoms between patients with takotsubo syndrome and those with acute myocardial infarction. METHOD: Questionnaire data measuring self-reported symptoms were collected from 48 patients with takotsubo syndrome and 79 patients with acute myocardial infarction 8weeks after discharge. A multivariate adjusted complete case regression model was used to compare the frequency and severity of symptoms. RESULTS: Self-reported symptoms 8weeks after discharge differed little between patients with takotsubo syndrome and those with acute myocardial infarction. Both groups reported symptoms, including pain, fatigue, breathlessness, and sleep disturbance. At onset there were significant differences between the groups concerning previous diabetes mellitus, cardiac troponin T, ejection fraction and Killip class. There were no significant between group differences in frequency or severity of symptoms after adjusting for these differences. CONCLUSION: Patients with takotsubo syndrome experience residual symptoms after discharge. Symptoms in several cardiovascular diseases predict quality of life, re-admission, and mortality. Symptom management should be integrated into follow-up care for patients with takotsubo syndrome. One way of achieving this is through person-centered care. PMID- 27668711 TI - Editorial Comment. PMID- 27668713 TI - Reply by Authors. PMID- 27668712 TI - Editorial Comment. PMID- 27668714 TI - Editorial Comment. PMID- 27668715 TI - The distribution, contamination and risk assessment of heavy metals in sediment and shellfish from the Red Sea coast, Egypt. AB - Zn, Cu, Ni, V, Al, Pb, Cd, Hg, lipid and water contents were determined in the soft tissues of different shellfish species collected along the Red Sea shoreline. Metal contents showed a descending order of Zn > Cu > Ni > Al > V > Pb > Cd > Hg. The leachable concentrations found in the sediments gathered from the studied locations gave another descending order: Al > Zn > Ni > Pb > V > Cu > Cd. The determined leachable heavy metal contents in the sediment did not exceed the NOAA and CCME (Anonymous 1999) sediment quality guidelines. Accordingly, the sediments along the Egyptian Red Sea area did not pose any adverse impacts on the biological life. According to the hazard quotient (HQ) calculations for heavy metal contents in the soft tissue of shellfish, mercury did not pose any risk on human health; whereas, the other determined heavy metals gave HQ values of 1 < HQ < 10 and showed a possibility of risk on the long term. Cu is above the desirable levels in mussels. The RQ calculations of toddlers and adults reflected that Cu was the only heavy metal that had an adverse effect on toddlers' health. Based on the human organizations (EPA, BOE, MAFF, and NHMRC) that proposed safety concentrations of heavy metals, the studied shellfish were somewhat safe for human consumption. PMID- 27668716 TI - Biomonitoring trace metal contamination by seven sympatric alpine species in Eastern Tibetan Plateau. AB - Biomonitoring permits determinations of trace metal contamination in remote areas like the high mountain ecosystems. In this study, six trace metals (Cd, Cr, Cu, Ni, Pb, and Zn) in seven sympatric alpine species (five tree species: Salix rehderiana, Populus purdomii, Betula albosinensis, Abies fabri, Picea brachytyla, and two dominant mosses: Pleurozium schreberi, Papillaria crocea) at the Hailuogou Glacier foreland, Eastern Tibetan Plateau, were investigated to monitor their contamination. The concentrations of trace metals and Pb isotopic ratios (206Pb/207Pb and 208Pb/206Pb) in leaves/needles, twigs, bark, roots, and mosses were determined, and the biological factors and enrichment factors were calculated. The concentrations of Cd, Cr, Pb, and Zn in mosses were significantly higher than those in tree tissues and normal plants indicating the exogenous sources. The accumulation of trace metals (except Cd and Zn) was relatively higher in the tree roots, whereas their enrichments were significant in the leaves/needles and bark. According to biological factors, enrichment factors, and factor analysis, Cd, Pb, and Zn in trees and mosses were markedly impacted by anthropogenic emissions, whereas Cr, Cu, and Ni in trees were mainly from root adsorption from soils. The Pb isotopic compositions identified the anthropogenic Pb mainly from mining and smelting, coal combustion, and vehicle exhausts. The results indicated that mosses were still priority indicator of trace metal contamination from atmospheric deposition, and the leaves and bark of S. rehderiana, P. purdomii, and B. albosinensis were the better alternatives to monitor the atmospheric contamination of trace metals in the alpine ecosystem. PMID- 27668717 TI - Porous cellulose spheres: Preparation, modification and adsorption properties. AB - Porous cellulose spheres (PCS) were fabricated by precipitating the spheres from a cellulose ionic liquid solution, followed by freezing, solvent exchange, and drying. PCS had low crystallinity and a large surface area that facilitated modification with trisodium trimetaphosphate (STMP) to introduce phosphate ester groups into the porous structure of the heterogeneous system. The STMP-modified PCS (SPCS) were used to remove heavy metal ions from aqueous solution. With increasing STMP dosage, the adsorption capacity of SPCS obviously improved due to chelation between Pb2+ and phosphate ester groups. The kinetic adsorption and isotherm data matched the pseudo-second order model and the Langmuir model well. The maximum adsorption capacity reached 150.6 mg g-1 for SPCS. SPCS were competitive with other absorbents because the phosphate ester groups and porous structure contributed to Pb2+ adsorption. Moreover, SPCS can be regenerated with ethylenediamine tetraacetic acid disodium salt (EDTA) solution for repetitious adsorption of Pb2+. PMID- 27668718 TI - Behavior persistence in defining threshold switch in stepwise response of aquatic organisms exposed to toxic chemicals. AB - As a characteristic in bacterial colony, persistence model described the dynamics of two subpopulations (normal (n) and persister (p)). In order to illustrate the switch of "Threshold" in the stepwise behavior responses of organisms, it is hypothesized that total behavior (Bt) of organisms consists of two types in behavior tendency, intoxication (Bp) and normal/recovery behavior (Bn). Both Bp and Bn could be concurrently affected by environmental stress E, and behavior response modes (M) are decided by the relationship between E and toxicity threshold of test organisms (Ti). The results suggested stress constant lambda was decided by the constant rates gnE,gpE, an and ap. Due to different stress constant lambda, the behavior responses of indicators showed great difference in different M, which included 'safe mode' (Ms), 'acclimation mode' (Mac), 'adjustment mode' (Maj) and 'toxic effect' (Mte). Usually, Bt during Ms could maintain around 0.8, and Mte would happen once it is lower than 0.2. According to the relationship between Bt values and E changes in 7 Majs, behavior persistence relying on adjustment could reflect the behavior homeostasis of organisms under environmental stress and be regarded as a threshold switch for the stepwise behavior responses. The mathematical analysis of behavior persistence allows making a quantitative prediction on environment assessment that would promote the emergence of persistence, as well as evaluating its ecological implications. PMID- 27668719 TI - Retrospective biomonitoring of chemical contamination in the marine coastal environment of Terra Nova Bay (Ross Sea, Antarctica) by environmental specimen banking. AB - Antarctica offers a good opportunity to investigate planetary-scale pollution and climate change, and provides baseline values for contaminants such as Trace Elements (TEs) and Persistent Organic Pollutants (POPs). Literature data on contaminant levels in the Antarctic environment indicate that long-range atmospheric transport is the primary pathway by which pollutants from surrounding continents are carried to this pristine environment. However, local contamination sources represented by the scientific stations are also not negligible. Climate change and global warming are altering the global budget of anthropogenic contaminants and their monitoring in Antarctica ecosystems is very important to protect the global environment. In this work, eighty specimens of Adamussium colbecki (Smith, 1902), a benthic Antarctic scallop, collected from 1996 to 2009 and stored in the Antarctic Environmental Specimen Bank, were analyzed to quantify TEs and POPs, including polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs) and polycyclic aromatic hydrocarbons (PAHs). Metals concentrations were not affected by anthropogenic contributions, highlighting a natural accumulation with the age of the organism. Similarly, no temporal trend was found for PCNs, PCBs and PAHs. However, specimens collected during the summer 1997-98 showed enhanced concentration levels of PCBs and PAHs that could refer to a local anthropogenic source of contamination. PMID- 27668720 TI - Prediction of acute toxicity of phenol derivatives using multiple linear regression approach for Tetrahymena pyriformis contaminant identification in a median-size database. AB - In this article, the modeling of inhibitory grown activity against Tetrahymena pyriformis is described. The 0-2D Dragon descriptors based on structural aspects to gain some knowledge of factors influencing aquatic toxicity are mainly used. Besides, it is done by some enlarged data of phenol derivatives described for the first time and composed of 358 chemicals. It overcomes the previous datasets with about one hundred compounds. Moreover, the results of the model evaluation by the parameters in the training, prediction and validation give adequate results comparable with those of the previous works. The more influential descriptors included in the model are: X3A, MWC02, MWC10 and piPC03 with positive contributions to the dependent variable; and MWC09, piPC02 and TPC with negative contributions. In a next step, a median-size database of nearly 8000 phenolic compounds extracted from ChEMBL was evaluated with the quantitative-structure toxicity relationship (QSTR) model developed providing some clues (SARs) for identification of ecotoxicological compounds. The outcome of this report is very useful to screen chemical databases for finding the compounds responsible of aquatic contamination in the biomarker used in the current work. PMID- 27668721 TI - Ecotoxicological relevance of nano-NiO and acetaminophen to Hordeum vulgare L.: Combining standardized procedures and physiological endpoints. AB - The present work aimed to assess the ecotoxicological relevance of acetaminophen (AC) and nickel oxide nanomaterial (nano-NiO) to barley plants. Combining standard procedures and several biochemical determinations, a global approach regarding the biological effects of these two contaminants was performed. After 14 days of growth, the exposure of barley to increased concentrations (0, 87.8, 131.3, 197.5, 296.5, 444.4, 666.6, and 1000 mg kg-1) of each contaminant resulted in a marked decrease in biomass production and biometric parameters. Photosynthetic pigments and markers of oxidative stress were analyzed to assess if any of the treatments interfered with the physiological performance and with the cellular redox state. Our observations revealed that only nano-NiO induced a negative response in total chlorophylls and carotenoids, confirming the macroscopic phytotoxicity symptoms (chlorosis). However, both contaminants led to a significant increase in lipid peroxidation (LP), superoxide anion (O2.-), and cell death for all the tested concentrations, suggesting that AC and nano-NiO cause oxidative stress in barley, even at the lowest applied dose (87.8 mg kg-1). Comparing the two studied approaches (parameters included in standard protocols and several biochemical determinations), it is concluded that the inclusion of several biochemical endpoints, especially those related to oxidative stress, resulted in a more sensitive analysis and thus, a more sensitive risk evaluation of these two contaminants for barley plants. PMID- 27668722 TI - Effect of single-dose carbapenem exposure on transcriptional expression of blaNDM 1 and mexA in Pseudomonas aeruginosa. AB - The therapeutic option of a carbapenem antibiotic is compromised in Pseudomonas aeruginosa owing both to acquired and intrinsic resistance mechanisms. In recent years, New Delhi metallo-beta-lactamase has been the focus as a predominant carbapenem resistance determinant. However, it is unclear which of the mechanisms might be adopted by a P. aeruginosa strain possessing both blaNDM-1 and an overexpressed MexAB-OprM system during carbapenem therapy. This study investigated the interplay of both mechanisms in clinical isolates of P. aeruginosa when exposed to meropenem. Five strains were used: (i) strain overexpressing MexAB-OprM but with no blaNDM-1; (ii) strain harbouring blaNDM-1 but expressing MexAB-OprM at basal level; (iii) strain possessing blaNDM-1 and overexpressing MexAB-OprM; (iv) P. aeruginosa PAO1; and (v) P. aeruginosa K2733 PAO1 (DeltaMexAB-OprMDeltaMexCD-OprJDeltaMexEF-OprNDeltaMexXY-OprM) into which blaNDM-1 was cloned. Strains were incubated in Luria-Bertani broth with and without 1MUg/mL meropenem. Total RNA was isolated at 45-min intervals and was immediately reverse transcribed to cDNA. This was repeated for 6h. Quantitative real-time PCR was performed for both resistance mechanisms. Meropenem exposure did not significantly elevate transcription of either the blaNDM-1 or mexA gene. However, an interesting finding was that upon single-dose exposure to carbapenem, the efflux pump system played a major role in bacterial survival compared with NDM-1. This study gives an insight into the bacterial response to carbapenem antibiotic when two different resistance mechanisms coexist. This type of study would be helpful in designing future antimicrobials. PMID- 27668724 TI - Sensitive electrochemical assay of alkaline phosphatase activity based on TdT mediated hemin/G-quadruplex DNAzyme nanowires for signal amplification. AB - Taking TdT-mediated hemin/G-quadruplex DNAzyme nanowires as NADH oxidase and HRP mimicking DNAzyme, a novel DNA-based electrochemical method has been developed for sensitive and selective assay of alkaline phosphatase (AP) activity. The double-stranded DNA (dsDNA) probe consisted of thiol-functionalized DNA1 and 3' phosphorylated DNA2, was immobilized on a gold nanoparticles (AuNPs) modified glassy carbon (GC) electrode. In the presence of AP, 3'-phosphoryl end of DNA2 was dephosphorylated. Terminal deoxynucletidyl transferase (TdT) catalyzed the sequential addition of deoxynucleotides (dTTPs) at 3'-OH end of DNA2 to extend DNA2 with a poly-T sequence. Then, G-rich DNA3 strand hybridized with the poly-T sequence of DNA2. Upon addition of hemin, the hemin/G-quadruplex DNAzyme was formed. In the presence of NADH, the hemin/G-quadruplex DNAzyme oxidased NADH to NAD+, accompanied by the formation of H2O2 which was further catalyzed by hemin/G quadruplex DNAzyme (served as a HRP-mimicking DNAzyme) with the thionine (Thi) as electron transfer mediator, leading to the amplified electrochemical signal. Under optimized conditions, the response peak current was linear with the concentration of AP in the range from 0.1UL-1 to 5UL-1 with the detection limit of 0.03UL-1. Also, the developed biosensor possessed good selectivity, reproducibility and stability, and simple sensing structure, showing promising practical applications in AP activity assay. PMID- 27668725 TI - Liquid crystal-based biosensor with backscattering interferometry: A quantitative approach. AB - We developed a new technology that uses backscattering interferometry (BSI) to quantitatively measure nematic liquid crystal (NLC)-based biosensors, those usually relied on texture reading for on/off signals. The LC-based BSI comprised an octadecyltrichlorosilane (OTS)-coated square capillary filled with 4-cyano-4' pentylbiphenyl (5CB, a nematic LC at room temperature). The LC/water interface in the capillary was functionalized by a coating of poly(acrylicacid-b-4 cyanobiphenyl-4'-oxyundecylacrylate) (PAA-b-LCP) and immobilized with the enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP) through covalent linkage to the PAA chains (5CBPAA-GOx:HRP) for glucose detection. Laser irradiation of the LC near the LC/water interface resulted in backscattered fringes with high contrast. The change in the spatial position of the fringes (because of the change in the orientation of the LC caused by the GOx:HRP enzymatic reaction of glucose) altered the output voltage of the photodetector when its active area was aligned with the edge of one of the fringes. The change in the intensity at the photodetector allowed the detection limit of the instrument to be as low as 0.008mM with a linear range of 0.02-9mM in a short response time (~60s). This LC based BSI technique allows for quantitative, sensitive, selective, reproducible, easily obtainable, and interference-free detection in a large linear dynamic range and for practical applications with human serum. PMID- 27668723 TI - Psychological treatment of comorbid asthma and panic disorder in Latino adults: Results from a randomized controlled trial. AB - Confusion between panic and asthma symptoms can result in serious self-management errors. A cognitive behavior psychophysiological therapy (CBPT) intervention was culturally adapted for Latinos consisting of CBT for panic disorder (PD), asthma education, differentiation between panic and asthma symptoms, and heart rate variability biofeedback. An RCT compared CBPT to music and relaxation therapy (MRT), which included listening to relaxing music and paced breathing at resting respiration rates. Fifty-three Latino (primarily Puerto Rican) adults with asthma and PD were randomly assigned to CBPT or MRT for 8 weekly sessions. Both groups showed improvements in PD severity, asthma control, and several other anxiety and asthma outcome measures from baseline to post-treatment and 3-month follow-up. CBPT showed an advantage over MRT for improvement in adherence to inhaled corticosteroids. Improvements in PD severity were mediated by anxiety sensitivity in CBPT and by depression in MRT, although earlier levels of these mediators did not predict subsequent improvements. Attrition was high (40%) in both groups, albeit comparable to CBT studies targeting anxiety in Latinos. Additional strategies are needed to improve retention in this high-risk population. Both CBPT and MRT may be efficacious interventions for comorbid asthma-PD, and CBPT may offer additional benefits for improving medication adherence. PMID- 27668726 TI - Fluorescent trimethyl-substituted naphthyridine as a label-free signal reporter for one-step and highly sensitive fluorescent detection of DNA in serum samples. AB - A facile label-free sensing method is developed for the one-step and highly sensitive fluorescent detection of DNA, which couples the specific C-C mismatch bonding and fluorescent quenching property of a trimethyl-substituted naphthyridine dye (ATMND) with the exonuclease III (Exo III) assisted cascade target recycling amplification strategy. In the absence of target DNA, the DNA hairpin probe with a C-C mismatch in the stem and more than 4 bases overhung at the 3' terminus could entrap and quench the fluorescence of ATMND and resist the digestion of Exo III, thus showing a low fluorescence background. In the presence of the target, however, the hybridization event between the two protruding segments and the target triggers the digestion reaction of Exo III, recycles the initial target, and simultaneously releases both the secondary target analogue and the ATMND caged in the stem. The released initial and secondary targets take part in another cycle of digestion, thus leading to the release of a huge amount of free ATMND for signal transducing. Based on the fluorescence recovery, the as proposed label-free fluorescent sensing strategy shows very good analytical performances towards DNA detection, such as a wide linear range from 10pM to 1MUM, a low limit of detection of 6pM, good selectivity, and a facile one-step operation at room temperature. Practical sample analysis in serum samples indicates the method has good precision and accuracy, which may thus have application potentials for point-of-care screening of DNA in complex clinical and environmental samples. PMID- 27668727 TI - Susceptibility of inhibitors against 3C protease of coxsackievirus A16 and enterovirus A71 causing hand, foot and mouth disease: A molecular dynamics study. AB - Hand foot and mouth disease (HFMD) epidemic has occurred in many countries. Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) are the main causes of HFMD. Up to now, there are no anti-HFMD drugs available. Rupintrivir, a broad spectrum inhibitor, is a drug candidate for HFMD treatment, while other HFMD inhibitors designed from several studies have a relatively low efficiency. Therefore, in this work we aim to study the binding mechanisms of rupintrivir and a peptidic alpha,beta-unsaturated ethyl ester (SG85) against both CV-A16 and EV A71 3C proteases (3Cpro) using all-atoms molecular dynamics simulation. The obtained results indicate that SG85 shows a stronger binding affinity than rupintrivir against CV-A16. Both inhibitors exhibit a comparable affinity against EV-A71 3Cpro. The molecular information of the binding of the two inhibitors to the proteases will be elucidated. Thus, it is implied that these two compounds may be used as leads for further anti-HFMD drug design and development. PMID- 27668728 TI - Hookah Smoking Outcome Expectations Among Young Adults. AB - BACKGROUND: Despite the dangers associated with hookah tobacco smoking, use and popularity in the United States among young adults continue to increase. While quantitative studies have assessed users' attitudes toward hookah, qualitative research can provide a more in-depth description of positive and negative attitudes and beliefs associated with hookah use. OBJECTIVES: To determine outcome expectancies associated with hookah use among young adults. METHODS: We conducted six focus groups in 2013 to identify outcome expectancies associated with hookah use. Participants (N = 40) were young adults aged 18-23 who reported hookah use in the past three months. Using Outcome Expectancy Theory perspective, we posed the question "Hookah smoking is _______?" to elicit words or phrases that users associate with hookah use. RESULTS: Over 75% of the users' hookah use outcome expectancies were positive, including associating hookah smoking with relaxation and a social experience. Content analysis of the words engendered six themes. These themes included Social Appeal, Physical Attractiveness, Pleasant Smoke, Comparison to Cigarettes, Relaxation, and Deterrents. Fewer negative hookah use expectancy words and phrases were identified, but included "tar" and "cough." CONCLUSIONS: The findings suggest that participants lacked basic knowledge about hookah tobacco smoking, had misconceptions about its danger, and had many positive associations with hookah use. Incorporating components addressing positive hookah expectancies may improve the efficacy of established and new hookah use prevention and cessation interventions and policies. PMID- 27668730 TI - Laparoscopic Transcystic Common Bile Duct Exploration: Advantages over Laparoscopic Choledochotomy. AB - PURPOSE: The ideal treatment for choledocholithiasis should be simple, readily available, reliable, minimally invasive and cost-effective for patients. We performed this study to compare the benefits and drawbacks of different laparoscopic approaches (transcystic and choledochotomy) for removal of common bile duct stones. METHODS: A systematic search was implemented for relevant literature using Cochrane, PubMed, Ovid Medline, EMBASE and Wanfang databases. Both the fixed-effects and random-effects models were used to calculate the odds ratio (OR) or the mean difference (MD) with 95% confidence interval (CI) for this study. RESULTS: The meta-analysis included 18 trials involving 2,782 patients. There were no statistically significant differences between laparoscopic choledochotomy for common bile duct exploration (LCCBDE) (n = 1,222) and laparoscopic transcystic common bile duct exploration (LTCBDE) (n = 1,560) regarding stone clearance (OR 0.73, 95% CI 0.50-1.07; P = 0.11), conversion to other procedures (OR 0.62, 95% CI 0.21-1.79; P = 0.38), total morbidity (OR 1.65, 95% CI 0.92-2.96; P = 0.09), operative time (MD 12.34, 95% CI -0.10-24.78; P = 0.05), and blood loss (MD 1.95, 95% CI -9.56-13.46; P = 0.74). However, the LTCBDE group showed significantly better results for biliary morbidity (OR 4.25, 95% CI 2.30-7.85; P<0.001), hospital stay (MD 2.52, 95% CI 1.29-3.75; P<0.001), and hospital expenses (MD 0.30, 95% CI 0.23-0.37; P<0.001) than the LCCBDE group. CONCLUSIONS: LTCBDE is safer than LCCBDE, and is the ideal treatment for common bile duct stones. PMID- 27668729 TI - Genomic Mining of Phylogenetically Informative Nuclear Markers in Bark and Ambrosia Beetles. AB - Deep level insect relationships are generally difficult to resolve, especially within taxa of the most diverse and species rich holometabolous orders. In beetles, the major diversity occurs in the Phytophaga, including charismatic groups such as leaf beetles, longhorn beetles and weevils. Bark and ambrosia beetles are wood boring weevils that contribute 12 percent of the diversity encountered in Curculionidae, one of the largest families of beetles with more than 50000 described species. Phylogenetic resolution in groups of Cretaceous age has proven particularly difficult and requires large quantity of data. In this study, we investigated 100 nuclear genes in order to select a number of markers with low evolutionary rates and high phylogenetic signal. A PCR screening using degenerate primers was applied to 26 different weevil species. We obtained sequences from 57 of the 100 targeted genes. Sequences from each nuclear marker were aligned and examined for detecting multiple copies, pseudogenes and introns. Phylogenetic informativeness (PI) and the capacity for reconstruction of previously established phylogenetic relationships were used as proxies for selecting a subset of the 57 amplified genes. Finally, we selected 16 markers suitable for large-scale phylogenetics of Scolytinae and related weevil taxa. PMID- 27668732 TI - Teaching Health Centers: A Possible Model for Nursing Education. PMID- 27668731 TI - Reducing the Use of Pesticides with Site-Specific Application: The Chemical Control of Rhizoctonia solani as a Case of Study for the Management of Soil-Borne Diseases. AB - Reducing our reliance on pesticides is an essential step towards the sustainability of agricultural production. One approach involves the rational use of pesticides combined with innovative crop management. Most control strategies currently focus on the temporal aspect of epidemics, e.g. determining the optimal date for spraying, regardless of the spatial mechanics and ecology of disease spread. Designing innovative pest management strategies incorporating the spatial aspect of epidemics involves thorough knowledge on how disease control affects the life-history traits of the pathogen. In this study, using Rhizoctonia solani/Raphanus sativus as an example of a soil-borne pathosystem, we investigated the effects of a chemical control currently used by growers, Monceren(r) L, on key epidemiological components (saprotrophic spread and infectivity). We tested the potential "shield effect" of Monceren(r) L on pathogenic spread in a site-specific application context, i.e. the efficiency of this chemical to contain the spread of the fungus from an infected host when application is spatially localized, in our case, a strip placed between the infected host and a recipient bait. Our results showed that Monceren(r) L mainly inhibits the saprotrophic spread of the fungus in soil and may prevent the fungus from reaching its host plant. However, perhaps surprisingly we did not detect any significant effect of the fungicide on the pathogen infectivity. Finally, highly localized application of the fungicide-a narrow strip of soil (12.5 mm wide) sprayed with Monceren(r) L-significantly decreased local transmission of the pathogen, suggesting lowered risk of occurrence of invasive epidemics. Our results highlight that detailed knowledge on epidemiological processes could contribute to the design of innovative management strategies based on precision agriculture tools to improve the efficacy of disease control and reduce pesticide use. PMID- 27668733 TI - Anxiety, Nursing Students, and Simulation: State of the Science. AB - BACKGROUND: The purpose of this state-of-the-science article is to review the existing literature on the effect of anxiety on nursing students' simulation experience and to identify gaps for future research. METHOD: A comprehensive literature review to determine the state of the science focused on anxiety, nursing students, and simulation in peer-reviewed journal articles and dissertations. The review led to a critical appraisal of 10 articles that met the inclusion criteria. RESULTS: Three clear themes emerged from the review: (a) The Unknown, (b) Critique by Peers and Faculty, and (c) The Experience of Making Mistakes. In addition to these themes, knowledge gaps were identified. CONCLUSION: Research is needed to develop interventions to effectively decrease student anxiety during simulation and to develop best practices for student preparation. [J Nurs Educ. 2016;55(10):551-554.]. PMID- 27668734 TI - Development and Testing of the Healthy Work Environment Inventory: A Reliable Tool for Assessing Work Environment Health and Satisfaction. AB - BACKGROUND: Fostering healthy work environments that enhance job satisfaction and reflect high levels of employee engagement and productivity is imperative for all organizations. This is especially true for health care organizations where unhealthy work conditions can lead to poor patient outcomes. METHOD: A convenience sample of 520 nursing faculty and practice-based nurses in the United States participated in a study to test the psychometric properties of the Healthy Work Environment Inventory (HWEI). RESULTS: A factor analysis and other reliability analyses support the use of the HWEI as a valid and reliable instrument to measure perceptions of work environment health. CONCLUSION: The HWEI is a 20-item psychometrically sound instrument to measure perceptions of the health of the work environment. It may be completed either as an individual exercise or by all members of a team to compare perceptions of work environment health, to determine areas of strength and improvement, and to form the basis for interviewing. [J Nurs Educ. 2016;55(10):555-562.]. PMID- 27668736 TI - Shifts in Attitudes, Knowledge, and Social Goals in Nursing Students Following Structured Contact With Community-Dwelling Older Adults. AB - BACKGROUND: Traditional nursing pedagogies have not systematically addressed the ageist perspectives students bring into training that threaten competent care for older adults. The current study evaluated nursing students' shifts in attitudes, knowledge about aging, and social goals during a program of repeated and structured social interactions with community-dwelling older adults. METHOD: Beginning nursing students in pairs met with high-functioning older adults four times over 8 months to provide brief health promotion activities. Students' knowledge and attitudes on aging were assessed at baseline and prior to each visit; social goals were assessed after each visit. RESULTS: Multilevel growth curves revealed increases in students' knowledge about aging and positive views on caring for older adults. Motivation to help older adults (i.e., compassionate goals) did not change, but students' motivation to defend their competence (i.e., self-image goals) declined. CONCLUSION: A relational contact-based program may shift knowledge, attitudes, and social goals in nursing students, complementing traditional classroom nursing education. [J Nurs Educ. 2016;55(10):569-573.]. PMID- 27668735 TI - Recommendations From an Early Adopter of a Doctor of Nursing Practice Program. AB - BACKGROUND: Many changes have occurred in DNP programs since they first began. University of Tennessee Health Science Center began the practice doctoral program in 1999 and today enrolls over 100 new baccalaureate nursing (BSN)-to-Doctor of Nursing Practice (DNP) students each year. More than 500 DNPs have graduated to date. METHOD: A review of the history and challenges of this program are presented as a potential exemplar for other programs to consider. RESULTS: Several changes have taken place, including a shift from Master of Science in Nursing (MSN)-to-DNP programs to almost all BSN-to-DNP programs, a new appreciation for writing skills, and movement away from a separate DNP project. CONCLUSION: Understanding these changes may help other schools of nursing as they begin DNP programs or transition from their MSN-to-DNP programs to BSN-to-DNP programs. [J Nurs Educ. 2016;55(10):563-567.]. PMID- 27668737 TI - A Partnership Approach to Genetic and Genomic Graduate Nursing Curriculum: Report of a New Course's Impact on Student Confidence. AB - BACKGROUND: Genetics and genomics have historically not been included in nursing curricula but are increasingly important in health care delivery. A course was developed through a collaboration between nursing and pathology faculty, combining nursing practice and genomics content expertise. METHOD: Graduate nursing students enrolled in the course self-reported confidence in the 38 American Nurses Association essential genetic and genomic competencies prior to, immediately after, and 9 months after completing the course. RESULTS: Before the course, students reported low confidence across all competencies. Students indicated a significant improvement in confidence in all competencies with an average 2-point improvement on a 5-point Likert scale, both immediately and 9 months after course completion. CONCLUSION: A course rooted in basic science directly linked to nursing application can prepare nurses to develop a sustained confidence in core competencies. Cross-disciplinary collaborations with faculty who have expertise in genomics may be an effective strategy for nursing programs. [J Nurs Educ. 2016;55(10):574-578.]. PMID- 27668738 TI - Developing PhD Nurse Scientists: Do Bachelor of Science in Nursing Honors Programs Help? AB - BACKGROUND: The critical need for more nurses with research doctoral degrees to replace vacancies among retiring nursing faculty and nurse administrators is identified. The Future of Nursing report recommends that the number of nurses with PhD degrees double by 2020. METHOD: Encouraging nursing students to begin doctoral education early in their careers is essential to meeting this goal now and in the future. One method to promote early enrollment into doctoral education is participation in a bachelor of science in nursing (BSN) honors program. We describe the recruitment and application process, mentor selection, scholarly activities, and publication of final manuscripts for one such program. RESULTS: The success of one BSN honors program in enabling graduation with university honors and encouraging enrollment and graduation with doctoral degrees is described. CONCLUSIONS: The development of more BSN Honors programs and enhancement of activities of current programs are recommended. [J Nurs Educ. 2016;55(10):579-582.]. PMID- 27668739 TI - Policy-Focused Service-Learning as a Capstone: Teaching Essentials of Baccalaureate Nursing Education. AB - BACKGROUND: The advancing accountability of nurses and nurse educators requires students to develop knowledge, skills, and judgment on a continuum of focus from individual patients to the broader context of care. METHOD: A dynamic capstone policy course was developed by applying the American Association of Colleges of Nursing's Essentials of Baccalaureate Education for Professional Nursing Practice and capitalizing on related benefits of service-learning pedagogy. It shifts the approach from an intangible didactic lecture on policy and institutional structures to hands-on experiences in actual policy environment and patient health intersections. Acting as nurse consultants, students help clients address a system-based problem. Reflective assignments reinforce student learning as they take cumulative inventory of baccalaureate accomplishments. RESULTS: Competencies in professionalism, teamwork and collaboration, communication, problem solving, and quality assurance are assessed. Students have engaged at sophisticated levels of practice and advocacy. CONCLUSION: Situating capstone service-learning in a nursing policy course appears to sensitize students to perspectives of all ecological levels and desensitizes their discomfort in the policy arena. Implications for research include identifying and implementing measures of success in program outcomes. [J Nurs Educ. 2016;55(10):583-586.]. PMID- 27668740 TI - Development of Formative Capstone Simulations to Prepare Novice Students for Initial Clinical Practicum. AB - BACKGROUND: Nursing students often describe initial clinical experiences as extremely anxiety producing. Anxiety can decrease performance ability and, consequently, increase the risk for patient harm. Strategies to decrease this anxiety related to clinical experiences are limited within the nursing education literature. METHOD: Faculty in a 4-year baccalaureate nursing program developed and implemented formative capstone simulation scenarios with standardized patients, integrating therapeutic communication, essential patient care skills, and clinical reasoning for novice nursing students prior to their entry into their first clinical practicum. This article discusses the rationale, development, and implementation of these formative capstone simulation scenarios. RESULTS: Anecdotal student and faculty comments related to the formative capstone simulation scenarios were positive. CONCLUSIONS: Formative capstone simulation scenarios offer a method to prepare novice students for initial clinical practicum that is well received. Research is needed to formally examine the relationship between formative capstone simulation scenarios and student anxiety related to initial clinical practicum. [J Nurs Educ. 2016;55(10):587-589.]. PMID- 27668741 TI - Use of iPads to Decrease Faculty Workload. AB - BACKGROUND: Multiple faculty were present during a simulation for competency assessments of students, thus creating an increased workload and fatigue. Faculty used technology to reduce the workload and maintain interrater reliability, at little to no cost. METHOD: The use of high-fidelity simulators, tablet computers, and a university video platform were used to record student competency assessments. One faculty member could perform the assessment, but other course faculty could review the results. RESULTS: Seventy-four competency assessments were recorded, and faculty determined that the tablet provided a viable and inexpensive method to record the competency assessments. The ability for faculty to review the recordings helped in maintaining rater and interrater reliability and a method for student remediation. Time spent in the competency assessment, especially during evening hours, was decreased. CONCLUSION: A tablet computer and video platform provided an inexpensive method to reduce faculty contact hours and maintain interrater reliability. It also provided a valuable method to allow students to review their own performance for remediation. [J Nurs Educ. 2016;55(10):590-591.]. PMID- 27668742 TI - Development and Implementation of an Advanced Therapeutic Communication Course: An Interprofessional Collaboration. AB - BACKGROUND: Interprofessional education and practice have been gaining recognition during the past decade. However, little has been written on person centered care (PCC) within interprofessional practice and how it could be taught to interprofessional learners. METHOD: A key element of PCC is therapeutic communication. Consequently, a group of interprofessional faculty innovated a graduate-level elective course on advanced therapeutic communication where interprofessional learners together explore PCC within interprofessional care. The course curriculum is underpinned by mindfulness in education, nonviolent communication, and reflective writing. Various teaching- learning strategies, including creative self-expression, are also used. RESULTS: The created competencies and conceptual framework may be used by other educators in creating a similar interprofessional course. Interprofessional learners gained a deeper and broader understanding of PCC in interprofessional care. CONCLUSION: On the basis of this undertaking, the faculty gained a deeper appreciation for interprofessional collaboration in the development of innovative educational methodologies that advance interprofessional teamwork in education and professional practice. [J Nurs Educ. 2016;55(10):592-597.]. PMID- 27668743 TI - Applying Leadership Theory to Practice Using a Structured Clinical Journal. PMID- 27668744 TI - The Literature Table as a Prompt for Careful Appraisal. PMID- 27668746 TI - Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas-A Retrospective Multicenter Analysis of the German Pancreatitis Study Group. AB - BACKGROUND: Necrotising pancreatitis, and particularly infected necrosis, are still associated with high morbidity and mortality. Since 2011, a step-up approach with lower morbidity rates compared to initial open necrosectomy has been established. However, mortality and complication rates of this complex treatment are hardly studied thereafter. METHODS: The German Pancreatitis Study Group performed a multicenter, retrospective study including 220 patients with necrotising pancreatitis requiring intervention, treated at 10 hospitals in Germany between January 2008 and June 2014. Data were analysed for the primary endpoints "severe complications" and "mortality" as well as secondary endpoints including "length of hospital stay", "follow up", and predisposing or prognostic factors. RESULTS: Of all patients 13.6% were treated primarily with surgery and 86.4% underwent a step-up approach. More men (71.8%) required intervention for necrotising pancreatitis. The most frequent etiology was biliary (41.4%) followed by alcohol (29.1%). Compared to open necrosectomy, the step-up approach was associated with a lower number of severe complications (primary composite endpoint including sepsis, persistent multiorgan dysfunction syndrome (MODS) and erosion bleeding: 44.7% vs. 73.3%), lower mortality (10.5% vs. 33.3%) and lower rates of diabetes mellitus type 3c (4.7% vs. 33.3%). Low hematocrit and low blood urea nitrogen at admission as well as a history of acute pancreatitis were prognostic for less complications in necrotising pancreatitis. A combination of drainage with endoscopic necrosectomy resulted in the lowest rate of severe complications. CONCLUSION: A step-up approach starting with minimal invasive drainage techniques and endoscopic necrosectomy results in a significant reduction of morbidity and mortality in necrotising pancreatitis compared to a primarily surgical intervention. PMID- 27668745 TI - Blood Mercury Levels of Zebra Finches Are Heritable: Implications for the Evolution of Mercury Resistance. AB - Mercury is a ubiquitous metal contaminant that negatively impacts reproduction of wildlife and has many other sub-lethal effects. Songbirds are sensitive bioindicators of mercury toxicity and may suffer population declines as a result of mercury pollution. Current predictions of mercury accumulation and biomagnification often overlook possible genetic variation in mercury uptake and elimination within species and the potential for evolution in affected populations. We conducted a study of dietary mercury exposure in a model songbird species, maintaining a breeding population of zebra finches (Taeniopygia guttata) on standardized diets ranging from 0.0-2.4 MUg/g methylmercury. We applied a quantitative genetics approach to examine patterns of variation and heritability of mercury accumulation within dietary treatments using a method of mixed effects modeling known as the 'animal model'. Significant variation in blood mercury accumulation existed within each treatment for birds exposed at the same dietary level; moreover, this variation was highly repeatable for individuals. We observed substantial genetic variation in blood mercury accumulation for birds exposed at intermediate dietary concentrations. Taken together, this is evidence that genetic variation for factors affecting blood mercury accumulation could be acted on by selection. If similar heritability for mercury accumulation exists in wild populations, selection could result in genetic differentiation for populations in contaminated locations, with possible consequences for mercury biomagnification in food webs. PMID- 27668747 TI - Reducing the Salt Added to Takeaway Food: Within-Subjects Comparison of Salt Delivered by Five and 17 Holed Salt Shakers in Controlled Conditions. AB - OBJECTIVES: To determine if the amount of salt delivered by standard salt shakers commonly used in English independent takeaways varies between those with five and 17 holes; and to determine if any differences are robust to variations in: the amount of salt in the shaker, the length of time spent shaking, and the person serving. DESIGN: Four laboratory experiments comparing the amount of salt delivered by shakers. Independent variables considered were: type of shaker used (five or 17 holes), amount of salt in the shaker before shaking commences (shaker full, half full or nearly empty), time spent shaking (3s, 5s or 10s), and individual serving. SETTING: Controlled, laboratory, conditions. PARTICIPANTS: A quota-based convenience sample of 10 participants (five women) aged 18-59 years. MAIN OUTCOME MEASURES: Amount of salt delivered by salt shakers. RESULTS: Across all trials, the 17 holed shaker delivered a mean (SD) of 7.86g (4.54) per trial, whilst the five holed shaker delivered 2.65g (1.22). The five holed shaker delivered a mean of 33.7% of the salt of the 17 holed shaker. There was a significant difference in salt delivered between the five and 17 holed salt shakers when time spent shaking, amount of salt in the shaker and participant were all kept constant (p<0.001). This difference was robust to variations in the starting weight of shakers, time spent shaking and participant shaking (ps5% frequency in the total sample and Q < 0.05). Thirteen CNVs were identified when Partek algorithm-called CNVs were overlapped with Nexus-identified CNVs; these CNVs showed concordances for frequency, effect size, and direction. Coding genes present within BC-associated CNVs were known to play a role in disease etiology and prognosis. Long noncoding RNAs identified within CNVs showed tissue-specific expression, indicating potential functional relevance of the findings. The identified candidate CNVs warrant independent replication. PMID- 27668789 TI - Evaluation of clinical outcomes and costs based on prescribed dose level of renin angiotensin-aldosterone system inhibitors. PMID- 27668788 TI - The Impact of Parent-Infant Interaction on Epigenetic Plasticity Mediating Synaptic Adaptations in the Infant Brain. AB - The development of the brain depends on an individual's nature (genes) and nurture (environments). This interaction between genetic predispositions and environmental events during brain development drives the maturation of functional brain circuits such as sensory, motor, emotional, and complex cognitive pathways. Adverse environmental conditions such as early life stress can interfere with the functional development of emotional and cognitive brain systems and thereby increase the risk of developing psychiatric disorders later in life. In order to develop more efficient and individualized protective and therapeutic interventions, it is essential to understand how environmental stressors during infancy affect cellular and molecular mechanisms involved in brain maturation. Animal models of early life stress have been able to reveal brain structural and metabolic changes in prefrontolimbic circuits, which are time, brain region, neuron, and sex specific. By focusing on animal models of separation stress during infancy, this review highlights epigenetic and cytoarchitectural modifications which are assumed to mediate lasting changes of brain function and behavior. PMID- 27668790 TI - Flat-Panel CT for Cochlear Implant Electrode Imaging: Comparison to Multi Detector CT. AB - HYPOTHESIS: Flat-panel computed tomography (FPCT) will allow more accurate localization of cochlear implants with decreased metallic artifact and decreased radiation dose when compared with multi-detector CT (MDCT). BACKGROUND: The measurement of scalar location and intra-scalar position of cochlear implantation (CI) electrodes using computed tomography (CT) is complicated by metallic image artifact and insufficient scalar resolution. FPCT has been shown to improve upon the resolution of MDCT while reducing artifact. Previous studies of FPCT imaging employed isolated temporal bones and did not compare FPCT with MDCT. METHODS: A total of 11 CI electrodes (Flex-24, MED-EL Corp, Innsbruck, Austria) were intentionally placed into either the scala tympani (ST) or scala vestibule (SV) in whole cadaver heads and imaged with MDCT and FPCT. The relative radiation dose was measured at the ocular lens for each modality. The implanted cochleae were then isolated and imaged with micro-CT which was used to assess electrode position. Images were reviewed and scored according to electrode array scalar compartment (ST, SV, scala media [SM]), intra-scalar position within each compartment (perimodiolar, mid modiolor, lateral wall) and for the presence of artifact by five readers blinded to the imaging method and approach for electrode insertion. RESULTS: FPCT showed less metallic CI artifact (p = 0.002) and decreased radiation dosage when compared with MDCT. Reviewers were able to identify the scalar compartment and intra-scalar position of all electrodes more accurately with FPCT than with MDCT (p < 0.001). CONCLUSION: FPCT more accurately resolves the scalar compartment and intra-scalar position of CI electrodes with reduced radiation exposure and metallic artifact than MDCT. PMID- 27668791 TI - Serial cVEMP Testing is Sensitive to Disease Progression in Meniere Patients. AB - OBJECTIVE: To assess the cervical vestibular evoked myogenic potentials (cVEMPs) ability to track disease progression in Meniere's disease patients over time and identify the most sensitive outcome measurement. STUDY DESIGN: Retrospective. SETTING: Large specialty hospital, department of otolaryngology. SUBJECTS: Twenty nine Meniere's patients and seven migraine associated vertigo (MAV) patients. INTERVENTION: All patients underwent two cervical vestibular evoked myogenic potential tests at 250, 500, 750, and 1000 Hz with a minimum test interval of 3 months. MAIN OUTCOME MEASURES: Threshold, peak-to-peak (PP) amplitude, interaural asymmetry ratio, and effect size. RESULTS: In affected Meniere's ears all outcome measures were worse during the second test, for threshold this difference was statistically significant at 750 and 1000 Hz compared with the first test. Compared with young healthy ears the threshold was significantly worse at all frequencies. PP amplitude was significantly decreased at the second test at 750 Hz compared with the first test. In MAV no significant difference between tests was found at any frequency in PP amplitude or threshold. In Meniere's ears, threshold showed a higher first-to-second effect size at 500, 750, and 1000 Hz compared with PP amplitude. CONCLUSION: cVEMP is able to track progression in Meniere's disease over time. Thresholds were the most effective outcome measure to both track progression and to distinguish between MAV and Meniere's patients. PMID- 27668794 TI - Intratemporal Intraneural Perineurioma of the Facial Nerve. PMID- 27668793 TI - Single Institutional Experience With Observing 564 Vestibular Schwannomas: Factors Associated With Tumor Growth. AB - OBJECTIVE: To characterize the risk and predictors of growth during observation of vestibular schwannomas (VS). STUDY DESIGN: Retrospective case series. SETTING: Single academic, tertiary care center. PATIENTS: Five hundred sixty-four consecutive VS patients who underwent at least two magnetic resonance imaging (MRI) studies before intervention. INTERVENTION(S): Serial MRI studies. MAIN OUTCOME MEASURE(S): Tumor growth, defined as a >=2 mm increase in the maximum tumor diameter between consecutive MRI studies, or between the first and last study. RESULTS: A total of 1296 patients (1995-2015) with VS were identified. Of those, 564 patients (median age 59.2 years; 53.5% female) were initially observed and underwent multiple MRI studies (median follow-up 22.9 months, interquartile range [IQR] 11.7-42.7). The median maximum tumor diameter at presentation was 1.00 cm (IQR 0.6-1.51 cm). In all, 40.8% of tumors demonstrated growth and 32.1% underwent intervention (21.5% microsurgery, 10.5% radiation) during the surveillance period. Multivariable Cox regression analysis showed that for each tumor, the risk of growth or intervention was significantly increased for larger initial VS diameters (HR = 2.22; 95% CI: 1.90-2.61) and when disequilibrium was a presenting symptom (HR = 1.70; 95% CI: 1.30-2.23). Patient age, sex, aspirin use, and presenting symptoms of asymmetric hearing loss, tinnitus, and vertigo were not associated with tumor growth. CONCLUSION: To date, this is the largest series of observed VS reported in the literature. Risk of VS growth is significantly increased among patients who present with larger tumors and who have concomitant disequilibrium.IRB:: 151481. DEFINE PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: No cohort with this sample size has assessed vestibular schwannoma growth rates in conjunction with this number of variables. LEARNING OBJECTIVE: To characterize vestibular schwannoma growth rates and predictors of growth. PMID- 27668792 TI - Minimally Invasive Surgery for the Treatment of Hyperacusis. AB - OBJECTIVE: To evaluate the efficacy of a minimally invasive surgical procedure in patients with severe hyperacusis. STUDY DESIGN: Prospective, longitudinal design. SETTING: Tertiary referral center. PATIENTS: Adult patients with history of severe hyperacusis. INTERVENTION: Using a transcanal approach, the round and oval window was reinforced with temporalis fascia or tragal perichondrium in six subjects (nine ears) and was subdivided into two groups (unilateral or bilateral reinforcement procedure). MAIN OUTCOME MEASURES: Pre- and postoperative noise tolerance was measured using uncomfortable loudness level (ULL) test scores. In addition, a self-report hyperacusis questionnaire (HQ) was used to assess hypersensitivity to sound before and after the intervention. RESULTS: Analysis of the data reveals improved postoperative mean ULL test scores of 14 dB (confidence interval [CI], 70-98 dB) in the unilateral group. For the bilateral group, improved mean scores were 13 dB (CI, 63-88 dB) in the first ear and 8 dB (CI, 71 86 dB) for the second ear. Further, a negative linear trend was observed in the mean subjective scores for the HQ when both groups measures were analyzed together decreasing from a mean score of 32.0 (standard deviation [SD] = 3.32) preoperative to a mean score of 11.5 (SD = 7.42) after surgery. Postoperatively, the patients reported no change in hearing and improved quality of life after the procedure. CONCLUSION: The results suggest that reinforcement of the round and oval window with temporalis fascia or tragal perichondrium may offer significant benefit for individuals with severe hyperacusis that has not responded to traditional therapy. ULL scores and self-report measures postoperatively demonstrate improved noise tolerance, high patient satisfaction, and enhanced quality of life. PMID- 27668797 TI - Nanomedicine: An iron age for cancer therapy. PMID- 27668795 TI - Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. AB - Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies. PMID- 27668796 TI - Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. AB - The design of cancer-targeting particles with precisely tuned physicochemical properties may enhance the delivery of therapeutics and access to pharmacological targets. However, a molecular-level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (<10 nm in diameter) poly(ethylene glycol)-coated silica nanoparticles, functionalized with melanoma-targeting peptides, can induce a form of programmed cell death known as ferroptosis in starved cancer cells and cancer bearing mice. Tumour xenografts in mice intravenously injected with nanoparticles using a high-dose multiple injection scheme exhibit reduced growth or regression, in a manner that is reversed by the pharmacological inhibitor of ferroptosis, liproxstatin-1. These data demonstrate that ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential. PMID- 27668798 TI - The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. We identified the ubiquitin ligase Huwe1 as a crucial regulator of HSC function via its post-translational control of the oncoprotein N-myc (encoded by Mycn). We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid-fate specification in mice. Through the use of a fluorescent fusion allele (MycnM), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations. N-myc expression was upregulated in response to stress or following loss of Huwe1, which led to increased proliferation and stem cell exhaustion. Mycn depletion reversed most of these phenotypes in vivo, which suggested that the attenuation of N-myc by Huwe1 is essential for reestablishing homeostasis following stress. PMID- 27668799 TI - A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. AB - Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells. PMID- 27668802 TI - Are empathy and concern psychologically distinct? AB - Researchers have long been interested in the relationship between feeling what you believe others feel-often described as empathy-and caring about the welfare of others-often described as compassion or concern. Many propose that empathy is a prerequisite for concern and is therefore the ultimate motivator of prosocial actions. To assess this hypothesis, the authors developed the Empathy Index, which consists of 2 novel scales, and explored their relationship to a measure of concern as well as to measures of cooperative and altruistic behavior. A series of factor analyses reveal that empathy and concern consistently load on different factors. Furthermore, they show that empathy and concern motivate different behaviors: concern for others is a uniquely positive predictor of prosocial action whereas empathy is either not predictive or negatively predictive of prosocial actions. Together these studies suggest that empathy and concern are psychologically distinct and empathy plays a more limited role in our moral lives than many believe. (PsycINFO Database Record PMID- 27668800 TI - CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima. AB - Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19 CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions. PMID- 27668803 TI - Defective iron-oxide nanoparticles synthesised by high temperature plasma processing: a magnetic characterisation versus temperature. AB - Magnetic properties and phase compositions of iron-oxide nanoparticles synthesised by a high temperature arc plasma route have been investigated by Mossbauer spectroscopy and high harmonic magnetic AC susceptibility measurements, and correlated with morphological and structural properties for different synthesis conditions. The Mossbauer spectra precisely determined the presence of different iron-oxide fractions in the investigated nanoparticles, while the high harmonic magnetic susceptibility measurements revealed the occurrence of metastable magnetic phases evolving in temperature and time. This study illustrates magnetic properties and dynamics of the magnetic configurations of iron-oxide nanoparticles grown by high temperature plasma, a process less explored so far but extremely useful for synthesising large numbers of nanoparticles for industrial applications. PMID- 27668801 TI - Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors. AB - Major histocompatibility complex class I (MHC I) positive selection of CD8+ T cells in the thymus requires that T cell antigen receptor (TCR) signaling end in time for cytokines to induce Runx3d, the CD8-lineage transcription factor. We examined the time required for these events and found that the overall duration of positive selection was similar for all CD8+ thymocytes in mice, despite markedly different TCR signaling times. Notably, prolonged TCR signaling times were counter-balanced by accelerated Runx3d induction by cytokines and accelerated differentiation into CD8+ T cells. Consequently, lineage errors did not occur except when MHC I-TCR signaling was so prolonged that the CD4-lineage specifying transcription factor ThPOK was expressed, preventing Runx3d induction. Thus, our results identify a compensatory signaling mechanism that prevents lineage-fate errors by dynamically modulating Runx3d induction rates during MHC I positive selection. PMID- 27668805 TI - Comparison of Graphene Oxide and Reduced Graphene Oxide for DNA Adsorption and Sensing. AB - Fluorescently labeled DNA adsorbed on graphene oxide (GO) is a well-established sensing platform for detecting a diverse range of analytes. GO is a loosely defined material and its oxygen content may vary depending on the condition of preparation. Sometimes, a further reduction step is intentionally performed to decrease the oxygen content, and the resulting material is called reduced GO (rGO). In this study, DNA adsorption and desorption from GO and rGO is systematically compared. Under the same salt concentration, DNA adsorbs slightly faster with a 2.6-fold higher capacity on rGO. At the same time, DNA adsorbed on rGO is more resistant to desorption induced by temperature, pH, urea, and organic solvents. Various lengths and sequences of DNA probes have been tested. When its complementary DNA is added as a model target analyte, the rGO sample has a higher signal-to-background and signal-to-noise ratio, whereas the GO sample has a slightly higher absolute signal increase and faster signaling kinetics. DNAs adsorbed on GO or rGO are still susceptible to nonspecific displacement by other DNA and proteins. Overall, although rGO adsorbs DNA more tightly, it allows efficient DNA sensing with an extremely low background fluorescence signal. PMID- 27668804 TI - Improving Depression Among HIV-Infected Adults: Transporting the Effect of a Depression Treatment Intervention to Routine Care. AB - BACKGROUND: Depression affects 20%-30% of people with HIV. Randomized controlled trials (RCTs) have demonstrated the effectiveness of interventions to improve depression among HIV-infected adults, but typically have highly selected populations which may limit generalizability. Inverse probability of sampling weights (IPSW) is a recently proposed method to transport (or standardize) findings from RCTs to a specific external target population. METHODS: We used IPSW to transport the 6-month effect of the Measurement-Based Care (MBC) intervention on depression from the SLAM DUNC trial to a population of HIV infected, depressed adults in routine care in the United States between 2010 and 2014. RESULTS: In the RCT, MBC was associated with an improvement in depression at 6 months of 3.6 points on the Hamilton Depression Rating scale [95% confidence interval (CI): -5.9 to -1.3]. When IPSW were used to standardize results from the trial to the target population, the intervention effect was attenuated by 1.2 points (mean improvement 2.4 points; 95% CI: -6.1 to 1.3). CONCLUSIONS: If implemented among HIV-infected, depressed adults in routine care, MBC may be less effective than in the RCT but can still be expected to reduce depression. Attenuation of the intervention effect among adults in routine care reflects the fact that the trial enrolled a larger proportion of individuals for whom the intervention was more effective. Given the burden of depression among HIV infected adults, more effective interventions to improve depression are urgently needed. However, examining the transportability of trial findings is essential to understand whether similar effects can be expected if interventions are scaled up. PMID- 27668806 TI - Controlling the Cross-Sensitivity of Carbon Nanotube-Based Gas Sensors to Water Using Zeolites. AB - Carbon nanotube-based gas sensors can be used to detect harmful environmental pollutants such as NO2 at room temperature. Although they show promise as low powered, sensitive, and affordable monitoring devices, cross-sensitivity of functionalized carbon nanotubes to water vapor often obscures the detection of target molecules. This is a barrier to adoption for monitoring of airborne pollutants because of the varying humidity levels found in real world environments. Zeolites, also known as molecular sieves because of their selective adsorption properties, are used in this work to control the cross-sensitivity of single-walled carbon nanotube (SWCNT)-based sensors to water vapor. Zeolites incorporated into the sensing layer are found to reduce interference effects that would otherwise obscure the identification of NO2 gas, permitting repeatable detection over a range of relative humidities. This significant improvement is found to depend on the arrangement of the SWCNT-zeolite layers in the sensing device, as well as the hydrophilicity of the chosen zeolite. PMID- 27668808 TI - Improving Benefit Design to Promote Effective, Efficient, and Affordable Care. PMID- 27668807 TI - Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review. AB - Importance: Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. Objectives: To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. Evidence Review: PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Findings: Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. Conclusions and Relevance: Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies. PMID- 27668809 TI - Kawasaki Disease at 50 Years. AB - Importance: Kawasaki disease (KD) is the most recognized vasculitis of childhood. The condition's characteristic high fever, rash, mucositis, conjunctivitis, lymphadenopathy, and extremity changes are superficially unexceptional, and resolve spontaneously within a mean of 12 days. It is the acuity and the potential for life-changing damage to the coronary arteries that distinguish KD from conditions that mimic it and exemplify the unique aspects and challenges of vascular inflammation in children. Observations: Although KD is an orphan disease, its role as a leading cause of acquired heart disease in children has led to significant efforts to determine its etiology, optimize diagnosis, and customize treatment according to individuals' needs. The result is that KD can now be controlled without sequelae in more than 95% of cases. Furthermore, advances in stratifying patients according to measurable risk factors allow therapy to be personalized in increasingly effective ways. High-risk patients, such as infants younger than 6 months, those with early evidence of coronary artery dilatation, and those with extreme abnormalities in laboratory test results, are often identified at presentation. This early identification allows them to be treated with corticosteroids in addition to intravenous immunoglobulin to improve their outcomes. Children with similar findings on laboratory tests and echocardiography may be treated based on algorithms for managing "incomplete KD" despite falling short of fulfilling classic diagnostic criteria. Children who do not respond to intravenous immunoglobulin are the focus of trials to minimize the duration of inflammation and thereby protect their coronary arteries in ways never before considered. Conclusions and Relevance: Kawasaki disease is a hybrid condition at the junction of infectious diseases, immunology, rheumatology, and cardiology. Rather than being left an orphan disease, KD is bringing disciplines together to identify its genetic, pathophysiological, and hemodynamic features. In turn, this work promises to shed light on many other inflammatory conditions as well. PMID- 27668810 TI - Structure Making and Breaking Effects of Cations in Aqueous Solution: Nitrous Oxide Pump-Probe Measurements. AB - Ultrafast IR pump-probe responses resonant with the nu3 asymmetric stretch of nitrous oxide (N2O) at ~2230 cm-1 are reported for 2 M aqueous salt solutions of MgCl2, CaCl2, NaCl, KCl, and CsCl at room temperature. The solvated cations of these chloride solutions span the range from strongly to weakly hydrating ions, and correspondingly are often categorized as structure makers and structure breakers, respectively. The observed salt dependent trends of the N2O nu3 vibrational energy relaxation (VER) and rotational reorientation anisotropy (R(t)) decays are consistent with the categorization of these cations as structure breakers or makers, and show evidence of effects on the water hydrogen bonding network beyond the first solvation shell of these ions. This N2O mode is resonant with the H2O bend-libration band region. The corresponding FTIR is fitted well by a two Gaussian plus sloping continuum baseline model that allows a framework for characterizing the salt perturbations of the solvent spectral density in the nu3 resonant region. Both coupling strengths and density of states effects appear to contribute the systematic cation dependent T1 effects reported here. R(t) decays follow bulk viscosity values. These results are contrasted with previous IR pump-probe studies predominantly based on the relaxation dynamics of the OH/OD vibrational stretch of HOD hydrogen bonded to anions in salt solutions. PMID- 27668811 TI - Effect of a Structured Exercise Program on the Overall Burden of Major Mobility Disability Among Older Adults. PMID- 27668812 TI - Accreditation Council for Graduate Medical Education (ACGME) Milestones-Time for a Revolt? PMID- 27668813 TI - Simple Measures to Reduce Chemical Exposure. PMID- 27668814 TI - OCEAN: Optimized Cross rEActivity estimatioN. AB - The prediction of molecular targets is highly beneficial during the drug discovery process, be it for off-target elucidation or deconvolution of phenotypic screens. Here, we present OCEAN, a target prediction tool exclusively utilizing publically available ChEMBL data. OCEAN uses a heuristics approach based on a validation set containing almost 1000 drug <- -> target relationships. New ChEMBL data (ChEMBL20 as well as ChEMBL21) released after the validation was used for a prospective OCEAN performance check. The success rates of OCEAN to predict correctly the targets within the TOP10 ranks are 77% for recently marketed drugs and 62% for all new ChEMBL20 compounds and 51% for all new ChEMBL21 compounds. OCEAN is also capable of identifying polypharmacological compounds; the success rate for molecules simultaneously hitting at least two targets is 64% to be correctly predicted within the TOP10 ranks. The source code of OCEAN can be found at http://www.github.com/rdkit/OCEAN. PMID- 27668816 TI - Sustainable Synthesis of Oximes, Hydrazones, and Thiosemicarbazones under Mild Organocatalyzed Reaction Conditions. AB - Pyrrolidine catalyzes very efficiently, presumably via iminium activation, the formation of acyloximes, acylhydrazones, and thiosemicarbazones derived from aromatic and aliphatic aldehydes using equimolar amounts of reagents and green solvents. Experimental simplicity and excellent yields after a simple filtration are the main advantages of the method, being an alternative to those currently available especially for the acyl derivatives, which do not work under uncatalyzed conditions. Its application to the synthesis of acyloximes by direct condensation between aldehydes and acylhydroxylamines is unprecedented. PMID- 27668815 TI - Putting the Health of Communities and Populations First. PMID- 27668818 TI - May consultation #2. PMID- 27668817 TI - Luxated capsule-IOL complex with capsular tension ring lying upside down on retina: May consultation #1. PMID- 27668819 TI - May consultation #3. PMID- 27668820 TI - May consultation #4. PMID- 27668821 TI - May consultation #5. PMID- 27668823 TI - May consultation #7. PMID- 27668822 TI - May consultation #6. PMID- 27668824 TI - No Denying It: Medicinal Chemistry Training Is in Big Trouble. AB - There has been little consensus between the pharmaceutical industry and academic communities concerning the best approach to train medicinal chemists for drug discovery. For decades the pharmaceutical industry has shown preference for synthetic organic graduates over candidates with degrees from medicinal chemistry programs on the assumption that medicinal chemistry expertise will be acquired on the job. However, ongoing changes to pharmaceutical drug discovery organizations and practices threaten to undermine this training model. There is a compelling argument to be made for establishment of a strong industry-academic partnership to train new candidates with sophisticated knowledge of contemporary drug design concepts and techniques to ensure that the future needs of both industry and academic drug discovery research can be served. PMID- 27668825 TI - Synthesis of Isothiazole via the Rhodium-Catalyzed Transannulation of 1,2,3 Thiadiazoles with Nitriles. AB - A synthetic method for obtaining a wide variety of isothiazoles by the Rh catalyzed transannulation of 1,2,3-thiadiazoles with alkyl, aryl, and heteroaryl nitriles, which proceeds via an alpha-thiavinyl Rh-carbenoid intermediate, was developed. The results suggest that during its reaction with nitriles, the alpha thiavinyl carbene acts as an umpolung 1,3-dipole equivalent, in contrast to its behavior during its reaction with alkynes. The developed method was successfully employed to synthesize pentaoligomeric arylene compounds consisting of three benzene and two isothiazole rings. PMID- 27668826 TI - Engineering Topological Surface States of Cr-Doped Bi2Se3 Films by Spin Reorientation and Electric Field. AB - The tailoring of topological surface states in topological insulators is essential for device applications and for exploring new topological phase. Here, we propose a practical way to induce the quantum anomalous Hall phase and unusual metal-insulator transitions in Cr-doped Bi2Se3 films based on the model Hamiltonian and first-principles calculations. Using the combination of in-plane and plane-normal components of the spin along with external electric fields, we demonstrate that the topological state and band structures of topological insulating films exhibit rich features such as the shift of Dirac cones and the opening of nontrivial band gaps. We also show that the in-plane magnetization leads to significant suppression of inter-TSS scattering in Cr-doped Bi2Se3. Our work provides new strategies to obtain the desired electronic structures for the device, complementary to the efforts of an extensive material search. PMID- 27668827 TI - Confined Chemical Etching for Electrochemical Machining with Nanoscale Accuracy. AB - In the past several decades, electrochemical machining (ECM) has enjoyed the reputation of a powerful technique in the manufacturing industry. Conventional ECM methods can be classified as electrolytic machining and electroforming: the former is based on anodic dissolution and the latter is based on cathodic deposition of metallic materials. Strikingly, ECM possesses several advantages over mechanical machining, such as high removal rate, the capability of making complex three-dimensional structures, and the practicability for difficult-to-cut materials. Additionally, ECM avoids tool wear and thermal or mechanical stress on machining surfaces. Thus, ECM is widely used for various industrial applications in the fields of aerospace, automobiles, electronics, etc. Nowadays, miniaturization and integration of functional components are becoming significant in ultralarge scale integration (ULSI) circuits, microelectromechanical systems (MEMS), and miniaturized total analysis systems (MU-TAS). As predicted by Moore's law, the feature size of interconnectors in ULSI circuits are down to several nanometers. In this Account, we present our perseverant research in the last two decades on how to "confine" the ECM processes to occur at micrometer or even nanometer scale, that is, to ensure ECM with nanoscale accuracy. We have been developing the confined etchant layer technique (CELT) to fabricate three dimensional micro- and nanostructures (3D-MNS) on different metals and semiconductor materials since 1992. In general, there are three procedures in CELT: (1) generating the etchant on the surface of the tool electrode by electrochemical or photoelectrochemical reactions; (2) confining the etchant in a depleted layer with a thickness of micro- or nanometer scale; (3) feeding the tool electrode to etch the workpiece. Scavengers, which can react with the etchant, are usually adopted to form a confined etchant layer. Through the subsequent homogeneous reaction between the scavenger and the photo- or electrogenerated etchant in the electrolyte solution, the diffusion distance of the etchant is confined to micro- or nanometer scale, which ensures the nanoscale accuracy of electrochemical machining. To focus on the "confinement" of chemical etching reactions, external physical-field modulations have recently been introduced into CELT by introducing various factors such as light field, force field, hydrodynamics, and so on. Meanwhile, kinetic investigations of the confined chemical etching (CCE) systems are established based on the finite element analysis and simulations. Based on the obtained kinetic parameters, the machining accuracy is tunable and well controlled. CELT is now applicable for 1D milling, 2D polishing, and 3D microfabrication with an accuracy at nanometer scale. CELT not only inherits all the advantages of electrochemical machining but also provides advantages over photolithography and nanoimprint for its applicability to different functional materials without involving any photocuring and thermoplastic resists. Although there are some technical problems, for example, mass transfer and balance, which need to be solved, CELT has shown its prospective competitiveness in electrochemical micromachining, especially in the semiconductor industry. PMID- 27668829 TI - Surfaces with Sustainable Superhydrophobicity upon Mechanical Abrasion. AB - Surfaces with sustainable superhydrophobicity have drawn much attention in recent years for improved durability in practical applications. In this study, hollow mesoporous silica nanoparticles (HMSNs) were prepared and used as reservoirs to load dodecyltrimethoxysilane (DDTMS). Then superhydrophobic surfaces were fabricated by spray coating HMSNs with DDTMS as particle stacking structure and polydimethylsiloxane (PDMS) as hydrophobic interconnection. The mechanical durability of the obtained superhydrophobic surface was evaluated by a cyclic sand abrasion. It was found that once the surface was mechanically damaged, new roughening structures made of the cavity of the HMSNs would expose and maintain suitable hierarchical roughness surrounded by PDMS and DDTMS, favoring sustainable superhydrphobicity of the coating. The surfaces could sustain superhydrophobicity even after 1000 cycles of sand abrasion. This facile strategy may pave the way to the development of robust superhydrophobic surfaces in practical applications. PMID- 27668828 TI - A Carboxylate Shift Regulates Dioxygen Activation by the Diiron Nonheme beta Hydroxylase CmlA upon Binding of a Substrate-Loaded Nonribosomal Peptide Synthetase. AB - The first step in the nonribosomal peptide synthetase (NRPS)-based biosynthesis of chloramphenicol is the beta-hydroxylation of the precursor l-p aminophenylalanine (l-PAPA) catalyzed by the monooxygenase CmlA. The active site of CmlA contains a dinuclear iron cluster that is reduced to the diferrous state (WTR) to initiate O2 activation. However, rapid O2 activation occurs only when WTR is bound to CmlP, the NRPS to which l-PAPA is covalently attached. Here the X ray crystal structure of WTR is reported, which is very similar to that of the as isolated diferric enzyme in which the irons are coordinately saturated. X-ray absorption spectroscopy is used to investigate the WTR cluster ligand structure as well as the structures of WTR in complex with a functional CmlP variant (CmlPAT) with and without l-PAPA attached. It is found that formation of the active WTR:CmlPAT-l-PAPA complex converts at least one iron of the cluster from six- to five-coordinate by changing a bidentately bound amino acid carboxylate to monodentate on Fe1. The only bidentate carboxylate in the structure of WTR is E377. The crystal structure of the CmlA variant E377D shows only monodentate carboxylate coordination. Reduced E377D reacts rapidly with O2 in the presence or absence of CmlPAT-l-PAPA, showing loss of regulation. However, this variant fails to catalyze hydroxylation, suggesting that E377 has the dual role of coupling regulation of O2 reactivity with juxtaposition of the substrate and the reactive oxygen species. The carboxylate shift in response to substrate binding represents a novel regulatory strategy for oxygen activation in diiron oxygenases. PMID- 27668830 TI - Structure-Based Virtual Screening Protocol for in Silico Identification of Potential Thyroid Disrupting Chemicals Targeting Transthyretin. AB - Thyroid disruption by xenobiotics is associated with a broad spectrum of severe adverse outcomes. One possible molecular target of thyroid hormone disrupting chemicals (THDCs) is transthyretin (TTR), a thyroid hormone transporter in vertebrates. To better understand the interactions between TTR and THDCs, we determined the crystallographic structures of human TTR in complex with perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2,2',4,4' tetrahydroxybenzophenone (BP2). The molecular interactions between the ligands and TTR were further characterized using molecular dynamics simulations. A structure-based virtual screening (VS) protocol was developed with the intention of providing an efficient tool for the discovery of novel TTR-binders from the Tox21 inventory. Among the 192 predicted binders, 12 representatives were selected, and their TTR binding affinities were studied with isothermal titration calorimetry, of which seven compounds had binding affinities between 0.26 and 100 MUM. To elucidate structural details in their binding to TTR, crystal structures were determined of TTR in complex with four of the identified compounds including 2,6-dinitro-p-cresol, bisphenol S, clonixin, and triclopyr. The compounds were found to bind in the TTR hormone binding sites as predicted. Our results show that the developed VS protocol is able to successfully identify potential THDCs, and we suggest that it can be used to propose THDCs for future toxicological evaluations. PMID- 27668831 TI - When Health Information Meets Social Media: Exploring Virality on Sina Weibo. AB - This study explored the impacts social media bring about on health communication. The impacts involved four factors: authority, privacy, evidence, and incentive appeals. They were adopted to predict virality of health messages on Sina Weibo in terms of retweeting, endorsing, and replying. A quantitative content analysis was conducted with a two-stage probability sample of 1,261 messages from 34 accounts. The results illustrated two modes Weibo users employed to process health information. The heuristic mode was used for retweeting that was sensitive to public messages, negative appeals, and nonprofessional authority. The systematic mode was used for endorsing and replying that were sensitive to private messages, positive appeals, and both professional and nonprofessional authorities. PMID- 27668832 TI - Tapping Into Motivations for Drinking Among Youth: Normative Beliefs About Alcohol Use Among Underage Drinkers in the United States. AB - Social norms affect human behavior, and underage drinking is no exception. Using the theory of normative social behavior, this study tested the proposition that the association between perceptions about the prevalence of drinking (descriptive norms) and underage drinking is strengthened when perceived pressures to conform (injunctive norms) and beliefs about the benefits of drinking (outcome expectations) are high. This proposition was tested on a nationally representative sample of underage drinkers ages 13-20 (N = 1,031) in relation to their alcohol consumption, expanding on research with college-age youth. On average, males and females reported drinking 23 and 18 drinks per month, respectively. The main effect of descriptive norms (beta = .10, p < .01) on alcohol consumption was modified by interactions with injunctive norms (beta = .11, p < .01), benefit to self (beta = .12, p < .001), and benefit to others (beta = .10, p < .01). Underage drinkers are most vulnerable to excessive drinking if they believe that most others drink, that they themselves are expected to drink, and that drinking confers several benefits. Norms-based interventions to reduce youth alcohol use need to focus on changing not only descriptive norms but also injunctive norms and outcome expectations. PMID- 27668833 TI - The notochord curvature in medaka (Oryzias latipes) embryos as a response to ultraviolet A irradiation. AB - In the present work, the destructive effects of ultraviolet A (UVA; 366nm) irradiation on the developmental stages of Japanese medaka (Oryzias latipes) are revealed in terms of hatching success, mortality rate, and morphological malformations (yolk sac edema, body curvature, fin blistering, and dwarfism). Fertilized eggs in stage 4 were exposed to 15, 30, and 60min/day UVA for 3days in replicates. Fish were staged and aged following the stages established by Iwamatsu [1]. We observed and recorded the hatching time and deformed and dead embryos continuously. The hatching time was prolonged and the deformed and dead embryos numbers were increased by UVA dose increase. At stage 40, samples from each group were fixed to investigate their morphology and histopathology. Some morphological malformations were recorded after UVA exposure in both strains. Histopathological changes were represented as different shapes of curvature in notochord with collapse. The degree of collapsation was depended on the dose and time of UVA exposure. Our findings show that exposure to UVA irradiation caused less vertebral column curvature in medaka fry. Moreover, p53-deficient embryos were more tolerant than those of wild-type (Hd-rR) Japanese medaka. This study indicated the dangerous effects of the UVA on medaka. PMID- 27668835 TI - Laparoscopic Resection and End-to-End Ureteroureterostomy for Midureteral Obstruction in Children. AB - PURPOSE: Midureteral obstruction is an extremely rare condition. This retrospective study assessed the outcomes of laparoscopic ureteroureterostomy (UU) in 13 children with midureteral obstructions. METHODS: Records of patients with midureteral obstruction who underwent laparoscopic end-to-end UU between July 2011 and August 2015 were reviewed. The medical records comprised patient demographic data, intraoperative details, postoperative outcomes, and related complications. Renal ultrasound, magnetic resonance urography, and radioisotope renography were used for pre- and postoperative assessment. Success was defined as removal of symptomatic obstruction or improvement of hydronephrosis. RESULTS: Thirteen patients from 3.0 months to 12 years old were identified: 6 patients presented with asymptomatic hydronephrosis (according to the renal ultrasonography), 3 with intermittent abdominal pain, and 2 with gross hematuria. The remaining 2 patients presented with urinary extravasation after inguinal hernia repair and the Soave procedure, respectively. All patients underwent laparoscopic end-to-end UU. Procedures were performed using either the laparoscopic transperitoneal approach or laparoscopic retroperitoneal approach. All surgeries were performed successfully except for one case that required open surgery because of difficult anastomosis. There were no intraoperative or immediate postoperative complications. The etiology of the midureteral obstruction included congenital midureteral stricture, ureteral polyp, retrocaval ureter, and iatrogenic injury. The mean surgical time was 148.4 min, and postoperative hospital stay was 4.0-9.0 d. Postoperative outcomes were successful in all 13 patients (100%); median follow-up was 19.1 months. CONCLUSION: Laparoscopic UU was found to be feasible and safe for the management of midureteral obstruction in children. PMID- 27668834 TI - The Association of Graph Literacy With Use of and Skills Using an Online Personal Health Record in Outpatient Veterans. AB - Personal health records (PHRs) are intended to increase patients' access to and ownership over their health care information for self-management purposes. The purpose of this study was to determine the association of graph literacy with adoption of an online PHR and, among adopters with self-reported skills, the frequency of use and intent to return to use the PHR . We conducted a cross sectional survey of veterans receiving outpatient care. We measured health literacy, numeracy, graph literacy, and Internet and PHR adoption and use. We compared subgroups of veterans using analyses of covariance. We used hierarchical logistic regression models to estimate the effects of the literacy variables on PHR use. A total of 600 veterans (age = 22-94) participated in the survey. After we adjusted for known covariates, we found that adopters of a PHR were more likely to demonstrate higher health and graph literacy than nonadopters. Among PHR adopters, self-reported frequent and skillful users were more likely to have higher graph literacy than lower frequency and less skillful users. Adopters with higher intentions to return to use the PHR were more likely to show lower graph literacy than those less likely to return to use the PHR. Inadequate graph literacy was associated with lower adoption of a PHR and, among users, with lower self-reported frequent use and skills . As PHR use becomes more widespread, stakeholders will need to consider patients' levels of graph literacy when implementing PHRs. PMID- 27668836 TI - Reorganization of neural systems mediating peripheral visual selective attention in the deaf: An optical imaging study. AB - Theories of brain plasticity propose that, in the absence of input from the preferred sensory modality, some specialized brain areas may be recruited when processing information from other modalities, which may result in improved performance. The Useful Field of View task has previously been used to demonstrate that early deafness positively impacts peripheral visual attention. The current study sought to determine the neural changes associated with those deafness-related enhancements in visual performance. Based on previous findings, we hypothesized that recruitment of posterior portions of Brodmann area 22, a brain region most commonly associated with auditory processing, would be correlated with peripheral selective attention as measured using the Useful Field of View task. We report data from severe to profoundly deaf adults and normal hearing controls who performed the Useful Field of View task while cortical activity was recorded using the event-related optical signal. Behavioral performance, obtained in a separate session, showed that deaf subjects had lower thresholds (i.e., better performance) on the Useful Field of View task. The event related optical data indicated greater activity for the deaf adults than for the normal-hearing controls during the task in the posterior portion of Brodmann area 22 in the right hemisphere. Furthermore, the behavioral thresholds correlated significantly with this neural activity. This work provides further support for the hypothesis that cross-modal plasticity in deaf individuals appears in higher order auditory cortices, whereas no similar evidence was obtained for primary auditory areas. It is also the only neuroimaging study to date that has linked deaf-related changes in the right temporal lobe to visual task performance outside of the imaging environment. The event-related optical signal is a valuable technique for studying cross-modal plasticity in deaf humans. The non invasive and relatively quiet characteristics of this technique have great potential utility in research with clinical populations such as deaf children and adults who have received cochlear or auditory brainstem implants. PMID- 27668837 TI - [Formula: see text]Education, training and practice of clinical neuropsychologists in the United States of America. AB - OBJECTIVE: This invited paper is intended to give an overview regarding the education and training pathways for the practice of neuropsychology in the United States. It is also meant to describe the types of activities engaged in by neuropsychologists, a description of their work settings and the amounts/ways in which they are compensated for their work. METHOD: The authors reviewed the literature and relied on their professional and organizational experiences to collect the necessary data. RESULTS: The United States has well-defined pathways for one to follow to gain the experiences and knowledge necessary to practice clinical neuropsychology in a competent way. Compensation varies widely among workplace settings but overall neuropsychologists appear to be well-paid. Challenges now and in the foreseeable future include a need to develop tests that have better ecological validity and that better reflect the demographics of a changing population, and an increasing need for neuropsychologists to identify key roles as members of integrated care teams. CONCLUSIONS: The United States has played an important role in the development of the practice and science of neuropsychology. Its continued success will, at least in part, depend on innovations in test development and application, and further demonstration of its relevance to health care and academic settings. PMID- 27668838 TI - Muscle MRI of classic infantile pompe patients: Fatty substitution and edema-like changes. AB - INTRODUCTION: The aim of this study was to evaluate the muscle MRI pattern of 9 patients (median age: 6.5 +/- 2.74 years) affected by classic infantile-onset Pompe disease who were treated with enzyme replacement therapy. METHODS: We performed and qualitatively scored T1-weighted (T1-w) sequences of the facial, shoulder girdle, paravertebral, and lower limb muscles and short-tau inversion recovery (STIR) sequences of the lower limbs using the Mercuri and Morrow scales, respectively. RESULTS: On T1-w images, mild (grade 1) or moderate (grade 2) involvement was found in the tongue in 6 of 6 patients and in the adductor magnus muscle in 6 of 9. STIR hyperintensity was detected in all areas examined and was categorized as limited to mild in 5 of 8 patients. CONCLUSIONS: On T1-w sequences, mild/moderate adipose substitution in the adductor magnus and tongue muscles was documented. STIR edema-like alterations of thigh and calf muscles are novel findings. Correlations with biopsy findings and clinical parameters are needed to fully understand these findings. Muscle Nerve 55: 841-848, 2017. PMID- 27668840 TI - Ankle-brachial index and brachial-ankle pulse wave velocity are associated with albuminuria in community-based Han Chinese. AB - BACKGROUND/OBJECTIVES: Our study aimed to explore whether the ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were associated with albuminuria in community-based Han Chinese. METHODS: Total 2127 subjects (860 men and 1267 women) aged 60 years and over were recruited in Beijing. Albuminuria was assessed by the urinary albumin-to-creatinine ratio (UACR) of >=30 mg/g. BaPWV was divided by quartile. The logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (CIs) of ABI and baPWV with albuminuria. RESULTS: ABI was associated with albuminuria in the interaction model (OR 0.89, 95% CI 0.81-0.99 by every 0.1 unit increase of ABI), especially in hypertension (OR 0.82, 95% CI 0.73-0.92) and diabetes (OR 0.83, 95% CI 0.68-0.98) groups. BaPWV groups were also significantly associated with albuminuria, ORs of having albuminuria for baPWV quartile II, III, and IV were 1.02(0.65-1.52), 1.05(0.72 1.61), and 1.18(1.04-1.47) in the interaction model. For hypertension and diabetes patients, only the baPWV quartile IV group had higher OR. CONCLUSIONS: ABI and baPWV were associated with albuminuria after adjusting for other risk factors in Chinese community-based elderly Han population. The association of ABI with albuminuria was stronger in hypertension and diabetes patients. PMID- 27668841 TI - Rapid Response Teams: Is it Time to Reframe the Questions of Rapid Response Team Measurement? AB - PURPOSE: The purpose of this article is to present an overview of rapid response team (RRT) history in the United States, provide a review of prior RRT effectiveness research, and propose the reframing of four new questions of RRT measurement that are designed to better understand RRTs in the context of contemporary nursing practice as well as patient outcomes. ORGANIZING CONSTRUCT: RRTs were adopted in the United States because of their intuitive appeal, and despite a lack of evidence for their effectiveness. Subsequent studies used mortality and cardiac arrest rates to measure whether or not RRTs "work." Few studies have thoroughly examined the effect of RRTs on nurses and on nursing practice. METHODS: An extensive literature review provided the background. Suppositions and four critical, unanswered questions arising from the literature are suggested. FINDINGS: The results of RRT effectiveness, which have focused on patient-oriented outcomes, have been ambiguous, contradictory, and difficult to interpret. Additionally, they have not taken into account the multiple ways in which these teams have impacted nurses and nursing practice as well as patient outcomes. CONCLUSIONS: What happens in terms of RRT process and utilization is likely to have a major impact on nurses and nursing care on general medical and surgical wards. What that impact will be depends on what we can learn from measuring with an expanded yardstick, in order to answer the question, "Do RRTs work?" CLINICAL RELEVANCE: Evidence for the benefits of RRTs depends on proper framing of questions relating to their effectiveness, including the multiple ways RRTs contribute to nursing efficacy. PMID- 27668839 TI - Proteomic and genomic characterization of a yeast model for Ogden syndrome. AB - Naa10 is an Nalpha -terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the alpha-amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40-50% of the human proteome is acetylated by Naa10, rendering this an enzyme one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harbouring a c.109 T > C (p.Ser37Pro) variant in NAA10. In the present study we performed in-depth characterization of a yeast model of Ogden syndrome. Stress tests and proteomic analyses suggest that the S37P mutation disrupts Naa10 function and reduces cellular fitness during heat shock, possibly owing to dysregulation of chaperone expression and accumulation. Microarray and RNA-seq revealed a pseudo-diploid gene expression profile in DeltaNaa10 cells, probably responsible for a mating defect. In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes potentially contributing to the severe phenotype seen in Ogden syndrome. Data are available via GEO under identifier GSE86482 or with ProteomeXchange under identifier PXD004923. (c) 2016 The Authors. Yeast published by John Wiley & Sons, Ltd. PMID- 27668842 TI - Phylogeography and pigment type diversity of Synechococcus cyanobacteria in surface waters of the northwestern pacific ocean. AB - The widespread unicellular cyanobacteria Synechococcus are major contributors to global marine primary production. Here, we report their abundance, phylogenetic diversity (as assessed using the RNA polymerase gamma subunit gene rpoC1) and pigment diversity (as indirectly assessed using the laterally transferred cpeBA genes, encoding phycoerythrin-I) in surface waters of the northwestern Pacific Ocean, sampled over nine distinct cruises (2008-2015). Abundance of Synechococcus was low in the subarctic ocean and South China Sea, intermediate in the western subtropical Pacific Ocean, and the highest in the Japan and East China seas. Clades I and II were by far the most abundant Synechococcus lineages, the former dominating in temperate cold waters and the latter in (sub)tropical waters. Clades III and VI were also fairly abundant in warm waters, but with a narrower distribution than clade II. One type of chromatic acclimater (3dA) largely dominated the Synechococcus communities in the subarctic ocean, while another (3dB) and/or cells with a fixed high phycourobilin to phycoerythrobilin ratio (pigment type 3c) predominated at mid and low latitudes. Altogether, our results suggest that the variety of pigment content found in most Synechococcus clades considerably extends the niches that they can colonize and therefore the whole genus habitat. PMID- 27668843 TI - Development of in situ product removal strategies in biocatalysis applying scaled down unit operations. AB - An experimental platform based on scaled-down unit operations combined in a plug and-play manner enables easy and highly flexible testing of advanced biocatalytic process options such as in situ product removal (ISPR) process strategies. In such a platform, it is possible to compartmentalize different process steps while operating it as a combined system, giving the possibility to test and characterize the performance of novel process concepts and biocatalysts with minimal influence of inhibitory products. Here the capabilities of performing process development by applying scaled-down unit operations are highlighted through a case study investigating the asymmetric synthesis of 1-methyl-3 phenylpropylamine (MPPA) using omega-transaminase, an enzyme in the sub-family of amino transferases (ATAs). An on-line HPLC system was applied to avoid manual sample handling and to semi-automatically characterize omega-transaminases in a scaled-down packed-bed reactor (PBR) module, showing MPPA as a strong inhibitor. To overcome the inhibition, a two-step liquid-liquid extraction (LLE) ISPR concept was tested using scaled-down unit operations combined in a plug-and-play manner. Through the tested ISPR concept, it was possible to continuously feed the main substrate benzylacetone (BA) and extract the main product MPPA throughout the reaction, thereby overcoming the challenges of low substrate solubility and product inhibition. The tested ISPR concept achieved a product concentration of 26.5 gMPPA . L-1 , a purity up to 70% gMPPA . gtot-1 and a recovery in the range of 80% mol . mol-1 of MPPA in 20 h, with the possibility to increase the concentration, purity, and recovery further. Biotechnol. Bioeng. 2017;114: 600 609. (c) 2016 Wiley Periodicals, Inc. PMID- 27668845 TI - Desmoplastic infantile astrocytoma and ganglioglioma: case report and review of the literature. AB - Desmoplastic infantile astrocytoma (DIA) is a rare, supratentorial, dural-based, large cystic tumor that usually arises in the first 24 months of life. However, non-infantile cases were also reported in the literature. Desmoplastic infantile astrocytoma and desmoplastic infantile ganglioglioma (DIG) are both classified as grade I astrocytoma by the World Health Organization (WHO). Grossly, DIA/DIG are large tumors composed of solid and cystic portions. Although large in nature, they are slow-growing tumors, with good prognosis after complete surgical removal, and rarely require a chemotherapy or radiotherapy. However, there have been few cases of DIA that demonstrated malignant features and/or spontaneous recurrence or metastases which necessitates close-up monitoring after surgical intervention. Herein, we report a case of an 18-month-old boy who presented with progressive head enlargement that was discovered to be due to a large left frontal predominantly cystic tumor. The patient underwent subtotal resection (STR) and was diagnosed as DIA on histopathological examination. Over a duration of 18 months of follow-up, the patient's status deteriorated, and he eventually died.?. PMID- 27668844 TI - Sorafenib with ASC-J9(r) synergistically suppresses the HCC progression via altering the pSTAT3-CCL2/Bcl2 signals. AB - Sorafenib is currently used as a standard treatment to suppress the progression of hepatocellular carcinoma (HCC), especially in advanced stages. However, patients who receive Sorafenib treatment eventually develop resistance without clear mechanisms. There is a great need for better efficacy of Sorafenib treatment in combination with other therapies. Here, we demonstrated that the treatment combining Sorafenib with ASC-J9(r) could synergistically suppress HCC progression via altering cell-cycle regulation, apoptosis and invasion. Mechanism dissection suggests that while Sorafenib impacts little or even slightly increases the activated/phosphorylated STAT3 (p-STAT3), a key stimulator to promote the HCC progression, adding ASC-J9(r) significantly suppresses the p STAT3 expression and its downstream genes including CCL2 and Bcl2. Interrupting these signals via constitutively active STAT3 partially reverses the synergistic suppression of Sorafenib-ASC-J9(r) combination on HCC progression. In vivo studies further confirmed the synergistic effect of Sorafenib-ASC-J9(r) combination. Together, these results suggest the newly developed Sorafenib-ASC J9(r) combination is a novel therapy to better suppress HCC progression. PMID- 27668846 TI - Quantifying varus and valgus thrust in individuals with severe knee osteoarthritis. AB - BACKGROUND: Varus-valgus thrust is a biomechanical characteristic linked to knee osteoarthritis disease progression. This study aimed to determine: i) direction of thrust in individuals awaiting total knee arthroplasty versus controls, ii) whether thrust and related parameters differed between groups, iii) differences between osteoarthritis patients awaiting surgery with varus and valgus thrust. METHODS: 44 patients scheduled for surgery and 40 asymptomatic participants were recruited. PRIMARY OUTCOME MEASURES: varus-valgus thrust excursion and absolute thrust magnitude, quantified by 3D gait analysis. FINDINGS: Few differences were found between the osteoarthritis group and controls. The osteoarthritis group as a whole had a more varus knee angle during early- (p<0.0001) and mid-stance (p=0.010) versus controls. The varus thrust osteoarthritis subgroup had a more varus knee angle in overall (p=0.012), early- (p<0.001), and mid- (p<0.001) stance, and a higher peak knee adduction moment (p=0.019) and impulse (p=0.001) when compared to varus thrust controls. No differences were found between the valgus thrust osteoarthritis and control groups. The varus thrust osteoarthritis group had a greater varus peak knee angle in overall (p<0.001), early- (p<0.001), and mid- (p<0.001) stance, higher peak knee adduction moment (p<0.001) and impulse (p=0.001), more varus static alignment (p=0.014), and lower quadriceps strength (p=0.035) than the valgus thrust osteoarthritis group. INTERPRETATION: Those with severe osteoarthritis and a varus thrust have poorer biomechanics, more varus static knee alignment, and lower quadriceps strength compared to those with osteoarthritis with a valgus thrust. Further work is needed to determine if these findings impact total knee arthroplasty outcome. PMID- 27668847 TI - Case fatality models for epidemics in growing populations. AB - The asymptotically homogeneous SIR model of Thieme (1992) for growing populations, with incidence depending in a general way on total population size, is reconsidered with respect to other parameterizations that give clear insight into epidemiological relevant relations and thresholds. One important feature of the present approach is case fatality as opposed to differential mortality. Although case fatality models and differential mortality models are equivalent via a transformation in parameter space, the underlying ideas and the dynamic behaviors are different, e.g. the basic reproduction number depends on differential mortality but not on case fatality. The persistent distributions and exponents of growth of infected solutions are computed and discussed in terms of the parameters. The notion of asymptotically exponentially growing state (as opposed to stationary state or exponential solution) coined by Thieme is interpreted in terms of stability theory. Of some interest are limiting cases of models without recovery where two infected solutions exist. PMID- 27668848 TI - Interactions of infectious F-specific RNA bacteriophages with suspended matter and sediment: Towards an understanding of FRNAPH distribution in a river water system. AB - The association of viruses with settling particles is certainly a major process controlling the spread of viral pollution in surface water and sediment. To better understand the viral distribution in a river system, the behavior of F specific RNA bacteriophages (FRNAPHs) was investigated in relationship with the suspended solids and sediment. The partitioning of phage particles (free or associated with solids) in surface water and the attachment capabilities of eight distinct strains of phages to sediment were studied in lab experiments. In situ observations were also performed with the genotyping of 166 individual plaques of FRNAPHs isolated from surface water and sediment. The results reported here demonstrate a variation of the status of infectious phages as a function of the hydro-climatological conditions. Phage-solid association seems to mainly occur during the peak of rainfall-runoff events but also to a certain extent during the recession phase compared to low flow conditions. The transfer of phages from the water column to sediment may occur at this time. Furthermore, the ability of FRNAPHs to interact with sediment was established for six strains out of eight, belonging to genogroups II, III and IV. A similar dynamic was observed for strains within a same genogroup despite different intensity of attachment and inactivation rates for strains of genogroups III and IV. The latter results match the in situ observations in the water and sediment compartments of the studied area. Infectious FRNAPH genogroup II was more abundant in sediment than in surface water. Its capability to sorb to sediment and its higher persistence in the environment compared to genogroups III and IV were the two main explanations. Together, lab and in situ experiments produce an overall vision of the mechanisms governing FRNAPH distribution among the water column and riverbed sediment. PMID- 27668849 TI - Floristic and vegetation successional processes within landslides in a Mediterranean environment. AB - Floristic and vegetation analysis in seven Mediterranean landslides led to the understanding of the successional processes occurring in different landslide disturbed sectors. Our study showed that in landslides that occurred between 1996 and 2010 there is a clear differentiation between the three main landslide sectors (scarp, main body and foot) concerning floristic composition, vegetation structure, floristic richness, successional processes and plant functional type. Additional differences were found between landslide areas and undisturbed agricultural areas adjacent to landslides. In this study 48 floristic releves were made using a stratified random sampling design. The main landslide body exhibits the highest floristic richness whereas the landslide scarp has the lowest coverage rate and the highest presence of characteristic species from ruderal and strongly perturbed habitats. Finally, the landslide foot shows a late stage in the succession (maquis or pre-forest stage) with a high dominance of vines. We further discuss the importance of landslides as reservoirs of biodiversity especially for Mediterranean orchids. PMID- 27668850 TI - Soil moisture and its role in growth-climate relationships across an aridity gradient in semiarid Pinus halepensis forests. AB - In Mediterranean areas with limited availability of water, an accurate knowledge of growth response to hydrological variables could contribute to improving management and stability of forest resources. The main goal of this study is to assess the temporal dynamic of soil moisture to better understand the water growth relationship of Pinus halepensis forests in semiarid areas. The estimates of modelled soil moisture and measured tree growth were used at four sites dominated by afforested Pinus halepensis Mill. in south-eastern Spain with 300 to 609mm mean annual precipitation. Firstly, dendrochronological samples were extracted and the widths of annual tree rings were measured to compute basal area increments (BAI). Secondly, soil moisture was estimated over 20 hydrological years (1992-2012) by means of the HYDROBAL ecohydrological model. Finally, the tree growth was linked, to mean monthly and seasonal temperature, precipitation and soil moisture. Results depict the effect of soil moisture on growth (BAI) and explain 69-73% of the variance in semiarid forests, but only 51% in the subhumid forests. This highlights the fact that that soil moisture is a suitable and promising variable to explain growth variations of afforested Pinus halepensis in semiarid conditions and useful for guiding adaptation plans to respond pro actively to water-related global challenges. PMID- 27668851 TI - Composition and sources of polycyclic aromatic hydrocarbons in cryoconites of the Tibetan Plateau glaciers. AB - Dark-colored cryoconite can absorb substantial solar radiation, reduce the surface albedo of glaciers, and thus greatly accelerate glacier melting. Organic matters in cryoconites such as polycyclic aromatic hydrocarbons (PAHs) are kind of the light absorbing compositions. In this study, 15 PAHs containing 3-7 rings were identified in 61 cryoconites samples collected from seven glaciers over the Tibetan Plateau (TP). The average concentration of total PAHs in cryoconites samples was in the range of 6.67-3906.66ngg-1 dry weight. The highest average total PAH concentration was found in the southeastern TP, followed by the northern TP. The central TP contained the lowest amount of PAHs. Moreover, correlation analysis showed that total organic carbon (TOC) and grain size were only a minor factor for the accumulation of PAHs in cryoconites of the TP. Factor analysis and diagnostic ratios indicated that the PAHs were produced mainly from the incomplete combustion of coal, fossil fuels and biomasses. The exhaust gas of locomotives also contributed to the accumulation of PAHs in the glaciers. The PAHs in these seven glaciers showed low toxic equivalent quantity (TEQ), and thus had low biological risk. Nevertheless, the pollution of PAHs in the southeastern TP needs to be addressed. PMID- 27668852 TI - Impacts of road network expansion on landscape ecological risk in a megacity, China: A case study of Beijing. AB - Road networks affect the spatial structure of urban landscapes, and with continuous expansion, it will also exert more widespread influences on the regional ecological environment. With the support of geographic information system (GIS) technology, based on the application of various spatial analysis methods, this study analyzed the spatiotemporal changes of road networks and landscape ecological risk in the research area of Beijing to explore the impacts of road network expansion on ecological risk in the urban landscape. The results showed the following: 1) In the dynamic processes of change in the overall landscape pattern, the changing differences in landscape indices of various landscape types were obvious and were primarily related to land-use type. 2) For the changes in a time series, the expansion of the road kernel area was consistent with the extension of the sub-low-risk area in the urban center, but some differences were observed during different stages of development. 3) For the spatial position, the expanding changes in the road kernel area were consistent with the grade changes of the urban central ecological risk, primarily because both had a certain spatial correlation with the expressways. 4) The influence of road network expansion on the ecological risk in the study area had obvious spatial differences, which may be closely associated with the distribution of ecosystem types. PMID- 27668853 TI - 3,4-Dichloroaniline revisited: A study on the fate of the priority pollutant in a sediment-water system derived from a rice growing region in Italy. AB - As ultimate sink for xenobiotics released into the environment, sediments play an important role concerning the evaluation of the fate of foreign compounds. 3,4 Dichloroaniline (3,4-DCA) is a degradation product of herbicide propanil and some urea herbicides. Propanil was extensively used worldwide in rice cultivation. The aim of the study was to examine the fate of 14C-labeled 3,4-DCA in a sediment water system; the sediment was derived from a rice field in Northern Italy. After application of 14C-3,4-DCA, a time-course study was performed using incubation periods from 4h to 56days. Fractions obtained from assays were water phase, sediment phase including methanol and Soxhlet extract as well as non-extractable residues (NER), and mineralized portion (14CO2). Soluble fractions were examined by TLC, HPLC and GC-MS. NER found in sediment phases were further fractionated in non-humics, humic acids, fulvic acids and humin. Stability of systems was checked by microbial activity, dissolved oxygen and pH. After 56days of incubation, 23.1% of applied 14C was mineralized, only 1.30% remained in the water phase, whereas 60.8% was found in the sediment phase, 53.3% of which were NER. Minor metabolites identified were 3,4-dichloroacetanilide (3,4-DCAA) and 3,3',4,4' tetrachloroazobenzene (TCAB; 2.63% after 56days). According to pH, dissolved oxygen and microbial activity, systems appeared to be stable and not influenced by applied 3,4-DCA. Most striking result was the high mineralization rate as compared to previously published data. This finding suggested an adaptation of the microbial community in the sediment possibly due to decade-long treatment of rice fields with propanil. PMID- 27668854 TI - Tropospheric volatile organic compounds in China. AB - Photochemical smog, characterized by high concentrations of ozone (O3) and fine particles (PM2.5) in the atmosphere, has become one of the top environmental concerns in China. Volatile organic compounds (VOCs), one of the key precursors of O3 and secondary organic aerosol (SOA) (an important component of PM2.5), have a critical influence on atmospheric chemistry and subsequently affect regional and global climate. Thus, VOCs have been extensively studied in many cities and regions in China, especially in the North China Plain, the Yangtze River Delta and the Pearl River Delta regions where photochemical smog pollution has become increasingly worse over recent decades. This paper reviews the main studies conducted in China on the characteristics and sources of VOCs, their relationship with O3 and SOA, and their removal technology. This paper also provides an integrated literature review on the formulation and implementation of effective control strategies of VOCs and photochemical smog, as well as suggestions for future directions of VOCs study in China. PMID- 27668855 TI - Automated identification of wound information in clinical notes of patients with heart diseases: Developing and validating a natural language processing application. AB - BACKGROUND: Electronic health records are being increasingly used by nurses with up to 80% of the health data recorded as free text. However, only a few studies have developed nursing-relevant tools that help busy clinicians to identify information they need at the point of care. OBJECTIVE: This study developed and validated one of the first automated natural language processing applications to extract wound information (wound type, pressure ulcer stage, wound size, anatomic location, and wound treatment) from free text clinical notes. METHODS AND DESIGN: First, two human annotators manually reviewed a purposeful training sample (n=360) and random test sample (n=1100) of clinical notes (including 50% discharge summaries and 50% outpatient notes), identified wound cases, and created a gold standard dataset. We then trained and tested our natural language processing system (known as MTERMS) to process the wound information. Finally, we assessed our automated approach by comparing system-generated findings against the gold standard. We also compared the prevalence of wound cases identified from free-text data with coded diagnoses in the structured data. RESULTS: The testing dataset included 101 notes (9.2%) with wound information. The overall system performance was good (F-measure is a compiled measure of system's accuracy=92.7%), with best results for wound treatment (F-measure=95.7%) and poorest results for wound size (F-measure=81.9%). Only 46.5% of wound notes had a structured code for a wound diagnosis. CONCLUSIONS: The natural language processing system achieved good performance on a subset of randomly selected discharge summaries and outpatient notes. In more than half of the wound notes, there were no coded wound diagnoses, which highlight the significance of using natural language processing to enrich clinical decision making. Our future steps will include expansion of the application's information coverage to other relevant wound factors and validation of the model with external data. PMID- 27668856 TI - Tumor microenvironment-mediated chemoresistance in breast cancer. AB - Therapy resistance or tumor relapse in cancer is common. Tumors develop resistance to chemotherapeutic through a variety of mechanisms, with tumor microenvironment (TM) serving pivotal roles. Using breast cancer as a paradigm, we propose that responses of cancer cells to drugs are not exclusively determined by their intrinsic characteristics but are also controlled by deriving signals from TM. Affected microenvironment by chemotherapy is an avenue to promote phenotype which tends to resist on to be ruined. Therefore, exclusively targeting cancer cells does not demolish tumor recurrence after chemotherapy. Regardless of tumor-microenvironment pathways and their profound influence on the responsiveness of treatment, diversity of molecular properties of breast cancer also behave differently in terms of response to chemotherapy. And also it is assumed that there is cross-talk between phenotypic diversity and TM. Collectively, raising complex signal from TM in chemotherapy condition often encourages cancer cells are not killed but strengthen. Here, we summarized how TM modifies responses to chemotherapy in breast cancer. We also discussed successful treatment strategies have been considered TM in breast cancer treatment. PMID- 27668857 TI - The significance of sentinel lymph node micrometastasis in breast cancer: Comparing outcomes with and without axillary clearance. AB - BACKGROUND: Management of micrometastasis in the sentinel node is a controversial topic. Most of the guidelines don't recommend further axillary treatment if micrometastasis are the only finding in the sentinel node. However, some evidence suggests that micrometastasis have significant effect on long term outcomes and therefore indicate systemic treatment. METHOD: Retrospective cohort study reviewing the management of patients with micrometastasis in the sentinel nodes. Two groups were compared, those who had further axillary clearance and those who had not. The primary endpoints were loco-regional recurrence and lymphedema rate. The secondary endpoints were distant metastasis rate, OS and DFS. RESULTS: 95 patients were found to have micrometastasis or ITC in the axillary SNB over a period of 10 years. Of those, 38 patients had axillary clearance after SNB, while 57 did not. Lymphedema rate was 18.4% in the axillary clearance group versus 0% in the no axillary clearance group (p < 0.001). The LRR event was rare therefore not compared. Distant metastasis rate was 7.01% in the SNB group versus 2.6% in the axillary clearance group. There were no mortalities in the axillary clearance group. This compares to 7.01% among the patients who didn't have axillary clearance. All the patients who died had developed distant metastasis as a cause of death. There was a difference in OS between the two groups in favor of the axillary clearance group (p = 0.004). DISCUSSION: Although not an indication for axillary clearance recent guidelines, micrometastasis and ITC found in the SNB are a sign of a biologically different disease. This important information should be taken in consideration when planning the adjuvant treatment in those patients among other factors considered. PMID- 27668858 TI - Safety and outcomes of preoperative embolization of intracranial hemangioblastomas: A systematic review. AB - INTRODUCTION: While preoperative embolization is often reserved for large and highly vascular tumors in order to minimize blood loss, its safety and efficacy in the treatment of hemangioblastomas (HB) is unclear. We present the largest systematic review focusing on the safety and outcome of preoperative embolization of intracranial HB. MATERIALS AND METHODS: To identify all cases of preoperative embolization for HB, a literature search was conducted via Medline (OVID and PubMed), Scopus, Embase, and Web of Science. Studies that were in English, included intracranial hemangioblastomas treated with preoperative embolization and provided sufficient disaggregated clinical data for each patient were included. Historical control patients with non-embolized intracranial HB undergoing resection were similarly identified. RESULTS: A total of 111 patients that underwent preoperative embolization of HB prior to planned resection were identified. Patient age ranged from 12 to 72 years, with a cohort of 63% males and 36% females. Nine studies comprising 392 non-embolized patients were included as controls. Gross total resection was achieved in 83.7% of embolized and 95.6% of non-embolized patients. Intraoperative blood transfusion was required in 15.3% of embolized and 0.51% of non-embolized controls, while rates of post-operative hemorrhage were 8.4% and 1.6%, respectively. Complication rates from embolization were 11.7% and following consequent surgery were 20.7%. DISCUSSION: Embolization did not increase rates of gross total resection, decrease estimated blood loss, or decrease incidence of complications. Not only does embolization fail to mitigate surgical risks, the embolization procedure itself carries significant risk for complications. Embolization should not be standard of care for intracranial HB. PMID- 27668860 TI - Mapping genetic factors in high-grade glioma patients. AB - BACKGROUND: Tumor location, which serves as a prognostic factor for high-grade gliomas, may reflect the molecular and genetic phenotype of tumor initiate cells and thus predict tumor origin. Therefore, the purpose of this study was to combine radiographic atlases and tumor biomarkers through a voxel-based neuroimaging approach. METHODS: Preoperative MRIs were collected from 65 newly diagnosed patients with histologically confirmed high-grades gliomas. These samples were analyzed for TP53 mutations and MMP-9.PTEN, MGMT, EGFR and IDH1 statuses using a statistical voxel-based lesion-symptom mapping (VLSM) method, which correlates the anatomical location of HGGs with their molecular profile. RESULTS: VLSM analysis identified P53, Wild-type IDH and EGFR overexpression mutations in the white matter of the periventricular region in the left hemisphere, which can be predicted by a short overall survival from the time of diagnosis. The lack of MGMT promoter methylation deep in the right frontal lobe region indicates a poor prognosis. CONCLUSIONS: Our study demonstrates that different molecular phenotypes are related to specific brain regions. In addition, the structural MRI and genetic profile-based analysis of brain regions associated with survival-associated factors could be used in planning glioma operations and clinical survival predictions. PMID- 27668859 TI - Evaluation of median nerve T2 signal changes in patients with surgically treated carpal tunnel syndrome. AB - OBJECTIVE: To determine the accuracy of median nerve T2 evaluation and its relation with Boston Questionnaire (BQ) and nerve conduction studies (NCSs) in pre-operative and post-operative carpal tunnel syndrome (CTS) patients in comparison with healthy volunteers. METHODS: Twenty-three CTS patients and 24 healthy volunteers underwent NCSs, median nerve T2 evaluation and self administered BQ. Pre-operative and 1st year post-operative median nerve T2 values and cross-sectional areas (CSAs) were compared both within pre-operative and post operative CTS groups, and with healthy volunteers. The relationship between MRI findings and BQ and NCSs was analyzed. The ROC curve analysis was used for determining the accuracy. RESULTS: The comparison of pre-operative and post operative T2 values and CSAs revealed statistically significant improvements in the post-operative patient group (p<0.001 for all parameters). There were positive correlations between T2 values at all levels and BQ values, and positive and negative correlations were also found regarding T2 values and NCS findings in CTS patients. The receiver operating characteristic curve analysis for defined cut-off levels of median nerve T2 values in hands with severe CTS yielded excellent accuracy at all levels. However, this accuracy could not be demonstrated in hands with mild CTS. CONCLUSION: This study is the first to analyze T2 values in both pre-operative and post-operative CTS patients. The presence of increased T2 values in CTS patients compared to controls and excellent accuracy in hands with severe CTS indicates T2 signal changes related to CTS pathophysiology and possible utilization of T2 signal evaluation in hands with severe CTS. PMID- 27668861 TI - Drinking to Cope With Depressive Symptoms and Ruminative Thinking: A Multiple Mediation Model Among College Students. AB - BACKGROUND: Understanding the potential psychosocial mechanisms that explain (i.e., mediate) the associations between depressive symptoms and alcohol-related problems can improve interventions targeting college students. OBJECTIVES: The current research examined four distinct facets of rumination (e.g., problem focused thoughts, counterfactual thinking, repetitive thoughts, and anticipatory thoughts) and drinking to cope motives as potential explanatory mechanisms by which depressive symptoms are associated with increased alcohol-related problems. METHOD: Participants were undergraduate students from a large, southeastern university in the United States that consumed at least one drink per typical week in the previous month (n = 403). The majority of participants were female (n = 291; 72.2%), identified as being either White, non-Hispanic (n = 210; 52.1%), or African American (n = 110; 27.3%), and reported a mean age of 21.92 (SD = 5.75) years. RESULTS: Structural equation modeling was conducted examining the concurrent associations between depressive symptoms, rumination facets, drinking to cope motives, and alcohol-related problems (i.e., cross-sectional). There was one significant double-mediated association that suggested that increased depressive symptoms is associated with increased problem-focused thoughts, which is associated with higher drinking to cope motives and alcohol-related problems. Conclusions/Importance: Our results suggests that problem-focused thoughts at least partially explains the associations between depression and maladaptive coping (i.e., drinking to cope), which in turn is related to problematic drinking among college students. Limitations and future directions are discussed. PMID- 27668862 TI - A High-Resolution Magic Angle Spinning NMR Study of the Enantiodiscrimination of 3,4-Methylenedioxymethamphetamine (MDMA) by an Immobilized Polysaccharide-Based Chiral Phase. AB - This paper reports the investigation of the chiral interaction between 3,4 methylenedioxy-methamphetamine (MDMA) enantiomers and an immobilized polysaccharide-based chiral phase. For that, suspended-state high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (1H HR-MAS NMR) was used. 1H HR-MAS longitudinal relaxation time and Saturation Transfer Difference (STD NMR) titration experiments were carried out yielding information at the molecular level of the transient diastereoisomeric complexes of MDMA enantiomers and the chiral stationary phase. The interaction of the enantiomers takes place through the aromatic moiety of MDMA and the aromatic group of the chiral selector by pi-pi stacking for both enantiomers; however, a stronger interaction was observed for the (R)-enantiomer, which is the second one to elute at the chromatographic conditions. PMID- 27668863 TI - The Effects of Lack of Joint Goal Planning on Divorce over 10 Years. AB - Given the negative consequences of divorce on health and well-being, it is important to try to identify its predictors. In the current study we used data from the National Survey of Midlife Development (N = 2801) to examine the longitudinal effects of lack of joint goal planning with a romantic relationship partner on divorce over a 10-year period. Multilevel regression analyses showed that lack of joint planning with the relationship partner was associated with a 19% increase in the odds of divorce, even when controlling for various demographic (i.e., age, gender, relationship length, number of children in the household), individual (i.e., neuroticism, positive affect, negative affect, physical symptoms, planning), and relationship (i.e., marital empathy, partner strain, partner disagreement, marital satisfaction, commitment). These results demonstrate the importance of considering one's partner when making decisions and plans for the future, given that it has clear implications for relationship dissolution. PMID- 27668864 TI - Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury. AB - BACKGROUND: Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. METHODS AND FINDINGS: Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (gamma) subunit of acetylcholine receptor (gamma-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. gamma-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, gammaAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli. CONCLUSIONS: Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest indices including satellite cell responsiveness, atrogin-1, atrophy, and innervation may predict surgical outcome. PMID- 27668865 TI - Tcf7l2/Tcf4 Transcriptional Repressor Function Requires HDAC Activity in the Developing Vertebrate CNS. AB - The generation of functionally distinct neuronal subtypes within the vertebrate central nervous system (CNS) requires the precise regulation of progenitor gene expression in specific neuronal territories during early embryogenesis. Accumulating evidence has implicated histone deacetylase (HDAC) proteins in cell specification, proliferation, and differentiation in diverse embryonic and adult tissues. However, although HDAC proteins have shown to be expressed in the developing vertebrate neural tube, their specific role in CNS neural progenitor fate specification remains unclear. Prior work from our lab showed that the Tcf7l2/Tcf4 transcription factor plays a key role in ventral progenitor lineage segregation by differential repression of two key specification factors, Nkx2.2 and Olig2. In this study, we found that administration of HDAC inhibitors (Valproic Acid (VPA), Trichostatin-A (TSA), or sodium butyrate) in chick embryos in ovo disrupted normal progenitor gene segregation in the developing neural tube, indicating that HDAC activity is required for this process. Further, using functional and pharmacological approaches in vivo, we found that HDAC activity is required for the differential repression of Nkx2.2 and Olig2 by Tcf7l2/Tcf4. Finally, using dominant-negative functional assays, we provide evidence that Tcf7l2/Tcf4 repression also requires Gro/TLE/Grg co-repressor factors. Together, our data support a model where the transcriptional repressor activity of Tcf7l2/Tcf4 involves functional interactions with both HDAC and Gro/TLE/Grg co factors at specific target gene regulatory elements in the developing neural tube, and that this activity is required for the proper segregation of the Nkx2.2 (p3) and Olig2 (pMN) expressing cells from a common progenitor pool. PMID- 27668867 TI - An Editor's Farewell. PMID- 27668866 TI - SNP-SNP Interaction Analysis on Soybean Oil Content under Multi-Environments. AB - Soybean oil content is one of main quality traits. In this study, we used the multifactor dimensionality reduction (MDR) method and a soybean high-density genetic map including 5,308 markers to identify stable single nucleotide polymorphism (SNP)-SNP interactions controlling oil content in soybean across 23 environments. In total, 36,442,756 SNP-SNP interaction pairs were detected, 1865 of all interaction pairs associated with soybean oil content were identified under multiple environments by the Bonferroni correction with p <3.55*10-11. Two and 1863 SNP-SNP interaction pairs detected stable across 12 and 11 environments, respectively, which account around 50% of total environments. Epistasis values and contribution rates of stable interaction (the SNP interaction pairs were detected in more than 2 environments) pairs were detected by the two way ANOVA test, the available interaction pairs were ranged 0.01 to 0.89 and from 0.01 to 0.85, respectively. Some of one side of the interaction pairs were identified with previously research as a major QTL without epistasis effects. The results of this study provide insights into the genetic architecture of soybean oil content and can serve as a basis for marker-assisted selection breeding. PMID- 27668868 TI - Longitudinal Changes in Refractive Error in a Pediatric Referral Population in Korea. AB - PURPOSE: To investigate changes in the spherical equivalent (SE) refractive error and astigmatism in a pediatric referral population in Korea with longitudinal follow-up and to evaluate the effect of risk factors on changes in refractive error. METHODS: This was a retrospective case series. In total, 221 patients who presented to a tertiary care hospital when aged 3 to 9 years and who underwent at least 10 years of follow-up were enrolled. The patients were divided into groups in terms of the initial extent of SE refractive error, the initial extent of astigmatism, sex, and ocular alignment. Changes in SE and astigmatism were compared among the groups. RESULTS: The patients were followed up for a mean of 11.19 +/- 1.81 years. An overall negative shift in SE refractive error and increasing tendency in astigmatism during the follow-up period were noted. The negative shift in SE refractive error in the myopia group was significantly greater than those in the emmetropia and hyperopia groups. The change in astigmatism in the myopia group was significantly greater than that in the hyperopia group. The change in astigmatism in the low astigmatism group was significantly greater than those in the moderate and high astigmatism groups. Sex did not influence the changes in SE refractive error or astigmatism. CONCLUSIONS: A pediatric referral population in Korea showed a negative shift in SE refractive error and increasing tendency in astigmatism during childhood. Changes in refractive error may be influenced by the initial degree of SE refractive error and astigmatism. [J Pediatr Ophthalmol Strabismus. 2017;54(1):43-51.]. PMID- 27668869 TI - Visual, Topographic, and Pachymetric Effects of Pediatric Corneal Collagen Cross linking. AB - PURPOSE: To evaluate the effects of pediatric corneal collagen cross-linking (CXL) on corrected distance visual acuity (CDVA), maximum keratometry (Kmax), and other Scheimpflug imaging system parameters during 2 years of follow-up. METHODS: The records of 29 eyes of 29 pediatric patients who underwent unilateral CXL treatment for progressive keratoconus were reviewed. Changes in CDVA, Kmax, anterior chamber depth, anterior chamber volume, anterior chamber angle, pupil center pachymetry, apical pachymetry, thinnest pachymetry, corneal volume, and topographic indices (index of surface variance [ISV], index of vertical asymmetry [IVA], index of height asymmetry [IHA], keratoconus index [KI], center keratoconus index [CKI], index of height decentration [IHD], and minimum radius of curvature [Rmin]) were analyzed among baseline and 1 and 2 years after the CXL treatment. RESULTS: Mean CDVA and Kmax significantly improved from baseline at 1 year (-0.17 logMAR, P < .0001; -1.18 diopters [D], P = .012, respectively) and 2 years (-0.21 logMAR, P < .0001; -1.40 D, P = .001, respectively) after the CXL treatment. Anterior chamber parameters, corneal thicknesses, and corneal volume remained unchanged during the period following CXL (P > .05). Five of the seven Scheimpflug topographic indices (including ISV, KI, CKI, IHD, and Rmin) showed significant improvement after CXL between baseline and 2 years (P < .05). CONCLUSIONS: In pediatric patients with progressive keratoconus, CXL appears to be effective in improving CDVA, Kmax, and corneal topographic irregularity at 2 years' follow-up. However, long-term effects of CXL should be tested by further studies in pediatric keratoconus. [J Pediatr Ophthalmol Strabismus. 2017;54(2):84 89.]. PMID- 27668870 TI - Comparison of Pediatric and Adult Ophthalmology Consultations in an Urban Academic Medical Center. AB - PURPOSE: The purpose of this study was to compare pediatric and adult ophthalmology consultations in an urban academic center. METHODS: A retrospective chart review of patients evaluated by the ophthalmology consultation service from January through June 2014 was conducted. RESULTS: A total of 751 inpatients and emergency department patients were evaluated by the ophthalmology consultation service, of whom 152 (20.4%) were children and 598 (79.6%) were adults. The emergency department requested most of these consultations (42.8%), followed by internal medicine (39.1%) and pediatrics (18.4%) inpatients. More adult patients (94.5%) than children (76.5%) had abnormal findings on examination (P < .001). Altering management was recommended at a similar rate: 51.6% of pediatric patients and 54.3% of adult patients (P = .59). All children were initially seen by residents; children (38.6%) were more likely than adults (9.0%) to be seen with an attending physician (P < .001). Children (54.9%) were also more likely than adults (42.7%) to attend their recommended outpatient appointments (P = .027). CONCLUSIONS: The authors identified several interesting differences between the pediatric and adult consultation services. Although adult patients were more likely to have abnormal findings, the ophthalmology team recommended a change in management for more than half of each group. These rates of intervention suggest that it is equally important that children be considered for an ophthalmology consultation and examined as soon as possible. In addition, residents may need particular guidance in evaluating pediatric inpatients. [J Pediatr Ophthalmol Strabimus. 2017;54(1):17-21.]. PMID- 27668871 TI - Management of Pediatric Aphakic Glaucoma With Vitrectomy and Tube Shunts. AB - PURPOSE: To review the impact of vitrectomy and tube shunts on mean intraocular pressure (IOP) and number of glaucoma medications in pediatric aphakic glaucoma. METHODS: A retrospective review of pediatric patients who underwent combined vitrectomy and glaucoma tube shunt surgery for aphakic glaucoma was conducted. Inclusion criteria were: age 18 years or younger, diagnosis of aphakic glaucoma, preoperative IOP data, and postoperative IOP data for at least 6 months. Mean IOP lowering at 1 year, number of glaucoma medications at 1 year, and surgical complications, including tube occlusion in the postoperative period, were noted. RESULTS: The mean +/- standard deviation preoperative IOP was 33.9 +/- 10.6 mm Hg (range: 18 to 57 mm Hg) with a mean of three topical IOP-lowering medications. A total of 5 (36%) Ahmed and 9 (64%) Baerveldt tube shunts were placed. One of the Baerveldt tube shunt procedures was combined with revision of a traumatically dislocated tube. The mean IOP at 12 months postoperatively was 16.6 +/- 5.8 mm Hg (range: 6 to 28 mm Hg; P < .01, t = 3.74, df = 13) with a mean of 2.3 glaucoma medications. There were no cases of tube occlusion, corneal decompensation, endophthalmitis, or retinal detachment over the 12 months of follow-up. CONCLUSIONS: Combined vitrectomy and placement of a glaucoma tube shunt can be safe and effective in lowering IOP based on mean IOP values and number of glaucoma medications at 1 year. [J Pediatr Ophthalmol Strabismus. 2016;53(6):339 343.]. PMID- 27668872 TI - Ophthalmologic Outcomes of Children Born Premature Without ROP: Correlations With Gestational Age and Psychomotor Development. AB - PURPOSE: To study ophthalmological outcomes of premature children with no retinopathy of prematurity (ROP) and correlate with neurodevelopmental outcomes. METHODS: A total of 69 former preterm infants were evaluated at 2 to 7 years of age. Detailed ophthalmologic examinations were performed. Neurodevelopment was assessed using the Peabody Developmental Motor Scale and Wechsler Preschool and Primary Scale of Intelligence. Another 69 healthy children served as controls. RESULTS: The 69 preterm children (38 of 69 boys) and 69 controls (38 of 69 boys) had a mean age of 4.9 +/- 1.5 and 4.9 +/- 1.4 years, respectively. Compared to controls, preterm infants had vision impairment of 19% versus 1.4% (P = .001), hyperopia of 87% versus 98.5% (P = .21), myopia of 11% versus 1.4% (P = .017), and astigmatism of 39% versus 30.4% (P = .37). Children with any motor disability tended to have worse vision. CONCLUSIONS: In the absence of ROP, hyperopia was more common in infants 32 weeks or older who weighed more than 1,500 g at birth; other vision problems were similar in subgroups. This may represent impending myopia in those younger than 32 weeks weighing less than 1,500 g. [J Pediatr Ophthalmol Strabismus. 2017;54(1):32-38.]. PMID- 27668873 TI - Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression. AB - The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non self discrimination in the immune system and a possible strategy for its experimental verification. PMID- 27668875 TI - Beverages Sales in Mexico before and after Implementation of a Sugar Sweetened Beverage Tax. AB - OBJECTIVE: To estimate changes in sales of sugar sweetened beverages (SSB) and plain water after a 1 peso per liter excise SSB tax was implemented in Mexico in January 2014. MATERIAL AND METHODS: We used sales data from the Monthly Surveys of the Manufacturing Industry from January 2007 to December 2015. We estimated Ordinary Least Squares models to assess changes in per capita sales of SSB and plain water adjusting for seasonality and the global indicator of economic activity. RESULTS: We found a decrease of 7.3% in per capita sales of SSB and an increase of 5.2% of per capita sales of plain water in 2014-2015 compared to the pre-tax period (2007-2013). CONCLUSIONS: Adjusting for variables that change over time and that are associated with the demand for SSB, we found the tax was associated with a reduction in per capita sales of SSB. The effectiveness of the tax should be evaluated in the medium and long term. PMID- 27668874 TI - Global Analysis of Type Three Secretion System and Quorum Sensing Inhibition of Pseudomonas savastanoi by Polyphenols Extracts from Vegetable Residues. AB - Protection of plants against bacterial diseases still mainly relies on the use of chemical pesticides, which in Europe correspond essentially to copper-based compounds. However, recently plant diseases control is oriented towards a rational use of molecules and extracts, generally with natural origin, with lower intrinsic toxicity and a reduced negative environmental impact. In this work, polyphenolic extracts from vegetable no food/feed residues of typical Mediterranean crops, as Olea europaea, Cynara scolymus, and Vitis vinifera were obtained and their inhibitory activity on the Type Three Secretion System (TTSS) and the Quorum Sensing (QS) of the Gram-negative phytopathogenic bacterium Pseudomonas savastanoi pv. nerii strain Psn23 was assessed. Extract from green tea (Camellia sinensis) was used as a positive control. Collectively, the data obtained through gfp-promoter fusion system and real-time PCR show that all the polyphenolic extracts here studied have a high inhibitory activity on both the TTSS and QS of Psn23, without any depressing effect on bacterial viability. Extracts from green tea and grape seeds were shown to be the most active. Such activity was confirmed in planta by a strong reduction in the ability of Psn23 to develop hyperplastic galls on explants from adult oleander plants, as well as to elicit hypersensitive response on tobacco. By using a newly developed Congo red assay and an ELISA test, we demonstrated that the TTSS-targeted activity of these polyphenolic extracts also affects the TTSS pilus assembly. In consideration of the potential application of polyphenolic extracts in plant protection, the absence of any toxicity of these polyphenolic compounds was also assessed. A widely and evolutionary conserved molecular target such as Ca2+-ATPase, essential for the survival of any living organism, was used for the toxicity assessment. PMID- 27668876 TI - Biochemical compositions and fatty acid profiles in four species of microalgae cultivated on household sewage and agro-industrial residues. AB - The potential of four regional microalgae species was evaluated in relation to their cell growth and biomass production when cultured in the following alternative media: bio-composts of fruit/horticultural wastes (HB), sugarcane waste and vinasse (VB) chicken excrements (BCE), raw chicken manure (RCM), and municipal domestic sewage (MDS). The cultures were maintained under controlled conditions and their growth responses, productivities, biochemical compositions, and the ester profiles of their biomasses were compared to the results obtained in the synthetic media. The MDS and HB media demonstrated promising results for cultivation, especially of Chlorella sp., Chlamydomonas sp., and Lagerheimia longiseta, which demonstrated productivities superior to those seen when grown on the control media. The highest lipid levels were obtained with the HB medium. The data obtained demonstrated the viability of cultivating microalgae and producing biomass in alternative media prepared from MDS and HB effluents to produce biodiesel. PMID- 27668877 TI - Ensiling characteristics, structural and nonstructural carbohydrate composition and enzymatic digestibility of Napier grass ensiled with additives. AB - Ensiling characteristics, structural and nonstructural carbohydrate composition and enzymatic digestibility (ED) of Napier grass silage was examined. Napier grass ensiled with no additive control, 0.2% formic acid, 0.4% molasses, and 0.3% fibrolytic enzyme for, 7, 30, 60 and 90days. Additives increased lactic acid, soluble carbohydrate and decreased all of lignocellulosic contents except acid detergent lignin and pH than control. The highest value of nonstructural carbohydrate and large reduction in lignocellulosic contents was observed in formic acid and fibrolytic enzyme silage respectively. The content of glucose and fructose showed rapid drop in the first 7days of ensilage. Ensilage decreased lignocellulosic contents and increased ED compared to fresh material. The ED of formic acid and molasses silage was significantly higher than control and fibrolytic enzyme silages in all tested days. In summery the ensiling quality structural and nonstructural carbohydrate and ED value of mature Napier grass silage improved through additives. PMID- 27668878 TI - Microalgal biomass generation by phycoremediation of dairy industry wastewater: An integrated approach towards sustainable biofuel production. AB - Dairy wastewater collected from local dairy industry was used as a growth media (without any pre-treatment) for the cultivation of microalgae Acutodesmus dimorphus. The level of COD reduced over 90% (from 2593.33+/-277.37 to 215+/ 7.07mg/L) after 4days of cultivation; whereas, ammoniacal nitrogen was consumed completely (277.4+/-10.75mg/L) after 6days of cultivation. Dry biomass of 840 and 790mg/L was observed after 4 and 8days of cultivation, respectively, which is about 5-6 times more than that of BG-11 grown culture (149mg/L after 8days). This biomass contains around 25% lipid and 30% carbohydrate, which can be further converted into biodiesel and bioethanol, respectively. Theoretical calculations based on the recently reported conversion yield suggest that 1kg biomass of A. dimorphus might produce around 195g of biodiesel and 78g of bioethanol, which sums up to 273g of biofuels. PMID- 27668879 TI - Enhancement of high-solids enzymatic hydrolysis of corncob residues by bisulfite pretreatment for biorefinery. AB - Co-production of glucose, furfural and other green materials based on a lignocellulosic biorefinery is a promising way to realize the commercial application of corncob residues. An effective process was developed for glucose production using low temperature bisulfite pretreatment and high-solids enzymatic hydrolysis. Corncob residues from furfural production (FRs) were pretreated with 0.1g NaHSO3/g dry substrate at 100 degrees C for 3h. Lignin was sulfonated and sulfonic groups were produced during pretreatment, which resulted in decreasing the zeta potential of the samples. Compared with raw material, bisulfite pretreatment of FRs increased the glucose yield from 18.6 to 99.45% after 72h hydrolysis at a solids loading of 12.5%. The hydrolysis residues showed a relatively high thermal stability and concentrated high derivatives. Direct pretreatment followed by enzymatic hydrolysis is an environmentally-friendly and economically-feasible method for the production of glucose and high-purity lignin, which could be further converted into high-value products. PMID- 27668880 TI - Valorization of sugar-to-ethanol process waste vinasse: A novel biorefinery approach using edible ascomycetes filamentous fungi. AB - The aim of the present work was to study the integration of edible ascomycetes filamentous fungi into the existing sugar- or molasses-to-ethanol processes, to grow on vinasse or stillage and produce ethanol and protein-rich fungal biomass. Two fungal strains, Neurospora intermedia and Aspergillus oryzae were examined in shake flasks and airlift-bioreactors, resulting in reduction of vinasse COD by 34% and viscosity by 21%. Utilization of glycerol and sugars were observed, yielding 202.4 or 222.8g dry fungal biomass of N. intermedia or A. oryzae respectively, per liter of vinasse. Integration of the current process at an existing ethanol facility producing about 100,000m3 of ethanol per year could produce around 200,000-250,000tons of dry fungal biomass (40-45% protein) together with about 8800-12,600m3 extra ethanol (8.8-12.6% of production-rate improvement). PMID- 27668881 TI - Hydrothermal liquefaction of Undaria pinnatifida residues to organic acids with recyclable trimethylamine. AB - This study investigated the effect of trimethylamine (TMA) on the hydrothermal liquefaction (HTL) process and the recycle of TMA. The results suggest that the peeling reaction occurred on the surface and the cleavage of cellulose leading to water-soluble substances and bio-oil. The highest content of organic acids was found in the water-soluble phase. Model compounds, different glucides with TMA were used to investigate the mechanism of the HTL. Results suggest that the OH- appeared to selectively interact with C-O-C bonds, and thus causing the key linkages of cellulose to become much easier to be cleaved under mild conditions. In addition, the conditions for TMA recovery were optimized and the highest TMA recovery rate reached 98.89%. The recovered TMA had the same properties as the original compound, and it was perfectly re-usable in the conversion process of HTL. PMID- 27668882 TI - The Association of CXC Receptor 4 Mediated Signaling Pathway with Oxaliplatin Resistant Human Colorectal Cancer Cells. AB - The stromal cell-derived factor-1 (SDF-1)/CXC receptor 4 (CXCR4) axis plays an important role in tumor angiogenesis and invasiveness in colorectal cancer (CRC) progression. In addition, metastatic CRC remains one of the most difficult human malignancies to treat because of its chemoresistant behavior. However, the mechanism by which correlation occurs between CXCR4 and the clinical response of CRC to chemotherapy remains unknown. We generated chemoresistant cells with increasing doses of oxaliplatin (OXA) and 5-Fluorouracil (5FU) to develop resistance at a clinical dose. We found that the putative markers did not change in the parental cells, but HCT-116/OxR and HCT-116/5-FUR were more aggressive and had higher tumor growth (demonstrated by wound healing, chemotaxis assay, and a nude mice xenograft model) with the use of oxaliplatin. Apoptosis induced by oxaliplatin treatment was significantly decreased in HCT-116/OxR compared to the parental cells. Moreover, HCT-116/OxR cells displayed increased levels of p-gp, p Akt p-ERK, p-IKBbeta, CXCR4, and Bcl-2, but they also significantly inhibited the apoptotic pathways when compared to the parental strain. We evaluated the molecular mechanism governing the signaling pathway associated with anti apoptosis activity and the aggressive status of chemoresistant cells. Experiments involving specific inhibitors demonstrated that the activation of the pathways associated with CXCR4, ERK1/2 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/Akt is critical to the functioning of the HCT-116/OxR and HCT-116/5-FUR characteristics of chemosensitivity. These findings elucidate the mechanism of CXCR4/PI3K/Akt downstream signaling and provide strategies to inhibit CXCR4 mediated signaling pathway in order to overcome CRC's resistance to chemotherapy. PMID- 27668883 TI - The Validity and Reliability of the Mini-Mental State Examination-2 for Detecting Mild Cognitive Impairment and Alzheimer's Disease in a Korean Population. AB - OBJECTIVE: To examine the validity and reliability of the MMSE-2 for assessing patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in a Korean population. Specifically, the usefulness of the MMSE-2 as a screening measure for detecting early cognitive change, which has not been detectable through the MMSE, was examined. METHODS: Two-hundred and twenty-six patients with MCI, 97 patients with AD, and 91 healthy older adults were recruited. All participants consented to examination with the MMSE-2, the MMSE, and other detailed neuropsychological assessments. RESULTS: The MMSE-2 performed well in discriminating participants across Clinical Dementia Rating (CDR) stages and CDR Sum of Boxes (CDR-SOB), and it showed excellent internal consistency, high test retest reliability, high interrater reliability, and good concurrent validity with the MMSE and other detailed neuropsychological assessments. The MMSE-2 was divided into two factors (tests that are sensitive to decline in cognitive functions vs. tests that are not sensitive to decline in cognitive functions) in normal cognitive aging. Moreover, the MMSE-2 was divided into two factors (tests related overall cognitive functioning other than memory vs. tests related to episodic memory) in patients with AD. Finally, the MMSE-2 was divided into three factors (tests related to working memory and frontal lobe functioning vs. tests related to verbal memory vs. tests related to orientation and immediate recall) in patients with MCI. The sensitivity and specificity of the three versions of the MMSE-2 were relatively high in discriminating participants with normal cognitive aging from patients with MCI and AD. CONCLUSION: The MMSE-2 is a valid and reliable cognitive screening instrument for assessing cognitive impairment in a Korean population, but its ability to distinguish patients with MCI from those with normal cognitive aging may not be as highly sensitive as expected. PMID- 27668884 TI - Expression analysis of fertilization/early embryogenesis-associated genes in Phalaenopsis orchids. AB - One of the distinct reproductive programs in orchid species is pollination triggered ovule development and megasporogenesis. During sexual reproduction, fertilization occurs days to months after pollination. The molecular mechanisms evolved to carry out this strategic reproductive program remain unclear. In the August issue of Plant Physiology 1 , we report comprehensive studies of comparative genome-wide gene expression in various reproductive tissues and the molecular events associated with developmental transitions unique to sexual reproduction of Phalaenopsis aphrodite. Transcriptional factors and signaling components whose expression is specifically enriched in interior ovary tissues when fertilization occurs and embryos start to develop have been identified. Here, we report verification of additional fertilization-associated genes, DOMAINS REARRANGED METHYLTRANSFERASE 1 (PaDRM1), CHROMOMETHYLTRANSFERASE 1 (PaCMT1), SU(VAR)3-9 RELATED PROTEIN 1 (PaSUVR1), INDOLE-3-ACETIC ACID inducible 30-like 1 (PaIAA30L1), and ETHYLENE INSENSITIVE 3-like 1 (PaEIN3L1), and discuss their potential roles in gametophyte development, epigenetic reprogramming, and hormone regulation during fertilization and establishment of embryo development in Phalaenopsis orchids. PMID- 27668885 TI - A mechanistic approach to explore novel HDAC1 inhibitor using pharmacophore modeling, 3D- QSAR analysis, molecular docking, density functional and molecular dynamics simulation study. AB - Deregulated epigenetic activity of Histone deacetylase 1 (HDAC1) in tumor development and carcinogenesis pronounces it as promising therapeutic target for cancer treatment. HDAC1 has recently captured the attention of researchers owing to its decisive role in multiple types of cancer. In the present study a multistep framework combining ligand based 3D-QSAR, molecular docking and Molecular Dynamics (MD) simulation studies were performed to explore potential compound with good HDAC1 binding affinity. Four different pharmacophore hypotheses Hypo1 (AADR), Hypo2 (AAAH), Hypo3 (AAAR) and Hypo4 (ADDR) were obtained. The hypothesis Hypo1 (AADR) with two hydrogen bond acceptors (A), one hydrogen bond donor (D) and one aromatics ring (R) was selected to build 3D-QSAR model on the basis of statistical parameter. The pharmacophore hypothesis produced a statistically significant QSAR model, with co-efficient of correlation r2=0.82 and cross validation correlation co-efficient q2=0.70. External validation result displays high predictive power with r2 (o) value of 0.88 and r2 (m) value of 0.58 to carry out further in silico studies. Virtual screening result shows ZINC70450932 as the most promising lead where HDAC1 interacts with residues Asp99, His178, Tyr204, Phe205 and Leu271 forming seven hydrogen bonds. A high docking score (-11.17kcal/mol) and lower docking energy -37.84kcal/mol) displays the binding efficiency of the ligand. Binding free energy calculation was done using MM/GBSA to access affinity of ligands towards protein. Density Functional Theory was employed to explore electronic features of the ligands describing intramolcular charge transfer reaction. Molecular dynamics simulation studies at 50ns display metal ion (Zn)-ligand interaction which is vital to inhibit the enzymatic activity of the protein. PMID- 27668886 TI - Long time immunogenicity of measles vaccine in the vaccination era: An open question. AB - After WHO European Region determined the 2005 - 2010 Strategic Plan for measles elimination, the number of reported measles cases in Europe fell dramatically. This decrease is related to the vaccination strategy carried out by European countries. This extensive immunization strategy changes the epidemiological patter and could influence the effectiveness and the long-time immunogenicity of the vaccine. To evaluate the long-time immunogenicity of the measles vaccine in the vaccination era, a pilot study among vaccinated blood donors in Apulia was designed. Of 174 enrolled patients, 93.7% presented an anti-measles IgG titer positive. GMT seems to increase by age (p = 0.001). The GMT seems to increase by age and this could be related to the exposition to natural boosters, that was more probable before the beginning of universal mass vaccination against measles. Future studies have to focus the correlation between GMT and age. PMID- 27668887 TI - Achieving protection against HBV in HIV patients: Finding the best strategy. AB - HBV and HIV coinfection is common and entails important morbi-mortality. Vaccination and anti-HBs seroconvertion is a desirable goal in HIV infected patients. New strategies are necessary to predict seroconversion and clinical endpoints. More studies, in the subgroup of HIV patients with poor immunovirological status are needed. PMID- 27668888 TI - Racial Differences in Mortality from Severe Acute Respiratory Failure in the United States, 2008-2012. AB - RATIONALE: Racial disparities in health and healthcare in the United States are well documented and are increasingly recognized in acute critical illnesses such as sepsis and acute respiratory failure. OBJECTIVES: Using a large, representative, U.S. nationwide database, we examined the hypothesis that black and Hispanic patients with severe acute respiratory failure have higher mortality rates when compared with non-Hispanic whites. METHODS: This retrospective analysis used discharge data from the Agency for Healthcare Research and Quality, Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, for the years 2008-2012. We identified hospitalizations with acute respiratory failure using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification, codes. A logistic regression model was fitted to compare in-hospital mortality rates by race. MEASUREMENTS AND MAIN RESULTS: After adjusting for sex, age, race, disease severity, type of hospital, and median household income for patient ZIP code, blacks had a greater odds ratio of in hospital death when compared with non-Hispanic whites (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.11-1.14; P < 0.001), and Hispanics also had a greater odds ratio of in-hospital death when compared with non-Hispanic whites (OR, 1.17; 95% CI, 1.15-1.19; P < 0.001), and so did Asian and Pacific Islanders (OR, 1.15; 95% CI, 1.12-1.18; P < 0.001) and Native Americans (OR, 1.08; 95% CI, 1.00-1.15; P < 0.001) when compared with non-Hispanic whites (OR, 1.0). CONCLUSIONS: Blacks, Hispanics, and other racial minorities in the United States were observed to exhibit significantly higher in-hospital sepsis-related respiratory failure associated mortality when compared with non-Hispanic whites. PMID- 27668891 TI - Interventions to encourage uptake of cancer screening for people with severe mental illness. AB - BACKGROUND: Adults with severe mental illness (i.e. schizophrenia or other related psychotic disorders and bipolar disorder) can be at greater risk of cancer than those without severe mental illness (SMI). Early detection of cancer through screening is effective in improving patient outcomes including death. However, people with SMI are less likely than others to take up available cancer screening. OBJECTIVES: To determine the effectiveness of interventions targeted at adults with SMI, or their carers or health professionals, and aimed at increasing the uptake of cancer screening tests for which the adults with SMI are eligible. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (October 25, 2012; December 19, 2014; April 07, 2015; July 04, 2016). SELECTION CRITERIA: All randomised controlled trials (RCTs) of interventions, targeted towards adults with SMI or their carers or health professionals, to encourage uptake of cancer screening tests for which the adults with SMI were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and assessed these against the inclusion criteria. MAIN RESULTS: We did not find any trials that met the inclusion criteria. AUTHORS' CONCLUSIONS: A comprehensive search showed that currently there is no RCT evidence for any method of encouraging cancer screening uptake in people with SMI. No specific approach can therefore be recommended. High-quality, large-scale RCTs are needed urgently to help address the disparity between people with SMI and others in cancer screening uptake. PMID- 27668889 TI - MiR-139-5p is associated with inflammatory regulation through c-FOS suppression, and contributes to the progression of primary biliary cholangitis. AB - Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized pathologically by destruction of intrahepatic bile ducts. PBC is largely classified into three subtypes based on clinical course: (i) gradually progressive, (ii) portal hypertension, and (iii) hepatic failure. Previous studies have indicated that serum levels of the pro-inflammatory cytokine TNF alpha, is elevated in PBC patients with fibrosis. Although the severity of cholangitis might also be related to the PBC subtype, its etiology has been unclear. Several studies have shown that microRNAs (miRNAs) demonstrate specific expression patterns in various diseases. In the present study, we evaluated miRNA expression patterns among the PBC subtypes using comprehensive deep sequencing. We also carried out histologic examination by laser capture microdissection and investigated how the identified miRNAs were involved in PBC clinical progression using the miRNA transfection method. On average, ~11 million 32-mer short RNA reads per sample were obtained, and we found that the expression levels of 97 miRNAs differed significantly among the four groups. Heat mapping demonstrated that the miRNA profiles from hepatic failure and portal hypertension type were clustered differently from those of the gradually progressive type and controls. Furthermore, we focused on miR-139-5p, which has an adequate number of total short reads. Quantitative reverse transcription PCR showed that miR-139-5p was significantly downregulated in clinically advanced PBC. Also, examination of liver tissues demonstrated that the expression of lymphocyte-derived miR-139-5p was significantly higher in hepatocytes. In vitro, the level of TNF-alpha was significantly elevated in supernatant of cells with upregulation of miR-139-5p. Furthermore, c-FOS gene transcription was repressed. Thus, we have demonstrated a novel inflammation-regulatory mechanism involving TNF-alpha and c-FOS transcription through miR-139-5p in the NF-kappaB signaling pathway. We conclude that the specific miRNA miR-139-5p might be involved in the pathogenesis of PBC, especially during clinical progression. PMID- 27668892 TI - Belief in the immutability of attitudes both increases and decreases advocacy. AB - People with an entity theory of attitudes (i.e., the belief that attitudes are relatively unchanging) are more certain of their attitudes than are people with an incremental theory (i.e., the belief that attitudes are relatively malleable), and people with greater attitude certainty are generally more willing to try to persuade others. Combined, these findings suggest that an entity theory should foster greater advocacy. Yet, people with entity theories may be less willing to advocate because they also perceive others' attitudes as unchanging. Across 5 studies, we show that both of these countervailing effects occur simultaneously and cancel each other out. However, by manipulating how advocacy is framed (as standing up for one's views or exchanging one's views with others), whom people focus on (themselves or others), or which implicit theory applies to oneself versus others, each implicit theory can either increase or decrease willingness to advocate. (PsycINFO Database Record PMID- 27668893 TI - Who wants to get to the top? Class and lay theories about power. AB - We investigated class-based differences in the propensity to seek positions of power. We first proposed that people's lay theories suggest that acquiring power requires playing politics-manipulating one's way through the social world, relying on a pragmatic and Machiavellian approach to impression management and social relationships to get ahead. Then, drawing on empirical work portraying individuals with relatively low social class as more strongly focused on others and less focused on themselves, we hypothesized that these individuals would show less interest in seeking positions of power than their high-class counterparts, because they feel less comfortable engaging in political behavior. We tested these ideas in 7 studies. Our findings indicated that, even though individuals with relatively low social class see political behavior as necessary and effective for acquiring positions of power, they are reluctant to do it; as a result, they have a weaker tendency to seek positions of power compared to individuals with relatively high social class. Consistent with our theorizing, we also found that individuals with relatively low social class intend to seek positions of power as much as their high-class counterparts when they can acquire it through prosocial means (Study 2), and when they reconstrue power as serving a superordinate goal of helping others (Study 4). Moreover, we checked the robustness of our findings by measuring social class in a number of ways within each study, and examined whether our results held across each measure. Together, our findings suggest that the common belief that political behavior is required for advancement may help explain why class inequalities persist and why creating class-based diversity in upper-level positions poses a serious challenge. (PsycINFO Database Record PMID- 27668890 TI - Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin alphaV. AB - Tenascin-C is expressed in choroidal neovascular (CNV) membranes in eyes with age related macular degeneration (AMD). However, its role in the pathogenesis of CNV remains to be elucidated. Here we investigated the role of tenascin-C in CNV formation. In immunofluorescence analyses, tenascin-C co-stained with alpha-SMA, pan-cytokeratin, CD31, CD34, and integrin alphaV in the CNV membranes of patients with AMD and a mouse model of laser-induced CNV. A marked increase in the expression of tenascin-C mRNA and protein was observed 3 days after laser photocoagulation in the mouse CNV model. Tenascin-C was also shown to promote proliferation and inhibit adhesion of human retinal pigment epithelial (hRPE) cells in vitro. Moreover, tenascin-C promoted proliferation, adhesion, migration, and tube formation in human microvascular endothelial cells (HMVECs); these functions were, however, blocked by cilengitide, an integrin alphaV inhibitor. Exposure to TGF-beta2 increased tenascin-C expression in hRPE cells. Conditioned media harvested from TGF-beta2-treated hRPE cell cultures enhanced HMVEC proliferation and tube formation, which were inhibited by pretreatment with tenascin-C siRNA. The CNV volume was significantly reduced in tenascin-C knockout mice and tenascin-C siRNA-injected mice. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of CNV via integrin alphaV in a paracrine manner. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of CNV development associated with AMD. PMID- 27668894 TI - American individualism rises and falls with the economy: Cross-temporal evidence that individualism declines when the economy falters. AB - Past work has shown that economic growth often engenders greater individualism. Yet much of this work charts changes in wealth and individualism over long periods of time, making it unclear whether rising individualism is primarily driven by wealth or by the social and generational changes that often accompany large-scale economic transformations. This article explores whether individualism is sensitive to more transient macroeconomic fluctuations, even in the absence of transformative social changes or generational turnover. Six studies found that individualism swelled during prosperous times and fell during recessionary times. In good economic times, Americans were more likely to give newborns uncommon names (Study 1), champion autonomy in children (Study 2), aspire to look different from others (Study 3), and favor music with self-focused language (Study 4). Conversely, when the economy was floundering, Americans were more likely to socialize children to attend to the needs of others (Study 2) and favor music with other-oriented language (Study 4). Subsequent studies found that recessions engendered uncertainty (Study 5) which in turn tempered individualism and fostered interdependence (Study 6). (PsycINFO Database Record PMID- 27668895 TI - Preparing for Better Health and Health Care for an Aging Population. PMID- 27668896 TI - Latent tuberculosis infection (LTBI): a real host defence or a permanent threat? AB - Screening of latent infection by Mycobacterium tuberculosis (LTBI) and treatment of positive subjects is the key point in the prevention of TB; such a strategy should be performed mainly among individuals with risk of progression. Progression from LTBI to active TB is highest both in recent contacts of patients with active TB, and in immunocompromised subjects. Therefore, LTBI could either be considered a permanent host defence or, seen from the opposite point of view, it could represent a long-lasting threat if the efficiency of the immune system declines over a lifetime. Interferon gamma release assays (IGRAs) show better sensitivity and specificity than the Mantoux test. PMID- 27668897 TI - Innovations in the field of fungal biofilms: looking for new targets and new chemical compounds. AB - Biofilms pose a serious problem for public health. Penetration of pharmacological agents within a biofilm is hampered by the morphological structure of such microbial communities. A biofilm infection therefore entails adverse outcomes both in the field of cost management and patient prognosis. The problem is further complicated if the drugs available to combat a biofilm-related fungal infection versus a bacterial one are compared: in the case of a fungal infection, the drugs available are less efficacious than antibiotics used to counteract a bacterial infection. Furthermore, even the fairly recent introduction of antifungals, such as echinocandins, start presenting some limits of usage, such as ineffectiveness in treating some fungal populations and increased resistance. It therefore becomes imperative to search for innovative molecules in order to combat this condition. The discovery of new molecules and/or new targets can make a difference. This paper illustrates the main innovative molecules that are coming to light in the field of infection by fungal biofilms. PMID- 27668898 TI - Antimicrobial susceptibility against penicillin, ampicillin and vancomycin of viridans group Streptococcus in oral microbiota of patients at risk of infective endocarditis. AB - The viridans group Streptococci (VGS) are most abundant in the mouth; in some instances they might emerge as pathogens particularly in infective endocarditis (IE). In this study, we aimed to define and determine the susceptibility against antibiotics of VGS that are members of the oral microbiota of patients exhibiting a risk of developing IE. Forty-nine patients at risk of infective endocarditis were included in the study. Identification of the bacteria was performed using API STREP (bioMerieux, France). Gradient test strips (E-Test, France) were used to determine MIC of the bacteria against penicillin, ampicillin, and vancomycin. The distribution of the isolated VGS groups was determined as follows: Streptococcus mitis 32.6% and anginosus group - 32.6%, S. sanguinis group - 16.3%, S. mutans group - 12.2%, and S. salivarius group - 6.1%. The rates of resistance and reduced sensitivity of the isolates for penicillin and ampicillin were determined at 61.2% and 55.1%, respectively. However, all isolates were found to be susceptible to vancomycin. We conclude that the antimicrobial resistance of VGS should be determined on a regular basis locally, and decisions on therapeutic and prophylactic interventions should be given taking this resistance into consideration. PMID- 27668899 TI - Report of data on children with non-typhi Salmonella gastroenteritis in a three year period. AB - The purpose of this study was to evaluate the clinical and laboratory data of children with acute gastroenteritis caused by non-typhoid Salmonella spp. infections. Clinical (demographic data, symptoms and findings) and laboratory data (stool microscopy, rapid antigen tests, culture, multiplex polymerase chain reaction and blood test results) of children with acute gastroenteritis caused by non-typhoid Salmonella spp. between January 2010 and October 2012 were evaluated. Differences between the groups for categorical variables were estimated with a chi-square or Fisher exact test; for continuous variables with two independent samples a t test was used. P values < 0.05 were considered statistically significant. Sixty-seven children, 39 (58.2%) males and 28 (41.8%) females aged between 1 - 16 years (mean +/- SD: 4.64 +/- 2.91), were diagnosed with acute bacterial gastroenteritis caused by non-typhoid Salmonella spp. The main serotypes are Salmonella enteritidis (85%) and Salmonella typhimurium (7.5%). The presenting symptoms were diarrhoea (95.5%), fever (61.1%), vomiting (34.3%), abdominal pain (32.8%), loss of appetite (7.4%) and malaise (7.4%). Fever and dehydration (moderate and/or severe) were detected in 11 (16.4%) patients. The mean leukocyte count was 10.930/MUL [95% confidence interval (CI), SD: +/- 5.710/MUL], neutrophil count was 7.880/MUL (95% CI, SD: +/- 4.960/MUL), CRP was 64.16 mg/L (95% CI, SD: +/- 76.24 mg/L), and erythrocyte sedimentation rate was 34.72 mm/hour (95% CI, SD: +/- 13.64 mm/h). Stool microscopy was positive for leukocytes in 18 patients (26.8%). The definitive diagnosis was made with positive stool culture (n = 65) and/or PCR test (n = 4). Viral antigen positivity was detected in 10 patients (14.9%), evaluated as viral co-infection and false positive results. Antibiotic therapy and hospitalization were required in 26 (38.8%) and 23 (34.3%) patients, respectively. Salmonella carriage was detected in one patient (1.5%). Bloody diarrhoea, leukocytes in stool with an increased erythrocyte sedimentation rate and a CRP level without overt leukocytosis may indicate Salmonella infection. Viral antigens may cause false positive results in fast antigen tests in cases where clinical and laboratory findings indicate bacterial aetiology. Stool culture is a reference method in diagnosis whereas some agents may be detected via molecular techniques (polymerase chain reaction) in spite of negative culture. Multiplex polymerase chain reaction may be used to detect Salmonella spp. and may reveal false positivity for viruses as well as the detection of other bacteria. PMID- 27668901 TI - Hepatitis C and immigration: a multicentre study. AB - This retrospective multicentre study aims to evaluate the clinical and epidemiological features of HCV infection in a cohort of immigrants in Italy. Tests were carried out on 194 HCV positive subjects, who represented 5.7% of the participants at baseline screening: the virological (viral load, genotype) and biochemical appearance of their infection was determined, and the disease was staged by histological examination in the patients who had indicated their willingness. Standard therapy (peg-interferon + ribavirin) was implemented in patients who agreed to undergo treatment. The majority of immigrants were of East European origin (48.4%), females were globally slightly predominant and the average age was 41.4 years. Of the 194 patients, 119 (63.1%) proved to be viraemic: genotype 1 was the most frequent, followed by genotype 4, the latter mainly in African patients. The histological staging of liver disease conducted in 25 patients showed mild hepatitis in 13 subjects, moderate/severe hepatitis in eight subjects and cirrhosis in four. Although 45 out of 119 patients (37.8%) with determinable HCV RNA agreed to undergo treatment, 11 of them independently stopped taking medication before the course of therapy was completed, without any significant side effects. At the sixth month of follow-up, the overall sustained virological response (SVR) was shown by 22/45 patients (48.8%). In our study, migrant populations had higher rates of HCV-related chronic hepatitis than the indigenous population; in some cases the infections were contracted in the country of origin, but in others the infection took place in Italy. The most commonly represented genotype, besides 1, was 4, especially among Africans. The therapeutic management of immigrants proved to be very difficult, mostly but not exclusively because of social factors. PMID- 27668900 TI - Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission. AB - Predicting methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) avoids inappropriate antimicrobial empirical treatment and enhances infection control. We describe risk factors for colonisation/infection related to MRSA (MRSA-C/I) in critically ill patients once in the ICU and on ICU admission, and search for an easy-to-use predictive model for MRSA colonisation/infection on ICU admission. This multicentre cohort study included 69,894 patients admitted consecutively (stay>24h) in April-June in the five-year period 2006-2010 from 147 Spanish ICUs participating in the National Surveillance Study of Nosocomial Infections in ICUs (ENVIN-HELICS). Data from all patients included were used to identify risk factors for MRSA-C/I during ICU stays, from admission to discharge, using uni- and multivariable analysis (Poisson regression) to check that the sample to be used to develop the predictive models was representative of standard critical care population. To identify risk factors for MRSA-C/I on ICU admission and to develop prediction models, multivariable logistic regression analysis were then performed only on those admitted in 2010 (n=16950, 2/3 for analysis and 1/3 for subsequent validation). We found that, in the period 2006-2010, 1046 patients were MRSA-C/I. Independent risk factors for MRSA-C/I in ICU were: age>65, trauma or medical patient, high APACHE-II score, admitted from a long-term care facility, urinary catheter, previous antibiotic treatment and skin-soft tissue or post-surgical superficial skin infections. Colonisation with several different MDRs significantly increased the risk of MRSA-C/I. Risk factors on ICU admission were: male gender, trauma critical patient, urgent surgery, admitted from other ICUs, hospital ward or long-term facility, immunosuppression and skin-soft tissue infection. Although the best model to identify carriers of MRSA had a good discrimination (AUC-ROC, 0.77; 95% CI, 0.72-0.82), sensitivity was 67% and specificity 76.5%. Including more complex variables did not improve prediction capability. Our conclusion is that clinical-demographic risk factors for colonisation/infection related to MRSA should not be used to accurately identify patients who would benefit from empirical anti-MRSA treatment or from specific preventive measures. Independent risk factors for MRSA colonisation/infection during ICU stay and on ICU admission are described. The latter should be considered in future studies for MRSA prediction. PMID- 27668902 TI - Streptococcus agalactiae: prevalence of antimicrobial resistance in vaginal and rectal swabs in Italian pregnant women. AB - Intrapartum antibiotic prophylaxis (IAP) reduces both the vertical transmission of Streptococcus agalactiae or Group B Streptococcus (GBS) and the early onset of neonatal sepsis. However, existing guidelines do not recommend that antimicrobial susceptibility testing (AST) be routinely performed. Penicillin or ampicillin are indicated as first-choice antibiotics, cefazolin being an alternative in the case of history of mild allergic reactions, and vancomycin or clindamycin an alternative in the event of severe reactions. We performed a cross-sectional analysis to identify the presence of any bacterial resistance towards the antibiotics most frequently used for IAP in pregnant women with GBS positive vaginal-rectal swabs, in the Pistoia area of central Italy. Of the 255 tested samples, 65 (25.5%) were positive for GBS. Sensitivity to glycopeptides was over 90%, but lower to ampicillin and penicillin (87.10% and 87.93% respectively). Resistance towards clindamycin and erythromycin was as high as 43.75% and 32.20%. All tested GBS proved susceptible to moxifloxacin, linezolid and tigecycline. Our observed prevalence is aligned or slightly higher than data reported in other series. The less than full effectiveness and low percentages of ampicillin and penicillin sensitivity observed give cause for concern. We confirmed the increase in clindamycin and erythromycin resistance. Glycopeptides can be used as second line antibiotics, but the complete AST of GBS should always be performed before IAP. Given that gentamicin is used synergically with penicillin when treating chorioamnionitis, it needs to be always included in the AST. This is the first study on the GBS sensitivity profile in Tuscany. Further investigation on a larger scale is required prior to implementing any changes in the current guidelines. PMID- 27668903 TI - Identification of aminoglycoside resistance genes by Triplex PCR in Enterococcus spp. isolated from ICUs. AB - Early detection of antibiotic-resistant enterococci is an important part of patient treatment. Therefore, the aim of the present study was to evaluate the resistance patterns and simultaneously identify and characterise the resistance genes in Enterococcus spp. using a triplex polymerase chain reaction (PCR) method. In all, 150 consecutive Enterococcus spp were collected from several hospitals in Tehran (Iran) from January to December 2015. The Enterococcus species were identified by standard phenotypic/biochemical tests and PCR. The antimicrobial resistance patterns were determined using a disk diffusion method. The triplex PCR method was designed to identify gentamicin and other aminoglycoside resistance genes. Among the 150 Enterococcus specimens, 87 cases (58%) were Enterococcus faecalis, and 63 cases (42%) were Enterococcus faecium. The highest frequency of resistance was observed for tetracycline while the lowest was found for vancomycin. Among the identified samples, 56.9% contained the aac(6')-Ie-aph(2'')-Ia gene, 22.2% contained the aph(3')-IIIa gene, and 38.8% contained the ant(4')-?a gene. Eight percent of the isolates contained the three aminoglycoside resistance genes. Data analysis showed that there was a significant correlation between the phenotypic gentamicin resistance and the presence of the aminoglycoside resistance genes (18.9%, p <0.05), while the correlation between the phenotypic streptomycin resistance and the corresponding genes was not significant (2.8%, p >=0.5). Nearly half of the identified Enterococcus strains had increased aminoglycoside resistance. The direct correlation between resistance genes, such as the aminoglycoside resistance factor, and phenotypic resistance was not significant (p > 0.05). PMID- 27668904 TI - A family cluster of hepatitis A virus due to an uncommon IA strain circulating in Campania (southern Italy), not associated with raw shellfish or berries: a wake up call to implement vaccination against hepatitis A? AB - Hepatitis A virus is a widely occurring disease, with different prevalence rates between countries in the North and West and those in the South and East. In Italy endemicity is low/medium, but not homogeneously distributed: in the northern/central regions a large hepatitis A outbreak due to genotype IA, related to the consumption of contaminated mixed frozen berries, occurred between 2013 and 2014, whereas in southern Italian regions recurrent outbreaks of hepatitis A, due to the IB genotype, still result from consumption of raw seafood. In 2014 an uncommon genotype IA strain was isolated from five patients (2 adults and 3 children) with hepatitis A, living in the surroundings of Naples (Campania) who did not have any of the most common risk factors for hepatitis A in Italy, such as consumption of raw shellfish or frozen berries, or travel to endemic countries. Moreover, based on the analysis of viral sequences obtained, this strain differed from several others in the national database, which had been recently isolated during Italian outbreaks. This case report reinforces the need to implement both information campaigns about the prevention of hepatitis A and vaccination programmes in childhood; in addition, it would be suitable to sequence strains routinely not only during large outbreaks of hepatitis A in order to obtain a more detailed national database of HAV strains circulating in Italy. PMID- 27668906 TI - Postnatal cytomegalovirus infection in an infant with congenital thrombocytopenia: how it can support or mislead the diagnosis of Wiskott-Aldrich syndrome. AB - A male newborn developed a post-natal cytomegalovirus (CMV) infection, arising in the clinical setting of congenital thrombocytopenia, which was diagnosed as being alloimmune. The evidence of active CMV infection in an infant showing slow resolution lower airways infection, persistent neonatal and low platelet volume thrombocytopenia, and diffuse eczema (associated to very high levels of serum immunoglobulin E) led to the diagnosis of Wiskott-Aldrich syndrome (WAS) before the third month of life, despite the presence of several confounding clinical factors. The correct interpretation of all clinical features supported the precocious diagnosis of WAS. PMID- 27668905 TI - Atypical clinical presentation of meningococcal meningitis: a case report. AB - A young woman was examined in the Emergency Department for fever, pharyngitis and widespread petechial rash. Physical examination, including neurological evaluation, did not show any other abnormalities. Chest X-ray was negative. Blood exams showed leukocytosis and CPR 20 mg/dL (nv<0.5 mg/dL). On the basis of these results and petechial rash evidence, lumbar puncture was performed. CSF was opalescent; physico-chemical examination showed: total proteins 2.8 (nv 0.15 0.45), glucose 5 (nv 59-80), WBC 7600/MUL (nv 0-4/ MUL). In the hypothesis of meningococcal meningitis, antimicrobial therapy was started. Blood and cerebrospinal fluid cultures were positive for N. meningitidis. During the first hours the patient experienced hallucinations and mild psychomotor agitation, making a spontaneous recovery. A brain MRI showed minimal extra-axial inflammatory exudates. She was discharged after 10 days in good condition. We underline the need to consider meningococcal meningitis diagnosis when any suggestive symptom or sign is present, even in the absence of the classic meningitis triad, to obtain earlier diagnosis and an improved prognosis. PMID- 27668907 TI - Recurrent complicated urinary tract infection due to rare pathogen Sphingomonas paucimobilis: contamination or real deal? AB - Sphingomonas paucimobilis is an aerobic, oxidase-positive, yellow-pigmented, non fermentative, Gram-negative opportunistic pathogen that rarely causes infections in humans. It is commonly found in nosocomial environments and, despite its low clinical virulence, it can be responsible for several different infections especially among patients with underlying disease. Here we describe a clinical case of a 46-year-old male paraplegic patient with a history of neurogenic bladder due to insulin-dependent diabetes mellitus and renal failure who was admitted to the urology clinic of a university hospital in Kirsehir, Turkey, with the complaints of urinary tract infection (UTI) including fever, chills, dysuria, abdominal and back pain. The urine culture was positive for Sphingomonas paucimobilis identified by the Vitek-2 system and the patient was successfully treated with oral co-trimoxazole 800/160 mg twice a day for ten days associated to cefixime and fosfomycin. A literature review of UTIs associated to Sphingomonas paucimobilis is reported as well. PMID- 27668909 TI - Zika virus infection: Challenge. AB - Not available. PMID- 27668908 TI - HIV positive patient with HSV-2 encephalitis: case report. AB - Incidence of brain infections in Human Immunodeficiency Virus (HIV) positive patients is reduced after the availability of current high active antiretroviral therapy (HAART). Herpes Simplex Virus type 2 (HSV-2) is an infrequent cause of encephalitis in HIV patients despite it is frequently involved in sexual transmitted infections. Here, we report a case of HSV-2 encephalitis occurring in a patient without full suppression of HIV replication within the brain. A 38 year old HIV infected man was admitted to our department because of recurrent generalized seizure and fever during the previous 24 hours. Eight months before our observation the patient was switched from a protease inhibitor based regimen to a rilpivirine-based regimen without any evidence of HIV-RNA replication in the plasma. When the patient was admitted in our hospital, he was febrile and moderately confused, no deficit of cranial nerves was reported, motility was conserved, but he was unable to walk. Laboratory examinations performed at admission demonstrated an increase of cerebrospinal fluid (CSF) protein and cells with lymphocyte prevalence, and normal CSF glucose. HSV-2-DNA and HIV-RNA were present within CSF at admission. Nuclear Magnetic Resonance imaging of the brain revealed lesions of the medial part of both temporal lobes including hippocampus without any sign of bleeding. A 21-day course of acyclovir therapy was administered with consistent improvement of clinical findings and disappearance of HSV-2-DNA within CSF. After the episode, HAART was switched to a regimen with high CSF penetrability containing abacavir, lamivudine, darunavir and ritonavir. Twelve months after HSV-2 encephalitis neurologic evaluation was normal, but symptoms of depression were reported, HIV-RNA remained undetectable both in the plasma and CSF, and CD4+ lymphocytes were above 500/MUL. No opportunistic infection was reported. Patients switched to regimen well tolerated such those containing rilpivirine, that have poor drug concentration within CSF could be considered at risk for opportunistic infection of the brain. Further larger investigation needs to confirm this finding. PMID- 27668910 TI - Daniel Molliere (1848-1890), the French anatomist and surgeon, and his encounters with nosocomial infections in the operating theatre. AB - Daniel Molliere, was a French anatomist and surgeon, born in Lyon, who succeeded in his short life in making his mark in surgery. He was a prolific writer who left a series of medical treatises and a committed surgeon who was responsible for various significant innovative apparatuses in the medical sper. As he lived in an era when the role of microbe had already been recognized, he was among the first to use antisepsis and install extreme measures against microbes, both in the air and on the skin'. Fountains with fresh clean water, carbonic acid, cross ventilation, medical blouses, combined with Valette's apparatus for the dressing of amputations, were some of his precautions to reduce surgical infections and post-operative mortality. PMID- 27668911 TI - National Institute of Environmental Health Sciences: 50 Years of Advancing Science and Improving Lung Health. AB - The American Thoracic Society celebrates the 50th anniversary of the National Institute of Environmental Health Sciences (NIEHS). The NIEHS has had enormous impact through its focus on research, training, and translational science on lung health. It has been an advocate for clean air both in the United States and across the world. The cutting-edge science funded by the NIEHS has led to major discoveries that have broadened our understanding of the pathogenesis and treatment for lung disease. Importantly, the NIEHS has developed and fostered mechanisms that require cross-cutting science across the spectrum of areas of inquiry, bringing together environmental and social scientists with clinicians to bring their expertise on specific areas of investigation. The intramural program of the NIEHS nurtures cutting-edge science, and the extramural program encourages investigator-initiated research while at the same time providing broader direction through important initiatives. Under the umbrella of the NIEHS and guided by Dr. Linda Birnbaum, the director of the NIEHS, important collaborative programs, such as the Superfund Program and the National Toxicology Program, work to discover mechanisms to protect from environmental toxins. The American Thoracic Society has overlapping goals with the NIEHS, and the strategic plans of both august bodies converge to synergize on population lung health. These bonds must be tightened and highlighted as we work toward our common goals. PMID- 27668912 TI - Unilateral Lung Whiteout in Children: Four Cases and a Discussion of Management. AB - Unilateral lung whiteout is not a common pediatric chest radiograph finding, but when it is encountered, timely and accurate interpretations of the radiograph are required because life-threatening respiratory failure can be associated. Lung whiteout may result from several conditions, and the differential diagnosis has a broad range. We describe 4 pediatric patients with different etiologies of unilateral lung whiteout: a large pleural effusion, mainstem bronchial plugging with a large cast, a mediastinal tumor, and consolidation. The ultimate causal diagnosis may not be initially obvious, but valuable clues can usually be found in the conventional chest radiograph to assist with appropriate early management. Chest ultrasound provides additional information, and we recommend it as the second examination for such patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. PMID- 27668913 TI - Interventricular Septal Pseudoaneurysm After Blunt Chest Trauma in a 6 Year Old: An Illustrative Case and Review. AB - Motor vehicle accident is the most common cause of blunt cardiac injury (BCI) in children (85.3%) due to the height of the child in relation to proper restraints and the compliant pediatric rib cage (J Trauma. 1996;40:200-202). Trauma to the chest wall may lead to injury of the myocardium, resulting in myocardial contusion, ventricular septal defect (VSD), ventricular free wall rupture, or valve compromise (J Trauma. 1996;40; 200-202; Heart Lung. 2012;41:200-202; J Inj Violence Res. 2012;4:98-100). There are several proposed mechanisms for the formation of VSD after blunt chest trauma including rupture of ischemic myocardium related to the initial trauma and reopening of a spontaneously closed congenital VSD. Also, chest trauma during isovolumetric contraction of the ventricles may generate enough intraventricular force to cause myocardial rupture (J Trauma. 1996;40:200-202; J Inj Violence Res. 2012;4:98-100; Korean J Pediatr. 2011;54:86-89; Ann Thorac Surg. 2012;94:1714-1716; J Emerg Trauma Shock. 2012;5:184-187). Previous case reports highlight the formation of a true VSD after BCI and the requirement of emergent repair (J Emerg Trauma Shock. 2012;5:184-187; Am Heart J. 1996;131:1039-1041; Korean Circ J. 2011;41:625-628; Ann Thorac Surg 2013;96:297-298; Kardiol Pol. 2013;71:992; Chin Med J. 2013;126:1592-1593). Reported is a case of a 6-year-old girl who developed an interventricular septal pseudoaneurysm after a motor vehicle accident of pedestrian versus car. On the day of presentation, she developed bradycardia after emergent surgical repair for abdominal trauma that required cardiopulmonary resuscitation including 5 minutes of chest compressions. At the time of resuscitation, an emergent transthoracic echocardiogram noted an interventricular pseudoaneurysm. She has been followed with serial transthoracic echocardiograms and has not required surgical intervention. We discuss the risk factors, prevalence, and diagnostic studies and recommended treatment options for structural heart disease after BCI. PMID- 27668914 TI - Evaluation and Management of Acute-Onset Hemiparesis in an Adolescent With Leukemia. AB - Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis. He was initially suspected as having a possible ischemic stroke. Magnetic resonance imaging (diffusion-weighted and fluid-attenuated inversion recovery sequence) demonstrated focal areas of diffusion restriction, an early sign of delayed-onset methotrexate neurotoxicity. Our patient received appropriate supportive care and leucovorin rescue with gradual clinical recovery, after a prolonged hospitalization and acute care rehabilitation over the course of several months. Our case illustrates the need for ED providers to consider methotrexate neurotoxicity in pediatric oncology patients presenting with acute neurologic changes. PMID- 27668915 TI - The Impact of Mental Health Services in a Pediatric Emergency Department: The Implications of Having Trained Psychiatric Professionals. AB - OBJECTIVES: This study assessed improvement in the emergency department (ED) length of stay and costs after implementation of an ED program which added board certified psychiatrists and trained psychiatric social workers to the pediatric ED. METHODS: A retrospective medical record and administrative data review were conducted for all pediatric psychiatric visits of children aged 5 to 18 years who were seen and discharged from the Greenville Memorial Hospital ED between January 1, 2007, and June 31, 2013. These subjects were diagnosed by the ED physician at the time of the visit using codes ranging from 290.0 to 319.0 based on the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. RESULTS: The mean (SD) age of children in the postprogram period (14.3 +/- 3.1) was younger than during the preprogram period (14.9 +/- 3.1) (P < 0.001) with the greatest increase in the 11- to 15-year age group (42% vs 35%, respectively). Patients in the postprogram period were significantly more likely to be discharged to a psychiatric hospital than during the pre-program period (18% vs 9%, respectively). After the initiation of the program, ED length of stay decreased significantly from 14.7 to 12.1 hours (P < 0.001) and costs per visit decreased slightly from US $602 to US $588 (this difference was not statistically significant). CONCLUSIONS: Although this model of care has significant costs associated with it, the efficiency of care for psychiatric pediatric patients in the ED improved after targeted training of ED staff and provision of these specialized services within the ED. PMID- 27668916 TI - Carotid Artery Dissection With Associated Territory Stroke After a Minor Head Trauma in a Healthy 4-Month-Old Child. AB - Internal carotid artery (ICA) dissections with associated stroke are rare events in infants. The usual pathomechanisms include direct trauma to the artery, blunt intraoral trauma, or child abuse. We describe the case of a 4-month-old male patient with ICA dissection and associated middle cerebral artery territory infarction associated with hyperextension/hyperrotation after a minor head injury. Upon treatment with anticoagulants, the patient showed significant improvement of the left-sided hemiparesis. Hemorrhagic transformation that presented shortly after middle cerebral artery infarction did not further increase under heparin treatment and prevented further embolism. In conclusion, hyperextension and/or hyperrotation in minor head trauma is a possible pathomechanism for ICA dissection in infants. However, the scenario is extremely rare, and to our best knowledge, this is the first report describing it. In our patient, anticoagulation did not worsen hemorrhagic transformation. PMID- 27668917 TI - Predictive Factors for Clinical Severity and Cardiopulmonary Arrest in Pediatric Electrical Injuries in Southeastern Turkey. AB - OBJECTIVE: An electrical injury (EI) is an emergency that causes high morbidity and mortality each year. The aim of this study was to define the epidemiological, clinical, and laboratory factors that might predict severe patients and cardiac arrest in pediatric EI cases. METHODS: All of the patients' medical files were reviewed retrospectively through a 2-year period for the demographic, clinical, and laboratory findings. The patients were classified into the severe injury group or the mild injury group. The SPSS (Chicago, Ill) software was used to analyze the data. RESULTS: Among the 38 patients, 18 patients (47.4%) were in the mild group, and 20 patients (52.6%) were in the severe group. Low-voltage injuries were observed in 35 (92.1%) of the patients. Most of the severe patients were injured with low voltage (75%) and in household settings (85%). Plug and sockets were the most observed source of the injuries in all of the patients, whereas water-related injuries were most prevalent in the severe group. The source of injury was different in the mild and severe groups (P = 0.009). In the severe group, 13 patients (34.2%) were resuscitated after cardiopulmonary arrest. In the multivariate analysis of the demographic data, the most predictive parameters for cardiac arrest and the clinical severity in EIs are the factors of electrical cables and water. CONCLUSIONS: Electrical injuries are a significant concern in the pediatric population. Our results showed that low voltage and household electricity could cause morbidity and mortality. PMID- 27668918 TI - Profile of Interfacility Emergency Department Transfers: Transferring Medical Providers and Reasons for Transfer. AB - OBJECTIVES: The aim of this study was to determine the reasons for pediatric emergency department (ED) transfers and the professional characteristics of transferring providers. METHODS: We performed a multicenter, cross-sectional survey of ED medical providers transferring patients younger than 18 years to 1 of 4 tertiary care children's hospitals. Referring providers completed surveys detailing the primary reasons for transfer and their medical training. RESULTS: The survey data were collected for 25 months, during which 641 medical providers completed 890 surveys, with an overall response rate of 25%. Most pediatric patients were seen by physicians (89.4%) with predominantly general emergency medicine training (64.2%). The median age of patients seen was 5.6 years. The 3 most common diagnoses were closed extremity fracture (12.2%), appendicitis (11.6%), and pneumonia (3.7%). The 3 most common reasons for transfer were need for medical/surgical subspecialist consultation (62.6%), admission to the inpatient unit (17.1%), and admission to the intensive care unit (6.5%). When asked about the need for supportive pediatric services, referring providers ranked pediatric subspecialty and pediatric inpatient unit availability as the highest. CONCLUSIONS: Most pediatric interfacility ED transfers are referred by general emergency medicine physicians who often transfer for inpatient admission or subspecialty consultation. Understanding the needs of the community-based ED providers is an important step to forming more collaborative efforts for regionalized pediatric emergency care. PMID- 27668919 TI - The Utility of Bedside Lung Ultrasound Findings in Bronchiolitis. AB - OBJECTIVES: Recent literature suggests that bedside lung ultrasound may have a role in the evaluation of infants with bronchiolitis. B lines, which are multiple and diffuse vertical artifacts spreading from the lung pleural interface to the edge of the ultrasound screen, have been associated with thickened interlobular septa, extravascular lung water, and diffuse parenchymal disease. The aims of this study were (1) to describe the prevalence of B lines in children younger than 24 months presenting to the emergency department with wheezing, (2) to determine the interrater reliability of lung ultrasound findings in this setting, and (3) to determine the association of B lines with atopy and other clinical findings. METHODS: This was a pilot, prospective, observational study of a convenience sample of patients younger than 2 years presenting with wheezing to a large academic pediatric hospital emergency department. Investigators performed lung ultrasound examinations, and a second provider reviewed the ultrasound examinations to determine interrater reliability. We performed univariate analyses to test for associations between ultrasound findings and atopy, acute illness severity, age, and treatment response. RESULTS: Studies were obtained on 29 patients (mean [SD] age, 291 [187] days; 62% male). Twenty-one patients (72%) had compact B lines. B lines were significantly associated with older age and an absence of atopic features. There was poor correlation of lung ultrasound examination interpretation among enrolling providers. CONCLUSIONS: In this small sample of patients with bronchiolitis, B lines were associated with older age and an absence of atopic features. Lung ultrasound interpretation had poor interrater reliability. PMID- 27668920 TI - Two-Thumb Encircling Technique Over the Head of Patients in the Setting of Lone Rescuer Infant CPR Occurred During Ambulance Transfer: A Crossover Simulation Study. AB - OBJECTIVE: The purpose of this study was to determine if the over-the-head 2 thumb encircling technique (OTTT) provides better overall quality of cardiopulmonary resuscitation compared with conventional 2-finger technique (TFT) for a lone rescuer in the setting of infant cardiac arrest in ambulance. METHODS: Fifty medical emergency service students were voluntarily recruited to perform lone rescuer infant cardiopulmonary resuscitation for 2 minutes on a manikin simulating a 3-month-old baby in an ambulance. Participants who performed OTTT sat over the head of manikins to compress the chest using a 2-thumb encircling technique and provide bag-valve mask ventilations, whereas those who performed TFT sat at the side of the manikins to compress using 2-fingers and provide pocket-mask ventilations. RESULTS: Mean hands-off time was not significantly different between OTTT and TFT (7.6 +/- 1.1 seconds vs 7.9 +/- 1.3 seconds, P = 0.885). Over-the-head 2-thumb encircling technique resulted in greater depth of compression (42.6 +/- 1.4 mm vs 41.0 +/- 1.4 mm, P < 0.001) and faster rate of compressions (114.4 +/- 8.0 per minute vs 112.2 +/- 8.2 per minute, P = 0.019) than TFT. Over-the-head 2-thumb encircling technique resulted in a smaller fatigue score than TFT (1.7 +/- 1.5 vs 2.5 +/- 1.6, P < 0.001). In addition, subjects reported that compression, ventilation, and changing compression to ventilation were easier in OTTT than in TFT. CONCLUSIONS: The use of OTTT may be a suitable alternative to TFT in the setting of cardiac arrest of infants during ambulance transfer. PMID- 27668921 TI - Script Concordance Testing to Determine Infant Lumbar Puncture Practice Variation. AB - OBJECTIVES: Script concordance testing (SCT) is used to assess clinical decision making. We explore the use of SCT to (1) quantify practice variations in infant lumbar puncture (LP) and (2) analyze physician's characteristics affecting LP decision making. METHODS: Using standard SCT processes, a panel of pediatric subspecialty physicians constructed 15 infant LP case vignettes, each with 2 to 4 SCT questions (a total of 47). The vignettes were distributed to pediatric attending physicians and fellows at 10 hospitals within the INSPIRE Network. We determined both raw scores (tendency to perform LP) and SCT scores (agreement with the reference panel) as well as the variation with participant factors. RESULTS: Two hundred twenty-six respondents completed all 47 SCT questions. Pediatric emergency medicine physicians tended to select LP more frequently than did general pediatricians, with pediatric emergency medicine physicians showing significantly higher raw scores (20.2 +/- 10.2) than general pediatricians (13 +/ 15; 95% confidence interval for difference, 1, 13). Concordance with the reference panel varied among subspecialties and by the frequency with which practitioners perform LPs in their practices. CONCLUSION: Script concordance testing questions can be used as a tool to detect subspecialty practice variation. We are able to detect significant practice variation in the self report of use of LP for infants among different pediatric subspecialties. PMID- 27668922 TI - System Stresses in 2 Pediatric Emergency Departments and 2 Pediatric Urgent Care Centers During the 2014 Enterovirus-D68 Outbreak. AB - OBJECTIVE: To describe the association of an unprecedented large-scale Enterovirus-D68 outbreak in 2014 with changes in patient volume and acuity and system stress in 2 pediatric emergency departments and 2 pediatric urgent care centers of a single children's hospital. METHODS: We compared measures of patient volume, acuity, and system stress during the 2014 Enterovirus-D68 outbreak and the corresponding dates of the previous year. RESULTS: Both settings experienced large census increases during the Enterovirus-D68 outbreak; patient census increased significantly more in the pediatric urgent care setting (20.3%) than in the pediatric emergency departments (14.3%). Both settings had significant increases in patient acuity. The proportion of pediatric emergency department patients requiring hospital admission increased; the proportion of patients who left the pediatric urgent care setting without being seen also increased. Although there was no emergency department inpatient boarding during the 2013 comparison period, 4.4% of admitted patients required emergency department boarding during the 2014 outbreak. There was no significant change in the mean length of stay or the probability that patient admission was to the pediatric intensive care unit. CONCLUSIONS: Both the pediatric emergency departments and the pediatric urgent care centers experienced increased patient volumes and acuity and significant system stress in association with the 2014 Enterovirus-D68 outbreak. These data will inform those planning resource allocation for future large-scale viral outbreaks. PMID- 27668924 TI - Improving Health-Related Quality of Life in Wounded Warriors: The Promising Benefits of Laser Hair Removal to the Residual Limb-Prosthetic Interface. AB - BACKGROUND: Wounded warriors with lower limb amputations using prosthetics commonly develop dermatologic complaints at the residual limb-prosthetic interface, which impact their health-related quality of life (HRQOL). To optimize this interface, military dermatologists routinely treat the subset of issues related to the pilosebaceous unit with laser hair removal (LHR). OBJECTIVE: To characterize the impact of residual limb skin conditions on HRQOL in wounded warriors using lower limb prosthetics before and after treatment with LHR. METHODS AND MATERIALS: Twenty wounded warriors with lower limb amputations using prosthetics were administered a validated HRQOL survey, the Skindex-16, before and after an average of 3 treatments of LHR to their residual lower limbs. Responses were statistically analyzed within the symptoms, emotions, and functioning subscales of the survey and in aggregate. RESULTS: Statistically significant (p < .05) improvement in HRQOL was observed across the symptoms, emotions, and functioning subscales and in aggregate. CONCLUSION: Dermatologic complaints at the residual limb-prosthetic interface in patients with traumatic lower limb amputation are well-established in the literature. The authors present the first report subjectively quantifying this impact on HRQOL and the marked improvement observed with LHR to the residual limb. PMID- 27668923 TI - Catecholaminergic Polymorphic Ventricular Tachycardia as the Etiology of Emergency Medical Services-Reported Traumatic Arrest. AB - A 13-year-old girl had a witnessed loss of consciousness after a scuffle with another student at school and was found in ventricular fibrillation at the time of arrival of emergency medical services personnel. The patient was successfully defibrillated in the field and was transported to the emergency department as a presumed "traumatic arrest". The patient's initial electrocardiogram was remarkable for a prolonged QT interval, and it was discovered that multiple family members had died of cardiac events as young adults. Genetic testing subsequently revealed a mutation in the RYR2 gene, which is implicated in catecholaminergic polymorphic ventricular tachycardia. PMID- 27668925 TI - Consensus Recommendations for Combined Aesthetic Interventions Using Botulinum Toxin, Fillers, and Microfocused Ultrasound in the Neck, Decolletage, Hands, and Other Areas of the Body. AB - BACKGROUND: The popularity of aesthetic procedures in the face has led to greater disparity between treated areas and those that still show evidence of true age. Although many areas of the body often require multiple treatment procedures for optimal rejuvenation, combination therapy for specific areas is not yet well defined. OBJECTIVE: To develop recommendations for the optimal combination and ideal sequence of botulinum toxin (BoNT), hyaluronic acid, calcium hydroxylapatite (CaHA), and microfocused ultrasound with visualization in nonfacial areas across all skin phototypes. METHODS: Fifteen specialists convened under the guidance of a certified moderator. Consensus was defined as approval from 75% to 94% of all participants, whereas agreement of >=95% denoted a strong consensus. RESULTS: Recommendations have been provided for the neck, decolletage, and hands and include the timing and sequence of specific procedures when used concurrently or over several treatment sessions. Position statements are offered in lieu of consensus for the upper arms, abdomen, buttocks, and knees. CONCLUSION: Nonfacial rejuvenation often requires multiple procedures for optimal results in individuals with significant age-related changes. Further clinical studies are recommended to raise awareness of non-facial indications and provide clinicians with the best evidence for best treatment practices. PMID- 27668926 TI - Cotton plants export microRNAs to inhibit virulence gene expression in a fungal pathogen. AB - Plant pathogenic fungi represent the largest group of disease-causing agents on crop plants, and are a constant and major threat to agriculture worldwide. Recent studies have shown that engineered production of RNA interference (RNAi)-inducing dsRNA in host plants can trigger specific fungal gene silencing and confer resistance to fungal pathogens1-7. Although these findings illustrate efficient uptake of host RNAi triggers by pathogenic fungi, it is unknown whether or not such an uptake mechanism has been evolved for a natural biological function in fungus-host interactions. Here, we show that in response to infection with Verticillium dahliae (a vascular fungal pathogen responsible for devastating wilt diseases in many crops) cotton plants increase production of microRNA 166 (miR166) and miR159 and export both to the fungal hyphae for specific silencing. We found that two V. dahliae genes encoding a Ca2+-dependent cysteine protease (Clp-1) and an isotrichodermin C-15 hydroxylase (HiC-15), and targeted by miR166 and miR159, respectively, are both essential for fungal virulence. Notably, V. dahliae strains expressing either Clp-1 or HiC-15 rendered resistant to the respective miRNA exhibited drastically enhanced virulence in cotton plants. Together, our findings identify a novel defence strategy of host plants by exporting specific miRNAs to induce cross-kingdom gene silencing in pathogenic fungi and confer disease resistance. PMID- 27668927 TI - Characteristics Associated with Quality of Life in Long-Term Care Residents with Dementia: A Cross-Sectional Study. AB - BACKGROUND: To determine which characteristics are associated with quality of life (QOL) in residents with moderate to very severe dementia in long-term care facilities (LTCFs). MATERIAL AND METHODS: This was a cross-sectional analysis of a cluster randomized controlled study in 12 Dutch LTCFs that enrolled 288 residents, with moderate to severe dementia assessed with the Reisberg Global Deterioration Scale (Reisberg GDS) and QOL with the QUALIDEM. Characteristics that were hypothesized to be associated with the six domains of QOL (applicable to very severe dementia) included demographic variables, activities of daily living (Katz ADL), cognitive performance (Cognitive Performance Scale; CPS), pain (Pain Assessment Checklist for Seniors with Limited Ability to Communicate; PACSLAC-D), neuropsychiatric symptoms (Neuropsychiatric Inventory-Nursing Home Version; NPI-NH) and comorbidities. RESULTS: Multivariate logistic regression modelling showed associations with age in the domain Social isolation [odds ratio, OR, 0.95 (95% confidence interval, CI, 0.91-0.99)], ADL level in the domain Positive affect [OR 0.89 (95% CI 0.83-0.95)] and the domain Social relations [OR 0.87 (95% CI 0.81-0.93)], severity of dementia in the domain Social relations [OR 0.28 (95% CI 0.12-0.62)] and in the domain Social isolation [OR 2.10 (95% CI 1.17-3.78)], psychiatric disorders in the domain Positive affect [OR 0.39 (95% CI 0.17-0.87)] and pulmonary diseases in the domain Negative affect [OR 0.14 (95% CI 0.03-0.61)] of the QUALIDEM. Neuropsychiatric symptoms were independently associated with all six domains of the QUALIDEM [OR 0.93 (95% CI 0.90-0.96) to OR 0.97 (95% CI 0.95-0.99)]. Pain was associated with the domains Care relationship [OR 0.92 (95% CI 0.84-1.00)] and Negative affect [OR 0.92 (95% CI 0.85-1.00)]. CONCLUSION: QOL in dementia is independently associated with age, ADL, dementia severity, pain, psychiatric disorders, pulmonary diseases and neuropsychiatric symptoms. It is possible to detect persons with dementia at risk for a lower QOL. This information is important for developing personalized interventions to improve QOL in persons with dementia in LTCFs. PMID- 27668928 TI - RESPONSIVENESS OF THE NATIONAL EYE INSTITUTE VISUAL FUNCTION QUESTIONNAIRE-25 TO VISUAL ACUITY GAINS IN PATIENTS WITH DIABETIC MACULAR EDEMA: Evidence From the RIDE and RISE Trials. AB - PURPOSE: To evaluate the responsiveness of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with diabetic macular edema using data from the RIDE and RISE trials. METHODS: Patients were randomized to monthly intravitreal ranibizumab 0.3 mg, 0.5 mg, or sham injections for 2 years. The NEI VFQ-25 was administered at baseline and at Months 6, 12, 18, and 24. The least-squares mean change in NEI VFQ-25 for >=15 letters gained or lost was derived from analysis of covariance models. RESULTS: The mean improvement in NEI VFQ-25 composite score associated with a >=15-letter gain in best-corrected visual acuity over 24 months was 9.0 (95% confidence interval, 6.3-11.7) points in RIDE and 7.1 (95% confidence interval, 4.7-9.6) points in RISE. In patients who lost >=15 letters, the mean worsening in overall NEI VFQ-25 composite score was -6.6 (95% confidence interval, -13.6 to 0.5) in RIDE and -2.7 (95% confidence interval, -8.9 to 3.5) in RISE. CONCLUSION: This exploratory analysis of data from the RIDE and RISE studies supports the responsiveness of the NEI VFQ-25 to changes in best-corrected visual acuity over time in patients with diabetic macular edema. PMID- 27668929 TI - HYPERREFLECTIVE RETINAL SPOTS IN NORMAL AND DIABETIC EYES: B-Scan and En Face Spectral Domain Optical Coherence Tomography Evaluation. AB - PURPOSE: To evaluate hyperreflective retinal spots (HRS), in normal subjects and diabetic patients without and with macular edema (diabetic macular edema, DME), on linear B-scans and corresponding en face image of spectral-domain optical coherence tomography. METHODS: Retrospective evaluation of images of 54 eyes/subjects (16 normal subjects, 19 diabetic patients without DME, and 19 with DME). On horizontal B-scan spectral-domain optical coherence tomography, passing through the center of the fovea, the following characteristics of HRS were evaluated: location (inner retina or outer retina), size (<=30 or >30 MUm), reflectivity (similar to nerve fiber layer or to retinal pigment epithelium-Bruch complex), and presence or absence of back shadowing. On en face spectral-domain optical coherence tomography, the following patterns were evaluated: 1) isolated HRS (not corresponding to any visible lesion); 2) HRS corresponding to a segment of retinal capillary or microaneurysm wall; and 3) HRS corresponding to hard exudate. All gradings were performed twice by two graders in a masked fashion. RESULTS: Size <=30 MUm, reflectivity similar to nerve fiber layer, and absence of back shadowing were associated with absence of vessels or any other lesion on en face image (P = 0.0001 for all). Size >30 MUm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina were all associated with presence of hard exudate on en face imaging (P < 0.0001 for all). Multiple logistic regression analysis showed that HRS present in the inner retina (P < 0.0001), size >30 MUm (P = 0.0029), and presence of back shadowing (P < 0.0001) are directly associated with presence of microaneurysms on en face image. Intragrader and intergrader repeatability were excellent for all evaluations. CONCLUSION: Hyperreflective retinal spots <=30 MUm, reflectivity similar to nerve fiber layer, and absence of back shadowing may represent activated microglial cells; HRS >30 MUm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina may represent hard exudate; HRS >30 MUm, presence of back shadowing, and location in the inner retina may represent microaneurysms. These hypotheses may be tested in further studies. PMID- 27668930 TI - ANALYSIS OF PARS PLANA VITRECTOMY INCISIONS USING LIVE BACTERIA. AB - PURPOSE: To analyze small gauge pars plana vitrectomy sclerotomies using live bacteria transformed with green fluorescent protein (GFP). METHODS: Twenty-eight human cadaver eyes were specially harvested for this study. Small gauge vitrectomy was performed on each eye and the wounds were closed with various techniques (sutured, sutureless, and cauterization). Live Staphylococcus epidermidis that has been transformed with a green fluorescent protein was applied to the overlying conjunctival surface. Analysis of all vitreous samples was analyzed with confocal laser microscopy to identify the presence of bacteria. All wounds were analyzed histopathologically. RESULTS: A high concentration of bacteria was noted in 2 of 3 eyes in the sutureless, 23-G perpendicular incision group postinoculation. There were no bacteria detected in any postvitrectomy sample that were closed with cautery or a beveled incision. No bacteria were found in postvitrectomy samples of sutureless 27-G perpendicular incisions and sutureless 27-G beveled incisions. Finally, there were no bacteria detected in both eyes with 23-G perpendicular incisions that had a partial air-fill. CONCLUSION: Live bacteria can be effectively used to analyze wound integrity. Closing sclerotomy sites with cautery proved effective in a model using fresh, human cadaver eyes. 27-G perpendicular incisions may be just as competent as 27-G beveled incisions. PMID- 27668931 TI - Torpedo Maculopathy Presenting With a Vitelliform Lesion. PMID- 27668932 TI - Perfluorobutylpentane (F4H5) Solvent-Assisted Silicon Oil Removal Technique. PMID- 27668933 TI - Relationship satisfaction, PTSD symptom severity, and mental healthcare utilization among OEF/OIF veterans. AB - Despite the availability of evidence-based PTSD treatments at most facilities within the VA Healthcare System, most Iraq and Afghanistan veterans returning from deployments with posttraumatic stress symptoms do not receive an adequate dose of mental health treatment, prompting the need to identify potential barriers to or facilitators of mental health care utilization. Previous research demonstrated self-reported mental health care utilization in the prior year varies as a function of PTSD symptom severity, and the interaction of PTSD symptom severity and romantic relationship satisfaction (Meis et al., 2010). We extended these findings by objectively measuring the degree of utilization over a 1-year period (i.e., number of sessions attended) in a sample of 130 Iraq and Afghanistan veterans who presented to primary care/deployment health and completed an initial mental health evaluation. Results indicated main and interactive effects of PTSD symptom severity and relationship satisfaction, such that greater PTSD symptom severity was associated with greater utilization at average to high relationship satisfaction (p < .05), but not low relationship satisfaction. Implications for future research and couple/family based interventions for veterans with PTSD are discussed. (PsycINFO Database Record PMID- 27668934 TI - Dyadic coping and salivary interleukin-6 responses to interpersonal stress. AB - Dysregulated immune responses to stress are a potential pathway linking close relationship processes to health, and couples' abilities to cope with stress together (dyadic coping) likely impact such immune responses. Most stress research has focused on immune reactivity, whereas knowledge of immune recovery remains limited. The present study examined how acute interpersonal stress affects immune reactivity and recovery, as well as whether dyadic coping moderates these effects. Healthy couples (N = 24) completed the Dyadic Coping Inventory and provided saliva samples 4 times each day for 5 days, including 2 days before a laboratory dyadic stressor (discussing an area of disagreement), the day of, and 2 days after. Four additional saliva samples were taken throughout the laboratory stressor. Saliva samples were assayed for interleukin (IL)-6. Multilevel models that adjusted for demographic and health variables indicated that partners low in dyadic coping showed immune reactivity to the stressor whereas partners high in dyadic coping did not. Dyadic coping did not moderate immune recovery, which had occurred by 5 hr poststressor across all participants. Results suggest that partners low in dyadic coping show increased reactivity of immune responses to interpersonal stress. Enhancing dyadic coping in couples may impact not only their mental health and relationship quality, but also their risk of stress-related immune disorders. (PsycINFO Database Record PMID- 27668935 TI - Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury. AB - At low levels, carbon monoxide (CO) has physiological roles as a second messenger and neuromodulator. Here we assess the effects of CO in a mouse model of traumatic brain injury (TBI). Treatment with CO-releasing molecule (CORM)-3 reduced pericyte death and ameliorated the progression of neurological deficits. In contrast, although treatment with the radical scavenger N-tert-butyl-a phenylnitrone (PBN) also reduced pericyte death, neurological outcomes were not rescued. As compared to vehicle-treated control and PBN-treated mice, CORM-3 treated mice showed higher levels of phosphorylated neural nitric oxide synthase within neural stem cells (NSCs). Inhibition of nitric oxide synthase diminished the CORM-3-mediated increase in the number of cells that stained positive for both the neuronal marker NeuN and 5-bromo-2'-deoxyuridine (BrdU; a marker for proliferating cells) in vivo, consequently interfering with neurological recovery after TBI. Because NSCs seemed to be in close proximity to pericytes, we asked whether cross-talk between pericytes and NSCs was induced by CORM-3, thereby promoting neurogenesis. In pericyte cultures that were undergoing oxygen and glucose deprivation, conditioned cell culture medium collected after CORM-3 treatment enhanced the in vitro differentiation of NSCs into mature neurons. Taken together, these findings suggest that CO treatment may provide a therapeutic approach for TBI by preventing pericyte death, rescuing cross-talk with NSCs and promoting neurogenesis. PMID- 27668939 TI - Development of a novel in silico model of zeta potential for metal oxide nanoparticles: a nano-QSPR approach. AB - Once released into the aquatic environment, nanoparticles (NPs) are expected to interact (e.g. dissolve, agglomerate/aggregate, settle), with important consequences for NP fate and toxicity. A clear understanding of how internal and environmental factors influence the NP toxicity and fate in the environment is still in its infancy. In this study, a quantitative structure-property relationship (QSPR) approach was employed to systematically explore factors that affect surface charge (zeta potential) under environmentally realistic conditions. The nano-QSPR model developed with multiple linear regression (MLR) was characterized by high robustness [Formula: see text] and external predictivity [Formula: see text] The results clearly showed that zeta potential values varied markedly as functions of the ionic radius of the metal atom in the metal oxides, confirming that agglomeration and the extent of release of free MexOy largely depend on their intrinsic properties. A developed nano-QSPR model was successfully applied to predict zeta potential in an ionized solution of NPs for which experimentally determined values of response have been unavailable. Hence, the application of our model is possible when the values of zeta potential in the ionized solution for metal oxide nanoparticles are undetermined, without the necessity of performing more time consuming and expensive experiments. We believe that our studies will be helpful in predicting the conditions under which MexOy is likely to become problematic for the environment and human health. PMID- 27668937 TI - Efficient derivation of microglia-like cells from human pluripotent stem cells. AB - Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts, and they resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines and find that pMGLs derived from an hES model of Rett syndrome are smaller than their isogenic controls. We further describe a platform to study the integration and live behavior of pMGLs in organotypic 3D cultures. This modular differentiation system allows for the study of microglia in highly defined conditions as they mature in response to developmentally relevant cues, and it provides a framework in which to study the long-term interactions of microglia residing in a tissue like environment. PMID- 27668941 TI - A Camptocormia Case Treated With Electroconvulsive Therapy. PMID- 27668940 TI - Evidence of the Key Role of H3O+ in Phospholipid Membrane Morphology. AB - This study explains the importance of the phosphate moiety and H3O+ in controlling the ionic flux through phospholipid membranes. We show that despite an increase in the H3O+ concentration when the pH is decreased, the level of ionic conduction through phospholipid bilayers is reduced. By modifying the lipid structure, we show the dominant determinant of membrane conduction is the hydrogen bonding between the phosphate oxygens on adjacent phospholipids. The modulation of conduction with pH is proposed to arise from the varying H3O+ concentrations altering the molecular area per lipid and modifying the geometry of conductive defects already present in the membrane. Given the geometrical constraints that control the lipid phase structure of membranes, these area changes predict that organisms evolving in environments with different pHs will select for different phospholipid chain lengths, as is found for organisms near highly acidic volcanic vents (short chains) or in highly alkaline salt lakes (long chains). The stabilizing effect of the hydration shells around phosphate groups also accounts for the prevalence of phospholipids across biology. Measurement of ion permeation through lipid bilayers was made tractable using sparsely tethered bilayer lipid membranes with swept frequency electrical impedance spectroscopy and ramped dc amperometry. Additional evidence of the effect of a change in pH on lipid packing density is obtained from neutron reflectometry data of tethered membranes containing perdeuterated lipids. PMID- 27668938 TI - Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection. AB - Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI. Here we show that excess dietary zinc (Zn) substantially alters the gut microbiota and, in turn, reduces the minimum amount of antibiotics needed to confer susceptibility to CDI. In mice colonized with C. difficile, excess dietary Zn severely exacerbated C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn-binding S100 protein calprotectin has antimicrobial effects against C. difficile and is an essential component of the innate immune response to CDI. Taken together, these data suggest that nutrient Zn levels have a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile. PMID- 27668936 TI - Determinants of HIV-1 broadly neutralizing antibody induction. AB - Broadly neutralizing antibodies (bnAbs) are a focal component of HIV-1 vaccine design, yet basic aspects of their induction remain poorly understood. Here we report on viral, host and disease factors that steer bnAb evolution using the results of a systematic survey in 4,484 HIV-1-infected individuals that identified 239 bnAb inducers. We show that three parameters that reflect the exposure to antigen-viral load, length of untreated infection and viral diversity independently drive bnAb evolution. Notably, black participants showed significantly (P = 0.0086-0.038) higher rates of bnAb induction than white participants. Neutralization fingerprint analysis, which was used to delineate plasma specificity, identified strong virus subtype dependencies, with higher frequencies of CD4-binding-site bnAbs in infection with subtype B viruses (P = 0.02) and higher frequencies of V2-glycan-specific bnAbs in infection with non subtype B viruses (P = 1 * 10-5). Thus, key host, disease and viral determinants, including subtype-specific envelope features that determine bnAb specificity, remain to be unraveled and harnessed for bnAb-based vaccine design. PMID- 27668942 TI - Clozapine-Resistant Schizophrenia Treated With Ultra-brief Pulse, Unilateral Electroconvulsive Therapy. PMID- 27668943 TI - Concomitant Anticonvulsants With Bitemporal Electroconvulsive Therapy: A Randomized Controlled Trial With Clinical and Neurobiological Application. AB - BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for major affective disorders. The combined use of ECT and anticonvulsant mood stabilizers is a common clinical scenario. There is dearth of systematic studies on the use of this combination with regard to clinical or cognitive outcomes. OBJECTIVE/HYPOTHESIS: We aimed to compare clinical improvement and cognitive adverse effects between patients who received only ECT versus those who received ECT and anticonvulsants. We hypothesized that improvement would be fastest in patients who received only ECT. METHODS: We conducted a randomized controlled trial in which patients prescribed ECT while being treated with anticonvulsants were randomized into 3 groups: full-dose (FD), half-dose (HD), and stop anticonvulsant. A blind rater assessed clinical improvement in patients using rating scales [Young's Mania Rating Scale (YMRS) and Clinical Global Impression] for clinical improvement and cognitive adverse effects (Postgraduate Institute memory scale). Analysis was done using mixed-effects modeling to delineate differences in clinical and cognitive outcomes across the 3 arms of the study over the course of ECT. RESULTS: Of the 54 patients recruited, 36 patients went into treatment allocation arms per the initial randomization plan. The main anticonvulsants prescribed were sodium valproate and carbamazepine. Patients in the 3 groups were comparable on clinical features. The most common diagnosis was bipolar affective disorder-with current episode of mania. Overall, there was no difference across the 3 groups in final clinical outcome scores (YMRS and Clinical Global Impression) when analyzed as intention to treat (ITT) or "as treated." In both analyses, group * time interaction was significant when comparing trend of YMRS scores between the FD anticonvulsant group and the HD group from baseline to last ECT (P = 0.0435 in ITT and P = 0.0055 in as treated). Patients in the FD group improved faster than those in the HD group. There were no differences across the 3 groups with regard to their cognitive adverse effects in the ITT analysis; "as-treated analysis" showed the HD patients to have performed poorly on some domains. Seizure parameters showed no significant difference across the 3 groups. CONCLUSION: This is a preliminary prospective study examining whether coprescription of anticonvulsants with ECT affected clinical or cognitive outcomes. The most important takeaway point from this study is the significant reduction in YMRS scores when ECT was given with FD anticonvulsant compared with halving the dose (HD) of anticonvulsant. This difference was shown in both ITT and as-treated analysis. There is a need for more prospective studies to examine this clinical question. PMID- 27668944 TI - Factors Related to the Changes in Quality of Life for Patients With Depression After an Acute Course of Electroconvulsive Therapy. AB - OBJECTIVE: The aim of this study was to examine the effect of electroconvulsive therapy (ECT) on quality of life (QOL), depressive symptoms, and functioning for patients with depression, and to explore the variables related to QOL changes. METHODS: Ninety-five inpatients with depression receiving at least 6 ECT sessions and completed all measures were included. Quality of life, symptom severity, and functioning were assessed using Short Form 36 (SF-36), the 17-item Hamilton Rating Scale for Depression (HAMD-17), and the Modified Work and Social Adjustment Scale (MWSAS), before and after ECT. The SF-36 includes 8 subscales, physical component summary (PCS), and mental component summary (MCS). Adverse effects after ECT, including headache, muscle pain, and nausea/vomiting, were also recorded. RESULTS: All 8 SF-36 subscales, PCS, MCS, HAMD-17, and MWSAS improved significantly after treatment. Using multiple linear regression analysis, MWSAS changes predicted PCS changes significantly after adjusting for baseline PCS. Similarly, using multiple linear regression analysis, MWSAS changes were significant variables associated with MCS changes after adjusting for ECT frequency, HAMD-17 changes, and baseline MCS. The ECT improved QOL, depressive symptoms, and functioning. CONCLUSIONS: Whether strategies to enhance functioning during an acute course of ECT could improve QOL is needed to be examined in a further study. PMID- 27668946 TI - Ti3+-Promoted High Oxygen-Reduction Activity of Pd Nanodots Supported by Black Titania Nanobelts. AB - One-dimensional nanocrystals favoring efficient charge transfer have attracted enormous attentions, and conductive nanobelts of black titania with a unique band structure and high electrical conductivity would be interestingly used in electrocatalysis. Here, Pd nanodots supported by two kinds of black titania, the oxygen-deficient titania (TiO2-x) and nitrogen-doped titania (TiO2-x:N), were synthesized as efficient composite catalysts for oxygen-reduction reaction (ORR). These composite catalysts show improved catalytic activity with lower overpotential and higher limited current, compared to the Pd nanodots supported on the white titania (Pd/TiO2). The improved activity is attributed to the relatively high conductivity of black titania nanobelts for efficient charge transfer (CT) between Ti3+ species and Pd nanodots. The CT process enhances the strong metal-support interaction (SMSI) between Pd and TiO2, which lowers the absorption energy of O2 on Pd and makes it more suitable for oxygen reduction. Because of the stronger interaction between Pd and support, the Pd/TiO2-x:N also shows excellent durability and immunity to methanol poisoning. PMID- 27668947 TI - Building Better Systems for Stroke: The Time Is Now. PMID- 27668945 TI - Cell cycle controls stress response and longevity in C. elegans. AB - Recent studies have revealed a variety of genes and mechanisms that influence the rate of aging progression. In this study, we identified cell cycle factors as potent regulators of health and longevity in C. elegans. Focusing on the cyclin dependent kinase 2 (cdk-2) and cyclin E (cye-1), we show that inhibition of cell cycle genes leads to tolerance towards environmental stress and longevity. The reproductive system is known as a key regulator of longevity in C. elegans. We uncovered the gonad as the central organ mediating the effects of cell cycle inhibition on lifespan. In particular, the proliferating germ cells were essential for conferring longevity. Steroid hormone signaling and the FOXO transcription factor DAF-16 were required for longevity associated with cell cycle inhibition. Furthermore, we discovered that SKN-1 (ortholog of mammalian Nrf proteins) activates protective gene expression and induces longevity when cell cycle genes are inactivated. We conclude that both, germline absence and inhibition through impairment of cell cycle machinery results in longevity through similar pathways. In addition, our studies suggest further roles of cell cycle genes beyond cell cycle progression and support the recently described connection of SKN-1/Nrf to signals deriving from the germline. PMID- 27668949 TI - E-Cigarettes, Youth, and the US Food and Drug Administration's "Deeming" Regulation. PMID- 27668948 TI - Improving Access to Effective Care for People With Mental Health and Substance Use Disorders. PMID- 27668950 TI - Merging Structural Information from X-ray Crystallography, Quantum Chemistry, and EXAFS Spectra: The Oxygen-Evolving Complex in PSII. AB - Structural data of the oxygen-evolving complex (OEC) in photosystem II (PSII) determined by X-ray crystallography, quantum chemistry (QC), and extended X-ray absorption fine structure (EXAFS) analyses are presently inconsistent. Therefore, a detailed study of what information can be gained about the OEC through a comparison of QC and crystallographic structure information combined with the information from range-extended EXAFS spectra was undertaken. An analysis for determining the precision of the atomic coordinates of the OEC by QC is carried out. OEC model structures based on crystallographic data that are obtained by QC from different research groups are compared with one another and with structures obtained by high-resolution crystallography. The theory of EXAFS spectra is summarized, and the application of EXAFS spectra to the experimental determination of the structure of the OEC is detailed. We discriminate three types of parameters entering the formula for the EXAFS spectrum: (1) model independent, predefined, and fixed; (2) model-dependent that can be computed or adjusted; and (3) model-dependent that must be adjusted. The information content of EXAFS spectra is estimated and is related to the precision of atomic coordinates and resolution power to discriminate different atom-pair distances of the OEC. It is demonstrated how a precise adjustment of atomic coordinates can yield a nearly perfect representation of the experimental OEC EXAFS spectrum, but at the expense of overfitting and losing the knowledge of the initial OEC model structure. Introducing a novel type of penalty function, it is shown that moderate adjustment of atomic coordinates to the EXAFS spectrum limited by constraints avoids overfitting and can be used to validate different OEC model structures. This technique is used to identify the OEC model structures whose computed OEC EXAFS spectra agree best with the measured spectrum. In this way, the most likely S-state and protonation pattern of the OEC for the most recent high-resolution crystal structure of PSII are determined. We find that the X-ray free-electron laser (XFEL) structure is indeed not significantly affected by exposure to XFEL pulses and thus results in a radiation-damage-free model of the OEC. PMID- 27668951 TI - Mueller matrix approach for probing multifractality in the underlying anisotropic connective tissue. AB - Spatial variation of refractive index (RI) in connective tissues exhibits multifractality, which encodes useful morphological and ultrastructural information about the disease. We present a spectral Mueller matrix (MM)-based approach in combination with multifractal detrended fluctuation analysis (MFDFA) to exclusively pick out the signature of the underlying connective tissue multifractality through the superficial epithelium layer. The method is based on inverse analysis on selected spectral scattering MM elements encoding the birefringence information on the anisotropic connective tissue. The light scattering spectra corresponding to the birefringence carrying MM elements are then subjected to the Born approximation-based Fourier domain preprocessing to extract ultrastructural RI fluctuations of anisotropic tissue. The extracted RI fluctuations are subsequently analyzed via MFDFA to yield the multifractal tissue parameters. The approach was experimentally validated on a simple tissue model comprising of TiO2 as scatterers of the superficial isotropic layer and rat tail collagen as an underlying anisotropic layer. Finally, the method enabled probing of precancer-related subtle alterations in underlying connective tissue ultrastructural multifractality from intact tissues. PMID- 27668952 TI - Evaluation of Raman spectroscopy in comparison to commonly performed dengue diagnostic tests. AB - This study demonstrates the evaluation of Raman spectroscopy as a rapid diagnostic test in comparison to commonly performed tests for an accurate detection of dengue fever in human blood sera. Blood samples of 104 suspected dengue patients collected from Holy Family Hospital, Rawalpindi, Pakistan, have been used in this study. Out of 104 samples, 52 (50%) were positive based on immunoglobulin G (IgG), whereas 54 (52%) were positive based on immunoglobulin M (IgM) antibody tests. For the determination of the diagnostic capabilities of Raman spectroscopy, accuracy, sensitivity, specificity and false positive rate have been calculated in comparison to normally performed IgM and IgG captured enzyme-linked immunosorbent assay tests. Accuracy, precision, specificity, and sensitivity for Raman spectroscopy in comparison to IgM were found to be 66%, 70%, 72%, and 61%, whereas based on IgG they were 47%, 46%, 52%, and 43%, respectively. PMID- 27668953 TI - Milestones and Competency-Based Medical Education in Internal Medicine. PMID- 27668954 TI - Endocrine-Disrupting Chemicals. PMID- 27668956 TI - Significant haze after photorefractive keratectomy in a cornea with previous arcuate keratotomy: June consultation #1. PMID- 27668957 TI - June consultation #2. PMID- 27668955 TI - Systems Strategies for Health Throughout the Life Course. PMID- 27668958 TI - June consultation #3. PMID- 27668959 TI - June consultation #4. PMID- 27668960 TI - June consultation #5. PMID- 27668961 TI - June consultation #6. PMID- 27668962 TI - June consultation #7. PMID- 27668963 TI - Isolation, Structure Elucidation, and Absolute Configuration of Highly Oxygenated Germacranolides from Carpesium cernuum. AB - The new highly oxygenated germacranolides cernuumolides A-J (1-10) and the known compounds 11-20 were isolated from Carpesium cernuum. Among these compounds, 1-4 are 11-methoxymethylgermacranolides and 5-7 as well as 11-17 are 2,9-hemiacetal linked germacranolides. Their structures were elucidated using NMR and HRESIMS analyses, and X-ray diffraction studies were used to confirm the absolute configurations of 1, 2, 5, 6, 8, and 9. Cernuumolides A-J were evaluated for their in vitro cytotoxicity against the A549, HCT116, MDA-MB-231, and BEL7404 cell lines, and 8 exhibited moderate cytotoxicity with IC50 values in the 0.87 2.02 MUM range. PMID- 27668964 TI - A Nanoscale Tool for Photoacoustic-Based Measurements of Clotting Time and Therapeutic Drug Monitoring of Heparin. AB - Heparin anticoagulation therapy is an indispensable feature of clinical care yet has a narrow therapeutic window and is the second most common intensive care unit (ICU) medication error. The active partial thromboplastin time (aPTT) monitors heparin but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to dose. Here, we describe a photoacoustic imaging technique to monitor heparin concentration using methylene blue as a simple and Federal Drug Administration approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood. Clinically relevant heparin concentrations were detected in blood in 32 s with a detection limit of 0.28 U/mL. We validated this imaging approach by correlation to the aPTT (Pearson's r = 0.86; p < 0.05) as well as with protamine sulfate treatment. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 MUg/mL. We then used these findings to create a nanoparticle-based hybrid material that can immobilize methylene blue for potential applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first use of photoacoustics to image anticoagulation therapy with significant potential implications to the cardiovascular and surgical community. PMID- 27668966 TI - Discovery of a Small-Molecule Inhibitor of Protein-MicroRNA Interaction Using Binding Assay with a Site-Specifically Labeled Lin28. AB - MicroRNAs (miRNAs) regulate gene expression by targeting protein-coding transcripts that are involved in various cellular processes. Thus, miRNA biogenesis has been recognized as a novel therapeutic target. Especially, the let 7 miRNA family is well-known for its tumor suppressor functions and is downregulated in many cancer cells. Lin28 protein binds to let-7 miRNA precursors to inhibit their maturation. Herein, we developed a FRET-based, high-throughput screening system to identify small-molecule inhibitors of the Lin28-let-7 interaction. We employed unnatural amino acid mutagenesis and bioorthogonal chemistry for the site-specific fluorescent labeling of Lin28, which ensures the robustness and reliability of the FRET-based protein-miRNA binding assay. Using this direct binding assay, we identified an inhibitor of the oncogenic Lin28-let 7 interaction. The inhibitor enhanced the production of let-7 miRNAs in Lin28 expressing cancer cells and reduced the level of let-7 target oncogene products. PMID- 27668965 TI - Oxidative Damage of Biomolecules by the Environmental Pollutants NO2* and NO3*. AB - Air pollution is responsible for the premature death of about 7 million people every year. Ozone (O3) and nitrogen dioxide (NO2*) are the key gaseous pollutants in the troposphere, which predominantly result from combustion processes. Their inhalation leads to reactions with constituents in the airway surface fluids (ASF) of the respiratory tract and/or lungs. ASF contain small molecular-weight antioxidants, which protect the underlying epithelial cells against oxidative damage. When this defense system is overwhelmed, proteins and lipids present on cell surfaces or within the ASF become vulnerable to attack. The resulting highly reactive protein and lipid oxidation products could subsequently damage the epithelial cells through secondary reactions, thereby causing inflammation. While reactions of NO2* with biological molecules are considered to proceed through radical pathways, the biological effect of O3 is attributed to its high reactivity with pi systems. Because O3 and NO2* always coexist in the polluted ambient atmosphere, synergistic effects resulting from in situ formed strongly oxidizing nitrate radicals (NO3*) may also require consideration. For example, in vitro product studies revealed that phenylalanine, which is inert not only to oxidants produced through biochemical processes, but also to NO2* or O3 in isolation, is damaged by NO3*. The reaction is initiated by oxidation of the aromatic ring and, depending on the availability of NO2*, leads to formation of nitrophenylalanine or beta-nitrooxyphenylalanine, which could serve as marker for NO3*-induced oxidative damage in peptides. More easily oxidizable aromatic amino acids are directly attacked by NO2* and are converted to the same products independent of whether O3 is also present. Remarkably, NO2*-induced oxidative damage in peptides occurs not only through the well-established radical oxidation of peptide side chains, but also through an unprecedented fragmentation/rearrangement of the peptide backbone. This process is initiated by a nonradical N-nitrosation of a peptide bond involving the dimer of NO2*, i.e., N2O4, and contracts the peptide chain in the N -> C direction by expelling one amino acid residue with simultaneous fusion of the remaining molecular termini, thereby forming a new peptide bond. This peptide cleavage could potentially be highly relevant for peptide segments with "nonvulnerable" side chains closer to the terminus that are not tied up in complex secondary and tertiary structures and therefore accessible for environmental oxidants. Likewise, NO2* reacts with cholesterol at the C?C moiety through an ionic mechanism, which leads to formation of 6-nitrocholesterol in the presence of moisture. Contrary to common belief, this clearly shows that ionic chemistry, in particular nitrosation reactions by intermediately formed NO+, requires consideration when assessing NO2* toxicity. This conclusion is supported by recent work by Colussi et al. (Enami, S.; Hoffmann, M. R.; Colussi, A. J. Absorption of inhaled NO2. J. Phys. Chem. B. 2009, 113, 7977-7981), who showed that anions in the airway surfaces fluids mediate NO2* absorption by catalyzing its hydrolytic disproportionation into NO2-/HNO2 and NO3-. These findings could be the key to our understanding why NO2*, despite its low water solubility, has such pronounced biological effects in vivo. PMID- 27668967 TI - Achieving High Energy Density in PVDF-Based Polymer Blends: Suppression of Early Polarization Saturation and Enhancement of Breakdown Strength. AB - Polymers with high dielectric strength and favorable flexibility have been considered promising materials for dielectrics and energy storage applications, while the achievable energy density (Ue) of polymer is rather limited by the intrinsic low dielectric constant and ferroelectric hysteresis. Polyvinylidene fluoride-trifluoroethylene-chlorofluoroethylene (P(VDF-TrFE-CFE)) with ultrahigh epsilonr of >50 is considered promising in achieving high Ue of polymer dielectrics. However, P(VDF-TrFE-CFE) only exhibits moderate Ue due to the early saturation of electrical polarization at low electric field. In this contribution, we show that, by blending P(VDF-TrFE-CFE) with polyvinylidene fluoride (PVDF), the early saturation of P(VDF-TrFE-CFE) is substantially suppressed, giving rise to concomitant enhancement of dielectric permittivity and breakdown strength. An ultrahigh energy density of 19.6 J/cm3 is thus achieved at ~640 kV/mm, which is 1600% greater than Ue of the benchmark biaxially oriented polypropylene (BOPP, 1.2 J/cm3 at 640 kV/mm). Results of phase field simulations reveal that the interfaces between PVDF and P(VDF-TrFE-CFE) play a critical role by not only suppressing early saturation of electrical polarization in P(VDF-TrFE CFE) but also inducing additional interfacial polarization. Binary phase diagram of P(VDF-TrFE-CFE)/PVDF blends is also systematically explored with their dielectric and energy storage behavior studied. PMID- 27668969 TI - The Grim Reaper, Hounds of Hell, and Dr. Death: The Role of Storytelling for Palliative Care in Competing Medical Meaning Systems. AB - Palliative care (PC) is a medical specialty that strives to fulfill the physical, psychosocial, emotional, practical, and spiritual needs of individuals at end of life or in tandem with curative treatment. Although exponentially rising in use and beneficial to patient well-being at end of life, the purpose of PC is often misunderstood and those providing its services frequently report resistance from organizational members. Such resistance can be attributed to tensions between traditional biomedical models of medicine that privilege curative treatment and biosocial models of medicine that holistically care for patients. Thus, this study addresses what tensions PC providers experience in their institutions and what communicative strategies they use at the interpersonal level in managing those tensions. Using structuration theory in tandem with relational dialectics theory, we inductively analyzed semistructured interviews with 24 Circle of Life award-winning PC providers. Findings indicate two dialectics experienced by PC providers in their institutions: the living-dying dialectic and the practicing advocating dialectic. We conclude that these interpersonal dialectics emerge through interaction in competing medical meaning systems and found that storytelling was a particularly salient form of communication that participants used for management. PMID- 27668968 TI - Water-Soluble and Highly Luminescent Europium(III) Complexes with Favorable Photostability and Sensitive pH Response Behavior. AB - Two highly luminescent and water-soluble Eu(III) complexes, Eu1 and Eu2, based on novel carboxyl-functionalized 1,5-naphthyridine derivatives 8-hydroxy-1,5 naphthyridine-2-carboxylic acid (H2L1) and 7-cyano-8-hydroxy-1,5-naphthyridine-2 carboxylic acid (H2L2), respectively, are designed and synthesized. The crystal structure of Eu2 indicates that the central Eu(III) ion is nine-coordinated by three tridentate ligands (O^N^O). Both Eu1 and Eu2 show strong luminescence in aqueous solution with quantum yields (lifetimes) of 28% (1.1 ms) and 14% (0.76 ms), respectively. The chelates display unique UV-light stability in solution and remain highly emissive after 100 min of strong UV irradiation (~300 W.m-2 at 345 nm). Moreover, they exhibit reversible luminescence intensity changes with varied pH values, and the response mechanism is investigated. "Turn-on" of the Eu(III) emission upon increasing pH is realized by ligand structure change from keto to enol anion form, resulting in red-shifted absorption band and suppressed quenching from solvents and N-H vibration upon deprotonating. The results show that these novel Eu(III) complexes are quite intriguing for potential application as bioimaging agents and pH probes. PMID- 27668970 TI - Integrating the Principles of Socioecology and Critical Pedagogy for Health Promotion Health Literacy Interventions. AB - While health literacy research has experienced tremendous growth in the last two decades, the field still struggles to devise interventions that lead to lasting change. Most health literacy interventions are at the individual level and focus on resolving clinician-patient communication difficulties. As a result, the interventions use a deficit model that treats health literacy as a patient problem that needs to be fixed or circumvented. We propose that public health health literacy interventions integrate the principles of socioecology and critical pedagogy to develop interventions that build capacity and empower individuals and communities. Socioecology operates on the premise that health outcome is hinged on the interplay between individuals and their environment. Critical pedagogy assumes education is inherently political, and the ultimate goal of education is social change. Integrating these two approaches will provide a useful frame in which to develop interventions that move beyond the individual level. PMID- 27668971 TI - Serum B-cell activating factor predicts prognosis in nasal type, extranodal NK/T cell lymphoma. AB - B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells. However, the relationship between BAFF and ENKTCL has not been reported. Here we proposed a hypothesis that BAFF might play a regulatory role in ENKTCL development and maintenance. Our results showed that serum BAFF in ENKTCL patients was significantly higher than that in control group and negatively correlated with patients' survival. It may be a valuable prognostic factor and deserved further study. PMID- 27668972 TI - Antenatal glucocorticoids and neonatal inflammation-associated proteins. AB - BACKGROUND: To date, studies of the relationship between antenatal glucocorticoids (AGC) and neonatal inflammation in preterm newborns have been largely limited to umbilical cord blood specimens. AIM: To explore the association between exposure to antenatal glucocorticoids and concentrations of inflammation-related proteins in whole blood collected from very preterm newborns at multiple times during the first postnatal month. METHODS: We measured the protein concentrations on postnatal day 1 (N=1118), day 7 (N=1138), day 14 (N=1030), day 21 (N=936) and day 28 (N=877) from infants born before the 28th week of gestation and explored the relationship between antenatal steroid receipt and protein concentrations in the highest and lowest quartiles. The creation of multinomial logistic regression models (adjusted for potential confounders) allowed us calculate odds ratios and 95% confidence intervals. RESULTS: Twenty of 420 assessments [21 (proteins)*2 (exposure levels: partial and full)*2 (quartile levels: top and bottom)*5 (days)] were statistically significant without any cohesive pattern. CONCLUSION: Among infants born before 28 weeks of gestational age, neither full, nor partial courses of antenatal glucocorticoids have a sustained anti-inflammatory effect. PMID- 27668973 TI - Evaluation of a Mobile Health Approach to Tuberculosis Contact Tracing in Botswana. AB - Tuberculosis (TB) contact tracing is typically conducted in resource-limited settings with paper forms, but this approach may be limited by inefficiencies in data collection, storage, and retrieval and poor data quality. In Botswana, we developed, piloted, and evaluated a mobile health (mHealth) approach to TB contact tracing that replaced the paper form-based approach for a period of six months. For both approaches, we compared the time required to complete TB contact tracing and the quality of data collected. For the mHealth approach, we also administered the Computer System Usability Questionnaire to 2 health care workers who used the new approach, and we identified and addressed operational considerations for implementation. Compared to the paper form-based approach, the mHealth approach reduced the median time required to complete TB contact tracing and improved data quality. The mHealth approach also had favorable overall rating, system usefulness, information quality, and interface quality scores on the Computer System Usability Questionnaire. Overall, the mHealth approach to TB contact tracing improved on the paper form-based approach used in Botswana. This new approach may similarly benefit TB contact tracing efforts in other resource limited settings. PMID- 27668976 TI - Population-based norms in crisis. PMID- 27668974 TI - A Study of VITOM in Pediatric Surgery and Urology: Evaluation of Technology Acceptance and Usability by Operating Team and Surgeon Musculoskeletal Discomfort. AB - INTRODUCTION: We studied operating team acceptability of Video Telescopic Monitor (VITOM(r)) exoscope by exploring the ease of use of the device in two centers. We also assessed factors affecting surgeon musculoskeletal discomfort. METHODS: We focused on how the operating team interacted with the VITOM system with surrogate measures of usefulness, image quality, ease of use, workload, and setup time. Multivariable linear regression was used to model the relationships between team role, experience, and setup time. Relationships between localized musculoskeletal discomfort and use of VITOM alone, and with loupes, were also analyzed. RESULTS: Four surgeons, 7 surgical techs, 7 circulating nurses, and 13 surgical residents performed 70 pediatric surgical and urological operations. We found that subjective views of each team member were consistently positive with 69%-74% agreed or strongly agreed that VITOM enhanced their ability to perform their job and improved the surgical process. Unexpectedly, the scrub techs and nurses perceived more value and utility of VITOM, presumably because it provides them a view of the operative field that would otherwise be unavailable to them. Team members rated perceptions of image quality highly and workload generally satisfactory. Not surprisingly, setup time decreased with team experience and multivariable modeling showed significant correlations with surgeon and surgical tech experience, but not circulating nurse. An important finding was that surgeon neck discomfort was reduced with use of VITOM alone for magnification, compared with use of loupes and VITOM. The most likely explanation for these findings is improved posture with the neck at a neutral position when viewing the VITOM images, compared with neck flexion with loupes, and thus, a less favorable ergonomic position. CONCLUSION: This study suggests that there may be small drawbacks associated with VITOM use initially, but these reduce with increased experience and benefit both the surgeon and the rest of the team. PMID- 27668975 TI - Discharge Education on Maternal Morbidity and Mortality Provided by Nurses to Women in the Postpartum Period. AB - OBJECTIVE: To explore what types of educational materials and discharge information are currently used by postpartum nurses to educate women about the warning signs of postpartum complications to determine what key messages should be presented to women after birth and before discharge. DESIGN: Exploratory qualitative. SETTING: Six hospitals located in New Jersey and Georgia. PARTICIPANTS: Fifty-two nurses. METHODS: Six focus group discussions were conducted using a semistructured interview guide to elicit data on how and what nurses taught women about maternal post-birth warning signs. The focus group discussions were audiotaped, transcribed, coded, and clustered into categories. RESULTS: Most nurses described some of the warning signs related to maternal morbidity and mortality to the women; however, these elements were not the primary focus of the education throughout the hospital stay and were most often discussed on the day of discharge. Nurses also did not consistently describe the same signs and symptoms of the warning signs with each and every woman. The primary mechanism for education consisted of individualized instruction with booklets or folders of information. CONCLUSION: These data indicate that improvements may be needed in how nurses educate women who just gave birth about the most common post-birth warning signs before they are discharged from the hospital. These findings also suggest that nurses need more information and guidance on how to teach all women about the post-birth warning signs. PMID- 27668977 TI - A new assessment tool for patients with multiple sclerosis from Spanish-speaking countries: validation of the Brief International Cognitive Assessment for MS (BICAMS) in Argentina. AB - BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is an international assessment tool for monitoring cognitive function in multiple sclerosis (MS) patients. BICAMS comprises the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test - Second Edition (CVLT II) and the Brief Visuospatial Memory Test - Revised (BVMT-R). Our objective was to validate and assess the reliability of BICAMS as applied in Argentina and to obtain normative data in Spanish for this population. METHOD: The sample composed of 50 MS patients and 100 healthy controls (HC). In order to test its reliability, BICAMS was re-administered in a subset of 25 patients. RESULTS: The sample's average age was 43.42 +/- 10.17 years old, and average years of schooling were 14.86 +/- 2.78. About 74% of the participants were women. The groups did not differ in age, years of schooling, or gender. The MS group performed significantly worse than the HC group across the three neuropsychological tests, yielding the following Cohen's d values: SDMT: .85; CVLT I: .87; and BVMT-R: .40. The mean raw scores for Argentina normative data were as follows: SDMT: 56.71 +/- 10.85; CVLT I: 60.88 +/- 10.46; and BVMT-R: 23.44 +/- 5.84. Finally, test-retest reliability coefficients for each test were as follows: SDMT: r = .95; CVLT I: r = .87; and BVMT-R: r = .82. CONCLUSION: This BICAMS version is reliable and useful as a monitoring tool for identifying MS patients with cognitive impairment. PMID- 27668978 TI - Ultrasound versus MRI in common fibular neuropathy. AB - INTRODUCTION: We prospectively compared ultrasound (US) and MRI in patients with common fibular neuropathy. METHODS: Forty adult patients with clinical suspicion of common fibular neuropathy and 40 healthy controls underwent both US and MRI. US and MRI datasets were randomized for prospective reading. RESULTS: The overall sensitivity of US and MRI for diagnosing fibular neuropathy was 90% (95% confidence interval [CI], 79.7%-97.3%) and 87.5% (95% CI, 71.55%-93.1%), respectively. The overall specificity of US and MRI was 92% (95% CI, 77.45% 96.1%) and 85% (95% CI, 73.3%-94.4%), respectively. The overall sensitivity and specificity of US combined with MRI were 94% (95% CI, 0.80%-0.99%) and 84% (95% CI, 0.70%-0.91%), respectively. Overall intra- and inter-observer agreements among 3 readers were 0.76% (95% CI, 0.62%-0.85%) and 0.74% (95% CI, 0.65%-0.81%). CONCLUSIONS: US diagnostic accuracy for common fibular neuropathy was slightly higher than that of MRI. Muscle Nerve 55: 849-857, 2017. PMID- 27668979 TI - ERG6 gene deletion modifies Kluyveromyces lactis susceptibility to various growth inhibitors. AB - The ERG6 gene encodes an S-adenosylmethionine dependent sterol C-24 methyltransferase in the ergosterol biosynthetic pathway. In this work we report the results of functional analysis of the Kluyveromyces lactis ERG6 gene. We cloned the KlERG6 gene, which was able to complement the erg6Delta mutation in both K. lactis and Saccharomyces cerevisiae. The lack of ergosterol in the Klerg6 deletion mutant was accompanied by increased expression of genes encoding the last steps of the ergosterol biosynthesis pathway as well as the KlPDR5 gene encoding an ABC transporter. The Klerg6Delta mutation resulted in reduced cell susceptibility to amphotericin B, nystatin and pimaricin and increased susceptibility to azole antifungals, fluphenazine, terbinafine, brefeldin A and caffeine. The susceptibility phenotype was suppressed by the KlPDR16 gene encoding one of the phosphatidylinositol transfer proteins belonging to the Sec14 family. Decreased activity of KlPdr5p in Klerg6Delta mutant (measured as the ability to efflux rhodamine 6G) together with increased amount of KlPDR5 mRNA suggest that the zymosterol which accumulates in the Klerg6Delta mutant may not fully compensate for ergosterol in the membrane targeting of efflux pumps. These results point to the fact that defects in sterol transmethylation appear to cause a multitude of physiological effects in K. lactis cells. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27668980 TI - VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population. AB - The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos. PMID- 27668981 TI - Stability of FeNO and airway hyperresponsiveness to mannitol in untreated asthmatics. AB - OBJECTIVE: Airway hyperresponsiveness and airway inflammation are important hallmarks of asthma and are useful in asthma diagnosing, monitoring and treatment. The aim of the study was to assess whether two commonly used clinical tests, the mannitol challenge and Fraction of exhaled NO (FeNO), were stable clinical indicators over time in stable untreated asthmatics. METHODS: 54 non smoking, asthma patients not treated with steroids were enrolled in the study and assessed at baseline and a median of 6 months later. At baseline and follow-up, FeNO and airway hyperesponsiveness to mannitol were measured, and asthma control was assessed with the Asthma Control Questionnaire (ACQ). RESULTS: A total of 41 subjects completed both visits. Mean (SD) FEV1% at baseline was 94.1% (17.7) and at re-examination 94.6% (19.7) (ns). The ACQ score was unchanged from baseline (Mean (SD): 0.90 (+/- 0.73)) to follow-up 0.90 (+/- 0.74) (ns), as was the FEV1% (94.1% (+/-17.1%) vs 94.6% (19.7%)(ns) indicating that patients were clinically stable during follow-up. The response to mannitol was unchanged at follow-up (Geometric mean (CI) of Response Dose Ratio (RDR) to mannitol: 0.026(0.013-0.046) vs 0.026(0.012-0.050) (ns). There was a slight decrease in FeNO at follow-up (25.5 ppb (19.7-32.9) to 21.9 ppb (17.1-28.2) (p < 0.001). CONCLUSIONS: In steroid-free non-smoking asthmatics with constant symptom scores and lung function, airway responsiveness to mannitol remained at the same level over a period of months, while a minor change in exhaled FeNO was reported. These results suggest that mannitol is a stable, reliable marker of clinical disease activity. PMID- 27668982 TI - Differences in Symptom Distress Based on Gender and Palliative Care Designation Among Hospitalized Patients. AB - PURPOSE: To explore patient-reported symptom distress in relation to documentation of symptoms and palliative care designation in hospital inpatients. DESIGN: This cross-sectional study analyzed data from 710 inpatients at two large hospitals in Sweden using the Edmonton Symptom Assessment Scale and the Memorial Symptom Assessment Scale. Chart reviews focused on nurses' and physicians' symptom documentation and palliative turning point. METHODS: Descriptive statistics were calculated for all variables and provided summaries about the sample. Patients were grouped according to gender, age, palliative care designation, and symptom documentation. The t test and chi-square test were used to calculate whether symptom distress varied between groups. A two-way analysis of variance was conducted for multiple comparisons to explore the impact of gender and age on mean symptom distress. FINDINGS: Females reported higher levels of symptom distress than did males related to pain, fatigue, and nausea. When comparing symptom distress between males and females with documentation pertaining to symptoms, there were significant differences implying that females had to report higher levels of symptom distress than males in order to have their symptoms documented. CONCLUSIONS: Females need to report higher levels of symptom distress than do males for healthcare professionals to identify and document their symptoms. It can be hypothesized that females are not receiving the same attention and symptom alleviation as men. If so, this highlights a serious inequality in care that requires further exploration. CLINICAL RELEVANCE: Considering that common reasons why people seek health care are troublesome symptoms of illness, and that the clinical and demographic characteristics of inpatients are changing towards more advanced ages with serious illnesses, inadequate symptom assessment and management are a serious threat to the care quality. PMID- 27668983 TI - CAZyme content of Pochonia chlamydosporia reflects that chitin and chitosan modification are involved in nematode parasitism. AB - Pochonia chlamydosporia is a soil fungus with a multitrophic lifestyle combining endophytic and saprophytic behaviors, in addition to a nematophagous activity directed against eggs of root-knot and other plant parasitic nematodes. The carbohydrate-active enzymes encoded by the genome of P. chlamydosporia suggest that the endophytic and saprophytic lifestyles make use of a plant cell wall polysaccharide degradation machinery that can target cellulose, xylan and, to a lesser extent, pectin. This enzymatic machinery is completed by a chitin breakdown system that involves not only chitinases, but also chitin deacetylases and a large number of chitosanases. P. chlamydosporia can degrade and grow on chitin and is particularly efficient on chitosan. The relevance of chitosan breakdown during nematode egg infection is supported by the immunolocalization of chitosan in Meloidogyne javanica eggs infected by P. chlamydosporia and by the fact that the fungus expresses chitosanase and chitin deacetylase genes during egg infection. This suggests that these enzymes are important for the nematophagous activity of the fungus and they are targets for improving the capabilities of P. chlamydosporia as a biocontrol agent in agriculture. PMID- 27668985 TI - Severe Traumatic Brain Injury In Children: An Evidence-Based Review Of Emergency Department Management. AB - More than 1.7 million traumatic brain injuries occur in adults and children each year in the United States, with approximately 30% occurring in children aged < 14 years. Traumatic brain injury is a significant cause of morbidity and mortality in pediatric trauma patients. Early identification and management of severe traumatic brain injury is crucial in decreasing the risk of secondary brain injury and optimizing outcome. The main focus for early management of severe traumatic brain injury is to mitigate and prevent secondary injury, specifically by avoiding hypotension and hypoxia, which have been associated with poorer outcomes. This issue discusses methods to maintain adequate oxygenation, maximize management of intracranial hypertension, and optimize blood pressure in the emergency department to improve neurologic outcomes following pediatric severe traumatic brain injury. PMID- 27668984 TI - Deletion of AMPKalpha1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release. AB - BACKGROUND AND PURPOSE: Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. EXPERIMENTAL APPROACH: Endothelium denuded aortic rings from wild-type (WT; Sv129) and alpha1 AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPKalpha1 KO on the secretory profile of PVAT was assessed by elisa. KEY RESULTS: Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. CONCLUSIONS AND IMPLICATIONS: AMPKalpha1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. LINKED ARTICLES: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. PMID- 27668986 TI - Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population. AB - The familial aggregation indicated the inheritance of cancer risk. Recent genome wide association studies (GWASs) have identified a number of common single nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (LC) (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for hepatitis B virus-related hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250 kb or 500 kb upward and downward of the GWAS-reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for LC (R2 = 0.641, p = 0.001) and esophageal squamous cell cancer (R2 = 0.633, p = 0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese. PMID- 27668987 TI - Ingredients for a Dutch radon action plan, based on a national survey in more than 2500 dwellings. AB - A new Euratom directive demands that Member States establish a national action plan for indoor radon. Important requirements are a national reference level for the radon concentration in dwellings, actions to identify dwellings with radon concentrations that might exceed this reference level and the encouragement of appropriate measures to reduce the radon concentrations in dwellings where these are high. This paper provides ingredients and recommendations for a national action plan for radon in dwellings, applicable to the Netherlands. The approach presented here, which may serve as a model for other countries or regions with a comparatively favourable indoor radon situation, is based on the analysis of radon data from a national survey in more than 2500 Dutch dwellings, built since 1930. The annual average activity concentration of radon in dwellings in the Netherlands equals 15.6 +/- 0.3 Bq m-3. The 50th and 95th percentiles were found to be 12.2 and 38.0 Bq m-3, respectively. In 0.4 per cent of the dwellings we found values above 100 Bq m-3. Radon concentrations showed correlations with type of dwelling, year of construction, ventilation system, soil type and smoking behaviour of inhabitants. The survey data suggest that it is feasible for the Netherlands to adopt a national reference level for radon in dwellings of 100 Bq m-3, in line with recommendations by WHO and ICRP. We were able to predict dwellings with a moderate probability for radon concentrations above 100 Bq m-3 by applying a combination of three selection criteria: location, type of dwelling and manner of ventilation. Of the existing 6.2 million dwellings in the Netherlands (built since 1930), approximately 23-24 thousand are suspected to exceed this level. Some 80% of these are found in the group of naturally ventilated single-family dwellings in either the southern part of Limburg (approx. 13 thousand) or the Meuse-Rhine-Waal river delta (approx. six thousand). This selected group of dwellings represents 7% of the housing stock. In contrast to many other countries in Europe and elsewhere, radon concentrations in dwellings above 200 Bq m-3 are very rare in the Netherlands. As a result, relatively simple and inexpensive measures in existing Dutch single-family dwellings will be sufficient to reduce indoor radon concentrations above the proposed national reference level of 100 Bq m-3 to values well below. PMID- 27668988 TI - Internet-delivered cognitive behavior therapy for children and adolescents: A systematic review and meta-analysis. AB - Internet-delivered cognitive behavior therapy (ICBT) is a relatively novel treatment format with the potential to increase accessibility of evidence-based care. However, little is known about the feasibility and efficacy of ICBT in children and adolescents. We conducted a comprehensive systematic review and meta analysis of ICBT for children and adolescents to provide an overview of the field and assess the efficacy of these interventions. A systematic literature search of six electronic databases was performed to identify ICBT intervention studies for children with a psychiatric condition, such as social anxiety disorder, or a somatic condition, such as chronic pain. Two reviewers independently rated study quality. Twenty-five studies, targeting 11 different disorders, were included in the review. Study quality and presentation of treatment variables, such as therapist time and treatment adherence, varied largely. Twenty-four studies (N=1882) were included in the meta-analysis and ICBT yielded moderate between group effect sizes when compared with waitlist, g=0.62, 95% CI [0.41, 0.84]. The results suggest that CBT for psychiatric and somatic conditions in children and adolescents can be successfully adapted to an internet-delivered format. PMID- 27668989 TI - The pattern ERG in chicks - Stimulus dependence and optic nerve section. AB - The chick is widely used in studies of eye growth regulation and myopia. The aim of this study was to explore the utility of pattern (p)ERG as a tool to assess retinal function in such studies. Effects of optical defocus and diffusing blur, manipulations used to alter eye growth experimentally, were evaluated. PERGs were recorded from White-Leghorn chickens, using a checkerboard pattern, including 8 spatial frequencies (0.05-2.2c/d SF), 13 contrast levels (1-100%), and 8 temporal reversal frequencies (0.5-20Hz). The acute effects of defocus and diffusing blur were examined. Flash- and pERGs were also recorded from chicks that underwent monocular optic nerve section (ONS), to explore the contribution of retinal ganglion cells (RGCs). Measurements were made up to 6weeks post-ONS, complemented with SD-OCT imaging. In normal chicks, the response to 1Hz, 100% contrast stimuli showed positive- and negative-going waveforms at 43ms (P1) and 75ms (N95), respectively, with 0.06-0.1c/d SF eliciting the largest P1 amplitudes of 21.9+/ 2.5MUV. Contrast levels above 5% yielded measurable P1 responses. Responses were transient and monophasic for 0.5-5Hzreversal rates, with higher temporal frequencies yielding steady state responses. Defocus and diffusing blur decreased pERG amplitude across all SFs. pERG responses remained normal after ONS, despite the loss of RGCs. In conclusion, chicks show robust pERG responses, which are attenuated by defocus and diffusing blur. The pERG response is not affected by ONS, suggesting that RGCs do not contribute to the chick pERG. PMID- 27668991 TI - Characterization of key organic compounds affecting sludge dewaterability during ultrasonication and acidification treatments. AB - This study investigated the mechanism and effects of ultrasonic pretreatment followed by acidification on sludge dewaterability through looking at the changes of extracellular polymeric substances (EPS) content, composition and stratification. The results suggested sludge filterability was closely correlated with quantity of protein (R = 0.94, p < 0.01) and polysaccharide (R = 0.97, p < 0.01) present in loosely bound EPS rather than in soluble and tightly bound EPS. The fractions of polymers, especially tryptophan-like proteins and microbial by product like material at molecular weight of 106-5 * 107 Da, were the key compounds related to sludge filterability. Ultrasonication may increase biopolymers concentrations that in turn deteriorate sludge filterability as evidenced at high ultrasonic power conditions. However, the subsequent acidification can reduce the concentrations of these organic compounds, reduce negative zeta potential, and increase floc size, thus increase sludge filterability. Combined ultrasonic-acid pretreamtent was more effective than the acidification treatment alone in reducing the concentrations of macromolecular compounds that may deteriorate sludge filterability. PMID- 27668992 TI - Strongly enhanced Fenton degradation of organic pollutants by cysteine: An aliphatic amino acid accelerator outweighs hydroquinone analogues. AB - Quinone-hydroquinone analogues have been proven to be efficient promoters of Fenton reactions by accelerating the Fe(III)/Fe(II) redox cycle along with self destruction. However, so far there is little information on non-quinone hydroquinone cocatalyst for Fenton reactions. This study found that cysteine, a common aliphatic amino acid, can strongly enhance Fenton degradation of organic pollutants by accelerating Fe(III)/Fe(II) redox cycle, as quinone-hydroquinone analogues do. Further, cysteine is superior to quinone-hydroquinone analogues in catalytic activity, H2O2 utilization and atmospheric limits. The cocatalysis mechanism based on the cycle of cysteine/cystine was proposed. PMID- 27668993 TI - Life cycle assessment and costing of urine source separation: Focus on nonsteroidal anti-inflammatory drug removal. AB - Urine source separation has the potential to reduce pharmaceutical loading to the environment, while enhancing nutrient recovery. The focus of this life cycle assessment (LCA) was to evaluate the environmental impacts and economic costs to manage nonsteroidal anti-inflammatory drugs (NSAIDs) (i.e., diclofenac, ibuprofen, ketoprofen and naproxen) and nutrients in human urine. Urine source separation was compared with centralized wastewater treatment (WWT) (biological or upgraded with ozonation). The current treatment method (i.e., centralized biological WWT) was compared with hypothetical treatment scenarios (i.e., centralized biological WWT upgraded with ozonation, and urine source separation). Alternative urine source separation scenarios included varying collection and handling methods (i.e., collection by vacuum truck, vacuum sewer, or decentralized treatment), pharmaceuticals removal by ion-exchange, and struvite precipitation. Urine source separation scenarios had 90% lower environmental impact (based on the TRACI impact assessment method) compared with the centralized wastewater scenarios due to reduced potable water production for flush water, reduced electricity use at the wastewater treatment plant, and nutrient offsets from struvite precipitation. Despite the greatest reduction of pharmaceutical toxicity, centralized treatment upgraded with ozone had the greatest ecotoxicity impacts due to ozonation operation and infrastructure. Among urine source separation scenarios, decentralized treatment of urine and centralized treatment of urine collected by vacuum truck had negligible cost differences compared with centralized wastewater treatment. Centralized treatment of urine collected by vacuum sewer and centralized treatment with ozone cost 30% more compared with conventional wastewater treatment. PMID- 27668994 TI - Mineralizing urban net-zero water treatment: Phase II field results and design recommendations. AB - Net-zero water (NZW) systems, or water management systems achieving high recycling rates and low residuals generation so as to avoid water import and export, can also conserve energy used to heat and convey water, while economically restoring local eco-hydrology. However, design and operating experience are extremely limited. The objective of this paper is to present the results of the second phase of operation of an advanced oxidation-based NZW pilot system designed, constructed, and operated for a period of two years, serving an occupied four-person apartment. System water was monitored, either continuously or thrice daily, for routine water quality parameters, minerals, and MicroTox(r) in-vitro toxicity, and intermittently for somatic and male-specific coliphage, adenovirus, Cryptosporidium, Giardia, emerging organic constituents (non quantitative), and the Florida drinking water standards. All 115 drinking water standards with the exception of bromate were met in this phase. Neither virus nor protozoa were detected in the treated water, with the exception of measurement of adenovirus genome copies attributed to accumulation of inactive genetic material in hydraulic dead zones. Chemical oxygen demand was mineralized to <0.7 mg/L, and all but six of 1006 emerging organic constituents analyzed were either undetected or removed >90% in treatment. Total dissolved solids were maintained at ~500 mg/L at steady state, partially through aerated aluminum electrocoagulation. Bromate accumulation is projected to be controlled by aluminum electrocoagulation with separate disposal of backwash water. Further development of such systems and their automated/remote process control systems is recommended. PMID- 27668995 TI - Community structure, population dynamics and diversity of fungi in a full-scale membrane bioreactor (MBR) for urban wastewater treatment. AB - Community structure, population dynamics and diversity of fungi were monitored in a full-scale membrane bioreactor (MBR) operated throughout four experimental phases (Summer 2009, Autumn 2009, Summer 2010 and Winter, 2012) under different conditions, using the 18S-rRNA gene and the intergenic transcribed spacer (ITS2 region) as molecular markers, and a combination of temperature-gradient gel electrophoresis and 454-pyrosequencing. Both total and metabolically-active fungal populations were fingerprinted, by amplification of molecular markers from community DNA and retrotranscribed RNA, respectively. Fingerprinting and 454 pyrosequencing evidenced that the MBR sheltered a dynamic fungal community composed of a low number of species, in accordance with the knowledge of fungal diversity in freshwater environments, and displaying a medium-high level of functional organization with few numerically dominant phylotypes. Population shifts were experienced in strong correlation with the changes of environmental variables and operation parameters, with pH contributing the highest level of explanation. Phylotypes assigned to nine different fungal Phyla were detected, although the community was mainly composed of Ascomycota, Basidiomycota and Chytridiomycota/Blastocladiomycota. Prevailing fungal phylotypes were affiliated to Saccharomycetes and Chytridiomycetes/Blastocladiomycetes, which displayed antagonistic trends in their relative abundance throughout the experimental period. Fungi identified in the activated sludge were closely related to genera of relevance for the degradation of organic matter and trace-organic contaminants, as well as genera of dimorphic fungi potentially able to produce plant operational issues such as foaming or biofouling. Phylotypes closely related to genera of human and plant pathogenic fungi were also detected. PMID- 27668990 TI - Neural mechanisms of information storage in visual short-term memory. AB - The capacity to briefly memorize fleeting sensory information supports visual search and behavioral interactions with relevant stimuli in the environment. Traditionally, studies investigating the neural basis of visual short term memory (STM) have focused on the role of prefrontal cortex (PFC) in exerting executive control over what information is stored and how it is adaptively used to guide behavior. However, the neural substrates that support the actual storage of content-specific information in STM are more controversial, with some attributing this function to PFC and others to the specialized areas of early visual cortex that initially encode incoming sensory stimuli. In contrast to these traditional views, I will review evidence suggesting that content-specific information can be flexibly maintained in areas across the cortical hierarchy ranging from early visual cortex to PFC. While the factors that determine exactly where content specific information is represented are not yet entirely clear, recognizing the importance of task-demands and better understanding the operation of non-spiking neural codes may help to constrain new theories about how memories are maintained at different resolutions, across different timescales, and in the presence of distracting information. PMID- 27668996 TI - Azo dye decolorization in an up-flow bioelectrochemical reactor with domestic wastewater as a cost-effective yet highly efficient electron donor source. AB - A major challenge of employing bioelectrochemical system (BES) for reductively degrading recalcitrant contaminants in industrial wastewater is lacking sufficient electron donors. In this work, domestic wastewater (DW) was demonstrated to efficiently drive BES for implementing the decolorization of azo dye, acid orange 7 (AO7). Side benefit was the simultaneous treatment of DW. Decolorization efficiency in BES fed with DW (RDW) was found to be comparable with that either fed with glucose (RGlu) or acetate (RAc). Much lower reductant usage ratio was observed in RDW. As a result, when the ratio of electron donors to azo dye decreased to 4.4 mol COD mol-1 AO7, DE of RDW kept over 90% while DEs of RAc and RGlu were significantly dropped due to the insufficient electrons donation. Besides serving as electron donor, DW was proved to also provide some conductivity and buffer capacity. Accordingly, DE of RDW was less deteriorated when fully removing the external buffer slats. This study comprehensively revealed the feasibility and superiority of DW as a cost-effective electron donor source in BES and brings this technology closer to the practice. PMID- 27668998 TI - Evaluation and comparison of current biopsy needle localization and tracking methods using 3D ultrasound. AB - This article compares four different biopsy needle localization algorithms in both 3D and 4D situations to evaluate their accuracy and execution time. The localization algorithms were: Principle component analysis (PCA), random Hough transform (RHT), parallel integral projection (PIP) and ROI-RK (ROI based RANSAC and Kalman filter). To enhance the contrast of the biopsy needle and background tissue, a line filtering pre-processing step was implemented. To make the PCA, RHT and PIP algorithms comparable with the ROI-RK method, a region of interest (ROI) strategy was added. Simulated and ex-vivo data were used to evaluate the performance of the different biopsy needle localization algorithms. The resolutions of the sectorial and cylindrical volumes were 0.3mm*0.4mm*0.6mmand0.1mm*0.1mm*0.2mm (axial*lateral*azimuthal) respectively. In so far as the simulation and experimental results show, the ROI-RK method successfully located and tracked the biopsy needle in both 3D and 4D situations. The tip localization error was within 1.5mm and the axis accuracy was within 1.6mm. To the best of our knowledge, considering both localization accuracy and execution time, the ROI-RK was the most stable and time-saving method. Normally, accuracy comes at the expense of time. However, the ROI-RK method was able to locate the biopsy needle with high accuracy in real time, which makes it a promising method for clinical applications. PMID- 27668997 TI - Rhesus rotavirus VP6 regulates ERK-dependent calcium influx in cholangiocytes. AB - The Rhesus rotavirus (RRV) induced murine model of biliary atresia (BA) is a useful tool in studying the pathogenesis of this neonatal biliary obstructive disease. In this model, the mitogen associated protein kinase pathway is involved in RRV infection of biliary epithelial cells (cholangiocytes). We hypothesized that extracellular signal-related kinase (ERK) phosphorylation is integral to calcium influx, allowing for viral replication within the cholangiocyte. Utilizing ERK and calcium inhibitors in immortalized cholangiocytes and BALB/c pups, we determined that ERK inhibition resulted in reduced viral yield and subsequent decreased symptomatology in mice. In vitro, the RRV VP6 protein induced ERK phosphorylation, leading to cellular calcium influx. Pre-treatment with an ERK inhibitor or Verapamil resulted in lower viral yields. We conclude that the pathogenesis of RRV-induced murine BA is dependent on the VP6 protein causing ERK phosphorylation and triggering calcium influx allowing replication in cholangiocytes. PMID- 27668999 TI - A pre-trained convolutional neural network based method for thyroid nodule diagnosis. AB - In ultrasound images, most thyroid nodules are in heterogeneous appearances with various internal components and also have vague boundaries, so it is difficult for physicians to discriminate malignant thyroid nodules from benign ones. In this study, we propose a hybrid method for thyroid nodule diagnosis, which is a fusion of two pre-trained convolutional neural networks (CNNs) with different convolutional layers and fully-connected layers. Firstly, the two networks pre trained with ImageNet database are separately trained. Secondly, we fuse feature maps learned by trained convolutional filters, pooling and normalization operations of the two CNNs. Finally, with the fused feature maps, a softmax classifier is used to diagnose thyroid nodules. The proposed method is validated on 15,000 ultrasound images collected from two local hospitals. Experiment results show that the proposed CNN based methods can accurately and effectively diagnose thyroid nodules. In addition, the fusion of the two CNN based models lead to significant performance improvement, with an accuracy of 83.02%+/-0.72%. These demonstrate the potential clinical applications of this method. PMID- 27669002 TI - Editorial Statement. PMID- 27669000 TI - Investigating Differences Between Drugs Used in the Australian Night-Time Economy: Demographics, Substance Use, and Harm. AB - BACKGROUND: Understanding the characteristics of drug users in the night-time economy (NTE), and whether particular drugs are associated with risky practices and experience of harm, is necessary to inform targeted policy responses in this context. OBJECTIVES: To investigate the correlates of drugs used in the Australian NTE relating to demographics, alcohol use, and experience of harm. METHODS: Patrons were interviewed in the NTE of five Australian cities in 2012 2013 (n = 7,028; 61.9% male, median age 22 years). A custom designed survey gathered demographic data, alcohol, and substance use on the current night, and experience of harm in/around licensed venues in the past 3 months. Multivariate logistic regression analyses examined the correlates of drug use. RESULTS: Ecstasy was most commonly reported (4.0%), followed by cannabis (2.9%), methamphetamine (2.6%), and cocaine (1.6%). Ecstasy users were more likely to be younger and report energy drink consumption. Cannabis users were more likely to be male, and to have been involved in intoxication-related accidents/injuries and sexual aggression in/around licensed venues in the past 3 months. Methamphetamine users were more likely to have been interviewed later, and to have engaged in pre drinking. Cocaine users were more likely to be male, aged 21 years or more, have a blood alcohol concentration of greater than 0.10%, and to have been involved in intoxication-related accidents/injuries in the past three months. Conclusions/Importance: We identified significant differences between types of drug users and the harms they experience, underscoring the need to develop innovative harm reduction policies in the NTE rather than blanket population based approaches. PMID- 27669001 TI - Editorial Notes. PMID- 27669003 TI - Two Cases of Retinoblastoma Invading the Optic Nerve Sheath. AB - The authors report two cases of retinoblastoma with extension along the optic nerve sheath with negative surgical margins, a pattern not considered in current classifications but suggesting a high risk of metastasis. Both patients were treated with adjuvant chemotherapy alone and remain free of extraocular disease 15 and 22 months later. [J Pediatr Ophthalmol Strabismus. 2016;53:e51-e53.]. PMID- 27669004 TI - Development and Characterization of Genic SSR Markers from Indian Mulberry Transcriptome and Their Transferability to Related Species of Moraceae. AB - Improving mulberry leaf production with enhanced leaf quality holds the key to sustain the ever increasing demand for silk. Adoption of modern genomic approaches for crop improvement is severely constrained by the lack of sufficient molecular markers in mulberry. Here, we report development and validation of 206 EST derived SSR markers using transcriptome data generated from leaf tissue of a drought tolerant mulberry genotype, Dudia white. Analysis of transcriptome data containing 10169 EST sequences, revealed 1469 sequences with microsatellite repeat motifs. We designed a total of 264 primers to the most appropriate repeat regions, of which 206 were locus specific. These markers were validated with 25 diverse mulberry accessions and their transferability to closely related species belonging to family Moraceae was examined. Of these markers, 189 revealed polymorphism with up to 8 allelic forms across mulberry species, genotypes and varieties with a mean of 3.5 alleles per locus. The markers also revealed higher polymorphic information content of 0.824 among the accessions. These markers effectively segregated the species and genotypes and hence, can be used for both diversity analysis and in breeding applications. Around 40% of these markers were transferable to other closely related species. Along with the other genic and genomic markers, we report a set of over 750 co-dominant markers. Using these markers we constructed the first genetic linkage map of mulberry exclusively with co-dominant markers. PMID- 27669005 TI - Design of Distributed Engine Control Systems with Uncertain Delay. AB - Future gas turbine engine control systems will be based on distributed architecture, in which, the sensors and actuators will be connected to the controllers via a communication network. The performance of the distributed engine control (DEC) is dependent on the network performance. This study introduces a distributed control system architecture based on a networked cascade control system (NCCS). Typical turboshaft engine-distributed controllers are designed based on the NCCS framework with a Hinfinity output feedback under network-induced time delays and uncertain disturbances. The sufficient conditions for robust stability are derived via the Lyapunov stability theory and linear matrix inequality approach. Both numerical and hardware-in-loop simulations illustrate the effectiveness of the presented method. PMID- 27669006 TI - Albuminuria Is Associated with Endothelial Dysfunction and Elevated Plasma Endothelin-1 in Sickle Cell Anemia. AB - BACKGROUND: The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin). METHODS: Spot urine measurements for albumin-creatinine ratio (UACR) and 24-hour urine protein were obtained. Endothelial function was assessed using brachial artery ultrasound with measurements of flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NTMD) and hyperemic velocity. RESULTS: Twenty three subjects with varying degrees of albuminuria were evaluated. UACR was significantly correlated with FMD (rho = -0.45, p = 0.031). In univariate analysis, UACR was correlated with VEGF (rho = -0.49; 95% CI: -0.75 --0.1, p = 0.015), plasma hemoglobin (rho = 0.50; 95% CI: 0.11-0.75, p = 0.013) and ET-1 (rho = 0.40; 95% CI: -0.03-0.69, p = 0.06). Multivariable analysis showed significant associations of ET-1 (estimate: 455.1 [SE: 198.3], p = 0.02), VEGF (estimate: -1.1 [SE: 0.53], p = 0.04) and sFLT-1 (estimate: -1.14 [SE: 0.49], p = 0.02) with UACR. Only ET-1 (estimate: -8.03 [SE: 3.87], p = 0.04) was significantly associated with FMD in multivariable analyses. Finally, UACR was correlated with both 24-hour urine protein (rho = 0.90, p < 0.0001) and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection (rho = 0.97, p < 0.0001). CONCLUSION: This study provides more definitive evidence for the association of albuminuria with endothelial dysfunction in SCD. Elevated circulating levels of ET-1 may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction. PMID- 27669007 TI - Spatial Heterogeneity of Gut Microbial Composition along the Gastrointestinal Tract in Natural Populations of House Mice. AB - There is a growing appreciation of the role of gut microbial communities in host biology. However, the nature of variation in microbial communities among different segments of the gastrointestinal (GI) tract is not well understood. Here, we describe microbial communities from ten different segments of the GI tract (mouth, esophagus, stomach, duodenum, ileum, proximal cecum, distal cecum, colon, rectum, and feces) in wild house mice using 16S rRNA gene amplicon sequencing. We also measured carbon and nitrogen stable isotopic ratios from hair samples of individual mice as a proxy for diet. We identified factors that may explain differences in microbial composition among gut segments, and we tested for differences among individual mice in the composition of the microbiota. Consistent with previous studies, the lower GI tract was characterized by a greater relative abundance of anaerobic bacteria and greater microbial diversity relative to the upper GI tract. The upper and lower GI tracts also differed in the relative abundances of predicted microbial gene functions, including those involved in metabolic pathways. However, when the upper and lower GI tracts were considered separately, gut microbial composition was associated with individual mice. Finally, microbial communities derived from fecal samples were similar to those derived from the lower GI tract of their respective hosts, supporting the utility of fecal sampling for studying the gut microbiota of mice. These results show that while there is substantial heterogeneity among segments of the GI tract, individual hosts play a significant role in structuring microbial communities within particular segments of the GI tract. PMID- 27669009 TI - SURVEILLANCE FOR VIRAL AND PARASITIC PATHOGENS IN A VULNERABLE AFRICAN LION (PANTHERA LEO) POPULATION IN THE NORTHERN TULI GAME RESERVE, BOTSWANA. AB - African lion ( Panthera leo ) numbers are decreasing rapidly and populations are becoming smaller and more fragmented. Infectious diseases are one of numerous issues threatening free-ranging lion populations, and low-density populations are particularly at risk. We collected data on the prevalence and diversity of viral and parasitic pathogens in a small lion population in eastern Botswana. During 2012 and 2014, blood samples were collected from 59% (n=13) of the adult-subadult lions in the Northern Tuli Game Reserve in eastern Botswana. One lion had antibodies to feline panleukopenia virus, two had antibodies to canine distemper virus, and two had feline calicivirus antibodies. Ten of the 13 had antibodies to feline immunodeficiency virus and 11 had feline herpesvirus antibodies. All lions were negative for antibodies to feline coronavirus. Blood samples from all lions were negative for Trypanosoma, Anaplasma, Theileria, and Ehrlichia spp. by molecular testing; however, all lions were positive for Babesia spp. by reverse line blot hybridization assay. Sequencing of amplicons from four lions revealed four groups of Babesia spp. including several genetic variants of Babesia felis , Babesia lengau, and Babesia canis and a group of novel Babesia sequences which were only 96% similar to other Babesia spp. Six lions were infested with four species of ticks (Rhipicentor nuttalli, Rhipicephalus simus, Rhipicephalus sulcatus, and Rhipicephalus appendiculatus). These data provide the first health assessment of this population and can be used to identify management and conservation strategies to decrease the impact of pathogens on this population. This is particularly important as there is an initiative to incorporate this population into a larger metapopulation of lions from adjacent South Africa and Zimbabwe. PMID- 27669010 TI - Neospora caninum in Axis Deer ( Axis axis ) and Fallow Deer ( Dama dama ) in Northern Mexico. AB - Serum samples from 18 axis deer ( Axis axis ) and 19 fallow deer ( Dama dama ) were analyzed with an enzyme-linked immunosorbent assay for Neospora caninum antibodies. Two axis (11%) and two fallow deer (11%) were positive for N. caninum antibodies. PMID- 27669008 TI - Normal Hematopoietic Progenitor Subsets Have Distinct Reactive Oxygen Species, BCL2 and Cell-Cycle Profiles That Are Decoupled from Maturation in Acute Myeloid Leukemia. AB - In acute myeloid leukemia (AML) quiescence and low oxidative state, linked to BCL2 mitochondrial regulation, endow leukemic stem cells (LSC) with treatment resistance. LSC in CD34+ and more mature CD34- AML have heterogeneous immunophenotypes overlapping with normal stem/progenitor cells (SPC) but may be differentiated by functional markers. We therefore investigated the oxidative/reactive oxygen species (ROS) profile, its relationship with cell cycle/BCL2 for normal SPC, and whether altered in AML and myelodysplasia (MDS). In control BM (n = 24), ROS levels were highest in granulocyte-macrophage progenitors (GMP) and CD34- myeloid precursors but megakaryocyte-erythroid progenitors had equivalent levels to CD34+CD38low immature-SPC although they were ki67high. BCL2 upregulation was specific to GMPs. This profile was also observed for CD34+SPC in MDS-without-excess-blasts (MDS-noEB, n = 12). Erythroid CD34- precursors were, however, abnormally ROS-high in MDS-noEB, potentially linking oxidative stress to cell loss. In pre-treatment AML (n = 93) and MDS-with-excess blasts (MDS-RAEB) (n = 14), immunophenotypic mature-SPC had similar ROS levels to co-existing immature-SPC. However ROS levels varied between AMLs; Flt3ITD+/NPM1wild-type CD34+SPC had higher ROS than NPM1mutated CD34+ or CD34- SPC. An aberrant ki67lowBCL2high immunophenotype was observed in CD34+AML (most prominent in Flt3ITD AMLs) but also in CD34- AMLs and MDS-RAEB, suggesting a shared redox/pro-survival adaptation. Some patients had BCL2 overexpression in CD34+ ROS-high as well as ROS-low fractions which may be indicative of poor early response to standard chemotherapy. Thus normal SPC subsets have distinct ROS, cell-cycle, BCL2 profiles that in AML /MDS-RAEB are decoupled from maturation. The combined profile of these functional properties in AML subpopulations may be relevant to differential treatment resistance. PMID- 27669011 TI - Comparison of Two Bacterial Transport Media for Culture of Tonsilar Swabs from Bighorn Sheep ( Ovis canadensis ) and Mountain Goats ( Oreamnos americanus ). AB - Duplicate tonsilar swabs were collected from 77 bighorn sheep ( Ovis canadensis ) and 19 mountain goats ( Oreamnos americanus ) in Utah. Swabs were refrigerated in bacterial transport medium or frozen in cryopreservation medium prior to bacteriologic culture. The cryopreservation medium yielded comparable or superior bacterial growth while permitting more flexibility in specimen shipment to the laboratory. PMID- 27669012 TI - SARCOPTIC MANGE IN ENDANGERED KIT FOXES (VULPES MACROTIS MUTICA): CASE HISTORIES, DIAGNOSES, AND IMPLICATIONS FOR CONSERVATION. AB - The San Joaquin kit fox ( Vulpes macrotis mutica) is a federally endangered small carnivore whose distribution is limited to the San Joaquin Valley in central California. Population decline is due to profound habitat loss, and conservation of all remaining populations is critical. A robust urban population occurs in the city of Bakersfield. In spring of 2013, putative cases of mange were reported in this population. Mites from affected animals were confirmed to be Sarcoptes scabiei morphologically and by DNA sequencing. By the end of 2014, 15 cases of kit foxes with mange had been confirmed. As with other species, sarcoptic mange in kit foxes is characterized by intense pruritus and dermatitis, caused by mites burrowing into the epidermal layers, as well as alopecia, hyperkeratosis, and encrustations, secondary bacterial infections, and finally extreme morbidity and death. Of the 15 cases, six foxes were found dead, six were captured but died during attempted rehabilitation, and three were successfully treated. We have no evidence that untreated kit foxes can recover from mange. Sarcoptic mange constitutes a significant threat to the Bakersfield kit fox population and could pose an even greater threat to this imperiled species if it spreads to populations in nearby natural lands. PMID- 27669013 TI - Non-Invasive Detection of Protein Content in Several Types of Plant Feed Materials Using a Hybrid Near Infrared Spectroscopy Model. AB - Near-infrared spectroscopy combined with chemometrics was applied to construct a hybrid model for the non-invasive detection of protein content in different types of plant feed materials. In total, 829 samples of plant feed materials, which included corn distillers' dried grains with solubles (DDGS), corn germ meal, corn gluten meal, distillers' dried grains (DDG) and rapeseed meal, were collected from markets in China. Based on the different preprocessed spectral data, specific models for each type of plant feed material and a hybrid model for all the materials were built. Performances of specific model and hybrid model constructed with full spectrum (full spectrum model) and selected wavenumbers with VIP (variable importance in the projection) scores value bigger than 1.00 (VIP scores model) were also compared. The best spectral preprocessing method for this study was found to be the standard normal variate transformation combined with the first derivative. For both full spectrum and VIP scores model, the prediction performance of the hybrid model was slightly worse than those of the specific models but was nevertheless satisfactory. Moreover, the VIP scores model obtained generally better performances than corresponding full spectrum model. Wavenumbers around 4500 cm-1, 4664 cm-1 and 4836 cm-1 were found to be the key wavenumbers in modeling protein content in these plant feed materials. The values for the root mean square error of prediction (RMSEP) and the relative prediction deviation (RPD) obtained with the VIP scores hybrid model were 1.05% and 2.53 for corn DDGS, 0.98% and 4.17 for corn germ meal, 0.75% and 6.99 for corn gluten meal, 1.54% and 4.59 for DDG, and 0.90% and 3.33 for rapeseed meal, respectively. The results of this study demonstrate that the protein content in several types of plant feed materials can be determined using a hybrid near-infrared spectroscopy model. And VIP scores method can be used to improve the general predictability of hybrid model. PMID- 27669014 TI - Taxes on Sugar-Sweetened Beverages to Reduce Overweight and Obesity in Middle Income Countries: A Systematic Review. AB - BACKGROUND: The consumption of sugar-sweetened beverages (SSBs), which can lead to weight gain, is rising in middle-income countries (MICs). Taxing SSBs may help address this challenge. Systematic reviews focused on high-income countries indicate that taxing SSBs may reduce SSB consumption. Responsiveness to price changes may differ in MICs, where governments are considering the tax. To help inform their policy decisions, this review compiles evidence from MICs, assessing post-tax price increases (objective 1), changes in demand for SSBs and other products, overall and by socio-economic groups (objective 2), and effects on overweight and obesity prevalence (objective 3). METHODS AND FINDINGS: We conducted a systematic review on the effectiveness of SSB taxation in MICs (1990 2016) and identified nine studies from Brazil, Ecuador, India, Mexico, Peru, and South Africa. Estimates for own-price elasticity ranged from -0.6 to -1.2, and decreases in SSB consumption ranged from 5 to 39 kilojoules per person per day given a 10% increase in SSB prices. The review found that milk is a likely substitute, and foods prepared away from home, snacks, and candy are likely complements to SSBs. A quasi-experimental study and two modeling studies also found a negative relationship between SSB prices and obesity outcomes after accounting for substitution effects. Estimates are consistent despite variation in baseline obesity prevalence and per person per day consumption of SSBs across countries studied. CONCLUSIONS: The review indicates that taxing SSBs will increase the prices of SSBs, especially sugary soda, in markets with few producers. Taxing SSBs will also reduce net energy intake by enough to prevent further growth in obesity prevalence, but not to reduce population weight permanently. Additional research using better survey data and stronger study designs is needed to ascertain the long-term effectiveness of an SSB tax on obesity prevalence in MICs. PMID- 27669016 TI - Hydroxylation of multi-walled carbon nanotubes: Enhanced biocompatibility through reduction of oxidative stress initiated cell membrane damage, cell cycle arrestment and extrinsic apoptotic pathway. AB - Modification of CNTs with hydroxyl group promotes their applications in biomedical area. However, the impact of hydroxylation on their biocompatibility is far from being completely understood. In this study, we carried out a comprehensive evaluation of hydroxylated multi-walled carbon nanotubes (MWCNTs OH) on the human normal liver L02 cell line, and compared it with that of pristine multi-walled carbon nanotubes (p-MWCNTs). Results demonstrated that compared with p-MWCNTs, MWCNTs-OH induced significantly lower oxidative stress as indicated by the level of intracellular antioxidant glutathione (GSH), subsequently lead to less cell membrane damage as demonstrated by lactate dehydrogenase (LDH) leakage assay, and showed slightly decreased arrestment of cell cycle distribution at G0/G1. More interestingly, MWCNTs-OH exhibited significantly lower tendency to activate caspase-8, a key molecule involved in the extrinsic apoptotic pathway. All these in vitro results demonstrated that hydroxylation of MWCNTs enhanced their biocompatibility compare with p-MWCNTs. PMID- 27669015 TI - Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation. AB - BACKGROUND: Maximal exercise capacity after heart transplantion (HTx) is reduced to the 50-70% level of healthy controls when assessed by cardiopulmonary exercise testing (CPET) despite of normal left ventricular function of the donor heart. This study investigates the role of donor heart beta1 and beta2- adrenergic receptor (AR) polymorphisms for maximal exercise capacity after orthotopic HTx. METHODS: CPET measured peak VO2 as outcome parameter for maximal exercise in HTx recipients >=9 months and <=4 years post-transplant (n = 41; mean peak VO2: 57+/ 15% of predicted value). Donor hearts were genotyped for polymorphisms of the beta1-AR (Ser49Gly, Arg389Gly) and the beta2-AR (Arg16Gly, Gln27Glu). Circumferential shortening of the left ventricle was measured using magnetic resonance based CSPAMM tagging. RESULTS: Peak VO2 was higher in donor hearts expressing the beta1-Ser49Ser alleles when compared with beta1-Gly49 carriers (60+/-15% vs. 47+/-10% of the predicted value; p = 0.015), and by trend in cardiac allografts with the beta1-AR Gly389Gly vs. beta1-Arg389 (61+/-15% vs. 54+/-14%, p = 0.093). Peak VO2 was highest for the haplotype Ser49Ser-Gly389, and decreased progressively for Ser49Ser-Arg389Arg > 49Gly-389Gly > 49Gly-Arg389Arg (adjusted R2 = 0.56, p = 0.003). Peak VO2 was not different for the tested beta2 AR polymorphisms. Independent predictors of peak VO2 (adjusted R2 = 0.55) were beta1-AR Ser49Gly SNP (p = 0.005), heart rate increase (p = 0.016), and peak systolic blood pressure (p = 0.031). Left ventricular (LV) motion kinetics as measured by cardiac MRI CSPAMM tagging at rest was not different between carriers and non-carriers of the beta1-AR Gly49allele. CONCLUSION: Similar LV cardiac motion kinetics at rest in donor hearts carrying either beta1-AR Gly49 or beta1 Ser49Ser variant suggests exercise-induced desensitization and down-regulation of the beta1-AR Gly49 variant as relevant pathomechanism for reduced peak VO2 in beta1-AR Gly49 carriers. PMID- 27669017 TI - High-dose inactivated influenza vaccine is associated with cost savings and better outcomes compared to standard-dose inactivated influenza vaccine in Canadian seniors. AB - Seasonal influenza infects approximately 10-20% of Canadians each year, causing an estimated 12,200 hospitalizations and 3,500 deaths annually, mostly occurring in adults >=65 years old (seniors). A 32,000-participant, randomized controlled clinical trial (FIM12; Clinicaltrials.gov NCT01427309) showed that high-dose inactivated influenza vaccine (IIV-HD) is superior to standard-dose vaccine (SD) in preventing laboratory-confirmed influenza illness in seniors. In this study, we performed a cost-utility analysis (CUA) of IIV-HD versus SD in FIM12 participants from a Canadian perspective. Healthcare resource utilization data collected in FIM12 included: medications, non-routine/urgent care and emergency room visits, and hospitalizations. Unit costs were applied using standard Canadian cost sources to estimate the mean direct medical and societal costs associated with each vaccine (2014 CAD). Clinical illness data from the trial were mapped to quality-of-life data from the literature to estimate differences in effectiveness between vaccines. Time horizon was one influenza season, however, quality-adjusted life-years (QALYs) lost due to death during the study were captured over a lifetime. A probabilistic sensitivity analysis (PSA) was also performed. Average per-participant medical costs were $47 lower and societal costs $60 lower in the IIV-HD arm. Hospitalizations contributed 91% of the total cost and were less frequent in the IIV-HD arm. IIV-HD provided a gain in QALYs and, due to cost savings, dominated SD in the CUA. The PSA indicated that IIV-HD is 89% likely to be cost saving. In Canada, IIV-HD is expected to be a less costly and more effective alternative to SD, driven by a reduction in hospitalizations. PMID- 27669018 TI - Dynamic Control of Synchronous Activity in Networks of Spiking Neurons. AB - Oscillatory brain activity is believed to play a central role in neural coding. Accumulating evidence shows that features of these oscillations are highly dynamic: power, frequency and phase fluctuate alongside changes in behavior and task demands. The role and mechanism supporting this variability is however poorly understood. We here analyze a network of recurrently connected spiking neurons with time delay displaying stable synchronous dynamics. Using mean-field and stability analyses, we investigate the influence of dynamic inputs on the frequency of firing rate oscillations. We show that afferent noise, mimicking inputs to the neurons, causes smoothing of the system's response function, displacing equilibria and altering the stability of oscillatory states. Our analysis further shows that these noise-induced changes cause a shift of the peak frequency of synchronous oscillations that scales with input intensity, leading the network towards critical states. We lastly discuss the extension of these principles to periodic stimulation, in which externally applied driving signals can trigger analogous phenomena. Our results reveal one possible mechanism involved in shaping oscillatory activity in the brain and associated control principles. PMID- 27669019 TI - Effect of participants' static stretching knowledge or deception on the responses to prolonged stretching. AB - Much of the static stretching (SS) literature reports performance impairments with prolonged SS. However, it has been acknowledged that a limitation of these studies is participants' knowledge or bias. Since many participants have knowledge of the literature, their performance may be subconsciously influenced by expectations. Hence, the objective of this study was to examine the effect of stretching knowledge or deception on subsequent force output following SS. Two groups of male participants who were either aware (BIASED: 14) or unaware (DECEPTION: 14) of the SS literature participated. Unaware participants were misinformed that SS increases force production. Testing involved maximal voluntary isometric contractions (MVC) of the quadriceps and hamstrings at pre-, post-, and 5 min post-intervention (three 30-s passive hamstring stretches to the point of discomfort with 30-s rest intervals) or control. While the DECEPTION group displayed impaired knee flexion force (p = 0.04; 3.6% and 10.4%) following hamstrings SS, there was no significant impairment with the BIASED (-1.1% and +0.9%) group. Both groups exhibited hamstrings F200 (force produced in the first 200 ms) impairments following SS. Whereas BIASED participants exhibited an overall decrease (p < 0.05; 1.8% and 4.2%) in knee extension MVC, DECEPTION participants showed (p = 0.005; 8.8% and 5.1%) force increases. The quadriceps F200 was not significantly affected with the BIASED group but overall there were 4.5% and 8.7% F200 impairments at 1 and 5 min post-intervention (p = 0.05) with the DECEPTION group. Thus while deception resulted in enhanced quadriceps muscle force output, there was no knowledge or deception advantage when stretching the hamstrings. PMID- 27669020 TI - Wild blueberry consumption attenuates local inflammation in the perivascular adipose tissue of obese Zucker rats. AB - Perivascular adipose tissue (PVAT) has been shown to play important roles in regulating vascular tone and linking local and systemic vascular inflammation. We examined the impact of PVAT on phenylephrine-mediated vasoconstriction in the aorta of obese Zucker rats (OZR) and their lean littermates (LZR) by comparing aortic rings with or without PVAT. Subsequently we placed OZR and LZR on a control (C) or an 8% wild blueberry (WB) diet and evaluated the effect of WB consumption on such response. PVAT-released adipokine concentrations were also measured as a function of WB diet. Maximal constrictor force (Fmax) in aortic rings without PVAT was significantly lower in OZR-C compared with LZR-C (0.41 +/- 0.05 and 0.71 +/- 0.06 g, respectively). Following WB diet, Fmax significantly increased in OZR (0.54 +/- 0.06 g). In aortas with intact PVAT, Fmax was significantly lower in all groups (0.31 +/- 0.06 OZR-C, 0.30 +/- 0.05 OZR-WB, 0.29 +/- 0.03 LZR-C, and 0.30 +/- 0.04 g LZR-WB), but no difference was observed between treatments. PVAT concentrations of monocyte chemoactractant protein 1 (MCP-1), tumor necrosis factor alpha, and adiponectin were significantly higher in OZR compared with LZR (+102%, +108%, and +45%, respectively). Following WB diet, PVAT concentrations of interleukin-8 were significantly lower in both OZR ( 37%) and LZR (-30%), while adiponectin concentrations significantly increased in both OZR (+11%) and LZR (+16%). MCP-1 concentrations significantly decreased ( 31%) in the PVAT of OZR with the WB diet. WB consumption appears to attenuate local inflammation in PVAT, which may impact systemic vascular inflammation and endothelial function. PMID- 27669021 TI - Salivary Gland Proteome during Adult Development and after Blood Feeding of Female Anopheles dissidens Mosquitoes (Diptera: Culicidae). AB - Understanding changes in mosquito salivary proteins during the time that sporozoite maturation occurs and after blood feeding may give information regarding the roles of salivary proteins during the malarial transmission. Anopheles dissidens (formerly Anopheles barbirostris species A1) is a potential vector of Plasmodium vivax in Thailand. In this study, analyses of the proteomic profiles of female An. dissidens salivary glands during adult development and after blood feeding were carried out using two-dimensional gel electrophoresis coupled with nano-liquid chromatography-mass spectrometry. Results showed at least 17 major salivary gland proteins present from day one to day 21 post emergence at 8 different time points sampled. Although there was variation observed, the patterns of protein expression could be placed into one of four groups. Fifteen protein spots showed significant depletion after blood feeding with the percentages of the amount of depletion ranging from 8.5% to 68.11%. The overall results identified various proteins, including a putative mucin-like protein, an anti-platelet protein, a long form D7 salivary protein, a putative gVAG protein precursor, a D7-related 3.2 protein, gSG7 salivary proteins, and a gSG6 protein. These results allow better understanding of the changes of the salivary proteins during the adult mosquito development. They also provide candidate proteins to investigate any possible link or not between sporozoite maturation, or survival of skin stage sporozoites, and salivary proteins. PMID- 27669023 TI - Enhanced flexoelectric-like response in oxide semiconductors. AB - Flexoelectricity is a property of all dielectric materials whereby they polarize in response to deformation gradients such as those produced by bending. Although it is generally thought of as a property of dielectric insulators, insulation is not a formal requirement: in principle, semiconductors can also redistribute their free charge in response to strain gradients. Here we show that bending a semiconductor not only generates a flexoelectric-like response, but that this response can in fact be much larger than in insulators. By doping single crystals of wide-bandgap oxides to increase their conductivity, their effective flexoelectric coefficient was increased by orders of magnitude. This large response can be explained by a barrier-layer mechanism that remains important even at the macroscale, where conventional (insulator) flexoelectricity otherwise tends to be small. Our results open up the possibility of using semiconductors as active ingredients in electromechanical transducer applications. PMID- 27669022 TI - A cross-modal genetic framework for the development and plasticity of sensory pathways. AB - Modality-specific sensory inputs from individual sense organs are processed in parallel in distinct areas of the neocortex. For each sensory modality, input follows a cortico-thalamo-cortical loop in which a 'first-order' exteroceptive thalamic nucleus sends peripheral input to the primary sensory cortex, which projects back to a 'higher order' thalamic nucleus that targets a secondary sensory cortex. This conserved circuit motif raises the possibility that shared genetic programs exist across sensory modalities. Here we report that, despite their association with distinct sensory modalities, first-order nuclei in mice are genetically homologous across somatosensory, visual, and auditory pathways, as are higher order nuclei. We further reveal peripheral input-dependent control over the transcriptional identity and connectivity of first-order nuclei by showing that input ablation leads to induction of higher-order-type transcriptional programs and rewiring of higher-order-directed descending cortical input to deprived first-order nuclei. These findings uncover an input dependent genetic logic for the design and plasticity of sensory pathways, in which conserved developmental programs lead to conserved circuit motifs across sensory modalities. PMID- 27669024 TI - Evolution of global temperature over the past two million years. AB - Reconstructions of Earth's past climate strongly influence our understanding of the dynamics and sensitivity of the climate system. Yet global temperature has been reconstructed for only a few isolated windows of time, and continuous reconstructions across glacial cycles remain elusive. Here I present a spatially weighted proxy reconstruction of global temperature over the past 2 million years estimated from a multi-proxy database of over 20,000 sea surface temperature point reconstructions. Global temperature gradually cooled until roughly 1.2 million years ago and cooling then stalled until the present. The cooling trend probably stalled before the beginning of the mid-Pleistocene transition, and pre dated the increase in the maximum size of ice sheets around 0.9 million years ago. Thus, global cooling may have been a pre-condition for, but probably is not the sole causal mechanism of, the shift to quasi-100,000-year glacial cycles at the mid-Pleistocene transition. Over the past 800,000 years, polar amplification (the amplification of temperature change at the poles relative to global temperature change) has been stable over time, and global temperature and atmospheric greenhouse gas concentrations have been closely coupled across glacial cycles. A comparison of the new temperature reconstruction with radiative forcing from greenhouse gases estimates an Earth system sensitivity of 9 degrees Celsius (range 7 to 13 degrees Celsius, 95 per cent credible interval) change in global average surface temperature per doubling of atmospheric carbon dioxide over millennium timescales. This result suggests that stabilization at today's greenhouse gas levels may already commit Earth to an eventual total warming of 5 degrees Celsius (range 3 to 7 degrees Celsius, 95 per cent credible interval) over the next few millennia as ice sheets, vegetation and atmospheric dust continue to respond to global warming. PMID- 27669026 TI - Health Information Technology Interoperability and Use for Better Care and Evidence. PMID- 27669025 TI - Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. AB - Bacterial adaptive immune systems use CRISPRs (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage. Although most prokaryotic adaptive immune systems generally target DNA substrates, type III and VI CRISPR systems direct interference complexes against single-stranded RNA substrates. In type VI systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease (RNase). How this enzyme acquires mature CRISPR RNAs (crRNAs) that are essential for immune surveillance and how it carries out crRNA-mediated RNA cleavage remain unclear. Here we show that bacterial C2c2 possesses a unique RNase activity responsible for CRISPR RNA maturation that is distinct from its RNA-activated single-stranded RNA degradation activity. These dual RNase functions are chemically and mechanistically different from each other and from the crRNA-processing behaviour of the evolutionarily unrelated CRISPR enzyme Cpf1 (ref. 11). The two RNase activities of C2c2 enable multiplexed processing and loading of guide RNAs that in turn allow sensitive detection of cellular transcripts. PMID- 27669028 TI - Polymyxin B Direct Hemoperfusion Using Regional Citrate-Calcium Anticoagulation: A Case Report. AB - Direct hemoperfusion with polymyxin B (PMX-DHP) is an extracorporeal treatment to add to conventional therapy during unresponsive endotoxic septic shock. So far, only heparin has been used as an anticoagulant during polymyxin B therapy. We present a case report of a postsurgical septic patient treated with 2 cycles of PMX-DHP using citrate anticoagulation. Monitoring of serum calcium, postcartridge calcium, and acid-base balance was performed. The treatments were accomplished without complications. To our knowledge, this is the first published report on the use of citrate anticoagulation during PMX-DHP. We conclude that citrate anticoagulation is feasible during hemoperfusion therapy in patients with increased hemorrhagic risk. PMID- 27669030 TI - Fully Automated Anesthesia and Fluid Management Using Multiple Physiologic Closed Loop Systems in a Patient Undergoing High-Risk Surgery. AB - Automated delivery of anesthesia guided by processed electroencephalogram monitoring using a closed-loop system is no longer a novel concept. However, combining multiple independent physiologic closed-loop systems together has never been documented before. The purpose of this case report was to evaluate the feasibility of automated anesthesia and fluid management based on a combination of physiological variables (bispectral index, stroke volume, and stroke volume variations) using 2 independent closed-loop systems. PMID- 27669029 TI - Anesthetic Management for Pediatric Awake Tracheostomy. AB - Awake tracheostomy is indicated for acute upper airway obstruction, when other methods of securing the airway, such as intubation and cricothyrotomy, have failed or are inappropriate. This option is rarely considered in pediatrics because of the concerns of patient cooperation and safety and has not been described in the literature. We describe the anesthetic management of an awake tracheostomy performed on a 7-year-old girl, with a large supraglottic mass obstructing the laryngeal introitus. PMID- 27669027 TI - Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution. AB - RATIONALE: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. OBJECTIVES: To identify the genetic influences of emphysema distribution in non alpha-1 antitrypsin-deficient smokers. METHODS: A total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism-, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed. MEASUREMENTS AND MAIN RESULTS: We identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution. CONCLUSIONS: This multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic approaches in chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764). PMID- 27669031 TI - Reversal of Anticoagulation With Dabigatran in an 82-Year-Old Patient With Traumatic Retroperitoneal Arterial Bleeding Using the New Antidote Idarucizumab: A Case Report. AB - Dabigatran etexilate is a direct oral anticoagulant used for the prevention of stroke in atrial fibrillation. Idarucizumab is a recently approved specific antidote that reverses the effect of dabigatran within minutes. We report the case of an 82-year-old patient with traumatic retroperitoneal arterial bleeding under anticoagulation with dabigatran etexilate. By administration of idarucizumab, we successfully normalized coagulation and saved the patient from an operation. In the course of the disease, a slight reincrease in dabigatran etexilate plasma levels was observed 2 days after the reversal, which could lead to a new onset of bleeding. PMID- 27669032 TI - Unsuccessful Redo MitraClip Procedure Leads to Acute Right Ventricular Failure in a Patient With Homozygous Familial Hypercholesterolemia and a Preexisting Atrial Septal Defect. AB - The MitraClip procedure is an emerging endovascular technique for treating mitral regurgitation and an attractive alternative for patients who are at high risk for open heart mitral valve repair or replacement. We present the case of a failed redo MitraClip procedure that led to acute right ventricular failure in a patient with homozygous familial hypercholesterolemia and a preexisting secundum atrial septal defect. We highlight the sequelae of the failed redo MitraClip procedure and the anesthetic challenges associated with the emergent redo sternotomy and cardiopulmonary bypass procedure required to replace the mitral valve and repair the tricuspid valve and atrial septal defect. PMID- 27669033 TI - Validation of the 'CHRESI' questionnaire on habits related to sun exposure during childhood. AB - Sun exposure in childhood is the main risk determinant for skin cancer in adulthood. Several questionnaires have been used to examine behaviour patterns in terms of sun exposure in childhood, but none have been subjected to a rigorous analysis of their measurement properties. To evaluate the psychometric properties of a questionnaire adapted to investigate children's sun exposure behaviour, a two-stage validation study was carried out. First, in a transverse study, the questionnaire was administered to a sample of 333 children recruited from schools, and the validity and internal consistency were analysed. Second, 32 children recruited in a hospital setting were interviewed for the test-retest analysis. All the items in the 'Photoprotection habits' category were significantly correlated. Principal components analysis showed that two components accounted for over 53% of the variance. The Cronbach's alpha coefficient was 0.63 for the first component and 0.43 for the second. In the stability analysis, the percentage of absolute agreement exceeded 70% for all the questions. The Questionnaire on Habits RElated to Sun exposure during Infancy (CHRESI) questionnaire examines sun protection habits by children. Its proven reliability, validity and stability make it a useful tool both in epidemiologic research and in the development and evaluation of campaigns to reduce the risk of skin cancer. PMID- 27669035 TI - E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis. AB - Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. In contrast, UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS 81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling. Our findings establish a central role of UFD-2 in the coordination between the DNA-repair process and the apoptotic response. PMID- 27669034 TI - Dual interaction of the Hsp70 J-protein cochaperone Zuotin with the 40S and 60S ribosomal subunits. AB - Ribosome-associated J protein-Hsp70 chaperones promote nascent-polypeptide folding and normal translational fidelity. The J protein Zuo1 is known to span the ribosomal subunits, but understanding of its function is limited. Here we present new structural and cross-linking data allowing more precise positioning of Saccharomyces cerevisiae Zuo1 near the 60S polypeptide-exit site and suggesting interactions of Zuo1 with the ribosomal protein eL31 and 25S rRNA helix 24. The junction between the 60S-interacting and subunit-spanning helices is a hinge that positions Zuo1 on the 40S yet accommodates subunit rotation. Interaction between the Zuo1 C terminus and 40S occurs via 18S rRNA expansion segment 12 (ES12) of helix 44, which originates at the decoding site. Deletions in either ES12 or the Zuo1 C terminus alter readthrough of stop codons and -1 frameshifting. Our study offers insight into how this cotranslational chaperone system may monitor decoding-site activity and nascent-polypeptide transit, thereby coordinating protein translation and folding. PMID- 27669038 TI - Prognostication in Developmental Dysplasia of the Hip Using the Ossific Nucleus Center Edge Angle. AB - BACKGROUND: The aim of this paper was to determine the prognostic potential of the ossific nucleus center edge angle (ONCEA) in patients below 5 years of age treated for developmental dysplasia of the hip (DDH) to predict final outcome and the need for a secondary procedure. METHODS: The interobserver and intraobserver reliability was calculated using the intraclass correlation coefficient for measurement of the ONCEA. The ONCEA was divided a priori into 3 groups: group A>=10 degrees, group B -9 to 9 degrees, and group C <=-10 degrees. Final outcome was measured using the McKay score and Severin classification. The presence of osteonecrosis was recorded at final follow-up. RESULTS: One hundred one patients with 133 dislocated hips underwent closed or open reduction for DDH. Mean age at presentation was 19 months with a mean age at final follow-up of 12.4 years. A significant difference was shown in a comparison of the 3 ONCEA groups using the McKay score, Severin classification, and need for a secondary procedure. Eighty seven of the 101 patients underwent ONCEA reliability measurements. The ONCEA was shown to have a mean intrarater reliability of 0.89, and a mean interrater reliability of 0.77. CONCLUSIONS: The ONCEA is a reliable measurement in predicting medium-term outcome of the hip post reduction in children under the age of 5 years with DDH and might be useful as a predictor for a secondary procedure before the age of 5 years. LEVEL OF EVIDENCE: Level III-prognostic case control study. CLINICAL RELEVANCE: This case control study shows the importance of measuring the ONCEA within 6 months of removing the final cast after reduction of a dislocated hip and its implications for further management and outcome. PMID- 27669037 TI - Substrate-translocating loops regulate mechanochemical coupling and power production in AAA+ protease ClpXP. AB - ATP-dependent proteases of the AAA+ family, including Escherichia coli ClpXP and the eukaryotic proteasome, contribute to maintenance of cellular proteostasis. ClpXP unfolds and translocates substrates into an internal degradation chamber, using cycles of alternating dwell and burst phases. The ClpX motor performs chemical transformations during the dwell and translocates the substrate in increments of 1-4 nm during the burst, but the processes occurring during these phases remain unknown. Here we characterized the complete mechanochemical cycle of ClpXP, showing that ADP release and ATP binding occur nonsequentially during the dwell, whereas ATP hydrolysis and phosphate release occur during the burst. The highly conserved translocating loops within the ClpX pore are optimized to maximize motor power generation, the coupling between chemical and mechanical tasks, and the efficiency of protein processing. Conformational resetting of these loops between consecutive bursts appears to determine ADP release from individual ATPase subunits and the overall duration of the motor's cycle. PMID- 27669039 TI - Cross-cultural Adaptation, Reliability, and Validity of the Yoruba Version of the Roland-Morris Disability Questionnaire. AB - STUDY DESIGN: A translation, cross-cultural adaptation, and psychometric analysis. OBJECTIVE: The aim of this study was to translate, cross-culturally adapt, and validate the Yoruba version of the RMDQ. SUMMARY OF BACKGROUND DATA: The Roland-Morris Disability Questionnaire (RMDQ) is a valid outcome tool for low back pain (LBP) in clinical and research settings. There seems to be no valid and reliable version of the RMDQ in the Nigerian languages. METHODS: Following the Guillemin criteria, the English version of the RMDQ was forward and back translated. Two Yoruba translated versions of the RMDQ were assessed for clarity, common language usage, and conceptual equivalence. Consequently, a harmonized Yoruba version was produced and was pilot-tested among 20 patients with nonspecific long-term LBP (NSLBP) for cognitive debriefing. The final version of the Yoruba RMDQ was tested for its construct validity and re-retest reliability among 120 and 87 patients with NSLBP, respectively. RESULTS: Pearson product moment correlation coefficient (r) of 0.82 was obtained for reliability of the Yoruba version of the RMDQ. The test-retest reliability of the Yoruba RMDQ yielded Cronbach alpha 0.932, while the intraclass correlation (ICC) ranged between 0.896 and 0.956. The analysis of the global scores of both the English and Yoruba versions of the RMDQ yielded ICC value of between 0.995 (95% confidence interval 0.996-0.997), with the item-by-item Kappa agreement ranging between 0.824 and 1.000. The external validity of RMDQ using Quadruple Visual Analogue Scale was r = -0.596 (P = 0.001). The Yoruba version of the RMDQ had no floor/ceiling effects, as no patient achieved either of the maximum or the minimum possible scores. CONCLUSION: The Yoruba version of the RMDQ has excellent reliability and validity and may be an appropriate outcome tool for clinical and research purposes among Yoruba-speaking patients with LBP. LEVEL OF EVIDENCE: 3. PMID- 27669036 TI - Skywalker-TBC1D24 has a lipid-binding pocket mutated in epilepsy and required for synaptic function. AB - Mutations in TBC1D24 cause severe epilepsy and DOORS syndrome, but the molecular mechanisms underlying these pathologies are unresolved. We solved the crystal structure of the TBC domain of the Drosophila ortholog Skywalker, revealing an unanticipated cationic pocket conserved among TBC1D24 homologs. Cocrystallization and biochemistry showed that this pocket binds phosphoinositides phosphorylated at the 4 and 5 positions. The most prevalent patient mutations affect the phosphoinositide-binding pocket and inhibit lipid binding. Using in vivo photobleaching of Skywalker-GFP mutants, including pathogenic mutants, we showed that membrane binding via this pocket restricts Skywalker diffusion in presynaptic terminals. Additionally, the pathogenic mutations cause severe neurological defects in flies, including impaired synaptic-vesicle trafficking and seizures, and these defects are reversed by genetically increasing synaptic PI(4,5)P2 concentrations through synaptojanin mutations. Hence, we discovered that a TBC domain affected by clinical mutations directly binds phosphoinositides through a cationic pocket and that phosphoinositide binding is critical for presynaptic function. PMID- 27669040 TI - Comparison of Three Reconstructive Techniques in the Surgical Management of Patients With Four-Level Cervical Spondylotic Myelopathy. AB - STUDY DESIGN: Retrospective clinical series. OBJECTIVE: To compare perioperative parameters, clinical outcomes, radiographic parameters, and complication rates of three reconstructive techniques after the anterior decompression of four-level cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: At present, the decision to treat multilevel CSM, especially four-level CSM, remains controversial. No one compares multilevel anterior cervical discectomy and fusion (mACDF), segmental anterior cervical corpectomy and fusion (sACCF) to multilevel anterior cervical discectomy and fusion with cage alone (mACDF-CA) in four-level constructs. METHODS: Between July 2006 and February 2014, 97 consecutive patients with four-level CSM were enrolled in this study and divided into sACCF (n = 39) group, mACDF (n = 31) group, and mACDF-CA (n = 27) group. The study compared perioperative parameters, complication rates, clinical and radiologic parameters of three reconstructive techniques after the anterior decompression of four-level CSM. RESULTS: The mACDF-CA group had the least bleeding and cost of index surgery compared with the sACCF group having the most bleeding and cost. Although significant pain relief and functional activity improvement have been achieved in the three groups at the final follow-up, there was no significant difference in the Japanese Orthopedic Association, SF-36 and NDI scores among the three groups (P >0.05). The mACDF group maintained the best cervical lordosis at the final follow-up, compared with the sACCF group maintained the worst cervical lordosis. Solid fusion was achieved in 87.1% of subjects in sACCF group, 90.3% in mACDF, and in 88.9% in mACDF-CA. The mACDF-CA group had a higher rate of subsidence and lower rate of dysphagia than other two groups. CONCLUSION: mACDF-CA can be considered an effective and safe alternative procedure in the treatment of the four-level CSM. LEVEL OF EVIDENCE: 4. PMID- 27669041 TI - Early Spinal Surgery Following Thoracolumbar Spinal Cord Injury: Process of Care From Trauma to Theater. AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aims of this study were to (1) determine the timing of surgery for traumatic thoracolumbar spinal cord injury (TLSCI) between 2010 and 2014 and (2) identify major delays in the process of care from accident scene to surgery. SUMMARY OF BACKGROUND DATA: Early spinal surgery may promote neurological recovery and reduce acute complications after TLSCI; however, it is difficult to achieve due to logistical issues and the frequent presence of other nonlife-threatening injuries. METHODS: Data were extracted from the medical records of 46 cases of acute traumatic TLSCI (AIS level T1-L1) aged between 15 and 70 years. Patients with life-threatening injuries, not requiring spinal surgery or with poor general health, were excluded. RESULTS: The median time to surgery was 27 hours [interquartile range (IQR): 20-43 hours] and improved from 27 hours in 2010 to 22 hours in 2014. Cases admitted via a pre-surgical hospital had a longer median time to surgery than direct surgical hospital admissions (28 vs. 24 hours, respectively). The median time from completion of radiological investigations to surgery was 18 hours, suggesting that theater access and organization of a surgical team were the major factors contributing to surgical delay. Number of vertebral levels fractured (>=5) and upper thoracic level of injury (T1-8) were also found to be associated with surgical delay. CONCLUSION: Earlier spinal surgery in TLSCI would be facilitated by direct surgical hospital admission and improved access to the operating theater and surgical teams. LEVEL OF EVIDENCE: 3. PMID- 27669042 TI - Anterior Lumbar Interbody Fusion With and Without an "Access Surgeon": A Systematic Review and Meta-analysis. AB - STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: The aim of this study was to investigate the outcomes of anterior lumber interbody fusion (ALIF) with and without an "access surgeon." SUMMARY OF BACKGROUND DATA: Anterior approaches for spine operations have become increasingly popular but may often involve unfamiliar anatomy and territory for spine surgeons, potentially placing the patient at risk to a greater proportion of approach-related complications. Thus, many spine surgeons require or prefer the assistance of an "access surgeon" to perform the exposure. However, there has been much debate about the necessity of an "access surgeon." METHODS: A systematic search of six databases from inception to April 2016 was performed by two independent reviewers. Meta-analysis was used to pool overall rates, and compare the outcomes of ALIF with an access surgeon and without. RESULTS: A total of 58 (8028 patients) studies were included in this meta-analysis. The overall intraoperative complications were similar with and without an "access surgeon." The overall pooled rate of arterial injuries [no access 0.44% vs. access 1.16%, odds ratio (OR) 2.67, P < 0.001], retrograde ejaculation (0.41% vs. 0.96%, OR 2.34, P = 0.005), and ileus (1.93% vs. 2.26%, OR 2.45, P < 0.001) was higher with an "access surgeon." However, the overall pooled rates of peritoneal injury (0.44% vs. 0.16%, OR 0.36, P = 0.034) and neurological injury (0.99% vs. 0.11%, OR 0.11, P < 0.001) were lower with an "access surgeon." Total postoperative complications (5.95% vs. 4.08%, OR 0.67, P < 0.001) were lower with an "access surgeon" along with prosthesis complications (1.59% vs. 0.89%, OR 0.56, P < 0.001) and reoperation rates (2.28% vs. 1.31%, OR 0.57, P < 0.001). CONCLUSION: Compared with no access surgeon, the use of an access surgeon was associated with similar intraoperative complication rates, higher arterial injuries, retrograde ejaculation, ileus, and lower prosthesis complications, reoperation rates, and postoperative complications. In cases wherein exposure may be difficult, support from an "access surgeon" should be available. LEVEL OF EVIDENCE: 1. PMID- 27669043 TI - Standing Balance and Compensatory Mechanisms in Patients With Adult Spinal Deformity. AB - STUDY DESIGN: A prospective case series. OBJECTIVE: The aim of this study was to compare the standing balance and posture between patients with adult spinal deformity (ASD) and healthy volunteers (HVs). SUMMARY OF BACKGROUND DATA: The effect of ASD on standing posture and balance has not been fully documented. METHODS: Forty consecutive female patients with ASD (65.4 +/- 6.7 yrs, Cobb angle 48.6 +/- 20.2 degrees , C7PL 9.1 +/- 6.4 cm, and PI-LL 41.1 +/- 25.2 degrees ) and 33 matched HV (72.4 +/- 4.6 yrs) were included. We reviewed charts and x-rays from ASDs and categorized the patients as having a PI-LL mismatch that was severe (>20 degrees ) or moderate (10 degrees 25 years; n = 31). In comparison, Group 1 was featured by significantly higher rate of recurrence and shorter overall survival, although no difference found in the surgical modality between two groups. CONCLUSION: There is a dismal prognosis in young patients with chordoma, and thus support the notion that as radical a total en bloc spondylectomy (TES) of the lesions as possible may benefit the overall survival of these young patients. Although the ensuing neurological deficits may be devastating, it will be worth sacrificing if the life expectancy of these young patients is prolonged. LEVELS OF EVIDENCE: 4. PMID- 27669049 TI - Long-term Outcome of Surgical Treatment for Superior Cluneal Nerve Entrapment Neuropathy. AB - STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: The objective of this study was to present the long-term surgical outcomes of operative treatment for superior cluneal nerve (SCN) entrapment neuropathy (SCNEN) and to analyze the causes of poor results and further treatment required. SUMMARY OF BACKGROUND DATA: There are a few reports of the outcomes of surgical treatment for SCNEN, and most studies describe results for operations conducted under general anesthesia with short follow-up periods. METHODS: Surgery was performed for SCNEN in 52 consecutive patients on 79 sides, excluding patients who had undergone previous surgery on the lumbar spine. Entrapment was unilateral in 25 patients and bilateral in 27. The mean postoperative follow-up period was 41.3 months (range, 29-58 months). All patients had received conservative treatment without improvements, and operations were performed under local anesthesia. RESULTS: Twenty-three cases (44%) involved only low-back pain (LBP), and 31 cases (60%) involved LBP associated with leg numbness or pain. The mean number of SCN branches decompressed in the operative field at the first operation was 1.4 (range, 1-4 branches). There were no local or systemic complications during or after the operation. All patients reported symptom improvement, but LBP caused by SCNEN recurrence was reported for 10 sides (13%) in seven patients who subsequently underwent repeat surgery. In the second surgery, the number of additionally treated SCN branches was 2.0 (range, 1-5). Additional surgeries were performed in two cases for lumbar disorders. All patients showed significant improvement at the last follow-up visit (P < 0.05), including those who developed recurrence. CONCLUSION: Long-term outcomes of surgical treatment for SCNEN were satisfactory. For prevention of recurrence, as many SCN branches as possible should be decompressed in the operation field during the first operation. LEVEL OF EVIDENCE: 4. PMID- 27669050 TI - Comparison of integrated behavioral health treatment for internalizing psychiatric disorders in patients with and without Type 2 diabetes. AB - INTRODUCTION: Type 2 diabetes is often comorbid with internalizing mental health disorders and associated with greater psychiatric treatment resistance. Integrating psychotherapy into primary care can help treat internalizing disorders generally. We explored whether such treatment had comparable effectiveness in patients with and without Type 2 diabetes. METHOD: Participants were 468 consecutive adults (23% male; 62% Hispanic, Mage = 41.46 years) referred by medical staff for psychotherapy appointments to address internalizing symptoms (e.g., depression). After each visit, patients completed a self-report measure and clinicians assessed patient symptom severity. These data and demographics extracted from electronic medical records were analyzed using descriptive and multilevel modeling analyses. RESULTS: Patients with and without diabetes were similar in types of internalizing disorders experienced and baseline clinician- and self-reported symptomology. Multilevel modeling suggested improvements in self-reported symptomology was comparable across patient groups; however, only patients without diabetes significantly improved according to clinician reports. DISCUSSION: Although findings suggested integrated psychotherapy resulted in comparable patient-reported reductions of internalizing symptoms, these effects were not evident in clinician reports of diabetic patients. Possible reasons for this discrepancy (e.g., reporting biases) are discussed. Integrated psychotherapy for internalizing disorders may be effective for Type 2 diabetic patients, though caution is warranted. (PsycINFO Database Record PMID- 27669051 TI - Generation of subnanometric platinum with high stability during transformation of a 2D zeolite into 3D. AB - Single metal atoms and metal clusters have attracted much attention thanks to their advantageous capabilities as heterogeneous catalysts. However, the generation of stable single atoms and clusters on a solid support is still challenging. Herein, we report a new strategy for the generation of single Pt atoms and Pt clusters with exceptionally high thermal stability, formed within purely siliceous MCM-22 during the growth of a two-dimensional zeolite into three dimensions. These subnanometric Pt species are stabilized by MCM-22, even after treatment in air up to 540 degrees C. Furthermore, these stable Pt species confined within internal framework cavities show size-selective catalysis for the hydrogenation of alkenes. High-temperature oxidation-reduction treatments result in the growth of encapsulated Pt species to small nanoparticles in the approximate size range of 1 to 2 nm. The stability and catalytic activity of encapsulated Pt species is also reflected in the dehydrogenation of propane to propylene. PMID- 27669052 TI - Memristors with diffusive dynamics as synaptic emulators for neuromorphic computing. AB - The accumulation and extrusion of Ca2+ in the pre- and postsynaptic compartments play a critical role in initiating plastic changes in biological synapses. To emulate this fundamental process in electronic devices, we developed diffusive Ag in-oxide memristors with a temporal response during and after stimulation similar to that of the synaptic Ca2+ dynamics. In situ high-resolution transmission electron microscopy and nanoparticle dynamics simulations both demonstrate that Ag atoms disperse under electrical bias and regroup spontaneously under zero bias because of interfacial energy minimization, closely resembling synaptic influx and extrusion of Ca2+, respectively. The diffusive memristor and its dynamics enable a direct emulation of both short- and long-term plasticity of biological synapses, representing an advance in hardware implementation of neuromorphic functionalities. PMID- 27669055 TI - Phonon transport in single-layer boron nanoribbons. AB - Inspired by the successful synthesis of three two-dimensional (2D) allotropes, the boron sheet has recently been one of the hottest 2D materials around. However, to date, phonon transport properties of these new materials are still unknown. By using the non-equilibrium Green's function (NEGF) combined with the first principles method, we study ballistic phonon transport in three types of boron sheets; two of them correspond to the structures reported in the experiments, while the third one is a stable structure that has not been synthesized yet. At room temperature, the highest thermal conductance of the boron nanoribbons is comparable with that of graphene, while the lowest thermal conductance is less than half of graphene's. Compared with graphene, the three boron sheets exhibit diverse anisotropic transport characteristics. With an analysis of phonon dispersion, bonding charge density, and simplified models of atomic chains, the mechanisms of the diverse phonon properties are discussed. Moreover, we find that many hybrid patterns based on the boron allotropes can be constructed naturally without doping, adsorption, and defects. This provides abundant nanostructures for thermal management and thermoelectric applications. PMID- 27669054 TI - Factors of Resilience in Informal Caregivers of People with Dementia from Integrative International Data Analysis. AB - BACKGROUND/AIMS: Although caring for a person with dementia can be stressful, some caregivers appear to experience few negative consequences to their well being. This study aimed to examine what proportion of caregivers demonstrates resilience under different challenging circumstances and to identify factors related to their resilience. METHODS: Baseline data from 4 studies from the Netherlands and UK among informal caregivers of people with dementia were harmonized and integrated. Caregiver resilience was defined as high levels of psychological well-being despite different types of high caregiving demands. Multivariate regression analyses identified factors significantly related to caregiver resilience. RESULTS: The integrated data set included 15 harmonized variables with data from 1,048 caregivers facing a high care demand. The prevalence of resilience varied between 35 and 43%, depending on the demand for high care. Being a male caregiver, caring for a female, living apart from your relative, and low caregiver burden were positively related to caregiver resilience. CONCLUSION: Caregivers have the capacity to demonstrate resilience despite significant challenges. This study demonstrates how harmonization of data from multiple existing studies can be used to increase power and explore the consistency of findings. This contributes to a better understanding of which factors are likely to facilitate caregiver resilience and offers insights for developing services. PMID- 27669053 TI - Quasicrystalline nanocrystal superlattice with partial matching rules. AB - Expanding the library of self-assembled superstructures provides insight into the behaviour of atomic crystals and supports the development of materials with mesoscale order. Here we build on recent findings of soft matter quasicrystals and report a quasicrystalline binary nanocrystal superlattice that exhibits correlations in the form of partial matching rules reducing tiling disorder. We determine a three-dimensional structure model through electron tomography and direct imaging of surface topography. The 12-fold rotational symmetry of the quasicrystal is broken in sublayers, forming a random tiling of rectangles, large triangles and small triangles with 6-fold symmetry. We analyse the geometry of the experimental tiling and discuss factors relevant for the stabilization of the quasicrystal. Our joint experimental-computational study demonstrates the power of nanocrystal superlattice engineering and further narrows the gap between the richness of crystal structures found with atoms and in soft matter assemblies. PMID- 27669058 TI - Improved Internal Quantum Efficiency and Light-Extraction Efficiency of Organic Light-Emitting Diodes via Synergistic Doping with Au and Ag Nanoparticles. AB - This paper reports the distinct roles of Au and Ag nanoparticles (NPs) in organic light-emitting diodes (OLEDs) depending on their sizes. Au and Ag NPs that are 40 and 50 nm in size, respectively, are the most effective for enhancing the performance of green OLEDs. The external quantum efficiencies (EQEs) of green OLEDs doped with Au and Ag NPs (40 and 50 nm, respectively) are improved by 29.5% and 36.1%, respectively, while the power efficiencies (PEs) are enhanced by 47.9% and 37.5%, respectively. Furthermore, combining the Au and Ag NPs produces greater enhancements. The EQE and PE of the codoped OLEDs are improved by 63.9% and 68.8%, respectively, through the synergistic behavior of the different NPs. Finite-difference time-domain simulations confirm that the localized surface plasmon resonance of the Au NPs near 580 nm improves the radiative recombination rate (krad) of green-light emitters locally (<50 nm), while the Ag NPs cause relatively long-range and broadband enhancements in krad. The simulations of various domain sizes verify that the light-extraction efficiency (LEE) can be enhanced by more than 4.2% by applying Ag NPs. Thus, size-controlled Au and Ag NPs can synergistically enhance OLEDs by improving both the internal quantum efficiency and LEE. PMID- 27669057 TI - Antifouling Electrospun Nanofiber Mats Functionalized with Polymer Zwitterions. AB - In this study, we exploit the excellent fouling resistance of polymer zwitterions and present electrospun nanofiber mats surface functionalized with poly(2 methacryloyloxyethyl phosphorylcholine) (polyMPC). This zwitterionic polymer coating maximizes the accessibility of the zwitterion to effectively limit biofouling on nanofiber membranes. Two facile, scalable methods yielded a coating on cellulose nanofibers: (i) a two-step sequential deposition featuring dopamine polymerization followed by the physioadsorption of polyMPC, and (ii) a one-step codeposition of polydopamine (PDA) with polyMPC. While the sequential and codeposited nanofiber mat assemblies have an equivalent average fiber diameter, hydrophilic contact angle, surface chemistry, and stability, the topography of nanofibers prepared by codeposition were smoother. Protein and microbial antifouling performance of the zwitterion modified nanofiber mats along with two controls, cellulose (unmodified) and PDA coated nanofiber mats were evaluated by dynamic protein fouling and prolonged bacterial exposure. Following 21 days of exposure to bovine serum albumin, the sequential nanofiber mats significantly resisted protein fouling, as indicated by their 95% flux recovery ratio in a water flux experiment, a 300% improvement over the cellulose nanofiber mats. When challenged with two model microbes Escherichia coli and Staphylococcus aureus for 24 h, both zwitterion modifications demonstrated superior fouling resistance by statistically reducing microbial attachment over the two controls. This study demonstrates that, by decorating the surfaces of chemically and mechanically robust cellulose nanofiber mats with polyMPC, we can generate high performance, free-standing nanofiber mats that hold potential in applications where antifouling materials are imperative, such as tissue engineering scaffolds and water purification technologies. PMID- 27669056 TI - Targeting the Neuropeptide Y1 Receptor for Cancer Imaging by Positron Emission Tomography Using Novel Truncated Peptides. AB - The neuropeptide Y1 receptor (Y1R) is overexpressed in many human cancers, particularly breast cancer. Due to stability issues, limited success has been achieved for Y1R imaging agents, including full length and truncated neuropeptide Y (NPY) analogues. The goal of this study was to evaluate the possibility of using radiolabeled truncated NPY analogues to visualize Y1R expression in a preclinical model of Y1R-positive tumor. Four truncated NPY analogues were synthesized based on the sequence of [Pro30, Tyr32, Leu34]NPY(28-36), also known as BVD15. We substituted Tyr5 and Arg6 with unnatural amino acids aiming to enhance plasma stability while maintaining good receptor binding affinity to Y1R. In addition, we substituted Leu4 to Lys4 in order to conjugate via an optional linker the DOTA chelator for 68Ga labeling. Receptor binding affinity and plasma stability of these compounds were evaluated. Positron emission tomography/computed tomography (PET/CT) imaging and biodistribution studies were performed using immune-compromised mice bearing HEK293T::WT and HEK293T::hY1R tumors. [Lys(Ga-DOTA)4, Bip5]BVD15 (CCZ01035), [Lys(Ahx-Ga-DOTA)4, Bip5]BVD15 (CCZ01053), and [Lys(Pip-Ga-DOTA)4, Bip5]BVD15 (CCZ01055) demonstrated good binding affinity to Y1R (Ki = 23.4-32.3 nM), while [Lys(Ga-DOTA)4, Har6]BVD15 (P05067) showed poor binding affinity (Ki > 1000 nM). In addition, CCZ01055 exhibited low binding affinity (Ki > 1000 nM) to Y2R and Y4R, demonstrating its selectivity to Y1R. The former three peptides showed improved in vitro plasma stability of 7-16% remaining intact after 1 h incubation. PET/CT imaging and biodistribution studies for 68Ga-labeled CCZ01053, CCZ01035, and CCZ01055 showed that radioactivity was mainly cleared by the renal pathway, and HEK293T::hY1R tumors were clearly visualized with minimal background activity with the latter two. Of these two tracers, [68Ga]CCZ01055 provided lower kidney accumulation and higher contrast, i.e., average uptake ratios of Y1R tumor to wild type tumor, blood, and muscle are 3.87 +/- 0.83, 4.12 +/- 1.14, and 17.6 +/- 4.64, respectively. Furthermore, Y1R tumor uptake with [68Ga]CCZ01055 was significantly reduced with coinjection of 100 MUg of peptide YY, confirming the specificity of tumor accumulation was receptor mediated. We successfully developed the first Y1R targeting truncated NPY analogues for PET imaging in a preclinical model, and [68Ga]CCZ01055 is a critical template for designing improved imaging agents to detect Y1R expressing cancers. PMID- 27669059 TI - Evaluation of Adults Born With an Oral Cleft: Aren't Adults Just Big Kids? PMID- 27669060 TI - Workforce for 21st-Century Health and Health Care. PMID- 27669061 TI - Chosen Listening Levels for Music With and Without the Use of Hearing Aids. AB - PURPOSE: The objective of this study was to describe chosen listening levels (CLLs) for recorded music for listeners with hearing loss in aided and unaided conditions. METHOD: The study used a within-subject, repeated-measures design with 13 adult hearing-aid users. The music included rock and classical samples with different amounts of audio-industry compression limiting. CLL measurements were taken at ear level (i.e., at input to the hearing aid) and at the tympanic membrane. RESULTS: For aided listening, average CLLs were 69.3 dBA at the input to the hearing aid and 80.3 dBA at the tympanic membrane. For unaided listening, average CLLs were 76.9 dBA at the entrance to the ear canal and 77.1 dBA at the tympanic membrane. Although wide intersubject variability was observed, CLLs were not associated with audiometric thresholds. CLLs for rock music were higher than for classical music at the tympanic membrane, but no differences were observed between genres for ear-level CLLs. The amount of audio-industry compression had no significant effect on CLLs. CONCLUSION: By describing the levels of recorded music chosen by hearing-aid users, this study provides a basis for ecologically valid testing conditions in clinical and laboratory settings. PMID- 27669062 TI - Detection of malignant pleural mesothelioma in exhaled breath by multicapillary column/ion mobility spectrometry (MCC/IMS). AB - Malignant pleural mesothelioma (MPM) is predominantly caused by previous asbestos exposure. Diagnosis often happens in advanced stages restricting any therapeutic perspectives. Early stage detection via breath analysis was explored using multicapillary column/ion mobility spectrometry (MCC/IMS) to detect volatile organic compounds (VOCs) in the exhaled breath of MPM patients in comparison to former occupational asbestos-exposed and non-exposed controls. Breath and background samples of 23 MPM patients, 22 asymptomatic former asbestos (AEx) workers and 21 healthy non-asbestos exposed persons were taken for analysis. After background correction, we performed a logistic least absolute shrinkage and selection operator (lasso) regression to select the most important VOCs, followed by receiver operating characteristic (ROC) analysis. MPM patients were discriminated from both controls with 87% sensitivity, 70% specificity and respective positive and negative predictive values of 61% and 91%. The overall accuracy was 76% and the area under the ROC-curve was 0.81. AEx individuals could be discriminated from MPM patients with 87% sensitivity, 86% specificity and respective positive and negative predictive values of 87% and 86%. The overall accuracy was 87% with an area under the ROC-curve of 0.86. Breath analysis by MCC/IMS allows MPM patients to be discriminated from controls and holds promise for further investigation as a screening tool for former asbestos-exposed persons at risk of developing MPM. PMID- 27669063 TI - Cytokines as Potential Biomarkers of Parkinson Disease. PMID- 27669064 TI - Eliminating Unnecessary Processes in Primary Care. PMID- 27669065 TI - Empathy: A Vital Sign for the Osteopathic Medical Profession. PMID- 27669066 TI - Preventing Chronic Nonmalignant Pain: A Family Physician's Response to the Opioid Abuse Crisis. PMID- 27669067 TI - Correlation Between Standardize Patients' Perceptions of Osteopathic Medical Students and Students' Self-Rated Empathy. AB - CONTEXT: The use of standardized patients (SPs) promotes and enhances interpersonal skill sets of medical students and provides a critical opportunity for students to display their relational competence during simulated patient encounters. OBJECTIVE: To investigate whether SPs' ratings of osteopathic medical students' empathy and interpersonal skills correlate with students' self-rated empathy. METHODS: The study used a cross-sectional quantitative design. After SP encounters, first-, second-, and third-year osteopathic medical students self rated empathy using the Jefferson Scale of Empathy medical student version. Standardized patients also assessed students' empathy using the Jefferson Scale of Patient Perceptions of Physician Empathy and interpersonal skills using the Professionalism Assessment Ratings Scale. RESULTS: Of 780 first-, second-, and third-year students, 717 students returned the survey (91.9%). In total, 383 students were women (53.4%) and 334 were men (46.6%). Of 717 SP encounters, SPs returned surveys for 648 encounters (90.3%). Ratings from SPs regarding their perceptions of osteopathic medical students' empathetic abilities and interpersonal skills did not correlate with students' self-rated empathy scores. Second- and third-year students were perceived by SPs as having better-developed empathetic and interpersonal skill sets when compared with first-year students. Results of SPs' ratings indicated that the higher the interpersonal skills, the higher the SP-perceived empathy for students across all years (r=0.66; P<.001). CONCLUSION: Students' self-rated empathy did not correlate with SP-perceived empathy. However, the findings validated that students' core relational competencies increase as they progress through medical school. PMID- 27669068 TI - Validation of a Functional Pyelocalyceal Renal Model for the Evaluation of Renal Calculi Passage While Riding a Roller Coaster. AB - CONTEXT: The identification and evaluation of activities capable of dislodging calyceal renal calculi require a patient surrogate or validated functional pyelocalyceal renal model. OBJECTIVE: To evaluate roller coaster facilitation of calyceal renal calculi passage using a functional pyelocalyceal renal model. METHODS: A previously described adult ureteroscopy and renoscopy simulator (Ideal Anatomic) was modified and remolded to function as a patient surrogate. Three renal calculi of different sizes from the patient who provided the original computed tomographic urograph on which the simulator was based were used. The renal calculi were suspended in urine in the model and taken for 20 rides on the Big Thunder Mountain Railroad roller coaster at Walt Disney World in Orlando, Florida. The roller coaster rides were analyzed using variables of renal calculi volume, calyceal location, model position on the roller coaster, and renal calculi passage. RESULTS: Sixty renal calculi rides were analyzed. Independent of renal calculi volume and calyceal location, front seating on the roller coaster resulted in a passage rate of 4 of 24. Independent of renal calculi volume and calyceal location, rear seating on the roller coaster resulted in a passage rate of 23 of 36. Independent of renal calculi volume in rear seating, calyceal location differed in passage rates, with an upper calyceal calculi passage rate of 100%; a middle calyceal passage rate of 55.6%; and a lower calyceal passage rate of 40.0%. CONCLUSION: The functional pyelocalyceal renal model serves as a functional patient surrogate to evaluate activities that facilitate calyceal renal calculi passage. The rear seating position on the roller coaster led to the most renal calculi passages. PMID- 27669069 TI - A.T. Still's Osteopathic Lesion Theory and Evidence-Based Models Supporting the Emerged Concept of Somatic Dysfunction. AB - Andrew Taylor Still, MD, DO, coined the original idea of lesion based on the obstruction of flow of body fluids, but primarily referring to bony structures and more precisely to the spine. Throughout the 20th century, this idea was shaped and developed into the concept of somatic dysfunction, a term that is familiar to both US-trained osteopathic physicians and foreign-trained osteopaths and has been an essential cornerstone of osteopathic practice and teaching. The present historical narrative review offers an overview of the evolution of Still's original lesion concept, major evidence-based models of somatic dysfunction that attempt to explain the clinical findings, and a critique of the concept. PMID- 27669070 TI - Using Patient Perspective Sessions to Increase Empathy and Recall in Preclinical Medical Students. AB - CONTEXT: At the author's institution, patient perspective sessions were added to the preclinical curricula, in which actual patients present their medical stories and experiences to large groups of first- and second-year medical students. This curricular approach was designed to help address concerns about limited patient interaction during these years, which could lead to empathy erosion, academic burnout, and poor memory retention. OBJECTIVE: To determine whether patient perspective sessions conducted in the first and second years of medical school had an effect on students' empathy toward patients and perceived retention of material. METHODS: In the summer of 2014, an anonymous electronic survey was sent to medical students in the class of 2016 who had completed the mandatory patient perspective curricula. The patient perspective sessions had started in the academic year of 2012-2013, and they involved real patients who presented their medical stories and experiences in the medical setting. RESULTS: Of 135 surveys sent, 43 completed surveys (32%) were returned. Twenty-seven respondents (89%) reported that the patient perspective sessions met the objective of "enhancing empathy toward the patient experience," and 23 respondents (75%) reported that the sessions made the material easier to remember. Further, 24 respondents (91%) reported enjoying the sessions, and all respondents reported that they wanted the patient perspective sessions to continue. CONCLUSION: Patient perspective sessions are a unique way to add more clinical exposure to the preclinical curriculum. These sessions have the potential to increase students' empathy toward patients, to increase their retention of material, and to provide new perspective. Further, students reported enjoying the sessions, which can help decrease the potential for academic burnout. PMID- 27669072 TI - Requirements for Certification in Surgery: A Comparison of the American Board of Surgery and the American Osteopathic Board of Surgery. AB - In early 2014, the Accreditation Council for Graduate Medical Education, the American Osteopathic Association, and the American Association of Colleges of Osteopathic Medicine agreed to a memorandum of understanding describing a single accreditation system for graduate medical education in the United States. Although there are many benefits, such as consistent quality of graduate medical education, alignment of competency standards, alignment with policymakers' expectations, unification of voices on graduate medical education access and funding issues, and visibility of osteopathic medicine, there are also many challenges in creating a uniform system of graduate medical education. The authors review the pathways to initial certification for both the American Board of Surgery and the American Osteopathic Board of Surgery and discuss recertification and maintenance of certification. PMID- 27669071 TI - Effect of Medical Education on Empathy in Osteopathic Medical Students. AB - CONTEXT: Empathy is an integral component of the patient-physician relationship and involves a cognitive ability to connect with others in a meaningful fashion. Multiple longitudinal studies have shown that self-reported allopathic medical student empathy declines significantly during year 3. However, to date, only 4 cross-sectional studies have been published on osteopathic medical students' empathy. Whereas studies of allopathic medical students reported a decline in empathy, similar results were not found in osteopathic studies. OBJECTIVE: To investigate (1) self-reported empathy through years 1 to 3 of osteopathic medical students and (2) whether empathy declines during year 3. DESIGN: Design included cross-sectional and test-retest data collection. SETTING: Private osteopathic medical school in the Northeast region of the United States. PARTICIPANTS: Osteopathic medical students. MAIN OUTCOME MEASURE: The Jefferson Scale of Empathy medical student version. RESULTS: Respondents (N=717) included 383 women (53%) and 334 men (47%). When empathy levels were examined by demographics, the only significant finding was that women reported significantly higher empathy levels than men (112.3 vs 109.3; P<.001). Cross-sectional results indicate that mean empathy levels were significantly lower for third-year students at the end of the year (108.7) compared with first- and second-year students at the beginning of the year (111.3 and 112.4, respectively; P<.05). Test-retest analyses of year 3 indicated significantly lower empathy levels from the beginning to the end of the academic year (111.2 and 108.7, respectively; P<.05). CONCLUSION: Osteopathic medical students' empathy declined significantly during year 3, which is consistent with the findings from allopathic samples but differs from findings from osteopathic samples. More research is needed to build the data on osteopathic medical student samples and to achieve a better understanding of changes in empathy in osteopathic and allopathic medical students. PMID- 27669073 TI - Japanese Massage Improves Shoulder Range of Motion in Elderly Patients With Late Stage Parkinson Disease. PMID- 27669074 TI - Manual Therapy and OMT May Be of Benefit in the Management of Somatosensory Tinnitus. PMID- 27669075 TI - Manual Therapy Shown To Improve Diabetic Foot Ulcer Healing. PMID- 27669077 TI - Transcendence From Patient-Centered Care to Person-Centered Care: A Study of the Biopsychosocial Impact of Personality on Health. PMID- 27669076 TI - Ineffectiveness of Spinal Manipulation for Acute Musculoskeletal Thoracic or Chest Wall Pain. PMID- 27669078 TI - Porphyria Cutanea Tarda. PMID- 27669079 TI - Experimental and Chemoinformatics Study of Tautomerism in a Database of Commercially Available Screening Samples. AB - We investigated how many cases of the same chemical sold as different products (at possibly different prices) occurred in a prototypical large aggregated database and simultaneously tested the tautomerism definitions in the chemoinformatics toolkit CACTVS. We applied the standard CACTVS tautomeric transforms plus a set of recently developed ring-chain transforms to the Aldrich Market Select (AMS) database of 6 million screening samples and building blocks. In 30 000 cases, two or more AMS products were found to be just different tautomeric forms of the same compound. We purchased and analyzed 166 such tautomer pairs and triplets by 1H and 13C NMR to determine whether the CACTVS transforms accurately predicted what is the same "stuff in the bottle". Essentially all prototropic transforms with examples in the AMS were confirmed. Some of the ring-chain transforms were found to be too "aggressive", i.e. to equate structures with one another that were different compounds. PMID- 27669080 TI - Innovation in Medicine and Device Development, Regulatory Review, and Use of Clinical Advances. PMID- 27669081 TI - Intersystem Crossing in Diplatinum Complexes. AB - Intersystem crossing (ISC) in solid [(C4H9)4N]4[Pt2(MU-P2O5(BF2)2)4], abbreviated Pt(pop-BF2), is remarkably slow for a third-row transition metal complex, ranging from tauISC ~ 0.9 ns at 310 K to tauISC ~ 29 ns below 100 K. A classical model based on Boltzmann population of one temperature-independent and two thermally activated pathways was previously employed to account for the ISC rate behavior. An alternative we prefer is to treat Pt(pop-BF2) ISC quantum mechanically, using expressions for multiphonon radiationless transitions. Here we show that a two channel model with physically plausible parameters can account for the observed ISC temperature dependence. In channel 1, 1A2u intersystem crosses directly into 3A2u using a high energy B-F or P-O vibration as accepting mode, resulting in a temperature-independent ISC rate. In channel 2, ISC occurs via a deactivating state of triplet character (which then rapidly decays to 3A2u), using Pt-Pt stretching (160 cm-1) as a distorting mode to provide the energy needed. Fitting indicates that the deactivating state, 3X, is moderately displaced (S = 0.5-3) and blue-shifted (DeltaE = 1420-2550 cm-1) from 1A2u. Our model accounts for the experimental observation that ISC in both temperature independent and thermally activated channels is faster for Pt(pop) than for Pt(pop-BF2): in the temperature independent channel because O-H modes in the former more effectively accept than B-F modes in the latter, and in the thermally activated pathway because the energy gap to 3X is larger in the latter complex. PMID- 27669082 TI - Photoisomerization of Self-Assembled Monolayers of Azobiphenyls: Simulations Highlight the Role of Packing and Defects. AB - We present surface hopping simulations of the photodynamics of self-assembled monolayers (SAMs) of 4'-(biphenyl-4-ylazo)-biphenyl-4-thiol (ABPT) on Au(111). We show that trans -> cis photoisomerization is suppressed because of steric hindrance in a well-ordered SAM. Photoisomerization is instead viable in the presence of defects. Two particularly important defects are the boundaries between domains of trans-ABPT molecules leaning in different directions (a line defect) and single cis molecules embedded in a SAM of trans (a point defect). Our findings explain the cooperative behavior observed during the photoisomerization of a trans-ABPT SAM, leading to large domains of pure cis and trans isomers. The line and point defects are predicted to produce different patterns of cis-ABPT molecules during the early stages of the photoconversion. PMID- 27669083 TI - Managing an unstable subluxated intraocular lens with uncontrolled intraocular pressure and progressing glaucoma: July consultation #1. PMID- 27669084 TI - July consultation #2. PMID- 27669086 TI - July consultation #5. PMID- 27669085 TI - July consultation #3. PMID- 27669087 TI - July consultation #4. PMID- 27669088 TI - July consultation #6. PMID- 27669089 TI - July consultation #7. PMID- 27669090 TI - July consultation #8. PMID- 27669091 TI - Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877. AB - A multiplatform mass spectrometry-based approach was used for elucidating extracellular lipids with biosurfactant properties produced by the oleaginous yeast Rhodotorula babjevae UCDFST 04-877. This strain secreted 8.6 +/- 0.1 g/L extracellular lipids when grown in a benchtop bioreactor fed with 100 g/L glucose in medium without addition of hydrophobic substrate, such as oleic acid. Untargeted reversed-phase liquid chromatography-quadrupole/time-of-flight mass spectrometry (QTOFMS) detected native glycolipid molecules with masses of 574-716 Da. After hydrolysis into the fatty acid and sugar components and hydrophilic interaction chromatography-QTOFMS analysis, the extracellular lipids were found to consist of hydroxy fatty acids and sugar alcohols. Derivatization and chiral separation gas chromatography-mass spectrometry (GC-MS) identified these components as d-arabitol, d-mannitol, (R)-3-hydroxymyristate, (R)-3 hydroxypalmitate, and (R)-3-hydroxystearate. In order to assemble these substructures back into intact glycolipids that were detected in the initial screen, potential structures were in-silico acetylated to match the observed molar masses and subsequently characterized by matching predicted and observed MS/MS fragmentation using the Mass Frontier software program. Eleven species of acetylated sugar alcohol esters of hydroxy fatty acids were characterized for this yeast strain. PMID- 27669092 TI - Pin-Based Flow Injection Electroanalysis. AB - This work describes the use of mass-fabricated stainless-steel pins as new low cost electrodes for a flow injection analysis (FIA) system with electrochemical detection. The pins serving as electrodes are directly punched in the tubing where solutions flow, being one of the simplest flow cells for FIA. This cell consists of a carbon ink coated pin as working electrode and two bare pins as counter and reference electrodes. The pins are able to perform at least 300 measurements. Moreover, they can be easily replaced showing good repeatability and reproducibility (RSD lower than 6% in all the cases). As a proof-of-concept, the feasibility of the system to determine glucose was evaluated by an enzymatic assay using glucose oxidase, horseradish peroxidase, and ferrocyanide as electron transfer mediator. The application of this system to real food samples has shown accurate results. PMID- 27669093 TI - How is the effect of adolescent e-cigarette use on smoking onset mediated: A longitudinal analysis. AB - E-cigarette use by adolescents has been related to onset of cigarette smoking but there is little knowledge about the process(es) through which this occurs. Accordingly, we tested the role of cognitive and social factors for mediating the relation between e-cigarette use and smoking onset. A school-based survey was conducted with a baseline sample of 2,338 students in Hawaii (9th and 10th graders, mean age 14.7 years) who were surveyed in 2013 (Time 1, T1) and followed up 1 year later (Time 2, T2). We assessed e-cigarette use, cigarette smoking, demographic covariates, and 4 hypothesized mediators: smoking-related expectancies, prototypes, and peer affiliations as well as marijuana use. The primary structural modeling analysis, based on initial never-smokers, used an autoregressive model (entering T2 mediator values adjusted for T1 values) to test for mediational pathways in the relation between e-cigarette use at T1 and cigarette smoking status at T2. Results showed that e-cigarette use was related to all of the mediators. Tests of indirect effects indicated that changes in expectancies, affiliations, and marijuana use were significant pathways in the relation between e-cigarette use and smoking onset. A direct effect from e cigarette use to smoking onset was nonsignificant. Findings were replicated across autoregressive and prospective models. We conclude that the relation between adolescent e-cigarette use and smoking onset is in part attributable to cognitive and social processes that follow from e-cigarette use. Further research is needed to understand the relative role of nicotine and psychosocial factors in smoking onset. (PsycINFO Database Record PMID- 27669094 TI - Briefer assessment of social network drinking: A test of the Important People Instrument-5 (IP-5). AB - The Important People instrument (IP; Longabaugh et al., 2010) is one of the most commonly used measures of social network drinking. Although its reliability and validity are well-supported, the length of the instrument may limit its use in many settings. The present study evaluated whether a briefer, 5-person version of the IP (IP-5) adequately reproduces scores from the full IP. College freshmen (N = 1,053) reported their own past-month drinking, alcohol-related consequences, and information about drinking in their close social networks at baseline and 1 year later. From this we derived network members' drinking frequency, percentage of drinkers, and percentage of heavy drinkers, assessed for up to 10 (full IP) or 5 (IP-5) network members. We first modeled the expected concordance between full IP scores and scores from simulated shorter IP instruments by sampling smaller subsets of network members from full IP data. Then, using quasi-experimental methods, we administered the full IP and IP-5 and compared the 2 instruments' score distributions and concurrent and year-lagged associations with participants' alcohol consumption and consequences. Most of the full-IP variance was reproduced from simulated shorter versions of the IP (ICCs >= 0.80). The full IP and IP-5 yielded similar score distributions, concurrent associations with drinking (r = 0.22 to 0.52), and year-lagged associations with drinking. The IP-5 retains most of the information about social network drinking from the full IP. The shorter instrument may be useful in clinical and research settings that require frequent measure administration, yielding greater temporal resolution for monitoring social network drinking. (PsycINFO Database Record PMID- 27669095 TI - Sedentary college student drinkers can start exercising and reduce drinking after intervention. AB - Heavy drinking by college students is exceedingly harmful to the individuals and to the overall college environment. Current interventions to reduce drinking and negative consequences are infrequently utilized. This randomized clinical trial examined an alternative approach that sought to increase exercise behavior, a substance free activity, in sedentary heavy drinking college students. Participants (N = 70) were randomized to an 8-week exercise intervention: (a) motivational interviewing plus weekly exercise contracting (MI + EC) or (b) motivational interviewing and weekly contingency management for exercise (MI + CM). Follow-up evaluations occurred at posttreatment (2 months) and 6 months post baseline. Participants in both interventions significantly increased exercise frequency initially, and the MI + CM participants exercised significantly more than the MI + EC intervention participants during the intervention period (d = 1.70). Exercise behavior decreased during the follow-up period in both groups. Significant reductions in drinking behaviors and consequences were noted over time, but were not related to changes in exercise or the interventions (ds <= 0.01). This study underscores the complex nature of promoting 1 specific health behavior change with the goal of changing another. (PsycINFO Database Record PMID- 27669097 TI - Mechanistic Perspectives on Organic Photoredox Catalysis for Aromatic Substitutions. AB - Photoredox catalysis has emerged as a powerful tool for the utilization of visible light to drive chemical reactions between organic molecules that exhibit two rather ubiquitous properties: colorlessness and redox-activity. The photocatalyst, however, requires significant absorption in the visible spectrum and reversible redox activity. This very general framework has led to the development of several new modes of reactivity based on electron and energy transfer steps between photoexcited catalyst states and various organic molecules. In the past years, major effort has been devoted to photoredox catalytic aromatic substitutions involving an initial reductive activation of various aryl electrophiles by the photocatalyst, which opens a new entry into selective arene functionalizations within organic synthesis endeavors. This, however, has led to a unilateral emphasis of synthetic developments including catalyst modifications, substrate scope studies, and combinations with other chemical processes. This Account summarizes recent reports of new protocols for the synthesis of aromatic esters, thioethers, boronates, sulfonates, heterobiaryls, deuteroarenes, and other functionalized arenes under mild photoredox conditions with organic dyes. On the other hand, mechanistic studies were largely neglected. This Account emphasizes the most relevant experiments and techniques, which can greatly assist in the exploration of the mechanistic foundation of aromatic photoredox substitutions and the design of new chemical reactivities. The nature and physicochemical properties of the employed organic dyes, the control of its acid-base chemistry, the choice of the irradiation sources, and the concentrations of substrates and dyes are demonstrated to decisively affect the activity of organic photocatalysts, the chemo- and regioselectivities of reactions, and the operating mechanisms. Several methods of distinction between photocatalytic and radical chain processes are being discussed such as the determination of quantum yields by conventional actinometric studies or modern photon counter devices. Careful analyses of key thermodynamic and kinetic data of the single electron transfer steps involved in aromatic photoredox substitutions by experimental and theoretical techniques are being exemplified with recent examples from the literature including the determination of redox potentials by DFT and CV, fluorescence quenching studies, and transient absorption/emission spectroscopy. This Account provides the uninitiated reader with an overview of the potential of organic photoredox catalysis for aromatic substitution reactions and encourages the practitioners to consult highly instructive synthetic, mechanistic, theoretical, and spectroscopic tools that are available in research laboratories. PMID- 27669098 TI - A Mechanosensor Mechanism Controls the G-Quadruplex/i-Motif Molecular Switch in the MYC Promoter NHE III1. AB - MYC is overexpressed in many different cancer types and is an intensively studied oncogene because of its contributions to tumorigenesis. The regulation of MYC is complex, and the NHE III1 and FUSE elements rely upon noncanonical DNA structures and transcriptionally induced negative superhelicity. In the NHE III1 only the G quadruplex has been extensively studied, whereas the role of the i-motif, formed on the opposite C-rich strand, is much less understood. We demonstrate here that the i-motif is formed within the 4CT element and is recognized by hnRNP K, which leads to a low level of transcription activation. For maximal hnRNP K transcription activation, two additional cytosine runs, located seven bases downstream of the i-motif-forming region, are also required. To access these additional runs of cytosine, increased negative superhelicity is necessary, which leads to a thermodynamically stable complex between hnRNP K and the unfolded i motif. We also demonstrate mutual exclusivity between the MYC G-quadruplex and i motif, providing a rationale for a molecular switch mechanism driven by SP1 induced negative superhelicity, where relative hnRNP K and nucleolin expression shifts the equilibrium to the on or off state. PMID- 27669096 TI - RNAi Screening of the Glucose-Regulated Chaperones in Cancer with Self-Assembled siRNA Nanostructures. AB - The emerging field of RNA nanotechnology has been used to design well-programmed, self-assembled nanostructures for applications in chemistry, biology, and medicine. At the forefront of its utility in cancer is the unrestricted ability to self-assemble multiple siRNAs within a single nanostructure formulation for the RNAi screening of a wide range of oncogenes while potentiating the gene therapy of malignant tumors. In our RNAi nanotechnology approach, V- and Y-shape RNA templates were designed and constructed for the self-assembly of discrete, higher-ordered siRNA nanostructures targeting the oncogenic glucose regulated chaperones. The GRP78-targeting siRNAs self-assembled into genetically encoded spheres, triangles, squares, pentagons and hexagons of discrete sizes and shapes according to TEM imaging. Furthermore, gel electrophoresis, thermal denaturation, and CD spectroscopy validated the prerequisite siRNA hybrids for their RNAi application. In a 24 sample siRNA screen conducted within the AN3CA endometrial cancer cells known to overexpress oncogenic GRP78 activity, the self-assembled siRNAs targeting multiple sites of GRP78 expression demonstrated more potent and long-lasting anticancer activity relative to their linear controls. Extending the scope of our RNAi screening approach, the self-assembled siRNA hybrids (5 nM) targeting of GRP-75, 78, and 94 resulted in significant (50-95%) knockdown of the glucose regulated chaperones, which led to synergistic effects in tumor cell cycle arrest (50-80%) and death (50-60%) within endometrial (AN3CA), cervical (HeLa), and breast (MDA-MB-231) cancer cell lines. Interestingly, a nontumorigenic lung (MRC5) cell line displaying normal glucose regulated chaperone levels was found to tolerate siRNA treatment and demonstrated less toxicity (5-20%) relative to the cancer cells that were found to be addicted to glucose regulated chaperones. These remarkable self-assembled siRNA nanostructures may thus encompass a new class of potent siRNAs that may be useful in screening important oncogene targets while improving siRNA therapeutic efficacy and specificity in cancer. PMID- 27669099 TI - Large-Area Accurate Position Registry of Microparticles on Flexible, Stretchable Substrates Using Elastomer Templates. AB - This work introduces a robust means for excellent position registry of microparticles via a forced assembly technique on flexible or stretchable substrates. It is based on the dry powder rubbing process which allows assembly of a microparticle monolayer in a short time without requiring any solvent or thermal treatment. Elastic physical templates are used as substrates for the forced assembly in this study. Since the elastic templates can reduce the stress accumulation between the closely packed particles, they can minimize the defect formation in the particle assembly in large areas. The method can be used with powders comprising irregularly shaped particles with a relatively large size distribution that cannot be periodically ordered by conventional self-assembly. Furthermore, a non-closely packed particle array can be fabricated readily in large area, which is highly desirable for practical uses of the particle monolayers. The particle monolayers formed on the elastomer templates can be transferred to surfaces coated with thermoplastic block copolymers. Once transferred, the particle monolayers are flexible and stretchable over their entire surface. This work uses the particle monolayers on a large-area flexible substrate as photomasks to produce various photoresist patterns. PMID- 27669100 TI - Extraction of Oil from an Aqueous Emulsion by Coupling Thermal Swing with a Capillary Pump. AB - Separation of oil from water is an area of increasing interest because of the ever-increasing emphasis on reducing discharge of oily wastewater streams and for managing accidental oil spills. While several methods to separate oil from water are available, the current methods often require elaborate processing steps and/or have low extraction rates. Here, we report two simple and potentially inexpensive methods of separating oil from aqueous emulsions. The first method employs hydrophobized glass wool in a pressure-driven capillary pump, while the second method employs novel zeolite pellets the exterior surface of which is hydrophobic. These pellets selectively absorb oil from an aqueous emulsion, which can subsequently be recovered using thermal swing with hot fluid at a temperature far below the boiling point of the oil. Separation of oil with a very high yield (ca. 97%) appears possible using a combination of the two methods. PMID- 27669101 TI - Effects of the Orientation of [B5O11]7- Fundamental Building Blocks on Layered Structures Based on the Pentaborates. AB - Four new layered pentaborates Rb4Ba2.5B20O34Br, Rb2Ba4B20O34Br2, Rb4Ba2.5B20O34Cl, and KBaB5O9 have been successfully synthesized via a high temperature solution method; the former three are the first series of compounds reported in the Rb-Ba-B-O-X (X = halogen) system. Interestingly, the structures of the above compounds are composed of the same [B5O11]7- fundamental building block (FBB), which could be further linked to form 2infinity[B10O17]4- double layers for the former three compounds and 2infinity[B5O9]3- single layers for the last one. The structure comparisons among all the available anhydrous pentaborates reveal that the structures of the anionic framework are affected by the relationship between the orientation of [B5O11]7- FBB axes and the layer plane (parallel or perpendicular), which will produce the different number of terminal O atoms in the initial pentaborate blocks. The viewpoints give us a feasible way to investigate the layered structures and expand the structural diversity of borates. Furthermore, the infrared spectra, UV-vis-NIR diffuse reflectance spectra, and thermal behaviors of these compounds were also studied. PMID- 27669102 TI - Communicating Delicately: Introducing the Need to Make a Decision About the Use of Life-Sustaining Treatment. AB - The purpose of this study was to explore how clinicians introduce the need to make a decision about the use of life-sustaining treatment and how surrogates respond to these introductions during family conferences in the intensive care unit. This article focuses on the use of the perspective-display sequence as a way to introduce the decision-making conversation. In the family conferences, the perspective-display sequence involved (a) the clinician's perspective-display invitation of the surrogates' assessment of the patient's wishes, (b) the surrogates' reply or assessment, and (c) the clinician's decision proposal, which often incorporates the surrogates' assessment. Asking about the patient's wishes is a delicate way to ease into the decision-making conversation. By using the perspective-display sequence, clinicians are also participating in shared decision making; their decision proposal is co-constructed with surrogates' understanding of the patient's wishes regarding the treatment. PMID- 27669103 TI - Do You Get What You Paid For? An Examination of Products Advertised as Kratom. AB - Although some novel psychoactive substances (NPS) are newly discovered chemicals, others are traditional or indigenous substances that are introduced to new markets. One of these latter substances is a plant many people refer to as kratom. Indigenous to Southeast Asia and used for a variety of instrumental and recreational purposes, kratom has recently become available to Western drug users. Kratom is somewhat unique in that the plant contains two different psychoactive chemicals, which have both stimulant (mitragynine) and narcotic (7 hydroxymitragynine) properties. Thus, kratom may appeal to different types of drug users for reasons other than curiosity. In the current study, 15 samples of products that were either directly advertised as kratom or were listed in the results of a web search (but were not directly advertised as kratom) were purchased for testing. After laboratory testing, it was determined that all products advertised as kratom contained the active chemical mitragynine, but 7 hydroxymitragynine was not detected in any of the samples. Implications are discussed. PMID- 27669104 TI - "Drunk in Love": The Portrayal of Risk Behavior in Music Lyrics. AB - The current study investigated the prevalence of multiple risk behaviors in popular music lyrics as well as the contexts within which they occur. We conducted a content analysis of the top 20 Billboard songs from 2009 to 2013 in the genres of rap, country, adult contemporary, rock, R&B/hip-hop, and pop, coding for the presence of alcohol, marijuana, nonmarijuana drugs, and sex as well as the contexts intoxication, binging/addiction, partying/socializing, disregard for consequences, and emotional states. The contexts relationship status and degradation were also coded for when sex was present. Of the 600 songs, 212 mentioned sexual behaviors, which were most frequent in rap and R&B/hip-hop. Alcohol was the next most frequent risk behavior, again with greatest mention in rap and R&B/hip-hop. Alcohol, marijuana, and nonmarijuana drugs were most often associated with positive emotions, and sex was most often described within the context of casual relationships. Alcohol and sex were associated with disregard for consequences most often in 2011, when the "you only live once" motto was most popular. These findings are concerning because exposure to popular music is associated with increased risk behaviors for adolescents and young adults, who are the greatest consumers of music. PMID- 27669105 TI - Checking distributional assumptions for pharmacokinetic summary statistics based on simulations with compartmental models. AB - Bioequivalence (BE) studies are an essential part of the evaluation of generic drugs. The most common in vivo BE study design is the two-period two-treatment crossover design. AUC (area under the concentration-time curve) and Cmax (maximum concentration) are obtained from the observed concentration-time profiles for each subject from each treatment under each sequence. In the BE evaluation of pharmacokinetic crossover studies, the normality of the univariate response variable, e.g. log(AUC)1 or log(Cmax), is often assumed in the literature without much evidence. Therefore, we investigate the distributional assumption of the normality of response variables, log(AUC) and log(Cmax), by simulating concentration-time profiles from two-stage pharmacokinetic models (commonly used in pharmacokinetic research) for a wide range of pharmacokinetic parameters and measurement error structures. Our simulations show that, under reasonable distributional assumptions on the pharmacokinetic parameters, log(AUC) has heavy tails and log(Cmax) is skewed. Sensitivity analyses are conducted to investigate how the distribution of the standardized log(AUC) (or the standardized log(Cmax)) for a large number of simulated subjects deviates from normality if distributions of errors in the pharmacokinetic model for plasma concentrations deviate from normality and if the plasma concentration can be described by different compartmental models. PMID- 27669106 TI - Fixed Implant-Supported Full-Arch Prosthesis in Epidermolysis Bullosa With Severe Symptoms. PMID- 27669107 TI - Mental representations of vowel features asymmetrically modulate activity in superior temporal sulcus. AB - Research in auditory neuroscience illustrated the importance of superior temporal sulcus (STS) for speech sound processing. However, evidence for abstract processing beyond the level of phonetics in STS has remained elusive. In this study, we follow an underspecification approach according to which the phonological representation of vowels is based on the presence vs. absence of abstract features. We hypothesized that phonological mismatch in a same/different task is governed by underspecification: A less specified vowel in second position of same/different minimal pairs (e.g. [e]) compared to its more specified counterpart in first position (e.g. [o]) should result in stronger activation in STS than in the reverse presentation. Whole-brain analyses confirmed this hypothesis in a bilateral cluster in STS. However, this effect interacted with the feature-distance between first and second vowel and was most pronounced for a minimal, one-feature distance, evidencing the benefit of phonological information for processing acoustically minimal sound differences. PMID- 27669108 TI - Immunotherapy for malignant mesothelioma: reality check. AB - INTRODUCTION: Initial data of immune based therapy showed promise for improving malignant mesothelioma (MM) treatment. However, the results of such treatments have neither been predictable nor consistent and recent clinical studies of immune checkpoint inhibitors in MM have dampened initial enthusiasm. Areas covered: We comprehensively discuss the basis, modalities and updated results of immunotherapy in MM. An online search was conducted for relevant literature and abstracts of recent meetings. Expert commentary: Although initial studies have demonstrated proof of principle that manipulating the immune checkpoint axis holds promise in MM, results of some recent large studies using checkpoint inhibitors have been disappointing. This is not surprising given the low mutational load in MM and suggests that single agent immunotherapy has limited benefit in this disease. We believe that in order to demonstrate durable survival benefits, they will need to be used in combination approaches with other immunotherapies, vaccines or chemotherapy. PMID- 27669109 TI - Split lesion randomized comparative study between long pulsed Nd:YAG laser 532 and 1,064 nm in treatment of facial port-wine stain. AB - BACKGROUND: Lasers have been the treatment of choice for Port-wine stain (PWS). However, only one type of laser is not a panacea for all PWS malformations. This is may be due to the great heterogeneity of phenotypic presentation of this congenital anomaly as color, depth, and the site of the lesion. For the treatment of PWS, flash lamp-pumped pulsed dye laser, carbon dioxide, argon, krypton, copper bromide, frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG), and also intense pulsed light sources can be used. OBJECTIVES: To assess and compare the effectiveness of wavelength 532 and 1,064 nanometers (nm) long pulse Nd:YAG laser in the treatment of facial port-wine stain. PATIENTS AND METHODS: This was a comparative therapeutic study for the treatment of facial port-wine stain. We divided the lesion into two halves, medial and lateral, and then each half was treated by 532 or 1,064 nm Nd:YAG. The sessions were done every 4 weeks for six sessions and follow-up after 3 months, then assess the response before and after the sessions and at the end follow-up period objectively (degree of improvement, Photo comparison) and subjectively (Patient satisfaction). RESULTS: Fourteen out of nineteen patients completed all sessions of the treatment, and the other five patients were defaulted from the study due to different causes, including marriage, poor compliance for treatment, and for unknown causes. They were 13 (92.85%) females and 1 (7.15%) male. The mean age of patients was 22.07 +/- 9.003 years (range 8-44 years). Three patients (21.4%) were Fitzpatrick's skin type III and four patients (78.6%) were typed IV. There was no hypertrophy in any of the lesions. All facial PWSs lie along the distribution of the trigeminal nerve. Four patients (28.6%) have V1 (ophthalmic), 12 patients (85.7%) have V2 (maxillary), and 9 (64.3%) have V3 (mandibular). The color of PWSs was pink-red in eight patients (57.1%), dark-red in four patients (28.6%), and purple-dark two patients (14.3%). The improvement score for the halves of the PWS treated with long pulsed Nd:YAG 532 nm were: failure = 0%, mild = 14.3%, moderate = 28.6%, good = 28.6%, excellent = 28.6%, while the score for long pulsed Nd:YAG 1,064 nm were: failure = 7.1%, mild = 85.7%, moderate = 7.1%, good = 0%, excellent = 0%. There are highly significant differences between the two parameters (P-value = <0.001). The visual analog scale regarding the halves of PWS treated by long pulsed Nd:YAG 532 nm before the treatment was 5.00 +/- 0.96 and after treatment was 2.28 +/- 1.43. There is a highly significant difference between the two scores (P-value <0.001). The visual analog scale for the halves of PWS before the use of long pulsed Nd:YAG 1,064 nm was 5.14 +/- 0.77 and after treatment was 3.71 +/- 0.82. There is a highly significant difference between the two scores (P-value <0.001). At the end of follow-up period, mean score +/- SD for 532 nm was 2.28 +/- 1.43 and for 1,064 nm was 3.71 +/- 0.82. There is a highly significant difference in both wavelengths, when compared with scores for each before the treatment. In comparison, between 532 and 1,064 nm, the difference in the visual analog scale for 532 nm before and at the end of the follow-up period was 2.7143 +/- 1.069, while for 1,064 nm was 1.4286 +/- 0.513. There is a highly significant difference between the two wavelengths (P-value <0.001). The mean score for the satisfaction of long pulsed Nd:YAG 532 nm was 76 +/- 23, while for 1,064 nm was 33 +/- 8, so there is a highly significant difference between the two parameters (P-value = <0.001). None of the patients showed recurrence, scar, or hyperpigmentation after 3 months of the last treatment session. One patient developed hyperpigmentation that resolved with hydroquinone cream 4% and no scarring was seen at the end of follow-up period. CONCLUSIONS: The long pulsed Nd:YAG laser 532 nm is more effective in the treatment of superficial bright red facial PWSs than the long pulse Nd:YAG 1,064 nm. More treatment sessions may lead to better clearance of the lesions. The use of non-invasive imaging technique such as dermoscopy, skin analyzer likes spatial frequency domain imaging (SFDI) device, or confocal microscopy to assess the level of malformations and the changes before and after the treatment with each type can give a clearer view of tissue response to laser irradiation. Lasers Surg. Med. 48:852-858, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27669110 TI - Development of stable haploid strains and molecular genetic tools for Naumovozyma castellii (Saccharomyces castellii). AB - The budding yeast Naumovozyma castellii (syn. Saccharomyces castellii) has been included in comparative genomics studies and functional analyses of centromere DNA elements, and has been shown to possess beneficial traits for telomere biology research. To provide useful tools for molecular genetic approaches, we produced stable haploid heterothallic strains from an early ancestral strain derived from the N. castellii collection strain CBS 4310. To this end, we deleted the gene encoding the Ho endonuclease, which is essential for the mating type switching. Gene replacement of HO with the kanMX3 resistance cassette was performed in diploid strains, followed by sporulation and tetrad microdissection of the haploid spores. The mating type (MATa or MATalpha) was determined for each hoDelta mutant, and was stable under sporulation-inducing conditions, showing that the switching system was totally non-functional. The hoDeltastrains showed wild-type growth rates and were successfully transformed with linear DNA using the general protocol. Opposite mating types of the hoDeltastrains were mated, resulting in diploid cells that efficiently formed asci and generated viable spores when microdissected. By introduction of a point mutation in the URA3 gene, we created a uracil auxotrophic strain, and by exchanging the kanMX3 cassette for the hphMX4 cassette we show that hygromycin B resistance can be used as a selection marker in N. castellii. These haploid strains containing genetic markers will be useful tools for performing genetic analyses in N. castellii. Moreover, we demonstrate that homology regions of 200-230 bp can be successfully used for target site-specific integration into genomic loci. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27669111 TI - Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin-angiotensin system and suppression of nitric oxide system and epoxyeicosanoids. AB - The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals' lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 +/- 9 to 116 +/- 8, and 159 +/- 8 to 126 +/- 4 mmHg, respectively) and proteinuria (62 +/- 2 to 37 +/ 3, and 132 +/- 8 to 87 +/- 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1-7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease. PMID- 27669112 TI - Use of Yunnan Baiyao and epsilon aminocaproic acid in dogs with right atrial masses and pericardial effusion. AB - OBJECTIVE: To describe the utility of Yunnan Baiyao (YB) alone or in combination with epsilon aminocaproic acid (EAC) for the treatment of dogs with echocardiographically identified right atrial (RA) masses and pericardial effusion (PE). DESIGN: Retrospective case-controlled study. SETTING: Two private practice referral hospitals. ANIMALS: Client-owned dogs with RA masses and PE identified echocardiographically over a 3-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 67 dogs identified with RA masses and PE during the study period. Sixteen dogs were treated with YB alone while 8 dogs were treated with YB in combination with EAC in addition to pericardiocentesis. Forty-three dogs were treated with pericardiocentesis alone and were considered to be the control group. There was no difference between the groups in regards to signalment, physical examination abnormalities, and diagnostic test results on presentation. There was no significant difference between the 2 groups with respect to number of pericardiocenteses performed and there were no side effects attributed to the YB or EAC in any of the dogs. Median time to recurrence of clinical signs was not significantly different between the treatment (12 d, range 1-186 d) and control group (14.5 d, range 1-277 d). The median survival of dogs treated with YB alone or in combination with EAC (18 d, range 1-186 d) was also not significantly improved compared to dogs treated with pericardiocenteses alone (16 d, range 1-277 d). CONCLUSIONS: This study suggests YB alone or in combination with EAC is relatively safe but does not significantly delay recurrence of clinical signs or improve survival in dogs with RA masses and PE. Due to the small cohort size, further prospective studies evaluating these drugs and their effects on hemostasis in dogs with RA masses and PE are warranted. PMID- 27669113 TI - Biased signalling is an essential feature of TLR4 in glioma cells. AB - A distinct feature of the Toll-like receptor 4 (TLR4) is its ability to trigger both MyD88-dependent and MyD88-independent signalling, culminating in activation of pro-inflammatory NF-kappaB and/or the antiviral IRF3. Although TLR4 agonists (lipopolysaccharides; LPSs) derived from different bacterial species have different endotoxic activity, the impact of LPS chemotype on the downstream signalling is not fully understood. Notably, different TLR4 agonists exhibit anti tumoural activity in animal models of glioma, but the underlying molecular mechanisms are largely unknown. Thus, we investigated the impact of LPS chemotype on the signalling events in the human glioma cell line U251. We found that LPS of Escherichia coli origin (LPSEC) leads to NF-kappaB-biased downstream signalling compared to Salmonella minnesota-derived LPS (LPSSM). Exposure of U251 cells to LPSEC resulted in faster nuclear translocation of the NF-kappaB subunit p65, higher NF-kappaB-activity and expression of its targets genes, and higher amount of secreted IL-6 compared to LPSSM. Using super-resolution microscopy we showed that the biased agonism of TLR4 in glioma cells is neither a result of differential regulation of receptor density nor of formation of higher order oligomers. Consistent with previous reports, LPSEC-mediated NF-kappaB activation led to significantly increased U251 proliferation, whereas LPSSM-induced IRF3 activity negatively influenced their invasiveness. Finally, treatment with methyl beta-cyclodextrin (MCD) selectively increased LPSSM-induced nuclear translocation of p65 and NF-kappaB activity without affecting IRF3. Our data may explain how TLR4 agonists differently affect glioma cell proliferation and migration. PMID- 27669114 TI - Rabs and GAPs in starvation-induced autophagy. AB - Formation of autophagosomes requires vesicular trafficking from virtually every subcellular compartment to the formation site. This traffic must be tightly regulated but also adaptable as different membrane compartments will contribute varying amounts of membrane, lipids and proteins to the forming autophagosome depending on the stimulus. In mammalian cells, efforts to understand how autophagosomes form have been focused on the role of Rab proteins in autophagy. Rab proteins provide specificity through their interaction with coat proteins, vesicle tethers and SNAREs. Recent data emerging from these studies have defined a subset of Rab proteins and their regulators, the RabGAPS (GTPase activating proteins) in both autophagosome formation and maturation. This review will focus on the role of a set of RabGAPs shown to regulate autophagy, in particular TBC1D14, and its interactors, RAB11 and TRAPPIII. Through our studies on TBC1D14, we have gained an understanding of the contribution of membrane from the recycling endosome, and the role of TRAPPIII in maintaining ATG (Autophagy protein) 9 trafficking in autophagosome formation. PMID- 27669115 TI - Effect of fructose on the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase in HepG2 cells stimulated with placental lactogen. AB - BACKGROUND: High fructose intake induces disruption of lipid metabolism via AMP activated protein kinase (AMPK) signaling in the liver and peripheral tissues. Maternal lipid metabolism is physiologically altered by the activity of pregnancy hormones such as human placental lactogen (PL). To elucidate the influence of high fructose intake on hepatic lipid metabolism during pregnancy, we examined the effects of fructose on lipid metabolism via the AMPK pathway in hepatocytes stimulated with PL. METHODS: Human hepatoma cells (HepG2) were treated with D(-) fructose in the presence or absence of PL. Intracellular lipid contents were measured. The total and phosphorylated protein content of AMPK and acetyl-CoA carboxylase (ACC) was quantified by Western blotting. RESULTS: The intracellular triacylglycerol level in fructose-treated HepG2 cells decreased significantly compared with that in untreated cells in the presence, but not absence, of PL. AMPK and ACC phosphorylation increased significantly and concentration dependently in fructose-treated HepG2 cells in the presence of PL. CONCLUSION: Our results suggest that fructose treatment reduces triacylglycerol levels via AMPK/ACC signaling in PL-stimulated hepatocytes. These findings suggest that high fructose intake during pregnancy might impair lipid metabolism in the maternal liver. PMID- 27669116 TI - Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells. AB - The exocyst complex is a large conserved hetero-oligomeric complex that consists of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 subunits. It has been implicated in the targeting of vesicles for regulated exocytosis in various cell types, and is also important for targeted exocytosis of post-Golgi transport vesicles to the plasma membrane. The exocyst complex is essential for membrane growth, secretion, and function during exocytosis and endocytosis. Moreover, the individual components of the complex are thought to act on specific biological processes, such as cytokinesis, ciliogenesis, apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). As a result, recent studies suggest that the exocyst complex may be involved in several diseases such as kidney disease, neuropathogenesis, diabetes, and cancer. In this review, we focus on the diverse functions and cellular signaling pathways of the exocyst complex in various tumors. J. Cell. Physiol. 232: 939-957, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27669117 TI - Anti-inflammatory effects of infliximab in mice are independent of tumour necrosis factor alpha neutralization. AB - Infliximab (IFX) has been used repeatedly in mouse preclinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse tumour necrosis factor (TNF)-alpha. However, the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNF alpha was investigated ex vivo using enzyme-linked immunosorbent assay (ELISA), flow cytometry and Western blot. Infliximab (IFX) did not bind directly to soluble or membrane-bound mouse TNF-alpha nor did it have any effect on TNF-alpha induced nuclear factor kappa B (NF-kappaB) stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNF-alpha independent Trichuris muris-induced infection model of chronic colitis. Infection provoked severe transmural colonic inflammation by day 35 post-infection. Colonic pathology, macrophage phenotype and cell death were determined. As predicted from the in-vitro data, in-vivo treatment of T. muris-infected mice with IFX had no effect on clinical outcome, nor did it affect macrophage cell phenotype or number. IFX enhanced apoptosis of colonic immune cells significantly, likely to be driven by a direct effect of the humanized antibody itself. We have demonstrated that although IFX does not bind directly to TNF-alpha, observed anti inflammatory effects in other mouse models may be through host cell apoptosis. We suggest that more careful consideration of xenogeneic responses should be made when utilizing IFX in preclinical models. PMID- 27669119 TI - Coumarin sulfonates: As potential leads for ROS inhibition. AB - Coumarin sulfonates 4-43 were synthesized by reacting 3-hydroxy coumarin 1, 4 hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC50=54.2+/ 9.2MUM). Eleven compounds 6 (IC50=46.60+/-14.6MUM), 8 (IC50=11.50+/-6.5MUM), 15 (IC50=21.40+/-12.2MUM), 19 (IC50=5.75+/-0.86MUM), 22 (IC50=10.27+/-1.06MUM), 23 (IC50=33.09+/-5.61MUM), 24 (IC50=4.93+/-0.58MUM), 25 (IC50=21.96+/-14.74MUM), 29 (IC50=12.47+/-9.2MUM), 35 (IC50=20.20+/-13.4MUM) and 37 (IC50=14.47+/-5.02MUM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4-43 were characterized by different available spectroscopic techniques such as 1H NMR, 13C NMR, EIMS and HRMS. CHN analysis was also performed. PMID- 27669118 TI - Molecular docking studies and biological evaluation of 1,3,4-thiadiazole derivatives bearing Schiff base moieties as tyrosinase inhibitors. AB - 1,3,4-Thiadiazole derivatives bearing Schiff base moieties were designed, synthesized, and their tyrosinase inhibitory activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, 4-(((5 mercapto-1,3,4-thiadiazol-2-yl)-imino)methyl)-2-methoxy-phenol (14) exhibited superior inhibitory effect to the other compounds with an IC50 value of 0.036MUM. The structure-activity relationships (SARs) were preliminarily discussed and docking studies showed compound 14 had strong binding affinity to mushroom tyrosinase. Hydroxy might be the active groups. The inhibition kinetics study revealed that compounds (13 and 14) inhibited tyrosinase by acting as uncompetitive inhibitors. The LD50 value of the compound 14 was 5000mg/kg. PMID- 27669120 TI - Novel 1,3,4-oxadiazole/oxime hybrids: Synthesis, docking studies and investigation of anti-inflammatory, ulcerogenic liability and analgesic activities. AB - A novel group of 1,3,4-oxadaiazoles, a group known for their anti-inflammatory activity, is hybridized with nitric oxide (NO) releasing group, oxime, for its gastro-protective action and potential synergistic effect. The synthesized hybrids were evaluated for their anti-inflammatory, analgesic, antioxidant and ulcerogenic activities. Most of the tested compounds showed excellent anti inflammatory activity with compound 8e being more active than indomethacin. They also showed moderate analgesic activity but no antioxidant one. The ability of the synthesized compounds to inhibit COX-1 and COX-2 is studied and the prepared compounds were able to inhibit both COXs non-selectively with IC50s of 0.75 70.50MUM. Docking studies revealed the mode of interaction of the tested compounds into the empty pocket of the isozymes. All of the synthesized compounds interact with COXs active site with energy scores comparable to that of ibuprofen. All compounds showed a safer profile on the stomach tissue integrity compared to conventional NSAIDs. The designed strategy was applied to ibuprofen to introduce ibuprofen/oxadiazole/NO hybrid. The synthesized ibuprofen hybrid is a promising alternative to ibuprofen having similar anti-inflammatory activity but with safer GIT profile. PMID- 27669122 TI - Are subversion and conflict component parts of social cohesion?: A reply to Lindstrom. PMID- 27669121 TI - Vulnerability to unintentional injuries associated with land-use activities and search and rescue in Nunavut, Canada. AB - Injury is the leading cause of death for Canadians aged 1 to 44, occurring disproportionately across regions and communities. In the Inuit territory of Nunavut, for instance, unintentional injury rates are over three times the Canadian average. In this paper, we develop a framework for assessing vulnerability to injury and use it to identify and characterize the determinants of injuries on the land in Nunavut. We specifically examine unintentional injuries on the land (outside of hamlets) because of the importance of land-based activities to Inuit culture, health, and well-being. Semi-structured interviews (n = 45) were conducted in three communities that have varying rates of search and rescue (SAR), complemented by an analysis of SAR case data for the territory. We found that risk of land-based injuries is affected by socioeconomic status, Inuit traditional knowledge, community organizations, and territorial and national policies. Notably, by moving beyond common conceptualizations of unintentional injury, we are able to better assess root causes of unintentional injury and outline paths for prevention. PMID- 27669123 TI - "Benches become like porches": Built and social environment influences on older adults' experiences of mobility and well-being. AB - Neighbourhood environments significantly influence health and well-being, especially as people age. Our study uniquely highlights how one microscale feature (benches) influence older adults experiences of mobility and well-being, from their perspective. We also explore how these experiences affect and are affected by the social environment of the neighbourhoods where older adults live. We conducted one-on-one seated and walk-along interviews with individuals aged 60+ that live in three adjacent neighbourhoods in Vancouver, Canada. We collected data at two time points (n = 28, 2012; n = 22, 2014). We found that benches positively contributed to older adults' mobility experiences by: (i) enhancing their use and enjoyment of green and blue spaces, (ii) serving as a mobility aid, and (iii) contributing to social cohesion and social capital. To address the increased needs of an aging demographic, urban planners might consider the quality and presence of microfeatures as part of an immediate and inexpensive strategy to create supportive neighbourhoods for people of all ages and abilities. PMID- 27669124 TI - A novel role of bone morphogenetic protein-7 in the regulation of adhesion and migration of human monocytic cells. AB - BACKGROUND: Bone morphogenetic protein (BMP) 7 is abundant in atherosclerotic plaques and increases monocyte pro-coagulant activity by enhancing tissue factor (TF) expression. While several members of the BMP superfamily are able to serve as chemotactic agents for monocytes, the role of BMP-7 in regulation of monocyte motility is not known. AIMS: To assess the effect of BMP-7 on adhesive and migratory properties of human monocytes. METHODS: Chemokinesis, adhesion, and transendothelial migration of BMP-7-treated THP-1 cells and human monocytes were analysed using live-cell imaging, orbital shear, and Boyden chamber assays. Surface presentation of beta2 integrins and phosphorylation status of Akt & focal adhesion kinase (FAK) were studied by flow cytometry and Western blot. RESULTS: High levels of BMP-7 protein were detectable in intimal regions of atherosclerotic plaques; BMP-7 significantly enhanced THP-1 and monocyte chemokinetic properties in vitro (1.21+0.01 and 1.76+0.21 fold increase in crawling distance, respectively). Under orbital shear, adhesion of monocytic cells to microvascular endothelial cell (MVEC) monolayers was also significantly increased by BMP-7 (3.89+1.56 and 2.57+0.97 fold over vehicle). Moreover, BMP-7 accelerated transendothelial migration of THP-1 cells and monocytes towards MCP-1 (5.91+0.88 and 2.96+/-0.65 fold increase, respectively). BMP-7 enhanced cell surface presentation of beta2 integrins in the active conformation. Observed effects were determined to be Akt and FAK dependent, as shown by pharmacological inhibition. CONCLUSION: BMP-7 directly upregulates adhesion and migration of human monocytic cells via activation of beta2 integrins, Akt, and FAK. Our findings suggest that BMP-7 may serve as a novel contributor to atherogenesis. PMID- 27669125 TI - Effect of extremes of body weight on drug level in patient treated with standard dose of rivaroxaban for venous thromboembolism; real life experience. PMID- 27669126 TI - Endothelial cell senescence and thrombosis: Ageing clots. AB - Age is an important cardiovascular risk factor. Among others, age is associated with an increased risk to develop thrombotic cardiovascular complications, both in the arterial (acute myocardial infarction, stroke) and the venous (deep vein thrombosis, pulmonary embolism) system, which cannot be explained by the age associated increase in cardiovascular risk factors alone. A number of studies have demonstrated that the accumulation of senescent endothelial cells and specific phenotypic and functional alterations associated with endothelial cell senescence may play an important role during the development and progression of cardiovascular disease. Prevention of platelet aggregation and thrombosis as well as fibrinolysis are important functions of the endothelium lining the vasculature. Moreover, impaired proliferation and migration of local endothelial cells as well as exhaustion of endogenous endothelial repair mechanisms involving progenitor cells may also contribute to thrombosis and its complications with age by impairing re-endothelialisation. In this short review, we present and discuss important findings regarding the effects of the cardiovascular risk factor age on endothelial cell morphology and function including the senescence-associated secretory phenotype and altered expression of factors involved in thrombosis and fibrinolysis. We also summarize results from clinical and experimental studies in rodent and other models on the possible connection between endothelial senescence and thrombotic events. Furthermore, major mechanisms and pathways underlying endothelial cell senescence and models to study its pathomechanisms are presented. Finally, we briefly discuss potential targets and therapeutic options to prevent, postpone or treat endothelial senescence and thus the increased burden of thrombosis associated with age. PMID- 27669127 TI - Incidental pulmonary embolism in cancer patients: Interobserver agreement on the diagnosis and extent with a focus on distal clots. AB - BACKGROUND: The incidence of incidental pulmonary embolism (IPE) in cancer patients is increasing. There is scant information on the interobserver agreement among radiologists about the diagnosis of distal incidental clots and the actual radiologic extension of IPE. METHODS: A total of 88 contrast-enhanced computed tomography (CT) scans of cancer patients with IPE were reassessed blindly by two expert thoracic radiologists. First, 62 scans were reassessed and the interobserver agreement on most proximal extent of IPE was calculated between the two expert radiologists as well as between the initial and expert reading, using the kappa statistic. The sample was enriched with 26 additional scans for a total of 30 segmental and 29 subsegmental IPE to determine the interobserver agreement on distal clots. RESULTS: The level of agreement regarding the most proximal extent of IPE between the expert radiologists was very good (kappa 0.84; 95% CI, 0.73-0.95) and poor between the original radiologist and expert radiologists (kappa 0.39; 95% CI, 0.22-0.56). In the patients with segmental or subsegmental IPE on initial reading, the expert radiologists agreed with the segmental location in 12 out of 30 patients (40%) and with the subsegmental location in 17 out of 29 patients (59%). The interobserver agreement between the expert radiologists was good (kappa 0.68; 95% CI, 0.46-0.90) and moderate (kappa 0.48; 95% CI, 0.25-0.71), respectively. CONCLUSIONS: While the interobserver agreement between radiologists on the most proximal location of IPE in cancer patients appears to be fairly good, it decreases significantly for more distally located incidental clots. PMID- 27669128 TI - Diagnosis of congenital and infantile nephrotic syndromes in renal biopsies in Minas Gerais, Brazil: Six case reports. AB - Congenital or infantile nephrotic syndromes (CNS/INS) correspond to a heterogeneous group of rare diseases in which glomerular renal dysfunction and proteinuria are prominent. The aim of this study is to present six cases of possible CNS/INS with diagnoses based on clinical findings and especially histological, ultrastructural, and immunohistochemical characteristics of renal biopsies. Four cases are presented with diffuse mesangial sclerosis, one of them possibly part of Denys-Drash syndrome and two cases with CNS probably of the Finnish type in patients between 3 months old and 13 years old. The study focuses on the late evolution of Denys-Drash syndrome to end-stage renal disease in a 13 year-old patient and the diagnosis of diffuse mesangial sclerosis in an 8-year old patient. Thus, it contributes to a better epidemiological characterization of these syndromes, demonstrating cases of CNS/INS in infrequent age groups. PMID- 27669130 TI - Comparison of two angles of approach for trigger point dry needling of the lumbar multifidus in human donors (cadavers). AB - STUDY DESIGN: Descriptive comparison study. OBJECTIVE: To assess the accuracy of two needle angle approaches for dry needling of the lumbar multifidus. BACKGROUND: Low back pain is a leading cause of disability around the world; the lumbar multifidus plays a vital role in low back health. Manual therapy such as dry needling can improve pain mediation and motor control activation of the lumbar multifidus. Clinicians practicing dry needling at the lumbar multifidus typically use an inferomedial approach considered non-controversial. Clinicians practicing electromyography and nerve conduction studies commonly sample the lumbar multifidus in a directly posteroanterior approach that may provide another option for dry needling technique. METHODS: Four human donors were used for a total of eight needle placements-four with an inferomedial orientation and four with a posteroanterior orientation. Each needle was placed from 1 to 1.5 cm lateral to the spinous process of L4 to the depth of the lumbar lamina. Each lower lumbar spine was then dissected to determine the structures that the needle traversed and the needle's final resting place. RESULTS: All four inferomedial approach needles ended at the lamina of the vertebrae below. All four posterior anterior approach needles ended in the lamina of the same level. CONCLUSIONS: All eight needles traversed the lumbar multifidus and ended in the lumbar lamina with little possibility of the needle entering the subarachnoid space. Thus both the inferomedial and the posteroanterior angles of approach are efficacious for clinicians to use in dry needling of the lumbar mulifidus. PMID- 27669131 TI - Overcoming Legal Impediments to Physician Orders for Life-Sustaining Treatment. AB - The Physician Orders for Life-Sustaining Treatment (POLST), otherwise known as the POLST paradigm, represents the next generation in end-of-life (EOL) planning for certain patients who wish to exercise prospective control over their own medical treatment in their final days. As is true for any physician treatment orders, a POLST is written in consultation with the patient or patient's surrogate. There are a number of practical impediments to widespread adoption and implementation of the POLST paradigm in medical practice. One of these impediments has to do with some physicians' anxiety about potential negative legal repercussions they might suffer for writing or following a patient's POLST; this is the focus of the present article. After describing the POLST paradigm and physicians' anxieties about it, this article argues that the feared potential negative legal consequences of writing or following a patient's POLST are not well founded. Instead of succumbing to legal and ethical paralysis, resulting in the failure to integrate the POLST paradigm robustly into practice, physicians should feel comfortable under current and developing law to write and honor POLSTs for appropriate patients. This article explains the basis for such physician comfort. PMID- 27669133 TI - Prioritizing Cross-Disciplinary Teaching and Learning and Patient Safety in Hospital-Based Environments. AB - In this case scenario, Darvid is a medical student who perceives that practicing his physical examination of a patient at a specific time conflicts with nursing care. His predicament highlights the importance of interprofessional communication. Darvid is hesitant to communicate with the nurse, and his fear is exacerbated by the hierarchical structure of the academic health care setting, exemplified by the senior resident's dismissive response to his concerns. This paper argues that every opportunity should be made to prioritize students' learning but that the patient's needs must come first. The nurse in this case is in a position to help Darvid assess the priorities in this situation, but he must first feel comfortable discussing his concerns. Interprofessional education can serve a valuable role in facilitating open communication. PMID- 27669132 TI - The Limits of Informed Consent for an Overwhelmed Patient: Clinicians' Role in Protecting Patients and Preventing Overwhelm. AB - In this paper, we examine the limits of informed consent with particular focus on ways in which various factors can overwhelm decision-making capacity. We introduce overwhelm as a phenomenon commonly experienced by patients in clinical settings and distinguish between emotional overwhelm and informational overload. We argue that in these situations, a clinician's primary duty is prevention of harm and suggest ways in which clinicians can discharge this obligation. To illustrate our argument, we consider the clinical application of genetic sequencing testing, which involves scientific and technical information that can compromise the understanding and decisional capacity of most patients. Finally, we consider and rebut objections that this could lead to paternalism. PMID- 27669134 TI - Interprofessional Training: Not Optional in Good Medical Education. AB - Interprofessional education is a vital part of medical education, and students should not be permitted to exempt themselves from it. Physicians are part of a team, and the importance of teamwork will only increase as physician shortages continue and medical care becomes more complex. To learn to be good physicians in this emerging environment, students must appreciate the skills, strengths, and vocabularies of other professions. It is shortsighted to think that the best educators of future physicians can only be other physicians. PMID- 27669135 TI - Resisting Outdated Models of Pedagogical Domination and Subordination in Health Professions Education. AB - This case highlights a dilemma for interprofessional trainees facing a traditional health professions hierarchy rather than an interprofessional collaborative practice culture within the clinical setting. In the case, the trainee must determine the best way to confront the attending physician, if at all, as well as the best way to mediate the situation with fellow health professions trainees and team members. The commentary provides guidelines for interprofessional collaborative practice as outlined by the Interprofessional Education Collaborative competencies, including determining team members' roles and responsibilities, providing clear communication, adopting clinical huddles, and embracing a sense of inquiry during times of conflict. Role modeling of interprofessional collaborative practice by faculty is crucial in training a future generation of health care professionals who can continue to improve patient outcomes and quality of care. PMID- 27669136 TI - Walking the Walk in Team-Based Education: The Crimson Care Collaborative Clinic in Family Medicine. AB - Effective implementation of robust team-based care in the United States requires significant training for all team members. This education is integral to creating a culture of collaboration and respect among interprofessional members of the health care team. The lack of interprofessional clinical educational experiences contributes to a "hidden curriculum" that reinforces the problematic view that medicine is at the top of a hierarchy among health professions. However, learners themselves have started resisting this view by integrating cross-disciplinary team-based training into their own education. One example of learner-based leadership in interprofessional team care is the Crimson Care Collaborative at Cambridge Health Alliance, a student-faculty collaborative family medicine clinic. This successful clinic demonstrates that high-quality interprofessional clinical education can be accomplished through partnerships between educational institutions and existing patient-centered medical homes. PMID- 27669137 TI - Interprofessional Clinical Ethics Education: The Promise of Cross-Disciplinary Problem-Based Learning. AB - A review of Lin et al.'s pilot study exploring the effects of an interprofessional, problem-based learning clinical ethics curriculum on Taiwanese medical and nursing students' attitudes towards interprofessional collaboration highlights the benefits of interprofessional collaboration and offers insight into how problem-based learning might be universally applied in ethics education. Interprofessional collaboration is an ideal approach for exploring ethical dilemmas because it involves all relevant professionals in discussions about ethical values that arise in patient care. Interprofessional ethics collaboration is challenging to implement, however, given time constraints and organizational and practice demands. Nevertheless, we suggest that when professionals collaborate, they can collectively express greater commitment to the patient. We also suggest future research avenues that can explore additional benefits of interprofessional collaboration in clinical ethics. PMID- 27669138 TI - Time-out: The Professional and Organizational Ethics of Speaking Up in the OR. AB - Participation in patient safety is one concrete expression of a foundational principle of medical ethics: do no harm. Being an ethical professional requires taking action to prevent harm to patients in health care environments. Checklists and time-outs have become common patient safety tools in the US and other nations. While their use can support ethical practice, recent research has revealed their limitations and has underscored the importance of interpersonal collaboration in developing and using these patient safety tools. This article summarizes key research and discusses the professional and organizational ethics of patient safety, using the surgical time-out as a case study. PMID- 27669139 TI - Teamwork in Health Care: Maximizing Collective Intelligence via Inclusive Collaboration and Open Communication. AB - Teams offer the potential to achieve more than any person could achieve working alone; yet, particularly in teams that span professional boundaries, it is critical to capitalize on the variety of knowledge, skills, and abilities available. This article reviews research from the field of organizational behavior to shed light on what makes for a collectively intelligent team. In doing so, we highlight the importance of moving beyond simply including smart people on a team to thinking about how those people can effectively coordinate and collaborate. In particular, we review the importance of two communication processes: ensuring that team members with relevant knowledge (1) speak up when one's expertise can be helpful and (2) influence the team's work so that the team does its collective best for the patient. PMID- 27669140 TI - Overcoming Historical Separation between Oral and General Health Care: Interprofessional Collaboration for Promoting Health Equity. AB - Since the founding of dental schools as institutions distinct from medical schools, dentistry-its practice, service delivery, and insurance coverage, for example-and dental care have been kept separate from medical care in the United States. This separation is most detrimental to undeserved groups at highest risk for poor oral health. As awareness grows of the important links between oral and general health, physicians and dentists are collaborating to develop innovative service delivery and payment models that can reintegrate oral health care into medical care. Interprofessional education of medical and dental students can help produce clinicians who work together to the benefit of their patients. PMID- 27669141 TI - Shared Responsibility: Massachusetts Legislators, Physicians, and An Act Relative to Substance Use Treatment, Education, and Prevention. AB - Recent passage of the Massachusetts law, An Act Relative to Substance Use, Treatment, Education, and Prevention, represents an admirable public health approach to substance use disorder (SUD), a stigmatized chronic disease that affects some of society's most vulnerable people. With its seven-day supply limit on first-time opioid prescriptions, this legislation takes an unusual approach to state government involvement in health care. By intervening in individual physicians' practices, state legislators have entered a space traditionally reserved for clinical teams. The seven-day supply limit and the process through which it was developed highlight competing priorities and dialogue between physicians and legislators, limits of physician self-regulation, and standards of evidence in policy making and health care. Addressing these issues requires both physicians and legislators to recognize and fulfill new responsibilities in order to better assist the populations they serve. PMID- 27669142 TI - Decentering the Doctor: The Critical Value of a Patient Care Collective. AB - The rehabilitation environment is structured differently from the hospital-based environment in a way that lends itself to interdisciplinary care. Physicians work with other specialists on an interprofessional team while observing patients' participation in activities of daily living. This approach allows a patient to show rather than tell a physician what he or she can do, which helps the physician remove as many medical barriers to rehabilitation as possible. Another difference is the decentering of the physician on the health care team. Because a patient's functional status is beyond the scope of expertise of any individual health care team member, treatment plans are formed collaboratively, with input from every member of the team. The result is more comprehensive and holistic care for medically complex patients. PMID- 27669143 TI - Thrombospondin expression in myofibers stabilizes muscle membranes. AB - Skeletal muscle is highly sensitive to mutations in genes that participate in membrane stability and cellular attachment, which often leads to muscular dystrophy. Here we show that Thrombospondin-4 (Thbs4) regulates skeletal muscle integrity and its susceptibility to muscular dystrophy through organization of membrane attachment complexes. Loss of the Thbs4 gene causes spontaneous dystrophic changes with aging and accelerates disease in 2 mouse models of muscular dystrophy, while overexpression of mouse Thbs4 is protective and mitigates dystrophic disease. In the myofiber, Thbs4 selectively enhances vesicular trafficking of dystrophin-glycoprotein and integrin attachment complexes to stabilize the sarcolemma. In agreement, muscle-specific overexpression of Drosophila Tsp or mouse Thbs4 rescues a Drosophila model of muscular dystrophy with augmented membrane residence of betaPS integrin. This functional conservation emphasizes the fundamental importance of Thbs' as regulators of cellular attachment and membrane stability and identifies Thbs4 as a potential therapeutic target for muscular dystrophy. PMID- 27669144 TI - Recruitment of inhibition and excitation across mouse visual cortex depends on the hierarchy of interconnecting areas. AB - Diverse features of sensory stimuli are selectively processed in distinct brain areas. The relative recruitment of inhibitory and excitatory neurons within an area controls the gain of neurons for appropriate stimulus coding. We examined how such a balance of inhibition and excitation is differentially recruited across multiple levels of a cortical hierarchy by mapping the locations and strengths of synaptic inputs to pyramidal and parvalbumin (PV)-expressing neurons in feedforward and feedback pathways interconnecting primary (V1) and two higher visual areas. While interareal excitation was stronger in PV than in pyramidal neurons in all layer 2/3 pathways, we observed a gradual scaling down of the inhibition/excitation ratio from the most feedforward to the most feedback pathway. Our results indicate that interareal gain control depends on the hierarchical position of the source and the target, the direction of information flow through the network, and the laminar location of target neurons. PMID- 27669145 TI - A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction. AB - Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters. Transient responses utilize input from rod photoreceptors and output by the classical neurotransmitter glutamate, but adapt within minutes. In contrast, sustained responses are dominated by non-conventional signaling mechanisms: melanopsin phototransduction in ipRGCs and output by the neuropeptide PACAP, which provide stable pupil maintenance across the day. These results highlight a temporal switch in the coding mechanisms of a neural circuit to support proper behavioral dynamics. PMID- 27669146 TI - Cross-frequency synchronization connects networks of fast and slow oscillations during visual working memory maintenance. AB - Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and attentional control, respectively, of sensory information maintained in visual working memory (VWM). Within these regions, beta/gamma phase synchronization supports the integration of sensory functions, while synchronization in theta/alpha bands supports the regulation of attentional functions. A key challenge is to understand which mechanisms integrate neuronal processing across these distinct frequencies and thereby the sensory and attentional functions. We investigated whether such integration could be achieved by cross-frequency phase synchrony (CFS). Using concurrent magneto- and electroencephalography, we found that CFS was load-dependently enhanced between theta and alpha-gamma and between alpha and beta-gamma oscillations during VWM maintenance among visual, FP, and dorsal attention (DA) systems. CFS also connected the hubs of within-frequency-synchronized networks and its strength predicted individual VWM capacity. We propose that CFS integrates processing among synchronized neuronal networks from theta to gamma frequencies to link sensory and attentional functions. PMID- 27669147 TI - Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development. AB - Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. PMID- 27669148 TI - Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. AB - Cryo-EM has revealed the structures of many challenging yet exciting macromolecular assemblies at near-atomic resolution (3-4.5A), providing biological phenomena with molecular descriptions. However, at these resolutions, accurately positioning individual atoms remains challenging and error-prone. Manually refining thousands of amino acids - typical in a macromolecular assembly - is tedious and time-consuming. We present an automated method that can improve the atomic details in models that are manually built in near-atomic-resolution cryo-EM maps. Applying the method to three systems recently solved by cryo-EM, we are able to improve model geometry while maintaining the fit-to-density. Backbone placement errors are automatically detected and corrected, and the refinement shows a large radius of convergence. The results demonstrate that the method is amenable to structures with symmetry, of very large size, and containing RNA as well as covalently bound ligands. The method should streamline the cryo-EM structure determination process, providing accurate and unbiased atomic structure interpretation of such maps. PMID- 27669149 TI - Schwann cells genetically modified to express S100A4 increases GAP43 expression in spiral ganglion neurons in vitro. AB - Schwann cells (SCs) have been reported as a possible source of neurotrophic support for spiral ganglion neurons (SGNs). This study was aimed to investigate whether S100A4 was contributed in the functional effects of SCs on SGNs. SCs were transfected with S100A4 vector or small interfering RNA (siRNA) against S100A4, and the transfection efficiency was verified by quantitative PCR (qPCR) and Western blot. The migration of transfected SCs was determined by Transwell assay, and the expression levels of vascular endothelial growth factor precursor (VEGF) and matrix metallopeptidase 9 (MMP-9) were measured by Western blot. Co-culture of either S100A4 overexpressed or suppressed SCs with SGNs, and the growth associated protein 43 (GAP43) expression in SGNs was detected by immunofluorescence (IF), qPCR and Western blot. The migration of SCs was significantly enhanced by S100A4 overexpression (P < 0.001), while was suppressed by S100A4 knockdown (P < 0.01). Further, the expressions of VEGF and MMP-9 were notably up-regulated by S100A4 overexpression, while were down-regulated by S100A4 knockdown. Moreover, co-culture with the S100A4 overexpressed SCs significantly increased the expression of GAP43 in SGNs (P < 0.01). As expected, co-culture with S100A4 knockdown SCs decreased GAP43 level (P < 0.05). S100A4 enhanced the migratory ability of SCs. SCs genetically modified to overexpress the S100A4 could up-regulate the GAP43 expression in SGNs. PMID- 27669150 TI - Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality. AB - Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP) negatively influences outcomes. Following CLP mice were randomized to receive the antibiotic imipenem-cilastatin (25mg/kg) in dextrose 5% in Lactated Ringer's solution every 12 hours for either three or five days. Serial monitoring over 28 days included body weight, temperature, pulse oximetry, and facial vein sampling for hematological analysis and glucose. A separate group of mice were euthanized on post-CLP day 5 to measure cytokines and peritoneal bacterial counts. The first study examined no antimicrobial therapy and demonstrated that antibiotics significantly improved survival compared to fluids only (p = 0.004). We next tested imipenem-cilastatin therapy for 3 days versus 5 days. Body weight, temperature, glucose, and pulse oximetry measurements remained generally consistent between both groups as did the hematological profile. Pro-inflammatory plasma cytokines were comparable between both groups for IL-6, IL-1beta, MIP-2 and anti-inflammatory cytokines IL 10, and TNF SRI. At 5 days post-CLP, i.e. 2 days after the termination of antibiotics in the 3 day group, there were no differences in the number of peritoneal bacteria. Importantly, shortening the course of antibiotics by 40% (from 5 days to 3 days) did not decrease survival. Our results indicate that reducing the duration of broad-spectrum antibiotics in murine sepsis did not increase inflammation or mortality. PMID- 27669151 TI - Cerebellar tDCS Does Not Improve Learning in a Complex Whole Body Dynamic Balance Task in Young Healthy Subjects. AB - Transcranial direct current stimulation (tDCS) of the cerebellum is of increasing interest as a non-invasive technique to modulate motor performance and learning in health and disease. Previous studies have shown that cerebellar tDCS facilitates reach adaptation and associative motor learning in healthy subjects. In the present study it was tested whether cerebellar tDCS improves learning of a complex whole body motor skill. Because this task involves learning of posture and balance likely including learning of a new motor sequence and cognitive strategies, cerebellar tDCS was applied over midline cerebellar structures and the posterolateral cerebellar hemispheres. 30 young and healthy subjects performed two days of balance training on a Lafayette Instrument 16030 stability platform(r). Participants received either anodal, cathodal or sham cerebellar tDCS during training on day 1. The cerebellar electrode (7 cm width by 5 cm height) was centered 2 cm below the inion. Mean platform angle deviation and mean balance time were assessed. All subjects showed significant effects of learning. Learning rate was not different between the three modes of stimulation neither on day 1 nor on day 2. Cerebellar tDCS did not facilitate learning of a complex whole body dynamic balance task in young and healthy subjects. tDCS effects, however, may have been missed because of the small group size. Furthermore, it cannot be excluded that young and healthy subjects learned and performed already at a near optimal level with little room for further improvement. Future work has to evaluate potential benefits of cerebellar tDCS in elderly subjects and subjects with cerebellar deficits, whose motor control and motor learning network is not optimally tuned. PMID- 27669152 TI - Functional SNPs of INCENP Affect Semen Quality by Alternative Splicing Mode and Binding Affinity with the Target Bta-miR-378 in Chinese Holstein Bulls. AB - Inner centromere protein (INCENP) plays an important role in mitosis and meiosis as the main member of chromosomal passenger protein complex (CPC). To investigate the functional markers of the INCENP gene associated with semen quality, the single nucleotide polymorphisms (SNPs) g.19970 A>G and g.34078 T>G were identified and analyzed. The new splice variant INCENP-TV is characterized by the deletion of exon 12. The g.19970 A>G in the exonic splicing enhancer (ESE) motif region results in an aberrant splice variant by constructing two minigene expression vectors using the pSPL3 exon capturing vector and transfecting vectors into MLTC-1 cells. INCENP-TV was more highly expressed than INCENP-reference in adult bull testes. The g.34078 T>G located in the binding region of bta-miR-378 could affect the expression of INCENP, which was verified by luciferase assay. To analyze comprehensively the correlation of SNPs with sperm quality, haplotype combinations constructed by g.19970 A>G and g.34078 T>G, as well as g.-692 C>T and g.-556 G>T reported in our previous studies, were analyzed. The bulls with H1H12 and H2H2 exhibited a higher ejaculate volume than those with H2H10 and H9H12, respectively (P < 0.05). Bulls with H11H11 and H2H10 exhibited higher initial sperm motility than those with H2H2 (P < 0.05). The expression levels of INCENP in bulls with H1H12 and H11H11 were significantly higher than those in bulls with H9H12 (P < 0.05), as determined by qRT-PCR. Findings suggest that g.19970 A>G and g.34078 T>G in INCENP both of which appear to change the molecular and biological characteristics of the mRNA transcribed from the locus may serve as a biomarkers of male bovine fertility by affecting alternative splicing mode and binding affinity with the target bta-miR-378. PMID- 27669153 TI - Femoral Bone Marrow Insulin Sensitivity Is Increased by Resistance Training in Elderly Female Offspring of Overweight and Obese Mothers. AB - : Bone marrow insulin sensitivity may be an important factor for bone health in addition to bone mineral density especially in insulin resistant conditions. First we aimed to study if prenatal maternal obesity plays a role in determining bone marrow insulin sensitivity in elderly female offspring. Secondly we studied if a four-month individualized resistance training intervention increases bone marrow insulin sensitivity in elderly female offspring and whether this possible positive outcome is regulated by the offspring's mother's obesity status. 37 frail elderly females (mean age 71.9 +/- 3.1 years) of which 20 were offspring of lean/normal-weight mothers (OLM, maternal BMI <= 26.3 kg/m2) and 17 were offspring of obese/overweight mothers (OOM, maternal BMI >= 28.1 kg/m2) were studied before and after a four-month individualized resistance training intervention. Nine age- and sex-matched non-frail controls (maternal BMI <= 26.3 kg/m2) were studied at baseline. Femoral bone marrow (FBM) and vertebral bone marrow (VBM) insulin sensitivity were measured using [18F]fluoro-2-deoxy-D glucose positron emission tomography with computer tomography under hyperinsulinemic euglycemic clamp. We found that bone marrow insulin sensitivity was not related to maternal obesity status but FBM insulin sensitivity correlated with whole body insulin sensitivity (R = 0.487, p = 0.001). A four-month resistance training intervention increased FBM insulin sensitivity by 47% (p = 0.006) only in OOM, while VBM insulin sensitivity remained unchanged regardless of the maternal obesity status. In conclusion, FBM and VBM glucose metabolism reacts differently to a four-month resistance training intervention in elderly women according to their maternal obesity status. TRIAL REGISTRATION: ClinicalTrials.gov NCT01931540. PMID- 27669155 TI - Efficacy and safety of adjunctive lacosamide for the treatment of partial-onset seizures in Chinese and Japanese adults: A randomized, double-blind, placebo controlled study. AB - OBJECTIVE: To evaluate the efficacy and safety of adjunctive lacosamide treatment in Chinese and Japanese adults with uncontrolled focal (partial-onset) seizures (POS), with or without secondary generalization. METHODS: A 24-week, randomized, double-blind, placebo-controlled study (EP0008; NCT01710657) was conducted in patients (aged 16-70 years) with uncontrolled POS and taking 1-3 concomitant antiepileptic drugs from 72 sites across China and Japan. Following an 8-week Baseline period, randomized patients received lacosamide 200mg/day (100mg twice daily), 400mg/day (200mg twice daily), or placebo for 4-week Titration and 12 week Maintenance periods. The primary efficacy variable was the change in POS frequency per 28days from Baseline to Maintenance. RESULTS: Overall, 692 patients were screened; 548 were randomized to placebo (n=184), lacosamide 200mg/day (n=183), or lacosamide 400mg/day (n=181); 485 (88.5%) completed the study. The median change (range) in POS frequency per 28days from Baseline to Maintenance was -3.33 (-754.3 to 165.2), -4.50 (-97.5 to 28.2), and -1.22 (-93.0 to 39.8) in the lacosamide 200mg/day, 400mg/day, and placebo groups, respectively. Significant percentage reductions in POS frequency over placebo per 28days from Baseline to Maintenance were observed for lacosamide 200mg/day (29.4% [95% CI 18.7-38.7%], p<0.001) and 400mg/day (39.6% [30.5-47.6%], p<0.001). Higher >=50% and >=75% responder and seizure freedom rates were observed in lacosamide-treated patients vs placebo. Treatment-emergent adverse events reported by >=10% of all lacosamide-treated patients occurring at >=2% difference compared with placebo were dizziness (25.9% vs 9.2%) and somnolence (10.2% vs 3.8%). Dose-proportional pharmacokinetics were consistent with earlier global pivotal trials. CONCLUSIONS: Adjunctive lacosamide (200 and 400mg/day) was efficacious in reducing POS frequency in Chinese and Japanese patients with a safety and tolerability profile consistent with the three global pivotal studies. PMID- 27669154 TI - Informatics-Based Discovery of Disease-Associated Immune Profiles. AB - Advances in flow and mass cytometry are enabling ultra-high resolution immune profiling in mice and humans on an unprecedented scale. However, the resulting high-content datasets challenge traditional views of cytometry data, which are both limited in scope and biased by pre-existing hypotheses. Computational solutions are now emerging (e.g., Citrus, AutoGate, SPADE) that automate cell gating or enable visualization of relative subset abundance within healthy versus diseased mice or humans. Yet these tools require significant computational fluency and fail to show quantitative relationships between discrete immune phenotypes and continuous disease variables. Here we describe a simple informatics platform that uses hierarchical clustering and nearest neighbor algorithms to associate manually gated immune phenotypes with clinical or pre clinical disease endpoints of interest in a rapid and unbiased manner. Using this approach, we identify discrete immune profiles that correspond with either weight loss or histologic colitis in a T cell transfer model of inflammatory bowel disease (IBD), and show distinct nodes of immune dysregulation in the IBDs, Crohn's disease and ulcerative colitis. This streamlined informatics approach for cytometry data analysis leverages publicly available software, can be applied to manually or computationally gated cytometry data, is suitable for any clinical or pre-clinical setting, and embraces ultra-high content flow and mass cytometry as a discovery engine. PMID- 27669156 TI - A cross-sectional vaccination coverage study in preschool children attending nurseries-kindergartens: Implications on economic crisis effect. AB - Vaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs. This study assessed full and timely vaccination coverage of preschool children aged 2-3 y attending nurseries-kindergartens (N-K) nationwide at the socioeconomic crisis onset. Geographically stratified cluster sampling was implemented considering prefectures as strata and N-K as clusters. The N-K were selected by simple random sampling from the sampling frame while their number was proportional to the stratum size. In total, 185 N-K (response rate 93.9%) and 2539 children (response rate 81.5%) participated. Coverage with traditional vaccines for diphtheria-tetanus-pertussis, polio and measles-mumps-rubella was very high (>95%), followed by Haemophilus influenzae type b and varicella vaccines. Despite very high final coverage, delayed vaccination was observed for hepatitis B (48.3% completed by 12 months). Significant delay was observed for the booster dose of pneumococcal conjugate vaccines (PCV) and meningococcal C conjugate vaccines (MCC). Of the total population studied, 82.3% received 3 PCV doses by 12 months, while 62.3% received the fourth dose by 24 months and 76.2% by 30 months. However, 89.6% received at least one MCC dose over 12 months. Timely vaccinated for hepatitis A with 2 doses by 24 months were 6.1%. Coverage was significantly low for Rotavirus (<20%) and influenza (23.1% one dose). High vaccination coverage is maintained for most vaccines at the beginning of the crisis in Greece. Coverage and timeliness show an increasing trend compared to previous studies. Sustained efforts are needed to support the preventive medicine system as socioeconomic instability continues. PMID- 27669157 TI - A Patient Registry to Improve Patient Safety: Recording General Neurosurgery Complications. AB - BACKGROUND: To improve the transparency of the local health care system, treatment cost was recently referenced to disease related groups. Treatment quality must be legally documented in a patient registry, in particular for the highly specialized treatments provided by neurosurgery departments. METHODS: In 2013 we have installed a patient registry focused on cranial neurosurgery. Surgeries are characterized by indication, treatment, location and other specific neurosurgical parameters. Preoperative state and postoperative outcome are recorded prospectively using neurological and sociological scales. Complications are graded by their severity in a therapy-oriented complication score system (Clavien-Dindo-Grading system, CDG). Results are presented at the monthly clinical staff meeting. RESULTS: Data acquisition compatible with the clinic workflow permitted to include all eligible patients into the registry. Until December 2015, we have registered 2880 patients that were treated in 3959 surgeries and 8528 consultations. Since the registry is fully operational (August 2014), we have registered 325 complications on 1341 patient discharge forms (24%). In 64% of these complications, no or only pharmacological treatment was required. At discharge, there was a clear correlation of the severity of the complication and the Karnofsky Performance Status (KPS, rho = -0.3, slope -6 KPS percentage points per increment of CDG) and the length of stay (rho = 0.4, slope 1.5 days per increment of CDG). CONCLUSIONS: While the therapy-oriented complication scores correlate reasonably well with outcome and length of stay, they do not account for new deficits that cannot be treated. Outcome grading and complication severity grading thus serve a complimentary purpose. Overall, the registry serves to streamline and to complete information flow in the clinic, to identify complication rates and trends early for the internal quality monitoring and communication with patients. Conversely, the registry influences clinical practice in that it demands rigorous documentation and standard operating procedures. PMID- 27669158 TI - TrpM, a Small Protein Modulating Tryptophan Biosynthesis and Morpho-Physiological Differentiation in Streptomyces coelicolor A3(2). AB - In the model actinomycete Streptomyces coelicolor A3(2), small open reading frames encoding proteins with unknown functions were identified in several amino acid biosynthetic gene operons, such as SCO2038 (trpX) in the tryptophan trpCXBA locus. In this study, the role of the corresponding protein in tryptophan biosynthesis was investigated by combining phenotypic and molecular analyses. The 2038KO mutant strain was characterized by delayed growth, smaller aerial hyphae and reduced production of spores and actinorhodin antibiotic, with respect to the WT strain. The capability of this mutant to grow on minimal medium was rescued by tryptophan and tryptophan precursor (serine and/or indole) supplementation on minimal medium and by gene complementation, revealing the essential role of this protein, here named TrpM, as modulator of tryptophan biosynthesis. His-tag pull down and bacterial adenylate cyclase-based two hybrid assays revealed TrpM interaction with a putative leucyl-aminopeptidase (PepA), highly conserved component among various Streptomyces spp. In silico analyses showed that PepA is involved in the metabolism of serine, glycine and cysteine through a network including GlyA, CysK and CysM enzymes. Proteomic experiments suggested a TrpM dependent regulation of metabolic pathways and cellular processes that includes enzymes such as GlyA, which is required for the biosynthesis of tryptophan precursors and key proteins participating in the morpho-physiological differentiation program. Altogether, these findings reveal that TrpM controls tryptophan biosynthesis at the level of direct precursor availability and, therefore, it is able to exert a crucial effect on the morpho-physiological differentiation program in S. coelicolor A3(2). PMID- 27669161 TI - Longitudinal pathways of sexual victimization, sexual self-esteem, and depression in women and men. AB - OBJECTIVE: This article presents a longitudinal analysis of the links between sexual assault victimization, depression, and sexual self-esteem by examining their cross-lagged paths among both men and women. METHOD: Male and female college students (N = 2,425) in Germany participated in the study that comprised 3 data waves in their first, second, and third year of university, separated by 12-month intervals. Sexual assault victimization was assessed at Time 1 (T1) since the age of 14 and at Time 2 (T2) and Time 3 (T3) for the last 12 months. Depression and sexual self-esteem were measured at each wave. RESULTS: Random intercept cross-lagged panel analyses, controlling for individual differences in depression and sexual self-esteem, showed that sexual assault at T1 predicted depression and lower sexual self-esteem at T2, and depression and lower self esteem at T2 predicted sexual assault victimization at T3. In addition, significant paths were found from T1 depression to T2 sexual assault victimization and from T2 sexual assault victimization to depression at T3. Sexual victimization at T1 was indirectly linked to sexual victimization at T3 via depression at T2. Both depression and sexual self-esteem at T1 were indirectly linked to sexual victimization at T3. The paths did not differ significantly between men and women. CONCLUSION: Sexual assault victimization was shown to be a risk factor for both depression as a general mental health indicator and lowered sexual self-esteem as a specific outcome in the domain of sexuality. Moreover, depression and sexual self-esteem increased the vulnerability for sexual assault victimization, which has implications for prevention and intervention efforts. (PsycINFO Database Record PMID- 27669160 TI - A Bayesian integrative approach for multi-platform genomic data: A kidney cancer case study. AB - Integration of genomic data from multiple platforms has the capability to increase precision, accuracy, and statistical power in the identification of prognostic biomarkers. A fundamental problem faced in many multi-platform studies is unbalanced sample sizes due to the inability to obtain measurements from all the platforms for all the patients in the study. We have developed a novel Bayesian approach that integrates multi-regression models to identify a small set of biomarkers that can accurately predict time-to-event outcomes. This method fully exploits the amount of available information across platforms and does not exclude any of the subjects from the analysis. Through simulations, we demonstrate the utility of our method and compare its performance to that of methods that do not borrow information across regression models. Motivated by The Cancer Genome Atlas kidney renal cell carcinoma dataset, our methodology provides novel insights missed by non-integrative models. PMID- 27669159 TI - Using a Control to Better Understand Phyllosphere Microbiota. AB - An important data gap in our understanding of the phyllosphere surrounds the origin of the many microbes described as phyllosphere communities. Most sampling in phyllosphere research has focused on the collection of microbiota without the use of a control, so the opportunity to determine which taxa are actually driven by the biology and physiology of plants as opposed to introduced by environmental forces has yet to be fully realized. To address this data gap, we used plastic plants as inanimate controls adjacent to live tomato plants (phyllosphere) in the field with the hope of distinguishing between bacterial microbiota that may be endemic to plants as opposed to introduced by environmental forces. Using 16S rRNA gene amplicons to study bacterial membership at four time points, we found that the vast majority of all species-level operational taxonomic units were shared at all time-points. Very few taxa were unique to phyllosphere samples. A higher taxonomic diversity was consistently observed in the control samples. The high level of shared taxonomy suggests that environmental forces likely play a very important role in the introduction of microbes to plant surfaces. The observation that very few taxa were unique to the plants compared to the number that were unique to controls was surprising and further suggests that a subset of environmentally introduced taxa thrive on plants. This finding has important implications for improving our approach to the description of core phytobiomes as well as potentially helping us better understand how foodborne pathogens may become associated with plant surfaces. PMID- 27669162 TI - A randomized trial of cognitive behavior therapy and cognitive therapy for children with posttraumatic stress disorder following single-incident trauma: Predictors and outcome at 1-year follow-up. AB - OBJECTIVE: The 1-year outcome and moderators of adjustment for children and youth receiving treatment for posttraumatic stress disorder (PTSD) following single incident trauma was examined. METHOD: Children and youth who had experienced single-incident trauma (N = 33; 7-17 years old) were randomly assigned to receive 9 weeks of either trauma-focused cognitive behavior therapy (CBT) or trauma focused cognitive therapy (without exposure; CT) that was administered to them and their parents individually. RESULTS: Intent-to-treat analyses demonstrated that both groups maintained posttreatment gains in PTSD, depression and general anxiety symptoms reductions at 1-year follow-up, with no children meeting criteria for PTSD. A large proportion of children showed good end-state functioning at follow-up (CBT: 65%; CT: 71%). Contrary to 6-month outcomes, maternal adjustment no longer moderated children's outcome, nor did any other tested variables. CONCLUSION: The findings confirm the positive longer-term outcomes of using trauma-focused cognitive-behavioral methods for PTSD secondary to single-incident trauma and that these outcomes are not dependent on the use of exposure. (PsycINFO Database Record PMID- 27669163 TI - Conceptual model of male military sexual trauma. AB - OBJECTIVE: Male sexual trauma is understudied, leaving much to be known about the unique mental health needs of male survivors. This study examined veteran men's perceptions of the effects of military sexual trauma. METHOD: Military sexual trauma was defined as physically forced, verbally coerced, or substance incapacitated acts experienced during military service. Interviews were conducted with 21 male veterans who reported experiencing military sexual trauma. Data were drawn together using a grounded theory methodology. RESULTS: Three categories emerged from data analysis, including (a) types of military sexual trauma (being touched in a sexual way against their will [N = 18]; sexual remarks directed at them [N = 15]; being physically forced to have sex [N = 13]); (b) negative life effects (difficulty trusting others [N = 18]; fear of abandonment [N = 17]; substance use [N = 13]; fear of interpersonal violence [N = 12]; conduct and vocational problems [N = 11]; irritability/aggression [N = 8]; insecurity about sexual performance [N = 8]; difficulty managing anger [N = 8]); and (c) posttraumatic growth (N = 15). CONCLUSIONS: Results from this study suggest sexual trauma in the military context may affect systems of self-organization, specifically problems in affective, self-concept, and relational domains, similar to symptoms of those who have experienced prolonged traumatic stressors. This model can be used by clinicians to select treatments that specifically target these symptoms and promote posttraumatic growth. (PsycINFO Database Record PMID- 27669164 TI - Mental disorders among Chernobyl cleanup workers from Estonia: A clinical assessment. AB - OBJECTIVE: To assess, at a clinical level, the mental health of former Chernobyl cleanup workers from Estonia by comparing them with same-age controls. METHOD: The Mini International Neuropsychiatric Interview (MINI) was administered during 2011-2012 to 99 cleanup workers and 100 population-based controls previously screened for mental health symptoms. RESULTS: Logistic regression analysis showed that cleanup workers had higher odds of current depressive disorder (odds ratio [OR] = 3.07, 95% confidence interval [CI: 1.34, 7.01]), alcohol dependence (OR = 3.47, 95% CI [1.29, 9.34]), and suicide ideation (OR = 3.44, 95% CI [1.28, 9.21]) than did controls. Except for suicide ideation, associations with Chernobyl exposure became statistically nonsignificant when adjusted for education and ethnicity. CONCLUSION: A quarter of a century after the Chernobyl accident, Estonian cleanup workers were still at increased risk of mental disorders, which was partly attributable to sociodemographic factors. (PsycINFO Database Record PMID- 27669166 TI - Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction. AB - Optimization of a protein's pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability, and biosynthesis potential and reduced inhibition by anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence. PMID- 27669165 TI - Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling. AB - Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes, and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized. We present a multi-omic data analysis and visualization tool that we use to find covariance networks that can predict molecular functions, correlations between profiles of related gene deletions, gene-specific perturbations that reflect protein functions, and a global respiration deficiency response. Using this multi-omic approach, we link seven proteins including Hfd1p and its human homolog ALDH3A1 to mitochondrial coenzyme Q (CoQ) biosynthesis, an essential pathway disrupted in many human diseases. This Resource should provide molecular insights into mitochondrial protein functions. PMID- 27669167 TI - Modeling of RNA-seq fragment sequence bias reduces systematic errors in transcript abundance estimation. AB - We find that current computational methods for estimating transcript abundance from RNA-seq data can lead to hundreds of false-positive results. We show that these systematic errors stem largely from a failure to model fragment GC content bias. Sample-specific biases associated with fragment sequence features lead to misidentification of transcript isoforms. We introduce alpine, a method for estimating sample-specific bias-corrected transcript abundance. By incorporating fragment sequence features, alpine greatly increases the accuracy of transcript abundance estimates, enabling a fourfold reduction in the number of false positives for reported changes in expression compared with Cufflinks. Using simulated data, we also show that alpine retains the ability to discover true positives, similar to other approaches. The method is available as an R/Bioconductor package that includes data visualization tools useful for bias discovery. PMID- 27669168 TI - Tailoring Complex Care Management for High-Need, High-Cost Patients. PMID- 27669171 TI - Reactive oxygen species contribute toward Smac mimetic/temozolomide-induced cell death in glioblastoma cells. AB - Small-molecule inhibitors of Inhibitor of Apoptosis proteins such as Smac mimetics have been reported to provide a promising tool to sensitize glioblastoma (GBM) cells to cytotoxic therapies including chemotherapeutic drugs. However, the underlying molecular mechanisms of action have not yet been fully unraveled. In the present study, we therefore investigated the role of reactive oxygen species (ROS) in the regulation of Smac mimetic/temozolomide (TMZ)-induced cell death in GBM cells. Here, we show that the Smac mimetic BV6 and TMZ act in concert to stimulate the production of both cytosolic and mitochondrial ROS. This accumulation of ROS contributes toward the activation of the proapoptotic factor BAX upon BV6/TMZ cotreatment as several ROS scavengers (i.e. N-acetyl-L-cysteine, MnTBAP, or alpha-tocopherol) protect GBM cells against BV6/TMZ-mediated BAX activation. In addition, ROS scavengers significantly rescue GBM cells from BV6/TMZ-triggered cell death, indicating that ROS generation is required for the induction of cell death. By showing that ROS play an important role in the regulation of Smac mimetic/TMZ-induced cell death, our work sheds light on the crucial role of the oxidative system in the cooperative antitumor activity of Smac mimetic/TMZ combination therapy against GBM cells. PMID- 27669170 TI - Spatial Variations in Dengue Transmission in Schools in Thailand. AB - BACKGROUND: Dengue is an important neglected tropical disease, with more than half of the world's population living in dengue endemic areas. Good understanding of dengue transmission sites is a critical factor to implement effective vector control measures. METHODS: A cohort of 1,811 students from 10 schools in rural, semi-rural and semi-urban Thailand participated in this study. Seroconversion data and location of participants' residences and schools were recorded to determine spatial patterns of dengue infections. Blood samples were taken to confirm dengue infections in participants at the beginning and the end of school term. Entomological factors included a survey of adult mosquito density using a portable vacuum aspirator during the school term and a follow up survey of breeding sites of Aedes vectors in schools after the school term. Clustering analyses were performed to detect spatial aggregation of dengue infections among participants. RESULTS: A total of 57 dengue seroconversions were detected among the 1,655 participants who provided paired blood samples. Of the 57 confirmed dengue infections, 23 (40.0%) occurred in students from 6 (6.8%) of the 88 classrooms in 10 schools. Dengue infections did not show significant clustering by residential location in the study area. During the school term, a total of 66 Aedes aegypti mosquitoes were identified from the 278 mosquitoes caught in 50 classrooms of the 10 schools. In a follow-up survey of breeding sites, 484 out of 2,399 water containers surveyed (20.2%) were identified as active mosquito breeding sites. DISCUSSION AND CONCLUSION: Our findings suggest that dengue infections were clustered among schools and among classrooms within schools. The schools studied were found to contain a large number of different types of breeding sites. Aedes vector densities in schools were correlated with dengue infections and breeding sites in those schools. Given that only a small proportion of breeding sites in the schools were subjected to vector control measures (11%), this study emphasizes the urgent need to implement vector control strategies at schools, while maintaining efforts at the household level. PMID- 27669169 TI - Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Patients Treated with First-Line Tyrosine Kinase Inhibitors. AB - RATIONALE: Patients with non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR) are relatively sensitive to EGFR-tyrosine kinase inhibitor (TKI) treatment and have longer progression-free survival (PFS) when treated with EGFR-TKI compared with platinum-based chemotherapy. However, many patients with advanced NSCLC who have mutated EGFR do not respond to first line EGFR-TKI treatment and still have shorter PFS. OBJECTIVES: The aim of this study was to identify genetic variants associated with PFS among patients with lung adenocarcinoma who were treated with first-line EGFR-TKIs. METHODS: A genome wide association study on PFS was performed in never-smoking women diagnosed with lung adenocarcinoma and who were treated with first-line EGFR-TKIs (n = 128). Significant single-nucleotide polymorphisms (SNPs) were selected for follow-up association analysis (n = 198) and for replication assay in another independent cohort (n = 153). MEASUREMENTS AND MAIN RESULTS: We identified SNPs at 4q12 associated with PFS at genome-wide significance (P < 10-8) and with an estimated hazard ratio of more than 4. This association was also replicated in a larger but similar cohort and in an independent NSCLC cohort. Follow-up functional analyses showed that these SNPs were associated with the expression of EGFR, which encodes the TKI target, and with a nearby gene neuromedin-U, which encodes a G protein coupled receptor ligand known to be involved in the progression of NSCLC. Considering these as possible prognostic biomarkers for the treatment of patients with late-stage lung cancer, we found that these SNPs were not associated with EGFR mutation status or with polymorphism of the Bcl2-interacting mediator of cell death gene. CONCLUSIONS: Genetic variants in 4q12 merit further investigation to assess their potential as pharmacogenomic predictors for and to understand the biology underlying its influence on PFS in patients treated with TKI therapy. PMID- 27669172 TI - UNC119 mediates gambogic acid-induced cell-cycle dysregulation through the Gsk3beta/beta-catenin pathway in hepatocellular carcinoma cells. AB - UNC119 (uncoordinated 119 or retinal protein 4), specifically expressed in the photoreceptors in the retina, has recently been found to be upregulated in hepatocellular carcinoma (HCC) tissues, predicting a poor prognosis. However, the biological role of UNC119 in cancer treatment is still poorly understood. Gambogic acid (GA), a major component of gambogic resin, has been shown to possess anticancer activity against multiple human cancer cell lines. In the present study, we discovered that GA was more effective in inhibiting cell proliferation in HCC cells with a higher level of UNC119. In addition, GA inhibited UNC119 expression and induced Hep3B cells G0/G1 arrest. Cell-cycle related proteins, such as cyclin A, E, D1, and p-cyclin-dependent kinase 2, 4, 6 were downregulated in GA-treated cells. Glycogen synthase kinase 3beta (Gsk3beta)/beta-catenin signaling, the downstream of UNC119, was also found to be suppressed after GA treatment. UNC119 knockdown or over expression experiment further proved that UNC119 mediated the effect of GA on the HCC cell cycle and Gsk3beta/beta-catenin signaling. In BALB/c mice bearing xenotransplanted tumors, the growth of the Hep3B tumor was inhibited by GA treatment. Immunohistochemistry results of tumor tissues suggested that GA might also exert its anticancer effect by inhibiting UNC119 and regulating cell cycle in vivo. Thus, GA could be a potential therapeutic agent in the treatment of human HCC. PMID- 27669173 TI - Dietary Enrichment with 20% Fish Oil Decreases Mucus Production and the Inflammatory Response in Mice with Ovalbumin-Induced Allergic Lung Inflammation. AB - The prevalence of asthma has increased in recent decades, which may be related to higher dietary intake of (n-6) polyunsaturated fatty acids (PUFA) and lower intake of (n-3) PUFA, e.g., those contained in fish oil. The objective of this study was to determine if dietary PUFA enrichment decreases mucus production or the inflammatory response associated with ovalbumin (OVA)-induced allergic lung inflammation. Mice (n = 10/group) were fed control, 20% fish oil, or 20% corn oil enriched diets for a total of 12 weeks. At 8 and 10 weeks, mice were given an intraperitoneal injection of saline (10 control-fed mice) or OVA (30 remaining mice). Once at 10 weeks and on 3 consecutive days during week 12, mice were challenged by nebulizing with saline or OVA. Mice were euthanized 24 hours after the last challenge and blood was collected for plasma FA analysis. Bronchoalveolar lavage (BAL) fluid was collected to determine cell composition and Th2-type cytokine (IL-4, IL-13) concentrations. Periodic acid-Schiff (PAS) + mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue were quantified using morphometric analysis. Relative abundance of mRNA for mucin (Muc4, Muc5ac, and Muc5b) and Th2-type cytokine (IL-4, IL-5, and IL-13) genes were compared with beta-actin by qPCR. Supplementation with either corn oil or fish oil effectively altered plasma FA profiles towards more (n-6) FA or (n-3) FA, respectively (P < 0.0001). Sensitization and challenge with OVA increased the proportion of neutrophils, lymphocytes, and eosinophils, and decreased the proportion of macrophages and concentrations of IL-13 in BAL fluid; increased the percentage of PAS+ mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue; and increased gene expression of mucins (Muc4, Muc5ac, and Muc5b) and Th2-type cytokines (IL-5 and IL-13) in lung tissue of control-fed mice. Dietary PUFA reversed the increase in PAS+ mucus-producing cells (P = 0.003). In addition, dietary enrichment with fish oil attenuated the percentage of CD45+ inflammatory cell infiltrates in lung tissue, and increased Muc4 and Muc 5b gene expression compared with OVA-sensitized and challenged control mice. In conclusion, dietary enrichment with either (n-3) or (n-6) PUFA decreased mucus production in lung tissues of OVA-sensitized and challenged mice. More specifically, enrichment with dietary (n-3) PUFA decreased CD45+ inflammatory cell infiltrates, thus inducing potentially beneficial changes in lung tissue of OVA-sensitized and challenged mice. PMID- 27669174 TI - Short article: Buried bumper syndrome in children: incidence and risk factors. AB - OBJECTIVE: Buried bumper syndrome (BBS) is a serious complication in gastrostomy dependent children. Many need surgical correction. On account of comorbidities, this becomes a high-risk procedure. Our aim was to review the incidence of BBS in children and to identify the risk factors. PATIENTS AND METHODS: Retrospective review of patients' records over 10 years, 2006-2015, was carried out. Types of tubes, operative interventions, comorbidities and records were noted. Two-tailed Fisher's exact test was used for statistical analysis. RESULTS: A total of 535 patients were reviewed. Overall, 475 had only percutaneous endoscopic gastrostomy (PEG) and 60 had a jejunal extension with percutaneous endoscopic gastrostomy (PEG-J). Twenty-nine patients (PEG-J - 16/26; PEG - 13/26) had a total of 31 BBS episodes. The overall incidence of BBS in our study was 5.4%. The age at presentation ranged from 1 to 18 years (median 8.6 years). All had significant comorbidities (neurodevelopmental 26/29, cardiorespiratory 14/29, genetic 16/29). Overall, 27/29 had two or more comorbidities. The mean time to development of BBS was 1025+/-634 days. BBS was found in the second or the subsequent tube in four patients with PEGs (P<0.0004) and in 10 PEG-Js (P<0.0001). Twenty-five patients needed laparotomy. There were no postoperative deaths. CONCLUSION: In BBS, the two significant risk factors identified were a having PEG-J and two or more previous gastrostomy insertions. Vigilance in documentation and prolonged follow up to provide regular education to carers can reduce the incidence of this preventable complication. PMID- 27669175 TI - Efficacy of prophylactic antiviral therapy and outcomes in HBsAg-negative, anti HBc-positive patients receiving chemotherapy: a real-life experience. AB - OBJECTIVE: The aim of this study is to evaluate the outcomes of hepatitis B surface antigen (HBsAg)-negative, anti-HBc-positive patients who received immunosuppressive therapies. PATIENTS AND METHODS: We retrospectively evaluated the medical records of HBsAg-negative, anti-HBc-positive patients with hematological diseases or solid tumors who underwent immunosuppressive therapies and were referred because of positive baseline hepatitis B virus (HBV) serology or HBV reactivation. The referral date was according to the judgment of the treating physician at the time of identification of any signs of HBV infection. RESULTS: We included 55 HBsAg-negative, anti-HBc-positive patients. Of these, 31 received antiviral prophylaxis (group 1), whereas 24 patients did not receive any anti-HBV agent (group 2). The majority of patients [49/55 (89%)] had hematological malignancies and most of them 39/55 (71%) received rituximab containing regimens. Lamivudine was used as antiviral prophylaxis in 13/31 (42%) patients of group 1. One patient in this group experienced HBV reactivation and was treated successfully with tenofovir add-on therapy. All patients in the second group experienced HBV reactivation and most of them [19/24 (79%)] were treated with tenofovir or entecavir as rescue therapy. Two of these patients (one of the tenofovir/entecavir subgroup and one of the lamivudine subgroup) eventually died because of hepatic failure despite rescue treatment. CONCLUSION: Patients with serological markers of previous HBV infection are still at risk for HBV reactivation. Screening of both anti-HBs and anti-HBc is mandatory before chemotherapy. Pre-emptive antiviral prophylaxis, including lamivudine, is highly effective in all subgroups of such patients, whereas deferring treatment upon HBV reactivation is not enough to rescue all cases. PMID- 27669176 TI - Relative validity of a web-based food frequency questionnaire for patients with type 1 and type 2 diabetes in Denmark. AB - BACKGROUND: Diet has an important role in the management of diabetes. However, little is known about dietary intake in Danish diabetes patients. A food frequency questionnaire (FFQ) focusing on most relevant nutrients in diabetes including carbohydrates, dietary fibres and simple sugars was developed and validated. OBJECTIVES: To examine the relative validity of nutrients calculated by a web-based food frequency questionnaire for patients with diabetes. DESIGN: The FFQ was validated against a 4-day pre-coded food diary (FD). Intakes of nutrients were calculated. Means of intake were compared and cross classifications of individuals according to intake were performed. To assess the agreement between the two methods, Pearson and Spearman's correlation coefficients and weighted kappa coefficients were calculated. SUBJECTS: Ninety patients (64 with type 1 diabetes and 26 with type 2 diabetes) accepted to participate in the study. Twenty-six were excluded from the final study population. SETTING: 64 volunteer diabetes patients at the Steno Diabetes Center. RESULTS: Intakes of carbohydrates, simple sugars, dietary fibres and total energy were higher according to the FFQ compared with the FD. However, intakes of nutrients were grossly classified in the same or adjacent quartiles with an average of 82% of the selected nutrients when comparing the two methods. In general, moderate agreement between the two methods was found. CONCLUSION: The FFQ was validated for assessment of a range of nutrients. Comparing the intakes of selected nutrients (carbohydrates, dietary fibres and simple sugars), patients were classified correctly according to low and high intakes. The FFQ is a reliable dietary assessment tool to use in research and evaluation of patient education for patients with diabetes. PMID- 27669177 TI - Situational cues and momentary food environment predict everyday eating behavior in adults with overweight and obesity. AB - OBJECTIVES: Individual eating behavior is a risk factor for obesity and highly dependent on internal and external cues. Many studies also suggest that the food environment (i.e., food outlets) influences eating behavior. This study therefore examines the momentary food environment (at the time of eating) and the role of cues simultaneously in predicting everyday eating behavior in adults with overweight and obesity. METHOD: Intensive longitudinal study using ecological momentary assessment (EMA) over 14 days in 51 adults with overweight and obesity (average body mass index = 30.77; SD = 4.85) with a total of 745 participant days of data. Multiple daily assessments of eating (meals, high- or low-energy snacks) and randomly timed assessments. Cues and the momentary food environment were assessed during both assessment types. RESULTS: Random effects multinomial logistic regression shows that both internal (affect) and external (food availability, social situation, observing others eat) cues were associated with increased likelihood of eating. The momentary food environment predicted meals and snacking on top of cues, with a higher likelihood of high-energy snacks when fast food restaurants were close by (odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.22, 2.93) and a higher likelihood of low-energy snacks in proximity to supermarkets (OR = 2.29, 95% CI = 1.38, 3.82). CONCLUSIONS: Real time eating behavior, both in terms of main meals and snacks, is associated with internal and external cues in adults with overweight and obesity. In addition, perceptions of the momentary food environment influence eating choices, emphasizing the importance of an integrated perspective on eating behavior and obesity prevention. (PsycINFO Database Record PMID- 27669178 TI - Social support and physical activity change in Latinas: Results from the Seamos Saludables trial. AB - OBJECTIVE: Family responsibilities and poor social support are barriers to physical activity among Latinas. This study evaluated the effects of a home- and print-based intervention on social support, moderating effects of familial ties on support and moderate-to-vigorous physical activity (MVPA), and mediating effects of support on MVPA. METHOD: Participants were randomized to receive through the mail either individually tailored physical activity intervention or general wellness print materials. Familial ties and social support were assessed by marital and child status and the social support for physical activity measure, respectively. MVPA was measured using the 7-day Physical Activity Recall Interview and accelerometer. Assessments were conducted at baseline, 6 months posttreatment, and 12 months follow-up. RESULTS: Participants (n = 266; 40.6 +/- 9.9 years old) were mostly immigrant and Spanish-speaking Latinas. The intervention group achieved greater increases in family and friend support compared to the wellness control group from baseline to posttreatment and follow up (p < .05). Intervention changes in support did not depend on marital or child status. The intervention also increased minutes per week of MVPA more than the wellness control (p < .05) and the effect did not depend on marital or child status. There were significant indirect effects of treatment, indicating the intervention achieved greater increases in MVPA by increasing family (ab = 5.21, SE = 2.94, 95% confidence interval [CI] = 0.91-14.11) and friend (ab = 6.83, SE = 5.15, 95% CI = 0.16-20.56) support. CONCLUSIONS: The intervention improved and sustained support from family and friends and MVPA irrespective of familial ties. Social support mediated increases in MVPA. (PsycINFO Database Record PMID- 27669182 TI - Mechanical Demands of the Hang Power Clean and Jump Shrug: A Joint-Level Perspective. AB - Kipp, K, Malloy, PJ, Smith, J, Giordanelli, MD, Kiely, MT, Geiser, CF, and Suchomel, TJ. Mechanical demands of the hang power clean and jump shrug: a joint level perspective. J Strength Cond Res 32(2): 466-474, 2018-The purpose of this study was to investigate the joint- and load-dependent changes in the mechanical demands of the lower extremity joints during the hang power clean (HPC) and the jump shrug (JS). Fifteen male lacrosse players were recruited from a National Collegiate Athletic Association DI team, and completed 3 sets of the HPC and JS at 30, 50, and 70% of their HPC 1 repetition maximum (1RM HPC) in a counterbalanced and randomized order. Motion analysis and force plate technology were used to calculate the positive work, propulsive phase duration, and peak concentric power at the hip, knee, and ankle joints. Separate 3-way analysis of variances were used to determine the interaction and main effects of joint, load, and lift type on the 3 dependent variables. The results indicated that the mechanics during the HPC and JS exhibit joint-, load-, and lift-dependent behavior. When averaged across joints, the positive work during both lifts increased progressively with external load, but was greater during the JS at 30 and 50% of 1RM HPC than during the HPC. The JS was also characterized by greater hip and knee work when averaged across loads. The joint-averaged propulsive phase duration was lower at 30% than at 50 and 70% of 1RM HPC for both lifts. Furthermore, the load-averaged propulsive phase duration was greater for the hip than the knee and ankle joint. The joint-averaged peak concentric power was the greatest at 70% of 1RM for the HPC and at 30%-50% of 1RM for the JS. In addition, the joint-averaged peak concentric power of the JS was greater than that of the HPC. Furthermore, the load-averaged peak knee and ankle concentric joint powers were greater during the execution of the JS than the HPC. However, the load averaged power of all joints differed only during the HPC, but was similar between the hip and knee joints for the JS. Collectively, these results indicate that compared with the HPC the JS is characterized by greater hip and knee positive joint work, and greater knee and ankle peak concentric joint power, especially if performed at 30 and 50% of 1RM HPC. This study provides important novel information about the mechanical demands of 2 commonly used exercises and should be considered in the design of resistance training programs that aim to improve the explosiveness of the lower extremity joints. PMID- 27669179 TI - The impact of stress at different life stages on physical health and the buffering effects of maternal sensitivity. AB - OBJECTIVE: Many studies indicate that early life stress leads to negative health outcomes in adulthood, and some suggest that high-quality parenting might buffer these effects. Most prior research, however, has relied on cross-sectional retrospective reports of stress and parenting. Our study tests how coder-rated stress and parenting quality assessed at different life stages predict adult health outcomes in a prospective, longitudinal study. METHOD: Participants were 163 individuals in the Minnesota Longitudinal Study of Risk and Adaptation studied since birth. Physical health was assessed at age 32 with body mass index, self-reports of symptoms and illnesses experienced, and self-ratings of overall physical health. Stress was assessed by coder-rated interviews involving participants or their mothers at 16 time points partitioned into 5 life stages: early childhood, middle childhood, adolescence, young adulthood, and at age 32 (when health was assessed). Parenting quality was measured by coder ratings of each mother's provision of sensitive, responsive support at 7 time points between birth and age 13. RESULTS: Early childhood, adolescent, and concurrent stress predicted adult health outcomes at age 32. Early childhood and adolescent stress, and adolescent and concurrent stress, both showed a "dual-risk" pattern, such that experiencing higher stress at both of these life stages predicted the worst health outcomes. Higher maternal sensitivity, however, buffered these deleterious effects. CONCLUSION: Our prospective data reveal that early childhood and adolescence are important developmental periods during which stress is influential for adult physical health. However, parenting interventions that promote greater sensitivity may help children in high-stress environments avoid negative adult health outcomes. (PsycINFO Database Record PMID- 27669186 TI - The Perceived Psychological Responsibilities of a Strength and Conditioning Coach. AB - Radcliffe, JN, Comfort, P, and Fawcett, T. The perceived psychological responsibilities of a strength and conditioning coach. J Strength Cond Res 32(10): 2853-2862, 2016-Research is limited in exploring the specific psychology oriented responsibilities of the strength and conditioning professional. The present research explored the psychological responsibilities adopted by accredited strength and conditioning coaches. Participants comprised 10 coaches working within the United Kingdom, 3 within the United States, and 5 within Australia offering a cross-section of experience from various sport disciplines and educational backgrounds. Participants were interviewed either in person or via Skype. Thematic clustering was followed using interpretative phonological analysis to identify common themes. Over half (61%) of the respondents reported that their position as a strength and conditioning coach required additional psychology-oriented responsibilities. These comprised a counseling role in the absence of a psychologist and the use of "softer skills" in a mentoring role to the athlete during a challenging situation. The coach could play an influential role in shaping the mentality of the team. The coach identifies how the role results in working to relay information from the athlete to other support staff and similarly from the support staff to the athlete. In addition to identifying the resonant psychology-oriented responsibilities, discussion is made with specific focus on the ethical boundary within which strength and conditioning coaches must reside regarding the competencies to provide psychological support. PMID- 27669187 TI - Muscle-Specific Effective Mechanical Advantage and Joint Impulse in Weightlifting. AB - Kipp, K, and Harris, C. Muscle-specific effective mechanical advantage and joint impulse in weightlifting. J Strength Cond Res 31(7): 1905-1910, 2017-Lifting greater loads during weightlifting exercises may theoretically be achieved through increasing the magnitudes of net joint impulses or manipulating the joints' effective mechanical advantage (EMA). The purpose of this study was to investigate muscle-specific EMA and joint impulse as well as impulse-momentum characteristics of the lifter-barbell system across a range of external loads during the execution of the clean. Collegiate-level weightlifters performed submaximal cleans at 65, 75, and 85% of their 1-repetition maximum (1-RM), whereas data from a motion analysis system and a force plate were used to calculate lifter-barbell system impulse and velocity, as well as net extensor impulse generated at the hip, knee, and ankle joints and the EMA of the gluteus maximus, hamstrings, quadriceps, and triceps surae muscles. The results indicated that the lifter-barbell system impulse did not change as load increased, whereas the velocity of the lifter-barbell system decreased with greater load. In addition, the net extensor impulse at all joints increased as load increased. The EMA of all muscles did not, however, change as load increased. The load-dependent effects on the impulse-velocity characteristics of the lifter-barbell system may reflect musculoskeletal force-velocity behaviors, and may further indicate that the weightlifting performance is limited by the magnitude of ground reaction force impulse. In turn, the load-dependent effects observed at the joint level indicated that lifting greater loads were due to greater net extensor impulses generated at the joints of the lower extremity and not greater EMAs of the respective extensor muscles. In combination, these results suggest that lifting greater external loads during the clean is due to the ability to generate large extensor joint impulses, rather than manipulate EMA. PMID- 27669188 TI - Influence of Competition Day on Cognitive Control and HRV in Young Male Gymnasts. AB - Sartor, F, Capuzzoni, S, Rospo, G, La Torre, A, Vailati, F, and Vailati, E. Influence of competition day on cognitive control and HRV in young male gymnasts. J Strength Cond Res 31(7): 1982-1993, 2017-In gymnastics, high levels of executive attention and physical and coordinative capacities are required. However, training planning does not usually account for dynamic alterations in cognitive capacity. This study investigated whether cognitive capacity was altered by the approach of a competition. Ten elite male gymnasts (16 +/- 2 years, 57.3 +/- 16.1 kg, 1.64 +/- 1.27 m) were monitored for sleep, life demands, rating of perceived exertion (RPE), and pain, starting 5 days before the competition and up to 5 days after it. Stroop task performance and concomitant heart rate variability (HRV) were monitored 5 days and 1 day before the competition and then 1 and 5 days after. Sleep and life demands were not affected by the competition. Localized pain ranged from mild to moderate levels throughout the observation period. It weakly correlated with RPE (r = 0.241, p = 0.010) and moderately with number of errors (NoEs) (r = 0.639, p = 0.047). The RPE was higher for the competition day (p = 0.002). Median reaction times during the Stroop task were higher in the period preceding the competition (p < 0.001) for similar NoEs. The HRV during the congruent stimuli task showed higher root mean square differences of successive beats, portion of normal to normal intervals exceeding 50 milliseconds, and high frequency after the competition (p <= 0.05). Poincare plot SD2 showed a positive correlation with Stroop task NoEs (r = 0.590, p < 0.001). In conclusion, the period preceding an important competition affected cognitive performance and HRV in young male gymnasts. A practical implication of this study is that training loads could be adjusted according to mental stress before a competition. PMID- 27669189 TI - Maximal Strength Performance and Muscle Activation for the Bench Press and Triceps Extension Exercises Adopting Dumbbell, Barbell, and Machine Modalities Over Multiple Sets. AB - Farias, DdA, Willardson, JM, Paz, GA, Bezerra, EdS, and Miranda, H. Maximal strength performance and muscle activation for the bench press and triceps extension exercises adopting dumbbell, barbell and machine modalities over multiple sets. J Strength Cond Res 31(7): 1879-1887, 2017-The purpose of this study was to investigate muscle activation, total repetitions, and training volume for 3 bench press (BP) exercise modes (Smith machine [SMBP], barbell [BBP], and dumbbell [DBP]) that were followed by a triceps extension (TE) exercise. Nineteen trained men performed 3 testing protocols in random order, which included: (P1) SMBP + TE; (P2) BBP + TE; and (P3) DBP + TE. Each protocol involved 4 sets with a 10-repetition maximum (RM) load, immediately followed by a TE exercise that was also performed for 4 sets with a 10RM load. A 2-minute rest interval was adopted between sets and exercises. Surface electromyographic activity was assessed for the pectoralis major (PM), anterior deltoid (AD), biceps brachii (BB), and triceps brachii (TB). The results indicated that significantly higher total repetitions were achieved for the DBP (31.2 +/- 3.2) vs. the BBP (27.8 +/- 4.8). For the TE, significantly greater volume was achieved when this exercise was performed after the BBP (1,204.4 +/- 249.4 kg) and DBP (1,216.8 +/- 287.5 kg) vs. the SMBP (1,097.5 +/- 193 kg). The DBP elicited significantly greater PM activity vs. the BBP. The SMBP elicited significantly greater AD activity vs. the BBP and DBP. During the different BP modes, the SMBP and BBP elicited significantly greater TB activity vs. the DBP. However, the DBP elicited significantly greater BB activity vs. the SMBP and BBP, respectively. During the succeeding TE exercise, significantly greater activity of the TB was observed when this exercise was performed after the BBP vs. the SMBP and DBP. Therefore, it seems that the variation in BP modes does influence both repetition performance and muscle activation patterns during the TE when these exercises are performed in succession. PMID- 27669191 TI - Influence of Physical Maturity Status on Sprinting Speed Among Youth Soccer Players. AB - McCunn, R, Weston, M, Hill, JKA, Johnston, RD, and Gibson, NV. Influence of physical maturity status on sprinting speed among youth soccer players. J Strength Cond Res 31(7): 1795-1801, 2017-The relative age effect is well documented with the maturation-selection hypothesis the most common explanation; however, conflicting evidence exists. We observed the birth date distribution within an elite junior soccer academy. The influence of physical maturity status on anthropometric variables and sprinting ability was also investigated. Annual fitness testing was conducted over an 8-year period with a total of 306 players (age: 12.5 +/- 1.7 years [range: 9.7-16.6 years]; stature: 156.9 +/- 12.9 cm; mass: 46.5 +/- 12.5 kg) drawn from 6 age categories (under-11s to under-17s) who attended the same Scottish Premiership club academy. Measurements included mass, stature, maturity offset and 0-15 m sprint. Odds ratios revealed a clear bias toward recruitment of players born in quartile 1 compared with quartile 4. The overall effect (all squads combined) of birth quartile was very likely small for maturity offset (0.85 years; 90% confidence interval [CI], 0.44-1.26 years) and stature (6.2 cm; 90% CI, 2.8-9.6 cm), and likely small for mass (5.1 kg; 90% CI, 1.7-8.4 kg). The magnitude of the relationship between maturity offset and 15-m sprinting speed ranged from trivial for under-11s (r = 0.01; 90% CI, -0.14 to 0.16) to very likely large for under-15s (r = -0.62; -0.71 to -0.51). Making decisions about which players to retain and release should not be based on sprinting ability around the under-14 and under-15 age categories because any interindividual differences may be confounded by transient inequalities in maturity offset. PMID- 27669192 TI - Reliability and Validity of the Load-Velocity Relationship to Predict the 1RM Back Squat. AB - Banyard, HG, Nosaka, K, and Haff, GG. Reliability and validity of the load velocity relationship to predict the 1RM back squat. J Strength Cond Res 31(7): 1897-1904, 2017-This study investigated the reliability and validity of the load velocity relationship to predict the free-weight back squat one repetition maximum (1RM). Seventeen strength-trained males performed three 1RM assessments on 3 separate days. All repetitions were performed to full depth with maximal concentric effort. Predicted 1RMs were calculated by entering the mean concentric velocity of the 1RM (V1RM) into an individualized linear regression equation, which was derived from the load-velocity relationship of 3 (20, 40, 60% of 1RM), 4 (20, 40, 60, 80% of 1RM), or 5 (20, 40, 60, 80, 90% of 1RM) incremental warm-up sets. The actual 1RM (140.3 +/- 27.2 kg) was very stable between 3 trials (ICC = 0.99; SEM = 2.9 kg; CV = 2.1%; ES = 0.11). Predicted 1RM from 5 warm-up sets up to and including 90% of 1RM was the most reliable (ICC = 0.92; SEM = 8.6 kg; CV = 5.7%; ES = -0.02) and valid (r = 0.93; SEE = 10.6 kg; CV = 7.4%; ES = 0.71) of the predicted 1RM methods. However, all predicted 1RMs were significantly different (p <= 0.05; ES = 0.71-1.04) from the actual 1RM. Individual variation for the actual 1RM was small between trials ranging from -5.6 to 4.8% compared with the most accurate predictive method up to 90% of 1RM, which was more variable (-5.5 to 27.8%). Importantly, the V1RM (0.24 +/- 0.06 m.s) was unreliable between trials (ICC = 0.42; SEM = 0.05 m.s; CV = 22.5%; ES = 0.14). The load-velocity relationship for the full depth free-weight back squat showed moderate reliability and validity but could not accurately predict 1RM, which was stable between trials. Thus, the load-velocity relationship 1RM prediction method used in this study cannot accurately modify sessional training loads because of large V1RM variability. PMID- 27669193 TI - Validity of Selected Bioimpedance Equations for Estimating Body Composition in Men and Women: A Four-Compartment Model Comparison. AB - Nickerson, BS, Esco, MR, Bishop, PA, Schumacker, RE, Richardson, MT, Fedewa, MV, Wingo, JE, and Welborn, BA. Validity of selected bioimpedance equations for estimating body composition in men and women: a four-compartment model comparison. J Strength Cond Res 31(7): 1963-1972, 2017-The purpose of this study was to compare body fat percentage (BF%) and fat-free mass (FFM) values from bioelectrical impedance analysis (BIA) equations to values determined from a 4 compartment (4C) model. Eighty-two adults (42 men and 40 women) volunteered to participate (age = 23 +/- 5 years). Body fat percentage and FFM were estimated from previously developed BIA equations by Chumlea et al. (BIACH), Deurenberg et al. (BIADE), Kyle et al. (BIAKYLE), and Sun et al. (BIASUN). Four-compartment model body composition was derived from underwater weighing for body density, dual-energy X-ray absorptiometry for bone mineral content, and bioimpedance spectroscopy for total body water. The standard error of estimate (SEE) for group BF% and FFM ranged from 3.0 to 3.8% and 2.1 to 2.7 kg, respectively. The constant error (CE) was significantly higher and lower for BF% and FFM (p < 0.001), respectively, for 3 BIA equations (BIACH, CE = 3.1% and -2.2 kg; BIADE, CE = 3.7% and -2.9 kg; BIAKYLE, CE = 2.3% and -1.9 kg), but was not significant for BF% (p = 0.702) and FFM (p = 0.677) for BIASUN (CE = -0.1% and 0.1 kg). The 95% limits of agreement were narrowest for BIACH (+/-5.9%; +/-4.2 kg) and largest for BIADE (+/-7.4%; +/-6.2 kg). The significant CE yielded by BIACH, BIADE, and BIAKYLE indicates these equations tend to overpredict group BF% and underestimate group FFM. However, all BIA equations produced low SEEs and fairly narrow limits of agreement. When the use of a 4C model is not available, practitioners might consider using one of the selected BIA equations, but should consider the associated CE. PMID- 27669194 TI - Vertical and Horizontal Impact Force Comparison During Jump Landings With and Without Rotation in NCAA Division I Male Soccer Players. AB - Harry, JR, Barker, LA, Mercer, JA, and Dufek, JS. Vertical and horizontal impact force comparison during jump landings with and without rotation in NCAA Division I male soccer players. J Strength Cond Res 31(7): 1780-1786, 2017-There is a wealth of research on impact force characteristics when landing from a jump. However, there are no data on impact forces during landing from a jump with an airborne rotation about the vertical axis. We examined impact force parameters in the vertical and horizontal axes during vertical jump (VJ) landings and VJ landings with a 180 degrees rotation (VJR). Twenty-four Division I male soccer players performed 3 VJ and VJR landings on a dual-force platform system. Paired samples t-tests (alpha = 0.05) compared differences in the first (F1) and second (F2) peak vertical ground reaction forces, times to F1 (tF1), F2 (tF2), and the end of the impact phase, vertical impulse, and anterior-posterior and medial lateral force couples. Effect sizes (ES; large >0.8) were computed to determine the magnitude of the differences. Lower jump height (41.60 +/- 4.03 cm, VJ landings; 39.40 +/- 4.05 cm, VJR landings; p = 0.002; ES = 0.39), greater F2 (55.71 +/- 11.95 N.kg, VJ; 68.16 +/- 14.82 N.kg; p < 0.001; ES = 0.94), faster tF2 (0.057 +/- 0.012 seconds, VJ; 0.047 +/- 0.011 seconds, VJR; p = 0.001; ES = 0.89), greater anterior-posterior (0.06 +/- 0.03 N.s.kg, VJ; 0.56 +/- 0.15 N.s.kg, VJR; p < 0.001; ES = 1.83) and medial-lateral force couples (0.29 +/- 0.11 N.s.kg, VJ; 0.56 +/- 0.14 N.s.kg, VJR; p < 0.001; ES = 1.46) occurred during VJR landings. No other differences were identified. This kinetic analysis determined that landing from a jump with 180 degrees airborne rotation is different than landing from a jump without an airborne rotation. Male Division I soccer players could benefit from increasing the volume of VJR landings during training to address the differences in jump height and force parameters compared with VJ landings. PMID- 27669197 TI - Bioactivity of a Novel Glycolipid Produced by a Halophilic Buttiauxella sp. and Improving Submerged Fermentation Using a Response Surface Method. AB - An antimicrobial glycolipid biosurfactant (GBS), extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM) with a central composite design (CCD) for obtaining maximum yields on a cost effective substrate, molasses. The GBS-producing bacterium was identified as Buttiauxella Species in terms of biochemical and molecular characteristics. This compound showed a desirable antimicrobial activity against some pathogens such as E. coli, Bacillus subtilis, Bacillus cereus, Candida albicans, Aspergilus niger, Salmonella enterica. The rheological studies described the stability of the GBS at high values in a range of pH (7-8), temperature (20-60) and salinity (0%-3%). The statistical optimization of GBS fermentation was found to be pH 7, temperature 33 degrees C, Peptone 1%, NaCl 1% and molasses 1%. The potency of the GBS as an effective antimicrobial agent provides evidence for its use against food and human pathogens. Moreover, favorable production of the GBS in the presence of molasses as a cheap substrate and the feasibility of pilot scale fermentation using an RSM method could expand its uses in food, pharmaceutical products and oil industries. PMID- 27669199 TI - Identification of Metabolites of 6'-Hydroxy-3,4,5,2',4'-pentamethoxychalcone in Rats by a Combination of Ultra-High-Performance Liquid Chromatography with Linear Ion Trap-Orbitrap Mass Spectrometry Based on Multiple Data Processing Techniques. AB - In this study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of 6'-hydroxy 3,4,5,2',4'-pentamethoxychalcone (PTC) in rat urine and feces. The UHPLC-LTQ Orbitrap method combines the high trapping capacity and MS(n) scanning function of the linear ion trap along with accurate mass measurements within 5 ppm and a resolving power of up to 30,000 over a wider dynamic range compared to many other mass spectrometers. In order to reduce the potential interferences of endogenous substances, the post-acquisition processing method including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDF) were developed for metabolite detection. As a result, a total of 60 and 35 metabolites were detected in the urine and feces, respectively. The corresponding in vivo reactions such as methylation, hydroxylation, hydrogenation, decarbonylation, demethylation, dehydration, methylation, demethoxylation, sulfate conjugation, glucuronide conjugation, and their composite reactions were all detected in this study. The result on PTC metabolites significantly expanded the understanding of its pharmacological effects, and could be targets for future studies on the important chemical constituents from herbal medicines. PMID- 27669198 TI - Palladium-Catalyzed C-H Arylation of 1,2,3-Triazoles. AB - Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C-H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. PMID- 27669200 TI - Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes. AB - Plants with high amounts of antioxidants may be a promising therapy for preventing and curing UV-induced oxidative skin damage. The objective of this study was to verify the efficacy of topical formulations containing dissolved and suspended Silybum marianum extract against UVB-induced oxidative stress in guinea pig and HaCaT keratinocytes. Herbal extract was dissolved in Transcutol HP (TC) and sucrose-esters were incorporated as penetration enhancers in creams. Biocompatibility of compositions was tested on HeLa cells and HaCaT keratinocytes as in vitro models. Transepidermal water loss (TEWL) tests were performed to prove the safety of formulations in vivo. Drug release of different compositions was assessed by Franz diffusion methods. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (MDA) activities were evaluated before and after UVB irradiation in a guinea pig model and HaCaT cells. Heme oxygenase-1 (HO-1) enzyme activity was measured in the epidermis of guinea pigs treated by different creams before and after UVB irradiation. Treatment with compositions containing silymarin powder (SM) dissolved in TC and sucrose stearate SP 50 or SP 70 resulted in increased activities of all reactive oxygen species (ROS) eliminating enzymes in the case of pre- and post-treatment as well. Reduction in the levels of lipid peroxidation end products was also detected after treatment with these two compositions. Post-treatment was more effective as the increase of the activity of antioxidants was higher. Lower HO-1 enzyme levels were measured in the case of pre- and post-treatment groups compared to control groups. Therefore, this study demonstrates the effectiveness of topical formulations containing silymarin in inhibiting UVB irradiation induced oxidative stress of the skin. PMID- 27669202 TI - Potential of Natural Products in the Inhibition of Adipogenesis through Regulation of PPARgamma Expression and/or Its Transcriptional Activity. AB - Obesity is a global health problem characterized as an increase in the mass of adipose tissue. Adipogenesis is one of the key pathways that increases the mass of adipose tissue, by which preadipocytes mature into adipocytes through cell differentiation. Peroxisome proliferator-activated receptor gamma (PPARgamma), the chief regulator of adipogenesis, has been acutely investigated as a molecular target for natural products in the development of anti-obesity treatments. In this review, the regulation of PPARgamma expression by natural products through inhibition of CCAAT/enhancer-binding protein beta (C/EBPbeta) and the farnesoid X receptor (FXR), increased expression of GATA-2 and GATA-3 and activation of the Wnt/beta-catenin pathway were analyzed. Furthermore, the regulation of PPARgamma transcriptional activity associated with natural products through the antagonism of PPARgamma and activation of Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) were discussed. Lastly, regulation of mitogen-activated protein kinase (MAPK) by natural products, which might regulate both PPARgamma expression and PPARgamma transcriptional activity, was summarized. Understanding the role natural products play, as well as the mechanisms behind their regulation of PPARgamma activity is critical for future research into their therapeutic potential for fighting obesity. PMID- 27669201 TI - Enhanced Cellular Uptake and Pharmacokinetic Characteristics of Doxorubicin Valine Amide Prodrug. AB - In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (1H-NMR) assay. In the MCF-7 cells (human breast adenocarcinoma cell; amino acid transporter-positive cell), the cellular accumulation efficiency of DOX-Val was higher than that of DOX according to the flow cytometry analysis data. Using confocal laser scanning microscopy (CLSM) imaging, it was confirmed that DOX-Val as well as DOX was mainly distributed in the nucleus of cancer cells. DOX-Val was intravenously administered to rats at a dose of 4 mg/kg, and the plasma concentrations of DOX-Val (prodrug) and DOX (formed metabolite) were quantitatively determined. Based on the systemic exposure (represented as area under the curve (AUC) values) of DOX-Val (prodrug) and DOX (formed metabolite), approximately half of DOX-Val seemed to be metabolized into DOX. However, it is expected that the remaining DOX-Val may exert improved cellular uptake efficiency in cancer cells after its delivery to the cancer region. PMID- 27669204 TI - Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8 Dichloroanthracene and Acrolein. AB - A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6 31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs) favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product. PMID- 27669203 TI - Identification of Nematicidal Constituents of Notopterygium incisum Rhizomes against Bursaphelenchus xylophilus and Meloidogyne incognita. AB - During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four constituents were isolated from the ethanol extract and identified as columbianetin, falcarindiol, falcarinol, and isoimperatorin. Among the four isolated constituents, two acetylenic compounds, falcarindiol and falcarinol (2.20-12.60 MUg/mL and 1.06-4.96 MUg/mL, respectively) exhibited stronger nematicidal activity than two furanocoumarins, columbianetin, and isoimperatorin (21.83-103.44 MUg/mL and 17.21-30.91 MUg/mL, respectively) against the two species of nematodes, B. xylophilus and M. incognita. The four isolated constituents also displayed phototoxic activity against the nematodes. The results indicate that the ethanol extract of N. incisum and its four isolated constituents have potential for development into natural nematicides for control of plant-parasitic nematodes. PMID- 27669205 TI - Analysis of Flavonoids in Rhamnus davurica and Its Antiproliferative Activities. AB - Rhamnus davurica Pall. (R. davurica) has been used as a traditional medicinal herb for many years in China and abroad. It has been well documented as a rich source of flavonoids with diversified structures, which in turn results in far ranging biological activities, such as anti-inflammation, anticancer, antibacterial and antioxidant activities. In order to further correlate their anticancer potentials with the phytochemical components, the fingerprint profile of R. davurica herb from Dongbei was firstly investigated using HPLC-ESI-MS/MS. Thirty two peaks were detected and identified, 14 of which were found in R. davurica for the first time in this work. Furthermore, a total of 23 peaks were resolved as flavonoids, which are the major components found in R. davurica. Meanwhile, the antiproliferative activities against human cancer cells of HT-29 and SGC-7901 in vitro exhibited distinct inhibitory effects with IC50 values at 24.96 +/- 0.74 and 89.53 +/- 4.11 MUg/mL, respectively. Finally, the general toxicity against L-O2 cells displayed a much higher IC50 at 229.19 +/- 8.52 MUg/mL, which suggested very low or no toxicity on hepatic cell viability. The current study revealed for the first time the correlations between the flavonoids of R. davurica with their antiproliferative activities, which indicated that the fingerprint profile of flavonoids and their anticancer activities could provide valuable information on the quality control for herbal medicines and their derived natural remedies from this valuable medicinal plant. PMID- 27669206 TI - Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand? AB - Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of the anti inflammatory properties of bergamot extracts that could represent the scientific basis for develop novel and alternative strategies to improve health status and attenuate inflammatory conditions. PMID- 27669207 TI - Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide. AB - As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients' quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery. PMID- 27669208 TI - Nanostructured Samarium Doped Fluorapatites and Their Catalytic Activity towards Synthesis of 1,2,4-Triazoles. AB - An investigation was conducted into the influence of the amino acids as organic modifiers in the facile synthesis of metal incorporated fluorapatites (FAp) and their properties. The nanostructured Sm doped fluorapatites (Sm-FAp) were prepared by a co-precipitation method using four different amino acids, namely glutamic acid, aspartic acid, glycine and histidine. The materials were characterized by various techniques including X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), high resolution transmission electron microscopy (HR-TEM), N2-adsorption/desorption isotherm, temperature programmed desorption (TPD) and fluorescence spectrophotometry. Under similar conditions, Sm-FAp prepared using different amino acids exhibited distinctly different morphological structures, surface area and pore properties. Their activity as catalysts was assessed and Sm-FAp/Glycine displayed excellent efficiency in the synthesis of 1,2,4-triazole catalyzing the reaction between 2 nitrobenzaldehyde and thiosemicarbazide with exceptional selectivity and 98% yield in a short time interval (10 min). The study provides an insight into the role of organic modifiers as controllers of nucleation, growth and aggregation which significantly influence the nature and activity of the catalytic sites on Sm-FAp. Sm-FAp could also have potential as photoactive material. PMID- 27669209 TI - Cytoproliferative and Cytoprotective Effects of Striatisporolide A Isolated from Rhizomes of Athyrium multidentatum (Doell.) Ching on Human Umbilical Vein Endothelial Cells. AB - OBJECTIVES: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7 dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. RESULTS: The viability rate in cells treated with 100 uM SA alone was increased to 128.72% +/- 0.19% and showed a significant difference compared with the control group (p < 0.05). Meanwhile, SA augmented the cell viabilities in H2O2-treated HUVECs, and the cell viability was enhanced to 56.94% +/- 0.13% (p < 0.01) when pre-incubated with 50 uM SA. The cell apoptosis rates were reduced to 2.17% +/- 0.20% (p < 0.05) and 3.1% +/- 0.34% (p < 0.01), respectively, after treatment with SA alone or SA/H2O2. SA inhibited the overproduction of reactive oxygen species (ROS) in HUVECs induced by H2O2 and the fluorescent intensity was abated to 9.47 +/- 0.61 after pre-incubated with 100 MUM SA. CONCLUSIONS: The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides. PMID- 27669211 TI - Identification of Resistance to Wet Bubble Disease and Genetic Diversity in Wild and Cultivated Strains of Agaricus bisporus. AB - Outbreaks of wet bubble disease (WBD) caused by Mycogone perniciosa are increasing across the world and seriously affecting the yield of Agaricus bisporus. However, highly WBD-resistant strains are rare. Here, we tested 28 A. bisporus strains for WBD resistance by inoculating M. perniciosa spore suspension on casing soil, and assessed genetic diversity of these strains using 17 new simple sequence repeat (SSR) markers developed in this study. We found that 10 wild strains originating from the Tibetan Plateau in China were highly WBD resistant strains, and 13 cultivated strains from six countries were highly susceptible strains. A total of 88 alleles were detected in these 28 strains, and the observed number of alleles per locus ranged from 2 to 8. Cluster and genetic structure analysis results revealed the wild resources from China have a relatively high level of genetic diversity and occur at low level of gene flow and introgression with cultivated strains. Moreover, the wild strains from China potentially have the consensus ancestral genotypes different from the cultivated strains and evolved independently. Therefore, the highly WBD-resistant wild strains from China and newly developed SSR markers could be used as novel sources for WBD-resistant breeding and quantitative trait locus (QTL) mapping of WBD resistant gene of A. bisporus. PMID- 27669210 TI - Histone Posttranslational Modifications of CD4+ T Cell in Autoimmune Diseases. AB - The complexity of immune system is tempered by precise regulation to maintain stabilization when exposed to various conditions. A subtle change in gene expression may be magnified when drastic changes are brought about in cellular development and function. Posttranslational modifications (PTMs) timely alter the functional activity of immune system, and work proceeded in these years has begun to throw light upon it. Posttranslational modifications of histone tails have been mentioned in a large scale of biological developments and disease progression, thereby making them a central field to investigate. Conventional assessments of these changes are centered on the transcription factors and cytokines in T cells regulated by variable histone codes to achieve chromatin remodeling, as well as involved in many human diseases, especially autoimmune diseases. We here put forward an essential review of core posttranslational modulations that regulate T cell function and differentiation in the immune system, with a special emphasis on histone modifications in different T helper cell subsets as well as in autoimmune diseases. PMID- 27669213 TI - Characterization of a beta-Adrenergic-Like Octopamine Receptor in the Oriental Fruit Fly, Bactrocera dorsalis (Hendel). AB - The biogenic amine octopamine plays a critical role in the regulation of many physiological processes in insects. Octopamine transmits its action through a set of specific G-protein coupled receptors (GPCRs), namely octopamine receptors. Here, we report on a beta-adrenergic-like octopamine receptor gene (BdOctbetaR1) from the oriental fruit fly, Bactrocera dorsalis (Hendel), a destructive agricultural pest that occurs in North America and the Asia-Pacific region. As indicated by RT-qPCR, BdOctbetaR1 was highly expressed in the central nervous system (CNS) and Malpighian tubules (MT) in the adult flies, suggesting it may undertake important roles in neural signaling in the CNS as well as physiological functions in the MT of this fly. Furthermore, its ligand specificities were tested in a heterologous expression system where BdOctbetaR1 was expressed in HEK 293 cells. Based on cyclic AMP response assays, we found that BdOctbetaR1 could be activated by octopamine in a concentration-dependent manner, confirming that this receptor was functional, while tyramine and dopamine had much less potency than octopamine. Naphazoline possessed the highest agonistic activity among the tested agonists. In antagonistic assays, mianserin had the strongest activity and was followed by phentolamine and chlorpromazine. Furthermore, when the flies were kept under starvation, there was a corresponding increase in the transcript level of BdOctbetaR1, while high or low temperature stress could not induce significant expression changes. The above results suggest that BdOctbetaR1 may be involved in the regulation of feeding processes in Bactrocera dorsalis and may provide new potential insecticide leads targeting octopamine receptors. PMID- 27669212 TI - Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats. AB - Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14-21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-gamma) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN gamma promoter correlated with decreased IFN-gamma production. The impaired IFN gamma production and aberrant site-specific histone modification at the IFN-gamma promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-gamma production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID- 27669214 TI - Fine Mapping of Virescent Leaf Gene v-1 in Cucumber (Cucumis sativus L.). AB - Leaf color mutants are common in higher plants that can be used as markers in crop breeding or as an important tool in understanding regulatory mechanisms in chlorophyll biosynthesis and chloroplast development. In virescent leaf mutants, young leaves are yellow in color, which gradually return to normal green when the seedlings grow large. In the present study, we conducted phenotypic characterization and genetic mapping of the cucumber virescent leaf mutant 9110Gt conferred by the v-1 locus. Total chlorophyll and carotenoid content in 9110Gt was reduced by 44% and 21%, respectively, as compared with its wild type parental line 9110G. Electron microscopic investigation revealed fewer chloroplasts per cell and thylakoids per chloroplast in 9110Gt than in 9110G. Fine genetic mapping allowed for the assignment of the v-1 locus to a 50.4 kb genomic DNA region in chromosome 6 with two flanking markers that were 0.14 and 0.16 cM away from v-1, respectively. Multiple lines of evidence supported CsaCNGCs as the only candidate gene for the v-1 locus, which encoded a cyclic-nucleotide-gated ion channel protein. A single nucleotide change in the promoter region of v-1 seemed to be associated with the virescent color change in 9110Gt. Real-time PCR revealed significantly lower expression of CsaCNGCs in the true leaves of 9110Gt than in 9110G. This was the first report that connected the CsaCNGCs gene to virescent leaf color change, which provided a useful tool to establish linkages among virescent leaf color change, chloroplast development, chlorophyll biosynthesis, and the functions of the CsaCNGCs gene. PMID- 27669216 TI - Protein/CaCO3/Chitin Nanofiber Complex Prepared from Crab Shells by Simple Mechanical Treatment and Its Effect on Plant Growth. AB - A protein/CaCO3/chitin nanofiber complex was prepared from crab shells by a simple mechanical treatment with a high-pressure water-jet (HPWJ) system. The preparation process did not involve chemical treatments, such as removal of protein and calcium carbonate with sodium hydroxide and hydrochloric acid, respectively. Thus, it was economically and environmentally friendly. The nanofibers obtained had uniform width and dispersed homogeneously in water. Nanofibers were characterized in morphology, transparency, and viscosity. Results indicated that the shell was mostly disintegrated into nanofibers at above five cycles of the HPWJ system. The chemical structure of the nanofiber was maintained even after extensive mechanical treatments. Subsequently, the nanofiber complex was found to improve the growth of tomatoes in a hydroponics system, suggesting the mechanical treatments efficiently released minerals into the system. The homogeneous dispersion of the nanofiber complex enabled easier application as a fertilizer compared to the crab shell flakes. PMID- 27669215 TI - Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk. AB - Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1alpha-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p < 0.001-0.05). No significant connection was seen between NSCLC risk and overall plasma 25-hydroxyvitamin D [25(OH)D] concentrations, regardless of smoking status. However, the mutation genotype of CYP24A1 rs6068816 and VDR rs1544410 were also significantly associated with increased 25(OH)D levels only in both the smoker and non-smoker cases (p < 0.01 0.05). Meanwhile, smokers and non-smokers with mutated homozygous rs2181874 in CYP24A1 had significantly increased NSCLC risk (odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.47-3.43; p = 0.031; OR = 3.57, 95% CI 2.66-4.74; p = 0.019, respectively). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41-2.76; p = 0.015). However, smokers with mutated homozygous rs6068816 in CYP24A1 had significantly decreased NSCLC risk (OR = 0.43, 95% CI 0.27-1.02; p = 0.006); and smokers and non-smokers with mutated homozygous rs1544410 in VDR had significantly decreased NSCLC risk (OR = 0.51, 95% CI 0.34-1.17; p = 0.002; OR = 0.26, 95% CI 0.20-0.69; p = 0.001, respectively). There are significant joint effects between smoking and CYP24A1 rs2181874, CYP24A1 rs6068816, VDR rs10735810, and VDR rs1544410 (p < 0.01 0.05). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41-2.76; p = 0.015). In summary, the results suggested that the lower the distribution of vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk. PMID- 27669217 TI - Inducible Expression of both ermB and ermT Conferred High Macrolide Resistance in Streptococcus gallolyticus subsp. pasteurianus Isolates in China. AB - Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010-2013. All isolates exhibited multi-drug resistance including high macrolide resistance (MIC >= 1024 mg/L for erythromycin, and 512 mg/L for clarithromycin). Efflux-encoding mefA and mefE genes were not detectable in these isolates. The presence of 23S rRNA mutations in specific isolates did not significantly change macrolide MICs. No nucleotide substitutions were found in genes encoding ribosomal proteins L4 or L22. The ermB and ermT genes were found in the genomes of all isolates. These two genes were acquired independently in one highly virulent isolate AL101002, and clustered with Tn916 and IS1216, respectively. The expression of both ermB and ermT in all isolates was erythromycin inducible and yielded comparable macrolide MICs in all six isolates. Taken together, inducible expression of both ermB and ermT conferred high macrolide resistance in these S. gallolyticus subsp. pasterianus isolates. Our findings reveal new macrolide resistance features in S. gallolyticus subsp. pasteurianus by both ermB and ermT. PMID- 27669220 TI - A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells. AB - Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro apoptotic effects of a novel fatty acid isolated from A. spinosus (14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate-against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2). The MTT assay showed that the fatty acid markedly inhibited the proliferation of HepG2 cells in a dosage-dependent fashion, with a half maximal inhibitory concentration (IC50) value of 25.52 umol/L. This antiproliferative result was superior to that of another known fatty acid, linoleic acid (IC50 38.65 umol/L), but comparable to that of standard anticancer drug doxorubicin (IC50 24.68 umol/L). The novel fatty acid also induced apoptosis mediated by downregulation of cyclin B1, upregulation of Bax, and downregulation of Bcl-2, resulting in the G2/M transition arrest. Our results provide the first experimental evidence that a novel fatty acid isolated from A. spinosus exhibits significant antiproliferative activity mediated through the induction of apoptosis in HepG2 cells. These encouraging results may facilitate the development of A. spinosus fatty acid for the prevention and intervention of hepatocellular carcinoma. PMID- 27669219 TI - MicroRNA Transcriptome of Poly I:C-Stimulated Peripheral Blood Mononuclear Cells Reveals Evidence for MicroRNAs in Regulating Host Response to RNA Viruses in Pigs. AB - MicroRNAs (miRNAs) are one family of small noncoding RNAs that function to modulate the activity of specific mRNA targets in animals. To understand the role of miRNAs in regulating genes involved in the host immune response to RNA viruses, we profiled and characterized the miRNAs of swine peripheral blood mononuclear cells (PBMC) stimulated with poly I:C, a synthetic dsRNA analog, by miRNA-sequencing (miRNA-seq). We identified a total of 905 miRNAs, of which 503 miRNAs were firstly exploited herein with no annotation in the latest miRBase 21.0. Expression analysis demonstrated that poly I:C stimulation can elicit significantly differentially expressed (DE) miRNAs in Dapulian (n = 20), one Chinese indigenous breed, as well as Landrace (n = 23). By integrating the mRNA expression profiles of the same sample with miRNA profiles, we carried out function analyses of the target genes of these DE miRNAs, with the results indicating that target genes were most enriched in some immune-related pathways and gene ontology (GO) terms, suggesting that DE miRNAs play an important role in the regulation of host to poly I:C stimulation. Furthermore, we also detected 43 and 61 significantly DE miRNAs between the two breeds in the control sample groups and poly I:C stimulation groups, respectively, which may be involved in regulation of the different characteristics of the two breeds. This study describes for the first time the PBMC miRNA transcriptomic response to poly I:C stimulation in pigs, which not only contributes to a broad view of the pig miRNAome but improves our understanding of miRNA function in regulating host immune response to RNA viruses. PMID- 27669218 TI - Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review. AB - Tocotrienol (T3), unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc). Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti metastasis, nuclear factor-kappaB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the alpha-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of alpha Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib) or dietary components (e.g., polyphenols, sesamin, and ferulic acid) exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy. PMID- 27669222 TI - Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions. AB - Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson's trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor beta1 (TGF-beta1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF beta1, fibrinogen and alpha-smooth muscle actin (alpha-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor alpha (TNF-alpha) and TGF-beta1 in the abdominal fluid. The expression levels of TGF-beta1, fibrinogen and alpha-SMA protein and mRNA in the rat peritoneum or adhesion tissues were also down-regulated following the combined administration of KGF and HA. The combined administration of KGF and HA can significantly prevent postoperative intra-abdominal adhesion formation by maintaining the separation of the injured peritoneum and promoting mesothelial cell regeneration. The potential mechanism may be associated with rapid mesothelial cell repair in the injured peritoneum. This study suggests that combined administration of KGF and HA may be a promising pharmacotherapeutic strategy for preventing abdominal adhesions, which is worth further study, and has potential value in clinical applications. PMID- 27669221 TI - Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model. AB - Silver nanoparticles (AgNPs) have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with future perspectives on research into AgNPs. PMID- 27669223 TI - Designing Efficient Double RNA trans-Splicing Molecules for Targeted RNA Repair. AB - RNA trans-splicing is a promising tool for mRNA modification in a diversity of genetic disorders. In particular, the substitution of internal exons of a gene by combining 3' and 5' RNA trans-splicing seems to be an elegant way to modify especially large pre-mRNAs. Here we discuss a robust method for designing double RNA trans-splicing molecules (dRTM). We demonstrate how the technique can be implemented in an endogenous setting, using COL7A1, the gene encoding type VII collagen, as a target. An RTM screening system was developed with the aim of testing the replacement of two internal COL7A1 exons, harbouring a homozygous mutation, with the wild-type version. The most efficient RTMs from a pool of randomly generated variants were selected via our fluorescence-based screening system and adapted for use in an in vitro disease model system. Transduction of type VII collagen-deficient keratinocytes with the selected dRTM led to accurate replacement of two internal COL7A1 exons resulting in a restored wild-type RNA sequence. This is the first study demonstrating specific exon replacement by double RNA trans-splicing within an endogenous transcript in cultured cells, corroborating the utility of this technology for mRNA repair in a variety of genetic disorders. PMID- 27669224 TI - Virus-Induced Gene Silencing Identifies an Important Role of the TaRSR1 Transcription Factor in Starch Synthesis in Bread Wheat. AB - The function of a wheat starch regulator 1 (TaRSR1) in regulating the synthesis of grain storage starch was determined using the barley stripe mosaic virus-virus induced gene-silencing (BSMV-VIGS) method in field experiments. Chlorotic stripes appeared on the wheat spikes infected with barley stripe mosaic virus-virus induced gene-silencing- wheat starch regulator 1 (BSMV-VIGS-TaRSR1) at 15 days after anthesis, at which time the transcription levels of the TaRSR1 gene significantly decreased. Quantitative real-time PCR was also used to measure the transcription levels of 26 starch synthesis-related enzyme genes in the grains of BSMV-VIGS-TaRSR1-silenced wheat plants at 20, 27, and 31 days after anthesis. The results showed that the transcription levels of some starch synthesis-related enzyme genes were markedly induced at different sampling time points: TaSSI, TaSSIV, TaBEIII, TaISA1, TaISA3, TaPHOL, and TaDPE1 genes were induced at each of the three sampling time points and TaAGPS1-b, TaAGPL1, TaAGPL2, TaSSIIb, TaSSIIc, TaSSIIIb, TaBEI, TaBEIIa, TaBEIIb, TaISA2, TaPHOH, and TaDPE2 genes were induced at one sampling time point. Moreover, both the grain starch contents, one thousand kernel weights, grain length and width of BSMV-VIGS-TaRSR1-infected wheat plants significantly increased. These results suggest that TaRSR1 acts as a negative regulator and plays an important role in starch synthesis in wheat grains by temporally regulating the expression of specific starch synthesis related enzyme genes. PMID- 27669225 TI - PlGF and VEGF-A Regulate Growth of High-Risk MYCN-Single Copy Neuroblastoma Xenografts via Different Mechanisms. AB - Neuroblastoma (NB) is the most common extracranial solid tumor of childhood and is a rapidly growing, highly-vascularized cancer. NBs frequently express angiogenic factors and high tumor angiogenesis has been associated with poor outcomes. Placental growth factor (PlGF) is an angiogenic protein belonging to the vascular endothelial growth factor (VEGF) family and is up-regulated mainly in pathologic conditions. Recently, PlGF was identified as a member of a gene expression signature characterizing highly malignant NB stem cells drawing attention as a potential therapeutic target in NB. In the present study, we sought to investigate the expression of PlGF in NB patients and the effect of PlGF inhibition on high-risk MYCN-non-amplified SK-N-AS NB xenografts. Human SK-N AS cells, which are poorly differentiated and express PlGF and VEGF-A, were implanted subcutaneously in athymic nude mice. Treatment was done by intratumoral injection of replication-incompetent adenoviruses (Ad) expressing PlGF- or VEGF specific short hairpin (sh)RNA, or soluble (s)VEGF receptor 2 (VEGFR2). The effect on tumor growth and angiogenesis was analyzed. High PlGF expression levels were observed in human advanced-stage NBs. Down-regulating PlGF significantly reduced NB growth in established NB xenografts by reducing cancer cell proliferation but did not suppress angiogenesis. In contrast, blocking VEGF by administration of Ad(sh)VEGF and Ad(s)VEGFR2 reduced tumor growth associated with decreased tumor vasculature. These findings suggest that PlGF and VEGF-A modulate MYCN-non-amplified NB tumors by different mechanisms and support a role for PlGF in NB biology. PMID- 27669226 TI - APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome. AB - The proteasome is a multienzymatic complex that controls the half-life of the majority of intracellular proteins, including those involved in apoptosis and cell-cycle progression. Recently, proteasome inhibition has been shown to be an effective anticancer strategy, although its downregulation is often accompanied by severe undesired side effects. We previously reported that the inhibition of acylpeptide hydrolase (APEH) by the peptide SsCEI 4 can significantly affect the proteasome activity in A375 melanoma or Caco-2 adenocarcinoma cell lines, thus shedding new light on therapeutic strategies based on downstream regulation of proteasome functions. In this work, we investigated the functional correlation between APEH and proteasome in a panel of cancer cell lines, and evaluated the cell proliferation upon SsCEI 4-treatments. Results revealed that SsCEI 4 triggered a proliferative arrest specifically in osteosarcoma U2OS cells via downregulation of the APEH-proteasome system, with the accumulation of the typical hallmarks of proteasome: NF-kappaB, p21(Waf1), and polyubiquitinylated proteins. We found that the SsCEI 4 anti-proliferative effect involved a senescence-like growth arrest without noticeable cytotoxicity. These findings represent an important step toward understanding the mechanism(s) underlying the APEH-mediated downregulation of proteasome in order to design new molecules able to efficiently regulate the proteasome system for alternative therapeutic strategies. PMID- 27669228 TI - Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry. AB - Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain metastases (BMs) were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC) in Germany. Patients with positive estrogen (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2) statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001). Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021), whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038). The localization of Brain metastases (BMs) was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025). A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012). Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment. PMID- 27669227 TI - Waste Soybean Oil and Corn Steep Liquor as Economic Substrates for Bioemulsifier and Biodiesel Production by Candida lipolytica UCP 0998. AB - Almost all oleaginous microorganisms are available for biodiesel production, and for the mechanism of oil accumulation, which is what makes a microbial approach economically competitive. This study investigated the potential that the yeast Candida lipolytica UCP0988, in an anamorphous state, has to produce simultaneously a bioemulsifier and to accumulate lipids using inexpensive and alternative substrates. Cultivation was carried out using waste soybean oil and corn steep liquor in accordance with 22 experimental designs with 1% inoculums (107 cells/mL). The bioemulsifier was produced in the cell-free metabolic liquid in the late exponential phase (96 h), at Assay 4 (corn steep liquor 5% and waste soybean oil 8%), with 6.704 UEA, IE24 of 96.66%, and showed an anionic profile. The emulsion formed consisted of compact small and stable droplets (size 0.2-5 um), stable at all temperatures, at pH 2 and 4, and 2% salinity, and showed an ability to remove 93.74% of diesel oil from sand. The displacement oil (ODA) showed 45.34 cm2 of dispersion (central point of the factorial design). The biomass obtained from Assay 4 was able to accumulate lipids of 0.425 g/g biomass (corresponding to 42.5%), which consisted of Palmitic acid (28.4%), Stearic acid (7.7%), Oleic acid (42.8%), Linoleic acid (19.0%), and gamma-Linolenic acid (2.1%). The results showed the ability of C. lipopytica to produce both bioemulsifier and biodiesel using the metabolic conversion of waste soybean oil and corn steep liquor, which are economic renewable sources. PMID- 27669231 TI - Development of 12 Microsatellite Markers in Dorcus titanus castanicolor (Motschulsky, 1861) (Lucanidae, Coleoptera) from Korea Using Next-Generation Sequencing. AB - In the present study, we used next-generation sequencing to develop 12 novel microsatellite markers for genetic structural analysis of Dorcus titanus castanicolor (Lucanidae; Coleoptera), a popular pet insect in China, Korea, and Japan. We identified 52,357 microsatellite loci in 339,287,381 bp of genomic sequence and selected 19 of the loci based on their PCR amplification efficiency and polymorphism. The 19 selected markers were then tested for the presence of null alleles and linkage disequilibrium. We did not detect any evidence of null alleles; however, four pairs of loci (DT03 and DT11, DT05 and DT26, DT08 and DT26, DT26 and DT35) exhibited linkage disequilibrium. Thus, we assessed the genetic diversity of a D. titanus castanicolor population from the Daejeon region of Korea (n = 22) using 13 markers. Among them, one marker (DT17) deviated from Hardy-Weinberg equilibrium. Therefore, 12 markers may be useful for further analyzing the genetic diversity of D. titanus castanicolor. PMID- 27669230 TI - Genome-Wide Characterization and Expression Analysis of the Germin-Like Protein Family in Rice and Arabidopsis. AB - Previous studies have shown that germin-like proteins (GLPs) are present ubiquitously in rice and Arabidopsis. However, the understanding regarding their role in development and abiotic/biotic stress resistance remains limited. In the present study, we report genome-wide identification, characterisation, subcellular localization, enzyme activity, and expression analysis of the GLP gene family in rice and Arabidopsis to study their functions. In total, 43 and 32 GLPs in the rice and Arabidopsis genome were identified based on a systematic analysis, respectively. The GLP genes were clustered into six clades based on phylogenetic analysis, and many stress and developmental-related cis-elements were detected in promoters of GLP genes. In addition, subcellular location and superoxide dismutase (SOD) analysis demonstrated that the random selected OsGLP genes on chromosomes 8 and 4 of rice were expressed in the cell wall with SOD activity. Overall, our results showed that tandem duplication events, especially the clusters of tandem duplication genes on chromosome 8 in rice, play a major role in expansion of the GLP family and thus increase our understanding of the role of the GLP family in abiotic/biotic stress and development. PMID- 27669229 TI - The Epidermal Growth Factor Receptor (EGFR) Inhibitor Gefitinib Reduces but Does Not Prevent Tumorigenesis in Chemical and Hormonal Induced Hepatocarcinogenesis Rat Models. AB - Activation of the epidermal growth factor receptor (EGFR) signaling pathway promotes the development of hepatocellular adenoma (HCA) and carcinoma (HCC). The selective EGFR inhibitor Gefitinib was found to prevent hepatocarcinogenesis in rat cirrhotic livers. Thus, Gefitinib might reduce progression of pre-neoplastic liver lesions to HCC. In short- and long-term experiments, administration of N Nitrosomorpholine (NNM) or intrahepatic transplantation of pancreatic islets in diabetic (PTx), thyroid follicles in thyroidectomized (TTx) and ovarian fragments in ovariectomized (OTx) rats was conducted for the induction of foci of altered hepatocytes (FAH). Gefitinib was administered for two weeks (20 mg/kg) or three and nine months (10 mg/kg). In NNM-treated rats, Gefitinib administration decreased the amount of FAH when compared to controls. The amount of HCA and HCC was decreased, but development was not prevented. Upon all transplantation models, proliferative activity of FAH was lower after administration of Gefitinib in short-term experiments. Nevertheless, the burden of HCA and HCC was not changed in later stages. Thus, EGFR inhibition by Gefitinib diminishes chemical and hormonal also induced hepatocarcinogenesis in the initiation stage in the non cirrhotic liver. However, progression to malignant hepatocellular tumors was not prevented, indicating only a limited relevance of the EGFR signaling cascade in later stages of hepatocarcinogenesis. PMID- 27669232 TI - Long Noncoding RNA lncCAMTA1 Promotes Proliferation and Cancer Stem Cell-Like Properties of Liver Cancer by Inhibiting CAMTA1. AB - Hepatocellular carcinoma (HCC) is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC) mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA) microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome. In vitro and in vivo functional experiments showed that overexpression of lncCAMTA1 promotes HCC cell proliferation, CSC-like properties, and tumorigenesis. Conversely, depletion of lncCAMTA1 inhibits HCC cell proliferation, CSC-like properties, and tumorigenesis. Mechanistically, we demonstrated that lncCAMTA1 physically associates with the calmodulin binding transcription activator 1 (CAMTA1) promoter, induces a repressive chromatin structure, and inhibits CAMTA1 transcription. Furthermore, CAMTA1 is required for the effects of lncCAMTA1 on HCC cell proliferation and CSC-like properties, and the expression of lncCAMTA1 and CAMTA1 is significantly negatively correlated in HCC tissues. Collectively, our study revealed the important roles and underlying molecular mechanisms of lncCAMTA1 on HCC, and suggested that lncCAMTA1 could be an effective prognostic factor and a potential therapeutic target for HCC. PMID- 27669233 TI - Hepatic Fasting-Induced PPARalpha Activity Does Not Depend on Essential Fatty Acids. AB - The liver plays a central role in the regulation of fatty acid metabolism, which is highly sensitive to transcriptional responses to nutrients and hormones. Transcription factors involved in this process include nuclear hormone receptors. One such receptor, PPARalpha, which is highly expressed in the liver and activated by a variety of fatty acids, is a critical regulator of hepatic fatty acid catabolism during fasting. The present study compared the influence of dietary fatty acids and fasting on hepatic PPARalpha-dependent responses. Pparalpha(-/-) male mice and their wild-type controls were fed diets containing different fatty acids for 10 weeks prior to being subjected to fasting or normal feeding. In line with the role of PPARalpha in sensing dietary fatty acids, changes in chronic dietary fat consumption influenced liver damage during fasting. The changes were particularly marked in mice fed diets lacking essential fatty acids. However, fasting, rather than specific dietary fatty acids, induced acute PPARalpha activity in the liver. Taken together, the data imply that the potent signalling involved in triggering PPARalpha activity during fasting does not rely on essential fatty acid-derived ligand. PMID- 27669235 TI - New Potential Biomarker for Methasterone Misuse in Human Urine by Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry. AB - In this study, methasterone urinary metabolic profiles were investigated by liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) in full scan and targeted MS/MS modes with accurate mass measurement. A healthy male volunteer was asked to take the drug and liquid-liquid extraction was employed to process urine samples. Chromatographic peaks for potential metabolites were hunted out with the theoretical [M - H](-) as a target ion in a full scan experiment and actual deprotonated ions were studied in targeted MS/MS experiment. Fifteen metabolites including two new sulfates (S1 and S2), three glucuronide conjugates (G2, G6 and G7), and three free metabolites (M2, M4 and M6) were detected for methasterone. Three metabolites involving G4, G5 and M5 were obtained for the first time in human urine samples. Owing to the absence of helpful fragments to elucidate the steroid ring structure of methasterone phase II metabolites, gas chromatography mass spectrometry (GC-MS) was employed to obtain structural information of the trimethylsilylated phase I metabolite released after enzymatic hydrolysis and the potential structure was inferred using a combined MS method. Metabolite detection times were also analyzed and G2 (18-nor-17beta-hydroxymethyl-2alpha, 17alpha-dimethyl-androst-13-en-3alpha-ol-xi O-glucuronide) was thought to be new potential biomarker for methasterone misuse which can be detected up to 10 days. PMID- 27669234 TI - Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa. AB - In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1beta, IL 2, IL-6, IL-10, tumor necrosis factor-beta, and interferon-gamma (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease. PMID- 27669237 TI - Direct LAMP Assay without Prior DNA Purification for Sex Determination of Papaya. AB - Papaya (Carica papaya L.) is an economically important tropical fruit tree with hermaphrodite, male and female sex types. Hermaphroditic plants are the major type used for papaya production because their fruits have more commercial advantages than those of female plants. Sex determination of the seedlings, or during the early growth stages, is very important for the papaya seedling industry. Thus far, the only method for determining the sex type of a papaya at the seedling stage has been DNA analysis. In this study, a molecular technique based on DNA analysis-was developed for detecting male-hermaphrodite-specific markers to examine the papaya's sex type. This method is based on the loop mediated isothermal amplification (LAMP) and does not require prior DNA purification. The results show that the method is an easy, efficient, and inexpensive way to determine a papaya's sex. This is the first report on the LAMP assay, using intact plant materials-without DNA purification-as samples for the analysis of sex determination of papaya. We found that using high-efficiency DNA polymerase was essential for successful DNA amplification, using trace intact plant material as a template DNA source. PMID- 27669238 TI - Potential of LC Coupled to Fluorescence Detection in Food Metabolomics: Determination of Phenolic Compounds in Virgin Olive Oil. AB - A powerful chromatographic method coupled to a fluorescence detector was developed to determine the phenolic compounds present in virgin olive oil (VOO), with the aim to propose an appropriate alternative to liquid chromatography-mass spectrometry. An excitation wavelength of 285 nm was selected and four different emission wavelengths (316, 328, 350 and 450 nm) were simultaneously recorded, working therefore on "multi-emission" detection mode. With the use of commercially available standards and other standards obtained by semipreparative high performance liquid chromatography, it was possible to identify simple phenols, lignans, several complex phenols, and other phenolic compounds present in the matrix under study. A total of 26 phenolic compounds belonging to different chemical families were identified (23 of them were susceptible of being quantified). The proposed methodology provided detection and quantification limits within the ranges of 0.004-7.143 MUg.mL(-1) and 0.013-23.810 MUg.mL(-1), respectively. As far as the repeatability is concerned, the relative standard deviation values were below 0.43% for retention time, and 9.05% for peak area. The developed methodology was applied for the determination of phenolic compounds in ten VOOs, both monovarietals and blends. Secoiridoids were the most abundant fraction in all the samples, followed by simple phenolic alcohols, lignans, flavonoids, and phenolic acids (being the abundance order of the latter chemical classes logically depending on the variety and origin of the VOOs). PMID- 27669236 TI - miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease. AB - Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH. PMID- 27669239 TI - Identification of Protein-Protein Interactions via a Novel Matrix-Based Sequence Representation Model with Amino Acid Contact Information. AB - Identification of protein-protein interactions (PPIs) is a difficult and important problem in biology. Since experimental methods for predicting PPIs are both expensive and time-consuming, many computational methods have been developed to predict PPIs and interaction networks, which can be used to complement experimental approaches. However, these methods have limitations to overcome. They need a large number of homology proteins or literature to be applied in their method. In this paper, we propose a novel matrix-based protein sequence representation approach to predict PPIs, using an ensemble learning method for classification. We construct the matrix of Amino Acid Contact (AAC), based on the statistical analysis of residue-pairing frequencies in a database of 6323 protein protein complexes. We first represent the protein sequence as a Substitution Matrix Representation (SMR) matrix. Then, the feature vector is extracted by applying algorithms of Histogram of Oriented Gradient (HOG) and Singular Value Decomposition (SVD) on the SMR matrix. Finally, we feed the feature vector into a Random Forest (RF) for judging interaction pairs and non-interaction pairs. Our method is applied to several PPI datasets to evaluate its performance. On the S . c e r e v i s i a e dataset, our method achieves 94 . 83 % accuracy and 92 . 40 % sensitivity. Compared with existing methods, and the accuracy of our method is increased by 0 . 11 percentage points. On the H . p y l o r i dataset, our method achieves 89 . 06 % accuracy and 88 . 15 % sensitivity, the accuracy of our method is increased by 0 . 76 % . On the H u m a n PPI dataset, our method achieves 97 . 60 % accuracy and 96 . 37 % sensitivity, and the accuracy of our method is increased by 1 . 30 % . In addition, we test our method on a very important PPI network, and it achieves 92 . 71 % accuracy. In the Wnt-related network, the accuracy of our method is increased by 16 . 67 % . The source code and all datasets are available at https://figshare.com/s/580c11dce13e63cb9a53. PMID- 27669241 TI - Performance Evaluation of Analog Beamforming with Hardware Impairments for mmW Massive MIMO Communication in an Urban Scenario. AB - The use of massive multiple-input multiple-output (MIMO) techniques for communication at millimeter-Wave (mmW) frequency bands has become a key enabler to meet the data rate demands of the upcoming fifth generation (5G) cellular systems. In particular, analog and hybrid beamforming solutions are receiving increasing attention as less expensive and more power efficient alternatives to fully digital precoding schemes. Despite their proven good performance in simple setups, their suitability for realistic cellular systems with many interfering base stations and users is still unclear. Furthermore, the performance of massive MIMO beamforming and precoding methods are in practice also affected by practical limitations and hardware constraints. In this sense, this paper assesses the performance of digital precoding and analog beamforming in an urban cellular system with an accurate mmW channel model under both ideal and realistic assumptions. The results show that analog beamforming can reach the performance of fully digital maximum ratio transmission under line of sight conditions and with a sufficient number of parallel radio-frequency (RF) chains, especially when the practical limitations of outdated channel information and per antenna power constraints are considered. This work also shows the impact of the phase shifter errors and combiner losses introduced by real phase shifter and combiner implementations over analog beamforming, where the former ones have minor impact on the performance, while the latter ones determine the optimum number of RF chains to be used in practice. PMID- 27669242 TI - Reference Beam Pattern Design for Frequency Invariant Beamforming Based on Fast Fourier Transform. AB - In the field of fast Fourier transform (FFT)-based frequency invariant beamforming (FIB), there is still an unsolved problem. That is the selection of the reference beam to make the designed wideband pattern frequency invariant (FI) over a given frequency range. This problem is studied in this paper. The research shows that for a given array, the selection of the reference beam pattern is determined by the number of sensors and the ratio of the highest frequency to the lowest frequency of the signal (RHL). The length of the weight vector corresponding to a given reference beam pattern depends on the reference frequency. In addition, the upper bound of the weight length to ensure the FI property over the whole frequency band of interest is also given. When the constraints are added to the reference beam, it does not affect the FI property of the designed wideband beam as long as the symmetry of the reference beam is ensured. Based on this conclusion, a scheme for reference beam design is proposed. PMID- 27669240 TI - Extracts of Magnolia Species-Induced Prevention of Diabetic Complications: A Brief Review. AB - Diabetic complications are the major cause of mortality for the patients with diabetes. Oxidative stress and inflammation have been recognized as important contributors for the development of many diabetic complications, such as diabetic nephropathy, hepatopathy, cardiomyopathy, and other cardiovascular diseases. Several studies have established the anti-inflammatory and oxidative roles of bioactive constituents in Magnolia bark, which has been widely used in the traditional herbal medicines in Chinese society. These findings have attracted various scientists to investigate the effect of bioactive constituents in Magnolia bark on diabetic complications. The aim of this review is to present a systematic overview of bioactive constituents in Magnolia bark that induce the prevention of obesity, hyperglycemia, hyperlipidemia, and diabetic complications, including cardiovascular, liver, and kidney. PMID- 27669243 TI - Gateway-Assisted Retransmission for Lightweight and Reliable IoT Communications. AB - Message Queuing Telemetry Transport for Sensor Networks (MQTT-SN) and Constrained Application Protocol (CoAP) are two protocols supporting publish/subscribe models for IoT devices to publish messages to interested subscribers. Retransmission mechanisms are introduced to compensate for the lack of data reliability. If the device does not receive the acknowledgement (ACK) before retransmission timeout (RTO) expires, the device will retransmit data. Setting an appropriate RTO is important because the delay may be large or retransmission may be too frequent when the RTO is inappropriate. We propose a Gateway-assisted CoAP (GaCoAP) to dynamically compute RTO for devices. Simulation models are proposed to investigate the performance of GaCoAP compared with four other methods. The experiment results show that GaCoAP is more suitable for IoT devices. PMID- 27669244 TI - An Off-Grid Turbo Channel Estimation Algorithm for Millimeter Wave Communications. AB - The bandwidth shortage has motivated the exploration of the millimeter wave (mmWave) frequency spectrum for future communication networks. To compensate for the severe propagation attenuation in the mmWave band, massive antenna arrays can be adopted at both the transmitter and receiver to provide large array gains via directional beamforming. To achieve such array gains, channel estimation (CE) with high resolution and low latency is of great importance for mmWave communications. However, classic super-resolution subspace CE methods such as multiple signal classification (MUSIC) and estimation of signal parameters via rotation invariant technique (ESPRIT) cannot be applied here due to RF chain constraints. In this paper, an enhanced CE algorithm is developed for the off grid problem when quantizing the angles of mmWave channel in the spatial domain where off-grid problem refers to the scenario that angles do not lie on the quantization grids with high probability, and it results in power leakage and severe reduction of the CE performance. A new model is first proposed to formulate the off-grid problem. The new model divides the continuously distributed angle into a quantized discrete grid part, referred to as the integral grid angle, and an offset part, termed fractional off-grid angle. Accordingly, an iterative off-grid turbo CE (IOTCE) algorithm is proposed to renew and upgrade the CE between the integral grid part and the fractional off grid part under the Turbo principle. By fully exploiting the sparse structure of mmWave channels, the integral grid part is estimated by a soft-decoding based compressed sensing (CS) method called improved turbo compressed channel sensing (ITCCS). It iteratively updates the soft information between the linear minimum mean square error (LMMSE) estimator and the sparsity combiner. Monte Carlo simulations are presented to evaluate the performance of the proposed method, and the results show that it enhances the angle detection resolution greatly. PMID- 27669245 TI - Analysis of Uncertainty in a Middle-Cost Device for 3D Measurements in BIM Perspective. AB - Medium-cost devices equipped with sensors are being developed to get 3D measurements. Some allow for generating geometric models and point clouds. Nevertheless, the accuracy of these measurements should be evaluated, taking into account the requirements of the Building Information Model (BIM). This paper analyzes the uncertainty in outdoor/indoor three-dimensional coordinate measures and point clouds (using Spherical Accuracy Standard (SAS) methods) for Eyes Map, a medium-cost tablet manufactured by e-Capture Research & Development Company, Merida, Spain. To achieve it, in outdoor tests, by means of this device, the coordinates of targets were measured from 1 to 6 m and cloud points were obtained. Subsequently, these were compared to the coordinates of the same targets measured by a Total Station. The Euclidean average distance error was 0.005-0.027 m for measurements by Photogrammetry and 0.013-0.021 m for the point clouds. All of them satisfy the tolerance for point cloud acquisition (0.051 m) according to the BIM Guide for 3D Imaging (General Services Administration); similar results are obtained in the indoor tests, with values of 0.022 m. In this paper, we establish the optimal distances for the observations in both, Photogrammetry and 3D Photomodeling modes (outdoor) and point out some working conditions to avoid in indoor environments. Finally, the authors discuss some recommendations for improving the performance and working methods of the device. PMID- 27669246 TI - Six-Port Based Interferometry for Precise Radar and Sensing Applications. AB - Microwave technology plays a more important role in modern industrial sensing applications. Pushed by the significant progress in monolithic microwave integrated circuit technology over the past decades, complex sensing systems operating in the microwave and even millimeter-wave range are available for reasonable costs combined with exquisite performance. In the context of industrial sensing, this stimulates new approaches for metrology based on microwave technology. An old measurement principle nearly forgotten over the years has recently gained more and more attention in both academia and industry: the six-port interferometer. This paper reviews the basic concept, investigates promising applications in remote, as well as contact-based sensing and compares the system with state-of-the-art metrology. The significant advantages will be discussed just as the limitations of the six-port architecture. Particular attention will be paid to impairment effects and non-ideal behavior, as well as compensation and linearization concepts. It will be shown that in application fields, like remote distance sensing, precise alignment measurements, as well as interferometrically-evaluated mechanical strain analysis, the six-port architecture delivers extraordinary measurement results combined with high measurement data update rates for reasonable system costs. This makes the six port architecture a promising candidate for industrial metrology. PMID- 27669247 TI - ReliefF-Based EEG Sensor Selection Methods for Emotion Recognition. AB - Electroencephalogram (EEG) signals recorded from sensor electrodes on the scalp can directly detect the brain dynamics in response to different emotional states. Emotion recognition from EEG signals has attracted broad attention, partly due to the rapid development of wearable computing and the needs of a more immersive human-computer interface (HCI) environment. To improve the recognition performance, multi-channel EEG signals are usually used. A large set of EEG sensor channels will add to the computational complexity and cause users inconvenience. ReliefF-based channel selection methods were systematically investigated for EEG-based emotion recognition on a database for emotion analysis using physiological signals (DEAP). Three strategies were employed to select the best channels in classifying four emotional states (joy, fear, sadness and relaxation). Furthermore, support vector machine (SVM) was used as a classifier to validate the performance of the channel selection results. The experimental results showed the effectiveness of our methods and the comparison with the similar strategies, based on the F-score, was given. Strategies to evaluate a channel as a unity gave better performance in channel reduction with an acceptable loss of accuracy. In the third strategy, after adjusting channels' weights according to their contribution to the classification accuracy, the number of channels was reduced to eight with a slight loss of accuracy (58.51% +/ 10.05% versus the best classification accuracy 59.13% +/- 11.00% using 19 channels). In addition, the study of selecting subject-independent channels, related to emotion processing, was also implemented. The sensors, selected subject-independently from frontal, parietal lobes, have been identified to provide more discriminative information associated with emotion processing, and are distributed symmetrically over the scalp, which is consistent with the existing literature. The results will make a contribution to the realization of a practical EEG-based emotion recognition system. PMID- 27669248 TI - A MoS2 Nanosheet-Based Fluorescence Biosensor for Simple and Quantitative Analysis of DNA Methylation. AB - MoS2 nanomaterial has unique properties, including innate affinity with ss-DNA and quenching ability for fluorescence dyes. Here, we present the development of a simple fluorescence biosensor based on water-soluble MoS2 nanosheets and restriction endonuclease BstUI for methylation analysis of p16 promoter. The biosensing platform exhibited excellent sensitivity in detecting DNA with a linear range of 100 pM~20 nM and a detection limit of 140 pM. More importantly, our method could distinguish as low as 1% difference in methylation level. Compared with previous methylation analysis, our design is both time saving and simple to operate, avoiding the limitations of PCR-based assays without compromising performance. PMID- 27669249 TI - Estimation of Energy Expenditure Using a Patch-Type Sensor Module with an Incremental Radial Basis Function Neural Network. AB - Conventionally, indirect calorimetry has been used to estimate oxygen consumption in an effort to accurately measure human body energy expenditure. However, calorimetry requires the subject to wear a mask that is neither convenient nor comfortable. The purpose of our study is to develop a patch-type sensor module with an embedded incremental radial basis function neural network (RBFNN) for estimating the energy expenditure. The sensor module contains one ECG electrode and a three-axis accelerometer, and can perform real-time heart rate (HR) and movement index (MI) monitoring. The embedded incremental network includes linear regression (LR) and RBFNN based on context-based fuzzy c-means (CFCM) clustering. This incremental network is constructed by building a collection of information granules through CFCM clustering that is guided by the distribution of error of the linear part of the LR model. PMID- 27669250 TI - An Online Dictionary Learning-Based Compressive Data Gathering Algorithm in Wireless Sensor Networks. AB - To adapt to sense signals of enormous diversities and dynamics, and to decrease the reconstruction errors caused by ambient noise, a novel online dictionary learning method-based compressive data gathering (ODL-CDG) algorithm is proposed. The proposed dictionary is learned from a two-stage iterative procedure, alternately changing between a sparse coding step and a dictionary update step. The self-coherence of the learned dictionary is introduced as a penalty term during the dictionary update procedure. The dictionary is also constrained with sparse structure. It's theoretically demonstrated that the sensing matrix satisfies the restricted isometry property (RIP) with high probability. In addition, the lower bound of necessary number of measurements for compressive sensing (CS) reconstruction is given. Simulation results show that the proposed ODL-CDG algorithm can enhance the recovery accuracy in the presence of noise, and reduce the energy consumption in comparison with other dictionary based data gathering methods. PMID- 27669251 TI - Strain Sharing Assessment in Woven Fiber Reinforced Concrete Beams Using Fiber Bragg Grating Sensors. AB - Embedded fiber Bragg grating sensors have been extensively used worldwide for health monitoring of smart structures. In civil engineering, they provide a powerful method for monitoring the performance of composite reinforcements used for concrete structure rehabilitation and retrofitting. This paper discusses the problem of investigating the strain transfer mechanism in composite strengthened concrete beams subjected to three-point bending tests. Fiber Bragg grating sensors were embedded both in the concrete tensioned surface and in the woven fiber reinforcement. It has been shown that, if interface decoupling occurs, strain in the concrete can be up to 3.8 times higher than that developed in the reinforcement. A zero friction slipping model was developed which fitted very well the experimental data. PMID- 27669252 TI - Indoor-Outdoor Detection Using a Smart Phone Sensor. AB - In the era of mobile internet, Location Based Services (LBS) have developed dramatically. Seamless Indoor and Outdoor Navigation and Localization (SNAL) has attracted a lot of attention. No single positioning technology was capable of meeting the various positioning requirements in different environments. Selecting different positioning techniques for different environments is an alternative method. Detecting the users' current environment is crucial for this technique. In this paper, we proposed to detect the indoor/outdoor environment automatically without high energy consumption. The basic idea was simple: we applied a machine learning algorithm to classify the neighboring Global System for Mobile (GSM) communication cellular base station's signal strength in different environments, and identified the users' current context by signal pattern recognition. We tested the algorithm in four different environments. The results showed that the proposed algorithm was capable of identifying open outdoors, semi-outdoors, light indoors and deep indoors environments with 100% accuracy using the signal strength of four nearby GSM stations. The required hardware and signal are widely available in our daily lives, implying its high compatibility and availability. PMID- 27669253 TI - Secure Nearest Neighbor Query on Crowd-Sensing Data. AB - Nearest neighbor queries are fundamental in location-based services, and secure nearest neighbor queries mainly focus on how to securely and quickly retrieve the nearest neighbor in the outsourced cloud server. However, the previous big data system structure has changed because of the crowd-sensing data. On the one hand, sensing data terminals as the data owner are numerous and mistrustful, while, on the other hand, in most cases, the terminals find it difficult to finish many safety operation due to computation and storage capability constraints. In light of they Multi Owners and Multi Users (MOMU) situation in the crowd-sensing data cloud environment, this paper presents a secure nearest neighbor query scheme based on the proxy server architecture, which is constructed by protocols of secure two-party computation and secure Voronoi diagram algorithm. It not only preserves the data confidentiality and query privacy but also effectively resists the collusion between the cloud server and the data owners or users. Finally, extensive theoretical and experimental evaluations are presented to show that our proposed scheme achieves a superior balance between the security and query performance compared to other schemes. PMID- 27669254 TI - A Geographical Heuristic Routing Protocol for VANETs. AB - Vehicular ad hoc networks (VANETs) leverage the communication system of Intelligent Transportation Systems (ITS). Recently, Delay-Tolerant Network (DTN) routing protocols have increased their popularity among the research community for being used in non-safety VANET applications and services like traffic reporting. Vehicular DTN protocols use geographical and local information to make forwarding decisions. However, current proposals only consider the selection of the best candidate based on a local-search. In this paper, we propose a generic Geographical Heuristic Routing (GHR) protocol that can be applied to any DTN geographical routing protocol that makes forwarding decisions hop by hop. GHR includes in its operation adaptations simulated annealing and Tabu-search meta heuristics, which have largely been used to improve local-search results in discrete optimization. We include a complete performance evaluation of GHR in a multi-hop VANET simulation scenario for a reporting service. Our study analyzes all of the meaningful configurations of GHR and offers a statistical analysis of our findings by means of MANOVA tests. Our results indicate that the use of a Tabu list contributes to improving the packet delivery ratio by around 5% to 10%. Moreover, if Tabu is used, then the simulated annealing routing strategy gets a better performance than the selection of the best node used with carry and forwarding (default operation). PMID- 27669255 TI - A Wireless and Batteryless Intelligent Carbon Monoxide Sensor. AB - Carbon monoxide (CO) poisoning from natural gas water heaters is a common household accident in Taiwan. We propose a wireless and batteryless intelligent CO sensor for improving the safety of operating natural gas water heaters. A micro-hydropower generator supplies power to a CO sensor without battery (COSWOB) (2.5 W at a flow rate of 4.2 L/min), and the power consumption of the COSWOB is only ~13 mW. The COSWOB monitors the CO concentration in ambient conditions around natural gas water heaters and transmits it to an intelligent gateway. When the CO level reaches a dangerous level, the COSWOB alarm sounds loudly. Meanwhile, the intelligent gateway also sends a trigger to activate Wi-Fi alarms and sends notifications to the mobile device through the Internet. Our strategy can warn people indoors and outdoors, thereby reducing CO poisoning accidents. We also believe that our technique not only can be used for home security but also can be used in industrial applications (for example, to monitor leak occurrence in a pipeline). PMID- 27669256 TI - A Low Power Digital Accumulation Technique for Digital-Domain CMOS TDI Image Sensor. AB - In this paper, an accumulation technique suitable for digital domain CMOS time delay integration (TDI) image sensors is proposed to reduce power consumption without degrading the rate of imaging. In terms of the slight variations of quantization codes among different pixel exposures towards the same object, the pixel array is divided into two groups: one is for coarse quantization of high bits only, and the other one is for fine quantization of low bits. Then, the complete quantization codes are composed of both results from the coarse-and-fine quantization. The equivalent operation comparably reduces the total required bit numbers of the quantization. In the 0.18 um CMOS process, two versions of 16 stage digital domain CMOS TDI image sensor chains based on a 10-bit successive approximate register (SAR) analog-to-digital converter (ADC), with and without the proposed technique, are designed. The simulation results show that the average power consumption of slices of the two versions are 6 . 47 * 10 - 8 J/line and 7 . 4 * 10 - 8 J/line, respectively. Meanwhile, the linearity of the two versions are 99.74% and 99.99%, respectively. PMID- 27669258 TI - Patterns-of-Life Aided Authentication. AB - Wireless Body Area Network (WBAN) applications have grown immensely in the past few years. However, security and privacy of the user are two major obstacles in their development. The complex and very sensitive nature of the body-mounted sensors means the traditional network layer security arrangements are not sufficient to employ their full potential, and novel solutions are necessary. In contrast, security methods based on physical layers tend to be more suitable and have simple requirements. The problem of initial trust needs to be addressed as a prelude to the physical layer security key arrangement. This paper proposes a patterns-of-life aided authentication model to solve this issue. The model employs the wireless channel fingerprint created by the user's behavior characterization. The performance of the proposed model is established through experimental measurements at 2.45 GHz. Experimental results show that high correlation values of 0.852 to 0.959 with the habitual action of the user in different scenarios can be used for auxiliary identity authentication, which is a scalable result for future studies. PMID- 27669257 TI - Characterization of Biosensors Based on Recombinant Glutamate Oxidase: Comparison of Crosslinking Agents in Terms of Enzyme Loading and Efficiency Parameters. AB - Amperometric l-glutamate (Glu) biosensors, based on both wild-type and a recombinant form of l-glutamate oxidase (GluOx), were designed and characterized in terms of enzyme-kinetic, sensitivity and stability parameters in attempts to fabricate a real-time Glu monitoring device suitable for future long-term detection of this amino acid in biological and other complex media. A comparison of the enzyme from these two sources showed that they were similar in terms of biosensor performance. Optimization of the loading of the polycationic stabilization agent, polyethyleneimine (PEI), was established before investigating a range of crosslinking agents under different conditions: glutaraldehyde (GA), polyethylene glycol (PEG), and polyethylene glycol diglycidyl ether (PEGDE). Whereas PEI-free biosensor designs lost most of their meager Glu sensitivity after one or two days, configurations with a 2:5 ratio of dip-evaporation applications of PEI(1%):GluOx(400 U/mL) displayed a 20-fold increase in their initial sensitivity, and a decay half-life extended to 10 days. All the crosslinkers studied had no effect on initial Glu sensitivity, but enhanced biosensor stability, provided the crosslinking procedure was carried out under well-defined conditions. The resulting biosensor design based on the recombinant enzyme deposited on a permselective layer of poly-(ortho phenylenediamine), PoPD/PEI2/GluOx5/PEGDE, displayed good sensitivity (LOD < 0.2 MUM), response time (t90% < 1 s) and stability over a 90-day period, making it an attractive candidate for future long-term monitoring of Glu concentration dynamics in complex media. PMID- 27669259 TI - Data Analytics for Smart Parking Applications. AB - We consider real-life smart parking systems where parking lot occupancy data are collected from field sensor devices and sent to backend servers for further processing and usage for applications. Our objective is to make these data useful to end users, such as parking managers, and, ultimately, to citizens. To this end, we concoct and validate an automated classification algorithm having two objectives: (1) outlier detection: to detect sensors with anomalous behavioral patterns, i.e., outliers; and (2) clustering: to group the parking sensors exhibiting similar patterns into distinct clusters. We first analyze the statistics of real parking data, obtaining suitable simulation models for parking traces. We then consider a simple classification algorithm based on the empirical complementary distribution function of occupancy times and show its limitations. Hence, we design a more sophisticated algorithm exploiting unsupervised learning techniques (self-organizing maps). These are tuned following a supervised approach using our trace generator and are compared against other clustering schemes, namely expectation maximization, k-means clustering and DBSCAN, considering six months of data from a real sensor deployment. Our approach is found to be superior in terms of classification accuracy, while also being capable of identifying all of the outliers in the dataset. PMID- 27669261 TI - An Online Gravity Modeling Method Applied for High Precision Free-INS. AB - For real-time solution of inertial navigation system (INS), the high-degree spherical harmonic gravity model (SHM) is not applicable because of its time and space complexity, in which traditional normal gravity model (NGM) has been the dominant technique for gravity compensation. In this paper, a two-dimensional second-order polynomial model is derived from SHM according to the approximate linear characteristic of regional disturbing potential. Firstly, deflections of vertical (DOVs) on dense grids are calculated with SHM in an external computer. And then, the polynomial coefficients are obtained using these DOVs. To achieve global navigation, the coefficients and applicable region of polynomial model are both updated synchronously in above computer. Compared with high-degree SHM, the polynomial model takes less storage and computational time at the expense of minor precision. Meanwhile, the model is more accurate than NGM. Finally, numerical test and INS experiment show that the proposed method outperforms traditional gravity models applied for high precision free-INS. PMID- 27669260 TI - Sensor Fusion and Smart Sensor in Sports and Biomedical Applications. AB - The following work presents an overview of smart sensors and sensor fusion targeted at biomedical applications and sports areas. In this work, the integration of these areas is demonstrated, promoting a reflection about techniques and applications to collect, quantify and qualify some physical variables associated with the human body. These techniques are presented in various biomedical and sports applications, which cover areas related to diagnostics, rehabilitation, physical monitoring, and the development of performance in athletes, among others. Although some applications are described in only one of two fields of study (biomedicine and sports), it is very likely that the same application fits in both, with small peculiarities or adaptations. To illustrate the contemporaneity of applications, an analysis of specialized papers published in the last six years has been made. In this context, the main characteristic of this review is to present the largest quantity of relevant examples of sensor fusion and smart sensors focusing on their utilization and proposals, without deeply addressing one specific system or technique, to the detriment of the others. PMID- 27669262 TI - Assessment of Receiver Signal Strength Sensing for Location Estimation Based on Fisher Information. AB - Currently there is almost ubiquitous availability of wireless signaling for data communications within commercial building complexes resulting in receiver signal strength (RSS) observables that are typically sufficient for generating viable location estimates of mobile wireless devices. However, while RSS observables are generally plentiful, achieving an accurate estimation of location is difficult due to several factors affecting the electromagnetic coupling between the mobile antenna and the building access points that are not modeled and hence contribute to the overall estimation uncertainty. Such uncertainty is typically mitigated with a moderate redundancy of RSS sensor observations in combination with other constraints imposed on the mobile trajectory. In this paper, the Fisher Information (FI) of a set of RSS sensor observations in the context of variables related to the mobile location is developed. This provides a practical method of determining the potential location accuracy for the given set of wireless signals available. Furthermore, the information value of individual RSS measurements can be quantified and the RSS observables weighted accordingly in estimation combining algorithms. The practical utility of using FI in this context was demonstrated experimentally with an extensive set of RSS measurements recorded in an office complex. The resulting deviation of the mobile location estimation based on application of weighted likelihood processing to the experimental RSS data was shown to agree closely with the Cramer Rao bound determined from the FI analysis. PMID- 27669265 TI - Micro-Doppler Signal Time-Frequency Algorithm Based on STFRFT. AB - This paper proposes a time-frequency algorithm based on short-time fractional order Fourier transformation (STFRFT) for identification of a complicated movement targets. This algorithm, consisting of a STFRFT order-changing and quick selection method, is effective in reducing the computation load. A multi-order STFRFT time-frequency algorithm is also developed that makes use of the time frequency feature of each micro-Doppler component signal. This algorithm improves the estimation accuracy of time-frequency curve fitting through multi-order matching. Finally, experiment data were used to demonstrate STFRFT's performance in micro-Doppler time-frequency analysis. The results validated the higher estimate accuracy of the proposed algorithm. It may be applied to an LFM (Linear frequency modulated) pulse radar, SAR (Synthetic aperture radar), or ISAR (Inverse synthetic aperture radar), for improving the probability of target recognition. PMID- 27669263 TI - Design and Evaluation of Novel Textile Wearable Systems for the Surveillance of Vital Signals. AB - This article addresses the design, development, and evaluation of T-shirt prototypes that embed novel textile sensors for the capture of cardio and respiratory signals. The sensors are connected through textile interconnects to either an embedded custom-designed data acquisition and transmission unit or to snap fastener terminals for connection to external monitoring devices. The performance of the T-shirt prototype is evaluated in terms of signal-to-noise ratio amplitude and signal interference caused by baseline wander and motion artefacts, through laboratory tests with subjects in standing and walking conditions. Performance tests were also conducted in a hospital environment using a T-shirt prototype connected to a commercial three-channel Holter monitoring device. The textile sensors and interconnects were realized with the assistance of an industrial six-needle digital embroidery tool and their resistance to wear addressed with normalized tests of laundering and abrasion. The performance of these wearable systems is discussed, and pathways and methods for their optimization are highlighted. PMID- 27669264 TI - A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface. AB - All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID- 27669266 TI - A Novel Zero Velocity Interval Detection Algorithm for Self-Contained Pedestrian Navigation System with Inertial Sensors. AB - Zero velocity update (ZUPT) plays an important role in pedestrian navigation algorithms with the premise that the zero velocity interval (ZVI) should be detected accurately and effectively. A novel adaptive ZVI detection algorithm based on a smoothed pseudo Wigner-Ville distribution to remove multiple frequencies intelligently (SPWVD-RMFI) is proposed in this paper. The novel algorithm adopts the SPWVD-RMFI method to extract the pedestrian gait frequency and to calculate the optimal ZVI detection threshold in real time by establishing the function relationships between the thresholds and the gait frequency; then, the adaptive adjustment of thresholds with gait frequency is realized and improves the ZVI detection precision. To put it into practice, a ZVI detection experiment is carried out; the result shows that compared with the traditional fixed threshold ZVI detection method, the adaptive ZVI detection algorithm can effectively reduce the false and missed detection rate of ZVI; this indicates that the novel algorithm has high detection precision and good robustness. Furthermore, pedestrian trajectory positioning experiments at different walking speeds are carried out to evaluate the influence of the novel algorithm on positioning precision. The results show that the ZVI detected by the adaptive ZVI detection algorithm for pedestrian trajectory calculation can achieve better performance. PMID- 27669267 TI - A Human Serum-Based Enzyme-Free Continuous Glucose Monitoring Technique Using a Needle-Type Bio-Layer Interference Sensor. AB - The incidence of diabetes is continually increasing, and by 2030, it is expected to have increased by 69% and 20% in underdeveloped and developed countries, respectively. Therefore, glucose sensors are likely to remain in high demand in medical device markets. For the current study, we developed a needle-type bio layer interference (BLI) sensor that can continuously monitor glucose levels. Using dialysis procedures, we were able to obtain hypoglycemic samples from commercial human serum. These dialysis-derived samples, alongside samples of normal human serum were used to evaluate the utility of the sensor for the detection of the clinical interest range of glucose concentrations (70-200 mg/dL), revealing high system performance for a wide glycemic state range (45-500 mg/dL). Reversibility and reproducibility were also tested over a range of time spans. Combined with existing BLI system technology, this sensor holds great promise for use as a wearable online continuous glucose monitoring system for patients in a hospital setting. PMID- 27669269 TI - Exploring Typical and Atypical Safety Climate Perceptions of Practitioners in the Repair, Maintenance, Minor Alteration and Addition (RMAA) Sector in Hong Kong. AB - The safety of repair, maintenance, minor alteration and addition (RMAA) work is an under-explored area. This study explored the typical and atypical safety climate perceptions of practitioners in the RMAA sector in Hong Kong, based on a self-administered questionnaire survey of 662 local practitioners in the industry. Profile analysis, via multidimensional scaling of the respondents' scores of three safety climate scales, identified one typical perception: high in management commitment to occupational health and safety (OHS) and employee involvement, low in applicability for safety rules and regulations, and low in responsibility for OHS. The respondents were clustered into typical and atypical perception groups according to their safety climate scores' match to the typical perception. A comparison of demographics between the two groups with logistic regression found that work level and direct employer significantly affect their classification. A multivariate analysis of variance of safety performance measures between the two groups indicated that the typical group had a significantly higher level of safety compliance than the atypical group, with no significant difference in safety participation or injury. The significance of this study lies in revealing the typical safety climate perception profile pattern of RMAA works and offering a new perspective of safety climate research. PMID- 27669268 TI - Marine Microbiological Enzymes: Studies with Multiple Strategies and Prospects. AB - Marine microorganisms produce a series of promising enzymes that have been widely used or are potentially valuable for our daily life. Both classic and newly developed biochemistry technologies have been broadly used to study marine and terrestrial microbiological enzymes. In this brief review, we provide a research update and prospects regarding regulatory mechanisms and related strategies of acyl-homoserine lactones (AHL) lactonase, which is an important but largely unexplored enzyme. We also detail the status and catalytic mechanism of the main types of polysaccharide-degrading enzymes that broadly exist among marine microorganisms but have been poorly explored. In order to facilitate understanding, the regulatory and synthetic biology strategies of terrestrial microorganisms are also mentioned in comparison. We anticipate that this review will provide an outline of multiple strategies for promising marine microbial enzymes and open new avenues for the exploration, engineering and application of various enzymes. PMID- 27669270 TI - Menopausal Age and Chronic Diseases in Elderly Women: A Cross-Sectional Study in Northeast China. AB - Many factors affect menopausal age, and early or late onset of menopause may be associated with many chronic health problems. However, limited data are available regarding this phenomenon in the Northeast China population. For this study, 2011 elderly women were selected as a sample from participants in a cross-sectional survey performed using stratified, clustered multistage, and random sampling methods. Early menopause was more prevalent in subjects born from 1943 to 1947 (OR = 1.708, 95% CI = 1.205, 2.420) and 1933 to 1937 (OR = 2.445, 95% CI: 1.525, 3.921) and in physical laborers (OR = 1.413, 95% CI = 1.021, 1.957). Women with less than nine years of education (OR = 0.515, 95% CI: 0.327, 0.812) and who were current smokers (OR = 0.577, 95% CI: 0.347, 0.959) were less likely to have late menopause. BMIs between 25 and 30 (OR = 1.565, 95% CI: 1.152, 2.125) and greater than 30 (OR = 2.440, 95% CI: 1.482, 4.016) were associated with later menopausal age. Late menopause was positively associated with diabetes (OR = 1.611, 95% CI: 1.142, 2.274) but protective against chronic gastroenteritis/peptic ulcers (OR = 0.533, 95% CI: 0.333, 0.855). Results showed that (1) Being born in an earlier year, having a lower education, and engaging in physical labor were associated with an earlier menopausal age, while a higher BMI was associated with a later menopausal age; and that (2) menopausal age was associated with diabetes and gastroenteritis in elderly women living in Northeast China. PMID- 27669272 TI - Socioeconomic Drivers of PM2.5 in the Accumulation Phase of Air Pollution Episodes in the Yangtze River Delta of China. AB - Recent studies in PM2.5 sources show that anthropogenic emissions are the main contributors to haze pollution. Due to their essential roles in establishing policies for improving air quality, socioeconomic drivers of PM2.5 levels have attracted increasing attention. Unlike previous studies focusing on the annual PM2.5 concentration (Cyear), this paper focuses on the accumulation phase of PM2.5 during the pollution episode (PMAE) in the Yangtze River Delta in China. This paper mainly explores the spatial variations of PMAE and its links to the socioeconomic factors using a geographical detector and simple linear regression. The results indicated that PM2.5 was more likely to accumulate in more developed cities, such as Nanjing and Shanghai. Compared with Cyear, PMAE was more sensitive to socioeconomic impacts. Among the twelve indicators chosen for this study, population density was an especially critical factor that could affect the accumulation of PM2.5 dramatically and accounted for the regional difference. A 1% increase in population density could cause a 0.167% rise in the maximal increment and a 0.214% rise in the daily increase rate of PM2.5. Additionally, industry, energy consumption, and vehicles were also significantly associated with PM2.5 accumulation. These conclusions could serve to remediate the severe PM2.5 pollution in China. PMID- 27669271 TI - Acetamiprid Accumulates in Different Amounts in Murine Brain Regions. AB - Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of alpha7, alpha4, and beta2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), beta2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure. PMID- 27669273 TI - Time Effectiveness of Ultraviolet C Light (UVC) Emitted by Light Emitting Diodes (LEDs) in Reducing Stethoscope Contamination. AB - Today it is well demonstrated that stethoscopes can be as contaminated as hands, which are a recognized source of Health-Care Associated Infections (HCAIs). Ultraviolet C (UVC) light has proven disinfection capacity and the innovative UVC technology of Light Emitting Diode (LED) shows several potential benefits. To verify whether the use of UVC LEDs is effective and reliable in stethoscope membrane disinfection after prolonged use, a pre-post intervention study was conducted. A total of 1668 five-minute cycles were performed on two UVC LEDs to simulate their use; thereafter, their disinfection capacity was tested on stethoscope membranes used on a previously auscultated volunteer. Then, a further 1249 cycles were run and finally the LEDs were tested to assess performance in reducing experimental contamination by Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli on the stethoscope membrane. Baseline volunteer contamination identified 104 Colony Forming Units (CFUs) while treated Petri dishes had 12 and 15 CFUs (p < 0.001). Statistically significant differences (p < 0.001) were also found relating to the reduction of specific bacteria: in particular, after treatment no CFU were observed for S. aureus and E. coli. UVC LEDs demonstrated the capacity to maintain high levels of disinfection after more than 240 h of use and they were effective against common microorganisms that are causative agents of HCAIs. PMID- 27669274 TI - Trace Elements Contamination and Human Health Risk Assessment in Drinking Water from the Agricultural and Pastoral Areas of Bay County, Xinjiang, China. AB - Tap water samples were collected from 180 families in four agricultural (KYR: Keyir, KRW: Kariwak, YTR: Yatur, DW: Dawanqi) and two pastoral areas (B: Bulong and Y: Yangchang) in Bay County, Xinjiang, China, and levels of seven trace elements (Cd, Cr, As Ni, Pb, Zn, Se) were analyzed using inductively-coupled plasma mass spectrometry (ICP-MS) to assess potential health risks. Remarkable spatial variations of contamination were observed. Overall, the health risk was more severe for carcinogenic versus non-carcinogenic pollutants due to heavy metal. The risk index was greater for children overall (Cr > As > Cd and Zn > Se for carcinogenic and non-carcinogenic elements, respectively). The total risk index was greater in agricultural areas (DW > KYR > YTR > KRW > B > Y). Total risk indices were greater where well water was the source versus fountain water; for the latter, the total health risk index was greater versus glacier water. Main health risk factors were Cr and As in DW, KYR, YTR, KRW, and B, and Zn, Cr, and As in the Y region. Overall, total trace element-induced health risk (including for DW adults) was higher than acceptable (10(-6)) and lower than priority risk levels (10(-4)) (KYR, YTR, KRW, Y, and B). For DW children, total health risk reached 1.08 * 10(-4), higher than acceptable and priority risk levels (10(-4)). PMID- 27669275 TI - Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers. AB - MicroRNA biosynthesis genes can affect the regulatory effect of global microRNAs to target mRNA and hence influence the genesis and development of human cancer. Here, we selected five single nucleotide polymorphisms (SNPs) (rs7813, rs2740349, rs2291778, rs910924, rs595961) in two key microRNA biosynthesis genes (GEMIN4 and AGO1) and systematically evaluated the association between these SNPs, the gene environment interaction and lung cancer risk. To control the impact of cigarette smoking on lung cancer, we recruited Chinese female non-smokers for the study. The total number of lung cancer cases and cancer-free controls were 473 and 395 in the case-control study. Four SNPs showed statistically significant associations with lung cancer risk. After Bonferroni correction, rs7813 and rs595961 were evidently still associated with lung cancer risk. In the stratified analysis, our results revealed that all five SNPs were associated with the risk of lung adenocarcinoma; after Bonferroni correction, significant association was maintained for rs7813, rs910924 and rs595961. Haplotype analysis showed GEMIN4 haplotype C-A-G-T was a protective haplotype for lung cancer. In the combined unfavorable genotype analysis, with the increasing number of unfavorable genotypes, a progressively increased gene-dose effect was observed in lung adenocarcinoma. We also found that individuals exposed to cooking oil fumes showed a relatively high risk of lung cancer, but no interactions were found between cooking oil fume exposure or passive smoking exposure with these SNPs, either on an additive scale or a multiplicative scale. Overall, this is the first study showing that rs7813 and rs595961 could be meaningful as genetic markers for lung cancer risk. PMID- 27669276 TI - Pesticide Residues on Three Cut Flower Species and Potential Exposure of Florists in Belgium. AB - In order to assess the prevalence of pesticide contamination and the risk of florists' exposure when handling cut flowers, sampling and analysis of 90 bouquets of the most commonly sold cut flowers in Belgium (50 bouquets of roses; 20 of gerberas, and 20 of chrysanthemums) were carried out. The bouquets were collected from 50 florists located in the seven largest cities of Belgium (Antwerp, Brussels, Charleroi, Ghent, Leuven, Liege, and Namur) and from five supermarkets located in the different regions. To have a better understanding of the route of exposure and professional practices a questionnaire was also addressed to a group of 25 florists who volunteered to take part in the survey. All florists were interviewed individually when collecting the questionnaire. The residual pesticide deposit values on cut flowers were determined in an accredited laboratory using a multi-residue (QuEChERS Quick Easy Cheap Effective Rugged Safe) method and a combination of gas chromatography (GC) and liquid chormatograhphy (LC) analysis. A total of 107 active substances were detected from all samples; i.e., an average of about 10 active substances per bouquet. The most severely contaminated bouquet accumulated a total concentration of residues up to 97 mg/kg. Results show that roses are the most contaminated cut flowers; with an average of 14 substances detected per sample and a total concentration per rose sample of 26 mg/kg. Some active substances present an acute toxicity (acephate, methiocarb, monocrotophos, methomyl, deltamethrin, etc.) and exposure can generate a direct effect on the nervous system of florists. Nevertheless, fungicides (dodemorph, propamocarb, and procymidone) were the most frequently detected in samples and had the highest maximum concentrations out of all the active substances analysed. Dodemorph was the most frequently detected substance with the highest maximum concentration (41.9 mg/kg) measured in the rose samples. It appears from the survey that, despite being exposed to high deposits of residues, florists usually do not protect themselves from contact with residues even if they spend several hours handling cut flowers and preparing bouquets (from 2 to 6 h/day, depending on the time of year and/or selling periods) daily. Bad habits (eating, drinking, or smoking at work) and absence of personal protective equipment of most florists also increase the risk of contact with pesticide residues. PMID- 27669277 TI - The Use of Exenatide in Managing Markers of Cardiovascular Risk in Patients with Type 2 Diabetes: A Systematic Review. AB - OBJECTIVE: This review examines the use of exenatide twice daily in managing changes in markers of cardiovascular risk in patients with type 2 diabetes. BACKGROUND: Type 2 diabetes is a progressive metabolic disorder, which results from defects in insulin secretion and/or insulin action leading to chronic hyperglycaemia and associated cardiovascular complications. Despite the use of diet, exercise, oral antihyperglycaemic agents and insulin, the progressive nature of the condition means that the levels of the preventive and treatment measures would have to be increased and/or new therapies have to be developed in order to address the long term impact of type 2 diabetes. The advent of exenatide, a glucagon-like peptide-1 receptor agonist provides a useful basis for managing type 2 diabetes and related cardiovascular complications without the side effects of regular diabetes therapies. However, exenatide twice daily is often used in combination with other therapies, although the mechanism of exenatide in managing diabetes and and associated cardiovascular risks and complications remain complex and still evolving. METHOD: A range of databases including EBSCOhost online research database were used to access articles based on PICO (Population, Interventions, Comparative Interventions, Outcomes) framework and Boolean operators. RESULTS: Eleven randomised controlled studies which met the inclusion criteria were selected for this review. Nine of the eleven studies showed significant decrease in body weight among participants in the exenatide group compared with placebo or control group while the other two studies did not report statistically significant differences in body weight. In adition, all the studies showed statistically significant decrease in glycated haemoglobin (HbA1c) in the exenatide group compared to controls except in one study. In the present review, the seven studies, which looked at the effect of exenatide twice daily on lipid profile, did not find any significant difference between the exenatide group and the control group except for High density lipoprotein-cholesterol in two of the studies. However, statistically significant decrease was observed between exenatide group and controls with respect to blood pressure (systolic and/or diastolic) in these studies. DISCUSSION: It would appear that exenatide is more effective in reducing body weight in patients with type 2 diabetes when used in combination with metformin than when used alone or in combination with thiazolidinedione. The findings of this review would suggest that exenatide twice daily may be useful in managing cardiovascular risks and complications by reducing body weight, HbA1c and blood pressure. PMID- 27669278 TI - The Possibility of Decreasing 50-Hz Electric Field Exposure near 400-kV Power Lines with Arc Flash Personal Protective Equipment. AB - Various guidelines for the protection of human beings against possible adverse effects resulting from exposure to electromagnetic fields (EMFs) have been published with a view towards continual improvement; therefore, decreasing exposure is an important research area. The aim of this study was to investigate the possibility of decreasing electric field exposure with arc flash rated personal protective equipment (PPE), which in this case was a set of coveralls, and to compare the measurement results to calculations using the helmet-mask measuring system. We collected the data under a 400-kV power line. The test person stood on isolated aluminum paper, and the current between the ground and the aluminum paper was measured. When the test subject wore the arc flash PPE, the current to the ground was only 9.5% of the current measured when wearing normal clothes, which represents a clear decrease in exposure. PMID- 27669279 TI - Estimation of the Disease Burden Attributable to 11 Risk Factors in Hubei Province, China: A Comparative Risk Assessment. AB - In order to estimate the health losses caused by common risk factors in the Hubei province, China, we calculated the deaths and disability-adjusted life years (DALYs) attributable to 11 risk factors. We estimated the exposure distributions of risk factors in Hubei Province in 2013 from the monitoring system on chronic disease and related risk factors, combined with relative risk (RR) in order to calculate the population attributable fraction. Deaths and DALYs attributed to the selected risk factors were then estimated together with cause-specific deaths and DALYs. In total, 53.39% of the total deaths and 36.23% of the total DALYs in Hubei were a result of the 11 selected risk factors. The top five risk factors were high blood pressure, smoking, high body mass index, diet low in fruits and alcohol use, accounting for 14.68%, 12.57%, 6.03%, 3.90% and 3.19% of total deaths, respectively, and 9.41%, 7.22%, 4.42%, 2.51% and 2.44% of total DALYs, respectively. These risk factors, especially high blood pressure, smoking and high body mass index, significantly influenced quality of life, causing a large number of deaths and DALYs. The burden of chronic disease could be substantially reduced if these risk factors were effectively controlled, which would allow people to enjoy healthier lives. PMID- 27669280 TI - Effects of Particulate Matter and Its Chemical Constituents on Elderly Hospital Admissions Due to Circulatory and Respiratory Diseases. AB - Various fractions of particulate matter have been associated with increased mortality and morbidity. The purpose of our study is to analyze the associations between concentrations of PM2.5, PM2.5-10, PM10 and their chemical constituents (soluble ions) with hospital admissions due to circulatory and respiratory diseases among the elderly in a medium-sized city in Brazil. A time series study was conducted using Poisson regression with generalized additive models adjusted for confounders. Statistically significant associations were identified between PM10 and PM2.5-10 and respiratory diseases. Risks of hospitalization increased by 23.5% (95% CI: 13.5; 34.3) and 12.8% (95% CI: 6.0; 20.0) per 10 MUg/m3 of PM2.5 10 and PM10, respectively. PM2.5 exhibited a significant association with circulatory system diseases, with the risk of hospitalization increasing by 19.6% (95% CI: 6.4; 34.6) per 10 MUg/m3. Regarding the chemical species; SO4(2-), NO3( ), NH4+ and K+ exhibited specific patterns of risk, relative to the investigated outcomes. Overall, SO4(2-) in PM2.5-10 and K+ in PM2.5 were associated with increased risk of hospital admissions due to both types of diseases. The results agree with evidence indicating that the risks for different health outcomes vary in relation to the fractions and chemical composition of PM10. Thus, PM10 speciation studies may contribute to the establishment of more selective pollution control policies. PMID- 27669281 TI - Relationship between Methyl Tertiary Butyl Ether Exposure and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Petrol Station Attendants in Southern China. AB - Methyl tertiary butyl ether (MTBE)-A well known gasoline additive substituting for lead alkyls-causes lipid disorders and liver dysfunctions in animal models. However, whether MTBE exposure is a risk factor for non-alcoholic fatty liver disease (NAFLD) remains uncertain. We evaluate the possible relationship between MTBE exposure and the prevalence of NAFLD among 71 petrol station attendants in southern China. The personal exposure concentrations of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS. NAFLD was diagnosed by using abdominal ultrasonography according to the guidelines for the diagnosis and treatment of NAFLD suggested by the Chinese Hepatology Association. Demographic and clinical characteristics potentially associated with NAFLD were investigated. Mutivariate logistic regression analysis was applied to measure odds ratios and 95% confidence intervals (CI). The result showed that the total prevalence of NAFLD was 15.49% (11/71) among the study subjects. The average exposure concentrations of MTBE were 292.98 +/- 154.90 MUg/m3 and 286.64 +/- 122.28 MUg/m3 in NAFLD and non-NAFLD groups, respectively, and there was no statistically significant difference between them (p > 0.05). After adjusting for age, gender, physical exercise, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), white blood cell (WBC), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), the odds ratios were 1.31 (95% CI: 0.85-1.54; p > 0.05), 1.14 (95% CI: 0.81-1.32; p > 0.05), 1.52 (95% CI: 0.93-1.61; p > 0.05) in the groups (including men and women) with exposure concentrations of MTBE of 100-200 MUg/m3, 200-300 MUg/m3, and >=300 MUg/m3, respectively, as compared to the group (including men and women) <=100 MUg/m3. Our investigation indicates that exposure to MTBE does not seem to be a significant risk factor for the prevalence of NAFLD among petrol station attendants in southern China. PMID- 27669282 TI - Lessons and Perspectives from a 25-Year Bioelectromagnetics Research Program. AB - The question of whether electromagnetic fields from electric power or telecommunications systems can be linked unequivocally to health detriments has occupied scientific research endeavors for nearly half a century. For 25 years, the bioelectromagnetic research group at Swinburne University in Melbourne, Australia, has pursued a series of investigations with relevant endpoints, such as neurophysiological and neuropsychological effects, cell calcium level changes, proliferation, and genotoxic effects. Most have shown no significant changes due to fields, however, in some pilot studies significant changes were revealed, but in most cases these were not replicated in follow-up studies. This highlights a feature of this research area, generally; the unambiguous identification of small changes in noisy data where the understanding of possible interaction mechanisms is lacking. On the other hand, mathematical modelling studies, particularly with respect to fields near metallic implants, in workers exposed to fields in harsh environmental conditions and at very high frequencies (THz), continue to add to the expanding knowledge database on the characteristics of the complex electromagnetic environment we live in today. PMID- 27669284 TI - The Health, Enlightenment, Awareness, and Living (HEAL) Intervention: Outcome of an HIV and Hepatitis B and C Risk Reduction Intervention. AB - African American women have among the highest HIV/AIDS and hepatitis B and C incidence rates in the United States, especially among those homeless or incarcerated. The objective of this study was to evaluate the Health Enlightenment, Awareness and Living Intervention, designed to decrease HIV/AIDS, hepatitis and related risky behaviors. The thirteen-session intervention was implemented among homeless and formerly incarcerated low-income African American women, ages 18 to 55, in Atlanta, Georgia from 2006 to 2010. A single group repeated measures study design was employed and consisted of a pre-test (n = 355) group, an immediate post-test (n = 228) group with a response rate of 64%, and a six-month follow up (n = 110) group with response rate of 48%, completing a 135 item survey. Paired-sample t-tests, McNemar tests, and repeated measures ANOVA were applied to compare survey results. Participants demonstrated statistically significant increases in hepatitis B and C knowledge over time (p < 0.001). Statistically significant decreases were also reported for unprotected sex in exchange for money, drugs or shelter (p = 0.008), and sex under the influence of drugs or alcohol (p < 0.001). Reported substance use decreased with statistical significance for alcohol (p = 0.011), marijuana (p = 0.011), illegal drugs (p = 0.002), and crack/cocaine (p = 0.003). Findings broaden the evidence base related to the effectiveness of HIV/AIDS and hepatitis risk reduction interventions designed for homeless and previously incarcerated African American women. PMID- 27669283 TI - First Trimester Phthalate Exposure and Infant Birth Weight in the Infant Development and Environment Study. AB - Phthalate exposure is widespread among pregnant women but whether it is related to fetal growth and birth weight remains to be determined. We examined whether first trimester prenatal phthalate exposure was associated with birth weight in a pregnancy cohort study. We recruited first trimester pregnant women from 2010 2012 from four centers and analyzed mother/infant dyads who had complete urinary phthalate and birth record data (N = 753). We conducted multiple linear regression to examine if prenatal log specific gravity adjusted urinary phthalate exposure was related to birthweight in term and preterm (<=37 weeks) infants, stratified by sex. We observed a significant association between mono carboxy isononyl phthalate (MCOP) exposure and increased birthweight in term males, 0.13 kg (95% CI 0.03, 0.23). In preterm infants, we observed a 0.49 kg (95% CI 0.09, 0.89) increase in birthweight in relation to a one log unit change in the sum of di-ethylhexyl phthalate (DEHP) metabolite concentrations in females (N = 33). In summary, we observed few associations between prenatal phthalate exposure and birthweight. Positive associations may be attributable to unresolved confounding in term infants and limited sample size in preterm infants. PMID- 27669285 TI - Prevalence of Methicillin-Resistant Staphylococcus aureus and Other Staphylococcus Species in Raw Meat Samples Intended for Human Consumption in Benin City, Nigeria: Implications for Public Health. AB - The present study was designed to characterize methicillin-resistant staphylococci from raw meat. A total of 126 meat samples were obtained from open markets between February and April, 2015. Antimicrobial susceptibility testing was carried out using the disc diffusion method. Molecular profiling was conducted using 16S rRNA, mecA, nuc, and PVL gene signatures were detected by polymerase chain reaction assay. Fifty isolates of methicillin-resistant Staphylococcus spp. were detected in 26 (52%) pork, 14 (28%) beef and 10 (20%) chicken samples. The staphylococcal isolates were identified through partial 16S ribosomal ribonucleic acid (16S rRNA) nucleotide sequencing, and BLAST analysis of the gene sequence revealed 98%-100% staphylococcal similarity. All isolates from beef and chicken samples amplified the mecA gene, while 100% of the MRSA isolates amplified the PVL gene. The multidrug resistance profile (resistant to >=1 antimicrobial agent in >=3 classes of antimicrobial agents) of the staphylococcal isolates showed that 7 isolates were resistant to methicillin, penicillin, clindamycin, chloramphenicol, trimethoprim-sulfamethoxazole, kanamycin, amoxicillin, cloxacillin, erythromycin, vancomycin, and gentamycin. There was a significant regression effect from the multidrug-resistant profile on the number of isolates (p < 0.05) suggesting a consequence of the dissemination of resistant strains within bacterial populations. The findings of the present study indicate that raw meats in the Benin metropolis were possibly contaminated with pathogenic and multi-drug resistant staphylococci strains and therefore could constitute a risk to public health communities. PMID- 27669286 TI - Mechanistic Study of Common Non-Nucleoside Reverse Transcriptase Inhibitor Resistant Mutations with K103N and Y181C Substitutions. AB - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a mainstay of therapy for human immunodeficiency type 1 virus (HIV-1) infections. However, their effectiveness can be hampered by the emergence of resistant mutations. To aid in designing effective NNRTIs against the resistant mutants, it is important to understand the resistance mechanism of the mutations. Here, we investigate the mechanism of the two most prevalent NNRTI-associated mutations with K103N or Y181C substitution. Virus and reverse transcriptase (RT) with K103N/Y188F, K103A, or K103E substitutions and with Y181F, Y188F, or Y181F/Y188F substitutions were employed to study the resistance mechanism of the K103N and Y181C mutants, respectively. Results showed that the virus and RT with K103N/Y188F substitutions displayed similar resistance levels to the virus and RT with K103N substitution versus NNRTIs. Virus and RT containing Y181F, Y188F, or Y181F/Y188F substitution exhibited either enhanced or similar susceptibility to NNRTIs compared with the wild type (WT) virus. These results suggest that the hydrogen bond between N103 and Y188 may not play an important role in the resistance of the K103N variant to NNRTIs. Furthermore, the results from the studies with the Y181 or Y188 variant provide the direct evidence that aromatic pi-pi stacking plays a crucial role in the binding of NNRTIs to RT. PMID- 27669287 TI - Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes. AB - Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress-associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN. PMID- 27669288 TI - Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury. AB - (1) BACKGROUND: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) METHODS: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) RESULTS: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) CONCLUSION: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each other. PMID- 27669289 TI - Using Two Different Approaches to Assess Dietary Patterns: Hypothesis-Driven and Data-Driven Analysis. AB - The use of dietary patterns to assess dietary intake has become increasingly common in nutritional epidemiology studies due to the complexity and multidimensionality of the diet. Currently, two main approaches have been widely used to assess dietary patterns: data-driven and hypothesis-driven analysis. Since the methods explore different angles of dietary intake, using both approaches simultaneously might yield complementary and useful information; thus, we aimed to use both approaches to gain knowledge of adolescents' dietary patterns. Food intake from a cross-sectional survey with 295 adolescents was assessed by 24 h dietary recall (24HR). In hypothesis-driven analysis, based on the American National Cancer Institute method, the usual intake of Brazilian Healthy Eating Index Revised components were estimated. In the data-driven approach, the usual intake of foods/food groups was estimated by the Multiple Source Method. In the results, hypothesis-driven analysis showed low scores for Whole grains, Total vegetables, Total fruit and Whole fruits), while, in data driven analysis, fruits and whole grains were not presented in any pattern. High intakes of sodium, fats and sugars were observed in hypothesis-driven analysis with low total scores for Sodium, Saturated fat and SoFAA (calories from solid fat, alcohol and added sugar) components in agreement, while the data-driven approach showed the intake of several foods/food groups rich in these nutrients, such as butter/margarine, cookies, chocolate powder, whole milk, cheese, processed meat/cold cuts and candies. In this study, using both approaches at the same time provided consistent and complementary information with regard to assessing the overall dietary habits that will be important in order to drive public health programs, and improve their efficiency to monitor and evaluate the dietary patterns of populations. PMID- 27669290 TI - Can Parenting Practices Explain the Differences in Beverage Intake According to Socio-Economic Status: The Toybox-Study. AB - Previous research indicated that preschoolers of lower socioeconomic status (SES) consume less healthy beverages than high SES preschoolers. The purpose of this study is to investigate the mediating role of parenting practices in the relationship between SES and plain water, soft drink and prepacked fruit juice (FJ) consumption in European preschoolers. Parents/caregivers of 3.5 to 5.5 years old (n = 6776) recruited through kindergartens in six European countries within the ToyBox-study completed questionnaires on socio-demographics, parenting practices and a food frequency questionnaire. Availability of sugared beverages and plain water, permissiveness towards sugared beverages and lack of self efficacy showed a mediating effect on SES-differences in all three beverages. Rewarding with sugared beverages significantly mediated SES-differences for both plain water and prepacked FJ. Encouragement to drink plain water and awareness significantly mediated SES-differences for, respectively, plain water and prepacked FJ consumption. Avoiding negative modelling did not mediate any associations. Overall, lower SES preschoolers were more likely to be confronted with lower levels of favourable and higher levels of unfavourable parenting practices, which may lead to higher sugared beverage and lower plain water consumption. The current study highlights the importance of parenting practices in explaining the relation between SES and both healthy and unhealthy beverage consumption. PMID- 27669291 TI - Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia. AB - Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20-58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10-20/20-30/>=30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (-2.3 ng/mL; 95% CI: 4.1, -5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar. PMID- 27669293 TI - Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats. AB - Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor gamma (PPARgamma) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARgamma expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID- 27669292 TI - YAP Inhibition by Resveratrol via Activation of AMPK Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine. AB - Resveratrol, a natural polyphenol present in most plants, inhibits the growth of numerous cancers both in vitro and in vivo. Aberrant expression of YAP has been reported to activate multiple growth-regulatory pathways and confer anti apoptotic abilities to many cancer cells. However, the role of resveratrol in YES activated protein (YAP) expression and that of YAP in pancreatic cancer cells' response to gemcitabine resistance remain elusive. In this study, we found that resveratrol suppressed the proliferation and cloning ability and induced the apoptosis of pancreatic cancer cells. These multiple biological effects might result from the activation of AMP-activation protein kinase (AMPK) (Thr172) and, thus, the induction of YAP cytoplasmic retention, Ser127 phosphorylation, and the inhibition of YAP transcriptional activity by resveratrol. YAP silencing by siRNA or resveratrol enhanced the sensitivity of gemcitabine in pancreatic cancer cells. Taken together, these findings demonstrate that resveratrol could increase the sensitivity of pancreatic cancer cells to gemcitabine by inhibiting YAP expression. More importantly, our work reveals that resveratrol is a potential anticancer agent for the treatment of pancreatic cancer, and YAP may serve as a promising target for sensitizing pancreatic cancer cells to chemotherapy. PMID- 27669295 TI - Parental Encouragement of Healthy Lifestyles for Their Children and Personally Caring about Healthy Lifestyles Is Positively Associated with Children Using Vitamin D Supplements. AB - Supplement users have better vitamin D status, and parenting is key to promoting a child's healthy behaviours. We examined the association of parental encouragement of and caring about healthy lifestyles with children's use of vitamin D supplements and multivitamins. A provincially representative sample of grade 5 students (n = 2686; 10-11 years) and their parents across the province of Alberta, Canada, was surveyed in 2014. Students were asked about use of multivitamins and/or vitamin D supplements. Parents were asked whether they cared about and encouraged healthy lifestyles. Mixed effect multiple logistic regression identified the association of parental responses with children's use of supplements; 29% and 54% of children took vitamin D supplements and multivitamins, respectively. They were more likely to take vitamin D supplements if their parents cared 'very much' vs. 'not at all/a little bit' about eating healthy foods (OR = 1.43; 95% CI = 1.08, 1.89), cared 'quite a lot' (OR = 1.55; 95% CI = 1.17, 2.04) and 'very much' (OR = 1.67; 95% CI = 1.26, 2.21) vs. 'not at all/a little bit' about physical activity, and encouraged 'very much' vs. 'not at all/a little bit' their children to eat healthy foods (OR = 1.51; 95% CI = 1.05, 2.17). Children whose parents personally cared for eating healthy foods were more likely to take multivitamins ('quite a lot' and 'very much' compared to 'not at all/a little bit' (OR = 1.60; 95% CI = 1.13, 2.28 and OR = 1.46; 95% CI = 1.04, 2.06, respectively). Education and parental encouragement of healthy lifestyles should be part of the public health initiatives to promote supplementation of vitamin D among children. PMID- 27669294 TI - Triceps and Subscapular Skinfold Thickness Percentiles and Cut-Offs for Overweight and Obesity in a Population-Based Sample of Schoolchildren and Adolescents in Bogota, Colombia. AB - The assessment of skinfold thickness is an objective measure of adiposity. The aims of this study were to establish Colombian smoothed centile charts and LMS L (Box-Cox transformation), M (median), and S (coefficient of variation) tables for triceps, subscapular, and triceps + subscapular skinfolds; appropriate cut-offs were selected using receiver operating characteristic (ROC) analysis based on a population-based sample of children and adolescents in Bogota, Colombia. A cross sectional study was conducted in 9618 children and adolescents (55.7% girls; age range of 9-17.9 years). Triceps and subscapular skinfold measurements were obtained using standardized methods. We calculated the triceps + subscapular skinfold (T + SS) sum. Smoothed percentile curves for triceps and subscapular skinfold thickness were derived using the LMS method. ROC curve analyses were used to evaluate the optimal cut-off point of skinfold thickness for overweight and obesity, based on the International Obesity Task Force definitions. Subscapular and triceps skinfolds and T + SS were significantly higher in girls than in boys (p < 0.001). The ROC analysis showed that subscapular and triceps skinfolds and T + SS have a high discriminatory power in the identification of overweight and obesity in the sample population in this study. Our results provide sex- and age-specific normative reference standards for skinfold thickness values from a population from Bogota, Colombia. PMID- 27669296 TI - Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats. AB - Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX) surgery (n = 12/diet). The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint) using micro-computed tomography (MUCT) at a resolution of 9 MUm. As expected, OVX significantly reduced percent bone volume (BV/TV), connectivity density (Conn. D.), trabecular number (Tb. N.), and increased trabecular separation (Tb. Sp.) compared to SHAM rats (p < 0.001). However, post hoc analysis revealed these differences were present in rats fed menhaden oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats. PMID- 27669297 TI - Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice. AB - Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR). Current therapeutic options for the management of asthma include inhaled corticosteroids and beta2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2), one of the major components of bee venom (BV), to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA) on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30. The infiltration of immune cells, such as Th2 cytokines in the lungs, and the lung histology, were assessed in the OVA-challenged mice in the presence and absence of an intratracheal administration of bvPLA2. We showed that the intratracheal administration of bvPLA2 markedly suppressed the OVA-induced allergic airway inflammation by reducing AHR, overall area of inflammation, and goblet cell hyperplasia. Furthermore, the suppression was associated with a significant decrease in the production of Th2 cytokines, such as IL-4, IL-5, and IL-13, and a reduction in the number of total cells, including eosinophils, macrophages, and neutrophils in the airway. PMID- 27669298 TI - Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells. AB - Deoxynivalenol (DON) is a widespread trichothecene mycotoxin that commonly contaminates cereal crops and has various toxic effects in animals and humans. DON primarily targets the gastrointestinal tract, the first barrier against ingested food contaminants. In this study, an isobaric tag for relative and absolute quantitation (iTRAQ)-based phosphoproteomic approach was employed to elucidate the molecular mechanisms underlying DON-mediated intestinal toxicity in porcine epithelial cells (IPEC-J2) exposed to 20 MUM DON for 60 min. There were 4153 unique phosphopeptides, representing 389 phosphorylation sites, detected in 1821 phosphoproteins. We found that 289 phosphopeptides corresponding to 255 phosphoproteins were differentially phosphorylated in response to DON. Comprehensive Gene Ontology (GO) analysis combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that, in addition to previously well-characterized mitogen-activated protein kinase (MAPK) signaling, DON exposure altered phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase/signal transducer, and activator of transcription (JAK/STAT) pathways. These pathways are involved in a wide range of biological processes, including apoptosis, the intestinal barrier, intestinal inflammation, and the intestinal absorption of glucose. DON-induced changes are likely to contribute to the intestinal dysfunction. Overall, identification of relevant signaling pathways yielded new insights into the molecular mechanisms underlying DON-induced intestinal toxicity, and might help in the development of improved mechanism based risk assessments in animals and humans. PMID- 27669299 TI - Vasoactivity and Vasoconstriction Changes in Cattle Related to Time off Toxic Endophyte-Infected Tall Fescue. AB - Previous research has indicated that serotonergic and alpha-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichloe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture. In Experiment 1, lateral saphenous vein biopsies were conducted on 21 predominantly Angus steers (357 +/- 3 kg body weight) at 0 (n = 6), 7 (n = 6), 14 (n = 5), or 28 days (n = 4) after removal from grazing pasture (3.0 ha; endpoint ergovaline + ergovalinine = 1.35 mg/kg DM) for 126 days. In Experiment 2, lateral saphenous veins were biopsied from 24 Angus-cross steers (361 +/- 4 kg body weight) at 0, 21, 42, and 63 days (n = 6 per time point) following removal from grazing tall fescue pastures (3.0 ha; first 88 days endpoint ergovaline + ergovalinine = 0.15 mg/kg DM; last 18 days endpoint ergovaline + ergovalinine = 0.57 mg/kg DM) for 106 total days. Six steers (370 +/ 18 kg body weight) off of bermudagrass pasture for the same time interval were also biopsied on Day 0 and Day 63 (n = 3 per time point). Additionally, in Experiment 2, cross-sectional ultrasound scans of caudal artery at the fourth coccygeal vertebra were taken on Days 0, 8, 15, 21, 29, 36, 42, and 45 to determine mean artery luminal area to evaluate vasoconstriction. In both experiments, steers were removed from pasture and housed in a dry lot and fed a corn silage diet for the duration of biopsies and ultrasound scans. Biopsied vessels used to evaluate vasoactivity were cleaned, incubated in a multimyograph, and exposed to increasing concentrations of 4-Bromo-3,6-dimethoxybenzocyclobuten 1-yl) methylamine hydrobromide (TCB2; 5HT2A agonist), guanfacine (GF; alpha2A adrenergic agonist), and (R)-(+)-m-nitrobiphenyline oxalate (NBP; alpha2C adrenergic agonist) in both experiments and ergovaline (ERV) and ergotamine (ERT) in Experiments 1 and 2, respectively. In Experiment 1, days off pasture * agonist concentration was not significant (p > 0.1) for all four compounds tested. In Experiment 2, GF, NBP, TCB2 and ERT were significant for days off pasture * agonist concentration interaction (p < 0.02) and vasoactivity increased over time. Vasoactivity to agonists was reduced (p < 0.05) when steers were initially removed from E+ tall fescue pasture compared to bermudagrass, but did not differ by Day 63 for any variable. Luminal areas of caudal arteries in steers grazed on E+ tall fescue relaxed and were similar to steers that had grazed bermudagrass for 36 days on non-toxic diet (p = 0.15). These data demonstrate changes in peripheral vasoactivity and recovery from vasoconstriction occur beyond five weeks off toxic pasture and 5HT2A receptors appear to be more dramatically affected in the lateral saphenous vein by grazing E+ tall fescue pasture than adrenergic receptors. PMID- 27669300 TI - Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast. AB - Citrinin (CIT) and ochratoxin A (OTA) are important mycotoxins, which frequently co-contaminate foodstuff. In order to assess the toxicologic threat posed by the two mycotoxins separately or in combination, their biological effects were studied here using genomic transcription profiling and specific live cell gene expression reporters in yeast cells. Both CIT and OTA cause highly transient transcriptional activation of different stress genes, which is greatly enhanced by the disruption of the multidrug exporter Pdr5. Therefore, we performed genome wide transcription profiling experiments with the pdr5 mutant in response to acute CIT, OTA, or combined CIT/OTA exposure. We found that CIT and OTA activate divergent and largely nonoverlapping gene sets in yeast. CIT mainly caused the rapid induction of antioxidant and drug extrusion-related gene functions, while OTA mainly deregulated developmental genes related with yeast sporulation and sexual reproduction, having only a minor effect on the antioxidant response. The simultaneous exposure to CIT and OTA gave rise to a genomic response, which combined the specific features of the separated mycotoxin treatments. The application of stress-specific mutants and reporter gene fusions further confirmed that both mycotoxins have divergent biological effects in cells. Our results indicate that CIT exposure causes a strong oxidative stress, which triggers a massive transcriptional antioxidant and drug extrusion response, while OTA mainly deregulates developmental genes and only marginally induces the antioxidant defense. PMID- 27669301 TI - Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer. AB - Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotoxins for the treatment of glypican-3 (GPC3) expressing HCC. GPC3 is a cell surface heparan sulfate proteoglycan that is overexpressed in HCC, but is absent from normal adult human tissues. Treatment of HCC with anti-GPC3 immunotoxins represents a new therapeutic option. Using phage display and hybridoma technologies, three high affinity antibodies (HN3, HS20 and YP7) have been generated against GPC3. Two of these antibodies (HN3 and HS20) have demonstrated the ability to inhibit Wnt/Yap signaling, leading to a reduction in liver cancer cell proliferation. By combining the HN3 antibody capable of inhibiting Wnt/Yap signaling with the protein synthesis inhibitory domain of the Pseudomonas exotoxin, a recombinant immunotoxin that exhibits a dual inhibitory mechanism was generated. This immunotoxin was found to be highly effective in the treatment of human HCCs in mouse xenograft models. Engineering of the toxin fragment to reduce the level of immunogenicity is currently being explored. The development of immunotoxins provides opportunities for novel liver cancer therapies. PMID- 27669302 TI - The Mechanism of Diarrhetic Shellfish Poisoning Toxin Production in Prorocentrum spp.: Physiological and Molecular Perspectives. AB - Diarrhetic shellfish poisoning (DSP) is a gastrointestinal disorder caused by the consumption of seafood contaminated with okadaic acid (OA) and dinophysistoxins (DTXs). OA and DTXs are potent inhibitors of protein phosphatases 2A, 1B, and 2B, which may promote cancer in the human digestive system. Their expression in dinoflagellates is strongly affected by nutritional and environmental factors. Studies have indicated that the level of these biotoxins is inversely associated with the growth of dinoflagellates at low concentrations of nitrogen or phosphorus, or at extreme temperature. However, the presence of leucine or glycerophosphate enhances both growth and cellular toxin level. Moreover, the presence of ammonia and incubation in continuous darkness do not favor the toxin production. Currently, studies on the mechanism of this biotoxin production are scant. Full genome sequencing of dinoflagellates is challenging because of the massive genomic size; however, current advanced molecular and omics technologies may provide valuable insight into the biotoxin production mechanism and novel research perspectives on microalgae. This review presents a comprehensive analysis on the effects of various nutritional and physical factors on the OA and DTX production in the DSP toxin-producing Prorocentrum spp. Moreover, the applications of the current molecular technologies in the study on the mechanism of DSP toxin production are discussed. PMID- 27669303 TI - Development of an Innovative in Vitro Potency Assay for Anti-Botulinum Antitoxins. AB - Botulinum neurotoxins are bacterial proteins that cause botulism, a life threatening disease. Therapy relies mostly on post-intoxication antibody treatment. The only accepted method to measure the potency of, and to approve, antitoxin preparations is the mouse lethality neutralization bioassay. However, this assay is time-consuming, labor-intensive, costly, and raises ethical issues related to the large numbers of laboratory animals needed. Until now, all efforts to develop an alternative in vitro assay have not provided a valid replacement to the mouse potency assay. In the present study, we report the development of an innovative in vitro assay for determining botulinum antitoxin potency, using botulinum type B as a model. The concept of the assay is to mimic two fundamental steps in botulinum intoxication: receptor binding and catalytic activity. By simulating these steps in vitro we were able to accurately determine the potency of antitoxin preparations. The reproducibility of the assay was high with a CV < 13%. Most importantly, the antitoxin potency measured by the in vitro assay highly correlated with that measured by the standard in vivo mouse assay (r = 0.9842, p < 0.0001). Thus, this new in vitro assay has the potential to be considered, after validation, as a replacement to the mouse assay for quantitating neutralizing antibody concentrations in pharmaceutical botulinum antitoxin preparations. Future adoption of this in vitro assay would minimize the use of laboratory animals, speed up the time, and reduce the cost of botulinum antitoxin approval. PMID- 27669305 TI - Protective Effects of Sporoderm-Broken Spores of Ganderma lucidum on Growth Performance, Antioxidant Capacity and Immune Function of Broiler Chickens Exposed to Low Level of Aflatoxin B1. AB - This study was conducted to investigate the toxic effects of aflatoxin B1 (AFB1) and evaluate the effects of sporoderm-broken spores of Ganoderma lucidum (SSGL) in relieving aflatoxicosis in broilers. A total of 300 one-day-old male Arbor Acre broiler chickens were randomly divided into four dietary treatments; the treatment diets were: Control (a basal diet containing normal peanut meal); AFB1 (the basal diet containing AFB1-contaminated peanut meal); SSGL (basal diet with 200 mg/kg of SSGL); AFB1+SSGL (supplementation of 200 mg/kg of SSGL in AFB1 diet). The contents of AFB1 in AFB1 and AFB1+SSGL diets were 25.0 MUg/kg in the starter period and 22.5 MUg/kg in the finisher period. The results showed that diet contaminated with a low level of AFB1 significantly decreased (p < 0.05) the average daily feed intake and average daily gain during the entire experiment and reduced (p < 0.05) serum contents of total protein IgA and IgG. Furthermore, a dietary low level of AFB1 not only increased (p < 0.05) levels of hydrogen peroxide and lipid peroxidation, but also decreased (p < 0.05) total antioxidant capability, catalase, glutathione peroxidase, and hydroxyl radical scavenger activity in the liver and spleen of broilers. Moreover, the addition of SSGL to AFB1-contaminated diet counteracted these negative effects, indicating that SSGL has a protective effect against aflatoxicosis. PMID- 27669307 TI - Photodynamic Therapy in Gynecologic Malignancies: A Review of the Roswell Park Cancer Institute Experience. AB - Photodynamic therapy (PDT) is a treatment modality used in the management of solid tumor malignancies that employs the use of a photosensitizing agent, a light source and oxygen in order to illicit a direct cytotoxic effect. Its use in gynecologic malignancies is somewhat novel and has been used for palliative and curative intent. At the Roswell Park Cancer Institute, the use of PDT in the management of gynecologic cancers began in the mid 1980s and since that time 35 patients have received PDT as a treatment for recurrent or metastatic cutaneous and vulvar, vaginal, anal, and cervical recurrences. In our experience, 85% patients with metastatic cutaneous lesions had a complete response. Twenty-seven percent of patients with metastatic vaginal, cervical or anal recurrences had a complete response to therapy with a median response time of 28 months. Side effects from the treatment included moderate to severe burning sensation, pain and edema at the treatment site requiring narcotic pain medication for symptom management in patients who underwent treatment to cutaneous lesions as well as lower genital tract recurrences. PDT should be considered an option in patients who are too frail to undergo the standard of care or decline the standard of care in lieu of a less invasive treatment modality. PMID- 27669304 TI - Aerobic De-Epoxydation of Trichothecene Mycotoxins by a Soil Bacterial Consortium Isolated Using In Situ Soil Enrichment. AB - Globally, the trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) are among the most widely distributed mycotoxins that contaminate small grain cereals. In this study, a bacterial consortium, PGC-3, with de-epoxydation activity was isolated from soil by an in situ soil enrichment method. Screening of 14 soil samples that were sprayed with DON revealed that 4 samples were able to biotransform DON into de-epoxydized DON (dE-DON). Among these, the PGC-3 consortium showed the highest and most stable activity to biotransform DON into dE-DON and NIV into dE-NIV. PGC-3 exhibited de-epoxydation activity at a wide range of pH (5-10) and temperatures (20-37 degrees C) values under aerobic conditions. Sequential subculturing with a continued exposure to DON substantially reduced the microbial population diversity of this consortium. Analyses of the 16S rDNA sequences indicated that PGC-3 comprised 10 bacterial genera. Among these, one species, Desulfitobacterium, showed a steady increase in relative abundance, from 0.03% to 1.55% (a 52-fold increase), as higher concentrations of DON were used in the subculture media, from 0 to 500 MUg/mL. This study establishes the foundation to further develop bioactive agents that can detoxify trichothecene mycotoxins in cereals and enables for the characterization of detoxifying genes and their regulation. PMID- 27669306 TI - Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma. AB - The immune system plays a key role in preventing tumor formation by recognizing and destroying malignant cells. For over a century, researchers have attempted to harness the immune response as a cancer treatment, although this approach has only recently achieved clinical success. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is associated with cigarette smoking, alcohol consumption, betel nut use, and human papillomavirus infection. Unfortunately, worldwide mortality from HNSCC remains high, partially due to limits on therapy secondary to the significant morbidity associated with current treatments. Therefore, immunotherapeutic approaches to HNSCC treatment are attractive for their potential to reduce morbidity while improving survival. However, the application of immunotherapies to this disease has been challenging because HNSCC is profoundly immunosuppressive, resulting in decreased absolute lymphocyte counts, impaired natural killer cell function, reduced antigen presenting cell function, and a tumor-permissive cytokine profile. Despite these challenges, numerous clinical trials testing the safety and efficacy of immunotherapeutic approaches to HNSCC treatment are currently underway, many of which have produced promising results. This review will summarize immunotherapeutic approaches to HNSCC that are currently undergoing clinical trials. PMID- 27669308 TI - Making Sense of the Tangle: Insights into Chromatin Folding and Gene Regulation. AB - Proximity ligation assays such as circularized chromosome conformation capture and high-throughput chromosome capture assays have shed light on the structural organization of the interphase genome. Functional topologically associating domains (TADs) that constitute the building blocks of genomic organization are disrupted and reconstructed during the cell cycle. Epigenetic memory, as well as the sequence of chromosomes, regulate TAD reconstitution. Sub-TAD domains that are invariant across cell types have been identified, and contacts between these domains, rather than looping, are speculated to drive chromatin folding. Replication domains are established simultaneously with TADs during the cell cycle and the two correlate well in terms of characteristic features, such as lamin association and histone modifications. CCCTC-binding factor (CTCF) and cohesin cooperate across different cell types to regulate genes and genome organization. CTCF elements that demarcate TAD boundaries are commonly disrupted in cancer and promote oncogene activation. Chromatin looping facilitates interactions between distant promoters and enhancers, and the resulting enhanceosome complex promotes gene expression. Deciphering the chromatin tangle requires comprehensive integrative analyses of DNA- and protein-dependent factors that regulate genomic organization. PMID- 27669309 TI - Transition and Transversion Mutations Are Biased towards GC in Transposons of Chilo suppressalis (Lepidoptera: Pyralidae). AB - Transposons are often regulated by their hosts, and as a result, there are transposons with several mutations within their host organisms. To gain insight into the patterns of the variations, nucleotide substitutions and indels of transposons were analysed in Chilo suppressalis Walker. The CsuPLE1.1 is a member of the piggyBac-like element (PLE) family, which belongs to the DNA transposons, and the Csu-Ty3 is a member of the Ty3/gypsy family, which belongs to the RNA transposons. Copies of CsuPLE1.1 and Csu-Ty3 were cloned separately from different C. suppressalis individuals, and then multiple sequence alignments were performed. There were numerous single-base substitutions in CsuPLE1.1 and Csu Ty3, but only a few insertion and deletion mutations. Similarly, in both transposons, the occurring frequencies of transitions were significantly higher than transversions (p <= 0.01). In the single-base substitutions, the most frequently occurring base changes were A->G and T->C in both types of transposons. Additionally, single-base substitution frequencies occurring at positions 1, 2 or 3 (pos1, pos2 or pos3) of a given codon in the element transposase were not significantly different. Both in CsuPLE1.1 and Csu-Ty3, the patterns of nucleotide substitution had the same characteristics and nucleotide mutations were biased toward GC. This research provides a perspective on the understanding of transposon mutation patterns. PMID- 27669310 TI - Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis. AB - Xeroderma pigmentosum group C (XPC) is a key component of the nucleotide excision repair (NER) pathway. Dysfunctional XPC protein may impair NER-mediated DNA repair capacity and further lead to genomic instability and carcinogenesis. Two common nonsynonymous polymorphisms in the XPC gene, Lys939Gln (rs2228001 A > C) and Ala499Val (rs2228000 C > T), have been investigated in various types of cancer. We genotyped these two polymorphisms in 1141 cases with histologically confirmed colorectal cancer (CRC) and 1173 healthy controls to explore their causative association with CRC susceptibility. Overall, no association was observed between these two variants and the risk of CRC. Our meta-analysis also confirmed a lack of overall association. Stratified analyses were performed by age, gender, smoking status, pack-year, drinking status, tumor sites, and Duke's stages. We found that XPC Lys939Gln polymorphism was significantly associated with an increased CRC risk in subjects at 57 years of age or younger (adjusted odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.004-1.86, p = 0.047) and non-drinkers (adjusted OR = 1.53, 95% CI = 1.10-2.12, p = 0.011). Our results indicated that XPC Lys939Gln may be a low-penetrance CRC susceptibility polymorphism. Our findings warrant further validation. PMID- 27669311 TI - Presence of a Prophage Determines Temperature-Dependent Capsule Production in Streptococcus pyogenes. AB - A hyaluronic acid capsule is a major virulence factor in the pathogenesis of Streptococcus pyogenes. It acts as an anti-phagocytic agent and adhesin to keratinocytes. The expression of the capsule is primarily regulated at the transcriptional level by the two-component regulatory system CovRS, in which CovR acts as a transcriptional repressor. The covRS genes are frequently mutated in many invasive strains, and a subset of the invasive CovRS mutants does not produce a detectable level of the capsule at 37 degrees C, but produces a significant amount of the capsule at sub-body temperatures. Here, we report that a prophage has a crucial role in this capsule thermoregulation. Passaging CovR null strains showing capsule thermoregulation using a lab medium produced spontaneous mutants producing a significant amount of the capsule regardless of incubation temperature and this phenotypic change was caused by curing of a particular prophage. The lab strain HSC5 contains three prophages on the chromosome, and only PhiHSC5.3 was cured in all spontaneous mutants. This result indicates that the prophage PhiHSC5.3 plays a crucial role in capsule thermoregulation, most likely by repressing capsule production at 37 degrees C. PMID- 27669312 TI - Comparison of Model Predictions and Laboratory Observations of Transgene Frequencies in Continuously-Breeding Mosquito Populations. AB - The persistence of transgenes in the environment is a consideration in risk assessments of transgenic organisms. Combining mathematical models that predict the frequency of transgenes and experimental demonstrations can validate the model predictions, or can detect significant biological deviations that were neither apparent nor included as model parameters. In order to assess the correlation between predictions and observations, models were constructed to estimate the frequency of a transgene causing male sexual sterility in simulated populations of a malaria mosquito Anopheles gambiae that were seeded with transgenic females at various proportions. Concurrently, overlapping-generation laboratory populations similar to those being modeled were initialized with various starting transgene proportions, and the subsequent proportions of transgenic individuals in populations were determined weekly until the transgene disappeared. The specific transgene being tested contained a homing endonuclease gene expressed in testes, I-PpoI, that cleaves the ribosomal DNA and results in complete male sexual sterility with no effect on female fertility. The transgene was observed to disappear more rapidly than the model predicted in all cases. The period before ovipositions that contained no transgenic progeny ranged from as little as three weeks after cage initiation to as long as 11 weeks. PMID- 27669313 TI - Moving beyond the "Five Freedoms" by Updating the "Five Provisions" and Introducing Aligned "Animal Welfare Aims". AB - Although the Five Freedoms paradigm has been very influential in shaping animal welfare thinking for the last two decades, it has two key disadvantages. First, the focus on "freedom" from a range of negative experiences and states has been misunderstood in a number of quarters to mean that complete freedom from these experiences and states is possible, when in fact the best that can be achieved is for them to be minimised. Second, the major focus of the Freedoms on negative experiences and states is now seen to be a disadvantage in view of current understanding that animal welfare management should also include the promotion of positive experiences and states. The challenge therefore was to formulate a paradigm that overcame these two main problems and yet was straightforward enough to be accessible to non-specialists, including members of the lay public who are interested in animal welfare. This was achieved by highlighting the Five Provisions, originally aligned with the Five Freedoms, but now updated to direct welfare management towards activities that both minimise negative experiences or states and promote positive experiences or states as specified by particular Animal Welfare Aims assigned to each Provision. Aspects of the four welfare principles from the European Welfare Quality assessment system (WQ ((r)) ) and elements of all domains of the Five Domains Model for animal welfare assessment have been incorporated into the new Five Provisions/Welfare Aims paradigm. Thus, the paradigm is easily understood and provides clear guidance on beneficial objectives for animal welfare management. It is anticipated that the paradigm will have application to many species found in a wide range of circumstances. PMID- 27669314 TI - The Effect of Computerized Testing on Sun Bear Behavior and Enrichment Preferences. AB - The field of comparative cognition investigates species' differences and similarities in cognitive abilities, and sheds light on the evolutionary origins of such capacities. Cognitive testing has been carried out in a variety of species; however, there are some taxa that are underrepresented in this field. The current work follows on a recent increase in cognitive research in the order Carnivora with a specific focus on sun bears. Sun bears are the smallest existing bear species and live in tropical regions of Southeast Asia. They have an omnivorous diet and use their tongues to forage for insects and sap. Little is known about sun bear cognition, although much like other bear species, anecdotes suggest a high level of intelligence. The current work explored training sun bears to use a touchscreen computer. This effort allows for insight into cognitive abilities as well as providing a complex source of enrichment for the bears. The bears use their tongues to respond to a touchscreen computer, and the effects on stereotypic behaviors on exhibit and preference for this over other forms of enrichment were examined. Overall, bears performed well on the task and showed a preference for the computer. PMID- 27669316 TI - OSAnalyzer: A Bioinformatics Tool for the Analysis of Gene Polymorphisms Enriched with Clinical Outcomes. AB - BACKGROUND: The identification of biomarkers for the estimation of cancer patients' survival is a crucial problem in modern oncology. Recently, the Affymetrix DMET (Drug Metabolizing Enzymes and Transporters) microarray platform has offered the possibility to determine the ADME (absorption, distribution, metabolism, and excretion) gene variants of a patient and to correlate them with drug-dependent adverse events. Therefore, the analysis of survival distribution of patients starting from their profile obtained using DMET data may reveal important information to clinicians about possible correlations among drug response, survival rate, and gene variants. METHODS: In order to provide support to this analysis we developed OSAnalyzer, a software tool able to compute the overall survival (OS) and progression-free survival (PFS) of cancer patients and evaluate their association with ADME gene variants. RESULTS: The tool is able to perform an automatic analysis of DMET data enriched with survival events. Moreover, results are ranked according to statistical significance obtained by comparing the area under the curves that is computed by using the log-rank test, allowing a quick and easy analysis and visualization of high-throughput data. CONCLUSIONS: Finally, we present a case study to highlight the usefulness of OSAnalyzer when analyzing a large cohort of patients. PMID- 27669315 TI - Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson's Disease. AB - Parkinson's disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within the context of aging as it applies to the development of PD, and the potential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology that modulates neurodegeneration that occurs in Parkinson's disease. PMID- 27669317 TI - Tart Cherry Extracts Reduce Inflammatory and Oxidative Stress Signaling in Microglial Cells. AB - Tart cherries contain an array of polyphenols that can decrease inflammation and oxidative stress (OS), which contribute to cognitive declines seen in aging populations. Previous studies have shown that polyphenols from dark-colored fruits can reduce stress-mediated signaling in BV-2 mouse microglial cells, leading to decreases in nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression. Thus, the present study sought to determine if tart cherries-which improved cognitive behavior in aged rats-would be efficacious in reducing inflammatory and OS signaling in HAPI rat microglial cells. Cells were pretreated with different concentrations (0-1.0 mg/mL) of Montmorency tart cherry powder for 1-4 h, then treated with 0 or 100 ng/mL lipopolysaccharide (LPS) overnight. LPS application increased extracellular levels of NO and tumor necrosis factor-alpha (TNF-alpha), and intracellular levels of iNOS and cyclooxygenase-2 (COX-2). Pretreatment with tart cherry decreased levels of NO, TNF-alpha, and COX-2 in a dose- and time-dependent manner versus those without pretreatment; the optimal combination was between 0.125 and 0.25 mg/mL tart cherry for 2 h. Higher concentrations of tart cherry powder and longer exposure times negatively affected cell viability. Therefore, tart cherries (like other dark-colored fruits), may be effective in reducing inflammatory and OS-mediated signals. PMID- 27669318 TI - Immunotherapy for Gastroesophageal Cancer. AB - Survival for patients with advanced oesophageal and stomach cancer is poor; together these cancers are responsible for more than a million deaths per year globally. As chemotherapy and targeted therapies such as trastuzumab and ramucirumab result in modest improvements in survival but not long-term cure for such patients, development of alternative treatment approaches is warranted. Novel immunotherapy drugs such as checkpoint inhibitors have been paradigm changing in melanoma, non-small cell lung cancer and urothelial cancers. In this review, we assess the early evidence for efficacy of immunotherapy in patients with gastroesophageal cancer in addition to considering biomarkers associated with response to these treatments. Early results of Anti- Programmed Cell Death Protein-1 (anti-PD-1), anti-PD-L1 and anti-Cytotoxic T-lymphocyte assosciated protein-4 (anti-CTLA4) trials are examined, and we conclude with a discussion on the future direction for immunotherapy for gastroesophageal cancer patients. PMID- 27669319 TI - Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea. AB - Platypnea-orthodexia syndrome (POS) is often a challenging diagnostic problem. It is characterized by dyspnea that is accentuated by standing or sitting positions due to a marked fall in blood oxygen saturation, and instead is improved by assuming the lying position. In the present brief review, the authors address the pathophysiology of POS, and outline its clinical symptoms as well as the main modalities of diagnostic evaluation and possible therapeutic options. Moreover, some problems concerning much-debated issues and persistent uncertainties about the pathophysiology of POS are presented along with the description of the diagnostic and therapeutic resources currently available for this syndrome. PMID- 27669320 TI - Rapid, Portable, Multiplexed Detection of Bacterial Pathogens Directly from Clinical Sample Matrices. AB - Enteric and diarrheal diseases are a major cause of childhood illness and death in countries with developing economies. Each year, more than half of a million children under the age of five die from these diseases. We have developed a portable, microfluidic platform capable of simultaneous, multiplexed detection of several of the bacterial pathogens that cause these diseases. This platform can perform fast, sensitive immunoassays directly from relevant, complex clinical matrices such as stool without extensive sample cleanup or preparation. Using only 1 uL of sample per assay, we demonstrate simultaneous multiplexed detection of four bacterial pathogens implicated in diarrheal and enteric diseases in less than 20 min. PMID- 27669321 TI - The Novel Aminomethylcycline Omadacycline Has High Specificity for the Primary Tetracycline-Binding Site on the Bacterial Ribosome. AB - Omadacycline is an aminomethylcycline antibiotic with potent activity against many Gram-positive and Gram-negative pathogens, including strains carrying the major efflux and ribosome protection resistance determinants. This makes it a promising candidate for therapy of severe infectious diseases. Omadacycline inhibits bacterial protein biosynthesis and competes with tetracycline for binding to the ribosome. Its interactions with the 70S ribosome were, therefore, analyzed in great detail and compared with tigecycline and tetracycline. All three antibiotics are inhibited by mutations in the 16S rRNA that mediate resistance to tetracycline in Brachyspira hyodysenteriae, Helicobacter pylori, Mycoplasma hominis, and Propionibacterium acnes. Chemical probing with dimethyl sulfate and Fenton cleavage with iron(II)-complexes of the tetracycline derivatives revealed that each antibiotic interacts in an idiosyncratic manner with the ribosome. X-ray crystallography had previously revealed one primary binding site for tetracycline on the ribosome and up to five secondary sites. All tetracyclines analyzed here interact with the primary site and tetracycline also with two secondary sites. In addition, each derivative displays a unique set of non-specific interactions with the 16S rRNA. PMID- 27669322 TI - The Peptidoglycan Pattern of Staphylococcus carnosus TM300-Detailed Analysis and Variations Due to Genetic and Metabolic Influences. AB - The Gram-positive bacterium Staphylococcus carnosus (S. carnosus) TM300 is an apathogenic staphylococcal species commonly used in meat starter cultures. As with all Gram-positive bacteria, its cytoplasmic membrane is surrounded by a thick peptidoglycan (PGN) or murein sacculus consisting of several layers of glycan strands cross-linked by peptides. In contrast to pathogenic staphylococci, mainly Staphylococcus aureus (S. aureus), the chemical composition of S. carnosus PGN is not well studied so far. UPLC/MS analysis of enzymatically digested S. carnosus TM300 PGN revealed substantial differences in its composition compared to the known pattern of S. aureus. While in S. aureus the uncross-linked stem peptide consists of a pentapeptide, in S. carnosus, this part of the PGN is shortened to tripeptides. Furthermore, we found the PGN composition to vary when cells were incubated under certain conditions. The collective overproduction of HlyD, FtsE and FtsX-a putative protein complex interacting with penicillin binding protein 2 (PBP2)-caused the reappearance of classical penta stem peptides. In addition, under high sugar conditions, tetra stem peptides occur due to overflow metabolism. This indicates that S. carnosus TM300 cells adapt to various conditions by modification of their PGN. PMID- 27669324 TI - Symptom Management in Patients with Stage 5 CKD Opting for Conservative Management. AB - Chronic kidney disease (CKD) stages 3-5 now affects 8.5% of adults in the United Kingdom; with 4% of patients expected to reach stage 5 CKD. Increasing numbers of older patients are contributing to the growth of demand of kidney services. With the exception of transplantation, dialysis has been the main form of renal replacement therapy (RRT) for advanced CKD. This elderly population is usually too frail and has many other co-existing medical complaints or co morbidities to undergo transplantation. Dialysis is an invasive treatment, and some frail elderly patients can experience many dialysis related symptoms. An alternative option for these patients is to choose conservative management (CM) of their stage 5 CKD. These patients often have complex supportive and palliative care needs. The frequency, severity and distress caused by symptoms related to stage 5 CKD are often under recognized and under treated. There is a need for early identification and management of symptoms as they present in patients with stage 5 CKD being managed conservatively. Symptom assessment should be focused on anticipating, identifying and alleviating any symptoms. This needs to be incorporated into the regular practice of those managing CM patients. PMID- 27669323 TI - Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells. AB - Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect-an increase in glycolytic activity at the expense of oxidative phosphorylation-and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions. PMID- 27669325 TI - Malnutrition Affects the Urban-Poor Disproportionately: A Study of Nigerian Urban Children of Different Socio-Economic Statuses. AB - Income inequality within the same place of residence may impact the nutritional status of children. This study therefore investigated the impact of income inequality on the nutritional status of children living in the same place of residence, using anthropometric tools. Children in four schools (Schools 1-4) within the vicinity of a housing estate in Umuahia, Nigeria, that charge fees making them 'very affordable', 'affordable', 'expensive' and 'very expensive', respectively, were recruited for the study. Thinness, overweight and obesity were defined using the Cole et al. reference standards. Thinness was present in 10.4% (13.0% of boys, 7.6% of girls); 20.4% (15.6% of boys, 27.3% of girls; and 0.7% (1.4% of boys, 0.0% of girls) of children in Schools 1-3, respectively; but absent in school 4. Only 3.7% (1.4% of boys, 6.1% of girls) and 5.6% (6.3% of boys, 4.5% of girls) of children in Schools 1 and 2, respectively, were overweight/obese. Conversely, 25.8% (18.9% of boys, 32.5% of girls) and 41.6% (38.8% of boys, 45.3% of girls) of children in Schools 3 and 4, respectively, were overweight/obese. The urban-poor (School 2) are clearly affected by malnutrition disproportionately. PMID- 27669327 TI - Mechanically stable nanostructures with desirable characteristic field enhancement factors: a response from scale invariance in electrostatics. AB - This work presents an accurate numerical study of the electrostatics of a system formed by individual nanostructures mounted on support substrate tips, which provides a theoretical prototype for applications in field electron emission or for the construction of tips in probe microscopy that requires high resolution. The aim is to describe the conditions to produce structures mechanically robust with desirable field enhancement factor (FEF). We modeled a substrate tip with a height h 1, radius r 1 and characteristic FEF [Formula: see text], and a top nanostructure with a height h 2, radius [Formula: see text] and FEF [Formula: see text], for both hemispheres on post-like structures. The nanostructure mounted on the support substrate tip then has a characteristic FEF, [Formula: see text]. Defining the relative difference [Formula: see text], where [Formula: see text] corresponds to the reference FEF for a hemisphere of the post structure with a radius [Formula: see text] and height [Formula: see text], our results show, from a numerical solution of Laplace's equation using a finite element scheme, a scaling [Formula: see text], where [Formula: see text] and [Formula: see text]. Given a characteristic variable u c, for [Formula: see text], we found a power law [Formula: see text], with [Formula: see text]. For [Formula: see text], [Formula: see text], which led to conditions where [Formula: see text]. As a consequence of scale invariance, it is possible to derive a simple expression for [Formula: see text] and to predict the conditions needed to produce related systems with a desirable FEF that are robust owing to the presence of the substrate tip. Finally, we discuss the validity of Schottky's conjecture (SC) for these systems, showing that, while to obey SC is indicative of scale invariance, the opposite is not necessarily true. This result suggests that a careful analysis must be performed before attributing SC as an origin of giant FEF in experiments. PMID- 27669326 TI - Enzyme-catalyzed expressed protein ligation. AB - Expressed protein ligation is a valuable method for protein semisynthesis that involves the reaction of recombinant protein C-terminal thioesters with N terminal cysteine (N-Cys)-containing peptides, but the requirement of a Cys residue at the ligation junction can limit the utility of this method. Here we employ subtiligase variants to efficiently ligate Cys-free peptides to protein thioesters. Using this method, we have more accurately determined the effect of C terminal phosphorylation on the tumor suppressor protein PTEN. PMID- 27669328 TI - Na-Rich Na3+xV2-xNix(PO4)3/C for Sodium Ion Batteries: Controlling the Doping Site and Improving the Electrochemical Performances. AB - In order to get an element substituted into Na3V2(PO4)3/C in an appointed V site, the simple sol-gel method is used to design and prepare a series of Na-rich Na3+xV2-xNix(PO4)3/C (x = 0-0.07) compounds. To get a charge balance, the ratio of Na, V, and Ni would be changed if Ni goes into a different site. Hence, ICP is applied to probe the real stoichiometry of the as-prepared Na3+xV2-xNix(PO4)3/C (x = 0-0.07). According to the Na/V ratio from the ICP result, it indicates that Ni2+ goes to a V site, and more Na+ will be introduced into the crystal to keep the charge balance. In addition, the crystal structure changes are explored by XRD and Rietveld refinement, it is indicated from the results that Ni2+ doping does not destroy the lattice structure of Na3V2(PO4)3. When applied as Na-storage material, the electrochemical property of all Ni2+ doped Na3+xV2-xNix(PO4)3/C composites have been significantly improved, especially for the Na3.03V1.97Ni0.03(PO4)3/C sample. For example, 107.1 mAh g-1 can be obtained at the first cycle; after 100 cycles, the capacity retention is as high as 95.5%. Moreover, when charging/discharging at a higher rate of 5 C, the capacity still remains 88.9 mAh g-1, displaying good rate performance. The good electrochemical performance is ascribed to the optimized morphology, stable crystal structure, and improved ionic conductivity. PMID- 27669329 TI - Ciliary Body/Iris Appositioning Producing Mechanical Pupillary Defects in Carotid Cavernous Sinus Fistula: An Overlooked Pathophysiologic Mechanism. AB - BACKGROUND: Variable pupillary responses have been described with carotid cavernous sinus fistulas. These often are associated with a decrease in visual acuity and attributed to retinal ischemia. We propose a novel pathophysiologic mechanism for changes in pupillary reactivity involving anatomic changes secondary to choroidal effusion. METHODS: To demonstrate proof-of-concept, we investigated 2 consecutive patients with carotid-cavernous sinus fistulas and pupillary disturbances using repeated refractions and anterior segment ultrasound biomicroscopy. RESULTS: Ultrasound biomicroscopy demonstrated choroidal thickening and ciliary body effusion with forward rotation of the lens-iris diaphragm altering refraction and mechanically limiting iris movements. CONCLUSIONS: Where there are acute elevations in orbital venous pressure causing ciliary body effusion, changes in visual acuity and pupillary abnormalities can be produced by mechanical effects. PMID- 27669330 TI - Enhanced Stability of Laminated Graphene Oxide Membranes for Nanofiltration via Interstitial Amide Bonding. AB - Laminated graphene oxide (GO) has promising use as a membrane because of its high permeance, chemical and mechanical stability, as well as the molecular sieving effect of its interlayers. However, the hydrophilic surface of GO, which is highly decorated with oxygen groups, easily induces delamination of stacked GO films in aqueous media, thereby limiting the practical application. To stabilize GO films in aqueous media, we functionalized a polymer support with branched polyethylene-imine (BPEI). BPEI adsorbed intercalated into the stacked GO sheets via diffusion during filtration. The GO/BPEI membrane obtained exhibits high stability during sonication (>1 h duration, 40 kHz frequency) in water within a broad pH range (2-12). In contrast, the GO film spontaneously delaminated upon sonication. Furthermore, BPEI treatment did not affect the filtration performance of the GO film, as evidenced by the high rejection rates (>90%) for the dye molecules methylene blue, rose bengal, and brilliant blue and by their permeation rates of ca. 124, 34.8, 12.2, and 5.1%, respectively, relative to those of a typical GO membrane. PMID- 27669331 TI - Rates of Neonatal Abstinence Syndrome Amid Efforts to Combat the Opioid Abuse Epidemic. PMID- 27669332 TI - Fostering Transparency in Outcomes, Quality, Safety, and Costs. PMID- 27669333 TI - A Call for a Patient-Centered Response to Legalized Assisted Dying. PMID- 27669334 TI - Spirometry filters can be used to detect exhaled respiratory viruses. AB - Respiratory viruses are very common in the community and contribute to the burden of illness for patients with chronic respiratory diseases, including acute exacerbations. Traditional sampling methods are invasive and problematic to repeat. Accordingly, we explored whether respiratory viruses could be isolated from disposable spirometry filters and whether detection of viruses in this context represented presence in the upper or lower respiratory tract. Discovery (n = 53) and validation (n = 49) cohorts were recruited from a hospital outpatient department during two different time periods. Spirometry mouthpiece filters were collected from all participants. Respiratory secretions were sampled from the upper and lower respiratory tract by nasal washing (NW), sputum, and bronchoalveolar lavage (BAL). All samples were examined using RT-PCR to identify a panel of respiratory viruses (rhinovirus, respiratory syncytial virus, influenza A, influenza B, parainfluenza virus 1, 2 & 3, and human metapneumovirus). Rhinovirus was quantified using qPCR. Paired filter-NW samples (n = 29), filter-sputum samples (n = 24), filter-BAL samples (n = 39) and filter-NW-BAL samples (n = 10) provided a range of comparisons. At least one virus was detected in any sample in 85% of participants in the discovery cohort versus 45% in the validation cohort. Overall, 72% of viruses identified in the paired comparator method matched those detected in spirometry filters. There was a high correlation between viruses identified in spirometry filters compared with viruses identified in both the upper and lower respiratory tract using traditional sampling methods. Our results suggest that examination of spirometry filters may be a novel and inexpensive sampling method for the presence of respiratory viruses in exhaled breath. PMID- 27669335 TI - Iron Deficiency Impairs Developing Hippocampal Neuron Gene Expression, Energy Metabolism, and Dendrite Complexity. AB - Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of the iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a degree of neuronal ID similar to that seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e. BdnfVI,Camk2a,Vamp1,Psd95,Cfl1, Pfn1,Pfn2, and Gda) and mitochondrial function (i.e. Ucp2,Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons were reduced. By 18DIV, partial recovery of the dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and the length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism, is responsible for the effects of fetal/neonatal ID and IDA on hippocampal neuron dendritic and synaptic maturation. Impairments in these neurodevelopmental processes likely underlie the negative impact of early life ID and IDA on hippocampus-mediated learning and memory. PMID- 27669337 TI - Toward a Deeper Understanding of Nausea, Vomiting, and Pregnancy Loss. PMID- 27669336 TI - Rebound Syndrome in Multiple Sclerosis After Fingolimod Cessation. PMID- 27669338 TI - ChemDataExtractor: A Toolkit for Automated Extraction of Chemical Information from the Scientific Literature. AB - The emergence of "big data" initiatives has led to the need for tools that can automatically extract valuable chemical information from large volumes of unstructured data, such as the scientific literature. Since chemical information can be present in figures, tables, and textual paragraphs, successful information extraction often depends on the ability to interpret all of these domains simultaneously. We present a complete toolkit for the automated extraction of chemical entities and their associated properties, measurements, and relationships from scientific documents that can be used to populate structured chemical databases. Our system provides an extensible, chemistry-aware, natural language processing pipeline for tokenization, part-of-speech tagging, named entity recognition, and phrase parsing. Within this scope, we report improved performance for chemical named entity recognition through the use of unsupervised word clustering based on a massive corpus of chemistry articles. For phrase parsing and information extraction, we present the novel use of multiple rule based grammars that are tailored for interpreting specific document domains such as textual paragraphs, captions, and tables. We also describe document-level processing to resolve data interdependencies and show that this is particularly necessary for the autogeneration of chemical databases since captions and tables commonly contain chemical identifiers and references that are defined elsewhere in the text. The performance of the toolkit to correctly extract various types of data was evaluated, affording an F-score of 93.4%, 86.8%, and 91.5% for extracting chemical identifiers, spectroscopic attributes, and chemical property attributes, respectively; set against the CHEMDNER chemical name extraction challenge, ChemDataExtractor yields a competitive F-score of 87.8%. All tools have been released under the MIT license and are available to download from http://www.chemdataextractor.org . PMID- 27669345 TI - Democratization of Health Care. PMID- 27669346 TI - Spin Crossover in the {Fe(pz)[Pt(CN)4]} Metal-Organic Framework upon Pyrazine Adsorption. AB - The spin-crossover behavior of the {Fe(pz)[Pt(CN)4]} metal-organic framework (MOF) upon pyrazine adsorption is investigated through hybrid Monte Carlo/molecular dynamics (MC/MD) simulations. In contrast to previous theoretical studies, which reported a transition temperature of ~140 K, the present MC/MD simulations predict that the high-spin state is the most stable state at all temperatures, in agreement with the experimental observations. The MC/MD simulations also indicate that the pyrazine molecules adsorbed in the MOF pores lie nearly parallel but staggered by 60 degrees relative to the pyrazine ligands of the framework. The analysis of the magnetization curve as a function of the temperature demonstrates that the staggered configuration assumed by the guest pyrazine molecules within the framework is responsible for the stabilization of the high-spin state. Both the guest pyrazine molecules and the pyrazine ligands of the framework are effectively locked into the minimum-energy configuration and do not display any rotational mobility. PMID- 27669347 TI - August consultation #2. PMID- 27669348 TI - Fifty-six-year-old woman unable to drive at night after routine cataract surgery: August consultation #1. PMID- 27669349 TI - August consultation #3. PMID- 27669350 TI - August consultation #5. PMID- 27669351 TI - August consultation #4. PMID- 27669352 TI - August consultation #7. PMID- 27669353 TI - August consultation #6. PMID- 27669354 TI - August consultation #8. PMID- 27669355 TI - "A qualitative meta-analysis examining clients' experiences of psychotherapy: A new agenda": Correction to Levitt, Pomerville, and Surace (2016). AB - Reports an error in "A qualitative meta-analysis examining clients' experiences of psychotherapy: A new agenda" by Heidi M. Levitt, Andrew Pomerville and Francisco I. Surace (Psychological Bulletin, 2016[Aug], Vol 142[8], 801-830). In the article, the 2nd sentence in the Broadening the Forms of Power When Considering Client-Therapist Differences section, "Indeed, most of the studies (55/66, 83.3%) in these categories focused either on the power differential within the therapeutic relationship (37) or culturally based power differences between therapists and clients (29)." should read: "Indeed, most of the studies (49/59, 83.1%) in these categories focused either on the power differential within the therapeutic relationship (38) or culturally based power differences between therapists and clients (31)." (The following abstract of the original article appeared in record 2016-21269-001.) This article argues that psychotherapy practitioners and researchers should be informed by the substantive body of qualitative evidence that has been gathered to represent clients' own experiences of therapy. The current meta-analysis examined qualitative research studies analyzing clients' experiences within adult individual psychotherapy that appeared in English-language journals. This omnibus review integrates research from across psychotherapy approaches and qualitative methods, focusing on the cross-cutting question of how clients experience therapy. It utilized an innovative method in which 67 studies were subjected to a grounded theory meta analysis in order to develop a hierarchy of data and then 42 additional studies were added into this hierarchy using a content meta-analytic method-summing to 109 studies in total. Findings highlight the critical psychotherapy experiences for clients, based upon robust findings across these research studies. Process focused principles for practice are generated that can enrich therapists' understanding of their clients in key clinical decision-making moments. Based upon these findings, an agenda is suggested in which research is directed toward heightening therapists' understanding of clients and recognizing them as agents of change within sessions, supporting the client as self-healer paradigm. This research aims to improve therapists' sensitivity to clients' experiences and thus can expand therapists' attunement and intentionality in shaping interventions in accordance with whichever theoretical orientation is in use. The article advocates for the full integration of the qualitative literature in psychotherapy research in which variables are conceptualized in reference to an understanding of clients' experiences in sessions. PMID- 27669356 TI - Absorption Spectroscopy of an Individual Fano Cluster. AB - Plasmonic clusters can exhibit Fano resonances with unique and tunable asymmetric line shapes, which arise due to the coupling of bright and dark plasmon modes within each multiparticle structure. These structures are capable of generating remarkably large local electromagnetic field enhancements and should give rise to high hot carrier yields relative to other plasmonic nanostructures. While the scattering properties of individual plasmonic Fano resonances have been characterized extensively both experimentally and theoretically, their absorption properties, critical for hot carrier generation, have not yet been measured. Here, we utilize single-particle absorption spectroscopy based on photothermal imaging to distinguish between the radiative and nonradiative properties of an individual Fano cluster. In observing the absorption spectrum of individual Fano clusters, we directly verify the theoretical prediction that while Fano interference may be prominent in scattering, it is completely absent in absorption. Our results provide microscopic insight into the nature of Fano interference in systems of coupled plasmonic nanoparticles and should pave the way for the optimization of hot carrier production using plasmonic Fano clusters. PMID- 27669357 TI - Surface Chemistry of Semiconducting Quantum Dots: Theoretical Perspectives. AB - Colloidal quantum dots (QDs) are near-ideal nanomaterials for energy conversion and lighting technologies. However, their photophysics exhibits supreme sensitivity to surface passivation and defects, of which control is problematic. The role of passivating ligands in photodynamics remains questionable and is a focus of ongoing research. The optically forbidden nature of surface-associated states makes direct measurements on them challenging. Therefore, computational modeling is imperative for insights into surface passivation and its impact on light-driven processes in QDs. This Account discusses challenges and recent progress in understanding surface effects on the photophysics of QDs addressed via quantum-chemical calculations. We overview different methods, including the effective mass approximation (EMA), time-dependent density functional theory (TDDFT), and multiconfiguration approaches, considering their strengths and weaknesses relevant to modeling of QDs with a complicated surface. We focus on CdSe, PbSe, and Si QDs, where calculations successfully explain experimental trends sensitive to surface defects, doping, and ligands. We show that the EMA accurately describes both linear and nonlinear optical properties of large-sized CdSe QDs (>2.5 nm), while TDDFT is required for smaller QDs where surface effects dominate. Both approaches confirm efficient two-photon absorption enabling applications of QDs as nonlinear optical materials. TDDFT also describes the effects of morphology on the optical response of QDs: the photophysics of stoichiometric, magic-sized XnYn (X = Cd, Pb; Y = S, Se) QDs is less sensitive to their passivation compared with nonstoichiometric Xn?mYm QDs. In the latter, surface-driven optically inactive midgap states can be eliminated by anionic ligands, explaining the better emission of metal-enriched QDs compared with nonmetal-enriched QDs. Ideal passivation of magic-sized QDs by amines and phosphine oxides leaves lower-energy transitions intact, while thiol derivatives add ligand-localized trap states to the band gap. Depending on its position, any loss of ligand from the QD's surface also introduces electron or hole traps, decreasing the QD's luminescence. TDDFT investigations of QD-ligand and QD-QD interactions provide an explanation of experimentally detected enhancement of blinking on-times in closely packed Si QDs and establish favorable conditions for hole transfer from the photoexcited CdSe QD to metal-organic dyes. While TDDFT well describes qualitative trends in optical response to stoichiometry and ligand modifications of QDs, it is unable to calculate highly correlated electronic states like biexcitons and magnetic-dopant-derived states. In these cases, multiconfiguration methods are applied to small nanoclusters and the results are extrapolated to larger-sized QDs, providing reasonable explanations of experimental observables. For light-driven dynamics, the electron-phonon couplings are important, and nonadiabatic dynamics (NAD) is applied. NAD based on first-principles calculations is a current grand challenge for the theory. However, it can be accomplished through sets of semiclassical approximations such as surface hopping (SH). We discuss validations of approximations used in photodynamics of ligated and doped QDs. Time-domain DFT-based SH-NAD reveals the ligand's role in ultrafast energy relaxation and the connection between the phonon bottleneck and the Zeno effect in CdSe QDs. The calculated results are helpful in controlling both dissipation and radiative processes in QDs via surface engineering and in explanations of experimental data. PMID- 27669358 TI - Allosteric Regulation of the Rotational Speed in a Light-Driven Molecular Motor. AB - The rotational speed of an overcrowded alkene-based molecular rotary motor, having an integrated 4,5-diazafluorenyl coordination motif, can be regulated allosterically via the binding of metal ions. DFT calculations have been used to predict the relative speed of rotation of three different (i.e., zinc, palladium, and platinum) metal dichloride complexes. The photochemical and thermal isomerization behavior of these complexes has been studied in detail using UV-vis and 1H NMR spectroscopy. Our results confirm that metal coordination induces a contraction of the diazafluorenyl lower half, resulting in a reduction of the steric hindrance in the "fjord" region of the molecule, which causes an increase of the rotational speed. Importantly, metal complexation can be accomplished in situ and is found to be reversible upon the addition of a competing ligand. Consequently, the rotational behavior of these molecular motors can be dynamically controlled with chemical additives. PMID- 27669359 TI - Controlled Interfacial Permeation, Nanostructure Formation, Catalytic Efficiency, Signal Enhancement Capability, and Cell Spreading by Adjusting Photochemical Cross-Linking Degrees of Layer-by-Layer Films. AB - Interfacial properties including permeation, catalytic efficiency, Raman signal enhancement capabilities, and cell spreading efficiencies are important features that determine material functionality and applications. Here, we propose a facile method to adjust the above-mentioned properties by controlling the cross-linking degrees of multilayer using a photoactive molecule. After treating the cross linked films in basic solutions, films with different cross-linking degrees presented varying residue thicknesses and film morphologies. As a result, these different films possessed distinct molecular loading and release characteristics. In addition, gold nanoparticles (AuNPs) of different morphological traits were generated by redox reactions coupled with diffusion within these films. The AuNP polyelectrolyte obtained from the polyelectrolyte films of the medium cross linking degrees displayed the highest catalytic efficiency and signal enhancement capabilities. Furthermore, cells responded to the variation of film cross-linking degrees, and on the films with the highest cross-linking degree, cells adhered with the highest speed. We expect this report to provide a general interfacial material engineering strategy for material designs. PMID- 27669360 TI - Host-Sensitized and Tunable Luminescence of GdNbO4:Ln3+ (Ln3+ = Eu3+/Tb3+/Tm3+) Nanocrystalline Phosphors with Abundant Color. AB - Up to now, GdNbO4 has always been regarded as an essentially inert material in the visible region with excitation of UV light and electron beams. Nevertheless, here we demonstrate a new recreating blue emission of GdNbO4 nanocrystalline phosphors with a quantum efficiency of 41.6% and host sensitized luminescence in GdNbO4:Ln3+ (Ln3+ = Eu3+/Tb3+/Tm3+) nanocrystalline phosphors with abundant color in response to UV light and electron beams. The GdNbO4 and GdNbO4:Ln3+ (Ln3+ = Eu3+/Tb3+/Tm3+) nanocrystalline phosphors were synthesized by a Pechini-type sol gel process. With excitation of UV light and low-voltage electron beams, the obtained GdNbO4 nanocrystalline phosphor presents a strong blue luminescence from 280 to 650 nm centered around 440 nm, and the GdNbO4:Ln3+ nanocrystalline phosphors show both host emission and respective emission lines derived from the characterize f-f transitions of the doping Eu3+, Tb3+, and Tm3+ ions. The luminescence color of GdNbO4:Ln3+ nanocrystalline phosphors can be tuned from blue to green, red, blue-green, orange, pinkish, white, etc. by varying the doping species, concentration, and relative ratio of the codoping rare earth ions in GdNbO4 host lattice. A single-phase white-light-emission has been realized in Eu3+/Tb3+/Tm3+ triply doped GdNbO4 nanocrystalline phosphors. The luminescence properties and mechanisms of GdNbO4 and GdNbO4:Ln3+ (Ln3+ = Eu3+/Tb3+/Tm3+) are updated. PMID- 27669361 TI - Examination of MMPI-2-RF Substantive Scales as Indicators of Acute Suicidal Affective Disturbance Components. AB - A new suicide-specific diagnostic entity, acute suicidal affective disturbance (ASAD), was recently proposed to fill a void in the nomenclature. Although several studies have examined the reliability, validity, and potential clinical utility of ASAD, no studies have examined personality indicators of ASAD. This study sought to examine the association between personality and psychopathology factors, as assessed by the Minnesota Multiphasic Personality Inventory-2-Revised Form (MMPI-2-RF), and constructs that comprise ASAD in a sample of 554 psychiatric outpatients who completed all measures prior to their intake appointments. A smaller subset of patients (N = 58) also completed a measure designed to assess lifetime ASAD symptoms. Results indicated that ASAD symptoms were associated with traits characterized by emotional turmoil and atypical cognitive processes. Further, suicide-related criteria that comprise ASAD were related to low positive emotionality and hopelessness, whereas the overarousal criteria were associated with somatic symptoms and an inability to tolerate frustration and stress. These findings expand on previous research that examines the convergent and discriminant validity of ASAD and could inform clinical treatment by providing insight into personality traits that might be associated with acute suicide risk. PMID- 27669364 TI - Methods for efficacy evaluations of antibacterial treatments in multiple body site infection trials. AB - Unmet medical need exists for serious bacterial diseases caused by multidrug resistant infections, necessitating an urgent need for newer therapies with greater treatment benefits to patients. For meeting this need, the usual approach has been to conduct separate clinical trials, each trial targeting infection at a single body-site, e.g., for respiratory tract, intra-abdominal site, urinary tract, or blood. However, for the unmet medical need situations, this approach seems inefficient for developing antibacterial drugs with activity against single species or against multiple species of bacteria for a broader indication. Instead, a streamlined clinical development program for such situations can benefit by considering multiple body-site infection trials. Such trials would enroll patients with infections at different body-sites, but with similar severity and comorbidity for avoiding potential treatment effect heterogeneity. Such trials, when properly designed and conducted, can be informative and can save time and resources in drug development. Goals for such trials would be to first demonstrate that there is evidence of an overall treatment effect, and then to show that the treatment effects at individual body-sites reveal consistency in contributing to the overall treatment effect, or to identify a subset of body sites for which greater treatment effect can be supported by a specified statistical decision criterion. For this, we propose here an information-based procedure for the demonstration of treatment effect overall across all body sites, or for a subset of body-sites, on considering two types of error rates of falsely concluding treatment effect. PMID- 27669363 TI - The Association of Health Literacy with Health Behavior, Socioeconomic Indicators, and Self-Assessed Health From a National Adult Survey in Israel. AB - There is a growing need to understand how health literacy influences health outcomes in diverse populations. The aim of this study was to examine the relationship between health literacy, health behavior, sociodemographic indicators, and self-assessed health in the adult population in Israel while identifying populations at risk for low health literacy. A cross-sectional national survey was conducted among 600 adults randomly selected from a national database. The Health Literacy Survey-Europe-Q16 (HLS-EU-Q16) research instrument, adapted for use in Israel, was the basis for home interviews in Hebrew, Russian, and Arabic. Three levels of health literacy were distinguished: More than 31% of the sample had inadequate or problematic health literacy, and 69% showed likely sufficient health literacy. Logistic regression analyses showed that after we controlled for other determinants, years of education (beta = 1.8) and income (beta = 2.2) were significantly associated with health literacy. Multinomial logistic regression analysis showed that health literacy, along with age, was the strongest independent variable associated with self-assessed health. Thus, health literacy, strongly influenced by income and years of education, may play a key role in determining self-assessed health, a proxy health outcome, beyond sociodemographic variables. The study results contribute to understanding the role of health literacy in health disparities and identifying action areas for health promotion. PMID- 27669362 TI - Human Herpesvirus 6 replication predicts Cytomegalovirus reactivation after allogeneic stem cell transplantation from haploidentical donor. AB - BACKGROUND AND OBJECTIVES: Since HHV-6 reactivation after transplant has been reported to increase the risk of CMV infection, we tested this hypothesis in the HLA-haploidentical hematopoietic stem cell transplantation setting. STUDY DESIGN: From February 2011 to October 2015, 75 patients received hematopoietic stem cell transplantation using a T-cell replete graft from a HLA-haploidentical donor at our Institution. RESULTS: Interestingly, 87% of HHV-6 reactivations were followed by a CMV reactivation, at a median of 15days between the two viruses. Incidence of CMV reactivation was 14.5-fold higher in those patients with prior HHV-6 reactivation vs. those without it (p-value<0.001). CONCLUSION: The present results suggest that HHV-6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection. PMID- 27669366 TI - Prenatal diagnosis and early postnatal management of pyriform sinus cyst: experience at a single medical center in mainland China. AB - OBJECTIVE: The aim of this study was to determine whether prenatal diagnosis of pyriform sinus cyst can improve the prognosis of this disorder. METHODS: A retrospective review was performed in 15 neonates with a pyriform sinus cyst seen at a single center between 2010 and 2014. Among the 15 cases, the diagnosis was made prenatally in eight cases (PreD), while the diagnosis was made postnatally in seven cases (PostD). Neonatal outcome was compared in the two subgroups. RESULTS: The mean gestational age at diagnosis of PreD was 27 +/- 6.8 weeks, while the mean age at admission of PostD was 10.1 +/- 8.8 days. Cervical mass, fever, respiratory distress, and hoarseness were common symptoms. The mean duration of postoperative mechanical ventilation was 11.5 +/- 13.9 and 100.71 +/- 80.0 h, respectively, in PreD and PostD (p < 0.01). The average postoperative length of stay and the length of hospital stay were 11.3 +/- 3.34 and 19.6 +/- 4.41 days in PreD, and 15.14 +/- 8.28 and 24.14 +/- 8.51 days in PostD, respectively. CONCLUSION: Prenatal diagnosis and timely postnatal sequential intervention were associated with less complications and shortened duration of postoperative mechanical ventilation. (c) 2016 John Wiley & Sons, Ltd. PMID- 27669365 TI - Environmental nanoparticles are significantly over-expressed in acute myeloid leukemia. AB - The increase in the incidence of acute myeloid leukemia (AML) may suggest a possible environmental etiology. PM2.5 was declared by IARC a Class I carcinogen. No report has focused on particulate environmental pollution together with AML. The study investigated the presence and composition of particulate matter in blood with a Scanning Electron Microscope coupled with an Energy Dispersive Spectroscope, a sensor capable of identifying the composition of foreign bodies. 38 peripheral blood samples, 19 AML cases and 19 healthy controls, were analyzed. A significant overload of particulate matter-derived nanoparticles linked or aggregated to blood components was found in AML patients, while almost absent in matched healthy controls. Two-tailed Student's t-test, MANOVA and Principal Component Analysis indicated that the total numbers of aggregates and particles were statistically different between cases and controls (MANOVA, P<0.001 and P=0.009 respectively). The particles detected showed to contain highly-reactive, non-biocompatible and non-biodegradable metals; in particular, micro- and nano sized particles grouped in organic/inorganic clusters, with statistically higher frequency of a subgroup of elements in AML samples. The demonstration, for the first time, of an overload of nanoparticles linked to blood components in AML patients could be the basis for a possible, novel pathogenetic mechanism for AML development. PMID- 27669367 TI - Exome sequencing reveals novel homozygous FOXE3 mutation in microphthalmos with staphylomatous malformation. PMID- 27669368 TI - Retrospective evaluation of the effect of red blood cell product age on occurrence of acute transfusion-related complications in dogs: 210 cases (2010 2012). AB - OBJECTIVE: To determine whether red blood cell (RBC) product age influences the occurrence of acute transfusion-related complications and mortality in dogs. The hypothesis was that acute transfusion-related complications and mortality would increase with age of product. DESIGN: Retrospective study (2010-2012). SETTING: University teaching hospital. ANIMALS: Two hundred and ten clinical canine patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for dogs receiving RBC-containing products. Patient signalment; reason for transfusion; product type, dose, age, and source; pretransfusion compatibility; rate, route, and method of administration; administration of multiple transfusions; underlying disease; occurrence of transfusion-related complications (eg, fever, hemolysis, gastrointestinal distress, cardiovascular, neurologic, and respiratory complications); various hematologic parameters; and survival were recorded. Data were analyzed for association between potential risk factors and occurrence of transfusion-related complications as well as between transfusion-related complications and survival. Of 333 transfusion events in 210 patients, 84 transfusion-related complications occurred. Fever was most common (41/333), followed by hemolysis (21/333). For every additional day of product age, the odds of hemolysis increased significantly (odds ratio, 1.11; 95% confidence interval, 1.06-1.16; P < 0.0001). Transfusion-related complications when considered as a whole were associated with higher dose of product, longer duration of administration per transfusion event, and immune-mediated disease, but not with source of product or general category of anemia. Administration rate was significantly slower in patients with febrile transfusion-related complications (P < 0.0001). Product age was not associated with increased mortality. CONCLUSIONS: Age of stored RBC products is associated with increased risk of transfusion-related hemolysis, but not with fever. Prospective clinical studies evaluating the influence of storage duration on development of in vitro versus in vivo hemolysis are warranted. PMID- 27669369 TI - Evaluation of insulin sensitivity and secretion in primary aldosteronism. AB - In primary aldosteronism (PA), insulin response to glucose is not fully understood. Insulin action was elucidated using indices in 32 PA and 21 essential hypertension (EH) patients. These patients were evaluated using homeostasis model assessment (HOMA) indices, quantitative insulin sensitivity check index (QUICKI), and insulinogenic index (IGI), which were expressed for insulin sensitivity/secretion and the early phase of insulin secretion. Insulin sensitivity and early phase of insulin secretion were decreased in PA, and there was a negative correlation between serum potassium concentration and insulin sensitivity indices. These findings suggest that glucose intolerance in PA may be caused by hypokalemia-induced insulin resistance and hypokalemia-independent impairment of early-phase insulin secretion. PMID- 27669370 TI - What a Shame: Increased Rates of OMS Resident Burnout May Be Related to the Frequency of Shamed Events During Training. AB - PURPOSE: Shame is an ineffective tool in residency education that often results in depression, isolation, and worse patient care. This study aimed to assess burnout, depersonalization, and personal achievement levels in current oral and maxillofacial surgery (OMS) residents, to assess the prevalence of the use of shame in OMS residency training, and to determine whether there is a relation between shame exposure and resident burnout, depersonalization, and personal achievement levels. MATERIALS AND METHODS: An anonymous 20-question cross sectional survey was developed incorporating the Maslach Burnout Index and a previously validated shame questionnaire and sent to all OMS program directors affiliated with the American Association of Oral and Maxillofacial Surgeons for distribution among their respective residents in 2016. Univariate analyses were used to determine the distribution of the predictor (shame) and outcome (burnout) by gender and by frequency of shaming events. Multivariable logistic regression analysis was used to assess the relation of shame to burnout. A 2-sided P value less than .05 was considered statistically significant. RESULTS: Two hundred seventeen responses were received; 82% of respondents were men (n = 178), 95% were 25 to 34 years old (n = 206), and 58% (n = 126) were enrolled in a 4-year program. Frequently shamed residents were more likely to have depression (58 vs 22%; P < .0001), isolation (55 vs 22%; P < .0001), and poor job performance (50 vs 30%; P < .0001). Residents who were frequently shamed were more likely to experience moderate to severe burnout (odds ratio = 4.6; 95% confidence interval, 2.1-10.0; P < .001) and severe depersonalization (odds ratio = 5.1; 95% confidence interval, 2.1-12.0; P < .0001) than residents who had never or infrequently been shamed. CONCLUSION: There is a clear relation between the number of shame events and burnout and depersonalization levels. It is important to understand the negative impact that the experience of shame has on residents, including its unintended consequences. PMID- 27669371 TI - Intuitive Facial Imaging Method for Evaluation of Postoperative Swelling: A Combination of 3-Dimensional Computed Tomography and Laser Surface Scanning in Orthognathic Surgery. AB - PURPOSE: Postoperative facial swelling after orthognathic surgery may be prolonged and of concern in some patients. In recent years, there have been several reports of analysis of postoperative facial swelling by volume data; however, such evaluations cannot exclude the possibility of error in the measured point because there are no clear anatomic landmarks on the cheek. Three dimensional laser scanning is a noninvasive tool that can be used to measure surface changes in soft tissue over time. The aim of this study was to quantify postoperative swelling in orthognathic surgery by fusing surface scanned images with skin images reconstructed from 3-dimensional computed tomography data and identifying a set of reference points on the bone. MATERIALS AND METHODS: The study comprised 30 patients undergoing bilateral sagittal split osteotomy. Facial scans were obtained with the Artec Eva Scan imaging system (Data Design, Aichi, Japan) at 9 time points from before surgery to 6 months postoperatively. Postoperative scan images were compared with the baseline facial scan obtained 6 months postoperatively. RESULTS: On average, 66% of the initial postoperative edema subsided in 1 month. After 3 months, only 5% of the swelling remained. There were statistically significant correlations between subcutaneous tissue thickness and swelling (P < .0001). CONCLUSIONS: We were able to monitor facial swelling after orthognathic surgery with very high precision using the described method. Subcutaneous tissue thickness is an important determinant of facial swelling. PMID- 27669372 TI - Tooth-Borne Anterior Maxillary Distraction for Cleft Maxillary Hypoplasia: Our Experience With 147 Patients. AB - PURPOSE: To evaluate the results of anterior maxillary distraction for its efficacy and long-term stability in the management of cleft maxillary hypoplasia in a large series of patients with a long-term follow-up extending to 4 years. MATERIALS AND METHODS: One hundred sixty-four patients at least 10 years old with cleft maxillary hypoplasia who presented to the authors' unit from January 2009 through October 2014 were evaluated retrospectively, irrespective of gender, type of cleft lip and palate, and amount of advancement needed. Anterior maxillary distraction using a tooth-borne distractor appliance was carried out in all patients and all patients were followed up to 4 years (range, 1 to 4 yr) to evaluate the stability of the procedure and to document any relapse using digitalized lateral cephalograms taken before distraction, immediately after distraction (T2), and at the last follow-up visit (T3; range, 1 to 4 yr). Seventeen patients were subsequently lost to follow-up; therefore, a complete set of records was available for 147 patients. In a subset of 50 patients, perceptual speech assessment was carried out preoperatively and 6 months postoperatively by 2 speech pathologists using the Perkins scoring system that allowed the evaluation of 5 parameters (velopharyngeal insufficiency, resonance, nasal air emission, articulation, and intelligibility). None of these patients underwent speech therapy during the course of evaluation. The development of complications intra- or postoperatively was noted. The data were tabulated and analyzed. RESULTS: An advancement ranging from 4.0 to 13.1 mm (mean, 9.42 mm) was achieved in all patients. One hundred forty patients (95.23%) showed stable results on lateral cephalograms and when T2 values were compared with T3 values. Seven patients (4.76%) exhibited skeletal relapse in various linear and angular measurements assessed on lateral cephalograms. At 6-month follow-up, improvements of 62% (n = 31), 64% (n = 32), 50% (n = 25), 68% (n = 34), and 70% (n = 35) in velopharyngeal insufficiency, resonance, nasal air emission, articulation, and intelligibility, respectively, were observed, with worsening of all parameters in 1 patient (2%). An overall complication rate of 25.17% (n = 37) was noted, with bleeding being the most common intra- and postoperative complication noted in 15 patients (10.2%). No serious consequences related to any complication were noted. CONCLUSION: Anterior maxillary distraction can be considered a suitable treatment option for the management of mild to moderate cleft maxillary hypoplasia because the anteroposterior deficiency can be addressed at a young age, immediately after the eruption of the maxillary second premolars. Stable long-term results with negligible skeletal relapse are possible with this technique, with an added advantage of unhampered or even improved velopharyngeal function. PMID- 27669373 TI - Prevention of Oral Candidiasis After Free Flap Surgery: Role of 3% Sodium Bicarbonate Saline in Oral Care. AB - PURPOSE: Relevant reports about oral candidiasis status and prevention measures after free flap surgery for the oral and maxillofacial region are limited. The present study explored oral candidiasis status after free flap surgery and its prevention through a prospective comparative study. PATIENTS AND METHODS: One hundred four patients were randomized to a control group (n = 54) and an experimental group (n = 50). Compared with the control group, the experimental group was provided an additional 3% sodium bicarbonate saline solution for oral care after free flap surgery. The incidence of oral candidiasis was evaluated by objective examination (saliva culture and salivary pH measurement) and subjective evaluation (clinical signs of oral candidiasis) at admission and from postoperative days 1 to 14. RESULTS: The salivary pH values of the 2 groups were lower than the normal salivary pH, and postoperative salivary pH values were always lower than the active range of oral lysozymes in the control group. The salivary pH values of the experimental group were higher than those of the control group from postoperative days 6 to 14 (P < .05). The incidence of oral candidiasis was 13.0% in the control group, which was higher than that in the experimental group (2.0%; P < .05). In addition, advanced age, use of a free flap for the simultaneous repair of intraoral and paraoral defects, and a combination of 2 antibiotic types were risk factors for oral candidiasis. CONCLUSION: Oral candidiasis was common in patients after free flap reconstruction surgery, and the use of 3% sodium bicarbonate saline solution for oral care effectively prevented it. PMID- 27669374 TI - Correlations between macrophage polarizing cytokines, inflammatory mediators, osteoclast activity, and toll-like receptors in tissues around aseptically loosened hip implants. AB - Aseptic loosening and osteolysis of joint replacements are driven by macrophage mediated inflammatory reactions to implant-derived wear debris, but many aspects of these events remain poorly characterized. To better understand the relationships among inflammatory and chemotactic mediators, macrophage phenotype and polarizing cytokines, osteoclast activity, and Toll-like receptors (TLRs) in the pathogenesis of aseptic loosening, we determined how the relative expressions of these factors in the peri-implant tissues correlate to each other and to the life span of the implants using Pearson correlation. The expression of pro inflammatory mediators and chemokines showed positive correlations among themselves, and with TLR4. Furthermore, M1-polarizing IFN-gamma showed positive correlations with a number of pro-inflammatory and chemotactic mediators, whereas M2-polarizing IL-4 showed no such association. IL-8 expression significantly correlated with early time to revision. Similar trends were observed for TNF alpha, IFN-gamma, and CCL3, while the opposite was detected for IL-4. However, none of the inflammatory mediators correlated with the markers of osteoclast activity or the RANKL/OPG ratio. The results highlight the importance of the inflammatory mediators, IFN-gamma and TLR4, in the pathogenesis of aseptic loosening; increased pro-inflammatory status was associated with early time to revision, whereas IL-4 correlated with longer implant survival. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 454-463, 2017. PMID- 27669375 TI - Designing a Clean Label Sponge Cake with Reduced Fat Content. AB - The fat in a sponge cake formulation was partially replaced (0%, 30%, 50%, and 70%) with OptiSolTM5300.This natural functional ingredient derived from flax seeds, rich in fiber and alpha-linoleic acid, provides a natural substitute for guar and xanthan gums, avoiding E-numbers on labels. The structure and some physicochemical properties of the formulations were examined, sensory analysis was conducted and changes in starch digestibility due to adding this ingredient were determined. Increasing quantities of OptiSolTM5300 gave harder cakes, with less weight loss during baking, without affecting the final cake height. There were no significant differences (P > 0.05) in texture, flavor and overall acceptance between the control and the 30% substitution cake, nor in the rapidly digestible starch values. Consequently, replacing up to 30% of the fat with OptiSolTM5300 gives a new product with health benefits and a clean label that resembles the full-fat sponge cake. PMID- 27669376 TI - Impact of glycerin and lignosulfonate on biodegradation of high explosives in soil. AB - Soil microcosms were constructed and monitored to evaluate the impact of substrate addition and transient aerobic and anaerobic conditions on TNT, RDX and HMX biodegradation in grenade range soils. While TNT was rapidly biodegraded under both aerobic and anaerobic conditions with and without organic substrate, substantial biodegradation of RDX, HMX, and RDX daughter products was not observed under aerobic conditions. However, RDX and HMX were significantly biodegraded under anaerobic conditions, without accumulation of TNT or RDX daughter products (2-ADNT, 4-ADNT, MNX, DNX, and TNX). In separate microcosms containing grenade range soil, glycerin and lignosulfonate addition enhanced oxygen consumption, increasing the consumption rate >200% compared to untreated soils. Mathematical model simulations indicate that oxygen consumption rates of 5 to 20g/m3/d can be achieved with reasonable amendment loading rates. These results indicate that glycerin and lignosulfonate can be potentially used to stimulate RDX and HMX biodegradation by increasing oxygen consumption rates in soil. PMID- 27669377 TI - Effect of compositional heterogeneity on dissolution of non-ideal LNAPL mixtures. AB - The extent of dissolution of petroleum hydrocarbon fuels into groundwater depends greatly on fuel composition. Petroleum fuels can consist of thousands of compounds creating different interactions within the non-aqueous phase liquid (NAPL), thereby affecting the relative dissolution of the components and hence a groundwater plume's composition over long periods. Laboratory experiments were conducted to study the variability in the effective solubilities and activity coefficients for common constituents of gasoline fuels (benzene, toluene, p xylene and 1,2,4-trimethylbenzene) (BTX) in matrices with an extreme range of molar volumes and chemical affinities. Four synthetic mixtures were investigated comprising BTX with the bulk of the NAPL mixtures made up of either, ethylbenzene (an aromatic like BTX with similar molar volume); 1,3,5-trimethylbenzene (an aromatic with a greater molar volume); n-hexane (an aliphatic with a low molar volume); and n-decane (an aliphatic with a high molar volume). Equilibrium solubility values for the constituents were under-predicted by Raoult's law by up to 30% (higher experimental concentrations) for the mixture with n-hexane as a filler and over-predicted by up to 12% (lower experimental concentrations) for the aromatic mixtures with ethylbenzene and 1,3,5-trimethylbenzene as fillers. Application of PP-LFER (poly-parameter linear free energy relationship) model for non-ideal mixtures also resulted in poor correlation between experimentally measured and predicted concentrations, indicating that differences in chemical affinities can be the major cause of deviation from ideal behavior. Synthetic mixtures were compared with the dissolution behavior of fresh and naturally weathered unleaded gasoline. The presence of lighter aliphatic components in the gasoline had a profound effect on estimating effective solubility due to chemical affinity differences (estimated at 0.0055 per percentage increase in the molar proportion of aliphatic) as well as reduced molar volumes (estimated at -0.0091 in the activity coefficient per unit increase in molar volume, mL/mol). Previously measured changes in activity coefficients due to natural weathering of 0.25 compares well to 0.27 calculated here based on changes in the chemical affinity and molar volumes. The study suggests that the initial estimation of the composition of a fuel is crucial in evaluating dissolution processes due to ideal and non-ideal dissolution, and in predicting long term dissolution trends and the longevity of NAPL petroleum plume risks. PMID- 27669378 TI - Mathematical modeling of simultaneous carbon-nitrogen-sulfur removal from industrial wastewater. AB - A mathematical model of carbon, nitrogen and sulfur removal (C-N-S) from industrial wastewater was constructed considering the interactions of sulfate reducing bacteria (SRB), sulfide-oxidizing bacteria (SOB), nitrate-reducing bacteria (NRB), facultative bacteria (FB), and methane producing archaea (MPA). For the kinetic network, the bioconversion of C-N by heterotrophic denitrifiers (NO3-->NO2-->N2), and that of C-S by SRB (SO42-->S2-) and SOB (S2-->S0) was proposed and calibrated based on batch experimental data. The model closely predicted the profiles of nitrate, nitrite, sulfate, sulfide, lactate, acetate, methane and oxygen under both anaerobic and micro-aerobic conditions. The best fit kinetic parameters had small 95% confidence regions with mean values approximately at the center. The model was further validated using independent data sets generated under different operating conditions. This work was the first successful mathematical modeling of simultaneous C-N-S removal from industrial wastewater and more importantly, the proposed model was proven feasible to simulate other relevant processes, such as sulfate-reducing, sulfide-oxidizing process (SR-SO) and denitrifying sulfide removal (DSR) process. The model developed is expected to enhance our ability to predict the treatment of carbon nitrogen-sulfur contaminated industrial wastewater. PMID- 27669379 TI - Effect of dissimilatory iron and sulfate reduction on arsenic dynamics in the wetland rhizosphere and its bioaccumulation in wetland plants (Scirpus actus). AB - Microbial redox transformations of arsenic (As) are coupled to dissimilatory iron and sulfate reduction in the wetlands, however, the processes involved are complex and poorly defined. In this study, we investigated the effect of dissimilatory iron and sulfate reduction on As dynamics in the wetland rhizosphere and its bioaccumulation in plants using greenhouse mesocosms. Results show that high Fe (50MUM ferrihydrite/g solid medium) and SO42- (5mM) treatments are most favorable for As sequestration in the presence of wetland plants (Scirpus actus), probably because root exudates facilitate the microbial reduction of Fe(III), SO42-, and As(V) to sequester As(III) by incorporation into iron sulfides and/or plant uptake. As retention in the solid medium and accumulation in plants were mainly controlled by SO42- rather than Fe levels. Compared to the low SO42- (0.1mM) treatment, high SO42- resulted in 2 times more As sequestered in the solid medium, 30 times more As in roots, and 49% less As in leaves. An As speciation analysis in pore water indicated that 19% more dissolved As was reduced under high SO42- than low SO42- levels, which is consistent with the fact that more dissimilatory arsenate-respiring bacteria were found under high SO42- levels. PMID- 27669381 TI - Efficient degradation of phenol using iron-montmorillonite as a Fenton catalyst: Importance of visible light irradiation and intermediates. AB - Iron-montmorillonite (Fe-Mt) with delaminated structures was synthesized via the introduction of iron oxides into Na-montmorillonite. Fe-Mt showed significant increases in the available iron content, surface area and pore volume, along with a slight increase in the basal spacing from d001=1.26 (Na-Mt) to 1.53nm (Fe-Mt). The Fenton process was efficient for phenol removal using Fe-Mt as a catalyst under visible light irradiation, and the process had two-stage pseudo-first order kinetics. The overall reaction had a higher degradation rate even when it was only irradiated with visible light for the first 40min period. Further investigation confirmed that the irradiation increased the presence of certain intermediates. Among them, 1,4-benzoquinone, hydroquinone, and catechol all enhanced the Fenton reaction rates. Either catechol or hydroquinone was added to the Fenton system with Fe-Mt/H2O2 with or without visible light irradiation, and they both accelerated phenol degradation because catechol and hydroquinone are capable of reductively and effectively transforming Fe(III) into Fe(II). The concentrations of dissolved total Fe increased with the increase in the oxalic acid concentration, which can strongly chelate Fe(III). Hence, iron was released from Fe-Mt, and reductive transformation played an important role in promoting the Fenton reaction process for phenol removal. PMID- 27669380 TI - The interactions between nanoscale zero-valent iron and microbes in the subsurface environment: A review. AB - Nanoscale zero-valent iron (NZVI) particles, applied for in-situ subsurface remediation, are inevitable to interact with various microbes in the remediation sites directly or indirectly. This review summarizes their interactions, including the effects of NZVI on microbial activity and growth, the synergistic effect of NZVI and microbes on the contaminant removal, and the effects of microbes on the aging of NZVI. NZVI could exert either inhibitive or stimulative effects on the growth of microbes. The mechanisms of NZVI cytotoxicity (i.e., the inhibitive effect) include physical damage and biochemical destruction. The stimulative effects of NZVI on certain bacteria are associated with the creation of appropriate living environment, either through providing electron donor (e.g., H2) or carbon sources (e.g., the engineered organic surface modifiers), or through eliminating the noxious substances that can cause bactericidal consequence. As a result of the positive interaction, the combination of NZVI and some microbes shows synergistic effect on contaminant removal. Additionally, the aged NZVI can be utilized by some iron-reducing bacteria, resulting in the transformation of Fe(III) to Fe(II), which can further contribute to the contaminant reduction. However, the Fe(III)-reduction process can probably induce environmental risks, such as environmental methylation and remobilization of the previously entrapped heavy metals. PMID- 27669382 TI - Utilization of unmodified gold nanoparticles for label-free detection of mercury (II): Insight into rational design of mercury-specific oligonucleotides. AB - Colorimetric detection of mercury (II) with the use of DNA oligonucleotides and unmodified gold nanoparticles (AuNPs) as indicators has been extensively studied. This study provides in-depth insights into the rational design of mercury specific oligonucleotides (MSO) in the biosensing system. The leftover bases of MSO, as a result of the formation of T-Hg2+-T base pairs, can adsorb on the AuNPs and hinder their aggregation at concentrations of salt. This phenomenon was directly verified by the changes in particle sizes characterized by dynamic light scattering for the first time. Based on these findings, we proposed a rational design for the MSO with approximately 20-fold improvement in detection sensitivity. The detection limit of the proposed assay decreased to 15nM with a linear working range from 50nM to 300nM for Hg2+. The cross-reactivity against eight other metal ions was negligible compared with the response to Hg2+. Considering the diverse applications of AuNPs with oligonucleotides, this study can serve as a good reference and provides important implications in sensing and DNA-directed nanoparticle assembly. PMID- 27669383 TI - The impact of alkali metal halide electron donor complexes in the photocatalytic degradation of pentachlorophenol. AB - The performance of photocatalytic oxidation of chemical pollutants is subjected to the presence of anion complexes in natural waters. This study investigated the influence of alkali metal (Na+ (sodium), K+ (potassium)) halides (Cl- (chloride), Br- (bromide), F- (fluoride)) as inorganic ion sources in the photocatalytic degradation of pentachlorophenol (PCP) in batch systems. It was found that the exclusive presence of halides in the absence of an electron acceptor adequately facilitated the photocatalyst process below critical levels of anion populations, where beyond the critical point the process was significantly hindered. Below the determined critical point, the performance in some cases near matches that of the facilitation of the photocatalytic process by exclusive oxygen, acting as an electron scavenger. The coupling of halide ions and oxygenation presented significantly improved photo-oxidation of PCP, this was confirmed by the inclusion of formic acid as a comparative electron donor. The Langmuir Hinshelwood kinetic expression was used to calculate the performance rate kinetics. The probable impact of the halide anions was discussed with regards to the process of electron hole pair recombination prevention. PMID- 27669384 TI - Associations between arsenic in drinking water and the progression of chronic kidney disease: A nationwide study in Taiwan. AB - To evaluate the associations between exposure to arsenic in drinking water and the progression of chronic kidney disease (CKD), we conducted a study in Taiwan. We recruited 8854 participants from a nationwide health screening program from 2000 to 2009 who were at least 20 years old and had two checkups in a 24-month period with at least 12 months apart. We defined CKD as having an estimated glomerular filtration rate (eGFR)<90ml/min/1.73m2 or renal dysfunction demonstrated by proteinuria and a rapid progression of CKD as a decline in eGFR>5ml/min/1.73m2/year. Arsenic levels were assessed on the basis of a governmental nationwide survey. Of the 8854 participants, 1341 exhibited rapid progression. Participants who lived in areas with arsenic levels>=50MUg/L had a higher risk of rapid progression, with an odds ratio of 1.22 (95% confidence interval: 1.05-1.42, p<0.01) after adjusting for hypertension, diabetes mellitus, proteinuria, and anemia. The results showed that a high arsenic level in drinking water was a risk factor for rapid progression of CKD, independent of most of the documented risk factors. Screening and intervention programs should be implemented in endemic areas of exposure to reduce the risk. PMID- 27669385 TI - Inert gas influence on the laminar burning velocity of methane-air mixtures. AB - Flame propagation was studied in methane-air-inert (He, Ar, N2 or CO2) mixtures with various initial pressures and compositions using pressure-time records obtained in a spherical vessel with central ignition. The laminar burning velocities of CH4-air and CH4-air-inert mixtures obtained from experimental p(t) records of the early stage of combustion were compared with literature data and with those obtained from numerical modeling of 1D flames. The overall reaction orders of methane oxidation were determined from the baric coefficients of the laminar burning velocities determined from power-law equations. For all mixtures, the adiabatic flames temperatures were computed, assuming that the chemical equilibrium is reached in the flame front. The overall activation energy for the propagation stage of the combustion process was determined from the temperature dependence of the laminar burning velocity. PMID- 27669386 TI - Detoxification and immobilization of chromite ore processing residue in spinel based glass-ceramic. AB - A promising strategy for the detoxification and immobilization of chromite ore processing residue (COPR) in a spinel-based glass-ceramic matrix is reported in this study. In the search for a more chemically durable matrix for COPR, the most critical crystalline phase for Cr immobilization was found to be a spinel solid solution with a chemical composition of MgCr1.32Fe0.19Al0.49O4. Using Rietveld quantitative X-ray diffraction analysis, we identified this final product is with the phases of spinel (3.5wt.%), diopside (5.2wt.%), and some amorphous contents (91.2wt.%). The partitioning ratio of Cr reveals that about 77% of the Cr was incorporated into the more chemically durable spinel phase. The results of Cr K edge X-ray absorption near-edge spectroscopy show that no Cr(VI) was observed after conversion of COPR into a glass-ceramic, which indicates successful detoxification of Cr(VI) into Cr(III) in the COPR-incorporated glass-ceramic. The leaching performances of Cr2O3 and COPR-incorporated glass-ceramic were compared with a prolonged acid-leaching test, and the results demonstrate the superiority of the COPR-incorporated glass-ceramic matrix in the immobilization of Cr. The overall results suggest that the use of affordable additives has potential in more reliably immobilizing COPR with a spinel-based glass-ceramic for safer disposal of this hazardous waste. PMID- 27669387 TI - Toxicity of 2,6-dichloro-1,4-benzoquinone and five regulated drinking water disinfection by-products for the Caenorhabditis elegans nematode. AB - Scarce toxicological data are available for 2,6-dichloro-1,4-benzoquinone (DCBQ), an emerging water disinfection by-product (DBP) that is of potential public health concern. This study investigated the effects of DCBQ on the lethality, respiration rate, and DNA damage in the Caenorhabditis elegans nematode. Meanwhile, the toxic effects of five regulated DBPs, dichloroacetic acid (DCA), trichloroacetic acid (TCA), monobromoacetic acid (MBA), dibromoacetic acid (DBA), and N-nitrosodimethylamine (NDMA), have also been evaluated. The tested DBPs increased the lethality and inhibited the respiration of C. elegans with an identical order of toxicity as follows: DCBQ>MBA>DBA>DCA>TCA>NDMA. The EC50 value (median concentration causing 50% reduction in respiration compared with untreated C. elegans) is at least 30-fold lower than the corresponding LC50 value (median lethal concentration). Exposure to DCBQ and NDMA, but not to MBA, DBA, DCA, or TCA, resulted in DNA damage to C. elegans. The study suggested that DCBQ was more potent in inducing general toxicity than some regulated DBPs, and it revealed the in vivo genotoxic effect of DCBQ. Furthermore, the C. elegans-based bioassays may provide potentially useful tools for the toxicology assessment and ranking of DBPs. PMID- 27669388 TI - Rose-like I-doped Bi2O2CO3 microspheres with enhanced visible light response: DFT calculation, synthesis and photocatalytic performance. AB - Based on the crystal structure and the DFT calculation of Bi2O2CO3, I- can partly replace the CO32-in Bi2O2CO3 to narrow its bandgap and to enhance its visible light absorption. With this in mind, rose-like I-doped Bi2O2CO3 microspheres were prepared via a hydrothermal process. This method can also be extended to synthesize rose-like Cl- or Br-doped Bi2O2CO3 microspheres. Photoelectrochemical test supports the DFT calculation result that I- doping narrows the bandgap of Bi2O2CO3 by forming two intermediate levels in its forbidden band. Further study reveals that I-doped Bi2O2CO3 microspheres with optimized composition exhibit the best photocatalytic activity. Rhodamine B can be completely degraded within 6min and about 90% of Cr(VI) can be reduced after 25min under the irradiation of visible light (lambda>400nm). PMID- 27669390 TI - Ionic liquid technology to recover volatile organic compounds (VOCs). AB - Volatile organic compounds (VOCs) comprise a wide variety of carbon-based materials which are volatile at relatively low temperatures. Most of VOCs pose a hazard to both human health and the environment. For this reason, in the last years, big efforts have been made to develop efficient techniques for the recovery of VOCs produced from industry. The use of ionic liquids (ILs) is among the most promising separation technologies in this field. This article offers a critical overview on the use of ionic liquids for the separation of VOCs both in bulk and in immobilized form. It covers the most relevant works within this field and provides a global outlook on the limitations and future prospects of this technology. The extraction processes of VOCs by using different IL-based assemblies are described in detail and compared with conventional methods This review also underlines the advantages and limitations posed by ionic liquids according to the nature of the cation and the anions present in their structure and the stability of the membrane configurations in which ILs are used as liquid phase. PMID- 27669389 TI - Adsorption of Cu2+ and Zn2+ by extracellular polymeric substances (EPS) in different sludges: Effect of EPS fractional polarity on binding mechanism. AB - Extracellular polymeric substances (EPS) in sludge samples played a major role in heavy metals removal during wastewater treatment. In this study, the binding quality, adsorption mechanism, as well as the chemical fractional contribution of the sludge EPS from activated sludge, anaerobic granular sludge and anaerobic flocculent sludge to the adsorption of Zn2+ and Cu2+ was investigated. For all three sludge samples, Cu2+ could be more easily adsorbed than Zn2+, and EPS extracted from the anaerobic granular sludge exhibited a relatively higher adsorption capacity than that of anaerobic flocculent sludge and activated sludge. Specifically, hydrophobic EPS of the activated sludge and anaerobic flocculent sludge was more efficient in adsorbing Cu2+ and Zn2+ than that of the hydrophilic EPS. However, hydrophilic EPS in anaerobic granular sludge played a greater role in heavy metals removal. The adsorption of those two heavy metals onto the unfractionated and hydrophobic EPS could be better described by the Langmuir isotherm, while Freundlich models fitted hydrophilic EPS. In addition, the effect of the heavy metals adsorption on the spectrum characteristics of the sludge EPS was also explored by analysis of FT-IR and fluorescent spectra. PMID- 27669391 TI - Simultaneous removal of multi-pollutants from flue gas by a vaporized composite absorbent. AB - An economical process that was used to remove SO2, NO and Hg0 simultaneously was developed, based on the pre-oxidations of Hg0 and NO by a vaporized Fenton-based complex oxidant (FO) consisted of Fenton and NaClO. The effects of concentrations of FeSO4 and NaClO in the oxidant, the molar ratio of vaporized oxidant to multi pollutant, the oxidant solution pH, the reaction temperature, the gas flow ratio of vaporized FO to multi-pollutants, the flue gas flow and the concentrations of coexistence gases in flue gas on the simultaneous removals were investigated experimentally. The results showed that the removals of NO and Hg0 were significantly depended on FeSO4 and NaClO concentrations, the molar ratio of vaporized oxidant to multi-pollutants, the FO solution pH, the reaction temperature, the gas flow ratio of vaporized FO to multi-pollutants and flue gas flow. And higher concentration of SO2 and an appropriate concentration of NO had the promotion for Hg0 removal. The average simultaneous removal efficiencies of 100% for SO2, 81% for NO and 91% for Hg0 were obtained under the optimal reaction conditions. According to the characterization of the reaction removal products by SEM, EDS, XRD and AFS, the reaction mechanism was speculated. PMID- 27669392 TI - Understanding and exploring the potentials of household water treatment methods for volatile disinfection by-products control: Kinetics, mechanisms, and influencing factors. AB - This study systematically evaluates the capabilities of five types of household water treatment (HWT) methods (including boiler heating, microwave irradiation, pouring, stirring, and shaking) on the removals of four regulated trihalomethanes (THM4) and three iodinated halomethanes (IHMs) under a variety of conditions simulative of residential uses. Overall, the results clearly showed promising capabilities of all five HWT methods in controlling volatile disinfection by products (DBPs), and heating with a boiler was the most effective approach among all methods due to the synergistic effects of water turbulence and bubbling phenomena. A contemporary boiler equipped with an automatic switch-off function reduced on average 92% of seven halomethanes (HM7) at favourable conditions. The removal increased significantly with increasing initial concentrations and the rates correlated well with the logarithmic Henry's law constants and molecular weights of compounds, with triiodomethane being the most refractory species. Meanwhile, the importance of water handling habits was revealed, including power input, operation time, volume, heating/cooling speed, cooling method, and capping conditions. The findings hence explored the potentials of HWTs on DBP control and pointed out a potential limit to DBP epidemiology studies that do not consider water handling habits. PMID- 27669393 TI - Process evaluation of a preschool physical activity intervention using web-based delivery. AB - BACKGROUND AND PURPOSE: Preschool/childcare settings offer a practical target for physical activity interventions. Online learning programs have the potential for greater public health reach and impact. The SHAPES-Dissemination (SHAPES-D) project adapted the original SHAPES in-person intervention for online delivery to teachers. The purpose of this paper is to describe the implementation monitoring and process evaluation for the SHAPES-D project. METHODS: Nine preschools with 26 classrooms participated. A total of 41 teachers were trained via online learning to implement the SHAPES-D program in their classrooms. The dose received, completeness, and fidelity of implementation were assessed through website metrics, teacher surveys and interviews, and classroom observations. RESULTS: Dose received was adequate (73%). Observed completeness and physical activity enjoyment fidelity were high (100%), although moderate-to-vigorous physical activity fidelity and social environment fidelity were low (25% each). Overall implementation was high (91%). DISCUSSION: Results indicate that the online method of delivery is viable for dissemination. The online delivery system provides an easy method of monitoring dose received. This may be the first structural intervention to monitor dose received through web metrics. CONCLUSION: The adaptation of an in-person intervention to an online delivery system increases the potential for dissemination of a successful program to increase physical activity in preschool settings. PMID- 27669394 TI - A participatory evaluation framework in the establishment and implementation of transdisciplinary collaborative centers for health disparities research. AB - OBJECTIVE: We describe the formulation and implementation of a participatory evaluation plan for three Transdisciplinary Collaborative Centers for Health Disparities Research funded by the National Institute of Minority Health and Health Disparities. METHODS: Although different in scope of work, all three centers share a common goal of establishing sustainable centers in health disparities science in three priority areas - social determinants of health, men's health research, and health policy research. RESULTS: The logic model guides the process, impact, and outcome evaluation. Emphasis is placed on process evaluation in order to establish a "blue print" that can guide other efforts as well as assure that activities are being implemented as planned. CONCLUSION: We have learned three major lessons in this process: (1) Significant engagement, participation, and commitment of all involved is critical for the evaluation process; (2) Having a "roadmap" (logic model) and "directions" (evaluation worksheets) are instrumental in getting members from different backgrounds to follow the same path; and (3) Participation of the evaluator in the leadership and core meetings facilitates continuous feedback. PMID- 27669395 TI - A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells. AB - OBJECTIVE: Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70% lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). STUDY DESIGN: The impact of 5-HT1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT1B antagonist. RESULTS: 5-HT1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (alpha-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. CONCLUSION: Our findings show for the first time that 5-HT1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT1B expression and antagonists should be further investigated in leiomyoma tumors. PMID- 27669396 TI - Drought increases cowpea (Vigna unguiculata [L.] Walp.) susceptibility to cowpea severe mosaic virus (CPSMV) at early stage of infection. AB - The physiological and biochemical responses of a drought tolerant, virus susceptible cowpea genotype exposed to drought stress (D), infected by Cowpea severe mosaic virus (CPSMV) (V), and to these two combined stresses (DV), at 2 and 6 days post viral inoculation (DPI), were evaluated. Gas exchange parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO2 partial pressure) were reduced in D and DV at 2 and 6 DPI compared to control plants (C). Photosynthesis was reduced by stomatal and biochemical limitations. Water use efficiency increased at 2 DPI in D, DV, and V, but at 6 DPI only in D and DV compared to C. Photochemical parameters (effective quantum efficiency of photosystem II and electron transport rate) decreased in D and DV compared to C, especially at 6 DPI. The potential quantum efficiency of photosystem II did not change, indicating reversible photoinhibition of photosystem II. In DV, catalase decreased at 2 and 6 DPI, ascorbate peroxidase increased at 2 DPI, but decreased at 6 DPI. Hydrogen peroxide increased at 2 and 6 DPI. Peroxidase increased at 6 DPI and chitinase at 2 and 6 DPI. beta-1,3-glucanase decreased in DV at 6 DPI compared to V. Drought increased cowpea susceptibility to CPSMV at 2 DPI, as verified by RT-PCR. However, at 6 DPI, the cowpea plants overcome this effect. Likewise, CPSMV increased the negative effects of drought at 2 DPI, but not at 6 DPI. It was concluded that the responses to combined stresses are not additive and cannot be extrapolated from the study of individual stresses. PMID- 27669397 TI - GhCaM7-like, a calcium sensor gene, influences cotton fiber elongation and biomass production. AB - Calcium signaling regulates many developmental processes in plants. Calmodulin (CaM) is one of the most conserved calcium sensors and has a flexible conformation in eukaryotes. The molecular functions of CaM are unknown in cotton, which is a major source of natural fiber. In this study, a Gossypium hirsutum L.CaM7-like gene was isolated from upland cotton. Bioinformatics analysis indicated that the GhCaM7-like gene was highly conserved as compared with Arabidopsis AtCaM7. The GhCaM7-like gene showed a high expression level in elongating fibers. Expression of beta-glucuronidase was observed in trichomes on the stem, leaf and root in transgenic Arabidopsis plants of a PROGhCaM7-like:GUS fusion. Silencing of the GhCaM7-like gene resulted in decreased fiber length, but also caused reduction in stem height, leaf dimensions, seed length and 100-seed weight, in comparison with those of the control. Reduced expression of the GhCaM7 like gene caused decreased Ca2+ influx in cells of the leaf hypodermis and stem apex, and down-regulation of GhIQD1 (IQ67-domain containing protein), GhAnn2 (Annexins) and GhEXP2 (Expansin). These results indicate that the GhCaM7-like gene plays a vital role in calcium signaling pathways, and may regulate cotton fiber elongation and biomass production by affecting Ca2+ signatures and downstream signaling pathways of CaM. PMID- 27669399 TI - The International Association of Student Surgical Societies: creation and dissemination. AB - SUMMARY: While initiatives exist to address the worldwide need for surgeons, none involve a student-driven solution from low- and middle-income countries (LMICs). In response to falling surgical residency enrolment in South Africa, the students at the University of Cape Town (UCT) founded the UCT Surgical Society and were subsequently instrumental in creating the International Association of Student Surgical Societies (IASSS). The IASSS currently includes 25 societies in 15 countries. Its primary objectives are building sustainable networks for mutually beneficial exchanges, supporting student-driven projects, understanding issues impacting student interest in surgery, promoting global fellowship, creating an elective database and providing assistance to student surgical societies. The IASSS is a unique student-led initiative trying to improve surgical care in LMICs. PMID- 27669398 TI - Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria. AB - Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs. PMID- 27669400 TI - Hypertrophic pyloric stenosis in the Maritimes: examining the waves of change over time. AB - BACKGROUND: Changing patterns of referral and management of pediatric surgical conditions, including hypertrophic pyloric stenosis (HPS), have recently been described and often relate to comfort with early nonoperative management, anesthesia and corrective surgery. Travelling distance required for treatment at pediatric centres can also be burdensome for families. We assessed referral patterns for HPS in the maritime provinces of Canada over 10 years to quantify the burden on families travelling for surgical care. METHODS: We reviewed the charts of all patients with HPS in the Maritimes. Length of hospital stay (LOS) and complication rates were analyzed in regards to resuscitation and management at a pediatric centre and/or peripheral centres. We used postal codes for each patient to track distance travelled for management. RESULTS: We assessed 751 cases of HPS. During the study period (Jan. 1, 2001-Dec. 31, 2010), referral to pediatric centres increased from 49% to 71%. Postoperative complications were 2.5 fold higher in peripheral centres. Infants referred to pediatric centres were 78% less likely to have an LOS longer than 3 days. Laparoscopic pyloromyotomy, which was performed only in pediatric centres, was associated with a shorter postoperative LOS. CONCLUSION: Our study supports the current literature demonstrating improved outcomes, shorter overall LOS and decreased risk of complications when infants with HPS are treated in pediatric centres. This should be considered when planning access to pediatric surgical resources. PMID- 27669401 TI - Preoperative repeat endoscopy for colorectal cancer: What is its role and when is it necessary? AB - SUMMARY: Many surgeons consider repeat endoscopy to be the standard of care for colorectal cancer; however, its utility in the preoperative setting is not well understood, especially given the lack of standardized guidelines on appropriate tumour localization and colonoscopic reporting. This often results in patients undergoing an unnecessary medical procedure during their preoperative evaluation. We discuss some of the issues surrounding the practice of preoperative repeat endoscopy as well as patient perspectives on the procedure. Our observations suggest that repeat endoscopy in the setting of colorectal cancer surgery may play a role in enabling transition of patient care between the initial endoscopist and the treating surgeon and in improving the patient experience. Patients with operable colorectal cancer appear to understand and support the current use of repeat endoscopy. However, improving preoperative care will require further research and ultimately the development of evidence-based clinical guidelines. PMID- 27669402 TI - Sustainability of a proactive geriatric trauma consultation service. AB - BACKGROUND: Proactive geriatric trauma consultation service (GTCS) models have been associated with better delivery of geriatric care and functional outcomes. Whether such collaborative models can be improved and sustained remains uncertain. We describe the sustainability and process improvements of an inpatient GTCS. METHODS: We assessed workflow using interviews and surveys to identify opportunities to optimize the referral process for the GTCS. Sustainability of the service was assessed via a prospective case series (July 2012-December 2013). Study data were derived from a review of the medical record and trauma registry database. Metrics to determine sustainability included volume of cases, staffing levels, rate of adherence to recommendations, geriatric specific clinical outcomes, trauma quality indicators, consultation requests and discharge destination. RESULTS: Through process changes, we were able to ensure every eligible patient was referred for a comprehensive geriatric assessment. Compared with the implementation phase, volume of assessments increased and recommendation adherence rates were maintained. Delirium and/or dementia were the most common geriatric issue addressed. The rate of adherence to recommendations made by the GTCS team was 88.2%. Only 1.4% of patients were discharged to a nursing home. CONCLUSION: Workflow assessment is a useful means to optimize the referral process for comprehensive geriatric assessment. Sustainability of a GTCS was shown by volume, staffing and recommendation adherence. PMID- 27669403 TI - Sustainability of a proactive geriatric trauma consultation service. AB - BACKGROUND: Proactive geriatric trauma consultation service (GTCS) models have been associated with better delivery of geriatric care and functional outcomes. Whether such collaborative models can be improved and sustained remains uncertain. We describe the sustainability and process improvements of an inpatient GTCS. METHODS: We assessed workflow using interviews and surveys to identify opportunities to optimize the referral process for the GTCS. Sustainability of the service was assessed via a prospective case series (July 2012-December 2013). Study data were derived from a review of the medical record and trauma registry database. Metrics to determine sustainability included volume of cases, staffing levels, rate of adherence to recommendations, geriatric specific clinical outcomes, trauma quality indicators, consultation requests and discharge destination. RESULTS: Through process changes, we were able to ensure every eligible patient was referred for a comprehensive geriatric assessment. Compared with the implementation phase, volume of assessments increased and recommendation adherence rates were maintained. Delirium and/or dementia were the most common geriatric issue addressed. The rate of adherence to recommendations made by the GTCS team was 88.2%. Only 1.4% of patients were discharged to a nursing home. CONCLUSION: Workflow assessment is a useful means to optimize the referral process for comprehensive geriatric assessment. Sustainability of a GTCS was demonstrated by volume, staffing and recommendation adherence. PMID- 27669404 TI - Use of intraosseous devices in trauma: a survey of trauma practitioners in Canada, Australia and New Zealand. AB - BACKGROUND: Although used primarily in the pediatric population for decades, the use of intraosseous (IO) devices in the resuscitation of severely injured adult trauma patients has recently become more commonplace. The objective of this study was to determine the experience level, beliefs and attitudes of trauma practitioners in Canada, Australia and New Zealand regarding the use of IO devices in adult trauma patients. METHODS: We administered a web-based survey to all members of 4 national trauma and emergency medicine organizations in Canada, Australia and New Zealand. Survey responses were analyzed using descriptive statistics, univariate comparisons and a proportional odds model. RESULTS: Overall, 425 of 1771 members completed the survey, with 375 being trauma practitioners. IO devices were available to 97% (353 of 363), with EZ-IO being the most common. Nearly all physicians (98%, 357 of 366) had previous training with IO devices, and 85% (223 of 261) had previously used an IO device in adult trauma patients. Most respondents (79%, 285 of 361) were very comfortable placing an IO catheter in the proximal tibia. Most physicians would always or often use an IO catheter in a patient without intravenous access undergoing CPR for traumatic cardiac arrest (84%, 274 of 326) or in a hypotensive patient (without peripheral intravenous access) after 2 attempts or 90 s of trying to establish vascular access (81%, 264 of 326). CONCLUSION: Intraosseous devices are readily available to trauma practitioners in Canada, Australia and New Zealand, and most physicians are trained in device placement. Most physicians surveyed felt comfortable using an IO device in resuscitation of adult trauma patients and would do so for indications broader than current guidelines. PMID- 27669406 TI - Effects of cigarette smoking on cortical thickness in major depressive disorder. AB - Findings of surface-based morphometry studies in major depressive disorder (MDD) are still inconsistent. Given that cigarette smoking is highly prevalent in MDD and has documented negative effects on the brain, it is possible that some of the inconsistencies may be partly explained by cigarette use. The aim of the current study was to examine the influence of cigarette smoking on brain structure in MDD. 50 MDD patients (25 smokers and 25 non-smokers) and 22 age, education, gender and BMI matched non-smoker healthy controls underwent structural magnetic resonance imaging. Thickness and area of the cortex were measured using surface based morphometry implemented with Freesurfer (v5.3.0). The non-smoker MDD patients had significantly increased cortical thickness, including in the left temporal cortex (p < 0.001), right insular cortex (p = 0.033) and left pre- and postcentral gyrus (p = 0.045), compared to healthy controls. We also found decreased cortical thickness in MDD patients who smoked compared to non-smoking patients in regions that overlapped with the regions found to be increased in non smoking patients in comparison to controls. Non-smoker MDD patients had increased surface area in the right lateral occipital cortex (p = 0.009). We did not find any region where cortical thickness or surface area significantly differed between controls and either smoker MDD patients or all MDD patients. The findings of the current study suggest that cigarette smoking is associated with cortical thinning in regions found to be increased in patients with MDD. However, these results should be considered preliminary due to methodological limitations. PMID- 27669405 TI - Aberrant adhesion impacts early development in a Dictyostelium model for juvenile neuronal ceroid lipofuscinosis. AB - Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease, refers to a group of severe neurodegenerative disorders that primarily affect children. The most common subtype of the disease is caused by loss-of-function mutations in CLN3, which is conserved across model species from yeast to human. The precise function of the CLN3 protein is not known, which has made targeted therapy development challenging. In the social amoeba Dictyostelium discoideum, loss of Cln3 causes aberrant mid-to-late stage multicellular development. In this study, we show that Cln3-deficiency causes aberrant adhesion and aggregation during the early stages of Dictyostelium development. cln3- cells form ~30% more multicellular aggregates that are comparatively smaller than those formed by wild type cells. Loss of Cln3 delays aggregation, but has no significant effect on cell speed or cAMP-mediated chemotaxis. The aberrant aggregation of cln3- cells cannot be corrected by manually pulsing cells with cAMP. Moreover, there are no significant differences between wild-type and cln3- cells in the expression of genes linked to cAMP chemotaxis (e.g., adenylyl cyclase, acaA; the cAMP receptor, carA; cAMP phosphodiesterase, pdsA; g-protein alpha 9 subunit, gpaI). However, during this time in development, cln3- cells show reduced cell-substrate and cell cell adhesion, which correlate with changes in the levels of the cell adhesion proteins CadA and CsaA. Specifically, loss of Cln3 decreases the intracellular level of CsaA and increases the amount of soluble CadA in conditioned media. Together, these results suggest that the aberrant aggregation of cln3- cells is due to reduced adhesion during the early stages of development. Revealing the molecular basis underlying this phenotype may provide fresh new insight into CLN3 function. PMID- 27669407 TI - Hippocampal and amygdala volumes in adults with posttraumatic stress disorder secondary to childhood abuse or maltreatment: A systematic review. AB - We systematically reviewed differences in hippocampal and amygdala volumes between adults with childhood maltreatment-related posttraumatic stress disorder (PTSD) and healthy controls. Using the terms "adults", "MRI", "magnetic resonance imaging", with "posttraumatic stress disorder" "PTSD", "child abuse", and "child maltreatment", we conducted searches on several electronic databases. We identified 10 studies that met our inclusion criteria; 7 of which were included in a meta-analysis of hippocampal volume and 4 that were included in a meta analysis of amygdala volume. Mean hippocampal and amygdala volumes were used to determine effect sizes. We found bilateral reduction of both the hippocampus and amygdala in the PTSD group compared to healthy controls, with effect sizes of 0.66 and -0.67 for the left and right hippocampus (p<0.00001 and p=0.002) and 1.08 and -1.15 for the left and right amygdala, (p=0.013 and p=0.003), respectively. Confidence intervals were -0.93,-0.39 and -1.26,-0.29 for the left and right hippocampus, respectively. For the amygdala, confidence intervals were 1.92,-0.23 and -1.19, -0.39 for the left and right amygdala. The relatively few studies available for analysis is a limitation. Additionally, sex diverse MRI studies in PTSD are needed to determine whether sex plays a significant role in the hippocampal effects associated with childhood-onset trauma. PMID- 27669411 TI - Barriers to adult immunization and solutions: Personalized approaches. AB - Immunization is an important component of preventive healthcare services aiming to prevent and eventually eradicate infectious diseases by immunizing people before they become infected. Although immunization is an integral part of children's healthcare, this fact is underrated, even ignored in adults. In Turkey, adult immunization is available only for certain high risk groups such as health care professionals and populations aged > 65 y and under certain conditions including pregnancy, military service, travel-pilgrimage, and employment procedures. The fact that diseases such as pneumococcal pneumonia, influenza, rubeola, varicella, hepatitis A, and tetanus, which could be associated with severe complications in adults, are vaccine-preventable indicates the importance of adult immunization. In addition to the healthcare providers' knowledge about immunization, effective policies of related professional associations and the management of this issue by regulatory authorities, people's awareness in protecting their own health is of utmost importance in achieving the targeted level of adult immunization. This article focuses on the characteristics of the individuals as one of the 3 main cornerstones (individual, healthcare providers, regulatory authorities and supporting organizations) of immunization practices and discusses barriers to adult immunization and recommends solutions. PMID- 27669409 TI - Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval. AB - Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. PMID- 27669408 TI - Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy. AB - A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance. PMID- 27669410 TI - Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons. AB - Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping striatal output. Schemes of basal ganglia circuit dynamics generally consider striatal PV+ interneurons to be homogenous, despite considerable heterogeneity in both form and function. We demonstrate that the selective co-expression of another calcium-binding protein, secretagogin (Scgn), separates PV+ interneurons in rat and primate striatum into two topographically-, physiologically- and structurally-distinct cell populations. In rats, these two interneuron populations differed in their firing rates, patterns and relationships with cortical oscillations in vivo. Moreover, the axons of identified PV+/Scgn+ interneurons preferentially targeted the somata of SPNs of the so-called 'direct pathway', whereas PV+/Scgn- interneurons preferentially targeted 'indirect pathway' SPNs. These two populations of interneurons could therefore provide a substrate through which either of the striatal output pathways can be rapidly and selectively inhibited to subsequently mediate the expression of behavioral routines. PMID- 27669412 TI - Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3). AB - Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates. A second pathway mediating necrosis involves Receptor-Interacting Serine-Threonine Kinase 3 (RIPK3); in this study we sought to investigate the impact of RIPK3 on the development of lupus and nephritis in both sexes. To this end, we used two inducible murine models of lupus: chronic graft versus host disease (cGvHD) and pristane-induced lupus; and nephrotoxic serum (NTS)-induced nephritis as a model of immune mediated nephropathy. We found that the absence of RIPK3 has neither positive nor negative impact on the disease development or progression of lupus and nephritis in all three models, and in both male and female mice. We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease. PMID- 27669413 TI - Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors. AB - Next generation bioreactors are being developed to generate multiple human cell based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology [1, 2]. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilaginous in nature, while the other is osseous. We next develop a general computational approach to model the microfluidics of a multi-chamber, interconnected system that may be applied to human-on-chip devices. This objective requires overcoming several challenges at the level of computational modeling. The main one consists of addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media. Fluid dynamics is also coupled with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living tissues and C constructs. Ultimately, we aim at providing a predictive approach useful for the general organ-on-chip community. To this end, we have developed a lumped parameter approach that allows us to analyze the behavior of multi-unit bioreactor systems with modest computational effort, provided that the behavior of a single unit can be fully characterized. PMID- 27669414 TI - Testing violations of the exponential assumption in cancer clinical trials with survival endpoints. AB - Personalized cancer therapy requires clinical trials with smaller sample sizes compared to trials involving unselected populations that have not been divided into biomarker subgroups. The use of exponential survival modeling for survival endpoints has the potential of gaining 35% efficiency or saving 28% required sample size (Miller, 1983), making personalized therapy trials more feasible. However, the use of exponential survival has not been fully accepted in cancer research practice due to uncertainty about whether or not the exponential assumption holds. We propose a test for identifying violations of the exponential assumption using a reduced piecewise exponential approach. Compared with an alternative goodness-of-fit test, which suffers from inflation of type I error rate under various censoring mechanisms, the proposed test maintains the correct type I error rate. We conduct power analysis using simulated data based on different types of cancer survival distribution in the SEER registry database, and demonstrate the implementation of this approach in existing cancer clinical trials. PMID- 27669415 TI - Multilocus Variable Number of Tandem Repeat Analysis Reveals Multiple Introductions in Spain of Xanthomonas arboricola pv. pruni, the Causal Agent of Bacterial Spot Disease of Stone Fruits and Almond. AB - Xanthomonas arboricola pv. pruni is the causal agent of the bacterial spot disease of stone fruits, almond and some ornamental Prunus species. In Spain it was first detected in 2002 and since then, several outbreaks have occurred in different regions affecting mainly Japanese plum, peach and almond, both in commercial orchards and nurseries. As the origin of the introduction(s) was unknown, we have assessed the genetic diversity of 239 X. arboricola pv. pruni strains collected from 11 Spanish provinces from 2002 to 2013 and 25 reference strains from international collections. We have developed an optimized multilocus variable number of tandem repeat analysis (MLVA) scheme targeting 18 microsatellites and five minisatellites. A high discriminatory power was achieved since almost 50% of the Spanish strains were distinguishable, confirming the usefulness of this genotyping technique at small spatio-temporal scales. Spanish strains grouped in 18 genetic clusters (conservatively delineated so that each cluster contained haplotype networks linked by up to quadruple-locus variations). Furthermore, pairwise comparisons among populations from different provinces showed a strong genetic differentiation. Our results suggest multiple introductions of this pathogen in Spain and redistribution through contaminated nursery propagative plant material. PMID- 27669418 TI - Roger Y. Tsien 1952-2016. PMID- 27669417 TI - Structural basis for precursor protein-directed ribosomal peptide macrocyclization. AB - Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved alpha-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein-protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds. PMID- 27669416 TI - Reproducibility of Search Strategies Is Poor in Systematic Reviews Published in High-Impact Pediatrics, Cardiology and Surgery Journals: A Cross-Sectional Study. AB - BACKGROUND: A high-quality search strategy is considered an essential component of systematic reviews but many do not contain reproducible search strategies. It is unclear if low reproducibility spans medical disciplines, is affected by librarian/search specialist involvement or has improved with increased awareness of reporting guidelines. OBJECTIVES: To examine the reporting of search strategies in systematic reviews published in Pediatrics, Surgery or Cardiology journals in 2012 and determine rates and predictors of including a reproducible search strategy. METHODS: We identified all systematic reviews published in 2012 in the ten highest impact factor journals in Pediatrics, Surgery and Cardiology. Each search strategy was coded to indicate what elements were reported and whether the overall search was reproducible. Reporting and reproducibility rates were compared across disciplines and we measured the influence of librarian/search specialist involvement, discipline or endorsement of a reporting guideline on search reproducibility. RESULTS: 272 articles from 25 journals were included. Reporting of search elements ranged widely from 91% of articles naming search terms to 33% providing a full search strategy and 22% indicating the date the search was executed. Only 22% of articles provided at least one reproducible search strategy and 13% provided a reproducible strategy for all databases searched in the article. Librarians or search specialists were reported as involved in 17% of articles. There were strong disciplinary differences on the reporting of search elements. In the multivariable analysis, only discipline (Pediatrics) was a significant predictor of the inclusion of a reproducible search strategy. CONCLUSIONS: Despite recommendations to report full, reproducible search strategies, many articles still do not. In addition, authors often report a single strategy as covering all databases searched, further decreasing reproducibility. Further research is needed to determine how disciplinary culture may encourage reproducibility and the role that journal editors and peer reviewers could play. PMID- 27669420 TI - Training the Workforce for 21st-Century Science. PMID- 27669419 TI - Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat. AB - We describe a two-dimensional thermal proteome profiling strategy that can be combined with an orthogonal chemoproteomics approach to enable comprehensive target profiling of the marketed histone deacetylase inhibitor panobinostat. The N-hydroxycinnamide moiety is identified as critical for potent and tetrahydrobiopterin-competitive inhibition of phenylalanine hydroxylase leading to increases in phenylalanine and decreases in tyrosine levels. These findings provide a rationale for adverse clinical observations and suggest repurposing of the drug for treatment of tyrosinemia. PMID- 27669421 TI - Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells. AB - INTRODUCTION: Glioblastoma is the most malignant brain tumor in adults and is associated with poor survival despite multimodal treatments. Glioma stem-like cells (GSCs) are cells functionally defined by their self-renewal potential and the ability to reconstitute the original tumor upon orthotopic implantation. They have been postulated to be the culprit of glioma chemo- and radio-resistance ultimately leading to relapse. Understanding the molecular circuits governing the GSC compartment is essential. SOX2, a critical transcription regulator of embryonic and neural stem cell function, is deregulated in GSCs however; the precise molecular pathways regulated by this gene in GSCs remain poorly understood. RESULTS: We performed a genome-wide analysis of SOX2-regulated transcripts in GSCs, using a microarray. We identified a total of 2048 differentially expressed coding transcripts and 261 non-coding transcripts. Cell adhesion and cell-cell signaling are among the most enriched terms using Gene Ontology (GO) classification. The pathways altered after SOX2 down-modulation includes multiple cellular processes such as amino-acid metabolism and intercellular signaling cascades. We also defined and classified the set of non coding transcripts differentially expressed regulated by SOX2 in GSCs, and validated two of them. CONCLUSIONS: We present a comprehensive analysis of the transcriptome controlled by SOX2 in GSCs, gaining insights in the understanding of the potential roles of SOX2 in glioblastoma. PMID- 27669422 TI - Exclusive concurrent radiochemotherapy for advanced head and neck cancers with 'fractionated' 5-fluorouracil and cisplatin. AB - Concurrent radiochemotherapy (CRC) is a standard treatment in patients with inoperable locoregionally advanced ear-nose-throat (ENT) cancer. We report the safety and efficacy of CRC with daily fractionated 5-fluorouracil and cisplatin ('F' 5FU-CDDP) in a monocentric retrospective cohort. From January 2006 to August 2012, all patients with unresectable (or inoperable) nonmetastatic locoregionally advanced ENT cancer treated curatively by means of radiotherapy (normal fractionated 70 Gy to the macroscopic tumor and prophylactic 50 Gy) with three courses (week 1-week 4-week 7) of 'F' 5FU-CDDP regimen (800 mg/m/day of 5 fluorouracil and 20 mg/m/day of CDDP from day 1 to day 4) were included. Seventy patients underwent CRC (86% men, median age 58 years old, 100% squamous cell carcinoma, 97% stage III/IV). Fifty-six patients received the three complete courses of chemotherapy with cumulative doses of CDDP of 217 mg/m/patient (dose intensity ratio of 90.5%). After a median follow-up period of 30.7 months, median overall and disease-free survivals were 34.1 [95% confidence interval (CI) (21.6 56.8)] and 50.2 months [95% CI (17.4-NA)] with 71% [95% CI (57.5-81)] and 67% [95% CI (51.8-78.5)] for locoregional control at 2 and 5 years, respectively. In all, 58.5% of grade 3 or higher mucositis and 24% of radioepithelitis were observed, but only 11.5, 3, and 1.5% of grade 3 or higher neutropenia, nephrotoxicity, and neurotoxicity were observed, respectively. No deaths from toxicity occurred. CRC with three courses of 'F' 5FU-CDDP appears effective and could be an alternative to standard CRC treatment. Randomized studies are required to be able to use this treatment regimen routinely. PMID- 27669424 TI - A contemporary decennial examination of changing agricultural field sizes using Landsat time series data. AB - Field size distributions and their changes have not been studied over large areas as field size change datasets are not available. This study quantifies agricultural field size changes in a consistent manner using Landsat satellite data that also provide geographic context for the observed decadal scale changes. Growing season cloud-free Landsat 30 m resolution images acquired from 9 to 25 years apart were used to extract field object classifications at seven sites located by examination of a global agricultural yield map, agricultural production statistics, literature review, and analysis of the imagery in the US Landsat archive. High spatial resolution data were used to illustrate issues identifying small fields that are not reliably discernible at 30 m Landsat resolution. The predominant driver of field size change was attributed by literature review. Significant field size changes were driven by different factors, including technological advancements (Argentina and USA), government land use and agricultural policies (Malaysia, Brazil, France), and political changes (Albania and Zimbabwe). While observed local field size changes were complex, the reported results suggest that median field sizes are increasing due to technological advancements and changes to government policy, but may decrease where abrupt political changes affect the agricultural sector and where pastures are converted to arable land uses. In the limited sample considered, median field sizes increased from 45% (France) to 159% (Argentina) and decreased from 47% (Brazil) to 86% (Albania). These changes imply significant impacts on landscape spatial configuration and land use diversity with ecological and biogeochemical consequences. PMID- 27669423 TI - Docetaxel and mitoxantrone before radical prostatectomy in men with high-risk prostate cancer: 10-year follow-up and immune correlates. AB - The aims of this study were to report the clinical outcomes in a cohort of men with high-risk prostate cancer treated with neoadjuvant docetaxel and mitoxantrone 10 years after treatment, identify pretreatment clinical parameters that may be predictors of recurrence, and describe tumor-infiltrating leukocytes present in radical prostatectomy specimens. We conducted a phase I/II study of neoadjuvant docetaxel and mitoxantrone before radical prostatectomy in high-risk localized prostate cancer to determine the feasibility of this combination and predictors of prostate cancer recurrence after cytotoxic chemotherapy. After 10 years of follow-up, 34 (63%) of 54 participants experience a recurrence. In univariate analysis, prostate-specific antigen (PSA) density (P=0.01), pathological stage (P=0.03), lymph node status (P<0.0001), seminal vesicle invasion (P=0.003), and tissue vascular endothelial growth factor (VEGF) expression (P=0.016) were significantly associated with recurrence. In multivariate analysis, only lymph node status, PSA density, and VEGF expression were significant predictors of disease recurrence. We used a tissue microarray for the first 50 participants to characterize the tumor-infiltrating lymphocytes and evaluate them for association with recurrence. We measured CD3, CD4, CD8, FoxP3, CD20, CD15, CD68, and CD163 by immunohistochemistry in both tumor and normal prostate specimens, but did not find an association between immunophenotype and recurrence. There was a significantly different density of CD68 and CD163 cells between normal and tumor tissue. Lymph node status, PSA density, and tissue VEGF expression predict recurrence after chemotherapy for high-risk prostate cancer. Additional studies are needed to determine the potential benefit of chemotherapy in the neoadjuvant setting. PMID- 27669426 TI - The Impact of Race on Patient Satisfaction With Primary Care Physicians. AB - Patient satisfaction has become an important measure of health care services and outcomes. The purpose of this empirical study was to investigate factors that impact the satisfaction of primary care physicians (PCPs) by patients of different races in the United States. This is an empirical analysis of the Center for Studying Health System Change's 2010 Health Tracking Household Survey. Correlation and regression analyses were done to examine the impact of various factors on PCP satisfaction of 12 472 American respondents. Whites were most satisfied with their PCPs, and Hispanics were least satisfied with their PCPs. Satisfaction with health care received in the last 12 months and the need to defer medical treatment due to financial issues had a significant impact on patients' satisfaction with PCPs across all races. General health status significantly impacted satisfaction with PCPs for African American and Hispanic respondents. Satisfaction with PCPs significantly varied among different races based on the type of their health insurance. Education negatively impacted PCP satisfaction of white and non-Hispanic respondents. Satisfaction with PCPs varies based on the race of patients. It can be impacted by a number of factors outside the control of the physician such as the general health of patients, type of insurance, and patients' need to defer medical treatment due to financial issues. The use of patient satisfaction surveys by health care administrators to measure organizational outcomes may have limited validity. PMID- 27669428 TI - A Trend Analysis of Succession Planning in Health Care as Perceived by Chief Executive Officers in US Hospitals. AB - A study was conducted to analyze the perceptions of chief executive officers in US hospitals regarding leadership development and succession planning. Results of the study were compared to identical surveys delivered in previous years for the purposes of identifying possible trends and changing perspectives related to how executives use succession planning in their facilities, what factors influence the identification of successors, what positions are the more likely to use succession planning efforts, and who specifically should be responsible for building the leadership pipeline. PMID- 27669427 TI - Consumer Health Informatics: Promoting Patient Self-care Management of Illnesses and Health. AB - Consumer health informatics (CHI) is propelling important changes for medical providers and the lives of patients through information and communications technology. Independently, medical consumers seek, collect, and use health information for decision making. However, when constructing a CHI-based medical platform, high technology must be applied in a fully understandable and usable format for both health care providers and consumers. This study examines the present status of CHI and its effect on medical consumers. For the development of CHI, we discuss the need for tailored health communications and capacity building with chronic patients at the medical center. First, empowerment is a key characteristic needed for medical consumer health care management. However, promoting patient self-care management of illnesses and health is necessary to create conjugation where cooperation with medical service providers is possible. Also, establishing a health care delivery system that will support cooperation is necessary. Second, tailored health communications can uniquely construct the health information of patients, which prevents unnecessary or excessive information from leading patients to confused and inappropriate decisions. Ultimately, through the present environment of health communication, the innovation of a consumer health care information system has become the tide of the times and the positive effect of improved health can be expected. PMID- 27669425 TI - Characteristics of Pos19 - A Small Coding RNA in the Oxidative Stress Response of Rhodobacter sphaeroides. AB - The phototrophic bacterium Rhodobacter sphaeroides induces several small RNAs (sRNAs) when singlet oxygen (1O2) levels are elevated, a situation also referred to as photo-oxidative stress. An RNA-seq study identified the RSs0019 sRNA, which is renamed Pos19 (photo-oxidative stress induced sRNA 19). Pos19 is part of the RpoE regulon and consequently induced upon 1O2 and peroxide stress. The 219 nt long Pos19 transcript contains a small open reading frame (sORF) of 150 nt, which is translated in vivo. Over-expression of Pos19 results in reduced mRNA levels for several genes, of which numerous are involved in sulfur metabolism. The negative effect on the potential targets is maintained even when translation of the sORF is abolished, arguing that regulation is entailed by the sRNA itself. Reporter studies further revealed that regulation of the most affected mRNA, namely RSP_0557, by Pos19 is Hfq-dependent. Direct binding of Pos19 to Hfq was shown by co-immunoprecipitation. Physiological experiments indicated Pos19 to be involved in the balance of glutathione biosynthesis. Moreover, a lack of Pos19 leads to elevated reactive oxygen species levels. Taken together our data identify the sRNA Pos19 as a coding sRNA with a distinct expression pattern and potential role under oxidative stress in the phototrophic bacterium R. sphaeroides. PMID- 27669429 TI - Using Organizational Development for Electronic Medical Record Transformation. AB - With mandates requiring the transition from paper medical records to the use of electronic medical records, organizations are embarking on a change process. To engender this process, organizational development models and interventions based predominantly on the theories of Chris Argyris, Warren Bennis, and the team of Paul Lawrence and Jay Lorsch are explored. Interventions are subdivided into behavioral and structural as organizations benefit by recognizing a need for change and, perhaps, a cultural shift in addition to refocusing their mission. To support these interventions, a champion or super user is recommended to maintain the momentum of the transformation and enculturation. With so many changes in the internal and external environments, organizations must respond systematically for, in health care, lives depend on it. PMID- 27669430 TI - Identification of Genes Potentially Associated with the Fertility Instability of S-Type Cytoplasmic Male Sterility in Maize via Bulked Segregant RNA-Seq. AB - S-type cytoplasmic male sterility (CMS-S) is the largest group among the three major types of CMS in maize. CMS-S exhibits fertility instability as a partial fertility restoration in a specific nuclear genetic background, which impedes its commercial application in hybrid breeding programs. The fertility instability phenomenon of CMS-S is controlled by several minor quantitative trait locus (QTLs), but not the major nuclear fertility restorer (Rf3). However, the gene mapping of these minor QTLs and the molecular mechanism of the genetic modifications are still unclear. Using completely sterile and partially rescued plants of fertility instable line (FIL)-B, we performed bulk segregant RNA-Seq and identified six potential associated genes in minor effect QTLs contributing to fertility instability. Analyses demonstrate that these potential associated genes may be involved in biological processes, such as floral organ differentiation and development regulation, energy metabolism and carbohydrates biosynthesis, which results in a partial anther exsertion and pollen fertility restoration in the partially rescued plants. The single nucleotide polymorphisms (SNPs) identified in two potential associated genes were validated to be related to the fertility restoration phenotype by KASP marker assays. This novel knowledge contributes to the understanding of the molecular mechanism of the partial fertility restoration of CMS-S in maize and thus helps to guide the breeding programs. PMID- 27669431 TI - The Role of Chronic Psychosocial Stress in Explaining Racial Differences in Stress Reactivity and Pain Sensitivity. AB - OBJECTIVE: To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. METHODS: Participants included 133 AA and non-Hispanic white (nHW) individuals (mean [SD] age, 37 [9]) matched for age, sex, and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. RESULTS: Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g., r = -.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. CONCLUSIONS: Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs' increased pain sensitivity in laboratory settings. PMID- 27669432 TI - Cell cycle-coupled expansion of AR activity promotes cancer progression. AB - The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention. PMID- 27669433 TI - Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis. AB - The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor progression and metastasis through distinct tumor cell-intrinsic and -extrinsic mechanisms, and may represent a novel and therapeutically viable approach for treating metastatic cancers. PMID- 27669434 TI - Targeting KRas-dependent tumour growth, circulating tumour cells and metastasis in vivo by clinically significant miR-193a-3p. AB - KRas is mutated in a significant number of human cancers and so there is an urgent therapeutic need to target KRas signalling. To target KRas in lung cancers we used a systems approach of integrating a genome-wide miRNA screen with patient derived phospho-proteomic signatures of the KRas downstream pathway, and identified miR-193a-3p, which directly targets KRas. Unique aspects of miR-193a 3p biology include two functionally independent target sites in the KRas 3'UTR and clinically significant correlation between miR-193a-3p and KRas expression in patients. Rescue experiments with mutated KRas 3'UTR showed very significantly that the anti-tumour effect of miR-193a-3p is via specific direct targeting of KRas and not due to other targets. Ex vivo and in vivo studies utilizing nanoliposome packaged miR-193a-3p demonstrated significant inhibition of tumour growth, circulating tumour cell viability and decreased metastasis. These studies show the broader applicability of using miR-193a-3p as a therapeutic agent to target KRas-mutant cancer. PMID- 27669435 TI - The interaction between acetylation and serine-574 phosphorylation regulates the apoptotic function of FOXO3. AB - The multispecific transcription factor and tumor suppressor FOXO3 is an important mediator of apoptosis, but the mechanisms that control its proapoptotic function are poorly understood. There has long been evidence that acetylation promotes FOXO3-driven apoptosis and recently a specific JNK (c-Jun N-terminal kinase) dependent S574 phosphorylated form (p-FOXO3) has been shown to be specifically apoptotic. This study examined whether acetylation and S574 phosphorylation act independently or in concert to regulate the apoptotic function of FOXO3. We observed that both sirtuins 1 and 7 (SIRT1 and SIRT7) are able to deacetylate FOXO3 in vitro and in vivo, and that lipopolysaccharide (LPS) treatment of THP-1 monocytes induced a rapid increase of FOXO3 acetylation, partly by suppression of SIRT1 and SIRT7. Acetylation was required for S574 phosphorylation and cellular apoptosis. Deacetylation of FOXO3 by SIRT activation or SIRT1 or SIRT7 overexpression prevented its S574 phosphorylation and blocked apoptosis in response to LPS. We also found that acetylated FOXO3 preferentially bound JNK1, and a mutant FOXO3 lacking four known acetylation sites (K242, 259, 290 and 569R) abolished JNK1 binding and failed to induce apoptosis. This interplay of acetylation and phosphorylation also regulated cell death in primary human peripheral blood monocytes (PBMs). PBMs isolated from alcoholic hepatitis patients had high expression of SIRT1 and SIRT7 and failed to induce p-FOXO3 and apoptosis in response to LPS. PBMs from healthy controls had lower SIRT1 and SIRT7 and readily formed p-FOXO3 and underwent apoptosis when similarly treated. These results reveal that acetylation is permissive for generation of the apoptotic form of FOXO3 and the activity of SIRT1 and particularly SIRT7 regulate this process in vivo, allowing control of monocyte apoptosis in response to LPS. PMID- 27669436 TI - Downregulation of CXCL12 in mesenchymal stromal cells by TGFbeta promotes breast cancer metastasis. AB - Mesenchymal stromal cells (MSCs) are one of major components of the tumour microenvironment. Recent studies have shown that MSC tumour residence and their close interactions with inflammatory factors are important factors that affect tumour progression. Among tumour-associated inflammatory factors, transforming growth factor beta (TGFbeta) is regarded as a key determinant of malignancy. By employing a lung metastasis model of a murine breast cancer, we show here that the prometastatic effect of MSCs was dependent on their response to TGFbeta. Interestingly, we found that MSC-produced CXCL12, an important chemokine in tumour metastasis, was markedly inhibited by TGFbeta. Furthermore, silencing of CXCL12 in TGFbeta-unresponsive MSCs restored their ability to promote tumour metastasis. We found that 4T1 breast cancer cells expressed high levels of CXCR7, but not of CXCR4, both of which are CXCL12 receptors. In presence of CXCL12, CXCR7 expression on tumour cells was decreased. Indeed, when CXCR7 was silenced in breast cancer cells, their metastatic ability was inhibited. Therefore, our data demonstrated that sustained expression of CXCL12 by MSCs in the primary tumour site inhibits metastasis through reduction of CXCR7, while, in the presence of TGFbeta, this CXCL12 effect of MSCs on tumour cells is relieved. Importantly, elevated CXCR7 and depressed CXCL12 expression levels were prominent features of clinical breast cancer lesions and were related significantly with poor survival. Our findings reveal a novel mechanism of MSC effects on malignant cells through which crosstalk between MSCs and TGFbeta regulates tumour metastasis. PMID- 27669437 TI - The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion. AB - DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest similarity to DOCK1, remains sparingly studied. Here we establish that DOCK5 has a non-redundant role in regulating motile and invasive capacities of epithelial cells. DOCK1 is constitutively associated with sites of integrin attachment termed focal adhesions (FAs). In contrast, we demonstrate that DOCK5 recruitment to FAs in Hela cells is restricted by GIT2, an established regulator of FA signaling. We determine that GIT2 is targeted to FAs in response to Rho-ROCK signaling and actomyosin contractility. Accordingly, inhibition of ROCK activity or MLC function promotes enrichment of DOCK5 in membrane protrusions and nascent cell substratum adhesions. We further demonstrate that GIT2 inhibits the interaction of DOCK5 with Crk. Moreover, we show that depletion of GIT2 promotes DOCK5 dependent activation of the Crk-p130Cas signaling cascade to promote Rac1 mediated lamellipodial protrusion and FA turnover. The antagonism between GIT2 and DOCK5 extends to non-transformed MCF10A mammary epithelial cells, with DOCK5 'dialing-up' and GIT2 'dialing-down' invasiveness. Finally, we determine that DOCK5 inhibition attenuates invasion and metastasis of MDA-MB-231 cells and prolongs life span of mice injected with these cells. Collectively, our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases. PMID- 27669438 TI - CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients. AB - The CXCR4 receptor and its ligand CXCL12 (also named stromal cell-derived factor 1, SDF1) have a critical role in chemotaxis and homing, key steps in cancer metastasis. Although myofibroblasts expressing CXCL12 are associated with the presence of axillary metastases in HER2 breast cancers (BC), the therapeutic interest of targeting CXCR4/CXCL12 axis in the different BC subtypes remains unclear. Here, we investigate this question by testing antitumor activity of CXCR4 inhibitors in patient-derived xenografts (PDX), which faithfully reproduce human tumor properties. We observed that two CXCR4 inhibitors, AMD3100 and TN14003, efficiently impair tumor growth and metastasis dissemination in both Herceptin-sensitive and Herceptin-resistant HER2 BC. Conversely, blocking CXCR4/CXCL12 pathway in triple-negative (TN) BC does not reduce tumor growth, and can even increase metastatic spread. Moreover, although CXCR4 inhibitors significantly reduce myofibroblast content in all BC subtypes, they decrease angiogenesis only in HER2 BC. Thus, our findings suggest that targeting CXCR4 could provide some therapeutic interest for HER2 BC patients, whereas it has no impact or could even be detrimental for TN BC patients. PMID- 27669439 TI - The MACC1-SPON2 axis: a new biomarker and therapeutic target in colorectal cancer. AB - In this issue of the Journal, Schmid et al identify Spondin 2 (SPON2) as a prominent downstream signaling target of metastasis-associated in colon cancer 1 (MACC1) in colorectal cancer (CRC). It is shown that SPON2 mediates MACC1-induced CRC cell proliferation, invasion and metastasis in vitro and in vivo, while its high expression correlates with adverse disease free survival in clinical samples. Therefore, not only does this study shed further light into the complexity of colorectal carcinogenesis, but it also puts forward a potential novel prognostic biomarker to predict high-risk tumors before they metastasize. The MACC1/SPON2 axis may also have utility beyond an indicator of tumor aggressiveness and lends itself as a promising therapeutic target for colorectal and potentially other solid tumors. PMID- 27669442 TI - Arterial Stiffness Is Reduced Regardless of Resistance Training Load in Young Men. AB - PURPOSE: Discrepancies regarding the effect of resistance exercise training (RET) on arterial stiffness have led to uncertainty regarding the effect of RET on cardiovascular health. Confounding our understanding in this area are the roles of the following: load (heavier vs lighter), participant cardiovascular health, and arterial stiffness assessment method. We aimed to investigate the effects of a heavier versus a lighter load resistance training protocol on both central and local arterial stiffness in previously trained young men. METHODS: Participants were randomly assigned to a 12-wk supervised whole-body RET program consisting of three sets of 8-12 repetitions (heavier-load, lower-repetition [LR]; n = 16) or three sets of 20-25 repetitions (lighter-load, higher-repetition [HR]; n = 16) to volitional failure, or a control group who maintained their regular activity habits (n = 14). Central arterial stiffness (carotid-femoral pulse wave velocity), local arterial stiffness (common carotid arterial distensibility), and left ventricular mass were measured before and after 12 wk of RET. RESULTS: There was a reduction in carotid-femoral pulse wave velocity in both LR (6.24 +/- 0.56 vs 5.77 +/- 0.76 m.s; P < 0.05) and HR (6.42 +/- 0.70 vs 5.72 +/- 0.60 m.s; P < 0.05) with no changes in carotid distensibility (P = 0.52) or left ventricular mass allometrically scaled to fat-free mass (P = 0.60). There were no changes in any variable in the control group. CONCLUSIONS: Using current criterion-standard assessment methods, central arterial stiffness was reduced after resistance training, regardless of the load lifted during RET, with no effect on local carotid artery distensibility or left ventricular mass. Our results support a role of RET in the promotion of positive adaptations in vascular function. PMID- 27669440 TI - From identification of the BTK kinase to effective management of leukemia. AB - BTK is a cytoplasmic protein-tyrosine kinase, whose corresponding gene was isolated in the early 1990s. BTK was initially identified by positional cloning of the gene causing X-linked agammaglobulinemia and independently in a search for new kinases. Given the phenotype of affected patients, namely lack of B lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody mediated pathologies, such as autoimmunity. In contrast to, for example, the SRC family of cytoplasmic kinases, there was no obvious way in which structural alterations would yield constitutively active forms of BTK, and such mutations were also not found in leukemias or lymphomas. In 2007, the first efficient inhibitor, ibrutinib, was reported and soon became approved both in the United States and in Europe for the treatment of three B-cell malignancies, mantle cell lymphoma, chronic lymphocytic leukemia and Waldenstrom's macroglobulinemia. Over the past few years, additional inhibitors have been developed, with acalabrutinib being more selective, and recently demonstrating fewer clinical adverse effects. The antitumor mechanism is also not related to mutations in BTK. Instead tumor residency in lymphoid organs is inhibited, making these drugs highly versatile. BTK is one of the only 10 human kinases that carry a cysteine in the adenosine triphosphate-binding cleft. As this allows for covalent, irreversible inhibitor binding, it provides these compounds with a highly advantageous character. This quality may be crucial and bodes well for the future of BTK-modifying medicines, which have been estimated to reach annual multi-billion dollar sales in the future. PMID- 27669443 TI - Spinal Cord Injury Level Influences Acute Plasma Caffeine Responses. AB - PURPOSE: This study aimed to investigate the absorption curve and acute effects of caffeine at rest in individuals with no spinal cord injury (SCI), paraplegia (PARA), and tetraplegia (TETRA). METHODS: Twenty-four healthy males (eight able bodied [AB], eight PARA, and eight TETRA) consumed 3 mg.kg caffeine anhydrous (CAF) in a fasted state. Plasma caffeine [CAF], glucose, lactate, free fatty acid, and catecholamine concentrations were measured during a 150-min rest period. RESULTS: Peak [CAF] was greater in TETRA (21.5 MUM) compared with AB (12.2 MUM) and PARA (15.1 MUM), and mean peak [CAF] occurred at 70, 80, and 80 min, respectively. Moderate and large effect sizes were revealed for TETRA compared with PARA and AB (-0.55 and -1.14, respectively) for the total area under the [CAF] versus time curve. Large interindividual responses were apparent in SCI groups. The change in plasma catecholamine concentrations after CAF did not reach significance (P > 0.05); however, both adrenaline and noradrenaline concentrations were lowest in TETRA. Significant increases in free fatty acid were seen over time (P < 0.0005), but there was no significant influence of SCI level. Blood lactate concentration reduced over time (P = 0.022), whereas blood glucose concentration decreased modestly (P = 0.695), and no difference between groups was seen (P > 0.05). CONCLUSION: The level of SCI influenced the caffeine absorption curve, and there was large interindividual variation within and between groups. Individual curves should be considered when using caffeine as an ergogenic aid in athletes with an SCI. The results indicate TETRA should trial low doses in training and PARA may consider consuming caffeine greater than 60 min before exercise performance. The study also supports caffeine's direct effect on adipose tissue, which is not secondary to catecholamine release. PMID- 27669441 TI - Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. AB - Cancer-associated fibroblasts (CAFs) comprise the majority of the tumor bulk of pancreatic ductal adenocarcinomas (PDACs). Current efforts to eradicate these tumors focus predominantly on targeting the proliferation of rapidly growing cancer epithelial cells. We know that this is largely ineffective with resistance arising in most tumors following exposure to chemotherapy. Despite the long standing recognition of the prominence of CAFs in PDAC, the effect of chemotherapy on CAFs and how they may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that CAFs exposed to chemotherapy have an active role in regulating the survival and proliferation of cancer cells. We found that CAFs are intrinsically resistant to gemcitabine, the chemotherapeutic standard of care for PDAC. Further, CAFs exposed to gemcitabine significantly increase the release of extracellular vesicles called exosomes. These exosomes increased chemoresistance-inducing factor, Snail, in recipient epithelial cells and promote proliferation and drug resistance. Finally, treatment of gemcitabine-exposed CAFs with an inhibitor of exosome release, GW4869, significantly reduces survival in co-cultured epithelial cells, signifying an important role of CAF exosomes in chemotherapeutic drug resistance. Collectively, these findings show the potential for exosome inhibitors as treatment options alongside chemotherapy for overcoming PDAC chemoresistance. PMID- 27669445 TI - Triathletes Lose Their Advantageous Pain Modulation under Acute Psychosocial Stress. AB - INTRODUCTION: Triathletes, who constantly engage in intensely stressful sport, were recently found to exhibit greater pain tolerance and more efficient pain inhibition capabilities than nonathletes. However, pain inhibition correlated negatively with retrospective reports of mental stress during training and competition. The aim of the current study was to test pain inhibition capabilities of triathletes under acute, controlled psychological stress manipulation. METHODS: Participants were 25 triathletes and ironman triathletes who underwent the measurement of pain threshold, pain intolerance, tonic suprathreshold pain, and conditioned pain modulation before and during exposure to the Montreal Imaging Stress Task (MIST). Perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol levels were obtained as indices of stress. RESULTS: The MIST induced a significant stress reaction manifested in the subjective and objective indices. Overall, a significant reduction in pain threshold and in conditioned pain modulation efficacy was observed after the MIST, which reached the baseline levels observed previously in nonathletes. Paradoxically, the magnitude of this stress-induced hyperalgesia (SIH) correlated negatively with the magnitude of the stress response; low-stress responders exhibited greater SIH than high-stress responders. CONCLUSION: The results suggest that under acute psychological stress, triathletes not only react with SIH and a reduction in pain modulation but also lose their advantageous pain modulation over nonathletes. The stronger the stress response recorded, the weaker the SIH. It appears that triathletes are not resilient to stress, responding with an increase in the sensitivity to pain as well as a decrease in pain inhibition. The possible effects of athletes' baseline pain profile and stress reactivity on SIH are discussed. PMID- 27669444 TI - The Effect of a Healthy Lifestyle on Future Physical Functioning in Midlife Women. AB - PURPOSE: This study aimed to examine the prospective association between healthy lifestyle behaviors and objectively measured physical function in midlife women. METHODS: Participants included 1769 racially/ethnically diverse women, ages 56-68 yr, from the Study of Women's Health Across the Nation cohort. Physical function was assessed at the 13th follow-up visit with the Short Physical Performance Battery (4-m walk, repeated chair stands, and balance test) and grip strength. A healthy lifestyle score (HLS), which ranged from 0 to 6, was calculated by averaging as many as three repeated measures of self-reported smoking, physical activity, and diet, all assessed before the 13th follow-up. Multivariable linear and logistic regressions modeled each component of physical performance as a function of HLS and, in separate models, of each lifestyle behavior, adjusted for the other behaviors. RESULTS: In multivariable analyses, the time for the 4-m walk was 0.06 s faster (P = 0.001) for every 1 point increase in the HLS. The time for the repeated chair stands was significantly shorter by approximately 0.20 s. Neither grip strength nor balance problems were significantly associated with the HLS (P = 0.28 and P = 0.19, respectively). The model examining the individual health behaviors showed that only physical activity was significantly associated with physical performance. CONCLUSION: Regular physical activity in early midlife has the potential to reduce the likelihood of physical functional limitations later in midlife. PMID- 27669447 TI - High-Intensity Interval Training Increases Cardiac Output and VO2max. AB - : Increases in maximal oxygen uptake (VO2max) frequently occur with high intensity interval training (HIIT), yet the specific adaptation explaining this result remains elusive. PURPOSE: This study examined changes in VO2max and cardiac output (CO) in response to periodized HIIT. METHODS: Thirty-nine active men and women (mean age and VO2max = 22.9 +/- 5.4 yr and 39.6 +/- 5.6 mL.kg.min) performed HIIT and 32 men and women (age and VO2max = 25.7 +/- 4.5 yr and 40.7 +/ 5.2 mL.kg.min) were nonexercising controls (CON). The first 10 sessions of HIIT required eight to ten 60 s bouts of cycling at 90%-110% percent peak power output interspersed with 75 s recovery, followed by randomization to one of three regimes (sprint interval training (SIT), high-volume interval training (HIITHI), or periodized interval training (PER) for the subsequent 10 sessions. Before, midway, and at the end of training, progressive cycling to exhaustion was completed during which VO2max and maximal CO were estimated. RESULTS: Compared with CON, significant (P < 0.001) increases in VO2max in HIIT + SIT (39.8 +/- 7.3 mL.kg.min to 43.6 +/- 6.1 mL.kg.min), HIIT + HIITHI (41.1 +/- 4.9 mL.kg.min to 44.6 +/- 7.0 mL.kg.min), and HIIT + PER (39.5 +/- 5.6 mL.kg.min to 44.1 +/- 5.4 mL.kg.min) occurred which were mediated by significant increases in maximal CO (20.0 +/- 3.1 L.min to 21.7 +/- 3.2 L.min, P = 0.04). Maximal stroke volume was increased with HIIT (P = 0.04), although there was no change in maximal HR (P = 0.88) or arteriovenous O2 difference (P = 0.36). These CO data are accurate and represent the mean changes from pre- to post-HIIT across all three training groups. CONCLUSIONS: Increases in VO2max exhibited in response to different HIIT regimes are due to improvements in oxygen delivery. PMID- 27669446 TI - Metabolic Responses to the Yukon Arctic Ultra: Longest and Coldest in the World. AB - PURPOSE: The Yukon Arctic Ultra is considered the longest and coldest ultraendurance event in the world. Cold exposure and exercise has been reported to influence circulating levels of myokines, adipokines, and hepatokines that may influence considerable alterations in the regulation of metabolism. The purpose of the study was to evaluate the influence of the Yukon Arctic Ultra (430-mile event) on potential activators of brown fat, metabolites, and body composition in healthy individuals. METHODS: Eight male and female participants (mean +/- SEM: age, 44 +/- 3 yr; body mass index, 23.4 +/- 0.9) were recruited for participation. Blood samples were collected at pre-event, mid-event, and post event checkpoints. RESULTS: The temperature during the event ranged from -45 degrees C to -8 degrees C. Because of these extremely challenging conditions, 50% of the participants withdrew from competition by the 300-mile mark, and those that surpassed 300 miles lost a significant (P = 0.002; P = 0.01) amount of body weight (76 +/- 5 kg to 73 +/- 4 kg) and fat mass (13 +/- 1 kg to 12 +/- 3 kg), respectively. With respect to serum irisin, there was a trend (P = 0.06) toward significance from pre-event (1033 +/- 88 ng.mL), mid-event (1265 +/- 23 ng.mL) to post-event (1289 +/- 24 ng.mL). Serum meteorin-like and fibroblast growth factor 21 remained stable throughout the event. There were no changes in creatinine, acetoacetate, acetate, and valine. Serum lactate decreased (P = 0.04) during the event. CONCLUSIONS: The influence of cold exposure and extreme physical exertion may promote substantial increases in serum irisin, and specific alterations in substrate metabolism that largely preserve skeletal muscle and physiological resilience. PMID- 27669448 TI - Knee Joint Loading during Single-Leg Forward Hopping. AB - : Increased or abnormal loading on the intact limb is thought to contribute to the relatively high risk of knee osteoarthritis in this limb for individuals with unilateral lower limb loss. This theory has been assessed previously by studying walking, but knee joint loading during walking is often similar between individuals with and without limb loss, prompting assessment of other movements that may place unusual loads on the knee. One such movement, hopping, is a form of locomotion that individuals with unilateral lower limb loss may situationally use instead of walking, but the mechanical effects of hopping on the intact limb are unknown. PURPOSE: Compare knee joint kinetics of healthy adults during single leg forward hopping compared to walking, a more traditional form of locomotion. METHODS: Twenty-four healthy adults walked and hopped at self-selected speeds of 1.5 and 2.3 m.s, respectively. Joint moments were calculated using inverse dynamics. A paired Student's t-test was utilized to compare peak, impulse, and loading rate (LR) of knee adduction moment (KAM), and peak knee flexion moment (KFM) between walking and hopping. RESULTS: Peak KFM and KAM LR were greater during hopping compared to walking (peak KFM: 20.73% vs 5.51% body weight (BW) * height (Ht), P < 0.001; KAM LR: 0.47 vs. 0.33 BW.Ht.s, P = 0.01). CONCLUSIONS: Kinetic measures affecting knee joint loading are greater in hopping compared to walking. It may be advisable to limit single-leg forward hopping in the limb loss population until it is known if these loads increase knee osteoarthritis risk. PMID- 27669449 TI - Voluntary Running Attenuates Metabolic Dysfunction in Ovariectomized Low-Fit Rats. AB - INTRODUCTION: Ovariectomy and high-fat diet (HFD) worsen obesity and metabolic dysfunction associated with low aerobic fitness. Exercise training mitigates metabolic abnormalities induced by low aerobic fitness, but whether the protective effect is maintained after ovariectomy and HFD is unknown. PURPOSE: This study determined whether, after ovariectomy and HFD, exercise training improves metabolic function in rats bred for low intrinsic aerobic capacity. METHODS: Female rats selectively bred for low (LCR) and high (HCR) intrinsic aerobic capacity (n = 30) were ovariectomized, fed HFD, and randomized to either a sedentary (SED) or voluntary wheel running (EX) group. Resting energy expenditure, glucose tolerance, and spontaneous physical activity were determined midway through the experiment, whereas body weight, wheel running volume, and food intake were assessed throughout the study. Body composition, circulating metabolic markers, and skeletal muscle gene and protein expression were measured at sacrifice. RESULTS: EX reduced body weight and adiposity in LCR rats (-10% and -50%, respectively; P < 0.05) and, unexpectedly, increased these variables in HCR rats (+7% and +37%, respectively; P < 0.05) compared with their respective SED controls, likely because of dietary overcompensation. Wheel running volume was approximately fivefold greater in HCR than LCR rats, yet EX enhanced insulin sensitivity equally in LCR and HCR rats (P < 0.05). This EX-mediated improvement in metabolic function was associated with thee gene upregulation of skeletal muscle interleukin-6 and interleukin-10. EX also increased resting energy expenditure, skeletal muscle mitochondrial content (oxidative phosphorylation complexes and citrate synthase activity), and adenosine monophosphate-activated protein kinase activation similarly in both lines (all P <0.05). CONCLUSION: Despite a fivefold difference in running volume between rat lines, EX similarly improved systemic insulin sensitivity, resting energy expenditure, and skeletal muscle mitochondrial content and adenosine monophosphate-activated protein kinase activation in ovariectomized LCR and HCR rats fed HFD compared with their respective SED controls. PMID- 27669450 TI - Step-Based Physical Activity Metrics and Cardiometabolic Risk: NHANES 2005-2006. AB - PURPOSE: This study aimed to catalog the relationships between step-based accelerometer metrics indicative of physical activity volume (steps per day, adjusted to a pedometer scale), intensity (mean steps per minute from the highest, not necessarily consecutive, minutes in a day; peak 30-min cadence), and sedentary behavior (percent time at zero cadence relative to wear time; %TZC) and cardiometabolic risk factors. METHODS: We analyzed data from 3388 participants, 20+ yr old, in the 2005-2006 National Health and Nutrition Examination Survey with >=1 valid day of accelerometer data and at least some data on weight, body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, HDL cholesterol, triglycerides, and/or glycohemoglobin. Linear trends were evaluated for cardiometabolic variables, adjusted for age and race, across quintiles of steps per day, peak 30-min cadence, and %TZC. RESULTS: Median steps per day ranged from 2247 to 12,334 steps per day for men and from 1755 to 9824 steps per day for women, and median peak 30-min cadence ranged from 48.1 to 96.0 steps per minute for men and from 40.8 to 96.2 steps per minute for women for the first and fifth quintiles, respectively. Linear trends were statistically significant (all P < 0.001), with increasing quintiles of steps per day and peak 30-min cadence inversely associated with waist circumference, weight, body mass index, and insulin for both men and women. Median %TZC ranged from 17.6% to 51.0% for men and from 19.9% to 47.6% for women for the first and fifth quintiles, respectively. Linear trends were statistically significant (all P < 0.05), with increasing quintiles of %TZC associated with increased waist circumference, weight and insulin for men, and insulin for women. CONCLUSIONS: This analysis identified strong linear relationships between step-based movement/nonmovement dimensions and cardiometabolic risk factors. These data offer a set of quantified access points for studying the potential dose-response effects of each of these dimensions separately or collectively in longitudinal observational or intervention study designs. PMID- 27669451 TI - Combined Exercise Training Improves Glycemic Control in Adult with Cystic Fibrosis. AB - PURPOSE: Glucose abnormality and diabetes are the most common comorbidities in cystic fibrosis (CF). Combined (aerobic and resistance) exercise program in type 2 patients with diabetes demonstrated an improvement of glycemic control. The aim of the study was to determine whether a combined exercise program is beneficial to improve plasma glucose at 2 h of the oral glucose tolerance test in CF. METHOD: Eighteen adults with CF with glucose abnormality were recruited (Clinicaltrial.gov: NTC02127957), and 17 were randomly assigned to a control or exercise group for 12 wk. VO2max, oral glucose tolerance test, muscular endurance and strength, and quality of life were measured pre- and postintervention. RESULTS: Fourteen participants completed the protocol. Patients in the exercise group improved significantly their 2-h plasma glucose values (-2.34 +/- 1.26 mmol.L, P < 0.007, confidence interval = 99.22%) and presented a reduction of 17.2% (P < 0.05) in total glucose excursion. No significant change for other parameters was observed. CONCLUSION: A combined exercise program improves glycemic control in CF. PMID- 27669452 TI - Combined Use of Morphological and Molecular Tools to Resolve Species Mis Identifications in the Bivalvia The Case of Glycymeris glycymeris and G. pilosa. AB - Morphological and molecular tools were combined to resolve the misidentification between Glycymeris glycymeris and Glycymeris pilosa from Atlantic and Mediterranean populations. The ambiguous literature on the taxonomic status of these species requires this confirmation as a baseline to studies on their ecology and sclerochronology. We used classical and landmark-based morphometric approaches and performed bivariate and multivariate analyses to test for shell character interactions at the individual and population level. Both approaches generated complementary information. The former showed the shell width to length ratio and the valve asymmetry to be the main discriminant characters between Atlantic and Mediterranean populations. Additionally, the external microsculpture of additional and finer secondary ribs in G. glycymeris discriminates it from G. pilosa. Likewise, landmark-based geometric morphometrics revealed a stronger opisthogyrate beak and prosodetic ligament in G. pilosa than G. glycymeris. Our Bayesian and maximum likelihood phylogenetic analyses based on COI and ITS2 genes identified that G. glycymeris and G. pilosa form two separate monophyletic clades with mean interspecific divergence of 11% and 0.9% for COI and ITS2, respectively. The congruent patterns of morphometric analysis together with mitochondrial and nuclear phylogenetic reconstructions indicated the separation of the two coexisting species. The intraspecific divergence occurred during the Eocene and accelerated during the late Pliocene and Pleistocene. Glycymeris pilosa showed a high level of genetic diversity, appearing as a more robust species whose tolerance of environmental conditions allowed its expansion throughout the Mediterranean. PMID- 27669453 TI - Root-hair endophyte stacking in finger millet creates a physicochemical barrier to trap the fungal pathogen Fusarium graminearum. AB - The ancient African crop, finger millet, has broad resistance to pathogens including the toxigenic fungus Fusarium graminearum. Here, we report the discovery of a novel plant defence mechanism resulting from an unusual symbiosis between finger millet and a root-inhabiting bacterial endophyte, M6 (Enterobacter sp.). Seed-coated M6 swarms towards root-invading Fusarium and is associated with the growth of root hairs, which then bend parallel to the root axis, subsequently forming biofilm-mediated microcolonies, resulting in a remarkable, multilayer root-hair endophyte stack (RHESt). The RHESt results in a physical barrier that prevents entry and/or traps F. graminearum, which is then killed. M6 thus creates its own specialized killing microhabitat. Tn5-mutagenesis shows that M6 killing requires c-di-GMP-dependent signalling, diverse fungicides and resistance to a Fusarium-derived antibiotic. Further molecular evidence suggests long-term host endophyte-pathogen co-evolution. The end result of this remarkable symbiosis is reduced deoxynivalenol mycotoxin, potentially benefiting millions of subsistence farmers and livestock. Further results suggest that the anti-Fusarium activity of M6 may be transferable to maize and wheat. RHESt demonstrates the value of exploring ancient, orphan crop microbiomes. PMID- 27669454 TI - A Comparative Animal Study of Tendon Grafts Healing After Remnant-Preserving Versus Conventional Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND The aim of this study was to determine if anterior cruciate ligament (ACL) reconstruction by remnant preservation promotes cell proliferation, vascularization, proprioception recovery, and improved biomechanical properties of the tendon grafts. MATERIAL AND METHODS 75 New Zealand rabbits were randomly assigned into the control group (group A), conventional ACL reconstruction group (group B), ACL reconstruction using remnant preservation and graft through remnant sleeve technique group (group C), and ACL reconstruction using remnant preservation and remnant tensioning technique group (group D). The remnant and healing of tendon grafts in groups C and D were observed at 3, 6, and 12 weeks after surgery, and the mRNA expression levels of VEGF, NT-3 and GAP-43 in ACL (group A) or tendon graft samples (groups B, C, and D) were determined by real time PCR. Tendon graft cell count, microvessel density (MVD), and proprioceptors were determined by H&E staining, CD34, and S-100 immunohistochemical staining. The biomechanical properties of the tendon graft at week 12 in groups B, C, and D were examined by using a tensile strength test. RESULTS Remnant and tendon grafts were not healed at 3, 6, and 12 weeks after the operation in groups C and D. VEGF, NT-3, and GAP-43 mRNA expressions in groups B, C, and D were higher than those in group A (P<0.05), but no significant difference was observed between groups B, C, and D (P>0.05). Furthermore, tendon graft cell count, MVD, proprioception, and biomechanical properties showed no significant differences (P>0.05) among groups B, C, and D at various time points. CONCLUSIONS There was no significant difference in cell proliferation, vascularization, proprioception recovery, or biomechanical properties of the tendon grafts between remnant preserving and conventional ACL reconstruction methods. PMID- 27669455 TI - Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index. PMID- 27669456 TI - Addressing Social Determinants of Health and Health Inequalities. PMID- 27669458 TI - Effective approach to strengthen plasmon resonance localized on top surfaces of Ag nanoparticles and application in surface-enhanced Raman spectroscopy. AB - The spatial distribution of localized surface plasmon resonance (LSPR) plays a key role in many plasmonic applications. Based on the thermal stability of alumina templates, this work reports a novel approach to manipulate the distribution of LSPR and exhibits its significance for an important plasmonic application, the surface-enhanced Raman spectroscopy (SERS). A suitable thermal annealing sharpens the edges in top surfaces (far from the substrates) of Ag nanoparticles, which significantly strengthens the distal mode (DM) with the LSPR excited on the top surfaces. Because the top surface is the major place to adsorb probe molecules, this manipulation greatly improves the detection sensitivity of SERS. Our research provides a new way to improve the sensitivity of SERS, which also indicates that great care has to be taken on special LSPR mode which is largely responsible for a certain plasmonic application (e.g., the DM for SERS although it is not the major mode). PMID- 27669457 TI - Effect of Structured Physical Activity on Overall Burden and Transitions Between States of Major Mobility Disability in Older Persons: Secondary Analysis of a Randomized Trial. AB - Background: The total time a patient is disabled likely has a greater influence on his or her quality of life than the initial occurrence of disability alone. Objective: To compare the effect of a long-term, structured physical activity program with that of a health education intervention on the proportion of patient assessments indicating major mobility disability (MMD) (that is, MMD burden) and on the risk for transitions into and out of MMD. Design: Single-blinded, parallel group, randomized trial. (ClinicalTrials.gov: NCT01072500). Setting: 8 U.S. centers between February 2010 and December 2013. Participants: 1635 sedentary persons, aged 70 to 89 years, who had functional limitations but could walk 400 m. Intervention: Physical activity (n = 818) and health education (n = 817). Measurements: MMD, defined as the inability to walk 400 m, was assessed every 6 months for up to 3.5 years. Results: During a median follow-up of 2.7 years, the proportion of assessments showing MMD was substantially lower in the physical activity (0.13 [95% CI, 0.11 to 0.15]) than the health education (0.17 [CI, 0.15 to 0.19]) group, yielding a risk ratio of 0.75 (CI, 0.64 to 0.89). In a multistate model, the hazard ratios for comparisons of physical activity with health education were 0.87 (CI, 0.73 to 1.03) for the transition from no MMD to MMD; 0.52 (CI, 0.10 to 2.67) for no MMD to death; 1.33 (CI, 0.99 to 1.77) for MMD to no MMD; and 1.92 (CI, 1.15 to 3.20) for MMD to death. Limitation: The intention-to-treat principle was maintained for MMD burden and first transition out of no MMD, but not for subsequent transitions. Conclusion: A structured physical activity program reduced the MMD burden for an extended period, in part through enhanced recovery after the onset of disability and diminished risk for subsequent disability episodes. Primary Funding Source: National Institute on Aging, National Institutes of Health. PMID- 27669459 TI - Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine. AB - Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer. PMID- 27669460 TI - ChREBP regulates fructose-induced glucose production independently of insulin signaling. AB - Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, insulin fails to suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that carbohydrate-responsive element binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, plays a central role in this paradox. Administration of fructose increased hepatic hexose-phosphate levels, activated ChREBP, and caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis in mice. Activation of ChREBP was required for the increased expression of glycolytic and lipogenic genes as well as glucose-6-phosphatase (G6pc) that was associated with the effects of fructose administration. We found that fructose induced G6PC activity is a major determinant of hepatic glucose production and reduces hepatic glucose-6-phosphate levels to complete a homeostatic loop. Moreover, fructose activated ChREBP and induced G6pc in the absence of Foxo1a, indicating that carbohydrate-induced activation of ChREBP and G6PC dominates over the suppressive effects of insulin to enhance glucose production. This ChREBP/G6PC signaling axis is conserved in humans. Together, these findings support a carbohydrate-mediated, ChREBP-driven mechanism that contributes to hepatic insulin resistance. PMID- 27669461 TI - Targeting cancer metabolism by simultaneously disrupting parallel nutrient access pathways. AB - Oncogenic mutations drive anabolic metabolism, creating a dependency on nutrient influx through transporters, receptors, and macropinocytosis. While sphingolipids suppress tumor growth by downregulating nutrient transporters, macropinocytosis and autophagy still provide cancer cells with fuel. Therapeutics that simultaneously disrupt these parallel nutrient access pathways have potential as powerful starvation agents. Here, we describe a water-soluble, orally bioavailable synthetic sphingolipid, SH-BC-893, that triggers nutrient transporter internalization and also blocks lysosome-dependent nutrient generation pathways. SH-BC-893 activated protein phosphatase 2A (PP2A), leading to mislocalization of the lipid kinase PIKfyve. The concomitant mislocalization of the PIKfyve product PI(3,5)P2 triggered cytosolic vacuolation and blocked lysosomal fusion reactions essential for LDL, autophagosome, and macropinosome degradation. By simultaneously limiting access to both extracellular and intracellular nutrients, SH-BC-893 selectively killed cells expressing an activated form of the anabolic oncogene Ras in vitro and in vivo. However, slower growing, autochthonous PTEN-deficient prostate tumors that did not exhibit a classic Warburg phenotype were equally sensitive. Remarkably, normal proliferative tissues were unaffected by doses of SH-BC-893 that profoundly inhibited tumor growth. These studies demonstrate that simultaneously blocking parallel nutrient access pathways with sphingolipid-based drugs is broadly effective and cancer selective, suggesting a potential strategy for overcoming the resistance conferred by tumor heterogeneity. PMID- 27669463 TI - Rebound Syndrome in Multiple Sclerosis After Fingolimod Cessation. PMID- 27669462 TI - Mast cell desensitization inhibits calcium flux and aberrantly remodels actin. AB - Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have implicated mast cells (MCs) as the primary target cells for DS. Here, we developed a murine model of passive anaphylaxis with demonstrated MC involvement and an in vitro assay to evaluate the effect of DS on MCs. In contrast with previous reports, we determined that functional IgE remains on the cell surface of desensitized MCs following DS. Despite notable reductions in MC degranulation following DS, the high-affinity IgE receptor FcepsilonRI was still capable of transducing signals in desensitized MCs. Additionally, we found that displacement of the actin cytoskeleton and its continued association with FcepsilonRI impede the capacity of desensitized MCs to evoke the calcium response that is essential for MC degranulation. Together, these findings suggest that reduced degranulation responses in desensitized MCs arise from aberrant actin remodeling, providing insights that may lead to improvement of DS treatments for anaphylactic responses. PMID- 27669464 TI - Eliminating Routine Glucometer Readings in the Office Setting: Correcting a Foolish Consistency. PMID- 27669465 TI - Research questions: What questions need to be answered? What kind of answers does Endoscopy aim to publish? PMID- 27669466 TI - Finding disease patterns by shining a light on life: A work in progress. PMID- 27669467 TI - Addressing bias in polyp size measurement. PMID- 27669468 TI - Lumen restoration of long esophageal strictures. Should we shift towards endoscopic submucosal dissection? PMID- 27669469 TI - Reply to Mavrogenis et al. PMID- 27669470 TI - Peroral endoscopic myotomy for sigmoid-type achalasia: the myotomy length and ways to facilitate the procedure. PMID- 27669471 TI - Reply to Huo et al. PMID- 27669472 TI - Repeated cannulation attempts or late precut: which is more risky for post-ERCP pancreatitis? PMID- 27669473 TI - Reply to Kadayifci and Yildirim. PMID- 27669476 TI - French comment on article: European Society of Gastrointestinal Endoscopy - Establishing the key unanswered research questions within gastrointestinal endoscopy. PMID- 27669478 TI - French comment on article: Terminal digit preference biases polyp size measurements at endoscopy, computed tomographic colonography, and histopathology. PMID- 27669477 TI - French comment on article: Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in solid pancreatic masses. PMID- 27669479 TI - French comment on article: Narrow-band imaging vs. high definition white light for optical diagnosis of small colorectal polyps: a randomized multicenter trial. PMID- 27669480 TI - French comment on article: Magnetic endoscope imaging for routine colonoscopy: impact on propofol dosage and patient safety - a randomized trial. PMID- 27669482 TI - Video Comment on Klare et al. PMID- 27669481 TI - Video Comment on Plumb et al. PMID- 27669483 TI - Video Comment on Klare et al. PMID- 27669484 TI - Realizing the Full Potential of Precision Medicine in Health and Health Care. PMID- 27669485 TI - Guillain-Barre Syndrome and Cerebral Hemorrhage: Two Cases and Literature Review. AB - AIMS: The study aimed to investigate the potential relationships between Guillain Barre syndrome (GBS) and cerebral hemorrhage. METHODS: Two patients diagnosed with hemorrhagic stroke and GBS were reported. More specifically, the sequential occurrence and the corresponding mechanisms of these 2 diseases were analyzed. RESULTS: Two patients with cerebral hemorrhagic stroke developed progressive flaccid quadriplegia and life-threatening dyspnea in acute stage. Combined with the cerebrospinal fluid and electromyogram results, they were diagnosed as having acute GBS. It was found that GBS and cerebral nervous system (CNS) hemorrhage can occur successively, but the different sequences of occurrence had completely different pathogeneses. GBS following CNS hemorrhage was found to be related to the imbalance of systemic inflammatory responses, whereas CNS hemorrhage following GBS was due to blood vessel autonomous dysfunction and the use of immunoglobulin intravenously. Both groups of patients had only good prognoses when they were intensively observed. CONCLUSIONS: Despite being rare, GBS complicated with CNS hemorrhage deserves more attention due to its notable impact. PMID- 27669487 TI - Reply. PMID- 27669486 TI - Distinctive neuronal firing patterns in subterritories of the subthalamic nucleus. AB - OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for Parkinson's disease (PD). Anatomical connectivity analyses and task-related physiological studies have divided the STN into different functional domains: sensorimotor, limbic, and associative - located in its dorsolateral (dSTN), anteroventral (vSTN) and medial territories, respectively. Targeting sensorimotor STN is essential for stimulation efficacy and is supported by intraoperative micro-electrode recordings. A different neuronal signature in microelectrode recordings across STN subterritories was explored in this study. METHODS: Stable recordings from 30 PD patients were assigned to dSTN or vSTN by means of an anatomical method (based on fused computed tomography/magnetic resonance images) and through a priori tri-segmented partition of the recording itself. We computed the inter-spike interval (ISI) and ISI-characteristics, mean firing rate (MFR), discharge patterns and mean burst rate (MBR) of each detected single unit activity. RESULTS: We showed a different MBR between dSTN and vSTN (1.51+/-0.18 vs. 1.76+/-0.22events/minute, Wilcoxon rank sum test, p<0.05) and a trend in the difference between their MFR (12.78 vs. 15.05Hz, Wilcoxon rank sum test, p=0.053) only with the anatomically based method. CONCLUSION: Burst firing differs across STN subterritories. SIGNIFICANCE: Different functions of subthalamic domains might be reflected by distinctive burst signalling of its subterritories. PMID- 27669489 TI - Towards Enzyme-like, Sustainable Catalysis: Switchable, Highly Efficient Asymmetric Synthesis of Enantiopure Biginelli Dihydropyrimidinones or Hexahydropyrimidinones. AB - Organocatalysts displaying a network of cooperative hydrogen bonds (NCHB) have been employed in an enzyme-like manner for a direct, switchable synthesis of enantiopure hexahydropyrimidinones (HHPMs) or dihydropyrimidinones (DHPMs), which starts at a common, easily accessible alpha-ureidosulfone stage. The NCHB organocatalyst exploits all its potential as a pure hydrogen-bond biomimetic catalyst even in the presence of organic bases. This one-pot, diastereo- and enantioselective synthetic procedure has been proven to be robust, scalable, highly efficient, and environmentally benign. A straightforward and truly practical entry to enantiopure HHPMs is reported for the first time. PMID- 27669488 TI - Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance. AB - Recent studies have established that a complex community of microbes colonize the human urinary tract; however, their role in kidney transplant patients treated with prophylactic antibiotics remains poorly investigated. Our aim was to investigate the urinary microbiome of kidney transplant recipients. Urine samples from 21 patients after kidney transplantation and 8 healthy controls were collected. All patients received prophylactic treatment with the antibiotic combination trimethoprim-sulfamethoxazole. Metagenomic DNA was isolated from urine samples, sequenced using shotgun sequencing approach on Illumina HiSeq 2000 platform, and analyzed for microbial taxonomic and functional annotations. Our results demonstrate that the urine microbiome of kidney transplants was markedly different at all taxonomic levels from phyla to species, had decreased microbial diversity, and increased abundance of potentially pathogenic species compared with healthy controls. Specifically, at the phylum level, we detected a significant decrease in Actinobacteria and increase in Firmicutes due to increases in Enterococcus faecalis. In addition, there was an increase in the Proteobacteria due to increases in Escherichia coli. Analysis of predicted functions of the urinary metagenome revealed increased abundance of enzymes in the folate pathway including dihydrofolate synthase that are not inhibited by trimethoprim-sulfamethoxazole, but can augment folate metabolism. This report characterizes the urinary microbiome of kidney transplants using shotgun metagenomics approach. Our results indicate that the urinary microbiota may be modified in the context of prophylactic antibiotics, indicating that a therapeutic intervention may shift the urinary microbiota to select bacterial species with increased resistance to antibiotics. The evaluation and development of optimal prophylactic regimens that do not promote antibiotic resistance is an important future goal. PMID- 27669491 TI - AR Video Cover, November 2016 (ARV-15-0294.R1). PMID- 27669490 TI - Treatment of ibuprofen toxicity with serial charcoal hemoperfusion and hemodialysis in a dog. AB - OBJECTIVE: To describe the efficacy of serial charcoal hemoperfusion and hemodialysis in removing ibuprofen from a dog with severe clinical signs of toxicity. CASE SUMMARY: A dog ingested a minimum of 2,200 mg/kg of ibuprofen resulting in progressive neurologic dysfunction that progressed to a comatose state by the time of presentation. Extracorporeal charcoal hemoperfusion coupled serially with hemodialysis was performed to remove ibuprofen from this patient. Serial charcoal hemoperfusion and hemodialysis therapy resulted in complete reversal of the neurologic dysfunction in this dog. No evidence of acute kidney or hepatic injury was observed. Serum ibuprofen concentrations confirmed the efficacy of this treatment. NEW INFORMATION PROVIDED: This report details the technique for extracorporeal extraction of ibuprofen, a methodology that could be employed for other toxicities due to substances with similar pharmacokinetics. Complications and limitations (eg, saturation of the charcoal cartridge) of the therapy are discussed. PMID- 27669492 TI - Use of Multi-Intake Temporal Dominance of Sensations (TDS) to Evaluate the Influence of Cheese on Wine Perception. AB - Though the gastronomic sector recommends certain wine-cheese associations, there is little sensory evidence on how cheese influences the perception of wine. It was the aim of this study to dynamically characterize 4 wines as they would be perceived when consumed with and without cheese. The tasting protocol was based on multi-intake temporal dominance of sensations (TDS) coupled with hedonic rating. In the 1st session, 31 French wine and cheese consumers evaluated the wines (Pacherenc, Sancerre, Bourgogne, and Madiran) over 3 consecutive sips. In the following sessions, they performed the same task, but eating small portions of cheese (Epoisses, Comte, Roquefort, Crottin de Chavignol) between sips. All cheeses were tasted with all wines over 4 sessions. TDS data were mainly analyzed in terms of each attribute's duration of dominance by analysis of variance, multivariate analysis of variance, and canonical variate analysis. Results showed that cheese consumption had an impact (P < 0.1) on dominance duration of attributes and on preference for most wines. For example, in Madiran, all cheeses reduced dominance duration (P < 0.01) of astringency and sourness and increased duration of red fruit aroma. Although the number of consumers was small to make extended general conclusions on wine's preference, significant changes were observed before and after cheese intake. PMID- 27669494 TI - Column Theme: Groundwater Management Directions-Stewardship to Sustain Our Water Resources. PMID- 27669493 TI - Potato root system development and factors that determine its architecture. AB - The potato root system is often characterized as shallow and inefficient, with poor ability to extract water and minerals from the soil. Potato root system architecture (RSA) refers to its 3-dimensional structure as determined by adventitious root (AR) growth and branching through lateral roots (LR). Understanding how the root system develops holds potential to increase plant yield and optimize agricultural land use. Root system development was monitored in greenhouse-grown potato while a root-on-a-plate assay was developed to explore factors that affect AR and LR development. Expression study of LR-related genes was conducted. Transgenic plants carrying DR5:GFP and CycB1:GUS reporter genes were used to monitor auxin signaling and cell division during root primordia formation, respectively. Maximum root development occurred mainly during the 6 week post seed-tuber planting and slowed during the onset of tuberization. AR and LR development was coordinated - a positive correlation was found between the length of AR and LR and between LR length and number. The expression of LR related genes was higher in LR than in AR. High nitrate levels reduced LR number and length, however ablation of root-cap by high temperature (33 degrees C) or cutting resulted with enhanced formation of LR. Growth conditions affect AR and LR development in potato, determining the final architecture of its root system. The overall results indicate that LR formation in potato follows similar pattern as in model plants, facilitating study and manipulation of its RSA to improve soil exploitation and yield. PMID- 27669495 TI - Are executive functions related to emotional intelligence? A correlational study in schizophrenia and borderline personality disorder. AB - This research explored the relationship between executive functions (working memory and reasoning subtests of the Wechsler Adult Intelligence Scale, Trail Making and Stroop tests, fluency and planning tasks, and Wisconsin Card Sorting Test) and emotional intelligence measured by the Mayer-Salovey-Caruso Emotional Intelligence Test in patients with schizophrenia or borderline personality disorder compared to a control group. As expected, both clinical groups performed worse than the control group in executive functions and emotional intelligence, although the impairment was greater in the borderline personality disorder group. Executive functions significantly correlated with social functioning. Results are discussed in relation to the brain circuits that mediate executive functions and emotional intelligence and the findings obtained with other models of social cognition. PMID- 27669496 TI - Serum high-sensitivity C-reactive protein: A delicate sentinel elevated in drug free acutely agitated patients with schizophrenia. AB - Increased levels of high-sensitivity C reactive protein (hsCRP) have been reported in schizophrenia, but to date, no study is designed to examine serum hsCRP in acutely agitated patients with schizophrenia, an extreme state that requires immediate diagnosis and medical treatment. Serum hsCRP levels were assessed in 32 clinically acutely agitated patients and 42 healthy control subjects matched for demographic properties. Further, serum hsCRP levels in acutely agitated patients were compared with control subjects and with the levels after the patients were treated with anti-psychiatric medications. Meanwhile, the influence of clinical subtypes, family history, and gender, as well as the levels of white blood cell (WBC) counts were also considered. In results, serum hsCRP levels were significantly higher in acutely agitated patients with schizophrenia than in healthy subjects. The elevation of serum hsCRP in patients was not affected by gender, family history (P>0.05), and clinical classification of schizophrenia (P>0.05). However, the elevation of hsCRP was suppressed by the medical treatment for schizophrenia with acute agitation (P<0.05). In addition, WBC counts, another inflammation-related indicator, were also increased significantly in acutely agitated patients compared with healthy subjects, consistent with the elevation of serum hsCRP. In conclusion, hsCRP is an important indicator of immune alterations in the pathogenesis of schizophrenia and has potential to be developed into a sensitive marker for the acute agitation in schizophrenia. PMID- 27669497 TI - Evaluation of rapid maxillary expansion through acoustic emission technique and relative soft tissue attenuation. AB - OBJECTIVES: Acoustic emission (AE) is a non-destructive test to detect energy release. This technique was applied during rapid maxillary expansion (RME) to evaluate the reaction of the craniofacial skeleton. MATERIALS AND METHODS: A swine model was analysed. Soft tissues were removed from two heads, while other two were preserved intact. A palatal expander (PE) was positioned and AE sensors were placed on the intermaxillary, fronto-nasal, and maxillo-lacrimal sutures. The PE was activated and AE recorded during RME. Differences between parameters were analysed with Mann-Whitney U test and Kruskal-Wallis test, and correlations with Spearman-Rho test (significance p<0.05). RESULTS: PE activations were accompanied by clusters of AE hits. In the presence of soft tissues, amplitudes were generally lower (p<0.001) and durations were higher (p<0.001). No differences were found in the respective energy values. Differences were found in the AE (p<0.05) among the four channels, with AE characterised by higher values in proximity of the maxillo-lacrimal sutures. High-energy hits were represented by burst-type waves, and low-energy ones by continuous-type. CONCLUSIONS: Although soft tissues create possible attenuation of the signal, AE can be detected during RME with sensors on the skin. AE provided further information of energy release, on top of the mechanical parameters. Source location was one of the main limitations. PMID- 27669499 TI - Remarkably Improved Electrochemical Performance of Li- and Mn-Rich Cathodes upon Substitution of Mn with Ni. AB - Li- and Mn-rich transition-metal oxides of layered structure are promising cathodes for Li-ion batteries because of their high capacity values, >=250 mAh g 1. These cathodes suffer from capacity fading and discharge voltage decay upon prolonged cycling to potential higher than 4.5 V. Most of these Li- and Mn-rich cathodes contain Ni in a 2+ oxidation state. The fine details of the composition of these materials may be critically important in determining their performance. In the present study, we used Li1.2Ni0.13Mn0.54Co0.13O2 as the reference cathode composition in which Mn ions are substituted by Ni ions so that their average oxidation state in Li1.2Ni0.27Mn0.4Co0.13O2 could change from 2+ to 3+. Upon substitution of Mn with Ni, the specific capacity decreases but, in turn, an impressive stability was gained, about 95% capacity retention after 150 cycles, compared to 77% capacity retention for Li1.2Ni0.13Mn0.54Co0.13O2 cathodes when cycled at a C/5 rate. Also, a higher average discharge voltage of 3.7 V is obtained for Li1.2Ni0.27Mn0.4Co0.13O2 cathodes, which decreases to 3.5 V after 150 cycles, while the voltage fading of cathodes comprising the reference material is more pronounced. The Li1.2Ni0.27Mn0.4Co0.13O2 cathodes also demonstrate higher rate capability compared to the reference Li1.2Ni0.13Mn0.54Co0.13O2 cathodes. These results clearly indicate the importance of the fine composition of cathode materials containing the five elements Li, Mn, Ni, Co, and O. The present study should encourage rigorous optimization efforts related to the fine composition of these cathode materials, before external means such as doping and coating are applied. PMID- 27669498 TI - Biocompatibility of implantable materials: An oxidative stress viewpoint. AB - Oxidative stress occurs when the production of oxidants surpasses the antioxidant capacity in living cells. Oxidative stress is implicated in a number of pathological conditions such as cardiovascular and neurodegenerative diseases but it also has crucial roles in the regulation of cellular activities. Over the last few decades, many studies have identified significant connections between oxidative stress, inflammation and healing. In particular, increasing evidence indicates that the production of oxidants and the cellular response to oxidative stress are intricately connected to the fate of implanted biomaterials. This review article provides an overview of the major mechanisms underlying the link between oxidative stress and the biocompatibility of biomaterials. ROS, RNS and lipid peroxidation products act as chemo-attractants, signalling molecules and agents of degradation during the inflammation and healing phases. As chemo attractants and signalling molecules, they contribute to the recruitment and activation of inflammatory and healing cells, which in turn produce more oxidants. As agents of degradation, they contribute to the maturation of the extracellular matrix at the healing site and to the degradation of the implanted material. Oxidative stress is itself influenced by the material properties, such as by their composition, their surface properties and their degradation products. Because both cells and materials produce and react with oxidants, oxidative stress may be the most direct route mediating the communication between cells and materials. Improved understanding of the oxidative stress mechanisms following biomaterial implantation may therefore help the development of new biomaterials with enhanced biocompatibility. PMID- 27669500 TI - Mapping current research trends on neuromuscular risk factors of non-contact ACL injury. AB - The aim of this systematic review was (i) to identify neuromuscular markers that have been predictive of a primary non-contact ACL injury, (ii) to assess whether proposed risk factors have been supported or refuted in the literature from cohort and case-control studies, and (iii) to reflect on the body of research that aims at developing field based tools to assess risk through an association with these risk factors. Electronic searches were undertaken, of PubMed, SCOPUS, Web of Science, CINAHL and SPORTDiscus examining neuromuscular risk factors associated with ACL injury published between January 1990 and July 2015. The evidence supporting neuromuscular risk factors of ACL injury is limited where only 4 prospective cohort studies were found. Three of which looked into muscular capacity and one looked into muscular activation patterns but none of the studies found strong evidence of how muscular capacity or muscular activation deficits are a risk factor for a primary non-contact ACL injury. A number of factors associated to neural control and muscular capacity have been suggested to be related to non-contact ACL injury risk but the level of evidence supporting these risk factors remains often elusive, leaving researchers and practitioners uncertain when developing evidence-based injury prevention programs. PMID- 27669501 TI - CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer. AB - INTRODUCTION: Immunological response to human papillomavirus (HPV) in the development and progression of HPV16+ oropharyngeal squamous cell carcinoma (OPSCC) (accounting for the majority of viral associated cases) is largely unknown and may provide important insights for new therapeutic strategies. METHODS: In this prospective clinical trial (UKCRN11945), we examined cell mediated immune responses to HPV16 E2, E6 and E7 in peripheral blood using IFN gamma enzyme-linked immunosorbent spot assay. CD56+, CD4+, CD8+ and regulatory T cell frequencies were also discerned by flow cytometry. Fifty-one study participants with oropharyngeal carcinoma were recruited. Control subjects were those undergoing tonsillectomy for benign disease. All patients were treated with curative intent by radiotherapy +/- chemotherapy. Disease-specific survival was investigated by multivariate analysis. RESULTS: HPV16 DNA was detected in 41/51 of the OPSCC participants. T cell responses against HPV16 E6 or E7 peptides were detected in 33/51 evaluable patients, respectively and correlated with HPV status. Matched pre- and post-treatment T cell responses were available for 39/51 OPSCC cases. Within the whole cohort, elevated post-treatment CD8+ response to HPV16 E7 correlated with longer disease free survival (multivariate DFS p < 0.03). Within the HPV + OPSCC cohort, a significant increase in regulatory T cells (p < 0.02) was noted after treatment. CONCLUSIONS: This is the first study to provide survival data in OPSCC stratified by cell-mediated immune response to HPV16 peptides. Within the HPV16+ OPSCC cohort, enhanced immunoreactivity to antigen E7 was linked to improved survival. An increase in regulatory T cell frequencies after treatment may suggest that immunosuppression can contribute to a reduced HPV-specific cell-mediated response. PMID- 27669503 TI - Effects of time interval between primary melanoma excision and sentinel node biopsy on positivity rate and survival. AB - BACKGROUND: Sentinel node biopsy (SNB) is essential for adequate melanoma staging. Most melanoma guidelines advocate to perform wide local excision and SNB as soon as possible, causing time pressure. OBJECTIVE: To investigate the role of time interval between melanoma diagnosis and SNB on sentinel node (SN) positivity and survival. METHODS: This is a retrospective observational study concerning a cohort of melanoma patients from four European Organization for Research and Treatment of Cancer Melanoma Group tertiary referral centres from 1997 to 2013. A total of 4124 melanoma patients underwent SNB. Patients were selected if date of diagnosis and follow-up (FU) information were available, and SNB was performed in <180 d. A total of 3546 patients were included. Multivariable logistic regression and Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to positivity rate, disease-free survival (DFS) and melanoma-specific survival (MSS). FINDINGS: Median time interval was 43 d (interquartile range [IQR] 29-60 d), and 705 (19.9%) of 3546 patients had a positive SN. Sentinel node positivity was equal for early surgery (<=43 d) versus late surgery (>43 d): 19.7% versus 20.1% (p = 0.771). Median FU was 50 months (IQR 24-84 months). Sentinel node metastasis (hazard ratio [HR] 3.17, 95% confidence interval [95% CI] 2.53-3.97), ulceration (HR 1.99, 95% CI 1.58-2.51), Breslow thickness (HR 1.06, 95% CI 1.04-1.08), and male gender (HR 1.58, 95% CI 1.26-1.98) (all p < 0.00001) were independently associated with worse MSS and DFS; time interval was not. INTERPRETATION: No effect of time interval between melanoma diagnosis and SNB on 5-year survival or SN positivity rate was found for a time interval of up to 3 months. This information can be used to counsel patients and remove strict time limits from melanoma guidelines. PMID- 27669502 TI - Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells. AB - BACKGROUND: The development of intrinsic and acquired resistance to antineoplastic agents is a major obstacle to successful chemotherapy in ovarian cancers. Identification and characterisation of chemoresponse-associated biomarkers are of paramount importance for novel therapeutic development. METHODS: Global RNA expression profiles were obtained by high-throughput microarray analysis. Cell cycle, proliferation rate, and paclitaxel sensitivity of ovarian cancer cells harbouring cyclin A1-inducible expression construct were compared with and without tetracycline induction, as well as when the cyclin A1 expression was suppressed by short inhibiting RNA (siRNA). Cellular senescence was evaluated by beta-galactosidase activity staining. RESULTS: Global RNA expression profiling and subsequent correlation studies of gene expression level and drug response has identified that elevated expression of cyclin A1 (CCNA1) was significantly associated with cellular resistance to paclitaxel, doxorubicin and 5-fluorouracil. The role of cyclin A1 in paclitaxel resistance was confirmed in ovarian cancer cells that harbour an inducible cyclin A1 expression construct, which showed reduced paclitaxel-mediated growth inhibition and apoptosis when cyclin A1 expression was induced, whereas downregulation of cyclin A1 expression in the same cell lines using cyclin A1-specific siRNAs sensitised the cells to paclitaxel toxicity. However, ovarian cancer cells with ectopic expression of cyclin A1 demonstrated slowdown of proliferation and senescence-associated beta galactosidase activity. CONCLUSIONS: Our profiling and correlation studies have identified cyclin A1 as one chemoresistance-associated biomarker in ovarian cancer. The results of the characterisation studies suggest that cyclin A1 functions as an oncogene that controls proliferative and survival activities in tumourigenesis and chemoresistance of ovarian cancer. PMID- 27669504 TI - Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma. AB - AIM: The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV-) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). PATIENTS AND METHODS: A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000-2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV-. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV- cohorts separately. RESULTS: A total of 404 HPV+ and 255 HPV- LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow up was 4.3 (0.5-11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m2 subgroups were 52%, 60%, and 72% (P = 0.001) for the HPV- and 91%, 90%, and 91% (P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m2 for the HPV- (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3-0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4-1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset (N = 107) with cisplatin >200 mg/m2 (HR 0.5, 95% CI: 0.2-1.1, P = 0.07). CONCLUSIONS: A survival benefit of cisplatin dose >200 mg/m2 is evident for HPV- LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose. PMID- 27669505 TI - Biomimetic ELISA detection of malachite green based on magnetic molecularly imprinted polymers. AB - A direct competitive enzyme-linked immunosorbent assay (ELISA) method was used for the detection of malachite green (MG) with a high sensitivity and selectivity using magnetic molecularly imprinted polymers (MMIPs) as a bionic antibody. MMIPs were prepared through emulsion polymerization using Fe3O4 nanoparticles as magnetic nuclei, MG as a template, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinking agent and span 80/tween-80 as mixed emulsifiers. The MMIPs were characterized by scanning electron micrographs (SEM), thermal-gravimetric analyzer (TGA), Fourier transform infrared spectrometer (FT-IR) and vibrating sample magnetometer (VSM), respectively. A high magnetic saturation value of 54.1emug-1 was obtained, resulting in rapid magnetic separation of MMIPs with an external magnet. The IC50 of the established ELISA method was 20.1MUgL-1 and the detection limit (based on IC85) was 0.1MUgL-1. The MMIPs exhibited high selective binding capacity for MG with cross-reactivities less than 3.9% for MG structural analogues. The MG spiking recoveries were 85.0%-106% with the relative standard deviations less than 4.7%. The results showed that the biomimetic ELISA method by using MMIPs as bionic antibody could be used to detect MG rapidly in fish samples with a high sensitivity and accuracy. PMID- 27669506 TI - Multi-mycotoxins analysis in Pheretima using ultra-high-performance liquid chromatography tandem mass spectrometry based on a modified QuEChERS method. AB - A sensitive and high-throughput method was established and validated for the simultaneous determination of 22 mycotoxins in Pheretima aspergillum (E.Perrier) and Pheretima guillelmi (Michaelsen). A modified Quick Easy Cheap Effective Rugged and Safe (QuEChERS) method was used for sample preparation with recoveries ranging from 73% to 105% with relative standard deviations (RSDs) <8.0% for all target analytes. Ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) was applied for separation and detection in ESI (+) and ESI (-) modes with the limits of detection (LOD) in the range of 0.05-10MUgkg-1. The 22 compounds could be accurately quantified in the 0.5-1000MUgkg-1 concentration range with correlation coefficients >0.99. In all cases, the intra- and inter-day precisions were lower than 6% and 10%, respectively. Matrix-matched calibration was utilized for quantification purposes to compensate for the matrix effects. Furthermore, the established method was successfully applied in 17 batches of normal real samples collected from different areas of China and 2 batches of moldy samples due to improper storage, only mold-contaminated samples were confirmed to have fumonisin B1 (FB1) and fumonisin B2 (FB2) contamination at 2.54-3.78MUgkg-1. The constructed method could serve as a practical application of the UHPLC-MS/MS method for the trace analysis of multiple mycotoxins in complex matrixes, especially for those with high lipid contents. PMID- 27669507 TI - Simultaneous targeted analysis of trimethylamine-N-oxide, choline, betaine, and carnitine by high performance liquid chromatography tandem mass spectrometry. AB - Trimethylamine-N-oxide (TMAO) is a metabolite generated from choline, betaine and carnitine in a gut microbiota-dependent way. This molecule is associated with development of atherosclerosis and cardiovascular events. A sensitive liquid chromatographic electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination of TMAO related molecules including TMAO, betaine, choline, and carnitine in mouse plasma. Analytes are extracted after protein precipitation by methanol and subjected to LC-ESI-MS/MS without preliminary derivatization. Separation of analytes was achieved on an amide column with acetonitrile-water as the mobile phase. This method has been fully validated in this study in terms of selectivity, linearity, sensitivity, precision, accuracy, and carryover effect, and the stability of the analyte under various conditions has been confirmed. This developed method has successfully been applied to plasma samples of our mouse model. PMID- 27669508 TI - Utility of a Phylogenetic Perspective in Structural Analysis of CYP72A Enzymes from Flowering Plants. AB - Plant adaptation to external pressures depends on functional diversity in cytochrome P450 (CYP) enzymes. CYPs contain structural domains necessary for the characteristic P450 fold that allows monooxygenation, but they also have great variation in substrate binding affinity. Plant genomes typically contain hundreds of CYPs that contribute to essential functions and species-specific metabolism. The CYP72A subfamily is conserved in angiosperms but its contribution to physiological functions is largely unknown. With genomic information available for many plants, a focused analysis of CYP subfamily diversity is important to understand the contributions of these enzymes to plant evolution. This study examines the extent to which independent gene duplication and evolution have contributed to structural diversification of CYP72A enzymes in different plant lineages. CYP72A genes are prevalent across angiosperms, but the number of genes within each genome varies greatly. The prevalence of CYP72As suggest that the last common ancestor of flowering plants contained a CYP72A sequence, but gene duplication and retention has varied greatly for this CYP subfamily. Sequence comparisons show that CYP72As are involved in species-specific metabolic functions in some plants while there is likely functional conservation between closely related species. Analysis of structural and functional domains within groups of CYP72As reveals clade-specific residues that contribute to functional constraints within subsets of CYP72As. This study provides a phylogenetic framework that allows comparisons of structural features within subsets of the CYP72A subfamily. We examined a large number of sequences from a broad collection of plant species to detect patterns of functional conservation across the subfamily. The evolutionary relationships between CYPs in plant genomes are an important component in understanding the evolution of biochemical diversity in plants. PMID- 27669509 TI - Rapid Multiplexed Immunoassay for Detection of Antibodies to Kaposi's Sarcoma Associated Herpesvirus. AB - Diagnosis of KSHV-infected individuals remains a challenge. KSHV prevalence is high in several populations with high prevalence of HIV, leading to increased risk of development of Kaposi's sarcoma (KS). While current assays are reliable for detecting antibodies to KSHV, none are routinely utilized to identify individuals with KSHV infection and thus at increased risk for KS due to assay complexity, lack of access to testing, and cost, particularly in resource-limited settings. Here we describe the addition of KSHV proteins LANA and K8.1 to a previously evaluated HIV/co-infection multiplexed fluorescence immunoassay system. This study demonstrates assay performance by measuring antibody reactivity for KSHV and HIV-1 in a collection of clinical specimens from patients with biopsy-proven KS and sourced negative controls. The KSHV assay correctly identified 155 of 164 plasma samples from patients with biopsy-proven KS and 85 of 93 KSHV antibody (Ab)-negative samples for a sensitivity of 95.1% and specificity of 91.4%. Assay performance for HIV-1 detection was also assessed with 100% agreement with independently verified HIV-1 Ab-positive and Ab-negative samples. These results demonstrate good sensitivity and specificity for detection of antibody to KSHV antigens, and demonstrate the potential for multiplexed co infection testing in resource-limited settings to identify those at increased risk for HIV-1-related complications. PMID- 27669511 TI - Effect of Vitamin A on Listeria monocytogenes Infection in a Silkworm Model. AB - Insect infection models have been used increasingly to study various pathogenic agents in evaluations of pathogenicity and drug efficacy. In this study, we demonstrated that larvae of the silkworm Bombyx mori are useful for studying Listeria monocytogenes infections in insects. Infection with the L. monocytogenes wild-type strain induced silkworm death. Infection by a listeriolysin O (LLO) deletion mutant also induced silkworm death, but the bacterial numbers in silkworms were lower than those of the wild-type strain. Intracellular growth was observed when the silkworm ovary-derived cell line BmN4 was infected with the wild-type strain. Explosive replication was not observed in BmN4 cells infected with the LLO mutant and the bacterial numbers of the LLO mutant were lower than those of the wild-type strain. Pretreatment with vitamin A did not affect silkworm mortality after bacterial infection, but the efficiency of infecting the hemocytes and BmN4 cells was decreased with vitamin A treatment. Our results indicate that silkworm larvae are a useful insect infection model for L. monocytogenes and that vitamin A has protective effects against bacterial infection in silkworms. PMID- 27669510 TI - A Structural Equation Model of HIV-Related Stigma, Racial Discrimination, Housing Insecurity and Wellbeing among African and Caribbean Black Women Living with HIV in Ontario, Canada. AB - African and Caribbean Black women in Canada have new HIV infection rates 7 times higher than their white counterparts. This overrepresentation is situated in structural contexts of inequities that result in social, economic and health disparities among African and Caribbean Black populations. Economic insecurity is a distal driver of HIV vulnerability, reducing access to HIV testing, prevention and care. Less is known about how economic insecurity indicators, such as housing security, continue to influence the lives of women living with HIV following HIV positive diagnoses. The aim of this study was to test a conceptual model of the pathways linking HIV-related stigma, racial discrimination, housing insecurity, and wellbeing (depression, social support, self-rated health). We implemented a cross-sectional survey with African and Caribbean Black women living with HIV in 5 Ontario cities, and included 157 participants with complete data in the analyses. We conducted structural equation modeling using maximum likelihood estimation to evaluate the hypothesized conceptual model. One-fifth (22.5%; n = 39) of participants reported housing insecurity. As hypothesized, racial discrimination had significant direct effects on: HIV-related stigma, depression and social support, and an indirect effect on self-rated health via HIV-related stigma. HIV-related stigma and housing insecurity had direct effects on depression and social support, and HIV-related stigma had a direct effect on self rated health. The model fit the data well: chi2 (45, n = 154) = 54.28, p = 0.387; CFI = 0.997; TLI = 0.996; RMSEA = 0.016. Findings highlight the need to address housing insecurity and intersecting forms of stigma and discrimination among African and Caribbean Black women living with HIV. Understanding the complex relationships between housing insecurity, HIV-related stigma, racial discrimination, and wellbeing can inform multi-level interventions to reduce stigma and enhance health. PMID- 27669512 TI - Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population Based Cross-Sectional Study in South-Western Sardinia. AB - BACKGROUND: South-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS. METHODS: Geochemical data on HM, UV exposure, urbanization and epidemiological MS data were available for all SWS municipalities. Principal Component Analysis (PCA) was applied to the geochemical data to reduce multicollinearity and confounding criticalities. Generalized Linear Mixed Models (GLMM) were applied to evaluate the causal effects of the potential risk factors, and a model selection was performed using Akaike Information Criterion. RESULTS: The PCA revealed that copper (Cu) does not cluster, while two component scores were extracted: 'basic rocks', including cobalt, chromium and nickel, and 'ore deposits', including lead and zinc. The selected multivariable GLMM highlighted Cu and sex as MS risk factors, adjusting for age and 'ore deposits'. When the Cu concentration increases by 50 ppm, the MS odds are 2.827 (95% CI: 1.645; 5.07) times higher; females have a MS odds 2.04 times (95% CI: 1.59; 2.60) higher than males. CONCLUSIONS: The high frequency of MS in industrialized countries, where pollution by HM and CO poisoning is widespread, suggests a relationship between environmental exposure to metals and MS. Hence, we suggested a role of Cu homeostasis in MS. This is a preliminary study aimed at generating hypotheses that will need to be confirmed further. PMID- 27669513 TI - Sickness Presence among Disabled Workers at the University Medical Centre Ljubljana. AB - OBJECTIVES: The aim of the article is to investigate the differences in sickness present and non-sickness present in the group of disabled health care professionals. METHODS: Data were gathered from all disabled health care professionals suffering from invalidity of category II or III who were identified in the research among all health care professionals at the University Medical Centre Ljubljana and who were employed there in the period between 1 January 2010 and 31 December 2010. Each employee obtained a questionnaire composed of three standardized international questionnaires. RESULTS: There were 248 disabled workers of the II. and III. category of invalidity among the participants. Disabled sickness present reported to have more chronic diseases than disabled non-sickness present (OR = 57.0; 95% CI = 24.4-133.2), lower salary when on sick leave (OR = 13.1; 95% CI = 5.7-30.2) and poor self-rated health (OR = 5.8; 95% CI = 2.7-12.3). CONCLUSIONS: The prerequisite for sickness presence among disabled workers is their chronic bad health. It is also formally recognized with the degree of disability. Economic factors are among the most important to direct disabled workers towards sickness presence. The results indicate that workplaces are not adapted to disabled workers in regard to their limitations. PMID- 27669514 TI - Risk Factors Associated with Overweight among Adolescents in Serbia. AB - INTRODUCTION: The pandemic of obesity in adolescents is one of the challenges of public health. AIM: The aim of this study was to examine the association of overweight with demographic, socioeconomic and lifestyle factors among Serbian adolescents. METHOD: A cross-sectional study of 2139 adolescents aged 10 to 19 years was carried out. Data used in this study were from the 2006 Health Survey. In accordance with the international sex- and age-specific Body Mass Index cut off points, all participants were classified as being normal weight or overweight, including obese. The association between the risk factors and overweight were examined using a multivariate logistic regression model. RESULTS: The study showed that 28.9% of boys and 17.0% of girls were overweight, while 14.5% of boys and 8.1% of girls were obese. Boys were more likely to be overweight/obese, compared with girls. Being younger (p< 0.01 for 14 to 15 years) and (p< 0.01, for 16 to 19 years), engaging in physical activities that last less than 7 hours a week, in such a manner that they breathe quickly and become sweaty, (p< 0.01) and skipping breakfast (p< 0.05) were risk factors significantly associated with overweight among adolescents. No significant association was found with wealth index. CONCLUSION: These findings should be an integral part of further preventive interventions, especially oriented towards younger adolescents, who are physically inactive, have a habit of skipping breakfast and are boys. PMID- 27669515 TI - Management of Gastrointestinal Disorders in Central and Eastern Europe: Self Reported Practice of Primary Care Physicians. AB - BACKGROUND: Gastrointestinal disorders account for 7-10% of all consultations in primary care. General practitioners' management of digestive disorders in Central and Eastern European countries is largely unknown. AIMS: To identify and compare variations in the self-perceived responsibilities of general practitioners in the management of digestive disorders in Central and Eastern Europe. METHODS: A cross sectional survey of a randomized sample of primary care physicians from 9 countries was conducted. An anonymous questionnaire was sent via post to primary care doctors. RESULTS: We received 867 responses; the response rate was 28.9%. Over 70% of respondents reported familiarity with available guidelines for gastrointestinal diseases. For uninvestigated dyspepsia in patients under 45 years, the "test and treat" strategy was twice as popular as "test and scope". The majority (59.8%) of family physicians would refer patients with rectal bleeding without alarm symptoms to a specialist (from 7.6% of doctors in Slovenia to 85.1% of doctors in Bulgaria; p<0.001). 93.4% of respondents declared their involvement in colorectal cancer screening. In the majority of countries, responding doctors most often reported that they order fecal occult blood tests. The exceptions were Estonia and Hungary, where the majority of family physicians referred patients to a specialist (p<0.001). CONCLUSIONS: Physicians from Central and Eastern European countries understood the need for the use of guidelines for the care of patients with gastrointestinal problems, but there is broad variation between countries in their management. Numerous efforts should be undertaken to establish and implement international standards for digestive disorders' management in general practice. PMID- 27669517 TI - Dissipation induced by phonon elastic scattering in crystals. AB - We demonstrate that the phonon elastic scattering leads to a dominant dissipation in crystals at low temperature. The two-level systems (TLSs) should be responsible for the elastic scattering, whereas the dissipation induced by static point defects (SPDs) can not be neglected. One purpose of this work is to show how the energy splitting distribution of the TLS ensemble affects the dissipation. Besides, this article displays the proportion of phonon-TLS elastic scattering to total phonon dissipation. The coupling coefficient of phonon-SPD scattering and the constant P0 of the TLS distribution are important that we estimate their magnitudes in this paper. Our results is useful to understand the phonon dissipation mechanism, and give some clues to improve the performance of mechanical resonators, apply the desired defects, or reveal the atom configuration in lattice structure of disordered crystals. PMID- 27669516 TI - Voice Disorders in Occupations with Vocal Load in Slovenia. AB - AIM: The aim of this paper is to compare the prevalence of voice disorders and the risk factors for them in different occupations with a vocal load in Slovenia. METHODS: A meta-analysis of six different Slovenian studies involving teachers, physicians, salespeople, catholic priests, nurses and speech-and-language therapists (SLTs) was performed. In all six studies, similar questions about the prevalence of voice disorders and the causes for them were included. RESULTS: The comparison of the six studies showed that more than 82% of the 2347 included subjects had voice problems at some time during their career. The teachers were the most affected by voice problems. The prevalent cause of voice problems was the vocal load in teachers and salespeople and respiratory-tract infections in all the other occupational groups. When the occupational groups were compared, it was stated that the teachers had more voice problems and showed less care for their voices than the priests. The physicians had more voice problems and showed better consideration of vocal hygiene rules than the SLTs. The majority of all the included subjects did not receive instructions about voice care during education. CONCLUSIONS: In order to decrease the prevalence of voice disorders in vocal professionals, a screening program is recommended before the beginning of their studies. Regular courses on voice care and proper vocal technique should be obligatory for all professional voice users during their career. The inclusion of dysphonia in the list of occupational diseases should be considered in Slovenia as it is in some European countries. PMID- 27669519 TI - The dissemination of multidrug-resistant Enterobacter cloacae throughout the UK and Ireland. AB - Enterobacter cloacae is a clinically important Gram-negative member of the Enterobacteriaceae, which has increasingly been recognized as a major pathogen in nosocomial infections. Despite this, knowledge about the population structure and the distribution of virulence factors and antibiotic-resistance determinants of this species is scarce. In this study, we analysed a systematic collection of multidrug-resistant E. cloacae isolated between 2001 and 2011 from bloodstream infections across hospitals in the UK and Ireland. We found that the population is characterized by the presence of multiple clones formed at widely different time periods in the past. The clones exhibit a high degree of geographical heterogeneity, which indicates extensive dissemination of these E. cloacae clones across the UK and Ireland. These findings suggest that a diverse, community based, commensal population underlies multidrug-resistant E. cloacae infections within hospitals. PMID- 27669518 TI - Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling. AB - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID- 27669520 TI - Modeling Periodic Impulsive Effects on Online TV Series Diffusion. AB - BACKGROUND: Online broadcasting substantially affects the production, distribution, and profit of TV series. In addition, online word-of-mouth significantly affects the diffusion of TV series. Because on-demand streaming rates are the most important factor that influences the earnings of online video suppliers, streaming statistics and forecasting trends are valuable. In this paper, we investigate the effects of periodic impulsive stimulation and pre launch promotion on on-demand streaming dynamics. We consider imbalanced audience feverish distribution using an impulsive susceptible-infected-removed(SIR)-like model. In addition, we perform a correlation analysis of online buzz volume based on Baidu Index data. METHODS: We propose a PI-SIR model to evolve audience dynamics and translate them into on-demand streaming fluctuations, which can be observed and comprehended by online video suppliers. Six South Korean TV series datasets are used to test the model. We develop a coarse-to-fine two-step fitting scheme to estimate the model parameters, first by fitting inter-period accumulation and then by fitting inner-period feverish distribution. RESULTS: We find that audience members display similar viewing habits. That is, they seek new episodes every update day but fade away. This outcome means that impulsive intensity plays a crucial role in on-demand streaming diffusion. In addition, the initial audience size and online buzz are significant factors. On-demand streaming fluctuation is highly correlated with online buzz fluctuation. CONCLUSION: To stimulate audience attention and interpersonal diffusion, it is worthwhile to invest in promotion near update days. Strong pre-launch promotion is also a good marketing tool to improve overall performance. It is not advisable for online video providers to promote several popular TV series on the same update day. Inter-period accumulation is a feasible forecasting tool to predict the future trend of the on-demand streaming amount. The buzz in public social communities also represents a highly correlated analysis tool to evaluate the advertising value of TV series. PMID- 27669521 TI - Feasibility and Safety of Evaluating Patients with Prior Coronary Artery Disease Using an Accelerated Diagnostic Algorithm in a Chest Pain Unit. AB - An accelerated diagnostic protocol for evaluating low-risk patients with acute chest pain in a cardiologist-based chest pain unit (CPU) is widely employed today. However, limited data exist regarding the feasibility of such an algorithm for patients with a history of prior coronary artery disease (CAD). The aim of the current study was to assess the feasibility and safety of evaluating patients with a history of prior CAD using an accelerated diagnostic protocol. We evaluated 1,220 consecutive patients presenting with acute chest pain and hospitalized in our CPU. Patients were stratified according to whether they had a history of prior CAD or not. The primary composite outcome was defined as a composite of readmission due to chest pain, acute coronary syndrome, coronary revascularization, or death during a 60-day follow-up period. Overall, 268 (22%) patients had a history of prior CAD. Non-invasive evaluation was performed in 1,112 (91%) patients. While patients with a history of prior CAD had more comorbidities, the two study groups were similar regarding hospitalization rates (9% vs. 13%, p = 0.08), coronary angiography (13% vs. 11%, p = 0.41), and revascularization (6.5% vs. 5.7%, p = 0.8) performed during CPU evaluation. At 60 days the primary endpoint was observed in 12 (1.6%) and 6 (3.2%) patients without and with a history of prior CAD, respectively (p = 0.836). No mortalities were recorded. To conclude, Patients with a history of prior CAD can be expeditiously and safely evaluated using an accelerated diagnostic protocol in a CPU with outcomes not differing from patients without such a history. PMID- 27669522 TI - Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index. PMID- 27669523 TI - Competencies and Tools to Shift Payments From Volume to Value. PMID- 27669525 TI - What to Do When K-Means Clustering Fails: A Simple yet Principled Alternative Algorithm. AB - The K-means algorithm is one of the most popular clustering algorithms in current use as it is relatively fast yet simple to understand and deploy in practice. Nevertheless, its use entails certain restrictive assumptions about the data, the negative consequences of which are not always immediately apparent, as we demonstrate. While more flexible algorithms have been developed, their widespread use has been hindered by their computational and technical complexity. Motivated by these considerations, we present a flexible alternative to K-means that relaxes most of the assumptions, whilst remaining almost as fast and simple. This novel algorithm which we call MAP-DP (maximum a-posteriori Dirichlet process mixtures), is statistically rigorous as it is based on nonparametric Bayesian Dirichlet process mixture modeling. This approach allows us to overcome most of the limitations imposed by K-means. The number of clusters K is estimated from the data instead of being fixed a-priori as in K-means. In addition, while K means is restricted to continuous data, the MAP-DP framework can be applied to many kinds of data, for example, binary, count or ordinal data. Also, it can efficiently separate outliers from the data. This additional flexibility does not incur a significant computational overhead compared to K-means with MAP-DP convergence typically achieved in the order of seconds for many practical problems. Finally, in contrast to K-means, since the algorithm is based on an underlying statistical model, the MAP-DP framework can deal with missing data and enables model testing such as cross validation in a principled way. We demonstrate the simplicity and effectiveness of this algorithm on the health informatics problem of clinical sub-typing in a cluster of diseases known as parkinsonism. PMID- 27669524 TI - Effectiveness of Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries Aged 70 to 79 Years: A Prospective Observational Study. AB - Background: No randomized, controlled trials of screening colonoscopy have been completed, and ongoing trials exclude persons aged 75 years or older. The Medicare program, however, reimburses screening colonoscopy without an upper age limit. Objective: To evaluate the effectiveness and safety of screening colonoscopy to prevent colorectal cancer (CRC) in persons aged 70 to 74 and those aged 75 to 79 years. Design: Large-scale, population-based, prospective study. The observational data were used to emulate a target trial with 2 groups: colonoscopy screening and no screening. Setting: United States. Participants: 1 355 692 Medicare beneficiaries (2004 to 2012) aged 70 to 79 years at average risk for CRC who used Medicare preventive services and had no previous diagnostic or surveillance colonoscopies in the past 5 years. Measurements: 8-year risk for CRC and 30-day risk for adverse events. Results: In beneficiaries aged 70 to 74 years, the 8-year risk for CRC was 2.19% (95% CI, 2.00% to 2.37%) in the screening colonoscopy group and 2.62% (CI, 2.56% to 2.67%) in the no-screening group (absolute risk difference, -0.42% [CI, -0.24% to -0.63%]). Among those aged 75 to 79 years, the 8-year risk for CRC was 2.84% (CI, 2.54% to 3.13%) in the screening colonoscopy group and 2.97% (CI, 2.92% to 3.03%) in the no-screening group (risk difference, -0.14% [CI, -0.41 to 0.16]). The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1000 individuals (CI, 4.4 to 6.8) in the 70- to 74-year age group and 10.3 per 1000 (CI, 8.6 to 11.1) in the 75- to 79-year age group. Limitation: CRC-specific mortality was not available, but CRC incidence and stage were studied at diagnosis. Conclusion: Screening colonoscopy may have had a modest benefit in preventing CRC in beneficiaries aged 70 to 74 years and a smaller benefit in older beneficiaries. The risk for adverse events was low but greater among older persons. Primary Funding Source: National Institutes of Health. PMID- 27669527 TI - Salvage endoscopic ultrasound-radiologic rendezvous to re-establish biliary flow following duodenectomy with ablation of papilla. PMID- 27669526 TI - Rebound Syndrome in Multiple Sclerosis After Fingolimod Cessation-Reply. PMID- 27669528 TI - Pneumoscrotum after ERCP-related duodenal perforation. PMID- 27669529 TI - Retrieval of a migrated stent during endoscopic ultrasound-guided drainage of duodenal diverticular abscess. PMID- 27669530 TI - Multimodal endoscopic treatment of primary esophago-pleural fistula. PMID- 27669531 TI - Dysphagia due to kyphosis-induced positional changes of the carotid artery. PMID- 27669532 TI - Radiofrequency ablation of gastric antral vascular ectasia of the gastric cardia. PMID- 27669533 TI - Neuroendocrine tumor of the pancreas with cystic appearance mimicking a progressive intraductal papillary mucinous neoplasm: pitfall in medical imaging. PMID- 27669534 TI - Re-recurrence after distal gastrectomy for recurrence caused by needle tract seeding during endoscopic ultrasound-guided fine-needle aspiration of a pancreatic adenocarcinoma. PMID- 27669535 TI - Over-the-scope clipping in recurrent colonic diverticular bleeding. PMID- 27669536 TI - Use of a Roth Net Platinum Universal Retriever for the endoscopic management of a large symptomatic gallstone causing Bouveret's syndrome. PMID- 27669537 TI - Endoscopic submucosal dissection of a gastric neoplasm with osseous metaplasia. PMID- 27669538 TI - Adenomyomatous hyperplasia of the lower bile duct mimicking a papillary bile duct tumor. PMID- 27669540 TI - Improving Health and Health Care in the United States: Toward a State of Complete Well-being. PMID- 27669539 TI - Association of Nausea and Vomiting During Pregnancy With Pregnancy Loss: A Secondary Analysis of a Randomized Clinical Trial. AB - Importance: Nausea and vomiting during pregnancy have been associated with a reduced risk for pregnancy loss. However, most prior studies enrolled women with clinically recognized pregnancies, thereby missing early losses. Objective: To examine the association of nausea and vomiting during pregnancy with pregnancy loss. Design, Setting, and Participants: A randomized clinical trial, Effects of Aspirin in Gestation and Reproduction, enrolled women with 1 or 2 prior pregnancy losses at 4 US clinical centers from June 15, 2007, to July 15, 2011. This secondary analysis was limited to women with a pregnancy confirmed by positive results of a human chorionic gonadotropin (hCG) test. Nausea symptoms were ascertained from daily preconception and pregnancy diaries for gestational weeks 2 to 8. From weeks 12 to 36, participants completed monthly questionnaires summarizing symptoms for the preceding 4 weeks. A week-level variable included nausea only, nausea with vomiting, or neither. Main Outcomes and Measures: Peri implantation (hCG-detected pregnancy without ultrasonographic evidence) and clinically recognized pregnancy losses. Results: A total of 797 women (mean [SD] age, 28.7 [4.6] years) had an hCG-confirmed pregnancy. Of these, 188 pregnancies (23.6%) ended in loss. At gestational week 2, 73 of 409 women (17.8%) reported nausea without vomiting and 11 of 409 women (2.7%), nausea with vomiting. By week 8, the proportions increased to 254 of 443 women (57.3%) and 118 of 443 women (26.6%), respectively. Hazard ratios (HRs) for nausea (0.50; 95% CI, 0.32-0.80) and nausea with vomiting (0.25; 95% CI, 0.12-0.51) were inversely associated with pregnancy loss. The associations of nausea (HR, 0.59; 95% CI, 0.29-1.20) and nausea with vomiting (HR, 0.51; 95% CI, 0.11-2.25) were similar for peri implantation losses but were not statistically significant. Nausea (HR, 0.44; 95% CI, 0.26-0.74) and nausea with vomiting (HR, 0.20; 95% CI, 0.09-0.44) were associated with a reduced risk for clinical pregnancy loss. Conclusions and Relevance: Among women with 1 or 2 prior pregnancy losses, nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss. These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss. Trial Registration: clinicaltrials.gov Identifier: NCT00467363. PMID- 27669542 TI - Preface. PMID- 27669543 TI - Impact of vascular access intervention therapy on cardiac load in hemodialysis patients. AB - Vascular access intervention therapy (VAIVT) has been positioned as the first choice of treatment for stenosis lesions frequently observed in arteriovenous fistula (AVF) for hemodialysis patients in Japan. Furthermore, increased blood flow can provide a stable dialysis. In contrast, it has been reported that excess blood flow of AVF causes high-output heart failure. Although VAIVT is used to increase blood flow of AVF, the impact of VAIVT on cardiac load has been rarely reported. We examined the factors associated with cardiac load in hemodialysis patients undergoing VAIVT by measuring levels of alpha human atrial natriuretic polypeptide (hANP) and brain natriuretic peptide (BNP) before and after VAIVT. Data were extracted on hemodialysis patients who underwent measurements of alphahANP and BNP in before and after VAIVT at our facility and related facilities between February 2014 and December 2014. Nineteeen patients (median age, 73.0 [66.5-80.5] years; male, 52.6%; 36.8% with diabetes; median duration of dialysis treatment, 50.0 [21-109] months) were enrolled in this study. Flow volume of AVF was higher after VAIVT than that before VAIVT (442.0 vs. 758.0 mL/minute, P < 0.001). Moreover, resistance index (RI) of AVF after VAIVT was lower than that before VAIVT (0.61 vs. 0.53, P < 0.01). Although alphahANP did not change before and after VAIVT (55.6 vs. 54.9 pg/mL, P = 0.099), BNP after VAIVT was significantly higher than that before VAIVT (145.2 vs. 175.0 pg/mL, P < 0.05). Factors correlated with the increase in BNP were flow volume of AVF before VAIVT (r = -0.458, P = 0.049) and levels of BNP before VAIVT (r = 0.472, P = 0.041). There was no significant correlation between the increase in alphahANP with flow volume of AVF before VAIVT, levels of alphahANP before VAIVT. Patients with high levels of BNP and low flow volume of AVF before VAIVT were considered to have a high risk of developing heart failure after VAIVT. PMID- 27669541 TI - Sucrose, But Not Glucose, Blocks IL1-beta-Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway. AB - Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin-1beta (IL 1beta) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under pathological conditions. We investigated the role of autophagy activated by sucrose, a natural disaccharide, in suppressing inflammatory mediator's expression and cell death under pathological conditions in human chondrocytes. Autophagy activation was investigated by Western blotting for LC3 and Beclin-1, immunofluorescence staining for LC3 puncta, and measuring autophagic flux. Activation of mTOR, AKT, and P70S6K was evaluated by Western blotting. Chondrocyte apoptosis was evaluated by propidium iodide (PI) staining using flowcytometry, expression of Bax by Western blotting, gene expression by TaqMan assays and caspase 3/7 activity was measured using a luminescence-based assay. We found that sucrose-induced active autophagy in OA chondrocytes in vitro was dependent on the activation of AKT/mTOR/P70S6K signaling pathways but was independent of reactive oxygen species (ROS) production. Sucrose activated autophagy blocked IL-1beta-induced apoptosis and mRNA expression of MMP-13, COX-2, and IL-6 in human OA chondrocytes. Glucose or fructose, the two metabolites of sucrose, failed to induce autophagy indicating that autophagy was specifically mediated by sucrose. In conclusion, sucrose attenuated IL-1beta induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes. J. Cell. Biochem. 118: 629-639, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27669544 TI - Comparisons of amino acids, body constituents and antioxidative response between long-time HD and normal HD. AB - Introduction Oxidative stress is one of the main mediators of progression of chronic kidney diseases (CKD). Nuclear factor E2-related factor 2 (Nrf2) is the transcription factor of antioxidant and detoxifying enzymes and related proteins which play an important role in cellular defense. Long-time hemodialysis (HD) therapy (8 hours) has been considered to be more beneficial compared to normal HD therapy (4 hours). We investigated oxidative response related to Nrf2 in peripheral blood mononuclear cells (PBMCs) of long-time HD and normal HD patients. Methods Eight adult long-time HD therapy patients (44.5 +/- 3.0 years) and 10 normal HD therapy patients (68.1 +/- 2.7 years) were enrolled. PBMCs were isolated and processed for expression of Nrf2 and its related genes by qRT-PCR. Plasma indoxyl sulfate, amino acids, and body constituents were measured. Findings Plasma indoxyl sulfate was significantly low after long-time HD therapy compare to that of normal HD therapy. Although, skeletal muscle mass, lean body mass, mineral and protein were significantly decreased 2 months in normal HD patients, those in long-time HD patients were significantly increased after 2 months. Almost of amino acids were significantly decreased after HD therapy in both HD therapies. Plasma amino acids were significantly low in long-time HD patients compared to normal HD patients. In PBMCs, the expression of Nrf2 was significantly decreased and hemooxygenase-1 expression was significantly increased in long-time HD compared to normal HD. Conclusion These observations indicate the beneficial effects of in long-time HD in improving oxidative stress in patients. PMID- 27669545 TI - Reliability of delivered dialysate sodium concentration. AB - Background The results of studies investigating the effects of hyponatraemic dialysates have been mixed, with some reporting positive effects including reduction in blood pressure and inter-dialytic weight gains, whereas others have not been able to demonstrate any effect. These studies assume that setting a lower dialysate sodium results in the delivery of a hyponatraemic dialysate. We therefore measured delivered sodium to determine reliability. Methods We measured dialysate sodium in 10 BBraun Dialog+(r) and 6 Fresenius 4008H dialysis machines, which had been set up to deliver a sodium of 136 mmol/L, using flame photometry and indirect ion selective electrode (ISE) methods. Results Dialysate conductivity was 13.85 +/- 0.05 mS/cm, but dialysate sodium measured by flame photometry was 141.8 +/- 2.9 mmol/L, and 142.5 +/- 2.4 mmol/L by ISE. Both dialysis machines delivered a dialysate sodium in excess of the 136 mmol/L set, with a mean bias of 7.0 +/-2.1 mmol/L for the Dialog+(r) , and 3.7 +/- 2.6 for the 4008 with the flame photometer method, and a mean bias of 6.3 +/- 1.3 mmol/L for the Dialog+(r) , and 6.8 +/- 3.7 for the 4008 by ISE. Conclusion It is assumed when setting a dialysate sodium concentration that this sodium concentration is delivered. However we found that the dialysate sodium concentration delivered was greater than that set, despite the dialysis machines reporting a conductivity measurement in keeping with a lower sodium dialysate. Trials of lowered dialysate sodium therefore need to measure dialysate sodium concentrations to ensure what has been set is delivered. PMID- 27669546 TI - Blood pressure targets for hemodialysis patients: Aspirational or practical? AB - Whereas there is strong relationship between high blood pressure and increased overall and cardiovascular mortality for the general population, observational studies in hemodialysis patients have reported a "U" shaped relationship between pre-hemodialysis blood pressure recordings and patient survival. Previous attempts to introduce pre and post-hemodialysis blood pressure targets were associated with an increased frequency of intra-dialytic hypotension, itself an independent risk factor for mortality. Conversely, meta-analyses of trials of antihypertensive medications in hemodialysis patients, reported survival benefit for those prescribed medication. More recently, further meta-analyses have suggested a reduced risk for cardiovascular mortality benefit with a systolic blood pressures (SBPs) of less than 140 mmHg, the absolute benefit, in terms of risk reduction was greatest in those with the highest vascular disease burden. Even though data from current observational studies and studies of antihypertensive medications would suggest that patient survival would be greater with pre-dialysis SBP should be less than 160 mmHg, there is no current data to propose specific blood pressure targets. Defining blood pressure targets can only be answered by adequately powered prospective randomized controlled trials comparing different targets. As the benefits of lowering blood pressure appear to be greatest for those with most vascular disease, then blood pressure targets may have to be adjusted on an individual risk basis, and future trials should therefore stratify patients according to vascular morbidity and have different targets for patients with differing degrees of pre-existing cardiovascular disease. PMID- 27669547 TI - Role of isolated ultrafiltration in the management of chronic refractory and acute decompensated heart failure. AB - Chronic congestive heart failure (CHF) and acute decompensated heart failure (ADHF) refractory to medical therapy represent therapeutic challenges. In such patients, attempts to reduce pulmonary and systemic congestion frequently produce deterioration of renal function. In studies of patients with chronic severe CHF refractory to medical therapy (including loop diuretics), isolated ultrafiltration was frequently able to relieve congestive symptoms by precise removal of extracellular water and sodium, and in some cases was able to restore responsiveness to loop diuretics. Randomized controlled trials comparing isolated ultrafiltration and medical therapy (mainly loop diuretics) in patients with ADHF failed to demonstrate the superiority of isolated ultrafiltration over diuretic therapy with respect to renal function and mortality. Isolated ultrafiltration reduced length of hospital stay in several studies. At this time, there is insufficient evidence to support the use of isolated ultrafiltration as initial therapy of ADHF. PMID- 27669548 TI - In tandem extracorporeal therapies during hemodialysis in pediatric patients. AB - We describe the successful treatment of a pediatric transplant patient with simultaneous intermittent hemodialysis and therapeutic plasma exchange (TPE). The patient presented with kidney graft failure. He had life threatening electrolyte disturbances and fluid overload due to antibody-mediated rejection. Therefore, he was in need of both emergent kidney replacement therapy and TPE. Both extracorporeal circuits were set up, established, and maintained safely and effectively without difficulty or alarms. Running intermittent hemodialysis and TPE simultaneously significantly reduced therapy time, allowed both needed therapies priority, and provided a superior pediatric patient experience in an acute situation. PMID- 27669549 TI - Reducing blood stream infection in patients on hemodialysis: Incorporating patient engagement into a quality improvement activity. AB - Introduction Infection in our immunocompromised patients is the second leading cause of death, according to the Centers for Disease Control and Prevention (CDC). In an effort to improve quality of care, engage patients in their own care, and reduce morbidity and mortality secondary to infection, the Network designed a joint quality improvement/patient engagement activity to decrease bloodstream infection (BSI) rates. Methods Dialysis facilities were ranked utilizing 2014 National Healthcare Safety Network (NHSN) data. Selection included 20% of Network 13 facilities (n = 58) with the highest BSI rates, which captured 31% of the patient population. Findings Statistically significant (P < 0.001) improvement was reached in the reduction of BSIs; increasing patient engagement in the infection control process; and, correct completion of hand hygiene audits. Significant (P < 0.01) improvement was reached in correct completion of cannulation audits. There was also improvement in the catheter audits, but results were not significant. Discussion Involving patients in the infection control process contributed to our successful outcomes and could be replicated to meet the needs of the end stage renal disease community as a whole. PMID- 27669550 TI - Inflammatory demyelinating neuropathy heralding accelerated chediak-higashi syndrome. AB - INTRODUCTION: Chediak-Higashi syndrome (CHS) is a very rare autosomal recessive disorder (gene CHS1/LYST) characterized by partial albinism, recurrent infections, and easy bruising. Survivors develop a constellation of slowly progressive neurological manifestations. METHODS: We describe clinical, laboratory, electrophysiological, and genetic findings of a patient who developed an immune-mediated demyelinating neuropathy as the main clinical feature of CHS. RESULTS: The patient presented with subacute flaccid paraparesis, absent reflexes, and reduced vibration sense. Protein and immunoglobulins (Igs) were elevated in the cerebrospinal fluid. Electrodiagnostic tests indicated an acquired chronic demyelinating polyneuropathy. Intravenous Ig and immunosuppressant treatment resulted in neurological improvement. The patient later developed organomegaly and pancytopenia. Bone-marrow smear revealed giant azurophilic granules pathognomonic for CHS. Two novel mutations in the LYST gene were identified through whole exome sequencing [c.7786C>T and c.9106 + 1G>T]. CONCLUSIONS: This case expands the clinical phenotype of CHS and highlights inflammatory demyelinating neuropathy as a manifestation of the disease. Muscle Nerve 55: 756-760, 2017. PMID- 27669551 TI - Reply to Lago et al. Comment on "Use of Single-Well Tracer Dilution Tests to Evaluate LNAPL Flux at Seven Field Sites and Measurement of LNAPL Flux Using Single-Well Intermittent Mixing Tracer Dilution Tests". PMID- 27669553 TI - Control of the Environment in the Operating Room. AB - There is a direct relationship between the quality of the environment of a workplace and the productivity and efficiency of the work accomplished. Components such as temperature, humidity, ventilation, drafts, lighting, and noise each contribute to the quality of the overall environment and the sense of well-being of those who work there.The modern operating room is a unique workplace with specific, and frequently conflicting, environmental requirements for each of the inhabitants. Even minor disturbances in the internal environment of the operating room can have serious ramifications on the comfort, effectiveness, and safety of each of the inhabitants. A cool, well-ventilated, and dry climate is optimal for many members of the surgical team. Any significant deviation from these objectives raises the risk of decreased efficiency and productivity and adverse surgical outcomes. A warmer, more humid, and quieter environment is necessary for the patient. If these requirements are not met, the risk of surgical morbidity and mortality is increased. An important task for the surgical team is to find the correct balance between these 2 opposed requirements. Several of the components of the operating room environment, especially room temperature and airflow patterns, are easily manipulated by the members of the surgical team. In the following discussion, we will examine these elements to better understand the clinical ramifications of adjustments and accommodations that are frequently made to meet the requirements of both the surgical staff and the patient. PMID- 27669554 TI - Acute Normovolemic Hemodilution Reduces Allogeneic Red Blood Cell Transfusion in Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Trials. AB - BACKGROUND: To better understand the role of acute normovolemic hemodilution (ANH) in a surgical setting with high risk of bleeding, we analyzed all randomized controlled trials (RCTs) in the setting of cardiac surgery that compared ANH with standard intraoperative care. The aim was to assess the incidence of ANH-related number of allogeneic red blood cell units (RBCu) transfused. Secondary outcomes included the rate of allogeneic blood transfusion and estimated total blood loss. METHODS: Twenty-nine RCTs for a total of 2439 patients (1252 patients in the ANH group and 1187 in the control group) were included in our meta-analysis using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE. RESULTS: Patients in the ANH group received fewer allogeneic RBCu transfusions (mean difference = -0.79; 95% confidence interval [CI], -1.25 to -0.34; P = .001; I = 95.1%). Patients in the ANH group were overall transfused less with allogeneic blood when compared with controls (356/845 [42.1%] in the ANH group versus 491/876 [56.1%] in controls; risk ratio = 0.74; 95% CI, 0.62 to 0.87; P < .0001; I = 72.5%), and they experienced less postoperative blood loss (388 mL in ANH versus 450 mL in control; mean difference = -0.64; 95% CI, -0.97 to -0.31; P < .0001; I = 91.8%). CONCLUSIONS: ANH reduces the number of allogeneic RBCu transfused in the cardiac surgery setting together with a reduction in the rate of patients transfused with allogeneic blood and with a reduction of bleeding. PMID- 27669555 TI - Lung Ultrasonography for the Assessment of Perioperative Atelectasis: A Pilot Feasibility Study. AB - BACKGROUND: Few diagnostic tools are available to anesthesiologists when confronted with intraoperative hypoxemia. Lung ultrasonography is a safe and accurate bedside imaging modality. The aim of this study was to evaluate the feasibility of lung ultrasonography during the perioperative period and assess its ability to detect intraoperative respiratory complications and oxygenation changes resulting from perioperative atelectasis. METHODS: In this prospective observational pilot study, 30 consecutive patients scheduled for laparoscopic surgery were recruited. Mechanical ventilation was standardized. Lung ultrasonography was performed at 5 predefined time points: before induction of general anesthesia (GA), after induction of GA, after pneumoperitoneum insufflation, on arrival in the recovery room, and before recovery room discharge. For each echographic examination, 12 pulmonary quadrants were imaged. From these, a semiquantitative score, the lung ultrasound (LUS) score, was calculated to assess lung aeration at each time point. RESULTS: Lung ultrasonography was possible in all patients. Changes in the LUS score between the postinduction period and arrival in the recovery room were correlated with changes in oxygenation (Spearman r = -0.43, P = .018). Induction of GA was associated with an increase in the LUS score, which gradually worsened at all time points until recovery room discharge. This increase was significantly worse in the basal and dependent lung zones. Lung ultrasonography helped in the detection of 2 capnothoraces, 1 endobronchial intubation, and 1 episode of subclinical pulmonary edema. CONCLUSIONS: Lung ultrasonography in the perioperative period is feasible, allows tracking of perioperative atelectasis, and facilitates the diagnosis of respiratory complications. The evolution of aeration loss correlates moderately with changes in oxygenation. PMID- 27669556 TI - Metformin Synergizes With Conventional and Adjuvant Analgesic Drugs to Reduce Inflammatory Hyperalgesia in Rats. AB - BACKGROUND: Metformin is a widely used and safe antidiabetic drug that has recently been shown to possess analgesic properties in models of inflammatory pain. Because various arthritic inflammatory disorders are highly prevalent in diabetic patients, we aimed to examine the type of interaction between metformin and several conventional and adjuvant analgesic drugs (ibuprofen, aspirin, tramadol, and pregabalin) in a rat model of somatic inflammatory hyperalgesia. METHODS: Inflammation of the rat hind paw was induced by an intraplantar injection of carrageenan (0.1 mL, 1%). The antihyperalgesic effects of metformin (intraperitoneally), analgesics (orally or intraperitoneally), and 2-drug metformin-analgesic combinations were assessed with an electronic Von Frey anesthesiometer, by measuring the change in paw withdrawal thresholds induced by carrageenan (n = 6 rats in drug/drug combination-treated groups). First, we determined the doses of individual drugs needed to produce an antihyperalgesic effect of 50% (ED50 values). In combination experiments, drugs were coadministered in fixed-dose fractions (1/16, 1/8, 1/4, and 1/2) of their individual ED50 values and the type of interaction between components was determined by isobolographic analysis. RESULTS: Metformin (50-200 mg/kg) significantly and dose-dependently reduced carrageenan-induced hyperalgesia with a maximal antihyperalgesic effect (mean +/- SEM) of 62 +/- 6% (all P <= .024). Ibuprofen (25-150 mg/kg), aspirin (100-400 mg/kg), tramadol (0.5-5 mg/kg), and pregabalin (2.5-20 mg/kg) also produced significant and dose-dependent antihyperalgesic effects (all P <= .042) of similar magnitude to metformin (the maximal antihyperalgesic effects were 73 +/- 4% for ibuprofen, 62 +/- 4.2% for aspirin, 69 +/- 5.9% for tramadol, and 56 +/- 3.9% for pregabalin). In combination experiments, administration of 2-drug metformin-analgesic combinations led to a significant and dose-dependent reduction of carrageenan induced hyperalgesia (all P <= .027). The isobolographic analysis revealed that metformin interacted synergistically with the examined analgesics (experimental ED50 values of 2-drug combinations were significantly lower than theoretical additive ED50 values; all P < .05) and that there was a similar, approximately 5 fold, reduction of doses of both drugs in all tested combinations. CONCLUSIONS: Our results suggest that in patients who are already receiving metformin therapy, lower doses of ibuprofen/aspirin/tramadol/pregabalin might be sufficient for achieving satisfactory pain relief. Metformin-aspirin combination might be particularly useful because it may achieve multiple therapeutic goals (glucoregulation, pain relief, and cardioprotection). PMID- 27669557 TI - Preprocedure Ultrasonography Before Initiating a Neuraxial Anesthetic Procedure. PMID- 27669558 TI - The Three Laws of Autonomous and Closed-Loop Systems in Anesthesia. PMID- 27669564 TI - The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012. AB - INTRODUCTION: Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. METHODS: We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV infected populations and used Poisson regression to determine if trends were significant. RESULTS: We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. CONCLUSIONS: In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced tuberculosis control programme and routine childhood immunisation with pneumococcal conjugate vaccines. PMID- 27669565 TI - Suppression of Very Early Stage Of Adipogenesis by Baicalein, a Plant-Derived Flavonoid through Reduced Akt-C/EBPalpha-GLUT4 Signaling-Mediated Glucose Uptake in 3T3-L1 Adipocytes. AB - Baicalein has been used as a Chinese medicine, and is an abundant plant flavonoid present in fruits and vegetables. Here, we examined the effects of baicalein in adipogenesis and investigated its molecular mechanism in adipocytes. Baicalein lowered the intracellular lipid accumulation and decreased the transcription levels of the adipocyte-specific genes in mouse 3T3-L1 adipocytes. Glucose uptake mediated by glucose transporter 4 (GLUT4) was reduced, causing down-regulation of the intracellular lipid accumulation. These reductions were also observed even when baicalein was added in only early stage of adipogenesis (0-2 days) of 6-day adipogenesis. Chromatin immunoprecipitation assay showed that baicalein decreased the binding level of C/EBPalpha protein to the promoter region of the GLUT4 gene. Phosphorylation of Akt at 1 h after the initiation of adipogenesis was inhibited by the treatment with baicalein. Inhibition during only the first 1.5 h after the initiation of adipogenesis by baicalein or an Akt inhibitor was enough to decrease the lipid contents in the cells undergoing adipocyte differentiation for 6 days. These results indicate that baicalein decreased the intracellular lipid accumulation by down-regulation of glucose uptake via repression of Akt C/EBPalpha-GLUT4 signaling in the very early stage of adipogenesis of 3T3-L1 adipocytes. PMID- 27669566 TI - Critical Involvement of Environmental Carbon Dioxide Fixation to Drive Wax Ester Fermentation in Euglena. AB - Accumulation profiles of wax esters in Euglena gracilis Z were studied under several environmental conditions. The highest amount of total wax esters accumulated under hypoxia in the dark, and C28 (myristyl-myristate, C14:0-C14:0) was prevalent among all conditions investigated. The wax ester production was almost completely suppressed under anoxia in the light, and supplying exogenous inorganic carbon sources restored wax ester fermentation, indicating the need for external carbon sources for the wax ester fermentation. 13C-labeling experiments revealed specific isotopic enrichment in the odd-numbered fatty acids derived from wax esters, indicating that the exogenously-supplied CO2 was incorporated into wax esters via the propionyl-CoA pathway through the reverse tricarboxylic acid (TCA) cycle. The addition of 3-mercaptopicolinic acid, a phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, significantly affected the incorporation of 13C into citrate and malate as the biosynthetic intermediates of the odd-numbered fatty acids, suggesting the involvement of PEPCK reaction to drive wax ester fermentation. Additionally, the 13C-enrichment pattern of succinate suggested that the CO2 assimilation might proceed through alternative pathways in addition to the PEPCK reaction. The current results indicate that the mechanisms of anoxic CO2 assimilation are an important target to reinforce wax ester fermentation in Euglena. PMID- 27669567 TI - PFK15, a Small Molecule Inhibitor of PFKFB3, Induces Cell Cycle Arrest, Apoptosis and Inhibits Invasion in Gastric Cancer. AB - PFKFB3 (6-phosphofructo-2-kinase) synthesizes fructose 2,6-bisphosphate (F2,6P2), which is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1), the rate limiting enzyme of glycolysis. Overexpression of the PFKFB3 enzyme leads to high glycolytic metabolism, which is required for cancer cells to survive in the harsh tumor microenvironment. The objective of this study was to investigate the antitumor activity of PFK15 (1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one), a small molecule inhibitor of PFKFB3, against gastric cancer and to explore its potential mechanisms. The effects of PFK15 on proliferation, apoptosis and cell cycle progression in gastric cancer cells were evaluated by cytotoxicity and apoptosis assays, flow cytometry, and western blotting. In addition, the invasion inhibition effects of PFK15 were measured by transwell invasion assay and western blot analysis, and a xenograft tumor model was used to verify the therapeutic effect of PFK15 in vivo. Results showed that PFK15 inhibited the proliferation, caused cell cycle arrest in G0/G1 phase by blocking the Cyclin-CDKs/Rb/E2F signaling pathway, and induced apoptosis through mitochondria in gastric cancer cells. Tumor volume and weight were also significantly reduced upon intraperitoneal injection with PFK15 at 25 mg/kg. In addition, PFK15 inhibited the invasion of gastric cancer cells by downregulating focal adhesion kinase (FAK) expression and upregulating E-cadherin expression. Taken together, our findings indicate that PFK15 is a promising anticancer drug for treating gastric cancer. PMID- 27669568 TI - The Effect of Spatial and Temporal Resolution of Cine Phase Contrast MRI on Wall Shear Stress and Oscillatory Shear Index Assessment. AB - INTRODUCTION: Wall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom. METHODS: A carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions. RESULTS: The mean PC-MRI CCA flow (2.5+/-0.2mL/s) agreed with the ultrasound probe measurements (2.7+/-0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA: 24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI). CONCLUSION: We show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution. PMID- 27669570 TI - Phlorofucofuroeckol Improves Glutamate-Induced Neurotoxicity through Modulation of Oxidative Stress-Mediated Mitochondrial Dysfunction in PC12 Cells. AB - Stroke is a complex neurodegenerative disorder with a clinically high prevalence and mortality. Despite many efforts to protect against ischemic stroke, its incidence and related permanent disabilities continue to increase. In this study, we found that pretreatment with phlorofucofuroeckol (PFF), isolated from brown algae species, significantly increased cell viability in glutamate-stimulated PC12 cells. Additionally, glutamate-stimulated cells showed irregular morphology, but PFF pretreatment resulted in improved cell morphology, which resembled that in cells cultured under normal conditions. We further showed that PFF pretreatment effectively inhibited glutamate-induced apoptotic cell death in a caspase-dependent manner. Reactive oxygen species (ROS) induced by oxidative stress are closely associated with ischemia-induced neurological diseases. Exposure of PC12 cells to glutamate induced abundant production of intracellular ROS and mitochondrial dysfunction, which was attenuated by PFF in a dose dependent manner. In vivo studies revealed that PFF-mediated prevention was achieved predominantly through inhibition of apoptosis and mitochondrial ROS generation. Taken together, these results suggest the possibility of PFF as a neuroprotective agent in ischemic stroke. PMID- 27669571 TI - Left Ventricular Function Evaluation on a 3T MR Scanner with Parallel RF Transmission Technique: Prospective Comparison of Cine Sequences Acquired before and after Gadolinium Injection. AB - OBJECTIVES: To compare cine MR b-TFE sequences acquired before and after gadolinium injection, on a 3T scanner with a parallel RF transmission technique in order to potentially improve scanning time efficiency when evaluating LV function. METHODS: 25 consecutive patients scheduled for a cardiac MRI were prospectively included and had their b-TFE cine sequences acquired before and right after gadobutrol injection. Images were assessed qualitatively (overall image quality, LV edge sharpness, artifacts and LV wall motion) and quantitatively with measurement of LVEF, LV mass, and telediastolic volume and contrast-to-noise ratio (CNR) between the myocardium and the cardiac chamber. Statistical analysis was conducted using a Bayesian paradigm. RESULTS: No difference was found before or after injection for the LVEF, LV mass and telediastolic volume evaluations. Overall image quality and CNR were significantly lower after injection (estimated coefficient cine after > cine before gadolinium: -1.75 CI = [-3.78;-0.0305], prob(coef>0) = 0% and -0.23 CI = [ 0.49;0.04], prob(coef>0) = 4%) respectively), but this decrease did not affect the visual assessment of LV wall motion (cine after > cine before gadolinium: 1.46 CI = [-4.72;1.13], prob(coef>0) = 15%). CONCLUSIONS: In 3T cardiac MRI acquired with parallel RF transmission technique, qualitative and quantitative assessment of LV function can reliably be performed with cine sequences acquired after gadolinium injection, despite a significant decrease in the CNR and the overall image quality. PMID- 27669569 TI - Diversification of Angraecum (Orchidaceae, Vandeae) in Madagascar: Revised Phylogeny Reveals Species Accumulation through Time Rather than Rapid Radiation. AB - Angraecum is the largest genus of subtribe Angraecinae (Orchidaceae) with about 221 species. Madagascar is the center of the diversity for the genus with ca. 142 species, of which 90% are endemic. The great morphological diversity associated with species diversification in the genus on the island of Madagascar offers valuable insights for macroevolutionary studies. Phylogenies of the Angraecinae have been published but a lack of taxon and character sampling and their limited taxonomic resolution limit their uses for macroevolutionary studies. We present a new phylogeny of Angraecum based on chloroplast sequence data (matk, rps16, trnL), nuclear ribosomal (ITS2) and 39 morphological characters from 194 Angraecinae species of which 69 were newly sampled. Using this phylogeny, we evaluated the monophyly of the sections of Angraecum as defined by Garay and investigated the patterns of species diversification within the genus. We used maximum parsimony and bayesian analyses to generate phylogenetic trees and dated divergence times of the phylogeny. We analyzed diversification patterns within Angraecinae and Angraecum with an emphasis on four floral characters (flower color, flower size, labellum position, spur length) using macroevolutionary models to evaluate which characters or character states are associated with speciation rates, and inferred ancestral states of these characters. The phylogenetic analysis showed the polyphyly of Angraecum sensu lato and of all Angraecum sections except sect. Hadrangis, and that morphology can be consistent with the phylogeny. It appeared that the characters (flower color, flower size, spur length) formerly used by many authors to delineate Angraecum groups were insufficient to do so. However, the newly described character, position of the labellum (uppermost and lowermost), was the main character delimiting clades within a monophyletic Angraecum sensu stricto. This character also appeared to be associated with speciation rates in Angraecum. The macroevolutionary model-based phylogeny failed to detect shifts in diversification that could be associated directly with morphological diversification. Diversification in Angraecum resulted from gradual species accumulation through time rather than from rapid radiation, a diversification pattern often encountered in tropical rain forests. PMID- 27669572 TI - Venous Thromboembolism in Primary Nephrotic Syndrome - Is the Risk High Enough to Justify Prophylactic Anticoagulation? AB - BACKGROUND: The reported incidence of venous thromboembolism (VTE) in patients with nephrotic syndrome (NS) varies widely, as does the approach to prophylactic anticoagulation. We aimed to assess the incidence of VTE in patients with primary NS in order to inform a sample size calculation to determine if a future clinical trial will ever be feasible. METHODS: All adults undergoing native renal biopsy for NS between 2008 and 2013 yielding a diagnosis of primary glomerulonephritis were identified. Baseline serum albumin, urine protein:creatinine ratio, estimated glomerular filtration rate, date of biopsy and histological diagnosis were recorded. Episodes of objectively verified VTE were identified using the electronic patient record. Sample size calculations were performed based on 2 independent samples with a dichotomous outcome and to achieve a power of 80% and p < 0.05. RESULTS: Two hundred six patients were included of which 60% were male and mean age at biopsy was 55 years (SD 19). Median follow-up was 2.9 years (interquartile range (IQR) 1.6-4.7). Fourteen (6.8%) patients suffered VTE. Median time to diagnosis of VTE from renal biopsy was 36 days (IQR -22 to 178), with 6 VTEs occurring prior to biopsy and 1 during remission. In a total of 270 patient years of NS, there were 7 VTE that could potentially have been avoided if anticoagulation was given for the duration of NS, that is, 2.6% risk per year of NS; this risk was highest for patients with minimal change nephropathy at 13.3% per year of NS, compared to 0.65% per year of NS for those with idiopathic membranous nephropathy. Assuming a 75% reduction in the incidence of VTE with prophylactic anticoagulation, 972 participants would be required for a future clinical trial to have 80% power. CONCLUSIONS: Patients with primary NS are at an increased risk of VTE. The timing of VTE means that only half of episodes would be targeted by prophylactic anticoagulation. Given the low frequency of events, a well-powered clinical trial would be challenging to achieve. PMID- 27669573 TI - Premenstrual syndrome health-related quality of life and psychiatric comorbidity in a clinical adolescent sample: a cross-sectional study. AB - OBJECTIVE: Adolescents who were admitted to the child and adolescent psychiatry clinic were compared with respect to the premenstrual symptom severity, psychiatric comorbidities and health related quality of life (HRQoL). METHODS: The research group was identified using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Premenstrual Assessment Form. They completed the Pediatric Quality of Life Inventory (The PedsQL). RESULTS: There were 55 adolescents who were eligible for the study and 89% of participants were diagnosed with at least one psychiatric disorder. The most common psychiatric diagnoses among the diagnosed cases were anxiety and major depressive disorders. Of all of the cases, 78.2% were diagnosed with premenstrual syndrome (PMS) and among those cases, 46.5% had mild, 34.8% had moderate and 18.6% had severe PMS. Most common PMS symptom was anger/irritability. HRQoL in the group with PMS was significantly lower than that of the adolescents without PMS. Moreover, HRQoL of adolescents with PMS was found to deteriorate with the increasing severity of PMS. CONCLUSIONS: This study is of great importance since it demonstrated that PMS frequency is very high in a clinical adolescent population and negatively affects their HRQoL as similar to non-clinical adolescent population studies. PMID- 27669575 TI - Editorial. AB - During the mid 1980s, the enterprising Burford Nurse Development Unit (NDU) established a nursing beds pilot. It was widely acclaimed and for a while it captivated the profession. Oxford followed suit and what had become an interesting experiment took on a new significance. It seemed we could be witnessing the start of a whole new approach to nursing care in acute hospital settings. But inexplicably the interest faded, enthusiasm waned and the unit closed in 1989, despite some positive outcomes of the unit's evaluation. It could be that like so many innovations in nursing, the success of nursing beds would survive and thrive - provided the right mix of personalities remained to drive them forward. Remove the innovators and the innovation slowly dies. PMID- 27669574 TI - Binding Site Geometry and Subdomain Valency Control Effects of Neutralizing Lectins on HIV-1 Viral Particles. AB - Carbohydrate binding proteins such as griffithsin, cyanovirin-N, and BanLec are potent HIV entry inhibitors and promising microbicides. Each binds to high mannose glycans on the surface envelope glycoprotein gp120, yet the mechanisms by which they engage viral spikes and exhibit inhibition constants ranging from nanomolar to picomolar are not understood. To determine the structural and mechanistic basis for recognition and potency, we selected a panel of lectins possessing different valencies per subunit, oligomeric states, and relative orientations of carbohydrate binding sites to systematically probe their contributions to inhibiting viral entry. Cryo-electron micrographs and immuno gold staining of lectin-treated viral particles revealed two distinct effects namely, viral aggregation or clustering of the HIV-1 envelope on the viral membrane-that were dictated by carbohydrate binding site geometry and valency. "Sandwich" surface plasmon resonance experiments revealed that a second binding event occurs only for those lectins that could aggregate viral particles. Furthermore, picomolar Kd values were observed for the second binding event, providing a mechanism by which picomolar IC50 values are achieved. We suggest that these binding and aggregation phenomena translate to neutralization potency. PMID- 27669577 TI - Trevor Clay has lung transplant. AB - Trevor Clay, former RCN General Secretary underwent a lung transplant at Harefield Hospital last week. His condition is said to be stable. He was transferred from the Royal Brompton where he had been for a number of weeks due to a deterioration in his condition caused by emphysema. PMID- 27669576 TI - New regional posts. AB - The new regional chief executives were due to be announced this week. The line up was expected to be; Chris Spry, S Thames; Ron Kerr, N Thames; Brian Edwards, West Midlands; Barbara Stocking, East Anglian and Oxford; Liam Donaldson North East and Yorkshire; Robert Tinston, North West and Keith McLean, Trent. No appointment was made in South West, with Pamela Charlwood, Alasdair Liddell, Bryan Harrison and Kevin Woods not among the appointments. Ken Jarrold was tipped to be the new ME Director of Human Resources. PMID- 27669578 TI - Mental Health Review gets a cool reception. AB - The long-awaited report into the future of mental health nursing was published last week amid fears it will be left to gather dust on the shelves of the health department. PMID- 27669579 TI - PREP plans likely to prove disappointing. AB - The Government is set to unveil its plans for PREP funding at the RCN Congress in Bournemouth next month but nurses are expected to be bitterly disappointed at the plans which will fall far short of expectations. PMID- 27669580 TI - Survey shows NHS workload hampers child protection. AB - Many 'designated nurses' are being prevented from providing the quality of child protection work outlined in the Children Act, an RCN survey has revealed. PMID- 27669582 TI - Plea for caution on prescribing. AB - An influential community nursing academic has issued 'a plea for caution' on nurse prescribing. PMID- 27669581 TI - Greenwich takes the rap for lost' patient. AB - An internal enquiry at the hospital where a woman died after being 'lost' has slammed management for what it described as 'indifferent medical leadership'. PMID- 27669583 TI - Link-making trip from the Highlands. AB - Staff nurse Mary Cullen, centre, from Raigmore Hospital in Inverness, recently spent a week at the regional paediatric oncology unit in Glasgow's Royal Hospital for Sick Children. The trip was part of a Malcolm Sargent Cancer Fund for Children initiative to help children suffering from cancer in the Highlands. It gave Ms Cullen the opportunity to forge links with the doctors and nurses who work with her patients when they travel to Glasgow for specialist treatment. PMID- 27669584 TI - Nursing unit relieves pressure. AB - Direct referrals may be the next stage in the development of a successful nursing led in-patient unit set up to take the pressure off acute services at a busy central London hospital, Department of Health Chief Nursing Officer Yvonne Moores said this week. PMID- 27669585 TI - Low standards in Northern Ireland? AB - The Northern Ireland health and social services department should carry out an investigation to discover why health care standards are so low in the province, an all-party committee of MPs has said. PMID- 27669586 TI - Row over Derby trust claims. AB - A fresh row between unions and a Derby trust broke out last week after trust managers issued a press release claiming success in their efforts to introduce new grading structures and performance-related pay for nurses. PMID- 27669588 TI - Unions move in dispute. AB - Nursing unions have threatened court action against Park- side Health if latest moves to settle a dispute over 70 redundancies fail. PMID- 27669587 TI - Unions criticise redundancy goal. AB - The RCN has slammed a West Midlands health authority for giving unions just days to respond to plans to axe 1,200 staff by the autumn. PMID- 27669589 TI - Nurses ignored in report on drugs. AB - The Royal College of Nursing has attacked an Audit Commission study of the NHS drugs bill for failing to acknowledge the impact of nurses on doctors' prescribing. PMID- 27669590 TI - Parliament. AB - * Moves by a Merseyside health trust to axe the number of school nurses by up to half have come under fire in the Commons. Labour MPs are furious over proposals by St Helens and Knowsley Community Health Trust to slash L80,000 from its school nurse budget. The decision threatens to reduce the number of posts by up to 16 from a total of 34. Knowsley North Labour member George Howarth says the trust must think again and reverse its proposals. PMID- 27669591 TI - ? AB - The devolution of power to health service trusts stands in the way of improving MIS efficiency, Professor Sir Douglas Black said this week. Delivering the first Office of Health Economics lecture, Sir Douglas argued that a more coherent' system is needed so that innovations can be tried . on a large scale. PMID- 27669592 TI - Improved benefits still not enough. AB - The Government has been accused of not going far enough in extending maternity benefits and rights for women. PMID- 27669594 TI - Mothers support midwives. AB - Mothers supporting two midwives disciplined for allowing a woman to give birth in a waterpool at home delivered a petition to the health department last week. PMID- 27669595 TI - Staffing levels crucial after Allitt report. AB - The Royal College of Nursing's General Secretary Christine Hancock has told nurses to insist on proper ward staffing levels following the findings of the Clothier Report on the Beverly Allitt murders. PMID- 27669596 TI - 'Do as you would be done by' is the theme for nurses. AB - Treat others as you would want to be treated yourself is the concept behind the named nurse initiative, the Chief Executive of the NHS in Scotland said last week. PMID- 27669597 TI - Managers blamed for failure of nursing computer systems. AB - Nursing computer information management systems are failing in many areas because managers have not set out clear aims and objectives for their use, an independent study claims. PMID- 27669598 TI - Satellite teleconference will consider why anti-smoking measures do not help the poor. AB - A nationwide satellite teleconference for health professionals is to be held in May to discuss the implications of a report published this week which shows that anti-smoking campaigns have failed to reach people on lower incomes. PMID- 27669599 TI - Mind calls for women's right to choose single-sex wards. AB - Mentally ill women should never be forced to stay in mixed sex wards and must have the right to choose the gender of their key worker, the mental health charity Mind demanded last week. PMID- 27669600 TI - Give us back our civil rights service user tells conference. AB - Women lose many of their civil rights on admission to mental health units, a service user told the Mind conference. The conference in National Depression Week coincided with International Women's Day. PMID- 27669602 TI - ? PMID- 27669601 TI - Health visitors link with royal colleges. AB - The Health Visitors' Association last week joined forces with the Royal College of Psychiatrists and the Royal College of General Practitioners to promote awareness of post-natal depression. PMID- 27669603 TI - Public interest test proposal on NHS trust mergers. AB - A public interest test should be completed by nurses and carers to reveal their attitudes to NHS trust mergers, a report has said. PMID- 27669605 TI - BBC stonewalled in search for opinions. AB - By Simon Canning A BBC documentary maker has struck a wall of silence trying to find nurses willing to speak on record about the ethics of resuscitation practices. PMID- 27669604 TI - World news. AB - Europe Nurses across Europe are suffering from overwork and stress, with auxiliaries most hard pressed, a report from the European Parliament women's rights committee claims. PMID- 27669606 TI - Nurses need training for pressure sore mattresses. AB - The benefits of a new mattress aimed at helping to prevent pressure sores will only be fully realised if nurses receive careful and detailed education, a study by Dutch researchers claims. PMID- 27669607 TI - Public awareness of diabetes boosted by poster campaign. AB - A high profile advertising campaign on diabetes had a marked effect on public awareness without increasing fear or anxiety about the condition, a study on the programme's impact has found. PMID- 27669608 TI - Homeless people to get TB screening in London. AB - Levels of tuberculosis similar to those in developing countries and New York have been found among homeless people in London, the charity Crisis said this week. PMID- 27669609 TI - Treat mini peak flow readings with caution. AB - Mini peak flow meters may not accurately track clinically important changes in the lung function of children with asthma, researchers say. PMID- 27669610 TI - Eradication therapy in duodenal ulcer. AB - A one-week course of treatment to eradicate Helicobacter pylori heals duodenal ulceration in most infected patients without the need for anti-acid drugs, researchers from Hong Kong say. PMID- 27669611 TI - Benefits of osteopathy in general practice. AB - Osteopathy can reduce the number of GP consultations and the number of days of prescribed medication, according to a team of researchers in London. PMID- 27669612 TI - Scope for improvement in primary care. AB - Although primary care has an important role in the prevention and management of HIV, there is considerable scope for improvement in the acceptability of general practice to homosexual men. PMID- 27669613 TI - Fishing in murky waters. AB - Like the Loch Ness Monster, funding for PREP swims huge, but unseen within the pool of the health department budget. Some say they have seen the beast with their own eyes. Others deny it as a fairy tale, carefully spun to make nurses feel more at ease with their educational futures. As with Nessie, the money, they ; fear, does not exist. PMID- 27669614 TI - Women not men need group boost. AB - As a feminist I would support Mark Crump's call for a 'men's issues group'(Fed up with feminism - withered by women, Letters, February 23) - if men were concentrated in the lower grades in nursing; if men were forced to lose grade after having children; if men were hampered from achieving their full potential because of poor maternity leave provision, inflexible working patterns and inadequate child care facilities. PMID- 27669615 TI - More on familiarity and contempt. AB - I was pleased to read the article on addressing patients by first names (Names hurt, Viewpoint, February 23). PMID- 27669616 TI - Jumping off without a parachute? AB - At last - the debate begins. I very much enjoyed Annie Chellel's article, Divide and cruel (Viewpoint, March 2). PMID- 27669617 TI - Video could have nasty consequences. AB - I am a registered nurse and am therefore not easily shocked by the physical aspects of care, whether dealing with venous ulcers, amputations and so on. I was, however, greatly concerned by the inclusion of a little girl in the television component of the RCN Nursing Update learning unit on promoting continence. PMID- 27669618 TI - Annie Entwistle. AB - Annie Entwistle (known as Twizzy), a remarkable woman who dedicated her life to nursing, died last November at the age of 83. Until her retirement in 1970, she was senior tutor at Salford Royal Hospital. Miss Entwistle was held in affection and high regard by all who knew her, and she promoted a philosophy of care which was years ahead of the times. PMID- 27669619 TI - A breath of fresh air from the past. AB - Before the advent of steroids, there was very little relief for asthma and eczema sufferers, but what was to play a large part in their recovery, and that of many others with debilitating illnesses, was attendance at an open-air school. PMID- 27669620 TI - Causes of concern in nursing homes. AB - I think the reasons for the upsurge in complaints about nurses in nursing homes (UKCC warns of 'immense' crisis in nursing home sector, News, February 23) are threefold: the increase in the number of homes; the fact that we now deal with social workers more, who have a different philosophy of care; and the fact that we are inspected at least twice a year by health board inspection teams. PMID- 27669621 TI - Reunions. AB - * Forty years on, I would like to arrange a reunion of all September 1954 PTS nurses from The Royal Berkshire Hospital. Please contact: Iris Alsop (nee Robins) 21 Vernon Road Poynton Cheshire SK12 1LP. PMID- 27669622 TI - Information exchange. AB - *We are beginning a project to identify areas of stress for staff working in a busy cardiology unit. If any specialist units have explored this area or successfully implemented a similar scheme, we would be most grateful for any help or advice. PMID- 27669623 TI - Delusions and Hallucinations in Old Age C Katona Delusions and Hallucinations in Old Age and R Levy , editors Gaskell 240pp L12.50 0-902241-47-8. AB - Although the last few years saw a whole range of new books available about old age psychiatry and caring for dementia sufferers, Delusions and Hallucinations in Old Age offers something new. PMID- 27669624 TI - Colour guide of holistic oral care J Griffiths Colour guide of holistic oral care Boyle S Mosby-Year Book Europe 266pp L14.95 0-7234-1779-2. AB - The Colour Guide of Holistic Oral Care: A Practical Approach provides a helpful and practical reference text which, although 'primarily written for nurses', could be utilised by a wide cross-section of professionals. PMID- 27669625 TI - The professional nurse: issues and actions The professional nurse: issues and actions A B Grant Springhouse 470pp L18.50 0-87434-504-9 [Formula: see text]. AB - According to Colleen Ehrenberg's Foreword The Professional Nurse: Issues and Actions contains 'the content identified as necessary for socialisation into professionalnursing'. This content isarranged in 12 chapters, covering a wide range ofsubjects. PMID- 27669626 TI - International. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Blood-worth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA 1 2AX. Fax: 081-423 3861. PMID- 27669627 TI - Dynamics of the Orientational Factor in Fluorescence Resonance Energy Transfer. AB - A one-dimensional diffusion equation is derived for the time evolution of the orientational factor, kappa2, in the Forster energy transfer rate. The kappa2 dependent diffusion coefficient is obtained in three different ways: (1) by requiring the kappa2 autocorrelation function, calculated using the kappa2 diffusion equation, to be single-exponential with the exact characteristic time; (2) by projecting the multidimensional diffusion equation for the transition dipoles onto kappa2 using the local equilibrium approximation; and (3) by requiring exact and approximate kappa2 trajectories to be as close as possible using a Bayesian approach. Within the framework of this simple theory, the distance dependence of the fluorescence resonance energy transfer (FRET) efficiency can be calculated for all values of the ratio of the rotational correlation time of the transition dipoles to the lifetime of the donor excited state. The theoretical predictions are compared to the exact values obtained from Brownian dynamics simulations of the reorientation of the donor and acceptor transition dipoles. PMID- 27669628 TI - Screening methods for post-stroke visual impairment: a systematic review. AB - PURPOSE: To provide a systematic overview of the various tools available to screen for post-stroke visual impairment. METHODS: A review of the literature was conducted including randomised controlled trials, controlled trials, cohort studies, observational studies, systematic reviews and retrospective medical note reviews. All languages were included and translation was obtained. Participants included adults >=18 years old diagnosed with a visual impairment as a direct cause of a stroke. We searched a broad range of scholarly online resources and hand-searched articles registers of published, unpublished and on-going trials. Search terms included a variety of MESH terms and alternatives in relation to stroke and visual conditions. Study selection was performed by two authors independently. The quality of the evidence and risk of bias were assessed using the STROBE, GRACE and PRISMA statements. RESULTS: A total of 25 articles (n = 2924) were included in this review. Articles appraised reported on tools screening solely for visual impairments or for general post-stroke disabilities inclusive of vision. The majority of identified tools screen for visual perception including visual neglect (VN), with few screening for visual acuity (VA), visual field (VF) loss or ocular motility (OM) defects. Six articles reported on nine screening tools which combined visual screening assessment alongside screening for general stroke disabilities. Of these, three included screening for VA; three screened for VF loss; three screened for OM defects and all screened for VN. Two tools screened for all visual impairments. A further 19 articles were found which reported on individual vision screening tests in stroke populations; two for VF loss; 11 for VN and six for other visual perceptual defects. Most tools cannot accurately account for those with aphasia or communicative deficits, which are common problems following a stroke. CONCLUSION: There is currently no standardised visual screening tool which can accurately assess all potential post-stroke visual impairments. The current tools screen for only a number of potential stroke-related impairments, which means many visual defects may be missed. The sensitivity of those which screen for all impairments is significantly lowered when patients are unable to report their visual symptoms. Future research is required to develop a tool capable of assessing stroke patients which encompasses all potential visual deficits and can also be easily performed by both the patients and administered by health care professionals in order to ensure all stroke survivors with visual impairment are accurately identified and managed. Implications for Rehabilitation Over 65% of stroke survivors will suffer from a visual impairment, whereas 45% of stroke units do not assess vision. Visual impairment significantly reduces the quality of life, such as being unable to return to work, driving and depression. This review outlines the available screening methods to accurately identify stroke survivors with visual impairments. Identifying visual impairment after stroke can aid general rehabilitation and thus, improve the quality of life for these patients. PMID- 27669629 TI - Randomized controlled trials are needed to test videothoracoscopy versus thoracotomy for lung cancer lobectomy. AB - 3rd Mediterranean Symposium on Thoracic Surgical Oncology, Catania, Italy, 21-22 April 2016 Surgeons presented their experience on videothoracoscopic lobectomy at the 3rd Mediterranean Symposium on Thoracic Surgical Oncology. The audience did not question that lobectomy could be done safely and as completely by videothoracoscopic techniques provided it was in expert and practiced hands and suitable patients. The question addressed here is whether video-assisted thoracic surgery can replace thoracotomy as a standard of care in patients suitable for either approach. To determine which provides the better outcome in terms of long term survival with equivalent quality of life, would require direct comparison in pragmatic randomized controlled trials. PMID- 27669630 TI - Preventing Biomolecular Adsorption in Electrowetting-Based Biofluidic Chips. AB - Electrowetting-on-dielectric (EWOD) is a new method for moving liquids in biofluidic chips through electrical modification of the surface hydrophobicity. EWOD-based devices are reconfigurable, have low power requirements, and can handle neutral and charged analytes, as well as particulates. We show that biomolecular adsorption in EWOD is minimized by limiting the time during which no potential is applied and through choice of solution pH and electrode polarity. The same approach may be useful for controlling biomolecular adsorption in other applications of hydrophobic dielectric materials. These results demonstrate the feasibility of implementing EWOD for fluid actuation in biofluidic chips. PMID- 27669631 TI - Th1, Th17, CXCL16 and homocysteine elevated after intracranial and cervical stent implantation. AB - The presence of Th1 and Th17 cells has been observed as major inducers in inflammation and immune responses associated stenting. However, there is rare data on the impact of Th1, Th17, CXCL16 and homocysteine after cerebral stent implantation. Here, we performed the statistical analysis to first evaluate the variation of the Th17and Th1 cells and their related cytokines, CXCL16 and homocysteine in the peripheral blood of patients with cerebral stenting. The flow cytometry was used to detect the proportion of Th1 and Th17 cells in peripheral blood mononuclear cells (PBMCs). The enzyme-linked immunosorbent assay was used to measure the serum concentrations of IFN-gamma, IL-17 and CXCL16. Plasma homocysteine was examined by immunoturbidimetry. The level of Th1, CXCL16 and homocysteine showed an increase at 3 d, followed by the continuous decrease at 7 d and 3 months. The frequency of Th17 cells increased to a peak at three days, and subsequently decreased with a higher level than baseline. Our data revealed that the variation in Th1, Th17, CXCL16 and homocysteine in peripheral blood of patients with stenting may be implicated in inflammation after intracranial and cervical stent implantation. A better understanding of these factors will provide help for further drug design and clinical therapy. PMID- 27669633 TI - Aging with autism spectrum disorder: an emerging public health problem. AB - From 1943, when Leo Kanner originally described autism, and to the first objective criteria for "infantile autism" in DSM-III and the inclusion of Asperger's disorder in DSM-IV, the subsequent classification scheme for autistic disorders has led to a substantial change with the 2013 issuance of the DSM-5 by including subcategories into one umbrella diagnosis of autism spectrum disorder (ASD) (Baker, 2013). ASD is a lifelong neurodevelopmental disorder, characterized by social and communication impairments and restricted, stereotypical patterns of behavior (Baker, 2013). It is currently expected that most, or all of the actual cases of ASD, are identified in a timely way (i.e. in early childhood). However, there are many undiagnosed older adults who may have met the current diagnostic criteria for ASD as children, but never received such a diagnosis due to the fact it had yet to be established. In addition, some patients with relatively less impairing phenotypes may escape formal diagnosis in childhood, only to later be diagnosed in adulthood. Nevertheless, the first generation of diagnosed patients with ASD is now in old age. Many such ASD patients have needed family and institutional support for their lives subsequent to childhood diagnosis. Due to aging and death of their parents and other supportive figures leading to a loss of social structures, there is no better time than now for the medical community to act. PMID- 27669632 TI - A global assessment of phthalates burden and related links to health effects. AB - Phthalates are ubiquitous environmental contaminants which are used in industry as plasticizers and additives in cosmetics. They are classified as Endocrine Disrupting Chemicals (EDCs) which impair the human endocrine system inducing fertility problems, respiratory diseases, childhood obesity and neuropsychological disorders. The aim of this review is to summarize the current state of knowledge on the toxicity that phthalates pose in humans based on human biomonitoring studies conducted over the last decade. Except for conventional biological matrices (such as urine and serum), amniotic fluid, human milk, semen, saliva, sweat, meconium and human hair are also employed for the estimation of exposure and distribution of pollutants in the human body, although data are not enough yet. Children are highly exposed to phthalates relative to adults and in most studies children's daily intake surpasses the maximum reference dose (RfD) set from US Environmental Protection Agency (US EPA). However, the global trend is that human exposure to phthalates is decreasing annually as a result of the strict regulations applied to phthalates. PMID- 27669634 TI - Effect of HEMA Phosphate as an Alternative to Phosphoric Acid for Dentin Treatment Prior to Hybridization with Etch-and-Rinse Adhesive Systems. AB - PURPOSE: To evaluate the effect of dentin treatment using HEMA phosphate (HEMA-P) on the microtensile bond strength (MUTBS) and nanoleakage of an etch-and-rinse adhesive system. MATERIALS AND METHODS: The occlusal surfaces of human molars were wet ground until superficial dentin was exposed. The specimens were then assigned to two groups according to dentin treatment: PA: 37% H3PO4 for 15 s; or HP: HEMA-P for 15 s. Adper Single Bond 2 was applied to the treated dentin surfaces and resin composite buildups were incrementally constructed over them. After 24-h storage in artificial saliva at 37 degrees C, the bonded teeth were cut into resin-dentin sticks with a cross-sectional area of 1 mm2, which were submitted to MUTBS testing immediately or after 3 months of storage in artificial saliva at 37 degrees C. Nanoleakage was assessed using SEM/EDS, and the interaction between dentin and H3PO4 or HEMA-P was evaluated by combining micro Raman and FT-IR spectroscopy. The data were analyzed using two-way ANOVA and Tukey's HSD post-hoc test (alpha = 0.05). RESULTS: HP presented significantly higher MUTBS than PA at both times (p < 0.05). Both treatments maintained MUTBS stability after 3 months of artificial saliva storage (p > 0.005). At both times, PA presented higher nanoleakage than HP (p < 0.05). CONCLUSIONS: Both dentin treatments maintained MUTBS stability after 3 months of artificial saliva storage. The use of HEMA-P was associated with less nanoleakage than was traditional phosphoric-acid etching. PMID- 27669635 TI - Tribochemical Glass Ceramic Coating as a New Approach for Resin Adhesion to Zirconia. AB - PURPOSE: To investigate the effects of a novel tribochemical silica coating technique with powders made from feldspathic ceramic and leucite-based ceramic on the bond strength of zirconia to resin cement before and after aging. MATERIALS AND METHODS: Zirconia blocks were divided into 3 groups according to the material used for airborne-particle abrasion: 1) SP (control): silica-coated alumina particles; 2) FP: feldspathic ceramic powder; 3) LP: leucite glass-ceramic powder. After silanization, composite resin cylinders were cemented on the zirconia surface using a dual-curing resin cement. Prior to the shear bond strength (SBS) test, half of the samples (n = 15) were stored in distilled water for 24 h; the other half (n = 15) were submitted to aging (10,000 thermocycles of 5 degrees C to 55 degrees C; 150 days of water storage). The bond strength data were analyzed using two-way ANOVA and Tukey's test (alpha = 0.05). Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and x-ray diffraction analysis were performed. RESULTS: The initial bond strengths did not differ significantly between the groups (p = 0.053). However, after aging procedures, airborne-particle abrasion with feldspathic ceramic powder (FP) resulted in higher values of bond strength (p = 0.0001). SEM and EDS indicated that all the treatments promoted silica deposition on the Y-TZP surface ceramic. Airborne-particle abrasion with FP and LP induced a lower percentage of the monoclinic phase. CONCLUSION: Airborne abrasion with fine feldspathic ceramic particles is a novel tribochemical technique and appears to be suitable for improving the bond strength between zirconia and resin cements. PMID- 27669636 TI - Comparison of Different Protocols for Performing Adhesive Restorations in Primary Teeth - A Retrospective Clinical Study. AB - PURPOSE: To examine the influence of different adhesive restoration protocols on the survival of composite resin restorations in primary teeth. MATERIALS AND METHODS: This study included 601 patients at risk of caries (319 males and 282 females), with a mean age of 6.6 years (range: 1 to 13 years) and an average need for 3.6 restorations per patient (range: 1 to 20). The mean observation period was 1.3 years (+/- 1.4), with a maximum of 7 years. Six different adhesive restoration protocols with respect to etching, adhesives, and composite materials were analyzed. The statistical analyses included descriptive analyses and a Cox regression model from which hazard ratios (HR with 95% CI) for protocols and possible predictors were calculated. RESULTS: The mean dmft was 6.6 (+/- 4.0), which indicates a high risk population. Secondary caries was the most frequent reason for loss of restoration in this study (52.2%). Out of 2146 restorations, 368 failed; the mean annual failure rate was 13.2%. Adhesive restoration protocols that employed a self-etching system performed significantly better (HR range: 1.0 to 1.8) than did the etch-and-rinse system (HR range: 1.8 to 2.8). Protocols using only flowable materials had a moderately increased probability of failure. CONCLUSION: With respect to the practice-based study design, young age, and high risk of caries in this population, comparatively high failure rates were observed for direct composite restorations in primary dentition, but adhesive restoration protocols using self-etching adhesives in combination with universal composites yielded a higher probability of survival. PMID- 27669637 TI - Large increase in the prevalence of self-reported diabetes based on a nationally representative survey in Hungary. AB - AIMS: To estimate and compare the prevalence of self-reported diabetes based on nationally representative surveys of the Hungarian adult population in 2002 (published data - Hungarostudy) and a survey in 2012. METHODS: A cross-sectional computer-assisted telephone interview survey on a stratified representative sample of community-dwelling adults (n=1000) in 2012. To describe self-reported diabetes prevalence and its temporal changes generalized linear models were used and results were compared to figures from Hungarostudy. RESULTS: Age standardized prevalence of self-reported type 2 diabetes was 11.7% (95%CI 10.0-13.8%) without gender or rural-urban differences in 2012. People with self-reported diabetes were older than controls (mean [SE]: 63.9 [0.9] vs. 45.9 [0.3] years, p<0.0001). The prevalence of diabetes sharply increased after 40 years of age and peaked at age 70 (27.7% [2.5], page*age<0.0001). The prevalence of self-reported diabetes increased by 89% (OR 1.89, 95%CI 1.53-2.32) from 6.2 to 11.7% between the two surveys with the most pronounced increase in the age group 55-64 years (from 11.6 to 24.4%). CONCLUSIONS: We reported an alarming increase in the prevalence of self-reported type 2 diabetes in the last decade that mostly affects working age people. If this trend continues, a major public health crisis in Hungary can be envisaged. PMID- 27669638 TI - Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. AB - BACKGROUND & AIMS: This trial was performed to evaluate the effects of probiotic intake on disability, mental health and metabolic condition in subjects with multiple sclerosis (MS). METHODS: This randomized double-blind placebo-controlled clinical trial was conducted among 60 MS patients. Participants were randomly allocated into two groups to receive either a probiotic capsule (n = 30) or placebo containing starch (n = 30) for 12 weeks. Expanded disability status scale (EDSS) scoring and parameters of mental health were recorded at the baseline and 12 weeks after the intervention. RESULTS: Compared with the placebo, probiotic intake improved EDSS (-0.3 +/- 0.6 vs. +0.1 +/- 0.3, P = 0.001), beck depression inventory (-5.6 +/- 4.9 vs. -1.1 +/- 3.4, P < 0.001), general health questionnaire (-9.1 +/- 6.2 vs. -2.6 +/- 6.4, P < 0.001) and depression anxiety and stress scale (-16.5 +/- 12.9 vs. -6.2 +/- 11.0, P = 0.001). In addition, changes in high-sensitivity C-reactive protein (-1.3 +/- 3.5 vs. +0.4 +/- 1.4 MUg/mL, P = 0.01), plasma nitric oxide metabolites (+1.0 +/- 7.9 vs. -6.0 +/- 8.3 MUmol/L, P = 0.002) and malondialdehyde (MDA) (+0.009 +/- 0.4 vs. +0.3 +/- 0.5 MUmol/L, P = 0.04) in the probiotic group were significantly different from the changes in these parameters in the placebo group. Additionally, the consumption of probiotic capsule significantly decreased serum insulin (-2.9 +/- 3.7 vs. +1.1 +/- 4.8 MUIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (-0.6 +/- 0.8 vs.+0.2 +/- 1.0, P = 0.001), Beta cell function (-12.1 +/- 15.5 vs. +4.4 +/- 17.5, P < 0.001) and total-/HDL-cholesterol (-0.1 +/- 0.3 vs.0.1 +/- 0.3, P = 0.02), and significantly increased quantitative insulin sensitivity check index (+0.01 +/- 0.02 vs. -0.005 +/- 0.01, P < 0.001) and HDL cholesterol levels (2.7 +/- 3.4 vs. 0.9 +/- 2.9 mg/dL, P = 0.02) compared with the placebo. CONCLUSIONS: Our study demonstrated that the use of probiotic capsule for 12 weeks among subjects with MS had favorable effects on EDSS, parameters of mental health, inflammatory factors, markers of insulin resistance, HDL-, total-/HDL-cholesterol and MDA levels. PMID- 27669639 TI - Activation of NPFF2 receptor stimulates neurite outgrowth in Neuro 2A cells through activation of ERK signaling pathway. AB - Neurite outgrowth is an important process in neural regeneration and plasticity, especially after neural injury, and recent evidence indicates that several Galphai/o protein-coupled receptors play an important role in neurite outgrowth. The neuropeptide (NP)FF system contains two Galphai/o protein-coupled receptors, NPFF1 and NPFF2 receptors, which are mainly distributed in the central nervous system. The aim of the present study was to determine whether the NPFF system is involved in neurite outgrowth in Neuro 2A cells. We showed that Neuro 2A cells endogenously expressed NPFF2 receptor, and the NPFF2 receptor agonist dNPA inhibited cyclic adenosine monophosphate (cAMP) production stimulated by forskolin in Neuro 2A cells. We also demonstrated that NPFF and dNPA dose dependently induced neurite outgrowth in Neuro 2A cells, which was completely abolished by the NPFF receptor antagonist RF9. Pretreatment with mitogen activated protein kinase inhibitors PD98059 and U0126 decreased dNPA-induced neurite outgrowth. In addition, dNPA increased phosphorylation of extracellular signal-regulated kinase (ERK) in Neuro 2A cells, which was completely antagonized by pretreatment with U0126. Our results suggest that activation of NPFF2 receptor stimulates neurite outgrowth in Neuro 2A cells through activation of the ERK signaling pathway. Moreover, NPFF2 receptor may be a potential therapeutic target for neural injury and degeneration in the future. PMID- 27669640 TI - Perioperative atherothrombotic stroke: Not everything is what it seems. PMID- 27669641 TI - Downregulation of Nrf2 promotes autophagy-dependent osteoblastic differentiation of adipose-derived mesenchymal stem cells. AB - Adipose derived stem cells (ADSCs) are an important source of stem cells for tissue repair and regeneration; therefore, understanding the mechanisms that regulate stem cell differentiation into a specific lineage is critical. The NF-E2 related factor 2 (Nrf2) pathway and autophagy promote cell survival in response to oxidative stress. However, the roles of Nrf2 and autophagy in bone metabolism under oxidative stress are controversial. Here, we explored the involvement of Nrf2 signaling and autophagy on the differentiation of ADSCs under conditions of oxidative stress. Exposure of ADSCs to H2O2 promoted reactive oxygen species (ROS) accumulation concomitant with the reduction of cell viability, upregulation of Nrf2, the induction of apoptosis and autophagy, and the promotion of osteogenesis. Suppression of autophagic activity at particular stages resulted in the activation of the Nrf2 pathway, whereas osteoblastic differentiation of ADSCs was inhibited upon ROS stimulation. Silencing of Nrf2 promoted autophagy and osteoblastic differentiation upon ROS stimulation in vitro, and this effect was confirmed in vivo in a mouse model, in which bone formation was enhanced in mice receiving Nrf2-knockdown ADSCs. Taken together, these findings indicate that a negative interaction between the Nrf2 pathway and autophagy may modulate oxidative stress-induced ADSC osteogenesis, and suggest that Nrf2 is a potential target to regulate the differentiation of ADSCs into a specific lineage. PMID- 27669642 TI - Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology. AB - Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. PMID- 27669643 TI - The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines. AB - Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. PMID- 27669644 TI - The characterization and validation of 17beta-estradiol binding aptamers. AB - The rapid and sensitive detection of small molecules is garnering increasing importance, and aptamers show great promise in replacing expensive, elaborate detection platforms exploiting chromatographic separation or antibody-based assays. The characterization of aptamer interaction with small molecule targets is not facile, and there is a mature need for a rapid, high-throughput technique for the analysis of aptamer-small molecule kinetics and affinity. In this work we present methodologies for the evaluation of aptamer-small molecule interactions, using the aptamers reported against the steroid 17beta-estradiol as a model system. Microscale thermophoresis, apta-PCR affinity assay and surface plasmon resonance were explored to evaluate the reported aptamers' binding properties in terms of affinity and specificity, and were demonstrated to be successfully applied to the analysis of aptamer-small molecule interactions. PMID- 27669645 TI - Impact of Shaggy Aorta in Patients with Abdominal Aortic Aneurysm Following Open or Endovascular Aneurysm Repair. AB - OBJECTIVE: To analyze the impact of the presence of shaggy aorta on 30 day morbidity and mortality and long-term survival in patients undergoing abdominal aortic aneurysm (AAA) repair. METHODS: This retrospective observational study included 447 consecutive patients who underwent AAA repair between January 2009 and December 2012. The study included 209 patients (47%) having open surgical repair (OSR) and 238 patients (53%) having endovascular aneurysm repair (EVAR). RESULTS: Of the 447 patients having elective AAA repair, 48 patients (11%) had shaggy aorta. Both the OSR (p = .005) and EVAR group (p = .007) demonstrated a higher 30 day morbidity and mortality in patients with shaggy aorta. On multivariate regression analysis, patients with shaggy aorta had 4.1 fold (95% CI = 1.7-9.7; p = .002) increase in 30 day morbidity and mortality. According to the Kaplan-Meier analysis, patients with shaggy aorta had significantly decreased long-term overall survival in comparison with the non-shaggy group (log-rank test; p = .005), and this resulted from comorbidities. CONCLUSIONS: Shaggy aorta is a prominent risk factor associated with 30 day morbidity and mortality. Poor long-term survival was expected in patients with shaggy aorta. PMID- 27669646 TI - Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. AB - Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1.07 to 1.82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1.54 (95% CI 1.09-2.18). Our optimal information size analysis showed that any randomised controlled trial aiming to detect a true difference in cardiovascular risk between treatment groups receiving exogenous testosterone and their controls (with a two-sided p value of 0.05 and a power of 80%) would require at least 17 664 participants in each trial group. Therefore, given the challenge of adequately powering clinical trials for rare outcomes, rigorous observational studies are needed to clarify the association between testosterone-replacement therapy and major adverse cardiovascular outcomes. PMID- 27669648 TI - Anammox Biochemistry: a Tale of Heme c Proteins. AB - Anaerobic ammonium-oxidizing (anammox) bacteria are one of the latest scientific discoveries in the biogeochemical nitrogen cycle. These microorganisms are able to oxidize ammonium (NH4+) with nitrite (NO2-) as the oxidant instead of oxygen and form dinitrogen (N2) as the end product. Recent research has shed a light on the biochemistry underlying anammox metabolism with two key intermediates, nitric oxide (NO) and hydrazine (N2H4). Substrates and intermediates are converted exploiting the catalytic and electron-transfer potentials of c-type heme proteins known from numerous biochemical reactions and that have acquired new functionality in anammox biochemistry. On a global scale, anammox bacteria significantly contribute to the removal of fixed nitrogen from the environment and the process finds rapidly increasing interest in wastewater treatment. PMID- 27669647 TI - The Tail That Wags the Dog: How the Disordered C-Terminal Domain Controls the Transcriptional Activities of the p53 Tumor-Suppressor Protein. AB - The p53 tumor suppressor is a transcription factor (TF) that exerts antitumor functions through its ability to regulate the expression of multiple genes. Within the p53 protein resides a relatively short unstructured C-terminal domain (CTD) that remarkably participates in virtually every aspect of p53 performance as a TF. Because these aspects are often interdependent and it is not always possible to dissect them experimentally, there has been a great deal of controversy about the CTD. In this review we evaluate the significance and key features of this interesting region of p53 and its impact on the many aspects of p53 function in light of previous and more recent findings. PMID- 27669649 TI - Cellular Functions and Molecular Mechanisms of the ESCRT Membrane-Scission Machinery. AB - The endosomal sorting complex required for transport (ESCRT) machinery is an assembly of protein subcomplexes (ESCRT I-III) that cooperate with the ATPase VPS4 to mediate scission of membrane necks from the inside. The ESCRT machinery has evolved as a multipurpose toolbox for mediating receptor sorting, membrane remodeling, and membrane scission, with ESCRT-III as the major membrane remodeling component. Cellular membrane scission processes mediated by ESCRT-III include biogenesis of multivesicular endosomes, budding of enveloped viruses, cytokinetic abscission, neuron pruning, plasma membrane wound repair, nuclear pore quality control, nuclear envelope reformation, and nuclear envelope repair. We describe here the involvement of the ESCRT machinery in these processes and review current models for how ESCRT-III-containing multimeric filaments serve to mediate membrane remodeling and scission. PMID- 27669652 TI - High Resolution non-Markovianity in NMR. AB - Memoryless time evolutions are ubiquitous in nature but often correspond to a resolution-induced approximation, i.e. there are correlations in time whose effects are undetectable. Recent advances in the dynamical control of small quantum systems provide the ideal scenario to probe some of these effects. Here we experimentally demonstrate the precise induction of memory effects on the evolution of a quantum coin (qubit) by correlations engineered in its environment. In particular, we design a collisional model in Nuclear Magnetic Resonance (NMR) and precisely control the strength of the effects by changing the degree of correlation in the environment and its time of interaction with the qubit. We also show how these effects can be hidden by the limited resolution of the measurements performed on the qubit. The experiment reinforces NMR as a test bed for the study of open quantum systems and the simulation of their classical counterparts. PMID- 27669650 TI - Mechanism and Regulation of NLRP3 Inflammasome Activation. AB - Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed 'inflammasomes'. The biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL 1beta) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanism and regulation of its activation remain unclear. In this review we summarize current understanding of the mechanism and regulation of NLRP3 inflammasome activation as well as recent advances in the noncanonical and alternative inflammasome pathways. PMID- 27669651 TI - Macromolecular Crowding In Vitro, In Vivo, and In Between. AB - Biochemical processes take place in heterogeneous and highly volume-occupied or crowded environments that can considerably influence the reactivity and distribution of participating macromolecules. We summarize here the thermodynamic consequences of excluded-volume and long-range nonspecific intermolecular interactions for macromolecular reactions in volume-occupied media. In addition, we summarize and compare the information content of studies of crowding in vitro and in vivo. We emphasize the importance of characterizing the behavior not only of labeled tracer macromolecules but also the composition and behavior of unlabeled macromolecules in the immediate vicinity of the tracer. Finally, we propose strategies for extending quantitative analyses of crowding in simple model systems to increasingly complex media up to and including intact cells. PMID- 27669653 TI - National Surgical Trends and Perioperative Outcomes of Midurethral Sling Placement for Stress Urinary Incontinence. AB - OBJECTIVE: To determine contemporary trends, patient characteristics, and outcomes for midurethral sling placement (MUS) at inpatient and ambulatory facilities from a national database. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified 7767 women who underwent isolated MUS 2006-2012. We stratified patients by hospitalization type (outpatient vs hospitalization). Primary outcomes were 30-day complications, readmissions, and reoperations. Multivariable logistic regression was used to determine patient and surgery factors associated with adverse perioperative outcomes. RESULTS: Among the 7767 women undergoing MUS, 84.3% underwent outpatient surgery (n = 6547), with greater use of outpatient facilities over time (P < .001). Overall, 3.9% of patients (n = 300) experienced one or more postoperative complications. Complications were more likely among inpatients (7.4% vs 3.2%; odds ratio [OR] 0.48, confidence interval [CI] 0.36-0.64, P < .001), with gynecologists as compared to urologists (4.4% vs 3.1%; OR 1.53, CI 1.16-2.02, P = .003), and with resident participation (5.1% vs 3.7%; OR 1.32, CI 1.01-1.73, P = .04). On multivariable analysis, outpatients were less likely to experience readmissions (0.9% vs 2.8%; OR 0.2, CI 0.09-0.56, P = .002) or undergo reoperation (0.3% vs 3.1%; OR 0.10, CI 0.02-0.38, P = .001). CONCLUSION: Use of outpatient surgical centers for MUS is increasing, with lower rates of complications, readmissions, and reoperations compared to inpatient treatment. Although there is a difference in complications by specialty and with resident involvement, overall incidence of complications is low. PMID- 27669654 TI - Impact of Anticoagulant and Antiplatelet Drugs on Perioperative Outcomes of Robotic-assisted Partial Nephrectomy. AB - OBJECTIVE: To evaluate the impact of anticoagulant (AC) or antiplatelet (AP) therapy on the morbidity of robot-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: From 2011 to 2015, we retrospectively analyzed a prospectively maintained institutional review board-approved database of RAPN from 2 academic departments of urology. We evaluated the occurrence of overall complications and hemorrhagic complications (pseudoaneurysm, arteriovenous fistula, hematoma, transfusion). Patients with therapeutic AC or AP, stopped or not before surgery, were compared with patients without therapeutic AC or AP. A logistic regression model was used to identify predictors of complications. RESULTS: Out of 533 patients who underwent RAPN, 70 had AC or AP (50% aspirin, 25% clopidogrel, 28% AC, 8% direct oral AC). Clopidogrel, AC, and direct oral AC were always stopped preoperatively. Aspirin was continued in 25% of the cases. In univariate analysis, overall complications (39.2% vs 17.4%; P = .001) and hemorrhagic complications (32.7% vs 9.6%; P <.001) were higher in patients on AC or AP. Hospital stay was longer in the group with therapeutic AC or AP treatment (5.1 vs 3.9 days; P <.001). In multivariate analysis, predictors of complications were intake of therapeutic AC (odds ratio [OR] = 4.3, IC95% [1.2-15.9], P = .03) and tumor size (OR = 1.8, IC95% [1.3-7.2], P = .03). Patients on aspirin tended to have more complications (OR = 2.4; IC95% [0.4-9.3]; P = .15). CONCLUSION: AP and therapeutic AC increase the morbidity of RAPN. These treatments should be taken into account in treatment decision-making algorithm of small renal masses. PMID- 27669657 TI - Tyrosine kinase receptor c-ros-oncogene 1 mediates TWIST-1 regulation of human mesenchymal stem cell lineage commitment. AB - The TWIST-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor important in mediating skeletal and head mesodermal tissue development. Bone marrow-derived mesenchymal stem/stromal cells (BMSC), express high levels of TWIST-1, which is down regulated during ex vivo expansion. Cultured BMSC over expressing TWIST-1 display decreased capacity for osteogenic differentiation and an enhanced capacity to undergo adipogenesis, suggesting that TWIST-1 is a mediator of lineage commitment. However, little is known regarding the mechanism(s) by which TWIST-1 mediates cell fate determination. In this study, microarray analysis was used to identify a novel downstream TWIST-1 target, tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1), which was down regulated in TWIST-1 over-expressing BMSC. Chromatin immunoprecipitation analysis showed that TWIST-1 directly bound to two E-box binding sites on the proximal C-ROS-1 promoter. Knock-down of C-ROS-1 in human BMSC and cranial bone cells resulted in a decreased capacity for osteogenic differentiation in vitro. Conversely, suppression of C-ROS-1 in BMSC resulted in an enhanced capacity to undergo adipogenesis. Furthermore, reduced C-ROS-1 levels led to activation of different components of the PI3K/AKT/mTORC1 signalling pathway during osteogenic and adipogenic differentiation. Collectively, these data suggest that C-ROS-1 is involved in BMSC fate switching between osteogenesis and adipogenesis, mediated via PI3K/AKT/mTORC1 signalling. PMID- 27669655 TI - Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model. AB - Tumor-selective oncolytic vesicular stomatitis viruses (VSVs) are being evaluated in clinical trials. Here, we report that the MPC-11 murine plasmacytoma model is so extraordinarily susceptible to oncolytic VSVs that a low dose of virus leads to extensive intratumoral viral replication, sustained viremia, intravascular coagulation, and a rapidly fatal tumor lysis syndrome (TLS). Rapid softening, shrinkage and hemorrhagic necrosis of flank tumors was noted within 1-2 days after virus administration, leading to hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, increase in plasma cell free DNA, lymphopenia, consumptive coagulopathy, increase in fibrinogen degradation products, decreased liver function tests, dehydration, weight loss, and euthanasia or death after 5-8 days. Secondary viremia was observed but viral replication in normal host tissues was not detected. Toxicity could be mitigated by using VSVs with slowed replication kinetics, and was less marked in animals with smaller flank tumors. The MPC-11 tumor represents an interesting model to further study the complex interplay of robust intratumoral viral replication, tumor lysis, and associated toxicities in cases where tumors are highly responsive to oncolytic virotherapy. PMID- 27669656 TI - Inhibition of BET proteins and epigenetic signaling as a potential treatment for osteoporosis. AB - Histone modifications are important for maintaining the transcription program. BET proteins, an important class of "histone reading proteins", have recently been described as essential in bone biology. This study presents the therapeutic opportunity of BET protein inhibition in osteoporosis. We find that the pharmacological BET protein inhibitor JQ1 rescues pathologic bone loss in a post ovariectomy osteoporosis model by increasing the trabecular bone volume and restoring mechanical properties. The BET protein inhibition suppresses osteoclast differentiation and activity as well as the osteoblastogenesis in vitro. Moreover, we show that treated non-resorbing osteoclasts could still activate osteoblast differentiation. In addition, specific inhibition of BRD4 using RNA interference inhibits osteoclast differentiation but strongly activates osteoblast mineralization activity. Mechanistically, JQ1 inhibits expression of the master osteoclast transcription factor NFATc1 and the transcription factor of osteoblast Runx2. These findings strongly support that targeting epigenetic chromatin regulators such as BET proteins may offer a promising alternative for the treatment of bone-related disorders such as osteoporosis. PMID- 27669659 TI - In-vivo, non-invasive detection of hyperglycemic states in animal models using mm wave spectroscopy. AB - Chronic or sustained hyperglycemia associated to diabetes mellitus leads to many medical complications, thus, it is necessary to track the evolution of patients for providing the adequate management of the disease that is required for the restoration of the carbohydrate metabolism to a normal state. In this paper, a novel monitoring approach based on mm-wave spectroscopy is comprehensively described and experimentally validated using living animal models as target. The measurement method has proved the possibility of non-invasive, in-vivo, detection of hyperglycemia-associated conditions in different mouse models, making possible to clearly differentiate between several hyperglycemic states. PMID- 27669660 TI - Observation of a new superfluid phase for 3He embedded in nematically ordered aerogel. AB - In bulk superfluid 3He at zero magnetic field, two phases emerge with the B-phase stable everywhere except at high pressures and temperatures, where the A-phase is favoured. Aerogels with nanostructure smaller than the superfluid coherence length are the only means to introduce disorder into the superfluid. Here we use a torsion pendulum to study 3He confined in an extremely anisotropic, nematically ordered aerogel consisting of ~10 nm-thick alumina strands, spaced by ~100 nm, and aligned parallel to the pendulum axis. Kinks in the development of the superfluid fraction (at various pressures) as the temperature is varied correspond to phase transitions. Two such transitions are seen in the superfluid state, and we identify the superfluid phase closest to Tc at low pressure as the polar state, a phase that is not seen in bulk 3He. PMID- 27669658 TI - Reduced femoral bone mass in both diet-induced and genetic hyperlipidemia mice. AB - Growing evidence argues for a relationship between lipid and bone metabolisms with inconsistent conclusions. Sphingosine-1-phosphate (S1P) has been recognized as a suitable candidate for possible link between lipid metabolism and bone metabolism. This study was designed to investigate the effects of hyperlipidemia on bone metabolism using diet-induced and genetic-induced hyperlipidemia animal models and to explore whether S1P is involved. Wild-type mice and low-density lipoprotein receptor gene deficient (LDLR-/-) mice at age of 8weeks were placed on either control diet or high-fat diet (HFD) for 12weeks. Bone structural parameters were determined using microCT. Cross-linked type I collagen (CTx) and S1P levels in plasma were measured by ELISA methods. Bone marrow cells from wild type and LDLR-/- mice were induced to differentiate into osteoblasts, osteoclasts and adipocytes respectively. Gene expressions in distal femur metaphyses and cultured cells were studied by qRT-PCR. Moderate hypercholesterolemia was found in HFD-feeding mice; severe hypercholesterolemia and moderate hypertriglyceridemia were present in LDLR-/- mice. Femoral trabecular bone mass was reduced in both diet-induced and genetic hyperlipidemia mice. Mice feeding on HFD showed higher CTx levels, and mice with hyperlipidemia had elevated S1P levels. Correlation analysis found a positive correlation between CTx and S1P levels. Lower Runx2 expression and higher TRAP expression were found in both diet induced and genetic hyperlipidemia mice, indicating decreased osteoblastic functions and increased osteoclastic functions in these mice. Bone marrow cells from LDLR-/- mice also showed increased adipogenesis and inhibited osteogenesis accompanied by enhanced PPARgamma expression. In conclusion, our study found decreased bone mass in both diet-induced and genetic hyperlipidemia mice. PMID- 27669661 TI - Medical interventions for the prevention of platinum-induced hearing loss in children with cancer. AB - BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. One of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the efficacy of medical interventions to prevent hearing loss and to determine possible effects of these interventions on anti-tumour efficacy, toxicities other than hearing loss and quality of life in children with cancer treated with platinum-based therapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6), MEDLINE (PubMed) (1945 to 8 July 2016) and EMBASE (Ovid) (1980 to 8 July 2016). In addition, we handsearched reference lists of relevant articles and we assessed the conference proceedings of the International Society for Paediatric Oncology (2006 up to and including 2015), the American Society of Pediatric Hematology/Oncology (2007 up to and including 2016) and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (2010 up to and including 2015). We scanned the International Standard Randomized Controlled Trial Number (ISRCTN) Register (www.isrctn.com) and the National Institute of Health Register (www.clinicaltrials.gov) for ongoing trials (both searched on 12 July 2016). SELECTION CRITERIA: Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) evaluating platinum-based therapy together with an otoprotective medical intervention versus platinum-based therapy with placebo, no additional treatment or another protective medical intervention in children with cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, data extraction, risk of bias assessment and GRADE assessment of included studies, including adverse effects. We performed analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We identified two RCTs and one CCT (total number of participants 149) evaluating the use of amifostine versus no additional treatment in the original version of the review; the updates identified no additional studies. Two studies included children with osteosarcoma, and the other study included children with hepatoblastoma. Children received cisplatin only or a combination of cisplatin and carboplatin, either intra-arterially or intravenously. Pooling of results of the included studies was not possible. However, in the individual studies there was no significant difference in symptomatic ototoxicity only (that is, grade 2 or higher) and combined asymptomatic and symptomatic ototoxicity (that is, grade 1 or higher) between children treated with or without amifostine. Only one study, including children with osteosarcoma treated with intra-arterial cisplatin, provided information on tumour response, defined as the number of participants with a good or partial remission. The available data analysis (data were missing for one participant), best case scenario analysis and worst case scenario analysis all showed a difference in favour of amifostine, but this difference was significant only in the worst case scenario analysis (P = 0.04). There was no information on survival for any of the included studies. Only one study, including children with osteosarcoma treated with intra-arterial cisplatin, provided data on the number of participants with adverse effects other than ototoxicity grade 3 or higher. There was a significant difference in favour of the control group in the occurrence of vomiting grade 3 or 4 (risk ratio (RR) 9.04; 95% confidence interval (CI) 1.99 to 41.12; P = 0.004). There was no significant difference between treatment groups for cardiotoxicity and renal toxicity grade 3 or 4. None of the studies evaluated quality of life. The quality of evidence for the different outcomes was low. We found no eligible studies for possible otoprotective medical interventions other than amifostine and other types of malignancies. AUTHORS' CONCLUSIONS: At the moment there is no evidence from individual studies in children with osteosarcoma or hepatoblastoma treated with different platinum analogues and dosage schedules that underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment. Since pooling of results was not possible and all studies had serious methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. Based on the currently available evidence, we are unable to give recommendations for clinical practice. We identified no eligible studies for other possible otoprotective medical interventions and other types of malignancies, so no conclusions can be made about their efficacy in preventing ototoxicity in children treated with platinum-based therapy. More high quality research is needed. PMID- 27669662 TI - Advent of Continents: A New Hypothesis. AB - The straightforward but unexpected relationship presented here relates crustal thickness to magma type in the Izu-Ogasawara (Bonin) and Aleutian oceanic arcs. Volcanoes along the southern segment of the Izu-Ogasawara arc and the western Aleutian arc (west of Adak) are underlain by thin crust (10-20 km). In contrast those along the northern segment of the Izu-Ogasawara arc and eastern Aleutian arc are underlain by crust ~35 km thick. Interestingly, andesite magmas dominate eruptive products from the former volcanoes and mostly basaltic lavas erupt from the latter. According to the hypothesis presented here, rising mantle diapirs stall near the base of the oceanic crust at depths controlled by the thickness of the overlying crust. Where the crust is thin, melting occurs at relatively low pressures in the mantle wedge producing andesitic magmas. Where the crust is thick, melting pressures are higher and only basaltic magmas tend to be produced. The implications of this hypothesis are: (1) the rate of continental crust accumulation, which is andesitic in composition, would have been greatest soon after subduction initiated on Earth, when most crust was thin; and (2) most andesite magmas erupted on continental crust could be recycled from "primary" andesite originally produced in oceanic arcs. PMID- 27669663 TI - Chlorpyrifos exposure affects fgf8, sox9, and bmp4 expression required for cranial neural crest morphogenesis and chondrogenesis in Xenopus laevis embryos. AB - Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos. This study investigated the effects of exposure to different CPF concentrations (10, 15 and 20 mg/L) on Xenopus laevis embryos from stage 4/8 to stage 46. Some of the morphological changes we detected in CPF-exposed embryos included cranial neural crest cell (NCC)-derived structures. For this reason, we analyzed the expression of select genes involved in hindbrain patterning (egr2), cranial neural crest chondrogenesis, and craniofacial development (fgf8, bmp4, sox9, hoxa2 and hoxb2). We found that CPF exposure induced a reduction in transcription of all the genes involved in NCC-dependent chondrogenesis, with largest reductions in fgf8 and sox9; whereas, in hindbrain, we did not find any alterations in egr2 expression. Changes in the expression of fgf8, bmp4, and sox9, which are master regulators of several developmental pathways, have important implications. If these changes are confirmed to belong to a general pattern of alterations in vertebrates prenatally exposed to OP, they might be useful to assess damage during vertebrate embryo development. Environ. Mol. Mutagen. 57:589-604, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27669664 TI - Oral Human Abuse Potential of Oxycodone DETERx(r) (Xtampza(r) ER). AB - Oxycodone DETERx(r) (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended-release, microsphere-in-capsule, abuse-deterrent formulation designed to retain its extended-release properties after tampering (eg, chewing/crushing). This randomized, double-blind, placebo-controlled, triple-dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate-release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high-fat, high-calorie meal and fasted), chewed oxycodone DETERx (high-fat, high-calorie meal and fasted), crushed immediate release oxycodone (fasted), and placebo (high-fat, high-calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty-eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate-release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax ) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate-release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate-release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate-release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate the lower oral abuse potential of chewed and intact oxycodone DETERx than crushed immediate-release oxycodone. PMID- 27669665 TI - Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients. AB - Specific changes in immune repertoires at genetic level responding to the lethal H7N9 virus are still poorly understood. We performed deep sequencing on the T and B cells from patients recently infected with H7N9 to explore the correlation between clinical outcomes and immune repertoire alterations. T and B cell repertoires display highly dynamic yet distinct clonotype alterations. During infection, T cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy chain repertoire recovers. Patient recovery is correlated to the diversity of T cell and B cell repertoires in different ways - higher B cell diversity and lower T cell diversity are found in survivors. The sequences clonally related to known antibodies with binding affinity to H7 hemagglutinin could be identified from survivors. These findings suggest that utilizing deep sequencing may improve prognostication during influenza infection and could help in development of antibody discovery methodologies for the treatment of virus infection. PMID- 27669666 TI - Liver X Receptors and their Agonists: Targeting for Cholesterol Homeostasis and Cardiovascular Diseases. AB - Liver X receptors alpha (LXRalpha) and beta (LXRbeta) are essential for protection against cardiovascular diseases. LXRs are members of the nuclear receptor superfamily of DNA-binding transcription factors and act as sensors of cholesterol homeostasis. In this review, we introduce LXRs and briefly describe the roles of LXRs in reverse cholesterol transport and trans-intestinal cholesterol efflux. We discuss LXR agonists and the downstream genes of LXRs that are involved in the regulation of cholesterol transport. In addition, we describe the cardioprotective effects of LXRs against atherosclerosis, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, and myocardial hypertrophy. Finally, we expand our discussion to the actions of LXRs in atherosclerosis and suggest several potential research avenues that may be of interest to clinicians and basic scientists. The information included herein may be useful for the design of future experimental research studies and may advance the investigation of LXRs as therapeutic targets. PMID- 27669667 TI - Cost-effectiveness of negative pressure wound therapy in patients with many comorbidities and severe wounds of various etiology. AB - This study analyzed a cross-section of patients with severe chronic wounds and multiple comorbidities at an outpatient wound clinic, with regard to the cost effectiveness and cost-benefit of negative pressure wound therapy (intervention) vs. no negative pressure wound therapy (control) at 1 and 2 years. Medicare reimbursement charges for wound care were used to calculate costs. Amputation charges were assessed using diagnosis-related groups. Cost-benefit analysis was based on ulcer-free months and cost-effectiveness on quality-adjusted life-years. Undiscounted costs, benefits, quality-adjusted life-years, undiscounted and discounted incremental net health benefits, and incremental cost-effectiveness ratios were calculated for unmatched and matched cohorts. There were 150 subjects in the intervention group and 154 controls before matching and 103 subjects in each of the matched cohorts. Time to heal for the intervention cohort was significantly shorter compared to the controls (270 vs. 635 days, p = 1.0 * 10-7 , matched cohorts). The intervention cohort had higher benefits and quality adjusted life-year gains compared to the control cohort at years 1 and 2; by year 2, the gains were 68-73% higher. In the unmatched cohorts, the incremental net health benefit was $9,933 per ulcer-free month at year 2 for the intervention; the incremental cost-effectiveness ratio was -825,271 per quality-adjusted life year gained (undiscounted costs and benefits). For the matched cohorts, the incremental net health benefits was only $1,371 per ulcer-free month for the intervention, but the incremental cost-effectiveness ratio was $366,683 per quality-adjusted life-year gained for year 2 (discounted costs and benefits). In a patient population with severe chronic wounds and serious comorbidities, negative pressure wound therapy resulted in faster healing wounds and was more cost-effective with greater cost-benefits than not using negative pressure wound therapy. Regarding overall cost-effectiveness, the intervention was still expensive, but that is the reality amidst limited treatment options for such serious cases of chronic wounds. PMID- 27669668 TI - Is the experience of pain in patients with temporomandibular disorder associated with the presence of comorbidity? AB - The aim of this study was to explore the association between the presence of comorbidities and the pain experience in individual patients with temporomandibular disorder (TMD). This clinical trial comprised 112 patients with TMD pain. For all participants the presence of the following comorbid factors was assessed: pain in the neck; somatization; impaired sleep; and depression. Pain experience was evaluated using the McGill Pain Questionnaire (MPQ). For each subject the TMD-pain experience was assessed for three dimensions - sensory, affective, and evaluative - as specified in the MPQ. The association between comorbid factors and these three dimensions of TMD-pain experience was then evaluated using linear regression models. Univariable regression analyses showed that all comorbid factors, except for one factor, were positively associated with the level of pain, as rated by the sensory description of pain, the affective component of pain, and the evaluative experience of pain. The multivariable regression analyses showed that for all MPQ dimensions, depression showed the strongest associations with pain experience. It was found that in the presence of comorbid disorders, patients with TMD experience elevated levels of TMD pain. This information should be taken into consideration in the diagnostic process, as well as in the choice of treatment. PMID- 27669669 TI - Bilateral C1 laminar hooks combined with C2 pedicle screw fixation in the treatment of atlantoaxial subluxation after Grisel syndrome. AB - BACKGROUND CONTEXT: Many etiologies can lead to atlantoaxial subluxaion. In Grisel syndrome (GS), this subluxation occurs spontaneously after inflammatory processes of the head and neck. Diagnosis is typically based on clinical history and a strong suspicion of this syndrome. Nonsurgical treatment most often resolves the symptoms; however, in some cases surgical treatment is necessary to repair the subluxation. Various surgical techniques and instrumentation systems have been used to treat atlantoaxial subluxation, although there is no consensus regarding the best treatment method for the pediatric population. PURPOSE: To describe a case of atlantoaxial subluxation in a child with GS treated surgically with an alternative construct. STUDY DESIGN/SETTING: This is a case report and literature review. MATERIALS AND METHODS: Our case study involves a 5-year-old girl with a 6-month history of unresolved Fielding type II atlantoaxial subluxation caused by GS. Despite conservative treatment, the patient's symptoms continued to progress. After two failed closed reduction attempts, open reduction and C1-C2 fusion were performed with atlas laminar hook and axis pedicle polyaxial screws. A literature review of the surgical treatment of GS was also performed. RESULTS: After surgery, the patient exhibited full clinical and functional recovery with complete resolution of symptoms. At the 36-month follow up examination, there was continual evidence of satisfactory reduction and fusion. No complications were observed. Upon completion of the literature review, eight GS cases were found to have been treated surgically with the minimum patient age being 9 years. CONCLUSIONS: Conservative management of GS is the most common and effective treatment; however, a few surgical cases have been reported in the literature with good results. Satisfactory clinical results and fusion at 36 months post surgery were seen in a pediatric patient with atlantoaxial subluxation and instability using atlas laminar hook and axis pedicle polyaxial screws. PMID- 27669670 TI - Evaluation of American Society of Anesthesiologists classification as 30-day morbidity predictor after single-level elective anterior cervical discectomy and fusion. AB - BACKGROUND CONTEXT: Higher American Society of Anesthesiologists (ASA) classification is a known predictor of postoperative complication in diverse surgical settings. However, its predictive value is not established in single level elective anterior cervical discectomy and fusion (SLE-ACDF). PURPOSE: This study aimed to evaluate the predictive value of ASA classification system on 30 day morbidity following SLE-ACDF. DESIGN/SETTING: Patients who underwent SLE-ACDF between 2011 and 2013 were selected from the American College of Surgeons National Surgical Quality Improvement Program database. PATIENT SAMPLE: A total of 6,148 patients were selected from the 2011-2013 American College of Surgeons National Surgical Quality Improvement Program database. OUTCOME MEASURES: All outcomes are self-report measures as tracked by dedicated clinical reviewers via prospective review of inpatient charts, outpatient clinic visits, and direct contact with the surgical team. METHODS: Propensity score matching and multiple logistic regression analyses were performed to evaluate ASA classification as 30 day morbidity predictor. This study has no financial conflict and has no potential conflict of interest to disclose. RESULTS: A total of 6,148 patients were analyzed in this study. Patients in the ASA >II cohort had higher incidence of comorbidities and postoperative complications (overall complication, pneumonia, unplanned intubation, ventilator dependent >48 hours, cerebrovascular accident or stroke, catastrophic outcome, and airway complication). Propensity score matching yielded 1,628 pairs of well-matched patients. Multivariable analyses with the propensity score matched dataset revealed the following associations between ASA class >II and 30-day outcomes: any complication (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.48-1.41), pneumonia (OR 1.22, 95% CI 0.33-4.56), unplanned intubation (OR 1.49, 95% CI 0.41-5.36), ventilator >48 hours (OR 5.92, 95% CI 0.69-50.96), catastrophic outcome (OR 1.02, 95% CI 0.39 2.71), and airway complication (OR 2.21, 95% CI 0.67-7.29). CONCLUSIONS: Although we did not detect associations between ASA class >II and adverse 30-day outcomes following SLE-ACDF, imprecision of estimates precludes definitive inferences. Although ASA classification allows simple assessment of patients' physiological status, their overall perioperativerisk factors need to be considered collectively for adequate optimization and improved outcomes in SLE-ACDF. PMID- 27669671 TI - Preliminary analysis of the concurrent validity of the Spanish translation of the BEARS sleep screening tool for children. AB - : WHAT IS KNOWN ON THE SUBJECT?: Paediatric sleep problems are clinical conditions that often coexist with other mental health problems and meet criteria that warrant the implementation of screening procedures, including high prevalence, and significant clinical impact. Researchers have designed the BEARS, a user-friendly paediatric sleep screening tool that seems to increase the amount of sleep information recorded, as well as the likelihood of identifying sleep problems during routine health encounters. Nonetheless, there are no studies using the BEARS in Spanish-speaking samples. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Using a sample of children with mental health problems, this study provides support for the use of the Spanish version of the BEARS to identify the most common sleep problems seen in paediatric populations. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Considering how frequent sleep problems are, it is especially important for health professionals working with children in general, and with children with mental health problems in particular, to be aware of and be encouraged to use simple brief screening tools for paediatric sleep problems. ABSTRACT: Objective Research studies describe a high prevalence of sleep problems in children with mental health problems, up to 50%, and its role as a risk factor in the development of psychopathology. These often go unnoticed and are not evaluated in the clinical field. Our objective was to assess the concurrent validity of the BEARS, a brief paediatric sleep screening instrument, using the Children Sleep Habits Questionnaire (CSHQ) as the comparison instrument. Methods In this cross-sectional descriptive study, the BEARS was applied by a registered nurse to a sample of parents of children aged 2-16 years (n = 60, 71.7% male) who attended a mental healthcare facility (located in Murcia, Spain) for the first time to receive a group psychoeducational intervention. The association between the information collected with the BEARS and scores on the related subscales of the CSHQ was assessed by Mann-Whitney U tests. Results Children who, according to the BEARS, had a sleep problem obtained scores on the CSHQ-related subscales significantly higher than children who did not have a sleep problem (all Ps < 0.05). Conclusion Our results support the concurrent validity of the Spanish translation of the BEARS to detect sleep problems in paediatric nursing assessments. Further studies, with bigger and more heterogeneous samples, are warranted. PMID- 27669672 TI - Poorly differentiated squamous cell carcinoma of the cervix with sarcomatoid differentiation: Report of a case with cytohistological correlation. AB - Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix is a rare malignancy with uncertain pathogenesis and aggressive clinical behavior. The diagnosis of this tumor poses a challenge to the cytopathologist since accurate diagnosis is based on identification of two malignant components, that is, epithelial and sarcomatoid. Most cases usually lack the sarcomatoid component on Papanicolaou test (Pap test). Therefore, a poorly differentiated carcinoma or malignant neoplasm is the most often rendered diagnosis. To date, less than 20 cases have been reported. Most of these cases were diagnosed by histopathologic findings. To our knowledge, cytomorphologic findings of SSCC on a liquid-based Pap test, with utility of cell block sections, in recognition of the two components of tumor, with follow-up histopathologic correlation have not been described. A case of SSCC occurring in a 57-year-old postmenopausal woman, describing the cytologic features on a liquid-based Pap-test, histopathologic findings of subsequent cervical biopsy, differential diagnosis, and role of ancillary studies are illustrated and discussed. Diagn. Cytopathol. 2017;45:137 142. (c) 2016 Wiley Periodicals, Inc. PMID- 27669673 TI - Quantifying the biases in metagenome mining for realistic assessment of microbial ecology of naturally fermented foods. AB - Cultivation-independent investigation of microbial ecology is biased by the DNA extraction methods used. We aimed to quantify those biases by comparative analysis of the metagenome mined from four diverse naturally fermented foods (bamboo shoot, milk, fish, soybean) using eight different DNA extraction methods with different cell lysis principles. Our findings revealed that the enzymatic lysis yielded higher eubacterial and yeast metagenomic DNA from the food matrices compared to the widely used chemical and mechanical lysis principles. Further analysis of the bacterial community structure by Illumina MiSeq amplicon sequencing revealed a high recovery of lactic acid bacteria by the enzymatic lysis in all food types. However, Bacillaceae, Acetobacteraceae, Clostridiaceae and Proteobacteria were more abundantly recovered when mechanical and chemical lysis principles were applied. The biases generated due to the differential recovery of operational taxonomic units (OTUs) by different DNA extraction methods including DNA and PCR amplicons mix from different methods have been quantitatively demonstrated here. The different methods shared only 29.9-52.0% of the total OTUs recovered. Although similar comparative research has been performed on other ecological niches, this is the first in-depth investigation of quantifying the biases in metagenome mining from naturally fermented foods. PMID- 27669674 TI - Comparison of chronic mixture toxicity of nickel-zinc-copper and nickel-zinc copper-cadmium mixtures between Ceriodaphnia dubia and Pseudokirchneriella subcapitata. AB - Although aquatic organisms in the environment are exposed to mixtures of metals, risk assessment for metals is most commonly performed on a metal-by-metal basis. To increase the knowledge about chronic mixture effects, the authors investigated whether metal mixture effects are dependent on the biological species, mixture composition, and metal concentration ratio. The authors evaluated the effects of quaternary Ni-Zn-Cu-Cd and ternary Ni-Zn-Cu mixtures on 48-h algal growth rate (Pseudokirchneriella subcapitata) and 7-d daphnid reproduction (Ceriodaphnia dubia) using a ray design. Single metals were 3-fold to 42-fold more toxic for C. dubia than for P. subcapitata, based on the 50% effective concentration expressed as free metal activity, the range representing different metals. Statistical analysis of mixture effects showed that the ternary and quaternary mixture effects were antagonistic on algal growth relative to the concentration addition (CA) model, when the analysis was based on dissolved concentrations and on free metal ion activities. Using the independent action (IA) model, mixture effects in both rays were statistically noninteractive for algal growth when the analysis was based on dissolved concentrations; however, the interactions shifted toward antagonism when based on free ion activities. The ternary Ni-Zn-Cu mixture acted antagonistically on daphnid reproduction relative to both reference models, either expressed as free ion activities or dissolved concentrations. When Cd was added to the mixture, however, the mixture effects shifted toward noninteractivity for daphnids. The metal concentration ratio did not significantly influence the magnitude of observed antagonistic effects. Regardless of statistical interactions observed, based on the present study, CA and in most instances also IA can serve as a protective model for ternary Ni-Zn Cu and quaternary Ni-Zn-Cu-Cd toxicity to both species. Environ Toxicol Chem 2017;36:1056-1066. (c) 2016 SETAC. PMID- 27669675 TI - Continuous Consecutive Reactions with Inter-Reaction Solvent Exchange by Membrane Separation. AB - Pharmaceutical production typically involves multiple reaction steps with separations between successive reactions. Two processes which complicate the transition from batch to continuous operation in multistep synthesis are solvent exchange (especially high-boiling- to low-boiling-point solvent), and catalyst separation. Demonstrated here is membrane separation as an enabling platform for undertaking these processes during continuous operation. Two consecutive reactions are performed in different solvents, with catalyst separation and inter reaction solvent exchange achieved by continuous flow membrane units. A Heck coupling reaction is performed in N,N-dimethylformamide (DMF) in a continuous membrane reactor which retains the catalyst. The Heck reaction product undergoes solvent exchange in a counter-current membrane system where DMF is continuously replaced by ethanol. After exchange the product dissolved in ethanol passes through a column packed with an iron catalyst, and undergoes reduction (>99 % yield). PMID- 27669676 TI - High aspect ratio micro-explosions in the bulk of sapphire generated by femtosecond Bessel beams. AB - Femtosecond pulses provide an extreme degree of confinement of light matter interactions in high-bandgap materials because of the nonlinear nature of ionization. It was recognized very early on that a highly focused single pulse of only nanojoule energy could generate spherical voids in fused silica and sapphire crystal as the nanometric scale plasma generated has energy sufficient to compress the material around it and to generate new material phases. But the volumes of the nanometric void and of the compressed material are extremely small. Here we use single femtosecond pulses shaped into high-angle Bessel beams at microjoule energy, allowing for the creation of very high 100:1 aspect ratio voids in sapphire crystal, which is one of the hardest materials, twice as dense as glass. The void volume is 2 orders of magnitude higher than those created with Gaussian beams. Femtosecond and picosecond illumination regimes yield qualitatively different damage morphologies. These results open novel perspectives for laser processing and new materials synthesis by laser-induced compression. PMID- 27669677 TI - A preliminary study searching for the right dose of tacrolimus in very young (<=4 years) renal transplant patients. AB - OBJECTIVES: The Radboudumc Amalia Children's hospital in the Netherlands has a programme for renal transplantation in children aged <=4 years. Children receive chronic corticosteroid sparing immunosuppressive therapy that consists of tacrolimus and mycophenolate mofetil. This work aimed to describe the PK of tacrolimus in children <=4 years with renal transplants. METHODS: Paediatric renal transplant patients aged <=4 years were included in this analysis. A PK curve of tacrolimus recorded <=3 weeks after transplantation has been standard of care in our institution and aided in adjusting the dose in each patient to attain a target AUC0-12h of 210 MUg h/l early after transplantation. KEY FINDINGS: Eight patients were included. The first two patients received an initial twice-daily regimen and the subsequent six patients a three-times daily regimen. Median dose corrected AUCtau was 63 MUg h/l. AUC target attainment was 37.5%. Of the remaining patients, two had an AUC very close to (around 10% below) the target. CONCLUSIONS: Large interindividual variability of tacrolimus was observed and showed suboptimal AUC target attainment. In this population, an even more aggressive approach of higher doses (e.g. 0.4 mg/kg per day) and more early AUC determination should be considered. This should be evaluated prospectively in a larger group of patients. PMID- 27669678 TI - MR-based measurements and simulations of the magnetic field created by a realistic transcranial magnetic stimulation (TMS) coil and stimulator. AB - Transcranial magnetic stimulation (TMS) is an emerging technique that allows non invasive neurostimulation. However, the correct validation of electromagnetic models of typical TMS coils and the correct assessment of the incident TMS field (BTMS ) produced by standard TMS stimulators are still lacking. Such a validation can be performed by mapping BTMS produced by a realistic TMS setup. In this study, we show that MRI can provide precise quantification of the magnetic field produced by a realistic TMS coil and a clinically used TMS stimulator in the region in which neurostimulation occurs. Measurements of the phase accumulation created by TMS pulses applied during a tailored MR sequence were performed in a phantom. Dedicated hardware was developed to synchronize a typical, clinically used, TMS setup with a 3-T MR scanner. For comparison purposes, electromagnetic simulations of BTMS were performed. MR-based measurements allow the mapping and quantification of BTMS starting 2.5 cm from the TMS coil. For closer regions, the intra-voxel dephasing induced by BTMS prohibits TMS field measurements. For 1% TMS output, the maximum measured value was ~0.1 mT. Simulations reflect quantitatively the experimental data. These measurements can be used to validate electromagnetic models of TMS coils, to guide TMS coil positioning, and for dosimetry and quality assessment of concurrent TMS-MRI studies without the need for crude methods, such as motor threshold, for stimulation dose determination. PMID- 27669679 TI - A prognostic model for predicting urinary incontinence after robot-assisted radical prostatectomy. AB - BACKGROUND: The aim of this study is to develop a novel prognostic model for estimating the risk of postoperative urinary incontinence (UI) after robot assisted radical prostatectomy (RARP). METHODS: Participants comprised 131 men who underwent RARP at our hospital from 2011 to 2013. Cox regression analyses were performed to evaluate associations between UI and preoperative factors including filling cystometry and pressure-flow study results and magnetic resonance imaging. RESULTS: Logistic regression analyses revealed significant associations between membranous urethral length or levator thickness and UI at 3 and 6 months. Stratification produced high (membranous urethral length < 9.5 mm or levator thickness < 9.0 mm) and low (membranous urethral length >= 9.5 mm and levator thickness >= 9.0 mm) UI risk groups. These inter-group differences in UI rate were significant. CONCLUSIONS: We developed a novel prognostic model based on preoperative patient data that can be used for patient counselling. PMID- 27669680 TI - Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation. AB - BACKGROUND: Lubiprostone (8 MUg b.d.) received US Food and Drug Administration (FDA) approval in 2008 for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in women aged >=18 years. In 2012, the FDA issued new guidance for IBS-C clinical trials, recommending a composite endpoint incorporating both abdominal pain and stool frequency. AIM: In a post hoc analysis, similar criteria were applied to data from two pivotal, phase 3, double blind, randomised trials of lubiprostone in patients with IBS-C. METHODS: Included patients had a baseline spontaneous bowel movement (SBM) frequency <3/week and abdominal pain or bloating ratings >=1.36 on a 5-point scale [0 (absent) to 4 (very severe)]. Responders (composite endpoint) had a mean pain reduction >=30% compared with baseline, and an increase from baseline of >=1 SBM/week for >=6 of the 12 treatment weeks. Lubiprostone effects on abdominal pain alone were also evaluated, as were bloating alone and in a composite endpoint with stool frequency. RESULTS: In pooled data, 325 patients received lubiprostone and 180 received placebo. Rates of response were higher with lubiprostone vs. placebo for the composite endpoint of improved pain and stool frequency (26.3% vs. 15.3%, respectively; P = 0.008) and the composite endpoint of improved bloating and stool frequency (23.8% vs. 12.6%, respectively; P = 0.012). Response rates were also higher with lubiprostone vs. placebo for abdominal pain alone (P = 0.005) and bloating alone (P = 0.012). CONCLUSION: Lubiprostone was significantly more effective than placebo in improving abdominal pain or bloating, and also in composite endpoints that included stool frequency. PMID- 27669681 TI - Naturally occurring compounds acting as potent anti-metastatic agents and their suppressing effects on Hedgehog and WNT/beta-catenin signalling pathways. AB - Despite numerous remarkable achievements in the field of anti-cancer therapy, tumour relapse and metastasis still remain major obstacles in improvement of overall cancer survival, which may be at least partially owing to epithelial mesenchymal transition (EMT). Multiple signalling pathways have been identified in EMT; however, it appears that the role of the Hedgehog and WNT/beta-catenin pathways are more prominent than others. These are well-known preserved intracellular regulatory pathways of different cellular functions including proliferation, survival, adhesion and differentiation. Over the last few decades, several naturally occurring compounds have been identified to significantly obstruct several intermediates in Hedgehog and WNT/beta-catenin signalling, eventually resulting in suppression of signal transduction. This article highlights the current state of knowledge associated with Hedgehog and WNT/beta catenin, their involvement in metastasis through EMT processes and introduction of the most potent naturally occurring agents with capability of suppressing them, eventually overcoming tumour relapse, invasion and metastasis. PMID- 27669683 TI - Woody climbers show greater population genetic differentiation than trees: Insights into the link between ecological traits and diversification. AB - The climbing habit is a key innovation in plants: climbing taxa have higher species richness than nonclimbing sister groups. We evaluated the hypothesis that climbing plant species show greater among-population genetic differentiation than nonclimber species. We compared the among-population genetic distance in woody climbers (eight species, 30 populations) and trees (seven species, 29 populations) coexisting in nine communities in a temperate rainforest. We also compared within-population genetic diversity in co-occurring woody climbers and trees in two communities. Mean genetic distance between populations of climbers was twice that of trees. Isolation by distance (increase in genetic distance with geographic distance) was greater for climbers. Climbers and trees showed similar within-population genetic diversity. Our longevity estimate suggested that climbers had shorter generation times, while other biological features often associated with diversification (dispersal and pollination syndromes, mating system, size, and metabolic rate) did not show significant differences between groups. We hypothesize that the greater population differentiation in climbers could result from greater evolutionary responses to local selection acting on initially higher within-population genetic diversity, which could be driven by neutral processes associated with shorter generation times. Increased population genetic differentiation could be incorporated as another line of evidence when testing for key innovations. PMID- 27669682 TI - How best to use and evaluate Patient Information Leaflets given during a consultation: a systematic review of literature reviews. AB - BACKGROUND: In the past, several authors have attempted to review randomized clinical trials (RCT) evaluating the impact of Patient Information Leaflets (PILs) used during a consultation and draw some general conclusions. However, this proved difficult because the clinical situations, size and quality of RCTs were too heterogeneous to pool relevant data. OBJECTIVE: To overcome this 30-year stalemate, we performed a review of reviews and propose general recommendations and suggestions for improving the quality of PILs, how to use them and methods for evaluating them. METHODOLOGY: We searched five databases for reviews, systematic reviews and meta-analyses describing PILs. We drew general and condition-linked conclusions concerning the impact of PILs. Checklists summarize criteria for quality PILs, and ways of using and evaluating them. RESULTS: Of 986 articles found, 24 reviews were pertinent; the five oldest considered the impact of PILs irrespective of the condition the patient consulted for; the 19 more recent ones mostly addressed precise clinical situations. DISCUSSION: Whatever the clinical situation, PILs improve patients' knowledge and satisfaction. For acute conditions, in the short-term PILs also improve adherence to treatment. For chronic diseases, invasive procedures or screening situations, their impact on adherence varies depending on the context, how the PILs are given and the invasiveness of the intervention. CONCLUSION: PILs are considered to be very useful, especially for acute conditions where the patient is the first to suffer from lack of information. We propose checklists for writing, designing, using and evaluating PILs in RCTs to enable comparisons between different studies. PMID- 27669684 TI - Direct and label-free detection of the human growth hormone in urine by an ultrasensitive bimodal waveguide biosensor. AB - A label-free interferometric transducer showing a theoretical detection limit for homogeneous sensing of 5 * 10-8 RIU, being equivalent to a protein mass coverage resolution of 2.8 fg mm-2 , is used to develop a high sensitive biosensor for protein detection. The extreme sensitivity of this transducer combined with a selective bioreceptor layer enables the direct evaluation of the human growth hormone (hGH) in undiluted urine matrix in the 10 pg mL-1 range. PMID- 27669685 TI - Low prevalence of Kingella kingae carriage in children aged 6-48 months in Sydney, Australia. AB - AIM: A prospective observational study was conducted to estimate the prevalence of oropharyngeal carriage of Kingella kingae in healthy Australian pre-school children. METHODS: Screening for carriage of K. kingae as well as Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae, and K. kingae was undertaken using a single bacterial throat swab taken from well children aged 6 months to 4 years. Standard laboratory procedures were used for culture and identification of organisms. RESULTS: One hundred children were enrolled between October and December 2014 at the Children's Hospital at Westmead. Median age was 24.0 months (range 6.1-48.8 months); 52 children were male and 36 attended day-care facilities. Forty-one children had siblings aged less than 5 years and 67 children had siblings of any age. K. kingae oropharyngeal carriage was not detected in any of the children. Rates of carriage of other organisms were: 30% S. aureus, 21% H. influenzae, 2% S. pneumoniae and 2% S. pyogenes. Thirty-eight children were colonised with Kingella denitrificans. CONCLUSIONS: Our results suggest that prevalence of K. kingae carriage in pre-school children in Sydney is very low and support local and national guidelines that recommend flucloxacillin as empiric first-line therapy for children with osteoarticular infections. Studies conducted over the winter months and in other Australian centres could help answer outstanding questions regarding differences in carriage rates of K. kingae in children. PMID- 27669686 TI - Penetration of CdSe/ZnS quantum dots into differentiated vs undifferentiated Caco 2 cells. AB - BACKGROUND: Quantum dots (QDs) have great potential as fluorescent labels but cytotoxicity relating to extra- and intracellular degradation in biological systems has to be addressed prior to biomedical applications. In this study, human intestinal cells (Caco-2) grown on transwell membranes were used to study penetration depth, intracellular localization, translocation and cytotoxicity of CdSe/ZnS QDs with amino and carboxyl surface modifications. The focus of this study was to compare the penetration depth of QDs in differentiated vs undifferentiated cells using confocal microscopy and image processing. RESULTS: Caco-2 cells were exposed to QDs with amino (NH2) and carboxyl (COOH) surface groups for 3 days using a concentration of 45 ug cadmium ml-1. Image analysis of confocal/multiphoton microscopy z-stacks revealed no penetration of QDs into the cell lumen of differentiated Caco-2 cells. Interestingly, translocation of cadmium ions onto the basolateral side of differentiated monolayers was observed using high resolution inductively coupled plasma mass spectrometry (ICP-MS). Membrane damage was neither detected after short nor long term incubation in Caco 2 cells. On the other hand, intracellular localization of QDs after exposure to undifferentiated cells was observed and QDs were partially located within lysosomes. CONCLUSIONS: In differentiated Caco-2 monolayers, representing a model for small intestinal enterocytes, no penetration of amino and carboxyl functionalized CdSe/ZnS QDs into the cell lumen was detected using microscopy analysis and image processing. In contrast, translocation of cadmium ions onto the basolateral side could be detected using ICP-MS. However, even after long term incubation, the integrity of the cell monolayer was not impaired and no cytotoxic effects could be detected. In undifferentiated Caco-2 cells, both QD modifications could be found in the cell lumen. Only to some extend, QDs were localized in endosomes or lysosomes in these cells. The results indicate that the differentiation status of Caco-2 cells is an important factor in internalization and localization studies using Caco-2 cells. Furthermore, a combination of microscopy analysis and sensitive detection techniques like ICP-MS are necessary for studying the interaction of cadmium containing QDs with cells. PMID- 27669687 TI - An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model. AB - BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22-24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy. METHODS: In this study, the experiments were designed including prevention and therapeutic stages in order to attain effect against tumor recurrence in clinical settings. The anti tumor efficacy of a novel cytokine adjuvant vaccine that contained cytokines GM CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse tumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the expression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow cytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and the lactic dehydrogenates (LDH) release assays. IFN-gamma, IL-2 and GM-CSF secretion in serum was assayed by ELISA. RESULTS: Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended the survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were significantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells play a key role in anti-tumor response. CONCLUSIONS: The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response and represented a promising immunotherapeutic approach for patients with colon cancer. PMID- 27669688 TI - Fluorouracil implants caused a diaphragmatic tumor to be misdiagnosed as liver metastasis: a case report. AB - BACKGROUND: Fluorouracil implants are widely used in peritoneal interstitial chemotherapy. Curative effects have been obtained, but implants have also caused some complications. CASE PRESENTATION: We performed an analysis of a 66-year-old male patient's case history, as well as conventional pathological analysis and Raman spectroscopic detection of the diaphragmatic tumor. We also analyzed the underlying causes of this condition to prevent complications and reduce misdiagnoses in future cases. The patient had a history of peritoneal fluorouracil implantation. Pathological analysis of the diaphragmatic mass revealed foreign particles, and Raman detection showed that the mass contained fluorouracil. CONCLUSION: Fluorouracil implants may persist due to the high concentrations of this drug used in peritoneal chemotherapy. This finding should provide guidance and improve the application of peritoneal implants. In clinical trials, and the diagnosis of liver metastasis should be based on pathological results. PMID- 27669690 TI - Autologous bone grafts with MSCs or FGF-2 accelerate bone union in large bone defects. AB - BACGROUND: Although the contribution of fibroblast growth factor (FGF)-2 and mesenchymal stromal cells (MSCs) to bone formation is well known, few studies have investigated the combination of an autologous bone graft with FGF-2 or MSCs for large bone defects. METHODS: We studied an atrophic non-union model with a large bone defect, created by resecting a 10-mm section from the center of each femoral shaft of 12-week-old Sprague-Dawley rats. The periosteum of the proximal and distal ends of the femur was cauterized circumferentially, and excised portions were used in the contralateral femur as autologous bone grafts. The rats were randomized to three groups and given no further treatment (group A), administered FGF-2 at 20 MUg/20 MUL (group B), or 1.0 * 106 MSCs (group C). Radiographs were taken every 2 weeks up to 12 weeks, with CT performed at 12 weeks. Harvested femurs were stained with toluidine blue and evaluated using radiographic and histology scores. RESULTS: Radiographic and histological evaluation showed that bone union had been achieved at 12 weeks in group C, while group B showed callus formation and bridging callus but non-union, and in group A, callus formation alone was evident. Both radiographic and histological scores were significantly higher at 2, 4, 6, 8, 10, and 12 weeks in groups B and C than group A and also significantly higher in group C than group B at 12 weeks. CONCLUSIONS: These data suggest that autologous bone grafts in combination with MSCs benefit difficult cases which cannot be treated with autologous bone grafts alone. PMID- 27669689 TI - Metamizole versus ibuprofen at home after day surgery: study protocol for a randomised controlled trial. AB - BACKGROUND: Postoperative pain and, in a more extended perspective, quality of recovery (QOR) should be considered the principal endpoints after day surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are a cornerstone of pain treatment after painful day surgery. Nevertheless, NSAIDs are not always sufficiently effective, have numerous contraindications, and consequently are not suitable in up to 25 % of all patients. Metamizole is a non-opioid compound with a favourable gastrointestinal, cardiovascular and cerebrovascular profile compared to NSAIDs. The aim of this study is to assess if a combination of metamizole and paracetamol is non-inferior to a combination of ibuprofen and paracetamol in the treatment of acute postoperative pain at home after painful day case surgery. In addition, we aim to assess and compare quality of recovery (QOR) profiles of both groups. METHODS/DESIGN: This is an investigator-initiated, double-blind, randomised controlled, non-inferiority trial. A total of 200 patients undergoing elective haemorrhoid surgery, arthroscopic shoulder or knee surgery, or inguinal hernia repair in a day care setting will be randomised to receive either a combination of metamizole and paracetamol (MP) or a combination of ibuprofen and paracetamol (IP). Participants will take study medication orally for 4 days. Primary endpoints are average postoperative pain intensity measured by an 11-point Numeric Rating Scale at postoperative day 1 and QOR profile measured by the Functional Recovery Index (FRI), the 1-item Global Surgical Recovery (GSR) index and the EuroQol (EQ-5D) questionnaire at days 1, 2, 3, 4, 7, 14 and 28 postoperatively. Secondary outcomes include compliance with study medication, adverse effects of study medication, use of rescue medication and satisfaction with study medication, surgery and hospital care and telephone follow-up. DISCUSSION: This study will provide clinical evidence on the analgesic efficacy and safety of a combination of metamizole and paracetamol in treating postoperative pain at home after painful day surgery. This study may also provide an insight into QOR profile after four different types of surgery and into the interrelationship between three different instruments used to assess QOR. TRIAL STATUS: Recruitment is currently ongoing. TRIAL REGISTRATION: European Union Clinical Trials Register 2015-003987-35 . Registered 10 November 2015. PMID- 27669692 TI - Profilin1 biology and its mutation, actin(g) in disease. AB - Profilins were discovered in the 1970s and were extensively studied for their significant physiological roles. Profilin1 is the most prominent isoform and has drawn special attention due to its role in the cytoskeleton, cell signaling, and its link to conditions such as cancer and vascular hypertrophy. Recently, multiple mutations in the profilin1 gene were linked to amyotrophic lateral sclerosis (ALS). In this review, we will discuss the physiological and pathological roles of profilin1. We will further highlight the cytoskeletal function and dysfunction caused by profilin1 dysregulation. Finally, we will discuss the implications of mutant profilin1 in various diseases with an emphasis on its contribution to the pathogenesis of ALS. PMID- 27669691 TI - Assessing heterogeneity in oligomeric AAA+ machines. AB - ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors. PMID- 27669693 TI - Mechanisms of ciliogenesis suppression in dividing cells. AB - The primary cilium is a non-motile and microtubule-enriched protrusion ensheathed by plasma membrane. Primary cilia function as mechano/chemosensors and signaling hubs and their disorders predispose to a wide spectrum of human diseases. Most types of cells assemble their primary cilia in response to cellular quiescence, whereas they start to retract the primary cilia upon cell-cycle reentry. The retardation of ciliary resorption process has been shown to delay cell-cycle progression to the S or M phase after cell-cycle reentry. Apart from this conventional concept of ciliary disassembly linked to cell-cycle reentry, recent studies have led to a novel concept, suggesting that cells can suppress primary cilia assembly during cell proliferation. Accumulating evidence has also demonstrated the importance of Aurora-A (a protein originally identified as one of mitotic kinases) not only in ciliary resorption after cell-cycle reentry but also in the suppression of ciliogenesis in proliferating cells, whereas Aurora-A activators are clearly distinct in both phenomena. Here, we summarize the current knowledge of how cycling cells suppress ciliogenesis and compare it with mechanisms underlying ciliary resorption after cell-cycle reentry. We also discuss a reciprocal relationship between primary cilia and cell proliferation. PMID- 27669694 TI - Production of human type II collagen using an efficient baculovirus-silkworm multigene expression system. AB - Human type II collagen is a macromolecular protein found throughout the human body. The baculovirus expression vector system is one of the most ideal systems for the routine production and display of recombinant eukaryotic proteins in insect, larvae, and mammalian cells. We use this system to express a full-length gene, human type II collagen cDNA (4257 bp), in cultured Spodoptera frugiperda 9 cells (Sf9), Bombyx mori cells, and silkworm larvae. In this study, the expression of human type II collagen gene in both insect cells and silkworm larvae was purified by nickel column chromatography, leading to 300-kDa bands in SDS-PAGE and western blotting indicative of collagen alpha-chains organized in a triple-helical structure. About 1 mg/larva human type II collagen is purified from silkworm skin, which shows a putative large scale of collagen production way. An activity assay of recombinant human type II collagen expressed by silkworm larvae demonstrated that the recombinant protein has considerable bioactive properties. Scanning electron microscopy of purified proteins clearly reveals randomly distributed and pitted structures. We conclude that the baculovirus-silkworm multigene expression system can be used as an efficient platform for express active human type II collagen and other complicated eukaryotic proteins. PMID- 27669696 TI - Neurofibroma of the cervical spine in infants. PMID- 27669695 TI - Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. PMID- 27669697 TI - Percutaneous extrapedicular vertebroplasty with expandable intravertebral implant in compression vertebral body fracture in pediatric patient-technical note. AB - PURPOSE: The aim of the article is to present the new extrapedicular percutaneous technique for posttraumatic vertebral column fracture. METHODS: A 15-year-old boy needed a surgical Th8 posttraumatic vertebral body (VB) compressive fracture reduction due to insufficient conservative treatment and consistent severe clinical symptoms. After 6 months of external Jevett long-roll brace stabilization, progressive sagittal balance disturbance of thoracic kyphosis was measured and persistent clinical symptoms were observed. It was decided to present a surgical technique method allowing to attempt to reduce VB fracture, rebalance the vertebral column (VC) without any motion limitation, and decrease clinical symptoms. The procedure was performed percutaneously from extrapedicular approach with intravertebral implant (Spine Jack(r)-VeximTM) and cement (Interface(r)-VeximTM) under fluoroscopic imaging (ZiehmTM 8000(r)). RESULTS: The whole procedure was uneventful. Now, the child is free from clinical symptoms and the partial reduction of VB fracture was achieved. The patient has been followed for 3 months. In the control CT scans, the VB fracture reduction is stable and no progression of thoracic kyphosis angle is observed. Furthermore since the surgical procedure, the patient is clinical symptom free. CONCLUSION: The extrapedicular percutaneus technique of VB fracture reduction with intravertebral fixation allowed to partially reduce the VB compressive fracture, rebalance the VC without any motion limitation, avoid external long-roll brace, and eliminate clinical symptoms. The procedure is minimally invasive, fast, and clinically effective. However, the technique should be restricted only to carefully selected clinical cases. PMID- 27669698 TI - Congenital craniopharyngioma treated by radical surgery: case report and review of the literature. AB - PURPOSE: Craniopharyngiomas are 5-10 % of all pediatric tumors, but are seldomly encountered in the perinatal period. Only seven instances of a truly antenatal diagnosis of a congenital craniopharyngioma that subsequently underwent radical surgery have been reported. We present the case of a patient who received the diagnosis of a suprasellar tumor during the prenatal period and received radical surgery. METHODS: We report a case of a neonatal craniopharyngioma treated surgically. RESULTS: The pregnancy progressed uneventfully until a routine ultrasound at 37 weeks of gestation showed a 15 * 15 mm high echoic mass in the center of the fetal head. Neonatal Gd-enhanced T1-weighted MRI at 5 days of life showed a homogenously enhanced mass (16*22*15 mm) in the sellar and suprasellar lesion. As the tumor showed rapid growth at the 3rd month of life, the patient underwent a surgical treatment and the mass was totally removed. Three years later, the physical and mental development of the patient was normal, and Gd-MRI studies showed no tumor recurrence. CONCLUSION: The present case is the eighth case of a truly antenatal diagnosis of a craniopharyngioma that underwent successful radical surgery. Craniopharyngioma is a benign tumor and thought to be a slow growing tumor in childhood. The results of radical surgery were very poor, and the mortality and morbidity rates were high in the previous reports due to the huge size of tumor at operation. The present case demonstrated the rapid growth in short interval of Gd-MRI. This is the first report of tumor kinetics of congenital craniopharyngioma with previous reports. The calculated tumor doubling time in our case was 37 days. PMID- 27669699 TI - A program evaluation of Kids2Hear, a student-run hearing screening program for school children. AB - BACKGROUND: Hearing deficits in children are demonstrably negatively associated with language acquisition and cognition. Although universal neonatal hearing screening exists, it is not offered equally across Canada. Additionally, children emigrating from other countries are often not assessed. The objective of this study is to evaluate Kids2Hear, a free hearing screening program run by medical students at elementary schools, and to determine the rate of hearing deficits that were identified and referred for evaluation. METHODS: Retrospective analysis of screening program data from 228 participants seen at three inner-city elementary schools over six months. RESULTS: In our sample, the mean age was 5.8 +/- 1.0 years with 48 % males. Approximately 21 participants (9.3 %) were screened positive for a hearing deficit and required referral for supplementary audiological evaluation. About 44 participants (19.3 %) were referred to a family physician for otoscopic abnormalities. Females were significantly more likely to be identified for both hearing deficits and otoscopic abnormalities. CONCLUSIONS: Hearing deficits and otoscopic abnormalities are common among young children. Female children may be at higher risk for developing hearing issues or otoscopic abnormalities compared to males. Additional research is needed to determine the effectiveness of hearing screening programs. PMID- 27669700 TI - Behaviour of two typical stents towards a new stent evolution. AB - This study explores the analysis of a new stent geometry from two typical stents used to treat the coronary artery disease. Two different finite element methods are applied with different boundary conditions to investigate the stenosis region. Computational fluid dynamics (CFD) models including fluid-structure interaction are used to assess the haemodynamic impact of two types of coronary stents implantation: (1) type 1-based on a strut-link stent geometry and (2) type 2-a continuous helical stent. Using data from a recent clinical stenosis, flow disturbances and consequent shear stress alterations introduced by the stent treatment are investigated. A relationship between stenosis and the induced flow fields for the two types of stent designs is analysed as well as the correlation between haemodynamics and vessel wall biomechanical factors during the initiation and development of stenosis formation in the coronary artery. Both stents exhibit a good performance in reducing the obstruction artery. However, stent type 1 presents higher radial deformation than the type 2. This deformation can be seen as a limitation with a long-term clinical impact. PMID- 27669701 TI - A new method to approximate load-displacement relationships of spinal motion segments for patient-specific multi-body models of scoliotic spine. AB - Load-displacement relationships of spinal motion segments are crucial factors in characterizing the stiffness of scoliotic spine models to mimic the spine responses to loads. Although nonlinear approach to approximation of the relationships can be superior to linear ones, little mention has been made to deriving personalized nonlinear load-displacement relationships in previous studies. A method is developed for nonlinear approximation of load-displacement relationships of spinal motion segments to assist characterizing in vivo the stiffness of spine models. We propose approximation by tangent functions and focus on rotational displacements in lateral direction. The tangent functions are characterized using lateral bending test. A multi-body model was characterized to 18 patients and utilized to simulate four spine positions; right bending, left bending, neutral, and traction. The same was done using linear functions to assess the performance of the proposed tangent function in comparison with the linear function. Root-mean-square error (RMSE) of the displacements estimated by the tangent functions was 44 % smaller than the linear functions. This shows the ability of our tangent function in approximation of the relationships for a range of infinitesimal to large displacements involved in the spine movement to the four positions. In addition, the models based on the tangent functions yielded 67, 55, and 39 % smaller RMSEs of Ferguson angles, locations of vertebrae, and orientations of vertebrae, respectively, implying better estimates of spine responses to loads. Overall, it can be concluded that our method for approximating load-displacement relationships of spinal motion segments can offer good estimates of scoliotic spine stiffness. PMID- 27669703 TI - Nearly one in 10 premature babies did not have a temperature check in first hour after birth, UK audit finds. PMID- 27669702 TI - Discrimination of numerical proportions: A comparison of binomial and Gaussian models. AB - Observers discriminated the numerical proportion of two sets of elements (N = 9, 13, 33, and 65) that differed either by color or orientation. According to the standard Thurstonian approach, the accuracy of proportion discrimination is determined by irreducible noise in the nervous system that stochastically transforms the number of presented visual elements onto a continuum of psychological states representing numerosity. As an alternative to this customary approach, we propose a Thurstonian-binomial model, which assumes discrete perceptual states, each of which is associated with a certain visual element. It is shown that the probability beta with which each visual element can be noticed and registered by the perceptual system can explain data of numerical proportion discrimination at least as well as the continuous Thurstonian-Gaussian model, and better, if the greater parsimony of the Thurstonian-binomial model is taken into account using AIC model selection. We conclude that Gaussian and binomial models represent two different fundamental principles-internal noise vs. using only a fraction of available information-which are both plausible descriptions of visual perception. PMID- 27669705 TI - Lung Cancer Epidemiology in Korea. AB - PURPOSE: The current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea. MATERIALS AND METHODS: Lung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated. RESULTS: Although the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups. CONCLUSION: The epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes. PMID- 27669704 TI - Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer. AB - PURPOSE: This study was conducted to evaluate the prognostic significance of pre treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). RESULTS: In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. CONCLUSION: Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID- 27669706 TI - Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer. AB - PURPOSE: This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer. MATERIALS AND METHODS: The expression of V ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively. RESULTS: Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05). CONCLUSION: V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells. PMID- 27669707 TI - Vouchers: A Hot Ticket for Reaching the Poor and Other Special Groups With Voluntary Family Planning Services. PMID- 27669709 TI - Inflections of the Bayesian Paradigm in Perceptual Psychology. AB - Bayesian modeling has gained a conspicuous position in contemporary perceptual psychology. It can be examined from two viewpoints: a formal one, concerning the logical attributes of and the algebraic operations on the components of the models, and a substantive one, concerning the empirical meaning of those components. We maintain that, while there is homogeneity between Bayesian models of visual perception in their formal setup, remarkable differences can be found in their substantive aspect, that is, how the question "Where do probabilities come from?" is answered when designing the models. In particular, we focus on an inflection that we call "congenial" because it consistently embodies the inversion idea of the Bayes' rule in terms of optical inversion and highlight delicate issues that face this inflection for a consistent realization of the scientific program it represents. We also suggest ideas concerning the organization of the Bayesian area within perceptual psychology, which appears variegated, with the congenial inflection in a central position, and a fringe of disputable classification along the border. PMID- 27669708 TI - Persistent fifth arch anomalies - broadening the spectrum to include a variation of double aortic arch vascular ring. AB - Fifth arch anomalies are rare and complex and frequently misdiagnosed or mistaken for other entities. We report a double arch vascular ring that is thought to consist of right fourth arch and left fifth arch components, a previously undescribed persistent fifth arch variant. The currently recognized spectrum and classification of fifth arch vascular anomalies are expanded along with illustrative images to justify the proposed changes. Reviewing and expanding the classification of fifth arch anomalies to include a double arch ring variant will promote recognition, correct diagnosis and appropriate management of these anomalies. PMID- 27669710 TI - Commentary on "Transanal total mesorectal excision (taTME) for rectal cancer: a systematic review and meta-analysis of oncological and perioperative outcomes compared with laparoscopic total mesorectal excision", published in BMC Cancer 2016 Jul 4;16(1):380. doi:10.1186/s12885-016-2428-5. PMID- 27669711 TI - Short-term outcomes of a novel endoscopic clipping device for closure of the internal opening in 100 anorectal fistulas. AB - BACKGROUND: One hundred consecutive applications of a new clipping device, the OTSC(r) Proctology (Ovesco Endoscopy AG), were analyzed to assess its efficacy for the treatment of complex anorectal fistulas. METHODS: In patients with anorectal fistulas, minimally invasive surgery with the OTSC(r) Proctology system was performed according to a standardized technique: the fistula tract was debrided using a special fistula brush, and the clip was applied on the internal fistula opening. In some of the patients, postoperative pain was evaluated using a visual analog scale. After 6 months, the postoperative clinical course and the fistula healing were assessed. RESULTS: A total of 100 OTSC(r) Proctology procedures were performed in 96 patients with 55 transsphincteric, 38 suprasphincteric, 2 extrasphincteric, and 5 rectovaginal fistulas. In all but 11 fistulas (8 Crohn's disease, 3 ulcerative colitis), the fistulas were of cryptoglandular origin. The median operation time was 32 min (range 17-66 min). There were no major intraoperative technical problems. All patients found the postoperative pain to be tolerable with standard pain medication. The short-term results of 99 clip applications were analyzed: the healing rate for first-line fistula therapy was 79 %, whereas in recurrent fistulas, the success rate was 26 %. OTSC(r) Proctology was successful in 45 % of fistulas associated with inflammatory bowel disease and in 20 % of rectovaginal fistulas. CONCLUSIONS: OTSC(r) Proctology provides convincing results as first-line treatment for complex cryptoglandular fistulas. It is a safe, effective, minimally invasive, and sphincter-sparing procedure with postoperative pain comparable to other types of fistula surgery. PMID- 27669712 TI - Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. AB - OBJECTIVES: Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. METHODS: Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP 2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis. RESULTS: The serum level of patients (IL-18) increased significantly with the grade of IVD degeneration. There was a dramatic alteration in IL-18 level between the advanced degeneration (Grade III to V) group and the normal group (p = 0.008) Furthermore, IL-18 induced upregulation of the catabolic regulator MMP13 and downregulation of the anabolic regulators aggrecan, type II collagen, and SOX6 at 24 hours, contributing to degradation of disc matrix enzymes. However, BMP-2 antagonised the IL-18 induced upregulation of aggrecan, type II collagen, and SOX6, resulting in reversal of IL-18 mediated disc degeneration. CONCLUSIONS: BMP-2 is anti catabolic in human NP and AF cells, and its effects are partially mediated through provocation of the catabolic effect of IL-18. These findings indicate that BMP-2 may be a unique therapeutic option for prevention and reversal of disc degeneration.Cite this article: S. Ye, B. Ju, H. Wang, K-B. Lee. Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. Bone Joint Res 2016;5:412-418. DOI: 10.1302/2046-3758.59.BJR-2016 0032.R1. PMID- 27669713 TI - Health insurance coverage, neonatal mortality and caesarean section deliveries: an analysis of vital registration data in Colombia. AB - BACKGROUND: Low-income and middle-income countries have introduced different health insurance schemes over the past decades, but whether different schemes are associated with different neonatal outcomes is yet unknown. We examined the association between the health insurance coverage scheme and neonatal mortality in Colombia. METHODS: We used Colombian national vital registration data, including all live births (2 506 920) and neonatal deaths (17 712) between 2008 and 2011. We used Poisson regression models to examine the association between health insurance coverage and the neonatal mortality rate (NMR), distinguishing between women insured via the contributory scheme (40% of births, financed through payroll and employer's contributions), government subsidised insurance (47%) and the uninsured (11%). RESULTS: NMR was lower among babies born to mothers in the contributory scheme (6.13/1000) than in the subsidised scheme (7.69/1000) or the uninsured (8.38/1000). Controlling for socioeconomic and demographic factors, NMRs remained higher for those in the subsidised scheme (OR 1.09, 95% CI 1.05 to 1.14) and the uninsured (OR 1.16, 95% CI 1.10 to 1.23) compared to those in the contributory scheme. These differences increased in models that additionally controlled for caesarean section (C-section) delivery. This increase was due to the higher fraction of C-section deliveries among women in the contributory scheme (49%, compared to 34% for the subsidised scheme and 28% for the uninsured). CONCLUSIONS: Health insurance through the contributory system is associated with lower neonatal mortality than insurance through the subsidised system or lack of insurance. Universal health insurance may not be sufficient to close the gap in newborn mortality between socioeconomic groups. PMID- 27669714 TI - Demirjian's method is unsuitable for dental age estimation. PMID- 27669715 TI - Validation of ultraviolet, infrared, and narrow band light alternate light sources for detection of bruises in a pigskin model. AB - Alternate light sources such as ultraviolet, narrow band, and infrared have been used in an attempt to reveal the presence of bruising that is not otherwise apparent (inapparent). The following study evaluates the ability of alternate light sources to enhance visibility of bruises by employing an objective assessment of digital photography images in conjunction with histology. A pigskin model was employed with bruises created by injection of blood to be not visible or barely visible (inapparent) under white light. The pigskin was photographed using alternate light source illumination. Images were assessed using the program Fiji(r) to measure enhancement in terms of bruise length (cm). Photography results were compared with histology to confirm the presence of bruising. Violet and blue light sources produced the greatest enhancement, both with a p < 0.0001. Regions that were not bruises were also enhanced with light sources in this study, indicating that light sources are not specific, and that their use to enhance the visibility of bruising should be undertaken with caution. PMID- 27669716 TI - PCSK9: the Critical Role of Familial Hypercholesterolemia from Discovery to Benefit for all : Editorial to: "Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/Dl or Higher" by Henry N. Ginsberg et Al. PMID- 27669718 TI - Healthcare Disparities in Hispanic Diabetes Care: A Propensity Score-Matched Study. AB - Hispanics represent the largest minority group in the US. Research has shown that the ethnic minority especially Hispanics have a disproportionate burden of illness associated with diabetes mellitus. However, many have been focused on small sample sizes with potential selection bias. This study aims to examine the ethnicity disparity in health care utilization and expenditures between Hispanic and non-Hispanics after controlling for confounding variables. Cross-sectional with propensity score-matched design. The study revealed that Hispanics with diabetes had higher poverty rates, lower education, less physical activity, and less health care utilization/expenditures than did non-Hispanics. The assessment of ethnicity differences in health care is challenging because of the potential biases that require careful adjustment. This study successfully identified and controlled for confounding bias and concluded the Hispanics disparity in health care utilization still exists. PMID- 27669717 TI - Relationship Between Negative Mood and Health Behaviors in an Immigrant and Refugee Population. AB - Immigrants experience an escalation of negative health behaviors after arrival to the United States. Negative mood is associated with poorer health behaviors in the general population; however, this relationship is understudied in immigrant populations. Adolescent (n = 81) and adult (n = 70) participants completed a health behavior survey for immigrant families using a community-based participatory research approach. Data was collected for mood, nutrition, and physical activity. Adolescents with positive mood drank less regular soda, and demonstrated more minutes, higher levels, and greater social support for physical activity (all ps < .05). Adults with positive mood reported more snacking on fruits/vegetables, greater self-efficacy for physical activity, and better physical well-being (all ps < .05). Negative mood was associated with low physical activity level and poor nutritional habits in adolescent and adult immigrants. Designing community-based programs offering strategies for mood management and healthy lifestyle change may be efficacious for immigrant populations. PMID- 27669719 TI - A Representative Study of Deaths of North Indian Migrants and Its Medical Certification Across the World. AB - Many Indians is moving to other nations of the world in the search of employment, education or other reasons. The process of globalization along with the faster mode of traveling and communication has facilitated this movement in the hope of getting more opportunities and earning of easy money abroad, than in India. Unfortunately, sometimes they meet a tragic end and their families in India get only their dead bodies back from abroad. This study focuses on these kind of unfortunate tragic events faced by Indians in different countries and thereby raise a concern on their safety abroad and necessitate the need of relooking in to the quality of medical certification of death and medico legal investigations to find out the real reasons of deaths to avoid any kind of doubt in mind. Data was collected from medical death certificates and passports of the deceased Indians. There was a total of 711 dead bodies/human remains received in 2012 at IGI airport New Delhi. The Middle East countries together contributed a total of 398 (55.98 %) cases. The distribution as per manner of death shows that in maximum number of cases (269), the manner of death was ambiguous with unspecified aetiology. The study therefore recommends for upgradation of the level of medico legal investigations in form of 2nd autopsy in recipient country and proper medical death certification. PMID- 27669720 TI - Evaluation of the periodontal conditions of teeth with restored and non-restored non-carious cervical lesions. AB - OBJECTIVE: This research evaluated the periodontal conditions of teeth with restored and non-restored non-carious cervical lesions (NCCLs). METHOD AND MATERIALS: Thirty-seven patients presenting at least two contralateral teeth with NCCL (one restored and another non-restored) were selected. Non-restored NCCL teeth were classified as a control group, while the contralateral teeth restored within at least 3 months with a Class 5 restoration located near the gingival margin were classified as the test group. The periodontal parameters analyzed were visible plaque, probing depth, bleeding on probing, gingival recession, clinical attachment level, and width of keratinized tissue. Restorative parameters such as finishing/polishing, overhanging margins, and terminal restoration level were also examined. Statistical analysis included the comparison of periodontal and restoration parameters between groups as well as associations between these parameters. Data were statistically analyzed by the Wilcoxon, Fisher's exact, Chi-squared, and Mann-Whitney tests. The significance level was set at 5% (alpha < .05). RESULTS: Statistically significant differences between test and control groups were observed for visible plaque (P = .002), bleeding on probing (P = .041), and width of keratinized tissue (P = .009). Other clinical parameters such as probing depth (P = .812), gingival recession (P = .571), and clinical attachment level (P = .484), as well their associations did not show any statistically significant differences (P > .05). CONCLUSION: Restorative treatment (Class 5) of teeth with NCCL partially influenced the clinical parameters. PMID- 27669721 TI - Is immediate implant placement possible in the maxillary molar area? An anatomical study. AB - The dimensions of maxillary first molars were investigated and measured using cone beam computed tomography (CBCT) to examine the effectiveness of immediate placement of implants in the maxillary molar area. The CBCT images of 68 patients were collected. The dimensions of the maxillary first molar sockets were measured in both sagittal and coronal aspects, as well as the height of the alveolar bone crest (ABC) to the sinus membrane (SM) at optimal implant position. Sinus membrane and maxillary first molar relationships were analyzed sagittally and coronally. Interradicular bone presence and root intrusion into the sinus (IRS) were also noted. No statistically significant relationship was observed between IRS and age or sex. However, IRS was significantly related to sagittal type, as a type 1 sagittal relationship was characterized by greater root intrusion. The socket dimensions of male subjects were statistically significantly greater than those of female subjects, both coronally and sagittally. Changes in the socket dimensions were not significantly related to age in the sagittal plane. However, coronal plane measurements did increase with age. ABC-SM measurements decreased with age, but these changes were not statistically significant. These results showed that the socket dimensions in the maxillary first molar area are adequate for wider implant placement, but an implant longer than 8 mm increased the risk of perforation. All oral surgeons should be familiar with these anatomical variations so they can adopt appropriate additional practices and inform patients about the risks before operating. PMID- 27669723 TI - Transient lingual papillitis. AB - A case of recurrent, clinically innocuous, but painful papules involving the tongue dorsum of a 25-year-old man is presented. The lesions were interpreted to represent a transient lingual papillitis. This a poorly understood, but benign and self-limited condition involving the tongue fungiform papillae, which does not appear to be widely recognized. PMID- 27669722 TI - Clinical retrospective study of self-reported penicillin allergy on dental implant failures and infections. AB - OBJECTIVE: The aim of this retrospective study was to investigate whether self reported allergy to penicillin may contribute to a higher rate of postsurgical infection and implant failure. METHOD AND MATERIALS: This retrospective, non interventional, open cohort study reports on implant survival and infection complications of 5,576 implants placed in private practice by one periodontist, and includes 4,132 implants that were followed for at least 1 year. Logistic regression was applied to examine the relationship between self-reported allergy to penicillin and implant survival, while controlling for potential confounders such as smoking, implant site, bone augmentation, loading protocol, immediate implantation, and bone level at baseline. The cumulative survival rate (CSR) was calculated according to the life table method and the Cox proportional hazard model was fitted to data. RESULTS: Out of 5,106 implants placed in patients taking penicillin it was found that 0.8% failed, while 2.1% failed of the 470 implants placed for patients with self-reported allergy to penicillin (P = .002). Odds of failure for implants placed in penicillin-allergic patients were 3.1 times higher than in non-allergic patients. For immediate implant placement, penicillin-allergic patients had a failure rate 10-times higher than the non allergic cohort. Timing of implant failure occurring within 6 months following implantation was 80% in the penicillin-allergic group versus 54% in the non allergic group. From the 48 implant sites showing postoperative infection: penicillin-allergic patients had an infection rate of 3.4% (n = 16/470) versus 0.6% in the non-allergic group (n = 32/5,106) (P < .05). CONCLUSION: Self reported penicillin allergy was associated with a higher rate of infection, and primarily affected early implant failure. PMID- 27669724 TI - Invasive cervical resorption following orthodontic treatment: Two cases involving the same patient. AB - : Invasive cervical resorption (ICR), a destructive form of external root resorption, is characterized by invasion of the fibrovascular tissue. This phenomenon is very rare and appears in 0.02% of the general population where the leading factors are orthodontics in addition to trauma, restorations, and bleaching. Heavy orthodontic force may increase the incidence to 1%. One of the main concerns regarding ICR is that it is often misdiagnosed with conventional diagnostic tools. In recent decades, a cone beam computed tomography (CBCT) imaging technique has become more common and can lead to a more accurate diagnosis and treatment plan. This case report describes a possible association between orthodontic treatment and ICR of a 14-year-old male, 18 months post orthodontic treatment. ICR in the mandibular right canine was diagnosed and verified by CBCT, and underwent combined endodontic-periodontal treatment. However, after orthodontic forced eruption was performed on this tooth to improve the bone defect, ICR was diagnosed on the mandibular right second premolar. The possible association between orthodontic treatment and ICR is discussed, as ICR was noted following orthodontic treatment on both occasions. This case report stresses the importance of ICR early detection by close attention to periodic radiographic checkups during orthodontic treatment. The use of modern diagnostic tools is highly recommended in suspicious cases. CONCLUSION: A case is described in which the patient underwent two types of orthodontic treatment in the mandible at different time periods and developed ICR in two different teeth. PMID- 27669725 TI - Comparison of self-perceived oral symptoms and periodontal parameters among habitual ?shamma-chewers, gutka-chewers, and non-chewers. AB - OBJECTIVE: There are no studies that have (a) compared self-perceived oral symptoms and clinical and radiographic periodontal parameters (plaque index [PI], bleeding on probing [BoP], clinical attachment loss [CAL], and marginal bone loss [MBL]) among shamma-chewers (SC) and gutka-chewers (GC); and (b) assessed periodontal parameters among SC. The aim of the present study was to compare the self-perceived oral symptoms and periodontal parameters among SC, GC, and controls. METHOD AND MATERIALS: Information regarding demographic characteristics and self-perceived oral symptoms was gathered using a structured questionnaire. Odds ratios were computed for self-perceived oral symptoms and periodontal parameters and compared between the groups. For multiple comparisons, the Bonferroni post-hoc test was used. Level of significance was set at P < .05. RESULTS: Forty-seven SC, 45 GC, and 41 control individuals were included. Group comparisons for pain in teeth, pain on chewing, bleeding gums, and burning sensation in the mouth showed no statistically significant difference among SC and GC. These symptoms were significantly higher in SC (P < .01) and GC (P < .01) than controls. PI, BoP, PD (4-6 mm and > 6 mm), and CAL were significantly higher in SC (P < .05) and GC (P < .05) than controls. There was no statistically significant difference in PI, BoP, PD (4-6 mm and > 6 mm), and CAL among SC and GC. There was no statistically significant influence of daily frequency of smokeless tobacco consumption and duration of placement in the mouth on the severity of periodontal parameters. CONCLUSION: Self-perceived oral symptoms and periodontal parameters were worse among SC and GC than controls, with no statistically significant difference when comparing these findings between SC and GC. PMID- 27669726 TI - Factors associated with postobturation pain following single-visit nonsurgical root canal treatment: ?A systematic review. AB - OBJECTIVE: Reducing the pain after root canal therapy is a key aspect in endodontic practice. The present systematic review aimed to identify the factors that influence postobturation pain (POP) in patients receiving single-visit nonsurgical root canal treatment. DATA SOURCES: A literature search was performed manually and in Pubmed (Medline) database to identify relevant articles. A data extraction form was constructed and data were collected from the identified articles. RESULTS: In total, 24 articles were identified for the systematic review, and factors associated with POP were tabulated. CONCLUSION: Specific preoperative factors (old age, sex, molar teeth, mandibular teeth, presence of preoperative pain, and absence of periapical radiolucency) and procedures (administration of prophylactic drug, bupivicaine anesthetic agent, radiograph or apex locator working length determination methods, instrumentation, irrigating system, laser, cold lateral compaction obturation technique, reducing the occlusion, and postoperative drugs) were associated with POP. PMID- 27669727 TI - Evaluation of root canal transportation, centering ratio, and remaining dentin thickness of TRUShape and ProTaper Next systems in curved root canals using micro computed tomography. AB - OBJECTIVE: To evaluate and compare the volume of removed dentin, transportation, and centering ability of TRUShape (TRS; Dentsply Tulsa Dental Specialties) system with ProTaper Next (PTN; Dentsply Maillefer) by using micro-computed tomography (uCT). METHOD AND MATERIALS: Twenty extracted human mandibular first molars with two separate mesial canals with curvatures of 25 to 35 degrees were divided into two experimental groups (n = 20) according to the rotary nickel-titanium file system used in canal instrumentation as follows: group TRS and group PTN. Canals were scanned before and after instrumentation using uCT to evaluate root canal transportation, centering ratio, and volumetric changes. Data of canal transportation and centering ratio values were analyzed using independent t test. Volume changes data were statistically analyzed using Mann-Whitney test. Statistical significance level was set at P < .05. RESULTS: The PTN group had a significantly lower mean volume of removed dentin (2.09 +/- 0.41 mm3) than the TRS group (2.77 +/- 0.72 mm3) (P < .05). At the coronal level, there was no significant difference in canal transportation (P = .170) and centering ratio (P = .111) between TRS and PTN groups. However, at the apical and middle levels, the PTN group had a significantly lower mean transportation value and higher centering ratio than the TRS group (P < .05). CONCLUSION: Root canal preparation with the PTN system revealed better performance with fewer canal aberrations than the TRS system in curved root canals. PMID- 27669728 TI - Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis. AB - INTRODUCTION: Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI). METHODS: Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ?0.2 mV in anterior, ?0.1 mV in lateral, inferior, right ventricular or high right anterior and ?0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12 lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ?0.1 ug/L. RESULTS: Enrolled were 400 patients (age 62 +/- 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 +/- 5.6 kg/m2. Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ?0.3 mV using TVCM ( n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used. CONCLUSION: Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis. PMID- 27669729 TI - Age-specific prognostication after out-of-hospital cardiac arrest - The ethical dilemma between 'life-sustaining treatment' and 'the right to die' in the elderly. AB - BACKGROUND: While prognostic values on survival after out-of-hospital cardiac arrest have been well investigated, less attention has been paid to their age specific relevance. Therefore, we aimed to identify suitable age-specific early prognostication in elderly patients suffering out-of-hospital cardiac arrest in order to reduce the burden of unnecessary treatment and harm. METHODS: In a prospective population-based observational trial on individuals suffering out-of hospital cardiac arrest, a total of 2223 patients receiving resuscitation attempts by the local emergency medical service in Vienna, Austria, were enrolled. Patients were stratified according to age as follows: young and middle aged individuals (<65 years), young old individuals (65-74 years), old individuals (75-84 years) and very old individuals (>85 years). RESULTS: There was an increasing rate of 30-day mortality (+21.8%, p < 0.001) and unfavourable neurological outcome (+18.8%, p < 0.001) with increasing age among age groups. Established predictive variables lost their prognostic potential with increasing age, even after adjusting for potential confounders. Independently, an initially shockable electrocardiogram proved to be directly associated with survival, with an adjusted hazard ratio (HR) of 2.04 (95% confidence interval (CI) 1.89-2.38, p = 0.003) for >85-year-olds. Frailty was directly associated with mortality (HR 1.22, 95% CI 1.01-1.51, p = 0.049), showing a 30-day survival of 5.6% and a favourable neurological outcome of 1.1% among elderly individuals. CONCLUSION: An initially shockable electrocardiogram proved to be a suitable tool for risk assessment and decision making in order to predict a successful outcome in elderly victims of out-of-hospital cardiac arrest. However, the outcomes of elderly patients seemed to be exceptionally poor in frail individuals and need to be considered in order to reduce unnecessary treatment decisions. PMID- 27669731 TI - A Randomized Controlled Trial Exploring the Effects of Brief Anger Management on Community-Based Offenders in Malta. AB - The aim of this article is to examine the effects of a short-term one-to-one anger management program delivered to community-based offenders in Malta. The program delivered was the Individual Managing Anger Program (I-MAP), a Cognitive behavioural therapy (CBT) and mindfulness-based anger management intervention developed as an EU project. A randomized control trial (RCT)with waitlist controls was carried out to investigate the effects of I-MAP on the reduction in anger dysfunction among offenders serving a community-based sanction. Participants were 24 male offenders aged between 18 and 57. Eligibility for treatment was based on screening for anger dysfunction and success of interventions was determined through psychometric measures. All the statistical analyses carried out showed significant reduction in psychometric scores on anger symptoms. Results of the interventions show clinical significance. These results are discussed in light of recent research. PMID- 27669732 TI - Sex Offending and Situational Motivation: Findings From a Qualitative Analysis of Desistance From Sexual Offending. AB - Sex offending is typically understood from a pathology perspective with the origin of the behavior thought to be within the offending individual. Such a perspective may not be beneficial for those seeking to desist from sexual offending and reintegrate into mainstream society. A thematic analysis of 32 self narratives of men convicted of sexual offences against children suggests that such individuals typically explain their pasts utilizing a script consistent with routine activity theory, emphasizing the role of circumstantial changes in both the onset of and desistance from sexual offending. It is argued that the self framing of serious offending in this way might be understood as a form of "shame management," a protective cognition that enables desistance by shielding individuals from internalizing stigma for past violence. PMID- 27669730 TI - Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes. AB - Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony stimulating factor (G-CSF) preserves beta-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4 24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12 month C-peptide >= baseline), "super responders" (24-month C-peptide >= baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G CSF as a prevention strategy in high-risk subjects. PMID- 27669733 TI - Mechanisms Underlying Acrolein-Mediated Inhibition of Chromatin Assembly. AB - Acrolein is a major component of cigarette smoke and cooking fumes. Previously, we reported that acrolein compromises chromatin assembly; however, underlying mechanisms have not been defined. Here, we report that acrolein reacts with lysine residues, including lysines 5 and 12, sites important for chromatin assembly, on histone H4 in vitro and in vivo Acrolein-modified histones are resistant to acetylation, suggesting that the reduced H4K12 acetylation that occurs following acrolein exposure is probably due to the formation of acrolein histone lysine adducts. Accordingly, the association of H3/H4 with the histone chaperone ASF1 and importin 4 is disrupted and the translocation of green fluorescent protein-tagged H3 is inhibited in cells exposed to acrolein. Interestingly, in vitro plasmid supercoiling assays revealed that treatment of either histones or ASF1 with acrolein has no effect on the formation of plasmid supercoiling, indicating that acrolein-protein adduct formation itself does not directly interfere with nucleosome assembly. Notably, exposure of histones to acrolein prior to histone acetylation leads to the inhibition of remodeling and spacing factor chromatin assembly, which requires acetylated histones for efficient assembly. These results suggest that acrolein compromises chromatin assembly by reacting with histone lysine residues at the sites critical for chromatin assembly and prevents these sites from physiological modifications. PMID- 27669735 TI - Bone Densitometry in Children and Adolescents. AB - Concerns about bone health and potential fragility in children and adolescents have led to a high interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve expected gains in bone size, mass, and strength, leaving them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less clear. This clinical report summarizes current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and risks and costs. The report emphasizes updated consensus statements generated at the 2013 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, whereas others reflect expert opinion, because data are sparse on many topics. The statements from this and other expert panels provide general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. The interpretation of bone densitometry results in children differs from that in older adults. The terms "osteopenia" and "osteoporosis" based on bone densitometry findings alone should not be used in younger patients; instead, bone mineral content or density that falls >2 SDs below expected is labeled "low for age." Pediatric osteoporosis is defined by the Pediatric Position Development Conference by using 1 of the following criteria: >=1 vertebral fractures occurring in the absence of local disease or high-energy trauma (without or with densitometry measurements) or low bone density for age and a significant fracture history (defined as >=2 long bone fractures before 10 years of age or >=3 long bone fractures before 19 years of age). Ongoing research will help define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk. The Pediatric Endocrine Society affirms the educational value of this publication. PMID- 27669734 TI - Regulation of Linear Ubiquitin Chain Assembly Complex by Caspase-Mediated Cleavage of RNF31. AB - Cell death and survival signaling pathways have opposed but fundamental functions for various cellular processes and maintain cell homeostasis through cross talk. Here we report a novel mechanism of interaction between these two pathways through the cleavage of RNF31 by caspases. RNF31, a component of the linear ubiquitin chain assembly complex (LUBAC), regulates cell survival by inducing linear ubiquitination of NF-kappaB signaling components. We found that RNF31 is cleaved under apoptosis conditions through various stimulations. The effector caspases caspase 3 and caspase 6 are responsible for this event, and aspartates 348, 387, and 390 were identified as target sites for this cleavage. Cleavage of RNF31 suppressed its ability to activate NF-kappaB signaling; thus, mutation of cleavage sites inhibited the induction of apoptosis by treatment with tumor necrosis factor alpha (TNF-alpha). Our findings elucidate a novel regulatory loop between cell death and the survival signal and may provide guidance for the development of therapeutic strategies for cancers through the sensitization of tumor cells to death-inducing drugs. PMID- 27669736 TI - Risk of Autism Associated With Hyperbilirubinemia and Phototherapy. AB - OBJECTIVE: Whether neonatal hyperbilirubinemia and/or phototherapy increase the risk of autism spectrum disorder (ASD) is unclear. We sought to quantify the risk of ASD associated with elevated total serum bilirubin (TSB) levels and with phototherapy. METHODS: In a retrospective cohort study of 525 409 infants born at >=35 weeks' gestation in 15 Kaiser Permanente Northern California (KPNC) hospitals, 1995-2011, we obtained all TSB levels and determined which infants received phototherapy. From the KPNC Autism Registry, we identified patients with ASD diagnosed at a KPNC Autism Center, by a clinical specialist, or by a pediatrician. We calculated Cox proportional hazard ratios (HRs) for time to diagnosis of ASD, adjusting for confounding factors. RESULTS: Among infants in the birth cohort, 2% had at least 1 TSB level >=20 mg/dL, and 8% received phototherapy. The rate of ASD was 13 per 1000 births. Crude analyses revealed an association between TSB >=20 and ASD (relative risk: 1.4; 95% confidence interval [CI]: 1.1-1.6), and between phototherapy and ASD (relative risk: 1.7; 95% CI: 1.5 1.8). After adjusting for confounders, TSB >=20 (HR: 1.09; 95% CI: 0.89-1.35) and phototherapy (HR: 1.10; 95% CI: 0.98-1.24) were no longer significantly associated with ASD. Independent risk factors for ASD included maternal and paternal age; maternal and paternal higher education; male sex; birth weight <2500 g or >=4200 g; and later year of birth. CONCLUSIONS: After adjustment for the effects of sociodemographic factors and birth weight, neither hyperbilirubinemia nor phototherapy was an independent risk factor for ASD. PMID- 27669737 TI - Changes in Moderate-to-Vigorous Physical Activity Among Older Adolescents. AB - OBJECTIVES: Examined patterns and determinants of objectively measured moderate to-vigorous physical activity (MVPA) over 4 years in US emerging adults. METHODS: Waves 1 through 4 (W1 [10th grade] to W4 data of a national cohort starting in 2010 (N = 561; 16.19 +/- 0.51 years) were used. MVPA was assessed annually from accelerometers; BMI calculated from measured height/weight; and surveys ascertained self-reported physical activity (PA) planning, peer PA , family support, W1 sociodemographics, W4 school status, W4 residence, and W4 employment. Latent growth modeling estimated trajectories in log-transformed duration (minutes/day) of MVPA and associations with covariates. RESULTS: Less than 9% of participants met the recommended 60+ minutes/day MVPA across W1 through W4. W1 MVPA was greater in males versus females (B = 0.46, P < .001) and Hispanic versus White (B = 0.34, P < .001) participants. Increased BMI change (W1 to W4 slope) was associated with decreased MVPA. MVPA was positively associated with PA planning (W1-W3: B = 0.10, B = 0.06, B = 0.08, Ps < .05), but not with peer PA or family support. Participants attending 4-year college versus not-attending school (B = 0.52, P < .001), and college students living on campus versus at home (B = 0.37, P < .001) were more likely to engage in MVPA at W4. Weekend MVPA remained relatively constant from W1 through W4. CONCLUSIONS: High-school students engaged in little MVPA and maintained this low level through the transition to adulthood. Emerging adults' MVPA engagement may vary according to social contexts. Those with high BMI may benefit most from interventions to promote MVPA. PMID- 27669740 TI - Daptomycin Leakage Is Selective. AB - Daptomycin is a lipopeptide antibiotic approved for use against Gram-positive organisms, including highly resistant species. A number of studies have suggested that daptomycin kills bacteria by membrane permeabilization and depolarization. Recently a model membrane system consisting of 1,2-dimyristoyl-sn-glycero-3 phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) in a 1:1 ratio and the ionophore CCCP was proposed as a simple model to investigate the mode of action of daptomycin and resistance mechanisms at a molecular level. This study investigates how this model depends on the composition of the membrane and the role of CCCP. Results obtained from a fluorescence assay using pyranine show that daptomycin causes leakage in liposomes of limited stability and that CCCP promotes this leakage. A different model membrane system used here, which relies on ion selective dyes such as 4,4'-[1,4,10,13-tetraoxa-7,16 diazacyclooctadecane-7,16-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetrakis[(acetyloxy)methyl] ester (PBFI), and 4,4'-[1,4,10-trioxa-7,13 diazacyclopentadecane-7,13-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetraammonium salt (SBFI), is a more robust alternative. Findings based on this newer model suggest that daptomycin is selective for potassium. PMID- 27669738 TI - Associations of P16INK4a promoter hypermethylation with squamous intra-epithelial lesion, cervical cancer and their clinicopathological features: a meta-analysis. AB - To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis. PMID- 27669739 TI - The human nucleophosmin 1 mutation A inhibits myeloid differentiation of leukemia cells by modulating miR-10b. AB - Mutations in the nucleophosmin 1 (NPM1) gene are the most frequent genetic alteration in acute myeloid leukemia (AML). Here, we showed that enforced expression of NPM1 mutation type A (NPM1-mA) inhibits myeloid differentiation of leukemia cells, whereas knockdown of NPM1-mA has the opposite effect. Our analyses of normal karyotype AML samples from The Cancer Genome Atlas (TCGA) dataset revealed that miR-10b is commonly overexpressed in NPM1-mutated AMLs. We also found high expression of miR-10b in primary NPM1-mutated AML blasts and NPM1 mA positive OCI-AML3 cells. In addition, NPM1-mA knockdown enhanced myeloid differentiation, while induced expression of miR-10b reversed this effect. Finally, we showed that KLF4 is downregulated in NPM1-mutated AMLs. These results demonstrated that miR-10b exerts its effects by repressing the translation of KLF4 and that NPM1-mA inhibits myeloid differentiation through the miR-10b/KLF4 axis. This sheds new light on the effect of NPM1 mutations' on leukemogenesis. PMID- 27669741 TI - The factor structure of the 12-item general health questionnaire (GHQ-12) in young Chinese civil servants. AB - BACKGROUND: The 12-item General Health Questionnaire (GHQ-12) is a commonly used screening instrument for measuring mental disorders. However, few studies have measured the mental health of Chinese professionals or explored the factor structure of the GHQ-12 through investigations of young Chinese civil servants. METHOD: This study analyses the factor structure of the GHQ-12 on young Chinese civil servants. Respondents include 1051 participants from six cities in eastern China. Exploratory Factor Analysis (EFA) is used to identify the potential factor structure of the GHQ-12. Confirmatory Factor Analysis (CFA) models of previous studies are referred to for model fitting. RESULTS: The results indicate the GHQ 12 has very good reliability and validity. All ten CFA models are well fitted with the actual data. CONCLUSION: All the ten models are feasible and fit the data equally well. The Chinese version of the GHQ-12 is suitable for professional groups and can serve as a screening tool to detect anxiety and psychiatric disorders. PMID- 27669742 TI - ITRAQ-Based Proteomic Analysis of the Metabolic Mechanisms Behind Lipid Accumulation and Degradation during Peanut Seed Development and Postgermination. AB - Peanut seeds have a high oil content making them an important oil crop. During development and germination, seeds undergo complex dynamic and physiological changes. Changes in lipid metabolism and underlying mechanisms during seed development have been studied extensively by DNA and RNA sequencing; however, there are few studies on dynamic changes of proteomics during peanut seed development and germination. In this study, proteomic analyses were carried out 20, 40, 60, and 80 days after pollination and 5, 10, 20, and 30 days after germination using isobaric tags for relative and absolute quantitation (iTRAQ) technology to determine the protein profiles of lipid dynamics during peanut seed development and postgermination. A total of 5712 of 8505 proteins were identified, quantified, and divided into 23 functional groups, the largest of which was metabolism-related. Further analyses of the proteins and their pathways revealed initiation of fatty acid accumulation at early stages after flowering, while lipid degradation occurred largely through the lipoxygenase-dependent pathway. Protein expression patterns related to lipid accumulation and degradation were also verified at transcript levels using quantitative real-time polymerase chain reaction. The proteome profiles determined here will significantly enrich our understanding of the process of lipid accumulation and degradation and the dynamic changes in metabolic networks during peanut development. PMID- 27669743 TI - Couplings Across the Vibrational Spectrum Caused by Strong Hydrogen Bonds: A Continuum 2D IR Study of the 7-Azaindole-Acetic Acid Heterodimer. AB - Strongly hydrogen-bonded motifs provide structural stability and can act as proton transfer relays to drive chemical processes in biological and chemical systems. However, structures with medium and strong hydrogen bonds are difficult to study due to their characteristically broad vibrational bands and large anharmonicity. This is further complicated by strong interactions between the high-frequency hydrogen-bonded vibrational modes, fingerprint modes, and low frequency intradimer modes that modulate the hydrogen-bonding. Understanding these structures and their associated dynamics requires studying much of the vibrational spectrum. Here, mid-IR continuum spectroscopy of the cyclic 7 azaindole-acetic acid (7AI-AcOH) heterodimer reveals the vibrational relaxation dynamics and couplings of this complex hydrogen-bonded system. Within this dimer, the NH bond of 7AI exhibits a band at 3250 cm-1 caused by a medium strength hydrogen bond, while the strongly hydrogen-bonded OH modes of acetic acid exhibit a broad double-peaked vibrational feature spanning 1750 to 2750 cm-1. Transient IR and 2D IR experiments were performed using three excitation frequencies, centered on the high-frequency OH and NH modes, and probed with a mid-IR continuum to measure the spectral response from 1000 to 3500 cm-1. While the NH stretch is observed to relax in 300 fs, the strongly hydrogen-bonded OH modes relax within the time resolution of the experiment (sub-100 fs). The difference in the strength of the hydrogen bonds is also reflected in the coupling pattern in the fingerprint region observed with 2D IR spectroscopy. Here the NH is strongly coupled to fingerprint modes involving the 7AI monomer, while the OH vibrations are strongly coupled to vibrational modes across the entire dimer. Together, the results show strong coupling and rapid energy transfer across the hydrogen-bonded interface and through the structure of the 7-azaindole-acetic acid heterodimer, highlighting the need to study the full vibrational spectrum for strongly hydrogen-bonded systems. PMID- 27669744 TI - De novo transcriptomic analysis of Chlorella sorokiniana reveals differential genes expression in photosynthetic carbon fixation and lipid production. AB - BACKGROUND: Microalgae, which can absorb carbon dioxide and then transform it into lipid, are promising candidates to produce renewable energy, especially biodiesel. The paucity of genomic information, however, limits the development of genome-based genetic modification to improve lipid production in many microalgae. Here, we describe the de novo sequencing, transcriptome assembly, annotation and differential expression analysis for Chlorella sorokiniana cultivated in different conditions to reveal the change of genes expression associated with lipid accumulation and photosynthetic carbon fixation. RESULTS: Six cultivation conditions were selected to cultivate C. sorokiniana. Lipid content of C. sorokiniana under nitrogen-limited condition was 2.96 times than that under nitrogen-replete condition. When cultivated in light with nitrogen-limited supply, C. sorokiniana can use carbon dioxide to accumulate lipid. Then, transcriptome of C. sorokiniana was sequenced using Illumina paired-end sequencing technology, and 244,291,069 raw reads with length of 100 bp were produced. After preprocessed, these reads were de novo assembled into 63,811 contigs among which 23,528 contigs were found homologous sequences in public databases through Blastx. Gene expression abundance under six conditions were quantified by calculating FPKM value. Ultimately, we found 385 genes at least 2 fold up-regulated while 71 genes at least 2-fold down-regulated in nitrogen limited condition. Also, 204 genes were at least 2-fold up-regulated in light while 638 genes at least 2-fold down-regulated. Finally, 16 genes were selected to conduct RT-qPCR and 15 genes showed the similar results as those identified by transcriptomic analysis in term of differential expression. CONCLUSIONS: De novo transcriptomic analyses have generated enormous information over C. sorokiniana, revealing a broad overview of genomic information related to lipid accumulation and photosynthetic carbon fixation. The genes with expression change under different conditions are highly likely the potential targets for genetic modification to improve lipid production and CO2 fixation efficiency in oleaginous microalgae. PMID- 27669745 TI - Ethnic inequalities in cancer incidence and mortality: census-linked cohort studies with 87 million years of person-time follow-up. AB - BACKGROUND: Cancer makes up a large and increasing proportion of excess mortality for indigenous, marginalised and socioeconomically deprived populations, and much of this inequality is preventable. This study aimed to determine which cancers give rise to changing ethnic inequalities over time. METHODS: New Zealand census data from 1981, 1986, 1991, 1996, 2001, and 2006, were all probabilistically linked to three to five subsequent years of mortality (68 million person-years) and cancer registrations (87 million person years) and weighted for linkage bias. Age-standardised rate differences (SRDs) for Maori (indigenous) and Pacific peoples, each compared to European/Other, were decomposed by cancer type. RESULTS: The absolute size and percentage of the cancer contribution to excess mortality increased from 1981-86 to 2006-11 in Maori males (SRD 72.5 to 102.0 per 100,000) and females (SRD 72.2 to 109.4), and Pacific females (SRD -9.8 to 42.2) each compared to European/Other. Specifically, excess mortality (SRDs) increased for breast cancer in Maori females (linear trend p < 0.01) and prostate (p < 0.01) and colorectal cancers (p < 0.01) in Maori males. The incidence gap (SRDs) increased for breast (Maori and Pacific females p < 0.01), endometrial (Pacific females p < 0.01) and liver cancers (Maori males p = 0.04), and for cervical cancer it decreased (Maori females p = 0.03). The colorectal cancer incidence gap which formerly favoured Maori, decreased for Maori males and females (p < 0.01). The greatest contributors to absolute inequalities (SRDs) in mortality in 2006-11 were lung cancer (Maori males 50 %, Maori females 44 %, Pacific males 81 %), breast cancer (Maori females 18 %, Pacific females 23 %) and stomach cancers (Maori males 9 %, Pacific males 16 %, Pacific females 20 %). The top contributors to the ethnic gap in cancer incidence were lung, breast, stomach, endometrial and liver cancer. CONCLUSIONS: A transition is occurring in what diseases contribute to inequalities. The increasing excess incidence and mortality rates in several obesity- and health care access-related cancers provide a sentinel warning of the emerging drivers of ethnic inequalities. Action to further address inequalities in cancer burden needs to be multi-pronged with attention to enhanced control of tobacco, obesity, and carcinogenic infectious agents, and focus on addressing access to effective screening and quality health care. PMID- 27669746 TI - The effectiveness of extracorporeal membrane oxygenation in a patient with post myocardial infarct ventricular septal defect. AB - BACKGROUND: Post infarction ventricular septal defect (VSD) is an uncommon but life threatening complication of acute myocardial infarction. CASE PRESENTATION: A 62-year-old woman was admitted with acute myocardial infarction (AMI). However, the day after angioplasty and stenting, Transthoracic echocardiography (TTE) showed post infarction VSD. We decided to insert an extracorporeal membrane oxygenation (ECMO) device for stabilization purposes before surgical repair. After 4 days from the implantation, we performed surgical repair successfully. CONCLUSIONS: When optimal medical treatment fails to stabilize a patient in cardiogenic shock, peripheral ECMO could be used as a bridge to definitive surgical therapy. PMID- 27669748 TI - Erratum to: Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue. PMID- 27669747 TI - Assessment of three fasting plasma glucose targets for insulin glargine-based therapy in people with type 2 diabetes mellitus in China: study protocol for a randomized controlled trial. AB - BACKGROUND: A large proportion of patients with T2DM in China do not meet accepted HbA1c targets despite the availability of guidelines that describe a treatment pathway for achieving glycemic control. The aim of this study is to identify the fasting plasma glucose (FPG) target that will provide the highest control rate of HbA1c <7 % in Chinese patients with T2DM treated with an insulin glargine-based regimen as an adjunct to an established OAD regimen. This information will support improvements in diabetes care management in China. METHODS: Approximately 934 men and women aged >=18 to <=65 years with poorly controlled T2DM will be enrolled and randomized to one of three FPG target groups; <=5.6 mmol/L, <=6.1 mmol/L, or <=7.0 mmol/L. They will be initiated on daily insulin glargine (Lantus(r)) in addition to their usual OAD regimen for 24 weeks. Patients will self-monitor fasting blood glucose (SM-FBG), and the study physician will titrate the basal insulin dose according to the SM-FBG results. In addition, HbA1c and safety will be recorded. We plan to statistically derive the optimal FPG target for an HbA1c of <7 %. DISCUSSION: In China, treatment strategies that would achieve an optimum balance between glycemic control (as per HbA1c) and hypoglycemia are imperative to ensure improvements in the management of T2DM. Furthermore, elucidating the contribution of FPG to HbA1c in Chinese patients with T2DM and identifying a predictable relationship between FPG and HbA1c would be a valuable tool for patient self-management of diabetes. TRIAL REGISTRATION: NCT02545842 . Registered on 8 September 2015. PMID- 27669754 TI - Evaluation of metal contamination and phytoremediation potential of aquatic macrophytes of East Kolkata Wetlands, India. AB - OBJECTIVES: The present study analyzes metal contamination in sediment of the East Kolkata Wetlands, a Ramsar site, which is receiving a huge amount of domestic and industrial wastewater from surrounding areas. The subsequent uptake and accumulation of metals in different macrophytes are also examined in regard to their phytoremediation potential. METHODS: Metals like cadmium (Cd), copper (Cu), manganese (Mn), and lead (Pb) were estimated in sediment, water and different parts of the macrophytes Colocasia esculenta and Scirpus articulatus. RESULTS: The concentration of metals in sediment were, from highest to lowest, Mn (205.0+/-65.5 mg/kg)>Cu (29.9+/-10.2 mg/kg)>Pb (22.7+/-10.3 mg/kg)>Cd (3.7+/-2.2 mg/kg). The phytoaccumulation tendency of these metals showed similar trends in both native aquatic macrophyte species. The rate of accumulation of metals in roots was higher than in shoots. There were strong positive correlations (p<0.001) between soil organic carbon (OC) percentage and Mn (r =0.771), and sediment OC percentage and Pb (r=0.832). Cation exchange capacity (CEC) also showed a positive correlation (p<0.001) with Cu (r=0.721), Mn (r=0.713), and Pb (r=0.788), while correlations between sediment OC percentage and Cu (r=0.628), sediment OC percentage and Cd (r=0.559), and CEC and Cd (r=0.625) were significant at the p<0.05 level. CONCLUSIONS: Bioaccumulation factor and translocation factors of these two plants revealed that S. articulatus was comparatively more efficient for phytoremediation, whereas phytostabilization potential was higher in C. esculenta. PMID- 27669757 TI - An Update from Flatland. PMID- 27669756 TI - Reproducibility with repeat CT in radiomics study for rectal cancer. AB - PURPOSE: To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. RESULTS: Volume normalized features are much more reproducible than unnormalized features. The average value of all slices is the most reproducible feature type in rectal cancer. Different filters have little effect for the reproducibility of radiomics features. For the average type features, 496 out of 775 features showed high reproducibility (ICC >= 0.8), 225 out of 775 features showed medium reproducibility (0.8 > ICC >= 0.5) and 54 out of 775 features showed low reproducibility (ICC < 0.5). METHODS: 40 rectal cancer patients with stage II were enrolled in this study, each of whom underwent two CT scans within average 8.7 days. 775 radiomics features were defined in this study. For each features, five different values (value from the largest slice, maximum value, minimum value, average value of all slices and value from superposed intermediate matrix) were extracted. Meanwhile a LOG filter with different parameters was applied to these images to find stable filter value. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) of two CT scans were calculated to assess the reproducibility, based on original features and volume normalized features. CONCLUSIONS: Features are recommended to be normalized to volume in radiomics analysis. The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction.to modulate two anticancer compounds in well-defined sets of GBM patients. PMID- 27669755 TI - Fibroblast growth factor receptor (FGFR) alterations in squamous differentiated bladder cancer: a putative therapeutic target for a small subgroup. AB - Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis). Only single cases displayed enhanced protein expression, most frequently FGFR3 overexpression (9.4% (6/64)). FISH showed no amplifications of FGFR1, 2 or 3. Break apart events were only slightly above the cut off in 12.1% (8/66) of cases and no FGFR3-TACC3 rearrangements could be proven by qPCR. FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 protein overexpression (p < 0.001), and unfavourable clinical outcome (p = 0.001). Our findings are consistent with the results of the TCGA data set for the "squamous like" subtype of bladder cancer (n = 85), which revealed reduced overall expression of FGFR1 and FGFR2 in tumors compared to normal tissue, while expression of FGFR3 remained high. In the TCGA "squamous-like" subtype FGFR3 mutations were found in 4.9% and correlated with high FGFR3 RNA expression. Mutations of FGFR1 and FGFR2 were less frequent (2.4% and 1.2%). Hence, our comprehensive study provides novel insights into a subgroup of squamous differentiated bladder tumors that hold clues for novel therapeutic regimens and may benefit from FGFR3-targeted therapies. PMID- 27669759 TI - Spent mushroom substrate biochar as a potential amendment in pig manure and rice straw composting processes. AB - Spent mushroom substrate (SMS) is a bulky waste byproduct of commercial mushroom production, which can cause serious environmental problems and, therefore, poses a significant barrier to future expansion of the mushroom industry. In the present study, we explored the use of SMS as a biochar to improve the quality of bio-fertilizer. Specifically, we performed a series of experiments using composting reactors to investigate the effects of SMS biochar on the physio chemical properties of bio-fertilizer. Biochar was derived from dry SMS pyrolysed at 500 degrees C and mixed with pig manure and rice straw. Results from this study demonstrate that the addition of biochar significantly reduced electrical conductivity and loss of organic matter in compost material. Nutrient analysis revealed that the SMS-derived biochar is rich in fertilizer nutrients such as P, K, Na, and N. All of these findings suggest that SMS biochar could be an excellent medium for compost. PMID- 27669760 TI - Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress. AB - O-Linked N-acetyl-beta-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC MS/MS, 990 proteins were identified and quantified. Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O GlcNAcylation status of 24 proteins. Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival. PMID- 27669761 TI - Early effects of fluoro-edenite: correlation between IL-18 serum levels and pleural and parenchymal abnormalities. AB - Fluoro-edenite (FE) is a natural mineral asbestos-like fibrous species first isolated in Biancavilla, Sicily. In order to clarify potential involvement of IL 18 in the pathogenesis of FE-induced chest abnormalities, we analyzed IL-18 serum levels in FE-exposed workers (FEEW) and correlated them with pleural and parenchymal abnormalities. A total of 21 FEEWs, residing in Biancavilla for >30 years, with a working seniority of 17 +/- 6.1 years were examined. High resolution computed tomography scans revealed low grade of fibrosis in 8 (38%) FEEWs, and pleural plaques (PPs) in 13 (62%) FEEWs. The mean IL-18 level was 203.13 +/- 90.43 pg/ml. Pearson correlation showed a significant association (p < 0.0001) between IL-18 and PPs and parenchymal abnormality scores. Data suggest a potential role of IL-18 in the pathogenesis of these diseases. PMID- 27669763 TI - Editorial. AB - Last week hundreds of GPs and nurses gathered to discuss the brave new world of fundholding. Quite an achievement, given the historical demarcation lines between both professions. The doctor-nurse relationship of the handmaiden nurse and paternalistic medic moved on some decads ago. But the relationship that replaced it was an uneasy marriage of two groups who tolerated one another's existence. PMID- 27669765 TI - Bottomley moves on nurse prescribing. AB - Nurses at eight pilot sites will be able to prescribe a range of products this autumn, health secretary Virginia Bottomley told the first joint conference of the Royal College of Nursing and the National Association of Fundholding Practices last week. PMID- 27669762 TI - Pharmacological treatment of borderline personality disorder: a retrospective observational study at inpatient unit in Italy. AB - OBJECTIVE: Borderline personality disorder (BPD) is a high prevalence personality disorder. Pharmacotherapy is commonly used, however, a minority of studies investigated patterns of prescription for BPD, particularly in inpatients unit. We aimed to describe the clinical features and the prescribing practice for BPD patients, and to investigate the possible advantages of a single class of medications or of combined drug treatments in terms of length of stay in hospital. METHODS: This is a retrospective observational study evaluating 109 BPD inpatients from June 2011 to June 2013. RESULTS: There was evidence of an extensive use of drugs: benzodiazepines/hypnotics (85.2%), antipsychotics (78.7%), mood stabilizers (70.4%) and antidepressants (31.5%). Polypharmacy was common (83.5%). A longer length of stay in hospital was associated with the prescription of antipsychotic and/or antidepressant medication, while a shorter hospitalization was associated with the use of a mood stabilizer. CONCLUSIONS: The rates of prescription of different classes of drugs reported in our sample and in similar 'naturalistic' studies highlight a heterogeneous pattern of prescriptions for BPD. Mood stabilizers showed a more favourable profile in terms in length of stay in hospital than antipsychotic and/or antidepressant. Our results reiterate the discrepancy between international recommendations and everyday clinical practice. PMID- 27669766 TI - RCN backs sex lesson nurse. AB - A school nurse at the centre of a row over sex education classes has been backed by the RCN, the school where she was teaching and the trust she works for, despite attacks by politicians. PMID- 27669767 TI - ? AB - There was a huge surprise awaiting Royal College of Midwives General Secretary Ruth Ashton at her retirement party last week. BBC social services correspondent Niall Dickson was on hand with the big red book' to say 'Ruth Ashton, this is your professional life'. Friends, family and colleagues organised the event in which key figures, including her sister Alison and health secretary Virginia Bottomley, paid tribute to Ms Ashton, retiring after 15 years in the top post. She is pictured handing on a relay baton to her successor, Julia Allison, right, after the event at London's Cafe Royal. PMID- 27669768 TI - Nurse tutors angry at loss of autonomy. AB - Nurse tutors are furious that students dismissed from courses are being reinstated on appeal by university bosses with little knowlege of nursing, a United Kingdom Central Council conference in Cardiff was . told last week. PMID- 27669769 TI - ? AB - Four-year-old Belma Salaka who was rescued from Sarajevo on the first children's mercy flight last year has been transferred to the bruin injury rehabilitation unit at Tadworth Court Trust in Surrey. Belma was first treated at Great Ormond Street in August, where she was diagnosed as having a rare form of brain damage possibly caused by an infection brought on by war conditions. The rehabilitation team are working to help Belma do things for herself. Current!)', she Is unable to speak, eat or move independently. She is pictured above with her mother Ziba and sister Samira, who have spent most of their time in hospital with her. PMID- 27669770 TI - Unions win compensation cuts review. AB - Nursing unions have cleared the first hurdle in a bid to halt the government's plan to cut criminal injury compensation. PMID- 27669771 TI - Police may reopen Rampton probe after inquest verdict. AB - Police may reopen investigations into the death of Rampton patient Bryan Marsh after the inquest jury returned an open verdict last week. PMID- 27669774 TI - Croatian hospitals under fire. AB - Researchers fear that humanitarian rules of war have been disregarded with the blatant targeting of hospitals in Croatia during the conflict in the former Yugoslavia. PMID- 27669775 TI - Students facing massive rent rises. AB - New student nurses at Leicester Royal Infirmary are facing a giant 250 per cent rent rise. PMID- 27669776 TI - RCM to fight water birth case. AB - The Royal College of Midwives has launched a legal challenge against a trust's decision to discipline two midwives for taking part in a water birth. It is calling for a Rill judicial review of the case, claiming that the trust's actions were not 'fair or equitable'. PMID- 27669778 TI - Leading the way. AB - The public health function of general practices should underpin everything community nurses and GPs do, said Graham Winyard, medical director at the Department of Health. He said the whole primary health care team must make sure data collected at practice level is sufficiently accurate to plan for the whole community. PMID- 27669777 TI - Nurses need to become GPs' partners. AB - Practice nurses must become full partners in GP practices if clients are to receive highly skilled and appropriate services, the President of the RCN claimed last week. PMID- 27669779 TI - Oncology in community trial works. AB - Shifting oncology nursing services to the community can have a marked impact on the lifestyles of cancer patients, the conference heard. PMID- 27669781 TI - Rehab training vital for nurses. AB - Intensive nurse-led rehabilitation can dramatically cut hospital stays, releasing acute hospital beds and saving money, a clinical nurse manager told the conference. PMID- 27669780 TI - Fundholding so successful 'it could rival private sector'. AB - The benefits to patients from fundholding will increase further as more practices join the scheme, a leading health economist told a conference press briefing. PMID- 27669782 TI - Improving primary health care through partnership. PMID- 27669783 TI - Promotion needs input from elderly. AB - Older people must be allowed to set their own health promotion agenda rather than having national targets thrust upon them, Stuart Darby, head of Islington Health Authority's community nursing development team told the conference. PMID- 27669784 TI - Purchasing decisions should reflect nursing quality. AB - GP fundholders should base hospital purchasing decisions on the quality of nursing care on offer rather than on the length of the hospital's waiting list, Royal College of Nursing General Secretary Christine Hancock told the conference. PMID- 27669786 TI - PCNs left out of the reckoning. AB - Nursing staff shortages are preventing sick children from getting care at home, a conference session heard. PMID- 27669785 TI - ? AB - Practice nurses must beware of pricing themselves out of work, the conference heard. Stephen Henry, Executive Chair of the National Association of Fundholding Practices, claimed the average cost to a practice of a nurse-patient consultation was up to ten times higher than when patients see a GP. PMID- 27669787 TI - Psychiatric nursing courses on the increase. AB - Recruitment to community psychiatric nursing courses has jumped by 18 per cent in the past year - the first time in five years there has been an increase. PMID- 27669790 TI - ? AB - Water pollution poses a massive threat to the health of millions of people unless steps are taken to provide many of the world's fastest growing cities with dean supplies, the government-sponsored charity Water Aid has warned. PMID- 27669788 TI - Nursing home care to come under review in Scotland. AB - The Government is considering amendments to the 1938 Nursing Homes Registration Act due to controversy over the quality of care provided by homes, it emerged last week. PMID- 27669791 TI - Death from asthma higher in children from poorer homes. AB - A major national survey of asthma in children has found 'worryingly high' morbidity levels and produced calls for better management of the condition. PMID- 27669792 TI - BMT units still in need of intensive nursing care. AB - The workloads of nurses working in bone marrow transplant units will not be cut by the quicker method of Peripheral Blood Stem Cell Transplantation (PBSCT) for patients with myeloma, a nursing-led study has revealed. PMID- 27669793 TI - Endometriosis Awareness Week. AB - At least 1.5 million women in the UK are affected by endometriosis, The Endometriosis Society claimed last week. The charity, bunching International Endometriosis Awareness Week, said the lives of women affected were being mined by the failure to diagnose the condition and by unnecessary hysterectomies carried out in attempted 'cures'. Pictured is an ovarian cyst caused by the condition. PMID- 27669794 TI - Elderly people urged not to bath when home alone. AB - Elderly people should only have a batch when someone else is in the house and should never lock the door, researchers have urged. The calls follow a survey which found one in seven older people have been trapped in the bath at least once. PMID- 27669796 TI - Fundamental decisions. AB - Though Cecilia Gill is looking forward to getting back to work, she is reluctant to talk about why she has been on sick leave since January. She prefers instead to concentrate on the recent inquest into the death of one of her patients. PMID- 27669795 TI - Two cheers for the changes. AB - The Government's 'care in the community' policy is now a year old. There were many supporters who saw in it official confirmation that large, dehumanising, health and social care institution were finally coming to an end. But others thought that it was mainly a device to allow the Department of Health to shuffle off responsibility for an increasingly expensive area of care. PMID- 27669797 TI - The shape of things to come. AB - The NHS reforms initiated by this government have brought about changes on a scale the service has not experienced since its inception. The mechanisms of the market place have been introduced into this massive national organisation, the biggest employer in Europe. Many commentators remain apprehensive about what can be expected when harsh economic realities replace intangible concepts such as 'public service' as the system's driving force. Will patient care fall by the wayside? Will staff morale be affected? PMID- 27669798 TI - Infection control. AB - This series of ten articles by Dinah Gould looks at infection control in the context of the nursing process, using the activities of daily living model as a framework. The aim of the articles is to emphasise the importance of infection control to clinical nursing practice. The information is not intended to be exhaustive nor to replicate that found in the many textbooks concerned with this subject. It is also important to remember that no model is perfect. Much more is known about the relevant aspects of infection control for some activities of living than for others, so in some cases a category may contain little or even no information. Nevertheless, the articles will help clinical nurses and students to identify the most sensible infection control activities. PMID- 27669799 TI - Footage handled with an eye to sensitivity. AB - As the person responsible for Nursing Update, I write in reply to the correspondent who was concerned at seeing the child about to perform intermittent urinary catheterisation, on the Nursing Update learning unit 'Asking Simple Questions: Promoting Continence' (Video could have nasty consequences, Letters, March 16). PMID- 27669800 TI - Men 'not all bad' - shock claim. AB - I am writing in response to correspondence regarding Mark Crump's letter (Fed up with feminism - withered by women, Letters, February 23). PMID- 27669801 TI - Patient paperwork peeves Penpusher. AB - I am writing as a very disillusioned, concerned, second year Project 2000 student. Please tell me, are wc meant to be nursing paper or patients? PMID- 27669803 TI - Information exchange. AB - I am a third-year Project 2000 nurse searching for information regarding the nursing assessment and management of patients with communication difficulties following a CVA and would be very grateful for any help. PMID- 27669802 TI - Let me through! I'm a helicopter. AB - I enjoyed Pat Goodwin's article about the helicopter emergency medical services in London (Flying to the rescue, Features, March 16). But in a spirit of inquiry and not criticism, would she tell me why, in the case she described of a man who had fallen down basement steps where 'a paramedic team was present', the HEMS team had to clear an airway, intubate and set up an infusion. Surely the paramedic team should have already done all that as a bare minimum? PMID- 27669804 TI - Martha E Rogers. AB - Martha Rogers, a nurse leader and theorist whose significant contribution to the development of nursing theory', practice, education and research cannot be surpassed, died on March 12 at the age of 79. PMID- 27669805 TI - Why is nurses' drinking deemed to he acceptable but not that of patients? Antony Sheehan and Jim Murphy challenge the stereotype. AB - Cutting Edge's recent programme Nurses on Channel 4 was a fine attempt to focus on the plight of nurses at a large teaching hospital in Glasgow. PMID- 27669806 TI - Susie togs on and fights with bytes. AB - Hi there, Health Care Workers! Remember I told you we were about to be computerised? On a whim of the head of the directorate who thought it would make the Unit look more modern? PMID- 27669808 TI - Social Skills for Nursing Practice P French Social Skills for Nursing Practice Chapman & Hall 300pp L13.99 0-412-47840-4 [Formula: see text]. AB - I found Social Skills for Nursing Practice, 2nd edition a frustrating book to review. It has some good material encouraging reflective practice and self direction, but it is presented in a format more in tune with an instructional learning-by-numbers approach. PMID- 27669807 TI - What Katie did next. AB - It was a little over a year ago that I first wrote about my quest for employment as a D Grade Staff Nurse; and it was three months later when I wrote of my success in obtaining a post on an infectious diseases unit. PMID- 27669809 TI - The voluntary agencies directory 1993/94 J Sallon The voluntary agencies directory 1993/94 NCVO 270pp L12.95 0-7199-1339-X. AB - Millions of pounds' worth of valuable resources are available from countless voluntary organisations. At a time of Draconian cuts in public spending, there is a growing need to tap into charities and similar agencies. PMID- 27669810 TI - Elder Abuse G Bennet Kingston P Elder Abuse Chapman & Hall l62pp L14.95 0-412 45310-X. AB - The impact of Elder Abuse: Concepts, Theories and Interventions is in the speed with which it builds up a picture of abuse and inadequate care in all sections of society. There is an extensive review of literature concerning all aspects of the subject of abuse. PMID- 27669812 TI - Listings. PMID- 27669811 TI - Personal power. AB - Aims and intended learning outcomes The aim of this article is to encourage nurses to become aware of their personal power, harness it and use it to enable them to develop personally and professionally. After reading this article the nurse should have an understanding of: ? Definitions and theories of 'power', personal power' and 'powerlessness ? Some of the barriers which stand between people and their personal power: fear, anger, gender issues and lack of values clarification ? Actions which can be taken to begin to dismantle these barriers ? Specific means of enhancing personal power on a personal and professional level. The article relates to UKCC PREP category: Patient, clietit and colleague support. PMID- 27669813 TI - Transitioning from hospitals to the community: perspectives of rehabilitation patients with neurological disorders and their service providers. AB - PURPOSE: To identify the contextual factors that influence community participation in rehabilitation outpatients from the perspectives of patients and their service providers. METHOD: Five focus groups with rehabilitation outpatients (n = 22) and three focus groups with occupational and physical therapists (n = 17) were conducted. Two independent coders thematically analyzed the transcribed data. RESULTS: Patients and their providers identified three common personal factors (personal interests, personal values, and finances) and four major categories of environmental factors (products and technology; support and relationships; attitudes; and services, systems, and policies) that have great influence on patients' participation in the community. Additionally, some patients perceived the impacts of fear of falling and climate on their participation, whereas some service providers reported that age, adaptability, and successful experiences could determine the patients' participation in the community. CONCLUSIONS: This study synthesized and contrasted perspectives from both rehabilitation outpatients and their service providers to identify the contextual factors that enable or restrict patients from participating in the community. Both patients and service providers identified numerous personal and environmental factors associated with participation, thus highlighting areas that can be addressed in rehabilitation outpatient programs and considered in policy development. Implications for Rehabilitation Community participation is an outcome of dynamic interactions among multiple factors and is highly environmentally and culturally sensitive. Both personal and environmental factors have substantial impacts on rehabilitation patients' participation outcomes. Rehabilitation practitioners and policy-makers need to incorporate perspectives from both patients and providers when developing interventions targeting to improve patients' community participation. PMID- 27669814 TI - A comparison of the use of cone-beam computed tomography and panoramic radiography in the assessment of pre-eruptive intracoronal resorption. AB - OBJECTIVE: This study aimed to investigate the prevalence of pre-eruptive intracoronal resorption (PIR) using cone beam computed tomography (CBCT) and panoramic radiography and to compare the findings of these imaging techniques. METHODS: This retrospective study consisted of 733 patients who had at least one unerupted tooth and had undergoneimaging with both three-dimensional (3D) CBCT and two-dimensional (2D) panoramic radiography. In all the images, the number of teeth with intracoronal resorption, affected tooth type and number, and size and location of the PIR defects were recorded. The McNemar test was used to compare the prevalence of PIR in the CBCT and panoramic images. RESULTS: Fewer PIR defects were detected in the panoramic images (3.1% of the patients) than in the CBCT images (9.5% of the patients) (p< .001). According to the CBCT images, the distribution of PIR defects was as follows: third molars (59.5%), canine teeth (11.4%), second molars and premolars (7.6% for both), supernumerary teeth (5.1%), second molars (3.8%), central incisors (2.5%), and first premolar and primary second molar teeth (1.5% for both). According to the scoring classification system for PIR defects, PIR 1 defects were the most common (65.8%), followed by PIR 3 (24.1%) and PIR 2 (10.1%). Of these defects, 69.6% were located in the central aspect of the crown. Ectopically positioned teeth showing intracoronal resorption accounted for 51.9% of the cases of PIR. CONCLUSIONS: CBCT detected more cases of PIR than panoramic radiography. The mandibular third permanent molar was the most commonly affected tooth. PMID- 27669815 TI - Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity. AB - Natural products guttiferone A, hyperforin, and aristoforin were able to inhibit or increase SIRT1 catalytic activity, depending on protein concentration and presence of detergent. On the basis of NMR data for guttiferone A, we demonstrated that the aggregation state of the natural product played a crucial role for its interaction with the enzyme. These results are useful to interpret future in vitro structure-activity relationship studies on these natural products in the quest of their biological target(s). PMID- 27669816 TI - Rapid Covalent Immobilization of Proteins by Phenol-Based Photochemical Cross Linking. AB - A strategy for photoinduced covalent immobilization of proteins on phenol functionalized surfaces is described. Under visible light irradiation, the reaction can be completed within seconds at ambient temperature, with high yields in aqueous solution of physiological conditions. Protein immobilization is based on a ruthenium-catalyzed radical cross-linking reaction between proteins and phenol-modified surfaces, and the process has proven mild enough for lipase, Staphylococcus aureus protein A, and streptavidin to preserve their bioactivity. This strategy was successfully applied to antibody immobilization on different material platforms, including agarose beads, cellulose membranes, and glass wafers, thus providing a generic procedure for rapid biomodification of surfaces. PMID- 27669817 TI - Association between dietary patterns and low bone mineral density among adults aged 50 years and above: findings from the North West Adelaide Health Study (NWAHS). AB - Studies on the association between dietary patterns and bone mineral density (BMD) have reported inconsistent findings. Data from the North West Adelaide Health Study, a population-based cohort study undertaken in Australia, were used to assess this association among adults aged 50 years and above. In this specific study, 1182 adults (545 males, 45.9 %) had dietary data collected using a FFQ and also had BMD measurements taken using dual-energy X-ray absorptiometry. Factor analysis with principal component method was applied to ascertain dietary patterns. Two distinct dietary patterns were identified. Pattern 1 ('prudent pattern') was characterised by high intake of fruits, vegetables, sugar, nut based milk, fish, legumes and high-fibre bread. In contrast, pattern 2 ('Western pattern') was characterised by high levels of processed and red meat, snacks, takeaway foods, jam, beer, soft drinks, white bread, poultry, potato with fat, high-fat dairy products and eggs. Compared with the study participants in the first tertile (T1, lowest consumption) of the prudent pattern, participants in the third tertile (T3) had a lower prevalence of low BMD (prevalence ratio (PR)=0.52; 95 % CI 0.33, 0.83) after adjusting for socio-demographic, lifestyle and behavioural characteristics, chronic conditions and energy intake. Participants in T3 of the Western pattern had a higher prevalence of low BMD (PR=1.68; 95 % CI 1.02, 2.77) compared with those in T1. In contrast to the Western diet, a dietary pattern characterised by high intake of fruits, vegetables and dairy products is positively associated with BMD. PMID- 27669819 TI - Schizo-obsessive spectrum disorders: an update. AB - The presence of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorders (OCD) in schizophrenia is frequent, and a new clinical entity has been proposed for those who show the dual diagnosis: the schizo-obsessive disorder. This review scrutinizes the literature across the main academic databases, and provides an update on different aspects of schizo-obsessive spectrum disorders, which include schizophrenia, schizotypal personality disorder (SPD) with OCD, OCD with poor insight, schizophrenia with OCS, and schizophrenia with OCD (schizo obsessive disorder). An epidemiological discussion on the discrepancies observed in the prevalence of OCS and OCD in schizophrenia across time is provided, followed by an overview of the main clinical and phenomenological features of the disorder in comparison to the primary conditions under a spectral perspective. An updated and comparative analysis of the main genetic, neurobiological, neurocognitive, and pharmacological treatment aspects for the schizo-obsessive spectrum is provided, and a discussion on endophenotypic markers is introduced in order to better understand its substrate. There is sufficient evidence in the literature to demonstrate the clinical relevance of the schizo-obsessive spectrum, although little is known about the neurobiology, genetics, and neurocognitive aspects of these groups. The pharmacological treatment of these patients is still challenging, and efforts to search for possible specific endophenotypic markers would open new avenues in the knowledge of schizo obsessive spectrum. PMID- 27669818 TI - A minor but deadly surgery of colonic polypectomy in an elderly and fragile patient: a case report and the review of literature. AB - BACKGROUND: Epithelial dysplasia and adenomatous polyps of colorectum are precancerous lesions. Surgical removal is still one of the important treatment approaches for colorectal polyps. CASE PRESENTATION: A male patient over 78 years was admitted due to bloody stool and abdominal pain. Colonoscopic biopsy showed a high-grade epithelial dysplasia in an adenomatous polyp of sigmoid colon. Anemia, COPD, ischemic heart disease (IHD), arrhythmias, and hypoproteinemia were comorbidities. The preoperative preparation was carefully made consisting of oral nutritional supplements (ONS), blood transfusion, cardiorespiratory management, and hemostatic therapy. However, his illness did not improve but deteriorate mainly due to polyp rebleeding during preparative period. The open polypectomy was performed within 60 min under epidural anesthesia. Postoperative treatments included oxygen inhalation, bronchodilation, parenteral and enteral nutrition, human serum albumin, antibiotics, and blood transfusion. Unluckily, these did not significantly facilitate to surgical recovery on account of severe comorbidities and complications. The most serious complications were colonic leakage and secondary abdominal severe infection. The patient finally gave up treatment due to multiple organ dysfunction syndromes. CONCLUSIONS: The polypectomy for colonic polyp is a seemingly minor but potentially deadly surgery for patients with severe comorbidities, and prophylactic ostomy should be considered for the safety. PMID- 27669820 TI - The similar and different evolutionary trends of MATE family occurred between rice and Arabidopsis thaliana. AB - BACKGROUND: Multidrug and toxic compound extrusion (MATE) transporter proteins are present in all organisms. Although the functions of some MATE gene family members have been studied in plants, few studies have investigated the gene expansion patterns, functional divergence, or the effects of positive selection. RESULTS: Forty-five MATE genes from rice and 56 from Arabidopsis were identified and grouped into four subfamilies. MATE family genes have similar exon-intron structures in rice and Arabidopsis; MATE gene structures are conserved in each subfamily but differ among subfamilies. In both species, the MATE gene family has expanded mainly through tandem and segmental duplications. A transcriptome atlas showed considerable differences in expression among the genes, in terms of transcript abundance and expression patterns under normal growth conditions, indicating wide functional divergence in this family. In both rice and Arabidopsis, the MATE genes showed consistent functional divergence trends, with highly significant Type-I divergence in each subfamily, while Type-II divergence mainly occurred in subfamily III. The Type-II coefficients between rice subfamilies I/III, II/III, and IV/III were all significantly greater than zero, while only the Type-II coefficient between Arabidopsis IV/III subfamilies was significantly greater than zero. A site-specific model analysis indicated that MATE genes have relatively conserved evolutionary trends. A branch-site model suggested that the extent of positive selection on each subfamily of rice and Arabidopsis was different: subfamily II of Arabidopsis showed higher positive selection than other subfamilies, whereas in rice, positive selection was highest in subfamily III. In addition, the analyses identified 18 rice sites and 7 Arabidopsis sites that were responsible for positive selection and for Type-I and Type-II functional divergence; there were no common sites between rice and Arabidopsis. Five coevolving amino acid sites were identified in rice and three in Arabidopsis; these sites might have important roles in maintaining local structural stability and protein functional domains. CONCLUSIONS: We demonstrate that the MATE gene family expanded through tandem and segmental duplication in both rice and Arabidopsis. Overall, the results of our analyses contribute to improved understanding of the molecular evolution and functions of the MATE gene family in plants. PMID- 27669821 TI - Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: a Spanish expanded access trial. AB - BACKGROUND: Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML. METHODS: This was a Spanish expanded access trial including patients aged >=18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy. RESULTS: Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3-10.9) months. Eleven (57.9 %) remained on 10 mg/day throughout the study and eight (42.1 %) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1 %) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3 %) was serious (pneumonia). AML volume was reduced >=30 % in 11 (57.9 %) patients and >=50 % in 9 (47.4 %); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively. CONCLUSIONS: These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes. TRIAL REGISTRATION: EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012. PMID- 27669823 TI - Recruitment of older adults with type 2 diabetes into a community-based exercise and nutrition randomised controlled trial. AB - BACKGROUND: Recruitment of participants into long-term community-based lifestyle intervention trials, particularly adults with a chronic disease, is often slow and challenging. Currently there is limited data on successful recruitment strategies suitable for older adults with type 2 diabetes into community-based exercise and nutrition programs, and no information on cost estimates associated with such recruitment. The aim of this report is to describe the recruitment strategies used and the success of each approach in recruiting older adults with type 2 diabetes into a 6-month community-based exercise and nutritional supplementation randomised controlled trial (RCT). A secondary aim is to assess the costs associated with the recruitment methods used. METHODS: The Resistance Exercise, Vitamin D and Muscle Protein Intervention Trial (REVAMP-IT) for type 2 diabetes is a 24-week RCT targeting 202 adults with type 2 diabetes which is designed to evaluate whether post-exercise ingestion of a whey- protein and vitamin D-enriched drink can enhance the effects of progressive resistance training (PRT) on glycaemic control, body composition and cardiometabolic health. Participants in this trial were randomly allocated to either: (1) the Lift for Life(r) community-based PRT program combined with additional whey protein and vitamin D, or (2) the Lift for Life(r) PRT program alone. Recruitment strategies included state and local newspaper and radio advertisements, targeted mail-outs, doctor and allied health referrals, community presentations, web-based media and word of mouth. The number of expressions of interest, participants screened and included in the trial, and how they first heard about the study were recorded by research staff during the screening process. Reasons for ineligibility or non participation in the trial were also recorded as was the cost of each recruitment method used. RESULTS: A total of 1157 expressions of interest were received over a 21-month recruitment period. Overall 959 (83 %) individuals were screened and found to be ineligible for the trial or chose not to participate or could not be contacted further following their initial enquiry. As a result, 198 participants were randomised to the 24-week intervention. The most effective recruitment strategies were targeted mass mail-outs (39 % of the total participant sample), state (27 %) and local (14 %) print media. In total recruitment expenditure was AUD$40,421, which equated to AUD$35 per enquiry and AUD$204 per eligible participant. Targeted mail-outs and state print media were the most expensive strategies each accounting for 38 % of total expenditure. CONCLUSIONS: To recruit around 200 older adults with type 2 diabetes into a community-based lifestyle intervention trial in a timely manner, it is important to ensure that an adequate budget is allocated to recruitment as targeted mail-outs and state/local print media were the most costly but effective strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference ACTRN12613000592741 . Registered on 27 May 2013. PMID- 27669824 TI - Multistacking from Two Sample Streams in Nonaqueous Microchip Electrophoresis. AB - The translation of stacking techniques used in capillary electrophoresis (CE) to microchip CE (MCE) in order to improve concentration sensitivity is an important area of study. The success in stacking relies on the generation and control of the stacking boundaries which is a challenge in MCE because the manipulation of solutions is not as straightforward as in CE with a single channel. Here, a simple and rapid online sample concentration (stacking strategy) in a battery operated nonaqueous MCE device with a commercially available double T-junction glass chip is presented. A multistacking approach was developed in order to circumvent the issues for stacking in nonaqueous MCE. The cationic analytes from the two loading channels were injected under field-enhanced conditions and were focused by micelle-to-solvent stacking. This was achieved by the application of high electric fields along the two loading channels and a low electric field in the separation channel, with one ground electrode in the reservoir closest to the junction. At the junction, the stacked zones were restacked under field-enhanced conditions and then injected into the separation channels. The multistacking was verified under a fluorescence microscope using Rhodamine 6G as the analyte, revealing a sensitivity enhancement factor (SEF) of 110. The stacking approach was also implemented in the nonaqueous MCE with contactless conductivity detection of the anticancer drug tamoxifen as well as its metabolites. The multistacking and analysis time was 40 and 110 s, respectively, the limit of detections was from 10 to 35 ng/mL and the SEFs were 20 to 50. The method was able to quantify the target analytes from breast cancer patients. PMID- 27669822 TI - Cross-cultural comparison of perspectives on healthy eating among Chinese and American undergraduate students. AB - BACKGROUND: Understanding views about what constitutes a healthy diet in diverse populations may inform design of culturally tailored behavior change interventions. The objective of this study was to describe perspectives on healthy eating among Chinese and American young adults and identify similarities and differences between these groups. METHODS: Chinese (n = 55) and American (n = 57) undergraduate students in Changsha, Hunan, China and Honolulu, Hawai'i, U.S.A. composed one- to two-paragraph responses to the following prompt: "What does the phrase 'a healthy diet' mean to you?" Researchers used content analysis to identify predominant themes using Dedoose (version 5.2.0, SocioCultural Research Consultants, LLC, Los Angeles, CA, 2015). Three researchers independently coded essays and grouped codes with similar content. The team then identified themes and sorted them in discussion. Two researchers then deductively coded the entire data set using eight codes developed from the initial coding and calculated total code counts for each group of participants. RESULTS: Chinese students mentioned physical outcomes, such as maintaining immunity and digestive health. Timing of eating, with regular meals and greater intake during day than night, was emphasized. American students described balancing among food groups and balancing consumption with exercise, with physical activity considered essential. Students also stated that food components such as sugar, salt and fat should be avoided in large quantities. Similarities included principles such as moderation and fruits and vegetables as nutritious, and differences included foods to be restricted and meal timing. While both groups emphasized specific foods and guiding dietary principles, several distinctions in viewpoints emerged. CONCLUSIONS: The diverse views may reflect food-related messages to which participants are exposed both through the media and educational systems in their respective countries. Future studies may further examine themes that may not typically be addressed in nutrition education programs in diverse populations of young adults. Gaining greater knowledge of the ways in which healthy eating is viewed will allow for development of interventions that are sensitive to the traditional values and predominant views of health in various groups. PMID- 27669826 TI - DRG2 Regulates G2/M Progression via the Cyclin B1-Cdk1 Complex. AB - Developmentally regulated GTP-binding protein 2 (DRG2) plays an important role in cell growth. Here we explored the linkage between DRG2 and G2/M phase checkpoint function in cell cycle progression. We observed that knockdown of DRG2 in HeLa cells affected growth in a wound-healing assay, and tumorigenicity in nude mice xenografts. Flow cytometry assays and [(3)H] incorporation assays indicated that G2/M phase arrest was responsible for the decreased proliferation of these cells. Knockdown of DRG2 elicited down-regulation of the major mitotic promoting factor, the cyclin B1/Cdk1 complex, but up-regulation of the cell cycle arresting proteins, Wee1, Myt1, and p21. These findings identify a novel role of DRG2 in G2/M progression. PMID- 27669827 TI - Bioemulsifier (BE-AM1) produced by Solibacillus silvestris AM1 is a functional amyloid that modulates bacterial cell-surface properties. AB - A novel estuarine bacterial strain, Solibacillus silvestris AM1, produces an extracellular, thermostable and fibrous, glycoprotein bioemulsifier (BE-AM1). The amyloid nature of the bioemulsifier (BE-AM1) was confirmed by biophysical techniques (Congo red based polarization microscopy, ThioflavinS based fluorescent microscopy, fibrous arrangement in transmission electron microscopy and secondary structure measurement by FTIR and CD spectrum analysis). Cell-bound BE-AM1 production by S. silvestris AM1 during the mid-logarithmic phase of growth coincided with a decrease in cell surface hydrophobicity, and an increase in cell autoaggregation and biofilm formation. It was observed that the total interfacial interaction energy ([Formula: see text]) for the surface of the bioemulsifier producing S. silvestris AM1 and different derivatized surfaces of polystyrene (silanized and sulfonated) was found to support biofilm formation. This study has revealed that the BE-AM1, a bacterial bioemulsifier, is a functional amyloid and has a role in biofilm formation and cell surface modulation in S. silvestris AM1. PMID- 27669825 TI - Protein Phosphatases Involved in Regulating Mitosis: Facts and Hypotheses. AB - Almost all eukaryotic proteins are subject to post-translational modifications during mitosis and cell cycle, and in particular, reversible phosphorylation being a key event. The recent use of high-throughput experimental analyses has revealed that more than 70% of all eukaryotic proteins are regulated by phosphorylation; however, the mechanism of dephosphorylation, counteracting phosphorylation, is relatively unknown. Recent discoveries have shown that many of the protein phosphatases are involved in the temporal and spatial control of mitotic events, such as mitotic entry, mitotic spindle assembly, chromosome architecture changes and cohesion, and mitotic exit. This implies that certain phosphatases are tightly regulated for timely dephosphorylation of key mitotic phosphoproteins and are essential for control of various mitotic processes. This review describes the physiological and pathological roles of mitotic phosphatases, as well as the versatile role of various protein phosphatases in several mitotic events. PMID- 27669830 TI - Welcome to Bournemouth '94. AB - Welcome to the 1994 RCN Congress Exhibition and Jobs Fair. This special supplement provides an overview of the Congress, highlights from the agenda and a detailed listing of all of the exhibitors. Bournemouth 94 is now the single biggest event in the nursing calendar. For the career minded nurse, the RCN Congress and Exhibition is a must. PMID- 27669829 TI - Chronic Intestinal Pseudo-obstruction: Clinical and Manometric Characteristics in the Chilean Population. AB - Background/Aims: Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by a failure of the propulsion of intraluminal contents and recurrent symptoms of partial bowel obstruction in the absence of mechanical obstruction. Regional variations of the intestinal compromise have been described. Intestinal manometry can indicate the pathophysiology and prognosis. Our objective is to establish the demographic and clinical characteristics of group Chilean patients and analyze the motility of the small intestine and its prognostic value. Methods: Patients with symptoms of intestinal pseudo obstruction with dilated bowel loops were included, in all of whom a manometry of the small intestine was performed using perfused catheters. Results: Of the 64 patients included, 51 women (average age 41.5 +/- 17.6 years), 54 primary and 10 secondary CIPO were included. Dilatation of the small intestine was the only finding in 38 patients; in the remaining, the compromise was associated with other segments, primarily the colon. Forty-nine patients underwent 65 surgeries, mainly exploratory laparotomies and colectomies. Intestinal manometry was performed on all patients; 4 "patterns" were observed: neuropathic (n = 26), myopathic (n = 3), mixed (n = 24), and a group without motor activity (n = 11). The most relevant findings were the complex migrating motor disorders and decreased frequency and propagation of contractions. The 9 patients who died had a severe myopathic compromise. Conclusions: In our series, isolated small bowel compromise was the most common disorder. Neuropathic motor compromise was observed in most of the patients. Mortality was associated with severe myopathic compromise. PMID- 27669828 TI - Weight change trends and overall survival in United States veterans with follicular lymphoma treated with chemotherapy. AB - Understanding weight change patterns in follicular lymphoma (FL) may be important for the assessment of prognosis as well as the long-term care of survivors. A retrospective cohort of United States veterans with a new diagnosis of FL between October 1, 1998 and September 30, 2010 was assembled. Weight changes were evaluated before, during, and after treatment in 896 FL patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without rituximab (CHOP +/- R); cyclophosphamide, vincristine, and prednisone, with or without rituximab (CVP +/- R); or rituximab monotherapy. Weight decreased an average of 1.4 kg during therapy, and >5% weight loss during this time period was associated with worse overall survival. Weight increased to an average of 1.4 kg above baseline by 24 months after treatment initiation, with 15% gaining greater than 10% of their baseline weight. Weight management strategies may be an important part of long-term survivorship planning. PMID- 27669831 TI - ? AB - There have been many 'visions' of nursing, and now the profession is being asked to look towards the challenges for nursing and midwifery in the 21st century in a new document from the four UK Chief Nursing Officers. In the face of massive change, says the document, there will be 'an urgent need for a new view of the role of nursing across the board'. PMID- 27669834 TI - Red Cross trio in Rwanda capital. AB - A British Red Cross nurse arrived in the besieged capital of Rwanda last week as part of an international relief effort in the African country. PMID- 27669833 TI - The silence of the lambs. AB - Driving home the other day I noticed Suffolk ewes and their bedraggled lambs in the fields around Penrith, rather like fleecy islands amongst the large portions of the Irish Sea which currently fill up the rest of the low lying fields. PMID- 27669835 TI - College seeks Bottomless assurance over job titles dispute. AB - The Royal College of Nursing is seeking an assurance from health secretary Virginia Bottomley that qualified nurses will be allowed to keep their job titles when trusts introduce new systems such as Patient Focused Care. PMID- 27669836 TI - Sweeping change in nurse roles forecast. AB - A vision of nursing in the 21st century has been unveiled by the United Kingdom's Chief Nursing Officers and leading nurses. PMID- 27669837 TI - RCN Congress to hear decision on nurse prescribing. AB - Junior health minister Baroness Cumberlege (right) is expected to make announcements on nurse prescribing and funding for the Post-registration Education and Practice initiative when she addresses the Royal College of Nursing Congress in Bournemouth next week. PMID- 27669838 TI - Confusion over implementing Clothier recommendations. AB - An internal hospital memo warning of the risks of employing 'someone with murderous tendencies' has highlighted the confusion and lack of guidance over how hospitals should deal with the recommendations of the Clothier report . PMID- 27669839 TI - RCN subscription rates should be linked to inflation. AB - The RCN has deferred until July any decision on automatic subscription increases. PMID- 27669840 TI - Extra L1.6 billion should finance pay award, says RCN. AB - The Government should fund the 3 per cent pay increase awarded last month to nurses from the L1.6 billion increase in NHS funding, RCN Council agreed. PMID- 27669841 TI - Opposition to all-graduate recruitment expected as RCN considers education issues. AB - A task force is to be set up to take forward the findings of the Royal College of Nursing's Future of Nursing Education Consensus Conference held last September. PMID- 27669842 TI - Blowing your own trumpet. AB - Nursing Standard have telephoned, please ring back today, the note reads. Yes, it's that time of year, as the RCN is getting ready to 'go on the road' and Nursing Standard prepares the Congress edition of the journal. Congress seems to come around more quickly each year, this could be a sign of a busy life, or more probably ageing, it seems to be only weeks since I put away my Harrogate memorabilia and emptied the carrier bags! Now it is time to start preparing and packing for Bournemouth and Questions of Health', a contemporary theme for this years Congress. PMID- 27669843 TI - Donation deferred. AB - The RCN has deferred a decision on whether to donate L1,500 for renowned US nurse Virginia Henderson to live in a supported community setting. PMID- 27669844 TI - A year to be proud of. AB - The eve of RCN Congress 94 offers an important opportunity for reflecting on the achievements of the last year. And there have indeed been achievements, despite continuing pressures at work for all nurses. Perhaps most significantly, the RCN welcomed its 300,000th member. A small step in terms of statistics, this represents a giant step for nursing, once more confirming the RCN's position as the world's largest and most diverse professional organisation for nurses and the UK's sixth largest union. PMID- 27669845 TI - ? AB - Donkey work: 'The ward round' by Achille Formis, is one of the paintings on show at the Wellcome Foundation in Euston Road, London NW1, as part of the Look out! exhibition which 'explores experiences on the edge'. It moves to Berkshire on April 27. PMID- 27669846 TI - Plans to cut 13,000 beds in Scotland. AB - The NHS in Scotland is looking to cut 5,000 beds from the acute sector 'as soon as possible' and 8,000 long-stay beds from the end of the century. PMID- 27669848 TI - ENB members back chief executive. AB - English National Board Chief Executive Tony Smith has received messages of support from all ENB members in response to an anonymous letter calling for his resignation. PMID- 27669849 TI - Unions alarmed at 'ageism' in health service treatment. AB - Nursing unions have expressed alarm over reports that two elderly patients were refused hospital treatment because of their age. PMID- 27669850 TI - The year that was. AB - Calls for improvements in child protection proved to be a hot topic on the 1993 Congress agenda and the College's Child Protection Special Interest Group has now produced guidance, aimed particularly at student nurses, which will be available at this year's Congress. And following publication of the Clothier Inquiry report into the Allitt tragedy, the RCN launched a new publication on The Care of Sick Children: A Review of the Guidelines in the Wake of the Allitt Inquiry which will also be available in Bournemouth. PMID- 27669851 TI - Sleepless in London. AB - This year the RCN Congress and exhibition returns to Bournemouth for the first time since 1985. It was the year that the Representative Body was re-named Congress and the first year that the event was given a slogan. That year Congress was coming 'Out of the shell' and in the nine years since we were last in Bournemouth the event has evolved and blossomed into the most significant conference and exhibition in the nursing calendar. PMID- 27669852 TI - Nurses confused over role of HCAs. AB - Newly qualified nurses have difficulty defining the differences between their roles and those of health care assistants, a researcher has claimed. PMID- 27669854 TI - Sister role no substitute for team spirit. AB - The cohesion of the ward team may have greater potential as a predictor of the effectiveness ot nursing care than the teambuilding skills of the ward sister, a study has suggested. PMID- 27669853 TI - Hospice nurses with support less likely to use 'blocking'. AB - Hospice nurses are less likely to use 'blocking' tactics with patients if they feel they are supported by their ward sisters, a study has shown. PMID- 27669855 TI - Research still dominated by doctors. AB - Nursing has an important contribution to make to multidisciplinary health services research, but there are difficulties in ensuring the nursing dimension is clearly defined, the conference heard. PMID- 27669856 TI - Teachers unclear about their Project 2000 clinical status. AB - Research commissioned by the English National Board shows nurse teachers feel unable to practise in clinical areas with credibility, and they disagree about whether Project 2000 I requires them to spend more or less time in clinical areas. PMID- 27669857 TI - Patients divided over first name terms. AB - A 'substantial minority' of hospital patients do not wish to be referred to by their first names, research carried out in Manchester has shown. PMID- 27669858 TI - Exhibitor list/stand no. PMID- 27669859 TI - Stress blamed for absenteeism. AB - Nursing unions have blamed macho managers and the pace of change in the NHS for high nurse sickness levels uncovered by an Audit Commission report published last week. It claimed the NHS could save up to L180 million a year by better management of nurse sickness. PMID- 27669860 TI - Parliament. AB - Health minister Dr Brian Mawhinney has confirmed in the Commons that the UKCC's Code of Professional Conduct does take precedence over the NHS Executive's guidelines on staff relations with the public and the media. PMID- 27669861 TI - Firm appointments aim in Patients Charter. AB - Community nurses will be required to set firm appoint-ments times as apart of the Patients' Charter, health secretary Virginia Bottomley announced last week. Mrs Bot-tomley said the introduction of timed appointment was a part of the 'expansion' and improvement of the Charter standards. PMID- 27669863 TI - Study reveals failure in identification of women at risk from alcohol abuse. AB - Health professionals may be failing to recognise and treat women with serious alcohol problems, researchers have suggested. PMID- 27669862 TI - The history of the RCN congress. AB - The RCN Congress started life in 1924 when the Annual General Meeting (AGM) was held, on 26th June, in the Hall, Mortimer Street, at 3-0 pm, a 'public conference' was held that in the Lecture Theatre of the Hospital. The title of the confer- was 'What is an Ideal Nursing service. PMID- 27669865 TI - Hospital staff lack nutritional skills. AB - Patients' nutritional needs are often neglected in hospital, with many losing weight due to staffs lack of knowledge of clinical nutrition, researchers in Scotland have claimed. PMID- 27669864 TI - Women 'should be screened for incontinence'. AB - Women attending for cervical smear tests should be screened for and advised about urinary incontinence, researchers in Bristol have suggested. PMID- 27669866 TI - Congress Agenda at a glance. AB - 1 UKCC elections Submitted by the RCN Society of Orthopaedic Nursing. That this meeting of the RCN Congress discusses the future structure of UKCC elections and RCN strategy for future election campaigns. PMID- 27669868 TI - Fluid balance during hysteroscopic surgery. AB - Researchers from the The Netherlands have devised an accurate and cheap solution for monitoring for fluid overload during hysteroscopic surgery. PMID- 27669867 TI - Short antibiotic courses save money. AB - Major savings could be made in the drugs' budget if GPs prescribed antibiotics for five rather than seven days. PMID- 27669870 TI - Alternative to liver transplant in children? AB - A call for a controlled study to determine whether liver transplant is better than medical treatment for fulminant hepatic failure has been made by Japanese researchers. PMID- 27669869 TI - Pollution and hay fever link questioned. AB - The incidence of hay fever shows no consistent upward trend and local pollution is unlikely to affect the incidence greatly, Birmingham researchers report. PMID- 27669871 TI - Reviewing the Agenda. AB - By the end of next week RCN Congress could have agreed to call for cannabis to be decriminalised, for smokers to pay for treatment of smoking-related illnesses and for the introduction of equal ages of consent for hetero and homosexuals. PMID- 27669872 TI - Decriminalising drugs. AB - RCN Congress last year saw one of its most volatile debates - around a matter for discussion on the issue of decriminalisation of drugs. There is no doubt this is an issue which can polarise opinion. PMID- 27669873 TI - An agenda for nurse leaders. AB - The health service's new ' chief executive, Alan Langlands, is now in place. Also in place, perhaps surprisingly, is his broad strategy for the future of nursing management. Mr Langlands officially took up his post as Chief Executive of the NHS Management Executive (ME) on the first of this montli and has given every indication of his enthusiasm to stop nursing drifting into the policy doldrums that have threatened it over recent years. While there have been nursing initiatives aplenty since the beginning of the NHS marketplace changes, many now languish on forgotten shelves through lack of central will, pushed aside by the latest 'urgent' ministerial agenda. Remember the original Strategy for Nursing? PMID- 27669874 TI - Hay bailed out by student support.. AB - I read with some relief the article by Robert Hay on nursing research (A nurse's place..., Viewpoint, March 30). PMID- 27669875 TI - ? AB - * On reading 'A nurse's place...', I was incensed. I was shocked to think we had such small-minded, uninformed and sexist members of our profession. I was therefore relieved to note that the author was not a nurse, but a consultant surgeon. PMID- 27669876 TI - ...but condemned by others. AB - Far from taking an unbiased interest in the development of the nursing profession, Mr Hay sadly undermines any valuable contribution that research-based care could bring to the benefit of patients. PMID- 27669877 TI - Angry and hard up - a student's lot. AB - I am a student nurse undertaking a Project 2000 diploma at Portsmouth University. In common with other students, I receive a bursary for the duration of the three year course. PMID- 27669878 TI - Nurses' needs ignored in study day scam. AB - After attending a recent study day, we wish to alert our nursing colleagues to a negative aspect of consumerism in the NHS. PMID- 27669879 TI - Axed nurse gets little support. AB - I wrote to you recently about the abolition of the title 'matron', except in nursing homes, and had a satisfactory reply which said the title was retained there because it signified who was who. PMID- 27669880 TI - Therapeutic touch: the debate goes on. AB - We take exception to Jean Sayer-Adams' ad hominem arguments regarding the Skeptical Inquirer (Letters, April 6. Therapeutic touch: a nursing function, Clinical, January19). PMID- 27669881 TI - Information exchange. AB - I am a district nurse student researching the use of nursing assessments in the community. I would be grateful for any information on this subject, particularly copies of health authority/trust assessment forms and information about where assessment forms are kept, eg, at a base or in the client's home, and your views on this. PMID- 27669882 TI - Gossip. AB - * Brighton Health Care NHS Trust has produced a very worthy booklet detailing action taken on suggestions to improve the lot of patients and staff. Among the 138 ideas received, 'The chairman should purchase a second suit and bin the tatty blue pinstripe which gives us a bad image.' Agreed,' says the managers' response. 'The chairman hits now purchased a second new suit at his own expense.' Good to know democracy in the NHS is not dead. PMID- 27669883 TI - Mother russia. PMID- 27669884 TI - Oropharyngeal dysphagia in children with cerebral palsy: comparisons between a high- and low-resource country. AB - PURPOSE: There is paucity of research investigating oropharyngeal dysphagia (OPD) in young children with cerebral palsy (CP), and most studies explore OPD in high resource countries. This study aimed at determining the proportion and severity of OPD in preschool children with CP in Bangladesh, compared to Australia. METHOD: Cross-sectional, comparison of two cohorts. Two hundred and eleven children with CP aged 18-36 months, 81 in Bangladesh (mean = 27.6 months, 61.7% males), and 130 in Australia (mean = 27.4 months, 62.3% males). The Dysphagia Disorders Survey (DDS) - Part 2 was the primary OPD outcome for proportion and severity of OPD. Gross motor skills were classified using the Gross Motor Function Classification System (GMFCS), motor type/distribution. RESULTS: (i) Bangladesh sample: proportion OPD = 68.1%; severity = 10.4 SD = 7.9. Australia sample: proportion OPD = 55.7%; severity = 7.0 SD = 7.5. (ii) There were no differences in the proportion or severity of OPD between samples when stratified for GMFCS (OR = 2.4, p = 0.051 and beta = 1.2, p = 0.08, respectively). CONCLUSIONS: Despite overall differences in patterns of OPD between Bangladesh and Australia, proportion and severity of OPD (when adjusted for the functional gross motor severity of the samples) were equivalent. This provides support for the robust association between functional motor severity and OPD proportion/severity in children with CP, regardless of the resource context. Implications for Rehabilitation The proportion and severity of OPD according to gross motor function level were equivalent between high- and low-resource countries (LCs). Literature from high-resource countries may be usefully interpreted by rehabilitation professionals for low-resource contexts using the GMFCS as a framework. The GMFCS is a useful classification in LCs to improve earlier detection of children at risk of OPD and streamline management pathways for optimal nutritional outcomes. Rehabilitation professionals working in LCs are likely to have a caseload weighted towards GMFCS III-V, with less compensatory OPD management options available (such as non-oral nutrition through tubes). PMID- 27669885 TI - Use of platelet concentrates in oral and maxillofacial surgery: an overview. AB - OBJECTIVE: To describe and provide a comprehensive overview on the development, use and efficacy of autologous platelet concentrates in different in vitro and in vivo studies focusing on oral and maxillofacial pathologies. MATERIALS AND METHODS: Present work employs an extensive critical overview of the literature on the development and application of platelet concentrates. RESULTS: Platelet concentrates are innovative endogenous therapeutic agents which gained a lot of interest in different medical and dental disciplines due to their potential ability to stimulate and increase regeneration of soft and hard tissues. The effect of platelet-derived products is considered to be a result of the high number of platelets which contain a wide range of growth factors. They are not just therapeutic products but autologous blood concentrates containing active molecules. The quality of platelet concentrates may vary according to the individual physical state of donors making it difficult to to compare the outcomes of their application. Although, there are many studies analyzing the properties of these biomaterials both in vivo and in vitro, a consensus regarding their efficacy still has to be reached. CONCLUSION: Evidences described in the literature on the efficacy of platelet concentrates in procedures in oral and maxillofacial region are controversial and limited. In order to clarify the real advantages and priorities for the patients, when the blood-derived products are applied, further in vitro and in vivo research about the activity of PRP and PRF on the dental cells biology should be conducted. PMID- 27669886 TI - Morphology and molecular analysis of Oncicola venezuelensis (Acanthocephala: Oligacanthorhynchidae) from the ocelot Leopardus pardalis in Brazil. AB - Oncicola venezuelensis Marteau, 1977 was found parasitizing adults of Leopardus pardalis (Linnaeus) found dead in Serra da Capivara National Park, Piaui state, Brazil, a new geographical locality reported for the species. The diversity of Oncicola Travassos, 1916 species is large, but genetic data are scarce. This article presents the results of genetic, morphological and ultrastructural studies carried out for taxonomic purposes. The first ultrastructural view showed a globular, short proboscis with 36 hooks, divided into six longitudinal rows of six hooks each. Hooks differ in size and shape: hooks I, II and III have a 'chisel-shaped' tip. The genetic profile included new sequences of ribosomal DNA ITS1, 5.8S and ITS2, and partial 28S rRNA regions. The results of maximum likelihood tree analyses for each region showed Oligacanthorhynchidae Southwell et Macfie, 1925 close to Gigantorhynchidae Hamann, 1892 (supported >91%). Both use mammals and birds as definitive hosts. Morphological and ultrastructural studies combined with genetic analysis shed more light on the diversity of Oncicola species. PMID- 27669887 TI - Group-Based Relaxation Response Skills Training for Pharmacologically-Resistant Depressed and Anxious Patients. AB - BACKGROUND: Drug-resistance for depression and anxiety is a major limitation in the treatment of these common disorders, and adjunct support interventions may be beneficial in the treatment of these patients. AIMS: The purpose of this study was to evaluate the effects of a short-term (8 session) Relaxation Response Skills Training (RRST) programme for a population of psychiatric outpatients with anxiety and mood disorders who were unresponsive to drug treatment, and to test the feasibility of this intervention as complementary treatment for a psychiatric setting. METHOD: Forty patients were measured for overall psychopathological symptoms, depression, and anxiety, and were then given an 8-week course of RRST, while continuing their pharmacological treatment. Following the RRST intervention, participants were again assessed. RESULTS: The results demonstrated reductions in overall symptoms (large effect size and reasonable clinically significant change), and also in depression and anxiety (medium effect sizes and clinically significant change). CONCLUSIONS: These results suggest that this short-term RRT offers a simple and cost-effective way to augment drug management for participants with common psychiatric disorders who are less responsive to the drug treatment. PMID- 27669888 TI - Micelles with Sheddable Dendritic Polyglycerol Sulfate Shells Show Extraordinary Tumor Targetability and Chemotherapy in Vivo. AB - Cancer nanomedicines are typically stealthed by a poly(ethylene glycol) layer that is important to obtain extended blood circulation and elevated tumor accumulation. PEG stealth, however, also leads to poor tumor cell selectivity and uptake thereby reducing treatment efficacy. Here, we report that biodegradable micelles with sheddable dendritic polyglycerol sulfate (dPGS) shells show an unusual tumor targetability and chemotherapy in vivo. The self-assembly of dPGS SS-poly(epsilon-caprolactone) amphiphilic block copolymer with an Mn of 4.8-3.7 kg mol-1 affords negatively charged and small sized micelles (dPGS-SS-PCL Ms). dPGS-SS-PCL Ms reveal a low cytotoxicity, decent doxorubicin (DOX) loading, and accelerated drug release under a reductive condition. Notably, DOX-loaded dPGS-SS PCL Ms exhibit a high tolerable dosage of more than 40 mg kg-1, a long plasma half-life of ca. 2.8 h, and an extraordinary tumor accumulation. Intriguingly, therapeutic results demonstrate that DOX-loaded dPGS-SS-PCL Ms induce complete tumor suppression, significantly improved survival rate, and diminishing adverse effects as compared to free drug (DOX.HCl) in MCF-7 human mammary carcinoma models. Dendritic polyglycerol sulfate with a superior tumor homing ability appears to be an attractive alternative to PEG in formulating targeted cancer nanomedicines. PMID- 27669889 TI - Comment on "Biosimilar FSH preparations- are they identical twins or just siblings?" PMID- 27669890 TI - Epidermal growth factor (EGF) receptor-ligand based molecular staging predicts prognosis in head and neck squamous cell carcinoma partly due to deregulated EGF- induced amphiregulin expression. AB - BACKGROUND: Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS: To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients. The intracellular signaling pathways controlling epidermal growth factor (EGF)-induced amphiregulin (AREG) expression were examined in three oral squamous cell carcinoma (OSCC) cell lines. Effect of AREG on cisplatin resistance was examined by viability assays in four-, and by association in 11 OSCC cell lines. RESULTS: The patients were divided into five groups according to the median mRNA expression levels of four EGFR ligands, i.e. AREG, EGF, heparin binding EGF-like growth factor (HBEGF) and beta-cellulin (BTC). The number of increased-expressed EGFR-ligands were progressively correlated to five-year survival, even in advanced TNM-stage IV patients, where five-year mortality increased from 26 % if tumor expressed none to one EGFR-ligand, to 45 % in three to four ligand expressing tumors. Thus, staging the tumor according to these EGFR ligand mRNA expression pattern completely out performed TNM staging in predicting prognosis. Multivariate analysis identified AREG as the dominating predictor, and AREG was overexpressed in OSCC compared to tumors from other sites. Both EGF and HBEGF stimulation induced strong AREG increase in OSCC cell lines, which was partially mediated by the extracellular signal-regulated kinase 1/2 pathway, and negatively regulated by p38, c-Jun N-terminal kinase, and phosphoinositide-3 kinase. Although increased AREG mRNA expression predicted unfavorable prognosis in platinum treated HNSCC patients, AREG did not mediate cisplatin resistance in the OSCC cell lines. CONCLUSIONS: Increased tumorous mRNA expression of four EGFR ligands was progressively associated with poor prognosis in HNSCC. Thus, EGFR ligands mRNA expression pattern may be a new prognostic biomarker. The tightly regulated EGF-induced AREG mRNA expression was partly lost in the OSCC cell lines and restoring its regulation may be a new target in cancer treatment. TRIAL REGISTRATION: Not applicable as the clinical data of the 498 HNSCC patients and their mRNA expression profiles were collected from the open TCGA database: http://cancergenome.nih.gov/cancersselected/headandneck . PMID- 27669892 TI - Beliefs and motives related to eating and body size: a comparison of high-BMI and normal-weight young adult women from rural and urban areas in Mexico. AB - BACKGROUND: Effective treatment and prevention of obesity and its co-morbidities requires the recognition and understanding of cultural and social aspects of eating practices. The objective of the present study was to identify social factors and beliefs that may explain undesirable eating practices among women with high body mass index (HBMI) compared with normal-weight (NW) women from rural and urban areas classified as middle-low socioeconomic status (SES) in the State of Queretaro, Mexico. METHODS: A qualitative technique with individual in depth interviews was used. Fifty-five women with either NW or HBMI from rural and urban areas participated in the study. The responses were analyzed by coding and grouping text fragments into categories in a data matrix, in order to make comparisons between BMI groups and between rural and urban women. RESULTS: The habit of skipping breakfast prevailed among women with HBMI who also reported childhood food deprivation. Feelings related to eating seemed to be more important than losing weight among women with HBMI from urban and rural areas. Thus, overweight might be interpreted as a social symbol of the enjoyment of a good life, primarily in rural areas. Overweight was socially accepted when it occurred in children and in married woman, mainly because it is a symbol of the good life that the head of the household provides, and also because women may feel more relaxed about their weight when they already have a partner. The study also revealed that women with HBMI were not sufficiently motivated to lose weight unless they experience a physical indication of poor health. CONCLUSION: The findings from this study are helpful in the understanding of the reasons why strategies for the prevention and treatment of obesity may not be as effective as expected. The belief system of particular social groups within different SESs should be considered in order to understand the etiology of obesity and develop effective strategies. PMID- 27669891 TI - A novel mutant allele of SSI2 confers a better balance between disease resistance and plant growth inhibition on Arabidopsis thaliana. AB - BACKGROUND: Resistance and growth are opposing characteristics in plants. SA INSENSITIVITY OF npr1-5 (SSI2) encodes a stearoyl-ACP desaturase (S-ACP DES) that has previously been reported to simultaneously enhance resistance and repress growth. RESULTS: Here, we characterize ssi2-2, a novel mutant allele of SSI2 that has two amino acid substitutions. Compared with wild-type and two other mutants of SSI2, ssi2-2 showed intermediate phenotypes in growth size, punctate necrosis, resistance to the bacterial pathogen Pst DC3000, salicylic acid (SA) content, pathogenesis-related (PR) gene levels and 18:1 content. These results indicate that ssi2-2 is a weak mutant of SSI2. Additionally, by using ssi2-2 as an intermediate control, a number of differentially expressed genes were identified in transcriptome profiling analysis. These results suggest that constitutive expression of defense-related genes and repression of IAA signaling-associated genes is present in all SSI2 mutants. CONCLUSIONS: Taken together, our results suggest that the weak ssi2-2 mutant maintains a better balance between plant immunity and vegetative growth than other mutants, consequently providing a basis to genetically engineer disease resistance in crop plants. PMID- 27669893 TI - How to design clinical rehabilitation trials for the upper paretic limb early post stroke? AB - BACKGROUND: The impact of spontaneous neurobiological recovery is still neglected in designing rehabilitation trials early post stroke. We aimed to investigate the impact of the timing of randomization and prognostic stratification on the required sample sizes that are needed to reveal significant intervention effects on upper limb function at 26 weeks after first-ever ischemic stroke. METHOD: Sample size calculations were based on a cohort study of 159 patients, using the Fugl-Meyer Assessment Upper Extremity and Action Research Arm Test as outcome measures (power = 80 %; two-tailed alpha = 0.05). We investigated different scenarios: random sampling of patients within five time intervals (stroke onset to 1, 3, 5, 8 and 12 weeks post stroke), and within stratified groups according to the presence or absence of voluntary extension of the thumb and/or two or more fingers at intake. RESULTS: The heterogeneity between outcome scores of patients, and subsequently the required sample sizes, increased from the first to the fifth time interval. Compared to the whole group, the sample sizes for both stratified groups (i.e., patients with and without Voluntary Finger Extension (VFE)) were lower. The required sample sizes for the patient group without VFE markedly increased when the time interval was broadened from 1 to 12 weeks post stroke, as opposed to the decrease seen for the group of patients with VFE. CONCLUSION: These results are fundamental for designing upper limb trials early post stroke. To prevent type II error, future upper limb trials should randomize patients at a fixed moment early post stroke and stratify patients according to their potential neurobiological recovery. TRIAL REGISTRATION: Netherlands Trial Registry, www.trialregister.nl , NTR1424 , registered on 27 August 2008. PMID- 27669894 TI - Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma. AB - Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons. We previously reported that loss of glutamate transporters (EAAC1 or GLAST) in mice leads to RGC degeneration that is similar to normal tension glaucoma and these animal models are useful in examining potential therapeutic strategies. Caloric restriction has been reported to increase longevity and has potential benefits in injury and disease. Here we investigated the effects of every-other-day fasting (EODF), a form of caloric restriction, on glaucomatous pathology in EAAC1-/- mice. EODF suppressed RGC death and retinal degeneration without altering intraocular pressure. Moreover, visual impairment was ameliorated with EODF, indicating the functional significance of the neuroprotective effect of EODF. Several mechanisms associated with this neuroprotection were explored. We found that EODF upregulated blood beta-hydroxybutyrate levels and increased histone acetylation in the retina. Furthermore, it elevated retinal mRNA expression levels of neurotrophic factors and catalase, whereas it decreased oxidative stress levels in the retina. Our findings suggest that EODF, a safe, non-invasive, and low-cost treatment, may be available for glaucoma therapy. PMID- 27669895 TI - Isolation, purification and analysis of dissolved organic carbon from Gohagoda uncontrolled open dumpsite leachate, Sri Lanka. AB - Extract and analysis of the Dissolved Organic Carbon (DOC) fractions were analyzed from the leachate of an uncontrolled dumpsite at Gohagoda, Sri Lanka. DOC fractions, humic acid (HA), fulvic acid (FA) and the hydrophilic (Hyd) fractions were isolated and purified with the resin techniques. Spectroscopic techniques and elemental analysis were performed to characterize DOCs. Maximum TOC and DOC values recorded were 56,955 and 28,493 mg/L, respectively. Based on the total amount of DOC fractionation, Hyd dominated accounting for ~60%, and HA and FA constituted ~22% and ~17%, respectively, exhibiting the mature phase of the dumpsite. The elemental analysis of DOCs revealed carbon variation following HA > FA > Hyd, while hydrogen and nitrogen were similar in each fraction. The N/C ratio for HA was recorded as 0.18, following a similar trend in old dumpsite leachate elsewhere. The O/C ratios for HA and FA were recorded higher as much as 1.0 and 9.3, respectively, indicating high degree of carbon mineralization in the leachates. High content of carboxylic, phenolic and lactone groups in all DOCs was observed disclosing their potential for toxic substances transportation. The results strongly suggest the risk associated with DOCs in dumpsite leachate to the aquatic and terrestrial environment. PMID- 27669896 TI - Using an Optical Probe as the Microdrop Holder in Headspace Single Drop Microextraction: Determination of Sulfite in Food Samples. AB - A novel headspace single-drop microextraction method (HS-SDME) for determination of sulfite in the form of sulfur dioxide was developed. An optical probe was used as the droplet holder in the HS-SDME procedure, and the analytical signal (absorbance) was monitored online during the extraction process. The method is based on the conversion of sulfite to volatile sulfur dioxide by acidification of the analyzed solution. The liberated SO2 was absorbed by 25 MUL of an aqueous mixed reagent solution placed on the optical probe tip and containing Fe(III), 1,10-phenantroline, and an acetic buffer solution of pH 5.6. During the extraction process, Fe(III) reduces to Fe(II) and the Fe(II) formed then reacts with 1,10-phenantroline to form a colored complex. Absorbance was measured at 510 nm. The calibration plot was linear in the range 0.032-0.320 mg L-1 of sulfite (as SO2), with a correlation coefficient of 0.9989. The limit of detection (LOD), calculated as three times the standard deviation of the blank test (n = 10), was found to be 8 MUg L-1. The method was applied for analysis of real food samples, such as wine, jam, and juice. PMID- 27669897 TI - Shortcuts to adiabaticity by counterdiabatic driving for trapped-ion displacement in phase space. AB - The application of adiabatic protocols in quantum technologies is severely limited by environmental sources of noise and decoherence. Shortcuts to adiabaticity by counterdiabatic driving constitute a powerful alternative that speed up time-evolution while mimicking adiabatic dynamics. Here we report the experimental implementation of counterdiabatic driving in a continuous variable system, a shortcut to the adiabatic transport of a trapped ion in phase space. The resulting dynamics is equivalent to a 'fast-motion video' of the adiabatic trajectory. The robustness of this protocol is shown to surpass that of competing schemes based on classical local controls and Fourier optimization methods. Our results demonstrate that shortcuts to adiabaticity provide a robust speedup of quantum protocols of wide applicability in quantum technologies. PMID- 27669898 TI - Heat production and error probability relation in Landauer reset at effective temperature. AB - The erasure of a classical bit of information is a dissipative process. The minimum heat produced during this operation has been theorized by Rolf Landauer in 1961 to be equal to kBT ln2 and takes the name of Landauer limit, Landauer reset or Landauer principle. Despite its fundamental importance, the Landauer limit remained untested experimentally for more than fifty years until recently when it has been tested using colloidal particles and magnetic dots. Experimental measurements on different devices, like micro-mechanical systems or nano electronic devices are still missing. Here we show the results obtained in performing the Landauer reset operation in a micro-mechanical system, operated at an effective temperature. The measured heat exchange is in accordance with the theory reaching values close to the expected limit. The data obtained for the heat production is then correlated to the probability of error in accomplishing the reset operation. PMID- 27669899 TI - Developing an antibacterial super-hydrophilic barrier between bacteria and membranes to mitigate the severe impacts of biofouling. AB - Biofouling produces concentrated microbial populations with highly resistive biofilms and is considered to be a serious obstacle for a wide range of membrane technology applications. An antibacterial super-hydrophilic barrier could help to reduce biofouling by preventing direct contact between membranes and bacteria. In this study, an antibacterial super-hydrophilic barrier consisting of a layer of TiO2 nanoparticles (NPs) was developed on polyvinylidene fluoride (PVDF)-based membrane via a facile technique. The results demonstrated that the presence of TiO2 NPs eliminated the first step of biofouling, ie bacterial adhesion to the membrane. In addition, after bacterial deposition onto the membrane during ultrafiltration (UF), the TiO2 NPs significantly retarded bacterial growth and reproduction (the second step of biofouling). During UF, the membrane flux decreased due to bacterial deposition, but 85% of the flux was recovered through physical cleaning using water. This study sheds light on the potential advantages of antibacterial super-hydrophilic membranes for biofouling mitigation. PMID- 27669900 TI - Biofilm forming potential and antimicrobial susceptibility of newly emerged Western Australian Bordetella pertussis clinical isolates. AB - Whooping cough caused by Bordetella pertussis is increasing in several countries despite high vaccine coverage. One potential reason for the resurgence is the emergence of genetic variants of the bacterium. Biofilm formation has recently been associated with the pathogenesis of B. pertussis. Biofilm formation of 21 Western Australian B. pertussis clinical isolates was investigated. All isolates formed thicker biofilms than the reference vaccine strain Tohama I while retaining susceptibility to ampicillin, erythromycin, azithromycin and streptomycin. When two biofilm-forming clinical isolates were compared with Tohama I, minimum bactericidal concentrations of antimicrobial agents increased. Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis revealed significant differences in protein expression in B. pertussis biofilms, providing an opportunity for identification of novel biofilm-associated antigens for incorporation in current pertussis vaccines to improve their protective efficacy. The study also highlights the importance of determining antibiograms for biofilms to formulate improved antimicrobial therapeutic regimens. PMID- 27669901 TI - Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca2+/H+ antiporter. AB - Leucine zipper-EF-hand-containing transmembrane protein1 (LETM1) is located in the mitochondrial inner membrane and is defective in Wolf-Hirschhorn syndrome. LETM1 contains only one transmembrane helix, but it behaves as a putative transporter. Our data shows that LETM1 knockdown or overexpression robustly increases or decreases mitochondrial Ca2+ level in HeLa cells, respectively. Also the residue Glu221 of mouse LETM1 is identified to be necessary for Ca2+ flux. The mutation of Glu221 to glutamine abolishes the Ca2+-transport activity of LETM1 in cells. Furthermore, the purified LETM1 exhibits Ca2+/H+ anti-transport activity, and the activity is enhanced as the proton gradient is increased. More importantly, electron microscopy studies reveal a hexameric LETM1 with a central cavity, and also, observe two different conformational states under alkaline and acidic conditions, respectively. Our results indicate that LETM1 is a Ca2+/H+ antiporter and most likely responsible for mitochondrial Ca2+ output. PMID- 27669903 TI - The Evolution of Hyperedge Cardinalities and Bose-Einstein Condensation in Hypernetworks. AB - To depict the complex relationship among nodes and the evolving process of a complex system, a Bose-Einstein hypernetwork is proposed in this paper. Based on two basic evolutionary mechanisms, growth and preference jumping, the distribution of hyperedge cardinalities is studied. The Poisson process theory is used to describe the arrival process of new node batches. And, by using the Poisson process theory and a continuity technique, the hypernetwork is analyzed and the characteristic equation of hyperedge cardinalities is obtained. Additionally, an analytical expression for the stationary average hyperedge cardinality distribution is derived by employing the characteristic equation, from which Bose-Einstein condensation in the hypernetwork is obtained. The theoretical analyses in this paper agree with the conducted numerical simulations. This is the first study on the hyperedge cardinality in hypernetworks, where Bose-Einstein condensation can be regarded as a special case of hypernetworks. Moreover, a condensation degree is also discussed with which Bose-Einstein condensation can be classified. PMID- 27669902 TI - Gene expression profiling reveals aryl hydrocarbon receptor as a possible target for photobiomodulation when using blue light. AB - Photobiomodulation (PBM) with blue light induces a biphasic dose response curve in proliferation of immortalized human keratinocytes (HaCaT), with a maximum anti proliferative effect reached with 30min (41.4 J/cm2). The aim of this study was to test the photobiomodulatory effect of 41.4 J/cm2 blue light irradiation on ROS production, apoptosis and gene expression at different time points after irradiation of HaCaT cells in vitro and assess its safety. ROS concentration was increased 30 min after irradiation. However, already 1 h after irradiation, cells were able to reduce ROS and balance the concentration to a normal level. The sudden increase in ROS did not damage the cells, which was demonstrated with FACS analysis where HaCaT cells did not show any sign of apoptosis after blue light irradiation. Furthermore, a time course could be seen in gene expression analysis after blue light, with an early response of stimulated genes already 1 h after blue light irradiation, leading to the discovery of the aryl hydrocarbon receptor as possible target for blue light irradiation. PMID- 27669904 TI - Identification and molecular characterization of bacteriophage phiAxp-2 of Achromobacter xylosoxidans. AB - A novel Achromobacter xylosoxidans bacteriophage, phiAxp-2, was isolated from hospital sewage in China. The phage was morphologically and microbiologically characterized, and its one-step growth curve, host range, genomic sequence, and receptor were determined. Its morphology showed that phiAxp-2 belongs to the family Siphoviridae. Microbiological characterization demonstrated that pH 7 is most suitable for phage phiAxp-2; its titer decreased when the temperature exceeded 50 degrees C; phiAxp-2 is sensitive to ethanol and isopropanol; and the presence of calcium and magnesium ions is necessary to accelerate cell lysis and improve the formation of phiAxp-2 plaques. Genomic sequencing and a bioinformatic analysis showed that phage phiAxp-2 is a novel bacteriophage, consisting of a circular, double-stranded 62,220-bp DNA molecule with a GC content of 60.11% that encodes 86 putative open reading frames (ORFs). The lipopolysaccharide of A. xylosoxidans is involved in the adsorption of phiAxp-2. PMID- 27669906 TI - "The beneficiaries of development funding have more often been the managerial elite rather than front-line nurses". AB - The effects of the internal market on the health service have been under constant scrutiny. But the market's impact on nurse education, while largely hidden, has been as dramatic if not as emotive. For colleges of nursing, the transition into the commercial world has been quick and painful. Many believe that the market poses a real threat to the future of the profession. Intake figures have dropped alarmingly, not because of any thorough examination of future supply needs, but through crude and inaccurate estimations by education commissioners. PMID- 27669905 TI - Development and user validation of driving tasks for a power wheelchair simulator. AB - : Mobility is important for participation in daily activities and a power wheelchair (PW) can improve quality of life of individuals with mobility impairments. A virtual reality simulator may be helpful in complementing PW skills training, which is generally seen as insufficient by both clinicians and PW users. To this end, specific, ecologically valid activities, such as entering an elevator and navigating through a shopping mall crowd, have been added to the McGill wheelchair (miWe) simulator through a user-centred approach. PURPOSE: The objective of this study was to validate the choice of simulated activities in a group of newly trained PW users. METHODS: We recruited 17 new PW users, who practiced with the miWe simulator at home for two weeks. They then related their experience through the Short Feedback Questionnaire, the perceived Ease of Use Questionnaire, and semi-structured interviews. RESULTS: Participants in general greatly appreciated their experience with the simulator. During the interviews, this group made similar comments about the activities as our previous group of expert PW users had done. They also insisted on the importance of realism in the miWe activities, for their use in training. DISCUSSION: A PW simulator may be helpful if it supports the practice of activities in specific contexts (such as a bathroom or supermarket), to complement the basic skills training received in the clinic (such as driving forward, backward, turning, and avoiding obstacles). Implications for Rehabilitation New power wheelchair users appreciate practicing on a virtual reality simulator and find the experience useful when the simulated diving activities are realistic and ecologically valid. User-centred development can lead to simulated power wheelchair activities that adequately capture everyday driving challenges experienced in various environmental contexts. PMID- 27669907 TI - ? AB - Home at last: Stacey Gilmore who spent the first 16 months of her life hi the care of staff at Birmingham City Hospital, Dudley Road, has finally gone home. Stacey was born 14 weeks premature and weighing only 875gms (lib 13oz). She went home briefly last year but had to return because of a lung infection. Senior midwife Margaret Clarke, right, said: 'It is marvellous to see Stacey in such good health. She suffered more illnesses in the first year of life than most of us do in a lifetime.' Also pictured are staff nurse Gwen Jackson, left, and Stacey's mother Sharon Brinton. PMID- 27669908 TI - DoH plans for nurse education welcomed. AB - A major Department of Health strategy document on the future of nurse education in England has been warmly welcomed by the profession. PMID- 27669909 TI - Reforms announced for special hospitals. AB - Radical reforms proposed for the UK's top security hospitals are in danger of foundering unless nurses move quickly to promote the 'golden opportunity' they represent, a leading nurse has warned. PMID- 27669910 TI - Job scheme gets funding into 1996. AB - A scheme to help newly-qualified nurses find jobs by offering work experience is set to continue into 1996, Nursing Standard was told last week. PMID- 27669911 TI - Praise for breast care nurses. AB - Breast care nurses have been 'vital' in helping the NHS Breast Screening Programme exceed screening targets in England and Wales for the third year running, the RCN said last week. PMID- 27669912 TI - Nurses face new PRP scheme based on trust performance. AB - A row has erupted over attempts by a Northern trust to impose a new performance related pay scheme which the RCN has warned is open to 'management bias and unfairness'. PMID- 27669914 TI - Midwives to call for extra security. AB - An emergency motion at the Royal College of Midwives' Annual Conference this week will call for tighter security in maternity units. PMID- 27669913 TI - Nurse records can be 'vital' in court. AB - Nursing records are often crucial in establishing the facts when a medical negligence claim comes to trial, Susan Parker, a nurse adviser with the Medical Defence Union claimed this week. PMID- 27669916 TI - Nursing staff in limbo as two military hospitals face closure. AB - Severe cuts in the number of nurses working in the Defence Medical Service are expected as a result of the defence savings announced by the Government last week. PMID- 27669915 TI - ? PMID- 27669917 TI - UKCC leaders silent as grievance begins. AB - A stony silence continued to envelop the leadership of the UK Central Council as angered staff began official grievance procedures, demanding that ethical questions over the appointment of an administrative manager be addressed. PMID- 27669918 TI - RCN alert before axe attack. AB - A Royal College of Nursing officer wrote to a south Wales hospital about security concerns just a week before a man armed with an axe injured six people including three nurses and a policeman. PMID- 27669919 TI - RCN attacks health service for failing to invest in its staff. AB - The health service's failure to invest in its staff is its biggest failing, RCN Director of Education Tom Bolger told the conference. PMID- 27669920 TI - Nurses set for roles as chief executives. AB - Nurses will soon be trust chief executives as the NHS realises their general management potential, outspoken health commentator Professor Eric Caines predicted last week. PMID- 27669921 TI - Rowden: patients should be told of surgeons' death rates. AB - Nurses have more valuable information to share with the public, such as under which surgeons patients arc most likely to die, than has been offered in the new hospital league tables, Ray Rowden, Institute of Health Services Management director claimed last week. PMID- 27669922 TI - CHCs' concern over confidentiality. AB - Community health councils called for a new 'whistleblowers' charter' to allow NHS staff to raise concerns about services and patient care wthout risking disciplinary action. PMID- 27669923 TI - Cuts spark no confidence vote. AB - Furious nursing staff at a struggling trust hospital have taken a vote of no confidence in the trust managers after an announcement of sweeping redundancies. PMID- 27669926 TI - Guidelines on child abuse from the HVA. AB - Health visitors and school nurses have been urged to lead the fight against the rising incidence of child abuse. PMID- 27669924 TI - Nurses must ensure health resources are properly targeted. AB - Health visitors and public health nurses must battle to ensure resources are being targeted at the people who most need them, a senior nurse in public health has urged. PMID- 27669927 TI - Whitehall ditches nurse transfers. AB - Plans for transferring thousands of nurses from the NHS to local authority employment have been ditched by the Government. PMID- 27669928 TI - Male rape law. AB - A new offence of male rape with a maximum penalty of life imprisonment is to be introduced in England and Wales. PMID- 27669929 TI - Blunkett welcome for joint ventures. AB - Shadow Health Secretary David Blunkett has lamented his party's failure to embrace joint commissioning with local authorities early enough. PMID- 27669931 TI - Disaster procedure success for south african nurses during pre-election riots. AB - South African nurses have hailed the success of a disaster plan which was put into full effect during recent riots in Johannesburg. PMID- 27669932 TI - Child health staff accused of not keeping up with research. AB - Workers in child health services have been criticised for failure to keep abreast of the latest research. PMID- 27669933 TI - Nurses must act on DoH report. AB - Mental health nurses will be doomed to a fossilised existence' if they fail to focus services on patient need, John Tait, Deputy Chief Nursing Officer at the health department, told the conference. PMID- 27669934 TI - ? AB - The executive committee of the Northern Ireland Royal College of Nursing Society of Mental Health Nursing held its first meeting in Belfast last month. Pictured, back left to right, are: Hugo Kelly, senior staff nurse at St Luke's Hospital; John Hall, charge nurse at Tyrone Manor Hospital; and Tom Sandford, RCN Mental Health Adviser: and front, left to right: Arleen Hill, staff nurse; Teresa Kelly, staff nurse at St Luke's Hospital; Eileen Scott, RCN Northern Ireland Board officer; Rosalee Corvan, Society secretary; and Ester McKee, community psychiatric nurse, Dunlace Health Centre. PMID- 27669935 TI - Mental health services heading for crisis. AB - Mental health services in many parts of the UK are 'dangerously close to crisis point', RCN mental health nursing adviser Tom Sandford claimed last week. PMID- 27669937 TI - Calls for replacing project 2000 are misplaced. AB - Calls for generic all-graduate nurse training to replace Project 2000 are rooted in the vanity of the profession rather than in a desire to meet patient need, the conference was told. PMID- 27669938 TI - Wide variation in immunity to hepatitis B found in midwives. AB - The immunity of nurses and midwives to hepatitis B varies enormously across the country, despite government guidelines that all staff involved in exposure-prone procedures should be immune to the virus by next year. PMID- 27669939 TI - We must all drink 1.1 litres a day. PMID- 27669940 TI - Caesarean births soar in britain. AB - The number of Caesarean births carried out in Britain has jumped dramatically over the past year, according to latest figures. Both doctors and midwives blame the growing fear of litigation as the cause for the rise. PMID- 27669941 TI - New TB screening for developing countries. AB - A new method for preparing smears to detect tuberculosis which is appropriate for developing countries has been devised by researchers in Ethiopia. PMID- 27669942 TI - Improved breast cancer survival in all age groups. AB - Both short and long term survival of women with breast cancer has improved considerably in all age groups, results of a study from The Netherlands suggests. PMID- 27669944 TI - Warning of iritis after streptokinase. AB - Severe bilateral iritis might be a delayed allergic reaction to intravenous streptokinase injection, doctors from South Glamorgan report. PMID- 27669943 TI - Flooring developed to be more 'faller-friendly'. AB - A floor covering which might protect older people from fractured bones if they fall has been devised by American researchers. PMID- 27669945 TI - Women doing it for themselves. AB - A Leicester nurse, concerned by the amount of mental health problems on a city housing estate, has finally achieved her ambition to set up a self-help group for stressed and depressed women. PMID- 27669946 TI - Oppressed cannot lead healthy lives. AB - The government is trying to criminalise 'aggravated' trespass and many forms of protest. It also wants to repeal the 1968 Caravans Act, which obliges councils to provide sites for gypsy families, to abolish the right to remain silent when arrested, to give the police new powers to arrest those who they think might be ravers, protestors or travellers (including gypsies) and the power to form exclusion zones, thus limiting totally the rights to freedom of movement and of association. PMID- 27669947 TI - A case for cannabis in the relief of pain. AB - I was pleased to see in your News section that at hist some MPs are taking up the case in favour of legalising cannabis prescribing for the relief of pain in multiple sclerosis (Move to legalise cannabis for multiple sclerosis sufferers, June 29). PMID- 27669948 TI - Let's have a balanced view of nursing homes. AB - How sad it makes me to read so much about the poor standard of our nursing homes. PMID- 27669949 TI - Twelve-hour shifts are not the answer. AB - In Linda Nazarko's article, 'Short shrift for long shifts' (Viewpoint, June 29), she puts forward the case against 12-hour shifts in her usual articulate way. PMID- 27669950 TI - NHS 'company cars' not seen as a perk. AB - Regarding your news item headed 'Unfair tax trap system penalises community nurses' (June 29). This spiralling cost does not only apply to the cost of lease car schemes. The users of Crown and fleet cars provided by the health authorities are also penalised by this unfair tax treatment. PMID- 27669952 TI - Elizabeth mary 'emily' hughes. AB - Emily Hughes, a founder member of the Gwynedd Branch of the Royal College of Nursing died last month at the age of 91. PMID- 27669951 TI - Taking the risk out of risk assessment. AB - Risk assessment is indeed a tried and tested management tool in industry that is new to the health service. Mary Spinks' article indicates that it is new to her, too (Patient safety, risky business, Features,June 29). PMID- 27669953 TI - Victorian values and mental health nursing. AB - It was disappointing to read the article on mental health nursing featured in the Appointments section because it gave no indication of the positive side of those large psychiatric institutions (Mental health nursing, June 29). PMID- 27669955 TI - Integrating Social Support in Nursing Integrating Social Support in Nursing M. j . Stewart SAGE 246pp L12.95 0-8039-4274-5. AB - The first thing which one notices about Integrating Social Support in Nursing is that it is a Canadian publication with American- English spelling and terminology throughout. Early examples are: 'operationalization of the construct and hypothesis' and 'explicates the critical bidirectional nature'. These are not isolated examples, and similar wording permeates the whole book. PMID- 27669954 TI - Information exchange. AB - I am a staff nurse researching the best format for a 24 hour admission sheet for day case patients admitted to our ward which usually accommodates longer stay patients. These patients generally include emergencies and day case surgery. PMID- 27669956 TI - Developing a Philosophy of Nursing Developing a Philosophy of Nursing J Kikuchi H Simmons SAGE 126pp L13.95 0-8039-5423-9 [Formula: see text]. AB - Developing a Philosophy of Nursing is a collection of essays based on papers presented at a 1991 conference at the Institute for Philosophical Nursing Research in Canada. The aim was to air and explore opposing arguments about how a sound philosophy of nursing should be developed. PMID- 27669957 TI - Taking drugs seriously Taking drugs seriously J Cohen J Kay Thorsons 174pp L4.99 0-7225-2858-2. AB - In 1979, when I began giving talks about drugs and my experiences as a social worker in London's East End, alcohol and nicotine were the only substances which were featured. Recently, however, my talks have included heroin and other similarly 'heavy' drugs. PMID- 27669958 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road. Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27669959 TI - Peripheral calcifying cystic odontogenic tumour and peripheral dentinogenic ghost cell tumour: an updated systematic review of 117 cases reported in the literature. AB - PURPOSE: To integrate the available data published on peripheral calcifying cystic odontogenic tumour (CCOT) and peripheral dentinogenic ghost cell tumour (DGCT) into a comprehensive analysis of its clinical and radiologic features. METHODS: An electronic search was undertaken in May, 2016. Eligibility criteria included publications reporting cases of peripheral CCOTs/DGCTs having enough clinical, radiological and histological information to confirm a definite diagnosis. Demographic data, lesion site and size, treatment approach and recurrence were analyzed. RESULTS: Hundred and thirty-eight lesions were found (65 publications), and 117 lesions (63 publications) with enough information were analyzed (55 CCOTs, 50 DGCTs, 12 unknown). Mean age of patients was 51.3 +/- 23.4 (min-max, 1-92), with higher mean age for the DGCTs variant. The lesions were more prevalent in the mandible, anterior region of the jaws, and in the second, sixth and eighth decades, with an equal sexual distribution. About 20% of all lesions showed signs of erosion of the underlying bone, with a higher rate for DGCTs. The mean lesion size was 1.3 +/- 0.8 (min-max, 0.4-3.0). Time of follow-up was informed for 37 lesions, with a mean +/- SD of 30.2 +/- 21.0 months (min-max, 6-84). Almost all lesions were treated by conservative surgery; only three recurrences were reported. CONCLUSIONS: Peripheral CCOTs/DGCTs are rare lesions. Most of the lesions were treated by simple excision with or without curettage of the underlying bone. As the recurrence rate is very low, a conservative approach seems to be enough for the great majority of cases. PMID- 27669960 TI - Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells. AB - Distinct subtypes of ionotropic glutamate receptors can segregate to specific synaptic inputs in a given neuron. Using functional mapping by focal glutamate uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs) are strictly confined to the postsynaptic elements of mossy fibre (mf) synapses and excluded from other glutamatergic inputs and from extrasynaptic compartments. By molecular replacement in organotypic slices from GluK2 knockout mice, we show that the faithful rescue of KAR segregation at mf-CA3 synapses critically depends on the amount of GluK2a cDNA transfected and on a sequence in the GluK2a C terminal domain responsible for interaction with N-cadherin. Targeted deletion of N-cadherin in CA3 PCs greatly reduces KAR content in thorny excrescences and KAR EPSCs at mf-CA3 synapses. Hence, multiple mechanisms combine to confine KARs at mf-CA3 synapses, including a stringent control of the amount of GluK2 subunit in CA3 PCs and the recruitment/stabilization of KARs by N-cadherins. PMID- 27669961 TI - Clinical photoacoustic imaging of cancer. AB - Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented. PMID- 27669963 TI - Specific Aspects of Drug Hypersensitivity in Children. AB - Suspicion for drug hypersensitivity (DH) is a common reason for children's referral to an allergy department, with beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) as the most frequently involved drugs. The prevalence of DH in children remains not well defined as epidemiologic studies in children are lacking, and the most of those take into account adverse drug reactions (ADR) without a systematic allergy work-up to confirm or exclude hypersensitivity. The clinical history is mandatory in order to classify the reaction as being immediate or non-immediate and then to subsequently adapt the allergy work-up. Mainly due to the lack of studies, the same guidelines used for diagnosis of drug allergy in adults are generally used in the pediatric population, and the diagnosis is based mainly on in vivo tests (i.e. skin tests and/or drug provocation test) and rarely on in vitro tests. However, specific aspects of management of DH in children have been recently highlighted. PMID- 27669964 TI - Predictive Modeling of Ocular Pharmacokinetics and Adverse Effects. AB - Treatment of ocular disorders is a challenge due to the difficulty of delivering drugs to the target tissues within the eye at sufficient concentrations to produce a therapeutic effect. The cornea and the blood-retinal barrier, comprising of the retinal pigment epithelium and the retinal capillaries, are the main barriers for delivering drugs to treat diseases in the anterior and posterior parts of the eye, respectively. The eye has a rich blood supply and relatively small mass, and drugs can distribute from the systemic blood circulation to the choroid through the fenestrated choroidal blood vessels, but further permeation into the eye is limited by the blood-retinal barrier. Computational prediction of the ocular pharmacokinetics of drugs can help improve drug delivery and predict ocular adverse effects resulting from ocular or systemic drugs. Computational models predicting ocular adverse effects of drugs are still scarce, even though prediction of eye irritation and corrosion of chemicals has been well studied as a consequence of recent European Union legislation. Predictive modeling of adverse effects suffers from the wide distribution of data resources, but databases that integrate data on adverse effects, drugs, targets and other related biological data from different sources offer improved prospects for predictive modeling. PMID- 27669962 TI - Diagnostic vascular ultrasonography with the help of color Doppler and contrast enhanced ultrasonography. AB - The use of ultrasonography and especially of contrast-enhanced ultrasonography (CEUS) in the diagnosis of vascular pathologies before and after interventions has significantly increased over the past years due to the broader availability of modern ultrasound systems with CEUS capabilities and more trained user experience in this imaging modality. For the preinterventional and postinterventional work-up of carotid diseases, duplex ultrasound as well as CEUS have been established as the standard-of-care examination procedures for diagnosis, evaluation, and follow-up. In addition to its use for carotid arterial diseases, ultrasonography has also become the primary modality for the screening of vascular pathologies. This review describes the most common pathologies found in ultrasonography of the carotid arteries, the abdominal aorta, and the femoral arteries. PMID- 27669966 TI - Identification of Useful Nanobodies by Phage Display of Immune Single Domain Libraries Derived from Camelid Heavy Chain Antibodies. AB - BACKGROUND: The discovery of functional heavy chain-only antibodies devoid of light chains in sera of camelids and sharks in the early nineties provided access to the generation of minimal-sized, single-domain, in vivo affinity-matured, recombinant antigenbinding fragments, also known as Nanobodies. METHODS: Recombinant DNA technology and adaptation of phage display vectors form the basis to construct large naive, synthetic or medium sized immune libraries from where multiple Nanobodies have been retrieved. Alternative selection methods (i.e. bacterial display, bacterial two-hybrid, Cis-display and ribosome display) have also been developed to identify Nanobodies. The antigen affinity, stability, expression yields and structural details of the Nanobodies have been determined by standard technology. Nanobodies were subsequently engineered for higher stability and affinity, to have a sequence closer to that of human immunoglobulin domains, or to add designed effector functions. RESULTS: Antigen specific Nanobodies recognizing with high affinity their cognate antigen were retrieved from various libraries. High expression yields are obtained from microorganisms, even when expressed in the cytoplasm. The purified Nanobodies are shown to possess beneficial biochemical and biophysical properties. The crystal structure of Nanobody::antigen complexes reveal the preference of Nanobodies for cavities on the antigen surface. CONCLUSION: Thanks to the properties described above, Nanobodies became a highly valued and versatile tool for biomolecular research. Moreover, numerous diagnostic and therapeutic Nanobody-based applications have been developed in the past decade. PMID- 27669967 TI - Therapeutic Antibodies by Phage Display. AB - BACKGROUND: Antibody phage display is a major technological platform for the generation of fully human antibodies for therapeutic purposes. The in vitro binder selection by phage display allows researchers to have more extensive control over binding parameters and facilitates the isolation of clinical candidate antibodies with desired binding and/or functional profiles. METHODS: Since the invention of antibody phage display in late 1980s, significant technological advancements in the design, construction, and selection of the antibody libraries have been made, and several fully human antibodies generated by phage display are currently approved or in various clinical development stages. RESULTS: In this review, the background and details of antibody phage display technology, and representative antibody libraries with natural or synthetic sequence diversity and different construction strategies are described. The generation, optimization, functional and biophysical properties, and preclinical and clinical developments of some of the phage display-derived therapeutic antibodies approved for use in patients or in late-stage clinical trials are also discussed. CONCLUSION: With evolving novel disease targets and therapeutic strategies, antibody phage display is expected to continue to play a central role in the development of the next generation of therapeutic antibodies. PMID- 27669965 TI - Polypharmacology in Precision Oncology: Current Applications and Future Prospects. AB - Over the past decade, a more comprehensive, large-scale approach to studying cancer genetics and biology has revealed the challenges of tumor heterogeneity, adaption, evolution and drug resistance, while systems-based pharmacology and chemical biology strategies have uncovered a much more complex interaction between drugs and the human proteome than was previously anticipated. In this mini-review we assess the progress and potential of drug polypharmacology in biomarker-driven precision oncology. Polypharmacology not only provides great opportunities for drug repurposing to exploit off-target effects in a new single target indication but through simultaneous blockade of multiple targets or pathways offers exciting opportunities to slow, overcome or even prevent inherent or adaptive drug resistance. We highlight the many challenges associated with exploiting known or desired polypharmacology in drug design and development, and assess computational and experimental methods to uncover unknown polypharmacology. A comprehensive understanding of the intricate links between polypharmacology, efficacy and safety is urgently needed if we are to tackle the enduring challenge of cancer drug resistance and to fully exploit polypharmacology for the ultimate benefit of cancer patients. PMID- 27669968 TI - Unraveling Antibody Display: Systems Biology and Personalized Medicine. AB - BACKGROUND: The identification of combinatorial antibodies against many different targets in oncology, autoimmune, inflammatory and infectious diseases has uncovered novel strategies to control and prevent diseases' onset and progression, and represents the fastest growing market for the pharmaceutical industry. Phage Display has been successfully used in the identification of unknown targets, which combines shotgun approaches with high throughput selection schemes. METHODS: This specific review covers many aspects of combinatorial phage display technology starting from antibody selection strategies to its redesign for application purposes. Emphasis is specifically directed to how these biotherapeutics function on specific targets with an interactome view, especially within complex diseases. CONCLUSION: Novel combinatorial antibodies will lead to improved interventions in cancer, autoimmune and infectious diseases; however, the very large genetic diversity associated with environmental variations highlight the importance of the personalized medicine using a system's biology approach. Therefore, combined therapies are expected in the near future. PMID- 27669969 TI - Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery. AB - BACKGROUND: Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naive, immune and synthetic libraries. METHODS: Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. RESULTS: This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. CONCLUSION: We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. PMID- 27669970 TI - Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes. AB - The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment responsivity and adherence; altered glycemic control and increased risk of wider medical complications. A number of factors link MDD to metabolic associated disorders, including: higher rates of shared risk factors such as poor diet and physical inactivity and biological elements including increased inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction. All of these biological factors have been extensively investigated in the pathophysiology of obesity and type 2 diabetes mellitus as well as MDD. In this review, we aim to: (1) overview the epidemiological links between MDD, obesity and type 2 diabetes mellitus; (2) discuss the role of synergistic neurotoxic effects in MDD comorbid with obesity, and type 2 diabetes mellitus; (3) review evidence of intestinal dysbiosis, leaky gut and increased bacterial translocation, in the pathophysiology of MDD, obesity and type 2 diabetes mellitus; and (4) propose a model in which the gut-brain axis could play a pivotal role in the comorbidity of these disorders. PMID- 27669971 TI - A randomised, single-blind comparison of high-level disinfectants for flexible nasendoscopes. AB - OBJECTIVES: To compare the microbiological efficacy, turnaround time, cost, convenience, and patient and user tolerance of Tristel Trio Wipes, PeraSafe solution and Cidex OPA solution for the high-level disinfection of flexible nasendoscopes. METHODS: Flexible nasendoscopes were used in routine clinical encounters. They were then disinfected with one of the three disinfectant methods. Surveillance cultures were taken before and after each disinfection process. Data relating to each of the study parameters were recorded. RESULTS: Positive bacterial cultures were discovered on nasendoscopes disinfected with PeraSafe and Cidex OPA. Tristel Trio Wipes have no capital outlay cost, the lowest running cost, the greatest convenience and the fastest turnaround time. PeraSafe had a faster turnaround time than Cidex OPA, and lower running costs. CONCLUSION: Tristel Trio Wipes are equal to PeraSafe and Cidex OPA in terms of microbiological efficacy. Turnaround time and cost are dramatically reduced when using Tristel Trio Wipes compared to the other disinfectant methods. PMID- 27669972 TI - Long-range antiferromagnetic order and possible field induced spin-flop transition in BiMnVO5. AB - We report the bulk magnetic characterization of a dimeric chain material, BiMnVO5, by means of magnetic susceptibility, magnetization and heat capacity measurements. Our results provide compelling evidence of an antiferromagnetic (AFM) transition at (T N) ~ 11.5 K. Moreover, the magnetic entropy change in zero field saturates to 14.6 J mol-1 K-1 which is close to the total spin entropy of Mn2+. The development of long-range magnetic order in this chain material demonstrates the interplay of strong intra-chain and inter-chain interactions between the dimers, in addition to the intra-dimer interaction. Low-temperature (T < T N) heat capacity data indicate the presence of a gap (Delta/k B ~ 5 K) in the spin excitations. Furthermore, the isothermal magnetization below T N shows an anomaly in the slope between 30 and 40 kOe which is suggestive of a spin flop transition. Such a low-field spin-flop transition and gapped spin wave excitations may be attributed to the presence of (weak) magnetic anisotropy in this material. We attempt to construct a phase diagram in the magnetic field temperature plane by extracting data from in-field heat capacity and isothermal magnetization measurements. PMID- 27669973 TI - C-X-C motif chemokine 10 in non-alcoholic steatohepatitis: role as a pro inflammatory factor and clinical implication. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD and causes subsequent pathological changes including cirrhosis and hepatocellular carcinoma. Inflammation is the key pathological change in NASH and involves a series of cytokines and chemokines. The C-X-C motif chemokine 10 (CXCL10), which is known as a pro-inflammation chemokine, was recently proven to play a pivotal role in the pathogenesis of NASH. Hepatic CXCL10 is mainly secreted by hepatocytes and liver sinusoidal endothelium. By binding to its specific receptor CXCR3, CXCL10 recruits activated CXCR3+ T lymphocytes and macrophages to parenchyma and promotes inflammation, apoptosis and fibrosis. The circulating CXCL10 level correlates with the severity of lobular inflammation and is an independent risk factor for NASH patients. Thus, CXCL10 may be both a potential prognostic tool and a therapeutic target for the treatment of patients with NASH. The aim of this review is to highlight the growing advances in basic knowledge and clinical interest of CXCL10 in NASH to propagate new insights into novel pharmacotherapeutic avenues. PMID- 27669974 TI - Graphdiyne as a High-Efficiency Membrane for Separating Oxygen from Harmful Gases: A First-Principles Study. AB - We theoretically explored the adsorption and diffusion properties of oxygen and several harmful gases penetrating the graphdiyne monolayer. According to our first-principles calculations, the oxidation of the acetylenic bond in graphdiyne needs to surmount an energy barrier of ca. 1.97 eV, implying that graphdiyne remains unaffected under oxygen-rich conditions. In a broad temperature range, graphdiyne with well-defined nanosized pores exhibits a perfect performance for oxygen separation from typical noxious gases, which should be of great potential in medical treatment and industry. PMID- 27669975 TI - Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis. AB - Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID- 27669977 TI - Paper-Based, Hand-Drawn Free Chlorine Sensor with Poly(3,4 ethylenedioxythiophene):Poly(styrenesulfonate). AB - The concentration of free chlorine used for disinfecting drinking water, recreational water, and food processing water is critical for environmental and human health conditions, and should be controlled within stipulated ranges. This report, for the first time, describes a paper-based electrochemical free chlorine sensor fabricated by hand-drawing. The electrical resistivity of a poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) chemoresistor increases when it is exposed to free chlorine in water due to oxidation reactions. Because the relative change of the electrical resistance represents the sensor's response, the sensor can be fabricated by hand-drawing with different shapes and dimensions. The fabrication steps are all at room temperature, require no instrumentation or equipment, and can be carried out by untrained personnel. The fabricated sensor is mechanically stable, reusable, has a wide sensing range, and can accurately measure free chlorine concentrations in real water samples. Therefore, the low-cost, hand-drawn free chlorine sensor is of great significance for water quality monitoring in less developed areas where fabrication facilities, analytical equipment, and trained personnel are limited, but the need for analytical devices is critical. In addition to the free chlorine sensor demonstrated in this study, other types of PEDOT:PSS-based sensors and electronic devices can be fabricated by the developed hand-drawing process. PMID- 27669976 TI - Histological and immunohistochemical characteristics of cerebral amyloid angiopathy in elderly dogs. AB - BACKGROUND: Cerebral amyloid angiopathy (CAA) is a disorder characterized by amyloid deposition in the wall of cerebral blood vessels. The deposits of amyloid occur frequently in the blood vessels of the frontal, parietal and occipital cortex. OBJECTIVE: To examine the characteristics of CAA classified according to the Vonsattel scale in elderly dogs histologically and immunohistochemically as well as the semi-quantitative evaluation of the amyloid deposits in the different segments of the brain. ANIMALS AND METHODS: The brains of 36 dogs of different breeds and sexes, which had been routinely necropsied, were used and divided into two groups: dogs from 1 to 5 and 10 to 18 years old. The tissue sections were stained by hematoxylin-eosin, Congo red and immunohistochemically. RESULTS: Amyloid was accumulated in the wall of cerebral blood vessels in 70% of dogs over the age of 10 years predominantly in the frontal cortex. CAA was demonstrated in elderly dogs as follows: in the frontal cortex (n = 19 or 63%), the parietal cortex (n = 12 or 40%), the hippocampus (40%) and the cerebellum (n = 5 or 17%). The deposits of amyloid in the wall of blood vessels detected by Congo red staining were also Abeta1-14 and Abeta1-42 immunohistochemically positive. Most commonly, the amyloid deposits affected a moderate number of blood vessels. The accumulation of amyloid was immunohistochemically revealed in the blood vessel walls as well as in the senile plaques and neurons. CONCLUSION: The amount of amyloid in the arterial walls increased with age in dogs, whereas the amyloid accumulated in plaques was Congo red negative. PMID- 27669978 TI - Patient's experience with subcutaneous and oral methotrexate for the treatment of rheumatoid arthritis. AB - BACKGROUND: Despite the prominent position of methotrexate (MTX) in Rheumatoid Arthiris (RA) therapeutics, its real-world effectiveness may be influenced by a relative lack of tolerability or other side effects that physicians may not be aware of but that are bothersome to patients. The aim of this study is to identify suboptimal patient experience with MTX and to raise awareness for clinicians to identify opportunities to mitigate bothersome symptoms and side effects and optimize response to MTX. METHODS: We conducted a prospective, cross sectional, online survey among RA patients who were members of Creakyjoints, a large arthritis patient community. Eligible participants must have recently initiated a new biologic, subcutaneous (SQ) MTX, or oral MTX in the last 12 months and were uniquely assigned to one of these 3 groups. Descriptive statistics were used to compare patient-reported side effects and tolerability related to MTX use in the 3 medication groups (SQ MTX, oral MTX, and biologic). RESULTS: A total of 382 (85 %) of 448 eligible patients completed the survey and were grouped as: biologic (n = 218), SQ MTX (n = 49), and oral MTX (n = 115). Demographics were mean standard deviation (SD) age 48 (10) years, 92 % white, 91 % women. Symptoms significantly more prevalent in the SQ and oral MTX groups included diarrhea, fatigue, malaise, and hair loss. Injection related pain was lower with SQ MTX compared to SQ biologics. Out of a total of 8 potential symptoms and side effects examined, higher dose MTX (> = 20 mg/week) was associated with a 2.26 (1.25-4.09) greater likelihood of more side effects referent to < =10 mg/week. CONCLUSION: Results from this real-world RA patient cohort suggest that MTX is accompanied by many patient-reported side effects and tolerability problems that may be under-recognized by physicians. These may impact both treatment satisfaction and medication adherence. PMID- 27669979 TI - Modulation of plant growth in vivo and identification of kinase substrates using an analog-sensitive variant of CYCLIN-DEPENDENT KINASE A;1. AB - BACKGROUND: Modulation of protein activity by phosphorylation through kinases and subsequent de-phosphorylation by phosphatases is one of the most prominent cellular control mechanisms. Thus, identification of kinase substrates is pivotal for the understanding of many - if not all - molecular biological processes. Equally, the possibility to deliberately tune kinase activity is of great value to analyze the biological process controlled by a particular kinase. RESULTS: Here we have applied a chemical genetic approach and generated an analog sensitive version of CDKA;1, the central cell-cycle regulator in Arabidopsis and homolog of the yeast Cdc2/CDC28 kinases. This variant could largely rescue a cdka;1 mutant and is biochemically active, albeit less than the wild type. Applying bulky kinase inhibitors allowed the reduction of kinase activity in an organismic context in vivo and the modulation of plant growth. To isolate CDK substrates, we have adopted a two-dimensional differential gel electrophoresis strategy, and searched for proteins that showed mobility changes in fluorescently labeled extracts from plants expressing the analog-sensitive version of CDKA;1 with and without adding a bulky ATP variant. A pilot set of five proteins involved in a range of different processes could be confirmed in independent kinase assays to be phosphorylated by CDKA;1 approving the applicability of the here-developed method to identify substrates. CONCLUSION: The here presented generation of an analog-sensitive CDKA;1 version is functional and represent a novel tool to modulate kinase activity in vivo and identify kinase substrates. Our here performed pilot screen led to the identification of CDK targets that link cell proliferation control to sugar metabolism, proline proteolysis, and glucosinolate production providing a hint how cell proliferation and growth are integrated with plant development and physiology. PMID- 27669981 TI - Erratum to: 'Effectiveness of biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use (VAPrapid-2): study protocol for a randomised controlled trial'. PMID- 27669980 TI - Lack of sleep as a contributor to obesity in adolescents: impacts on eating and activity behaviors. AB - BACKGROUND: Sleep is an important contributor to physical and mental health; however, chronic sleep deprivation has become common in adolescents, especially on weekdays. Adolescents aged 14-17 years are recommended to sleep between 8 and 10 h per night to maximize overall health and well-being. Although sleep needs may vary between individuals, sleep duration recommendations are important for surveillance and help inform policies, interventions, and the population of healthy sleep behaviors. Long sleepers are very rare among teenagers and sleeping too much is not a problem per se; only insufficient sleep is associated with adverse health outcomes in the pediatric population. Causes of insufficient sleep are numerous and chronic sleep deprivation poses a serious threat to the academic success, health and safety of adolescents. This article focuses on the link between insufficient sleep and obesity in adolescents. DISCUSSION: This "call to action" article argues that sleep should be taken more seriously by the public health community and by our society in general, i.e., given as much attention and resources as nutrition and physical activity. Not only that having a good night's sleep is as important as eating a healthy diet and being regularly physically active for overall health, but sleeping habits also impact eating and screen time behaviors and, therefore, can influence body weight control. Short sleep duration, poor sleep quality, and late bedtimes are all associated with excess food intake, poor diet quality, and obesity in adolescents. Sleep, sedentary behavior, physical activity and diet all interact and influence each other to ultimately impact health. A holistic approach to health (i.e., the whole day matters) targeting all of these behaviors synergistically is needed to optimize the impact of our interventions. Sleep is not a waste of time and sleep hygiene is an important factor to consider in the prevention and treatment of obesity. PMID- 27669983 TI - Roger Tsien 1952-2016. PMID- 27669982 TI - TLE3 represses colorectal cancer proliferation by inhibiting MAPK and AKT signaling pathways. AB - BACKGROUND: Transducin-like enhancer of Split3 (TLE3) serves as a transcriptional corepressor during cell differentiation and shows multiple roles in different kinds of cancers. Recently, TLE3 together with many other genes involved in Wnt/beta-catenin pathway were detected hyper-methylated in colorectal cancer (CRC). However, the potential role and the underlying mechanism of TLE3 in CRC progression remain scarce. METHODS: Gene expression profiles were analyzed in The Cancer Genome Atlas (TCGA) microarray dataset of 41 normal colorectal intestine tissues and 465 CRC tissues. Western blot and Real-time Quantitative PCR (RT qPCR) were respectively performed to detect protein and mRNA expression in 8 pairs of CRC tissue and matched adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to evaluate TLE3 protein expression in 105 paraffin-embedded, archived human CRC tissues from patients, whose survival data were analyzed with Kaplan-Meier method. In vitro experiments including MTT assay, colony formation assay, and soft agar formation assay were used to investigate the effects of TLE3 on CRC cell growth and proliferation. Additionally, subcutaneous tumorigenesis assay was performed in nude mice to confirm the effects of TLE3 in vivo. Furthermore, gene set enrichment analysis (GSEA) was run to explore potential mechanism of TLE3 in CRC, and then we measured the distribution of CRC cell cycle phases and apoptosis by flow cytometry, as well as the impacts of TLE3 on MAPK and AKT signaling pathways by Western blot and RT-qPCR. RESULTS: TLE3 was significantly down-regulated in 465 CRC tissues compared with 41 normal tissues. Both protein and mRNA expressions of TLE3 were down-regulated in CRC compared with matched adjacent normal mucosa. Lower expression of TLE3 was significantly associated with poorer survival of patients with CRC. Besides, knock down of TLE3 promoted CRC cell growth and proliferation, while overexpression of TLE3 showed suppressive effects. Furthermore, overexpression of TLE3 caused G1-S phase transition arrest, inhibition of MAPK and AKT pathways, and up-regulation of p21Cip1/WAF1 and p27Kip1. CONCLUSION: This study indicated that TLE3 repressed CRC proliferation partly through inhibition of MAPK and AKT signaling pathways, suggesting the possibility of TLE3 as a biomarker for CRC prognosis. PMID- 27669984 TI - Life and death rest on a bivalent chromatin state. PMID- 27669985 TI - Too bored to stay awake. PMID- 27669986 TI - A useful code for sequences. PMID- 27669987 TI - Dorsal anterior cingulate: a Rorschach test for cognitive neuroscience. PMID- 27669988 TI - Value, search, persistence and model updating in anterior cingulate cortex. AB - Dorsal anterior cingulate cortex (dACC) carries a wealth of value-related information necessary for regulating behavioral flexibility and persistence. It signals error and reward events informing decisions about switching or staying with current behavior. During decision-making, it encodes the average value of exploring alternative choices (search value), even after controlling for response selection difficulty, and during learning, it encodes the degree to which internal models of the environment and current task must be updated. dACC value signals are derived in part from the history of recent reward integrated simultaneously over multiple time scales, thereby enabling comparison of experience over the recent and extended past. Such ACC signals may instigate attentionally demanding and difficult processes such as behavioral change via interactions with prefrontal cortex. However, the signal in dACC that instigates behavioral change need not itself be a conflict or difficulty signal. PMID- 27669989 TI - Dorsal anterior cingulate cortex and the value of control. AB - Debates over the function(s) of dorsal anterior cingulate cortex (dACC) have persisted for decades. So too have demonstrations of the region's association with cognitive control. Researchers have struggled to account for this association and, simultaneously, dACC's involvement in phenomena related to evaluation and motivation. We describe a recent integrative theory that achieves this goal. It proposes that dACC serves to specify the currently optimal allocation of control by determining the overall expected value of control (EVC), thereby licensing the associated cognitive effort. The EVC theory accounts for dACC's sensitivity to a wide array of experimental variables, and their relationship to subsequent control adjustments. Finally, we contrast our theory with a recent theory proposing a primary role for dACC in foraging-like decisions. We describe why the EVC theory offers a more comprehensive and coherent account of dACC function, including dACC's particular involvement in decisions regarding foraging or otherwise altering one's behavior. PMID- 27669992 TI - Predicting changes in mechanical properties of trabecular bone by adaptive remodeling. AB - Because changes in the mechanical properties of bone are closely related to trabecular bone remodeling, methods that consider the temporal morphological changes induced by adaptive remodeling of trabecular bone are needed to estimate long-term fracture risk and bone quality in osteoporosis. We simulated bone remodeling using simplified and pig trabecular bone models and estimated the morphology of healthy and osteoporotic cases. We then displayed the fracture risk of the remodeled models based on a cumulative histogram from high stress. The histogram showed more elements had higher stresses in the osteoporosis model, indicating that the osteoporosis model had a greater risk. PMID- 27669990 TI - Evolving insights into RNA modifications and their functional diversity in the brain. AB - In this Perspective, we expand the notion of temporal regulation of RNA in the brain and propose that the qualitative nature of RNA and its metabolism, together with RNA abundance, are essential for the molecular mechanisms underlying experience-dependent plasticity. We discuss emerging concepts in the newly burgeoning field of epitranscriptomics, which are predicted to be heavily involved in cognitive function. These include activity-induced RNA modifications, RNA editing, dynamic changes in the secondary structure of RNA, and RNA localization. Each is described with an emphasis on its role in regulating the function of both protein-coding genes, as well as various noncoding regulatory RNAs, and how each might influence learning and memory. PMID- 27669993 TI - Flow-induced HDAC1 phosphorylation and nuclear export in angiogenic sprouting. AB - Angiogenesis requires the coordinated growth and migration of endothelial cells (ECs), with each EC residing in the vessel wall integrating local signals to determine whether to remain quiescent or undergo morphogenesis. These signals include vascular endothelial growth factor (VEGF) and flow-induced mechanical stimuli such as interstitial flow, which are both elevated in the tumor microenvironment. However, it is not clear how VEGF signaling and mechanobiological activation due to interstitial flow cooperate during angiogenesis. Here, we show that endothelial morphogenesis is histone deacetylase 1- (HDAC1) dependent and that interstitial flow increases the phosphorylation of HDAC1, its activity, and its export from the nucleus. Furthermore, we show that HDAC1 inhibition decreases endothelial morphogenesis and matrix metalloproteinase 14 (MMP14) expression. Our results suggest that HDAC1 modulates angiogenesis in response to flow, providing a new target for modulating vascularization in the clinic. PMID- 27669994 TI - Corrigendum to "Haemophilus parasuis induces activation of NF-kappaB and MAP kinase signaling pathways mediated by toll-like receptors" [Mol. Immunol. 65 (2) (2015) 360-366]. PMID- 27669991 TI - LTD-like molecular pathways in developmental synaptic pruning. AB - In long-term depression (LTD) at synapses in the adult brain, synaptic strength is reduced in an experience-dependent manner. LTD thus provides a cellular mechanism for information storage in some forms of learning. A similar activity dependent reduction in synaptic strength also occurs in the developing brain and there provides an essential step in synaptic pruning and the postnatal development of neural circuits. Here we review evidence suggesting that LTD and synaptic pruning share components of their underlying molecular machinery and may thus represent two developmental stages of the same type of synaptic modulation that serve different, but related, functions in neural circuit plasticity. We also assess the relationship between LTD and synaptic pruning in the context of recent findings of LTD dysregulation in several mouse models of autism spectrum disorder (ASD) and discuss whether LTD deficits can indicate impaired pruning processes that are required for proper brain development. PMID- 27669995 TI - Reproductive toxicity and gender differences induced by cadmium telluride quantum dots in an invertebrate model organism. AB - Sexual glands are key sites affected by nanotoxicity, but there is no sensitive assay for measuring reproductive toxicity in animals. The aim of this study was to investigate the toxic effects of cadmium telluride quantum dots (CdTe-QDs) on gonads in a model organism, Bombyx mori. After dorsal vein injection of 0.32 nmol of CdTe-QDs per individual, the QDs passed through the outer membranes of gonads via the generation of ROS in the membranes of spermatocysts and ovarioles, as well as internal germ cells, thereby inducing early germ cell death or malformations via complex mechanisms related to apoptosis and autophagy through mitochondrial and lysosomal pathways. Histological observations of the gonads and quantitative analyses of germ cell development showed that the reproductive toxicity was characterized by obvious male sensitivity. Exposure to QDs in the early stage of males had severe adverse effects on the quantity and quality of sperm, which was the main reason for the occurrence of unfertilized eggs. Ala- or Gly-conjugated QDs could reduce the nanotoxicity of CdTe-QDs during germ cell development and fertilization of their offspring. The results demonstrate that males are preferable models for evaluating the reproductive toxicity of QDs in combined in vivo/in vitro investigations. PMID- 27669996 TI - [How to characterize and treat sleep complaints in bipolar disorders?] AB - OBJECTIVES: Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. METHODS: We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs"). RESULTS: Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders. CONCLUSIONS: BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes. PMID- 27669997 TI - Motor skill changes and neurophysiologic adaptation to recovery-oriented virtual rehabilitation of hand function in a person with subacute stroke: a case study. AB - PURPOSE: The complexity of upper extremity (UE) behavior requires recovery of near normal neuromuscular function to minimize residual disability following a stroke. This requirement places a premium on spontaneous recovery and neuroplastic adaptation to rehabilitation by the lesioned hemisphere. Motor skill learning is frequently cited as a requirement for neuroplasticity. Studies examining the links between training, motor learning, neuroplasticity, and improvements in hand motor function are indicated. METHODS: This case study describes a patient with slow recovering hand and finger movement (Total Upper Extremity Fugl-Meyer examination score = 25/66, Wrist and Hand items = 2/24 on poststroke day 37) following a stroke. The patient received an intensive eight session intervention utilizing simulated activities that focused on the recovery of finger extension, finger individuation, and pinch-grasp force modulation. RESULTS: Over the eight sessions, the patient demonstrated improvements on untrained transfer tasks, which suggest that motor learning had occurred, as well a dramatic increase in hand function and corresponding expansion of the cortical motor map area representing several key muscles of the paretic hand. Recovery of hand function and motor map expansion continued after discharge through the three month retention testing. CONCLUSION: This case study describes a neuroplasticity based intervention for UE hemiparesis and a model for examining the relationship between training, motor skill acquisition, neuroplasticity, and motor function changes. Implications for rehabilitation Intensive hand and finger rehabilitation activities can be added to an in-patient rehabilitation program for persons with subacute stroke. Targeted training of the thumb may have an impact on activity level function in persons with upper extremity hemiparesis. Untrained transfer tasks can be utilized to confirm that training tasks have elicited motor learning. Changes in cortical motor maps can be used to document changes in brain function which can be used to evaluate changes in motor behavior persons with subacute stroke. PMID- 27669998 TI - Onset of nonlinearity in a stochastic model for auto-chemotactic advancing epithelia. AB - We investigate the role of auto-chemotaxis in the growth and motility of an epithelium advancing on a solid substrate. In this process, cells create their own chemoattractant allowing communications among neighbours, thus leading to a signaling pathway. As known, chemotaxis provokes the onset of cellular density gradients and spatial inhomogeneities mostly at the front, a phenomenon able to predict some features revealed in in vitro experiments. A continuous model is proposed where the coupling between the cellular proliferation, the friction on the substrate and chemotaxis is investigated. According to our results, the friction and proliferation stabilize the front whereas auto-chemotaxis is a factor of destabilization. This antagonist role induces a fingering pattern with a selected wavenumber k0. However, in the planar front case, the translational invariance of the experimental set-up gives also a mode at k = 0 and the coupling between these two modes in the nonlinear regime is responsible for the onset of a Hopf-bifurcation. The time-dependent oscillations of patterns observed experimentally can be predicted simply in this continuous non-linear approach. Finally the effects of noise are also investigated below the instability threshold. PMID- 27669999 TI - Risk assessment of high-lying innominate artery with neck surgery. AB - CONCLUSION: A high-lying innominate artery (the upper edge of the innominate artery across the anterior midline of the trachea located 2 cm above the suprasternal notch), a rare situation, may produce disturbance to related anterior cervical tracheal surgery and even cause serious complications. OBJECTIVES: High-lying innominate artery is a high risk factor in anterior cervical tracheal surgery. Pre-operative assessment via imaging technique can help to familiarize the artery and reduce the related disturbance to the surgery. METHODS: A total of 829 patients were selected. Cervical computed tomography (CT) examination was conducted before surgery. The distance between the upper edge of the innominate artery across the anterior midline of the trachea and the suprasternal notch was measured. The exposure of innominate arteries in these cases during surgery was recorded. RESULTS: The upper edge of the innominate artery was located above the suprasternal notch in 26.4% (219/829) of patients. The upper edge of the innominate artery across the anterior midline of the trachea was 2 cm above the suprasternal notch in 18 cases, accounting for 2.2% of all cases, and innominate arteries were exposed in 11 cases (61.1%) during surgery. PMID- 27670002 TI - Nurses need more than public support says report. AB - Nurses can no longer rely on sentimental motives or public support alone if they are to remain at the centre of health care, says a major policy document on the future of nursing agreed at the Royal College of Nursing Council last week. PMID- 27670001 TI - Editorial. AB - Staff at a GP practice in Blackburn have hit upon an inspired method of recruiting new staff - they pray for divine assistance. The all-Christian practice apparently relies on group prayer when a vacancy arises. 'Sometimes it can take a while but we always find someone', says practice nurse Dorothy Vernon. PMID- 27670000 TI - Gram Negative Bacterial Inflammation Ameliorated by the Plasma Protein Beta 2 Glycoprotein I. AB - Lipopolysaccharide (LPS) is a major component of the outer wall of gram negative bacteria. In high doses LPS contributes to the inflammation in gram negative sepsis, and in low doses contributes to the low grade inflammation characteristic of the metabolic syndrome. We wanted to assess the role of beta2-glycoprotein I (beta2GPI) a highly conserved plasma protein and its different biochemical forms in a mouse model of LPS systemic inflammation. Normal and beta2GPI deficient mice were administered LPS through their veins and assessed for a range of inflammation markers in their blood and liver. Different biochemical forms of beta2GPI were measured in normal mice given either saline or LPS. We show that beta2GPI has a significant role in inhibiting LPS induced inflammation. In this study we provide some evidence that beta2GPI serves a protective role in a mouse model of LPS inflammation. This resolves the controversy of previous studies which used LPS and beta2GPI in test tube based models of LPS induced activation of white cells. We also highlight the potential relevance of a newly discovered biochemical form of beta2GPI in LPS mediated inflammation and we speculate that this form has a protective role against LPS induced pathology. PMID- 27670003 TI - Speculation over Bottomley's plans. AB - Health organisations were looking forward to hearing health secretary Virginia Bottomley's plans for her next period of office after last week's Cabinet reshuffle. PMID- 27670005 TI - Library hours. AB - The Royal College of Nursing library in Cavendish Square, London, will open during August on Mondays to Thursdays between 9am and 6pm, and from 9am to 5pm on Fridays. PMID- 27670004 TI - GPs get largest slice of Childbirth grants. AB - Unions have attacked the Government over the level of grants it has awarded for the implementation of Changing Childbirth pilot projects. PMID- 27670006 TI - Three face phone fraud charges. AB - Three nurses suspended from Harlow's Princess Alexandra Hospital after allegations that they made thousands of pounds worth of private telephone calls are to face fraud charges. PMID- 27670007 TI - L205,000 for back injury. AB - A nurse who suffered a serious back injury at work six years ago has been awarded record damages. PMID- 27670008 TI - Slough staff in snack storm. AB - A storm is brewing in Slough ' over the decision to make a new canteen, attached to the outpatient department of Wexham Park Hospital, out of bounds to nurses. PMID- 27670009 TI - Advice on holiday health risks. AB - Travellers are being warned of holiday health risks in a new booklet released last week by the Chief Medical Officer. PMID- 27670010 TI - Nurses fly out to orphanage overwhelmed by refugees. AB - British aid pouring into camps in Zaire to help Rwandan refugees is being backed by an influx of British nurses and doctors. PMID- 27670011 TI - Oh Lord, help us to fill our job vacancy. AB - A Blackburn GP practice has spurned the traditions of NHS recruitment and is relying on the power of prayer to fill its vacant posts. PMID- 27670012 TI - NHS trust in bath death case fined L50,000. AB - A trust was fined L50,(XX) with L6,000 costs after an elderly patient died in the bath when nurses on an understaffed ward left her unattended. PMID- 27670013 TI - CNO backs learning disability training. AB - Concerns that the mental handicap branch of Project 2000 could be dropped have been quashed by the Chief Nursing Officer Yvonne Moores, who last week announced her support for learning disability nurses. PMID- 27670014 TI - Changing childbirth threat to grading. AB - Midwives are being downgraded as managers use the Changing Childbirth report as 'a weapon against midwives'. PMID- 27670016 TI - President calls for separate pay system. AB - The Government must act immediately to introduce a separate pay and grading structure for midwives, newly- elected Royal College of Midwives President Caroline Flint urged in her address to the conference. PMID- 27670017 TI - ? AB - Those in favour: delegates voting in Scarborough last week. PMID- 27670015 TI - National campaign decision. AB - A national campaign to raise mothers' awareness of theChanging Childbirthreport is set to be launched by the RCM. PMID- 27670018 TI - Call for more money for move to community. AB - More money to pay for the transfer of midwifery services to the community was demanded by conference. A motion proposed by the Royal College of Midwives Council called for the 'appropriate level of resources' to be allocated to the primary sector. PMID- 27670019 TI - Call to end open visiting. AB - Midwives last week voted overwhelmingly for an end to open visiting in the wake of the abduction of baby Abbie Humphries from a Nottingham hospital. PMID- 27670020 TI - Danger of car accidents due to overworking. AB - Midwives have been involved in car crashes and mothers have received lower standards of care because many midwives are expected to work excessive hours, the conference heard. PMID- 27670022 TI - Conference supports mothers' choice on water births. AB - Waterbirths should take place only in low risk pregnancies after at least 37 weeks and must be the woman's choice, a position statement launched last week says. There should be no sedation within the last four hours and less than 24 hours spontaneous rupture of membranes. PMID- 27670023 TI - UKCC PREP proposals will cause hardship. AB - Nurses will face hardship if they have to pay for their post-registration education, the Royal College of Nursing warned last week in its response to the United Kingdom Central Council's proposals on PREP. PMID- 27670025 TI - Council considers kitemark for care homes. AB - Nurses working in the independent sector feel vulnerable and need more support, Council heard during a discussion on the recent UKCC report which indicates continuing abuse of the elderly. PMID- 27670024 TI - Subscription rises. AB - Subscriptions could be increased by L3.50, and L6.50 for members who pay by DOCAS, Council agreed. A vote will be taken at the October AGM. PMID- 27670026 TI - ? AB - Last week RCN President June Clark accepted a posthumous award made to Trevor Clay by the Spanish College of Nursing for his 'outstanding contribution to nursing and his great friendship to the international nursing community'. It is the first time this award has been made to a non-Spaniard. From left to right: Taka Oguisso, deputy executive director of the International Council of Nurses, Council Vice Chair Pat Hughes, Council Chair Judith Hunter, RCN General Secretary Christine Hancock, June Clark and Miriam Ovalle Bernal representing the Spanish Royal College of Nursing. PMID- 27670027 TI - Axe attack confirms Welsh Board's worries over care in the community. AB - Psychiatric nurses in Wales feel that care in the community has failed them, following an axe attack on staff at the Princess of Wales Hospital, Bridgend by a man receiving treatment for his mental illness. PMID- 27670028 TI - Report calls for purchasing input from psychiatric nurses. AB - Psychiatric nurses should contribute to purchasing decisions if mental health services are to meet children's needs, according to a national review published last week. PMID- 27670030 TI - ? AB - Old midwives' tale: 'Alyson: healer and midwife' was the title of a play performed in the Old Operating Theatre museum and herb garret at St Thomas' Hospital last week as part of the South Thames Festival. The play tells the story' of a "wise woman' awaiting execution for witchcraft. PMID- 27670031 TI - Child care provision falls far short of shiftworkers' needs. AB - More health care workers use child care facilities during working hours than any other profession - but provision for child care is falling far short of need according to a new report on shiftworkers' childcare needs. PMID- 27670032 TI - RCN slams PRP in brief to Parliament. AB - Individual performance-related pay schemes are unworkable for nurses because they work in teams, co-ordinating different roles and tasks, the Royal College of Nursing has insisted in a briefing to MPs and members of the House of Lords. PMID- 27670033 TI - ? AB - On target: Anthony Stevens and his sister Joanna, raised L500 during last week's 1994 Cadbury Strollerthon. Proceeds from the walk will be divided between a project to help improve the mobility of children with disabilities in the UK and Save the Children overseas schemes. PMID- 27670034 TI - Purchasers are not using private sector. AB - NHS purchasers have not yet used their new freedom to send patients for treatment in the private sector, figures published last week reveal. PMID- 27670035 TI - Northern exposure. AB - Nurses in Alaska have won a battle to be represented by unions in pay bargaining. PMID- 27670036 TI - Research congress attracts 400. AB - The impact of clinical research on nursing practice was one of the key matters for debate at a meeting of nurse scholars from around the globe in Australia. PMID- 27670038 TI - ? AB - Judgement day: Judging for theNursing StandardNurse 94 awards took place in London recently. Pictured, left to right, are five members of the core judging paneL Jenny Hunt, Nursing Practice Consultant at Luton and Dunstable Hospital; James Marr, Consultant Nurse with Tameside Nursing Development Unit; Ainna Fawcett-Henesy, Deputy Director of Nursing at the Department of Health;Nursing Standard'sEditor Norah Casey; and Carol Jones, Matron at the BUPA Hospital, Leicester. PMID- 27670037 TI - RCN praises 'sensible balance' of fetal egg ban for infertility. AB - The RCN has welcomed the ban on using eggs taken from aborted fetuses and dead women, announced last week by the Human Fertilisation and Embryology Authority. PMID- 27670039 TI - Government considers national skin bank. AB - Britain could soon have a national skin bank providing tissue across the country. PMID- 27670040 TI - NHS crime losses halved to L2.1m. AB - Crime in the NHS has fallen for the first time in years. PMID- 27670041 TI - Nurses ideally placed for central role in identifying prostate disease. AB - Nurses should be given a central role in identifying and managing prostate disease, a study in Minnesota has demanded. PMID- 27670042 TI - Improvements in long-term survival rates of child cancer. AB - A study of the long-term survival rates of people who had childhood cancers has revealed increased mortality from treatment, but researchers say the benefits still outweigh the risks. PMID- 27670043 TI - Aspirin speeds up healing of leg ulcers. AB - Aspirin could speed up the healing rate of chronic venous leg ulcers, according to a recent study published in The Lancet. PMID- 27670044 TI - BP and diabetes linked to stroke progression. AB - Systolic blood pressure and the presence of diabetes are associated with progression of acute stroke, Danish research suggests. PMID- 27670045 TI - Ignorance about aspirin risks persist. AB - Despite warnings eight years ago from the Committee on Safety of Medicines, parents are continuing to give children under 12 aspirin. PMID- 27670046 TI - Exhaust suicides and catalytic convertors. AB - Car engine exhaust gases continue to be a hazard, irrespective of the presence of catalytic convertors, according to Aberdeen researchers. PMID- 27670047 TI - Chernobyl fallout and leukaemia incidence. AB - No major public health consequences can be expected as a result of fallout from the Chernobyl nuclear power plant, research suggests. PMID- 27670048 TI - Changes of opinion at CHC conference? AB - FORMER nurse Ray Rowden startled delegates at the Association of Community Health Councils' annual conference in Eastbourne by boldly welcoming some of the health service changes which are more often condemned by health professionals. PMID- 27670049 TI - Malone's your man. AB - BBC RADIO 4 presenter Jim Naughtie is not a happy man. For he is still likely to find health secretary Virginia Bottomley on the other end of his phoneline most mornings. For Mrs Bottomley defied predictions she was heading for a new job, remaining in charge of the Department of Health - at least for another year. PMID- 27670050 TI - Lack of childcare in NHS is causing nurses to quit. AB - HELEN Thomas' nursing ' career has been cut tragically short. Not by disease or redundancy, but by the health system's failure to , recognise one of its employees' most basic needs. Childcare for shiftworkers. PMID- 27670051 TI - Yes, let's change the record please. AB - Thank goodness for a little bit of common sense (Go with the Fo, Letters, July 6). I am sick and fed up with this constant tirade against private nursing homes. PMID- 27670052 TI - Moaning minnies unite on project 2000. AB - In reply to Bruce Fraser's letter (July 6), I never thought I would hear myself described as a 'moaning minnie'. PMID- 27670054 TI - Passing on the word of mouth quickly. AB - Following the public expression by a number of world experts of their personal and professional concerns about chronic mercury poisoning on the BBC Panorama programme (July 11), I assume it will not be long before the. PMID- 27670053 TI - Go farther with a positive attitude. AB - Thank you, Mark Cooper. (The Standard guide to further study, Viewpoint, July 13). That was the most positive article I've read in months. It's encouraging at the beginning of term two of a Project 2000 course to find such a plus on education instead of a load of moans and gripes about one thing and another. PMID- 27670055 TI - Compliments for the complementary. AB - We read with interest the news item 'Complementary therapy first' (June 15) regarding another centre for complementary therapies and research and would like to draw attention to the services offered at The Royal London Homeopathic Hospital NHS Trust. Based in Great Ormond Street, homeopathy and complementary therapies are and have been available on the NHS for many years. PMID- 27670056 TI - Welcome to the real world of caring. AB - The letter 'Mind your backs: NVQs march on', raises the question of the role of the trained nurse in conjunction with the development of level three NVQs. PMID- 27670058 TI - Information exchange. AB - * We are currently engaged in designing admission and discharge documentation for patients undergoing cataract surgery in our new day bed/short stay ward. We hope to keep the paperwork simple and would appreciate information or examples of documentation from anyone with experience in this area. Janet Wright. PMID- 27670057 TI - One in the eye for prescribers. AB - About the news item, 'Potential dangers of steroid eye drops' (Research news, July 13). Any ophthalmic trained nurse or nurse with ophthalmic experience has known for many years the side effects of over-used steroid drops. PMID- 27670059 TI - Yes, no, don't know. AB - Hello there, health care workers! I am glad to say that things have settled down here on my new nursing unit in the last couple of weeks. Nathan has returned to work after his brief spell of helping the police with their enquiries following the computer debacle. He is making rather too much of the experience in my opinion. I have told him that one person's emotional trauma is another person's experiential learning, and he should consider writing it all up in his reflective diary. If he adds it to his professional profile for the next time he is APEL'd, he will probably be awarded a degree on the strength of it. PMID- 27670060 TI - ? AB - "There, there, nurse. Why not write to Viewpoint and tell the world how you feel?" PMID- 27670061 TI - Manual of Critical Care Procedures K Craig editor Springhouse 496pp L21.00 0 87434-691-6. PMID- 27670062 TI - Religion in aging and health Religion in aging and health JS Levin editor SAGE 254pp L19.50 0-8039-5439-5. AB - Religion in Aging and Health: Theoretical Foundations and Methodological Frontiers presents a series of academic reflections and empirical studies about the relationships between religion and health and the process of ageing. Each contributor has an. PMID- 27670063 TI - Nursing informatics Nursing informatics P Wainwright editor Churchill Livingstone 200pp L19.95 0-443-04705-7 [Formula: see text]. AB - When editing a book written by a number of well-known and respected experts in their field, it is often difficult to prevent the final result being a number of loosely connected articles. ThatNursing Informaticsachieves a cohesion leading the reader from chapter to chapter easily and logically reflects well on the editor, Paul Wainwright. PMID- 27670064 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard. Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27670065 TI - The Perfect Match. PMID- 27670066 TI - Most American Association of Oral and Maxillofacial Surgeons Members Have Not Adopted the American Society of Anesthesiologists-Recommended Nil Per Os Guidelines. AB - PURPOSE: The purpose of this study was to determine if American Association of Oral and Maxillofacial Surgeons members have integrated the current American Society of Anesthesiologists (ASA) nil per os (NPO) guidelines into their preoperative instructions. MATERIALS AND METHODS: We designed and implemented a cross-sectional study and enrolled a random sample of private-practice American Association of Oral and Maxillofacial Surgeons members who practice in the United States. The predictor variables were year of graduation from residency, dual degree (MD and DDS or DMD) or single degree, and region. The primary outcome variable was adoption of the ASA NPO guidelines, defined as recommending fasting times of 2 hours for clear liquids and 6 hours for solid foods. To collect data, a systematic online search was implemented. Appropriate univariate and bivariate statistics were computed, and the level of significance was set at .05; in addition, 95% confidence intervals were calculated. RESULTS: The study sample was composed of 431 oral and maxillofacial surgeons (OMSs). Almost all of the study sample (99.1%) did not adopt the ASA guidelines. The fasting recommendations were different from 2 hours for clear liquids and 6 hours for solid foods. However, recommendations of 2 hours or greater for clear liquids were made by 99.8% of OMSs, and recommendations of 6 hours or greater for solid foods were made by 99.3%. Only 4.4% of OMSs made different recommendations for clear liquids and solid foods. No substantial association was found between whether OMSs adopted the most current ASA guidelines and the year they graduated from residency or the obtainment of dual degrees. CONCLUSIONS: OMSs in private practice are overwhelmingly recommending longer fasting times for clear liquids and solid foods on their Web sites when compared with the current ASA guidelines before ambulatory anesthesia. The ASA guidelines are based on meta-analysis; therefore, deviations in practice, although not incorrect, may call for discussion. PMID- 27670067 TI - Effects of Nitrite Addition to IGL-1 Solution on Rat Liver Preservation. AB - BACKGROUND The ability of nitrite to provide protection following ischemia/reperfusion (I/R) has been demonstrated, but its mechanism is still poorly understood. This study aimed to determine the optimal nitrite concentration to add into Institut Georges Lopez (IGL-1) storage solution and to assess its effect on antioxidant enzymes and autophagy. MATERIAL AND METHODS Livers from Sprague-Dawley rats were conserved in IGL-1 for 24 hours at 4 degrees C or in IGL-1 enriched with nitrite at 50, 500 and 1,000 nM, respectively, before being perfused ex-vivo at 37 degrees C for 120 minutes. Sham livers were perfused ex vivo without cold preservation. RESULTS All biological and functional parameters of the preserved livers were significantly impaired as compared to shams. Interestingly, the supplementation of nitrite to IGL-1 protected the liver from I/R injury. Among the doses of nitrite evaluated, the 50 nM was proved efficient: it significantly reduced cytolysis, mitochondrial damage, and lipid peroxidation, and enhanced antioxidant enzyme activity (superoxide dismutase, catalase, and glutathione peroxidase activity) and hepatic function parameters (portal resistance, bile flow, and bromosulfophthalein clearance). In addition, increased levels of the autophagy parameters were observed when 50 nM of nitrite were added to IGL-1 solution, but this effect disappeared completely with higher concentrations of nitrite. CONCLUSIONS It seems that 50 nM of nitrite added to IGL-1 is the optimal concentration able to maintain cell integrity and hepatic function through autophagy induction and oxidative stress prevention. PMID- 27670068 TI - Canine pulmonary vein-to-pulmonary artery ratio: echocardiographic technique and reference intervals. AB - OBJECTIVES: The size of the pulmonary veins (PVs) and pulmonary arteries (PAs) changes in response to hemodynamic alterations caused by physiological events and disease. We sought to create standardized echocardiographic methods for imaging the right ostium of the pulmonary veins (RPVs) and the right pulmonary artery (RPA) using specific landmarks and timing to quantify vessel diameters and phasic changes during the cardiac cycle. ANIMALS: Fifty client-owned healthy dogs prospectively recruited. METHODS: M-mode and 2-dimensional images were obtained from modified right parasternal long and short axis views. Right ostium of the pulmonary veins and RPA measurements were timed with electrical [peak of the QRS complex (RPVQRS and RPAQRS) and end of T wave (RPVT and RPAT)] or mechanical events [RPV and RPA vessels at their respective maximal (RPVMAX; RPAMAX) and minimal (RPVMIN; RPAMIN) diameters]. Right ostium of the pulmonary veins and RPA measurements were also indexed to the aorta. RESULTS: In normal dogs regardless of the echocardiographic view or time in the cardiac cycle, the RPV/RPA ratio approximated 1.0. Mechanically timed fractional changes (distensibility indices) in RPV and RPA diameters did not differ (p=0.99; 36.9% and 36.8%, respectively). ECG-timed fractional changes (distensibility indices) in RPV and RPA diameter were at least 50% smaller than mechanically timed changes (p<0.05). RPV:Ao and RPA:Ao ranged between 0.3 and 0.6, with lower values obtained in diastole and larger values in systole (p<0.0001). Multiple positive and negative deflections were identified on the RPV and RPA M-mode tracings. CONCLUSION: This study provides detailed methodology and 2D and M-mode reference intervals for the RPV and RPA dimensions and the phasic changes during the cardiac cycle of the dog using echocardiography. PMID- 27670069 TI - The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers. AB - Proprotein Convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of cancer and infectious diseases. Inhibitory camelid antibodies were developed, targeting the prototypical PC furin. Kinetic analyses of them revealed an enigmatic non-competitive mechanism, affecting the inhibition of large proprotein-like but not small peptidic substrates. Here we present the crystal structures of furin in complex with the antibody Nb14 and of free Nb14 at resolutions of 2.0 A and 2.3 A, respectively. Nb14 binds at a site distant to the substrate binding pocket to the P-domain of furin. Interestingly, no major conformational changes were observed upon complex formation, neither for the protease nor for the antibody. Inhibition of furin by Nb14 is instead explained by steric exclusion of specific substrate conformers, explaining why Nb14 inhibits the processing of bulky protein substrates but not of small peptide substrates. This mode of action was further supported by modelling studies with the ternary factor X-furin-antibody complex and a mutation that disrupted the interaction interface between furin and the antibody. The observed binding mode of Nb14 suggests a novel approach for the development of highly specific antibody-based proprotein convertase inhibitors. PMID- 27670070 TI - Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1. AB - Thymic selection shapes an appropriate T cell antigen receptor (TCR) repertoire during T cell development. Here, we show that a serine/threonine kinase, protein kinase D (PKD), is crucial for thymocyte positive selection. In T cell-specific PKD-deficient (PKD2/PKD3 double-deficient) mice, the generation of CD4 single positive thymocytes is abrogated. This defect is likely caused by attenuated TCR signalling during positive selection and incomplete CD4 lineage specification in PKD-deficient thymocytes; however, TCR-proximal tyrosine phosphorylation is not affected. PKD is activated in CD4+CD8+ double positive (DP) thymocytes on stimulation with positively selecting peptides. By phosphoproteomic analysis, we identify SH2-containing protein tyrosine phosphatase-1 (SHP-1) as a direct substrate of PKD. Substitution of wild-type SHP-1 by phosphorylation-defective mutant (SHP-1S557A) impairs generation of CD4+ thymocytes. These results suggest that the PKD-SHP-1 axis positively regulates TCR signalling to promote CD4+ T cell development. PMID- 27670071 TI - Effect of different vaccination strategies on IBV QX population dynamics and clinical outbreaks. AB - The extreme variability and rapid evolution of Infectious bronchitis virus (IBV) has always represented the key challenge for its control because of the limited cross-protection among different strains. Several experimental trials have proven a broadening of the protection spectrum when animals are vaccinated with multiple genotypes. Nevertheless, the conditions of vaccine administration in field are so different that the generalization of experimental results is, at least, questionable. In the present study a large scale epidemiological-phylodynamic approach was used to reconstruct the demographic history of the major field genotype (i.e. the QX one) circulating in Italy and Spain. These two countries were selected because, even if they share a comparable epidemiological scenario, the implemented vaccination protocols did not vary in Spain while changed dramatically in Italy over the time period considered. One hundred and ninety five Italian and 98 Spanish non-recombinant sequences of the hyper-variable region of the S1 gene obtained between 2012 and 2016 were analyzed using a serial coalescent-based approach to reconstruct viral population history over time. While the IBV QX population dynamics remained constant in Spain, a much more complex pattern was evidenced in Italy; both in terms of viral population size and clinical outbreak frequency. Remarkably, a strong association with changes in vaccination strategies was recognized. This allowed demonstrating, by accomplishing all Hill's criteria for causation, the cause-effect relationship between the vaccine administration/withdrawal and the variation in viral population dynamics and, above all, IBV related outbreaks. Thus, a robust confirmation about the efficacy of IBV vaccination in field conditions was provided. Additionally, the history herein reported testifies the primary importance of rigorously planning not only the intervention strategies but also their monitoring and evaluation. PMID- 27670072 TI - Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination. AB - In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8+ T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8+ T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. PMID- 27670074 TI - Trends in compliance with two-dose influenza vaccine recommendations in children aged 6 months through 8 years, 2010-2015. AB - BACKGROUND: Children aged 6 months through 8 years may require two doses of influenza vaccine for adequate immune response against the disease. However, poor two-dose compliance has been reported in the literature. METHODS: We analyzed data for >2.6million children from six immunization information system (IIS) sentinel sites, and assessed full vaccination coverage and two-dose compliance in the 2010-2015 influenza vaccination seasons. Full vaccination was defined as having received at least the recommended number of influenza vaccine doses (one or two), based on recommendations from the Advisory Committee on Immunization Practices. Two-dose compliance was defined as the percentage of children during each season who received at least two doses of influenza vaccine among those who required two doses and initiated the series. RESULTS: Across seasons, ?1-dose influenza vaccination coverage was mainly unchanged among 6-23montholds (range: 60.9-66.6%), 2-4yearolds (range: 44.8-47.4%), and 5-8yearolds (range: 34.5 38.9%). However, full vaccination coverage showed increasing trends from 2010-11 season to 2014-15 season (6-23months: 43.0-46.5%; 2-4yearolds: 26.3-39.7%; 5 8yearolds, 18.5-33.9%). Across seasons, two-dose compliance remained modest in children 6-23months (range: 63.3-67.6%) and very low in older children (range: 11.6-18.7% in children 2-4yearsand6.8-13.3% in children 5-8years). In the 2014-15 season, among children who required and received 2 doses, only half completed the two-dose series before influenza activity peaked. CONCLUSIONS: Improved messaging of the two-dose influenza vaccine recommendations is needed for providers and parents. Providers are encouraged to determine a child's eligibility for two doses of influenza vaccine using the child's vaccination history, and to vaccinate children early in the season so that two-dose series are completed before influenza peaks. PMID- 27670075 TI - Supramolecular peptide hydrogel adjuvanted subunit vaccine elicits protective antibody responses against West Nile virus. AB - A crucial issue in vaccine development is to balance safety with immunogenicity. The low immunogenicity of most subunit antigens warrants a search for adjuvants able to stimulate both cell-mediated and humoral immunity. In recent years, successful applications of nanotechnology and bioengineering in the field of vaccine development have enabled the production of novel adjuvant technologies. In this work, we investigated totally synthetic and supramolecular peptide hydrogels as novel vaccine adjuvants in conjunction with the immunoprotective envelope protein domain III (EIII) of West Nile virus as an immunogen in a mouse model. Our results indicate that, compared to the clinically approved adjuvant alum, peptide hydrogel adjuvanted antigen elicited stronger antibody responses and conferred significant protection against mortality after virus challenge. The high chemical definition and biocompatibility of self-assembling peptide hydrogels makes them attractive as immune adjuvants for the production of subunit vaccines against viral and bacterial infections where antibody-mediated protection is desirable. PMID- 27670073 TI - Canine H3N8 influenza vaccines partially protect mice against the canine H3N2 strain currently circulating in the United States. AB - Influenza A viruses infect many species and cross-species transmission occurs occasionally. An equine H3N8 influenza virus began circulating in dogs in 1999 and an avian H3N2 influenza virus began circulating in dogs in 2006. The canine H3N8 (cH3N8) viral strain has become endemic in parts of the United States and there is a commercially available vaccine against this strain. The canine H3N2 (cH3N2) strain did not circulate widely in the United States until 2015. Here, we used a mouse model to determine if the cH3N8 and cH3N2 strains are antigenically related and if a commercially available cH3N8 vaccine protects animals against the cH3N2 outbreak strain. We find that the cH3N8 vaccine elicits antibodies that react to internal viral proteins and the hemagglutinin stalk region of cH3N2 viruses. These antibodies do not provide sterilizing immunity against cH3N2 infection, but these antibodies limit cH3N2 replication in the lung. PMID- 27670076 TI - Improving cold chain systems: Challenges and solutions. AB - While a number of new vaccines have been rolled out across the developing world (with more vaccines in the pipeline), cold chain systems are struggling to efficiently support national immunization programs in ensuring the availability of safe and potent vaccines. This article reflects on the Clinton Health Access Initiative, Inc. (CHAI) experience working since 2010 with national immunization programs and partners to improve vaccines cold chains in 10 countries-Ethiopia, Nigeria, Kenya, Malawi, Tanzania, Uganda, Cameroon, Mozambique, Lesotho and India - to identify the root causes and solutions for three common issues limiting cold chain performance. Key recommendations include: Collectively, the solutions detailed in this article chart a path to substantially improving the performance of the cold chain. Combined with an enabling global and in-country environment, it is possible to eliminate cold chain issues as a substantial barrier to effective and full immunization coverage over the next few years. PMID- 27670077 TI - Informing rubella vaccination strategies in East Java, Indonesia through transmission modelling. AB - An estimated 110,000 babies are born with congenital rubella syndrome (CRS) worldwide annually; a significant proportion of cases occur in Southeast Asia. Rubella vaccine programs have led to successful control of rubella and CRS, and even the elimination of disease in many countries. However, if vaccination is poorly implemented it might increase the number of women reaching childbearing age who remain susceptible to rubella and thereby paradoxically increase CRS. We used an age-structured transmission model to compare seven alternative vaccine strategies for their impact on reducing CRS disease burden in East Java, a setting which is yet to implement a rubella vaccine program. We also investigated the robustness of model predictions to variation in vaccine coverage and other key epidemiological factors. Without rubella vaccination, approximately 700 babies are estimated to be born with CRS in East Java every year at an incidence of 0.77 per 1000live births. This incidence could be reduced to 0.0045 per 1000 live births associated with 99.9% annual reduction in rubella infections after 20 years if the existing two doses of measles vaccine are substituted with two doses of measles plus rubella combination vaccine with the same coverage (87.8% of 9 month-old infants and 80% of 6-year-old children). By comparison a single dose of rubella vaccine will take longer to reduce the burden of rubella and CRS and will be less robust to lower vaccine coverage. While the findings of this study should be informative for settings similar to East Java, the conclusions are dependent on vaccine coverage which would need consideration before applying to all of Indonesia and elsewhere in Asia. PMID- 27670078 TI - Role of a sensor histidine kinase ChiS of Vibrio cholerae in pathogenesis. AB - Vibrio cholera survival in an aquatic environment depends on chitin utilization pathway that requires two factors, chitin binding protein and chitinases. The chitinases and the chitin utilization pathway are regulated by a two-component sensor histidine kinase ChiS in V. cholerae. In recent studies these two factors are also shown to be involved in V. cholerae pathogenesis. However, the role played by their upstream regulator ChiS in pathogenesis is yet to be known. In this study, we investigated the activation of ChiS in presence of mucin and its functional role in pathogenesis. We found ChiS is activated in mucin supplemented media. The isogenic chiS mutant (ChiS-) showed less growth compared to the wild type strain (ChiS+) in the presence of mucin supplemented media. The ChiS- strain also showed highly retarded motility as well as mucin layer penetration in vitro. Our result also showed that ChiS was important for adherence and survival in HT 29 cell. These observations indicate that ChiS is activated in presence of intestinal mucin and subsequently switch on the chitin utilization pathway. In animal models, our results also supported the in vitro observation. We found reduced fluid accumulation and colonization during infection with ChiS- strain. We also found ChiS- mutant with reduced expression of ctxA, toxT and tcpA. The cumulative effect of these events made V. cholerae ChiS- strain hypovirulent. Hence, we propose that ChiS plays a vital role in V. cholerae pathogenesis. PMID- 27670079 TI - The JRC Nanomaterials Repository: A unique facility providing representative test materials for nanoEHS research. AB - The European Commission has established a Nanomaterials Repository that hosts industrially manufactured nanomaterials that are distributed world-wide for safety testing of nanomaterials. In a first instance these materials were tested in the OECD Testing Programme. They have then also been tested in several EU funded research projects. The JRC Repository of Nanomaterials has thus developed into serving the global scientific community active in the nanoEHS (regulatory) research. The unique Repository facility is a state-of-the-art installation that allows customised sub-sampling under the safest possible conditions, with traceable final sample vials distributed world-wide for research purposes. This paper describes the design of the Repository to perform a semi-automated subsampling procedure, offering high degree of flexibility and precision in the preparation of NM vials for customers, while guaranteeing the safety of the operators, and environmental protection. The JRC nanomaterials are representative for part of the world NMs market. Their wide use world-wide facilitates the generation of comparable and reliable experimental results and datasets in (regulatory) research by the scientific community, ultimately supporting the further development of the OECD regulatory test guidelines. PMID- 27670080 TI - Temporal kinetics of organ damage in copper toxicity: A histopathological correlation in rat model. AB - Excess of copper is toxic to different organs. We aim to study the histopathological changes of liver, kidney, and brain following oral CuSO4 exposure for different duration and doses in rat model. Fifty-four males Wistar rats (205 +/- 10 g) were included and divided into control (group-I) and experimental (group-II and III) arms. An oral dose of 100 and 200 mg/kgBWt/Day CuSO4 was given to group-II and III respectively and group-I received normal saline by gavage. Six rats from each group were sacrificed on days 30, 60 and 90 for biochemical and histopathological examinations. The histopathological changes were graded on 1-5 scores and correlated with respective laboratory parameters. The organ functions were worsened in experimental group with increasing dose and time. Histopathological study revealed edema, hemorrhage, necrosis and fibrosis/gliosis in experimental group. The worst histopathological severity score ranged from 4 to 5(median 5) in liver, 3-5(median 4) in kidney and 4 5(median 5) in brain. The edema and hemorrhage were more marked at 30 days and fibrosis/gliosis at 90 days. In conclusion, high-dose Cu toxicity results in structural damage to liver, kidney, and brain that correlates with organ dysfunction, Cu, GSH, TAC, and MDA concentrations. Liver damage is more severe and occurs earlier than other organs. PMID- 27670081 TI - Modulation of heat shock protein 90 affects TGF-beta-induced collagen synthesis in human dermal fibroblast cells. AB - Heat shock protein 90 is a chaperone molecule that aids in proper folding of target proteins. Recently, heat shock protein 90 was found to play a role in would healing through regulation of fibroblast functions. The aim of the present study was to investigate the role of heat shock protein 90 in collagen synthesis in human dermal fibroblasts. The effects of transforming growth factor-beta, 17-N allylamino-17-demethoxygeldanamycin, and transfection of heat shock protein 90 were evaluated by real-time PCR, western blot, and immunofluorescence assays. The Smad 2/3 and Akt pathways were evaluated to identify the signaling pathways involved in collagen synthesis. Heat shock protein 90 and collagen levels were compared in keloid and control tissues by immunohistochemical analysis. The expression of collagen was significantly increased after treatment with transforming growth factor-beta, while 17-N-allylamino-17-demethoxygeldanamycin inhibited transforming growth factor-beta-induced collagen synthesis. Overexpression of heat shock protein 90 itself with or without transforming growth factor-beta increased collagen synthesis. These effects were dependent on Smad 2/3 pathway signaling. Finally, expression of heat shock protein 90 was increased in keloid tissue compared with control tissues. Taken together, these results demonstrate that modulation of heat shock protein 90 influences transforming growth factor-beta-induced collagen synthesis via regulation of Smad 2/3 phosphorylation. PMID- 27670082 TI - Identification of Stem Cells in the Epithelium of the Stomach Corpus and Antrum of Mice. AB - BACKGROUND & AIMS: Little is known about the mechanisms of gastric carcinogenesis, partly because it has been a challenge to identify characterize gastric stem cells. Runx genes regulate development and their products are transcription factors associated with cancer development. A Runx1 enhancer element, eR1, is a marker of hematopoietic stem cells. We studied expression from eR1 in the stomach and the roles of gastric stem cells in gastric carcinogenesis in transgenic mice. METHODS: We used in situ hybridization and immunofluorescence analyses to study expression of Runx1 in gastric tissues from C57BL/6 (control) mice. We then created mice that expressed enhanced green fluorescent protein (EGFP) or CreERT2 under the control of eR1 (eR1-CreERT2;Rosa-Lox-Stop-Lox [LSL] tdTomato, eR1-CreERT2;Rosa-LSL-EYFP mice). Gastric tissues were collected and lineage-tracing experiments were performed. Gastric organoids were cultured from eR1-CreERT2(5-2);Rosa-LSL-tdTomato mice and immunofluorescence analyses were performed. We investigated the effects of expressing oncogenic mutations in stem cells under control of eR1 using eR1-CreERT2;LSL-KrasG12D/+ mice; gastric tissues were collected and analyzed by histology and immunofluorescence. RESULTS: Most proliferation occurred in the isthmus; 86% of proliferating cells were RUNX1 positive and 76% were MUC5AC-positive. In eR1-EGFP mice, EGFP signals were detected mainly in the upper part of the gastric unit, and 83% of EGFP-positive cells were located in the isthmus/pit region. We found that eR1 marked undifferentiated stem cells in the isthmus and a smaller number of terminally differentiated chief cells at the base. eR1 also marked cells in the pyloric gland in the antrum. Lineage-tracing experiments demonstrated that stem cells in the isthmus and antrum continuously gave rise to mature cells to maintain the gastric unit. eR1-positive cells in the isthmus and pyloric gland generated organoid cultures in vitro. In eR1-CreERT2;LSL-Kras G12D/+ mice, MUC5AC-positive cells rapidly differentiated from stem cells in the isthmus, resulting in distinct metaplastic lesions similar to that observed in human gastric atrophy. CONCLUSIONS: Using lineage-tracing experiments in mice, we found that a Runx1 enhancer element, eR1, promotes its expression in the isthmus stem cells of stomach corpus as well as pyloric gland in the antrum. We were able to use eR1 to express oncogenic mutations in gastric stem cells, proving a new model for studies of gastric carcinogenesis. PMID- 27670083 TI - Identification and characterization of two Croquemort homologues in penaeid shrimp Litopenaeus vannamei. AB - Croquemort, the homologue of human CD36, is a member of class B scavenger receptors, which is involved in bacteria phagocytosis and cytokins release. However, there is still less information about Croquemort in crustaceans. Here, a Croquemort from Pacific white shrimp Litopenaeus vannamei (LvCroquemort) and its truncated form (LvCroquemort-S1) cDNA sequences were identified, characterized and their role in bacteria clearance was investigated. The deduced protein of LvCroquemort is 533 amino acids and contains typical domains of CD36: the N terminus and C-terminus in cytoplasm, two transmembrane regions and a large extracellular loop-like domain. However, LvCroquemort-S1 losses partial cDNA sequence in its middle and its deduced protein losses the C-terminal transmembrane region and C-terminus in cytoplasm, the latter of which is found participating in cytokins release in human CD36. LvCroquemort transcript is highly expressed in gills, hemocytes, testis and slightly in heart, hepatopancreas and nerve. Besides, its responses to bacteria Vibrio anguillarum and white spot syndrome virus were examined. Knock-down of LvCroquemort by specific dsRNA reduces bacteria clearance. These initial data will help to further understand roles of Croquemort in crustacean innate immunity. PMID- 27670084 TI - Insights into the regulation of the MXR response in haemocytes of the Mediterranean mussel (Mytilus galloprovincialis). AB - This study investigated functional and transcriptional modulation of the Multixenobiotic resistance (MXR) system as a cytoprotective mechanism contributing to the physiological chemoresistance of haemocytes in the Mediterranean mussel. Basal transport activity was assessed using the model substrate rhodamine 123 and specific inhibitors for the MXR-related transporters P-glycoprotein (ABCB mRNA) and Multidrug resistance-related protein (ABCC mRNA). Results showed that MXR activity in mussel haemocytes was mainly supported by the Mrp-mediated efflux. In agreement, ABCC was expressed at higher levels than ABCB. Activation of the cyclic-AMP (cAMP) dependent protein kinase A (PKA) resulted in increased rhodamine efflux, which was counteracted by the selective PKA inhibitor H89. Although serotonin, a physiological modulator of cAMP/PKA signaling and ABCB transcription in haemocytes, did not affect basal MXR transport, the environmental pharmaceuticals fluoxetine, propranolol, and carbamazepine, which interact in different ways with the adrenergic and serotoninergic pathways, were showed to act as modulators and substrates of MXR-related transporters and to affect cell viability. While the increased MXR activity may have lowered the cytotoxic effects of propranolol and carbamazepine, the lack of MXR efflux induction by fluoxetine may play a role in the observed cytotoxicity of the compound. PMID- 27670085 TI - Feeding pyridoxine prevents Saprolegnia parasitica infection in fish Labeo rohita. AB - A 60-day experiment was carried out to delineate the role of dietary pyridoxine (DP) in Labeo rohita fingerlings in modulating immunity and prevention of fungal infection. Two hundred and seventy fingerlings were randomly distributed into three treatments in triplicates. Three iso-caloric and iso-nitrogenous purified diets were prepared with graded levels of pyridoxine. Three experimental groups were C (0.0% DP), T1 (0.01% DP) and T2 (0.02% DP). The role of dietary pyridoxine in modulating immunity and prevention of fungal infection was assessed by haemato immunological parameters like erythrocyte counts (EC), leucocyte counts (LC), haemoglobulin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), nitro-blue tetrazolium (NBT), phagocytic activity, albumin, globulin, total plasma protein, albumin/globulin and by challenge study with Saprolegnia parasitica, where relative percentage survival (RPS) were recorded. Hb, PCV, MCV, MCH, NBT, total plasma protein, albumin, globulin contents, lysozyme and phagocytic activity was significantly (P < 0.05) higher in DP fed group. Significantly (P < 0.05) higher RPS was recorded from T2 group fed with 0.02% DP for 45 days. Hence, DP has the capacity to stimulate nonspecific immunity and increase resistance to S. parasitica infection in L. rohita fingerlings. PMID- 27670086 TI - Dietary supplementation with xylanase-expressing B. amyloliquefaciens R8 improves growth performance and enhances immunity against Aeromonas hydrophila in Nile tilapia (Oreochromis niloticus). AB - Bacillus amyloliquefaciens has attracted attention as a probiotic in aquaculture due to its immunostimulatory activity against pathogenic infection. Xylanases are extensively used in animal feed to degrade plant ingredients, enhancing nutrient utilization and increasing the growth rate of various animals. In the present study, the effects of dietary supplementation with B. amyloliquefaciens and xylanase-expressing B. amyloliquefaciens R8 on the growth of Nile tilapia (Oreochromis niloticus) and immunity against Aeromonas hydrophila were evaluated. The results showed that the xylanase activity in the intestine, weight gain (WG), feed efficiency (FE) and condition factor (CF) of Nile tilapia fed B. amyloliquefaciens R8 for 2 months were significantly increased compared with those of the fish fed the control diet and B. amyloliquefaciens. Moreover, the mRNA expression of growth- and metabolism-related genes, such as insulin-like growth factor-1 (igf-1), glucokinase (GK), glucose-6-phosphate 1-dehydrogenase (G6PD), and glucose-6-phosphatase (G6Pase), was significantly induced in Nile tilapia fed administered B. amyloliquefaciens R8, and this group also exhibited a higher survival rate than the control fish following a challenge with A. hydrophila. The phagocytic activity and respiratory burst activity of head kidney leukocytes as well as the serum lysozyme activity of B. amyloliquefaciens R8-fed Nile tilapia were significantly higher than those of fish fed the control diet for 2 months. Superoxide dismutase (SOD) levels in the head kidney leukocytes of Nile tilapia fed B. amyloliquefaciens R8 differed from those of fish fed the control diet, but this was not significant. These results indicate that dietary supplementation with xylanase-expressing B. amyloliquefaciens R8 improves growth performance and enhances immunity and disease resistance against A. hydrophila in Nile tilapia. PMID- 27670088 TI - The longitudinal relationship between post-traumatic stress disorder and perceived social support in survivors of traumatic injury. AB - BACKGROUND: Although perceived social support is thought to be a strong predictor of psychological outcomes following trauma exposure, the temporal relationship between perceived positive and negative social support and post-traumatic stress disorder (PTSD) symptoms has not been empirically established. This study investigated the temporal sequencing of perceived positive social support, perceived negative social support, and PTSD symptoms in the 6 years following trauma exposure among survivors of traumatic injury. METHOD: Participants were 1132 trauma survivors initially assessed upon admission to one of four Level 1 trauma hospitals in Australia after experiencing a traumatic injury. Participants were followed up at 3 months, 12 months, 24 months, and 6 years after the traumatic event. RESULTS: Latent difference score analyses revealed that greater severity of PTSD symptoms predicted subsequent increases in perceived negative social support at each time-point. Greater severity of PTSD symptoms predicted subsequent decreases in perceived positive social support between 3 and 12 months. High levels of perceived positive or negative social support did not predict subsequent changes in PTSD symptoms at any time-point. CONCLUSIONS: Results highlight the impact of PTSD symptoms on subsequent perceived social support, regardless of the type of support provided. The finding that perceived social support does not influence subsequent PTSD symptoms is novel, and indicates that the relationship between PTSD and perceived social support may be unidirectional. PMID- 27670087 TI - Flexible peptide recognition by HLA-DR triggers specific autoimmune T-cell responses in autoimmune thyroiditis and diabetes. AB - Autoimmune polyglandular syndrome 3 variant (APS3v) refers to the co-occurrence of autoimmune thyroiditis (AITD) and type 1 diabetes (T1D) within the same individual. HLA class II confers the strongest susceptibility to APS3v. We previously identified a unique amino acid signature of the HLA-DR pocket (designated APS3v HLA-DR pocket) that predisposes to APS3v. We hypothesized that both thyroid and islet peptides can be presented by the unique APS3v HLA-DR pocket, triggering AITD + T1D together. To test this hypothesis we screened islet and thyroid peptides for their ability to bind to the APS3v HLA-DR pocket. Virtual screen of all possible thyroglobulin (Tg), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), insulin (Ins), and glutamic acid decarboxylase 65 (GAD65) peptides identified 36 peptides that bound to this unique pocket. In vitro binding assays using baculovirus-produced recombinant APS3v HLA-DR identified 11 thyroid/islet peptides (of the 36 predicted binders) that bound with high affinity. By immunizing humanized HLA-DR3 mice carrying the APS3v HLA-DR pocket we identified 4 peptides (Tg.1571, GAD.492, TPO.758, TPO.338) that were presented by antigen presenting cells and elicited T-cell response. We conclude that both thyroid and islet peptides can bind to this flexible APS3v HLA DR pocket and induce thyroid and islet specific T-cell responses. These findings set the stage to developing specific inhibitors of the APS3v HLA-DR pocket as a precision medicine approach to treating or preventing APS3v in patients that carry this genetic HLA-DR pocket variant. PMID- 27670089 TI - Quality in provision of maternity services: the missing link in health-care investments in LMICs? PMID- 27670090 TI - Quality of basic maternal care functions in health facilities of five African countries: an analysis of national health system surveys. AB - BACKGROUND: Global efforts to increase births at health-care facilities might not reduce maternal or newborn mortality if quality of care is insufficient. However, little systematic evidence exists for the quality at health facilities caring for women and newborn babies in low-income countries. We analysed the quality of basic maternal care functions and its association with volume of deliveries and surgical capacity in health-care facilities in five sub-Saharan African countries. METHODS: In this analysis, we combined nationally representative health system surveys (Service Provision Assessments by the Demographic and Health Survery Programme) with data for volume of deliveries and quality of delivery care from Kenya, Namibia, Rwanda, Tanzania, and Uganda. We measured the quality of basic maternal care functions in delivery facilities using an index of 12 indicators of structure and processes of care, including infrastructure and use of evidence-based routine and emergency care interventions. We regressed the quality index on volume of births and confounders (public or privately managed, availability of antiretroviral therapy services, availability of skilled staffing, and country) stratified by facility type: primary (no caesarean capacity) or secondary (has caesarean capacity) care facilities. The Harvard University Human Research Protection Program approved this analysis as exempt from human subjects review. FINDINGS: The national surveys were completed between April, 2006, and May, 2010. Our sample consisted of 1715 (93%) of 1842 health care facilities that provided normal delivery service, after exclusion of facilities with missing (n=126) or invalid (n=1) data. 1511 (88%) study facilities (site of 276 965 [44%] of 622 864 facility births) did not have caesarean section capacity (primary care facilities). Quality of basic maternal care functions was substantially lower in primary (index score 0.38) than secondary care facilities (0.77). Low delivery volume was consistently associated with poor quality, with differences in quality between the lowest versus highest volume facilities of -0.22 (95% CI -0.26 to -0.19) in primary care facilities and -0.17 (-0.21 to -0.11) in secondary care facilities. INTERPRETATION: More than 40% of facility deliveries in these five African countries occurred in primary care facilities, which scored poorly on basic measures of maternal care quality. Facilities with caesarean section capacity, particularly those with birth volumes higher than 500 per year, had higher scores for maternal care quality. Low-income and middle-income countries should systematically assess and improve the quality of delivery care in health facilities to accelerate reduction of maternal and newborn deaths. FUNDING: None. PMID- 27670091 TI - Mining Big Data in biomedicine and health care. PMID- 27670092 TI - Siatic nerve: beyond the sacral foramen. AB - Sciatica may result from pathologies affecting the nerve both in its intraspinal and extraspinal course. In daily routine, the vast majority of cases are caused by herniation of the lumbar discs compressing the neural roots. Extraspinal causes of sciatic pain are usually underestimated and the imaging study may be completed after reporting the lumbar MRIs. However, early diagnosis of the exact etiology of sciatica is paramount for both relieving the symptoms and preventing any additional neurologic injury. In this pictorial assay, some relatively rare causes of sciatic neuralgia along the route of the sciatic nerve after leaving the sacral foramen will be displayed. PMID- 27670093 TI - Isotretinoin treatment in a patient with known peanut allergy and positive IgE test results for soybean. PMID- 27670095 TI - Investigation of bombesin peptide as a targeting ligand for the gastrin releasing peptide (GRP) receptor. AB - Gastrin releasing peptide (GRP) receptor (GRPR), a bombesin family receptor, is overexpressed in many cancers including breast, prostate, pancreatic and lung. The targeting of therapeutics to GRPR can be achieved using the full-length (14 amino acid) GRP analogue Bombesin (BBN) or the truncated BBN(6-14) sequence, both of which bind GRPR with high affinity and specificity. In this study, we have investigated the level of GRPR expression in various cancerous (Caco-2, HeLa, LNCap, MDA-MB-231, and PC-3) and non-cancerous (WPMY-1) cell lines using a western blotting approach. Such information is currently lacking in the literature, and is therefore of importance for the in vitro assessment of GRPR targeted therapeutics. Of the cell lines assessed, the PC-3 (prostate cancer) and Caco-2 (colon cancer) cell lines demonstrated the highest and lowest levels of GRPR expression respectively. Using this information, we further investigated the cellular uptake of carboxyfluorescein-labelled BBN and BBN(6-14) peptides by flow cytometry and confocal microscopy using cell lines that express GRPR (Caco-2, HeLa, PC-3). The uptake of each of these peptides was similar, suggesting that the shorter BBN(6-14) peptide is sufficient for GRPR targeting. Further, the uptake of these peptides could be inhibited by competition with unlabelled BBN peptides, suggesting their cellular uptake is GRPR-mediated, while the level of BBN uptake (as measured by flow cytometry) was found to be directly proportional to the level of GRPR expression. Overall, the information obtained from these studies provides useful information for the in vitro assessment of GRPR targeted therapeutics. PMID- 27670094 TI - Gonadal hormone modulation of ?9-tetrahydrocannabinol-induced antinociception and metabolism in female versus male rats. AB - The gonadal hormones testosterone (T) in adult males and estradiol (E2) in adult females have been reported to modulate behavioral effects of ?9 tetrahydrocannabinol (THC). This study determined whether activational effects of T and E2 are sex-specific, and whether hormones modulate production of the active metabolite 11-hydroxy-THC (11-OH-THC) and the inactive metabolite 11-nor-9 carboxy-THC (THC-COOH). Adult male and female rats were gonadectomized (GDX) and treated with nothing (0), T (10-mm Silastic capsule/100g body weight), or E2 (1 mm Silastic capsule/rat). Three weeks later, saline or the cytochrome P450 inhibitor proadifen (25mg/kg; to block THC metabolism and boost THC's effects) was injected i.p.; 1h later, vehicle or THC (3mg/kg females, 5mg/kg males) was injected i.p., and rats were tested for antinociceptive and motoric effects 15 240min post-injection. T did not consistently alter THC-induced antinociception in males, but decreased it in females (tail withdrawal test). Conversely, T decreased THC-induced catalepsy in males, but had no effect in females. E2 did not alter THC-induced antinociception in females, but enhanced it in males. The discrepant effects of T and E2 on males' and females' behavioral responses to THC suggests that sexual differentiation of THC sensitivity is not simply due to activational effects of hormones, but also occurs via organizational hormone or sex chromosome effects. Analysis of serum showed that proadifen increased THC levels, E2 increased 11-OH-THC in GDX males, and T decreased 11-OH-THC (and to a lesser extent, THC) in GDX females. Thus, hormone modulation of THC's behavioral effects is caused in part by hormone modulation of THC oxidation to its active metabolite. However, the fact that hormone modulation of metabolism did not alter THC sensitivity similarly on all behavioral measures within each sex suggests that other mechanisms also play a role in gonadal hormone modulation of THC sensitivity in adult rats. PMID- 27670096 TI - On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions. AB - A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma (A-549 lung, HCT-116 colon, and MCF-7 breast) cell lines and the normal bronquial epithelial BEAS-2B cells. Cathodic reduction potentials (shifting from -1.463 to 1.570V) reveal that the platinum(IV) compounds under study would be highly reluctant to be reduced in a biological environment. Actually ascorbic acid was not able to reduce complex 3a', the most prone to be reduced according its reduction potential, over a period of one week. These results suggest an intrinsic activity for the investigated platinum(IV) complexes (3a, 3a' and 3b'), which exhibit a remarkable cytotoxicity effectiveness (with IC50 values in the low micromolar range), even greater than that of cisplatin. The IC50 for A-549 lung cells and clog P values were found to follow the same trend: 3b'>3a'>3a. However, no correlation was observed between reduction potential and in vitro activity. As a representative example, cyclometallated platinum(IV) compound 3a', exercise its antiproliferative activity directly over non-microcytic A-549 lung cancer cells through a mixture of cell cycle arrest (13% arrest at G1 phase and 46% arrest at G2 phase) and apoptosis induction (increase of early apoptosis by 30 times with regard to control). To gain further insights into the mode of action of the investigated platinum(IV) complexes, drug uptake, cathepsin B inhibition and ROS generation were also evaluated. Interestingly an increased ROS generation could be related with the antiproliferative activity of the cyclometallated platinum(IV) series under study in the cisplatin-resistant A-549 lung and HCT-116 cancer cell lines. PMID- 27670097 TI - Effect of lysine methylation and acetylation on the RNA recognition and cellular uptake of Tat-derived peptides. AB - The two lysine (Lys) residues in the human immunodeficiency virus trans-activator of transcription protein (HIV Tat protein) basic region (residues 47-57) are crucial for two bioactivities: RNA recognition and cellular uptake. Since the post-translational modifications of these two Lys residues affect the biological function of the Tat protein, we investigated the effect of methylation and acetylation of Lys50 and Lys51 in Tat-derived peptides on the two bioactivities. Tat-derived peptides, in which each lysine was replaced with a methylated- or acetylated-Lys, were synthesized by solid phase peptide synthesis. TAR RNA recognition of the peptides was studied by electrophoretic mobility shift assays. Cellular uptake of the peptides into Jurkat cells was determined by flow cytometry. Our results showed that acetylation of either Lys residue attenuated both bioactivities. In contrast, the effect of Lys methylation on the bioactivities depended on position and number of methyl groups. These findings should be useful for the development of functional molecules containing ammonium groups for RNA recognition to affect biological processes and for cellular uptake for drug delivery. PMID- 27670098 TI - Discovery of a novel chimeric ubenimex-gemcitabine with potent oral antitumor activity. AB - Herein, a novel mutual prodrug BC-A1 was discovered by integrating ubenimex and gemcitabine into one molecule. Biological characterization revealed that compound BC-A1 could maintain both the anti-CD13 activity of ubenimex and the cytotoxic activity of gemcitabine in vitro. Further characterization also demonstrated that compound BC-A1 exhibited significant anti-invasion and anti-angiogenesis effects in vitro. The preliminary stability test of BC-A1 revealed that it could release gemcitabine in vitro. The in vivo anti-tumor results in liver cancer showed that at the same dosage, oral administration of BC-A1 was as potent as intraperitoneal administration of gemcitabine. This warranted the further research and development of the orally active prodrug BC-A1 because gemcitabine can not be orally administrated in clinic. PMID- 27670099 TI - Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors. AB - Molecular modeling of unbound tricyclic guanine scaffolds indicated that they can serve as effective bioisosteric replacements of xanthines. This notion was further confirmed by a combination of X-ray crystallography and SAR studies, indicating that tricyclic guanine DPP4 inhibitors mimic the binding mode of xanthine inhibitors, exemplified by linagliptin. Realization of the bioisosteric relationship between these scaffolds potentially will lead to a wider application of cyclic guanines as xanthine replacements in drug discovery programs for a variety of biological targets. Newly designed DPP4 inhibitors achieved sub nanomolar potency range and demonstrated oral activity in vivo in mouse glucose tolerance test. PMID- 27670100 TI - Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study. AB - A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% cytotoxic concentration (CC50), 50% inhibiting concentration (IC50) and selectivity index (SI) were calculated for each compound. It was found that some of synthesized benzimidazole derivatives (7 of 22, 32%) possess strong virus inhibiting activity against pandemic influenza virus (IC50's in low micromolar range) with quite moderate cytotoxicity (CC50 in the range of thousands micromoles). Due to their high selectivity (highest SI's=50-83) these compounds are of significant interest for further in vivo experiments as well as for further structural optimization and drug development. PMID- 27670101 TI - Direct protein-protein conjugation by genetically introducing bioorthogonal functional groups into proteins. AB - Proteins often function as complex structures in conjunction with other proteins. Because these complex structures are essential for sophisticated functions, developing protein-protein conjugates has gained research interest. In this study, site-specific protein-protein conjugation was performed by genetically incorporating an azide-containing amino acid into one protein and a bicyclononyne (BCN)-containing amino acid into the other. Three to four sites in each of the proteins were tested for conjugation efficiency, and three combinations showed excellent conjugation efficiency. The genetic incorporation of unnatural amino acids (UAAs) is technically simple and produces the mutant protein in high yield. In addition, the conjugation reaction can be conducted by simple mixing, and does not require additional reagents or linker molecules. Therefore, this method may prove very useful for generating protein-protein conjugates and protein complexes of biochemical significance. PMID- 27670102 TI - Magnetite Core-Shell Nanoparticles in Nondestructive Flaw Detection of Polymeric Materials. AB - Nondestructive flaw detection in polymeric materials is important but difficult to achieve. In this research, the application of magnetite nanoparticles (MNPs) in nondestructive flaw detection is studied and realized, to the best of our knowledge, for the first time. Superparamagnetic and highly magnetic (up to 63 emu/g) magnetite core-shell nanoparticles are prepared by grafting bromo-end group-functionalized poly(glycidyl methacrylate) (Br-PGMA) onto surface-modified Fe3O4 NPs. These Fe3O4-PGMA NPs are blended into bisphenol A diglycidylether (BADGE)-based epoxy to form homogeneously distributed magnetic epoxy nanocomposites (MENCs) after curing. The core Fe3O4 of the Fe3O4-PGMA NPs endows the MENCs with magnetic property, which is crucial for nondestructive flaw detection of the materials, while the shell PGMA promotes colloidal stability and prevents NP aggregation during curing. The eddy current testing (ET) technique is first applied to detect flaws in the MENCs. Through the brightness contrast of the ET image, surficial and subsurficial flaws in MENCs can be detected, even for MENCs with low content of Fe3O4-PGMA NPs (1 wt %). The incorporation of Fe3O4 PGMA NPs can be easily extended to other polymer and polymer-based composite systems and opens a new and very promising pathway toward MNP-based nondestructive flaw detection in polymeric materials. PMID- 27670103 TI - Twinning Rates in Isolates. AB - The aim of this study was to investigate the twinning rates (TWRs) in isolates relative to the TWRs in the surrounding populations. It is not uncommon that the TWR shows extreme values (high or low rates) within isolated subpopulations. Starting from the isolated populations of the Aland Islands in Finland (high rates), we enlarged our studies to other isolated subpopulations in other countries: the island of Gotland (high rates), the county of Alvsborg located in the southwestern part of Sweden (low rates), and mountain villages in Norway. In our statistical analyses, we paid special attention to the robustness of the variance formula of the TWR and to alternative confidence intervals for the TWR. Particularly, we show how to obtain the most precise confidence intervals for the twinning rates. These statistical methods are crucial when the extreme TWRs within subpopulations are compared with the TWRs within the general population. One must decide whether the differences are real or caused by random fluctuations within the small isolates. PMID- 27670105 TI - 17. Unionstagung der Schweizerischen Gesellschaften fur Gefasskrankheiten gemeinsam mit der Schweizerischen Gesellschaft fur Ultraschall in der Medizin Sektion Gefasse. PMID- 27670104 TI - Thickness of Actinic Keratosis Does Not Predict Dysplasia Severity or P53 Expression. AB - The severity of dysplasia and expression of p53 in actinic keratosis (AK) is of importance for the transformation to squamous cell carcinoma. It is assumed that it is most important to treat thick AKs as they are believed to be more dysplastic than thin AKs. However, a relation between AK thickness and dysplasia or the expression of p53 has never been demonstrated. The aim of this study was to investigate this possible relation. Sixty-six AKs were included for clinical and histological examination. Prior to performing a punch biopsy, the clinical thickness of each AK was measured objectively using two scale bars with a thickness of 0.5 mm and 1 mm. Subsequently, the thickness of the epidermis, the severity of dysplasia and the expression of p53 were assessed histologically. We found a strong and significant positive correlation between measured clinical thickness of the AKs and the histological thickness of epidermis (p < 0.0001). However, the clinical thickness did not correlate with either the severity of dysplasia (p = 0.7) or the expression of p53 (p = 0.5). In conclusion, thin AKs show the same severity of dysplasia and expression of p53 as thicker AK lesions. Consequently, clinical thickness cannot predict aggressiveness. PMID- 27670106 TI - Structure, Variation, and Co-occurrence of Soil Microbial Communities in Abandoned Sites of a Rare Earth Elements Mine. AB - Mining activity for rare earth elements (REEs) has caused serious environmental pollution, particularly for soil ecosystems. However, the effects of REEs on soil microbiota are still poorly understood. In this study, soils were collected from abandoned sites of a REEs mine, and the structure, diversity, and co-occurrence patterns of soil microbiota were evaluated by Illumina high-throughput sequencing targeting 16S rRNA genes. Although microbiota developed significantly along with the natural restoration, the microbial structure on the site abandoned for 10 years still significantly differed from that on the unmined site. Potential plant growth promoting bacteria (PGPB) were identified by comparing 16S sequences against a self-constructed PGPB database via BLAST, and it was found that siderophore-producing and phosphorus-solubilizing bacteria were more abundant in the studied soils than in reference soils. Canonical correspondence analysis indicated that species richness of plant community was the prime factor affecting microbial structure, followed by limiting nutrients (total carbon and total nitrogen) and REEs content. Further co-occurring network analysis revealed nonrandom assembly patterns of microbiota in the studied soils. These results increase our understanding of microbial variation and assembly pattern during natural restoration in REE contaminated soils. PMID- 27670107 TI - Synthesis and Characterization of Polysubstituted Dibenzopyrenes as Charge Transporting Materials. AB - A new class of benzopyrene-based semiconducting molecules is prepared and characterized. A four-step protocol involving Suzuki coupling and aromatic dehydrogenation reactions renders the new unsymmetrical framework. Introduction of various substituents at the dibenzopyrene framework modulates mainly the optoelectronic properties rather than the packing motif. Single-crystal field effect transistors fabricated from these materials show a mobility ranging from 0.7 to 3.2 cm2/(V s). The highest mobility, 3.2 cm2/(V s), with an on/off ratio of 104-105 was achieved for 11-methoxy-8-(4-methoxyphenyl)dibenzo[a,e]pyrene. PMID- 27670108 TI - A new glycosidic antioxidant from Ranunculus muricatus L. (Ranunculaceae) exhibited lipoxygenasae and xanthine oxidase inhibition properties. AB - Phytochemical investigation of Ranunculus muricatus L. (Ranunculaceae) led to the isolation of a new metabolite named as ranuncoside from the ethyl acetate fraction of the plant. Structure of the novel compound was elucidated through detailed spectroscopic analyses, using UV, IR, 1H, 13C NMR and 2D NMR in combination with EIMS and HR EI-MS techniques. The compound was evaluated for antioxidant activity using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay. Its inhibitory potential was tested against lipoxygenase and xanthine oxidase enzymes. Ranuncoside potently scavenged the DPPH free radicals (IC50 = 56.7 +/- 0.43 MUM) and strongly inhibited the activities of lipoxygenase (IC50 = 63.9 +/- 0.17 MUM) and xanthine oxidase (IC50 = 43.3 +/- 0.22 MUM). PMID- 27670110 TI - Probing the metabolic heterogeneity of live Euglena gracilis with stimulated Raman scattering microscopy. AB - Understanding metabolism in live microalgae is crucial for efficient biomaterial engineering, but conventional methods fail to evaluate heterogeneous populations of motile microalgae due to the labelling requirements and limited imaging speeds. Here, we demonstrate label-free video-rate metabolite imaging of live Euglena gracilis and statistical analysis of intracellular metabolite distributions under different culture conditions. Our approach provides further insights into understanding microalgal heterogeneity, optimizing culture methods and screening mutant microalgae. PMID- 27670109 TI - Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome. AB - Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here, we report culture independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecological analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture and correlated with the intensity of systemic inflammation. Alveolar TNF alpha, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases. PMID- 27670111 TI - Interplay between microbial d-amino acids and host d-amino acid oxidase modifies murine mucosal defence and gut microbiota. AB - L-Amino acids are the building blocks for proteins synthesized in ribosomes in all kingdoms of life, but d-amino acids (d-aa) have important non-ribosome-based functions(1). Mammals synthesize d-Ser and d-Asp, primarily in the central nervous system, where d-Ser is critical for neurotransmission(2). Bacteria synthesize a largely distinct set of d-aa, which become integral components of the cell wall and are also released as free d-aa(3,4). However, the impact of free microbial d-aa on host physiology at the host-microbial interface has not been explored. Here, we show that the mouse intestine is rich in free d-aa that are derived from the microbiota. Furthermore, the microbiota induces production of d-amino acid oxidase (DAO) by intestinal epithelial cells, including goblet cells, which secrete the enzyme into the lumen. Oxidative deamination of intestinal d-aa by DAO, which yields the antimicrobial product H2O2, protects the mucosal surface in the small intestine from the cholera pathogen. DAO also modifies the composition of the microbiota and is associated with microbial induction of intestinal sIgA. Collectively, these results identify d-aa and DAO as previously unrecognized mediators of microbe-host interplay and homeostasis on the epithelial surface of the small intestine. PMID- 27670112 TI - Microbial mercury methylation in Antarctic sea ice. AB - Atmospheric deposition of mercury onto sea ice and circumpolar sea water provides mercury for microbial methylation, and contributes to the bioaccumulation of the potent neurotoxin methylmercury in the marine food web. Little is known about the abiotic and biotic controls on microbial mercury methylation in polar marine systems. However, mercury methylation is known to occur alongside photochemical and microbial mercury reduction and subsequent volatilization. Here, we combine mercury speciation measurements of total and methylated mercury with metagenomic analysis of whole-community microbial DNA from Antarctic snow, brine, sea ice and sea water to elucidate potential microbially mediated mercury methylation and volatilization pathways in polar marine environments. Our results identify the marine microaerophilic bacterium Nitrospina as a potential mercury methylator within sea ice. Anaerobic bacteria known to methylate mercury were notably absent from sea-ice metagenomes. We propose that Antarctic sea ice can harbour a microbial source of methylmercury in the Southern Ocean. PMID- 27670113 TI - The Mouse Intestinal Bacterial Collection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota. AB - Intestinal bacteria influence mammalian physiology, but many types of bacteria are still uncharacterized. Moreover, reference strains of mouse gut bacteria are not easily available, although mouse models are extensively used in medical research. These are major limitations for the investigation of intestinal microbiomes and their interactions with diet and host. It is thus important to study in detail the diversity and functions of gut microbiota members, including those colonizing the mouse intestine. To address these issues, we aimed at establishing the Mouse Intestinal Bacterial Collection (miBC), a public repository of bacterial strains and associated genomes from the mouse gut, and studied host-specificity of colonization and sequence-based relevance of the resource. The collection includes several strains representing novel species, genera and even one family. Genomic analyses showed that certain species are specific to the mouse intestine and that a minimal consortium of 18 strains covered 50-75% of the known functional potential of metagenomes. The present work will sustain future research on microbiota-host interactions in health and disease, as it will facilitate targeted colonization and molecular studies. The resource is available at www.dsmz.de/miBC. PMID- 27670114 TI - Pseudomonas aeruginosa infection augments inflammation through miR-301b repression of c-Myb-mediated immune activation and infiltration. AB - MicroRNAs (miRNAs) play critical roles in various biological processes, including cell proliferation, development and host defence. However, the molecular mechanism for miRNAs in regulating bacterial-induced inflammation remains largely unclear. Here, we report that miR-301b augments pro-inflammatory response during pulmonary infection, and caffeine suppresses the effect of miR-301b and thereby augments respiratory immunity. LPS treatment or Pseudomonas aeruginosa infection induces miR-301b expression via a TLR4/MyD88/NF-kappaB pathway. Importantly, caffeine decreases miR-301b expression through negative regulation of the cAMP/PKA/NF-kappaB axis. Further, c-Myb is identified as a target of miR-301b, which positively modulates anti-inflammatory cytokines IL-4 and TGF-beta1, but negatively regulates pro-inflammatory cytokines MIP-1alpha and IL-17A. Moreover, repression of miR-301b results in increased transcription of c-Myb and elevated levels of neutrophil infiltration, thereby alleviating infectious symptoms in mice. These findings reveal miR-301b as a new controller of inflammatory response by repressing c-Myb function to inhibit the anti-inflammatory response to bacterial infection, representing a novel mechanism for balancing inflammation. PMID- 27670115 TI - Spirochaete flagella hook proteins self-catalyse a lysinoalanine covalent crosslink for motility. AB - Spirochaetes are bacteria responsible for several serious diseases, including Lyme disease (Borrelia burgdorferi), syphilis (Treponema pallidum) and leptospirosis (Leptospira interrogans), and contribute to periodontal diseases (Treponema denticola)(1). These spirochaetes employ an unusual form of flagella based motility necessary for pathogenicity; indeed, spirochaete flagella (periplasmic flagella) reside and rotate within the periplasmic space(2-11). The universal joint or hook that links the rotary motor to the filament is composed of ~120-130 FlgE proteins, which in spirochaetes form an unusually stable, high molecular-weight complex(9,12-17). In other bacteria, the hook can be readily dissociated by treatments such as heat(18). In contrast, spirochaete hooks are resistant to these treatments, and several lines of evidence indicate that the high-molecular-weight complex is the consequence of covalent crosslinking(12,13,17). Here, we show that T. denticola FlgE self-catalyses an interpeptide crosslinking reaction between conserved lysine and cysteine, resulting in the formation of an unusual lysinoalanine adduct that polymerizes the hook subunits. Lysinoalanine crosslinks are not needed for flagellar assembly, but they are required for cell motility and hence infection. The self catalytic nature of FlgE crosslinking has important implications for protein engineering, and its sensitivity to chemical inhibitors provides a new avenue for the development of antimicrobials targeting spirochaetes. PMID- 27670116 TI - NPF motifs in the vaccinia virus protein A36 recruit intersectin-1 to promote Cdc42:N-WASP-mediated viral release from infected cells. AB - During its egress, vaccinia virus transiently recruits AP-2 and clathrin after fusion with the plasma membrane. This recruitment polarizes the viral protein A36 beneath the virus, enhancing actin polymerization and the spread of infection. We now demonstrate that three NPF motifs in the C-terminus of A36 recruit AP-2 and clathrin by interacting directly with the Epsin15 homology domains of Eps15 and intersectin-1. A36 is the first identified viral NPF motif containing protein shown to interact with endocytic machinery. Vaccinia still induces actin tails in the absence of the A36 NPF motifs. Their loss, however, reduces the cell-to-cell spread of vaccinia. This is due to a significant reduction in virus release from infected cells, as the lack of intersectin-1 recruitment leads to a loss of Cdc42 activation, impairing N-WASP-driven Arp2/3-mediated actin polymerization. Our results suggest that initial A36-mediated virus release plays a more important role than A36-driven super-repulsion in promoting the cell-to-cell spread of vaccinia. PMID- 27670117 TI - Rescue of non-human primates from advanced Sudan ebolavirus infection with lipid encapsulated siRNA. AB - Although significant progress has been made in developing therapeutics against Zaire ebolavirus, these therapies do not protect against other Ebola species such as Sudan ebolavirus (SUDV). Here, we describe an RNA interference therapeutic comprising siRNA targeting the SUDV VP35 gene encapsulated in lipid nanoparticle (LNP) technology with increased potency beyond formulations used in TKM-Ebola clinical trials. Twenty-five rhesus monkeys were challenged with a lethal dose of SUDV. Twenty animals received siRNA-LNP beginning at 1, 2, 3, 4 or 5 days post challenge. VP35-targeting siRNA-LNP treatment resulted in up to 100% survival, even when initiated when fever, viraemia and disease signs were evident. Treatment effectively controlled viral replication, mediating up to 4 log10 reductions after dosing. Mirroring clinical findings, a correlation between high viral loads and fatal outcome was observed, emphasizing the importance of stratifying efficacy according to viral load. In summary, strong survival benefit and rapid control of SUDV replication by VP35-targeting LNP confirm its therapeutic potential in combatting this lethal disease. PMID- 27670118 TI - Widespread formation of alternative 3' UTR isoforms via transcription termination in archaea. AB - Transcription termination sets the 3' end boundaries of RNAs and plays key roles in gene regulation. Although termination has been well studied in bacteria, the signals that mediate termination in archaea remain poorly understood. Here, we applied term-seq to comprehensively map RNA 3' termini, with single-base precision, in two phylogenetically distant archaea: Methanosarcina mazei and Sulfolobus acidocaldarius. Comparison of RNA 3' ends across hundreds of genes revealed the sequence composition of transcriptional terminators in each organism, highlighting both common and divergent characteristics between the different archaeal phyla. We find that, in contrast to bacteria, a considerable portion of archaeal genes are controlled by multiple consecutive terminators, generating several alternative 3' untranslated region isoforms for >30% of the genes. These alternative isoforms often present marked length differences, implying that archaea can employ regulation via alternative 3' untranslated regions, similar to eukaryotes. Although most of the terminators are intergenic, we discover numerous cases in which termination of one gene occurs within the coding region of a downstream gene, implying that leaky termination may tune inter-transcript stoichiometry in multi-gene operons. These results provide the first high-throughput maps of transcriptional terminators in archaea and point to an evolutionary path linking bacterial and eukaryal non-coding regulatory strategies. PMID- 27670119 TI - Archaeal physiology: The secrets of termination. PMID- 27670120 TI - Biogeochemistry: Mercury methylation on ice. PMID- 27670121 TI - Culturing: Looking it up in our gut. PMID- 27670122 TI - Ensuring safety in artisanal food microbiology. PMID- 27670123 TI - Combatting antimicrobial resistance globally. PMID- 27670124 TI - Bacterial physiology: The ties that bind. PMID- 27670125 TI - Shooting for the Moon. PMID- 27670127 TI - The distinction of keratoacanthoma from various types of squamous cell carcinoma with crateriform architecture. PMID- 27670126 TI - Light therapies for acne. AB - BACKGROUND: Acne vulgaris is a very common skin problem that presents with blackheads, whiteheads, and inflamed spots. It frequently results in physical scarring and may cause psychological distress. The use of oral and topical treatments can be limited in some people due to ineffectiveness, inconvenience, poor tolerability or side-effects. Some studies have suggested promising results for light therapies. OBJECTIVES: To explore the effects of light treatment of different wavelengths for acne. SEARCH METHODS: We searched the following databases up to September 2015: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched ISI Web of Science and Dissertation Abstracts International (from inception). We also searched five trials registers, and grey literature sources. We checked the reference lists of studies and reviews and consulted study authors and other experts in the field to identify further references to relevant randomised controlled trials (RCTs). We updated these searches in July 2016 but these results have not yet been incorporated into the review. SELECTION CRITERIA: We included RCTs of light for treatment of acne vulgaris, regardless of language or publication status. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 71 studies, randomising a total of 4211 participants.Most studies were small (median 31 participants) and included participants with mild to moderate acne of both sexes and with a mean age of 20 to 30 years. Light interventions differed greatly in wavelength, dose, active substances used in photodynamic therapy (PDT), and comparator interventions (most commonly no treatment, placebo, another light intervention, or various topical treatments). Numbers of light sessions varied from one to 112 (most commonly two to four). Frequency of application varied from twice daily to once monthly.Selection and performance bias were unclear in the majority of studies. Detection bias was unclear for participant-assessed outcomes and low for investigator-assessed outcomes in the majority of studies. Attrition and reporting bias were low in over half of the studies and unclear or high in the rest. Two thirds of studies were industry-sponsored; study authors either reported conflict of interest, or such information was not declared, so we judged the risk of bias as unclear.Comparisons of most interventions for our first primary outcome 'Participant's global assessment of improvement' were not possible due to the variation in the interventions and the way the studies' outcomes were measured. We did not combine the effect estimates but rated the quality of the evidence as very low for the comparison of light therapies, including PDT to placebo, no treatment, topical treatment or other comparators for this outcome. One study which included 266 participants with moderate to severe acne showed little or no difference in effectiveness for this outcome between 20% aminolevulinic acid (ALA)-PDT (activated by blue light) versus vehicle plus blue light (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.04, low-quality evidence). A study (n = 180) of a comparison of ALA-PDT (activated by red light) concentrations showed 20% ALA was no more effective than 15% (RR 1.05, 95% CI 0.96 to 1.15) but better than 10% ALA (RR 1.22, 95% CI 1.05 to 1.42) and 5% ALA (RR 1.47, 95% CI 1.19 to 1.81). The number needed to treat for an additional beneficial outcome (NNTB) was 6 (95% CI 3 to 19) and 4 (95% CI 2 to 6) for the comparison of 20% ALA with 10% and 5% ALA, respectively.For our second primary outcome 'Investigator-assessed changes in lesion counts', we combined three RCTs, with 360 participants with moderate to severe acne and found methyl aminolevulinate (MAL) PDT (activated by red light) was no different to placebo cream plus red light with regard to change in inflamed lesions (ILs) (mean difference (MD) -2.85, 95% CI -7.51 to 1.81), percentage change in ILs (MD 10.09, 95% CI -20.25 to 0.06), change in non-inflamed lesions (NILs) (MD -2.01, 95% CI -7.07 to 3.05), or in percentage change in NILs (MD -8.09, 95% CI -21.51 to 5.32). We assessed the evidence as moderate quality for these outcomes meaning that there is little or no clinical difference between these two interventions for lesion counts.Studies comparing the effects of other interventions were inconsistent or had small samples and high risk of bias. We performed only narrative synthesis for the results of the remaining trials, due to great variation in many aspects of the studies, poor reporting, and failure to obtain necessary data. Several studies compared yellow light to placebo or no treatment, infrared light to no treatment, gold microparticle suspension to vehicle, and clindamycin/benzoyl peroxide combined with pulsed dye laser to clindamycin/benzoyl peroxide alone. There were also several other studies comparing MAL-PDT to light-only treatment, to adapalene and in combination with long-pulsed dye laser to long-pulsed dye laser alone. None of these showed any clinically significant effects.Our third primary outcome was 'Investigator assessed severe adverse effects'. Most studies reported adverse effects, but not adequately with scarring reported as absent, and blistering reported only in studies on intense pulsed light, infrared light and photodynamic therapies. We rated the quality of the evidence as very low, meaning we were uncertain of the adverse effects of the light therapies.Although our primary endpoint was long term outcomes, less than half of the studies performed assessments later than eight weeks after final treatment. Only a few studies assessed outcomes at more than three months after final treatment, and longer-term assessments are mostly not covered in this review. AUTHORS' CONCLUSIONS: High-quality evidence on the use of light therapies for people with acne is lacking. There is low certainty of the usefulness of MAL-PDT (red light) or ALA-PDT (blue light) as standard therapies for people with moderate to severe acne.Carefully planned studies, using standardised outcome measures, comparing the effectiveness of common acne treatments with light therapies would be welcomed, together with adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. PMID- 27670128 TI - Percutaneous Pulmonary Valve Implantation-Associated Ventricular Tachycardia in Congenital Heart Disease. AB - BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) is utilized for dysfunctional right ventricular outflow tracts (RVOT) to relieve obstruction, regurgitation, and RV dysfunction. PPVI has not been reported to induce arrhythmias. This study is the first to report the incidence of ventricular tachycardia (VT) after PPVI. METHODS: This was a retrospective study of all patients who had PPVI at a single institution. All patients were admitted after PPVI for overnight telemetry monitoring. Patients with no prior history of VT and newly detected VT within 24 hours post-PPVI were considered to have VT related to PPVI. RESULTS: In total, 79 patients had PPVI (age 17 +/- 9 years, 66% tetralogy of Fallot/pulmonary atresia). PPVI-related VT was detected in 6 patients (7.5%). These patients had a lower BMI (17.5 +/- 2.0 vs. 23.1 +/- 6.6, P = 0.04). There was no difference in age, native conduit or percutaneous valve size, or change in the minimum diameter of the RVOT from pre- to post-PPVI. In the 6 patients, VT was non-sustained and monomorphic at rates between 120 and 170. Five started on beta-blockers. No patient required surgical explantation of the valve. Over a median follow-up of 2 years, 4 have weaned off medications and all are free of recurrence of VT with normal Holters. CONCLUSIONS: PPVI may be associated with transient VT in the acute peri-procedural period. Patients of smaller size may be more susceptible. All patients were managed conservatively and none of the patients had a recurrence, which is suggestive of a transient phenomenon. PMID- 27670129 TI - Using a meta-ethnographic approach to explore the nature of facilitation and teaching approaches employed in interprofessional education. AB - BACKGROUND: Interprofessional facilitators and teachers are regarded as central to the effective delivery of interprofessional education (IPE). As the IPE literature continues to expand, most studies have focused on reporting learner outcomes, with little attention paid to IPE facilitation. However, a number of studies have recently emerged reporting on this phenomenon. AIM: To present a synthesis of qualitative evidence on the facilitation of IPE, using a meta ethnographic approach. METHODS: Electronic databases and journals were searched for the past 10 years. Of the 2164 abstracts initially found, 94 full papers were reviewed and subsequently 12 papers were included. Teams of two reviewers independently completed each step in the review process. The quality of these papers was assessed using a modified critical appraisal checklist. RESULTS: Seven key concepts embedded in the included studies were synthesized into three main factors which provided an insight into the nature of IPE facilitation. Specifically, the synthesis found that IPE facilitation is influenced by "contextual characteristics"; "facilitator experiences"; and the "use of different facilitation strategies". CONCLUSIONS: IPE facilitation is a complex activity affected by contextual, experiential and pedagogical factors. Further research is needed to explore the effects of these factors on the delivery of IPE. PMID- 27670130 TI - Self-Discrepancy and Eating Disorder Symptoms Across Eating Disorder Diagnostic Groups. AB - This study examined self-discrepancy, a construct of theoretical relevance to eating disorder (ED) psychopathology, across different types of EDs. Individuals with anorexia nervosa (AN; n = 112), bulimia nervosa (BN; n = 72), and binge eating disorder (BED; n = 199) completed semi-structured interviews assessing specific types of self-discrepancies. Results revealed that actual:ideal (A:I) discrepancy was positively associated with AN, actual:ought (A:O) discrepancy was positively associated with BN and BED, and self-discrepancies did not differentiate BN from BED. Across diagnoses, A:O discrepancy was positively associated with severity of purging, binge eating, and global ED psychopathology. Further, there were significant interactions between diagnosis and A:O discrepancy for global ED psychopathology and between diagnosis and A:I discrepancy for binge eating and driven exercise. These results support the importance of self-discrepancy as a potential causal and maintenance variable in EDs that differentiates among different types of EDs and symptom severity. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 27670131 TI - Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis. AB - Cell migration is an essential process in organism development and physiological maintenance. Although current methods permit accurate comparisons of the effects of molecular manipulations and drug applications on cell motility, effects of alterations in subcellular activities on motility cannot be fully elucidated from those methods. Here, we develop a strategy termed cell-nuclear (CN) correlation to parameterize represented dynamic subcellular activities and to quantify their contributions in mesenchymal-like migration. Based on the biophysical meaning of the CN correlation, we propose a cell migration potential index (CMPI) to measure cell motility. When the effectiveness of CMPI was evaluated with respect to one of the most popular cell migration analysis methods, Persistent Random Walk, we found that the cell motility estimates among six cell lines used in this study were highly consistent between these two approaches. Further evaluations indicated that CMPI can be determined using a shorter time period and smaller cell sample size, and it possesses excellent reliability and applicability, even in the presence of a wide range of noise, as might be generated from individual imaging acquisition systems. The novel approach outlined here introduces a robust strategy through an analysis of subcellular locomotion activities for single cell migration assessment. PMID- 27670132 TI - Productive performance of weanling piglets was improved by administration of a mixture of bacteriophages, targeted to control Coliforms and Clostridium spp. shedding in a challenging environment. AB - This study was conducted to investigate the effects of bacteriophages in different environments on growth performance, digestibility, ileal and caecal microbiota, gut morphology and immunity of weanling pigs. Two hundred piglets were randomly assigned to four treatment groups with five replicate pens with 10 pigs per pen. A 2 * 2 factorial arrangement of treatments was used to investigate the response of weanling pigs to supplemental bacteriophages (0 and 1.0 g/kg of diet) in contaminated or hygienic environments. Bacteriophages supplementation did not affect average daily gain (ADG), average daily feed intake (ADFI) and gain:feed in phases I and III; however, there was a significant improvement in ADG and gain:feed in phase II. The supplementation of bacteriophages increased the overall gain:feed of pigs. The overall result showed a greater ADG and ADFI in hygienic room. There were reductions in population of both ileal (p < 0.05) and caecal (p < 0.01) Clostridium spp. and ileal coliforms (p < 0.01) with the inclusion of bacteriophages in the diet. Bacteriophages increased ileal Lactobacillus and caecal Bifidobacterium and tended to increase ileal Bifidobacterium (p = 0.08). Contaminated environment decreased ileal Lactobacillus and caecal Bifidobacterium and tended to increase ileal Clostridium (p = 0.08) and coliforms (p = 0.08). Total anaerobic bacteria was tended to decrease (p = 0.06) in contaminated environment. Jejunal villus height increased in pigs received bacteriophages, but they did not affect other morphological items. The interaction between bacteriophages and environment tended to be significant (p = 0.06) for ileal villus height and ileal villus height to crypt depth ratio. The overall faecal score was significantly greater in hygienic environment and bacteriophages groups. The present findings indicate that there is an interactive effect on feed efficiency between bacteriophages and contaminated environment. In addition, bacteriophages improve jejunum morphology, and intestinal microbiota of pigs. PMID- 27670133 TI - Selexipag in Pulmonary Arterial Hypertension: Most Updated Evidence From Recent Preclinical and Clinical Studies. AB - Pulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI2 ) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice-daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6-minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all-cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT 1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH. PMID- 27670135 TI - Role of femoral anterior Bow in cephalomedullary nailing: finite element analysis and New index estimation. AB - BACKGROUND: Cephalomedullary Nail (CMN) is seen as the mainstay of internal fixation in femoral fractures. The purpose of the study was to present an accurate calculation method by simulating diverse anterior bow femoral models with finite element software. We hypothesized that anterior cortical penetration in distal femur would occur in patients whose femoral anterior bow was identified as too large for nailing by preoperative measurement of contralateral X-ray. METHODS: A 31-year healthy male was selected for building 3D bone model through computed tomography (CT) scan of right femoral femur. In Creo Parametric 2.0, the middle section of the femur was twisted gradually to simulate the different femoral anterior bow. Ratio of chord height and half chord length, belonging to the middle section arc, was defined as the tangent value of the femoral anterior bow. The value corresponding to the penetration of the CMN at the distal femur was regarded as critical value, showing the extreme curvature for CMN. RESULT: Three types of right femoral CMNs (o10, 11, 12 mm * 350 mm; Smith-Nephew Co.) were involved in our study. The CMN passed through distal femur anterior cortex when the tangent value of the femoral anterior bow are 0.140185, 0.133073, 0.092415 respectively, and the corresponding central angle are 21.72 degrees , 20.92 degrees , 16.32 degrees . CONCLUSIONS: The tangent value of the femoral anterior bow would be a precise calculated method, that eliminate the deviation by description of ratio rather than length of radius. An application of this preoperative evaluation can aid surgeons during surgical planning. TRIAL REGISTRATION: Retrospectively registered. PMID- 27670136 TI - The contribution of databases to the results of systematic reviews: a cross sectional study. AB - BACKGROUND: One of the best sources for high quality information about healthcare interventions is a systematic review. A well-conducted systematic review includes a comprehensive literature search. There is limited empiric evidence to guide the extent of searching, in particular the number of electronic databases that should be searched. We conducted a cross-sectional quantitative analysis to examine the potential impact of selective database searching on results of meta-analyses. METHODS: Our sample included systematic reviews (SRs) with at least one meta analysis from three Cochrane Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID), Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes included: 1) proportion of relevant studies indexed in each of 10 databases; and 2) changes in results and statistical significance of primary meta-analysis for studies identified in Medline only and in Medline plus each of the other databases. RESULTS: Due to variation across topics, we present results by group (ARI n = 57, ID n = 38, DPLP n = 34). For ARI, identification of relevant studies was highest for Medline (85 %) and Embase (80 %). Restricting meta-analyses to trials that appeared in Medline + Embase yielded fewest changes in statistical significance: 53/55 meta-analyses showed no change. Point estimates changed in 12 cases; in 7 the change was less than 20 %. For ID, yield was highest for Medline (92 %), Embase (81 %), and BIOSIS (67 %). Restricting meta-analyses to trials that appeared in Medline + BIOSIS yielded fewest changes with 1 meta-analysis changing in statistical significance. Point estimates changed in 8 of 31 meta-analyses; change less than 20 % in all cases. For DPLP, identification of relevant studies was highest for Medline (75 %) and Embase (62 %). Restricting meta-analyses to trials that appeared in Medline + PsycINFO resulted in only one change in significance. Point estimates changed for 13 of 33 meta-analyses; less than 20 % in 9 cases. CONCLUSIONS: Majority of relevant studies can be found within a limited number of databases. Results of meta analyses based on the majority of studies did not differ in most cases. There were very few cases of changes in statistical significance. Effect estimates changed in a minority of meta-analyses but in most the change was small. Results did not change in a systematic manner (i.e., regularly over- or underestimating treatment effects), suggesting that selective searching may not introduce bias in terms of effect estimates. PMID- 27670134 TI - Structural Considerations on the Use of Endo-Xylanases for the Production of prebiotic Xylooligosaccharides from Biomass. AB - Xylooligosaccharides (XOS) have gained increased interest as prebiotics during the last years. XOS and arabinoxylooligosaccharides (AXOS) can be produced from major fractions of biomass including agricultural by-products and other low cost raw materials. Endo-xylanases are key enzymes for the production of (A)XOS from xylan. As the xylan structure is broadly diverse due to different substitutions, diverse endo-xylanases have evolved for its degradation. In this review structural and functional aspects are discussed, focusing on the potential applications of endo-xylanases in the production of differently substituted (A)XOS as emerging prebiotics, as well as their implication in the processing of the raw materials. Endo-xylanases are found in at least eight different glycoside hydrolase families (GH), and can either have a retaining or an inverting catalytic mechanism. To date, it is mainly retaining endo-xylanases that are used in applications to produce (A)XOS. Enzymes from these GH-families (mainly GH10 and GH11, and the more recently investigated GH30) are taken as prototypes to discuss substrate preferences and main products obtained. Finally, the need of new and accessory enzymes (new specificities from new families or sources) to increase the yield of different types of (A)XOS is discussed, along with in vitro tests of produced oligosaccharides and production of enzymes in GRAS organisms to facilitate use in functional food manufacturing. PMID- 27670137 TI - Comparison of sodium content of meals served by independent takeaways using standard versus reduced holed salt shakers: cross-sectional study. AB - BACKGROUND: Takeaway food has a relatively poor nutritional profile. Providing takeaway outlets with reduced-holed salt shakers is one method thought to reduce salt use in takeaways, but effects have not been formally tested. We aimed to determine if there was a difference in sodium content of standard fish and chip meals served by Fish & Chip Shops that use standard (17 holes) versus reduced holed (5 holes) salt shakers, taking advantage of natural variations in salt shakers used. METHODS: We conducted a cross-sectional study of all Fish & Chip Shops in two local government areas (n = 65), where servers added salt to meals as standard practice, and salt shaker used could be identified (n = 61). Standard fish and chip meals were purchased from each shop by incognito researchers and the purchase price and type of salt shaker used noted. Sodium content of full meals and their component parts (fish, chips, and fish batter) was determined using flame photometry. Differences in absolute and relative sodium content of meals and component parts between shops using reduced-holed versus standard salt shakers were compared using linear regression before and after adjustment for purchase price and area. RESULTS: Reduced-holed salt shakers were used in 29 of 61 (47.5 %) included shops. There was no difference in absolute sodium content of meals purchased from shops using standard versus reduced-holed shakers (mean = 1147 mg [equivalent to 2.9 g salt]; SD = 424 mg; p > 0.05). Relative sodium content was significantly lower in meals from shops using reduced-holed (mean = 142.5 mg/100 g [equivalent to 0.4 g salt/100 g]; SD = 39.0 mg/100 g) versus standard shakers (mean = 182.0 mg/100 g; [equivalent to 0.5 g salt/100 g]; SD = 68.3 mg/100 g; p = 0.008). This was driven by differences in the sodium content of chips and was extinguished by adjustment for purchase price and area. Price was inversely associated with relative sodium content (p < 0.05). CONCLUSIONS: Using reduced-holed salt shakers in Fish & Chip Shops is associated with lower relative sodium content of fish and chip meals. This is driven by differences in sodium content of chips, making our results relevant to the wide range of takeaways serving chips. Shops serving higher priced meals, which may reflect a more affluent customer base, may be more likely to use reduced-holed shakers. PMID- 27670138 TI - The ABBA study - approach bias modification in bulimia nervosa and binge eating disorder: study protocol for a randomised controlled trial. AB - BACKGROUND: The core symptoms of bulimia nervosa (BN) and binge eating disorder (BED) are recurrent episodes of binge eating. Despite negative psychological and physical consequences, BN/BED patients show uncontrollable approach tendencies towards food. This cognitive bias occurs at an early stage of information processing. Cognitive bias modification (CBM) directly targets such biases and has been shown to be effective in treating several mental disorders. In alcohol addiction, automatic action tendencies towards alcohol cues and relapse rates were successfully reduced by a specific form of CBM, termed approach bias modification. Based on these findings and data from a proof-of-concept study in people with high levels of food craving, CBM is considered a promising new treatment approach for BN/BED. Given the similarities between BN/BED and addictive disorders, the rationale for using approach bias modification appears to be particularly strong. The aim of the present study is to examine whether, compared to a sham training, computerised approach bias modification (10 sessions) can reduce binge-eating episodes in BN/BED patients from pre-treatment to follow-up. Additionally, we will investigate whether this CBM programme also reduces global eating disorder psychopathology, trait and cue-elicited food craving, food intake as well as approach and attentional bias towards visual food cues. Treatment acceptance will be determined by attrition rates and responses on a feedback form. METHODS: This is a double-blind, randomised, placebo-controlled, parallel-group superiority trial with two parallel arms. A total of 54 BN/BED patients will be recruited. Approach bias towards food will be retrained by a computer task adopting an implicit learning paradigm. Patients in the control condition (sham) will conduct a similar task but will not be trained to avoid food cues. Methods against bias include public registration, randomisation by a central study office, standardisation of the treatments and blinding of assessors. Furthermore, the session number and duration will be equivalent in the two conditions. DISCUSSION: This is the first registered randomised controlled trial of approach bias modification in a clinical BN/BED sample. Results from this study will provide an indication of the efficacy of approach bias modification training for BN/BED and the potential mechanisms of action underlying this treatment. TRIAL REGISTRATION: DRKS00010231 (retrospectively registered on 24 March 2016; first version). PMID- 27670139 TI - Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword. AB - Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable. Although cancer cells appear to be advantageously defective in some aspects of checkpoint physiology, recent acquisitions on the biochemical mechanisms of the various checkpoints are offering new therapeutic approaches against cancer. Indeed, chemical manipulation of these mechanisms is providing new therapeutic strategies and tools to increase the killing efficacy of major cancer therapeutics as well as to directly promote cancer cell death. In this review we summarize developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy. PMID- 27670141 TI - The Interplay between a Multifunctional Dehydratase Domain and a C Methyltransferase Effects Olefin Shift in Ambruticin Biosynthesis. AB - The olefin shift is an important modification during polyketide biosynthesis. Particularly for type I cis-AT PKS, little information has been gained on the enzymatic mechanisms involved. We present our in vitro investigations on the olefin shift occurring during ambruticin biosynthesis. The unique, multifunctional domain AmbDH4 catalyzes consecutive dehydration, epimerization, and enoyl isomerization. The resulting 3-enethioate is removed from the equilibrium by alpha-methylation catalyzed by the highly specific C methyltransferase AmbM. This thermodynamically unfavorable overall process is enabled by the high, concerted substrate specificity of the involved enzymes. AmbDH4 shows close relationship to DH domains and initial mechanistic studies suggest that the olefin shift occurs via a similar proton-shuttling mechanism as previously described for EI domains from trans-AT-PKS. PMID- 27670140 TI - Quantitative chemical exchange saturation transfer MRI of intervertebral disc in a porcine model. AB - PURPOSE: Previous studies have associated low pH in intervertebral discs (IVDs) with discogenic back pain. The purpose of this study was to determine whether quantitative CEST (qCEST) MRI can be used to detect pH changes in IVDs in vivo. METHODS: The exchange rate ksw between glycosaminoglycan (GAG) protons and water protons was determined from qCEST analysis. Its dependence on pH value was investigated in GAG phantoms with varying pH and concentrations. The relationship between ksw and pH was studied further in vivo in a porcine model on a 3T MR scanner and validated using a pH meter. Sodium lactate was injected into the IVDs to induce various pH values within the discs ranging from 5 to 7. RESULTS: Phantom and animal results revealed that ksw measured using qCEST MRI is highly correlated with pH level. In the animal studies, the relationship can be described as ksw =9.2 * 106 * 10-pH + 196.9, R2 = 0.7883. CONCLUSION: The exchange rate between GAG and water protons determined from qCEST MRI is closely correlated with pH value. This technique has the potential to noninvasively measure pH in the IVDs of patients with discogenic pain. Magn Reson Med 76:1677 1683, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27670142 TI - StreetWise: developing a serious game to support forensic mental health service users' preparation for discharge: a feasibility study. AB - : WHAT IS KNOWN ON THE SUBJECT?: Serious gaming can support learning and development. The use of serious games for skills development and the rehearsal of the management of events that cannot be replicated in real life is well established. Few serious games have been used in mental health services, and none in forensic mental health care. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: How a serious game may be coproduced by forensic mental health service users and game developers The acceptability of the therapeutic use of serious gaming by forensic mental health service users and providers. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Computer games may be used by practitioners in their therapeutic work with forensic mental health service users. Mental health nurses to use serious games to creatively and safely bridge the gap for service users between receiving care in controlled environments and living more independent in the community. ABSTRACT: Introduction Assessment of users' skills and confidence to safely respond to risky community-based situations underpins discharge planning. Serious games have been used for skills development, and this study trialled their use in forensic mental health services. Aim The aim was to develop and test the acceptability and usability of an innovative serious game to support forensic mental health service users' preparation for discharge. Method A prototype serious game was developed by service users and researchers. Acceptability and usability testing was undertaken and service providers interviewed about the acceptability of serious gaming for forensic mental health services. Result A prototype game was produced and successfully trialled by service users. However, both service users and providers identified that work needed to be done to develop and test a game with greater complexity. Discussion The acceptability and usability of using serious games to support service users to develop skills needed for successful discharge was demonstrated. Implications for practice Mental health practitioners may use gaming to support their practice and work innovatively with other professions such as game developers to create new ways of working in forensic mental health services. PMID- 27670143 TI - Pancreatic neuroendocrine microadenomatosis: A case report of cytology and histology correlation. AB - Pancreatic neuroendocrine neoplasia is categorized by grade, size, and functional status. Neuroendocrine microadenoma (NEMA) is defined as a neuroendocrine tumor (NET) that measures less than 0.5 cm in diameter. Multiple NEMAs are termed neuroendocrine adenomatosis (NEMAtosis). The surgical pathology and clinical aspects of pancreatic NEMAtosis have been reported, but there has been no report regarding EUS-FNA cytology of NEMAtosis. We report a case of NEMAtosis with cytologic correlation and illustrate the diagnostic challenges and potential pitfalls. The pre-operative cytology can be problematic. The main differential diagnosis of the EUS-FNA specimen includes NET, normal pancreas, and islet cell hyperplasia/aggregation associated with chronic pancreatitis. The helpful cytopathologic feature of NEMAtosis is the presence of two intermingled populations of loosely-cohesive neuroendocrine cell clusters and tight acinar cell groups arranged in microacinar and/or grape-like structures. Although neuroendocrine cells and acinar cells possess different cytomorphology, the distinction is not always straightforward because both types of cells are small and cytologically bland. Cytologic assessment of both architecture and individual cell morphology is imperative to avoid interpretation error and further guide appropriate clinical management. Diagn. Cytopathol. 2017;45:143-147. (c) 2016 Wiley Periodicals, Inc. PMID- 27670144 TI - Evaluation of renal oxygenation change under the influence of carbogen breathing using a dynamic R2 , R2 ' and R2 * quantification approach. AB - The purpose of this study is to demonstrate the feasibility of dynamic renal R2 /R2 '/R2 * measurements based on a method, denoted psMASE-ME, in which a periodic 180 degrees pulse-shifting multi-echo asymmetric spin echo (psMASE) sequence, combined with a moving estimation (ME) strategy, is adopted. Following approval by the institutional animal care and use committee, a block design of respiratory challenge with interleaved air and carbogen (97% O2 , 3% CO2 ) breathing was employed in nine rabbits. Parametrical R2 /R2 '/R2 * maps were computed and average R2 /R2 '/R2 * values were measured in regions of interest in the renal medulla and cortex. Bland-Altman plots showed good agreement between the proposed method and reference standards of multi-echo spin echo and multi-echo gradient echo sequences. Renal R2 , R2 ' and R2 * decreased significantly from 16.2 +/- 4.4 s-1 , 9.8 +/- 5.2 s-1 and 25.9 +/- 5.0 s-1 to 14.9 +/- 4.4 s-1 (p < 0.05), 8.5 +/- 4.1 s-1 (p < 0.05) and 23.4 +/- 4.8 s-1 (p < 0.05) in the cortex when switching the gas mixture from room air to carbogen. In the renal medulla, R2 , R2 ' and R2 * also decreased significantly from 12.9 +/- 4.7 s-1 , 15.1 +/- 5.8 s 1 and 27.9 +/- 5.3 s-1 to 11.8 +/- 4.5 s-1 (p < 0.05), 14.2 +/- 4.2 s-1 (p < 0.05) and 25.8 +/- 5.1 s-1 (p < 0.05). No statistically significant differences in relative R2 , R2 ' and R2 * changes were observed between the cortex and medulla (p = 0.72 for R2 , p = 0.39 for R2 ' and p = 0.61 for R2 *). The psMASE ME method for dynamic renal R2 /R2 '/R2 * measurements, together with the respiratory challenge, has potential use in the evaluation of renal oxygenation in many renal diseases. PMID- 27670145 TI - Zofenopril exerts a cardiovascular protective effect on rats infused with angiotensin II beyond angiotensin-converting enzyme inhibition. AB - OBJECTIVES: Elevated levels of angiotensin II are implicated in the hypertensive pathophysiological process. Zofenopril has a sulphydryl group which gives it antioxidant properties. The aim of this study was to investigate its beneficial effects beyond angiotensin-converting enzyme (ACE) inhibition using angiotensin II-infused rats as hypertension model. METHODS: Zofenopril was added in drinking water. Systolic blood pressure was assessed by the tail-cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. An estimate of the cardiac collagen was performed by measuring the content of hydroxyproline. Vascular reactivity was evaluated on aortic rings and isolated perfused kidney, and vascular structure in thoracic aorta was studied. Superoxide anion generation was quantified in aorta by lucigenin-enhanced chemiluminescence. KEY FINDINGS: Zofenopril partially prevented the increase in systolic blood pressure and cardiac hypertrophy induced by angiotensin II and avoided the increase in collagen deposition. The treatment improved vasorelaxing responses, reversed the vascular remodelling and abolished the effects of angiotensin II on the production of .O2-. It is worth to mention that all these results are observed even with high levels of plasma angiotensin. CONCLUSION: Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II. PMID- 27670146 TI - Three cases of spontaneous lumbar artery rupture in hemodialysis patients. AB - We encountered three cases of retroperitoneal hematoma caused by spontaneous lumbar artery rupture, a rare vascular complication. At the time of retroperitoneal hematoma, two patients were on anticoagulant/antiplatelet therapy. One patient was not taking any anticoagulant/antiplatelet agents but was receiving hemodialysis treatment with heparin. Lumbar artery rupture was successfully controlled by transcatheter arterial embolization in all patients, but one patient developed multiple organ failure and died. We suggest that spontaneous lumbar artery rupture may occur in patients being treated with maintenance hemodialysis or anticoagulant/antiplatelet therapy. Therefore, clinicians should suspect lumbar artery rupture in patients with unstable vital signs and rapid onset of anemia because early diagnosis and appropriate intervention are necessary to decrease the risks of morbidity and mortality. PMID- 27670147 TI - Procedural and shunt-related complications and mortality of the transjugular intrahepatic portosystemic shunt (TIPSS). AB - BACKGROUND: The implantation of a transjugular intrahepatic portosystemic shunt (TIPSS) is a complex angiographic procedure performed in patients with end-stage liver disease. Numerous case reports and narrative reviews have been published so far; however, studies systematically investigating procedural and shunt-related complications are lacking. AIM: To systematically investigate complications and mortality occurring during the index hospital stay and the early (4-week) period after TIPSS implantation. METHODS: The study includes 389 patients who received a TIPSS implantation between 2004 and 2014. Data were obtained from the clinical records and technical reports of the TIPSS implantation. RESULTS: During the index hospital stay, procedure-related complications occurred in 42 patients (10.8%) with intraperitoneal bleeding in 8 patients (2.1%) and infections in 14 patients (3.6%). Shunt- and disease-related complications consisted of hepatic encephalopathy (1-year incidence 29%), non-procedural infections (8.7%) and acute hepatic decompensation (4.1%). Nine patients (2.3%) died during the index hospital stay from procedure-related (two patients, 0.5%), shunt-related (four patients, 1%) or disease-related causes (three patients, 0.8%). 23 patients (5.9%) died during 4 weeks after TIPSS implantation. The 1-year probability of survival was 67.7% and was negatively associated with severe hepatic encephalopathy and acute hepatic decompensation. CONCLUSIONS: Except hepatic encephalopathy, severe procedure- and shunt-related complications are rare and early mortality is low. PMID- 27670148 TI - Keeping all options open: Parents' approaches to advance care planning. AB - BACKGROUND: Early engagement in advance care planning (ACP) is seen as fundamental for ensuring the highest standard of care for children and young people with a life-limiting condition (LLC). However, most families have little knowledge or experience of ACP. OBJECTIVE: To investigate how parents of children and young people with LLCs approach and experience ACP. METHODS: Open-ended, semi structured interviews were conducted with parents of 18 children; nine children who were currently receiving palliative care services, and nine children who had received palliative care and died. Verbatim transcripts of audiotaped interviews were analysed following principles of grounded theory while acknowledging the use of deductive strategies, taking account of both the child's condition, and the timing and nature of decisions made. RESULTS: Parents reported having discussions and making decisions about the place of care, place of death and the limitation of treatment. Most decisions were made relatively late in the illness and by parents who wished to keep their options open. Parents reported different levels of involvement in a range of decisions; many wished to be involved in decision making but did not always feel able to do so. DISCUSSION: This study highlights that parents' approaches to decision making vary by the type of decision required. Their views may change over time, and it is important to allow them to keep their options open. We recommend that clinicians have regular discussions over the course of the illness in an effort to understand parents' approaches to particular decisions rather than to drive to closure prematurely. PMID- 27670149 TI - Value of Measuring Bone Microarchitecture in Fracture Discrimination in Older Women with Recent Hip Fracture: A Case-control Study with HR-pQCT. AB - We aimed to determine whether loss of volumetric bone mineral density (vBMD) and deterioration of microarchitecture imaged by high-resolution peripheral quantitative computed tomography at the distal radius/tibia provided additional information in fracture discrimination in postmenopausal women with recent hip fracture. This case-control study involved 24 postmenopausal Chinese women with unilateral femoral neck fracture (average [SD] age: 79.6[5.6]) and 24 age-matched women without any history of fracture. Each SD decrease in T-score at femoral neck (FN) was associated with a higher fracture risk (odds ratio: 6.905, p = 0.001). At the distal radius, fracture women had significantly lower total vBMD ( 17.5%), fewer (-20.3%) and more unevenly spaced (81.4%) trabeculae, and thinner cortices (-14.0%) (all p < 0.05). At the distal tibia, vBMD was on average -4.7% (cortical) to -25.4% (total) lower, trabecular microarchitecture was on average 19.8% (number) to 102% (inhomogeneity) inferior, cortices were thinner (-21.1%) and more porous (18.2%) (all p < 0.05). Adding parameters of vBMD and microarchitecture in multivariate models did not offer additional discriminative capacity of fracture status compared with using T-score at FN. In old postmenopausal women with already excessive loss of bone mass, measuring bone microarchitecture may provide limited added value to improve identification of risk of femoral neck fracture. PMID- 27670150 TI - In vitro investigation of intestinal transport mechanism of silicon, supplied as orthosilicic acid-vanillin complex. AB - SCOPE: Silicon (Si) is one of the most abundant trace elements in the body. Although pharmacokinetics data described its absorption from the diet and its body excretion, the mechanisms involved in the uptake and transport of Si across the gut wall have not been established. METHODS AND RESULTS: Caco-2 cells were used as a well-accepted in vitro model of the human intestinal epithelium to investigate the transport, across the intestinal barrier in both the absorption and excretion directions, of Si supplied as orthosilicic acid stabilized by vanillin complex (OSA-VC). The transport of this species was found proportional to the initial concentration and to the duration of incubation, with absorption and excretion mean rates similar to those of Lucifer yellow, a marker of paracellular diffusion, and increasing in the presence of EGTA, a chelator of divalents cations including calcium. A cellular accumulation of Si, polarized from the apical side of cells, was furthermore detected. CONCLUSION: These results provide evidence that Si, ingested as a food supplement containing OSA VC, crosses the intestinal mucosa by passive diffusion via the paracellular pathway through the intercellular tight junctions and accumulates intracellularly, probably by an uptake mechanism of facilitated diffusion. This study can help to further understand the kinetic of absorption of Si. PMID- 27670151 TI - Effectiveness and Cost Efficiency of Different Surveillance Components for Proving Freedom and Early Detection of Disease: Bluetongue Serotype 8 in Cattle as Case Study for Belgium, France and the Netherlands. AB - Quick detection and recovery of country's freedom status remain a constant challenge in animal health surveillance. The efficacy and cost efficiency of different surveillance components in proving the absence of infection or (early) detection of bluetongue serotype 8 in cattle populations within different countries (the Netherlands, France, Belgium) using surveillance data from years 2006 and 2007 were investigated using an adapted scenario tree model approach. First, surveillance components (sentinel, yearly cross-sectional and passive clinical reporting) within each country were evaluated in terms of efficacy for substantiating freedom of infection. Yearly cross-sectional survey and passive clinical reporting performed well within each country with sensitivity of detection values ranging around 0.99. The sentinel component had a sensitivity of detection around 0.7. Secondly, how effective the components were for (early) detection of bluetongue serotype 8 and whether syndromic surveillance on reproductive performance, milk production and mortality data available from the Netherlands and Belgium could be of added value were evaluated. Epidemic curves were used to estimate the timeliness of detection. Sensitivity analysis revealed that expected within-herd prevalence and number of herds processed were the most influential parameters for proving freedom and early detection. Looking at the assumed direct costs, although total costs were low for sentinel and passive clinical surveillance components, passive clinical surveillance together with syndromic surveillance (based on reproductive performance data) turned out most cost-efficient for the detection of bluetongue serotype 8. To conclude, for emerging or re-emerging vectorborne disease that behaves such as bluetongue serotype 8, it is recommended to use passive clinical and syndromic surveillance as early detection systems for maximum cost efficiency and sensitivity. Once an infection is detected and eradicated, cross-sectional screening for substantiating freedom of infection and sentinel for monitoring the disease evolution are recommended. PMID- 27670152 TI - Hazard identification of exhausts from gasoline-ethanol fuel blends using a multi cellular human lung model. AB - Ethanol can be produced from biomass and as such is renewable, unlike petroleum based fuel. Almost all gasoline cars can drive with fuel containing 10% ethanol (E10), flex-fuel cars can even use 85% ethanol (E85). Brazil and the USA already include 10-27% ethanol in their standard fuel by law. Most health effect studies on car emissions are however performed with diesel exhausts, and only few data exists for other fuels. In this work we investigated possible toxic effects of exhaust aerosols from ethanol-gasoline blends using a multi-cellular model of the human lung. A flex-fuel passenger car was driven on a chassis dynamometer and fueled with E10, E85, or pure gasoline (E0). Exhausts obtained from a steady state cycle were directly applied for 6h at a dilution of 1:10 onto a multi cellular human lung model mimicking the bronchial compartment composed of human bronchial cells (16HBE14o-), supplemented with human monocyte-derived dendritic cells and monocyte-derived macrophages, cultured at the air-liquid interface. Biological endpoints were assessed after 6h post incubation and included cytotoxicity, pro-inflammation, oxidative stress, and DNA damage. Filtered air was applied to control cells in parallel to the different exhausts; for comparison an exposure to diesel exhaust was also included in the study. No differences were measured for the volatile compounds, i.e. CO, NOx, and T.HC for the different ethanol supplemented exhausts. Average particle number were 6*102 #/cm3 (E0), 1*105 #/cm3 (E10), 3*103 #/cm3 (E85), and 2.8*106 #/cm3 (diesel). In ethanol-gasoline exposure conditions no cytotoxicity and no morphological changes were observed in the lung cell cultures, in addition no oxidative stress - as analyzed with the glutathione assay - was measured. Gene expression analysis also shows no induction in any of the tested genes, including mRNA levels of genes related to oxidative stress and pro-inflammation, as well as indoleamine 2,3 dioxygenase 1 (IDO-1), transcription factor NFE2-related factor 2 (NFE2L2), and NAD(P)H dehydrogenase [quinone] 1 (NQO1). Finally, no DNA damage was observed with the OxyDNA assay. On the other hand, cell death, oxidative stress, as well as an increase in pro-inflammatory cytokines was observed for cells exposed to diesel exhaust, confirming the results of other studies and the applicability of our exposure system. In conclusion, the tested exhausts from a flex-fuel gasoline vehicle using different ethanol-gasoline blends did not induce adverse cell responses in this acute exposure. So far ethanol-gasoline blends can promptly be used, though further studies, e.g. chronic and in vivo studies, are needed. PMID- 27670153 TI - Extending knowledge of the public awareness of aphasia in the Balkans: Serbia and Montenegro. AB - PURPOSE: Public awareness of aphasia has been surveyed in a number of countries revealing that it is universally low. We report results of surveys in the Balkan countries Serbia and Montenegro and compare results with data from Croatia and Slovenia. METHODS: Convenience surveys of the general public were conducted in public places like shopping centers/malls and parks in Serbia (N = 400) and Montenegro (N = 500) using an adapted version of the public awareness of aphasia survey questionnaire. Respondents were asked whether they have heard of aphasia and tested with questions about aphasia. Information on gender, age, occupation and education was recorded. OUTCOMES: Twelve percent (Serbia) and 11% (Montenegro) had heard of aphasia, but just 4% (Serbia) and 3.2% (Montenegro) had a basic knowledge of aphasia. Age, gender and occupation interacted variably with awareness. Between 16% (Slovenia) and 60% (Croatia) said they had heard of aphasia (10.5% overall mean for the four countries) and basic knowledge of aphasia across the four countries ranged between 3.2 and 7%. CONCLUSIONS: Levels of awareness of aphasia in the Balkans are low and variably associated with age, gender, socio-economic and educational levels. Respondents with some knowledge of aphasia gained it through personal or professional interaction with aphasia or the media. The data provide a basis for awareness raising in Balkan countries to reduce stigmatization, improve community access and understanding. Implications for rehabilitation Awareness of aphasia is low universally, even among healthcare workers. Low public awareness of a condition, like aphasia, results in under funded research and service provision. In order to raise public awareness of aphasia we need to know how many members of the general public know about it. Improvements in public awareness could positively affect funding, the quality of services, and the public understanding and acceptance of individuals with aphasia in the community. Improving awareness of aphasia in those who come into contact with aphasic people, like healthcare workers, could significantly improve the healthcare experience of people with aphasia and their families. PMID- 27670154 TI - Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants. AB - AIM: There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. METHODS: This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. RESULTS: Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). CONCLUSION: Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study. PMID- 27670155 TI - Mandibulofacial dysostosis with microcephaly: A case presenting with seizures. AB - We report a case of mandibulofacial dysostosis with microcephaly presenting with seizures. The proband, a 6-year-old Korean boy, had microcephaly, malar and mandibular hypoplasia, and deafness. He showed developmental delay and had suffered recurrent seizures beginning at 21months of age. Electroencephalography revealed occasional spike discharges from the right frontal area. Head magnetic resonance imaging revealed dilatation of the lateral ventricles and a small frontal lobe volume. Whole exome sequencing revealed a de novo frame shift mutation, c.2698_2701 del, of EFTUD2. The epileptic focus was consistent with the reduced frontal lobe volume on head magnetic resonance imaging. Seizures are thus a main feature of mandibulofacial dysostosis with microcephaly, which results from an embryonic development defect due to the EFTUD2 mutation. PMID- 27670156 TI - Complex Network Clustering by a Multi-objective Evolutionary Algorithm Based on Decomposition and Membrane Structure. AB - The field of complex network clustering is gaining considerable attention in recent years. In this study, a multi-objective evolutionary algorithm based on membranes is proposed to solve the network clustering problem. Population are divided into different membrane structures on average. The evolutionary algorithm is carried out in the membrane structures. The population are eliminated by the vector of membranes. In the proposed method, two evaluation objectives termed as Kernel J-means and Ratio Cut are to be minimized. Extensive experimental studies comparison with state-of-the-art algorithms proves that the proposed algorithm is effective and promising. PMID- 27670157 TI - Coupling of radiofrequency with magnetic nanoparticles treatment as an alternative physical antibacterial strategy against multiple drug resistant bacteria. AB - Antibiotic resistant bacteria not only affect human health and but also threatens the safety in hospitals and among communities. However, the emergence of drug resistant bacteria is inevitable due to evolutionary selection as a consequence of indiscriminate antibiotic usage. Therefore, it is necessary to develop a novel strategy by which pathogenic bacteria can be eliminated without triggering resistance. We propose a novel magnetic nanoparticle-based physical treatment against pathogenic bacteria, which blocks biofilm formation and kills bacteria. In this approach, multiple drug resistant Staphylococcus aureus USA300 and uropathogenic Escherichia coli CFT073 are trapped to the positively charged magnetic core-shell nanoparticles (MCSNPs) by electrostatic interaction. All the trapped bacteria can be completely killed within 30 min owing to the loss of membrane potential and dysfunction of membrane-associated complexes when exposed to the radiofrequency current. These results indicate that MCSNP-based physical treatment can be an alternative antibacterial strategy without leading to antibiotic resistance, and can be used for many purposes including environmental and therapeutic applications. PMID- 27670159 TI - ? AB - If you asked the country's 600,000 nurses to vote for a pay increase it would probably be significantly higher than the 4.7 per cent MPs awarded themselves last week. But then nurses, unlike politicians don't have the power to vote themselves a pay increase annually. But they have in the past been able to propose a pay rise - the crucial difference being that they rarely got what they asked for. PMID- 27670158 TI - CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes. AB - Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcgamma receptors (FcgammaRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcgammaRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated beta2 integrins and induced TNFalpha secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFalpha-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNgamma, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases. PMID- 27670160 TI - Doctors back nurses in rejecting PRP. AB - Doctors have joined forces with nurses in rejecting performance related pay. PMID- 27670161 TI - Nurses urged to stay firm on pay as MPs get 4.7% increase. AB - The announcement of a 4.7 per cent pay rise for MPs will be used by staff side in the battle for an improved pay award, the Royal College of Nursing said last week. PMID- 27670162 TI - UKCC reveals new figures on nursing. AB - The profile of the average nurse is changing, statistics produced by the UK Central Council reveal. PMID- 27670163 TI - A&E under fire in King's Fund report. AB - Casualty departments in London's hospitals must be given 'enhanced roles', a scathing report by King's Fund Institute has said. The report, released this week, says emergency resources have been stripped to the point where they can no longer cope with unpredictable demand. PMID- 27670164 TI - Hancock: Highest paid but best value leader. AB - RCN General Secretary Christine Hancock is the highest paid union leader in the country, according to a survey by the Certification Office for Trade Unions and Employers Associations . PMID- 27670165 TI - Task group recommended to mediate in Ralph saga. AB - UK Central Council Registrar Colin Ralph, L84,000 a year chief executive of nursing's regulatory body, should go on a three month management course, the committee investigating an official grievance brought against him has recommended. PMID- 27670166 TI - Bottomley's 'openness' code disappoints College. AB - The RCN has expressed 'disappointment' at the draft axle of practice on openness in the NHS launched by health secretary, Virginia Bottomley. PMID- 27670167 TI - New director for SAHC. AB - Nurse Patricia Dawson has been appointed director of the Scottish Asociation of Health Councils. PMID- 27670169 TI - Skill mix exercise a success for health visitors. AB - Health visitors should be freed up to take on the most difficult cases in their areas by the . employment of B and F. grade nurses to handle routine work. Ann Stanton, a health visitor with Edinburgh's Lothian Health Care Trust, said she had initally approached a skill mix exercise with scepticism. PMID- 27670168 TI - Patient's religious and emotional needs important. AB - Nurses must have the knowledge to ask what a patient's religious and emotional needs are if they are to provide total and sensitive care, Rabbi Julia Neuberger told the conference in a keynote speech. PMID- 27670170 TI - New challenge on schizophrenia. AB - The International Council of Nurses has been challenged to bring together nursing research into schizophrenia from around the world and give mental health nurses a body of knowledge from which they could work. The call came last week at an international nursing conference held at the University of Ulster in Coleraine. Nurses heard the plea from Rutgers University Emeritus Professor Hilde- gard Peplau, who decried the failure of nurses to keep pace as other branches of the health professions study the disease. PMID- 27670171 TI - Emergency teams 'a waste of time'. AB - Sending emergency medical teams to strife tom regions is a 'waste of time', the head of nursing for the International Red Cross told the conference. Instead, medical teams should be replaced by engineers and sanitation experts who could provide conditions in which the diseases medical teams were brought in to fight would not survive. PMID- 27670172 TI - Nursing students should study abroad. AB - Nursing students should undertake overseas assignments as a part of their pre registration education, the conference heard. PMID- 27670173 TI - ? AB - Bike aid; a team of crack motorcycle paramedics has taken to the roads. The four person team, a specialist unit of the West Midlands Ambulance Service, will get rapid help to victims of road accidents. PMID- 27670174 TI - 'Genuine' nurses provide better care. AB - Nurses who show 'genuine interest' in the welfare of their patients and obviously enjoy their work provide better quality patient care, a study of quality assessment instruments for nursing has found. PMID- 27670175 TI - Labour Party urged to drop council purchasing plan. AB - The Labour Party has been urged to drop the idea of giving health purchasing power to local authorities. PMID- 27670176 TI - Lothian health signs contract for nurse-led minor injuries service. AB - A nurse-led minor injuries service is to open at Lothian's Western General Hospital in November. PMID- 27670177 TI - New leaflet for agency nurses. AB - The Health and Safety Executive has revised its occupational health guidance for agency nurses in a new leaflet. PMID- 27670178 TI - Tolerance of contraceptive implants improved by good counselling for women. AB - More women will continue using implant contraceptives if they receive careful counselling beforehand, despite disruptions to the menstrual cycle, according to a report published in The Pharmaceutical Journal. PMID- 27670179 TI - Eczema report highlights difficulties for children's health. AB - Atopic eczema has a more detrimental effect on the overall quality of children's health than almost every other skin condition, a recently published report has claimed. PMID- 27670180 TI - Early bypass surgery reduces mortality. AB - Patients suffering heart disease are likely to live longer if they undergo coronary bypass surgery immediately than if they are medically managed and treated with delayed surgery later, a report in The Lancet has claimed. PMID- 27670182 TI - Sudden, severe headache as warning of SAH. AB - Aneurysmal subarachnoid haemorrhage (SAM) is not preceded by sudden headaches or 'warning leaks', researchers from the Netherlands report. PMID- 27670183 TI - Individual regimens in alcohol withdrawal. AB - Individualising the drug regimen used for treating symptoms of alcohol withdrawal has benefits over a fixed schedule, American researchers believe. PMID- 27670184 TI - Does a protein spread Creutzfeldt-Jakob? AB - A 'rogue protein' might be responsible for the transmission of spongiform encephalopathies - diseases such as Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalitis (BSE). PMID- 27670185 TI - Alternative to nappies for urine collection. AB - One brand of sanitary towel is a suitable alternative to disposable nappies for collecting urine specimens for laboratory testing. PMID- 27670187 TI - Nail biting finish for NVQ academics. AB - The article in Nursing Standard entitled 'NVQ for the dole' (Viewpoint, August 24) is yet another example of ostrich-like behaviour by nursing academics. PMID- 27670186 TI - Surveillance camera not candid enough. AB - I am writing to comment on Vic Tadd's article, 'Here's looking at you, kid' (Viewpoint, August 17). PMID- 27670188 TI - The trust conducts itself well... AB - We wish to voice our opinions over the matter of the dismissal of Sister Pat Cooksley (Hospital faces probe over disciplinary delay, News, August 24). PMID- 27670190 TI - Please listen to the voice of experience. AB - I do not really want to reopen the debate about standards within nursing homes. But a lot of nurses and care assistants frequently visit and work in these places, and if standards are not right, staff do speak out, either to the agencies that send us or to health authority inspectors. To my anguish, however, nothing really gets done. PMID- 27670189 TI - Peppercorn rent not to be sneezed at. AB - Unlike Dr Knape, I cannot view L250 a year as 'peppercorn', whatever the sum is used for (Pink, Hands, red faces: UKCC bites back, Letters, August 28). However, the rent was not the issue here, was it, Dr Knape? PMID- 27670191 TI - ...but maybe not that well. AB - I was delighted to read in the news item 'Hospital faces probe over disciplinary delay' (August 24) that the UKCC is likely to question the hospital in the Sister Cooksley affair about the delay of four months in reporting the matter. PMID- 27670192 TI - Common confusion with conduct and law. AB - I feel I must write to comment on what appears to be a fairly common confusion among nurses regarding the UKCC Code of Professional Conduct and the law. PMID- 27670193 TI - ? AB - We welcome all readers' letters but reserve the right to edit them, and withhold names and addresses or both. Please write to Nursing Standard. Viking House 17-19 Peterborough Road, Harrow. Middlesex. HA I 2AX. PMID- 27670194 TI - Information exchange. AB - ?I am currently working with a child named Phillip who is 13 years old and has schleroderma encoup de sabre, a very rare and progressive condition. In order to help him and his family, I am trying to locate anyone who would be willing for Phillip to contact them to share experiences and provide support. And could any professionals working with people with schleroderma encoup de sabre contact me on 0604 236095. Paul McKay Principal Social Worker Disability Services Team Northamptonshire County Council Social Services Team 27 Guildhall Road PU Box 290 Northampton NN1 IBE. PMID- 27670195 TI - Gossip. AB - * It's easy to mock, I know, and we all have our own little peculiarities, but there's a new magazine out aimed specifically at collectors of phone cards. Yes, Publishing reports that Telecard Collector International is about to hit the streets, complete with the obligatory glamorous woman on the front to boost sales. In this case, the woman is Julia Swalha - Saffi, in Absolutely Fabulous - who is obviously a phonecard fan. (Whatever would Patsy say?) But titter ye not. 'Overall, this is an infuriatingly compulsive read,' says Publishing. And with some cards apparently reaching asking prices of L950, the anorak brigade obviously knows a thing or two. But before you start hanging on to all those cards you feed into the nursing home phone, be warned. They apparently increase in value if they are unused. Fabulous. PMID- 27670196 TI - All the fun of the fayre. AB - Hello there, Health Gire Workers! Isn't it exciting to be in a research-based profession? You will remember that research is being carried out in my Unit at the moment to evaluate the effects of health promotion after major surgery. The study is now in full swing, and there have been some interesting results already. PMID- 27670197 TI - Couldn't care less. AB - Muriel is my mother. She is 86, and has not been in hospital since 1949. She has raised four children and is very proud of her 13 grandchildren and eight great grandchildren. She lives in sheltered accommodation near her younger son after retiring from her job as a cook and housekeeper in 1992. PMID- 27670198 TI - Phew, what a scorcher! AB - Viewpoint presents a special picture spread, looking back at events that made the news over the long, hot summer. PMID- 27670200 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27670199 TI - Nursing ethics I: Setting the scene. AB - The subject of ethics is increasingly important in all spheres of life. The changing climate in health care delivery has, however, made it more pressing than ever in the health care field. PMID- 27670201 TI - Loss of RNA expression and allele-specific expression associated with congenital heart disease. AB - Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression-this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression. PMID- 27670202 TI - Significant association between osteoporosis and hearing loss: a systematic review and meta-analysis. AB - INTRODUCTION: There is inconclusive evidence whether osteoporosis increases risk of hearing loss in current literature. OBJECTIVE: We conducted this meta-analysis to determine whether there is an association between hearing loss and osteoporosis. METHODS: This systematic review and meta-analysis was conducted from studies of MEDLINE, EMBASE, and LILACS. Osteoporosis was defined as having a bone mineral density with a T-score of less than -2.5 standard deviation. The outcome was hearing loss as assessed by audiometry or self-reported assessment. Random-effects model and pooled hazard ratio, risk ratio, or odds ratio of hearing loss with 95% confidence intervals were compared between normal bone mineral density and low bone mineral density or osteoporosis. RESULTS: A total of 16 articles underwent full-length review. Overall, there was a statistically significant increased odds of hearing loss in the low bone mineral density or osteoporosis group with odds ratio of 1.20 (95% confidence intervals 1.01-1.42, p=0.04, I2=82%, Pheterogeneity=0.01). However, the study from Helzner et al. reported significantly increase odds of hearing loss in the low bone mineral density in particular area and population included femoral neck of black men 1.37 (95% confidence intervals 1.07-1.76, p=0.01) and total hip of black men 1.36 (95% confidence intervals 1.05-1.76, p=0.02). CONCLUSION: Our study proposed the first meta-analysis that demonstrated a probable association between hearing loss and bone mineral density. Osteoporosis could be a risk factor in hearing loss and might play an important role in age-related hearing loss. PMID- 27670204 TI - 210Po bioaccumulation and trophic transfer in marine food chains in the northern Arabian Gulf. AB - The tendency of 210Po to concentrate in body tissue poses a serious concern of radiological safety. This study compiles available information and presents recent 210Po data for the marine food web in the northern Gulf waters. Since 210Po is concentrated in marine biota, a large number of samples of various marine organisms covering several trophic levels, from microalgae to sharks, were analyzed. 210Po was found to be highly concentrated in several marine species with the highest 210Po concentrations found in yellowfin tuna, i.e. 37.3-44.9, 451-548, and 1511-1693 Bq kg-1 wwt in muscle, digestive system and liver, respectively. In most dissected fish samples, 210Po showed increasing concentrations in the following order: edible tissue, gills, digestive system, liver and fecal matter. Fish feces had 210Po concentrations several orders of magnitude higher than that in seawater, fish muscle, and the fishes' ingested food. The high 210Po concentration in fish fecal matter suggests that the bulk of 210Po content in fish is eventually excreted back into the environment as fecal pellets. In most fish high concentrations were noted in liver, with the highest 210Po concentration recorded in yellowfin tuna liver. Moreover, 210Po concentration in the soft tissue of tunicate and bryozoan samples were 872-1012 and 402-527 Bq kg-1 wwt, respectively, far higher than that in fish muscle (0.04 44.9 Bq kg-1 wwt). It was observed that the maximum 210Po concentration in edible fish tissue among the fish in trophic level 2 was an order of magnitude lower than those in trophic level 3 and two orders of magnitude lower compared to fish in trophic level 4. The highest concentrations in the muscle tissue were observed in the following order: tunicate > bryozoan > mollusc > crustacean > algae > fish. Among all the biota analyzed, the highest overall concentration of 210Po was noted in yellowfin tuna (Thunnus albacores) indicating a potential biomagnification of 210Po in this particular top predator species. In general, 210Po concentrations found in the commercially important fish from Kuwaiti waters were comparable to levels that have been reported for similar fish species from several other marine areas worldwide. PMID- 27670203 TI - Association between desloratadine and prednisolone in the treatment of children with acute symptoms of allergic rhinitis: a double-blind, randomized and controlled clinical trial. AB - INTRODUCTION: A combination of antihistamines and oral corticosteroids is often used to treat acute symptoms of allergic rhinitis. OBJECTIVE: To evaluate safety and efficacy of desloratadine plus prednisolone in the treatment of acute symptoms of children (2-12 years) with allergic rhinitis, and to compare it to dexchlorpheniramine plus betamethasone. METHODS: Children with moderate/severe persistent allergic rhinitis and symptomatic (nasal symptoms score [0-12]>=6) were allocated in a double-blind, randomized fashion to receive dexchlorpheniramine plus betamethasone (n=105; three daily doses) or desloratadine plus prednisolone (n=105; single dose followed by two of placebo) for 7 days. At the beginning and end of the evaluation, the following were obtained: nasal symptoms score, extra nasal symptoms score, peak nasal inspiratory flow, blood biochemistry, and electrocardiogram. Ninety-six children of the dexchlorpheniramine plus betamethasone group and 98 of the desloratadine plus prednisolone group completed the protocol. RESULTS: The two groups were similar regarding initial and final nasal symptoms scores, extra nasal symptoms scores and peak nasal inspiratory flow. A drop of 76.4% and 79.1% for nasal symptoms score, 86.0% and 79.2% for extra nasal symptoms score, as well as an increase of 25.2% and 24.3% for peak nasal inspiratory flow occurred for those treated with desloratadine plus prednisolone and dexchlorpheniramine plus betamethasone, respectively. There were no significant changes in blood chemistry. Sinus tachycardia was the most frequent electrocardiogram change, but with no clinical significance. Drowsiness was reported significantly more often among those of dexchlorpheniramine plus betamethasone group (17.14%*8.57%, respectively). CONCLUSION: The desloratadine plus prednisolone combination was able to effectively control acute symptoms of rhinitis in children, improving symptoms and nasal function. Compared to the dexchlorpheniramine plus betamethasone combination, it showed similar clinical action, but with a lower incidence of adverse events and higher dosing convenience. PMID- 27670205 TI - Modelling the relationship between zooplankton biomass and environmental variations in the distribution of 210Po during a one year cycle in northwestern Mediterranean coastal waters. AB - To clarify the relationship between zooplankton biomass and the environmental kinetics of the natural radionuclide 210Po during a one-year period (October 1995 to November 1996) in northwestern Mediterranean coastal waters, a modelling analysis was applied. Using 210Po concentrations in seawater and zooplankton, the 210Po uptake rate constant from food for zooplankton was evaluated using a biokinetics calculation involving the uptake and the excretion rate constants between seawater and zooplankton. Using the transfer constants obtained, the 210Po concentrations in zooplankton were reconstructed and validated by observed concentrations. The simulation results were in good agreement with the measured 210Po concentrations in zooplankton. Assuming that 210Po fecal excretion represents the majority of the excretion of 210Po from zooplankton, the fecal matter associated 210Po vertical flux was calculated, and compared with the observed vertical fluxes of 210Po measured in sediment traps. The modelling evaluation showed that fecal pellet vertical transport could not fully explain the observed sinking fluxes of particulate organic matter at 150 m depth, suggesting that other sinking biodetrital aggregates are also important components of the plankton-derived vertical flux of 210Po. The relationship between 210Po concentration in seawater and that in rain and dry fallout and their potential effect on 210Po concentrations in zooplankton at this location were also examined. A similar, but diphased trend between 210Po in zooplankton and 210Po in rain and dry fallout deposition rate was demonstrated. 210Po concentrations in the dissolved phase of seawater tended to diminish as mean daily rainfall increased suggesting that rain inputs serve as a 210Po dilution mechanism in seawater at this location. PMID- 27670206 TI - Malformations of Cortical Development: From Postnatal to Fetal Imaging. AB - Abnormal fetal corticogenesis results in malformations of cortical development (MCD). Abnormal cell proliferation leads to microcephaly or megalencephaly, incomplete neuronal migration results in heterotopia and lissencephaly, neuronal overmigration manifests as cobblestone malformations, and anomalous postmigrational cortical organization is responsible for polymicrogyria and focal cortical dysplasias. MCD comprises various congenital brain disorders, caused by different genetic, infectious, or vascular etiologies and is associated with significant neurological morbidity. Although MCD are rarely diagnosed prenatally, both dedicated multiplanar neurosonography and magnetic resonance imaging enable good demonstration of fetal cortical development. The imaging signs of fetal MCD are: delayed or absent cerebral sulcation; premature abnormal sulci; thin and irregular hemispheric parenchyma; wide abnormal overdeveloped gyri; wide opening of isolated sulci; nodular bulging into the lateral ventricles; cortical clefts; intraparenchymal echogenic nodules; and cortical thickening. The postnatal and prenatal imaging features of four main malformations of cortical development lissencephaly, cobblestone malformations, periventricular nodular heterotopia, and polymicrogyria-are described. PMID- 27670207 TI - Medical Management of Parkinson's Disease after Initiation of Deep Brain Stimulation. AB - In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate). As for the psychiatric problems so frequently reported in PD patients, researchers have directed their attention to the complex interplay between stimulation and reduction of dopaminergic drugs only recently. In conclusion, studies addressing medical management following DBS are still needed and will certainly contribute to the ultimate success of DBS procedures. PMID- 27670208 TI - Fast-Track Systems Improve Timely Carotid Endarterectomy in Stroke Prevention Outpatients. AB - BACKGROUND: For optimal stroke prevention, best practices guidelines recommend carotid endarterectomy (CEA) for symptomatic patients within two weeks; however, 2013 Ontario data indicated that only 9% of eligible patients from outpatient Stroke Prevention Clinics (SPCs) achieved this target. The goal of our study was to identify modifiable system factors that could enhance the quality and timeliness of care among patients needing urgent CEA. METHODS: We conducted a retrospective chart review of transient ischemic attack/stroke patients assessed in Champlain Local Health Integrated Network SPCs between 2011 and 2014 who subsequently underwent CEA. Descriptive statistics were used to define patient characteristics, timelines from symptom onset to CEA, and system factors that contributed to delays or improvements in care. Multivariate analysis was used to determine statistically significant variations between groups. RESULTS: Seventy five records were eligible for study inclusion. Median time from initial symptoms to CEA was 31 days, with 21.3% of patients undergoing surgery within 2 weeks. Significant delays were common in patient presentation and assessment following symptom onset, wait times for vascular imaging and neurological assessment, and time from surgical assessment to CEA completion. Rapid testing and triage, coupled with collaborative initiatives among SPC, surgical, and radiology teams were associated with significantly improved timelines. CONCLUSIONS: Success factors for rapid CEA are multifaceted, including system changes that address public awareness of stroke and 911 response, improvements in vascular imaging access, and redesign of clinical services to promote collaboration and fast tracking of care. Implementation of performance measures to monitor and guide clinical innovations is recommended. PMID- 27670209 TI - Validation of Montreal Cognitive Assessment, MoCA, Alternate French Versions. AB - Objective background: The Montreal Cognitive Assessment (MoCA) is a questionnaire that has been developed to help physicians around the world diagnose a patient's cognitive ability. Available in multiple languages and for use in multiple countries worldwide, the goal of this study was to validate the alternate versions 2 and 3 of the French MoCA test to assist physicians in the detection of mild cognitive impairment (MCI), while decreasing the learning effect upon frequent testing. METHODS: A validation study was conducted at the MoCA Clinic and Institute in Quebec, Canada. The subject population consisted of 25 patients diagnosed with MCI meeting Petersen criteria and 25 healthy subjects serving as the normal control (NC) group. Three MoCA test versions were administered in the French language in random order within one session. Scores obtained in all three versions in MCI and NC groups were assessed for reliability and consistency from one version to the next. RESULTS: On average, scores obtained in each subject group (MCI and NC) fell within their corresponding diagnostic ranges (score above 26 points for NC patients versus scores below 26 points for MCI patients). Difference in scores observed between the original French MoCA version and the two alternate versions in each subject cohort were minimal and not considered clinically significant. CONCLUSIONS: All three test versions of the French MoCA are considered equivalent in diagnostic reliability and consistency and contribute to decreasing the potential learning effect when patients are required to repeat the test frequently. PMID- 27670210 TI - Knowledge and Attitudes About Epilepsy Surgery Among Family Doctors in Ontario. AB - BACKGROUND: Approximately 30% of patients with epilepsy have medically intractable seizures, and a proportion of them are candidates for surgical treatment. The efficacy and safety of epilepsy surgery have been supported by a large number of studies, yet only a small minority of such patients in Ontario receive surgery. METHODS: Family physicians in Ontario were surveyed regarding demographics, referral practices and general knowledge about epilepsy surgery. Four hundred surveys were mailed to randomly selected family physicians using contact information from the College of Physicians and Surgeons of Ontario website. RESULTS: The response rate was 50%. The majority of family physicians (81%) always refer patients with epilepsy, most often to neurologists. General knowledge of epilepsy was mixed, with 53.7% feeling that surgery should be considered in selected cases for the treatment of epilepsy, though 53.2% did not know what type of epilepsy could be surgically treated. CONCLUSIONS: The results suggest a relatively low level of knowledge among family physicians in terms of when surgery ought to be considered, the types of epilepsy that are amenable to surgical treatment and the risks and benefits of epilepsy surgery. A lack of knowledge in these areas may partly underlie the low referral rates of epilepsy patients, though the results show that the majority of family physicians refer their patients with epilepsy to neurologists. Other factors must be considered, such as access to neurologists, epileptologists and surgical resources. Education campaigns directed at family physicians may improve knowledge and change referral practices. Future studies need to examine these possibilities. PMID- 27670211 TI - Myotonic Dystrophy and Huntington's Disease Care: "We Like to Think We're Making a Difference". AB - BACKGROUND: Patient-centered care for individuals with myotonic dystrophy (DM1) and Huntington's disease (HD)-chronic, progressive, and life-limiting neurological conditions-may be challenged by patients' cognitive and behavioral impairments. However, no research has explored health care providers' (HCPs') perspectives about patient-centered care provision for these patients along their disease trajectory. METHODS: Constructivist grounded theory informed the iterative data collection and analysis process. Eleven DM1 or HD HCPs participated in semistructured interviews, and three stages of coding were used to analyze their interview transcripts. Codes were collapsed into themes and categories. RESULTS: Three categories including an evolving care approach, fluid roles, and making a difference were identified. Participants described that their clinical care approach evolved depending on the patient's disease stage and caregivers' degree of involvement. HCPs described that their main goal was to provide hope to patients and caregivers through medical management, crisis prevention, support, and advocacy. Despite the lack of curative treatments, HCPs perceived that patients benefited from ongoing clinical care provided by proactive clinicians. CONCLUSIONS: Providing care for individuals with DM1 and HD is a balancing act. HCPs must strike a balance between (1) the frustrations and rewards of patient-centered care provision, (2) addressing symptoms and preventing and managing crises while focusing on patients' and caregivers' quality of life concerns, and (3) advocating for patients while addressing caregivers' needs. This raises important questions: Is patient-centered care possible for patients with cognitive decline? Does chronic neurological care need to evolve to better address patients' and caregivers' complex needs? PMID- 27670212 TI - Oxidative Stress and Environmental Exposures are Associated with Multiple System Atrophy in Chinese Patients. AB - OBJECTIVE: Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA). The aim of this study is to examine oxidant biomarkers including homocysteine (Hcys), bilirubin, uric acid, lipids, and potential environmental risk factors and to ascertain whether these data correlate with MSA in a Chinese population. METHODS: In this study, serum levels of Hcys, bilirubin, uric acid, and lipids were studied in 55 MSA patients and 76 healthy controls (HCs). Education, anti-parkinsonian agent usage, smoking, drinking, farming, and living area of the subjects also were analyzed. The Unified MSA Rating Scale (UMSARS), Hoehn & Yahr stage, International Cooperative Ataxia Rating Scale, and Mini Mental State Examination were used to assess the disease severity, the parkinsonism, ataxia, and the cognitive ability of MSA, respectively. RESULTS: The levels of Hcys were higher (p<0.001) and those of total bilirubin (p=0.007), indirect bilirubin (p=0.011), and total cholesterol (p=0.046) were lower in MSA patients than in healthy controls, whereas uric acid levels did not differ significantly between MSA and healthy controls. Moreover, Hcys levels in MSA patients had positive correlations with illness duration (r s =0.422, p=0.001) and UMSARS-I (r s =0.555, p<0.001), respectively. High-density lipoprotein cholesterol levels were negatively correlated with UMSARS-I (r s =-0.325, p=0.015). Farming was more frequent in MSA patients (1-20 years: odds ratio, 6.36; p20 years: odds ratio, 10.26; p=0.001), whereas current smoking was less frequent (odds ratio, 0.13, p=0.002). CONCLUSIONS: Elevated Hcys and decreased high-density lipoprotein cholesterol may be associated with the disease severity of MSA. Environmental exposures such as farming and smoking may contribute to the occurrence but not the progression of MSA. PMID- 27670213 TI - Nonalcoholic Wernicke Encephalopathy: An Entity Not to Be Missed! PMID- 27670214 TI - Vessel Wall Contrast Enhancement on Magnetic Resonance Imaging May Be Suggestive for Future Development of Further Arterial Changes. PMID- 27670215 TI - Temporal Lobe Atrophy May Be Underrecognized in Older Patients with New-Onset Epilepsy. PMID- 27670216 TI - Oculomotor Palsy in Spontaneous Intracranial Hypotension: Case Report and Review of the Literature. PMID- 27670218 TI - Yb3+/Ho3+ Co-Doped Apatite Upconversion Nanoparticles to Distinguish Implanted Material from Bone Tissue. AB - The exploration of bone reconstruction with time requires the combination of a biological method and a chemical technique. Lanthanide Yb3+ and Ho3+ co-doped fluorapatite (FA:Yb3+/Ho3+) and hydroxyapatite (HA:Yb3+/Ho3+) particles with varying dopant concentrations were prepared by hydrothermal synthesis and thermal activation. Controllable green and red upconversion emissions were generated under 980 nm near-infrared excitation; the FA:Yb3+/Ho3+ particles resulted in superior green luminescence, while HA:Yb3+/Ho3+ dominated in red emission. The difference in the green and red emission behavior was dependent on the lattice structure and composition. Two possible lattice models were proposed for Yb3+/Ho3+ co-doped HA and FA along the hydroxyl channel and fluorine channel of the apatite crystal structure. We first reported the use of the upconversion apatite particles to clearly distinguish implanted material from bone tissue on stained histological sections of harvested in vivo samples. The superposition of the tissue image and material image is a creative method to show the material tissue distribution and interrelation. The upconversion apatite particles and image superposition method provide a novel strategy for long-term discriminable fluorescence tracking of implanted material or scaffold during bone regeneration. PMID- 27670217 TI - Aberrant Meiotic Prophase I Leads to Genic Male Sterility in the Novel TE5A Mutant of Brassica napus. AB - Genic male sterility (GMS) has already been extensively utilized for hybrid rapeseed production. TE5A is a novel thermo-sensitive dominant GMS line in Brassica napus, however, its mechanisms of GMS remain largely unclear. Histological and Transmission electron microscopy (TEM) analyses of anthers showed that the male gamete development of TE5A was arrested at meiosis prophase I. EdU uptake of S-phase meiocytes revealed that the TE5A mutant could accomplish DNA replication, however, chromosomal and fluorescence in situ hybridization (FISH) analyses of TE5A showed that homologous chromosomes could not pair, synapse, condense and form bivalents. We then analyzed the transcriptome differences between young floral buds of sterile plants and its near-isogenic fertile plants through RNA-Seq. A total of 3,841 differentially expressed genes (DEGs) were obtained, some of which were associated with homologous chromosome behavior and cell cycle control during meiosis. Dynamic expression changes of selected candidate DEGs were then analyzed at different anther developmental stages. The present study not only demonstrated that the TE5A mutant had defects in meiotic prophase I via detailed cytological analysis, but also provided a global insight into GMS-associated DEGs and elucidated the mechanisms of GMS in TE5A through RNA-Seq. PMID- 27670219 TI - Advancing environmental health surveillance in the US through a national human biomonitoring network. AB - The United States lacks a comprehensive, nationally-coordinated, state-based environmental health surveillance system. This lack of infrastructure leads to: * varying levels of understanding of chemical exposures at the state & local levels * often inefficient public health responses to chemical exposure emergencies (such as those that occurred in the Flint drinking water crisis, the Gold King mine spill, the Elk river spill and the Gulf Coast oil spill) * reduced ability to measure the impact of public health interventions or environmental policies * less efficient use of resources for cleaning up environmental contamination Establishing the National Biomonitoring Network serves as a step toward building a national, state-based environmental health surveillance system. The Network builds upon CDC investments in emergency preparedness and environmental public health tracking, which have created advanced chemical analysis and information sharing capabilities in the state public health systems. The short-term goal of the network is to harmonize approaches to human biomonitoring in the US, thus increasing the comparability of human biomonitoring data across states and communities. The long-term goal is to compile baseline data on exposures at the state level, similar to data found in CDC's National Report on Human Exposure to Environmental Chemicals. Barriers to success for this network include: available resources, effective risk communication strategies, data comparability & sharing, and political will. Anticipated benefits include high quality data on which to base public health and environmental decisions, data with which to assess the success of public health interventions, improved risk assessments for chemicals, and new ways to prioritize environmental health research. PMID- 27670221 TI - Advances in the pathophysiology of primary immune thrombocytopenia. AB - OBJECTIVES: Classically, immune thrombocytopenia (ITP) was thought to be caused by the destruction and insufficient production of platelets, as mediated by autoantibodies. More recently other immune mechanisms that contribute to the disease have been discovered. This review attempts to address the main unresolved questions in ITP. METHODS: We review the most current knowledge of the pathophysiology of ITP. Immunological effects of available therapies are also described. DISCUSSION: The trigger may be a loss of tolerance due to molecular mimicry with cross-reaction of antibodies arising from infectious agents or drugs, genetic factors, and/or platelet Toll receptors. This loss of tolerance activates autoreactive effector B and T lymphocytes, which in turn initiates platelet destruction, mediated by cytotoxic T lymphocytes and the release of pro inflammatory cytokines (IL-2/IL-17) by T helper (Th) cells (Th1/Th17). Th2 (anti inflammatory) and regulatory B (Breg) and Treg cells are also inhibited (with decrease in IL-10/TGF-beta), which leads to the disease becoming chronic. Some isotypes of autoantibodies may increase the bleeding risk. Corticosteroids, rituximab, and thrombopoietin receptor agonists (A-TPOs) all increase levels of Tregs and TGF-beta. The A-TPOs also increase Breg levels, which could explain why complete remission has been seen in some cases. CONCLUSION: A better understanding of the immunomodulatory effects of each ITP therapy is needed to best manage the disease. PMID- 27670220 TI - RIFM fragrance ingredient safety assessment, linalyl benzoate, CAS Registry Number 126-64-7. AB - The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data show that this material is not genotoxic. Data from the suitable read across analog linalyl phenylacetate (CAS # 7143-69-3) show that this material does not have skin sensitization potential. The repeated dose toxicity endpoint was completed using linalyl cinnamate (CAS # 78-37-5) as a suitable read across analog, which provided a MOE > 100. The developmental and reproductive toxicity endpoint was completed using linalool (CAS # 78-70-6), dehydrolinalool (CAS # 29171-20-8), benzoic acid (CAS # 65-85-0) and sodium benzoate (CAS # 532 32-1) as suitable read across analogs, which provided a MOE > 100. The local respiratory toxicity endpoint was completed using linalool (CAS # 78-70-6) and benzoic acid (CAS # 65-85-0) as suitable read across analogs, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework along with data from the suitable read across analog linalyl cinnamate (CAS # 78-375). PMID- 27670222 TI - Evaluation of a Serious Self-Regulation Game Intervention for Overweight-Related Behaviors ("Balance It"): A Pilot Study. AB - BACKGROUND: Serious games have the potential to promote health behavior. Because overweight is still a major issue among secondary vocational education students in the Netherlands, this study piloted the effects of "Balance It," a serious self-regulation game intervention targeting students' overweight-related behaviors: dietary intake and physical activity (PA). OBJECTIVE: We aimed to pilot the effects of Balance It on secondary vocational education students' dietary intake and PA. METHODS: In total, 501 secondary vocational education students participated at baseline (intervention: n=250; control: n=251) in this pre-post cluster randomized trial. After 4 weeks, at immediate posttest, 231 students filled in the posttest questionnaire (intervention: n=105; control: n=126). The sample had a mean age of 17.28 (SD 1.26, range 15-21) years, 62.8% (145/231) were female, and 26.8% (62/231) had a non-Dutch background. Body mass index (BMI kg/m2) ranged from 14.4 to 31.1 (mean 21.1, SD 3.3). The intervention and control groups were compared on the primary (behavioral) outcomes of dietary intake (fruit and vegetable consumption, snack consumption, and soft drink consumption) and PA (moderate and vigorous). Additionally, we explored (1) differences between the intervention and control groups in determinants of dietary intake and PA, including attitude, self-efficacy, intention, barrier identification, action planning, and action control, and (2) differences between active (intervention) users and the control group in dietary intake, PA, and associated determinants. RESULTS: After corrections for multiple testing, we did not find significant differences between the intervention group and control group in terms of dietary intake, PA, and determinants of dietary intake and PA. Exploratory research indicated that only 27.6% (29/105) of the intervention group reported actual intervention use (ie, active users). For exploratory reasons, we compared the active users (n=29) with the control group (n=124) and corrected for multiple testing. Results showed that active users' snack consumption decreased more strongly (active users: mean change=-0.20; control group: mean change=-0.08; beta=-0.36, P=.01, R2 change=.05), and their use of active transport had a stronger increase (active users: mean change=0.92; control group=-0.12; beta=1.58, P=.02, R2 change=.03) than the control group. Results also revealed significant differences in action planning (active users: mean change=0.42; control group: mean change=0.07; beta=0.91, P=.01, R2 change=.04) and action control (active users: mean change=0.63; control group: mean change=-0.05; beta=1.25, P=.001, R2 change=.08) in terms of unhealthy eating. CONCLUSIONS: The Balance It intervention did not show favorable effects on dietary intake and PA compared to the control condition. However, only a small number of people in the intervention condition actually used Balance It (27.6%). Exploratory analyses did suggest that, if used as planned, Balance It could contribute to changing dietary intake and PA behaviors, albeit it remains debatable whether this would be sufficient to prevent overweight. PMID- 27670223 TI - Extracorporeal Membrane Oxygenation for Hemophagocytic Lymphohistiocytosis. AB - BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare hematological disease characterized by an excessive inflammatory response to various triggers, resulting in rapid multi-organ failure. Its incidence may be underestimated due to its rarity, its variable clinical presentation, and its high mortality rate prior to diagnosis. Oftentimes, HLH is mistaken for refractory sepsis and improperly treated as such. Left untreated, the disease is universally fatal. With treatment, case series of adults with HLH report a 30-day mortality of up to 44% and an overall mortality of up to 75%. CASE REPORT We describe the use of extracorporeal membrane oxygenation (ECMO) in a previously healthy young man with HLH and acute respiratory distress syndrome (ARDS), a common sequela of HLH. ECMO was employed to provide temporary hemodynamic support, allowing for recovery of pulmonary function compromised during the initial cytokine storm. Additionally, and perhaps more importantly, implementation of ECMO provided the time necessary for the eventual diagnosis and treatment of HLH. CONCLUSIONS Although limited case reports and case series suggest that the use of ECMO in pediatric patients with HLH is associated with high mortality, our experience suggests that ECMO should not be rejected as a supportive modality in adults with HLH who have potentially recoverable cardiopulmonary function. We believe that ECMO may be appropriately instituted in select patients with HLH, or in rapidly deteriorating patients with an unknown illness refractory to conventional therapy, to allow for end-organ recovery, to reach a diagnosis, and to administer appropriate therapy. PMID- 27670224 TI - Genetic variability and forensic efficiency of 39 microsatellite loci in the Li ethnic group from Hainan Island in the South China Sea. AB - BACKGROUND: Investigation of allele and genotype frequencies of microsatellite loci in various populations is an essential pre-requisite in forensic application. AIM: The present study obtained population genetic data and forensic parameters of 39 autosomal Short Tandem Repeats (STRs) loci from a Chinese Li ethnic group and estimated the genetic relationships between Li and other reference populations. SUBJECTS AND METHODS: Thirty-nine STR loci, which include D19S433, D5S818, D21S11, D18S51, D6S1043, D3S1358, D13S317, D7S820, D16S539, CSF1PO, Penta D, D2S441, vWA, D8S1179, TPOX, Penta E, TH01, D12S391, D2S1338, FGA, D6S477, D18S535, D19S253, D15S659, D11S2368, D20S470, D1S1656, D22 GATA198B05, D8S1132, D4S2366, D21S1270, D13S325, D9S925, D3S3045, D14S608, D10S1435, D7S3048, D17S1290 and D5S2500, were amplified in two multiplex DNA-STR fluorescence detection systems for 189 unrelated healthy individuals of the Chinese Li ethnic group. The allele frequency distribution and several parameters commonly used in forensic science were statistically analysed. RESULTS: A total of 378 alleles were observed with corresponding allelic frequencies ranging from 0.0026-0.5899. The power of discrimination and power of exclusion ranged from 0.7569-0.9672 and 0.2513-0.7355, respectively. The power of exclusion (PE) ranged from 0.2580-0.7943 for trio paternity cases and 0.1693-0.5940 for duo paternity cases. The polymorphism information content (PIC) ranged from 0.5001-0.8611. The cumulative match probability across these 39 loci was 2.4242 * 10-38. CONCLUSION: The results indicate that 39 STR loci are polymorphic among the Li ethnic group in Hainan Island in the South China Sea. This set of polymorphic STR loci provide highly polymorphic information and forensic efficiency for forensic individual identification and paternity testing, as well as basic population data for population genetics and anthropological research. PMID- 27670225 TI - Role of Settling Particles on Mercury Methylation in the Oxic Water Column of Freshwater Systems. AB - As the methylation of inorganic mercury to neurotoxic methylmercury has been attributed to the activity of anaerobic bacteria, the formation of methylmercury in the oxic water column of marine ecosystems has puzzled scientists over the past years. Here we show for the first time that methylmercury can be produced in particles sinking through oxygenated water column of lakes. Total mercury and methylmercury concentrations were measured in the settling particles and in surface sediments of the largest freshwater lake in Western Europe (Lake Geneva). While total mercury concentration differences between sediments and settling particles were not significant, methylmercury concentrations were about ten-fold greater in settling particles. Methylmercury demethylation rate constants (kd) were of similar magnitude in both compartments. In contrast, mercury methylation rate constants (km) were one order of magnitude greater in settling particles. The net potential for methylmercury formation, assessed by the ratio between the two rate constants (km kd-1), was therefore up to ten fold greater in settling particles, denoting that in situ transformations likely contributed to the high methylmercury concentration found in settling particles. Mercury methylation was inhibited (~80%) in settling particles amended with molybdate, demonstrating the prominent role of biological sulfate-reduction in the process. PMID- 27670226 TI - Stereoselective Multicomponent Reactions Using Zincate Nucleophiles: beta Dicarbonyl Synthesis and Functionalization. AB - A general strategy for conjugate addition-C-acylation that enables the synthesis of enantioenriched beta-dicarbonyl compounds is described. A novel method for derivatizing these adducts by stereo- and site-selective zinc-catalyzed addition of alkyllithium reagents is also reported. These reactions can be performed in tandem to achieve an enantio- and diastereoselective four-component coupling. The in situ generation of weakly basic lithium zincate species is central to the success of all three transformations. PMID- 27670228 TI - Skin cancer: Avelumab effective against Merkel-cell carcinoma. PMID- 27670229 TI - Kidney cancer: Papillary features predict survival in ncRCC. PMID- 27670230 TI - Thyroid cancer: BRAF and/or TERT mutations increase mortality. PMID- 27670227 TI - Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis. AB - BACKGROUND AND AIMS: Focal EMR followed by radiofrequency ablation (f-EMR + RFA) and stepwise or complete EMR (s-EMR) are established strategies for eradication of Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC)/intramucosal carcinoma (IMC). The objective of this study was to derive pooled rates of efficacy and safety of individual methods in a large cohort of patients with BE and to indirectly compare the 2 methods. METHODS: PubMed, Embase, Web of Science, Cochrane, and major conference proceedings were searched. A systematic review and pooled analysis were carried out to determine the following outcomes in patients with BE undergoing either f EMR + RFA or s-EMR: (1) complete eradication rates of neoplasia (CE-N) and intestinal metaplasia (CE-IM); (2) recurrence rates of cancer (EAC), dysplasia, and IM; (3) incidence rates of adverse events. Mixed logistic regression was performed as an exploratory analysis to examine differences in outcomes between the 2 methods. RESULTS: Nine studies (774 patients) of f-EMR + RFA and 11 studies (751 patients) of s-EMR were included. Patients undergoing f-EMR + RFA had high BE eradication rates (CE-N, 93.4%; CE-IM, 73.1%), whereas strictures occurred in 10.2%, bleeding in 1.1%, and perforations in 0.2% of patients. Recurrence of EAC, dysplasia, and IM was 1.4%, 2.6%, and 16.1%, respectively, in this group. Patients undergoing s-EMR also showed high BE eradication rates (CE-N, 94.9%; CE IM, 79.6%) but a higher rate of adverse events (strictures in 33.5%, bleeding in 7.5%, and perforation in 1.3%). Recurrence of EAC, dysplasia, and IM was 0.7%, 3.3%, and 12.1%, respectively, in the s-EMR group. Mixed logistic regression showed that patients undergoing s-EMR might be more likely to develop esophageal strictures (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.61-13.85; P = .005), perforation (OR, 7.00; 95% CI, 1.56-31.33; P = .01), and bleeding (OR, 6.88; 95% CI, 2.19-21.62; P = 0.001) compared with f-EMR + RFA. CONCLUSIONS: In patients with HGD/EAC, f-EMR followed by RFA seems to be equally effective as and safer than s-EMR. PMID- 27670232 TI - In the news: From IBCD 2016. PMID- 27670231 TI - Gastrointestinal cancer: Mutational signatures reveal distinct subgroups. PMID- 27670233 TI - Lung cancer: Stage III NSCLC - is it time to centralize care? PMID- 27670234 TI - Age-related changes in sleep EEG are attenuated in highly intelligent individuals. AB - Impaired sleep is a frequent complaint in ageing and a risk factor for many diseases. Non-rapid eye movement (NREM) sleep EEG delta power reflects neural plasticity and, in line with age-related cognitive decline, decreases with age. Individuals with higher general intelligence are less affected by age-related cognitive decline or other disorders and have longer lifespans. We investigated the correlation between age and EEG power in 159 healthy human subjects (age range: 17-69 years), and compared an average (IQ<120; N=87) with a high (IQ>=120; N=72) intelligence subgroup. We found less age-related decrease in all-night relative NREM sleep EEG delta power in the high intelligence subgroup. Our results suggest that highly intelligent individuals are less affected by the sleep-related effects of biological ageing, and therefore potentially less at risk for age-related cognitive deficits and other diseases. PMID- 27670235 TI - Conscious and unconscious performance monitoring: Evidence from patients with schizophrenia. AB - The ability to detect our own errors is an essential component of action monitoring. Using a masking paradigm in normal adults, we recently discovered that some error-detection processes can proceed without awareness, while other markers of performance monitoring such as the Error-Related Negativity (ERN) are tightly linked to conscious perception. Interestingly, research on cognitive deficit in schizophrenia has shown that the ERN is altered in these patients. In the present study, we therefore tested if the error detection impairment in schizophrenia is specific to conscious perception or is also found under non conscious conditions, probing whether these performance monitoring processes are truly distinct. Thirteen patients with schizophrenia and thirteen age-matched healthy control subjects performed a speeded number comparison task on masked stimuli while EEG and MEG signals were recorded. Conscious perception and error detection were assessed on a trial-by-trial basis using subjective reports of visibility and confidence. We found that patients with schizophrenia presented altered cingulate error-detection responses in conscious trials, as reflected by a decreased ERN. By contrast, on unconscious trials, both controls and schizophrenia patients performed above chance in evaluating the likelihood of having made an error. This dissociation confirms the existence of two distinct performance monitoring systems, and suggests that conscious metacognition in schizophrenia is specifically altered while non-conscious performance monitoring remains preserved. PMID- 27670236 TI - Psychotic-like experiences, trauma and related risk factors among "left-behind" children in China. AB - BACKGROUND: Large scale migration of workers due to wage differences across regions of China has separated millions of children, called "left-behind children" from their parents. Psychotic-like experiences (PLEs) are thought to be associated with childhood deprivation and may predict later psychotic disorders but have not been studied in this potentially vulnerable population. METHODS: Data were collected from representative samples of students in thirteen middle schools in the Xiangxi region and Changsha city of Hunan province (N=6623), of whom 1360 (21.3%) were "left-behind" children. Children were surveyed with the positive frequency subscales of the Community Assessment of Psychic Experiences and the Trauma History Questionnaire child version. RESULTS: More "left-behind" children reported experiencing PLEs than others. They also scored higher on the overall frequency of PLEs, severity of childhood trauma, and the subjectively perceived psychological impact of trauma both at the time of the events and at present. Compared with "left-behind" children raised by a parent or by grandparents, those raised by others reported suffering more severe impact both at the time of the events and at present. Among "left-behind" children trauma history was the most important correlate of PLEs followed by Han ethnicity, older age, and not having a stable family income. CONCLUSION: "Left-behind" children are at higher risk for PLEs and suffer more traumatic events than other Chinese children. Interventions that reduce trauma risk and improve relationships with caregivers may be helpful, especially for older "left-behind" children. PMID- 27670237 TI - A meta-analysis of metacognitive beliefs as implicated in the self-regulatory executive function model in clinical psychosis. AB - This meta-analysis investigated whether the five metacognitive beliefs implicated in the Self-Regulatory Executive Function (S-REF) model (Wells and Matthews, 1994; Wells and Matthews, 1996) are elevated in people with clinical psychosis compared to people with emotional disorder and non-psychiatric controls. The review followed guidance set-out in the PRISMA statement. Primary analyses compared summary effect sizes on each sub-scale of the Metacognitions Questionnaire (MCQ) for people with psychosis and non-psychiatric controls; and people with psychosis and people with emotional disorder. Eleven eligible studies were identified comprised of 568 psychosis participants, 212 emotional disorder participants and 776 non-psychiatric controls. Findings indicated that people with psychosis had higher scores on all sub-scales of the MCQ compared to non psychiatric controls; and higher scores on the positive beliefs about worry sub scale compared to people with emotional disorder. This suggests metacognitive beliefs may be associated with the presence of psychological disorder and distress in general, rather than specific diagnoses. Implications for models of psychosis and treatment are discussed. PMID- 27670238 TI - Delusional ideation during the perinatal period in a community sample. AB - BACKGROUND: Despite the prevalence of mental health problems during the perinatal period, little research has examined psychotic symptoms in a community sample across pregnancy and the postpartum. Exposure to environmental risk factors, and immigration in particular, are associated with increased risk for psychotic disorders. The current investigation examined whether psychosocial risk and immigrant status would predict levels of delusional ideation across the perinatal period when controlling for depression, anxiety, and demographic factors. METHODS: A community sample of 316 pregnant women was assessed at 12-14 and 32 34weeks gestation during routine clinic visits, and at 7-9weeks postpartum during a home visit. Measures included self-report ratings of psychosocial risk (e.g., history of mental health problems or abuse, stressful life events, lack of social support), pregnancy-related anxiety, depressive symptomatology, and delusional ideation. RESULTS: There was less delusional ideation during the postpartum period than during early pregnancy. Across all time points, levels of delusional ideation were lower than in the general population. Analyses using multilevel modeling indicated significant fixed-effects for the variables time, age, partnership, being religious and prenatal anxiety, but not depressive symptomatology, on delusional ideation. Immigrant status moderated the effect of psychosocial risk such that greater psychosocial risk predicted more symptoms of delusional ideation among immigrants, but not non-immigrants. CONCLUSION: Psychosocial risk factors place immigrant women at an increased likelihood for experiencing delusional ideation during the perinatal period. PMID- 27670239 TI - D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease. AB - BACKGROUND: Chronic immune diseases, such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals, such as probiotics, for the prevention of allergic disease. However, clinical trials have produced inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host's microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty. OBJECTIVE: We sought to identify and characterize a bioactive probiotic metabolite for potential prevention of allergic airway disease. METHODS: Probiotic supernatants were screened for their ability to concordantly decrease the constitutive CCL17 secretion of a human Hodgkin lymphoma cell line and prevent upregulation of costimulatory molecules of LPS-stimulated human dendritic cells. RESULTS: Supernatants from 13 of 37 tested probiotic strains showed immunoactivity. Bioassay-guided chromatographic fractionation of 2 supernatants according to polarity, followed by total ion chromatography and mass spectrometry, yielded C11H12N2O2 as the molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-tryptophan. In contrast, L-tryptophan and 11 other D-amino acids were inactive. Feeding D-tryptophan to mice before experimental asthma induction increased numbers of lung and gut regulatory T cells, decreased lung TH2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced gut microbial diversity, which was increased by D-tryptophan. CONCLUSIONS: D-tryptophan is a newly identified product from probiotic bacteria. Our findings support the concept that defined bacterial products can be exploited in novel preventative strategies for chronic immune diseases. PMID- 27670240 TI - IFN-gamma orchestrates mesenchymal stem cell plasticity through the signal transducer and activator of transcription 1 and 3 and mammalian target of rapamycin pathways. AB - BACKGROUND: Mesenchymal stem cells (MSCs) display a therapeutic plasticity because of their ability to modulate immunity, foster tissue repair, and differentiate into mesodermal cells. IFN-gamma has been described to differently affect human mesenchymal stem cell (hMSC) and mouse mesenchymal stem cell (mMSC) immunomodulation and differentiation, depending on the inflammatory milieu. OBJECTIVE: We aimed at dissecting the relevant intracellular pathways through which IFN-gamma affects MSC plasticity and the consequence of their manipulation on MSC functions. METHODS: Modification of relevant IFN-gamma-dependent pathways in mMSCs was carried out in vitro through gene silencing or chemical inhibition of key components. Functional outcomes were assessed by means of Western blotting, real-time PCR, differentiation, and proliferation assays on MSCs. The effect on T cells was addressed by T-cell proliferation assays; the effect of mammalian target of rapamycin (mTOR) manipulation in MSCs was studied in vivo in a mouse model of delayed-type hypersensitivity assay. To address whether similar mechanisms are involved also in hMSCs on IFN-gamma stimulation, the effect of chemical inhibition on the same intracellular pathways was assessed by means of Western blotting, and the final outcome on immunomodulatory properties was evaluated based on real-time PCR and T-cell proliferation. RESULTS: We revealed that in mMSCs IFN-gamma-induced immunoregulation is mediated by early phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3, which is significantly enhanced by an extracellular signal-regulated kinase 1/2-dependent mTOR inhibition, thereby promoting pSTAT1 nuclear translocation. Accordingly, after intracellular mTOR inhibition, MSCs augmented their ability to inhibit T-cell proliferation and control delayed-type hypersensitivity in vivo. Similarly, on mTOR blockade, hMSCs also enhanced their immunoregulatory features. A sustained exposure to IFN-gamma led to inhibition of STAT3 activity, which in mMSCs resulted in an impaired proliferation and differentiation. CONCLUSION: These results provide new insights about MSC intracellular pathways affected by IFN-gamma, demonstrating that pharmacologic or genetic manipulation of MSCs can enhance their immunomodulatory functions, which could be translated into novel therapeutic approaches. PMID- 27670242 TI - Dogs, cats, and asthma: Will we ever really know the true risks and benefits? PMID- 27670241 TI - Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69-CD56dim cells. AB - BACKGROUND: In contrast to the extensive knowledge about human natural killer (NK) cells in peripheral blood, relatively little is known about NK cells in the human lung. Knowledge about the composition, differentiation, and function of human lung NK cells is critical to better understand their role in diseases affecting the lung, including asthma, chronic obstructive pulmonary disease, infections, and cancer. OBJECTIVE: We sought to analyze and compare the phenotypic and functional characteristics of NK cells in the human lung and peripheral blood at the single-cell level. METHODS: NK cells in human lung tissue and matched peripheral blood from 132 subjects were analyzed by using 16-color flow cytometry and confocal microscopy. RESULTS: CD56dimCD16+ NK cells made up the vast majority of NK cells in human lungs, had a more differentiated phenotype, and more frequently expressed educating killer cell immunoglobulin like receptors compared with NK cells in peripheral blood. Despite this, human lung NK cells were hyporesponsive toward target cell stimulation, even after priming with IFN-alpha. Furthermore, we detected a small subset of NK cells expressing CD69, a marker of tissue residency. These CD69+ NK cells in the lung consisted predominantly of immature CD56brightCD16- NK cells and less differentiated CD56dimCD16+ NK cells. CONCLUSION: Here, we characterize the major NK cell populations in the human lung. Our data suggest a model in which the majority of NK cells in the human lung dynamically move between blood and the lung rather than residing in the lung as bona fide tissue-resident CD69+ NK cells. PMID- 27670244 TI - Psychostimulant drugs for cocaine dependence. AB - BACKGROUND: Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES: To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy. SEARCH METHODS: This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field. SELECTION CRITERIA: We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants and placebo (RD 0.00, 95% CI -0.01 to 0.01; RD 0.00, 95% CI -0.02 to 0.01, respectively). When we included the type of drug as a moderating variable, the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dexamphetamine than with placebo. Psychostimulants also appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone-maintained, dual heroin-cocaine addicts. Retention to treatment was low, though, so our results may be compromised by attrition bias. We found no evidence of publication bias. AUTHORS' CONCLUSIONS: This review found mixed results. Psychostimulants improved cocaine abstinence compared to placebo in some analyses but did not improve treatment retention. Since treatment dropout was high, we cannot rule out the possibility that these results were influenced by attrition bias. Existing evidence does not clearly demonstrate the efficacy of any pharmacological treatment for cocaine dependence, but substitution treatment with psychostimulants appears promising and deserves further investigation. PMID- 27670245 TI - Self-organised silicide nanodot patterning by medium-energy ion beam sputtering of Si(100): local correlation between the morphology and metal content. AB - We have produced self-organised silicide nanodot patterns by medium-energy ion beam sputtering (IBS) of silicon targets with a simultaneous and isotropic molybdenum supply. Atomic force microscopy (AFM) studies show that these patterns are qualitatively similar to those produced thus far at low ion energies. We have determined the relevance of the ion species on the pattern ordering and properties. For the higher ordered patterns produced by Xe(+) ions, the pattern wavelength depends linearly on the ion energy. The dot nanostructures are silicide-rich as assessed by x-ray photoelectron spectroscopy (XPS) and emerge in height due to their lower sputtering yield, as observed by electron microscopy. Remarkably, a long wavelength corrugation is observed on the surface which is correlated with both the Mo content and the dot pattern properties. Thus, as assessed by electron microscopy, the protrusions are Mo-rich with higher and more spaced dots on their surface whereas the valleys are Mo-poor with smaller dots that are closer to each other. These findings indicate that there is a correlation between the local metal content of the surface and the nanodot pattern properties both at the nanodot and the large corrugation scales. These results contribute to advancing the understanding of this interesting nanofabrication method and aid in developing a comprehensive theory of nanodot pattern formation and evolution. PMID- 27670243 TI - T-bet inhibits innate lymphoid cell-mediated eosinophilic airway inflammation by suppressing IL-9 production. AB - BACKGROUND: Innate lymphoid cells (ILCs) are emerging subsets of immune cells that produce large amounts of cytokines upon cytokine and/or alarmin stimulation. Recent studies have shown that T-bet plays pivotal roles in the development of ILC3s and type 1 ILCs; however, the roles of T-bet in lung type 2 innate lymphoid cells (ILC2s) remain unknown. OBJECTIVE: We sought to determine the role of T-bet in ILC2-mediated airway inflammation. METHODS: The expression of T-bet in lung ILCs (defined as Thy1.2+ Lin- cells) was examined. The roles of T-bet in the development of lung ILC2s and airway inflammation induced by IL-33 administration were examined by using T-bet-deficient (T-bet-/-) mice. Gene expression profiles of T-bet-/- lung ILCs were analyzed by RNA sequencing. RESULTS: T-bet was expressed in lung ILC2s (defined as Thy1.2+ Lin- cells expressing ST2 or CD25) and IFN-gamma enhanced its expression. Although the development of lung ILC2s at steady-state conditions was normal in T-bet-/- mice, IL-33-induced accumulation of lung ILC2s and eosinophilic airway inflammation were exacerbated in T-bet-/- mice. The exacerbated accumulation of ILC2s and eosinophilic airway inflammation by the absence of T-bet were evident even in a RAG2-/- background, suggesting that T-bet expressed in non-T/non-B population is involved in the suppression of IL-33-induced eosinophilic airway inflammation. Transcriptome analysis revealed that IL-9 expression in IL-33-stimulated lung ILCs was upregulated in T-bet-/- mice compared with that in wild-type mice. Importantly, neutralization of IL-9 markedly attenuated IL-33-induced accumulation of lung ILC2s and eosinophilic inflammation in T-bet-/- mice. CONCLUSIONS: T-bet suppresses IL-9 production from lung ILC2s and thereby inhibits IL-33-induced eosinophilic airway inflammation. PMID- 27670246 TI - Managing extremes of assessor judgment within the OSCE. AB - CONTEXT: There is a growing body of research investigating assessor judgments in complex performance environments such as OSCE examinations. Post hoc analysis can be employed to identify some elements of "unwanted" assessor variance. However, the impact of individual, apparently "extreme" assessors on OSCE quality, assessment outcomes and pass/fail decisions has not been previously explored. This paper uses a range of "case studies" as examples to illustrate the impact that "extreme" examiners can have in OSCEs, and gives pragmatic suggestions to successfully alleviating problems. METHOD AND RESULTS: We used real OSCE assessment data from a number of examinations where at station level, a single examiner assesses student performance using a global grade and a key features checklist. Three exemplar case studies where initial post hoc analysis has indicated problematic individual assessor behavior are considered and discussed in detail, highlighting both the impact of individual examiner behavior and station design on subsequent judgments. CONCLUSIONS: In complex assessment environments, institutions have a duty to maximize the defensibility, quality and validity of the assessment process. A key element of this involves critical analysis, through a range of approaches, of assessor judgments. However, care must be taken when assuming that apparent aberrant examiner behavior is automatically just that. PMID- 27670248 TI - Discrimination of Axial and Central Stereogenic Elements in Chiral Bis(oxazolines) Based on Atropisomeric 3,3'-Bithiophene Scaffolds Through Chiroptical Spectroscopies. AB - Two diastereoisomeric pairs of bis-oxazolines, provided with a stereogenic center at carbon 4 and based on the 3,3'-bithiophene atropisomeric scaffold, were synthesized and structurally characterized. They differ in the substituents at positions 2 and 5 of the thiophene rings, which are functionalized with methyl (1) or phenyl (2) groups, respectively. In vibrational circular dichroism (VCD) spectra, recorded in CCl4 solutions, it is possible to distinctly recognize the characteristic features of axial and central stereogenic elements. In tandem with Density Functional Theory (DFT) calculations, the absolute configuration (AC) of the diastereoisomers was safely established. In this case, VCD was shown to be superior to ECD (electronic circular dichroism) in the assignment of AC. The normal modes, evaluated from DFT calculations, show that the VCD signals in correspondence with the stereogenic axis of the bithiophene unit are different for 1 and 2. The VCD spectra of a molecular analog of 1, the (S)-2,2',5,5' tetramethyl-4,4'-bis-(diphenylphosphino)-3,3'-bithiophene oxide (3), characterized by the same 3,3'-bithiophene scaffold, but devoid of stereogenic centers, exhibits signals similar to those observed in the case of diastereoisomer (aS,R,R)-1a, associated with almost identical normal modes. Chirality 28:686-695, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27670247 TI - Human Tear Fluid Reduces Culturability of Contact Lens-Associated Pseudomonas aeruginosa Biofilms but Induces Expression of the Virulence-Associated Type III Secretion System. AB - PURPOSE: The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens (CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression. METHODS: P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured by RT-qPCR. Controls included trypticase soy broth, PBS and planktonic bacteria. RESULTS: With or without tear fluid, biofilms grew to ~108 CFU viable bacteria by 24 h. Exposing biofilms to tear fluid after they had formed without it on lenses reduced bacterial culturability ~180-fold (P<.001). CL growth increased T3SS gene expression versus planktonic bacteria [5.46 +/- 0.24-fold for T3SS transcriptional activitor exsA (P=.02), and 3.76 +/- 0.36-fold for T3SS effector toxin exoS (P=.01)]. Tear fluid further enhanced exsA and exoS expression in CL-grown biofilms, but not planktonic bacteria, by 2.09 +/- 0.38 fold (P=.04) and 1.89 +/- 0.26-fold (P<.001), respectively. CONCLUSIONS: Considering the pivitol role of the T3SS in P. aeruginosa infections, its induction in CL-grown P. aeruginosa biofilms by tear fluid might contribute to the pathogenesis of CL-related P. aeruginosa keratitis. PMID- 27670249 TI - Circularly Polarized Luminescence: A Review of Experimental and Theoretical Aspects. AB - We review the present status of experiments and calculations for circularly polarized luminescence (CPL) of simple organic molecules and of stimuli responsive organic molecules. Together with the historical report of the main instrumental approaches, a few crucial points about experiments are tackled, with the aim of defining measurement protocols, in view of the wide availability of commercial apparatuses in the near future. The calculations aimed at interpreting the CPL spectra, mostly based on time-dependent Density Functional Theory (TD DFT) calculations, which started around 2010, are reviewed, limiting the discussion to small to mid-sized molecules. Some applications of CPL spectra of organic molecules-based systems are presented, with a focus especially on two fields: material science and biology. Chirality 28:696-707, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27670250 TI - Phase Angle and Impedance Ratio: Reference Cut-Points From the United States National Health and Nutrition Examination Survey 1999-2004 From Bioimpedance Spectroscopy Data. AB - BACKGROUND: Raw bioimpedance parameters (eg, 50-kHz phase angle [PA] and 200 kHz/5-kHz impedance ratio [IR]) have been investigated as predictors of nutrition status and/or clinical outcomes. However, their validity as prognostic measures depends on the availability of appropriate reference data. Using a large and ethnically diverse data set, we aimed to determine if ethnicity influences these measures and provide expanded bioimpedance reference data for the U.S. POPULATION: METHODS: The National Health and Nutrition Examination Survey (NHANES) is an ongoing compilation of studies conducted by the U.S. Centers for Disease Control and Prevention designed to monitor nutrition status of the U.S. POPULATION: The NHANES data sets analyzed were from the years 1999-2000, 2001 2002, and 2003-2004. RESULTS: Multivariate analysis showed that PA and IR differed by body mass index (BMI), age, sex, and ethnicity (n = 6237; R2 = 41.2%, P < .0001). Suggested reference cut-points for PA stratified by age decade, ethnicity, and sex are provided. CONCLUSION: Ethnicity is an important variable that should be accounted for when determining population reference values for PA and IR. We have provided sex-, ethnicity-, and age decade-specific reference values from PA for use by future studies in U.S. POPULATIONS: Interdevice differences are likely to be important contributors to variability across published population-specific reference data and, where possible, should be evaluated in future research. Ultimately, further validation with physiologically relevant reference measures (eg, dual-energy x-ray absorptiometry) is necessary to determine if PA/IR are appropriate bedside tools for the assessment of nutrition status in a clinical population. PMID- 27670251 TI - In vivo MR imaging with simultaneous RF transmission and reception. AB - PURPOSE: To present a practical scheme of a simultaneous radiofrequency (RF) transmit (Tx) and receive (Rx) (STAR) system for MRI, discuss the challenges and solutions, and show preliminary in vivo MR images obtained with this new technique. METHODS: A remotely controlled STAR system was built and tested with a transverse electromagnetic head coil on a 4T (Oxford, 90 cm-bore) MRI scanner equipped with an Agilent DirectDrive console (Agilent, Santa Clara, CA). In vivo head images have been acquired using continuous sweep excitation and acquisition. RESULTS: The bench test and MR experimental results show our STAR system to have high isolation (60 dB) between Tx and Rx, with insensitivity to load swings created by head motion. To acquire in vivo head images, ultralow RF peak power of 50 mW was used. CONCLUSION: A novel motion-insensitive STAR MRI technique was developed and experimentally tested. The first in vivo MR images using this method were acquired. Magn Reson Med 76:1932-1938, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27670252 TI - Estimates of the actual relationship between half-sibs in a pig population. AB - Genomic relationships based on markers capture the actual instead of the expected (based on pedigree) proportion of genome shared identical by descent (IBD). Several methods exist to estimate genomic relationships. In this research, we compare four such methods that were tested looking at the empirical distribution of the estimated relationships across 6704 pairs of half-sibs from a cross-bred pig population. The first method based on multiple marker linkage analysis displayed a mean and standard deviation (SD) in close agreement with the expected ones and was robust to changes in the minor allele frequencies (MAF). A single marker method that accounts for linkage disequilibrium (LD) and inbreeding came second, showing more sensitivity to changes in the MAF. Another single marker method that considers neither inbreeding nor LD showed the smallest empirical SD and was the most sensible to changes in MAF. A higher mean and SD were displayed by VanRaden's method, which was not sensitive to changes in MAF. Therefore, the method based on multiple marker linkage analysis and the single marker method that considers LD and inbreeding performed closer to theoretical values and were consistent with the estimates reported in literature for human half-sibs. PMID- 27670254 TI - Cardiorespiratory fitness cut points to avoid cardiovascular disease risk in children and adolescents; what level of fitness should raise a red flag? A systematic review and meta-analysis. AB - BACKGROUND: Poor cardiorespiratory fitness is associated with cardiovascular disease risk factors. AIM: To perform a systematic review and meta-analysis of the relationship between poor cardiorespiratory fitness and cardiovascular disease risk in children and adolescents. METHODS: Systematic literature search (1980 to 11 April 2015) for studies that determined a cardiorespiratory fitness cut point that predicted cardiovascular disease risk in children and adolescents. RESULTS: We identified 7 studies that included 9280 children and adolescents (49% girls) aged 8-19 years from 14 countries. Cardiovascular disease risk was already present in boys (6-39%) and girls (6-86%). Boys with low fitness (<41.8 mL/kg/min) had a 5.7 times greater likelihood of having cardiovascular disease risk (95% CI 4.8 to 6.7). The comparable diagnostic OR for girls with low fitness (<34.6 mL/kg/min) was 3.6 (95% CI 3.0 to 4.3). The 95% confidence region of cardiorespiratory fitness associated with low cardiovascular disease risk ranges, 41.8-47.0 mL/kg/min in boys (eg, stages 6-8 for a boy aged 15 years) and 34.6 39.5 mL/kg/min in girls (eg, stages 3-5 for a girl aged 15 years). The cardiorespiratory fitness cut point to avoid cardiovascular disease risk ranged 41.8 mL/kg/min in boys and was 34.6 mL/kg/min in girls. SUMMARY: Fitness levels below 42 and 35 mL/kg/min for boys and girls, respectively, should raise a red flag. These translate to 6 and 3 stages on the shuttle run test for a boy and a girl, both aged 15 years, respectively. These cut points identify children and adolescents who may benefit from primary and secondary cardiovascular prevention programming. PMID- 27670253 TI - Cell-free synthesis of functional human epidermal growth factor receptor: Investigation of ligand-independent dimerization in Sf21 microsomal membranes using non-canonical amino acids. AB - Cell-free protein synthesis systems represent versatile tools for the synthesis and modification of human membrane proteins. In particular, eukaryotic cell-free systems provide a promising platform for their structural and functional characterization. Here, we present the cell-free synthesis of functional human epidermal growth factor receptor and its vIII deletion mutant in a microsome containing system derived from cultured Sf21 cells. We provide evidence for embedment of cell-free synthesized receptors into microsomal membranes and asparagine-linked glycosylation. Using the cricket paralysis virus internal ribosome entry site and a repetitive synthesis approach enrichment of receptors inside the microsomal fractions was facilitated thereby providing analytical amounts of functional protein. Receptor tyrosine kinase activation was demonstrated by monitoring receptor phosphorylation. Furthermore, an orthogonal cell-free translation system that provides the site-directed incorporation of p azido-L-phenylalanine is characterized and applied to investigate receptor dimerization in the absence of a ligand by photo-affinity cross-linking. Finally, incorporated azides are used to generate stable covalently linked receptor dimers by strain-promoted cycloaddition using a novel linker system. PMID- 27670255 TI - Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system. AB - OBJECTIVE: To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). METHODS: We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with kappa statistics. RESULTS: Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (kappa value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. CONCLUSION: To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID- 27670256 TI - Fertility preserving treatment with hysteroscopic resection followed by progestin therapy in young women with early endometrial cancer. AB - OBJECTIVE: To report our 15-year institutional experience of fertility-sparing treatment in young patients with early endometrial cancer (EC) treated by combined hysteroscopic resection and progestin therapy. METHODS: Twenty-eight patients (stage IA, G1 and 2 endometrioid EC) wishing to preserve their fertility were enrolled into this prospective study. Hysteroscopic resection was used to resect the tumor, endometrium adjacent to the tumor and myometrium underlying the tumor. Adjuvant hormonal therapy consisted of oral megestrol acetate or levonorgestrel intrauterine device for 6 months or more. RESULTS: After 3 months from the progestin start date, 25 patients (89.3%) showed a complete regression (median time to complete regression, 3 months [range, 3-9 months]), two (7.1%) showed persistent disease, while one patient (3.6%) presented with progressive disease and underwent definitive surgery (stage IA, G3 endometrioid). At 6 months, one of the two patients with persistent disease underwent definitive surgery (stage IA, G1 endometrioid), while the other one was successfully re treated. Two recurrences were observed (7.7%) both involving the endometrium and synchronous ovarian cancer. The median duration of complete response was 94.5 months (range, 8-175 months). More than half of the responders (57.7%) attempted to conceive with 93.3% and 86.6% pregnancy and live birth rates, respectively. CONCLUSION: The addition of a standardized three-step resectoscopy to progestin would seem to improve the efficacy of progestin alone. High pregnancy and live birth rates were observed in women attempting to conceive. PMID- 27670257 TI - Pathologic findings at risk-reducing salpingo-oophorectomy (RRSO) in germline BRCA mutation carriers with breast cancer: significance of bilateral RRSO at the optimal age in germline BRCA mutation carriers. AB - OBJECTIVE: Most BRCA1/2 carriers do not undergo risk-reducing salpingo oophorectomy (RRSO) by the recommended age. This study aimed to find the incidence of precursor lesions and cancer after RRSO. METHODS: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2010 to 2014. From 2013, all cases were examined according to the Sectioning and Extensively Examining the Fimbria (SEE/FIM) protocol and underwent immunohistochemically staining. RRSO was performed in 63 patients, 27 in 2010 to 2012 and 36 in 2013 to 2014. RESULTS: The median age at RRSO was 46.5 years (range, 32 to 73 years). Occult invasive cancer was detected in eight patients, of ovarian origin in five and of tubal origin in three. All occult invasive cancer cases with metastasis were detected in patients older than 40 years. Of the 36 patients from the 2013 to 2014 cohort, seven showed p53 overexpression, one showed Ki-67 overexpression, two showed serous tubal intraepithelial carcinoma, and three showed occult cancer. The detection rate of precursor lesions or cancer was 36.1% (13/36). In the analysis according to age, precursor lesions were more common in BRCA1 mutation carriers younger than 40 years old (66.7% vs. 20.0%). In BRCA2 mutation carriers, precursor lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of precursor lesions in BRCA1 mutation carriers. CONCLUSION: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers. PMID- 27670258 TI - Genetic screening in young women diagnosed with endometrial cancer. AB - OBJECTIVE: To evaluate the importance of Lynch syndrome associated risk screening in the patients aged less than 50 years affected from endometrial cancer. METHODS: From 2007 to 2014, 41 patients affected from endometrial cancer and aged less than 50 years underwent surgery at the Complex Operative Unit of Gynecology and Obstetrics, Cannizzaro Hospital of Catania, Italy. They were selected to undergo mismatch repair gene mutation analysis using immunohistochemistry (IHC; four markers: MLH1, MSH2, MSH6, PMS2) and microsatellite instability (MSI) test. For samples that resulted negative to IHC (abnormal finding), MSI test was performed to further study the suspected mutation. Samples were classified as MSI high (MSI-H) if more than one marker was identified as unstable; MSI-low (MSI-L) if only one marker was identified as unstable; or MSI-stable (MSI-S) if no marker was identified as unstable. Samples were subdivided into two groups: MSI-H/L and MSI-S. Statistical analysis was performed to assess differences regarding survival, tumor staging, grading, and invasion of lymphovascular space between these two groups. RESULTS: IHC analysis showed that in 46% (19/41) of samples there was negative outcome. Forty-two percent (8/19) of these negative samples were unstable (either low or high). Of eight patients showing MSI, 75% were MSI L, while 25% were MSI-H. Differences in survival, stage, grade, lymphovascular space invasion and Amsterdam criteria adherence were not statistically significant due to the small size of the cohort. CONCLUSION: IHC and MSI test results of our cohort lead us to assess the relevance of performing Lynch syndrome genetic screening in endometrial cancer patients aged less than 50 years at the time of diagnosis. PMID- 27670259 TI - Surgical manual of the Korean Gynecologic Oncology Group: classification of hysterectomy and lymphadenectomy. AB - The Surgery Treatment Modality Committee of the Korean Gynecologic Oncologic Group (KGOG) has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we focused on radical hysterectomy and lymphadenectomy, and we developed a KGOG classification for those conditions. PMID- 27670260 TI - Surgical manual of the Korean Gynecologic Oncology Group: ovarian, tubal, and peritoneal cancers. AB - The Surgery Treatment Modality Committee of the Korean Gynecologic Oncology Group has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we describe surgical procedure for ovarian, fallopian tubal, and peritoneal cancers. PMID- 27670261 TI - Perioperative changes in serum CA125 levels: a prognostic factor for disease specific survival in patients with ovarian cancer. AB - OBJECTIVE: In patients with advanced stage epithelial ovarian cancer (EOC) the volume of residual tumor after debulking is known as prognostic factor for survival. We wanted to examine the relationship between postoperative decline in serum CA125 and residual disease after cytoreductive surgery and evaluate perioperative changes in serum CA125 levels as predictor for disease-specific survival. METHODS: A retrospective study was conducted of patients with FIGO stage IIb-IV EOC treated with cytoreductive surgery, followed by chemotherapy between 1996 and 2010 in three hospitals in the Southeastern region of the Netherlands. Data were analyzed with the use of multilevel linear regression and Cox-proportional hazard regression models. RESULTS: A postoperative decline in serum CA125 level of >=80% was associated with complete primary cytoreduction (p=0.035). Univariate analyses showed favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction. In multivariate analyses the decline in serum CA125 but not the outcome of surgery remained significantly associated with better survival (HR(50% 79%)=0.52 [95% CI: 0.28-0.96] and HR(>=80%)=0.26 [95% CI: 0.13-0.54] vs. the serum CA125 decline of <50% [p<0.001]). CONCLUSION: The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons' estimation of residual tumor volume. PMID- 27670262 TI - Novel mononuclear Pt2+ and Pd2+ complexes containing (2,3 f)pyrazino(1,10)phenanthroline-2,3-dicarboxylic acid as a multi-donor ligand. Synthesis, structure, interaction with DNA, in vitro cytotoxicity, and apoptosis. AB - New cytotoxic, mononuclear Pt and Pd coordination complexes featuring the planar, multi-donor ligand (2,3-f)pyrazino(1,10)phenanthroline-2,3-dicarboxylic acid (H2PPDA) have been synthesized under hydrothermal conditions (in water, at high temperature and pressure) and fully characterized. The complexes were proven to be isostructural by applying the single-crystal X-ray diffraction technique. UV Vis and fluorescence spectroscopy investigations on their interaction with fish sperm DNA revealed a considerable binding capacity while gel electrophoresis provided evidence in favor of cleavage of pBR322 plasmid DNA. The newly synthesized complexes manifested significant in vitro cytotoxic activity against two different human cancer cell lines, the KB and JEKO cells, with cell death mainly caused by apoptosis. PMID- 27670263 TI - Water-in-Supercritical CO2 Microemulsion Stabilized by a Metal Complex. AB - Herein we propose for the first time the utilization of a metal complex for forming water-in-supercritical CO2 (scCO2 ) microemulsions. The water solubility in the metal-complex-stabilized microemulsion is significantly improved compared with the conventional water-in-scCO2 microemulsions stabilized by hydrocarbons. Such a microemulsion provides a promising route for the in situ CO2 reduction catalyzed by a metal complex at the water/scCO2 interface. PMID- 27670264 TI - A strategy to expeditious invasive treatment improves clinical outcome in comatose patients with aneurysmal subarachnoid haemorrhage. AB - BACKGROUND: In patients with poor clinical condition after aneurysmal subarachnoid haemorrhage (aSAH), treatment is often deferred until patients show signs of improvement. Early external ventricular drainage and aneurysm occlusion may improve prognosis also in poor grade patients. The clinical outcome of an expeditious approach was compared with that of a conservative approach. METHODS: In all, 285 consecutive World Federation of Neurological Surgeons (WFNS) grade V aSAH patients admitted to three university hospitals between January 2000 and June 2007 were included. Two hospitals followed an expeditious approach, one a more conservative approach. Groups were compared with respect to demographic and clinical characteristics and outcome. Univariable and multivariable analyses were performed to determine the associations with good outcome (Glasgow Outcome Scale scores 4-5), using logistic regression models. RESULTS: Good outcome was seen more often in expeditiously treated patients [22% vs. 11%; odds ratio (OR) 2.24, 95% confidence interval (CI) 1.17-4.27]. Expeditiously treated patients more often underwent aneurysm occlusion than conservatively treated patients (64% vs. 27%; OR 4.86, 95% CI 2.93-8.05) and placement of an external ventricular catheter (82% vs. 31%; OR 10.05, CI 5.72-10.66). There was no significant difference in rebleeding between patient groups. Occlusion of the aneurysm was the only variable that remained significant in the multivariable model with an OR of 43.73 (95% CI 10.34-184.97). CONCLUSIONS: An expeditious invasive treatment strategy in WFNS grade V aSAH patients can lead to a better outcome. Hesitance in the early stages seems a self-fulfilling prophecy for a poor outcome. PMID- 27670265 TI - Vision in the common bed bug Cimex lectularius L. (Hemiptera: Cimicidae): eye morphology and spectral sensitivity. AB - Bed bugs as pests of public health importance recently experienced a resurgence in populations throughout the U.S. and other countries. Consequently, recent research efforts have focused on improving understanding of bed bug physiology and behaviour to improve management. While few studies have investigated the visual capabilities of bed bugs, the present study focused specifically on eye morphology and spectral sensitivity. A 3-D imaging technique was used to document bed bug eye morphology from the first instar through adult and revealed morphological characteristics that differentiate the common bed bug from the tropical bed bug as well as sex-specific differences. Electrophysiological measurements were used to evaluate the spectral sensitivity of adult bed bugs. Male bed bugs were more responsive than females at some wavelengths. Electrophysiological studies provided evidence for at least one photoreceptor with a spectral sensitivity curve peak in the green (lambdamax 520 nm) region of the spectrum. The broadened long wavelength portion of the spectral sensitivity curve may potentially indicate another photoreceptor in the yellow-green (lambdamax 550 nm) portion of the spectrum or screening pigments. Understanding more about bed bug visual biology is vital for designing traps, which are an important component of integrated bed bug management. PMID- 27670266 TI - TEX13 is a novel male germ cell-specific nuclear protein potentially involved in transcriptional repression. AB - The identification and characterization of male germ cell-specific genes is crucial to understanding the mechanisms of male germ cell development. In this study, we investigated the protein encoded by the novel mouse germ cell-specific gene testis-expressed gene 13 (Tex13). We found that TEX13 expression is testis- and germ cell-specific and is regulated in a stage-specific manner via translational repression. Immunostaining of testicular cells and sperm showed that TEX13 is localized in the nuclei of spermatogenic cells and the redundant nuclear envelope of mature sperm. Remarkably, we found that TEX13 possesses transcriptional repressor activity and that its overexpression in GC-2 cells altered the expression levels of 130 genes. Our results suggest that TEX13 has a potential role in transcriptional regulation during spermatogenesis. PMID- 27670267 TI - The CLOCK trial, a double-blinded randomized controlled trial: Trisodium citrate 30% and minocycline 3 mg/mL plus EDTA 30 mg/mL are effective and safe for catheter patency maintenance among CKD 5D patients on hemodialysis. AB - INTRODUCTION: Poor blood flow rate (PF) is highly prevalent among CKD 5D patients with long-term central venous catheters. Heparin catheter lock solutions are commonly used to maintain catheter patency, however the incidence of PF remains high. The purpose of the CLOCK Trial was to evaluate two catheter lock solutions on reduction of PF incidence. METHODS: Seventy-five CKD 5D patients on high efficiency hemodialysis at the Integrated Centre of Nephrology (Guarulhos, Brazil) were randomized 1:1:1 to receive a lock solution combining minocycline 3 mg/mL with the anticoagulant/chelation agent EDTA 30 mg/mL (M-EDTA) or heparin 1000 IU/mL (H) or trisodium citrate 30% (TSC) vs. Hfor 15 weeks. A total of 68 patients completed the trial in which both investigators and patients were blinded to treatment allocation. The primary end-point was the occurrence of hydraulic resistance and secondary safety end-point was adverse drug reactions related to the lock solutions. FINDINGS: At the beginning of the trial, 7 patients were excluded from this trial due to their poor catheter care. The incidence of hydraulic resistance was significantly higher among patients on H (18/23) compared to TSC (4/22) and M-EDTA (2/23) lock solutions, (P < 0.001). DISCUSSION: The CLOCK Trial suggests TSC and M-EDTA may preserve catheter patency better than H. TSC may be a better option due the lack of association with long term antimicrobial resistance. PMID- 27670268 TI - Effect of silybin on the fibrillation of hen egg-white lysozyme. AB - In this study, the fibrillation of hen egg-white lysozyme (HEWL) in the absence and presence of different concentrations of silybin was studied by thioflavin T spectroscopy, Congo red binding assays, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence assay, circular dichroism, and transmission electron microscopy. The experimental results indicated that not only the fibrillation of HEWL at high temperature (65 degrees C) and low pH (pH = 2.0) could be inhibited effectively by silybin but also the inhibition of HEWL by silybin followed a dose dependent manner. Molecular docking studies indicated that 2 possible binding modes could be found in the interaction between silybin and HEWL via van der Waals forces and electrostatic forces as well as hydrogen bonding. One of these 2 conformations was directly entered into the cavity of HEWL (binding site I); the other was bound to the surface of HEWL (binding site II). In this way, silybin could not only increase the hydrophobicity of the cavity or the surface of HEWL but also influence the microenvironment of the binding site, which was able to stabilize the structure of HEWL and delay the process of HEWL fibrosis. PMID- 27670269 TI - Primary Breast Cancer Tumor and Patient Characteristics as Predictors of Adjuvant Radiation Therapy. AB - Adjuvant radiation therapy reduces the risk of local recurrence of breast cancer. Our study identifies patient and tumor characteristics that guide the use of adjuvant radiation therapy and evaluates our adherence to recommended guidelines. A retrospective review was undertaken of 1,667 stage I-III breast cancer patients treated at a regional cancer center from 2004 to 2007. Univariate analysis was used to select factors for entry into a multivariate stepwise logistic regression model. Descriptive statistics was used to compare use of radiation therapy of 382 stage I-III breast cancer patients diagnosed in 2013 to those from 2004 to 2007. The primary indicators for any radiation therapy (n = 935) were breast conserving surgery (OR 79.5, 95% CI [47.6-132.9]), four to nine positive lymph nodes (71.9, [17.0-304.7]), and greater than nine positive lymph nodes (60.5, [7.9-460.8]). In post-mastectomy patients (n = 408), the indicators for radiation therapy were four to nine positive lymph nodes (29.4, [12.9-67.4]) and greater than nine positive lymph nodes (108.3, [14.5-807.5]). In breast conserving surgery patients (n = 1,081) 96.1% were offered radiation therapy. Patients offered local-regional radiation therapy were more likely to have any positive nodes (ORs 4.3-91.0), have had a mastectomy (4.3, [2.2-8.4]), and had larger tumors (1.6, [1.3-2.0]). Local-regional radiation therapy was recommended less frequently in node positive patients in 2004-2007 (35.0%) compared to in 2013 (70.5%) [p < 0.001]. Patients who had a breast conserving surgery or had four or more positive lymph nodes were more likely to receive radiation therapy. Patients with any positive lymph nodes, larger tumors, or who had a mastectomy were more likely to receive local-regional radiation therapy. Our institution was more likely to offer local-regional radiation therapy in node positive breast cancer in 2013 compare to 2004-2007. PMID- 27670270 TI - Development and Preliminary Psychometric Evaluation of Decisional Balance and Self-Efficacy Measures for Managing Anxiety in a National Sample of Clinically Anxious Adults. AB - PURPOSE: Anxiety is the most common and costly mental illness in the United States. Reducing avoidance is a core element of evidence-based treatments. Past research shows readiness to address avoidance affects outcomes. Investigating avoidance from a transtheoretical model (TTM) perspective could facilitate tailored approaches for individuals with low readiness. This study developed and examined psychometric properties of TTM measures for addressing anxiety-based avoidance. DESIGN: Cross-sectional survey. SETTING: Community centers, online survey. PARTICIPANTS: Five hundred ninety-four individuals aged 18 to 70 with clinically significant anxiety. MEASURES: Overall Anxiety Severity Questionnaire, stages of change, decisional balance, and self-efficacy. ANALYSIS: The sample was randomly split into halves for principal component analyses (PCAs) and confirmatory factor analyses (CFAs) to test measurement models. Further analyses examined relationships between constructs. RESULTS: For decisional balance, PCA indicated two 5-item factors (pros and cons). Confirmatory factor analysis supported a 2-factor correlated model, Satorra-Bentler scaled chi-square [Formula: see text], comparative fit index (CFI = 0.94), root mean square error of approximation (RMSEA = 0.07), pros: alpha = 0.87, rho = 0.87, cons: alpha = 0.75, and rho = 0.75. For self-efficacy, PCA indicated one 6-item factor supported by CFA, [Formula: see text], P < .01, CFI = 0.98, RMSEA = 0.09, alpha = 0.90, rho = 0.87. As hypothesized, significant cross-stage differences were observed for pros and self-efficacy, and significant relationships between anxiety severity and pros, cons, and self-efficacy were found. CONCLUSION: Findings show strong psychometric properties and support the application of a readiness-based model to anxiety. In contrast to findings of other behaviors, cons remain high in action and maintenance. These measures provide a solid empirical foundation to develop TTM-tailored interventions to enhance engagement in treatment. PMID- 27670271 TI - Bt Cry1Ie Toxin Does Not Impact the Survival and Pollen Consumption of Chinese Honey Bees, Apis cerana cerana (Hymenoptera, Apidae). AB - The cry1Ie gene may be a good candidate for the development of Bt maize because over-expression of Cry1Ie is highly toxic to Lepidopteran pests such as Heliothis armigera Hubner and Ostrinia furnacalis Guenee. The Bt cry1Ie gene also has no cross resistance with other insecticidal proteins such as Cry1Ab, Cry1Ac, Cry1Ah, or Cry1F. Chinese honey bees (Apis cerana cerana) are potentially exposed to insect-resistant genetically modified (IRGM) crops expressing Cry1Ie toxin via the collection of IRGM crop pollen. In this study, we tested whether Chinese honey bee workers are negatively affected by sugar syrup containing 20, 200, or 20,000 ng/ml Cry1Ie toxin and 48 ng/ml imidacloprid under controlled laboratory conditions. Our results demonstrated that the Cry1Ie toxin does not adversely impact survival and pollen consumption of Chinese honey bees. However, imidacloprid decreases Chinese honey bee survival and the total pollen consumption on the 5th, 6th, and 18th d of exposure. The described bioassay is suitable to assess the effects of GM expressed toxins against honey bee. PMID- 27670272 TI - Layer-specific femorotibial cartilage T2 relaxation time in knees with and without early knee osteoarthritis: Data from the Osteoarthritis Initiative (OAI). AB - Magnetic resonance imaging (MRI)-based spin-spin relaxation time (T2) mapping has been shown to be associated with cartilage matrix composition (hydration, collagen content &orientation). To determine the impact of early radiographic knee osteoarthritis (ROA) and ROA risk factors on femorotibial cartilage composition, we studied baseline values and one-year change in superficial and deep cartilage T2 layers in 60 subjects (age 60.6 +/- 9.6 y; BMI 27.8 +/- 4.8) with definite osteophytes in one knee (earlyROA, n = 32) and with ROA risk factors in the contralateral knee (riskROA, n = 28), and 89 healthy subjects (age 55.0 +/- 7.5 y; BMI 24.4 +/- 3.1) without signs or risk factors of ROA. Baseline T2 did not differ significantly between earlyROA and riskROA knees in the superficial (48.0 +/- 3.5 ms vs. 48.1 +/- 3.1 ms) or the deep layer (37.3 +/- 2.5 ms vs. 37.3 +/- 1.8 ms). However, healthy knees showed significantly lower superficial layer T2 (45.4 +/- 2.3 ms) than earlyROA or riskROA knees (p <= 0.001) and significantly lower deep layer T2 (35.8 +/- 1.8 ms) than riskROA knees (p = 0.006). Significant longitudinal change in T2 (superficial: 0.5 +/- 1.4 ms; deep: 0.8 +/- 1.3 ms) was only detected in healthy knees. These results do not suggest an association of early ROA (osteophytes) with cartilage composition, as assessed by T2 mapping, whereas cartilage composition was observed to differ between knees with and without ROA risk factors. PMID- 27670273 TI - Could Bat Cell Temperature and Filovirus Filament Length Explain the Emergence of Ebola Virus in Mammals? Predictions of a Thermodynamic Model. AB - The host reservoir of Zaire ebolavirus (EBOV) remains elusive. One suggestion is that EBOV emerges in mammals when the precursor virus jumps from mayflies (or other riverine insects) to insectivorous bats. However, this does not fit with the current view that filoviruses cannot infect arthropods. Here, it is first argued that the evidence that arthropods are refractory is not definitive. Second, it is proposed that a combination of filovirus filament length and the high temperature (~42 degrees C) experienced by an insect virus ingested by a flying bat, together with the large number of insects eaten by bats (e.g. during an ephemeral mass emergence of mayflies), facilitate jumping the species barrier. The length of a filovirus filament is related to the number of genome copies (GC). Predictions from a preliminary thermodynamic model developed here suggest that filament length could greatly affect EBOV infectivity to mammalian cells with infectivity peaking for filaments of a certain length. Importantly, the infectivity to mammals of even short filaments may be more than one million-fold higher than that for the single GC virion. Third, it is proposed that at the high temperature within the bat, the phospholipid phosphatidylserine in the virus envelope promotes filament formation through fusion of single GC particles within the ingested insect, thus hugely increasing their infectivity to bats. Forth, according to the thermodynamic model, increasing the temperature from 27 degrees C (insect cell temperature at average air temperature in Guinea, West Africa) to 42 degrees C (bat) could increase the affinity of the filaments for bat cells by 1-2 orders of magnitude, while having no effect on the binding affinity of the single GC virions. The thermodynamic model developed here is supported by the counterintuitive observation that high glycoprotein densities on the EBOV surface reduce its infectivity in contrast to other viruses such as HIV. PMID- 27670275 TI - Shear banding in nematogenic fluids with oscillating orientational dynamics. AB - We investigate the occurrence of shear banding in nematogenic fluids under planar Couette flow, based on mesoscopic dynamical equations for the orientational order parameter and the shear stress. We focus on parameter values where the sheared homogeneous system exhibits regular oscillatory orientational dynamics, whereas the equilibrium system is either isotropic (albeit close to the isotropic-nematic transition) or deep in its nematic phase. The numerical calculations are restricted to spatial variations in shear gradient direction. We find several new types of shear-banded states characterized by regions with regular oscillatory orientational dynamics. In all cases shear banding is accompanied by a non monotonicity of the flow curve of the homogeneous system; however, only in the case of the initially isotropic system this curve has the typical S-like shape. We also analyze the influence of different orientational boundary conditions and of the spatial correlation length. PMID- 27670278 TI - Awards from the Society for Pediatric Radiology and the European Society of Paediatric Radiology at the 2016 International Pediatric Radiology 7(th) Conjoint Meetingand Exhibition. PMID- 27670274 TI - 8-C-(E-phenylethenyl)quercetin from onion/beef soup induces autophagic cell death in colon cancer cells through ERK activation. AB - SCOPE: Quercetin, a flavonoid, widely distributed in edible fruits and vegetables, was reported to effectively inhibit 2-amino-1-methyl-6 phenylimidazo[4, 5-b]pyridine (PhIP) formation in a food model (roast beef patties) with itself being converted into a novel compound 8-C-(E phenylethenyl)quercetin (8-CEPQ). Here we investigated whether 8-CEPQ could be formed in a real food system, and tested its anticancer activity in human colon cancer cell lines. METHODS AND RESULTS: LC-MS was applied for the determination of 8-CEPQ formation in onion/beef soup. Anticancer activity of 8-CEPQ was evaluated by using cell viability assay and flow cytometry. Results showed that 8 CEPQ suppressed proliferation and caused G2 phase arrest in colon cancer cells. Based on immunofluorescent staining assay, western blot assay, and RNA knockdown data, we found that 8-CEPQ did not cause apoptotic cell death. Instead, it induced autophagic cell death. Moreover, treatment with 8-CEPQ induced phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of ERK phosphorylation by the mitogen-activated protein kinase kinase (MEK)/ERK inhibitor U0126 attenuated 8-CEPQ-induced autophagy and reversed 8-CEPQ-mediated cell growth inhibition. CONCLUSION: Our results demonstrate that 8-CEPQ, a novel quercetin derivative, could be formed in onion/beef soup. 8-CEPQ inhibited colon cancer cell growth by inducing autophagic cell death through ERK activation. PMID- 27670279 TI - Blockade of the renin-angiotensin system prevents acute and immunologically relevant colitis in murine models. AB - BACKGROUND: Blockade of the renin-angiotensin system (RAS) has been shown to alleviate inflammatory processes in the gastrointestinal tract. The aim of this study was to determine if blockade of the RAS would be effective in an immunologically relevant colitis model, and to compare outcome with an acute colitis model. METHODS: A losartan analog, CCG-203025 (C23H26ClN3O5S) containing a highly polar sulfonic acid moiety that we expected would allow localized mucosal antagonism with minimal systemic absorption was selected as an angiotensin II type 1a receptor antagonist (AT1aR-A). Two colitis models were studied: (1) Acute colitis was induced in 8- to 10-week-old C57BL/6J mice by 2.5 % dextran sodium sulfate (DSS, in drinking water) for 7 days. (2) IL10-/-colitis Piroxicam (200 ppm) was administered orally in feed to 5-week-old IL-10-/-mice (C57BL/6J background) for 14 days followed by enalaprilat (ACE-I), CCG-203025 or PBS administered transanally for 14 days. RESULTS: In the DSS model, weight loss and histologic score for CCG-203025 were better than with placebo. In the IL10-/ model, ACE-I suppressed histologic damage better than CCG-203025. Both ACE-I and CCG-203025 reduced pro-inflammatory cytokines and chemokines. CONCLUSIONS: This study demonstrated the therapeutic efficacy of both ACE-I and AT1aR-A for preventing the development of both acute and immunologically relevant colitis. PMID- 27670280 TI - Assessing Spatial Relationships Between Rates of Crime and Rates of Gonorrhea and Chlamydia in Chicago, 2012. AB - Sexually transmitted infections (STIs) remain serious public health problems particularly in urban environments in the USA. Despite accumulating research into the role of aggregate rates of crime in shaping rates of STIs, few studies account for spatial dependence in the structure of geographical data. Using multiple spatial analysis methodologies, the following study investigated spatial patterns in community area rates of violent, drug, and property crimes and rates of infection of gonorrhea and chlamydia in 77 community areas in Chicago. Moran's I analyses confirmed global spatial dependence and statistically significant clusters of STI. Spatial lag regression analyses found that greater rates of drug crimes were associated with higher rates of chlamydia and gonorrhea after adjusting for percent in poverty and racial composition. Finally, a weighted geographic regression identified regions in the urban environment in which local regression coefficient values diverged from their global estimates. Spatial heterogeneity of STIs suggest that public health interventions must be targeted to specific areas of the urban environment with particular attention to substance use. PMID- 27670281 TI - Bone turnover markers and the factors associated with atypical femur fractures among Japanese patients. AB - Many previous reports have indicated that atypical femur fractures (AFFs) are associated with the administration of bisphosphonates (BPs). A number of risk factors and hypotheses regarding the pathogenesis of AFFs have been reported to date. The purpose of the present study was to identify the factors associated with AFFs in Japanese individuals and to elucidate the association between bone metabolism and AFFs by evaluating bone turnover markers (BTMs). We prospectively reviewed all patients with femur fractures and identified the patients with AFFs and typical femur fractures (TFFs). We collected the demographic and clinical data that were relevant to the present study, namely age, gender, affected side, affected site, concomitant medical history, and comorbid conditions, and measured the levels of BTMs within 24h after trauma. Welch's test and Fisher's exact probability test were used for the statistical analyses. A total of 338 patients, including 10 patients with AFFs and 328 patients with TFFs, were analyzed under the inclusion criteria. The use of BPs (p<0.001) and collagen disease and chronic granulomatous disease (CD/CGD) (p=0.025) were more frequently observed in patients with AFFs than in patients with TFFs, while the levels of BTMs, including N-terminal propeptides of type 1 procollagen (P1NP), isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) and undercarboxylated osteocalcin (ucOC) were significantly lower in patients with AFFs than in patients with TFFs. Furthermore, the level of TRACP-5b was found to be significantly lower in patients with atypical subtrochanteric fractures than in atypical diaphyseal fractures (p=0.025). Moreover, the levels of P1NP (p=0.016) and TRACP-5b (p=0.015) were found to be significantly lower in patients with AFFs than in patients with TFFs in a subgroup analysis of BPs users. The use of BPs was considered to be a factor associated with AFFs. Our comparison of the BTMs in patients with AFFs and TFFs indicated that the severe suppression of bone turnover was associated with the pathogenesis of AFFs. The extent of the influence of suppressed turnover on the pathogenesis of AFFs may differ depending on the fracture site. PMID- 27670283 TI - Place orientation and visual construction subdomains of the Mini Mental State Examination test as predictors of rehabilitation outcome of post-acute hip fractured patients. AB - PURPOSE: The study aimed at assessing the relationship between various Mini Mental State Examination (MMSE) subdomains and rehabilitation achievements in post-acute hip-fractured patients. METHOD: Six hundred and five hip-fractured patients admitted during 2010-2013 to a post-acute geriatric rehabilitation center were included in the study. Main outcome measures were the Functional Independence Measure (FIM) instrument, the motor FIM (mFIM), the Montebello Rehabilitation Factor Score (MRFS) on the mFIM and length of stay (LOS). A logistic regression analysis tested the predictive value of MMSE subdomains for achieving a satisfactory functional gain (mFIM MRFS >30%) on operated patients admitted from community. RESULTS: Of all the six MMSE subdomains, place orientation and visual construction demonstrated significant predictive values for rehabilitation outcome. Patients who did not err on place orientation and visual construction MMSE domains had better probabilities [(OR 1.28, 95%CI, 1.05 1.58; p = 0.017); (OR 2.15, 95%CI, 1.28-3.59; p = 0.004), respectively] of achieving better rehabilitation achievements. Similar results were obtained for cognitively impaired patient groups [(OR 1.40 95%CI, 1.11-1.77; p = 0.005); (OR 2.47, 95%CI, 1.15-5.30; p = 0.021), respectively]. For the cognitively intact patient group, the variables with significant predictive value were time orientation and visual construction MMSE subdomains [(OR 2.26, 95%CI, 1.18-4.33; p = 0.014); (OR 2.87, 95%CI, 1.16-7.09; p = 0.022), respectively]. CONCLUSIONS: Post-acute hip-fractured patients scoring normally on place orientation and visual construction MMSE subdomains have a better chance of achieving favorable rehabilitation outcome. Implications for Rehabilitation Post-acute hip-fractured patients have a better chance to achieve a favorable rehabilitation outcome when scoring normally on place orientation and visual construction MMSE subdomains. Patients having difficulties in orientation and visual construction may need more rehabilitation time as they lack planning and organizational capacity to follow instructions. Assessing MMSE subdomains may reveal subtle cognitive impairment in patients scored within the normal range on the MMSE test. Identifying subtle cognitive impairment may assist in coordinating the patients and their caregivers' expectations, efficiently allocating resources and help in advanced care planning. PMID- 27670282 TI - Quantitative characterization of in vitro bystander effect of antibody-drug conjugates. AB - Antibody-drug conjugates (ADCs) are designed to target antigen expressing (Ag+) cells in a tumor. Once processed by the Ag+ cells, ADCs can release cytotoxic drug molecules that can diffuse out of Ag+ cells into the neighboring antigen negative (Ag-) cells to induce their cytotoxicity. This additional efficacy of ADCs on Ag- cells in the presence of Ag+ cells is known as the 'bystander effect'. Although the importance of this phenomena is widely acknowledged for effective killing of a heterogeneous tumor, the rate and extent of the bystander killing in a heterogeneous system is not quantitatively understood yet. Thus, the objectives of this manuscript were to: (1) synthesize and characterize a tool ADC Trastuzumab-vc-MMAE that is capable of exhibiting bystander effect, (2) quantify the time course of the bystander effect for the tool ADC using in vitro co culture systems created using mixture of various HER2-expressing cell lines, and (3) develop a pharmacodynamic (PD) model that is capable of characterizing the bystander effect of ADCs. Co-culture studies conducted using GFP labelled MCF7 cells as Ag- cells and N87, BT474, and SKBR3 as Ag+ cells revealed that the bystander effect of ADC increases with increasing fraction of Ag+ cells in a co culture system, and with increased expression level of target on Ag+ cells. A notable lag time after ADC incubation was also observed prior to significant bystander killing of Ag- cells. Based on our results we hypothesize that there may be other determinants apart from the antigen expression level that can also influence the ability of Ag+ cells to demonstrate the bystander effect in a co culture system. The co-culture analysis also suggested that the bystander effect of the ADC can dissipate over the period of time as the population of Ag+ cells declines. A novel PD model was developed to mathematically characterize the bystander effect of ADCs by combining two different cell distribution models to represent the population of Ag+ and Ag- cells in a co-culture system. This PD model can be integrated with the systems PK model for ADCs in the future to generate a quantitative framework that is capable of supporting the discovery and development of novel ADCs with optimal bystander killing capabilities. PMID- 27670284 TI - Measuring and Facilitating Client Engagement with Financial Incentives: Implications for Improving Clinical Outcomes in a Mental Health Setting. AB - Significant numbers of individuals with severe mental illnesses are difficult to engage in treatment services, presenting challenges for care. To be able to assess the relationship between engagement and discharge outcomes, we modified the "Milestones of Recovery Scale". This scale was modified for content to match the current clinical setting, evaluated for inter-rater reliability after modification in a sample of 233 cases receiving psychiatric rehabilitation, and then was administered to 423 additional psychiatric rehabilitation clients over a 24-month study period. In an effort to determine whether provision of financial incentives lead to sustained increases in client engagement, a cut off for client eligibility for financial incentives was evaluated on the basis of the reliability study and the course of engagement was related to receipt of this incentive and successful completion of treatment in a new sample of 423 patients. Of this sample, 78 % received an initial financial incentive during treatment (were initially engaged), and 93.3 % of that subgroup sustained this level of engagement it over their entire course of treatment. Of the 22 % of cases not receiving an initial incentive, only 5.4 % improved in their engagement to levels required for the incentive. Longitudinal analysis demonstrated that individuals who maintained or increased their level of engagement over time were more likely to complete treatment in accordance with planned treatment goals. The initial engagement and the course of engagement in treatment predicted successful completion, but incentives did not lead to increased engagement in initially poorly engaged patients. These data are interpreted in terms of the likely success of extrinsic rewards to increase engagement in mental health services. PMID- 27670285 TI - Biochemical Characterization and Low-Resolution SAXS Molecular Envelope of GH1 beta-Glycosidase from Saccharophagus degradans. AB - The marine bacteria Saccharophagus degradans (also known as Microbulbifer degradans), are rod-shaped and gram-negative motile gamma-proteobacteria, capable of both degrading a variety of complex polysaccharides and fermenting monosaccharides into ethanol. In order to obtain insights into structure-function relationships of the enzymes, involved in these biochemical processes, we characterized a S. degradans beta-glycosidase from glycoside hydrolase family 1 (SdBgl1B). SdBgl1B has the optimum pH of 6.0 and a melting temperature T m of approximately 50 degrees C. The enzyme has high specificity toward short D glucose saccharides with beta-linkages with the following preferences beta-1,3 > beta-1,4 ? beta-1,6. The enzyme kinetic parameters, obtained using artificial substrates p-beta-NPGlu and p-beta-NPFuc and also the disaccharides cellobiose, gentiobiose and laminaribiose, revealed SdBgl1B preference for p-beta-NPGlu and laminaribiose, which indicates its affinity for glucose and also preference for beta-1,3 linkages. To better understand structural basis of the enzyme activity its 3D model was built and analysed. The 3D model fits well into the experimentally retrieved low-resolution SAXS-based envelope of the enzyme, confirming monomeric state of SdBgl1B in solution. PMID- 27670286 TI - Avian influenza A(H7N9) and (H5N1) infections among poultry and swine workers and the general population in Beijing, China, 2013-2015. AB - Although several studies have reported seroprevalences of antibody against avian influenza A(H7N9) virus among poultry workers in southern China, results have varied and data in northern China are scarce. To understand risks of H7N9 and H5N1 virus infections in northern China, a serological cohort study was conducted. Poultry workers, swine workers and the general population in Beijing, China, were evaluated through three surveys in November 2013, April 2014 and April 2015. The highest seroprevalence to H7N9 virus among poultry workers was recorded in the April 2014 and April 2015 surveys (0.4%), while that to H5N1 clade 2.3.4 or clade 2.3.2.1 virus was noted in the April 2014 survey (1.6% and 0.2%, respectively). The incidence of H7N9 virus infections among poultry workers (1.6/1000 person-months) was significantly lower than that of H5N1 clade 2.3.4 infections (3.8/1000 person-months) but higher than that of H5N1 clade 2.3.2.1 infections (0.3/1000 person-months). Compared with the general population, poultry workers were at higher risk of contracting H7N9 virus (IRR: 34.90; p < 0.001) or H5N1 clade 2.3.4 virus (IRR: 10.58; p < 0.001). Although risks of H7N9 and H5N1 virus infections remain low in Beijing, continued preventive measures are warranted for poultry workers. PMID- 27670287 TI - Incremental validity of the PID-5 in relation to the five factor model and traditional polythetic personality criteria of the DSM-5. AB - BACKGROUND: This study assessed the incremental validity of the Personality Inventory for DSM-5 (PID-5) beyond the impact of demographic, burden of illness, five-factor model of personality, and DSM-5 personality disorder criteria with respect to associations with admission psychiatric symptoms and functional disability. METHODS: Psychiatric inpatients (N = 927) were administered the Big Five Inventory, PID-5, and personality disorder criteria counts. Prior treatment utilization, as well as baseline depression, anxiety, emotion regulation, and functional disability were administered within two days of the personality measures. Hierarchical regression models were used to explore the association of personality functioning with symptom functioning, emotion regulation and disability. RESULTS: Neuroticism was associated with all symptom measures, providing further support for its relevance in clinical populations. Personality trait domains (negative affect, detachment, and psychoticism) from the PID-5 demonstrated incremental validity in predicting baseline symptom and disability functioning over and above demographic, burden of illness, and psychiatric comorbidity and five-factor model (FFM) personality traits. CONCLUSIONS: Dimensional measures of personality functioning were consistently associated with baseline symptom functioning, supporting the relevance of personality functioning as it relates to psychiatric symptoms. The PID-5 uniquely contributed to the prediction of baseline symptom functioning, thus providing incremental validity over gold-standard personality trait measures. PMID- 27670288 TI - The differential effects of emotional salience on direct associative and relational memory during a nap. AB - Relational memories are formed from shared components between directly learned memory associations, flexibly linking learned information to better inform future judgments. Sleep has been found to facilitate both direct associative and relational memories. However, the impact of incorporating emotionally salient information into learned material and the interaction of emotional salience and sleep in facilitating both types of memory is unknown. Participants encoded two sets of picture pairs, with either emotionally negative or neutral objects paired with neutral faces. The same objects were present in both sets, paired with two different faces across the sets. Baseline memory for these directly paired associates was tested immediately after encoding, followed by either a 90-min nap opportunity or wakefulness. Five hours after learning, a surprise test assessed relational memory, the indirect association between two faces paired with the same object during encoding, followed by a retest of direct associative memory. Overall, negative information was remembered better than neutral for directly learned pairs. A nap facilitated both preservation of direct associative memories and formation of relational memories, compared to remaining awake. Interestingly, however, this sleep benefit was observed specifically for neutral directly paired associates, while both neutral and negative relational associations benefitted from a nap. Finally, REM sleep played opposing roles in neutral direct and relational associative memory formation, with more REM sleep leading to forgetting of direct associations but promoting relational associations, suggesting that, while not benefitting memory consolidation for directly learned details, REM sleep may foster the memory reorganization needed for relational memory. PMID- 27670290 TI - Segmental Arterial Mediolysis. PMID- 27670289 TI - PLGA nanoparticles for intravitreal peptide delivery: statistical optimization, characterization and toxicity evaluation. AB - Frequent intravitreal injections are currently used to overcome the ocular barriers and provide sufficient drug to the posterior eye segment. However, intravitreal injections have been associated with a number of complications and high treatment costs. To overcome these limitations, peptide-loaded poly(d,l lactic-co-glycolic acid) nanoparticles (PLGA NPs) were developed using the nanoprecipitation technique and were optimized via Box-Behnken Design (BBD) and Response Surface Methodology (RSM). Developed NPs were evaluated for potential toxicity and cell apoptosis using the zebrafish embryo toxicity (ZET) model with titanium dioxide NPs and ethanol (1% v/v) serving as positive controls. Developed NPs had a size of 75.6-153.8 nm, a polydispersity index between 0.11 and 0.25 and a zeta potential of -9.4 to -46.0 mV. Loaded peptide was found to be stable under various experimental conditions tested. BBD and RSM were validated through the characterization of optimized formulations. Survival and hatching rates of NP treated zebrafish 0-144 h post-fertilization were found to be normal with no significant malformations. Cellular apoptosis studies also endorsed the non cytotoxic nature of the NPs. The overall results indicate that optimized PLGA nanoparticles could be a promising platform for efficient peptide delivery to the posterior segment of the eye. PMID- 27670291 TI - Stathmin-dependent molecular targeting therapy for malignant tumor: the latest 5 years' discoveries and developments. AB - Knowledge of the molecular mechanisms on malignant tumors is very critical for the development of new treatment strategies like molecularly targeted therapies. In last 5 years, many investigations suggest that stathmin is over-expressed in a variety of human malignant tumors, and potentially promotes the occurrence and development of tumors. Rather, down-regulation of stathmin can reduce cell proliferation, motility and metastasis and induce apoptosis of malignant tumors. Thus, a stathmin antagonist, such as a specific inhibitor (antibody, small molecule compound, peptide, or siRNA), may be a novel strategy of molecular targeted therapy. This review summarizes the research progress of recent 5 years on the role of stathmin in tumorigenesis, the molecular mechanisms and development of anti-stathmin treatment, which suggest that continued investigations into the function of stathmin in the tumorigenesis could lead to more rationally designed therapeutics targeting stathmin for treating human malignant tumors. PMID- 27670292 TI - Effect of fluoride varnish with added casein phosphopeptide-amorphous calcium phosphate on the acid resistance of the primary enamel. AB - BACKGROUND: This study aimed to investigate the effects of a fluoride varnish with added Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) treatments on acid resistance of primary teeth enamel. METHODS: Enamel specimens obtained from 40 primary incisors (for surface microhardness testing) and 40 primary molars (for demineralization depth measurement) were randomly divided into four groups (n = 10 incisors and 10 molars) each according to surface treatment: no treatment (control), MI varnish (1-8 % sodium fluoride and 1-5 % CPP-ACP), Clinpro White (1-5 % sodium fluoride and <5 % modified tricalcium phosphate), Duraphat (<5 % sodium fluoride). Specimens were stored for 24 h in a moist environment. After varnish residues were removed, specimens were subjected to pH cycling. The effects of fluoride varnishes were evaluated according to surface microhardness, lesion depth and structural changes. Results were analyzed by ANOVA and Tukey's tests. RESULTS: The lowest changes in surface microhardness and lesion depth occurred in MI varnish group, followed by the Clinpro White, Duraphat and no treatment (control) group (for percentage of loss surface microhardness -20.80, -34.60, -57.80 and -73.40; for lesion depth values 23.60 MUm +/- 3.36, 29.85 MUm +/- 3.27, 40.37 MUm +/- 3.41 and 54.56 MUm +/- 4.16, respectively). Statistically significant differences in both surface microhardness and lesion depth were observed among all groups (P < 0.05). CONCLUSIONS: Within the limitations of this in vitro study, fluoride varnish containing CPP-ACP was more effective in increasing the acid resistance of primary enamel than other fluoride varnishes. However, further clinical research is needed to confirm these in vitro results. PMID- 27670293 TI - Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa. AB - Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive degeneration of the retinal photoreceptor cells. This study aims to identify genetic mutations in a Chinese family RP-2236, an Indian family RP-IC 90 and 100 sporadic Indian individuals with autosomal recessive RP (arRP). Whole exome sequencing was performed on the index patients of RP-2236, RP-IC-90 and all of the 100 sporadic Indian patients. Direct Sanger sequencing was used to validate the mutations identified. Four novel mutations and one reported mutation in the crumbs homolog 1 (CRB1) gene, which has been known to cause severe retinal dystrophies, were identified. A novel homozygous splicing mutation c.2129-1G>C was found in the three patients In family RP-2236. A homozygous point mutation p.R664C was found in RP-IC-90. A novel homozygous mutation p.G1310C was identified in patient I-44, while novel compound heterozygous mutations p.N629D and p.A593T were found in patient I-7. All mutations described above were not present in the 1000 normal controls. In conclusion, we identified four novel mutations in CRB1 in a cohort of RP patients from the Chinese and Indian populations. Our data enlarges the CRB1 mutation spectrums and may provide new target loci for RP diagnose and treatment. PMID- 27670294 TI - The implications of living with heart failure; the impact on everyday life, family support, co-morbidities and access to healthcare: a secondary qualitative analysis. AB - BACKGROUND: The aim of this study was to use secondary analysis to interrogate a qualitative data set to explore the experiences of patients living with heart failure. METHODS: The data-set comprised interviews with 11 patients who had participated in an ethnographic study of heart failure focusing on unplanned hospital admissions. Following an initial review of the literature, a framework was developed with which to interrogate the data-set. This was modified in light of analysis of the first two interviews, to focus on the rich data around patients' perceptions of living with heart failure, managing co-morbidities, accessing healthcare and the role of their family and friends, during their illness journey. RESULTS: Respondents described how the symptoms of heart failure impacted on their daily lives and how disruption of routine activity due to their symptoms caused them to seek medical care. Respondents disclosed the difficulties of living with other illnesses, in addition to their heart failure, particularly managing multiple and complex medication regimes and negotiating multiple appointments; all expressed a desire to return to their pre-morbid, more independent lives. Many respondents described uncertainty around diagnosis and delays in communication from their healthcare providers. The importance of family support was emphasised, but respondents worried about burdening relatives with their illness. CONCLUSION: Living with heart failure causes disruption to the lives of sufferers. Facilitation of access to healthcare, through good communication between services and having a strong support network of both family and clinicians can reduce the impact of heart failure on the lives of the patient and those around them. PMID- 27670301 TI - The challenge of cancer: improving essential nursing skills. AB - The aim of this Learning Unit is to identify the role of the registered nurse in facilitating the learning process and in supporting the student caring for people with cancer, by highlighting the necessary skills and demonstrating ways in which he or she can pass on his or her experience. PMID- 27670302 TI - Editorial. AB - Media coverage of the emotive issue of nurses' pay had the ministerial and management hardliners pontificating on the worth of nurses last week. Not worth enough however to warrant a decent pay increase. Kind words and sympathetic platitudes are in endless supply, it's just hard cash. PMID- 27670300 TI - Comparison of quartz vials with polypropylene vials for rapid cryopreservation of human ovarian tissue. AB - BACKGROUND: Because higher survival of follicles during the freezing/thawing procedure improves the quality of cryopreserved tissue reimplanted after oncological therapies, defining an optimal method for human ovarian tissue cryopreservation remains a major issue in this field. One option to improve the cryopreservation procedure is to use better materials, i.e., vials with better conductivity. The aim of this study was to compare polypropylene (PP) with quartz vials. Between September 2012 and January 2013, eight patients were recruited. The ovarian cortex was cut into 3 slices, assigned randomly to a fresh and a cryopreserved group in PP (method B) or quartz vials (method C). Histological and immunohistochemical (IHC) analysis were used. For IHC three antibodies were analyzed: Ki67 (proliferation index), Bcl2 (anti apoptotic index) and Hsp70 (stress index). RESULTS: The majority of GCs showed positive staining for Bcl2 in both cryopreservation device, with higher expression in group C than in group B. Oocytes and their nuclei showed intense positive staining for ki67 in both methods B and C, and also a patch positive stromal cells staining for Ki67. Expression of hsp70 was not increased after cryopreservation. CONCLUSIONS: Cryopreservation using quartz vials led to larger numbers of good follicles while maintaining consistent preservation for stromal cells and vessels. PMID- 27670299 TI - Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions. AB - It is well known that interferons (IFNs), such as type-I IFN (IFN-alpha) and type II IFN (IFN-gamma) are produced by immune cells to elicit antiviral effects. IFNs are also produced by glial cells in the CNS to regulate brain functions. As a proinflammatory cytokine, IFN-gamma drives neuropathic pain by inducing microglial activation in the spinal cord. However, little is known about the role of IFN-alpha in regulating pain sensitivity and synaptic transmission. Strikingly, we found that IFN-alpha/beta receptor (type-I IFN receptor) was expressed by primary afferent terminals in the superficial dorsal horn that co expressed the neuropeptide CGRP. In the spinal cord IFN-alpha was primarily expressed by astrocytes. Perfusion of spinal cord slices with IFN-alpha suppressed excitatory synaptic transmission by reducing the frequency of spontaneous excitatory postsynaptic current (sEPSCs). IFN-alpha also inhibited nociceptive transmission by reducing capsaicin-induced internalization of NK-1 and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial dorsal horn neurons. Finally, spinal (intrathecal) administration of IFN-alpha reduced inflammatory pain and increased pain threshold in naive rats, whereas removal of endogenous IFN-alpha by a neutralizing antibody induced hyperalgesia. Our findings suggest a new form of neuronal-glial interaction by which IFN-alpha, produced by astrocytes, inhibits nociceptive transmission in the spinal cord. PMID- 27670303 TI - Four in five nurses against performance-related pay proposal, claims Unison. AB - Fury at the government's bid to introduce performance-related pay to nursing has continued to grow over the past year with four in five nurses opposed to the plans, Unison claims in its evidence. PMID- 27670304 TI - Rise in NHS productivity is due to nurses' unpaid overtime. AB - The government's boasted increase in the number of patients treated by the NHS is at the expense of nurses' unpaid overtime, it was revealed this week. PMID- 27670305 TI - Unions call for 8.34% pay increase. AB - The nurses' pay Review Body should reject government calls for a zero national pay increase and award a 'fair and just' rise, Staff Side urged last week. PMID- 27670307 TI - Extended use of bank nurses recommended. AB - The use of nursing banks should be extended to include areas other than traditional nursing where staff are needed on short notice, a report for the Scottish Office has recommended. PMID- 27670306 TI - ? AB - Tender touch: Incubated premature babies at Whipps Cross Hospital in east London have been receiving massage from Gill Tree, director of the local Essentials for Health School of Massage. Her work has generated so much interest that she is organising a series of one-day training workshops to teach nurses the technique and its application in special care. She claims 90 per cent of babies respond well, becoming more relaxed and happy. PMID- 27670308 TI - Monday launch for nurse prescribing. AB - District nurses and health visitors at eight selected fundholding practices will be able to prescribe from a limited formulary of drugs and products from Monday morning. PMID- 27670309 TI - Drastic loss of nursing jobs in London. AB - News that the number of nurses working in London has dropped by almost 11 per cent over the past year has been greeted with alarm by nursing unions. PMID- 27670310 TI - 'Poor' mental health care in prisons. AB - Poor co-operation between the NHS and the prison service is leaving prisoners with serious mental illness poorly cared for, a King's Fund report has alleged. PMID- 27670312 TI - Video aimed at nurses in measles campaign. AB - School nurses involved in the government's measles immunisation campaign have been urged to watch a special edition of the RCN's Nursing Update learning unit devoted to the campaign which will go out next month. PMID- 27670311 TI - New charity for bereaved families. AB - A new charity to improve professional support to families who have lost a child was launched in London this week. PMID- 27670313 TI - Nurses support sacked consultant who spoke out on trusts. AB - Nurses have rallied to the support of a hospital consultant who was sacked after leading an outcry against the hospital becoming an NHS trust. PMID- 27670314 TI - DoH accused of under funding school study. AB - The Department of Health has been criticised for under funding a highly successful pilot study on the use of service agreements for school nurses. PMID- 27670316 TI - ? AB - Changing face: Giant metal sculptures from the Yorkshire Sculpture Park have been put on show in the grounds of Ashworth Hospital in Merseyside. The nine-month exhibition is titled 'Facing the wall'. PMID- 27670317 TI - RCN wins Lib-Dem prize for best exhibition. AB - Liberal Democrat leader Paddy Ashdown handed over a magnum of champagne to the Royal College of Nursing after the College won first prize for the best exhibition at the Brighton conference. PMID- 27670318 TI - ? AB - Past and present: Photographer Maria Pedro's self-portrait as the pioneering 19th Century nurse Mary Seacole is currently on show at 76 Marylebone High Street, London until October 8, as part of the Signals Festival of Women Photographers which will cover up to 200 venues across the United Kingdom. PMID- 27670319 TI - UKCC ballot to choose mediators. AB - A ballot of UK Central Council members will determine who sits on the Council committee being set up in an attempt to mediate between Registrar Colin Ralph and disaffected senior staff. PMID- 27670320 TI - Nurses ill-prepared for new-look NHS. AB - Royal College of Nursing (RCN) General Secretary Christine Hancock believes a new agenda is now clearly emerging for the NHS but that nurses are inadequately prepared for the changes ahead. As a result nurses face an intolerable climate of insecurity, confronted by increased workloads and increasing administration. Her grim vision of the future was revealed as Miss Hancock began her annual tour of the party conferences at the Liberal Democrats conference. PMID- 27670321 TI - Sacked nurse holds ground against trust. AB - The stalemate between sacked nurse Pat Cooksley and Plymouth Hospitals Trust continued last week with both sides refusing to meet until the other had removed 'preconditions'. PMID- 27670322 TI - ? AB - Binding memory: Veteran paratroopers who survived the Arnhem landing in September 1944, honoured Dutch nurse Kate Ter Horst when they marked the 50th anniversary of the event. Kate nursed hundreds of the badly-wounded and dying during the raid and provided a haven for 300 British casualties at her home . A copy of her book Cloud over Arnhem was presented to the Lancashire College of Nursing and Health Studies by the Central Lancashire Branch of the Parachute Regimental Association. At the ceremony, third-year nursing student Catherine Kelly (pictured) read the same psalm which Kate Ter Horst read at the height of the battle. The original scene was portrayed in the film A Bridge Too Far. PMID- 27670323 TI - Hospitals relaxing infection controls. AB - Hospital acquired infection rates could reach epidemic proportions if managers do not maintain screening systems, the RCN warned last week. PMID- 27670324 TI - Government cot death campaign had only 'limited impact'. AB - The government's campaign to reduce the number of cot deaths has had only a limited impact. Despite the number of cot deaths being halved in the first year of the health department's 'Back to Sleep' initiative, there is little evidence child care practice has changed, researchers from Cambridge University argue. The campaign, launched in December 1991, advised parents that babies should not sleep on their front, be exposed to cigarette smoke or be overheated. The researchers say the campaign has had no influence on parents' smoking habits or on the prevalence of breast feeding. Royal College of Nursing midwifery' adviser Vicki Nix said nurses should continue to put across key health promotion messages forcefully to ensure the momentum of the campaign was not lost. Encouraging breast feeding and advising the baby's family to stop smoking should particularly be promoted, she said. PMID- 27670325 TI - Nurses vital in fight against obesity. AB - The Department of Health (DoH) nutrition task force will soon publish a document to identify the key nutritional components of health professional education and training and give advice on how to communicate nutritional messages, chief nursing officer Yvonne Moores said last week. PMID- 27670326 TI - RCN concerned over low life expectancy figures for Scottish women. AB - News that Scotland's women have the lowest life expectancy in western Europe has been deplored by the Royal College of Nursing. PMID- 27670328 TI - Campaign launched to support 'isolated' nurses. AB - A new campaign which aims to offer support to nurses who feel isolated and unable to express concerns about standards of care has been launched with the backing of sacked charge nurse Graham Pink. PMID- 27670327 TI - Pritchard off to Brussels. AB - Phylip Pritchard is leaving his post as European Officer at the RCN to head up the Brussels office of the Federation of European Cancer Nursing Societies from the beginning of February 1995. PMID- 27670330 TI - Routine data can help evaluate discharge planning. AB - Routinely available data does not make if possible to determine which readmissions are avoidable but could be better used to identify high risk patients, the first independent study into trauma and orthopaedics has shown. PMID- 27670329 TI - Kent school nurses help reduce under-age sex by 50. AB - School nurses in south-east Kent Community Healthcare Trust have made 'staggering' progress to reduce unwanted teenage pregnancies and meet the Health of the Nation target to reduce under-age sex by 50 per cent, the conference heard last week. PMID- 27670331 TI - Relaxation techniques can ease pain. AB - People with chronic non- malignant pain could manage their pain better if they were taught relaxation, according to researchers in Oxford. PMID- 27670332 TI - RCN orthopaedic nursing conference. AB - The RCN Society of Orthopaedic Nursing international conference was staged at a hospital for the first time. Nurses attended workshops at the Royal National Orthopaedic Hospital Trust in Stanmore, including new techniques for treating primary bone cancer. Thelma, aged three, is wearing a halo jacket to correct a defect in the curvature of her spine. She is pictured here with nurse Marie Gallagher. PMID- 27670333 TI - 'Move into health' call. AB - Orthopaedic nurses should move into health and away from disease, developing their specialist skills to 'predict and prevent not diagnose and treat' conditions affecting the locomotor system, the conference heard. PMID- 27670334 TI - Maternal transmission of HSV underestimated? AB - The frequency of infant exposure to secretions containing herpes simplex virus (HSV) from seropositive women might be eight times higher than previously estimated and might be associated with an increased frequency of transmission. PMID- 27670335 TI - Potency of hypoxia in near-death experiences. AB - 'Near death experiences' might represent an agonal limbic syndrome rather than a glimpse into the afterlife, according to German researchers. While the existence of such experiences is no longer debatable, their origin is still a matter of controversy. Physiological, psychological and transcendental explanations have all been suggested. PMID- 27670336 TI - Fibromyalgia and psychological symptoms. AB - Fibromyalgia, as characterised by widespread persistent musculoskeletal pain, does not seem to be a distinct disease entity, researchers from Manchester say. PMID- 27670338 TI - No sympathy for men's problems. AB - Having read Verity Pink's recent article (Smear campaign, Viewpoint, August 31), I was pleased to see that she wondered how well health care workers understood male celibacy. This prompted me to write, to relate my recent experiences. PMID- 27670337 TI - Prolonging the life of dialysis catheters. AB - Urokinase is safe and effective in restoring patency to clotted, double lumen catheters used for renal dialysis, according to an American nurse researcher. PMID- 27670339 TI - Sister Cooksley's action 'dangerous' to patients. AB - The recent publicity focusing on Sister Cooksley has widened the debate about the evolving role of nurses in relation to the prescribing and administration of drugs. This may well lead to future changes to the law, local rules and professional guidelines issued to nurses. PMID- 27670340 TI - Weekly cardiology update, please. AB - In response to your request in Nursing Standard (August 31), I have put pen to paper in order to say that I find Cardiology Update extremely interesting, educational and useful in my work on an acute medical ward. The articles often help me to understand procedures and theories which in turn enhances my patient care. PMID- 27670341 TI - Continuing care not community care. AB - Well, they've done it again. On a Friday afternoon in August, the latest stab in the back for the beleagured NHS was announced, new 'guidelines' for the continued provision of continuing care by the NHS. PMID- 27670343 TI - Information exchange. AB - * As a clinical nurse specialist in HIV/AIDS, I am looking at forming a respite unit which, of necessity, has to be accommodated within the acute services setting. Has anyone any experience of this? Did the difference in ethos prove a problem? Does it work? I would appreciate any comments from anyone, in any field, with experience of this. PMID- 27670342 TI - Unfair grants penalise graduates. AB - I entered nursing with a degree in economics so I was especially interested in your editor's comments on graduate recruitment on GMTV this morning (September 14). However, a unique and serious problems for graduate nurses is beginning co emerge. PMID- 27670344 TI - Glittering prizes. PMID- 27670345 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone became of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27670346 TI - Synthetic and Natural Nutritional Supplements: Health "Allies" or Risks to Public Health? AB - BACKGROUND: The modern way of life involves high stress levels, poor eating habits, lack of exercise, obesity and other detrimental health factors. Nutritional supplements (NS) are complexes of nutrients with variant activity that may infer reversal to nutrient depletion. They tend to be popular amongst social categories associated with the healthy life style, such as the elite and amateur athletes, military people and the general population. OBJECTIVE: An overview of the state of play with regard to nutritional supplements - natural and synthetic-, is important both from toxicological and commercial point of view. METHOD: From a thorough literature review on nutritional supplements, several patents of application have been identified and herewith reviewed which recommend natural vegetable extracts as food supplements for prophylaxis, therapy, protection of immune system, diabetes, oxidative stress, cancer, chronic inflammations and other health conditions. Besides, nutritional supplements of pharmacological validity and high popularity are discussed relative to their contents and group of use. RESULTS: Cases of adulteration or unintentional contamination of commercial products with abusing substances (doping substances, narcotics etc.) or toxic compounds (heavy metals, plant toxics) have shed light to the problem of causing recalls of some products by the FDA. CONCLUSION: From the safety/ quality point of view, NS lack of harmonisation and sovereign laws/ institutional controls on the market and their wide commercialization may possibly lead to risks to public health. PMID- 27670347 TI - Twister ribozymes as highly versatile expression platforms for artificial riboswitches. AB - The utilization of ribozyme-based synthetic switches in biotechnology has many advantages such as an increased robustness due to in cis regulation, small coding space and a high degree of modularity. The report of small endonucleolytic twister ribozymes provides new opportunities for the development of advanced tools for engineering synthetic genetic switches. Here we show that the twister ribozyme is distinguished as an outstandingly flexible expression platform, which in conjugation with three different aptamer domains, enables the construction of many different one- and two-input regulators of gene expression in both bacteria and yeast. Besides important implications in biotechnology and synthetic biology, the observed versatility in artificial genetic control set-ups hints at possible natural roles of this widespread ribozyme class. PMID- 27670348 TI - Association of corrected QT interval with body mass index, and the impact of this association on mortality: Results from the Third National Health and Nutrition Examination Survey. AB - BACKGROUND: Both QT interval and body mass index (BMI) are independently associated with mortality. Those with higher BMI have longer QT, although evidence is inconsistent. The joint association of QT and BMI with mortality merits investigation. OBJECTIVE: To examine the association of QT with BMI, and to examine the joint association of QT and BMI with all-cause and cardiovascular mortality. METHODS: We followed 4036 participants from NHANES III for a median of 14.7 years. Weighted sample was divided into 4 categories by BMI as: 18.5-24.9, 25-29.9, 30-34.9 and >=35, and 2 categories by corrected QT interval (QTc) as: normal (<450ms in males, <460ms in females) or prolonged. Cox proportional hazards models were used with adjustment for demographic characteristics and cardiovascular risk factors. RESULTS: QTc was longer among those with higher BMI (mean QTc: 424.7, 425.8, 430.9 and 437.8 respectively for BMI 18.5-24.9, 25-29.9, 30-34.9 and >=35, p-trend: <0.001). Overall, longer QTc or higher BMI were associated with increased all-cause and cardiovascular mortality risk compared to mean QTc or mean BMI, respectively. When combined, cardiovascular mortality was significantly increased among obese individuals with prolonged QTc [hazard ratio (95% CI): 3.1 (1.2-8.0) and 4.8 (1.2-19.9) but not when QTc was normal [1.0 (0.5 2.0) and 1.4 (0.8-2.8)] for BMI 30-34.9 and >=35, respectively compared to BMI 18.5-24.9 and normal QTc. Similar (although not statistically significant) findings were observed for all-cause mortality. Risk prediction for both all cause and cardiovascular mortality improved when QTc was added to the adjusted model with BMI (net reclassification index 0.14, p=0.01 and 0.14, p<0.0001 for all-cause and cardiovascular mortality, respectively). CONCLUSION: Individuals with higher BMI have a significantly longer QTc. BMI is associated with increased all-cause and cardiovascular mortality risk when QTc is prolonged but not when QTc is normal. These novel observations suggest that QTc should be factored into risk stratification of obese individuals with a screening electrocardiogram. This may help stratify individuals into lower risk categories when QTc is normal. PMID- 27670349 TI - The effect of high intensity statin use on liver density: A post hoc analysis of the coronary artery calcification treatment with zocor [CATZ] study. PMID- 27670350 TI - Overweight and obesity among Major League Baseball players: 1871-2015. AB - Professional athletes provide high-profile role models of health and human performance. Increased body mass can be adaptive for human performance but also presents a health threat. This paper examines 145 years of data on body mass in 17,918 male professional baseball players in the United States at the time of their professional debut. Both height and weight at debut have increased over time. Controlling for age at debut, players debuting in the current decade were significantly more likely to be overweight or obese than at any time in history. The prevalence of overweight and obesity increased to approximately 70% and 10%, respectively, while normal weight prevalence decreased from approximately 60% to 20% during that time. The causes of these changes over the past 25 years are not clear although they coincide with the steroid era. These trends warrant further attention because of the potential for adverse long-term health consequences in this population and those who perceive them as role models for health and human performance. PMID- 27670351 TI - Don't Save My Life: Do-Not-Resuscitate and End-of-Life Directives in the Context of EMS and Disaster Medicine. PMID- 27670352 TI - A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes. AB - Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin. PMID- 27670353 TI - Combined DOG1 and Mammaglobin Immunohistochemistry Is Comparable to ETV6 breakapart Analysis for Differentiating Between Papillary Cystic Variants of Acinic Cell Carcinoma and Mammary Analogue Secretory Carcinoma. AB - BACKGROUND: We investigated the reliability of combined DOG1 and mammaglobin immunohistochemistry compared with ETV6 fluorescence in situ hybridization (FISH) in the assessment of salivary tumors previously diagnosed as acinic cell carcinoma (ACC). Ultrastructural features of cases reclassified as mammary analogue secretory carcinoma (MASC) were assessed by transmission electron microscopy (TEM). METHODS: Immunohistochemical (IHC) reactivity to DOG1 and mammaglobin was validated against FISH targeting the ETV6 gene in all 14 cases. RESULTS: Three cases with papillary cystic histomorphology previously diagnosed as ACC were revised to MASC. TEM features of the ETV6 rearrangement-positive MASC cases showed large numbers of secretory granules with extrusion into the intercellular spaces, well-developed endoplasmic reticulum, lipid-laden vacuoles, well-formed microvilli, and large lining cystic spaces. CONCLUSIONS: Combined DOG1 and mammaglobin immunohistochemistry is comparable to ETV6 -breakapart analysis for differentiating between papillary cystic variants of ACC and MASC. PMID- 27670354 TI - Pseudomelanosis Duodeni. PMID- 27670355 TI - Highly Reproducible Ag NPs/CNT-Intercalated GO Membranes for Enrichment and SERS Detection of Antibiotics. AB - The increasing pollution of aquatic environments by antibiotics makes it necessary to develop efficient enrichment and sensitive detection methods for environmental antibiotics monitoring. In this work, silver nanoparticles and carbon nanotube-intercalated graphene oxide laminar membranes (Ag NPs/CNT-GO membranes) were successfully prepared for enrichment and surface-enhanced Raman scattering (SERS) detection of antibiotics. The prepared Ag NPs/CNT-GO membranes exhibited a high enrichment ability because of the pi-pi stacking and electrostatic interactions of GO toward antibiotic molecules, which enhanced the sensitivity of SERS measurements and enabled the antibiotics to be determined at sub-nM concentrations. In addition, the nanochannels created by the intercalation of CNTs into GO layers resulted in an 8-fold enhancement in the water permeance of Ag NPs/CNT-GO membranes compared to that of pure GO membranes. More importantly, the Ag NPs/CNT-GO membranes exhibited high reproducibility and long term stability. The spot-to-spot variation in SERS intensity was less than 15%, and the SERS performance was maintained for at least 70 days. The Ag NPs/CNT-GO membranes were also used for SERS detection of antibiotics in real samples; the results showed that the characteristic peaks of antibiotics were obviously recognizable. Thus, the sensitive SERS detection of antibiotics based on Ag NPs/CNT-GO offers great potential for practical applications in environmental analysis. PMID- 27670356 TI - Humeral elevation reduces the dynamic control ratio of the shoulder muscles during internal rotation. AB - OBJECTIVES: To determine the differences in the dynamic control ratio of the glenohumeral joint rotators, during internal rotation at 20 degrees and 60 degrees of humeral elevation in the scapular plan. Dynamic control ratio (DCR) is defined as the ratio between eccentric action of the lateral rotators and the concentric action of the medial rotators. DESIGN: A cross-sectional laboratory study. METHODS: Thirty asymptomatic participants (men n=14, women n=16, mean age=29.4+/-8.9years, BMI: 24.1+/-5.4) were tested. Peak torque generated by the concentric action of the MR and the eccentric action of the LR of the shoulder joint and the DCR were evaluated on the dominant arm using an isokinetic dynamometer at 20 degrees and 60 degrees of humeral elevation at a speed of 20 degrees /s. RESULTS: There was a significant decrease in the DCR at 60 degrees humeral elevation when compared to 20 degrees humeral elevation (p<0.05). This decrease was due to the significant decrease in eccentric peak torques at 60 degrees humeral elevation when compared to 20 degrees (p<0.05). However, there was no significant difference in the concentric peak torques between 20 degrees and 60 degrees (p>0.05). CONCLUSIONS: The significant decrease in the DCR as a consequence of a decrease in the eccentric peak torque of the LR when the humerus is in a more elevated position suggests that the introduction of humeral elevation can be used as a progression for improving the eccentric action of the shoulder LR and subsequently the dynamic control of the shoulder. PMID- 27670357 TI - Feasibility of the capnogram to monitor ventilation rate during cardiopulmonary resuscitation. AB - AIM: The rates of chest compressions (CCs) and ventilations are both important metrics to monitor the quality of cardiopulmonary resuscitation (CPR). Capnography permits monitoring ventilation, but the CCs provided during CPR corrupt the capnogram and compromise the accuracy of automatic ventilation detectors. The aim of this study was to evaluate the feasibility of an automatic algorithm based on the capnogram to detect ventilations and provide feedback on ventilation rate during CPR, specifically addressing intervals where CCs are delivered. METHODS: The dataset used to develop and test the algorithm contained in-hospital and out-of-hospital cardiac arrest episodes. The method relies on adaptive thresholding to detect ventilations in the first derivative of the capnogram. The performance of the detector was reported in terms of sensitivity (SE) and Positive Predictive Value (PPV). The overall performance was reported in terms of the rate error and errors in the hyperventilation alarms. Results were given separately for the intervals with CCs. RESULTS: A total of 83 episodes were considered, resulting in 4880min and 46,740 ventilations (8741 during CCs). The method showed an overall SE/PPV above 99% and 97% respectively, even in intervals with CCs. The error for the ventilation rate was below 1.8min-1 in any group, and >99% of the ventilation alarms were correctly detected. CONCLUSION: A method to provide accurate feedback on ventilation rate using only the capnogram is proposed. Its accuracy was proven even in intervals where canpography signal was severely corrupted by CCs. This algorithm could be integrated into monitor/defibrillators to provide reliable feedback on ventilation rate during CPR. PMID- 27670358 TI - Optimization of automated external defibrillator deployment outdoors: An evidence based approach. AB - BACKGROUND: The benefits of available automatic external defibrillators (AEDs) for out-of-hospital cardiac arrests (OHCAs) are well known, but strategies for their deployment outdoors remain somewhat arbitrary. Our study sought to assess different strategies for AED deployment. METHODS: All OHCAs in Paris between 2000 and 2010 were prospectively recorded and geocoded. A guidelines-based strategy of placing an AED in locations where more than one OHCA had occurred within the past five years was compared to two novel strategies: a grid-based strategy with a regular distance between AEDs and a landmark-based strategy. The expected number of AEDs necessary and their median (IQR) distance to the nearest OHCA were assessed for each strategy. RESULTS: Of 4176 OHCAs, 1372 (33%) occurred in public settings. The first strategy would result in the placement of 170 AEDs, with a distance to OHCA of 416 (180-614) m and a continuous increase in the number of AEDS. In the second strategy, the number of AEDs and their distance to the closest OHCA would change with the grid size, with a number of AEDs between 200 and 400 seeming optimal. In the third strategy, median distances between OHCAs and AEDs would be 324m if placed at post offices (n=195), 239 at subway stations (n=302), 137 at bike-sharing stations (n=957), and 142 at pharmacies (n=1466). CONCLUSION: This study presents an original evidence-based approach to strategies of AED deployment to optimize their number and location. This rational approach can estimate the optimal number of AEDs for any city. PMID- 27670359 TI - Low oxygen saturation and severe anemia in compound heterozygous Hb Louisville [beta42(CD1)Phe->Leu] and Hb La Desirade [beta129(H7)Ala->Val]. AB - OBJECTIVE: To investigate the cause(s) of a Thai male proband presenting low oxygen saturation by pulse oximetry (SpO2) and severe anemia. METHODS: As Hb variant was suspected, Hb typing was determined by high-performance liquid chromatography and capillary electrophoresis, and subsequently Hb variant was identified by DNA sequencing. Complete blood counts were performed using automated blood cell counter and oxygen saturation was measured by pulse oximetry. RESULTS: Proband was compound heterozygous for Hb Louisville [beta42(CD1)Phe->Leu] and Hb La Desirade [beta129(H7)Ala->Val]. Of the proband's two sons, one was compound heterozygous for Hb Louisville and Hb E and the other for Hb La Desirade and Hb E. The former son had similar clinical features and laboratory findings with those of the proband while the latter showed had no abnormal clinical manifestations. CONCLUSION: This the first report of compound heterozygosity of Hb Louisville and Hb La Desirade in an individual of Southeast Asian ethnicity. Hb variant identification is crucial for genetic counseling and appropriate treatment in regions where hemoglobinopathies are common. PMID- 27670361 TI - High Molecular Weight Hyaluronic Acid Inhibits Fibrosis of Endometrium. AB - BACKGROUND Elevated fibrosis has been found in patients with intrauterine adhesion, which indicates that fibrotic factors may play a critical role in formation of intrauterine adhesion. The aim of this study was to identify the effect of hyaluronic acid (HA) at high and low molecular weight on fibrosis of the endometrium in a mouse model of Asherman's syndrome. MATERIAL AND METHODS Endometrial fibrosis in a mouse model of Asherman's syndrome was confirmed. Then HA at high and low molecular weight was injected into the uterine cavity. Endometrial fibrosis was compared among the control group, LMW-HA, and HMW-HA group. The extent of endometrial fibrosis was calculated using Masson stain. The fibrosis markers (TGFbeta1, CTGF, collagen I, and collagen III) in endometrial tissue were detected using immunohistochemistry and Western blotting. RESULTS The ratio of the area with endometrial fibrosis to total endometrial area in the HMW HA group was significantly decreased compared to the control group (P<0.05). The expression of fibrosis markers (TGFbeta1, CTGF, collagen I, and collagen III) in the endometrium was attenuated in the HMW-HA group compared to the control group, but the LMW-HA group had no similar effect. CONCLUSIONS Hyaluronic acid at high molecular weight may attenuate the degree of endometrial fibrosis after endometrial damage, which may contribute to preventing formation of intrauterine adhesions. PMID- 27670363 TI - In-Depth Magnetic Characterization of a [2 * 2] Mn(III) Square Grid Using SQUID Magnetometry, Inelastic Neutron Scattering, and High-Field Electron Paramagnetic Resonance Spectroscopy. AB - A tetranuclear [2 * 2] grid-like manganese(III) Schiff base complex, Mn4, has been synthesized and characterized by single-crystal X-ray crystallography. Direct-current magnetization measurements were performed on the system and proved to be insufficient for an accurate magnetic model to be deduced. Combined inelastic neutron scattering (INS) and electron paramagnetic resonance (EPR) experiments provided the necessary information in order to successfully model the magnetic properties of Mn4. The resulting model takes into account both the magnitude and the relative orientations of the single-ion anisotropy tensors. PMID- 27670360 TI - The Inclusion of Ethnic Minority Patients and the Role of Language in Telehealth Trials for Type 2 Diabetes: A Systematic Review. AB - BACKGROUND: Type 2 diabetes is a serious, pervasive metabolic condition that disproportionately affects ethnic minority patients. Telehealth interventions can facilitate type 2 diabetes monitoring and prevent secondary complications. However, trials designed to test the effectiveness of telehealth interventions may underrecruit or exclude ethnic minority patients, with language a potential barrier to recruitment. The underrepresentation of minorities in trials limits the external validity of the findings for this key patient demographic. OBJECTIVE: This systematic review examines (1) the research reporting practices and prevalence of ethnic minority patients included in telehealth randomized controlled trials (RCTs) targeting type 2 diabetes and the trial characteristics associated with recruiting a high proportion of minority patients, and (2) the proportion of included RCTs that report using English language proficiency as a patient screening criterion and how and why they do so. METHODS: Telehealth RCTs published in refereed journals targeting type 2 diabetes as a primary condition for adults in Western majority English-speaking countries were included. Ethnically targeted RCTs were excluded from the main review, but were included in a post hoc subgroup analysis. Abstract and full-text screening, risk of bias assessment, and data extraction were independently conducted by two reviewers. RESULTS: Of 3358 records identified in the search, 79 articles comprising 58 RCTs were included. Nearly two-thirds of the RCTs (38/58) reported on the ethnic composition of participants, with a median proportion of 23.5% patients (range 0% 97.7%). Fourteen studies (24%) that included at least 30% minority patients were all US-based, predominantly recruited from urban areas, and described the target population as underserved, financially deprived, or uninsured. Eight of these 14 studies (57%) offered intervention materials in a language other than English or employed bilingual staff. Half of all identified RCTs (29/58) included language proficiency as a participant-screening criterion. Language proficiency was operationalized using nonstandardized measures (eg, having sufficient "verbal fluency"), with only three studies providing reasons for excluding patients on language grounds. CONCLUSIONS: There was considerable variability across studies in the inclusion of ethnic minority patients in RCTs, with higher participation rates in countries with legislation to mandate their inclusion (eg, United States) than in those without such legislation (eg, United Kingdom). Less than 25% of the RCTs recruited a sizeable proportion of ethnic minorities, which raises concerns about external validity. The lack of objective measures or common procedures for assessing language proficiency across trials implies that language related eligibility decisions are often based on trial recruiters' impressionistic judgments, which could be subject to bias. The variability and inconsistent reporting on ethnicity and other socioeconomic factors in descriptions of research participants could be more specifically emphasized in trial reporting guidelines to promote best practice. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews: CRD42015024899; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015024899 (Archived by WebCite at http://www.webcitation.org/6kQmI2bdF). PMID- 27670362 TI - Weight-for-length/height growth curves for children and adolescents in China in comparison with body mass index in prevalence estimates of malnutrition. AB - BACKGROUND: It is important to update weight-for-length/height growth curves in China and re-examine their performance in screening malnutrition. AIM: To develop weight-for-length/height growth curves for Chinese children and adolescents. SUBJECTS AND METHODS: A total of 94 302 children aged 0-19 years with complete sex, age, weight and length/height data were obtained from two cross-sectional large-scaled national surveys in China. Weight-for-length/height growth curves were constructed using the LMS method before and after average spermarcheal/menarcheal ages, respectively. Screening performance in prevalence estimates of wasting, overweight and obesity was compared between weight-for height and body mass index (BMI) criteria based on a test population of 21 416 children aged 3-18. RESULTS: The smoothed weight-for-length percentiles and Z scores growth curves with length 46-110 cm for both sexes and weight-for-height with height 70-180 cm for boys and 70-170 cm for girls were established. The weight-for-height and BMI-for-age had strong correlation in screening wasting, overweight and obesity in each age-sex group. There was no striking difference in prevalence estimates of wasting, overweight and obesity between two indicators except for obesity prevalence at ages 6-11. CONCLUSION: This set of smoothed weight-for-length/height growth curves may be useful in assessing nutritional status from infants to post-pubertal adolescents. PMID- 27670364 TI - Single-Electron-Transfer Strategy for Reductive Radical Cyclization: Fe(CO)5 and Phenanthroline System. AB - An electron-transfer strategy using low-valent iron pentacarbonyl [Fe(CO)5] to generate radical species from alkyl iodides was achieved. A range of pyrrolidines, tetrahydrofurans, and carbocycles were synthesized via 5-exo cyclization reactions of alkyl radical intermediates generated by electron transfer from a system involving Fe(CO)5, 1,10-phenanthroline, and diisopropylamine. Moreover, tandem addition reactions with Michael acceptors were also explored. Photophysical and electrochemical studies support a mechanism that involves electron transfer from the low-valent Fe reductant to alkyl iodide. PMID- 27670367 TI - B cells: Genomic reorganization in germinal centres. PMID- 27670366 TI - Parasites and invasions: changes in gastrointestinal helminth assemblages in invasive and native rodents in Senegal. AB - Understanding why some exotic species become widespread and abundant in their colonised range is a fundamental issue that still needs to be addressed. Among many hypotheses, newly established host populations may benefit from a parasite loss ("enemy release" hypothesis) through impoverishment of their original parasite communities or reduced infection levels. Moreover, the fitness of competing native hosts may be negatively affected by the acquisition of exotic taxa from invaders ("parasite spillover") and/or by an increased transmission risk of native parasites due to their amplification by invaders ("parasite spillback"). We focused on gastrointestinal helminth communities to determine whether these predictions could explain the ongoing invasion success of the commensal house mouse (Mus musculus domesticus) and black rat (Rattus rattus), as well as the associated decrease in native Mastomys spp., in Senegal. For both invasive species, our results were consistent with the predictions of the enemy release hypothesis. A decrease in overall gastrointestinal helminth prevalence and infracommunity species richness was observed along the invasion gradients as well as lower specific prevalence/abundance (Aspiculuris tetraptera in Mus musculus domesticus, Hymenolepis diminuta in Rattus rattus) on the invasion fronts. Conversely, we did not find strong evidence of GIH spillover or spillback in invasion fronts, where native and invasive rodents co-occurred. Further experimental research is needed to determine whether and how the loss of gastrointestinal helminths and reduced infection levels along invasion routes may result in any advantageous effects on invader fitness and competitive advantage. PMID- 27670368 TI - Immunometabolism: Feast or famine to combat infection. PMID- 27670365 TI - Severe malaria: what's new on the pathogenesis front? AB - Plasmodium falciparum causes the most severe and fatal form of malaria in humans with over half a million deaths each year. Cerebral malaria, a complex neurological syndrome of severe falciparum malaria, is often fatal and represents a major public health burden. Despite vigorous efforts, the pathophysiology of cerebral malaria remains to be elucidated, thereby hindering the development of adjunctive therapies. In recent years, multidisciplinary and collaborative approaches have led to groundbreaking progress both in the laboratory and in the field. Here we review the latest breakthroughs in severe malaria pathogenesis, with a specific focus on new pathogenetic mechanisms leading to cerebral malaria. The most recent findings point towards specific parasite phenotypes targeting brain microvasculature, endothelial dysfunction and subsequent oedema-induced brain swelling. PMID- 27670369 TI - Simultaneous quantification of gatifloxacin, moxifloxacin, and besifloxacin concentrations in cornea and aqueous humor by LC-QTOF/MS after topical ocular dosing. AB - The fourth-generation fluoroquinolones are widely used as ophthalmic antimicrobials. This study aimed to validate a new analytical technique for simultaneous quantification of gatifloxacin, moxifloxacin, and besifloxacin concentrations in the cornea and aqueous humor by liquid chromatography (LC) coupled to quadrupole time-of-flight mass spectrometry (QTOF/MS) at 10min and 1h after instillation of topical ophthalmic antimicrobial suspensions. It was used twenty-two male dogs without ocular lesions verified by ophthalmic and histologic examinations. Methanol:water (4:1) was used for the extraction procedure for cornea and acetonitrile:water (4:1) was used for aqueous humor. The chromatographic separations were carried out on a C18 column with a linear gradient of water and methanol, both containing 0.1% formic acid. The total chromatographic run time was 4min. Mass spectrometry analyses were performed on a XevoTM G2-S QTof tandem mass spectrometer, operated in a positive ion electrospray ionization (ESI+) mode. The retention times were approximately 1.42min for gatifloxacin, 1.87min for moxifloxacin, and 3.01min for besifloxacin. No interference peak was detected for the three tested antimicrobials in samples obtained from both cornea and aqueous humor, ensuring that the peak response was exclusive to the analyte of interest. The limit of detection for the three antimicrobials was 0.11MUg/mL and the limit of quantification was 0.42MUg/mL for both cornea and aqueous humor samples. At both time points post instillation of the three antimicrobials, moxifloxacin had the highest corneal concentration and besifloxacin demonstrated the highest concentration in the aqueous humor. PMID- 27670370 TI - Rehabilitation of irradiated patients with chemically modified and conventional SLA implants: a clinical clarification. PMID- 27670371 TI - Synergistic killing by meropenem and colistin combination of carbapenem-resistant Acinetobacter baumannii isolates from Chinese patients in an in vitro pharmacokinetic/pharmacodynamic model. AB - Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important clinical threat. Combination therapy that exerts a synergistic effect has become a potential solution to combat CRAB. However, choosing an optimal combination regimen is challenging. A dynamic in vitro pharmacokinetic/pharmacodynamic (PK/PD) model that can simulate the pharmacokinetic profiles of antibiotics provides a powerful tool to compare antibacterial responses to different clinical dosage regimens. In this study, the synergistic effect of the combination of meropenem and colistin was tested in 12 clinical CRAB isolates from Chinese patients using the chequerboard technique. The antibacterial effect was investigated in an in vitro PK/PD diffusion model by simulating different dosage regimens: meropenem monotherapy (0.5 g with 0.5-h infusion or 1 g with 3-h infusion); colistin monotherapy (fixed unbound concentration maintained at 0.25, 0.5 or 1 mg/L); and combination of meropenem and colistin. The chequerboard method showed that the combination of meropenem and colistin had synergistic effects against all 12 isolates, with fractional inhibitory concentration indices (FICIs) of <=0.5. Moreover, the dynamic in vitro PK/PD model demonstrated that for clinical CRAB isolates with a meropenem MIC of 128 mg/L, the combination (meropenem 1 g with 3-h infusion combined with colistin maintained at 1 mg/L) could achieve 3.8 log10 killing after 24 h, whereas monotherapy was unable to provide such an antibacterial effect. Taken together, these results suggest that the combination of meropenem and colistin might be a promising therapy against CRAB. PMID- 27670372 TI - Just how high-risk are ongoing smokers? Exploring clusters of health risk behaviours among current and ex-smokers. AB - There is limited research about the patterns of multiple health risks among smokers, despite the associated increased risk of poor health. This study aimed to identify which risk behaviours were evident in a sample of smokers and ex smokers who had previously been offered cessation support. A cross-sectional telephone interview in 2013 involved participants from New South Wales, Australia, from the control condition (self-help materials only) of a randomised smoking cessation trial conducted approximately five years earlier. The interview assessed smoking, weight, height, fruit and vegetable intake, physical activity, alcohol intake and depression. Of the 626 eligible participants, 321 were interviewed (consent rate=85.6%, response rate=51.3%); 62% were current smokers. Most participants (57%) reported four or five health risk behaviours. Three risk clusters were identified using latent class analysis: i) 'high risk' (42% of sample): smokers, overweight, inadequate intake of fruit and vegetables and low levels of physical activity; ii) 'lower risk non-depressed' (22% of sample): adequate physical activity and an absence of depression; and iii) 'lower risk, low alcohol' (36% of sample): low alcohol consumption, overweight and depressed. Males and current smokers were more likely to be 'high risk', while women and ex smokers were more likely to be members of the 'lower risk, low alcohol' cluster. Those who continue to smoke have multiple additional health risks; as do ex smokers in the 'lower risk, low alcohol' cluster. Achieving good health outcomes for these sizeable groups will require tailored, intensive or case-management approaches which can address multiple health risk behaviours. PMID- 27670373 TI - Real-world risk score for hepatocellular carcinoma risk prediction in CHBV: a validation outside of Asia. PMID- 27670374 TI - Inhibition of RAF1 kinase activity restores apicobasal polarity and impairs tumour growth in human colorectal cancer. AB - BACKGROUND AND AIM: Colorectal cancer (CRC) remains one of the leading causes of cancer-related death. Novel therapeutics are urgently needed, especially for tumours with activating mutations in KRAS (~40%). Here we investigated the role of RAF1 in CRC, as a potential, novel target. METHODS: Colonosphere cultures were established from human tumour specimens obtained from patients who underwent colon or liver resection for primary or metastatic adenocarcinoma. The role of RAF1 was tested by generating knockdowns (KDs) using three independent shRNA constructs or by using RAF1-kinase inhibitor GW5074. Clone-initiating and tumour initiating capacities were assessed by single-cell cloning and injecting CRC cells into immune-deficient mice. Expression of tight junction (TJ) proteins, localisation of polarity proteins and activation of MEK-ERK pathway was analysed by western blot, immunohistochemistry and immunofluorescence. RESULTS: KD or pharmacological inhibition of RAF1 significantly decreased clone-forming and tumour-forming capacity of all CRC cultures tested, including KRAS-mutants. This was not due to cytotoxicity but, at least in part, to differentiation of tumour cells into goblet-like cells. Inhibition of RAF1-kinase activity restored apicobasal polarity and the formation of TJs in vitro and in vivo, without reducing MEK-ERK phosphorylation. MEK-inhibition failed to restore polarity and TJs. Moreover, RAF1-impaired tumours were characterised by normalised tissue architecture. CONCLUSIONS: RAF1 plays a critical role in maintaining the transformed phenotype of CRC cells, including those with mutated KRAS. The effects of RAF1 are kinase-dependent, but MEK-independent. Despite the lack of activating mutations in RAF1, its kinase domain is an attractive therapeutic target for CRC. PMID- 27670375 TI - First-line Helicobacter pylori eradication therapies in countries with high and low clarithromycin resistance: a systematic review and network meta-analysis. AB - OBJECTIVE: To determine the optimal regimen of different first-line Helicobacter pylori eradication therapies according to the clarithromycin resistance rate. DESIGN: Electronic search for articles published between January 2005 and April 2016. Randomised, controlled trials that reported the effectiveness of first-line eradication therapies in treatment-naive adults were included. Two independent reviewers performed articles screening and data extraction. Network and traditional meta-analyses were conducted using the random effect model. Subgroup analyses were performed to determine the ranking of regimens in countries with high (>15%) and low (<15%) clarithromycin resistance. Data including adverse events and therapeutic cure rate were also extracted and analysed. RESULTS: 117 trials (totally 32 852 patients) for 17 H. pylori eradication regimens were eligible for inclusion. Compared with 7-day clarithromycin-based triple therapy, sequential therapy (ST) for 14 days had the highest effectiveness (OR=3.74, 95% CrI 2.37 to 5.96). ST-14 (OR=6.53, 95% CrI 3.23 to 13.63) and hybrid therapy (HY) for 10 days or more (OR=2.85, 95% CrI 1.58 to 5.37) represented the most effective regimen in areas with high and low clarithromycin resistance, respectively. The effectiveness of standard triple therapy was below therapeutic eradication rate in most of the countries. Longer duration was associated with higher eradication rate, but with a higher risk of events that lead to discontinuation. CONCLUSIONS: ST and HY appeared to be the most effective therapies in countries with high and low clarithromycin resistance, respectively. The clinical decision for optimal regimen can be supported by referring to the rank ordering of relative efficacies stratified by local eradication rates, antibiotic resistance and safety profile. TRIAL REGISTRATION NUMBER: CRD42015025445. PMID- 27670376 TI - Characterisation of the faecal microbiota in Japanese patients with paediatric onset primary sclerosing cholangitis. PMID- 27670377 TI - Ecogeographic variation across morphofunctional units of the human nose. AB - OBJECTIVES: Although the internal nose is overwhelmingly responsible for heat and moisture exchange during respiration, external nasal morphology is more commonly cited as evincing climatic adaptation in humans. Here, we assess variation across all four morphofunctional units of the complete nasorespiratory tract (external pyramid, nasal aperture, internal nasal fossa, and nasopharynx) to determine which units provide the strongest evidence of climatic adaptation. MATERIALS AND METHODS: We employ 20 linear measurements collected on 837 modern human crania from major geographic (Arctic Circle, Asia, Australia, Europe, Africa) and climatic (polar, temperate, hot-arid, tropical) zones. In conjunction with associated climatic and geographic data, these morphological data are employed in multivariate analyses to evaluate the associations between each of these functional nasal units and climate. RESULTS: The external pyramid and nasopharynx exhibit virtually no evidence of climate-mediated morphology across the regional samples, while apparent associations between climate and nasal aperture morphology appear influenced by the geographic (and likely genetic) proximities of certain populations. Only the internal nasal fossa exhibits an ecogeographic distribution consistent with climatic adaptation, with crania from colder and/or drier environments displaying internal nasal fossae that are longer, taller, and narrower (especially superiorly) compared to those from hotter and more humid environments. CONCLUSIONS: Our study indicates that the internal nasal fossa exhibits a stronger association with climate compared to other aspects of the human nose. Further, our study supports suggestions that regional variation in internal nasal fossa morphology reflects demands for heat and moisture exchange via adjustment of internal nasal airway dimensions. Our study thus provides empirical support for theoretical assertions related to nasorespiratory function, with important implications for understanding human nasal evolution. PMID- 27670378 TI - Highly sensitive visible to infrared MoTe2 photodetectors enhanced by the photogating effect. AB - Two-dimensional materials are promising candidates for electronic and optoelectronic applications. MoTe2 has an appropriate bandgap for both visible and infrared light photodetection. Here we fabricate a high-performance photodetector based on few-layer MoTe2. Raman spectral properties have been studied for different thicknesses of MoTe2. The photodetector based on few-layer MoTe2 exhibits broad spectral range photodetection (0.6-1.55 MUm) and a stable and fast photoresponse. The detectivity is calculated to be 3.1 * 10(9) cm Hz(1/2) W(-1) for 637 nm light and 1.3 * 10(9) cm Hz(1/2) W(-1) for 1060 nm light at a backgate voltage of 10 V. The mechanisms of photocurrent generation have been analyzed in detail, and it is considered that a photogating effect plays an important role in photodetection. The appreciable performance and detection over a broad spectral range make it a promising material for high-performance photodetectors. PMID- 27670379 TI - Opening our eyes to a critical approach to medicine: The humanities in medical education. AB - This paper examines a recent medical graduate's perspective on how undergraduate education tends to focus on imparting medical knowledge with little reference to the human aspects in clinical medicine. This is problematic because medicine is both about people and practiced by people. Students often have minimal exposure to the humanities prior to and in medical school and are frequently unaware of the societal trends that impact their view of medical practice. Familiarity with the humanities is a crucial means to understanding human nature, recognizing personal sociocultural biases, and practicing patient-centered medicine. This gap in knowledge may be due to the increase in medical information and optimistic ideologies related to medical progress. Philosophical paradigms and historical examples are considered to demonstrate the relevance of both fields in the humanities in understanding the role of moral human agents in applying medical knowledge. Educational changes in the humanities are proposed as a potential solution to our current deficits. Informal changes include mentorship relationships and shifting the general underpinning attitude in medical culture. Formal changes include specific courses teaching a critical approach to medicine. Changes in competency-based education and admissions are also suggested. These amendments are proposed to practice a fuller, truly human medicine. PMID- 27670380 TI - Secondary Sclerosing Cholangitis From Spontaneous Choledochoduodenal Fistula. PMID- 27670381 TI - Biomarkers of Reflux Disease. PMID- 27670382 TI - Level of Fecal Calprotectin and the Severity of Small Bowel Crohn's Disease. PMID- 27670383 TI - HCV Resistance Profile Evolution in a GT1b, DAA-Naive Patient Before, On, and After Failing Triple DAA Therapy. PMID- 27670384 TI - More Questions Than Answers: Comparison of the Risk of Cardiopulmonary Adverse Events Between Propofol and Traditional Anesthesia for Gastrointestinal Endoscopy. PMID- 27670386 TI - Effect of reciprocating agitation thermal processing (RA-TP) on quality of canned tomato (Solanum lycopersicum) puree. AB - BACKGROUND: Reciprocating agitation thermal processing (RA-TP) is a recent innovation in the field of canning for obtaining high-quality canned food. The objective of this study was to compare RA-TP processing with conventional non agitated (still) processing with respect to the impact on quality (color, antioxidant capacity, total phenols, carotenoid and lycopene contents) of canned tomato (Solanum lycopersicum) puree. RESULTS: Owing to a 63-81% reduction in process times as compared with still processing, tomato puree with a brighter red color (closer to fresh) was obtained during RA-TP. At 3 Hz reciprocation frequency, the loss of antioxidant, lycopene and carotenoid contents could be reduced to 34, 8 and 8% respectively as compared with 96, 41 and 52% respectively during still processing. In fact, the phenolic content for RA-TP at 3 Hz was 5% higher than in fresh puree. Quality retention generally increased with an increase in frequency, although the differences were less significant at higher reciprocation frequencies (between 2 and 3 Hz). CONCLUSION: Research findings indicate that RA-TP can be effective to obtain thermally processed foods with high-quality attribute retention. It can also be concluded that a very high reciprocation frequency (>3 Hz) is not necessarily needed and significant quality improvement can be obtained at lower frequencies (~2 Hz). (c) 2016 Society of Chemical Industry. PMID- 27670387 TI - A roller-like bird (Coracii) from the Early Eocene of Denmark. AB - The fossil record of crown group birds (Neornithes) prior to the Cretaceous Paleogene boundary is scarce and fragmentary. Early Cenozoic bird fossils are more abundant, but are typically disarticulated and/or flattened. Here we report the oldest roller (Coracii), Septencoracias morsensis gen. et sp. nov. (Primobucconidae), based on a new specimen from the Early Eocene (about 54 million years ago) Fur Formation of Denmark. The new fossil is a nearly complete, three-dimensionally preserved and articulated skeleton. It lies at the lower end of the size range for extant rollers. Salient diagnostic features of Septencoracias relative to other Coracii include the proportionally larger skull and the small, ovoid and dorsally positioned narial openings. Our discovery adds to the evidence that the Coracii had a widespread northern hemisphere distribution in the Eocene. Septencoracias is the oldest substantial record of the Picocoraciae and provides a reliable calibration point for molecular phylogenetic studies. PMID- 27670385 TI - Detection of cerebral NAD+ in humans at 7T. AB - PURPOSE: To develop 1 H-based MR detection of nicotinamide adenine dinucleotide (NAD+ ) in the human brain at 7T and validate the 1 H results with NAD+ detection based on 31 P-MRS. METHODS: 1 H-MR detection of NAD+ was achieved with a one dimensional double-spin-echo method on a slice parallel to the surface coil transceiver. Perturbation of the water resonance was avoided through the use of frequency-selective excitation. 31 P-MR detection of NAD+ was performed with an unlocalized pulse-acquire sequence. RESULTS: Both 1 H- and 31 P-MRS allowed the detection of NAD+ signals on every subject in 16 min. Spectral fitting provided an NAD+ concentration of 107 +/- 28 MUM for 1 H-MRS and 367 +/- 78 MUM and 312 +/ 65 MUM for 31 P-MRS when uridine diphosphate glucose (UDPG) was excluded and included, respectively, as an overlapping signal. CONCLUSIONS: NAD+ detection by 1 H-MRS is a simple method that comes at the price of reduced NMR visibility. NAD+ detection by 31 P-MRS has near-complete NMR visibility, but it is complicated by spectral overlap with NADH and UDPG. Overall, the 1 H- and 31 P-MR methods both provide exciting opportunities to study NAD+ metabolism on human brain in vivo. (c) 2016 International Society for Magnetic Resonance in Medicine. Magn Reson Med 78:828-835, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27670388 TI - The comparative efficacy of kinesio taping and local injection therapy in patients with subacromial impingement syndrome. AB - OBJECTIVE: The aim of this study was to compare the therapeutic effects of kinesio taping (KT) and local subacromial injection in patients with subacromial impingement, syndrome (SIS) with regard to pain, range of motion (ROM) and disability. METHODS: Sixty-one patients (48 females and 13 males; mean age: 43.04 +/- 6.31, years) with SIS were enrolled into the study. The patients were randomized into two treatment groups receiving either a single corticosteroid and local anesthetic (LA) injection, or kinesio taping performed three times by intervals of 3 day. Visual analog scale (VAS) was used to assess pain intensity, range of motion (ROM) degrees of, shoulder were recorded and Shoulder Pain and Disability Index (SPADI) was, performed to evaluate functional disability, before treatment, at the first and fourth, weeks after therapies. A exercise program was prescribed for both groups including pendulum, active range of motion (ROM) and strengthening exercises. RESULTS: Pain, functional outcome measures were determined to have improved significantly in both groups at the end of therapies at first and fourth weeks (p < 0.05), but these improvements were more significant in the injection group than in kinesio taping group (p < 0.05). The improvements in pain at rest, shoulder abduction degrees, and SPADI scores at first and fourth weeks were statistically higher in injection group than in kinesio taping group. CONCLUSION: Although the improvement in pain intensity at rest, ROM and disability were better with local injection, KT may be an alternative noninvasive method to local subacromial injection for patients suffering from subacromial impingement syndrome. LEVEL OF EVIDENCE: Level I, Therapeutic study. PMID- 27670389 TI - G Protein-Coupled Receptors in Myelinating Glia. AB - The G protein-coupled receptor (GPCR) superfamily represents the largest class of functionally selective drug targets for disease modulation and therapy. GPCRs have been studied in great detail in central nervous system (CNS) neurons, but these important molecules have been relatively understudied in glia. In recent years, however, exciting new roles for GPCRs in glial cell biology have emerged. We focus here on the key roles of GPCRs in a specialized subset of glia, myelinating glia. We highlight recent work firmly establishing GPCRs as regulators of myelinating glial cell development and myelin repair. These advances expand our understanding of myelinating glial cell biology and underscore the utility of targeting GPCRs to promote myelin repair in human disease. PMID- 27670391 TI - Relationship between chronic kidney disease with diabetes or hypertension and frailty in community-dwelling Japanese older adults. AB - AIM: The aim of the present study was to evaluate the relationship between kidney function with concomitant diabetes or hypertension and frailty in community dwelling Japanese older adults. METHODS: The participants were 9606 residents (community-dwelling Japanese older adults) who completed baseline assessments. The estimated glomerular filtration rate (mL/min/1.73 m2 ) was determined according to the serum creatinine level, and participants were classified into four mutually exclusive categories: >=60.0 (normal range), 45.0-59.9, 30.0-44.9 and <30.0 mL/min/1.73 m2 . Frailty status was defined using five criteria as described by Fried: slow gait speed, muscle weakness, low physical activity, exhaustion and unintentional weight loss. Participants who met three, four or five criteria satisfied the definition of having frailty. Multivariate logistic regression was used to examine the relationships between estimated glomerular filtration rate and frailty. RESULTS: After multivariate adjustment, participants with lower kidney function (estimated glomerular filtration rate <30.0 mL/min/1.73 m2 ) were more frail (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.01-3.59). In addition, individuals with a history of diabetes (OR 2.76, 95% CI 1.21-8.24) or hypertension (OR 2.53, 95% CI 1.45-5.12) showed a significantly increased risk of frailty in the lower kidney function group, regardless of multivariate controls. Furthermore, the analyses showed an even greater increase in the risk of frailty in patients with a history of both diabetes and hypertension (OR 3.67, 95% CI 1.13-14.1) CONCLUSIONS: A lower level of kidney function was associated with a higher risk of frailty in community dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 1527-1533. PMID- 27670392 TI - Fatigue in early Parkinson's disease: the Norwegian ParkWest study. AB - BACKGROUND AND PURPOSE: Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD). The pathogenesis is unknown, and the treatment options are limited. The aim of the present study was to investigate the development of fatigue during the first year after diagnosis. METHODS: The study design was a prospective, controlled population-based longitudinal cohort study, comprising 181 de novo, drug-naive patients with PD and 162 control participants. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Both groups were assessed for fatigue at baseline and after 1 year. RESULTS: Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation. The FSS scores in the patient group improved from a mean score of 4.4 (SD 1.6) to 4.0 (SD 1.6). Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up. Patients who received dopamine agonists improved slightly more than patients who received levodopa. A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity, depressive symptoms, sleep problems, apathy or cognitive impairment. CONCLUSION: Fatigue is a common symptom in PD, also in early, untreated patients. During the first year of observation, an improvement in the fatigue scores was found. The improvement could not be attributed to a change in disease severity or depressive symptoms. The results indicate a better effect of dopamine agonists than of levodopa. This may have implications for treatment in patients with PD-associated fatigue. PMID- 27670393 TI - Response to tolvaptan and its effect on prognosis in cirrhotic patients with ascites. AB - AIM: The vasopressin V2 receptor antagonist tolvaptan has been used for the treatment of cirrhotic patients with ascites; however, no predictor of efficacy and prognosis has been developed. We evaluated candidate predictors of response to tolvaptan treatment. METHODS: This was a single-center retrospective study. Overall, 97 Japanese cirrhotic patients (60 men, median age 63 years), who were hospitalized for ascites treatment including oral tolvaptan coupled with conventional diuretics, were enrolled. The efficacy of tolvaptan was defined as a urination increase of >=500 mL or a urine volume >=2000 mL/day on the day following treatment. The prognosis of tolvaptan treatment was evaluated by the post-treatment survival time by Kaplan-Meier analysis. RESULTS: Tolvaptan therapy was effective in 67% of cirrhotic patients. Patients showed -1.5 (-17.2 to +6.2) kg change in body weight and 40% achieved >=2.0 kg reduction in body weight after 1 week of treatment. Platelet counts, urine sodium (Na) level, and urine Na/potassium (Na/K) ratio were higher, and the blood urea nitrogen (BUN)/creatinine (Cr) ratio was lower, in cases showing a response to tolvaptan. The combination of a BUN/Cr ratio >=17.5 and urine Na/K ratio <3.09 was predictive of being non-responsive to tolvaptan, and the response rate in these patients was only 39% (P < 0.01). The mean post-treatment survival duration was significantly longer in patients who responded to tolvaptan therapy. CONCLUSIONS: Urinary BUN and Na excretion were predictive of a response to tolvaptan, and tolvaptan treatment may improve the prognosis of cirrhotic patients. PMID- 27670390 TI - Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation. AB - Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between MU- and delta-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry. Because of the broad distribution of opioid systems, every brain cell may be touched by pass-forward allostasis in the opioid-dependent/tolerant state. We will implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs. PMID- 27670394 TI - Carbon monoxide shifts energetic metabolism from glycolysis to oxidative phosphorylation in endothelial cells. AB - Carbon monoxide (CO) modulates mitochondrial respiration, but the mechanisms involved are not completely understood. The aim of the present study was to investigate the acute effects of CO on bioenergetics and metabolism in intact EA.hy926 endothelial cells using live cell imaging techniques. Our findings indicate that CORM-401, a compound that liberates CO, reduces ATP production from glycolysis, and induces a mild mitochondrial depolarization. In addition, CO from CORM-401 increases mitochondrial calcium and activates complexes I and II. The subsequent increase in mitochondrial respiration leads to ATP production through oxidative phosphorylation. Thus, our results show that nonactivated endothelial cells rely primarily on glycolysis, but in the presence of CO, mitochondrial Ca2+ increases and activates respiration that shifts the metabolism of endothelial cells from glycolysis- to oxidative phosphorylation-dependent ATP production. PMID- 27670395 TI - Impact of serum and dialysates obtained from chronic hemodialysis patients maintained on high cut-off membranes on inflammation profile in human THP-1 monocytes. AB - INTRODUCTION: Patients with chronic kidney disease maintained on intermittent hemodialysis suffer from systemic chronic inflammation which is causally associated with high mortality. Inflammation mediators of 15-45 kDa range cannot be effectively removed by conventional dialysis membranes. In this study, we tested the influence of serum and dialysates obtained from patients maintained on High cut-off or High flux membranes on the inflammation profile of THP-1 monocytes. METHODS: THP-1 monocytes were treated with serum or dialysates obtained from patients maintained on High cut-off and High flux membranes within a randomized crossover pilot trial. Serum-treated cells were subjected to qPCR analyses with TaqMan probes specific for IL6, TNFa, osteopontin and osteocalcin, and transcriptional screening with Inflammatory Array. Apoptosis assay was performed flow cytometrically with 7-AAD and Annexin V staining. FINDINGS: Treatment of the cells with High cut-off serum led to significant reduction of TNFa and IL-6 expression as well as inflammation-related osteopontin and osteocalcin as compared to High flux membrane treatment. As a complementary finding, treatment with High cut-off dialysates induced a pro-apoptotic phenotype in the cells as demonstrated by a significantly increased percentage of 7-AAD and Annexin V positivity. Global screening of serum-treated cells revealed noticeably decreased inflammation profile under High cut-off serum as compared to High flux treatment. DISCUSSION: Taken together, these data demonstrate that High cut-off membranes eliminate a spectrum of mediators from serum into the dialysate that possess proinflammatory properties and may impair cellular viability. PMID- 27670396 TI - Primary Infarction of Breast Fibroadenoma in the Absence of Pregnancy or Lactation. PMID- 27670397 TI - Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients. AB - Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score >=7 (0 = "no pain" and 10 = "worst pain"). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P = 3.45 * 10-8; rs880143, P = 3.45 * 10-8; and rs7526880, P = 4.92 * 10-8), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC. PMID- 27670398 TI - Advancing the revolution in the behavioral treatment of obesity. PMID- 27670399 TI - One-year postpartum outcomes following a weight management intervention in pregnant women with obesity. AB - OBJECTIVE: This analysis was focused on 1-year maternal and infant follow-up of a randomized trial that tested a weight management intervention conducted during pregnancy. METHODS: One hundred fourteen women with obesity (mean BMI 36.7 kg/m(2) ) were randomly assigned at a mean of 15 weeks gestation to a weight management intervention or usual care control condition. The intervention ended at delivery and resulted in less gestational weight gain and a lower proportion of large-for-gestational-age newborns among intervention compared with control participants. The primary outcome at 12 months postpartum was maternal weight. Secondary outcomes included infant weight-for-age and weight-for-length z-scores. RESULTS: At 1 year, mothers in the intervention group weighed 96.3 +/- 18.6 kg and those in the control group 99.7 +/- 19.2 kg. There was no significant difference between groups in change in weight from randomization to 1 year postpartum (b = -0.47, 95% CI: -4.03 to 3.08). There was a significant main effect of group for infant weight-for-age z-scores (b = -0.40, 95% CI: -0.75 to 0.05) but not infant weight-for-length z-scores (b = -0.20, 95% CI: -0.59 to 0.20). CONCLUSIONS: A gestational weight management intervention did not influence maternal weight or infant weight-for-length at 1 year postpartum. Future studies may be warranted to determine whether extending prenatal interventions into the postpartum period would be beneficial for maternal and infant outcomes. PMID- 27670400 TI - Acceptance-based versus standard behavioral treatment for obesity: Results from the mind your health randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy, as well as potential moderators and mediators, of a revised acceptance-based behavioral treatment (ABT) for obesity, relative to standard behavioral treatment (SBT). METHODS: Participants with overweight and obesity (n = 190) were randomized to 25 sessions of ABT or SBT over 1 year. Primary outcome (weight), mediator, and moderator measurements were taken at baseline, 6 months, and/or 12 months, and weight was also measured every session. RESULTS: Participants assigned to ABT attained a significantly greater 12-month weight loss (13.3% +/- 0.83%) than did those assigned to SBT (9.8% +/- 0.87%; P = 0.005). A condition by quadratic time effect on session-by-session weights (P = 0.01) indicated that SBT had a shallower trajectory of weight loss followed by an upward deflection. ABT participants were also more likely to maintain a 10% weight loss at 12 months (64.0% vs. 48.9%; P = 0.04). No evidence of moderation was found. Results supported the mediating role of autonomous motivation and psychological acceptance of food-related urges. CONCLUSIONS: Behavioral weight loss outcomes can be improved by integrating self-regulation skills that are reflected in acceptance-based treatment, i.e., tolerating discomfort and reduction in pleasure, enacting commitment to valued behavior, and being mindfully aware during moments of decision-making. PMID- 27670401 TI - Do activity monitors increase physical activity in adults with overweight or obesity? A systematic review and meta-analysis. AB - OBJECTIVE: To systematically assess contemporary knowledge regarding behavioral physical activity interventions including an activity monitor (BPAI+) in adults with overweight or obesity. METHODS: PubMed/MEDLINE, Embase, CINAHL, PsycINFO, CENTRAL, and PEDro were searched for eligible full-text articles up to 1 July 2015. Studies eligible for inclusion were (randomized) controlled trials describing physical activity outcomes in adults with overweight or obesity. Methodological quality was independently assessed employing the Cochrane Collaboration's tool for risk of bias. RESULTS: Fourteen studies (1,157 participants) were included for systematic review and 11 for meta-analysis. A positive trend in BPAI+ effects on several measures of physical activity was ascertained compared with both wait list or usual care and behavioral physical activity interventions without an activity monitor (BPAI-). No convincing evidence of BPAI+ effectiveness on weight loss was found compared with BPAI-. CONCLUSIONS: Behavioral physical activity interventions with an activity monitor increase physical activity in adults with overweight or obesity. Also, adding an activity monitor to behavioral physical activity interventions appears to increase the effect on physical activity, although current evidence has not yet provided conclusive evidence for its effectiveness. PMID- 27670402 TI - Changes in adiposity in an older Chinese population in rapid economic transition. AB - OBJECTIVE: To examine the changes in body mass index (BMI) and waist circumference (WC) in Guangzhou, South China, which is probably experiencing the most rapid economic transition in history. METHODS: In this study, 17,786 Chinese aged 50+ years were recruited from 2003 to 2008 and followed up until 2012. BMI and WC were measured at two time points. RESULTS: During the mean follow-up of 3.6 years (median = 3, interquartile = 1), age-adjusted mean BMI increased only slightly. By contrast, mean WC increased sharply by 0.94 cm (95% confidence interval 0.93-0.94) annually in men and 1.29 cm (1.28-1.29) annually in women. In 77% of women and 69% of men, WC increased, and among them, the mean annual increase was 2.01 cm and 1.70 cm, respectively. Among healthy, never-smoking participants, the incidence of central obesity was 29.0% (36.4% in women and 14.2% in men). The incidence of general obesity was 1.9% and was similarly low in both men and women (2.1% vs. 1.8%). Conversely, 20.3% of individuals with general obesity became nonobese, and 12.8% of individuals with central obesity returned to normal. CONCLUSIONS: Central obesity has risen sharply in this cohort. Such increases may have been greatly underestimated previously and should form the basis of an even stronger warning for regions undergoing economic transitions in China and elsewhere. PMID- 27670403 TI - Erratum: Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin. PMID- 27670405 TI - Unexpected effects of the MIP-CreER transgene and tamoxifen on beta-cell growth in C57Bl6/J male mice. AB - Transgenic mouse models have been fundamental in the discovery of factors that regulate beta-cell development, mass, and function. Several groups have recently shown that some of these models display previously uncharacterized phenotypes due to the transgenic system itself. These include impaired islet function and increased beta-cell mass due to the presence of a human growth hormone (hGH) minigene as well as impaired beta-cell proliferation in response to tamoxifen (TM) administration. We aimed to determine how these systems impact beta-cell mass and proliferation during high fat diet (HFD). To this end, we utilized C57Bl6/J male MIP-CreER mice, which are known to express hGH, or wild-type (WT) mice treated with vehicle corn oil or TM In the absence of TM, MIP-CreER mice fed a chow diet have increased beta-cell mass due to hypertrophy, whereas replication is unchanged. Similarly, after 1 week on HFD, MIP-CreER mice have increased beta cell mass compared to WT, and this is due to hypertrophy rather than increased proliferation. To assess the impact of TM on beta-cell proliferation and mass, WT mice were treated with vehicle corn oil or TM and then fed a chow diet or HFD for 3 days. We observed that TM-treated mice have improved glucose homeostasis on chow diet but impaired beta-cell proliferation in response to 3 days HFD feeding. These results unveil additional complications associated with commonly used pancreas-specific mouse models. PMID- 27670404 TI - Metabolic programming of a beige adipocyte phenotype by genistein. AB - SCOPE: Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. METHODS AND RESULTS: We observed that application of genistein to 3T3-L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin, and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD-137 and UCP1). Transcripts with a role in adipocyte differentiation (Cebpbeta, Pgc1alpha, Sirt1) peaked at different times after application of genistein. These responses were not affected by the estrogen receptor (ER) antagonist fulvestrant, revealing that this action of genistein is not through the classical ER pathway. The Sirt1 inhibitor Ex-527 curtailed the genistein-mediated increase in UCP1 and Cebpbeta mRNA, revealing a role for Sirt1 in mediating the effect. Baseline oxygen consumption and the proportional contribution of proton leak to maximal respiratory capacity was greater for cells exposed to genistein, demonstrating greater mitochondrial uncoupling. CONCLUSIONS: We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease. PMID- 27670406 TI - The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels. AB - We tested the hypothesis that the anti-inflammatory actions of atrial natriuretic peptide (ANP) result from the modulation of leukocyte adhesion to inflamed endothelium and not solely ANP ligation of endothelial receptors to stabilize endothelial barrier function. We measured vascular permeability to albumin and accumulation of fluorescent neutrophils in a full-thickness skin wound on the flank of LysM-EGFP mice 24 h after formation. Vascular permeability in individually perfused rat mesenteric microvessels was also measured after leukocytes were washed out of the vessel lumen. Thrombin increased albumin permeability and increased the accumulation of neutrophils. The thrombin-induced inflammatory responses were attenuated by pretreating the wound with ANP (30 min). During pretreatment ANP did not lower permeability, but transiently increased baseline albumin permeability concomitant with the reduction in neutrophil accumulation. ANP did not attenuate acute increases in permeability to histamine and bradykinin in individually perfused rat microvessels. The hypothesis that anti-inflammatory actions of ANP depend solely on endothelial responses that stabilize the endothelial barrier is not supported by our results in either individually perfused microvessels in the absence of circulating leukocytes or the more chronic skin wound model. Our results conform to the alternate hypothesis that ANP modulates the interaction of leukocytes with the inflamed microvascular wall of the 24 h wound. Taken together with our previous observations that ANP reduces deformability of neutrophils and their strength of attachment, rolling, and transvascular migration, these observations provide the basis for additional investigations of ANP as an anti-inflammatory agent to modulate leukocyte-endothelial cell interactions. PMID- 27670407 TI - Serum lipase activity and concentration during intravenous infusions of GLP-1 and PYY3-36 and after ad libitum meal ingestion in overweight men. AB - To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double-blinded, placebo-controlled 4 arm crossover study (Body Mass Index (BMI): 29 +/- 3 kg/m2, age: 33 +/- 9 years). On separate days, the subjects received a 150-min intravenous infusion of either (1) 0.8 pmol/kg/min PYY3-36, (2) 1.0 pmol/kg/min GLP-1, (3) 1 + 2, or (4) placebo. Samples were collected throughout the infusion and after intake of an ad libitum meal for measurement of serum lipase. Serum lipase levels measured by enzyme-linked immunosorbent assay (ELISA) following mono-infusions of GLP-1 and PYY3-36 were comparable to serum lipase levels following placebo (P = 0.054 and P = 0.873, respectively). Following the co-infusion of GLP-1 and PYY3-36, serum lipase levels measured by ELISA decreased over time compared to placebo (P = 0.012). However, the between-group difference was not consistent when each time point was analyzed separately. On the placebo day, serum lipase levels measured by ELISA after an ad libitum meal rose slightly compared to the preprandial values (P = 0.003). There was strong correlation between serum lipase levels measured by ELISA and LIPC Lipase colorimetric assay (COBAS) (0.94 < r; <0.0001). Infusions of GLP-1 and PYY3-36, separately or in combination, did not increase serum lipase. However, a small increase in serum lipase may occur in response to a meal. PMID- 27670408 TI - Associations between measures of vascular structure and function and systemic circulating blood markers in humans. AB - Examination of relationships between systemic markers and functional measures of arterial structure and function may assist in determining alternative indices of vascular regulation and designing and evaluating interventions to improve arterial structure and function. Twenty young healthy individuals, 20 older healthy men, and 26 individuals with coronary artery disease (CAD), comprising a spectrum of vascular health, participated. Systemic markers of vascular structure and function included: pro-collagen type I C-peptide (PIP) - marker of collagen synthesis, C-telopeptide of type I collagen (CTX) - marker of collagen degradation, endothelin-1 (ET-1) - vasoconstrictor, and interleukin-6 (IL-6) - inflammatory marker. Functional measures of arterial structure and function included carotid artery distensibility and brachial artery flow-mediated dilation (FMD). Moderate positive relationships were observed between carotid distensibility and CTX and PIP (r = 0.57, P < 0.0001 and r = 0.47, P < 0.0001). A negative correlation exists between ET-1 and FMD (r = -0.44, P = 0.0004); however, no relationship was observed between IL-6 and FMD (P = 0.25). Over a broad range of vascular health, relationships were observed between markers of type I collagen turnover and arterial stiffness and between a marker of vasoconstriction and endothelial function. These results indicate that regulatory links, between the indices examined, exist. Therefore, monitoring systemic markers rather than functional vascular measures, may provide sufficient information about vascular health and should be considered in the design and evaluation of vascular interventions. PMID- 27670410 TI - Hyperosmolality regulates UT-A6 urea transporter expression in the Caco-2 cell line. AB - Gastrointestinal facilitative urea transporters play a significant role in the urea nitrogen salvaging process, which supports the symbiotic relationship between mammals and their gut microbial populations. UT-A6 urea transporters have been previously reported in the human gastrointestinal tract, specifically in the colon. As renal UT-A transporters can be regulated by external osmolality, this study investigated whether UT-A6 expression could also be regulated in this manner. Initial end-point RT-PCR experiments confirmed UT-A6 expression along the human gastrointestinal tract (colon > small intestine ? stomach) and also in the Caco-2 intestinal cell line. Using Caco-2 cells exposed for 24 hours to changed external osmotic conditions (from 350 to 250, 500, or 600 mOsm), end-point PCR suggested UT-A6 expression increased in hyperosmotic conditions. Using quantitative PCR, it was confirmed that 24 h exposure to 600 mOsm stimulated a significant ~15-fold increase in UT-A6 expression (P < 0.001, N = 5, ANOVA). Finally, inhibitory experiments suggested that protein kinase C and calcium were involved in this hyperosmotic-stimulated regulatory pathway. In conclusion, these data demonstrated UT-A6 expression was indeed regulated by external osmolality. The physiological significance of this regulatory process upon gastrointestinal urea transport has yet to be determined. PMID- 27670409 TI - Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone. AB - Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-beta methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1 deficient mice. With the exception of MIP-2, which was significantly lower in PAI 1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3. PMID- 27670411 TI - Inhibition of alveolar Na transport and LPS causes hypoxemia and pulmonary arterial vasoconstriction in ventilated rats. AB - Oxygen diffusion across the alveolar wall is compromised by low alveolar oxygen but also by pulmonary edema, and leads to hypoxemia and hypoxic pulmonary vasoconstriction (HPV). To test, whether inhibition of alveolar fluid reabsorption results in an increased pulmonary arterial pressure and whether this effect enhances HPV, we established a model, where anesthetized rats were ventilated with normoxic (21% O2) and hypoxic (13.5% O2) gas received aerosolized amiloride and lipopolisaccharide (LPS) to inhibit alveolar fluid reabsorption. Right ventricular systolic pressure (RVsP) was measured as an indicator of pulmonary arterial pressure. Oxygen pressure (PaO2) and saturation (SaO2) in femoral arterial blood served as indicator of oxygen diffusion across the alveolar wall. Aerosolized amiloride and bacterial LPS decreased PaO2 and SaO2 and increased RVsP even when animals were ventilated with normoxic gas. Ventilation with hypoxic gas decreased PaO2 by 35 mmHg and increased RVsP by 10 mmHg. However, combining hypoxia with amiloride and LPS did not aggravate the decrease in PaO2 and SaO2 and had no effect on the increase in RVsP relative to hypoxia alone. There was a direct relation between SaO2 and PaO2 and the RVsP under all experimental conditions. Two hours but not 1 h exposure to aerosolized amiloride and LPS in normoxia as well as hypoxia increased the lung wet-to-dry weight ratio indicating edema formation. Together these findings indicate that inhibition of alveolar reabsorption causes pulmonary edema, impairs oxygen diffusion across the alveolar wall, and leads to an increased pulmonary arterial pressure. PMID- 27670412 TI - When Is It Important to Measure Unbound Drug in Evaluating Nanomedicine Pharmacokinetics? AB - Nanoformulations have become important tools for modifying drug disposition, be it from the perspective of enabling prolonged drug release, protecting the drug molecule from metabolism, or achieving targeted delivery. When examining the in vivo pharmacokinetic properties of these formulations, most investigations either focus on systemic concentrations of total (encapsulated plus unencapsulated) drug, or concentrations of encapsulated and unencapsulated drug. However, it is rare to find studies that differentiate between protein-bound and unbound (free) forms of the unencapsulated drug. In light of the unique attributes of these formulations, we cannot simply assume it appropriate to rely upon the protein binding properties of the traditionally formulated or legacy drug when trying to define the pharmacokinetic or pharmacokinetic/pharmacodynamic characteristics of these nanoformulations. Therefore, this commentary explores reasons why it is important to consider not only unencapsulated drug, but also the portion of unencapsulated drug that is not bound to plasma proteins. Specifically, we highlight those situations when it may be necessary to include measurement of unencapsulated, unbound drug concentrations as part of the nanoformulation pharmacokinetic evaluation. PMID- 27670414 TI - Seasonal dynamics with compensatory effects regulate populations of tropical forest marsupials: a 16-year study. AB - The conditions that a population experiences during one season can affect the strength of density dependence in the following season. In the tropics, many populations face their biggest challenges in the dry season due to limited food and cold-dry conditions. Seasonal environmental changes can be especially problematic for small, short-lived, seasonally breeding endotherms. To investigate the effects of seasonality on population dynamics, we studied five marsupial species in the Brazilian Atlantic Forest, using a 16-year dataset. We tested if (1) compensatory density feedback is stronger in the dry season, due to the high population sizes and limited food; (2) lower temperatures and the overall abundance of small mammals negatively affect dry season population growth rates; and (3) rainfall, a proxy for food availability, is positively related to wet season population growth rates. Population growth rates were regressed against seasonal population sizes and exogenous variables, and analyzed with linear autoregressive models. Seasonal compensatory density feedback occurred in both seasons, with compensation processes in just one season being sufficient to allow population persistence. Rainfall and the overall abundance of small mammals had little influence on populations, while colder temperatures decreased population growth rate of smaller species in both seasons. Although the study marsupials share similar life histories and phylogeny, they varied with respect to the season when compensatory density feedback was strongest. Our results demonstrate that seasonality plays a key role in driving marsupial population dynamics, and highlight the need to account for seasonality in demographic studies even in tropical environments. PMID- 27670413 TI - A quantitative synthesis of the role of birds in carrying ticks and tick-borne pathogens in North America. AB - Birds play a central role in the ecology of tick-borne pathogens. They expand tick populations and pathogens across vast distances and serve as reservoirs that maintain and amplify transmission locally. Research into the role of birds for supporting ticks and tick-borne pathogens has largely been descriptive and focused in small areas. To expand inference beyond these studies, we conducted a quantitative review at the scale of North America to identify avian life history correlates of tick infestation and pathogen prevalence, calculate species-level indices of importance for carrying ticks, and identify research gaps limiting understanding of tick-borne pathogen transmission. Across studies, 78 of 162 bird species harbored ticks, yielding an infestation prevalence of 1981 of 38,929 birds (5.1 %). Avian foraging and migratory strategies interacted to influence infestation. Ground-foraging species, especially non-migratory ground foragers, were disproportionately likely to have high prevalence and intensity of tick infestation. Studies largely focused on Borrelia burgdorferi, the agent of Lyme disease, and non-migratory ground foragers were especially likely to carry B. burgdorferi-infected ticks, a finding that highlights the potential importance of resident birds in local pathogen transmission. Based on infestation indices, all "super-carrier" bird species were passerines. Vast interior areas of North America, many bird and tick species, and most tick-borne pathogens, remain understudied, and research is needed to address these gaps. More studies are needed that quantify tick host preferences, host competence, and spatiotemporal variation in pathogen prevalence and vector and host abundance. This information is crucial for predicting pathogen transmission dynamics under future global change. PMID- 27670415 TI - Exotic trees modify the thermal landscape and food resources for lizard communities. AB - Increasing numbers of invasive plant species are establishing around the globe, and these species frequently form dense stands that alter habitat structure in critical ways. Nevertheless, little is known about the mechanisms underlying the impacts of invasive alien plant species on native fauna. We first ask whether alien pine trees impact lizard species richness in the Cape Floristic Region of South Africa, a world-renowned biodiversity hotspot, by examining differences in lizard species richness, abundance, and diversity between native mountain fynbos and exotic pine tree-dominated habitats. We then examine two mutually non exclusive processes: (i) changes in the thermal quality of the habitat and (ii) changes in the availability of food resources, to explain differences in lizard assemblages among habitat types. Lizard richness, abundance, and diversity were greater in fynbos habitat than in fynbos heavily invaded by pine and in pine plantations. The thermal quality of the environment and food resources was consistently higher in native fynbos than in pine forests, but these responses were more varied when comparisons were made along an invasion gradient and among seasons. Our results suggest that management strategies must consider spatially and temporally detailed measurements of thermal regimes and resources to assess the impacts of invasive vegetation on reptile diversity. PMID- 27670416 TI - 'It's not all just about the dying'. Kaumatua Maori attitudes towards physician aid-in dying: A narrative enquiry. AB - AIM: To explore kaumatua attitudes towards physician aid-in dying, to gain a clear understanding of how such attitudes may influence and shape their expectations of medical care at the end of life and to assist health professionals in Aotearoa/New Zealand to address the healthcare needs of older Maori near the end of life. DESIGN: A kaupapa Maori consistent approach was undertaken. A systematic narrative technique was employed for the qualitative data analysis. Data were triangulated through independent data coding by three researchers (two of whom identified as Maori researchers), to ensure a robust and consistent method of analysis as well as adhering to a kaupapa Maori research approach. SETTING/PARTICIPANTS: Recruitment of participants was through kaumatua of Te Kupenga Hauora Maori (Maori leadership within the Faculty of Medical and Health Sciences), University of Auckland and local Auckland marae. Focus group or individual interviews (as per their preference) were undertaken with 20 Kaumatua from the Auckland region. RESULTS: Five closely interrelated themes were identified from kaumatua narratives regarding physician aid-in dying. These were (1) attitudes and understandings of physician aid-in dying, (2) influence of power, (3) significance of kawa, (4) whanau relationships and the (5) significance of wairua. CONCLUSION: The study demonstrated that for these kaumatua, medical practices that hasten death such as physician aid-in dying are 'not all just about the dying'. Tikanga and kawa are important processes and concepts to understand during death and dying, and whanau are central to such processes being respected by those involved in the dying process. These factors are so closely intertwined that they cannot be considered in separation of each other. PMID- 27670417 TI - 'The horse has bolted I suspect': A qualitative study of clinicians' attitudes and perceptions regarding palliative rehabilitation. AB - BACKGROUND: Palliative care patients have numerous rehabilitation needs that increase with disease progression. Palliative rehabilitation practices and perceptions of palliative medicine physicians towards the role of rehabilitation are largely unstudied. AIM: To explore palliative medicine physicians' attitudes and perceptions towards rehabilitation delivered within inpatient palliative care units. DESIGN: Qualitative study utilizing semi-structured interviews. Transcribed interviews were analysed using thematic analysis and major themes reported as results. PARTICIPANTS: Australian palliative medicine physicians working in inpatient palliative care units. RESULTS: In total, 20 physicians participated, representing specialist palliative care services across Australia. A total of 11 (55%) were males with an average of 12.5 years' experience working in palliative care. Most participants believed rehabilitation was an important aspect of palliative care; however, few felt adequate rehabilitation programmes were available. Participants varied in their concepts of what palliative rehabilitation entailed. The term rehabilitation was seen by some as helpful (fostering hope and aiding transitions) and by others to be misleading (creating unrealistic expectations). Four key themes emerged when describing physicians' attitudes, including (1) integrating rehabilitation within palliative care, (2) the intervention, (3) possibilities and (4) the message of rehabilitation. CONCLUSION: A lack of consensus exists among palliative medicine specialists regarding the definition and scope of palliative rehabilitation. Participants generally expressed a wish to offer enhanced rehabilitation interventions, however described resource and skill-set limitations as significant barriers. Further research is required to establish an evidence base for palliative rehabilitation, to support its acceptance and widespread integration within specialist inpatient palliative care. PMID- 27670419 TI - Moving from parent "consultant" to parent "collaborator": one pediatric research team's experience. AB - We share our experiences as academic physical therapists and parents of young people with cerebral palsy working together as a research team, describe and critically review how our working relationship has evolved and propose further enhancements to realize our shared vision. This manuscript is informed by a call for "family-centered research," transcripts of face-to-face meetings held over a period of 11/2 days, the INVOLVE document and our experiences over almost a decade, as well as other related literature. Authentic collaborative research partnerships between academic researchers and parents embodying trust, mutual respect and shared social responsibility take time and effort to develop and sustain. Rehabilitation research is more meaningful and may be more impactful when strong collaborative partnerships between researchers and health service users are in place. Implications for Rehabilitation Involving service users in rehabilitation research is important, but not without challenges. Attaining authentic collaboration requires face-to-face meetings, time, effort, and ongoing open communication. Research processes are superior and outcomes may be improved with service user involvement. Impact of research on rehabilitation practice is anticipated to be more meaningful with service user involvement. PMID- 27670418 TI - What cost components are relevant for economic evaluations of palliative care, and what approaches are used to measure these costs? A systematic review. AB - BACKGROUND: It is important to understand the costs of palliative and end-of-life care in order to inform decisions regarding cost allocation. However, economic research in palliative care is very limited and little is known about the range and extent of the costs that are involved in palliative care provision. AIM: To undertake a systematic review of the health and social care literature to determine the range of financial costs related to a palliative care approach and explore approaches used to measure these costs. DESIGN: A systematic review of empirical literature with thematic synthesis. Study quality was evaluated using the Weight of Evidence Framework. DATA SOURCES: The databases CINAHL, Cochrane, PsycINFO and Medline were searched from 1995 to November 2015 for empirical studies which presented data on the financial costs associated with palliative care. RESULTS: A total of 38 papers met our inclusion criteria. Components of palliative care costs were incurred within four broad domains: hospital care, community or home-based care, hospice care and informal care. These costs could be considered from the economic viewpoint of three providers: state or government, insurers/third-party/not-for-profit organisations and patient and family and/or society. A wide variety of costing approaches were used to derive costs. CONCLUSION: The evidence base regarding the economics of palliative care is sparse, particularly relating to the full economic costs of palliative care. Our review provides a framework for considering these costs from a variety of economic viewpoints; however, further research is required to develop and refine methodologies. PMID- 27670420 TI - Intraoperative magnetic resonance imaging. AB - Intraoperative magnetic resonance imaging is a widely accepted method for resection control of glial tumors. Increasingly, it is also used during the resection of skull base tumors. Several studies have independently demonstrated an increase in the extent of resection in these tumors with improved prognosis for the patients. Technical innovations combined with the easier operation of this imaging modality have led to its widespread implementation. The development of digital image processing has also brought other modalities such as ultrasound and computed tomography to the focus of skull base surgery. PMID- 27670421 TI - [Simulation of speech perception with cochlear implants : Influence of frequency and level of fundamental frequency components with electronic acoustic stimulation]. AB - BACKGROUND: After implantation of cochlear implants with hearing preservation for combined electronic acoustic stimulation (EAS), the residual acoustic hearing ability relays fundamental speech frequency information in the low frequency range. With the help of acoustic simulation of EAS hearing perception the impact of frequency and level fine structure of speech signals can be systematically examined. OBJECTIVE: The aim of this study was to measure the speech reception threshold (SRT) under various noise conditions with acoustic EAS simulation by variation of the frequency and level information of the fundamental frequency f0 of speech. The study was carried out to determine to what extent the SRT is impaired by modification of the f0 fine structure. MATERIAL AND METHODS: Using partial tone time pattern analysis an acoustic EAS simulation of the speech material from the Oldenburg sentence test (OLSA) was generated. In addition, determination of the f0 curve of the speech material was conducted. Subsequently, either the parameter frequency or level of f0 was fixed in order to remove one of the two fine contour information of the speech signal. The processed OLSA sentences were used to determine the SRT in background noise under various test conditions. The conditions "f0 fixed frequency" and "f0 fixed level" were tested under two different situations, under "amplitude modulated background noise" and "continuous background noise" conditions. A total of 24 subjects with normal hearing participated in the study. RESULTS: The SRT in background noise for the condition "f0 fixed frequency" was more favorable in continuous noise with 2.7 dB and in modulated noise with 0.8 dB compared to the condition "f0 fixed level" with 3.7 dB and 2.9 dB, respectively. DISCUSSION: In the simulation of speech perception with cochlear implants and acoustic components, the level information of the fundamental frequency had a stronger impact on speech intelligibility than the frequency information. The method of simulation of transmission of cochlear implants allows investigation of how various parameters influence speech intelligibility in subjects with normal hearing. PMID- 27670422 TI - [An update on tonsillotomy studies]. AB - BACKGROUND: Tonsillotomy procedures (TT) are being increasingly performed owing to the low postoperative morbidity compared with extracapsular tonsillectomy (TE). Patients may experience regrowth of tonsillar tissue or tonsillitis in the tonsillar remnants eventually resulting in a secondary tonsillectomy. OBJECTIVES: A review of the literature was undertaken to evaluate the current indications and contraindications, surgical instruments, risks of surgery, and the need for further research related to TT. MATERIAL AND METHODS: A search of the PubMed database was performed with the following terms: "tonsillotomy," "partial tonsillectomy," "subtotal tonsillectomy," "intracapsular tonsillectomy," "RFITT," and "tonsil ablation." Filters included language (English; German) and publication date (1960-2016). Articles were excluded if they were not related to tonsil surgery, did not provide clinical data, dealt with uncommon surgical techniques, or presented only data from polysomnographic studies. RESULTS: In all, 104 papers encompassing 97 studies and seven national surveys were eligible for analysis. In total, 13,270 patients had undergone TT and were compared with 11,485 patients after TE. Partial resection of the tonsils was most commonly accomplished with a microdebrider (51.5 %), and less frequently with coblation (20.5 %), radiofrequency (9.1 %), CO2 laser (6.6 %), or other surgical instruments. The age in the study groups ranged between 6 months and 78 years (median: 6.0 years). The prevailing indication for surgery was upper airway obstruction resulting from tonsillar hyperplasia with (n = 20) or without (n = 60) a history of tonsillits. In seven studies, TT was explicitly performed to resolve tonsillitis, while three authors did not specify the indication for surgery. The hemorrhage rate after TT was 0.2 % on average. CONCLUSION: TT is predominantly indicated for tonsillar hyperplasia, with or without tonsillitis. Restrictions related to age or surgical instruments are not reported in the literature data. Data concerning operation time, intraoperative bleeding, and outcome favor TT over TE. The median values for regrowth (3.0 %), postoperative tonsillitis (2.85 %), and secondary TE (1.37 %) emphasize the high success rate of TT. Further research utilizing a uniform terminology is mandatory to clarify the benefit of TT over TE in the long term and to resolve sleep-related breathing disorders resulting from tonsillar hyperplasia or tonsillitis. PMID- 27670423 TI - High selective pressure for Notch1 mutations that induce Myc in T-cell acute lymphoblastic leukemia. AB - Activating NOTCH1 mutations are frequent in human T-cell acute lymphoblastic leukemia (T-ALL) and Notch inhibitors (gamma-secretase inhibitors [GSIs]) have produced responses in patients with relapsed, refractory disease. However, sustained responses, although reported, are uncommon, suggesting that other pathways can substitute for Notch in T-ALL. To address this possibility, we first generated KrasG12D transgenic mice with T-cell-specific expression of the pan Notch inhibitor, dominant-negative Mastermind (DNMAML). These mice developed leukemia, but instead of accessing alternative oncogenic pathways, the tumor cells acquired Notch1 mutations and subsequently deleted DNMAML, reinforcing the notion that activated Notch1 is particularly transforming within the context of T cell progenitors. We next took a candidate approach to identify oncogenic pathways downstream of Notch, focusing on Myc and Akt, which are Notch targets in T-cell progenitors. KrasG12D mice transduced with Myc developed T-ALLs that were GSI-insensitive and lacked Notch1 mutations. In contrast, KrasG12D mice transduced with myristoylated AKT developed GSI-sensitive T-ALLs that acquired Notch1 mutations. Thus, Myc can substitute for Notch1 in leukemogenesis, whereas Akt cannot. These findings in primary tumors extend recent work using human T-ALL cell lines and xenografts and suggest that the Notch/Myc signaling axis is of predominant importance in understanding both the selective pressure for Notch mutations in T-ALL and response and resistance of T-ALL to Notch pathway inhibitors. PMID- 27670425 TI - New concepts for anticoagulant therapy in persons with hemophilia. PMID- 27670426 TI - Using rare earth elements to constrain particulate organic carbon flux in the East China Sea. AB - Fluxes of particulate organic carbon (POC) in the East China Sea (ECS) have been reported to decrease from the inner continental shelf towards the outer continental shelf. Recent research has shown that POC fluxes in the ECS may be overestimated due to active sediment resuspension. To better characterize the effect of sediment resuspension on particle fluxes in the ECS, rare earth elements (REEs) and organic carbon (OC) were used in separate two-member mixing models to evaluate trap-collected POC fluxes. The ratio of resuspended particles from sediments to total trap-collected particles in the ECS ranged from 82-94% using the OC mixing model, and 30-80% using the REEs mixing model, respectively. These results suggest that REEs may be better proxies for sediment resuspension than OC in high turbidity marginal seas because REEs do not appear to undergo degradation during particle sinking as compared to organic carbon. Our results suggest that REEs can be used as tracers to provide quantitative estimates of POC fluxes in marginal seas. PMID- 27670424 TI - Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma. AB - We recently reported a truncating deletion in the NFKBIE gene, which encodes IkappaBepsilon, a negative feedback regulator of NF-kappaB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy refractory (P = .022) and displayed inferior outcome compared with wild-type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy (P =022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P = .003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-kappaB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL. PMID- 27670427 TI - Cluster headache in Greece: an observational clinical and demographic study of 302 patients. AB - BACKGROUND: Cluster headache (CH) is considered the most excruciating primary headache syndrome; although much less prevalent than migraine, it is not rare as it affects more than 1/1000 people. While its clinical presentation is considered stereotypic, atypical features are often encountered. Internationally, cluster headache is often misdiagnosed, undertreated and mistreated. METHODS: We prospectively studied 302 CH patients, all examined by the same headache specialist. The aim of our study was to describe the demographic and clinical characteristics of CH patients in Greece and draw attention to under-management, under-treatment and mis-treatment often encountered in clinical practice; our purpose is to improve recognition and successful treatment of cluster patients by Greek neurologists and other physicians. RESULTS: In the present cohort, clinical characteristics of CH are similar to those described in other populations. Beyond the standard clinical characteristics, features like side shifts (12.6 %), location of maximal pain intensity outside the first trigeminal branch division (10.2 %), lack of autonomic features (7 %), presence of associated features of migraine and aggravation by physical activity (10 %) were encountered. Four out of five patients had consulted a physician prior to diagnosis. The median number of physicians seen prior to diagnosis was 3 and the median time to diagnosis was 5 years, though it improved for patients with recent onset. Chronic cluster headache, side shifts, pain location in the face or the back of the head and aggravation by physical activity were found, among others, to be statistically significantly related to delayed diagnosis or more physicians seen prior to diagnosis. Even properly diagnosed patients were often undertreated or mistreated. CONCLUSIONS: Cluster headache, in a large cohort of Greek patients, has the same phenotypic characteristics as described internationally. Uncommon clinical features do exist and physicians should be aware of those, since they may eventuate in diagnostic problems. Most CH patients in Greece remain misdiagnosed or undiagnosed for rather lengthy periods of time, but time to diagnosis has improved recently. Even after diagnosis, treatment received was suboptimal. PMID- 27670428 TI - Altered functional connectivity of the marginal division in migraine: a resting state fMRI study. AB - BACKGROUND: The marginal division of neostriatum (MrD) is a flat, pan-shaped zone between the neostriatum and the globus pallidus, and previous documents demonstrated that it was involved in the modulation of pain. The aim of this study is to investigate the roles of the MrD of the human brain in the chronicization migraine using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Conventional MRI, 3D structure images, and rs-fMRI were performed in 18 patients with episodic migraines (EM), 16 patients with chronic migraine (CM), 44 patients with medication overuse headache plus chronic migraine (MOH + CM), and 32 normal controls (NC). MrD was defined using manual delineation on structural images, and was selected as the seed to calculate the functional connectivity (FC). RESULTS: Compared with the NC group, the decreased FC of MrD was observed in the EM and CM groups, and increased FC of MrD was demonstrated in all patient groups. Compared with the EM group, the decreased FC of MrD was revealed in the CM and MOH + CM groups, and the increased FC occurred only in the CM group. Increased FC of MrD alone was observed in the MOH + CM group compared with that in the CM group. CONCLUSION: This study confirmed the double neuromodulation network of MrD in pain modulation and migraine chronicization; however, the mechanism requires further investigation. PMID- 27670429 TI - Phantom rectal sensations following abdominoperineal excision of the rectum (APER) and vertical rectus abdominis myocutaneous (VRAM) flap perineal reconstruction. AB - AIM: Phantom rectum is the sensation of an intact and/or functioning rectum, despite excision at surgery. Abdominoperineal excision of the rectum (APER) may be complemented by reconstructive operations and recently it was reported that patients undergoing APER and vertical rectus abdominis myocutaneous (VRAM) flap reconstruction are more prone to develop phantom sensations at an earlier timeframe and have more persistent symptoms than those who do not have perineal repairs. The aim of this study was to determine the prevalence of phantom rectal sensations in a cohort of these patients. METHOD: Patients who underwent APER and VRAM flap reconstruction for anorectal carcinomas were identified from May 2008 to July 2012. Patients completed a questionnaire evaluating their experience of rectal symptoms post-surgery. RESULTS: Thirty-four of 47 eligible patients were enrolled in the study. PR sensations were experienced by 50 % of patients, the majority of which (65 %) were present for >1 year. The commonest sensation reported was the feeling of faeces in a normal rectum (24 %). Disturbances in quality of life were apparent in 44 %; notably, sleep was affected, patients expressed increased feelings of stress/sadness, heightened levels of anxiety and limitation of daily activities as consequences of PR symptoms. Few patients sought medical advice. CONCLUSION: Fifty percent of patients experience PR sensations post-surgery, comparable with reported data for patients who have undergone APER alone. The addition of VRAM reconstruction does not significantly alter the prevalence of PR symptoms. This paper provides further evidence that phantom rectum occurs frequently and thus all patients undergoing excision of the rectum should be counselled appropriately. PMID- 27670430 TI - Spatio-temporal Models of Lymphangiogenesis in Wound Healing. AB - Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: (1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case and (2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here, we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature. PMID- 27670431 TI - Harnessing Intra-Host Strain Competition to Limit Antibiotic Resistance: Mathematical Model Results. AB - Antibiotic overuse has promoted the spread of antibiotic resistance. To compound the issue, treating individuals dually infected with antibiotic-resistant and antibiotic-vulnerable strains can make their infections completely resistant through competitive release. We formulate mathematical models of transmission dynamics accounting for dual infections and extensions accounting for lag times between infection and treatment or between cure and ending treatment. Analysis using the Next-Generation Matrix reveals how competition within hosts and the costs of resistance determine whether vulnerable and resistant strains persist, coexist, or drive each other to extinction. Invasion analysis predicts that treatment of dually infected cases will promote resistance. By varying antibiotic strength, the models suggest that physicians have two ways to achieve a particular resistance target: prescribe relatively weak antibiotics to everyone infected with an antibiotic-vulnerable strain or give more potent prescriptions to only those patients singly infected with the vulnerable strain after ruling out the possibility of them being dually infected with resistance. Through selectivity and moderation in antibiotic prescription, resistance might be limited. PMID- 27670432 TI - Protective effect of telomerase-based 16-mer peptide vaccine (GV1001) on inferior epigastric island skin flap survivability in ischaemia-reperfusion injury rat model. AB - BACKGROUND: Ischaemia-reperfusion injury (IRI) results in oxidative damage and a profound inflammatory reaction, leading to cell death. GV 1001 is a telomerase based 16-mer peptide vaccine developed against cancer. However, it has also been reported to possess antioxidant and anti-inflammatory properties. The aim of this study was to determine if GV 1001 can reduce the negative effects caused by IRI in a rat skin flap model owing to its anti-oxidant and anti-inflammatory properties. MATERIALS AND METHODS: In order to evaluate the effect of GV 1001, 5 * 5 cm2 inferior epigastric artery based island skin flaps were dissected in 39 8 week-old Sprague-Dawley rats weighing 220-270 g. The rats were divided into three groups: (I) non-ischaemic group; (II) IRI with saline; and (III) IRI with 10 mg GV 1001 treatment. Drugs were administered intra-muscularly directly before and after ischaemia. Flap survival area, neutrophil infiltration, cytokine levels (interleukin [IL]-1, IL-6, and tumour necrosis factor-alpha), malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured. Flap survivability was analysed at 7 days after surgery. RESULTS: Flap survival area was significantly larger in group III than in group II. Cytokine release level was also significantly lower in group III. Neutrophil infiltration grade, MDA level, and SOD activity slightly decreased in Group III; however, the changes were not statistically significant. CONCLUSION: These results imply that GV 1001 exerts a protective effect against IRI through antioxidant effects, reducing reactive oxygen species, and suppressing the inflammatory cascade. PMID- 27670434 TI - Erratum to: Revealing Both Sides of the Story: A Comparative Analysis of Mentors and Proteges Relational Perspectives. PMID- 27670433 TI - Application of Bioorganic Fertilizer Significantly Increased Apple Yields and Shaped Bacterial Community Structure in Orchard Soil. AB - Application of bioorganic fertilizers has been reported to improve crop yields and change soil bacterial community structure; however, little work has been done in apple orchard soils where the biological properties of the soils are being degraded due to long-term application of chemical fertilizers. In this study, we used Illumina-based sequencing approach to characterize the bacterial community in the 0-60-cm soil profile under different fertilizer regimes in the Loess Plateau. The experiment includes three treatments: (1) control without fertilization (CK); (2) application of chemical fertilizer (CF); and (3) application of bioorganic fertilizer and organic-inorganic mixed fertilizer (BOF). The results showed that the treatment BOF increased the apple yields by 114 and 67 % compared to the CK and CF treatments, respectively. The treatment BOF also increased the soil organic matter (SOM) by 22 and 16 % compared to the CK and CF treatments, respectively. The Illumina-based sequencing showed that Acidobacteria and Proteobacteria were the predominant phyla and Alphaproteobacteria and Gammaproteobacteria were the most abundant classes in the soil profile. The bacterial richness for ACE was increased after the addition of BOF. Compared to CK and CF treatments, BOF-treated soil revealed higher abundance of Proteobacteria, Alphaproteobacteria and Gammaproteobacteria, Rhizobiales, and Xanthomonadales while Acidobacteria, Gp7, Gp17, and Sphaerobacter were found in lower abundance throughout the soil profile. Bacterial community structure varied with soil depth under different fertilizer treatments, e.g., the bacterial richness, diversity, and the relative abundance of Verruccomicrobia, Candidatus Brocadiales, and Skermanella were decreased with the soil depth in all three treatments. Permutational multivariate analysis showed that the fertilizer regime was the major factor than soil depth in the variations of the bacterial community composition. Two groups, Lysobacter and Rhodospirillaceae, were found to be the significantly increased by the BOF addition and the genus Lysobacter may identify members of this group effective in biological control-based plant disease management and the members of family Rhodospirillaceae had an important role in fixing molecular nitrogen. These results strengthen the understanding of responses to the BOF and possible interactions within bacterial communities in soil that can be associated with disease suppression and the accumulation of carbon and nitrogen. The increase of apple yields after the application of BOF might be attributed to the fact that the application of BOF increased SOM, and soil total nitrogen, and changed the bacterial community by enriching Rhodospirillaceae, Alphaprotreobateria, and Proteobacteria. PMID- 27670435 TI - BK channel agonist represents a potential therapeutic approach for lysosomal storage diseases. AB - Efficient lysosomal Ca2+ release plays an essential role in lysosomal trafficking. We have recently shown that lysosomal big conductance Ca2+-activated potassium (BK) channel forms a physical and functional coupling with the lysosomal Ca2+ release channel Transient Receptor Potential Mucolipin-1 (TRPML1). BK and TRPML1 forms a positive feedback loop to facilitate lysosomal Ca2+ release and subsequent lysosome membrane trafficking. However, it is unclear whether the positive feedback mechanism is common for other lysosomal storage diseases (LSDs) and whether BK channel agonists rescue abnormal lysosomal storage in LSDs. In this study, we assessed the effect of BK agonist, NS1619 and NS11021 in a number of LSDs including NPC1, mild cases of mucolipidosis type IV (ML4) (TRPML1-F408?), Niemann-Pick type A (NPA) and Fabry disease. We found that TRPML1-mediated Ca2+ release was compromised in these LSDs. BK activation corrected the impaired Ca2+ release in these LSDs and successfully rescued the abnormal lysosomal storage of these diseases by promoting TRPML1-mediated lysosomal exocytosis. Our study suggests that BK channel activation stimulates the TRPML1-BK positive reinforcing loop to correct abnormal lysosomal storage in LSDs. Drugs targeting BK channel represent a potential therapeutic approach for LSDs. PMID- 27670436 TI - The Reproductive Ecology of Industrial Societies, Part I : Why Measuring Fertility Matters. AB - Is fertility relevant to evolutionary analyses conducted in modern industrial societies? This question has been the subject of a highly contentious debate, beginning in the late 1980s and continuing to this day. Researchers in both evolutionary and social sciences have argued that the measurement of fitness related traits (e.g., fertility) offers little insight into evolutionary processes, on the grounds that modern industrial environments differ so greatly from those of our ancestral past that our behavior can no longer be expected to be adaptive. In contrast, we argue that fertility measurements in industrial society are essential for a complete evolutionary analysis: in particular, such data can provide evidence for any putative adaptive mismatch between ancestral environments and those of the present day, and they can provide insight into the selection pressures currently operating on contemporary populations. Having made this positive case, we then go on to discuss some challenges of fertility-related analyses among industrialized populations, particularly those that involve large scale databases. These include "researcher degrees of freedom" (i.e., the choices made about which variables to analyze and how) and the different biases that may exist in such data. Despite these concerns, large datasets from multiple populations represent an excellent opportunity to test evolutionary hypotheses in great detail, enriching the evolutionary understanding of human behavior. PMID- 27670439 TI - Erratum to Barco et al. "Home treatment of patients with lowrisk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the Hot-PE Trial" (Thromb Haemost 2016; 116: 191-197). AB - [This corrects the article DOI: 10.1160/TH16-01-0004.]. PMID- 27670437 TI - The Reproductive Ecology of Industrial Societies, Part II : The Association between Wealth and Fertility. AB - Studies of the association between wealth and fertility in industrial populations have a rich history in the evolutionary literature, and they have been used to argue both for and against a behavioral ecological approach to explaining human variability. We consider that there are strong arguments in favor of measuring fertility (and proxies thereof) in industrial populations, not least because of the wide availability of large-scale secondary databases. Such data sources bring challenges as well as advantages, however. The purpose of this article is to illustrate these by examining the association between wealth and reproductive success in the United States, using the National Longitudinal Study of Youth 1979. We conduct a broad-based exploratory analysis of the relationship between wealth and fertility, employing both cross-sectional and longitudinal approaches, and multiple measures of both wealth (income and net worth) and fertility (lifetime reproductive success and transitions to first, second and third births). We highlight the kinds of decisions that have to be made regarding sample selection, along with the selection and construction of explanatory variables and control measures. Based on our analyses, we find a positive effect of both income and net worth on fertility for men, which is more pronounced for white men and for transitions to first and second births. Income tends to have a negative effect on fertility for women, while net worth is more likely to positively predict fertility. Different reproductive strategies among different groups within the same population highlight the complexity of the reproductive ecology of industrial societies. These results differ in a number of respects from other analyses using the same database. We suggest this reflects the impossibility of producing a definitive analysis, rather than a failure to identify the "correct" analytical strategy. Finally, we discuss how these findings inform us about (mal)adaptive decision-making. PMID- 27670438 TI - A scaffold-free surface culture of B16F10 murine melanoma cells based on magnetic levitation. AB - Multicellular spheroids are obtained in a variety of three-dimensional (3D) culture systems without the use of supporting scaffold. We present here a 3D culture method that resulted in a multicellular sheet under scaffold-free conditions. A floating disk-shaped 3D culture was prepared by magnetic levitation of B16F10 cells that has ingested Fe3O4-containing fibroin microspheres. The melanoma disk grew up to 19 mm in diameter and the thickness was ranged between 80 and 100 MUm. The 3D culture was filled with closely packed cells that were proliferating exponentially at a specific growth rate of u = 0.015 h-1. Approximately half of the cells were Ki-67 positive with no detectable levels of apoptotic or autophagic cells. However, the percentage of propidium iodide permeable cells was 8.5 +/- 1.2 %, which was probably due to physical damage in the cell membrane caused by Fe3O4-containing microspheres under a strong magnetic field. Melanin production increased by a factor of 3.0-3.7 in the 3D culture, due to an increased population of pigmented cells. This study presented a surface 3D culture of B16F10 cells without the use of a scaffold based on magnetic levitation. PMID- 27670441 TI - A giant cervicothoracic cord lipoma: an uncommon finding. PMID- 27670440 TI - Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial. AB - Despite the huge health and economic burden of migraine headache, few medications have been approved for its prophylactic treatment, most of which can potentially induce serious adverse effects. Coenzyme Q10 (CoQ10) is a supplement and has shown preliminary benefits in migraine prophylaxis. We aimed to assess this effect in an adult population. This is an open-label, parallel, add-on, match controlled trial. Eighty patients diagnosed with migraine headache based on International Headache Society criteria were allocated to receiving only their current preventive drugs or their current preventive drugs plus 100 mg CoQ10 daily, matching for their baseline characteristics, and were assessed for frequency and severity of attacks, and >=50 % reduction in attack frequency per month. Thirty-six and 37 patients were analyzed in CoQ10 and control groups, respectively. Number of attacks per month dropped significantly in the CoQ10 group (mean decrease: 1.6 vs. 0.5 among CoQ10 and control groups, respectively, p < 0.001). A significant reduction was also evident in the severity of headaches (mean decrease: 2.3 vs. 0.6 among CoQ10 and control groups, respectively, p < 0.001). For >=50 % reduction in the frequency of attacks per month, the number needed to treat was calculated as 1.6. No side effects for CoQ10 were observed. This study suggests that CoQ10 might reduce the frequency of headaches, and may also make them shorter in duration, and less severe, with a favorable safety profile. PMID- 27670442 TI - Contrast-associated transient cortical blindness: three cases with MRI and electrophysiology findings. AB - Transient cortical blindness (TCB) is a rare but striking complication following contrast agent injection. TCB might be secondary to a direct toxicity of the contrast agent, leading to an osmotic disruption of the blood-brain barrier (BBB), with a preferential involvement of the posterior circulation and occipital cortex. We report a series of three patients with contrast medium-associated TCB (intra-arterial injection of non-ionic contrast agent during diagnostic cerebral angiography for two of them and coronary angioplasty for the other one). In two patients, the magnetic resonance imaging (MRI) was unremarkable; in the other patient, typical MRI findings were observed, with FLAIR hyperintensities in the right occipital cortex and decreased apparent diffusions coefficient (ADC). Interestingly, this patient also presented posterior rhythmic epileptiform activities on electroencephalogram during the first 36 h. Visual evoked potentials (VEPs) showed normal retinal potential, but a massive destructuration of the later potentials of the cortical origin. To our knowledge, this is the first time that VEPs acquired during TCB are reported. We discuss these findings with respect to the pathophysiology of TCB. PMID- 27670443 TI - Effects of post-traumatic growth on the dorsolateral prefrontal cortex after a disaster. AB - The relating to others factor of post-traumatic growth (PTG), which involves mutual help and a strong sense of connection with humanity, is important for young people who are coping with stress. The prefrontal cortex (PFC), especially the dorsolateral PFC (DLPFC), may play an important role in post-traumatic stress disorder (PTSD) with regard to coping and resilience. We hypothesized that the neural correlates of PTG may be responsible for resilience to the correlates of PTSD. Our study tested this hypothesis by examining whether measures of PTG, particularly the measures of relating to others after a disaster, were associated with increased regional grey matter volume (rGMV) in the PFC by assessing individuals who had experienced the East Japan Great Earthquake. We calculated the delta-rGMV by subtracting the rGMV obtained 3 months before the disaster from the rGMV obtained after this disaster using voxel-based morphometry. The magnetic resonance imaging data obtained from 26 subjects (M/F: 21/5; age: 21.2 +/- 1.6 yrs.) showed that the total scores on a PTG inventory and the subscore for relating to others at the post-assessment were positively and significantly associated with the delta-rGMV in the right DLPFC. The DLPFC seems to be the main neural correlate of PTG. PMID- 27670444 TI - Small cell lung cancer growth is inhibited by miR-342 through its effect of the target gene IA-2. AB - BACKGROUND: Small cell lung cancers (SCLC) are tumors of neuroendocrine origin. Previous in vitro studies from our laboratory showed that SCLC expresses high levels of the transmembrane dense core vesicle protein IA-2 (islet cell antigen 2) as compared to normal lung cells. IA-2, through its effect on dense core vesicles (DCVs), is known to be involved in the secretion of hormones and neurotransmitters. It is believed that the dysregulated release of the neurotransmitter Acetylcholine (ACh) by DCVs has an autocrine effect on SCLC cell growth. Recently, we found that IA-2 is a target of the microRNA miR-342 and that miR-342 mimics suppress the expression of IA-2. The present experiments were initiated to see whether IA-2 and/or miR-342 affect the growth of SCLC. METHODS: SCLC cell growth was evaluated following the knockdown of endogenous IA-2 with RNAi or by overexpressing miR-342 with a mimic. The secretion and content of ACh in SCLC cells was analyzed using a human acetylcholine ELISA (enzyme-linked immunosorbent assay) kit. RESULTS: The knockdown of endogenous IA-2 by RNAi reduced SCLC cell growth within 4 days by 40 % or more. Similar results were obtained when these cell lines were transfected with a miR-342 mimic. The knockdown of IA-2 by RNAi or miR-342 with a mimic also resulted in a significant decrease in the secretion of ACh, one of the autocrine hormones secreted by SCLC. Further studies revealed that the growth of SCLC cell lines that had been treated with the miR-342 mimic was restored to nearly normal levels by treatment with ACh. CONCLUSION: Our studies show for the first time that both miR-342 and its target gene IA-2 are involved in the growth process of SCLC cells and act by their effect on autocrine secretion. These findings point to possible new therapeutic approaches for the treatment of autocrine-induced tumor proliferation. PMID- 27670445 TI - Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer. AB - BACKGROUND: Indonesian mistletoe grows on various trees. Mango Mistletoes (Dendrophthoe pentandra) is one type of mistletoe that grown on mango tree (.benalu mangga in bahasa Indonesia). Our study used mistletoe as a parasitic plant that has been used for traditional medicine. It has been known that Dendrophtoe pentandra extract (DPE) anti-inflammatory and anticancer. Furthermore, it is necessary to follow-up study in vivo to evaluate the response to treatment of new cancer therapeutic agents. This research aimed to determine the levels of IL-22, myeloperoxide (MPO), proliferation and wild-type p53 expression after the administration of DPE to murine models of CAC. METHODS: Mouse colitis associated colon cancer (CAC) was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol, each cycle consisted of seven days of 5 % DSS in the drinking water and followed by seven days of regular water. This study consists of five treatment groups: I was treated water only (control), II was administrated by (DSS only, without DPE), (III-V) were administrated by DPE (125 mg/kg BW, 250 mg/kg BW and 500 mg/kg BW) respectively. The administrated of DPE were started from the 8th weeks, were continued until 21 weeks. At the end of 21 weeks of the experiment, mice were sacrificed, colon tissue was removed, and then subjected to ELISA, flow cytometry, real-time PCR and histology examination. RESULTS: Administration of DPE 250 mg/kgBW significantly reduce the levels of IL 22 and MPO compared with DSS only group (p < 0.001; p < 0.001). Colonic epithelial cells proliferation of group IV (DPE 250 mg/kgBW) were significantly lower than III and V groups. There was no significant change in the S phase in mice were treated DPE 125 mg/kg BW and 500 mg/kg BW, while administration of DPE 250 mg/kg BW was able to increase the percentage of cells in S phase. The expression of mRNA p53 was up regulated in mice received DPE 125 mg/kg BW. CONCLUSION: These findings indicate that the DPE could inhibit colonic epithelial cells proliferation through p53 pathway independently. This study also showed that DPE could be potential sources of new therapy. PMID- 27670447 TI - Aromatherapy: the essentials. AB - The aim of this Learning Unit is to raise your knowledge and professional awareness of the issues involved in the training and practice of aromatherapy and its applicability to nursing practice. This unit is not a substitute for professional training, but it is hoped that from the knowledge gained, more nurses may go on to investigate further and train in aromatherapy and other complementary therapies to enhance patient care. PMID- 27670446 TI - Influenza and pneumococcal vaccination in Australian adults: a systematic review of coverage and factors associated with uptake. AB - BACKGROUND: In the absence of an adult vaccination register, coverage estimates for influenza and pneumococcal vaccination come from surveys and other data sources. METHODS: Systematic review and meta-analysis of studies examining vaccination coverage in Australian adults from 1990 to 2015, focusing on groups funded under the National Immunisation Program, and intervals prior to and following the introduction of universal funding. RESULTS: Twenty-two studies met the inclusion criteria; 18 used self-report to determine vaccination status. There were 130 unique estimates of coverage extracted. Among adults aged >=65y, during the period of universal funding (1999-onwards), the summary estimate of annual influenza vaccination coverage from 27 point estimates was 74.8 % (95 % CI 73.4-76.2 %; range 63.9-82.4 %); prior to this period (1992-1998) from 10 point estimates it was 61.3 % (95 % CI 58.0-64.6 %; range 44.3-71.3 %). For the period of universal funding for pneumococcal vaccination (2005-onwards) the summary estimate for coverage was 56.0 % (95 % CI 53.2-58.8 %; range 51.2-72.8 %, 10 point estimates); prior to 2005 it was 35.4 % (95 % CI 18.8-52.0 %; range 15.4 45.2 %). Coverage for both vaccines was significantly higher following the introduction of universal funding. Influenza vaccination coverage in those aged 18-65 years with a medical indication was lower but data were not combined. Seven studies reported on Aboriginal Australians with three studies reporting five coverage estimates for influenza vaccination in adults >=65 years (range 71 % - 89 %). CONCLUSIONS: Adult influenza and pneumococcal vaccination coverage has increased since the introduction of universal funding, but remains sub-optimal, with pneumococcal coverage lower than influenza. IMPLICATIONS: This review highlights the need for more coverage data overall and in high risk groups, to support public health programs to improve coverage. PMID- 27670448 TI - Editorial. AB - People understand hospitals. If a hospital needs an item of technological wizardry, local people will go to extraordinary lengths to raise funds. If an old person at home needs regular qualified nursing care, will anyone sit in a bath of cold custard for a day to raise cash to provide this essential resource? At a more sophisticated level, there are endless examples of shroud-waving hospital consultants whose decision to go public to draw attention to a lack of resources has been followed by public sympathy and action to remedy the situation. PMID- 27670449 TI - Bassetlaw deaths investigation is widened. AB - Police have widened an investigation into the deaths of two patients at a Nottinghamshire Hospital to include eight other hospitals and over 50 suspicious incidents according to newspaper reports list weekend. PMID- 27670450 TI - Cot deaths programme 'set back research'. AB - Professional organisations were swamped with calls from worried members after a television programme claimed cot mattresses were a factor in sudden infant death syndrome. PMID- 27670451 TI - Community care faces crisis. AB - Nursing unions have called on the government to intervene after counties across England said they were on the brink of running out of money to fund community care. PMID- 27670453 TI - MPs urged to keep nurses' seat on purchasing body. AB - MPs were being urged to support the principle of a nurse executive on every new purchasing body in advance of this week's Commons debate on the health measures outlined in the Queen's Speech. PMID- 27670452 TI - Critic of staff levels suspended by trust. AB - A health visitor has been suspended by a London trust because she repeatedly raised concerns about staffing levels, the Health Visitors' Association claimed last week. PMID- 27670454 TI - Edinburgh to get L140m hospital. AB - Plans to close four Edinburgh hospitals and build a L140 million new Royal Infirmary for the city have been approved by the Scottish Office. PMID- 27670455 TI - Glasgow hospital announces 50 redundancies. AB - Receivers managing the troubled Health Care International announced almost 50 redundancies last week, but only two of the nurses at the controversial private hospital were included. PMID- 27670456 TI - Sickness through stress could lead to compensation. AB - Nurses who become ill because of stress at work could be helped by a social worker's High Court victory, the Royal College of Nursing has said. PMID- 27670457 TI - Cancer centre faces job cuts after overspend. AB - A leading cancer treatment centre is calling for voluntary redundancies to help ease I a L650,000 overspend on its drugs budget. PMID- 27670458 TI - ? AB - Heaven must wait: Two-year-old Heaven de Jesus is to be featured in a TV documentary on Pittsburgh's pioneering transplant centre which will be shown next month. Heaven, pictured with her father Luis, is one of 33,000 people waiting for the life-saving operation in America. First Tuesday: Miracle Workers will be shown at 10pm on Tuesday 6 December on ITV channels. PMID- 27670459 TI - Big fall in deaths predicted. AB - More than 750,000 lives could be saved in the UK over the next 25 years through changes in lifestyle, new medicines and new biomedical technologies, according to a recent study carried out by the Office of Health Economics. PMID- 27670461 TI - Tribute to nurses but still no pay rise. AB - Health secretary Virginia Bot- tomley paid tribute to the nation's nurses last week, sparking calls from unions for her to match her words by boosting nurses' pay. PMID- 27670462 TI - Minister attacks jargon. AB - Yet another threat to the National Health Service has been revealed - watch out, there's an acronym about. PMID- 27670463 TI - New obstetric unit not being used. AB - Pregnant women are being denied use of a brand new L1.5 million obstetric unit, partly because elderly patients need the beds, says a Labour MP. PMID- 27670464 TI - Gender sensitivity needed in A&E. AB - A&E nurses should be more gender sensitive when asking patients questions about whom to contact in the event of an accident, the RCN A&E Association annual conference in Daresbury has been told. PMID- 27670467 TI - Easy-to-measure advantage. AB - Measuring clinical outcomes can give an unfair advantage to services which are easy to measure, a nurse academic has warned. PMID- 27670466 TI - ? AB - Team nursing: Nursing students from the University of Greenwich have been presented with the Duke of Edinburgh's Award after competing against 40 other teams in The Great Escape activity day at Eastnor Castle in Hertfordshire. The six, who met for the first time on the day, had to complete a range of activities, including orienteering, assault boat racing, abseiling, clay pigeon shooting, quizzes and an egg race. They are, left to right, back: Emma Starmer Smith, Sheila Cousins, Julie McKenzie. Front: Greg Watson, Mark Bottomley and Tony Convery. PMID- 27670468 TI - Outcome-based contracts initiative. AB - District nurses in east London have helped draw up a contract with a health authority based on how many patients they think they will cure. PMID- 27670470 TI - Health service money is 'wasted on nurses'. AB - Nurses in Wales have hit out against claims they should sacrifice their jobs to improve patient care. PMID- 27670469 TI - New rules from HSE. AB - New health and safety at work regulations to protect women who are pregnant, new mothers and those who arc breastfeeding, are due to come into effect on 1 December. PMID- 27670471 TI - American nurses report safety risk to patients. AB - American nurses are reporting deteriorating levels of patient care and openly expressing concern about patient safety, the American Nurses' Association has claimed. PMID- 27670472 TI - Parents not fully involved in care of children in hospital. AB - Parental participation in the care of sick children in hospital is often limited to basic 'mothering work', with parents often unsure as to what is expected of them, delegates at the recent paediatric nursing conference heard. PMID- 27670473 TI - Teachers need guidelines to give drugs safely. AB - Teachers who have to give children medicines at school need national guidelines, a report in the Drug and Therapeutics Bulletin has argued. PMID- 27670475 TI - Risk factors in acute epiglottitis. AB - Most adults who have acute epiglottitis can be managed conservatively and have low morbidity and mortality, American researchers report. PMID- 27670474 TI - Hyponatraemia and transcervical surgery. AB - Absorption of more than a litre of of irrigating fluid during transcervical surgery is associated with cerebral oedema and nausea, secondary to dilutional hyponatraemia, researchers from Denmark report. PMID- 27670476 TI - Determining early pregnancy in A&E. AB - As many as 6 per cent of women attending accident and emergency departments might be pregnant but not realise the fact, American researchers report. PMID- 27670478 TI - Still a long way to go. AB - Support for women's employment issues among top managers is growing, according to the latest update from the government's project to bring equality to the workforce. PMID- 27670477 TI - Ethnic minority women keen to have smears. AB - Women from ethnic minority groups are enthusiastic about cervical cytology once they understand the purpose of the screening and call recall system. PMID- 27670479 TI - Sensationalist or blaming the messenger? AB - The announcement of a 'fundamental review' of the workings of the UK Central Council in the aftermath of registrar Colin Ralph's departure prompted immediate calls from nursing unions for the UKCC to become more open and accountable. PMID- 27670480 TI - More financial training needed. AB - Welsh nurses charged with managing ward budgets need much more training for the task, a new report has revealed. PMID- 27670481 TI - On your lobby horse. AB - From Des Lynam to district nurses and from Alan Partridge to practice nurses, support for the Right to Nurse campaign keeps on coming. The list of signatories to the Right to Nurse Contract is growing all the time and many of you have written or phoned with your experiences of nursing in the Nineties. But we still want more. If you haven't signed the Contract yet, please do so and encourage your chief executive to do so too. And if you feel your right to nurse is being restricted by inadequate resources, too few staff, or for any other reason, please let us know. This week, we take a break from looking at the clauses of the Right to Nurse Contract and feature an article by Kathleen Weekes, chief nursing consultant at the Employment Service. PMID- 27670482 TI - Statistically speaking... AB - The fact that nearly half the nurses who responded to a Nursing Standard survey earlier this year were looking for a new job may come as no surprise to those of you who live with the dissatisfaction and low morale which seem to characterise much of nursing today. PMID- 27670483 TI - Understanding the nature of sleep. AB - This is the first article in a series of three looking at patients' sleep in hospitals. This article explores the nature of sleep and reviews the various theories that have been put forward to explain why we need to sleep. The other two articles will concentrate on sleep disorders and hospitalisation, and the mle of the night nurse. PMID- 27670484 TI - Child abuse and the legal system Wattam Ianigmans Making a case in child protection 208pp L11.95 0-582-09281-7. AB - Quite simply Corinne Warrant has written one of the best texts I have ever read on child protection. Her book is based on ethnographic research carried out within both a child protection team and the Crown Prosecution Service, and explores the processes through which children become court witnesses to abuse that they themselves have received. PMID- 27670485 TI - Nurse researcher Nurse researcher Editor Mathieson Alex Scutari Press 96pp four times yearly L16 subscription 1-873853-16-5. AB - 'Of all research methods, observation is perhaps the closest to everyday life,' argues Maureen Swanwick in the latest issue of Nurse Researcher. PMID- 27670487 TI - New this month. PMID- 27670486 TI - ? AB - The International Nursing Review reports on an electronic journal giving nurses access to latest research findings. The Online Journal of Knowledge Synthesis for Nursing apparently needs a personal computer with Windows software and a communications network hookup such as Internet, or a modem. Details from the publisher, Sigma Theta Tau, 550 West North Street, Indianapolis, IN 46202, USA. PMID- 27670490 TI - Resources for nursing research: an annotated bibliography Resources for nursing research: an annotated bibliography Second edition Clamp Cynthia et al Library Association Publishing 458pp L45 1-85604-117-4. AB - How do you take the first step in identifying literature related to nursing research? The answer could be in Resources for Nursing Research. PMID- 27670489 TI - Ethics: education and research Ethics: education and research Tschudin Verena Editor Scutari Press 152pp L12.99 1-873853-1 1-4. AB - : Research can be an ethical minefield, particularly where it involves patients' interests, and especially when it involves commercial sponsorship. ETHICS: Education and Research is the latest in Scutari's series of specifically targeted books exploring ethical issues which are relevant to practising nurses and P2000 students. PMID- 27670491 TI - Ann Bradshaw Scutari Press 362pp L19.99 1-873853-06-8. AB - Lighting the Lamp: The Spiritual Dimension of Nursing Care Spirituality plays a major, if ill-defined, role in the motivation to deliver high quality professional nursing care, yet the subject is hardly recognised and rarely discussed. The results of years of research, Lighting the Lamp: The Spiritual Dimension of Nursing Care discusses the history and theology of spirituality and guides the reader through the myths and misconceptions surrounding the subject, demonstrating how current practice can benefit from the practical application of spiritual concepts. PMID- 27670492 TI - New this month. PMID- 27670493 TI - Rosie Higgins Daniels Publishing. 38 Cambridge Place, Cambridge CB2 INS. Tel: 0223 467144. Fax: 0223 467145.24 slides, 50pp of lecture notes in a freestanding folder, glossary of terms and definitions. L60 including postage and packing 0 9517228-7-5. AB - Knowing the Score. A Drug Awareness Slide Set and Teaching Guide. PMID- 27670495 TI - Multimedia offers an overview of recent publications and resources with an invaluable star rating guide Robert M Youngson Multimedia offers an overview of recent publications and resources with an invaluable star rating guide Harper collins 284pp L4.99 0-00-470535-1 [Formula: see text]. AB - Collins Pocket Reference Prescription Drugs: A Guide to Prescription Drugs and Their Uses. PMID- 27670496 TI - New this month. AB - ? Strategies for Interpreting Qualitative Data Martha S Feldman SAGE Publications 72pp L7.50 ISBN 0-8039-5916-8. PMID- 27670497 TI - Learning disabilities. AB - The West Cheshire NHS Trust has produced a video entitled Valued Lives. Presented in two parts, it aims to. PMID- 27670499 TI - Lost for words? AB - Rhone-Poulenc Rorer has sponsored the publication of a new booklet from the British Association of Cancer United Patients (BACUP) entitled Lost for Words: l low to Talk to Someone with Cancer. PMID- 27670498 TI - New home for Graves. AB - Graves Medical Audiovisual library is now based with Concord Video and Film Council Ltd, 201 Felixstowe Road, Ipswich, Suffolk 1P3 9BJ. Tel: 0473 726012/715754. Fax: 0473 274531. A registered charity, Concord claims that it is possibly the largest educational video and film library in the UK. PMID- 27670500 TI - Video health channel. AB - Leicestershire Health has just launched a video health channel in a bid to ensure that vital health messages are reaching target audiences. Twenty GP practices are taking part in the two-year pilot scheme which consists of a specially produced 20-minute video played continually on a TV screen in the surgery waiting room. It is estimated that about 125,000 will have access to the Health Channel. Further information from Ted Longwith, associate director, primary care, Leicestershire Health on 0533 588972. PMID- 27670501 TI - Deaf directory. AB - The third edition of the 199415 Directory from the Council for the Advancement of Communication with Deaf People (CACDP) is now available. Information on 192 sign language interpreters, lipspeakers, interpreters for deafblind people and speech to text reporters is provided. Details from CACDP on 0191 374 3607. PMID- 27670502 TI - Free videos. AB - CFL Vision has produced a new catalogue of nursing videos which can be borrowed free of charge for a five-day period. The company runs a helpline on 019.37 541010, with experienced staff to help search for the right programme from its library of around 500 titles. PMID- 27670503 TI - Tony shows you how. AB - The secret of successful presentations can be yours, according to BBC for Business which has produced a training video package starring Tony Slattery titled Speak for Yourself. PMID- 27670504 TI - Listen and learn. AB - A new health pack of audio tape programmes for practice libraries is now available. The Health Audio Pack aims to enable nurses and doctors to offer simple self-help management programmes to patients who have chronic health problems such as depression, asthma and back pain. The set of eight costs L61.60, inclusive of VAT, post and packing, from WLAP Ltd, PO Box 1, Wirral L47 7DD. For more information call 051-632 0662. PMID- 27670505 TI - We do bother to educate our nurses. AB - I write to refute the statements made by your correspondent who wrote the letter 'Bad deal for nurses in private sector' (November 2). PMID- 27670506 TI - Nurses are more than up to the task. AB - Why is there so much agonising over nurses undertaking some of the work previously seen as the responsibility of junior doctors, when in reality it has been senior nurses who have taught junior doctors how to perform these tasks (Nurses forced to take on more work, News, November 2)? PMID- 27670507 TI - The system's painful sense of urgency. AB - It was with sadness and disgust that I read of the plight of Sean Kelly and his family (System failure, Viewpoint, November 9). PMID- 27670508 TI - Another invisible casualty of nursing. AB - I can relate very strongly to Roger Cowell's article, 'Backs to the wall' (Viewpoint, November 9). PMID- 27670509 TI - Left in the lurch by continuous testing. AB - I was interested in Julia Hopewell's letter regarding state finals versus continuous assessment (Continuous assessment fairest, Letters, November 2). PMID- 27670510 TI - Information exchange. AB - * I work on a paediatric unit where we are implementing team nursing. We are also going to update our philosophy of care and I would be interested in any help, advice, guidelines from anyone who has recently carried out work on their own philosophy of care. PMID- 27670511 TI - Prime contendersMaureen Lahiff describes the varied backgrounds of the entrants to the Clinical Practice and Management Awards, a joint initiative between Smith & Nephew Healthcare, the Royal College of Nursing and Nursing Standard. AB - More than 350 nurses entered the 1994 Smith & Nephew Healthcare/ Nursing Standard/Royal College of Nursing Clinical Practice and Management Awards. They came from all over the British Isles - from Stornaway to the Channel Islands, from Northern Ireland to Newcastle, from many points in between and with a sprinkling from the Continent. PMID- 27670512 TI - A golden opportunity. AB - The programme which awaits the 12 winners at Sundridge Park has been changed slightly from last year's. According to programme manager Steve Rath- born, this is an inevitable result of monitoring changes in nursing and management practice, and listening closely to what last year's and this year's winners say. PMID- 27670513 TI - Introducing this year's winners. AB - The judges were extremely impressed by the quality of this year's entrants. The essays showed insight, determination and a clear grasp of the needs of a changing profession. The winners come from a variety of backgrounds and will be able to offer a wealth of experience to the course at Sundridge Park. PMID- 27670514 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodivorth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27670515 TI - Effect of salt reduction on iodine status assessed by 24 hour urinary iodine excretion in children and their families in northern China: a substudy of a cluster randomised controlled trial. AB - OBJECTIVE: To study the effect of salt reduction on iodine status and to determine whether iodine consumption was still adequate after salt reduction in a population where universal salt iodisation is mandatory. DESIGN: A substudy of a cluster randomised controlled trial, with schools randomly assigned to either the intervention or the control group. SETTING: 28 primary schools in Changzhi, northern China. PARTICIPANTS: 279 children in grade 5 of primary school (mean age: 10.1); 553 adults (age: 43.8). INTERVENTION: Children were educated about the harmful effects of salt and how to reduce salt intake using the schools' usual health education lessons. Children then delivered the message to their families. The duration was 1 school term (~3.5 months). MAIN OUTCOME MEASURE: Difference between the intervention and control groups in the change of iodine intake as measured by repeat 24 hour urinary iodine from baseline to the end of the trial. RESULTS: At baseline, the mean salt intake was 7.0+/-2.5 g/day in children and 11.7+/-4.4 g/day in adults and the median iodine intake was 165.1 MUg/day (IQR: 122.6-216.7) and 280.7 MUg/day (IQR: 205.1-380.9) in children and adults, respectively. At the end of the study, salt and iodine decreased in the intervention compared with control group. The mean effect on salt for intervention versus control was -1.9 g/day (95% CI -2.6 to -1.3) in children and 2.9 g/day (95% CI -3.7 to -2.2) in adults. The mean effect on iodine was -19.3% (95% CI -29.4% to -7.7%) in children and -11.4% (95% CI -20.3% to -1.5%) in adults. CONCLUSIONS: With ~25% reduction in salt intake, there was a significant reduction in iodine consumption in northern China where salt is iodised. Despite this, iodine intake was still adequate, and well above the estimated average requirement. Our findings indicate that reducing salt to the WHO's target-30% reduction by 2025-will not compromise iodine status. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01821144. PMID- 27670516 TI - Partnering with consumers to develop and evaluate a Vietnamese Dementia Talking Book to support low health literacy: a qualitative study incorporating codesign and participatory action research. AB - OBJECTIVE: The aim of the Vietnamese Dementia talking-book was to address low health literacy in older people of Vietnamese background living with dementia through the provision of an online resource to help individuals, their families and carers better understand and manage this condition and provide information about available dementia services. DESIGN: This qualitative study used codesign and participatory action research to develop and refine the talking-book in consultation with expert stakeholders, a consumer advocacy group and the Vietnamese community to assess its utility and ensure cultural and linguistic appropriateness and relevance. PARTICIPANTS: 59 members of the Vietnamese community, 11 stakeholders from community health services and ethnic agencies, consumer advocacy groups and the research team participated in the codesign and refinement of the talking-book. 22 members of the Vietnamese community appraised the final product. SETTING: Vietnamese community planned activity groups in the Western, Northern and Southern suburbs of Melbourne, Australia. RESULTS: Our codesign study outlines the process required to develop a Vietnamese Dementia Talking-Book resource partnering with consumers and expert stakeholders to identify consumer need, selection of the content and appropriate language level, construction of the book, measuring acceptability of the talking-book, modification based on feedback and production and dissemination. Feedback on the final version of the talking-book revealed widespread consensus that the book enhanced the knowledge of members of the Vietnamese community in regard to understanding dementia and navigation and accessing of available services. CONCLUSIONS: This free internationally available online Vietnamese Dementia Talking-Book facilitates improved dementia-related health literacy in the Vietnamese community. The book also serves as a tool to facilitate the provision of care to Vietnamese people living with memory loss by assisting health professional staff to develop relationships with Vietnamese clients, their families and carers in a culturally appropriate manner. PMID- 27670517 TI - Maternal-related deaths and impoverishment among adolescent girls in India and Niger: findings from a modelling study. AB - BACKGROUND: High levels of maternal mortality and large associated inequalities exist in low-income and middle-income countries. Adolescent pregnancies remain common, and pregnant adolescent women face elevated risks of maternal mortality and poverty. We examined the distribution across socioeconomic groups of maternal deaths and impoverishment among adolescent girls (15-19 years old) in Niger, which has the highest total fertility rate globally, and India, which has the largest number of maternal deaths. METHODS: In Niger and India, among adolescent girls, we estimated the distribution per income quintile of: the number of maternal deaths; and the impoverishment, measured by calculating the number of cases of catastrophic health expenditure incurred, caused by complicated pregnancies. We also examined the potential impact on maternal deaths and poverty of increasing adolescent girls' level of education by 1 year. We used epidemiological and cost inputs sourced from surveys and the literature. RESULTS: The number of maternal deaths would be larger among the poorer adolescents than among the richer adolescents in Niger and India. Impoverishment would largely incur among the richer adolescents in Niger and among the poorer adolescents in India. Increasing educational attainment of adolescent girls might avert both a large number of maternal deaths and a significant number of cases of catastrophic health expenditure in the 2 countries. CONCLUSIONS: Adolescent pregnancies can lead to large equity gaps and substantial impoverishment in low-income and middle income countries. Increasing female education can reduce such inequalities and provide financial risk protection and poverty alleviation to adolescent girls. PMID- 27670518 TI - Prospective comorbidity-matched study of Parkinson's disease and risk of mortality among women. AB - BACKGROUND: Individuals with Parkinson's disease (PD) may have an increased risk of overall mortality compared to the general population. Women may have lower mortality rates from PD than men; however, studies among women on the effect of PD on mortality have been limited and may not have adequately controlled for confounding by comorbidities. METHODS: We conducted a matched cohort study among participants in the Women's Health Study. 396 incident PD cases were identified through self-report. Each PD case was matched by age to a comparator who was alive and had the same modified Charlson comorbidity score as the PD case. The PD cases and matched comparators were followed for all-cause mortality. Cox proportional hazards models adjusted for age at the index date, smoking, alcohol consumption, exercise and body mass index were used to determine the association between PD and mortality. RESULTS: During a median of 6.2 years of follow-up, 72 women died (47 PD cases and 25 comparators). The multivariable-adjusted HR for mortality was 2.60 (95% CI 1.56 to 4.32). CONCLUSIONS: PD was associated with more than a twofold increased risk of all-cause mortality among women. Results are similar to those observed among men. PMID- 27670519 TI - Effects of added involvement from concerned significant others in internet delivered CBT treatments for problem gambling: study protocol for a randomised controlled trial. AB - INTRODUCTION: Problem gambling is a public health concern affecting ~2.3% of the Swedish population. Problem gambling also severely affects concerned significant others (CSOs). Several studies have investigated the effect of individual treatments based on cognitive-behavioural therapy (CBT), but less is known of the effect of involving CSOs in treatment. This study aims to compare an intervention based on behavioural couples therapy (BCT), involving a CSO, with an individual CBT treatment to determine their relative efficacy. BCT has shown promising results in working with substance abuse, but this is the first time it is used as an intervention for problem gambling. Both interventions will be internet delivered, and participants will receive written support and telephone support. METHODS AND ANALYSIS: A sample of 120 couples will be randomised to either the BCT condition, involving the gambler and the CSO, or the CBT condition, involving the gambler alone. Measures will be conducted weekly and at 3, 6 and 12 months follow-up. The primary outcome measure is gambling behaviour, as measured by Timeline Followback for Gambling. This article describes the outline of the research methods, interventions and outcome measures used to evaluate gambling behaviour, mechanisms of change and relationship satisfaction. This study will be the first study on BCT for problem gambling. ETHICS AND DISSEMINATION: This study has been given ethical approval from the regional ethics board of Stockholm, Sweden. It will add to the body of knowledge as to how to treat problem gambling and how to involve CSOs in treatment. The findings of this study will be published in peer-reviewed journals and published at international and national conferences. TRIAL REGISTRATION NUMBER: NCT02543372; Pre-results. PMID- 27670520 TI - Burden assessment of podoconiosis in Wayu Tuka woreda, east Wollega zone, western Ethiopia: a community-based cross-sectional study. AB - OBJECTIVE: Podoconiosis is a neglected tropical disease characterised by a slowly progressive swelling of the foot and lower leg. It is prevalent among subsistence barefoot farmers who live and work in highland areas of the tropics. This study was conducted in Wayu Tuka 'woreda' (district), western Ethiopia to determine the prevalence of podoconiosis and assess factors associated with acute adenolymphangitis (ALA) episodes. METHODS AND ANALYSIS: A two phase, community based cross-sectional study was conducted between January and March 2015. First, all households in the district were surveyed to determine the prevalence of podoconiosis. This was followed by a second phase in which 366 people with podoconiosis from four randomly selected 'kebeles' (subdistricts) were assessed for clinical features of the disease, shoe-wearing habits, personal hygiene, social stigma and functional impairment. Data entered into Epi DATA were then exported to SPSS. Logistic regression analysis was conducted to identify factors associated with ALA. RESULTS: Prevalence of podoconiosis in the population was 3.05% (1197/39 256) (95% CI 2.9% to 3.2%). The prevalence was significantly higher among women than men (3.67% vs 2.4%). Most (92.2%) people with podoconiosis were in the economically active age group (15-64 years) in the first phase survey. Of participants in the second phase of the study, 43% had stage 2 disease and 38.1% had 'moss'-like skin changes. On average, people with podoconiosis had 23.3 episodes of ALA/year and each person with podoconiosis lost 149.5 days of activity/year. Never walking barefoot and daily foot washing were both associated with decreased odds of ALA (AOR=0.23; 95% CI 0.06 to 0.80 and 0.09; 95% CI 0.01 to 0.75, respectively). CONCLUSIONS: A relatively high prevalence of podoconiosis, frequent ALA episodes and considerable decreases in daily activities were identified in this district. Footwear use and daily foot hygiene were associated with decreased odds of ALA. We recommend prevention and morbidity management interventions to address this developmental challenge. PMID- 27670521 TI - Cost-effectiveness modelling of telehealth for patients with raised cardiovascular disease risk: evidence from a cohort simulation conducted alongside the Healthlines randomised controlled trial. AB - OBJECTIVES: To investigate the long-term cost-effectiveness (measured as the ratio of incremental NHS cost to incremental quality-adjusted life years) of a telehealth intervention for patients with raised cardiovascular disease (CVD) risk. DESIGN: A cohort simulation model developed as part of the economic evaluation conducted alongside the Healthlines randomised controlled trial. SETTING: Patients recruited through primary care, and intervention delivered via telehealth service. PARTICIPANTS: Participants with a 10-year CVD risk >=20%, as measured by the QRISK2 algorithm, and with at least 1 modifiable risk factor, individually randomised from 42 general practices in England. INTERVENTION: A telehealth service delivered over a 12-month period. The intervention involved a series of responsive, theory-led encounters between patients and trained health information advisors who provided access to information resources and supported medication adherence and coordination of care. PRIMARY AND SECONDARY OUTCOME MEASURES: Cost-effectiveness measured by net monetary benefit over the simulated lifetime of trial participants from a UK National Health Service perspective. RESULTS: The probability that the intervention was cost-effective depended on the duration of the effect of the intervention. The intervention was cost-effective with high probability if effects persisted over the lifetime of intervention recipients. The probability of cost-effectiveness was lower for shorter durations of effect. CONCLUSIONS: The intervention was likely to be cost-effective under a lifetime perspective. TRIAL REGISTRATION NUMBER: ISRCTN27508731; Results. PMID- 27670522 TI - Data sharing through an NIH central database repository: a cross-sectional survey of BioLINCC users. AB - OBJECTIVE: To characterise experiences using clinical research data shared through the National Institutes of Health (NIH)'s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) clinical research data repository, along with data recipients' perceptions of the value, importance and challenges with using BioLINCC data. DESIGN AND SETTING: Cross-sectional web based survey. PARTICIPANTS: All investigators who requested and received access to clinical research data from BioLINCC between 2007 and 2014. MAIN OUTCOME MEASURES: Reasons for BioLINCC data request, research project plans, interactions with original study investigators, BioLINCC experience and other project details. RESULTS: There were 536 investigators who requested and received access to clinical research data from BioLINCC between 2007 and 2014. Of 441 potential respondents, 195 completed the survey (response rate=44%); 89% (n=174) requested data for an independent study, 17% (n=33) for pilot/preliminary analysis. Commonly cited reasons for requesting data through BioLINCC were feasibility of collecting data of similar size and scope (n=122) and insufficient financial resources for primary data collection (n=76). For 95% of respondents (n=186), a primary research objective was to complete new research, as opposed to replicate prior analyses. Prior to requesting data from BioLINCC, 18% (n=36) of respondents had contacted the original study investigators to obtain data, whereas 24% (n=47) had done so to request collaboration. Nearly all (n=176; 90%) respondents found the data to be suitable for their proposed project; among those who found the data unsuitable (n=19; 10%), cited reasons were data too complicated to use (n=5) and data poorly organised (n=5). Half (n=98) of respondents had completed their proposed projects, of which 67% (n=66) have been published. CONCLUSIONS: Investigators were primarily using clinical research data from BioLINCC for independent research, making use of data that would otherwise have not been feasible to collect. PMID- 27670523 TI - Knowledge, beliefs and attitudes of Muslim footballers towards Ramadan fasting during the London 2012 Olympics: a cross-sectional study. AB - OBJECTIVES: Muslims observe fasting during the month of Ramadan by abstaining from eating and drinking from dawn to sunset. Available literature shows that although several studies have been conducted on athletes to determine the effects of Ramadan fasting in terms of physical fitness and performance, little data are available regarding the knowledge, beliefs and attitudes of athletes (particularly footballers) towards Ramadan fasting during high-level competitions. This study explored the knowledge, beliefs and attitudes towards Ramadan fasting among football players participating in the London 2012 Olympics football tournament. DESIGN: Cross-sectional study. SETTINGS: Team training facility. PARTICIPANTS: 54 Muslim footballers participating in the London Olympics, 2012 OUTCOME MEASURES: Each participant was asked to complete a pre validated structured questionnaire to assess knowledge, beliefs and attitudes regarding Ramadan fasting and their intention to fast during London 2012. RESULTS: Of the 54 participating athletes, 21(39%) reported that they intended to fast during Ramadan, but not on a match day. This attitude differed across three teams interviewed -83%, 15% and 0%-showing cross-cultural variation. Overall, there was a lack of knowledge among footballers regarding the effects of Ramadan fasting on sleep and performance; around 30% of athletes gave incorrect responses. This knowledge was independent of their decision to fast on non competition days (p>0.05). CONCLUSIONS: This is the first study to describe the knowledge, beliefs and attitudes towards Ramadan fasting among athletes from Muslim-majority countries participating in a high-level competition. Appropriate knowledge can ensure optimum performance for athletes during Ramadan fasting. Coaches, family members and friends also in possession of this knowledge can provide moral support to the players. PMID- 27670524 TI - Is tuberculosis health education reaching the public in China? A cross-sectional survey in Guizhou Province. AB - BACKGROUND: Knowledge about tuberculosis (TB) is important for TB control, and China's national TB control guidelines emphasise TB health promotion. A 2010 national TB epidemiology survey showed that the general public had limited knowledge and awareness of TB. OBJECTIVE: To assess the level of TB knowledge after 5 years of TB health promotion in Guizhou Province, one of the regions with the highest TB burden in China. DESIGN AND SETTING: A community-based, cross sectional survey of 10 237 residents of Guizhou Province from June to August 2015. Multiple logistic regression models were used to examine factors associated with core TB knowledge and TB health education among respondents. RESULTS: Overall, residents of Guizhou Province had inadequate knowledge of TB. The overall awareness of TB was 41.5%. Less than 30% of respondents were familiar with China's policy of free treatment for TB or knew that the disease could be cured. Factors associated with core TB knowledge included gender, age, ethnicity, education, occupation, region, and having received TB health education. Women, older adults, people employed in non-government institutions, and those living in counties with low TB burdens had little access to TB health education, whereas people with higher education levels had greater access. Respondents' sources of TB knowledge did not necessarily match their preferred channels for delivery of TB health education. CONCLUSIONS: Our findings indicate that TB health education should be further strengthened in China and other countries with a high TB burden. TB health education programmes require further formative and implementation research in order to improve programme effectiveness. PMID- 27670525 TI - Multi-pass microscopy. AB - Microscopy of biological specimens often requires low light levels to avoid damage. This yields images impaired by shot noise. An improved measurement accuracy at the Heisenberg limit can be achieved exploiting quantum correlations. If sample damage is the limiting resource, an equivalent limit can be reached by passing photons through a specimen multiple times sequentially. Here we use self imaging cavities and employ a temporal post-selection scheme to present full field multi-pass polarization and transmission micrographs with variance reductions of 4.4+/-0.8 dB (11.6+/-0.8 dB in a lossless setup) and 4.8+/-0.8 dB, respectively, compared with the single-pass shot-noise limit. If the accuracy is limited by the number of detected probe particles, our measurements show a variance reduction of 25.9+/-0.9 dB. The contrast enhancement capabilities in imaging and in diffraction studies are demonstrated with nanostructured samples and with embryonic kidney 293T cells. This approach to Heisenberg-limited microscopy does not rely on quantum state engineering. PMID- 27670526 TI - Hypermethylated APC in serous carcinoma based on a meta-analysis of ovarian cancer. AB - BACKGROUND: The reduced expression of the Adenomatous polyposis coli (APC) gene, a tumor suppressor gene, through promoter hypermethylation has been reported to play a key role in the carcinogenesis. However, the correlation between APC promoter hypermethylation and ovarian cancer (OC) remains to be clarified. METHODS: A comprehensive literature search was carried out in related research databases. The overall odds ratio (OR) and corresponding 95 % confidence interval (CI) were used to evaluate the effects of APC promoter hypermethylation on OC and clinicopathological characteristics. RESULTS: Ultimately, 12 eligible studies were used in our study, including 806 OC samples, 429 normal controls, 109 benign lesions and 75 LMP samples. The pooled OR showed that APC promoter hypermethylation was significantly higher in OC than in normal and benign controls (OR = 6.18 and OR = 3.26, respectively). No significant correlation was observed between OC and low malignant potential (LMP) tumors (P = 0.436). In the comparison of OC and normal controls, subgroup analysis based on race showed that the overall OR of APC promoter hypermethylation was significant and similar in Asians and Caucasians (OR = 8.34 and OR = 5.39, respectively). A subgroup analysis based on sample type found that the pooled OR was significantly higher in blood than in tissue (OR = 18.71 and OR = 5.74, respectively). A significant association was not observed between APC promoter hypermethylation and tumor grade or tumor stage. The pooled OR indicated that APC promoter hypermethylation was significantly lower in serous carcinoma than in non-serous carcinoma (OR = 0.56, P = 0.02). No obvious publication bias was detected by Egger's test (all P > 0.05). CONCLUSIONS: APC promoter hypermethylation may be linked to the increased risk of OC. It was associated with histological type, but not with tumor grade or tumor stage. Moreover, hypermethylated APC may be a noninvasive biomarker using blood samples. Future studies are required to validate these results. PMID- 27670528 TI - Caudal Duplication: Management of a Rare Congenital Condition. PMID- 27670529 TI - The Utility of Abdominal CT for Preoperative Planning of Percutaneous Endoscopic Gastrostomy Tube Placement. PMID- 27670530 TI - Benign Pneumatosis Intestinalis: Can We Avoid the Knife? PMID- 27670531 TI - A Novel Technique Using Intraoperative Fluoroscopy as a Tool to Achieve Negative Margins for Wire-Guided Partial Mastectomies. PMID- 27670532 TI - Retrograde Intussusception after Roux-en-Y Gastric Bypass. PMID- 27670533 TI - Congenital Symmastia: A Reconstruction Technique. PMID- 27670534 TI - Impact of Health-Care Worker Attitudes Toward Organ Donation. PMID- 27670535 TI - Extralobar Pulmonary Sequestration with Accompanying Ipsilateral Diaphragmatic Eventration. PMID- 27670536 TI - Association between Blood Transfusion, Transfusion Setting, and the Risk of Venous Thromboembolism in Patients with Isolated Orthopedic Trauma. PMID- 27670537 TI - Tracheocarotid Fistula. PMID- 27670538 TI - Management of a Persistent Surgical Scalp Wound Complicated by Folliculitis and Dehiscence. PMID- 27670539 TI - Alcohol, Injuries, and Outcomes Comparing Injured Moped and Motorcycle Drivers. PMID- 27670540 TI - Hyperthyroidism and Thyroid Carcinoma. PMID- 27670541 TI - Laparoscopic-Assisted Endoscopic Retrograde Cholangiopancreaticography after Roux en-Y Gastric Bypass. PMID- 27670542 TI - A Rare Cause of Bowel Obstruction: An Incarcerated Obturator Hernia. PMID- 27670543 TI - Feasibility and Safety of Irreversible Electroporation in Locally Advanced Pelvic and Retroperitoneal Tumors. PMID- 27670544 TI - Association of Duration of Symptoms and Secondary Signs in Ultrasound for Pediatric Appendicitis. PMID- 27670545 TI - Mucoepidermoid Carcinoma of the Lingual Tonsil. PMID- 27670546 TI - Hiatal Hernia Cruroplasty with a Running Barbed Suture Compared to Interrupted Suture Repair. PMID- 27670547 TI - Recurrent Cervical Cancer Presenting as Inflammatory Breast Cancer. PMID- 27670548 TI - Analysis of Endoscopic Retrograde Cholangiopancreatography in Rural Appalachia. PMID- 27670549 TI - A Violation of Occam's Razor: Acute Appendicitis after Motor Vehicle Collision. PMID- 27670551 TI - Unicentric Castleman's Disease Masquerading as a Carcinoid Tumor of the Small Intestine. PMID- 27670550 TI - Concomitant Laparoscopic Ileocolectomy and Ladd's Procedure for Crohn's Ileocolitis with Mesenteric Abscess and Congenital Megacolon. PMID- 27670552 TI - Penetrating Spinal Cord Trauma: A Unique Patient Presentation. PMID- 27670553 TI - Necrotizing Fasciitis in a Healthy Pediatric Patient Caused by Enterobacter cloacae and Serratia marcescens: A Discussion of Diagnosis and Management. PMID- 27670554 TI - Fetus in Fetu-A Case Report with a Variant Host Anastomosis. AB - Fetus in fetu is a rare congenital condition where a vertebrate fetus is found within the body of its host twin. It features a monozygotic parasitic twin attached via a vascular anastomosis to its host circulation. This report describes an instance of fetus in fetu with a variant presentation of its vascular pedicle to its host via the inferior epigastric vasculature. PMID- 27670555 TI - Pediatric Secondary Overtriage in a Statewide Trauma System. AB - Secondary overtriage is a term that describes patients who are discharged home shortly after being transferred, an indication that transfer and hospitalization were unnecessary. The study goal was to identify factors associated with secondary triage. A statewide trauma registry was used to identify trauma patients aged less than 18 years during a 6-year period (2007-2012) who were discharged within 48 hours from arrival and did not undergo a surgical procedure. We compared those that were treated at initial facility and those transferred to a second facility using clinical indices including patterns of injury pattern using multivariate logistic regression. Of the 4441 patients who fit our inclusion criteria, 801 (18%) were transferred. Younger age groups were more likely to be transferred. Factors associated with being transferred included head, spinal, and facial injuries, and patient arrival during the nighttime work shifts. In conclusion, young patients who have signs of possible neurological or spinal injuries and those who arrive during nondaytime shifts during the workday are more likely to be transferred to another trauma center. These may reflect the comfort level and resources of the local facility. PMID- 27670556 TI - Management of Patients with Gastroschisis Requiring Extracorporeal Membrane Oxygenation for Concurrent Respiratory Failure. AB - Treatment of gastroschisis often requires multiple surgical procedures to re establish abdominal domain, reduce abdominal contents, and eventually close the abdominal wall. In patients who have concomitant respiratory failure requiring extracorporeal membrane oxygenation (ECMO), this process becomes further complicated. This situation is rare and only five such cases have been reported in the ECMO registry database. Management of three of the five patients along with results and implications for future care of similar patients is discussed here. Two patients had respiratory failure due to meconium aspiration syndrome and one patient had persistent acidosis as well as worsening pulmonary hypertension leading to the decision of ECMO. The abdominal contents were placed in a spring-loaded silastic silo while on ECMO and primary closure was performed three to six days after the decannulation. All three patients survived and are developmentally appropriate. We recommend avoiding aggressively reducing the abdominal contents and using a silo to conservatively reducing the gastroschisis while the patient is on ECMO therapy. Keeping the intra-abdominal pressure below 20 mm Hg can possibly reduce ECMO days and ventilator time and has been shown to decrease morbidity and mortality. Patients with gastroschisis and respiratory failure requiring ECMO can have good outcomes despite the complexity of required care. PMID- 27670557 TI - Laparoscopic Resection of a Congenital Solitary Hepatic Cyst in an Infant. PMID- 27670558 TI - Preduodenal Portal Vein: A Rare Cause of Neonatal Bowel Obstruction. PMID- 27670559 TI - Paratubal Cyst Torsion with Compromise of the Fallopian Tube in an Adolescent Girl. PMID- 27670560 TI - A Rare Diagnosis for Persistent, Unexplained Fevers and Abdominal Pain in the Pediatric Population. PMID- 27670561 TI - Complications Associated with Bar Fixation after Nuss Repair for Pectus Excavatum. PMID- 27670562 TI - Chylous Ascites in a Neonate with Hydrops Fetalis. PMID- 27670563 TI - Repair of Pectus Excavatum in an Adult: An Example of Disease Progression. PMID- 27670564 TI - Venovenous Extracorporeal Membrane Oxygenation in Pediatric Respiratory Failure. AB - Conventional treatment of respiratory failure involves positive pressure ventilation that can worsen lung damage. Extracorporeal membrane oxygenation (ECMO) is typically used when conventional therapy fails. In this study, we evaluated the use of venovenous (VV)-ECMO for the treatment of severe pediatric respiratory failure at our institution. A retrospective analysis of pediatric patients (age 1-18) placed on ECMO in the last 15 years (1999-2014) by the pediatric surgery team for respiratory failure was performed. Five pediatric patients underwent ECMO (mean age 10 years; range, 2-16). All underwent VV-ECMO. Diagnoses were status asthmaticus (2), acute respiratory distress syndrome due to septic shock (1), aspergillus pneumonia (1), and respiratory failure due to parainfluenza (1). Two patients had severe barotrauma prior to ECMO initiation. Average oxygenation index (OI) prior to cannulation was 74 (range 23-122). No patients required conversion to VA-ECMO. The average ECMO run time was 4.4 days (range 2-6). The average number of days on the ventilator was 15 (range 4-27). There were no major complications due to the procedure. Survival to discharge was 100%. Average follow up is 4.4 years (range 1-15). A short run of VV-ECMO can be lifesaving for pediatric patients in respiratory failure. Survival is excellent despite severely elevated oxygen indices. VV-ECMO may be well tolerated and can be considered for severe pediatric respiratory failure. PMID- 27670565 TI - Closure of a Traumatic Esophagomediastinal Fistula in a Child by Endoscopic Fulguration and Fibrin Injection. AB - Posttraumatic esophagomediastinal fistula is an uncommon clinical entity that warrants surgical awareness due to its life-threatening potential. Its management, especially in previously operated field, is controversial and several endoscopic methods are being proposed as alternatives. Ours is the first report of endoscopic fulguration and fibrin injection in successful closure of such fistula. A 9-year-old female sustained complete tracheoesophageal transection from a gunshot wound to the neck and underwent immediate primary repair. She presented nine months later with fevers and swelling over anterior neck. CT revealed air tracking posteriorly to the dorsal neck and inferiorly to the mediastinum. Considering difficulty of open surgical approach, endoscopic intervention was attempted. Posterior wall fistula was identified via microlaryngoscopy above the esophageal anastomosis. The fistula tract was de epithelialized via a Bugbee fulgurating electrode and then sealed with fibrin glue. Consequent imaging studies demonstrated complete occlusion of the fistula. Posterior posttraumatic esophagomediastinal fistula presents a challenging scenario from a surgical standpoint, as it combines difficulty of safe approach, high rate of injury to surrounding structures, and significant postoperative recurrence rate. Endoscopic Bugbee fulguration and fibrin glue injection are a safe and effective alternative to the traditional approach. PMID- 27670566 TI - Ileocolic and Jejunal Intussusceptions Requiring Surgical Intervention in a Pediatric Patient with Posttransplant Lymphoproliferative Disorder. AB - Posttransplant lymphoproliferative disorder (PTLD) is not uncommon in pediatrics. This case report describes a case of intestinal intussusception that occurred secondary to lymphoid hyperplasia in a child with PTLD following a cardiac transplant. This case was unique in its presentation with multiple areas of intussusception and with need for surgical intervention. The diagnosis of intussusception secondary to lead points from PTLD should be strongly considered in pediatric transplant patients presenting with abdominal complaints. PMID- 27670567 TI - Preoperative Bowel Preparation before Elective Bowel Resection or Ostomy Closure in the Pediatric Patient Population Has No Impact on Outcomes: A Prospective Randomized Study. AB - The role of preoperative bowel prep in the pediatric surgical population is uncertain. We performed a randomized prospective study to evaluate noninferiority between the presence or absence of a preoperative bowel prep in elective pediatric bowel surgery on postoperative outcomes. Patients aged three months to 18 years were recruited and randomized to the bowel prep group or the no bowel prep group. Patients were evaluated in-hospital and at postoperative clinic visits. Thirty-two patients were recruited; 18 in the bowel prep group and 14 in the no bowel prep group. There was no statistical difference (P > 0.05) in complications between the groups. Complications were observed in five patients in each group (27.8% and 35.7%, respectively). In the bowel prep group, two (11.1%) had wound infection (vs three, 21.4%), 0 had an intra-abdominal abscess (vs one, 7.1%), one (5.6%) had sepsis (vs one, 7.1%), one (5.6%) had an anastomotic leak (vs 0), and three (16.7%) had a bowel obstruction (vs one, 7.1%). There were no extra-abdominal complications. There were no significant differences in complications between the two groups. Further research is warranted, but may require a multi-institutional trial to recruit sufficient numbers to make conclusions about the significance of the need for bowel prep. PMID- 27670568 TI - Timing of Adjuvant Radioactive Iodine Therapy Does Not Affect Overall Survival in Low- and Intermediate-Risk Papillary Thyroid Carcinoma. AB - There is no consensus regarding the timing of adjuvant radioactive iodine therapy (RAI) therapy in low- and intermediate-risk papillary thyroid carcinoma (PTC). We analyzed the impact of adjuvant RAI on overall survival (OS) in low- and intermediate-risk PTC. The National Cancer Data Base was queried from 2004 to 2011 for pN0M0 PTC patients having near/subtotal or total thyroidectomy and adjuvant RAI. Tumors <=1 cm with negative margins were low risk while 1.1- to 4 cm tumors with negative margins or <=1 cm with microscopic margins were termed intermediate risk. RAI in <=3 months and between 3 and 12 months was termed as early and delayed, respectively. Survival analysis was performed after adjusting for patient and tumor-related variables. There were 7,306 low-risk and 16,609 intermediate-risk patients. Seventeen per cent low-risk and 15 per cent intermediate-risk patients had delayed RAI. Kaplan-Meier analysis did not show a difference in OS for early versus delayed RAI administration in low- (10-year OS 94.5% vs 94%, P = 0.627) or intermediate-risk (10-year OS 95.3% vs 95.9%, P = 0.944) patients. In adjusted survival analysis, RAI timing did not affect OS in all patients (hazard ratios = 0.98, 95% confidence interval = 0.71-1.34, P = 0.887). In conclusion, the timing of postthyroidectomy adjuvant RAI therapy does not affect OS in low- or intermediate-risk PTC. PMID- 27670569 TI - Malignancy Rate, Number Needed to Treat, and Positive Predictive Value for Breast MRI. AB - Breast MRI is being used more frequently for advanced screening for breast cancer. Patients may be at increased risk, or are symptomatic, with nonsuspicious mammograms. There is little data regarding the likelihood of a recommendation for biopsy, or for detecting a malignancy, in this population. We intended to determine the malignancy rate, number needed to treat, and positive predictive value for patients receiving adjunctive MRI at our institution. A retrospective review of all breast MRIs from 2008 to 2010 was done. Patients with any prior diagnosis of breast cancer, or BRCA+ were excluded. There were 324 patients. Most common reasons for ordering the breast MRI included: abnormal test result 130 (44%), palpable mass 74 (23%), family history 58 (18%), breast pain 47 (15%), and nipple discharge 45 (14%). Breast Imaging-Reporting and Data System score (BIRADS) was 1 or 2 in 36 per cent, 4 or 5 in 18 per cent, 3 in 26 per cent, 0 in 10 per cent, and not given in 9 per cent. Biopsy was recommended in 77 (24%), with biopsy actually performed in 57 (18%). Of the eight cancers identified, four (1.2%) were ductal carcinoma in situ (DCIS) and four (1.2%) were invasive cancer, yielding a true-positive rate of 2.5 per cent. Number needed to treat was 40. Positive predictive value was 14 per cent with a false-positive rate of 86 per cent. In this group of generally higher risk women, typically prescreened with mammography, 1.2 per cent had an invasive cancer, and another 1.2 per cent had DCIS. Those who undergo biopsy are 6.1 times more likely to have benign pathology. The efficacy of adjunctive breast MRI could be improved through refinements in indication, test interpretation, or alternative screening strategies. PMID- 27670570 TI - Arterial Injuries Associated with Blunt Fractures in the Lower Extremity. AB - Problems related to the combination of an arterial injury and a blunt fracture in the lower extremity are well known-delayed diagnosis, damaged soft tissue, and high amputation rate. The actual incidence of this injury pattern is, however, unknown. The purposes of this study were to determine the current incidence of named arterial injuries in patients with blunt fractures in the lower extremities and assess potential associated risk factors. This was a 7-year (2007-2013) retrospective review of patients >=18 years with blunt lower extremity fractures at a Level I trauma center. Fracture location and concomitant arterial injury were determined and patients stratified by age, gender, and injury velocity. Low injury velocity was defined as falls or assaults, whereas an injury secondary to a motorized vehicle was defined as high velocity. A total of 4413 patients (mean age 52.2 years, 54.3% male, mean Injury Severity Score 13.1) were identified. Forty-six patients (1.04%) had arterial injuries (20.4% common femoral, 8.2% superficial femoral, 44.9% popliteal, and 26.5% shank). After stratifying by age and injury velocity, younger age was associated with a significantly higher rate of vascular injury. For high-velocity injuries, there was no difference based on age. In conclusion, the prevalence of arterial injury after blunt lower extremity fractures is 1.04 per cent in our study. A significant paradoxical relationship exists between age and associated arterial injuries in patients with low-velocity injuries. If these data are confirmed in future studies, a low index of suspicion in patients >55 years after falls is appropriate. PMID- 27670571 TI - Use of a Novel Accounting and Grouping Method for Major Trunk Injury-Analysis of Data from a Statewide Trauma Financial Survey. AB - Major trunk trauma is common and costly, but comparisons of costs between trauma centers (TCs) are rare. Understanding cost is essential to improve quality, manage trauma service lines, and to facilitate institutional commitment for trauma. We have used results of a statewide trauma financial survey of Levels I to IV TC to develop a useful grouping method for costs and clinical characteristics of major trunk trauma. The trauma financial survey collected billing and clinical data on 75 per cent of the state trauma registry patients for fiscal year 2012. Cost was calculated by separately accounting for embedded costs of trauma response and verification, and then adjusting reasonable costs from the Medicare cost report for each TC. The cost-to-charge ratios were then recalculated and used to determine uniform cost estimates for each patient. From the 13,215 patients submitted for the survey, we selected 1,094 patients with major trunk trauma: lengths of stay >= 48 hours and a maximum injury of AIS >=3 for either thorax or abdominal trauma. These patients were then divided into three Injury Severity Score (ISS) groups of 9 to 15, 16 to 24, or 25+ to stratify patients into similar injury groups for analysis of cost and cost drivers. For abdominal injury, average total cost for patients with ISS 9 to 15 was $17,429. Total cost and cost per day increased with severity of injury, with $51,585 being the total cost for those with ISS 25. Similar trends existed for thoracic injury. Use of the Medicare cost report and cost-to-charge ratios to compute uniform costs with an innovative grouping method applied to data collected across a statewide trauma system provides unique information regarding cost and outcomes, which affects quality improvement, trauma service line management, and decisions on TC participation. PMID- 27670572 TI - The Colectomy Improvement Project: Do Evidence-Based Guidelines Improve Institutional Colectomy Outcomes? AB - This study evaluates whether increased adherence to eight specific practice parameters leads to improved outcomes in patients undergoing elective colorectal resections. In addition, we analyzed whether physicians with better compliance achieved better patient outcomes. Compliance to practice parameters and subsequent outcomes were compared between two groups relative to an educational intervention promoting the eight best practice guidelines selected. A total of 485 patients were identified over a 4-year period and were separated into a pre- (n = 273) and posteducation (n = 212) group. After the educational intervention, there was increased compliance in five of the eight practice parameters (P < 0.05). When outcomes where examined, the readmission rate (2.4% vs 8.4%; P = 0.005) and the incidence of deep surgical infections (0% vs 1.8%; P = 0.01) were significantly decreased when comparing the posteducational group to that of the group before intervention. A lower rate of anastomotic leaks were identified in the posteducation group, but this did not reach significance (1.9% vs 5.1%; P = .09). When analyzed individually, the most compliant physicians achieved better patient outcomes than their peers. Education of the operative team improved adherence to practice parameters and this may have contributed to improving patient outcomes. PMID- 27670573 TI - The Goalposts Have Moved: Can Surgery Residents Meet Updated Quality Benchmarks for Adenoma Detection Rate in Colonoscopy? AB - The American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology Task Force (ACGTF) on Quality in Endoscopy released updated quality benchmarks for colonoscopy in 2015. Our initial study concluded that surgery residents could perform safe and competent screening colonoscopy within a structured endoscopy curriculum. In this follow-up study, we sought to determine whether surgery residents could achieve the increased adenoma detection rate (ADR) benchmarks endorsed by the ASGE/ACGTF. An Institutional Review Board approved prospective analysis of colonoscopies performed by five postgraduate year 2 and 3 general surgery residents from 2013 to 2015 was completed. All colonoscopies were performed under the direct supervision of surgical endoscopists after each resident passed a structured endoscopy simulation curriculum. The following ASGE/ACG quality metrics were recorded: bowel preparation quality; cecal intubation rate; polyp and ADRs; and, complications. Power analysis determined that 108 procedures were required for an 80 per cent probability of data analysis accuracy. About 135 screening and diagnostic colonoscopies were performed. Bowel prep was considered "adequate" in 90 per cent of cases. The cecum was reached independently in 95 per cent of cases. Polyp(s) were visualized and removed in 39 per cent of patients. The overall ADR was 31.8 per cent (>25%). Male ADR was 38.7 per cent (>30%). Female ADR was 26.0 per cent (>20%). Average polyp size was 8.7 mm (range: 1-22 mm). One patient was readmitted for postpolypectomy syndrome, and successfully managed nonoperatively. In conclusion, using our structured endoscopy curriculum, surgery residents achieved ADRs fully consistent with the updated benchmark values endorsed by the ASGE/ACGTF. PMID- 27670574 TI - Neuropsychological Changes in Primary Hyperparathyroidism after Parathyroidectomy. AB - Neuropsychiatric symptoms (NPSs) of sporadic primary hyperparathyroidism (PHPT) are often subtle and effects of parathyroidectomy (PTX) on symptoms remains poorly characterized. Our aim was to evaluate effects of PTX on NPS in patients with PHPT. A prospective questionnaire was distributed to all patients undergoing PTX and to a thyroidectomy (TX) control group. The questionnaire included the validated scales Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) to assess for depression and anxiety respectively, as well as questions modified from Pasieka's Parathyroid Assessment of Symptoms (M-PAS). Point values were assigned to questionnaire answers to create a score, with a maximum of 63. Fifty-eight patients underwent PTX (58.6%) and 41 TX (41.4%). Mean preoperative scores were greater in PTX versus TX patients in total score, PHQ-9, GAD-7, and M-PAS (all P < 0.05). Post-PTX scores were lower than pre-PTX in total score, PHQ-9, GAD-7, and M-PAS (all P < 0.05), but not in pre- and post-TX. Post PTX 69.0 and 82.8 per cent of patients showed no symptoms of depression and anxiety, respectively, compared with 37.9 and 56.9 per cent pre-PTX. A total of 16.2 and 10.3 per cent of patients had moderately severe to severe depression and anxiety, which fell to 0 per cent post-PTX. NPSs are more common in patients with PHPT when compared with TX. Patients undergoing PTX have improvements in NPS. NPS scoring should occur in all patients with PHPT and severity of NPS should be considered a relative indication for PTX. PMID- 27670575 TI - Esophagectomy: Comparison of Short-Term Outcomes between Single-versus Two-Team Approach. AB - Literature about combining expertise of two specialties in esophageal cancer surgery is limited. We present the experience at a single institute comparing single-team (ST) versus two-team (TT) approach combining thoracic and abdominal surgeons. This is a retrospective study from a single tertiary care center. Data were collected from electronic medical records. Patients undergoing esophagectomy for esophageal cancer from November 2006 until August 2014 were included. The primary outcome measured was 30-day postoperative morbidity, secondary outcomes measured were operative time, intraoperative blood loss, and 30-day mortality. Results are reported as mean with an interquartile range. Forty-nine patients underwent esophagectomy by an ST and 51 patients by TT. Patient demographics, tumor characteristics, stage, pathology, and use of neoadjuvant therapy were comparable between groups. Charlson comorbidity index was significantly higher in TT group [3 (2, 4) vs 2 (2, 3), P = 0.02]. The TT group had a significantly shorter operative time compared to the ST group [304 (252,376) minutes vs 438 (375, 494] minutes, P < 0.0001). Intraoperative blood loss was 300 (200, 550) mL for the TT group and 250 (200,400) mL for the ST group (P = 0.29). There was no difference in 30-day postoperative morbidity (68.6% for TT, 59.2% for ST, P = 0.32) and mortality (2% each, P = 1) between the two groups. In conclusion, the operative time by the TT approach was significantly shorter than the ST approach with comparable postoperative morbidity and mortality. Long-term follow-up is needed to study this approach's effect on long-term survival. PMID- 27670576 TI - Development of Electronic Medical Record-Based "Rounds Report" Results in Improved Resident Efficiency, More Time for Direct Patient Care and Education, and Less Resident Duty Hour Violations. AB - Surgeons frequently report frustration and loss of efficiency with electronic medical record (EMR) systems. Together, surgery residents and a programmer at Augusta University created a rounds report (RR) summarizing 24 hours of vitals, intake/output, labs, and other values for each inpatient that were previously transcribed by hand. The objective of this study was to evaluate the RR's effect on surgery residents. Surgery residents were queried to assess the RR's impact. Outcome measures were time spent preparing for rounds, direct patient care time, educational activity time, rates of incorrect/incomplete data on rounds, and rate of duty hour violations. Hospital wide, 17,200 RRs were generated in the 1-month study. Twenty-three surgery residents participated. Time spent preparing for rounds decreased per floor patient (15.6 +/- 3.0 vs 6.0 +/- 1.2, P < 0.0001) and per intensive care unit patient (19.9 +/- 2.9 vs 7.5 +/- 1.2 P < 0.0001). The work day spent in direct patient care increased from 45.1 +/- 5.6 to 54.0 +/- 5.7 per cent (P = 0.0044). Educational activity time increased from 35.2 +/- 5.4 to 54.7 +/- 7.1 minutes per resident per day (P = 0.0004). Reported duty hour violations decreased 58 per cent (P < 0.0001). American Board of Surgery in Training exam scores trended up, and estimates of departmental annual financial savings range from $66,598 to $273,141 per year. Significant improvements occur with surgeon designed EMR tools like the RR. Hospitals and EMR companies should pair interested surgeons with health information technology developers to facilitate EMR enhancements. Improvements like RRs can have broad ranging, multidisciplinary impact and should be standard in all EMRs used for inpatient care at academic medical centers. PMID- 27670577 TI - Patients with Risk Factors for Complications Do Not Require Longer Antimicrobial Therapy for Complicated Intra-Abdominal Infection. AB - A prospective, multicenter, randomized controlled trial found that four days of antibiotics for source-controlled complicated intra-abdominal infection resulted in similar outcomes when compared with a longer duration. We hypothesized that patients with specific risk factors for complications also had similar outcomes. Short-course patients with obesity, diabetes, or Acute Physiology and Chronic Health Evaluation II >=15 from the STOP-IT trial were compared with longer duration patients. Outcomes included incidence of and days to infectious complications, mortality, and length of stay. Obese and diabetic patients had similar incidences of and days to surgical site infection, recurrent intra abdominal infection, extra-abdominal infection, and Clostridium difficile infection. Short- and long-course patients had similar incidences of complications among patients with Acute Physiology and Chronic Health Evaluation II >=15. However, there were fewer days to the diagnosis of surgical site infection (9.5 +/- 3.4 vs 21.6 +/- 6.2, P = 0.010) and extra-abdominal infection (12.4 +/- 6.9 vs 21.8 +/- 6.1, P = 0.029) in the short-course group. Mortality and length of stay was similar for all groups. A short course of antibiotics in complicated intra-abdominal infection with source control seems to have similar outcomes to a longer course in patients with diabetes, obesity, or increased severity of illness. PMID- 27670578 TI - Solving Set Cover with Pairs Problem using Quantum Annealing. AB - Here we consider using quantum annealing to solve Set Cover with Pairs (SCP), an NP-hard combinatorial optimization problem that plays an important role in networking, computational biology, and biochemistry. We show an explicit construction of Ising Hamiltonians whose ground states encode the solution of SCP instances. We numerically simulate the time-dependent Schrodinger equation in order to test the performance of quantum annealing for random instances and compare with that of simulated annealing. We also discuss explicit embedding strategies for realizing our Hamiltonian construction on the D-wave type restricted Ising Hamiltonian based on Chimera graphs. Our embedding on the Chimera graph preserves the structure of the original SCP instance and in particular, the embedding for general complete bipartite graphs and logical disjunctions may be of broader use than that the specific problem we deal with. PMID- 27670579 TI - Pharmacological Effects of Biotin in Animals. AB - In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. PMID- 27670580 TI - ent-Abietane Lactones from Euphorbia. AB - Extracted from Euphorbia, ent-Abietane lactones can be classified into several categories, such as Jolkinolides and Helioscopinolides, according to their structural features. The study of ent- Abietane lactones could date back to 1972, when Jolkinolide A and B were first isolated from Euphorbia jolkini Boiss. Since then, many other ent-Abietane lactones have been extracted from different species of Euphorbia. Their bio-activities include anti-tumor activity, anti-inflammatory activity as well as anti-bacterial activity. Among them, derivatives of Jolkinolide B draw the most attention for their high anti-tumor activity. There are many studies focus on the syntheses of Jolkinolides. In 1989, the first and efficient synthesis of Jolkinolides was accomplished by Katsumura et al. Their strategy to construct the last ring of Jolkinolides contributes a lot to the following studies. In the following thirty years, there are also other semi syntheses of Jolkinolides conducted, basing on different starting materials. In this review, we will give a brief clarification of ent-Abietane lactones, as well as their bio-activities and syntheses. PMID- 27670581 TI - Roles of Pyridine and Pyrimidine Derivatives as Privileged Scaffolds in Anticancer Agents. AB - BACKGROUND: Cancer has been considered to be a global health concern due to the impact of disease on the quality of life. The continual increase of cancer cases as well as the resistance of cancer cells to the existing drugs have driven the search for novel anticancer drugs with better potency and selectivity, improved pharmacokinetic profiles, and minimum toxicities. Pyridine and pyrimidine are presented in natural products and genetic materials. These pyridine/pyrimidine core structures have been noted for their roles in many biological processes as well as in cancer pathogenesis, which make such compounds become attractive scaffolds for discovery of novel drugs. RESULTS & CONCLUSION: In the recent years, pyridine- and pyrimidine-based anticancer drugs have been developed based on structural modification of these core structures (i.e., substitution with moieties and rings, conjugation with other compounds, and coordination with metal ions). Detailed discussion is provided in this review to highlight the potential of these small molecules as privileged scaffolds with attractive properties and biological activities for the search of novel anticancer agents. PMID- 27670582 TI - Tip60: Main Functions and Its Inhibitors. AB - BACKGROUND: Tip60, the founding member of MYST histone acetyltransferase family, was originally identified as a cellular acetyltransferase protein that interacts with HIV-1 Tat. Tip60 plays roles in many processes such as cellular signaling transmission, DNA damage repair, cell cycle and checkpoint control and apoptosis by acetylating its histone or non-histone substrates. RESULTS: Dysfunction of Tip60 could promote or suppress diseases including different kinds of cancers. CONCLUSION: Here, main functions and its known inhibitors were summarized. PMID- 27670583 TI - Assessing the Immunosafety of Engineered Nanoparticles with a Novel in Vitro Model Based on Human Primary Monocytes. AB - The possibility that nanomaterials could perturb the normal course of an inflammatory response is a key issue when assessing nanoimmunosafety. The alteration of the normal progress of an inflammatory response may have pathological consequences, since inflammation is a major defensive mechanism and its efficiency maintains the body's health. The immunosafety of engineered nanoparticles at nontoxic concentrations was investigated with the use of a human primary monocyte-based in vitro system, which reproduces in a simplified fashion the full course of the physiological inflammatory response, from initiation and development to resolution. The kinetics of expression and production of inflammatory and anti-inflammatory cytokines and the proteomic profiles were used for describing the inflammatory defensive response. We assessed the ability of gold and silver nanoparticles to trigger inflammation and to interfere with the course of an ongoing defensive reaction. While neither nanoparticle type was able to directly activate monocytes, silver nanoparticles could exacerbate the inflammatory response of monocytes but did not interfere with the resolution of the inflammatory reaction. These findings support the use of human primary monocyte-based in vitro assays for realistically investigating the effects of engineered nanoparticles on human innate immune responses, in order to predict the immunological risk of nanomaterials and implement safe nanoparticle-based applications. PMID- 27670584 TI - Effect of Transradial Catheterisation on Patency Rates of Radial Arteries Used as a Conduit for Coronary Bypass. AB - BACKGROUND: Transradial catheterisation is known to be associated with occlusion of the radial artery with an estimated incidence of 2-10% (1). There are very few studies looking at the patency of radial artery as a bypass graft after utilisation for catheterisation. METHODS: We conducted a retrospective review of patients undergoing coronary artery bypass grafting (CABG) utilising a radial artery graft. RESULTS: Long term patency rates were 59% in radial artery grafts utilised for catheterisation prior to CABG, compared to 78% if it were not (p= 0.035). CONCLUSION: Patency rates of radial artery grafts are significantly lower when the same radial artery was utilised for angiography prior to coronary artery bypass grafting (CABG). PMID- 27670585 TI - Cardiac Perforation by Migrated Fractured Strut of Inferior Vena Cava Filter Mimicking Acute Coronary Syndrome. AB - We present a rare late complication after inferior vena cava filter (IVC) placement. A 52-year-old woman with an IVC presented with sudden onset of chest pain. Cardiac catheterisation and echocardiography revealed an embolised IVC filter strut penetrating the right ventricle. Endovascular retrieval was considered but deemed unsafe due to proximity to the right coronary artery and concern for migration to pulmonary circulation. Urgent removal of the strut was performed via sternotomy. The postoperative course was uneventful. Two weeks later, she was asymptomatic. Minimally invasive approaches have been described for retrieval of intact IVC filters that have migrated to the right heart but not for embolised filter fragments. We recommend traditional sternotomy as the preferred method of retrieval as it limits the likelihood of further migration or trauma. PMID- 27670586 TI - Acute Haemodynamic and Echocardiographic Effects of Multiple Configurations of Left Ventricular Pacing Sites in Acute Myocardial Infarction: Experimental Study. AB - BACKGROUND: Left ventricular (LV) pacing is unsuccessful in a significant number of patients, mainly due to sub-optimal LV pacing location. Nevertheless, data about the impact of different pacing sites on LV function in ischaemic myocardium are scarce. The purpose of this study was to investigate the effect of combinations of alternative LV pacing sites on LV mechanics after experimental acute anterior myocardial infarction (AMI), in order to define the optimal configuration. METHODS: Atrioventricular epicardial pacing at alternative pacing sites was performed in 16 healthy pigs simultaneously, after experimental AMI. Standard right ventricular (RV) apical pacing was combined with: i) LV apex lateral wall; ii) LV basal posterior wall; iii) LV basal anterior wall, and; iv) LV basal anterior wall + LV basal posterior wall. Moreover the pacing configurations of, v) LV basal posterior wall + LV apex lateral wall; vi) LV basal posterior wall + LV basal anterior wall, and; vii) LV basal anterior wall + LV apex lateral wall were also investigated. Haemodynamic parameters, together with classic and novel echocardiographic indices were used, to evaluate the effect of each pacing combination. A speckle tracking technique using EchoPAC software was used. RESULTS: After AMI, the pacing combination of LV apex lateral wall and LV basal posterior wall had the most favourable effect on LV function, leading to similar haemodynamic and torsional effects with sinus rhythm (all variables p>0.05). CONCLUSIONS: In pig hearts after AMI, the combination of pacing LV apex lateral wall and LV basal posterior wall managed to maintain the LV function at a level comparable to the sinus rhythm. PMID- 27670587 TI - AC220 and AraC cause differential inhibitory dynamics in patient-derived M5-AML with FLT3-ITD and, thus, ultimately distinct therapeutic outcomes. AB - Engrafting the bone marrow cells of a patient with M5 acute myeloid leukemia into immunocompromised mice (AM7577) resulted in serially transferrable stable AML and eventual mortality. The disease starts in the bone marrow and then expands to peripheral areas, which is typical of M5 leukemogenesis, where high leukemic burden in blood is coincident with symptoms/mortality. The leukemic cells in the mice had myeloid morphology, phenotypes, and genotypes (including the internal tandem duplication of FMS-like tyrosine kinase receptor 3 gene [FLT3-ITD]) similar to those of the original patient. Autocrine mechanisms of human granulocyte-macrophage colony-stimulating factor/interleukin-3 likely support AM7577 growth in mice. Treatment with FLT3 TKI (AC220) caused complete remission in peripheral blood, spleen, and bone, along with relief of symptoms and extended life, hinting that FLT3-ITD may be a key leukemogenic driver maintaining the disease. Interestingly, withdrawal of AC220 (high dose) did not result in relapse of disease, suggesting cure. These results, however, are in contrast to cytarabine (AraC) induction treatment: First, although AraC significantly suppresses the diseases in blood, and to a lesser degree in bone marrow and spleen, the suppression is temporary and does not prevent eventual onset of disease/death. Second, the withdrawal of AraC always resulted in rapid relapse in peripheral blood and eventually death. Our observation in this patient-derived model may provide useful information for clinical applications of the two drugs. PMID- 27670588 TI - Modeling of occupational exposure to accidentally released manufactured nanomaterials in a production facility and calculation of internal doses by inhalation. AB - BACKGROUND: Occupational exposure to manufactured nanomaterials (MNMs) and its potential health impacts are of scientific and practical interest, as previous epidemiological studies associate exposure to nanoparticles with health effects, including increased morbidity of the respiratory and the circulatory system. OBJECTIVES: To estimate the occupational exposure and effective internal doses in a real production facility of TiO2 MNMs during hypothetical scenarios of accidental release. METHODS: Commercial software for geometry and mesh generation, as well as fluid flow and particle dispersion calculation, were used to estimate occupational exposure to MNMs. The results were introduced to in house software to calculate internal doses in the human respiratory tract by inhalation. RESULTS: Depending on the accidental scenario, different areas of the production facility were affected by the released MNMs, with a higher dose exposure among individuals closer to the particles source. CONCLUSIONS: Granted that the study of the accidental release of particles can only be performed by chance, this numerical approach provides valuable information regarding occupational exposure and contributes to better protection of personnel. The methodology can be used to identify occupational settings where the exposure to MNMs would be high during accidents, providing insight to health and safety officials. PMID- 27670589 TI - HEALTH TECHNOLOGY ASSESSMENT OF MEDICAL DEVICES IN EUROPE: PROCESSES, PRACTICES, AND METHODS. AB - OBJECTIVES: To review and compare current Health Technology Assessment (HTA) activities for medical devices (MDs) across European HTA institutions. METHODS: A comprehensive approach was adopted to identify institutions involved in HTA in European countries. We systematically searched institutional Web sites and other online sources by using a structured tool to extract information on the role and link to decision making, structure, scope, process, methodological approach, and available HTA reports for each included institution. RESULTS: Information was obtained from eighty-four institutions, forty-seven of which were analyzed. Fifty four methodological documents from twenty-three agencies in eighteen countries were identified. Only five agencies had separate documents for the assessment of MDs. A few agencies made separate provisions for the assessment of MDs in their general methods. The amount of publicly available HTA reports on MDs varied by device category and agency remit. CONCLUSIONS: Despite growing consensus on their importance and international initiatives, such as the EUnetHTA Core Model(r), specific tools for the assessment of MDs are rarely developed and implemented at the national level. Separate additional signposts incorporated in existing general methods guides may be sufficient for the evaluation of MDs. PMID- 27670590 TI - Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity. AB - Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecule expressed in covariance with the regulatory module of Th17 cells. Although PROCR expression in T cells was controlled by the cooperative action of the Th17 lineage-specific transcription factors RORgammat, IRF4, and STAT3, PROCR negatively regulated Th17 differentiation. CD4+ T cells from PROCR low expressor mutant mice readily differentiated into Th17 cells, whereas addition of the PROCR ligand, activated protein C, inhibited Th17 differentiation in vitro. In addition, PROCR acted as a negative regulator of Th17 pathogenicity in that it down-regulated expression of several pathogenic signature genes, including IL-1 and IL-23 receptors. Furthermore, T cell-specific deficiency of PROCR resulted in the exacerbation of experimental autoimmune encephalomyelitis (EAE) and higher frequencies of Th17 cell in vivo, indicating that PROCR also inhibits pathogenicity of Th17 cells in vivo. PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells. PMID- 27670591 TI - IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21 producing B helper CD8+ T cells. AB - IL-6 is known to contribute to the differentiation of CD4+ T cells into different subsets of effector T helper cells. Less is known about the potential of IL-6 in regulating CD8+ T cell effector function. Here, we identify IL-6 as a master regulator of IL-21 in effector CD8+ T cells. IL-6 promotes the differentiation of a subset of naive CD8+ T cells that express IL-6R into a unique population of effector CD8+ T cells characterized by the production of high levels of IL-21 and low levels of IFN-gamma. Similar to CD4+ T follicular helper (Tfh) cells, IL-21 producing CD8+ T cells generated in the presence of IL-6 directly provide help to B cells to induce isotype switching. CD8+ T cell-derived IL-21 contributes to the production of protective virus-specific IgG antibodies during influenza virus infection. Thus, this study reveals the presence of a new mechanism by which IL-6 regulates antibody production during viral infection, and a novel function of effector CD8+ T cells in the protection against viruses. PMID- 27670593 TI - The aryl hydrocarbon receptor is required for the maintenance of liver-resident natural killer cells. AB - A tissue-resident population of natural killer cells (NK cells) in the liver has recently been described to have the unique capacity to confer immunological memory in the form of hapten-specific contact hypersensitivity independent of T and B cells. Factors regulating the development and maintenance of these liver resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut. In this study, we show that liver-resident NK (NK1.1+CD3-) cells, defined as CD49a+TRAIL+CXCR6+DX5- cells in the mouse liver, constitutively express AhR. In AhR-/- mice, there is a significant reduction in the proportion and absolute number of these cells, which results from a cell-intrinsic dependence on AhR. This deficiency in liver-resident NK cells appears to be the result of higher turnover and increased susceptibility to cytokine-induced cell death. Finally, we show that this deficiency has functional implications in vivo. Upon hapten exposure, AhR-/- mice are not able to mount an NK cell memory response to hapten rechallenge. Together, these data demonstrate the requirement of AhR for the maintenance of CD49a+TRAIL+CXCR6+DX5- liver-resident NK cells and their hapten memory function. PMID- 27670592 TI - Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. AB - Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. In this study, we observed expression of a cytoplasmic PLA2 (PLA2G4D) in psoriatic mast cells but, unexpectedly, also found PLA2G4D activity to be extracellular. This was explained by IFN-alpha-induced mast cell release of exosomes, which transferred cytoplasmic PLA2 activity to neighboring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid-specific CD1a-reactive T cells inducing production of IL-22 and IL-17A. Circulating and skin-derived T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared with healthy controls. Overall, these data present an alternative model of psoriasis pathogenesis in which lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA2 inhibition or CD1a blockade may have therapeutic potential for psoriasis. PMID- 27670595 TI - Comparative study of the intake of toxic persistent and semi persistent pollutants through the consumption of fish and seafood from two modes of production (wild-caught and farmed). AB - Adverse effects of chemical contaminants associated with seafood counteract the undoubted benefits for the health of its valuable nutrients. So much so that many dietary guidelines recommend no more than one serving a week of fish and seafood. Although is estimated that aquaculture provides more than 50% of the fish and seafood consumed globally, few research studies have focused in the assessment of the intake of pollutants through aquaculture products. In this study we determined the levels of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and toxic elements (Pb, Cd, Ni, Al, As, and Hg) in a large sample of farmed and wild-caught seafood, and we estimated the intake of these contaminants in two hypothetical models of consumers: those consuming only farmed fish, and those consuming only wild fish. Measured levels of most organic and many inorganic pollutants were higher in aquaculture products, and consequently intake levels if only such products were consumed would be also significantly higher. Thus, the intake of ?PAHs in adults consuming aquaculture seafood would be 3.30ng/kg-bw/day, and consuming seafood from extractive fishing 2.41ng/kg-bw/day (p<0.05); ?OCPs, 3.36 vs. 1.85ng/kg bw/day, respectively (p<0.05); ?PCBs, 2.35 vs. 2.11ng/kgbw/day, respectively; and the intake of Pb, Ni, As, and Al would be also significantly higher consuming farmed seafood. For children the estimations were very similar, but the difference of intake of PCBs reached statistical significance. The implementation of several decontamination practices in aquaculture would allow not only match the levels of pollution from wild-caught seafood, but also could provide products with much lower levels of pollutants than those, which in turn would allow to increase consumption over the "one serving per week", and so benefit the consumer of the enormous positive health effects of the valuable nutrients of seafood. PMID- 27670596 TI - Association between heavy metal exposure and poor working memory and possible mediation effect of antioxidant defenses during aging. AB - BACKGROUND: Inverse associations have been observed between memory performance and blood concentrations of cadmium (Cd) and lead (Pb). Low antioxidant cell activity has also been linked to decline in memory due to aging. However, it has not yet been established whether the heavy metal-memory relationship is mediated by differences in antioxidant activity. METHODS: We examined Cd and Pb levels, as well as oxidative stress parameters, in blood samples from 125 older adults (age range 50-82years). The Counting Span Test (CST) was used to evaluate working memory capacity (WMC). The Monte Carlo Method for Assessing Mediation (MCMAM) was used to analyze the mediation role of antioxidant activity in the heavy metals memory association. RESULTS: High blood Cd (BCd) concentration alone, and in combination with elevated blood Pb (BPb) concentration, was associated with poor WMC (p<=0.001) and low enzymatic antioxidant defenses (p>=0.006). The variance in WMC accounted for by BCd or by BCd combine with BPb was 20.6% and 18.6%, respectively. The MCMAM revealed that the influence of BCd and BPb concentrations on WMC was mediated by low antioxidant capacity (confidence interval - CI: 0.072 to -0.064 for BCd; CI: -0.062 to -0.045 for BPb). CONCLUSION: These findings showed Pb and Cd blood concentration in older adults, even at levels below the current recommended threshold, was negatively associated with WMC and that this relationship may be partly mediated by low antioxidant defenses. Knowledge on the environmental factors that negatively influence brain and cognition during aging can help inform public policy strategies to prevent and control the adverse effects of environmental contaminant exposure during aging. PMID- 27670597 TI - Effect of past peat cultivation practices on present dynamics of dissolved organic carbon. AB - Peatlands are a major source of dissolved organic carbon (DOC) for aquatic ecosystems. Naturally high DOC concentrations in peatlands may be increased further by drainage. For agricultural purposes, peat has frequently been mixed with sand, but the effect of this measure on the release and cycling of DOC has rarely been investigated. This study examined the effects of (i) mixing peat with sand and (ii) water table depth (WTD) on DOC concentrations at three grassland sites on shallow organic soils. The soil solution was sampled bi-weekly for two years with suction plates at 15, 30 and 60cm depth. Selected samples were analysed for dissolved organic nitrogen (DON), delta13CDOM and delta15NDOM. Average DOC concentrations were surprisingly high, ranging from 161 to 192mgl-1. There was no significant impact of soil organic carbon (SOC) content or WTD on mean DOC concentrations. At all sites, DOC concentrations were highest at the boundary between the SOC-rich horizon and the mineral subsoil. In contrast to the mean concentrations, the temporal patterns of DOC concentrations, their drivers and the properties of dissolved organic matter (DOM) differed between peat-sand mixtures and peat. DOC concentrations responded to changes in environmental conditions, but only after a lag period of a few weeks. At the sites with a peat sand mixture, temperature and therefore probably biological activity determined the DOC concentrations. At the peat site, the contribution of vegetation-derived DOM was higher. The highest concentrations occurred during long, cool periods of waterlogging, suggesting a stronger physicochemical-based DOC mobilisation. Overall, these results indicate that mixing peat with sand does not improve water quality and may result in DOC losses of around 200kg DOCha-1a-1. PMID- 27670594 TI - Calorie restriction protects against experimental abdominal aortic aneurysms in mice. AB - Abdominal aortic aneurysm (AAA), characterized by a localized dilation of the abdominal aorta, is a life-threatening vascular pathology. Because of the current lack of effective treatment for AAA rupture, prevention is of prime importance for AAA management. Calorie restriction (CR) is a nonpharmacological intervention that delays the aging process and provides various health benefits. However, whether CR prevents AAA formation remains untested. In this study, we subjected Apoe-/- mice to 12 wk of CR and then examined the incidence of angiotensin II (AngII)-induced AAA formation. We found that CR markedly reduced the incidence of AAA formation and attenuated aortic elastin degradation in Apoe-/- mice. The expression and activity of Sirtuin 1 (SIRT1), a key metabolism/energy sensor, were up-regulated in vascular smooth muscle cells (VSMCs) upon CR. Importantly, the specific ablation of SIRT1 in smooth muscle cells abolished the preventive effect of CR on AAA formation in Apoe-/- mice. Mechanistically, VSMC-SIRT1 dependent deacetylation of histone H3 lysine 9 on the matrix metallopeptidase 2 (Mmp2) promoter was required for CR-mediated suppression of AngII-induced MMP2 expression. Together, our findings suggest that CR may be an effective intervention that protects against AAA formation. PMID- 27670598 TI - Cultural Adaptation of Minimally Guided Interventions for Common Mental Disorders: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Cultural adaptation of mental health care interventions is key, particularly when there is little or no therapist interaction. There is little published information on the methods of adaptation of bibliotherapy and e-mental health interventions. OBJECTIVE: To systematically search for evidence of the effectiveness of minimally guided interventions for the treatment of common mental disorders among culturally diverse people with common mental disorders; to analyze the extent and effects of cultural adaptation of minimally guided interventions for the treatment of common mental disorders. METHODS: We searched Embase, PubMed, the Cochrane Library, and PsycINFO for randomized controlled trials that tested the efficacy of minimally guided or self-help interventions for depression or anxiety among culturally diverse populations. We calculated pooled standardized mean differences using a random-effects model. In addition, we administered a questionnaire to the authors of primary studies to assess the cultural adaptation methods used in the included primary studies. We entered this information into a meta-regression to investigate effects of the extent of adaptation on intervention efficacy. RESULTS: We included eight randomized controlled trials (RCTs) out of the 4911 potentially eligible records identified by the search: four on e-mental health and four on bibliotherapy. The extent of cultural adaptation varied across the studies, with language translation and use of metaphors being the most frequently applied elements of adaptation. The pooled standardized mean difference for primary outcome measures of depression and anxiety was -0.81 (95% CI -0.10 to -0.62). Higher cultural adaptation scores were significantly associated with greater effect sizes (P=.04). CONCLUSIONS: Our results support the results of previous systematic reviews on the cultural adaptation of face-to-face interventions: the extent of cultural adaptation has an effect on intervention efficacy. More research is warranted to explore how cultural adaptation may contribute to improve the acceptability and effectiveness of minimally guided psychological interventions for common mental disorders. PMID- 27670599 TI - Crohn's Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab. AB - OBJECTIVES: Anti-tumor necrosis factor (TNF) drugs are commonly used to treat moderate-to-severe Crohn's disease (CD). Both the activity of CD and the concomitant immunosuppressants (corticosteroids and immunomodulators) used with anti-TNF drugs could increase the risk of infection. We determined the relative risk of serious and opportunistic infections associated with increasing disease activity and concomitant immunomodulators and corticosteroids in patients with CD treated with adalimumab. METHODS: This pooled analysis identified incident treatment-emergent serious and opportunistic infections among patients with CD in clinical trials of adalimumab. Disease activity was assessed with the Crohn's Disease Activity Index (CDAI). RESULTS: The analysis included 2,266 patients treated with adalimumab with median age 35 years. Higher disease activity was associated with significantly increased risks of both serious and opportunistic infections at 1 year, with each 100-point increase in CDAI associated with a >30% increased risk of each type of infection. Concomitant use of immunomodulators was associated with a significant >3-fold decreased risk of serious infection (hazard ratio (HR) 0.29 (0.08-0.98), P=0.045) by 1 year. Concomitant use of corticosteroids was associated with a significantly increased risk of serious infection by day 120 (HR 2.40 (1.33-4.35), P=0.004). Concomitant use of either category of immmunosuppressant was associated with numerically higher rates of opportunistic infection, 40% of which were due to herpes zoster, compared with adalimumab monotherapy. CONCLUSIONS: Higher disease activity in CD is associated with significantly increased risks of both serious and opportunistic infections. In addition to corticosteroid-sparing strategies, consideration should be given to expanding herpes zoster vaccination guidelines to include younger patients. PMID- 27670600 TI - Risk and Predictors of Variceal Bleeding in Cirrhosis Patients Receiving Primary Prophylaxis With Non-Selective Beta-Blockers. AB - OBJECTIVES: Prior studies have demonstrated the efficacy of non-selective beta blockers (NSBB) in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of NSBB in routine clinical care. METHODS: We conducted a retrospective cohort study of cirrhotic patients without prior bleeding who initiated a NSBB (propranolol, nadolol) at any Veterans Administration facility between 2008 and 2013. The primary outcome was variceal bleeding within 12 months. We conducted Cox-proportional hazards analyses to identify demographic, clinical, and NSBB-related (type of NSBB, mean dose, dose change, and heart rate response) factors associated with variceal bleeding. RESULTS: Of 5,775 patients, 678 (11.7%) developed variceal bleeding. Mean daily dose of NSBB was <40 mg in 58.8%, 18.1% had either upward or downward titration in NSBB dose, and 9.8% had hemodynamic response. Patients who were younger, with ascites, greater medical comorbidity, and higher MELD (Model for end-stage liver disease) scores had a higher risk of variceal bleeding. Patients on a higher daily dose (>60 vs. <40 mg, adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.51-0.81), who had either upward or downward dose titration (adjusted HR 0.69; 95% CI: 0.52-0.90 and 0.64; 95% CI 0.45-0.90, respectively), and those who achieved hemodynamic response (adjusted HR 0.75; 95% CI=0.57-1.0) had lower risk. CONCLUSIONS: Approximately 12% of patients bled while being on NSBB for primary prophylaxis. A higher NSBB dose and dose titration were protective; yet most patients did not have the NSBB dose titrated to the recommended levels. Our data highlight the need for careful monitoring of cirrhotic patients on NSBB. PMID- 27670601 TI - Diagnostic and Therapeutic Endoscopic Retrograde Cholangiography Using a Short Type Double-Balloon Endoscope in Patients With Altered Gastrointestinal Anatomy: A Multicenter Prospective Study in Japan. AB - OBJECTIVES: To evaluate the utility and safety of a short-type double-balloon endoscope (DBE) in the treatment of biliary disease in patients with surgically altered gastrointestinal (GI) anatomy. METHODS: This study was conducted as a multicenter, single-arm, prospective trial at five tertiary academic care centers and three community-based hospitals in Japan. Consecutive patients with biliary disease with altered GI anatomy were prospectively included in this study. RESULTS: A total of 311 patients underwent double-balloon endoscopic retrograde cholangiography (ERC). The success rate of reaching the target site, the primary end point, was 97.7% (95% confidence interval (CI): 95.4-99.1). The success rate of biliary cannulation and contrast injection of the targeted duct, the secondary end point, was 96.4% (95% CI: 93.6-98.2), and the therapeutic success rate was 97.9% (95% CI: 95.4-99.2). Adverse events occurred in 33 patients (10.6%, 95% CI: 7.1-14.0) and were managed conservatively in all patients with the exception of 1 in whom a perforation developed, requiring emergency surgery. CONCLUSIONS: ERC using a short-type DBE resulted in an excellent therapeutic success rate and a low rate of adverse events. This treatment can be a first-line treatment for biliary disease in patients with surgically altered GI anatomy. PMID- 27670602 TI - Biomarkers in Search of Precision Medicine in IBD. AB - The completion of the human genome project in 2003 represented a major scientific landmark, ushering in a new era with hopes and expectations of fresh insights into disease mechanisms and treatments. In inflammatory bowel disease (IBD), many important discoveries soon followed, notably the identification of >200 genetic susceptibility loci and characterization of the gut microbiome. As "big data", driven by advances in technology, becomes increasingly available and affordable, individuals with IBD and clinicians alike yearn for tangible outcomes from the promise of "precision medicine"-precise diagnosis, monitoring, and treatment. Here, we provide a commentary on the prospects and challenges of precision medicine and biomarkers in IBD. We focus on the three key areas where precision IBD will have the most impact: (1) disease susceptibility, activity, and behavior; (2) prediction of drug response and adverse effects; and (3) identification of subphenotypic mechanisms to facilitate drug discovery and selection of new treatments in IBD. PMID- 27670603 TI - Rescue Therapy for Helicobacter pylori Eradication: A Randomized Non-Inferiority Trial of Amoxicillin or Tetracycline in Bismuth Quadruple Therapy. AB - OBJECTIVES: To compare the efficacy and safety of bismuth-containing quadruple therapy with tetracycline or amoxicillin for rescue treatment of Helicobacter pylori. METHODS: The study was a non-inferiority trial of H. pylori eradication with at least two previous treatment failures. Subjects were randomized to receive 14-day therapy with b.i.d. lansoprazole 30 mg and bismuth 220 mg, plus metronidazole 400 mg q.i.d and amoxicillin 1 g t.i.d (amoxicillin group) or tetracycline 500 mg q.i.d (tetracycline group). Antimicrobial susceptibility was assessed by the agar-dilution method. Primary outcome was H. pylori eradication at 6 weeks after treatment. RESULTS: In all, 312 subjects were randomized, 13 were lost to follow-up; 29 violated the protocol. The intention-to-treat, per protocol, and modified intention-to-treat eradication rates were (amoxicillin) 88.5% (138/156, 95% confidence interval (CI) 83.4-93.5%), 93.7% (133/142, 95% CI 89.7-97.7%), and 92.6% (138/149, 95% CI 88.4-96.8%). With tetracycline, they were 87.2% (136/156, 95% CI 81.9-92.4%), 95.3% (122/128, 95% CI 91.7-99.0%), and 90.7% (136/150, 95% CI 86.0-95.3%). Amoxicillin-, tetracycline-, and metronidazole resistant rates were 8.3, 1.0, and 87.8%, respectively. Non-inferiority was confirmed (P<0.025). Metronidazole resistance did not affect the efficacy of either therapy. Compliance was greater and moderate and severe adverse events were less among those receiving amoxicillin than those receiving tetracycline. CONCLUSIONS: The novel bismuth-containing quadruple therapy with metronidazole and amoxicillin is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment as it provides similar eradication with superior safety and compliance. PMID- 27670604 TI - Refining Mild-to-Moderate Alzheimer Disease Screening: A Tool for Clinicians. AB - OBJECTIVES: Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population. DESIGN: Data were obtained from two independent, longitudinal, observational multicenter studies in patients with mild-to-moderate AD. SETTING: The two studies were the European "Impact of Cholinergic Treatment Use" (ICTUS) and the French "REseau sur la maladie d'Alzheimer FRancais" (REAL.FR). PARTICIPANTS: We used prospective data of 756 patients enrolled in ICTUS and 340 enrolled in REAL.FR. MEASUREMENTS: A prediction rule of cognitive decline was derived on ICTUS using classification and regression tree analysis and then cross-validated on REAL.FR. A range of demographic, clinical and cognitive variables were tested as predictor variables. RESULTS: Overall, 27.9% of patients in ICTUS and 20.9% in REAL.FR did not decline over 2 years. We identified optimized cut-points on the verbal memory items of the Alzheimer Disease Assessment Scale-Cognitive Subscale capable of classifying patients at baseline into those who went on to decline and those who remained stable or improved over the duration of the trial. CONCLUSION: The application of this simple rule would allow the identification of dementia cases where a more detailed differential diagnostic examination (eg, with biomarkers) is warranted. These findings are promising toward the refinement of AD screening in the clinic. For a further optimization of our classification rule, we encourage others to use our methodological approach on other episodic memory assessment tools designed to detect even small cognitive changes in patients with AD. PMID- 27670606 TI - Comment on: "Timing of cranioplasty: is early surgery associated with increased complications and poor outcome?" PMID- 27670605 TI - Protein Supplementation Does Not Significantly Augment the Effects of Resistance Exercise Training in Older Adults: A Systematic Review. AB - BACKGROUND AND AIMS: Physical activity and nutritional supplementation interventions may be used to ameliorate age-related loss of skeletal muscle mass and function. Previous reviews have demonstrated the beneficial effects of resistance exercise training (RET) combined with protein or essential amino acids (EAA) in younger populations. Whether or not older adults also benefit is unclear. The aim of this review was to determine whether regular dietary supplementation with protein/EAA during a RET regimen augments the effects of RET on skeletal muscle in older adults. METHODS: A literature search was conducted in August 2015 using MEDLINE, EMBASE, SPORTDiscus, and CINAHL Plus to identify all controlled trials using a RET regimen with and without protein/EAA supplementation. Outcome variables included muscle strength, muscle size, functional ability, and body composition. RESULTS: Fifteen studies fulfilled the eligibility criteria, including 917 participants with a mean age of 77.4 years. Studies involving both healthy participants and those described as frail or sarcopenic were included. Overall, results indicated that protein supplementation did not significantly augment the effects of RET on any of the specified outcomes. Exceptions included some measures of muscle strength (3 studies) and body composition (2 studies). Meta-analyses were conducted but were limited because of methodologic differences between studies, and results were inconclusive. CONCLUSIONS: Systematic review and meta-analysis of controlled trials reveal that protein/EAA supplementation does not significantly augment the effects of progressive RET in older adults. PMID- 27670608 TI - Synthesis of Hindered Anilines: Three-Component Coupling of Arylboronic Acids, tert-Butyl Nitrite, and Alkyl Bromides. AB - The synthesis of sterically hindered amines has been a significant challenge in organic chemistry. Herein, we report a modular, three-component coupling that constructs two carbon-nitrogen bonds including a sterically hindered Csp3-N bond using commercially available materials. This process uses an earth-abundant copper catalyst and mild reaction conditions, allowing access to a variety of complex aromatic amines. PMID- 27670610 TI - Skin-Specific Deletion of Mis18alpha Impedes Proliferation and Stratification of Epidermal Keratinocytes. AB - The Mis18 proteins (Mis18alpha, Mis18beta, and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development. Here, we show that Mis18alpha is critical for the proliferation of keratinocytes and stratification of the epidermis. Mice lacking Mis18alpha in the epidermis died shortly after birth, showing skin abnormalities like thin and translucent skin and defective skin barrier functions. The epidermis of newborn Mis18alpha-deficient mice lacked distinct stratification and mature hair follicles, with a reduction in the number of proliferating cells and increased cell death in the basal layer. Earlier expression of the Cre recombinase from keratin-14 promoter in the ventral region resulted in earlier keratinocyte death in the ventral part compared with the dorsal part in the absence of Mis18alpha, leading to more severe malformation of the ventral epidermal layers. As observed in Mis18alpha-deficient mouse keratinocytes, knockdown of Mis18alpha in HaCaT cells caused marked loss of centromeric CENP-A dots and chromosomal misalignment. Overall, we propose that Mis18alpha is important for epidermal cell proliferation and stratification, because it is required for the deposition of CENP-A at the centromeric nucleosomes. PMID- 27670611 TI - Kidney cancer: Micrometastases detectable using flow cytometry. PMID- 27670607 TI - Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily. AB - Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP). We carried out a series of experiments to map out and learn from the differences and similarities between these enzymes. First, we asked why there would be independent instances of monoesterases in the AP superfamily? PafA has a much weaker product inhibition and slightly higher activity relative to EcAP, suggesting that different metabolic evolutionary pressures favored distinct active-site architectures. Next, we addressed the preferential phosphate monoester and diester catalysis of PafA and NPP, respectively. We asked whether the >80% sequence differences throughout these scaffolds provide functional specialization for each enzyme's cognate reaction. In contrast to expectations from this model, PafA and NPP mutants with the common subset of active-site groups embedded in each native scaffold had the same monoesterase:diesterase specificities; thus, the >107-fold difference in native specificities appears to arise from distinct interactions at a single phosphoryl substituent. We also uncovered striking mechanistic similarities between the PafA and EcAP monoesterases, including evidence for ground-state destabilization and functional active-site networks that involve different active-site groups but may play analogous catalytic roles. Discovering common network functions may reveal active site architectural connections that are critical for function, and identifying regions of functional modularity may facilitate the design of new enzymes from existing promiscuous templates. More generally, comparative enzymology and analysis of catalytic promiscuity can provide mechanistic and evolutionary insights. PMID- 27670612 TI - Urinary incontinence: Use of alpha-blockers plus desmopressin is safe. PMID- 27670609 TI - Slug Modulates UV Radiation-Induced Cutaneous Inflammation by Regulating Epidermal Production of Proinflammatory Cytokines. PMID- 27670613 TI - BPH: Disrupting AR signalling promotes inflammation. PMID- 27670614 TI - Kidney cancer: HIF-2alpha - a new target in RCC. PMID- 27670615 TI - Testicular cancer: Radiotherapy increases pancreatic cancer risk. PMID- 27670616 TI - Bladder cancer: Rho-sensitive pathway mediates metastasis. PMID- 27670617 TI - Prostate cancer: Circulating miRNAs indicate high-risk disease. PMID- 27670620 TI - Qualitatively different memory states in Lymnaea as shown by differential responses to propranolol. AB - Mixed results with the synthetic beta-adrenergic receptor blocker, propranolol, have been reported in human populations with regards to its therapeutic efficacy for PTSD treatments targeting the memory reconsolidation process. Stress alters the ability to form and maintain memory, but whether the causal neuronal mechanisms underling memory formation in PTSD are similar to normal memory is not clear. Here, we use Lymnaea to study the effects of combinations of stressors on the quality of the formed memory state. We show reactivation dependent pharmacologic disruption of reconsolidation using propranolol in Lymnaea; specifically, we show that only certain memories created under conditions of a combination of stressors are susceptible to disruption. Our data suggest that phenotypically similar memories may be molecularly diverse, depending on the conditions under which they are formed. Applied to human PTSD, this could account for the mixed results in the literature on disrupting reconsolidation with propranolol. PMID- 27670619 TI - Cholinergic neurodegeneration in an Alzheimer mouse model overexpressing amyloid precursor protein with the Swedish-Dutch-Iowa mutations. AB - Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is mainly characterized by beta-amyloid (Abeta) plaque deposition, Tau pathology and dysfunction of the cholinergic system causing memory impairment. The aim of the present study was to examine (1) anxiety and cognition, (2) Abeta plaque deposition and (3) degeneration of cholinergic neurons in the nucleus basalis of Meynert (nbM) and cortical cholinergic innervation in an Alzheimer mouse model (APP_SweDI; overexpressing amyloid precursor protein (APP) with the Swedish K670N/M671L, Dutch E693Q, and Iowa D694N mutations). Our results show that 12 month-old APP_SweDI mice were more anxious and had more memory impairment. A large number of Abeta plaques were already visible at the age of 6 months and increased with age. A significant decrease in cholinergic neurons was seen in the transgenic mouse model in comparison to the wild-type mice, identified by immunohistochemistry against choline acetyltransferase (ChAT) and p75 neurotrophin receptor as well as by in situ hybridization. Moreover, a significant decrease in cortical cholinergic fiber density was found in the transgenic mice as compared to the wild-type. In the cerebral cortex of APP_SweDI mice, swollen cholinergic varicosities were seen in the vicinity of Abeta plaques. In conclusion, the present study shows that in an AD mouse model (APP_SweDI mice) a high Abeta plaque load in the cortex causes damage to cholinergic axons in the cortex, followed by subsequent retrograde-induced cell death of cholinergic neurons and some forms of compensatory processes. This degeneration was accompanied by enhanced anxiety and impaired cognition. PMID- 27670618 TI - An update on focal therapy for prostate cancer. AB - Globally, the increased uptake of serum PSA level screening led to an increase in the number of diagnoses of low-risk and intermediate-risk prostate cancer. Traditionally, these patients have been considered for either active surveillance programmes or radical whole-gland therapies, such as prostatectomy or radiotherapy. Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue. This approach might result in reduced morbidity when compared with whole gland therapies. In current practice, much controversy surrounds optimal patient selection and preoperative tumour localization strategies. Focal therapy modalities include cryotherapy, high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, radiofrequency ablation and focal brachytherapy. However, as long-term oncological data for focal therapies are lacking, formal recommendations for its use cannot be made. PMID- 27670621 TI - Management of Severely Subluxated Cataracts Using Femtosecond Laser-Assisted Cataract Surgery. AB - PURPOSE: To assess the role of femtosecond laser technology in the management of severely subluxated cataracts. DESIGN: Retrospective, interventional case series. METHODS: All eyes with subluxated cataract seen between July 2012 and June 2015 were assessed for suitability for femtosecond laser-assisted cataract surgery, with the use of capsular tension devices. Participants with subluxated cataracts of at least 6 clock hours of zonular weakness were included in the study. Data collected included patient demographics, preoperative and postoperative best corrected visual acuity (BCVA), nuclear density, extent of zonular weakness, completeness of capsulotomy, and complications. Poor visual outcome was defined as BCVA of worse than 20/40. Main outcome measure was the retention of the capsular bag. RESULTS: Of the 72 eyes with subluxated cataracts undergoing surgery during the study period, 47 eyes of 47 patients were eligible for analysis. Mean age of the patients was 60.7 years (standard deviation [SD] 13.2 years). The majority were male (32, 68.1%) and Chinese (38, 80.8%). The mean duration of follow-up was 8 months (SD 5.6 months). The main identifiable cause of lens subluxation was trauma (11 eyes). Almost two thirds (30 eyes) had more than 9 clock hours of zonular weakness. Seventy percent of cataracts (33) were nuclear sclerosis grade 3 and above. The capsular bag was preserved in 43 eyes (91.5%). The intraocular lens was stable and centered at the last follow-up in all these 43 eyes. An anterior capsule tear occurred in 6 eyes, all of which had cataracts of nuclear sclerosis grade 3 and above, with posterior extension occurring in 3 eyes. Primary posterior capsule rupture occurred in 1 eye. At 1 month 37 eyes (80.4%) had a BCVA of 20/40 or better. There was significant improvement in BCVA at 1 month (mean of 0.92 logMAR units [SD 0.88] to 0.22 [SD 0.38] [P < .001, paired samples t test]), which was maintained at 1 year. CONCLUSIONS: Selected cases of severely subluxated cataracts may be managed using femtosecond laser technology to perform the capsulotomy and nuclear fragmentation, with successful preservation of the capsular bag in 90% of eligible cases, especially in eyes with soft cataracts. PMID- 27670622 TI - Endoscopic Transnasal Removal of Cavernous Hemangiomas of the Optic Canal. AB - PURPOSE: To assess the feasibility and efficacy of endoscopic transnasal removal of cavernous hemangiomas of the optic canal. DESIGN: Retrospective, noncomparative case series. METHODS: Eleven consecutive patients (11 eyes) with cavernous hemangioma of the optic canal underwent endoscopic trans-ethmoidal sphenoidal removal of the tumor at the Eye Hospital of Wenzhou Medical University from January 2009 to March 2016. In each case, the indication for surgery was decreased visual acuity due to the tumor. The removal was believed to be complete if the tumor was removed en bloc during the surgery. A mucoperiosteal flap was used to cover the defect in the optic nerve sheath after tumor removal. The tumor was pathologically confirmed to be cavernous hemangioma after surgery. The mean follow-up time was 9.9 +/- 5.5 months. Visual acuity before and after surgery was compared. RESULTS: All tumors were completely removed by the endoscopic approach. The best-corrected visual acuity (BCVA) improved after surgery in all patients. The mean preoperative BCVA was 6/30 (95% confidence interval [CI] 6/60-6/20) and the mean postoperative BCVA was 6/10 (95% CI 6/12-6/7.5). All patients showed cerebrospinal fluid rhinorrhea, which resolved with strict bed rest. Other complications included hyposmia in 2 patients; nasal bleeding in 3 patients, which resolved spontaneously; and temporary headache. CONCLUSIONS: Endoscopic trans-ethmoidal-sphenoidal approach is a feasible option for cavernous hemangiomas of the optic canal. PMID- 27670623 TI - The microbial epigenome in metabolic syndrome. AB - Dietary habits, lifestyle, medication, and food additives affect the composition and functions of the GI microbiota. Metabolic syndrome is already known to be associated with an aberrant gut microbiota affecting systemic low-grade inflammation, which is also outlined by differing epigenetic patterns. Thus, structural changes and compositional evaluation of gut microbial differences affecting epigenetic patterns in metabolic syndrome are of research interest. In the present review we focus on the disparities in the gut microbiota composition of metabolic syndrome and the resulting aberrant profile of bioactive microbial metabolites known to affect epigenetic modifications such as G-protein coupled receptors and inflammatory pathways. PMID- 27670624 TI - Perikymata distribution on anterior teeth of Miocene Lufengpithecus lufengensis from Yunnan, Southern China. AB - OBJECTIVES: The present study investigated the distribution of perikymata on anterior teeth of Miocene Lufengpithecus lufengensis so as to broaden the comparative data of developmental variation within and among hominoids. We also compared perikymata-spacing pattern of Lufengpithecus lufengensis with hominins and extant African great apes to understand the implication of dental development. MATERIALS AND METHODS: A total of 30 anterior teeth (including 6 I1, 10 I2, and 14 C) of Lufengpithecus lufengensis were examined using a scanning electron microscope and Keyence VHX-600EOS digital microscope to document the number and distribution of perikymata on their labial surfaces. The labial crown height of each tooth was divided into 10 equal deciles and the total perikymata number in each decile was recorded. The mean number of perikymata per millimeter was then calculated for each decile. SPSS statistical software was used to perform analyses of these data, including t-tests for sexual dimorphism and plots showing the perikymata distribution in Lufengpithecus lufengensis. RESULTS: Perikymata counts of Lufengpithecus lufengensis in the first three deciles are fewer than the remaining deciles, and with perikymata becoming increasingly more closely packed as growth progresses from cusp to cervix, but decrease in density in the cervical decile. Besides, total labial perikymata counts of canines tend to display very significant sexual dimorphism. DISCUSSION: Lufengpithecus lufengensis anterior teeth are more similar in their distribution of labial perikymata to those of Australopithecus than those of other hominins and extant African great apes from previous studies. PMID- 27670625 TI - Intense conductivity suppression by edge defects in zigzag MoS2 and WSe2 nanoribbons: a density functional based tight-binding study. AB - The effects of edge vacancies on the electron transport properties of zigzag MoS2/WSe2 nanoribbons are studied using a density functional theory (DFT)-based tight-binding model with a sp(3)d(5) basis set for the electronic structure calculation and applying the Landauer-Buttiker approach for the electronic transport. Our results show that the presence of a single edge vacancy, with a missing MoS2/WSe2 triplet, is enough to suppress the conductance of the system by almost one half for most energies around the Fermi level. Furthermore, the presence of other single defects along the same edge has little effect on the overall conductance, indicating that the conductance of that particular edge has been strongly suppressed by the first defect. The presence of another defect on the opposite edge further suppresses the quantum conductance, independently of the relative position between the two defects in opposite edges. The introduction of other defects cause the suppression to be energy dependent, leading to conductance peaks which depend on the geometry of the edges. The strong conductance dependence on the presence of edge defects is corroborated by DFT calculations using SIESTA, which show that the electronic bands near the Fermi energy are strongly localized at the edge. PMID- 27670626 TI - Medical education of attention: A qualitative study of learning to listen to sound. AB - INTRODUCTION: There has been little qualitative research examining how physical examination skills are learned, particularly the sensory and subjective aspects of learning. The authors set out to study how medical students are taught and learn the skills of listening to sound. METHODS: As part of an ethnographic study in Melbourne, 15 semi-structured in-depth interviews were conducted with students and teachers as a way to reflect explicitly on their learning and teaching. RESULTS: From these interviews, we found that learning the skills of listening to lung sounds was frequently difficult for students, with many experiencing awkwardness, uncertainty, pressure, and intimidation. However not everyone found this process difficult. Often those who had studied music reported finding it easier to be attentive to the frequency and rhythm of body sounds and find ways to describe them. CONCLUSIONS: By incorporating, distinctively in medical education, theoretical insights into "attentiveness" from anthropology and science and technology studies, the article suggests that musical education provides medical students with skills in sensory awareness. Training the senses is a critical aspect of diagnosis that needs to be better addressed in medical education. Practical approaches for improving students' education of attention are proposed. PMID- 27670627 TI - Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram. AB - BACKGROUND: Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE: The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS: We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 +/- 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS: In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 +/- 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION: SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone. PMID- 27670629 TI - Reply to the Editor- Novel Method for Earlier Detection of Phrenic Nerve Injury During Cryoballoon Applications for Electrical Isolation of Pulmonary Veins in Patients With Atrial Fibrillation. PMID- 27670628 TI - Regional distribution of T-tubule density in left and right atria in dogs. AB - BACKGROUND: The peculiarities of transverse tubule (T-tubule) morphology and distribution in the atrium-and how they contribute to excitation-contraction coupling-are just beginning to be understood. OBJECTIVES: The objectives of this study were to determine T-tubule density in the intact, live right and left atria in a large animal and to determine intraregional differences in T-tubule organization within each atrium. METHODS: Using confocal microscopy, T-tubules were imaged in both atria in intact, Langendorf-perfused normal dog hearts loaded with di-4-ANEPPS. T-tubules were imaged in large populations of myocytes from the endocardial surface of each atrium. Computerized data analysis was performed using a new MatLab (Mathworks, Natick, MA) routine, AutoTT. RESULTS: There was a large percentage of myocytes that had no T-tubules in both atria with a higher percentage in the right atrium (25.1%) than in the left atrium (12.5%) (P < .02). The density of transverse and longitudinal T-tubule elements was low in cells that did contain T-tubules, but there were no significant differences in density between the left atrial appendage, the pulmonary vein-posterior left atrium, the right atrial appendage, and the right atrial free wall. In contrast, there were significant differences in sarcomere spacing and cell width between different regions of the atria. CONCLUSION: There is a sparse T-tubule network in atrial myocytes throughout both dog atria, with significant numbers of myocytes in both atria-the right atrium more so than the left atrium-having no T-tubules at all. These regional differences in T-tubule distribution, along with differences in cell width and sarcomere spacing, may have implications for the emergence of substrate for atrial fibrillation. PMID- 27670630 TI - Further evidence that remote monitoring is cost-effective: It's time for all to adopt. PMID- 27670631 TI - Fragmentation and defragmenting: How to ablate in the age of connectivity? PMID- 27670632 TI - Evolution of MRI abnormalities in paediatric acute disseminated encephalomyelitis. AB - OBJECTIVE: Acute disseminating encephalomyelitis (ADEM) is an inflammatory demyelinating disease affecting the central nervous system and mainly occurs in young children. Children who initially presented with ADEM can be diagnosed with multiple sclerosis (MS) in case new non-encephalopathic clinical symptoms occur with new lesions on MRI at least three months after onset of ADEM. We aim to study the timing of MRI abnormalities related to the evolution of clinical symptoms in our Dutch paediatric ADEM cohort. METHODS: The Dutch database for acquired demyelinating syndromes (ADS) was screened for children under age eighteen fulfilling the international consensus diagnostic criteria for ADEM. Children were eligible when the first MRI was performed within the first three months after onset of clinical symptoms and at least one brain follow-up MRI was available for evaluation. Forty-two children with ADEM were included (median age four years two months). All available MRIs and medical records were assessed and categorised as 'improved', 'deteriorated' and 'unchanged'. RESULTS: We found that during clinical recovery, new lesions and enlargement of existing MRI lesions occurred in the first three months in about 50% of the performed MRIs. In contrast, this was rarely seen more than three months after first onset of ADEM. CONCLUSION: We recommend to perform a brain MRI as a reference scan three months after onset. Follow-up imaging should be compared with this scan in order to prevent an incorrect diagnosis of MS after ADEM. PMID- 27670634 TI - Inhibitory effects of Japanese horseradish (Wasabia japonica) on the formation and genotoxicity of a potent carcinogen, acrylamide. AB - BACKGROUND: The formation of acrylamide (AA) in cooked foods has raised human health concerns. AA is metabolized by cytochrome P450 2E1 (CYP2E1) to glycidamide (GA), which forms DNA adducts. This study examined the inhibitory effects of wasabi (Japanese horseradish, Wasabia japonica) roots and leaves as well as their active component, allyl isothiocyanate (AIT), on the formation and genotoxicity of AA. RESULTS: AA formation (51.8 +/- 4.2 ug kg-1 ) was inhibited with >=2 mg mL 1 of AIT. Wasabi roots also inhibited AA formation (~90% reduction), but wasabi leaves were not effective at 2 mg mL-1 . Wasabi roots and leaves decreased the number of cells with micronuclei by approximately 33 and 24% respectively compared with the AA treatment group. Moreover, wasabi roots and leaves (100 mg kg-1 body weight (BW) day-1 for each) decreased AA (100 mg kg-1 BW day-1 ) induced DNA damage. The AA-induced CYP2E1 activity was decreased by 39 and 26% with wasabi roots and leaves respectively. Further, the activity of glutathione S transferase, which catalyzes the detoxification of AA via glutathione conjugation, increased by 54 and 33% with wasabi roots and leaves respectively. CONCLUSION: These results indicate that wasabi roots and leaves are effective ingredients for inhibiting the formation and genotoxicity of AA. (c) 2016 Society of Chemical Industry. PMID- 27670635 TI - Benchmarking Measures of Network Influence. AB - Identifying key agents for the transmission of diseases (ideas, technology, etc.) across social networks has predominantly relied on measures of centrality on a static base network or a temporally flattened graph of agent interactions. Various measures have been proposed as the best trackers of influence, such as degree centrality, betweenness, and k-shell, depending on the structure of the connectivity. We consider SIR and SIS propagation dynamics on a temporally extruded network of observed interactions and measure the conditional marginal spread as the change in the magnitude of the infection given the removal of each agent at each time: its temporal knockout (TKO) score. We argue that this TKO score is an effective benchmark measure for evaluating the accuracy of other, often more practical, measures of influence. We find that none of the network measures applied to the induced flat graphs are accurate predictors of network propagation influence on the systems studied; however, temporal networks and the TKO measure provide the requisite targets for the search for effective predictive measures. PMID- 27670633 TI - Evaluation of non-Gaussian diffusion in cardiac MRI. AB - PURPOSE: The diffusion tensor model assumes Gaussian diffusion and is widely applied in cardiac diffusion MRI. However, diffusion in biological tissue deviates from a Gaussian profile as a result of hindrance and restriction from cell and tissue microstructure, and may be quantified better by non-Gaussian modeling. The aim of this study was to investigate non-Gaussian diffusion in healthy and hypertrophic hearts. METHODS: Thirteen rat hearts (five healthy, four sham, four hypertrophic) were imaged ex vivo. Diffusion-weighted images were acquired at b-values up to 10,000 s/mm2 . Models of diffusion were fit to the data and ranked based on the Akaike information criterion. RESULTS: The diffusion tensor was ranked best at b-values up to 2000 s/mm2 but reflected the signal poorly in the high b-value regime, in which the best model was a non-Gaussian "beta distribution" model. Although there was considerable overlap in apparent diffusivities between the healthy, sham, and hypertrophic hearts, diffusion kurtosis and skewness in the hypertrophic hearts were more than 20% higher in the sheetlet and sheetlet-normal directions. CONCLUSION: Non-Gaussian diffusion models have a higher sensitivity for the detection of hypertrophy compared with the Gaussian model. In particular, diffusion kurtosis may serve as a useful biomarker for characterization of disease and remodeling in the heart. Magn Reson Med 78:1174-1186, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27670636 TI - Mitochondria-Associated Membranes Response to Nutrient Availability and Role in Metabolic Diseases. AB - Metabolic diseases are associated with nutrient excess and metabolic inflexibility. Mitochondria and endoplasmic reticulum are important organelles and nutrient sensors, and their dysfunction has been extensively and independently implicated in metabolic diseases. Both organelles interact at sites known as mitochondria-associated membranes (MAMs), in order to exchange metabolites and calcium. Recent evidence indicates that MAM could be a hub of hepatic insulin signaling and nutrient sensing. In this review, we discuss the roles organelle function and communication play in the cell's adaptation to nutrient availability, in both physiology and metabolic diseases. We highlight how dynamic regulation of MAM affects mitochondria physiology and adaptation of cellular metabolism to nutrient availability, and how chronic MAM disruption participates in the metabolic inflexibility associated with metabolic disorders. PMID- 27670638 TI - Quantifying full phenological event distributions reveals simultaneous advances, temporal stability and delays in spring and autumn migration timing in long distance migratory birds. AB - Phenological changes in key seasonally expressed life-history traits occurring across periods of climatic and environmental change can cause temporal mismatches between interacting species, and thereby impact population and community dynamics. However, studies quantifying long-term phenological changes have commonly only measured variation occurring in spring, measured as the first or mean dates on which focal traits or events were observed. Few studies have considered seasonally paired events spanning spring and autumn or tested the key assumption that single convenient metrics accurately capture entire event distributions. We used 60 years (1955-2014) of daily bird migration census data from Fair Isle, Scotland, to comprehensively quantify the degree to which the full distributions of spring and autumn migration timing of 13 species of long distance migratory bird changed across a period of substantial climatic and environmental change. In most species, mean spring and autumn migration dates changed little. However, the early migration phase (<=10th percentile date) commonly got earlier, while the late migration phase (>=90th percentile date) commonly got later. Consequently, species' total migration durations typically lengthened across years. Spring and autumn migration phenologies were not consistently correlated within or between years within species and hence were not tightly coupled. Furthermore, different metrics quantifying different aspects of migration phenology within seasons were not strongly cross-correlated, meaning that no single metric adequately described the full pattern of phenological change. These analyses therefore reveal complex patterns of simultaneous advancement, temporal stability and delay in spring and autumn migration phenologies, altering species' life-history structures. Additionally, they demonstrate that this complexity is only revealed if multiple metrics encompassing entire seasonal event distributions, rather than single metrics, are used to quantify phenological change. Existing evidence of long-term phenological changes detected using only one or two metrics should consequently be interpreted cautiously because divergent changes occurring simultaneously could potentially have remained undetected. PMID- 27670637 TI - A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research. AB - BACKGROUND: The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). METHODS: A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. RECOMMENDATIONS: A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. CONCLUSION: The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings. PMID- 27670639 TI - Fixed-dose combination of nifedipine gastrointestinal therapeutic system and candesartan cilexetil in patients with moderate-to-severe essential hypertension: an open-label, long-term safety and efficacy study. AB - WHAT IS KNOWN AND OBJECTIVE: The nifedipine gastrointestinal therapeutic system (GITS)/candesartan cilexetil (N/C) combination was demonstrated to be an effective, well-tolerated antihypertensive therapy in a short-term study. The current study investigated the long-term safety and efficacy of a fixed-dose combination (FDC) of N/C therapy in moderate-to-severe essential hypertension. METHODS: A multinational, 70-centre, open-label study of N/C treatment for 28 or 52 weeks at a target dose of N60 mg/C32 mg. The primary assessment included the incidence of treatment-emergent adverse events (TEAEs). Efficacy assessments included change from baseline in systolic and diastolic blood pressure (BP). RESULTS AND DISCUSSION: A total of 508 patients were enrolled, with 417 (82.1%) completing week 28 of treatment. Of these, 200 patients continued treatment, as planned, to week 52, with 193 (96.5%) completing this period. At least one TEAE or drug-related TEAE were reported in 76.8% and 45.3% patients up to week 28, and in 80.7% and 46.9% up to week 52/end of study. Most TEAEs and drug-related TEAEs to week 52 (93.9% and 95.4%, respectively) were mild or moderate in intensity. Rates of drug-related serious AEs were low (0.6%). TEAE-related discontinuations occurred in 10% patients before week 28 and in no additional patients thereafter. N/C provided substantial, sustained reductions in mean systolic and diastolic BP from baseline: 30.1 +/- 18.4 and 12.8 +/- 10.7 mmHg, respectively, at week 52. WHAT IS NEW AND CONCLUSIONS: Nifedipine GITS/candesartan cilexetil FDC at the target dose of 60 mg/32 mg was well tolerated for a study duration up to 52 weeks and provided sustained reductions in systolic and diastolic BP. PMID- 27670640 TI - Bone morphogenetic protein-4 modulates proliferation and terminal differentiation of fetal hepatic stem/progenitor cells. AB - : Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver organogenesis; however, molecular mechanisms regulating proliferation and terminal differentiation of such cells have not been completely elucidated. Bone morphogenetic protein-4 (BMP-4) is essential for the development of stem cells in various tissues, but its function in regulating the phenotype of hepatoblasts after the mid-gestational fetal stage remains unclear. The aim of this study is to clarify a functional role for BMP-4 in proliferation and terminal differentiation of murine hepatoblasts in mid-gestational fetal livers. METHODS: A functional role for BMP-4 in proliferation and terminal differentiation of murine hepatoblasts was validated by assay of colony formation, biliary luminal formation, and hepatic maturation using primary hepatoblasts in vitro. Molecular mechanisms regulating such effects of BMP-4 on primary hepatoblasts were also analyzed. RESULTS: Stimulation of BMP-4 upregulated phosphorylation of Smad1/5 in hepatoblasts. Bone morphogenetic protein-4 significantly suppressed colony formation of primary hepatoblasts in a dose-dependent manner, significantly suppressed cholangiocytic luminal formation of hepatoblasts, and promoted hepatic maturation of primary hepatoblasts. Stimulation of BMP-4 regulated the activation of several mitogen-activated protein kinases, such as extracellular signal regulated kinase, Akt, p38 mitogen-activated protein kinase, and calcium/calmodulin-dependent protein kinase IIalpha in primary hepatoblasts. Moreover, Wnt5a, a molecule regulating cholangiocytic luminal formation, and BMP 4 coordinately suppressed proliferation and cholangiocytic luminal formation of hepatoblasts. CONCLUSION: This study shows that BMP-4-mediated signaling controls proliferation and terminal differentiation of fetal hepatic stem/progenitor cells. PMID- 27670641 TI - Torpor-responsive expression of novel microRNA regulating metabolism and other cellular pathways in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus. AB - Research has demonstrated the importance of microRNA in cold-tolerant animals, including their dynamic regulation throughout mammalian hibernation. In this study, we used small RNA sequencing and bioinformatic methods to identify novel microRNA regulating gene expression during hibernation in thirteen-lined ground squirrels, Ictidomys tridecemlineatus. A group of 17 novel microRNA was identified, and their relative expression was quantitated using real-time quantitative polymerase chain reaction in liver, skeletal muscle, and heart tissues over four experimental conditions that represent the torpor-arousal cycle. Predicted mRNA targets of these novel microRNA were found to be enriched in biological processes known to be regulated during hibernation, such as lipid metabolism, ion-transport ATPases, and various cellular signaling cascades. This study provides an analysis of several novel microRNA that may be crucial to adaptation during hibernation. PMID- 27670642 TI - Extranodal Rosai-Dorfman Disease of the Breast. PMID- 27670643 TI - HydDB: A web tool for hydrogenase classification and analysis. AB - H2 metabolism is proposed to be the most ancient and diverse mechanism of energy conservation. The metalloenzymes mediating this metabolism, hydrogenases, are encoded by over 60 microbial phyla and are present in all major ecosystems. We developed a classification system and web tool, HydDB, for the structural and functional analysis of these enzymes. We show that hydrogenase function can be predicted by primary sequence alone using an expanded classification scheme (comprising 29 [NiFe], 8 [FeFe], and 1 [Fe] hydrogenase classes) that defines 11 new classes with distinct biological functions. Using this scheme, we built a web tool that rapidly and reliably classifies hydrogenase primary sequences using a combination of k-nearest neighbors' algorithms and CDD referencing. Demonstrating its capacity, the tool reliably predicted hydrogenase content and function in 12 newly-sequenced bacteria, archaea, and eukaryotes. HydDB provides the capacity to browse the amino acid sequences of 3248 annotated hydrogenase catalytic subunits and also contains a detailed repository of physiological, biochemical, and structural information about the 38 hydrogenase classes defined here. The database and classifier are freely and publicly available at http://services.birc.au.dk/hyddb/. PMID- 27670645 TI - Simultaneous quantification of triterpenoid saponins in rat plasma by UHPLC-MS/MS and its application to a pharmacokinetic study after oral total saponin of Aralia elata leaves. AB - A rapid, sensitive, and reliable analytical ultra performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of Aralia-saponin IV, 3-O-beta-d-glucopyranosyl-(1->3) beta-d-glucopyranosyl-(1->3)-beta-d-glucopyranosyl oleanolic acid 28-O-beta-d glucopyranoside, Aralia-saponin A and Aralia-saponin B after the oral administration of total saponin of Aralia elata leaves in rat plasma. Plasma samples were pretreated by protein precipitation with methanol. The analysis was performed on an ACQUITY UPLC HSS T3 column. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source with negative ionization mode. Under the experimental conditions, the calibration curves of four analytes had good linearity values (r > 0.991). The intra- and inter-day precision values of the four analytes were <= 11.6%, and the accuracy was between -6.2 and 4.2%.The extraction recoveries of four triterpenoid saponins were in the range of 84.06 91.66% (RSD < 10.5%), and all values of the matrix effect were more than 90.30%. The developed analytical method was successfully applied to pharmacokinetic study on simultaneous determination of the four triterpenoid saponins in rat plasma after oral administration of total saponin of Aralia elata leaves, which helps guiding clinical usage of Aralia elata leaves. PMID- 27670644 TI - Reduction in cardiometabolic risk factors by a multifunctional diet is mediated via several branches of metabolism as evidenced by nontargeted metabolite profiling approach. AB - SCOPE: Multifunctional diet (MFD), a diet based on multiple functional concepts and ingredients with anti-inflammatory activity, was previously shown to improve different cardiometabolic risk-associated markers in healthy subjects. Here, we assessed the impact of MFD on plasma metabolome and explored associations of the differential metabolites with clinical parameters, searching for metabolic determinants related to the effects of MFD. METHODS AND RESULTS: Forty-four overweight healthy volunteers completed a randomized crossover intervention comparing MFD with a control diet devoid of the active components of MFD. Fasting plasma samples were analyzed with nontargeted metabolite profiling at baseline and at the end (4 wk) of each diet period by LC coupled to quadrupole-TOF-MS system, revealing a vast impact of MFD on metabolic homeostasis. Main metabolite classes affected included acylcarnitines, furan fatty acids, phospholipids (plasmalogens, phosphatidylcholines, phosphatidylethanolamines), and various low molecular weight products from the bioactivity of gut microbiota. Circulating levels of several of these metabolites correlated with changes in clinical blood lipid biomarkers. CONCLUSIONS: The metabolomics approach revealed that consumption of MFD affected different areas of metabolism, highlighting the impact of a healthy diet on plasma metabolome. This seems linked to reduced cardiometabolic risk and provides mechanistic insight into the effects of MFD. PMID- 27670646 TI - Whole-body angular momentum during sloped walking using passive and powered lower limb prostheses. AB - Sloped walking requires altered strategies for maintaining dynamic balance relative to level-ground walking, as evidenced by changes in sagittal-plane whole body angular momentum (H) in able-bodied individuals. The ankle plantarflexor muscles are critical for regulating H, and functional loss of these muscles from transtibial amputation affects this regulation. However, it is unclear if a powered prosthesis, which more closely emulates intact ankle function than a passive energy-storage-and-return prosthesis, affects H differently during sloped walking. Therefore, our purpose was to investigate H in individuals with unilateral transtibial amputation when using powered and passive prostheses. Overall, the range of H was greater in people with a transtibial amputation relative to able-bodied individuals. On a -10 degrees decline, individuals with amputation did not decrease H as much as able-bodied individuals, and had reduced prosthetic limb braking ground reaction forces and knee power absorption. On a +10 degrees incline, individuals with amputation had a greater relative increase of H than able-bodied individuals, a more anterior placement of the prosthetic foot, and higher peak hip power generation. The powered prosthesis condition resulted in a smaller range of H during prosthetic stance relative to the passive condition, although it was still larger than able-bodied individuals. Our results suggest that prosthetic ankle power generation may help regulate dynamic balance during prosthetic stance, but alone is not sufficient for restoring H to that of able-bodied individuals on slopes. Contributions of knee extensor muscles and the biarticular gastrocnemius in regulating H on slopes should be further investigated. PMID- 27670647 TI - Community perspectives: evaluation of a community-based rehabilitation program in Southern Belize one year post-implementation. AB - PURPOSE: To examine community perspectives regarding the strengths, weaknesses, opportunities, and threats of a community-based rehabilitation (CBR) program in Toledo District, Belize. METHOD: A participatory approach was implemented using the CBR Matrix as a conceptual framework. Semi-structured interviews were conducted with CBR community partners and program participants living in Toledo District. Respondents were recruited until thematic saturation was achieved (i.e., no new themes were identified from subsequent interviews). Interviews were recorded and transcribed verbatim. Recurring themes were identified using thematic content analysis. RESULTS: Eight CBR community partners and 11 program participants completed interviews. Key strengths of the program included engaging CBR program participants as partners in the decision-making process and raising disability awareness. Key weaknesses of the program included lack of a vocational training program and lack of a systematic approach to identify people with disabilities (PWD) or risk factors for disease and disability. CONCLUSIONS: This participatory evaluation provided PWD, their families, and the community the opportunity to express their needs and priorities regarding CBR. Key recommendations included: (1) developing vocational training programs for PWD; (2) expanding collaborations with craftspeople and other community partners throughout Toledo District; (3) continuing the disability awareness program in schools and the broader community; and (4) strengthening community outreach and data collection. Implications for Rehabilitation Persons with disabilities, their families, and community partners should play an active role in the development, implementation, and evaluation of CBR programs to ensure program goals align with community priorities. The CBR evaluation process should strive to include diverse perspectives that represent the most marginalized populations (e.g., individuals with significant disabilities living in geographically remote areas). The CBR matrix can provide a comprehensive and flexible framework with which to examine community perspectives regarding the strengths, weaknesses, opportunities, and threats of CBR programs. PMID- 27670648 TI - An Automated Microwell Platform for Large-Scale Single Cell RNA-Seq. AB - Recent developments have enabled rapid, inexpensive RNA sequencing of thousands of individual cells from a single specimen, raising the possibility of unbiased and comprehensive expression profiling from complex tissues. Microwell arrays are a particularly attractive microfluidic platform for single cell analysis due to their scalability, cell capture efficiency, and compatibility with imaging. We report an automated microwell array platform for single cell RNA-Seq with significantly improved performance over previous implementations. We demonstrate cell capture efficiencies of >50%, compatibility with commercially available barcoded mRNA capture beads, and parallel expression profiling from thousands of individual cells. We evaluate the level of cross-contamination in our platform by both tracking fluorescent cell lysate in sealed microwells and with a human-mouse mixed species RNA-Seq experiment. Finally, we apply our system to comprehensively assess heterogeneity in gene expression of patient-derived glioma neurospheres and uncover subpopulations similar to those observed in human glioma tissue. PMID- 27670649 TI - Esophageal bougination: a novel ex vivo endoscopic training model correlated with clinical data. AB - BACKGROUND: Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against. PATIENTS AND METHODS: A three step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting. RESULTS: With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model. DISCUSSION: The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary. PMID- 27670650 TI - [Management of systemic lupus erythematosus]. AB - In the last few decades a number of small, often largely unrecognized steps have fundamentally changed the management of systemic lupus erythematosus (SLE). The current goal is to stop all disease activity without long-term use of more than 5 mg prednisolone per day. Remission, i.e. absence of activity in the SLE activity score of choice, is the defined target in the treat to target approach. The essential basic measures include life-long hydroxychloroquine as well as protection from sunlight (UV) and vitamin D substitution. Patients suffering from SLE need more vaccinations than the healthy population and control of risk factors for atherosclerosis is critical for long-term survival. Methotrexate is on par with azathioprine. If disease activity cannot be controlled in this way, belimumab is an approved therapeutic option. Cyclophosphamide is still used but only in life-threatening situations, such as lupus nephritis or central nervous system (CNS) vasculitis and in drastically reduced doses. Alternatively, off label mycophenolate mofetil (MMF) can be used particularly for lupus nephritis and off-label rituximab in refractory disease courses. Numerous novel approaches are being tested in controlled trials and it is hoped that new drugs will be available for SLE patients within a few years. PMID- 27670652 TI - Wearable fitness device does not help maintain weight loss, study finds. PMID- 27670651 TI - Predictors of pain during oocyte retrieval. AB - INTRODUCTION: Pain during oocyte retrieval remains prevalent despite detailed and specific pain management protocols. Exploring the role of psychosocial risk factors of pain during the oocyte retrieval could identify possible targets for prevention. The present study assessed pain prevalence and possible risk factors for experiencing extreme pain levels in a large cohort of women receiving assisted reproductive technologies (ART) treatment. METHODS: Participants were 810 first attendees about to begin treatment with ART. The participants completed questionnaires at three time points: at their 21st day of the cycle, during the waiting time before the oocyte retrieval surgery and after the oocyte retrieval. RESULTS: Fifty-one (6.9%) of the women reported the oocyte retrieval to be very or extremely painful. The results of a multiple logistic regression indicated that the significant predictors of high pain intensity, measured before the oocyte retrieval, were negative gynecological experiences and side effects of hormonal treatment. Variables measured after the oocyte retrieval associated with pain intensity were higher levels of anxiety during the oocyte retrieval, lower levels of perceived control and longer duration of the procedure. DISCUSSION: The findings of the present study may help to identify those women who are at increased risk of experiencing unacceptable pain levels during oocyte retrieval procedures and the medical staff is advised to take psychological factors into account. PMID- 27670654 TI - Water uptake mechanism and germination of Erythrina velutina seeds treated with atmospheric plasma. AB - The effect of plasma applied to mulungu (Erythrina velutina) seeds was studied to verify its influence on the germination, water absorption, wettability and structure of the seeds. The plasma jet used in this study was produced by dielectric barrier discharge (DBD) in a helium gas flow of 0.03 L/s at a distance of 13 mm for 60 s. The plasma treatment significantly affected the seed germination rate, which was approximately 5% higher than that of the untreated group. Micropyle and hilum contributed a greater proportion to uptake. When sealed in the hilar or micropyle regions the amount of water absorbed into the seed decreased approximately 75% compared to the unsealed seed. This difference suggests that these two regions together act cooperatively in the water absorption. However, when plasma treated seed was blocked in the micropyle region, water absorption was higher higher than in seeds blocked hilum. This difference suggests that the plasma treatment changed the wettability of the hilum more effectively than it changed the micropyle. These results indicate that plasma can significantly change the hydrophilicity, water absorption and percentage of seed germination in E. velutina. PMID- 27670653 TI - Amputation trends for patients with lower extremity ulcers due to diabetes and peripheral artery disease using statewide data. AB - OBJECTIVE: This study reports all-payer amputation rates using state-based administrative claims data for high-risk patients with lower extremity (LE) ulcers and concomitant peripheral artery disease (PAD), diabetes mellitus (DM), or combination PAD/DM. In addition, we characterize patient factors that affect amputation-free survival. We also attempted to create a measure of a patient's ability to manage chronic diseases or to access appropriate outpatient care for ulcer management by accounting for hospital and emergency department (ED) visits in the preceding 60 days to determine how this also affects amputation-free survival. METHODS: Patients admitted to nonfederal hospitals, seen in an ED, or treated in an eligible ambulatory surgery center within California from 2005 through 2013 with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a disease-specific LE ulcer were identified in the California Office of Statewide Health Planning and Development database. All subsequent hospital, ED, and ambulatory surgery center visits and procedures are captured to identify whether a patient underwent major amputation. Yearly amputation rates were determined to analyze trends. Amputation-free survival for the PAD, DM, and PAD/DM groups was determined. Cox modeling was used to evaluate the effect of patient characteristics. RESULTS: There were 219,547 patients identified with an incident LE ulcer throughout the state. Of these, 131,731 were DM associated, 36,193 were PAD associated, and 51,623 were associated with both PAD and DM. From 2005 to 2013, the number of patients with LE ulcers who required inpatient admission, presented to the ED, or had outpatient procedures was stable. However, there was a statistically significant increase in overall disease-associated amputation rates from 5.1 in 2005 to 13.5 in 2013 (P < .001). Patients with PAD/DM had the greatest increase in amputation rates from 10 per 100 patients with LE ulcers in 2005 to 28 per 100 patients in 2013 (P < .001). Despite that patients with PAD/DM were 8 years younger than patients with PAD only, they had similar amputation-free survival. Within all age groups, men had worse amputation-free survival than women did. Race did not predict amputation-free survival, but having multiple prior ED or hospital admissions was a significant predictor of worse amputation-free survival. CONCLUSIONS: Potentially preventable amputations associated with high-risk diseases are increasing among patients who require inpatient hospital admission, present to the ED, or require outpatient interventional treatment. This trend is most notable among patients with a combination of PAD and DM. Patients with repeated hospitalizations before admission for the LE ulcer had the highest risk of amputation. PMID- 27670655 TI - Healthier lifestyles after retirement in Europe? Evidence from SHARE. AB - This paper investigates changes in health behaviours upon retirement, using data drawn from the Survey of Health Ageing and Retirement in Europe. By exploiting changes in eligibility rules for early and statutory retirement, we identify the causal effect of retiring from work on smoking, alcohol drinking, engagement in physical activity and visits to the general practitioner or specialist. We provide evidence about individual heterogeneous effects related to gender, education, net wealth, early-life conditions and job characteristics. Our main results--obtained using fixed-effect two-stage least squares--show that changes in health behaviours occur upon retirement and may be a key mechanism through which the latter affects health. In particular, the probability of not practicing any physical activity decreases significantly after retirement, and this effect is stronger for individuals with higher education. We also find that different frameworks of European health care systems (i.e. countries with or without a gate keeping system to regulate the access to specialist services) matter in shaping individuals' health behaviours after retirement. Our findings provide important information for the design of policies aiming to promote healthy lifestyles in later life, by identifying those who are potential target individuals and which factors may affect their behaviour. Our results also suggest the importance of policies promoting healthy lifestyles well before the end of the working life in order to anticipate the benefits deriving from individuals' health investments. PMID- 27670658 TI - Is It Time to Separate the Financial and Health Goals of Workplace Health Promotion Programs? PMID- 27670659 TI - The Art of Health Promotion ideas for improving health outcomes. PMID- 27670656 TI - Procedural safety of a fully implantable intravenous prostanoid pump for pulmonary hypertension. AB - BACKGROUND: In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension. METHODS: All patients with pulmonary hypertension undergoing pump implantation for the continuous application of intravenous treprostinil were included from two German centers. Surgery was performed under local or general anesthesia according to the protocol of the recruiting center. Intra-operative safety and in-hospital complications were analyzed for the two different implantation regimens. RESULTS: In total, 51 patients were included. No major intra-operative complications were recorded. During the observation period, two patients died of progressive right heart failure, and two patients required treatment in the intensive care unit for acute right heart decompensation and respiratory failure. In total, major complications occurred in 8 out of 51 patients. CONCLUSIONS: Our observational study provides preliminary evidence supporting the procedural safety of a fully implantable pump inserted under local or general anesthesia for patients with severe pulmonary hypertension. The observation of major complications in a subset of patients requires extensive pre- and post-operative assessments. Future trials are required to provide further evidence for the long-term safety and efficacy of the pump using this approach. PMID- 27670660 TI - Interpretations of diffusion-weighted MR imaging by radiology residents in the emergency department: is diagnostic performance influenced by the level of residency training? AB - BACKGROUND: To evaluate the diagnostic performance of radiology residents' interpretations for diffusion-weighted MR imaging (DWI) in the emergency department at different levels of residency training. METHOD AND MATERIALS: A total of 160 patients who underwent DWI with acute neurologic symptoms were included in this retrospective study with an institutional review board approval. Four radiology residents with different training years and one attending neuroradiologist independently assessed the DWI results. Discordances between the results of residents and attending neuroradiologist were classified as follows: false positive (FP) and false negative (FN). We also evaluated the diagnostic performance of four residents according to the reference standard. RESULTS: Overall, the concordance rate was 84.8 %, with a 15.2 % overall discordance rate. There were 83 FN results. The most common misses were small vessel disease (n = 55), acute focal infarction (n = 10), diffuse axonal injury (n = 6), solitary mass (n = 5), extraaxial hemorrhages (n = 3), posterior reversible encephalopathy syndrome (n = 2), and postictal change (n = 2). Fourteen FP results were interpreted as hemorrhage and acute infarction. The 4th year resident exhibited the highest diagnostic performance, and the level of training had a significant influence on the rates of concordance (P < 0.05). Interobserver reliability was good between the interpretations of the residents and the final interpretations of the attending neuroradiologists. CONCLUSION: The level of resident training had a significant effect on their diagnostic performance, and good interobserver reliability was noted between the results of the residents and attending neuroradiologist. PMID- 27670662 TI - Your Understanding Is My Understanding: Evidence for a Community of Knowledge. AB - In four experiments, we tested the community-of-knowledge hypothesis, that people fail to distinguish their own knowledge from other people's knowledge. In all the experiments, despite the absence of any actual explanatory information, people rated their own understanding of novel natural phenomena as higher when they were told that scientists understood the phenomena than when they were told that scientists did not yet understand them. In Experiment 2, we found that this occurs only when people have ostensible access to the scientists' explanations; the effect does not occur when the explanations exist but are held in secret. In Experiment 3, we further ruled out two classes of alternative explanations (one appealing to task demands and the other proposing that judgments were mediated by inferences about a phenomenon's understandability). In Experiment 4, we ruled out the possibility that the effect could be attributed to a pragmatic inference. PMID- 27670661 TI - Role of TRPC1 channels in pressure-mediated activation of murine pancreatic stellate cells. AB - The tumor environment contributes importantly to tumor cell behavior and cancer progression. Aside from biochemical constituents, physical factors of the environment also influence the tumor. Growing evidence suggests that mechanics [e.g., tumor (stroma) elasticity, tissue pressure] are critical players of cancer progression. Underlying mechanobiological mechanisms involve among others the regulation of focal adhesion molecules, cytoskeletal modifications, and mechanosensitive (MS) ion channels of cancer- and tumor-associated cells. After reviewing the current concepts of cancer mechanobiology, we will focus on the canonical transient receptor potential 1 (TRPC1) channel and its role in mechano signaling in tumor-associated pancreatic stellate cells (PSCs). PSCs are key players of pancreatic fibrosis, especially in cases of pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by the formation of a dense fibrotic stroma (desmoplasia), primarily formed by activated PSCs. Desmoplasia contributes to high pancreatic tissue pressure, which in turn activates PSCs, thereby perpetuating matrix deposition. Here, we investigated the role of the putatively mechanosensitive TRPC1 channels in murine PSCs exposed to elevated ambient pressure. Pressurization leads to inhibition of mRNA expression of MS ion channels. Migration of PSCs representing a readout of their activation is enhanced in pressurized PSCs. Knockout of TRPC1 leads to an attenuated phenotype. While TRPC1-mediated calcium influx is increased in wild-type PSCs after pressure incubation, loss of TRPC1 abolishes this effect. Our findings provide mechanistic insight how pressure, an important factor of the PDAC environment, contributes to PSC activation. TRPC1-mediated activation could be a potential target to disrupt the positive feedback of PSC activation and PDAC progression. PMID- 27670663 TI - Emotions in "Black and White" or Shades of Gray? How We Think About Emotion Shapes Our Perception and Neural Representation of Emotion. AB - The demands of social life often require categorically judging whether someone's continuously varying facial movements express "calm" or "fear," or whether one's fluctuating internal states mean one feels "good" or "bad." In two studies, we asked whether this kind of categorical, "black and white," thinking can shape the perception and neural representation of emotion. Using psychometric and neuroimaging methods, we found that (a) across participants, judging emotions using a categorical, "black and white" scale relative to judging emotions using a continuous, "shades of gray," scale shifted subjective emotion perception thresholds; (b) these shifts corresponded with activity in brain regions previously associated with affective responding (i.e., the amygdala and ventral anterior insula); and (c) connectivity of these regions with the medial prefrontal cortex correlated with the magnitude of categorization-related shifts. These findings suggest that categorical thinking about emotions may actively shape the perception and neural representation of the emotions in question. PMID- 27670665 TI - Sensitivity of Scenedesmus obliquus and Microcystis aeruginosa to atrazine: effects of acclimation and mixed cultures, and their removal ability. AB - Atrazine is an herbicide frequently detected in watercourses that can affect the phytoplankton community, thus impacting the whole food chain. This study aims, firstly, to measure the sensitivity of monocultures of the green alga Scenedemus obliquus and toxic and non-toxic strains of the cyanobacteria Microcystis aeruginosa before, during and after a 30-day acclimation period to 0.1 uM of atrazine. Secondly, the sensitivity of S. obliquus and M. aeruginosa to atrazine in mixed cultures was evaluated. Finally, the ability of these strains to remove atrazine from the media was measured. We demonstrated that both strains of M. aeruginosa had higher growth rate-based EC50 values than S. obliquus when exposed to atrazine, even though their photosynthesis-based EC50 values were lower. After being exposed to 0.1 uM of atrazine for 1 month, only the photosynthesis-based EC50 of S. obliquus increased significantly. In mixed cultures, the growth rate of the non-toxic strain of M. aeruginosa was higher than S. obliquus at high concentrations of atrazine, resulting in a ratio of M. aeruginosa to total cell count of 0.6. This lower sensitivity might be related to the higher growth rate of cyanobacteria at low light intensity. Finally, a negligible fraction of atrazine was removed from the culture media by S. obliquus or M. aeruginosa over 6 days. These results bring new insights on the acclimation of some phytoplankton species to atrazine and its effect on the competition between S. obliquus and M. aeruginosa in mixed cultures. PMID- 27670664 TI - Understanding the Influence of Mental Health Diagnosis and Gender on Placement Decisions for Justice-Involved Youth. AB - Justice-involved youth have high rates of psychiatric diagnoses, and these youth are often placed out-of-home, although evidence identifies several negative implications of juvenile confinement, especially for youth with psychopathology. Furthermore, youth in the justice system may be processed differently based on gender. As males and females tend to manifest symptoms differently, the psychopathology of youth may act to moderate the relationship between gender and placement in the juvenile justice system. The present study used a large, diverse sample (n = 9 851, 19.8 % female) to examine whether youth placed in various types of out-of-home facilities differed in terms of externalizing, internalizing, substance use, or comorbid disorders, and to determine the predictive value of mental health diagnoses in placement decisions. The moderation effect of psychopathology and substance use on the relationship between gender and placement also was explored. The results indicated that each type of disorder differed across placements, with internalizing being most prevalent in non-secure, and externalizing, comorbid, and substance use being most prevalent in secure settings. Mental health diagnoses improved the prediction of placement in each out-of-home placement beyond legal and demographic factors such that externalizing and substance use disorders decreased the likelihood of placement in non-secure settings, and internalizing, externalizing, and substance use disorders increased the likelihood of placement in secure and state-secure facilities. The relationship between internalizing pathology and placement in more secure facilities was moderated by externalizing pathology. The relationship between gender and placement was significantly moderated by mental health such that females with mental health diagnoses receive less secure placements. Implications for policymakers and practitioners are discussed, as well as implications for reforming juvenile justice within a developmental approach. PMID- 27670667 TI - Congo red dye affects survival and reproduction in the cladoceran Ceriodaphnia dubia. Effects of direct and dietary exposure. AB - Nearly 7 00000 tons of dyes are produced annually throughout the world. Azo dyes are widely used in the textile and paper industries due to their low cost and ease of application. Their extensive use results in large volumes of wastewater being discharged into aquatic ecosystems. Large volume discharges constitute a health risk since many of these dyes, such as Congo Red, are elaborated with benzidine, a known carcinogenic compound. Information regarding dye toxicity in aquatic ecosystems is limited. Therefore, the aim of the present study was to evaluate the effect of Congo Red on survival and reproduction of Ceriodaphnia dubia. We determined the 48 h median lethal concentration (LC50) and evaluated the effects of sublethal concentrations in subchronic exposures by using as food either fresh algae or algae previously exposed to the dye. LC50 was 13.58 mg L-1. In subchronic assays, survival was reduced to 80 and 55 %, and fertility to 40 and 70 %, as compared to the control, in C. dubia fed with intoxicated cells or with the mix of intoxicated + fresh algae, respectively, so the quantity and type of food had a significant effect. We determined that Congo Red is highly toxic to C. dubia since it inhibits survival and fertility in concentrations exceeding 3 mg L-1. Our results show that this dye produces negative effects at very low concentrations. Furthermore, our findings warn of the risk associated with discharging dyes into aquatic environments. Lastly, the results emphasize the need to regulate the discharge of effluents containing azo dyes. PMID- 27670666 TI - Sublethal effects of imidacloprid on the predatory seven-spot ladybird beetle Coccinella septempunctata. AB - The seven-spot ladybird beetle, Coccinella septempunctata, is a major natural enemy of aphids in the field and in greenhouses in China and is part of integrated pest management (IPM). Imidacloprid, a highly efficient insecticide that not only kills aphids at lethal concentrations, but also can cause various sublethal effects in nontarget organisms. To strengthen IPM and its sustainability, it is important assessing possible side effects on natural enemies. When the effects of sublethal concentrations (LC5 and 10%LC5) of imidacloprid on C. septempunctata were evaluated, the adult longevity was shortened by 23.97 and 28.68 %, and the fecundity reduced by 52.81 and 56.09 % compared to control population. In the F1 generation (i.e., the progeny of the exposed individuals), the juvenile development was slower by 1.44 days and 0.66 days, and the oviposition period was shortened by 10 and 13 days, respectively. The fecundity of the F1 generation decreased by 17.88, 44.03 and 51.69 % when exposed to 1%LC5, 10%LC5, and LC5, respectively. The results of demographical growth estimates showed that the intrinsic rate of increase (r m ) and net reproductive rate (R 0 ) were lower in C. septempunctata populations that had been exposed to sublethal concentrations of imidacloprid. The results emphasize the importance of assessing side effects of low imidacloprid concentrations on such predator species, even at the transgenerational level. PMID- 27670669 TI - (+/-)-Gossypol induces apoptosis and autophagy in head and neck carcinoma cell lines and inhibits the growth of transplanted salivary gland cancer cells in BALB/c mice. AB - Racemic Gossypol [(+/-)-GOS], composed of both (-)-GOS and (+)-GOS, is a small BH3-mimetic polyphenol derived from cotton seeds. (+/-)-GOS has been employed and well tolerated by cancer patients. Head and neck carcinoma (HNC) represents one of the most fatal cancers worldwide, and a significant proportion of HNC expresses high levels of antiapoptotic Bcl-2 proteins. In this study, we demonstrate that (+/-)-GOS inhibits cell proliferation and induces apoptosis and autophagy of human pharynx, tongue, and salivary gland cancer cell lines and of mouse salivary gland cancer cells (SALTO). (+/-)-GOS was able to: (a) decrease the ErbB2 protein expression; (b) inhibit the phosphorylation of ERK1/2 and AKT; (c) stimulate p38 and JNK1/2 protein phosphorylation. (+/-)-GOS administration was safe in BALB/c mice and it reduced the growth of transplanted SALTO cells in vivo and prolonged mice median survival. Our results suggest the potential role of (+/-)-GOS as an antitumor agent in HNC patients. PMID- 27670668 TI - Sublethal and transgenerational effects of sulfoxaflor on the biological traits of the cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae). AB - Sulfoxaflor is a novel insecticide belonging to sulfoximine chemical class that can be used to control sap-feeding insects, notably Aphis gossypii Glover. In addition to its acute toxicity, it is also important to consider the possible sublethal effects when establishing a comprehensive understanding of the toxicity of a new insecticide. We assessed the effects of a low lethal concentration (LC25) of sulfoxaflor on biological parameters of A. gossypii adults (F0) and subsequent transgenerational effects, i.e., on the progeny (F1 generation). The data were analyzed using an age-stage life table procedure. The results showed that the longevity and fecundity were not significantly affected by the LC25 of sulfoxaflor in the F0 or F1 generations. In addition, no significant differences were observed on the developmental time of each instar, the adult pre-oviposition period, and on the longevity of F1 individuals. However, the duration of their pre-adult stage and total pre-oviposition period, as well as their mean generation time were significantly increased. These observed effects affected aphid demographic traits; the survival rate, the intrinsic rate of increase (r i ), the finite rate of increase (lambda), the net reproductive rate (R0), and the gross reproduction rate (GRR) of the F1 individuals (i.e., from F0 mothers) were significantly lower compared to the control. Our results showed that sublethal effects of sulfoxaflor significantly slowed down A. gossypii population growth; they indicated that effects of sulfoxaflor might be increased (beyond lethal effect) through sublethal effects when concentrations decreased in sulfoxaflor treated areas after initial application in field. PMID- 27670670 TI - Lesion strength control by automatic temperature guided retinal photocoagulation. AB - Laser photocoagulation is an established treatment for a variety of retinal diseases. However, when using the same irradiation parameter, the size and strength of the lesions are unpredictable due to unknown inter- and intraindividual optical properties of the fundus layers. The aim of this work is to investigate a feedback system to generate desired lesions of preselectable strengths by automatically controlling the irradiation time. Optoacoustics were used for retinal temperature monitoring. A 532-nm continuous wave Nd:YAG laser was used for photocoagulation. A 75-ns/523-nm Q-switched Nd:YLF laser simultaneously excited temperature-dependent pressure transients, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. The temperature data were analyzed during the irradiation by a LabVIEW routine. The treatment laser was switched off automatically when the required lesion strength was achieved. Five different feedback control algorithms for different lesion sizes were developed and tested on rabbits in vivo. With a laser spot diameter of 133???m, five different lesion types with ophthalmoscopically visible diameters ranging mostly between 100 and 200???m, and different appearances were achieved by automatic exposure time control. The automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation. PMID- 27670671 TI - It's Not Easy Not Being Green: Breakthroughs in Chlorophyll Breakdown. PMID- 27670673 TI - Animal choruses emerge from receiver psychology. AB - Synchrony and alternation in large animal choruses are often viewed as adaptations by which cooperating males increase their attractiveness to females or evade predators. Alternatively, these seemingly composed productions may simply emerge by default from the receiver psychology of mate choice. This second, emergent property hypothesis has been inferred from findings that females in various acoustic species ignore male calls that follow a neighbor's by a brief interval, that males often adjust the timing of their call rhythm and reduce the incidence of ineffective, following calls, and from simulations modeling the collective outcome of male adjustments. However, the purported connection between male song timing and female preference has never been tested experimentally, and the emergent property hypothesis has remained speculative. Studying a distinctive katydid species genetically structured as isolated populations, we conducted a comparative phylogenetic analysis of the correlation between male call timing and female preference. We report that across 17 sampled populations male adjustments match the interval over which females prefer leading calls; moreover, this correlation holds after correction for phylogenetic signal. Our study is the first demonstration that male adjustments coevolved with female preferences and thereby confirms the critical link in the emergent property model of chorus evolution. PMID- 27670672 TI - Identification of LATE BLOOMER2 as a CYCLING DOF FACTOR Homolog Reveals Conserved and Divergent Features of the Flowering Response to Photoperiod in Pea. AB - The molecular pathways responsible for the flowering response to photoperiod have been extensively studied in Arabidopsis thaliana and cereals but remain poorly understood in other major plant groups. Here, we describe a dominant mutant at the LATE BLOOMER2 (LATE2) locus in pea (Pisum sativum) that is late-flowering with a reduced response to photoperiod. LATE2 acts downstream of light signaling and the circadian clock to control expression of the main photoperiod-regulated FT gene, FTb2, implying that it plays a primary role in photoperiod measurement. Mapping identified the CYCLING DOF FACTOR gene CDFc1 as a strong candidate for LATE2, and the late2-1D mutant was found to carry a missense mutation in CDFc1 that impairs its capacity to bind to the blue-light photoreceptor FKF1 in yeast two-hybrid assays and delays flowering in Arabidopsis when overexpressed. Arabidopsis CDF genes are important negative regulators of CONSTANS (CO) transcription, but we found no effect of LATE2 on the transcription of pea CO LIKE genes, nor on genes in any other families previously implicated in the activation of FT in Arabidopsis. Our results reveal an important component of the pea photoperiod response pathway and support the view that regulation of FTb2 expression by photoperiod occurs via a CO-independent mechanism. PMID- 27670674 TI - Development of a ReaxFF Reactive Force Field for the Pt-Ni Alloy Catalyst. AB - We developed the ReaxFF force field for Pt/Ni/C/H/O interactions, specifically targeted for heterogeneous catalysis application of the Pt-Ni alloy. The force field is trained using the DFT data for equations of state of Pt3Ni, PtNi3 and PtNi alloys, the surface energy of the PtxNi1-x(111) (x = 0.67-0.83), and binding energies of various atomic and molecular species (O, H, C, CH, CH2, CH3, CO, OH, and H2O) on these surfaces. The ReaxFF force field shows a Pt surface segregation at x >= 0.67 for the (111) surface and x >= 0.62 for the (100) surface in vacuum. In addition, from the investigation of the preferential alloy component of the adsorbates, it is expected that H and CH3 on the alloy surface to induce a segregation of Pt whereas the oxidation intermediates and products such as C, O, OH, H2O, CO, CH, and CH2 are found to induce Ni segregation. The relative order of binding strengths among adsorbates is a function of alloy composition and the force field is trained to describe the trend observed in DFT calculations, namely, H2 < H2O < CH3 ~ O2 ~ CO < OH < CH2 < C ~ CH on Pt8Ni4, H2 < H2O < CO < O2 ~ CH3 < OH < CH2 < CH < C on Pt9Ni3, and H2 < H2O < O2 < CO < CH3 < OH < CH2 < C ~ CH on Pt10Ni2. Using this force field, we performed the grand-canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulations for a Pt3Ni slab and a truncated cuboctahedral nanoparticle terminated by (111) and (100) faces, to examine the surface segregation trend under different gas environments. It is found that Pt segregates to the alloy surface when the surface is exposed to vacuum and/or H2 environment while Ni segregates under the O2 environment. These results suggest that the Pt/Ni alloy force field can be successfully used for the preparation of Pt-Ni nanobimetallic catalysts structure using GCMC and run MD simulations to investigate its role and the catalytic chemistry in catalytic oxidation, dehydrogenation and coupling reactions. The current Pt/Ni force field still is found to have difficulties in describing the observed segregation trend in Ni-rich alloy compositions (x < 0.6), suggesting the need for additional force field training and evaluation for its application to describe the characteristics and chemistry of Ni-rich alloys. PMID- 27670675 TI - Individual patients are the primary source and the target of clinical research. PMID- 27670676 TI - Following international trends while subject to past traditions: neuropsychological test use in the Nordic countries. AB - OBJECTIVE: Historically, the neuropsychological test traditions of the four Nordic countries have spanned from the flexible and qualitative tradition of Luria-Christensen to the quantitative large battery approach of Halstead and Klove-Matthews. This study reports current test use and discusses whether these traditions still influence attitudes toward test use and choice of tests. METHOD: The study is based on survey data from 702 Nordic neuropsychologists. RESULTS: The average participant used 9 tests in a standard assessment, and 25 tests overall in their practice. Test use was moderated by nationality, competence level, practice profile, and by attitude toward test selection. Participants who chose their tests flexibly used fewer tests than those adhering to the flexible battery approach, but had fewer tests from which to choose. Testing patients with psychiatric disorders was associated with using more tests. IQ, memory, attention, and executive function were the domains with the largest utilization rate, while tests of motor, visual/spatial, and language were used by few. There is a lack of academic achievement tests. Screening tests played a minor role in specialized assessments, and symptom validity tests were seldom applied on a standard basis. Most tests were of Anglo-American origin. CONCLUSIONS: New test methods are implemented rapidly in the Nordic countries, but test selection is also characterized by the dominating position of established and much researched tests. The Halstead-Reitan and Luria traditions are currently weak, but national differences in size of test batteries seem to be influenced by these longstanding traditions. PMID- 27670678 TI - Successful treatment of multidrug-resistant Pseudomonas aeruginosa breakthrough bacteremia with ceftolozane/tazobactam. AB - INTRODUCTION: Ceftolozane/tazobactam is a novel antibiotic approved for the treatment of complicated intra-abdominal and complicated urinary tract infections. CASE DESCRIPTION: We describe the use of off-label ceftolozane/tazobactam in the management of a multidrug-resistant Pseudomonas aeruginosa bacteremia that was already being treated with colistin and amikacin, the only active antibiotics according to the antibiogram. PMID- 27670677 TI - 14-3-3zeta regulates the mitochondrial respiratory reserve linked to platelet phosphatidylserine exposure and procoagulant function. AB - The 14-3-3 family of adaptor proteins regulate diverse cellular functions including cell proliferation, metabolism, adhesion and apoptosis. Platelets express numerous 14-3-3 isoforms, including 14-3-3zeta, which has previously been implicated in regulating GPIbalpha function. Here we show an important role for 14-3-3zeta in regulating arterial thrombosis. Interestingly, this thrombosis defect is not related to alterations in von Willebrand factor (VWF)-GPIb adhesive function or platelet activation, but instead associated with reduced platelet phosphatidylserine (PS) exposure and procoagulant function. Decreased PS exposure in 14-3-3zeta-deficient platelets is associated with more sustained levels of metabolic ATP and increased mitochondrial respiratory reserve, independent of alterations in cytosolic calcium flux. Reduced platelet PS exposure in 14-3-3zeta deficient mice does not increase bleeding risk, but results in decreased thrombin generation and protection from pulmonary embolism, leading to prolonged survival. Our studies define an important role for 14-3-3zeta in regulating platelet bioenergetics, leading to decreased platelet PS exposure and procoagulant function. PMID- 27670679 TI - Tuberculous spondylitis diagnosed through Xpert MTB/RIF assay in urine: a case report. AB - BACKGROUND: Extrapulmonary tuberculosis (EPTB) is associated with high rates of morbidity and mortality. Diagnosis of EPTB is challenging in resource-limited settings due to difficulties in obtaining samples, as well as the paucibacillarity of the specimens. Skeletal tuberculosis accounts for 10-35 % of EPTB cases, with vertebral osteomyelitis (Pott's disease) representing 50 % of the cases. We present two cases of suspected Pott's disease, diagnosed through GeneXpert MTB/RIF assay in urine at a rural Tanzanian hospital. CASE PRESENTATION: Case I A 49-year old male, HIV-1 positive, on co-formulated tenofovir disoproxil fumarate/lamivudine/efavirenz since 2009 and CD4 counts of 205 cells/MUL (13 %). He presented with lower back pain and progressive lower limb weakness for two weeks prior to admission. The physical examination revealed bilateral flaccid paraplegia with reduced reflexes, but otherwise unremarkable findings. A lateral lumbar X-ray showed noticeable reduction of intervertebral space between L4 and L5, and a small calcification in the anterior longitudinal ligament between L4 and L5, being compatible with focal spondylosis deformans but inconclusive with regard to tuberculous spondylitis. An abdominal ultrasound showed normal kidneys, bladder and prostate gland. The urinalysis and complete blood counts (CBC) were normal. M. Tuberculosis was detected through GeneXpert MTB/RIF in centrifuged urine, with no resistance to rifampicin. Case II A 76-year old female, HIV-1 negative, presented with lower back pain and progressive weakness and numbness of the lower limbs for two months prior to admission. The physical examination revealed paraplegia, but otherwise unremarkable findings. The lumbosacral X-ray findings were compatible with spondylosis deformans of the lumbar spine and possible tuberculous spondylitis in L3-L4. The abdominal and renal ultrasound showed normal kidneys and bladder. The urinalysis and CBC were normal. M. Tuberculosis was detected through GeneXpert MTB/RIF in centrifuged urine, with no resistance to rifampicin. CONCLUSION: We report two cases of suspected tuberculous spondylitis diagnosed through Xpert MTB/RIF in urine samples from a rural Tanzanian hospital. Urine testing using Xpert MTB/RIF reflects disseminated disease and renal involvement, and may offer a feasible additional diagnostic approach for Pott's disease in rural Africa. PMID- 27670681 TI - Anti-cancer activity of Psoralea fructus through the downregulation of cyclin D1 and CDK4 in human colorectal cancer cells. AB - BACKGROUND: Psoralea Fructus (PF), the dried and ripe fruit of Psoralea corylifolia exhibits an anti-cancer activity. However, the molecular mechanisms by which PF inhibits the proliferation of cancer cells have not been elucidated in detail. Cyclin D1 and CDK4 are important regulatory proteins in cell growth and are overexpressed in many cancer cells. In this study, we investigated the molecular mechanism of PF on the downregulation of cyclin D1 and CDK4 level. METHODS: Cell growth was evaluated by MTT assay. The effect of PF on cyclin D1 and CDK4 expression was evaluated by Western blot or RT-PCR. RESULTS: PF suppressed the proliferation of human colorectal cancer cell lines such as HCT116 (IC50: 45.3 +/- 1.2 MUg/ml), SW480 (IC50: 37.9 +/- 1.6 MUg/ml), LoVo (IC50: 23.3 +/- 1.9 MUg/ml MUg/ml) HT-29 (IC50 value: 40.7 +/- 1.5 MUg/ml). PF induced decrease in the protein expression of cyclin D1 and CDK4. However, the mRNA expression of cyclin D1 and CDK4 did not be changed by PF; rather it suppressed the expression of cyclin D1 and CDK4 via the proteasomal degradation. In cyclin D1 degradation, we found that T286 of cyclin D1 play a pivotal role in PF mediated cyclin D1 degradation. Subsequent experiments with several kinase inhibitors suggest that PF-mediated degradation of cyclin D1 and CDK4 is dependent on ERK1/2 and/or GSK3beta. CONCLUSIONS: Our results suggest that PF has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. PMID- 27670680 TI - Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors. AB - BACKGROUND: HIV-1 typically develops resistance to any single antiretroviral agent. Combined anti-retroviral therapy to reduce drug-resistance development is necessary to control HIV-1 infection. Here, to assess the utility of a combination of antibody and fusion inhibitor treatments, we investigated the potency of monoclonal antibodies at neutralizing HIV-1 variants that are resistant to fusion inhibitors. RESULTS: Mutations that confer resistance to four fusion inhibitors, enfuvirtide, C34, SC34, and SC34EK, were introduced into the envelope of HIV-1JR-FL, a CCR5-tropic tier 2 strain. Pseudoviruses with these mutations were prepared and used for the assessment of neutralization sensitivity to an array of antibodies. The resulting neutralization data indicate that the potencies of some antibodies, especially of those against the CD4 binding site, V3 loop, and membrane-proximal external region epitopes, were increased by the mutations in gp41 that conferred resistance to the fusion inhibitors. C34-, SC34 , and SC34EK-resistant mutants showed more sensitivity to monoclonal antibodies than enfuvirtide-resistant mutants. An analysis of C34-resistant mutations revealed that the I37K mutation in gp41 HR1 is a key mutation for C34 resistance, low infectivity, neutralization sensitivity, epitope exposure, and slow fusion kinetics. The N126K mutation in the gp41 HR2 domain contributed to C34 resistance and neutralization sensitivity to anti-CD4 binding site antibodies. In the absence of L204I, the effect of N126K was antagonistic to that of I37K. The results of a molecular dynamic simulation of the envelope trimer confirmation suggest that an I37K mutation induces the augmentation of structural fluctuations prominently in the interface between gp41 and gp120. Our observations indicate that the "conformational unmasking" of envelope glycoprotein by an I37K mutation is one of the mechanisms of neutralization sensitivity enhancement. Furthermore, the enhanced neutralization of C34-resistant mutants in vivo was shown by its high rate of neutralization by IgG from HIV patient samples. CONCLUSIONS: Mutations in gp41 that confer fusion inhibitor resistance exert enhanced sensitivity to broad neutralizing antibodies (e.g., VRC01 and 10E8) and other conventional antibodies developed in HIV-1 infected patients. Therefore, next generation fusion inhibitors and monoclonal antibodies could be a potential combination for future regimens of combined antiretroviral therapy. PMID- 27670682 TI - The impact of automating laboratory request forms on the quality of healthcare services. AB - In recent decades, healthcare organizations have undergone a significant transformation with the integration of Information and Communication Technologies within healthcare operations to improve healthcare services. Various technologies such as Hospital Information Systems (HIS), Electronic Health Records (EHR) and Laboratory Information Systems (LIS) have been incorporated into healthcare services. The aim of this study is to evaluate the completeness of outpatients' laboratory paper based request forms in comparison with a electronic laboratory request system. This study was carried out in the laboratory department at King Abdulaziz Medical City (KAMC), National Guard Health Affairs, Riyadh, Saudi Arabia. We used a sample size calculator for comparing two proportions. We estimated the sample size to be 228 for each group. Any laboratory requests including paper and electronic forms were included. We categorized the clarity of the forms into understandable, readable, and unclear. A total of 57 incomplete paper forms or 25% were identified as being incomplete. For electronic forms, there were no incomplete fields, as all fields were mandatory, therefore, rendering them complete. The total of understandable paper-based laboratory forms was 11.4%. Additionally, it was found that the total of readable was 33.8% and the total for unclear was 54.8%, while for electronic-based forms, there were no unclear forms. Electronic based laboratory forms provide a more complete, accurate, clear, and understandable format than paper-based laboratory records. Based on these findings, KAMC should move toward the implementation of electronic based laboratory request forms for the outpatient laboratory department. PMID- 27670683 TI - Definition and management of varicella zoster virus-associated meningoradiculitis: a case report. AB - BACKGROUND: The varicella zoster virus affects the central or peripheral nervous systems upon reactivation, especially when cell-mediated immunity is impaired. Among varicella zoster virus-related neurological syndromes, meningoradiculitis is an ill-defined condition for which clear management guidelines are still lacking. Zoster paresis is usually considered to be a varicella zoster virus peripheral nervous system complication and treated with oral antiviral therapy. Yet in the literature, the few reported cases of herpes zoster with mild cerebral spinal fluid inflammation were all considered meningoradiculitis and treated using intravenous antiviral drugs, despite absence of systemic signs of meningitis. Nevertheless, these two clinical pictures are very similar. CASE PRESENTATION: We report the case of an alcohol-dependent elderly Caucasian man presenting with left lower limb zoster paresis and mild cerebral spinal fluid inflammation, with favorable outcome upon IV antiviral treatment. We discuss interpretation of liquor inflammation in the absence of clinical meningitis and implications for the antiviral treatment route. CONCLUSION: From this case report we suggest that varicella zoster virus-associated meningoradiculitis should necessarily include meningitis symptoms with the peripheral neurological deficits and cerebral spinal fluid inflammation, requiring intravenous antiviral treatment. In the absence of (cell-mediated) immunosuppression, isolated zoster paresis does not necessitate spinal tap or intravenous antiviral therapy. PMID- 27670684 TI - Red Blood Cell Distribution Width in Patients With Chronic Obstructive Pulmonary Disease and Healthy Subjects. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease (CVD). Red blood cell distribution width (RDW) is accepted as a powerful predictor of outcomes in patients with CVD. AIMS: To study RDW in patients with COPD, and to compare the value of this measurement with clinical, echocardiographic, nutritional and laboratory status. Secondly, we aimed to determine the effect of smoking on RDW values in healthy subjects. METHODS: One hundred and seventy-five patients with stable COPD and 210 healthy controls were enrolled in the study. Demographic, clinical, nutritional status, echocardiographic, and laboratory characteristics, RDW values were recorded and compared. RESULTS: RDW values were higher in the COPD group than in controls (15+/-2.3% vs. 13.8+/-2.5%, p<0.001). In COPD patients, RDW levels positively correlated with CRP levels (r=0.27, P<.001), albumin levels (r=0.23, P=.04), right ventricular dysfunction (RVD) (r=0.24, P=.001), pulmonary hypertension (PAH) (r=0.1, P=.02), and presence of CVD (r=0.24, P=.02). In multivariable logistic regression suggested that presence of CVD (4.3; 95% CI: 1.3 to 11; P=.01), and presence of RVD (3.1; 95% CI: 1.7 to 8.3; P=.02) were independently related to elevated RDW levels in COPD patients. In the healthy population, correlations analysis showed only a significant correlation between RDW and cigarette smoking years (r=0.57, P<.001). CONCLUSION: RDW is independently associated with CVD and RVD in patients with COPD. In the healthy population, RDW is also associated with smoking status. PMID- 27670685 TI - Acquisition of natural humoral immunity to P. falciparum in early life in Benin: impact of clinical, environmental and host factors. AB - To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas.Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6-to18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6-to18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life. PMID- 27670686 TI - Magnetoresponsive Poly(ether sulfone)-Based Iron Oxide cum Hydrogel Mixed Matrix Composite Membranes for Switchable Molecular Sieving. AB - Stimuli-responsive membranes that can adjust mass transfer and interfacial properties "on demand" have drawn large interest over the last few decades. Here, we designed and prepared a novel magnetoresponsive separation membrane with remote switchable molecular sieving effect by simple one-step and scalable nonsolvent induced phase separation (NIPS) process. Specifically, poly(ether sulfone) (PES) as matrix for an anisotropic membrane, prefabricated poly(N isopropylacrylamide) (PNIPAAm) nanogel (NG) particles as functional gates, and iron oxide magnetic nanoparticles (MNP) as localized heaters were combined in a synergistic way. Before membrane casting, the properties of the building blocks, including swelling property and size distribution for NG, and magnetic property and heating efficiency for MNP, were investigated. Further, to identify optimal film casting conditions for membrane preparation by NIPS, in-depth rheological study of the effects of composition and temperature on blend dope solutions was performed. At last, a composite membrane with 10% MNP and 10% NG blended in a porous PES matrix was obtained, which showed a large, reversible, and stable magneto-responsivity. It had 9 times higher water permeability at the "on" state of alternating magnetic field (AMF) than at the "off"-state. Moreover, the molecular weight cutoff of such membrane could be reversibly shifted from ~70 to 1750 kDa by switching off or on the external AMF, as demonstrated in dextran ultrafiltration tests. Overall, it has been proved that the molecular sieving performance of the novel mixed matrix composite membrane can be controlled by the swollen/shrunken state of PNIPAAm NG embedded in the nanoporous barrier layer of a PES-based anisotropic porous matrix, via the heat generation of nearby MNP. And the structure of such membrane can be tailored by the NIPS process conditions. Such membrane has potential as enabling material for remote-controlled drug release systems or devices for tunable fractionations of biomacromolecule/ particle mixtures. PMID- 27670689 TI - NoisyGOA: Noisy GO annotations prediction using taxonomic and semantic similarity. AB - Gene Ontology (GO) provides GO annotations (GOA) that associate gene products with GO terms that summarize their cellular, molecular and functional aspects in the context of biological pathways. GO Consortium (GOC) resorts to various quality assurances to ensure the correctness of annotations. Due to resources limitations, only a small portion of annotations are manually added/checked by GO curators, and a large portion of available annotations are computationally inferred. While computationally inferred annotations provide greater coverage of known genes, they may also introduce annotation errors (noise) that could mislead the interpretation of the gene functions and their roles in cellular and biological processes. In this paper, we investigate how to identify noisy annotations, a rarely addressed problem, and propose a novel approach called NoisyGOA. NoisyGOA first measures taxonomic similarity between ontological terms using the GO hierarchy and semantic similarity between genes. Next, it leverages the taxonomic similarity and semantic similarity to predict noisy annotations. We compare NoisyGOA with other alternative methods on identifying noisy annotations under different simulated cases of noisy annotations, and on archived GO annotations. NoisyGOA achieved higher accuracy than other alternative methods in comparison. These results demonstrated both taxonomic similarity and semantic similarity contribute to the identification of noisy annotations. Our study shows that annotation errors are predictable and removing noisy annotations improves the performance of gene function prediction. This study can prompt the community to study methods for removing inaccurate annotations, a critical step for annotating gene and pathway functions. PMID- 27670688 TI - Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry. AB - Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. PMID- 27670687 TI - Peripheral quantitative computed tomography (pQCT) for the assessment of bone strength in most of bone affecting conditions in developmental age: a review. AB - Peripheral quantitative computed tomography provides an automatical scan analysis of trabecular and cortical bone compartments, calculating not only their bone mineral density (BMD), but also bone geometrical parameters, such as marrow and cortical Cross-Sectional Area (CSA), Cortical Thickness (CoTh), both periosteal and endosteal circumference, as well as biomechanical parameters like Cross Sectional Moment of Inertia (CSMI), a measure of bending, polar moment of inertia, indicating bone strength in torsion, and Strength Strain Index (SSI). Also CSA of muscle and fat can be extracted. Muscles, which are thought to stimulate bones to adapt their geometry and mineral content, are determinant to preserve or increase bone strength; thus, pQCT provides an evaluation of the functional 'muscle-bone unit', defined as BMC/muscle CSA ratio. This functional approach to bone densitometry can establish if bone strength is normally adapted to the muscle force, and if muscle force is adequate for body size, providing more detailed insights to targeted strategies for the prevention and treatment of bone fragility. The present paper offers an extensive review of technical features of pQCT and its possible clinical application in the diagnostic of bone status as well as in the monitoring of the skeleton's health follow-up. PMID- 27670690 TI - DNA methylation is not involved in specific down-regulation of HSD3B2, NR4A1 and RARB genes in androgen-secreting cells of human adrenal cortex. AB - We hypothesized that DNA methylation is involved in human adrenal functional zonation. mRNAs expression and methylation pattern of RARB, NR4A1 and HSD3B2 genes in human adrenal tissues (HAT) and in pediatric virilizing adrenocortical tumors (VAT) were analyzed. For analysis of the results samples were divided into 3 age groups according to FeZ involution, pre and post-adrenarche ages. In all HAT, similar RARB mRNA was found including microdissected zona reticularis (ZR) and zona fasciculata, but HSD3B2 and NR4A1 mRNAs were lower in ZR (p < 0.05). NR4A1 and RARB promoters remained unmethylated in HAT and VAT. No adrenal zone specific differences in NR4A1 methylation were observed. In summary, RARB was not associated with ZR-specific downregulation of HSD3B2 in postnatal human adrenocotical zonation. DNA methylation would not be involved in NR4A1 adrenocortical cell-type specific downregulation. Lack of CpG islands in HSD3B2 suggested that HSD3B2 ZR-specific downregulation would not be directly mediated by DNA methylation. PMID- 27670691 TI - Streptomyces kronopolitis sp. nov., an actinomycete that produces phoslactomycins isolated from a millipede (Kronopolites svenhedind Verhoeff). AB - A phoslactomycin-producing actinomycete, designated strain NEAU-ML8T, was isolated from a millipede (Kronopolites svenhedind Verhoeff) and characterized using a polyphasic approach. 16S rRNA gene sequence analysis showed that strain NEAU-ML8T belongs to the genus Streptomyces with the highest sequence similarities to Streptomyces lydicus NBRC 13058T (99.39 %) and Streptomyces chattanoogensis DSM 40002T (99.25 %). The maximum-likelihood phylogenetic tree based on 16S rRNA gene sequences showed that the isolate formed a distinct phyletic line with NBRC 13058T and S. chattanoogensis DSM 40002T. This branching pattern was also supported by the tree rconstructed with the neighbour-joining method. A combination of DNA-DNA hybridization experiments and phenotypic tests were carried out between strain NEAU-ML8T and its phylogenetically closely related strains, which further clarified their relatedness and demonstrated that NEAU-ML8T could be distinguished from NBRC 13058T and S. chattanoogensis DSM 40002T. Therefore, it is concluded that strain NEAU-ML8T can be classified as representing a novel species of the genus Streptomyces, for which the name Streptomyces kronopolitis sp. nov. is proposed. The type strain is NEAU-ML8T (=DSM 101986T=CGMCC 4.7323T). PMID- 27670693 TI - PUBLIC AND PATIENT INVOLVEMENT IN HEALTH TECHNOLOGY ASSESSMENT: A FRAMEWORK FOR ACTION. AB - OBJECTIVE: As health technology assessment (HTA) organizations in Canada and around the world seek to involve the public and patients in their activities, frameworks to guide decisions about whom to involve, through which mechanisms, and at what stages of the HTA process have been lacking. The aim of this study was to describe the development and outputs of a comprehensive framework for involving the public and patients in a government agency's HTA process. METHODS: The framework was informed by a synthesis of international practice and published literature, a dialogue with local, national and international stakeholders, and the deliberations of a government agency's public engagement subcommittee in Ontario, Canada. RESULTS: The practice and literature synthesis failed to identify a single, optimal approach to involving the public and patients in HTA. Choice of methods should be considered in the context of each HTA stage, goals for incorporating societal and/or patient perspectives into the process, and relevant societal and/or patient values at stake. The resulting framework is structured around four actionable elements: (i) guiding principles and goals for public and patient involvement (PPI) in HTA, (ii) the establishment of a common language to support PPI efforts, (iii) a flexible array of PPI approaches, and (iv) on-going evaluation of PPI to inform adjustments over time. CONCLUSIONS: A public and patient involvement framework has been developed for implementation in a government agency's HTA process. Core elements of this framework may apply to other organizations responsible for HTA and health system quality improvement. PMID- 27670692 TI - Phylogenesys and homology modeling in Zika virus epidemic: food for thought. AB - Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified. Brazilian strains clustered all together and closely related to the French Polynesia isolates. A strong presence of a negatively selected site in the envelope gene (Env) protein was evidenced, suggesting a probable purging of deleterious polymorphisms in functionally important genes. Our results show relative conservancy of ZIKV sequences when envelope and other non-structural proteins (NS3 and NS5) are analyzed by homology modeling. However, some regions within the consensus sequence of NS5 protein and to a lesser extent in the envelope protein, show localized high mutation frequency corresponding to a considerable alteration in protein stability. In terms of viral immune escape, envelope protein is under a higher selective pressure than NS5 and NS3 proteins for HLA class I and II molecules. Moreover, envelope mutations that are not strictly related to T-cell immune responses are mostly located on the surface of the protein in putative B cell epitopes, suggesting an important contribution of B cells in the immune response as well. PMID- 27670694 TI - Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase. AB - BACKGROUND: Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. OBJECTIVE: In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. METHOD: The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. RESULTS: Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. CONCLUSION: MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme. PMID- 27670695 TI - The role of Dickkopf-1 in joint remodeling and fibrosis: A link connecting spondyloarthropathies and scleroderma? AB - BACKGROUND: Dickkopf-1 (Dkk-1) is a soluble inhibitor of the canonical Wnt pathway, which plays critical roles in embryonic development. Evidence suggests that this molecule regulates several aspects of both bone biology and fibrosis. OBJECTIVES: To provide an overview of our current knowledge of the role of Dkk-1 in joint remodeling and fibrosis. METHODS: We performed an electronic search (Medline) using the following key words: Dickkopf-1 (or Dkk-1), new bone formation, joint remodeling, ankylosing spondylitis, systemic sclerosis (or scleroderma), and fibrosis, supplemented by a manual search of references from retrieved articles. RESULTS: Dkk-1 is a master regulator of joint remodeling in animal models of arthritis shifting the balance toward new bone formation when its expression is decreased and toward erosion/joint destruction when its expression is increased. In humans, evidence suggests that Dkk-1 may be dysfunctional in patients with ankylosing spondylitis, a prototype bone forming disease. Moreover, data from animal models indicate that Dkk-1 has a protective role against fibrosis in several organs. Recent data suggest that inhibiting the canonical Wnt pathway by overexpression of Dkk-1 could be a way to target TGF beta signaling in fibrotic diseases. Finally, B-cell depletion therapy in systemic sclerosis may exert its effects through TGF-beta dependent upregulation of Dkk-1. CONCLUSIONS: Dkk-1 appears to play a crucial role in both joint remodeling/ectopic ossification and fibrosis, and may be a prospective therapeutic modality for fibrotic diseases or diseases characterized by pathologic joint remodeling. PMID- 27670696 TI - Design and Usability Evaluation of Social Mobile Diabetes Management System in the Gulf Region. AB - BACKGROUND: The prevalence of diabetes in the Gulf States is one of the highest globally. It is estimated that 20% of the population in the region has been diagnosed with diabetes and according to the International Diabetes Federation (IDF), five of the IDF's "top 10" countries for diabetes prevalence in 2011 and projected for 2030 are in this region. In recent years, there have been an increasing number of clinical studies advocating the use of mobile phone technology for diabetes self-management with improved clinical outcomes. However, there are few studies to date addressing the application of mobile diabetes management in the Gulf region, particularly in the Kingdom of Saudi Arabia (KSA), where there is exponential increase in mobile phone usage and access to social networking. OBJECTIVE: The objective of this paper is to present the design and development of a new mobile health system for social behavioral change and management tailored for Saudi patients with diabetes called Saudi Arabia Networking for Aiding Diabetes (SANAD). A usability study for the SANAD system is presented to validate the acceptability of using mobile technologies among patients with diabetes in the KSA and the Gulf region. METHODS: The SANAD system was developed using mobile phone technology with diabetes management and social networking modules. For the usability study the Questionnaire for User Interaction Satisfaction was used to evaluate the usability aspect of the SANAD system. A total of 33 users with type 2 diabetes participated in the study. RESULTS: The key modules of the SANAD system consist of (1) a mobile diabetes management module; (2) a social networking module; and (3) a cognitive behavioral therapy module for behavioral change issues. The preliminary results of the usability study indicated general acceptance of the patients in using the system with higher usability rating in patients with type 2 diabetes. CONCLUSIONS: We found that the acceptability of the system was high among Saudi patients with diabetes, and ongoing work in this research area is underway to conduct a clinical pilot study in the KSA for patients with type 2 diabetes. The wide deployment of such a system is timely and required in the Gulf region due to the wide use of mobile phones and social networking mediums. PMID- 27670697 TI - The genome-wide mutational landscape of pituitary adenomas. PMID- 27670700 TI - Pyoadenomyosis: A Rare Complication of Adenomyosis. PMID- 27670701 TI - Pyoadenomyose: rare complication de l'adenomyose. PMID- 27670698 TI - Elongator controls cortical interneuron migration by regulating actomyosin dynamics. AB - The migration of cortical interneurons is a fundamental process for the establishment of cortical connectivity and its impairment underlies several neurological disorders. During development, these neurons are born in the ganglionic eminences and they migrate tangentially to populate the cortical layers. This process relies on various morphological changes that are driven by dynamic cytoskeleton remodelings. By coupling time lapse imaging with molecular analyses, we show that the Elongator complex controls cortical interneuron migration in mouse embryos by regulating nucleokinesis and branching dynamics. At the molecular level, Elongator fine-tunes actomyosin forces by regulating the distribution and turnover of actin microfilaments during cell migration. Thus, we demonstrate that Elongator cell-autonomously promotes cortical interneuron migration by controlling actin cytoskeletal dynamics. PMID- 27670703 TI - Attendez une minute et faites un chois reflechi. PMID- 27670702 TI - Don't Just Do Something, Stand There. PMID- 27670699 TI - Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma. AB - Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer. Our current knowledge of oncogenic drivers in this specific subtype of lung cancer is largely limited compared with lung adenocarcinoma (ADC). Through exon array analyses, molecular analyses and functional studies, we here identify the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC. We found that this gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Through mechanistic studies, we further revealed that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2 MMP1 signaling axis. We show that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression. These findings improve our current knowledge of oncogenic drivers in lung SCC and provide a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion. PMID- 27670704 TI - Adhesion Assessment at First Repeat Caesarean Section With or Without Prior Adhesion Barrier Use. AB - OBJECTIVE: To determine if placing a carboxymethylcellulose adhesion barrier material at the time of primary Caesarean section (CS) leads to a reduction in adhesive disease, clinical outcomes, and hospital costs encountered at the time of a first repeat CS. METHODS: We performed a prospective cohort study of women at a large community hospital undergoing a first repeat CS with available prior operative records. A rating scale assessing the location and severity of adhesions (range 0 = no adhesions to 3 = dense and/or vascular adhesions requiring electrocautery) at the time of repeat CS was utilized by obstetric residents blinded to previous adhesion barrier use. RESULTS: One hundred fourteen women met the criteria for the study and were enrolled; 34 women had been exposed to the carboxymethylcellulose adhesion barrier and 80 had not. Demographics and clinical factors were similar between groups. In women exposed and not exposed to the barrier, there were differences in mean ratings of adhesions between fascia and muscle (1.18 +/- 1.00 vs. 1.67 +/- 0.83, P = 0.012, Cohen's d = 0.53) and the overall adhesion rate (67.6% vs. 91.3%; P = 0.004); there were also differences in mean ratings of adhesions between the uterus and omentum (0.00 +/- 0.00 vs. 0.19 +/- 0.53, P = 0.032, Cohen's d = 0.51) and the overall adhesion rate (0% vs. 12.5%; P = 0.032). No differences between the groups in time from incision to delivery, operating time, blood loss, or hospital costs were noted at first repeat CS. CONCLUSION: Use of a carboxymethylcellulose adhesion barrier is associated with a decrease in adhesions noted at the time of repeat CS. The limited clinical benefits observed do not support use of the material for prevention of adhesions after the first CS. PMID- 27670705 TI - Type of Labour in the First Pregnancy and Cumulative Perinatal Morbidity. AB - OBJECTIVE: To estimate cumulative perinatal morbidity among infants delivered at term, according to the type of labour in the first pregnancy, when the first pregnancy was low risk. METHODS: In a 26-year population-based cohort study (1988 2013) using the Nova Scotia Atlee Perinatal Database, we identified the type of labour in successive pregnancies in low-risk, nulliparous women at term in their first pregnancy (who had at least one subsequent pregnancy), and also identified perinatal outcomes in subsequent deliveries according to the type of labour in the first pregnancy. RESULTS: A total of 37 756 pregnancies satisfied inclusion and exclusion criteria; of these, 1382 (3.7%) had a Caesarean section without labour in the first pregnancy. Rates of most adverse perinatal outcomes were low (<= 1%). The risks for stillbirth were low in subsequent deliveries, including those that followed CS without labour in the first pregnancy, and the risks for the overall severe perinatal morbidity outcome were less than 10% for all subsequent deliveries. CONCLUSION: The absolute risks for severe perinatal morbidity outcomes in a population of low-risk women (with up to four additional pregnancies) were small, regardless of type of labour in the first pregnancy. This finding provides important information on perinatal outcomes in subsequent pregnancies when considering type of labour in the first pregnancy. PMID- 27670706 TI - Clinicians' Perspectives and Experiences Regarding Maternity Care in Women With Vulvodynia. AB - OBJECTIVE: To assess clinicians' frequency of and comfort with provision of maternity care for women with vulvodynia, their beliefs and practices regarding delivery mode, and frequency of maternal requests for Caesarean section (CS). METHODS: We invited physicians and midwives to complete a questionnaire assessing their frequency of contact with pregnant women with vulvodynia; their level of comfort providing antenatal, intrapartum, and postpartum care for these women; whether they believed that vulvodynia is an indication for elective CS and the frequency of making this recommendation; and the number of patients with vulvodynia who strongly requested CS. RESULTS: Of the 140 participating clinicians, 91 were physicians and 49 were midwives. Most physicians (n = 64; 70.4%) saw patients with vulvodynia at least once per month. Clinicians who saw women with vulvodynia were most likely to see pregnant women with vulvodynia rarely (n = 54; 40.3%) or every six to 12 months (n = 29; 21.6%). Almost one third (n = 44; 31.4%) were not comfortable providing maternity care for these women, and 16.4% (n = 23) agreed that vulvodynia was an indication for elective CS. Of respondents who provided maternity care for women with vulvodynia, 15.4% (n = 18) had recommended CS; the most common reason for doing so was potential worsening of vulvar symptoms. The majority of clinicians who provided maternity care for women with vulvodynia (n = 73; 62.4%) indicated that maternal requests for CS were rare. CONCLUSION: Almost one third of participating clinicians (31.4%) were not comfortable providing maternity care for women with vulvodynia. Despite infrequent maternal requests, a minority of clinicians believed that vulvodynia is an indication for CS and/or made that recommendation. Additional research and education are needed to provide optimal obstetric care for women with vulvodynia. PMID- 27670707 TI - The Unmet Contraceptive Need of Incarcerated Women in Ontario. AB - OBJECTIVE: Studies from the United States have shown that women in correctional facilities have higher rates of unintended pregnancy and unmet need for contraception compared with the general population, and that the provision of family planning services in correctional facilities may improve access to contraception. No study has examined these issues in women in correctional facilities in Canada. We aimed to describe the rates of unintended pregnancy and contraceptive use for incarcerated women in Ontario. METHODS: Women in a provincial correctional facility in Ontario completed a written survey in 2014. We calculated the prevalence of prior unintended pregnancy, prior therapeutic abortion, and contraception use. We calculated the unmet need for contraception, defined as the proportion of women who were not using reliable contraception among women who were sexually active and were not trying to conceive. RESULTS: Of 85 participants, 82% had been pregnant, and of these women, 77% had experienced an unintended pregnancy and 57% reported having undergone a therapeutic abortion. Regarding the most recent pregnancy, 72% of women scored their pregnancy intention as unplanned or ambivalent. Of women who were at risk for unintended pregnancy prior to incarceration, 80% were not using a reliable form of contraception. CONCLUSION: Incarcerated women in Ontario have higher rates of unintended pregnancy and unmet need for contraception than does the general population. The provision of family planning services during and after incarceration may improve the health of individuals and reduce costs for society overall. PMID- 27670708 TI - The Long-Term Pelvic Floor Health Outcomes of Women After Childbirth: The Influence of Labour in the First Pregnancy. AB - OBJECTIVE: To estimate the influence of labour and pregnancy factors on long-term pelvic floor health outcomes. METHODS: This population-based cohort study was conducted using linkage between the Nova Scotia Atlee Perinatal Database, the Medical Services Insurance Database, and the Canadian Institute for Health Information's Discharge Abstract Database from 1988 to 2006; this allowed for the evaluation of patient utilization of care providers for pelvic floor disorders and captured conservative and surgical interventions. We compared rates of urinary and anal incontinence, pelvic organ prolapse, and fistula disorders in women undergoing Caesarean section (CS) without labour and women undergoing labour with any method of delivery. Multivariate logistic regression and survival (time-to-event) analyses were performed. RESULTS: Absolute risks for the selected pelvic floor health outcomes were low, regardless of whether labour was experienced in the first pregnancy. Women with one or more deliveries who had a CS without labour in their first pregnancy had reduced risks for all pelvic floor health outcomes, except fistula formation, and they were also less likely to develop these outcomes during the study period. CONCLUSION: Women undergoing obstetrically indicated CS without labour in their first delivery may have reduced risks of pelvic floor health disorders, even after multiple deliveries. These findings contribute important information for health care providers when counselling women and their families who are weighing the risk of long-term pelvic floor disorders against the benefits of spontaneous vaginal delivery. PMID- 27670709 TI - Complete Mesh Infection Following Repeat Retropubic Tension-Free Vaginal Tape. AB - BACKGROUND: Midurethral slings are the most widely used surgical treatment for stress urinary incontinence. Complications include bladder injury, voiding dysfunction, mesh exposure/erosion, dyspareunia, and failure to correct the incontinence. Complete mesh infection is rare. CASE: A 48-year-old woman underwent a repeat retropubic tension-free vaginal tape (TVT) procedure for stress urinary incontinence. She presented eight weeks postoperatively with a tender suprapubic mass and urinary retention. A CT scan demonstrated thickening of the bladder wall and cystoscopy revealed severe inflammation with no intramural injury. The sling appeared to be infected and was removed vaginally. The patient's symptoms resolved following removal of the sling. CONCLUSION: Mesh infection following a midurethral sling procedure is rare. In suspected cases, cystoscopy should be performed to rule out bladder injury. Antibiotic therapy may be successful, but removal of the sling may be required for resolution of symptoms. PMID- 27670710 TI - Management of Spontaneous Labour at Term in Healthy Women. AB - OBJECTIVE: The purpose of this guideline is to provide guidance for the intrapartum management of spontaneous labour, whether normal or abnormal, in term, healthy women, and to provide guidance in the management of first and second stage dystocia to increase the likelihood of a vaginal birth and optimize birth outcomes. EVIDENCE: Published literature was retrieved through searches of PubMed and the Cochrane Library in October 2011 using appropriate, controlled vocabulary (e.g., labour pain; labour, obstetric; dystocia) and key words (e.g., obstetric labor, perineal care, dysfunctional labor). When appropriate, results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Results were limited to the last 10 years. Searches were updated on a regular basis and incorporated in the guideline up to June 15, 2015. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). SUMMARY STATEMENTS: RECOMMENDATIONS. PMID- 27670711 TI - Prise en charge du travail spontane chez les femmes en sante, a terme. AB - OBJECTIF: La presente directive vise a fournir des conseils concernant la prise en charge du travail spontane intrapartum, normal ou anormal, a terme, chez les femmes en sante, ainsi que des conseils relatifs a la prise en charge de la dystocie lors du premier et du deuxieme stade du travail, pour favoriser l'accouchement vaginal et optimiser les issues de la grossesse. DONNeES PROBANTES: Des documents publies ont ete recuperes au moyen de recherches effectuees dans PubMed et la Cochrane Library, en octobre 2011, a partir d'une terminologie appropriee et controlee (p. ex., labour pain; labour, obstetric; dystocia) et de mots-cles (p. ex., obstetric labor, perineal care, dysfunctional labor). Lorsque cela convenait, on n'a tenu compte que des resultats qui proviennent de revues systematiques, d'essais controles aleatoires ou d'essais cliniques controles et d'etudes d'observation. Seuls les resultats des 10 dernieres annees ont ete pris en consideration; les recherches ont ete regulierement mises a jour jusqu'au 15 juin 2015 et integrees a la directive. VALEURS: La qualite des donnees probantes a ete evaluee en fonction des criteres decrits dans le Rapport du Groupe d'etude canadien sur les soins de sante preventifs (tableau 1). DeCLARATIONS SOMMAIRES: RECOMMANDATIONS. PMID- 27670712 TI - Catalytic Anti-Markovnikov Transformations of Hindered Terminal Alkenes Enabled by Aldehyde-Selective Wacker-Type Oxidation. AB - A new strategy for the functionalization of sterically hindered terminal olefins is reported. Alkenes bearing quaternary carbons at the allylic or homoallylic position are readily oxidized to the corresponding aldehydes by palladium/copper/nitrite catalysis. A broad range of functional groups including esters, nitriles, silyl ethers, vinylogous esters, ketones, lactones, and beta ketoesters are tolerated under the reaction conditions. The crude aldehyde products can be transformed further, enabling direct conversion of hindered terminal alkenes to various other synthetically useful functional groups, resulting in formal anti-Markovnikov hydroamination, among other transformations. PMID- 27670713 TI - Observable indicators and behaviors for the identification of problem gamblers in venue environments. AB - Background and aims In many jurisdictions, where gambling services are provided, regulatory codes require gambling operators to apply a duty of care toward patrons. A common feature of these provisions is some expectation that venue staff identify and assist patrons who might be experiencing problems with their gambling. The effectiveness of such measures is, however, predicated on the assumption that there are reliable and observable indicators that might be used to allow problem gamblers to be distinguished from other gamblers. Methods In this study, we consolidate the findings from two large Australian studies (n = 505 and n = 680) of regular gamblers that were designed to identify reliable and useful indicators for identifying problem gambling in venues. Results It was found that problem gamblers are much more likely to report potentially visible emotional reactions, unusual social behaviors, and very intense or frenetic gambling behavior. Discussion and conclusions This study shows that there are a range of indicators that could potentially be used to identify people experiencing problems in venues, but that decisions are most likely to be accurate if based on an accumulation of a diverse range of indicators. PMID- 27670714 TI - New Insights into the Phage Genetic Switch: Effects of Bacteriophage Lambda Operator Mutations on DNA Looping and Regulation of PR, PL, and PRM. AB - One of the best understood systems in genetic regulatory biology is the so-called "genetic switch" that determines the choice the phage-encoded CI repressor binds cooperatively to tripartite operators, OL and OR, in a defined pattern, thus blocking the transcription at two lytic promoters, PL and PR, and auto-regulating the promoter, PRM, which directs CI synthesis by the prophage. Fine-tuning of the maintenance of lysogeny is facilitated by interactions between CI dimers bound to OR and OL through the formation of a loop by the intervening DNA segment. By using a purified in vitro transcription system, we have genetically dissected the roles of individual operator sites in the formation of the DNA loop and thus have gained several new and unexpected insights into the system. First, although both OR and OL are tripartite, the presence of only a single active CI binding site in one of the two operators is sufficient for DNA loop formation. Second, in PL, unlike in PR, the promoter distal operator site, OL3, is sufficient to directly repress PL. Third, DNA looping mediated by the formation of CI octamers arising through the interaction of pairs of dimers bound to adjacent operator sites in OR and OL does not require OR and OL to be aligned "in register", that is, CI bound to "out-of-register" sub-operators, for example, OL1~Ol2 and OR2~OR3, can also mediate loop formation. Finally, based on an examination of the mechanism of activation of PRM when only OR1 or OR2 are wild type, we hypothesize that RNA polymerase bound at PR interferes with DNA loop formation. Thus, the formation of DNA loops involves potential interactions between proteins bound at numerous cis acting sites, which therefore very subtly contribute to the regulation of the "switch". PMID- 27670717 TI - A meta-analysis of cardiovascular events in intermittent androgen-deprivation therapy versus continuous androgen-deprivation therapy for prostate cancer patients. PMID- 27670716 TI - Growing Slowly 1 locus encodes a PLS-type PPR protein required for RNA editing and plant development in Arabidopsis. AB - Most pentatricopeptide repeat (PPR) proteins are involved in organelle post transcriptional processes, including RNA editing. The PPR proteins include the PLS subfamily, containing characteristic triplets of P, L, and S motifs; however, their editing mechanisms and roles in developmental processes are not fully understood. In this study, we isolated the Arabidopsis thaliana Growing slowly 1 (AtGRS1) gene and showed that it functions in RNA editing and plant development. Arabidopsis null mutants of grs1 exhibit slow growth and sterility. Further analysis showed that cell division activity was reduced dramatically in the roots of grs1 plants. We determined that GRS1 is a nuclear-encoded mitochondria localized PPR protein, and is a member of the PLS subfamily. GRS1 is responsible for the RNA editing at four specific sites of four mitochondrial mRNAs: nad1-265, nad4L-55, nad6-103, and rps4-377 The first three of these mRNAs encode for the subunits of complex I of the electron transport chain in mitochondria. Thus, the activity of complex I is strongly reduced in grs1 Changes in RPS4 editing in grs1 plants affect mitochondrial ribosome biogenesis. Expression of the alternative respiratory pathway and the abscisic acid response gene ABI5 were up-regulated in grs1 mutant plants Genetic analysis revealed that ABI5 is involved in the short root phenotype of grs1 Taken together, our results indicate that AtGRS1 regulates plant development by controlling RNA editing in Arabidopsis. PMID- 27670715 TI - An Adaptive Mutation in Enterococcus faecium LiaR Associated with Antimicrobial Peptide Resistance Mimics Phosphorylation and Stabilizes LiaR in an Activated State. AB - The cyclic antimicrobial lipopeptide daptomycin (DAP) triggers the LiaFSR membrane stress response pathway in enterococci and many other Gram-positive organisms. LiaR is the response regulator that, upon phosphorylation, binds in a sequence-specific manner to DNA to regulate transcription in response to membrane stress. In clinical settings, non-susceptibility to DAP by Enterococcus faecium is correlated frequently with a mutation in LiaR of Trp73 to Cys (LiaRW73C). We have determined the structure of the activated E. faecium LiaR protein at 3.2A resolution and, in combination with solution studies, show that the activation of LiaR induces the formation of a LiaR dimer that increases LiaR affinity at least 40-fold for the extended regulatory regions upstream of the liaFSR and liaXYZ operons. In vitro, LiaRW73C induces phosphorylation-independent dimerization of LiaR and provides a biochemical basis for non-susceptibility to DAP by the upregulation of the LiaFSR regulon. A comparison of the E. faecalis LiaR, E. faecium LiaR, and the LiaR homolog from Staphylococcus aureus (VraR) and the mutations associated with DAP resistance suggests that physicochemical properties such as oligomerization state and DNA specificity, although tuned to the biology of each organism, share some features that could be targeted for new antimicrobials. PMID- 27670718 TI - Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer. AB - BACKGROUND: Despite palliative benefits and PSA responses, the objective clinical impact of daily oral prednisone (P) for metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent P to evaluate its impact on overall survival (OS) and toxicities. METHODS: Individual patient data from control arms of randomized trials of men with mCRPC who received placebo or P+placebo post docetaxel were eligible for analysis. The impact of P on OS and severe toxicities was investigated in Cox regression models adjusted for known prognostic factors. Statistical significance was defined as P<0.05 and all tests were two sided. RESULTS: Data from the control arms of two randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n=394) administered P plus placebo and the CA184-043 trial (n=400) administered placebo alone. P plus placebo was not significantly associated with OS compared with placebo in a multivariable analysis (hazard ratio=0.89 (95% confidence interval 0.72-1.10), P=0.27). Other factors associated with poor OS were Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ?1, Gleason score ?8, liver metastasis, high PSA, hypoalbuminemia and elevated lactate dehydrogenase (LDH). Grade ?3 therapy-related toxicities were significantly increased with P plus placebo compared with placebo (hazard ratio=1.48 (95% confidence interval 1.03-2.13), P=0.034). Other baseline factors significantly associated with a higher risk of grade ?3 toxicities were ECOG-PS ?1, hypoalbuminemia and elevated LDH. Fatigue, asthenia, anorexia and pain were not different based on P administration. CONCLUSIONS: P plus placebo was associated with higher grade ?3 toxicities but not extension of OS compared with placebo alone in men with mCRPC who received prior docetaxel. Except for the use of P with abiraterone to alleviate toxicities, the use of P should be questioned given its association with toxicities and resistance. PMID- 27670719 TI - Expanding functions of ADP-ribosylation in the maintenance of genome integrity. AB - Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD+ as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair. Still, efforts made on understanding the role of PARylation in DNA repair continues to yield novel discoveries. Over the last years, our knowledge in this field has been particularly advanced by the discovery of novel biochemical and functional properties featuring PARP1, by the characterization of the other PARP family members and by the identification of a panel of enzymes capable of erasing poly(ADP-ribose). The aim of this review is to provide an overview of these newest findings and their relevance in genome surveillance. PMID- 27670720 TI - Beyond mice: Emerging and transdisciplinary models for the study of early-onset myopathies. AB - The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early onset myopathies. However strategies based on simple animal models and on transdisciplinary approaches exploring mechanical muscle cell properties emerge as attractive, non-exclusive alternatives. These new ways provide valuable opportunities to improve our knowledge on how mechanical, biochemical, and genetic/epigenetic cues modulate the formation, organization and function of muscle tissues. Here we provide an overview of how single cell and micro-tissue engineering in parallel to non-mammalian, Drosophila and zebrafish models could contribute to filling gaps in our understanding of pathogenic mechanisms underlying early-onset myopathies. We also discuss their potential impact on designing new diagnostic and therapeutic strategies. PMID- 27670721 TI - Fibrosis development in early-onset muscular dystrophies: Mechanisms and translational implications. AB - Duchenne muscular dystrophy (DMD) is one of the most devastating neuromuscular genetic diseases caused by the absence of dystrophin. The continuous episodes of muscle degeneration and regeneration in dystrophic muscle are accompanied by chronic inflammation and fibrosis deposition, which exacerbate disease progression. Thus, in addition of investigating strategies to cure the primary defect by gene/cell therapeutic strategies, increasing efforts are being placed on identifying the causes of the substitution of muscle by non-functional fibrotic tissue in DMD, aiming to attenuate its severity. Congenital muscular dystrophies (CMDs) are early-onset diseases in which muscle fibrosis is also present. Here we review the emerging findings on the mechanisms that underlie fibrogenesis in muscular dystrophies, and potential anti-fibrotic treatments. PMID- 27670722 TI - Unbalanced lateral mandibular deviation associated with TMJ sound as a sign in TMJ disc dysfunction diagnosis. AB - The aim was to study the characteristics of lateral mandibular horizontal deviations during opening-closing movements and their association with TMJ sounds of the clicking type. Subjects were 28 healthy volunteers and 38 patients diagnosed with MRI imaging as having TMJ disc dysfunction, 22 with disc displacement without (DD) and 16 as having disc displacement with reduction (DDR). TMJ sounds were recorded with miniature microphones placed in the ear canals, and jaw movements were documented with a kinesiograph. A sign, unbalanced lateral deviation (ubd) was defined as a rapid, short duration, change in jaw movement direction from, and back to, a smooth deviation path in the horizontal plane. The hypotheses were that degrees of maximal deviations, proportions of unbalanced deviation (ubd) and such deviation associated with TMJ sounds (ubdS), differ between healthy subjects and patients with DD or DDR. Comparisons between groups were made using one-way anova and chi-square analysis, as appropriate. No differences were found between groups regarding degree of lateral deviation per se. The proportions of ubd and ubdS were significantly higher in patients with DDR than in healthy subjects and than in patients with DD (P < 0.001), but no such differences were found between healthy subjects and patients with DD. For prediction of DDR, the sensitivity and specificity of the sign ubdS were found to be 68.8% and 89.3%, respectively. For the sign ubd, they were 100.0% and 64.3%. This indicates that the sign ubdS has diagnostic value in screening for DDR. PMID- 27670723 TI - [Purple drank: A dangerous cocktail]. AB - "Purple drank" is a dangerous hallucinogenic cocktail commonly used by teenagers, made popular by American rappers and social networks. It combines codeine-based cough syrup, antihistamines such as promethazine, and soda. Unknown by caregivers, it may be responsible for serious neuropsychological complications. We report the effects of this new risky behavior in three patients: a 14-year-old girl and her boyfriend, both found in an initial state of drowsiness, followed by hallucinations and anticholinergic toxidrome; and another teenager whose chronic use led to addiction with increasing doses. It is important to identify signs of such intoxication and to inform patients about the risks of respiratory depression, drowsiness, and delirium linked to acute medication misuse. PMID- 27670724 TI - [Diffuse cutaneous mastocytosis of an infant: A case report]. AB - Mastocytosis is a group of diseases related to abnormal accumulation and proliferation of mast cells in one or more organs. They may be associated with an acquired point mutation and the activation of the receptor tyrosine-kinase c-KIT of CFS (mast cell growth factor). The clinical manifestations are varied and secondary to the release of mast cell mediators and/or infiltration of various organs. There are two main types of mastocytosis: pure cutaneous mastocytosis and systemic mastocytosis when more than two organs are involved in mast cell infiltration (bone marrow, gastrointestinal tract, bone, liver and spleen, lymph nodes). Mastocytosis affects children in two thirds of cases, most frequently as an isolated cutaneous form. The most common clinical form in children is urticaria pigmentosa and solitary mastocytoma; bullous diffuse mastocytosis is rare. We report the case of an 8-month-old infant who presented with a diffuse pruritic bullous eruption. The histology and immunohistochemistry results were suggestive of mastocytosis. A serum tryptase test yielded positive results. Laboratory investigations did not identify systemic involvement. The patient was given antihistamine H1 medication and local care. Advice regarding the disease was offered to the parents. The course of the disease was marked by a decrease in the number of blisters and attenuation of the pruritus at the 6-month follow-up. This observation emphasizes the importance of awareness of this rare entity, which should be considered in all cases of bullous dermatosis in children, thereby allowing for early treatment. PMID- 27670725 TI - Characterization of protein quality control components via dual reporter containing misfolded cytosolic model substrates. AB - Protein misfolding and protein aggregation are causes of severe diseases as neurodegenerative disorders, diabetes and cancer. Therefore, the cell has to constantly monitor the folding status of its proteome. Chaperones and components of the ubiquitin-proteasome system are key players in the cellular protein quality control process. In order to characterize components of the protein quality control system in a well-established model eukaryote - the yeast Saccharomyces cerevisiae - we established new cytosolic model substrates based on firefly luciferase and beta-isopropylmalate dehydrogenase (Leu2). The use of these two different enzymes arranged in tandem as reporters enabled us to analyse the folding status and the degradation propensity of these new model substrates in yeast cells mutated in components of the cellular protein quality control system. The Hsp70 chaperone system known to be essential in the cellular protein quality control was chosen as a model for showing the high value of the luciferase-based model substrates in the characterization of components of the cytosolic protein quality control system in yeast. PMID- 27670726 TI - Structural analysis of macromolecular levan produced by Bacillus megaterium GJT321 based on enzymatic method. AB - Extracellular polysaccharide (EPS) produced by Bacillus megaterium GJT321 was isolated from fermentation broth and further purified by gel filtration chromatography. The molecular weight of EPS was estimated as 1946kDa by gel permeation chromatography (GPC), so this EPS was determined as macromolecular polysaccharide. Fourier transform infrared spectrometry (FT-IR) showed that the kind of heterocyclic compound composing EPS was furanose. The structural characteristics of EPS were investigated by means of enzymatic method, electrospray ionization mass spectrometry (ESI-MS) and NMR spectra analysis. The structure elucidation of the EPS was accomplished, and it was beta - (2, 6) -D- fructofuranose, namely levan. PMID- 27670727 TI - Effect of pullulan on gel properties of Scomberomorus niphonius surimi. AB - Pullulan possesses uniquely good structural flexibility and solubility. Surimi is an aquatic product prepared from minced fish flesh, which is washed to remove most lipids, blood, enzymes and sarcoplasmic proteins. However, data on effect of pullulan on gel properties of fish surimi are limited. This study investigated the influence of pullulan at different concentrations (0-2g/100 g wet materials) on the properties of Scomberomorus niphonius surimi gel including the water holding capacity, adhesiveness, cohesiveness and microstructure. The addition of pullulan increased the water holding capacity, adhesiveness and cohesiveness and formed a more stable and ordered three-dimensional gel complex. Therefore, the addition of pullulan increased the gel properties of S. niphonius surimi gel. PMID- 27670728 TI - Homogeneous carboxymethylated orange pulp cellulose: Characterization and evaluation in terms of drug delivery. AB - The aim of the present study is to develop an environment-friendly method to convert orange pulp wastes to Carboxymethyl cellulose (CMC) by homogeneous substitution. Carboxymethylation of Orange pulp treated with alkaline PEG solutions was investigated and characterized by means of TGA, DSC, XRD and SEM and compared with commercial CMC. The TGA data reveals that shifting of peaks was observed towards lower temperature with increase in monochloroacetic acid (MCA). SEM studies showed greater blending of particulate powder with increasing MCA content. The crystallinity of synthesized CMC was found to be lower than the commercial CMC. Finally, the cellulosic materials were evaluated for the formulation and dissolution studies of prepared tablets. Dissolution release studies shows that synthesized cellulose (CMCOP5, CMCOP8, CMCOP11) release up to 70.1+/-0.04%, whereas the commercial CMC 78.184+/-0.07% in 8h respectively and thereby suggests that it may be used in delayed drug delivery and targeting drugs to the colon. The synthesized CMC from orange pulp may be used as substitute for the commercial CMC. PMID- 27670729 TI - Traumatic injury risk and agricultural transitions: A view from the American Southeast and beyond. AB - OBJECTIVES: Bioarchaeological research has documented a general decline in health with the transition from foraging to farming, primarily with respect to changing patterns of morbidity. Less is known about changes in injury risk, an aspect of health more obviously tied to particular landscapes and behaviors associated with different subsistence regimes. The purpose of this research is to evaluate several hypotheses emerging from the ideal free distribution model (Fretwell & Lucas, ) that predict injury risk based on subsistence-specific practices and land use patterns. MATERIALS AND METHODS: Postcranial fracture frequencies for long bones and clavicles in human skeletal remains from three Southeast U.S. regions permit examination of variability in injury risk among low-intensity (floodplain) farmers. Published data on six hunter-gatherer samples, four low intensity agriculturalist samples, and six high-intensity agriculturalist samples comprise a comparative sample for examining variability in injury risk across three distinct subsistence traditions. Differences are evaluated using Z scores and the Fisher Exact test, Chi-Square test, and Mann-Whitney U test. RESULTS: While statistically significant differences are apparent among low-intensity farming groups in the Southeast sample, in the global comparison postcranial fractures are significantly less common in low-intensity agriculturalists than in hunter-gatherers or high-intensity agriculturalists. DISCUSSION: The results of this study support the hypothesis that, with respect to traumatic injury risk, low-intensity farming is a risk-averse subsistence strategy in comparison with full-time foraging or high-intensity agriculture. These data suggest that it is not agriculture per se that predicts an increase in this health risk, but rather the mode and intensity of agricultural production, findings that have important ramifications for our understanding of the health consequences of major subsistence transitions. PMID- 27670730 TI - Adjustable hydrazine modulation of single-wall carbon nanotube network field effect transistors from p-type to n-type. AB - Single-wall carbon nanotube (SWCNT) network field effect transistors (FETs), which show decent p-type electronic properties, have been fabricated. The use of hydrazine as an aqueous solution and a strong n-type dopant for the SWCNTs is demonstrated in this paper. The electrical properties are obviously tuned by hydrazine treatment at different concentrations on the surface of the SWCNT network FETs. The transport behavior of SWCNTs can be modulated from p-type to n type, demonstrating the controllable and adjustable doping effect of hydrazine. With a higher concentration of hydrazine, more electrons can be transferred from the hydrazine molecules to the SWCNT network films, thus resulting in a change of threshold voltage, carrier mobility and on-current. By cleaning the device, the hydrazine doping effects vanish, which indicates that the doping effects of hydrazine are reversible. Through x-ray photoelectron spectroscopy (XPS) characterization, the doping effects of hydrazine have also been studied. PMID- 27670731 TI - Not all unprofessional behaviors are equal: The creation of a checklist of bad behaviors. AB - INTRODUCTION: Professionalism is a key component of medical education and training. However, there are few tools to aid educators in diagnosing unprofessional behavior at an early stage. The purpose of this study was to employ policy capturing methodology to develop two empirically validated checklists for identifying professionalism issues in early-career physicians. METHOD: In a series of workshops, a professionalism competency model containing 74 positive and 70 negative professionalism behaviors was developed and validated. Subsequently, 23 subject matter experts indicated their level of concern if each negative behavior occurred 1, 2, 3, 4, or 5 or more times during a six-month period. These ratings were used to create a "brief" and "extended" professionalism checklist for monitoring physician misconduct. RESULTS: This study confirmed the subjective impression that some unprofessional behaviors are more egregious than others. Fourteen negative behaviors (e.g. displaying obvious signs of substance abuse) were judged to be concerning if they occurred only once, whereas many others (e.g. arriving late for conferences) were judged to be concerning only when they occurred repeatedly. DISCUSSION: Medical educators can use the professionalism checklists developed in this study to aid in the early identification and subsequent remediation of unprofessional behavior in medical students and residents. PMID- 27670732 TI - Near-infrared Fluorescence-guided Sentinel Node Mapping of the Ovary With Indocyanine Green in a Minimally Invasive Setting: A Feasible Study. AB - Sentinel lymph node (SLN) mapping has increased its feasibility in both early stage cervical and endometrial cancer. There are few SLN studies regarding the ovary because of the risk of tumor dissemination and perhaps because the ovary represents an inconvenient site for injection. In this preliminary study, we have shown the feasibility of SLN mapping of the ovary with indocyanine green during laparoscopic retroperitoneal aortic surgical staging. The 10 women who were included in this study underwent aortic with pelvic laparoscopic staging, which included SLN biopsy, extrafascial total hysterectomy, and bilateral salpingo oophorectomy in case of an ovarian tumor. The fluorescent dye was injected on the dorsal and ventral side of the proper ovarian ligament and the suspensory ligament, close to the ovary and just underneath the peritoneum. In all cases except 1, SLNs were detected soon after the injection in the aortic compartment and in 3 cases also in the common iliac region. Only 1 intraoperative complication occurred: a superficial lesion of the vena cava that was recovered with a laparoscopic suture. Laparoscopic ovarian SLN mapping performed by means of an injection of indocyanine green fluorescent tracer in the ovarian ligaments seems feasible and promising. Further investigation are encouraged and necessary to evaluate the possible applications of this new technique for staging patients with early-stage ovarian cancer. PMID- 27670733 TI - [New recommendations of 2016 European Guidelines for the diagnosis and treatment of heart failure]. PMID- 27670734 TI - [Cutaneous larva migrans. A case report]. PMID- 27670735 TI - [Painful erythematous macular lesion in the ankle of a young woman]. PMID- 27670736 TI - The prevalence of autoantibody and its relationship with genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection. AB - The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti-HCV positive and 86 anti HCV negative patients were included in the study. Anti-HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse-line blot hybridization. Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), Anti mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti-HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies. PMID- 27670737 TI - Probabilistic analysis of the specific absorption rate intersubject variability safety factor in parallel transmission MRI. AB - PURPOSE: Specific absorption rate (SAR) calculations in parallel transmission are commonly performed by using electromagnetic simulations on generic models. In this study, we propose a probabilistic analysis to study the safety factor employed to account for SAR intersubject variability versus risk relationship in head imaging at 7T. METHODS: Thirty-three finite-element electromagnetic simulations were conducted to sample the four-dimensional parameter space consisting of the head length, head breadth, and shifts in Z and Y random variables. Based on the SAR matrices for each configuration, a multivariate second-order polynomial of the SAR versus the different parameters was reconstructed for different types of radiofrequency pulses. A Monte Carlo calculation was then performed to compute the probability of occurrence of a given SAR value. RESULTS: By testing a large number of radiofrequency excitation pulses, the SAR calculated for the average model amplified by a safety margin of 1.5 was found to return a probability of less than 1% to be exceeded across the adult Caucasian population given the investigated parameters. CONCLUSION: The proposed method to study SAR intersubject variability uses a reasonable number of electromagnetic simulations. Look-ahead SAR safety margins can be deduced based on risk/benefit ratio assessments. Magn Reson Med 78:1217-1223, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27670738 TI - Transforming Health Care Through Interprofessional Graduate Education. AB - PURPOSE: We provide an overview of the Recovery-based Interprofessional Distance Education (RIDE) rotation for graduate students in psychiatric mental health (PMH) nursing, pharmacy, nutrition, and exercise physiology, with faculty from the four professions represented. CONCLUSIONS: Interprofessional education can enhance team concepts in these professions and is viewed positively by students and faculty. PRACTICE IMPLICATIONS: Interprofessional learning opportunities prepare graduates to contribute to team-based care. We urge colleagues to join us in providing meaningful IPE experiences to students at all levels, with the goal of optimizing health care for all persons with mental health treatment needs. PMID- 27670739 TI - High throughput cell-based assay for identification of glycolate oxidase inhibitors as a potential treatment for Primary Hyperoxaluria Type 1. AB - Glycolate oxidase (GO) and alanine:glyoxylate aminotransferase (AGT) are both involved in the peroxisomal glyoxylate pathway. Deficiency in AGT function causes the accumulation of intracellular oxalate and the primary hyperoxaluria type 1 (PH1). AGT enhancers or GO inhibitors may restore the abnormal peroxisomal glyoxylate pathway in PH1 patients. With stably transformed cells which mimic the glyoxylate metabolic pathway, we developed an indirect glycolate cytotoxicity assay in a 1,536-well plate format for high throughput screening. This assay can be used to identify compounds that reduce indirect glycolate-induced cytotoxicity by either enhancing AGT activity or inhibiting GO. A pilot screen of 4,096 known compounds identified two membrane permeable GO inhibitors: dichromate salt and colistimethate. We also developed a GO enzyme assay using the hydrogen peroxide Amplex red reporter system. The IC50 values of potassium dichromate, sodium dichromate, and colistimethate sodium were 0.096, 0.108, and 2.3 MUM in the GO enzyme assay, respectively. Further enzyme kinetic study revealed that both types of compounds inhibit GO activity by the mixed linear inhibition. Our results demonstrate that the cell-based assay and GO enzyme assay developed in this study are useful for further screening of large compound libraries for drug development to treat PH1. PMID- 27670740 TI - Sensitivity and specificity of real-time PCR and bacteriological culture for francisellosis in farm-raised Nile tilapia (Oreochromis niloticus L.). AB - Despite the worldwide occurrence of Francisella noatunensis subsp. orientalis (Fno) infection in farmed tilapia, sensitivity and specificity estimates of commonly used diagnostic tests have not been reported. This study aimed to estimate the sensitivity and specificity of bacteriological culture and qPCR to detect Fno infection. We tested 559 fish, sampled from four farms with different epidemiological scenarios: (i) healthy fish in a hatchery free of Fno; (ii) targeted sampling of diseased fish with suggestive external clinical signs of francisellosis during an outbreak; (iii) convenience sampling of diseased and clinically healthy fish during an outbreak; and (iv) sampling of healthy fish in a cage farm without a history of outbreaks, but with francisellosis reported in other farms in the same reservoir. The qPCR had higher median sensitivity (range, 48.8-99.5%) than culture (range, 1.6-74.4%). Culture had a substantially lower median sensitivity (1.6%) than qPCR (48.8%) to detect Fno in carrier tilapia (farm 4). Median specificity estimates for both tests were >99.2%. The qPCR is the superior test for use in surveillance and monitoring programmes for francisellosis in farmed Nile tilapia, but both tests have high sensitivity and specificity which make them fit for use in the diagnosis of Fno outbreaks. PMID- 27670741 TI - Global changes in soil stocks of carbon, nitrogen, phosphorus, and sulphur as influenced by long-term agricultural production. AB - Quantifying changes in stocks of C, N, P, and S in agricultural soils is important not only for managing these soils sustainably as required to feed a growing human population, but for C and N, they are also important for understanding fluxes of greenhouse gases from the soil environment. In a global meta-analysis, 102 studies were examined to investigate changes in soil stocks of organic C, total N, total P, and total S associated with long-term land-use changes. Conversion of native vegetation to cropping resulted in substantial losses of C (-1.6 kg m-2 , -43%), N (-0.15 kg m-2 , -42%), P (-0.029 kg m-2 , 27%), and S (-0.015 kg m-2 , -33%). The subsequent conversion of conventional cropping systems to no-till, organic agriculture, or organic amendment systems subsequently increased stocks, but the magnitude of this increase (average of +0.47 kg m-2 for C and +0.051 kg m-2 for N) was small relative to the initial decrease. We also examined the conversion of native vegetation to pasture, with changes in C (-11%), N (+4.1%), and P (+25%) generally being modest relative to changes caused by conversion to cropping. The C:N ratio remained relatively constant irrespective of changes in land use, whilst in contrast, the C:S ratio decreased by 21% in soils converted to cropping - this suggesting that biochemical mineralization is of importance for S. The data presented here will assist in the assessment of different agricultural production systems on soil stocks of C, N, P, and S - this information assisting not only in quantifying the effects of existing agricultural production on these stocks, but also allowing for informed decision-making regarding the potential effects of future land-use changes. PMID- 27670742 TI - Curing the historically incurable: treatment success with ledipasvir/sofosbuvir for chronic hepatitis C virus in a heavily treatment-experienced individual. AB - WHAT IS KNOWN AND OBJECTIVE: Significant progression in the treatment of chronic hepatitis C virus has been made with the introduction of direct-acting antivirals (DAAs). However, limited data are available for the retreatment of individuals who have failed multiple prior DAAs. CASE DESCRIPTION: We report a single case of an individual who was unsuccessfully treated with five prior hepatitis C virus treatment regimens including simeprevir plus sofosbuvir who was successfully cured after treatment with ledipasvir/sofosbuvir. WHAT IS NEW AND CONCLUSION: Ledipasvir/sofosbuvir may be an option for treating patients who have failed multiple prior DAA regimens; however, further research is warranted. PMID- 27670743 TI - Genetic variant in DICER gene is associated with prognosis of hepatocellular carcinoma in a Chinese cohort. AB - AIM: MicroRNAs (miRNAs) function as gene regulators and play crucial roles in the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Genetic variants in miRNA processing genes may affect miRNA expression and contribute to HCC risk and survival. We hypothesized that single nucleotide polymorphisms (SNPs) in miRNA processing genes may be associated with HCC susceptibility and prognosis. The study aims to verify whether this hypothesis is right or not. METHODS: We first genotyped the selected three SNPs in miRNA processing genes (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) in 312 HCC patients and 320 cancer free controls using the TaqMan assay, and evaluated the associations of the three SNPs with HCC risk. We also investigated the effect of the three SNPs on the overall survival of 312 HCC patients. RESULTS: There were no significant associations between the three SNPs (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) and HCC risk. However, HCC patients carrying DICER rs1057035 CT + CC genotypes had significantly longer median survival time (log-rank, P = 0.018) and decreased death risk (adjusted hazard ratio = 0.68; 95% confidence interval, 0.49-0.95; P = 0.022) than patients with rs1057035 TT genotypes. The DICER rs1057035 genotype was an independent protective factor for HCC survival (CT + CC vs. TT: hazard ratio = 0.72; 95% confidence interval, 0.55-0.96; P = 0.031). CONCLUSION: This study provides evidence that DICER rs1057035 T>C polymorphism may be a prognostic biomarker for HCC patients. PMID- 27670744 TI - The cultural beliefs of Jordanian women during childbearing: implications for nursing care. AB - AIMS: To determine the cultural and religious beliefs and practices about childbirth among Jordanian women and to indicate how these beliefs and practices can be integrated into the maternity care of Muslim women in general, especially those immigrating to Western countries. BACKGROUND: The physiology of childbirth is similar for all women worldwide, but the surroundings in which it takes place makes it a unique experience for each woman. Every society has cultural practices and beliefs related to childbirth, and what is considered to be a vital practice in one culture may be seen as insignificant in another. METHODS: A qualitative research design with an interpretative phenomenological approach was used to conduct semi-structured, audiotaped interviews with nine Jordanian mothers. RESULTS: Five main themes identified: childbearing is a blessing of Allah, a time for special maternal care, a time for maternal self-renewal, a time for maternal spiritual purification and a time to prepare for the sacrifices of motherhood. DISCUSSION: The findings reflected the sensitivity of the grace of God in all the interviews, illustrating the permeating influence of religious beliefs on traditional Jordanian childbirth practices. POLICY IMPLICATIONS: In planning policies, health services globally should acknowledge the diverse need of migrant women during childbirth, in order to gain women's trust in maternity services. To offer sensitive care, nurses need to address mothers' cultural and spiritual needs and meet these needs respectfully. CONCLUSIONS: To improve the childbearing experience, maternity staff should consider these themes to help build trust with mothers based on an appreciation of their spiritual and cultural beliefs. PMID- 27670745 TI - Molluscum Contagiosum: A Rare Nipple Lesion. PMID- 27670747 TI - Measuring child personality when child personality was not measured: Application of a thin-slice approach. AB - Recent efforts have demonstrated that thin-slice (TS) assessment-or assessment of individual characteristics after only brief exposure to that individual's behaviour-can produce reliable and valid measurements of child personality traits. The extent to which this approach can be generalized to archival data not designed to measure personality, and whether it can be used to measure personality pathology traits in youth, is not yet known. Archival video data of a parent-child interaction task was collected as part of a clinical intervention trial for aggressive children (N = 177). Unacquainted observers independently watched the clips and rated children on normal-range (neuroticism, extraversion, agreeableness, conscientiousness and openness to experience) and pathological (callous-unemotional) personality traits. TS ratings of child personality showed strong internal consistency, valid associations with measures of externalizing problems and temperament, and revealed differentiated subgroups of children based on severity. As such, these findings demonstrate an ecologically valid application of TS methodology and illustrate how researchers and clinicians can extend their existing data by measuring child personality using TS methodology, even in cases where child personality was not originally measured. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27670746 TI - Bartonella quintana lipopolysaccharide (LPS): structure and characteristics of a potent TLR4 antagonist for in-vitro and in-vivo applications. AB - The pattern recognition receptor TLR4 is well known as a crucial receptor during infection and inflammation. Several TLR4 antagonists have been reported to inhibit the function of TLR4. Both natural occurring antagonists, lipopolysaccharide (LPS) from Gram-negative bacteria as well as synthetic compounds based on the lipid A structure of LPS have been described as potent inhibitors of TLR4. Here, we have examined the characteristics of a natural TLR4 antagonist, isolated from Bartonella quintana bacterium by elucidating its chemical primary structure. We have found that this TLR4 antagonist is actually a lipooligosaccharide (LOS) instead of a LPS, and that it acts very effective, with a high inhibitory activity against triggering by the LPS-TLR4 system in the presence of a potent TLR4 agonist (E. coli LPS). Furthermore, we demonstrate that B. quintana LPS is not inactivated by polymyxin B, a classical cyclic cationic polypeptide antibiotic that bind the lipid A part of LPS, such as E. coli LPS. Using a murine LPS/D-galactosamine endotoxaemia model we showed that treatment with B. quintana LPS could improve the survival rate significantly. Since endogenous TLR4 ligands have been associated with several inflammatory- and immune-diseases, B. quintana LPS might be a novel therapeutic strategy for TLR4 driven pathologies. PMID- 27670748 TI - Tracking the Fate of Surface Plasmon Resonance-Generated Hot Electrons by In Situ SERS Surveying of Catalyzed Reaction. AB - Plasmonic catalysis is an emerging process that utilizes surface plasmon resonance (SPR) process to harnesses solar energy for the promotion of catalyzed reactions. In most cases, SPR generated hot electrons (HEs) play an indispensable role in this solar-chemical energy shift process. Therefore, understanding the effectiveness of the HEs in promoting chemical reactions, and identifying the key factors that contribute to this utilization efficiency is of profound importance. Herein, the authors outline an in situ surface enhanced Raman spectroscopy protocol to track the fate of HEs. This is based on the unheeded HEs-acceleration nature of the p-nitirothiophenol hydrogenation reaction. By this way, the authors discover that unlike Au@Pd nanostructures which experience a 20-fold increase in rate constant, HEs primary leak to surrounding H+ /O species through Ag pinholes in Ag@Pd. This work sheds light on why Ag is seldom employed as a plasmonic cocatalyst, and provides a new viewpoint to design plasmonic nanocatalysts with efficient light utilization. PMID- 27670749 TI - Effervescence-assisted dispersive solid-phase extraction using ionic-liquid modified magnetic beta-cyclodextrin/attapulgite coupled with high-performance liquid chromatography for fungicide detection in honey and juice. AB - In this study, a simple effervescence-assisted dispersive solid-phase extraction method was developed to detect fungicides in honey and juice. Most significantly, an innovative ionic-liquid-modified magnetic beta-cyclodextrin/attapulgite sorbent was used because its large specific surface area enhanced the extraction capacity and also led to facile separation. A one-factor-at-a-time approach and orthogonal design were employed to optimize the experimental parameters. Under the optimized conditions, the entire extraction procedure was completed within 3 min. In addition, the calibration curves exhibited good linearity, and high enrichment factors were achieved for pure water and honey samples. For the honey samples, the extraction efficiencies for the target fungicides ranged from 77.0 to 94.3% with relative standard deviations of 2.3-5.44%. The detection and quantitation limits were in the ranges of 0.07-0.38 and 0.23-1.27 MUg/L, respectively. Finally, the developed technique was successfully applied to real samples, and satisfactory results were achieved. This analytical technique is cost-effective, environmentally friendly, and time-saving. PMID- 27670750 TI - Determination of isocyanate groups in the organic intermediates by reaction-based headspace gas chromatography. AB - This work reports on a novel method for the determination of isocyanate groups in the related organic intermediates by a reaction-based headspace gas chromatography. The method is based on measuring the CO2 formed from the reaction between the isocyanate groups in the organic intermediates and water in a closed headspace sample vial at 45 degrees C for 20min. The results showed that the method has a good precision and accuracy, in which the relative standard deviation in the repeatability measurement was 5.26%, and the relative differences between the data obtained by the HS-GC method and the reference back titration method were within 9.42%. The present method is simple and efficient and is particularly suitable to be used for determining the isocyanate groups in the batch sample analysis. PMID- 27670751 TI - Assessment of antioxidant activity in Victorian marine algal extracts using high performance thin-layer chromatography and multivariate analysis. AB - The aim of this study was to develop and validate a rapid and simple high performance thin layer chromatographic (HPTLC) method to screen for antioxidant activity in algal samples. 16 algal species were collected from local Victorian beaches. Fucoxanthin, one of the most abundant marine carotenoids was quantified directly from the HPTLC plates before derivatization, while derivatization either with 2,2-diphenyl-1-picrylhydrazyl (DPPH) or ferric chloride (FeCl3) was used to analyze antioxidants in marine algae, based on their ability to scavenge non biological stable free radical (DPPH) or to chelate iron ions. Principal component analysis of obtained HPTLC fingerprints has classified algae species into 5 groups according to their chemical/antioxidant profiles. The investigated brown algae samples were found to be rich in non-and moderate-polar compounds and phenolic compounds with antioxidant activity. Most of the phenolic iron chelators also have shown free radical scavenging activity. Strong positive and significant correlations between total phenolic content and DPPH radical scavenging activity showed that, phenolic compounds, including flavonoids are the main contributors of antioxidant activity in these species. The results suggest that certain brown algae possess significantly higher antioxidant potential when compared to red or green algae and could be considered for future applications in medicine, dietary supplements, cosmetics or food industries. Cystophora monilifera extract was found to have the highest antioxidant concentration, followed by Zonaria angustata, Cystophora pectinate, Codium fragile, and Cystophora pectinata. Fucoxanthin was found mainly in the brown algae species. The proposed methods provide an edge in terms of screening for antioxidants and quantification of antioxidant constituents in complex mixtures. The current application also demonstrates flexibility and versatility of a standard HPTLC system in the drug discovery. Proposed methods could be used for the bioassay-guided isolation of unknown natural antioxidants and subsequent identification if combined with spectroscopic identification. PMID- 27670752 TI - Preparation of salvianolic acid A by the degradation reaction of salvianolic acid B in subcritical water integrated with pH-zone-refining counter-current chromatography. AB - Salvianolic acid A is the major bioactive compound in Danshen, however, due to the chemical instability and low content in Danshen, it is difficult to extract amount of salvianolic acid A. Therefore, this study was to establish an effective strategy for obtaining adequate amount of salvianolic acid A, subcritical water extraction was used to degrade salvianolic acid B and prepare salvianolic acid A. Different reaction conditions including temperature, time, concentration and pH value in subcritical water were investigated. Under 40mg/mL of reactant concentration, 180 degrees C of temperature, 4.0 of pH value and 60min of reaction time, the highest yield rate of salvianolic acid A reached 34.86%. Then, the degradation products were successfully separated by pH-zone-refining counter current chromatography with the solvent system Pet-EtAc-n-BuOH-H2O (2:3:1:9, v/v), where 10mM TFA was added in stationary phase and 10mM NH3.H2O in mobile phase. As a result, a total of 227.3mg of salvianolic acid A at 98.2% purity, 38.9mg of danshensu at 99.3% purity, 9.5mg of salvianolic acid D at 92.7% purity, and 32.8mg of protocatechuic aldehyde at 93.1% purity were obtained from 1.2g degradation products of salvianolic acid B by one-step purification. The results demonstrated that the combinative application of subcritical water and pH-zone refining counter-current chromatography is a potential technique for the preparative separation of salvianolic acid A from salvianolic acid B. PMID- 27670753 TI - In honour of Professor Pieter R Cullis, recipient of the Journal of Drug Targeting's Lifetime Achievement Award for 2016. PMID- 27670754 TI - Co-stimulation of HaCaT keratinization with mechanical stress and air-exposure using a novel 3D culture device. AB - Artificial skin or skin equivalents have been used for clinical purpose to skin graft and as substitutes for animal experiments. The culture of cell lines such as HaCaT has the potential to produce large amounts of artificial skin at a low cost. However, there is a limit to keratinization due to the restriction of differentiation in HaCaT. In this study, a culture device that mimics the in vivo keratinization mechanism, co-stimulated by air-exposure and mechanical stimulation, was developed to construct skin equivalents. The device can reconstruct the epidermal morphology, including the cornified layer, similar to its formation in vivo. Under the condition, epidermis was differentiated in the spinous and granular layers. Formation of the stratum corneum is consistent with the mRNA and protein expressions of differentiation markers. The device is the first of its kind to combine air-exposure with mechanical stress to co-stimulate keratinization, which can facilitate the economically viable production of HaCaT based artificial skin substitutes. PMID- 27670755 TI - A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway. Patient and prescriber characteristics, and dispense patterns. A drug utilization cohort study. AB - PURPOSE: Following a TV documentary in 2013, there was a tremendous increase in low dose naltrexone (LDN) use in a wide range of unapproved indications in Norway. We aim to describe the extent of this sudden and unprecedented increase in LDN prescribing, to characterize patients and LDN prescribers, and to estimate LDN dose sizes. METHODS: LDN prescriptions recorded in the Norwegian Prescription Database (NorPD) in 2013 and 2014, and sales data not recorded in NorPD from the only Norwegian LDN manufacturer were included in the study. RESULTS: According to NorPD, 15 297 patients (0.3% of population) collected at least one LDN prescription. The actual number of users was higher as at least 23% of total sales were not recorded in NorPD. After an initial wave, there was a steady stream of new and persistent users throughout the study period. Median patient age was 52 years, and 74% of patients were female. Median daily dose was 3.7 mg. Twenty percent of all doctors and 71% of general medicine practitioners registered in Norway in 2014 prescribed LDN at least once. CONCLUSIONS: The TV documentary on LDN in Norway was followed by a large increase in LDN prescribing, and the proportion of LDN users went from an insignificant number to 0.3% of the population. There was a high willingness to use and prescribe off label despite limited evidence. Observed median LDN dose, and age and gender distribution were as expected in typical LDN using patients. (c) 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. PMID- 27670756 TI - Fire-setting performed in adolescence or early adulthood predicts schizophrenia: a register-based follow-up study of pre-trial offenders. AB - BACKGROUND: Aggressive and disruptive behaviours often precede the onset of serious mental illnesses. Fire-setting is a type of crime that is associated with psychotic disorders. AIM: The aim of this prospective follow-up study was to investigate if fire-setting performed in adolescence or early adulthood was associated with future diagnoses of schizophrenia or schizoaffective disorder. METHODS: The consecutive sample consisted of 111 Finnish 15-25-year old males with fire-setting crimes, decreed to a pre-trial forensic psychiatric examination in 1973-1998, and showing no past nor current psychosis at the time of examination. For each firesetter, four age-, gender-, and place of birth-matched controls were randomly selected from the Central Population Register. The subjects were followed until the death of the individual, until they moved abroad, or until the end of 2012. RESULTS: Fourteen firesetters (12.6%) and five controls (1.1%) were diagnosed with either schizophrenia or schizoaffective disorder later in life, corresponding to a hazard ratio of 12.5. The delay between the fire-setting offense and the future diagnosis was on average nearly 10 years. CONCLUSIONS: Young male offenders undergoing a forensic psychiatric examination because of fire-setting crimes had a significant propensity for schizophrenia and schizoaffective disorder. Accurate assessments should be made both during imprisonment and later in life to detect possible psychotic signs in these individuals. PMID- 27670757 TI - Scaffold-Free Tissue-Engineered Allogenic Adipose-Derived Stem Cells Promote Meniscus Healing. AB - PURPOSE: To determine whether meniscal tissue could be healed histologically by the implantation of allogenic three-dimensional formed adipose-derived stem cells (ADSCs) in a rabbit model of partial meniscectomy. METHODS: Forty Japanese white rabbits (aged 15-17 weeks) were assigned to 2 groups. Defects 1.5 mm in diameter were created in the anterior horn of the medial menisci. The defects were left empty in the control group and were filled with cylindrical plugs of allogenic ADSCs extracted from adipose tissue in the experimental group. Macroscopic scoring (range, 0-3), histological scoring (range, 0-12), and immunohistological stainability of type I collagen were evaluated at 2, 4, 8, and 12 weeks postoperatively (n = 5 rabbits for each week). RESULTS: Macroscopically, the height of the healing tissue in the experimental group was significantly greater than that of the control group at 2 weeks (3 vs 0, P = .01), 4 weeks (3 vs 1, P = .01), and 8 weeks (3 vs 2, P = .02). Histologically, safranin-O staining was noted at 2 weeks and increased gradually over time in the experimental group. In contrast, the intensity of staining was lower in controls at all weeks. Tissue quality scores were significantly higher in the experimental group than in the controls at all weeks (3 vs 0 at 2 weeks [P = .00009], 4.5 vs 2 at 4 weeks [P = .00023], 9 vs 5 at 8 weeks [P = .0047], 10.5 vs 6 at 12 weeks [P = .00026]). The implanted tissue was positive for type I collagen, and stainability was increased gradually over time. CONCLUSIONS: Three-dimensional scaffold-free allogenic ADSCs implanted into a 1.5-mm avascular meniscal defect survived, adhered to the defect, and promoted histological meniscus healing in a rabbit model. CLINICAL RELEVANCE: ADSC implantation designed to promote meniscal healing may play an important role as a tool for meniscus healing. PMID- 27670758 TI - Trackways Produced by Lungfish During Terrestrial Locomotion. AB - Some primarily aquatic vertebrates make brief forays onto land, creating traces as they do. A lack of studies on aquatic trackmakers raises the possibility that such traces may be ignored or misidentified in the fossil record. Several terrestrial Actinopterygian and Sarcopterygian species have previously been proposed as possible models for ancestral tetrapod locomotion, despite extant fishes being quite distinct from Devonian fishes, both morphologically and phylogenetically. Although locomotion has been well-studied in some of these taxa, trackway production has not. We recorded terrestrial locomotion of a 35 cm African lungfish (Protopterus annectens; Dipnoi: Sarcopterygii) on compliant sediment. Terrestrial movement in the lungfish is accomplished by planting the head and then pivoting the trunk. Impressions are formed where the head impacts the substrate, while the body and fins produce few traces. The head leaves a series of alternating left-right impressions, where each impact can appear as two separate semi-circular impressions created by the upper and lower jaws, bearing some similarity to fossil traces interpreted as footprints. Further studies of trackways of extant terrestrial fishes are necessary to understand the behavioural repertoire that may be represented in the fossil track record. PMID- 27670759 TI - Faecal blood testing cuts unnecessary colonoscopies by a third, shows study. PMID- 27670761 TI - T-lymphoid progenitors - we know what they are, but know not what they may be. PMID- 27670762 TI - A comparison of fitting algorithms for diffusion-weighted MRI data analysis using an intravoxel incoherent motion model. AB - OBJECT: The objective of this study is to propose a modified VARiable PROjection (VARPRO) algorithm specifically tailored for fitting the intravoxel incoherent motion (IVIM) model to diffusion-weighted magnetic resonance imaging (DW-MRI) data from locally advanced rectal cancer (LARC). MATERIALS AND METHODS: The proposed algorithm is compared with classical non-linear least squares (NLLS) analysis using the Levenberg-Marquardt (LM) algorithm and with two recently proposed algorithms for 'segmented' analysis. These latter two comprise two consecutive steps: first, a subset of parameters is estimated using a portion of data; second, the remaining parameters are estimated using the whole data and the previous estimates. The comparison between the algorithms was based on the [Formula: see text] goodness-of-fit measure: performance analysis was carried out on real data obtained by DW-MRI on 40 LARC patients. RESULTS: The performance of the proposed algorithm was higher than that of LM in 64 % of cases; 'segmented' methods were poorer than our algorithm in 100 % of cases. CONCLUSION: The proposed modified VARPRO algorithm can lead to better fit of the IVIM model to LARC DW-MRI data compared to other techniques. PMID- 27670760 TI - Membrane fission by dynamin: what we know and what we need to know. AB - The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion. PMID- 27670763 TI - TREM1 facilitates microglial phagocytosis of amyloid beta. AB - As the most common type of neurodegenerative disease, Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta peptide (Abeta) within the brain. Triggering receptor expressed on myeloid cells (TREM) 1 is an immune receptor expressed by mononuclear phagocytes including monocytes and microglia, coupling with TYRO protein tyrosine kinase binding protein to regulate immune reactions. Emerging evidence indicates that rs6910730G, an intronic variant of TREM1, is associated with an increased Abeta neuropathology in the brains of elderly subjects, but the underlying mechanisms remain unclear. Here, using two independent cohorts of healthy individuals, we provided evidence that rs6910730G reduced the ability of human monocytes for Abeta phagocytosis, and this reduction was likely attributed to a decreased monocytic TREM1 expression. By knockdown and overexpression of Trem1 in mouse primary microglia, we showed that TREM1 facilitated microglial phagocytosis of Abeta. In support of this finding, knockdown of Trem1 in the brains of APP/PSEN1 mice increased Abeta1-42 levels and total amyloid burden, whereas selective overexpression of Trem1 on microglia or activation of Trem1 signaling by an agonistic antibody ameliorated Abeta neuropathology and rescued AD-related spatial cognitive impairments. Altogether, these findings uncover the role of TREM1 in microglial Abeta clearance, and establish TREM1 as a potential therapeutic target for AD. PMID- 27670764 TI - A preliminary study of the role of extracellular -5'- nucleotidase in breast cancer stem cells and epithelial-mesenchymal transition. AB - Tumor stem cell theory may well explain a variety of malignant behaviors of tumors. Cells undergoing epithelial-mesenchymal transition (EMT) share many characteristics with tumor stem cells. Our previous studies showed that extracellular -5'- nucleotidase (CD73), one of the important surface markers of mesenchymal stem cells, may promote growth and metastasis of breast cancer cells both in vivo and in vitro. In this study, we assessed breast cancer stem cell (BCSC) markers [acetaldehyde dehydrogenase (ALDH)+ and CD44+CD24-] in various breast cancer cell lines with flow cytometry after overexpression (by lentivirus infection) or suppression (by siRNA interference) of CD73. We measured CD73 expression in breast cancer mammospheres with real-time PCR and western blots. Finally, we examined the expression of CD73 and EMT markers in different breast cancer cell lines, as well as in mammary cells (MCF10A) that underwent EMT induced by transforming growth factor beta (TGF-beta). We found that CD73 positively correlated with ALDH+ or CD44+CD24- subsets of breast cancer cells. CD73 was expressed more in breast cancer mammospheres than in adherent cells. CD73 and mesenchymal marker expression was higher in breast cancer cells with more malignant features, while CD73 was lower in low malignant breast cancer cells with higher epithelial markers. Furthermore, CD73 expression increased during the process of TGF-beta-induced EMT. Our results indicate that CD73 may play an important role in BCSCs. PMID- 27670765 TI - New polymorphisms associated with response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis. AB - Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20-30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice. PMID- 27670766 TI - IL17RA gene variants and anti-TNF response among psoriasis patients. AB - Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05 3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12. PMID- 27670768 TI - Genes differentially expressed by methylprednisolone in vivo in CD4 T lymphocytes from multiple sclerosis patients: potential biomarkers. AB - Intravenous methylprednisolone (IVMP) is the gold standard treatment in acute relapses of multiple sclerosis. Knowing the response to IVMP in advance could facilitate earlier selection of patients for subsequent courses of therapy. However, molecular mechanisms and changes in gene expression induced by methylprednisolone remain unknown. The aim of the study was to identify in vivo differentially expressed genes in relapsing-remitting multiple sclerosis patients after 3-6 days of treatment with IVMP. For this purpose, whole-genome transcription profiling of CD4+ T lymphocytes was performed before and after treatment with IVMP in 8 relapsing-remitting multiple sclerosis patients during relapse using Human GE 4x44K v2 microarrays. Differentially expressed genes were identified using a paired t test on GeneSpring v13.0 software. A P-value <0.001 and a twofold change were considered significant. Microarray data were confirmed using real-time PCR. Microarray revealed changes in gene expression: four genes were downregulated (B3GNT3, ZNF683, IFNG and TNF) and seven upregulated (DEFA4, CTSG, DEFA8P, AZU1, MPO, ELANE and PRTN3). Pathway analysis revealed the transforming growth factor-beta signaling pathway to be affected. Comparison with previously published data on in vitro methylprednisolone-regulated genes showed that SMAD7, TNF and CHI3L1 were also downregulated in vivo in relapsing-remitting multiple sclerosis patients. In summary, we performed the first in vivo transcriptome analysis in CD4+ T lymphocytes before and after the treatment with IVMP in patients with multiple sclerosis. Identification of differentially expressed genes in patients receiving IVMP could improve our understanding of the molecular mechanisms underlying the therapeutic effects of IVMP and highlight potential biomarkers of the response to IVMP. PMID- 27670767 TI - Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes. AB - We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a beta-blocker-based strategy (beta-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis P=5.3 * 10-8). rs11124945 G allele carriers had lower odds for NOD when exposed to the beta-blocker strategy compared with the CCB strategy (Odds ratio OR=0.38(0.24-0.60), P=4.0 * 10-5), whereas A/A homozygotes exposed to the beta-blocker strategy had increased odds for NOD compared with the CCB strategy (OR=2.02(1.39-2.92), P=2.0 * 10-4). eQTL annotation of the 2p21 locus provides functional support for regulating gene expression. PMID- 27670770 TI - Code Saturation Versus Meaning Saturation: How Many Interviews Are Enough? AB - Saturation is a core guiding principle to determine sample sizes in qualitative research, yet little methodological research exists on parameters that influence saturation. Our study compared two approaches to assessing saturation: code saturation and meaning saturation. We examined sample sizes needed to reach saturation in each approach, what saturation meant, and how to assess saturation. Examining 25 in-depth interviews, we found that code saturation was reached at nine interviews, whereby the range of thematic issues was identified. However, 16 to 24 interviews were needed to reach meaning saturation where we developed a richly textured understanding of issues. Thus, code saturation may indicate when researchers have "heard it all," but meaning saturation is needed to "understand it all." We used our results to develop parameters that influence saturation, which may be used to estimate sample sizes for qualitative research proposals or to document in publications the grounds on which saturation was achieved. PMID- 27670769 TI - Estrogen-like neuroprotection of isopsoralen against spinal cord injury through estrogen receptor ERalpha. AB - Isopsoralen is a type of furocoumarin that exhibits estrogen-like activities. The aim of this study was to determine the estrogen-like neuroprotection of isopsoralen in an animal model of spinal cord injury (SCI). Results indicated that isopsoralen (intraperitoneal injection of 5 and 10 mg/kg per day for two weeks) significantly enhanced the hindlimb locomotor functions of mice with SCI, as revealed in the BMS score and angle of inclined plane tests. Morphological data showed that isopsoralen significantly attenuated the injury of the gray matter of spinal cord and induced the up-regulation of ERalpha levels. The neuroprotective effects of isopsolaren were blocked by the ERalpha antagonist MPP (0.3 mg/kg), but not by the ERbeta receptor antagonist PHTPP (0.3 mg/kg). Isopsolaren treatment increased phosphorylated PI3K and AKT (P-PI3K and P-AKT) in the spinal cord of SCI mice and showed a significant anti-apoptotic activity. These results suggest that isopsoralen performs estrogen-like neuroprotection against SCI-induced apoptosis by activating ERalpha and regulating the PI3K/AKT pathway. PMID- 27670772 TI - Description of a Novel Monopartite Geminivirus and Its Defective Subviral Genome in Grapevine. AB - A novel virus was detected in grapevines by Illumina sequencing during the screening of two table grape (Vitis vinifera) accessions, cultivars Black Beet and Nagano Purple, from South Korea. The monopartite circular ssDNA genome sequence was subsequently confirmed by rolling cycle amplification, cloning and Sanger sequencing. The complete viral genomic sequence from both accessions ranged from 2,903 to 2,907 nucleotides in length and contained the conserved nonanucleotide sequence TAATATT?AC and other sequence features typical of the family Geminiviridae, including two predicted sense and four complementary-sense open reading frames. Phylogenetic analysis placed the novel virus in a unique taxon within the family Geminiviridae. A naturally occurring defective subviral DNA was also discovered. This defective DNA molecule carried a deletion of approximately 46% of the full-length genome. Both the genomic and defective DNA molecules were graft-transmissible although no disease is yet correlated with their occurrence in Vitis spp. The tentative names Grapevine geminivirus A (GGVA) and GGVA defective DNA (GGVA D-DNA) are proposed. PCR assays developed using primers designed in the coat protein gene led to the detection of GGVA in 1.74% of 1,262 vines derived from 15 grapevine cultivars from six countries across three continents. PMID- 27670773 TI - Predictors of Smoking Cessation and Relapse in Cancer Patients and Effect on Psychological Variables: an 18-Month Observational Study. AB - BACKGROUND: Although cancer patients are generally strongly advised to quit smoking in order to improve treatment efficacy and survival, up to 68 % of patients who were smokers at the time of cancer diagnosis continue smoking. Psychological factors such as depression and anxiety are likely to be associated with smoking behavior following a cancer diagnosis, but the empirical evidence is scarce. PURPOSE: This observational study aimed at estimating smoking cessation rates and assessing the effect of smoking cessation on psychological symptoms, as well as the predictive role of the same psychological variables on smoking cessation and smoking relapse following cancer surgery. METHODS: As part of a larger prospective, epidemiological study, smokers (n = 175) with a first diagnosis of nonmetastatic cancer completed the Hospital Anxiety and Depression Scale, the Insomnia Severity Index, and the Fear of Cancer Recurrence Inventory. Quitters (n = 55) and pair-matched nonquitters (n = 55) were compared on each symptom at pre-quitting, post-quitting, and at a 4-month follow-up. Predictors of smoking cessation and smoking relapse, including psychological variables, were also investigated. RESULTS: Fifty-five patients (31.4 %) stopped smoking at least on one occasion during the study. Of the 55 quitters, 27 (49.1 %) experienced a relapse. At pre-quitting, quitters had significantly higher levels of anxiety (p = .03) and fear of cancer recurrence (p = .01) than nonquitters, symptoms that significantly diminished at post-quitting and 4 months later in this subgroup of patients. Having breast cancer significantly predicted smoking cessation (relative risk [RR] = 3.08), while depressive symptoms were a significant predictor of smoking relapse (RR = 1.07). CONCLUSIONS: This study highlights the importance of psychological symptoms in predicting tobacco cessation and relapse among individuals with cancer. Our findings suggest that breast cancer patients are more inclined to stop smoking than patients with other cancers, but future studies should attempt to delineate the effect on smoking cessation of gender and other demographics that characterize this subgroup. This study also suggests that a particular attention should be paid to the early management of depressive symptoms in order to prevent smoking relapse. PMID- 27670774 TI - Exposure factors of cadmium for residents in an abandoned metal mine area in Korea. AB - This study evaluated blood and urine cadmium (Cd) levels and human exposure factors for residents in an abandoned metal mine in Korea. We collected blood, urine, soil, water, and rice grain samples to analyze Cd concentrations and analyzed heavy metal concentration patterns in soil. We estimated the major exposure factor of Cd through non-carcinogenic risk assessment depending on exposure routes. The blood Cd concentration in the case group was 5.33 MUg/L (geometric mean), significantly higher than that in the control group (1.63 MUg/L, geometric mean). Urine Cd concentrations were also similar. The Cd concentrations in paddy soil (1.29 mg/kg) and rice grains (0.14 mg/kg) in the study area were higher than those in the control area (0.91 and 0.07 mg/kg, respectively). The analysis of heavy metal concentration in soil showed that the Cd levels in agricultural soil in the case group were attributable to the mine. The hazard quotient (HQ) of Cd by rice ingestion in the case group (1.25) was 2 times higher than that in the control group (0.6). We found that the HQ of rice ingestion contributed to more than 97 % of the total HQ, indicating that rice grains were the major exposure source. However, it is likely that the continuous intake of Cd-exposed crops led to chronic exposure among the residents in mine area. PMID- 27670776 TI - Social cognitive interventions for people with schizophrenia: A systematic review. AB - Social cognition is the mental process which underpins social interactions. Increasingly, it has been recognized to be impaired in people with schizophrenia, resulting in functional problems. Correspondingly, the past ten years have seen huge developments in the study of interventions to ameliorate social cognitive deficits among people with schizophrenia. In the present review, we systematically reviewed published studies on social cognitive interventions from 2005 to 2015. Of the 61 studies included in this review, 20 were on broad-based social cognitive interventions, which incorporated neurocognitive training, specialized learning technique or virtual reality social skills training. On the other hand, 31 studies on targeted interventions either focused on specific social cognitive domains, or a range of domains. Improvements in emotion processing and theory of mind were often reported, while social perception and attributional style were less frequently measured. Both broad-based and targeted interventions achieved gains in social functioning, albeit inconsistently. Lastly, nine studies on the use of oxytocin and one study on transcranial direct current stimulation reported positive preliminary results in higher-order cognition and facial affect recognition respectively. This review revealed that a wide range of social cognitive interventions is currently available and most have shown some promise in improving social cognition outcomes. However, there is a need to use a common battery of measurements for better comparisons across interventions. Future research should examine combination therapies and the sustainability of gains beyond the intervention period. PMID- 27670775 TI - Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor. AB - Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIbalpha subunit of GPIb-IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane 'Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb-IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors. PMID- 27670777 TI - FAMSA: Fast and accurate multiple sequence alignment of huge protein families. AB - Rapid development of modern sequencing platforms has contributed to the unprecedented growth of protein families databases. The abundance of sets containing hundreds of thousands of sequences is a formidable challenge for multiple sequence alignment algorithms. The article introduces FAMSA, a new progressive algorithm designed for fast and accurate alignment of thousands of protein sequences. Its features include the utilization of the longest common subsequence measure for determining pairwise similarities, a novel method of evaluating gap costs, and a new iterative refinement scheme. What matters is that its implementation is highly optimized and parallelized to make the most of modern computer platforms. Thanks to the above, quality indicators, i.e. sum-of pairs and total-column scores, show FAMSA to be superior to competing algorithms, such as Clustal Omega or MAFFT for datasets exceeding a few thousand sequences. Quality does not compromise on time or memory requirements, which are an order of magnitude lower than those in the existing solutions. For example, a family of 415519 sequences was analyzed in less than two hours and required no more than 8 GB of RAM. FAMSA is available for free at http://sun.aei.polsl.pl/REFRESH/famsa. PMID- 27670778 TI - Multifunctional Reversible Fluorescent Controller Based on a One-Dimensional Photonic Crystal. AB - With the aim to build a multifunctional solid fluorescent controller, a one dimensional photonic crystal and CdSe fluorescent single layer were separated on the opposite sides of quartz substrates. The separation structure remarkably facilitates materials selection for the fluorescent controller, which allows one to freely choose the fluorescent substance and constituents of 1DPC from a wide range of available materials with the best desirable properties and without caring about the interactions between them. Fluorescent enhancement and weakened effect were successfully achieved when the excitation light was irradiated from different sides of the fluorescent device. In addition, the fluorescent intensity can be altered reversibly along with environmental pH values according to the change of a pH-responsive one-dimensional photonic crystal layer, which is quite different from a previously reported quenching mode. Meanwhile, the original position of the photonic stop band is essential for deciding what pH value would produce the best effect of fluorescent control. It provides a way to adjust the effect of fluorescent controller according to certain applied situations. The mechanism of fluorescent variation was confirmed by the assistance of a finite difference time-domain simulation. Furthermore, this device is also able to modulate fluorescent wavelength and full width at half-maximum by overlapping the photonic stop band and the emission of CdSe. Therefore, this method offers a universal strategy for the fabrication of fluorescent controllers. PMID- 27670779 TI - Targeting Neovasculature with Multitargeted Antiangiogenesis Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer. AB - Chemotherapy has reached a plateau in the efforts for survival improvement in non small cell lung cancer (NSCLC). The growing knowledge of NSCLC molecular pathobiology has led to the development of new treatments that target specific tumor functions. Angiogenesis is a tumor function leading to the formation of new tumor vessels that are crucial for its survival. Although vascular endothelial growth factor (VEGF) plays a primary role in angiogenesis, the inhibition of the VEGF pathway with VEGF-receptor (VEGFR) tyrosine kinase inhibitors (TKIs) is associated with a modest survival benefit due to the development of resistance by the tumor that has been mainly attributed to the up-regulation of other stimulators of angiogenesis. Thus, the use of multitargeted antiangiogenesis TKIs (MATKIs) for simultaneous inhibition of multiple angiogenic pathways has been proposed. This review summarizes data about novel treatment strategies incorporating the inhibition of angiogenesis with MATKIs in NSCLC. The data from all relevant studies shows that MATKIs do not offer additional survival benefit to currently available chemotherapeutic options in unselected NSCLC patients. However, the diversity in disease response to MATKI-containing regimens implies that specific patient subgroups may benefit from or be harmed by these agents. In this context, most studies agree that the VEGFR-targeting MATKIs are harmful in squamous NSCLC while specific MATKIs (i.e., motesanib, vandetanib and nintedanib) are associated with improved progression free survival in non-squamous NSCLC. However, overall survival benefit was found only in adenocarcinoma and Asian non squamous NSCLC patients with the use of nintedanib and motesanib, respectively. PMID- 27670780 TI - Persistently high prevalence of primary resistance and multidrug resistance of tuberculosis in Heilongjiang Province, China. AB - BACKGROUND: The spread of multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has been a big challenge to the TB control and prevention in China. Knowledge about patterns of drug resistance in TB high burden areas of China is crucial to develop appropriate control strategies. We conducted a comprehensive investigation of the resistance pattern of M. tuberculosis in Heilongjiang Province. METHODS: 1427 M. tuberculosis clinical strains were isolated from pulmonary TB patients hospitalized between 2007 and 2012. The susceptibility of the isolates to the first-line anti-TB drugs and the resistance of MDR M. tuberculosis to fluoroquinolones were examined. We also performed a statistical analysis to identify the correlated risk factors for high burden of MDR-TB. RESULTS: The global resistance rates of 2007-2012 to the first line drugs and MDR were 57.0 and 22.8 %, respectively. Notably, the primary MDR TB and pan-resistance rates were as high as 13.6 and 5.0 %, respectively. Of MDR M. tuberculosis isolates (2009), approximately 13 % were not susceptible to any of the fluoroquinolones tested. Being age of 35 to 54, high re-treatment proportion, the presence of cavity lesion, and high proportion of shorter hospitalization are correlated with the development of MDR-TB. CONCLUSIONS: The high prevalence of drug resistant, MDR-TB, and fluoroquinolone-resistant MDR-TB is a big concern for TB control. More importantly, in order to control the development of MDR-TB effectively, we need to pay more attention to the primary resistance. Targeting reducing the prevalence of the risk factors may lead to better TB control in China. PMID- 27670782 TI - Differences in procedural knowledge after a "spaced" and a "massed" version of an intensive course in emergency medicine, investigating a very short spacing interval. AB - BACKGROUND: Distributing a fixed amount of teaching hours over a longer time period (spaced approach) may result in better learning than delivering the same amount of teaching within a shorter time (massed approach). While a spaced approach may provide more opportunities to elaborate the learning content, a massed approach allows for more economical utilisation of teaching facilities and to optimise time resources of faculty. Favourable effects of spacing have been demonstrated for postgraduate surgery training and for spacing intervals of weeks to months. It is however unknown, whether a spacing effect can also be observed for shorter intervals and in undergraduate medical education. Therefore, we aimed to evaluate the effect of a short spacing intervention within an undergraduate intensive course in emergency medicine (EM) on students' procedural knowledge. METHODS: An EM intensive course of 26 teaching hours was delivered over either 4.5 days, or 3.0 days. After the course students' procedural knowledge was assessed by a specifically developed video-case based key-feature test (KF-test). RESULTS: Data sets of 156 students (81.7 %, 191 students eligible) were analysed, 54 from the spaced, and 102 from the massed version. In the KF-test students from the spaced version reached a mean of 14.8 (SD 2.0) out of 22 points, compared to 13.7 (SD 2.0) in the massed version (p = .002). Effect size was moderate (Cohen's d: 0.558). CONCLUSION: A significant spacing effect was observable even for a short spacing interval in undergraduate medical education. This effect was only moderate and may be weighed against planning needs of faculty and teaching resources. PMID- 27670781 TI - Host cytoskeleton in respiratory syncytial virus assembly and budding. AB - Respiratory syncytial virus (RSV) is one of the major pathogens responsible for lower respiratory tract infections (LRTI) in young children, the elderly, and the immunosuppressed. Currently, there are no antiviral drugs or vaccines available that effectively target RSV infections, proving a significant challenge in regards to prevention and treatment. An in-depth understanding of the host-virus interactions that underlie assembly and budding would inform new targets for antiviral development.Current research suggests that the polymerised form of actin, the filamentous or F-actin, plays a role in RSV assembly and budding. Treatment with cytochalasin D, which disrupts F-actin, has been shown to inhibit virus release. In addition, the actin cytoskeleton has been shown to interact with the RSV matrix (M) protein, which plays a central role in RSV assembly. For this reason, the interaction between these two components is hypothesised to facilitate the movement of viral components in the cytoplasm and to the budding site. Despite increases in our knowledge of RSV assembly and budding, M-actin interactions are not well understood. In this review, we discuss the current literature on the role of actin cytoskeleton during assembly and budding of RSV with the aim to integrate disparate studies to build a hypothetical model of the various molecular interactions between actin and RSV M protein that facilitate RSV assembly and budding. PMID- 27670783 TI - Shorter anogenital and anoscrotal distances correlate with the severity of hypospadias: A prospective study. AB - INTRODUCTION: Anogenital distance (AGD) is a recognised marker of in utero androgen action. OBJECTIVE: This study aimed to evaluate the relationship between severity of hypospadias and AGD. STUDY DESIGN: Boys undergoing hypospadias repair in a single tertiary centre between May 2012 and February 16 were included in the study. Anogenital distance was measured from the centre of the anus to the base of the penis, and anoscrotal distance (ASD) from the centre of the anus to the junction between the smooth perineal skin and scrotal skin. Trained paediatric urologists made all measurements using digital callipers. RESULTS: Fifty-nine boys with hypospadias and 31 age-matched controls undergoing circumcision (median age 1.37 years, range 1.01-1.96) had AGD and ASD measured under anaesthetic. The patients were divided into two groups, according to hypospadias severity: group 1 - distal penile/subcoronal/glandular (n = 40); and group 2 - perineal/penoscrotal/midshaft (n = 19). The median AGD for controls was 74.0 mm (range 53.2-87.8) and for hypospadias it was 72.3 mm (range 50.7-90.0) (P = 0.816). The median ASD for controls was 42.3 mm (range 31.0-56.1) and for hypospadias it was 39.4 mm (range 20.7-77.0) (P = 0.224). Considering severity of hypospadias, the median AGD for group 1 and group 2 was 73.7 mm (range 50.7-90.0) and 63.3 mm (range 53.6-77.0), respectively (P < 0.001). The median ASD was also higher in group 1, at 41.3 mm (range 20.7-65.0), compared to 35.2 mm (range 23.5 77.0) in group 2 (P = 0.119) (Summary Fig.). DISCUSSION: This study showed that more severe forms of hypospadias are associated with shorter AGD and ASD. These findings agree with two previous studies that identified reduced AGD in boys with hypospadias. However, these studies did not investigate an association with severity of hypospadias. As hypospadias is multifactorial, only a small proportion of cases are thought to be associated with impaired in utero androgen exposure. The shorter AGD in boys with severe hypospadias compared with mild hypospadias would indicate that AGD is a marker of the severity of androgen production. This may also suggest that less severe forms of hypospadias have a different aetiology involving a later stage of development, and that they are not the result of reduced androgen exposure in the male programming window between the 8-14 weeks gestation. CONCLUSION: This study identified that boys with more severe hypospadias are more likely to have a shorter AGD and ASD than boys with mild hypospadias. This may indicate that there is a more profound impairment of in utero androgen action in severe hypospadias. PMID- 27670784 TI - Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation. AB - BACKGROUND: Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases. Yeast ALG1 (asparagine-linked glycosylation 1) encodes a beta-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol. ALG1 is essential for yeast viability, and in humans mutations in the ALG1 cause congenital disorders of glycosylation known as ALG1-CDG. Alg1 is difficult to purify because of its low expression level and as a consequence, has not been well studied biochemically. Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its beta-1, 4 mannosyltransferase activity. METHODS: N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography. In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity. In this assay, a chemically synthesized dolichol linked oligosaccharide analogue, phytanyl-pyrophosphoryl-alpha-N, N' diacetylchitobioside (PPGn2), was used as the acceptor for the beta-1, 4 mannosyl transfer reaction. RESULTS: Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor. Furthermore, the effect of ALG1-CDG mutations on enzyme activity was also measured. GENERAL SIGNIFICANCE: This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity. PMID- 27670785 TI - Infrared-emitting, peptidase-resistant fluorescent ligands of the bradykinin B2 receptor: application to cytofluorometry and imaging. AB - BACKGROUND: We have previously reported the design, pharmacological properties and imaging application of bradykinin (BK) B2 receptor (B2R) ligands conjugated with fluorophores such as fluorescein derivatives at their N-terminus. To take advantage of the high penetration of infrared light into living tissues and their low autofluorescence in this region of the spectrum, additional probes conjugated with cyanine dye 7 (Cy7) were synthesized and characterized. RESULTS: The antagonist B-9430 (D-Arg-[Hyp3,Igl5,D-Igl7,Oic8]-BK) and the agonist B-9972 (D Arg-[Hyp3,Igl5,Oic7,Igl8]-BK) were N-terminally extended with the infrared fluorophore Cy7, producing the peptides B-10665 and B-10666, respectively. Pharmacological studies indicated that the agonist B-10666 lost much affinity for the B2R vs. the parent peptide, whereas the antagonist B-10665 better retained its potency vs. B-9430 (competition of [3H]BK binding to human B2R, contractility of the human isolated umbilical vein for which potency losses were more important in each case). Both probes stained HEK 293 cells that expressed the B2R-green fluorescent protein (GFP) construction in a specific manner (confocal microscopy) and with very extensive co-localization of the green and infrared fluorescence in either case. The agonist B-10666 at 100 nM promoted the endocytosis of B2R-GFP in live cells, but not the antagonist version at 10-25 nM. The Cy7-labeled peptides did not label cells expressing the beta2-adrenoceptor-GFP construction. B-10665 at low nanomolar concentrations was an effective probe for the recombinant B2Rs in cytofluorometry and macroscopic imaging of cell wells (IVIS imaging system operated for infrared fluorescence detection). CONCLUSIONS: Despite a propensity for non-specific binding when used at high concentrations and limited sensitivity, Cy7-conjugated peptidase-resistant B2R ligands support original imaging and cytofluorometric applications. PMID- 27670787 TI - How salient are onomatopoeia in the early input? A prosodic analysis of infant directed speech. AB - Onomatopoeia are frequently identified amongst infants' earliest words (Menn & Vihman, 2011), yet few authors have considered why this might be, and even fewer have explored this phenomenon empirically. Here we analyze mothers' production of onomatopoeia in infant-directed speech (IDS) to provide an input-based perspective on these forms. Twelve mothers were recorded interacting with their 8 month-olds; onomatopoeic words (e.g. quack) were compared acoustically with their corresponding conventional words (duck). Onomatopoeia were more salient than conventional words across all features measured: mean pitch, pitch range, word duration, repetition, and pause length. Furthermore, a systematic pattern was observed in the production of onomatopoeia, suggesting a conventionalized approach to mothers' production of these words in IDS. PMID- 27670786 TI - N-acetylcysteine inhibits kinase phosphorylation during 3T3-L1 adipocyte differentiation. AB - OBJECTIVES: Reports investigating the effects of antioxidants on obesity have provided contradictory results. We have previously demonstrated that treatment with the antioxidant N-acetylcysteine (NAC) inhibits cellular triglyceride (Tg) accumulation as well as total cellular monoamine oxidase A (MAOA) expression in 3T3-L1 mature adipocytes (Calzadilla et al., Redox Rep. 2013;210-218). Here we analyzed the role of NAC on adipogenic differentiation pathway. METHODS: Assays were conducted using 3T3-L1 preadipocytes (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC). We studied the effects of different doses of NAC (0.01 or 1 mM) on DC, to evaluate cellular expression of phospho-JNK1/2 (pJNK1/2), phospho-ERK1/2 (pERK1/2) and, mitochondrial expression of citrate synthase, fumarate hydratase and MAOA. RESULTS: Following the differentiation of preadipocytes, an increase in the expression levels of pJNK1/2 and pERK1/2 was observed, together with mitotic clonal expansion (MCE). We found that both doses of NAC decreased the expression of pJNK1/2 and pERK1/2. Consistent with these results, NAC significantly inhibited MCE and modified the expression of different mitochondrial proteins. DISCUSSION: Our results suggested that NAC could inhibit Tg and mitochondrial protein expression by preventing both MCE and kinase phosphorylation. PMID- 27670789 TI - Postnatal morphological and lectin histochemical observation of the submucosal glands of rat nasopharynx. AB - The development of submucosal glands of rat nasopharynx was studied with respect to their morphological maturation and glycoprotein alterations during the postnatal period. This study examined the histological morphology with hematoxylin-eosin and the binding pattern of lectins, soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), Vicia villosa agglutinin (VVA), Ulex europaeus agglutinin-I (UEA-I), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and succinylated WGA (sucWGA) on frozen sections from newborn into adulthood. At birth, nasopharyngeal glands consisted of rudimentary secretory units which by postnatal day 3 (PN3) showed the characteristic features of salivary glands comprised of mixed mucous and serous cells. With maturation, serous cells increased in number and were arranged in clusters. Lectin reactivity at birth was detected at the acinar cell basal membranes for DBA, SBA, VVA, UEA-1 and PNA. At PN3, lectins labeled the apical cytoplasm and basolateral membranes of mucous cells and progressively with maturation, extended from the apical to basal portions of the cytoplasm with variable reactivity of VVA, PNA and sucWGA. Serous cells were labeled by UEA-1 starting from PN10 and also by PNA in adults. Ducts showed variable lectin reaction on the luminal membrane with strong reactivity of DBA and UEA-1 at PN21. Taken together, lectin histochemistry indicated the transitional occurrence of glycoproteins depending on the stage of maturation of the glands. Moreover, these results emphasize the difference in the morphology and lectin histochemistry between the nasopharyngeal and palatine glands. PMID- 27670788 TI - Acute kidney injury 2016: diagnosis and diagnostic workup. AB - Acute kidney injury (AKI) is common and is associated with serious short- and long-term complications. Early diagnosis and identification of the underlying aetiology are essential to guide management. In this review, we outline the current definition of AKI and the potential pitfalls, and summarise the existing and future tools to investigate AKI in critically ill patients. PMID- 27670790 TI - CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. AB - The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity. PMID- 27670792 TI - Prognostic Usefulness of the Ballooning Pattern in Patients With Takotsubo Cardiomyopathy. AB - The aim of the present analysis was to evaluate the prognostic impact of different ballooning patterns in patients with Takotsubo cardiomyopathy (TTC). A total of 285 consecutive patients with TTC were included. Clinical characteristics and short- and long-term outcomes were compared between patients with typical apical ballooning (n = 204) and patients with an atypical ballooning pattern including midventricular and basal ballooning (n = 81). Patients with typical apical ballooning were significantly older (73.3 +/- 10.2 vs 68.4 +/- 10.3 years; p <0.01) and had a higher prevalence of diabetes mellitus (25.5% vs 12.3%; p = 0.02). The initial left ventricular (LV) ejection fraction was significantly lower in case of apical ballooning (41.5 +/- 10.4% vs 46.9 +/- 10.9%; p <0.01) but recovered to normal values in both groups (58.4 +/- 8.0 vs 59.7 +/- 7.0; p = 0.25). Although 28-day mortality did not differ significantly (p = 0.10), typical apical ballooning was associated with an increased 6-month (13.4% vs 1.3%; hazard ratio [HR] 10.81, 95% confidence interval [CI] 1.47 to 79.66; p = 0.02) and long-term mortality rates (28.9% vs 14.5%; HR 2.24, 95% CI 1.17 to 4.71; p = 0.02). A landmark analysis which included only patients who survived the first 6 months after the initial event demonstrated similar mortality rates in patients with typical (17.9%) and atypical (13.3%) ballooning (HR 1.36, 95% CI 0.67 to 2.79; p = 0.40). In conclusion, in patients with TTC, typical apical ballooning is associated with more severe LV dysfunction at acute presentation and higher mortality rates within the first 6 months after the initial event. After complete recovery of LV function, prognosis is similar in patients with typical and atypical ballooning patterns. PMID- 27670794 TI - Usefulness of the CHADS2 Score for Determining Risk of Seizure in Patients With Atrial Fibrillation. AB - Atrial fibrillation (AF) secondary to seizure has been described in case reports, but the association between AF and risk of seizure has never been evaluated in longitudinal studies. The objectives of this study were to investigate the role of AF on the risk of development of seizure and the usefulness of CHADS2 score for predicting the risk of seizure. Our analyses were conducted using information from a random sample of 1 million subjects enrolled in Taiwan National Health Insurance Research Database. A total of 11,552 subjects aged >=18 years, comprising 5,776 subjects diagnosed with AF during the study period and 5,776 age and sex-matched subjects without AF were enrolled in our study. During the mean follow-up of 6.7 +/- 3.3 years, seizure events occurred in 235 patients. In comparison, the AF group had a higher incidence rate of seizure occurrence (4.17 vs 1.90 per 1,000 person-years). Cox proportional hazard regression model analysis showed that development of AF was independently associated with a higher risk of developing future seizure (adjusted HR 2.30; 95% confidence interval 1.73 to 3.05). In multivariate Cox regression analysis adjusted for potentially confounding variables, a higher CHADS2 score was associated with a higher risk of seizure in a dose-dependent manner. AF may cause an ischemic stroke that subsequently leads to seizure, and present study further demonstrates that AF patients are associated with higher rate of subsequent seizure, even after adjusting for stroke. The CHADS2 score was found to be a useful scheme for predicting the risk of seizure occurrence. PMID- 27670791 TI - The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis. AB - The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro-inflammatory repertoire of lung monocytes and monocyte-derived dendritic cells recruited during acute inflammation. Here, we review the identity and functions of all lung macrophage and monocyte subsets during homoeostasis and acute lung inflammation, with a special focus on their contributions to influenza virus detection, clearance and the development of influenza-induced lung pathologies. Subsequent implications for the development of new therapeutic targets against influenza-induced lung pathologies will also be discussed. PMID- 27670793 TI - Relation of Statin Use and Mortality in Community-Dwelling Frail Older Patients With Coronary Artery Disease. AB - Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged >=65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA 1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1, -2, and -3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and >=85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins. PMID- 27670796 TI - Catheter Closure Through a Venous Approach of Patent Ductus Arteriosus in Small Pediatric Patients Using Combined Angiographic and Echocardiographic Guidance. AB - The standard technique of catheter closure of patent ductus arteriosus (PDA) may be associated with arterial complications particularly in small pediatric patients. The aim of this study was to evaluate whether catheter closure of PDA in small children using an exclusive venous approach is a safe and effective alternative to closure with the standard technique. One hundred-twelve patients, aged 2 to 24 months, were randomly assigned in a 1:1 ratio to catheter closure of PDA using the standard technique (group 1) and an exclusive venous approach (group 2), respectively. In group 2, the procedure was guided using hand injections of contrast media through the delivery sheath and 2-dimensional and color Doppler echocardiography. Group 1: the PDA diameter ranged from 2 to 5.5 mm and the device diameter ranged from 4 to 8 mm. The PDA occluders were permanently implanted in all patients. Five losses of the arterial pulses that were restored with intravenous infusion of heparin and recombinant tissue plasminogen activator (rtPA), and 4 groin hematomas were the main complications of the procedure. Group 2: the mean PDA diameter ranged from 2.5 to 6 mm and the device diameter ranged from 3 to 8 mm. The PDA occluders were permanently implanted in all but 2 patients. There were no complications. Complete echocardiographic closure of PDA at 1-month follow-up was observed in all 110 patients. Exclusive transvenous PDA occlusion is an effective and safe technique that prevents the arterial complications of the standard approach in small children. PMID- 27670795 TI - Magnetic Resonance Venous Volume Measurements in Peripheral Artery Disease (from ELIMIT). AB - The relation between the arterial and venous systems in patients with impaired lower extremity blood flow remains poorly described. The objective of this secondary analysis of the Effectiveness of Intensive Lipid Modification Medication in Preventing the Progression on Peripheral Artery Disease Trial was to determine the association between femoral vein (FV) volumes and measurements of peripheral artery disease. FV wall, lumen, and total volumes were quantified with fast spin-echo proton density-weighted magnetic resonance imaging scans in 79 patients with peripheral artery disease over 2 years. Reproducibility was excellent for FV total vessel (intraclass correlation coefficient 0.924, confidence interval 0.910 to 0.935) and lumen volumes (intraclass correlation coefficient 0.893, confidence interval 0.873 to 0.910). Baseline superficial femoral artery volumes were directly associated with FV wall (r = 0.46, p <0.0001), lumen (r = 0.42, p = 0.0001), and total volumes (r = 0.46, p <0.0001). The 2-year change in maximum walking time was inversely associated with the 24 month change in FV total volume (r = -0.45, p = 0.03). In conclusion, FV volumes can be measured reliably with fast spin-echo proton density-weighted magnetic resonance imaging, and baseline superficial femoral artery plaque burden is positively associated with FV volumes, whereas the 2-year change in FV volumes and leg function show an inverse relation. PMID- 27670797 TI - Effect of Beta-Blocker Therapy, Maximal Heart Rate, and Exercise Capacity During Stress Testing on Long-Term Survival (from The Henry Ford Exercise Testing Project). AB - Whether lower heart rate thresholds (defined as the percentage of age-predicted maximal heart rate achieved, or ppMHR) should be used to determine chronotropic incompetence in patients on beta-blocker therapy (BBT) remains unclear. In this retrospective cohort study, we analyzed 64,549 adults without congestive heart failure or atrial fibrillation (54 +/- 13 years old, 46% women, 29% black) who underwent clinician-referred exercise stress testing at a single health care system in Detroit, Michigan from 1991 to 2009, with median follow-up of 10.6 years for all-cause mortality (interquartile range 7.7 to 14.7 years). Using Cox regression models, we assessed the effect of BBT, ppMHR, and estimated exercise capacity on mortality, with adjustment for demographic data, medical history, pertinent medications, and propensity to be on BBT. There were 9,259 deaths during follow-up. BBT was associated with an 8% lower adjusted achieved ppMHR (91% in no BBT vs 83% in BBT). ppMHR was inversely associated with all-cause mortality but with significant attenuation by BBT (per 10% ppMHR HR: no BBT: 0.80 [0.78 to 0.82] vs BBT: 0.89 [0.87 to 0.92]). Patients on BBT who achieved 65% ppMHR had a similar adjusted mortality rate as those not on BBT who achieved 85% ppMHR (p >0.05). Estimated exercise capacity further attenuated the prognostic value of ppMHR (per-10%-ppMHR HR: no BBT: 0.88 [0.86 to 0.90] vs BBT: 0.95 [0.93 to 0.98]). In conclusion, the prognostic value of ppMHR was significantly attenuated by BBT. For patients on BBT, a lower threshold of 65% ppMHR may be considered for determining worsened prognosis. Estimated exercise capacity further diminished the prognostic value of ppMHR particularly in patients on BBT. PMID- 27670798 TI - Emendation of Propionibacterium acnes subsp. acnes (Deiko et al. 2015) and proposal of Propionibacterium acnes type II as Propionibacterium acnes subsp. defendens subsp. nov. AB - Recently, it has been proposed that strains of Propionibacterium acnes from the type III genetic division should be classified as P. acnessubsp. elongatum subsp. nov., with strains from the type I and II divisions collectively classified as P. acnessubsp. acnes subsp. nov. Under such a taxonomic re-appraisal, we believe that types I and II should also have their own separate rank of subspecies. In support of this, we describe a polyphasic taxonomic study based on the analysis of publicly available multilocus and whole-genome sequence datasets, alongside a systematic review of previously published phylogenetic, genomic, phenotypic and clinical data. Strains of types I and II form highly distinct clades on the basis of multilocus sequence analysis (MLSA) and whole-genome phylogenetic reconstructions. In silico or digital DNA-DNA similarity values also fall within the 70-80 % boundary recommended for bacterial subspecies. Furthermore, we see important differences in genome content, including the presence of an active CRISPR/Cas system in type II strains, but not type I, and evidence for increasing linkage equilibrium within the separate divisions. Key biochemical differences include positive test results for beta-haemolytic, neuraminidase and sorbitol fermentation activities with type I strains, but not type II. We now propose that type I strains should be classified as P. acnessubsp. acnes subsp. nov., and type II as P. acnessubsp. defendens subsp. nov. The type strain of P. acnessubsp. acnes subsp. nov. is NCTC 737T (=ATCC 6919T=JCM 6425T=DSM 1897T=CCUG 1794T), while the type strain of P. acnessubsp. defendens subsp. nov. is ATCC 11828 (=JCM 6473=CCUG 6369). PMID- 27670800 TI - Assembly of Heterometallic Silver(I)-Copper(I) Alkyl-1,3-diynyl Clusters via Inner-Core Expansion. AB - New tetranuclear supramolecular precursors [(R-C=C-C=C)Ag]4 (R = iPr, tBu, and chx) are employed to construct a series of heterometallic silver(I)-copper(I) alkyl-1,3-diynyl cluster complexes (1-9) that bear a common CuAg3 core (normally trigonal-planar, but can be distorted to pyramidal) consolidated by cupro argentophilic interaction under 3.12 A, as found in 1 and 2. The photophysical properties of the multinuclear supramolecular precursors and selected complexes have been investigated. The present results strongly suggest that the assembly of medium-nuclearity clusters 3 to 9 is initiated by accretion of additional Ag(I) ions by the ubiquitous CuAg3 template through argentophilic (<3.4 A) interaction, with cooperative cuprophilic enhancement (<2.76 A) in the case of compound 9. To our knowledge, the present study provides the first report of conversion of a Group 11 homonuclear cluster into a heteronuclear one of higher nuclearity via inner-core expansion. PMID- 27670799 TI - A population-wide applicable HLA-DQ2 and DQ8 genotyping using DNA from dried blood spots and duplex allele-specific qPCR amplification. AB - Genotyping of HLA-DQ2 and DQ8 haplotypes is important for diagnosis or for screening of early risk detection of celiac disease or type 1 diabetes. Usually, venous blood DNA extraction and expensive and time consuming amplification are used, that hinder population-wide studies. We assayed a friendly HLA-DQ2 and DQ8 genotyping procedure using a combination of DNA from dried blood spot (DBS) and duplex allele-specific qPCR amplification using SYBR Green. DNA was extracted using home-made buffers and compared to an extraction commercial kit. Duplex reactions by qPCR were designed using each Tm allele amplicon for reference samples (positive HLA-DQ2 or DQ8) with allele-specific primers. DBS samples from 558 children (7.99 +/- 2.47 y) were collected. The DNA final yield obtained by the home-made extractive procedure was higher than from the commercial kit (1.11 +/- 0.56 vs 0.23 +/- 0.14 MUg), while the quality was similar for both DNA samples. There was concordance in the amplification profiles for DNA samples obtained with both methods. All of four alleles from DQ2 and DQ8 haplotypes were accurately identified in duplex reactions. By using DBS samples and DNA extraction home-made procedure, the costs were reduced by 60%. The whole procedure is cost-effective for HLA-DQ2 and DQ8 genotyping. PMID- 27670801 TI - Clinical Practice Audit of Perioperative Antimicrobial Prophylaxis in a Tertiary Care Hospital: Do Routine Academic Activities Improve Adherence to Practice Guidelines? AB - BACKGROUND: Antimicrobial prophylaxis should be used in circumstances where efficacy has been demonstrated and benefits outweigh the risk. Each hospital must have an antibiotic policy that is implementable and fully adhered to. METHODS: A prospective observational study was conducted in 209 patients, admitted to wards of various surgical departments including surgery, obstetrics & gynaecology (O&G), otorhinolaryngology (ENT) and orthopaedics. Relevant antimicrobial use data of each patient was collected in a customized Case Record Form (CRF) from day one until patient was discharged. RESULTS: Majority of the patients were young adults between 19-39 years of age. Preoperative antibiotics were given in 151 and postoperative antibiotics were prescribed in all. Third generation cephalosporins was the most frequently prescribed group. The selection of antibiotics by different departments varied greatly and many prescribed (n=85) two antibiotics for preoperative prophylaxis. Average duration of surgical prophylaxis was 6.25 days. In 90 patients, preoperative antibiotic was administered before 3 hours. CONCLUSION: Despite routine interactive academic activities, pattern of antibiotic used was not as per guidelines suggested by competent authorities. Interventions are warranted to promote the development, dissemination and adoption of evidence based antibiotic policy. The policy should be simple, clear, noncontroversial, clinically relevant and implementable. The constant monitoring with periodic audit to ensure adherence is warranted. PMID- 27670802 TI - MMP-TIMP interactions in cancer invasion: An evolutionary game-theoretical framework. AB - One of the main steps in solid cancers to invade surrounding tissues is degradation of tissue barriers in the extracellular matrix. This operation that leads to initiate, angiogenesis and metastasis to other organs, is essentially consequence of collapsing dynamic balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). In this work, we model the MMP-TIMP interaction in both normal tissue and invasive cancer using evolutionary game theory. Our model explains how invasive cancer cells get the upper hand in MMP-TIMP imbalance scenarios. We investigate dynamics of them over time and discuss stable and nonstable states in the population. Numerical simulations presented here provide the identification of key genotypic features in the tumor invasion and a natural description for phenotypic variability. The simulation results are consistent with the experimental results in vitro observations presented in medical literature. Finally, by the provided results the necessary conditions to inhibit cancer invasion or prolong its course are explained. In this way, two therapeutic approaches with respect to how they could meet the required conditions are considered. PMID- 27670803 TI - Combination with anti-tit-for-tat remedies problems of tit-for-tat. AB - One of the most important questions in game theory concerns how mutual cooperation can be achieved and maintained in a social dilemma. In Axelrod's tournaments of the iterated prisoner's dilemma, Tit-for-Tat (TFT) demonstrated the role of reciprocity in the emergence of cooperation. However, the stability of TFT does not hold in the presence of implementation error, and a TFT population is prone to neutral drift to unconditional cooperation, which eventually invites defectors. We argue that a combination of TFT and anti-TFT (ATFT) overcomes these difficulties in a noisy environment, provided that ATFT is defined as choosing the opposite to the opponent's last move. According to this TFT-ATFT strategy, a player normally uses TFT; turns to ATFT upon recognizing his or her own error; returns to TFT either when mutual cooperation is recovered or when the opponent unilaterally defects twice in a row. The proposed strategy provides simple and deterministic behavioral rules for correcting implementation error in a way that cannot be exploited by the opponent, and suppresses the neutral drift to unconditional cooperation. PMID- 27670804 TI - Medical and psychological factors related to pain in adults with pediatric-onset spinal cord injury: a biopsychosocial model. AB - STUDY DESIGN: A cross-sectional study. OBJECTIVES: The aim of this study is to determine medical and psychological correlates of pain in individuals with pediatric-onset spinal cord injury (SCI). SETTING: Shriners Hospitals for Children-Chicago, Philadelphia and Northern California (USA). METHODS: A total of 187 adults who had sustained an injury before 19 years of age completed interviews that included medical information, standardized measures of psychological functioning (Beck Anxiety Inventory and Patient Health Questionnaire) and a comprehensive pain questionnaire to assess the location, frequency, intensity and duration of pain and distress and disability related to pain. RESULTS: The findings identified the medical and psychological correlates of pain. Greater symptoms of depression and anxiety were strong and consistent predictors of several aspects of pain, above and beyond the impact of gender, injury-related characteristics and secondary medical complications. DISCUSSION: The findings support a biopsychosocial model of the development and persistence of pain in individuals with pediatric-onset SCI. Interdisciplinary rehabilitation may incorporate psychological treatment such as cognitive-behavioral therapy to reduce the pain and improve functioning. The assessment and treatment of pain in pediatric-onset SCI is a clinical and research priority. SPONSORSHIP: This study is supported by funding from Shriners Hospitals for Children and the Craig H. Neilsen Foundation, grant #324671. PMID- 27670805 TI - Identification of patients with cervical SCI suitable for early nerve transfer to achieve hand opening. AB - STUDY DESIGN: Retrospective audit. OBJECTIVES: The objective of this study was to identify the proportion of patients with cervical spinal cord injury who would potentially benefit from nerve transfer surgery to gain active hand opening, and to determine when a safe nerve transfer decision can be made. SETTING: Christchurch, New Zealand. METHODS: Case note review of the first 12 months following acute cervical spinal cord injury (2007-2012). Neurological assessment at 6 weeks, 12 weeks and 1 year following injury. RESULTS: Fifty-three patients had complete assessments and showed changes in the level of injury and severity of neurological injury between assessments. Forty-two percent of patients had motor complete C5-7 level injuries 12 weeks following injury and would benefit from consideration for nerve transfer to improve hand opening. Fewer (26%) would benefit 1 year following injury owing to a change in the neurological level of injury. CONCLUSIONS: Twelve-week neurological assessment identifies patients who may benefit from nerve transfer surgery. This enables referral for comprehensive upper limb assessment and reassessment of motor function to determine suitability for surgical intervention. Nerve transfer within the window of opportunity provides active hand opening for patients following cervical spinal cord injury. PMID- 27670806 TI - Retrospective assessment of the validity and use of the community balance and mobility scale among individuals with subacute spinal cord injury. AB - STUDY DESIGN: This is a retrospective chart review. OBJECTIVES: The objective of this study was to evaluate the convergent validity, internal consistency and use of the Community Balance & Mobility Scale (CB&M) in individuals with incomplete spinal cord injury (iSCI) during inpatient rehabilitation. SETTING: This study was conducted in an SCI rehabilitation center in Canada. METHODS: Inpatient charts from January 2009 to October 2015 were screened. A chart was excluded if the inpatient was aged >65 years, did not complete a CB&M and/or had a comorbid condition. Demographics, CB&M score and injury-related characteristics were extracted. Berg Balance Scale (BBS), Six-Minute Walk Test (6 MWT) and Ten-Meter Walk Test (10 mWT) scores were obtained if completed within 1 week of the CB&M. chi2-Tests were used to identify CB&M items that were uniformly distributed, implying good discrimination between individuals. Convergent validity was assessed by correlating (Pearson's r) CB&M scores with BBS, 6 MWT and 10 mWT scores. Internal consistency (Cronbach's alpha) was evaluated. RESULTS: Thirty inpatients were included (23 male, 38.3+/-15.3 years old, three AIS C, 26 AIS D, C1-L4, 16 traumatic). BBS scores were ?51/56; however, CB&M scores showed a wider range (27-82/96). Unilateral Stance, Tandem Walking, Lateral Foot Scooting, Forward to Backward Walking and Descending Stairs showed uniform distributions. Scores on the CB&M correlated strongly with scores on the 6 MWT (r=0.72, P<0.001) and moderately strongly with 10 mWT and BBS scores (r=0.47-0.59, P=0.004-0.013). Cronbach's alpha=0.87. CONCLUSIONS: The CB&M is a valid measure in high functioning individuals with iSCI. Prospective studies are required to further evaluate the psychometric properties of the CB&M as a measure of high-level balance for SCI. PMID- 27670807 TI - Self-harm and suicide before and after spinal cord injury: a systematic review. AB - STUDY DESIGN: This is a systematic literature review. OBJECTIVES: The objectives of this study were to investigate, first, the proportion of spinal cord injury (SCI) caused by suicidal behaviour; second, the proportion of deaths in the SCI population caused by suicide; and third, the risk factors associated with suicidal behaviour. SETTING: This study was conducted in the UK. METHODS: AMED, EMBASE, HMIC, BNI, Medline, PsycInfo, CINAHL and HEALTH BUSINESS ELITE were searched between January and February 2016, identifying a total of 404 articles published between 1990 and 2016. Full articles, written in English, looking at suicide before and after SCI were selected. On the basis of the inclusion criteria, 22 relevant articles were included in this literature review. RESULTS: Studies reported that between 0 and 6.8% of individuals with SCI had acquired their injury as a result of attempted suicide. The predominant method used in these attempts was deliberate falling/jumping from buildings and bridges. Suicidal behaviour post SCI was frequently reported as a cause of death; studies reported that between 5.8 and 11% of deaths were a result of suicide. The predominant methods used were gunshot and overdose. Psychiatric diagnoses were identified to be a major risk factor for suicidal behaviour. CONCLUSION: Individuals with SCI are at risk of attempting suicide; this risk is increased by the presence of a psychiatric diagnosis. There is a crucial need for risk assessment and psychological intervention for individuals with mental health issues following SCI. PMID- 27670808 TI - Pregnancy in spinal cord-injured women, a cohort study of 37 pregnancies in 25 women. AB - STUDY DESIGN: A retrospective observational study. OBJECTIVE: To describe specificities of pregnancy in a traumatic spinal cord-injured (SCI) population managed by a coordinated medical care team involving physical medicine and rehabilitation (PMR) physicians, urologists, infectious diseases' physicians, obstetricians and anaesthesiologists. SETTING: NeuroUrology Department in a University Hospital, France. METHODS: All consecutive SCI pregnant women managed between 2001 and 2014 were included. A preconceptional consultation was proposed whenever possible. Obstetrical and urological outcomes, delivery mode and complications were reported. RESULTS: Overall, thirty-seven pregnancies in 25 women, of a mean age of 32+/-4 years, were included. Thirty-five children were born alive (three miscarriages, a twin pregnancy) without complications except for a case of neonatal respiratory distress in premature twins born at 33 weeks. The mean birth weight was 2979+/-599 g. Twenty-one (57%) pregnancies benefited from preconceptional care. A weekly oral cyclic antibiotic programme was prescribed in 28 (75%) pregnancies. The main complications during pregnancy included pyelonephritis (30%), lower urinary tract infections (UTI) (32%), pressure sores (8.8%) and prematurity (12% deliveries before 37 weeks, with only one delivery before 36 weeks). Two patients suffered from autonomic dysreflexia, one with serious complication (brain haematoma). Caesarean sections were performed for 68% of deliveries (23/34) to prevent syringomyelia deterioration (n=10), stress urinary incontinence aggravation (n=3) or for obstetrical reasons (n=7). CONCLUSIONS: Mothers' and infants' outcomes were satisfying after pregnancy in SCI women, but required many adjustments. Pregnancy must be prepared by a preconceptional consultation, and managed by a multidisciplinary team involving specialists of neurological disability and pregnancy. PMID- 27670810 TI - Response to 'On Complicity and Compromise' by Chiara Lepora and Robert Goodin. PMID- 27670809 TI - The Colletotrichum gloeosporioides RhoB regulates cAMP and stress response pathways and is required for pathogenesis. AB - Rho GTPases regulate morphology and multiple cellular functions such as asexual development, polarity establishment, and differentiation in fungi. To determine the roles of CgRhoB, a Rho GTPase protein, here we characterized CgRhoB in the poplar anthracnose fungus Colletotrichum gloeosporioides. First of all, we determined that conidial germination was inhibited and intracellular cyclic AMP (cAMP) level was increased in the CgRhoB deletion mutants. Loss of CgRhoB resulted in shorter germ tubes and enhanced appressoria formation after germination on the hydrophobic surface. Exogenous addition of cAMP to the wild type generated the similar phenotypes of DeltaCgRhoB inoculated in CM liquid. Furthermore, deletion of CgRhoB had discernible effect upon the sensitivity of C. gloeosporioides to cell wall perturbing agents and altered the distribution of chitin on the cell wall. H2O2 sensitivity assay showed the hypersensitive effect on the oxidative stress, and transcriptional analysis revealed that transcription of genes involved in peroxidase activities was altered in the mutants. Finally, virulence assay revealed that CgRhoB was required for pathogenicity. Taken together, our results showed that CgRhoB was associated with appressoria formation and pathogenicity, and affected cAMP level and stress pathways. PMID- 27670811 TI - Risk and radical uncertainty in HIV research. AB - How much risk can we expose our research subjects to? There is a special challenge answering this question when the evidence on which we base our assessments of risk is fragmentary, conflicting or sparse. Such evidence does not support precise assignments of risk (eg, there is a 24.8% chance that this patient will develop AIDS in the next year if she participates in my study). At best it supports imprecise assignments of risk (eg, there is between a 5% and 35% chance that this patient will develop AIDS in the next year if she participates in my study). Here I discuss three approaches to evaluating risk when probability assignments are imprecise-an optimistic approach, a moderate approach and a pessimistic approach. I offer a practical reason to favour the pessimistic approach. PMID- 27670812 TI - Erratum to Cytomegalovirus pUL50 is the multi-interacting determinant of the core nuclear egress complex (NEC) that recruits cellular accessory NEC components. PMID- 27670814 TI - Signaling by sulfur-containing molecules. Quantitative aspects. AB - There is currently interest in sulfur-containing molecules that may or may not play a role in signaling. We have collected relevant thermodynamic data, namely standard Gibbs energies of formation and electrode potentials at pH 7, and used these to construct a Frost diagram. Thermodynamic data not available in the literature could be estimated with reasonable confidence. At pH 7, the electrode potential of the RSS/RSS- couple is +0.68 V, 0.28 V less than that of the RS, H+/RSH couple. S2- is unstable with respect to HSS- and S2. Generally, polysulfur compounds, with the exception of RSSR, are thermodynamically unstable with respect to disproportionation and ultimately lead to formation of kinetically inert S8(s). About thermoneutral is the formation of RSS- from RSSR and HS-, but formation of HNO from HS- and SNO-, and from HS- and RSNO, is unfavorable. The formation of SSNO-in vivo is kinetically unlikely. PMID- 27670813 TI - A multifaceted intervention to reduce drug-related complications in surgical patients. AB - AIM: The P-REVIEW study was a prospective, multicenter, open intervention study, designed to determine whether a multifaceted intervention of educating the prescriber combined with medication review and pharmaceutical visits to the ward by the hospital pharmacist could lead to a reduction in drug-related complications among surgical patients. METHODS: A total of 6780 admissions of 5940 patients to surgical, urological and orthopaedic wards during the usual care period and 6484 admissions of 5711 patients during the intervention period were included. An educational programme covering pain management, antithrombotics, fluid and electrolyte management, prescription in case of renal insufficiency and antibiotics was developed. National and local hospital guidelines were included. Hospital pharmacists performed medication safety consultations, combining medication review of high-risk patients and a visit to the physician on the ward. RESULTS: A significantly lower proportion of admissions with one or more clinically relevant, potentially preventable, drug-related problems (including death, temporary or sustained disability, increased length of hospital stay or readmission within 30 days) occurred in the intervention period (1.1% (73/6484) compared to the usual care period [1.6% (106/6780)] (P = 0.029). The relative risk (RR) was 0.72 (95% CI 0.53-0.97). Several types of drug-related problems occurred less frequently. Costs incurred as result of time spent on study-related activities were not different before and after the intervention. CONCLUSIONS: The P-REVIEW study shows that education and support of the prescribing physician with respect to high-risk patients in surgical departments leads to a significant, clinically relevant benefit for patients without generating additional costs. PMID- 27670815 TI - Behavioural fever in zebrafish larvae. AB - Behavioural fever has been reported in different species of mobile ectotherms including the zebrafish, Danio rerio, in response to exogenous pyrogens. In this study we report, to our knowledge for the first time, upon the ontogenic onset of behavioural fever in zebrafish (Danio rerio) larvae. For this, zebrafish larvae (from first feeding to juveniles) were placed in a continuous thermal gradient providing the opportunity to select their preferred temperature. The novel thermal preference aquarium was based upon a continuous vertical column system and allows for non-invasive observation of larvae vertical distribution under isothermal (TR at 28 degrees C) and thermal gradient conditions (TCH: 28-32 degrees C). Larval thermal preference was assessed under both conditions with or without an immersion challenge, in order to detect the onset of the behavioural fever response. Our results defined the onset of the dsRNA induced behavioural fever at 18-20 days post fertilization (dpf). Significant differences were observed in dsRNA challenged larvae, which prefer higher temperatures (1-4 degrees C increase) throughout the experimental period as compared to non challenged larvae. In parallel we measured the abundance of antiviral transcripts; viperin, gig2, irf7, trim25 and Mxb mRNAs in dsRNA challenged larvae under both thermal regimes: TR and TCh. Significant increases in the abundance of all measured transcripts were recorded under thermal choice conditions signifying that thermo-coupling and the resultant enhancement of the immune response to dsRNA challenge occurs from 18 dpf onwards in the zebrafish. The results are of importance as they identify a key developmental stage where the neuro-immune interface matures in the zebrafish likely providing increased resistance to viral infection. PMID- 27670816 TI - Evolutionary and Functional Analysis of Membrane-Bound NAC Transcription Factor Genes in Soybean. AB - Functional divergence is thought to be an important evolutionary driving force for the retention of duplicate genes. We reconstructed the evolutionary history of soybean (Glycine max) membrane-bound NAC transcription factor (NTL) genes. NTLs are thought to be components of stress signaling and unique in their requirement for proteolytic cleavage to free them from the membrane. Most of the 15 GmNTL genes appear to have evolved under strong purifying selection. By analyzing the phylogenetic tree and gene synteny, we identified seven duplicate gene pairs generated by the latest whole-genome duplication. The members of each pair were shown to have variously diverged at the transcriptional (organ specificity and responsiveness to stress), posttranscriptional (alternative splicing), and protein (proteolysis-mediated membrane release and transactivation activity) levels. The dormant (full-length protein) and active (protein without a transmembrane motif) forms of one pair of duplicated gene products (GmNTL1/GmNLT11) were each separately constitutively expressed in Arabidopsis (Arabidopsis thaliana). The heteroexpression of active but not dormant forms of these proteins caused improved tolerance to abiotic stresses, suggesting that membrane release was required for their functionality. Arabidopsis carrying the dormant form of GmNTL1 was more tolerant to hydrogen peroxide, which induces its membrane release. Tolerance was not increased in the line carrying dormant GmNTL11, which was not released by hydrogen peroxide treatment. Thus, NTL-release pattern changes may cause phenotypic divergence. It was concluded that a variety of functional divergences contributed to the retention of these GmNTL duplicates. PMID- 27670820 TI - Man vs. manikin revisited - the ethical boundaries of simulating difficult airways in patients. PMID- 27670818 TI - Disclosing the Molecular Basis of the Postharvest Life of Berry in Different Grapevine Genotypes. AB - The molecular events that characterize postripening grapevine berries have rarely been investigated and are poorly defined. In particular, a detailed definition of changes occurring during the postharvest dehydration, a process undertaken to make some particularly special wine styles, would be of great interest for both winemakers and plant biologists. We report an exhaustive survey of transcriptomic and metabolomic responses in berries representing six grapevine genotypes subjected to postharvest dehydration under identical controlled conditions. The modulation of phenylpropanoid metabolism clearly distinguished the behavior of genotypes, with stilbene accumulation as the major metabolic event, although the transient accumulation/depletion of anthocyanins and flavonols was the prevalent variation in genotypes that do not accumulate stilbenes. The modulation of genes related to phenylpropanoid/stilbene metabolism highlighted the distinct metabolomic plasticity of genotypes, allowing for the identification of candidate structural and regulatory genes. In addition to genotype-specific responses, a core set of genes was consistently modulated in all genotypes, representing the common features of berries undergoing dehydration and/or commencing senescence. This included genes controlling ethylene and auxin metabolism as well as genes involved in oxidative and osmotic stress, defense responses, anaerobic respiration, and cell wall and carbohydrate metabolism. Several transcription factors were identified that may control these shared processes in the postharvest berry. Changes representing both common and genotype-specific responses to postharvest conditions shed light on the cellular processes taking place in harvested berries stored under dehydrating conditions for several months. PMID- 27670817 TI - The Genetics of Leaf Flecking in Maize and Its Relationship to Plant Defense and Disease Resistance. AB - Physiological leaf spotting, or flecking, is a mild-lesion phenotype observed on the leaves of several commonly used maize (Zea mays) inbred lines and has been anecdotally linked to enhanced broad-spectrum disease resistance. Flecking was assessed in the maize nested association mapping (NAM) population, comprising 4,998 recombinant inbred lines from 25 biparental families, and in an association population, comprising 279 diverse maize inbreds. Joint family linkage analysis was conducted with 7,386 markers in the NAM population. Genome-wide association tests were performed with 26.5 million single-nucleotide polymorphisms (SNPs) in the NAM population and with 246,497 SNPs in the association population, resulting in the identification of 18 and three loci associated with variation in flecking, respectively. Many of the candidate genes colocalizing with associated SNPs are similar to genes that function in plant defense response via cell wall modification, salicylic acid- and jasmonic acid-dependent pathways, redox homeostasis, stress response, and vesicle trafficking/remodeling. Significant positive correlations were found between increased flecking, stronger defense response, increased disease resistance, and increased pest resistance. A nonlinear relationship with total kernel weight also was observed whereby lines with relatively high levels of flecking had, on average, lower total kernel weight. We present evidence suggesting that mild flecking could be used as a selection criterion for breeding programs trying to incorporate broad-spectrum disease resistance. PMID- 27670821 TI - Thermal conductivity of amorphous Al2O3/TiO2 nanolaminates deposited by atomic layer deposition. AB - The thermophysical properties of Al2O3/TiO2 nanolaminates deposited by atomic layer deposition (ALD) are studied as a function of bilayer thickness and relative TiO2 content (0%-100%) while the total nominal thickness of the nanolaminates was kept at 100 nm. Cross-plane thermal conductivity of the nanolaminates is measured at room temperature using the nanosecond transient thermoreflectance method. Based on the measurements, the nanolaminates have reduced thermal conductivity as compared to the pure amorphous thin films, suggesting that interfaces have a non-negligible effect on thermal transport in amorphous nanolaminates. For a fixed number of interfaces, we find that approximately equal material content of Al2O3 and TiO2 produces the lowest value of thermal conductivity. The thermal conductivity reduces with increasing interface density up to 0.4 nm(-1), above which the thermal conductivity is found to be constant. The value of thermal interface resistance approximated by the use of diffuse mismatch model was found to be 0.45 m(2) K GW(-1), and a comparative study employing this value supports the interpretation of non-negligible interface resistance affecting the overall thermal conductivity also in the amorphous limit. Finally, no clear trend in thermal conductivity values was found for nanolaminates grown at different deposition temperatures, suggesting that the temperature in the ALD process has a non-trivial while modest effect on the overall thermal conductivity in amorphous nanolaminates. PMID- 27670822 TI - The art of presenting - Failures, fonts and the future. AB - Many of you, like me, will have given countless presentations throughout your career and to wide and varied audiences. I too, like many of you, have never been formally taught how to present, if that is such a thing. So, I got to thinking: in any case, who are "expert presenter" teachers? Some people have it and some people do not - right? In this short piece, I explore what it is to present, how this evolves, and try to pin down the why rather than the how and give you a little insight into my haphazard journey along this process. PMID- 27670819 TI - Phloem Transport of the Receptor DWARF14 Protein Is Required for Full Function of Strigolactones. AB - The cell-to-cell transport of signaling molecules is essential for multicellular organisms to coordinate the action of their cells. Recent studies identified DWARF14 (D14) as a receptor of strigolactones (SLs), molecules that act as plant hormones and inhibit shoot branching. Here, we demonstrate that RAMOSUS3, a pea ortholog of D14, works as a graft-transmissible signal to suppress shoot branching. In addition, we show that D14 protein is contained in phloem sap and transported through the phloem to axillary buds in rice. SLs are not required for the transport of D14 protein. Disruption of D14 transport weakens the suppression of axillary bud outgrowth of rice. Taken together, we conclude that the D14 protein works as an intercellular signaling molecule to fine-tune SL function. Our findings provide evidence that the intercellular transport of a receptor can regulate the action of plant hormones. PMID- 27670824 TI - [Immunology and immunosuppression in kidney transplantation. ABO and HLA incompatible kidney transplantation]. AB - OBJECTIVES: To perform a state of the art about immunological features in renal transplantation, immunosuppressive drugs and their mechanisms of action and immunologically high risk transplantations such as ABO and HLA-incompatible transplantation. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): "allogenic response; allograft; immunosuppression; ABO incompatible transplantation; donor specific antibodies; HLA incompatible; desensitization; kidney transplantation". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 4717 articles. After reading titles and abstracts, 141 were included in the text, based on their relevance. RESULTS: The considerable step in comprehension and knowledge allogeneic response this last few years allowed a better used of immunosuppression and the discover of news immunosuppressive drugs. In the first part of this article, the allogeneic response will be described. The different classes of immunosuppressive drugs will be presented and the actual management of immunosuppression will be discussed. Eventually, the modalities and results of immunologically high-risk transplantations such as ABO and HLA incompatible transplantations will be reported. CONCLUSIONS: The knowledge and the control of allogeneic response to allogeneic graft allowed the development of renal transplantation. PMID- 27670825 TI - Epigenetic and genetic changes in soft tissue sarcomas: a review. AB - Soft tissue sarcomas are a versatile group of tumors with a proposed origin from mesenchymal stem cells. During recent years, the molecular biologic mechanisms behind the histogenesis of these tumors have become clearer. In addition to translocations and other genomic changes, epigenetic mechanisms have been shown to be greatly involved in the histogenesis of sarcomas as well as other cancers. Even though the molecular mechanisms behind sarcomas appear to be more complex than previously expected, epigenetic mechanisms bring new opportunities and means for the treatment of these complex diseases. PMID- 27670826 TI - Hyperpolarized 13 C,15 N2 -Urea MRI for assessment of the urea gradient in the porcine kidney. AB - PURPOSE: A decline in cortico-medullary osmolality gradient of the kidney may serve as an early indicator of pathological disruption of the tubular reabsorption process. The purpose of this study was to investigate the feasibility of hyperpolarized 13 C,15 N2 -urea MRI as a biomarker of renal function in healthy porcine kidneys resembling the human physiology. METHODS: Five healthy female Danish domestic pigs (weight 30 kg) were scanned at 3 Tesla (T) using a 13 C 3D balanced steady-state MR pulse sequence following injection of hyperpolarized 13 C,15 N2 -urea via a femoral vein catheter. Images were acquired at different time points after urea injection, and following treatment with furosemide. RESULTS: A gradient in cortico-medullary urea was observed with an intramedullary accumulation 75 s after injection of hyperpolarized 13 C,15 N2 urea, whereas images acquired at earlier time points postinjection were dominated by cortical perfusion. Furosemide treatment resulted in an increased urea accumulation in the cortical space, leading to a reduction of the medullary-to cortical signal ratio of 49%. CONCLUSION: This study demonstrates that hyperpolarized 13 C,15 N2 -urea MRI is capable of identifying the intrarenal accumulation of urea and can differentiate acute renal functional states in multipapillary kidneys, highlighting the potential for human translation. Magn Reson Med 76:1895-1899, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27670823 TI - The IASLC Mesothelioma Staging Project: Improving Staging of a Rare Disease Through International Participation. AB - For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma. In 1994, members of the International Mesothelioma Interest Group, in collaboration with the International Association for the Study of Lung Cancer, proposed a TNM staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer and the Union for International Cancer Control for the sixth editions of their staging manuals, this system has since been the international staging standard. However, it has significant limitations, particularly with respect to clinical staging and to the categories for lymph node staging. Here we provide an overview of the development of the International Association for the Study of Lung Cancer malignant pleural mesothelioma staging database, which was designed to address these limitations through the development of a large international data set. Analyses of this database, described in papers linked to this overview, are being used to inform revisions in the eighth editions of the American Joint Commission on Cancer and Union for International Cancer Control staging systems. PMID- 27670827 TI - Interactive patient blood management dashboards used in Western Australia. PMID- 27670828 TI - Atypical N-methyl-D-aspartate receptor encephalitis and a hippocampal tumour. PMID- 27670830 TI - A comment on Starcevic (2016) the case of food addiction. PMID- 27670829 TI - The borderline paradox. PMID- 27670831 TI - Paediatric bipolar disorder: What are the dangers of treating a hypothetical disorder as a real disease? PMID- 27670832 TI - Data transparency in clinical trials: Implications of Restoring Study 329. PMID- 27670833 TI - Commentary on Galletly et al. (2016), The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. PMID- 27670834 TI - Plasmonic Metasurfaces with Conjugated Polymers for Flexible Electronic Paper in Color. AB - A flexible electronic paper in full color is realized by plasmonic metasurfaces with conjugated polymers. An ultrathin large-area electrochromic material is presented which provides high polarization-independent reflection, strong contrast, fast response time, and long-term stability. This technology opens up for new electronic readers and posters with ultralow power consumption. PMID- 27670835 TI - Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease. AB - We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn's disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-alpha, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols. PMID- 27670836 TI - Crystal structure of nonphosphorylated receiver domain of the stress response regulator RcsB from Escherichia coli. AB - RcsB, the transcription-associated response regulator of the Rcs phosphorelay two component signal transduction system, activates cell stress responses associated with desiccation, cell wall biosynthesis, cell division, virulence, biofilm formation, and antibiotic resistance in enteric bacterial pathogens. RcsB belongs to the FixJ/NarL family of transcriptional regulators, which are characterized by a highly conserved C-terminal DNA-binding domain. The N-terminal domain of RcsB belongs to the family of two-component receiver domains. This receiver domain contains the phosphoacceptor site and participates in RcsB dimer formation; it also contributes to dimer formation with other transcription factor partners. Here, we describe the crystal structure of the Escherichia coli RcsB receiver domain in its nonphosphorylated state. The structure reveals important molecular details of phosphorylation-independent dimerization of RcsB and has implication for the formation of heterodimers. PMID- 27670837 TI - Investigations into the temporal development of epitheliocystis infections in brown trout: a histological study. AB - Epitheliocystis in Swiss brown trout (Salmo trutta) is a chlamydial infection, mainly caused by Candidatus Piscichlamydia salmonis and Candidatus Clavichlamydia salmonicola. To gain a better understanding of the temporal development of infections in wild brown trout, we investigated epitheliocystis infections during the course of the summer and autumn months of a single year (2015), and compared this to sampling points over the span of the years 2012-2014. The survey focused on tributaries (Venoge and Boiron) of the Rhone flowing in to Lake Geneva. When evaluated histologically, epitheliocystis infections were found throughout the period of investigation with the exception of the month of June. Fifty to 86 animals per sampling were investigated. Highest prevalence and infection intensities were seen in September. A correlation between epitheliocystis infection and water temperatures was not evident. Interyear comparison revealed consistent levels of prevalence and infection intensities in late summer. The absence of infections in June, combined with the consistent interyear results, indicates seasonal fluctuation of epitheliocystis infections in brown trout with a reservoir persisting during winter months from which infections can re-initiate each year. This could either be at levels below detection limits within the brown trout population itself or in an alternative host. PMID- 27670838 TI - Patterns of structural and defense investments in fine roots of Scots pine (Pinus sylvestris L.) across a strong temperature and latitudinal gradient in Europe. AB - Plant functional traits may be altered as plants adapt to various environmental constraints. Cold, low fertility growing conditions are often associated with root adjustments to increase acquisition of limiting nutrient resources, but they may also result in construction of roots with reduced uptake potential but higher tissue persistence. It is ultimately unclear whether plants produce fine roots of different structure in response to decreasing temperatures and whether these changes represent a trade-off between root function or potential root persistence. We assessed patterns of root construction based on various root morphological, biochemical and defense traits including root diameter, specific root length (SRL), root tissue density (RTD), C:N ratio, phenolic compounds, and number of phellem layers across up to 10 root orders in diverse populations of Scots pine along a 2000-km climatic gradient in Europe. Our results showed that different root traits are related to mean annual temperature (MAT) and expressed a pattern of higher root diameter and lower SRL and RTD in northern sites with lower MAT. Among absorptive roots, we observed a gradual decline in chemical defenses (phenolic compounds) with decreasing MAT. In contrast, decreasing MAT resulted in an increase of structural protection (number of phellem layers) in transport fine roots. This indicated that absorptive roots with high capacity for nutrient uptake, and transport roots with low uptake capacity, were characterized by distinct and contrasting trade-offs. Our observations suggest that diminishing structural and chemical investments into the more distal, absorptive roots in colder climates is consistent with building roots of higher absorptive capacity. At the same time, roots that play a more prominent role in transport of nutrients and water within the root system saw an increase in structural investment, which can increase persistence and reduce long-term costs associated with their frequent replacement. PMID- 27670839 TI - Tocilizumab-induced pancreatitis: case report and review of data from the FDA Adverse Event Reporting System. AB - WHAT IS KNOWN AND OBJECTIVE: Tocilizumab (TCZ) is a humanized monoclonal antibody acting against the IL-6 receptor. It is a drug used in the treatment of rheumatoid arthritis and can be either given intravenously every 4 weeks or subcutaneously once a week. Known adverse events (AE) associated with TCZ include: infections of the upper respiratory tract, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. Here, we present the first well documented case of TCZ-induced acute pancreatitis (AP) and a systematic review of the literature including data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Patient data collection was performed within the Berlin Case-Control Surveillance Study. A literature search for TCZ induced AP was conducted. Analysis of the FAERS database concerning TCZ associated pancreatic AE from the period of 2009 until the first quarter of 2013 was conducted. RESULTS AND DISCUSSION: A 40-year-old man presented with a 2-day history of progressive upper abdominal pain with elevated serum lipase and triglyceride levels. Biliary pancreatitis was ruled out by abdominal sonography and CT scan. Cessation of intravenously administered TCZ resulted in improvement of the patient's condition and a decline in elevated laboratory values, suggesting a probable relationship between TCZ intake and AP. Analysis of the FAERS database retrieved 52 cases of TCZ-associated AP that accounted for 70% of all pancreatic AE in association with TCZ use. Further literature search detected three additional cases in which TCZ use was associated with AP. WHAT IS NEW AND CONCLUSION: Physicians should be aware of the probable association between TCZ use and AP. Targeted post-authorization studies are needed to confirm and quantify the risk of TCZ-induced AP. PMID- 27670841 TI - Hyperexcitability of Mesencephalic Trigeminal Neurons and Reorganization of Ion Channel Expression in a Rett Syndrome Model. AB - People with Rett syndrome (RTT) have defects in motor function also seen in Mecp2 null mice. Motor function depends on not only central motor commands but also sensory feedback that is vulnerable to changes in excitability of propriosensory neurons. Here we report evidence for hyperexcitability of mesencephalic trigeminal (Me5) neurons in Mecp2-null mice and a novel cellular mechanism for lowering its impact. In in vitro brain slices, the Me5 neurons in both Mecp2-/Y male and symptomatic Mecp2+/- female mice were overly excitable showing increased firing activity in comparison to their wild-type (WT) male and asymptomatic counterparts. In Mecp2-/Y males, Me5 neurons showed a reduced firing threshold. Consistently, the steady-state activation of voltage-gated Na+ currents (INa ) displayed a hyperpolarizing shift in the Mecp2-null neurons with no change in the INa density. This seems to be due to NaV1.1, SCN1B and SCN4B overexpression and NaV1.2 and SCN3B under-expression. In contrast to the hyperexcitability, the sag potential and postinhibitory rebound (PIR) were reduced in Mecp2-null mice. In voltage-clamp, the IH density was deficient by ~33%, and the steady-state half activation had a depolarizing shift of ~10 mV in the Mecp2-null mice. Quantitative PCR analysis indicated that HCN2 was decreased, HCN1 was upregulated with no change in HCN4 in Mecp2-/Y mice compared to WT. Lastly, blocking IH reduced the firing rate much more in WT than in Mecp2-null neurons. These data suggest that the Mecp2 defect causes an increase in Me5 neuronal excitability likely attributable to alterations in INa , meanwhile IH is reduced likely altering neuronal excitability as well. J. Cell. Physiol. 232: 1151-1164, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27670840 TI - Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant. AB - Liver transplant is a treatment option for patients with MMA-emia. While this therapy does not bring about a complete cure, it is expected to prolong survival and improve the QOL of patients. The aim of this study was to evaluate the significance of LDLT for patients with MMA-emia in Japan. Clinical information on 13 patients with MMA-emia who underwent LDLT was acquired using a self-developed questionnaire sent to the doctors who provided medical care to patients with MMA emia after LDLT. Almost all of the patients continued on a protein-restricted diet, and the number of acidosis attacks had significantly decreased. Physical growth had recovered to within the normal range by 2.5 years after LDLT, especially in patients who underwent LDLT before the age of 1 year. The average propionyl carnitine (C3) level had significantly decreased after LDLT, and the DQs had not worsened. Liver transplant should be performed for MMA-emia in early life. This can be expected to maintain neurological development and improve the growth and QOL of patients. However, LDLT is not a curative treatment for MMA emia. A protein-restricted diet should be continued, and renal function should be monitored closely, with consideration of a renal transplant. PMID- 27670842 TI - Genetically encoded photocrosslinkers for identifying and mapping protein-protein interactions in living cells. AB - Protein-protein interactions (PPIs) play pivotal roles in regulation of many biological processes. Conventional methods are capable of investigating stable and strong interactions within protein complexes, but remain difficult for studying dynamic, transient, and weak PPIs. Herein we review photo-affinity unnatural amino acids that can be site-specifically incorporated into a protein of interest to covalently trap noncovalent PPIs under living conditions. A newly developed cleavable photocrosslinker from our group will also be introduced, which facilitated the prey-bait separation for better enrichment and identification of photocrosslinked PPI complexes. (c) 2016 IUBMB Life, 68(11):879 886, 2016. PMID- 27670843 TI - The Importance of a Maximum Threshold for Quality Indicators of a Breast Unit. PMID- 27670845 TI - Redefining dependency - a way forward. PMID- 27670844 TI - Monocytic MKP-1 is a Sensor of the Metabolic Environment and Regulates Function and Phenotypic Fate of Monocyte-Derived Macrophages in Atherosclerosis. AB - Diabetes promotes the S-glutathionylation, inactivation and subsequent degradation of mitogen-activated protein kinase phosphatase 1 (MKP-1) in blood monocytes, and hematopoietic MKP-1-deficiency in atherosclerosis-prone mice accelerates atherosclerotic lesion formation, but the underlying mechanisms were not known. Our aim was to determine the mechanisms through which MKP-1 deficiency in monocytes and macrophages promotes atherogenesis. Transplantation of MKP-1 deficient bone marrow into LDL-R-/- (MKP-1LeuKO) mice accelerated high-fat diet (HFD)-induced atherosclerotic lesion formation. After 12 weeks of HFD feeding, MKP-1LeuKO mice showed increased lesion size in both the aortic root (1.2-fold) and the aorta (1.6-fold), despite reduced plasma cholesterol levels. Macrophage content was increased in lesions of MKP-1LeuKO mice compared to mice that received wildtype bone marrow. After only 6 weeks on a HFD, in vivo chemotactic activity of monocytes was already significantly increased in MKP-1LeuKO mice. MKP 1 deficiency in monocytes and macrophages promotes and accelerates atherosclerotic lesion formation by hyper-sensitizing monocytes to chemokine induced recruitment, predisposing macrophages to M1 polarization, decreased autophagy and oxysterol-induced cell death whereas overexpression of MKP-1 protects macrophages against metabolic stress-induced dysfunction. MKP-1 serves as a master-regulator of macrophage phenotype and function and its dysregulation by metabolic stress may be a major contributor to atherogenesis and the progression of atherosclerotic plaques. PMID- 27670846 TI - 3D Quantification of Low-Coordinate Surface Atom Density: Bridging Catalytic Activity to Concave Facets of Nanocatalysts in Fuel Cells. AB - A protocol to quantify the distribution of surface atoms of concave nanocatalysts according to their coordination number is proposed. The 3D surface of an Au@Pd concave nanocube is reconstructed and segmented. The crystallographic coordinates and low-coordinate surface atom densities of the concave facets are determined. The result shows that 32% of the surface atoms are low-coordinated, which may contribute to the high activity. PMID- 27670847 TI - Staging research of human lung cancer tissues by high-resolution magic angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS 1 H NMR) and multivariate data analysis. AB - AIM: High-resolution magic-angle spinning proton nuclear magnetic resonance (HRMAS 1 H NMR) spectroscopy technique was employed to analyze the metabonomic characterizations of lung cancer tissues in hope to identify potential diagnostic biomarkers for malignancy detection and staging research of lung tissues. METHODS: HRMAS 1 H NMR spectroscopy technique can rapidly provide important information for accurate diagnosis and staging of cancer tissues owing to its noninvasive nature and limited requirement for the samples, and thus has been acknowledged as an excellent tool to investigate tissue metabolism and provide a more realistic insight into the metabonomics of tissues when combined with multivariate data analysis (MVDA) such as component analysis and orthogonal partial least squares-discriminant analysis in particular. RESULTS: HRMAS 1 H NMR spectra displayed the metabonomic differences of 32 lung cancer tissues at the different stages from 32 patients. The significant changes (P < 0.05) of some important metabolites such as lipids, aspartate and choline-containing compounds in cancer tissues at the different stages had been identified. Furthermore, the combination of HRMAS 1 H NMR spectroscopy and MVDA might potentially and precisely provided for a high sensitivity, specificity, prediction accuracy in the positive identification of the staging for the cancer tissues in contrast with the pathological data in clinic. CONCLUSION: This study highlighted the potential of metabonomics in clinical settings so that the techniques might be further exploited for the diagnosis and staging prediction of lung cancer in future. PMID- 27670848 TI - The role of older siblings in infant motor development. AB - Previous research has suggested that infant motor skills may be affected by older siblings but has not considered whether this is due to specific characteristics of the older sibling or of the quality of the sibling relationship. The current study used a longitudinal diary method to record infant motor milestones from 23 infants with older siblings along with parent reports and standardized assessments of motor skills. Parent reports of the older siblings' motor skills and the sibling relationship were also collected until the infants were 18months old. The motor skills, age, and sex of the older siblings were not significantly related to any measure of infant motor development. A significant correlation was revealed between perceived agonism between siblings and infant fine motor skills at 18months, suggesting the importance of considering reciprocal effects of motor development on sibling relationships. Overall, the suggestion that older siblings may provide a good model of motor skills for infants is not supported by the current data. In the future, it will be important to assess the dynamic interactions between different factors in predicting infant motor development, allowing early identification of motor difficulties, which could affect other areas of cognitive development and health. PMID- 27670849 TI - Identifying and removing the cell-cycle effect from single-cell RNA-Sequencing data. AB - Single-cell RNA-Sequencing (scRNA-Seq) is a revolutionary technique for discovering and describing cell types in heterogeneous tissues, yet its measurement of expression often suffers from large systematic bias. A major source of this bias is the cell cycle, which introduces large within-cell-type heterogeneity that can obscure the differences in expression between cell types. The current method for removing the cell-cycle effect is unable to effectively identify this effect and has a high risk of removing other biological components of interest, compromising downstream analysis. We present ccRemover, a new method that reliably identifies the cell-cycle effect and removes it. ccRemover preserves other biological signals of interest in the data and thus can serve as an important pre-processing step for many scRNA-Seq data analyses. The effectiveness of ccRemover is demonstrated using simulation data and three real scRNA-Seq datasets, where it boosts the performance of existing clustering algorithms in distinguishing between cell types. PMID- 27670850 TI - Differences between the United States and Japan in labels of oncological drugs. AB - PURPOSE: Our study addresses how the information in the labels differed between United States (US) and Japan, what factors were associated with the decision to place the boxed warning on the label, and the relation of both countries in terms of drug label policy. METHODS: We investigated adverse drug reactions (ADRs) in boxed warnings for 44 oncological drug labels approved from 2004 to 2014 in both Japan and the US. We applied conditional logistic regression to examine how likely it was for each ADR to be included in a boxed warning. RESULTS: There were substantial differences in all sections of the labels. The concordance rate between US and Japanese labels was 44.1% for serious adverse reactions and 30.5% for boxed warnings. Our regression analysis indicated that deaths and/or terminations related to specific ADRs reported in clinical trials were significantly associated with inclusion of the ADR in boxed warnings in Japan, but not in the US. The boxed warnings of similar drugs seemed to affect those of follow-on drugs in both countries. US drug labels were likely to influence Japanese labels, but not vice versa. CONCLUSION: This study suggests that the observed differences are not solely due to differences in clinical outcomes between the two countries, but rather due to differences in regulatory considerations and historical factors in both local and global contexts. Further research is needed to examine the impact of these differences on public health and to determine how and to what extent we should intervene with this status quo. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27670851 TI - Comparison of shockwave frequencies of 30 and 60 shocks per minute for kidney stones: a prospective randomized study. AB - OBJECTIVE: One of the factors that determines the treatment success of shockwave lithotripsy (SWL) is the frequency of the shockwaves during the procedure. This study compared the efficacy and pain perception of shockwave frequencies at 30 versus 60 shocks/min for kidney stones. MATERIALS AND METHODS: From August 2013 to May 2015, 160 patients with solitary, radiopaque kidney stones were randomized to SWL at 30 shocks/min (group 1) or 60 shocks/min (group 2), with 80 patients in each group. The primary outcome measure was success rate at 3 months after the last SWL session. The secondary outcome measure was pain perception during the procedures. RESULTS: Of the 160 randomized patients, data for a total of 148 patients (74 patients in group 1 and 74 patients in group 2) were analyzed, after the exclusion of the patients lost to follow-up or who required secondary intervention within 3 months. There was no statistically significant difference between the two groups in terms of the success rate at 3 months (68.9% vs 71.6%, p = .719). However, the mean visual analogue scale scores of all the sessions were significantly higher in group 1 than in group 2 (5.83 vs 4.06, p < .05). Stone location, especially the lower calyceal location, was the only significant negative predictor for success according to multivariate logistic regression analysis. CONCLUSIONS: The success rate was similar between these two frequencies. However, pain perception was significantly higher at 30 than at 60 shocks/min. PMID- 27670852 TI - Next Generation Sequencing of Pooled Samples: Guideline for Variants' Filtering. AB - Sequencing large number of individuals, which is often needed for population genetics studies, is still economically challenging despite falling costs of Next Generation Sequencing (NGS). Pool-seq is an alternative cost- and time-effective option in which DNA from several individuals is pooled for sequencing. However, pooling of DNA creates new problems and challenges for accurate variant call and allele frequency (AF) estimation. In particular, sequencing errors confound with the alleles present at low frequency in the pools possibly giving rise to false positive variants. We sequenced 996 individuals in 83 pools (12 individuals/pool) in a targeted re-sequencing experiment. We show that Pool-seq AFs are robust and reliable by comparing them with public variant databases and in-house SNP genotyping data of individual subjects of pools. Furthermore, we propose a simple filtering guideline for the removal of spurious variants based on the Kolmogorov Smirnov statistical test. We experimentally validated our filters by comparing Pool-seq to individual sequencing data showing that the filters remove most of the false variants while retaining majority of true variants. The proposed guideline is fairly generic in nature and could be easily applied in other Pool seq experiments. PMID- 27670853 TI - Recovery of sit-to-stand function in patients with intensive-care-unit-acquired muscle weakness: Results from the General Weakness Syndrome Therapy cohort study. AB - OBJECTIVES: To describe the time course of recovery of sit-to-stand function in patients with intensive-care-unit-acquired muscle weakness and the impact of recovery. METHODS: A cohort study in post-acute intensive care unit and rehabilitation units. Patients with chronic critical illness and intensive-care unit-acquired muscle weakness were included. Sit-to-stand function was measured daily, using a standardized chair height, defined as 120% of the individual's knee height. RESULTS: A total of 150 patients were recruited according to the selection criteria. The primary outcome of independent sit-to-stand function was achieved by a median of 56 days (interquartile range Q1-Q3 = 32-90 days) after rehabilitation onset and a median of 113 days (Q1-Q3=70-148 days) after onset of illness. The final multivariate model for recovery of sit-to-stand function included 3 variables: age (adjusted hazard ratio (HR) = 0.96 (95% CI 0.94-0.99), duration of ventilation (HR=0.99 (95% CI 0.98-1.00) and Functional Status Score for the Intensive Care Unit (FSS-ICU) (adjusted HR=1.12 (95% CI 1.08-1.16)). CONCLUSION: Rapid recovery of sit-to-stand function for most patients with intensive-care-unit-acquired muscle weakness were seen. The variables older age and longer duration of ventilation decreased, and higher FSS-ICU increased the chance of regaining independent sit-to-stand function. PMID- 27670854 TI - Individual and Contextual Determinants of Social Homecare Usage in Slovenia. AB - THEORY: Social homecare is important for older people, as it enables them to remain in their own homes during worsening health, thus relieving the burden on institutional facilities such as homes for the elderly or nursing homes and hospitals. METHOD: A representative survey of social homecare users was employed to assess determinants of the scope of social homecare in Slovenia. Multiple regression analysis was used to evaluate determinants defined by Andersen's behavioral model that affect the scope of social homecare. RESULTS: As expected, need (Functional impairment B = .378, P = 0.000) was the most important explanatory component, followed by availability of informal care network (Lives alone B = -.136, P = 0.000; Has children B = - .142; P = 0.000) and other contextual factors such as total costs of the services (B = -.075; P = 0.003) and temporal availability of services (B=-.075, P=0.012). The model explained 18% of variability in the scope of social homecare. CONCLUSION: This study showed that data on the individual level, as opposed to data on an aggregated level, show different determinants of social homecare utilization. Moreover, the results showed that social homecare is especially important in two circumstances: when older people have a high level of need and when they do not have access to informal care networks. Contextual factors had a moderate effect on the scope of social homecare, which shows universal access to the latter at the individual level. PMID- 27670856 TI - Defensive medicine and overutilization of imaging-an issue of radiation protection. PMID- 27670857 TI - Fever of unknown origin (FUO) revised. AB - Fever of unknown origin (FUO) was originally characterised in 1961 by Petersdorf and Beeson as a disease condition of temperature exceeding 38.3 degrees C on at least three occasions over a period of at least three weeks, with no diagnosis made despite one week of inpatient investigation. However, since underlying diseases are often reported for classical FUO, these presentations may not be considered to be of "unknown origin". Rather, the aetiology of prolonged fever may resolve, or not resolve. The definition of fever with unresolved cause (true FUO) is difficult, as it is a moving target, given the constant advancement of imaging and biomarker analysis. Therefore, the prevalence of fever with unresolved cause (FUO) is unknown.In this review, we report such a case of prolonged fever, which initially has presented as classical FUO, and discuss current literature. Furthermore, we will give an outlook, how a prospective study on FUO will allow to solve outstanding issues like the utility of different diagnostic investigations, and the types and prevalence of various underlying diseases. PMID- 27670858 TI - Impact of gender on tumor stage and survival of upper urinary tract urothelial cancer : A population-based study. AB - BACKGROUND: The aim of this study was to analyze the impact of gender on tumor stage, overall and cancer-specific mortality of upper urinary tract urothelial cancer (UTUC) in a population-based, nationwide analysis. METHODS: All Austrian patients with UTUC diagnosed between 1983 and 2010 were included in this study. Overall mortality was estimated by the Kaplan-Meier method. Cancer-specific (UTUC) mortality was estimated by cumulative incidence with mortality due to other causes as a competing risk. The effect of age was adjusted in a descriptive as well as a statistical inferential way. RESULTS: This study included 2066 patients (men n = 1169, mean age 68.3 +/-11.5 years, women n = 897, 72.6 +/-10.4 years). Tumor stage distribution was as follows: pT1: men n = 411, women n = 268, pT2: men n = 263, women n = 187, pT3: men n = 382, women n = 328 and pT4: men n = 113, women n = 114. The male:female ratio continuously declined from 1.5 for pT1 tumors to 1.4 for pT2 tumors, 1.2 for pT3 tumors and 1.0 for pT4-tumors. In the entire cohort the 5-year cumulative overall mortality was 57 % for women versus 50 % for men (p = 0.0002). For pT1 (women 33 %, men 31 %) and pT2 stage tumors (women 45 %, men 45 %) the 5-year overall mortality was comparable between both sexes. In pT3 (women 68 %, men 62 %) and pT4 (women 95 %, men 87 %) tumors women had a higher overall mortality rate. The 5-year cancer-specific mortality (CSM) of the entire cohort was 12 % for women and 10 % for men (p = 0.067): pT1 women 5 % men 3 %, pT2 women 9 % men 10 %, pT3 women 14 % men 11 % and pT4 women 29 % men 27 %. CONCLUSIONS: In this population-based nationwide analysis, sex differences were notable for UTUC. Women tended to have more advanced tumor stages at diagnosis and a higher overall and cancer-specific mortality in advanced tumor stages. PMID- 27670859 TI - 40. Jahrestagung der Osterreichischen Gesellschaft fur Pneumologie. Wien, 6.-8. Oktober 2016. PMID- 27670855 TI - Frailty and sarcopenia in elderly. AB - Frailty is a pre-disability syndrome where an older person can be identified as being at risk when exposed to stressors associated with high risk for disability or needing to be hospitalized. Two major frailty definitions exist. The physical phenotype of frailty and the multiple deficit model. A simple frailty screening tool-FRAIL-has been validated. Treatment of frailty involves resistance exercise, optimization of nutrition, and treatment of fatigue (sleep apnea, depression), treatable causes of weight loss and adjustment of polypharmacy. Sarcopenia (decline in function with low muscle mass) is a major cause of frailty. A simple sarcopenia screening tool-SARC-F-has been validated. The multiple causes of sarcopenia are reviewed. Optimal treatment is resistance exercise, leucine enriched essential amino acids and vitamin D replacement. PMID- 27670860 TI - Occurrence and Biological Effects of Endocrine Disrupting Chemicals in the Yellow River (Zhengzhou Section). AB - Estrogenic activities of river water from four representative cross-sections of the Yellow River (Zhengzhou section) and their effects on reproduction and development of fish were assessed. MVLN assay showed estradiol equivalents of river water from Yiluohe, Xinmanghe, Qinhe and Huayuankou cross-sections were 1.09 +/- 0.11, 0.72 +/- 0.01, 1.19 +/- 0.19 and 0.80 +/- 0.04 ng/L, respectively. Significant vitellogenin (VTG) inductions were observed in adult male Japanese madaka (Oryzias latipes) after 30 days of exposure to river water from Yiluohe and Qinhe cross-sections (p < 0.05). Hepatic-somatic index was significantly elevated in fish exposed to water from Qinhe cross-section (p < 0.05). A significant delay in time to hatching was observed in embryos treated by water from Xinmanghe cross-section (p < 0.05). Significant lower survivals were observed in fish treated by water from Yiluohe and Xinmanghe cross-sections after a full life cycle exposure (p < 0.05). Exposure of water from Yiluohe and Qinhe cross-sections induced significantly elevated VTG levels in the first sexually mature male fish (p < 0.05). Both the in vitro and in vivo bioassay demonstrate endocrine disrupting chemicals exist in the Yellow River (Zhengzhou section) and fish in Yiluohe and Qinhe cross-sections can be at a risk of reproductive and developmental impairment. PMID- 27670862 TI - BMA considers plans after suspending junior doctor strikes. PMID- 27670861 TI - Dynamics of Aromatase and Physiological Indexes in Male Fish as Potential Biomarkers of Anthropogenic Pollution. AB - Endocrine disruption on aquatic wildlife is being increasingly reported, and the changes in gene aromatase expression are used as indicators. However, natural fluctuations in brain and gonadal aromatase expression and physiological indexes have not been previously measured in a fish species (Jenynsia multidentata) throughout a complete reproductive cycle, nor the biological effects of anthropogenic inputs on these responses. Accordingly, males were monthly collected over a year in both, a reference and a contaminated site. Physicochemical analyses of water samples were done and reflected a strong anthropogenic impact. Brain aromatase fluctuates along the reproductive cycle of this species and, noticeably, the increase of brain gene expression begins with a 1 month delay in the contaminated site. This mismatch is also evidenced for testes weight. Hepatosomatic index also revealed adverse effects in the polluted site. In turn, the alterations observed in biological responses could be affecting the reproduction of this fish species. PMID- 27670863 TI - Effect of low-impact aerobic exercise combined with music therapy on patients with fibromyalgia. A pilot study. AB - OBJECTIVE: Fibromyalgia is a pathological entity characterized by chronic widespread musculoskeletal pain and the presence of "tender points". It constitutes a significant health problem because of its prevalence and economic impact. The aim of the present study was to determine the therapeutic benefits of low impact aerobic exercise alone or in combination with music therapy in patients with fibromyalgia. METHODS: A single-blind randomized controlled pilot trial was performed. Thirty-five individuals with fibromyalgia were divided into three groups: (G1) therapeutic aerobic exercise with music therapy (n=13); (G2) therapeutic aerobic exercise at any rhythm (n=13) and (CG) control (n=9). The intervention period lasted eight weeks. Depression, quality of life, general discomfort and balance were assessed before and after intervention. RESULTS: At post-intervention, group G1 improved in all variables (depression (p=0.002), quality of life (p=0.017), general discomfort (p=0.001), and balance (p=0.000)), while group G2 improved in general discomfort (p=0.002). The change observed in balance was statistically different between groups (p=0.01). CONCLUSION: Therapeutic aerobic exercise is effective in improving depression and general discomfort in individuals with fibromyalgia. However, effectiveness is higher when combined with music therapy, which brings about further improvements in quality of life and balance. PMID- 27670864 TI - Short-term effects of traditional Thai massage on electromyogram, muscle tension and pain among patients with upper back pain associated with myofascial trigger points. AB - OBJECTIVE: To investigate effects of traditional Thai massage (TTM) on electromyographic (EMG) activity, muscle tension and pain intensity in patients with upper back pain associated with myofascial trigger points (MTrPs). DESIGN: A single-blind, randomized clinical trial. SETTING: The Department of Physical Therapy, School of Health Science, Mae Fah Luang University, Thailand. INTERVENTION: Fifty patients were randomly assigned to receive a 30-min session of either TTM or control (sham microwave diathermy). OUTCOMES: Electromyogram (EMG), Muscle tension rating, and pain intensity rating RESULTS: TTM were associated with significant decreases in EMG, muscle tension and pain intensity after the end of treatment session (p<0.05). For all outcomes, similar changes were not observed in the control group (p>0.05) except for muscle tension (p<0.05). In addition, there was a significantly greater reduction in all parameters for the TTM group when compared with the control group. CONCLUSION: We therefore suggest that TTM can increase physical relaxation and reduce pain in patients with upper back pain associated with MTrPs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02067325. PMID- 27670865 TI - A mindfulness-based intervention to control weight after bariatric surgery: Preliminary results from a randomized controlled pilot trial. AB - OBJECTIVE: This study aimed to develop and test a novel mindfulness-based intervention (MBI) designed to control weight after bariatric surgery. DESIGN: Randomized, controlled pilot trial. SETTING: Beth Israel Deaconess Medical Center, Boston, MA, USA. INTERVENTIONS: Bariatric patients 1-5 years post-surgery (n=18) were randomized to receive a 10-week MBI or a standard intervention. MAIN OUTCOME MEASURES: Primary outcomes were feasibility and acceptability of the MBI. Secondary outcomes included changes in weight, eating behaviors, psychosocial outcomes, and metabolic and inflammatory biomarkers. Qualitative exit interviews were conducted post-intervention. Major themes were coded and extracted. RESULTS: Attendance was excellent (6 of 9 patients attended >=7 of 10 classes). Patients reported high satisfaction and overall benefit of the MBI. The intervention was effective in reducing emotional eating at 6 months (-4.9+/-13.7 in mindfulness vs. 6.2+/-28.4 in standard, p for between-group difference=0.03) but not weight. We also observed a significant increase in HbA1C (0.34+/-0.38 vs. -0.06+/-0.31, p=0.03). Objective measures suggested trends of an increase in perceived stress and symptoms of depression, although patients reported reduced stress reactivity, improved eating behaviors, and a desire for continued mindfulness-based support in qualitative interviews. CONCLUSIONS: This novel mindfulness-based approach is highly acceptable to bariatric patients post-surgery and may be effective for reducing emotional eating, although it did not improve weight or glycemic control in the short term. Longer-term studies of mindfulness-based approaches may be warranted in this population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02603601. PMID- 27670866 TI - A mindful eating intervention: A theory-guided randomized anti-obesity feasibility study with adolescent Latino females. AB - While pediatric anti-obesity lifestyle interventions have received considerable attention, few show sustained impact on body mass index (BMI). Using the Information-Motivation-Behavioral Skills Theory as a framework, we examined the effects of a satiety-focused mindful eating intervention (MEI) on BMI, weight and mindful awareness. METHOD: DESIGN AND SETTING: Utilizing a two-group, repeated measures design, 37 adolescent females with a BMI >90th percentile, recruited from a public high school in a Latino community in the Southwestern United States, were randomized 2:1, one third to the group receiving a 6-week MEI and two thirds to the comparison group (CG) receiving the usual care (nutrition and exercise information). INTERVENTION: During six weekly 90-min after school MEI group sessions, the behavioral skills of slow intentional eating were practiced with foci on satiety cues and triggers to overeat. OUTCOMES: Feasibility and acceptability were measured as participant retention (goal >=55%) and evaluative comments from those in the MEI group, respectively. BMI and mindful awareness were measured on site at baseline, immediately post intervention, and at 4-week follow-up (week 10). RESULTS: Fifty-seven and 65% of those in the MEI and CG were retained throughout the study, respectively. MEI participants showed significantly lowered BMI compared with CG participants, whose weight increased (p<0.001). At six weeks, the MEI group BMI decreased by 1.1kg/m(2) (BMI continued to decline to 1.4kg/m(2) by week 10); while CG BMI increased by 0.7kg/m(2) (consistent with BMI >90th percentile standard growth projections). CONCLUSIONS: Initial and sustained decline of BMI in the MEI group supports further study of this theory-guided approach, and the value of practicing satiety-focused mindful eating behavioral skills to facilitate health behavior change. PMID- 27670867 TI - Expected and perceived efficacy of complementary and alternative medicine: A comparison views of patients with cancer and oncologists. AB - BACKGROUND & AIMS: This study sought to identify discrepancies between the expectations of patients with cancer and oncologists regarding the efficacy of complementary and alternative medicines (CAMs), and to determine how patients evaluate CAM efficacy after its use. METHODS: Data from the Cancer Patient Experience Study, a nationwide survey, were used. Seven subdivided efficacy domains were included in the survey. An oncologist-patient matching analysis was done to assess the concordance of CAM efficacies between oncologists and patients with cancer. In addition, the patients' expectations of CAM efficacies were compared before and after use. RESULTS: Out of 719 participants, 201 patients with cancer (28.0%) reported using CAMs. The patients with cancer generally tended to be more positive about CAM efficacies than the oncologists. The largest discrepancy in efficacy perception was found in the efficacy domain of survival benefit, which included complete disease remission and prolonged survival. Many patients reported that they did not experience the positive efficacy they had anticipated before use. However, a substantial proportion of patients indicated that CAMs were as effective as they had expected, even though there is little evidence supporting the CAM efficacies. CONCLUSIONS: There was a marked discrepancy and a lack of concordance in expectations of CAM efficacy between patients with cancer and oncologists. Better communication between the patients and oncologists regarding CAM efficacy would be needed to make the patients to have shared expectations, and to reduce unnecessary CAM use. PMID- 27670868 TI - Physiological and psychological responses of humans to the index of greenness of an interior space. AB - The objective of this study was to identify the optimal index of greenness in terms of psychophysiological responses and subjective preference. We recruited 103 adult (51 male, 52 female) participants, who were examined individually in an interior space (lab) setting at Konkuk University, Seoul, South Korea. Participants observed plants in the space for 3min per experimental index of greenness (5%, 20%, 50%, and 80%). During this period, heart rate variability (HRV) and electroencephalographic (EEG) physiological responses were measured, and the participant's preference for index of greenness and subjective index of greenness was determined via surveys. HRV values were normal, and not significantly different, except that male participants showed higher mean variability between cardiac NN intervals and greater autonomic activity than female participants (P<0.05). EEG data were not significantly different, except that female participants had a significantly higher mean amplitude at the left occipital (O1) electrode than male participants (P<0.01). Subjectively, participants preferred the 50% index of greenness the most, though they consistently reported the subjective index of greenness to be ~15% higher than the actual level. We conclude that given a limited interior space, even a small amount of greenery may exert a relaxing effect on people. PMID- 27670869 TI - "Merging Yoga and Occupational Therapy (MY-OT): A feasibility and pilot study". AB - OBJECTIVE: To examine the feasibility and benefits of the Merging Yoga and Occupational Therapy (MY-OT) intervention. DESIGN: This is the primary analysis of a non-controlled pretest-posttest pilot study to understand the feasibility and impact of MY-OT on balance, balance self-efficacy, and fall risk factor management in people with chronic stroke. SETTING: University research laboratory. PARTICIPANTS: People with chronic stroke were included in the study if they: had sustained a fall or had fear of falling, were able to stand, and hand impaired balance and were at risk for falls (<=46 on the Berg Balance Scale (BBS)). INTERVENTIONS: Individuals completed an 8 week intervention that included 16 sessions of both yoga and group occupational therapy (OT). Yoga included physical postures, breathing exercises, and meditation. OT focused on post-stroke fall risk factor management. MAIN OUTCOME MEASURES: The BBS was used to assess balance, the Activities-specific Balance Confidence Scale (ABC) was used to measure balance self-efficacy. Five fall risk factor management scales were used. RESULTS: Overall, the intervention was considered feasible, as individuals were able to safely complete the intervention with little attrition and high attendance. Balance improved by 30% (p=0.002). Balance self-efficacy improved by 15% (p=0.034). Each of the five fall risk factor management scales improved, but only two significantly improved (Fall Prevention and Management Questionnaire, 29%, p=0.004 and Fall Prevention Strategy Survey, 42%, p=0.032). CONCLUSION: The results demonstrate that MY-OT is a potential intervention to improve multiple fall related outcomes for people with stroke. Therapists may consider these interventions for people with stroke, but additional research is warranted. PMID- 27670872 TI - Core therapies in medicine: Environmental health. PMID- 27670871 TI - The effect of yoga practice on glycemic control and other health parameters in Type 2 diabetes mellitus patients: A systematic review and meta-analysis. PMID- 27670870 TI - CAM use in recently-returned OEF/OIF/OND US veterans: Demographic and psychosocial predictors. AB - OBJECTIVES: Because the use of complementary and alternative medicine (CAM) is increasing among veterans, understanding more about the characteristics of veterans who use CAM is increasingly important. Studies reporting on predictors of use almost always discuss CAM in the aggregate, yet each CAM modality represents a unique approach to healthcare, and each may have different correlates as well as different effectiveness. Very little information is available about veterans' use of each distinct modality, and about psychosocial correlates of various forms of CAM use. DESIGN: We analyzed data from wave 1 of the Survey of the Experiences of Returning Veterans (SERV) Study, which included 729 veterans returning from Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF) and Operation New Dawn (OND). SETTING: Data were collected by telephone interviews. MAIN MEASURES: We examined a range of potentially important correlates of CAM use, including demographics, military experiences, and current mental and physical health. RESULTS: Each predictor related to a unique constellation of CAM modalities; not one of the predictors examined was associated with more than half of the 12 modalities. For example, women were more likely to use acupuncture, massage, yoga, meditation and spiritual healing, and age related only to greater use of homeopathy, while deployment injuries related positively to use of chiropractic, nutrition and meditation. CONCLUSIONS: Results suggest that in order to understand CAM use, CAM modalities should be considered unique and separate practices. This greater understanding should be useful for future health service provision for veterans. PMID- 27670873 TI - Metaphorical mapping between raw-cooked food and strangeness-familiarity in Chinese culture. AB - Previous research has demonstrated metaphorical mappings between physical coldness-warmth and social distance-closeness. Since the concepts of interpersonal warmth are frequently expressed in terms of food-related words in Chinese, the present study sought to explore whether the concept of raw-cooked food could be unconsciously and automatically mapped onto strangeness familiarity. After rating the nutritive value of raw or cooked foods, participants were presented with morphing movies in which their acquaintances gradually transformed into strangers or strangers gradually morphed into acquaintances, and were asked to stop the movies when the combined images became predominantly target faces. The results demonstrated that unconscious and automatic metaphorical mappings between raw-cooked food and strangeness familiarity exist. This study provides a foundation for testing whether Chinese people can think about interpersonal familiarity using mental representations of raw-cooked food and supports cognitive metaphor theory from a crosslinguistic perspective. PMID- 27670874 TI - Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence Accelerated Mouse Prone 8 Mice. AB - OBJECTIVE: To investigate the preventive treatment effects of electroacupuncture (EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: The 5-month-old male SAMP8 and age-matched homologous normal aging mice (SAMR1) were adopted in this study. EA stimulation at Baihui (GV 20) and Yintang (EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-beta (A beta) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. RESULTS: After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, A beta expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. CONCLUSION: EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting A beta containing aggregates. PMID- 27670875 TI - A Clinical Observation of Functional Abdominal Pain Syndrome in Patients Treated by Traditional Chinese Spinal Orthopedic Manipulation. AB - OBJECTIVE: To evaluate the clinical effect of traditional Chinese spinal orthopedic manipulation (TCSOM) in treating patients with functional abdominal pain syndrome (FAPS) in comparison with Pinaverium Bromide (Dicetel, PBD), and to assess a possible cause for FAPS. METHODS: Eighty patients with FAPS were randomly and equally assigned to the TCSOM group and PBD group according to the random number table. All patients in the TCSOM group were treated with a maximum of 5 times of spinal manipulations. Patients in the PBD group were instructed to take 50 mg 3 times a day, consistently for 2 weeks. The symptoms of pre- and post treatment were assessed on a visual analog scale (VAS) pain score. A symptom improvement rating (SIR) was implemented to evaluate the effects of the treatments. RESULTS: The symptoms of 27 cases of the TCSOM group were relieved soon after the first TCSOM treatment and 9 cases were significantly improved. The VAS pain scores in the TCSOM group were significantly lower than those in the PBD group after 2 weeks treatment. According to the SIR based on VAS, the TCSOM group included 30 cases with excellent results, 7 cases with good, and 3 cases with poor. Adverse events to the treatment were not reported. Based on VAS, the PBD group reported 8 cases with excellent results, 10 cases with good and 22 cases with poor. There was a significant difference between the two groups (P<0.01). CONCLUSIONS: The displacement of intervertebral discs and/or vertebra in the thoracic or lumbar region seems to be a contributing factor in the symptoms of FAPS. TCSOM is an effective treatment for FAPS. PMID- 27670876 TI - Single minimal incision fasciotomy for the treatment of chronic exertional compartment syndrome: outcomes and complications. AB - INTRODUCTION: Chronic exertional compartment syndrome (CECS) is a common injury in young athletes, causing pain in the involved leg compartment during strenuous exercise. The gold standard treatment is fasciotomy, but most of the reports on its effectiveness include relatively small cohorts and relatively short follow-up periods. This study reports the long-term results of a large cohort of young athletes who underwent single-incision fasciotomy for CECS. MATERIALS AND METHODS: This a retrospective case-series study. All patients treated by fasciotomies performed for CECS between 2007 and 2011, in a tertiary medical institution. CECS was diagnosed following history taking and clinical evaluation, and confirmed by compartment pressure measurements. Ninety-five legs that underwent single-incision subcutaneous fasciotomy were included. Data on the numerical analog scale (NAS), Tegner activity score, and quality-of-life (QOL) as measured via the short form-12 (SF-12) were retrieved from all patients preoperatively and at the end of follow-up. RESULTS: The average time to diagnosis was 22 months and the mean follow-up was 50.1 months. Sixty-three legs underwent anterior compartment fasciotomy (an additional 30 legs also underwent lateral compartment release), and two legs underwent lateral and peroneal compartment releases. The average change in Tegner score was an improvement of 14.6 points. Similarly, the patients reported a significant improvement in the SF 12 and NAS scores. Satisfaction rates were high (average 75.5 %). The main complications were wound infection (2 patients) and nerve injuries (4 patients). Eight patients had recurrence. CONCLUSION: Single-incision fasciotomy leads to long-term improvement in the activity level and QOL of patients with CECS. PMID- 27670877 TI - Comparison of prone vs. supine unenhanced CT imaging in patients with clinically suspected ureterolithiasis. AB - PURPOSE: To retrospectively evaluate whether prone CT scanning is superior to supine scanning for correct localization of distal urinary calculi in patients with acute flank pain. METHODS: Consecutively performed unenhanced CT scans in patients with acute flank pain were retrospectively analyzed in 150 patients in supine and another 150 patients in prone position. Images were reviewed by two radiologists on consensus. Findings in both groups were compared using two-sided Fisher Exact tests and Wilcoxon-Mann-Whitney test. RESULTS: Urinary calculi were found in 67% of patients in each group. In the supine scanning group, there were 16 cases, in which the location of the stone was equivocal being either located intramurally at the ureterovesical junction (UVJ) or having already passed into the bladder. In contrast, in the prone imaging group all distal stones could be allocated accurately, either to the intramural UVJ or the urinary bladder (37 intramural UVJ stones and six bladder stones in prone scanning group vs. 21 intramural UVJ stones and one bladder stone when scanned supine). CONCLUSION: Prone scanning is superior to supine CT scanning for acute flank pain to accurately distinguish intramural UVJ stones from stones that have already passed into the bladder, a distinction which influences patient management. PMID- 27670878 TI - Commentary regarding a recent collaborative consensus statement addressing prostate MRI and MRI-targeted biopsy in patients with a prior negative prostate biopsy. PMID- 27670879 TI - CARD9 negatively regulates NLRP3-induced IL-1beta production on Salmonella infection of macrophages. AB - Interleukin-1beta (IL-1beta) is a proinflammatory cytokine required for host control of bacterial infections, and its production must be tightly regulated to prevent excessive inflammation. Here we show that caspase recruitment domain containing protein 9 (CARD9), a protein associated with induction of proinflammatory cytokines by fungi, has a negative role on IL-1beta production during bacterial infection. Specifically, in response to activation of the nucleotide oligomerization domain receptor pyrin-domain containing protein 3 (NLRP3) by Salmonella infection, CARD9 negatively regulates IL-1beta by fine tuning pro-IL-1beta expression, spleen tyrosine kinase (SYK)-mediated NLRP3 activation and repressing inflammasome-associated caspase-8 activity. CARD9 is suppressed during Salmonella enterica serovar Typhimurium infection, facilitating increased IL-1beta production. CARD9 is, therefore, a central signalling hub that coordinates a pathogen-specific host inflammatory response. PMID- 27670880 TI - Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole pyrrolidine derivatives and their biological applications. AB - A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4 dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text]. PMID- 27670881 TI - Indium triflate promoted one-pot multicomponent synthesis of structurally diverse 3-amino-imidazo[1,2-a]pyridines. AB - An efficient, mild, and expeditious synthetic protocol has been developed for the synthesis of structurally diverse 3-amino-imidazo[1,2-a]pyridines, involving a three-component, one-pot cyclocondensation reaction of 2-aminobenzothiazole/2 aminoazines, ethyl isocyanoacetate/tert-butyl isocyanides, and pyrazole-3(4) carbaldehyde/substituted aromatic carbonyl compounds in 45 min. using In(OTf)[Formula: see text] as a catalyst in toluene. Mild reaction conditions, high atom economy, operational simplicity, short reaction time, and structural diversity with high product conversion are among the advantages of the present synthetic protocol. PMID- 27670882 TI - Probiotic legacy effects on gut microbial assembly in tilapia larvae. AB - The exposure of fish to environmental free-living microbes and its effect on early colonization in the gut have been studied in recent years. However, little is known regarding how the host and environment interact to shape gut communities during early life. Here, we tested whether the early microbial exposure of tilapia larvae affects the gut microbiota at later life stages. The experimental period was divided into three stages: axenic, probiotic and active suspension. Axenic tilapia larvae were reared either under conventional conditions (active suspension systems) or exposed to a single strain probiotic (Bacillus subtilis) added to the water. Microbial characterization by Illumina HiSeq sequencing of 16S rRNA gene amplicons showed the presence of B. subtilis in the gut during the seven days of probiotic application. Although B. subtilis was no longer detected in the guts of fish exposed to the probiotic after day 7, gut microbiota of the exposed tilapia larvae remained significantly different from that of the control treatment. Compared with the control, fish gut microbiota under probiotic treatment was less affected by spatial differences resulting from tank replication, suggesting that the early probiotic contact contributed to the subsequent observation of low inter-individual variation. PMID- 27670883 TI - Tailoring Nucleation at Two Interfaces Enables Single Crystalline NiO Nanowires via Vapor-Liquid-Solid Route. AB - Here we show a rational strategy to fabricate single crystalline NiO nanowires via a vapor-liquid-solid (VLS) route, which essentially allows us to tailor the diameter and the spatial position. Our strategy is based on the suppression of the nucleation at vapor-solid (VS) interface, which promotes nucleation only at the liquid-solid (LS) interface. Manipulating both the supplied material fluxes (oxygen and metal) and the growth temperature enables enhancement of the nucleation only at the LS interface. Furthermore, this strategy allows us to reduce the growth temperature of single crystalline NiO nanowires down to 550 degrees C, which is the lowest growth temperature so far reported. PMID- 27670884 TI - 53BP1 ablation rescues genomic instability in mice expressing 'RING-less' BRCA1. AB - BRCA1 mutations strongly predispose affected individuals to breast and ovarian cancer, but the mechanism by which BRCA1 acts as a tumor suppressor is not fully understood. Homozygous deletion of exon 2 of the mouse Brca1 gene normally causes embryonic lethality, but we show that exon 2-deleted alleles of Brca1 are expressed as a mutant isoform that lacks the N-terminal RING domain. This "RING less" BRCA1 protein is stable and efficiently recruited to the sites of DNA damage. Surprisingly, robust RAD51 foci form in cells expressing RING-less BRCA1 in response to DNA damage, but the cells nonetheless display the substantial genomic instability. Genomic instability can be rescued by the deletion of Trp53bp1, which encodes the DNA damage response factor 53BP1, and mice expressing RING-less BRCA1 do not show an increased susceptibility to tumors in the absence of 53BP1. Genomic instability in cells expressing RING-less BRCA1 correlates with the loss of BARD1 and a defect in restart of replication forks after hydroxyurea treatment, suggesting a role of BRCA1-BARD1 in genomic integrity that is independent of RAD51 loading. PMID- 27670885 TI - Identification of PPM1D as an essential Ulk1 phosphatase for genotoxic stress induced autophagy. AB - Autophagy is an evolutionary conserved process that degrades subcellular constituents. Unlike starvation-induced autophagy, the molecular mechanism of genotoxic stress-induced autophagy has not yet been fully elucidated. In this study, we analyze the molecular mechanism of genotoxic stress-induced autophagy and identify an essential role of dephosphorylation of the Unc51-like kinase 1 (Ulk1) at Ser637, which is catalyzed by the protein phosphatase 1D magnesium dependent delta isoform (PPM1D). We show that after exposure to genotoxic stress, PPM1D interacts with and dephosphorylates Ulk1 at Ser637 in a p53-dependent manner. The PPM1D-dependent Ulk1 dephosphorylation triggers Ulk1 puncta formation and induces autophagy. This happens not only in mouse embryonic fibroblasts but also in primary thymocytes, where the genetic ablation of PPM1D reduces the dephosphorylation of Ulk1 at Ser637, inhibits autophagy, and accelerates apoptosis induced by X-ray irradiation. This acceleration of apoptosis is caused mainly by the inability of the autophagic machinery to degrade the proapoptotic molecule Noxa. These findings indicate that the PPM1D-Ulk1 axis plays a pivotal role in genotoxic stress-induced autophagy. PMID- 27670886 TI - Application of ligninolytic potentials of a white-rot fungus Ganoderma lucidum for degradation of lindane. AB - Lindane, a broad-spectrum organochlorine pesticide, has caused a widespread environmental contamination along with other pesticides due to wrong agricultural practices. The high efficiency, sustainability and eco-friendly nature of the bioremediation process provide an edge over traditional physico-chemical remediation for managing pesticide pollution. In the present study, lindane degradation was studied by using a white-rot fungus, Ganoderma lucidum GL-2 strain, grown on rice bran substrate for ligninolytic enzyme induction at 30 degrees C and pH 5.6 after incorporation of 4 and 40 ppm lindane in liquid as well as solid-state fermentation. The estimation of lindane residue was carried out by gas chromatography coupled to mass spectrometry (GC-MS) in the selected ion monitoring mode. In liquid-state fermentation, 100.13 U/ml laccase, 50.96 U/ml manganese peroxidase and 17.43 U/ml lignin peroxidase enzymes were obtained with a maximum of 75.50 % lindane degradation on the 28th day of incubation period, whereas under the solid-state fermentation system, 156.82 U/g laccase, 80.11 U/g manganese peroxidase and 18.61 U/g lignin peroxidase enzyme activities with 37.50 % lindane degradation were obtained. The lindane incorporation was inhibitory to the production of ligninolytic enzymes and its own degradation but was stimulatory for extracellular protein production. The dialysed crude enzyme extracts of ligninolytic enzymes were though efficient in lindane degradation during in vitro studies, but their efficiencies tend to decrease with an increase in the incubation period. Hence, lindane-degrading capabilities of G. lucidum GL 2 strain make it a potential candidate for managing lindane bioremediation at contaminated sites. PMID- 27670887 TI - The impact of seasonal variation on organochlorine pesticide residues in buffalo and cow milk of selected dairy farms from Faisalabad region. AB - Two hundred milk samples from 20 randomly selected dairy farms were screened for the incidence of organochlorine pesticide residues to evaluate the safety of milk in Faisalabad region. The results revealed that overall buffalo milk samples in winter (85 %) and in summer (78 %) were more contaminated as compared to cow milk samples 83 and 75 % in respective seasons. The residues of cyhalothrin were found only in summer season in milk of both species. Permethrin residues were detected at higher levels than perfinofos while DDT and methamedophos were found undetectable. The mean levels of permethrin were 0.042 and 0.033 mg kg-1in buffalo milk samples and 0.045 and 0.043 mg kg-1 in cow milk in winter and summer season, respectively. Perfinofos residues were found to be the least contaminated pesticides with mean values of 0.0006 and 0.0013 mg kg-1, respectively in winter season, and 0.004 and 0.0025 mg kg-1 in summer season. All analysed pesticide residues in milk samples in both seasons were below the maximum residual limit (MRL) values as described by European Union (EU) but milk samples contaminated with alpha, beta-endosulfan and endosulphate exceeded their respective Food and Agriculture Organization's (FAO) established MRLs both in winter and summer. PMID- 27670888 TI - Temporal variation in methane emissions in a shallow lake at a southern mid latitude during high and low rainfall periods. AB - The global methane (CH4) emission of lakes is estimated at between 6 and 16 % of total natural CH4 emissions. However, these values have a high uncertainty due to the wide variety of lakes with important differences in their morphological, biological, and physicochemical parameters and the relatively scarse data from southern mid-latitude lakes. For these reasons, we studied CH4 fluxes and CH4 dissolved in water in a typical shallow lake in the Pampean Wetland, Argentina, during four periods of consecutive years (April 2011-March 2015) preceded by different rainfall conditions. Other water physicochemical parameters were measured and meteorological data were reported. We identified three different states of the lake throughout the study as the result of the irregular alternation between high and low rainfall periods, with similar water temperature values but with important variations in dissolved oxygen, chemical oxygen demand, water turbidity, electric conductivity, and water level. As a consequence, marked seasonal and interannual variations occurred in CH4 dissolved in water and CH4 fluxes from the lake. These temporal variations were best reflected by water temperature and depth of the Secchi disk, as a water turbidity estimation, which had a significant double correlation with CH4 dissolved in water. The mean CH4 fluxes values were 0.22 and 4.09 mg/m2/h for periods with low and high water turbidity, respectively. This work suggests that water temperature and turbidity measurements could serve as indicator parameters of the state of the lake and, therefore, of its behavior as either a CH4 source or sink. PMID- 27670889 TI - The contribution of cluster and discriminant analysis to the classification of complex aquifer systems. AB - This paper presents an innovated method for the discrimination of groundwater samples in common groups representing the hydrogeological units from where they have been pumped. This method proved very efficient even in areas with complex hydrogeological regimes. The proposed method requires chemical analyses of water samples only for major ions, meaning that it is applicable to most of cases worldwide. Another benefit of the method is that it gives a further insight of the aquifer hydrogeochemistry as it provides the ions that are responsible for the discrimination of the group. The procedure begins with cluster analysis of the dataset in order to classify the samples in the corresponding hydrogeological unit. The feasibility of the method is proven from the fact that the samples of volcanic origin were separated into two different clusters, namely the lava units and the pyroclastic-ignimbritic aquifer. The second step is the discriminant analysis of the data which provides the functions that distinguish the groups from each other and the most significant variables that define the hydrochemical composition of the aquifer. The whole procedure was highly successful as the 94.7 % of the samples were classified to the correct aquifer system. Finally, the resulted functions can be safely used to categorize samples of either unknown or doubtful origin improving thus the quality and the size of existing hydrochemical databases. PMID- 27670890 TI - Radiosensitivity of Colon and Rectal Lung Oligometastasis Treated With Stereotactic Ablative Radiotherapy. AB - INTRODUCTION: Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. MATERIAL AND METHODS: This is a retrospective study including patients who presented with lung oligometastasis from CRC treated with SABR from September 2007 to November 2014. RESULTS: We identified 53 oligometastatic patients with 87 lung lesions. The median prescription dose was 60 Gy in 3 fractions (median biological effective dose of 180 Gy). The median follow up was 33 months. The 1- and 2-year local control, metastasis-free survival, and overall survival were 79.8% and 78.2%, 29.2% and 16.2%, and 83.8% and 69.3%, respectively. On multivariate analysis, rectal primary site (P = .001) and > 2 metastases (P = .02) were significantly associated with a lower local control rate. Rectal lesions were associated with higher radiation dose (169.3 Gy vs. 153.3 Gy; P = .01) and higher rate of KRAS mutations (73.3% vs. 40.4%; P = .02). KRAS mutation did not predict for local control, but predicted for a 1-year metastasis-free survival detriment (0% vs. 37.5%; P = .04), when compared with KRAS wild-type. On multivariate analysis, there is an overall survival detriment associated with gross tumor volume >= 3266 mm3 (P = .03) and > 2 metastases (P = .04). CONCLUSION: In CRC, oligometastatic lung lesions treated with SABR had a worse outcome in patients presenting with a rectal primary, > 2 metastases, or treated with a larger gross tumor volume. More aggressive treatment may be considered in this subset of patients to improve outcome. PMID- 27670891 TI - Exploring the Prognostic Role of Microsatellite Instability in Patients With Stage II Colorectal Cancer: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Many studies have disclosed the prognostic effect of microsatellite instability (MSI) and/or loss of mismatch repair proteins in colorectal cancer. Nevertheless, little evidence supports their role in the decision-making of adjuvant therapy for patients with stage II disease. MATERIALS AND METHODS: The aim of this systematic review was to evaluate the prognostic and/or predictive role of MSI status in patients with stage II colorectal cancer on disease-free survival and overall survival. MEDLINE, EMBASE, and Cochrane libraries were searched to identify eligible studies. RESULTS: Only 2 of 389 articles identified fulfilled the eligibility criteria. In both treated and untreated patients, high level MSI improved disease-free survival compared with low-level MSI, suggesting a prognostic role but not supporting the hypothesis of a predictive effect of MSI. CONCLUSIONS: Further studies are needed to explore the predictive role of MSI/mismatch repair proteins, because available data do not allow definitive conclusions. PMID- 27670892 TI - Regorafenib Versus Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: A Retrospective Comparison. AB - BACKGROUND: Regorafenib and trifluridine/tipiracil (TAS-102) both prolong survival for patients with refractory metastatic colorectal cancer. However, it is unclear which drug should be administered first. MATERIALS AND METHODS: We retrospectively evaluated the data from patients who had received regorafenib or TAS-102 at 2 institutions from May 2013 to March 2015. The inclusion criteria were disease refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, anti-vascular endothelial growth factor antibodies, and anti epidermal growth factor receptor (EGFR) antibodies (if KRAS exon 2 wild-type), and no previous treatment with regorafenib or TAS-102. RESULTS: A total of 146 and 54 patients received regorafenib and TAS-102, respectively. The baseline characteristics were similar between the 2 groups, except for a history of irinotecan and anti-EGFR therapy and high alkaline phosphatase levels. The median progression-free survival and overall survival were 2.1 months and 6.7 months, respectively, with regorafenib and 2.1 months and 6.5 months, respectively, with TAS-102 (progression-free survival hazard ratio 1.20, P = .27; overall survival hazard ratio, 1.01, P = .97). The analysis of overall survival for patients after the approval of TAS-102 in Japan was similar to the overall survival for the entire population. The frequency of hand-foot syndrome and increased aspartate aminotransferase, alanine aminotransferase, and bilirubin levels was higher and the frequency of neutropenia, leukopenia, anemia, nausea, and febrile neutropenia was lower with regorafenib than with TAS-102. No remarkable differences were found in the efficacy and safety of TAS-102 between patients with and without previous regorafenib and vice versa. CONCLUSION: Regorafenib and TAS-102 had similar efficacy but resulted in different toxicities, which could guide the agent choice. PMID- 27670893 TI - Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection. AB - BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. MATERIALS AND METHODS: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan Meier estimates. RESULTS: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. CONCLUSIONS: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection. PMID- 27670894 TI - Population-Based Patterns and Factors Associated With Underuse of Palliative Systemic Therapy in Elderly Patients With Metastatic Colon Cancer. AB - BACKGROUND: We compared the patterns and factors associated with chemotherapy and bevacizumab use in elderly versus young patients with metastatic colon cancer (mCC) and determined the effect of systemic therapy on overall survival (OS) according to age. MATERIALS AND METHODS: Patients diagnosed with mCC from 2009 to 2010 in British Columbia, Canada were reviewed and categorized as elderly patients (age >= 70 years) and young patients (age < 70 years). Cox regression models adjusted for age and confounders were used to determine the effect of systemic therapy on OS. RESULTS: We identified 1013 patients with a median age of 67 years. Of the 1013 patients, 42% were elderly and 58% were young; 57% were men; and 66% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Fewer elderly patients were offered systemic therapy compared with young patients (48% vs. 77%; P < .001). Among those treated, elderly patients were less likely than young patients to receive combination chemotherapy (47% vs. 81%; P < .0001) and bevacizumab (19% vs. 47%; P < .0001). The most common reasons for no treatment were similar for the elderly and young patients: patient choice, poor ECOG PS, and significant comorbidities. Advanced age alone was also cited as a reason for elderly but not for young patients (7% vs. 0%). When treated, the risk of adverse events and treatment interruptions was comparable between age groups. The receipt of systemic therapy was associated with improved OS in both elderly (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.37-0.56; P < .0001) and young (HR, 0.43; 95% CI, 0.35-0.53; P < .0001) patients, regardless of age (interaction P > .05). CONCLUSION: In carefully selected elderly patients, the outcomes from systemic therapy were comparable to those for young patients. Thus, age alone should not be a barrier to treatment of mCC. PMID- 27670895 TI - Peritoneal Carcinomatosis in Colorectal Cancers - Management Perspective Needs a Change. AB - BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancers (CRC) either at initial presentation or at subsequent recurrence presents a significant treatment challenge. The aim of our study was to find its incidence and analyze outcomes of patients with PC from CRC origin managed by different treatment modalities. PATIENTS AND METHODS: A retrospective analysis of patients, from August 2013 to July 2014, presenting with metastatic peritoneal disease from CRC with or without metastasis to other sites was performed. PC was classified as limited (peritoneal carcinomatosis index [PCI] < 10) and widespread (PCI > 10). RESULTS: This study included 70 patients; 45 patients had peritoneum as the only site of metastasis and the remaining 25 visceral metastasis with peritoneum. Resections were performed in 23 patients (19 underwent R0 resection and 4 were R+). All patients received systemic chemotherapy (FOLFOX [Oxaliplatin with fluorouracil and folinic acid]/CAPOX [oxaliplatin and capecitabine]). At a median follow-up of 11 months, the median OS was 14 months. Patients with PCI < 10 had significantly better survival (median not reached) as compared with those with PCI > 10 (15 months). Patients undergoing R0 resection had better survival (24 months) versus those with R+ resection (16 months). The survival of patients receiving only systemic chemotherapy was 11 months. CONCLUSION: The incidence of peritoneal metastasis in CRC is about 10%. A select group of patients who have low PCI who undergo R0 resection of only the diseased portion, without entire peritonectomy, still do well. Where facilities for hyperthermic intraperitoneal chemotherapy are not available, cytoreduction followed by systemic chemotherapy should be considered. The added role of hyperthermic intraperitoneal chemotherapy in this subgroup needs to be evaluated. PMID- 27670896 TI - Anthrax lethal toxin co-complexes are stabilized by contacts between adjacent lethal factors. PMID- 27670897 TI - Structure of anthrax lethal toxin prepore complex suggests a pathway for efficient cell entry. AB - Anthrax toxin comprises three soluble proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA must be cleaved by host proteases before it oligomerizes and forms a prepore, to which LF and EF bind. After endocytosis of this tripartite complex, the prepore transforms into a narrow transmembrane pore that delivers unfolded LF and EF into the host cytosol. Here, we find that translocation of multiple 90-kD LF molecules is rapid and efficient. To probe the molecular basis of this translocation, we calculated a three-dimensional map of the fully loaded (PA63)7-(LF)3 prepore complex by cryo-electron microscopy (cryo EM). The map shows three LFs bound in a similar way to one another, via their N terminal domains, to the surface of the PA heptamer. The model also reveals contacts between the N- and C-terminal domains of adjacent LF molecules. We propose that this molecular arrangement plays an important role in the maintenance of translocation efficiency through the narrow PA pore. PMID- 27670898 TI - Soluble adenylyl cyclase is essential for proper lysosomal acidification. AB - Lysosomes, the degradative organelles of the endocytic and autophagic pathways, function at an acidic pH. Lysosomes are acidified by the proton-pumping vacuolar ATPase (V-ATPase), but the molecular processes that set the organelle's pH are not completely understood. In particular, pH-sensitive signaling enzymes that can regulate lysosomal acidification in steady-state physiological conditions have yet to be identified. Soluble adenylyl cyclase (sAC) is a widely expressed source of cAMP that serves as a physiological pH sensor in cells. For example, in proton secreting epithelial cells, sAC is responsible for pH-dependent translocation of V-ATPase to the luminal surface. Here we show genetically and pharmacologically that sAC is also essential for lysosomal acidification. In the absence of sAC, V ATPase does not properly localize to lysosomes, lysosomes fail to fully acidify, lysosomal degradative capacity is diminished, and autophagolysosomes accumulate. PMID- 27670900 TI - Correction: Specific contributions of the four voltage-sensing domains in L-type calcium channels to gating and modulation. PMID- 27670901 TI - Introduction: Early adversity and brain development. PMID- 27670899 TI - Simultaneous imaging of local calcium and single sarcomere length in rat neonatal cardiomyocytes using yellow Cameleon-Nano140. AB - In cardiac muscle, contraction is triggered by sarcolemmal depolarization, resulting in an intracellular Ca(2+) transient, binding of Ca(2+) to troponin, and subsequent cross-bridge formation (excitation-contraction [EC] coupling). Here, we develop a novel experimental system for simultaneous nano-imaging of intracellular Ca(2+) dynamics and single sarcomere length (SL) in rat neonatal cardiomyocytes. We achieve this by expressing a fluorescence resonance energy transfer (FRET)-based Ca(2+) sensor yellow Cameleon-Nano (YC-Nano) fused to alpha actinin in order to localize to the Z disks. We find that, among four different YC-Nanos, alpha-actinin-YC-Nano140 is best suited for high-precision analysis of EC coupling and alpha-actinin-YC-Nano140 enables quantitative analyses of intracellular calcium transients and sarcomere dynamics at low and high temperatures, during spontaneous beating and with electrical stimulation. We use this tool to show that calcium transients are synchronized along the length of a myofibril. However, the averaging of SL along myofibrils causes a marked underestimate (~50%) of the magnitude of displacement because of the different timing of individual SL changes, regardless of the absence or presence of positive inotropy (via beta-adrenergic stimulation or enhanced actomyosin interaction). Finally, we find that beta-adrenergic stimulation with 50 nM isoproterenol accelerated Ca(2+) dynamics, in association with an approximately twofold increase in sarcomere lengthening velocity. We conclude that our experimental system has a broad range of potential applications for the unveiling molecular mechanisms of EC coupling in cardiomyocytes at the single sarcomere level. PMID- 27670902 TI - Functional synchrony and stimulus selectivity of visual cortical units: Comparison between cats and mice. AB - In spite of the fact that the functional organization of primary visual cortices (V1) differs across species, the dynamic of orientation selectivity is highly structured within neuronal populations. In fact, neurons functionally connect each other in an organized Hebbian process, wherein their wiring and firing are intimately related. Moreover, neuronal ensembles have been suggested to be strongly implicated in sensory processing. Within these ensembles, neurons may be sharply or broadly tuned in relation to the stimulus. Therefore, it is important to determine the relationship between the response selectivity of neurons and their functional connectivity pattern across species. In the present investigation, we sought to compare the stimulus-evoked functional connectivity between the broadly tuned and the sharply tuned neurons in two species exhibiting different cortical organization for orientation selectivity: cats (columnar organized) and mice (salt-and-pepper organization). In addition, we examined the distribution of connectivity weights within cell-assemblies in the visual cortex during visual adaptation. First, we report that the sharply tuned neurons exhibited higher synchrony index than the broadly tuned cells in the cat visual cortex. On the contrary, in mice, the broadly tuned cells displayed higher connectivity index. Second, a significant correlation was found between the connectivity strength and the difference of preferred orientations of neurons for both species. Finally, we observed a systematic adjustment of the connectivity weights within neuronal ensembles in mouse primary visual cortex similarly to the cat V1. PMID- 27670903 TI - Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy. AB - Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms. In one set of experiments, rats received RIN treatment prior to pilocarpine injection. In a second set of experiments, rats received RIN treatment following the onset of stage 3 seizures. Pretreatment and posttreatment with RIN effectively reduced the seizure severity in the acute phase of TLE. Furthermore, RIN protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated spontaneous epileptiform discharge of mEC layer II neurons in SE-experienced rats. Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INap and NMDA receptor current inhibition. PMID- 27670905 TI - Independently ambulant, community-dwelling stroke survivors have reduced cardiorespiratory fitness, mobility and knee strength compared to an age- and gender-matched cohort. AB - BACKGROUND: Most exercise interventions for stroke survivors are designed for those who have substantial motor and functional disabilities. There remains a group of well-recovered stroke survivors who have yet to be investigated in terms of their physical capacity and fitness levels. OBJECTIVE: To assess and compare the physical capacities of independently ambulant, community-dwelling stroke survivors to age- and gender-matched comparison participants. METHODS: Data were obtained from 17 stroke survivors participating in the How FITSS? Trial, all with functional ambulatory category of >=4 and a self-selected walking speed >=0.8 m s 1. An additional 17 healthy control participants were recruited. Cardiorespiratory fitness (CRF) was measured using oxygen consumption (VO2peak), and additional measures of walking speed (m s-1), leg strength and body composition were also assessed. Differences between groups were assessed by matched pairs t-tests. Effect sizes were calculated using Cohen's d. RESULTS: There were no significant differences in age, BMI, muscle mass or body fat between groups (p > 0.05). Peak VO2 was lower in the stroke group for the shuttle walk test (p = 0.037) and progressive cycle test (p = 0.019), as were all CRF test performance measures (p < 0.05). Stroke survivors walked significantly (p < 0.001) slower at both self-selected and fast speeds. Effect sizes of group differences for all leg strength variables were medium to large, with peak torque lower in the stroke group for all trials. CONCLUSIONS: Despite being independently ambulant and community dwelling, the CRF, walking speed and leg strength of this group were reduced compared to non-stroke comparison participants. These patients may benefit from undertaking targeted exercise programmes. PMID- 27670904 TI - Cooling During Exercise: An Overlooked Strategy for Enhancing Endurance Performance in the Heat. AB - It is well established that endurance performance is negatively affected by environmental heat stress due to a complex interaction of physical, physiological and psychological alterations. Numerous scientific investigations have attempted to improve performance in the heat with pre-cooling (cooling prior to an exercise test), and as such this has become a well-established ergogenic practice for endurance athletes. However, the use of mid-cooling (cooling during an exercise test) has received considerably less research attention in comparison, despite recent evidence to suggest that the advantage gained from mid-cooling may outweigh that of pre-cooling. A range of mid-cooling strategies are beneficial for endurance performance in the heat, including the ingestion of cold fluids and ice slurry, both with and without menthol, as well as cooling of the neck and face region via a cooling collar or water poured on the head and face. The combination of pre-cooling and mid-cooling has also been effective, but few comparisons exist between the timing and type of such interventions. Therefore, athletes should experiment with a range of suitable mid-cooling strategies for their event during mock competition scenarios, with the aim to determine their individual tolerable limits and performance benefits. Based on current evidence, the effect of mid-cooling on core temperature appears largely irrelevant to any subsequent performance improvements, while cardiovascular, skin temperature, central nervous system function and psychophysiological factors are likely involved. Research is lacking on elite athletes, and as such it is currently unclear how this population may benefit from mid-cooling. PMID- 27670906 TI - Early diagnosis of dengue disease severity in a resource-limited Asian country. AB - BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. PMID- 27670907 TI - The International Incidence of Traumatic Brain Injury: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Understanding the epidemiology of traumatic brain injury (TBI) is essential to shape public health policy, implement prevention strategies, and justify allocation of resources toward research, education, and rehabilitation in TBI. There is not, to our knowledge, a systematic review of population-based studies addressing the epidemiology of TBI that includes all subtypes. We performed a comprehensive systematic review and meta-analysis of the worldwide incidence of TBI. METHODS: A search was conducted on May 23, 2014, in Medline and EMBASE according to Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Abstracts were screened independently and in duplicate to identify original research. Study quality and ascertainment bias were assessed in duplicate using a previously published tool. Demographic data and incidence estimates from each study were recorded, along with stratification by age, gender, year of data collection, and severity. RESULTS: The search strategy yielded 4944 citations. Two hundred and sixteen articles met criteria for full text review; 144 were excluded. Hand searching resulted in ten additional articles. Eighty-two studies met all eligibility criteria. The pooled annual incidence proportion for all ages was 295 per 100,000 (95% confidence interval: 274-317). The pooled incidence rate for all ages was 349 (95% confidence interval: 96.2-1266) per 100,000 person-years. Incidence proportion and incidence rate were examined to see if associated with age, sex, country, or severity. CONCLUSIONS: We conclude that most TBIs are mild and most TBIs occur in males among the adult population. The incidence of TBI varies widely by ages and between countries. Despite being an important medical, economic, and social problem, the global epidemiology of TBI is still not well-characterized in the current literature. Understanding the incidence of TBI, particularly mild TBI, remains challenging because of nonstandardized reporting among neuroepidemiological studies. PMID- 27670908 TI - Relationship between literacy skills and self-reported health in the Nordic countries. AB - AIMS: This study investigated the association between literacy skills and self reported health among Danish ( n = 7284), Finnish ( n = 5454), Norwegian ( n = 4942) and Swedish ( n = 4555) participants aged 16-65 years. METHODS: Logistic regression models were used to assess the association between literacy skills and self-reported health after adjusting for sex, age and educational level. RESULTS: Nordic participants aged 16-65 years with literacy skills at the lowest level reported sub-optimal health more often (28-37%) than those with literacy skills at the highest level (7-9%). After adjusting for sex, age and educational level, the likelihood of reporting sub-optimal health was 1.99-3.24 times as high for those with literacy skills at the lowest level as for those with literacy skills at the highest level. CONCLUSIONS: These results suggest that poor literacy skills increase the likelihood of experiencing poor health in the Nordic countries, even after controlling for educational level. PMID- 27670909 TI - Tracking a female foetus: Preventing gender imbalance in India. PMID- 27670910 TI - Visual food stimulus changes resting oscillatory brain activities related to appetitive motive. AB - BACKGROUND: Changes of resting brain activities after visual food stimulation might affect the feeling of pleasure in eating food in daily life and spontaneous appetitive motives. We used magnetoencephalography (MEG) to identify brain areas related to the activity changes. METHODS: Fifteen healthy, right-handed males [age, 25.4 +/- 5.5 years; body mass index, 22.5 +/- 2.7 kg/m2 (mean +/- SD)] were enrolled. They were asked to watch food or mosaic pictures for 5 min and to close their eyes for 3 min before and after the picture presentation without thinking of anything. Resting brain activities were recorded during two eye-closed sessions. The feeling of pleasure in eating food in daily life and appetitive motives in the study setting were assessed by visual analogue scale (VAS) scores. RESULTS: The gamma-band power of resting oscillatory brain activities was decreased after the food picture presentation in the right insula [Brodmann's area (BA) 13], the left orbitofrontal cortex (OFC) (BA11), and the left frontal pole (BA10). Significant reductions of the alpha-band power were observed in the dorsolateral prefrontal cortex (DLPFC) (BA46). Particularly, the feeling of pleasure in eating food was positively correlated with the power decrease in the insula and negatively with that in the DLPFC. The changes in appetitive motives were associated with the power decrease in the frontal pole. CONCLUSIONS: These findings suggest automatic brain mechanics whereby changes of the resting brain activity might be associated with positive feeling in dietary life and have an impact on the irresistible appetitive motives through emotional and cognitive brain functions. PMID- 27670911 TI - Erratum to: Prescription reporting with immediate medication utilization mapping (PRIMUM): development of an alert to improve narcotic prescribing. PMID- 27670912 TI - Fatal respiratory disease due to a homozygous intronic ABCA3 mutation: a case report. AB - BACKGROUND: Pulmonary surfactant is a complex mixture of lipids and proteins. Mutations in surfactant protein-C, surfactant protein-D, and adenosine triphosphate-binding cassette subfamily A member 3 have been related to surfactant dysfunction and neonatal respiratory failure in full-term babies. Adenosine triphosphate-binding cassette subfamily A member 3 facilitates the transfer of lipids to lamellar bodies. We report the case of patient with a homozygous intronic ABCA3 mutation. CASE PRESENTATION: We describe a newborn full term Colombian baby boy who was the son of non-consanguineous parents of mixed race ancestry (Mestizo), who was delivered with severe respiratory depression. Invasive treatment was unsuccessful and diagnosis was uncertain. Exons 4 and 5 of the SP-C gene showed heterozygous Thr138Asn polymorphism and homozygous Asn186Asn polymorphism respectively. At intron 25 at position -98 from exon 26 a homozygous C>T transition mutation was detected in ABCA3 gene. CONCLUSIONS: The clinical presentation and the histopathological findings of this case are consistent with a case of neonatal respiratory failure due to surfactant deficiency. Analysis of the five coding SP-C exons does not support surfactant deficiency. An analysis of the mutation IVS25-98 T was performed and a homozygous mutation responsible for our case's neonatal respiratory failure was detected. The findings suggest an autosomic recessive pattern of inheritance. Genetic counseling was provided and the relatives are now informed of the recurrence risks and treatment options. PMID- 27670913 TI - Reply. PMID- 27670914 TI - Impact of type of full-field digital image on mammographic density assessment and breast cancer risk estimation: a case-control study. AB - BACKGROUND: Full-field digital mammography, which is gradually being introduced in most clinical and screening settings, produces two types of images: raw and processed. However, the extent to which mammographic density measurements, and their ability to predict breast cancer risk, vary according to type of image is not fully known. METHODS: We compared the performance of the semi-automated Cumulus method on digital raw, "analogue-like" raw and processed images, and the performance of a recently developed method - Laboratory for Breast Radiodensity Assessment (LIBRA) - on digital raw and processed images, in a case-control study (414 patients (cases) and 684 controls) by evaluating the extent to which their measurements were associated with breast cancer risk factors, and by comparing their ability to predict breast cancer risk. RESULTS: Valid Cumulus and LIBRA measurements were obtained from all available images, but the resulting distributions differed according to the method and type of image used. Both Cumulus and LIBRA percent density were inversely associated with age, body mass index (BMI), parity and postmenopausal status, regardless of type of image used. Cumulus percent density was strongly associated with breast cancer risk, but with the magnitude of the association slightly stronger for processed (risk increase per one SD increase in percent density (95 % CI): 1.55 (1.29, 1.85)) and "analogue-like" raw (1.52 (1.28, 1.80)) than for raw (1.35 (1.14, 1.60)) images. LIBRA percent density produced weaker associations with risk, albeit stronger for processed (1.32 (1.08, 1.61)) than raw images (1.17 (0.99, 1.37)). The percent density values yielded by the various density assessment/type of image combinations had similar ability to discriminate between patients and controls (area under the receiving operating curve values for percent density, age, BMI, parity and menopausal status combined ranged from 0.61 and 0.64). CONCLUSIONS: The findings showed that Cumulus can be used to measure density on all types of digital images. They also indicate that LIBRA may provide a valid fully automated alternative to the more labour-intensive Cumulus. However, the same digital image type and assessment method should be used when examining mammographic density across populations, or longitudinal changes in density within a single population. PMID- 27670915 TI - Early Postoperative Radiotherapy is Associated with Worse Functional Outcomes in Patients with Prostate Cancer. AB - PURPOSE: The effect of time between radical prostatectomy and radiation therapy on postoperative functional outcomes is still unclear in patients with surgically managed prostate cancer. We hypothesized that a shorter time between radical prostatectomy and radiotherapy might be associated with worse functional recovery rates after radical prostatectomy. MATERIALS AND METHODS: We retrospectively evaluated 2,190 patients treated with radical prostatectomy and stratified according to radiotherapy schedule (adjuvant radiotherapy, salvage radiotherapy, no radiotherapy). We examined recovery rates for erectile function and urinary function according to adjuvant radiotherapy, salvage radiotherapy and no radiotherapy, and according to time from surgery to radiotherapy. Cox regression analyses were used to evaluate the impact of these predictors on functional outcomes. RESULTS: Median followup was 48 months. The 3-year erectile function recovery rates were 35.0%, 29.0% and 11.6% in patients who received no radiotherapy, salvage radiotherapy and adjuvant radiotherapy, respectively (p <0.001), and differed significantly according to time to radiotherapy (11.7% vs 34.7% for less than 1 year vs 1 year or more, respectively, p <0.001). The 3-year urinary continence recovery rates were 70.7%, 59.0% and 42.2% in patients who received no radiotherapy, salvage radiotherapy and adjuvant radiotherapy, respectively (p <0.001), and differed according to time to radiotherapy (43.5% vs 62.7% for less than 1 year vs 1 year or more, respectively, p <0.001). Cox regression analyses confirmed the negative impact of early radiotherapy on recovery rates for erectile function and urinary continence. CONCLUSIONS: Time from radical prostatectomy to radiotherapy has an important role in the recovery of erectile function and urinary continence. Delayed radiotherapy is preferred to improve functional outcomes after surgery. PMID- 27670916 TI - Postoperative Nomogram for Relapse-Free Survival in Patients with High Grade Upper Tract Urothelial Carcinoma. AB - PURPOSE: We developed a prognostic nomogram for patients with high grade urothelial carcinoma of the upper urinary tract after extirpative surgery. MATERIALS AND METHODS: Clinical data were available for 2,926 patients diagnosed with high grade urothelial carcinoma of the upper urinary tract who underwent extirpative surgery. Cox proportional hazard regression models identified independent prognosticators of relapse in the development cohort (838). A backward step-down selection process was applied to achieve the most informative nomogram with the least number of variables. The L2-regularized logistic regression was applied to generate the novel nomogram. Harrell's concordance indices were calculated to estimate the discriminative accuracy of the model. Internal validation processes were performed using bootstrapping, random sampling, tenfold cross-validation, LOOCV, Brier score, information score and F1 score. External validation was performed on an external cohort (2,088). Decision tree analysis was used to develop a risk classification model. Kaplan-Meier curves were applied to estimate the relapse rate for each category. RESULTS: Overall 35.3% and 30.7% of patients experienced relapse in the development and external validation cohort. The final nomogram included age, pT stage, pN stage and architecture. It achieved a discriminative accuracy of 0.71 and 0.76, and the AUC was 0.78 and 0.77 in the development and external validation cohort, respectively. Rigorous testing showed constant results. The 5-year relapse-free survival rates were 88.6%, 68.1%, 40.2% and 12.5% for the patients with low risk, intermediate risk, high risk and very high risk disease, respectively. CONCLUSIONS: The current nomogram, consisting of only 4 variables, shows high prognostic accuracy and risk stratification for patients with high grade urothelial carcinoma of the upper urinary tract following extirpative surgery, thereby adding meaningful information for clinical decision making. PMID- 27670917 TI - Glycomyces lacisalsi sp. nov., an actinomycete isolated from a hypersaline habitat. AB - A novel actinomycete strain, designated XHU 5089T, was isolated from a hypersaline habitat in China. The strain was aerobic, Gram-stain-positive and the optimum NaCl concentration for growth was 1-3 % (w/v). Phylogenetic analysis based on the almost-complete 16S rRNA gene sequence of strain XHU 5089T showed that the organism was related most closely to Glycomyces albusTRM 49136T (97.7 % similarity). However, it had a relatively low mean DNA-DNA relatedness value with G. albusTRM 49136T (18.9+/-5.8 %). The whole-cell sugar pattern consisted of glucose and galactose. The predominant menaquinones were MK-10(H4) and MK-9(H4). The major fatty acids were anteiso-C15 : 0, iso-C16 : 0, iso-C16 : 1 and anteiso C17 : 0. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two unidentified glycolipids and two unknown phospholipids. The G+C content of the genomic DNA was 68.6 mol%. A novel species, Glycomyces lacisalsi sp. nov., is proposed, with XHU 5089T (=CCTCC AA 2015034T=KCTC 39688T) as the type strain. PMID- 27670919 TI - Airport door handles and the global spread of antimicrobial-resistant bacteria: a cross sectional study. PMID- 27670918 TI - Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia. AB - Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for, and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia. Now using the approach of in utero gene transfer we have discovered that Ulk4 plays a key modulatory role in corticogenesis. Knockdown of Ulk4 leads to significantly decreased cell proliferation in germinal zones and profound deficits in radial migration and neurite ramification. These abnormalities can be reversed successfully by Ulk4 gene supplementation. Ulk4 also regulated acetylation of alpha-tubulin, an important post-translational modification of microtubules. We conclude that Ulk4 plays an essential role in normal brain development and when defective, the risk of neurodevelopmental disorders such as schizophrenia is increased. PMID- 27670921 TI - Estimating bias in derived body mass index in the Maternity Experiences Survey. AB - INTRODUCTION: The objective of this study was to assess bias in the body mass index (BMI) measure in the Canadian Maternity Experiences Survey (MES) and possible implications of bias on the relationship between BMI and selected pregnancy outcomes. METHODS: We assessed BMI classification based on self reported versus measured values. We used a random sample of 6175 women from the MES, which derived BMI from self-reported height and weight, and a random sample of 259 women who had previously given birth from the Canadian Health Measures Survey (CHMS), which derived BMI from self-reported and measured height and weight. Two correction equations were applied to self-reported based BMI, and the impact of these corrections on associations between BMI and caesarean section, small-for-gestational age (SGA) and large-for-gestational age (LGA) births was studied. RESULTS: Overall, 86.9% of the CHMS subsample was classified into the same BMI category based on self-reported versus measured data. However, misclassification had a substantial effect on the proportion of women in underweight and obese BMI categories. For example, 14.5% versus 20.8% of women were classified as obese based on self-reported data versus measured data. Corrections improved estimates of obesity prevalence, but over- and underestimated other BMI categories. Corrections had nonsignificant effects on the associations between BMI and SGA, LGA, and caesarean section. CONCLUSION: While there was high concordance in BMI classification based on selfreported versus measured height and weight, bias in self-reported based measures may slightly over- or underestimate the risks associated with a particular BMI class. However, the general trend in associations is unaffected. PMID- 27670920 TI - How perceptions of community environment influence health behaviours: using the Analysis Grid for Environments Linked to Obesity Framework as a mechanism for exploration. AB - INTRODUCTION: Overweight and obesity are influenced by a complex interplay of individual and environmental factors that affect physical activity and healthy eating. Nevertheless, little has been reported on people's perceptions of those factors. Addressing this critical gap and community partner needs, this study explored how people perceived the influence of micro- and macroenvironmental factors on physical activity and healthy eating. METHODS: Community partners wanted the study results in a format that would be readily and easily used by local decision makers. We used photovoice to engage 35 community members across four municipalities in Alberta, Canada, and to share their narratives about their physical activity and healthy eating. A combination of inductive and deductive analysis categorized data by environmental level (micro vs. macro) and type (physical, political, economic, and sociocultural), guided by the Analysis Grid for Environments Linked to Obesity Framework. RESULTS: Participants conceptualized health-influencing factors more broadly than physical activity and healthy eating to include "community social health." Participants spoke most often about the influence of the microenvironment (n = 792 ANGELO Framework coding tallies) on their physical activity, healthy eating and community social health in comparison to the macroenvironment (n = 93). Photovoice results provided a visual narrative to community partners and decision makers about how people's ability to make healthy choices can be limited by macroenvironmental forces beyond their control. CONCLUSION: Focussing future research on macro- and microenvironmental influences and localized community social health can inform practice by providing strategies on how to implement healthy changes within communities, while ensuring that research and interventions echo diverse people's perceptions. PMID- 27670922 TI - Childhood overweight and obesity trends in Canada. AB - INTRODUCTION: Excess weight is a key risk factor for chronic disease, and the systematic collection, analysis and reporting of key trends are important to surveillance of overweight and obesity. METHODS: We used univariate analyses to calculate current prevalence estimates of excess weight among Canadian children and youth. RESULTS: Almost 1 in 7 children and youth is obese. Rates vary based on sociodemographic factors such as age, sex, socioeconomic status and place of residence. Overall, the rates of excess weight have been relatively stable over the past decade. CONCLUSION: Ongoing monitoring of childhood obesity will provide useful information to assist with sustained actions to promote healthy weights. PMID- 27670923 TI - Correction: Health behaviours associated with indoor tanning based on the 2012/13 Manitoba Youth Health Survey. AB - [This corrects the article http://www.phac-aspc.gc.ca/publicat/hpcdp-pspmc/36 8/ar-02-eng.php]. PMID- 27670924 TI - Disentangling the relative roles of resource acquisition and allocation on animal feed efficiency: insights from a dairy cow model. AB - BACKGROUND: Feed efficiency of farm animals has greatly improved through genetic selection for production. Today, we are faced with the limits of our ability to predict the effect of selection on feed efficiency, partly because the relative importance of the components of this complex phenotype changes across environments. Thus, we developed a dairy cow model that incorporates the dynamic interplay between life functions and evaluated its behaviour with a global sensitivity analysis on two definitions of feed efficiency. A key model feature is to consider feed efficiency as the result of two processes, acquisition and allocation of resources. Acquisition encapsulates intake and digestion, and allocation encapsulates partitioning rules between physiological functions. The model generates genetically-driven trajectories of energy acquisition and allocation, with four genetic-scaling parameters controlling these processes. Model sensitivity to these parameters was assessed with a complete factorial design. RESULTS: Acquisition and allocation had contrasting effects on feed efficiency (ratio between energy in milk and energy acquired from the environment). When measured over a lactation period, feed efficiency was increased by increasing allocation to lactation. However, at the lifetime level, efficiency was increased by decreasing allocation to growth and increasing lactation acquisition. While there is a strong linear increase in feed efficiency with more allocation to lactation within a lactation cycle, our results suggest that there is an optimal level of allocation to lactation beyond which increasing allocation to lactation negatively affects lifetime feed efficiency. CONCLUSIONS: We developed a model to predict lactation and lifetime feed efficiency and show that breaking-down feed conversion into acquisition and allocation, and introducing genetically-driven trajectories that control these mechanisms, permitted quantification of their relative roles on feed efficiency. The life stage at which feed efficiency is evaluated appears to be a key aspect for selection. In this model, body reserves are also a key component in the prediction of lifetime feed efficiency since they integrate the feedback of acquisition and allocation on survival and reproduction. This modelling approach provided new insights into the processes that underpin lifetime feed efficiency in dairy cows. PMID- 27670926 TI - Posttraumatic Hydrocephalus as a Confounding Influence on Brain Injury Rehabilitation: Incidence, Clinical Characteristics, and Outcomes. AB - OBJECTIVE: To describe incidence, clinical characteristics, complications, and outcomes in posttraumatic hydrocephalus (PTH) after traumatic brain injury (TBI) for patients treated in an inpatient rehabilitation program. DESIGN: Cohort study with retrospective comparative analysis. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: All patients admitted for TBI from 2009 to 2013 diagnosed with PTH (N=59), defined as ventriculomegaly, delayed clinical recovery discordant with injury severity, hydrocephalus symptoms, or positive lumbar puncture results. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary measures were incidence of PTH and patient and injury characteristics. Secondary measures included frequency and timing of ventriculoperitoneal (VP) shunt, related complications, emergence from and duration of posttraumatic amnesia (PTA), Rancho Los Amigos Scale (RLAS) score, and FIM score at rehabilitation admission and discharge. RESULTS: Of 701 patients with TBI admitted, 59 (8%) were diagnosed with PTH. Of these, the median age was 25 years, with 73% being men. At initial presentation, 52 (88%) did not follow commands. Fifty-two (90%) patients with PTH had a VP shunt placed. Median time from injury to shunt placement was 69 (range, 9-366) days. Seven (12%) patients with PTH experienced postsurgical seizure, 3 (6%) had shunt infection, and 7 (12%) had shunt malfunction. Thirty-six (61%) patients with PTH emerged from PTA during rehabilitation. Median total FIM score at rehabilitation admission was 20 (range, 18-76), and at discharge it was 43 (range, 18-118). Injury severity predicted outcome at rehabilitation admission, whereas shunt timing predicted outcome at rehabilitation discharge. CONCLUSIONS: Incidence of PTH was observed in 8% of patients with TBI in inpatient rehabilitation. Earlier shunting predicted improved outcome during rehabilitation. Future studies should prospectively examine clinical decision rules, type, and timing of intervention and the coeffectiveness of rehabilitation treatment on outcomes. PMID- 27670925 TI - Use of Mobile Device Accelerometry to Enhance Evaluation of Postural Instability in Parkinson Disease. AB - OBJECTIVE: To determine the accuracy of inertial measurement unit data from a mobile device using the mobile device relative to posturography to quantify postural stability in individuals with Parkinson disease (PD). DESIGN: Criterion standard. SETTING: Motor control laboratory at a clinic. PARTICIPANTS: A sample (N=28) of individuals with mild to moderate PD (n=14) and age-matched community dwelling individuals without PD (n=14) completed the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center of mass (COM) acceleration measures were compared between the mobile device and the NeuroCom force platform to determine the accuracy of mobile device measurements during performance of the Sensory Organization Test (SOT). Analyses examined test-retest reliability of both systems and sensitivity of (1) the equilibrium score from the SOT and (2) COM acceleration measures from the force platform and mobile device to quantify postural stability across populations. RESULTS: Metrics of COM acceleration from inertial measurement unit data and the NeuroCom force platform were significantly correlated across balance conditions and groups (Pearson r range, .35 to .97). The SOT equilibrium scores failed to discriminate individuals with and without PD. However, the multiplanar measures of COM acceleration from the mobile device exhibited good to excellent reliability across SOT conditions and were able to discriminate individuals with and without PD in conditions with the greatest balance demands. CONCLUSIONS: Metrics employing medial-lateral movement produce a more sensitive outcome than the equilibrium score in identifying postural instability associated with PD. Overall, the output from the mobile device provides an accurate and reliable method of rapidly quantifying balance in individuals with PD. The portable and affordable nature of a mobile device with the application makes it ideally suited to use biomechanical data to aid in clinical decision making. PMID- 27670928 TI - The performance of rigid scopes for tracheal intubation: a randomised, controlled trial in patients with a simulated difficult airway. AB - We compared the BonfilsTM and SensaScopeTM rigid fibreoptic scopes in 200 patients with a simulated difficult airway randomised to one of the two devices. A cervical collar inhibited neck movement and reduced mouth opening to a mean (SD) of 23 (3) mm. The primary outcome parameter was overall success of tracheal intubation; secondary outcomes included first-attempt success, intubation times, difficulty of intubation, fibreoptic view and side-effects. The mean (95% CI) overall success rate was 88 (80-94)% for the Bonfils and 89 (81-94)% for the SensaScope (p = 0.83). First-attempt intubation success rates were 63 (53-72)% for the Bonfils and 72 (62-81)% for the SensaScope (p = 0.17). Median (IQR [range]) intubation time was significantly shorter with the SensaScope (34 (20-84 [5-240]) s vs. 45 (25-134 [12-230]) s), and fibreoptic view was significantly better with the SensaScope (full view of the glottis in 79% with the SensaScope vs. 61% with the Bonfils). This might be explained by its steerable tip and the S formed shape, contributing to better manoeuvrability. There were no differences in the difficulty of intubation or side-effects. PMID- 27670927 TI - A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride. AB - A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl2) via inhalation at concentrations of 0 (air-control); 5, 10 and 20MUg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20MUg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants. PMID- 27670929 TI - Temperature-dependent photoluminescence emission and Raman scattering from Mo1-x W x S2 monolayers. AB - 2D transition metal dichalcogenide (TMD) alloys with tunable band gaps have recently gained wide interest due to their potential applications in future nanoelectronics and optoelectronics. Here, we report the temperature-dependent photoluminescence (PL) and Raman spectra of Mo1-x W x S2 monolayers with W composition x = 0, 0.29, 0.53, 0.66 and 1 in the temperature range 93-493 K. We observed a linear temperature dependence of PL emission energy and Raman frequency. The PL intensity is enhanced at high temperature (>393 K). The temperature coefficients are negative for both PL and Raman bands, which may result from anharmonicity, thermal expansion and composition disorder. PMID- 27670930 TI - Lottery for medical school admission. PMID- 27670931 TI - Expression of the insulinoma-associated 1 (insm1) gene in Xenopus laevis tadpole retina and brain. AB - The insulinoma-associated 1 (insm1) gene is involved in the differentiation of several neuronal and endoderm derived cell types. insm1 is expressed in the retina and brain of several vertebrates including Xenopus laevis. We report the detailed expression pattern of insm1 in the X. laevis tadpole retina and brain. X. laevis insm1 is expressed in most of the ciliary marginal zone of the mature retina and the optic tectum, dorsal pallium, hypothalamus and preoptic areas of the developing tadpole brain. Overall, insm1 is expressed in regions of the tadpole brain and retina harboring populations of progenitor cells. PMID- 27670934 TI - Cystic ovaries and ovarian neoplasia in the female dog - a systematic review. AB - Most common ovarian diseases appear to be cystic or ovarian tumours. These conditions may affect health, fertility or even the life of the animal. Literature related to ovarian cysts and neoplasia in dogs was assessed to summarize studies and case series on ovarian cysts and primary ovarian tumours in regard to epidemiologic, clinical and fertility aspects. Two research papers on histopathological examination of ovarian cysts could be identified. Seven research papers on ovarian tumours were also assessed, showing inconsistent results on the frequency of occurrence of different types of neoplasia. This might be due to different definitions of diseases and different diagnostic procedures. In conclusion, scarce research has been performed on ovarian diseases in the bitch in the last decades. Many publications are based on case reports. Most quality criteria of study methodology like blinding, randomization, sensitivity and specificity of test methods are not considered in papers on ovarian diseases. In the future, a multicentre data collection of cases could help to gather more data on the incidence, clinical relevance, treatment options and prognosis of ovarian diseases. PMID- 27670933 TI - Referral patterns of special needs patients at the Royal Dental Hospital of Melbourne, Victoria, Australia. AB - BACKGROUND: Special Needs Dentistry (SND) has been recognized as a dental specialty in Australia since 2003 but there have been no studies addressing the profile of patients for specialist care. The purpose of this study is to identify, via referrals received, the profile of patients and quality of referrals at the largest public SND unit in Victoria, Australia. METHODS: All referrals received over a 6-month period (1 January-30 June 2013) by the integrated SND unit (ISNU) were reviewed prior to allocation to the outpatient clinic (OP), domiciliary (DOM) or general anaesthetic (GA) services. RESULTS: Six hundred and eighty-eight referrals were received with the majority for the OP clinic (68.3%), followed by DOM (22.4%) and GA services (9.3%) (chi2 = 360.2, P < 0.001). A referral may have specified more than one special needs condition with the most common category being those who were medically compromised (81.7%). The reasons for referral included lack of compliance (27.2%), further management due to multiple medical conditions or GA services required (9.9%), or for multiple other reasons (62.9%). CONCLUSIONS: A diverse pattern of SND patients was referred to the ISNU with a majority of referrals having no specific referral reason cited, suggesting poor quality of referrals. PMID- 27670932 TI - Validity of using ad hoc methods to analyze secondary traits in case-control association studies. AB - Case-control association studies often collect from their subjects information on secondary phenotypes. Reusing the data and studying the association between genes and secondary phenotypes provide an attractive and cost-effective approach that can lead to discovery of new genetic associations. A number of approaches have been proposed, including simple and computationally efficient ad hoc methods that ignore ascertainment or stratify on case-control status. Justification for these approaches relies on the assumption of no covariates and the correct specification of the primary disease model as a logistic model. Both might not be true in practice, for example, in the presence of population stratification or the primary disease model following a probit model. In this paper, we investigate the validity of ad hoc methods in the presence of covariates and possible disease model misspecification. We show that in taking an ad hoc approach, it may be desirable to include covariates that affect the primary disease in the secondary phenotype model, even though these covariates are not necessarily associated with the secondary phenotype. We also show that when the disease is rare, ad hoc methods can lead to severely biased estimation and inference if the true disease model follows a probit model instead of a logistic model. Our results are justified theoretically and via simulations. Applied to real data analysis of genetic associations with cigarette smoking, ad hoc methods collectively identified as highly significant (P<10-5) single nucleotide polymorphisms from over 10 genes, genes that were identified in previous studies of smoking cessation. PMID- 27670935 TI - Determination of gestational time and prediction of parturition in dogs and cats: an update. AB - Accurate prediction of delivery date in canine and feline allows a better management of parturition, reducing the loss of neonates. This review evaluates the most common methods adopted to accurately predict the day of delivery: determination of ovulation and hormonal assays, first appearance of embryonic/foetal structures using ultrasound or radiography, echographic measurement of extra-foetal and foetal structures, or evaluation of foetal flux and heart rate. Determination of ovulation and hormonal assays at the time of breeding and close to pregnancy term is widely used to predict parturition in dogs (Concannon et al. American Journal of Veterinary Research 44, 1983, 1819; Hayer et al. Journal of Reproduction and Fertility, Suppl. 47, 1993, 93; Hase et al. Journal of Veterinary Medical Science, 62, 2000, 243; Kutzler et al. Theriogenology, 60, 2003a, 1187). In cats, some studies have been carried out, but no hormonal parameters for accurate prediction of parturition have been described so far (Buff et al. Journal of Reproduction and Fertility, Suppl. 57, 2001, 187; De Haas van Dorsser et al. Biology of Reproduction, 74, 2006, 1090; DiGangi et al. Journal of the American Veterinary Medical Association, 237, 2010, 1267; Dehnhard et al. Theriogenology, 77, 2012, 1088). Many studies suggested that gestational timing can be obtained by observation using ultrasound or radiography of specific structures in relation to the time of appearance during gestation (Concannon and Rendano American Journal of Veterinary Research, 44, 1983, 1506; Rendano et al. Veterinary Radiology, 25, 1984, 132; Shille and Gontarek Journal of the American Veterinary Medical Association, 187, 1985, 1021; Davidson et al. Veterinary Radiology, 27, 1986, 109; England et al. Journal of Small Animal Practice, 31, 1990, 324; Yeager et al. American Journal of Veterinary Research, 53, 1992, 342; Zambelli et al. Theriogenology, 57, 2002a, 1981; Zambelli et al. Journal of Feline Medicine and Surgery, 4, 2002b, 95; Zambelli and Prati 2006; Lopate Theriogenology, 70, 2008, 397; Davidson and Baker Topics in Companion Animal Medicine, 24, 2009, 55). Ultrasonographic measurement of extra-foetal and foetal structures is a common and accurate method for the prediction of parturition day during pregnancy, when specific formulae are used depending on the ultrasonographic parameter, the species and, in canines, the size of the bitch (Shille and Gontarek Journal of the American Veterinary Medical Association, 187, 1985, 1021; England et al. Journal of Small Animal Practice, 31, 1990, 324; Luvoni and Grioni Journal of Small Animal Practice, 41, 2000, 292; Luvoni and Beccaglia Reproduction in Domestic Animals, 41, 2006, 27; Lopate Theriogenology, 70, 2008, 397; Michel et al. Reproduction in Domestic Animals, 46, 2011, 926; Beccaglia and Luvoni Reproduction in Domestic Animals, 47, 194, 2012). Recent studies demonstrated that in dogs, the imminence of parturition could be predicted by evaluating foetal flux and foetal heart rate by ultrasound (Gil et al. Theriogenology, 82, 2014, 933; Giannico et al., Animal Reproduction Science, 154, 2015, 105). For an accurate prediction of parturition date, the combination of different methods is desirable. PMID- 27670936 TI - Fertility suppression of some wildlife species in southern Africa-a review. AB - Generally speaking, southern Africa's wildlife populations in small-to-medium sized protected game reserves (10,000-65,000 ha) reproduce at rapid rates which often lead overpopulation of certain species. Most commonly these are large predators such as lions, African wild dogs and cheetahs, and elephants. Overpopulation of large predators leads to depletion of prey species, breakouts into neighbouring communities and increased risks for disease transmission. An overabundance of elephants leads to habitat destruction which is to the detriment of not only other herbivores but also certain bird species. By far, the most acceptable and effective method of population control is contraception. Another problem, particularly in South Africa, is the large numbers of large predators that are held in zoos, wildlife sanctuaries or captive breeding facilities. Once again, there is a need for contraception to control the rate of reproduction. In this review, we discuss the methods that have been most commonly used for some wildlife species in southern Africa. The methods include hormonal control and immunocontraception. We also address the problem of androgen-related aggressive behaviours in elephant bulls and giraffe males and present solutions that have been used to ameliorate such behaviours. PMID- 27670937 TI - Advances in endoscopic surgery for small animal reproduction. AB - Although endoscopic surgery entered its "golden era" in the mid-1980s, it is still advancing at a tremendous pace. Novel surgical techniques and devices are continuously developed and applied, and new indications (and/or contraindications) for the use of endoscopic surgery are routinely reported in the literature and subjected to systematic assessments. Although endoscopic surgery (laparoscopy in particular) has already become established as the gold standard in human medicine, it has yet to be proven as a viable alternative to open surgery in the field of veterinary medicine. The advantages of minimally invasive surgery include better intra-operative visualization, reduced postoperative pain, reduced scar formation and increased postoperative mobility. Therefore, it is reasonable to expect that the application of this will continue to expand. Small animal reproduction, a field within the broad discipline of veterinary medicine, has already recognized and begun to reap the benefits of endoscopic surgery. Herein, we retrospectively review the most recent successful novel applications of endoscopic surgery in the small animal reproduction system to provide small animal reproductive surgeons with important knowledge to help improve their own veterinarian medical practice. PMID- 27670939 TI - Evaluation of spermatozoal function-useful tools or just science. AB - Conventional microscopic semen analysis does not provide precise information on the fertilizing potential of a male. The traditional basis for semen evaluation is that male fertility is dependent on production of a "proper" concentration/number of motile, morphologically normal spermatozoa in excess to achieve conception. Many independent studies, especially in human medicine, have demonstrated that the absolute number of spermatozoa does not accurately determine fertility, but their functional competence. Many functional tests of spermatozoa are developed over the last decades. Computer-assisted sperm analysis (CASA) and flow cytometry have become the gold standard for semen assessment in specialized andrology laboratories. Other functional assays, such as gamete interaction tests, provide additional information regarding the real fertilizing potential of sperm cells. From this point of view, such tests are valuable diagnostic tools in fertility disorders and may be helpful to make a decision which method of treatment to use: pharmacological therapy, intrauterine insemination, introduction of classic IVF, ICSI or exclusion from a breeding programme. The most useful gamete interaction tests include induced acrosome reaction, zona pellucida binding assay, oocyte penetration assay and hyaluronan binding assay. In recent years, andrology has entered into a new era of sophisticated OMICS methods. Genomics, epigenomics, transcriptomics and proteomics brought high hopes for rapid progress in clinical diagnostics. PMID- 27670938 TI - Videovaginoscopy of the canine vagina. AB - Endoscopy enables a rapid and non-traumatic examination of the vaginal cavity of female dogs. Its implementation requires specific equipment as well as knowledge about the species-specific vaginal anatomy and the procedure. Vaginoscopy is the diagnostic tool of choice for several vaginal conditions and diseases such as congenital abnormalities, neoplasia or ectopic ureter. Furthermore, vaginal inspection may provide additional information in cases of vulvar discharge or infertility. Vaginoscopy is a superior tool compared to other methods in assisted reproduction. Changes of the vaginal mucosa during the oestrous cycle can be observed to determine the hormonal actions and the time of ovulations in addition to other routine examinations, such as progesterone assay and vaginal cytology. Finally, intrauterine insemination, which is recommended for insemination with frozen-thawed semen, can be performed endoscopically by transcervical catheterization. PMID- 27670940 TI - Assessment of canine neonatal viability-the Apgar score. AB - Perinatal mortality is relatively high in dogs, with deaths peaking around the time of birth and during the first week of age. Among the several causes of canine perinatal mortality, whelping is the greatest cause. Therefore, early neonatal assistance at birth should be mandatory with dogs. In comparison with human neonatology, knowledge and technological ability in canine neonatology is tremendously scarce. The Apgar score for the newborn viability assessment at birth represents a feasible method for the prompt recognition of newborns that will need special assistance immediately after birth. The five parameters of the Apgar score were adapted to the canine species by different studies. Advantages and limits, as well as clinical applications, are presented and discussed in further detail. It was concluded that the Apgar score represents the easiest and simplest, non-invasive and reliable method, that could be performed under every clinical and practical condition, for newborn puppies viability evaluations and short-term survival prognosis. PMID- 27670941 TI - Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection. AB - On Earth, biological systems have evolved in response to environmental stressors, interactions dictated by physical forces that include gravity. The absence of gravity is an extreme stressor and the impact of its absence on biological systems is ill-defined. Astronauts who have spent extended time under conditions of minimal gravity (microgravity) experience an array of biological alterations, including perturbations in cardiovascular function. We hypothesized that physiological perturbations in cardiac function in microgravity may be a consequence of alterations in molecular and organellar dynamics within the cellular milieu of cardiomyocytes. We used a combination of mass spectrometry based approaches to compare the relative abundance and turnover rates of 848 and 196 proteins, respectively, in rat neonatal cardiomyocytes exposed to simulated microgravity or normal gravity. Gene functional enrichment analysis of these data suggested that the protein content and function of the mitochondria, ribosomes, and endoplasmic reticulum were differentially modulated in microgravity. We confirmed experimentally that in microgravity protein synthesis was decreased while apoptosis, cell viability, and protein degradation were largely unaffected. These data support our conclusion that in microgravity cardiomyocytes attempt to maintain mitochondrial homeostasis at the expense of protein synthesis. The overall response to this stress may culminate in cardiac muscle atrophy. PMID- 27670942 TI - Total chemical synthesis, refolding, and crystallographic structure of fully active immunophilin calstabin 2 (FKBP12.6). AB - Synthetic biology (or chemical biology) is a growing field to which the chemical synthesis of proteins, particularly enzymes, makes a fundamental contribution. However, the chemical synthesis of catalytically active proteins (enzymes) remains poorly documented because it is difficult to obtain enough material for biochemical experiments. We chose calstabin, a 107-amino-acid proline isomerase, as a model. We synthesized the enzyme using the native chemical ligation approach and obtained several tens of milligrams. The polypeptide was refolded properly, and we characterized its biophysical properties, measured its catalytic activity, and then crystallized it in order to obtain its tridimensional structure after X ray diffraction. The refolded enzyme was compared to the recombinant, wild-type enzyme. In addition, as a first step of validating the whole process, we incorporated exotic amino acids into the N-terminus. Surprisingly, none of the changes altered the catalytic activities of the corresponding mutants. Using this body of techniques, avenues are now open to further obtain enzymes modified with exotic amino acids in a way that is only barely accessible by molecular biology, obtaining detailed information on the structure-function relationship of enzymes reachable by complete chemical synthesis. PMID- 27670943 TI - Standardized Reporting in IR: A Prospective Multi-Institutional Pilot Study. AB - PURPOSE: To assess adoption and survey-based satisfaction rates following deployment of standardized interventional radiology (IR) procedure reports across multiple institutions. MATERIALS AND METHODS: Standardized reporting templates for 5 common interventional procedures (central venous access, inferior vena cava [IVC] filter insertion, IVC filter removal, uterine artery embolization, and vertebral augmentation) were distributed to 20 IR practices in a prospective quality-improvement study. Participating sites edited the reports according to institutional preferences and deployed them for a 1-year pilot study concluding in July 2015. Study compliance was measured by sampling 20 reports of each procedure type at each institution, and surveys of interventionalists and referring physicians were performed. Modifications to the standardized reporting templates at each site were analyzed. RESULTS: Ten institutions deployed the standardized reports, with 8 achieving deployment of 3-12 months. The mean report usage rate was 57%. Each site modified the original reports, with 26% mean reduction in length, 18% mean reduction in wordiness, and 60% mean reduction in the number of forced fill-in fields requiring user input. Linear-regression analysis revealed that reduced number of forced fill-in fields correlated significantly with increased usage rate (R2 = 0.444; P = .05). Surveys revealed high satisfaction rates among referring physicians but lower satisfaction rates among interventional radiologists. CONCLUSIONS: Standardized report adoption rates increased when reports were simplified by reducing the number of forced fill-in fields. Referring physicians preferred the standardized reports, whereas interventional radiologists preferred standard narrative reports. PMID- 27670944 TI - HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production. AB - In inflammatory bowel diseases (IBD), high mobility group box 1 (HMGB1), as an endogenous inflammatory molecule, can promote inflammatory cytokines secretion by acting on TLR2/4 resulting in tissue damage. The underlying mechanisms remain unclear. Here we report a novel role of HMGB1 in controlling the maintenance and function of intestine-resident group-3 innate lymphoid cells (ILC3s) that are important innate effector cells implicated in mucosal homeostasis and IBD pathogenesis. We showed that mice treated with anti-HMGB1 Ab, or genetically deficient for TLR2-/- or TLR4-/- mice, displayed reduced intestinal inflammation. In these mice, the numbers of colonic ILC3s were significantly reduced, and the levels of IL-17 and IL-22 that can be secreted by ILC3s were also decreased in the colon tissues. Furthermore, HMGB1 promoted DCs via TLR2/4 signaling to produce IL-23, activating ILC3s to produce IL-17 and IL-22. Our data thus indicated that the HMGB1-TLR2/4-DCs-IL-23 cascade pathway enhances the functions of ILC3s to produce IL-17 and IL-22, and this signal way might play a vital role in the development of IBD. PMID- 27670946 TI - Autophagy is induced by anti-neutrophil cytoplasmic Abs and promotes neutrophil extracellular traps formation. AB - Dysregulated neutrophil extracellular traps (NETs) formation contributes to the pathogenesis of anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis (AAV). Increasing evidence indicates that autophagy is involved in the process of NETs formation. In this study, we aimed to investigate whether ANCA could induce autophagy in the process of NETs formation. Autophagy was detected using live cell imaging, microtubule-associated protein light chain 3B (LC3B) accumulation and Western blotting. The results showed that autophagy vacuolization was detected in neutrophils treated with ANCA-positive IgG by live cell imaging. This effect was enhanced by rapamycin, the autophagy inducer, and weakened by 3 methyladenine (3-MA), the autophagy inhibitor. In line with these results, the autophagy marker, LC3B, showed a punctate distribution pattern in the neutrophils stimulated with ANCA-positive IgG. In the presence of rapamycin, LC3B accumulation was further increased; however, this effect was attenuated by 3-MA. Moreover, incubated with ANCA-positive IgG, the NETosis rate significantly increased compared with the unstimulated group. And, the rate significantly increased or decreased in the neutrophils pretreated with rapamycin or 3-MA, respectively, as compared with the cells incubated with ANCA-positive IgG. Overall, this study demonstrates that autophagy is induced by ANCA and promotes ANCA-induced NETs formation. PMID- 27670945 TI - Regulation of the IL-10-driven macrophage phenotype under incoherent stimuli. AB - Macrophages are ubiquitous innate immune cells that play a central role in health and disease by adopting distinct phenotypes, which are broadly divided into classical inflammatory responses and alternative responses that promote immune suppression and wound healing. Although macrophages are attractive therapeutic targets, incomplete understanding of this functional choice limits clinical manipulation. While individual stimuli, pathways, and genes involved in macrophage functional responses have been identified, how macrophages evaluate complex in vivo milieus comprising multiple divergent stimuli remains poorly understood. Here, we used combinations of "incoherent" stimuli-those that individually promote distinct macrophage phenotypes-to elucidate how the immunosuppressive, IL-10-driven macrophage phenotype is induced, maintained, and modulated under such combinatorial stimuli. The IL-10-induced immunosuppressive phenotype was largely insensitive to co-administered IL-12, which has been reported to modulate macrophage phenotype, but maintaining the immunosuppressive phenotype required sustained exposure to IL-10. Our data implicate the intracellular protein, BCL3, as a key mediator of the IL-10-driven phenotype. Notably, co-administration of IFN-gamma disrupted an IL-10-mediated positive feedback loop that may reinforce the immunosuppressive phenotype. This novel combinatorial perturbation approach thus generated new insights into macrophage decision making and local immune network function. PMID- 27670947 TI - Piperacillin/tazobactam-induced immune-mediated thrombocytopenia in the intensive care unit. AB - WHAT IS KNOWN AND OBJECTIVE: Drug-induced immune-mediated thrombocytopenia is a rare adverse event that remains a diagnostic challenge, especially in the critically ill population. There are only two previously reported cases of rapid and profound thrombocytopenia after administration of piperacillin/tazobactam. CASE SUMMARY: A 64-year-old man experienced several episodes of isolated thrombocytopenia after receiving piperacillin/tazobactam. Interestingly, the degree of thrombocytopenia varied with the amount of corticosteroid therapy the patient was receiving. Due to the complexity of thrombocytopenia in critically ill patients, other potential causes were extensively worked up and ruled out. WHAT IS NEW AND CONCLUSION: We describe the first case of piperacillin/tazobactam induced immune-mediated thrombocytopenia that was mitigated by the administration of corticosteroid therapy. This case highlights the importance of identifying potential drug-related causes of isolated thrombocytopenia. PMID- 27670949 TI - Pretransplant patient, parent, and family psychosocial functioning varies by organ type and patient age. AB - The goal of this study was to compare pretransplant patient HRQOL, parent psychological functioning, and the impact of the patient's ongoing illness on the family between organ types (ie, kidney, liver, heart) and age-groups (ie, children, AYAs). The sample included 80 pediatric patients with end-stage organ disease who were evaluated for transplantation and their parents. Parents completed self- and proxy reports at patients' pretransplant evaluations. Results indicated that patients evaluated for heart transplants consistently had lower HRQOL and their parents had greater psychological distress compared to the kidney and liver groups. Within the heart group, parents and families of children (<12 years old) experienced significantly more distress and impact of the patient's illness on the family compared to those of AYAs (>=12 years old). Pediatric patients awaiting heart transplants, particularly younger children, and their parents and families may have greater psychosocial needs compared to patients awaiting kidney or liver transplants. PMID- 27670950 TI - Should we redefine the classic lateral pallium? AB - The quadripartite model of the telencephalic pallium of amniotes offered by the Puelles school includes a medial, dorsal, lateral, and ventral pallium. Watson and Puelles ([2016] J. Comp. Neurol. this issue) now newly propose that the mammalian ventral pallium gives rise not only to all of the pallial amygdala but also to the olfactory cortex, which hitherto was considered to arise from the lateral pallium. Thus, the region of the lateral pallium was misidentified in the quadripartite model, as the designated histogenetic unit gives rise to the insular cortex/claustrum and should therefore be considered a most ventrolateral part of the dorsal pallium (its ventrolateral subdivision). The mesopallium of birds then is the homologue of this ventrolateral dorsal pallial part, not of the classic lateral pallium. The region designated as the ventral pallium in the initial quadripartite model should therefore be divided in the new Watson/Puelles model into a smaller ventral pallium and a lateral pallium. J. Comp. Neurol. 525:1509-1513, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27670951 TI - The function of the DegP (HtrA) protein: Protease versus chaperone. AB - The DegP (or HtrA) is a highly conserved family of proteins functioning in all living organisms. It was initially identified as a protease functioning in the periplasmic space of the Gram-negative bacterial cells. It was later reported to also exhibit chaperone activity and thus has been designated as a bifunctional protein. However, recent studies demonstrated that in living cells it more likely functions only as a protease with hardly detectable chaperone activities. In this review, I will summarize the evidences clarifying that DegP more likely only functions as a protease rather than as a chaperone in cells. (c) 2016 IUBMB Life, 68(11):904-907, 2016. PMID- 27670953 TI - Stretchable Materials for Robust Soft Actuators towards Assistive Wearable Devices. AB - Soft actuators made from elastomeric active materials can find widespread potential implementation in a variety of applications ranging from assistive wearable technologies targeted at biomedical rehabilitation or assistance with activities of daily living, bioinspired and biomimetic systems, to gripping and manipulating fragile objects, and adaptable locomotion. In this manuscript, we propose a novel two-component soft actuator design and design tool that produces actuators targeted towards these applications with enhanced mechanical performance and manufacturability. Our numerical models developed using the finite element method can predict the actuator behavior at large mechanical strains to allow efficient design iterations for system optimization. Based on two distinctive actuator prototypes' (linear and bending actuators) experimental results that include free displacement and blocked-forces, we have validated the efficacy of the numerical models. The presented extensive investigation of mechanical performance for soft actuators with varying geometric parameters demonstrates the practical application of the design tool, and the robustness of the actuator hardware design, towards diverse soft robotic systems for a wide set of assistive wearable technologies, including replicating the motion of several parts of the human body. PMID- 27670952 TI - Auto-Amputation of the Breast; a Rare Case Caused by Invasive Ductal Carcinoma. PMID- 27670954 TI - Quantification of dimethylsulfoxide (DMSO) in equine plasma and urine using HILIC MS/MS. AB - This paper describes quantitative methods for the determination of dimethylsulfoxide (DMSO) in equine plasma and urine based on simple precipitation and dilution followed by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS/MS). DMSO is a polar solvent with analgesic and anti-inflammatory properties. Its pharmacological features make it prohibited in horse racing. However, since DMSO is naturally present in the horses' environment, international threshold values have been implemented for plasma and urine (1 and 15 ug/mL, respectively). Previously presented quantitative methods for the determination of DMSO are based on gas chromatography, thus demanding a tedious extraction step to transfer the analyte from the aqueous bodily fluid to an injectable organic solvent. The column used in the presented method was an Acquity BEH HILIC and the mobile phase was a mixture of ammonium acetate buffer and acetonitrile delivered as a gradient. Hexadeuterated DMSO (2 H6 -DMSO) was used as the internal standard. Validation was performed in the range of the international thresholds concerning selectivity, carry-over, linearity, precision, accuracy, stability and inter-individual matrix variation. The results fulfilled the predefined criteria and the methods were considered fit for purpose. Successful applications on real equine doping control samples were carried out with determined DMSO concentrations exceeding the international thresholds. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27670955 TI - Perovskite Solar Cells on Corrugated Substrates with Enhanced Efficiency. AB - Organometallic halide perovskites solar cells are fabricated on nano-scaled corrugated substrates using a sequential deposition method. The corrugated substrates are fabricated using colloidal lithography followed by reactive ion etching. The corrugated structure is found to accelerate the chemical reaction between the sequentially deposited lead iodide (PbI2 ) and methyl ammonium iodide layers to form stoichiometric perovskite films, and the corrugated morphology is preserved at the interface of the hole transport layer (HTL) and the perovskite layer. The shunt resistance of the corrugated devices is found to be higher than that of the planar devices, leading to a higher open circuit voltage (VOC ) and fill factor (FF) in the corrugated devices. Finite-difference time-domain simulation is carried out on both planar and corrugated devices. The results revealed that light absorption is enhanced in the corrugated devices due to the corrugated HTL/perovskite interface, resulting in a significantly higher short circuit current (JSC ) observed in the corrugated devices. As a result, the average power conversion efficiency increases from 8.7% for the planar devices to 13% for the corrugated devices. PMID- 27670948 TI - Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences. PMID- 27670956 TI - Repeat Imaging in Idiopathic Unilateral Vocal Fold Paralysis: Is It Necessary? AB - OBJECTIVE: Imaging plays a critical role in the evaluation of patients presenting with unilateral vocal fold paresis or paralysis of unknown etiology. In those with idiopathic unilateral vocal fold paralysis (iUVFP), there is no consensus regarding the need or timing of repeat imaging. This study seeks to establish the rate of delayed detection of alternate etiologies for these patients to determine if and when imaging should be repeated. METHODS: Retrospective chart review was conducted identifying patients at our institution with vocal fold movement impairment between 1998 and 2014. Idiopathic paralysis was diagnosed if physical examination, laryngoscopy, and initial imaging excluded a cause. Demographic data, length of follow-up, and the presence of late lesions were noted. Time to detection was plotted using the Kaplan-Meier method. RESULTS: Of 3210 patients reviewed, 207 had a diagnosis of iUVFP. Of these patients, 8 went on to develop alternate diagnoses, including pulmonary disease, skull-base and laryngeal neoplasms, and thyroid malignancy. In Kaplan-Meir analysis, 90% remained "idiopathic" at 5 years of follow-up. The mean time to detection was 27 months. CONCLUSIONS: Patients initially diagnosed with iUVFP may have an occult cause that later becomes evident. We recommend repeat imaging within 2 years after diagnosis, but this is likely unnecessary beyond 5 years. PMID- 27670957 TI - Interactive iPhone/iPad App for Increased Tympanic Membrane Familiarity. AB - INTRODUCTION: Otology relies on clinical examination to teach anatomy of the ear. The purpose of this report is to introduce the Buckingham Virtual Tympanum iPhone app as an adjuvant educational tool to teach the anatomical details of the tympanic membrane (TM). MATERIALS AND METHODS: This app, available free at the Apple Store, was constructed using archival photographs of normal and abnormal TMs, stratified by difficulty. Each image has 4 labeled structures, linked to questions to encourage active learning. Third-year medical students then used the app to familiarize themselves with the TM. RESULTS: The free app was readily accessible and functioned without technical issues. By being interactive, it forced the user into the role of active learner. This pilot study found that students who used the app understood images of the TM better than those who did not use it. DISCUSSION: We introduce an interactive, iPhone-based smartphone application that we found to be a useful adjunct for teaching TM anatomy. PMID- 27670958 TI - Beneficial effects of mucous fistula refeeding in necrotizing enterocolitis neonates with enterostomies. AB - BACKGROUND: Necrotizing enterocolitis in premature neonates often results in bowel resection and stoma formation. One way to promote bowel adaptation before stoma closure is to introduce proximal loop effluents into the mucous fistula. In this study, we reviewed our experience with distal loop refeeding with respect to control group. METHODS: All patients with necrotizing enterocolitis between 2000 and 2014 necessitating initial diverting enterostomies and subsequent stoma closure in a tertiary referral center were included. Medical records were retrospectively reviewed. Demographic data, surgical procedures, and postoperative outcomes were analyzed. RESULTS: 92 patients were identified, with 77 patients receiving mucous fistula refeeding. The refeeding group showed less bowel ends size discrepancy (25 vs 53%, p=0.034) and less postoperative anastomotic leakage (3 vs 20%, p=0.029). Fewer refeeding group patients developed parenteral nutrition related cholestasis (42 vs 73%, p=0.045) and required shorter parenteral nutrition support (47 vs 135days, p=0.002). The mean peak bilirubin level was higher in the non-refeeding group (155 vs 275MUmol/L, p<0.001). No major complication was associated with refeeding. CONCLUSIONS: Mucous fistula refeeding is safe and can decrease risk of anastomotic complication and parental nutrition related cholestasis. It provides both diagnostic and therapeutic value preoperatively and its use should be advocated. Level III Treatment Study in a Case Control Manner. PMID- 27670959 TI - Mitigation of stomach dehiscence risk during gastrostomy tube changes - a retrospective analysis of patient outcomes. AB - INTRODUCTION: Stomach dehiscence from the abdominal wall is a serious and potentially life-threatening complication of gastrostomy tube changes. This retrospective study evaluates gastric aspiration as an inexpensive and safe alternative to endoscopic or radiographic confirmation. METHODS: From August 1998 to June 2016, 682 patients (301 female, 381 male) underwent 1713 gastrostomy tube changes in the medical setting, with an average age of 7.59years and an average site age of 3.43years. The most common diagnoses were GERD (304), aspiration (168), and failure to thrive (143). RESULTS: All newly inserted tubes were aspirated to visually inspect for gastric fluid. This procedure as a confirmatory test for intragastric placement was found to have a positive predictive value of 99.5% and negative predictive value of 77.8%, with a sensitivity of 99.8% and specificity of 63.6%. In cases with successful aspiration of gastric fluid, 75.5% of changes resulted in no complications, with intraperitoneal insertion or leak in only 0.48% of cases. CONCLUSIONS: Positive gastric aspirate is a strong predictor of proper G-tube placement with high sensitivity, eliminating the requirement of specialized equipment and the cost associated with endoscopic or radiographic guidance, and has a comparable or superior risk profile. LEVELS OF EVIDENCE: Study of diagnostic test level II. PMID- 27670960 TI - Diagnostic value of rectal suction biopsies using calretinin immunohistochemical staining in Hirschsprung's disease. AB - BACKGROUND: The study investigates the diagnostic value of calretinin immunohistochemical staining (CIS) on rectal suction biopsies (RSB) in Hirschsprung's disease (HD). METHODS: A prospective study was conducted at Children's Hospital 2 in Ho Chi Minh City, Vietnam, from January through December 2015. Patients suspected of HD during this period underwent RSB and were followed in order to assess the accuracy of the diagnostic test with CIS compared with conventional histology (H&E). RESULTS: A total of 188 children with RSB were investigated. Median age was 7.1 (range 0.2-159) months with 65.4% boys. HD was confirmed in 80 (42.6%) children. There were 1 false positive and no false negative cases. The sensitivity and specificity were 100% (80/80) and 99.1% (107/108) for CIS and 100% and 85.2% for H&E, respectively. Cohen's kappa coefficient was 0.9891 with a diagnostic accuracy of 99.5% for CIS, compared with 0.8303 and 91.5% for H&E, respectively. There were no serious complications related to the RSB. CONCLUSION: RSB with CIS is a useful diagnostic method for HD, with easy interpretation and no need for cryostat. CIS has a high diagnostic accuracy and should be considered as the primary method for the diagnosis of HD by RSB. LEVEL OF EVIDENCE: Diagnostic Studies - Level I. PMID- 27670961 TI - Injuries and outcomes associated with recreational vehicle accidents in pediatric trauma. AB - PURPOSE: To identify injuries and outcomes from Recreational/Off-Highway Vehicles (RV/OHV) accidents at a pediatric trauma center. METHODS: A retrospective review of a prospective pediatric trauma registry was performed to identify patients sustaining injuries from an RV/OHV between January 2007 and July 2015. Vehicles included: all-terrain vehicles (ATV), dirt bikes, utility-terrain vehicles (UTV), golf carts, go-karts, and dune buggies. RESULTS: Five hundred twenty-eight patients were injured while on an RV/OHV: 269 ATV, 135 dirt bike, 42 UTV, 38 golf cart, 34 go-kart, and 10 dune buggy. The majority (n=381, 72%) had at least one injury with an Abbreviated Injury Scale >=2; 39% (n=204) had orthopedic injuries and 22% (n=116) had central neurologic injuries. Over three-fourths (n=412, 78%) were admitted. For the 48% (n=253) of patients requiring surgery, 654 surgical procedures were performed. Median hospital charge was $27,565 (IQR: $15,553 $44,935). Excluding golf carts, helmet use was 49% (n=231); 16% (n=76) wore protective clothing. Only 22% (n=26) wore a restraining belt. CONCLUSION: Severe injuries occur in children who ride RV/OHV often warranting admission and surgical intervention. Improved understanding of RV/OHV injuries may guide caregivers in decision-making about pediatric RV/OHV use and encourage use of protective gear. LEVEL OF EVIDENCE: Level II, Prognosis Study. PMID- 27670962 TI - Enterocolitis and bowel function in children with Hirschsprung disease and trisomy 21. AB - BACKGROUND/PURPOSE: The purpose of this study was to study the effect of trisomy 21 (T21) on enterocolitis rates and bowel function among children with Hirschsprung disease (HD). METHODS: A retrospective cohort study of patients with HD treated at our tertiary children's hospital (2000-2015) and a cohort of patients with HD treated in our pediatric colorectal center (CRC) (2011-2015) were performed. RESULTS: 26/207 (13%) patients with HD had T21. 70 (41%) with HD alone were diagnosed with enterocolitis episodes compared to 9 (38%) with HD+T21 (p=0.71). 55/207 patients were managed in the CRC. 11/55 patients (20%) had HD+T21. 25 (58%) with HD had one or more enterocolitis episodes compared to 4 (36%) with HD+T21 (p=0.20). Number of hospitalizations for enterocolitis was similar between all groups. Toilet training was assessed in 32 CRC patients (25 HD, 7 HD+T21). One child with HD+T21 was toilet trained by age 4years versus 12 with HD (p=0.20). Laxative or enema therapy was required for constipation management in 57% HD versus 64% HD+T21. CONCLUSION: Enterocolitis rates in children with HD+T21 did not differ from rates in children with HD alone. The majority of patients with CRC follow-up had constipation requiring laxative or enema therapy, which demonstrates the need for consistent postoperative follow up. LEVEL OF EVIDENCE: Retrospective Study - Level II. PMID- 27670963 TI - Benchmarking the value of ultrasound for acute appendicitis in children. AB - BACKGROUND: This study appraises the diagnostic quality of ultrasound for acute appendicitis in children and consequently challenges the perception of inferior accuracy and suitability compared to computed tomography (CT). METHODS: Radiologist reports for consecutive "query appendicitis" ultrasound studies were retrieved from a hospital database for the study period 2009-2014. Children who subsequently underwent appendicectomy were identified. Corresponding operative and histopathology findings were evaluated. Diagnostic accuracy of ultrasound was determined by analyzing overall accuracy, sensitivity, specificity, predictivity, and likelihood ratios. RESULTS: A total of 3799 ultrasound examinations were evaluated. Mean age was 11.5+/-3.8years. The proportion of patients investigated with preoperative ultrasound was 59.9% (1103/1840). Appendix visualization rate was 91.7%. Overall diagnostic accuracy was 95.5%. Sensitivity and specificity values were 97.1% (95.9-98.1; 95% CI) and 94.8% (93.9-95.6; 95% CI), respectively. Separate analysis of only ultrasound positive and negative examinations (i.e., excluding nondiagnostic examinations) confirmed sensitivity and specificity values of 98.8% and 98.3%. CONCLUSION: In this largest reported single institution series of ultrasound examinations for appendicitis, we report benchmark standard quality of diagnostic accuracy and visualization rates. Given the radiation and cost implications of CT, there is a strong argument to recommend ultrasound as the primary imaging modality. Diagnostic Study-Level II. PMID- 27670964 TI - Biodegradable polydioxanone stent as a new treatment strategy for tracheal stenosis in a rabbit model. AB - PURPOSE: Congenital tracheal stenosis (CTS) is a rare condition and difficult to treat. Slide tracheoplasty has unsatisfactory outcomes for severe neonatal symptomatic CTS. This study evaluated the use of biodegradable polydioxanone stents (BD stent) in a rabbit model of CTS. METHODS: Tracheal stenosis was induced in female Japanese white rabbits, 9-10weeks old, by direct scraping of the tracheal mucosa with a nylon brush following transverse incision of the trachea (control group, n=4). Seven days later, we incised the trachea again and inserted a BD stent (15*5mm) into the trachea (stent group, n=4). Arterial blood gas analysis was performed twice weekly for 1month after the procedure. RESULTS: In the control group, respiratory acidosis arising from ventilatory failure was observed on postoperative days 7-10. Rabbits were sacrificed at 11.5days after scraping. Severe tracheal stenosis resulting from inflammatory granulation was detected in the scraped region in all rabbits. In the stent group, arterial blood gas analysis was normal at 28days after stent insertion. The BD stent maintained patency of the tracheal lumen and prolonged survival for 1month. CONCLUSIONS: The use of BD stent represents a promising new treatment method for tracheal stenosis. PMID- 27670965 TI - The development of targeted new agents to improve the outcome for children with leukemia. AB - INTRODUCTION: Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias. A comprehensive description of the biological background, adult data and early clinical trials in pediatrics is provided. Expert opinion: Clinical trials are the way to evaluate new agents in pediatric cancer. The development of new drugs in pediatric leukemia must be preceded by a solid biological rationale. Agents in development exploit all possible vulnerabilities of leukemic cells. Drugs targeting cell surface antigens, intracellular signaling pathways and cell cycle inhibitors or epigenetic regulators are most prominent. Major advances have occurred thanks to new developments in engineering leading to optimized molecules such as anti-CD19 bi-specific T-cell engagers (e.g. blinatumomab) and antibody-drug conjugates. The integration of new-targeted therapies in pediatric chemotherapy-based regimens will lead to improved outcomes. PMID- 27670966 TI - Valvular heart disease and pregnancy part II: management of prosthetic valves. PMID- 27670968 TI - Identifying anticancer peptides by using improved hybrid compositions. AB - Cancer is one of the main causes of threats to human life. Identification of anticancer peptides is important for developing effective anticancer drugs. In this paper, we developed an improved predictor to identify the anticancer peptides. The amino acid composition (AAC), the average chemical shifts (acACS) and the reduced amino acid composition (RAAC) were selected to predict the anticancer peptides by using the support vector machine (SVM). The overall prediction accuracy reaches to 93.61% in jackknife test. The results indicated that the combined parameter was helpful to the prediction for anticancer peptides. PMID- 27670969 TI - Determining prescription durations based on the parametric waiting time distribution. AB - PURPOSE: The purpose of the study is to develop a method to estimate the duration of single prescriptions in pharmacoepidemiological studies when the single prescription duration is not available. METHODS: We developed an estimation algorithm based on maximum likelihood estimation of a parametric two-component mixture model for the waiting time distribution (WTD). The distribution component for prevalent users estimates the forward recurrence density (FRD), which is related to the distribution of time between subsequent prescription redemptions, the inter-arrival density (IAD), for users in continued treatment. We exploited this to estimate percentiles of the IAD by inversion of the estimated FRD and defined the duration of a prescription as the time within which 80% of current users will have presented themselves again. Statistical properties were examined in simulation studies, and the method was applied to empirical data for four model drugs: non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, bendroflumethiazide, and levothyroxine. RESULTS: Simulation studies found negligible bias when the data-generating model for the IAD coincided with the FRD used in the WTD estimation (Log-Normal). When the IAD consisted of a mixture of two Log-Normal distributions, but was analyzed with a single Log-Normal distribution, relative bias did not exceed 9%. Using a Log-Normal FRD, we estimated prescription durations of 117, 91, 137, and 118 days for NSAIDs, warfarin, bendroflumethiazide, and levothyroxine, respectively. Similar results were found with a Weibull FRD. CONCLUSIONS: The algorithm allows valid estimation of single prescription durations, especially when the WTD reliably separates current users from incident users, and may replace ad-hoc decision rules in automated implementations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27670970 TI - Close Obs. PMID- 27670971 TI - Recovery. PMID- 27670972 TI - Styx and Sarcoma. PMID- 27670967 TI - Estimated glomerular filtration rate and urine biomarkers in patients with single ventricle Fontan circulation. AB - OBJECTIVES: To define whether adults with a Fontan circulation, who have lifelong venous congestion and limited cardiac output, have impaired glomerular filtration rate (GFR) or elevated urinary biomarkers of kidney injury. METHODS: We measured circulating cystatin C and creatinine (n=70) and urinary creatinine, albumin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl glucosaminidase (NAG) (n=59) in ambulatory adult Fontan patients and 20 age-matched and sex-matched controls. Urinary biomarkers were normalised to urine creatinine concentration. Survival free from non-elective cardiovascular hospitalisation was compared by estimated GFR and urinary biomarker levels using survival analysis. RESULTS: Cystatin C GFR was lower in the Fontan group compared with controls (114.2+/-22.8 vs 136.3+/-12.8 mL/min/1.73 m2, p<0.0001); GFR<90 mL/min/1.73 m2 in 14.3% vs 0% of controls. Albumin-to creatinine ratio (ACR), KIM-1 and NAG were elevated compared with controls; ACR=23.2 (7.6-38.3) vs 3.6 (2.5-5.7) mg/g, p<0.0001; NAG=1.8 (1.1-2.6) vs 1.1 (0.9-1.6) U/g, p=0.02; KIM-1=0.91 (0.52-1.45) vs 0.33 (0.24-0.74) ng/mg, p=0.001. Microalbuminuria, ACR>30 mg/g, was present in 33.9% of the Fontan patients but in none of the controls. Over median 707 (IQR 371-942)-day follow-up, 31.4% of patients had a clinical event. Higher KIM-1 and NAG were associated with higher risk of non-elective hospitalisation or death (HR/+1 SD=2.1, 95% CI 1.3 to 3.3, p=0.002; HR/+1 SD=1.6, 95% CI 1.05 to 2.4, p=0.03, respectively); cystatin C GFR was associated with risk of the outcome (HR/+1 SD=0.66, 95% CI 0.48 to 0.90, p=0.009) but creatinine-based GFR was not (HR/+1 SD=0.91, 95% CI 0.61 to 1.38, p=0.66). Neither ACR nor NGAL was associated with events. CONCLUSIONS: The Fontan circulation is commonly associated with reduced estimated GFR and evidence for glomerular and tubular injury. Those with lower cystatin C GFR and tubular injury are at increased risk of adverse outcomes. PMID- 27670973 TI - A fuller picture: evaluating an art therapy programme in a multidisciplinary mental health service. AB - Art therapy has a long history in mental healthcare, but requires an enhanced evidence base in order to better identify its precise role in contemporary services. This paper describes an evaluation of an art therapy programme in an acute adult psychiatry admission unit in Ireland. A mixed method research design was used. Quantitative data were collected through a survey of 35 staff members and 11 service users. Qualitative data included free text comments collected in the survey and individual feedback from service users. Both methods aimed to assess the role of art therapy as part of a multidisciplinary mental health service. Thematic content analysis was employed to analyse qualitative data. Staff demonstrated overwhelming support for art therapy as one element within multidisciplinary services available to patients in the acute psychiatry setting, Qualitative feedback associated art therapy with improvements in quality of life and individual support, and emphasised its role as a non-verbal intervention, especially useful for those who find talking therapy difficult. Creative self expression is valued by staff and service users as part of the recovery process. Recommendations arising from the research include continuing the art therapy service, expanding it to include patients under rehabilitation, provision of information and education sessions to staff, and further research to identify other potential long-term effects. The low response of staff and small sample in this study, however, must be noted as limitations to these findings. PMID- 27670974 TI - Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers. AB - 1. The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy volunteers. 2. An open-label, two period, sequential study was conducted in 12 healthy volunteers. A single dose of PIP 20 mg was administered daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed by HPLC. 3. Treatment with PIP significantly enhanced maximum plasma concentration (Cmax) (3.14-4.96 MUg/mL), area under the curve (AUC) (10.46-17.78 MUg h/mL), half life (T1/2) (1.26-1.82 h) and significantly decreased elimination rate constant (Kel) (0.57-0.41 h - 1), apparent oral clearance (CL/F) (24.76 13.65 L/h) of CHZ when compared to control. In addition, treatment with PIP significantly decreased Cmax (0.22-0.15 MUg/mL), AUC (0.94-0.68 MUg h/mL), T1/2 (2.54-1.68 h) and significantly increased Kel (0.32-0.43 h - 1) of 6 hydroxychlorzoxazone (6-OHCHZ) as compared to control. Furthermore, treatment with PIP significantly decreased metabolite to parent (6-OHCHZ/CHZ) ratios of Cmax, AUC, T1/2 and significantly increased Kel ratio of 6-OHCHZ/CHZ, which indicate the decreased formation of CHZ to 6-OHCHZ. 4. The results suggest that altered pharmacokinetics of CHZ might be attributed to PIP mediated inhibition of CYP2E1 enzyme, which indicate significant pharmacokinetic interaction present between PIP and CHZ. The inhibition of CYP2E1 by PIP may represent a novel therapeutic benefit for minimizing ethanol induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol. PMID- 27670975 TI - Integration and Typologies of Vulnerability to Climate Change: A Case Study from Australian Wheat Sheep Zones. AB - Although the integrated indicator methods have become popular for assessing vulnerability to climate change, their proliferation has introduced a confusing array of scales and indicators that cause a science-policy gap. I argue for a clear adaptation pathway in an "integrative typology" of regional vulnerability that matches appropriate scales, optimal measurements and adaptive strategies in a six-dimensional and multi-level analysis framework of integration and typology inspired by the "5W1H" questions: "Who is concerned about how to adapt to the vulnerability of what to what in some place (where) at some time (when)?" Using the case of the vulnerability of wheat, barley and oats to drought in Australian wheat sheep zones during 1978-1999, I answer the "5W1H" questions through establishing the "six typologies" framework. I then optimize the measurement of vulnerability through contrasting twelve kinds of vulnerability scores with the divergence of crops yields from their regional mean. Through identifying the socioeconomic constraints, I propose seven generic types of crop-drought vulnerability and local adaptive strategy. Our results illustrate that the process of assessing vulnerability and selecting adaptations can be enhanced using a combination of integration, optimization and typology, which emphasize dynamic transitions and transformations between integration and typology. PMID- 27670976 TI - Correctional psychopharmacology: pitfalls, challenges, and victories of prescribing in a correctional setting. AB - Mentally ill patients are entering the criminal justice system at alarming rates, representing a significant percentage of those incarcerated. Correctional facilities are mandated to provide mental health treatment to inmates. The increasing number of inmate patients has made psychiatry an important part of institutional operations. Psychiatrists are called to provide psychopharmacological interventions to aid in the safe operation of institutions and provide effective treatment to those with mental illness. This article discusses the uniqueness of prescribing within correctional settings and delineates important aspects of correctional psychiatry. It includes information on navigating the rigid structure of correctional environments, providing effective interventions for behaviourally disruptive and manipulative inmates, prescribing within the limits of formulary restrictions, considerations for dispensing medication, preventing medication diversion, involuntarily medication practices, and treatment of aggressive inmates. The article concludes with case illustrations that depict the pitfalls, challenges, and victories of working with inmate patients. PMID- 27670977 TI - Effect of cumulative repetitive transcranial magnetic stimulation on freezing of gait in patients with atypical Parkinsonism: A pilot study. AB - OBJECTIVE: To investigate the potential of cumulative high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on freezing of gait in atypical Parkinsonism. DESIGN: Randomized, single-blinded, crossover study with a blinded observer. PARTICIPANTS: Eight patients with atypical Parkinsonism. METHODS: All participants received HF-rTMS over the lower leg primary motor cortex (M1-LL) for 5 consecutive days. Alternative sham stimulation was also administered with a 2 week wash-out period. Freezing of Gait Questionnaire (FOG-Q), turn steps in the modified Standing Start 180 degrees Turn Test, the Timed Up and Go (TUG) task, and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) were performed before, after, and one week after rTMS. RESULTS: All participants completed this study without any significant adverse effects. FOG-Q and turn steps revealed significant improvements over time in the rTMS compared with the sham stimulation (chi2=6.067, p=0.048 and chi2=9.083, p=0.011). In addition, the TUG task and UPDRS-III showed significant improvements over time in the rTMS compared with the sham stimulation (chi2=7.200, p=0.02 and chi2=7.000, p=0.030). CONCLUSION: Cumulative HF-rTMS over the M1-LL might be effective for improving freezing of gait in patients with atypical Parkinsonism. Further investigation with a large number of participants is needed to clarify the effects of HF- rTMS on freezing of gait in atypical Parkinsonism. PMID- 27670978 TI - Caught in the Cross-Fire. AB - A psychiatrist's review of the state of knowledge about the effects of pornography and the reasons for the ferocious arguments on the subject. PMID- 27670979 TI - Confusion Reigns. AB - The ex-film censor looks at the way ideas about what is Pornographic alter and suggests that although times change only some people change with them. PMID- 27670980 TI - Under Control. AB - The new film of David Mercer's Family life poses some hard questions for psychiatry to answer and puts the Laingian case for 'schizophrenia' being an illness created within the family unit. PMID- 27670982 TI - News Review. PMID- 27670981 TI - With the Eyes of a Child. AB - Children's art can be a guide to their rate of development and can also help to establish the reasons for disturbed behaviour. PMID- 27670983 TI - Scan. AB - A personal view of the social services. PMID- 27670984 TI - Utopia on the Rocks. AB - Analysing American society and finding little hope for it has almost become a 'favourite sport' for sociologists. Another book on this theme illustrates the strongly-felt and yet somehow 'manufactured' crisis of conscience in the USA. PMID- 27670986 TI - From Where I Sit: Editorial Comment. PMID- 27670985 TI - Insights Through Art. AB - For some reason art therapy is often viewed with tolerant amusement but, in fact, it often has a really 'solid' contribution to make to the treatment and recovery of the mentally ill. PMID- 27670987 TI - First-Class Citizenship. AB - As a right, the mentally handicap deserve to live and work in the community to which they belong rather than being separated from it in the name of special treatment. A challenging new project in Sheffield, based on this principle, is just getting underway. PMID- 27670988 TI - Power to the Manager. AB - The president of the Blue Cross Association of America thinks, among other things, that the National Health Service should have 'hospital managers' and an interrelation of its 'private' and 'public' sectors. A review of his contribution to a book suggesting radical remedies. PMID- 27670989 TI - Let Be Be Finale of Seem: The Safety and Effectiveness of Inferior Vena Cava Filters. PMID- 27670990 TI - The Angiomyolipoma Conundrum. PMID- 27670991 TI - Percutaneous Esophagogastrostomy Creation for Gastric Bypass Reversal. PMID- 27670992 TI - Percutaneous Removal of Retained Bullet. PMID- 27670994 TI - Cryoablation of Facial Arteriovenous Malformations: Expanding the Scope of Treatment. PMID- 27670993 TI - Treatment of Residual Facial Arteriovenous Malformations after Embolization with Percutaneous Cryotherapy. AB - This report presents 4 patients (mean age, 22 y; range, 17-26 y) with facial arteriovenous malformations (AVMs) who underwent arterial ethanol and N-butyl cyanoacrylate embolization followed by percutaneous cryoablation of residual inaccessible AVMs. After the procedure, minor complications classified as type B according to the Society of Interventional Radiology (SIR) classification system occurred in 75% (3/4) of patients. One patient achieved 90% obliteration of AVM, and 3 patients had complete obliteration of AVM at 1-year follow-up. This reports shows that percutaneous ablation may be a viable treatment option for residual facial AVMs after ethanol and glue embolization. PMID- 27670995 TI - Radiofrequency Ablation for Iatrogenic Thyroid Artery Pseudoaneurysm: Initial Experience. AB - Eight iatrogenic thyroid pseudoaneurysms (ITPAs) after thyroid biopsy are reported. The mean ITPA diameter was 7.2 mm (range 4 to 12 mm). Ultrasound (US) guided compression was initially performed at the neck of the ITPA in all cases. Among them, 4 ITPAs persisted (50%) in which radiofrequency (RF) ablation was performed. Mean RF ablation time and power were 13.5 seconds (range 5 to 24 seconds) and 20 W (range 10 to 50 W), respectively. All 4 cases were treated with RF ablation without any complications. PMID- 27670996 TI - Drill-Assisted Biopsy of the Axial and Appendicular Skeleton: Safety, Technical Success, and Diagnostic Efficacy. AB - The purpose of this study was to evaluate the safety, technical success rate, and diagnostic efficacy of drill-assisted axial and appendicular bone biopsies. During a 3-y period, 703 drill-assisted biopsies were performed. The cohort included 54.2% men, with a mean age of 57.6 y +/- 17.1. Median lesion volume was 10.9 mL (interquartile range, 3.4-30.2 mL). Lesions were lytic (31.7%), sclerotic (21.2%), mixed lytic and sclerotic (27.7%), or normal radiographic bone quality (19.3%). No complications were reported. The technical biopsy success rate was 99.9%. Crush artifact was present in 5.8% of specimens submitted for surgical pathologic examination, and 2.1% of specimens were inadequate for histologic evaluation. PMID- 27670997 TI - Choose Wisely: Choose IR. PMID- 27670998 TI - Reply to: "Biopsy of Paraganglioma and Takotsubo Syndrome". PMID- 27671000 TI - Hur S, Shin JH, Lee IJ, et al. Early Experience in the Management of Postoperative Lymphatic Leakage Using Lipiodol Lymphangiography and Adjunctive Glue Embolization. (J Vasc Interv Radiol 2016;27:1177-1186. PMID- 27670999 TI - Biopsy of Paraganglioma and Takotsubo Syndrome. PMID- 27671001 TI - The platypus in Edinburgh: Robert Jameson, Robert Knox and the place of the Ornithorhynchus in nature, 1821-24. AB - The duck-billed platypus, or Ornithorhynchus, was the subject of an intense debate among natural historians in the late eighteenth and early nineteenth centuries. Its paradoxical mixture of mammalian, avian and reptilian characteristics made it something of a taxonomic conundrum. In the early 1820s Robert Jameson (1774-1854), the professor of natural history at the University of Edinburgh and the curator of the University's natural history museum, was able to acquire three valuable specimens of this species. He passed one of these on to the anatomist Robert Knox (1791-1862), who dissected the animal and presented his results in a series of papers to the Wernerian Natural History Society, which later published them in its Memoirs. This paper takes Jameson's platypus as a case study on how natural history specimens were used to create and contest knowledge of the natural world in the early nineteenth century, at a time when interpretations of the relationships between animal taxa were in a state of flux. It shows how Jameson used his possession of this interesting specimen to provide a valuable opportunity for his protege Knox while also helping to consolidate his own position as a key figure in early nineteenth-century natural history. PMID- 27671003 TI - An electrical analogy to Mie scattering. AB - Mie scattering is an optical phenomenon that appears when electromagnetic waves, in particular light, are elastically scattered at a spherical or cylindrical object. A transfer of this phenomenon onto electron states in ballistic graphene has been proposed theoretically, assuming a well-defined incident wave scattered by a perfectly cylindrical nanometer scaled potential, but experimental fingerprints are lacking. We present an experimental demonstration of an electrical analogue to Mie scattering by using graphene as a conductor, and circular potentials arranged in a square two-dimensional array. The tabletop experiment is carried out under seemingly unfavourable conditions of diffusive transport at room-temperature. Nonetheless, when a canted arrangement of the array with respect to the incident current is chosen, cascaded Mie scattering results robustly in a transverse voltage. Its response on electrostatic gating and variation of potentials convincingly underscores Mie scattering as underlying mechanism. The findings presented here encourage the design of functional electronic metamaterials. PMID- 27671004 TI - PCPNDT seems to benefit India's birth sex ratios. PMID- 27671002 TI - A six-CpG panel with DNA methylation biomarkers predicting treatment response of chemoradiation in esophageal squamous cell carcinoma. AB - BACKGROUND: Prognosis of esophageal squamous cell carcinoma (ESCC) patients remains poor, and the chemoradiotherapy (CRT) applied to ESCC patients often failed. Therefore, development of biomarkers to predict CRT response is immensely important for choosing the best treatment strategy of an individual patient. METHODS: The methylation array and pyrosequencing methylation assay were performed in pre-treatment endoscopic biopsies to identify probes with differential CpG methylation levels between good and poor CRT responders in a cohort of 12 ESCC patients. Receiver operating characteristic curves and multivariate logistic regressions were conducted to build the risk score equation of selected CpG probes in another cohort of 91 ESCC patients to predict CRT response. Kaplan-Meier analysis was used to estimate progression-free survival or time-to-progression of patients predicted with good and poor CRT responses. RESULTS: Nine differentially methylated CpG probes were identified to be associated with CRT response. A risk score equation comprising six CpG probes located in IFNGR2, KCNK4, NOTCH4, NPY, PAX6, and SOX17 genes were built. The risk score was derived from the sum of each probe multiplied by its corresponding coefficient. Such a risk score has a good prediction performance in discriminating poor CRT responders from good responders (AUC: 0.930). Moreover, poor CRT responders predicted by risk score significantly had poorer prognosis in terms of shorter progression-free survival and time-to-progression (p = 0.004 0.008). CONCLUSION: We established a proof-of-concept CRT response prediction panel consisting of six-CpG methylation biomarkers in identifying ESCC patients who are at high risk of CRT failure and need intensive care. PMID- 27671005 TI - Surgical revision of benign hepaticojejunostomy stricture using a robotic system (with video). PMID- 27671006 TI - Improvement of peri-operative patient management to enable outpatient colectomy. AB - AIM OF THE STUDY: Outpatient left colectomy has been described in several small series or case reports. We conducted a prospective study to determine whether an optimized management approach could allow performance of this procedure in a broader patient population. PATIENTS AND METHODS: Between December 2014 and December 2015, all eligible patients were prospectively and consecutively included in this study. They all underwent surgery following the same outpatient management protocol. After discharge, patients were followed by home health nurses with surgeon follow-up visits on days 10 and 21 (D10, D21) or earlier, if necessary. RESULTS: During this period, 56 patients underwent a left colectomy, 47 of whom met the inclusion criteria. Seven patients refused the outpatient care approach, leaving a total of 40 patients included (8 ASA 3 [American Society of Anesthesiologists], 24 ASA 2, 8 ASA 1). All but one of the patients were able to return home the same evening. Bowel motility was restored on D1 for most patients. Two patients had abdominal pain that required a follow-up visit before D10 but their subsequent course was uneventful. No patient was re-hospitalized. An uncomplicated post-operative course was confirmed at follow-up visits on D10 and D21. CONCLUSION: Our study confirms that outpatient left colectomy is feasible for most patients, including fragile patients and/or those undergoing more complex procedures. Communication and close coordination by all stakeholders as well AS optimal organization of downstream patient care are essential to guarantee quality and safety. PMID- 27671007 TI - Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences. AB - The aim of the NeoVitaA Trial is to assess the role of postnatal additional high dose oral vitamin A supplementation for 28 days in reducing Bronchopulmonary dysplasia (BPD) or death in extremely low birth weight (ELBW) infants at 36 weeks postmenstrual age (PMA). All infants (both intervention and control group) will be provided with basic vitamin A (1000 IU/kg/day) in addition to trial intervention.In this short communication, we will give an up-date on obstacles, challenges as well as perspectives and potential solutions when putting into place a multicenter, double-blind, randomized trial in this cohort of extremely susceptible infants. PMID- 27671009 TI - Efficient boron abstraction using honeycomb-like porous magnetic hybrids: Assessment of techno-economic recovery of boric acid. AB - Porous magnetic hybrids were synthesized and functionalized with glycidol to produce boron-selective adsorbent. The magnetic hybrid (MH) comparatively out performed the existing expensive adsorbents. MH had a saturation magnetisation of 63.48 emu/g and average pore diameter ranging from meso to macropores. The magnetic hybrids showed excellent selectivity towards boron and resulted in 79 93% boron removal even in the presence of competing metal ions (Na+ and Cr2+). Experiments were performed in a column system, and breakthrough time was observed to increase with bed depths and decreased with flow rates. The batch experiments revealed that 60 min was enough to achieve equilibrium, and the level of boron sorption was 108.5 mg/g from a synthetic solution. Several adsorption-desorption cycles were performed using a simple acid-water treatment and evaluated using various kinetic models. The spent adsorbents could be separated easily from the mixture by an external magnetic field. The cost-benefit analysis was performed for the treatment of 72 m3/year boron effluent, including five years straight line depreciation charges of equipment. The net profit and standard percentage confirmed that the recovery process is economically feasible. PMID- 27671008 TI - Autoimmune gastritis. AB - Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis. PMID- 27671010 TI - Desmoteplase for Acute Ischemic Stroke within 3 to 9 Hours after Symptom Onset: Evidence from Randomized Controlled Trials. AB - Recent studies have shown inconsistent results regarding the value of desmoteplase for treating acute ischemic stroke (AIS) when administered within an extended time window. We performed a meta-analysis to explore the value of desmoteplase in AIS treatment. The MEDLINE, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that had evaluated desmoteplase versus placebo for AIS. The primary outcomes were intracranial hemorrhage (ICH) within 72 hours and favorable outcome at Day 90. We pooled 819 patients from 5 RCTs. Desmoteplase treatment showed a neutral effect on favorable outcome (P = 0.42) but a favorable safety profile in terms of ICH (P = 0.64) compared with the placebo group. In the subgroup analysis, 90 MUg/kg desmoteplase, a late time to treatment (6-9 hours), and serious stroke symptoms at baseline (NIHSS > 12) subgroups showed high risks of ICH (P <= 0.02). A high dose of desmoteplase (125 MUg/kg) showed a tendency to improve recanalization (P = 0.05), but was also associated with an increased risk of death (P = 0.04). In conclusion, desmoteplase administered over an extended time window had no significant effect on functional recovery but exhibited a favorable safety profile in patients with AIS. PMID- 27671011 TI - Highly Twisted Dianchoring D-pi-A Sensitizers for Efficient Dye-Sensitized Solar Cells. AB - Two new organic dyes-BPDTA and BTTA-possessing dual D-pi-A units have been synthesized, characterized, and employed as efficient sensitizers for dye sensitized solar cells. The two individual D-pi-A, which are based on (E)-3-(5' (4-(bis(4-(hexyloxy)phenyl)amino)phenyl)-[2,2'-bithiophen]-5-yl)-2-cyanoacrylic acid unit (D21L6), are connected directly between phenylene or thiophene within linear pi-conjugated backbone to constitute a highly twisted architecture for suppressing the dye aggregation. The new dianchoring dyes exhibited pronounced absorption profile with higher molar extinction coefficient, which is consistent with the results obtained from density functional theory (DFT) calculations. The theoretical analysis also indicated that the charge transfer transition is mainly constituted of HOMO/HOMO-1 to LUMO/LUMO+1 that were found to be located on donor and acceptor segments, respectively. Theoretical calculations give the distance between two binding sites of 19.50 A for BPDTA and 12.04 A for BTTA. The proximity between two anchoring units of BTTA results in superior dye loading and, hence, higher cell efficiency. The BTTA-based device yielded an optimized efficiency of 6.86%, compared to 6.61% for the BPDTA-based device, whereas the model sensitizer D21L6 only delivered an inferior performance of 5.33% under similar conditions. Our molecular design strategy thus opens up a new horizon to establish efficient dianchoring dyes. PMID- 27671012 TI - Repeat caesarean: time to re-evaluate the current practice. PMID- 27671013 TI - The SaTH risk-assessment tool for the prediction of emergency cesarean section in women having induction of labor for all indications: a large-cohort based study. AB - PURPOSE: To develop a risk-assessment model for the prediction of emergency cesarean section (CS) in women having induction of labor (IOL). METHODS: This was an observational cohort study of women with IOL for any indication between 2007 and 2013. Women induced for stillbirths and with multiple pregnancies were excluded. The primary objective was to identify risk factors associated with CS delivery and to construct a risk-prediction tool. RESULTS: 6169 women were identified with mean age of 28.9 years. Primiparity involved 47.1 %, CS rate was 13.3 % and post-date pregnancies were 32.4 %. Risk factors for CS were: age >30 years, BMI >25 kg/m2, primiparity, black-ethnicity, non post-date pregnancy, meconium-stained liquor, epidural analgesia, and male fetal gender. Each factor was assigned a score and with increasing scores the CS rate increased. The CS rate was 5.4 % for a score <11, while for a score >=11 it increased to 25.0 %. The model had a sensitivity, specificity, negative predictive value and positive predictive value of 75.8, 65.1, 93.8 and 25.0 %, respectively. CONCLUSION: We have constructed a risk-prediction tool for CS delivery in women with IOL. The risk-assessment tool for the prediction of emergency CS in induced labor has a high negative-predictive value and can provide reassurance to presumed low-risk women. PMID- 27671015 TI - Role of Arsenic During Aluminum Droplet Etching of Nanoholes in AlGaAs. AB - Self-assembled nanoholes are drilled into (001) AlGaAs surfaces during molecular beam epitaxy (MBE) using local droplet etching (LDE) with Al droplets. It is known that this process requires a small amount of background arsenic for droplet material removal. The present work demonstrates that the As background can be supplied by both a small As flux to the surface as well as by the topmost As layer in an As-terminated surface reconstruction acting as a reservoir. We study the temperature-dependent evaporation of the As topmost layer with in situ electron diffraction and determine an activation energy of 2.49 eV. After thermal removal of the As topmost layer droplet etching is studied under well-defined As supply. We observe with decreasing As flux four regimes: planar growth, uniform nanoholes, non-uniform holes, and droplet conservation. The influence of the As supply is discussed quantitatively on the basis of a kinetic rate model. PMID- 27671014 TI - Single-Incision and Natural Orifice Translumenal Endoscopic Surgery in Switzerland. AB - BACKGROUND: Single-incision laparoscopy (SIL) and natural orifice translumenal endoscopic surgery (NOTES) aim at reducing surgical access trauma. To monitor the introduction of emerging technologies, the Swiss Association for Laparo- and Thoracoscopic Surgeons launched a database in 2010. The current status of SIL and NOTES in Switzerland is reported, and the techniques are compared. METHODS: The number and type of procedures, surgeon experience, their impressions of performance, conversion, and complications between 2010 and 2015 are described. A survey was used to acquire additional data not included in the registry. RESULTS: Nine centers included 650 procedures. Cholecystectomy (55 %) and sigmoidectomy (26 %) were most prevalent in both techniques. The number of active centers declined from 9 to 2 during the study period. The frequencies of taught procedures were 4 and 43 % for SIL and NOTES (p < 0.001), and surgeon self estimated impression of performance was perfect in 50 and 89 %, respectively (p < 0.0001). Conversions in total were 3.6 and 5.7 %, respectively, and 1.1 % to open for both techniques. Morbidity was 5 % in SIL and 2.7 % in NOTES, with 0.8 % access-related complications in NOTES and none in SIL (p = 0.29). Of laparoscopic cholecystectomy, sigmoidectomy, and right hemicolectomy, 11.4 and 15.6 % of cases were operated using SIL or NOTES, respectively (p < 0.0001). CONCLUSIONS: Although in selected specialized centers, a considerable proportion of patients were treated using novel techniques, a fading interest of the surgical community in SIL and NOTES was observed. The proportion of SIL and NOTES procedures taught is insufficient and calls for improvement. PMID- 27671017 TI - Influence of Nanopore Shapes on Thermal Conductivity of Two-Dimensional Nanoporous Material. AB - The influence of nanopore shapes on the electronic thermal conductivity (ETC) was studied in this paper. It turns out that with same porosity, the ETC will be quite different for different nanopore shapes, caused by the different channel width for different nanopore shapes. With same channel width, the influence of different nanopore shapes can be approximately omitted if the nanopore is small enough (smaller than 0.5 times EMFP in this paper). The ETC anisotropy was discovered for triangle nanopores at a large porosity with a large nanopore size, while there is a similar ETC for small pore size. It confirmed that the structure difference for small pore size may not be seen by electrons in their moving. PMID- 27671016 TI - Size effect of Au/PAMAM contrast agent on CT imaging of reticuloendothelial system and tumor tissue. AB - Polyamidoamine (PAMAM)-entrapped Au nanoparticles were synthesized with distinct sizes to figure out the size effect of Au-based contrast agent on CT imaging of passively targeted tissues. Au/PAMAM nanoparticles were first synthesized with narrow distribution of particles size of 22.2 +/- 3.1, 54.2 +/- 3.7, and 104.9 +/ 4.7 nm in diameters. Size effect leads no significant difference on X-ray attenuation when Au/PAMAM was <=0.05 mol/L. For CT imaging of a tumor model, small Au/PAMAM were more easily internalized via endocytosis in the liver, leading to more obviously enhanced contrast. Similarly, contrast agents with small sizes were more effective in tumor imaging because of the enhanced permeability and retention effect. Overall, the particle size of Au/PAMAM heavily affected the efficiency of CT enhancement in imaging RES and tumors. PMID- 27671018 TI - Analyses of prognosis-related factors of intracranial solitary fibrous tumors and hemangiopericytomas help understand the relationship between the two sorts of tumors. AB - Increasing evidence has suggested a close relationship between solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) in the central nervous system (CNS). However, CNS SFTs differentiate from HPCs in their clinical behavior and patient prognoses. Analyses of prognosis-related factors can help clarify the relationship between SFT and HPC. The intracranial SFT and HPC cases treated in our departments from January 2002 to December 2012 were retrospectively reviewed. The SFT and HPC cases were also combined into an SFT/HPC group. The factors associated with patient progression-free survival (PFS) and overall survival (OS) were statistically analyzed using uni- and multivariate analyses. Fifty-eight intracranial SFT/HPC patients including 38 SFT patients and 20 HPC patients were treated during this period. The "Marseille grading" evaluated upon the histological aggressive phenotypes was applied in this study. The grading reflected a malignant progression ranging from "conventional" SFTs (grade I) to WHO III HPCs (grade III), and grade was negatively correlated with the PFS and OS of the SFT, HPC and SFT/HPC patients (P < 0.05).The multivariate analyses revealed that gross total resection (GTR) was significantly positively correlated with PFS and OS in the SFT, HPC and SFT/HPC patients and that radiotherapy was significantly positively correlated with PFS in the HPC and SFT/HPC patients (P < 0.05). In conclusion, the intracranial SFTs and HPCs share common prognostic factors including extent of surgery and pathology, moreover, the histological grading of the aggressive phenotypes supports the unifying of the CNS SFT and HPC into one tumor entity of SFT/HPC. PMID- 27671019 TI - Quaternized chitosan/kappa-carrageenan/caffeic acid-coated poly(3 hydroxybutyrate) fibrous materials: Preparation, antibacterial and antioxidant activity. AB - Novel fibrous materials with antioxidant and antibacterial properties from poly(3 hydroxybutyrate) (PHB), quaternized chitosan (QCh), kappa-carrageenan (Car) and caffeic acid (CA) were obtained. These materials were prepared by applying electrospinning or electrospinning in conjunction with dip-coating and polyelectrolyte complex (PEC) formation. It was found that the CA release depended on the fiber composition. X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) revealed that CA incorporated in the fibers was in the amorphous state, whereas CA included in the coating was in the crystalline state. In contrast to the neat PHB mats, the CA-containing mats and the PEC QCh/Car-coated mats were found to kill the Gram-positive bacteria S. aureus and the Gram-negative bacteria E. coli and were effective in suppressing the adhesion of pathogenic bacteria S. aureus. Enhancement of the antioxidant activity of the fibrous materials containing both CA and QCh/Car coating was observed. PMID- 27671020 TI - Do Commonly Used Functional Outcome Measures Capture Activities that Are Relevant for People with Stroke in India? AB - OBJECTIVES: In India, post-stroke outcomes are determined using functional outcome measures (FOMs), the contents of which have not been validated for their relevance to the Indian population. In this study, we aimed to evaluate the cultural validity of five frequently used stroke-specific FOMs by comparing their contents with the problems reported by patients with stroke in India. METHODS: Face-to-face structured interviews were conducted with 152 patients diagnosed with stroke in India. Problems and goals identified by the patients were compared to each item included in the FOMs used in stroke rehabilitation. RESULTS: The Stroke Impact Scale (SIS) and the Frenchay Activities Index (FAI) include items related to the most frequently identified problems. However, neither covers problems related to the need for squatting and sitting on the floor. Use of public transport and community walking are not included in the SIS. Leisure and recreational activities (e.g. gardening, reading books), cognitive and speech functions (e.g. memory, thinking) and bowel and bladder dysfunctions were the common items identified as "not a problem" or "not relevant" by the patients. DISCUSSION: Our findings suggest that the SIS and FAI are the most appropriate FOMs for patients with stroke in India as they include items related to the majority of problems identified by study participants. Many items on both measures, however, were identified as not a problem or not relevant. There is a need for developing culture-specific FOMs that incorporate all major concerns expressed by patients with stroke in India. PMID- 27671021 TI - Which unscheduled return visits indicate a quality-of-care issue? AB - BACKGROUND: The rate of unscheduled return visits is often used as a quality-of care indicator in EDs, although its validity is not yet fully established. Our aim was to identify the characteristics of return visits that may be attributed to problems in quality of care. METHODS: Retrospective paired review of medical charts in a random sample of return visits during the 72 hours following discharge from the ED in three hospitals of Andalusia, Spain in 2013. Charts were reviewed by senior medical physicians to determine which return visits reflected quality-of-care problems. Time frame for return visit, index and return visit acuity, disposition and diagnosis were compared with determine which variables were associated with a quality problem. Sensitivity and specificity for each variable to indicate a quality problem were determined. RESULTS: We studied the causes of 895 return visits, finding that 65 (7.3%) were due to inadequate quality of care in the index visit. Potentially avoidable return visits were more common in more severely ill patients, in those with greater severity in the return than in the index visit and in patients hospitalised after the return. The combination of this three variables presented sensitivity 66% and specificity 68% in identification of quality-related returns. CONCLUSIONS: The overall level of return visits cannot be considered a valid indicator of quality of care. However, certain specific variables, including the level of severity of the patient's condition or the discharge destination following the return visits, could be considered valid in this respect. PMID- 27671022 TI - Prevalence of and Factors Associated With Multidrug Resistant Organism (MDRO) Colonization in 3 Nursing Homes. AB - Nursing home residents are at risk for acquiring and transmitting MDROs. A serial point-prevalence study of 605 residents in 3 facilities using random sampling found MDRO colonization in 45% of residents: methicillin-resistant Staphylococcus aureus (MRSA, 26%); extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL, 17%); vancomycin-resistant Enterococcus spp. (VRE, 16%); carbapenem resistant Enterobacteriaceae (CRE, 1%). MDRO colonization was associated with history of MDRO, care needs, incontinence, and catheters. Infect Control Hosp Epidemiol 2016;1485-1488. PMID- 27671024 TI - Bench to bedside advances in the 21st century for primary headache disorders: migraine treatments for migraine patients. PMID- 27671025 TI - Short-lasting unilateral neuralgiform headache attacks: where is the headache generator? PMID- 27671023 TI - Characterization of new transposable element sub-families from white clover (Trifolium repens) using PCR amplification. AB - Transposable elements (TEs) dominate the landscapes of most plant and animal genomes. Once considered junk DNA and genetic parasites, these interspersed, repetitive DNA elements are now known to play major roles in both genetic and epigenetic processes that sponsor genome variation and regulate gene expression. Knowledge of TE consensus sequences from elements in species whose genomes have not been sequenced is limited, and the individual TEs that are encountered in clones or short-reads rarely represent potentially canonical, let alone, functional representatives. In this study, we queried the Repbase database with eight BAC clones from white clover (Trifolium repens), identified a large number of candidate TEs, and used polymerase chain reaction and Sanger sequencing to create consensus sequences for three new TE families. The results show that TE family consensus sequences can be obtained experimentally in species for which just a single, full-length member of a TE family has been sequenced. PMID- 27671027 TI - Targeting tubers in paediatric epilepsy surgery candidates. PMID- 27671026 TI - Memory in autoimmune NMDA receptor encephalitis: an issue for B cells and patients. PMID- 27671028 TI - Does BDNF Val66Met contribute to preclinical Alzheimer's disease? PMID- 27671029 TI - A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia. AB - As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter * interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection * lifetime) and Patient 1 (joint incubation and age at infection * 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia. PMID- 27671030 TI - Assessment of sexual difficulties associated with multi-modal treatment for cervical or endometrial cancer: A systematic review of measurement instruments. AB - BACKGROUND: Practitioners and researchers require an outcome measure that accurately identifies the range of common treatment-induced changes in sexual function and well-being experienced by women after cervical or endometrial cancer. This systematic review critically appraised the measurement properties and clinical utility of instruments validated for the measurement of female sexual dysfunction (FSD) in this clinical population. METHODS: A bibliographic database search for questionnaire development or validation papers was completed and methodological quality and measurement properties of selected studies rated using the Consensus-based Standards for the selection of health Measurement Instrument (COSMIN) checklist. RESULTS: 738 articles were screened, 13 articles retrieved for full text assessment and 7 studies excluded, resulting in evaluation of 6 papers; 2 QoL and 4 female sexual morbidity measures. Five of the six instruments omitted one or more dimension of female sexual function and only one instrument explicitly measured distress associated with sexual changes as per DSM V (APA 2013) diagnostic criteria. None of the papers reported measurement error, responsiveness data was available for only two instruments, three papers failed to report on criterion validity, and test-retest reliability reporting was inconsistent. Heterosexual penile-vaginal intercourse remains the dominant sexual activity focus for sexual morbidity PROMS terminology and instruments lack explicit reference to solo or non-coital sexual expression or validation in a non heterosexual sample. Four out of six instruments included mediating treatment or illness items such as vaginal changes, menopause or altered body image. CONCLUSIONS: Findings suggest that the Female Sexual Function Index (FSFI) remains the most robust sexual morbidity outcome measure, for research or clinical use, in sexually active women treated for cervical or endometrial cancer. Development of an instrument that measures sexual dysfunction in women who are infrequently/not sexually active due to treatment consequences is still required to identify women in need of sexual rehabilitation. PMID- 27671031 TI - Immediate and mediate furcal perforation treatment in primary molars: 24-month follow-up. AB - BACKGROUND: Furcal perforation consists of a communication between the pulp cavity and the periodontal tissues that can occur accidentally during cavity preparation or root canal instrumentation. This complication may lead to inflammatory reactions and compromise adjacent tissues irreversibly, resulting in the early loss of primary teeth. Perforation sealing with a biocompatible material is necessary to ensure a favourable prognosis. Among different materials, MTA has been employed due to its excellent healing and physical properties. CASE REPORT: The purpose of these case reports was to describe immediate and mediate cases of furcal perforation treatment using MTA in primary molars. In both the cases, after accidental perforation detection, the pulp chamber was cleaned with saline solution to clear off the debris. The wound surface was continuously irrigated with saline solution and a dry sterile cotton pellet was placed on the radicular pulp stumps and perforation area with slight pressure until the bleeding was controlled. The MTA was applied into the perforation and pulp chamber area with the aid of a sterile amalgam carrier. The teeth were restored with resin-modified glass ionomer cement. FOLLOW-UP: Clinical and radiographic follow-up examinations were carried out at 3, 6, 12, 18, and 24 months after perforation sealing. Both the cases remained asymptomatic, presenting no discomfort, mobility, swelling, or fistula after 24-months follow up. Radiographically, the radiolucent area disappeared as a result of bone formation in the inter-radicular space, showing adjacent tissue preservation. CONCLUSION: Thus, MTA may be considered as an ideal option for conservative treatment of immediate and mediate furcal perforation in primary teeth, once it promoted repair with tooth maintenance in both the cases. PMID- 27671032 TI - Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients. AB - BACKGROUND: The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial. METHODS: A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR). RESULTS: Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06). CONCLUSIONS: SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population. PMID- 27671033 TI - What people know about congenital CMV: an analysis of a large heterogeneous population through a web-based survey. AB - BACKGROUND: Congenital CMV (cCMV) infection is a serious public health issue due to both its worldwide prevalence and the severe and permanent impairments it causes. However, awareness of this infection is low in the general population and among pregnant women, and it also seems to be generally disregarded by healthcare providers. The identification of factors behind this inadequate level of knowledge could provide a basis for future preventive measures. This study aimed at evaluating awareness of CMV and cCMV infection and its correlation with socio demographic variables in a general population. METHODS: The survey was carried out by computer-assisted web interviewing (CAWI). A questionnaire was sent via e mail to the 70,975 individuals who comprised the whole population (students, administrative staff, teaching staff) of Milan University, Italy in 2015. RESULTS: Out of the 10,190 respondents, 5,351 (52.5 %) had already heard of CMV but only 3,216 (31.8 %) knew that this virus could be implicated in congenital infection. Urine and breastfeeding were the least recognized transmission routes for CMV infection; less than half of respondents accurately identified the right symptoms and sequelae caused by cCMV infection. The correct hygienic measures against cCMV infection were identified in percentages ranging from 55.6 to 75 % depending on the measures proposed but about one in three of interviewees deemed those measures unnecessary in the event of a pregnant woman already being CMV seropositive. From the mean knowledge scores the most complete quality of awareness of CMV turned out to be linked to childbearing-age (25-40 year) and with not having children, even if results for non-parents showed less of them having heard of cCMV than parents. CONCLUSION: Our results indicate a limited and confused awareness of cCMV infection in a large, fairly young and well-educated Italian population. PMID- 27671034 TI - The association between weight perception and BMI: report and measurement data from the growing up in Ireland Cohort Study of 9-year olds. AB - BACKGROUND: The gold standard for categorisation of weight status is clinically measured body mass index (BMI), but this is often not practical in large epidemiological studies. OBJECTIVES: To determine if a child's weight perception or a mother's perception of a child's weight status is a viable alternative to measured height and weight in determining BMI classification. Secondary outcomes are to determine the influence of a mother's BMI on her ability to categorise the child's BMI and a child's ability to recognise his/her own BMI. METHODS: Cross sectional analysis of the growing up in Ireland cohort study, a nationally representative cohort of 8568 9-year-old children. The variables considered for this analysis are the child's gender, BMI (International Obesity Taskforce grade derived from measured height and weight) and self-perceived weight status, and the mother's weight perception of the child, BMI (derived from measured height and weight) and self-perceived weight status. Cohen's weighted-kappa was used to evaluate the strength of the agreement between pairwise combinations of the BMI variables. Cumulative and adjacent categories logistic regression were used to predict how likely a person rates themselves as under, normal or overweight, based on explanatory variables. RESULTS: Mothers are more accurate at correctly classifying their child's BMI (kappa=0.5; confidence intervals (CI) 0.38-0.51) than the children themselves (kappa=0.25; CI 0.23-0.26). Overweight mothers are better raters of their child's BMI (kappa=0.51; CI 0.49-0.54), compared with normal (kappa=0.44; CI 0.41-0.47) or underweight mothers (kappa=0.4; CI 0.22 0.58), regardless of whether the mother's BMI is derived from measured height and weight or self-perceived. The mother's perception of the child's weight status is not an influencing factor on the child's ability to correctly classify him/herself, but the child's self-perceived weight status influences the mother's ability to correctly classify the child. CONCLUSIONS: A mother's BMI classification of her child is a viable alternative to BMI measurement in large epidemiological studies. PMID- 27671035 TI - Modelling obesity trends in Australia: unravelling the past and predicting the future. AB - BACKGROUND/OBJECTIVES: Modelling is increasingly being used to predict the epidemiology of obesity progression and its consequences. The aims of this study were: (a) to present and validate a model for prediction of obesity among Australian adults and (b) to use the model to project the prevalence of obesity and severe obesity by 2025. SUBJECTS/METHODS: Individual level simulation combined with survey estimation techniques to model changing population body mass index (BMI) distribution over time. The model input population was derived from a nationally representative survey in 1995, representing over 12 million adults. Simulations were run for 30 years. The model was validated retrospectively and then used to predict obesity and severe obesity by 2025 among different aged cohorts and at a whole population level. RESULTS: The changing BMI distribution over time was well predicted by the model and projected prevalence of weight status groups agreed with population level data in 2008, 2012 and 2014.The model predicts more growth in obesity among younger than older adult cohorts. Projections at a whole population level, were that healthy weight will decline, overweight will remain steady, but obesity and severe obesity prevalence will continue to increase beyond 2016. Adult obesity prevalence was projected to increase from 19% in 1995 to 35% by 2025. Severe obesity (BMI>35), which was only around 5% in 1995, was projected to be 13% by 2025, two to three times the 1995 levels. CONCLUSIONS: The projected rise in obesity severe obesity will have more substantial cost and healthcare system implications than in previous decades. Having a robust epidemiological model is key to predicting these long-term costs and health outcomes into the future. PMID- 27671036 TI - Validation of NOViSE. AB - The goal of this study was to establish face, content, and construct validity of NOViSE-the first force-feedback enabled virtual reality (VR) simulator for natural orifice transluminal endoscopic surgery (NOTES). Fourteen surgeons and surgical trainees performed 3 simulated hybrid transgastric cholecystectomies using a flexible endoscope on NOViSE. Four of them were classified as "NOTES experts" who had independently performed 10 or more simulated or human NOTES procedures. Seven participants were classified as "Novices" and 3 as "Gastroenterologists" with no or minimal NOTES experience. A standardized 5-point Likert-type scale questionnaire was administered to assess the face and content validity. NOViSE showed good overall face and content validity. In 14 out of 15 statements pertaining to face validity (graphical appearance, endoscope and tissue behavior, overall realism), >=50% of responses were "agree" or "strongly agree." In terms of content validity, 85.7% of participants agreed or strongly agreed that NOViSE is a useful training tool for NOTES and 71.4% that they would recommend it to others. Construct validity was established by comparing a number of performance metrics such as task completion times, path lengths, applied forces, and so on. NOViSE demonstrated early signs of construct validity. Experts were faster and used a shorter endoscopic path length than novices in all but one task. The results indicate that NOViSE authentically recreates a transgastric hybrid cholecystectomy and sets promising foundations for the further development of a VR training curriculum for NOTES without compromising patient safety or requiring expensive animal facilities. PMID- 27671038 TI - Melanoma and obesity: Should antioxidant vitamins be addressed? AB - Melanoma is an aggressive form of skin cancer refractory to conventional therapies. Obesity has reached epidemic dimensions acting as a risk factor for several cancer types, such as melanoma. Several reactive species of oxygen are also involved in melanoma initiation and progression. Low levels of antioxidant content and/or activity in lightly pigmented cells could expose them to an extremely oxidative environment and rise the susceptibility to oxidative damage and consequently loss of cell homeostasis. Despite the knowledge about melanoma biology, pathogenesis and developed therapies, is extremely important to understand the antioxidant modulation of melanoma under an environment of obesity, especially the effect of some natural compounds of the diet, such as antioxidant vitamins A, C and E and selenium in order to establish alternatives to conventional therapies, which are known to be ineffective against melanoma. PMID- 27671037 TI - Assessing outcomes of enhanced chronic disease care through patient education and a value-based formulary study (ACCESS)-study protocol for a 2*2 factorial randomized trial. AB - BACKGROUND: Chronic diseases result in significant morbidity and costs. Although medications and lifestyle changes are effective for improving outcomes in chronic diseases, many patients do not receive these treatments, in part because of financial barriers, patient and provider-level knowledge gaps, and low patient motivation. The Assessing outcomes of enhanced chronic disease care through patient education and a value-based formulary study (ACCESS) will determine the impact of two interventions: (1) a value-based formulary which eliminates copayment for high-value preventive medications; and (2) a comprehensive self management support program aimed at promoting health behavior change and medication adherence, combined with relay of information on medication use to healthcare providers, on cardiovascular events and/or mortality in low-income seniors with elevated cardiovascular risk. METHODS: The ACCESS study will use a parallel, open label, factorial randomized trial design, with blinded endpoint evaluation in 4714 participants who are over age >65 (and therefore have drug insurance provided by Alberta Blue Cross with 30 % co-payment); are at a high risk for cardiovascular events based on a history of any one of the following: coronary heart disease, prior stroke, chronic kidney disease, heart failure, or any two of the following: current cigarette smoking, diabetes mellitus, hypertension, or hypercholesterolemia; and have a household income 12 months after placement, abdominal pain and body weight increasing >=5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P> 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects. PMID- 27671046 TI - [Standardization of colposcopic terminology and its significance]. PMID- 27671047 TI - [Study on the dynamic changes of D-dimer during pregnancy and early puerperium]. AB - Objective: To explore the dynamic changes of D-dimers during pregnancy and early puerperium(within 3 days postpartum). Methods: A retrospective study was performed among 8 367 healthy women who had term singleton delivery in Women's Hospital, School of Medicine, Zhejiang University from January 2007 to December 2014. D-dimers concentrations during pregnancy and early puerprium of all the cases were collected. Data of 21 065 D-dimers tests were assigned to 5 groups according to the time of sampling, including early pregnancy(<=12 gestation weeks), middle pregnancy(12-28 gestation weeks), late pregnancy(>28 gestation weeks), 1 postpartum(within 48 hours postpartum)and 2 postpartum(48- 72 hours postpartum). The D-dimers concentrations in different groups were compared. The effect of delivery mode on D-dimers of early pureperium was analyzed. The correlation between D-dimers and the thromboembolic disease was also explored. In this study, Student's t-test and Wilcoxon rank sum test were used for statistical analysis. D-dimers concentration <=0.5 mg/L was used as the normal range. Results: (1)D-dimers concentrations during pregnancy were higher than the non pregnant women(P<0.01), but there was no statistical difference between early pregnancy and late pregnancy(P=0.820). D-dimers concentration in the 1 postpartum group was higher than that of early pregnancy group or late pregnancy group(P<0.01). But in the 2 postpartum group, it was lower than early pregnancy, late pregnancy and 1 postpartum groups.(2)D-dimers in cesarean section cases was significantly higher than in vaginal delivery cases in each period of pregnancy and early pueprium.(3)The 95%CI of D-dimers in early pregnancy, late pregnancy, 48 hours after vaginal delivery, 48- 72 hours after vaginal delivery, <=48 hours after cesarean section, 48- 72 hours after cesarean section were 0.58-8.28, 0.47 11.52, 1.04-9.59, 0.87-5.22, 1.07-11.58 and 1.00-6.23 mg/L, respectively.(4)In 6 cases with thromboembolic disease, D-dimers was 6.89- 19.89 mg/L, with the mean value of 13.66 mg/L. It was significantly higher than normal range. In 3 cases, all after cesarean section, with lower extremity vein thrombosis within 48 hours postpartum, the D-dimers concentrations, 9.77, 8.65 and 6.89 mg/L respectively, were in the 95% CI of the study population after cesarean section. Conclusions: D dimers concentration of 0.5 mg/L is not suitable for venous thromboembolism screening during pregnancy. D-dimers concentration in pregnancy and early puerprium is higher than non-pregnancy. It increases in the very early period postpartum and decreases with time. D-dimers should not be a routine screening test to exclude thromboembolic disease in pregnant women without high risk factors and clinical manifestation of thromboembolic disease. PMID- 27671048 TI - [Application of temporary balloon occlusion of the abdominal aorta in the treatment of complete placenta previa complicated with placenta accreta]. AB - Objective: To investigate the value of temporary balloon occlusion of the abdominal aorta in the treatment of complete placenta previa with placenta accreta. Methods: From January 2015 to February 2016, 24 cases of complete placenta previa with placenta accreta were treated with temporary balloon occlusion of the abdominal aorta(the study group)before cesarean, and 24 cases of complete placenta previa with placenta accreta did not receive balloon occlusion(the control group). The operation time, intraoperative blood loss, intraoperative blood transfusion volume, the perioperative hemoglobin level, the hysterectomy rate and the related complications were compared retrospectively.Also, the hospitalization time, the blood coagulation parameters after operation, including activated partial thromboplastin time(APTT), fibrinogen(FIB), D-Dimer and reperfusion injury parameters including creatine phosphokinase(CK), creatine phosphokinase isoenzyme(CK-MB), lactate dehydrogenase(LDH)and serum creatinine were compared between the 2 groups. Results: The blood loss[750 ml(400- 2 000 ml)vs 2 000 ml(1 500- 2 375 ml); Z= 3.214, P=0.001]and blood transfusion volume[200 ml(0-800 ml)vs 800 ml(0-1 200 ml); Z=- 2.173, P=0.030]in the study group were lower than in the control group. The hemoglobin difference between before and after operation in the study group was lower than the control group[(12.8+/-13.4)g/L vs(22.9+/-20.1)g/L; t=-2.041, P=0.047]. In the study group, there were still bleeding in 13 cases after releasing the balloon, 5 of them received uterine artery embolization, 5 cases received uterine artery ligation, and 3 cases received uterine packing. One case had venous thrombosis in the right lower limb. Two cases(8%,2/24)in the control group had hysterectomy, while none in the study group, there was no statistical significance(P= 0.489). Conclusions: Temporary balloon occlusion of the abdominal aorta can effectively reduce blood loss and blood transfusion in the treatment of complete placenta previa with placenta accreta, but there is still the risk of continuing bleeding after releasing the balloon. Other methods of hemostasis might be needed. PMID- 27671049 TI - [Expression and significance of EPCR in plasma and placenta of patients with early onset severe preeclampsia]. AB - Objective: To investigate the expression of endothelial protein C receptor(EPCR)and its roles in plasma and placenta of patients with early onset severe preeclampsia. Methods: Sixty cases of severe preeclampsia women who delivered in Xuzhou Maternity and Child Health Care Hospital from March 2014 to February 2016, were recruited, which included 30 cases with early onset severe preeclampsia(early onset group, gestational week <34 weeks)and 30 patients with late onset severe preeclampsia(late onset group, gestational week >=34 weeks). Thirty cases of healthy late pregnant women at the same period(gestational week >=34 weeks)were selected as control group. Immunohistochemistry SP method was applied to detect the expression of in EPCR placenta. Reverse transcription(RT)- PCR was used to detect the expression of EPCR mRNA in placenta. ELISA method was used to detect the levels of soluble EPCR(sEPCR)level in plasma of the pregnant women of the three groups. Results: The expression of EPCR in placenta mainly distributed in the membrane and cytoplasm of placental syncytiotrophoblasts and vascular endothelial cells, a few in the cell nucleus. The expression of EPCR in early onset group(57%, 17/30)was significantly lower than that in late onset group(93%, 28/30; chi2=25.165, P=0.001). The expression of EPCR in late onset group had no significant difference from that in control group(97%, 29/30; chi2=0.540, P= 0.910). The expression of EPCR mRNA in placenta of early onset group(0.40+/-0.07)was significantly lower than that in late onset group(0.91+/ 0.06; t=-30.044, P=0.001), while there was no statistical difference of the expression of EPCR mRNA between the late onset group and the control group(0.92+/ 0.07; t=-0.631, P=0.538). Plasma sEPCR level in early onset group, late onset group and control group were(231 +/- 11),(124+/-6)and(121+/-4)MUg/L respectively, which is higher in early onset group than that in late onset group(t=48.080, P=0.001). There was no statistical difference of plasma sEPCR level between the late onset group and the control group(t=2.534, P=0.100). Conclusions: The pathogenesis of early onset and late onset severe preeclampsia may be different. Decreased expression of EPCR in placenta may be associated with the pathogenesis of early onset severe preeclampsia. PMID- 27671050 TI - [Analysis of clinical and pathological characteristics of high- risk HPV-negative carcinoma of the uterine cervix]. AB - Objective: To study the clinical and pathological characteristics of HPV-negative cervical cancer patients. Methods: Retrospective analysis of 785 cervical cancer patients in Guangdong Women and Children Hospital from Jan. 2005 to Oct. 2015. By detecting high- risk HPV infection by flow-through hybridization genechip technique. Results: (1)Among 785 cases of cervical cancer, 71 cases were negative for HPV infection tested by genechip technique, accounting for 9.0%(71/785), and the relative light units/cut off(RLU/CO)ratios of these 71 cases were less than 1 by hybird capture II(HC-II)methods. The results showed that the positive coincident rate of genechip technique detecting result with HC-II method was 100.0%(71/71).(2)There was no difference between 43(60.6%)cases from 41-55 years old of 71 cases of HPV-negative patients and 392(54.9%)cases from 41- 55 years old of 714 cases of HPV infection patients(chi2=15.63, P=0.571). Among 71 cases of HPV-negative patients, 32 cases of patients with doing TCT, 6(18.8%)cases for normal, 10(31.2%)cases for atypical squamous cells of undetermined significance(ASCUS), 3(9.4%)cases for atypical squamous cells cannot exclude high grade squamous intraepithelial lesion(ASC-H), 3(9.4%)cases for low-grade squamous intraepithelial lesions(LSIL), 8(25.0%)cases for hight-grade squamous intraepithelial lesions(HSIL), 2(6.2%)cases for squamous cell carcinoma(SCC). And there were 391 cases of patients with doing thin-prep cytologic test(TCT)of 714 HPV infection patients, 60(15.3%)cases for normal, 61(15.6%)cases for ASCUS, 28(7.2%)cases for ASC-H, 29(7.4%)cases for LSIL, 164(41.9%)cases for HSIL, 49(12.5%)cases for SCC. There was no difference of TCT between HPV infection and HPV-negative patients(P>0.05). Among 70 cases from 71 patients with negative for HPV infection, there were 8(11.4%)cases in stage I a, 26(37.1%)cases in stage I b1, 12(17.1%)cases in stage Ib2, 11(15.7%)cases in stage IIa, 10(14.3%)cases in stage IIb, 3(4.3%)cases in stage III-IV. There were 118(16.6%)cases in stage Ia, 261(36.8%)cases in stage Ib1, 72(10.1%)cases in stage Ib2, 152(21.4%)cases in stage IIa, 87(12.3%)cases in stage IIb, 20(2.8%)cases in stage III-IV in 710 cases of HPV infection patients, in which there were no difference of clinical stage between HPV infection and HPV-negative patients(P>0.05). Among 69 cases from 71 patients HPV-negative infection, there were 51(73.9%)cases for squamous carcinoma, 13(18.8%)cases for adenocarcinoma, 5(7.2%)cases for adenosquamous carcinoma; and 593(87.2%)cases for squamous carcinoma, 38(5.6%)cases for adenocarcinoma, 39(5.7%)cases for adenosquamous carcinoma, 10(1.5%)case for others were in 680 patients of HPV infection, in which there was significant difference of adenocarcinoma between HPV infection and HPV-negative patients(chi2=11.96, P=0.001). Conclusions: Flow-through hybridization genechip technique is the method of high sensitivity to detect high-risk type HPV, as like HC-II method. HPV-negative of cervical cancer occurs mainly in 41- 55 years old. Adenocarcinoma incidence is significantly higher in HPV-negative cases than those patients with infection of HPV positive. PMID- 27671051 TI - [Study of effects of micheliolide on ovarian cancer cell lines and its mechanism]. AB - Objective: To study the roles of micheliolide on ovarian cancer cells. Methods: Firstly, human ovarian cancer cell lines HeyA8, SKOV3 and A2780/DDP were treated with different concentration of micheliolide(0.25, 0.5, 1, 2.5, 5, 10, 20, 50 MUmol/L)for 72 hours, then methyl thiazolyl tetrazolium(MTT)assay was used wo detect the growth of the human ovarian cancer cell lines and the stongest inhibited cell line were selected for the following test. Secondly, after HeyA8 cell line was treated with different concentration(5, 10, 20 MUmol/L)of micheliolide for 24 hours, the HeyA8 cell apoptosis was measured byflow cytometry. Thirdly, the expression of RelA mRNA in HeyA8 cell was detected through real-time PCR, the expressions of nuclear factor kappaB(NF-kappaB)signal pathway related protein RelA and the activited cysteinyl aspartate specific proteinase(caspase-9)were detected by western blot analysis. Results: (1)The growth of HeyA8, SKOV3 and A2780/DDP cells were all significantly inhibited after being treated with different concentration of micheliolide for 72 hours and the roles of inhibition were all concentration dependant(P<0.05). The half maximal inhibitory concentration(IC50)of HeyA8, SKOV3 and A2780/DDP were(9.8+/ 2.2),(12.0+/-2.1)and(12.8+/-1.8)MUmol/L, respectively. We chose HeyA8 cell to do the following expreriments because of its best inhibited effect.(2)After HeyA8 cell was treated with micheliolide of different concentrations, as the concentration increased(20 and 0 MUmol/L, for example), the apoptosis rate of HeyA8 cell raised from(7.2+/-1.0)% to(17.4+/-1.1)%, the percentage of survived cells reduce from(92.8 +/- 1.3)% to(82.6 +/- 1.4)%, and the relative mRNA level of RelA decreased from 1.00 +/- 0.13 to 0.18 +/- 0.00(P<0.01); furthermore, the expression of RelA protein was weaken and the activited caspase-9 protein expression was increased gradually. Conclusions: Micheliolide plays a significantly inhibited role in HeyA8, SKOV3 and A2780/DDP cells. The inhibited role of micheliolide inovarian cancer cells might through inhibiting nuclear factor-kappa B(NF-kB)signaling pathway, and inducing the expression of activited caspase-9 protein to promoting apoptosis of HeyA8 cell. PMID- 27671053 TI - Liver transplantation in transthyretin amyloidosis: Characteristics and management related to kidney disease. AB - Orthotopic liver transplantation (LT) was implemented as the inaugural disease modifying therapy for hereditary transthyretin (ATTR) amyloidosis, a systemic amyloidosis mainly affecting the peripheral nervous system and heart. The first approach to pharmacologic therapy was focused on the stabilization of the TTR tetramer; following that new advent LT was assumed as the second step of treatment, for those patients whose neuropathy becomes worse after a course of pharmacologic therapy. The renal disease has been ignored in hereditary ATTR amyloidosis. The low level of proteinuria or slight renal impairment does not suppose such a heavy glomerular and vascular amyloid deposition. Moreover, severity of renal deposits does not consistently parallel that of myelinated nerve fiber loss. These are pitfalls that limit the success of LT and suggest troublesome criteria for pharmacological therapy or LT. An algorithm of evaluation concerning renal disease and treatment options is presented and some bridges-to-decision are exposed. In stage 4 or 5 kidney disease, the approach remains to deliver combined or sequential liver-kidney transplantation in eligible patients. However, in the majority, hemodialysis is the only option even in the presence of a well-functioning liver graft. In this review, we highlight useful information to aid the transplant hepatologist in the clinical practice. PMID- 27671054 TI - All-atom molecular dynamics simulations of lung surfactant protein B: Structural features of SP-B promote lipid reorganization. AB - Lung surfactant protein B (SP-B), a 79 residue, hydrophobic protein from the saposin superfamily, plays an essential role in breathing. Because of the extreme hydrophobicity of SP-B, the experimental structure of this protein has not yet been determined. Here, we run all-atom molecular dynamics simulations using the OPLS-AA force field in GROMACS to study SP-B's structure and mechanisms for promoting lipid reorganization. Firstly, we find that the final structures indicate the need for some fine-tuning of the homology-based secondary structure predictions. Secondly, we find energetically feasible structures 1) with SP-B's helices in the plane of the bilayer, 2) with SP-B's helices inclined with respect to the bilayer, and 3) with SP-B in a closed structure interacting peripherally with the bilayer. Interestingly, SP-B structures that were bent at the hinge region between the pairs of helices promoted and/or stabilized defects in the lipid bilayer. Finally, particular salt bridge patterns and structural plasticity in the central loop and adjacent region of SP-B appeared to be involved in SP-B's lipid reorganization abilities. PMID- 27671055 TI - Paludifilum halophilum gen. nov., sp. nov., a thermoactinomycete isolated from superficial sediment of a solar saltern. AB - A novel filamentous, halophilic, thermotolerant bacterium, strain SMBg3T was isolated from superficial sediment of a solar saltern in Sfax, Tunisia. The isolate is Gram-staining-positive, aerobic, catalase- and oxidase-positive. Optimum growth occurred at 40-45 degrees C, with 10 % (w/v) NaCl and at pH 8.0 9.0. Long and well developed aerial and substrate mycelia, with long chains of fluorescent and circular spores, were observed on all tested media. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SMBg3T belongs to an independent phylogenetic lineage of the family Thermoactinomycetaceae and shows a gene sequence similarity of 94 % with Desmospora activa DSM 45169T 94.2 % with Kroppenstedtia eburnea DSM 45196T, 94.3 % with Kroppenstedtia guangzhouensis KCTC 29149T, 94.3 % with Melghirimyces algeriensisDSM 45474T and 94.5 % with Salinithrix halophila CECT 8506T. The predominant menaquinone is MK-7, but MK-8 and some minor unidentified components are also present in trace amounts. The major cellular fatty acids are anteiso-C15 : 0, iso-C15 : 0 and iso-C17 : 0. In addition to four major polar lipids identified as phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylmethylethanolamine, five minor unknown lipids were detected in cell membranes. The DNA G+C content of strain SMBg3T is 51.2 mol%. Strain SMBg3T is distinct from recognized genera of the family Thermoactinomycetaceae by morphological, biochemical and chemotaxonomic characteristics. On the basis of physiological and phylogenetic data, strain SMBg3T represents a novel species of a new genus in the family Thermoactinomycetaceae for which the name Paludifilum halophilum gen. nov., sp. nov. is proposed. The type strain of the type species is SMBg3T (=DSM 102817T=CCUG 68698T). PMID- 27671052 TI - Widespread natural variation of DNA methylation within angiosperms. AB - BACKGROUND: DNA methylation is an important feature of plant epigenomes, involved in the formation of heterochromatin and affecting gene expression. Extensive variation of DNA methylation patterns within a species has been uncovered from studies of natural variation. However, the extent to which DNA methylation varies between flowering plant species is still unclear. To understand the variation in genomic patterning of DNA methylation across flowering plant species, we compared single base resolution DNA methylomes of 34 diverse angiosperm species. RESULTS: By analyzing whole-genome bisulfite sequencing data in a phylogenetic context, it becomes clear that there is extensive variation throughout angiosperms in gene body DNA methylation, euchromatic silencing of transposons and repeats, as well as silencing of heterochromatic transposons. The Brassicaceae have reduced CHG methylation levels and also reduced or loss of CG gene body methylation. The Poaceae are characterized by a lack or reduction of heterochromatic CHH methylation and enrichment of CHH methylation in genic regions. Furthermore, low levels of CHH methylation are observed in a number of species, especially in clonally propagated species. CONCLUSIONS: These results reveal the extent of variation in DNA methylation in angiosperms and show that DNA methylation patterns are broadly a reflection of the evolutionary and life histories of plant species. PMID- 27671056 TI - Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii. AB - Sulbactam is being considered as an alternative concomitant medication with other effective antibiotics for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections. Pathophysiological changes in critically ill patients with severe sepsis, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors in determining therapeutic success. The aims of this study were (i) to examine the population PK parameters and (ii) to assess the probability of target attainment (PTA) for sulbactam in patients with severe sepsis caused by A. baumannii PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 4th day of drug administration in 27 patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the plasma drug concentration remained above the MIC (T>MIC) and 60% T>MIC The central and peripheral volumes of distribution were 14.56 and 9.55 liters, respectively, and total clearances of sulbactam were 2.26 liters/h and 7.64 liters/h in patients aged >65 years and <=65 years, respectively. The high PTAs (>=90%) for targets of 40% T>MIC and 60% T>MIC with a MIC of 4 MUg/ml were observed when sulbactam was administered by a 4-h infusion of 1 g every 12 h and 1 g every 8 h, respectively. Sulbactam would be an alternative antibiotic option to coadminister with colistin for the treatment of infections caused by MDR A. baumannii However, for pathogens with MICs of >4 MUg/ml, higher dosage regimens of sulbactam are required. PMID- 27671057 TI - In Vitro Activities of Omadacycline (PTK 0796) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas. AB - In vitro activities of omadacycline, a new aminomethylcycline, were determined for Mycoplasma and Ureaplasma spp. and compared with those of azithromycin, clindamycin, moxifloxacin, tetracycline, and doxycycline. All omadacycline MICs were <2 MUg/ml. MIC90s were 0.063 MUg/ml for Mycoplasma hominis, 0.25 MUg/ml for Mycoplasma pneumoniae, and 2 MUg/ml for Ureaplasma spp. Omadacycline had the lowest MIC90 among all drugs tested against M. hominis Omadacycline activity was not affected by macrolide, tetracycline, or fluoroquinolone resistance. PMID- 27671058 TI - Transposition of Tn125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii. AB - The blaNDM-1 gene encodes a carbapenemase that confers resistance to almost all beta-lactams, including last-resort carbapenems. This is increasingly reported worldwide in nosocomial and community-acquired Gram-negative bacteria. Acinetobacter baumannii is an important opportunistic pathogen that is considered an intermediate reservoir for the blaNDM-1 gene. In this species, the blaNDM-1 gene is located within the Tn125 composite transposon. The mechanism driving the mobility of Tn125 has not yet been elucidated. Here we experimentally demonstrated the transposition of Tn125 in A. baumannii Systematic 3-bp duplication of the target site, being the signature of transposition, was evidenced. The target site consensus sequence for Tn125 transposition was found to be GC enriched at the duplicated 3 bp and AT rich in the vicinity. Transposition frequency was not influenced by temperature changes or by exposure to subinhibitory concentrations of various antibiotics. This work is the first direct evidence of the functionality of a composite transposon in A. baumannii It provides a mechanistic clue for the dissemination of the blaNDM-1 gene in Acinetobacter spp. and subsequently among Enterobacteriaceae. PMID- 27671059 TI - Esculentin-1a-Derived Peptides Promote Clearance of Pseudomonas aeruginosa Internalized in Bronchial Cells of Cystic Fibrosis Patients and Lung Cell Migration: Biochemical Properties and a Plausible Mode of Action. AB - Pseudomonas aeruginosa is the major microorganism colonizing the respiratory epithelium in cystic fibrosis (CF) sufferers. The widespread use of available antibiotics has drastically reduced their efficacy, and antimicrobial peptides (AMPs) are a promising alternative. Among them, the frog skin-derived AMPs, i.e., Esc(1-21) and its diastereomer, Esc(1-21)-1c, have recently shown potent activity against free-living and sessile forms of P. aeruginosa Importantly, this pathogen also escapes antibiotics treatment by invading airway epithelial cells. Here, we demonstrate that both AMPs kill Pseudomonas once internalized into bronchial cells which express either the functional or the DeltaF508 mutant of the CF transmembrane conductance regulator. A higher efficacy is displayed by Esc(1-21) 1c (90% killing at 15 MUM in 1 h). We also show the peptides' ability to stimulate migration of these cells and restore the induction of cell migration that is inhibited by Pseudomonas lipopolysaccharide when used at concentrations mimicking lung infection. This property of AMPs was not investigated before. Our findings suggest new therapeutics that not only eliminate bacteria but also can promote reepithelialization of the injured infected tissue. Confocal microscopy indicated that both peptides are intracellularly localized with a different distribution. Biochemical analyses highlighted that Esc(1-21)-1c is significantly more resistant than the all-l peptide to bacterial and human elastase, which is abundant in CF lungs. Besides proposing a plausible mechanism underlying the properties of the two AMPs, we discuss the data with regard to differences between them and suggest Esc(1-21)-1c as a candidate for the development of a new multifunctional drug against Pseudomonas respiratory infections. PMID- 27671060 TI - Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum beta Lactamase and Its Complexes with Moxalactam and Imipenem. AB - BEL-1 is an acquired class A extended-spectrum beta-lactamase (ESBL) found in Pseudomonas aeruginosa clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obtained at pH 5.6, and the structure of native BEL-1 was determined from orthorhombic and monoclinic crystal forms at 1.60-A and 1.48-A resolution, respectively. By soaking native BEL-1 crystals, complexes with imipenem (monoclinic form, 1.79-A resolution) and moxalactam (orthorhombic form, 1.85-A resolution) were also obtained. In the acyl-enzyme complexes, imipenem and moxalactam differ by the position of the alpha-substituent and of the carbonyl oxygen (in or out of the oxyanion hole). More surprisingly, the Omega-loop, which includes the catalytically relevant residue Glu166, was found in different conformations in the various subunits, resulting in the Glu166 side chain being rotated out of the active site or even in displacement of its Calpha atom up to approximately 10 A. A BEL-1 variant showing the single Leu162Phe substitution (BEL-2) confers a higher level of resistance to CAZ, CTX, and FEP and shows significantly lower Km values than BEL-1, especially with oxyiminocephalosporins. BEL-1 Leu162 is located at the beginning of the Omega-loop and is surrounded by Phe72, Leu139, and Leu148 (contact distances, 3.5 to 3.9 A). This small hydrophobic cavity could not reasonably accommodate the bulkier Phe162 found in BEL-2 without altering neighboring residues or the Omega-loop itself, thus likely causing an important alteration of the enzyme kinetic properties. PMID- 27671061 TI - A Bioluminescent Francisella tularensis SCHU S4 Strain Enables Noninvasive Tracking of Bacterial Dissemination and the Evaluation of Antibiotics in an Inhalational Mouse Model of Tularemia. AB - Bioluminescence imaging (BLI) enables real-time, noninvasive tracking of infection in vivo and longitudinal infection studies. In this study, a bioluminescent Francisella tularensis strain, SCHU S4-lux, was used to develop an inhalational infection model in BALB/c mice. Mice were infected intranasally, and the progression of infection was monitored in real time using BLI. A bioluminescent signal was detectable from 3 days postinfection (3 dpi), initially in the spleen and then in the liver and lymph nodes, before finally becoming systemic. The level of bioluminescent signal correlated with bacterial numbers in vivo, enabling noninvasive quantification of bacterial burdens in tissues. Treatment with levofloxacin (commencing at 4 dpi) significantly reduced the BLI signal. Furthermore, BLI was able to distinguish noninvasively between different levofloxacin treatment regimens and to identify sites of relapse following treatment cessation. These data demonstrate that BLI and SCHU S4-lux are suitable for the study of F. tularensis pathogenesis and the evaluation of therapeutics for tularemia. PMID- 27671063 TI - Pharmacodynamics of Ceftolozane Combined with Tazobactam against Enterobacteriaceae in a Neutropenic Mouse Thigh Model. AB - Ceftolozane is a new broad-spectrum cephalosporin and is combined with tazobactam to broaden the activity of ceftolozane against strains producing extended spectrum beta-lactamases (ESBLs). We determined the pharmacodynamics (PD) of the combination in the neutropenic mouse thigh model to determine the optimal exposure of tazobactam. Treatment of CD-1 neutropenic mice was started 2 h after infection with ceftolozane every 2 h (q2h) alone or in combination with tazobactam at different dosing frequencies for 24 h, and the number of CFU in the thighs was determined before and after treatment. The maximum effect model was fit to the dose-response and the pharmacokinetic/PD index (PDI)-response to determine the PDI values for ceftolozane alone and ceftolozane in combination with tazobactam resulting in a static effect and a 1-log kill. The effect of tazobactam was dependent on the percentage of time that the free drug concentration remained above the concentration threshold (percent [Formula: see text]), whereby dosing q2h was more efficacious than dosing every 8 h (q8h), reducing the tazobactam daily dose by a factor 6.9 to 59.0 (n = 3 strains) to obtain a static effect. Using R2 as an indicator of the best fit of the percent [Formula: see text]-response relationships, the concentration threshold best correlating with the response varied from 0.5 to 2 mg/liter, depending on the strain. A similar result was obtained when the q2h and q8h regimens were analyzed. For all isolates tested, the mean [Formula: see text] for 0.5 mg/liter tazobactam was 28.2% (range, 17.5 to 45.8%) and 44.4% (range, 26.6 to 54.7%) for a static effect and a 1-log kill, respectively, at ceftolozane exposures that produced a ceftolozane concentration of 4 mg/liter (a concentration greater than the MIC) for 33.9 to 63.3% of a 24-h period under steady-state pharmacokinetic conditions. The main PDI that correlated with the effect of tazobactam was the [Formula: see text] achieved with a CT of 0.5 mg/liter tazobactam. PMID- 27671062 TI - Association between embB Codon 306 Mutations, Phenotypic Resistance Profiles, and Genotypic Characterization in Clinical Mycobacterium tuberculosis Isolates from Hebei, China. AB - Ethambutol (EMB) is an essential first-line drug for tuberculosis (TB) treatment. Nucleotide substitutions at embB codon 306 (embB306) have been proposed to be a potential marker for EMB resistance and a predictor of broad drug resistance in clinical Mycobacterium tuberculosis isolates. However, discordant findings about the association between embB306 mutations and EMB resistance were reported. Hebei Province is located in the Beijing-Tianjin-Hebei integration region in China; however, little information about the genetic diversity of the embB locus in this area is available. In this study, we sequenced the region surrounding embB306 (codons 207 to 445) in 62 ethambutol-resistant (EMBr) isolates, 214 ethambutol susceptible isolates resistant to other first-line drugs (EMBs isolates), and 100 pan-sensitive isolates. Our data indicated that none of the pan-sensitive isolates showed mutations at embB306 and 63 drug-resistant isolates harbored embB306 substitutions, with these substitutions being found in 56.5% (35/62) of EMBr isolates and 13.1% (28/214) of EMBs isolates. A significant association between the embB306 mutation and resistance to isoniazid, rifampin, EMB, and multiple drugs was observed, and the rate of mutation of embB306 increased with increasing numbers of first-line drugs to which the isolates were resistant. The embB306 mutation is not the sole causative factor for EMB resistance, and the poor sensitivity limits its utility as a marker for drug-resistant TB. However, it may be a potential marker for broad drug resistance, especially for multidrug resistance. The mycobacterial interspersed repetitive unit-variable-number tandem repeat profiles may serve as markers for predicting the embB306 substitutions that may occur in drug-resistant M. tuberculosis isolates under antimicrobial selection pressure. PMID- 27671064 TI - Mycobacterium tuberculosis Arylamine N-Acetyltransferase Acetylates and Thus Inactivates para-Aminosalicylic Acid. AB - Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) is able to acetylate para-aminosalicylic acid (PAS) both in vitro and in vivo as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in M. tuberculosis results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from M. tuberculosis is able to inactivate PAS by acetylating the compound. PMID- 27671065 TI - Antimold Prophylaxis May Reduce the Risk of Invasive Fusariosis in Hematologic Patients with Superficial Skin Lesions with Positive Culture for Fusarium. AB - Hematologic patients with superficial skin lesions on admission growing Fusarium spp. are at a high risk for developing invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing invasive fusariosis in these patients. Between August 2008 and December 2014, patients with acute leukemia or aplastic anemia and recipients of hematopoietic cell transplants were screened on admission with dermatologic and direct exams and fungal cultures of superficial skin lesions. Until November 2009, no interventions were made. Beginning in December 2009, patients with baseline skin lesions and a direct exam and/or culture suggestive of the presence of Fusarium spp. received prophylaxis with voriconazole or posaconazole. Skin lesions in the extremities (mostly onychomycosis and interdigital intertrigo) were present on admission in 88 of 239 episodes (36.8%); 44 lesions had hyaline septate hyphae identified by direct exam, and cultures from 11 lesions grew Fusarium spp. Antimold prophylaxis was given for 20 episodes (voriconazole for 17 and posaconazole for 3). Invasive fusariosis was diagnosed in 14 episodes (5.8%). Among patients with baseline skin lesions with positive cultures for Fusarium spp., 4 of 5 without antimold prophylaxis developed invasive fusariosis versus 0 of 6 with antimold prophylaxis (P = 0.01; 95% confidence interval for the difference between proportions, 22% to 96%). Primary antifungal prophylaxis with an antimold azole may prevent the occurrence of invasive fusariosis in high-risk hematologic patients with superficial skin lesions on admission growing Fusarium spp. PMID- 27671067 TI - Presence of the optrA Gene in Methicillin-Resistant Staphylococcus sciuri of Porcine Origin. AB - A total of 57 methicillin-resistant Staphylococcus aureus (MRSA) isolates and 475 methicillin-resistant coagulase-negative staphylococci (MRCoNS) collected from pigs in the Guangdong province of China in 2014 were investigated for the presence of the novel oxazolidinone-phenicol resistance gene optrA The optrA gene was detected in 6.9% (n = 33) of the MRCoNS, all of which were Staphylococcus sciuri isolates, but in none of the MRSA isolates. Five optrA-carrying methicillin-resistant (MR) S. sciuri isolates also harbored the multiresistance gene cfr Pulsed-field gel electrophoresis (PFGE) and dru typing of the 33 optrA carrying MR S. sciuri isolates revealed 25 patterns and 5 sequence types, respectively. S1 nuclease PFGE and Southern blotting confirmed that optrA was located in the chromosomal DNAs of 29 isolates, including 1 cfr-positive isolate. The remaining four isolates harbored a ~35-kb pWo28-3-like plasmid on which optrA and cfr were located together with other resistance genes, as confirmed by sequence analysis. Six different types of genetic environments (types I to VI) of the chromosome-borne optrA genes were identified; these types had the optrA gene and its transcriptional regulator araC in common. Tn558 was found to be associated with araC-optrA in types II to VI. The optrA gene in types II and III was found in close proximity to the ccr gene complex of the respective staphylococcal cassette chromosome mec element (SCCmec). Since oxazolidinones are last-resort antimicrobial agents for the control of serious infections caused by methicillin-resistant staphylococci in humans, the location of the optrA gene close to the ccr complex is an alarming observation. PMID- 27671066 TI - Whole-Genome Sequencing Identifies In Vivo Acquisition of a blaCTX-M-27-Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection. AB - We report a case of ceftriaxone treatment failure for bacteremia caused by Salmonella enterica subsp. enterica serovar Typhimurium, due to the in vivo acquisition of a blaCTX-M-27-encoding IncFII group transmissible plasmid. The original beta-lactamase-susceptible isolate ST882S was replaced by the resistant isolate ST931R during ceftriaxone treatment. After relapse, treatment was changed to ciprofloxacin, and the patient recovered. Isolate ST931R could transfer resistance to Escherichia coli at 37 degrees C. We used whole-genome sequencing of ST882S and ST931R, the E. coli transconjugant, and isolated plasmid DNA to unequivocally show that ST882S and ST931R had identical chromosomes, both having 206 identical single-nucleotide polymorphisms (SNPs) versus S Typhimurium 14028s. We assembled a complete circular genome for ST931R, to which ST882S reads mapped with no SNPs. ST882S and ST931R were isogenic except for the presence of three additional plasmids in ST931R. ST931R and the E. coli transconjugant were ceftriaxone resistant due to the presence of a 60.5-kb IS26-flanked, blaCTX-M-27 encoding IncFII plasmid. Compared to 14082s, ST931R has almost identical Gifsy-1, Gifsy-2, and ST64B prophages, lacks Gifsy-3, and instead carries a unique Fels-2 prophage related to that found in LT2. ST882S and ST931R both had a 94-kb virulence plasmid showing >99% identity with pSLT14028s and a cryptic 3,904-bp replicon; ST931R also has cryptic 93-kb IncI1 and 62-kb IncI2 group plasmids. To the best of our knowledge, in vivo acquisition of extended-spectrum beta lactamase resistance by S Typhimurium and blaCTX-M-27 genes in U.S. isolates of Salmonella have not previously been reported. PMID- 27671068 TI - Clonal Dissemination of Pseudomonas aeruginosa Sequence Type 235 Isolates Carrying blaIMP-6 and Emergence of blaGES-24 and blaIMP-10 on Novel Genomic Islands PAGI-15 and -16 in South Korea. AB - A total of 431 Pseudomonas aeruginosa clinical isolates were collected from 29 general hospitals in South Korea in 2015. Antimicrobial susceptibility was tested by the disk diffusion method, and MICs of carbapenems were determined by the agar dilution method. Carbapenemase genes were amplified by PCR and sequenced, and the structures of class 1 integrons surrounding the carbapenemase gene cassettes were analyzed by PCR mapping. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed for strain typing. Whole-genome sequencing was carried out to analyze P. aeruginosa genomic islands (PAGIs) carrying the blaIMP-6, blaIMP-10, and blaGES-24 genes. The rates of carbapenem-nonsusceptible and carbapenemase-producing P. aeruginosa isolates were 34.3% (148/431) and 9.5% (41/431), respectively. IMP-6 was the most prevalent carbapenemase type, followed by VIM-2, IMP-10, and GES-24. All carbapenemase genes were located on class 1 integrons of 6 different types on the chromosome. All isolates harboring carbapenemase genes exhibited genetic relatedness by PFGE (similarity > 80%); moreover, all isolates were identified as sequence type 235 (ST235), with the exception of two ST244 isolates by MLST. The blaIMP-6, blaIMP-10, and blaGES-24 genes were found to be located on two novel PAGIs, designated PAGI-15 and PAGI 16. Our data support the clonal spread of an IMP-6-producing P. aeruginosa ST235 strain, and the emergence of IMP-10 and GES-24 demonstrates the diversification of carbapenemases in P. aeruginosa in Korea. PMID- 27671069 TI - Kluyvera ascorbata Strain from Hospital Sewage Carrying the mcr-1 Colistin Resistance Gene. AB - The newly identified plasmid-borne colistin resistance gene mcr-1 was found in a Kluyvera ascorbata isolate from hospital sewage in China. mcr-1 was carried by a 57-kb self-transmissible IncI2 plasmid. Unlike in a previous report, mcr-1 was not associated with ISApl1 and was inserted into a gene encoding a putative membrane protein by an unknown mechanism. This study highlights that mcr-1 has spread to multiple bacterial species. PMID- 27671070 TI - Antibiofilm Activity and Synergistic Inhibition of Staphylococcus aureus Biofilms by Bactericidal Protein P128 in Combination with Antibiotics. AB - P128 is an antistaphylococcal protein, comprising a cell wall-degrading enzymatic region and a Staphylococcus-specific binding region, which possesses specific and potent bactericidal activity against sensitive and drug-resistant strains of Staphylococcus aureus To explore P128's ability to kill S. aureus in a range of environments relevant to clinical infection, we investigated the anti-S. aureus activity of P128 alone and in combination with standard-of-care antibiotics on planktonic and biofilm-embedded cells. P128 was found to have potent antibiofilm activity on preformed S. aureus biofilms as detected by CFU reduction and a colorimetric minimum biofilm inhibitory concentration (MBIC) assay. Scanning electron microscopic images of biofilms formed on the surfaces of microtiter plates and on catheters showed that P128 at low concentrations could destroy the biofilm structure and lyse the cells. When it was tested in combination with antibiotics which are known to be poor inhibitors of S. aureus in biofilms, such as vancomycin, gentamicin, ciprofloxacin, linezolid, and daptomycin, P128 showed highly synergistic antibiofilm activity that resulted in much reduced MBIC values for P128 and the individual antibiotics. The synergistic effect was seen for both sensitive and resistant isolates of S. aureus Additionally, in an in vitro mixed biofilm model mimicking the wound infection environment, P128 was able to prevent biofilm formation by virtue of its anti-Staphylococcus activity. The potent S. aureus biofilm-inhibiting activity of P128 both alone and in combination with antibiotics is an encouraging sign for the development of P128 for treatment of complicated S. aureus infections involving biofilms. PMID- 27671071 TI - Decreased Susceptibility to Tigecycline Mediated by a Mutation in mlaA in Escherichia coli Strains. PMID- 27671072 TI - A Novel Genome-Editing Platform for Drug-Resistant Acinetobacter baumannii Reveals an AdeR-Unrelated Tigecycline Resistance Mechanism. AB - Infections with the Gram-negative coccobacillus Acinetobacter baumannii are a major threat in hospital settings. The progressing emergence of multidrug resistant clinical strains significantly reduces the treatment options for clinicians to fight A. baumannii infections. The current lack of robust methods to genetically manipulate drug-resistant A. baumannii isolates impedes research on resistance and virulence mechanisms in clinically relevant strains. In this study, we developed a highly efficient and versatile genome-editing platform enabling the markerless modification of the genome of A. baumannii clinical and laboratory strains, regardless of their resistance profiles. We applied this method for the deletion of AdeR, a transcription factor that regulates the expression of the AdeABC efflux pump in tigecycline-resistant A. baumannii, to evaluate its function as a putative drug target. Loss of adeR reduced the MIC90 of tigecycline from 25 MUg/ml in the parental strains to 3.1 MUg/ml in the DeltaadeR mutants, indicating its importance in the drug resistance phenotype. However, 60% of the clinical isolates remained nonsusceptible to tigecycline after adeR deletion. Evolution of artificial tigecycline resistance in two strains followed by whole-genome sequencing revealed loss-of-function mutations in trm, suggesting its role in an alternative AdeABC-independent tigecycline resistance mechanism. This finding was strengthened by the confirmation of trm disruption in the majority of the tigecycline-resistant clinical isolates. This study highlights the development and application of a powerful genome-editing platform for A. baumannii enabling future research on drug resistance and virulence pathways in clinically relevant strains. PMID- 27671073 TI - rRNA Operon Copy Number Can Explain the Distinct Epidemiology of Hospital Associated Methicillin-Resistant Staphylococcus aureus. AB - The distinct epidemiology of original hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and early community-associated MRSA (CA-MRSA) is largely unexplained. S. aureus carries either five or six rRNA operon copies. Evidence is provided for a scenario in which MRSA has adapted to the hospital environment by rRNA operon loss (six to five copies) due to antibiotic pressure. Early CA-MRSA, in contrast, results from wild-type methicillin-susceptible S. aureus (MSSA) that acquired mecA without loss of an rRNA operon. Of the HA-MRSA isolates (n = 77), 67.5% had five rRNA operon copies, compared to 23.2% of the CA MRSA isolates (n = 69) and 7.7% of MSSA isolates (n = 195) (P < 0.001). In addition, 105 MSSA isolates from cystic fibrosis patients were tested, because these patients are repeatedly treated with antibiotics; 32.4% of these isolates had five rRNA operon copies. For all subsets, a correlation between resistance profile and rRNA copy number was found. Furthermore, we showed that in vitro antibiotic pressure may result in rRNA operon copy loss. We also showed that without antibiotic pressure, S. aureus isolates containing six rRNA copies are more fit than isolates with five copies. We conclude that HA-MRSA and cystic fibrosis isolates most likely have adapted to an environment with high antibiotic pressure by the loss of an rRNA operon copy. This loss has facilitated resistance development, which promoted survival in these niches. However, strain fitness decreased, which explains their lack of success in the community. In contrast, CA MRSA isolates retained six rRNA operon copies, rendering them fitter and thereby able to survive and spread in the community. PMID- 27671077 TI - Emeritus Professor William (Bill) Towler Clark BVMS, PhD, FRCVS 1935 - 2015. PMID- 27671074 TI - Topical Decolonization Does Not Eradicate the Skin Microbiota of Community Dwelling or Hospitalized Adults. AB - Topical antimicrobials are often employed for decolonization and infection prevention and may alter the endogenous microbiota of the skin. The objective of this study was to compare the microbial communities and levels of richness and diversity in community-dwelling subjects and intensive care unit (ICU) patients before and after the use of topical decolonization protocols. We enrolled 15 adults at risk for Staphylococcus aureus infection. Community subjects (n = 8) underwent a 5-day decolonization protocol (twice daily intranasal mupirocin and daily dilute bleach-water baths), and ICU patients (n = 7) received daily chlorhexidine baths. Swab samples were collected from 5 anatomic sites immediately before and again after decolonization. A variety of culture media and incubation environments were used to recover bacteria and fungi; isolates were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Overall, 174 unique organisms were recovered. Unique communities of organisms were recovered from the community-dwelling and hospitalized cohorts. In the community-dwelling cohort, microbial richness and diversity did not differ significantly between collections across time points, although the number of body sites colonized with S. aureus decreased significantly over time (P = 0.004). Within the hospitalized cohort, richness and diversity decreased over time compared to those for the enrollment sampling (from enrollment to final sampling, P = 0.01 for both richness and diversity). Topical antimicrobials reduced the burden of S. aureus while preserving other components of the skin and nasal microbiota. PMID- 27671078 TI - Survey of horse transportation in Australia: issues and practices. AB - OBJECTIVE: To survey amateur and professional participants on equine transportation management, practices and outcomes in Australia. METHODS: An online survey targeting people who organised horse movements at least monthly was made available to a broad cross-section of amateur and professional equine associations. Respondents were invited to provide demographic details and information relating to their routine transportation management practices and their experiences of issues relating to the transportation of horses. RESULTS: Of 797 usable responses involving approximately 17,000 horses and 313,000 individual horse transport events, transport-related behavioural problems were reported by 38% of respondents, particularly at loading. Transport-related health problems had been experienced during or after transportation by horses in the care of 67% of respondents. The most common problems reported were traumatic injuries (45.0%), diarrhoea (20.0%), muscular problems (13.0%), respiratory problems (12.3%), overheating (10.5%) and colic (10.3%). In the 2 years reviewed in the survey, 9.4% of participants reported at least one case of transport-associated pneumonia and 35 horses had died, most commonly from fractures, colic or pneumonia. Although respondents identifying as amateurs transported horses less frequently and over shorter distances, the incidence of transport-related problems was similar between amateurs and professionals. Respondents reported specific precautions before, during and after transportation, although management was often not compliant with the Australian Code of horse transportation. CONCLUSIONS: Responses indicated that there remains a substantial risk of adverse welfare and health outcomes for horses transported in Australia and management practices reported may not be compliant with current recommendations for transportation. PMID- 27671075 TI - Changes in cortico-spinal excitability following uphill versus downhill treadmill exercise. AB - An acute bout of aerobic exercise induces neuroplasticity in the motor cortex. Moreover, paired associative stimulation (PAS) is known to induce neuroplasticity in M1. However, the possible influence of the type of exercise on the neuroplastic changes remains unknown. The present study investigated the effects of two different modes of muscle contraction produced during locomotor exercise on changes in corticospinal (CS) excitability. Subjects performed two 30-min treadmill exercises at an intensity corresponding to 60% of their maximal heart rate with either a +10% (uphill) or -10% (downhill) slope. These exercises were followed or not by paired associative stimulation method (PAS25) which consisted of 200 paired stimuli (0.25Hz, 15min) of median nerve electrical stimulation followed by transcranial magnetic stimulation of the hand M1 area (ISI 25ms). Motor evoked potentials (MEP), assessed through abductor pollicis brevis (APB) activity were obtained before exercise, at 5min, 15min and 30min after exercise. A significant (P<0.05) increase of the MEP amplitude was observed 30min after both exercises but was not different between the two modes of locomotion. On the contrary, MEP amplitude with PAS25 increased only 30min after downhill exercise. We conclude that sub-maximal treadmill exercise increases CS excitability within a period of 30min. However, the predominant mode of muscle contraction during uphill versus downhill locomotion does not influence CS excitability when assessed using a non-exercised muscle. However, results from PAS25 suggest that specific neuroplastic changes occur likely due to homeostatic mechanisms induced by exercise plus a PAS protocol. PMID- 27671079 TI - Osteopetrosis in a neonatal donkey. AB - Osteopetrosis is a rare disorder characterised by a defect in osteoclastic bone resorption. This report describes osteopetrosis in a neonatal donkey that suffered a displaced tibial fracture. Radiographic examination identified generalised reduction in medullary cavity size, thickened mid-diaphyseal cortices and conical metaphyseal bone extending toward the mid-diaphysis of long bones. Postmortem examination identified additional fractures and brittle bones. Histologically, osteoclasts were absent in multiple bone sections. Diaphyseal cortices consisted of concentric bone lamellae with marrow tissue infiltration. Large wedges of secondary spongiosa extended from the metaphyseal growth plate. Clinical and histopathological features were similar to an osteoclast-deficient, autosomal recessive form of osteopetrosis in humans. PMID- 27671080 TI - Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle. AB - OBJECTIVE: This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. METHODS: Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. RESULTS: The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. CONCLUSION: The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. PMID- 27671081 TI - Phenotypic and genotypic profiling of antimicrobial resistance in enteric Escherichia coli communities isolated from finisher pigs in Australia. AB - OBJECTIVE: To assess herd-to-herd variation in antimicrobial resistance phenotypes and associated antimicrobial resistance genes (ARGs) in faecal commensal Escherichia coli communities isolated from Australian slaughter-age pigs. METHODS: Hydrophobic grid-membrane filtration (HGMF) was used to screen populations of E. coli isolated from faecal samples obtained from pigs prior to or at slaughter. Multiplex PCRs were applied to the pooled DNA extracted from the samples to identify specific ARGs. METHODS: Pooled faecal samples from 30 finishers, from 72 different Australian pig farms, produced 5003 isolates for screening. HGMF techniques and image analysis were used to confirm E. coli resistance phenotypes to four antimicrobial agents (ampicillin, gentamicin, florfenicol and ceftiofur) using selective agars. Multiplex PCRs were performed on DNA from pooled samples for 35 ARGs associated with seven chemical classes. RESULTS: The prevalence of E. coli isolates showing no resistance to any of the drugs was 50.2% (95% confidence interval (CI) 41.8-58.6%). Ceftiofur resistance was very low (1.8%; CI 0.8-3.9%) and no ARGs associated with 3rd-generation cephalosporin resistance were detected. By contrast, ampicillin (29.4%, CI 22.8 37.0%), florfenicol (24.3%, CI 17.8-32.3%) and gentamicin (CI 17.5%, 10.7-27.2%) resistance prevalence varied greatly between farms and associated ARGs were common. The most common combined resistance phenotype was ampicillin-florfenicol. CONCLUSION: The use of registered antimicrobials in Australian pigs leads to the enteric commensal populations acquiring associated ARGs. However, despite a high intensity of sampling, ARGs imparting resistance to the critically important 3rd generation cephalosporins were not detected. PMID- 27671082 TI - Stabilisation of periarticular fractures and osteotomies with a notched head locking T-plate. AB - OBJECTIVE: To report the clinical outcomes and complications of small animals that had articular or periarticular fractures or osteotomies stabilised with a notched head locking T-plate. METHODS: Medical records were searched retrospectively to identify animals that had a notched head locking T-plate used to stabilise a small articular or periarticular bone fragment. RESULTS: Nine dogs and two cats had an articular or periarticular bone fragment stabilised with a 2.0- or 2.4-mm notched head locking T-plate (12 procedures). The median body weight was 4.7 kg. The plate was modified by removing holes in 10/12 procedures and a combination of locking and non-locking screws were used in 7/12 procedures. All fractures or osteotomies progressed to clinical union. There were two intraoperative complications (intra-articular screw placement and overlong screw) and two postoperative complications (skin necrosis and stress protection) CONCLUSIONS: This study reports the successful use of a 2.0- or 2.4-mm notched head locking T-plate for articular or periarticular fractures or osteotomies in a variety of small-breed dogs and cats. Care must be taken to prevent inadvertent penetration of the articular surface, particularly in regions such as the proximal tibia. The ability to modify the plate dimensions intraoperatively proved beneficial in most cases. PMID- 27671083 TI - Prothrombin time and activated partial thromboplastin time using a point-of-care analyser (Abaxis VSpro(r)) in Bennett's wallabies (Macropus rufogriseus). AB - There are few reports of coagulation times in marsupial species. Blood samples collected from 14 Bennett's wallabies (Macropus rufogriseus) under anaesthesia during routine health assessments were analysed for prothrombin time (PT) and activated partial thromboplastin time (aPTT) using a point-of-care analyser (POC) (Abaxis VSPro(r)). The wallabies had an aPTT mean of 78.09 s and median of 78.1 s. The PT for all wallabies was greater than 35 s, exceeding the longest time measured on the POC. Although PT was significantly longer, aPTT was similar to the manufacturer's domestic canine reference range. PMID- 27671084 TI - Live and inactivated vaccine regimens against caecal Salmonella Typhimurium colonisation in laying hens. AB - OBJECTIVE: In Australia, Salmonella serovar Typhimurium (S. Typhimurium) is the predominant zoonotic serovar in humans and is frequently isolated from layer hens. Vaccination against this serovar has been previously shown to be effective in broilers and the aim of this current study was to assess and determine the best vaccination strategy (live or inactivated) to minimise caecal colonisation by S. Typhimurium. METHODS: A long-term experiment (56 weeks) was conducted on ISABROWN pullets using a commercial live aroA deleted mutant S. Typhimurium vaccine and an autogenous inactivated multivalent Salmonella vaccine (containing serovars Typhimurium, Infantis, Montevideo and Zanzibar). These vaccines were administered PO or by SC or IM injection, either alone or in combination. Pullets were vaccinated throughout rearing (to 18 weeks of age) and sequentially bled for antibody titre levels. The birds, vaccinated and controls, were challenged orally with a field isolate of S. Typhimurium at different ages, held for 21 days post challenge, then euthanased and their caeca cultured for the presence of Salmonella. RESULTS: None of the oral live-vaccinated groups exhibited lasting protection. When administered twice, the inactivated vaccine gave significant protection at 17 weeks of age and the live vaccine given by SC injection given twice produced significant protection at 17, 25 and 34 weeks. CONCLUSIONS: Vaccination regimens that included parenteral administration of live or inactivated vaccines and thus achieved positive serum antibody levels were able to provide protection against challenge. Hence, vaccination may play a useful role in a management strategy for Salmonella carriage in layer flocks. PMID- 27671086 TI - Development of steady-state electrical-heating fluorescence-sensing (SEF) technique for thermal characterization of one dimensional (1D) structures by employing graphene quantum dots (GQDs) as temperature sensors. AB - A fluorescence signal has been demonstrated as an effective implement for micro/nanoscale temperature measurement which can be realized by either direct fluorescence excitation from materials or by employing nanoparticles as sensors. In this work, a steady-state electrical-heating fluorescence-sensing (SEF) technique is developed for the thermal characterization of one-dimensional (1D) materials. In this method, the sample is suspended between two electrodes and applied with steady-state Joule heating. The temperature response of the sample is monitored by collecting a simultaneous fluorescence signal from the sample itself or nanoparticles uniformly attached on it. According to the 1D heat conduction model, a linear temperature dependence of heating powers is obtained, thus the thermal conductivity of the sample can be readily determined. In this work, a standard platinum wire is selected to measure its thermal conductivity to validate this technique. Graphene quantum dots (GQDs) are employed as the fluorescence agent for temperature sensing. Parallel measurement by using the transient electro-thermal (TET) technique demonstrates that a small dose of GQDs has negligible influence on the intrinsic thermal property of platinum wire. This SEF technique can be applied in two ways: for samples with a fluorescence excitation capability, this method can be implemented directly; for others with weak or no fluorescence excitation, a very small portion of nanoparticles with excellent fluorescence excitation can be used for temperature probing and thermophysical property measurement. PMID- 27671087 TI - Is it too difficult for disadvantaged applicants to get into medical school? PMID- 27671090 TI - A case of traumatic long thoracic nerve suffering: High-frequency ultrasound finding. PMID- 27671088 TI - Predictive computational phenotyping and biomarker discovery using reference-free genome comparisons. AB - BACKGROUND: The identification of genomic biomarkers is a key step towards improving diagnostic tests and therapies. We present a reference-free method for this task that relies on a k-mer representation of genomes and a machine learning algorithm that produces intelligible models. The method is computationally scalable and well-suited for whole genome sequencing studies. RESULTS: The method was validated by generating models that predict the antibiotic resistance of C. difficile, M. tuberculosis, P. aeruginosa, and S. pneumoniae for 17 antibiotics. The obtained models are accurate, faithful to the biological pathways targeted by the antibiotics, and they provide insight into the process of resistance acquisition. Moreover, a theoretical analysis of the method revealed tight statistical guarantees on the accuracy of the obtained models, supporting its relevance for genomic biomarker discovery. CONCLUSIONS: Our method allows the generation of accurate and interpretable predictive models of phenotypes, which rely on a small set of genomic variations. The method is not limited to predicting antibiotic resistance in bacteria and is applicable to a variety of organisms and phenotypes. Kover, an efficient implementation of our method, is open-source and should guide biological efforts to understand a plethora of phenotypes ( http://github.com/aldro61/kover/ ). PMID- 27671091 TI - Introduction. PMID- 27671092 TI - 33rd Annual Symposium on Nonhuman Primate Models for AIDS. PMID- 27671089 TI - Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg Strauss). AB - OBJECTIVE: To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. METHODS: Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. RESULTS: The study population included 157 patients (mean age 49.4+/-14.1), with a follow-up of 7.4+/-6.4years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p=0.005) and with the presence of ANCA (p<0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p=0.02) and renal disease (p=0.024), had higher peripheral eosinophilia (p=0.027), and a trend towards less myocarditis (p=0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. CONCLUSION: We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations. PMID- 27671093 TI - Large Area Fabrication of Semiconducting Phosphorene by Langmuir-Blodgett Assembly. AB - Phosphorene is a recently new member of the family of two dimensional (2D) inorganic materials. Besides its synthesis it is of utmost importance to deposit this material as thin film in a way that represents a general applicability for 2D materials. Although a considerable number of solvent based methodologies have been developed for exfoliating black phosphorus, so far there are no reports on controlled organization of these exfoliated nanosheets on substrates. Here, for the first time to the best of our knowledge, a mixture of N-methyl-2-pyrrolidone and deoxygenated water is employed as a subphase in Langmuir-Blodgett trough for assembling the nanosheets followed by their deposition on substrates and studied its field-effect transistor characteristics. Electron microscopy reveals the presence of densely aligned, crystalline, ultra-thin sheets of pristine phosphorene having lateral dimensions larger than hundred of microns. Furthermore, these assembled nanosheets retain their electronic properties and show a high current modulation of 104 at room temperature in field-effect transistor devices. The proposed technique provides semiconducting phosphorene thin films that are amenable for large area applications. PMID- 27671095 TI - Long-Term Follow-Up for a Giant Basilar Trunk Aneurysm Surgically Treated by Proximal Occlusion and External Carotid Artery to Posterior Cerebral Artery Bypass Using a Saphenous Vein Graft. AB - The authors describe a case of a basilar trunk aneurysm with long-term follow-up after successful bypass and proximal occlusion. A 64-year-old woman had a giant aneurysm of the basilar trunk and underwent external carotid artery-to-posterior cerebral artery vein graft bypass surgery and proximal clipping of the basilar artery, which was followed by low-dose aspirin (100 mg/d) treatment. No ischemic symptoms and lesions developed and the thrombosed aneurysm was stable during 11 years of follow-up. An extracranial-intracranial high flow bypass combined with immediate proximal occlusion and aspirin administration may be an acceptable treatment option for patients with giant posterior circulation aneurysms. PMID- 27671096 TI - Outcome of Repeated Thrombolysis in Debrecen Thrombolysis Database. AB - INTRODUCTION: Recombinant tissue plasminogen activator (rtPA) is an efficient therapy of acute ischemic stroke. The risk of a recurrent ischemic stroke is high. This prospective single center study aimed to assess whether or not the repeated rtPA treatment is beneficial for acute stroke patients. METHODS: All thrombolysed patients' data at the Department of Neurology, University of Debrecen have been recorded in the Debrecen Thrombolysis Database (DTD) since 2004. We identified 21 patients with repeated thrombolysis. Stroke severity by the NIH stroke scale score (NIHSSS) and imaging findings by the Alberta Stroke Programme Early CT Score were evaluated on admission and 1 day later. The modified Rankin Scale score at 3 months and case fatality at 1 year were evaluated. We compared the first and second thrombolyses, and we screened for bleeding and allergic reactions to determine safety. RESULTS: Within the 27-month median time, 18 patients were thrombolysed twice, with complete follow-up. In recurrent stroke patients, diabetes mellitus, congestive heart failure, and anticoagulation were more common. Admission cholesterol levels were decreased. After the first and second treatments, 24-hour NIHSSS were 3 (1;6) and 7 (1;10), respectively. At 3 months, good outcome was significantly higher after the first treatment than those of DTD, with no differences between the 2 attempts. There was little difference in 3-month and 1-year outcomes, regardless of laterality ipsilateral or contralateral hemisphere-in recurrent strokes. One patient had nonsymptomatic intracranial bleeding after repeated rtPA treatment. DISCUSSION: Recurrent rtPA treatment may be safe and effective in patients who have mild or moderate residual symptoms after the index stroke. PMID- 27671094 TI - A guide to the 3D structure of the ryanodine receptor type 1 by cryoEM. AB - Signal transduction by the ryanodine receptor (RyR) is essential in many excitable cells including all striated contractile cells and some types of neurons. While its transmembrane domain is a classic tetrameric, six transmembrane cation channel, the cytoplasmic domain is uniquely large and complex, hosting a multiplicity of specialized domains. The overall outline and substructure readily recognizable by electron microscopy make RyR a geometrically well-behaved specimen. Hence, for the last two decades, the 3D structural study of the RyR has tracked closely the technological advances in electron microscopy, cryo-electron microscopy (cryoEM), and computerized 3D reconstruction. This review summarizes the progress in the structural determination of RyR by cryoEM and, bearing in mind the leap in resolution provided by the recent implementation of direct electron detection, analyzes the first near-atomic structures of RyR. These reveal a complex orchestration of domains controlling the channel's function, and help to understand how this could break down as a consequence of disease-causing mutations. PMID- 27671097 TI - The Sex, Age, Medical History, Treatment, Tobacco Use, Race Risk (SAMe TT2R2) Score Predicts Warfarin Control in a Singaporean Population. AB - BACKGROUND: Warfarin reduces stroke risk in atrial fibrillation (AF) patients but requires ongoing monitoring. Time in therapeutic range (TTR) is used as a measure of warfarin control, with a TTR less than 60% associated with adverse patient outcomes. The Sex, Age, Medical history, Treatment, Tobacco use, Race (SAMe TT2R2) score has been identified as a model able to predict warfarin control, but this has been tested in mainly Caucasian populations. Therefore, the aim of this study was to determine the ability of the SAMe-TT2R2 score to predict warfarin control in a Singaporean population consisting of Chinese, Malay, and Indian race. METHODS: Retrospective data were collected from the National Heart Centre Singapore for AF patients receiving warfarin between January and June 2014. The TTR and the SAMe-TT2R2 score were calculated for each patient. RESULTS: The 1137 non-valvular AF patients had a mean TTR of 58.0 +/- 34.3% and a median SAMe-TT2R2 score of 3. The categorized SAMe-TT2R2 scores (2 versus >2) showed a significant reduction in mean TTR for the entire population (63.2% versus 55.8%, P = .0004) and also when categorized according to race for Chinese (62.7% versus 56.9%, P = .0075) and Malay (68.4% versus 50.6%, P = .0131) populations. CONCLUSION: The SAMe-TT2R2 tool is effective in predicting warfarin control in a Singaporean population as patients with a score greater than 2 had poor control. The minimum score for non-Caucasian patients is 2; thus, in these patients, the presence of any additional risk factors identified in the SAMe-TT2R2 tool categorizes them as unlikely to achieve adequate warfarin control and possible candidates for alternative anticoagulants. PMID- 27671098 TI - Potential use of saliva samples to diagnose Zika virus infection. PMID- 27671099 TI - Public reporting and the quality of care of German nursing homes. AB - OBJECTIVES: Since 2009, German nursing homes have been evaluated regularly by an external institution with quality report cards published online. We follow recent debates and argue that most of the information in the report cards does not reliably measure quality of care. However, a subset of up to seven measures does. Do these measures that reflect "risk factors" improve over time? METHOD: Using a sample of more than 3000 German nursing homes with information on two waves, we assume that the introduction of public reporting is an exogenous institutional change and apply before-after-estimations to obtain estimates for the relation between public reporting and quality. RESULTS: We find a significant improvement of the identified risk factors. Also, the two employed outcome quality indicators improve significantly. The improvements are driven by nursing homes with low quality in the first evaluation. CONCLUSION: To the extent that this can be interpreted as evidence that public reporting positively affects the (reported) quality in nursing homes, policy makers should carefully choose indicators reflecting care-sensitive quality. PMID- 27671100 TI - Clinicopathological differences between familial colorectal cancer type X and sporadic cancer in an isolated area of spain. AB - AIM: Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X (FCCTX) with those of sporadic colorectal cancer (S-CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S-CRC in patients from a historically isolated geographical region. METHOD: A retrospective study was carried out of patients with S-CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer (CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. RESULTS: Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S-CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S-CRC (64.06 +/- 12.65 years vs 69.13 +/- 10.80 years; P = 0.01; Z = -2.48). Patients with FCCTX had a larger number of synchronous tumours (P = 0.09). Recurrence was significantly higher in FCCTX than in S-CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC (P = 0.04; OR: 1.368, 95% CI: 1.01-1.84, and P = 0.04; OR: 1.363, 95% CI: 1.08-1.65) and with the total number of cases of CRC in the immediate family (P < 0.01; OR: 1.377, 95% CI: 1.17-1.61). Recurrence-free time was significantly lower in patients with FCCTX (log-rank = 0.01). CONCLUSION: Significant differences were found in several demographic and clinicopathological variables between patients with FCCTX and patients with S-CRC. These included increased tumour presentation under the age of 50 years and a higher recurrence rate in patients with FCCTX, suggesting an increased risk of CRC in this group. PMID- 27671101 TI - Real-life use of digoxin in patients with non-valvular atrial fibrillation: data from the RAMSES study. AB - WHAT IS KNOWN AND OBJECTIVE: Although inappropriate use of digoxin has been described in various populations, a real-world evaluation of patterns of digoxin prescription has not been well studied in patients with atrial fibrillation (AF). The aim of this study was to identify prevalence, indications and appropriateness of digoxin use in the general population of patients with non-valvular AF (NVAF) in Turkey. METHODS: We included and classified patients from the RAMSES (ReAl life Multicentre Survey Evaluating Stroke prevention strategies in Turkey) study, a prospective registry including 6273 patients with NVAF, on the basis of digoxin use. After excluding the data of 73 patients whose medical history about digoxin use or left ventricle function was absent, 6200 patients were included for the final analysis. Digoxin use was considered inappropriate if patients did not have left ventricular systolic dysfunction or symptomatic heart failure (HF). RESULTS AND DISCUSSION: Digoxin was used in 1274 (20.5%) patients. Patients treated with digoxin were older (71.4 +/- 9.8 years vs. 69.2 +/- 10.9 years, P < 0.001), more likely to be female (58.8% vs. 55.9%, P = 0.019) and had more common comorbidities such as HF (40.2% vs. 17.4%), diabetes (26.4% vs. 21.1%), coronary artery disease (35.3 vs. 27.6%) and persistent/permanent AF (93.4% vs. 78.4%; P < 0.001 for each comparison). Of the 1274 patients, the indication of digoxin use was considered inappropriate in 762 (59.8%). WHAT IS NEW AND CONCLUSION: Our findings show that nearly one-fifth of the patients with NVAF were on digoxin therapy and nearly 60% of these patients were receiving digoxin with inappropriate indications in a real-world setting. PMID- 27671102 TI - Eltrombopag (thrombopoietin-receptor agonist) and plasmapheresis as rescue therapy of acute post-renal transplant immune thrombocytopenia in a child with Schimke immuno-osseous dysplasia-case report. AB - SIOD is rare disorder related to SMARCAL1 or SMARCAL2 gene mutation, including (among other comorbidities) T-cell immunodeficiency, nephrotic syndrome, and renal failure. Up to 22% of primary patients may develop various autoimmune disorders. We report the case of 11-year-old male with SIOD, who presented ITP at 2 years after renal transplantation with decrease in platelet count (from normal) to 56 000/MUL and then (gradually) to 2000/MUL. There was no effect of iv. methylprednisolone/dexamethasone. As the presence of antibodies against GPIIb/IIIa, GPIb, and GPIaIIa platelet glycoproteins was confirmed, patient was given 50 g of IVIG and then was put on plasmapheresis; however, both showed poor direct effect. As we were afraid to give rituximab (due to expected overimmunosuppression), we prescribed the oral TPO-receptor agonist (eltrombopag). Patient responded after 17 days of therapy, to the final dose of 50 mg/d (approx. 2 mg/kg). The antiplatelet antibodies disappeared after four plasmapheresis. Overall, the therapy was continued for 7 weeks and was stopped at platelet count of 433 000/MUL. Platelet count remained stable in 8-month follow up. Combination of plasmapheresis and TPO-receptor agonist was effective in post renal transplant acute ITP in patient with SIOD. PMID- 27671103 TI - Probing the global kinome and phosphoproteome in Chlamydomonas reinhardtii via sequential enrichment and quantitative proteomics. AB - The identification of dynamic protein phosphorylation events is critical for understanding kinase/phosphatase-regulated signaling pathways. To date, protein phosphorylation and kinase expression have been examined independently in photosynthetic organisms. Here we present a method to study the global kinome and phosphoproteome in tandem in a model photosynthetic organism, the alga Chlamydomonas reinhardtii (Chlamydomonas), using mass spectrometry-based label free proteomics. A dual enrichment strategy targets intact protein kinases via capture on immobilized multiplexed inhibitor beads with subsequent proteolytic digestion of unbound proteins and peptide-based phosphorylation enrichment. To increase depth of coverage, both data-dependent and data-independent (via SWATH, Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra) mass spectrometric acquisitions were performed to obtain a more than 50% increase in coverage of the enriched Chlamydomonas kinome over coverage found with no enrichment. The quantitative phosphoproteomic dataset yielded 2250 phosphopeptides and 1314 localized phosphosites with excellent reproducibility across biological replicates (90% of quantified sites with coefficient of variation below 11%). This approach enables simultaneous investigation of kinases and phosphorylation events at the global level to facilitate understanding of kinase networks and their influence in cell signaling events. PMID- 27671104 TI - Antibacterial and osteo-stimulatory effects of a borate-based glass series doped with strontium ions. AB - This work considered the effect of both increasing additions of Strontium (Sr2+) and incubation time on solubility and both antibacterial and osteo-stimulatory effects of a series of glasses based on the B2O3-P2O5-CaCO3-Na2CO3-TiO2-SrCO3 series. The amorphous nature of all the glasses was confirmed by X-ray diffraction. Discs of each glass were immersed in de-ionized water for 1, 7 and 30 days, and the water extracts were used for ion release profiles, pH measurements and cytotoxicity testing. Atomic absorption spectroscopy was employed to detect the release of Na+, Ca2+ and Sr2+ ions from the glasses with respect to maturation, which indicated that the addition of Sr2+ retarded solubility of the glass series. This effect was also confirmed by weight loss analysis through comparing the initial weight of glass discs before and after periods of incubation. The incorporation of Sr2+ in the glasses did not influence the pH of the water extracts when the glasses were stored for up to 30 days. Cytotoxicity testing with an osteoblastic cell line (MC3T3-E1) indicated that glasses with the higher (20 mol% and 25 mol%) Sr2+ incorporation promoted proliferation of osteoblast cells, while the glasses with lower Sr2+ contents inhibited cell growth. The glass series, except for Ly-B5 (which contained the highest Sr2+ incorporation; 25 mol%), were bacteriostatic against S. aureus in the short term (1-7 days) as a result of the dissolution products released. PMID- 27671105 TI - Sagittal Plane Postural Changes in Female Patients with Breast Cancer after Different Surgical Techniques. PMID- 27671106 TI - Reproductive switching analysis of Daphnia similoides between sexual female and parthenogenetic female by transcriptome comparison. AB - The water flea Daphnia are planktonic crustaceans commonly found in freshwater environment that can switch their reproduction mode from parthenogenesis to sexual reproduction to adapt to the external environment. As such, Daphnia are great model organisms to study the mechanism of reproductive switching, the underlying mechanism of reproduction and development in cladocerans and other animals. However, little is known about the Daphnia's reproductive behaviour at a molecular level. We constructed a genetic database of the genes expressed in a sexual female (SF) and a parthenogenetic female (PF) of D. similoides using Illumina HiSeq 2500. A total of 1,763 differentially expressed genes (865 up- and 898 down-regulated) were detected in SF. Of the top 30 up-regulated SF unigenes, the top 4 unigenes belonged to the Chitin_bind_4 family. In contrast, of the top down-regulated SF unigenes, the top 3 unigenes belonged to the Vitellogenin_N family. This is the first study to indicate genes that may have a crucial role in reproductive switching of D. similoides, which could be used as candidate genes for further functional studies. Thus, this study provides a rich resource for investigation and elucidation of reproductive switching in D. similoides. PMID- 27671107 TI - Detection of the designer benzodiazepine metizolam in urine and preliminary data on its metabolism. AB - Designer benzodiazepines provide an attractive alternative to prescribed benzodiazepines for abuse purposes as they are readily available via the Internet without control. Metizolam was ordered via the Internet and a 2 mg blue tablet was orally administered to a 54-year-old man. Urine samples were collected over 6 days in polypropylene tubes. After liquid/liquid extraction at pH 9.5, metizolam was analyzed by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) using a standard method devoted to benzodiazepines, and ions transitions, at m/z 328.9 > 275.0 and 328.9 > 300.0. Metizolam was detectable in hydrolyzed urine during the 46-h period, with concentrations always lower than 11 ng/mL. About 0.3% of the initial dose was excreted in urines as total unchanged metizolam during the first 24 h. The most relevant potential CYP- and UGT-dependent metabolites of metizolam were investigated in vitro using human liver microsome incubation and, subsequently, liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS) analysis. Three mono-hydroxylated metabolites were produced including a hydroxylation compound at the 2-ethyl moiety of metizolam (M1) as quantitatively main metabolite, and a N-hydroxymetiazolam (M2). The structure of the third metabolite (M3) could not be elucidated because of a too low experimental production rate. Two authentic urine samples were analyzed using the same analytical method to search for metabolites of metizolam. M1, together with its glucuronide (M1-Glu), and M2 were observed in urine at the 8 h mark, whereas only M1 and M1-Glu were still detected in urine at 30 h post administration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27671108 TI - Antigen-Specific Immune Modulation Targets mTORC1 Function To Drive Chemokine Receptor-Mediated T Cell Tolerance. AB - To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells. Indeed, Ag administration induces upregulation of programmed death-ligand 1 on dendritic cells in a T cell-dependent manner. In return, programmed death-ligand 1 interacts with the constitutively expressed programmed death-1 on the target T cells and stimulates docking of Src homology 2 domain-containing tyrosine phosphatase 2 phosphatase to the cytoplasmic tail of programmed death-1. Active Src homology 2 domain-containing tyrosine phosphatase 2 impairs the signaling function of the PI3K/protein kinase B (AKT) pathway, leading to functional defect of mTORC1, downregulation of CXCR3 expression, and suppression of T1D. Thus, mTORC1 component of the metabolic pathway serves as a target for chemokine receptor-mediated T cell tolerance and suppression of T1D. PMID- 27671109 TI - Antigen-Specific Development of Mucosal Foxp3+RORgammat+ T Cells from Regulatory T Cell Precursors. AB - Foxp3+retinoic acid-related orphan receptor (ROR)gammat+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relationship to RORgammat regulatory T and Th17 cells remain unclear. In this study, we use a fixed TCRbeta system to show that the TCR repertoire of the Foxp3+RORgammat+ population is mostly distinct compared with other colonic T cell subsets. However, of these TCRs, a fraction is also found in the Th17 subset, suggesting that TCR repertoire overlap may contribute to the reported ability of Foxp3+RORgammat+ cells to regulate Th17 immunity. Naive transgenic T cells expressing a Foxp3+RORgammat+ restricted TCR first acquire a Foxp3+RORgammat- phenotype before coexpressing RORgammat, suggesting that Foxp3+RORgammat+ cell development can occur via an RORgammat- regulatory T cell intermediate. PMID- 27671110 TI - Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination. AB - It has been difficult to translate promising results from DNA vaccination in mice to larger animals and humans. Previously, DNA vaccines encoding proteins that target Ag to MHC class II (MHC-II) molecules on APCs have been shown to induce rapid, enhanced, and long-lasting Ag-specific Ab titers in mice. In this study, we describe two novel DNA vaccines that as proteins target HLA class II (HLA-II) molecules. These vaccine proteins cross-react with MHC-II molecules in several species of larger mammals. When tested in ferrets and pigs, a single DNA delivery with low doses of the HLA-II-targeted vaccines resulted in rapid and increased Ab responses. Importantly, painless intradermal jet delivery of DNA was as effective as delivery by needle injection followed by electroporation. As an indication that the vaccines could also be useful for human application, HLA-II-targeted vaccine proteins were found to increase human CD4+ T cell responses by a factor of *103 in vitro. Thus, targeting of Ag to MHC-II molecules may represent an attractive strategy for increasing efficacy of DNA vaccines in larger animals and humans. PMID- 27671112 TI - CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders. AB - A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. PMID- 27671111 TI - HIF-2alpha in Resting Macrophages Tempers Mitochondrial Reactive Oxygen Species To Selectively Repress MARCO-Dependent Phagocytosis. AB - Hypoxia-inducible factor (HIF)-alpha isoforms regulate key macrophage (MPhi) functions during ischemic inflammation. HIF-2alpha drives proinflammatory cytokine production; however, the requirements for HIF-2alpha during other key MPhi functions, including phagocytosis, are unknown. In contrast to HIF-1alpha, HIF-2alpha was not required for hypoxic phagocytic uptake. Surprisingly, basal HIF-2alpha levels under nonhypoxic conditions were necessary and sufficient to suppress phagocytosis. Screening approaches revealed selective induction of the scavenger receptor MARCO, which was required for enhanced engulfment. Chromatin immunoprecipitation identified the antioxidant NRF2 as being directly responsible for inducing Marco Concordantly, Hif-2alpha-/- MPhis exhibited reduced antioxidant gene expression, and inhibition of mitochondrial reactive oxygen species suppressed Marco expression and phagocytic uptake. Ex vivo findings were recapitulated in vivo; the enhanced engulfment phenotype resulted in increased bacterial clearance and cytokine suppression. Importantly, natural induction of Hif-2alpha by IL-4 also suppressed MARCO-dependent phagocytosis. Thus, unlike most characterized prophagocytic regulators, HIF-2alpha can act as a phagocytic repressor. Interestingly, this occurs in resting MPhis through tempering of steady-state mitochondrial reactive oxygen species. In turn, HIF-2alpha promotes MPhi quiescence by blocking a MARCO bacterial-response pathway. IL-4 also drives HIF-2alpha suppression of MARCO, leading to compromised bacterial immunosurveillance in vivo. PMID- 27671113 TI - Genome assembly and annotation of Arabidopsis halleri, a model for heavy metal hyperaccumulation and evolutionary ecology. AB - The self-incompatible species Arabidopsis halleri is a close relative of the self compatible model plant Arabidopsis thaliana. The broad European and Asian distribution and heavy metal hyperaccumulation ability make A. halleri a useful model for ecological genomics studies. We used long-insert mate-pair libraries to improve the genome assembly of the A. halleri ssp. gemmifera Tada mine genotype (W302) collected from a site with high contamination by heavy metals in Japan. After five rounds of forced selfing, heterozygosity was reduced to 0.04%, which facilitated subsequent genome assembly. Our assembly now covers 196 Mb or 78% of the estimated genome size and achieved scaffold N50 length of 712 kb. To validate assembly and annotation, we used synteny of A. halleri Tada mine with a previously published high-quality reference assembly of a closely related species, Arabidopsis lyrata. Further validation of the assembly quality comes from synteny and phylogenetic analysis of the HEAVY METAL ATPASE4 (HMA4) and METAL TOLERANCE PROTEIN1 (MTP1) regions using published sequences from European A. halleri for comparison. Three tandemly duplicated copies of HMA4, key gene involved in cadmium and zinc hyperaccumulation, were assembled on a single scaffold. The assembly will enhance the genomewide studies of A. halleri as well as the allopolyploid Arabidopsis kamchatica derived from A. lyrata and A. halleri. PMID- 27671115 TI - Bullous Scabies in a 5-Year-Old Child. PMID- 27671116 TI - Apples and Oranges: Serious Chronic Illness in Adults and Children. PMID- 27671117 TI - Early Diagnosis in Dedicator of Cytokinesis 8 (DOCK8) Deficiency. PMID- 27671114 TI - Preloading of Hydrophobic Anticancer Drug into Multifunctional Nanocarrier for Multimodal Imaging, NIR-Responsive Drug Release, and Synergistic Therapy. AB - Applications of hydrophobic drug-based nanocarriers (NCs) remain largely limited because of their low loading capacity. Here, development of a multifunctional hybrid NC made of a magnetic Fe3O4 core and a mesoporous silica shell embedded with carbon dots (CDs) and paclitaxel (PTX), and covered by another layer of silica is reported. The NC is prepared via a one-pot process under mild condition. The PTX loading method introduced in this study simplifies drug loading process and demonstrates a high loading capacity due to mesoporous silica dual-shell structure, supramolecular pi-stacking between conjugated rings of PTX molecules, and aromatic rings of the CDs in the hybrid NC. The CDs serve as both confocal and two-photon fluorescence imaging probes, while the Fe3O4 core serves as a magnetic resonance imaging contrast agent. Significantly, NC releases PTX in response to near infrared irradiation as a result of local heating of the embedded CDs and the heating of CDs also provides an additional therapeutic effect by thermally killing cancer cells in tumor in addition to the chemotherapeutic effect of released PTX. Both in vitro and in vivo results show that NC demonstrates high therapeutic efficacy through a synergistic effect from the combined chemo-photothermal treatments. PMID- 27671118 TI - HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix. AB - Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPsigma (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID- 27671119 TI - Promotion and Persistence of HIV Testing and HIV/AIDS Knowledge: Evidence From a Randomized Controlled Trial in Ethiopia. AB - We use data from a randomized controlled trial in Ethiopia and examine the causal effects of HIV/AIDS education, home-based voluntary HIV counseling and testing (VCT), and conditional cash transfers (CCT) for facility-based VCT on HIV/AIDS knowledge and demand for HIV testing. HIV/AIDS education significantly increases HIV/AIDS knowledge but has a limited effect on testing take-up. However, when HIV/AIDS education is combined with either home-based VCT or CCT for facility based VCT, take-up increases substantially by about 63 and 57 percentage points, respectively. We also demonstrate evidence of persistence in test-taking behavior, where past HIV testing does not dampen demand for testing. Lastly, we find suggestive evidence that home-based VCT could be more effective at detecting HIV-positive cases relative to CCT for facility-based VCT. Our findings highlight the importance of geographic accessibility in the testing decision and persistence in demand for HIV testing. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27671120 TI - Ethylene Biosynthesis and Signaling Is Required for Rice Immune Response and Basal Resistance Against Magnaporthe oryzae Infection. AB - Recent studies have suggested that ethylene enhances host resistance to fungal pathogen Magnaporthe oryzae, the causal agent of rice blast disease. Among the six 1-aminocyclopropane-1-carboxylic acid synthase genes in rice, OsACS1 and OsACS2 are induced within 24 h of inoculation by M. oryzae. This induction occurs simultaneously with an increase in ethylene production that is noticeable 12 h postinoculation. The purpose of this study was to examine the dynamics of ethylene production and signaling in wild type and RNA interference-mediated suppression lines deficient in ethylene production (acs2) or signaling (eil1) after challenge with M. oryzae as well as fungal cell-wall elicitors. Ethylene insensitive mutant lines show an attenuated basal defense response including lower basal expression of the genes encoding a chitin-binding receptor, pathogenesis-related (PR) proteins, and the enzymes involved in the synthesis of diterprenoid phytoalexins, a reduction on early hypersensitive response (HR)-like cell death, and reduced incidence of callose deposition. Ethylene-deficient mutants showed an intermediate phenotype, with a significant reduction in expression of defense-related genes and callose deposition, but only a slight reduction in HR-like cell death. As a result, all ethylene-insensitive mutants show increased susceptibility to M. oryzae, whereas the ethylene-deficient lines show a slight but less significant increase in disease severity. These results show that ethylene signaling and, to some extent, ethylene production are required for rice basal resistance against the blast fungus Magnaporthe oryzae. PMID- 27671121 TI - PvPGIP2 Accumulation in Specific Floral Tissues But Not in the Endosperm Limits Fusarium graminearum Infection in Wheat. AB - Fusarium head blight (FHB) caused by Fusarium graminearum is one of the most destructive fungal diseases of wheat worldwide. The pathogen infects the spike at flowering time and causes severe yield losses, deterioration of grain quality, and accumulation of mycotoxins. The understanding of the precise means of pathogen entry and colonization of floral tissue is crucial to providing effective protection against FHB. Polygalacturonase (PG) inhibiting proteins (PGIPs) are cell-wall proteins that inhibit the activity of PGs, a class of pectin-depolymerizing enzymes secreted by microbial pathogens, including Fusarium spp. The constitutive expression of a bean PGIP (PvPGIP2) limits FHB symptoms and reduces mycotoxin accumulation in wheat grain. To better understand which spike tissues play major roles in limiting F. graminearum infection, we explored the use of PvPGIP2 to defend specific spike tissues. We show here that the simultaneous expression of PvPGIP2 in lemma, palea, rachis, and anthers reduced FHB symptoms caused by F. graminearum compared with symptoms in infected nontransgenic plants. However, the expression of PvPGIP2 only in the endosperm did not affect FHB symptom development, indicating that once the pathogen has reached the endosperm, inhibition of the pathogen's PG activity is not effective in preventing its further spread. PMID- 27671122 TI - Devitalisation of human cartilage by high hydrostatic pressure treatment: Subsequent cultivation of chondrocytes and mesenchymal stem cells on the devitalised tissue. AB - The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair. PMID- 27671123 TI - Concussion and its neurobehavioural sequelae. AB - A concussion results from a force to the brain that results in a transient loss of connectivity within the brain. Sport psychiatrists are increasingly called to be part of the concussion team and need to be prepared to manage issues related to concussion and its behavioural sequelae. Objectively, the best evidence available suggests that deficits in attention and/or in balance are the most reliable objective findings that a concussion has occurred. Prognosis after a concussion is generally very good, although a sub-set of patients that are yet well defined seem pre-disposed to delayed recovery. Neither head CT nor MRI are sufficiently sensitive to diagnose the type of injuries that pre-dispose patients to the neurobehavioural sequelae that have been associated with a concussion; confounding this is the finding that many of these signs and symptoms associated with concussion occur in other types of non-head injuries. Brain biomarkers and functional MRI (fMRI) hold promise in both diagnosis and prognosis of concussion, but are still research tools without validated clinical utility at this time. Finally, neurocognitive testing holds promise as a diagnostic criterion to demonstrate injury but, unfortunately, these tests are also limited in their prognostic utility and are of limited value. PMID- 27671124 TI - Multiple sclerosis and employment: Associations of psychological factors and work instability. AB - BACKGROUND: People with multiple sclerosis often stop working earlier than expected. Psychological factors may have an impact on job retention. Investigation may inform interventions to help people stay in work. OBJECTIVE: To investigate the associations between psychological factors and work instability in people with multiple sclerosis. METHODS: A multi-method, 2-phased study. Focus groups were held to identify key themes. Questionnaire packs using validated scales of the key themes were completed at baseline and at 8-month follow-up. RESULTS: Four key psychological themes emerged. Out of 208 study subjects 57.2% reported medium/high risk of job loss, with marginal changes at 8 months. Some psychological variables fluctuated significantly, e.g. depression fell from 24.6% to 14.5%. Work instability and anxiety and depression were strongly correlated (chi2 p < 0.001). Those with probable depression at baseline had 7.1 times increased odds of medium/high work instability, and baseline depression levels also predicted later work instability (Hosmer-Lemeshow test 0.899; Nagelkerke R Square 0.579). CONCLUSION: Psychological factors fluctuated over the 8-month follow-up period. Some psychological variables, including anxiety and depression, were significantly associated with, and predictive of, work instability. Longitudinal analysis should further identify how these psychological attributes impact on work instability and potential job loss in the longer term. PMID- 27671126 TI - What's Wrong with Sex Education? AB - Sex education is supposed to provide young people with knowledge and understanding but much of its seems to be moral propaganda with a thin veneer of liberality. PMID- 27671127 TI - Making Sense of the Short-Hand. AB - When a patient complains of 'nerves' a doctor is immediately in the business of interpretation and 'reading between the lines'. PMID- 27671128 TI - Verdicts on the High Life. AB - People rehoused in tower blocks are usually glad to be out of sub-standard housing but may soon long for the way of life that died when tenements and terraces were demolished. PMID- 27671129 TI - Scan. AB - A personal view of the social services. PMID- 27671125 TI - Evolution of Protein Domain Repeats in Metazoa. AB - Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. KEY WORDS: protein evolution, domain rearrangements, protein repeats, concerted evolution. PMID- 27671130 TI - Finding the Real You. AB - Everyone has to sift through influences and affectations before settling into their enduring 'identity, but is there really a single 'Crisis' involved or is it a gradual process of discovery and self-acceptance? PMID- 27671132 TI - News Review. PMID- 27671131 TI - Living with Schizophrenia. AB - It seems that, as far as the authorities are concerned, a schizophrenic is either ill enough to be under a compulsory order or he is a fully responsible adult with whom they can deal directly. In reality he is neither, but a mentally-handicapped person in need of care and protection. PMID- 27671133 TI - To Preserve Innocence. AB - Scapegoats have always served to underline the standards of the majority, a new book suggests that society in the 19th and 20th centuries has used the mentally ill as the outcasts necessary to confirm its stability and righteousness. PMID- 27671134 TI - From Where I Sit: Editorial Comment. PMID- 27671135 TI - Right of Reply. AB - The 'Laingian' concept of psychiatry seems to have effectively 'captured' the media and 'conventional' psychiatry is rapidly becoming a 'silent ogre'-perhaps more doctors should be putting their case before patients become too reluctant to come forward for treatment. PMID- 27671136 TI - Cared for and Caring. AB - Being mentally handicapped doesn't relieve people of their capacity for emotion, tenderness and concern. In hospital they should still be able to experience the pleasures and annoyances of ordinary 'family' life to the greatest extent possible. PMID- 27671137 TI - Letters. PMID- 27671138 TI - Letters. PMID- 27671139 TI - Papering over the Cracks. AB - Beyond the limelight of teaching hospitals, the psychiatric profession is in a state of near-collapse. A lack of resources and man-power is resulting in an incomplete service which is unfair to patients and demoralising for doctors-the situation needs salvaging, and soon. PMID- 27671140 TI - Culture-independent study of bacterial communities in tropical river sediment. AB - Ubiquitous microbial communities in river sediments actively govern organic matter decomposition, nutrient recycling, and remediation of toxic compounds. In this study, prokaryotic diversity in two major rivers in central Thailand, the Chao Phraya (CP) and the Tha Chin (TC) distributary was investigated. Significant differences in sediment physicochemical properties, particularly silt content, were noted between the two rivers. Tagged 16S rRNA sequencing on a 454 platform showed that the sediment microbiomes were dominated by Gammaproteobacteria and sulfur/sulfate reducing Deltaproteobacteria, represented by orders Desulfobacteriales and Desulfluromonadales together with organic degraders Betaproteobacteria (orders Burkholderiales and Rhodocyclales) together with the co-existence of Bacteroidetes predominated by Sphingobacteriales. Enrichment of specific bacterial orders was found in the clayey CP and silt-rich TC sediments, including various genera with known metabolic capability on decomposition of organic matter and xenobiotic compounds. The data represent one of the pioneered works revealing heterogeneity of bacteria in river sediments in the tropics. PMID- 27671141 TI - Effects of Particle Size on the Attenuated Total Reflection Spectrum of Minerals. AB - This study focuses on particle size effect on monomineralic powders recorded using attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy. Six particle size fractions of quartz, feldspar, calcite, and dolomite were prepared (<2, 2-4, 4-8, 8-16, 16-32, and 32-63 um). It is found that the width, intensity, and area of bands in the ATR FT-IR spectra of minerals have explicit dependence on the particle size. As particle size increases, the intensity and area of IR bands usually decrease while the width of bands increases. The band positions usually shifted to higher wavenumbers with decreasing particle size. Infrared spectra of minerals are the most intensive in the particle size fraction of 2-4 um. However, if the particle size is very small (<2 um), due to the wavelength and penetration depth of the IR light, intensity decreases. Therefore, the quantity of very fine-grained minerals may be underestimated compared to the coarser phases. A nonlinear regression analysis of the data indicated that the average coefficients and indices of the power trend line equation imply a very simplistic relationship between median particle diameter and absorbance at a given wavenumber. It is concluded that when powder samples with substantially different particle size are compared, as in regression analysis for modal predictions using ATR FT-IR, it is also important to report the grain size distribution or surface area of samples. The band area of water (3000-3620 cm-1) is similar in each mineral fraction, except for the particles below 2 um. It indicates that the finest particles could have disproportionately more water adsorbed on their larger surface area. Thus, these higher wavenumbers of the ATR FT-IR spectra may be more sensitive to this spectral interference if the number of particles below 2 um is considerable. It is also concluded that at least a proportion of the moisture could be very adhesive to the particles due to the band shift towards lower wavenumbers in the IR range of 3000-3620 cm-1. PMID- 27671142 TI - Prediction of the Ultraviolet-Visible Absorption Spectra of Polycyclic Aromatic Hydrocarbons (Dibenzo and Naphtho) Derivatives of Fluoranthene. AB - The annellation theory method has been used to predict the locations of maximum absorbance (LMA) of the ultraviolet-visible (UV-Vis) spectral bands in the group of polycyclic aromatic hydrocarbons (PAHs) C24H14 (dibenzo and naphtho) derivatives of fluoranthene (DBNFl). In this group of 21 PAHs, ten PAHs present a sextet migration pattern with four or more benzenoid rings that is potentially related to a high molecular reactivity and high mutagenic conduct. This is the first time that the locations of maximum absorbance in the UV-Vis spectra of naphth[1,2- a]aceanthrylene, dibenz[ a,l]aceanthrylene, indeno[1,2,3- de]naphthacene, naphtho[1,2- j]fluoranthene, naphth[2,1- e]acephenanthrylene, naphth[2,1- a]aceanthrylene, dibenz[ a,j]aceanthrylene, naphth[1,2- e]acephenanthrylene, and naphtho[2,1- j]fluoranthene have been predicted. Also, this represents the first report about the application of the annellation theory for the calculation of the locations of maximum absorbance in the UV-Vis spectra of PAHs with five-membered rings. Furthermore, this study constitutes the premier investigation beyond the pure benzenoid classical approach toward the establishment of a generalized annellation theory that will encompass not only homocyclic benzenoid and non-benzenoid PAHs, but also heterocyclic compounds. PMID- 27671143 TI - Population and hierarchy of active species in gold iron oxide catalysts for carbon monoxide oxidation. AB - The identity of active species in supported gold catalysts for low temperature carbon monoxide oxidation remains an unsettled debate. With large amounts of experimental evidence supporting theories of either gold nanoparticles or sub-nm gold species being active, it was recently proposed that a size-dependent activity hierarchy should exist. Here we study the diverging catalytic behaviours after heat treatment of Au/FeOx materials prepared via co-precipitation and deposition precipitation methods. After ruling out any support effects, the gold particle size distributions in different catalysts are quantitatively studied using aberration corrected scanning transmission electron microscopy (STEM). A counting protocol is developed to reveal the true particle size distribution from HAADF-STEM images, which reliably includes all the gold species present. Correlation of the populations of the various gold species present with catalysis results demonstrate that a size-dependent activity hierarchy must exist in the Au/FeOx catalyst. PMID- 27671144 TI - Radical Nephrectomy With or Without Lymph Node Dissection for Nonmetastatic Renal Cell Carcinoma: A Propensity Score-based Analysis. AB - BACKGROUND: It is uncertain whether lymph node dissection (LND) provides a therapeutic benefit in renal cell carcinoma (RCC). OBJECTIVE: To evaluate the association of LND with oncologic outcomes among patients undergoing radical nephrectomy (RN) for nonmetastatic RCC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 1797 patients treated with RN for M0 RCC between 1990 and 2010, including 606 (34%) who underwent LND. INTERVENTION: RN with or without LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The associations of LND with the development of distant metastases, cancer-specific mortality (CSM), and all-cause mortality (ACM) were evaluated using 1:1 propensity score (PS) matching, adjustment for/stratification by PS quintile, and inverse probability weighting. Cox models were used to evaluate the association of the number of lymph nodes removed with oncologic outcomes. RESULTS AND LIMITATIONS: A total of 111 (6.2%) patients were pN1. The median follow-up after surgery was 10.6 yr. Following PS adjustment, there were no significant differences in clinicopathologic features between patients with and without LND. In the overall cohort, LND was not significantly associated with a reduced risk of distant metastases, CSM, or ACM. Moreover, LND was not associated with improved oncologic outcomes even among patients at increased risk of pN1 disease, including those with preoperative radiographic lymphadenopathy, or across increasing threshold probabilities for pN1 disease from 0.05 to 0.50. Among patients who underwent LND, the extent of LND was not significantly associated with the development of distant metastases, CSM, or ACM. Limitations include the retrospective design. CONCLUSIONS: We did not identify an oncologic benefit to LND in the overall cohort or among patients at increased risk of nodal disease. These findings do not support a therapeutic benefit to LND in patients with M0 RCC. PATIENT SUMMARY: Lymph node dissection does not appear to provide a therapeutic benefit in patients with nonmetastatic renal cell carcinoma. PMID- 27671145 TI - Individuals that are consistent in risk-taking benefit during collective foraging. AB - It is well established that living in groups helps animals avoid predation and locate resources, but maintaining a group requires collective coordination, which can be difficult when individuals differ from one another. Personality variation (consistent behavioural differences within a population) is already known to be important in group interactions. Growing evidence suggests that individuals also differ in their consistency, i.e. differing in how variable they are over time, and theoretical models predict that this consistency can be beneficial in social contexts. We used three-spined sticklebacks (Gasterosteus aculeatus) to test whether the consistency in, as well as average levels of, risk taking behaviour (i.e. boldness) when individuals were tested alone affects social interactions when fish were retested in groups of 2 and 4. Behavioural consistency, independently of average levels of risk-taking, can be advantageous: more consistent individuals showed higher rates of initiating group movements as leaders, more behavioural coordination by joining others as followers, and greater food consumption. Our results have implications for both group decision making, as groups composed of consistent individuals are more cohesive, and personality traits, as social interactions can have functional consequences for consistency in behaviour and hence the evolution of personality variation. PMID- 27671146 TI - Collinearity and multivariable analysis: response to comments by Claret et al. PMID- 27671148 TI - GMC was wrong to release report on GP's competence to patient, rules judge. PMID- 27671147 TI - Collinearity and multivariable analysis. PMID- 27671149 TI - Metastasectomy for Metastatic Renal Cell Carcinoma (mRCC): Lucky Break or Evidence-Based Approach? PMID- 27671150 TI - Cervical lymph node metastases of squamous cell carcinoma of unknown origin: the diagnostic value of FDG PET/CT and clinical outcome. AB - FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of <=7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available. PMID- 27671152 TI - Balloon-Occluded Retrograde Transvenous Obliteration of a Gastric Vascular Malformation: An Innovative Approach to Treatment of a Rare Condition. AB - Arteriovenous malformations (AVMs) are a high-flow form of a vascular malformation, which can be found anywhere in the body. While historically treated surgically, a multidisciplinary approach utilizing multiple specialties and treatment modalities is now commonly employed. In order to effectively treat an AVM, the nidus must be targeted and eradicated, which can be done via multiple approaches. We present the case of a 43-year-old male with a gastric wall AVM, which was initially incompletely treated using a percutaneous transarterial approach. The gastric AVM was noted to have dominant drainage through a gastrorenal shunt; therefore, Balloon-occluded Retrograde Transvenous Obliteration (BRTO) was utilized to eradicate the AVM nidus. This case illustrates the utility of Interventional Radiology, specifically BRTO, as another treatment option for challenging AVMs. PMID- 27671151 TI - Differences in Patient Characteristics and Midterm Outcome Between Asian and European Patients Treated with Radiofrequency Ablation for Hepatocellular Carcinoma. AB - PURPOSE: The aim of this study was to compare patient characteristics and midterm outcomes after RFA for unresectable Hepatocellular carcinoma (HCC) in Asian and European cohorts. MATERIALS AND METHODS: The study was based on retrospective analysis of 279 patients (mean 64.8 +/- 12.1 years; 208 males) treated with RFA for de novo HCC in tertiary referral centers in Singapore and the Netherlands, with median follow-up of 28.2 months (quartiles: 13.1-40.5 months). Cumulative incidence of recurrence and death were analyzed using a competing risk model. RESULTS: Age was higher in the Asian group: 66.5 versus 60.1 years (p < 0.0001). The most common etiology was hepatitis B in the Asian group (48.0 %) and alcohol induced cirrhosis in Europeans (54.4 %); p < 0.001. Asian patients had less advanced disease: 35.5, 55.0, and 3.0 %, respectively, had BCLC 0, A, and B versus 21.5, 58.2, and 15.2 % in the European group (p = 0.01). The cumulative incidences of recurrence in the Asian group at 1, 2, 3, and 5 years were 37.0, 56.4, 62.3, and 67.7 %, respectively, compared to 32.6, 47.2, 49.7, and 53.4 % in the European group (p = 0.474). At 1, 2, 3, and 5 years, the cumulative incidence rates of death in the Asian group were 2.0, 3.9, 4.9, and 4.9 %, respectively, corresponding to 7.7, 9.2, 14.1, and 21.0 % in the European group (p = 0.155). CONCLUSION: Similar short-term treatment outcomes are achieved with RFA in HCC patients in the South-East Asian and Northern-European populations. Midterm recurrence and death rates differ between the groups as a result of differences in baseline patient characteristics and patient selection. Our study provides insight relevant to the design of future international studies. PMID- 27671153 TI - Percutaneous Intravascular Biopsy Using a Bronchoscopy Forceps Diagnosis of a Pulmonary Artery Intimal Sarcoma. PMID- 27671154 TI - A Decade of Drug-Eluting Technology in Peripheral Arterial Disease: Blurred by Dissembling Evidence. PMID- 27671155 TI - Radiologic Placement of Uncovered Stents for the Treatment of Malignant Colonic Obstruction Proximal to the Descending Colon. AB - PURPOSE: To evaluate the safety, feasibility, and patency rates of radiologic placement of uncovered stents for the treatment of malignant colonic obstruction proximal to the descending colon. MATERIALS AND METHODS: This was a retrospective, single-center study. From May 2003 to March 2015, 53 image-guided placements of uncovered stents (44 initial placements, 9 secondary placements) were attempted in 44 patients (male:female = 23:21; mean age, 71.8 years). The technical and clinical success, complication rates, and patency rates of the stents were also evaluated. Technical success was defined as the successful deployment of the stent under fluoroscopic guidance alone and clinical success was defined as the relief of obstructive symptoms or signs within 48 h of stent deployment. RESULTS: In total, 12 (27.3 %) patients underwent preoperative decompression, while 32 (72.7 %) underwent decompression with palliative intent. The technical success rate was 93.2 % (41/44) for initial placement and 88.9 % (8/9) for secondary placement. Secondary stent placement in the palliative group was required in nine patients after successful initial stent placement due to stent obstruction from tumor ingrowth (n = 7) and stent migration (n = 2). The symptoms of obstruction were relieved in all successful cases (100 %). In the palliative group, the patency rates were 94.4 % at 1 month, 84.0 % at 3 months, 64.8 % at 6 months, and 48.6 % at 12 months. CONCLUSIONS: The radiologic placement of uncovered stents for the treatment of malignant obstruction proximal to the descending colon is feasible and safe, and provides acceptable clinical results. PMID- 27671156 TI - Our Identity Crisis and a Solution: The One Mind. PMID- 27671157 TI - Differential tinnitus-related neuroplastic alterations of cortical thickness and surface area. AB - Structural neuroimaging techniques have been used to identify cortical and subcortical regions constituting the neuroarchitecture of tinnitus. One recent investigation used voxel-based morphometry (VBM) to analyze a sample of tinnitus patients (TI, n = 257) (Schecklmann et al., 2013). A negative relationship between individual distress and cortical volume (CV) in bilateral auditory regions was observed. However, CV has meanwhile been identified as a neuroanatomical measurement that confounds genetically distinct neuroanatomical traits, namely cortical thickness (CT) and cortical surface area (CSA). We performed a re-analysis of the identical sample using the automated FreeSurfer surface-based morphometry (SBM) approach (Fischl, 2012). First, we replicated the negative correlation between tinnitus distress and bilateral supratemporal gray matter volume. Second, we observed a negative correlation for CSA in the left periauditory cortex and anterior insula. Furthermore, we noted a positive correlation between tinnitus duration and CT in the left periauditory cortex as well as a negative correlation in the subcallosal anterior cingulate, a region collated to the serotonergic circuit and germane to inhibitory functions. In short, the results elucidate differential neuroanatomical alterations of CSA and CT for the two independent tinnitus-related psychological traits distress and duration. Beyond this, the study provides further evidence for the distinction and specific susceptibility of CSA and CT within the context of neuroplasticity of the human brain. PMID- 27671158 TI - Biomechanical factors behind toe clearance during the swing phase in hemiparetic patients. AB - BACKGROUND: The toe clearance of a paretic limb in the swing phase of gait is related to tripping, which is considered a major cause of falls. The biomechanical factors for obtaining toe clearance are more complicated in hemiparetic gait than that in normal gait because of the compensatory movements during swing phase. Understanding the biomechanical factors should help in targeting the point for rehabilitative interventions. OBJECTIVE: To clarify the biomechanical factors behind toe clearance during swing phase in hemiparetic gait. METHODS: Fifty patients with hemiparesis after a stroke participated in this study. Three-dimensional motion analysis was used for the kinematic analysis of the hemiparetic gait. The correlation coefficients between limb shortening and angle changes and between limb shortening and hip elevation and foot lateral shift were calculated. Limb shortening was defined as the shortening of the hip toe distance. The significant factors that determine toe clearance were examined by multiple regression analysis. Independent variables were limb shortening, hip elevation, and foot lateral shift. RESULTS: Limb shortening was negatively correlated with hip elevation (r = -0.75) and foot lateral shift (r = -0.41). Multiple regression analysis showed a significant contribution of limb shortening and hip elevation to toe clearance. The coefficient of determination was 0.95. CONCLUSIONS: Toe clearance was mainly determined by limb shortening and hip elevation, which were found to be in a trade-off relationship. These results warrant further investigation into the use of three-dimensional motion analysis in the rehabilitation clinic to facilitate targeted rehabilitative training to restore gait ability. PMID- 27671159 TI - Retrospective forecasting of the 2010-2014 Melbourne influenza seasons using multiple surveillance systems. AB - Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, since these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, and we have previously tailored these methods for metropolitan Melbourne (Australia) and Google Flu Trends data. Here we extend these methods to clinical observation and laboratory confirmation data for Melbourne, on the grounds that these data sources provide more accurate characterizations of influenza activity. We show that from each of these data sources we can accurately predict the timing of the epidemic peak 4-6 weeks in advance. We also show that making simultaneous use of multiple surveillance systems to improve forecast skill remains a fundamental challenge. Disparate systems provide complementary characterizations of disease activity, which may or may not be comparable, and it is unclear how a 'ground truth' for evaluating forecasts against these multiple characterizations might be defined. These findings are a significant step towards making optimal use of routine surveillance data for outbreak forecasting. PMID- 27671160 TI - Salinity-mediated transcriptional and post-translational regulation of the Arabidopsis aquaporin PIP2;7. AB - KEY MESSAGE: Salt stress triggers a simultaneous transcriptional repression and aquaporin internalization to modify root cell water conductivity. Plasma membrane intrinsic proteins (PIPs) are involved in the adjustment of plant water balance in response to changing environmental conditions. In this study, Arabidopsis wild type (Col-0) and transgenic lines overexpressing PIP2;7 were used to investigate and compare their response to salt stress. Hydraulic conductivity measurements using a high-pressure flowmeter (HPFM) revealed that overexpression of PIP2;7 induced a sixfold increase in root hydraulic conductivity of four week-old Arabidopsis thaliana plants compared to WT. Exposure to a high salt stress (150 mM NaCl) triggered a rapid repression of overall aquaporin activity in both genotypes. Response to salt stress was also investigated in 8 day-old seedlings. Exposure to salt led to a repression of PIP2;7 promoter activity and a significant decrease in PIP2;7 mRNA abundance within 2 h. Concomitantly, a rapid internalization of fluorescently-tagged PIP2;7 proteins was observed but removal from the cell membrane was not accompanied by further degradation of the protein within 4 h of exposure to salinity stress. These data suggest that PIP transcriptional repression and channel internalization act in concert during salt stress conditions to modulate aquaporin activity, thereby significantly altering the plant hydraulic parameters in the short term. PMID- 27671161 TI - Assessment of Isoprostanes in Human Plasma: Technical Considerations and the Use of Mass Spectrometry. AB - Oxygenated lipid mediators released from non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) are known to have functional roles in humans. Notably, among these lipid mediators, isoprostanes molecules are robust biomarkers of oxidative stress but those from n-3 PUFA are also bioactive molecules. In order to identify and assess the isoprostanes, the use of mass spectrometry (MS) for analysis is preferable and has been used for over two decades. Gas chromatography (GC) is commonly coupled to the MS to separate the derivatized isoprostanes of interest in biological samples. In order to increase the accuracy of the analytical performance, GC-MS/MS was also applied. Lately, MS or MS/MS has been coupled with high-performance liquid chromatography to assess multiple isoprostane molecules in a single biological sample without derivatization process. However, there are limitations for the use of LC-MS/MS in the measurement of plasma isoprostanes, which will be discussed in this review. PMID- 27671162 TI - Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. AB - BACKGROUND: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. METHODS: Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. RESULTS: In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+, CD11c+, and FcepsilonRI+) than adults with AD. Similar to adults, strong activation of the TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-gamma and CXCL10) were present. Children showed significantly higher induction of TH17 related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). CONCLUSION: The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation. PMID- 27671165 TI - Winners of the 2015 JA Medals for excellence. PMID- 27671163 TI - Advances in breeding for high grain Zinc in Rice. AB - Zinc (Zn) is one of the most essential micronutrients required for the growth and development of human beings. More than one billion people, particularly children and pregnant women suffer from Zn deficiency related health problems in Asia. Rice is the major staple food for Asians, but the presently grown popular high yielding rice varieties are poor supplier of Zn in their polished form. Breeding rice varieties with high grain Zn has been suggested to be a sustainable, targeted, food-based and cost effective approach in alleviating Zn deficiency. The physiological, genetic and molecular mechanisms of Zn homeostasis have been well studied, but these mechanisms need to be characterized from a biofortification perspective and should be well integrated with the breeding processes. There is a significant variation for grain Zn in rice germplasm and efforts are being directed at exploiting this variation through breeding to develop high Zn rice varieties. Several QTLs and gene specific markers have been identified for grain Zn and there is a great potential to use them in Marker Assisted Breeding. A thorough characterization of genotype and environmental interactions is essential to identify key environmental factors influencing grain Zn. Agronomic biofortification has shown inconsistent results, but a combination of genetic and agronomic biofortification strategies may be more effective. Significant progress has been made in developing high Zn rice lines for release in target countries. A holistic breeding approach involving high Zn trait development, high Zn product development, product testing and release, including bioefficacy and bioavailability studies is essential for successful Zn biofortification. PMID- 27671164 TI - Analysis of Allelic Imbalance in Rice Hybrids Under Water Stress and Association of Asymmetrically Expressed Genes with Drought-Response QTLs. AB - BACKGROUND: Information on the effect of stress on the allele-specific expression (ASE) profile of rice hybrids is limited. More so, the association of allelically imbalanced genes to important traits is yet to be understood. Here we assessed allelic imbalance (AI) in the heterozygote state of rice under non- and water stress treatments and determined association of asymmetrically expressed genes with grain yield (GY) under drought stress by in-silico co-localization analysis and selective genotyping. The genotypes IR64, Apo and their F1 hybrid (IR64 * Apo) were grown under normal and water-limiting conditions. We sequenced the total RNA transcripts for all genotypes then reconstructed the two chromosomes in the heterozygote. RESULTS: We are able to estimate the transcript abundance of and the differential expression (DE) between the two parent-specific alleles in the rice hybrids. The magnitude and direction of AI are classified into two categories: (1) symmetrical or biallelic and (2) asymmetrical. The latter can be further classified as either IR64- or Apo-favoring gene. Analysis showed that in the hybrids grown under non-stress conditions, 179 and 183 favor Apo- and IR64 specific alleles, respectively. Hence, the number of IR64- and Apo-favoring genes is relatively equal. Under water-stress conditions, 179 and 255 favor Apo- and IR64-specific alleles, respectively, indicating that the number of allelically imbalanced genes is skewed towards IR64. This is nearly 40-60 % preference for Apo and IR64 alleles, respectively, to the hybrid transcriptome. We also observed genes which exhibit allele preference switching when exposed to water-stress conditions. Results of in-silico co-localization procedure and selective genotyping of Apo/IR64 F3:5 progenies revealed significant association of several asymmetrically expressed genes with GY under drought stress conditions. CONCLUSION: Our data suggest that water stress skews AI on a genome-wide scale towards the IR64 allele, the cross-specific maternal allele. Several asymmetrically expressed genes are strongly associated with GY under drought stress which may shed hints that genes associated with important traits are allelically imbalanced. Our approach of integrating hybrid expression analysis and QTL mapping analysis may be an efficient strategy for shortlisting candidate genes for gene discovery. PMID- 27671166 TI - Adherence to recommended exercise guidelines in patients with heart failure. AB - Exercise training has been shown to be beneficial in patients with heart failure, and its effectiveness is connected to adherence to the exercise program. Nonetheless, adherence to exercise in these patients remains a concern. Heart failure patients can be considered adherent to an exercise program if they meet 80 % of the recommended dose. We summarize exercise recommendations for patients with heart failure, identify exercise prescription methodologies used in studies that have reported exercise adherence, identify strategies and tools used to improve adherence and examine whether these strategies were developed using a theoretical platform with the primary aim to change behavior and improve adherence to exercise. Factors which may also impact adherence such as exercise setting, intensity and length of participation, gender, race, New York Heart Association functional class and heart failure with preserved and reduced ejection fraction were also investigated. Finally, recommendations for future studies for improving adherence to exercise in patients with heart failure are provided. PMID- 27671168 TI - Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage. AB - PURPOSE: Reports on long-term variations in pituitary function after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) diverge. The aim of the current study was to evaluate the prevalence and changes in pituitary function during the first year after moderate and severe TBI and SAH and to explore the relation between pituitary function and injury variables. METHODS: Adults with moderate and severe TBI or SAH were evaluated at 10 days, 3, 6 and 12 months post injury/illness. Demographic, clinical, radiological, laboratory, including hormonal data were collected. RESULTS: A total of 91 adults, 56 (15 women/41 men) with TBI and 35 (27 women/8 men) with SAH were included. Perturbations in pituitary function were frequent early after the event but declined during the first year of follow-up. The most frequent deficiency was hypogonadotrope hypogonadism which was seen in approximately 25 % of the patients. Most of the variations were transient and without clinical significance. At 12 months, two patients were on replacement with hydrocortisone, four men on testosterone and one man on replacement with growth hormone. No relations were seen between hormonal levels and injury variables. CONCLUSIONS: Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy. Our study could not identify a marker of increased risk of pituitary dysfunction that could guide routine screening. However, data demonstrate the need for systematic follow-up of pituitary function after moderate or severe TBI or SAH. PMID- 27671169 TI - Evaluating targeted interventions via meta-population models with multi-level mixing. AB - Among the several means by which heterogeneity can be modeled, Levins' (1969) meta-population approach preserves the most analytical tractability, a virtue to the extent that generality is desirable. When model populations are stratified, contacts among their respective sub-populations must be described. Using a simple meta-population model, Feng et al. (2015) showed that mixing among sub populations, as well as heterogeneity in characteristics affecting sub-population reproduction numbers, must be considered when evaluating public health interventions to prevent or control infectious disease outbreaks. They employed the convex combination of preferential within- and proportional among-group contacts first described by Nold (1980) and subsequently generalized by Jacquez et al. (1988). As the utility of meta-population modeling depends on more realistic mixing functions, the authors added preferential contacts between parents and children and among co-workers (Glasser et al., 2012). Here they further generalize this function by including preferential contacts between grandparents and grandchildren, but omit workplace contacts. They also describe a general multi-level mixing scheme, provide three two-level examples, and apply two of them. In their first application, the authors describe age- and gender specific patterns in face-to-face conversations (Mossong et al., 2008), proxies for contacts by which respiratory pathogens might be transmitted, that are consistent with everyday experience. This suggests that meta-population models with inter-generational mixing could be employed to evaluate prolonged school closures, a proposed pandemic mitigation measure that could expose grandparents, and other elderly surrogate caregivers for working parents, to infectious children. In their second application, the authors use a meta-population SEIR model stratified by 7 age groups and 50 states plus the District of Columbia, to compare actual with optimal vaccination during the 2009-2010 influenza pandemic in the United States. They also show that vaccination efforts could have been adjusted month-to-month during the fall of 2009 to ensure maximum impact. Such applications inspire confidence in the reliability of meta-population modeling in support of public health policymaking. PMID- 27671170 TI - Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells. AB - Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- gamma against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies. PMID- 27671167 TI - Targeted Next Generation Sequencing Identifies Markers of Response to PD-1 Blockade. AB - Therapeutic antibodies blocking programmed death-1 and its ligand (PD-1/PD-L1) induce durable responses in a substantial fraction of melanoma patients. We sought to determine whether the number and/or type of mutations identified using a next-generation sequencing (NGS) panel available in the clinic was correlated with response to anti-PD-1 in melanoma. Using archival melanoma samples from anti PD-1/PD-L1-treated patients, we performed hybrid capture-based NGS on 236-315 genes and T-cell receptor (TCR) sequencing on initial and validation cohorts from two centers. Patients who responded to anti-PD-1/PD-L1 had higher mutational loads in an initial cohort (median, 45.6 vs. 3.9 mutations/MB; P = 0.003) and a validation cohort (37.1 vs. 12.8 mutations/MB; P = 0.002) compared with nonresponders. Response rate, progression-free survival, and overall survival were superior in the high, compared with intermediate and low, mutation load groups. Melanomas with NF1 mutations harbored high mutational loads (median, 62.7 mutations/MB) and high response rates (74%), whereas BRAF/NRAS/NF1 wild-type melanomas had a lower mutational load. In these archival samples, TCR clonality did not predict response. Mutation numbers in the 315 genes in the NGS platform strongly correlated with those detected by whole-exome sequencing in The Cancer Genome Atlas samples, but was not associated with survival. In conclusion, mutational load, as determined by an NGS platform available in the clinic, effectively stratified patients by likelihood of response. This approach may provide a clinically feasible predictor of response to anti-PD-1/PD-L1. Cancer Immunol Res; 4(11); 959-67. (c)2016 AACR. PMID- 27671172 TI - Community-Informed Health Promotion to Improve Health Behaviors in Honduras. AB - BACKGROUND: Honduras is the second poorest country in Central America. The already high burden of disease is disproportionately worse among individuals with less education and limited access to health care. Community engagement is needed to bridge the gap in health care resources with the need for health promotion and education. Culturally relevant health promotion activities can foster transcultural partnerships. PURPOSE: The purpose of this study was to partner nursing students with village leaders to assess a community's health needs and implement health promotion activities in Honduras. DESIGN: Participatory action research was used in the study. METHOD: U.S. nursing students ( n = 4) partnered with a nonprofit organization and community partners in Villa Soleada to interview mothers in Villa Soleada, a Honduran village of 44 families, and implement health promotion activities targeted to the health priorities of their families. RESULTS: Structured interviews with 24 mothers identified gastrointestinal issues, health care access and quality, and malaria as the top three priorities. Ninety-two percent of respondents were interested in nurse-led health promotion. Activities engaged new community partners. DISCUSSION: This partnership and learning model was well received and sustainable. The U.S. nurses involved in the partnership gained exposure to Honduran health issues and led locally tailored health promotions in Villa Soleada. The community's response to health promotion were positive and future activities were planned. IMPLICATIONS: Nursing student's immersion experiences to support population-based health activities in low-resource settings are a replicable model that can help build healthier communities with a sustainable local infrastructure. Transcultural nursing experiences enhance students' perspectives, increase personal and professional development, strengthen nursing students' critical thinking skills, and for some students, confirm their desire to practice in an international arena. PMID- 27671173 TI - Telomeres and Pace of Aging in the Developing World. PMID- 27671174 TI - Predictive Model for Blood Product Use in Coronary Artery Bypass Grafting. AB - OBJECTIVE: To build a clinical predictive model to determine the need for transfusing blood and its products in coronary artery bypass grafting (CABG) procedures in South East Asian population. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Section of Cardiothoracic Surgery, Aga Khan University Hospital, Karachi, from January 2006 to October 2014. METHODOLOGY: Information on pre-, intra- and postoperative variables were collected for all adult patients who underwent on-pump CABG. The patients grouped into those who received blood and its components, and those who did not. Aunivariate as well as multivariate logistic model was built to determine the predictors of transfusion. RESULTS: A total of 3,550 patients underwent CABG and males were dominant in both groups (75 vs. 93%). The transfusion rate was 56.4% (n=2001). Age (adjusted OR 1.03, p < 0.001), obesity (1.50, p=0.001), tobacco use (1.29, p=0.001), and male gender (4.51, p < 0.001) found to be a stronger predictor. Among preoperative comorbidities, diabetes (1.20, p=0.016), myocardial infarction (1.22, p=0.009), preoperative creatinine (1.12, p=0.033), and left main vessel disease of > 50% (1.49, p < 0.001) were independently associated with the outcome. Compared to elective cases, transfusion rates were high in urgent and emergent cases (OR: 1.93 and 3.36 respectively, p < 0.001 for both). CONCLUSION: Age, male gender, obesity, tobacco use, diabetes, myocardial infarction, high creatinine, urgent and emergent cases were independent predictors of transfusion in CABG procedure. This model can be utilized for preoperative risk stratification of patients and their management to improve the outcomes. PMID- 27671175 TI - Skeletonization of Left Internal Mammary Artery in Coronary Artery Bypass Grafting. AB - OBJECTIVE: To compare mean per-operative flow capacity between skeletonized and pedicled left internal mammary artery (LIMA) in patients undergoing coronary artery bypass grafting (CABG) surgery. STUDY DESIGN: Randomized control trial. PLACE AND DURATION OF STUDY: Department of Cardiac Surgery, Armed Forces Institute of Cardiology and National Institute of Heart Diseases (AFIC-NIHD), Rawalpindi, Pakistan from February to August, 2013. METHODOLOGY: Patients undergoing CABG for coronary artery disease, under 80 years, excluded by the exclusion criteria; and fulfilling the inclusion criteria were randomly assigned to two groups of 70 each. One group underwent skeletonized and the other underwent pedicled technique of LIMAharvesting. Free flow was checked just before anastamosis of each LIMAto the LAD, manually in blood flow in ml per minute during cardiopulmonary bypass by allowing it to bleed into a 100 ml container over 20 seconds. Aspecialized proforma was used to record the age, gender, weight, disease, type of IMA used, and free flow of the IMA. Data was analyzed using SPSS 18. RESULTS: The mean age of the patients was 57.16 years in 40 patients, ranging from 36 to 75 years. Disease pattern analysis showed 5%, 10.7% and 84.3% single, double and triple vessel coronary artery disease, respectively. There was significantly higher free flow in the skeletonized group than the pedicled group (p=0.04). CONCLUSION: Skeletonized IMAhad superior flow to pedicled IMAin addition to its traditional proven advantages, which justifies its further use as a conduit for myocardial revascularization. PMID- 27671176 TI - Peripartum Cardiomyopathy in a Pakistani Cohort. AB - OBJECTIVE: To describe the demographics, risk factors, and clinical presentation in Pakistani patients with peripartum cardiomyopathy. STUDY DESIGN: A descriptive observational study. PLACE AND DURATION OF STUDY: Rawalpindi Institute of Cardiology, Rawalpindi, from June 2014 to June 2015. METHODOLOGY: Seventy patients meeting criteria of peripartum cardiomyopathy were included in the study. Adetailed history, physical examination and investigations were done. Epidemiologic data, risk factors, New York Heart Association (NYHA) class and echocardiographic findings were recorded. Statistical analyses were done using SPSS version 19. RESULTS: The mean age was 28.66 +/-4.57 years. Mean parity and weight was 3.04 +/-1.7 and 60.97 +/-12.40 Kg, respectively. Fifty-five (78.6%) cases were diagnosed in the postpartum period. Thirty-three (50.8%) and 31 patients (44.7%) presented in NYHA- III and IV classes, respectively. Pregnancy induced hypertension was seen in 16 (22.9%) cases, diabetes in 6 (8.6%), and twin pregnancy in 2 (2.9%) cases. The mean hemoglobin and brain natriuretic peptide (BNP) was 11.26 +/-1.61 gm/dl and 1583.70 +/-1237.65 pg/ml, respectively. Echocardiography showed mean ejection fraction of 21.74 +/-7.45%. Left ventricle systolic and diastolic diameters were 53.71 +/-9.74 mm and 63.37 +/-8.48 mm, respectively. CONCLUSION: Peripartum cardiomyopathy was seen in younger women with higher parity and pregnancy induced hypertension, often manifesting in the postpartum period with NHYAclass III and IV status. PMID- 27671171 TI - The neural retina in retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP. PMID- 27671177 TI - Caries with Dental Fluorosis and Oral Health Behaviour Among 12-Year School Children in Moderate-Fluoride Drinking Water Community in Quetta, Pakistan. AB - OBJECTIVE: To determine the prevalence of dental caries and its relationship with dental fluorosis, oral health behaviour and dietary behaviour among 12-year school children in moderate-fluoride drinking water community in Quetta, Pakistan. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Government and private schools of Quetta, from November 2012 to February 2013. METHODOLOGY: Atotal of 349 children aged 12-year from 14 randomly selected schools were included. The data collection was done on questionnaire designed for children. Dental caries status was examined by using WHO criteria. RESULTS: Dental caries was found in 81 children (23.2%) with mean DMFT0.61. Boys had 1.6 times more chance to have dental caries than girls. Dental fluorosis was found in 63.6% of children with majority of moderate degree (50.5%). Dental fluorosis status was found significantly associated with dental caries status in children. The children who had mild, moderate and severe fluorosis, had 4 times more chances to develop caries than those who did not have fluorosis. There was no significant association between children's caries status and use of paste, brushing habit, miswak, and visit to the dentist. The use of pastries and juices had a direct relation with the children's dental caries status. CONCLUSION: Dental caries in children of Quetta is not so much frequent as compared to the fluoride deficient countries. However, the high prevalence of moderate dental fluorosis and consumption of pastries and juices resulted in dental caries. PMID- 27671178 TI - An In-VitroEvaluation of Microleakage at the Cervical Margin Between two Different Class II Restorative Techniques Using Dye Penetration Method. AB - OBJECTIVE: To evaluate the coronal microleakage of packable composite using conventional incremental and posterior bulk fill flowable composite using Smart Dentine Replacement Single Step technique in the cervical margins of class II cavities in dentine using the dye penetration method. STUDY DESIGN: In vitroInterventional study. PLACE AND DURATION OF STUDY: Department of Operative Dentistry, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences (DIKIOHS), Karachi, from November 2012 to April 2013. METHODOLOGY: One hundred and twenty extracted teeth (molars and premolars) were collected and randomly divided into two experimental groups (n=60 each) and were stored in normal saline until used. Fractured samples were excluded. Standardized class II proximal box only cavities were prepared and restored with conventional methacrylate based composite using incremental technique (Group A, n=40) and low stress methacrylate resin based composite SDR using single step technique (Group B, n=40). Samples were sectioned horizontally below the cervical margins and specimen disks were prepared. The specimens were thermocycled and sealed with acid resistant varnish leaving a 1-mm interface around cervical margin and immersed in 2% methylene blue buffered solution for 24 hours. Leakage was scored 0 - 4 and measured in mm. It washed and sectioned to evaluate under stereomicroscope. RESULTS: Mean penetration was 2.4280 +/-0.79 mm for Group Aand 1.015 +/-0.45 mm for Group B (p < 0.001). Maximum dye penetration score for group Awas 4 and group B was 3. CONCLUSION: SDR technique in combination with total etch technique at the cervical margin of class II restorations improved the marginal seal, when were placed in dentine and thermocycled. PMID- 27671179 TI - Dentoalveolar Heights in Vertical and Sagittal Facial Patterns. AB - OBJECTIVE: To determine and compare the mean dentoalveolar heights (mm) in different vertical and sagittal facial patterns. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Orthodontics Clinic, The Aga Khan University Hospital, Karachi, from September to November 2013. METHODOLOGY: Subjects, aged 15 - 20 years, having fully erupted first permanent molars and central incisors were included in the study from orthodontic records. The pretreatment cephalographs of subjects were traced manually over an illuminator. The various parameters like angles and dentoalveolar heights were measured and recorded on data collection form. Mean value +/- SD for the variables were generated. ANOVAwas used to compare the means of dentoalveolar heights among the vertical and sagittal facial patterns. Post Hoc Bonferroni test was applied to show difference among the three vertical and three sagittal facial patterns. P-value equal to or less than 0.05 was taken as statistically significant. RESULTS: The mean age of subjects was 15.8 +/-3.2 years in vertical group and 16.3 +/-2.9 years in sagittal group. There was statistically significant difference (p=0.008) for the upper anterior dentoalveolar height (UADH) among vertical groups, with statistically significant difference for UADH between hyperdivergent and normodivergent (p=0.04) and hyperdivergent and hypodivergent (p=0.01) facial patterns. CONCLUSION: The UADH were significantly greater in the hyperdivergent group as compared to both the normodivergent and hypodivergent groups. The sagittal groups showed no statistically significant difference for dentoalveolar heights. PMID- 27671180 TI - Optic Nerve Sheath Diameter on Sonography in Idiopathic Intracranial Hypertension Versus Normal. AB - OBJECTIVE: To compare the mean optic nerve sheath diameter (ONSD) in patients with idiopathic intracranial hypertension (IIH) versus normal healthy individuals using B-scan ultrasonography as diagnostic tool. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Radiology and Imaging, Rawalpindi, Pakistan, from June to December 2015. METHODOLOGY: Participants aged 30 - 50 years were divided into two groups. Group A(GP) comprised of patients who were diagnosed cases of idiopathic intracranial hypertension while normal healthy adults who volunteered to participate in the study were included in Group B (GC). Ocular B mode ultrasound scan was performed on all the participants and each eye was considered separately. The optic nerve head was visualized as a linear hypoechoic structure, and ONSD was measured 3 mm behind the retina. Atotal of three readings were taken by the same radiologist and the average of three was recorded. Mean values of both groups were compared by t-test with significance at p < 0.05. RESULTS: Fifty-two eyes of 26 patients (26 eyes in each group) were included in the study. Twenty-four out of 26 in Group A(GP) and 23 out of 26 in Group B (GC) were females. Mean age of the patients was 33.92 +/-4.89 years in group A(GP) while it was 34.69 +/-4.79 years in group B (GC). Mean ONSD was 6.61 +/-0.39 mm in group A(GP) and 4.33 +/-0.38 mm in group B(GC) which was significantly different (p < 0.001). CONCLUSION: Ultrasound can provide a reliable, non-invasive tool to measure optic nerve sheath diameter in monitoring the patients with benign intracranial hypertension (BIH). PMID- 27671181 TI - Effects of Glucose Administration on Development of Sclera in Chick Embryos. AB - OBJECTIVE: To determine the effect of glucose administration on the development of sclera in the chick embryo Gallus domesticus. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Anatomy Department, CPSPRegional Centre, Islamabad, from January 2013 to January 2014. METHODOLOGY: The study was carried out in two main groups, control Aand experimental B, which were subdivided into three subgroups comprising 30 eggs each. The group Awas injected with normal saline (0.3 ml) in the egg albumen. The group B was injected with 0.3 ml of 5% w/v solution of glucose equivalent to 15 mg of glucose. Subgroups A1 and B1 were opened on day 10 of incubation. Subgroups A2 and B2 were sacrificed on day 12 of incubation. Eggs from subgroups A3 and B3 were opened on day 15 of incubation. Experimental subgroups were compared with matched control subgroups and quantitative data was analysed statistically. RESULTS: Administration of glucose resulted in changes in thickness of sclera. The mean thickness (um) of sclera at day 10 of incubation was 43.54 +/-2.45 in control subgroup and 43.03 +/-5.86 in the experimental subgroup (p=0.673). The mean thickness (um) of sclera at day 15 of incubation 77.48 +/-8.32 in control subgroup and 73.99 +/-8.62 in experimental subgroup (p=0.145). The mean number of chondrocytes/unit area of hyaline cartilage of sclera in day 10 was 17.40 +/-1.44 control subgroup and 14.57 +/ 1.87 in the experimental subgroup (p < 0.001). The mean number of chondrocytes/unit area of hyaline cartilage of sclera on day 15 was 10.02 +/-0.86 in the control subgroup and 9.54 +/-0.59 in the experimental subgroup (p=0.025). There was disrupted ossicular formation indicating adverse effects on the development of bony sclera as well. CONCLUSION: Administration of glucose caused alteration in the histology of sclera in developing chick embryos. PMID- 27671182 TI - Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) for Diagnosis of Mediastinal and Hilar Masses. AB - OBJECTIVE: To determine the sensitivity, specificity, negative and positive predictive values, and diagnostic accuracy of Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA). STUDY DESIGN: Across-sectional validation study. PLACE AND DURATION OF STUDY: Department of Histopathology, Army Medical College, in collaboration with Department of Pulmonology, Military Hospital Rawalpindi, from March 2014 to March 2015. METHODOLOGY: Cases of EBUS TBNAcomprised of both TBNAs and cell block/biopsy of the same patients. Diagnosis was made on the TBNAslides and cell block/biopsy material. Taking biopsy/cell block as the gold standard, the data was analysed to calculate the sensitivity, specificity, negative and positive predictive values, and diagnostic accuracy of EBUSTBNA. RESULTS: The sensitivity of EBUS-TBNAwas found to be 96.5%; whereas, specificity and positive predictive values were 100%. The negative predictive value was calculated at 50%. Diagnostic accuracy of the procedure was found to be 96.67%. CONCLUSION: EBUS-TBNA is a sensitive and a specific test and is accurate in diagnosing mediastinal and hilar pathologies. PMID- 27671184 TI - Association of Smokeless Tobacco with Oral Cancer - Evidence From the South Asian Studies: A Systematic Review. AB - Smokeless tobacco (SLT) is associated with many heath hazards including oral cancer. Its use is more common in South Asian countries. The current paper aims to systematically review the South Asian studies to assess the association of SLT and oral cancer. Detailed automated literature searches of PubMed, Medline, EMBASE and ISI Web of Science from January 1980 to July 2015 were conducted using the key words "oral cancer", "oral precancer", "oral premalignant lesions", "oral squamous cell carcinoma", "smokeless tobacco", "betel quid", "areca nut", "Gutkha" in various combinations. Letters to the editor, review articles, and case-reports were excluded. Atotal of 21 studies were included. Three studies were of cohort design while the remaining were of case-control design. Nine studies reported betel quid as a risk factor for oral cancer, while fifteen studies reported data on other types of chewing tobacco. The odds ratio (OR) for betel quid and risk of oral cancer varied from 3.1 to 15.7 (11.0-22.1); and for chewable tobacco and risk of oral cancer varied from 1.2 (1.0-1.4) to 12.9 (7.5 22.3). Astrong association between different types of SLTand oral cancer was observed. Well-structured programmes should be employed in South Asian region, both in terms of educating the general public about the health hazards of SLTas well as providing cessation assistance. PMID- 27671183 TI - Efficacy of Probiotics Versus Placebo in the Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double-Blind Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis (NEC) in preterm very low birth weight (VLBW) infants. STUDY DESIGN: Arandomized double blind controlled trial. PLACE AND DURATION OF STUDY: The Paediatrics Department of Sylhet M.A.G. Osmani Medical College Hospital, Sylhet Bangladesh, from July 2012 to June 2015. METHODOLOGY: Preterm (28 - 33 weeks gestation) VLBW (birth weight 1000 - 1499 g) neonates were enrolled. The study group was fed with probiotics once daily with breast milk from first feeding, and the control group with only breast milk without the addition of probiotics. Both the groups received other standard care. The primary outcome was the development of NEC (stage II and III), categorized by modified Bell's classification. RESULTS: In 108 neonates, development of NEC was significantly lower in the study group than that of control group [1 (1.9%) vs. 6 (11.5%); p=0.044]. Age of achievement of full oral feeding was significantly earlier in the study group than that in the control group (14.88 +/-3.15 and 18.80 +/-4.32 days; p < 0.001). Duration of hospital stay was significantly short in the study group compared to the control group (15.82 +/-2.94 days vs. 19.57 +/ 4.26 days; p < 0.001). CONCLUSION: Probiotic supplementation reduces the frequency of necrotising enterocolitis in preterm neonates with very low birth weight. It is also associated with faster achievement of full oral feeding and short duration of hospital stay. PMID- 27671185 TI - Parotid Cystic Lesion in Amelanotic Malignant Melanoma. AB - A 60-year Brazilian woman, presented with an enlarged lymph node in the neck for one year, and a superficial nonulcerated lesion was observed in the scalp. Fine needle aspiration and biopsy of the lymph node revealed amelanocytic metastasis, and immunohistochemistry study showed Melan-A/ Mart-1 antigen (clone A103 and S 100 protein). The entire suspected area of the scalp was further resected and an amelanotic melanoma without angiolymphatic invasion was diagnosed. Ultrasonography and PET-computed tomography showed hypermetabolic cystic area in the right parotid. Furthermore, aspiration biopsy and surgical samples from parotid cyst confirmed the malignant amelanotic melanoma. Cystic metastases are scarcely reported in parotid gland, and can pose diagnostic challenges. PMID- 27671186 TI - Congenital Limb Deficiency Associated with Intellectual Disability: Unusual Presentation in Two Subjects. AB - Congenital constriction ring (CCR) and symbrachydactyly are two distinct, rare, and heterogeneous limb deficiency conditions which affect the digits. Here, we report on two different individuals with an unusual presentation of limb deficiency accompanying intellectual disability (ID) and certain other malformations. In the first index female, CCR occurred with mild ID, squint eyes, obesity, and metatarsus adductus. The second index male was presented with symbrachydactyly, profound ID, and speech/hearing impairments. The association of limb deficiency conditions with these anomalies is very rare. Differential diagnosis and literature survey have been offered to establish the rarity of these entities. PMID- 27671188 TI - Allgrove Syndrome: Adrenal Insufficiency with Hypertensive Encephalopathy. AB - Allgrove syndrome or triple-Asyndrome is a rare familial multisystem autosomal recessive disorder. It is characterised by triad of alacrima, achalasia and adrenal insufficiency due to adrenocorticotropin hormone (ACTH) resistance. If it is associated with autonomic dysfunction, it is termed as 4-Asyndrome. This syndrome is caused by a mutation in the Achalasia - Addisonism - Alacrima (AAAS) gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. A5-year boy presented with history of fits and altered sensorium for one day. He also had increased pigmentation of body and persistent vomiting since six months of age. Laboratory investigations and imaging revealed alacrimia, achalasia and adrenal insufficiency due to ACTH resistance. He had episodes of hypertensive crises, for which he was thoroughly investigated and it was found to be due to autonomic instability. Based on clinical findings and investigations he was diagnosed as case of Allgrove syndrome or 4-Asyndrome with autonomic dysfunction. PMID- 27671187 TI - Chanarin-Dorfman Syndrome. AB - Chanarin-Dorfman syndrome is a rare, genetically determined autosomal recessive disorder, characterised by the presence of lipid droplets in the cytoplasm of multiple tissues of the body, particularly in the blood leukocytes and congenital non-bullous icthyosiform erythroderma. In this paper, we report one-year child who presented with skin lesions since birth and hepatomegaly. Liver biopsy showed steatohepatitis; and peripheral blood smear confirmed Jordan's anomaly, which is a permanent feature of Chanarin-Dorfman syndrome. PMID- 27671189 TI - Hand-Foot and Mouth Disease and Reactive Arthritis: An Unusual Paediatric Case. AB - Reactive arthritis is defined as arthritis that occurs during or after an extraarticular infection. It is mostly difficult to determine the causative agent that causes inflammation in the joints. Initially, salmonella, shigella, chlamydiaand yersinia were considered to be pathogenic agents. But recently, in addition to demonstrated viral and bacterial agents, there are also other cases of reactive arthritis after vaccinations with Rubella and Influenza. Herein a 3 year old boy is reported with reactive arthritis of left knee that developed shortly after hand-foot and mouth disease. This report represents the first detailed description of a paediatric case in literature with reactive arthritis following hand-foot and mouth disease. PMID- 27671190 TI - Flipped Class - Making that One Hour Effective in a Resource Constrained Setting. AB - Flipped-class teaching has a great potential to replace traditional lectures in medical education. This study was designed to explore attitude of undergraduate medical students from Pakistan towards flipped-class. Five flipped classes were conducted in third year MBBS by a single teacher for a class of 100 students. Quantitative data was collected through a survey questionnaire to assess students' response to the new method. Afocused group discussion was then conducted with students who disliked the method and preferred traditional lectures. Asequential mixed methods approach was used for analysis. Seventy-one students participated in the survey, 84.5% students liked this method of teaching. Students identified fruitful interaction, better retention, better conceptualisation, prior knowledge, active learning, individual student attention, and application of knowledge as strengths of the class. Noise, limited time, lack of self-confidence, and presence of uninterested students were identified as problems for engaging in the class. PMID- 27671191 TI - Clinical Utility of Immature Platelet Fraction - An Advanced Parameter in Laboratory Hematology. PMID- 27671192 TI - Tetanus Toxoid Vaccination of Pregnant Women in Pakistan. PMID- 27671193 TI - Intravascular Papillary Endothelial Hyperplasia of Palate. PMID- 27671194 TI - General Misconceptions Regarding Patient-Therapist Characteristics and Psychotherapy Outcome. PMID- 27671195 TI - Thickness of Achilles Tendon is BMI Dependant. PMID- 27671196 TI - Long-term disease-specific and cognitive quality of life after intensity modulated radiation therapy: a cross-sectional survey of nasopharyngeal carcinoma survivors. AB - BACKGROUND: There is a lack of data on quality of life in long-term survivors of nasopharyngeal carcinoma (NPC) who have been treated with intensity-modulated radiation therapy (IMRT). We characterized long-term disease-specific and cognitive QoL in NPC survivors after IMRT. METHODS: We conducted a cross sectional study of surviving patients diagnosed and treated for NPC at our center with curative-intent IMRT, with or without chemotherapy. Patients who were deceased, still undergoing treatment, with known recurrent disease, or treated with RT modality other than IMRT were excluded. QoL was measured by FACT-NP and FACT-Cog. RESULTS: Between May and November 2013, 44 patients completed cognitive (FACT-Cog), general (FACT-G), and NPC-specific (NPCS) QoL assessments. Patients were categorized into 4 cohorts based on duration since IMRT (<=2.5, >2.5-6, >6 10, and >10-16 years). There was no significant difference in age (p = 0.20) or stage ((I/II vs III/IV: p = 0.78) among the cohorts. The 4 cohorts differed overall for all QoL measures (ANOVA: p < 0.02 for each), due to improved scores >2.5-6 years post-IMRT compared with <=2.5 years post-IMRT (post hoc tests: p <= 0.04 for each). No differences were observed between >2.5-6 and >6-10 years post IMRT, but lower mean FACT-Cog and NPCS scores were observed for >10 years compared to >2.5-6 years post-IMRT (post hoc: p < 0.05 for each). CONCLUSIONS: All QoL measures were low during the initial recovery period (<=2.5 years) and were higher by 6 years post-IMRT. At >10 years post-IMRT, lower scores were observed in the domains of NPC-specific and cognitive QoL. Survivors of NPC, even if treated with IMRT, are at risk for detriment in domain-specific QoL measures at very long-term follow-up. PMID- 27671197 TI - Toward sensitive immuno-based detection of tau protein by surface plasmon resonance coupled to carbon nanostructures as signal amplifiers. AB - Interest on Tau protein is fast increasing in Alzheimer's disease (AD) diagnosis. There is the urgent need of highly sensitive and specific diagnostic platforms for its quantification, also in combination with the other AD hallmarks. Up to now, SPR has been poorly exploited for tau detection by immunosensing, due to sensitivity limits at nanomolar level, whereas the clinical requirement is in the picomolar range. Molecular architectures built in a layer-by-layer fashion, biomolecules and nanostructures (metallic or not) may amplify the SPR signal and improve the limit of detection to the desired sensitivity. Mostly gold nanostructures are widely employed to this aim, but great interest is also emerging in Multi Walled Carbon Nanotubes (MWCNTs). Here MWCNTs are modified and then decorated with the secondary antibody for tau protein. Eventually we took advantage from MWCNTs-antibody conjugate to obtain a sandwich-based bioassay with the capability to increase the SPR signal of about 102 folds compared to direct detection and conventional unconjugated sandwich. With respect to these results, we hope to give a strong impulse for further investigation on studying possible roles of carbon nanotubes in optical-based biosensing. PMID- 27671198 TI - BMP signaling modulates the probability of neurotransmitter release and readily releasable pools in Drosophila neuromuscular junction synapses. AB - The structure and function of synapses is modulated by the interaction of presynaptic and postsynaptic neurons via cell adhesion molecules or secreted signal molecules. Bone morphogenic protein (BMP) is a secreted molecule mediating retrograde signaling that is involved in the formation and maintenance of synaptic structure throughout many animal species. However, how BMP signaling modulates presynaptic neurotransmitter release is not yet clear. We studied the function of BMP signaling factors in neurotransmitter release in Drosophila neuromuscular synapses using loss-of-function mutants in genes for BMP modulators, Wit, Mad, and Dad. Larvae with mutations in wit and mad commonly showed a decreased synaptic bouton number in neuromuscular synapses. Larvae with dad mutations showed an increased bouton number. The amplitudes of miniature EJC (mEJC) were normal for these mutants. Wit and mad mutants showed decreased evoked EJC (eEJC) amplitude and increased paired pulse facilitation, implying impaired presynaptic neurotransmitter release. We found a reduction in readily releasable neurotransmitters pool sizes in wit and mad mutants. However, dad mutants showed a normal probability of neurotransmitter release and readily releasable pool sizes and normal eEJC amplitude even with clear abnormalities in synaptic structure. These results suggested that BMP signaling was critical for each step of presynaptic neurotransmission. The results also suggested that BMP signaling modulated both synaptic structure and function independently and specifically. PMID- 27671199 TI - Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle. AB - Muscle wasting is estimated to affect 40-60% of alcoholics, and is more common than cirrhosis among chronic alcohol abusers. The molecular and cellular mechanisms underlying alcohol-related musculoskeletal dysfunction are, however, poorly understood. Muscle-specific microRNAs (miRNAs) referred to as myoMirs are now known to play a key role in both myogenesis and muscle atrophy. Yet, no studies have investigated a role for myoMirs in alcohol-related skeletal muscle damage. We developed a zebrafish model of chronic ethanol exposure to better define the mechanisms mediating alcohol-induced muscle atrophy. Adult fish maintained at 0.5% ethanol for eight weeks demonstrated significantly reduced muscle fiber cross-sectional area (~12%, P < 0.05) compared to fish housed in normal water. Zebrafish miRNA microarray revealed marked changes in several miRNAs with ethanol treatment. Importantly, miR-140, a miRNA that shows 100% sequence homology with miR-140 from both mouse and human, is decreased 10-fold in ethanol treated fish. miR-140 targets several members of the Notch signaling pathway such as DNER, JAG1, and Hey1, and PCR data show that both Hey1 and Notch 1 are significantly up-related (3-fold) in muscle of ethanol treated fish. In addition, miR-146a, which targets the Notch antagonist Numb, is elevated in muscle from ethanol-treated fish. Upregulation of Notch signaling suppresses myogenesis and maintains muscle satellite cell quiescence. These data suggest that miRNAs targeting Notch are likely to play important roles in alcohol-related myopathy. Furthermore, zebrafish may serve as a useful model for better understanding the role of microRNAs in alcohol-related tissue damage. PMID- 27671200 TI - Enzymatic and thermodynamic profiles of a heterotetramer lactate dehydrogenase isozyme in swine. AB - Lactate dehydrogenase (LDH) is a glycolytic enzyme that catalyzes the final step of glycolysis and produces NAD+. In somatic cells, LDH forms homotetramers and heterotetramers that are encoded by two different genes: LDHA (skeletal muscle type, M) and LDHB (heart type, H). Analysis of LDH isozymes is important for understanding the physiological role of homotetramers and heterotetramers and for optimizing inhibition of their enzymatic activity as it may result in distinct effects. Previously, we reported that hydroxychloroquine (HCQ) inhibited LDH activity, but we did not examine isozyme specificity. In the present study, we isolated heterotetrameric LDH (H2M2) from swine brain, determined its kinetic and thermodynamic properties, and examined the effect of HCQ on its activity compared to homotetrameric LDH isozymes. We show that: (1) the Km values for H2M2-mediated catalysis of pyruvate or lactate were intermediate compared to those for the homotetrameric isozymes, M4 and H4 whereas the Vmax values were similar; (2) the Km and Vmax values for H2M2-mediated catalysis of NADH were not significantly different among LDH isozymes; (3) the values for activation energy and van't Hoff enthalpy changes for pyruvate reduction of H2M2 were intermediate compared to those for the homotetrameric isozymes; (4) the temperature for half residual activity of H2M2 was closer to that for M4 than for H4. We also show that HCQ had different affinities for various LDH isozymes. PMID- 27671201 TI - Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells. AB - Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626-740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626-740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells. PMID- 27671204 TI - Field emission of carbon quantum dots synthesized from a single organic solvent. AB - In this paper, a facile synthesis of carbon quantum dots (CQDs) and its field emission performance are reported. The CQDs are prepared from a single N, N dimethylformamide acting as carbon and nitrogen-doping sources simultaneously. The CQDs are investigated by photoluminescence, transmission electron microscopy and x-ray photoelectron spectroscopy. The CQDs have an average size of 3 nm and are doped with N atoms. CQD dispersion shows strong fluorescence under UV illumination. For the first time, the field emission behavior of CQDs coated on Si substrate is studied. As a candidate of cold cathode, the CQDs display good field emission performance. The CQD emitter reaches the current density of 1.1 mA cm(-2) at 7.0 V MUm(-1) and exhibits good long-term emission stability, suggesting promising application in field emission devices. PMID- 27671203 TI - The essence of life. AB - : Although biology has achieved great successes in recent years, we have not got a clear idea on "what is life?" Actually, as explained here, the main reason for this situation is that there are two completely distinct aspects for "life", which are usually talked about together. Indeed, in respect to these two aspects: Darwinian evolution and self-sustaining, we must split the concept of life correspondingly, for example, by defining "life form" and "living entity", separately. For life's implementation (related to the two aspects) in nature, three mechanisms are crucial: the replication of DNA/RNA-like polymers by residue pairing, the sequence-dependent folding of RNA/protein-like polymers engendering special functions, and the assembly of phospholipid-like amphiphiles forming vesicles. The notion "information" is significant for us to comprehend life phenomenon: the life form of a living entity can just be defined by its genetic information; Darwinian evolution is essentially an evolution of such information, transferred across generations. The in-depth analysis concerning the essence of life would improve our cognition in the whole field of biology, and may have a direct influence on its subfields like the origin of life, artificial life and astrobiology. REVIEWERS: This article was reviewed by Anthony Poole and Thomas Dandekar. PMID- 27671202 TI - Expansion of medical vocabularies using distributional semantics on Japanese patient blogs. AB - BACKGROUND: Research on medical vocabulary expansion from large corpora has primarily been conducted using text written in English or similar languages, due to a limited availability of large biomedical corpora in most languages. Medical vocabularies are, however, essential also for text mining from corpora written in other languages than English and belonging to a variety of medical genres. The aim of this study was therefore to evaluate medical vocabulary expansion using a corpus very different from those previously used, in terms of grammar and orthographics, as well as in terms of text genre. This was carried out by applying a method based on distributional semantics to the task of extracting medical vocabulary terms from a large corpus of Japanese patient blogs. METHODS: Distributional properties of terms were modelled with random indexing, followed by agglomerative hierarchical clustering of 3 *100 seed terms from existing vocabularies, belonging to three semantic categories: Medical Finding, Pharmaceutical Drug and Body Part. By automatically extracting unknown terms close to the centroids of the created clusters, candidates for new terms to include in the vocabulary were suggested. The method was evaluated for its ability to retrieve the remaining n terms in existing medical vocabularies. RESULTS: Removing case particles and using a context window size of 1+1 was a successful strategy for Medical Finding and Pharmaceutical Drug, while retaining case particles and using a window size of 8+8 was better for Body Part. For a 10n long candidate list, the use of different cluster sizes affected the result for Pharmaceutical Drug, while the effect was only marginal for the other two categories. For a list of top n candidates for Body Part, however, clusters with a size of up to two terms were slightly more useful than larger clusters. For Pharmaceutical Drug, the best settings resulted in a recall of 25 % for a candidate list of top n terms and a recall of 68 % for top 10n. For a candidate list of top 10n candidates, the second best results were obtained for Medical Finding: a recall of 58 %, compared to 46 % for Body Part. Only taking the top n candidates into account, however, resulted in a recall of 23 % for Body Part, compared to 16 % for Medical Finding. CONCLUSIONS: Different settings for corpus pre-processing, window sizes and cluster sizes were suitable for different semantic categories and for different lengths of candidate lists, showing the need to adapt parameters, not only to the language and text genre used, but also to the semantic category for which the vocabulary is to be expanded. The results show, however, that the investigated choices for pre-processing and parameter settings were successful, and that a Japanese blog corpus, which in many ways differs from those used in previous studies, can be a useful resource for medical vocabulary expansion. PMID- 27671205 TI - Acute breathing patterns in healthy and heart disease participants during cycling at different levels of immersion. AB - We aimed to determine the effect of aquatic cycling and different levels of immersion on respiratory responses in healthy and heart disease (HD) volunteers. Thirty-four age matched volunteers, 21 HD and 13 healthy controls (HC) took part in this study. The ventilatory pattern, phase 1VE and steady-state ventilatory responses to progressive exercise from 40 to peak rpm, were measured while participants exercised on a water stationary bike (WSB) at different levels of immersion. No effect of immersion was observed on steady-state respiratory responses in the HD group, but immersion reduced VE phase 1 by ~79% at pedaling cadences of 40, 50 and 60rpm. In conclusion, immersion at hips and xiphoid process blunted the fast drive to breathe in the HD group. This transient effect on the respiratory response to immersed exercise cannot be considered a contraindication for exercise in HD individuals. PMID- 27671206 TI - Isolated endosalpingiosis of the appendix in an adolescent girl. PMID- 27671207 TI - [Male breast cancer in Morocco: Epidemiology and prognostic factors. A report of 140 cases]. AB - OBJECTIVES: Male breast cancer is rare; it constitutes 0.2-1.5 % of all malignant tumors in men and 1 % of all breast cancers. METHODS: The goal of this retrospective study is to analyze the epidemiologic, clinic, therapeutic and evolutive profiles of this disease in 140 cases collected at the National Institute of Oncology and military hospital in Rabat, Morocco, between the years 1998 and 2007. RESULTS: The mean age was 61 years. A high incidence of overweight was found. The most frequent clinical presentation was a firm subareolar lump in 83 % of cases. The most common pathological type was an infiltrating ductal carcinoma (93 %). Hormone receptors were positive in 86 % of cases. Eighty-five percent of patients underwent simple mastectomy and axillary dissection, 68 % chest wall irradiation after surgery, 54 % received chemotherapy and 82 % hormonal therapy. Median follow-up was 91.1 months. The estimated 5-year and 10 year overall survival was respectively 68 % and 74 %. CONCLUSION: The management of male and female breast carcinoma is the same, as well as their prognosis at equal stages. Future research for better understanding of this disease are needed to improve the management and prognosis of male patients. PMID- 27671208 TI - Induction of tolerance to different types of fish through desensitization with hake. PMID- 27671209 TI - Anatomical versus non-anatomical resection for solitary hepatocellular carcinoma without macroscopic vascular invasion: A propensity score matching analysis. AB - BACKGROUND AND AIM: The superiority of anatomical resection (AR) in patients with hepatocellular carcinoma compared with non-anatomical resection (NAR) remains controversial. We aimed to investigate the prognostic outcomes of AR and NAR for solitary hepatocellular carcinoma (HCC) patients without macroscopic vascular invasion, using a propensity score matching (PSM) analysis. METHODS: A total of 305 consecutive HCC patients without macroscopic vascular invasion who underwent curative hepatectomy were included in our study. PSM was performed in order to eliminate possible selection bias. RESULTS: By PSM, the patients were divided into propensity-matched anatomical resection (PS-AR) (n = 114) and propensity matched non-anatomical resection (PS-NAR) (n = 114) groups. The 1-year, 3-year, and 5-year overall survival rates were 90.4%, 77.7%, and 65.7% in PS-AR and 88.6%, 70.7%, and 52.2% in PS-NAR (P = 0.053), respectively. The 1-year, 3-year, and 5-year recurrence-free survival (RFS) rates were 84.1%, 64.9%, and 45.1% in PS-AR and 75.4%, 48.1%, and 31.0% in PS-NAR (P = 0.005), respectively. Multivariate analysis showed that ICG-R15 (P = 0.022); the Barcelona clinic liver cancer staging (P = 0.044) and microvascular invasion (MVI; P = 0.005) were independent risk factors for the overall survival rate, while type of resection (P = 0.027), surgical margin (P = 0.039), and MVI (P = 0.024) were independent risk factors for the RFS rate. Patients who underwent NAR were prone to early recurrence and marginal recurrence. Subgroup analysis indicated that the RFS rate was significantly better in PS-AR than that in PS-NAR (surgical margin >= 1 cm) (P = 0.025). Better RFS rate was observed in PS-AR with MVI compared with PS-NAR (P = 0.016). CONCLUSIONS: Anatomical resection contributed to improve the RFS rate in solitary HCC patients without macroscopic vascular invasion using PSM analysis, especially in patients with MVI. PMID- 27671210 TI - Orthographic and phonological processing in developing readers revealed by ERPs. AB - The development of neurocognitive mechanisms in single word reading was studied in children ages 8-10 years using ERPs combined with priming manipulations aimed at dissociating orthographic and phonological processes. Transposed-letter (TL) priming (barin-BRAIN vs. bosin-BRAIN) was used to assess orthographic processing, and pseudohomophone (PH) priming (brane-BRAIN vs. brant-BRAIN) was used to assess phonological processing. Children showed TL and PH priming effects on both the N250 and N400 ERP components, and the magnitude of TL priming correlated positively with reading ability, with better readers showing larger TL priming effects. Phonological priming, on the other hand, did not correlate with reading ability. The positive correlations between TL priming and reading ability in children points to a key role for flexible sublexical orthographic representations in reading development, in line with their hypothesized role in the efficient mapping of orthographic information onto semantic information in skilled readers. PMID- 27671211 TI - Stretch Injury of Human Induced Pluripotent Stem Cell Derived Neurons in a 96 Well Format. AB - Traumatic brain injury (TBI) is a major cause of mortality and morbidity with limited therapeutic options. Traumatic axonal injury (TAI) is an important component of TBI pathology. It is difficult to reproduce TAI in animal models of closed head injury, but in vitro stretch injury models reproduce clinical TAI pathology. Existing in vitro models employ primary rodent neurons or human cancer cell line cells in low throughput formats. This in vitro neuronal stretch injury model employs human induced pluripotent stem cell-derived neurons (hiPSCNs) in a 96 well format. Silicone membranes were attached to 96 well plate tops to create stretchable, culture substrates. A custom-built device was designed and validated to apply repeatable, biofidelic strains and strain rates to these plates. A high content approach was used to measure injury in a hypothesis-free manner. These measurements are shown to provide a sensitive, dose-dependent, multi-modal description of the response to mechanical insult. hiPSCNs transition from healthy to injured phenotype at approximately 35% Lagrangian strain. Continued development of this model may create novel opportunities for drug discovery and exploration of the role of human genotype in TAI pathology. PMID- 27671212 TI - Developmental change in translation initiation alters the localization of a common microbial protein necessary for Toxoplasma chronic infection. AB - The Toxoplasma gondii cyst stage is resistant to drug therapy. To identify potential targets for new therapeutics, we screened insertional mutants of T. gondii for a reduced ability to form cysts in the brains of mice. In one of these mutants, named 38C3, the mutagenesis plasmid inserted into the mRNA of a protein that is highly conserved in microbes but is not present in humans. The mutation in 38C3 causes reduced brain cyst production during chronic infection, but does not affect acute virulence, so the disrupted gene and protein are called T. gondii Brain Colonization Protein 1 (TgBCP1). TgBCP1 has three potential in frame start codons that produce 51, 33 or 25 kDa proteins. In rapidly replicating tachyzoites, translation initiates at the third methionine, producing the 25 kDa form that is conserved in many bacteria and protozoans. Brain cysts exclusively express the 51 kDa form of TgBCP1, which is secreted from the parasites and localizes to the cyst wall. Only expression of the long form of TgBCP1 restored cyst formation in the 38C3 mutant. TgBCP1 is essential for cyst formation and is the first example of a developmental regulation in translation initiation site preference for a T. gondii protein. PMID- 27671213 TI - Genome-wide association and replication study of anti-tuberculosis drugs-induced liver toxicity. AB - BACKGROUND: Drug-induced liver injury (DILI) is a well-recognized adverse event of anti tuberculosis drugs (ATD) possibly associated with genetic variations. The objective of this study was to perform genome-wide association study (GWAS) to identify genetic variants associated with the risk for ATD induced liver toxicity in Ethiopian patients. RESULT: Treatment-naive newly diagnosed tuberculosis patients (n = 646) were enrolled prospectively and treated with rifampicin based short course anti-tuberculosis therapy. Whole genome genotyping was done using Illumina Omni Express Exome Bead Chip genotyping array with 951,117 single nucleotide polymorphisms (SNPs) on 48 DILI cases and 354 ATD tolerants. Replication study was carried out for 50 SNPs with the lowest P-values (top SNPs) using an independent cohort consisting of 27 DILI cases and 217 ATD tolerants. In the combined analysis, the top SNP identified was rs10946737 (P = 4.4 * 10-6, OR = 3.4, 95 % confidence interval = 2.2-5.3) in the intron of FAM65B in chromosome 6. In addition, we identified a cluster of SNPs with suggestive genome-wide significance in the intron of ATP/GTP binding protein-like 4 (AGBL4). CONCLUSION: We identified genetic variants that are potentially associated with ATD induced liver toxicity. Further studies with larger sample sizes are essential to confirm the findings. PMID- 27671215 TI - Short- and Medium-Term Effects of Combined Mitral Valve Surgery and Coronary Artery Bypass Grafting Versus Coronary Artery Bypass Grafting Alone for Patients with Moderate Ischemic Mitral Regurgitation: A Meta-Analysis. AB - OBJECTIVE: To investigate the short- and medium-term effects of combined mitral valve surgery (MVS) and coronary artery bypass grafting (CABG) versus CABG alone for patients with moderate ischemic mitral regurgitation (IMR). DESIGN: Meta analysis of 4 randomized controlled trials (RCTs) and 5 observational studies. SETTING: Hospitals that perform cardiac surgery. PARTICIPANTS: The study included 1,256 cardiac surgery patients from 4 RCTs and 5 observational studies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four RCTs and 5 observational studies were included in this meta-analysis. Concomitant MVS significantly reduced the residual rate of postoperative IMR (moderate or severe) (RCTs: OR 0.32, 95% confidence interval [CI] -0.58 to -0.07, p = 0.01; observational studies: OR -0.23, 95% CI -0.34 to -0.12, p<0.0001) and the proportion of surviving patients with New York Heart Association class III or IV (RCTs: OR 0.45, 95% CI 0.31-1.8, p = 0.008), but did not improve early mortality (RCTs: OR 0.91, 95% CI 0.30-2.74, p = 0.87; observational studies: OR 1.63, 95% CI 0.88 3.05, p = 0.12) or medium-term mortality (RCTs: OR 0.89, 95% CI 0.46-1.74, p = 0.73; observational studies: OR 0.94, 95% CI 0.65-1.37, p = 0.48) compared with CABG alone. Moreover, adding the mitral valve procedure did not significantly increase the risk of stroke (RCTs: OR 2.27, 95% CI 0.73-7.08, p = 0.16; observational studies: OR 0.55, 95% CI 0.10-3.06, p = 0.50). CONCLUSIONS: The potential benefits of combined MVS and CABG could outweigh its risks for patients with moderate IMR. PMID- 27671214 TI - Structural characterization reveals a novel bilobed architecture for the ectodomains of insect stage expressed Trypanosoma brucei PSSA-2 and Trypanosoma congolense ISA. AB - African trypanosomiasis, caused by parasites of the genus Trypanosoma, is a complex of devastating vector-borne diseases of humans and livestock in sub Saharan Africa. Central to the pathogenesis of African trypanosomes is their transmission by the arthropod vector, Glossina spp. (tsetse fly). Intriguingly, the efficiency of parasite transmission through the vector is reduced following depletion of Trypanosoma brucei Procyclic-Specific Surface Antigen-2 (TbPSSA-2). To investigate the underlying molecular mechanism of TbPSSA-2, we determined the crystal structures of its ectodomain and that of its homolog T. congolense Insect Stage Antigen (TcISA) to resolutions of 1.65 A and 2.45 A, respectively using single wavelength anomalous dispersion. Both proteins adopt a novel bilobed architecture with the individual lobes displaying rotational flexibility around the central tether that suggest a potential mechanism for coordinating a binding partner. In support of this hypothesis, electron density consistent with a bound peptide was observed in the inter-lob cleft of a TcISA monomer. These first reported structures of insect stage transmembrane proteins expressed by African trypanosomes provide potentially valuable insight into the interface between parasite and tsetse vector. PMID- 27671216 TI - Low-Cardiac-Output Syndrome After Cardiac Surgery. PMID- 27671217 TI - Defining Quality Markers for Cardiac Anesthesia: What, Why, How, Where to, and Who's on Board? PMID- 27671218 TI - Anesthetic Management of Transapical Off-Pump Mitral Valve Repair With NeoChord Implantation. AB - OBJECTIVES: Various minimally invasive surgical approaches have been used in mitral valve (MV) surgery. The transapical off-pump mitral valve intervention with NeoChord implantation (TOP-MINI) is a minimally invasive, alternative procedure for the treatment of degenerative mitral regurgitation. There are several special considerations for the anesthesiologist during the TOP-MINI procedure. The main purpose of this study was to present the anesthetic management of the TOP-MINI procedure. DESIGN: An observational study. SETTING: Training and research hospital. PARTICIPANTS: Adult patients who underwent MV repair with the NeoChord DS1000 system (NeoChord Inc, St Louis Park, MN). INTERVENTIONS: The study included 12 consecutive patients who underwent MV repair with the NeoChord DS1000 system at the Antalya Training and Research Hospital, Antalya, Turkey, between June 2014 and December 2015. A record was made of preoperative demographic details, comorbidities, preoperative and postoperative mitral regurgitation severity, preoperative and postoperative forced expiratory volume in 1 second values, use of blood products and vasoactive drugs, surgical times, mechanical ventilation times, intensive care unit (ICU) and hospital length of stay, visual analog scale scores, analgesic requirement in ICU and perioperative complications. MEASUREMENTS AND MAIN RESULTS: TOP-MINI was performed completely off-pump in 12 patients. Intraoperative salvaged blood via cell-saver was 660+/-196 mL. Patients required 0.8+/-0.7 U of red blood cells and 2.0+/-0.9 U of fresh frozen plasma in the ICU. Inotropic support was used in 5 patients. There was a significant decline in mean arterial pressure from before surgery to during implantation (70.9+/-4.5 mmHg v 51.7+/-5.8 mmHg, respectively). A statistically significant increase was demonstrated in mean arterial pressure from during implantation to postimplantation (51.7+/-5.8 mmHg v 67.0+/-6.8 mmHg, respectively). There were no significant differences in preoperative and postoperative forced expiratory volume in 1 second values. Defibrillation was required in 1 patient, and temporary atrial fibrillation was observed in 1 patient during the procedure. Atelectasis occurred in the postoperative period in 1 patient. The mean visual analog scale score was 3.6+/-1.4, and the mean tramadol consumption was 77+/-39 mg in the ICU. Extubation time and the mean length of stay in the ICU and hospital were 2.6+/-0.5 hours, 19.8+/-2.7 hours, 5+/-1 days, respectively. CONCLUSIONS: The TOP-MINI procedure requires complex anesthetic management. Transesophageal echocardiographic guidance is essential for this procedure. One-lung ventilation, fluid administration, avoidance of hypothermia, and pain management are the bases for anesthetic management. PMID- 27671219 TI - Epidemiological and genetic analysis of hand-foot-mouth disease by enterovirus A71 in Taizhou, P. R. China, between 2010 and 2013. AB - Out of a population of 1,098 enteroviruses (EVs)-positive hand, foot, and mouth disease (HFMD) specimens, 352 were screened positive for EV-A71-accounting for 32.1% of all EV-positive specimens. This percentage denotes EV-A71 as the second major serotype of enteroviruse among HFMD suffers in Taizhou. An epidemic outbreak of EV-A71 among HFMD children was found in Taizhou in the second quarter of 2012. Phylogeny analysis based on the VP1 complete sequences leads us to find a sub-clade (designated TZ1-1) of EV-A71 circulating in Taizhou, whose emergence might be correlated with the epidemic outbreak. This correlation was further supported by the followed two analyses (namely skyline plot of population history and birth-death SIR simulation of epidemic history). And more importantly, at a positively selected site of VP1 caspid, a mutation of N31D was found to be a synapomorphy of TZ1-1 and its occurrence might be correlated with the epidemic outbreak. J. Med. Virol. 89:782-790, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27671220 TI - Acquired resistance to chlorhexidine - is it time to establish an 'antiseptic stewardship' initiative? AB - Chlorhexidine digluconate (CHG) is an antimicrobial agent used for different types of applications in hand hygiene, skin antisepsis, oral care, and patient washing. Increasing use raises concern regarding development of acquired bacterial resistance. Published data from clinical isolates with CHG minimum inhibitory concentrations (MICs) were reviewed and compared to epidemiological cut-off values to determine resistance. CHG resistance is rarely found in Escherichia coli, Salmonella spp., Staphylococcus aureus or coagulase-negative staphylococci. In Enterobacter spp., Pseudomonas spp., Proteus spp., Providencia spp. and Enterococcus spp., however, isolates are more often CHG resistant. CHG resistance may be detected in multi-resistant isolates such as extremely drug resistant Klebsiella pneumoniae. Isolates with a higher MIC are often less susceptible to CHG for disinfection. Although cross-resistance to antibiotics remains controversial, some studies indicate that the overall exposure to CHG increases the risk for resistance to some antibiotic agents. Resistance to CHG has resulted in numerous outbreaks and healthcare-associated infections. On an average intensive care unit, most of the CHG exposure would be explained by hand hygiene agents when liquid soaps or alcohol-based hand rubs contain CHG. Exposure to sub-lethal CHG concentration may enhance resistance in Acinetobacter spp., K. pneumoniae, and Pseudomonas spp., all species well known for emerging antibiotic resistance. In order to reduce additional selection pressure in nosocomial pathogens it seems to make sense to restrict the valuable agent CHG to those indications with a clear patient benefit and to eliminate it from applications without any benefit or with a doubtful benefit. PMID- 27671221 TI - The housefly Musca domestica as a mechanical vector of Clostridium difficile. AB - BACKGROUND: Clostridium difficile is a bacterial healthcare-associated infection that may be transferred by houseflies (Musca domestica) due to their close ecological association with humans and cosmopolitan nature. AIM: To determine the ability of M. domestica to transfer C. difficile both mechanically and following ingestion. METHODS: M. domestica were exposed to independent suspensions of vegetative cells and spores of C. difficile, then sampled on to selective agar plates immediately postexposure and at 1-h intervals to assess the mechanical transfer of C. difficile. Fly excreta was cultured and alimentary canals were dissected to determine internalization of cells and spores. FINDINGS: M. domestica exposed to vegetative cell suspensions and spore suspensions of C. difficile were able to transfer the bacteria mechanically for up to 4h upon subsequent contact with surfaces. The greatest numbers of colony-forming units (CFUs) per fly were transferred immediately following exposure (mean CFUs 123.8 +/- 66.9 for vegetative cell suspension and 288.2 +/- 83.2 for spore suspension). After 1h, this had reduced (21.2 +/- 11.4 for vegetative cell suspension and 19.9 +/- 9 for spores). Mean C. difficile CFUs isolated from the M. domestica alimentary canal was 35 +/- 6.5, and mean C. difficile CFUs per faecal spot was 1.04 +/- 0.58. C. difficile could be recovered from fly excreta for up to 96h. CONCLUSION: This study describes the potential for M. domestica to contribute to environmental persistence and spread of C. difficile in hospitals, highlighting flies as realistic vectors of this micro-organism in clinical areas. PMID- 27671222 TI - A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery. AB - The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed. PMID- 27671224 TI - Can we document the practice of dispensing? A systematic review. AB - WHAT IS KNOWN: Documentation is a process indicator utilized to evaluate quality clinical pharmacist services. In this framework, documentation of dispensing, besides supporting patient care, allows evaluation of the impact of counselling. OBJECTIVE: To identify and assess studies of documentation by pharmacists in the dispensing process. METHOD: A systematic review was carried out according to the following steps: (i) identification of studies in the following databases: PubMed/Medline, Web of Science, Scopus and Lilacs, using the descriptors 'counselling', 'dispensing', 'community pharmacy services', 'pharmacies' and 'pharmacists' in different combinations; (ii) evaluation of studies, in which the title, abstract and full text of the studies, and the evaluation of the methodological quality of the selected studies were analysed. RESULTS: In total, 26 articles met the specific criteria. Few studies addressed documentation as part of the dispensing working process (3), and 16 articles reported documentation using non-electronic systems. The main variables documented were patient information, drug therapy problems and clinical interventions. Furthermore, 20 studies showed the effects of documentation in the dispensing process and 23 studies included statistical evidence. Eight articles met between 42% and 75% of the 28 items recommended by the STROBE initiative, and two articles met approximately 60% of the 36 items recommended by the CONSORT initiative. WHAT IS NEW AND CONCLUSION: Few studies address documentation as part of the dispensing working process. Thus, researchers should be concerned with standardizing documentation and implementing more robust designs and multicenter studies. PMID- 27671223 TI - Cost of treatment of peripheral neuropathic pain with pregabalin or gabapentin in routine clinical practice: impact of their loss of exclusivity. AB - To analyze the effect of loss of exclusivity of data on the cost of treatment of peripheral neuropathic pain (PNP) with pregabalin or gabapentin in routine clinical practice. A retrospective observational study, with electronic medical records for patients enrolled at primary care centers managed by the health care provider Badalona Serveis Assistencials, who initiated treatment of PNP with pregabalin or gabapentin. The analysis used drugs and resources prices for year 2015. The 1163 electronic medical records (pregabalin; N = 764, gabapentin; N = 399) for patients (62.2% women) with a mean (standard deviation) age of 59.2 (14.7) years were analyzed. Treatment duration was slightly shorter with pregabalin than with gabapentin (5.2 vs 5.5 months; P = 0.124), with mean doses of 227.4 (178.6) mg and 900.0 (443.4) mg, respectively. The average study drug cost per patient was higher for pregabalin than for gabapentin; ?214.6 (206.3) vs ?157.4 (181.9), P < 0.001, although the cost of concomitant analgesic medication was lower; ?176.5 (271.8) vs ?306.7 (529.2), P < 0.001. The adjusted average total cost per patient was lower in those treated with pregabalin than in those treated with gabapentin; ?2,413 (2119-2708) vs ?3201 (2806-3.597); P = 0.002, owing to significantly lower health care costs; ?1307 (1247-1367) vs ?1538 (1458 1618), P < 0.001, and also non-health care costs; ?1106 (819-1393) vs ?1663 (1279 2048), P = 0.023, that was caused by a significantly lower use of concomitant medication, fewer medical visits to primary care, and fewer days of sick leave. After loss of exclusivity of both drugs, pregabalin continued to show lower health care and non-health care costs than gabapentin in the treatment of PNP in routine clinical practice. PMID- 27671225 TI - Fulminant respiratory failure due to progressive metastatic pulmonary calcification with no predisposing factors after successful renal transplantation: A case report. AB - We report the patient with MPC who developed fulminant respiratory failure that leads to death with no predisposing factors after successful renal transplantation. In addition to infectious diseases, MPC should be kept in mind when post-transplantation patients develop pulmonary symptoms. The majority of the patients with MPC are asymptomatic; however, some patients develop fulminant respiratory failure and may progress to death. MPC can develop or progress in patients with no predisposing factors after successful renal transplantation. PMID- 27671226 TI - The critical role of mast cell-derived hypoxia-inducible factor-1alpha in regulating mast cell function. AB - OBJECTIVES: During colorectal tumour progression, the tumour microenvironment becomes hypoxic, and infiltration of a large number of inflammatory cells occurs. The mast cells (MCs) are a type of immune cells plays an important role in tumour angiogenesis. However, it is unclear whether the role of MC in colorectal cancer is to promote or to inhibit tumour growth. METHODS: Immunohistochemical analysis of clinical colorectal cancer samples and a colorectal carcinoma model were used. KEY FINDINGS: We found the carcinomas and the adjacent tissues were infiltrated with large numbers of mast cells, and the MC infiltration quantity increased with the Dukes' stage. After tumour inoculation, the survival time of MC-deficient mice was remarkably longer than wild-type C57BL/6 mice, and the tumour growth rate of MC-deficient mice was slower than wild type. In addition, the survival time and tumour growth rate can be recovered in MC reconstruction mice. Furthermore, inhibition of the expression of hypoxia-inducible factor-1alpha (HIF 1alpha) using siRNA reduced the release of inflammatory factors and the degree of MC degranulation. CONCLUSIONS: Mast cells promote the development of colorectal cancer, and MC-derived HIF-1alpha plays an important role in regulating MC function. Our study reveals a novel role of MC-derived HIF-1alpha in the colorectal carcinoma microenvironment. PMID- 27671227 TI - Generation of Janus kinase 1 (JAK1) conditional knockout mice. AB - The biological functions of the Janus kinase 1 (JAK1) are suggested to be pleiotropic since this signal transducer is ubiquitously expressed and coupled to a variety of cytokine receptors. Consequently, mice that are deficient in this tyrosine kinase were reported to die shortly after birth. To facilitate studies that address the biological and molecular functions of JAK1 during postnatal development, we performed gene targeting in embryonic stem cells and generated a Cre/lox-based conditional knockout mouse model. Expression of Cre recombinase in the germline converted the Jak1 conditional knockout allele (Jak1fl ) into a null allele (Jak1- ) that when subsequently crossed into homozygosity led to a complete absence of the JAK1 protein in developing embryos. JAK1 deficient embryos were visibly smaller starting at E15.5. Newborn pups exhibited signs of apnea and died within hours after birth. The examination of fibroblasts from conditional knockout embryos and their littermate wildtype controls expressing JAK1 showed that lack of this Janus kinase resulted in an impaired tyrosine phosphorylation and activation of the downstream Signal Transducers and Activators of Transcription (STATs) 1, 3, and 6. JAK1 conditional knockout mice will be an invaluable tool to study cytokine signaling during normal development and disease progression in adult animals. PMID- 27671228 TI - Neuroprotective effects of fingolimod in mouse models of Parkinson's disease. AB - Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons with limited treatment options. Emerging evidence shows that FTY720 protects against neural injury via modulation of the sphingosine-1-phosphate 1 receptor (S1PR1). However, it remains unclear whether FTY720 could influence neurodegeneration in PD. Therefore, the present study was designed to determine the impact of fingolimod (FTY720), a sphingosine-1-phosphate receptor (S1PR) agonist, on 2 mouse models of PD. We found that FTY720 significantly reduced the deficit of motor function, diminished the loss of tyrosine hydroxylase-positive neurons in the substantia nigra, and attenuated the decrease of striatal dopamine and metabolite levels in mice receiving 6-hydroxydopamine (6-OHDA) or rotenone to simulate PD. An S1PR1-selective antagonist, W146, blocked the neuroprotective effects of FTY720. Of note, FTY720 retained the phosphorylation of ERK, together with a decreased expression of cleaved caspase-3 in mice treated with 6-OHDA or rotenone. In vitro studies revealed that FTY720 also attenuated 6-OHDA- or rotenone-induced toxicity in SH-SY5Y cells. These findings suggest the potential of S1PR modulation as a treatment for PD.-Zhao, P., Yang, X., Yang, L., Li, M., Wood, K., Liu, Q., Zhu, X. Neuroprotective effects of fingolimod in mouse models of Parkinson's disease. PMID- 27671229 TI - Intraluminal delivery of thrombospondin-2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model. AB - In an effort to inhibit the response to vascular injury that leads to intimal hyperplasia, this study investigated the in vivo efficacy of intraluminal delivery of thrombospondin-2 (TSP-2) small interfering RNA (siRNA). Common carotid artery (CCA) balloon angioplasty injury was performed in rats. Immediately after denudation, CCA was transfected intraluminally (15 min) with one of the following: polyethylenimine (PEI)+TSP-2 siRNA, saline, PEI only, or PEI+control siRNA. CCA was analyzed at 24 h or 21 d by using quantitative real time PCR and immunohistochemistry. TSP-2 gene and protein expression were significantly up-regulated after endothelial denudation at 24 h and 21 d compared with contralateral untreated, nondenuded CCA. Treatment with PEI+TSP-2 siRNA significantly suppressed TSP-2 gene expression (3.1-fold) at 24 h and TSP-2 protein expression, cell proliferation, and collagen deposition up to 21 d. These changes could be attributed to changes in TGF-beta and matrix metalloproteinase 9, the downstream effectors of TSP-2. TSP-2 knockdown induced anti-inflammatory M2 macrophage polarization at 21 d; however, it did not significantly affect intima/media ratios. In summary, these data demonstrate effective siRNA transfection of the injured arterial wall and provide a clinically effective and translationally applicable therapeutic strategy that involves nonviral siRNA delivery to ameliorate the response to vascular injury.-Bodewes, T. C. F., Johnson, J. M., Auster, M., Huynh, C., Muralidharan, S., Contreras, M., LoGerfo, F. W., Pradhan-Nabzdyk, L. Intraluminal delivery of thrombospondin-2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model. PMID- 27671230 TI - Prognosis of Medullary Carcinoma of the Breast: 10 years' Experience in a Single Institution. PMID- 27671231 TI - Sanguisorba officinalis L synergistically enhanced 5-fluorouracil cytotoxicity in colorectal cancer cells by promoting a reactive oxygen species-mediated, mitochondria-caspase-dependent apoptotic pathway. AB - Sanguisorba officinalis L. radix is a widely used herb called DiYu (DY) in China and has an extensive range of bioactivities, including anti-cancer, anti inflammatory, and anti-oxidative activities. However, there is little evidence to support its anti-cancer effects against colorectal cancer (CRC). The first-line chemotherapeutic agent 5-fluorouracil (5-FU) is used to treat CRC, but its efficiency is hampered by acquired drug resistance. This study found that a water extract of DY exerted anti-proliferative effects against two CRC cell lines (HCT 116 and RKO), and it sensitized CRC cells to 5-FU therapy by activating a reactive oxygen species (ROS)-mediated, mitochondria-caspase-dependent apoptotic pathway. Co-treatment of DY and 5-FU significantly elevated ROS levels, up regulated Bax/Bcl-2 ratio and triggered mitochondrial dysfunction, followed by a release of cytochrome c and up-regulation of proteins such as cleaved-caspase-9/3 and cleaved-PARP. Additionally, the induction of autophagy may be involved in mediating synergism of DY in HCT-116 cells. Gallic acid (GA), catechinic acid (CA) and ellagic acid (EA) were identified as the potential chief constituents responsible for the synergistic effects of DY. In conclusion, co-treatment of DY, specifically GA, CA and EA, with 5-FU may be a potential alternative therapeutic strategy for CRC by enhancing an intrinsic apoptotic pathway. PMID- 27671232 TI - KLF4 Knockdown Attenuates TBI-Induced Neuronal Damage through p53 and JAK-STAT3 Signaling. AB - AIMS: Traumatic brain injury (TBI) is induced by complex primary and secondary mechanisms that give rise to cell death, inflammation, and neurological dysfunction. Understanding the mechanisms that drive neurological damage as well as those that promote repair can guide the development of therapeutic drugs for TBI. Kruppel-like factor 4 (KLF4) has been reported to negatively regulate axon regeneration of injured retinal ganglion cells (RGCs) through inhibition of JAK STAT3 signaling. However, the role of KLF4 in TBI remains unreported. Reactive oxygen species (ROS)-induced neuronal death is a pathophysiological hallmark of TBI. METHODS: In this study, we used H2 O2 -treated RGCs in vitro and the optic nerve crush model in vivo to simulate neuronal damage in TBI. The function of KLF4 in RGC survival and axon regeneration in these models was investigated. In addition, the effects of KLF4 knockdown on neuronal damage after a brain impact that mimics moderate TBI were studied. RESULTS: The results show that H2 O2 induces p53-dependent apoptosis of RGCs in vitro through upregulation of KLF4. Additionally, KLF4 knockdown in vivo significantly enhances CNTF-induced axon regeneration of RGCs after optic nerve crush, and more importantly, prevents neuronal damage after a moderate brain impact in rats. Our Western blot analysis and immunoprecipitation assay results indicate that these effects of KLF4 knockdown are mediated by the p53 and JAK-STAT3 pathways. CONCLUSION: These findings provide evidence that KLF4 plays an important role in the pathophysiology of TBI. Blocking KLF4 may be a potential therapeutic strategy for the treatment of TBI, either alone or in combination with agents that target complementary mechanisms. PMID- 27671233 TI - Theoretical Study of the Adsorption Mechanism of Cystine on Au(110) in Aqueous Solution. AB - The adsorption and dynamics of cystine, which is the oxidized dimer of cysteine where the monomers are connected through a disulfide bond, on the Au(110) surface, in water solution, is characterized by means of classical molecular dynamics simulations based on a recently developed reactive force field (ReaxFF). The adopted computational procedure and the force field description are able to give a complete and reliable picture, in line with experiments, of the molecule behavior in solution and in close contact with the metal support. Many different aspects, which have never been explored computationally at this level of theory, are disclosed, namely, physisorption, chemisorption, disulfide bridge breaking/creation, and formation of staples. It is demonstrated that all these events are connected with the specific orientation and location of cystine on the substrate. Simulations in pure water reveal that the disulfide bridge is stable, whereas dissociation is observed on gold. This is favored at low coverage, whereas at high coverage both intact and dissociated forms can be observed depending on local arrangements. The computed photoemission spectra at different K-edges for the predicted adsorbate structures satisfactorily agree with the experimental measurements extracted from literature. PMID- 27671234 TI - Characterization of Water and a Model Lipophilic Compound in Human Stratum Corneum by NMR Spectroscopy and Equilibrium Sorption. AB - The stratum corneum (SC) is the outermost skin layer in humans and other mammals and the primary barrier to water loss and environmental exposure to chemicals and microorganisms. It consists of flattened, keratin-filled corneocytes surrounded by well-organized lipid layers. Human SC at varying degrees of hydration with and without addition of a model lipophilic compound, 2-(trifluoromethyl) benzonitrile (TFMB), was studied using proton (1H) and fluorine (19F) nuclear magnetic resonance techniques. Proton spectral analyses revealed that water mainly occupies the corneocytes in agreement with prior studies. Observations from 19F spectral and spin-lattice relaxation time (T1) analyses showed that TFMB is primarily present in the lipids with small amounts in water, which is located within the corneocytes. This is consistent with TFMB sorption, which was measured in SC with and without lipid extraction. The presence of TFMB within the corneocytes supports the hypothesis that transcellular diffusion of a lipophilic compound like TFMB may contribute to SC permeation. PMID- 27671235 TI - Lung Retention by Lysosomal Trapping of Inhaled Drugs Can Be Predicted In Vitro With Lung Slices. AB - Modulating and optimizing the local pharmacokinetics of inhaled drugs by chemical design or formulation is challenged by the lack of predictive in vitro systems and in vivo techniques providing a detailed description of drug location in the lung. The present study investigated whether a new experimental setup of freshly prepared agarose-filled lung slices can be used to estimate lung retention in vitro, by comparing with in vivo lung retention after intratracheal instillation. Slices preloaded with inhaled beta-adrenergic compounds (salbutamol, formoterol, salmeterol, indacaterol or AZD3199) were incubated in a large volume of buffer (w/wo monensin to assess the role of lysosomal trapping), and the amount remaining in slices at different time points was determined with liquid chromatography-tandem mass spectrometry. The in vitro lung retention closely matched the in vivo lung retention (half-lives within 3-fold for 4/5 compounds), and monensin shortened the half-lives for all compounds. The results suggest that freshly prepared rat lungs slices can be used to predict lung retention and that slow kinetics of lysosomal trapping is a key mechanism by which retention in the lung and the effect duration of inhaled beta-adrenergic bronchodilators are prolonged. PMID- 27671236 TI - Microdialysis of Large Molecules. AB - Microdialysis is a validated and well-established technique for recovering and measurement of exogenous as well as endogenous small molecules in the interstitial spaces of various tissues. Microdialysis of large molecular weight compounds has become possible due to the availability of large molecular weight cutoff membranes and is being explored extensively. There are increasing reports of successful recovery of large molecules such as proteins, cytokines, and neuropeptides using microdialysis. This is not only useful for studying protein expression but also for clinical evaluation of disease biomarkers in different tissues. Large pore microdialysis along with open flow microperfusion offers great promise in determining interstitial tissue concentrations of therapeutic proteins including monoclonal antibodies and helps in understanding their pharmacokinetic-pharmacodynamic relationship. PMID- 27671237 TI - Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients and the Application in Dosing Recommendation. AB - Our previous study indicates that cerebrospinal fluid (CSF) albumin level is a determinant of CSF vancomycin concentration for postoperative neurosurgical patients. We aimed to develop an improved vancomycin population pharmacokinetic model with incorporation of more covariates, and to provide dosing guidance for clinicians. Vancomycin was administered intravenously to 20 patients with external ventricular drains after neurosurgical operation. Blood and CSF were collected and vancomycin concentrations were measured by HPLC. A separate CSF compartment was considered, and was linked to the central compartment by a first order process (QCSF). The clearance of the CSF compartment (ClCSF) was used to characterize vancomycin elimination from CSF through external ventricular drain. Nonlinear mixed-effects modeling approach was used to develop the model. The CSF albumin level (mg/dL) was the covariate influencing QCSF: QCSF=0.0049+0.000021*(CSF albumin-279). The effect of body weight (BW, kg) was significant on central volume (VC): VC=27.84+0.96*(BW-69). All parameters were estimated with an acceptable precision (relative standard error: RSE% < 30.26). The performance of the final model was acceptable with our previous dataset. A simple to use dosage regimen table was created to guide clinicians with vancomycin dosing. This model incorporates variables of both CSF albumin and BW, which offers improvements to the previous pharmacokinetics model. PMID- 27671238 TI - An Opportunity for Industry-Academia Partnership: Training the Next Generation of Industrial Researchers in Characterizing Higher Order Protein Structure. AB - Training researchers for positions in the United States biopharmaceutical industry has long been driven by academia. This commentary explores how the changing landscape of academic training will impact the industrial workforce, particularly with regard to the development of protein therapeutics in the area of biophysical and higher order structural characterization. We discuss how to balance future training and employment opportunities, how academic-industrial partnerships can help young scientists acquire the skills needed by their future employer, and how an appropriately trained workforce can facilitate the translation of new technology from academic to industrial laboratories. We also present suggestions to facilitate the coordinated development of industrial academic educational partnerships to develop new training programs, and the ability of students to locate these programs, through the development of authoritative public resources. PMID- 27671239 TI - Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling. AB - The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues' response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells' shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID- 27671240 TI - Adrenaline inhibits osteogenesis via repressing miR-21 expression. AB - Sympathetic signaling is involved in bone homeostasis; however, the cellular and molecular mechanisms remain unknown. In this study, we found that the psychological stress mediator adrenaline inhibited osteogenic differentiation of human bone marrow-derived stem cells (hMSC) by reducing microRNA-21 (miR-21) expression. Briefly, adrenaline significantly inhibited the osteogenic differentiation of hMSCs, as observed with both Alizarin red staining and maker gene expression (RUNX2, OSX, OCN, and OPN). During this process, miR-21 was suppressed by adrenaline via inhibition of histone acetylation, as verified by H3K9Ac chromatin immunoprecipitation (ChIP) assay. MiR-21 was confirmed to promote hMSC osteogenic differentiation, and overexpression of miR-21 reversed the impeditive effect of adrenaline on hMSC osteogenic differentiation. Our results demonstrate that down-regulation of miR-21 is responsible for the adrenaline-mediated inhibition of hMSC osteogenic differentiation. These findings indicate a regulation of bone metabolism by psychological stress and also provide a molecular basis for psychological stress-associated bone diseases. PMID- 27671242 TI - Mitochondrial Membrane Protein-Associated Neurodegeneration Mimicking Juvenile Amyotrophic Lateral Sclerosis. AB - BACKGROUND: Mitochondrial membrane protein associated neurodegeneration (MPAN) is the third most common subtype of neurodegeneration with brain iron accumulation (NBIA) and caused by mutations of the orphan gene C19ORF12 encoding a transmembrane mitochondrial protein. Like other NBIA disorders, the hallmark of neuropathology is iron deposition in the basal ganglia, but the clinical presentation is highly variable. METHODS: We present the relevant clinical history, neurological examination, electrophysiological and neuroimaging tests of a currently ten-year-old girl. The genetic analysis was carried out by exome sequencing focused on known NBIA and juvenile amyotrophic lateral sclerosis (ALS) genes. RESULTS: The patient presented at four years of age with progressive lower extremity weakness and generalized hypotonia. She was initially diagnosed with juvenile ALS based on clinical signs, negative brain magnetic resonance imaging (MRI) and electromyography findings. As the disease progressed, a repeat brain MRI showed iron deposition in the basal ganglia at nine years of age. Exome sequencing of genes known to be associated with NBIA revealed a compound heterozygous mutation of C19ORF12 gene. CONCLUSIONS: A C19orf12 gene mutation should be considered in young children with clinical signs of progressive upper and lower motor neuron disease. Finding iron accumulation in the basal ganglia helps to focus the genetic testing, but it may not be apparent for several years. PMID- 27671244 TI - Erratum: Bona-fide method for the determination of short range order and transport properties in a ferro-aluminosilicate slag. PMID- 27671241 TI - Epilepsy Characteristics and Clinical Outcome in Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS). AB - BACKGROUND: Epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are heterogeneous with no pathognomonic features. We reviewed epilepsy characteristics and clinical outcome exclusively in a pediatric population. METHODS: Twenty-two children and adolescents (13 males) with confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA A3243G mutation and epilepsy were recruited. Clinical data including seizure semiology, treatment response, neuroimaging findings, and electroencephalography were analyzed. We also examined the effect of the age at seizure onset and initial symptoms on the clinical variables. RESULTS: Seizure semiology and electroencephalography abnormalities showed no syndrome-specific findings. Focal seizures occurred in 21 of 22 subjects (95.5%), whereas generalized seizures developed in seven of 22 subjects (31.8%). Twenty of 22 subjects (90.9%) achieved partial to complete reduction of clinical seizures for more than one year with a combination of more than two antiepileptic drugs. The subgroup with earlier seizure onset presented significantly earlier and showed significantly higher rates of drug-resistant epilepsy compared with the late onset group, although there were no significant differences in the initial symptoms. The subjects with severe epileptic conditions tended to have more severe clinical dysfunction and more severe organ involvement. CONCLUSIONS: Both focal and generalized seizures occurred in patients with MELAS. Epilepsy in this population is drug resistant, but a certain degree of clinical seizure reduction was achievable with antiepileptic drugs, with more favorable outcomes than historically expected. Close observation and active epilepsy treatment of individuals with MELAS episodes and earlier seizure onset might improve the prognosis. PMID- 27671243 TI - Systematically developed pilot randomized controlled trial of exercise and cognition in persons with multiple sclerosis. AB - Cognitive impairment is common and debilitating among persons with multiple sclerosis (MS) and might be managed with exercise training. The present pilot study adopted a single-blind randomized controlled trial (RCT) design and is the first to examine the effect of a systematically developed, progressive treadmill walking exercise training intervention on cognition among fully ambulatory persons with MS. Ten fully ambulatory females with MS were randomly assigned into exercise training intervention or waitlist control conditions. The intervention condition involved 12 weeks of supervised, progressive chronic treadmill walking exercise training. Participants underwent measures of cognition (i.e., cognitive processing speed (CPS), executive function), walking performance, and cardiorespiratory fitness before and after the 12-week period; baseline and follow-up assessments were performed by blinded assessors. Overall, there were large intervention effects on CPS (d = 0.95), walking performance (d = 0.76), and cardiorespiratory fitness (d > 1.08). The change in cardiorespiratory fitness was significantly associated with change in CPS (r = .60), but not walking performance. This small pilot RCT provides preliminary proof-of-concept data supporting progressive treadmill walking exercise training for potentially improving CPS, walking performance, and cardiorespiratory fitness in fully ambulatory persons with MS, and that improved fitness might be a possible mechanism for improved CPS. PMID- 27671245 TI - Treatment satisfaction among patients with psoriasis at a large academic center: an observational study. PMID- 27671248 TI - Osmolyte Effects on the Growth of Amyloid Fibrils. AB - Understanding the role of naturally occurring protective osmolytes, such as trimethylamine N-oxide (TMAO), in the growth of amyloid fibrils implicated in neurodegenerative diseases is important to prevent fibril growth. The effect of TMAO on the growth of amyloid fibrils formed by the Sup35 prion peptide NNQQNY is studied using molecular dynamics simulations. The free-energy surface for the growth of the protofibril shows three major basins, corresponding to the free state where the peptide is in solution, the docked state where the peptide in solution interacts with the surface of the protofibril, and the locked state where the peptide is tightly bound to the protofibril, becoming a part of the fibril. The free-energy surface in the presence of TMAO shows that TMAO stabilizes the locked state of the peptide compared with the free state, indicating that TMAO aids in fibril growth. Dissecting the interaction of TMAO with individual amino acids in the peptide shows that TMAO interacts both directly and indirectly with the amino acids, depending on the nature of the side chains. The methyl groups in TMAO interact strongly with the hydrophobic aromatic ring in the Tyr residue. In the locked state, the surface area of Tyr available for interaction with TMAO decreases; as a result, the Tyr residue in the peptide flips out from the locked position, increasing the fluctuations of the peptide locked in the protofibril. Such strong direct interactions of amino acids with TMAO destabilize the folded or aggregated states of proteins. The overall increased stability of the peptide locked in the protofibril by TMAO is due to entropic or indirect interactions with the backbone Asn and Gln residues, which form major components of the NNQQNY peptide. PMID- 27671247 TI - Stochastic resonance therapy induces increased movement related caudate nucleus activity. AB - OBJECTIVE: Whole-body vibration can be used to supplement canonical physical treatment. It is performed while probands stand on a vibrating platform. Therapeutic vibration can be generated as a stochastic vibratory pattern, referred to as stochastic resonance whole-body vibration (SR-WBV). Despite the widespread use of SR-WBV its neurophysiological mechanism is unclear. DESIGN: A randomized sham-controlled double-blinded trial was performed as a pilot study. The experimental group received 6 cycles of SR-WBV at a frequency of 7 Hz with the SR-Zeptor device, and the sham group received the same treatment at a frequency of 1 Hz. At baseline 1.5 T functional magnetic resonance imaging (fMRI) was performed in the resting state, together with a finger/foot tapping test. A second fMRI was carried out after SR-WBV as sham treatment in both groups. Subsequently, a second cycle of SR-WBV was performed as sham or verum with consecutive fMRI, followed by a final fMRI on day 2. SUBJECTS: Nineteen healthy volunteers were allocated to the experimental or sham group, respectively. RESULTS AND CONCLUSION: Analyses of specific effects revealed a significant treatment * time interaction effect (p < 0.05, small-volume corrected (SVC FWE corrected)) in the left caudate nucleus during intermediate difficulty when comparing pre- vs post-SR-WBV treatment in the verum group. This proof-of-concept study suggests the existence of cerebral effects of SR-WBV. PMID- 27671246 TI - Frontline Science: Defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1. AB - Sepsis is a heterogeneous syndrome comprising a highly diverse and dynamic mixture of hyperinflammatory and compensatory anti-inflammatory immune responses. This immune phenotypic diversity highlights the importance of proper patient selection for treatment with the immunomodulatory drugs that are entering clinical trials. To better understand the serial changes in immunity of critically ill patients and to evaluate the potential efficacy of blocking key inhibitory pathways in sepsis, we undertook a broad phenotypic and functional analysis of innate and acquired immunity in the same aliquot of blood from septic, critically ill nonseptic, and healthy donors. We also tested the ability of blocking the checkpoint inhibitors programmed death receptor-1 (PD-1) and its ligand (PD-L1) to restore the function of innate and acquired immune cells. Neutrophil and monocyte function (phagocytosis, CD163, cytokine expression) were progressively diminished as sepsis persisted. An increasing frequency in PD-L1+ suppressor phenotype neutrophils [low-density neutrophils (LDNs)] was also noted. PD-L1+ LDNs and defective neutrophil function correlated with disease severity, consistent with the potential importance of suppressive neutrophil populations in sepsis. Reduced neutrophil and monocyte function correlated both with their own PD-L1 expression and with PD-1 expression on CD8+ T cells and NK cells. Conversely, reduced CD8+ T cell and NK cell functions (IFN-gamma production, granzyme B, and CD107a expression) correlated with elevated PD-L1+ LDNs. Importantly, addition of antibodies against PD-1 or PD-L1 restored function in neutrophil, monocyte, T cells, and NK cells, underlining the impact of the PD 1:PD-L1 axis in sepsis-immune suppression and the ability to treat multiple deficits with a single immunomodulatory agent. PMID- 27671249 TI - Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats. AB - In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30 ng/kg) before (Pre-SAH + VitD3) and after (Post-SAH + VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120 ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. Vitamin D3 significantly decreased brain edema and Evans blue extravasation. In addition, neurobehavioral scores were significantly higher in Pre-SAH + VitD3, but partly higher in Post-SAH + VitD3, group compared with SAH group. These protective effects of vitamin D3 were completely attenuated by intracerebroventricular injection of transcription inhibitor Actinomycin D and significantly inhibited by small interfering ribonucleic acid (siRNA) for vitamin D receptor and OPN in Pre-SAH + VitD3 rats. OPN expression was significantly higher in Pre-SAH + VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage. PMID- 27671251 TI - A new NAD+-dependent glyceraldehyde dehydrogenase obtained by rational design of l-lactaldehyde dehydrogenase from Escherichia coli. AB - NAD + -dependent glyceraldehyde dehydrogenases usually had lower activity in the nonphosphorylated Entner-Doudoroff (nED) pathway. In the present study, a new NAD + -dependent glyceraldehyde dehydrogenase was engineered from l-lactaldehyde dehydrogenase of E. coli (EC: 1.2.1.22). Through comparison of the sequence alignment and the active center model, we found that a residue N286 of l lactaldehyde dehydrogenase contributed an important structure role to substrate identification. By free energy calculation, three mutations (N286E, N286H, N286T) were chosen to investigate the change of substrate specificity of the enzyme. All mutants were able to oxidate glyceraldehyde. Especially, N286T showed the highest activity of 1.1U/mg, which was 5-fold higher than the reported NAD + -dependent glyceraldehyde dehydrogenases, and 70% activity was retained at 55 degrees C after an hour. Compared to l-lactaldehyde, N286T had a one-third lower Km value to glyceraldehyde. PMID- 27671252 TI - The System Is upon Me. AB - Although Spike Milligan is known to the public as a brilliant humorist, personal happiness and fulfilment seem to have eluded him. PMID- 27671253 TI - Hit the Timber-Let Yourself Go. AB - Dance has been with us since prehistoric times. Now the psychiatric profession is beginning to accept its potential as a means of treating mental disorder. PMID- 27671250 TI - Hyperglycemia is associated with more severe cytotoxic injury after stroke. AB - Hyperglycemia is a common complication after ischemic stroke, but its link to worse outcome is not well understood. We hypothesized that hyperglycemia may reflect an impaired metabolic response that is associated with worse cytotoxic brain injury. We performed retrospective analysis of magnetic resonance imaging from a cohort of acute ischemic stroke patients prospectively collected from 2006 to 2010 with baseline demographic and laboratory data as well as three-month outcomes. The severity of cytotoxic injury was quantified in vivo using apparent diffusion coefficient imaging by measuring the signal intensity within the stroke relative to the normal signal intensity of the contralateral hemisphere. Both hyperglycemia and lower apparent diffusion coefficient signal were associated with worse outcome after ischemic stroke (OR 0.239, p = 0.017; OR 1.11, p < 0.0001, respectively). Hyperglycemia was also associated with lower apparent diffusion coefficient (r = -0.32, p < 0.001). In multivariate analysis, apparent diffusion coefficient but not hyperglycemia was associated with outcome, suggesting that cytotoxicity may mediate the effect of hyperglycemia. For interventions designed to target hyperglycemia in acute ischemic stroke, a concomitant effect on the evolution of apparent diffusion coefficient may provide insight into whether hyperglycemia leads to or reflects worse cytotoxic injury. PMID- 27671254 TI - The Bliss of Madness. AB - Although mental illness often brings feelings of gloom and despair, sometimes a person classified as mentally ill feels supremely happy-the bliss of madness. PMID- 27671255 TI - Like Other People. AB - A new film, sponsored by the Mental Health Film Council, which pleads for the rights of the handicapped to enjoy emotional and sexual fulfilment in close personal relationships. PMID- 27671256 TI - A Right to Love? AB - Extracts from a report on public and professional attitudes towards the sexual and emotional needs of handicapped People. PMID- 27671257 TI - Nothing to Lose but Your Career Structure. AB - A growing number of students are casting aside the traditional view of work as a means of earning money, preferring to identify themselves more closely with a Particular community, where they can create their own life-style. PMID- 27671258 TI - Letters. PMID- 27671259 TI - Letters. PMID- 27671261 TI - News Review. PMID- 27671260 TI - Letters. PMID- 27671262 TI - Ennals Errant. PMID- 27671263 TI - A Willingness to Be Involved. AB - Young people living near Farleigh Hospital are coming to understand something of the problems facing large mental hospitals, through their own concern and involvement. PMID- 27671264 TI - From Where I Sit: Editorial Comment. PMID- 27671266 TI - The Rainbow Playgroup. AB - Photographs of a playgroup run by the Dagenham Association for Mental Health which caters for children at risk. PMID- 27671265 TI - A Fragile Line. AB - The brutal murders carried out by Charles Manson and his 'family' seemed bizarre and abnormal in the extreme. But was Manson so uniquely evil or did his environment just happen to provide opportunities where a philosophy of violence could flourish unchecked? PMID- 27671267 TI - Organised Chaos. AB - Learning to cope with the day-to-day tasks of life is a crucial factor in recovery from a depressive illness. A housewife explains how she has learnt to cope with the ups and downs by planning accordingly. PMID- 27671268 TI - Scan. AB - A personal view of the social services. PMID- 27671269 TI - Quantifying microstructural dynamics and electrochemical activity of graphite and silicon-graphite lithium ion battery anodes. AB - Despite numerous studies presenting advances in tomographic imaging and analysis of lithium ion batteries, graphite-based anodes have received little attention. Weak X-ray attenuation of graphite and, as a result, poor contrast between graphite and the other carbon-based components in an electrode pore space renders data analysis challenging. Here we demonstrate operando tomography of weakly attenuating electrodes during electrochemical (de)lithiation. We use propagation based phase contrast tomography to facilitate the differentiation between weakly attenuating materials and apply digital volume correlation to capture the dynamics of the electrodes during operation. After validating that we can quantify the local electrochemical activity and microstructural changes throughout graphite electrodes, we apply our technique to graphite-silicon composite electrodes. We show that microstructural changes that occur during (de)lithiation of a pure graphite electrode are of the same order of magnitude as spatial inhomogeneities within it, while strain in composite electrodes is locally pronounced and introduces significant microstructural changes. PMID- 27671270 TI - Illuminating Coronary Artery Involvement in Takayasu Arteritis. PMID- 27671271 TI - Reduced graphene oxide enwrapped phosphors for long-term thermally stable phosphor converted white light emitting diodes. AB - The long-term instability of the presently available best commercial phosphor converted light-emitting diodes (pcLEDs) is the most serious obstacle for the realization of low-cost and energy-saving lighting applications. Emission from pcLEDs starts to degrade after approximately 200 h of operation because of thermal degradation of the phosphors. We propose a new strategy to overcome this thermal degradation problem of phosphors by wrapping the phosphor particles with reduced graphene oxide (rGO). Through the rGO wrapping, we have succeeded in controlling the thermal degradation of phosphors and improving the stability of fabricated pcLEDs. We have fabricated pcLEDs with long-term stability that maintain nearly 98% of their initial luminescence emission intensity even after 800 h of continuous operation at 85 degrees C and 85% relative humidity. The pcLEDs fabricated using SrBaSi2O2N2:Eu2+ phosphor particles wrapped with reduced graphene oxide are thermally stable because of enhanced heat dissipation that prevents the ionization of Eu2+ to Eu3+. We believe that this technique can be applied to other rare-earth doped phosphors for the realization of highly efficient and stable white LEDs. PMID- 27671272 TI - Impact of a Computerized Antithrombotic Risk Assessment Tool on the Prescription of Thromboprophylaxis in Atrial Fibrillation: Hospital Setting. AB - The computerized antithrombotic risk assessment tool (CARAT) is an online decision-support algorithm that facilitates a systematic review of a patient's stroke risk, bleeding risk, and pertinent medication safety considerations, to generate an individualized treatment recommendation. The CARAT was prospectively applied across 2 hospitals in the greater Sydney area. Its impact on antithrombotics utilization for thromboprophylaxis in patients with nonvalvular atrial fibrillation was evaluated. Factors influencing prescribers' treatment selection were identified. The CARAT recommended a change in baseline therapy for 51.8% of patients. Among anticoagulant-eligible patients (ie, where the risk of stroke outweighed the risk of bleeding) using "nil therapy" or antiplatelet therapy at baseline, the CARAT recommended an upgrade to warfarin in 60 (30.8%) patients. For those in whom the bleeding risk outweighed the stroke risk, the CARAT recommended a downgrade from warfarin to safer alternatives (eg, aspirin) in 37 (19%) patients. Among the "most eligible" (ie, high stroke risk, low bleeding risk, no contraindications; n = 75), the CARAT recommended warfarin for all cases. Discharge therapy observed a marginal increase in anticoagulation prescription in eligible patients (n = 116; 57.8% vs 64.7%, P = .35) compared to baseline. Predictors of warfarin use (vs antiplatelets) included congestive cardiac failure, diabetes mellitus, and polypharmacy. The CARAT was able to optimize the selection of therapy, increasing anticoagulant use among eligible patients. With the increasing complexity of decision-making, such tools may be useful adjuncts in therapy selection in atrial fibrillation. Future studies should explore the utility of such tools in selecting therapies from within an expanded treatment armamentarium comprising the non-vitamin K antagonist oral anticoagulants. PMID- 27671273 TI - Community pharmacist's responsibilities with regards to traditional medicine/complementary medicine products: A systematic literature review. AB - BACKGROUND: The use of Traditional Medicine/Complementary Medicine (TM/CM) products has gained popularity in many countries. There is a growing body of evidence to support that concomitant use of TM/CM products with certain pharmaceutical medicines may adversely affect treatment outcomes. There is a general consensus that pharmacists have a role to play in the safe and appropriate use of these products. However, the extent of their involvement and responsibilities are not yet defined. Clear guidelines that inform their duty of care are essential for pharmacists to establish their role in the management of TM/CM product use. OBJECTIVES: The purpose of this study was to determine pharmacist's responsibilities with regards to TM/CM products that have been discussed in the literature since 2000. METHODS: A literature search in 3 electronic databases (Web of Science, Science Direct and PubMed) was used to extract publications from 2000 to 2015 that related pharmacist to TM/CM products. Out of the 2859 publications extracted for abstract review, 171 documents were selected for full text assessment. 41 publications which reported findings from exploratory studies or discussed pharmacists' responsibilities towards TM/CM products were selected for inclusion in this study. RESULTS: Seven major responsibilities were frequently discussed in the literature: (1) to acknowledge the use; (2) to be knowledgeable about the TM/CM products; (3) to ensure safe use of TM/CM products; (4) to document the use of TM/CM products; (5) to report ADRs related to TM/CM products; (6) to educate about TM/CM products; and (7) to collaborate with other health care professionals. CONCLUSION: Various forms and levels of pharmacists' responsibilities with TM/CM products have been mentioned in the literature. Subsequent work towards a common consensus must take into account three influential factors strategically: the scope of TM/CM products, objectives of pharmacists' involvement and the perspectives of key stakeholders. PMID- 27671274 TI - Minimal-invasive TLIF. PMID- 27671276 TI - Cervical total disc replacement (TDR). PMID- 27671275 TI - MIS revision of de novo scoliosis and stenosis, following open spinal instrumentation. PMID- 27671277 TI - Surgical management of thoracic disc herniation. PMID- 27671278 TI - Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation. AB - PURPOSE: Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. METHODS: A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. RESULTS: Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. CONCLUSIONS: Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment. PMID- 27671280 TI - In vitro analysis of circumferential joint replacement, including bilateral facet joint replacement with lateral lumber disc prosthesis: a parametric investigation of disc sizing. AB - PURPOSE: Lateral lumbar disc prosthesis (LLDP) is an innovative device used to restore motion in select patients through a lateral retroperitoneal approach. No in vitro biomechanical studies have been published. Further, the potential for in toto circumferential joint restoration when use of this anterior disc is combined with facet replacement remains unqualified but signifies a potentially interesting clinical direction. METHODS: Researchers conducted a biomechanical feasibility study of an LLDP designed to investigate parameters of disc sizing used with bilateral facet joint replacement in a cadaveric model. Tested constructs at L4-L5 included (1) intact, (2) LLDP, (3) LLDP + wide discectomy, (4) LLDP + bilateral facetectomy, and (5) LLDP + bilateral facet joint replacement (BFJR). Investigators tested instrumented constructs (2-5) with an LLDP at compact-fit and lax-fit heights and used raw data to perform statistical analysis by repeated measures analysis of variance (ANOVA), along with Student Newman-Keuls post hoc analysis (p <= 0.05). RESULTS: Increased height of the LLDP resulted in significantly less motion compared with intact. Widening the discectomy while using lax-fit sizing led to motion similar to intact in flexion extension. As expected, motion was greater with lax-fit height than with compact fit height in all loading modes and constructs, as is noted with a widened discectomy. The L4-L5 center of rotation was maintained regardless of placement of the LLDP. CONCLUSIONS: After bilateral facetectomy, reconstruction of the three-joint complex achieved by combining the LLDP with BFJR may provide a viable alternative to current clinical treatment regimens. PMID- 27671279 TI - Efficacy of antifibrinolytic agents on surgical bleeding and transfusion requirements in spine surgery: a meta-analysis. AB - PURPOSE: Spine surgery is usually associated with large amount of blood loss and blood transfusion. Excessive blood loss may cause hypotension, inadequate oxygenation of organs, necessitate allogeneic blood transfusion, and spinal epidural hematoma formation. Aprotinin, TXA, and EACA are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The purpose of this study was to assess the efficacy of using antifibrinolytic agents in reducing blood loss and blood transfusions in spine surgery. METHODS: PubMed, Embase, and Cochrane-controlled trials register were used to identify RCTs published before April 2015 that examined the effectiveness of intravenous aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) on reduction of blood loss and blood transfusions, compared with placebo in spine surgery. Randomized controlled trials reported the primary outcome that included total blood loss, intra-operative blood loss, post-operative blood loss, blood transfusion requirements, blood transfusion rate, and incidence of deep vein thrombosis. Meta-analysis was performed using the Stata12.0. Weighted mean difference with 95 % confidence intervals was used to summarize the findings across the trials for continuous outcomes. Dichotomous data were expressed as risk ratios with 95 % confidence intervals. A P < 0.05 was considered statistically significant. RESULTS: 17 studies involving 1191 patients were identified. Among them, 13 RCTs with 943 patients were included for the evaluation of total blood loss. Compared with the control group, the antifibrinolytic agents reduced total blood loss (SMD = -0.62; 95 % CI -0.75, 0.48; P = 0.000), The aprotinin group (SMD = -0.80; 95 % CI -1.22, -0.37; P = 0.938), The TXA group (SMD = -0.75; 95 % CI -0.93, -0.57; P = 0.000), and the EACA group (SMD = -0.28; 95 % CI -0.54, -0.01; P = 0.185). Thirteen RCTs with eight hundred and ninety four patients were included for the evaluation of intra operative blood loss. Compared with the control group, the antifibrinolytic agents reduced intra-operative blood loss (SMD = -0.41; 95 % CI -0.55, -0.28; P = 0.010), The aprotinin group (SMD = -0.62; 95 % CI -0.93, -0.30; P = 0.862), The TXA group (SMD = -0.47; 95 % CI -0.64, -0.29; P = 0.005), and the EACA group (SMD = -0.16; 95 % CI -0.42, -0.11; P = 0.897). Eight RCTs with six hundred and seven patients were included for the evaluation of post-operative blood loss. Compared with the control group, the antifibrinolytic agents reduced post-operative blood loss (SMD = -0.68; 95 % CI -0.85, -0.51; P = 0.000), the aprotinin group (SMD = 0.48; 95 % CI -0.85, -0.12; P = 0.036), the TXA group (SMD = -0.80; 95 % CI 1.01, -0.59; P = 0.000), and the EACA group (SMD = -0.32; 95 % CI -0.68, -0.04; P = 0.009). Ten RCTs with seven hundred and twenty twopatients were included for the evaluation of blood transfusion. Compared with the control group, the antifibrinolytic agents reduced blood transfusion (SMD = -0.68; 95 % CI -0.85, 0.51; P = 0.000), the aprotinin group (SMD = -0.80; 95 % CI -1.22, -0.37; P = 0.938), the TXA group (SMD = -0.38; 95 % CI -0.58, -0.18; P = 0.000), and the EACA group (SMD = -0.28; 95 % CI -0.54, -0.01; P = 0.185). Twelve RCTs with eight hundred and fifteenpatients were included for the evaluation of blood transfusion rate. The transfusion rate was 35.6 % in the patients with antifibrinolytic agents and 55.2 % in the patients with placebo (RR = 0.75; 95 % CI 0.63, 0.89; P = 0.939). All studies were included for the evaluation of safety, with a total of eight thromboembolic events reported overall (two in the experimental group and six in the control group). CONCLUSIONS: The antifibrinolytic agents were able to reduce perioperative blood loss and transfusion requirements in spine surgery. TXA appeared more effective than aprotinin and EACA in reducing total blood loss, intra-operative blood loss, and blood transfusion according to the results of this analysis. The three groups in reducing the post-operative blood loss are significantly better than control groups. There was no evidence that the use of antifibrinolytic agents was a risk factor for thromboembolism in spine surgery. Further multicenter, large-sample, double-blind RCTs are required to confirm the efficacy and safety of the three antifibrinolytic agents in spine surgery. PMID- 27671281 TI - Normative spino-pelvic parameters in patients with the lumbarization of S1 compared to a normal asymptomatic population. AB - INTRODUCTION: Normal spino-pelvic values for patients with lumbarization of S1 have not been described in the literature. Presented are the normal values for this population group, the prevalence of S1 lumbarization, and the correlation between pelvic incidence (PI) and lumbar lordosis (LL) in this group. METHODS: Two databases of asymptomatic patients were combined to identify 11 patients with the lumbarization of S1. The whole spine images were used to measure the true prevalence rate. Lumbar 3D EOS models were built to measure spino-pelvic parameters for the lumbarization group compared to the asymptomatic population. Seven patients appeared at first to have six lumbar vertebrae, but counting caudally from C2 showed this was not the case. RESULTS: 11/268 patients demonstrated the lumbarization of S1 to give a true prevalence rate of 4.1 %. The lumbarization group demonstrated a statistically significant difference with regard to PI, PT, and SS, and total lordosis measured from superior endplate of L1 to the superior endplate of the first fixed sacral segment. L6I was not significantly correlated to lordosis; however, PI did have a significant correlation with lordosis. Lordosis could be estimated in this group by the equation: [Formula: see text]. CONCLUSION: Incomplete imaging of the spine may lead to false estimation of the prevalence of lumbarization. Patients with lumbarization have higher lordosis values and lordosis can now be estimated during pre-operative planning for this group. PMID- 27671282 TI - Optimal area of lateral mass mini-screws implanted in plated cervical laminoplasty: a radiography anatomy study. AB - PURPOSE: Lateral mass mini-screws used in plated cervical laminoplasty might penetrate into facet joints. The objective is to observe this complication incidence and to identify the optimal areas for 5- and 7-mm-long mini-screws to implant on lateral mass. METHODS: 47 patients who underwent plated cervical laminoplasty were included. The optimal area for mini-screws implanting was set according to pre-operative 3D CT reconstruction data. Then, each posterior lateral mass surface was divided into three regions: 7-mm region, 5-mm region, and dangerous area. The mini-screw implanted region was recorded. Post-operative CT images were used to identify whether the mini-screws penetrated into facet joints. RESULTS: 235 mini-plates and 470 lateral mass mini-screws were used in the study. 117 (24.9%) mini-screws penetrated 88 (37.4%) facet joints. The 5-mm long mini-screw optimal area occupied the upper 72, 65, 65, 64, and 65 % area of the posterior-lateral mass surface for C3-7, while the 7-mm-long mini-screw optimal area encompassed the upper 54, 39, 40, 33, and 32 %. Only 7-mm-long mini screws were used to fix the plate to the lateral mass. 4 of 240 mini-screws in 7 mm region, 67 of the 179 mini-screws in 5-mm region, and 46 of the 51 mini-screws in dangerous region penetrated into the facet joint. The differences in the rate of facet joint penetration related to region were statistically significant (P < 0.001). CONCLUSIONS: The facet joint destruction by mini-screws was not a rare complication in plated cervical laminoplasty. The optimal areas we proposed may help guide the mini-screw implantation positions. PMID- 27671283 TI - Bacterial toxin's DNA vaccine serves as a strategy for the treatment of cancer, infectious and autoimmune diseases. AB - DNA vaccination -a third generation vaccine-is a modern approach to stimulate humoral and cellular responses against different diseases such as infectious diseases, cancer and autoimmunity. These vaccines are composed of a gene that encodes sequences of a desired protein under control of a proper (eukaryotic or viral) promoter. Immune response following DNA vaccination is influenced by the route and the dose of injection. In addition, antigen presentation following DNA administration has three different mechanisms including antigen presentation by transfected myocytes, transfection of professional antigen presenting cells (APCs) and cross priming. Recently, it has been shown that bacterial toxins and their components can stimulate and enhance immune responses in experimental models. A study demonstrated that DNA fusion vaccine encoding the first domain (DOM) of the Fragment C (FrC) of tetanus neurotoxin (CTN) coupled with tumor antigen sequences is highly immunogenic against colon carcinoma. DNA toxin vaccines against infectious and autoimmune diseases are less studied until now. All in all, this novel approach has shown encouraging results in animal models, but it has to go through adequate clinical trials to ensure its effectiveness in human. However, it has been proven that these vaccines are safe, multifaceted and simple and can be used widely in organisms which may be of advantage to public health in the near future. This paper outlines the mechanism of the action of DNA vaccines and their possible application for targeting infectious diseases, cancer and autoimmunity. PMID- 27671284 TI - Pyocyanin as anti-tyrosinase and anti tinea corporis: A novel treatment study. AB - OBJECTIVE: The aim of this study was to evaluate the efficiency of pyocyanin pigment as a novel compound active against tyrosinase with its depigmentation efficiency for combating Trichophyton rubrum which could be a major causative agent of tinea corporis. METHODS: Fifty swabs of fungal tinea corporis infections were collected and identified. Five MDRPA isolates were tested for their levels of pyocyanin production. The purified extracted pyocyanin was characterized by UV spectrum and FT-IR analysis. Pyocyanin activity against tyrosinase was determined by dopachrome micro-plate. In addition, the antidermatophytic activity of pyocyanin against T. rubrum was detected by radial growth technique. In vivo novel trial was conducted to evaluate the efficiency and safety of pyocyanin as an alternative natural therapeutic compound against T. rubrum causing tinea corporis. RESULTS: Purified pyocyanin showed highly significant inhibitory activity against tyrosinase and T. rubrum. In vivo topical treatments with pyocyanin ointment revealed the efficiency of pyocyanin (MIC 2000 MUg/ml) to cure tinea corporis compared to fluconazole, which showed a partial curing at a higher concentration (MIC 3500 MUg/ml) after two weeks of treatment. In addition, the results revealed complete healing and disappear of hyperpigmentation by testing the safety of pyocyanin ointment and its histopathological efficiency in the skin treatment without any significant toxic effect. CONCLUSION: Pyocyanin pigment could be a promising anti-tyrosinase and a new active compound against T. rubrum, which could be a major causative agent of tinea corporis. In fact, if pyocyanin secondary metabolite is going to be used in practical medication, it will support the continuous demand of novel antimycotic natural agents against troublesome fungal infections. PMID- 27671285 TI - Estimation of anterior glenoid bone loss area using the ratio of bone defect length to the distance from posterior glenoid rim to the centre of the glenoid. AB - PURPOSE: Estimation of anterior glenoid bone loss is important for surgical decision-making. The purpose of this study was to describe a method for estimating anterior glenoid bone loss. METHODS: Thirty-nine cadaveric glenoids were digitized to obtain glenoid geometry. Glenoid bare spot centre, arthroscopic centre, and centre of the inferior glenoid circle relative to the geometric centre were measured. To simulate anterior glenoid bone loss, imaginary sequential osteotomies were created 0 degrees , 22.5 degrees , and 45 degrees to the superior-inferior line in a 3D digitizing programme. Per cent of anterior glenoid bone loss area was calculated as the percentage of defect area relative to the entire area of the glenoid. The relationship between area loss and ratio of bone defect length to the distance from posterior glenoid to various centres was determined. RESULTS: As the ratio of bone defect length to the distance from posterior glenoid to all three centres increased, the per cent area of bone loss increased exponentially. The ratio using the inferior circle centre and arthroscopic centre was highly correlated to the actual glenoid bone loss in all osteotomies (R 2 > 0.90). The ratio using the centre of bare area had the lowest correlation. The ratio of defect length to distance from posterior glenoid to arthroscopic centre greater than 2.4 for 0 degrees and 2.0 for 45 degrees osteotomies results in bone loss area greater than 25 %. The bare area centre had the largest variation. Average bone loss was overestimated when the centre of bare spot was used compared to other centre locations. CONCLUSION: Per cent of anterior glenoid bone loss can be estimated using the ratio of bone defect length to the distance from posterior glenoid rim to the centre of inferior glenoid circle or arthroscopic centre either preoperatively using 3D CT or arthroscopically which can be useful for determining surgical treatment. PMID- 27671288 TI - We must go for gold in public health. PMID- 27671289 TI - Exploring the premise of lost altruism: content analysis of two codes of ethics. AB - As an ideal, altruism has long enjoyed privileged status in medicine and medical education. As a practice, altruism is perceived to be in decline in the current generation. A number of educational efforts are underway to reclaim this "lost value" of medicine. In this paper we explore constructions of altruism over a defined period of time through a content analysis of the Canadian and Australian Medical Associations (CMA and AMA respectively) Codes of Ethics. We analyzed all editions of both Codes (1868-2004), using a content analysis approach, including thematic analysis. We coded as altruistic or non-altruistic, respectively, statements in which the interest of the patient is placed ahead of the physician's and statements in which the interest of the physician is given primacy. We examined the pattern of appearance and disappearance of these statements over time. We identified 13 altruistic and 2 non-altruistic statements across all editions. There is a gradual and uneven loss of altruistic content over time. The CMA Codes of 1938, 1970 and 2004 and the AMA code of 1992 represent significant change points. The most recent versions of both Codes contain only 1 altruistic statement and both non-altruistic statements. We conclude that altruism appears to be a fluid and changing concept over time. Loss of altruism is not merely a current generational issue but extends through the past century and is likely due to political and social forces. These results call into question current educational attempts to reclaim altruism, and point to the social evolution of the ideal. PMID- 27671287 TI - Evaluating the impact of two training interventions to improve diagnosis and case management of malaria and pneumonia in Uganda. AB - We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2.4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16.0% across all age groups. IMID decreases pneumonia prevalence by more than 3.0% across all age groups while IMID + OSS decreases it by more than 1.0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7.8% by IMID across all age groups and IMID + OSS decreases this number by 30.5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0.52% at baseline, and IMID and IMID + OSS reduce it by 6.6% and 23.6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14-91% in reduction of disease cases. PMID- 27671286 TI - Popliteus impingement after TKA may occur with well-sized prostheses. AB - PURPOSE: To determine the mechanisms and extents of popliteus impingements before and after TKA and to investigate the influence of implant sizing. The hypotheses were that (1) popliteus impingements after TKA may occur at both the tibia and the femur, and (2) even with an apparently well-sized prosthesis, popliteal tracking during knee flexion is modified compared to the preoperative situation. METHODS: The location of the popliteus in three cadaver knees was measured using computed tomography, before and after implantation of plastic TKA replicas, by injecting the tendon with radiopaque liquid. The pre- and post-operative positions of the popliteus were compared from full extension to deep flexion using normosized, oversized, and undersized implants (one size increments). RESULTS: At the tibia, TKA caused the popliteus to translate posteriorly, mostly in full extension: 4.1 +/- 2 mm for normosized implants, and 15.8 +/- 3 mm with oversized implants, but no translations were observed when using undersized implants. At the femur, TKA caused the popliteus to translate laterally at deeper flexion angles, peaking between 80 degrees and 120 degrees : 2 +/- 0.4 mm for normosized implants and 2.6 +/- 0.5 mm with oversized implants. Three-dimensional analysis revealed prosthetic overhang at the posterosuperior corner of normosized and oversized femoral components (respectively, up to 2.9 mm and 6.6 mm). CONCLUSIONS: A well-sized tibial component modifies popliteal tracking, while an undersized tibial component maintains more physiologic patterns. Oversizing shifts the popliteus considerably throughout the full arc of motion. This study suggests that both femoro- and tibio-popliteus impingements could play a role in residual pain and stiffness after TKA. PMID- 27671290 TI - Association of luteal blood flow with follicular size, serum estrogen and progesterone concentrations, and the inducibility of luteolysis by PGF2alpha in dairy cows. AB - The aim of this study was to investigate the compatibility of the visual evaluation result of the blood flow characteristics and the blood flow measurements of the CL and the predictability of the responses given by corpora lutea with varying levels of blood flow to an induction of luteolysis by a PGF2alpha injection and to determine the possibility of increase in serum estrogen and progesterone concentrations in parallel with increased luteal blood flow (LBF). The cows, bearing a CL (n = 60; postpartum 35 days), were injected with PGF2alpha and were monitored for signs of estrous following the first injection. The cows, which did not show estrous signs, were examined for the presence of a CL on Day 14, whereas those that showed signs of estrous were examined on Day 10 following the onset of estrous. The level of LBF was visually graded as + (low; GI), ++ (medium; GII), +++ (high; GIII), and ++++ (very high; GIV). Immediately after the examination of LBFs, a second intramuscular injection of PGF2alpha was injected. In the cows, which were determined to be in estrous, the diameter of the Graafian follicles was measured by B-mode ultrasonography. Subsequently, these animals were artificially inseminated. The animals, which did not show estrous after the second injection, were examined as previously described and monitored for signs of estrous. A strong correlation (r = 0.654; P < 0.001) was determined to exist between the results of the visual examination of the images and the results obtained for the LBF area with the use of the Pixel Flux software. GIII (0.83 +/- 0.15 cm2) and GIV (1.03 +/- 0.48 cm2) were found to differ from GI (0.47 +/- 0.23 cm2) and GII (0.51 +/- 0.12 cm2) for the size of the LBF (P < 0.001). Serum progesterone levels in groups (GI, GII, GIII, and GIV) were determined to be 4.44 +/- 2.42 ng/mL, 6.03 +/- 2.37 ng/mL, 7.01 +/- 2.94 ng/mL, and 7.17 +/- 1.69 ng/mL, respectively. The comparative evaluation of the study groups showed that the groups did not statistically differ for the period between PGF2alpha injection and the onset of estrous, mean Graafian follicle size and estrogen levels. No direct correlation existed between these reproductive parameters and LBF. PMID- 27671291 TI - Searching biomarkers for mental disorders-lessons from Alzheimer's disease. PMID- 27671292 TI - Bacterial and Archaeal Diversities in Maotai Section of the Chishui River, China. AB - The Chishui River is the last undammed tributary of the upper Yangtze River, extends cross Sichuan, Yunnan and Guizhou provinces, and it is the significant water source of Maotai liquor, Southwest of China. We investigated microbial community of the Chishui River in the Maotai town section, because of deep relationship between the water and the most famous Chinese liquor, Maotai liquor. In this study, diversities of bacteria and archaea of four seasons were analyzed in two different sampling sites using a barcoded 16S rRNA gene-pyrosequencing approach. The results show that the predominant community among all bacteria is Proteobacteria (70.16-94.29 %), of which Gamma-proteobacteria made up the largest portion. Bacterial community structure in spring and autumn tended to group together, and the operational taxonomic units of bacteria peaked in summer. The quantitative PCR (q-PCR) results revealed significantly higher number of gene copies in the downstream than that in the upstream, and were slightly higher in summer and spring than other seasons. Archaeal community structures had no obvious regular pattern, and species richness was higher in downstream in all seasons. Euryarchaeota and Thaumarchaeota were the dominant groups in archaeal populations, and abundant ammonia-oxidizing archaea was detected. The study significantly improved our understanding of microbial community in Maotai section of the Chishui River, where the unique and world-famous Maotai liquor is produced. PMID- 27671294 TI - Synthesis of Arylpiperazine Derivatives as Protease Activated Receptor 1 Antagonists and Their Evaluation as Antiproliferative Agents. AB - BACKGROUND: Protease activated receptor-1 (PAR1) is a G-coupled receptor activated by alpha-thrombin and other proteases. Several reports have demonstrated the PAR1 involvement in tumorigenesis and tumor progression. In order to investigate on potential use of PAR1 antagonists as antiproliferative agents. AIMS: We have identified a series of arylpiperazine derivatives acting as PAR1 antagonists; the selected molecules have been evaluated for their antiproliferative properties. METHOD: All the compounds inhibited the growth of a panel of cell lines expressing PAR1; two of them, compounds 13 and 15, were able to inhibit, in a dose dependent manner, the growth of the selected cell lines with the lowest IC50 values, and were further characterized to define the mechanism responsible for the observed antiproliferative effect. RESULT: This study directed us to the identification of two interesting leads that may help to further validate PAR1 as an important therapeutic target for cancer treatment. PMID- 27671295 TI - Design and Synthesis of NO-releasing Betulinic Acid Derivatives as Potential Anticancer Agents. AB - A total of 16 targeted NO-releasing betulinic acid (BA) derivatives were designed and synthesized as potential anticancer agents. Most IC50 values were under 1.0 MUM in vitro test against HepG2 and B16. The result suggested that derivatives of BA with alpha,beta-unsaturated ketone skeleton possessed significant cytotoxic activities than the others, among which derivatives with three carbons in diol linker (15b and 15c) exhibited the highest anti-cancer activity. NO-releasing amount detection of partial target compounds suggested that NO-releasing amount of this series of BA derivatives positively correlates with their cytotoxic activities. The anti-angiogenic activity of partial target compounds on zebrafish embryos in our experiment did not show any effects on the SIVs, however, they exhibited different influence on ISVs, with only 15a and 15d better than the negative control. PMID- 27671296 TI - Targeted Therapy Towards Cancer-A Perspective. AB - Radionuclide antibody conjugates (RACs) and antibody-drug conjugates (ADCs) can function as biotherapeutic missiles in order to target cancer cells and destroy them. The advent of new technology platforms consisting of imaging modalities, drug design and radiochemistry will facilitate the personalised approach for cancer patient treatment programmes. The utilisation of radionuclides and cytotoxic drugs conjugated to biovectors can deliver a cytotoxic drug payload with the ability to emit alpha and/or beta particles in the vicinity of the tumour by binding onto the cancer cells surface antigens initiating cell death. This perspective aims to provide an insight into targeted therapies in the treatment of various cancerous disease states including breast cancer, prostate bone metastases, lymphoma and leukaemia. PMID- 27671297 TI - Discovery of Potent Bruton's Tyrosine Kinase Inhibitors Using Ligand Based Modeling. AB - BACKGROUND: Bruton's Tyrosine Kinase (BTK) is a one of the Tec tyrosine kinase family. It has an essential role in B-cell development and function. Activation of BTK has been associated with the pathogenesis of many types of lymphomas and leukemia, and involved in non-life threatening autoimmune diseases. OBJECTIVE: In this study, exhaustive pharmacophore modeling was combined with QSAR analyses to examine the structural requirements for anti-BTK activities. METHOD: Genetic function algorithm (GFA) was coupled with multiple linear regression (MLR) analysis to select the best combinations of physicochemical descriptors and pharmacophoric hypothesis capable of generating predictive and self-consistent QSAR models. The optimum pharmacophores were decorated with exclusion volumes to improve their receiver operating characteristic (ROC) curve properties. The best predictive QSAR model and its corresponding pharmacophore models were validated by discovering of novel promising BTK inhibitors retrieved from the National Cancer Institute (NCI) database. RESULTS: Several potent hits exhibited anti proliferative activities on U-937 cell-line in low micromolar IC50, and one active compound showed nontoxic activities on normal fibroblast cell line. CONCLUSION: Our efforts culminated in the identification of potent BTK ligands having desired inhibitory activities and structurally distinct from known active reference compounds (i.e., training compounds) and represent new chemotypes. PMID- 27671299 TI - 4-Methylumbelliferones Analogues as Anticancer Agents: Synthesis and in Cell Pharmacological Studies. AB - BACKGROUND: Cancer is one of the most serious clinical problems worldwide, and considerable efforts have been devoted to discovering therapeutic agents with novel modes of action. Natural and synthetic coumarin derivatives have attracted intense research interest due to their diverse structural features and remarkable array of biological properties. OBJECTIVE: In the present study, we synthesized a series of 4-MU derivatives containing urea-piperazine and thioureapiperazine moieties and evaluated their antitumor activities to find efficacy antitumor drugs. METHOD: Cell proliferation, apoptosis, cell cycle, the generation of reactive oxygen species and calcium were measured using MTT assay and flow cytometry, respectively. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The effect of 4l on apoptosis related mRNA expression in NCI-H460 cells was detected by RT-PCR. RESULTS: Most of the target compounds exhibited potential anticancer activities against tested cancer cells but had low cytotoxicity to normal cells. Compound 4l inhibited the growth and proliferation of NCI-H460 cells and resulted in apoptosis. Successive studies conducted with 4l in NCI-H460 cells demonstrated that this compound induced the intracellular reactive oxygen species generation and calcium overload, suppressed nuclear factor-kappaB (NF-kappaB) activity and regulated anti- and pro-apoptotic proteins. In addition, compound 4l effectively arrested NCI-H460 cells in G2 phase and altered the cell cycle regulatory proteins especially cyclin B1. CONCLUSION: Compound 4l exerts significant anticancer effects on NCI-H460 cells in vitro through targeting of mitochondria-dependent apoptotic pathway. These results indicate that the strategy for rational design of 4-MU derivatives may identify potential anticancer agents. PMID- 27671298 TI - Colorectal, Prostate and Pancreas Human Cancers Targeted Bioassay-guided Isolations and Characterization of Chemical Constituents from Tephrosia apollinea. AB - BACKGROUND: Cancer is characterized by uncontrolled cell division caused by dysregulation of cell proliferation. Therefore, agents that impair cancer cell proliferation could have potential therapeutic value. Higher plants are considered to be a good source of anticancer agents, and several clinically tested chemotherapeutic agents have been isolated from plants or derived from constituents of plant origin. METHODS: In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast). RESULTS: Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 MUg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells. CONCLUSION: Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies. PMID- 27671300 TI - Synthetic Mono/di-halogenated Coumarin Derivatives and Their Anticancer Properties. AB - BACKGROUND: Coumarins are naturally occurring plant metabolites and several synthetic coumarin analogues are known for their various pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti inflammatory and antiviral properties. Objective; Keeping this promising pharmacological properties in mind, in the present investigation, mono/dihalogenated coumarin analogues CMRN1-CMRN7 have been synthesized and evaluated for their anticancer activity. METHOD: The cytotoxicity potential of the test compounds was evaluated against UACC-62, MCF-7 and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay. The apoptotic potential of the coumarin compounds was evaluated against UACC-62 cell by assessing membrane change, mitochondria membrane potential, pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. RESULTS: The test compounds CMRN1, CMRN2, CMRN4 and CMRN5 have strongly suppressed the cell proliferation of UACC-62 and MCF-7 cancer cell lines. Furthermore the test compounds CMRN1, CMRN2, CMRN4 and CMRN5 exerted antiproliferative effects through apoptosis induction against UACC-62. CONCLUSION: Compounds CMRN1, CMRN2, CMRN4 and CMRN5 can be considered as lead compounds to arrive at a promising anticancer agents. PMID- 27671302 TI - Thiosemicarbazone Derivative Induces in vitro Apoptosis in Metastatic PC-3 Cells via Activation of Mitochondrial Pathway. AB - BACKGROUND: Thiosemicarbazone (TSC) is a Schiff base that has been receiving considerable attention owing to its promising biological implication and remarkable pharmacological properties. The most promising drug candidate of this class would be Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) which has entered phase II clinical trials as a potent anti-cancer chemotherapeutic agent. OBJECTIVE: The current research aimed to synthesize several Schiff base ligands from (3-formyl-4-hydroxyphenyl) methyltriphenylphosphonium (T). Additionally, the current research aimed to study the growth inhibitory effect of triphenylphosphonium containing thiosemicarbazone derivatives on PC-3 cells by deciphering the mechanisms involved in cell death. METHOD: The compounds were characterized by various spectroscopic methods (infrared spectra, 1H NMR, 13C NMR, HRESIMS and X-ray crystallography) and the results were in conformity with the structure of the targeted compounds. Growth inhibitory effect of the compounds were performed against six human cell lines. RESULTS: DM(tsc)T displayed most potent activity against PC-3 cells with IC50 value of 2.64 +/- 0.33 MUM, surpassing that of the positive control cisplatin (5.47 +/- 0.06 MUM). There were marked morphological changes observed in DM(tsc)T treated cells stained with acridine orange and ethidium bromide which were indicative of cell apoptosis. Treatment with DM(tsc)T showed that the cell cycle is arrested in the G0/G1 phase after 72 hours. Mitochondrial membrane potential loss was observed in cells treated with DM(tsc)T, indicating the apoptosis could be due to mitochondria mediated pathway. CONCLUSION: This study indicates that DM(tsc)T would serve as a lead scaffold for rational anticancer agent development. PMID- 27671301 TI - Polo-like Kinase 1-targeting Chitosan Nanoparticles Suppress the Progression of Hepatocellular Carcinoma. AB - BACKGROUND: Recent investigations have implicated that Chitosan-nucleotide nanoparticles might be useful non-viral carriers in gene therapy. Polo-like kinase 1 (PLK1) has been reported to be an important oncogene that exerted considerable therapeutic merit in hepatocellular carcinoma (HCC). OBJECTIVE: We explored whether Galactosylated chitosan-graft-poly(ethylene glycol) (GCP) nanoparticlemediated delivery of PLK1 siRNA nucleotides could serve as an effective anti-cancer agent for HCC therapy. METHOD: GCP nanoparticles were prepared to deliver PLK1 siRNA oligos into HCC cells and tissues. Real-time fluorescence quantitative PCR (RFQ-PCR) and western blotting analyses were used to examine the efficiency of nanoparticle-mediated depletion of PLK1 in HepG2 cells. Cell proliferation and apoptotic death were also examined using flow cytometric, MTT and TUNEL assays. Xenograft mouse model was conducted to assess the impact of GCP/siRNA nanoparticles on the in vivo growth of HCC cells. RESULTS: GCP nanoparticles bind to PLK1 siRNA efficiently. The particle size and zeta potential of GCP/siRNA nanoparticles are suitable for cellular delivery. PLK1-targeting nanoparticles inhibited cell proliferation through inducing G2/M phase arrest with a higher efficacy than a selective and potent PLK1 inhibitor BI 2536. Moreover, TUNEL assay revealed that PLK1-siRNA nanoparticles induced apparent apoptosis in HepG2 cells. In addition, PLK1-targeting nanoparticles induced significant upregulation of cellular p53, Bax and p21, whereas the level of Bcl-2 was impaired in HCC cells. Moreover, PLK1-targeting nanoparticles impaired the tumorigenicity of HepG2 cells in vivo. CONCLUSION: These findings indicate that PLK1-targeting nanoparticles exert considerable therapeutic merit and GCP/siRNA nanoparticles would be a valuable therapeutic carrier for HCC. PMID- 27671303 TI - TGF-beta Signal Transduction in Pancreatic Carcinoma Cells is Sensitive to Inhibition by the Src Tyrosine Kinase Inhibitor AZM475271. AB - BACKGROUND: Earlier results from our group have shown that in pancreatic ductal adenocarcinoma (PDAC)-derived cells transforming growth factor (TGF)-beta1 dependent epithelial-mesenchymal transition (EMT) and cell motility was inhibited by the Src inhibitors PP2 and PP1 both of which targeted the TGF-beta receptors for inhibition. OBJECTIVE: In this study we evaluated the impact of another Src inhibitor, AZM475271, on various TGF-beta responses in PDAC cells. METHOD: The effect of AZM475271 on TGF-beta1-induced random cell migration (chemokinesis), the expression of EMT and migration/invasion-associated genes, TGF-beta-induced luciferase activity, and C-terminal phosphorylation of Smad2 and Smad3 was measured in the PDAC-derived Panc-1 and Colo357 cell lines using real-time cell migration assays, quantitative real-time PCR, luciferase reporter gene assays and phosphoimmunoblotting, respectively. RESULTS: AZM475271 effectively blocked TGF beta1-induced chemokinesis of Panc-1 cells in a dose-dependent fashion and inhibited the high chemokinetic activity of Panc-1 cells with ectopic expression of a constitutively active ALK5T204D mutant. AZM475271 but not another Src inhibitor, SU6656, partially relieved the suppressive effect of TGF-beta1 on E cadherin and inhibited TGF-beta1-induced upregulation of the MMP2, MMP9, N cadherin and vimentin genes, activity of a TGF-beta1-dependent reporter gene, and activation of Smad2 and Smad3. CONCLUSION: Our data suggest that AZM475271 cross inhibits tumor-promoting TGF-beta signaling and may thus function as an inhibitor of both TGF-beta and Src in both experimental and clinical therapies against metastatic dissemination in late-stage PDAC. PMID- 27671304 TI - Dehydroleucodine Induces a TP73-dependent Transcriptional Regulation of Multiple Cell Death Target Genes in Human Glioblastoma Cells. AB - BACKGROUND: Dehydroleucodine, a natural sesquiterpene lactone from Artemisia douglassiana Besser (Argentine) and Gynoxys verrucosa (Ecuador). OBJECTIVE: To define the molecular mechanisms underlying the effect of dehydroleucodine on the human glioblastoma cells. METHOD: Various techniques (cDNA expression array, real time quantitative PCR, chromatin immunprecipitation, luciferase reporter assay, use of phosphospecific antibodies, immunoprecipitation, immunoblotting, apoptosis and autophagy assays) were employed to define and validate multiple molecular gene targets affected in human glioblastoma cells upon dehydroleucodine exposure. RESULTS: Dehydroleucodine exposure upregulated the total and phosphorylated (p Y99) levels of TP73 in U87- MG glioblastoma cells. We found that TP73 silencing led to a partial rescue of U87-MG cells from the cell death induced by dehydroleucodine. Upon the dehydroleucodine exposure numerous gene targets were upregulated and downregulated through a TP73-dependent transcriptional mechanism. Some of these gene targets are known to be involved in cell cycle arrest, apoptosis, autophagy and necroptosis. Dehydroleucodine induced the TP73 binding to the specific genes promoters (CDKN1A, BAX, TP53AIP1, CYLD, RIPK1, and APG5L). Moreover, the exposure of U87-MG cells to dehydroleucodine upregulated the protein levels of CDKN1A, BAX, TP53AIP1, CYLD, RIPK1, APG5L, and downregulated the CASP8 level. The formation of RIPK1 protein complexes and phosphorylation of MLKL were induced by dehydroleucodine supporting the notion of multiple cell death mechanisms implicated in the tumor cell response to dehydroleucodine. CONCLUSION: This multifaceted study led to a conclusion that dehydroleucodine induces the phosphorylation of tumor protein TP73 and in turn activates numerous TP73-target genes regulating apoptosis, autophagy and necroptosis in human glioblastoma cells.. PMID- 27671305 TI - Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity. AB - BACKGROUND: Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity. AIMS: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4 substituted quinazoline pharmacophore. METHOD: Novel series of 4-substituted 6,8 dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK). RESULT: Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity. Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 MUM) with potent inhibitory percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed promising cytotoxic effects with IC50 range (12-79 MUM) with good activity against EGFR-TK with the inhibitory percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from their IC50 value (124 and 144 MUM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1% respectively. PMID- 27671306 TI - Curcumin Targets Circulating Cancer Stem Cells by Inhibiting Self-Renewal Efficacy in Non-Small Cell Lung Carcinoma. AB - BACKGROUND: The ultimate goal of the study was to find a role of curcumin in targeting lung cancer stem cells by reducing their self-renewal efficiency causing DNA damage. MATERIALS AND METHODS: Circulating lung cancer stem cells were isolated by sphere formation assay and further analysed by flow-cytometry and qRT-PCR for the presence of stem cell and stem cell transcription markers. The IC50 values of gemcitabine and curcumin were analysed by MTT assay, while curcumin induced DNA damage was scrutinized by single cell gel electrophoresis assay. RESULTS AND CONCLUSION: Our results demonstrated that curcumin significantly affect the self-renewal ability of circulating lung cancer stem cells. The no. of spheres formed in the presence of curcumin was shown to be significantly decreased. Additionally, our results depicted that 4.52+/-0.72 % and 95.47+/-0.72 % (p < 0.0001) of DNA material was found to be present in head and tail, respectively, suggesting curcumin's functional potential to cause DNA damage. Thus, we can conclude that curcumin can be used to target lung cancer stem cells which is responsible for the disease progression and metastasis by causing DNA damage or inhibiting their DNA repair mechanisms. PMID- 27671307 TI - Mechanism and Anticancer Activity of the Metabolites of an Endophytic Fungi from Eucommia ulmoides Oliv. AB - : Backgroud: Pinoresinol (Pin) and pinoresinol monoglucoside (PMG) are plant derived lignan molecules with multiple functions. We showed previously that an endophytic fungus from Eucommia ulmoides Oliv., Phomopsis sp. XP-8 is able to produce Pin and PMG. OBJECTIVE: This study was carried out to test the anti-tumor capability of the culture of XP-8 and identify the major effective compounds. METHOD: The fungal culture was added in the culture of HepG2 and K562 cells, and the viabilities of these cells were detected and the possible mechanism was analyzed. RESULT: The fungal culture showed significant capaiblity in decreasing the viability of tumor cells and induce apoptosis via up-regulation of the expression of apoptosis-related genes. It also significantly inhibited the adhesion and migration of HepG2 cells by blocking MMP-9 expression. Pin and PMG were isolated from the growth culture and shown to be the major effective components for inhibition. CONCLUSION: The study indicated the potential application of XP-8 in the production of anti-tumour products by the bioconversion of glucose. PMID- 27671308 TI - 2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth. AB - BACKGROUND: Angiogenesis is a fundamental process in the progression, invasion, and metastasis of tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular endothelial growth factor (VEFG) promoted angiogenesis. While these anti-angiogenic drugs have been commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of angiogenesis exists, which is mediated by 2-(omega-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent manner that can compensate for inhibition of the VEGF-mediated pathway. AIMS: In this work, we evaluated a CEP antibody as a new tumor growth inhibitor that blocks CEP-induced angiogenesis. METHOD: We first evaluated the effectiveness of a CEP antibody as a monotherapy to impede tumor growth in two human tumor xenograft models. We then determined the synergistic effects of bevacizumab and CEP antibody in a combination therapy, which demonstrated that blocking of the CEP-mediated pathway significantly enhanced the anti-angiogenic efficacy of bevacizumab in tumor growth inhibition indicating that CEP antibody is a promising chemotherapeutic drug. To facilitate potential translational studies of CEP-antibody, we also conducted longitudinal imaging studies and identified that FMISO-PET is a non-invasive imaging tool that can be used to quantitatively monitor the anti-angiogenic effects of CEP-antibody in the clinical setting. RESULTS: That treatment with CEP antibody induces hypoxia in tumor tissue WHICH was indicated by 43% higher uptake of [18F]FMISO in CEP antibody-treated tumor xenografs than in the control PBS-treated littermates. PMID- 27671309 TI - Evaluation of Melatonin Effect on Human Breast Cancer Stem Cells Using a Threedimensional Growth Method of Mammospheres. AB - BACKGROUND: The high rates of women's death from breast cancer occur due to acquired resistance by patients to certain treatments, enabling the recurrence and/or tumor growth, invasion and metastasis. It has been demonstrated that the presence of cancer stem cells in human tumors, as responsible for recurrence and resistance to therapy. Studies have identified OCT4 as responsible for self renewal and maintenance of pluripotency of stem cells. Thus, it is interesting to study potential drugs that target this specific population in breast cancer. Melatonin, appears to have oncostatic effects on cancer cells, however, little is known about its therapeutic effect on cancer stem cells. OBJECTIVE: Evaluate the viability and the expression of OCT4 in breast cancer stem cells, MCF-7 and MDA MB- 231, after melatonin treatment. METHOD: The cells were grown in a 3 dimensional model of mammospheres, representing the breast cancer stem cell population and treated or not with melatonin. The cell viability of mammospheres were evaluated by MTT assay and the OCT4 expression, a cancer stem cells marker, was verified by immunocitochemistry. RESULTS: Our results demonstrated that the melatonin treatment decreased the cell viability of MCF-7 and MDAMB- 231 mammospheres. Furthermore, it was observed that in both cell lines, the expression of OCT4 was decreased in melatonin-treated cells compared to the control group. CONCLUSIONS: This fact suggests that melatonin is effective against breast cancer stem cells inhibiting the cell viability via OCT 4. Based on that, we believe that melatonin has a high potential to be used as an alternative treatment for breast cancer. PMID- 27671310 TI - In Vivo Performance of a Ruthenium-cyclopentadienyl Compound in an Orthotopic Triple Negative Breast Cancer Model. AB - BACKGROUND: Ruthenium-based anti-cancer compounds are proposed as viable alternatives that might circumvent the disadvantages of platinum-based drugs, the only metallodrugs in clinical use for chemotherapy. Organometallic complexes in particular hold great potential as alternative therapeutic agents since their cytotoxicity involves different modes of action and present reduced toxicity profiles. OBJECTIVE: During the last few years our research group has been reporting on a series of organometallic ruthenium(II)- cyclopentadienyl complexes with important cytotoxicity against several cancer cell lines, surpassing cisplatin in activity. We report herein preliminary in vivo studies with one representative compound of this family, with exceptional activity against several human cancer cell lines, including the glycolytic and highly metastatic MDAMB231 cell line used in this study. METHOD: The anti-tumor activity of our compound was studied in vivo on N:NIH(S)II-nu/nu nude female mice bearing triple negative breast cancer (TNBC) orthotopic tumors. Administration of 2.5 mg/kg/day during ten days caused cell death mostly by necrosis (in vitro and in vivo), inducing tumor growth suppression of about 50% in treated animals when compared to controls. RESULTS: The most remarkable result supporting the effectiveness and potential of this drug was the absence of metastases in the main organs of treated animals, while metastases were present in the lungs of all control mice, as revealed by histopathological and immunohistochemical analysis. CONCLUSION: These in vivo studies suggest a dual effect for our drug not only by suppressing growth at the primary tumor tissue but also by inhibiting its metastatic behavior. Altogether, these results represent a benchmark and a solid starting point for future studies. PMID- 27671311 TI - Synthesis and Anti-cancer Activity of 3-substituted Benzoyl-4-substituted Phenyl 1H-pyrrole Derivatives. AB - BACKGROUND: Cancer is considered a major public health problem worldwide. OBJECTIVE: The aim of this paper is to design and synthesis of novel anticancer agents with potent anticancer activity and minimum side effects. METHOD: A series of pyrrole derivatives were synthesized, their anti-cancer activity against nine cancer cell lines and two non-cancer cell lines were evaluated by MTT assay, and their cell cycle progression were determined by flow cytometry analysis. RESULTS: The study of the structure-activity relationships revealed that the introduction of the electron-donation groups at the 4th position of the pyrrole ring increased the anti-cancer activity. Among the synthesized compounds, specially the compounds bearing 3,4-dimethoxy phenyl at the 4th position of the pyrrole ring showed potent anti-cancer activity, cpd 19 was the most potent against MGC 80-3, HCT-116 and CHO cell lines (IC50s = 1.0-1.7 MUM), cpd 21 was the most potent against HepG2, DU145 and CT-26 cell lines (IC50s = 0.5-0.9 MUM), and cpd 15 was the most potent against A549 (IC50 = 3.6 MUM). Moreover, these potent compounds showed weak cytotoxicity against HUVEC and NIH/3T3. Thus, the cpds 15, 19 and 21 show potential anti-cancer for further investigation. Furthermore, the flow cytometry analysis revealed that cpd 21 arrested the CT-26 cells at S phase, and induced the cell apoptosis. CONCLUSION: Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents. PMID- 27671312 TI - Honoring Jean-David Rochaix. AB - We honor Jean-David Rochaix, an outstanding scholar of chloroplast biogenesis and photosynthesis, who received the prestigious Lifetime Achievement Award of the International Society of Photosynthesis Research at its 17th International Photosynthesis Congress held in Maastricht, The Netherlands (August 5-12, 2016). With this award he joins other major discoverers in the field of photosynthesis: Pierre Joliot (of France, 2013); Ulrich W. Heber* (of Germany, 2010) and Kenneth Sauer (of USA, 2010); Jan M. Anderson* (of Australia, 2007); and Horst T. Witt* (of Germany, 2004). See "Appendix 1" for the list of those who have received the ISPR Communication, Innovation, Calvin-Benson, and Hill awards. PMID- 27671313 TI - Long-Term Survival of Individuals Born With Congenital Heart Disease: A Systematic Review and Meta-Analysis. PMID- 27671314 TI - Distinguishing Tachycardia Mediated From Structural Cardiomyopathy: Association of Late Gadolinium Enhancement With Recovery of Ventricular Systolic Function Following Atrial Fibrillation Ablation. PMID- 27671315 TI - Role of Early Repolarization Pattern in Increasing Risk of Death. AB - BACKGROUND: An early repolarization pattern (ERP) has been hypothesized to be arrhythmogenic in experimental studies, but the prognostic significance of the ERP in the general population is controversial. We performed a meta-analysis to examine the link between ERP and the risk of sudden cardiac arrest (SCA), cardiac death, and death from any cause. METHODS AND RESULTS: We performed a literature search using MEDLINE (January 1, 1966 to July 31, 2015) and EMBASE (January 1, 1980 to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Sixteen studies involving 334 524 subjects were identified. Compared with those without ERP, subjects with ERP experienced significantly increased risk for developing SCA (RR 2.18; 95% CI 1.29-3.68), cardiac death (RR 1.48; 95% CI 1.06-2.07), and death from any cause (RR 1.21; 95% CI 1.02-1.42), respectively. The increased risk was present predominantly in Asians and whites but not in African Americans. ERP with J-point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. ERP was associated with an absolute risk increase of 139.6 (95% CI 130.3-149.3) additional SCAs per 100 000 person-years and responsible for 7.3% (95% CI 1.9-15.2) of SCA in the general population. CONCLUSIONS: ERP is associated with significant increased risk for SCA, cardiac death, and death from any cause. Future studies should focus on understanding the exact mechanisms for the arrhythmia risk and developing reliable tools for risk stratification. PMID- 27671317 TI - Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. AB - BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV1 and whether we could mitigate reperfusion injury by limiting the calcineurin interaction with TRPV1. METHODS AND RESULTS: In primary cardiomyocytes, confocal and electron microscopy demonstrates that TRPV1 is localized to the mitochondria. Capsaicin, the specific TRPV1 agonist, dose-dependently reduced mitochondrial membrane potential and was blocked by the TRPV1 antagonist capsazepine or the calcineurin inhibitor cyclosporine. Using in silico analysis, we discovered an interaction site for TRPV1 with calcineurin. We synthesized a peptide, V1-cal, to inhibit the interaction between TRPV1 and calcineurin. In an in vivo rat myocardial infarction model, V1-cal given just prior to reperfusion substantially mitigated myocardial infarct size compared with vehicle, capsaicin, or cyclosporine (24+/ 3% versus 61+/-2%, 45+/-1%, and 49+/-2%, respectively; n=6 per group; P<0.01 versus all groups). Infarct size reduction by V1-cal was also not seen in TRPV1 knockout rats. CONCLUSIONS: TRPV1 is localized at the mitochondria in cardiomyocytes and regulates mitochondrial membrane potential through an interaction with calcineurin. We developed a novel therapeutic, V1-cal, that substantially reduces reperfusion injury by inhibiting the interaction of calcineurin with TRPV1. These data suggest that TRPV1 is an end-effector of cardioprotection and that modulating the TRPV1 protein interaction with calcineurin limits reperfusion injury. PMID- 27671316 TI - Effect of Late Gadolinium Enhancement on the Recovery of Left Ventricular Systolic Function After Pulmonary Vein Isolation. AB - BACKGROUND: The factors that predict recovery of left ventricular (LV) systolic dysfunction among patients with atrial fibrillation (AF) are not completely understood. Late gadolinium enhancement (LGE) of the LV has been reported among patients with AF, and we aimed to test whether the presence LGE was associated with subsequent recovery of LV systolic function among patients with AF and LV dysfunction. METHODS AND RESULTS: From a registry of 720 consecutive patients undergoing a cardiac magnetic resonance study prior to pulmonary vein isolation (PVI), patients with LV systolic dysfunction (ejection fraction [EF] <50%) were identified. The primary outcome was recovery of LVEF defined as an EF >50%; a secondary outcome was a combined outcome of subsequent heart failure (HF), admission, and death. Of 720 patients, 172 (24%) had an LVEF of <50% prior to PVI. The mean LVEF pre-PVI was 41+/-6% (median 43%, range 20% to 49%). Forty three patients (25%) had LGE (25 [58%] ischemic), and the extent of LGE was 7.5+/ 4% (2% to 19%). During follow-up (mean 42 months), 91 patients (53%) had recovery of LVEF, 68 (40%) had early recurrence of AF, 65 (38%) had late AF, 18 (5%) were admitted for HF, and 23 died (13%). Factors associated with nonrecovery of LVEF were older age, history of myocardial infarction, early AF recurrence, late AF recurrence, and LGE. In a multivariable model, the presence of LGE and any recurrence of AF had the strongest association with persistence of LV dysfunction. Additionally, all patients without recurrence of AF and LGE had normalization of LVEF, and recovery of LVEF was associated with reduced HF admissions and death. CONCLUSIONS: In patients with AF and LV dysfunction undergoing PVI, the absence of LGE and AF recurrence are predictors of LVEF recovery and LVEF recovery in AF with associated reduction in subsequent death and heart failure. PMID- 27671319 TI - Detection of Atrial Fibrillation Among Patients With Stroke Due to Large or Small Vessel Disease: A Meta-Analysis. AB - BACKGROUND: Recent trials have demonstrated that extended cardiac monitoring increases the yield of paroxysmal atrial fibrillation (AF) detection in patients with cryptogenic stroke. The utility of extended cardiac monitoring is uncertain among patients with stroke caused by small and large vessel disease. We conducted a meta-analysis to estimate the yield of AF detection in this population. METHODS AND RESULTS: We searched PubMed, Cochrane, and SCOPUS databases for studies on AF detection in stroke patients and excluded studies restricted to patients with cryptogenic stroke or transient ischemic attack. We abstracted AF detection rates for 3 populations grouped by stroke etiology: large vessel stroke, small vessel stroke, and stroke of undefined etiology (a mixture of cryptogenic, small vessel, large vessel, and other stroke etiologies). Our search yielded 30 studies (n=5687). AF detection rates were similar in patients with large vessel (2.2%, 95% CI 0.3-5.5; n=830) and small vessel stroke (2.4%, 95% CI 0.4-6.1; n=520). No studies had a monitoring duration longer than 7 days. The yield of AF detection in the undefined stroke population was higher (9.2%; 95% CI 7.1-11.5) compared to small vessel stroke (P=0.02) and large vessel stroke (P=0.02) populations. CONCLUSIONS: AF detection rate is similar in patients with small and large vessel strokes (2.2-2.4%). Because no studies reported on extended monitoring (>7 days) in these stroke populations, we could not estimate the yield of AF detection with long-term cardiac monitoring. Randomized controlled trials are needed to examine the utility of AF detection with long-term cardiac monitoring (>7 days) in this patient population. PMID- 27671318 TI - Irisin Inhibits Atherosclerosis by Promoting Endothelial Proliferation Through microRNA126-5p. AB - BACKGROUND: Irisin is a newly discovered myokine that has been considered a promising candidate for the treatment of cardiovascular disease through improving endothelial function. However, little is known about the role of irisin in the progression of atherosclerosis. METHODS AND RESULTS: We used a carotid partial ligation model of apolipoprotein E-deficient mice fed on a high-cholesterol diet to test the anti-atherosclerosis effect of irisin. Irisin treatment significantly suppressed carotid neointima formation. It was associated with increased endothelial cell proliferation. In addition, irisin promoted human umbilical vein endothelial cell survival via upregulating microRNA126-5p expression through the ERK signaling pathway. Inhibition of microRNA126-5p using the microRNA126-5p inhibitor abolished the prosurvival effect. The same results were demonstrated in vivo as the expression of microRNA126-5p noticeably increased in ligated carotid artery after irisin treatment. Furthermore, in vivo blockade of microRNA126-5p expression using the antagomir abolished the inhibitory effects of irisin on neointima formation, lesional lipid deposition, macrophage area, and the pro proliferation effects on endothelial cells. CONCLUSIONS: Taken together, our study demonstrates that irisin significantly reduces atherosclerosis in apolipoprotein E-deficient mice via promoting endothelial cell proliferation through microRNA126-5p, which may have a direct therapeutic effect on atherosclerotic diseases. PMID- 27671320 TI - Self-Care Disparities Among Adults with Type 2 Diabetes in the USA. AB - Suboptimal glycemic control is more common among non-Hispanic Blacks (NHBs) and Hispanics than non-Hispanic Whites (NHWs). Disparities in the performance of self care behaviors may contribute to this. To synthesize knowledge on current self care disparities, we reviewed studies from January 2011-March 2016 that included NHWs, NHBs, and Hispanics with type 2 diabetes in the USA. Self-care behaviors included diet, exercise, medications, self-monitoring of blood glucose (SMBG), self-foot exams, and not smoking. Of 1241 articles identified in PubMed, 25 met our inclusion criteria. These studies report consistent disparities in medication adherence. Surprisingly, we found consistent evidence of no disparities in exercise and some evidence of reverse disparities: compared to NHWs, Hispanics had healthier diets and NHBs had more regular SMBG. Consistent use of validated measures could further inform disparities in diet and exercise. Additional research is needed to test for disparities in self-foot exams, not smoking, and diabetes-specific problem solving and coping. PMID- 27671322 TI - Endoscopic transnasal surgery for planum and tuberculum sella meningiomas: decision-making, technique and outcomes. AB - Tuberculum sella and planum sphenoidale meningiomas pose a management challenge given their intimate relationship to surrounding critical neurovascular structures. The development and advancement of expanded endoscopic transnasal surgery has provided a good surgical option that in well-selected cases, may provide several advantages over a transcranial route. These include early devascularization, complete dura and bone removal, elimination of brain retraction and enhanced visualization of the optic apparatus perforating vessels. The authors review the endoscopic transnasal approach to these tumors and discuss surgical decision-making and case selection, surgical technique and outcomes. We also discuss the expanding role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for these challenging lesions. PMID- 27671324 TI - Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex. AB - Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT3-R, 5-HT7-R and 5-HT1D-R antagonist, 5-HT1B-R partial agonist, 5-HT1A-R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p-chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of VOR-containing food. Four groups were implanted with minipumps delivering vehicle or ESC 10 mg/kg.day s.c. The two VOR doses enable occupation by VOR of SERT+5-HT3-R and all targets, respectively, and correspond to SERT occupancies in patients treated with 5 and 20 VOR mg/day, respectively. Putative pyramidal neurons (n = 985) were recorded extracellularly in the mPFC of anesthetized rats. Sub-chronic VOR administration (but not ESC) significantly increased neuronal discharge in standard and 5-HT depleted conditions, with a greater effect of the low VOR dose in standard rats. VOR increased neuronal discharge in infralimbic (IL) and prelimbic (PrL) cortices. Hence, oral VOR doses evoking SERT occupancies similar to those in treated patients increase mPFC neuronal discharge. The effect in 5-HT-depleted rats cannot be explained by an antagonist action of VOR at 5-HT3-R and suggests a non-canonical interaction of VOR with 5-HT3-R. These effects may underlie the superior pro-cognitive efficacy of VOR compared with SSRIs in animal models. PMID- 27671323 TI - The antidepressant bupropion is a negative allosteric modulator of serotonin type 3A receptors. AB - The FDA-approved antidepressant and smoking cessation drug bupropion is known to inhibit dopamine and norepinephrine reuptake transporters, as well as nicotinic acetylcholine receptors (nAChRs) which are cation-conducting members of the Cys loop superfamily of ion channels, and more broadly pentameric ligand-gated ion channels (pLGICs). In the present study, we examined the ability of bupropion and its primary metabolite hydroxybupropion to block the function of cation-selective serotonin type 3A receptors (5-HT3ARs), and further characterized bupropion's pharmacological effects at these receptors. Mouse 5-HT3ARs were heterologously expressed in HEK-293 cells or Xenopus laevis oocytes for equilibrium binding studies. In addition, the latter expression system was utilized for functional studies by employing two-electrode voltage-clamp recordings. Both bupropion and hydroxybupropion inhibited serotonin-gated currents from 5-HT3ARs reversibly and dose-dependently with inhibitory potencies of 87 MUM and 112 MUM, respectively. Notably, the measured IC50 value for hydroxybupropion is within its therapeutically-relevant concentrations. The blockade by bupropion was largely non-competitive and non-use-dependent. Unlike its modulation at cation-selective pLGICs, bupropion displayed no significant inhibition of the function of anion selective pLGICs. In summary, our results demonstrate allosteric blockade by bupropion of the 5-HT3AR. Importantly, given the possibility that bupropion's major active metabolite may achieve clinically relevant concentrations in the brain, our novel findings delineate a not yet identified pharmacological principle underlying its antidepressant effect. PMID- 27671325 TI - Early life disruption to the ghrelin system with over-eating is resolved in adulthood in male rats. AB - Early life overweight is a significant risk factor for developmental programming of adult obesity due to changes in the availability of metabolic factors crucial for the maturation of brain appetite-regulatory circuitry. The appetite stimulating hormone, ghrelin, has been recently identified as a major regulator of the establishment of hypothalamic feeding pathways. Ghrelin exists in circulation in two major forms, as acylated and des-acylated ghrelin. While most research has focused on acyl ghrelin, the role of neonatal des-acyl ghrelin in metabolic programming is currently unknown. Here we assessed the influences of early life overfeeding on the ghrelin system, including acyl and des-acyl ghrelin's ability to access the hypothalamus in male rats. Our data show that early life overfeeding influences the ghrelin system short-term, leading to an acute reduction in circulating des-acyl ghrelin and increased expression of the growth hormone secretagogue receptor (GHSR) in the arcuate nucleus of the hypothalamus (ARC). These changes are associated with increased neuronal activation in response to exogenous acyl, but not des-acyl, ghrelin in the ARC and the paraventricular nucleus of the hypothalamus (PVN). Interestingly, while we observed no differences in the accessibility of the ARC to acyl or des-acyl ghrelin, less exogenous acyl ghrelin reaches the PVN in the neonatally overfed. Importantly, the influences of neonatal overfeeding on the ghrelin system were not maintained into adulthood. Therefore, while early life overfeeding results in excess body weight and stimulates acute changes in the brain's sensitivity to metabolic signals, this developmental mal-programming is at least partially alleviated in adulthood. PMID- 27671327 TI - Letter to the Editor Regarding: Diabetic Peripheral Neuropathy as a Predictor of Asymptomatic Myocardial Ischemia in Type 2 Diabetes Mellitus: A Cross-Sectional Study. PMID- 27671328 TI - Clinical Implications of Switching Lipid Lowering Treatment from Rosuvastatin to Other Agents in Primary Care. AB - INTRODUCTION: Switching from any statin to another non-equipotent lipid lowering treatment (LLT) may cause a low-density lipoprotein cholesterol increase and has been associated with a higher probability of negative cardiovascular outcomes. The aim of the study was to assess the impact of switching from rosuvastatin to any other LLT on clinical outcomes in primary care. METHODS: This was a retrospective analysis based on data from IMS Health Longitudinal Patient Database, which is a general practice database including information of more than 1.0 million patients representative of the Italian population by age, and medical conditions. Patients that started on rosuvastatin (10-40 mg/day) between January 2011 and December 2013 were considered. The date of the first prescription was defined as the index date (ID). The observation period lasted from the ID to September 2015 or until LLT discontinuation, or the occurrence of an acute myocardial infarction (AMI), or death. RESULTS: The primary end point of the study was the occurrence of an AMI during the observation period. The final study population included 10,368 patients. During the observation period, 2452 (23.6%) patients were switched from rosuvastatin to another LLT. The majority of patients (55.6%) were switched to atorvastatin, followed by simvastatin (24.9%), simvastatin/ezetimibe combination (10.0%) and other statins (9.5%). Female gender (HR, hazard ratio, 1.10, 95% CI, confidence interval, 1.02-1.19, p = 0.04) and the presence of chronic kidney disease (HR 1.47, 95% CI 1.16-1.86, p = 0.05) were associated with a higher probability of switch. During the observation period, 113 patients experienced an AMI (incidence of 6.7 AMI/1000 patient-years). Multivariate analysis with Cox proportional hazards method, including switching as a time-dependent covariate, demonstrated that changing from rosuvastatin to another LLT was an independent predictor of AMI (HR 2.2, 95% CI 1.4-3.5, p = 0.001). CONCLUSION: We conclude that switching from rosuvastatin to another non equipotent LLT may impart an increased risk of AMI and should be avoided. FUNDING: AstraZeneca SpA. PMID- 27671326 TI - Hip Osteoarthritis: Etiopathogenesis and Implications for Management. AB - Highly prevalent among the elderly, hip osteoarthritis (OA) carries a heavy burden of disease. Guidelines for the management of hip OA are often extrapolated from knee OA research, despite clear differences in the etiopathogenesis and response to treatments of OA at these sites. We propose that hip OA requires specific attention separate from other OA phenotypes. Our understanding of the etiopathogenesis of hip OA has seen significant advance over the last 15 years, since Ganz and colleagues proposed femoroacetabular impingement (FAI) as an important etiological factor. This narrative review summarizes the current understanding of the etiopathogenesis of hip OA and identifies areas requiring further research. Therapeutic approaches for hip OA are considered in light of the condition's etiopathogenesis. The evidence for currently adopted management strategies is considered, especially those approaches that may have disease modifying potential. We propose that shifting the focus of hip OA research and public health intervention to primary prevention and early detection may greatly improve the current management paradigm. PMID- 27671329 TI - alpha-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats. AB - This study was undertaken to investigate the effect of alpha-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (alpha-chymotrypsin, 5 mg/kg, p.o.); Group IV (alpha-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by alpha-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-kappaB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. alpha-chymotrypsin afforded significant protection against the deleterious effects of MNU. PMID- 27671330 TI - Pharmacological and toxicological evaluations of the new pyrazole compound (LQFM 021) as potential analgesic and anti-inflammatory agents. AB - Chronic inflammation is a world health problem. There is a need to develop new anti-inflammatory and analgesic drugs with improved activity and reduced side effects. In this context, the aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the pyrazole compound LQFM-021 after acute and sub-chronic administration in rats submitted to a CFA-induced chronic arthritis model, as well as compare the toxicity of this compound to that of dipyrone, given throughout 7 days. Firstly, we observed that acute oral administration of the higher dose (130 umol/kg) of LQFM-021 reduced paw lifting time (PET) and edema formation. These effects disappeared on the following day, requiring another dose to maintain the effects. This dose also promoted reduction of the polymorphonuclear recruitment in the synovial fluid. In another experiment, both treatments with LQFM-021, 65 umol/kg twice a day and 130 umol/kg once a day, produced a progressive and permanent reduction of the PET and edema, also reducing polymorphonuclear recruitment. However, the single treatment with 130 umol/kg was more effective than the double treatment with 65 umol/kg. LQFM 021 did not produce toxicity signs. However, dipyrone (130 umol/kg once a day) promoted erosion of the epithelial cells and decreased mucus in the gastric mucosa. These data indicate that LQFM-021 produced antinociceptive and anti inflammatory effects in CFA-induced arthritis in rats. These effects occurred in the absence of apparent toxic effects, indicating that the pyrazole compound LQFM 021 may be considered a good prototype for development of new analgesic/anti inflammatory drug. PMID- 27671331 TI - Pharmacological studies on the anti-inflammatory and immunomodulatory role of pentoxifylline and its interaction with nitric oxide (NO) in experimental arthritis in rats. AB - AIM: Present study was designed to evaluate protective effects of pentoxifylline and its potentiation with low dose of nitric oxide (NO) modulators in adjuvant induced experimental arthritis in rats. METHOD: Wistar rats (200-300 g, n = 8 per group) of both sexes were used in the study. On day "0" experimental arthritis was induced by injecting 0.2 ml of Complete Freund's adjuvant (CFA) in sub planter region of right hind paw of animals. Pentoxifylline treatment alone and in combination with NO modulators was given (i.p.) from day 14 to 28. Various arthritic parameters were recorded and blood and joint synovial fluid was collected for biochemical analysis. RESULTS: CFA inoculation significantly increases (1) arthritic index (2) ankle diameter (3) paw volume (4) histopathology score (5) serum TNF-alpha, IL-6, IL-1beta and synovial TNF-alpha levels (p < 0.001) (6) serum Th1 and Th2 cytokine levels g) MDA levels in rat paw tissue homogenates (7) serum NF-kappaB levels. Significant decrease in serum IL 10 levels and SOD activity was observed in rats after CFA inoculation. Decrease in body weight and suppressed general quality of life of CFA inoculated rats was also observed. These CFA-induced arthritic changes were significantly reversed by pentoxifylline alone and in combination with low dose of NO modulators (p < 0.05). CONCLUSION: These results are suggestive of protective effects of pentoxifylline and its potentiation in combination with low dose of NO modulators. These results may provide new pharmacological therapy for management of rheumatoid arthritis (RA). PMID- 27671332 TI - Study on Synergistic Mechanism of Inhibitor Mixture Based on Electron Transfer Behavior. AB - Mixing is an important method to improve the performance of surfactants due to their synergistic effect. The changes in bonding interaction and adsorption structure of IM and OP molecules before and after co-adsorbed on Fe(001) surface is calculated by DFTB+ method. It is found that mixture enable the inhibitor molecules with higher EHOMO donate more electrons while the inhibitor molecules with lower ELUMO accept more electrons, which strengthens the bonding interaction of both inhibitor agent and inhibitor additive with metal surface. Meanwhile, water molecules in the compact layer of double electric layer are repulsed and the charge transfer resistance during the corrosion process increases. Accordingly, the correlation between the frontier orbital (EHOMO and ELUMO of inhibitor molecules and the Fermi level of metal) and inhibition efficiency is determined. Finally, we propose a frontier orbital matching principle for the synergistic effect of inhibitors, which is verified by electrochemical experiments. This frontier orbital matching principle provides an effective quantum chemistry calculation method for the optimal selection of inhibitor mixture. PMID- 27671333 TI - UTX-1 regulates Tat-induced HIV-1 transactivation via changing the methylated status of histone H3. AB - Epigenetic modifications are thought to be important for gene expression changes during HIV-1 transcription and replication. The removal of histone H3 lysine27 (H3K27) trimethylation mark by UTX-1 is important for the robust induction of many specific genes during Tat-mediated HIV-1 transactvation. We found that UTX-1 enzymatic activity is needed for Tat to remove a repressive mark H3K27me3 in the HIV-1 long terminal repeat (LTR). UTX-1 converted the chromatin structure to a more transcriptionally active state by up-regulation of H3K4 methylation and down regulation of H3K27 methylation on the specific regions of HIV-1 LTR. The increase in H3K27me3 and the decrease in H3K4me3 induced by UTX-1 knockdown was detected on the HIV-1 LTR, but not by control siRNA. Additionally, UTX-1 promotes HIV-1 gene expression by enhancing both the NF-kappaB p65's nuclear translocation and its p65 binding to HIV-1 LTR. And we further demonstrated that H3K27 demethylase activity was required for increased HIV-1 transactivation induced by UTX-1. Together, our data reveal key roles for UTX-1 in a timely transition from poised to active chromatin in HIV-1 LTR during HIV-1 transcription and a fundamental mechanism by which a H3K27 demethylase triggers tissue-specific chromatin changes. Our findings provide a mechanistic link between UTX-1 and enhanced HIV-1 replication, and suggest that targeting at epigenetic mechanism may have a therapeutic benefit for HIV-1 patients. PMID- 27671334 TI - AXL Inhibition Suppresses the DNA Damage Response and Sensitizes Cells to PARP Inhibition in Multiple Cancers. AB - : Epithelial to mesenchymal transition (EMT) is associated with a wide range of changes in cancer cells, including stemness, chemo- and radio-resistance, and metastasis. The mechanistic role of upstream mediators of EMT has not yet been well characterized. Recently, we showed that non-small cell lung cancers (NSCLC) that have undergone EMT overexpress AXL, a receptor tyrosine kinase. AXL is also overexpressed in a subset of triple-negative breast cancers (TNBC) and head and neck squamous cell carcinomas (HNSCC), and its overexpression has been associated with more aggressive tumor behavior and linked to resistance to chemotherapy, radiotherapy, and targeted therapy. Because the DNA repair pathway is also altered in patient tumor specimens overexpressing AXL, it is hypothesized that modulation of AXL in cells that have undergone EMT will sensitize them to agents targeting the DNA repair pathway. Downregulation or inhibition of AXL directly reversed the EMT phenotype, led to decreased expression of DNA repair genes, and diminished efficiency of homologous recombination (HR) and RAD51 foci formation. As a result, AXL inhibition caused a state of HR deficiency in the cells, making them sensitive to inhibition of the DNA repair protein, PARP1. AXL inhibition synergized with PARP inhibition, leading to apoptotic cell death. AXL expression also associated positively with markers of DNA repair across TNBC, HNSCC, and NSCLC patient cohorts. IMPLICATIONS: The novel role for AXL in DNA repair, linking it to EMT, suggests that AXL can be an effective therapeutic target in combination with targeted therapy such as PARP inhibitors in several different malignancies. Mol Cancer Res; 15(1); 45-58. (c)2016 AACR. PMID- 27671335 TI - ECM Composition and Rheology Regulate Growth, Motility, and Response to Photodynamic Therapy in 3D Models of Pancreatic Ductal Adenocarcinoma. AB - : Pancreatic ductal adenocarcinoma is characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma associated with this disease has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how interactions with ECM, acting as a biophysical regulator of phenotype, not only a barrier to drug perfusion, regulate susceptibilities and resistance to specific therapies. In this context, an integrative approach is used to evaluate invasive behavior and motility in rheologically characterized ECM as determinants of chemotherapy and photodynamic therapy (PDT) responses. We show that in 3D cultures with ECM conditions that promote invasive progression, response to PDT is markedly enhanced in the most motile ECM-infiltrating populations, whereas the same cells exhibit chemoresistance. Conversely, drug-resistant sublines with enhanced invasive potential were generated to compare differential treatment response in identical ECM conditions, monitored by particle tracking microrheology measurements of matrix remodeling. In both scenarios, ECM infiltrating cell populations exhibit increased sensitivity to PDT, whether invasion is consequent to selection of chemoresistance, or whether chemoresistance is correlated with acquisition of invasive behavior. However, while ECM-invading, chemoresistant cells exhibit mesenchymal phenotype, induction of EMT in monolayers without ECM was not sufficient to enhance PDT sensitivity, yet does impart chemoresistance as expected. In addition to containing platform development with broader applicability to inform microenvironment-dependent therapeutics, these results reveal the efficacy of PDT for targeting the most aggressive, chemoresistant, invasive pancreatic ductal adenocarcinoma associated with dismal outcomes for this disease. IMPLICATIONS: ECM-infiltrating and chemoresistant pancreatic tumor populations exhibit increased sensitivity to PDT. Mol Cancer Res; 15(1); 15-25. (c)2016 AACR. PMID- 27671336 TI - Integrated Genetic, Epigenetic, and Transcriptional Profiling Identifies Molecular Pathways in the Development of Laterally Spreading Tumors. AB - : Laterally spreading tumors (LST) are colorectal adenomas that develop into extremely large lesions with predominantly slow progression to cancer, depending on lesion subtype. Comparing and contrasting the molecular profiles of LSTs and colorectal cancers offers an opportunity to delineate key molecular alterations that drive malignant transformation in the colorectum. In a discovery cohort of 11 LSTs and paired normal mucosa, we performed a comprehensive and unbiased screen of the genome, epigenome, and transcriptome followed by bioinformatics integration of these data and validation in an additional 84 large, benign colorectal lesions. Mutation rates in LSTs were comparable with microsatellite stable colorectal cancers (2.4 vs. 2.6 mutations per megabase); however, copy number alterations were infrequent (averaging only 1.5 per LST). Frequent genetic, epigenetic, and transcriptional alterations were identified in genes not previously implicated in colorectal neoplasia (ANO5, MED12L, EPB41L4A, RGMB, SLITRK1, SLITRK5, NRXN1, ANK2). Alterations to pathways commonly mutated in colorectal cancers, namely, the p53, PI3K, and TGFbeta pathways, were rare. Instead, LST-altered genes converged on axonal guidance, Wnt, and actin cytoskeleton signaling. These integrated omics data identify molecular features associated with noncancerous LSTs and highlight that mutation load, which is relatively high in LSTs, is a poor predictor of invasive potential. IMPLICATIONS: The novel genetic, epigenetic, and transcriptional changes associated with LST development reveal important insights into why some adenomas do not progress to cancer. The finding that LSTs exhibit a mutational load similar to colorectal carcinomas has implications for the validity of molecular biomarkers for assessing cancer risk. Mol Cancer Res; 14(12); 1217-28. (c)2016 AACR. PMID- 27671337 TI - Interplay between Cytoplasmic and Nuclear Androgen Receptor Splice Variants Mediates Castration Resistance. AB - : Androgen receptor splice variants (AR-V) are implicated in resistance of prostate cancer to androgen-directed therapies. When expressed alone in cells, some AR-Vs (e.g., AR-V7) localize primarily to the nucleus, whereas others (e.g., AR-V1, AR-V4, and AR-V6) localize mainly to the cytoplasm. Significantly, the latter are often coexpressed with the nucleus-predominant AR-Vs and the full length AR (AR-FL). An important question to be addressed is whether the cytoplasmic-localized AR-Vs play a role in castration-resistant prostate cancer (CRPC) through interaction with the nucleus-predominant AR-Vs and AR-FL. Here, it is demonstrated that AR-V1, -V4, and -V6 can dimerize with both AR-V7 and AR-FL. Consequently, AR-V7 and androgen-bound AR-FL induced nuclear localization of AR V1, -V4, and -V6, and these variants, in turn, mitigated the ability of the antiandrogen enzalutamide to inhibit androgen-induced AR-FL nuclear localization. Interestingly, the impact of nuclear localization of AR-V4 and -V6 on AR transactivation differs from that of AR-V1. Nuclear localization leads to an increased ability of AR-V4 and -V6 to transactivate both canonical AR targets and AR-V-specific targets and to confer castration-resistant cell growth. However, although AR-V1, which lacks inherent transcriptional activity, appears to activate AR-FL in an androgen-independent manner, it significantly antagonizes AR V7 transactivation. Together, these data demonstrate that the complex interactions among different AR-Vs and AR-FL play a significant role in castration-resistant disease. IMPLICATIONS: This study suggests important consequences for clinical castration resistance due to simultaneous expression of AR-FL and AR-Vs in patient tumors and suggests that dissecting these interactions should help develop effective strategies to disrupt AR-V signaling. Mol Cancer Res; 15(1); 59-68. (c)2016 AACR. PMID- 27671339 TI - Fertility-awareness practice and education in general practice. PMID- 27671338 TI - Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes. AB - Clinically useful molecular tools to triage women for a biopsy upon referral to colposcopy are not available. We aimed to develop a molecular panel to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher lesions (CIN2+) in women with abnormal cervical cytology and high-risk HPV (HPV+). We tested a biomarker panel in cervical epithelium DNA obtained from 211 women evaluated in a cervical cancer clinic in Chile from 2006 to 2008. Results were verified in a prospective cohort of 107 women evaluated in a high-risk clinic in Puerto Rico from 2013 to 2015. Promoter methylation of ZNF516, FKBP6, and INTS1 discriminated cervical brush samples with CIN2+ lesions from samples with no intraepithelial lesions or malignancy (NILM) with 90% sensitivity, 88.9% specificity, 0.94 area under the curve (AUC), 93.1% positive predictive value (PPV), and 84.2% negative predictive value (NPV). The panel results were verified in liquid-based cervical cytology samples from an independent cohort with 90.9% sensitivity, 60.9% specificity, 0.90 AUC, 52.6% PPV, and 93.3% NPV, after adding HPV16-L1 methylation to the panel. Next-generation sequencing results in HPV+ cultured cells, and urine circulating cell-free DNA (ccfDNA) were used to design assays that show clinical feasibility in a subset (n = 40) of paired plasma (AUC = 0.81) and urine (AUC = 0.86) ccfDNA samples obtained from the prospective cohort. Viral and host DNA methylation panels can be tested in liquid cytology and urine ccfDNA from women referred to colposcopy, to triage CIN2+ lesions for biopsy and inform personalized screening algorithms. Cancer Prev Res; 9(12); 915-24. (c)2016 AACR. PMID- 27671340 TI - Effects of N-acetylcysteine (NAC) supplementation in resuscitation fluids on renal microcirculatory oxygenation, inflammation, and function in a rat model of endotoxemia. AB - BACKGROUND: Modulation of inflammation and oxidative stress appears to limit sepsis-induced damage in experimental models. The kidney is one of the most sensitive organs to injury during septic shock. In this study, we evaluated the effect of N-acetylcysteine (NAC) administration in conjunction with fluid resuscitation on renal oxygenation and function. We hypothesized that reducing inflammation would improve the microcirculatory oxygenation in the kidney and limit the onset of acute kidney injury (AKI). METHODS: Rats were randomized into five groups (n = 8 per group): (1) control group, (2) control + NAC, (3) endotoxemic shock with lipopolysaccharide (LPS) without fluids, (4) LPS + fluid resuscitation, and (5) LPS + fluid resuscitation + NAC (150 mg/kg/h). Fluid resuscitation was initiated at 120 min and maintained at fixed volume for 2 h with hydroxyethyl starch (HES 130/0.4) dissolved in acetate-balanced Ringer's solution (Volulyte) with or without supplementation with NAC (150 mg/kg/h). Oxygen tension in the renal cortex (CMUPO2), outer medulla (MMUPO2), and renal vein was measured using phosphorimetry. Biomarkers of renal injury, inflammation, and oxidative stress were assessed in kidney tissues. RESULTS: Fluid resuscitation significantly improved the systemic and renal macrohemodynamic parameters after LPS. However, the addition of NAC further improved cortical renal oxygenation, oxygen delivery, and oxygen consumption (p < 0.05). NAC supplementation dampened the accumulation of NGAL or L-FABP, hyaluronic acid, and nitric oxide in kidney tissue (p < 0.01). CONCLUSION: The addition of NAC to fluid resuscitation may improve renal oxygenation and attenuate microvascular dysfunction and AKI. Decreases in renal NO and hyaluronic acid levels may be involved in this beneficial effect. A therapeutic strategy combining initial fluid resuscitation with antioxidant therapies may prevent sepsis-induced AKI. PMID- 27671341 TI - New combination of xylanolytic bacteria isolated from the lignocellulose degradation microbial consortium XDC-2 with enhanced xylanase activity. AB - Three bacterial strains with extracellular xylanase activity were isolated from the microbial consortium XDC-2. The aerobic strain A7, belonging to Bacillus sp., was combined with the anaerobe Clostridium sp. strain AA3 and/or Bacteroides sp. strain AA4 to obtain an efficient natural xylanolytic complex enzyme. The synthetic microbial community M1 consisting of strains Bacillus and Clostridium showed enhanced extracellular xylanase activity and production, and higher lignocelluloses degradation capability than any of the pure cultures and other synthetic microbial communities. Neither corn straw degradation nor extracellular xylanase activity was enhanced in the other synthetic microbial communities, Bacillus, Bacteroides with or without Clostridium. Quantitative polymerase chain reaction showed that the aerobic strain Bacillus enabled the growth of the anaerobic strain Clostridium, but not that of the anaerobic strain Bacteroides. These findings suggest that strains Bacillus and Clostridium can coexist well and have a positive synergistic interaction for extracellular xylanase secretion and lignocellulose degradation. PMID- 27671343 TI - Recent progress on biomass co-pyrolysis conversion into high-quality bio-oil. AB - Co-pyrolysis of biomass with abundantly available materials could be an economical method for production of bio-fuels. However, elimination of oxygenated compounds poses a considerable challenge. Catalytic co-pyrolysis is another potential technique for upgrading bio-oils for application as liquid fuels in standard engines. This technique promotes the production of high-quality bio-oil through acid catalyzed reduction of oxygenated compounds and mutagenic polyaromatic hydrocarbons. This work aims to review and summarize research progress on co-pyrolysis and catalytic co-pyrolysis, as well as their benefits on enhancement of bio-oils derived from biomass. This review focuses on the potential of plastic wastes and coal materials as co-feed in co-pyrolysis to produce valuable liquid fuel. This paper also proposes future directions for using this technique to obtain high yields of bio-oils. PMID- 27671342 TI - Pyrolysis of hornbeam (Carpinus betulus L.) sawdust: Characterization of bio-oil and bio-char. AB - Slow pyrolysis of hornbeam (Carpinus betulus L.) sawdust was performed to produce bio-oil and bio-char. The operational variables were as follows: pyrolysis temperature (400-600 degrees C), heating rate (10-50 degrees Cmin-1) and nitrogen flow rate (50-150cm3min-1). Physicochemical and thermogravimetric characterizations of hornbeam sawdust were performed. The characteristics of bio oil and bio-char were analyzed on the basis of various spectroscopic and chromatographic techniques such as FTIR, GC-MS, 1H NMR, SEM, BET. Higher heating value, density and kinematic viscosity of the bio-oil with maximum yield of 35.28% were 23.22MJkg-1, 1289kgm-3 and 0.6mm2s-1, respectively. The bio-oil with relatively high fuel potential can be obtained from the pyrolysis of the hornbeam sawdust and the bio-char with a calorific value of 32.88MJkg-1 is a promising candidate for solid fuel applications that also contributes to the preservation of the environment. PMID- 27671344 TI - Characterization of the molecular mechanism of 5-lipoxygenase inhibition by 2 aminothiazoles. AB - 5-Lipoxygenase (5-LO, EC1.13.11.34) has been implicated in the pathogenesis of inflammatory and immune diseases. Recently, aminothiazole comprising inhibitors have been discovered for this valuable target. Yet, the molecular mode of action of this class of substances is only poorly understood. Here, we present the detailed molecular mechanism of action of the compound class and the in vitro pharmacological profile of two lead compounds ST-1853 and ST-1906. Mechanistic studies with recombinant proteins as well as intact cell assays enabled us to define this class as a novel type of 5-LO inhibitors with unique characteristics. The parent compounds herein presented a certain reactivity concerning oxidation and thiol binding: Unsubstituted aminophenols bound covalently to C159 and C418 of human 5-LO. Yet, dimethyl substitution of the aminophenol prevented this reactivity and slowed down phase II metabolism. Both ST-1853 and ST-1906 confirmed their lead likeness by retaining their high potency in physiologically relevant 5-LO activity assays, high metabolic stability, high specificity and non cytotoxicity. PMID- 27671345 TI - Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1beta. AB - BACKGROUND: It is widely accepted that neuroinflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD) and high levels of cytokines and chemokines are detected around Abeta plaques. METHODS: As neuroinflammation is involved in the development and progression of AD, we measured the pro-inflammatory cytokines interleukin 1beta (IL-1beta), IL-8 and tumor necrosis factor alpha (TNF-alpha) in serum and cerebrospinal fluid (CSF) samples from 45 AD patients and 53 age-matched control subjects using a highly sensitive multiplex electrochemiluminescence assay. To address the association with disease progression we correlated cognitive status with cytokine levels. RESULTS: CSF as well as serum IL-8 levels were found to be significantly lower in AD patients than in controls (p = 0.02). A statistically significant inverse correlation was observed between the CSF level of IL-1beta and the MMSE score (rs = -0.03, p = 0.02). We therefore stratified the AD patients by their MMSE scores into three equal groups and found that in the AD group with the most severe cognitive impairment CSF-IL-1beta was significantly increased compared to age matched controls (p < 0.05), whereas in the other investigated groups the increase was not statistically significant. CONCLUSION: Our results confirm data suggesting that cytokine alterations are involved in AD pathogenesis and may be helpful as a biomarker for monitoring disease progression. PMID- 27671347 TI - Cobalt phosphide nanowall array as an efficient 3D catalyst electrode for methanol electro-oxidation. AB - In this letter, we report on the use of a cobalt phosphide nanowall array on conductive carbon cloth (CoP NA/CC) as an efficient catalyst electrode for methanol electro-oxidation under alkaline conditions. This CoP NA/CC achieves a current density of 96 mA cm(-2) toward 0.5 M methanol at 0.5 V (versus a saturated calomel electrode (SCE)) in 1 M KOH. Moreover, this electrode exhibits superior stability and 93% of the initial anodic current density can be retained after 1000 cyclic voltammetry cycles when re-measured in new electrolyte. PMID- 27671346 TI - A multiplex PCR for detection of Listeria monocytogenes and its lineages. AB - A novel multiplex PCR assay was developed to identify genus Listeria, and discriminate Listeria monocytogenes and its major lineages (LI, LII, LIII). This assay is a rapid and inexpensive subtyping method for screening and characterization of L. monocytogenes. PMID- 27671348 TI - A treatment planning study comparing tomotherapy, volumetric modulated arc therapy, Sliding Window and proton therapy for low-risk prostate carcinoma. AB - BACKGROUND: Comparing radiation treatment plans to ascertain the optimal intensity-modulated radiation technique for low-risk prostate cancer. METHODS: Treatment plans for 20 randomly selected patients were generated using the same dose objectives. A dosimetric comparison was performed between various intensity modulated techniques, including protons. All treatment plans provided conventional treatment with 79.2Gy. Dosimetric indices for the target volume and organs at risk (OAR), including homogeneity index and four conformity indices were analyzed. RESULTS: No statistically significant differences between techniques were observed for homogeneity values. Dose distributions showed significant differences at low-to-medium doses. At doses above 50Gy all techniques revealed a steep dose gradient outside the planning target volume (PTV). Protons demonstrated superior rectum sparing at low-to-higher doses (V10 V70, P < .05) and bladder sparing at low-to-medium doses (V10-V30, P < .05). Helical tomotherapy (HT) provided superior rectum sparing compared to Sliding Window (SW) and Rapid Arc (RA) (V10-V70, P < .05). SW displayed superior bladder sparing compared to HT and RA (V10-V50, P < .05). Protons generated significantly higher femoral heads exposure and HT had superior sparing of those. CONCLUSION: All techniques are able to provide a homogeneous and highly conformal dose distribution. Protons demonstrated superior sparing of the rectum and bladder at a wide dose spectrum. The radiation technique itself as well as treatment planning algorithms result in different OAR sparing between HT, SW and RA, with superior rectum sparing by HT and superior bladder sparing by SW. Radiation plans can be further optimized by individual modification of dose objectives dependent on treatment plan strategy. PMID- 27671349 TI - A soft decoding algorithm and hardware implementation for the visual prosthesis based on high order soft demodulation. AB - BACKGROUND: High order modulation and demodulation technology can solve the frequency requirement between the wireless energy transmission and data communication. In order to achieve reliable wireless data communication based on high order modulation technology for visual prosthesis, this work proposed a Reed Solomon (RS) error correcting code (ECC) circuit on the basis of differential amplitude and phase shift keying (DAPSK) soft demodulation. Firstly, recognizing the weakness of the traditional DAPSK soft demodulation algorithm based on division that is complex for hardware implementation, an improved phase soft demodulation algorithm for visual prosthesis to reduce the hardware complexity is put forward. Based on this new algorithm, an improved RS soft decoding method is hence proposed. In this new decoding method, the combination of Chase algorithm and hard decoding algorithms is used to achieve soft decoding. In order to meet the requirements of implantable visual prosthesis, the method to calculate reliability of symbol-level based on multiplication of bit reliability is derived, which reduces the testing vectors number of Chase algorithm. The proposed algorithms are verified by MATLAB simulation and FPGA experimental results. During MATLAB simulation, the biological channel attenuation property model is added into the ECC circuit. RESULTS: The data rate is 8 Mbps in the MATLAB simulation and FPGA experiments. MATLAB simulation results show that the improved phase soft demodulation algorithm proposed in this paper saves hardware resources without losing bit error rate (BER) performance. Compared with the traditional demodulation circuit, the coding gain of the ECC circuit has been improved by about 3 dB under the same BER of [Formula: see text]. The FPGA experimental results show that under the condition of data demodulation error with wireless coils 3 cm away, the system can correct it. The greater the distance, the higher the BER. Then we use a bit error rate analyzer to measure BER of the demodulation circuit and the RS ECC circuit with different distance of two coils. And the experimental results show that the RS ECC circuit has about an order of magnitude lower BER than the demodulation circuit when under the same coils distance. Therefore, the RS ECC circuit has more higher reliability of the communication in the system. CONCLUSIONS: The improved phase soft demodulation algorithm and soft decoding algorithm proposed in this paper enables data communication that is more reliable than other demodulation system, which also provide a significant reference for further study to the visual prosthesis system. PMID- 27671350 TI - Apelin binding to human APJ receptor leads to biased signaling. AB - BACKGROUND: Human APJ receptor (APJR), a rhodopsin family G-Protein Coupled Receptor (GPCR), activated by isoforms of peptide ligand apelin causing potent inotropic effect, is involved in cardiac function, angiogenesis and maintenance of fluid homeostasis. APJR is expressed in various organs e.g., heart, brain, kidney, muscles, etc. Hence, problems in APJR signaling lead to severe dysregulation in the pathophysiology of an organism. METHODS: Based on multiple sequence alignment of receptors from various organisms, we observe a large number of conserved residues in the extracellular side. Mutational studies including calcium mobilization, receptor internalization and ERK1/2 phosphorylation assays were performed. RESULTS: Stimulation of APJR and its mutants with apelin-13 led to mutation-dependent variation in receptor activation, intracellular Ca2+rise, and its subsequent downstream signaling. The mutant 183MDYS186-AAAA in ECL2 showed Gi-biased signaling while 268KTL270-AAA in ECL3 showed Gq biasing. C281A mutant in ECL3 was deficient in all assays. CONCLUSION: Conserved residues in the ECL2 of APJR are key for ligand binding, activation mechanism, and selective downstream signaling. Additionally, we demonstrate that Cys281 (in ECL3) mediated disulfide linkage is important for ligand recognition and receptor activation. GENERAL SIGNIFICANCE: This work explains the importance of extracellular loop domains in ligand binding, receptor activation and downstream signaling of human APJR. PMID- 27671351 TI - Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple transgenic mouse model of Alzheimer's disease. AB - Recently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APP)SWE/presenilin-1 (PS1)M146V/TauP301L mouse (3*Tg-AD) model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms. NSTK could increase spontaneous locomotor activity in the open field and low anxiety-like behavior in the elevated plus maze, and improve the spatial memory deficits in the Morris water maze. The biochemical analysis suggested that NSTK could decrease Abeta42 deposition, abnormal tau aggregation, and the expressions of p-APP Thr668, PS1 and p-tau Ser202/Thr205 in the hippocampus of 3*Tg-AD mice. Consistently, NSTK could reduce the level of malondialdehyde, increase the activity of superoxide dismutase and catalase. Up-regulation of Bcl 2, and down-regulation of BAX, caspase-3 and inflammatory cytokines also occurred in the hippocampus of 3*Tg-AD mice after treatment with NSTK. Thus, NSTK could intervene in multiple pathological processes of AD and would be a drug candidate against AD. PMID- 27671352 TI - The impact of sequence database choice on metaproteomic results in gut microbiota studies. AB - BACKGROUND: Elucidating the role of gut microbiota in physiological and pathological processes has recently emerged as a key research aim in life sciences. In this respect, metaproteomics, the study of the whole protein complement of a microbial community, can provide a unique contribution by revealing which functions are actually being expressed by specific microbial taxa. However, its wide application to gut microbiota research has been hindered by challenges in data analysis, especially related to the choice of the proper sequence databases for protein identification. RESULTS: Here, we present a systematic investigation of variables concerning database construction and annotation and evaluate their impact on human and mouse gut metaproteomic results. We found that both publicly available and experimental metagenomic databases lead to the identification of unique peptide assortments, suggesting parallel database searches as a mean to gain more complete information. In particular, the contribution of experimental metagenomic databases was revealed to be mandatory when dealing with mouse samples. Moreover, the use of a "merged" database, containing all metagenomic sequences from the population under study, was found to be generally preferable over the use of sample-matched databases. We also observed that taxonomic and functional results are strongly database dependent, in particular when analyzing the mouse gut microbiota. As a striking example, the Firmicutes/Bacteroidetes ratio varied up to tenfold depending on the database used. Finally, assembling reads into longer contigs provided significant advantages in terms of functional annotation yields. CONCLUSIONS: This study contributes to identify host- and database-specific biases which need to be taken into account in a metaproteomic experiment, providing meaningful insights on how to design gut microbiota studies and to perform metaproteomic data analysis. In particular, the use of multiple databases and annotation tools has to be encouraged, even though this requires appropriate bioinformatic resources. PMID- 27671353 TI - Pupillary reactivity to negative stimuli prospectively predicts recurrence of major depressive disorder in women. AB - There is a large body of research supporting the association between disrupted physiological reactivity to negative stimuli and depression. The present study aimed to examine whether physiological reactivity to emotional stimuli, assessed via pupil dilation, served as a biological marker of risk for depression recurrence among individuals who are known to be at a higher risk due to having previous history of depression. Participants were 57 women with a history of major depressive disorder (MDD). Pupil dilation to angry, happy, sad, and neutral faces was recorded. Participants' diagnoses and symptoms were assessed 24 months after the initial assessment. We found that women's pupillary reactivity to negative (sad or angry faces) but not positive stimuli prospectively predicted MDD recurrence. Additionally, we found that both hyper- and hypopupillary reactivity to angry faces predicted risk for MDD recurrence. These findings suggest that disrupted physiological response to negative stimuli indexed via pupillary dilation could serve as a physiological marker of MDD risk, thus presenting clinicians with a convenient and inexpensive method to predict which of the at-risk women are more likely to experience depression recurrence. PMID- 27671354 TI - JMJD8 is a positive regulator of TNF-induced NF-kappaB signaling. AB - TNF-induced signaling mediates pleiotropic biological consequences including inflammation, immunity, cell proliferation and apoptosis. Misregulation of TNF signaling has been attributed as a major cause of chronic inflammatory diseases and cancer. Jumonji domain-containing protein 8 (JMJD8) belongs to the JmjC family. However, only part of the family members has been described as hydroxylase enzymes that function as histone demethylases. Here, we report that JMJD8 positively regulates TNF-induced NF-kappaB signaling. Silencing the expression of JMJD8 using RNA interference (RNAi) greatly suppresses TNF-induced expression of several NF-kappaB-dependent genes. Furthermore, knockdown of JMJD8 expression reduces RIP ubiquitination, IKK kinase activity, delays IkappaBalpha degradation and subsequently blocks nuclear translocation of p65. In addition, JMJD8 deficiency enhances TNF-induced apoptosis. Taken together, these findings indicate that JMJD8 functions as a positive regulator of TNF-induced NF-kappaB signaling. PMID- 27671356 TI - Making sense of genetic estimates of effective population size. AB - The last decade has seen an explosion of interest in use of genetic markers to estimate effective population size, Ne . Effective population size is important both theoretically (Ne is a key parameter in almost every aspect of evolutionary biology) and for practical application (Ne determines rates of genetic drift and loss of genetic variability and modulates the effectiveness of selection, so it is crucial to consider in conservation). As documented by Palstra & Fraser (), most of the recent growth in Ne estimation can be attributed to development or refinement of methods that can use a single sample of individuals (the older temporal method requires at least two samples separated in time). As with other population genetic methods, performance of new Ne estimators is typically evaluated with simulated data for a few scenarios selected by the author(s). Inevitably, these initial evaluations fail to fully consider the consequences of violating simplifying assumptions, such as discrete generations, closed populations of constant size and selective neutrality. Subsequently, many researchers studying natural or captive populations have reported estimates of Ne for multiple methods; often these estimates are congruent, but that is not always the case. Because true Ne is rarely known in these empirical studies, it is difficult to make sense of the results when estimates differ substantially among methods. What is needed is a rigorous, comparative analysis under realistic scenarios for which true Ne is known. Recently, Gilbert & Whitlock () did just that for both single-sample and temporal methods under a wide range of migration schemes. In the current issue of Molecular Ecology, Wang () uses simulations to evaluate performance of four single-sample Ne estimators. In addition to assessing effects of true Ne , sample size, and number of loci, Wang also evaluated performance under changing abundance, physical linkage and genotyping errors, as well as for some alternative life histories (high rates of selfing; haplodiploids). Wang showed that the sibship frequency (SF) and linkage disequilibrium (LD) methods perform dramatically better than the heterozygote excess and molecular coancestry methods under most scenarios (see Fig. 1, modified from figure 2 in Wang ), and he also concluded that SF is generally more versatile than LD. This article represents a truly Herculean effort, and results should be of considerable value to researchers interested in applying these methods to real-world situations. PMID- 27671358 TI - Monte Carlo simulation algorithm for B-DNA. AB - Understanding the structure-function relationship of biomolecules containing DNA has motivated experiments aimed at determining molecular structure using methods such as small-angle X-ray and neutron scattering (SAXS and SANS). SAXS and SANS are useful for determining macromolecular shape in solution, a process which benefits by using atomistic models that reproduce the scattering data. The variety of algorithms available for creating and modifying model DNA structures lack the ability to rapidly modify all-atom models to generate structure ensembles. This article describes a Monte Carlo algorithm for simulating DNA, not with the goal of predicting an equilibrium structure, but rather to generate an ensemble of plausible structures which can be filtered using experimental results to identify a sub-ensemble of conformations that reproduce the solution scattering of DNA macromolecules. The algorithm generates an ensemble of atomic structures through an iterative cycle in which B-DNA is represented using a wormlike bead-rod model, new configurations are generated by sampling bend and twist moves, then atomic detail is recovered by back mapping from the final coarse-grained configuration. Using this algorithm on commodity computing hardware, one can rapidly generate an ensemble of atomic level models, each model representing a physically realistic configuration that could be further studied using molecular dynamics. (c) 2016 Wiley Periodicals, Inc. PMID- 27671357 TI - Measuring Adolescent Human Papillomavirus Vaccine Coverage: A Match of Sexually Transmitted Disease Clinic and Immunization Registry Data. AB - PURPOSE: Human papillomavirus (HPV) vaccine is recommended for adolescents. By the end of 2013, 64% of female and 40% of male New York City residents aged 13-18 years had received >=1 HPV vaccine dose. Adolescents attending sexually transmitted disease (STD) clinics are at high risk for HPV exposure and could benefit from vaccination. Our objective was to estimate HPV vaccination coverage for this population. METHODS: We matched records of New York City's STD clinic patients aged 13-18 years during 2010-2013 with the Citywide Immunization Registry. We assessed HPV vaccine initiation (>=1 dose) and series completion (>=3 doses among those who initiated) as of clinic visit date and by patient demographics. We compared receipt of >=1 dose for HPV, tetanus-diphtheria acellular pertussis, and meningococcal conjugate vaccine. RESULTS: Eighty-two percent of clinic attendees (13,505/16,364) had records in the Citywide Immunization Registry. Receipt of >=1 HPV dose increased during 2010-2013 (females: 57.6%-69.7%; males: 1.5%-36.3%). Among females, >=1-dose coverage was lowest among whites (53.4%) and highest among Hispanics (73.3%); among males, >=1 dose coverage was lowest among whites (6.9%) and highest among Asians (20.9%). Series completion averaged 57.7% (females) and 28.0% (males), with little variation by race/ethnicity or poverty level. Receipt of >=1 dose was 59.7% for HPV, 82% for tetanus-diphtheria-acellular pertussis, and 76% for meningococcal conjugate vaccines. CONCLUSIONS: HPV vaccine initiation and completion were low among adolescent STD clinic patients; coverage was lower compared with other recommended vaccines. STD clinics may be good venues for delivering HPV vaccine, thereby enhancing efforts to improve HPV vaccination. PMID- 27671355 TI - Staphylococcus aureus SufT: an essential iron-sulphur cluster assembly factor in cells experiencing a high-demand for lipoic acid. AB - Staphylococcus aureus SufT is composed solely of the domain of unknown function 59 (DUF59) and has a role in the maturation of iron-sulphur (Fe-S) proteins. We report that SufT is essential for S. aureus when growth is heavily reliant upon lipoamide-utilizing enzymes, but dispensable when this reliance is decreased. LipA requires Fe-S clusters for lipoic acid (LA) synthesis and a DeltasufT strain had phenotypes suggestive of decreased LA production and decreased activities of lipoamide-requiring enzymes. Fermentative growth, a null clpC allele, or decreased flux through the TCA cycle diminished the demand for LA and rendered SufT non-essential. Abundance of the Fe-S cluster carrier Nfu was increased in a DeltaclpC strain and a null clpC allele was unable to suppress the LA requirement of a DeltasufT Deltanfu strain. Over-expression of nfu suppressed the LA requirement of the DeltasufT strain. We propose a model wherein SufT, and by extension the DUF59, is essential for the maturation of holo-LipA in S. aureus cells experiencing a high demand for lipoamide-dependent enzymes. The findings presented suggest that the demand for products of Fe-S enzymes is a factor governing the usage of one Fe-S cluster assembly factor over another in the maturation of apo-proteins. PMID- 27671359 TI - A QTAIM and stress tensor investigation of the torsion path of a light-driven fluorene molecular rotary motor. AB - The utility of the QTAIM/stress tensor analysis method for characterizing the photoisomerization of light driven molecular rotary machines is investigated on the example of the torsion path in fluorene molecular motor. The scalar and vector descriptors of QTAIM/stress tensor reveal additional information on the bonding interactions between the rotating units of the motor, which cannot be obtained from the analysis of the ground and excited state potential energy surfaces. The topological features of the fluorene motor molecular graph display that, upon the photoexcitation a certain increase in the torsional stiffness of the rotating bond can be attributed to the increasing topological stability of the rotor carbon atom attached to the rotation axle. The established variations in the torsional stiffness of the rotating bond may cause transfer of certain fraction of the torsional energy to other internal degrees of freedom, such as the pyramidalization distortion. (c) 2016 Wiley Periodicals, Inc. PMID- 27671360 TI - Sex differences in the risk factors for Staphylococcus aureus throat carriage. AB - BACKGROUND: Male gender and adiposity are considered to be risk factors for Staphylococcus aureus carriage. We tested whether colonization is related to free testosterone (fT) level and adiposity, measured with body mass index (BMI) and body fat percentage (BFP), in healthy adults. METHODS: Blood sample and throat swabs were taken twice (at 4-week intervals) from healthy men and women aged 18 36 years. fT level, height, weight, and BFP were measured. Participants were classified as persistent carriers, intermittent carriers (excluded from the analyses), and noncarriers. The final sample was 152 participants: 85 men and 67 women. RESULTS: BFP, but not BMI, correlated positively with S aureus colonization (P = .02) in men. BMI became a significant predictor of carriage only when comparing groups within and above norms (P = .04). There was no relationship for BMI nor BFP in women. Higher fT level was related to persistent carriage (P = .02) in women, there was no relationship for fT level in men. CONCLUSION: Risk factors for S aureus carriage are sex dependent. Within-sex variation in colonization is related to fT level in women, whereas in men it is related to the amount of body fat. PMID- 27671361 TI - Bacterial contamination of nurses' white coats after first and second shift. AB - Microbial load of nurses' white coats in a hospital was determined on polyester cotton blend and polyester fabric after the first and second work shift. Contamination on the blend fabric was significantly higher (P < .05) than on polyester. After the second shift, bacterial colonies on polyester and blend fabrics increased by ~98% and ~70%, respectively. Among the isolates detected on polyester after the second shift, Escherichia coli was the most abundant (47.8%), followed by staphylococci (19.1%). PMID- 27671362 TI - Call for improvement in personal protective equipment guidance and research. PMID- 27671363 TI - Handwashing, but how? Microbial effectiveness of existing handwashing practices in high-density suburbs of Harare, Zimbabwe. AB - BACKGROUND: Consistent domestic hand hygiene can reduce diarrhea-related morbidity and mortality and the spread of other communicable diseases. However, it remains uncertain which technique of handwashing is most effective and practicable during everyday life. The goal of this study is to determine how the handwashing technique, as performed in the daily life by the participants of this case study in Harare, Zimbabwe, influences microbial handwashing effectiveness. METHODS: Handwashing technique of 173 primary caregivers was observed in their homes and hand rinse samples were collected before and after handwashing. Samples were analyzed for Escherichia coli and total coliform concentrations. Generalized linear models were used to predict fecal hand contamination after washing from observed handwashing technique. RESULTS: Cleaning under fingernails, scrubbing the fingertips, using soap, and drying hands through rubbing on clothes or a clean towel statistically significantly reduced E coli contamination of hands after washing. Tap use, scrubbing fingertips, and rubbing hands on clothes to dry them statistically significantly reduced total coliform contamination. CONCLUSIONS: Recommendations for effective and practicable domestic handwashing in Harare, Zimbabwe, should include performing specific handscrubbing steps (ie, cleaning under the fingernails and rubbing the fingertips), and soap and tap use. This calls for further research to develop behavior change interventions that explicitly promote effective handwashing technique at critical times. PMID- 27671364 TI - Characterization of Pectobacterium carotovorum proteins differentially expressed during infection of Zantedeschia elliotiana in vivo and in vitro which are essential for virulence. AB - The identification of phytopathogen proteins that are differentially expressed during the course of the establishment of an infection is important to better understand the infection process. In vitro approaches, using plant extracts added to culture medium, have been used to identify such proteins, but the biological relevance of these findings for in planta infection are often uncertain until confirmed by in vivo studies. Here, we compared the proteins of Pectobacterium carotovorum ssp. carotovorum strain PccS1 differentially expressed in Luria Bertani medium supplemented with extracts of the ornamental plant Zantedeschia elliotiana cultivar 'Black Magic' (in vitro) and in plant tissues (in vivo) by two-dimensional electrophoresis coupled with mass spectrometry. A total of 53 differentially expressed proteins (>1.5-fold) were identified (up-regulated or down-regulated in vitro, in vivo or both). Proteins that exhibited increased expression in vivo but not in vitro, or in both conditions, were identified, and deletions were made in a number of genes encoding these proteins, four of which (clpP, mreB, flgK and eda) led to a loss of virulence on Z. elliotiana, although clpP and mreB were later also shown to be reduced in growth in rich and minimal media. Although clpP, flgK and mreB have previously been reported as playing a role in virulence in plants, this is the first report of such a role for eda, which encodes 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, a key enzyme in Entner-Doudoroff metabolism. The results highlight the value of undertaking in vivo as well as in vitro approaches for the identification of new bacterial virulence factors. PMID- 27671366 TI - Triggers for Preeclampsia Onset: a Case-Crossover Study. AB - BACKGROUND: Risk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset. METHODS: We used a case-crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of >=20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP >=140 mmHg and/or >=90 mmHg) and proteinuria (protein/creatinine ratio >=30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1-7 days preceding diagnosis of preeclampsia) and control windows (8-14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported. RESULTS: Among 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8-14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset. CONCLUSION: Recent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia. PMID- 27671367 TI - De-novo transcriptome assembly for gene identification, analysis, annotation, and molecular marker discovery in Onobrychis viciifolia. AB - BACKGROUND: Sainfoin (Onobrychis viciifolia) is a highly nutritious tannin containing forage legume. In the diet of ruminants sainfoin can have anti parasitic effects and reduce methane emissions under in vitro conditions. Many of these benefits have been attributed to condensed tannins or proanthocyanidins in sainfoin. A combination of increased use of industrially produced nitrogen fertilizer, issues with establishment and productivity in the first year and more reliable alternatives, such as red clover led to a decline in the use of sainfoin since the middle of the last century. In recent years there has been a resurgence of interest in sainfoin due to its potential beneficial nutraceutical and environmental attributes. However, genomic resources are scarce, thus hampering progress in genetic analysis and improvement. To address this we have used next generation RNA sequencing technology to obtain the first transcriptome of sainfoin. We used the library to identify gene-based simple sequence repeats (SSRs) and potential single nucleotide polymorphisms (SNPs). RESULTS: One genotype from each of five sainfoin accessions was sequenced. Paired-end (PE) sequences were generated from cDNA libraries of RNA extracted from 7 day old seedlings. A combined assembly of 92,772 transcripts was produced de novo using the Trinity programme. About 18,000 transcripts were annotated with at least one GO (gene ontology) term. A total of 63 transcripts were annotated as involved in the tannin biosynthesis pathway. We identified 3786 potential SSRs. SNPs were identified by mapping the reads of the individual assemblies against the combined assembly. After stringent filtering a total of 77,000 putative SNPs were identified. A phylogenetic analysis of single copy number genes showed that sainfoin was most closely related to red clover and Medicago truncatula, while Lotus japonicus, bean and soybean are more distant relatives. CONCLUSIONS: This work describes the first transcriptome assembly in sainfoin. The 92 K transcripts provide a rich source of SNP and SSR polymorphisms for future use in genetic studies of this crop. Annotation of genes involved in the condensed tannin biosynthesis pathway has provided the basis for further studies of the genetic control of this important trait in sainfoin. PMID- 27671365 TI - Predictable threats to public health through delaying universal access to innovative medicines for hepatitis C: a pharmaceutical standpoint. PMID- 27671368 TI - Potential of the Cnidium monnieri fruits as an immune enhancer in Escherichia coli infection model. AB - OBJECTIVES: The Cnidium monnieri fruits (CMF) were studied how they act on immune system as a novel immunostimulator against the infectious disease. METHODS: Macrophages were treated with CMF, and nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) were measured, and phagocytosis of macrophages was detected using FITC-labelled Escherichia coli. The protective effect of CMF against E. coli infection in mice was examined. The survival rate was monitored daily for up to 5 days. And then the viable bacteria count of serum and the immunological mediator (NO, TNF-alpha, interleukin (IL)-12 and IL-6) of serum, splenocyte and peritoneal macrophages were analysed. KEY FINDINGS: The CMF significantly enhanced the concentrations of NO and TNF-alpha and the phagocytosis activity in macrophages. The oral administration of CMF for five consecutive days before infection prolonged the survival rate. Treatment with CMF significantly stimulated the phagocytosis of peritoneal macrophages and induced the immunological mediator of serum, splenocyte and peritoneal macrophages against the E. coli infection. CONCLUSIONS: The host-protective effects of CMF might be archived by improving immune response, and CMF could act to prevent pathogenic microbial infections with immunomodulation. PMID- 27671369 TI - Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non-malignant diseases. AB - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of non-malignant conditions. However, these children face an increased risk of late death and incident cancers after HSCT, which may occur many years after their initial HSCT. PROCEDURE: We examined cancer occurrence and late mortality in a population-based cohort of 318 Australian children who underwent allogeneic HSCT for non-malignant disease. Standardized incident ratios (SIRs) and standardized mortality ratios (SMRs) were calculated and compared with population controls. RESULTS: We identified six (1.9%) cancers at a median 9.2 years post-HSCT. Cancer occurred 15 times more frequently than in the general population (SIR 15.4, 95% CI = 6.9-34.2). Of the 198 patients who survived for at least 2 years post-HSCT, 11 (5.6%) died at a median 7.5 years post-HSCT. The mortality rate was 17 times higher than in the general population (SMR 17.5, 95% CI = 9.7-31.2). DISCUSSION: Children transplanted for non-malignant conditions require evidence-based survivorship programs to reduce excess morbidity and mortality. PMID- 27671370 TI - Comparison of screening for pre-eclampsia at 31-34 weeks' gestation by sFlt 1/PlGF ratio and a method combining maternal factors with sFlt-1 and PlGF. AB - OBJECTIVE: To estimate the patient-specific risk of pre-eclampsia (PE) at 31-34 weeks' gestation by a combination of maternal characteristics and medical history with multiples of the median (MoM) values of serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) and to compare the performance of screening to that achieved by the sFlt-1/PlGF ratio. METHODS: This was a prospective observational study in women attending a third-trimester ultrasound scan at 31-34 weeks as part of routine pregnancy care. We estimated the performance of screening for PE with delivery within 4 weeks of assessment and PE with delivery from 4 weeks after assessment up to 40 weeks' gestation by the sFlt-1/PlGF ratio and by a method utilizing Bayes' theorem that combines maternal factors and MoM values of sFlt-1 and PlGF. The significance of the difference in screening performance between the two methods was assessed by comparison of the areas under the receiver-operating characteristics curves (AUC). RESULTS: The study population of 8063 singleton pregnancies included 231 (2.9%) that subsequently developed PE. In the prediction of delivery with PE at < 4 weeks from assessment, the performance of the method utilizing Bayes' theorem was similar to that using the sFlt-1/PlGF ratio (AUC, 0.987 (95% CI, 0.979-0.995) vs 0.988 (95% CI, 0.981-0.994); P = 0.961). In contrast, the performance of screening for delivery with PE at >= 4 weeks after assessment up to 40 weeks' gestation was better with the method utilizing Bayes' theorem than that with the sFlt-1/PlGF ratio (AUC, 0.884 (95% CI, 0.854-0.914) vs 0.818 (95% CI, 0.775 0.860); P < 0.0001). CONCLUSION: At 31-34 weeks' gestation the performance of screening for PE delivering at < 4 weeks from assessment by the method utilizing Bayes' theorem is similar to that using the sFlt-1/PlGF ratio, but the former is superior to the latter in prediction of PE delivering >= 4 weeks from assessment. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27671371 TI - Changes in disc status in the reducing and nonreducing anterior disc displacement of temporomandibular joint: a longitudinal retrospective study. AB - Treatment procedures for anterior disc displacement (ADD) of temporomandibular joint (TMJ) are far from reaching a consensus. The aim of the study was to evaluate disc status changes of anterior disc displacement with reduction (ADDWR) and without reduction (ADDWoR) comparatively, to get a better understanding of the disease progress without intervention. This longitudinal retrospective study included 217 joints in 165 patients, which were divided into ADDWR group and ADDWoR group based on magnetic resonance imaging (MRI) examination. The joints were assessed quantitatively for disc length and displacement distance at initial and follow-up visits. Disc morphology, which was classified in 5 types, was also evaluated. Paired t-test and Wilcoxon signed rank test were used to assess intra group differences and independent t-test for inter-group differences. Moreover, analysis of covariance was applied to analyze influential factors for changes in disc length and displacement distance. According to our results, discs tended to become shorter, move further forward and distort more seriously in ADDWoR group than in ADDWR group after follow-up. Moreover, discs were prone to become shorter and more anteriorly displaced in teenagers, type I and III morphologies, advanced Wilkes stages, or those with joint effusion. Follow-up period seemed to be not critical. PMID- 27671372 TI - Comparison of The Canary System and DIAGNOdent for the in vitro detection of caries under opaque dental sealants. AB - AIM: The aim of the present study was to investigate the ability of operators using The Canary System and DIAGNOdent to detect natural pit and fissure caries under four commonly-used opaque dental sealants. METHODS: Mixed sound and carious pits/fissures (N = 105) selected from 40 human teeth were randomly assigned (10 teeth/group) to one of four opaque sealant groups (Delton, Embrace WetBond, Helioseal F, UltraSeal XT Plus). Selected pits/fissures sites on occlusal surfaces were scanned with The Canary System and DIAGNOdent, sealed, re-scanned, and subjected to polarized light microscopy to confirm whether the scanned regions were sound or carious. Sensitivities and specificities for each detection method before and after sealant placement were calculated. RESULTS: The Canary System and DIAGNOdent were able to distinguish between sound and carious tissue beneath opaque sealants with an accuracy of 76% and 59%, respectively. CONCLUSIONS: The Canary System can serve as a clinical tool to aid dental professionals to detect and monitor the status of caries lesions and tooth structure underneath sealant. The increased likelihood of false-positive diagnoses with DIAGNOdent due to intrinsic auto-fluorescence of sealant filler and opacifying agents might limit its usefulness as an aid to detect caries underneath opaque sealants. PMID- 27671373 TI - Impaired Spatial Learning is Associated with Disrupted Integrity of the White Matter in Akt3 Knockout Mice. PMID- 27671374 TI - Non-Volatile ReRAM Devices Based on Self-Assembled Multilayers of Modified Graphene Oxide 2D Nanosheets. AB - 2D nanomaterials have been actively utilized in non-volatile resistive switching random access memory (ReRAM) devices due to their high flexibility, 3D-stacking capability, simple structure, transparency, easy fabrication, and low cost. Herein, it demonstrates re-writable, bistable, transparent, and flexible solution processed crossbar ReRAM devices utilizing graphene oxide (GO) based multilayers as active dielectric layers. The devices employ single- or multi-component-based multilayers composed of positively charged GO (N-GO(+) or NS-GO(+)) with/without negatively charged GO(-) using layer-by-layer assembly method, sandwiched between Al bottom and Au top electrodes. The device based on the multi-component active layer Au/[N-GO(+)/GO(-)]n /Al/PES shows higher ON/OFF ratio of ~105 with switching voltage of -1.9 V and higher retention stability (~104 s), whereas the device based on single component (Au/[N-GO(+)]n /Al/PES) shows ~103 ON/OFF ratio at +/-3.5 V switching voltage. The superior ReRAM properties of the multi component-based device are attributed to a higher coating surface roughness. The Au/[N-GO(+)/GO(-)]n /Al/PES device prepared from lower GO concentration (0.01%) exhibits higher ON/OFF ratio (~109 ) at switching voltage of +/-2.0 V. However, better stability is achieved by increasing the concentration from 0.01% to 0.05% of all GO-based solutions. It is found that the devices containing MnO2 in the dielectric layer do not improve the ReRAM performance. PMID- 27671375 TI - Clinical and radiological investigations of mandibular overdentures supported by conventional or mini-dental implants: A 2-year prospective follow-up study. AB - STATEMENT OF PROBLEM: Conventional dental implants are not applicable in the mandibular interforaminal region if bone volume is limited. Mini-dental implants offer an alternative means of supporting mandibular overdentures in a narrow residual ridge, without additional surgery. PURPOSE: The purpose of this nonrandomized clinical trial was to compare the ability of mini-dental implants with that of conventional dental implants in supporting mandibular overdentures during a 2-year clinical follow-up. Bone quality, bone resorption, implant stability, and oral health were assessed radiographically. MATERIAL AND METHODS: A total of 32 participants with edentulism were included. Twenty-two participants (99 implants) received 4 to 5 mini-dental implants (diameter: 1.8-2.4 mm; length: 13-15 mm, study group), and 10 participants (35 implants) received 2 to 4 conventional dental implants (diameter: 3.3-3.7 mm; length: 11-13 mm, control group). The selection of the participants in the study or control group was based on the available bone volume in the mandible. The selection was not randomized. The density of cortical bone thickness was measured in Hounsfield units (HU) from computed tomography data, and patients were followed for 2 years. The participants were examined 3, 6, 12, and 24 months after surgery. Primary stability immediately after the insertion of dental implants (Periotest), secondary stability 6 months after implantation, modified plaque, bleeding on probing indices, and probing depth were measured and analyzed statistically (alpha=.05). RESULTS: The mean HU value 6 months after implantation in the participants who received mini-dental implants was significantly (P=.035) higher (1250 HU) than that in the participants who received conventional dental implants (1100 HU). The probing depths around the conventional dental implants (1.6 and 1.8 mm, respectively) were significantly higher than those around the mini-dental implants (1.3 and 1.2 mm, respectively) 12 and 24 months after surgery, respectively (P<.001). The mean primary and secondary stability values for conventional dental implants were -4.0 and -4.9, respectively. The primary and secondary stability values for the mini-dental implants were -0.3 and -1.4, respectively. The Periotest values of the primary (measured immediately after implant insertion) and secondary implant stabilities (measured 6 months after implant insertion) were significantly higher for the conventional dental implants than for the mini-dental implants (P<.001). CONCLUSIONS: Based on this 2-year clinical trial, patients receiving mini-dental implants had clinical outcomes similar to those of patients receiving conventional dental implants to support overdenture prostheses. PMID- 27671376 TI - Upgrading HepG2 cells with adenoviral vectors that encode drug-metabolizing enzymes: application for drug hepatotoxicity testing. AB - INTRODUCTION: Drug attrition rates due to hepatotoxicity are an important safety issue considered in drug development. The HepG2 hepatoma cell line is currently being used for drug-induced hepatotoxicity evaluations, but its expression of drug-metabolizing enzymes is poor compared with hepatocytes. Different approaches have been proposed to upgrade HepG2 cells for more reliable drug-induced liver injury predictions. Areas covered: We describe the advantages and limitations of HepG2 cells transduced with adenoviral vectors that encode drug-metabolizing enzymes for safety risk assessments of bioactivable compounds. Adenoviral transduction facilitates efficient and controlled delivery of multiple drug metabolizing activities to HepG2 cells at comparable levels to primary human hepatocytes by generating an 'artificial hepatocyte'. Furthermore, adenoviral transduction enables the design of tailored cells expressing particular metabolic capacities. Expert opinion: Upgraded HepG2 cells that recreate known inter individual variations in hepatic CYP and conjugating activities due to both genetic (e.g., polymorphisms) or environmental (e.g., induction, inhibition) factors seems a suitable model to identify bioactivable drug and conduct hepatotoxicity risk assessments. This strategy should enable the generation of customized cells by reproducing human pheno- and genotypic CYP variability to represent a valuable human hepatic cell model to develop new safer drugs and to improve existing predictive toxicity assays. PMID- 27671378 TI - Allitt's legacy. AB - Against a depressing backdrop of rising unemployment, plummeting morale and concern for lower standards of care, the RCN Congress last week heard time and again the pressures nurses are facing at the coal face. PMID- 27671377 TI - Biocompatibility and biodistribution of functionalized carbon nano-onions (f CNOs) in a vertebrate model. AB - Functionalized carbon nano-onions (f-CNOs) are of great interest as platforms for imaging, diagnostic and therapeutic applications due to their high cellular uptake and low cytotoxicity. To date, the toxicological effects of f-CNOs on vertebrates have not been reported. In this study, the possible biological impact of f-CNOs on zebrafish during development is investigated, evaluating different toxicity end-points such as the survival rate, hatching rate, and heart beat rate. Furthermore, a bio-distribution study of boron dipyrromethene (BODIPY) functionalized CNOs in zebrafish larvae is performed by utilizing inverted selective plane illumination microscopy (iSPIM), due to its intrinsic capability of allowing for fast 3D imaging. Our in vivo findings indicate that f-CNOs exhibit no toxicity, good biocompatibility (in the concentration range of 5-100 MUg mL-1) and a homogenous biodistribution in zebrafish larvae. PMID- 27671379 TI - NHS cutbacks alarm Congress. AB - Nurses warned the NHS is 'on the edge of a crisis' as a result of government underfunding, when more than 1,000 RCN members met in Harrogate last week for their annual Congress. PMID- 27671380 TI - Call for an open inquiry on Allitt murders at Grantham. AB - By Jackie O'Byrne & Daniel Allen Nursing unions have joined the parents of children murdered by nurse Beverley Allitt in calling for a full public inquiry into the tragedy. PMID- 27671381 TI - CN training hits crisis in Scotland. AB - The number of Scottish community nurse trainees has plummeted by 80 per cent in the past four years. PMID- 27671382 TI - Community care 'mere lip service'. AB - Community care plan drafters have been accused of paying mere lip service to the principle of putting clients at the forefront of care. PMID- 27671384 TI - More than a thousand nurses gathered in Harrogate last week for the Royal College of Nursing Congress. Daniel Allen, Simon Canning and John Naish report. AB - Health Minister Brian Mawhinney announced at Congress a L1-million package designed to boost nursing, but gave no commitment on nurse prescribing or PREP. PMID- 27671383 TI - Unions outraged by drugs cuts. AB - Nursing unions have condemned as 'outrageous' government plans to consider charging pensioners and children for prescriptions. PMID- 27671385 TI - Revisions expected in maternity care. AB - Far reaching changes in maternity care - with greater emphasis on mothers' wishes - are expected to be unveiled later this year. PMID- 27671386 TI - World news. AB - Russia Millions of doses of vaccines to ward against an outbreak of childhood diseases are being sent to the former Soviet Union under a World Health Organization initiative. PMID- 27671388 TI - ? AB - Bosnia Mentally disturbed victims of the war in Bosnia, and other former Yugoslav states, are to receive help from the World Health Organization. PMID- 27671389 TI - Stop-smoking success linked to practice nurses. AB - Support from practice nurses is a key factor in helping people to quit smoking, a general practice study has found. PMID- 27671390 TI - Inexperienced doctors cause diagnostic errors. AB - Doctors in accident and emergency departments could be sued for negligence if they fail to check a nurse's diagnosis which later proves to be incorrect, a new report says. PMID- 27671391 TI - Study links computers to seizures in children. AB - A national survey to investigate links between computer games and seizures in children was launched last week by the National Society for Epilepsy. PMID- 27671393 TI - Skin gives due to meningococcal illness. AB - Microbiological examination of the skin might be useful in the diagnosis of meningococcal infections, researchers from the Netherlands suggest. PMID- 27671392 TI - Elderly people receive poor mental health care. AB - Older people are ignored by medical services when it comes to their mental health care, it was heard at the charity Council and Care's annual meeting last week. PMID- 27671394 TI - BP and smoking linked to renal disease. AB - An early rise in arterial pressure and smoking are implicated in the development of persistent microalbuminuria in diabetic patients with poor glucose control. PMID- 27671395 TI - US health awareness on the decline? AB - Healthy habits adopted by many Americans seem to be slipping, according to a recent Harris survey. PMID- 27671396 TI - UVA/UVB sunscreen for the ultrasensitive. AB - People with a particular sensitivity to the sun might benefit from using a sunscreen containing both UVA and UVB radiation. PMID- 27671398 TI - In the wake of Allitt. AB - Beverley Allitt will haunt the good name of nursing for a long time to come. The 24-year old nurse, convicted of the murder of four children; and of attempting to murder three others, and harming six more, has given the profession more column inches in the newspapers than years of high quality care could ever do. The tabloids' 'Angel of Death' has entered the annals of nursing history. PMID- 27671397 TI - Hazards of warfarin during pregnancy. AB - Anticoagulation with warfarin during pregnancy is hazardous and maternal coagulation indices do not predict safety in the fetus. PMID- 27671399 TI - Implications for the future. AB - In the wake of the Beverley Allitt case, perhaps it is timely to consider the implications for all nurses involved in the care of children in tertiary, secondary and primary care settings. PMID- 27671400 TI - A dream come true or a nightmare? AB - I would like to share a recent dream with your readers in the hope that someone can offer me an interpretation. PMID- 27671402 TI - ? PMID- 27671401 TI - Bottomley adding insult to injury. AB - After the recent Beverley Allitt case and the subsequent media coverage, I was saddened to hear on the BBC's Six O'clock News on May 17 that members of the public may believe that the training nurses undergo leaves something to be desired. PMID- 27671403 TI - More software for less shekels, please. AB - I welcome the space devoted to demystifying computers and programs through the articles written by Philip Burnard, but am dismayed by his tendency to focus on the more expensive products. PMID- 27671404 TI - No need to feel alone in the private sector. AB - I was surprised to read that Joe Winters considers a move to the private sector by a nurse akin to being 'thrown in at the deep end' (Desperate diaspora, Viewpoint, May 12). PMID- 27671405 TI - Jettison jargon and get back to basics. AB - I must pick up on a point made by Geoffrey Hunt in a news item in the May 12 issue. I agree that the slavish trotting out of self-important jargon such as 'deontology, utilitarianism, beneficence, non-maleficence...' in teaching ethics should be avoided. PMID- 27671406 TI - Converts with get up and go should do so. AB - I recently completed the conversion course to RGN. After a year of hard work, I wonder what it was all for. PMID- 27671407 TI - Information exchange. AB - *We are looking to improve our discharge planning and would be interested to see any paediatric documentation other hospitals are using. PMID- 27671409 TI - New nurses act up. AB - Hi there, health care workers. How are things developing in your new nursing units? Bet there's hardly enough time to attend to the clients with all this quality assurance work and fund-raising for new equipment. I'm sure our unit's Standards of Care would never have been written if Roz and Jeremy hadn't taken some study leave to work on them. PMID- 27671408 TI - Gossip. AB - So the government is considering asking Tesco's and Sainsbury's to build hospitals on the cheap. It is hypermarket hypermania. But what is so crazy about that? It was only a matter of time before the hang 'em and flog 'em and the pile 'em high and flog 'em brigades joined forces. PMID- 27671410 TI - Spiritual Care B Narayanasamy Spiritual Care Quay 66pp L5.50 1-85642-054-X. AB - Spiritual Care: A Practical Guide for Nurses is intended as a resource 'for nurses who want a quick guided introduction to the subject of spirituality and spiritual care' and aims to heighten nurses' awareness of it by focusing on this oft- neglected aspect of care. Particularly pertinent is that over 74 per cent of the UK population belongs to some religious organisation. PMID- 27671411 TI - An Active Retirement N Tuft An Active Retirement Age Concern 14pp L7.95 0-886242 119-5. AB - In one study, people of retirement age were asked how well they adjusted to this new phase of their lives. The response divided two to one in negative terms and revealed that those with positive attitudes were motivated to restructure their lives and continue lifetime hobbies or develop new interests. PMID- 27671412 TI - Health Visiting K Luker J Orr Health Visiting editors Blackwell Scientific 262pp L12.99 0-632-03324-X [Formula: see text]. AB - The danger inherent in reviewing any second edition is that one spends the whole time comparing it with the first edition. I have tried to look at Health Visiting: Towards Community Health Nursing in isolation from the first, but this has been quite difficult as I, among others, used the first edition so extensively during my health visitor training. PMID- 27671413 TI - The Home Office Computer Book The Home Office Computer Book Rimmer S Sybex Inc, Computer Manuals L17.95. AB - This book is not quite what it seems - its title would suggest it is about the ins and outs of working from home. PMID- 27671415 TI - Listings. PMID- 27671414 TI - Computers in General Practice Peckitt R Sigma Press , Computer Manuals L12.95. AB - This is a useful book for anyone in the health profession who is starting to work with computers. PMID- 27671417 TI - Editorial. PMID- 27671416 TI - SMAR1 binds to T(C/G) repeat and inhibits tumor progression by regulating miR-371 373 cluster. AB - Chromatin architecture and dynamics are regulated by various histone and non histone proteins. The matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIP sequencing. The study revealed that SMAR1 binds to T(C/G) repeat and targets genes involved in diverse biological pathways. We observe that SMAR1 binds and targets distinctly different genes based on the availability of p53. Our data suggest that SMAR1 binds and regulates one of the imperative microRNA clusters in cancer and metastasis, miR-371-373. It negatively regulates miR-371-373 transcription as confirmed by SMAR1 overexpression and knockdown studies. Further, deletion studies indicate that a ~200 bp region in the miR-371-373 promoter is necessary for SMAR1 binding and transcriptional repression. Recruitment of HDAC1/mSin3A complex by SMAR1, concomitant with alteration of histone marks results in downregulation of the miRNA cluster. The regulation of miR-371-373 by SMAR1 inhibits breast cancer tumorigenesis and metastasis as determined by in vivo experiments. Overall, our study highlights the binding of SMAR1 to T(C/G) repeat and its role in cancer through miR-371-373. PMID- 27671418 TI - Evaluation of patient wristbands and patient identification process in a training hospital in Turkey. AB - Purpose The purpose of this paper is to evaluate the utilisation of patient wristbands (PWs) and patient identification (PI) process in a training hospital in Ankara, Turkey. Design/methodology/approach This descriptive and cross sectional study was conducted in a training hospital with 640 beds, accreditied by Joint Commission International. The views of 348 patients and 419 hospital personnel on the implementation of patient wristbands and identification process were evaluated. Findings The results indicated that lack of information among patients about the importance of PWs and the misknowledge among staff participants on when, where, and by whom PWs should be put on and verified were the weakest points in this hospital. Research limitations/implications PI process must be strictly implemented according to the standard procedures of patient safety. Both patients and hospital personnel should be trained continuously, and training sessions must be held to increase their awareness about the importance of PWs and identification process. Practical implications Finding new ways and using new methods for increasing knowledge about PI and PWs are necessary. Hospital management should prepare a written PI and PW policy and procedure documents by taking the views of patients and hospital personnel and share these with them. Originality/value This study incorporates the views and attitudes of patients and health care personnel in improving health care quality by increasing awareness about PI and wristbands. PMID- 27671419 TI - Barriers to accurately measuring patients' dietary intake in hospitals using the visual estimation method. AB - Purpose Visual estimation, an easy-to-perform technique, is commonly used in hospitals to assess dietary intake in patients. The authors performed a qualitative study where the authors interviewed nurses and dietitians about their perceptions of barriers to accurately measuring patients' dietary intake in hospitals using the visual estimation method. The paper aims to discuss these issues. Design/methodology/approach Ten dietitians and ten clinical nurses responded to 30-minute individual interviews in Tokyo, Japan, in September 2014. Each interview was conducted using a common protocol of open-ended questions focusing on the challenges of the visual estimation method and barriers to accurately measuring patients' dietary intake as part of their routine work. The tape-recorded interviews were transcribed and analyzed based on grounded theory. Findings Five main categories emerged: hospitals, meals, colleagues, raters, and patients. Various individual barriers such as skill, attitude, knowledge, and others that had not been considered in previous studies also emerged. External barriers that were out of the raters' control, such as shortage of time, human resources, financial ability, and others, emerged from the "hospitals" category. Research limitations/implications Research participants were all females and many of them had less than ten years of experience. Practical implications In addition to standardizing the visual estimation process, medical staff need to overcome various other internal and external barriers to accurate measurements. Originality/value This is the first study to articulate some important barriers that influence reliability and validity when measuring patients' dietary intake by visual estimation methods in typical clinical settings. PMID- 27671420 TI - Dispensing medication refills without counselling. AB - Purpose The purpose of this paper is to assess the safety and efficiency of, and acceptance by, patients for an express refill service (ERS). Design/methodology/approach A pilot uncontrolled, cross-sectional, single-centred study was conducted at the outpatient pharmacy of a tertiary acute care hospital. Under ERS, prescriptions were dispensed without clinical review and counselling for patients refilling prescription medications. Efficiency was assessed by comparing processing times of ERS prescriptions with regular prescriptions. Safety was assessed by independent review of prescriptions by two pharmacists. Patient acceptance was assessed by a survey. Findings ERS reduced processing time of prescriptions by more than 30 per cent compared to the regular fill process. ERS was generally safe for patients, with drug-related problems identified in only one prescription which may have warranted closer monitoring. It was accepted by patients who opted for the service, as 91.4 per cent agreed or strongly agreed that they were satisfied with the service. Research limitations/implications The study was conducted on a small convenience sample of patients in a single centre, with no control group. Practical implications Results showed that ERS was efficient, safe and well-accepted for select patients refilling their prescriptions. This leads to shorter waiting times and greater patient satisfaction. Originality/value This is the first published study that has explored the feasibility of an express prescription refill service. Despite some limitations, this study showed that omitting prospective clinical review and patient counselling for a defined population segment is safe, and can reduce processing time and improve patient satisfaction. PMID- 27671421 TI - Improving patient and staff outcomes using practice development. AB - Purpose The purpose of this paper is to examine the impact of a practice development program, "Essentials of Care" (EOC), on patient and staff outcomes, workplace culture and service delivery. Design/methodology/approach A descriptive study design was used to explore the impact of EOC in a district hospital rehabilitation ward. EOC focuses on embedding a person-centered culture within clinical areas and is structured from practice development methodologies. EOC was implemented in a metropolitan district hospital rehabilitation, older person 20 bed, ward. Findings Two projects were implemented during EOC. These projects led to nine significant patient and staff outcomes for medication and continence care practices. Outcomes included a reduction in older person complaints by 80 percent, pressure injuries by 62 percent, ward multi resistant staphylococcus aureus infection rates by 50 percent, clinical incidents by 22 percent, older person falls by 14 percent (per 1,000 bed days) and nursing sick leave by 10 percent. There was also a 13 percent improvement in the post nursing workplace satisfaction survey. Research limitations/implications This is a single site study and findings may not be suitable for generalizing across ward settings and broader population groups. Originality/value The EOC program led to significant improvements for and in clinical practices, staff satisfaction and ward culture. Specifically, the EOC program also identified significant cost savings and brought together the healthcare team in a cohesive and integrated way not previously experienced by staff. Practice development strategies can champion service quality improvement, optimal patient outcomes and consistency within healthcare. PMID- 27671422 TI - Stakeholders' roles and responsibilities regarding quality of care. AB - Purpose The purpose of this paper is to describe how different stakeholders (society, managers, employees and clients) can together ensure the quality of care. Design/methodology/approach Qualitative data were collected from four focus group interviews conducted in three countries. All interviewees were pursuing a master's degree in social and/or health care management and had begun working in their field after completing their bachelor's degree. The data were analysed using inductive content analysis. Findings The society and managers are responsible for the care system as a whole and must apply system-oriented, rather than sector-oriented, thinking. Employees are responsible for ensuring the continuity of client services in their work, and managers and employees share the responsibility of achieving the organisational goals and quality standards. The clients are responsible for acting as responsible service users and providing the required information to obtain care. Communication was strongly emphasised in the data, and it necessitates cross-professional and organisational boundaries, professional and political boundaries, as well as boundaries between the professional and the client. Research limitations/implications Since the interviewees were all pursuing a master's degree in social and/or health care management, when reflecting on their work experience, they may have also been reflecting what they had learned in university. Practical implications This study emphasises the importance of collaboration and communication between stakeholders in ensuring the quality of care. Unpredictable economies, the ageing population and the ongoing integration and reorganisation of health and social care services in Europe highlight systematic and strategic approach in quality of care. Originality/value This paper claims that communication between different care stakeholders gives a more systematic and coherent framework for the quality of care. Quality of care is a strategic choice and part of the strategic decision making at the societal, political, organisational and managerial levels. PMID- 27671423 TI - The impact of Lean bundles on hospital performance: does size matter? AB - Purpose The purpose of this paper is to study the effect of the implementation of Lean bundles on hospital performance in private hospitals in Jordan and evaluate how much the size of organization can affect the relationship between Lean bundles implementation and hospital performance. Design/methodology/approach The research is considered as quantitative method (descriptive and hypothesis testing). Three statistical techniques were adopted to analyse the data. Structural equation modeling techniques and multi-group analysis were used to examine the research's hypothesis, and to perform the required statistical analysis of the data from the survey. Reliability analysis and confirmatory factor analysis were used to test the construct validity, reliability and measurement loadings that were performed. Findings Lean bundles have been identified as an effective approach that can dramatically improve the organizational performance of private hospitals in Jordan. Main Lean bundles - just in time, human resource management, and total quality management are applicable to large, small and medium hospitals without significant differences in advantages that depend on size. Originality/value According to the researchers' best knowledge, this is the first research that studies the impact of Lean bundles implementation in healthcare sector in Jordan. This research also makes a significant contribution for decision makers in healthcare to increase their awareness of Lean bundles. PMID- 27671424 TI - Healthcare and aging: do European Union countries differ? AB - Purpose The purpose of this paper is to evaluate socio-economic inequalities in the use, accessibility and satisfaction with health services amongst 60-84 year old people from seven European urban communities. Design/methodology/approach Data for this study were collected in 2009. The target population was people aged 60-84 years from Stuttgart (Germany), Athens (Greece), Ancona (Italy), Kaunas (Lithuania), Porto (Portugal), Granada (Spain) and Stockholm (Sweden). The total sample comprised 4,467 respondents with a mean response rate across these countries of 45.2 per cent. Findings The study demonstrated that the majority of respondents had contact with a health care provider within the last 12 months. The highest percentages were reported by respondents from Spain (97.8 per cent) and Portugal (97.7 per cent). The results suggest that 13.0 per cent of respondents had refrained from seeking care services. The highest rates were amongst seniors from Lithuania (24.0 per cent), Germany (16.2 per cent) and Portugal (15.4 per cent). Logistic regression suggests that seniors who refrained from seeking health care was statistically significant associated with those with higher levels of education (odds ratios (OR)=1.21; 95 per cent confidence intervals (CI)=1.01-1.25) and financial strain (OR=1.26; 95 per cent CI=1.16 1.37). Furthermore, the majority of respondents were satisfied with health care services. Originality/value The findings from the "Elder Abuse: a multinational prevalence survey" study indicate the existence of significant variations in use, accessibility and satisfaction with health services by country and for socio economic factors related to organizing and financing of care systems. PMID- 27671425 TI - Health providers' perception of quality of care for neonates in health facilities in a municipality in Southern Ghana. AB - Purpose The purpose of this paper is to assess available human resources for neonatal care and their skills, in order to explore health providers' perceptions of quality of neonatal care in health facilities in Ghana. Design/methodology/approach Data were gathered using qualitative interviews with health providers working in the maternity and paediatric wards and midwives; direct observation; and documentary review at a regional hospital, a municipal hospital and four health centres in a municipality in a region in Southern Ghana. Data were analysed using thematic framework through the process of coding in six phases to create and establish meaningful patterns. Findings The study revealed that health providers were concerned about the number of staff available, their competence and also equipment available for them to work more efficiently. Some essential equipment for neonatal care was either not available or was non functional where it was available, while aseptic procedures were not adhered to. Moreover, personal protective equipment such as facemask, caps, aprons were not used except in the labour wards where staff had to change their footwear before entering. Research limitations/implications Limited number of health providers and facilities used, lack of exploration of parents of neonates' perspective of quality of neonatal care in this study and other settings, including the teaching hospitals. The authors did not examine issues related to the ineffective use of IV cannulation for neonates by nurses as well as referral of neonates. Additionally, the authors did not explore the perspectives of management of the municipal and regional health directorates or policy makers of the Ministry of Health and Ghana Health Service regarding the shortage of staff, inadequate provision of medical equipment and infrastructure. Practical implications This paper suggests the need for policy makers to redirect their attention to the issues that would improve the quality of neonatal health care in health facilities in Ghana and in countries with similar challenges. Social implications The study found that the majority of nursing staff catering for sick newborns were not trained in neonatal nursing. Babies were found sleeping in separate cots but were mixed with older children. The study suggests that babies should be provided with a separate room and not mixed with older babies. Originality/value There seemed to be no defined policy framework for management of neonatal care in the country's health care facilities. The study recommends the adoption of paediatric and neonatal care nursing as a specialty in the curricula of health training institutions. In-service trainings should encompass issues related to management of sick babies, care of preterm babies, neonatal resuscitation and intravenouscannulation, among others. PMID- 27671426 TI - Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity. AB - Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment. PMID- 27671432 TI - Restored to Life. AB - Long-stay psychiatric patients who may have become 'institutionalised' pose the greatest problem to the rehabilitation services-St. Wulstan's Hospital, Malvern, is showing how to overcome the problem. PMID- 27671433 TI - On Finding a Job. AB - Coming out of psychiatric hospital back on to the labour market is often a daunting experience. A man who coped but is critical of the help available suggests where there is room for improvement. PMID- 27671427 TI - Dynamics of Water in Gemini Surfactant-Based Lyotropic Liquid Crystals. AB - The dynamics of water confined to nanometer-sized domains is important in a variety of applications ranging from proton exchange membranes to crowding effects in biophysics. In this work, we study the dynamics of water in gemini surfactant-based lyotropic liquid crystals (LLCs) using molecular dynamics simulations. These systems have well characterized morphologies, for example, hexagonal, gyroid, and lamellar, and the surfaces of the confining regions can be controlled by modifying the headgroup of the surfactants. This allows one to study the effect of topology, functionalization, and interfacial curvature on the dynamics of confined water. Through analysis of the translational diffusion and rotational relaxation, we conclude that the hydration level and resulting confinement length scale is the predominate determiner of the rates of water dynamics, and other effects, namely, surface functionality and curvature, are largely secondary. This novel analysis of the water dynamics in these LLC systems provides an important comparison for previous studies of water dynamics in lipid bilayers and reverse micelles. PMID- 27671434 TI - From Where I Sit: Editorial Comment. PMID- 27671435 TI - Colleagues on the Beat. AB - The police often find themselves cast in the roles of counsellors or social workers by the very nature of their work yet there is hardly any 'mental health' content in their training and other social work agencies seem reluctant to count them as allies. PMID- 27671436 TI - Choose Your Speed. AB - The pace of modern life is often quoted as a factor in mental ill-health although it is difficult to establish a scientific link. All the same, being able to 'pace' your life properly to suit the conditions is an important factor in personal stability. PMID- 27671437 TI - News Review. PMID- 27671438 TI - Letters. PMID- 27671439 TI - Towards Self-Discovery. AB - A woman who regularly takes part in group therapy sessions explains how she came to them and what they mean to her. PMID- 27671440 TI - Crabbit Old Woman. AB - A poem about old age and its reflections of youth said to have been found among the effects of an old woman after her death in a geriatric hospital. PMID- 27671441 TI - Combating Social Handicap. AB - Report on a group of parents with handicapped children who came together to organise activities to overcome their childrens' lack of social education. PMID- 27671442 TI - Scan. AB - A personal view of the social services. PMID- 27671443 TI - Kept in the Background. AB - An ex-patient draws on his own experience to suggest how life in mental hospital could be made more beneficial in simple ways and expresses reservations about the acceptance of patients back into the community. PMID- 27671444 TI - Observation of unusual topological surface states in half-Heusler compounds LnPtBi (Ln=Lu, Y). AB - Topological quantum materials represent a new class of matter with both exotic physical phenomena and novel application potentials. Many Heusler compounds, which exhibit rich emergent properties such as unusual magnetism, superconductivity and heavy fermion behaviour, have been predicted to host non trivial topological electronic structures. The coexistence of topological order and other unusual properties makes Heusler materials ideal platform to search for new topological quantum phases (such as quantum anomalous Hall insulator and topological superconductor). By carrying out angle-resolved photoemission spectroscopy and ab initio calculations on rare-earth half-Heusler compounds LnPtBi (Ln=Lu, Y), we directly observe the unusual topological surface states on these materials, establishing them as first members with non-trivial topological electronic structure in this class of materials. Moreover, as LnPtBi compounds are non-centrosymmetric superconductors, our discovery further highlights them as promising candidates of topological superconductors. PMID- 27671445 TI - Adipocyte-derived microvesicles from obese mice induce M1 macrophage phenotype through secreted miR-155. AB - The pro-inflammatory profile of M1 macrophage accumulation in adipose tissue is a central event leading to the metabolic complications of obesity. However, the mechanisms by which M1 macrophages are enriched in adipose tissue during weight gain remain incompletely understood. Here, we investigated the effects of adipocyte-derived microvesicles (ADM) on modulating macrophage phenotype in mice and explored the involved molecular signalling pathways. We found that, compared with ADM from lean mice (SD ADM), ADM from obese mice (HFD ADM) significantly enhanced M1 marker expression. The quantitative RT-PCR assay demonstrated that miR-155 was upregulated in both HFD ADM and HFD ADM-treated macrophages. By depleting miR-155 expression in HFD ADM and increasing miR-155 level in SD ADM, we further illustrated that miR-155 in ADM-induced M1 macrophage polarization. Functionally, in contrast to SD ADM, HFD ADM significantly decreased the protein level of SOCS1, a proven miR-155 target, leading to activation of STAT1, and suppression of STAT6 signalling; these effects were reversed by silencing miR-155 in HFD ADM. Furthermore, the supernatant of bone marrow-derived macrophages pre stimulated with miR-155-bearing ADM interfered with insulin signalling and insulin-induced glucose uptake in adipocytes. Collectively, these results provide the first evidence that M1 macrophage polarization can be mediated by miR-155 bearing ADM, which reciprocally regulates insulin signalling and glucose uptake in adipocytes. Our study reveals a novel mechanism through which obesity induces an imbalance in the M1-to-M2 macrophage ratio in adipose tissue, thus causing chronic inflammation and local insulin resistance. PMID- 27671447 TI - Psychological Distress Among Older Prisoners: Associations With Health, Health Care Utilization, and the Prison Environment. AB - Physical and functional health issues among older prisoners may be difficult to address in an environment designed for younger inmates. This article investigates the relationships between older prisoners' health, their experiences of the prison environment and health services, and their levels of psychological distress. One hundred and seventy-three older prisoners (aged 50 years and older) from eight Australian prisons were interviewed using the Kessler Psychological Distress Scale, with additional information collected from prisoner interviews and correctional health files. Distress scores were significantly associated with measures of physical health, functional independence, and health care utilization. However, a hierarchical regression analysis determined that physical difficulties in the prison environment and issues accessing prison health care explained a significant proportion of the variation in older prisoners' distress scores. PMID- 27671446 TI - Characterization of aerosols containing Legionella generated upon nebulization. AB - Legionella pneumophila is, by far, the species most frequently associated with Legionnaires' disease (LD). Human infection occurs almost exclusively by aerosol inhalation which places the bacteria in juxtaposition with alveolar macrophages. LD risk management is based on controlling water quality by applying standardized procedures. However, to gain a better understanding of the real risk of exposure, there is a need (i) to investigate under which conditions Legionella may be aerosolized and (ii) to quantify bacterial deposition into the respiratory tract upon nebulization. In this study, we used an original experimental set-up that enables the generation of aerosol particles containing L. pneumophila under various conditions. Using flow cytometry in combination with qPCR and culture, we determined (i) the size of the aerosols and (ii) the concentration of viable Legionella forms that may reach the thoracic region. We determined that the 0.26 2.5 MUm aerosol size range represents 7% of initial bacterial suspension. Among the viable forms, 0.7% of initial viable bacterial suspension may reach the pulmonary alveoli. In conclusion, these deposition profiles can be used to standardize the size of inoculum injected in any type of respiratory tract model to obtain new insights into the dose response for LD. PMID- 27671448 TI - Emergency Endovascular Interventions for Ruptured Descending Thoracic Aortic Aneurysm. AB - BACKGROUND: Ruptured descending thoracic aortic aneurysm (rDAA) is a rare but devastating condition. Open aortic surgery which uses cardiopulmonary bypass is associated with a high mortality. Thoracic endovascular aortic repair (TEVAR) is a less-invasive approach for which it remains unclear whether outcomes are superior or equivalent to open aortic surgery. In this study, we report our early and midterm outcomes with TEVAR for rDAA. METHODS: This is an observational, retrospective, single-center study which included patients with rDAA and treated by TEVAR. The main objective was the 30-day in-hospital mortality. Secondary end points were 30-day in-hospital morbidity, 2-year mortality, and technical problems encountered during procedures. RESULTS: Twenty-five patients were included: 14 men and 11 women with a median age of 76 years (69-82 years). Thirty day in-hospital mortality rate was 36% (95% confidence interval [CI], 20.6-57.9; n = 9), and the 2-year mortality rate was 44% (95% CI, 27.94-66.72; n = 11). Fifteen patients (60%) presented at least 1 major complication, and 8 of those patients had a second surgery because of it. There were 9 technical problems encountered that required additional open procedures to successfully deploy the aortic stent graft: lack of vascular access in 2 cases (8%), short proximal neck in 3 cases (12%), and short distal neck in 4 cases (16%). CONCLUSIONS: Mortality and morbidity remain high in patients treated for rDAA by TEVAR. Nonetheless, TEVAR remains an interesting alternative to open aortic surgery especially for older patients with a poor general health and functional status. PMID- 27671449 TI - Sarcoidosis-Associated Aortoesophageal Fistula-Multistage Interdisciplinary Surgical Therapy for a Rare and Life-Threatening Condition. AB - Aortoesophageal fistulas (AEFs) are rare and life-threatening conditions. Till date, an association between an AEF and sarcoidosis has not been reported yet. The aim of this report is to demonstrate a case of AEF secondary to sarcoidosis and its multistage interdisciplinary surgical therapy. A 66-year-old male was diagnosed with sarcoidosis in 2014. He has been treated with glucocorticoids since then and no severe health restrictions due to the disease have occurred. In December 2015, the patient presented with acute thoracic pain and hematemesis: an esophagogastroscopy revealed an AEF. First, stent-graft implantation in the thoracic aorta was urgently performed as a "bridging" procedure. Second, esophagectomy and local debridement were performed, followed by explantation of the stent graft and reconstruction by means of xenograft replacement of the stented aorta in a third operation. Finally, retrosternal gastric pull-up was performed in a fourth operative procedure. Sixteen days after the last operation the patient could be discharged to a rehabilitation clinic. Follow-up is uneventful so far; the antibiotic therapy was stopped at the time of hospital discharge. The pathogenesis of sarcoidosis, a rare autoimmunological disease, has not been completely clarified yet. The diagnosis relies on clinical symptoms and radiological as well as histopathological findings. Many cases of sarcoidosis show spontaneous regression, but severe complications may occur. While tracheoesophageal fistulas have been described in the literature, AEFs related to sarcoidosis have not been mentioned yet. Despite surgical and antibiotic treatment, the morbidity and mortality rates of AEF are high. Because the endovascular treatment has been established for emergency procedures of the aorta, it is considered as an appropriate first-line "bridging" treatment option. To achieve good long-term results, surgical treatment has to involve esophagectomy with secondary reconstruction of the upper gastrointestinal tract, as well as open aortic replacement using xenograft or homograft material. Sarcoidosis may lead to AEF as demonstrated in this case. Successful treatment can be realized by a multistage interdisciplinary surgical approach. PMID- 27671450 TI - Repair of Chronic Aneurysmal Aortic Dissection Using a Stent Graft and an Amplatzer(r) Vascular Plug: A Case Study. AB - We report a case in which a stent graft and an Amplatzer(r) vascular plug (AVP) were effective for the treatment of chronic aneurysmal aortic dissection. The patient was a 52-year-old man. At 45 years of age, he developed acute aortic dissection, for which he underwent surgery 4 times with prosthetic graft replacement in the abdominal aorta, descending thoracic, ascending aorta (without neck branch reconstruction), and thoracoabdominal aorta with the reconstruction of the celiac, superior mesenteric, and bilateral renal arteries. At the time of thoracoabdominal aortic surgery, strong adhesion was evident, particularly in the thoracoabdominal area. The adhesion was dissected in a part of the chest, and prosthetic graft replacement was performed the following day. Subsequently, the dissection of the residual distal aortic arch enlarged, and the patient was examined at our hospital. Computed tomography (CT) revealed a small intimal tear at the site of anastomosis distal to the graft in the ascending aorta and a large intimal tear in the descending thoracic aorta with a maximum diameter of 67 mm. Furthermore, open repair by prosthetic graft replacement seemed difficult; therefore, treatment with stent grafting was considered. Because the prosthetic graft in the abdomen was extremely tortuous, stent-graft insertion via the femoral artery seemed to be impossible. The planned treatment involved the placement of a thoracic stent graft using the chimney technique which included reconstruction of the brachiocephalic artery and left common carotid arteries using chimney stent graft and coverage of the left subclavian artery. The thoracic stent graft was planned to be inserted via the abdominal prosthetic graft site because the abdominal prosthetic graft was crooked and was located close to the body surface. However, a small intimal tear distal to the graft in the ascending aorta which had not been revealed by intraoperative aortography was detected by the selective angiography, and closure with an AVP was attempted for this. The site was successfully closed using an AVP with a wire passing through the tear and into the false lumen. Thereafter, the large tear in the descending thoracic aorta was closed using a stent graft. The patient made good postoperative progress without evidence of paraplegia, and complete thrombosis of the false lumen was confirmed by postoperative CT. CT at 1 year after thoracic endovascular aneurysm repair (TEVAR) showed complete thrombosis of false lumen and aneurysm shrinkage. PMID- 27671451 TI - Is Multilayer Bare Stent Safe or Effective for the Treatment of Aortic Aneurysms? A Meta-analysis with Early and Mid-term Outcomes. AB - BACKGROUND: As a novel endovascular treatment, multilayer bare stent implantation remains controversial. This study evaluated the safety and efficacy of multilayer bare stent-based endovascular treatment applied in aortic aneurysms in the reported literature. METHODS: Articles regarding multilayer bare stent-based endovascular treatment published before and during February 2016 were obtained by searching PubMed, EMBASE, Wiley Online Library, and Web of Science. R software was employed for a meta-analysis. RESULTS: Five studies including 154 patients satisfied the inclusion criteria. The mean follow-up was 12.7 (8-22.1) months. The rate of aneurysm exclusion was 76.1%. The rate of aneurysm shrinkage and enlargement was 14.1% and 12.5%, respectively. The patency rate of branch vessels was 98.4%. The overall rate of aneurysm rupture was almost 0%. The 30-day postoperative and 1-year aneurysm-related mortality were 0% and 1.7%, respectively. Technical success was achieved in all patients. Only 6.7% of the patients needed reintervention. About 1.9% of the patients suffered endoleak. CONCLUSIONS: Our study indicates that treatment of aneurysms with multilayer bare stents is safe with high technical success rates and low incidence of complications. However, the low rates of aneurysm exclusion are not negligible. Due to the limitations of the existing studies, we only suggest its use for aortic aneurysms with branch vessels if the standard techniques are contraindicated. PMID- 27671452 TI - Radial Artery Compression with Threatened Transection: Catfish Injury in a Pediatric Patient. AB - Marine animal injuries are rare causes of emergency room visits and vascular injuries worldwide. Penetrating injuries from marine animals risk damage to vasculature, and physicians must be alert to such possibilities. We report a 7 year-old boy with penetrating trauma and retained foreign body in the forearm from a catfish injury. Initial imaging suggested transection of the radial artery, but on exposure in a controlled setting the foreign body was found to compress the artery without any vascular injury. No vascular repair was needed after foreign body removal. PMID- 27671453 TI - Percutaneous Treatment of Multiple Recurrent Thromboembolization from a Descending Thoracic Aortic Intimal Sarcoma. AB - Aortic intimal sarcomas are rare tumors that may result in distal embolic ischemia. Here, we present a patient who presented with crescendo lower extremity and mesenteric ischemic events from malignant macroembolism. Management with percutaneous pharmacomechanical thromboembolectomy enabled restoration of distal perfusion and minimally invasive collection of tumor sample to confirm the suspected diagnosis of aortic sarcoma. The patient underwent definitive aortectomy and reconstruction and is recovering well. PMID- 27671454 TI - Outcomes of Left Subclavian Artery Transposition for Hybrid Aortic Arch Debranching. AB - BACKGROUND: The aim of this study was to evaluate outcomes of left subclavian artery (LSA) revascularization for hybrid aortic arch debranching. METHODS: Between 1998 and 2015, 68 patients (41 men; mean age, 67 +/- 16 years) underwent thoracic endovascular aortic repair (TEVAR) with LSA coverage, 19.2% (n = 13) were never revascularized, and the remaining patients underwent LSA revascularization (n = 55; 80.8%). Revascularization was achieved by LSA-carotid transposition via a medial approach in 81.8% (n = 45) and a lateral approach in 18.2% (n = 10). The indication for TEVAR was aneurysmal disease in 30.9% (n = 17), dissection in 29% (n = 16; acute, n = 5), traumatic aortic injury in 21.8% (n = 12), pseudoaneurysm in 10.9% (n = 6), aortobronchial fistula in 5.5% (n = 3), and penetrating atherosclerotic ulcer in 1.9% (n = 1). Elective cases accounted for 52.7% (n = 29). Follow-up computed tomography scans were performed at 1 week, 3 and 6 months, and annually thereafter. RESULTS: LSA revascularization was achieved in all the cases. Thirty-day mortality rate was 12.7%. Thirty-day mortality related to LSA revascularization was 0%. No patient suffered a stroke. Vocal cord paralysis was detected in 7.2% of patients (n = 4). Hematoma requiring surgical drainage was observed in 3.6% of patients (n = 2). Lymph leak requiring revision surgery was observed in 1.8% of patients (n = 1). Phrenic nerve palsy was not observed. The local complication rate was significantly higher (P = 0.03) in patients with LSA transposition via a lateral approach (20%; n = 2) when compared to patients with LSA revascularization via a medial approach (11.1%; n = 5). After a mean follow-up of 31.5 months (range, 2 171 months), the patency of the LSA revascularization was maintained in all patients. CONCLUSIONS: During TEVAR, when LSA coverage is required, LSA revascularization is a durable procedure associated with a low morbidity rate. LSA transposition via a medial approach would appear to be associated with significantly fewer complications. PMID- 27671455 TI - Color Doppler Ultrasound with Superb Microvascular Imaging Compared to Contrast enhanced Ultrasound and Computed Tomography Angiography to Identify and Classify Endoleaks in Patients Undergoing EVAR. AB - BACKGROUND: The aim of the study was to evaluate the diagnostic effectiveness of color Doppler ultrasound (CDUS) with superb microvascular imaging (SMI) compared to contrast-enhanced ultrasound (CEUS), computed tomography (CT) multislice angiography (64 slices), and angiography required for therapeutic reasons, for follow-up after endovascular aneurysm repair (EVAR). METHODS: From March 2014 to May 2015, 57 patients treated with EVAR were evaluated with CT, CEUS, CDUS, SMI, and angiography in cases requiring treatment. Evaluation included sac diameter, stent-graft integrity, identification, and classification of endoleaks. Sensitivity, specificity, accuracy, and negative and positive predictive values were evaluated for each modality of endoleak identification. RESULTS: Eight endoleaks (16.3%), all type II, were documented. Sensitivity of CT, CEUS, CDUS and SMI was 88%, 100%, 63%, and 75%, respectively. Specificity of CT, CEUS, CDUS, and SMI was 100%, 100%, 96%, and 98%, respectively With SMI, CDUS sensitivity significantly increased, whereas specificity did not register great differences. CONCLUSIONS: SMI was more accurate than CDUS but less accurate than CEUS and CT to identify endoleaks after EVAR. SMI could be concretely used in the follow-up phase to increase CDUS accuracy especially in patients who cannot be studied with CEUS or CT. PMID- 27671456 TI - Comparison of Systemic Thrombolysis Versus Indirect Thrombolysis via the Superior Mesenteric Artery in Patients with Acute Portal Vein Thrombosis. AB - BACKGROUND: The aim of this study was to evaluate the safety and efficacy of indirect thrombolysis via the superior mesenteric artery (SMA) in patients with acute portal vein thrombosis. METHODS: Over 10 years, we studied the safety and efficacy of indirect thrombolysis via the SMA in 34 patients with acute portal vein thrombosis. Eighteen patients were categorized as the systemic thrombolysis (ST) group and 16 as the catheter thrombolysis (CT) group. The ST group was administered low-molecular-weight heparin, and patients in the CT group received catheter thrombolysis. Clinical data, such as comorbidities, laboratory test results, therapeutic methods, and prognosis, were recorded. All the patients underwent a routine clinical follow-up that was performed by inpatient examinations or outpatient visits at a mean follow-up time of 34 months. RESULTS: The thrombus score was significantly higher in the ST group (3.67 +/- 1.19) than in the CT group (2.38 +/- 0.62) after 2 weeks of treatment (P < 0.05). The average period of symptom alleviated was longer in the ST group (3.29 +/- 1.59 days) than in the CT group (2.07 +/- 0.73 days, P < 0.05). Five patients (4 in the ST group and 1 in the CT group) underwent a laparotomy because of peritonitis after thrombolysis for 24 hr. One patient died of a malignant tumor after 18 months. CONCLUSIONS: Indirect thrombolysis via the SMA is safer and more effective for patients with portal vein thrombosis compared with systemic thrombolysis. PMID- 27671457 TI - Anaphylactic Reaction during Implantation of Ovation Abdominal Stent Graft in Patients with Abdominal Aortic Aneurysm. AB - The Ovation Abdominal Stent Graft System is a trimodular endoprosthesis planned to overcome the limitations of currently available stent grafts, allowing complex iliac and femoral access and providing a proximal seal in challenge infrarenal neck morphology. The proximal sealing is achieved by means of a network of inflatable rings filled with low-viscosity radiopaque polyethylene glycol-based polymer during stent-graft deployment. The leakage of polymer outside the channel to fill the rings into the vascular system may induce an hypersensitivity reaction and anaphylactic shock. We report a case of anaphylactic reaction during Ovation Abdominal Stent Graft System implantation. The endovascular procedure was successfully concluded. PMID- 27671458 TI - Impact of Integrated Vascular Residencies on Academic Productivity within Vascular Surgery Divisions. AB - BACKGROUND: Changing training paradigms in vascular surgery have been introduced to reduce overall training time. Herein, we sought to examine how shortened training for vascular surgeons may have influenced overall divisional academic productivity. METHODS: Faculty from the top 55 surgery departments were identified according to National Institutes of Health (NIH) funding. Academic metrics of 315 vascular surgery, 1,132 general surgery, and 2,403 other surgical specialties faculty were examined using institutional Web sites, Scopus, and NIH Research Portfolio Online Reporting Tools from September 1, 2014, to January 31, 2015. Individual-level and aggregate numbers of publications, citations, and NIH funding were determined. RESULTS: The mean size of the vascular divisions was 5 faculty. There was no correlation between department size and academic productivity of individual faculty members (R2 = 0.68, P = 0.2). Overall percentage of vascular surgery faculty with current or former NIH funding was 20%, of which 10.8% had major NIH grants (R01/U01/P01). Vascular surgery faculty associated with integrated vascular training programs demonstrated significantly greater academic productivity. Publications and citations were higher for vascular surgery faculty from institutions with both integrated and traditional training programs (48 of 1,051) compared to those from programs with integrated training alone (37 of 485) or traditional fellowships alone (26 of 439; P < 0.05). CONCLUSIONS: In this retrospective examination, academic productivity was improved within vascular surgery divisions with integrated training programs or both program types. These data suggest that the earlier specialization of integrated residencies in addition to increasing dedicated vascular training time may actually help promote research within the field of vascular surgery. PMID- 27671459 TI - Prospective Randomized Study of Ultrasound-Guided Foam Sclerotherapy Combined with Great Saphenous Vein High Ligation in the Treatment of Severe Lower Extremity Varicosis. AB - BACKGROUND: To evaluate the effect of ultrasound-guided foam sclerotherapy (UGFS) in a single session combined with great saphenous vein (GSV) high ligation for severe lower extremity varicosis classified as C4-C6, compared with GSV stripping plus multistab avulsion or transilluminated powered phlebectomy (TIPP). METHODS: From January 2012 to December 2014, 177 patients with primary GSV insufficiency, classified as C4-C6, were randomized into the UGFS group or the control group. The UGFS group was managed by GSV high ligation and foam sclerotherapy in one session under the surveillance of ultrasonography, whereas the control group received GSV high ligation and stripping combined with multistab avulsion or TIPP. The patients were followed up at 1, 6, and 12 months after treatment. Outcome assessments included reflux recurrence rate, procedure-related adverse events, hemodynamic parameters, revised Venous Clinical Severity Score (VCSS), and Aberdeen Varicose Vein Questionnaire (AVVQ) score. The medical cost and operating time of the 2 groups were also compared. RESULTS: In total, 73 patients received UGFS, whereas 90 patients underwent traditional surgery. Sixty-five patients in the UGFS group (89.0%) and 74 patients in the control group (82.2%) completed the follow-up. At the end of 12 months, the cumulative reflux recurrence rate was 13.8% in the UGFS group and 13.5% in the control group (P = 0.955). In the UGFS and control groups, minor complications (27.7% vs. 21.6%, P = 0.406) and major complications (3.1% vs. 2.7%, P = 0.895) were not significantly different. Compared with baseline values, obvious improvements of the venous filling index, VCSS, and AVVQ scores after treatment were confirmed in both groups (P < 0.001). The average operating and recovery times were much shorter (38.3 vs. 81.2 min, 5.4 vs. 9.6 days, P < 0.001, respectively), and the average hospital cost was much lower ($853 vs. $1,575, P < 0.001) in the UGFS group than in the control group. The patient satisfaction rate reached 92.3% in the UGFS group and 89.2% in the control group 12 months after operation (P = 0.270). CONCLUSIONS: Our outcomes indicated that UGFS combined with GSV high ligation was safe and effective for severe lower extremity varicosis. PMID- 27671460 TI - Carbon Dioxide as Contrast Medium to Guide Endovascular Aortic Aneurysm Repair. AB - BACKGROUND: Iodine contrast medium (ICM) is considered to be gold standard in endovascular procedures, but its nephrotoxicity and hypersensitivity limit the widespread use. Carbon dioxide (CO2) is considered as an alternative for endovascular procedures in patients with contraindication to ICM. However, no studies have compared the outcomes of endovascular aneurysm repair (EVAR) performed with ICM or CO2 among patients with no contraindication to ICM. METHODS: From May 2012 to April 2014, 36 patients with abdominal aortic aneurysms underwent EVAR in a prospective, randomized, and controlled study. Patients were randomized into 2 groups, CO2 or ICM group. RESULTS: We were able to perform the proposed procedures in all patients in this study. There were no conversions to open surgery and no CO2-related complications. Endovascular material costs, duration of surgery, and time of fluoroscopy were similar between groups, and the cost of the contrast media was smaller in the CO2 group than in the ICM group. Among CO2 group procedures, 62.5% of the patients needed ICM complementary use. CONCLUSIONS: The use of CO2 as a contrast medium for EVAR is an alternative in patients with no restriction for ICM, with similar outcomes when compared to ICM, regarding duration of surgery, duration of fluoroscopy, and endovascular material costs. Using CO2, there were no changes in creatinine clearance and no risk of hypersensitivity reactions; moreover, there was a reduction in contrast-related costs for EVAR procedures. However, in our study, additional use of ICM to visualize the internal iliac artery was needed in most procedures. PMID- 27671461 TI - Hepatitis E in Norway: seroprevalence in humans and swine. AB - In Norway, no published data on seroprevalence of hepatitis E virus (HEV) in humans and swine exists. Serum samples from blood donors, veterinarians, swine farm workers and swine were analysed by ELISA to estimate the seroprevalence of HEV in Norway and to investigate the association between direct contact with swine and HEV seroprevalence in humans. The seroprevalence of HEV IgG antibodies was 30% (24/79) in farm workers, 13% (21/163) in veterinarians, 14% (162/1200) in blood donors and 90% (137/153) in swine. Our results show a high seroprevalence of HEV in humans and swine in Norway. HEV seroprevalence in farm workers and blood donors increased with age, and veterinarians working with swine were twice as likely to be HEV seropositive compared to other veterinarians. High HEV seroprevalence in farm workers and veterinarians working with swine support previous reports suggesting swine as a reservoir for HEV infections in humans in Europe. PMID- 27671462 TI - Development of long-term antimicrobial poly(methyl methacrylate) by incorporating mesoporous silica nanocarriers. AB - OBJECTIVE: Poly(methyl methacrylate) (PMMA) used as removable denture bases or orthodontic appliances has relatively poor antimicrobial properties, which accelerate oral infection and induce unfavorable odors. Mesoporous silica nanoparticles (MSNs) have been highlighted as a potential additive to overcome this issue because of their drug-loading capacity. Here, we present the long-term antimicrobial effect of MSN-incorporated PMMA with drug-loading capacity. METHODS: After the MSNs were characterized, MSN incorporation into chemically activated PMMA (0.5, 1, 2.5 or 5wt%) relative to the methyl methacrylate powder by mass was fabricated into a rectangular specimen (1.4*3.0*19.0mm) for a 3-point flexural test at a speed of 1mm/min or a disk (?=11.5mm and d=1.5mm) for investigation of its antimicrobial effects. RESULTS: A typical spherical morphology with a well-ordered mesoporous structure of the MSNs was visualized and is beneficial for loading drugs and combining in matrixes. Among the tested levels of MSN incorporation in PMMA (0.5, 1, 2.5 or 5wt%), only 5wt% decreased the flexural strength (p<0.05), whereas the flexural modulus was not significantly decreased (p>0.05). The surface roughness and surface energy were increased with 2.5wt% or 5wt% incorporation. An anti-adherent effect against Candida albicans and Streptococcus oralis after 1h of attachment was only observed with 2.5 and 5wt% incorporation compared to a lack of MSNs (p<0.05). A long-term antimicrobial effect was observed for 2 weeks with 2.5wt% MSN incorporated PMMA when amphotericin B was loaded into the MSNs on the PMMA surface. SIGNIFICANCE: The long-term antimicrobial performance after loading amphotericin B into the MSN-incorporated PMMA suggests the potential clinical usefulness of MSN-incorporated PMMA resin. PMID- 27671463 TI - Interaction between LPS and a dental resin monomer on cell viability in mouse macrophages. AB - OBJECTIVE: Lipopolysaccharide (LPS) from cariogenic microorganisms and resin monomers like HEMA (2-hydroxyethyl methacrylate) included in dentin adhesive are present in a clinical situation in deep dentinal cavity preparations. Here, cell survival, expression of proteins related to redox homeostasis, and viability of mouse macrophages exposed to LPS and HEMA were analyzed with respect to the influence of oxidative stress. METHODS: Cell survival of RAW264.7 mouse macrophages was determined using a crystal violet assay, protein expression was detected by Western blotting, and HEMA- or LPS-induced apoptosis (cell viability) was analyzed by flow cytometry. Cells were exposed to HEMA (0-8mM), LPS (0.1MUg/ml) or combinations of both substances for 24h. The influence of mitogen activated protein kinases (MAPK) was analyzed using the specific inhibitors PD98059 (ERK1/2), SB203580 (p38) or SP600125 (JNK), and oxidative stress was identified by the antioxidant N-acetylcysteine (NAC). RESULTS: Cell survival was reduced by HEMA. LPS, however, increased cell survival from 29% in cultures exposed to 8mM HEMA, to 46% in cultures co-exposed to 8mM HEMA/LPS. Notably, LPS induced apoptosis was neutralized by 4-6mM HEMA but apoptosis caused by 8mM HEMA was counteracted by LPS. Expression of NOS (nitric oxide synthase), p47phox and p67phox subunits of NADPH oxidase, catalase or heme oxygenase (HO-1) was associated with HEMA- or LPS-induced apoptosis. While no influence of MAPK was detected, NAC inhibited cytotoxic effects of HEMA. SIGNIFICANCE: HEMA- and LPS triggered pathways may induce apoptosis and interfere with physiological tissue responses as a result of the differential formation of oxidative stress. PMID- 27671464 TI - Evaluation of monomer leaching from a resin cement through dentin by a novel model. AB - OBJECTIVE: To evaluate the elution of HEMA, BPA, UDMA and BisGMA from a conventional resin cement (Multilink Automix(r), Ivoclar Vivadent) through human dentin, under constant positive pulpal pressure. METHODS: Ten human dentin disks (n=10) were adjusted in a new testing device and transparent glass slabs were luted with Multilink Automix(r) resin cement, following manufacturer's instructions, under a steady pressure of 25N. The device was filled with Ringer's solution. At 5min, 20min, 1h, 2h, 21h, 3 days, 7 days, 10days and 21days time intervals, the whole eluate was retrieved from each one of the ten specimens and then, the specimens were refilled with fresh Ringer's solution. The eluates were analyzed by High Performance Liquid Chromatography (HPLC). RESULTS: HEMA was detected in the eluate of all of the specimens, from 5min until 10 days. At four of the specimens, HEMA was also detected in the 21days eluate at very low concentrations. BPA, UDMA and BisGMA were not detected at any eluate. An unknown compound was also detected at 4.4min. SIGNIFICANCE: The concentrations of HEMA that enabled to diffuse from Multilink Automix(r) cement in an aqueous solution, through a dentin barrier, did not reach toxic levels and BPA, UDMA and BisGMA were not detected at all. PMID- 27671465 TI - Porcelain bonding to novel Co-Cr alloys: Influence of interfacial reactions on phase stability, plasticity and adhesion. AB - OBJECTIVE: The objective of the present study was to determine the hardness and adhesion strength at the porcelain to alloy interface. METHODS: 15 bi-layer porcelain veneered Co-Cr specimens of each alloy group [cast, powder metallurgy (PM), CAD/CAM(CC)] were manufactured. 12 bi-layered specimens were tested using four-point bend strain energy release rate adhesion test. One before and after porcelain firing specimen of each alloy group were nano-indented at the bulk and metal-porcelain interface to determine the mechanical properties. Electron backscatter diffraction was used to determine the microstructure and phase of the indented areas. RESULTS: The results obtained from the four-point bend strain energy release rate test indicated highest adhesion energy of 92.15J/m2 observed in the CC produced Co-Cr alloy. This was followed by the PM alloy with an adhesion energy of 62.24J/m2 and cast alloy with an adhesion energy of 42.83J/m2. All comparisons of adhesion energy between the three alloys were found to be statistically significant (p<.05). Nano-indentation test indicated higher hardness values of 4.6-6.1GPa at the metal-porcelain interface compared to the bulk, which had hardness values of 3.1-3.9GPa. SIGNIFICANCE: The adhesion of the alloy to porcelain was found to be inversely related to the hardness of the interfacial layer at the alloy surface. Lower interfacial hardness was found to be accompanied with higher adhesion energy due to the additional plastic energy consumed during crack propagation along the more ductile interface region of the alloy. PMID- 27671466 TI - Fatigue behavior of resin-modified monolithic CAD-CAM RNC crowns and endocrowns. AB - OBJECTIVE: To evaluate the influence of different types of modifications with resin on fatigue resistance and failure behavior of CAD-CAM resin nano ceramic (RNC) restorations for maxillary first premolars. METHODS: Sixty standardized resin composite root dies received CAD-CAM RNC endocrowns (n=30) and crowns (n=30) (Lava Ultimate, 3M Espe). Restorations were divided into six groups: full anatomic endocrowns (group A) and crowns (group D), buccal resin veneered endocrowns (group B) and crowns (group E) and buccal resin veneered endocrowns (group C) and crowns (group F) with a central groove resin filling. A nano-hybrid resin composite was used to veneer the restorations (Filtek Supreme, 3M Espe). All specimens were first submitted to thermo-mechanical cyclic loading (1.7Hz, 49N, 600000 cycles, 1500 thermo-cycles) and then submitted to cyclic isometric stepwise loading (5Hz) until completion of 105000 cycles or failure after 5000 cycles at 200N, followed by 20000 cycles at 400N, 600N, 800N, 1000N and 1200N. In case of fracture, fragments were analyzed using SEM and modes of failure were determined. Results were statistically analyzed by Kaplan-Meier life survival analysis and log rank test (p=0.05). RESULTS: The differences in survival between groups were not statistically significant, except between groups D and F (p=0.039). Endocrowns fractured predominantly with a mesio-distal wedge-opening fracture (82%). Partial cusp fractures were observed above all in crowns (70%). Analysis of the fractured specimens revealed that the origin of the fracture was mainly at the occlusal contact points of the stepwise loading. SIGNIFICANCE: Veneering of CAD-CAM RNC restorations has no influence on their fatigue resistance except when monolithic crowns are modified on their occlusal central groove. PMID- 27671467 TI - New acid BisGMA analogs for dental adhesive applications with antimicrobial activity. AB - OBJECTIVE: To achieve bisphenol A glycerolate dimethacrylate (BisGMA) analogs with reduced viscosity to be used in the formulation of dental adhesives containing biocidal components. METHODS: A series of low-viscosity BisGMA derivatives (eta: 39-12Pas) modified with 30, 60 and, respectively 80mol% carboxylic acid units were synthesized and characterized. Hydrogen bonding interactions in our monomers, the photopolymerization behavior and implicitly the conversion degree (DC) for some experimental adhesive formulations containing acid-modified BisGMA, commercial BisGMA (only in F1-F3), triethyleneglycol dimethacrylate and 2-hydroxyethyl methacrylate were examined by FTIR spectroscopy. The water effects on the photocrosslinked networks together with the flexural strength/modulus were also investigated. The adhesive penetration into the dentin surface was surveyed by SEM analysis, and the antimicrobial activity triggered by the incorporation of 0.5wt% AgNO3, 10wt% zinc methacrylate or 1wt% triclosan methacrylate in selected adhesive formulations on the growth of Streptococcus mutans and Candida albicans strains was evidenced. RESULTS: The contribution of the hydrogen bonding interactions was found to be lower in BisGMA derivatives than in non-modified BisGMA, and the DC varied between 56.5 (F6) and 83.7% (F1) compared with a control formulation based on BisGMA:TEGDMA (DC=58.2%). The flexural strength and flexural modulus varied in the range 33.7MPa (F6) 54.4MPa (F8)MPa and 0.64 (F6)-1.43 (F8)GPa, respectively. SEM observation of adhesive-dentin interface revealed the formation of resin tags for the carboxyl containing adhesive, while for the control adhesive they are hardly formed. Also, the microorganism development was inhibited, the proposed materials displaying antimicrobial activity. SIGNIFICANCE: The experimental formulations based on carboxyl-functionalized BisGMA exhibit a similar or even improved behavior over control sample, suggesting their potential applicability as antimicrobial dental adhesives. PMID- 27671468 TI - High strength and toughness in chromatic polymer-infiltrated zirconia ceramics. AB - OBJECTIVE: To evaluate the microstructure and mechanical behavior of polymer infiltrated zirconia ceramics as a function of Fe2O3 concentration (0-0.3mol%). METHODS: Polymer-infiltrated zirconia ceramics with different concentrations of Fe2O3 were prepared by infiltration and polymerization. XRD was employed to determine phase structure. The microstructure and fracture mechanism was observed by SEM. Flexural strength and fracture toughness were measured by three-point bending method and single-edge-notched beam method, respectively. Data were analyzed by Weibull distribution. A nanoindentation system was employed to determine elastic modulus and hardness. RESULTS: With increasing content of Fe2O3, the flexural strength, fracture toughness, elastic modulus and hardness are all greatly enhanced and the chromatic behavior also improves significantly. As a tradeoff made between strength and elastic modulus, specimen containing 0.2mol% Fe2O3 is found to be the better one, with flexural strength and fracture toughness values being 336.8MPa and 3.91MPam1/2, respectively. Moreover, it maintains a relatively low elastic modulus of 88.2GPa and a moderate hardness of 4.8GPa, close to those of natural enamel. SIGNIFICANCE: This polymer-infiltrated zirconia ceramic material is a dental material of biomimetic chromatic and mechanical properties. PMID- 27671469 TI - Shrinkage behaviors of dental composite restorations-The experimental-numerical hybrid analysis. AB - OBJECTIVES: To investigate the effects of light curing protocols on the shrinkage behaviors, contraction stress, and microleakage in composite restorations by an experimental-numerical hybrid analysis. METHODS: Three groups of human molars were collected to receive different light-curing protocols: vertical or oblique curing at regular intensity, and vertical curing at reduced intensity. For each tooth, the composite fillings were consecutively placed under unbonded and bonded states, and their shrinkage behaviors were examined with a digital image correlation (DIC) technique. The strains of the unbonded restorations were input into two finite element analysis (FEA) models with settings of the composite as either homogeneous or hardened along polymerization gradients. The preliminary solutions were verified by their individual deformations in the bonded restorations. The interfacial microleakage of restorations was also determined by micro-CT scanning and compared with the FEA results. RESULTS: The bonded restorations showed centripetal shrinkage patterns with greater downward displacements than their unbonded restorations. Vertical curing at regular intensity caused the greatest shrinkage strain, contraction stress, and microleakage among the three protocols. Low-intensity curing reduced overall shrinkage strain and displacements at cervical margin, but did not prevent the formation of microleakage. Oblique curing caused asymmetric shrinkage with the tooth-shielded side revealing less deformation. Setting the polymerization dependent elastic moduli of the composite enhanced the reliability of FEA. SIGNIFICANCE: This hybrid analysis comprehensively examined the polymerization shrinkage behaviors. Both the light intensity and direction affect the shrinkages and contraction stress. Oblique curing decreases shrinkage due to the attenuated irradiation by tooth-shielding rather than modulations of shrinkage direction. PMID- 27671470 TI - Co-Cr dental alloys induces cytotoxicity and inflammatory responses via activation of Nrf2/antioxidant signaling pathways in human gingival fibroblasts and osteoblasts. AB - OBJECTIVE: Although cobalt-chromium (Co-Cr) dental alloys are routinely used in prosthodontics, the biocompatibility of Co-Cr alloys is controversial. The aims of the present study were to investigate the effects of Co-Cr alloys on human gingival fibroblasts (HGF) and osteoblasts in an in vitro model as well as their potential molecular mechanisms, focusing on NF-E2-related factor 2 (Nrf2) pathways. METHODS: Cells were directly seeded on prepared Co-Cr alloy discs (15.0mm diameter, 1.0mm thickness) or indirectly treated with Co-Cr alloy located at the bottom of an insert well and incubated for 3 days. Cytotoxicity and reactive oxygen species (ROS) production was evaluated by MTS assay and flow cytometry, respectively. Protein and mRNA levels were determined by Western blotting and RT-PCR analysis, respectively. RESULTS: Cell viability and flow cytometric assay demonstrated that the Co-Cr alloy was cytotoxic to HGFs and osteoblasts, and significantly increased ROS production. In addition, the Co-Cr alloys upregulated pro-inflamamtory cytokines (TNF-alpha, IL-1beta, IL-6, and IL 8) and increased levels of various inflammatory mediators (iNOS derived nitrite oxide, and COX-2-derived PGE2) in both cells. A mechanistic study showed that Co Cr alloys activates the NRF2 pathway and up-regulate antioxidant enzymes including heme oxygenase-1 (HO-1). Co-Cr alloys activated JAK2/STAT3, p38/ERK/JNK MAPKs and NF-kappaB signaling pathways. Furthermore, antioxidants (resveratrol and NAC) and HO-1 inhibitor (SnPP) significantly inhibited the production of ROS and inflammatory mediators, as well as the activation of NF-kappaB signaling in Co-Cr alloy stimulated HGFs and osteoblasts. SIGNIFICANCE: This study is the first to show that Co-Cr alloys exert cytotoxic and inflammatory effects via activation of Nrf2/ARE signaling and up-regulation of downstream HO-1, which could represent candidate targets for the regulation of inflammatory responses to Co-Cr alloys. PMID- 27671471 TI - Novel bioactive nanocomposite for Class-V restorations to inhibit periodontitis related pathogens. AB - OBJECTIVES: The occurrence of tooth root caries is increasing as the world population ages and tooth retention in seniors increases. Class V restorations with subgingival margins are difficult to clean and often lead to periodontitis. The objectives of this study were to develop a Class V composite containing dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and investigate mechanical properties and the inhibition of six species of periodontitis-related biofilms for the first time. METHODS: Ethoxylated bisphenol A dimethacrylate (EBPADMA) and pyromellitic glycerol dimethacrylate (PMGDM) were mixed at 1:1 mass ratio to form the resin matrix. DMAHDM, NACP, and glass particles were incorporated at 3%, 20% and 50% by mass, respectively. Six species were tested: Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Enterococcus faecalis. Colony-forming units (CFU), live/dead assay, biomass via crystal violet staining, and polysaccharide production by biofilms were determined on composites. RESULT: Adding 3% DMAHDM to composite did not affect the flexure strength and elastic modulus (p>0.1). For all six species of periodontal pathogens, the DMAHDM composite had biofilm CFU nearly three orders of magnitude less than that without DMAHDM. The killing efficacy of DMAHDM composite against the six species was: E. faecalis22 points on the ALS-Frontotemporal-Dementia-Questionnaire or >=3 points on >=2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on >=2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom onset and time from NIV initiation, respectively, to death. The impact of the explanatory variables on survival and NIV initiation were examined using Cox proportional hazards models. We included 110 ALS patients (76 men) with a mean age of 62 years. Median survival time was 4.3 years (95 % CI 3.53-5.13). Forty-seven patients (43 %) had an FS. Factors associated with shorter survival were FS, bulbar onset, older age at onset, short time to diagnosis and a C9orf72 repeat expansion. The adjusted hazard ratio (HR) for the FS was 2.29 (95 % CI 1.44-3.65, p < 0.001) in a multivariate model. Patients with an FS had a shorter survival after NIV initiation (adjusted HR 2.70, 95 % CI 1.04-4.67, p = 0.04). In conclusion, there is an association between the frontotemporal syndrome and poor survival in ALS, which remains present after initiation of NIV. PMID- 27671484 TI - Two-boundary first exit time of Gauss-Markov processes for stochastic modeling of acto-myosin dynamics. AB - We consider a stochastic differential equation in a strip, with coefficients suitably chosen to describe the acto-myosin interaction subject to time-varying forces. By simulating trajectories of the stochastic dynamics via an Euler discretization-based algorithm, we fit experimental data and determine the values of involved parameters. The steps of the myosin are represented by the exit events from the strip. Motivated by these results, we propose a specific stochastic model based on the corresponding time-inhomogeneous Gauss-Markov and diffusion process evolving between two absorbing boundaries. We specify the mean and covariance functions of the stochastic modeling process taking into account time-dependent forces including the effect of an external load. We accurately determine the probability density function (pdf) of the first exit time (FET) from the strip by solving a system of two non singular second-type Volterra integral equations via a numerical quadrature. We provide numerical estimations of the mean of FET as approximations of the dwell-time of the proteins dynamics. The percentage of backward steps is given in agreement to experimental data. Numerical and simulation results are compared and discussed. PMID- 27671485 TI - Inhibition processes are dissociable and lateralized in human prefrontal cortex. AB - The prefrontal cortex (PFC) is known to make fundamental contributions to executive functions. However, the precise nature of these contributions is incompletely understood. We focused on a specific executive function, inhibition, the ability to suppress a pre-potent response. Functional imaging and animal studies have studied inhibition. However, there are only few lesion studies, typically reporting discrepant findings. For the first time, we conducted cognitive and neuroimaging investigations on patients with focal unilateral PFC lesions across two widely used inhibitory tasks requiring a verbal response: The Hayling Part 2 and Stroop Colour-Word Tests. We systematically explored the relationship between inhibition, fluid intelligence and lesion location using voxel-based lesion symptom mapping (VLSM). We found that PFC patients were significantly impaired compared with healthy comparison group (HC) on both suppression measures of the Hayling and on the Stroop, even when performance on a fluid intelligence test was covaried. No significant relationship was found between patients' performance on each Hayling suppression measure and the Stroop, once fluid intelligence was partialled out, suggesting that the two tests may involve different kinds of inhibition. After accounting for fluid intelligence, we found a significant interaction between tests, Hayling or Stroop, and site, left or right, of PFC damage. This finding suggesting lateralized functional organization was complemented and extended by our VLSM results. We found that performance on both Hayling suppression measures significantly relied on the integrity of a similar and relatively circumscribed region within the right lateral PFC, in the right lateral superior and middle frontal gyri. In stark contrast, performance on the Stroop relies on the integrity of left lateral superior and middle frontal gyri. Thus, lesion location, right or left PFC, is critical in producing impairments on two inhibitory tasks loading similarly on verbal control. This suggests that the two suppression measures of the Hayling and the Stroop are likely to assess dissociable components of executive functions, related to anatomically defined and lateralized PFC circuits. Our findings also suggest that inhibition may actually comprise qualitatively different forms with different neural substrates. This has clinical implications for the diagnosis and treatment of disinhibition impairments, a common behavioural problem caused by PFC lesions. Our results highlight the need to assess inhibition using a variety of tasks and to develop different types of treatments. PMID- 27671486 TI - The logarithmic relaxation process and the critical temperature of liquids in nano-confined states. AB - The logarithmic relaxation process is the slowest of all relaxation processes and is exhibited by only a few molecular liquids and proteins. Bulk salol, which is a glass-forming liquid, is known to exhibit logarithmic decay of intermediate scattering function for the beta-relaxation process. In this article, we report the influence of nanoscale confinements on the logarithmic relaxation process and changes in the microscopic glass-transition temperature of salol in the carbon and silica nanopores. The generalized vibrational density-of-states of the confined salol indicates that the interaction of salol with ordered nanoporous carbon is hydrophilic in nature whereas the interaction with silica surfaces is more hydrophobic. The mode-coupling theory critical temperature derived from the QENS data shows that the dynamic transition occurs at much lower temperature in the carbon pores than in silica pores. The results of this study indicate that, under nano-confinements, liquids that display logarithmic beta-relaxation phenomenon undergo a unique glass transition process. PMID- 27671487 TI - Dendrimer nanoarchitectures for cancer diagnosis and anticancer drug delivery. AB - Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting. PMID- 27671488 TI - Assessment of health-related quality of life, mental health status and psychological distress based on the type of pharmacotherapy used among patients with depression. AB - PURPOSE: Effectiveness of antidepressants is generally comparable between and within classes. However, real-world studies on antidepressant treatment and its consequences on the overall quality of life and mental health of individuals are limited. The purpose of this study was to examine the association of specific class of antidepressants with the health-related quality of life, psychological distress and self-reported mental health of individuals suffering from depression who are on monotherapy. METHODS: This retrospective, longitudinal study included individuals with depression who were on antidepressant monotherapy, using data from 2008 to 2011 Medical Expenditure Panel Survey (MEPS). Changes in health related quality of life, self-reported mental health and psychological distress over a year's time were observed. A multinomial logistic regression model was built to examine the association between the class of antidepressant medications and the dependent variables. RESULTS: A total of 688 adults met the study inclusion criteria. No significant difference was observed in the change in Physical Component Summary (PCS), self-reported mental health and psychological distress based on the class of antidepressants. However, individuals on serotonin norepinephrine reuptake inhibitors (SNRIs) (OR 0.337, 95 % CI 0.155-0.730) were significantly less likely to show improvement on Mental Component Summary (MCS) scores as compared to those on selective serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: The study findings suggest that practitioners should be aware of the differences in the health-related quality of life of those taking SSRIs versus other classes of antidepressants. Further research needs to be done to determine the reason for SSRIs to show greater improvement on mental health as compared to SNRIs. PMID- 27671489 TI - Development of a short form of the Spanish schedule of attitudes toward hastened death in a palliative care population. AB - PURPOSE: The schedule of attitudes toward hastened death (SAHD) is widely used to assess the wish to hasten death (WTHD) among patients with life-threatening conditions. A short form of the SAHD would increase its clinical applicability in this population. METHOD: Rasch analysis of data from 101 Spanish palliative inpatients. Item reduction involved selecting items with a high discrimination index (point-biserials >=0.70), removing items with inadequate fit statistics, and assessing unidimensionality and local dependency. We examined the test probability function to establish an empirical risk score for suffering a WTHD and tested convergence between the original and the reduced set of items. RESULTS: A set of five items met all quality criteria. In this sample, 20.8 % of participants had a higher risk of a WTHD (p > 50 %) at a score of 3. Correlation analysis confirmed convergent validity between the original and reduced forms. Concurrent validity was confirmed by the similar correlations shown by both versions of the SAHD (5 and 20 items) with other measures. CONCLUSION: This 5 item Spanish form of the SAHD could be a suitable alternative to the full instrument. The cut-off score derived from the Rasch analysis may be able to detect patients at risk of a WTHD. PMID- 27671490 TI - Cardioprotector Activity of an Esteroidal Saponin: A Scientific and Technological Prospection. AB - BACKGROUND: Cardiovascular diseases are a group of disorders of the heart and blood vessels that account for a major cause of premature death worldwide. Diosgenin saponin is a steroid for therapeutic application in different clinical settings such as cardiovascular diseases, hyperglycemia and dyslipidemia control, antimicrobial, anti-viral and anti-inflammatory agent. The aim of the study was to conduct a systematic review of Diosgenin, its pharmaceutical applications and perspectives on the application in the cardiovascular system diseases. METHODS: Periodic basis ScienceDirect, PubMed and Virtual Health Library were used as well as the European Office of the technological bases Patent Office, World Intellectual Property Organization, the Office US Patent and Trademark Office and the Brazilian database National Institute of Industrial Property. The keywords used were Diosgenin, cardiovascular system, hypertension, atherosclerosis and dyslipidemia and their correlations in English and Portuguese, with publications from January 2010 to June 2015. RESULTS: After analysis of the technological and scientific bases, the results show that there is a limited number of patents showing that the Diosgenin action on the cardiovascular system is centered in the areas for chemical studies of steroid Diosgenin. In the scientific basis, the results show that there is an interesting Diosgenin action on the cardiovascular system. CONCLUSION: Therefore, studies with Diosgenin are promising on account of its significant pharmacological potential from scientific and technological viewpoints, reaching for a technology transfer to generate economic and industrial growth. PMID- 27671492 TI - Multimodality Imaging: Bird's-Eye View from the 65th Annual Scientific Sessions of the American College of Cardiology, Chicago, Ill, April 2-4, 2016. PMID- 27671491 TI - Common Substances That May Contribute to Resistant Hypertension, and Recommendations for Limiting Their Clinical Effects. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight common or important substances or habits that elevate blood pressure and offer suggestions, based on recent literature, to limit their use or effects. RECENT FINDINGS: Despite decades of advice to the general populace from public health authorities to avoid or reduce dietary sodium and non-steroidal anti-inflammatory drug (NSAID) use, more evidence has accumulated from nationwide surveys, clinical trials, and pathophysiological or mechanistic studies that show how important these modalities can (and should) be for hypertensive and prehypertensive individuals and the general population. Other common stimuli that increase blood pressure can be divided into many that are easily avoided (e.g., phenethylamines, anabolic steroids), those that must be continued for important medical reasons (e.g., erythropoietin, tyrosine kinase inhibitors) and therefore require intensified antihypertensive therapy, and a few (e.g., glucocorticoids, hormonal contraceptives) that fall between these two paradigms. PMID- 27671493 TI - Prognosis of stress-only SPECT myocardial perfusion imaging with prone imaging. AB - BACKGROUND: Stress-only single-photon emission computed tomography myocardial perfusion imaging (SO SPECT MPI) is associated with similarly benign prognosis as stress-rest SPECT MPI. However, previous studies have used attenuation correction rather than prone imaging to increase the rate of SO studies. OBJECTIVES: To assess the prognosis of SO SPECT MPI performed with prone imaging. METHODS: We performed a retrospective cohort analysis of all patients who underwent a Tc-99m gated SPECT MPI over a 58-month period. RESULTS: Two thousand four hundred and sixty five patients were followed up. Of them, 1114 (45.2%) patients had a SO supine test, 388 (15.7%) underwent a SO supine and prone test, and the remaining 963 (39.1%) patients underwent a full stress-rest SPECT MPI. There was a similar annual mortality rate between the SO supine/prone group (1.3%), the SO supine (1.5%), and the stress-rest (1.5%) group (P = 0.47). Patients in the stress-rest group were significantly more likely to suffer from myocardial infarction (MI) as compared to the other two groups with an annual rate of 0.7% as compared to 0.4% (P = 0.049). CONCLUSIONS: Normal supine-prone SO SPECT MPI is associated with a similarly benign prognosis as stress-rest SPECT MPI. The adjunction of prone imaging to the stress supine significantly increases the rate of SO SPECT MPI. PMID- 27671495 TI - Treatment of massive subretinal hemorrhage from polypoidal choroidal vasculopathy and age-related macular degeneration. PMID- 27671494 TI - Comparison of Scheimpflug and swept-source anterior segment optical coherence tomography in normal and keratoconus eyes. AB - PURPOSE: The purpose of the study was to assess the agreement of anterior segment optical coherence tomography with its older well-known opponent i.e., Sheimpflug imaging in evaluation of the cornea in normal and keratoconus subjects. METHODS: 107 normal and 56 keratoconus eyes were evaluated with the anterior segment optical coherence tomography followed by the Scheimpflug imaging. Parameters included axial keratometry data in both of steep and flat meridians, mean keratometry and the astigmatism values in the central 4.0 mm zone, central, thinnest and apex corneal thicknesses, Q-value in 8 mm zone and pupil diameter. Corneal topographic maps were recorded and were evaluated for anterior highest and lowest points, posterior highest and lowest points. Average values were recorded for analysis. RESULTS: All anterior cornea keratometry indices showed perfect agreement between two devices in normal corneas; while the level of agreement in keratoconus cases ranged from moderate to strong. All posterior keratometry indices also showed perfect agreement in both groups; except for flat K in normal corneas and steep K in KC ones. The amount of corneal cylinder in normal corneas had perfect agreement, and moderate to strong agreement in anterior/posterior cornea in keratoconus group. Anterior highest and lowest points showed strong and perfect agreement in normal and keratoconus cases, respectively. Posterior highest and lowest points showed strong agreement in normal cases. Thickness indices (central, thinnest, and apex thicknesses) showed perfect agreement between two devices in both normal and KC groups. Mean values of anterior and posterior highest points were statistically higher in Scheimpflug system. CONCLUSIONS: Although two imaging technologies had statistically numerical different output, it seems that they have a good agreement in most parameters. PMID- 27671496 TI - Tetrahydroindazole derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists. AB - A series of potent and receptor-selective cannabinoid-1 (CB1) receptor inverse agonists has been discovered. Peripheral selectivity of the compounds was assessed by a mouse tissue distribution study, in which the concentrations of a test compound in both plasma and brain were measured. A number of peripherally selective compounds have been identified through this process. Compound 2p was further evaluated in a 3-week efficacy study in the diet-induced obesity (DIO) mouse model. Beneficial effects on plasma glucose were observed from the compound treated mice. PMID- 27671498 TI - Identification and optimization of a new series of anti-tubercular quinazolinones. AB - A high throughput phenotypic screening against Mycobacterium smegmatis led us to the discovery of a new class of bacteriostatic, highly hydrophobic antitubercular quinazolinones that potently inhibited the in vitro growth of either extracellular or intramacrophagic M. tuberculosis (Mtb), via modulation of an unidentified but yet novel target. Optimization of the initial hit compound culminated in the identification of potent but poorly soluble Mtb growth inhibitors, three of which were progressed to in vivo efficacy studies. Despite nanomolar in vitro potency and attractive PK properties, none of these compounds was convincingly potent in our in vivo mouse tuberculosis models. This lack of efficacy may be linked to the poor drug-likeness of the test molecules and/or to the properties of the target. PMID- 27671497 TI - Synthesis of 3,5-dihydroxy-7,8-dimethoxy-2-(4-methoxyphenyl)benzopyran-4-one derivatives as anticancer agents. AB - Different alkyl amide (15a-l) and alkyl amine (16a-e) derivatives of 7,8 dimethoxy-3-hydroxy-2-(4-methoxyphenyl)benzopyran-4-one were synthesized and evaluated for their anticancer activity against five different cancer cell lines using SRB assay. Compounds 15e, 15i, 15j and 16a-e showed significant anticancer activity within the range of IC50 2.58-34.86MUM. The most promising molecule, 16c, was further analyzed for its effect on cell cycle and apoptosis of estrogen receptor positive cancer cells (MCF-7 cells) which showed that 16c triggered apoptosis in MCF-7 cells and arrested cells population at sub-G0 (apoptotic) and G2M phase. In tubulin polymerization assay, 16c interfered with kinetics of tubulin polymerization. PMID- 27671499 TI - Tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists. AB - Peripherally restricted CB1 receptor inverse agonists hold potential as useful therapeutics to treat obesity and related metabolic diseases without causing undesired CNS-mediated adverse effects. We identified a series of tetrahydropyrazolo[4,3-c]pyridine derivatives as potent and highly peripherally selective CB1 receptor inverse agonists. This discovery was achieved by introducing polar functional groups into the molecule, which increase the topological polar surface area and reduce its brain-penetrating ability. PMID- 27671500 TI - Wortmannilactones I-L, new NADH-fumarate reductase inhibitors, induced by adding suberoylanilide hydroxamic acid to the culture medium of Talaromyces wortmannii. AB - With the aim of finding more potential inhibitors against NADH-fumarate reductase (specific target for treating helminthiasis and cancer) from natural resources, Talaromyces wortmannii was treated with the epigenome regulatory agent suberoylanilide hydroxamic acid, which resulted in the isolation of four new wortmannilactones derivatives (wortmannilactones I-L, 1-4). The structures of these new compounds were elucidated based on IR, HRESIMS and NMR spectroscopic data analyses. These four new compounds showed potent inhibitory activity against NADH-fumarate reductase with the IC50 values ranging from 0.84 to 1.35MUM. PMID- 27671501 TI - HMG-CoA synthase isoenzymes 1 and 2 localize to satellite glial cells in dorsal root ganglia and are differentially regulated by peripheral nerve injury. AB - In dorsal root ganglia (DRG), satellite glial cells (SGCs) tightly ensheathe the somata of primary sensory neurons to form functional sensory units. SGCs are identified by their flattened and irregular morphology and expression of a variety of specific marker proteins. In this report, we present evidence that the 3-hydroxy-3-methylglutaryl coenzyme A synthase isoenzymes 1 and 2 (HMGCS1 and HMGCS2) are abundantly expressed in SGCs. Immunolabeling with the validated antibodies revealed that both HMGCS1 and HMGCS2 are highly colabeled with a selection of SGC markers, including GS, GFAP, Kir4.1, GLAST1, GDNF, and S100 but not with microglial cell marker Iba1, myelin sheath marker MBP, and neuronal marker beta3-tubulin or phosphorylated CaMKII. HMGCS1 but not HMGCS2 immunoreactivity in SGCs is reduced in the fifth lumbar (L5) DRGs that contain axotomized neurons following L5 spinal nerve ligation (SNL) in rats. Western blot showed that HMGCS1 protein level in axotomized L5 DRGs is reduced after SNL to 66+/-8% at 3 days (p<0.01, n=4 animals in each group) and 58+/-13% at 28 days (p<0.001, n=9 animals in each group) of its level in control samples, whereas HMGCS2 protein was comparable between injured and control DRGs. These results identify HMGCSs as the alternative markers for SGCs in DRGs. Downregulated HMGCS1 expression in DRGs after spinal nerve injury may reflect a potential role of abnormal sterol metabolism of SGCs in the nerve injured-induced neuropathic pain. PMID- 27671503 TI - The role of personality in dyadic interaction: A psychophysiological study. AB - Psychophysiological activity was recorded during development discussions of 44 manager-subordinate pairs to examine the effects of the Big Five personality traits Extraversion and Conscientiousness, and personality similarity during dyadic social interaction. Facial electromyography and frontal electroencephalography (EEG) asymmetry were collected continuously during the 30 min discussions. Different actor and partner effects and Actor*Partner interactions were observed. Matching levels of Extraversion led to higher periocular muscle activity, indicating positive valence emotional expressions. The results are discussed considering similarity attraction theories. PMID- 27671502 TI - Genome-wide association study of working memory brain activation. AB - In a population-based genome-wide association (GWA) study of n-back working memory task-related brain activation, we extracted the average percent BOLD signal change (2-back minus 0-back) from 46 regions-of-interest (ROIs) in functional MRI scans from 863 healthy twins and siblings. ROIs were obtained by creating spheres around group random effects analysis local maxima, and by thresholding a voxel-based heritability map of working memory brain activation at 50%. Quality control for test-retest reliability and heritability of ROI measures yielded 20 reliable (r>0.7) and heritable (h2>20%) ROIs. For GWA analysis, the cohort was divided into a discovery (n=679) and replication (n=97) sample. No variants survived the stringent multiple-testing-corrected genome-wide significance threshold (p<4.5*10-9), or were replicated (p<0.0016), but several genes were identified that are worthy of further investigation. A search of 529,379 genomic markers resulted in discovery of 31 independent single nucleotide polymorphisms (SNPs) associated with BOLD signal change at a discovery level of p<1*10-5. Two SNPs (rs7917410 and rs7672408) were associated at a significance level of p<1*10-7. Only one, most strongly affecting BOLD signal change in the left supramarginal gyrus (R2=5.5%), had multiple SNPs associated at p<1*10-5 in linkage disequilibrium with it, all located in and around the BANK1 gene. BANK1 encodes a B-cell-specific scaffold protein and has been shown to negatively regulate CD40-mediated AKT activation. AKT is part of the dopamine-signaling pathway, suggesting a mechanism for the involvement of BANK1 in the BOLD response to working memory. Variants identified here may be relevant to (the susceptibility to) common disorders affecting brain function. PMID- 27671504 TI - Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders. AB - Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N=454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically oriented research on psychopathology. PMID- 27671505 TI - Right frontal gamma and beta band enhancement while solving a spatial puzzle with insight. AB - Solving a problem with an "a-ha" effect is known as insight. Unlike incremental problem solving, insight is sudden and unique, and the question about its distinct brain activity, intrigues many researchers. In this study, electroencephalogram signals were recorded from 12 right handed, human participants before (baseline) and while they solved a spatial puzzle known as the '10 coin puzzle' that could be solved incrementally or by insight. Participants responded as soon as they reached a solution and reported whether the process was incremental or by sudden insight. EEG activity was recorded from 19 scalp locations. We found significant differences between insight and incremental solvers in the Gamma and Beta 2 bands in frontal areas (F8) and in the alpha band in right temporal areas (T6). The right-frontal gamma indicates a process of restructuring which leads to an insight solution, in spatial problems, further suggesting a universal role of gamma in restructuring. These results further suggest that solving a spatial puzzle via insight requires exclusive brain areas and neurological-cognitive processes which may be important for meta cognitive components of insight solutions, including attention and monitoring of the solution. PMID- 27671506 TI - Optimizing neuronal differentiation of human pluripotent NT2 stem cells in monolayer cultures. AB - Human pluripotent embryonal carcinoma (NT2) cells are increasingly considered as a suitable model for in vitro developmental toxicity and neurotoxicity (DT/DNT) studies as they undergo neuronal differentiation upon stimulation with retinoic acid (RA) and allow toxicity testing at different stages of maturation. However, differentiation of NT2 cells is not straightforward. There are different protocols available in the literature reporting varying results with regard to differentiation efficiency, expression of neuronal markers and morphological characteristics of differentiated cells. Yet, the efficiency of available protocols has not been systematically compared. To address this question, we quantified the number and size of cell cluster formed during differentiation using published and modified protocols and analyzed the abundance of neuronal and non-neuronal expression markers using immunocytochemistry. In the course of the experiments we observed that differentiation results strongly depend on the cell density at differentiation-initiation as well as on the type of used cell culture plastic ware. Based on those observations and the results from our comparative analysis, we created our own optimized and robust protocol that reproducibly reveals differentiated cells with high yield. We conclude that our method may be superior to differentiation of NT2 cells for systematic in vitro-based primary screening for developmental toxicants and neurotoxicants at different stages of maturation over previous protocols used. Our approach will also contribute to reduce animal testing in the context of the 3Rs. PMID- 27671507 TI - Whole Tumor Cell Vaccine Adjuvants: Comparing IL-12 to IL-2 and IL-15. AB - Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently under intensive investigation in preclinical and clinical trials. Cancer vaccines induce permanent activation of the immune system and may be considered the most promising method for cancer treatment, especially in combination with other agents of passive immunotherapy. Among various approaches to cancer vaccines, whole tumor cell vaccines have been attracting attention for several years. Despite their low to moderate clinical effects, these vaccines have numerous advantages. Their ability to generate immune responses against tumor-associated antigens reduces the possibility for tumor cells to escape and facilitates the development of "off-the-shelf" allogeneic tumor vaccines. Understanding the reciprocal interactions between tumor cells and leukocytes is a key to harness the full potential of whole cell vaccination. Cytokines are considered as potent immunomodulatory molecules which behave as adjuvants in whole tumor cell vaccines. Improved mechanistic understanding of key cytokines in tumor immunity will serve as a resource for rational design of whole cell cancer vaccines. Although there are several reports about the use of different immunostimulatory cytokines as adjuvants, interleukin (IL)-12 appears to have superior effects compared to other cytokines. This review describes the effects of IL-12 compared to other immunomodulatory cytokines, such as IL-2 and IL-15, and highlights its application in whole cell tumor vaccination. PMID- 27671508 TI - Regulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer. AB - BACKGROUND: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer. OBJECTIVE: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer. METHODS: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease (PUD, n=25), and gastric cancer (GC, n=27) according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD4+CD25+FoxP3+Tregs and CD14+HLA-DR- MDSCs were determined in all patients, by flow cytometry. The number of FoxP3+ regulatory T cells was also determined by immunohistochemistry (IHC). RESULTS: The percentage of peripheral blood Treg cells in both PUD (0.81 +/- 0.39, p<0.001) and GC groups (0.98 +/- 0.65, p<0.001) were significantly higher than in NUD group (0.46 +/- 0.10). These results were also confirmed by IHC. A significantly higher percentage of MDSCs in patients with PUD (0.73 +/- 0.19, p<0.001) and GC (0.73 +/- 0.16, p<0.001) was also observed when compared to NUD group (0.46 +/- 0.16). There was no difference in the percentages of these two cell types between the PUD and GC groups. The percentages of Tregs and MDSCs in patients with PUD and GC were not significantly correlated. CONCLUSIONS: Both Tregs and MDSCs showed higher frequencies in PUD and GC. These results suggest that immune-modulation by the Tregs and MDSCs may play a role in the pathogenesis of PUD and GC. PMID- 27671509 TI - Natural Killer Cell Cytotoxicity Against SKOV3 after HLA-G Downregulation by shRNA. AB - BACKGROUND: HLA-G is a nonclassical HLA class I molecule which, when elevated in tumor cells, is one of the main factors involved in tumor evasion of immune responses including NK and T cells. OBJECTIVE: To evaluate the effect of HLA-G downregulation on NK cell cytotoxicity in tumor cell lines. METHODS: The expression level of HLA-G was measured by real-time PCR and flowcytometry after transfection of SKOV3 by shRNA.1, which targets specific sequences in exon 4, or shRNA.2, which targets both exons 4 and 6. NK-92MI cell cytotoxicity against transfected or untransfected target cell lines was measured with the lactate dehydrogenase (LDH) release assay. The Jeg-3 cell line was used as a positive control. RESULTS: Membrane-bound HLA-G expression levels decreased significantly in both cell lines after transfection with both shRNAs compared to their corresponding untransfected cells (p<0.05). Jeg-3 cells were better lysed than SKOV3 cells by NK cells during the first 48 h after transfection with both shRNAs. Compared to untransfected cells, shRNA.1-transfected SKOV3 cells were significantly more lysed by NK cells 24 h post-transfection (p=0.043). CONCLUSION: As a clinical approach, HLA-G downregulation with shRNA may be effective in cancer therapy by improving immune cell activation. PMID- 27671510 TI - Altered Serum Cytokine Profiles in Relapse Phase of Relapsing-Remitting Multiple Sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. OBJECTIVE: To determine levels of different cytokines in patients with relapsing remitting MS (RR-MS) compared to healthy controls. METHODS: Profiles of pro inflammatory, Th1-, Th2-, and Th17-related cytokines were compared by quantitative multiplexed ELISA-based chemiluminescent assay in 44 RR-MS and 44 healthy age- and sex-matched individuals from the same ethnicity. RESULTS: Among pro-inflammatory cytokines, the levels of IL-6 (p=0.003), IL-8 (p=0.05) and TNF alpha (p=0.002) were higher in patients than controls, though IL-4 and IL-10 as well as SigmaTh2 cytokines were lower in patients (p=0.05, p=0.02 and p=0.05, respectively). After gender classification, the higher levels of IL-4 in male patients remained significant and IL-13 also showed significantly higher levels in male patients compared to male controls (p=0.003 and p=0.05, respectively). A significant negative correlation was detected between EDSS and IL-10 or SigmaTh2 levels (p=0.005). In addition, IL-1alpha (r=0.4, p=0.05) and IFN-gamma (r=0.35, p=0.05) were also directly correlated with EDSS in female patients. CONCLUSIONS: Patients with RR MS who are in the relapse clinical phase exhibit higher levels of pro-inflammatory cytokines and reduction in protective Th2-related cytokines. PMID- 27671511 TI - Effect of TNF-alpha Blockade in Gingival Crevicular Fluid on Periodontal Condition of Patients with Rheumatoid Arthritis. AB - BACKGROUND: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-alpha)-induced bone resorption that is involved in the pathogenesis of both. OBJECTIVES: To investigate the effect of TNF-alpha blockade on periodontal conditions in patients with active RA. METHOD: The periodontal statuses of 36 patients (26 females, 10 males) diagnosed with active RA were evaluated both before and after anti-TNF-alpha therapy. Gingival index, bleeding on probing (BOP), probing pocket depth (PPD), oral hygiene index (OHI), and levels of TNF-alpha in gingival crevicular fluid (GCF) were measured at the baseline and 6 weeks after the treatment. Wilcoxon signed ranked test was used for statistical analyses. RESULTS: Based on OHI (p=0.860), the level of plaque control did not change during the study period, but there was a significant reduction in gingival inflammation based on the mean BOP (p=0.049) and GI (p=0.036) before and after 6 weeks of anti-TNF-alpha therapy. The mean PPD index did not significantly differ at the baseline and 6 weeks after treatment (p=0.126). CONCLUSION: Anti-TNF-alpha therapy might have a desirable effect on periodontal conditions and might reduce TNF-alpha level in GCF of patients with RA. PMID- 27671512 TI - Immunogenicity of 23-Valent Pneumococcal Vaccine in Children with Systemic Lupus Erythematosus. AB - BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is characterized by B-cell abnormality and auto-antibody generation. Since bacterial infections are the most important causes of mortality in these patients, pneumococcal vaccination is recommended for children with SLE. OBJECTIVE: To investigate humoral immunity and specific-antibody formation in response to a 23-valent polysaccharide pneumococcal vaccination in SLE children and asthmatic control group. METHOD: The case and control groups consisted of 30 children with the mean age of 13 years who were matched by sex and age. Anti pneumococcal antibody titers were determined using Enzyme-Linked Immunosorbent Assay (ELISA) before the vaccination with the 23-valent pneumococcal vaccine and 3 weeks later in both groups. Also the correlation between anti-pneumococcal antibody titer and different factors including age, sex, lupus activity, disease duration, medications, history of recurrent infections, and laboratory data were investigated. RESULTS: Both groups showed significant increases in anti pneumococcal antibody level after vaccination (p<=0.001). The increase in antibody level were almost the same in both groups (p>=0.05) such that 77.7% of SLE children and 86.2% of control children showed at least 2-fold increase in anti-pneumococcal antibody titer following immunization. Significant correlations were seen between the level of post-immunization anti-pneumococcal antibody with the age of children with SLE (p=0.02) and their age of disease onset (p=0.02). CONCLUSION: It is concluded that pneumococcal vaccination is generally immunogenic in children with SLE. However, a small group of patients show impaired response to the vaccine. PMID- 27671513 TI - The Immunostimulatory Effect of Lactic Acid Bacteria in a Rat Model. AB - BACKGROUND: Probiotics are "live", beneficial microbes that provide important health benefits in their hosts. There is significant interest in the modulation and regulation of the immune function by probiotics. OBJECTIVE: To investigate the immunomodulatory effects of a probiotic mixture, including Lactobacillus and Bifidobacterium species, by detecting serum cytokine and immunoglobulin levels. METHODS: The rats were randomly divided into 4 groups. The first group was "Control group" and other 3 groups were probiotic application groups who received different doses of probiotics. The probiotic mixture included 12 probiotic bacteria, mostly Lactobacillus and Bifidobacterium strains. Probiotic mixture was administered to rats for 12 consecutive days. TNF-alpha, TGF-beta, IL-1-beta, IL 6, and IL-10 levels as well as serum IgG and IgA concentrations were detected in the sera after 12 days. RESULTS: Probiotics led to a decrease in the levels of TNF-alpha, IL-6 and TGF-beta; however, they led to increase in the serum levels of IL-10, IgG and IgA. There were significant differences between control group and probiotic application groups (p<0.05). CONCLUSION: These data suggest that the commensal microbiota are important for stimulating both proinflammatory and regulatory responses in order to rapidly clear infections and minimize inflammation-associated tissue damage. PMID- 27671514 TI - Maternal Serum and Cervicovaginal IL-6 in Patients with Symptoms of Preterm Labor. AB - BACKGROUND: Preterm birth is a common problem in obstetrics. OBJECTIVE: To measure maternal serum interlukin-6 in mothers with preterm uterine contractions and compare it with cervicovaginal interlukin-6 in the same women. METHODS: In this cross-sectional study, we measured interlukin-6 in the sera and cervicovaginal fluids of 86 women with preterm uterine contractions. All participants had an intact membrane. Interlukin-6 was measured by using ELISA method. Statistical analysis was done using U-Mann Whitney, Chi-Square and Kendall's tests. RESULTS: The mean and median (Quartile25, Quartile75) of interlukin-6 in cervicovaginal fluid was higher than maternal serum interlukin-6. There was a statically significant difference in the median of interlukin-6 in sera and cervicovaginal fluid (P<0.0001). There was no significant correlation between serum and cervicovaginal interlukin-6 (r=0.048, p=0.548). CONCLUSION: We found no relationship between serum interlukin-6 and preterm labor and the maternal serum Interlukin-6 does not seem to be a suitable biomarker for predicting preterm delivery. PMID- 27671515 TI - Processes of plasma protein N-homocysteinylation in multiple sclerosis. AB - BACKGROUND: Homocysteine thiolactone (HTL) is a cyclic thioester of homocysteine (Hcy) contributing to the toxicity of this amino acid. HTL spontaneously reacts with protein lysine residues leading to altered properties of target proteins and induction of immune response. HTL is hydrolyzed to Hcy by plasma enzyme, paraoxonase 1 (PON1). Although both Hcy and PON1 may be involved in the pathogenesis of multiple sclerosis (MS), protein modification by HTL in this disease has not been studied so far. Purpose/Aim: The aim of this study was to assess the level of Hcy, HTL and autoantibodies against N-homocysteinylated proteins as well as PON1 activity in patients with MS. METHODS: The studies were performed in 61 MS patients with relapsing-remitting (RR group, n = 25) and secondary-progressive type of MS (SP group, n = 36), and in healthy people (C - control group, n = 44). RESULTS: Homocysteine level was significantly higher in MS patients comparing to control group (C vs. RR p < 0.01; C vs. SP p < 0.05). The level of HTL tended to be higher in RR-MS in comparison to control group, but it did not reach the level of significance. The level of antibodies against N homocysteinylated proteins did not differ significantly between studied groups. PON1 activity was significantly lower in SP type of MS (SP vs. C p < 0.05; SP vs. RR p < 0.05). CONCLUSIONS: Although plasma Hcy concentration is higher in MS patients and PON1 activity is reduced in the SP form, MS is associated with minor or no changes in protein-attached HTL and anti-homocysteinylated protein immune response. PMID- 27671517 TI - 5-Aminolevulinic acid in intraoperative photodynamic therapy of bladder cancer (results of multicenter trial). AB - The results of multicenter prospective trial for efficacy of combined modality treatment: transurethral resection (TUR)+photodynamic therapy (PDT) with alasens for bladder cancer are represented in the article. Trials were organized by Research Institute of Organic Intermediates and Dyes and conducted according to clinical protocol approved by Ministry of Health of Russia, at the sites of leading Russian cancer clinical centers. The trial included 45 subjects with verified diagnosis of non-muscle-invasive bladder cancer. Patients underwent TUR of bladder with simultaneous PDT as anti-relapse treatment. Alasens was administered to patients as intravesicular instillation of 3% solution in volume of 50ml with 1.5-2h exposure (prior to TUR). TUR was performed after instillation. PDT session was conducted immediately after the completion of TUR on a single occasion by means of combined local irradiation on tumor bed with diffuse irradiation on whole urinary bladder mucosa (light dose of local irradiation - 100J/cm2, diffuse irradiation - 20J/cm2). Good tolerance of the treatment was noticed, there were no complications. Among 45 patients included in the trial, 35 (78%) completed 12 month protocol follow-up without relapse. In our study PDT with alasens after TUR reported a recurrence rate of non-muscle invasive bladder cancer for 1st year after treatment of 22%. TUR with intraoperative PDT with 5-aminolevulinic acid may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer. PMID- 27671516 TI - Triblock copolymers encapsulated poly (aryl benzyl ether) dendrimer zinc(II) phthalocyanine nanoparticles for enhancement in vitro photodynamic efficacy. AB - A novel series of nanoparticles formed via an electrostatic interaction between the periphery of negatively charged 1-2 generation aryl benzyl ether dendrimer zinc (II) phthalocyanines and positively charged poly(L-lysin) segment of triblock copolymer, poly(L-lysin)-block-poly(ethylene glycol)-block-poly(L lysin), was developed for the use as an effective photosensitizers in photodynamic therapy. The dynamic light scattering, atomic force microscopy showed that two nanoparticles has a relevant size of 80-150nm. The photophysical properties and singlet oxygen quantum yields of free dendrimer phthalocyanines and nanoparticles exhibited generation dependence. The intracellular uptake of dendrimer phthalocyanines in Hela cells was significantly elevated as they were incorporated into the micelles, but was inversely correlated with the generation of dendrimer phthalocyanines. The photocytotoxicity of dendrimer phthalocyanines incorporated into polymeric micelles was also increased. The presence of nanoparticles induced efficient cell death. Using a mitochondrial-sepcific dye rhodamine 123 (Rh123), our fluorescence microscopic result indicated that nanoparticles localized to the mitochondria. PMID- 27671518 TI - Biochemical assessment of human uterine cervix by micro-Raman mapping. AB - Raman spectroscopy and mapping are capable of probing the molecular changes due to oncogenesis. Here Raman maps of cervical tissues under different pathological conditions were studied. Multivariate analytical methods were utilized to reconstruct these Raman maps and were compared with Hematoxylin and Eosin stained histological images. The maps showed clear differences between the different regions of the tissue and there were spectral changes associated with neoplasia and malignancy. A semi-quantitative biochemical modeling was carried out to quantify these spectral changes and the relative contributions of the biochemicals. This method revealed gradual biochemical changes (nucleus to cytoplasm ratio, glycogen, collagen, lipids, protein and carotene) associated with the progression of cervical cancer. These biomolecules extracted for the disease prognosis would have greater significance for cervical cancer diagnosis. PMID- 27671519 TI - Optimization of ultrasonic circulating extraction of samara oil from Acer saccharum using combination of Plackett-Burman design and Box-Behnken design. AB - In this study, ultrasonic circulating extraction (UCE) technique was firstly and successfully applied for extraction of samara oil from Acer saccharum. The extraction kinetics were fitted and described, and the extraction mechanism was discussed. Through comparison, n-hexane was selected as the extraction solvent, the influence of solvent type on the responses was detailedly interpreted based on the influence of their properties on the occurrence and intensity of cavitation. Seven parameters potentially influencing the extraction yield of samara oil and content of nervonic acid, including ultrasound irradiation time, ultrasound irradiation power, ultrasound temperature, liquid-solid ratio, soaking time, particle size and stirring rate, were screened through Plackett-Burman design to determine the significant variables. Then, three parameters performed statistically significant, including liquid-solid ratio, ultrasound irradiation time and ultrasound irradiation power, were further optimized using Box-Behnken design to predict optimum extraction conditions. Satisfactory yield of samara oil (11.72+/-0.38%) and content of nervonic acid (5.28+/-0.18%) were achieved using the optimal conditions. 1% proportion of ethanol in extraction solvent, 120 degrees C of drying temperature and 6.4% moisture were selected and applied for effective extraction. There were no distinct differences in the physicochemical properties of samara oil obtained by UCE and Soxhlet extraction, and the samara oil obtained by UCE exhibited better antioxidant activities. Therefore, UCE method has enormous potential for efficient extraction of edible oil with high quality from plant materials. PMID- 27671520 TI - The effect of foot overpronation on Achilles tendon blood supply in healthy male subjects. AB - The purpose of this study was to investigate Achilles tendon blood flow in individuals with overpronated feet during non-weight- and weight-bearing positions. Achilles tendon blood flow was measured by means of the pulsatility index (PI) and the resistance index (RI) in 15 male individuals with overpronated feet and 15 counterparts with normal feet, using power Doppler ultrasonography (PDI). Achilles tendon ultrasonographic (US) assessment was performed at its musculo-tendinous junction (MTJ), mid-tendon (MT), and osseotendinous junction (OTJ) at a non-weight-bearing relaxed position (RP) and during two-leg stance (TLS) and one-leg upright stance (OLS). PI and RI indices were significantly greater in individuals with overpronated feet compared to individuals with normal feet at the OTJ in OLS position (P < 0.01), and at MT in both TLS (P < 0.001) and OLS positions (P < 0.001). All individuals demonstrated also greater PI and RI indices at MT followed by the OTJ and MTJ in all positions (P < 0.001), and in OLS compared to TLS and the RP at the OTJ (P < 0.01) as well as at MT and MTJ (P < 0.001). The findings of the present study suggest that foot overpronation may affect Achilles tendon blood flow, particularly at mid-tendon, thus enhancing the possibility for injury. PMID- 27671521 TI - Editorial. PMID- 27671522 TI - Primary familial brain calcification in the 'IBGC2' kindred: All linkage roads lead to SLC20A2. AB - BACKGROUND: Linkage analyses of families with primary familial brain calcification (formerly idiopathic basal ganglia calcification [IBGC]) identified 3 candidate loci (IBGC1-3). Recently, SLC20A2 mutations were found in the IBGC1 and IBGC3 families, merging these 2 loci. We here elucidate the genetic cause of primary familial brain calcification in the 'IBGC2' kindred. METHODS: We sequenced known primary familial brain calcification genes and quantified SLC20A2 and PDGFB. Moreover, CT scans of affected and unaffected family members were evaluated by 2 blinded neuroradiologists for distribution of brain calcification. RESULTS: A heterozygous multiexonic SLC20A2 deletion was detected in several affected family members. A reevaluation of neuroimaging data revealed a subset of mutation-negative individuals with only mild and/or unilateral calcification. CONCLUSIONS: The identified SLC20A2 mutation resolves the genetic cause of primary familial brain calcification in the 'IBGC2' kindred, collapsing 'IBGC2' into IBGC1. We suggest an algorithm for predicting the chances of finding genetic mutations that has to be validated in further studies. Our study enhances criteria for the evaluation of neuroimaging data, contributing further to the much needed harmonization of diagnostic and research data collection in primary familial brain calcification. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27671524 TI - Helium and methane sources and fluxes of shallow submarine hydrothermal plumes near the Tokara Islands, Southern Japan. AB - Shallow submarine volcanoes have been newly discovered near the Tokara Islands, which are situated at the volcanic front of the northern Ryukyu Arc in southern Japan. Here, we report for the first time the volatile geochemistry of shallow hydrothermal plumes, which were sampled using a CTD-RMS system after analyzing water column images collected by multi-beam echo sounder surveys. These surveys were performed during the research cruise KS-14-10 of the R/V Shinsei Maru in a region stretching from the Wakamiko Crater to the Tokara Islands. The 3He flux and methane flux in the investigated area are estimated to be (0.99-2.6) * 104 atoms/cm2/sec and 6-60 t/yr, respectively. The methane in the region of the Tokara Islands is a mix between abiotic methane similar to that found in the East Pacific Rise and thermogenic one. Methane at the Wakamiko Crater is of abiotic origin but affected by isotopic fractionation through rapid microbial oxidation. The helium isotopes suggest the presence of subduction-type mantle helium at the Wakamiko Crater, while a larger crustal component is found close to the Tokara Islands. This suggests that the Tokara Islands submarine volcanoes are a key feature of the transition zone between the volcanic front and the spreading back arc basin. PMID- 27671523 TI - Women's and clinicians perspectives of presentation with reduced fetal movements: a qualitative study. AB - BACKGROUND: Worldwide maternal perception of fetal movements has been used for many years to evaluate fetal wellbeing. It is intuitively regarded as an expression of fetal well-being as pregnancies in which women consistently report regular fetal movements have very low morbidity and mortality. Conversely, maternal perception of reduced fetal movements is associated with adverse pregnancy outcomes. We sought to gain insight into pregnant women's and clinicians views and experiences of reduced movements. METHOD: We performed qualitative semi-structured interviews with pregnant women who experienced reduced fetal movements in their current pregnancy and health professionals who provide maternity care. Our aim was to develop a better understanding of events, facilitators and barriers to presentation with reduced fetal movements. Data analysis was conducted using framework analysis principles. RESULTS: Twenty-one women and 10 clinicians were interviewed. The themes that emerged following the final coding were influences of social network, facilitators and barriers to presentation and the desire for normality. CONCLUSIONS: This study aids understanding about why women present with reduced movements and how they reach the decision to attend hospital. This should inform professionals' views and practice, such that appreciating and addressing women's concerns may reduce anxiety and make presentation with further reduced movements more likely, which is desirable as this group is at increased risk of adverse outcome. To address problems with information about normal and abnormal fetal movements, high-quality information is needed that is accessible to women and their families. PMID- 27671525 TI - Physiological and molecular responses to bariatric surgery: markers or mechanisms underlying T2DM resolution? AB - Bariatric surgery is currently the most effective treatment for obesity and associated comorbidities, including rapid resolution of type 2 diabetes mellitus (T2DM). Although the weight loss itself has substantial impact, bariatric surgery also has weight loss-independent effects on T2DM. Several variations of bariatric surgery exist, including the widely studied Roux-en-Y gastric bypass and vertical sleeve gastrectomy. The success of both of these bariatric surgeries was originally attributed to restrictive and malabsorptive modes of action; however, mounting evidence from both human and animal studies implicates mechanisms beyond surgery-induced mechanical changes to the gastrointestinal (GI) system. In fact, with bariatric surgery comes a spectrum of physiological responses, including postprandial enhancement of gut peptide and bile acids levels, restructuring of microbial composition, and changes in GI function and morphology. Although many of these processes are also essential for glucoregulation, the independent role of each in the success of surgery is still an open question. In this review, we explore whether these changes are necessary for the improvements in body mass and glucose homeostasis or whether they are simply markers of the physiological effect of surgery. PMID- 27671526 TI - Regulation, sensory domains and roles of two Desulfovibrio desulfuricans ATCC27774 Crp family transcription factors, HcpR1 and HcpR2, in response to nitrosative stress. AB - In silico analyses identified a Crp/Fnr family transcription factor (HcpR) in sulfate-reducing bacteria that controls expression of the hcp gene, which encodes the hybrid cluster protein and contributes to nitrosative stress responses. There is only one hcpR gene in the model sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, but two copies in Desulfovibrio desulfuricans 27774, which can use nitrate as an alternative electron acceptor to sulfate. Structures of the D. desulfuricans hcpR1, hcpR2 and hcp operons are reported. We present evidence that hcp expression is regulated by HcpR2, not by HcpR1, and that these two regulators differ in both their DNA-binding site specificity and their sensory domains. HcpR1 is predicted to be a b-type cytochrome. HcpR1 binds upstream of the hcpR1 operon and its synthesis is regulated coordinately with hcp in response to NO. In contrast, hcpR2 expression was not induced by nitrate, nitrite or NO. HcpR2 is an iron-sulfur protein that reacts with NO and O2 . We propose that HcpR1 and HcpR2 use different sensory mechanisms to regulate subsets of genes required for defense against NO-induced nitrosative stress, and that diversification of signal perception and DNA recognition by these two proteins is a product of D. desulfuricans adaptation to its particular environmental niche. PMID- 27671529 TI - The effect of contouring on fatigue resistance of three types of fracture fixation plates. AB - BACKGROUND: Metallic reconstruction plates used for fracture stabilization typically require intraoperative contouring for patient-specific anatomical fit. Despite this, characterization of plate mechanical properties after contouring has previously been limited. The objective of this study was to assess whether contouring affects fatigue resistance for three types of Stryker seven-hole stainless steel (SS) 316LVM fracture fixation plates. The hypothesis was that for each plate type, more contouring repetitions would result in lower fatigue resistance. METHODS: Plates were contoured using a bench-top plate bender to +/ 20 degrees either 0*, 3*, 6*, or 9* (n = 5 per group) and tested in the straight configuration. Cyclic four-point bending was applied in an incremental stepwise staircase approach (one step = 100,000 cycles, 10 Hz) until failure (defined as brittle fracture or plastic deformation of 10 degrees permanent bend). Moment cycle product (MCP) was computed as the summation of maximum moment * number of cycles and used as the primary measure of fatigue resistance. RESULTS: No significant differences in fatigue resistance were detected between contouring groups for Basic Fragment Set (BFS) Reconstruction Plates. Significantly lower fatigue resistance was measured for 9* contoured Matta Pelvic System (MPS) Straight Plates compared to 0* contoured plates (p = 0.023). MPS Flex Plates contoured 3* had greater fatigue resistance than 0* contoured (p = 0.031) and 9* contoured plates (p = 0.032). CONCLUSIONS: This work provides fatigue resistance based evidence that clinicians should avoid high repetitions of contouring for MPS Straight Plates. Meanwhile, BFS Reconstruction Plates and MPS Flex Plates are not negatively affected by contouring. These results allow for improved intraoperative decisions about using or discarding plates after multiple contouring repetitions. PMID- 27671527 TI - Development of a Novel Antibody-Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1. AB - T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma), and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody-drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1 expressing cell lines, but not on TIM-1-negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant antitumor activity in a clinically relevant dose range. Safety evaluation in nonhuman primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1-expressing tumors. Mol Cancer Ther; 15(12); 2946-54. (c)2016 AACR. PMID- 27671530 TI - Here come the commensals. PMID- 27671528 TI - Novel ABCG2 Antagonists Reverse Topotecan-Mediated Chemotherapeutic Resistance in Ovarian Carcinoma Xenografts. AB - Chemotherapeutic resistance remains a challenge in the treatment of ovarian carcinoma, especially in recurrent disease. Despite the fact that most patients with newly diagnosed tumors attain complete remission following cytoreductive surgery and chemotherapy, ovarian carcinoma has a recurrence rate that exceeds 75%. The ATP-binding cassette family G member 2 (ABCG2) efflux protein has been described as one mechanism that confers multiple-drug resistance to solid tumors and contributes to topotecan resistance in ovarian carcinoma. In fact, one clinical trial demonstrated ABCG2 expression in all patients with primary or recurrent ovarian carcinoma. On the basis of our previous work, we hypothesized that three compounds (CID44640177, CID1434724, and CID46245505), which represent a new piperazine-substituted pyrazolo[1,5]pyrimidine substructure class of ABCG2 specific antagonists, would restore chemosensitivity to drug-resistant ovarian cancer in vitro and in vivo To address the treatment difficulties associated with chemotherapeutic resistance in ovarian cancer, we combined each compound (CID44640177, CID1434724, and CID46245505) with topotecan and administered the mixture to chemoresistant Igrov1/T8 ovarian cancer cells in vitro and Igrov1/T8 xenografts in CB-17 SCID mice. We found that only nanomolar concentrations of each ABCG2 inhibitor in combination with topotecan were required to restore chemosensitivity to Igrov1/T8 cells in vitro In vivo, substantial tumor reduction was achieved with each compound in 4 days, with CID1434724 causing the largest reduction in excess of 60%. No signs of secondary toxic effects were observed with the ABCG2 antagonists. These novel compounds should be viewed as promising drug candidates to reverse ABCG2-mediated chemoresistance. Mol Cancer Ther; 15(12); 2853-62. (c)2016 AACR. PMID- 27671531 TI - Population genomics of divergence within an obligate pollination mutualism: Selection maintains differences between Joshua tree species. AB - PREMISE OF THE STUDY: Speciation is a complex process that can be shaped by many factors, from geographic isolation to interspecific interactions. In Joshua trees, selection from pollinators on style length has been hypothesized to contribute to the maintenance of differentiation between two hybridizing sister species. We used population genomics approaches to measure the extent of genetic differentiation between these species, test whether selection maintains differences between them, and determine whether genetic variants associated with style length show signatures of selection. METHODS: Using restriction-site associated DNA (RAD)-sequencing, we identified 9516 single nucleotide polymorphisms (SNPs) across the Joshua tree genome. We characterized the genomic composition of trees in a narrow hybrid zone and used genomic scans to search for signatures of selection acting on these SNPs. We used a genome-wide association study to identify SNPs associated with variation in phenotypic traits, including style length, and asked whether those SNPs were overrepresented among the group under selection. KEY RESULTS: The two species were highly genetically differentiated (FST = 0.25), and hybrids were relatively rare in the hybrid zone. Approximately 20% of SNPs showed evidence of selection maintaining divergence. While SNPs associated with style length were overrepresented among those under selection (P << 0.0001), the same was true for SNPs associated with highly differentiated vegetative traits. CONCLUSIONS: The two species of Joshua tree are clearly genetically distinct, and selection is maintaining differences between them. We found that loci associated with differentiated traits were likely to be under selection. However, many traits other than style length appeared to be under selection. Together with the dearth of intermediate hybrids, these findings reveal that these taxa are more strongly diverged than previously suspected and that selection, likely on many targets, is maintaining separation where the two species meet and hybridize. PMID- 27671532 TI - Nitrogen addition does not influence pre-infection partner choice in the legume rhizobium symbiosis. AB - PREMISE OF THE STUDY: Resource mutualisms such as the symbiosis between legumes and nitrogen-fixing rhizobia are context dependent and are sensitive to various aspects of the environment, including nitrogen (N) addition. Mutualist hosts such as legumes are also thought to use mechanisms such as partner choice to discriminate among potential symbionts that vary in partner quality (fitness benefits conferred to hosts) and thus impose selection on rhizobium populations. Together, context dependency and partner choice might help explain why the legume rhizobium mutualism responds evolutionarily to N addition, since plant-mediated selection that shifts in response to N might be expected to favor different rhizobium strains in different N environments. METHODS: We test for the influence of context dependency on partner choice in the model legume, Medicago truncatula, using a factorial experiments with three plant families across three N levels with a mixed inoculation of three rhizobia strains. KEY RESULTS: Neither the relative frequencies of rhizobium strains occupying host nodules, nor the size of those nodules, differed in response to N level. CONCLUSIONS: Despite the lack of context dependence, plant genotypes respond very differently to mixed populations of rhizobia, suggesting that these traits are genetically variable and thus could evolve in response to longer-term increases in N. PMID- 27671533 TI - How old are you? Genet age estimates in a clonal animal. AB - Foundation species such as redwoods, seagrasses and corals are often long-lived and clonal. Genets may consist of hundreds of members (ramets) and originated hundreds to thousands of years ago. As climate change and other stressors exert selection pressure on species, the demography of populations changes. Yet, because size does not indicate age in clonal organisms, demographic models are missing data necessary to predict the resilience of many foundation species. Here, we correlate somatic mutations with genet age of corals and provide the first, preliminary estimates of genet age in a colonial animal. We observed somatic mutations at five microsatellite loci in rangewide samples of the endangered coral, Acropora palmata (n = 3352). Colonies harboured 342 unique mutations in 147 genets. Genet age ranged from 30 to 838 years assuming a mutation rate of 1.195-04 per locus per year based on colony growth rates and 236 to 6500 years assuming a mutation rate of 1.542-05 per locus per year based on sea level changes to habitat availability. Long-lived A. palmata genets imply a large capacity to tolerate past environmental change, and yet recent mass mortality events in A. palmata suggest that capacity is now being frequently exceeded. PMID- 27671534 TI - Health and healthcare access among Zambia's female prisoners: a health systems analysis. AB - BACKGROUND: Research exploring the drivers of health outcomes of women who are in prison in low- and middle-income settings is largely absent. This study aimed to identify and examine the interaction between structural, organisational and relational factors influencing Zambian women prisoners' health and healthcare access. METHODS: We conducted in-depth interviews of 23 female prisoners across four prisons, as well as 21 prison officers and health care workers. The prisoners were selected in a multi-stage sampling design with a purposive selection of prisons followed by a random sampling of cells and of female inmates within cells. Largely inductive thematic analysis was guided by the concepts of dynamic interaction and emergent behaviour, drawn from the theory of complex adaptive systems. RESULTS: We identified compounding and generally negative effects on health and access to healthcare from three factors: i) systemic health resource shortfalls, ii) an implicit prioritization of male prisoners' health needs, and iii) chronic and unchecked patterns of both officer- and inmate-led victimisation. Specifically, women's access to health services was shaped by the interactions between lack of in-house clinics, privileged male prisoner access to limited transport options, and weak responsiveness by female officers to prisoner requests for healthcare. Further intensifying these interactions were prisoners' differential wealth and access to family support, and appointments of senior 'special stage' prisoners which enabled chronic victimisation of less wealthy or less powerful individuals. CONCLUSIONS: This systems-oriented analysis revealed how Zambian women's prisoners' health and access to healthcare is influenced by weak resourcing for prisoner health, administrative biases, and a prevailing organisational and inmate culture. Findings highlight the urgent need for investment in structural improvements in health service availability but also interventions to reform the organisational culture which shapes officers' understanding and responsiveness to women prisoners' health needs. PMID- 27671535 TI - Visit-to-visit systolic blood pressure variability and microvascular complications among patients with diabetes. AB - AIMS: To examine the relationship between systolic blood pressure (SBP) variability and the risk of microvascular complications in a non-elderly diabetic population. METHODS: This is a retrospective cohort study of individuals aged <=60years treated for diabetes in 2003 in the US Department of Veterans Affairs healthcare system. Individuals were followed for five years for any new diagnosis of diabetic nephropathy, retinopathy, or neuropathy. In each year of follow-up, individuals were classified into quartiles based on their SBP variability. RESULTS: We identified 208,338 patients with diabetes without diabetic nephropathy, retinopathy, or neuropathy at baseline. Compared to individuals with the least SBP variability (Quartile 1), those with most variability (Quartile 4) had 81% (OR=1.81; 95% CI, 1.72-1.91), 17% (OR=1.17; 95% CI, 1.13-1.21), 30% (OR=1.30; 95% CI, 1.25-1.35), and 19% (OR=1.19; 95% CI, 1.15-1.23) higher incidence of nephropathy, retinopathy, neuropathy, and any complication, respectively, after adjusting for mean SBP, demographic and clinical factors. CONCLUSIONS: We found a significant graded relationship between SBP variability and the incidence of each complication and of any combined endpoint. This is the first study showing a significant association between SBP variability and the risk of diabetic retinopathy and neuropathy. PMID- 27671536 TI - A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. AB - BACKGROUND: Fifty random genetically unstudied families (limb-girdle muscular dystrophy (LGMD)/myopathy) were screened with a gene panel incorporating 759 OMIM genes associated with neurological disorders. Average coverage of the CDS and 10 bp flanking regions of genes was 99 %. All families were referred to the Neurosciences Clinic of King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Patients presented with muscle weakness affecting the pelvic and shoulder girdle. Muscle biopsy in all cases showed dystrophic or myopathic changes. Our main objective was to evaluate a neurological gene panel as a first line diagnostic test for LGMD/myopathies. RESULTS: Our panel identified the mutation in 76 % of families (38/50; 11 novel). Thirty-four families had mutations in LGMD-related genes with four others having variants not typically associated with LGMD. The majority of cases had recessive inheritance with homoallelic pathogenic variants (97.4 %, 37/38), as expected considering the high rate of consanguinity in the study population. In one case, we detected a heterozygous mutation in DNAJB responsible for LGMD-1E. Our cohort included seven different subtypes of LGMD2. Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1). Whole exome sequencing (WES) of patients who remained undiagnosed with the neurological panel did not improve our diagnostic yield. CONCLUSIONS: Our neurological panel achieved a high clinical sensitivity (76 %) and is an effective first-line laboratory test in patients with LGMD and other myopathies. This sensitive, cost-effective, and rapid assay significantly assists clinical practice especially in these phenotypically and genetically heterogeneous disorders. Moreover, the application of the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines applied in the classification of variant pathogenecity provides a clear interpretation for physicians on the relevance of such findings. PMID- 27671537 TI - Meaning in stroke family caregiving: A literature review. AB - Meaning plays an important role in stroke family caregiving. Understanding meaning facilitates the development of effective interventions that support stroke family caregivers. However, knowledge about this subject is fragmented and sparse. This review fills this knowledge gap by examining existing findings regarding meanings in stroke family caregiving. Specifically, a search of seven databases and a manual search produced a total of five articles for review. Embedded in the lived experience of caregivers, meanings in stroke family caregiving were interpreted as a physical, psychological, and social suffering; an obligation resulting from moral ethics, religion doctrines, others' expectations, and social norms; and a subjective choice based on love, hope, and a sense of reciprocity. However, the detailed process of how and when caregivers identify meaning in caregiving needs further exploration. To gain a full picture of meaning in caregiving, more studies should be conducted among stroke family caregivers from different cultural, economic, and social backgrounds. PMID- 27671538 TI - Against compassion: in defence of a "hybrid" concept of empathy. AB - In this article, I argue that the recent emphasis on compassion in healthcare practice lacks conceptual richness and clarity. In particular, I argue that it would be helpful to focus on a larger concept of empathy rather than compassion alone and that compassion should be thought of as a component of this larger concept of empathy. The first part of the article outlines a critique of the current discourse of compassion on three grounds. This discourse naturalizes, individualizes, and reifies compassion leading to a decontextualized and simplified understanding of failures in healthcare practice. The second part uses resources from phenomenology and contemporary moral philosophy to construct a "hybrid" concept of empathy that includes both pre-reflective/intuitive and cognitive/imaginative components. This "hybrid" concept of empathy leads to a more complex understanding of the multiple responses to others' distress. I conclude that there are no straightforward normative naturalistic responses to others' distress. Rather than conceptualizing compassion as a naturalistic impulse or a character-based trait, we need to consider the complexity of our empathic recognition of vulnerable others. PMID- 27671539 TI - Impact of the introduction of mandatory generic substitution in South Africa: private sector sales of generic and originator medicines for chronic diseases. AB - OBJECTIVE: To assess the impact of mandatory offer of generic substitution, introduced in South Africa in May 2003, on private sector sales of generic and originator medicines for chronic diseases. METHODS: Private sector sales data (June 2001 to May 2005) were obtained from IMS Health for proton pump inhibitors (PPIs; ATC code A02BC), HMG-CoA reductase inhibitors (statins; C10AA), dihydropyridine calcium antagonists (C08CA), angiotensin-converting enzyme inhibitors (ACE-I; C09AA) and selective serotonin reuptake inhibitors (SSRIs; N06AB). Monthly sales were expressed as defined daily doses per 1000 insured population per month (DDD/TIM). Interrupted time-series models were used to estimate the changes in slope and level of medicines use after the policy change. ARIMA models were used to correct for autocorrelation and stationarity. RESULTS: Only the SSRIs saw a significant rise in level of generic utilisation (0.2 DDD/TIM; P < 0.001) and a fall in originator usage (-0.1 DDD/TIM; P < 0.001) after the policy change. Utilisation of generic PPIs fell (level 0.06 DDD/TIM, P = 0.048; slope 0.01 DDD/TIM, P = 0.043), but utilisation of originator products also grew (level 0.05 DDD/TIM, P < 0.001; slope 0.003, P = 0.001). Generic calcium antagonists and ACE-I showed an increase in slope (0.01 DDD/TIM, P = 0.016; 0.02 DDD/TIM, P < 0.001), while the originators showed a decrease in slope (-0.003 DDD/TIM, P = 0.046; -0.01 DDD/TIM, P < 0.001). There were insufficient data on generic statin use before the policy change to allow for analysis. CONCLUSION: The mandatory offer of generic substitution appeared to have had a quantifiable effect on utilisation patterns in the 2 years after May 2003. Managed care interventions that were already in place before the intervention may have blunted the extent of the changes seen in this period. Generic policies are an important enabling provision for cost-containment efforts. However, decisions taken outside of official policy may anticipate or differ from that policy, with important consequences. PMID- 27671541 TI - A Stable Crystalline Triarylphosphine Oxide Radical Anion. AB - Triarylphosphine oxides (Ar3 P=O) are being intensely studied as electron accepting (n-type) materials. Despite the widespread application of these compounds as electron conductors, experimental data regarding the structural and electronic properties of their negatively charged states remain scarce owing to their propensity for follow-up chemistry. Herein, a carefully designed triarylphosphine oxide scaffold is disclosed that comprises sterically demanding spirofluorenyl moieties to shield the central phosphoryl (P=O) moiety. This compound undergoes chemical one-electron reduction to afford an exceptionally stable radical anion, which was isolated and characterized by X-ray crystallography for the very first time. The experimental data, corroborated by computational studies, shall allow for the construction of phosphine oxide materials with enhanced stability. PMID- 27671540 TI - A feasibility study to prevent falls in older people who are sight impaired: the VIP2UK randomised controlled trial. AB - BACKGROUND: Published evaluations of successful interventions to prevent falls in people with sight impairment (SI) are limited. The aim of this feasibility study is to optimise the design and investigation of home safety (HS) and home exercise (HE) programmes to prevent falls in older people with SI. METHODS: A community based feasibility study in north-west England comprising a three-arm randomised controlled trial (RCT) allocated participants to (1) a control group receiving usual care and social visits, (2) an experimental group receiving the HS programme and (3) an experimental group receiving the HS + HE programme. Participants were community-dwelling, aged 65 years and older and sight impaired. Primary outcome data on falls were collected continuously over 6 months. Secondary outcomes on physical activity (self-report and instrumented) and adherence were collected at baseline and 3 and 6 months for HE and at 6 months for the HS programme. Costs for the HS and HS + HE groups were calculated from logs of time spent on home visits, telephone calls and travel. The research assistant and statistician were blinded to group allocation. RESULTS: Altogether, 49 people were recruited over a 9-month period (randomised: 16 to control, 16 to HS, 17 to HS + HE). The interventions were implemented over 6 months by an occupational therapist at a cost per person (pounds sterling, 2011) of L249 (HS) and L674 (HS + HE). Eighty-eight percent (43/49) completed the trial and 6-month follow-up. At 6-month follow-up, 100 % reported partially or completely adhering to HS recommendations but evidence for adherence to HE was equivocal. Although self-reported physical activity increased, instrumented monitoring showed a decrease in walking activity. There were no statistically significant differences in falls between the groups; however, the study was not powered to detect a difference. CONCLUSION: It is feasible and acceptable for an occupational therapist to deliver HS and HE falls prevention programmes to people with SI living independently in the community. Future studies could access Local Authority Registers of people with SI to improve recruitment rates. Further research is required to identify how to improve adherence to HE and to measure changes in physical activity before conducting a definitive RCT. TRIAL REGISTRATION: ISRCTN53433311 , registered on 8 May 2014. PMID- 27671542 TI - Formulation of orodispersible films for paediatric therapy: investigation of feasibility and stability for tetrabenazine as drug model. AB - OBJECTIVES: Orodispersible films (ODF) were formulated to facilitate tetrabenazine (TBZ) administration to paediatric population for the treatment of hyperkinetic movement disorders. METHODS: ODF were obtained by solvent casting/evaporation method using four different polymers (HPMC, PVP, pullulan and HEC). Physicochemical, mechanical and biopharmaceutical characterizations as well as API state in ODF by thermal analysis were investigated to define and compare formulations. ODF stability was also monitored during 6 months to follow evolution of properties. KEY FINDINGS: Analyses at T0 showed few differences between formulations: results of physicochemical and mechanical characterizations were almost similar for each formulation and TBZ appeared at the amorphous state in all cases. ODF delivery system allowed a major improvement of TBZ dissolution profile in buccal conditions compared with pure drug. However, after 3 and 6 months of stability, a TBZ recrystallization occurred for formulations based on PVP and HEC associated with a decrease of drug release in saliva conditions. CONCLUSIONS: HPMC-ODF (F1) appeared as the best formulation. Indeed, physicochemical, mechanical and biopharmaceutical characteristic remained intact. In addition, TBZ remained in amorphous state during stability study. PMID- 27671543 TI - No impact of disease and its treatment on bone mineral density in survivors of childhood acute lymphoblastic leukemia. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) and its treatment are often implicated in adversely affecting bone health. Conflicting reports in the literature and a paucity of studies from the developing world prompted us to study bone mineral density (BMD) in childhood ALL survivors. METHODS: BMD lumbar spine (LS) and whole body (WB) were evaluated, using dual energy x-ray absorptiometry in 65 pediatric ALL survivors who had been off-therapy for at least 2 years. The control group constituted of 50 age- and sex-matched healthy siblings. Kernel density plots were used to compare BMD among cases and controls. The disease-, treatment-, hormone- and lifestyle-related factors likely to modulate BMD were analyzed using the Mann-Whitney U test and Student's t-test. RESULTS: At a median of 4.3 years (range, 2-14.8 years) since cessation of therapy, height-adjusted (HA) mean BMD Z-scores of LS (-0.67 +/- 1.11, -0.607 +/- 1.05, P = 0.759) and WB (-0.842 +/- 0.92, -0.513 +/- 0.97, P = 0.627) were comparable among the cases and controls. Disease, treatment (chemotherapy, cranial radiotherapy) and endocrine factors did not predict low BMD. However, survivors with calcium intake <800 mg/day (WB, P = 0.018) and hypovitaminosis D (<=25 nmol/L) had lower BMD values (HA-WB, P = 0.046) than the controls. A significant proportion of survivors were overweight or obese and had higher BMD Z scores (HA-LS, P = 0.003; HA-WB, P = 0.028). CONCLUSION: BMD Z-scores were similar among ALL survivors and controls. It was reassuring that there was no detrimental impact of the disease or its treatment on BMD. Future studies are required to determine the best possible ways to target the modifiable risk factors (diet, vitamin D) to optimize bone health. PMID- 27671544 TI - Proposed clinical management of pregnancies after combined screening for pre eclampsia at 30-34 weeks' gestation. AB - OBJECTIVE: To estimate the patient-specific risk of pre-eclampsia (PE) at 30-34 weeks' gestation by a combination of maternal characteristics and medical history with multiples of the median (MoM) values of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), and stratify women into high-, intermediate- and low-risk management groups. METHODS: This was a prospective observational study in women attending a third-trimester ultrasound scan at 30-34 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 4 weeks from assessment and at < 40 weeks' gestation were calculated using the competing-risks model to combine the prior risk from maternal characteristics and medical history with MoM values of MAP, UtA-PI, PlGF and sFlt-1. On the basis of these risks, the population was stratified into high , intermediate- and low-risk groups. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category and the performance of screening for delivery with PE at < 4 weeks from assessment and delivery with PE from 4 weeks after assessment and up to 40 weeks' gestation was estimated. RESULTS: The study population of 8128 singleton pregnancies included 234 (2.9%) that subsequently developed PE. Using a risk cut-off of 1 in 50 for PE delivering at < 4 weeks and a risk cut-off of 1 in 150 for PE delivering at < 40 weeks' gestation, the proportion of the population stratified into high, intermediate and low risk was about 3%, 26% and 71%, respectively. The high-risk group contained 90% of pregnancies with PE at < 4 weeks and 40% of those with PE at 4 weeks from assessment to 40 weeks' gestation. The intermediate-risk group contained a further 49% of women with PE at 4 weeks from assessment to 40 gestational weeks. In the low-risk group, none of the women developed PE at < 4 weeks and only 0.3% developed PE at 4 weeks to 40 gestational weeks. CONCLUSION: The study presents risk stratification of PE by the combined test at 30-34 weeks, aiming to identify a high-risk group in need of intensive monitoring from the time of the initial assessment and up to 40 weeks' gestation and an intermediate risk group in need of monitoring from 4 weeks after the initial assessment and up to 40 weeks' gestation. All pregnancies would need to be reassessed at 40 weeks' gestation. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27671545 TI - Alginate therapy is effective treatment for gastroesophageal reflux disease symptoms: a systematic review and meta-analysis. AB - In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some patients, especially those with non-erosive reflux disease or atypical GERD symptoms, acid suppressive therapy with PPIs is not as successful. Alginates are medications that work through an alternative mechanism by displacing the post prandial gastric acid pocket. We performed a systematic review and meta-analysis to examine the benefit of alginate-containing compounds in the treatment of patients with symptoms of GERD.PubMed/MEDLINE, Embase and the Cochrane library electronic databases were searched through October 2015 for randomized controlled trials comparing alginate-containing compounds to placebo, antacids, histamine-2 receptor antagonists (H2RAs) or PPIs for the treatment of GERD symptoms. Additional studies were identified through bibliography review. Non-English studies and those with pediatric patients were excluded. Meta-analyses were performed using random-effects models to calculate odds ratios (OR). Heterogeneity between studies was estimated using the I2 statistic. Analyses were stratified by type of comparator. The search strategy yielded 665 studies and 15 (2.3%) met inclusion criteria. Fourteen were included in the meta-analysis (N = 2095 subjects). Alginate-based therapies increased the odds of resolution of GERD symptoms when compared to placebo or antacids (OR: 4.42; 95% CI 2.45-7.97) with a moderate degree of heterogeneity between studies (I2 = 71%, P = .001). Compared to PPIs or H2RAs, alginates appear less effective but the pooled estimate was not statistically significant (OR: 0.58; 95% CI 0.27-1.22). Alginates are more effective than placebo or antacids for treating GERD symptoms. PMID- 27671546 TI - Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection. AB - Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it's drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine. PMID- 27671547 TI - Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates. AB - BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL 15 consisted in active immunization with structurally modified human IL-15 (mhIL 15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant. RESULTS: Immunization with mhIL-15 elicited a specific antibodies response that neutralized native IL-15-dependent biologic activity in a CTLL-2 cell proliferation assay. The highest neutralizing response was obtained in macaques immunized with mhIL-15 adjuvanted in Alum. This response, which was shown to be transient, also inhibited the activity of simian IL-15 and did not affect the human IL-2-induced proliferation of CTLL-2 cells. Also, in a pool of synovial fluid cells from two Rheumatoid Arthritis patients, the immune sera slightly inhibited TNF-alpha secretion. Finally, it was observed that this vaccine candidate neither affect animal behavior, clinical status, blood biochemistry nor the percentage of IL-15-dependent cell populations, specifically CD56+ NK and CD8+ T cells. CONCLUSION: Our results indicate that vaccination with mhIL-15 induced neutralizing antibodies to native IL-15 in non-human primates. Based on this fact, we propose that this vaccine candidate could be potentially beneficial for treatment of diseases where IL-15 overexpression is associated with their pathogenesis. PMID- 27671549 TI - Tetraphenylcyclopentadiene Derivatives: Aggregation-Induced Emission, Adjustable Luminescence from Green to Blue, Efficient Undoped OLED Performance and Good Mechanochromic Properties. AB - Silole derivatives, the first reported and famous AIEgens, are a series of Si containing conjugated rings with the sigma*-pi* conjugation, and this unique electronic structure imparts them high electron affinity and fast electron mobility, but not ideal blue luminogens due to their relatively long conjugation length. By replacing the Si atom with the C one, six new AIEgens without the sigma*-pi* conjugation effect are successfully synthesized based on a tetraphenylcyclopentadiene core. In addition to the sky-blue emission (lambdaEL = 492 nm) with Lmax , etaC,max , and etaP,max up to 24 096 cd m-2 , 6.80 cd A-1 , and 4.07 lm W-1 , respectively, the careful control of the conjugation degree by changing the linkage mode, results in the blue one (lambdaEL = 440 nm) with relatively good performance (Lmax : 8721 cd m-2 and etaC,max : 3.40 cd A-1 ), indicating that the replacement of the Si atom by C one is an alternative design strategy to yield blue even deep-blue AIEgens with good device performance. Meanwhile, their reversible mechanochromic properties are realized with apparent fluorescence changes between deep-blue and green emissive colors, offering them additional promising applications in optoelectronic devices. PMID- 27671548 TI - Role of the type I tumor necrosis factor receptor in inflammation-associated olfactory dysfunction. AB - BACKGROUND: To understand mechanisms of human olfactory dysfunction in chronic rhinosinusitis, an inducible olfactory inflammation (IOI) model has been utilized to chronically express inflammatory cytokines locally, resulting in neuronal loss, diminished odorant responses, and repressed olfactory regeneration. Knockout of the minor tumor necrosis factor alpha receptor 2 (TNFR2) was previously shown to partially rescue these olfactory changes. The purpose of current study was to investigate the role of the major TNF receptor, TNFR1, in chronic olfactory inflammation. METHODS: Two experimental groups of mice were studied: TNFR1 knockout in IOI background and TNFR1 knockout with allergen induced inflammation. Olfactory function was assayed by electro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. RESULTS: TNF-alpha was dramatically induced in IOI-TNFR1 knockout mice, but the olfactory epithelium did not show inflammation. EOG responses were normal after either 2 or 8 weeks of TNF-alpha expression. Ovalbumin-sensitized TNFR1 knockout mice developed markedly diminished eosinophilic inflammatory infiltration. CONCLUSION: Genetic deletion of TNFR1 completely blocks TNF-alpha induced inflammation and reduces allergen-induced inflammation. Preserved EOG responses suggest a TNFR1-dependent mechanism of TNF-alpha-induced olfactory neuron dysfunction. PMID- 27671550 TI - Is a hybrid strategy a lower-risk alternative to stage 1 Norwood operation? AB - BACKGROUND: For neonates with critical left ventricular outflow tract obstruction (LVOTO), hybrid procedures are an alternative to the Norwood stage 1 procedure. Despite perceived advantages, however, outcomes are not well defined. Therefore, we compared outcomes after stage 1 hybrid and Norwood procedures. METHODS: In a critical LVOTO inception cohort (2005-2014; 20 institutions), a total of 564 neonates underwent stage 1 palliation with the Norwood operation with a modified Blalock-Taussig shunt (NW-BT; n = 232; 41%), Norwood operation with a right ventricle-to-pulmonary artery conduit (NW-RVPA; n = 222; 39%), or a hybrid procedure (n = 110; 20%). Post-stage 1 outcomes were analyzed via competing-risks and parametric hazard analyses and compared among all 564 patients and between patients who underwent propensity-matched hybrid and those who underwent NW-BT/NW RVPA. RESULTS: By 6 years after the stage 1 operation, 50% +/- 3%, 7% +/- 2%, and 4% +/- 1% of patients transitioned to Fontan, transplantation, and biventricular repair, respectively, whereas 7% +/- 2% were alive without transition and 32% +/- 2% died. Risk factors for death without transition included procedure type, smaller ascending aorta, aortic valve atresia, and lower birth weight. Risk adjusted 4-year survival was better after NW-RVPA than after NW-BT or hybrid (76% vs 60% vs 61%; P < .001). Furthermore, for neonates with lower birth weight (<~2 kg), an interaction between birth weight and hybrid resulted in a trend toward better survival after hybrid compared with NW-BT or NW-RVPA. For propensity matched neonates between hybrid and NW-BT (88 pairs), 4-year survival was similar (62% vs 57%; P = .58). For propensity-matched neonates between hybrid and NW-RVPA (81 pairs), 4-year survival was better after NW-RVPA (59% vs 75%; P = .008). CONCLUSIONS: For neonates with critical LVOTO undergoing single-ventricle palliation, NW-RVPA was associated with the best overall survival. Hybrid strategies are not a lower-risk alternative to Norwood operations overall; however, the impact of lower birth weight on survival may be mitigated after hybrid procedures compared with Norwood operations. PMID- 27671551 TI - Structure valve degeneration in new bioprosthesis: New concerns and valve-in valve (VIV) bailout. PMID- 27671552 TI - The hybrid procedure for hypoplastic left heart syndrome: A procedure still looking for its place. PMID- 27671554 TI - A few home truths. AB - There will be those who nod sagely at news that the UKCC is concerned about the number of complaints received about nurses in care homes, particularly in the independent sector. Nurses who find themselves working in this sector, whether by necessity or choice, are olten seen by health service colleagues as a race apart, and a second-class race at that. PMID- 27671553 TI - 18F-FLT Positron Emission Tomography (PET) is a Pharmacodynamic Marker for EWS FLI1 Activity and Ewing Sarcoma. AB - Ewing sarcoma is a bone and soft-tissue tumor that depends on the activity of the EWS-FLI1 transcription factor for cell survival. Although a number of compounds have been shown to inhibit EWS-FLI1 in vitro, a clinical EWS-FLI1-directed therapy has not been achieved. One problem plaguing drug development efforts is the lack of a suitable, non-invasive, pharmacodynamic marker of EWS-FLI1 activity. Here we show that 18F-FLT PET (18F- 3'-deoxy-3'-fluorothymidine positron emission tomography) reflects EWS-FLI1 activity in Ewing sarcoma cells both in vitro and in vivo. 18F-FLT is transported into the cell by ENT1 and ENT2, where it is phosphorylated by TK1 and trapped intracellularly. In this report, we show that silencing of EWS-FLI1 with either siRNA or small-molecule EWS-FLI1 inhibitors suppressed the expression of ENT1, ENT2, and TK1 and thus decreased 18F-FLT PET activity. This effect was not through a generalized loss in viability or metabolic suppression, as there was no suppression of 18F-FDG PET activity and no suppression with chemotherapy. These results provide the basis for the clinical translation of 18F-FLT as a companion biomarker of EWS-FLI1 activity and a novel diagnostic imaging approach for Ewing sarcoma. PMID- 27671556 TI - Care study details. AB - A two-year study by the King's Fund Centre on the introduction of primary nursing to an elderly care ward was published this week. It shows that though patients were no more or less satisfied with the care, more were treated and successfully rehabilitated and fewer died than on two matched wards. PMID- 27671555 TI - UKCC warns of immense' crisis in nursing home sector. AB - The UK is on the brink of a crisis in the nursing home sector that is likely to match the scale of the mental health scandals in the Seventies, the UK Central Council hits warned. PMID- 27671557 TI - DoH drawing up guidelines on local PRP. AB - Guidelines for crusts on the assessment of nursing staff for performance-related pay (PRP) schemes are being drawn up by the Department of Health. PMID- 27671558 TI - ? AB - Blooming success: Sevenoaks nurse Eng-Choo Hitchcock was named Marie Curie Cancer Care Nurse of the Year 1994 at a ceremony in London last week. Mrs Hitchcock, who works for Tunbridge Wells, Maidstone and Bromley health districts, received the award from broadcaster and former nurse Claire Rayner. PMID- 27671559 TI - Welsh office acts to clear 1,250 grading appeals. AB - A new framework for handling the remaining clinical grading appeals in Wales has been set by the Welsh Office. PMID- 27671562 TI - Supervision register leaves gaps in care. AB - Government guidelines on supervision registers for severely mentally ill psychiatric patients, announced last week, have been dismissed as a 'cosmetic PR exercise' by the mental health charity MIND. PMID- 27671561 TI - Scottish prisons shake-up. AB - Proposals for a radical reshaping of prison nursing in Scotland have been accepted by the Scottish Prison Service (SPS). PMID- 27671563 TI - Birmingham aims to shed 1,200 jobs. AB - Hundreds of nurses face redundancy in Birmingham after a health authority announced it is to shed 1,200 staff. PMID- 27671565 TI - ? AB - Helen Betts, MBE, former director of Nursing Services at the Royal Liverpool University Hospital, was one of the contributors to 'Nursing Memories', an eye level history of nursing in Liverpool She Is pieftired with the book, published by National Museums and Galleries of Merseyside at L9.90. PMID- 27671564 TI - Students say P2000 makes better nurses. AB - Project 2000 students believe they will make better nurses than colleagues who are following traditional courses, a government-funded study on the implementation of P2000 reveals. PMID- 27671566 TI - 'Tell women about cancer drug risk'. AB - Women taking the anti-cancer drug Tamoxifen should he told of the risks so they can make informed choices about its use. a leading breast care nurse said last week. Anne Tate, board member of the RCN's Breast Care Nurses' Group, teas commenting on a Dutch study published in The Lancet that suggests a link between the drug and endometrial cancer. Though the study stresses that for women already being treated for breast cancer the benefits of 'Tamoxifen outweigh its possible side-effects, it claims that healthy women who use it to prevent breast cancer could be at risk. But a pilot study at the Royal Marsden Hospital on Tamoxifen's use in healthy women found minimal side-effects. And the UK Co-ordinating Committee on Cancer Research, now running a new study, says the Dutch research shows the risk is lower than expected. PMID- 27671567 TI - Check-ups can reduce use of drugs by elderly people. AB - Nurses who carry out health assessments can reduce elderly people's unnecessary use of drugs, according to a survey published yesterday by the Royal College of Nursing's Daphne Heald Research Unit. PMID- 27671569 TI - Prescription charge rise condemned. AB - The government's move to increase prescription charges has prompted widespread condemnation from health unions. PMID- 27671568 TI - Lords call for greater hospice funding. AB - Quality of life is the bedrock of care for terminally ill patients, the I louse of Lords Select Committee on Medical Ethics decided last week in a report warmly received by nurses and other health care professionals. PMID- 27671570 TI - RCN attacks plan to cut 80 nurse teacher posts. AB - The Royal College of Nursing has attacked plans by the Northern Ireland National Board to axe more than 80 nurse teacher posts over the next three years. PMID- 27671571 TI - Report demands greater public say on health services. AB - A major culture change towards a 'people-centred' health service, with the public allowed to have a real impact on services, is demanded in a report just published. PMID- 27671572 TI - Lothian health chiefs react angrily to unison's charges. AB - Unison's call for a public inquiry into the Lothian acute services strategy has been angrily dismissed by local health chiefs. PMID- 27671575 TI - Mental health nurses' skills training inadequate, says don. AB - Mental health nurses may become 'second best' to other health professionals because post-registration training is not providing them with the appropriate skills, a mental health professor has warned. PMID- 27671573 TI - Unions claim U-turn over skill mix review. AB - Unions arc claiming victory in their fight against a shadow West Midlands trust's plans to axe 50 G-grade community nursing posts. PMID- 27671576 TI - World news. AB - Cyprus The Cypriot health system has been dubbed 'outdated and inefficient', and should be replaced by a national health system, a team of international experts has warned. PMID- 27671577 TI - Conference told patient representatives can give a voice to the vulnerable. AB - Hospital patients think nurses are too busy to bother with their concerns, a conference on patient communication heard last week. Many fear their care will suffer if they raise worries with direct care givers, the Institute of Health Service Management conference heard. PMID- 27671579 TI - Cancer consensus statement. AB - A consensus statement on the cancer care content of pre- registration nurse training has been issued by the Royal College of Nursing. PMID- 27671581 TI - Low blood pressure linked to depression. AB - Older people with low blood pressure are more likely to suffer from fatigue, anorexia, crying spells and depressed moods, a recent study has revealed. PMID- 27671582 TI - Athletes don't benefit from diet supplements. AB - Dietary supplements are unlikely to be of benefit to athletes and are potentially dangerous, Florida researchers caution. PMID- 27671583 TI - Sunbeds and the risk of epidermal dysplasia. AB - Premalignant epidermal dysplasia should be added to the list of side effects of sunbed use, according to Newcastle dermatologists. PMID- 27671585 TI - Extensive sinusitis, asthma and allergy. AB - The associations between chronic sinusitis, asthma and allergy appear to be restricted to people with extensive disease, American researchers say. PMID- 27671584 TI - Small cholesterol drop, big gains for IHD. AB - A modest decrease in serum cholesterol can reduce the risk of ischaemic heart disease by 50 per cent, London researchers report. They analysed data on the incidence of ischaemic heart disease and serum cholesterol concentrations from ten prospective studies, three international studies, and 28 randomised controlled trials. From these they measured the decrease in the incidence of ischaemic heart disease or mortality for a 0.6mmol/ litre (about 10 per cent) decrease in cholesterol. PMID- 27671586 TI - Autoimmune disease and silicone implant link? AB - Can silicone implants induce autoimmune disease in children? New York researchers think it is a possibility. They report two cases where silicone implants had been used as a testicular or scleral prosthesis. Both children, aged 15 and ten, developed systemic lupus erythematosus (SLE). PMID- 27671588 TI - Qualified in caring. AB - The Beverly Allitt tragedy has focused attention on the care of children in hospital in a way that years of lobbying by pressure groups and professional organisations failed to do. PMID- 27671587 TI - More questions than answers. AB - It began with her school days and ended with her arrest. In between, four children died and nine others were attacked. A team of dedicated nurses and doctors were left struggling to comprehend what had happened in their midst and a nation was mortified. Such is the story of Beverly Allitt, as told by Sir Cecil Clothier QC. PMID- 27671589 TI - Corrupted Clothier fits up Allitt staff. AB - The publication of the official report of the Clothier Inquiry into the Beverly Allitt murders has confirmed what a great many of us suspected about the whole affair. PMID- 27671590 TI - Stroke patients in the right places. AB - We read with interest Deidre Wild's article, Stroke: a nursing rehabilitation role (Clinical, January 19). PMID- 27671591 TI - Carry on, chief nursing officer. AB - Why is a nurse in charge of a nursing home designated 'matron', when senior nurses in other areas of the health services have repudiated this title? PMID- 27671592 TI - Limousine bosses play roger the lodger. AB - Student nurses at the North Devon District Hospital, Barnstaple, have now heard of proposals to raise their rents by a massive 127 per cent. PMID- 27671593 TI - Fed up with feminism - withered by women. AB - The anonymous RCN steward's claim (Letters, February 9) that the College is the leader in equality issues, and 'no other organisation has done more for women's issues than the RCN,' leads me to question whether the College really does strive for true sexual equality. PMID- 27671594 TI - ? AB - We welcome all readers' letters but reserve the right to edit them and to withhold names and addresses - either to protect readers or the journal, or both. PMID- 27671595 TI - Information exchange. AB - * I am attempting to devise a lifting/handling risk calculator for use in a palliative care hospice setting, and would value any information which would help with this project. and would value any information which would help with this project. PMID- 27671596 TI - Nightie flight nurse groped in hotel fire. AB - Flu-enforccd bed rest has resulted in my reading every single word of the current Nursing Standard (February 2). I have even read the addresses and locations in the career listings. PMID- 27671597 TI - Susie transmits diseases. AB - Hi there, health care workers. I hope you have your video recorders ready because the first series of the latest fly-on-the-screens hospital documentary is coming soon. PMID- 27671598 TI - Singing in Tune with Time E Cairns Singing in Tune with Time editor Virago/Age Concern 254pp L6.99 1-85381-633-7. AB - As everyone must know by- now, 1993 was the European Year of Older People, and its aims, raising awareness of ageing, challenging ageism and linking the generations, permeate this anthology Singing in Tune with Time: Stories and Poems about Ageing. PMID- 27671600 TI - Health Promotion A Dines and A Cribb Health Promotion editors Blackwell Scientific 210pp L10.99 0-632-03543-9. AB - Health Promotion: Concepts and Practice is written by contributors from the UK and is aimed at those interested in the theory and practice of health promotion and related topics. The book is divided into two parts. PMID- 27671599 TI - Alcohol home detoxification and assessment D Cooper Alcohol home detoxification and assessment Radcliffe Medical 144pp L10.50 1-85775-060-8 [Formula: see text]. AB - Douglas Cameron, senior lecturer in substance misuse at the University of Leicester, wrote the foreword to Alcohol Home Detoxification and Assessment and explains why such a book is necessary. PMID- 27671601 TI - Contrast media reactions. AB - I odinaced contrast media have been an important part of diagnostic radiology for more than 50 years. They are commonly used for imaging in excretion urography of the kidney and for vascular angiography of the myocardium, brain, spinal cord and kidney. Contrast media are classified as ionic or non-ionic. Chemically, conventional ionic media are salts and will create solutions of very high osmolality. Ionic media in iodine concentrations have osmolalities in the range five to seven times greater than the osmolality of blood. PMID- 27671602 TI - Heartlines. AB - Chelation trials The effectiveness of chelation therapy, which addresses the role of calcium in the treatment of arterial disease, has been a somewhat contentious issue. In response to requests from the Arterial Heart Foundation, the British Heart Foundation is looking into the possibility of setting up double-blind trials within centres specialising in chelation therapy. PMID- 27671603 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan Bloodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Fax: 081-423 3867. PMID- 27671605 TI - Fibroblast Growth-factor 23 and Calcium-binding Proteins are not Associated with Chronic Itch in Patients on Haemodialysis. PMID- 27671604 TI - Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis. AB - Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson's trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (alpha-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK 3beta/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity. PMID- 27671607 TI - The Way Ahead. AB - Priorities for creating a community with better mental health. PMID- 27671606 TI - Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process. AB - Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron transfer (SET) process for radical reactions. Representative recent progress includes alpha-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions. PMID- 27671608 TI - Focusing on Individual Needs. AB - Assessment of community care. PMID- 27671609 TI - Wanted: A Job Definition. AB - Examination of the current state of psychiatry and its likely future. PMID- 27671610 TI - Scan. AB - A personal view of the social work scene. PMID- 27671611 TI - From Where I Sit: Editorial Comment. PMID- 27671612 TI - Planning Against Neglect. AB - Proposals for a new service for the elderly. PMID- 27671613 TI - News Review. PMID- 27671614 TI - Swings and Roundabouts. AB - Recognition of the continuing need for 'psychiatric social work' within the context of generically based social services departments. PMID- 27671615 TI - What's on Your Label? AB - Exploration of the way in which 'diagnostic labels' are handicaps in themselves and the way the attachment of a label governs thinking, responding and treatment. PMID- 27671617 TI - The Quiet Revolution. AB - Reflections on the progress, prospects and problems of the voluntary service in mental health movement. PMID- 27671616 TI - Teamwork for the Mentally Handicapped. AB - Proposals for a new, community-based service for the mentally handicapped. PMID- 27671619 TI - Lung Hot Spot Without Corresponding Computed Tomography Abnormality on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Artifactual or Real, Iatrogenic or Pathologic? AB - Focal lung uptake without corresponding lesions or abnormalities on computed tomography (CT) scan poses a dilemma in the interpretation of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). A limited number of case reports have previously suggested an artifactual or iatrogenic nature of the uptake. In the present study, 8 relevant cases were included within a retrospective search of the database. Medical records were reviewed for follow-up radiological and pathologic information. In 7 of 8 cases with focal increased FDG uptake but no corresponding lesions or abnormalities on CT scan, the lung hot spots were artifactual or iatrogenic upon follow-up diagnostic chest CT or repeated PET/CT or both the scans. Microemboli were most likely a potential cause of the pulmonary uptake, with or without partial paravenous injection. One case in the series had a real pulmonary lesion demonstrated on follow-up PET/CT scans and on surgical pathology, although the initial integrated CT and follow-up diagnostic chest CT scans revealed negative findings to demonstrate pulmonary abnormalities corresponding to the hot spot on the PET scan. In conclusion, the finding of a lung hot spot in the absence of anatomical abnormality on FDG PET/CT was most likely artifactual or iatrogenic, but it might also represent a real pulmonary lesion. Nonvisualization of anatomical abnormality could be because of its small size and position directly overlying a segmental vessel. Further image follow-up is necessary and important to clarify the nature of the uptake. PMID- 27671618 TI - Relationship Between Technical Errors and Decision-Making Skills in the Junior Resident. AB - OBJECTIVE: The purpose of this study is to coevaluate resident technical errors and decision-making capabilities during placement of a subclavian central venous catheter (CVC). We hypothesize that there would be significant correlations between scenario-based decision-making skills and technical proficiency in central line insertion. We also predict residents would face problems in anticipating common difficulties and generating solutions associated with line placement. DESIGN: Participants were asked to insert a subclavian central line on a simulator. After completion, residents were presented with a real-life patient photograph depicting CVC placement and asked to anticipate difficulties and generate solutions. Error rates were analyzed using chi-square tests and a 5% expected error rate. Correlations were sought by comparing technical errors and scenario-based decision-making skills. SETTING: This study was performed at 7 tertiary care centers. PARTICIPANTS: Study participants (N = 46) largely consisted of first-year research residents who could be followed longitudinally. Second-year research and clinical residents were not excluded. RESULTS: In total, 6 checklist errors were committed more often than anticipated. Residents committed an average of 1.9 errors, significantly more than the 1 error, at most, per person expected (t(44) = 3.82, p < 0.001). The most common error was performance of the procedure steps in the wrong order (28.5%, p < 0.001). Some of the residents (24%) had no errors, 30% committed 1 error, and 46 % committed more than 1 error. The number of technical errors committed negatively correlated with the total number of commonly identified difficulties and generated solutions (r (33) = -0.429, p = 0.021, r (33) = -0.383, p = 0.044, respectively). CONCLUSIONS: Almost half of the surgical residents committed multiple errors while performing subclavian CVC placement. The correlation between technical errors and decision making skills suggests a critical need to train residents in both technique and error management. PMID- 27671620 TI - Historical colonization and dispersal limitation supplement climate and topography in shaping species richness of African lizards (Reptilia: Agaminae). AB - To what extent deep-time dispersal limitation shapes present-day biodiversity at broad spatial scales remains elusive. Here, we compiled a continental dataset on the distributions of African lizard species in the reptile subfamily Agaminae (a relatively young, Neogene radiation of agamid lizards which ancestors colonized Africa from the Arabian peninsula) and tested to what extent historical colonization and dispersal limitation (i.e. accessibility from areas of geographic origin) can explain present-day species richness relative to current climate, topography, and climate change since the late Miocene (~10 mya), the Pliocene (~3 mya), and the Last Glacial Maximum (LGM, 0.021 mya). Spatial and non spatial multi-predictor regression models revealed that time-limited dispersal via arid corridors is a key predictor to explain macro-scale patterns of species richness. In addition, current precipitation seasonality, current temperature of the warmest month, paleo-temperature changes since the LGM and late Miocene, and topographic relief emerged as important drivers. These results suggest that deep time dispersal constraints - in addition to climate and mountain building - strongly shape current species richness of Africa's arid-adapted taxa. Such historical dispersal limitation might indicate that natural movement rates of species are too slow to respond to rates of ongoing and projected future climate and land use change. PMID- 27671621 TI - Clinical value of the Integrated Pulmonary Index(r) during sedation for interventional upper GI-endoscopy: A randomized, prospective tri-center study. AB - BACKGROUND AND STUDY AIMS: The Integrated Pulmonary Index(r) (IPI) is a mathematically-determined factor based on parameters of capnography and pulse oximetry, which should enable sensitive detection of impaired respiratory function. Aim was to investigate whether an additional measurement of the IPI during sedation for interventional endoscopy, compared to standard monitoring alone, allows a reduction of sedation-related respiratory depression. PATIENTS AND METHODS: 170 patients with standard monitoring randomly underwent either a blinded recording of capnography (control group, n=87) or capnography, including automated IPI calculation (IPI group, n=83), during deep sedation with midazolam and propofol. The primary endpoint was the maximum decrease of oxygen saturation from the baseline level before sedation. Secondary endpoints: incidence of hypoxemia (SaO2<90%), other sedation-related complications (apnea rate, bradycardia, hypotension), patient cooperation and satisfaction (VAS). RESULTS: Mean propofol dose in the IPI group (245+/-61mg) was comparable to the control group (225+/-47mg). The average drop of the oxygen saturation in the IPI group (6.5+/-4.1%) was nearly identical to that of the control group (7.1+/-4.6%, p=0.44). Apnea episodes >15s was found in 46 patients of the control and 31 of the IPI group (p<0.05). Frequency of occurrence of a drop in pO2-saturation <90%, bradycardia <50/min or a drop of systolic pressure <90mmHg were not significantly different in both groups. Mechanical ventilation was not required in any case. Patient cooperation and satisfaction were assessed similar in both groups. CONCLUSION: A clinically appealing advantage of IPI-assessment during deep sedation with midazolam and propofol for interventional endoscopy could not be documented. However, IPI registration was more effective in reducing the incidence of apnea episodes. PMID- 27671622 TI - Association between physical activity and inflammatory bowel disease risk: A meta analysis. AB - BACKGROUND: Previous studies of an association between physical activity and inflammatory bowel disease have yielded conflicting results. AIM: This meta analysis was conducted to clarify whether there is an association between physical activity and inflammatory bowel disease. METHODS: The PubMed and Web of Science databases were searched for relevant studies published up to October 2015. Data were extracted and the summary relative risks (RRs) were calculated using a random effects or a fixed-effects model, according to heterogeneity. RESULTS: Seven studies were included in the analysis. Relative to individuals with low physical activity, those who participated in high physical activity had an RR of 0.63 (95% CI, 0.50-0.79) for developing Crohn's disease. In stratified analyses, a significantly lower risk for Crohn's disease was associated with high physical activity in Europeans only (RR, 0.62; 95% CI, 0.43-0.91); population based control studies (RR, 0.56; 95% CI, 0.41-0.76); and case-control studies (RR, 0.56; 95% CI, 0.41-0.75). The data of 6 studies were pooled to analyze the effect of physical activity on the risk of ulcerative colitis, and no significant association was found (RR, 0.82; 95% CI, 0.68-1.00). CONCLUSIONS: The pooled results of observational studies support that physical activity has a protective effect against Crohn's disease. PMID- 27671623 TI - Low concentrations of bromodichloromethane induce a toxicogenomic response in porcine embryos in vitro. AB - Bromodichloromethane (BDCM) is one of the trihalomethanes present in chlorinated water. Humans are thus daily exposed. Previous contradictory results failed to clearly establish the adverse effects of low concentrations of BDCM. By using the porcine preimplantation embryo as a sensitive model, we showed that exposure to low concentrations of BDCM (10 and 100ppb) during the first week of embryo development induced adverse effect on the blastocyst rate and alteration of the estradiol pathway. Our results also suggest that blastocysts exposed to BDCM present transcriptomic and epigenomic adaptive modifications compatible with the cardiac anomalies observed by previous studies of newborns exposed to BDCM during gestation. Thus, phenotypic observations and toxicogenomic adaptations of embryo to low concentration of BDCM provide insights for BDCM risk assessment. Indeed, our results support the use of sensitive toxicogenomic models using environmentally relevant concentrations to which humans are exposed in order to conduct the risk assessment. PMID- 27671624 TI - Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor. AB - Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis and Huntington's disease. Laquinimod exerts beneficial activities on both the peripheral immune system and the CNS with distinctive changes in CNS resident cell populations, especially astrocytes and microglia. Analysis of genome-wide expression data revealed activation of the aryl hydrocarbon receptor (AhR) pathway in laquinimod treated mice. The AhR pathway modulates the differentiation and function of several cell populations, many of which play an important role in neuroinflammation. We therefore tested the consequences of AhR activation in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) using AhR knockout mice. We demonstrate that the pronounced effect of laquinimod on clinical score, CNS inflammation, and demyelination in EAE was abolished in AhR-/- mice. Furthermore, using bone marrow chimeras we show that deletion of AhR in the immune system fully abrogates, whereas deletion within the CNS partially abrogates the effect of laquinimod in EAE. These data strongly support the idea that AhR is necessary for the efficacy of laquinimod in EAE and that laquinimod may represent a first-in-class drug targeting AhR for the treatment of multiple sclerosis and other neurodegenerative diseases. PMID- 27671625 TI - Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine. AB - The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R+-MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits. PMID- 27671626 TI - New twist on artificial muscles. AB - Lightweight artificial muscle fibers that can match the large tensile stroke of natural muscles have been elusive. In particular, low stroke, limited cycle life, and inefficient energy conversion have combined with high cost and hysteretic performance to restrict practical use. In recent years, a new class of artificial muscles, based on highly twisted fibers, has emerged that can deliver more than 2,000 J/kg of specific work during muscle contraction, compared with just 40 J/kg for natural muscle. Thermally actuated muscles made from ordinary polymer fibers can deliver long-life, hysteresis-free tensile strokes of more than 30% and torsional actuation capable of spinning a paddle at speeds of more than 100,000 rpm. In this perspective, we explore the mechanisms and potential applications of present twisted fiber muscles and the future opportunities and challenges for developing twisted muscles having improved cycle rates, efficiencies, and functionality. We also demonstrate artificial muscle sewing threads and textiles and coiled structures that exhibit nearly unlimited actuation strokes. In addition to robotics and prosthetics, future applications include smart textiles that change breathability in response to temperature and moisture and window shutters that automatically open and close to conserve energy. PMID- 27671627 TI - Testosterone causes both prosocial and antisocial status-enhancing behaviors in human males. AB - Although popular discussion of testosterone's influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status. Here, we tested these hypotheses in healthy young males by injecting testosterone enanthate or a placebo in a double-blind, between subjects, randomized design (n = 40). Participants played a version of the Ultimatum Game that was modified so that, having accepted or rejected an offer from the proposer, participants then had the opportunity to punish or reward the proposer at a proportionate cost to themselves. We found that participants treated with testosterone were more likely to punish the proposer and that higher testosterone levels were specifically associated with increased punishment of proposers who made unfair offers, indicating that testosterone indeed potentiates aggressive responses to provocation. Furthermore, when participants administered testosterone received large offers, they were more likely to reward the proposer and also chose rewards of greater magnitude. This increased generosity in the absence of provocation indicates that testosterone can also cause prosocial behaviors that are appropriate for increasing status. These findings are inconsistent with a simple relationship between testosterone and aggression and provide causal evidence for a more complex role for testosterone in driving status-enhancing behaviors in males. PMID- 27671628 TI - The nature and implications of uniformity in the hierarchical organization of nanomaterials. AB - In this Perspective, we present a framework that defines how to understand and control material structure across length scales with inorganic nanoparticles. Three length scales, frequently discussed separately, are unified under the topic of hierarchical organization: atoms arranged into crystalline nanoparticles, ligands arranged on nanoparticle surfaces, and nanoparticles arranged into crystalline superlattices. Through this lens, we outline one potential pathway toward perfect colloidal matter that emphasizes the concept of uniformity. Uniformity is of both practical and functional importance, necessary to increase structural sophistication and realize the promise of nanostructured materials. Thus, we define the nature of nonuniformity at each length scale as a means to guide ongoing research efforts and highlight potential problems in the field. PMID- 27671629 TI - Grad-seq guides the discovery of ProQ as a major small RNA-binding protein. AB - The functional annotation of transcriptomes and identification of noncoding RNA (ncRNA) classes has been greatly facilitated by the advent of next-generation RNA sequencing which, by reading the nucleotide order of transcripts, theoretically allows the rapid profiling of all transcripts in a cell. However, primary sequence per se is a poor predictor of function, as ncRNAs dramatically vary in length and structure and often lack identifiable motifs. Therefore, to visualize an informative RNA landscape of organisms with potentially new RNA biology that are emerging from microbiome and environmental studies requires the use of more functionally relevant criteria. One such criterion is the association of RNAs with functionally important cognate RNA-binding proteins. Here we analyze the full ensemble of cellular RNAs using gradient profiling by sequencing (Grad-seq) in the bacterial pathogen Salmonella enterica, partitioning its coding and noncoding transcripts based on their network of RNA-protein interactions. In addition to capturing established RNA classes based on their biochemical profiles, the Grad-seq approach enabled the discovery of an overlooked large collective of structured small RNAs that form stable complexes with the conserved protein ProQ. We show that ProQ is an abundant RNA-binding protein with a wide range of ligands and a global influence on Salmonella gene expression. Given its generic ability to chart a functional RNA landscape irrespective of transcript length and sequence diversity, Grad-seq promises to define functional RNA classes and major RNA-binding proteins in both model species and genetically intractable organisms. PMID- 27671630 TI - Humans, water, and the colonization of Australia. AB - The Pleistocene global dispersal of modern humans required the transit of arid and semiarid regions where the distribution of potable water provided a primary constraint on dispersal pathways. Here, we provide a spatially explicit continental-scale assessment of the opportunities for Pleistocene human occupation of Australia, the driest inhabited continent on Earth. We establish the location and connectedness of persistent water in the landscape using the Australian Water Observations from Space dataset combined with the distribution of small permanent water bodies (springs, gnammas, native wells, waterholes, and rockholes). Results demonstrate a high degree of directed landscape connectivity during wet periods and a high density of permanent water points widely but unevenly distributed across the continental interior. A connected network representing the least-cost distance between water bodies and graded according to terrain cost shows that 84% of archaeological sites >30,000 y old are within 20 km of modern permanent water. We further show that multiple, well-watered routes into the semiarid and arid continental interior were available throughout the period of early human occupation. Depletion of high-ranked resources over time in these paleohydrological corridors potentially drove a wave of dispersal farther along well-watered routes to patches with higher foraging returns. PMID- 27671633 TI - Statecraft and expansionary dynamics: A Viru outpost at Huaca Prieta, Chicama Valley, Peru. AB - Interpolity interaction and regional control were central features of all early state societies, taking the form of trade-embedded in political processes to varying degrees-or interregional conquest strategies meant to expand the polity's control or influence over neighboring territories. Cross-cultural analyses of early statecraft suggest that territorial expansion was an integral part of the process of primary state formation, closely associated with the delegation of authority to subordinate administrators and the construction of core outposts of the state in foreign territories. We report here on a potential case of a core outpost, associated with the early Viru state, at the site of Huaca Prieta in the Chicama Valley, located 75 km north of the Viru state heartland on the north coast of Peru. This site is discussed in the context of other possible Viru outposts in the Moche Valley, Pampa La Cruz, and Huaca Las Estrellas, and as part of a broader reflection on expansionary dynamics and statecraft. PMID- 27671631 TI - DNA-dependent homodimerization, sub-cellular partitioning, and protein destabilization control WUSCHEL levels and spatial patterning. AB - The homeodomain transcription factor WUSCHEL (WUS) promotes stem cell maintenance in inflorescence meristems of Arabidopsis thaliana WUS, which is synthesized in the rib meristem, migrates and accumulates at lower levels in adjacent cells. Maintenance of WUS protein levels and spatial patterning distribution is not well understood. Here, we show that the last 63-aa stretch of WUS is necessary for maintaining different levels of WUS protein in the rib meristem and adjacent cells. The 63-aa region contains the following transcriptional regulatory domains: the acidic region, the WUS-box, which is conserved in WUS-related HOMEOBOX family members, and the ethylene-responsive element binding factor associated amphiphilic repression (EAR-like) domain. Our analysis reveals that the opposing functions of WUS-box, which is required for nuclear retention, and EAR-like domain, which participates in nuclear export, are necessary to maintain higher nuclear levels of WUS in cells of the rib meristem and lower nuclear levels in adjacent cells. We also show that the N-terminal DNA binding domain, which is required for both DNA binding and homodimerization, along with the homodimerization sequence located in the central part of the protein, restricts WUS from spreading excessively and show that the homodimerization is critical for WUS function. Our analysis also reveals that a higher level of WUS outside the rib meristem leads to protein destabilization, suggesting a new tier of regulation in WUS protein regulation. Taken together our data show that processes that influence WUS protein levels and spatial distribution are highly coupled to its transcriptional activity. PMID- 27671634 TI - Green and blue water demand from large-scale land acquisitions in Africa. AB - In the last decade, more than 22 million ha of land have been contracted to large scale land acquisitions in Africa, leading to increased pressures, competition, and conflicts over freshwater resources. Currently, 3% of contracted land is in production, for which we model site-specific water demands to indicate where freshwater appropriation might pose high socioenvironmental challenges. We use the dynamic global vegetation model Lund-Potsdam-Jena managed Land to simulate green (precipitation stored in soils and consumed by plants through evapotranspiration) and blue (extracted from rivers, lakes, aquifers, and dams) water demand and crop yields for seven irrigation scenarios, and compare these data with two baseline scenarios of staple crops representing previous water demand. We find that most land acquisitions are planted with crops that demand large volumes of water (>9,000 m3?ha-1) like sugarcane, jatropha, and eucalyptus, and that staple crops have lower water requirements (<7,000 m3?ha-1). Blue water demand varies with irrigation system, crop choice, and climate. Even if the most efficient irrigation systems were implemented, 18% of the land acquisitions, totaling 91,000 ha, would still require more than 50% of water from blue water sources. These hotspots indicate areas at risk for transgressing regional constraints for freshwater use as a result of overconsumption of blue water, where socioenvironmental systems might face increased conflicts and tensions over water resources. PMID- 27671632 TI - Exogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapy. AB - Infection is the single greatest threat to survival during cancer chemotherapy because of depletion of bone marrow-derived immune cells. Phagocytes, especially neutrophils, are key effectors in immunity to extracellular pathogens, which has limited the development of new approaches to protect patients with cancer and chemotherapy-induced neutropenia. Using a model of vaccine-induced protection against lethal Pseudomonas aeruginosa pneumonia in the setting of chemotherapy induced neutropenia, we found a population of resident lung macrophages in the immunized lung that mediated protection in the absence of neutrophils, bone marrow-derived monocytes, or antibodies. These vaccine-induced macrophages (ViMs) expanded after immunization, locally proliferated, and were closely related to alveolar macrophages (AMs) by surface phenotype and gene expression profiles. By contrast to AMs, numbers of ViMs were stable through chemotherapy, showed enhanced phagocytic activity, and prolonged survival of neutropenic mice from lethal P. aeruginosa pneumonia upon intratracheal adoptive transfer. Thus, induction of ViMs by tissue macrophage remodeling may become a framework for new strategies to activate immune-mediated reserves against infection in immunocompromised hosts. PMID- 27671635 TI - Exoplanet orbital eccentricities derived from LAMOST-Kepler analysis. AB - The nearly circular (mean eccentricity [Formula: see text]) and coplanar (mean mutual inclination [Formula: see text]) orbits of the solar system planets motivated Kant and Laplace to hypothesize that planets are formed in disks, which has developed into the widely accepted theory of planet formation. The first several hundred extrasolar planets (mostly Jovian) discovered using the radial velocity (RV) technique are commonly on eccentric orbits ([Formula: see text]). This raises a fundamental question: Are the solar system and its formation special? The Kepler mission has found thousands of transiting planets dominated by sub-Neptunes, but most of their orbital eccentricities remain unknown. By using the precise spectroscopic host star parameters from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) observations, we measure the eccentricity distributions for a large (698) and homogeneous Kepler planet sample with transit duration statistics. Nearly half of the planets are in systems with single transiting planets (singles), whereas the other half are multiple transiting planets (multiples). We find an eccentricity dichotomy: on average, Kepler singles are on eccentric orbits with [Formula: see text] 0.3, whereas the multiples are on nearly circular [Formula: see text] and coplanar [Formula: see text] degree) orbits similar to those of the solar system planets. Our results are consistent with previous studies of smaller samples and individual systems. We also show that Kepler multiples and solar system objects follow a common relation [[Formula: see text](1-2)[Formula: see text]] between mean eccentricities and mutual inclinations. The prevalence of circular orbits and the common relation may imply that the solar system is not so atypical in the galaxy after all. PMID- 27671638 TI - Limited role for methane in the mid-Proterozoic greenhouse. AB - Pervasive anoxia in the subsurface ocean during the Proterozoic may have allowed large fluxes of biogenic CH4 to the atmosphere, enhancing the climatic significance of CH4 early in Earth's history. Indeed, the assumption of elevated pCH4 during the Proterozoic underlies most models for both anomalous climatic stasis during the mid-Proterozoic and extreme climate perturbation during the Neoproterozoic; however, the geologic record cannot directly constrain atmospheric CH4 levels and attendant radiative forcing. Here, we revisit the role of CH4 in Earth's climate system during Proterozoic time. We use an Earth system model to quantify CH4 fluxes from the marine biosphere and to examine the capacity of biogenic CH4 to compensate for the faint young Sun during the "boring billion" years before the emergence of metazoan life. Our calculations demonstrate that anaerobic oxidation of CH4 coupled to SO42- reduction is a highly effective obstacle to CH4 accumulation in the atmosphere, possibly limiting atmospheric pCH4 to less than 10 ppm by volume for the second half of Earth history regardless of atmospheric pO2 If recent pO2 constraints from Cr isotopes are correct, we predict that reduced UV shielding by O3 should further limit pCH4 to very low levels similar to those seen today. Thus, our model results likely limit the potential climate warming by CH4 for the majority of Earth history-possibly reviving the faint young Sun paradox during Proterozoic time and challenging existing models for the initiation of low-latitude glaciation that depend on the oxidative collapse of a steady-state CH4 greenhouse. PMID- 27671636 TI - B7-H1 shapes T-cell-mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity. AB - Molecular mechanisms that determine lesion localization or phenotype variation in multiple sclerosis are mostly unidentified. Although transmigration of activated encephalitogenic T cells across the blood-brain barrier (BBB) is a crucial step in the disease pathogenesis of CNS autoimmunity, the consequences on brain endothelial barrier integrity upon interaction with such T cells and subsequent lesion formation and distribution are largely unknown. We made use of a transgenic spontaneous mouse model of CNS autoimmunity characterized by inflammatory demyelinating lesions confined to optic nerves and spinal cord (OSE mice). Genetic ablation of a single immune-regulatory molecule in this model [i.e., B7-homolog 1 (B7-H1, PD-L1)] not only significantly increased incidence of spontaneous CNS autoimmunity and aggravated disease course, especially in the later stages of disease, but also importantly resulted in encephalitogenic T-cell infiltration and lesion formation in normally unaffected brain regions, such as the cerebrum and cerebellum. Interestingly, B7-H1 ablation on myelin oligodendrocyte glycoprotein-specific CD4+ T cells, but not on antigen-presenting cells, amplified T-cell effector functions, such as IFN-gamma and granzyme B production. Therefore, these T cells were rendered more capable of eliciting cell contact-dependent brain endothelial cell dysfunction and increased barrier permeability in an in vitro model of the BBB. Our findings suggest that a single immune-regulatory molecule on T cells can be ultimately responsible for localized BBB breakdown, and thus substantial changes in lesion topography in the context of CNS autoimmunity. PMID- 27671639 TI - Direct observation of grain rotations during coarsening of a semisolid Al-Cu alloy. AB - Sintering is a key technology for processing ceramic and metallic powders into solid objects of complex geometry, particularly in the burgeoning field of energy storage materials. The modeling of sintering processes, however, has not kept pace with applications. Conventional models, which assume ideal arrangements of constituent powders while ignoring their underlying crystallinity, achieve at best a qualitative description of the rearrangement, densification, and coarsening of powder compacts during thermal processing. Treating a semisolid Al Cu alloy as a model system for late-stage sintering-during which densification plays a subordinate role to coarsening-we have used 3D X-ray diffraction microscopy to track the changes in sample microstructure induced by annealing. The results establish the occurrence of significant particle rotations, driven in part by the dependence of boundary energy on crystallographic misorientation. Evidently, a comprehensive model for sintering must incorporate crystallographic parameters into the thermodynamic driving forces governing microstructural evolution. PMID- 27671637 TI - Adenosine A1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau DeltaK280. AB - Accumulation of Tau is a characteristic hallmark of several neurodegenerative diseases but the mode of toxic action of Tau is poorly understood. Here, we show that the Tau protein is toxic due to its aggregation propensity, whereas phosphorylation and/or missorting is not sufficient to cause neuronal dysfunction. Aggregate-prone Tau accumulates, when expressed in vitro at near endogenous levels, in axons as spindle-shaped grains. These axonal grains contain Tau that is folded in a pathological (MC-1) conformation. Proaggregant Tau induces a reduction of neuronal ATP, concomitant with loss of dendritic spines. Counterintuitively, axonal grains of Tau are not targeted for degradation and do not induce a molecular stress response. Proaggregant Tau causes neuronal and astrocytic hypoactivity and presynaptic dysfunction instead. Here, we show that the adenosine A1 receptor antagonist rolofylline (KW-3902) is alleviating the presynaptic dysfunction and restores neuronal activity as well as dendritic spine levels in vitro. Oral administration of rolofylline for 2-wk to 14-mo-old proaggregant Tau transgenic mice restores the spatial memory deficits and normalizes the basic synaptic transmission. These findings make rolofylline an interesting candidate to combat the hypometabolism and neuronal dysfunction associated with Tau-induced neurodegenerative diseases. PMID- 27671641 TI - Layerless fabrication with continuous liquid interface production. AB - Despite the increasing popularity of 3D printing, also known as additive manufacturing (AM), the technique has not developed beyond the realm of rapid prototyping. This confinement of the field can be attributed to the inherent flaws of layer-by-layer printing and, in particular, anisotropic mechanical properties that depend on print direction, visible by the staircasing surface finish effect. Continuous liquid interface production (CLIP) is an alternative approach to AM that capitalizes on the fundamental principle of oxygen-inhibited photopolymerization to generate a continual liquid interface of uncured resin between the growing part and the exposure window. This interface eliminates the necessity of an iterative layer-by-layer process, allowing for continuous production. Herein we report the advantages of continuous production, specifically the fabrication of layerless parts. These advantages enable the fabrication of large overhangs without the use of supports, reduction of the staircasing effect without compromising fabrication time, and isotropic mechanical properties. Combined, these advantages result in multiple indicators of layerless and monolithic fabrication using CLIP technology. PMID- 27671640 TI - Asymmetric cryo-EM structure of the canonical Allolevivirus Qbeta reveals a single maturation protein and the genomic ssRNA in situ. AB - Single-stranded (ss) RNA viruses infect all domains of life. To date, for most ssRNA virions, only the structures of the capsids and their associated protein components have been resolved to high resolution. Qbeta, an ssRNA phage specific for the conjugative F-pilus, has a T = 3 icosahedral lattice of coat proteins assembled around its 4,217 nucleotides of genomic RNA (gRNA). In the mature virion, the maturation protein, A2, binds to the gRNA and is required for adsorption to the F-pilus. Here, we report the cryo-electron microscopy (cryo-EM) structures of Qbeta with and without symmetry applied. The icosahedral structure, at 3.7-A resolution, resolves loops not previously seen in the published X-ray structure, whereas the asymmetric structure, at 7-A resolution, reveals A2 and the gRNA. A2 contains a bundle of alpha-helices and replaces one dimer of coat proteins at a twofold axis. The helix bundle binds gRNA, causing denser packing of RNA in its proximity, which asymmetrically expands the surrounding coat protein shell to potentially facilitate RNA release during infection. We observe a fixed pattern of gRNA organization among all viral particles, with the major and minor grooves of RNA helices clearly visible. A single layer of RNA directly contacts every copy of the coat protein, with one-third of the interactions occurring at operator-like RNA hairpins. These RNA-coat interactions stabilize the tertiary structure of gRNA within the virion, which could further provide a roadmap for capsid assembly. PMID- 27671642 TI - Neural correlate of the construction of sentence meaning. AB - The neural processes that underlie your ability to read and understand this sentence are unknown. Sentence comprehension occurs very rapidly, and can only be understood at a mechanistic level by discovering the precise sequence of underlying computational and neural events. However, we have no continuous and online neural measure of sentence processing with high spatial and temporal resolution. Here we report just such a measure: intracranial recordings from the surface of the human brain show that neural activity, indexed by gamma-power, increases monotonically over the course of a sentence as people read it. This steady increase in activity is absent when people read and remember nonword lists, despite the higher cognitive demand entailed, ruling out accounts in terms of generic attention, working memory, and cognitive load. Response increases are lower for sentence structure without meaning ("Jabberwocky" sentences) and word meaning without sentence structure (word-lists), showing that this effect is not explained by responses to syntax or word meaning alone. Instead, the full effect is found only for sentences, implicating compositional processes of sentence understanding, a striking and unique feature of human language not shared with animal communication systems. This work opens up new avenues for investigating the sequence of neural events that underlie the construction of linguistic meaning. PMID- 27671643 TI - Morphology and function of Neandertal and modern human ear ossicles. AB - The diminutive middle ear ossicles (malleus, incus, stapes) housed in the tympanic cavity of the temporal bone play an important role in audition. The few known ossicles of Neandertals are distinctly different from those of anatomically modern humans (AMHs), despite the close relationship between both human species. Although not mutually exclusive, these differences may affect hearing capacity or could reflect covariation with the surrounding temporal bone. Until now, detailed comparisons were hampered by the small sample of Neandertal ossicles and the unavailability of methods combining analyses of ossicles with surrounding structures. Here, we present an analysis of the largest sample of Neandertal ossicles to date, including many previously unknown specimens, covering a wide geographic and temporal range. Microcomputed tomography scans and 3D geometric morphometrics were used to quantify shape and functional properties of the ossicles and the tympanic cavity and make comparisons with recent and extinct AMHs as well as African apes. We find striking morphological differences between ossicles of AMHs and Neandertals. Ossicles of both Neandertals and AMHs appear derived compared with the inferred ancestral morphology, albeit in different ways. Brain size increase evolved separately in AMHs and Neandertals, leading to differences in the tympanic cavity and, consequently, the shape and spatial configuration of the ossicles. Despite these different evolutionary trajectories, functional properties of the middle ear of AMHs and Neandertals are largely similar. The relevance of these functionally equivalent solutions is likely to conserve a similar auditory sensitivity level inherited from their last common ancestor. PMID- 27671644 TI - SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury induced SARM1 activation. AB - Axon injury in response to trauma or disease stimulates a self-destruction program that promotes the localized clearance of damaged axon segments. Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is an evolutionarily conserved executioner of this degeneration cascade, also known as Wallerian degeneration; however, the mechanism of SARM1-dependent neuronal destruction is still obscure. SARM1 possesses a TIR domain that is necessary for SARM1 activity. In other proteins, dimerized TIR domains serve as scaffolds for innate immune signaling. In contrast, dimerization of the SARM1 TIR domain promotes consumption of the essential metabolite NAD+ and induces neuronal destruction. This activity is unique to the SARM1 TIR domain, yet the structural elements that enable this activity are unknown. In this study, we identify fundamental properties of the SARM1 TIR domain that promote NAD+ loss and axon degeneration. Dimerization of the TIR domain from the Caenorhabditis elegans SARM1 ortholog TIR-1 leads to NAD+ loss and neuronal death, indicating these activities are an evolutionarily conserved feature of SARM1 function. Detailed analysis of sequence homology identifies canonical TIR motifs as well as a SARM1 specific (SS) loop that are required for NAD+ loss and axon degeneration. Furthermore, we identify a residue in the SARM1 BB loop that is dispensable for TIR activity yet required for injury-induced activation of full-length SARM1, suggesting that SARM1 function requires multidomain interactions. Indeed, we identify a physical interaction between the autoinhibitory N terminus and the TIR domain of SARM1, revealing a previously unrecognized direct connection between these domains that we propose mediates autoinhibition and activation upon injury. PMID- 27671645 TI - Arid5a exacerbates IFN-gamma-mediated septic shock by stabilizing T-bet mRNA. AB - Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a) is an RNA-binding protein that has been shown to play an important immune regulatory function via the stabilization of IL-6 and STAT3 mRNA. However, the role of Arid5a in the overwhelming and uncontrolled immune response that leads to septic shock is unknown. Here, we report that Arid5a-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxic shock and secrete lower levels of major proinflammatory cytokines, including IFN-gamma, IL-6, and TNF-alpha, than WT mice in response to LPS. Arid5a deficiency resulted in decreased levels of IFN gamma under Th1 cell conditions, in which T-box expressed in T cells (T-bet) mRNA expression was inhibited. Arid5a bound to the conserved stem loop structure of the 3'UTR of T-bet and stabilized its mRNA. Arid5a-deficient mice were also resistant to Propionibacterium acnes-primed LPS injection, which is considered to be a T-cell-mediated IFN-gamma dependent endotoxic shock mouse model. Thus, regulation of IFN-gamma by Arid5a via the stabilization of T-bet mRNA in Th1 cells contributes to the development of septic shock in mice. In addition, our previous study suggests that Arid5a control the IL-6 level in vivo in response to LPS by stabilization of IL-6 mRNA. We also observed that neutralization of IFN gamma and IL-6 significantly recovered the mice from endotoxic shock. Taken together, we conclude that Arid5a regulates the augmentation of IL-6 and IFN gamma in response to LPS, which possibly works synergistically for amplification of various other cytokines that ultimately cause the development of septic shock in mice. PMID- 27671646 TI - Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression. AB - Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease. PMID- 27671647 TI - Codon usage is an important determinant of gene expression levels largely through its effects on transcription. AB - Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels. PMID- 27671648 TI - 24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development. AB - Cells in the tumor microenvironment may be reprogrammed by tumor-derived metabolites. Cholesterol-oxidized products, namely oxysterols, have been shown to favor tumor growth directly by promoting tumor cell growth and indirectly by dampening antitumor immune responses. However, the cellular and molecular mechanisms governing oxysterol generation within tumor microenvironments remain elusive. We recently showed that tumor-derived oxysterols recruit neutrophils endowed with protumoral activities, such as neoangiogenesis. Here, we show that hypoxia inducible factor-1a (HIF-1alpha) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol (24S-HC) in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1alpha-24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1+ islets. Pharmacologic blockade or genetic inactivation of oxysterols controls pNET tumorigenesis by dampening the 24S-HC neutrophil axis. Finally, we show that in some human pNET samples Cyp46a1 transcripts are overexpressed, which correlate with the HIF-1alpha target VEGF and with tumor diameter. This study reveals a layer in the angiogenic switch of pNETs and identifies a therapeutic target for pNET patients. PMID- 27671651 TI - Temporally flexible feedback signal to foveal cortex for peripheral object recognition. AB - Recent studies have shown that information from peripherally presented images is present in the human foveal retinotopic cortex, presumably because of feedback signals. We investigated this potential feedback signal by presenting noise in fovea at different object-noise stimulus onset asynchronies (SOAs), whereas subjects performed a discrimination task on peripheral objects. Results revealed a selective impairment of performance when foveal noise was presented at 250-ms SOA, but only for tasks that required comparing objects' spatial details, suggesting a task- and stimulus-dependent foveal processing mechanism. Critically, the temporal window of foveal processing was shifted when mental rotation was required for the peripheral objects, indicating that the foveal retinotopic processing is not automatically engaged at a fixed time following peripheral stimulation; rather, it occurs at a stage when detailed information is required. Moreover, fMRI measurements using multivoxel pattern analysis showed that both image and object category-relevant information of peripheral objects was represented in the foveal cortex. Taken together, our results support the hypothesis of a temporally flexible feedback signal to the foveal retinotopic cortex when discriminating objects in the visual periphery. PMID- 27671649 TI - Keratinocytes contribute intrinsically to psoriasis upon loss of Tnip1 function. AB - Psoriasis is a chronic inflammatory skin disease with a clear genetic contribution, characterized by keratinocyte proliferation and immune cell infiltration. Various closely interacting cell types, including innate immune cells, T cells, and keratinocytes, are known to contribute to inflammation. Innate immune cells most likely initiate the inflammatory process by secretion of IL-23. IL-23 mediates expansion of T helper 17 (Th17) cells, whose effector functions, including IL-17A, activate keratinocytes. Keratinocyte activation in turn results in cell proliferation and chemokine expression, the latter of which fuels the inflammatory process through further immune cell recruitment. One question that remains largely unanswered is how genetic susceptibility contributes to this process and, specifically, which cell type causes disease due to psoriasis-specific genetic alterations. Here we describe a mouse model based on the human psoriasis susceptibility locus TNIP1, also referred to as ABIN1, whose gene product is a negative regulator of various inflammatory signaling pathways, including the Toll-like receptor pathway in innate immune cells. We find that Tnip1-deficient mice recapitulate major features of psoriasis on pathological, genomic, and therapeutic levels. Different genetic approaches, including tissue-specific gene deletion and the use of various inflammatory triggers, reveal that Tnip1 controls not only immune cells, but also keratinocyte biology. Loss of Tnip1 in keratinocytes leads to deregulation of IL-17-induced gene expression and exaggerated chemokine production in vitro and overt psoriasis like inflammation in vivo. Together, the data establish Tnip1 as a critical regulator of IL-17 biology and reveal a causal role of keratinocytes in the pathogenesis of psoriasis. PMID- 27671652 TI - Little evidence for enhanced phenotypic evolution in early teleosts relative to their living fossil sister group. AB - Since Darwin, biologists have been struck by the extraordinary diversity of teleost fishes, particularly in contrast to their closest "living fossil" holostean relatives. Hypothesized drivers of teleost success include innovations in jaw mechanics, reproductive biology and, particularly at present, genomic architecture, yet all scenarios presuppose enhanced phenotypic diversification in teleosts. We test this key assumption by quantifying evolutionary rate and capacity for innovation in size and shape for the first 160 million y (Permian Early Cretaceous) of evolution in neopterygian fishes (the more extensive clade containing teleosts and holosteans). We find that early teleosts do not show enhanced phenotypic evolution relative to holosteans. Instead, holostean rates and innovation often match or can even exceed those of stem-, crown-, and total group teleosts, belying the living fossil reputation of their extant representatives. In addition, we find some evidence for heterogeneity within the teleost lineage. Although stem teleosts excel at discovering new body shapes, early crown-group taxa commonly display higher rates of shape evolution. However, the latter reflects low rates of shape evolution in stem teleosts relative to all other neopterygian taxa, rather than an exceptional feature of early crown teleosts. These results complement those emerging from studies of both extant teleosts as a whole and their sublineages, which generally fail to detect an association between genome duplication and significant shifts in rates of lineage diversification. PMID- 27671650 TI - Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics. AB - The DNA strand exchange protein RAD51 facilitates the central step in homologous recombination, a process fundamentally important for accurate repair of damaged chromosomes, restart of collapsed replication forks, and telomere maintenance. The active form of RAD51 is a nucleoprotein filament that assembles on single stranded DNA (ssDNA) at the sites of DNA damage. The c-Abl tyrosine kinase and its oncogenic counterpart BCR-ABL fusion kinase phosphorylate human RAD51 on tyrosine residues 54 and 315. We combined biochemical reconstitutions of the DNA strand exchange reactions with total internal reflection fluorescence microscopy to determine how the two phosphorylation events affect the biochemical activities of human RAD51 and properties of the RAD51 nucleoprotein filament. By mimicking RAD51 tyrosine phosphorylation with a nonnatural amino acid, p-carboxymethyl-l phenylalanine (pCMF), we demonstrated that Y54 phosphorylation enhances the RAD51 recombinase activity by at least two different mechanisms, modifies the RAD51 nucleoprotein filament formation, and allows RAD51 to compete efficiently with ssDNA binding protein RPA. In contrast, Y315 phosphorylation has little effect on the RAD51 activities. Based on our work and previous cellular studies, we propose a mechanism underlying RAD51 activation by c-Abl/BCR-ABL kinases. PMID- 27671653 TI - Threshold-dependent transcriptional discrimination underlies stem cell homeostasis. AB - Transcriptional mechanisms that underlie the dose-dependent regulation of gene expression in animal development have been studied extensively. However, the mechanisms of dose-dependent transcriptional regulation in plant development have not been understood. In Arabidopsis shoot apical meristems, WUSCHEL (WUS), a stem cell-promoting transcription factor, accumulates at a higher level in the rib meristem and at a lower level in the central zone where it activates its own negative regulator, CLAVATA3 (CLV3). How WUS regulates CLV3 levels has not been understood. Here we show that WUS binds a group of cis-elements, cis- regulatory module, in the CLV3-regulatory region, with different affinities and conformations, consisting of monomers at lower concentration and as dimers at a higher level. By deleting cis elements, manipulating the WUS-binding affinity and the homodimerization threshold of cis elements, and manipulating WUS levels, we show that the same cis elements mediate both the activation and repression of CLV3 at lower and higher WUS levels, respectively. The concentration-dependent transcriptional discrimination provides a mechanistic framework to explain the regulation of CLV3 levels that is critical for stem cell homeostasis. PMID- 27671654 TI - Nanokit for single-cell electrochemical analyses. AB - The development of more intricate devices for the analysis of small molecules and protein activity in single cells would advance our knowledge of cellular heterogeneity and signaling cascades. Therefore, in this study, a nanokit was produced by filling a nanometer-sized capillary with a ring electrode at the tip with components from traditional kits, which could be egressed outside the capillary by electrochemical pumping. At the tip, femtoliter amounts of the kit components were reacted with the analyte to generate hydrogen peroxide for the electrochemical measurement by the ring electrode. Taking advantage of the nanotip and small volume injection, the nanokit was easily inserted into a single cell to determine the intracellular glucose levels and sphingomyelinase (SMase) activity, which had rarely been achieved. High cellular heterogeneities of these two molecules were observed, showing the significance of the nanokit. Compared with the current methods that use a complicated structural design or surface functionalization for the recognition of the analytes, the nanokit has adapted features of the well-established kits and integrated the kit components and detector in one nanometer-sized capillary, which provides a specific device to characterize the reactivity and concentrations of cellular compounds in single cells. PMID- 27671655 TI - RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. AB - The tight spatial coupling of synaptic vesicles and voltage-gated Ca2+ channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM BPs) interact with Ca2+ channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2-deficient murine hippocampal neurons in cultures and slices. Short-term facilitation is significantly enhanced in both model systems. Detailed analysis in culture revealed a reduction in initial release probability, which presumably underlies the increased short-term facilitation. Superresolution microscopy revealed an impairment in CaV2.1 clustering at AZs, which likely alters Ca2+ nanodomains at release sites and thereby affects release probability. Additional deletion of RIM-BP1 does not exacerbate the phenotype, indicating that RIM-BP2 is the dominating RIM-BP isoform at these synapses. PMID- 27671656 TI - Trisaccharide containing alpha2,3-linked sialic acid is a receptor for mumps virus. AB - Mumps virus (MuV) remains an important pathogen worldwide, causing epidemic parotitis, orchitis, meningitis, and encephalitis. Here we show that MuV preferentially uses a trisaccharide containing alpha2,3-linked sialic acid in unbranched sugar chains as a receptor. Crystal structures of the MuV attachment protein hemagglutinin-neuraminidase (MuV-HN) alone and in complex with the alpha2,3-sialylated trisaccharide revealed that in addition to the interaction between the MuV-HN active site residues and sialic acid, other residues, including an aromatic residue, stabilize the third sugar of the trisaccharide. The importance of the aromatic residue and the third sugar in the MuV-HN-receptor interaction was confirmed by computational energy calculations, isothermal titration calorimetry studies, and glycan-binding assays. Furthermore, MuV-HN was found to bind more efficiently to unbranched alpha2,3-sialylated sugar chains compared with branched ones. Importantly, the strategically located aromatic residue is conserved among the HN proteins of sialic acid-using paramyxoviruses, and alanine substitution compromised their ability to support cell-cell fusion. These results suggest that not only the terminal sialic acid but also the adjacent sugar moiety contribute to receptor function for mumps and these paramyxoviruses. The distribution of structurally different sialylated glycans in tissues and organs may explain in part MuV's distinct tropism to glandular tissues and the central nervous system. In the crystal structure, the epitopes for neutralizing antibodies are located around the alpha-helices of MuV-HN that are not well conserved in amino acid sequences among different genotypes of MuV. This may explain the fact that MuV reinfection sometimes occurs. PMID- 27671658 TI - Shape-programmable magnetic soft matter. AB - Shape-programmable matter is a class of active materials whose geometry can be controlled to potentially achieve mechanical functionalities beyond those of traditional machines. Among these materials, magnetically actuated matter is particularly promising for achieving complex time-varying shapes at small scale (overall dimensions smaller than 1 cm). However, previous work can only program these materials for limited applications, as they rely solely on human intuition to approximate the required magnetization profile and actuating magnetic fields for their materials. Here, we propose a universal programming methodology that can automatically generate the required magnetization profile and actuating fields for soft matter to achieve new time-varying shapes. The universality of the proposed method can therefore inspire a vast number of miniature soft devices that are critical in robotics, smart engineering surfaces and materials, and biomedical devices. Our proposed method includes theoretical formulations, computational strategies, and fabrication procedures for programming magnetic soft matter. The presented theory and computational method are universal for programming 2D or 3D time-varying shapes, whereas the fabrication technique is generic only for creating planar beams. Based on the proposed programming method, we created a jellyfish-like robot, a spermatozoid-like undulating swimmer, and an artificial cilium that could mimic the complex beating patterns of its biological counterpart. PMID- 27671659 TI - Multiplicity of morphologies in poly (l-lactide) bioresorbable vascular scaffolds. AB - Poly(l-lactide) (PLLA) is the structural material of the first clinically approved bioresorbable vascular scaffold (BVS), a promising alternative to permanent metal stents for treatment of coronary heart disease. BVSs are transient implants that support the occluded artery for 6 mo and are completely resorbed in 2 y. Clinical trials of BVSs report restoration of arterial vasomotion and elimination of serious complications such as late stent thrombosis. It is remarkable that a scaffold made from PLLA, known as a brittle polymer, does not fracture when crimped onto a balloon catheter or during deployment in the artery. We used X-ray microdiffraction to discover how PLLA acquired ductile character and found that the crimping process creates localized regions of extreme anisotropy; PLLA chains in the scaffold change orientation from the hoop direction to the radial direction on micrometer-scale distances. This multiplicity of morphologies in the crimped scaffold works in tandem to enable a low-stress response during deployment, which avoids fracture of the PLLA hoops and leaves them with the strength needed to support the artery. Thus, the transformations of the semicrystalline PLLA microstructure during crimping explain the unexpected strength and ductility of the current BVS and point the way to thinner resorbable scaffolds in the future. PMID- 27671657 TI - Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis. AB - The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1). In contrast, the athero protective laminar flow suppressed YAP/TAZ activities. En face analysis of mouse arteries demonstrated an increased nuclear localization of YAP/TAZ and elevated levels of the target genes in the endothelium in atheroprone areas compared with athero-protective areas. YAP/TAZ knockdown significantly attenuated the disturbed flow induction of EC proliferative and proinflammatory phenotypes, whereas overexpression of constitutively active YAP was sufficient to promote EC proliferation and inflammation. In addition, treatment with statin, an antiatherosclerotic drug, inhibited YAP/TAZ activities to diminish the disturbed flow-induced proliferation and inflammation. In vivo blockade of YAP/TAZ translation by morpholino oligos significantly reduced endothelial inflammation and the size of atherosclerotic lesions. Our results demonstrate a critical role of the activation of YAP/TAZ by disturbed flow in promoting atheroprone phenotypes and atherosclerotic lesion development. Therefore, inhibition of YAP/TAZ activation is a promising athero-protective therapeutic strategy. PMID- 27671661 TI - Pallidal spiking activity reflects learning dynamics and predicts performance. AB - The basal ganglia (BG) network has been divided into interacting actor and critic components, modulating the probabilities of different state-action combinations through learning. Most models of learning and decision making in the BG focus on the roles of the striatum and its dopaminergic inputs, commonly overlooking the complexities and interactions of BG downstream nuclei. In this study, we aimed to reveal the learning-related activity of the external segment of the globus pallidus (GPe), a downstream structure whose computational role has remained relatively unexplored. Recording from monkeys engaged in a deterministic three choice reversal learning task, we found that changes in GPe discharge rates predicted subsequent behavioral shifts on a trial-by-trial basis. Furthermore, the activity following the shift encoded whether it resulted in reward or not. The frequent changes in stimulus-outcome contingencies (i.e., reversals) allowed us to examine the learning-related neural activity and show that GPe discharge rates closely matched across-trial learning dynamics. Additionally, firing rates exhibited a linear decrease in sequences of correct responses, possibly reflecting a gradual shift from goal-directed execution to automaticity. Thus, modulations in GPe spiking activity are highest for attention-demanding aspects of behavior (i.e., switching choices) and decrease as attentional demands decline (i.e., as performance becomes automatic). These findings are contrasted with results from striatal tonically active neurons, which show none of these task related modulations. Our results demonstrate that GPe, commonly studied in motor contexts, takes part in cognitive functions, in which movement plays a marginal role. PMID- 27671660 TI - Mitochondrial DNA from the eradicated European Plasmodium vivax and P. falciparum from 70-year-old slides from the Ebro Delta in Spain. AB - Phylogenetic analysis of Plasmodium parasites has indicated that their modern-day distribution is a result of a series of human-mediated dispersals involving transport between Africa, Europe, America, and Asia. A major outstanding question is the phylogenetic affinity of the malaria causing parasites Plasmodium vivax and falciparum in historic southern Europe-where it was endemic until the mid 20th century, after which it was eradicated across the region. Resolving the identity of these parasites will be critical for answering several hypotheses on the malaria dispersal. Recently, a set of slides with blood stains of malaria affected people from the Ebro Delta (Spain), dated between 1942 and 1944, have been found in a local medical collection. We extracted DNA from three slides, two of them stained with Giemsa (on which Plasmodium parasites could still be seen under the microscope) and another one consisting of dried blood spots. We generated the data using Illumina sequencing after using several strategies aimed at increasing the Plasmodium DNA yield: depletion of the human genomic (g)DNA content through hybridization with human gDNA baits, and capture-enrichment using gDNA derived from P. falciparum Plasmodium mitochondrial genome sequences were subsequently reconstructed from the resulting data. Phylogenetic analysis of the eradicated European P. vivax mtDNA genome indicates that the European isolate is closely related to the most common present-day American haplotype and likely entered the American continent post-Columbian contact. Furthermore, the European P. falciparum mtDNA indicates a link with current Indian strains that is in agreement with historical accounts. PMID- 27671663 TI - Consistency of dementia caregiver intervention classification: an evidence-based synthesis. AB - BACKGROUND: There are many systematic reviews and meta-analyses (SRs) of interventions for family caregivers of persons with Alzheimer's disease or a related dementia. A challenge when synthesizing the efficacy of dementia caregiver interventions is the potential discrepancy in how they are categorized. The objective of this study was to systematically examine inconsistencies in how dementia caregiver interventions are classified. METHODS: We searched Ovid Medline(r), Ovid PsycINFO(r), Ovid Embase(r), and the Cochrane Library to identify previous SRs published and indexed in bibliographic databases through January 2015. Following a graphical network analysis, open-coding of classification definitions was conducted. A descriptive analysis was then completed to examine classification consistency of individual interventions across SR grouping labels. RESULTS: Twenty-three SRs were identified. A graphical network analysis revealed a significant amount of overlap in individual studies included across SRs, but stark differences in how reviews labeled or categorized them. The qualitative content analysis identified seven themes; one of these, content of the intervention, was used to compare classification consistency. When subjecting the classification of interventions to descriptive empirical analysis, extensive inconsistency was apparent. CONCLUSIONS: The substantial inconsistency in how dementia caregiver interventions are classified across SRs has hindered the science and practice of dementia caregiver interventions. Specifically, accurate reporting of intervention components and SRs would allow for more precise assessments of efficacy as well as a fuller determination of how caregiver interventions can best yield benefits for caregivers and persons with dementia. PMID- 27671662 TI - Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome. AB - Connectome genetics seeks to uncover how genetic factors shape brain functional connectivity; however, the causal impact of a single gene's activity on whole brain networks remains unknown. We tested whether the sole targeted deletion of the mu opioid receptor gene (Oprm1) alters the brain connectome in living mice. Hypothesis-free analysis of combined resting-state fMRI diffusion tractography showed pronounced modifications of functional connectivity with only minor changes in structural pathways. Fine-grained resting-state fMRI mapping, graph theory, and intergroup comparison revealed Oprm1-specific hubs and captured a unique Oprm1 gene-to-network signature. Strongest perturbations occurred in connectional patterns of pain/aversion-related nodes, including the mu receptor enriched habenula node. Our data demonstrate that the main receptor for morphine predominantly shapes the so-called reward/aversion circuitry, with major influence on negative affect centers. PMID- 27671664 TI - Urban design and transport to promote healthy lives. PMID- 27671665 TI - Healthier neighbourhoods through healthier parks. PMID- 27671666 TI - Urban design: an important future force for health and wellbeing. PMID- 27671667 TI - A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. PMID- 27671668 TI - City planning and population health: a global challenge. AB - Significant global health challenges are being confronted in the 21st century, prompting calls to rethink approaches to disease prevention. A key part of the solution is city planning that reduces non-communicable diseases and road trauma while also managing rapid urbanisation. This Series of papers considers the health impacts of city planning through transport mode choices. In this, the first paper, we identify eight integrated regional and local interventions that, when combined, encourage walking, cycling, and public transport use, while reducing private motor vehicle use. These interventions are destination accessibility, equitable distribution of employment across cities, managing demand by reducing the availability and increasing the cost of parking, designing pedestrian-friendly and cycling-friendly movement networks, achieving optimum levels of residential density, reducing distance to public transport, and enhancing the desirability of active travel modes (eg, creating safe attractive neighbourhoods and safe, affordable, and convenient public transport). Together, these interventions will create healthier and more sustainable compact cities that reduce the environmental, social, and behavioural risk factors that affect lifestyle choices, levels of traffic, environmental pollution, noise, and crime. The health sector, including health ministers, must lead in advocating for integrated multisector city planning that prioritises health, sustainability, and liveability outcomes, particularly in rapidly changing low-income and middle income countries. We recommend establishing a set of indicators to benchmark and monitor progress towards achievement of more compact cities that promote health and reduce health inequities. PMID- 27671669 TI - Mark Stevenson: systems thinker for cities. PMID- 27671670 TI - Use of science to guide city planning policy and practice: how to achieve healthy and sustainable future cities. AB - Land-use and transport policies contribute to worldwide epidemics of injuries and non-communicable diseases through traffic exposure, noise, air pollution, social isolation, low physical activity, and sedentary behaviours. Motorised transport is a major cause of the greenhouse gas emissions that are threatening human health. Urban and transport planning and urban design policies in many cities do not reflect the accumulating evidence that, if policies would take health effects into account, they could benefit a wide range of common health problems. Enhanced research translation to increase the influence of health research on urban and transport planning decisions could address many global health problems. This paper illustrates the potential for such change by presenting conceptual models and case studies of research translation applied to urban and transport planning and urban design. The primary recommendation of this paper is for cities to actively pursue compact and mixed-use urban designs that encourage a transport modal shift away from private motor vehicles towards walking, cycling, and public transport. This Series concludes by urging a systematic approach to city design to enhance health and sustainability through active transport and a move towards new urban mobility. Such an approach promises to be a powerful strategy for improvements in population health on a permanent basis. PMID- 27671672 TI - TAK1 knockdown enhances lipopolysaccharide-induced secretion of proinflammatory cytokines in myeloid cells via unleashing MEKK3 activity. AB - TGF-beta activating protein kinase 1 (TAK1) belongs to the MAP kinase kinase kinase (MAP3K) family. TAK1 is involved in many signaling pathways, especially the innate and adaptive immune responses. TAK1 mediates nuclear factor kappaB (NF kappaB) and MAPK signaling pathway in response to interleukin-1, tumor necrosis factor-alpha (TNFalpha), and toll-like receptor agonists, such as lipopolysaccharide (LPS). The regulatory roles of TAK1 in LPS-induced proinflammatory cytokines production are dependent on the cell types. In this study, we examined the effects of TAK1 on the LPS induced production of proinflammatory cytokines in myeloid cells. Knockdown of TAK1 enhanced the secretion of interleukin 1-beta (IL-1beta) and TNFalpha induced by LPS. In addition, LPS-activated TAK1 negatively regulates mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3). Moreover, TAK1 inhibited MEKK3 activation, which, in turn, activated NF-kappaB. These results indicate that TAK1 negatively regulates LPS-induced cytokine secretion in myeloid cells by inhibiting MEKK3 activities. PMID- 27671671 TI - Land use, transport, and population health: estimating the health benefits of compact cities. AB - Using a health impact assessment framework, we estimated the population health effects arising from alternative land-use and transport policy initiatives in six cities. Land-use changes were modelled to reflect a compact city in which land use density and diversity were increased and distances to public transport were reduced to produce low motorised mobility, namely a modal shift from private motor vehicles to walking, cycling, and public transport. The modelled compact city scenario resulted in health gains for all cities (for diabetes, cardiovascular disease, and respiratory disease) with overall health gains of 420 826 disability-adjusted life-years (DALYs) per 100 000 population. However, for moderate to highly motorised cities, such as Melbourne, London, and Boston, the compact city scenario predicted a small increase in road trauma for cyclists and pedestrians (health loss of between 34 and 41 DALYs per 100 000 population). The findings suggest that government policies need to actively pursue land-use elements-particularly a focus towards compact cities-that support a modal shift away from private motor vehicles towards walking, cycling, and low-emission public transport. At the same time, these policies need to ensure the provision of safe walking and cycling infrastructure. The findings highlight the opportunities for policy makers to positively influence the overall health of city populations. PMID- 27671673 TI - Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant. AB - STUDY QUESTION: Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? SUMMARY ANSWER: The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. WHAT IS KNOWN ALREADY: The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. STUDY DESIGN SIZE, DURATION: For the first 3 years, this study was an open-label, multi centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan-Meier (K-M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non users of hormonal contraceptive method for comparative purposes. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K-M cumulative pregnancy rates for ENG- and LNG implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2 1.8] and 0.8 per 100 W-Y [95% CI: 0.2-2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more likely than LNG-users to experience heavy bleeding (p < 0.05). The median duration of the implant removal procedure was 64 seconds shorter for the one-rod ENG-implant (inter-quartile range (IQR) = 30.5, 117.5) compared to the two-rod LNG product (IQR = 77.0, 180.0). The 2-year rate for pregnancy in the IUD group compared with the two implant groups combined was 4.1 per 100 W-Y [95% CI: 2.5-6.5]. LIMITATIONS, REASONS FOR CAUTION: Few women were <=19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women >=70 kg were few. WIDER IMPLICATIONS OF THE FINDINGS: The results from this study corroborate previous evidence showing high contraceptive efficacy through 4 years for the ENG-implant. Data through 5 years are a novel contribution and further proof of the product's capability to provide safe and effective contraception that rivals the current 5-year LNG-subdermal implant. The findings provide valuable information for policy makers, family planning programmers and clinicians that the ENG-releasing subdermal implant is still highly effective up to 5 years after insertion. Compared to previous efforts, our study population was geographically diverse and our study had the highest number of participants completing at least 5 years of use. TRIAL REGISTRATION: The trial was registered as ISRCTN33378571. STUDY FUNDING/COMPETING INTERESTS: The contraceptive devices and funds for conduct of the study were provided by the United Nations Development Programme/United Nations Population Fund/World Health Organization (WHO)/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), WHO. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the WHO. All stated authors have no conflict of interest, except Dr Hubacher who reported grants from United States Agency for International Development, during the conduct of the study; other from Advisory Boards (Teva, Bayer, OCON), outside the submitted work. PMID- 27671674 TI - Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and Autophagy in Ovarian Cancer and Melanoma. AB - PD-L1 antibodies produce efficacious clinical responses in diverse human cancers, but the basis for their effects remains unclear, leaving a gap in the understanding of how to rationally leverage therapeutic activity. PD-L1 is widely expressed in tumor cells, but its contributions to tumor pathogenicity are incompletely understood. In this study, we evaluated the hypothesis that PD-L1 exerts tumor cell-intrinsic signals that are critical for pathogenesis. Using RNAi methodology, we attenuated PD-L1 in the murine ovarian cell line ID8agg and the melanoma cell line B16 (termed PD-L1lo cells), which express basal PD-L1. We observed that PD-L1lo cells proliferated more weakly than control cells in vitro As expected, PD-L1lo cells formed tumors in immunocompetent mice relatively more slowly, but unexpectedly, they also formed tumors more slowly in immunodeficient NSG mice. RNA sequencing analysis identified a number of genes involved in autophagy and mTOR signaling that were affected by PD-L1 expression. In support of a functional role, PD-L1 attenuation augmented autophagy and blunted the ability of autophagy inhibitors to limit proliferation in vitro and in vivo in NSG mice. PD-L1 attenuation also reduced mTORC1 activity and augmented the antiproliferative effects of the mTORC1 inhibitor rapamycin. PD-L1lo cells were also relatively deficient in metastasis to the lung, and we found that anti-PD-L1 administration could block tumor cell growth and metastasis in NSG mice. This therapeutic effect was observed with B16 cells but not ID8agg cells, illustrating tumor- or compartmental-specific effects in the therapeutic setting. Overall, our findings extend understanding of PD-L1 functions, illustrate nonimmune effects of anti-PD-L1 immunotherapy, and suggest broader uses for PD-L1 as a biomarker for assessing cancer therapeutic responses. Cancer Res; 76(23); 6964-74. (c)2016 AACR. PMID- 27671675 TI - FGF2 from Marrow Microenvironment Promotes Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia. AB - Potent FLT3 inhibitors, such as quizartinib (AC220), have shown promise in treating acute myeloid leukemia (AML) containing FLT3 internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of resistance whereby extrinsic microenvironmental proteins FLT3 ligand (FL) and fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation of ligand-independent resistance mechanisms. FL directly attenuated AC220 inhibition of FLT3, consistent with previous reports. Conversely, FGF2 promoted resistance through activation of FGFR1 and downstream MAPK effectors; these resistant cells responded synergistically to combinatorial inhibition of FGFR1 and FLT3. Removing FL or FGF2 from ligand-dependent resistant cultures transiently restored sensitivity to AC220, but accelerated acquisition of secondary resistance via reactivation of FLT3 and RAS/MAPK signaling. FLT3-ITD AML patients treated with AC220 developed increased FGF2 expression in marrow stromal cells, which peaked prior to overt clinical relapse and detection of resistance mutations. Overall, these results support a strategy of early combination therapy to target early survival signals from the bone marrow microenvironment, in particular FGF2, to improve the depth of response in FLT3 ITD AML. Cancer Res; 76(22); 6471-82. (c)2016 AACR. PMID- 27671676 TI - Modulation of Immune Checkpoints and Graft-versus-Leukemia in Allogeneic Transplants by Antagonizing Vasoactive Intestinal Peptide Signaling. AB - The goal of allogeneic bone marrow transplantation (allo-BMT) is elimination of leukemia cells through the graft-versus-leukemia (GvL) activity of donor cells, while limiting graft-versus-host disease (GvHD). Immune checkpoint pathways regulate GvL and GvHD activities, but blocking antibodies or genetic inactivation of these pathways can cause lethal GVHD. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide that regulates coinhibitory pathways; its role in allo-BMT has not been studied. We found VIP transiently expressed in donor NK, NK-T, dendritic cells, and T cells after allo transplant, as well as host leukocytes. A peptide antagonist of VIP signaling (VIPhyb) increased T-cell proliferation in vitro and reduced IL10 expression in donor T cells. Treatment of allo-BMT recipients with VIPhyb, or transplanting donor grafts lacking VIP (VIP KO), activated donor T-cells in lymphoid organs, reduced T-cell homing to GvHD target organs, and enhanced GvL without increasing GvHD in multiple allo-BMT models. Genetic or ex vivo depletion of donor NK cells or CD8+ T cells from allografts abrogated the VIPhyb-enhanced GvL activity. VIPhyb treatment led to downregulation of PD-1 and PD-L1 expression on donor immune cells, increased effector molecule expression, and expanded oligoclonal CD8+ T cells that protected secondary allo transplant recipients from leukemia. Blocking VIP signaling thus represents a novel pharmacologic approach to separate GvL from GvHD and enhance adaptive T-cell responses to leukemia-associated antigens in allo-BMT. Cancer Res; 76(23); 6802-15. (c)2016 AACR. PMID- 27671677 TI - SPINK6 Promotes Metastasis of Nasopharyngeal Carcinoma via Binding and Activation of Epithelial Growth Factor Receptor. AB - Nasopharyngeal carcinoma has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. The underlying molecular mechanisms of nasopharyngeal carcinoma metastasis are not fully understood. Here, we report the identification of serine protease inhibitor Kazal-type 6 (SPINK6) as a functional regulator of nasopharyngeal carcinoma metastasis via EGFR signaling. SPINK6 mRNA was upregulated in tumor and highly metastatic nasopharyngeal carcinoma cells. Immunohistochemical staining of 534 nasopharyngeal carcinomas revealed elevated SPINK6 expression as an independent unfavorable prognostic factor for overall, disease-free, and distant metastasis free survival. Ectopic SPINK6 expression promoted in vitro migration and invasion as well as in vivo lymph node metastasis and liver metastasis of nasopharyngeal carcinoma cells, whereas silencing SPINK6 exhibited opposing effects. SPINK6 enhanced epithelial-mesenchymal transition by activating EGFR and the downstream AKT pathway. Inhibition of EGFR with a neutralizing antibody or erlotinib reversed SPINK6-induced nasopharyngeal carcinoma cell migration and invasion. Erlotinib also inhibited SPINK6-induced metastasis in vivo Notably, SPINK6 bound to the EGFR extracellular domain independent of serine protease-inhibitory activity. Overall, our results identified a novel EGFR-activating mechanism in which SPINK6 has a critical role in promoting nasopharyngeal carcinoma metastasis, with possible implications as a prognostic indicator in nasopharyngeal carcinoma patients. Cancer Res; 77(2); 579-89. (c)2016 AACR. PMID- 27671679 TI - ZIC5 Drives Melanoma Aggressiveness by PDGFD-Mediated Activation of FAK and STAT3. AB - Insights into mechanisms of drug resistance could extend the efficacy of cancer therapy. To probe mechanisms in melanoma, we performed siRNA screening of genes that mediate the development of neural crest cells, from which melanocytes are derived. Here, we report the identification of ZIC5 as a mediator of melanoma drug resistance. ZIC5 is a transcriptional suppressor of E-cadherin expressed highly in human melanoma. ZIC5 enhanced melanoma cell proliferation, survival, drug resistance, in vivo growth and metastasis. Microarray analysis revealed that ZIC5 downstream signaling included PDGFD and FAK activation, which contributes to drug resistance by enhancing STAT3 activation. Silencing of ZIC5 or PDGFD enhanced the apoptotic effects of BRAF inhibition and blocked survival of melanoma cells resistant to BRAF inhibitors. Furthermore, inhibition of FAK or STAT3 suppressed expression of ZIC5, which was positively regulated by PDGFD, FAK, and STAT3 in a positive feedback loop. Taken together, our results identify ZIC5 and PDGFD as candidate therapeutic targets to overcome drug resistance in melanoma. Cancer Res; 77(2); 366-77. (c)2016 AACR. PMID- 27671678 TI - Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes. AB - Using a three-dimensional coculture model, we identified significant subtype specific changes in gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAF). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that fibroblasts strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold. Fibroblasts from normal breast tissues and stromal cultures of brain metastases of breast cancer had similar effects as CAFs. Using synthetic lethality approaches, we identified molecular pathways whose inhibition sensitizes HER2+ breast cancer cells to lapatinib both in vitro and in vivo, including JAK2/STAT3 and hyaluronic acid. Neoadjuvant lapatinib therapy in HER2+ breast tumors lead to a significant increase of phospho-STAT3+ cancer cells and a decrease in the spatial proximity of proliferating (Ki67+) cells to CAFs impacting therapeutic responses. Our studies identify CAF-induced physiologically and clinically relevant changes in cancer cells and offer novel approaches for overcoming microenvironment-mediated therapeutic resistance. Cancer Res; 76(22); 6495-506. (c)2016 AACR. PMID- 27671680 TI - PP2A Inhibitor PME-1 Drives Kinase Inhibitor Resistance in Glioma Cells. AB - Glioblastoma multiforme lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in glioblastoma multiforme, glioma cells exhibit intrinsic resistance toward many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here, we show that overexpression of the protein phosphatase 2A (PP2A) inhibitor protein PME-1 drives resistance of glioma cells to various multikinase inhibitors. The PME-1 elicited resistance was dependent on specific PP2A complexes and was mediated by a decrease in cytoplasmic HDAC4 activity. Importantly, both PME-1 and HDAC4 associated with human glioma progression, supporting clinical relevance of the identified mechanism. Synthetic lethality induced by both PME-1 and HDAC4 inhibition was dependent on the coexpression of proapoptotic protein BAD. Thus, PME-1-mediated PP2A inhibition is a novel mechanistic explanation for multikinase inhibitor resistance in glioma cells. Clinically, these results may inform patient stratification strategies for future clinical trials with selected kinase inhibitors in glioblastoma multiforme. Cancer Res; 76(23); 7001-11. (c)2016 AACR. PMID- 27671682 TI - Rebuttal - Factors affecting cognitive performance in children with special reference to sleep and sedentary behavior. PMID- 27671681 TI - Medications influencing central cholinergic neurotransmission affect saccadic and smooth pursuit eye movements in healthy young adults. AB - RATIONALE: Acetylcholine is an important neuromodulator in the central nervous system, where it plays a significant role in central functions such as the regulation of movement. OBJECTIVE: This study investigated the pharmacological effects of over-the-counter anticholinergic medications on saccadic and smooth pursuit eye movements, in order to establish the significance of central cholinergic pathways in the control of these centrally regulated oculomotor processes. METHODS: Sixteen subjects (mean age 23 +/- 3 years, 9 females) performed pro-saccadic, anti-saccadic and smooth pursuit eye movement tests, while an eye tracker collected eye movement data. Oculomotor assessments were performed pre-ingestion, 0.5 and 2 h post-ingestion of drugs with varying degrees of central anticholinergic properties. The drugs tested were promethazine, hyoscine hydrobromide, hyoscine butylbromide and placebo. RESULTS: The drug intervention with stronger central anticholinergic properties, promethazine, decreased amplitude and increased velocity in the pro-saccadic task and increased duration in the anti-saccadic task. Promethazine, once again, was the only drug to decrease eye velocity in the smooth pursuit test. CONCLUSION: The prominent effects of the stronger central anticholinergic promethazine, on saccadic and smooth pursuit eye movements, potentially conveys the significance of central cholinergic pathways in the control of these centrally regulated oculomotor processes. PMID- 27671684 TI - Durable treatment of ameloblastoma with single agent BRAFi Re: Clinical and radiographic response with combined BRAF-targeted therapy in stage 4 ameloblastoma. PMID- 27671683 TI - Programmable Potentials: Approximate N-body potentials from coarse-level logic. AB - This paper gives a systematic method for constructing an N-body potential, approximating the true potential, that accurately captures meso-scale behavior of the chemical or biological system using pairwise potentials coming from experimental data or ab initio methods. The meso-scale behavior is translated into logic rules for the dynamics. Each pairwise potential has an associated logic function that is constructed using the logic rules, a class of elementary logic functions, and AND, OR, and NOT gates. The effect of each logic function is to turn its associated potential on and off. The N-body potential is constructed as linear combination of the pairwise potentials, where the "coefficients" of the potentials are smoothed versions of the associated logic functions. These potentials allow a potentially low-dimensional description of complex processes while still accurately capturing the relevant physics at the meso-scale. We present the proposed formalism to construct coarse-grained potential models for three examples: an inhibitor molecular system, bond breaking in chemical reactions, and DNA transcription from biology. The method can potentially be used in reverse for design of molecular processes by specifying properties of molecules that can carry them out. PMID- 27671685 TI - Response. PMID- 27671686 TI - Diagnosis and prevalence of Theileria equi horses in western Mexico by nested PCR. AB - Theileria equi infection prevalence was calculated from 1000 blood samples obtained from apparently healthy horses in western Mexico. Samples were sent to the Animal Biotechnology Laboratory of the University of Guadalajara (Mexico) for T. equi diagnosis. Nested polymerase chain reaction (nPCR) was used as a diagnostic method to detect pathogen DNA. Using primers for the merozoite antigen 1 (EMA-1) gene, 19.70+/-2.47% of the horses (95% CI, 17.23-22.17%) tested positive for T. equi. There was no significant association between gender and T. equi infection. However, prevalence was higher among stabled horses (25.81%) than that among grazing horses (15.02%). The positivity rate was also higher among Quarter Horse (24.70%), Lusitano (35.90%), and Costa Rican Saddle Horse (47.37%) breeds than that among the other seven breeds investigated in this study. The percentage of T. equi infection was higher among adult horses (>= 4years old, 25.05%) than that among colts and fillies (2-4years old, 15.48%), yearlings (1 2years old, 10.49%), and foals (<1year old, 10.34%). This is the first study of T. equi infection prevalence among horses in Mexico by nPCR . The results indicate that the equine piroplasmosis (EP) caused by T. equi is enzootic in western Mexico. PMID- 27671688 TI - SACN is committed to openness and engagement. PMID- 27671687 TI - Oxymatrine synergistically enhances antitumor activity of oxaliplatin in colon carcinoma through PI3K/AKT/mTOR pathway. AB - Oxymatrine (OMT), one of the main active components of extracts from the dry roots of Sophora flavescens, has been reported to possess many pharmacological properties including cancer-preventive and anti-cancer effects. The aim of the present study is to explore the efficiency of combination therapy with OMT and oxaliplatin (OXA) and identify the in vitro and in vivo cytotoxicity on colon cancer lines (HT29 and SW480) and mice model. Cells were treated with OMT and/or OXA and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay and immunohistochemistry. The results demonstrated that OMT and OXA inhibited the proliferation of colon cancer cells, and combination therapy of OMT and OXA resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with OMT and OXA caused G0/G1 phase arrest by upregulating P21, P27 and downregulating cyclin D, and induced apoptosis through decreasing the expression of p-PI3K, p-AKT, p-mTOR, p-p70S6K. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly neutralized the pro-apoptotic activity of OXA + OMT, demonstrating the important role of PI3K/AKT in this process. Moreover, in nude mice model, co treatment displayed more efficient inhibition of tumor weight and volume on SW480 xenograft mouse model than single-agent treatment with OXA or OMT. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation, which consistent with our in vitro results. In conclusion, our findings highlight that the combination therapy with OMT and OXA exerted synergistic antitumor effects in colon cancer cells through PI3K/AKT/mTOR pathway and combination treatment with OMT and OXA would be a promising therapeutic strategy for colon carcinoma treatment. PMID- 27671689 TI - Taxes on Sugar-Sweetened Beverages: A Strategy to Reduce Epidemics of Diabetes, Obesity, and Dental Caries? PMID- 27671691 TI - ? PMID- 27671690 TI - Effects of Taxing Sugar-Sweetened Beverages on Caries and Treatment Costs. AB - Caries increment is affected by sugar-sweetened beverage (SSB) consumption. Taxing SSBs could reduce sugar consumption and caries increment. The authors aimed to estimate the impact of a 20% SSB sales tax on caries increment and associated treatment costs (as well as the resulting tax revenue) in the context of Germany. A model-based approach was taken, estimating the effects for the German population aged 14 to 79 y over a 10-y period. Taxation was assumed to affect beverage-associated sugar consumption via empirical demand elasticities. Altered consumption affected caries increments and treatment costs, with cost estimates being calculated under the perspective of the statutory health insurance. National representative consumption and price data were used to estimate tax revenue. Microsimulations were performed to estimate health outcomes, costs, and revenue impact in different age, sex, and income groups. Implementing a 20% SSB sales tax reduced sugar consumption in nearly all male groups but in fewer female groups. The reduction was larger among younger than older individuals and among those with low income. Taxation reduced caries increment and treatment costs especially in younger (rather than older) individuals and those with low income. Over 10 y, mean (SD) net caries increments at the population level were 82.27 (1.15) million and 83.02 (1.08) million teeth at 20% and 0% SSB tax, respectively. These generated treatment costs of 2.64 (0.39) billion and 2.72 (0.35) billion euro, respectively. Additional tax revenue was 37.99 (3.41) billion euro over the 10 y. In conclusion and within the limitations of this study's perspective, database, and underlying assumptions, implementing a 20% sales tax on SSBs is likely to reduce caries increment, especially in young low-income males, thereby also reducing inequalities in the distribution of caries experience. Taxation would also reduce treatment costs. However, these reductions might be limited in the total population. PMID- 27671692 TI - [Peter Brunner : 20.09.1932 - 14.04.2016]. PMID- 27671693 TI - Finding the balance between over- and under-treatment of ductal carcinoma in situ (DCIS). AB - With the widespread adoption of population-based breast cancer screening, ductal carcinoma in situ (DCIS) has come to represent 20-25% of all breast neoplastic lesions diagnosed. Current treatment aims at preventing invasive breast cancer, but the majority of DCIS lesions will never progress to invasive disease. Still, DCIS is treated by surgical excision, followed by radiotherapy as part of breast conserving treatment, and/or endocrine therapy. This implies over-treatment of the majority of DCIS, as less than 1% of DCIS patients will go on to develop invasive breast cancer annually. If we are able to identify which DCIS is likely to progress or recur as invasive breast cancer and which DCIS would remain indolent, we can treat the first group intensively, while sparing the second group from such unnecessary treatment (surgery, radiotherapy, endocrine therapy) preserving the quality of life of these women. This review summarizes our current knowledge on DCIS and the risks involved regarding progression into invasive breast cancer. It also shows current knowledge gaps, areas where profound research is highly necessary for women with DCIS to prevent their over-treatment in case of a harmless DCIS, but provide optimal treatment for potentially hazardous DCIS. PMID- 27671694 TI - Relationship between renal function and circulating microparticles, soluble P selectin and E-selectin levels in atrial fibrillation. AB - Atrial fibrillation (AF) and chronic kidney disease are closely related, and any associated risk of stroke and thromboembolism due to AF is increased by concurrent renal dysfunction. The mechanism(s) for this include abnormalities in platelets and endothelial cells. We hypothesized relationships between levels of circulating platelet microparticles (PMPs, defined by CD42b), soluble P selectin (both reflecting platelet activation), soluble E-selectin (reflecting endothelial activation) and endothelial/platelet microparticles (EPMPs, defined by CD31) with progressive renal dysfunction. Blood samples were obtained from 160 anticoagulated AF patients. Microparticles were measured by flow cytometry, soluble E and P selectin levels by ELISA. Renal function was determined by estimated glomerular filtration rate (eGFR). EPMP levels demonstrated a linear increased trend across quartiles of eGFR (p = 0.034) and CKD stage (p < 0.001), and correlated with eGFR and serum creatinine (p < 0.01). PMPs, P-selectin and E selectin levels were not significantly different across groupings of renal dysfunction, and no significant correlations with eGFR were evident (p = 0.186, p = 0.561, p = 0.746 respectively). Stepwise multivariable regression analysis demonstrated that worsening renal function was an independent predictor of EPMP levels (p < 0.001). In well-anticoagulated AF patients, there is potential relationship between endothelial function (as judged by elevated EPMP levels, with no change in PMPs) and renal function. Other markers of prothombotic state or cellular activation (PMP, P-selectin and E-selectin levels) were not significantly different across the various degree of renal dysfunction. Renal function must be addressed when measuring EPMP levels. PMID- 27671695 TI - Improved racemate resolution of pentan-2-ol and trans-(Z)-cyclooct-5-ene-1,2-diol by lipase catalysis. AB - Lipases are important catalysts in chiral synthesis due to their wide substrate recognition combined with a high stereoselectivity. We demonstrate here that the state, free or immobilized, of Candida antarctica lipase B (CaLB) affects enantioselectivity and also alters the temperature dependancy of the enzyme. This indicates that CaLB undergoes various conformations induced by its interaction with the different immobilization supports studied. Molecular imprinting experiments, using immobilized enzyme co-dried with mimic substrate molecules, enhanced the enantiomeric ratio two-fold or three-fold, depending on the immobilization support. The structure of the acyl donor has a pronounced effect on CaLB catalyzed resolution, due to the proximity of the acyl and alcohol moieties during catalysis. When the acylation of pentan-2-ol was examined, we found that the 3C methyl propanoate donor afforded the highest resolution. Trans (Z)-cyclooct-5-en-1,2-diol was used as a model racemic substrate to study the ability of lipase to catalyze the resolution of difunctionalized compounds. There was a clear enhancement in the enantiomer selectivity of the biotransformation of the diol when vinyl butanoate is used as the acyl donor. The conversion and enantiomeric excess of (1R,2R)-monoacetates were enhanced, using immobilized CaLB, when the chain length of the donors increased from C2 to C4. PMID- 27671696 TI - Complete genome sequence of Lactobacillus plantarum LZ206, a potential probiotic strain with antimicrobial activity against food-borne pathogenic microorganisms. AB - Lactobacilli strains have been considered as important candidates for manufacturing "natural food", due to their antimicrobial properties and generally regarded as safe (GRAS) status. Lactobacillus plantarum LZ206 is a potential probiotic strain isolated from raw cow milk, with antimicrobial activity against various pathogens, including Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes), Gram-negtive bacteria (Escherichia coli and Salmonella enterica), and fungus Candida albicans. To better understand molecular base for its antimicrobial activity, entire genome of LZ206 was sequenced. It was revealed that genome of LZ206 contained a circular 3,212,951-bp chromosome, two circular plasmids and one predicted linear plasmid. A plantaricin gene cluster, which is responsible for bacteriocins biosynthesis and could be associated with its broad spectrum antimicrobial activity, was identified based on comparative genomic analysis. Whole genome sequencing of L. plantarum LZ206 might facilitate its applications to protect food products from pathogens' contamination in the dairy industry. PMID- 27671697 TI - Complete genome sequence of Bacillus amyloliquefaciens subsp. plantarum S499, a rhizobacterium that triggers plant defences and inhibits fungal phytopathogens. AB - Bacillus amyloliquefaciens subsp. plantarum S499 is a plant beneficial rhizobacterium with a good antagonistic potential against phytopathogens through the release of active secondary metabolites. Moreover, it can induce systemic resistance in plants by producing considerable amounts of surfactins. The complete genome sequence of B. amyloliquefaciens subsp. plantarum S499 includes a circular chromosome of 3,927,922bp and a plasmid of 8,008bp. A remarkable abundance in genomic regions of putative horizontal origin emerged from the analysis. Furthermore, we highlighted the presence of genes involved in the establishment of interactions with the host plants at the root level and in the competition with other soil-borne microorganisms. More specifically, genes related to the synthesis of amylolysin, amylocyclicin, and butirosin were identified. These antimicrobials were not known before to be part of the antibiotic arsenal of the strain. The information embedded in the genome will support the upcoming studies regarding the application of B. amyloliquefaciens isolates as plant-growth promoters and biocontrol agents. PMID- 27671698 TI - Circular RNAs are miRNA sponges and can be used as a new class of biomarker. AB - Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that are involved in transcriptional and posttranscriptional gene expression regulation. The development of deep sequencing of ribosomal RNA (rRNA)-depleted RNA libraries, associated with improved computational tools, has provided the identification of several new circRNAs in all sorts of organisms, from protists, plants and fungi to animals. Recently, it was discovered that endogenous circRNAs can work as microRNA (miRNA) sponges. This means that the circRNAs bind to miRNAs and consequently repress their function, providing a new model of action for this class of ncRNA, as well as indicating another mechanism that regulates miRNA activity. As miRNAs control a large set of biological processes, circRNA sponge activity will also affect these pathways. Several studies have associated miRNA sponges with human diseases, including osteoarthritis, diabetes, neurodegenerative pathologies and several types of cancer. Additionally, high stability, abundance and tissue-specific expression patterns make circRNA sponges very attractive for clinical research. Herein, we review the biogenesis, properties and function of endogenous circRNA sponges, with a special focus on those related to human cancer. A list of web tools available for the study of circRNAs is also given. Additionally, we discuss the possibility of using circRNAs as molecular markers for the diagnosis of diseases. PMID- 27671699 TI - Development of a patient-reported outcome measure for upper limb function in Duchenne muscular dystrophy: DMD Upper Limb PROM. AB - AIM: To develop a patient-reported outcome measure (PROM) assessing upper limb function related to activities of daily living (ADL) that cannot be observed in a clinical setting, specifically for patients with Duchenne muscular dystrophy (DMD) across a wide age range, applicable in the different stages of the disease. METHOD: The developmental process was based on US Food and Drug Administration guidelines. This included item generation from a systematic review of existing tools and expert opinion on task difficulty and relevance, involving individuals with DMD. Cultural aspects affecting ADL were taken into consideration to make this tool applicable to the broad DMD community. Items were selected in relation to a conceptual framework reflecting disease progression covering the full range of upper limb function across different ADL domains. RESULTS: After pilot testing and iterative Rasch analyses, redundant or clinically irrelevant items were removed. The final questionnaire consists of 32 items covering four domains of ADL (food, self-care, household and environment, leisure and communication). Test retest reliability was excellent. INTERPRETATION: A DMD-specific upper limb PROM was developed on the basis of clinical relevance and psychometric robustness. Its main purpose is to document the patient self-reported natural history of DMD and assess the efficacy of interventions. PMID- 27671700 TI - Communication, Leadership, and Decision-Making in the Neuro-ICU. AB - The Neuro-ICU is a multidisciplinary location that presents peculiar challenges and opportunities for patients with life-threatening neurological disease. Communication skills are essential in supporting caregivers and other embedded providers (e.g., neurosurgeons, advanced practice providers, nurses, pharmacists), through leadership. Limitations to prognostication complicate how decisions are made on behalf of non-communicative patients. Cognitive dysfunction and durable reductions in health-related quality of life are difficult to predict, and the diagnosis of brain death may be challenging and confounded by medications and comorbidities. The Neuro-ICU team, as well as utilization of additional consultants, can be structured to optimize care. Future research should explore how to further improve the composition, communication and interactions of the Neuro-ICU team to maximize outcomes, minimize caregiver burden, and promote collegiality. PMID- 27671703 TI - Clinical implications of hepatobiliary scintigraphy and ultrasound in the diagnosis of acute cholecystitis. AB - BACKGROUND: We assess the performance of ultrasound (US) and hepatobiliary scintigraphy (HIDA) as confirmatory studies in acute cholecystitis (AC) and demonstrate our current imaging protocol's impact on outcomes. STUDY DESIGN: Between January 2013 to July 2014, 117 patients were admitted through the emergency room with a preliminary diagnosis of AC. Overall, 106/117 (91%) of the patients received US preadmission and 34/117 (29%) received a HIDA post admission. Primary end points included: 1) diagnostic test reliability for AC, and 2) outcome and quality measures (time to surgery, LOS, costs, etc.). RESULTS: Laparoscopic cholecystectomy was performed in 96/117 (82%) and open cholecystectomy in 21/117 (18%) of the patients. Overall, histopathologic features consistent with AC was present in 46/117 (39%). AC alone was present in 23/117 (20%), and AC superimposed on chronic cholecystitis was present in 23/117 (20%). For AC, US had a sensitivity and specificity of 26% and 80%, respectively. HIDA scan had a sensitivity and specificity of 87% and 79%, respectively. Time to surgery (TTS) was 4 vs 2.3 days in patients who received HIDA vs US alone (p = 0.001), and length of stay (LOS) was 6.7 vs 4.3 days, respectively (p = 0.001). Age >50 years, glucose >140 (mg/dl), and WBC count >10 (*109 /L) were statistically significant independent variables associated with AC. CONCLUSION: HIDA scan is superior to US as a diagnostic study in the setting of AC. Our current protocol of delayed HIDA (post-admission) was associated with increased TTS, LOS, and overall costs. Early confirmation with HIDA in high risk patients may hasten treatment allocation and improve outcomes in the setting of AC. PMID- 27671701 TI - Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption. AB - Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D3, and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring. PMID- 27671704 TI - Direct and indirect costs for anal fistula in Sweden. AB - INTRODUCTION: Anal fistula is an abnormal tract with an external and internal opening that cause leakage, discomfort, and occasionally pain. Surgery is standard treatment, but recurrence and anal incontinence is common. The objective of the study was to analyze resource use, costs and sick leave for newly diagnosed patients with anal fistula in Sweden. METHODS: The study was based on register data from linkages between Swedish population-based registers including patients treated for anal fistula in Vastra Gotaland County, Sweden. Health care resource use, costs and sick leave were estimated. RESULTS: The sample included 362 patients of which 27% had no surgery, 37% had one surgery and 36% had multiple surgeries. Patients with multiple surgeries underwent over four surgeries on average. Approximately 67% of the contacts occurred during the first year after diagnosis. Estimated mean sick leave was 10.4 full-time equivalent days per patient. Total discounted costs were ?5,561 per patient where approximately 80% were direct costs. DISCUSSION: To our knowledge this is the first study of resource use, costs and sick leave related to anal fistulas. The study indicates that anal fistula is a condition that is costly for society and that the burden of anal fistula in terms of health care resources and sick leave is especially high for patients experiencing multiple surgeries. CONCLUSION: Anal fistula is a condition that is costly for society and there is an unmet need for the group of patients with multiple surgeries to find appropriate treatment interventions. PMID- 27671706 TI - T1-weighted basal ganglia hyperintensities due to gadolinium deposition - a cautionary note. PMID- 27671707 TI - Strength and performance asymmetry during maximal velocity sprint running. AB - The aim of this study was to empirically examine the interaction of athlete specific kinematic kinetic and strength asymmetry in sprint running. Bilateral ground reaction force and kinematic data were collected during maximal velocity (mean = 9.05 m/s) sprinting for eight athletes. Bilateral ground reaction force data were also collected while the same athletes performed maximal effort squat jumps. Using novel composite asymmetry scores, interactions between kinematic and kinetic asymmetry were compared for the group of sprinters. Asymmetry was greater for kinematic variables than step characteristics, with largest respective values of 6.68% and 1.68%. Kinetic variables contained the largest asymmetry values, peaking at >90%. Asymmetry was present in all kinematic and kinetic variables analyzed during sprint trials. However, individual athlete asymmetry profiles were reported for sprint and jump trials. Athletes' sprint performance was not related to their overall asymmetry. Positive relationships were found between asymmetry in ankle work during sprint running and peak vertical force (r = 0.895) and power (r = 0.761) during jump trials, suggesting that the ankle joint may be key in regulating asymmetry in sprinting and highlighting the individual nature of asymmetry. The individual athlete asymmetry profiles and lack of relationship between asymmetry of limb strength and sprint performance suggest that athletes are not "limb dominant" and that strength imbalances are joint and task specific. Compensatory kinetic mechanisms may serve to reduce the effects of strength or biological asymmetry on the performance outcome of step velocity. PMID- 27671705 TI - Longitudinal Associations between Depression and Aggression in Children and Adolescents. AB - Due to the longstanding and detrimental effects of engaging in aggressive behaviour and of experiencing symptoms of internalizing problems in children and adolescents, there is an increasing interest in identifying the temporal sequence between these 2 problems with previous research yielding inconsistent findings. Therefore, the longitudinal links between relational aggression, physical aggression, and depression were examined across 7 years in a sample of 643 children (54 % girls) aged 10 at Time 1. Three models were compared- (1) the failure model, in which aggression predicted depression, (2) the acting out model, in which depression predicted aggression, and (3) a reciprocal model, in which both aggression and depression shared a reciprocal relation over time. Cross-lagged path analyses using structural equation modeling supported the failure model (i.e., engaging in relational and physical aggression predicts subsequent depressive symptoms). Findings were similar for boys and girls. These findings add to the literature suggesting that externalizing problems precede internalizing problems. PMID- 27671708 TI - Neurophysiological correlates of abnormal somatosensory temporal discrimination in dystonia. AB - BACKGROUND: Somatosensory temporal discrimination threshold is often prolonged in patients with dystonia. Previous evidence suggested that this might be caused by impaired somatosensory processing in the time domain. Here, we tested if other markers of reduced inhibition in the somatosensory system might also contribute to abnormal somatosensory temporal discrimination in dystonia. METHODS: Somatosensory temporal discrimination threshold was measured in 19 patients with isolated cervical dystonia and 19 age-matched healthy controls. We evaluated temporal somatosensory inhibition using paired-pulse somatosensory evoked potentials, spatial somatosensory inhibition by measuring the somatosensory evoked potentials interaction between simultaneous stimulation of the digital nerves in thumb and index finger, and Gamma-aminobutyric acid-ergic (GABAergic) sensory inhibition using the early and late components of high-frequency oscillations in digital nerves somatosensory evoked potentials. RESULTS: When compared with healthy controls, dystonic patients had longer somatosensory temporal discrimination thresholds, reduced suppression of cortical and subcortical paired-pulse somatosensory evoked potentials, less spatial inhibition of simultaneous somatosensory evoked potentials, and a smaller area of the early component of the high-frequency oscillations. A logistic regression analysis found that paired pulse suppression of the N20 component at an interstimulus interval of 5 milliseconds and the late component of the high-frequency oscillations were independently related to somatosensory temporal discrimination thresholds. "Dystonia group" was also a predictor of enhanced somatosensory temporal discrimination threshold, indicating a dystonia-specific effect that independently influences this threshold. CONCLUSIONS: Increased somatosensory temporal discrimination threshold in dystonia is related to reduced activity of inhibitory circuits within the primary somatosensory cortex. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27671709 TI - Inverted Silicon Nanopencil Array Solar Cells with Enhanced Contact Structures. AB - Although three-dimensional nanostructured solar cells have attracted extensive research attention due to their superior broadband and omnidirectional light harvesting properties, majority of them are still suffered from complicated fabrication processes as well as disappointed photovoltaic performances. Here, we employed our newly-developed, low-cost and simple wet anisotropic etching to fabricate hierarchical silicon nanostructured arrays with different solar cell contact design, followed by systematic investigations of their photovoltaic characteristics. Specifically, nano-arrays with the tapered tips (e.g. inverted nanopencils) are found to enable the more conformal top electrode deposition directly onto the nanostructures for better series and shunt conductance, but its insufficient film coverage at the basal plane would still restrict the charge carrier collection. In contrast, the low-platform contact design facilitates a substantial photovoltaic device performance enhancement of ~24%, as compared to the one of conventional top electrode design, due to the shortened current path and improved lateral conductance for the minimized carrier recombination and series resistance. This enhanced contact structure can not only maintain excellent photon-trapping behaviors of nanostructures, but also help to eliminate adverse impacts of these tapered nano-morphological features on the contact resistance, providing further insight into design consideration in optimizing the contact geometry for high-performance nanostructured photovoltaic devices. PMID- 27671710 TI - Unlocking the black box: teaching mathematical modeling with popular culture. AB - Mathematical modeling is an important tool in biological research, allowing for the synthesis of results from many studies into an understanding of a system. Despite this, the need for extensive subject matter knowledge and complex mathematics often leaves modeling as an esoteric subspecialty. A 2-fold approach can be used to make modeling more approachable for students and those interested in obtaining a functional knowledge of modeling. The first is the use of a popular culture disease system-a zombie epidemic-to allow for exploration of the concepts of modeling using a flexible framework. The second is the use of available interactive and non-calculus-based tools to allow students to work with and implement models to cement their understanding. PMID- 27671711 TI - Degradation of carbonyl sulfide by Actinomycetes and detection of clade D of beta class carbonic anhydrase. AB - Carbonyl sulfide (COS) is an atmospheric trace gas and one of the sources of stratospheric aerosol contributing to climate change. Although one of the major sinks of COS is soil, the distribution of COS degradation ability among bacteria remains unclear. Seventeen out of 20 named bacteria belonging to Actinomycetales had COS degradation activity at mole fractions of 30 parts per million by volume (ppmv) COS. Dietzia maris NBRC 15801T and Mycobacterium sp. THI405 had the activity comparable to a chemolithoautotroph Thiobacillus thioparus THI115 that degrade COS by COS hydrolase for energy production. Among 12 bacteria manifesting rapid degradation at 30 ppmv COS, Dietzia maris NBRC 15801T and Streptomyces ambofaciens NBRC 12836T degraded ambient COS (~500 parts per trillion by volume). Geodermatophilus obscurus NBRC 13315T and Amycolatopsis orientalis NBRC 12806T increased COS concentrations. Moreover, six of eight COS degrading bacteria isolated from soils had partial nucleotide sequences similar to that of the gene encoding clade D of beta-class carbonic anhydrase, which included COS hydrolase. These results indicate the potential importance of Actinomycetes in the role of soils as sinks of atmospheric COS. PMID- 27671712 TI - The role of subchondral bone damage in post-traumatic osteoarthritis. AB - Osteoarthritis (OA), the most common musculoskeletal disease in the United States, is characterized by cartilage breakdown, pain, and restricted movement. Post-traumatic OA (PTOA) occurs subsequent to traumatic joint injury, such as anterior cruciate ligament (ACL) rupture, and makes up 12% of the overall disease burden, with healthcare costs of approximately $3 billion/year. The current paradigm for PTOA is based on the observation that joint injury affects multiple tissues, all of which may contribute to subsequent joint failure. Subchondral bone plays a significant role in PTOA, as shown by magnetic resonance imaging evidence that subchondral bone marrow lesions (BMLs) are present in 80% of ACL rupture cases immediately after joint injury. The presence of BMLs indicates an acute consequence of injury, specifically in subchondral bone, which could be targeted with preventative therapy. BMLs may be a direct representation of physical damage to bone tissue. Interestingly, microdamage is known to induce osteoclast-mediated remodeling in bone. Furthermore, the contiguous link between subchondral bone and articular cartilage may allow transport of small molecules, resulting from these remodeling processes, to cross the osteochondral junction and contribute to PTOA development. Targeting subchondral bone by inhibiting subchondral remodeling, particularly in the early phase postinjury, may be a potential approach for preventing PTOA. PMID- 27671713 TI - Investigation on the anaerobic propionate degradation by Escherichia coli K12. AB - Propionate is an abundant carboxylic acid in nature. Microorganisms metabolize propionate aerobically via the 2-methylcitrate pathway. This pathway depends on a series of three reactions in the citric acid cycle that leads to the conversion of succinate to oxaloacetate. Interestingly, the gamma-proteobacterium Escherichia coli can use propionate as a carbon and electron source under oxic but not under anoxic conditions. RT-PCR and transcriptomic analysis revealed a posttranscriptional regulation of the prpBCDE-gene cluster encoding the necessary enzymes for propionate metabolism. The polycistronic mRNA seems to be hydrolyzed in the 3'-5' direction under anoxic conditions. This regulatory strategy is highly constructive because the last gene of the operon encodes the first enzyme of the propionate metabolism. Further analysis revealed that RNase R is involved in the hydrolysis of the prp transcripts. Consequently, an rnr-deletion strain could metabolize propionate under anoxic conditions. To the best of our knowledge, this is the first study describing the influence of RNase R on the anaerobic metabolism of E. coli. PMID- 27671714 TI - Vestibular Neuritis With Minimal Canal Paresis: Characteristics and Clinical Implication. AB - OBJECTIVES: To analyze the clinical characteristics of vestibular neuritis patients with minimal canal paresis (canal paresis <25%). METHODS: Patients clinically diagnosed with vestibular neuritis and treated at our institute (n=201) underwent otoneurological examination and vestibular function tests. Patients were categorized in terms of the results of caloric testing (canal paresis<25%, n=58; canal paresis>=25%, n=143). Clinical characteristics and laboratory outcomes were compared between two groups. RESULTS: Existence of underlying diseases, preceding symptoms, and direction of spontaneous nystagmus were not different between the groups. The mean duration of spontaneous nystagmus was shortest in the minimal canal paresis group (P<0.001) and the direction of spontaneous nystagmus changed more frequently in this group (P<0.001) during recovery. Among the subgroup with minimal canal paresis, only 29.5% had an abnormal finding on the rotatory chair test, as compared to 81.5% of the canal paresis group. The minimal canal paresis group showed higher sensory organization test scores in computerized dynamic posturography. CONCLUSION: Patients with minimal canal paresis (canal paresis <25%) show similar clinical manifestations as conventional vestibular neuritis patients, but have faster recovery of symptoms and a higher incidence of recovery nystagmus. This finding support that the minimal canal paresis could be considered as a milder type of vestibular neuritis. PMID- 27671715 TI - The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application. AB - OBJECTIVES: This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. METHODS: FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. RESULTS: FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (P<0.05). In the clinical trial, significant improvements in the majority of the subjective and objective voice parameters were registered 3 months after FGF injection and were maintained at 12 months. Complications associated with the FGF injections, such as granuloma, were not observed during the follow-up period. CONCLUSION: Based on the animal model and the prospective clinical trial, vocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring. PMID- 27671717 TI - Introduction. AB - Alternative approaches to animal testing are gaining momentum with an increasing number of test methods obtaining international acceptance, thanks in large part to the validation efforts conducted on these assays. The principles and process of validation were first established in the 1990s in Europe and USA, and further gained international recognition ensuring the broader acceptance of alternative test methods at a regulatory level. If these principles were successful in pioneering the regulatory acceptance of alternative methods for less complex endpoints, an evolution of concepts is needed to embrace emerging technologies and the increased complexity of endpoints. Innovative concepts and approaches of scientific validation can help to ensure the continued regulatory and international acceptance of novel alternative methods and technologies for toxicity testing such as human-based in vitro models derived from induced pluripotent stem cells and significant advances in bioengineering. This chapter provides a historical overview of the establishment and evolution of the principles of the scientific validation of alternative methods for toxicity testing as well as the challenges and opportunities for adapting those principles to keep pace with scientific progress whilst ensuring human safety and best serve the needs of society. PMID- 27671716 TI - Analysis of Prognostic Factors in Malignant External Otitis. AB - OBJECTIVES: Malignant external otitis (MEO) is a potentially fatal infection of the external auditory canal, temporal bone, and skull base. Despite treatment with modern antibiotics, MEO can lead to skull base osteomyelitis. Until now, there have been few studies on the prognostic factors of MEO. METHODS: We performed a retrospective study to identify prognostic factors of MEO, and a meta analysis of other articles investigating MEO. On the basis of disease progression the 28 patients in our study were divided into 'controlled' and 'uncontrolled' groups, consisting of 12 and 16 patients, respectively. We identified three categories of prognostic factors: those related to patient, disease, and treatment. We compared these prognostic factors between the controlled and uncontrolled groups. RESULTS: In our study, the duration of diabetes mellitus (DM), presence of inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), and computed tomography or magnetic resonance imaging findings influenced the prognosis of MEO. In contrast, prognosis was unrelated to age, gender, mean glucose level, hemoglobin A1c level, pathogen, comorbidity, or cranial nerve involvement. No factor related to treatment modality was correlated with prognosis, such as surgery, steroid therapy, or interval to the first appropriate treatment. Cranial nerve involvement has been proven to be associated with disease progression, but the relationship between cranial nerve involvement and the prognosis of MEO remains controversial. As a part of this study, we conducted a meta-analysis of cranial nerve involvement as a prognostic factor of MEO. We found that cranial nerve involvement has a statistically significant influence on the prognosis of MEO. CONCLUSION: We found that glycemic control in diabetes mellitus, cranial nerve involvement, and the extent of disease determined from various imaging modalities influence the prognosis of MEO. We suggest that significant prognostic factors should be monitored to determine the prognosis of patients with MEO. PMID- 27671718 TI - Validation in Support of Internationally Harmonised OECD Test Guidelines for Assessing the Safety of Chemicals. AB - Ten years elapsed since the OECD published the Guidance document on the validation and international regulatory acceptance of test methods for hazard assessment. Much experience has been gained since then in validation centres, in countries and at the OECD on a variety of test methods that were subjected to validation studies. This chapter reviews validation principles and highlights common features that appear to be important for further regulatory acceptance across studies. Existing OECD-agreed validation principles will most likely generally remain relevant and applicable to address challenges associated with the validation of future test methods. Some adaptations may be needed to take into account the level of technique introduced in test systems, but demonstration of relevance and reliability will continue to play a central role as pre requisite for the regulatory acceptance. Demonstration of relevance will become more challenging for test methods that form part of a set of predictive tools and methods, and that do not stand alone. OECD is keen on ensuring that while these concepts evolve, countries can continue to rely on valid methods and harmonised approaches for an efficient testing and assessment of chemicals. PMID- 27671719 TI - Regulatory Acceptance of Alternative Methods in the Development and Approval of Pharmaceuticals. AB - Animal studies may be carried out to support first administration of a new medicinal product to either humans or the target animal species, or before performing clinical trials in even larger populations, or before marketing authorisation, or to control quality during production. Ethical and animal welfare considerations require that animal use is limited as much as possible. Directive 2010/63/EU on the protection of animals used for scientific purposes unambiguously fosters the application of the principle of the 3Rs when considering the choice of methods to be used.As such, today, the 3Rs are embedded in the relevant regulatory guidance both at the European (European Medicines Agency (EMA)) and (Veterinary) International Conference on Harmonization ((V)ICH) levels. With respect to non-clinical testing requirements for human medicinal products, reduction and replacement of animal testing has been achieved by the regulatory acceptance of new in vitro methods, either as pivotal, supportive or exploratory mechanistic studies. Whilst replacement of animal studies remains the ultimate goal, approaches aimed at reducing or refining animal studies have also been routinely implemented in regulatory guidelines, where applicable. The chapter provides an overview of the implementation of 3Rs in the drafting of non clinical testing guidelines for human medicinal products at the level of the ICH. In addition, the revision of the ICH S2 guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use is discussed as a case study.In October 2010, the EMA established a Joint ad hoc Expert Group (JEG 3Rs) with the mandate to improve and foster the application of 3Rs principles to the regulatory testing of medicinal products throughout their lifecycle. As such, a Guideline on regulatory acceptance of 3R testing approaches was drafted that defines regulatory acceptance and provides guidance on the scientific and technical criteria for regulatory acceptance of 3R testing approaches, including a process for collection of real-life data (safe harbour). Pathways for regulatory acceptance of 3R testing approaches are depicted and a new procedure for submission and evaluation of a proposal for regulatory acceptance of 3R testing approaches is described. PMID- 27671720 TI - Validation of Alternative In Vitro Methods to Animal Testing: Concepts, Challenges, Processes and Tools. AB - This chapter explores the concepts, processes, tools and challenges relating to the validation of alternative methods for toxicity and safety testing. In general terms, validation is the process of assessing the appropriateness and usefulness of a tool for its intended purpose. Validation is routinely used in various contexts in science, technology, the manufacturing and services sectors. It serves to assess the fitness-for-purpose of devices, systems, software up to entire methodologies. In the area of toxicity testing, validation plays an indispensable role: "alternative approaches" are increasingly replacing animal models as predictive tools and it needs to be demonstrated that these novel methods are fit for purpose. Alternative approaches include in vitro test methods, non-testing approaches such as predictive computer models up to entire testing and assessment strategies composed of method suites, data sources and decision-aiding tools. Data generated with alternative approaches are ultimately used for decision-making on public health and the protection of the environment. It is therefore essential that the underlying methods and methodologies are thoroughly characterised, assessed and transparently documented through validation studies involving impartial actors. Importantly, validation serves as a filter to ensure that only test methods able to produce data that help to address legislative requirements (e.g. EU's REACH legislation) are accepted as official testing tools and, owing to the globalisation of markets, recognised on international level (e.g. through inclusion in OECD test guidelines). Since validation creates a credible and transparent evidence base on test methods, it provides a quality stamp, supporting companies developing and marketing alternative methods and creating considerable business opportunities. Validation of alternative methods is conducted through scientific studies assessing two key hypotheses, reliability and relevance of the test method for a given purpose. Relevance encapsulates the scientific basis of the test method, its capacity to predict adverse effects in the "target system" (i.e. human health or the environment) as well as its applicability for the intended purpose. In this chapter we focus on the validation of non-animal in vitro alternative testing methods and review the concepts, challenges, processes and tools fundamental to the validation of in vitro methods intended for hazard testing of chemicals. We explore major challenges and peculiarities of validation in this area. Based on the notion that validation per se is a scientific endeavour that needs to adhere to key scientific principles, namely objectivity and appropriate choice of methodology, we examine basic aspects of study design and management, and provide illustrations of statistical approaches to describe predictive performance of validated test methods as well as their reliability. PMID- 27671722 TI - Validation of Computational Methods. AB - In this chapter, we provide an overview of how (Quantitative) Structure Activity Relationships, (Q)SARs, are validated and applied for regulatory purposes. We outline how chemical categories are derived to facilitate endpoint specific read across using tools such as the OECD QSAR Toolbox and discuss some of the current difficulties in addressing the residual uncertainties of read-across. Finally we put forward a perspective of how non-testing approaches may evolve in light of the advances in new and emerging technologies and how these fit within the Adverse Outcome Pathway (AOP) framework. PMID- 27671721 TI - Practical Aspects of Designing and Conducting Validation Studies Involving Multi study Trials. AB - This chapter focuses on practical aspects of conducting prospective in vitro validation studies, and in particular, by laboratories that are members of the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) that is coordinated by the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). Prospective validation studies involving EU NETVAL, comprising a multi-study trial involving several laboratories or "test facilities", typically consist of two main steps: (1) the design of the validation study by EURL ECVAM and (2) the execution of the multi-study trial by a number of qualified laboratories within EU-NETVAL, coordinated and supported by EURL ECVAM. The approach adopted in the conduct of these validation studies adheres to the principles described in the OECD Guidance Document on the Validation and International Acceptance of new or updated test methods for Hazard Assessment No. 34 (OECD 2005). The context and scope of conducting prospective in vitro validation studies is dealt with in Chap. 4 . Here we focus mainly on the processes followed to carry out a prospective validation of in vitro methods involving different laboratories with the ultimate aim of generating a dataset that can support a decision in relation to the possible development of an international test guideline (e.g. by the OECD) or the establishment of performance standards. PMID- 27671723 TI - Implementation of New Test Methods into Practical Testing. AB - New toxicology test methods, especially those using in vitro methods, are continually being developed. Some are used by industry for screening purposes; others are eventually validated for regulatory use. However, for a new test method to be firmly adopted by industry it must be readily available, generally through an in-house industry laboratory, an academic laboratory, or a contract research organization. Regardless of the type of laboratory which intends to implement the test method, certain steps must be taken to ascertain that the method that is put into place is reproducible and performs identically to the test method that was published or has undergone validation. This involves developing protocols and standard operating procedures, training staff, developing historic positive and negative control data, establishing acceptable performance with proficiency chemicals, and addressing all the safety concerns that may accompany the assay. From experience within a contract research laboratory, we provide guidance on how to most efficiently accomplish these tasks. PMID- 27671724 TI - Pathway Based Toxicology and Fit-for-Purpose Assays. AB - The field of toxicity testing for non-pharmaceutical chemicals is in flux with multiple initiatives in North America and the EU to move away from animal testing to mode-of-action based in vitro assays. In this arena, there are still obstacles to overcome, such as developing appropriate cellular assays, creating pathway based dose-response models and refining in vitro-in vivo extrapolation (IVIVE) tools. Overall, it is necessary to provide assurances that these new approaches are adequately protective of human and ecological health. Another major challenge for individual scientists and regulatory agencies is developing a cultural willingness to shed old biases developed around animal tests and become more comfortable with mode-of-action based assays in human cells. At present, most initiatives focus on developing in vitro alternatives and assessing how well these alternative methods reproduce past results related to predicting organism level toxicity in intact animals. The path forward requires looking beyond benchmarking against high dose animal studies. We need to develop targeted cellular assays, new cell biology-based extrapolation models for assessing regions of safety for chemical exposures in human populations, and mode-of-action based approaches which are constructed on an understanding of human biology. Furthermore, it is essential that assay developers have the flexibility to 'validate' against the most appropriate mode-of-action data rather than against apical endpoints in high dose animal studies. This chapter demonstrates the principles of fit-for-purpose assay development using pathway-targeted case studies. The projects include p53-mdm2-mediated DNA-repair, estrogen receptor mediated cell proliferation and PPARalpha receptor-mediated liver responses. PMID- 27671725 TI - Evidence-Based Toxicology. AB - Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century. PMID- 27671726 TI - Validation of Transcriptomics-Based In Vitro Methods. AB - The field of transcriptomics has expanded rapidly during the last decades. This methodology provides an exceptional framework to study not only molecular changes underlying the adverse effects of a given compound, but also to understand its Mode of Action (MoA). However, the implementation of transcriptomics-based tests within the regulatory arena is not a straightforward process. One of the major obstacles in their regulatory implementation is still the interpretation of this new class of data and the judgment of the level of confidence of these tests. A key element in the regulatory acceptance of transcriptomics-based tests is validation, which still represents a major challenge. Although important advances have been made in the development and standardisation of such tests, to date there is limited experience with their validation. Taking into account the experience acquired so far, this chapter describes those aspects that were identified as important in the validation process of transcriptomics-based tests, including the assessment of standardisation, reliability and relevance. It also critically discusses the challenges posed to validation in relation to the specific characteristics of these approaches and their application in the wider context of testing strategies. PMID- 27671727 TI - Ensuring the Quality of Stem Cell-Derived In Vitro Models for Toxicity Testing. AB - Quality control of cell cultures used in new in vitro toxicology assays is crucial to the provision of reliable, reproducible and accurate toxicity data on new drugs or constituents of new consumer products. This chapter explores the key scientific and ethical criteria that must be addressed at the earliest stages of developing toxicology assays based on human pluripotent stem cell (hPSC) lines. It also identifies key considerations for such assays to be acceptable for regulatory, laboratory safety and commercial purposes. Also addressed is the development of hPSC-based assays for the tissue and cell types of greatest interest in drug toxicology. The chapter draws on a range of expert opinion within the European Commission/Cosmetics Europe-funded alternative testing cluster SEURAT-1 and consensus from international groups delivering this guidance such as the International Stem Cell Banking Initiative. Accordingly, the chapter summarizes the most up-date best practices in the use and quality control of human Pluripotent Stem Cell lines in the development of in vitro toxicity assays from leading experts in the field. PMID- 27671728 TI - Validation of Bioreactor and Human-on-a-Chip Devices for Chemical Safety Assessment. AB - Equipment and device qualification and test assay validation in the field of tissue engineered human organs for substance assessment remain formidable tasks with only a few successful examples so far. The hurdles seem to increase with the growing complexity of the biological systems, emulated by the respective models. Controlled single tissue or organ culture in bioreactors improves the organ specific functions and maintains their phenotypic stability for longer periods of time. The reproducibility attained with bioreactor operations is, per se, an advantage for the validation of safety assessment. Regulatory agencies have gradually altered the validation concept from exhaustive "product" to rigorous and detailed process characterization, valuing reproducibility as a standard for validation. "Human-on-a-chip" technologies applying micro-physiological systems to the in vitro combination of miniaturized human organ equivalents into functional human micro-organisms are nowadays thought to be the most elaborate solution created to date. They target the replacement of the current most complex models-laboratory animals. Therefore, we provide here a road map towards the validation of such "human-on-a-chip" models and qualification of their respective bioreactor and microchip equipment along a path currently used for the respective animal models. PMID- 27671729 TI - Integrated Approaches to Testing and Assessment. AB - In this chapter, we explain how Integrated Approaches to Testing and Assessment (IATA) offer a means of integrating and translating the data generated by toxicity testing methods, thereby serving as flexible and suitable tools for toxicological decision making in the twenty-first century. In addition to traditional in vitro and in vivo testing methods, IATA are increasingly incorporating newly developed in vitro systems and measurement technologies such as high throughput screening and high content imaging. Computational approaches are also being used in IATA development, both as a means of generating data (e.g. QSARs), interpreting data (bioinformatics and chemoinformatics), and as a means of integrating multiple sources of data (e.g. expert systems, bayesian models). Decision analytic methods derived from socioeconomic theory can also play a role in developing flexible and optimal IATA solutions. Some of the challenges involved in the development, validation and implementation of IATA are also discussed. PMID- 27671731 TI - Evolving the Principles and Practice of Validation for New Alternative Approaches to Toxicity Testing. AB - Validation is essential for the translation of newly developed alternative approaches to animal testing into tools and solutions suitable for regulatory applications. Formal approaches to validation have emerged over the past 20 years or so and although they have helped greatly to progress the field, it is essential that the principles and practice underpinning validation continue to evolve to keep pace with scientific progress. The modular approach to validation should be exploited to encourage more innovation and flexibility in study design and to increase efficiency in filling data gaps. With the focus now on integrated approaches to testing and assessment that are based on toxicological knowledge captured as adverse outcome pathways, and which incorporate the latest in vitro and computational methods, validation needs to adapt to ensure it adds value rather than hinders progress. Validation needs to be pursued both at the method level, to characterise the performance of in vitro methods in relation their ability to detect any association of a chemical with a particular pathway or key toxicological event, and at the methodological level, to assess how integrated approaches can predict toxicological endpoints relevant for regulatory decision making. To facilitate this, more emphasis needs to be given to the development of performance standards that can be applied to classes of methods and integrated approaches that provide similar information. Moreover, the challenge of selecting the right reference chemicals to support validation needs to be addressed more systematically, consistently and in a manner that better reflects the state of the science. Above all however, validation requires true partnership between the development and user communities of alternative methods and the appropriate investment of resources. PMID- 27671730 TI - International Harmonization and Cooperation in the Validation of Alternative Methods. AB - The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing. PMID- 27671733 TI - Amygdala-ventral striatum circuit activation decreases long-term fear. AB - In humans, activation of the ventral striatum, a region associated with reward processing, is associated with the extinction of fear, a goal in the treatment of fear-related disorders. This evidence suggests that extinction of aversive memories engages reward-related circuits, but a causal relationship between activity in a reward circuit and fear extinction has not been demonstrated. Here, we identify a basolateral amygdala (BLA)-ventral striatum (NAc) pathway that is activated by extinction training. Enhanced recruitment of this circuit during extinction learning, either by pairing reward with fear extinction training or by optogenetic stimulation of this circuit during fear extinction, reduces the return of fear that normally follows extinction training. Our findings thus identify a specific BLA-NAc reward circuit that can regulate the persistence of fear extinction and point toward a potential therapeutic target for disorders in which the return of fear following extinction therapy is an obstacle to treatment. PMID- 27671732 TI - Global genetic diversity of Aedes aegypti. AB - Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co-occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub-Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans-Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations. PMID- 27671735 TI - Microbial contributions to subterranean methane sinks. AB - Sources and sinks of methane (CH4 ) are critical for understanding global biogeochemical cycles and their role in climate change. A growing number of studies have reported that CH4 concentrations in cave ecosystems are depleted, leading to the notion that these subterranean environments may act as sinks for atmospheric CH4 . Recently, it was hypothesized that this CH4 depletion may be caused by radiolysis, an abiotic process whereby CH4 is oxidized via interactions with ionizing radiation derived from radioactive decay. An alternate explanation is that the depletion of CH4 concentrations in caves could be due to biological processes, specifically oxidation by methanotrophic bacteria. We theoretically explored the radiolysis hypothesis and conclude that it is a kinetically constrained process that is unlikely to lead to the rapid loss of CH4 in subterranean environments. We present results from a controlled laboratory experiment to support this claim. We then tested the microbial oxidation hypothesis with a set of mesocosm experiments that were conducted in two Vietnamese caves. Our results reveal that methanotrophic bacteria associated with cave rocks consume CH4 at a rate of 1.3-2.7 mg CH4 . m-2 . d-1 . These CH4 oxidation rates equal or exceed what has been reported in other habitats, including agricultural systems, grasslands, deciduous forests, and Arctic tundra. Together, our results suggest that depleted concentrations of CH4 in caves are most likely due to microbial activity, not radiolysis as has been recently claimed. Microbial methanotrophy has the potential to oxidize CH4 not only in caves, but also in smaller-size open subterranean spaces, such as cracks, fissures, and other pores that are connected to and rapidly exchange with the atmosphere. Future studies are needed to understand how subterranean CH4 oxidation scales up to affect local, regional, and global CH4 cycling. PMID- 27671734 TI - Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery. AB - Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination. PMID- 27671736 TI - Plasmodium falciparum infection in febrile Congolese children: prevalence of clinical malaria 10 years after introduction of artemisinin-combination therapies. AB - OBJECTIVES: To investigate the proportion of malaria infection in febrile children consulting a paediatric hospital in Brazzaville, to determine the prevalence of submicroscopic malaria infection, to characterise Plasmodium falciparum infection and compare the prevalence of uncomplicated P. falciparum malaria according to haemoglobin profiles. METHODS: Blood samples were collected from children aged <10 years with an axillary temperature >=37.5 degrees C consulting the paediatric ward of Marien Ngouabi Hospital in Brazzaville. Parasite density was determined and all samples were screened for P. falciparum by nested polymerase chain reaction (PCR) using the P. falciparum msp-2 marker to detect submicroscopic infections and characterise P. falciparum infection. Sickle cell trait was screened by PCR. RESULTS: A total of 229 children with fever were recruited, of whom 10% were diagnosed with uncomplicated malaria and 21% with submicroscopic infection. The mean parasite density in children with uncomplicated malaria was 42 824 parasites/MUl of blood. The multiplicity of infection (MOI) was 1.59 in children with uncomplicated malaria and 1.69 in children with submicroscopic infection. The mean haemoglobin level was 10.1 +/- 1.7 for children with uncomplicated malaria and 12.0 +/- 8.6 for children with submicroscopic infection. About 13% of the children harboured the sickle cell trait (HbAS); the rest had normal haemoglobin (HbAA). No difference in prevalence of uncomplicated malaria and submicroscopic infection, parasite density, haemoglobin level, MOI and P. falciparum genetic diversity was observed according to haemoglobin type. CONCLUSION: The low prevalence of uncomplicated malaria in febrile Congolese children indicates the necessity to investigate carefully other causes of fever. PMID- 27671738 TI - Differential Counting of Asbestos Using Phase Contrast and Fluorescence Microscopy. AB - Considering the increasing use of various asbestos substitutes, asbestos risk management in many industries may require accurate techniques for detecting and distinguishing asbestos from non-asbestos fibers. Using fluorescently labeled asbestos-binding proteins, we previously developed a novel method for detection and counting of asbestos fibers under fluorescence microscopy (FM). This method can provide speedy, on-site detection and identification of the asbestos fibers and has higher sensitivity than phase contrast microscopy (PCM). However, current asbestos exposure limits are derived from risk assessments based on epidemiological studies that were conducted using PCM fiber counts. Therefore, the sensitivity of asbestos testing should be maintained at PCM level to properly assess compliance with these limit values. Here, we developed and tested a novel application of FM as a differential counting method that complements PCM analysis and is fully compatible with the PCM-based epidemiological data. In the combined PCM-FM method, the fluorescent asbestos-binding probe is applied prior to filter clearing. The method makes it possible to easily switch between two microscopic techniques while analyzing the same fields of view: PCM is used for counting fibers, and FM for differentiating asbestos from non-asbestos fibers. Using airborne dust samples from demolition sites in Japan, we compared PCM-FM with scanning electron microscopy (SEM)-based differential counting method. Statistical analysis indicated a slight conservative bias of PCM-FM method, combined with relatively high variability across the full range of fiber concentrations in our sample set. Using correlative microscopy, we also evaluated the specificity of FM staining, which is a potential cause of variability between the two methods. The energy-dispersive X-ray analysis indicated that ~95% of fluorescently stained fibers in the demolition site samples were correctly identified as asbestos. While further research is needed to fully clarify the causes of variability between FM- and SEM-based differential counting, PCM-FM could be used for rapid and selective detection of asbestos fibers in field samples. PMID- 27671737 TI - Is Early Appropriate Care of axial and femoral fractures appropriate in multiply injured elderly trauma patients? AB - BACKGROUND: Previous work established resuscitation parameters that minimize complications with early fracture management. This Early Appropriate Care (EAC) protocol was applied to patients with advanced age to determine if they require unique parameters to mitigate complications. METHODS: Between October 2010 and March 2013, 376 consecutive skeletally mature patients with unstable fractures of the pelvis, acetabulum, thoracolumbar spine, and/or proximal or diaphyseal femur fractures were treated at a level I trauma center and were prospectively studied. Patients aged <=30 years (n = 114), 30 to 60 years (n = 184), and >=60 years (n = 37) with Injury Severity Scores (ISS) >=16 and unstable fractures of the pelvis, acetabulum, spine, and/or diaphyseal femur were treated within 36 h, provided they showed evidence of adequate resuscitation. ISS, Glasgow Coma Scale (GCS), and American Society of Anesthesiologists (ASA) classification were determined. Lactate, pH, and base excess (BE) were measured at 8-h intervals. Complications included pneumonia, pulmonary embolism (PE), acute renal failure, acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), deep vein thrombosis, infection, sepsis, and death. RESULTS: Patients <=30 years old (y/o) were more likely to sustain gunshot wounds (p = 0.039), while those >=60 y/o were more likely to fall from a height (p = 0.002). Complications occurred at similar rates for patients <=30 y/o, 30 to 60 y/o, and >=60 y/o. There were no differences in lactate, pH, or BE at the time of surgery. For patients <=30 y/o, there were increased overall complications if pH was <7.30 (p = 0.042) or BE < 6.0 (p = 0.049); patients >=60 y/o demonstrated more sepsis if BE was <-6.0 (p = 0.046). CONCLUSIONS: EAC aims to definitively manage axial and femoral shaft fractures once patients have been adequately resuscitated to minimize complications. EAC is associated with comparable complication rates in young and elderly patients. Further study is warranted with a larger sample to further validate EAC in elderly patients. LEVEL OF EVIDENCE: level II prospective, comparative study. PMID- 27671739 TI - Excavation of Precious-Metal-Based Alloy Nanoparticles for Efficient Catalysis. AB - Methods have recently been developed for the synthesis of excavated alloy nanoparticles. However, various challenges still need to be overcome for a broad range of excavated nanoparticles with different sizes, surface structures, compositions, and constituent elements to be available for chemical and energy transformations through thermal catalysis and electrocatalysis. PMID- 27671741 TI - The potential role of polyphenols in the modulation of skin cell viability by Aspalathus linearis and Cyclopia spp. herbal tea extracts in vitro. AB - OBJECTIVES: The relationship between polyphenol constituents, antioxidant properties of aqueous and methanol extracts of green tea (Camellia sinensis), the herbal teas, rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.), against skin cell viability was investigated in vitro. METHODS: The effect of extracts, characterised in terms of polyphenol content and antioxidant properties, on cell viability of premalignant, normal and malignant skin cells was determined. KEY FINDINGS: Phenolic composition, particularly high levels of potent antioxidants, of rooibos and green tea methanol extracts was associated with a strong reduction in cell viability specifically targeting premalignant cells. In contrast, the aqueous extracts of Cyclopia spp. were more effective in reducing cell viability. This correlated with a relatively high flavanol/proanthocyanidin content and ABTS radical cation scavenging capacity. The major green tea flavanol (epigallocatechin gallate) and rooibos dihydrochalcone (aspalathin) exhibited differential effects against cell viability, while the major honeybush xanthone (mangiferin) and flavanone (hesperidin) lacked any effect presumably due to a cytoprotective effect. The underlying mechanisms against skin cell viability are likely to involve mitochondrial dysfunction resulting from polyphenol-iron interactions. CONCLUSIONS: The polyphenol constituents and antioxidant parameters of herbal tea extracts are useful tools to predict their activity against skin cell survival in vitro and potential chemopreventive effects in vivo. PMID- 27671742 TI - Study protocol of an RCT of EMOTION: An indicated intervention for children with symptoms of anxiety and depression. AB - BACKGROUND: High levels of anxiety and depression are common psychological symptoms among children and adolescents. These symptoms affect young people in multiple life domains and are possible precursors of long-term psychological distress. Despite relatively high prevalence, few children with emotional problems are referred for clinical treatment, indicating the need for systematic prevention. The primary aim of this study is to evaluate an indicated preventive intervention, EMOTION Coping Kids Managing Anxiety and Depression (EMOTION), to reduce high levels of anxiety and depressive symptoms. METHODS/DESIGN: This is a clustered randomized controlled trial involving 36 schools, which are assigned to one of two conditions: (a) group cognitive behavioral intervention EMOTION or (b) treatment as usual (TAU). Assessments will be undertaken at pre-, mid - intervention, post-, and one year after intervention. The children (8-11 years old) complete self-report questionnaires. Parents and teachers report on children. The primary outcome will be changes in depressive and anxiety symptoms as measured by the Short Mood and Feelings Questionnaire (SMFQ) and Multidimensional Anxiety Scale for Children (MASC) respectively. Secondary outcomes will be changes in self-esteem, quality of life, and school and daily functioning. Observers will assess implementation quality with ratings of fidelity based on video recordings of group leaders leading the EMOTION group sessions. DISCUSSION: The present study is an important contribution to the field regarding working with children with symptoms of anxiety and depression. The results of this study will provide an indication whether or not the EMOTION program is an effective intervention for the prevention of later depression and/or anxiety in children. The study will also provide information about the EMOTION program's effect on quality of life, self-esteem, and school functioning of the children participating in the study. Finally, the project will provide insight into implementation of an indicated intervention for school-aged children within Norwegian health, education, and mental health services. TRIAL REGISTRATION: Clinical Trials NCT02340637 , Registered on June 12, 2014, last updated on January 15, 2015. Retrospectively registered. PMID- 27671740 TI - Revisiting the membrane-centric view of diabetes. AB - Fundamental questions remain unresolved in diabetes: What is the actual mechanism of glucose toxicity? Why is there insulin resistance in type 2 diabetes? Why do diets rich in sugars or saturated fatty acids increase the risk of developing diabetes? Studying the C. elegans homologs of the anti-diabetic adiponectin receptors (AdipoR1 and AdipoR2) has led us to exciting new discoveries and to revisit what may be termed "The Membrane Theory of Diabetes". We hypothesize that excess saturated fatty acids (obtained through a diet rich in saturated fats or through conversion of sugars into saturated fats via lipogenesis) leads to rigid cellular membranes that in turn impair insulin signalling, glucose uptake and blood circulation, thus creating a vicious cycle that contributes to the development of overt type 2 diabetes. This hypothesis is supported by our own studies in C. elegans and by a wealth of literature concerning membrane composition in diabetics. The purpose of this review is to survey this literature in the light of the new results, and to provide an admittedly membrane-centric view of diabetes. PMID- 27671743 TI - Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio > 38: comparison of performance at 31-34 vs 35-37 weeks' gestation. AB - OBJECTIVE: To compare the performance of screening by soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio > 38 for the prediction of delivery with pre-eclampsia (PE) at < 1 week and < 4 weeks from assessment when the test is carried out at 31-34 vs 35-37 weeks' gestation. METHODS: This was a prospective observational study in women attending a third-trimester ultrasound scan as part of routine pregnancy care; the visit was at 30-34 weeks' gestation in the first phase of the study and at 35-37 weeks in the second phase. Serum sFlt-1 and PlGF were measured and their ratio calculated. We estimated the detection rate (DR) and false-positive rate (FPR) of sFlt-1/PlGF ratio > 38 for predicting delivery with PE at < 1 week and < 4 weeks after assessment and compared the performance of screening when the test was carried out at 31 + 0 to 33 + 6 vs 35 + 0 to 36 + 6 weeks' gestation. RESULTS: The study population included 8063 singleton pregnancies that were examined at 31-34 weeks and 3703 at 35-37 weeks. Delivery with PE occurred at < 1, < 4 and >= 4 weeks from assessment in five (0.1%), 29 (0.4%) and 202 (2.5%) women assessed at 31-34 weeks, respectively, and in seven (0.2%), 39 (1.1%) and 21 (0.6%) of those assessed at 35-37 weeks. In women without PE, the median sFlt-1/PlGF ratio increased with gestational age at screening and a ratio of 38 was just below the 99th percentile at 32 weeks' gestation and just below the 90th percentile at 36 weeks. In the two gestational windows, the DR of PE delivering < 4 weeks from assessment was similar (75.9% (95% CI, 56.5-89.7%) vs 79.5% (95% CI, 63.5-90.7%)), but the FPR was substantially lower at 31-34 weeks than at 35-37 weeks (1.7% (95% CI, 1.4 2.0%) vs 9.6% (95% CI, 8.7-10.6%)). The number of cases with PE delivering < 1 week from assessment was small, but similarly, in the two gestational windows, the DR was comparable (80.0% (95% CI, 28.4-99.5%) vs 85.7% (95% CI, 42.1-99.6%)), and the FPR was substantially lower at 31-34 weeks than at 35-37 weeks (1.9% (95% CI, 1.6-2.2%) vs 10.2% (95% CI, 9.3-11.3%)). CONCLUSION: The performance of sFlt 1/PlGF ratio > 38 in the prediction of delivery with PE at < 1 and < 4 weeks from assessment is substantially different when the assessment is at 31-34 weeks' gestation compared to at 35-37 weeks. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27671744 TI - Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer. AB - Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study was to evaluate the feasibility of STER using methylene blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors >= 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia. PMID- 27671745 TI - Unveiling the propagation dynamics of self-accelerating vector beams. AB - We study theoretically and experimentally the varying polarization states and intensity patterns of self-accelerating vector beams. It is shown that as these beams propagate, the main intensity lobe and the polarization singularity gradually drift apart. Furthermore, the propagation dynamics can be manipulated by controlling the beams' acceleration coefficients. We also demonstrate the self healing dynamics of these accelerating vector beams for which sections of the vector beam are being blocked by an opaque or polarizing obstacle. Our results indicate that the self-healing process is almost insensitive for the obstacles' polarization direction. Moreover, the spatial polarization structure also shows self- healing properties, and it is reconstructed as the beam propagates further beyond the perturbation plane. These results open various possibilities for generating, shaping and manipulating the intensity patterns and space variant polarization states of accelerating vector beams. PMID- 27671746 TI - The use of adjuvant chemotherapy for pancreatic cancer varies widely between hospitals: a nationwide population-based analysis. AB - Adjuvant chemotherapy after pancreatoduodenectomy for pancreatic cancer is currently considered standard of care. In this nationwide study, we investigated which characteristics determine the likelihood of receiving adjuvant chemotherapy and its effect on overall survival. The data were obtained from the Netherlands Cancer Registry. All patients alive 90 days after pancreatoduodenectomy for M0 pancreatic cancer between 2008 and 2013 in the Netherlands were included in this study. The likelihood to receive adjuvant chemotherapy was analyzed by multilevel logistic regression analysis and differences in time-to-first-chemotherapy were tested for significance by Mann-Whitney U test. Overall survival was assessed by Kaplan-Meier method and Cox regression analysis. Of the 1195 patients undergoing a pancreatoduodenectomy for pancreatic cancer, 642 (54%) patients received adjuvant chemotherapy. Proportions differed significantly between the 19 pancreatic centers, ranging from 26% to 74% (P < 0.001). Median time-to-first chemotherapy was 6.7 weeks and did not differ between centers. Patients with a higher tumor stage, younger age, and diagnosed more recently were more likely to receive adjuvant treatment. The 5-year overall survival was significantly prolonged in patients treated with adjuvant chemotherapy-23% versus 17%, log-rank = 0.01. In Cox regression analysis, treatment with adjuvant chemotherapy significantly prolonged survival compared with treatment without adjuvant chemotherapy. The finding that elderly patients and patients with a low tumor stage are less likely to undergo treatment needs further attention, especially since adjuvant treatment is known to prolong survival in most of these patients. PMID- 27671747 TI - A Porphyrin-Based Conjugated Polymer for Highly Efficient In Vitro and In Vivo Photothermal Therapy. AB - Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor-acceptor (D-A) structured porphyrin-containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D-A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state-of-art porphyrin-based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 * 104 m-1 cm-1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer-based photothermal therapeutic materials for potential personalized theranostic nanomedicine. PMID- 27671748 TI - Efficacy and mechanisms of imagery rescripting and imaginal exposure for nightmares: study protocol for a randomized controlled trial. AB - BACKGROUND: Recurrent nightmares can effectively be treated with cognitive behavioral techniques such as imagery rehearsal therapy, which involves imagery rescripting (IR) of nightmares, and imaginal exposure (IE) therapy. However, the underlying mechanisms of these treatments remain largely unknown. To investigate this, we identified a number of variables that might mediate the therapeutic effect of rescripting-based and/or exposure-based therapies. Also, to control for the possible confounding influence of (other) treatment components, we designed two stripped-down treatment protocols, which primarily consist of either (1) rescripting of, or (2) exposure to, the nightmare content. In a randomized controlled trial, we aim to investigate the therapeutic efficacy of these stripped-down IR and IE treatments, and explore their working mechanisms. METHOD: Three weekly sessions of either IR or IE will be compared to a waiting-list control group. Ninety participants suffering from nightmare disorder will be included and randomly allocated to one of the three groups. The primary clinical outcome measures are nightmare frequency and distress caused by nightmares. Secondary clinical outcome measures include sleep complaints, dysfunctional beliefs about nightmares, and posttraumatic stress symptom severity. Outcomes will be assessed weekly from week 1 (pre-assessment) to week 5 (post-assessment). Online follow-up assessments will take place at 3 and 6 months after post assessment. In order to investigate temporal relationships between mediators and outcome, we will measure the proposed mediators of the treatment effect 1 day after each outcome assessment (but not after the follow-ups). Mediators include nightmare distress and valence, mastery of the nightmare content, predictability, controllability, and tolerability of emotions elicited by nightmares, as well as sleep quality. DISCUSSION: The proposed trial allows us to investigate the efficacy of IR and IE as intervention techniques for the treatment of nightmares, and to explore mediators of their respective therapeutic effects. The results may advance our understanding of nightmare therapies by identifying possible mechanisms of psychological treatments for chronic nightmares. Moreover, the results of the proposed study might provide useful knowledge about the working mechanism of rescripting-based and exposure-based treatments in general. TRIAL REGISTRATION: Netherlands Trial Register ( NTR4951 ), registered on 14 December 2014. PMID- 27671749 TI - Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein. AB - The protein alpha-synuclein (alphaS) self-assembles into toxic beta-sheet aggregates in Parkinson's disease, while it is proposed that alphaS forms soluble alpha-helical multimers in healthy neurons. Here, we have made alphaS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single molecule Forster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of alphaS form less multimers than wild-type alphaS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of alphaS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during alphaS fibrillation. PMID- 27671750 TI - Concise Review: Stem Cell Population Biology: Insights from Hematopoiesis. AB - Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe. The application of population dynamics to biology is amongst the oldest applications of mathematics to biology, and the population dynamics perspective continues to offer much today. Here we describe the impact that such a perspective has made in the field of stem cell biology. Using hematopoietic stem cells as our model system, we discuss the approaches that have been used to study their key properties, such as capacity for self-renewal, differentiation, and cell fate lineage choice. We will also discuss the relevance of population dynamics in models of stem cells and cancer, where competition naturally emerges as an influential factor on the temporal evolution of cell populations. Stem Cells 2017;35:80-88. PMID- 27671752 TI - Effects of Volume, Pitch, and Phonation Type on Oscillation Initiation and Termination Phases Investigated With High-speed Videoendoscopy. AB - OBJECTIVES: This study aimed to investigate the effects of varying volume, pitch, and phonation types on the initiation and termination phases of vocal fold oscillation using high-speed digital videoendoscopy. Specifically, it addressed the effects of the variation of volume, pitch, and phonation type (normal, pressed, and breathy) on the transient duration of the vibrating glottal length (length transient duration, Tlen), the transient duration of the glottal area waveform (area transient duration, Tarea), the time offset between the beginning (or the end) of the full-length vibration and the full-amplitude vibration, TDelta, and the variation of the fundamental frequency during the vocal fold oscillation initiation and termination segments (pitch instability, %PI). METHODS: A female subject with no voice problem produced voices with varying pitch and loudness, including comfortable pitch and comfortable loudness, normal pitch loud, high pitch and comfortable loudness, and high pitch and loud. Breathy and pressed phonations were also recorded. Each of the six phonation types was recorded six times, which resulted in 72 transient segments (each recording included both initiation and termination phases). Mixed model statistical analyses were employed to the five objective high-speed digital videoendoscopy parameters. RESULTS: Preliminary findings demonstrated significant findings for voice type effects for the length and area transient durations for the oscillation initiation segment but not for the oscillation termination segment. CONCLUSIONS: This study demonstrates that voice types appear to influence vibration initiation patterns more than the vibration termination patterns. PMID- 27671751 TI - An Excised Canine Model of Anterior Glottic Web and Its Acoustic, Aerodynamic, and High-speed Measurements. AB - OBJECTIVES: This study aims to build an excised anterior glottic web (AGW) model and study the basic voice-related mechanisms of the AGW through investigating the acoustic, aerodynamic, and vibratory properties. STUDY DESIGN AND METHODS: Overall, four conditions were tested for each of the eight canine larynges used. At baseline, 10%, 20%, and 33% occlusion (as determined by the placement of the suture), acoustic, aerodynamic, and high-speed video data were collected while each larynx was phonated in a soundproof booth. RESULTS: The phonation threshold pressure (PTP) and the phonation threshold flow significantly increased as percent occlusion increased (P < 0.001). There were significant increases in jitter % and shimmer % from baseline group to AGW model groups at PTP, 1.25 PTP, and 1.5 PTP (P = 0.039, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively). The fundamental frequency significantly increased as percent occlusion increased at all given pressures (P < 0.001). Correlation dimension (D2) was significantly higher in the AGW model groups than in the baseline group at PTP, 1.25 PTP, and 1.5 PTP (P = 0.002, P < 0.001, P = 0.01, respectively). High-speed videos revealed that, the left phase shift in the AGW model groups compared with the baseline at 1.25 PTP was significant (P = 0.027) and right phase shift at 1.5 PTP (P < 0.001). CONCLUSIONS: We presented an anatomically similar model of a type 1 AGW and confirmed its validity through aerodynamic, acoustic, and high-speed video analysis in our study. We observed and investigated the glottic web movement, which may be a new explanation for the pathologic voice-related mechanism of AGW. PMID- 27671754 TI - Gastrectomy is Associated with an Increased Risk of Pyogenic Liver Abscess: A 13 Year Nationwide Cohort Study. AB - Whether patients who have undergone gastrectomy are at a high risk of developing pyogenic liver abscess (PLA) remains debatable. From the inpatient claims records of Taiwan's National Health Insurance Research Database, we identified 33 834 patients with a history of 2000-2010 and135 336 controls without a history of gastrectomy. The 2cohorts were matched by age, sex, and admission year and followed-up until the end of 2011 for estimating the risk of PLA. Overall, the incidence of PLA was 3.5-fold higher in the gastrectomy cohort than in the control cohort (21.6 vs 5.76 per 10 000 person-y). The adjusted hazard ratio (aHR) for the gastrectomy cohort obtained using the multivariate Cox proportional hazards regression model was 3.08 (95% confidence interval [CI] = 2.60-3.64). An elevated post gastrectomy PLA risk was observed in both men and women. Age specific data revealed that the aHR for the gastrectomy cohort, compared with the control cohort, was the highest in patients younger than 50 years (aHR = 5.16, 95% CI = 2.96-9.01). An addition analysis showed that the gastrectomy cohort exhibited an elevated PLA risk regardless of whether the patients underwent total or partial gastrectomy. Patients with a history of gastrectomy exhibit a high risk of PLA. PMID- 27671753 TI - Silencing of CD47 and SIRPalpha by Polypurine reverse Hoogsteen hairpins to promote MCF-7 breast cancer cells death by PMA-differentiated THP-1 cells. AB - BACKGROUND: In the context of tumor immunology, tumor cells have been shown to overexpress CD47, an anti-phagocytic signal directed to macrophages to escape from phagocytosis by interacting with Signal Regulatory Protein alpha SIRPalpha. In the present work, we designed Polypurine reverse Hoogsteen hairpins, PPRHs, to silence the expression of CD47 in tumor cells and SIRPalpha in macrophages with the aim to eliminate tumor cells by macrophages in co-culture experiments. METHODS: THP-1 cells were differentiated to macrophages with PMA. The mRNA levels of differentiation markers CD14 and Mcl-1 mRNA and pro-inflammatory cytokines (IL 1beta, IL-18, IL-6, IL-8 and TNF-alpha) were measured by qRT-PCR. The ability of PPRHs to silence CD47 and SIRPalpha was evaluated at the mRNA level by qRT-PCR and at the protein level by Western Blot. Macrophages were co-cultured with tumor cells in the presence of PPRHs to silence CD47 and/or SIRPalpha. Cell viability was assessed by MTT assays. RESULTS: THP-1 cells differentiated to macrophages with PMA showed an increase in macrophage surface markers (CD14, Mcl-1) and pro inflammatory cytokines (IL-1beta, IL-18, IL-6, IL-8 and TNF-alpha). PPRHs were able to decrease both CD47 expression in MCF-7 cell line and SIRPalpha expression in macrophages at the mRNA and protein levels. In the presence of PPRHs, MCF-7 cells were eliminated by macrophages in co-culture experiments, whereas they survived in the absence of PPRHs. CONCLUSIONS: Our data support the usage of PPRHs to diminish CD47/SIRPalpha interaction by decreasing the expression of both molecules thus resulting in an enhanced killing of MCF-7 cells by macrophages, which might translate into beneficial effects in cancer therapy. These results indicate that PPRHs could represent a new approach with immunotherapeutic applications. PMID- 27671755 TI - Vitamin A prevents round spermatid nuclear damage and promotes the production of motile sperm during in vitro maturation of vitrified pre-pubertal mouse testicular tissue. AB - STUDY QUESTION: Does vitamin A (retinol, Rol) prevent round spermatid nuclear damage and increase the production of motile sperm during in vitro maturation of vitrified pre-pubertal mouse testicular tissue? SUMMARY ANSWER: The supplementation of an in vitro culture of ~0.75 mm3 testicular explants from pre pubertal mice with Rol enhances spermatogenesis progression during the first spermatogenic wave. WHAT IS KNOWN ALREADY: The production of functional spermatozoa in vitro has only been achieved in the mouse model and remains a rare event. Establishing an efficient culture medium for vitrified pre-pubertal testicular tissue is now a crucial step to improve the spermatic yield obtained in vitro. The role of Rol in promoting the differentiation of spermatogonia and their entry into meiosis is well established; however, it has been postulated that Rol is also required to support their full development into elongated spermatids. STUDY DESIGN, SIZE, DURATION: A total of 60 testes from 6.5 days post partum (dpp) mice were vitrified/warmed, cut into fragments and cultured for 30 days: 20 testes were used for light microscopy and histological analyses, 20 testes for DNA fragmentation assessment in round spermatids and 20 testes for induced sperm motility assessment. Overall, 16 testes of 6.5 dpp were used as in vitro fresh tissue controls and 12 testes of 36.5 dpp mice as in vivo controls. Testes were vitrified with the optimal solid surface vitrification procedure and cultured with an in vitro organ culture system until Day 30 (D30). Histological analysis, cell death, degenerating round spermatids, DNA fragmentation in round spermatids and induced sperm motility were assessed. Testosterone levels were measured in media throughout the culture by radioimmunoassay. MAIN RESULTS AND THE ROLE OF CHANCE: At D30, better tissue development together with higher differentiation of spermatogonial stem cells, and higher global cell division ability were observed for vitrified/warmed testicular fragments of ~0.75 mm3 with a culture medium supplemented with Rol compared to controls. During in vitro culture of vitrified pre-pubertal testicular tissue, Rol enhanced and maintained the entry of spermatogonia into meiosis and promoted a higher spermatic yield. Furthermore, decreased round spermatid nuclear alterations and DNA damage combined with induced sperm motility comparable to in vivo highlight the crucial role of Rol in the progression of spermatogenesis during the first wave. LIMITATIONS, REASONS FOR CAUTION: Despite our promising results, the culture media will have to be further improved and adapted within the context of a human application. WIDER IMPLICATIONS OF THE FINDINGS: The results have potential implications for the handling of human pre-pubertal testicular tissues cryopreserved for fertility preservation. However, because some alterations in round spermatids persist after in vitro culture with Rol, the procedure needs to be optimized before human application, bearing in mind that the murine and human spermatogenic processes differ in many respects. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by a Ph.D. grant from the Normandy University and a financial support from 'la Ligue nationale contre le cancer' (both awarded to L.D.), funding from Rouen University Hospital, Institute for Research and Innovation in Biomedicine (IRIB) and Agence de la Biomedecine. The authors declare that there is no conflict of interest. PMID- 27671757 TI - It Takes Vision to Prepare for Our Future. PMID- 27671756 TI - Clinical Features, Complications and Autoimmunity in Male Lichen Sclerosus. AB - Lichen sclerosus is a chronic inflammatory disease associated with substantial morbidity. Knowledge of the aetiology and progression of lichen sclerosus is therefore needed. In this cross-sectional study, 100 male patients diagnosed with lichen sclerosus were interviewed and examined. Since there is a possible link between lichen sclerosus and autoimmunity, blood tests were analysed for thyroid disease, antinuclear antibodies and antibodies to extracellular matrix protein 1, but autoimmunity was found to be infrequent. In 72 participants active genital lichen sclerosis was observed and complications were common; 27 patients had preputial constriction and 12 meatal engagement. In total, 13 patients needed a referral to the Department of Urology, including 1 patient with suspected penile cancer. In conclusion, despite available treatment with ultra-potent steroids and circumcision, lichen sclerosus in males is frequently complicated by phimosis and meatal stenosis. However, the disease can also go into remission, as seen in 27% of our patients. PMID- 27671758 TI - MyPlate at FNCE & Beyond: Join the Fun! PMID- 27671759 TI - Practice Paper of the Academy of Nutrition and Dietetics: Role of the Registered Dietitian Nutritionist in the Diagnosis and Management of Food Allergies. AB - Incidence of food allergy has increased significantly over the past decade and represents an important health issue for millions of Americans. Diagnosis of immunoglobulin E-mediated food allergies is sometimes difficult because blood and skin tests have high rates of false positives, and oral food challenges are uncommon due to the expense and potential for serious reactions. Accurate diagnosis is crucial to avoid unnecessary dietary restriction, especially in children. Because registered dietitian nutritionists often work independently, receiving referrals for dietary education and guidance for a patient who is followed by one or several other practitioners, navigating the data available and making the appropriate follow-up contact optimizes treatment. The purpose of this paper is to provide guidance to the registered dietitian nutritionists and nutrition and dietetics technician, registered on appropriate and evidence-based nutrition counseling for diagnosis and management of food allergies. PMID- 27671760 TI - Entry-Level Dietetics Practice Today: Results from the 2015 Commission on Dietetic Registration Entry-Level Dietetics Practice Audit. PMID- 27671761 TI - Distinctions in Entry-Level Registered Dietitian Nutritionist and Nutrition and Dietetics Technicians, Registered, Practice: Further Results from the 2015 Commission on Dietetic Registration Entry-Level Dietetics Practice Audit. PMID- 27671762 TI - Translating the Dietary Guidelines to Promote Behavior Change: Perspectives from the Food and Nutrition Science Solutions Joint Task Force. PMID- 27671763 TI - What Are the New Nutrition Standards for the Child and Adult Care Food Program? PMID- 27671764 TI - The mechanism of eutectic growth in highly anisotropic materials. AB - In the past 50 years, there has been increasing interest-both theoretically and experimentally-in the problem of pattern formation of a moving boundary, such as a solidification front. One example of pattern formation is that of irregular eutectic solidification, in which the solid-liquid interface is non-isothermal and the interphase spacing varies in ways that are poorly understood. Here, we identify the growth mode of irregular eutectics, using reconstructions from four dimensional (that is, time and space resolved) X-ray microtomography. Our results show that the eutectic growth process can be markedly different from that seen in previously used model systems and theories based on the ex situ analysis of microstructure. In light of our experimental findings, we present a coherent growth model of irregular eutectic solidification. PMID- 27671765 TI - Cardiac computed tomography for the detection of cardiac amyloidosis. PMID- 27671766 TI - Cost of Immediate Surgery Versus Non-operative Treatment for Trigger Finger in Diabetic Patients. AB - PURPOSE: As health care costs continue to rise, providers must increasingly identify and implement cost-effective practice measures without sacrificing quality of care. Corticosteroid injections are an established treatment for trigger finger; however, numerous clinical trials have documented the limited efficacy of these injections in the diabetic population. Furthermore, the most cost-effective treatment strategy for diabetic trigger finger has not been determined. The purpose of this study was to perform a decision analysis to identify the least costly strategy for effective treatment of diabetic trigger finger using existing evidence in the literature. METHODS: Four treatment strategies for diabetic trigger finger were identified: (1) 1 steroid injection followed by surgical release, (2) 2 steroid injections followed by surgical release, (3) immediate surgical release in the operating room, and (4) immediate surgical release in the clinic. A literature review was conducted to determine success rates of the different treatment strategies. Costing analysis was performed using our institutional reimbursement from Medicare. One-way sensitivity and threshold analysis was utilized to determine the least costly treatment strategy. RESULTS: The least costly treatment strategy was immediate surgical release in the clinic. In patients with insulin-dependent diabetes mellitus, this strategy results in a 32% and a 39% cost reduction when compared with treatment with 1 or 2 corticosteroid injections, respectively. For 1 or 2 corticosteroid injections to be the most cost-effective strategy, injection failure rates would need to be less than 36% and 34%, respectively. The overall cost of care for immediate surgical release in the clinic was $642. CONCLUSIONS: Diabetic trigger finger is a common problem faced by hand surgeons, with a variety of acceptable treatment algorithms. Management of diabetic trigger finger with immediate surgical release in the clinic is the most cost-effective treatment strategy, assuming a corticosteroid injection failure rate of at least 34%. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/decision III. PMID- 27671767 TI - Scaphoid Fractures: Nonunion and Malunion. AB - The treatment of scaphoid nonunion and malunions has undergone a considerable transition since the 1960 modification of Matti's technique by Russe.1 We present a review of articles with clear data on union rates and functional status to review the current methods of treatment for scaphoid nonunion and malunion. PMID- 27671768 TI - Risk Factors for 30-Day Postoperative Complications Following Open Reduction Internal Fixation of Proximal Ulna Fractures. AB - PURPOSE: Fractures of the proximal ulna are common injuries in the elderly population. These fractures can be managed nonsurgically or with open reduction internal fixation (ORIF). Whereas nonsurgical management may lead to a relative loss of elbow extension and to nonunion, ORIF carries a risk of complications. Although complications specific to the orthopedic intervention have been reported, few studies have identified postoperative systemic complications in this higher-risk group. The purposes of this study were to determine the rate of systemic complications in patients undergoing surgical fixation of proximal ulna fractures and to determine risk factors for complications. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program database for all cases of proximal ulna fracture ORIF between 2005 and 2013. Demographic, historical, and preoperative laboratory data and 30-day postoperative complications were recorded. Univariate and multivariable analyses were performed to identify independent risk factors for complications. RESULTS: A total of 650 patients met inclusion criteria. Within the 30-day postoperative period, 61 complications occurred in 45 patients (6.9%). Return to the operating room, which occurred in 19 patients (2.9%), was the most common major morbidity. American Society of Anesthesiologists class III or IV and dialysis dependence were independent risk factors for any complication. CONCLUSIONS: Proximal ulna fracture ORIF has a low rate of systemic complications. The most common morbidities are return to the operating room, blood transfusion, and urinary tract infections. Dialysis and American Society of Anesthesiologists class III or IV are independent risk factors for complications. These complications may be nonspecific and related more to the patient population than procedure. We believe that the relatively low risk of short-term complications makes operative treatment a suitable option even in elderly patients with multiple morbidities. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. PMID- 27671769 TI - Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies. AB - A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6 carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents. PMID- 27671770 TI - MnTE-2-PyP modulates thiol oxidation in a hydrogen peroxide-mediated manner in a human prostate cancer cell. AB - To improve the treatment of advanced prostate cancer, the development of effective and innovative antitumor agents is needed. Our previous work demonstrated that the ROS (reactive oxygen species) scavenger, MnTE-2-PyP, inhibited human prostate cancer growth and also inhibited prostate cancer migration and invasion. We showed that MnTE-2-PyP treatment altered the affinity of the histone acetyltransferase enzyme, p300, to bind to DNA. We speculate that this may be one mechanism by which MnTE-2-PyP inhibits prostate cancer progression. Specifically, MnTE-2-PyP decreased p300/HIF-1/CREB complex (p300/hypoxia-inducible factor-1/cAMP response element-binding protein) binding to a specific hypoxia-response element (HRE) motif within the plasminogen activator inhibitor-1 (PAI-1) gene promoter region, and consequently, repressed PAI-1 expression. However, it remains unclear how MnTE-2-PyP reduces p300 complex binding affinity to the promoter region of specific genes. In this study, we found that overexpression of Cu/ZnSOD (superoxide dismutase 1, SOD1) significantly suppressed PAI-1 gene expression and p300 complex binding to the promoter region of PAI-1 gene, just as was observed in cells treated with MnTE-2 PyP. Furthermore, catalase (CAT) overexpression rescued the inhibition of PAI-1 expression and p300 binding by MnTE-2-PyP. Taken together, the above findings suggest that hydrogen peroxide (H2O2) is likely the mediator through which MnTE-2 PyP inhibits the PAI-1 expression and p300 complex binding in PC3 cells. To confirm this, we measured the production of H2O2 following overexpression of SOD1 or catalase with MnTE-2-PyP treatment in the presence or absence of radiation. We found that MnTE-2-PyP increased the intracellular steady-state levels of H2O2 and increased nuclear H2O2 levels. As expected, catalase overexpression significantly decreased the levels of intracellular H2O2 induced by MnTE-2-PyP. We then determined if this increased H2O2 production could result in oxidized protein thiol groups. In the presence of MnTE-2-PyP, there was a significant increase in oxidized thiols in PC3 cell lysates and this was reversed with catalase overexpression. Specifically, we showed that p300 was oxidized after MnTE-2-PyP treatment, indicating that MnTE-2-PyP is creating a more oxidizing environment and this is altering the oxidation state of p300 thiol residues. Our data provide an in depth mechanism by which MnTE-2-PyP regulates gene transcription through induced H2O2 mediated oxidation of particular proteins, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in prostate cancer radiotherapy. PMID- 27671771 TI - Association of depression and anxiety status with 10-year cardiovascular disease incidence among apparently healthy Greek adults: The ATTICA Study. AB - Background Chronic stress frequently manifests with anxiety and/or depressive symptomatology and may have detrimental cardiometabolic effects over time. As such, recognising the potential links between stress-related psychological disorders and cardiovascular disease (CVD) is becoming increasingly important in cardiovascular epidemiology research. The primary aim of this study was to explore prospectively potential associations between clinically relevant depressive symptomatology and anxiety levels and the 10-year CVD incidence among apparently healthy Greek adults. Design A population-based, health and nutrition prospective survey. Methods In the context of the ATTICA Study (2002-2012), 853 adult participants without previous CVD history (453 men (45 +/- 13 years) and 400 women (44 +/- 18 years)) underwent psychological evaluations through validated, self-reporting depression and anxiety questionnaires. Results After adjustment for multiple established CVD risk factors, both reported depression and anxiety levels were positively and independently associated with the 10-year CVD incidence, with depression markedly increasing the CVD risk by approximately fourfold (adjusted odds ratio (95% confidence interval) 3.6 (1.3, 11) for depression status; 1.03 (1.0, 1.1) for anxiety levels). Conclusions Our findings indicate that standardised psychological assessments focusing on depression and anxiety should be considered as an additional and distinct aspect in the context of CVD preventive strategies that are designed and implemented by health authorities at the general population level. PMID- 27671772 TI - The renin-angiotensin-aldosterone system in heart failure for the non-specialist: the past, the present and the future. AB - Heart failure is one of the major public health challenges facing the Western world. Its prevalence is increasing as the population ages and modern techniques are implemented to manage cardiac disease. In response, there has been a sustained effort to develop novel strategies to address the high levels of associated morbidity and mortality. Indeed, agents that target the renin angiotensin-aldosterone system (RAAS) have transformed the way in which we manage heart failure. Despite this, mortality in heart failure is poorer than in many malignancies and a large burden of morbidity and recurrent hospitalisation remains. Here, we review the role of RAAS modulation within the field of systolic heart failure. In particular, we provide practical guidance on using current RAAS blockade agents and focus on the recent emergence of new agents that promise additional substantial benefit to those living with left ventricular systolic dysfunction. PMID- 27671773 TI - Characterization of heme oxygenase and biliverdin reductase gene expression in zebrafish (Danio rerio): Basal expression and response to pro-oxidant exposures. AB - While heme is an important cofactor for numerous proteins, it is highly toxic in its unbound form and can perpetuate the formation of reactive oxygen species. Heme oxygenase enzymes (HMOX1 and HMOX2) degrade heme into biliverdin and carbon monoxide, with biliverdin subsequently being converted to bilirubin by biliverdin reductase (BVRa or BVRb). As a result of the teleost-specific genome duplication event, zebrafish have paralogs of hmox1 (hmox1a and hmox1b) and hmox2 (hmox2a and hmox2b). Expression of all four hmox paralogs and two bvr isoforms were measured in adult tissues (gill, brain and liver) and sexually dimorphic differences were observed, most notably in the basal expression of hmox1a, hmox2a, hmox2b and bvrb in liver samples. hmox1a, hmox2a and hmox2b were significantly induced in male liver tissues in response to 96h cadmium exposure (20MUM). hmox2a and hmox2b were significantly induced in male brain samples, but only hmox2a was significantly reduced in male gill samples in response to the 96h cadmium exposure. hmox paralogs displayed significantly different levels of basal expression in most adult tissues, as well as during zebrafish development (24 to 120hpf). Furthermore, hmox1a, hmox1b and bvrb were significantly induced in zebrafish eleutheroembryos in response to multiple pro-oxidants (cadmium, hemin and tert butylhydroquinone). Knockdown of Nrf2a, a transcriptional regulator of hmox1a, was demonstrated to inhibit the Cd-mediated induction of hmox1b and bvrb. These results demonstrate distinct mechanisms of hmox and bvr transcriptional regulation in zebrafish, providing initial evidence of the partitioning of function of the hmox paralogs. PMID- 27671776 TI - Phylogenetic analysis of rabies virus isolated from canids in North and Northeast Brazil. AB - Cases of canine rabies continue to occur in North and Northeast Brazil, and the number of notifications of rabies cases in wild canids has increased as a result of the expansion of urban areas at the expense of areas with native vegetation. In light of this, we performed molecular characterization of rabies virus isolates from dogs and Cerdocyon thous from various states in North and Northeast Brazil. In all, 102 samples from dogs (n = 56) and Cerdocyon thous (n = 46) collected between 2006 and 2012 were used. The nucleotide sequences obtained for the N gene of rabies virus were analyzed, and phylogenetic analysis revealed the presence of two distinct genetic lineages, one associated with canids and one with bats, and, within the canid cluster, two distinct sublineages circulating among dogs and Cerdocyon thous. In addition, phylogenetic groups associated with geographic region and fourteen cases of interspecific infection were observed among the isolates from canids. Our findings show that analysis of rabies virus lineages isolated from reservoirs such as canids must be constantly evaluated because the mutation rate is high. PMID- 27671775 TI - Cell lipid metabolism modulators 2-bromopalmitate, D609, monensin, U18666A and probucol shift discoidal HDL formation to the smaller-sized particles: implications for the mechanism of HDL assembly. AB - ATP-binding cassette transporter A1 (ABCA1) mediates formation of disc-shaped high-density lipoprotein (HDL) from cell lipid and lipid-free apolipoprotein A-I (apo A-I). Discoidal HDL particles are heterogeneous in physicochemical characteristics for reasons that are understood incompletely. Discoidal lipoprotein particles similar in characteristics and heterogeneity to cell-formed discoidal HDL can be reconstituted from purified lipids and apo A-I by cell-free, physicochemical methods. The heterogeneity of reconstituted HDL (rHDL) is sensitive to the lipid composition of the starting lipid/apo A-I mixture. To determine whether the heterogeneity of cell-formed HDL is similarly sensitive to changes in cell lipids, we investigated four compounds that have well-established effects on cell lipid metabolism and ABCA1-mediated cell cholesterol efflux. 2 Bromopalmitate, D609, monensin and U18666A decreased formation of the larger sized, but dramatically increased formation of the smaller-sized HDL. 2 Bromopalmitate did not appear to affect ABCA1 activity, subcellular localization or oligomerization, but induced dissolution of the cholesterol-phospholipid complexes in the plasma membrane. Arachidonic and linoleic acids shifted HDL formation to the smaller-sized species. Tangier disease mutations and inhibitors of ABCA1 activity wheat germ agglutinin and AG 490 reduced formation of both larger-sized and smaller-sized HDL. The effect of probucol was similar to the effect of 2-bromopalmitate. Taking rHDL formation as a paradigm, we propose that ABCA1 mutations and activity inhibitors reduce the amount of cell lipid available for HDL formation, and the compounds in the 2-bromopalmitate group and the polyunsaturated fatty acids change cell lipid composition from one that favors formation of the larger-sized HDL particles to one that favors formation of the smaller-sized species. PMID- 27671774 TI - DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients. AB - Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. PMID- 27671777 TI - Bustos virus, a new member of the negevirus group isolated from a Mansonia mosquito in the Philippines. AB - We isolated two distinct viruses from mosquitoes collected in Bustos, Bulacan province, Philippines, in 2009. These viruses show rapid replication and strong cytopathic effects in mosquito C6/36 cells. Whole-genome analysis of these viruses demonstrated that both viruses belong to the negevirus group. One of the viruses, from Culex vishunui mosquitoes, is a new strain of Negev virus. The other virus, from a Mansonia sp. mosquito, is a new negevirus designated Bustos virus. Gene expression analysis of the Bustos virus revealed that infected cells contain viral subgenomic RNAs that probably include open reading frame (ORF) 2 or ORF3. Purified Bustos virus particles contained at least three proteins, and the major component (a probable major capsid protein) is encoded by ORF3. Bustos virus did not show infectivity in mammalian BHK-21 cells, suggesting that it is an insect-specific virus, like other known negeviruses. PMID- 27671779 TI - Cryo-Electron Tomography: Can it Reveal the Molecular Sociology of Cells in Atomic Detail? AB - Traditionally, macromolecular structure determination is performed ex situ, that is, with purified materials. But, there are strong incentives to develop approaches to study them in situ in their native functional context. In recent years, cryo-electron tomography (cryo-ET) has emerged as a powerful method for visualizing the molecular organization of unperturbed cellular landscapes with the potential to attain near-atomic resolution. Here, we review recent work on several macromolecular assemblies, demonstrating the power of in situ studies. We also highlight technical challenges and discuss ways to meet them. PMID- 27671778 TI - Corticosteroids in IgA Nephropathy: Lessons from Recent Studies. AB - IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to ESRD. The immune and autoimmune responses that characterize IgAN indicate a potential benefit for corticosteroids. The 2012 Kidney Disease Improving Global Outcome (KDIGO) guidelines suggest giving corticosteroids to patients with rather preserved renal function (GFR>50 ml/min per 1.73 m2) and persistent proteinuria >1 g/d, despite 3-6 months of optimized supportive care with renin-angiotensin system blockers. However, the evidence supporting this guideline was considered of low quality. More recent results from large cohort studies and randomized, controlled trials have provided conflicting messages about the benefits of corticosteroid treatment over supportive care alone, mostly involving optimized renin-angiotensin system blockade, which might generate further uncertainty in the therapeutic choice. Overall, these results indicate that corticosteroids are a powerful tool for treating patients with IgAN; however, treatment success is not universal and mostly occurs in patients who are highly proteinuric with early CKD. In patients with advanced CKD, the side effects of corticosteroids increase, and the renal protection decreases. This brief review aimed at integrating the findings of these recently published reports to provide balanced advice for clinicians as well as suggestions for future trials. PMID- 27671780 TI - Tracking Multiple Statistics: Simultaneous Learning of Object Names and Categories in English and Mandarin Speakers. AB - Two experiments were conducted to examine adult learners' ability to extract multiple statistics in simultaneously presented visual and auditory input. Experiment 1 used a cross-situational learning paradigm to test whether English speakers were able to use co-occurrences to learn word-to-object mappings and concurrently form object categories based on the commonalities across training stimuli. Experiment 2 replicated the first experiment and further examined whether speakers of Mandarin, a language in which final syllables of object names are more predictive of category membership than English, were able to learn words and form object categories when trained with the same type of structures. The results indicate that both groups of learners successfully extracted multiple levels of co-occurrence and used them to learn words and object categories simultaneously. However, marked individual differences in performance were also found, suggesting possible interference and competition in processing the two concurrent streams of regularities. PMID- 27671781 TI - Online Partner Seeking and Sexual Risk Among HIV+ Gay and Bisexual Men: A Dialectical Perspective. AB - For almost two decades, researchers have explored the relationship between online partner seeking (OPS) and HIV/STI transmission risk behavior among men who have sex with men (MSM), including gay- and bisexual-identified men. A dichotomy has emerged with some findings that OPS is associated with greater sexual risk behavior, and a sparser but emerging literature that men may use OPS for sexual risk reduction. This study examined the association between proportion of partners met online and sexual risk behavior in a sample of 170 HIV-positive gay- and bisexual-identified men. Participants completed assessments including psychosocial factors and a comprehensive assessment of sexual behavior, including total number of male partners, and condomless insertive and receptive anal sex with HIV-negative/unknown serostatus partners or HIV-positive male partners. Our findings support taking a dialectical stance and indicate that OPS may impact risk differently given different individual and contextual circumstances. PMID- 27671782 TI - The Development of In Vivo Measures to Assess the Impact of Sex-Drive Reducing Medications in an Offender with an Intellectual Disability. AB - The ability to adequately evaluate medications in the treatment of paraphilias has been limited by reliance upon self-report as a measure of effectiveness over periods of time that may be too short to detect reoffending. One solution to this shortcoming is the development of valid, long-term, stable assessment measures. The purpose of this case study was to analyze the effects of Prozac and Provera on an array of behaviors germane to the successful treatment of paraphilias, including: (a) sexual arousal in the laboratory and natural environment, (b) sexual thoughts (deviant and nondeviant) accompanied by arousal in the natural environment, and (c) overt actions in the community associated with increased risk of reoffending over a 31-month period for an exhibitionist with an intellectual disability. Despite the ineffectiveness of the medications, the measures demonstrated long-term, differentiated significant clinical responding; further underscored the importance of assessing deviant sexual arousal and adherence to relapse-prevention procedures in the natural environment; and provided a new methodology to assess sexual preoccupations and sexual arousal. Use of these in vivo measures raises questions regarding their potential to improve the predictability of risk assessments, and serve as an aide in the analysis of whether a treatment procedure is effective for an individual. PMID- 27671783 TI - Differences Between Landline and Mobile Phone Users in Sexual Behavior Research. AB - This study investigated differences between the demographic characteristics, participation rates (i.e., agreeing to respond to questions about sexual behavior), and sexual behaviors of landline and mobile phone samples in Australia. A nationally representative sample of Australians aged 18 years and over was recruited via random digit dialing in December 2011 to collect data via computer-assisted telephone interviews. A total of 1012 people (370 men, 642 women) completed a landline interview and 1002 (524 men, 478 women) completed a mobile phone interview. Results revealed that telephone user status was significantly related to all demographic variables: gender, age, educational attainment, area of residence, country of birth, household composition, and current ongoing relationship status. In unadjusted analyses, telephone status was also associated with women's participation rates, participants' number of other sex sexual partners in the previous year, and women's lifetime sexual experience. However, after controlling for significant demographic factors, telephone status was only independently related to women's participation rates. Post hoc analyses showed that significant, between-group differences for all other sexual behavior outcomes could be explained by demographic covariates. Results also suggested that telephone status may be associated with participation bias in research on sexual behavior. Taken together, these findings highlight the importance of sampling both landline and mobile phone users to improve the representativeness of sexual behavior data collected via telephone interviews. PMID- 27671784 TI - Men's and Women's Use and Creation of Online Sexually Explicit Materials Including Fandom-Related Works. AB - The Internet and mobile computing have been highly influential in shaping the modern technological era and subsequently the production of and access to online sexually explicit materials (SEM). Fandom-the realm of fans sharing a common interest-has also adapted to the Internet, which has changed how fans access and distribute fanworks (i.e., material created by fans such as stories and art), many of which contain SEM. The current study examined gender differences in the use and creation of online SEM by surveying 468 men and 347 women (ages 18 or older; mean age = 33.8 years) residing in North America. Participants completed anonymous measures assessing demographic information, experiences using and creating online SEM, and measures of related sexual attitudes. Use of online SEM was widely reported by participants, with men (87.8 %) indicating more use than with women (67.4 %). As expected, few participants reported creating online SEM (3.6 % of men, 4.9 % of women). Men and women reported similar levels of preferred sexual explicitness in the online SEM that they used. There were no significant gender differences in the use of fanworks reported by men (14.3 %) and women (14.7 %) or in the creation of fanworks (1.5 % of men, 3.2 % of women). Fandom-related online SEM use was predicted only by more permissive sexual attitudes (one of eight predictors). Although there were many similarities between men's and women's use of online SEM, some gender differences were found in their motives for online SEM use. Findings are discussed in terms of the context in which men and women experience online SEM. PMID- 27671786 TI - Participation restriction in childhood phenotype of myotonic dystrophy type 1: a systematic retrospective chart review. AB - AIM: Myotonic dystrophy type 1 (DM1), a neuromuscular disorder, is divided into four clinical phenotypes: congenital; childhood; adult-onset, and late-onset. Publications about the childhood phenotype, especially the long-term outcome, are scarce. The aims of this study were to assess and describe participation outcomes in adults with the childhood phenotype. METHOD: A retrospective chart methodology. Data were extracted from health records for 63 adults with childhood DM1 (32 males, 31 females; mean age 34y, standard deviation [SD] 11y 6mo; range 18-54y) who had attended the Saguenay Neuromuscular Clinic, Canada. RESULTS: Thirty-four adults (54%) lived with their parents or in foster homes, and most patients needed services or help to live independently. A significant proportion (22%) were isolated in regard to friendship. Very few adults had children, although 33% lived with a spouse. The majority of patients (86%) relied on social security and only one person was currently working. Financial responsibilities were often an issue and 13 (21%) were under legal guardianship. INTERPRETATION: This study showed that patients with the childhood phenotype present a guarded prognosis regarding long-term social participation. These participation restrictions could be related to behavioural, cognitive, and social stigma problems in childhood. This study illustrates the absolute necessity to pursue an interdisciplinary follow-up of these patients when they are reaching adulthood. PMID- 27671785 TI - Whole genome sequencing of a rare rotavirus from archived stool sample demonstrates independent zoonotic origin of human G8P[14] strains in Hungary. AB - Genotype P[14] rotaviruses in humans are thought to be zoonotic strains originating from bovine or ovine host species. Over the past 30 years only few genotype P[14] strains were identified in Hungary totaling<0.1% of all human rotaviruses whose genotype had been determined. In this study we report the genome sequence and phylogenetic analysis of a human genotype G8P[14] strain, RVA/Human-wt/HUN/182-02/2001/G8P[14]. The whole genome constellation (G8-P[14]-I2 R2-C2-M2-A11-N2-T6-E2-H3) of this strain was shared with another Hungarian zoonotic G8P[14] strain, RVA/Human-wt/HUN/BP1062/2004/G8P[14], although phylogenetic analyses revealed the two rotaviruses likely had different progenitors. Overall, our findings indicate that human G8P[14] rotavirus detected in Hungary in the past originated from independent zoonotic events. Further studies are needed to assess the public health risk associated with infections by various animal rotavirus strains. PMID- 27671787 TI - Bullying in surgery isn't just Australia's problem. PMID- 27671788 TI - In Focus in HCB. PMID- 27671789 TI - Proteomics analysis of the endogenous, constitutive, leaf SUMOylome. AB - : SUMOylation is a post-translational modification which regulates a number of critical biological processes in, for example mammals, yeast and plants. In order to fully understand the functional effects of SUMOylation an essential first step is the identification of endogenous targets for SUMOylation. Here we report the results of using a recently developed proteomic approach based on the use of 3D gels to identify the endogenous SUMO targets in leaves of Solanum tuberosum. By using 3D gels we avoid the problem of co-migration of proteins, which is a major limitation of 2D gels, and we enable the use of the highly sensitive CyDye DIGE fluor saturation dyes. Using this new method we have identified 39 individual proteins as probable SUMO targets in leaves of Solanum tuberosum. The advantages of this method compared with other approaches are discussed, and possible future developments are outlined. SIGNIFICANCE: The authors have no conflicts of interest to declare. All authors have approved the manuscript and agree with submission to Journal of Proteomics. PMID- 27671790 TI - The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis. AB - Nonobese diabetic (NOD) mice are a model for type 1 diabetes that displays defects in central immune tolerance, including impairment of thymocyte apoptosis and proliferation. Thymocyte apoptosis is decreased in NOD/Lt mice compared to nondiabetic C3H/HeJ and C57BL/6 mice. Analysis of a set of NOD.C3H and NOD.B6 congenic mouse strains for distal chromosome 6 localizes the phenotype to the 700 kb Idd6.3 interval. Idd6.3 contains the type 1 diabetes candidate gene aryl hydrocarbon receptor nuclear translocator-like 2 (Arntl2), encoding a circadian rhythm-related transcription factor. Newly generated Arntl2 -/- mouse strains reveal that inactivation of the B6 allele of Arntl2 is sufficient to both decrease thymocyte apoptosis and proliferation. When expressed from C3H or B6 alleles, ARNTL2 inhibits the transcription of interleukin 21 (Il21), a major player in the regulation of immune responses. IL-21 injection abolishes the B6 allele-mediated decrease of apoptosis and proliferation. Interestingly, IL-21 also leads to an increase in thymic proinflammatory Th17 helper cells. Our results identify Arntl2 as a gene controlling thymocyte apoptosis and proliferation along with Th17 development through the IL-21 pathway. PMID- 27671792 TI - A test of basic psychological needs theory in young soccer players: time-lagged design at the individual and team levels. AB - Within the framework of basic psychological needs theory (Deci & Ryan, 2000), multilevel structural equation modeling (MSEM) with a time-lagged design was used to test a mediation model examining the relationship between perceptions of coaches' interpersonal styles (autonomy supportive and controlling), athletes' basic psychological needs (satisfaction and thwarting), and indicators of well being (subjective vitality) and ill-being (burnout), estimating separately between and within effects. The participants were 597 Spanish male soccer players aged between 11 and 14 years (M = 12.57, SD = 0.54) from 40 teams who completed a questionnaire package at two time points in a competitive season. Results revealed that at the individual level, athletes' perceptions of autonomy support positively predicted athletes' need satisfaction (autonomy, competence, and relatedness), whereas athletes' perceptions of controlling style positively predicted athletes' need thwarting (autonomy, competence, and relatedness). In turn, all three athletes' need satisfaction dimensions predicted athletes' subjective vitality and burnout (positively and negatively, respectively), whereas competence thwarting negatively predicted subjective vitality and competence and relatedness positively predicted burnout. At the team level, team perceptions of autonomy supportive style positively predicted team autonomy and relatedness satisfaction. Mediation effects only appeared at the individual level. PMID- 27671793 TI - Incidence and molecular characterisation of lumpy skin disease virus in Zimbabwe using the P32 gene. AB - Between January, 2013 and December, 2014, there was a lumpy skin disease (LSD) outbreak that affected cattle in different localities of Zimbabwe. The outbreak resulted in severe economic losses to the livestock industry. A retrospective study was conducted by examining stored veterinary records of the LSD outbreak at the Central Veterinary Laboratory (CVL) in Harare, Zimbabwe. Over the 2-year period, a total of 10,038 cases and 880 deaths (8.77 %) were recorded. LSD was reported from all regions of the country, with the highest incidence occurring in Mashonaland West (30.95 %) and Midlands province (14.59 %). The frequency of reported outbreaks was highest in March and April, with the lowest reported cases occurring in November. A total of 25 representative specimens (skin biopsies) were collected from nodular skin lesions of infected cattle, and after viral DNA isolation, the P32 gene was successfully amplified, by using PCR, in 88 % (22/25) of all assayed specimens. Out of the 22 samples that showed amplification, 16 (73 %) were selected for DNA sequencing, and from these, 13 sequences were submitted to GenBank and assigned accession numbers: KX033494, KX033495, KX033496, KX033497, KXO33498, KX033499, KX033500, KX033501, KX033502, KX033503, KX033504, KX033505 and KX033506. Phylogenetic analyses of the 13 sequences was done by using MEGA 7 and showed that the viruses formed two major clusters implying that at least two strains of LSDV are in circulation in Zimbabwe. This study provides the first report on the incidence and molecular characterisation of LSDV in Zimbabwe. PMID- 27671791 TI - Viable Ednra Y129F mice feature human mandibulofacial dysostosis with alopecia (MFDA) syndrome due to the homologue mutation. AB - Animal models resembling human mutations are valuable tools to research the features of complex human craniofacial syndromes. This is the first report on a viable dominant mouse model carrying a non-synonymous sequence variation within the endothelin receptor type A gene (Ednra c.386A>T, p.Tyr129Phe) derived by an ENU mutagenesis program. The identical amino acid substitution was reported recently as disease causing in three individuals with the mandibulofacial dysostosis with alopecia (MFDA, OMIM 616367) syndrome. We performed standardized phenotyping of wild-type, heterozygous, and homozygous Ednra Y129F mice within the German Mouse Clinic. Mutant mice mimic the craniofacial phenotypes of jaw dysplasia, micrognathia, dysplastic temporomandibular joints, auricular dysmorphism, and missing of the squamosal zygomatic process as described for MFDA affected individuals. As observed in MFDA-affected individuals, mutant Ednra Y129F mice exhibit hearing impairment in line with strong abnormalities of the ossicles and further, reduction of some lung volumetric parameters. In general, heterozygous and homozygous mice demonstrated inter-individual diversity of expression of the craniofacial phenotypes as observed in MFDA patients but without showing any cleft palates, eyelid defects, or alopecia. Mutant Ednra Y129F mice represent a valuable viable model for complex human syndromes of the first and second pharyngeal arches and for further studies and analysis of impaired endothelin 1 (EDN1)-endothelin receptor type A (EDNRA) signaling. Above all, Ednra Y129F mice model the recently published human MFDA syndrome and may be helpful for further disease understanding and development of therapeutic interventions. PMID- 27671794 TI - SYNE1 mutations cause autosomal-recessive ataxia with retained reflexes in Brazilian patients. PMID- 27671795 TI - Fabrication of potato-like silver molybdate microstructures for photocatalytic degradation of chronic toxicity ciprofloxacin and highly selective electrochemical detection of H2O2. AB - In the present work, potato-like silver molybdate (Ag2MoO4) microstructures were synthesized through a simple hydrothermal method. The microstructures of Ag2MoO4 were characterized by various analytical and spectroscopic techniques such as XRD, FTIR, Raman, SEM, EDX and XPS. Interestingly, the as-prepared Ag2MoO4 showed excellent photocatalytic and electrocatalytic activity for the degradation of ciprofloxacin (CIP) and electrochemical detection of hydrogen peroxide (H2O2), respectively. The ultraviolet-visible (UV-Vis) spectroscopy results revealed that the potato-like Ag2MoO4 microstructures could offer a high photocatalytic activity towards the degradation of CIP under UV-light illumination, leads to rapid degradation within 40 min with a degradation rate of above 98%. In addition, the cyclic voltammetry (CV) and amperometry studies were realized that the electrochemical performance of Ag2MoO4 modified electrode toward H2O2 detection. Our H2O2 sensor shows a wide linear range and lower detection limit of 0.04-240 MUM and 0.03 MUM, respectively. The Ag2MoO4 modified electrode exhibits a high selectivity towards the detection of H2O2 in the presence of different biological interferences. These results suggested that the development of potato like Ag2MoO4 microstructure could be an efficient photocatalyst as well as electrocatalyst in the potential application of environmental, biomedical and pharmaceutical samples. PMID- 27671796 TI - Inhibitory Effects of Multiple-Dose Treatment with Baicalein on the Pharmacokinetics of Ciprofloxacin in Rats. AB - Ciprofloxacin is used as a treatment for urinary and respiratory tract infections in clinical practice. Baicalein, a major flavonoid present in Scutellaria baicalensis, is a well-known and potent antibacterial compound used in complementary and alternative medicine practices. The present study aimed to clarify the effects of multiple-dose treatment with baicalein on the pharmacokinetics of ciprofloxacin in rats. Following the oral administration of baicalein (20, 40, or 80 mg/kg) for five consecutive days, the rats received an oral administration of ciprofloxacin (20 mg/kg). Blood samples were collected at specific time points, and the plasma concentrations of ciprofloxacin were determined by using high-performance liquid chromatography. To evaluate the mechanisms underlying the interaction between baicalein and ciprofloxacin, a rhodamine 123 accumulation assay was performed in LS-180 cells. A pharmacokinetic study revealed that multiple-dose treatment with baicalein significantly decreased the peak serum concentration (Cmax ), area under the curve (AUC0 -> 480 min ), and relative bioavailability (Frel ) of ciprofloxacin (p < 0.05). The rhodamine 123 accumulation assay revealed that treatment with baicalein for 48 h markedly reduced the intracellular accumulation of rhodamine 123. Taken together, these findings suggest that baicalein may result in the therapeutic failure of ciprofloxacin or other quinolone-based antibiotics used for chemotherapy in clinical practice. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27671797 TI - Perforator-based propeller flaps reliability in upper extremity soft tissue reconstruction: a systematic review. AB - : Current data on upper extremity propeller flaps are poor and do not allow the assessment of the safety of this technique. A systematic literature review was conducted searching PubMed, EMBASE, and the Cochrane Library electronic databases, and the selection process was adapted from the preferred reporting items for systematic reviews and meta-analysis statement. The final analysis included ten relevant articles involving 117 flaps. The majority of flaps were used for the hand, distal wrist, and elbow. The radial artery perforator and ulnar artery perforator were the most frequently used flaps. The were 7% flaps with venous congestion and 3% with complete necrosis. No difference in complications rate was found for different flaps sites. Perforator-based propeller flaps appear to be an interesting procedure for covering soft tissue defects involving the upper extremities, even for large defects, but the procedure requires experience and close monitoring. LEVEL OF EVIDENCE: II. PMID- 27671798 TI - Comparing radial styloid size between osteoarthritic and healthy wrists: a pathoanatomical three-dimensional study. AB - : Radial styloid pointing due to spur formation is considered an early sign of osteoarthritis, but is sometimes difficult to distinguish from normal anatomic variation. In this pathoanatomical study we used three-dimensional imaging techniques to evaluate quantitatively whether the styloid size is larger in wrists with scaphoid non-union than in healthy wrists. We compared these findings with duration of the non-union and with the scaphoid non-union advanced collapse classification, which was based on radiographic assessment of the general level of wrist osteoarthritis. In 31 patients, the injured styloid was consistently larger than the contralateral healthy styloid. In 74% of the patients this pathoanatomical difference (maximum 5 mm) exceeded anatomical left-to-right variation in styloid size (maximum 2 mm), indicating significant pointing. Increased styloid pointing was associated with older non-unions, and with more severe osteoarthritis. Three-dimensional styloid pointing analysis is an objective method to assess osteoarthritic progression. Combining traditional qualitative evaluation and quantitative measurements may improve the classification of wrist osteoarthritis. LEVEL OF EVIDENCE: IV. PMID- 27671799 TI - Review of Recent Advances in Peripheral Nerve Stimulation (PNS). AB - Peripheral nerve stimulation (PNS) for the treatment of chronic pain has become an increasingly important field in the arena of neuromodulation, given the ongoing advances in electrical neuromodulation technology since 1999 permitting minimally invasive approaches using an percutaneous approach as opposed to implantable systems. Our review aims to provide clinicians with the recent advances and studies in the field, with specific emphasis on clinical data and indications that have been accumulated over the last several years. In addition, we aim to address key basic science studies to further emphasize the importance of translational research outcomes driving clinical management. PMID- 27671800 TI - Late diagnosis of post-traumatic ruptured pericardium with cardiac herniation. PMID- 27671801 TI - Physical Activity, Screen-Time Behavior, and Obesity Among 13-Year Olds in Ireland with and without Autism Spectrum Disorder. AB - The primary purposes of this study were to compare (a) physical activity participation, screen-time habits, obesity, and (b) reported reasons for lack of participation in sport, between a nationally representative sample of Irish children with and without autism spectrum disorder (ASD). Participation in moderate to vigorous activity, light activity, and sports was significantly lower among the group with ASD. On examination of screen time variables, no significant differences were seen between groups. However, time spent watching TV was higher among children with ASD. Overweight or obese status was more prevalent among the group with ASD (34.4 vs. 24.7 %). The findings are discussed in relation to international statistics on youth physical activity, screen-time, and weight status, and recommendations are provided for future research. PMID- 27671805 TI - Current Research Outcomes From the Spinal Cord Injury Model Systems. PMID- 27671803 TI - Magnetic resonance imaging of infarct-induced canonical wingless/integrated (Wnt)/beta-catenin/T-cell factor pathway activation, in vivo. AB - AIMS: Combined magnetic resonance imaging (MRI) of molecular and morpho functional changes might prove highly valuable for the elucidation of pathological processes involved in the development of cardiac diseases. Our aim was to test a novel MRI reporter gene for in vivo assessment of the canonical Wnt/beta-catenin/TCF pathway activation, an important regulator of post-ischaemic cardiac remodelling. METHODS AND RESULTS: We designed and developed a chimeric construct encoding for both of iron-binding human ferritin heavy chain (hFTH) controlled by the beta-catenin-responsive TCF/lymphoid-enhancer binding factor (Lef) promoter and constitutively expressed green fluorescent protein (GFP). It was carried by adeno-associated virus serotype 9 (rAAV9) vectors and delivered to the peri-infarct myocardium of rats subjected to coronary ligation (n = 11). By 1.5 T MRI and a multiecho T2* gradient echo sequence, we detected iron accumulation only in the border zone of the transduced infarcted hearts. In the same cardiac area, post-mortem histological analysis confirmed the co-existence of iron accumulation and GFP. The iron signal was absent when rats (n = 6) were chronically treated with SEN195 (10 mg/kg/day), a small-molecular inhibitor of beta-catenin/TCF-dependent gene transcription. Canonical Wnt pathway inhibition attenuated the post-ischaemic remodelling process, as demonstrated by the significant preservation of cardiac function, the 42 +/- 1% increase of peri infarct arteriolar density and 43 +/- 3% reduction in infarct scar size compared with untreated animals. CONCLUSIONS: The TCF/Lef promoter-hFTH construct is a novel and reliable MRI reporter gene for in vivo detection of the canonical Wnt/beta-catenin/TCF activation state in response to cardiac injury and therapeutic interventions. PMID- 27671806 TI - Spinal Cord Injury Model Systems: Review of Program and National Database From 1970 to 2015. AB - The Spinal Cord Injury Model Systems (SCIMS) centers have provided continuous, comprehensive multidisciplinary care for persons with spinal cord injury (SCI) in the United States since their inception in 1970. In addition, the research conducted and the analysis of data collected at these centers facilitate advances in the care and the overall quality of life for people with SCI. Over the past 45 years, the SCIMS program and National Spinal Cord Injury Database (NSCID) have undergone major revisions, which must be recognized in the planning, conduct, and interpretation of SCIMS research to prevent misinterpretation of findings. Therefore, we provide herein a brief review of the SCIMS program and the associated NSCID throughout its history, emphasizing changes and accomplishments within the past 15 years, to facilitate a better understanding and interpretation of the data presented in SCIMS research publications, including the articles published in this special issue of the Archives. PMID- 27671804 TI - Runx2 deletion in smooth muscle cells inhibits vascular osteochondrogenesis and calcification but not atherosclerotic lesion formation. AB - Aims: Vascular smooth muscle cells (SMCs) are major precursors contributing to osteochondrogenesis and calcification in atherosclerosis. Runt-related transcription factor-2 (Runx2) has been found essential for SMC differentiation to an osteochondrogenic phenotype and subsequent calcification in vitro. A recent study using a conditional targeting allele that produced a truncated Runx2 protein in SMCs of ApoE-/- mice showed reduced vascular calcification, likely occurring via reduction of receptor activator of nuclear factor-kappaB ligand (RANKL), macrophage infiltration, and atherosclerotic lesion formation. Using an improved conditional Runx2 knockout mouse model, we have elucidated new roles for SMC-specific Runx2 in arterial intimal calcification (AIC) without effects on atherosclerotic lesion size. Methods and results: We used an improved targeting construct to generate LDLr-/- mice with floxed-Runx2 alleles ( LDLr-/- :Runx2 f/f ) such that Cre-mediated recombination ( LDLr-/- :Runx2 DeltaSM ) does not produce functional truncated Runx2 protein, thereby avoiding off-target effects. We found that both LDLr-/- :Runx2 f/f and LDLr-/- :Runx2 DeltaSM mice fed with a high fat diet developed atherosclerosis. SMC-specific Runx2 deletion did not significantly reduce atherosclerotic lesion size, macrophage number, or expression of RANKL, MCP-1, and CCR2. However, it significantly reduced AIC by 50%. Mechanistically, Sox9 and type II collagen were unaltered in vessels of LDLr /- :Runx2 DeltaSM mice compared to LDLr-/- :Runx2 f/f counterparts, while type X collagen, MMP13 and the osteoblastic marker osteocalcin were significantly reduced. Conclusions: SMC autonomous Runx2 is required for SMC differentiation towards osteoblast-like cells, SMC-derived chondrocyte maturation and AIC in atherosclerotic mice. These effects were independent of systemic lipid metabolism, RANKL expression, macrophage infiltration, and atheromatous lesion progression. PMID- 27671807 TI - [Cutaneous melanocytic tumors. Case 6]. PMID- 27671802 TI - Endothelial repair in stented arteries is accelerated by inhibition of Rho associated protein kinase. AB - AIMS: Stent deployment causes endothelial cells (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow perturbation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration, we identified an intervention that promotes endothelial repair in stented arteries. METHODS AND RESULTS: In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel plate flow chamber with 100 MUm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (P < 0.01). To more closely mimic the in vivo situation, we cultured EC on the inner surface of polydimethylsiloxane tubing containing Coroflex Blue stents (65 MUm struts) and monitored migration. ROCK inhibition significantly enhanced EC accumulation downstream from struts under flow (P < 0.05). We investigated the effects of ROCK inhibition on re endothelialization in vivo using a porcine model of EC denudation and stent placement. En face staining and confocal microscopy revealed that inhibition of ROCK using fasudil (30 mg/day via osmotic minipump) significantly increased re endothelialization of stented carotid arteries (P < 0.05). CONCLUSIONS: Stent struts delay endothelial repair by generating localized bidirectional flow which traps migrating EC. ROCK inhibitors accelerate endothelial repair of stented arteries by enhancing EC polarity and migration through regions of bidirectional flow. PMID- 27671808 TI - [Cutaneous melanocytic tumors. Pre-test answers]. PMID- 27671809 TI - Groundwater shapes sediment biogeochemistry and microbial diversity in a submerged Great Lake sinkhole. AB - For a large part of earth's history, cyanobacterial mats thrived in low-oxygen conditions, yet our understanding of their ecological functioning is limited. Extant cyanobacterial mats provide windows into the putative functioning of ancient ecosystems, and they continue to mediate biogeochemical transformations and nutrient transport across the sediment-water interface in modern ecosystems. The structure and function of benthic mats are shaped by biogeochemical processes in underlying sediments. A modern cyanobacterial mat system in a submerged sinkhole of Lake Huron (LH) provides a unique opportunity to explore such sediment-mat interactions. In the Middle Island Sinkhole (MIS), seeping groundwater establishes a low-oxygen, sulfidic environment in which a microbial mat dominated by Phormidium and Planktothrix that is capable of both anoxygenic and oxygenic photosynthesis, as well as chemosynthesis, thrives. We explored the coupled microbial community composition and biogeochemical functioning of organic rich, sulfidic sediments underlying the surface mat. Microbial communities were diverse and vertically stratified to 12 cm sediment depth. In contrast to previous studies, which used low-throughput or shotgun metagenomic approaches, our high-throughput 16S rRNA gene sequencing approach revealed extensive diversity. This diversity was present within microbial groups, including putative sulfate-reducing taxa of Deltaproteobacteria, some of which exhibited differential abundance patterns in the mats and with depth in the underlying sediments. The biological and geochemical conditions in the MIS were distinctly different from those in typical LH sediments of comparable depth. We found evidence for active cycling of sulfur, methane, and nutrients leading to high concentrations of sulfide, ammonium, and phosphorus in sediments underlying cyanobacterial mats. Indicators of nutrient availability were significantly related to MIS microbial community composition, while LH communities were also shaped by indicators of subsurface groundwater influence. These results show that interactions between the mats and sediments are crucial for sustaining this hot spot of biological diversity and biogeochemical cycling. PMID- 27671811 TI - Berberine and Its Role in Chronic Disease. AB - Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense [2] (Amur corktree), Coptis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana (prickly poppy) and Eschscholzia californica (Californian poppy). In vitro it exerts significant anti inflammatory and antioxidant activities. In animal models berberine has neuroprotective and cardiovascular protective effects. In humans, its lipid lowering and insulin-resistance improving actions have clearly been demonstrated in numerous randomized clinical trials. Moreover, preliminary clinical evidence suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases. Altogether the available evidences suggest a possible application of berberine use in the management of chronic cardiometabolic disorders. PMID- 27671810 TI - Curcumin and Its Role in Chronic Diseases. AB - Curcumin, a yellow pigment from the spice turmeric, is used in Indian and Chinese medicine since ancient times for wide range of diseases. Extensive scientific research on this molecule performed over the last 3 to 4 decades has proved its potential as an important pharmacological agent. The antioxidant, anti inflammatory, antimicrobial and chemopreventive activities of curcumin have been extended to explore this molecule against many chronic diseases with promising results. Further, its multitargeting ability and nontoxic nature to humans even up to 12 g/day have attracted scientists to explore this as an anticancer agent in the clinic, which is in different phases of trials. With much more scope to be investigated and understood, curcumin becomes one of the very few inexpensive botanical molecules with potent therapeutic abilities. PMID- 27671812 TI - Emodin and Its Role in Chronic Diseases. AB - Diseases, such as heart disease, stroke, cancer, respiratory diseases, and diabetes, are by far the leading cause of mortality in the world, representing 60 % of all deaths. Although substantial medical advances have been made and many therapeutic approaches proposed yet traditional medicine and medicinal plants find an important place in therapy. They have been providing invaluable solutions to the various health problems. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural anthraquinone derivative found in various Chinese medicinal herbs. Traditionally, it has been used as an active constituent of many herbal laxatives. However, in the last few years, significant progress has been made in studying the biological effects of emodin at cellular and molecular levels and it is emerging as an important therapeutic agent. This review provides an overview of the modulatory effects of emodin in various diseases and cell signaling pathways, which may have important implications in its future clinical use. PMID- 27671813 TI - Ursolic Acid and Chronic Disease: An Overview of UA's Effects On Prevention and Treatment of Obesity and Cancer. AB - Chronic diseases pose a worldwide problem and are only continuing to increase in incidence. Two major factors contributing to the increased incidence in chronic disease are a lack of physical activity and poor diet. As the link between diet and lifestyle and the increased incidence of chronic disease has been well established in the literature, novel preventive, and therapeutic methods should be aimed at naturally derived compounds such as ursolic acid (UA), the focus of this chapter. As chronic diseases, obesity and cancer share the common thread of inflammation and dysregulation of many related pathways, the focus here will be on these two chronic diseases. Significant evidence in the literature supports an important role for natural compounds such as UA in the prevention and treatment of chronic diseases like obesity and cancer, and here we have highlighted many of the ways UA has been shown to be a beneficial and versatile phytochemical. PMID- 27671814 TI - Tocotrienol and Its Role in Chronic Diseases. AB - Tocotrienol is a member of vitamin E family and is well-known for its antioxidant and anti-inflammatory properties. It is also a suppressor of mevalonate pathway responsible for cholesterol and prenylated protein synthesis. This review aimed to discuss the health beneficial effects of tocotrienol, specifically in preventing or treating hyperlipidaemia, diabetes mellitus, osteoporosis and cancer with respect to these properties. Evidence from in vitro, in vivo and human studies has been examined. It is revealed that tocotrienol shows promising effects in preventing or treating the health conditions previously mentioned in in vivo and in vitro models. In some cases, alpha-tocopherol attenuates the biological activity of tocotrienol. Except for its cholesterol-lowering effects, data on the health-promoting effects of tocotrienol in human are limited. As a conclusion, the encouraging results on the health beneficial effects of tocotrienol should motivate researchers to explore its potential use in human. PMID- 27671815 TI - Indole-3-Carbinol and Its Role in Chronic Diseases. AB - Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3'-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well recognized chemoprevention potential. Initially, these compounds were classified as blocking agents that increase drug-metabolizing enzyme activity. Now it is widely accepted that I3C and DIM affect multiple signaling pathways and target molecules controlling cell division, apoptosis, or angiogenesis deregulated in cancer cells. Although most of the current data support the role of I3C and DIM in prevention of hormone-dependent cancers, it seems that their application in prevention of the other cancer as well as cardiovascular disease, obesity, and diabetes reduction is also possible. This chapter summarizes the current experimental data on the I3C and DIM activity and the results of clinical studies indicating their role in prevention of chronic diseases. PMID- 27671816 TI - Sanguinarine and Its Role in Chronic Diseases. AB - The use of natural products derived from plants as medicines precedes even the recorded human history. In the past few years there were renewed interests in developing natural compounds and understanding their target specificity for drug development for many devastating human diseases. This has been possible due to remarkable advancements in the development of sensitive chemistry and biology tools. Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of the plant species Sanguinaria canadensis. The alkaloid can exist in the cationic iminium and neutral alkanolamine forms. Sanguinarine is an excellent DNA and RNA intercalator where only the iminium ion binds. Both forms of the alkaloid, however, shows binding to functional proteins like serum albumins, lysozyme and hemoglobin. The molecule is endowed with remarkable biological activities and large number of studies on its various activities has been published potentiating its development as a therapeutic agent particularly for chronic human diseases like cancer, asthma, etc. In this article, we review the properties of this natural alkaloid, and its diverse medicinal applications in relation to how it modulates cell death signaling pathways and induce apoptosis through different ways, its utility as a therapeutic agent for chronic diseases and its biological effects in animal and human models. These data may be useful to understand the therapeutic potential of this important and highly abundant alkaloid that may aid in the development of sanguinarine-based therapeutic agents with high efficacy and specificity. PMID- 27671817 TI - Piperine and Its Role in Chronic Diseases. AB - Alkaloids include a family of naturally occurring chemical compounds containing mostly basic nitrogen atoms. Piperine is an alkaloid present in black pepper (Piper nigrum), one of the most widely used spices, in long pepper (Piper longum), and other Piper species fruits belonging to the family of Piperaceae. Piperine is responsible for the black pepper distinct biting quality. Piperine has many pharmacological effects and several health benefits, especially against chronic diseases, such as reduction of insulin-resistance, anti-inflammatory effects, and improvement of hepatic steatosis. The aim of this chapter is to summarize the effects of piperine, alone or in combination with other drugs and phytochemicals, in chronic diseases. PMID- 27671818 TI - Therapeutic Potential and Molecular Targets of Piceatannol in Chronic Diseases. AB - Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene; PIC) is a naturally occurring stilbene present in diverse plant sources. PIC is a hydroxylated analog of resveratrol and produced from resveratrol by microsomal cytochrome P450 1A11/2 and 1B1 activities. Like resveratrol, PIC has a broad spectrum of health beneficial effects, many of which are attributable to its antioxidative and anti inflammatory activities. PIC exerts anticarcinogenic effects by targeting specific proteins involved in regulating cancer cell proliferation, survival/death, invasion, metastasis, angiogenesis, etc. in tumor microenvironment. PIC also has other health promoting and disease preventing functions, such as anti-obese, antidiabetic, neuroptotective, cardioprotective, anti-allergic, anti-aging properties. This review outlines the principal biological activities of PIC and underlying mechanisms with special focus on intracellular signaling molecules/pathways involved. PMID- 27671819 TI - Fisetin and Its Role in Chronic Diseases. AB - Chronic inflammation is a prolonged and dysregulated immune response leading to a wide variety of physiological and pathological conditions such as neurological abnormalities, cardiovascular diseases, diabetes, obesity, pulmonary diseases, immunological diseases, cancers, and other life-threatening conditions. Therefore, inhibition of persistent inflammation will reduce the risk of inflammation-associated chronic diseases. Inflammation-related chronic diseases require chronic treatment without side effects. Use of traditional medicines and restricted diet has been utilized by mankind for ages to prevent or treat several chronic diseases. Bioactive dietary agents or "Nutraceuticals" present in several fruits, vegetables, legumes, cereals, fibers, and certain spices have shown potential to inhibit or reverse the inflammatory responses and several chronic diseases related to chronic inflammation. Due to safe, nontoxic, and preventive benefits, the use of nutraceuticals as dietary supplements or functional foods has increased in the Western world. Fisetin (3,3',4',7-tetrahydroxyflavone) is a dietary flavonoid found in various fruits (strawberries, apples, mangoes, persimmons, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine that has shown strong anti-inflammatory, anti-oxidant, anti tumorigenic, anti-invasive, anti-angiogenic, anti-diabetic, neuroprotective, and cardioprotective effects in cell culture and in animal models relevant to human diseases. In this chapter, we discuss the beneficial pharmacological effects of fisetin against different pathological conditions with special emphasis on diseases related to chronic inflammatory conditions. PMID- 27671820 TI - Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs. AB - Honokiol (C18H18O2) is a biphenolic natural product isolated from the bark and leaves of Magnolia plant spp. During the last decade or more, honokiol has been extensively studied for its beneficial effect against several diseases. Investigations have demonstrated that honokiol possesses anti-carcinogenic, anti inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity. Honokiol affects multiple signaling pathways, molecular and cellular targets including nuclear factor-kappaB (NF kappaB), STAT3, epidermal growth factor receptor (EGFR), cell survival signaling, cell cycle, cyclooxygenase and other inflammatory mediators, etc. Its chemopreventive and/or therapeutic effects have been tested against chronic diseases, such as cancers of different organs. In this chapter, we describe and discuss briefly the effect of honokiol against cancers of different organs, such as melanoma, non-melanoma, lung, prostate, breast, head and neck squamous cell carcinoma, urinary bladder cancer, gastric cancer, and neuroblastoma, etc. and describe its mechanism of action including various molecular and cellular targets. Although more rigorous in vivo studies are still needed, however it is expected that therapeutic effects and activities of honokiol may help in the development and designing of clinical trials against chronic diseases in human subjects. PMID- 27671821 TI - Celastrol and Its Role in Controlling Chronic Diseases. AB - Celastrol, a triterpenoid derived from traditional Chinese medicinal plants, has anti-inflammatory, antioxidant, and anticancer activities. Celastrol has shown preventive/therapeutic effects in experimental models of several chronic diseases. These include, chronic inflammatory and autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and psoriasis), neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis), atherosclerosis, obesity, Type 2 diabetes, and cancer. Celastrol modulates intricate cellular pathways and networks associated with disease pathology, and it interrupts or redirects the aberrant cellular and molecular events so as to limit disease progression and facilitate recovery, where feasible. The major cell signaling pathways modulated by celastrol include the NF-kB pathway, MAPK pathway, JAK/STAT pathway, PI3K/Akt/mTOR pathway, and antioxidant defense mechanisms. Furthermore, celastrol modulates cell proliferation, apoptosis, proteasome activity, heat-shock protein response, innate and adaptive immune responses, angiogenesis, and bone remodeling. Current understanding of the mechanisms of action of celastrol and information about its disease-modulating activities in experimental models have set the stage for testing celastrol in clinical studies as a therapeutic agent for several chronic human diseases. PMID- 27671822 TI - Boswellic Acids and Their Role in Chronic Inflammatory Diseases. AB - : Boswellic acids, which are pentacyclic triterpenes belong to the active pharmacological compounds of the oleogum resin of different Boswellia species. In the resin, more than 12 different boswellic acids have been identified but only KBA and AKBA received significant pharmacological interest. Biological Activity: In an extract of the resin of Boswellia species multiple factors are responsible for the final outcome of a therapeutic effect, be it synergistic or antagonistic. Moreover, the anti-inflammatory actions of BAs are caused by different mechanisms of action. They include inhibition of leukotriene synthesis and to a less extend prostaglandin synthesis. Furthermore inhibition of the complement system at the level of conversion of C3 into C3a and C3b. A major target of BAs is the immune system. Here, BEs as well as BAs including KBA and AKBA, have been shown to decrease production of proinflammatory cytokines including IL-1, IL-2, IL-6, IFN gamma and TNF-alpha which finally are directed to destroy tissues such as cartilage, insulin producing cells, bronchial, intestinal and other tissues. NFKB is considered to be the target of AKBA. The complex actions of BEs and BAs in inflamed areas may be completed by some effects that are localized behind the inflammatory process as such tissue destruction. In this case, in vitro- and animal studies have shown that BAs and BEs suppress proteolytic activity of cathepsin G, human leucocyte elastase, formation of oxygen radicals and lysosomal enzymes. PHARMACOKINETICS: Whereas KBA is absorbed reaching blood levels being close to in vitro IC50, AKBA which is more active in in vitro studies than KBA, but undergoes much less absorption than KBA. However, absorption of both is increased more than twice when taken together with a high-fat meal.Clinical Studies There are a variety of chronic inflammatory diseases which respond to treatment with extracts from the resin of Boswellia species. Though, the number of cases is small in related clinical studies, their results are convincing and supported by the preclinical data. These studies include rheumatoid arthritis, osteoarthritis, chronic colitis, ulcerative colitis, collagenous colitis, Crohn's disease and bronchial asthma. It can not be expected that there is cure from these diseases but at least improvement of symptoms in about 60-70 % of the cases. Side Effects The number and severity of side effects is extremely low. The most reported complaints are gastrointestinal symptoms. Allergic reactions are rare. And most authors report, that treatment with BEs is well tolerated and the registered side effects in BE- and placebo groups are similar. PMID- 27671823 TI - Natural Withanolides in the Treatment of Chronic Diseases. AB - Withanolides, and in particular extracts from Withania somnifera, have been used for over 3,000 years in traditional Ayurvedic and Unani Indian medical systems as well as within several other Asian countries. Traditionally, the extracts were ascribed a wide range of pharmacologic properties with corresponding medical uses, including adaptogenic, diuretic, anti-inflammatory, sedative/anxiolytic, cytotoxic, antitussive, and immunomodulatory. Since the discovery of the archetype withaferin A in 1965, approximately 900 of these naturally occurring, polyoxygenated steroidal lactones with 28-carbon ergostane skeletons have been discovered across 24 diverse structural types. Subsequently, extensive pharmacologic research has identified multiple mechanisms of action across key inflammatory pathways. In this chapter we identify and describe the major withanolides with anti-inflammatory properties, illustrate their role within essential and supportive inflammatory pathways (including NF-kappaB, JAK/STAT, AP 1, PPARgamma, Hsp90 Nrf2, and HIF-1), and then discuss the clinical application of these withanolides in inflammation-mediated chronic diseases (including arthritis, autoimmune, cancer, neurodegenerative, and neurobehavioral). These naturally derived compounds exhibit remarkable biologic activity across these complex disease processes, while showing minimal adverse effects. As novel compounds and analogs continue to be discovered, characterized, and clinically evaluated, the interest in withanolides as a novel therapeutic only continues to grow. PMID- 27671824 TI - Gambogic Acid and Its Role in Chronic Diseases. AB - Kokum, a spice derived from the fruit of the Garcinia hanburyi tree, is traditionally used in Ayurvedic medicines to facilitate digestion and to treat sores, dermatitis, diarrhoea, dysentery, and ear infection. One of the major active components of kokum is gambogic acid, also known as guttic acid, guttatic acid, beta-guttilactone, and beta-guttiferin. Gambogic acid's anti-proliferative, anti-bacterial; antioxidant and anti-inflammatory effects result from its modulation of numerous cell-signaling intermediates. This chapter discusses the sources, chemical components, mechanism of action, and disease targets of the kokum spice. PMID- 27671825 TI - Embelin and Its Role in Chronic Diseases. AB - Embelia ribes Burm of Myrsinaceae family has been widely used as an herb in the traditional medicine of India. Embelin is an active component extracted from the fruits of Embelia ribes. It has a wide spectrum of biological activities and is not toxic at low dose. This review focuses on the physical-chemical properties and bioactivities of Embelin, as well as its effects on chronic diseases such as tumors, autoimmune inflammatory diseases, parasitic infections, microbial infections, diabetes, obesity, and cardio-cerebral vascular diseases. The underlying mechanisms of the effects are also discussed. As a multiple-targeted therapeutic agent, Embelin has the potential to be used widely for the treatment of a variety of chronic diseases, including malignant tumors. PMID- 27671826 TI - Butein and Its Role in Chronic Diseases. AB - Natural compounds isolated from various plant sources have been used for therapeutic purpose for centuries. These compounds have been routinely used for the management of various chronic ailments and have gained considerable attention because of their significant efficacy and comparatively low side effects. Butein, a chacolnoid compound that has been isolated from various medicinal plants has exhibited a wide range of beneficial pharmacological effects, such as anti inflammatory, anticancer, antioxidant, and anti-angiogenic in diverse disease models. This article briefly summarizes the past published literature related to the therapeutic and protective effects of butein, as demonstrated in various models of human chronic diseases. Further analysis of its important cellular targets, toxicity, and pharmacokinetic profile may further significantly expand its therapeutic application. PMID- 27671827 TI - Garcinol and Its Role in Chronic Diseases. AB - The various bioactive compounds isolated from leaves and fruits of Garcinia sps plants, have been characterized and experimentally demonstrated to be anti oxidant, anti-inflammatory and anti-cancer in nature. Garcinol, a polyisoprenylated benzophenone, obtained from plant Garcinia indica has been found to be an effective inhibitor of several key regulatory pathways (e.g., NF kB, STAT3 etc.) in cancer cells, thereby being able to control malignant growth of solid tumours in vivo. Despite its high potential as an anti-neoplastic modulator of several cancer types such as head and neck cancer, breast cancer, hepatocellular carcinoma, prostate cancer, colon cancer etc., it is still in preclinical stage due to lack of systematic and conclusive evaluation of pharmacological parameters. While it is promising anti-cancer effects are being positively ascertained for therapeutic development, studies on its effectiveness in ameliorating other chronic diseases such as cardiovascular diseases, diabetes, allergy, neurodegenerative diseases etc., though seem favourable, are very recent and require in depth scientific investigation. PMID- 27671828 TI - Morin and Its Role in Chronic Diseases. AB - Chronic diseases can be referred to the long-term medical conditions which are mostly progressive in nature, i.e., it deteriorates over time. Diabetes, arthritis, heart disease, stroke, cancer, and chronic respiratory problems (e.g., COPD) are not a few examples of chronic diseases and chronic diseases are the leading causes of death and disability all over the world. Chronic diseases and conditions are among the most common, costly, and preventable of all health problems. Affordable cost, presence mostly in the consumables, and minimal side effects make the naturally occurring compounds interesting and attractive for pharmacological study in recent years. Plants produce diverse types of low molecular weight products mainly for the defense purpose. Among them, the group of secondary metabolites related to a polyphenolic group has been named flavonoids and are of great interest due to their incredible pharmacological properties. In these regard, due to its potent anti-inflammatory, anti-apoptotic and many important pharmacological properties (relevant to chronic diseases, e.g., urate transporter inhibitor related to gout, modulator of immunosystem related to chronic hypersensitivity, etc.), morin [morin hydrate:2-(2,4 dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopy ran-4-one; 3,5,7,20,40 pentahydroxyflavone], widely found among the Moraceae family, considered as one of the most important key bioflavonols. However, little is known about the molecular mechanisms of its action on such conditions. In this chapter, we have summarized most of the findings, if not all, available till date. PMID- 27671829 TI - Ellagic Acid and Its Role in Chronic Diseases. AB - Ellagic acid is a natural anti-oxidant phenol found in numerous fruits and vegetables, in particular pomegranate, persimmon, raspberry, black raspberry, strawberry, peach, plumes, nuts (walnuts, almonds), and wine. The anti proliferative and anti-oxidant properties of ellagic acid have prompted research into its potential health benefits. The aim of this chapter will be to summarize potential benefits of ellagic acid supplementation in chronic diseases. PMID- 27671830 TI - The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. PMID- 27671831 TI - Triggering receptor expressed on myeloid cells 1 (TREM-1) and cytokine gene variants in complicated and uncomplicated malaria. AB - BACKGROUND: Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells 1 (TREM-1) enhances inflammatory responses by increasing secretion of IL-8 and other Th1 cytokines. In contrast, TREM-like transcript 1 (TREML-1) promotes anti-inflammatory responses by binding to TREM-1 ligands and competing with TREM-1, thus antagonizing TREM-1 activation to reduce inflammation. Endothelial protein C receptor (EPCR) also mediates anti-inflammatory responses by activating endothelial protein C (PC). Upon microbial stimulation, soluble forms of TREM-1 (sTREM-1) and soluble EPCR (sEPCR) are released. Their plasma levels reflect the degree of inflammation and the severity of infection. METHODS: In a cross-sectional study comparing patients with severe with uncomplicated malaria, sTREM-1, soluble TREML-1 (sTREML-1) and sEPCR plasma levels as well as plasma levels of sEPCR derived from convalescent patients were quantified. Samples were collected on admittance of paediatric patients infected with Plasmodium falciparum to hospitals in Accra, Ghana. Distinct genetic regions of the genes encoding TREM-1, EPCR, interleukin (IL)-8 and IL-18 encompassing known genetic polymorphisms that influence plasma levels underwent DNA sequencing. RESULTS: Higher sTREM-1 levels were observed among children suffering from severe malaria compared to those with uncomplicated malaria (P = 0.049). Low TREM-1 to TREML-1 ratios were associated with uncomplicated malaria (P = 0.033). The TREM1 rs2234237T variant causing the amino acid exchange Thr25Ser, which has been associated with higher TREM-1 plasma levels, was significantly more frequent among patients with severe malaria than in those with uncomplicated malaria (P = 0.036). Low levels of sEPCR were observed in severe and uncomplicated malaria, while variant genotypes of IL8, IL18 and EPCR did not show any association. CONCLUSION: Higher plasma levels of sTREM-1 alone or relative to sTREML-1 during malaria predispose to the phenotype of severe malaria. Carriage of the TREM1 rs2234237T allele appears to be a risk factor for the development of severe malaria. PMID- 27671832 TI - 1 H-Detected Solid-State NMR Studies of Water-Inaccessible Proteins In Vitro and In Situ. AB - 1 H detection can significantly improve solid-state NMR spectral sensitivity and thereby allows studying more complex proteins. However, the common prerequisite for 1 H detection is the introduction of exchangeable protons in otherwise deuterated proteins, which has thus far significantly hampered studies of partly water-inaccessible proteins, such as membrane proteins. Herein, we present an approach that enables high-resolution 1 H-detected solid-state NMR (ssNMR) studies of water-inaccessible proteins, and that even works in highly complex environments such as cellular surfaces. In particular, the method was applied to study the K+ channel KcsA in liposomes and in situ in native bacterial cell membranes. We used our data for a dynamic analysis, and we show that the selectivity filter, which is responsible for ion conduction and highly conserved in K+ channels, undergoes pronounced molecular motion. We expect this approach to open new avenues for biomolecular ssNMR. PMID- 27671834 TI - Salicylic acid (SA)-eluting bone regeneration scaffolds with interconnected porosity and local and sustained SA release. AB - In previous work, we observed that localized and sustained delivery of an anti inflammatory drug, salicylic acid (SA), via a SA-based polymer (SAP) powder significantly enhanced diabetic bone regeneration through long-term mitigation of local inflammation. In this study, SAP was formulated into uniform microspheres and then sintered into a scaffold with an interconnected porous structure and modulus suitable for bone regeneration. The SAP scaffolds have ~45% SA loading, which is the highest among drug-eluting bone regeneration scaffolds to-date. In addition, the scaffold provides localized, controlled and sustained SA release that has been proven to enhance diabetic bone regeneration. With the combination of physical (interconnected porosity) and chemical therapeutic features (high drug loading and sustained release), the novel SAP scaffolds offer unique therapeutic advantages and are promising diabetic bone regeneration candidates. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 311-318, 2017. PMID- 27671833 TI - Effect of metal-cation antacids on the pharmacokinetics of 1200 mg raltegravir. AB - OBJECTIVES: Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once-daily regimen (QD) at a dose of 1200 mg is under development. The effect of calcium carbonate and magnesium/aluminium hydroxide antacids on the pharmacokinetics of a 1200 mg dose of raltegravir was assessed in this study. METHODS: An open-label, four-period, four-treatment, fixed-sequence study in 20 HIV-infected patients was performed. Patients needed to be on raltegravir as part of a stable treatment regimen for HIV, and upon entry into the trial received 5 days of 1200 mg raltegravir as pretreatment, before they entered the four-period study: 1200 mg of raltegravir alone (period 1), calcium carbonate antacid as TUMS(r) Ultra Strength (US) 1000 and 1200 mg raltegravir given concomitantly (Period 2), magnesium/aluminium hydroxide antacid as 20 ml MAALOX(r) Maximum Strength substitute MS given 12 h after administration of 1200 mg raltegravir (period 3), and calcium carbonate antacid as TUMS(r) US 1000 given 12 h after administration of 1200 mg raltegravir (period 4). Patients received their dose of 1200 mg QD raltegravir during the intervals between periods to re establish steady state. AUC0-24 , C24 , Cmax and Tmax were calculated from the individual plasma concentrations of 1200 mg QD raltegravir after administration alone or with a calcium carbonate antacid or with a staggered dose of a calcium carbonate antacid or magnesium/aluminium hydroxide antacid. Adverse events, in addition to laboratory safety tests (haematology, serum chemistry and urinalysis), 12-lead electrocardiograms and vital signs were assessed. KEY FINDINGS: All treatments were well tolerated in the study. Metal-cation antacids variably affected the pharmacokinetics of 1200 mg QD raltegravir. When calcium carbonate antacid was given with 1200 mg raltegravir concomitantly, the geometric mean ratio (GMR) and its associated 90% confidence interval (90% CI) for AUC0-24 , Cmax and C24 h were 0.28 (0.24, 0.32), 0.26 (0.21, 0.32) and 0.52 (0.45, 0.61), respectively. When calcium carbonate antacid and magnesium/aluminium hydroxide were given 12 h after raltegravir 1200 mg QD dosing, the GMR (90% CI) values for AUC0-24 and Cmax were 0.90 (0.80, 1.03), 0.98 (0.81, 1.17), and 0.86 (0.73, 1.03), 0.86 (0.65, 1.15), respectively. However, significant reduction in the trough concentrations of raltegravir was observed: C24 h 0.43 (0.36, 0.51) in the presence of calcium carbonate antacids and 0.42 (0.34, 0.52) in presence of magnesium/aluminium hydroxide, respectively. CONCLUSIONS: Overall, the use of metal-cation antacids with 1200 mg QD raltegravir is not recommended. PMID- 27671835 TI - Enterostomy-related complications and growth following reversal in infants. AB - BACKGROUND: Infant enterostomies are used to manage various neonatal surgical conditions where it is not suitable or safe to form a primary anastomosis. Complications are common and there is no consensus regarding optimal timing of enterostomy reversal. Stoma reversal is thought to allow patients to thrive; however, this has not been demonstrated robustly. AIM: The study aimed to identify risk factors for enterostomy-related complications and to determine the relationship between enterostomy complications, enterostomy reversal and weight gain in infants with enterostomies. METHODS: A retrospective case note review of 58 infants who underwent enterostomy formation and reversal during a 6-year period was undertaken; demographic data, diagnosis, enterostomy complications and serial weights were noted. Standardised growth charts were used to calculate z scores. RESULTS: Enterostomy complications were documented in 24 infants (41%). Infants of low birth weight and low gestational birth age were significantly more likely to have an enterostomy-related complication (1110 vs 2125 g, 28.5 vs 35 weeks, respectively); they were more likely to have longer inpatient stays and remain dependent on parenteral nutrition prior to closure (median 92.5 vs 52 days, 40% vs 16%, respectively). Irrespective of diagnosis, gestation and presence of an enterostomy complication, the mean z score prior to enterostomy closure was -0.747 vs +0.892 following closure. CONCLUSIONS: Around 40% of infants with an enterostomy will have an enterostomy-related complication. Whatever their weight, gestation or underlying pathology, most infants thrive after enterostomy closure and this should be considered when planning the optimal timing for this procedure. PMID- 27671836 TI - Two-hourly versus 3-hourly feeding for very low birthweight infants: a randomised controlled trial. AB - OBJECTIVE: To determine whether feeding with 2-hourly or 3-hourly feeding interval reduces the time to achieve full enteral feeding and to compare their outcome in very low birthweight preterm infants. DESIGN: Parallel-group randomised controlled trial with a 1:1 allocation ratio. SETTING: Two regional tertiary neonatal intensive care units. PATIENTS: 150 preterm infants less than 35 weeks gestation with birth weight between 1.0 and 1.5 kg were recruited. INTERVENTIONS: Infants were enrolled to either 2-hourly or 3-hourly interval feeding after randomisation. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was time to achieve full enteral feeding (>=100 mL/kg/day). Secondary outcomes include time to regain birth weight, episode of feeding intolerance, peak serum bilirubin levels, duration of phototherapy, episode of necrotising enterocolitis, nosocomial sepsis and gastro-oesophageal reflux. RESULTS: 72 infants were available for primary outcome analysis in each group as three were excluded due to death-three deaths in each group. The mean time to full enteral feeding was 11.3 days in the 3 hourly group and 10.2 days in the 2-hourly group (mean difference 1.1 days; 95% CI -0.4 to 2.5; p=0.14). The mean time to regain birth weight was shorter in 3 hourly group (12.9 vs 14.8 days, p=0.04). Other subgroup analyses did not reveal additional significant results. No difference in adverse events was found between the groups. CONCLUSION: 3-hourly feeding was comparable with 2-hourly feeding to achieve full enteral feeding without any evidence of increased adverse events. TRIAL REGISTRATION NUMBER: ACTRN12611000676910, pre-result. PMID- 27671837 TI - Maternal cardiovascular function at 35-37 weeks' gestation: relation to maternal characteristics. AB - OBJECTIVE: To examine the possible effects of maternal characteristics and obstetric and medical history on maternal cardiovascular parameters at 35-37 weeks' gestation. METHODS: In 3013 singleton pregnancies at 35-37 weeks, maternal characteristics and medical history were recorded; uterine artery pulsatility index, mean arterial pressure (MAP) and maternal cardiovascular parameters were measured. Multivariable regression analysis was used to determine significant predictors of the cardiovascular parameters among gestational age (GA), maternal characteristics and medical history. RESULTS: Multivariable regression analysis demonstrated that significant independent prediction of log10 cardiac output and log10 cardiac power was provided by GA, maternal age, weight, weight gain from the first trimester, height, racial origin, smoking, assisted conception and previous neonatal birth-weight Z-score in parous women. For log10 total peripheral resistance, significant prediction was provided by GA, maternal age, height, racial origin, chronic hypertension, diabetes mellitus, assisted conception, previous neonatal birth-weight Z-score and prior pre-eclampsia (PE) in parous women. For log10 stroke volume, significant prediction was provided by maternal age, height, racial origin, smoking, chronic hypertension and diabetes mellitus. For heart rate, significant prediction was provided by GA, weight, weight gain, height, racial origin, chronic hypertension, previous neonatal birth weight Z-score and prior PE in parous women. For log10 MAP, significant prediction was provided by maternal weight, racial origin, family history of PE, chronic hypertension and diabetes mellitus. For log10 thoracic fluid capacity, significant prediction was provided by GA, maternal age, weight, height, racial origin and systemic lupus erythematosus or antiphospholipid syndrome. For log10 ventricular ejection time, significant prediction was provided by GA, weight, height and racial origin. CONCLUSION: Maternal cardiovascular parameters are affected by maternal characteristics and medical and obstetric history, and they should therefore be converted into multiples of the normal median adjusted for significant independent predictors before their inclusion in combined screening for PE. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27671839 TI - Impact of the 2015 El Nino event on winter air quality in China. AB - During the winter of 2015, there was a strong El Nino (ENSO) event, resulting in significant anomalies for meteorological conditions in China. Analysis shows that the meteorological conditions in December 2015 (compared to December 2014) had several important anomalies, including the following: (1) the surface southeasterly winds were significantly enhanced in the North China Plain (NCP); (2) the precipitation was increased in the south of eastern China; and (3) the wind speeds were decreased in the middle-north of eastern China, while slightly increased in the south of eastern China. These meteorological anomalies produced important impacts on the aerosol pollution in eastern China. In the NCP region, the PM2.5 concentrations were significantly increased, with a maximum increase of 80-100 MUg m-3. A global chemical/transport model (MOZART-4) was applied to study the individual contribution of the changes in winds and precipitation to PM2.5 concentrations. This study suggests that the 2015El Nino event had significant effects on air pollution in eastern China, especially in the NCP region, including the capital city of Beijing, in which aerosol pollution was significantly enhanced in the already heavily polluted capital city of China. PMID- 27671838 TI - Ciliated muconodular papillary tumor of the lung: A report of five cases. AB - Ciliated muconodular papillary tumor (CMPT) of the lung is a newly defined and extremely rare tumor characterized by a papillary growth pattern, consisting of ciliated columnar cells, mucous cells, and basal cells with abundant mucin production. Tumor definitions and clinicopathological features continue to be debated. Herein, we report five surgical cases of CMPT to characterize its radiographic, gross, and microscopic features. The five cases involved three male patients aged 80, 67, and 66 years, and two female patients aged 73 and 70 years. Three cases were discovered during health care screenings, and two cases were found during follow-up for another synchronous cancer. Histopathological examination revealed that the tumor tissue was composed of ciliated columnar cells, mucous cells, and basal cells with abundant mucin production. Neither nuclear atypia nor mitotic figures were observed. All patients had good prognoses. The benign histological features and clinical courses in these five cases suggest that CMPT is an independent and benign tumor of the lung. PMID- 27671841 TI - Acid-Base Switchable [2]- and [3]Rotaxane Molecular Shuttles with Benzimidazolium and Bis(pyridinium) Recognition Sites. AB - For the purpose of developing higher level mechanically interlocked molecules (MIMs), such as molecular switches and machines, a new rotaxane system was designed in which both the 1,2-bis(pyridinium)ethane and benzimidazolium recognition templating motifs were combined. These two very different recognition sites were successfully incorporated into [2]rotaxane and [3]rotaxane molecular shuttles which were fully characterized by 1 H NMR, 2D EXSY, single-crystal X-ray diffraction and VT NMR analysis. By utilizing benzimidazolium as both a recognition site and stoppering group it was possible to create not only an acid/base switchable [2]rotaxane molecular shuttle (energy barrier 20.9 kcal?mol 1 ) but also a [3]rotaxane molecular shuttle that displays unique dynamic behavior involving the simultaneous motion of two macrocyclic wheels on a single dumbbell. This study provides new insights into the design of switchable molecular shuttles. Due to the unique properties of benzimidazoles, such as fluorescence and metal coordination, this new type of molecular shuttle may find further applications in developing functional molecular machines and materials. PMID- 27671840 TI - Regression in thin melanoma is associated with nodal recurrence after a negative sentinel node biopsy. AB - Prognostic markers for nodal metastasis in thin melanoma patients are debated. We present a single institution study looking at factors predictive of nodal disease in thin melanoma patients. Retrospective review from 1997 to 2012 identified 252 patients with thin melanoma (<=1 mm) who underwent a sentinel lymph node biopsy (SLNB). Node-positive patients included positive SLNB patients and negative SLNB patients who developed a nodal recurrence (false-negative SLNB). Clinicopathologic characteristics were correlated with nodal status and outcome. Median follow-up was 45.5 months. Twelve of 252 patients (4.8%) were node positive including six positive SLNB (2.4%) and six false-negative SLNB (2.4%) patients. No clinicopathologic factors were significantly correlated with nodal disease. For the six false-negative SLNB patients, median time to nodal recurrence was 37.5 months. Regression was seen in only 16% of cases, but the rate increased to 60% for false-negative SLNB cases. Both age (odds ratio [OR]: 1.09, 95% CI: 1.01-1.17; P = 0.02) and regression (OR: 8.33, 95% CI: 1.34-52.63; P = 0.02) were significantly associated with nodal recurrence after a negative SLNB on univariable analysis. Nodal disease in thin melanoma patients was seen in 4.8% of cases. Although regression was not correlated with nodal metastasis, it was correlated with a false-negative SLNB. Patients with thin melanoma and regression may need more intensive surveillance after a negative SLNB. Further study is needed to determine if the same immune mechanisms that result in regression in primary tumors also lead to regression in lymph nodes, which may decrease detection of melanoma nodal metastases. PMID- 27671842 TI - Sustainable Hydrothermal Carbonization Synthesis of Iron/Nitrogen-Doped Carbon Nanofiber Aerogels as Electrocatalysts for Oxygen Reduction. AB - It is urgent to develop new kinds of low-cost and high-performance nonprecious metal (NPM) catalysts as alternatives to Pt-based catalysts for oxygen reduction reaction (ORR) in fuel cells and metal-air batteries, which have been proved to be efficient to meet the challenge of increase of global energy demand and CO2 emissions. Here, an economical and sustainable method is developed for the synthesis of Fe, N codoped carbon nanofibers (Fe-N/CNFs) aerogels as efficient NPM catalysts for ORR via a mild template-directed hydrothermal carbonization (HTC) process, where cost-effective biomass-derived d(+)-glucosamine hydrochloride and ferrous gluconate are used as precursors and recyclable ultrathin tellurium nanowires are used as templates. The prepared Fe/N-CNFs catalysts display outstanding ORR activity, i.e., onset potential of 0.88 V and half-wave potential of 0.78 V versus reversible hydrogen electrode in an alkaline medium, which is highly comparable to that of commercial Pt/C (20 wt% Pt) catalyst. Furthermore, the Fe/N-CNFs catalysts exhibit superior long-term stability and better tolerance to the methanol crossover effect than the Pt/C catalyst in both alkaline and acidic electrolytes. This work suggests the great promise of developing new families of NPM ORR catalysts by the economical and sustainable HTC process. PMID- 27671843 TI - Experimental factors affecting the robustness of DNA methylation analysis. AB - Diverging methylation frequencies are often reported for the same locus in the same disease, underscoring the need for limiting technical variability in DNA methylation analyses. We have investigated seven likely sources of variability at different steps of bisulfite PCR-based DNA methylation analyses using a fully automated quantitative methylation-specific PCR setup of six gene promoters across 20 colon cancer cell lines. Based on >15,000 individual PCRs, all tested parameters affected the normalized percent of methylated reference (PMR) differences, with a fourfold varying magnitude. Additionally, large variations were observed across the six genes analyzed. The highest variation was seen using single-copy genes as reference for normalization, followed by different amounts of template in the PCR, different amounts of DNA in the bisulfite reaction, and storage of bisulfite converted samples. Finally, when a highly standardized pipeline was repeated, the difference in PMR value for the same assay in the same cell line was on average limited to five (on a 0-100 scale). In conclusion, a standardized pipeline is essential for consistent methylation results, where parameters are kept constant for all samples. Nevertheless, a certain level of variation in methylation values must be expected, underscoring the need for careful interpretation of data. PMID- 27671844 TI - Factors controlling the origin of Cochlodinium polykrikoides blooms along the Goheung coast, South Korea. AB - We investigated the factors influencing the origin of Cochlodinium polykrikoides blooms along the Goheung coast (GH), and compared them to those along the Geoje (GJ) coast and in the East China Sea (ECS) which were used as reference sites. Stratification did not develop in GH during C. polykrikoides blooms, unlike that in GJ. The surface salinity during summer in ECS was equivalent to that of GH, whereas surface temperature and concentration of nutrients in ECS were markedly higher than those in GH or GJ. Thermohaline (or thermal) fronts appeared between the Korea Southern Coastal Water (KSCW) and the outer seawater during C. polykrikoides blooms. The result of numerical simulation models indicated that freshwater from the Yangtze River clearly affected KSCW. As a result, the origin of C. polykrikoides blooms in GH during summer could be attributed to the inflow of seawater from ECS with high water temperature and abundant nutrients. PMID- 27671845 TI - Degradation of crude oil in a contaminated tidal flat area and the resilience of bacterial community. AB - Crude oil spills, Hebei Spirit in South Korea, is considered as one of the worst environmental disasters of the region. Our understanding on activation of oil degrading bacteria and resilience of microbial community in oil contaminated sites are limited due to scarcity of such event. In the present study, tidal flat sediment contaminated by the oil spill were investigated for duration of 13months to identify temporal change in microbial community and functional genes responsible for PAH-degradation. The results showed predominance of previously known oil-degrading genera, such as Cycloclasticus, Alcanivorax, and Thalassolituus, displaying significant increase within first four months of the accident. The disturbance caused by the oil spill altered the microbial community and its functional structures, but they were almost restored to the original state after 13months. Present study demonstrated high detoxification capacity of indigenous bacterial populations in the tidal flat sediments and its resilience of microbial community. PMID- 27671846 TI - Characterization of phosphorus sorption on the sediments of Yangtze River Estuary and its adjacent areas. AB - This paper studied the kinetics, isotherm and thermodynamics of phosphorus sorption onto the sediments of the Yangtze River estuary and its adjacent waters, as well as the sediments' compositions and physicochemical properties. The process could be described well by a two-compartment first order equation. The sorbed phosphorus mainly consisted of Ex-P and Fe-P, with Ex-P being the dominant. The equilibrium isotherms could be fitted well with a modified Langmuir equation. The calculations of the thermodynamic parameters indicated that the process was spontaneous and exothermic. The CEC and the fractions of clay, calcite and organic matter were correlated with the sorption parameters, while the surface proton charge of the sediments was significantly negatively correlated with them. Considering the kinetics and phosphorus forms changes during the process, the sorption in our study could be considered that the physical process plays an important role. PMID- 27671847 TI - Mesenchymal Stromal Cell Secretion of Programmed Death-1 Ligands Regulates T Cell Mediated Immunosuppression. AB - Mesenchymal stromal cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells of innate and adaptive immune systems. As MSCs become accepted as a therapeutic option for the treatment of immunological disorders such as Graft versus Host Disease, our need to understand the intricate details by which they exert their effects is crucial. Programmed death-1 (PD-1) is an important regulator in T cell activation and homeostatic control. It has been reported that this pathway may be important in contact-dependent mediated immunomodulation by MSCs. The aim of this study was to establish whether MSCs, in addition to their cell-surface expression, are able to secrete PD-1 ligands (PD L1 and PD-L2) and their potential importance in modulating contact-independent mechanisms of MSC immunosuppression. Here we report that MSCs express and secrete PD-L1 and PD-L2 and that this is regulated by exposure to interferon gamma and tumor necrosis factor alpha. MSCs, via their secretion of PD-1 ligands, suppress the activation of CD4+ T cells, downregulate interleukin-2 secretion and induce irreversible hyporesponsiveness and cell death. Suppressed T cells demonstrated a reduction in AKT phosphorylation at T308 and a subsequent increase in FOXO3 expression that could be reversed with blockade of PD-L1. In conclusion, we demonstrate for the first time, that MSCs are able to secrete PD-1 ligands, with this being the first known report of a biological role for PD-L2 in MSCs. These soluble factors play an important role in modulating immunosuppressive effects of MSCs directly on T cell behavior and induction of peripheral tolerance. Stem Cells 2017;35:766-776. PMID- 27671849 TI - Unusual Facial "Acne": A Quiz. PMID- 27671848 TI - Expanded graphite embedded with aluminum nanoparticles as superior thermal conductivity anodes for high-performance lithium-ion batteries. AB - The development of high capacity and long-life lithium-ion batteries is a long term pursuing and under a close scrutiny. Most of the researches have been focused on exploring electrode materials and structures with high store capability of lithium ions and at the same time with a good electrical conductivity. Thermal conductivity of an electrode material will also have significant impacts on boosting battery capacity and prolonging battery lifetime, which is, however, underestimated. Here, we present the development of an expanded graphite embedded with Al metal nanoparticles (EG-MNPs-Al) synthesized by an oxidation-expansion process. The synthesized EG-MNPs-Al material exhibited a typical hierarchical structure with embedded Al metal nanoparticles into the interspaces of expanded graphite. The parallel thermal conductivity was up to 11.6 W.m-1.K-1 with a bulk density of 453 kg.m-3 at room temperature, a 150% improvement compared to expanded graphite (4.6 W.m-1.K-1) owing to the existence of Al metal nanoparticles. The first reversible capacity of EG-MNPs-Al as anode material for lithium ion battery was 480 mAh.g-1 at a current density of 100 mA.g 1, and retained 84% capacity after 300 cycles. The improved cycling stability and system security of lithium ion batteries is attributed to the excellent thermal conductivity of the EG-MNPs-Al anodes. PMID- 27671850 TI - Shedding Light on Shingles: The Power of Prevention. AB - Shingles, or herpes zoster (HZ), is a common secondary infection caused by a reactivated varicella zoster virus (VZV). More than 95% of immunocompetent individuals aged at least 50 years are seropositive for VZV and are therefore at risk for developing HZ. Age-related increased incidence of HZ and its complications are thought to be related to the decline in cell-mediated immunity. Complications of HZ, which create a significant patient and economic burden, may be neurological, ophthalmological, dermatological, or visceral. HZ vaccination is essential for the prevention of HZ and its consequences. This CME activity reviews the clinical presentations and complications of HZ as well as discusses strategies for prevention (Online access: http://courses.elseviercme.com/shingles/626). PMID- 27671851 TI - Science Alone Is Not Enough. PMID- 27671852 TI - The Reply. PMID- 27671853 TI - One More Fact to Know About Inpatient Glycemic Control. PMID- 27671854 TI - The Reply. PMID- 27671856 TI - The Reply. PMID- 27671855 TI - Organic Chemistry: A Vital Part of Basic Understanding of Disease. PMID- 27671857 TI - Don't Overlook the Role of Intraabdominal Pressure. PMID- 27671858 TI - Caprini Score in Hospitalized Medical Patients. PMID- 27671859 TI - The Reply. PMID- 27671861 TI - Preoperative embolization of meningiomas with polyvinyl alcohol particles: The benefits are not outweighed by risks. AB - PURPOSE: The purpose of this study was to define the feasibility, the efficacy and the safety of preoperative embolization (POE) of meningiomas using polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: Between January 2006 and June 2014, 191 consecutive patients were referred to our institution for the treatment of meningiomas; of these 57 patients were excluded from the study. A total of 64 patients (22 men and 42 women) with a mean age of 58.4+/-10.8 [SD] years (range: 14-82years) who underwent POE with PVA particles, achieving extensive (>90%) devascularization were ultimately included and compared to 70 patients who had surgery without POE. Surgical time and intraoperative blood loss were compared between the two groups. The duration of procedures and complications related to POE were analyzed. RESULTS: No differences were found between the two groups with respect to intraoperative blood loss. A significant reduction in surgical time was observed for the group who had POE (207.4+/-79.5 [SD] min vs. 226.9+/-117.6 [SD] min; P=0.028). In a subgroup analysis, the size and location of meningiomas did not influence these results. The duration of procedures was 41.4+/-10.5 [SD] min. Minor complications related to POE occurred in 3 out of 64 patients (4.7%). CONCLUSION: POE of meningiomas using PVA particles is effective in reducing surgical time, when extensive tumor devascularization is achieved. However, radiation exposure, the duration of procedures and complications related to POE with PVA particles do not justify this technique in most patients. PMID- 27671862 TI - Plasma fetuin-A/alpha2-HS-glycoprotein correlates negatively with inflammatory cytokines, chemokines and activation biomarkers in individuals with type-2 diabetes. AB - BACKGROUND: Fetuin-A/AHSH is a novel hepatokine that acts as a vascular calcification inhibitor and as an endogenous TLR-4 ligand. Fetuin-A may act as a positive or negative acute phase protein (APP) in disease conditions. The relationship between circulatory fetuin-A and inflammatory biomarkers in type-2 diabetes (T2D) remains controversial. Therefore, the purpose of this study was to determine the plasma fetuin-A levels in 53 T2D (BMI = 29.7 +/- 4.5 kg/m2) and 72 non-diabetic individuals (BMI = 28.2 +/- 5.8 kg/m2) using premixed 38-plex MAP human cytokine/chemokine magnetic bead immunoassays and the data (mean +/- SEM) were statistically analyzed to determine Pearson's correlation (r) between fetuin A and detected analytes; P-values <=0.05 were considered significant. RESULTS: The data show that plasma fetuin-A levels were comparable in both groups (P = 0.27) and in T2D individuals, fetuin-A associated negatively (P <= 0.05) with a large number of proinflammatory cytokines/chemokines and activation biomarkers including TNF-alpha, IFN-alpha2, IFN-gamma, IL-1alpha, IL-1beta, IL-1RA, IL-3, IL 4, IL-7, IL-9, IL-12p40/p70, IL-15, CCL-2, CCL-4, CCL-11, CCL-22, CXCL-8, CX3CL 1, EFF-2, EGF, G-CSF, GM-CSF, GRO, sCD40L, and VEGF. In non-diabetics, fetuin-A also correlated positively with certain TH2 cytokines (IL-5, IL-13) and chemokines (CCL-3, CCL-5, CCL-7). Notably, in vitro fetuin-A production was significantly suppressed in HepG2 cells treated with TNF-alpha, IL-1beta, and IFN gamma which supported the clinical findings of a negative association between fetuin A and inflammatory mediators. CONCLUSIONS: The negative association between circulatory fetuin-A and systemic inflammatory mediators in T2D patients suggests that plasma fetuin-A may have predictive significance as a negative APP in metabolic disease. PMID- 27671860 TI - MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis. AB - MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD-CD27- memory B-cell population in ACPA+ RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-alpha, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA. PMID- 27671863 TI - pH/multichannel impedance monitoring in patients with laryngo-pharyngeal reflux symptoms - Prediction of therapy response in long-term follow-up. AB - BACKGROUND AND STUDY AIM: Optimal therapy concepts in patients with laryngo pharyngeal reflux (LPR) are still under discussion. Aim of this study was to evaluate long term symptom relief according to results in combined pH/multichannel impedance (MII) monitoring to predict therapy response and symptom relief during long term follow-up. PATIENTS AND METHODS: In patients with predominant LPR symptoms, pH/MII monitoring and subsequent proton pump inhibitor (PPI) therapy were evaluated retrospectively after a minimum follow-up period of 36months. Patients were asked to complete symptom based questionnaires. RESULTS: 45 patients were evaluated and classified according to results of pH/MII. Twenty one patients showed a pathological finding in pH/MII. These patients reported significantly higher LPR-symptom intensity scores and a significantly higher LPR symptom-induced impairment of everyday life scores compared to patients with normal pH/MII monitoring at baseline and at follow-up. PPI associated symptom relief was significantly higher in patients with pathologic pH/MII monitoring (p=0.003). CONCLUSION: In conclusion, combined pH/MII monitoring can reliably predict therapy response to PPIs in LPR patients. With negative results, PPI therapy should be avoided. This approach should be assessed in future prospective clinical trials. PMID- 27671864 TI - Challenging drug target for Parkinson's disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins. AB - The hallmarks of Parkinson's disease and other synucleinopathies, Tubulin Polymerization Promoting Protein (TPPP/p25) and alpha-synuclein (SYN) have two key features: they are disordered and co-enriched/co-localized in brain inclusions. These Neomorphic Moonlighting Proteins display both physiological and pathological functions due to their interactions with distinct partners. To achieve the selective targeting of the pathological TPPP/p25-SYN but not the physiological TPPP/p25-tubulin complex, their interfaces were identified as a specific innovative strategy for the development of anti-Parkinson drugs. Therefore, the interactions of TPPP/p25 with tubulin and SYN were characterized which suggested the involvements of the 178-187 aa and 147-156 aa segments in the complexation of TPPP/p25 with tubulin and SYN, respectively. However, various truncated and deletion mutants reduced but did not abolish the interactions except one mutant; in addition synthetized fragments corresponding to the potential binding segments of TPPP/p25 failed to interact with SYN. In fact, the studies of the multiple interactions at molecular and cellular levels revealed the high conformational plasticity, chameleon feature, of TPPP/p25 that ensures exceptional functional resilience; the lack of previously identified binding segments could be replaced by other segments. The experimental results are underlined by distinct bioinformatics tools. All these data revealed that although targeting chameleon proteins is a challenging task, nevertheless, the validation of a drug target can be achieved by identifying the interface of complexes of the partner proteins existing at the given pathological conditions. PMID- 27671865 TI - Inter-laboratory consistency and variability in the buccal micronucleus cytome assay depends on biomarker scored and laboratory experience: results from the HUMNxl international inter-laboratory scoring exercise. AB - The buccal micronucleus cytome (BMNcyt) assay in uncultured exfoliated epithelial cells from oral mucosa is widely applied in biomonitoring human exposures to genotoxic agents and is also proposed as a suitable test for prescreening and follow-up of precancerous oral lesions. The main limitation of the assay is the large variability observed in the baseline values of micronuclei (MNi) and other nuclear anomalies mainly related to different scoring criteria. The aim of this international collaborative study, involving laboratories with different level of experience, was to evaluate the inter- and intra-laboratory variations in the BMNcyt parameters, using recently implemented guidelines, in scoring cells from the same pooled samples obtained from healthy subjects (control group) and from cancer patients undergoing radiotherapy (treated group). The results indicate that all laboratories correctly discriminated samples from the two groups by a significant increase of micronucleus (MN) and nuclear bud (NBUD) frequencies and differentiated binucleated (BN) cells, associated with the exposure to ionizing radiation. The experience of the laboratories was shown to play an important role in the identification of the different cell types and nuclear anomalies. MN frequency in differentiated mononucleated (MONO) and BN cells showed the greatest consistency among the laboratories and low variability was also detected in the frequencies of MONO and BN cells. A larger variability was observed in classifying the different cell types, indicating the subjectivity in the interpretation of some of the scoring criteria while reproducibility of the results between scoring sessions was very good. An inter-laboratory calibration exercise is strongly recommended before starting studies with BMNcyt assay involving multiple research centers. PMID- 27671866 TI - Device Therapies for Resistant Hypertension. AB - PURPOSE: Resistant hypertension (RH) is a major and growing public health problem. While noncompliance to antihypertensive medication is a major concern in RH patients, it is estimated that even with adequate multi-drug regimens, approximately 10% of patients diagnosed with hypertension fulfill the criteria of true RH. Patients with sustained blood pressure (BP) elevation display high risk for development of target organ damage and associated cardiovascular morbidity and mortality. While optimized pharmacologic therapy, including the use of mineralocorticoid receptor antagonists to guideline-based antihypertensive drug therapy, is effective for improving BP control in this patient cohort, a sizable proportion of RH patients' BP remains uncontrolled, and alternative therapeutic strategies are warranted. METHODS: In the past few years, device-based approaches have been studied extensively. Among these, robust clinical experience in patients with RH exists for renal denervation, baroreflex activation therapy, central arteriovenous anastomosis, and, to a lesser extent, deep brain stimulation. Carotid body modulation is the most recent approach under clinical investigation. The common aim of these approaches is direct targeting of relevant pathophysiologic mechanisms involved in BP control, most commonly activation of the sympathetic nervous system. FINDINGS: This review article briefly summarizes relevant clinical and experimental evidence and highlights the potential utility, as well as limitations, of each approach. IMPLICATIONS: Several device-based approaches show promise in the treatment of RH and have been associated with improved BP control, while generally finding an acceptable side effect profile. Ongoing research is addressing relevant issues relating to patient selection and technical and procedural aspects, and will help to define the future role of device-based approaches for RH in the next few years. PMID- 27671867 TI - Impact of CHA2DS2VASc Score on Candidacy for Anticoagulation in Patients With Atrial Fibrillation: A Multi-payer Analysis. AB - PURPOSE: The purpose of this study is to report on the effect of using CHA2DS2VASc (congestive heart failure, hypertension, age >=75 years [doubled], type 1 or type 2 diabetes mellitus, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) rather than CHADS2 (congestive heart failure, hypertension, age >=75 years, diabetes mellitus, and prior stroke) to determine candidacy for anticoagulant prophylaxis in insured patients with atrial fibrillation (AF). METHODS: Six administrative claims databases that included medical and pharmacy claims for patients aged >=18 years with a new or existing diagnosis of AF and patient outcomes assessed for 1 year after diagnosis were analyzed. Retrospective health plan data analyses were performed using a software tool (Anticoagulant Quality Improvement Analyzer). Study measures included stroke risk (identified by CHADS2 and CHA2DS2VASc scores), bleeding risk (identified by the Anticoagulation and Risk Factors in Atrial Fibrillation score), and anticoagulant use. FINDINGS: A total of 115,906 patients with AF (range of mean ages among the 6 databases, 56 79 years) met the inclusion criteria. All ranges reported represent the minimum and maximum values among the 6 databases. Using the CHA2DS2VASc compared with the CHADS2 index to assess stroke risk resulted in a 23% to 32% increase in patients considered potential candidates for anticoagulant prophylaxis. This translated to a 38% to 114% increase in the number of ostensibly undertreated patients. Among patients with high stroke and low bleeding risk, 18% to 28% more patients were considered potential candidates for anticoagulation treatment using CHA2DS2VASc compared with CHADS2, or a 57% to 151% increase in the number of undertreated patients. IMPLICATIONS: Use of the CHA2DS2VASc score to determine the risk of stroke increased the number of AF patients for whom oral anticoagulation would be recommended. Additional research is needed to determine whether this paradigm shift to greater use of oral anticoagulants improves patient outcomes. PMID- 27671868 TI - Use of low tube voltage and low contrast agent concentration yields good image quality for aortic CT angiography. AB - AIM: To evaluate the impact of a "double-low" imaging protocol (low tube voltage and low contrast agent concentration) on image quality and radiation dose for aortic computed tomography (CT) angiography (CTA). MATERIALS AND METHODS: This was a prospective study of 72 patients undergoing aortic CTA. They were randomised to the double-low and conventional CT (control) groups (n=36/group). Axial imaging was performed in the study group, and control patients were scanned with the conventional protocol. Double-low parameters were: 80-100 kV, 200 mAs, 128*0.625 collimation, 1-mm section thickness, 0.5-mm increments, 300 mm field of view (FOV), iohexol (300 mg iodine/ml, 1-1.5 ml/kg, injected at 4-5 ml/s). Control CT parameters were: 120 kV, 200-300 mAs, iopamidol (370 mg iodine/ml; 1 1.5 ml/kg, injected at 4-5 ml/s); the remaining parameters were the same as in the double-low group. RESULTS: Image noise and quality scores of the double-low and control groups were 15.05+/-1.53 versus 14.67+/-1.53 and 3.52+/-0.51 versus 3.44+/-0.5 (both p>0.05), respectively. Radiation dose was 56% lower in the double-low group compared to control patients (6.76+/-1.08 versus 15.48+/-1.01 mSv, p<0.001). Iodine intake per-capita in the double-low group was 18% lower compared to the control group (300.25+/-7.2 versus 367.86+/-5.54 mgI/kg, p<0.001). CONCLUSIONS: The "double-low" technique for aortic CTA significantly reduced the doses of radiation and iodine contrast agent, while maintaining good image quality. PMID- 27671869 TI - Ultrastructure of the salivary glands in Lithobius forficatus (Myriapoda, Chilopoda, Lithobiidae) according to seasonal and circadian rhythms. AB - The salivary glands (mandibular epidermal glands) of adult males and females of Lithobius forficatus (Myriapoda, Chilopoda) were isolated during spring, summer and autumn. In addition, the organs were isolated at different times of the day - at about 12:00 (noon) and about 00:00 (midnight). The ultrastructure of these organs depending on seasonal and circadian rhythms was analyzed using transmission and scanning electron microscopy and histochemical methods. The paired salivary glands of L. forficatus are situated in the vicinity of the foregut and they are formed by numerous acini that are surrounded by the fat body, hemocytes and tracheolae. The salivary glands are composed of a terminal acinar component and a system of tubular ducts that are lined with a cuticle. The glandular part is composed of secretory epithelial cells that are at various stages of their secretory activity. The saliva that is produced by the secretory cells of the acini is secreted into the salivary ducts, which are lined with a simple epithelium that is based on the non-cellular basal lamina. The ultrastructural variations suggest that salivary glands function differently depending on seasonal rhythms and prepare the animal for overwintering. Therefore, the salivary glands of the centipedes that were analyzed participate in the accumulation of proteins, lipids and polysaccharides during the spring, summer and autumn. Subtle differences in the ultrastructure of the secretory cells of the salivary glands during the circadian cycle must be related to the physiological reactions of the organism. The salivary ducts showed no differences in the specimens that were analyzed during the day/night cycle or during the seasonal cycle. PMID- 27671870 TI - Validity and reliability of the Turkish version of the pressure ulcer prevention knowledge assessment instrument. AB - STUDY AIM: Sound knowledge of pressure ulcers is important to enable good prevention. There are limited instruments assessing pressure ulcer knowledge. The Pressure Ulcer Prevention Knowledge Assessment Instrument is among the scales of which psychometric properties have been studied rigorously and reflects the latest evidence. This study aimed to evaluate the validity and reliability of the Turkish version of the Pressure Ulcer Prevention Knowledge Assessment Instrument (PUPKAI-T), an instrument that assesses knowledge of pressure ulcer prevention by using multiple-choice questions. MATERIALS AND METHODS: Linguistic validity was verified through front-to-back translation. Psychometric properties of the instrument were studied on a sample of 150 nurses working in a tertiary hospital in Istanbul, Turkey. RESULTS: The content validity index of the translated instrument was 0.94, intra-class correlation coefficients were between 0.37 and 0.80, item difficulty indices were between 0.21 and 0.88, discrimination indices were 0.20-0.78, and the Kuder Richardson for the internal consistency was 0.803. CONCLUSIONS: The PUPKAI-T was found to be a valid and reliable tool to evaluate nurses' knowledge on pressure ulcer prevention. The PUPKAI-T may be a useful tool for determining educational needs of nurses on pressure ulcer prevention. PMID- 27671871 TI - A timecourse analysis of systemic and gonadal effects of temperature on sexual development of the red-eared slider turtle Trachemys scripta elegans. AB - Temperature dependent sex determination (TSD) is the process by which the environmental temperature experienced during embryogenesis influences the sex of an organism, as in the red-eared slider turtle Trachemys scripta elegans. In accord with current paradigms of vertebrate sex determination, temperature is believed to exert its effects on sexual development in T. scripta entirely within the middle third of development, when the gonad is forming. However, whether temperature regulates the transcriptome in T. scripta early embryos in a manner that could influence secondary sex characteristics or establish a pro-male or pro female environment has not been investigated. In addition, apart from a handful of candidate genes, very little is known about potential similarities between the expression cascade during TSD and the genetic cascade that drives mammalian sex determination. Here, we conducted an unbiased transcriptome-wide analysis of the effects of male- and female-promoting temperatures on the turtle embryo prior to gonad formation, and on the gonad during the temperature sensitive period. We found sexually dimorphic expression reflecting differences in steroidogenic enzymes and brain development prior to gonad formation. Within the gonad, we mapped a cascade of differential expression similar to the genetic cascade established in mammals. Using a Hidden Markov Model based clustering approach, we identified groups of genes that show heterochronic shifts between M. musculus and T. scripta. We propose a model in which multiple factors influenced by temperature accumulate during early gonadogenesis, and converge on the antagonistic regulation of aromatase to canalize sex determination near the end of the temperature sensitive window of development. PMID- 27671874 TI - The WWC Attrition Standard: Sensitivity to Assumptions and Opportunities for Refining and Adapting to New Contexts. AB - BACKGROUND: To limit the influence of attrition bias in assessments of intervention effectiveness, several federal evidence reviews have established a standard for acceptable levels of sample attrition in randomized controlled trials. These evidence reviews include the What Works Clearinghouse (WWC), the Home Visiting Evidence of Effectiveness Review, and the Teen Pregnancy Prevention Evidence Review. We believe the WWC attrition standard may constitute the first use of model-based, empirically supported bounds on attrition bias in the context of a federally sponsored systematic evidence review. Meeting the WWC attrition standard (or one of the attrition standards based on the WWC standard) is now an important consideration for researchers conducting studies that could potentially be reviewed by the WWC (or other evidence reviews). OBJECTIVES: The purpose of this article is to explain the WWC attrition model, how that model is used to establish attrition bounds, and to assess the sensitivity of attrition bounds to key parameter values. RESEARCH DESIGN: Results are based on equations derived in the article and values generated by applying those equations to a range of parameter values. RESULTS: The authors find that the attrition boundaries are more sensitive to the maximum level of bias that an evidence review is willing to tolerate than to other parameters in the attrition model. CONCLUSIONS: The authors conclude that the most productive refinements to existing attrition standards may be with respect to the definition of "maximum tolerable bias." PMID- 27671873 TI - Three-dimensional microCT imaging of mouse development from early post implantation to early postnatal stages. AB - In this work, we report the use of iodine-contrast microCT to perform high throughput 3D morphological analysis of mouse embryos and neonates between embryonic day 8.5 to postnatal day 3, with high spatial resolution up to 3um/voxel. We show that mouse embryos at early stages can be imaged either within extra embryonic tissues such as the yolk sac or the decidua without physically disturbing the embryos. This method enables a full, undisturbed analysis of embryo turning, allantois development, vitelline vessels remodeling, yolk sac and early placenta development, which provides increased insights into early embryonic lethality in mutant lines. Moreover, these methods are inexpensive, simple to learn and do not require substantial processing time, making them ideal for high throughput analysis of mouse mutants with embryonic and early postnatal lethality. PMID- 27671872 TI - Cerebrovascular defects in Foxc1 mutants correlate with aberrant WNT and VEGF-A pathways downstream of retinoic acid from the meninges. AB - Growth and maturation of the cerebrovasculature is a vital event in neocortical development however mechanisms that control cerebrovascular development remain poorly understood. Mutations in or deletions that include the FOXC1 gene are associated with congenital cerebrovascular anomalies and increased stroke risk in patients. Foxc1 mutant mice display severe cerebrovascular hemorrhage at late gestational ages. While these data demonstrate Foxc1 is required for cerebrovascular development, its broad expression in the brain vasculature combined with Foxc1 mutant's complex developmental defects have made it difficult to pinpoint its function(s). Using global and conditional Foxc1 mutants, we find 1) significant cerebrovascular growth defects precede cerebral hemorrhage and 2) expression of Foxc1 in neural crest-derived meninges and brain pericytes, though not endothelial cells, is required for normal cerebrovascular development. We provide evidence that reduced levels of meninges-derived retinoic acid (RA), caused by defects in meninges formation in Foxc1 mutants, is a major contributing factor to the cerebrovascular growth defects in Foxc1 mutants. We provide data that suggests that meninges-derived RA ensures adequate growth of the neocortical vasculature via regulating expression of WNT pathway proteins and neural progenitor derived-VEGF-A. Our findings offer the first evidence for a role of the meninges in brain vascular development and provide new insight into potential causes of cerebrovascular defects in patients with FOXC1 mutations. PMID- 27671875 TI - Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets. AB - Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). The present work describes two novel single-domain antibodies (VHHs or nanobodies) that specifically recognize extracellular amyloid deposits and intracellular tau neurofibrillary tangles, the two core lesions of Alzheimer's disease (AD). Following intravenous administration in transgenic mouse models of AD, in vivo real-time two-photon microscopy showed gradual extravasation of the VHHs across the BBB, diffusion in the parenchyma and labeling of amyloid deposits and neurofibrillary tangles. Our results demonstrate that VHHs can be used as specific BBB-permeable probes for both extracellular and intracellular brain targets and suggest new avenues for therapeutic and diagnostic applications in neurology. PMID- 27671876 TI - ECM-based macroporous sponges release essential factors to support the growth of hematopoietic cells. AB - The success of hematopoietic stem cells (HSCs) transplantation is limited due to the low number of HSCs received from donors. In vivo, HSCs reside within a specialized niche inside the 3D porous spongy bone. The natural environment in the niche is composed of structural proteins, glycosaminoglycans (GAGs) and soluble factors that control cells fate. However, the designed scaffolds for in vitro culture do not fairly recapitulate this microenvironment and cannot efficiently control HSCs fate. Here we report on the development of new omental ECM-based 3D macroporous sponges for hematopoietic cell culture. The scaffolds' structure, porosity and stability were characterized and optimized. Analysis of the biochemical content revealed that they were composed of collagens and GAGs, including sulfated GAGs. This morphology and composition enabled growth factors interaction with the sulfated GAGs, as indicated by the high loading capacity and release profile of three different hematopoietic niche factors. Finally, the ability of the ECM-based scaffolds to efficiently support the growth of hematopoietic cells by releasing stem cell factor (SCF) was demonstrated. PMID- 27671877 TI - Preliminary evaluation of child self-rating using the Child Tourette Syndrome Impairment Scale. AB - AIM: To evaluate and compare how children with Tourette syndrome and parents rate tic and non-tic behavioral related impairment in home, school, and social domains; to compare these with clinician tic ratings; and to identify factors that may predict greater impairment. METHOD: In a sample of 85 Tourette syndrome and 92 healthy control families, the Child Tourette Syndrome Impairment Scale, designed for parent-report and which includes 37 items rated for tic and non-tic impairment, was administered to parents and, with the referent modified, to children ages 9 to 17 years. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS). Analyses utilized descriptive and multivariate statistics. RESULTS: Tourette syndrome children's and parents' impairment ratings were higher than HC (p<0.001) and correlated moderately (r=0.46 to 0.54; p<0.001). Children's and parents' tic impairment ratings correlated with YGTSS (r=0.36 to 0.37; p<0.001). Parents' average ratings were higher than children's for 19 tic and all 37 non-tic impairment items. For 29 items, children self-rated impairment higher for tics than non-tics. Diagnoses of attention-deficit hyperactivity disorder and obsessive-compulsive disorder had larger effects on parent impairment ratings. INTERPRETATION: The Child Tourette Syndrome Impairment Scale appears informative for child self-rating in Tourette syndrome. PMID- 27671878 TI - Emotional context during encoding modulates recognition electrophysiological activity. AB - The aim of the study was to determine whether experiencing a non-emotional event in a positive or negative emotional context affected recognition of the event and the related electrophysiological activity. Twenty-eight adults participated in a betting-game task in which they could win (positive emotional context) or lose (negative emotional context) money. The participants also completed a non-betting task (non-emotional context). Afterward, the participants completed an old/new recognition task for faces with neutral expressions that were encoded during the betting and non-betting game. Event-related potentials and autonomic responses were recorded. The stimuli learned in the positive emotional context were better recognized than those learned in the non-emotional context. The FN400, the parietal old/new effect and the late frontal old/new effect were modulated by positive valence. Learning information under a positive emotional condition enhances its later recognition and the brain activity that underlies this process. PMID- 27671879 TI - Genetic Characterization of a Multifocal Ganglioglioma Originating Within the Spinal Cord. AB - BACKGROUND: Gangliogliomas are rare, low-grade intra-axial tumors that exhibit both neuronal and glial components. Although the vast majority present as an intracranial lesion, a rare subset exist as isolated lesions of the spinal cord. Gangliogliomas have also been shown to harbor mutations in the p53 tumor suppressor gene and BRAF oncogene. Previous studies in ganglioglioma have correlated p53 mutations with histologic transformation and BRAF mutations with worse prognosis. CASE DESCRIPTION: In this report, we describe a 35-year-old female who presented with multifocal ganglioglioma, involving both the conus medullaris and filum terminale. The dominant lesion in the filum terminale was resected, which revealed World Health Organization I grade, p53 mutant, and BRAF wildtype status. Our study documents the first report of a multifocal ganglioglioma, originating within the spinal cord. CONCLUSIONS: Importantly, this case contradicts previous reports of p53 and BRAF mutations portending worsened tumor behavior and prognosis and demonstrates that further studies are needed to delineate the role of genetic characterization in the biologic understanding and management of gangliogliomas. PMID- 27671880 TI - Neurosurgical Infection Rates and Risk Factors: A National Surgical Quality Improvement Program Analysis of 132,000 Patients, 2006-2014. AB - BACKGROUND: The existing body of literature on postoperative neurosurgical infections lacks large multicenter reports on postoperative neurosurgical infections. This is the largest study to date of postoperative neurosurgical infections rates, time to event, and risk factors. METHODS: Demographics, medical history, and postoperative infections were assessed for all adult patients in the large, randomized, multicenter American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database undergoing an operation with a surgeon whose primary specialty was neurological surgery from 2006 to 2014. RESULTS: Of 3,723,797 cases from 517 institutions in the NSQIP from 2006 to 2014, 132,063 neurosurgery cases were identified. Within these patients, the 30-day rate of postoperative infections was 5.3%. Postoperatively, 1.8% of patients developed surgical site infections (SSI), and 3.9% developed other infections including pneumonia and urinary tract infections. Superficial SSI had a cumulative incidence of 0.8% at a median of 16 (interquartile range [IQR], 11-22) days. Pneumonia had a cumulative incidence of 1.4% at a median of 5 days (IQR, 2 10 days). Systemic inflammatory response syndrome had a cumulative incidence of 1.6% at a median of 3 days (IQR, 8-16 days). Predictors of postoperative infections on multivariable analysis included female sex, older age, obesity, functionally dependent status before surgery, ventilator dependence, preoperative steroid use, bleeding disorders, hyponatremia, lymphocytosis, anemia, thrombocytosis, emergent case status, wound class II-IV, American Society of Anesthesiologists class 3-5, and longer operative times. CONCLUSION: The overall ACS-NSQIP reported rate of postoperative infections was 5.3% from 2006 to 2014. Multivariable analysis demonstrated several predictive factors for postoperative infections. PMID- 27671881 TI - Time Course of Resolution of Hyperprolactinemia After Transsphenoidal Surgery Among Patients Presenting with Pituitary Stalk Compression. AB - BACKGROUND: Primary lactotroph disinhibition, or stalk effect, occurs when mechanical compression of the pituitary stalk disrupts the tonic inhibition by dopamine released by the hypothalamus. The resolution of pituitary stalk effect related hyperprolactinemia postoperatively has not been studied in a large cohort of patients. We performed a retrospective review to investigate the time course of recovery of lactotroph disinhibition after transsphenoidal surgery. METHODS: Medical records were retrospectively reviewed for all patients undergoing transsphenoidal surgery with the senior author from April 2008 to November 2014. RESULTS: Of 556 pituitary adenomas, 289 (52.0%) were eliminated: 77 (13.9%) had an immunohistochemically confirmed prolactinoma, 119 (21.4%) patients had previous surgery, 93 (16.7%) had incomplete medical records, leaving 267 patients (48.0%) for final analysis. Of these patients, 72 (27.0%) had increased serum prolactin levels (>=23.3 ng/mL), suggestive of pituitary stalk effect (maximum prolactin level = 148.0 ng/mL). Patients with stalk effect were more likely than those with normal serum prolactin levels to present with menstrual dysfunction (29.7% vs. 19.4%; P < 0.01) and galactorrhea (11.1% vs. 2.1%; P < 0.01). Patients with lactotroph disinhibition were more likely to harbor macroadenomas than were patients who did not show lactotroph disinhibition (81.9% vs. 70.2%; P = 0.06). Among patients with increased preoperative prolactin, 77.8% experienced normalization of serum prolactin postoperatively, galactorrhea improved in 100%, sexual dysfunction resolved in 66.6%, and menstrual dysfunction among premenopausal females normalized in 73.3% at last follow-up (mean, 5.35 years; range, 0.1-10 years). CONCLUSIONS: Transsphenoidal surgery can provide durable normalization of serum prolactin levels and related symptoms caused by pituitary stalk compression-related lactotroph disinhibition. PMID- 27671882 TI - The Results of Surgical Treatment of Cushing Tumors in the Republic of Uzbekistan: Establishing Transsphenoidal Surgery in A Developing Nation. AB - BACKGROUND: Transsphenoidal surgery (TSS) was introduced into the Republic of Uzbekistan in 2005 and has been developing since then. The principal center for the management of all pituitary disease is a single site for a nation with a population of approximately 30 million. Results in surgery for Cushing disease are a marker of surgical technical skill in TSS. All previously published series come from the developed world, where sophisticated investigations and management are available. Many of these investigations are not available in Uzbekistan. METHODS: This mixed series of 154 patients from 2000 to 2013 presents the data from Uzbekistan. The management of Cushing disease before the introduction of TSS was with unilateral adrenalectomy, a procedure virtually unknown in the West. It reduces cortisol burden but is, in the long-term, only a temporary measure because it allows the tumor to continue to grow. The results of this procedure are presented and show that in the short-term, surprisingly reasonable remission is obtained. RESULTS: These results are contrasted with the experience with TSS, for which the impact of the input from an experienced team including an endocrinologist and neurosurgeon from the United Kingdom allowed a transformation in management and enabled outcomes to match what can be expected in the West. CONCLUSIONS: TSS for Cushing's Disease achieved an early remission of 68.7% (early morning cortisol of <50 nmol/L), although 4 patients relapsed. PMID- 27671883 TI - Use of a Zero-Profile Device for Contiguous 2-Level Anterior Cervical Diskectomy and Fusion: Comparison with Cage with Plate Construct. AB - BACKGROUND: A new zero-profile, standalone device (Zero P) was recently developed and has shown a lower incidence rate of complications and competitive clinical outcomes compared with anterior cervical cage with plate construct (CP) in single and multilevel anterior cervical diskectomy and fusion (ACDF). However, there is still concern whether Zero P is appropriate for multilevel ACDF. In addition, there have been few reports of contiguous 2-level ACDF used in conjunction with Zero P. METHODS: We reviewed contiguous 2-level ACDF performed from December 2006 to February 2015. A total of 63 patients met inclusion criteria for the study (CP group = 32 cases; Zero P group = 31 cases). All preoperative and postoperative clinical and radiologic parameters were recorded. These parameters were compared between both groups. RESULTS: The postoperative change of Cobb S over time in the Zero P group was significantly different from that in the CP group. The maintenance of Cobb S in the Zero P group was better than that in the CP group (P < 0.05). The maintenance of anterior intervertebral disk height (IDH) at postoperative assessment for the Zero P group was significantly better than that in the CP group (P < 0.05). Within-group comparison of the postoperative change of anterior and posterior IDH over time revealed that the anterior IDH was significantly lower than the posterior IDH in the Zero P group (P < 0.05). CONCLUSION: For 2-level contiguous ACDF, the use of a zero-profile device has the capacity to show compatible outcomes in correction and maintenance of segmental angle if the anterior titanium alloy plate is properly positioned at the anterior vertebral line. PMID- 27671884 TI - Development of De Novo Arteriovenous Malformation Following Ischemic Stroke: Case Report and Review of Current Literature. AB - BACKGROUND: Arteriovenous malformations (AVMs) are hypothesized to be static, congenital lesions developing as early as 4 weeks of fetal life. New literature has shown that AVMs may represent dynamic and reactive vascular lesions arising from cerebral infarction, inflammation, or trauma. A literature search reveals 17 previously reported cases of new AVM formation after previous negative imaging studies. This reactive development or "second hit" theory suggests that at a molecular level, growth factors may play a vital role in aberrant angiogenesis and maturation of an arteriovenous fistula into an AVM. CASE DESCRIPTION: A 52 year-old female presented with a ruptured left frontal AVM demonstrated by computed tomography angiography and digital subtraction angiography. The patient had suffered an acute ischemic stroke in the similar cerebral vascular territory 8 years prior due to left internal carotid artery occlusion. Detailed neuroimaging at that time failed to reveal any vascular malformation, suggesting that the AVM might have developed in response to initial vascular insult. CONCLUSIONS: We believe that there might exist a subset of AVMs that display dynamic characteristics and could potentially appear, grow, or resolve spontaneously without intervention, especially in the presence of local growth factors and molecular signaling cascades. When combined with a previous cerebral insult such as stroke, trauma, or inflammation, de novo AVM formation may represent a "second hit" with abnormal angiogenesis and vessel formation. PMID- 27671885 TI - General Anesthesia Versus Local Anesthesia in Stereotactic Biopsies of Brain Lesions: A Prospective Randomized Study. AB - BACKGROUND: Stereotactic biopsy of brain lesions with unknown entities is a common neurosurgical procedure to obtain tumor tissue. Pathologists can then provide an exact diagnosis on which further therapy, such as resection, radiotherapy, or chemotherapy, can be based. These procedures can be performed under local or general anesthesia. In this prospective study, we aim to show whether stress levels are higher for patients who undergo stereotactic biopsy under local or general anesthesia. METHODS: Between January 2013 and December 2014, we screened 157 patients. Of these, 43 were included and evaluated in this study. Twenty-one patients gave their written consent and were randomized for either local or general anesthesia. A Post Traumatic Stress Score (PTSS) questionnaire was filled out by the patients preoperatively and postoperatively. Also, patients who did not agree to randomization had an opportunity to fill out the PTSS questionnaire. Twenty-two patients agreed only to fill out the stress level questionnaire but refused randomization. These patients were evaluated as a subgroup. Scores achieved in the PTSS were compared by using the Fisher exact test. RESULTS: Among the randomized patients, 9 underwent the procedure under local anesthesia and 12 under general anesthesia. Median PTSS was 24 preoperatively in the patients who received local anesthesia versus 20 among the patients with general anesthesia (P = 0.37; Fisher exact test). Postoperatively, PTSS was 29.5 in median for patients with local anesthesia versus 23 for patients with general anesthesia (P = 0.30; Fisher exact test). Postoperatively, the PTSS showed a median increase of 5.5 points in the LA and 3 points in the GA group (P = 0.87; Fisher exact test). P values of 0.05 and lower were considered statistically significant. CONCLUSIONS: The willingness of patients to undergo randomization in this setting was low (13.3%). Within this highly selective group of patients, there was no significant difference for stress levels in patients who underwent stereotactic biopsy under local anesthesia versus general anesthesia. However, median values indicate a trend for higher stress-level values for patients undergoing local anesthesia. PMID- 27671886 TI - Factors for Overall Survival in Patients with Skull Base Chordoma: A Retrospective Analysis of 225 Patients. AB - BACKGROUND: Although a controversial and complex issue, the prognostic factors of skull base chordomas are worth exploring. METHODS: Prognostic factors associated with overall survival (OS) were retrospectively estimated in an individual cohort of skull base chordomas prospectively maintained for 10 years by a Kaplan-Meier method and univariate Cox proportional hazards model. Multivariate analysis by Cox regression analysis was performed to identify the independent prognostic factors. A nomogram was then formulated by R software based on the results. RESULTS: A total of 180 primary patients and 45 recurrent cases were included, with a mean follow-up period of 43.7 months (range, 4-127 months). The OS of the primary group at 5 years and 7 years was 84% and 78%, and the mean OS was 103.8 months, which was significantly longer than the recurrent group, in which the mean postrecurrent OS was 68.4 months. In the primary group, preoperative Karnofsky Performance Status (KPS) score (P = 0.004) and a decline of perioperative KPS score (P = 0.015) were identified as independent predictors of OS. A nomogram was contracted to predict 5-year, and 7-year OS, which was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.74). In the recurrent group, visual deficit was verified as an independent risk factor associated with postrecurrent OS (P = 0.014). CONCLUSIONS: Both pathologic and perioperative KPS score evaluations are significant in OS prediction of both primary and recurrent cases. The nomogram for primary lesions, consisting of preoperative functional status and its perioperative changes, appears useful for risk stratification of long-term survival. PMID- 27671887 TI - Management Scheme for Cerebral Wegener Granulomatosis: An Unusual Pseudotumoral Skull Base Pathology. AB - Granulomatosis with polyangiitis (Wegener disease) is a rare antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis that seldom involves brain and meninges. We present a case of a 35-year-old woman with granulomatosis with polyangiitis involving the brain and the meninges. The histologic diagnosis required a complete resection of the lesion. Despite the possibility of postoperative wound infection, surgery was mandatory to ascertain the diagnostic and to treat locally. PMID- 27671888 TI - Thinking about Thinking: 28 Years On. PMID- 27671889 TI - Antimicrobial activity and regulation of CXCL9 and CXCL10 in oral keratinocytes. AB - Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10 are dysregulated in oral inflammatory conditions, and it is not known if these chemokines target microorganisms that form oral biofilm. The aim of this study was to investigate the antimicrobial activity of CXCL9 and CXCL10 on oral microflora and their expression profiles in oral keratinocytes following exposure to inflammatory and infectious stimuli. Streptococcus sanguinis was used as a model and Escherichia coli as a positive control. The antimicrobial effect of CXCL9/CXCL10 was tested using a radial diffusion assay. mRNA transcripts were isolated from lipopolysaccharide (LPS)-treated and untreated (control) oral keratinocyte cell lines at 2-, 4-, 6-, and 8-h time-points of culture. The CXCL9/10 expression profile in the presence or absence of interferon-gamma (IFN-gamma) was assessed using semiquantitative PCR. Although both chemokines demonstrated antimicrobial activity, CXCL9 was the most effective chemokine against both S. sanguinis and E coli. mRNA for CXCL10 was expressed in control cells and its production was enhanced at all time-points following stimulation with LPS. Conversely, CXCL9 mRNA was not expressed in control or LPS-stimulated cells. Finally, stimulation with IFN-gamma enhanced basal expression of both CXCL9 and CXCL10 in oral keratinocytes. Chemokines derived from oral epithelium, particularly CXCL9, demonstrate antimicrobial properties. Bacterial and inflammatory-stimulated up regulation of CXCL9/10 could represent a key element in oral bacterial colonization homeostasis and host-defense mechanisms. PMID- 27671890 TI - Angiogenesis in alkaptonuria. AB - Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Here, we investigated the presence of neoangiogenesis in AKU synovium and healthy controls. Synovium from AKU patients, who had undergone total joint replacement or arthroscopy, or from healthy patients without any history of rheumatic diseases, who underwent surgical operation following sport trauma was subjected to hematoxylin and eosin staining. Histologic grades were assigned for clinical disease activity and synovitis based on cellular content of the synovium. By immunofluorescence microscopy, using different endothelial cell markers, we observed large vascularization in AKU but not in healthy synovium. Moreover, Western blotting and quantification analyses confirmed strong expression of endothelial cell markers in AKU synovial tissues. Importantly, AKU synovium vascular endothelium expressed high levels of beta-dystroglycan, a protein previously involved in the regulation of angiogenesis in osteoarthritic synovium. This is the first report providing experimental evidences that new blood vessels are formed in AKU synovial tissues, opening new perspectives for AKU therapy. PMID- 27671892 TI - Sphingolipid biosynthesis upregulation by TOR complex 2-Ypk1 signaling during yeast adaptive response to acetic acid stress. AB - Acetic acid-induced inhibition of yeast growth and metabolism limits the productivity of industrial fermentation processes, especially when lignocellulosic hydrolysates are used as feedstock in industrial biotechnology. Tolerance to acetic acid of food spoilage yeasts is also a problem in the preservation of acidic foods and beverages. Thus understanding the molecular mechanisms underlying adaptation and tolerance to acetic acid stress is increasingly important in industrial biotechnology and the food industry. Prior genetic screens for Saccharomyces cerevisiae mutants with increased sensitivity to acetic acid identified loss-of-function mutations in the YPK1 gene, which encodes a protein kinase activated by the target of rapamycin (TOR) complex 2 (TORC2). We show in the present study by several independent criteria that TORC2 Ypk1 signaling is stimulated in response to acetic acid stress. Moreover, we demonstrate that TORC2-mediated Ypk1 phosphorylation and activation is necessary for acetic acid tolerance, and occurs independently of Hrk1, a protein kinase previously implicated in the cellular response to acetic acid. In addition, we show that TORC2-Ypk1-mediated activation of l-serine:palmitoyl-CoA acyltransferase, the enzyme complex that catalyzes the first committed step of sphingolipid biosynthesis, is required for acetic acid tolerance. Furthermore, analysis of the sphingolipid pathway using inhibitors and mutants indicates that it is production of certain complex sphingolipids that contributes to conferring acetic acid tolerance. Consistent with that conclusion, promoting sphingolipid synthesis by adding exogenous long-chain base precursor phytosphingosine to the growth medium enhanced acetic acid tolerance. Thus appropriate modulation of the TORC2-Ypk1-sphingolipid axis in industrial yeast strains may have utility in improving fermentations of acetic acid-containing feedstocks. PMID- 27671891 TI - Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. AB - Inherited methylation disorders are a group of rarely reported, probably largely underdiagnosed disorders affecting transmethylation processes in the metabolic pathway between methionine and homocysteine. These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. This paper provides the first consensus recommendations for the diagnosis and management of methylation disorders. Following search of the literature and evaluation according to the SIGN-methodology of all reported patients with methylation defects, graded recommendations are provided in a structured way comprising diagnosis (clinical presentation, biochemical abnormalities, differential diagnosis, newborn screening, prenatal diagnosis), therapy and follow-up. Methylation disorders predominantly affect the liver, central nervous system and muscles, but clinical presentation can vary considerably between and within disorders. Although isolated hypermethioninemia is the biochemical hallmark of this group of disorders, it is not always present, especially in early infancy. Plasma S adenosylmethionine and S-adenosylhomocysteine are key metabolites for the biochemical clarification of isolated hypermethioninemia. Mild hyperhomocysteinemia can be present in all methylation disorders. Methylation disorders do not qualify as primary targets of newborn screening. A low methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 MUmol/L. There is some evidence that this diet may also be beneficial in patients with S adenosylhomocysteine hydrolase and adenosine kinase deficiencies. S adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. Recommendations given in this article are based on general principles and in practice should be adjusted individually according to patient's age, severity of the disease, clinical and laboratory findings. PMID- 27671893 TI - Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cells in vitro. AB - Glyoxalase 1 (Glo1) is a cytoplasmic enzyme with a cytoprotective function linked to metabolism of the cytotoxic side product of glycolysis, methylglyoxal (MG). It prevents dicarbonyl stress - the abnormal accumulation of reactive dicarbonyl metabolites, increasing protein and DNA damage. Increased Glo1 expression delays ageing and suppresses carcinogenesis, insulin resistance, cardiovascular disease and vascular complications of diabetes and renal failure. Surprisingly, gene trapping by the International Mouse Knockout Consortium (IMKC) to generate putative Glo1 knockout mice produced a mouse line with the phenotype characterised as normal and healthy. Here, we show that gene trapping mutation was successful, but the presence of Glo1 gene duplication, probably in the embryonic stem cells (ESCs) before gene trapping, maintained wild-type levels of Glo1 expression and activity and sustained the healthy phenotype. In further investigation of the consequences of dicarbonyl stress in ESCs, we found that prolonged exposure of mouse ESCs in culture to high concentrations of MG and/or hypoxia led to low-level increase in Glo1 copy number. In clinical translation, we found a high prevalence of low-level GLO1 copy number increase in renal failure where there is severe dicarbonyl stress. In conclusion, the IMKC Glo1 mutant mouse is not deficient in Glo1 expression through duplication of the Glo1 wild-type allele. Dicarbonyl stress and/or hypoxia induces low-level copy number alternation in ESCs. Similar processes may drive rare GLO1 duplication in health and disease. PMID- 27671895 TI - Recession may decrease mortality trends. PMID- 27671896 TI - In focus in HCB. PMID- 27671894 TI - Development of a motif-based topology-independent structure comparison method to identify evolutionarily related folds. AB - Structure conservation, functional similarities, and homologous relationships that exist across diverse protein topologies suggest that some regions of the protein fold universe are continuous. However, the current structure classification systems are based on hierarchical organizations, which cannot accommodate structural relationships that span fold definitions. Here, we describe a novel, super-secondary-structure motif-based, topology-independent structure comparison method (SmotifCOMP) that is able to quantitatively identify structural relationships between disparate topologies. The basis of SmotifCOMP is a systematically defined super-secondary-structure motif library whose representative geometries are shown to be saturated in the Protein Data Bank and exhibit a unique distribution within the known folds. SmotifCOMP offers a robust and quantitative technique to compare domains that adopt different topologies since the method does not rely on a global superposition. SmotifCOMP is used to perform an exhaustive comparison of the known folds and the identified relationships are used to produce a nonhierarchical representation of the fold space that reflects the notion of a continuous and connected fold universe. The current work offers insight into previously hypothesized evolutionary relationships between disparate folds and provides a resource for exploring novel ones. Proteins 2016; 84:1859-1874. (c) 2016 Wiley Periodicals, Inc. PMID- 27671897 TI - Blebbishields and mitotic cells exhibit robust macropinocytosis. AB - Cancer stem cells can survive and undergo transformation after apoptosis by initiating robust endocytosis. Endocytosis in-turn drives formation of serpentine filopodia, which promote construction of blebbishields from apoptotic bodies. However, the status and role of macropinocytosis in blebbishields is not known. Here, we show by scanning electron microscopy and by macropinocytosis assays that blebbishields exhibit robust macropinocytosis. Inhibiting dynamin-mediated endocytosis does not affect macropinocytosis in blebbishields or in mitotic cells. In addition, inhibiting macropinocytosis did not inhibit construction of blebbishields from apoptotic bodies. Thus, although apoptotic cancer stem cells exhibit robust macropinocytosis, macropinocytosis is not essential to generate blebbishields, although it may play other roles in blebbishield biology. (c) 2016 BioFactors, 43(2):181-186, 2017. PMID- 27671898 TI - First clinical evaluation of a new single-use flexible ureteroscope (LithoVueTM): a European prospective multicentric feasibility study. AB - INTRODUCTION: We evaluated a new digital single-use flexible ureteroscope, LithoVueTM with respect to deflection, image quality and maneuverability. METHODS: A prospective cohort study was conducted in eight tertiary reference centers in Europe in December 2015 and January 2016. All consecutive patients included underwent flexible ureteroscopy and were 18 years or older. Deflection and image quality pre- and post-use and maneuverability were rated with a Likert scale. RESULTS: A total of 40 procedures were performed (five per institution). The indication for FURS was treatment of renal stones in 92.5 % of the cases. Before LithoVueTM usage, the median measured upward and downward deflections were both 270 degrees . Image quality was rated as "very good" in 65 % of cases and "good" in 30 %. Maneuverability was "very good" in 77.5 % and "good" in 17.5 %. At the final evaluation, median upward and downward deflections were both 270 degrees . Image quality was still "very good" in 65 % of cases and "good" in 30 % with no significant difference compared with preoperative data (p = 1). Maneuverability was "very good" in 72.5 % and "good" in 17.5 %, with no significant difference compared with preoperative data (p = 0.92). Two LithoVueTM broke during surgery (5 %): one occurring in extreme deflection with acute infundibulopelvic angle and spontaneous loss of vision for the second one. CONCLUSION: The LithoVueTM displayed good image quality, active deflection and maneuverability. Further evaluation of surgical outcomes and cost analysis will help to present the best utility of this single-use FURS in current practice. PMID- 27671899 TI - Proctors exploit three-dimensional ghost tools during clinical-like training scenarios: a preliminary study. AB - PURPOSE: In this study, we examine three-dimensional (3D) proctoring tools (i.e., semitransparent ghost tools overlaid on the surgeon's field of view) on realistic surgical tasks. Additionally, we develop novel, quantitative measures of whether proctors exploit the additional capabilities offered by ghost tools. METHODS: Seven proctor-trainee pairs completed realistic surgical tasks such as tissue dissection and suturing in a live porcine model using 3D ghost tools on the da Vinci Xi Surgical System. The usability and effectiveness of 3D ghost tools were evaluated using objective measures of proctor performance based on proctor hand movements and button presses, as well as post-study questionnaires. RESULTS: Proctors exploited the capabilities of ghost tools, such as 3D hand movement (p < 0.001), wristedness (p < 0.001), finger pinch gestures (p < 0.001), and bimanual hand motions (p < 0.001). The median ghost tool excursion distances across proctors in the x-, y-, and z-directions were 57.6, 31.9, and 50.7, respectively. Proctors and trainees consistently evaluated the ghost tools as effective across multiple categories of mentoring. Trainees found ghost tools more helpful than proctors across all categories (p < 0.05). CONCLUSIONS: Proctors exploit the augmented capabilities of 3D ghost tools during clinical-like training scenarios. Additionally, both proctors and trainees evaluated ghost tools as effective mentoring tools, thereby confirming previous studies on simple, inanimate tasks. Based on this preliminary work, advanced mentoring technologies, such as 3D ghost tools, stand to improve current telementoring and training technologies in robot assisted minimally invasive surgery. PMID- 27671900 TI - The protective effects of moderate drinking: lies, damned lies, and... selection biases? PMID- 27671902 TI - Neurodegeneration in multiple sclerosis and neuromyelitis optica. AB - Multiple sclerosis (MS) and neuromyelitis optica (NMO) are autoimmune demyelinating diseases of the central nervous system (CNS), having distinct immunological and pathological features. They have two pathogenic components, 'inflammation' and 'neurodegeneration', with different degrees of severity and pathogenetic mechanisms. The target antigen of autoimmunity in NMO is the water channel aquaporin-4 (AQP4), and antibodies directed against this antigen result in astrocyte damage. MS is a disease primarily affecting myelin and oligodendrocytes, but thus far, no MS-specific autoantigen has been identified. The distinct inflammatory processes in these diseases may trigger cascades of events leading to disease-specific neurodegeneration. Damage of the CNS tissue appears to be amplified by mechanisms that are in part shared by the two conditions and involve oxidative burst activation in microglia/macrophages, mitochondrial damage and axonal energy failure, Wallerian degeneration and meningeal inflammation. However, they appear to differ regarding the nature of the inflammatory response, the type and extent of cortical injury, and the type of astrocyte reaction and damage. Here, we provide a detailed comparison of the pathology between MS and NMO, which may help to define shared and disease specific mechanisms of neurodegeneration in these diseases. PMID- 27671903 TI - Giant anterior urethral calculus associated with urethrocutaneous fistula in an elderly man. PMID- 27671901 TI - Statins are underused in recent-onset Parkinson's disease with increased vascular risk: findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts. AB - BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately. OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD severity and phenotype. METHODS: Cardiovascular risk was quantified using the QRISK2 calculator (high >=20%, medium >=10 and <20%, low risk <10%). Motor severity and phenotype were assessed using the Movement Disorder Society Unified PD Rating Scale (UPDRS) and cognition by the Montreal cognitive assessment. RESULTS: In 2909 individuals with recent-onset PD, the mean age was 67.5 years (SD 9.3), 63.5% were men and the mean disease duration was 1.3 years (SD 0.9). 33.8% of cases had high vascular risk, 28.7% medium risk, and 22.3% low risk, while 15.2% of cases had established CVD. Increasing vascular risk and CVD were associated with older age (p<0.001), worse motor score (p<0.001), more cognitive impairment (p<0.001) and worse motor phenotype (p=0.021). Statins were prescribed in 37.2% with high vascular risk, 15.1% with medium vascular risk and 6.5% with low vascular risk, which compared with statin usage in 75.3% of those with CVD. CONCLUSIONS: Over 60% of recent-onset PD patients have high or medium cardiovascular risk (meriting statin usage), which is associated with a worse motor and cognitive phenotype. Statins are underused in these patients, compared with those with vascular disease, which is a missed opportunity for preventive treatment. TRIAL REGISTRATION NUMBER: GN11NE062, NCT02881099. PMID- 27671904 TI - Non-modifiable factors predict discharge quality after robotic partial nephrectomy. AB - PURPOSE: To identify predictors of poor discharge quality after robotic partial nephrectomy (RPN) at a large academic center. METHODS: We queried our institutional RPN database for consecutive patients treated between 2011 and 2015. The primary outcome was poor discharge quality, defined as length of stay >3 days and/or unplanned readmission. The association between patient, disease, and provider factors and overall discharge quality was assessed using univariate and multivariable analyses. RESULTS: Of 791 cases, 219 (27.7 %) had poor discharge quality. On univariate analysis, factors associated with poor discharge quality were older age (p < .01), black race (p = .01), social insurance (p < .01), higher ASA score (p < .01), chronic kidney disease (p < .01), increased tumor size (p < .01), and higher tumor complexity (p = .01). Surgeon case volume did not predict discharge quality (p = .63). After adjustment for covariates on multivariable analysis, race (p = .01), ASA (p = .02), CKD (p < .01), tumor size (p = .02), and tumor complexity (p = .03) still predicted poor discharge quality. In particular, the odds of poor discharge quality were highest in the setting of CKD (OR 2.62, 95 % CI 1.72-4.01), black race (OR 2.17, 95 % CI 1.32-3.57), and higher ASA (OR 1.49, 95 % CI 1.07-2.08). CONCLUSIONS: Non-modifiable patient and disease factors predict poor discharge quality after RPN. Risk adjustment for these factors will be important for determining future reimbursement for RPN providers. PMID- 27671905 TI - Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease. AB - BACKGROUND: The proteasome system is involved in several disorders. The 5' untranslated region of PSMA6 gene contains a single nucleotide polymorphism (SNP) -8 C/G, associated with diabetes, myocardial infarction and coronary artery disease. METHODS: We examined 584 patients with end-stage kidney disease (ESKD) and 430 controls. All were genotyped for -8 C/G SNP by polymerase chain reaction and restriction analysis. RESULTS: We observed lower frequency of CG + GG genotypes in patients than in controls (20 vs. 42 %, p = 0.0038). The odds ratio of 0.34 (95 % CI 0.26-0.45) suggests association of CG + GG with decreased risk of ESKD. We investigated the association between PSMA6 polymorphism and LVH present in 54 % of patients. There was a significant association of CG + GG genotype with LVH, with over 75 % of CG + GG in patients with LVH. This effect was independent from other common causes of LVH-age (OR 1.12, p = 0.643) and hypertension (OR 1.72, p = 0.422). CONCLUSION: We demonstrated for the first time that PSMA6 polymorphism might be a protective factor for ESKD. On the other hand, CG + GG genotypes are independently related to LVH in ESKD patients. PMID- 27671906 TI - Correlation between pre- and post-dialysis blood pressure levels in hemodialysis patients with intradialytic hypertension. AB - PURPOSE: To determine the association between arterial systolic blood pressure values at the beginning and at the end of a hemodialysis (HD) session in intradialytic hypertension patients. METHODS: This study evaluated the arterial systolic blood pressure patterns in 154 chronic kidney failure patients; among these patients, 18 were identified as having intradialytic hypertension. In the patients with intradialytic hypertension, four consecutive HD sessions were analyzed in which the systolic, diastolic, mean, and pulse blood pressures were automatically determined every 30 min. RESULTS: A linear relationship was revealed between the systolic blood pressure levels measured after 30 min and those obtained after 240 min of HD (r = 0.3894, p = 0.001). This association became stronger after 90 min (r = 0.5471; p < 0.001), indicating that for intradialytic hypertension patients, systolic blood pressure values at the beginning of HD were correlated with systolic blood pressure values at the end of the session. CONCLUSIONS: For intradialytic hypertension patients, values obtained at the end of HD are correlated with the initial values. This information could facilitate planning and earlier treatment. PMID- 27671908 TI - For the Patient with "Low-risk Chest Pain"-How Low Is Low? PMID- 27671909 TI - Foreword. PMID- 27671911 TI - An update on gastric cancer. PMID- 27671907 TI - Therapy and prognosis of ANCA-associated vasculitis from the clinical nephrologist's perspective. AB - This paper reviews the recently published scientific information regarding ANCA associated vasculitis (AAV), aiming to highlight the most important data from the clinical nephrologists' perspective. The classification, pathomechanism, recent achievements of the treatment, short-term and long-term outcomes of the disease, and the difficulties nephrologists face when taking care for patients with AAV are summarized. There has been significant progress in the understanding of the genetic and pathologic background of the disease in the last years, and results of histological studies guide us to predict long-term renal function. Findings of several multicentered trials with reasonable number of participants provide comparison of the efficacy and safety of different remission induction and maintenance therapies, and evaluate recently introduced immunosuppressive agents. Although the clinical outcome of patients with AAV has improved significantly since modern immunosuppressive drugs are available, the treatment-related complications still contribute to the morbidity and mortality. To improve the survival and quality of life of patients with AAV further, knowledge of the predictors of relapse, end-stage kidney disease, and mortality, also prevention of infections and other treatment-related adverse events are important. The eligibility for renal transplantation and the option for successful pregnancies for young women are also important factors which influence the patients' quality of life. In order to provide favorable outcome, the clinicians need to establish personalized treatment strategies to optimize the intensity and minimize the toxicity of the immunosuppressive therapy. PMID- 27671912 TI - [Well's cellulitis: A case report]. AB - INTRODUCTION: Wells's cellulitis is a rare eosinophilic dermatose characterized by an inflammatory erythematous eruption, often associated with eosinophilia, and suggestive histologic features. The differential diagnosis with other eosinophilic dermatitis is problematic. The treatment is typically based on systemic steroids. CASE REPORT: We report a 63-year-old patient with an extensive pruritic maculo-papular eruption of the limbs and the trunk, forming large indurated and painful erythematous patches. Blood analysis revealed eosinophilia. Histologic examination showed perivascular eosinophilic inflammatory infiltration, also disposed around collagen fibers. The symptoms disappeared with topical corticosteroids. CONCLUSION: The diagnosis of Well's cellulitis is difficult because of the lack of specific sign; it is based on suggestive clinical, biological and histological features. Topical corticosteroids are efficient and well-tolerated, and should be used as first treatment. PMID- 27671913 TI - [Subcutaneous nodules]. PMID- 27671914 TI - Toxicological role of an acyl glucuronide metabolite in diclofenac-induced acute liver injury in mice. AB - The acyl glucuronide (AG) metabolites of carboxylic acid-containing drugs are potentially chemically reactive and are suggested to be implicated in toxicity, including hepatotoxicity, nephrotoxicity and drug hypersensitivity reactions. However, it remains unknown whether AG formation is related to toxicity in vivo. In this study, we sought to determine whether AG is involved in the pathogenesis of liver injury using a mouse model of diclofenac (DIC)-induced liver injury. Mice that were administered DIC alone exhibited significantly increased plasma alanine aminotransferase levels, whereas mice that were pretreated with the UDP glucuronosyltransferase inhibitor (-)-borneol (BOR) exhibited suppressed alanine aminotransferase levels at 3 and 6 h after DIC administration although not significant at 12 h. The plasma DIC-AG concentrations were significantly lower in BOR- and DIC-treated mice than in mice treated with DIC alone. The mRNA expression levels of chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2 and the neutrophil marker CD11b were reduced in the livers of mice that had been pretreated with BOR compared to those that had been administered DIC alone, whereas mRNA expression of the macrophage marker F4/80 was not altered. An immunohistochemical analysis at 12 h samples revealed that the numbers of myeloperoxidase- and lymphocyte antigen 6 complex-positive cells that infiltrated the liver were significantly reduced in BOR- and DIC-treated mice compared to mice that were treated with DIC alone. These results indicate that DIC-AG is partly involved in the pathogenesis of DIC-induced acute liver injury in mice by activating innate immunity and neutrophils. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27671916 TI - Psychological Mechanisms of PTSD and Its Treatment. AB - Psychological mechanisms can be defined as processes or events that are responsible for specific changes in psychological outcomes. In psychotherapy research, mechanisms are the factors through which interventions produce change. In this article, we explain the importance of identifying psychological mechanisms, describe methods for identifying them, and analyze recent literature on the psychological mechanisms underlying the development and treatment of posttraumatic stress disorder (PTSD). Based on the findings of recent investigations (from 2013 to present), we focus on four putative mechanisms: emotional engagement, extinction and contextualization, distress tolerance, and negative posttraumatic cognitions. Future directions for psychological mechanism research are also outlined, including possible opportunities for capitalizing on the most promising mechanisms identified to date. PMID- 27671915 TI - A Slice of the Suicidal Brain: What Have Postmortem Molecular Studies Taught Us? AB - Suicide ranks amongst the leading causes of death worldwide. Contemporary models of suicide risk posit that suicide results from the interaction of distal and proximal factors, including neurobiological, psychological/clinical, and social factors. While a wealth of neurobiological studies aimed at identifying biological processes associated with suicidal behaviour have been conducted over the last decades, the more recent development of arrays and high-throughput sequencing methods have led to an increased capacity and interest in the study of genomic factors. Postmortem studies are a unique tool to directly investigate genomic processes that may be dysregulated in the suicidal brain. In this review, we discuss postmortem literature investigating functional genomic studies of suicide, particularly focusing on epigenetic mechanisms. PMID- 27671917 TI - Emergency Department Screening for Suicide and Mental Health Risk. AB - Suicide is the second leading cause of death among youth ages 10-24. An estimated 1.5 million US adolescents receive their primary health care in the emergency department (ED); this is particularly true for low-income and minority youths who often lack a regular source of care. ED visits can provide a window of opportunity to screen and identify youths with suicide and mental health risk, triage youths based on need, and facilitate effective follow-up care. Recently developed brief therapeutic assessment approaches have demonstrated success in improving rates of follow-up care after discharge from the ED. Furthermore, there is some data supporting clinical benefits when youths receive evidence-based outpatient follow-up care. ED screening combined with effective follow-up, therefore, may provide one strategy for improving mental health and reducing health disparities in our nation. This paper reviews the context in which ED screenings occur, available tools and strategies, and evidence for the effectiveness of tested approaches. PMID- 27671919 TI - Improving Access to Standardized Fertility Preservation Information for Older Adolescents and Young Adults with Cancer: Using a User-Centered Approach with Young Adult Patients, Survivors, and Partners to Refine Fertility Knowledge Transfer. AB - Adolescent and young adult (AYA) cancer patients under 40 should be made aware of their fertility risks and preservation options throughout their care. However, discussions on fertility preservation (FP) do not routinely occur. With a dearth of FP resources, oncology providers may lack knowledge around FP. Thus, informational needs can be unmet, leading to anxiety and distress in patients. Provision of pertinent and timely information can help patients cope better with their diagnosis. FP pamphlets were developed for men and women with cancer. A cross-sectional in-house survey, using convenience sampling, evaluated the pamphlets' effectiveness and measured ease of understanding, acceptability, and perceived utility. Patients and partners were also asked to provide recommendations and complete the Short Test of Functional Health Literacy in Adults (S-TOFHLA) measuring health literacy level. This helps determine if health literacy influences perception of pamphlet effectiveness. All participants (n = 56) reviewed both pamphlets. Fifty-four participants (96 %) found the pamphlet for men useful, while 29 participants (52 %) improved their male fertility knowledge. The pamphlet for women was useful for 52 participants (93 %) and improved knowledge in 35 (63 %) of them. Although the majority of participants had adequate health literacy (98 %), there was insufficient sample diversity to determine if health literacy influenced the pamphlet's effectiveness. Participants indicated preference in receiving verbal (73 %) and written (66 %) information over watching videos or in-class education. They recommended including fertility clinics, financial resources, and statistics in the brochures. These FP pamphlets were concluded as effective in supporting patients in making FP decisions. PMID- 27671920 TI - SmartSIM - a virtual reality simulator for laparoscopy training using a generic physics engine. AB - Virtual reality (VR) training simulators have started playing a vital role in enhancing surgical skills, such as hand-eye coordination in laparoscopy, and practicing surgical scenarios that cannot be easily created using physical models. We describe a new VR simulator for basic training in laparoscopy, i.e. SmartSIM, which has been developed using a generic open-source physics engine called the simulation open framework architecture (SOFA). This paper describes the systems perspective of SmartSIM including design details of both hardware and software components, while highlighting the critical design decisions. Some of the distinguishing features of SmartSIM include: (i) an easy-to-fabricate custom built hardware interface; (ii) use of a generic physics engine to facilitate wider accessibility of our work and flexibility in terms of using various graphical modelling algorithms and their implementations; and (iii) an intelligent and smart evaluation mechanism that facilitates unsupervised and independent learning. PMID- 27671918 TI - Anxiety Disorders and Cardiovascular Disease. AB - Anxiety and its associated disorders are common in patients with cardiovascular disease and may significantly influence cardiac health. Anxiety disorders are associated with the onset and progression of cardiac disease, and in many instances have been linked to adverse cardiovascular outcomes, including mortality. Both physiologic (autonomic dysfunction, inflammation, endothelial dysfunction, changes in platelet aggregation) and health behavior mechanisms may help to explain the relationships between anxiety disorders and cardiovascular disease. Given the associations between anxiety disorders and poor cardiac health, the timely and accurate identification and treatment of these conditions is of the utmost importance. Fortunately, pharmacologic and psychotherapeutic interventions for the management of anxiety disorders are generally safe and effective. Further study is needed to determine whether interventions to treat anxiety disorders ultimately impact both psychiatric and cardiovascular health. PMID- 27671921 TI - Ataxia telangiectasia associated with nodular regenerative hyperplasia. PMID- 27671922 TI - Effects of planned, mistimed and unwanted pregnancies on the use of prenatal health services in sub-Saharan Africa: a multicountry analysis of Demographic and Health Survey data. AB - OBJECTIVES: We analysed the extent of planned, mistimed and unwanted pregnancies and how they predict optimal use of prenatal (timing and number of antenatal) care services in 30 African countries. METHODS: We pooled data from Demographic and Health Surveys conducted in 30 African countries between 2006 and 2015. We described the extent of mistimed and unwanted pregnancies and further used mixed effects logistic and Poisson regression estimation techniques to examine the impacts of planned, mistimed and unwanted pregnancies on the use of prenatal health services. RESULTS: In total, 73.65% of pregnancies in all countries were planned. Mistimed pregnancy ranged from 7.43% in Burkina Faso to 41.33% in Namibia. Unwanted pregnancies were most common in Swaziland (39.54%) and least common in Niger (0.74%). Timely (first trimester) initiation of ANC was 37% overall in all countries; the multicountry average number of ANC visits was optimal [4.1; 95% CI: 4.1-4.2] but with notable disparities between countries. Overall, mistimed and unwanted pregnancies were strongly associated with late ANC attendance and fewer visits women made in the pooled analysis. CONCLUSIONS: Unintended pregnancies are critical risks to achieving improved maternal health in respect of early and optimal ANC coverage for women in Africa. Programmes targeted at advancing coverage of ANC in Africa need to deploy contextually appropriate mechanisms to prevent unintended pregnancies. PMID- 27671924 TI - Copper-Catalyzed Vicinal Diphosphination of Styrenes: Access to 1,2 Bis(diphenylphosphino)ethane-Type Bidentate Ligands from Olefins. AB - A copper/N-heterocyclic carbene (NHC) catalyzed oxidative vicinal diphosphination of styrenes with diphenyl(trimethylsilyl)phosphine proceeds in the presence of LiOtBu and a pyridine N-oxide/MnO2 combined oxidant to deliver the corresponding 1,2-bis(diphenylphosphino)ethanes (DPPEs) in good yields. The present copper catalysis can provide access to the DPPE-type ligands directly from the relatively simple alkenes. PMID- 27671923 TI - Skellam process with resetting: a neural spike train model. AB - This paper introduces the Skellam process with resetting. Resetting is a modification that accommodates the modeling of neural spike trains. We show this as a biologically plausible model, which codes the information content of neural spike trains with three, potentially, time-varying functions. We show that the interspike interval distribution under this model follows a mixture of gamma distributions, a flexible class covering a wide range of commonly used models. Through simulation studies and the analyses of connected retinal ganglion and lateral geniculate nucleus cells, we evaluate the performance of this model. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27671925 TI - How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians. AB - OBJECTIVES: In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT. METHODS: Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician scientists working with children on the design of investigator-initiated PKPD studies. KEY FINDINGS: The importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose-ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose finding study. CONCLUSIONS: The emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing. PMID- 27671927 TI - Notch signaling in oral squamous neoplasia. AB - Notch signaling is involved in cell-cell communication. It is an evolutionarily ancient mechanism and plays a fundamental role in development. The typical function of Notch signaling is the regulation of cell fate segregation at asymmetric division; however, a role in tumorigenesis has also been suggested. Inactivating mutations of NOTCH1 are present in about 10 % of cases of squamous cell carcinoma of the skin, oral cavity, esophagus, and lung, rendering it one of the most frequently mutated genes in squamous cell carcinoma. Mouse knockout studies have demonstrated that Notch1 is imperative for early development but is dispensable for formation of the squamous epithelium. However, loss of Notch signaling predisposes the epidermis to hyperplasia and increases tumor incidence. This tumor-inducing effect resulting from the loss of Notch signaling is associated with non-cell-autonomous effects that are elicited by subtle alteration of epithelial cell features, generating a wound-like microenvironment in the underlying stroma. We found that Notch1 was expressed specifically in the basal cells of the oral squamous epithelium. In cancer and oral epithelial dysplasia, it was significantly downregulated, suggesting that reduced Notch activity plays a distinct role in oral neoplasia. PMID- 27671926 TI - A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population. AB - Leigh disease is a progressive, infantile-onset, neurodegenerative disorder characterized by feeding difficulties, failure to thrive, hypotonia, seizures, and central respiratory compromise. Metabolic and neuroimaging investigations typically identify abnormalities consistent with a disorder of mitochondrial energy metabolism. Mutations in more than 35 genes affecting the mitochondrial respiratory chain encoded from both the nuclear and mitochondrial genomes have been associated with Leigh disease. The clinical presentations of five individuals of Hutterite descent with Leigh disease are described herein. An identity-by-descent mapping and candidate gene approach was used to identify a novel homozygous c.393dupA frameshift mutation in the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (NDUFS4) gene. The carrier frequency of this mutation was estimated in >1,300 Hutterite individuals to be 1 in 27. (c) 2017 Wiley Periodicals, Inc. PMID- 27671928 TI - A Guide to Using STITCHER for Overlapping Assembly PCR Applications. AB - Overlapping PCR is commonly used in many molecular applications that include stitching PCR fragments together, generating fluorescent transcriptional and translational fusions, inserting mutations, making deletions, and PCR cloning. Overlapping PCR is also used for genotyping and in detection experiments using techniques such as loop-mediated isothermal amplification (LAMP). STITCHER is a web tool providing a central resource for researchers conducting all types of overlapping assembly PCR experiments with an intuitive interface for automated primer design that's fast, easy to use, and freely available online. PMID- 27671929 TI - Synthetic Gene Design Using Codon Optimization On-Line (COOL). AB - Codon optimization has been widely used for designing native or synthetic genes to enhance their expression in heterologous host organisms. We recently developed Codon Optimization On-Line (COOL) which is a web-based tool to provide multi objective codon optimization functionality for synthetic gene design. COOL provides a simple and flexible interface for customizing codon optimization based on several design parameters such as individual codon usage, codon pairing, and codon adaptation index. User-defined sequences can also be compared against the COOL optimized ones to show the extent by which the user's sequences can be evaluated and further improved. The utility of COOL is demonstrated via a case study where the codon optimized sequence of an invertase enzyme is generated for the enhanced expression in E. coli. PMID- 27671930 TI - Shuffle Optimizer: A Program to Optimize DNA Shuffling for Protein Engineering. AB - DNA shuffling is a powerful tool to develop libraries of variants for protein engineering. Here, we present a protocol to use our freely available and easy-to use computer program, Shuffle Optimizer. Shuffle Optimizer is written in the Python computer language and increases the nucleotide homology between two pieces of DNA desired to be shuffled together without changing the amino acid sequence. In addition we also include sections on optimal primer design for DNA shuffling and library construction, a small-volume ultrasonicator method to create sheared DNA, and finally a method to reassemble the sheared fragments and recover and clone the library. The Shuffle Optimizer program and these protocols will be useful to anyone desiring to perform any of the nucleotide homology-dependent shuffling methods. PMID- 27671931 TI - Simple Cloning by Prolonged Overlap Extension-PCR with Application to the Preparation of Large-Size Random Gene Mutagenesis Library in Escherichia coli. AB - We developed a simple method (simple cloning) for subcloning DNA fragments into any location of a targeted vector without the need of restriction enzyme, ligase, exonuclease, or recombinase in Escherichia coli. This technology can be applied to common E. coli hosts (e.g., DH5alpha, JM109, TOP10, BL21(DE3)). The protocol includes three steps: (1) generate DNA insert and linear vector backbone by regular high-fidelity PCR, where these two DNA fragments contain 3' and 5' overlapping termini; (2) generate DNA multimers based on these two DNA fragments by using prolonged overlap extension-PCR (POE-PCR) without primers added; and (3) transform POE-PCR product to competent Escherichia coli cells directly, yielding the desired plasmid. Simple cloning provides a new cloning method with great simplicity and flexibility. Furthermore, this new method can be modified for the preparation of a large-size mutant library for directed evolution in E. coli. Using this method, it is very easy to generate a mutant library with a size of more than 10(7) per 50 MUL of the POE-PCR product within 1 day. PMID- 27671932 TI - SpeedyGenes: Exploiting an Improved Gene Synthesis Method for the Efficient Production of Synthetic Protein Libraries for Directed Evolution. AB - Gene synthesis is a fundamental technology underpinning much research in the life sciences. In particular, synthetic biology and biotechnology utilize gene synthesis to assemble any desired DNA sequence, which can then be incorporated into novel parts and pathways. Here, we describe SpeedyGenes, a gene synthesis method that can assemble DNA sequences with greater fidelity (fewer errors) than existing methods, but that can also be used to encode extensive, statistically designed sequence variation at any position in the sequence to create diverse (but accurate) variant libraries. We summarize the integrated use of GeneGenie to design DNA and oligonucleotide sequences, followed by the procedure for assembling these accurately and efficiently using SpeedyGenes. PMID- 27671933 TI - BASIC: A Simple and Accurate Modular DNA Assembly Method. AB - Biopart Assembly Standard for Idempotent Cloning (BASIC) is a simple, accurate, and robust DNA assembly method. The method is based on linker-mediated DNA assembly and provides highly accurate DNA assembly with 99 % correct assemblies for four parts and 90 % correct assemblies for seven parts [1]. The BASIC standard defines a single entry vector for all parts flanked by the same prefix and suffix sequences and its idempotent nature means that the assembled construct is returned in the same format. Once a part has been adapted into the BASIC format it can be placed at any position within a BASIC assembly without the need for reformatting. This allows laboratories to grow comprehensive and universal part libraries and to share them efficiently. The modularity within the BASIC framework is further extended by the possibility of encoding ribosomal binding sites (RBS) and peptide linker sequences directly on the linkers used for assembly. This makes BASIC a highly versatile library construction method for combinatorial part assembly including the construction of promoter, RBS, gene variant, and protein-tag libraries. In comparison with other DNA assembly standards and methods, BASIC offers a simple robust protocol; it relies on a single entry vector, provides for easy hierarchical assembly, and is highly accurate for up to seven parts per assembly round [2]. PMID- 27671934 TI - Enzymatic Synthesis of Single-Stranded Clonal Pure Oligonucleotides. AB - Single-stranded oligonucleotides, or oligodeoxyribonucleotides (ODNs), are very important in several fields of science such as molecular biology, diagnostics, nanotechnology, and gene therapy. They are usually chemically synthesized. Here we describe an enzymatic method which enables us to synthesize pure oligonucleotides which can be up to several hundred long bases. PMID- 27671935 TI - Rapid Assembly of DNA via Ligase Cycling Reaction (LCR). AB - The assembly of multiple DNA parts into a larger DNA construct is a requirement in most synthetic biology laboratories. Here we describe a method for the efficient, high-throughput, assembly of DNA utilizing the ligase chain reaction (LCR). The LCR method utilizes non-overlapping DNA parts that are ligated together with the guidance of bridging oligos. Using this method, we have successfully assembled up to 20 DNA parts in a single reaction or DNA constructs up to 26 kb in size. PMID- 27671936 TI - PaperClip: A Simple Method for Flexible Multi-Part DNA Assembly. AB - Joining DNA sequences to create linear and circular constructs is a basic requirement in molecular biology. Here we describe PaperClip, a recently developed method, which enables assembly of multiple DNA sequences in one reaction in a combinatorial manner. In contrast to other homology-based multi part assembly methods currently available, PaperClip allows assembly of a given set of parts in any order without requiring specific single-use oligonucleotides for each assembly order. PMID- 27671937 TI - The Polymerase Step Reaction (PSR) Method for Gene and Library Synthesis. AB - Current gene synthesis methods often incorporate a PCR-amplifying step in order to yield sufficient final product that is detectable and resolvable from multiple off-products. This amplification step can cause stochastic sampling effects that propagate errors during the synthesis and lower the variability when applied towards the construction of randomized libraries. We present the method for polymerase step reaction (PSR), a simple DNA polymerase-based gene synthesis reaction that assembles DNA oligonucleotides in a unidirectional fashion without the need for a PCR-type amplification (Lee et al., BioTechniques 59:163-166, 2015). The PSR method is simple and efficient with little off-product production, undetected stochastic sampling effects, and maximized variability when used to synthesize phage display libraries. PMID- 27671938 TI - Clonetegration Using OSIP Plasmids: One-Step DNA Assembly and Site-Specific Genomic Integration in Bacteria. AB - Clonetegration is a method for site-specific insertion of DNA into prokaryotic chromosomes, based on bacteriophage integrases. The method combines DNA cloning/assembly and chromosomal integration into a single step, providing a simple and rapid strategy for inserting DNA sequences into bacterial chromosomes. PMID- 27671939 TI - Generation of DNA Constructs Using the Golden GATEway Cloning Method. AB - One of the most frequently executed tasks for molecular biologists is the design and generation of complex DNA constructs. Recently, we established the Golden GATEway cloning kit for the fast and efficient generation of transgenesis vectors. This cloning kit allows the modular assembly of DNA fragments in a defined order. The modularity reflects how complex transgenesis constructs are set up. For example, genome modification tools such as the Cre-Lox system utilize small recombination elements that are combined with larger open reading frames and noncoding regulatory DNA. Another example is that proteinogenic genes can be extended with different localisation tags or fluorescent markers. The Golden GATEway cloning kit allows focusing on the design of a transgenesis construct without having to compromise it by so far available cloning strategies. Here, we provide a step-by-step introduction on how to use the Golden GATEway cloning kit. PMID- 27671940 TI - Gene Deletion by Synthesis in Yeast. AB - Targeted gene deletion is a useful tool for understanding the function of a gene and its protein product. We have developed an efficient and robust gene deletion approach in yeast that employs oligonucleotide-based gene synthesis. This approach requires a deletion cassette composed of three modules: a central 1397 bp KanMX4 selection marker module and two 366-bp gene-specific flanking modules. The invariable KanMX4 module can be used in combination with different pairs of flanking modules targeting different genes. The two flanking modules consist of both sequences unique to each cassette (chromosomal homologous regions and barcodes) and those common to all deletion constructs (artificial linkers and restriction enzyme sites). Oligonucleotides for each module and junction regions are designed using the BatchBlock2Oligo program and are synthesized on a 96-well basis. The oligonucleotides are ligated into a single deletion cassette by ligase chain reaction, which is then amplified through two rounds of nested PCR to obtain sufficient quantities for yeast transformation. After removal of the artificial linkers, the deletion cassettes are transformed into wild-type diploid fission yeast SP286 cells. Verification of correct clone and gene deletion is achieved by performing check PCR and tetrad analysis. This method with proven effectiveness, as evidenced by a high success rate of gene deletion, can be potentially applicable to create systematic gene deletion libraries in a variety of yeast species. PMID- 27671941 TI - Efficient Assembly of DNA Using Yeast Homologous Recombination (YHR). AB - The assembly of multiple DNA parts into a larger DNA construct is a requirement in most synthetic biology laboratories. Here we describe a method for the efficient, high-throughput, assembly of DNA utilizing the yeast homologous recombination (YHR). The YHR method utilizes overlapping DNA parts that are assembled together by Saccharomyces cerevisiae via homologous recombination between designed overlapping regions. Using this method, we have successfully assembled up to 12 DNA parts in a single reaction. PMID- 27671942 TI - Simultaneous Removal of Multiple DNA Segments by Polymerase Chain Reactions. AB - Precise DNA manipulation is a key enabling technology for synthetic biology. Approaches based on restriction digestion are often limited by the presence of certain restriction enzyme recognition sites. Recent development of restriction free cloning approaches has greatly enhanced the flexibility and speed of molecular cloning. Most restriction-free cloning methods focus on DNA assembly. Much less work has been dedicated towards DNA removal. Here we introduce a protocol that allows simultaneous removal of multiple DNA segments from a plasmid using polymerase chain reactions (PCR). Our approach will be beneficial to applications in multiple sites mutagenesis, DNA library construction, genetic and protein engineering, and synthetic biology. PMID- 27671943 TI - Rapid Construction of Recombinant Plasmids by QuickStep-Cloning. AB - QuickStep-Cloning is a novel molecular cloning technique that builds upon the concepts of asymmetric PCR and megaprimer-based amplification of whole plasmid. It was designed specifically to address the major drawbacks of previously reported cloning methods. The fully optimized protocol allows for a seamless integration of a long DNA fragment into any position within a plasmid of choice, in a time-efficient and cost-effective manner, without the need of a tedious DNA gel purification, a restriction digestion, and an enzymatic ligation. QuickStep Cloning can be completed in less than 6 h, significantly faster than most of the existing cloning methods, while retaining high efficiency. PMID- 27671944 TI - Immobilized MutS-Mediated Error Removal of Microchip-Synthesized DNA. AB - Applications of microchip-synthesized oligonucleotides for de novo gene synthesis are limited primarily by their high error rates. The mismatch binding protein MutS, which can specifically recognize and bind to mismatches, is one of the cheapest tools for error correction of synthetic DNA. Here, we describe a protocol for removing errors in microchip-synthesized oligonucleotides and for the assembly of DNA segments using these oligonucleotides. This protocol can also be used in traditional de novo gene DNA synthesis. PMID- 27671945 TI - Selection of Error-Less Synthetic Genes in Yeast. AB - Conventional gene synthesis is usually accompanied by sequence errors, which are often deletions derived from chemically synthesized oligonucleotides. Such deletions lead to frame shifts and mostly result in premature translational terminations. Therefore, in-frame fusion of a marker gene to the downstream of a synthetic gene is an effective strategy to select for frame-shift-free synthetic genes. Functional expression of fused marker genes indicates that synthetic genes are translated without premature termination, i.e., error-less synthetic genes. A recently developed nonhomologous end joining (NHEJ)-mediated DNA cloning method in the yeast Kluyveromyces marxianus is suitable for the selection of frame-shift free synthetic genes. Transformation and NHEJ-mediated in-frame joining of a synthetic gene with a selection marker gene enables colony formation of only the yeast cells containing synthetic genes without premature termination. This method increased selection frequency of error-less synthetic genes by 3- to 12-fold. PMID- 27671946 TI - Injectable and Pathogen-Mimicking Hydrogels for Enhanced Protective Immunity against Emerging and Highly Pathogenic Influenza Virus. AB - Seasonal emerging infectious diseases such as influenza A impose substantial risk and need new translational strategies to achieve active immunomodulation. Here, a novel injectable pathogen-mimicking hydrogel (iPMH) that can enhance both cellular and humoral immune responses is suggested. By the help of poly(gamma glutamic acid) that has abundant carboxylate groups and dispersion helper function, hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl lipid A (MPLA) molecules and viral antigens (PR8, W150) can be successfully combined as pathogen-mimicking adjuvants. Polyelectrolyte complex between the poly(gamma glutamic acid)-based adjuvants and collagens generate in situ gel-forming hydrogel at physiological temperature. When the iPMH are immunized, they act as a pathogen-mimicking (MPLA, H1N1, H5N1) immune priming center and a depot for continuous stimulation of immune system, resulting in the induction of high levels (8.5 times higher) of antigen-specific IgG titers in the sera of mice and the increased number of IFN-gamma-producing cells (7.3 times higher) compared with those in the groups immunized with antigen plus clinically used aluminum gels. Following the intranasal infection of the mouse adapted virus (emerging infectious 2009 H1N1 and highly pathogenic 2006 H5N1) at 50 times the 50% lethal dose, the mice immunized with viral antigens plus iPMH exhibit 100% protective immunity against lethal virus challenge. PMID- 27671947 TI - Febrile syndrome of unknown origin: Indications for 18F-FDG PET/CT in inflammatory and infectious processes. AB - Fever of unknown origin is defined as a body temperature greater than 38.3 degrees C lasting more than three weeks for which the cause could not be found within one week of hospital admission. More than 200 causes have been reported, and these can be classified into four categories: infections, inflammatory diseases, oncologic processes, and miscellaneous conditions. Noninvasive diagnostic techniques are used in 69.2% of cases and invasive techniques in 30.8%. Structural imaging techniques show the morphological changes from infectious, inflammatory, and tumor-related processes, but they do not allow the detection of the early changes brought about by these processes. The metabolic information provided by 18F-FDG PET/CT has a promising role in these patients. 18F-FDG uptake is based on the cells' use of glucose as a source of energy, so it can be observed in infectious, inflammatory, and tumor-related processes. The established non-oncologic indications for 18F-FDG PET/CT are sarcoidosis, osteomyelitis, spondylodiscitis, fever of unknown origin, and vasculitis, which together account for more than 85% of studies. PMID- 27671948 TI - A Bayesian approach to fiber orientation estimation guided by volumetric tract segmentation. AB - Diffusion magnetic resonance imaging (dMRI) provides information about the microstructure of white matter in the human brain. From dMRI, streamlining tractography is often used to reconstruct computational representations of white matter tracts from which differences in structural connectivity can be explored. In the fiber tracking process, anatomical information can help reduce tracking errors caused by crossing fibers and image noise. In this paper, we propose a Bayesian method for estimating fiber orientations (FOs) guided by anatomical tract information using diffusion tensor imaging (DTI), which is a standard clinical and research dMRI protocol. The proposed method is named Fiber Orientation Reconstruction guided by Tract Segmentation (FORTS). A first step segments and labels the white matter tracts volumetrically, including explicit representations of crossing regions. A second step estimates the FOs using the diffusion information and the anatomical knowledge from segmented white matter tracts. A single FO is estimated in the noncrossing regions while two FOs are estimated in the crossing regions. A third step carries out streamlining tractography that uses information from both the segmented tracts and the estimated FOs. Experiments performed on a digital crossing phantom, a physical phantom, and brain DTI of 18 healthy subjects show that FORTS is able to use the anatomical information to produce FOs with better accuracy and to reduce anatomically incorrect streamlines. In particular, on the brain DTI data, we studied the connectivity of anatomically defined tracts to cortical areas, which is not straightforwardly achievable using only volumetric tract segmentation. These connectivity results demonstrate the potential application of FORTS to scientific studies. PMID- 27671949 TI - Automatic coronary artery segmentation based on multi-domains remapping and quantile regression in angiographies. AB - Coronary artery disease has become the most dangerous diseases to human life. And coronary artery segmentation is the basis of computer aided diagnosis and analysis. Existing segmentation methods are difficult to handle the complex vascular texture due to the projective nature in conventional coronary angiography. Due to large amount of data and complex vascular shapes, any manual annotation has become increasingly unrealistic. A fully automatic segmentation method is necessary in clinic practice. In this work, we study a method based on reliable boundaries via multi-domains remapping and robust discrepancy correction via distance balance and quantile regression for automatic coronary artery segmentation of angiography images. The proposed method can not only segment overlapping vascular structures robustly, but also achieve good performance in low contrast regions. The effectiveness of our approach is demonstrated on a variety of coronary blood vessels compared with the existing methods. The overall segmentation performances si, fnvf, fvpf and tpvf were 95.135%, 3.733%, 6.113%, 96.268%, respectively. PMID- 27671950 TI - "Mouth Wide Shut": Strategies of Female Sex Workers for Coping With Intimate Partner Violence. AB - The aim of this study was to explore the relationship between possible violence suffered by female sex workers in their intimate relationships, with their affects, coping strategies, and emotional regulation to overcome such violence and improve their well-being. Structured personal interviews were carried out with female sex workers in three different settings: street, club, and flats. The sample was composed of 137 Spanish female sex workers (85.4% are foreign and 20% Spanish-born sex workers). High levels of tension and problems with their partners were linked to an affective imbalance and poor well-being. Positive affectivity determined the use of adaptive strategies, whereas negative affectivity predicted dysfunctional strategies. Three different path analyses and theoretical support concluded that self-control was the only strategy related to improve well-being in female sex workers who reported lower potential tension and difficulty in their intimate relationships. In contrast, inhibition was associated with an increase on distress levels when negative affectivity predominated and sex workers had reported potential tension and difficulty situations with their partners. It was a cross-sectional study, and thus we cannot infer causality or direction from the observed associations. Given these findings, violence prevention strategies in the intimate relationships should be prioritized in the prostitution context. PMID- 27671951 TI - Predicting the Effects of Sexual Assault Research Participation: Reactions, Perceived Insight, and Help-Seeking. AB - This study examined effects of participating in survey research for women sexual assault survivors with other trauma histories to understand the role of study participation on perceived insight and long-term help-seeking behaviors. A diverse sample of 1,863 women from a large Midwestern city participated in a 3 year study on women's experiences with sexual assault. Regression analyses were conducted to (a) examine predictors of immediate positive and negative reactions to survey participation and (b) assess the impact of the survey on perceived insight and women's long-term help-seeking behavior. Overall, most women in the study had a higher positive than negative reaction to the survey (92%), with a significant proportion indicating they sought additional services as a result of participation (55%). Women with child sexual abuse (CSA), more emotion dysregulation, and more characterological self-blame had more negative reactions to the survey, whereas those with more education and individual adaptive coping had more positive reactions. Women who said they gained insight from answering survey questions were most likely to seek additional help. This study extends the literature by examining cumulative trauma and postassault symptoms in relation to the effects of survey participation. This is also the first study of women sexual assault survivors to find a relationship between gaining perceived insight from research and subsequent help-seeking. Participating in sexual assault research may help survivors gain greater insight into their recovery, which can lead them to seek out more resources for their ongoing trauma-related problems. PMID- 27671952 TI - Utilizing a General Strain Framework to Examine Behavioral Responses to Psychological Intimate Partner Violence: Are Responses Gendered? AB - We know from the violence literature that a distinct sex disparity exists in the perpetration of other-directed violence (ODV). Some scholars suggest that this disparity is explained in part by gendered reactions to stress, strain, or violence victimization, in which males and females engage in different coping mechanisms, with males more likely to engage in ODV than females. Using a college sample, we investigate the behavioral responses of male and female victims of psychological intimate partner abuse. We find that although there is a sex disparity in the use of ODV as a coping mechanism, there is also a distinct gender orientation disparity. Our results indicate that victims who ascribe to a masculine identity are more likely than those of a feminine identity to engage in ODV, regardless of biological sex. These findings shed light on the impact of gender orientation as both a risk and protective factor in the use of ODV. PMID- 27671953 TI - The Barber Pole Might Have Been an Early Sign for Patient-Centered Care: What Do Interprofessional Education and Interprofessional Collaborative Practice Look Like Now? AB - In 2009, the Interprofessional Education Collaborative (IPEC) was initiated. Its release of interprofessional collaborative practice (ICP) core competencies in 2011 was pivotal for the engagement of health care professionals, including dentistry; in patient-centered, collaborative efforts for interprofessional education (IPE); and ICP. Thereby, IPEC is helping to put into application, in North America, the 2010 World Health Organization (WHO) Framework for Action on Interprofessional Education and Collaborative Practice. This article introduces IPE/ICP in 5 phases of evolution, emphasizing dental influence and inclusion, from historical perspectives through current applications that are expanded on in the accompanying articles elsewhere in this issue. PMID- 27671954 TI - Interprofessional Collaborative Practice Models in Chronic Disease Management. AB - Interprofessional collaboration in health has become essential to providing high quality care, decreased costs, and improved outcomes. Patient-centered care requires synthesis of all the components of primary and specialty medicine to address patient needs. For individuals living with chronic diseases, this model is even more critical to obtain better health outcomes. Studies have shown shown that oral health and systemic disease are correlated as it relates to disease development and progression. Thus, inclusion of oral health in many of the existing and new collaborative models could result in better management of chronic illnesses and improve overall health outcomes. PMID- 27671955 TI - Problems and Solutions for Interprofessional Education in North American Dental Schools. AB - Interprofessional education (IPE) is a relatively new part of dental education. Its implementation is mandated by accreditation standards, but it is also essential to good patient care. Diverse dental schools from various regions of North America outline problems they have faced in IPE and the solutions that they have found to surmount these problems. Commonalities and unique features of these problems and solutions are discussed. PMID- 27671956 TI - Interprofessional Education for the Dentist in Managing Acute and Chronic Pain. AB - Dental education is at the intersection of affordable health care, opioid-abuse crisis, and collaborative practice benefits. Students must engage in interprofessional education (IPE) for pain management. Graduates must recognize appropriate management of acute dental pain and understand the dentist's role in interprofessional treatment of chronic disease, including management of temporomandibular disorders and orofacial neuropathic pain, chronic pain in general, and the consideration of opioids. This article reviews accreditation standards, compares these standards with recommendations from the International Association for the Study of Pain and regulatory boards, and presents examples of enhanced pain education. PMID- 27671957 TI - Interprofessional Collaboration in Improving Oral Health for Special Populations. AB - People with complex medical, physical, and psychological conditions are among the most underserved groups in receiving dental care and consequently have the most significant oral health disparities of any group. The traditional dental care delivery system is not able to deliver adequate services to these people with "special needs" for a variety of reasons. New systems of care are evolving that better serve the needs of these groups by using interprofessional teams to reach these individuals and integrate oral health services into social, educational, and general health systems. PMID- 27671958 TI - Interprofessional Collaborative Practice: An Oral Health Paradigm for Women. AB - Interprofessional collaborative practice (IPC) is paramount to the future of oral health education. As such, it is critical that today's health care education continues to expand its curriculum to promote oral health as an essential component in the IPC approach to women's health. This article explores models that can be implemented using an IPC framework to foster better approaches in the delivery of care to female patients. PMID- 27671959 TI - Oral Health and Interprofessional Collaborative Practice: Examples of the Team Approach to Geriatric Care. AB - Oral health for the older adult patient is vital for function, comfort, and communication and is a critical component of overall health. Oral diseases such as dental caries, periodontal disease, and oral cancer may lead to pain, functional limitations, and decreased quality of life. Optimal oral health outcomes are often owing to effective interprofessional collaboration between and among health care providers, in conjunction with patient family members and caregivers. This article highlights 2 cases illustrating how interprofessional team dynamics can affect patient outcomes. PMID- 27671960 TI - Addressing Health Disparities via Coordination of Care and Interprofessional Education: Lesbian, Gay, Bisexual, and Transgender Health and Oral Health Care. AB - Lesbian, gay, bisexual, and transgender (LGBT) persons are a diverse group, but they share a common need for competent, accessible health care, dispensed without intolerance and with an understanding of their unique health needs. Dental practitioners need to understanding that LGBT persons have distinctive health (and oral health) needs. This article reviews the literature on oral and overall health of LGBT persons in the United States, and discusses ways in which dentists can improve the health care they provide to this vulnerable population, including how interprofessional education and collaborative practice may help to reduce oral health disparities within this group. PMID- 27671962 TI - Policy Development Fosters Collaborative Practice: The Example of the Minamata Convention on Mercury. AB - This article provides an example of interprofessional collaboration for policy development regarding environmental global health vis-a-vis the Minamata Convention on Mercury. It presents an overview of mercury and mercury-related environmental health issues; public policy processes and stakeholders; and specifics including organized dentistry's efforts to create global policy to restrict environmental contamination by mercury. Dentistry must participate in interprofessional collaborations and build on such experiences to be optimally placed for ongoing interprofessional policy development. Current areas requiring dental engagement for interprofessional policy development include education, disaster response, HPV vaccination, pain management, research priorities, and antibiotic resistance. PMID- 27671961 TI - The Evolving Role of Dental Responders on Interprofessional Emergency Response Teams. AB - Disaster and pandemic response events require an interprofessional team of health care responders to organize and work together in high-pressure, time-critical situations. Civilian oral health care professionals have traditionally been limited to forensic identification of human remains. However, after the bombing of the Twin Towers in New York, federal agencies realized that dentists can play significant roles in disaster and immunization response, especially on interprofessional responder teams. Several states have begun to incorporate dentists into the first responder community. This article discusses the roles of dental responders and highlights legislative advancements and advocacy efforts supporting the dental responder. PMID- 27671963 TI - Genetics: The Future Is Now with Interprofessional Collaboration. AB - With the growing complexity of health care, interprofessional communication and collaboration are essential to optimize the care of dental patients, including consideration of genetics. A dental case exemplifies the challenges and benefits of an interprofessional approach to managing pediatric patients with oligodontia and a family history of colon cancer. The interprofessional team includes dental, genetic, nutritional, and surgical experts. PMID- 27671964 TI - Integrating Oral Health and Primary Care: Federal Initiatives to Drive Systems Change. AB - This article describes federal programs, initiatives, and partnerships that have the demonstrated potential to initiate and institutionalize interprofessional practice that includes oral health providers as integral to the provider team. A discussion of landmark documents and reports, the role of legislation and statutory authority, and the influence of federal program priorities towards a national movement to increase access to care to bridge the chasms between the medical health care system, dental delivery system, and oral health is presented. PMID- 27671965 TI - The Alphabet Soup of Interprofessional Education and Collaborative Practice Acronyms with Dental Seasoning. PMID- 27671967 TI - The battlefield in the war against attaching-and-effacing bacterial pathogens: Monocytes, macrophages and dendritic cells in action. AB - The recent adoption of a unified nomenclature for the mononuclear phagocyte system has already led to the generation of novel strategies for specifically depleting a single subset of phagocytes in the presence of intact lymphoid structures. Herein, we provide a detailed description of how the various types of tissue phagocyte orchestrate the host's defense against enteric bacterial infections. From a bench-to-bedside perspective, we expect that this paradigm will accelerate the development of novel adjuvants and vaccines in human and veterinary microbiology. PMID- 27671968 TI - Sexual Satisfaction and the Importance of Sexual Health to Quality of Life Throughout the Life Course of U.S. Adults. AB - INTRODUCTION: Discussions about sexual health are uncommon in clinical encounters, despite the sexual dysfunction associated with many common health conditions. Understanding of the importance of sexual health and sexual satisfaction in U.S. adults is limited. AIM: To provide epidemiologic data on the importance of sexual health for quality of life and people's satisfaction with their sex lives and to examine how each is associated with demographic and health factors. METHODS: Data are from a cross-sectional self-report questionnaire from a sample of 3,515 English-speaking U.S. adults recruited from an online panel that uses address-based probability sampling. MAIN OUTCOME MEASURES: We report ratings of importance of sexual health to quality of life (single item with five point response) and the Patient-Reported Outcomes Measurement Information System Satisfaction With Sex Life score (five items, each with five-point responses, scores centered on the U.S. mean). RESULTS: High importance of sexual health to quality of life was reported by 62.2% of men (95% CI = 59.4-65.0) and 42.8% of women (95% CI = 39.6-46.1, P < .001). Importance of sexual health varied by sex, age, sexual activity status, and general self-rated health. For the 55% of men and 45% of women who reported sexual activity in the previous 30 days, satisfaction with sex life differed by sex, age, race-ethnicity (among men only), and health. Men and women in excellent health had significantly higher satisfaction than participants in fair or poor health. Women with hypertension reported significantly lower satisfaction (especially younger women), as did men with depression or anxiety (especially younger men). CONCLUSION: In this large study of U.S. adults' ratings of the importance of sexual health and satisfaction with sex life, sexual health was a highly important aspect of quality of life for many participants, including participants in poor health. Moreover, participants in poorer health reported lower sexual satisfaction. Accordingly, sexual health should be a routine part of clinicians' assessments of their patients. Health care systems that state a commitment to improving patients' overall health must have resources in place to address sexual concerns. These resources should be available for all patients across the lifespan. PMID- 27671966 TI - Phosphatidic acid and neurotransmission. AB - Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system. PMID- 27671969 TI - Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol. AB - INTRODUCTION: One of the most serious known adverse effects of feminizing cross sex hormone therapy (CSHT) is venous thromboembolism (VTE); however, no study has assessed the incidence of VTE from the hormone therapies used in the United States because previous publications on this topic have originated in Europe. CSHT in the United States typically includes estradiol with the antiandrogen spironolactone, whereas in Europe estradiol is prescribed with the progestin cyproterone acetate. AIM: To estimate the incidence of VTE from the standard feminizing CSHTs used in the United States. METHODS: A retrospective chart review of transgender women who had been prescribed oral estradiol at a District of Columbia community health center was performed. MAIN OUTCOME MEASURE: The primary outcomes of interest were deep vein thrombosis or pulmonary emboli. RESULTS: From January 1, 2008 through March 31, 2016, 676 transgender women received oral estradiol-based CSHT for a total of 1,286 years of hormone treatment and a mean of 1.9 years of CSHT per patient. Only one individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10,000 person years. CONCLUSION: There was a low incidence of VTE in this population of transgender women receiving oral estradiol. PMID- 27671971 TI - Effect of glycation inhibitors on aging and age-related diseases. AB - Vast evidence supports the view that glycation of proteins is one of the main factors contributing to aging and is an important element of etiopathology of age related diseases, especially type 2 diabetes mellitus, cataract and neurodegenerative diseases. Counteracting glycation can therefore be a means of increasing both the lifespan and healthspan. In this review, accumulation of glycation products during aging is presented, pathophysiological effects of glycation are discussed and ways of attenuation of the effects of glycation are described, concentrating on prevention of glycation. The effects of glycation and glycation inhibitors on the course of selected age-related diseases, such as Alzheimer's disease, Parkinson's disease and cataract are also reviewed. PMID- 27671970 TI - IMI - oral biopharmaceutics tools project - evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds. AB - Predicting oral bioavailability (Foral) is of importance for estimating systemic exposure of orally administered drugs. Physiologically-based pharmacokinetic (PBPK) modelling and simulation have been applied extensively in biopharmaceutics recently. The Oral Biopharmaceutical Tools (OrBiTo) project (Innovative Medicines Initiative) aims to develop and improve upon biopharmaceutical tools, including PBPK absorption models. A large-scale evaluation of PBPK models may be considered the first step. Here we characterise the OrBiTo active pharmaceutical ingredient (API) database for use in a large-scale simulation study. The OrBiTo database comprised 83 APIs and 1475 study arms. The database displayed a median logP of 3.60 (2.40-4.58), human blood-to-plasma ratio of 0.62 (0.57-0.71), and fraction unbound in plasma of 0.05 (0.01-0.17). The database mainly consisted of basic compounds (48.19%) and Biopharmaceutics Classification System class II compounds (55.81%). Median human intravenous clearance was 16.9L/h (interquartile range: 11.6-43.6L/h; n=23), volume of distribution was 80.8L (54.5-239L; n=23). The majority of oral formulations were immediate release (IR: 87.6%). Human Foral displayed a median of 0.415 (0.203-0.724; n=22) for IR formulations. The OrBiTo database was found to be largely representative of previously published datasets. 43 of the APIs were found to satisfy the minimum inclusion criteria for the simulation exercise, and many of these have significant gaps of other key parameters, which could potentially impact the interpretability of the simulation outcome. However, the OrBiTo simulation exercise represents a unique opportunity to perform a large-scale evaluation of the PBPK approach to predicting oral biopharmaceutics. PMID- 27671973 TI - Fire on cruise ships - A response to previous correspondence. PMID- 27671972 TI - Predictors of MERS-CoV infection: A large case control study of patients presenting with ILI at a MERS-CoV referral hospital in Saudi Arabia. AB - BACKGROUND: A case control study to better characterize the clinical features, laboratory, and radiological abnormalities associated with MERS-CoV infection in order to help with early identification of this syndrome from other respiratory infections. METHODS: Eighty patients admitted to a hospital in Riyadh, diagnosed with MERS-CoV infection based on RT-PCR were matched on age, sex, and the presence of a co-morbid condition on a basis of 1:2 to other patients admitted with respiratory symptoms and tested negative for MERS-CoV on RT-PCR. RESULTS: None of the reported MERS-CoV presenting symptoms was significantly associated with being infected with MERS-CoV. On the other hand, WBC count was significantly lower in patients with confirmed MERS-CoV infection (median 5.7 vs 9.3, P: 0.0004). Neutrophil count was as well significantly lower in MERS-CoV patients (median 3.7 vs 6.7, P: 0.0001). Both AST, and ALT values were significantly higher in MERS-CoV infected group (AST median 42 vs 36, P: 0.03, and ALT median 33 vs 28, P: 0.003). Overall our MERS-CoV mortality rate was (10%) below the national figure of (40%). CONCLUSIONS: None of the presenting symptoms are specific for MERS-CoV infection. And out of all the investigations WBC, neutrophil counts, AST and ALT values have some predictive utility. PMID- 27671974 TI - Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. METHODS: Patients were randomized to placebo, macitentan 3 mg, or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline, at month 6 and month 12, and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed. RESULTS: At month 6, macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio [HR], 0.60; 95% CI, 0.47-0.76; P < .0001) and MCS scores (HR, 0.76; 95% CI, 0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score. CONCLUSIONS: Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00660179; URL: clinicaltrials.gov. PMID- 27671975 TI - Effects of preparatory and action planning instructions on situation-specific and general fruit and snack intake. AB - Evidence to date suggests heterogeneity in the effects of implementation intentions on health behaviour, including diet. Additional variables and study designs may impact on their effectiveness. Preparatory action, such as making sure fruits are available for consumption, may be an important additional variable. Likewise, most implementation intention research has focused on changes in general intake, yet implementation intention instructions typically require participants to consider behaviour in specific situations. Little is known on how implementation intentions impact situation-specific intake. The present study sought to add to the evidence base by comparing (1) the effects of action planning instructions versus preparatory planning instructions on (2) both situation-specific (as formulated in the implementation intention instruction) and general intake of fruits and in-between meal snack intake frequency. Fruit intake was assessed in average pieces per day, whereas snacking intake was assessed as average frequency in days per week. Using non-probability sampling, 243 undergraduate students who intended to have a healthy diet were randomized to either a standard information control condition, an action planning condition, or a preparatory planning condition. Planning manipulations were based on previous work. Two weeks later, general and situation-specific intake was assessed again in 181 participants. Data were analysed using 2 (time) x 3 (conditions) analyses of variance. Results showed that both planning manipulations were successful in decreasing snack intake frequency in the specified situation, with larger effect sizes for the action planning condition than for the preparatory planning condition. No effects were found on general snack intake frequency or fruit intake. Future planning interventions should more explicitly compare changes in situational and general intake, as well as simultaneously assessed decreases in unhealthy intake and increases in healthy intake. PMID- 27671976 TI - Burnout syndrome in critical care team members: A monocentric cross sectional survey. AB - INTRODUCTION: There has been a growing interest in evaluating the occurrence of burnout syndrome (BOS) among intensive care units (ICU) team over recent years. The aims of this study were to determine the prevalence of BOS among staff working in the Amiens University Hospital and to assess associated factors. PATIENTS AND METHODS: Prospective observational study based on self-administered questionnaires filled in by physicians and non-physicians working in 3 ICUs. Demographic data, well-being assessment, work relationships, level of BOS and depressive symptoms were investigated. Logistic regression analysis was performed to identify variables independently associated with BOS. RESULTS: One hundred and sixty-one questionnaires were analysed. Participation rate was 90%. Thirty-two respondents were physicians and 129 were non-physicians. The prevalence of BOS was 51% and was not significantly different between physicians and non-physicians (56% versus 50%; P=0.501). Respondents who reported BOS less frequently had regular leisure activities (54 [66%] versus 70 [87%], P=0.001). In the BOS group, well-being was significantly lower (4.8+/-2.5/10 versus 6+/-2/10, P=0.001), a desire to leave the job was more frequently expressed (50 [61%] versus 32 [40%], P=0.009) and depressive symptoms were significantly more frequent (41 [50%] versus 21 [27%], P=0.002). Factors independently associated with BOS were regular leisure activities (OR 0.24 [0.1-0.59]; P=0.002), the presence of depressive symptoms (OR 2.71 [1.26-5.84]; P=0.011) and a well-being visual analogue scale>=5 (OR 0.40 [0.18-0.89]; P=0.024). CONCLUSIONS: BOS affects all ICU workers and is determined by multiple factors. Leisure activities and measures designed to improve well-being should be promoted. PMID- 27671977 TI - What are the factors associated with successful I-gelTM insertion and uneventful anaesthesia in children under age two? AB - BACKGROUND: Our purpose was to evaluate I-gelTM sizes 1 and 1.5. METHODS: I-gelTM insertion was attempted in 60 children<2 years of age undergoing short elective surgery. The main endpoints were the determination of independent factors associated with successful first attempt insertion and those associated with uneventful anaesthesia (i.e. no adverse events during insertion or during the intraoperative period of removal). RESULTS: Size 1 and size 1.5 I-gelTM devices were used (intraoperatively) in 33 and 27 cases, respectively. Median age and weight were 3 (1-12) months and 4.97 (4.00-9.00) kg. Ventilation modes were spontaneous breathing (8.3%), pressure support (45%), controlled pressure (15%) or volume (31.7%) ventilation. I-gelTM insertion was successful on the first attempt in 45 cases (75%). A time between induction and insertion>11min (OR: 4.85 [1.08-21.77]) and age<6 months (OR: 5.501 [1.20-16.8]) were identified as the independent factors of successful first attempt insertion (AUC: 0.715). Adverse events were reported in 35 (58.3%) cases, during insertion in 18 (30%) cases, during the intraoperative period in 25 (41.7%) cases and/or during recovery in 3 (5.08%) cases. Age<6 months (OR: 4.497 [1.197-16.89]) and I-gelTM removal in the operating room (OR: 6.034 [1.153-31.577]) were identified as independent factors associated with uneventful anaesthesia (AUC: 0.761). CONCLUSION: I-gelTM sizes 1 and 1.5 were interesting alternatives to intubation with all ventilation modes. However, the high incidence of adverse events calls for careful monitoring. The superiority of removal under anaesthesia must be confirmed. PMID- 27671978 TI - Pulmonary embolism of cement after knee prosthesis replacement. PMID- 27671979 TI - Postoperative complications following neonatal and infant surgery: Common events and predictive factors. AB - BACKGROUND: Data on major non-surgical postoperative complications following neonatal and infant surgery is lacking. The goal of the present study was to describe common major complications and their predictive factors. MATERIAL AND METHODS: The study consisted of a retrospective review of medical charts of patients less than 6months of age operated in our institution over one calendar year, excluding herniorraphy surgery. The data collected included demographics, preoperative ICU bed status, ASA status, a history of cardiac malformation, hyaline membrane disease (HMD) or necrotizing enterocolitis (NEC), preoperative haemoglobin, emergent surgery status, surgery type and duration, duration of anaesthesia and the need for intraoperative fluid boluses. Complications were analysed until the 30th postoperative day. Analyses included descriptive statistics and the determination of factors associated with non-surgical complications using univariate and multivariate statistics. RESULTS: The study included 168 patients. Their postnatal age was 48+/-48days. Overall, 37 patients experienced major postoperative non-surgical complications. The most common major complications were haemodynamic compromise (n=19, 11.3%), multiple organ dysfunction syndrome (MODS, n=8, 4.8%) and respiratory failure requiring ventilation (n=3, 1.8%). Surgical complications occurred in 8 cases (4.8%). Four factors were identified as being predictive of non-surgical complications: PCA<40 weeks, a history of cardiac malformation, HMD or NEC, preoperative ICU status and intraoperative fluid bolus administration. CONCLUSION: This study describes common non-surgical postoperative complications in neonates and infants, and their risk factors. They were much more common than surgical complications. Further studies should focus on preventive strategies addressing these complications. PMID- 27671980 TI - Spinal bupivacaine and clonidine for orthopaedic and general paediatric surgery in remote location. PMID- 27671981 TI - Health beliefs affect the correct replacement of daily disposable contact lenses: Predicting compliance with the Health Belief Model and the Theory of Planned Behaviour. AB - PURPOSE: To assess the compliance of Daily Disposable Contact Lenses (DDCLs) wearers with replacing lenses at a manufacturer-recommended replacement frequency. To evaluate the ability of two different Health Behavioural Theories (HBT), The Health Belief Model (HBM) and The Theory of Planned Behaviour (TPB), in predicting compliance. METHOD: A multi-centre survey was conducted using a questionnaire completed anonymously by contact lens wearers during the purchase of DDCLs. RESULTS: Three hundred and fifty-four questionnaires were returned. The survey comprised 58.5% females and 41.5% males (mean age 34+/-12years). Twenty three percent of respondents were non-compliant with manufacturer-recommended replacement frequency (re-using DDCLs at least once). The main reason for re using DDCLs was "to save money" (35%). Predictions of compliance behaviour (past behaviour or future intentions) on the basis of the two HBT was investigated through logistic regression analysis: both TPB factors (subjective norms and perceived behavioural control) were significant (p<0.01); HBM was less predictive with only the severity (past behaviour and future intentions) and perceived benefit (only for past behaviour) as significant factors (p<0.05). CONCLUSIONS: Non-compliance with DDCLs replacement is widespread, affecting 1 out of 4 Italian wearers. Results from the TPB model show that the involvement of persons socially close to the wearers (subjective norms) and the improvement of the procedure of behavioural control of daily replacement (behavioural control) are of paramount importance in improving compliance. With reference to the HBM, it is important to warn DDCLs wearers of the severity of a contact-lens-related eye infection, and to underline the possibility of its prevention. PMID- 27671982 TI - Measurement of saliva flow rate in healthy young humans: influence of collection time and mouthrinse water temperature. AB - The aim of the current study was to determine if unstimulated saliva flow (measured in MUl min-1 ) is affected by different durations of sample collection and by temperatures of mouthrinse water used before sample collection. In randomized order, participants provided 10 samples of unstimulated saliva at time points ranging from 1 to 6 min after rinsing with different temperatures of water (10, 20, and 30 degrees C). Data were analysed by one-way anova with post-hoc tests. Test-retest reliability was assessed using Bland-Altman plots and correlation coefficients. A larger volume of saliva was obtained over a longer collection time. No significant difference in saliva flow rate was observed between collection times [mean: 364 (95% CI: 332-397) MUl min-1 ]. Although rinsing with different temperatures of mouthrinse water resulted in no significant difference in saliva flow rates as a result of the mouthrinse water temperatures, 60% of the participants had a higher saliva flow rate after rinsing with mouthrinse water at a temperature of 10 degrees C compared with mouthrinse water at 20 and 30 degrees C, suggesting large individual variation (range: 24 420 MUl min-1 ). These findings provide justification for using saliva collection times of 1-6 min during sampling of unstimulated saliva. The large individual variations in saliva flow rate in response to different mouthrinse water temperatures suggest that standardization, control, and reporting of mouthrinse water temperature is warranted. PMID- 27671984 TI - Acute coronary syndrome-like presentation with prolonged QT interval: an unusual case of pheochromocytoma. AB - Pheochromocytoma is a rare adrenal gland tumour, usually alerting the physician by causing hypertensive tachycardic attacks. Patients with pheochromocytoma can rarely present with clinical signs similar to acute coronary syndrome. QT interval prolongation and ST segment changes due to pheochromocytoma have also been reported in the literature in a few case reports. We report a patient who had been admitted to the emergency department with chest pain, ischaemic ECG changes and marked QT prolongation. Despite a normal coronary angiogram, we observed that the QT interval and ST segment morphologies had changed during the hospitalisation period. Adrenal adenoma was diagnosed incidentally on abdominal CT scan, and the final diagnosis was pheochromocytoma. The tumour was successfully excised and the patient is now symptom free. When there is lack of a typical clinical picture, the diagnosis of pheochromocytoma might be challenging. It is also very crucial, since misdiagnosis can be life-threatening. PMID- 27671983 TI - Effects of occupational exposure to carbon black on peripheral white blood cell counts and lymphocyte subsets. AB - The International Agency for Research on Cancer has classified carbon black (CB) as a possible (Group 2B) human carcinogen. Given that most CB manufacturing processes result in the emission of various types of chemicals, it is uncertain if the adverse health effects that have been observed in CB-exposed workers are related to CB specifically or are due to other exposures. To address this issue, we conducted a cross-sectional molecular epidemiology study in China of 106 male factory workers who were occupationally exposed to pure CB and 112 unexposed male workers frequency-matched by age and smoking status from the same geographic region. Repeated personal exposure measurements were taken in workers before biological sample collection. Peripheral blood from all workers was used for the complete blood cell count and lymphocyte subsets analysis. Compared to unexposed workers, eosinophil counts in workers exposed to CB were increased by 30.8% (P = 0.07) after adjusting for potential confounders. When stratified by smoking status, statistically significant differences in eosinophils between CB exposed and unexposed workers were only present among never smokers (P = 0.040). Smoking is associated with alterations in various cell counts; however, no significant interaction between CB exposure and smoking status for any cell counts was observed. Given that inflammation, characterized in part by elevated eosinophils in peripheral blood, may be associated with increased cancer risk, our findings provide new biologic insights into the potential relationship between CB exposure and lung carcinogenesis. Environ. Mol. Mutagen. 57:589-604, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27671986 TI - De novo Propionibacterium acnes septic arthritis. AB - We report the third identifiable case of septic arthritis due to Propionibacterium acnes arising in the absence of prior surgical intervention. This anaerobic Gram-positive bacillus is now recognised as an important cause of postoperative infections, typically presenting in an indolent fashion some months after surgery. Reports of de novo septic arthritis due to P. acnes are exceedingly rare. Our case adds to the literature and significantly broadens the reported pathogenic potential of the organism, which in this instance has caused rapid and serious joint destruction. PMID- 27671987 TI - Lymphomatoid granulomatosis associated with azathioprine use for immune-mediated neuropathy. AB - Lymphomatoid granulomatosis (LG) is a rare Epstein-Barr virus-driven lymphoproliferative disorder that generally arises in immunosuppressed patients and which can be life-threatening. Here we describe the development of pulmonary LG in a patient on long-term azathioprine for immune-mediated neuropathy. Although azathioprine carries a boxed warning for malignancy, its association specifically with LG, an otherwise rare entity, is poorly recognised. Early recognition of drug-induced LG is critical, since discontinuation of the offending agent, and implementation of effective therapy can provide rapid clinical benefit in some patients. In this case, rituximab was used as an effective treatment for LG, which also provided an additional benefit of controlling the patient's underlying neuropathy. Further research is needed to identify vulnerable patients who are at high risk of developing drug-induced LG. PMID- 27671985 TI - Rapunzel syndrome: a rare cause of hypoproteinaemia and review of literature. AB - Rapunzel syndrome is an extremely rare condition associated with trichophagia (hair eating disorder) secondary to a psychiatric illness called trichotillomania (hair-pulling behaviour). It is most commonly seen in children and adolescents. Untreated cases can lead to a number of complications. We present a case of a middle-aged woman with sudden intractable vomiting and constipation associated with bilateral pedal oedema and significant weight loss. Laboratory investigations revealed low serum protein levels. Laparotomy was performed, and a hairball was removed from her stomach and ileum. The patient was managed with the help of a psychiatrist and was given nutritional support. We performed a comprehensive search and summarised data for a total of 88 cases. No time or language limit was placed. The purpose of this discussion is to highlight the clinical spectrum of Rapunzel syndrome and also to report its rare association with hypoproteinaemia. PMID- 27671988 TI - Congenital pulmonary airway malformation (CPAM) with initial presentation in an adult: a rare presentation of a rare disease. AB - Congenital pulmonary airway malformation (CPAM) is a rare congenital abnormality with unknown exact aetiology or clear genetic association. It is characterised by a failure of bronchial development and localised glandular overgrowth. Typically, it is diagnosed on prenatal ultrasound, only infrequently in children, and even less commonly in adults. We present a case of a 25-year-old man, with no previous lung diseases who presented with right-sided chest pain, fever and cough suggestive of pulmonary infection. Chest imaging, including CT scan, showed a large focal cystic mass within the right lower lobe along with ground glass opacities suggestive of CPAM. He was started on intravenous antibiotics. Bronchoscopy showed a large amount of pus in the right lung and bronchoalveolar lavage confirmed the microbiological diagnosis of methicillin-resistant Staphylococcus aureus. He improved with antibiotic treatment. He was discharged with 6-week course of antibiotics and follow-up afterward. PMID- 27671989 TI - The Impact of Disease and Drugs on Hip Fracture Risk. AB - We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged >=50 years (n = 117,494) including all incident hip fractures during 1 year (n = 477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0-S72.2) during 1 year (2009-2010). Exposures included: prevalence of (1) inpatient diseases [International Classification of Diseases (ICD) codes A00-T98 in the National Patient Register 1987-2010] and (2) prescribed drugs dispensed in 2010 or the year prior to fracture. We present age- and sex-standardized risk ratios (RRs), risk differences (RDs) and population attributable risks (PARs) of disease and drug categories in relation to hip fracture risk. All disease categories were associated with increased risk of hip fracture. Largest risk ratios and differences were for mental and behavioral disorders, diseases of the blood and previous fracture (RRs between 2.44 and 3.00; RDs (per 1000 person-years) between 5.0 and 6.9). For specific drugs, strongest associations were seen for antiparkinson (RR 2.32 [95 % CI 1.48-1.65]; RD 5.2 [1.1-9.4]) and antidepressive drugs (RR 1.90 [1.55-2.32]; RD 3.1 [2.0-4.3]). Being prescribed >=10 drugs during 1 year incurred an increased risk of hip fracture, whereas prescription of cardiovascular drugs or <=5 drugs did not appear to increase risk. Diseases inferring the greatest PARs included: cardiovascular diseases PAR 22 % (95 % CI 14-29) and previous injuries (PAR 21 % [95 % CI 16-25]; for specific drugs, antidepressants posed the greatest risk (PAR 16 % [95 % CI 12.0-19.3]). PMID- 27671990 TI - Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd-DTPA and USPIO-enhanced imaging. AB - High grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co-option in regions of invasive growth (in which the blood-brain barrier remains intact) and neoangiogenesis is a major challenge faced in the assessment of brain tumours by conventional MRI. A multiparametric MRI approach, incorporating native measurements and both Gd-DTPA (Magnevist) and ultrasmall superparamagnetic iron oxide (P904)-enhanced imaging, was used in combination with histogram and unsupervised cluster analysis using a k-means algorithm to examine the spatial distribution of vascular parameters, water diffusion characteristics and invasion in intracranially propagated rat RG2 gliomas and human MDA-MB-231 LM2-4 breast adenocarcinomas in mice. Both tumour models presented with higher DeltaR1 (the change in transverse relaxation rate R1 induced by Gd-DTPA), fractional blood volume (fBV) and apparent diffusion coefficient than uninvolved regions of the brain. MDA-MB-231 LM2-4 tumours were less densely cellular than RG2 tumours and exhibited substantial local invasion, associated with oedema, whereas invasion in RG2 tumours was minimal. These additional features were reflected in the more heterogeneous appearance of MDA-MB 231 LM2-4 tumours on T2 -weighted images and maps of functional MRI parameters. Unsupervised cluster analysis separated subregions with distinct functional properties; areas with a low fBV and relatively impermeable blood vessels (low DeltaR1 ) were predominantly located at the tumour margins, regions of MDA-MB-231 LM2-4 tumours with relatively high levels of water diffusion and low vascular permeability and/or fBV corresponded to histologically identified regions of invasion and oedema, and areas of mismatch between vascular permeability and blood volume were identified. We demonstrate that dual contrast MRI and evaluation of tissue diffusion properties, coupled with cluster analysis, allows for the assessment of heterogeneity within invasive brain tumours and the designation of functionally diverse subregions that may provide more informative predictive biomarkers. PMID- 27671991 TI - Prognostic models in male breast cancer. AB - PURPOSE: Breast cancer in men is uncommon; it accounts for 1 % of all patients with primary breast cancer. Its treatment is mostly extrapolated from its female counterpart. Accurate predictions are essential for adjuvant systemic treatment decision-making and informing patients. Several predictive models are available for female breast cancer (FBC) including the Morphometric Prognostic Index (MPI), Nottingham Prognostic Index (NPI), Adjuvant! Online and Predict. The aim of this study was to examine and compare the prognostic performance of these models for male breast cancer (MBC). METHODS: The population of this study consists of 166 MBC patients. The prognostic scores of the patients are categorized by good, (moderate) and poor, defined by the test itself (MPI and NPI) or based on tertiles (Adjuvant! Online and Predict). Survival according to prognostic score was compared by Kaplan-Meier analysis and differences were tested by logRank. The prognostic performances were evaluated with C-statistics. Calibration was done with the aim to estimate to what extent the survival rates predicted by Predict were similar to the observed survival rates. RESULTS: All prediction models were capable of discriminating between good, moderate and poor survivors. P-values were highly significant. Comparison between the models using C-statistics (n = 88) showed equal performance of MPI (0.67), NPI (0.68), Adjuvant! Online (0.69) and Predict (0.69). Calibration of Predict showed overestimation for MBC patients. CONCLUSION: In conclusion, MPI, NPI, Adjuvant! and Predict prognostic models, originally developed and validated for FBC patients, also perform quite well for MBC patients. PMID- 27671992 TI - Seasonal variability of respiratory syncytial virus infection in the Top End of the Northern Territory (2012-2014). AB - AIM: To determine the prevalence of respiratory syncytial virus (RSV) in the Top End of the Northern Territory and investigate potential drivers of seasonality including rainfall and humidex (humidity and heat index). METHODS: We performed a retrospective audit of laboratory confirmed cases of RSV from January 2012 to August 2014. Demographic details including age, sex and ethnicity were examined. RSV cases were correlated with monthly rainfall and humidex. RESULTS: There were 272 positive isolates detected from 4305 clinical samples (positivity rate 6.3%). The majority of cases occurred in children <12 months (n = 151, 55.5%), with a higher burden of disease seen in Indigenous compared to non-Indigenous infants in this age category (P < 0.005). The prevalence of RSV in the 0-5 years age category was 58/10 000 children per annum. Indigenous patients had higher prevalence rates (88.8/10 000 population per annum) and younger onset of infection (7.5 months; Interquartile range (IQR) 3-19 months compared to 13 months for non-Indigenous children; IQR 5 months to 2.4 years). RSV cases correlated most strongly with rainfall in the preceding month (r = 0.72). CONCLUSIONS: The Top End of the Northern Territory has a distinct RSV season that correlates with rainfall and humidex, which differs from Southern Australian disease patterns. PMID- 27671993 TI - Steak and Stupor: seizures and E. coli O157 infection. AB - Neurological complications of haemolytic uraemic syndrome (HUS) include altered states of consciousness, seizures, ischaemic stroke and encephalopathy. Adult onset HUS is uncommon, and there is only a limited literature reporting neurological complications in this population. We report an adult with Shiga toxin-associated HUS complicated by focal-onset non-convulsive status epilepticus, who made a full neurological recovery. PMID- 27671995 TI - Every operation is a special event. PMID- 27671994 TI - Retrospective evaluation of ultrasound-indeterminate renal multilocular cystic masses by using neutrophil-lymphocyte ratio and computed tomography. AB - PURPOSE: To evaluate the clinical usefulness of neutrophil-lymphocyte ratio (NLR) in differentiating the ultrasound-indeterminate renal multilocular cystic masses (RMCM) in comparison with computed tomography (CT) and whether NLR has additional benefits to CT on sensitivity of detecting the malignant. MATERIALS AND METHODS: Overall, 93 patients who underwent normal ultrasound with a conclusion of indeterminate RMCM were examined by NLR and CT within 30 days before surgery or follow-up from March to September 2014 at PLA General Hospital and enrolled in this retrospective study. Logistic regression model was performed to find independent predictors for differentiating true nature of RMCM; differences in the validity parameters and diagnostic power of CT, NLR, and their combination were compared using McNemar tests and AUC model, respectively. RESULTS: The final diagnoses of the 93 patients consisted of 36 patients with benign complex cysts, 16 with multilocular cystic renal cell carcinoma, 9 with multilocular cystic nephroma, and 32 with clear cell renal cell carcinoma. Higher NLR were strongly associated with malignant masses. Multivariate logistic regression analysis revealed that NLR could be an independent predictor for differentiating true nature of these masses (OR = 3.617; 95% CI: 1.219-10.727; P = 0.020). For detecting the malignant masses, the sensitivity, specificity, and accuracy were 71.9%, 80.6%, and 75.3% for CT and 57.9%, 88.9%, and 69.9% for NLR under cutoff value of 2.31, respectively, whereas those of CT+NLR were 89.5%, 69.4%, and 81.7%. No significant difference was found between CT and NLR in sensitivity (P = 0.185), specificity (P = 0.549), and accuracy (P = 0.428). But the sensitivity of CT+NLR was significantly higher than those of CT (P = 0.002) and NLR (P<0.001), respectively; AUC model analysis indicated that CT+NLR got the largest area of 0.795 (P<0.001, 95% CI: 0.693-0.896) in comparison with those of CT (area = 0.795, P<0.001, 95% CI: 0.661-0.864) and NLR (area = 0.734, P<0.001, 95% CI: 0.631-0.836). CONCLUSIONS: Given that NLR, under cutoff value of 2.31, had no diagnostic difference with CT in evaluating the ultrasound-indeterminate RMCM. However, combination of CT and NLR could increase the sensitivity of detecting malignant masses and acquire the best diagnostic power. Prospectively larger cohort and multicenter studies are still necessary. PMID- 27671996 TI - Resistance-training exercises with different stability requirements: time course of task specificity. AB - PURPOSE: The aim of the study was to assess the task-specificity (greater improvements in trained compared to non-trained tasks), transferability and time course adaptations of resistance-training programs with varying instability requirements. METHOD: Thirty-six resistance-trained men were randomized to train chest press 2 days week-1 for 10 week (6 repetitions * 4 series) using a Swiss ball, Smith machine or dumbbells. A six-repetition maximum-strength test with the aforementioned exercises and traditional barbell chest press were performed by all participants at the first, 7th, 14th and final training session in addition to electromyographic activities of the prime movers measured during isometric bench press. RESULTS: The groups training with the unstable Swiss-ball and dumbbells, but not the stable Smith-machine, demonstrated task-specificity, which became apparent in the early phase and remained throughout the study. The improvements in the trained exercise tended to increase more with instability (dumbbells vs. Smith machine, p = 0.061). The group training with Smith machine had similar improvements in the non-trained exercises. Greater improvements were observed in the early phase of the strength-training program (first-7th session) for all groups in all three exercises, but most notably for the unstable exercises. No differences were observed between the groups or testing times for EMG activity. CONCLUSION: These findings suggest that among resistance-trained individuals, the concept of task-specificity could be most relevant in resistance training with greater stability requirements, particularly due to rapid strength improvements for unstable resistance exercises. PMID- 27671997 TI - Not another type of potato: MC1R and the russet coloration of Burmese cats. AB - The Burmese is a breed of domestic cat that originated in Southeast Asia and was further developed in the United States. Variants in melanocortin 1 receptor (MC1R) causes common coat colour phenotypes in a variety of mammalian species but only limited colour variation in the domestic cat. Known as the extension (E) locus, melanocortin 1 receptor (MC1R) interacts with the agouti locus to produce the eumelanin and pheomelanin pigments. Recently, a novel reddish coloration, which is termed russet, was identified in the Burmese cat breed. Because this russet Burmese coloration changes with aging, MC1R was suggested as candidate gene. The similar colouration in specific lineages of Norwegian Forest cat known as amber (e) (c.250G>A; p.Asp84Asn) was excluded for this Burmese phenotype. The complete 954-bp coding region of MC1R was directly sequenced in russet Burmese and suspected carriers. A 3-bp deletion (c.439_441del) associated with the deletion of a phenyalanine (p.Phe146del) in the protein sequence was identified. All russet coloured cats were homozygous for the variant, and all obligate carriers were heterozygous, confirming that the deletion segregated concordantly with colouring in Burmese cats from the New Zealand foundation lineage. The variant was not identified in 442 cats from 26 different breeds and random-bred cats. Twenty-six Burmese from the USA did not have the variant. This MC1R variant defines a unique coloration and the second breed-specific MC1R variant in cats. The interactions of the two recessive feline MC1R alleles (E > e, er ) is unknown. PMID- 27671999 TI - [Von Hippel-Lindau disease : OCTA findings in retinal hemangioma]. AB - : The case report of a 35-year-old woman suffering from Hippel-Lindau syndrome (VHL) with retinal hemangiomas is presented. The patient developed macular edema with loss of vision and metamorphopsia. Laser treatment of hemangiomas improved the clinical picture. Hemangiomas were visualized using fluorescein angiography and optical coherence angiography. To our knowledge we describe retinal hemangiomas in VHL disease with the optical coherence tomographical angiography (OCTA) for the first time. CONCLUSION: OCTA is suitable as a new non-invasive method to visualize retinal hemangioma without intravenous contrast agent. PMID- 27671998 TI - [Platelet aggregation inhibitors and anticoagulants during ophthalmic interventions]. AB - In ophthalmology many patients undergo surgical treatment who need to take anticoagulant medication due to cardiovascular diseases. The proper handling of these drugs requires both correct assessment of the risk of thromboembolism as well as the rating of the risk of surgery-related hemorrhages. While there are established recommendations for estimation of the risk of thromboembolism based on a large body of prospective randomized trials, data regarding the evaluation of the related complications secondary to ophthalmic surgery are limited. In comparison to other surgical procedures, most interventions in ophthalmic surgery tend to have a relatively low risk of bleeding; therefore, in general there is no need to convert or discontinue anticoagulant drugs in patients undergoing opthalmic surgery. The sparse data available justifying the abrupt termination of anticoagulation are contrary to the approach currently widely distributed in clinical practice. This overview covers the relevant knowledge of the perioperative use of anticoagulant drugs. In addition, the data on the risk of hemorrhage in ophthalmological procedures are presented and discussed. PMID- 27672000 TI - A prospective, randomized, controlled trial of robot-assisted vs freehand pedicle screw fixation in spine surgery. AB - BACKGROUND: The purpose of this study was to compare the accuracy and safety of an instrumented posterior lumbar interbody fusion (PLIF) using a robot-assisted minimally invasive (Robot-PLIF) or a conventional open approach (Freehand-PLIF). METHODS: Patients undergoing an instrumented PLIF were randomly assigned to be treated using a Robot-PLIF (37 patients) and a Freehand-PLIF (41 patients). RESULTS: For intrapedicular accuracy, there was no significant difference between the groups (P = 0.534). For proximal facet joint accuracy, none of the 74 screws in the Robot-PLIF group violated the proximal facet joint, while 13 of 82 in the Freehand-PLIF group violated the proximal facet joint (P < 0.001). The average distance of the screws from the facets was 5.2 +/- 2.1 mm and 2.7 +/- 1.6 mm in the Robot-PLIF and Freehand-PLIF groups, respectively (P < 0.001). CONCLUSION: Robotic-assisted pedicle screw placement was associated with fewer proximal facet joint violations and better convergence orientations. PMID- 27672001 TI - Clarifying the PSA grey zone: The management of patients with a borderline PSA. AB - INTRODUCTION: Prostate specific antigen is a marker for prostate cancer and a key diagnostic tool, yet when to refer patients with a borderline PSA is currently unclear. This review describes how to assess a patient with borderline PSA and provides an algorithm for management. METHODS: Current literature on reference values, factors affecting PSA, indications for referral, non-invasive investigations and the role of MRI were reviewed. Medline and EMBASE were searched using MeSH terms. RESULTS: The literature suggests that a PSA of over 1.5 ng/mL should be used as a cut-off to consider further testing for all age groups. There is strong evidence to show that adjuncts are useful when interpreting PSA results, most notably percentage free PSA and proPSA. Considerable weighting should also be given to the ERSPC risk calculator when deciding when to refer. Multi-parametric MRI is valuable in closely examining suspicious lesions to reduce the number of negative biopsies. MRI fusion biopsy (TRUS, transrectal ultrasonography or transperineal) should be considered over standard TRUS biopsy to detect more clinically significant disease. CONCLUSIONS: Management of borderline PSA is not straightforward. A cut-off of 1.5 ng/mL should be used in conjunction with digital rectal exam, risk calculation and PSA adjuncts. Imaging and biopsy should utilise mpMRI to achieve improved diagnosis of clinically significant prostate cancer, with fewer unnecessary investigations. PMID- 27672002 TI - Segmented polynomials for incidence rate estimation from prevalence data. AB - The study considers the problem of estimating incidence of a non remissible infection (or disease) with possibly differential mortality using data from a(several) cross-sectional prevalence survey(s). Fitting segmented polynomial models is proposed to estimate the incidence as a function of age, using the maximum likelihood method. The approach allows automatic search for optimal position of knots, and model selection is performed using the Akaike information criterion. The method is applied to simulated data and to estimate HIV incidence among men in Zimbabwe using data from both the NIMH Project Accept (HPTN 043) and Zimbabwe Demographic Health Surveys (2005-2006). Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27672003 TI - Closing Uranyl Polyoxometalate Capsules with Bismuth and Lead Polyoxocations. AB - Uranyl polyoxometalate clusters are both fundamentally fascinating and potentially relevant to nuclear energy applications. With only ten years of development, there is still much to be discovered about heterometal derivatives and aqueous speciation and behavior. Herein, we show that it is possible to encapsulate the polyoxocations [Bi6 O8 ]2+ and [Pb8 O6 ]4+ in [(UO2 )(O2 )(OH)]2424- (denoted Bi@U24 and Pb@U24 ) in pure form and high yields despite the fact that under aqueous conditions, these compounds are stable on opposite ends of the pH scale. Moreover, [Pb8 O6 ]4+ is a formerly unknown PbII polynuclear species, both in solution and in the solid state. Raman spectroscopic and mass spectrometric analysis of the reaction solutions revealed the very rapid assembly of the nested clusters, driven by bismuth- or lead-promoted decomposition of excess peroxide, which inhibits U24 formation. Experimental and simulated small angle X-ray scattering data of Bi@U24 and Pb@U24 solutions revealed that this technique is very sensitive not only to the size and shape of the clusters, but also to the encapsulated species. PMID- 27672004 TI - Deferasirox pharmacokinetic and toxicity correlation in beta-thalassaemia major treatment. AB - OBJECTIVES: Deferasirox adverse effects include the following: gastrointestinal disturbance, mild elevations in serum creatinine levels and intermittent proteinuria; these events are dose-dependent and reversible with drug discontinuation, but this solution can lead to an inadequate iron chelation. For these reasons, interindividual variability of drug plasma concentration could help the clinical management of deferasirox dosage. We sought to describe deferasirox plasma exposure in a cohort of 60 adult patients. METHODS: A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from beta-thalassaemia adult patients. Samples obtained before and after 2, 4, 6 and 24 h drug administration were evaluated. Associations between variables were tested using the Pearson test. KEY FINDINGS: Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive correlation was found between deferasirox area under the concentration curve over 24 h and serum creatinine (r = 0.314; P = 0.018) and between area and drug dose (r = 0.311; P = 0.016). Moreover, a negative correlation resulted among area under the concentration curve over 24 h and serum ferritin (r = -0.291; P = 0.026) and among drug half-life and its dose (r = 0.319; P = 0.013). CONCLUSIONS: Treatment decision based on the individual characteristics could strongly contribute to minimize toxicity and increase efficacy of deferasirox therapy. PMID- 27672006 TI - p75 neurotrophin receptor regulates differential mineralization of rat ectomesenchymal stem cells. AB - OBJECTIVES: The aim of this study was to investigate whether p75NTR (p75 neurotrophin receptor) regulates differential mineralization capacity of rEMSCs (rat ectomesenchymal stem cells) and underlying mechanisms associated with Mage D1 (melanoma-associated antigens-D1). MATERIALS AND METHODS: Immunohistochemical staining of p75NTR in developing tooth germs was performed on E12.5d (embryonic 12.5 days) and E19.5d (embryonic 19.5 days). E12.5d EMSCs and E19.5d EMSCs were isolated in the same pregnant Sprague-Dawley rats from embryonic maxillofacial processes and tooth germs. p75NTR small-interfering RNA, p75NTR overexpression plasmid, Mage-D1 small-interfering RNA and recombined rat NGF were used to transfect cells. RESULTS: p75NTR was expressed in epithelial-mesenchymal interaction areas at E12.5d and E19.5d tooth germ development stages. E19.5d EMSCs had higher p75NTR expression levels and differential mineralization capacity but lower levels of cell proliferation. Under induction by mineralized culture medium, the potential of differential mineralization had identical trends in regulation of p75NTR in EMSCs; Mage-D1 did not fluctuate and TrkA was not expressed. Binding of p75NTR and Mage-D1 were detected. Mage-D1 knockdown significantly down-regulated expression of related genes, which NGF could not rescue. CONCLUSION: p75NTR participated in tooth germ development stages and mediated differential mineralization of EMSCs. p75NTR played a critical role in regulating the potential of differential mineralization of EMSCs. Mage-D1 seemed to act as a bridge in the underlying mechanism of effects of p75NTR. PMID- 27672007 TI - A comparative study of renal care in Brazil and Mexico: hemodialysis treatment from the perspective of ESRD sufferers. AB - Renal replacement therapy is the indicated treatment for individuals with chronic kidney disease (CKD) to survive. However, not all sick people have access to the same treatment. This study compares renal care in two developing countries with different health systems. Specifically, it explores hemodialysis treatment from the perspective of low-income individuals. A qualitative, comparative study was performed in Brazil and Mexico. Using purposive sampling, the research was based on open-ended interviews with nineteen participants with kidney failure undergoing hemodialysis treatment in public hospitals and ten relatives. According to our results, Brazilian participants perceived hemodialysis care as satisfactory because of health personnel courtesy as well as free access to dialysis treatment, prescription drugs, hospitalization and transportation. However, they reported deficiencies in the care they were receiving due to shortages of specialists, prescription drugs, laboratory tests and transportation. Mexican participants, in contrast, highlighted the catastrophic costs of medical care because they had no free access to renal therapy, nor adequate financial resources. Our findings suggest that low-income Brazilian CKD sufferers experience renal care differently, as they are more satisfied and face less obstacles with hemodialysis compared with those of Mexico. More studies on the topic are needed. PMID- 27672008 TI - Longing: A Patient and Caregiver Focused Clinical Diagnostic Validity (CDV) Study. AB - PURPOSE: To gather data from patients and caregivers about their personal experiences with longing. METHODS: Using Fehring's Clinical Diagnostic Validity model, patients and caregivers were surveyed for their experiences with longing. The survey was developed based on two previous research projects (a content analysis and survey of expert nurses). Approval for the study was received from the University of Wisconsin-Eau Claire Institutional Review Board. FINDINGS: None of the 84 attributes met major criteria (weighted ratios >= 0.8), but 19 met minor (weighted ratios of 0.60-0.79) across patients, caregivers, and combined scores. The proposed definition was supported by the respondents. CONCLUSIONS: The phenomenon of longing may exist. IMPLICATIONS FOR NURSING PRACTICE: There is evidence justifying the submission to NANDA-I for a new nursing diagnosis for longing. PMID- 27672005 TI - Comparison of Magnetic Microbubbles and Dual-modified Microbubbles Targeted to P selectin for Imaging of Acute Endothelial Inflammation in the Abdominal Aorta. AB - PURPOSE: Ultrasound molecular imaging (UMI) has potential to evaluate an inflammatory profile of endothelium. However, it is less successful in large arteries. This study compared magnetic microbubbles (MBs) selectively targeted to endothelial P-selectin and dual-targeting MBs in vitro and in vivo. PROCEDURES: MBs were modified with P-selectin antibody (MBPM) or isotype control antibody (MBCM) via a magnetic streptavidin bridge, and MBs were conjugated to P-selectin antibody (MBP) or both P-selectin antibody and PAA-sialyl Lewisx (MBD) via regular streptavidin linker. Adherence of MBs was determined by using a parallel plate flow chamber at variable shear stress (0.5-24 dyn/cm2). Adhesive and magnetic behaviors of MBs were analyzed at 4.0 dyn/cm2 or at a flow rate of 50 mm/s. Attachment of MBs to P-selectin was determined with contrast-enhanced ultrasound (CEU) imaging of murine abdominal aorta inflammation. The expression of P-selectin was assessed by immunohistochemistry. RESULTS: The adhesive efficacy of MBD was greater than MBP and MBCM, but lower than MBPM under all shear stress conditions (P < 0.05). The behaviors of fast-binding and rolling slow down were noted in MBD and MBPM; meanwhile, magnetic shifting of MBs centerline was presented in MBPM. Contrast video intensity (VI) from adhered MBPM to P-selectin of the inflammatory aorta was significantly higher than those from MBD and MBP (P < 0.05). CONCLUSIONS: MBPM may be a better molecular probe than MBD for detection of P-selectin on aorta with CEU, likely due to the shifting of axial distribution. Thus, it may improve the detection of the inflammatory profile on large arteries by UMI. PMID- 27672009 TI - High performance mass spectrometry based proteomics reveals enzyme and signaling pathway regulation in neutrophils during the early stage of surgical trauma. AB - PURPOSE: In clinical conditions trauma is associated with high mortality and morbidity. Neutrophils play a key role in the development of multiple organ failure after trauma EXPERIMENTAL DESIGN: To have a detailed understanding of the neutrophil activation at primary stages after trauma, neutrophils are isolated from control and surgical trauma rats in this study. Extracted proteins are analyzed using nano liquid chromatography coupled with tandem mass spectrometry. RESULTS: A total of 2924 rat neutrophil proteins are identified in our analysis, of which 393 are found differentially regulated between control and trauma groups. By using functional pathways analysis of the 190 proteins up-regulated in surgical trauma, we found proteins related to transcription initiation and protein biosynthesis. On the other hand, among the 203 proteins down-regulated in surgical trauma we found enrichment for proteins of the immune response, proteasome degradation and actin cytoskeleton. Overall, enzyme prediction analysis revealed that regulated enzymes are directly involved in neutrophil apoptosis, directional migration and chemotaxis. Our observations are then confirmed by in silico protein-protein interaction analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, our results reveal that neutrophils drastically regulate their biochemical pathways after the early stages of surgical trauma, showing lower activity. This implies higher susceptibility of the trauma patients to infection and bystander tissues damage. PMID- 27672010 TI - Biosynthesized Gold Nanoclusters and Iron Complexes as Scaffolds for Multimodal Cancer Bioimaging. AB - Cancer treatment has a far greater chance of success if the neoplasm is diagnosed before the onset of metastasis to vital organs. Hence, cancer early diagnosis is extremely important and remains a major challenge in modern therapeutics. In this contribution, facile and new method for rapid multimodal tumor bioimaging is reported by using biosynthesized iron complexes and gold nanoclusters via simple introduction of AuCl4- and Fe2+ ions. The observations demonstrate that the biosynthesized Au nanoclusters may act as fluorescent and computed tomography probes for cancer bioimaging while the iron complexes behave as effective contrast agent for magnetic resonance imaging. The biosynthesized iron complexes and gold nanoclusters are found biocompatible in vitro (MTT (3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay) and in vivo for all the vital organs of circulatory and excretory system. These observations raise the possibility that the biosynthesized probes may find applications in future clinical diagnosis for deep seated early neoplasms by multimodal imaging. PMID- 27672011 TI - The effect of adjunctive noncontact low frequency ultrasound on deep tissue pressure injury. AB - The optimal treatment for deep tissue pressure injuries has not been determined. Deep tissue pressure injuries represent a more ominous early stage pressure injury that may evolve into full thickness ulceration despite implementing the standard of care for pressure injury. A longitudinal prospective historical case control study design was used to determine the effectiveness of noncontact low frequency ultrasound plus standard of care (treatment group) in comparison to standard of care (control group) in reducing deep tissue pressure injury severity, total surface area, and final pressure injury stage. The Honaker Suspected Deep Tissue Injury Severity Scale (range 3-18[more severe]) was used to determine deep tissue pressure injury severity at enrollment (Time 1) and discharge (Time 2). A total of 60 subjects (Treatment = 30; Control= 30) were enrolled in the study. In comparison to the control group mean deep tissue pressure injury total surface area change at Time 2 (0.3 cm2 ), the treatment group had a greater decrease (8.8 cm2 ) that was significant (t = 2.41, p = 0.014, r2 = 0.10). In regards to the Honaker Suspected Deep Tissue Injury Severity Scale scores, the treatment group had a significantly lower score (7.6) in comparison to the control group (11.9) at time 2, with a mean difference of 4.6 (t = 6.146, p = 0.0001, r2 = 0.39). When considering the final pressure ulcer stage at Time 2, the control group were mostly composed of unstageable pressure ulcer (57%) and deep tissue pressure injury severity (27%). In contrast, the treatment group final pressure ulcer stages were less severe and were mostly composed of stage 2 pressure injury (50%) and deep tissue pressure injury severity (23%) were the most common at time 2. The results of this study have shown that deep tissue pressure injury severity treated with noncontact low frequency ultrasound within 5 days of onset and in conjunction with standard of care may improve outcomes as compared to standard of care only. PMID- 27672012 TI - Nonmodular Tapered Fluted Titanium Stems Osseointegrate Reliably at Short Term in Revision THAs. AB - BACKGROUND: The ideal femoral component for revision THA is undecided. Cylindrical nonmodular stems have been associated with stress shielding, whereas junctional fractures have been reported with tapered fluted modular titanium stems. We have used a tapered fluted nonmodular titanium femoral component (Wagner Self-locking [SL] femoral stem) to mitigate this risk. This component has been used extensively in Europe by its designer surgeons, but to our knowledge, it has not been studied in North America. Added to this, the design of the component has changed since early reports. QUESTIONS/PURPOSES: We asked: (1) Does the Wagner SL stem have low rates of rerevision and other complications at a minimum 2 years after surgery? (2) Is the Wagner SL stem associated with high levels of patient function and pain relief at a minimum 2 years after surgery? (3) Does the Wagner SL stem have low rates of subsidence at a minimum 2 years after surgery? (4) Is the Wagner SL stem associated with proximal femoral bone remodeling at a minimum 2 years after surgery? METHOD: Between May 2011 and December 2012, we performed 198 femoral revisions, of which 104 (53%) were performed using the Wagner SL femoral stem; during that period, our institution gradually shifted toward increasing use of these stems for all but the most severe revisions, in which modular fluted stems and proximal femoral replacements still are used on an occasional basis. Median followup in this retrospective study was 32 months (range, 24-46 months), and one patient was lost to followup before the 2-year minimum. The femoral deformities in this series were Paprosky Type I (10 hips), Paprosky Type II (26), Paprosky Type IIIA (52), Paprosky Type IIIB (nine), and Paprosky Type IV (two). Functional assessment was performed using the Oxford Hip Score (OHS), WOMAC, SF-12, and the University of California Los Angeles (UCLA) activity score. All complications and cases of revision were documented. All patients had radiographs performed within 1 year of the latest followup. These were assessed by two surgeons for signs of proximal femoral bone remodeling and subsidence. RESULTS: Complete preoperative scores were available for 98 patients (98 of 104; 94%). The mean OHS preoperatively and at final followup were 39 (SD, 15) and 87 (SD, 19), respectively (p < 0.001; mean difference, 48; 95% CI, 43-53). Average WOMAC scores were 44 (SD, 15) and 87 (SD, 20), respectively (p < 0.001; mean difference, 43; 95% CI, 38-48). At final followup, signs of restoration of proximal femoral bone stock was noted in 45 of 103 hips (44%). Six (six of 104; 6%) patients had subsidence of 10 mm to 15 mm. In the remainder (98 of 104; 94%), the mean subsidence was 2 mm (range, 0-9 mm). One revision was performed for loosening associated with infection. CONCLUSIONS: The Wagner SL stem is a viable option for patients with Paprosky Types II and III defects undergoing revision THA. This component provides high levels of patient function with low revision rates and low rates of subsidence during the early postoperative phase. They provide a viable alternative to modular components for treatment of Types II and III defects without the risk of junctional fractures. They can be used for very selected Type IV defects, however this extent of bone loss is most easily addressed with other techniques such as a proximal femoral replacement. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 27672014 TI - Efficacy of Foot and Ankle Corticosteroid Injections. AB - BACKGROUND: Corticosteroid injections have been used for a variety of foot and ankle pathologies over the years, and our aim was to evaluate the efficacy and safety of them in our clinic. MATERIALS AND METHODS: We performed a retrospective review of notes and a telephone questionnaire on the clinical outcome of all patients who underwent a corticosteroid injection of the foot or ankle in a year. All procedures were performed in an outpatient setting by a consultant musculoskeletal radiologist using either ultrasound or X-ray guidance and had a minimum of 2 years of follow-up. RESULTS: Overall, 314 of 365 (86%) patients reported a significant improvement in symptoms, and 242 (66%) reported complete resolution of their pain, with 107 (29%) remaining asymptomatic at the 2-year follow-up. The mode time of recurrence of pain was 3 months. Fifty-one (14%) underwent a further injection and 88 (24%) underwent operative intervention within the follow-up period. Complication rates in our series were low. There were no reported infections. Complications occurred in 5 patients (1.3%), including steroid flare, pain, and plantar plate ruptures. CONCLUSION: Corticosteroid injections were a safe and effective option for treating a variety of foot and ankle conditions and reduced the need for surgery. They were particularly effective for the treatment of ankle soft tissue impingement. They appear ineffective in providing significant improvement in pain for longer than 3 months in conditions such as plantar fasciitis and hallux rigidus. LEVEL OF EVIDENCE: IV, case series. PMID- 27672013 TI - What is the Diagnostic Accuracy of Aspirations Performed on Hips With Antibiotic Cement Spacers? AB - BACKGROUND: Periprosthetic joint infection is a serious complication after THA and commonly is treated with a two-stage revision. Antibiotic-eluting cement spacers are placed for local delivery of antibiotics. Aspirations may be performed before the second-stage reimplantation for identification of persistent infection. However, limited data exist regarding the diagnostic parameters of synovial fluid aspiration with or without saline lavage from a hip with an antibiotic-loaded cement spacer. QUESTIONS/PURPOSES: We asked: (1) For hips with antibiotic cement spacers, does saline lavage influence the diagnostic validity of aspirations? (2) What is the diagnostic accuracy of preoperative aspirations performed on hips with antibiotic cement spacers using the Musculoskeletal Infection Society (MSIS) criteria, stratified by saline and nonlavage? (3) For hips with antibiotic spacers, what are the optimal thresholds for synovial fluid white blood cell (WBC) count and polymorphonuclear neutrophil (PMN) percentage for diagnosing infections? METHODS: One hundred seventy-four hips (155 patients) with antibiotic-eluting cement spacers inserted between October 2012 and July 2015 were reviewed. Of these, 98 hips (80 patients) met the inclusion criteria and were included in the analysis (77 nonlavage, 21 saline lavage aspirations). Laboratory data from the aspiration and preoperative workup and intraoperative details were collected. Infection status of each hip procedure was determined based on a modified MSIS criteria using serologic, histologic, and intraoperative findings (sinus tract communicating with the joint at surgery or two positive intraoperative periprosthetic cultures with the same organism or two of the three following criteria: elevated erythrocyte sedimentation rate [ESR] [> 30 mm/hour] and C-reactive protein [CRP] [> 10 mg/L], a single positive intraoperative periprosthetic tissue culture, or a positive histologic analysis of periprosthetic tissue [> 5 neutrophils per high power field]). The diagnostic parameters were calculated for the MSIS criteria thresholds for synovial fluid (ie, WBC count > 3000 cells/uL and PMN percentage > 80%). Optimal thresholds were calculated for the corrected synovial WBC count and PMN percentage with a receiver operating characteristic curve. Separate analyses were performed for the hips with successful aspirations (nonlavage group) and those with saline lavage aspirations. RESULTS: The WBC count and PMN percentage were higher in hips with infection than in hips without infection when nonlavage aspirations were done (WBC count, 6680 cells/uL +/- 6980 cells/uL vs 2001 +/- 4825; mean difference, 4679; 95% CI, 923-8436; p = 0.015; PMN percentage, 83% +/- 13% vs 44% +/- 30%; mean difference, 39%; 95% CI, 39%-49%; p < 0.001) and the findings between infected and noninfected aspirations were not different when saline lavage aspirations were done (WBC count, 782 cells/uL +/- 696 vs 307 cells/uL +/- 343; mean difference, 475; 95% CI, -253 to 1203; p = 0.161; PMN percentage, 67% +/- 15% vs 58% +/- 28%; mean difference, 10%; 95% CI, -11% to 30%; p = 0.331). Aspirations performed without lavage yielded good diagnostic accuracy in all parameters (WBC count, 78% [95% CI, 70%-86%]; PMN percentage. 79% [95% CI, 70% 88%]; positive culture: 84% [95% CI, 81%-90%]; at least one of the above: 79% [95% CI, 70%-88%]); but in the saline lavage group, none had WBC counts above the threshold (diagnostic accuracies for WBC count, 0%; PMN percentage, 71% [95% CI, 62%-86%]; positive culture, 76% [95% CI, 76%-86%]; at least one: 71% [95% CI, 57% 91%]). Because saline lavage did not result in differences between aspirations from infected and noninfected hips, we calculated the optimal thresholds in the nonlavage group only; the optimal threshold for synovial WBC count was 1166 cells/uL and for synovial PMN the percentage was 68%, which corresponds to WBC count diagnostic accuracy of 78% (95% CI, 69%-87%) and PMN percentage accuracy of 78% (95% CI, 69%-87%). CONCLUSIONS: Because the MSIS criteria thresholds resulted in suboptimal sensitivities owing to a higher number of false negatives, we recommend considering lower WBC count and PMN percentage thresholds for hip spacer aspirations. Furthermore, the WBC count and PMN percentage results from aspirations performed with saline lavage are not reliable for treatment decisions. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 27672015 TI - Realtime Achilles Ultrasound Thompson (RAUT) Test for the Evaluation and Diagnosis of Acute Achilles Tendon Ruptures. AB - BACKGROUND: Acute complete Achilles tendon ruptures are commonly missed injuries. We propose the Realtime Achilles Ultrasound Thompson (RAUT) test, a Thompson test under ultrasound visualization, to aid in the diagnosis of these injuries. We hypothesized that RAUT testing would provide improved diagnostic characteristics compared with static ultrasound. METHODS: Twenty-two consecutive patients with operatively confirmed acute Achilles tendon ruptures were prospectively evaluated with RAUT testing and static ultrasonography. RAUT video recordings and static ultrasound images from both ruptured and uninjured sides were randomized and graded by a group of novice reviewers and a group of expert attendings. From these observations, sensitivity, specificity, positive predictive value, and negative predictive value for RAUT and static ultrasound were calculated. In addition, kappa interobserver coefficients were computed. Forty-seven novice reviewers and 11 foot and ankle attendings made a total of 4136 and 528 observations, respectively. RESULTS: For static ultrasound, sensitivity and specificity were 76.8% and 74.8% for the novice reviewers and 79.6% and 86.4% for the attendings, respectively. For RAUT testing, sensitivity and specificity were 87.2% and 81.1% for the novice group and 86.4% and 91.7% for the attending group, respectively. The kappa coefficient was 0.62 and 0.27 for novice and attending RAUT reviewers, indicating substantial and fair agreement, respectively, but only 0.46 and 0.12 for static ultrasonography, representing moderate and slight agreement, respectively. CONCLUSION: RAUT testing was a sensitive and specific test, providing a cost-effective adjunct to the clinical examination when diagnosing acute Achilles tendon ruptures. This test can be used by surgeons with minimal training in ultrasonography. LEVEL OF EVIDENCE: Level II, diagnostic study. PMID- 27672016 TI - Biomechanical Comparison of 3 Current Ankle Syndesmosis Repair Techniques. AB - BACKGROUND: Significant debate exists regarding optimal repair for unstable syndesmosis injuries. Techniques range from screw fixation, suture-button fixation, or a combination of the two. In this study, 3 common repairs were compared using a simulated weightbearing protocol with internal and external rotation of the foot. METHODS: Twenty-four lower leg specimens with mean age 54 years (range, 38-68 years) were used for testing. Following creation of a complete syndesmotic injury (AITFL, ITFL, PITFL, interosseous membrane), specimens were repaired using 1 of 3 randomly assigned techniques: (1) one 3.5-mm syndesmotic screw, (2) 1 suture-button construct, and (3) 2 divergent suture button constructs. Repairs were cycled for 500 cycles between 7.5 Nm of internal/external rotation torque under a constant 750 N axial compressive load in a neutral dorsiflexion position. At 0, 10, 100, and 500 cycles, torsional cyclic loading was interrupted to assess torsional resistance to rotation within a physiologic range of motion (15 degrees external rotation to 10 degrees internal rotation). Torque (Nm), rotational position (degrees), and 3-dimensional data were collected throughout the testing to characterize relative spatial relationships of the tibiofibular articulation. RESULTS: There were no significant differences between repair techniques in resistance to internal and external rotation with respect to the intact syndesmosis. Three-dimensional analysis revealed significant differences between repair techniques for sagittal fibular translation with external rotation of the foot. Screw fixation had the smallest magnitude of posterior sagittal translation (2.5 mm), and a single suture-button construct demonstrated the largest magnitude of posterior sagittal translation (4.6 mm). Screw fixation also allowed for significantly less anterior sagittal translation with internal rotation of the foot (0.1 mm) when compared to both 1 (2.7 mm) and 2 (2.9 mm) suture-button constructs. CONCLUSION: All repairs provided comparable rotational stability to the syndesmosis; however, no repair technique completely restored rotational stability and tibiofibular anatomic relationships of the preinjury state. CLINICAL RELEVANCE: Constructs were comparable across most conditions; however, when repairing injuries with a suture button construct, a single suture-button construct may not provide sufficient resistance to sagittal translation of the fibula. PMID- 27672017 TI - Effectiveness of Headless Bioabsorbable Screws for Fixation of the Scarf Osteotomy. AB - BACKGROUND: Scarf osteotomy has been used in hallux valgus surgery due to its large fixation surface for screws and low postoperative complications. However, screws may cause skin irritation from their head, which may require an additional surgical procedure to remove. METHODS: This study included 115 patients (106 females and 9 males, 115 feet) who underwent hallux valgus correction with a scarf osteotomy using bioabsorbable screws between September 2010 and September 2012. Preoperative and postoperative 1-month and 1-year radiographic measurements, including intermetatarsal angle (IMA), hallux valgus angle (HVA), distal metatarsal articular angle (DMAA), proximal phalangeal articular angle (PPAA), and lateral translational distance (LTD), were obtained. American Orthopaedic Foot & Ankle Society (AOFAS) hallux/forefoot scores were used for patient satisfaction. RESULTS: Preoperative mean values of HVA, IMA, and PPA of 32.8 degrees, 14.6 degrees, and 7.52 degrees, respectively, improved to 10.7 degrees, 6.0 degrees, and 4.6 degrees, respectively at 1-year follow up (P < .05). The difference in LTD between the 1-month and 1-year follow-up was not statistically significant. AOFAS hallux/forefoot score improved from 69.1 to 96.1 at the 1-year follow up (P < .001). Complete screw absorption was not seen radiographically. Sixteen feet had complications reported. One patient complained of skin irritation over a small protrusion of the screw, and another patient had a foreign body reaction. There were 3 patients with neurologic injury from a popliteal block and 3 patients with dorsal cutaneous nerve symptoms. Four feet had metatarsal fracture during surgery. CONCLUSION: We found the scarf osteotomy using bioabsorbable screws to have satisfactory clinical and radiographic results with a low complication rate. LEVEL OF EVIDENCE: Level IV, case series. PMID- 27672018 TI - Microcirculation measured by vascular occlusion test during desflurane remifentanil anesthesia is superior to that in propofol-remifentanil anesthesia in patients undergoing thoracic surgery: subgroup analysis of a prospective randomized study. AB - General anesthesia can affect microcirculatory properties. However, differential effects on the microcirculation according to the anesthetic technique used during thoracoscopic surgery have not been well documented. We conducted a randomized clinical trial in which the effects of desflurane and propofol, both with remifentanil, on systemic arterial oxygenation during one-lung ventilation were compared in patients undergoing thoracoscopic surgery. As a subgroup analysis, we compared the effects of two commonly used anesthetic techniques, desflurane remifentanil (n = 52) and propofol-remifentanil (n = 48), on tissue oxygen saturation using a vascular occlusion test in patients undergoing thoracoscopic surgery. Tissue oxygen saturation was higher in the desflurane than the propofol group (mean +/- standard deviation, 83 +/- 6 vs. 80 +/- 9, 84 +/- 6 vs. 76 +/- 10, and 87 +/- 7 vs. 77 +/- 10 % at 30 and 60 min of one-lung ventilation and at two-lung ventilation; adjusted p = 0.026, <0.001, and <0.001, respectively). The recovery slope during the vascular occlusion test, reflecting microvascular reperfusion adequacy, was higher in the desflurane than the propofol group during surgery (mean difference, 0.5 %/s; 95 % CI 0.0-0.9 %/s; p = 0.037). Desflurane remifentanil anesthesia is associated with better microcirculation than propofol remifentanil anesthesia in patients undergoing thoracoscopic surgery. PMID- 27672019 TI - Developing the Evidence Base in Pediatric Oncology Nursing Practice for Promoting Health-Related Quality of Life in Pediatric Oncology Patients. AB - Research has shown that self-esteem and hopefulness are positively related among female childhood cancer survivors (CCS) and contribute to their health-related quality of life (HRQOL). HRQOL remains a significant outcome of treatment for CCS. This study examined the relationships among self-esteem, hopefulness, and HRQOL in young adult female CCS to inform the development of evidence-based practice guidelines for pediatric oncology nursing practice. An online survey was conducted with a sample of young adult female CCS from 58 treatment centers across the United States at 4 time points: at baseline and at 6 weeks, 3 months, and 6 months after initial measurement time. The relationships between self esteem, hopefulness, and HRQOL were statistically significant (Time 1, P = .05; Times 2, 3, and 4, P = .01) across all measurement times. These findings identify hopefulness and self-esteem as determinants of HRQOL and suggest that caring practices among pediatric oncology nurses that support psychosocial adjustment through promoting self-esteem and hopefulness have the potential to support HRQOL among young adult female CCS. These outcomes support the development of evidence based practice guidelines to influence HRQOL outcomes among these survivors. PMID- 27672020 TI - The changing view of eukaryogenesis - fossils, cells, lineages and how they all come together. AB - Eukaryogenesis - the emergence of eukaryotic cells - represents a pivotal evolutionary event. With a fundamentally more complex cellular plan compared to prokaryotes, eukaryotes are major contributors to most aspects of life on Earth. For decades, we have understood that eukaryotic origins lie within both the Archaea domain and alpha-Proteobacteria. However, it is much less clear when, and from which precise ancestors, eukaryotes originated, or the order of emergence of distinctive eukaryotic cellular features. Many competing models for eukaryogenesis have been proposed, but until recently, the absence of discriminatory data meant that a consensus was elusive. Recent advances in paleogeology, phylogenetics, cell biology and microbial diversity, particularly the discovery of the 'Candidatus Lokiarcheaota' phylum, are now providing new insights into these aspects of eukaryogenesis. The new data have allowed the time frame during which eukaryogenesis occurred to be finessed, a more precise identification of the contributing lineages and the biological features of the contributors to be clarified. Considerable advances have now been used to pinpoint the prokaryotic origins of key eukaryotic cellular processes, such as intracellular compartmentalisation, with major implications for models of eukaryogenesis. PMID- 27672021 TI - Autophagy in adhesion and migration. AB - Autophagy, a pathway for lysosomal-mediated cellular degradation, has recently been described as a regulator of cell migration. Although the molecular mechanisms underlying autophagy-dependent motility are only beginning to emerge, new work demonstrates that selective autophagy mediated by the autophagy cargo receptor, NBR1, specifically promotes the dynamic turnover of integrin-based focal adhesion sites during motility. Here, we discuss the detailed mechanisms through which NBR1-dependent selective autophagy supports focal adhesion remodeling, and we describe the interconnections between this pathway and other established regulators of focal adhesion turnover, such as microtubules. We also highlight studies that examine the contribution of autophagy to selective degradation of proteins that mediate cellular tension and to integrin trafficking; these findings hint at further roles for autophagy in supporting adhesion and migration. Given the recently appreciated importance of selective autophagy in diverse cellular processes, we propose that further investigation into autophagy-mediated focal adhesion turnover will not only shed light onto how focal adhesions are regulated but will also unveil new mechanisms regulating selective autophagy. PMID- 27672022 TI - HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2. AB - Although the mechanism underlying modulation of transcription factors in myogenesis has been well elucidated, the function of the transcription cofactors involved in this process remains poorly understood. Here, we identified HMGB2 as an essential nuclear transcriptional co-regulator in myogenesis. HMGB2 was highly expressed in undifferentiated myoblasts and regenerating muscle. Knockdown of HMGB2 inhibited myoblast proliferation and stimulated its differentiation. HMGB2 depletion downregulated Myf5 and cyclin A2 at the protein but not mRNA level. In contrast, overexpression of HMGB2 promoted Myf5 and cyclin A2 protein upregulation. Furthermore, we found that the RNA-binding protein IGF2BP2 is a downstream target of HMGB2, as previously shown for HMGA2. IGF2BP2 binds to mRNAs of Myf5 or cyclin A2, resulting in translation enhancement or mRNA stabilization, respectively. Notably, overexpression of IGF2BP2 could partially rescue protein levels of Myf5 and cyclin A2, in response to HMGB2 decrease. Moreover, depletion of HMGB2 in vivo severely attenuated muscle repair; this was due to a decrease in satellite cells. Taken together, these results highlight the previously undiscovered and crucial role of the HMGB2-IGF2BP2 axis in myogenesis and muscle regeneration. PMID- 27672023 TI - Moderate Alcohol Consumption Is Associated With Left Ventricular Diastolic Dysfunction in Nonalcoholic Hypertensive Patients. AB - Ethanol consumption is associated with left ventricular dysfunction in heavy ethanol drinkers. The effect of moderate ethanol intake on left ventricular function in hypertension, however, is unknown. We investigated the relationship between ethanol consumption and cardiac changes in nonalcoholic hypertensive patients. In 335 patients with primary hypertension, we assessed daily ethanol consumption by questionnaires that combined evaluation of recent and lifetime ethanol exposure and examined cardiac structure and function by echocardiography. Patients with abnormal liver tests, previous cardiovascular events, left ventricular ejection fraction <50%, and creatinine clearance <30 mL/min 1.72 m2 were excluded. Left ventricular hypertrophy was found in 21% of hypertensive patients and diastolic dysfunction was detected in 50% by tissue-Doppler imaging. Ethanol consumption was comparable in hypertensive patients with and without left ventricular hypertrophy, whereas patients with left ventricular diastolic dysfunction had significantly greater consumption than patients with normal ventricular filling. Left atrial diameter, e' wave velocity, e'/a' ratio, and E/e' ratio changed progressively with increasing levels of ethanol consumption, and prevalence of left ventricular diastolic dysfunction increased with a change that became statistically significant in patients consuming 20 g/d of ethanol or more. The e' wave velocity was inversely correlated with ethanol consumption, and multivariate logistic regression indicated that ethanol consumption predicted diastolic dysfunction independently of age, body mass index, blood pressure, insulin sensitivity, and left ventricular mass index. In conclusion, ethanol consumption is independently associated with left ventricular diastolic dysfunction in nonalcoholic hypertensive patients and might contribute to development of diastolic heart failure. PMID- 27672024 TI - Klotho and Pulmonary Hypertension: Spinning a Yarn or the Thread of Life? PMID- 27672025 TI - Monocrotaline-Induced Pulmonary Hypertension Involves Downregulation of Antiaging Protein Klotho and eNOS Activity. AB - The objective of this study is to investigate whether stem cell delivery of secreted Klotho (SKL), an aging-suppressor protein, attenuates monocrotaline induced pulmonary vascular dysfunction and remodeling. Overexpression of SKL in mesenchymal stem cells (MSCs) was achieved by transfecting MSCs with lentiviral vectors expressing SKL-green fluorescent protein (GFP). Four groups of rats were treated with monocrotaline, whereas an additional group was given saline (control). Three days later, 4 monocrotaline-treated groups received intravenous delivery of nontransfected MSCs, MSC-GFP, MSC-SKL-GFP, and PBS, respectively. Ex vivo vascular relaxing responses to acetylcholine were diminished in small pulmonary arteries (PAs) in monocrotaline-treated rats, indicating pulmonary vascular endothelial dysfunction. Interestingly, delivery of MSCs overexpressing SKL (MSC-SKL-GFP) abolished monocrotaline-induced pulmonary vascular endothelial dysfunction and PA remodeling. Monocrotaline significantly increased right ventricular systolic blood pressure, which was attenuated significantly by MSC SKL-GFP, indicating improved PA hypertension. MSC-SKL-GFP also attenuated right ventricular hypertrophy. Nontransfected MSCs slightly, but not significantly, improved PA hypertension and pulmonary vascular endothelial dysfunction. MSC-SKL GFP attenuated monocrotaline-induced inflammation, as evidenced by decreased macrophage infiltration around PAs. MSC-SKL-GFP increased SKL levels, which rescued the downregulation of SIRT1 (Sirtuin 1) expression and endothelial NO synthase (eNOS) phosphorylation in the lungs of monocrotaline-treated rats. In cultured endothelial cells, SKL abolished monocrotaline-induced downregulation of eNOS activity and NO levels and enhanced cell viability. Therefore, stem cell delivery of SKL is an effective therapeutic strategy for pulmonary vascular endothelial dysfunction and PA remodeling. SKL attenuates monocrotaline-induced PA remodeling and PA smooth muscle cell proliferation, likely by reducing inflammation and restoring SIRT1 levels and eNOS activity. PMID- 27672026 TI - Central Angiotensin-II Increases Blood Pressure and Sympathetic Outflow via Rho Kinase Activation in Conscious Rabbits. AB - Elevated sympathetic tone and activation of the renin-angiotensin system are pathophysiologic hallmarks of hypertension, and the interactions between these systems are particularly deleterious. The importance of Rho kinase as a mediator of the effects of angiotensin-II (AngII) in the periphery is clear, but the role of Rho kinase in sympathoexcitation caused by central AngII is not well established. We hypothesized that AngII mediates its effects in the brain by the activation of the RhoA/Rho kinase pathway. Chronically instrumented, conscious rabbits received the following intracerebroventricular infusion treatments for 2 weeks via osmotic minipump: AngII, Rho kinase inhibitor Fasudil, AngII plus Fasudil, or a vehicle control. AngII increased mean arterial pressure over the course of the infusion, and this effect was prevented by the coadministration of Fasudil. AngII increased cardiac and vascular sympathetic outflow as quantified by the heart rate response to metoprolol and the depressor effect of hexamethonium; coadministration of Fasudil abolished both of these effects. AngII increased baseline renal sympathetic nerve activity in conscious animals and impaired baroreflex control of sympathetic nerve activity; again Fasudil coinfusion prevented these effects. Each of these end points showed a statistically significant interaction between AngII and Fasudil. Quantitative immunofluorescence of brain slices confirmed that Rho kinase activity was increased by AngII and decreased by Fasudil. Taken together, these data indicate that hypertension, elevated sympathetic outflow, and baroreflex dysfunction caused by central AngII are mediated by Rho kinase activation and suggest that Rho kinase inhibition may be an important therapeutic target in sympathoexcitatory cardiovascular diseases. PMID- 27672028 TI - Parsimonious Correction of Heart Rate Variability for Its Dependency on Heart Rate. PMID- 27672027 TI - Association Between Early Life Growth and Blood Pressure Trajectories in Black South African Children. AB - Early growth is associated with blood pressure measured on one occasion, but whether early life growth patterns are associated with longitudinal blood pressure trajectories is under-researched. Therefore, we sought to examine the association between early growth and blood pressure trajectories from childhood to adulthood. Blood pressure was measured on 7 occasions between ages 5 and 18 years in the Birth to Twenty cohort study, and conditional variables for growth in infancy and mid-childhood were computed from anthropometric measures (n=1937, 52% girls). We used a group-based trajectory modeling approach to identify distinct height-adjusted blood pressure trajectories and then tested their association with growth between birth and mid-childhood adjusting for several covariates. Three trajectory groups were identified for systolic and diastolic blood pressure: lower, middle, and upper in boys and girls, separately. In boys, predictors of the middle or upper systolic blood pressure trajectories versus the lower trajectory were in birth weight (odds ratio 0.75 [95% confidence interval 0.58-0.96] per SD) and relative weight gain in infancy (4.11 [1.25-13.51] per SD). In girls, greater relative weight gain and linear growth in both infancy and mid-childhood were consistently associated with an almost 2-fold higher likelihood of being in the upper versus lower systolic blood pressure trajectory. The associations for the diastolic blood pressure trajectories were inconsistent. These findings emphasize the importance of identifying children at risk of progression to high blood pressure. Accelerated growth in infancy and mid childhood may be a key target for early life intervention in prevention of elevated blood pressure progression. PMID- 27672029 TI - The Role of the Autonomic Nervous System in the Regulation of Aortic Stiffness. AB - The autonomic nervous system is important in regulating blood pressure, but whether it regulates aortic stiffness is more contentious. We conducted 3 studies in young, healthy individuals to address this important question. Study 1 was a cross-sectional study of 347 subjects with detailed measurements of hemodynamics and heart rate variability. In study 2, 9 subjects were given a bolus of intravenous nicotinic ganglion blocker, pentolinium, or saline in a random order and hemodynamics and heart rate variability were assessed before and after. In study 3, changes in hemodynamics and heart rate variability were assessed during stimulation of the sympathetic nervous system with the use of isometric handgrip exercise in 12 subjects. Study 1: aortic pulse wave velocity (P=0.003) was lowest in the subjects with the highest parasympathetic activity, but after adjusting for mean arterial pressure, the effect was abolished (P=0.3). Study 2: after pentolinium, sympathetic and parasympathetic activity fell (P=0.001 for both), mean arterial pressure, and heart rate increased (P=0.004 and P=0.04, respectively), but there was no change in pulse wave velocity in comparison to placebo (P=0.1). Study 3: during handgrip exercise, sympathetic activity (P=0.003), mean arterial pressure (P<0.0001), and aortic pulse wave velocity increased (P=0.013). However, pulse wave velocity adjusted for mean arterial pressure did not change (P=0.1). The main finding of these studies is that in young healthy subjects, the autonomic nervous system does not have a pressure independent role in the regulation of aortic stiffness. However, these findings may not apply to patients with increased sympathetic tone or hypertension. PMID- 27672031 TI - Updates on Endothelial Functions of Proangiogenic Prokineticin. PMID- 27672030 TI - Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats. AB - Despite the striking differences between male and female physiology, female physiology is understudied. In response, the National Institutes of Health is promulgating new policies to increase the use of female organisms in preclinical research. Females are commonly believed to have greater variability than males because of the estrous cycle, but recent studies call this belief into question. Effects of estrous cycling on mean arterial pressure were assessed in female Dahl S rats using telemetry and vaginal cytometry and found that estrous cycling did not affect mean arterial pressure magnitude or variance. Data from the PhysGen arm of the Program for Genomic Applications was used to compare male and female variance and coefficient of variation in 142 heart, lung, vascular, kidney, and blood phenotypes, each measured in hundreds to thousands of individual rats from over 50 inbred strains. Seventy-four of 142 phenotypes from this data set demonstrated a sex difference in variance; however, 59% of these phenotypes exhibited greater variance in male rats rather than female. Remarkably, a retrospective power analysis demonstrated that only 16 of 74 differentially variable phenotypes would be detected when using an experimental cohort large enough to detect a difference in magnitude. No overall difference in coefficient of variation between male and female rats was detected when analyzing these 142 phenotypes. We conclude that variability of 142 traits in male and female rats is similar, suggesting that differential treatment of males and females for the purposes of experimental design is unnecessary until proven otherwise, rather than the other way around. PMID- 27672032 TI - Transcranial direct current stimulation for patients with benign essential blepharospasm: a case report. PMID- 27672033 TI - Assessment of free and cued recall in Alzheimer's disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test. AB - Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients' groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients' groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD. PMID- 27672034 TI - Crosstalk between androgen and pro-inflammatory signaling remodels androgen receptor and NF-kappaB cistrome to reprogram the prostate cancer cell transcriptome. AB - Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-kappaB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells. Co-stimulation of LNCaP cells with androgen and pro-inflammatory cytokine TNFalpha invoked a transcriptome which was very distinct from that induced by either stimulation alone. The altered transcriptome that included gene programs linked to cell migration and invasiveness was orchestrated by significant remodeling of NF kappaB and AR cistrome and enhancer landscape. Although androgen multiplied the NF-kappaB cistrome and TNFalpha restrained the AR cistrome, there was no general reciprocal tethering of the AR to the NF-kappaB on chromatin. Instead, redistribution of FOXA1, PIAS1 and PIAS2 contributed to the exposure of latent NF kappaB chromatin-binding sites and masking of AR chromatin-binding sites. Taken together, concomitant androgen and pro-inflammatory signaling significantly remodels especially the NF-kappaB cistrome, reprogramming the PC cell transcriptome in fashion that may contribute to the progression of PC. PMID- 27672035 TI - Global tRNA misacylation induced by anaerobiosis and antibiotic exposure broadly increases stress resistance in Escherichia coli. AB - High translational fidelity is commonly considered a requirement for optimal cellular health and protein function. However, recent findings have shown that inducible mistranslation specifically with methionine engendered at the tRNA charging level occurs in mammalian cells, yeast and archaea, yet it was unknown whether bacteria were capable of mounting a similar response. Here, we demonstrate that Escherichia coli misacylates non-methionyl-tRNAs with methionine in response to anaerobiosis and antibiotic exposure via the methionyl-tRNA synthetase (MetRS). Two MetRS succinyl-lysine modifications independently confer high tRNA charging fidelity to the otherwise promiscuous, unmodified enzyme. Strains incapable of tRNA mismethionylation are less adept at growth in the presence of antibiotics and stressors. The presence of tRNA mismethionylation and its potential role in mistranslation within the bacterial domain establishes this response as a pervasive biological mechanism and connects it to diverse cellular functions and modes of fitness. PMID- 27672037 TI - SAC3B, a central component of the mRNA export complex TREX-2, is required for prevention of epigenetic gene silencing in Arabidopsis. AB - Epigenetic regulation is important for organismal development and response to the environment. Alteration in epigenetic status has been known mostly from the perspective of enzymatic actions of DNA methylation and/or histone modifications. In a genetic screen for cellular factors involved in preventing epigenetic silencing, we isolated an Arabidopsis mutant defective in SAC3B, a component of the conserved TREX-2 complex that couples mRNA transcription with nuleo cytoplasmic export. Arabidopsis SAC3B dysfunction causes gene silencing at transgenic and endogenous loci, accompanied by elevation in the repressive histone mark H3K9me2 and by reduction in RNA polymerase Pol II occupancy. SAC3B dysfunction does not alter promoter DNA methylation level of the transgene d35S::LUC, although the DNA demethylase ROS1 is also required for d35S::LUC anti silencing. THP1 and NUA were identified as SAC3B-associated proteins whose mutations also caused d35S::LUC silencing. RNA-DNA hybrid exists at the repressed loci but is unrelated to gene suppression by the sac3b mutation. Genome-wide analyses demonstrated minor but clear involvement of SAC3B in regulating siRNAs and DNA methylation, particularly at a group of TAS and TAS-like loci. Together our results revealed not only a critical role of mRNA-export factors in transcriptional anti-silencing but also the contribution of SAC3B in shaping plant epigenetic landscapes. PMID- 27672038 TI - Nucleolytic processing of aberrant replication intermediates by an Exo1-Dna2-Sae2 axis counteracts fork collapse-driven chromosome instability. AB - Problems during DNA replication underlie genomic instability and drive malignant transformation. The DNA damage checkpoint stabilizes stalled replication forks thus counteracting aberrant fork transitions, DNA breaks and chromosomal rearrangements. We analyzed fork processing in checkpoint deficient cells by coupling psoralen crosslinking with replication intermediate two-dimensional gel analysis. This revealed a novel role for Exo1 nuclease in resecting reversed replication fork structures and counteracting the accumulation of aberrant intermediates resembling fork cleavage products. Genetic analyses demonstrated a functional interplay of Exo1 with Mus81, Dna2 and Sae2 nucleases in promoting cell survival following replication stress, suggestive of concerted nucleolytic processing of stalled forks. While Mus81 and other Structure Specific Endonucleases do not contribute to obvious collapsed fork transitions, Dna2 promotes reversed fork resection likely by facilitating Exo1 access to nascent strands. Instead, Sae2 cooperates with Exo1 in counteracting putative fork cleavage events linked to double strand breaks formation and increased gross chromosomal rearrangement rates. Our data indicate that in checkpoint deficient cells diverse nuclease activities interface to eliminate aberrant replication intermediates and prevent chromosome instability. PMID- 27672040 TI - A fast and powerful W-test for pairwise epistasis testing. PMID- 27672041 TI - UK needs "radical rethink" on public health, say medical scientists. PMID- 27672039 TI - Concerted effects of heterogeneous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells. AB - Traditionally recognized as an RNA splicing regulator, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) can also bind to double-stranded DNA and function in trans as a vitamin D response element (VDRE)-binding protein. As such, hnRNPC1/C2 may couple transcription induced by the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) with subsequent RNA splicing. In MG63 osteoblastic cells, increased expression of the 1,25(OH)2D target gene CYP24A1 involved immunoprecipitation of hnRNPC1/C2 with CYP24A1 chromatin and RNA. Knockdown of hnRNPC1/C2 suppressed expression of CYP24A1, but also increased expression of an exon 10-skipped CYP24A1 splice variant; in a minigene model the latter was attenuated by a functional VDRE in the CYP24A1 promoter. In genome wide analyses, knockdown of hnRNPC1/C2 resulted in 3500 differentially expressed genes and 2232 differentially spliced genes, with significant commonality between groups. 1,25(OH)2D induced 324 differentially expressed genes, with 187 also observed following hnRNPC1/C2 knockdown, and a further 168 unique to hnRNPC1/C2 knockdown. However, 1,25(OH)2D induced only 10 differentially spliced genes, with no overlap with differentially expressed genes. These data indicate that hnRNPC1/C2 binds to both DNA and RNA and influences both gene expression and RNA splicing, but these actions do not appear to be linked through 1,25(OH)2D mediated induction of transcription. PMID- 27672043 TI - Seasonal changes of cholinergic response in the atrium of Arctic navaga cod (Eleginus navaga). AB - Fishes of north-temperate latitudes exhibit marked seasonal changes in electrical excitability of the heart partly as an outcome of temperature-dependent changes in the density of major K+ ion currents: delayed rectifiers (IKr, IKs) and background inward rectifier (IK1). In the arctic teleost, navaga cod (Eleginus navaga), IKr and IK1 are strongly up-regulated in winter. The current study tests the hypothesis that the ligand-gated K+ current, the acetylcholine-activated inward rectifier, IKACh, is also modified by seasonal acclimatization in atrial myocytes of navaga. In sinoatrial preparations of the summer-acclimatized (SA) navaga, 10-6 M carbamylcholine chloride (CCh) caused slowing of heart rate, shortening of atrial action potential (AP) duration and a drastic reduction of AP amplitude, eventually resulting in inexcitability. In winter-acclimatized (WA) atria CCh slowed HR and reduced AP duration, but reduction of AP amplitude was modest and never resulted in inexcitability. The difference in cholinergic response between SA and WA navaga is explained by seasonal changes in IKACh density. The peak density of IKACh, induced by 10-5 M CCh, at the common experimental temperature (+6 degrees C) was 0.97 +/- 0.28 pA/pF in SA navaga but only 0.183 +/- 0.013 pA/pF in WA navaga (a 5.3-fold difference, P < 0.05). At acclimatization temperatures of the fish IKACh density was 2.8 +/- 0.50 (at +12 degrees C) and 0.11 +/- 0.06 pA/pF (at +3 degrees C) (a 26-fold difference, P < 0.05) for SA and WA navaga, respectively. Thus, acclimatization to summer induces a drastic up-regulation of the atrial IKACh, which effectively shortens atrial AP. The reverse temperature compensation of the atrial IKACh may be advantageous in summer under variable water temperatures and oxygen concentrations by reducing workload of the heart. PMID- 27672042 TI - Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer. AB - PURPOSE: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC. METHODS: In this retrospective study, tissue samples from 472 Japanese patients with CRC, stratified for MSI, were analyzed to determine the prognostic value of BRAF V600E, as assessed using IHC. Mutations in 254 patients were evaluated using the direct sequencing method to check for concordance. RESULTS: The frequency of MSI-H was 9.3 % (44/472), and BRAF V600E mutation was detected immunohistochemically in 8.7 % patients (41/472). The sensitivity and specificity for detection of BRAF V600E mutations by IHC were 100 % (17/17) and 98.7 % (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical tumor site (P = 0.0035), histological type (P < 0.0001), and MSI status (P < 0.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio = 1.500, P = 0.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard ratio = 2.621, P = 0.0004). CONCLUSIONS: IHC using a BRAF V600E-specific antibody was useful for diagnosis and concurred with direct sequencing results. CRC cases could be stratified by combining BRAF V600E mutation and MSI status as a prognostic factor in Japanese patients. PMID- 27672045 TI - Total mercury in fresh and processed tuna marketed in Galicia (NW Spain) in relation to dietary exposure. AB - Mercury is a toxic trace metal, which can accumulate to levels threatening human and environmental health. In this study, contents of total mercury have been determined by ICP-MS spectrometry in fresh and processed tuna (110 samples) purchased from supermarkets in NW Spain. Mercury was present in all samples analyzed; however, only one sample of fresh tuna (1.070 mg kg-1 wet weight (w.w.)) slightly exceeded the limit of the EU (1.0 mg kg-1 w.w.). The average mercury concentration in processed tuna was lower than fresh, 0.306 mg kg-1 w.w., and ranged from 0.080 to 0.715 mg kg-1 w.w. Results were compared with literature data. In regard to the three types of preparation-packaging media for canned tuna, total Hg content was found in the following order: olive oil > natural > pickled sauce; the last showed significant statistical differences (p < 0.01) with the other two preparations. Between the two evaluated canned tuna species, significant statistical differences (p = 0.008) were observed and Thunnus alalunga presented a greater mean content (0.332 +/- 0.114 mg kg-1 w.w.) compared to Thunnus albacares (0.266 +/- 0.171 mg kg-1 w.w.).Taking into account the AESAN recommendation for adults and children, as well as the EU regulations and the tuna consumption by the Spanish population, the Hg levels obtained in this study pose no risk to consumer health. However, additional studies, a monitoring process, and efforts to reduce Hg concentration in tuna would be necessary, as well as considering other sources of exposure to Hg. PMID- 27672044 TI - Environmental pollutants: genetic damage and epigenetic changes in male germ cells. AB - About a quarter of the human diseases occurs for exposure to air pollution. The male reproductive system, and especially spermatogenesis, seems to be particularly sensitive. As result, male infertility is increasing in industrial countries becoming a top priority for public health. In addition to psychological distress and economic constraints, poorer semen quality may have trans generational effects including congenital malformations in the offspring and predispose to later onset adult diseases. Genetic and epigenetic alterations are involved in the failure of spermatogenesis. In this paper, we reviewed the major evidences of the effects of air pollutants on male infertility as well as the role of sperm DNA damage and epigenetic changes in affecting spermatogenesis. A better knowledge on the effects of air contaminants on the molecular mechanisms leading to infertility is of huge importance to help clinicians in identifying the cause of infertility but above all, in defining preventive and therapeutic protocols. PMID- 27672046 TI - Stability assessment of hydro dispersive nanometric permethrin and its biosafety study towards the beneficial bacterial isolate from paddy rhizome. AB - Nanopesticides such as nanopermethrin can serve as an alternative to conventional pesticides causing eco-toxicity. The nanoformulation of this pyrethroid pesticide was carried out by solvent evaporation of pesticide-loaded microemulsion. The Z average for the nanopermethrin dispersion in paddy field water was found to be 169.2 +/- 0.75 nm with a polydispersity index of 0.371 that exhibits uniform dispersion. Further, the nanopermethrin (NP) dispersion exhibited an effective stability in the paddy field water for a duration of 48 h with a Z average of 177.3 +/- 1.2 nm and a zeta potential of -30.7 +/- 0.9 mV. The LC50 of the nanopermethrin against Culex tritaeniorhynchus in the field condition was found to be 0.051 MUg/mL. In addition to the stability assessment, the biosafety of the nanopermethrin was commenced on the beneficial bacterial isolate Enterobacter ludwigii (VITSPR1) considered as plant growth-promoting rhizobacteria. The toxic effect of nanopesticide was compared to its bulk counterpart, i.e. bulk permethrin (BP) at a concentration of 100 ug/mL, and the nanopesticide was found to be potentially safe. The results of biomarker enzymatic assays (lipid peroxidase, glutathione reductase, lactate dehydrogenase) displayed insignificant (p < 0.05) toxicity of NP towards the bacterial cells compared to BP. The live dead cell staining and SEM analysis illustrated negligible toxicity of NP towards the bacteria. The non-toxic behaviour of the NP towards the non-target species was studied which displayed the eco-safe property of NP. PMID- 27672047 TI - Biochemical Characterization of Extracellular Cellulase from Tuber maculatum Mycelium Produced Under Submerged Fermentation. AB - Interaction of truffle mycelium with the host plant involves the excretion of extracellular enzymes. The ability of Tuber maculatum mycelium to produce an extracellular cellulase during submerged fermentation was demonstrated for the first time. T. maculatum mycelia were isolated and tested for extracellular cellulase production at variable pH on solid agar medium, and the highest activity was observed at pH 7.0. Furthermore, T. maculatum was subjected to submerged fermentation in basal salt medium for cellulase production. Under optimized conditions using sodium carboxymethyl cellulose (0.5 % w/v) as carbon source and an initial pH of 7.0, the enzyme production yielded 1.70 U/mL of cellulase in the cell-free supernatant after 7 days of incubation time. The optimum of the obtained cellulase's activity was at pH 5.0 and a temperature of 50 degrees C. The enzyme showed good thermostability at 50 degrees C by retaining 99 % of its maximal activity over an incubation time of 100 min. The cellulase activity was inhibited by Fe2+ and slightly activated by Mn2+ and Cu2+ at 1 mM concentration. The results indicated that truffle mycelium is utilizing cellulosic energy source in the root system, and the optimal conditions are those existing in the acidic Finnish soil. PMID- 27672049 TI - In vitro evolution of phi29 DNA polymerase using isothermal compartmentalized self replication technique. AB - Compartmentalized self replication (CSR) is widely used for in vitro evolution of thermostable DNA polymerases able to perform PCR in emulsion. We have modified and adapted CSR technique for isothermal DNA amplification using mezophilic phi29 DNA polymerase and whole genome amplification (WGA) reaction. In standard CSR emulsified bacterial cells are disrupted during denaturation step (94-96 degrees C) in the first circles of PCR. Released plasmid DNA that encodes target polymerase and the thermophilic enzyme complement the emulsified PCR reaction mixture and start polymerase gene amplification. To be able to select for mezophilic enzymes we have employed multiple freezing-thawing cycles of emulsion as a bacterial cell wall disruption step instead of high temperature incubation. Subsequently WGA like plasmid DNA amplification could be performed by phi29 DNA polymerase applying different selection pressure conditions (temperature, buffer composition, modified dNTP, time, etc.). In our case the library of random phi29 DNA polymerase mutants was subjected to seven selection rounds of isothermal CSR (iCSR). After the selection polymerase variant containing the most frequent mutations was constructed and characterized. The mutant phi29 DNA polymerase can perform WGA at elevated temperatures (40-42 degrees C), generate two to five times more of DNA amplification products, and has significantly increased half life at 30 and 40 degrees C, both in the presence or the absence of DNA substrate. PMID- 27672048 TI - Engineering a minimal G protein to facilitate crystallisation of G protein coupled receptors in their active conformation. AB - G protein-coupled receptors (GPCRs) modulate cytoplasmic signalling in response to extracellular stimuli, and are important therapeutic targets in a wide range of diseases. Structure determination of GPCRs in all activation states is important to elucidate the precise mechanism of signal transduction and to facilitate optimal drug design. However, due to their inherent instability, crystallisation of GPCRs in complex with cytoplasmic signalling proteins, such as heterotrimeric G proteins and beta-arrestins, has proved challenging. Here, we describe the design of a minimal G protein, mini-Gs, which is composed solely of the GTPase domain from the adenylate cyclase stimulating G protein Gs Mini-Gs is a small, soluble protein, which efficiently couples GPCRs in the absence of Gbetagamma subunits. We engineered mini-Gs, using rational design mutagenesis, to form a stable complex with detergent-solubilised beta1-adrenergic receptor (beta1AR). Mini G proteins induce similar pharmacological and structural changes in GPCRs as heterotrimeric G proteins, but eliminate many of the problems associated with crystallisation of these complexes, specifically their large size, conformational dynamics and instability in detergent. They are therefore novel tools, which will facilitate the biochemical and structural characterisation of GPCRs in their active conformation. PMID- 27672052 TI - Editorial: Graphene-based materials in nanomedicine. PMID- 27672050 TI - Evaluating the potential of a loop-extended scorpion toxin-like peptide as a protein scaffold. AB - Grafting of exogenous bioactive sites or functional motifs onto structurally stable scaffolds to gain new functions represents an important research direction in protein engineering. Some engineered proteins have been developed into therapeutic drugs. MeuNaTxalpha-3 (abbreviated as MT-3) is a newly characterized scorpion sodium channel toxin-like peptide isolated from the venom of the scorpion Mesobuthus eupeus, which contains a rigid scaffold highly similar to classical scorpion sodium channel toxins and an extension of eight amino acids in its J-loop region. This extended loop constitutes a flexible region extruded from the scaffold and could be substituted by exogenous functional sequences. In this study, we experimentally evaluated the scaffold potential of MT-3 through grafting two small antimicrobial motifs to replace residues within the loop. Functional assays showed that the two engineered molecules exhibited elevated antimicrobial potency, as compared with the unmodified scaffold, without structural disruption, providing experimental evidence in favor of MT-3 as a promising scaffold in protein engineering. PMID- 27672051 TI - Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression Is associated with vessel invasion and shortened survival. AB - Mucins play pivotal roles in influencing cancer biology, for example affecting carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to investigate the significance of expression profiles of two mucins in particular, MUC1 and MUC2, their correlations with various clinicopathological features, and prognosis in gallbladder adenocarcinoma (GBAC). We performed immunohistochemistry from patients with surgically resected GBAC, using antibodies against mucin core proteins MUC1/DF3 and MUC2/Ccp58 in 81 paraffin-embedded tumor samples. MUC1 or MUC2 expression was considered to be high when >= 20% or 10% of the GBAC cells showed positive staining, respectively. High MUC1 expression was revealed to have a significant relationship to the presence of pathologically lymphatic and vascular invasion, and regional lymph node metastasis. By contrast, high MUC2 expression showed a significant correlation with pathologically perineural invasion, T stage >= 3, and post-operative recurrence. Moreover, MUC1 showed significantly positive co-expression and potentially complementary correlations with MUC2. Multivariate analyses demonstrated that the high MUC1 expression group had significantly shorter disease-specific survival times. However, the combination of both high MUC1 and MUC2 expression did not predict worse outcome in GBACs. Therefore, although each mucin has a somewhat important role in the pathogenesis of GBAC progression, MUC1 can independently predict vessel invasion and poor prognosis in patients with GBAC. The detection of MUC1 might well offer a useful parameter for providing clinical management and treatment against postsurgical GBACs. PMID- 27672053 TI - The Association between Alcohol Consumption and Breast Density: A Systematic Review and Meta-analysis. AB - BACKGROUND: Percent breast density (PBD) is a strong risk factor for breast cancer that is influenced by several other risk factors for the disease. Alcohol consumption is associated with an increased risk of breast cancer with an uncertain association with PBD. We have carried out a systematic review and meta analysis to examine the association of alcohol consumption with PBD. METHODS: We searched nine databases to identify all relevant studies on the association between alcohol intake and breast density. Two independent investigators evaluated and selected 20 studies that were included in our analyses. We divided the studies into three groups according to the methods used to measure and analyze the association of breast density with alcohol consumption. RESULTS: Meta analysis of the 11 studies that used quantitative methods to measure and analyze PBD as a continuous variable found a statistically significant difference in PBD when comparing the highest with the lowest alcohol level [beta = 0.84; 95% confidence interval (CI), 0.12-1.56]. Three studies that used quantitative methods to measure PBD and categories of PBD for analysis had a summary OR = 1.81 (95% CI, 1.07-3.04). Five studies that used categories to classify PBD and analyze their association with alcohol intake had a summary OR = 1.78 (95% CI, 0.90-3.51). CONCLUSIONS: These results suggest that there is a positive association between alcohol intake and PBD. IMPACT: Alcohol may increase the risk of breast cancer associated with PBD. Cancer Epidemiol Biomarkers Prev; 26(2); 170-8. (c)2016 AACR. PMID- 27672055 TI - Is Pelvic Inflammatory Disease a Risk Factor for Ovarian Cancer? AB - BACKGROUND: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive, and only few cohort studies have been conducted. METHODS: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978-2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype. RESULTS: For ovarian cancer overall, we observed no association with PID (HR, 1.05; 95% CI, 0.92-1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR, 1.19; 1.00 1.41; P = 0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer. CONCLUSIONS: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes. IMPACT: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies. Cancer Epidemiol Biomarkers Prev; 26(1); 104-9. (c)2016 AACR. PMID- 27672056 TI - Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences. AB - BACKGROUND: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886-1977. METHODS: A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886-1928 and 1929-1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs. RESULTS: Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2-) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50-54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8-6.9 and 2.5; 95% CI, 1.2-5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3-0.5), Luminal B (HER2-; HR 0.5; 95% CI, 0.3-0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2-0.9). CONCLUSIONS: We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2-) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype. IMPACT: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625-34. (c)2016 AACR. PMID- 27672054 TI - Shifts in the Fecal Microbiota Associated with Adenomatous Polyps. AB - BACKGROUND: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. METHODS: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). RESULTS: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. CONCLUSIONS: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. IMPACT: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85-94. (c)2016 AACR. PMID- 27672057 TI - Once Again: Oribatid Mites and Skin Alkaloids in Poison Frogs. PMID- 27672058 TI - Response to Heethoff, Norton, and Raspotnig: Ant and Mite Diversity Drives Toxin Variation in the Little Devil Poison Frog and Erratum. AB - Our recent publication titled "Ant and Mite Diversity Drives Toxin Variation in the Little Devil Poison Frog" aimed to describe how variation in diet contributes to population differences in toxin profiles of poison frogs. Some poison frogs (Family Dendrobatidae) sequester alkaloid toxins from their arthropod diet, which is composed mainly of ants and mites. Our publication demonstrated that arthropods from the stomach contents of three different frog populations were diverse in both chemistry and species composition. To make progress towards understanding this trophic relationship, our main goal was to identify alkaloids that are found in either ants or mites. With the remaining samples that were not used for chemical analysis, we attempted to identify the arthropods using DNA barcoding of cytochrome oxidase 1 (CO1). The critique of Heethoff, Norton, and Raspotnig refers to the genetic analysis of a small number of mites. Here, we respond to the general argument of the critique as well as other minor issues detailed by Heethoff, Norton, and Raspotnig. PMID- 27672059 TI - Treatment satisfaction of home-based telehealth versus in-person delivery of prolonged exposure for combat-related PTSD in veterans. AB - Introduction Although there is growing support that evidence-based psychotherapies (EBPs) delivered in-person and through telehealth are equivalent in terms of symptom reduction for posttraumatic stress disorder (PTSD), there has been far less investigation comparing these treatment modalities in terms of patient satisfaction. The present study investigated participant satisfaction and perception of the quality of service delivery within a clinical trial comparing the delivery of an EBP, Prolonged Exposure (PE) for PTSD, through home-based telehealth and in-person services. Methods Veterans ( N = 67) with PTSD were randomized to receive PE via video telehealth technology ( n = 27) or via in person delivery ( n = 40). Participants completed service demographic questions, PTSD symptom assessments, and satisfaction and service delivery perception questionnaires. Results Analyses of covariance were used to investigate the influence of treatment modality on patient satisfaction and perceived quality of service delivery, while controlling for demographics and PTSD symptoms. No differences were observed on the majority of measures, with the exception of participants in the telehealth condition endorsing willingness to drive further for telehealth services as compared with participants in the in-person condition. Discussion Findings illustrate participant satisfaction and acceptance of EBPs delivered via telehealth at a level consistent with that of in-person services. Preliminary findings suggest that the experience of receiving telehealth services may be associated with increased willingness to participate in telehealth services again. Together, these findings of patient satisfaction and acceptance of telehealth services support the ongoing delivery of EBPs via telehealth as well as their future expansion. PMID- 27672060 TI - Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse. AB - The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through beta-adrenergic receptors (AR). Here, we wished to define the role played by the ARbeta3 isoform in this process. This study focused on the ARbeta3 knockout mice (ARbeta3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARbeta3KO mice defend core temperature during cold exposure (4 degrees C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARbeta3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARbeta3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARbeta3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARbeta3 inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation. PMID- 27672062 TI - Biomechanical Analysis of Stability of Posterior Antiglide Plating in Osteoporotic Pronation Abduction Ankle Fracture Model With Posterior Tibial Fragment. AB - BACKGROUND: We performed a biomechanical comparison of 2 methods for operative stabilization of pronation-abduction stage III ankle fractures; group 1: Anterior posterior lag screws fixing the posterior tibial fragment and lateral fibula plating (LSLFP) versus group 2: locked plate fixation of the posterior tibial fragment and posterior antiglide plate fixation of the fibula (LPFP). METHODS: Seven pairs of fresh-frozen osteoligamentous lower leg specimens (2 male, and 5 female donors) were used for the biomechanical testing. Bone mineral density (BMD) of each specimen was assessed by means of dual-energy x-ray absorptiometry. After open transection of the deltoid ligament, an osteotomy model of pronation abduction stage III ankle fracture was created. Specimens were systematically assigned to LSLFP (group 1, left ankles) or LPPFP (group 2, right ankles). After surgery, all specimens were evaluated via CT to verify reduction and fixation. Axial load was then applied onto each specimen using a servohydraulic testing machine starting from 0 N (Zwick/Roell, Ulm, Germany) at a speed of 10 N/s with the foot fixed in a 10 degrees pronation and 15 degrees dorsiflexion position. Construct stiffness, yield, and ultimate strength were measured and dislocation patterns were documented with a high-speed camera. The normal distribution of all data was analyzed using Shapiro-Wilk test. The group comparison was performed using paired Student t test. Statistical significance was assumed at a P value of .05. RESULTS: All specimens had BMD values consistent with osteoporosis. BMD values did not differ between the left and right ankles of the same pair ( P = .762). The mean BMD values between feet of men (0.603 g/cm2) and women (0.329 g/cm2) were statistically different ( P = .005). The ultimate strength for LSLFP (group 1) with 1139 +/- 669 N and LPPFP (group 2) with 2008 +/- 943 N was statistically different ( P = .036) as well as the yield in LSLFP (group 1) 812 +/- 452 N and LPPFD (group 2) 1292 +/- 625 N ( P = .016). Construct stiffness trended to be higher in group 2 (179 +/- 100 kNn) compared to group 1 (127 +/- 73 kN/m) but this difference was not statistically significant ( P = .120). BMD correlated with bone-construct failure. CONCLUSION: Fixation of the posterior tibial edge with a posterolateral locking plate resulted in higher biomechanical stability than anterior-posterior lag screw fixation in an osteoporotic pronation abduction fracture model. CLINICAL RELEVANCE: The clinical implication of this biomechanical study is that the posterior antiglide plating might be advantageous in patients with osteoporotic pronation abduction stage III ankle fracture. PMID- 27672063 TI - Correction of Hallux Valgus Interphalangeus With an Osteotomy of the Distal End of the Proximal Phalanx (Distal Akin Osteotomy). AB - BACKGROUND: Operative correction of a symptomatic hallux valgus interphalangeus (HVI) deformity is often achieved with an osteotomy at the proximal end of the proximal phalanx (Akin osteotomy). However, the apex of the typical HVI deformity (center of rotation angle) is at the interphalangeal joint of the hallux. This study was done to evaluate the results of performing a medial closing wedge osteotomy at the distal end of the proximal phalanx. METHODS: Thirty-three patients (33 feet) underwent an osteotomy at the distal end of the proximal phalanx for correction of HVI. All of the patients had other forefoot deformities which were corrected at the same time. Eight of these were revision procedures of prior forefoot operations. The length of follow-up was determined by the associated procedures with a minimum follow-up of 4 months. RESULTS: The preoperative hallux valgus interphalangeus angle averaged 16 degrees of valgus (range 7-32 degrees) and was corrected to an average of 2 degrees of valgus (range 5 degrees valgus to 5 degrees varus). All of the patients were satisfied with the postoperative appearance and function of the first toe. Because of simultaneous correction of numerous other forefoot problems, it was not possible to specifically isolate or evaluate the effects and benefits of this osteotomy using outcomes measures. There was one intraoperative complication resulting in a fracture extending into the adjacent IP joint. CONCLUSIONS: Correction of an HVI deformity can be achieved with an osteotomy at the distal end of the proximal phalanx. This was a safe technique with few complications and with good results in terms of both correction and patient satisfaction. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 27672061 TI - Oncological outcomes of function-preserving gastrectomy for early gastric cancer: a multicenter propensity score matched cohort analysis comparing pylorus preserving gastrectomy versus conventional distal gastrectomy. AB - OBJECTIVE: This study aimed to clarify the oncological safety of pylorus preserving gastrectomy (PPG) compared with conventional distal gastrectomy (DG). METHODS: From three institutions specializing in cancer, the medical records for a cohort of 2898 consecutive patients who had undergone DG (n = 2208) or PPG (n = 690) for clinical stage I gastric cancer between January 2006 and December 2012 were analyzed. A propensity score for each patient was estimated on the basis of 38 preoperative clinical and tumor-related factors. After propensity score matching had been done, 1004 patients (502 DG patients, 502 PPG patients) were included in the analysis. The overall survival, relapse-free survival, and occurrence of secondary gastric cancer were then compared. The median observation period was 48.6 months (range 1-109.8 months). RESULTS: The 5-year overall survival rate was 98.4 % for the PPG group and 96.6 % for the DG group (hazard ratio 0.48, 95 % confidence interval 0.21-1.09, P = 0.07). The 3-year relapse free survival rate was 99.5 % for the PPG group and 98.0 % for the DG group (hazard ratio 0.39, 95 % confidence interval 0.12-1.33, P = 0.12). Postoperative secondary gastric cancer was encountered in eight patients (1.6 %) in the PPG group and four patients (0.8 %) in the DG group. No significant differences in either overall survival, relapse-free survival, or the occurrence of secondary gastric cancer were observed between the two groups. CONCLUSIONS: Given the adequate estimation of the clinical tumor stage, the oncological safety of PPG for clinical T1N0 gastric cancer in the middle portion of the stomach was comparable to that of DG. PMID- 27672064 TI - Ethnic differences in coronary plaque and epicardial fat volume quantified using computed tomography. AB - Epidemiological studies observed a higher prevalence of coronary atherosclerosis in South Asians when compared to Caucasians, but quantitative computed tomography differences in aggregate plaque volume (APV) and epicardial fat volume (EFV) between South Asians, Southeast or East Asians (SEEAs) and Caucasians remain unknown. We aimed to compare APV and EFV quantified on computed-tomographic coronary-angiography (CTCA) between South Asian, SEEA and Caucasian populations residing in Australia. Age, gender and body-mass-index matched subjects from three ethnic groups who underwent clinically indicated 320-detector CTCA were retrospectively analysed. Percentage APV in the first 5 cm of the left anterior descending artery (LAD) and EFV were quantified using dedicated software (Vital Images, USA). One-hundred-and-fifty subjects (average age = 57.7 years, 56 % male, n = 50 in each ethnic group) were analysed. Mean LAD percentage APV was highest in South Asians (44.5 +/- 8.4 % vs. 37.5 +/- 6.5 % in SEEAs and 39.5 +/- 6.4 % in Caucasians, P = 0.00001). South Asian ethnicity predicted LAD APV above traditional risk factors on multivariate analysis (P = 0.000002). EFV was significantly higher in both South Asians (103.2 +/- 41.7 cm3 vs. 85.8 +/- 39.4 cm3, P = 0.035) and SEEAs (110.8 +/- 36.9 cm3 vs. 85.8 +/- 39.4 cm3, P = 0.001) when compared with Caucasians. In this cohort LAD percentage APV and EFV, as quantified on CTCA, differs between South Asians, SEEA and Caucasian populations, with higher LAD APV observed in South Asians and lower EFV in Caucasians. Atherosclerotic volume in LAD was best predicted by South Asian ethnicity above traditional risk factors and EFV. Further research is required to establish whether APV and EFV quantification can improve cardiac risk prediction in the South Asian population. PMID- 27672065 TI - Balloon pulmonary angioplasty improves interventricular dyssynchrony in patients with inoperable chronic thromboembolic pulmonary hypertension: a cardiac MR imaging study. AB - To use cardiac magnetic resonance imaging (MRI) to investigate the effect of balloon pulmonary angioplasty (BPA) on interventricular dyssynchrony and its associations with ventricular interaction, which impairs LV function in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). This prospective observational study was approved by our institutional review board. Cardiac MRI and right heart catheterization were conducted before BPA sessions and at the follow up after BPA in 20 patients with CTEPH. We measured right ventricular (RV) and left ventricular (LV) end-diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using MRI. For the LV and RV free walls, the time to peak (Tpeak) of circumferential strain was calculated as a parameter for interventricular dyssynchrony. Following BPA, the RV-EDV and -ESV were significantly decreased, and the RVEF was significantly increased. Conversely, BPA led to significantly increased LV EDV and SV without changing LVESV. The left-to-right free wall delay (L-R delay) in Tpeak strain decreased from 105 +/- 44 ms to 47 +/- 67 ms (p < 0.001). Increased LV EDV (r = 0.65, p < 0.01), SV (r = 0.74, p < 0.001) and 6-minute walk distance (6MWD) (r = 0.54, p < 0.05) were correlated to the reduction in L-R delay. In patients with inoperable CPEPH, BPA improved interventricular dyssynchrony, which was strongly associated with increased SV and 6MWD. The assessment of interventricular dyssynchrony using cardiac MRI has an important role in evaluating ventricular interaction, which reduces LVSV and exercise tolerance. PMID- 27672066 TI - Persons with allergy symptoms use alternative medicine more often. AB - INTRODUCTION: The aim of the study is to indicate the relation between the use of alternative medicine and the occurrence of allergic diseases in the Polish population of adults in the age of 20-44 years. Moreover the additional aim of the study is to define the relation between the sex, age and place of living and the use of alternative medicine. MATERIAL AND METHODS: The data from the project Epidemiology of Allergic Diseases in Poland (ECAP) has been used for analysis. This project was a continuation of the European Community Respiratory Health Survey II. The questions on alternative medicine were asked to the group of 4671 respondents in the age of 20-44 years. Additionally outpatient tests were performed in order to confirm the diagnosis of allergic diseases. RESULTS: The total of 22.2% of respondents that participated in the study have ever used alternative medicine (n = 4621). A statistically significant relation between the use of alternative medicine and declaration of allergic diseases and asthma symptoms has been demonstrated (p < 0.001). No statistically significant relation between the use of alternative medicine by persons diagnosed by a doctor with any form of asthma or seasonal allergic rhinitis (p > 0.05) has been demonstrated. CONCLUSIONS: The occurrence of allergic diseases and asthma influences the frequency of alternative medicine use. However the frequency of alternative medicine use does not depend on allergic disease or asthma being confirmed by a doctor. PMID- 27672067 TI - Effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in India. AB - INTRODUCTION: The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. MATERIAL AND METHODS: 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. RESULTS: The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. CONCLUSIONS: The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control. PMID- 27672069 TI - The incidence of tuberculosis transmission among family members and outside households. AB - INTRODUCTION: The risk of Mycobacterium tuberculosis complex (MTBC) infection is correlated with the concentration of infectious particles and exposure time. In closed populations, healthy people staying in very frequent, close and prolonged contact with a smear-positive person, become infected and represent another link in the chain of transmission of the disease. Therefore, in the fight against tuberculosis, an important element is quick identification of the patient and potentially infected people from his environment. In epidemiological investigation of tuberculosis (TB), family members are brought under special control as they are particularly exposed to transmission of infectious diseases. MATERIAL AND METHODS: The study included 150 patients with bacteriologically confirmed tuberculosis who were members of 59 families. In the years 2003-2013 this population represented all TB cases detected in Poland in a family environment.Three PCR-based genotyping methods: spoligotyping, IS6110-Mtb1-Mtb2 PCR and MIRU-VNTR typing were used. RESULTS: Of 150 patients, 138 could be assigned to intra-household transmission on the basis of identical DNA fingerprints upon a combined typing approach. For 12 patients in 6 households, the M. tuberculosis isolates were clearly distinct in individual analysis - IS6110-Mtb1-Mtb2 PCR, spoligotyping or MIRU-VNTR typing or in three genotyping methods, suggesting that these patients were infected by the sources in the community. CONCLUSIONS: The analysis confirmed the transmission of tuberculosis among members of 53 families. In the remaining 6 families the source of infection were people outside the households. In all families with young children, strains isolated from them have identical DNA patterns as strains obtained from their adult caregivers. To confirm the transmission of TB in the study population of patients, epidemiological analysis required the addition of a genotyping methods characterised by high discriminatory power. PMID- 27672068 TI - Centrilobular nodules in high resolution computed tomography of the lung in IPAH patients - preliminary data concerning clinico-radiological correlates. AB - INTRODUCTION: Inhomogeneity of lung attenuation pattern is observed in high resolution chest computed tomography (HRCT) in some IPAH patients despite lack of interstitial lung disease. Such radiological changes are described either as ill defined centrilobular nodules (CN) or as focal ground glass opacities (FGGO). There is no consensus in the literature, whether they indicate the distinct type of IPAH, or pulmonary venoocclusive disease (PVOD) with subtle radiological changes. Thus the aim of the present pilot study was to assess the frequency and clinical significance of inhomogenic lung attenuation pattern in IPAH. MATERIAL AND METHODS: 52 IPAH patients (38 females, 14 males, mean age 41 years +/- 15 years), entered the study. All available chest CT scans were reviewed retrospectively by the experienced radiologist, not aware about the clinical data of the patients. RESULTS: CN were found in 10 patients (19%), FGGO - in 12 patients (23%). No lymphadenopathy or interlobular septal thickening suggestive of PVOD were found. The significant differences between CN and the remaining patients included: lower mean age - 31 and 43.5 years, (p = 0.02), lack of persistent foramen ovale (PFO) - 0% and 43% (p = 0.03), and higher mean right atrial pressure (mRAP) - 12.5 mm Hg and 7.94 mm Hg (p = 0.01). No significant survival differences were observed between the groups of CN, FGGO and the remaining patients. CONCLUSION: Centrilobular nodules in IPAH were combined with lack of PFO, higher mRAP and younger age of patients. PMID- 27672070 TI - Musculosceletal tuberculosis with involvement of tendon sheaths and formation of synovial cyst. AB - Due to an increasing amount of patients on immunosuppressive treatment, the number of tuberculosis (TB) of atypical course and extrapulmonary tuberculosis cases increase. Locomotor system is a place of every fifth case of extrapulmonary TB. Because of lack of characteristic symptoms, as well as rare co-occurrence of active lung lesions in radiological imaging, proper diagnosis is hard to establish. We present a case of patient on immunosuppressive therapy due to myositis, in whom we diagnosed musculoskeletal tuberculosis in form of involvement of tendon sheath and formation of synovial cyst. PMID- 27672071 TI - Hemoptysis in a patient with multifocal primary pulmonary angiosarcoma. AB - Primary pulmonary angiosarcoma (PPA) is a rare tumour arising from arterial or venous pulmonary vessels of various size. It is characterized by aggressive course and poor prognosis. The early diagnosis is difficult due to diverse clinical and radiological manifestations. We present a case report of 70 year-old man, active cigarette-smoker, with a 2-month history of non-massive hemoptysis. The thorax CT revealed several solid pulmonary nodules surrounded by areas of ground glass opacity. As bronchoscopy failed to deliver adequate tissue samples, video assisted thoracic surgery (VATS) with pleura and lung biopsy was necessary. Histopathological findings were consistent with pulmonary angiosarcoma. Since no extrapulmonary lesions were demonstrated, the final diagnosis of primary pulmonary angiosarcoma was made. The patient died three months after the onset of symptoms. Our case report highlights that differential diagnosis in patients with hemoptysis and pulmonary nodules should include primary pulmonary sarcoma. PMID- 27672072 TI - The role of the TGF-SMAD signalling pathway in the etiopathogenesis of severe asthma. AB - Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling. PMID- 27672073 TI - Obstructive sleep apnea syndrome and hypothyroidism - merely concurrence or causal association? AB - The prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) ranges from 4 to 7% in men and from 2 to 5% in women. Its deleterious consequences such as traffic accidents, cardiovascular complications increasing morbidity and mortality, make it a major health problem. Apart from obesity (a major risk factor for OSAHS), hypothyroid patients are prone to reveal this phenotype. Although hypothyroidism seems an acknowledged risk factor for OSAHS, some authors report the lack of clinically relevant association. The argument partly depends on the increased prevalence of hypothyroidism in OSAHS patients, but the epidemiological data is limited and somehow inconsistent; even less is known about sub-clinical hypothyroidism in OSAHS patients. Even if frequency of overt and sub-clinical hypothyroidism in OSAHS patients is comparable to the general population, screening for it seems beneficial, as hormone replacement therapy may improve sleep disordered breathing. Unfortunately, this favorable outcome was found only in a few studies with limited number of patients with hypothyroidism. Yet, despite the lack of international guidelines and no large multicentre studies on the topic available, we think that TSH screening might prove beneficial in vast majority of OSAHS patients. PMID- 27672074 TI - Margaret McCartney: Breaking down the silo walls. PMID- 27672075 TI - Haemoproteus infection status of collared flycatcher males changes within a breeding season. AB - In ecological studies of haemosporidian parasites, prevalence is typically considered as a stable attribute. However, little is known about the possible within-host dynamics of these parasites that may originate from environmental fluctuations, parasite life cycles and the ability of hosts to suppress or clear infection. We sampled the blood of male collared flycatchers Ficedula albicollis twice within a breeding season and investigated the determinants of initial infection status and change in infection status. We found that older males tended to be initially more infected at courtship. Change in infection status was unrelated to male traits, but a widespread disappearance of Haemoproteus pallidus infection from the blood was detected between courtship and nestling rearing. The probability of change in infection status increased with the time elapsed between sampling occasions. This suggests that the disappearance of infection from the blood was due to either an active parasite suppression mechanism or the beginning of the latent phase in the parasite life cycle. Initial infection status or disappearance of infection from the blood showed no correlation with breeding success. These results show that H. pallidus infection status and thus prevalence are dynamically changing attributes and this has widespread practical and ecological implications. PMID- 27672076 TI - Are atherosclerotic risk factors associated with a poor prognosis in patients with hyperuricemic acute heart failure? The evaluation of the causal dependence of acute heart failure and hyperuricemia. AB - Atherosclerosis induces the elevation of uric acid (UA), and an elevated UA level is well known to lead to a poor prognosis in patients with acute heart failure (AHF). However, the prognostic value of atherosclerotic risk factors in hyperuricemic AHF patients remains to be elucidated. The data from 928 patients who were admitted to the intensive care unit (ICU) at Nippon Medical School Chiba Hokusoh Hospital between January 2001 and December 2014, and whose serum UA levels were measured were screened. A total of 394 AHF patients with hyperuricemia were enrolled in this study. The patients were assigned to a low risk group (<=1 atherosclerosis risk factor) and a high-risk group (>=2 atherosclerosis risk factors) according to their number of risk factors. The patients in the low-risk group were more likely to have dilated cardiomyopathy, clinical scenario 3 than those in the high-risk group. The serum total bilirubin, blood urea nitrogen, C-reactive protein, and brain-type natriuretic peptide levels were significantly higher in the low-risk group than the high-risk group (p < 0.001, p = 0.005, p = 0.003, and p = 0.008, respectively). A multivariate Cox regression model revealed that the number of risk factors (number = 1, HR (hazard ratio) 0.243, 95 % CI 0.096-0.618, p = 0.003; number = 2, HR 0.253, 95 % CI 0.108-0.593, p = 0.002; number >=3, HR 0.209, 95 % CI 0.093-0.472, p < 0.001), eGFR (per 1.0 mmol/l increase) (HR 0.977, 95 % CI 0.961-0.994, p = 0.007), and serum UA level (per 1 mg/dl increase) (HR 1.270, 95 % CI 1.123-1.435, p < 0.001) was an independent predictor of 1-year mortality. The prognosis, including all cause death and HF events, was significantly poorer among the low-risk patients than among the high-risk patients. Atherosclerotic risk factors were not associated with a poor prognosis in patients with hyperuricemic AHF. PMID- 27672077 TI - Higher hemoglobin A1c levels are associated with impaired left ventricular diastolic function and higher incidence of adverse cardiac events in patients with nonischemic dilated cardiomyopathy. AB - We aimed to elucidate the relationship between glycated hemoglobin (HbA1c), cardiac systolic/diastolic function, and heart failure (HF) prognosis during guideline-directed medical therapy in patients with nonischemic dilated cardiomyopathy (NIDCM). We evaluated 283 hospitalized NIDCM patients, who were grouped according to baseline (BL) and 1-year (1Y) levels of HbA1c (<6.0, 6.0 6.9, and >=7.0 %). The primary endpoint was defined as either readmission for HF worsening or cardiac death. Approximately half of the patients had BL- or 1Y HbA1c >=6.0 % (31 % at BL, 34 % at 1Y had 6.0-6.9 %; 12 % at BL, 12 % at 1Y had >=7.0 %). The absolute value of left ventricular ejection fraction (LVEF) and its improvement during 1 year showed no significant difference among the 1Y-HbA1c groups (p = 0.273), whereas a lower absolute value and a more significant reduction in the early diastolic velocity of the mitral annulus (E a) were seen in the group with 1Y-HbA1c >=7.0 % (both p < 0.001). In multiple regression analysis, higher 1Y-plasma B-type natriuretic peptide and lower 1Y-Ea were independently associated with higher 1Y-HbA1c (both adjusted p < 0.05). The cumulative incidence of the primary endpoint was highest in the group with 1Y HbA1c >=7.0 % (log-rank p = 0.001). Multivariate analysis demonstrated that higher 1Y-HbA1c was independently associated with a higher incidence of the primary endpoint (adjusted p = 0.005). In conclusion, hyperglycemia during clinical follow-up is a risk factor for progression of concomitant LV abnormal relaxation, leading to poor HF prognosis in patients with NIDCM. PMID- 27672080 TI - Multichromic Bis-Axially Extended Perylene Chromophore with Schiff Bases: Synthesis, Characterization and Electrochemical Studies. AB - In the present paper a novel way of symmetric conjugation extension along molecular axes of perylene dianhydride chromophore has been devised to achieve lengthy delocalized electronic species exhibiting red shifted absorption and emission of UV-Visible radiations. During synthetic pathway free amino Schiff bases of novel aldehydes with 4-amino acetanilide have been condensed with perylene dianhydride in quinoline at high temperature. Bis perylene diimide Schiff bases (5a-e) have been synthesized which showed absorption lambdamax at 461-526 nm and emission at 525-550 nm. Structures of newly obtained compounds have been confirmed by 1H and 13C-NMR studies. Cyclic voltammetric analysis of these dyes exhibited oxidation and reduction peaks which provide indirect evidence for their potential utility as n-type material for sensitization of semiconductors in solar cells. LUMO and HOMO energy levels were found in the range of -4.21 to -5.20 and -6.75 to -7.57 eV, respectively. Graphical Abstract Multi chromic bis-axially extended perylene chromophore with Schiff bases, synthesis characterization and electrochemical studies. Ghulam Shabir, Aamer Saeed, Muhammad Arshad and Muhammad Zahid. PMID- 27672081 TI - Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation. AB - Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD. PMID- 27672078 TI - Efficacy of Treatment of Non-hereditary Angioedema. AB - Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients. PMID- 27672079 TI - Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation. AB - Transdermal drug delivery is a useful route of administration that avoids first pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162 nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p < 0.05) 2.4-3.4-fold increase in the absorption of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, or through, the skin. The TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery. PMID- 27672082 TI - Application of bacteriocin RC20975 in apple juice. AB - Alicyclobacillus acidoterrestris is one of the most spoilage-causing bacteria in fruit juices. In this paper, controlling A. acidoterrestris in apple juice by bacteriocin RC20975 was described. Twenty-one strains of A. acidoterrestris were used to investigate the activity spectrum of bacteriocin RC20975 in apple juice with the result that 16 strains were sensitive . The ratio of activity in apple juice to the activity in laboratory medium was 42%. The reduction of antimicrobial activity in apple juice might be due to problems related to its interaction with food components. Adsorption of bacteriocin RC20975 to A. acidoterrestris cells varied according to the strains and the testing conditions (pH and temperatures). In an acid environment (pH 3 and pH 5), the adsorption was higher than that of the neutral environment. Dynamic model of killing bacteria was built under the condition of different temperatures with the addition of bacteriocin. Electron microscopy examination of vegetative cells revealed substantial cell damage and bacterial lysis after bacteriocin treatment. Although the endospores could not be killed, the addition of bacteriocin RC20975 contributed to the reduction of the thermal resistance of A. acidoterrestris spores in apple juice. In sum, bacteriocin RC20975 was proved to have a good effect on killing A. acidoterrestris in apple juice. PMID- 27672083 TI - Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2+ Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis. AB - Awareness of the immunological underpinnings of host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed that infection with the rat tapeworm, Hymenolepis diminuta, used as a model helminth, or systemic delivery of worm antigen (HdAg) significantly reduced the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Extending these analyses, intraperitoneal injection of HdAg dose dependently suppressed dextran sodium sulfate (DSS)-induced colitis, and this was paralleled by reduced gamma interferon (IFN-gamma), interleukin-17 (IL-17), and tumor necrosis factor alpha (TNF-alpha) production and increased IL-10 production from mitogen-activated splenocytes. Treatment with HdAg resulted in a CCR2 dependent recruitment of CDllb+ F4/80+ Ly6Chi Gr-1lo monocyte-like cells into the peritoneum 24 h later that were predominantly programmed death ligand 1 (PD-L1) positive and CXCR2 negative. In vitro assays indicated that these cells were unable to suppress T cell proliferation but enhanced IL-10 and IL-4 production from activated T cells. Adoptive transfer of the HdAg-recruited monocytic cells into naive mice blocked DSS-induced colitis. These findings add to the variety of means by which treatment with parasitic helminth-derived antigens can ameliorate concomitant disease. A precise understanding of the mechanism(s) of action of HdAg and other helminth-derived antigens (and a parallel consideration of putative side effects) may lead to the development of novel therapies for human idiopathic disorders such as inflammatory bowel disease. PMID- 27672087 TI - Correction. PMID- 27672084 TI - Impact of Moderate Temperature Changes on Neisseria meningitidis Adhesion Phenotypes and Proteome. AB - Neisseria meningitidis, the meningococcus, bears the potential to cause life threatening invasive diseases, but it usually colonizes the nasopharynx without causing any symptoms. Within the nasopharynx, Neisseria meningitidis must face temperature changes depending on the ambient air temperature. Indeed, the nasopharyngeal temperature can be substantially lower than 37 degrees C, the temperature commonly used in experimental settings. Here, we compared the levels of meningococcal biofilm formation, autoaggregation, and cellular adherence at 32 degrees C and 37 degrees C and found a clear increase in all these phenotypes at 32 degrees C suggestive of a stronger in vivo colonization capability at this temperature. A comparative proteome analysis approach revealed differential protein expression levels between 32 degrees C and 37 degrees C, predominantly affecting the bacterial envelope. A total of 375 proteins were detected. Use of database annotation or the PSORTb algorithm predicted 49 of those proteins to be localized in the outer membrane, 21 in either the inner or outer membrane, 35 in the periplasm, 56 in the inner membrane, and 208 in the cytosol; for 6 proteins, no annotation or prediction was available. Temperature-dependent regulation of protein expression was seen particularly in the periplasm as well as in the outer and inner membranes. Neisserial heparin binding antigen (NHBA), NMB1030, and adhesin complex protein (ACP) showed the strongest upregulation at 32 degrees C and were partially responsible for the observed temperature-dependent phenotypes. Screening of different global regulators of Neisseria meningitidis suggested that the extracytoplasmic sigma factor sigmaE might be involved in temperature dependent biofilm formation. In conclusion, subtle temperature changes trigger adaptation events promoting mucosal colonization by meningococci. PMID- 27672088 TI - Correction. PMID- 27672085 TI - The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response. AB - Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a DeltabpdA phosphodiesterase mutant producing excess c-di GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the DeltabpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase DeltacgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, DeltabpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. PMID- 27672089 TI - Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project. AB - Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 +/- 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 +/- 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion. PMID- 27672090 TI - Initiation of erythropoiesis-stimulating agents and outcomes: a nationwide observational cohort study in anaemic chronic kidney disease patients. AB - Background: In 2012, new clinical guidelines were introduced for use of erythropoiesis-stimulating agents (ESA) in chronic kidney disease (CKD) patients, recommending lower haemoglobin (Hb) target levels and thresholds for ESA initiation. These changes resulted in lower blood levels in these patients. However, there is limited evidence on just when ESA should be initiated and the safety of a low Hb initiation policy. Methods: In this observational inception cohort study, Swedish, nephology-referred, ESA-naive CKD patients (n = 6348) were enrolled when their Hb dropped below 12.0 g/L, and they were followed for mortality and cardiovascular events. Four different ESA treatments were evaluated applying dynamic marginal structural models: (i) begin ESA immediately, (ii) begin ESA when Hb <11.0 g/dL, (iii) begin ESA when Hb <10.0 g/dL and (iv) never begin ESA in comparison with 'current practice' [the observed (factual) survival of the entire study cohort]. The adjusted 3-year survival following ESA begun over a range of Hb (from <9.0 to 12.0 g/dL) was evaluated, after adjustment for covariates at baseline and during follow-up. Results: Overall, 36% were treated with ESA. Mortality during follow-up was 33.4% of the ESA-treated and 27.9% of the non-treated subjects. The adjusted 3-year survival associated with ESA initiation improved for subjects with initial Hb <9.0 to 11 g/dL and then decreased again for those with Hb above 11.5 g/dL. Initiating ESA at Hb <11.0 g/dL and <10.0 g/dL was associated with improved survival compared with 'current practice' [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.79-0.89 and 0.90; 95% CI 0.86-0.94, respectively] and did not increase the risk of a cardiovascular event (HR 0.93; 95% CI 0.87-1.00). Conclusion: In non-dialysis patients with CKD, ESA initiation at Hb < 10.0-11.0 g/dL is associated with improved survival in patients otherwise treated according to guidelines. PMID- 27672091 TI - Identification of Tension Sensing Motif of Histone H3 in Saccharomyces cerevisiae and Its Regulation by Histone Modifying Enzymes. AB - To ensure genome stability during cell division, all chromosomes must attach to spindles emanating from the opposite spindle pole bodies before segregation. The tension between sister chromatids generated by the poleward pulling force is an integral part of chromosome biorientation. In budding yeast, the residue Gly44 of histone H3 is critical for retaining the conserved Shugoshin protein Sgo1p at the pericentromeres for monitoring the tension status during mitosis. Studies carried out in this work showed that Lys42, Gly44, and Thr45 of H3 form the core of a tension sensing motif (TSM). Similar to the previously reported G44S mutant, K42A, G44A, and T45A alleles all rendered cells unable to respond to erroneous spindle attachment, a phenotype suppressed by Sgo1p overexpression. TSM functions by physically recruiting or retaining Sgo1p at pericentromeres as evidenced by chromatin immunoprecipitation and by in vitro pulldown experiments. Intriguingly, the function of TSM is likely regulated by multiple histone modifying enzymes, including the histone acetyltransferase Gcn5p, and deacetylases Rpd3p and Hos2p Defects caused by TSM mutations can be suppressed by the expression of a catalytically inactive mutant of Gcn5p Conversely, G44S mutant cells exhibit prominent chromatin instability phenotype in the absence of RPD3 Importantly, the gcn5- suppressor restores the tension sensing function in tsm- background in a fashion that bypasses the need of stably associating Sgo1p with chromatin. These results demonstrate that the TSM of histone H3 is a key component of a mechanism that ensures faithful segregation, and that interaction with chromatin modifying enzymes may be an important part of the mitotic quality control process. PMID- 27672093 TI - Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA. AB - Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Galpha, GPR-1/2, and LIN-5 (Galphai/Pins/Mud, Galphai/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Galpha, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Galpha- and DLG-1 independent mechanism. PMID- 27672092 TI - A Plastic Vegetative Growth Threshold Governs Reproductive Capacity in Aspergillus nidulans. AB - Ontogenetic phases separating growth from reproduction are a common feature of cellular life. Long recognized for flowering plants and animals, early literature suggests this life-history component may also be prevalent among multicellular fungi. We establish the basis of developmental competence-the capacity to respond to induction of asexual development-in the filamentous saprotroph Aspergillus nidulans, describing environmental influences, including genotype-by-environment interactions among precocious mutants, gene expression associated with wild type and precocious competence acquisition, and the genetics of competence timing. Environmental effects are consistent with a threshold driven by metabolic rate and organism density, with pH playing a particularly strong role in determining competence timing. Gene expression diverges significantly over the competence window, despite a lack of overt morphological change, with differentiation in key metabolic, signaling, and cell trafficking processes. We identify five genes for which mutant alleles advance competence timing, including the conserved GTPase RasB (AN5832) and ambient pH sensor PalH (AN6886). In all cases examined, inheritance of competence timing is complex and non-Mendelian, with F1 progeny showing highly variable transgressive timing and dominant parental effects with a weak contribution from progeny genotype. Competence provides a new model for nutrient-limited life-cycle phases, and their elaboration from unicellular origins. Further work is required to establish the hormonal and bioenergetic basis of the trait across fungi, and underlying mechanisms of variable inheritance. PMID- 27672094 TI - Joint Prediction of the Effective Population Size and the Rate of Fixation of Deleterious Mutations. AB - Mutation, genetic drift, and selection are considered the main factors shaping genetic variation in nature. There is a lack, however, of general predictions accounting for the mutual interrelation between these factors. In the context of the background selection model, we provide a set of equations for the joint prediction of the effective population size and the rate of fixation of deleterious mutations, which are applicable both to sexual and asexual species. For a population of N haploid individuals and a model of deleterious mutations with effect s appearing with rate U in a genome L Morgans long, the asymptotic effective population size (Ne) and the average number of generations (T) between consecutive fixations can be approximated by [Formula: see text] and [Formula: see text] The solution is applicable to Muller's ratchet, providing satisfactory approximations to the rate of accumulation of mutations for a wide range of parameters. We also obtain predictions of the effective size accounting for the expected nucleotide diversity. Predictions for sexual populations allow for outlining the general conditions where mutational meltdown occurs. The equations can be extended to any distribution of mutational effects and the consideration of hotspots of recombination, showing that Ne is rather insensitive and not proportional to changes in N for many combinations of parameters. This could contribute to explain the observed small differences in levels of polymorphism between species with very different census sizes. PMID- 27672095 TI - Trs33-Containing TRAPP IV: A Novel Autophagy-Specific Ypt1 GEF. AB - Ypt/Rab GTPases, key regulators of intracellular trafficking pathways, are activated by guanine-nucleotide exchange factors (GEFs). Here, we identify a novel GEF complex, TRAPP IV, which regulates Ypt1-mediated autophagy. In the yeast Saccharomyces cerevisiae, Ypt1 GTPase is required for the initiation of secretion and autophagy, suggesting that it regulates these two distinct pathways. However, whether these pathways are coordinated by Ypt1 and by what mechanism is still unknown. TRAPP is a conserved modular complex that acts as a Ypt/Rab GEF. Two different TRAPP complexes, TRAPP I and the Trs85-containing TRAPP III, activate Ypt1 in the secretory and autophagic pathways, respectively. Importantly, whereas TRAPP I depletion copies Ypt1 deficiency in secretion, depletion of TRAPP III does not fully copy the autophagy phenotypes of autophagy specific ypt1 mutations. If GEFs are required for Ypt/Rab function, this discrepancy implies the existence of an additional GEF that activates Ypt1 in autophagy. Trs33, a nonessential TRAPP subunit, was assigned to TRAPP I without functional evidence. We show that in the absence of Trs85, Trs33 is required for Ypt1-mediated autophagy and for the recruitment of core-TRAPP and Ypt1 to the preautophagosomal structure, which marks the onset of autophagy. In addition, Trs33 and Trs85 assemble into distinct TRAPP complexes, and we term the Trs33 containing autophagy-specific complex TRAPP IV. Because TRAPP I is required for Ypt1-mediated secretion, and either TRAPP III or TRAPP IV is required for Ypt1 mediated autophagy, we propose that pathway-specific GEFs activate Ypt1 in secretion and autophagy. PMID- 27672097 TI - Working-for-Food Behaviors: A Preclinical Study in Prader-Willi Mutant Mice. AB - Abnormal feeding behavior is one of the main symptoms of Prader-Willi syndrome (PWS). By studying a PWS mouse mutant line, which carries a paternally inherited deletion of the small nucleolar RNA 116 (Snord116), we observed significant changes in working-for-food behavioral responses at various timescales. In particular, we report that PWS mutant mice show a significant delay compared to wild-type littermate controls in responding to both hour-scale and seconds-to minutes-scale time intervals. This timing shift in mutant mice is associated with better performance in the working-for-food task, and results in better decision making in these mutant mice. The results of our study reveal a novel aspect of the organization of feeding behavior, and advance the understanding of the interplay between the metabolic functions and cognitive mechanisms of PWS. PMID- 27672098 TI - A rare but morbid neurosurgical target: petrous aneurysms and their endovascular management in the stent/flow diverter era. AB - BACKGROUND/OBJECTIVE: The rarity of petrous internal carotid artery (ICA) aneurysms has largely precluded analyses of their presentation and management in case series format. METHODS: We performed a retrospective analysis of our endovascular database of patients treated from January 2001 to May 2016 to identify patients with petrous ICA aneurysms. We evaluated the treatment approach and results for patients managed in the era of dedicated intracranial stents and flow diverters, noting clinical and angiographic results. RESULTS: Our database search identified 10 patients with petrous ICA aneurysms. Six aneurysms were managed in the era of dedicated intracranial stents and flow diverters. Two patients presented with cranial nerve palsies, two with incidental but enlarging aneurysms that had completely eroded through the petrous bone, one with transient ischemic attacks, and one with pulsatile tinnitus. Five aneurysms were large and one was small but symptomatic. In three cases the aneurysm was treated by flow diversion with adjunctive coiling; two patients with at least 4-month follow-up had complete occlusion of their aneurysm and significant improvement of mass effect symptoms. In one case the aneurysm was treated with balloon-assisted coiling with resultant near-complete occlusion. In two cases, prior to the introduction of flow diverters, the aneurysm was treated via stent-assisted coiling with resultant near-complete obliteration; one patient had resolution of pretreatment pulsatile tinnitus. There were no intraprocedural or postprocedural complications; no patients underwent retreatment. CONCLUSIONS: Endovascular treatment of large or symptomatic petrous ICA aneurysms, in the era of flow diversion, is associated with excellent angiographic and clinical outcomes. PMID- 27672096 TI - The Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes. AB - Mutation accumulation (MA) experiments employ the strategy of minimizing the population size of evolving lineages to greatly reduce effects of selection on newly arising mutations. Thus, most mutations fix within MA lines independently of their fitness effects. This approach, more recently combined with genome sequencing, has detailed the rates, spectra, and biases of different mutational processes. However, a quantitative understanding of the fitness effects of mutations virtually unseen by selection has remained an untapped opportunity. Here, we analyzed the fitness of 43 sequenced MA lines of the multi-chromosome bacterium Burkholderia cenocepacia that had each undergone 5554 generations of MA and accumulated an average of 6.73 spontaneous mutations. Most lineages exhibited either neutral or deleterious fitness in three different environments in comparison with their common ancestor. The only mutational class that was significantly overrepresented in lineages with reduced fitness was the loss of the plasmid, though nonsense mutations, missense mutations, and coding insertion deletions were also overrepresented in MA lineages whose fitness had significantly declined. Although the overall distribution of fitness effects was similar between the three environments, the magnitude and even the sign of the fitness of a number of lineages changed with the environment, demonstrating that the fitness of some genotypes was environmentally dependent. These results present an unprecedented picture of the fitness effects of spontaneous mutations in a bacterium with multiple chromosomes and provide greater quantitative support for the theory that the vast majority of spontaneous mutations are neutral or deleterious. PMID- 27672099 TI - Spine Metastasis Practice Patterns among Korean, Chinese, and Japanese Radiation Oncologists: A Multinational Online Survey Study. AB - This online survey of practising radiation oncologists from Korea, China and Japan was conducted to investigate the current practices in radiotherapy (RT) for spine metastasis and to compare these practices across the three countries. The questionnaire included nine general information questions and two clinical scenarios (representing 'typical' and 'good' prognosis spine metastasis), with seven questions for each scenario. An anonymous web-based survey using Google Docs(r) was undertaken from 2 September 2014 to 9 April 2015. A total of 54 Korean, 107 Chinese and 104 Japanese radiation oncologists participated in the study. The first scenario involved a typical case of spine metastasis (~25% expected 1-year survival rate), and the preferred fractionation scheme was 10 fractions of 3 Gy, though the pattern was slightly different in each country. The second scenario involved a good prognosis case (>50% expected 1-year survival rate), and 10 fractions of 3 Gy was the preferred practice in all three countries (however, use of a larger fraction dose with a smaller fraction number was more common in Korea). A more conformal RT technique was more prominent in China and Korea, especially for patients with a good prognosis. Avoidance of reirradiation was notable in China. In summary, a preference for multiple fractionation in RT for spine metastasis was observed in the majority of Korean, Chinese and Japanese radiation oncologists, although there were slight differences in practice preferences, especially for patients with a favorable prognosis. PMID- 27672100 TI - DNA damage response induces structural alterations in histone H3-H4. AB - Synchrotron-radiation circular-dichroism spectroscopy was used to reveal that the DNA damage response induces a decrement of alpha-helix and an increment of beta strand contents of histone H3-H4 extracted from X-ray-irradiated human HeLa cells. The trend of the structural alteration was qualitatively opposite to that of our previously reported results for histone H2A-H2B. These results strongly suggest that histones share roles in DNA damage responses, particularly in DNA repair processes and chromatin remodeling, via a specific structural alteration of each histone. PMID- 27672103 TI - Treatment of a giant inguinal hernia using transabdominal pre-peritoneal repair. AB - We present the case of a male Japanese patient with a giant inguinal hernia that extended to his knees while standing. A transabdominal pre-peritoneal (TAPP) repair was performed under general anesthesia. Complete reduction of the contents of the hernia was achieved within 2 h 50 min. A blood loss of approximately 700 ml was noted. The patient was discharged from the hospital on post-operative Day 12, with no recurrence of the hernia 6 months post-surgery. Factors contributing to the successful outcomes included preparation of several reduction methods before surgery, use of a large size mesh and implementation of pre-operative measures to prevent abdominal compartment syndrome. Further studies are required to evaluate the feasibility of laparoscopic repair in the management of giant inguinal hernia. PMID- 27672101 TI - Glycyrrhetinic acid alleviates radiation-induced lung injury in mice. AB - Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-beta1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-beta1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-beta1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-beta1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-beta1/Smads signaling pathway. PMID- 27672104 TI - A rare presentation of breast cancer: near obstructing rectal mass and gastric outlet obstruction. AB - Breast cancer metastasizes to the gastrointestinal (GI) tract are exceedingly rare. The low incidence and vague presentation of GI metastasizes often cause delay in diagnosis and treatment. Here, we present a case of metastatic breast cancer causing gastric outlet obstruction and rectal obstruction. PMID- 27672105 TI - Port-site implantation of Type A Masaoka Stage I thymoma after video-assisted thoracic surgery: a case report. AB - A 60-year-old woman was referred to our hospital with an anterior mediastinal tumor measuring 3.5 cm in diameter on computed tomography (CT). We performed tumor resection by video-assisted thoracic surgery (VATS) with three ports. The final diagnosis was Type A Masaoka Stage I thymoma. On follow-up CT performed 36 months after the operation, two pleural tumors were detected at the port sites through which the forceps and ultrasonic scalpel had passed repeatedly during the operation. We therefore performed a second operation and enucleated the tumors while preserving the ribs. However, other tumor tissue was detected along the surgical marginal line during the pathological diagnosis after the operation. Surgeons should thus be aware that port-site recurrence can occur after VATS resection of Type A thymoma, despite its mild biological behavior. Wide resection of the chest wall is therefore recommended for operations of port-site recurrence after VATS thymectomy. PMID- 27672102 TI - Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene: In Vivo and In Vitro Evidences of a Cell Replication Process. AB - Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2. We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age. Interestingly, ELOVL2 hypermethylation was not found in tissues with very low replication rate. We demonstrated that ELOVL2 hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra individual hypermethylation of ELOVL2 and FHL2 in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, ELOVL2 methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that ELOVL2 methylation is a marker of cell divisions occurring during human aging. PMID- 27672106 TI - The burgeoning antibody landscape. PMID- 27672107 TI - Somatic mutation, copy number and transcriptomic profiles of primary and matched metastatic estrogen receptor-positive breast cancers. AB - BACKGROUND: Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy. MATERIALS AND METHODS: A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material. According to the availability of tumor material, samples were characterized using a 120 mutational hotspot qPCR, a 29 gene copy number aberrations (CNA) and a 400 gene expression panels. ESR1 mutations were assayed by droplet digital PCR. Molecular alterations were correlated with overall survival (OS) using the Cox proportional hazards regression models. RESULTS: The median follow-up was 6.4 years (range 0.5-26.6 years). Genomic analysis of P tumors revealed somatic mutations in PIK3CA, KRAS, AKT1, FGFR3, HRAS and BRAF at frequencies of 41%, 6%, 5%, 2%, 1% and 2%, respectively, and CN amplification of CCND1, ZNF703, FGFR1, RSF1 and PAK1 at 23%, 19%, 17%, 12% and 11%, respectively. Mutations and CN amplifications were largely concordant between P and matched M (>84%). ESR1 mutations were found in 10.8% of the M but none of the P. Thirteen genes, among which ESR1, FOXA1, and HIF1A, showed significant differential expression between P and M. In P, the differential expression of 18 genes, among which IDO1, was significantly associated with OS (FDR < 0.1). CONCLUSIONS: Despite the large concordance between P and matched M for the evaluated molecular alterations, potential actionable targets such as ESR1 mutations were found only in M. This supports the importance of characterizing the M disease. Other targets we identified, such as HIF1A and IDO1, warrant further investigation in this patient population. PMID- 27672109 TI - Chemoprevention of hepatocellular carcinoma in people affected by hepatitis C virus: what changes does the introduction of direct-acting antiviral agents make? PMID- 27672110 TI - Reply to 'Chemoprevention of hepatocellular carcinoma in people affected by hepatitis C virus: what changes does the introduction of direct-acting antiviral agents make?'. PMID- 27672111 TI - A Simplified Strategy for Introducing Genetic Variants into Drosophila Compound Autosome Stocks. AB - Drosophila stocks bearing compound chromosomes, single molecules of DNA that carry the genomic complement of two chromosomes, are useful tools for studying meiosis and mitosis. However, these stocks cannot easily be crossed to stocks with regular chromosomes, due to the lethality of the resulting whole-chromosome aneuploidy. This prevents the examination of interesting genetic variants in a compound chromosome background. Methods to circumvent this difficulty have included the use of triploid females or nondisjunction (caused by either cold induced microtubule depolymerization or meiotic mutants). Here, we present a new approach for crossing compound chromosomes that takes advantage of the nonhomologous segregations that result when multiple chromosomes in the same genome are prevented from meiotic crossing over by heterozygosity for balancer chromosomes. This approach gives higher yields of the desired progeny in fewer generations of crossing. Using this technique, we have created and validated stocks carrying both a compound-X and compound-2, as well as compound-2 stocks carrying the meiotic mutant nod. PMID- 27672108 TI - First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas. AB - BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1-1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [(18)F] fluorodeoxyglucose positron emission tomography ((18)FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. RESULTS: Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced (18)FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. CONCLUSION: Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib exhibited dose-proportional pharmacokinetics and promising anti-tumor activity, particularly in patients with NHL. CLINICALTRIALSGOV: NCT00962611; https://clinicaltrials.gov/ct2/show/NCT00962611. PMID- 27672112 TI - Improvement of Predictive Ability by Uniform Coverage of the Target Genetic Space. AB - Genome-enabled prediction provides breeders with the means to increase the number of genotypes that can be evaluated for selection. One of the major challenges in genome-enabled prediction is how to construct a training set of genotypes from a calibration set that represents the target population of genotypes, where the calibration set is composed of a training and validation set. A random sampling protocol of genotypes from the calibration set will lead to low quality coverage of the total genetic space by the training set when the calibration set contains population structure. As a consequence, predictive ability will be affected negatively, because some parts of the genotypic diversity in the target population will be under-represented in the training set, whereas other parts will be over-represented. Therefore, we propose a training set construction method that uniformly samples the genetic space spanned by the target population of genotypes, thereby increasing predictive ability. To evaluate our method, we constructed training sets alongside with the identification of corresponding genomic prediction models for four genotype panels that differed in the amount of population structure they contained (maize Flint, maize Dent, wheat, and rice). Training sets were constructed using uniform sampling, stratified-uniform sampling, stratified sampling and random sampling. We compared these methods with a method that maximizes the generalized coefficient of determination (CD). Several training set sizes were considered. We investigated four genomic prediction models: multi-locus QTL models, GBLUP models, combinations of QTL and GBLUPs, and Reproducing Kernel Hilbert Space (RKHS) models. For the maize and wheat panels, construction of the training set under uniform sampling led to a larger predictive ability than under stratified and random sampling. The results of our methods were similar to those of the CD method. For the rice panel, all training set construction methods led to similar predictive ability, a reflection of the very strong population structure in this panel. PMID- 27672115 TI - Understanding disease mechanisms at the nanoscale: endothelial apoptosis and microparticles in COPD. PMID- 27672113 TI - The GATOR1 Complex Regulates Metabolic Homeostasis and the Response to Nutrient Stress in Drosophila melanogaster. AB - TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy. However, the precise role of GATOR1 in animal physiology remains largely undefined. Here, we characterize null mutants of the GATOR1 components nprl2, nprl3, and iml1 in Drosophila melanogaster We demonstrate that all three mutants have inappropriately high baseline levels of TORC1 activity and decreased adult viability. Consistent with increased TORC1 activity, GATOR1 mutants exhibit a cell autonomous increase in cell growth. Notably, escaper nprl2 and nprl3 mutant adults have a profound locomotion defect. In line with a nonautonomous role in the regulation of systemic metabolism, expressing the Nprl3 protein in the fat body, a nutrient storage organ, and hemocytes but not muscles and neurons rescues the motility of nprl3 mutants. Finally, we show that nprl2 and nprl3 mutants fail to activate autophagy in response to amino acid limitation and are extremely sensitive to both amino acid and complete starvation. Thus, in Drosophila, in addition to maintaining baseline levels of TORC1 activity, the GATOR1 complex has retained a critical role in the response to nutrient stress. In summary, the TORC1 inhibitor GATOR1 contributes to multiple aspects of the development and physiology of Drosophila. PMID- 27672114 TI - Reconstructing the Backbone of the Saccharomycotina Yeast Phylogeny Using Genome Scale Data. AB - Understanding the phylogenetic relationships among the yeasts of the subphylum Saccharomycotina is a prerequisite for understanding the evolution of their metabolisms and ecological lifestyles. In the last two decades, the use of rDNA and multilocus data sets has greatly advanced our understanding of the yeast phylogeny, but many deep relationships remain unsupported. In contrast, phylogenomic analyses have involved relatively few taxa and lineages that were often selected with limited considerations for covering the breadth of yeast biodiversity. Here we used genome sequence data from 86 publicly available yeast genomes representing nine of the 11 known major lineages and 10 nonyeast fungal outgroups to generate a 1233-gene, 96-taxon data matrix. Species phylogenies reconstructed using two different methods (concatenation and coalescence) and two data matrices (amino acids or the first two codon positions) yielded identical and highly supported relationships between the nine major lineages. Aside from the lineage comprised by the family Pichiaceae, all other lineages were monophyletic. Most interrelationships among yeast species were robust across the two methods and data matrices. However, eight of the 93 internodes conflicted between analyses or data sets, including the placements of: the clade defined by species that have reassigned the CUG codon to encode serine, instead of leucine; the clade defined by a whole genome duplication; and the species Ascoidea rubescens These phylogenomic analyses provide a robust roadmap for future comparative work across the yeast subphylum in the disciplines of taxonomy, molecular genetics, evolutionary biology, ecology, and biotechnology. To further this end, we have also provided a BLAST server to query the 86 Saccharomycotina genomes, which can be found at http://y1000plus.org/blast. PMID- 27672116 TI - Home-based rehabilitation for COPD using minimal resources: a randomised, controlled equivalence trial. AB - BACKGROUND: Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor. We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation. METHODS: A randomised controlled equivalence trial with 12 months follow-up. Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist. The primary outcome was change in 6 min walk distance (6MWD). RESULTS: We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80). Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI -3.3 to 40.7). At 12 months the CI did not exclude inferiority (-5.1 m, -29.2 to 18.9). Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, -0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, -2.0 to 2.1). The per-protocol analysis showed the same pattern of findings. Neither group maintained postrehabilitation gains at 12 months. CONCLUSIONS: This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation. Neither model was effective in maintaining gains at 12 months. Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation. TRIAL REGISTRATION NUMBER: NCT01423227, clinicaltrials.gov. PMID- 27672118 TI - Mortality of CAP reduced in the UK: is this enough? PMID- 27672119 TI - The pressure-dependent air leak after partial lung resection. PMID- 27672117 TI - Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. AB - RATIONALE: There is no consensus as to when treatment for idiopathic pulmonary fibrosis (IPF) should be initiated. Some physicians prefer not to treat patients with preserved lung volume. OBJECTIVE: To investigate whether patients with IPF and preserved lung volume receive the same benefit from nintedanib as patients with more impaired lung volume. METHODS: Post hoc subgroup analyses of pooled data from the two replicate phase III INPULSIS trials by baseline FVC % predicted (<=90%, >90%). RESULTS: At baseline, 274 patients had FVC >90% predicted and 787 patients had FVC <=90% predicted. In patients treated with placebo, the adjusted annual rate of decline in FVC was consistent between patients with FVC >90% predicted and FVC <=90% predicted (-224.6 mL/year and -223.6 mL/year, respectively). There was no statistically significant difference between these subgroups in the effect of nintedanib on annual rate of decline in FVC, change from baseline in St George's Respiratory Questionnaire total score or time to first acute exacerbation. In patients with baseline FVC >90% predicted and <=90% predicted, respectively, the adjusted annual rate of decline in FVC with nintedanib was -91.5 mL/year (difference vs placebo: 133.1 mL/year (95% CI 68.0 to 198.2)) and -121.5 mL/year (difference vs placebo: 102.1 mL/year (95% CI 61.9 to 142.3)). Adverse events associated with nintedanib were similar in both subgroups. CONCLUSIONS: Patients with IPF and preserved lung volume (FVC >90% predicted) have the same rate of FVC decline and receive the same benefit from nintedanib as patients with more impaired lung volume. TRIAL REGISTRATION NUMBER: NCT01335464 and NCT01335477. PMID- 27672120 TI - Mechanisms by which obesity impacts upon asthma. AB - Asthma, an inflammatory disease of the airways, is a common condition, currently affecting about 9% of adults. Obesity is another disease with high prevalence in adults, and asthma that develops in obese individuals appears to be distinct from other forms of asthma, in being particularly severe and difficult to control even with oral corticosteroids. Moreover, recent studies suggest that obesity may have a causal relationship with asthma. In this review, we discuss possible obesity driven metabolic and immunological pathways that might lead to asthma that is associated with obesity. Our understanding of the mechanisms that underlie this association will likely lead in the future to improved treatments for this significant unmet medical need. PMID- 27672122 TI - When patient-centred care is worth doing well: informed consent or shared decision-making. PMID- 27672121 TI - The effects of growing up on a farm on adult lung function and allergic phenotypes: an international population-based study. AB - RATIONALE: Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk. OBJECTIVES: To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood. METHODS AND MEASUREMENTS: The European Community Respiratory Health Survey II investigated ~10 201 participants aged 26-54 years from 14 countries, including participants' place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed. MAIN RESULTS: As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV1 (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation. CONCLUSIONS: This is the first study to report beneficial effects of growing up on a farm on adult FEV1. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment. PMID- 27672123 TI - Calibrating how doctors think and seek information to minimise errors in diagnosis. PMID- 27672128 TI - Case Reports for Laboratory Animals. PMID- 27672124 TI - Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial. AB - OBJECTIVES: This phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE). METHODS: Patients with active disease were randomised to placebo or PF-04236921 10 mg, 50 mg or 200 mg, subcutaneously, every 8 weeks with stable background therapy. SLE Responder Index (SRI-4; primary end point) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) were assessed at week 24. Post hoc analysis identified an enriched population based upon planned univariate analyses. RESULTS: 183 patients received treatment (placebo, n=45; 10 mg, n=45; 50 mg, n=47; 200 mg, n=46). The 200 mg dose was discontinued due to safety findings and not included in the primary efficacy analysis. The SRI-4 response rates were not significant for any dose compared with placebo; however, the BICLA response rate was significant for 10 mg (p=0.026). The incidence of severe flares was significantly reduced with 10 mg (n=0) and 50 mg (n=2) combined versus placebo (n=8; p<0.01). In patients with greater baseline disease activity (enriched population), the SRI-4 (p=0.004) and BICLA (p=0.012) response rates were significantly different with 10 mg versus placebo. Four deaths (200 mg, n=3; 10 mg, n=1) occurred. The most frequently reported adverse events included headache, nausea and diarrhoea. CONCLUSIONS: PF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE. Evidence of an effect with 10 mg was seen in a post hoc analysis. Safety was acceptable for doses up to 50 mg as the 200 mg dose was discontinued due to safety findings. TRIAL REGISTRATION NUMBER: NCT01405196; Pre-results. PMID- 27672126 TI - Reducing the nicotine content of combusted tobacco products sold in New Zealand. AB - Large reductions in nicotine content could dramatically reduce reinforcement from and dependence on cigarettes. In this article, we summarise the potential benefits of reducing nicotine in combusted tobacco and address some of the common concerns. We focus specifically on New Zealand because it may be ideally situated to implement such a policy. The available data suggest that, in current smokers, very low nicotine content (VLNC) cigarettes decrease nicotine exposure, decrease cigarette dependence, reduce the number of cigarettes smoked per day and increase the likelihood of contemplating, making and succeeding at a quit attempt. New smokers would almost certainly be exposed to far less nicotine as a result of smoking VLNC cigarettes and, consequently, would probably be less likely to become chronic, dependent, smokers. Many of the concerns about reducing nicotine including compensatory smoking, an exacerbation of psychiatric symptoms, the perception that VLNC cigarettes are less harmful, and the potential for a black market are either not supported by the available data, likely mitigated by other factors including the availability of nicotine-containing e-cigarettes, or unlikely to offset the potential benefit to public health. Although not all concerns have been addressed or can be a priori, the magnitude of the potential benefits and the growing evidence of relatively few potential harms should make nicotine reduction one of the centrepieces for discussion of how to rapidly advance tobacco control. Policies that aim to render the most toxic tobacco products less addictive could help New Zealand attain their goal of becoming smokefree by 2025. PMID- 27672125 TI - Contrasting expression pattern of RNA-sensing receptors TLR7, RIG-I and MDA5 in interferon-positive and interferon-negative patients with primary Sjogren's syndrome. AB - OBJECTIVE: The interferon (IFN) type I signature is present in over half of patients with primary Sjogren's syndrome (pSS) and associated with higher disease activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered as the main source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of patients with pSS. METHODS: Blood samples from 42 healthy controls (HC) and 115 patients with pSS were stratified according to their IFN type I signature. CD123+BDCA4+ pDCs and CD14+ monocytes were isolated from peripheral blood mononuclear cells (PBMCs). Genome-wide microarray analysis was conducted on sorted pDCs in a small sample set, followed by validation of differentially expressed genes of interest in pDCs and monocytes. RESULTS: We found an upregulation of endosomal toll-like receptor (TLR) 7, but not TLR9, in IFN-positive (IFNpos) pDCs (p<0.05) and monocytes (p=0.024). Additionally, the downstream signalling molecules MyD88, RSAD2 and IRF7 were upregulated, as were the cytoplasmic RNA-sensing receptors DDX58/retinoic acid inducible gene-I (RIG I) and IFIH1/melanoma differentiation associated gene-5 (MDA5). In vitro triggering of the TLR7-pathway in HC PBMCs induced upregulation of DDX58/RIG-I and IFIH1/MDA5, and downregulated TLR9. The upregulation of TLR7, its downstream signalling pathway, DDX58/RIG-I and IFIH1/MDA5 were confined to patients with IFN positive pSS. IFN-negative patients had a contrasting expression pattern-TLR7 normal, and decreased TLR9, RIG-I and MDA5. CONCLUSIONS: Here we conclude a contrasting expression pattern of the RNA-sensing receptors TLR7, RIG-I and MDA5 in pDCs and monocytes of patients with IFNpos pSS. This profile could explain the pathogenic IFN production and might reveal novel therapeutic targets in these patients. PMID- 27672129 TI - 15e Symposium ComTech. PMID- 27672130 TI - Recomendaciones para controles microbiologicos ambientales y de agua en un animalario. PMID- 27672131 TI - Trait coordination, mechanical behaviour and growth form plasticity of Amborella trichopoda under variation in canopy openness. AB - Understanding the distribution of traits across the angiosperm phylogeny helps map the nested hierarchy of features that characterize key nodes. Finding that Amborella is sister to the rest of the angiosperms has raised the question of whether it shares certain key functional trait characteristics, and plastic responses apparently widespread within the angiosperms at large. With this in mind, we test the hypothesis that local canopy openness induces plastic responses. We used this variation in morphological and functional traits to estimate the pervasiveness of trait scaling and leaf and stem economics. We studied the architecture of Amborella and how it varies under different degrees of canopy openness. We analyzed the coordination of 12 leaf and stem structural and functional traits, and the association of this covariation with differing morphologies. The Amborella habit is made up of a series of sympodial modules that vary in size and branching pattern under different canopy openness. Amborella stems vary from self-supporting to semi-scandent. Changes in stem elongation and leaf size in Amborella produce distinct morphologies under different light environments. Correlations were found between most leaf and stem functional traits. Stem tissue rigidity decreased with increasing canopy openness. Despite substantial modulation of leaf size and leaf mass per area by light availability, branches in different light environments had similar leaf area-stem size scaling. The sympodial growth observed in Amborella could point to an angiosperm synapomorphy. Our study provides evidence of intraspecific coordination between leaf and stem economic spectra. Trait variation along these spectra is likely adaptive under different light environments and is consistent with these plastic responses having been present in the angiosperm common ancestor. PMID- 27672133 TI - Quenching tank: Accidental drowning in hot quenching oil. AB - We describe an unusual case of drowning in fluid other than water in an industrial setting. A 26-year-old man was working in an industry which performs surface treatment of mechanical steel parts with quenching oil. He fell into the quenching oil (which was hot due to immersion of red hot metal parts), and as he was working alone in the particular section, there was a fatal outcome. A medico legal autopsy was performed. The causes of death were found to be multiple, with the association of drowning, extensive superficial burns and asphyxia due to laryngeal oedema. To our knowledge, it is the first report of drowning in hot quenching oil, and only nine previous observations of drowning in industrial environments have been reported in the international literature. Even though rare, these kinds of accidental deaths can be prevented in dangerous industries with proper precautions and strict adherence to standard operating procedures. PMID- 27672132 TI - Mechanism of three-component collision to produce ultrastable pRNA three-way junction of Phi29 DNA-packaging motor by kinetic assessment. AB - RNA nanotechnology is rapidly emerging. Due to advantageous pharmacokinetics and favorable in vivo biodistribution, RNA nanoparticles have shown promise in targeted delivery of therapeutics. RNA nanotechnology applies bottom-up assembly, thus elucidation of the mechanism of interaction between multiple components is of fundamental importance. The tendency of diminishing concern about RNA instability has accelerated by the finding of the novel thermostable three-way junction (3WJ) motif of the phi29 DNA-packaging motor. The kinetics of these three components, each averaging 18 nucleotides (nt), was investigated to elucidate the mechanism for producing the stable 3WJ. The three fragments coassembled into the 3WJ with extraordinary speed and affinity via a two-step reaction mechanism, 3WJb + 3WJc <-> 3WJbc + 3WJa <-> 3WJabc The first step of reaction between 3WJb and 3WJc is highly dynamic since these two fragments only contain 8 nt for complementation. In the second step, the 3WJa, which contains 17 nt complementary to the 3WJbc complex, locks the unstable 3WJbc complex into a highly stable 3WJ. The resulting pRNA-3WJ is more stable than any of the dimer species as shown in the much more rapid association rates and slowest dissociation rate constant. The second step occurs at a very high association rate that is difficult to quantify, resulting in a rapid formation of a stable 3WJ. Elucidation of the mechanism of three-component collision in producing the ultrastable 3WJ proves a promising platform for bottom-up assembly of RNA nanoparticles as a new class of anion polymers for material science, electronic elements, or therapeutic reagents. PMID- 27672134 TI - Anthropometric measures and prevalence trends in adolescents with coeliac disease: a population based study. AB - OBJECTIVES: To investigate the impact of coeliac disease (CD) diagnosis on anthropometric measures at late adolescence and to assess trends in the prevalence of diagnosed CD over time. DESIGN: A population based study. PATIENTS: Prior to enlistment, at the age of 17 years, most of the Israeli Jewish population undergoes a general health examination. Subjects' medical diagnoses are entered into a structured database. INTERVENTIONS: The enlistment database was thoroughly searched for CD cases between the years 1988 and 2015. Medical records of 2 001 353 subjects were reviewed. MAIN OUTCOME MEASURES: Anthropometric measures at the age of 17 years. RESULTS: Overall, 10 566 CD cases (0.53%) were identified and analysed. Median age at data ascertainment was 17.1 years (IQR, 16.9-17.4). Multivariable analysis demonstrated that boys with CD were leaner (Body Mass Index 21.2+/-3.7 vs 21.7+/-3.8, p=0.02) while girls with CD were shorter (161.5+/-6 cm vs 162.1+/-6 cm, p=0.017) than the general population. The prevalence of diagnosed CD increased from 0.5% to 1.1% in the last 20 years with a female predominance (0.64% vs 0.46%). CD prevalence was significantly lower in subjects of lower socioeconomic status and those of African, Asian and former Soviet Union origin. CONCLUSIONS: Adolescent boys with CD were leaner and girls with CD were shorter compared with the general population. However, the clinical relevance of the small differences suggests that when CD is diagnosed during childhood, final weight and height are not severely impaired. Our cohort reinforces the observed increase in diagnosed CD. PMID- 27672136 TI - Risk of venous thromboembolism in neuromyelitis optica patients hospitalized for acute relapse. AB - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. OBJECTIVE: To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. METHODS: Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. RESULTS: A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 ( p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. CONCLUSION: NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis. PMID- 27672135 TI - Early puberty in 11-year-old girls: Millennium Cohort Study findings. AB - OBJECTIVE: Early puberty in girls is linked to some adverse outcomes in adolescence and mid-life. We address two research questions: (1) Are socioeconomic circumstances and ethnicity associated with early onset puberty? (2) Are adiposity and/or psychosocial stress associated with observed associations? DESIGN: Longitudinal data on 5839 girls from the UK Millennium Cohort Study were used to estimate associations between ethnicity, family income, adiposity and psychosocial stress with a marker of puberty. MAIN OUTCOME MEASURE: Reported menstruation at age 11 years. RESULTS: All quoted ORs are statistically significant. Girls in the poorest income quintile were twice as likely (OR=2.1), and the second poorest quintile nearly twice as likely (OR=1.9) to have begun menstruation compared with girls in the richest income quintile. Estimates were roughly halved on adjustment for Body Mass Index and markers of psychosocial stress (poorest, OR=1.5; second poorest, OR=1.5). Indian girls were over 3 times as likely compared with whites to have started menstruation (OR=3.5) and statistical adjustments did not attenuate estimates. The raised odds of menstruation for Pakistani (OR=1.9), Bangladeshi (OR=3.3) and black African (OR=3.0) girls were attenuated to varying extents, from about a third to a half, on adjustment for income and adiposity. CONCLUSIONS: In contemporary UK, excess adiposity and psychosocial stress were associated with social inequalities in early puberty, while material disadvantage and adiposity were linked to ethnic inequalities in early puberty among girls. PMID- 27672137 TI - Personalised medicine for multiple sclerosis care. AB - Treatments with a range of efficacy and risk of adverse events have become available for the management of multiple sclerosis (MS). However, now the heterogeneity of clinical expression and responses to treatment pose major challenges to improving patient care. Selecting and managing the drug best balancing benefit and risk demands a new focus on the individual patient. Personalised medicine for MS is based on improving the precision of diagnosis for each patient in order to capture prognosis and provide an evidence-based framework for predicting treatment response and personalising patient monitoring. It involves development of predictive models involving the integration of clinical and biological data with an understanding of the impact of disease on the lives of individual patients. Here, we provide a brief, selective review of challenges to personalisation of the management of MS and suggest an agenda for stakeholder engagement and research to address them. PMID- 27672139 TI - Pharmacologic management of myelofibrosis. AB - Myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm characterized by abnormal hematopoiesis. Alterations to the Janus kinase-signal transducer and activator of transcription pathway result in dysregulation of gene transcription and cell proliferation. Patients with symptomatic myelofibrosis present with a variety of signs and symptoms including, but not limited to myelosuppression, marked splenomegaly, abdominal discomfort, fatigue, and blood transfusion dependence. Traditional myelosuppressive therapies including hydroxyurea, azacitidine, and cladribine aim to reduce constitutional symptoms and control the burden of disease. Immunomodulators can potentially reverse anemia associated with myelofibrosis, but are poorly tolerated by most patients. The novel Janus kinase 2 (JAK2) inhibitor, ruxolitinib, has demonstrated marked improvements to constitutional symptoms and splenomegaly. While survival benefit has not yet been demonstrated, continued research into pharmacologic management of myelofibrosis offers the promise of altering the course of disease progression. PMID- 27672140 TI - Impact of a primary care national policy on HIV screening in France: a longitudinal analysis between 2006 and 2013. AB - BACKGROUND: Early diagnosis of HIV infection is a major public health issue worldwide. In 2009, the French National Authority for Health (Haute Autorite de Sante) developed specific guidelines and recommended mass screening of 15-70-year olds across the general population. The guidelines were supported by communication directed at healthcare professionals, especially GPs. AIM: To assess the impact of the national mass screening policy on HIV testing. DESIGN AND SETTING: The study used data from the French National Health Insurance Fund database, from January 2006 to December 2013. Males and females aged 15-70 years, excluding HIV-positive individuals and pregnant females, were followed up throughout the 2006-2013 period. During the study period, 2 176 657 person-years and a total of 329 748 different individuals were followed up. METHOD: Standardised and non-standardised rates of HIV screening were calculated for each year; the impact of the policy was assessed using adjusted segmented regression analyses. RESULTS: Overall, annual HIV screening rates increased over the study period, from 4.2% (95% confidence interval [CI] = 4.2 to 4.3) in 2006 to 5.8% (95% CI = 5.7 to 5.9) in 2013 with a more pronounced trend after 2010 (P<0.0001). This increase was more significant for those who regularly consulted a GP. For these individuals, the policy led to a 20.4% increase (95% CI = 17.0 to 23.8) in HIV screening in 2013 compared with only a 4.5% increase (95% CI = 4.4 to 4.5) for those who did not consult a GP regularly in 2013. CONCLUSION: The results show that the mass screening policy coordinated by GPs had a significant impact on HIV testing in France, which could result in positive impacts on public and individual health outcomes. PMID- 27672142 TI - Nodular Skin Lesions in an Immunocompromised Patient. PMID- 27672143 TI - Nodular Skin Lesions in an Immunocompromised Patient. PMID- 27672141 TI - Access to, and experiences of, healthcare services by trafficked people: findings from a mixed-methods study in England. AB - BACKGROUND: Physical and psychological morbidity is high in trafficked people but little is known about their experiences of accessing and using healthcare services while, or after, being trafficked. AIM: To explore trafficked people's access to, and use of, health care during and after trafficking. DESIGN AND SETTING: A mixed-methods study - a cross-sectional survey comprising a structured interview schedule and open-ended questions - was undertaken in trafficked people's accommodation or support service offices across England. METHOD: Participants were asked open-ended questions regarding their use of healthcare services during and after trafficking. Interviews were conducted with professionally qualified interpreters where required. Thematic analysis was used to analyse the data. RESULTS: In total, 136 trafficked people (from 160 contacted) participated in the open-ended interviews of whom 91 (67%) were female and 45 (33%) male. Participants reported being trafficked for domestic servitude (n = 40; 29%), sexual exploitation (n = 41; 30%), and labour exploitation (for example, agriculture or factory work) (n = 52; 38%). Many responders reported that traffickers restricted access to services, accompanied them, or interpreted for them during consultations. Requirements to present identity documents to register for care, along with poor access to interpreters, were barriers to care during and after trafficking. Advocacy and assistance from support workers were critical to health service access for people who have been trafficked. CONCLUSION: Trafficked people access health services during and after the time they are exploited, but encounter significant barriers. GPs and other practitioners would benefit from guidance on how these people can be supported to access care, especially if they lack official documentation. PMID- 27672144 TI - Enhancing Literacy in Cardiovascular Genetics: A Scientific Statement From the American Heart Association. AB - Advances in genomics are enhancing our understanding of the genetic basis of cardiovascular diseases, both congenital and acquired, and stroke. These advances include finding genes that cause or increase the risk for childhood and adult onset diseases, finding genes that influence how patients respond to medications, and the development of genetics-guided therapies for diseases. However, the ability of cardiovascular and stroke clinicians to fully understand and apply this knowledge to the care of their patients has lagged. This statement addresses what the specialist caring for patients with cardiovascular diseases and stroke should know about genetics; how they can gain this knowledge; how they can keep up-to-date with advances in genetics, genomics, and pharmacogenetics; and how they can apply this knowledge to improve the care of patients and families with cardiovascular diseases and stroke. PMID- 27672145 TI - Single-molecule imaging of electroporated dye-labelled CheY in live Escherichia coli. AB - For the past two decades, the use of genetically fused fluorescent proteins (FPs) has greatly contributed to the study of chemotactic signalling in Escherichia coli including the activation of the response regulator protein CheY and its interaction with the flagellar motor. However, this approach suffers from a number of limitations, both biological and biophysical: for example, not all fusions are fully functional when fused to a bulky FP, which can have a similar molecular weight to its fused counterpart; they may interfere with the native interactions of the protein and the chromophores of FPs have low brightness and photostability and fast photobleaching rates. A recently developed technique for the electroporation of fluorescently labelled proteins in live bacteria has enabled us to bypass these limitations and study the in vivo behaviour of CheY at the single-molecule level. Here we show that purified CheY proteins labelled with organic dyes can be internalized into E. coli cells in controllable concentrations and imaged with video fluorescence microscopy. The use of this approach is illustrated by showing single CheY molecules diffusing within cells and interacting with the sensory clusters and the flagellar motors in real time.This article is part of the themed issue 'The new bacteriology'. PMID- 27672146 TI - Life: the first two billion years. AB - Microfossils, stromatolites, preserved lipids and biologically informative isotopic ratios provide a substantial record of bacterial diversity and biogeochemical cycles in Proterozoic (2500-541 Ma) oceans that can be interpreted, at least broadly, in terms of present-day organisms and metabolic processes. Archean (more than 2500 Ma) sedimentary rocks add at least a billion years to the recorded history of life, with sedimentological and biogeochemical evidence for life at 3500 Ma, and possibly earlier; phylogenetic and functional details, however, are limited. Geochemistry provides a major constraint on early evolution, indicating that the first bacteria were shaped by anoxic environments, with distinct patterns of major and micronutrient availability. Archean rocks appear to record the Earth's first iron age, with reduced Fe as the principal electron donor for photosynthesis, oxidized Fe the most abundant terminal electron acceptor for respiration, and Fe a key cofactor in proteins. With the permanent oxygenation of the atmosphere and surface ocean ca 2400 Ma, photic zone O2 limited the access of photosynthetic bacteria to electron donors other than water, while expanding the inventory of oxidants available for respiration and chemoautotrophy. Thus, halfway through Earth history, the microbial underpinnings of modern marine ecosystems began to take shape.This article is part of the themed issue 'The new bacteriology'. PMID- 27672147 TI - L-form bacteria, chronic diseases and the origins of life. AB - The peptidoglycan cell wall is widely conserved across the bacterial domain, suggesting that it appeared early in the evolution of bacteria. It is normally essential but under certain conditions wall-deficient or 'L-form' bacteria can be isolated. In Bacillus subtilis this normally requires two genetic changes. The first, exemplified by mutations shutting down wall precursor synthesis, works by increasing membrane synthesis. This promotes the unusual form of proliferation used by L-forms, involving a range of relatively disorganized membrane blebbing or vesiculation events. The secondary class of mutations probably work by relieving oxidative stress that L-forms may incur due to their unbalanced metabolism. Repression or inhibition of cell wall precursor synthesis can stimulate the L-form transition in a wide range of bacteria, of both Gram positive and -negative lineages. L-forms are completely resistant to most antibiotics working specifically on cell wall synthesis, such as penicillins and cephalosporins, consistent with the many reports of their involvement in various chronic diseases. They are potentially important in biotechnology, because lack of a wall can be advantageous in a range of production or strain improvement applications. Finally, L-forms provide an interesting model system for studying early steps in the evolution of cellular life.This article is part of the themed issue 'The new bacteriology'. PMID- 27672151 TI - From homeostasis to pathology: decrypting microbe-host symbiotic signals in the intestinal crypt. AB - Metagenomic analysis of the human intestinal microbiome has provided a wealth of information that allowed an exceptionally detailed description of its microbial content and physiological potential. It also set the basis for studies allowing correlation of alterations in the balance of this microbiota and the occurrence of a certain number of emerging diseases, such as inflammatory bowel diseases, obesity and diabetes, and possibly colorectal cancer. The time has come to give the intestinal microbiota in symbiosis with its host an experimental dimension. This brief review summarizes our attempt at developing a cellular microbiology of the mutualistic symbiosis established between the gut microbiota and the host intestinal surface. Particular attention is paid to the intestinal crypt, due to its role in epithelial regeneration.This article is part of the themed issue 'The new bacteriology'. PMID- 27672149 TI - Trigger phosphodiesterases as a novel class of c-di-GMP effector proteins. AB - The bacterial second messenger c-di-GMP controls bacterial biofilm formation, motility, cell cycle progression, development and virulence. It is synthesized by diguanylate cyclases (with GGDEF domains), degraded by specific phosphodiesterases (PDEs, with EAL of HD-GYP domains) and sensed by a wide variety of c-di-GMP-binding effectors that control diverse targets. c-di-GMP binding effectors can be riboswitches as well as proteins with highly diverse structures and functions. The latter include 'degenerate' GGDEF/EAL domain proteins that are enzymatically inactive but still able to bind c-di-GMP. Surprisingly, two enzymatically active 'trigger PDEs', the Escherichia coli proteins PdeR and PdeL, have recently been added to this list of c-di-GMP-sensing effectors. Mechanistically, trigger PDEs are multifunctional. They directly and specifically interact with a macromolecular target (e.g. with a transcription factor or directly with a promoter region), whose activity they control by their binding and degradation of c-di-GMP-their PDE activity thus represents the c-di GMP sensor or effector function. In this process, c-di-GMP serves as a regulatory ligand, but in contrast to classical allosteric control, this ligand is also degraded. The resulting kinetics and circuitry of control are ideally suited for trigger PDEs to serve as key components in regulatory switches.This article is part of the themed issue 'The new bacteriology'. PMID- 27672148 TI - CRISPR-Cas: biology, mechanisms and relevance. AB - Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes-termed spacers-into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent.This article is part of the themed issue 'The new bacteriology'. PMID- 27672150 TI - Shedding light on biology of bacterial cells. AB - To understand basic principles of living organisms one has to know many different properties of all cellular components, their mutual interactions but also their amounts and spatial organization. Live-cell imaging is one possible approach to obtain such data. To get multiple snapshots of a cellular process, the imaging approach has to be gentle enough to not disrupt basic functions of the cell but also have high temporal and spatial resolution to detect and describe the changes. Light microscopy has become a method of choice and since its early development over 300 years ago revolutionized our understanding of living organisms. As most cellular components are indistinguishable from the rest of the cellular contents, the second revolution came from a discovery of specific labelling techniques, such as fusions to fluorescent proteins that allowed specific tracking of a component of interest. Currently, several different tags can be tracked independently and this allows us to simultaneously monitor the dynamics of several cellular components and from the correlation of their dynamics to infer their respective functions. It is, therefore, not surprising that live-cell fluorescence microscopy significantly advanced our understanding of basic cellular processes. Current cameras are fast enough to detect changes with millisecond time resolution and are sensitive enough to detect even a few photons per pixel. Together with constant improvement of properties of fluorescent tags, it is now possible to track single molecules in living cells over an extended period of time with a great temporal resolution. The parallel development of new illumination and detection techniques allowed breaking the diffraction barrier and thus further pushed the resolution limit of light microscopy. In this review, we would like to cover recent advances in live-cell imaging technology relevant to bacterial cells and provide a few examples of research that has been possible due to imaging.This article is part of the themed issue 'The new bacteriology'. PMID- 27672152 TI - Old concepts, new molecules and current approaches applied to the bacterial nucleotide signalling field. AB - Signalling nucleotides are key molecules that help bacteria to rapidly coordinate cellular pathways and adapt to changes in their environment. During the past 10 years, the nucleotide signalling field has seen much excitement, as several new signalling nucleotides have been discovered in both eukaryotic and bacterial cells. The fields have since advanced quickly, aided by the development of important tools such as the synthesis of modified nucleotides, which, combined with sensitive mass spectrometry methods, allowed for the rapid identification of specific receptor proteins along with other novel genome-wide screening methods. In this review, we describe the principle concepts of nucleotide signalling networks and summarize the recent work that led to the discovery of the novel signalling nucleotides. We also highlight current approaches applied to the research in the field as well as resources and methodological advances aiding in a rapid identification of nucleotide-specific receptor proteins.This article is part of the themed issue 'The new bacteriology'. PMID- 27672153 TI - When pathogenic bacteria meet the intestinal microbiota. AB - The intestinal microbiota is a large and diverse microbial community that inhabits the intestinal tract, containing about 100 trillion bacteria from 500 1000 distinct species that, collectively, provide multiple benefits to the host. The gut microbiota contributes to nutrient absorption and maturation of the immune system, and also plays a central role in protection of the host from enteric bacterial infection. On the other hand, many enteric pathogens have developed strategies in order to be able to outcompete the intestinal community, leading to infection and/or chronic diseases. This review will summarize findings describing the complex relationship occurring between the intestinal microbiota and enteric pathogens, as well as how future therapies can ultimately benefit from such discoveries.This article is part of the themed issue 'The new bacteriology'. PMID- 27672156 TI - The new bacteriology. PMID- 27672154 TI - Convergent evolution of pathogenicity islands in helper cos phage interference. AB - Staphylococcus aureus pathogenicity islands (SaPIs) are phage satellites that exploit the life cycle of their helper phages for their own benefit. Most SaPIs are packaged by their helper phages using a headful (pac) packaging mechanism. These SaPIs interfere with pac phage reproduction through a variety of strategies, including the redirection of phage capsid assembly to form small capsids, a process that depends on the expression of the SaPI-encoded cpmA and cpmB genes. Another SaPI subfamily is induced and packaged by cos-type phages, and although these cos SaPIs also block the life cycle of their inducing phages, the basis for this mechanism of interference remains to be deciphered. Here we have identified and characterized one mechanism by which the SaPIs interfere with cos phage reproduction. This mechanism depends on a SaPI-encoded gene, ccm, which encodes a protein involved in the production of small isometric capsids, compared with the prolate helper phage capsids. As the Ccm and CpmAB proteins are completely unrelated in sequence, this strategy represents a fascinating example of convergent evolution. Moreover, this result also indicates that the production of SaPI-sized particles is a widespread strategy of phage interference conserved during SaPI evolution.This article is part of the themed issue 'The new bacteriology'. PMID- 27672155 TI - Inhibiting Mycobacterium tuberculosis within and without. AB - Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials. Attempts to find new lead compounds employing target-based screens were unsuccessful as the leads were inactive against M. tuberculosis Greater success was achieved using phenotypic screening against live tubercle bacilli and this gave rise to the drugs bedaquiline, pretomanid and delamanid, currently in phase III trials. Subsequent phenotypic screens also uncovered new leads and targets but several of these targets proved to be promiscuous and inhibited by a variety of seemingly unrelated pharmacophores. This setback sparked an interest in alternative screening approaches that mimic the disease state more accurately. Foremost among these were cell-based screens, often involving macrophages, as these should reflect the bacterium's niche in the host more faithfully. A major advantage of this approach is its ability to uncover functions that are central to infection but not necessarily required for growth in vitro For instance, inhibition of virulence functions mediated by the ESX-1 secretion system severely attenuates intracellular M. tuberculosis, preventing intercellular spread and ultimately limiting tissue damage. Cell-based screens have highlighted the druggability of energy production via the electron transport chain and cholesterol metabolism. Here, I review the scientific progress and the pipeline, but warn against over optimism due to the lack of industrial commitment for tuberculosis drug development and other socio-economic factors.This article is part of the themed issue 'The new bacteriology'. PMID- 27672157 TI - RNA polymerase supply and flux through the lac operon in Escherichia coli. AB - Chromatin immunoprecipitation, followed by quantification of immunoprecipitated DNA, can be used to measure RNA polymerase binding to any DNA segment in Escherichia coli By calibrating measurements against the signal from a single RNA polymerase bound at a single promoter, we can calculate both promoter occupancy levels and the flux of transcribing RNA polymerase through transcription units. Here, we have applied the methodology to the E. coli lactose operon promoter. We confirm that promoter occupancy is limited by recruitment and that the supply of RNA polymerase to the lactose operon promoter depends on its location in the E. coli chromosome. Measurements of RNA polymerase binding to DNA segments within the lactose operon show that flux of RNA polymerase through the operon is low, with, on average, over 18 s elapsing between the passage of transcribing polymerases. Similar low levels of flux were found when semi-synthetic promoters were used to drive transcript initiation, even when the promoter elements were changed to ensure full occupancy of the promoter by RNA polymerase.This article is part of the themed issue 'The new bacteriology'. PMID- 27672158 TI - Molecular phenotyping of infection-associated small non-coding RNAs. AB - Infection is a complicated balance, with both pathogen and host struggling to tilt the result in their favour. Bacterial infection biology has relied on forward genetics for many of its advances, defining phenotype in terms of replication in model systems. However, many known virulence factors fail to produce robust phenotypes, particularly in the systems most amenable to genetic manipulation, such as cell-culture models. This has particularly been limiting for the study of the bacterial regulatory small RNAs (sRNAs) in infection. We argue that new sequencing-based technologies can work around this problem by providing a 'molecular phenotype', defined in terms of the specific transcriptional dysregulation in the infection system induced by gene deletion. We illustrate this using the example of our recent study of the PinT sRNA using dual RNA-seq, that is, simultaneous RNA sequencing of host and pathogen during infection. We additionally discuss how other high-throughput technologies, in particular genetic interaction mapping using transposon insertion sequencing, may be used to further dissect molecular phenotypes. We propose a strategy for how high-throughput technologies can be integrated in the study of non-coding regulators as well as bacterial virulence factors, enhancing our ability to rapidly generate hypotheses with regards to their function.This article is part of the themed issue 'The new bacteriology'. PMID- 27672160 TI - Correction to 'Increasing western US forest wildfire activity: sensitivity to changes in the timing of spring'. PMID- 27672159 TI - Hypothesis: type I toxin-antitoxin genes enter the persistence field-a feedback mechanism explaining membrane homoeostasis. AB - Bacteria form persisters, cells that are tolerant to multiple antibiotics and other types of environmental stress. Persister formation can be induced either stochastically in single cells of a growing bacterial ensemble, or by environmental stresses, such as nutrient starvation, in a subpopulation of cells. In many cases, the molecular mechanisms underlying persistence are still unknown. However, there is growing evidence that, in enterobacteria, both stochastically and environmentally induced persistence are controlled by the second messenger (p)ppGpp. For example, the 'alarmone' (p)ppGpp activates Lon, which, in turn, activates type II toxin-antitoxin (TA) modules to thereby induce persistence. Recently, it has been shown that a type I TA module, hokB/sokB, also can induce persistence. In this case, the underlying mechanism depends on the universally conserved GTPase Obg and, surprisingly, also (p)ppGpp. In the presence of (p)ppGpp, Obg stimulates hokB transcription and induces persistence. HokB toxin expression is under both negative and positive control: SokB antisense RNA inhibits hokB mRNA translation, while (p)ppGpp and Obg together stimulate hokB transcription. HokB is a small toxic membrane protein that, when produced in modest amounts, leads to membrane depolarization, cell stasis and persistence. By contrast, overexpression of HokB disrupts the membrane potential and kills the cell. These observations raise the question of how expression of HokB is regulated. Here, I propose a homoeostatic control mechanism that couples HokB expression to the membrane-bound RNase E that degrades and inactivates SokB antisense RNA.This article is part of the themed issue 'The new bacteriology'. PMID- 27672164 TI - Linking Inflammation and Parkinson Disease: Hypochlorous Acid Generates Parkinsonian Poisons. PMID- 27672161 TI - Is High Blood Pressure Self-Protection for the Brain? AB - RATIONALE: Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular variants of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the pathogenesis of essential hypertension, which remains enigmatic in 95% of patients. OBJECTIVE: To evaluate the role of the cerebral circulation in the pathophysiology of hypertension. METHODS AND RESULTS: We completed a series of retrospective and mechanistic case-control magnetic resonance imaging and physiological studies in normotensive and hypertensive humans (n=259). Interestingly, in humans with hypertension, we report a higher prevalence of congenital cerebrovascular variants; vertebral artery hypoplasia, and an incomplete posterior circle of Willis, which were coupled with increased cerebral vascular resistance, reduced cerebral blood flow, and a higher incidence of lacunar type infarcts. Causally, cerebral vascular resistance was elevated before the onset of hypertension and elevated sympathetic nerve activity (n=126). Interestingly, untreated hypertensive patients (n=20) had a cerebral blood flow similar to age-matched controls (n=28). However, participants receiving antihypertensive therapy (with blood pressure controlled below target levels) had reduced cerebral perfusion (n=19). Finally, elevated cerebral vascular resistance was a predictor of hypertension, suggesting that it may be a novel prognostic or diagnostic marker (n=126). CONCLUSIONS: Our data indicate that congenital cerebrovascular variants in the posterior circulation and the associated cerebral hypoperfusion may be a factor in triggering hypertension. Therefore, lowering blood pressure may worsen cerebral perfusion in susceptible individuals. PMID- 27672165 TI - The terrorist inside my husband's brain. PMID- 27672163 TI - Mechanisms of Action Point Towards Combined PBDE/NDL-PCB Risk Assessment. AB - At present, human risk assessment of the structurally similar non-dioxin-like (NDL) PCBs and polybrominated diphenylethers (PBDEs) is done independently for both groups of compounds. There are however obvious similarities between NDL-PCBs and PBDEs with regard to modulation of the intracellular calcium homeostasis (basal calcium levels, voltage-gated calcium channels, calcium uptake, ryanodine receptor) and thyroid hormone (TH) homeostasis (TH levels and transport). which are mechanisms of action related to neurobehavioral effects (spontaneous activity, habituation and learning ability). There also similarities in agonistic interactions with the hepatic nuclear receptors PXR and CAR. Several effects on developmental (reproductive) processes have also been observed, but results were more dispersed and insufficient to compare both groups of compounds. The available mechanistic information is sufficient to warrant a dose addition model for NDL-PCBs and PBDEs, including their hydroxylated metabolites.Although many of the observed effects are similar from a qualitative point of view for both groups, congener or tissue specific differences have also been found. As this is a source of uncertainty in the combined hazard and risk assessment of these compounds, molecular entities involved in the observed mechanisms and adverse outcomes associated with these compounds need to be identified. The systematical generation of (quantitative) structure-activity information for NDL-PCBs and PBDEs on these targets (including potential non-additive effects) will allow a more realistic risk estimation associated with combined exposure to both groups of compounds during early life. Additional validation studies are needed to quantify these uncertainties for risk assessment of NDL-PCBs and PBDEs. PMID- 27672166 TI - A rare case of extensive primary meningeal osteosarcoma in childhood. PMID- 27672167 TI - A case of sudden deterioration in Parkinson disease. PMID- 27672168 TI - Pearls & Oy-sters: Tacrolimus neurotoxicity presenting as an isolated brainstem lesion. PMID- 27672169 TI - Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. PMID- 27672170 TI - Mystery Case: Terson syndrome on CT head. PMID- 27672171 TI - Clinical Reasoning: An 87-year-old man with chronic obstructive pulmonary disease and acute encephalopathy. PMID- 27672173 TI - Teaching NeuroImages: Acquired hepatocerebral degeneration: An underrecognized complication of advanced liver disease. PMID- 27672172 TI - Clinical Reasoning: A 52-year-old man with diplopia and ataxia. PMID- 27672174 TI - Telestroke: Is it safe and effective? PMID- 27672176 TI - Neural substrates of the ability to recognize facial expressions: a voxel-based morphometry study. AB - The recognition of facial expressions of emotion is adaptive for human social interaction, but the ability to do this and the manner in which it is achieved differs among individuals. Previous functional neuroimaging studies have demonstrated that some brain regions, such as the inferior frontal gyrus (IFG), are active during the response to emotional facial expressions in healthy participants, and lesion studies have demonstrated that damage to these structures impairs the recognition of facial expressions. However, it remains to be established whether individual differences in the structure of these regions could be associated with differences in the ability to recognize facial expressions. We investigated this issue using acquired structural magnetic resonance imaging, and assessed the performance of healthy adults with respect to recognition of the facial expressions of six basic emotions. The gray matter volume of the right IFG positively correlated with the total accuracy of facial expression recognition. This suggests that individual differences in the ability to recognize facial expressions are associated with differences in the structure of the right IFG. Furthermore, the mirror neuron activity of the IFG may be important for establishing efficient facial mimicry to facilitate emotion recognition. PMID- 27672177 TI - Refusal of HIV testing among black Africans attending sexual health clinics in England, 2014: a review of surveillance data. AB - OBJECTIVES: Black Africans are one of the key risk groups for HIV in the UK and, among those living with HIV, an estimated 16% and 12% of black African heterosexual men and women, respectively, are undiagnosed and at risk of unknowingly transmitting HIV to their sex partners. Increased HIV test uptake is needed to address this, but there is limited information on how frequently HIV test refusal occurs among those attending sexual health clinics (SHCs). We identified factors associated with HIV test refusal among black African SHC attendees. METHODS: Data on all SHC attendances in England in 2014 were obtained from the genitourinary medicine clinic activity dataset, the mandatory surveillance system for STIs. Analyses were restricted to attendances by HIV negative black Africans, and bivariate and multivariable associations between demographic and clinical characteristics and HIV test refusal were assessed. All associations were determined using generalised estimating equations logistic regression, and adjusted ORs (aORs) with 95% CIs are reported. RESULTS: Black Africans made 80 743 attendances at SHCs in 2014 and refused an HIV test on 9021 (11.2%) occasions. HIV test refusal was significantly more likely in women (aOR (95% CI) 1.54 (1.46 to 1.62) vs heterosexual men), and those living in the most deprived areas (1.44 (1.24 to 1.67)), diagnosed with a new STI (1.26 (1.18 to 1.34)) or living in London (1.06 (1.01 to 1.12)). Test refusal was significantly less likely with increasing age (0.99 (0.99 to 0.99)) and men who have sex with men (0.52 (0.43 to 0.63) vs heterosexual men), and in those tested for HIV in the past year (0.85 (0.81 to 0.89)), born outside the UK (0.73 (0.69 to 0.77)) or those attending following partner notification (0.11 (0.03 to 0.38)). CONCLUSIONS: Targeted interventions are needed to improve HIV testing uptake and reduce undiagnosed HIV infection among black Africans attending SHCs, especially heterosexuals residing in deprived areas. PMID- 27672178 TI - eComment. Phosphocreatine in cardiovascular disease: how can we relate the evidence to clinical practice? PMID- 27672175 TI - Grit and the brain: spontaneous activity of the dorsomedial prefrontal cortex mediates the relationship between the trait grit and academic performance. AB - As a personality trait, grit involves the tendency to strive to achieve long-term goals with continual passion and perseverance and plays an extremely crucial role in personal achievement. However, the neural mechanisms of grit remain largely unknown. In this study, we aimed to explore the association between grit and the fractional amplitude of low-frequency fluctuations (fALFF) in 217 healthy adolescent students using resting-state functional magnetic resonance imaging (RS fMRI). We found that an individual's grit was negatively related to the regional fALFF in the right dorsomedial prefrontal cortex (DMPFC), which is involved in self-regulation, planning, goal setting and maintenance, and counterfactual thinking for reflecting on past failures. The results persisted even after the effects of general intelligence and the 'big five' personality traits were adjusted for. More importantly, the fALFF of the right DMPFC played a mediating role in the association between grit and academic performance. Overall, these findings reveal regional fALFF as a neural basis of grit and highlight the right DMPFC as a neural link between grit and academic performance. PMID- 27672179 TI - eReply. Phosphocreatine in cardiovascular disease: how can we relate the evidence to clinical practice? PMID- 27672181 TI - Contribution of occupational factors to the incidence and persistence of chronic low back pain among workers: results from the longitudinal VISAT study. AB - OBJECTIVE: Among the aetiological factors of chronic low back pain (CLBP), occupational factors are often suspected, but their contribution remains to be ascertained. This study aimed to determine the impact of a wide range of occupational factors on the incidence and persistence of CLBP. METHOD: From the VISAT (VIeillissement SAnte Travail) study, 1560 workers were examined at baseline and 5 years later. CLBP was defined as having low back pain or specific treatment for at least 6 months. Participants newly affected with CLBP and those with persistent CLBP at follow-up were distinguished. In addition to individual factors, a broad panel of occupational factors were analysed, covering employment, physical, organisational and psychosocial factors. Multivariate analyses were used to determine predictive factors of incidence and persistence of CLBP. Receiver operating characteristic (ROC) curves were performed to analyse the contribution of occupational factors. RESULTS: 22.6% of participants without any CLBP initially presented with CLBP 5 years later, while 53.7% of participants with CLBP at baseline had CLBP at the second collection. Carrying heavy loads, the lack of recognition of completed work and productivity-related income predicted a higher risk of incidence of CLBP. However, no significant association between occupational factors and the risk for persistence of CLBP was observed, while the risk was multiplied by two for history of depression and rheumatological events. ROC curves confirmed the significant contribution of occupational factors to incidence of CLBP. CONCLUSIONS: Occupational factors played a pivotal role in the incidence of CLBP, while individual factors were the main determinants of persistence of CLBP. PMID- 27672183 TI - Dynamical properties and thresholds of an HIV model with super-infection. AB - Super-infection by multiple HIV-1 subtypes, previously thought restricted to high risk groups, has now been reported in the general heterosexual populations at relatively the same incidence rate as in high risk groups. We present a simple deterministic HIV model with super-infection by two HIV-1 subtypes. Mathematical characteristics including the basic reproductive number $(?mathcal{R}_0)$, invasion threshold $(?mathcal{R}_{21},?mathcal{R}_{12})$ and conditions for asymptotic stability are derived. In the absence of super-infection the model exhibits competitive exclusion, and all equilibria are globally attracting if they exist except for the disease free which is a saddle for $?mathcal{R}_0>1.$ The results show that the subtype with the dominant reproductive number exceeding unity dominates the weaker subtype forcing it to extinction regardless of the size of the reproductive number. On the other end, super-infection may promote subtype co-existence whenever the minimum of the subtype specific reproductive numbers $(?mathcal{R}_1,?mathcal{R}_2)$ and the invasion reproductive numbers $(?mathcal{R}_{12},?mathcal{R}_{21})$ exceed unity. Our results demonstrate that if the partial reproductive numbers $(?mathcal{R}_1~?mbox{and}~?mathcal{R}_2 )$ and the invasion reproductive number for the weaker subtype $(?mathcal{R}_{21})$ satisfy $?mathcal{R}_2<1,~?mathcal{R}_1>1~?mbox{and}~?mathcal{R}_{21}>1,$ then primary infection by subtype $1$ may stay the extinction of subtype $2$ despite its relatively low reproductive fitness. For certain parameter ranges, hysteresis (including backward bifurcation) occurs with possible differences in the asymptotic level of disease prevalence. Super-infection may thus facilitate the continued re-generation of reproductively noncompetent subtypes whose subtype specific reproductive numbers will be less than unity while at the same time allowing for the mutual coexistence and persistence of multiple strains. Persistence and co-existence of multiple strains has detrimental effect on vaccine design and development and administration of ART where one or more of the strains are drug resistant. PMID- 27672182 TI - Multiscale simulation of thrombus growth and vessel occlusion triggered by collagen/tissue factor using a data-driven model of combinatorial platelet signalling. AB - During clotting under flow, platelets bind and activate on collagen and release autocrinic factors such as ADP and thromboxane, while tissue factor (TF) on the damaged wall leads to localized thrombin generation. Towards patient-specific simulation of thrombosis, a multiscale approach was developed to account for: platelet signalling [neural network (NN) trained by pairwise agonist scanning (PAS), PAS-NN], platelet positions (lattice kinetic Monte Carlo, LKMC), wall generated thrombin and platelet-released ADP/thromboxane convection-diffusion (partial differential equation, PDE) and flow over a growing clot (lattice Boltzmann). LKMC included shear-driven platelet aggregate restructuring. The PDEs for thrombin, ADP and thromboxane were solved by finite element method using cell activation-driven adaptive triangular meshing. At all times, intracellular calcium was known for each platelet by PAS-NN in response to its unique exposure to local collagen, ADP, thromboxane and thrombin. When compared with microfluidic experiments of human blood clotting on collagen/TF driven by constant pressure drop, the model accurately predicted clot morphology and growth with time. In experiments and simulations at TF at 0.1 and 10 molecule-TF/$?mu$m$^{2}$ and initial wall shear rate of 200 s$^{-1}$, the occlusive blockade of flow for a 60 $?mu$m channel occurred relatively abruptly at 600 and 400 s, respectively (with no occlusion at zero TF). Prior to occlusion, intrathrombus concentrations reached 50 nM thrombin, ~ 1 $?mu$M thromboxane and ~ 10 $?mu$M ADP, while the wall shear rate on the rough clot peaked at ~ 1000-2000 s$^{-1}$. Additionally, clotting on TF/collagen was accurately simulated for modulators of platelet cyclooxygenase-1, P2Y$_{1}$ and IP-receptor. This multiscale approach facilitates patient-specific simulation of thrombosis under hemodynamic and pharmacological conditions. PMID- 27672187 TI - The acclimation of Tilia cordata stomatal opening in response to light, and stomatal anatomy to vegetational shade and its components. AB - Stomatal anatomical traits and rapid responses to several components of visible light were measured in Tilia cordata Mill. seedlings grown in an open, fully sunlit field (C-set), or under different kinds of shade. The main questions were: (i) stomatal responses to which visible light spectrum regions are modified by growth-environment shade and (ii) which separate component of vegetational shade is most effective in eliciting the acclimation effects of the full vegetational shade. We found that stomatal opening in response to red or green light did not differ between the plants grown in the different environments. Stomatal response to blue light was increased (in comparison with that of C-set) in the leaves grown in full vegetational shade (IABW-set), in attenuated UVAB irradiance (AB set) or in decreased light intensity (neutral shade) plus attenuated UVAB irradiance (IAB-set). In all sets, the addition of green light-two or four times stronger-into induction light barely changed the rate of the blue-light stimulated stomatal opening. In the AB-set, stomatal response to blue light equalled the strong IABW-set response. In attenuated UVB-grown leaves, stomatal response fell midway between IABW- and C-set results. Blue light response by neutral shade-grown leaves did not differ from that of the C-set, and the response by the IAB-set did not differ from that of the AB-set. Stomatal size was not modified by growth environments. Stomatal density and index were remarkably decreased only in the IABW- and IAB-sets. It was concluded that differences in white light responses between T. cordata leaves grown in different light environments are caused only by their different blue light response. Differences in stomatal sensitivity are not dependent on altered stomatal anatomy. Attenuated UVAB irradiance is the most efficient component of vegetational shade in stimulating acclimation of stomata, whereas decreased light intensity plays a minor role. PMID- 27672189 TI - Trade-offs between water transport capacity and drought resistance in neotropical canopy liana and tree species. AB - In tropical forest canopies, it is critical for upper shoots to efficiently provide water to leaves for physiological function while safely preventing loss of hydraulic conductivity due to cavitation during periods of soil water deficit or high evaporative demand. We compared hydraulic physiology of upper canopy trees and lianas in a seasonally dry tropical forest to test whether trade-offs between safety and efficiency of water transport shape differences in hydraulic function between these two major tropical woody growth forms. We found that lianas showed greater maximum stem-specific hydraulic conductivity than trees, but lost hydraulic conductivity at less negative water potentials than trees, resulting in a negative correlation and trade-off between safety and efficiency of water transport. Lianas also exhibited greater diurnal changes in leaf water potential than trees. The magnitude of diurnal water potential change was negatively correlated with sapwood capacitance, indicating that lianas are highly reliant on conducting capability to maintain leaf water status, whereas trees relied more on stored water in stems to maintain leaf water status. Leaf nitrogen concentration was related to maximum leaf-specific hydraulic conductivity only for lianas suggesting that greater water transport capacity is more tied to leaf processes in lianas compared to trees. Our results are consistent with a trade off between safety and efficiency of water transport and may have implications for increasing liana abundance in neotropical forests. PMID- 27672190 TI - Towards more accurate vegetation mortality predictions. PMID- 27672191 TI - Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria. AB - : Mycobacteriophage DS6A is unique among the more than 8,000 isolated mycobacteriophages due to its ability to form plaques exclusively on mycobacteria belonging to the Mycobacterium tuberculosis complex (MTBC). Speculation surrounding this specificity has led to unsupported assertions in published studies and patents that nontuberculous mycobacteria (NTM) are wholly resistant to DS6A infection. In this study, we identified two independent nonessential regions in the DS6A genome and replaced them with an mVenus-expressing plasmid to generate fluorescent reporter phages Phi2GFP12 and Phi2GFP13. We show that even though DS6A is able to form plaques only on MTBC bacteria, infection of various NTM results in mVenus expression in transduced cells. The efficiency of DS6A in delivering DNA varied between NTM species. Additionally, we saw a striking difference in the efficiency of DNA delivery between the closely related members of the Mycobacterium abscessus complex, M. abscessus and Mycobacterium massiliense We also demonstrated that TM4 and DS6A, two phages that do not form plaques on M. massiliense, differ in their ability to deliver DNA, suggesting that there is a phage-specific restriction between mycobacterial species. Phylogenetic analysis reveals that the DS6A genome has a characteristically mosaic structure but provided few insights into the basis for the specificity for MTBC hosts. This study demonstrates that the inability of the MTBC-specific phage DS6A to form plaques on NTM is more complex than previously thought. Moreover, the DS6A-derived fluorophages provide important new tools for the study of mycobacterial biology. IMPORTANCE: The coevolution of bacteria and their infecting phages involves a constant arms race for bacteria to prevent phage infection and phage to overcome these preventions. Although a diverse array of phage defense systems is well characterized in bacteria, very few phage restriction systems are known in mycobacteria. The DS6A mycobacteriophage is unique in the mycobacterial world in that it forms plaques only on members of the Mycobacterium tuberculosis complex. However, the novel DS6A reporter phages developed in this work demonstrate that DS6A can infect nontuberculous mycobacteria at various efficiencies. By comparing the abilities of DS6A and another phage, TM4, to infect and form plaques on various mycobacterial species, we can begin to discern new phage restriction systems employed within the genus. PMID- 27672192 TI - Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes. AB - The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B2), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8 demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8 aminoriboflavin adenine dinucleotide (AFAD). In vivo reporter gene assays and in vitro transcription/translation experiments show that the L. monocytogenes FMN riboswitch Rli96, which controls expression of the riboflavin transport gene lmo1945, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of L. monocytogenes with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in L. monocytogenes IMPORTANCE: The riboflavin analogs roseoflavin (RoF) and 8 demethyl-8-aminoriboflavin (AF) are small molecules which are produced by Streptomyces davawensis and Streptomyces cinnabarinus RoF and AF were reported to have antibacterial activity, and we studied how these compounds are metabolized by the human bacterial pathogen Listeria monocytogenes We found that the L. monocytogenes protein Lmo1945 mediates uptake of AF and RoF and that the combined activities of the enzymes Lmo1329 and Lmo0728 are responsible for the conversion of AF and RoF to toxic cofactor analogs. Comparative studies with RoF and AF (a weaker antibiotic) suggest that the reduction in FMN/FAD levels and the formation of inactive FMN/FAD analogs explain to a large extent the antibiotic activity of AF and RoF. PMID- 27672193 TI - Implementation and Data Analysis of Tn-seq, Whole-Genome Resequencing, and Single Molecule Real-Time Sequencing for Bacterial Genetics. AB - Few discoveries have been more transformative to the biological sciences than the development of DNA sequencing technologies. The rapid advancement of sequencing and bioinformatics tools has revolutionized bacterial genetics, deepening our understanding of model and clinically relevant organisms. Although application of newer sequencing technologies to studies in bacterial genetics is increasing, the implementation of DNA sequencing technologies and development of the bioinformatics tools required for analyzing the large data sets generated remain a challenge for many. In this minireview, we have chosen to summarize three sequencing approaches that are particularly useful for bacterial genetics. We provide resources for scientists new to and interested in their application. Here, we discuss the analysis of data from transposon mutagenesis followed by deep sequencing (Tn-seq) to determine gene disruptions differentially represented in a mutant population and Illumina sequencing for identification of suppressor or other mutations, and we summarize single-molecule real-time (SMRT) sequencing for de novo genome assembly and the use of the output data for detection of DNA base modifications. PMID- 27672194 TI - The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival. AB - : The Lmb protein of Streptococcus agalactiae is described as an adhesin that binds laminin, a component of the human extracellular matrix. In this study, we revealed a new role for this protein in zinc uptake. We also identified two Lmb homologs, AdcA and AdcAII, redundant binding proteins that combine with the AdcCB translocon to form a zinc-ABC transporter. Expression of this transporter is controlled by the zinc concentration in the medium through the zinc-dependent regulator AdcR. Triple deletion of lmb, adcA, and adcAII, or that of the adcCB genes, impaired growth and cell separation in a zinc-restricted environment. Moreover, we found that this Adc zinc-ABC transporter promotes S. agalactiae growth and survival in some human biological fluids, suggesting that it contributes to the infection process. These results indicated that zinc has biologically vital functions in S. agalactiae and that, under the conditions tested, the Adc/Lmb transporter constitutes the main zinc acquisition system of the bacterium. IMPORTANCE: A zinc transporter, composed of three redundant binding proteins (Lmb, AdcA, and AdcAII), was characterized in Streptococcus agalactiae This system was shown to be essential for bacterial growth and morphology in zinc-restricted environments, including human biological fluids. PMID- 27672195 TI - The Self-Identity Protein IdsD Is Communicated between Cells in Swarming Proteus mirabilis Colonies. AB - : Proteus mirabilis is a social bacterium that is capable of self (kin) versus nonself recognition. Swarming colonies of this bacterium expand outward on surfaces to centimeter-scale distances due to the collective motility of individual cells. Colonies of genetically distinct populations remain separate, while those of identical populations merge. Ids proteins are essential for this recognition behavior. Two of these proteins, IdsD and IdsE, encode identity information for each strain. These two proteins bind in vitro in an allele restrictive manner. IdsD-IdsE binding is correlated with the merging of populations, whereas a lack of binding is correlated with the separation of populations. Key questions remained about the in vivo interactions of IdsD and IdsE, specifically, whether IdsD and IdsE bind within single cells or whether IdsD-IdsE interactions occur across neighboring cells and, if so, which of the two proteins is exchanged. Here we demonstrate that IdsD must originate from another cell to communicate identity and that this nonresident IdsD interacts with IdsE resident in the recipient cell. Furthermore, we show that unbound IdsD in recipient cells does not cause cell death and instead appears to contribute to a restriction in the expansion radius of the swarming colony. We conclude that P. mirabilis communicates IdsD between neighboring cells for nonlethal kin recognition, which suggests that the Ids proteins constitute a type of cell-cell communication. IMPORTANCE: We demonstrate that self (kin) versus nonself recognition in P. mirabilis entails the cell-cell communication of an identity encoding protein that is exported from one cell and received by another. We further show that this intercellular exchange affects swarm colony expansion in a nonlethal manner, which adds social communication to the list of potential swarm related regulatory factors. PMID- 27672197 TI - Superficial Femoral Artery Is Not Left Anterior Descending Artery. PMID- 27672196 TI - Structural Determinants for Antitoxin Identity and Insulation of Cross Talk between Homologous Toxin-Antitoxin Systems. AB - : Toxin-antitoxin (TA) systems are ubiquitous in bacteria and archaea, where they play a pivotal role in the establishment and maintenance of dormancy. Under normal growth conditions, the antitoxin neutralizes the toxin. However, under conditions of stress, such as nutrient starvation or antibiotic treatment, cellular proteases degrade the antitoxin, and the toxin functions to arrest bacterial growth. We characterized the specificity determinants of the interactions between VapB antitoxins and VapC toxins from nontypeable Haemophilus influenzae (NTHi) in an effort to gain a better understanding of how antitoxins control toxin activity and bacterial persistence. We studied truncated and full length antitoxins with single amino acid mutations in the toxin-binding domain. Coexpressing the toxin and antitoxin in Escherichia coli and measuring bacterial growth by dilution plating assayed the ability of the mutant antitoxins to neutralize the toxin. Our results identified two single amino acid residues (W48 and F52) in the C-terminal region of the VapB2 antitoxin necessary for its ability to neutralize its cognate VapC2 toxin. Additionally, we attempted to alter the specificity of VapB1 by making a mutation that would allow it to neutralize its noncognate toxin. A mutation in VapB1 to contain the tryptophan residue identified herein as important in the VapB2-VapC2 interaction resulted in a VapB1 mutant (the T47W mutant) that binds to and neutralizes both its cognate VapC1 and noncognate VapC2 toxins. This represents the first example of a single mutation causing relaxed specificity in a type II antitoxin. IMPORTANCE: Toxin antitoxin systems are of particular concern in pathogenic organisms, such as nontypeable Haemophilus influenzae, as they can elicit dormancy and persistence, leading to chronic infections and failure of antibiotic treatment. Despite the importance of the TA interaction, the specificity determinants for VapB-VapC complex formation remain uncharacterized. Thus, our understanding of how antitoxins control toxin-induced dormancy and bacterial persistence requires thorough investigation of antitoxin specificity for its cognate toxin. This study characterizes the crucial residues of the VapB2 antitoxin from NTHi necessary for its interaction with VapC2 and provides the first example of a single amino acid change altering the toxin specificity of an antitoxin. PMID- 27672199 TI - Long-Term Follow-Up of the Randomized (BIOMArCS-2) Glucose Trial: Intensive Glucose Regulation in Hyperglycemic Acute Coronary Syndrome. PMID- 27672200 TI - Letter by Koh Regarding Article, "Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: 16 Years of Follow-Up of the LIPID Study". PMID- 27672201 TI - Letter by Melgari et al Regarding Article, "Ivabradine: Role in the Chronic Heart Failure Armamentarium". PMID- 27672202 TI - Correction to: 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. PMID- 27672203 TI - P2X7R Gene Polymorphisms are Associated with Increased Risk of Pulmonary Tuberculosis in the Tibetan Chinese Population. AB - In this study, we aim to explore the correlation between single nucleotide polymorphisms (SNPs) in the P2X7R gene and pulmonary tuberculosis (PTB) susceptibility in the Tibetan Chinese population in China. We examined 467 patients with active PTB and 504 healthy controls living in Xi'an and the surrounding area. Eight P2X7R SNPs were genotyped, and association analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were tested by unconditional logistic regression analysis to evaluate the effects of the polymorphisms on PTB risk. P2X7R SNP association analyses were performed using SPSS 17.0 statistical packages and Microsoft Excel, SNP statistics software, Haploview software package (version 4.2), and SHEsis software platform. The results show that the "C" allele of rs656612 in the P2X7R gene was associated with an increased PTB risk by the additive model (OR = 1.307, 95% CI = 1.088 1.570, P = 0.004) and dominant model (rs656612, OR = 1.490, 95% CI = 1.153-1.926, P = 0.002). The "A" allele of rs208290 showed an increased PTB risk by the additive model (OR = 1.418, 95% CI = 1.179-1.706, P < 0.001) and dominant model (OR = 1.680, 95% CI = 1.297-2.177, P < 0.001), whereas the "A" allele of rs7958311 showed an increased risk by the additive model (rs7958311, OR = 1.260, 95% CI = 1.055-1.505, P = 0.011) and recessive model (OR = 1.609, 95% CI = 1.200 2.158, P = 0.001). After Bonferroni correction, rs208290 was found to be associated with PTB in the allele, dominant, and genotype models. In conclusion, our study revealed a significant association between three P2X7R gene polymorphisms (rs656612, rs208290, and rs7958311) and PTB in a Tibetan Chinese population. PMID- 27672205 TI - Malarial Infection and Curable Sexually Transmitted and Reproductive Tract Infections Among Pregnant Women in a Rural District of Zambia. AB - Malarial infection and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes. Reducing the burden of these infections in pregnancy requires interventions that can be easily integrated into the antenatal care (ANC) package. However, efforts to integrate the control of malarial infection and curable STIs/RTIs in pregnancy have been hampered by a lack of evidence related to their coinfection. Thus, we investigated the prevalence of coinfection among pregnant women of rural Zambia. A prospective cohort study was conducted in Nchelenge District, Zambia, involving 1,086 first ANC attendees. We screened participants for peripheral malarial infection and curable STIs/RTIs (syphilis, Chlamydia, gonorrhea, trichomoniasis, and bacterial vaginosis), and collected relevant sociodemographic data at booking. Factors associated with malarial and STI/RTI coinfection were explored using univariate and multivariate regression models. Among participants with complete results (N = 1,071), 38.7% (95% confidence interval [CI] = 35.7-41.6) were coinfected with malaria parasites and at least one STI/RTI; 18.9% (95% CI = 16.5-21.2) were infected with malaria parasites only; 26.0% (95% CI = 23.5-28.8) were infected with at least one STI/RTI but no malaria parasites, and 16.4% (95% CI = 14.1-18.6) had no infection. Human immunodeficiency virus (HIV)-infected women had a higher risk of being coinfected than HIV-uninfected women (odds ratio [OR] = 3.59 [95% CI = 1.73-7.48], P < 0.001). The prevalence of malarial and STI/RTI coinfection was high in this population. An integrated approach to control malarial infection and STIs/RTIs is needed to reduce this dual burden in pregnancy. PMID- 27672204 TI - West Nile Virus Infection in Human and Mouse Cornea Tissue. AB - The purpose of this study was to determine the in vitro and ex vivo susceptibility of human corneal cells to West Nile virus (WNV) infection and evaluate the ability of the virus to disseminate to the corneas of infected mice. Human corneal epithelial cells were challenged with WNV, incubated for 1-6 days, and tested for evidence of WNV infection. Viral RNA and antigen were detected at every time point, and the virus reached a peak titer of 2.5 * 107 plaque-forming units (pfu)/mL at 3 days postinoculation (PI). Corneas procured from donors were incubated in culture dishes containing WNV for 1-5 days and tested for evidence of WNV. Viral RNA and antigen were detected, and the virus reached a mean peak titer of 4.9 * 104 pfu/mL at 5 days PI. Mice were inoculated intraperitoneally with WNV, and their eyes were harvested at 2, 5, and 8 days PI and tested for evidence of WNV. Viral RNA was detected in corneas of four of nine systemically infected mice as early as 2 days PI. We conclude that human corneal cells support WNV replication in vitro and ex vivo, and WNV may disseminate into the corneas of experimentally infected mice. These findings indicate that corneal transmission cannot be ruled out as a novel mode of human-to-human WNV transmission and additional experiments should be conducted to assess this risk further. PMID- 27672206 TI - Hymenolepis nana Impact Among Children in the Highlands of Cusco, Peru: An Emerging Neglected Parasite Infection. AB - Hymenolepis nana is the most common cestode infection in the world. However, limited information is available regarding its impact on affected populations. We studied the epidemiology and symptoms associated with hymenolepiasis among children 3-16 years old in 16 rural communities of the highlands of the Cusco region in Peru. Information on demographics, socioeconomic status, symptoms as reported by parents, and parasitological testing was obtained from the database of an ongoing Fasciola hepatica epidemiologic study. A total of 1,230 children were included in the study. Forty-five percent were infected with at least one pathogenic intestinal parasite. Giardia spp. (22.9%) was the most common, followed by Hymenolepis (17.4%), Fasciola (14.1%), Ascaris lumbricoides (6.1%), and Strongyloides stercoralis (2%). The prevalence of Hymenolepis infection varied by community, by other parasitic infections, and by socioeconomic status. However, only years of education of the mother, use of well water, and age less than 10 years were associated with Hymenolepis infection in the multivariate analysis. Hymenolepis nana infection was associated with diarrhea, jaundice, headaches, fever, and fatigue. Children with > 500 eggs/g of stool were more likely to have symptoms of weight loss, jaundice, diarrhea, and fever. Hymenolepis nana infection and age were the only factors retained in the multivariate analysis modeling diarrhea. Hymenolepiasis is a common gastrointestinal helminth in the Cusco region and is associated with significant morbidity in children in rural communities. The impact caused by the emergence of Hymenolepis as a prevalent intestinal parasite deserves closer scrutiny. PMID- 27672207 TI - Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda. AB - Despite the potential benefit of primaquine in reducing Plasmodium falciparum transmission and radical cure of Plasmodium vivax and Plasmodium ovale infections, concerns over risk of hemolytic toxicity in individuals with glucose 6-phosphate dehydrogenase deficiency (G6PDd) have hampered its deployment. A cross-sectional survey was conducted in 2014 to assess the G6PDd prevalence among 631 children between 6 and 59 months of age in southwestern Uganda, an area where primaquine may be a promising control measure. G6PDd prevalence was determined using three detection methods: a quantitative G6PD enzyme activity assay (Trinity Biotech(r) G-6-PDH kit), a qualitative point-of-care test (CareStartTM G6PD rapid diagnostic test [RDT]), and molecular detection of the G6PD A- G202A allele. Qualitative tests were compared with the gold standard quantitative assay. G6PDd prevalence was higher by RDT (8.6%) than by quantitative assay (6.8%), using a < 60% activity threshold. The RDT performed optimally at a < 60% threshold and demonstrated high sensitivity (>= 90%) and negative predictive values (100%) across three activity thresholds (below 60%, 30%, and 40%). G202A allele frequency was 6.4%, 7.9%, and 6.8% among females, males, and overall, respectively. Notably, over half of the G202A homo-/hemizygous children expressed >= 60% enzyme activity. Overall, the CareStartTM G6PD RDT appears to be a viable screening test to accurately identify individuals with enzyme activities below 60%. The low prevalence of G6PDd across all three diagnostic modalities and absence of severe deficiency in our study suggests that there is little barrier to the use of single-dose primaquine in this region. PMID- 27672208 TI - Post-Kala-Azar Dermal Leishmaniasis Without Previous History of Visceral Leishmaniasis. AB - Post-kala-azar dermal leishmaniasis (PKDL) without previous visceral leishmaniasis (VL) is a rare dermatological manifestation of Leishmania infection. To date, most of the reported cases neither showed parasitological confirmation nor explained the outcome of treatment. Herein, we report three confirmed cases that were were successfully cured after miltefosine treatment. PMID- 27672209 TI - Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation. AB - NADH-ubiquinone oxidoreductase (complex I) is the largest (~1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. PMID- 27672212 TI - David Spector: Coordinating gene expression in space and time. PMID- 27672210 TI - Class I Histone Deacetylase HDAC1 and WRN RECQ Helicase Contribute Additively to Protect Replication Forks upon Hydroxyurea-induced Arrest. AB - The WRN helicase/exonuclease is mutated in Werner syndrome of genomic instability and premature aging. WRN-depleted fibroblasts, although remaining largely viable, have a reduced capacity to maintain replication forks active during a transient hydroxyurea-induced arrest. A strand exchange protein, RAD51, is also required for replication fork maintenance, and here we show that recruitment of RAD51 to stalled forks is reduced in the absence of WRN. We performed a siRNA screen for genes that are required for viability of WRN-depleted cells after hydroxyurea treatment, and identified HDAC1, a member of the class I histone deacetylase family. One of the functions of HDAC1, which it performs together with a close homolog HDAC2, is deacetylation of new histone H4 deposited at replication forks. We show that HDAC1 depletion exacerbates defects in fork reactivation and progression after hydroxyurea treatment observed in WRN- or RAD51-deficient cells. The additive WRN, HDAC1 loss-of-function phenotype is also observed with a catalytic mutant of HDAC1; however, it does not correlate with changes in histone H4 deacetylation at replication forks. On the other hand, inhibition of histone deacetylation by an inhibitor specific to HDACs 1-3, CI-994, correlates with increased processing of newly synthesized DNA strands in hydroxyurea-stalled forks. WRN co-precipitates with HDAC1 and HDAC2. Taken together, our findings indicate that WRN interacts with HDACs 1 and 2 to facilitate activity of stalled replication forks under conditions of replication stress. PMID- 27672211 TI - EPR studies of wild type and mutant Dre2 identify essential [2Fe--2S] and [4Fe- 4S] clusters and their cysteine ligands. AB - Yeast Dre2 (anamorsin or CIAPIN1) is an essential component for cytosolic Fe/S cluster biosynthesis. The C-terminal domain contains eight evolutionarily conserved cysteine residues, and we previously demonstrated that the yeast Dre2 overexpressed in Escherichia coli contains one binuclear ([2Fe-2S]) cluster and one tetranuclear ([4Fe-4S]) cluster. In this study, we replaced each conserved cysteine with alanine and analyzed the effects by Electron Paramagnetic Resonance. Although the C311A mutant lacked both signals, our data clearly suggest that the [2Fe-2S] cluster is ligated to Cys252, Cys263, Cys266 and Cys268, whereas the [4Fe-4S] cluster is ligated to Cys311, Cys314, Cys322 and Cys325. By simulation analysis of the C263A and C322A data, we obtained the g values for the [4Fe-4S] cluster (gx,y,z = 1.830, 1.947 and 2.018) and for the [2Fe-2S] cluster (gx,y,z =1.919, 1.962 and 2.001). We also observed spin-spin interaction between the two clusters, suggesting their close proximity. Chemically reconstituted Dre2 showed air sensitivity of the [4Fe-4S] cluster converting to a [2Fe-2S] cluster. Furthermore, using a yeast shuffle strain, we demonstrated for the first time that each of the Cys Fe-S cluster ligands with the exception of C252 is essential, indicating that both Dre2 clusters are needed for cell viability. PMID- 27672213 TI - Blood flow boosts BMP signaling to keep vessels in shape. AB - Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201603106) show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby establishing endothelial quiescence. PMID- 27672214 TI - Diluted honey inhibits biofilm formation: potential application in urinary catheter management? AB - AIMS: Biofilms are ubiquitous and when mature have a complex structure of microcolonies in an extracellular polysaccharide and extracellular DNA matrix. Indwelling medical devices harbour biofilms which have been shown to cause infections and act as reservoirs for pathogens. Urinary catheters are often in place for considerable periods of time and are susceptible to both encrustation and biofilm formation. Strategies for minimising biofilm occurrence underpin an active research area in biomedicine. Manuka honey has, inter alia, well established antibacterial properties. This study aims to assess the influence of honey on early biofilm formation in an established in vitro model. METHODS: An established model of early biofilm formation using static bacterial cultures in vinyl 96-well plates was used to grow Escherichia coli, strain ATC 25922 and Proteus mirabilis, strain 7002. Planktonic cells were removed and the residual biofilm was stained with crystal violet, which were subsequently eluted and quantified spectrophotometrically. Manuka honey (Unique Manuka Factor 15+) was added either with the bacteria or up to 72 hours after. RESULTS: Biofilms in this model was developed over 3 days, after which growth stalled. Mixed (1:1) cultures of E. coli and P. mirabilis grew slower than monocultures. In mixed cultures, honey gave a dose-dependent reduction in biofilm formation (between 3.3 and 16.7%w/v). At 72 hours, all concentrations inhibited maximally (p<0.001). Application of honey to cultures after 24 and 48 hours also reduced the adherent bacterial biomass (p<0.05-p<0.01). CONCLUSION: Manuka honey at dilutions as low as 3.3% w/v in some protocols and at 10% or above in all protocols tested significantly inhibits bacterial attachment to a vinyl substrate and reduces further early biofilm development. No augmentation of growth over untreated controls was observed in any experiment. PMID- 27672215 TI - Targeted next-generation sequencing of FNA-derived DNA in pancreatic cancer. AB - To improve the diagnostic value of fine-needle aspiration (FNA)-derived material, we perform targeted next-generation sequencing (NGS) in patients with a suspect lesion of the pancreas. The NGS analysis can lead to a change in the treatment plan or supports inconclusive or uncertain cytology results. We describe the advantages of NGS using one particular patient with a recurrent pancreatic lesion 7 years after resection of a pancreatic ductal adenocarcinoma (PDAC). Our NGS analysis revealed the presence of a presumed second primary cancer in the pancreatic remnant, which led to a change in treatment: resection with curative intend instead of palliation. Additionally, NGS identified an unexpected germline CDKN2A 19-base pair deletion, which predisposed the patient to developing PDAC. Preoperative NGS analysis of FNA-derived DNA can help identify patients at risk for developing PDAC and define future therapeutic options. PMID- 27672216 TI - HPV self-sampling in CIN2+ detection: sensitivity and specificity of different RLU cut-off of HC2 in specimens from 786 women. AB - AIMS: Mortality for cervical cancer varies between the different regions of the world, with high rates in low-income countries where screening programmes are not present and organised. However, increasing screening coverage is still a priority in all countries: one way to do that is to base screening on self-sampled screening. The success of a self-sampling screening strategy depends on capacity to recruit unscreened women, on the performance and acceptability of the device and on the clinical performance of the high-risk human papillomavirus (HPV) test. METHODS: This study based on 786 enrolled women investigates the best cut-off value of Hybrid Capture 2 HPV test (HC2) for self-sampled specimens in terms of sensitivity and specificity. RESULTS: In this population, we found that the sensitivity and the specificity for cervical intraepithelial neoplasia grade 2 or more detection of HC2 performed on self-sampled specimens were 82.5% and 82.8%, respectively considering the relative light units (RLU) cut-off value of 1. Increasing the cut-off value the sensitivity decreases and the specificity raises and the best area under the curve for the RLU cut-off value is 1. CONCLUSIONS: Our results confirm that the cut-off value of 1 suggested by Qiagen for PreservCyt specimen is the best cut-off value also for self-sampled specimens. PMID- 27672217 TI - The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer. AB - AIMS: The study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer. METHODS: H&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N cadherin, snail-1 and vimentin) was performed. The miRNA-21 expression levels were determined using qRT-PCR and the data was analysed using the relative quantification method. The Fisher's exact and Pearson's chi2 tests were used to correlate snail-1, E-cadherin, miRNA-21 and clinicopathological data. RESULTS: Our results showed a statistically significant correlation between high miRNA-21 expression levels and E-cadherin positive cases. There was also an association between high miRNA-21 expression levels and negative snail-1 expression. No significant correlation was seen between miRNA-21 expression levels and clinicopathological features. Moreover, high expression levels of miRNA-21 were significantly associated with the sporadic cases. CONCLUSIONS: Our data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease. PMID- 27672218 TI - RRT in AKI: Start Early or Wait? PMID- 27672219 TI - Glomerular Diseases: Registries and Clinical Trials. AB - Nephrology has conducted few high-quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases. PMID- 27672222 TI - UK junior doctors set for five-day strike action. PMID- 27672220 TI - Maternal morbidity and perinatal outcomes among women in rural versus urban areas. AB - BACKGROUND: Most studies examining geographic barriers to maternity care in industrialized countries have focused solely on fetal and neonatal outcomes. We examined the association between rural residence and severe maternal morbidity, in addition to perinatal mortality and morbidity. METHODS: We conducted a retrospective population-based cohort study of all women who gave birth in British Columbia, Canada, between Jan. 1, 2005, and Dec. 31, 2010. We compared maternal mortality and severe morbidity (e.g., eclampsia) and adverse perinatal outcomes (e.g., perinatal death) between women residing in areas with moderate to no metropolitan influence (rural) and those living in metropolitan areas or areas with a strong metropolitan influence (urban). We used logistic regression analysis to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found a significant association between death or severe maternal morbidity and rural residence (adjusted OR 1.15, 95% CI 1.03-1.28). In particular, women in rural areas had significantly higher rates of eclampsia (adjusted OR 2.70, 95% CI 1.79-4.08), obstetric embolism (adjusted OR 2.16, 95% CI 1.14-4.07) and uterine rupture or dehiscence (adjusted OR 1.96, 95% CI 1.42 2.72) than women in urban areas. Perinatal mortality did not differ significantly between the study groups. Infants in rural areas were more likely than those in urban areas to have a severe neonatal morbidity (adjusted OR 1.14, 95% CI 1.02 1.29), to be born preterm (adjusted OR 1.06, 95% CI 1.01-1.11), to have an Apgar score of less than 7 at 5 minutes (adjusted OR 1.24, 95% CI 1.13-1.31) and to be large for gestational age (adjusted OR 1.14, 95% CI 1.10-1.19). They were less likely to be small for gestational age (adjusted OR 0.90, 95% CI 0.85-0.95) and to be admitted to an neonatal intensive care unit (NICU) (adjusted OR 0.36, 95% CI 0.33-0.38) compared with infants in urban areas. INTERPRETATION: Compared with women in urban areas, those in rural areas had higher rates of severe maternal morbidity and severe neonatal morbidity, and a lower rate of NICU admission. Maternity care providers in rural regions need to be aware of potentially life threatening maternal and perinatal complications requiring advanced obstetric and neonatal care. PMID- 27672221 TI - Reining in the "100-day cough": unfinished business. PMID- 27672223 TI - Parliament to vote on palliative care bill. PMID- 27672224 TI - Saskatchewan won't declare HIV emergency. PMID- 27672226 TI - Doing the right thing for our patients with disabilities. PMID- 27672225 TI - Effectiveness of pertussis vaccination and duration of immunity. AB - BACKGROUND: A resurgence of pertussis cases among both vaccinated and unvaccinated people raises questions about vaccine effectiveness over time. Our objective was to study the effectiveness of the pertussis vaccine and characterize the effect of waning immunity and whole-cell vaccine priming. METHODS: We used the test-negative design, a nested case-control study with test negative individuals as controls. We constructed multivariable logistic regression models to estimate odds ratios (ORs). Vaccine effectiveness was calculated as (1 - OR) * 100. We assessed waning immunity by calculating the odds of developing pertussis per year since last vaccination and evaluated the relative effectiveness of priming with acellular versus whole-cell vaccine. RESULTS: Between Dec. 7, 2009, and Mar. 31, 2013, data on 5867 individuals (486 test-positive cases and 5381 test-negative controls) were available for analysis. Adjusted vaccine effectiveness was 80% (95% confidence interval [CI] 71% to 86%) at 15-364 days, 84% (95% CI 77% to 89%) at 1-3 years, 62% (95% CI 42% to 75%) at 4-7 years and 41% (95% CI 0% to 66%) at 8 or more years since last vaccination. We observed waning immunity with the acellular vaccine, with an adjusted OR for pertussis infection of 1.27 (95% CI 1.20 to 1.34) per year since last vaccination. Acellular, versus whole-cell, vaccine priming was associated with an increased odds of pertussis (adjusted OR 2.15, 95% CI 1.30 to 3.57). INTERPRETATION: We observed high early effectiveness of the pertussis vaccine that rapidly declined as time since last vaccination surpassed 4 years, particularly with acellular vaccine priming. Considering whole-cell vaccine priming and/or boosters in pregnancy to optimize pertussis control may be prudent. PMID- 27672227 TI - Well-differentiated thyroid cancer: Thyroidectomy or lobectomy? PMID- 27672228 TI - Cardiopulmonary resuscitation. PMID- 27672229 TI - Greedy Spouse, Needy Parent: The Marital Dynamics of Gay, Lesbian, and Heterosexual Intergenerational Caregivers. AB - It is well established that married heterosexual women do more intergenerational caregiving for aging parents and parents-in-law than married heterosexual men do. However, gay men and lesbian women's recent access to marriage presents new questions about the gendered marital dynamics of intergenerational caregiving. We use dyadic data with gay, lesbian, and heterosexual spouses to examine the marital dynamics of intergenerational caregivers. Results show that gay and lesbian spouses provided intensive time and emotional support for an intergenerational caregiver. In contrast, heterosexual women described their intergenerational caregiving as rarely supported and at times even undermined by their spouse. Dyadic data on heterosexual men corroborate women's accounts; heterosexual men rarely reported providing intergenerational caregiving, and thus heterosexual women rarely described providing spousal support. These findings provide new insight into the intermingled roles of "greedy" marriages and "needy" parents, wherein marital negotiations around caregiving vary by gender for gay, lesbian, and heterosexual marital dyads. PMID- 27672230 TI - Optical method for automated measurement of glass micropipette tip geometry. AB - Many experimental biological techniques utilize hollow glass needles called micropipettes to perform fluid extraction, cell manipulation, and electrophysiological recordings For electrophysiological recordings, micropipettes are typically fabricated immediately before use using a "pipette puller", which uses open-loop control to heat a hollow glass capillary while applying a tensile load. Variability between manufactured micropipettes requires a highly trained operator to qualitatively inspect each micropipette; typically this is achieved by viewing the pipette under 40-100x magnification in order to ensure that the tip has the correct shape (e.g., outer diameter, cone angle, taper length). Since laboratories may use hundreds of micropipettes per week, significant time demands are associated with micropipette inspection. Here, we have automated the measurement of micropipette tip outer diameter and cone angle using optical microscopy. The process features repeatable constraint of the micropipette, quickly and automatically moving the micropipette to bring its tip into the field of view, focusing on the tip, and computing tip outer diameter and cone angle measurements from the acquired images by applying a series of image processing algorithms. As implemented on a custom automated microscope, these methods achieved, with 95% confidence, +/-0.38 um repeatability in outer diameter measurement and +/-5.45 degrees repeatability in cone angle measurement, comparable to a trained human operator. Accuracy was evaluated by comparing optical pipette measurements with measurements obtained using scanning electron microscopy (SEM); optical outer diameter measurements differed from SEM by 0.35 +/- 0.36 um and optical cone angle measurements differed from SEM by -0.23 +/- 2.32 degrees . The algorithms we developed are adaptable to most commercial automated microscopes and provide a skill-free route to rapid, quantitative measurement of pipette tip geometry with high resolution, accuracy, and repeatability. Further, these methods are an important step toward a closed-loop, fully-automated micropipette fabrication system. PMID- 27672231 TI - Ownership of a bank account and health of older Hispanics. AB - We study health effects of financial inclusion, particularly ownership of a checking account of older minorities, with focus on Hispanics. Using data from the Health and Retirement Study from 2000 to 2012, we find that, for Hispanics, being banked has a positive effect on mental health but is not associated with effects on physical health. Mental health benefits are likely to be larger for those who face greater hurdles to access formal financial institutions. Hispanics in less well-off neighborhoods and with below-median wealth appear to experience the greatest mental-health benefits associated with ownership of a checking account. PMID- 27672232 TI - Design and Evaluation of an Actuated Exoskeleton for Examining Motor Control in Stroke Thumb. AB - Chronic hand impairment is common following stroke. This paper presents an actuated thumb exoskeleton (ATX) to facilitate research in examining motor control and hand rehabilitation. The ATX presented in this work aims to provide independent bi-directional actuation in each of the 5 degrees-of-freedom (DOF) of the thumb using a novel flexible shaft based mechanism that has 5 active DOF and 3 passive DOF. A prototype has been built and experiments have been conducted to measure the allowable workspace at the thumb and evaluate the kinematic and kinetic performance of the ATX. The experimental results show that the ATX is able to provide individual actuation at all 5 thumb joints with high joint velocity and torque capacities. Further improvement and future work are discussed. PMID- 27672233 TI - The "Dirty Liver" as a Coincidental Finding on Sonography: Sonographic Criteria for Biliary Microhamartomas of the Liver. AB - OBJECTIVES: Biliary microhamartomas of the liver are known as symptomless, benign, microscopic biliary duct deformations. The consistently improving quality of ultrasound technology has made it possible to visualize them, which has led to difficulty in distinguishing them from neoplastic liver alterations. The purpose of this study was to evaluate the appearance of biliary microhamartomas and their behavior on contrast-enhanced sonography. METHODS: We defined typical sonographic findings in biliary microhamartomas of the liver (1 main criterion and 3 secondary criteria). Nineteen patients were identified as have typical characteristics images of biliary microhamartomas as coincidental findings on liver sonography. All patients were included in a clinical follow-up program without histologic confirmation after they underwent risk assessment. Follow-up examinations were performed with B-mode sonographic examinations at 6, 12, and 18 months. In addition, in 15 patients, contrast-enhanced sonographic examinations of the liver were performed. RESULTS: None of the patients had a change in the number or size of the identifiable typical liver lesions (main criterion) after a mean follow-up period +/- SD of 14.4 +/- 6.5 months. There were also no alterations among the aforementioned secondary criteria in any of the participants. On contrast-enhanced sonography, the lesions of all patients showed a consistent pattern, with early arterial enrichment and persistent homogeneous contrast in the late portal venous phase. CONCLUSIONS: The sonographic appearance of biliary microhamartomas is characteristic and typical enough that histologic confirmation is not always necessary. Follow-up examinations to monitor any developments are usually adequate. PMID- 27672234 TI - Contrast-Enhanced Sonography and Fusion Technology for Assessment of an Embolized Renal Angiomyolipoma. PMID- 27672235 TI - Second-Trimester Sonographic Diagnosis of Polymicrogyria. PMID- 27672236 TI - A 176-Channel 0.5cm3 0.7g Wireless Implant for Motor Function Recovery after Spinal Cord Injury. PMID- 27672237 TI - Environmental, behavioral, and psychological predictors of transit ridership: Evidence from a community intervention. AB - Understanding who takes advantage of new transit (public transportation) interventions is important for personal and environmental health. We examine transit ridership for residents living near a new light rail construction as part of "complete street," pedestrian-friendly improvements. Adult residents (n=536) completed surveys and wore accelerometer and GPS units that tracked ridership before and after new transit service started. Transit riders were more physically active. Those from environments rated as more walkable were likely to be continuing transit riders. Place attachment, but not perceived physical incivilities on the path to transit, was associated with those who continued to ride or became new riders of transit. This effect was mediated through pro-city attitudes, which emphasize how the new service makes residents eager to explore areas around transit. Thus, place attachment, along with physical and health conditions, may be important predictors and promoters of transit use. PMID- 27672238 TI - TBL1XR1 Is Highly Expressed in Gastric Cancer and Predicts Poor Prognosis. AB - Objective. To investigate the expression of transducin- (beta-) like 1 X-linked receptor 1 (TBL1XR1) in human gastric cancer (GC) and its correlation with prognostic and biologic significance. Methods. TBL1XR1 mRNA expression was analyzed in gastric cancer using a microarray dataset (GSE2701) from the Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) analysis of TBL1XR1 was performed on GC tissue microarray (TMA) to assess its prognostic and biological significance in 334 patients of GC. Results. Analysis of GSE2701 showed that the mRNA levels of TBL1XR1 were significantly elevated in primary gastric tumor and lymph node tissues than normal gastric tissues (P < 0.05). The same results of TBL1XR1 protein level were observed by IHC staining in 334 GC tissues. 204 of 334 (60.1%) primary gastric cancer tissues showed high expression of TBL1XR1 protein. TBL1XR1 overexpression was significantly correlated with lymph node metastasis (P = 0.000) and advanced TNM stage (P = 0.001). Moreover, high levels of TBL1XR1 predicted worse overall survival (P = 0.015). Multivariate Cox regression analysis indicated that high expression of TBL1XR1 was an independent prognostic factor for poor overall survival (HR, 0.525; 95% confidence interval, 0.367 0.752; P = 0.005). Conclusion. This present study demonstrates that TBL1XR1 is overexpressed in gastric cancer and may be a potential predictor and therapeutic target for GC patients. PMID- 27672239 TI - Opioid Overdose Experience, Risk Behaviors, and Knowledge in Drug Users from a Rural versus an Urban Setting. AB - BACKGROUND: Opioid use is highly prevalent in the United States and there has been an increased incidence in the rate of opioid-related overdose. While evidence suggests there are substantial differences in opioid use among rural versus urban settings, the rate of overdose and corresponding frequency of opioid overdose risk behaviors and overdose knowledge between rural and urban settings have not been examined. METHODS: Individuals with opioid use disorder from rural (N=98) and urban (N=247) settings completed a self-report survey regarding their lifetime history of overdose and overdose risk behaviors. Participants also completed the Brief Opioid Overdose Knowledge (BOOK) questionnaire, a 12-item self-report measure of opioid overdose knowledge. RESULTS: Overall, 35.6% of participants had experienced an overdose, and prevalence of overdose was significantly higher (p<.01) among rural (45.9%) vs. urban (31.6%) participants, though fewer rural participants reported past 30-day risk behaviors. There were few differences observed between the subset of rural and urban participants who had experienced an overdose, and fewer rural participants with a history of overdose reported past 30-day risk behaviors. Both rural and urban participants performed poorly on the BOOK, though the percent of correct responses was lowest among rural participants with a history of overdose. CONCLUSION: Results demonstrate higher rates of overdose among rural opioid users, though rural participants were less likely to report recent risk behaviors. Results also suggest that knowledge regarding key factors related to opioid overdose is severely lacking, particularly among rural opioid users, which could be a potential target for future intervention efforts. PMID- 27672240 TI - The Relation of Drug Trafficking Fears and Cultural Identity to Attitudes Toward Mexican Immigrants in Five South Texas Communities. AB - This paper reports the findings of research investigating the relationship of spill-over fears related to drug trafficking and of cultural identity to Mexican Americans' attitudes toward recent immigrants from Mexico in five non metropolitan communities in the US-Mexico borderlands of South Texas. A mixed methods design was used to collect data from 91 participants (30 intact families with two parents and at least one young adult). Quantitative findings showed that the majority of participants expressed the view that most people in their communities believed that newcomers were involved in drug trafficking and in defrauding welfare programs. A significant interaction indicated that Mexican cultural identity buffered the negative effects of drug trafficking fears as related to the view that the newcomers were creating problems in the communities and region. Qualitative data yielded positive and negative themes, with those that were negative being significantly more numerous. The findings have implications for intra-ethnic relations in borderlands communities as well as for immigration policy. PMID- 27672242 TI - Circulating Calreticulin Is Increased in Myelofibrosis: Correlation with Interleukin-6 Plasma Levels, Bone Marrow Fibrosis, and Splenomegaly. AB - Myelofibrosis (MF) is a clonal neoplasia of the hemopoietic stem/progenitor cells associated with genetic mutations in the Janus kinase 2 (JAK2), myeloproliferative leukemia virus oncogene (MPL), and calreticulin (CALR) genes. MF is also characterized by a state of chronic inflammation. Calreticulin (CRT), as a multifunctional protein, is involved in a spectrum of cellular processes including inflammation, autoimmunity, and cancer initiation/progression. Based on this background, we hypothesised that in MF circulating CRT might reflect the inflammatory process. In the present study we show that circulating CRT is increased in MF patients compared to healthy controls. Also, in MF, CRT levels highly correlate with bone marrow fibrosis, splenomegaly, and Interleukin-6 (IL 6) plasma levels. In turn, higher IL-6 levels also correlated with disease severity in terms of increased spleen size, bone marrow fibrosis, number of circulating CD34+ cells, and lower hemoglobin values. These results demonstrate that the circulating CRT takes part in the inflammatory network of MF and correlates with aggressiveness of the disease. PMID- 27672243 TI - A novel fresh cadaver model for education and assessment of joint aspiration. AB - OBJECTIVES: The objective of this study was to describe a novel cadaver model and to determine the utility of this model for teaching and assessing students in performing knee, elbow, and wrist arthrocentesis. METHODS: Third year medical students were evaluated while performing arthrocentesis during a fresh cadaver training sessions. RESULTS: Sixty-three participants were included in this analysis. There was statistically significant improvement between the pre- and post-test analysis in all aspects assessed in our study of elbow, knee and wrist arthrocentesis. CONCLUSIONS: The use of fresh cadavers for the education and assessment of arthrocenteses is an effective training model. PMID- 27672241 TI - Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1beta Production. AB - IL-1beta is one of the main proinflammatory cytokines that regulates a broad range of immune responses and also participates in several physiological processes. The canonical production of IL-1beta requires multiprotein complexes called inflammasomes. One of the most intensively studied inflammasome complexes is the NLRP3 inflammasome. Its activation requires two signals: one signal "primes" the cells and induces the expression of NLRP3 and pro-IL-1beta, while the other signal leads to the assembly and activation of the complex. Several stimuli were reported to function as the second signal including reactive oxygen species, lysosomal rupture, or cytosolic ion perturbation. Despite very intensive studies, the precise function and regulation of the NLRP3 inflammasome are still not clear. However, many chronic inflammatory diseases are related to the overproduction of IL-1beta that is mediated via the NLRP3 inflammasome. In this review, we aimed to provide an overview of studies that demonstrated the effect of plant-derived natural compounds on NLRP3 inflammasome-mediated IL-1beta production. Although many of these studies lack the mechanistic explanation of their action, these compounds may be considered as complementary supplements in the treatment of chronic inflammatory diseases, consumed as preventive agents, and may also be considered as molecular tools to study NLRP3 function. PMID- 27672245 TI - International Caries Detection and Assessment System (ICDAS): A New Concept. AB - Dental caries is a complex multifactorial disease of the calcified tissues of the teeth, caused by interaction of various factors including the host, agent, substrate and time as demonstrated by the Keyes circle. Detecting carious lesion at the earliest possible stage of its development is definitely helpful in appropriate treatment planning for the same. The lack of consistency among the contemporary criteria systems for detecting carious lesions limits the comparability of outcomes measured in epidemiological and clinical studies. Therefore, the ICDAS criteria was developed by an international team of caries researchers to integrate several new criteria systems into one standard system for caries detection and assessment. It is a clinical scoring system for use in dental education, clinical practice, research, and epidemiology, and provides a framework to support and enable personalized total caries management for improved long-term health outcomes. PMID- 27672244 TI - Gene Therapy and its Implications in Dentistry. AB - BACKGROUND: The concept of transferring genes to tissues for clinical applications has been discussed for nearly half a century. The exponential increase in our ability to manipulate the genetic material of a cell via recombinant DNA technology has brought this goal closer to realization. The original perception that gene therapy should be considered only for a few major organs as a means of treating life-threatening disorders that are refractory to conventional treatment has changed. There are many non-life-threatening conditions that adversely affect a patient's quality of life, for which there are no effective treatments. The lack of suitable treatment has permitted morbidity to become a rational basis for extending the scope of gene therapy. In the past few years, remarkable progress has been made in the field of gene therapy. While considerable problems remain, thus impeding the routine clinical use of gene transfer, gene therapy will have a pervasive and significant impact on areas that are based on biological science. AIM: The purpose of this review is to examine the progress made in addressing gene transfer strategies for correcting various diseases and problems that are relevant to dental practice. PMID- 27672246 TI - Pediatric Dental Trauma:Wide Horizon of Ignored Etiological Factors. AB - Trauma of the oral and peroral structures are one of the most common and frequent complaints after dental caries with which a child is being referred to a dental clinic. As an emergency, we tend to treat the injuries without understanding or neglecting the cause of trauma. The different possible etiological factors are unnoticed, not revealed or not noted while taking the history of the patient. Sometimes negligence of the etiology by the dentist himself or the accompanying person could influence the prognosis and prevention. Thus, this paper is an effort towards exploring the common yet unnoticed etiological factors of pediatric dental trauma which we tend to knowingly ignore. PMID- 27672247 TI - Dentition Status and Oral Health Practice among Hearing and Speech-Impaired Children:A Cross-sectional Study. AB - The main aim of this study was to assess the oral health status and oral hygiene practices in children with impaired hearing and speech. A total of 76 children in the age group of 5 to 18 years of both sexes were surveyed and information about their oral hygiene practices, previous dental visit and oral health knowledge were obtained through a questionnaire. Around 61% of the children had never visited a dentist, 82.89% and 17.11% of them brushed once and twice daily respectively. More than 90% of them cared about their teeth as much as any other part of the body. 42% of the children had dental caries, and gingivitis was seen in 35% of the children and malocclusion in 19% of them. PMID- 27672248 TI - Perception of Facial Profile: How You Feel About Yourself. AB - OBJECTIVE: The aim of this study was to determine how aware the individuals were of their own profile and to compare the orthodontist's perception of an attractive facial profile with those of laypeople, dental students and orthodontic patients. MATERIALS AND METHODS: The study comprised of a total of 200 subjects divided into four groups of 50 subjects each: Laypeople, first-year dental students, final-year dental students and orthodontic patients. Participants answered a questionnaire regarding facial profile and their expectations from orthodontic treatment. The facial profile photographs of participants were analyzed by two orthodontists separately who matched the individual to the depicted silhouettes. Agreement between participants and orthodontists was evaluated by using the statistic chi(2) test. RESULTS: Dental students and orthodontic patients were more aware of their facial profile as compared to the laypeople. The four groups were different in their abilities to recognize their own profiles. The difference in profile perception between orthodontists and subjects was statistically significant (p < 0.05). CONCLUSIONS: Class I profiles were perceived to be the most attractive by all the groups and profiles with a protrusive mandible were perceived to be the least attractive. Final-year dental students and orthodontic patients were more accurate in identifying their own profile. PMID- 27672249 TI - An Innovative Miniature Bite Force Recorder. AB - In this study, a detailed description of development of a new novel bite force recorder (gnathodynamometer) using solid state components is vividly explained. This state of the art authenticated device can be used to assess the complex function of human bite force, which is the net resultant combination of functional response of various craniomandibular structures consisting of interrelated components, like the muscles of mastication, joints, teeth and the neuromuscular system. The consistency and accuracy of the bite force recorder was reaffirmed by doing a detailed laboratory calibration and clinical testing on 30 adult subjects. PMID- 27672251 TI - Osteomyelitis of Maxilla in Infantile Osteopetrosis: A Case Report with Review of Literature. AB - Osteopetrosis is a rare genetic disorder that causes generalized sclerosis of bone due to a defect in bone resorption and remodeling. It is usually manifesting in two basic forms: An autosomal dominant benign form (osteopetrosis tarda) and an autosomal recessive malignant form (osteopetrosis congenita). A third form, the intermediate recessive type, has also been reported. Dental abnormality may be attributed to pathological changes in bone remodeling. Osteomyelitis is well documented as a complication of osteopetrosis and is severe and difficult to treat. This is a case of 8-year-old boy with osteopetrosis presenting with the complaint of swelling of left side of face. PMID- 27672250 TI - Sugar-Sweetened Beverages: General and Oral Health Hazards in Children and Adolescents. AB - Ubiquitously unhealthy eating and drinking habits and the development of multiple morbidities, including obesity, type-2 diabetes, dental caries and dental erosion have become a major challenge for physicians, dentists and parents. Modernization has provided heaps of option for outdoor eating and sugar-containing drinks. Even the "diet" labeled drinks are considered not free from sugars and enhances calorie input. With the increasing trends of eating unhealthy, sticky and readily available, refined carbohydrate-rich foods and drinks, problems pertaining to body's metabolic activity and oral health have also been significantly recognized. Dentists and pediatricians can play a pivotal role and should emphasize on patients' education and counseling on the proper nutritional diet and health. PMID- 27672252 TI - Modified Intraoral Repositioning Appliance in Complete Bilateral Cleft Lip and Palate. AB - OBJECTIVE: The purpose of the modified repositioning appliance was to overcome the shortcoming of existing design for repositioning protruded premaxilla in a child with bilateral cleft lip and palate. METHODS: The basic principles of design were similar to Latham's appliance but the surgical pinning of premaxillary segment was avoided and instead acrylic splint was prepared. CONCLUSIONS: This technique avoids any invasive procedure, is useful to reposition protruded premaxillary segment in bilateral cleft lip and palate cases specifically in child who reports late with deciduous dentition. PMID- 27672253 TI - Maryland Bridge: An Interim Prosthesis for Tooth Replacement in Adolescents. AB - A space in the anterior region of the dental arch of a youngster, either due to trauma or a congenitally missing tooth, can not only lead to psychological trauma but also create a functional dilemma for the dentist, as the usual treatment options of implant, removable partial denture and fixed partial denture available for adults, are often inapplicable or inconvenient for an adolescent. In such a situation, a resin-bonded fixed partial denture (RBFPD), such as Maryland Bridge fulfills all the requirements of an ideal interim solution till growth completion is achieved and a more permanent tooth replacement option can be explored. PMID- 27672254 TI - Type III Dens Invaginatus with an Associated Cyst: A Case Report and Literature Review. AB - Dens invaginatus (dens in dente) is a rare malformation with a widely varied morphology. An unusual presentation of a type III dens invaginatus affecting a conical shaped permanent lateral incisor in an 8-year-old female patient is reported. The presence of a pulp stone and a periapical radiolucency further added onto the complexity of the case. The etiology, pathophysiology, association with other dental anomalies as well as the challenges in management of this anomaly are discussed. An extensive literature review is also presented. PMID- 27672255 TI - Temporary Anchorage Device: An Epitome of Anchorage in Orthodontic Treatment. AB - One of the most important phases of oral health is the form and function of the oral mechanism. Recently, pediatric dentists are concerned with the obvious esthetic disabilities and the pathologic implications of the malposed teeth. Interceptive and functional orthodontic treatment is playing a major role in these discrepancies. Anchorage is an important consideration in orthodontics, particularly if force is applied entirely to the teeth. For many years, clinicians have searched for a form of anchorage that does not rely on patient cooperation. During the last few decades, a wealth of new information has accumulated to such an extent that the present authors thought it appropriate to let these advances make an impact by suggesting a revised definition and classification of anchorage. This paper also gives a brief insight on evolution of anchorage and its application in pediatric dentistry. PMID- 27672256 TI - Management of a Dentigerous Cyst: A Two-Year Review. AB - Dentigerous cyst is reported to be one of the most common odontogenic cysts of the jaws.(12) The most commonly involved teeth are mandibular third molars, maxillary canines, maxillary third molars and rarely maxillary anteriors.(23) This case report is about the management of a dentigerous cyst associated with a mandibular second molar (37) in a 9-year-old girl by a conservative treatment plan of marsupialization of the cyst. A 2-year postsurgical review reveals complete disappearance of the cystic lesion and normal alignment of 37 and 38. PMID- 27672257 TI - Oral Rehabilitation of an S-ECC Case with Orthodontic Intervention: 18 Months Follow-up. AB - Severe-early childhood caries (S-ECC) is a specific form of rampant decay of primary teeth in infants, characterized by aggressive tooth destruction. This multifactorial disease in young infants is associated with the frequent use of sweetened fluids and fermentable carbohydrates over extended periods, poor oral hygiene as well as high level of mutans streptococci infection. The disease control and restoration of severely decayed primary teeth in children with S-ECC remains a challenge to general as well as pediatric dentists. This article portrays the oral rehabilitation of a five and half-year-old girl presenting with S-ECC with an 18 months follow-up. PMID- 27672258 TI - Regional Odontodysplasia Crossing Midline: A Rare Case Report. AB - Regional odontodysplasia is a nonhereditary, uncommon developmental abnormality of teeth. Females have more predilections for regional odontodysplasia. The enamel, dentin and pulp of teeth are affected and radiographically, teeth are described as "ghost teeth". Many of these :eeth do not erupt and have an increased risk for caries and periapical inflammation. Since the literature on regional odontodysplasia is limited, here is need to discuss this anomaly to have a better approach for the diagnosis and treatment. PMID- 27672259 TI - Beads in the Tooth. AB - Foreign objects in a tooth are often diagnosed accidentally. A detailed case history, clinical and radiographic examinations are necessary to know the exact nature, size, location of the foreign body and the difficulty involved in its retrieval. In the present case, two beads, one radiopaque and one radiolucent were found in the same tooth at different places of 11-year-old girl. Patient did not reveal proper history out of fear. Both the foreign objects were discovered during routine endodontic procedure which were removed following simple clinical procedure causing minimal damage to the internal tooth structure. PMID- 27672260 TI - Deciduous Mandibular Second Molar with Supernumerary Roots and Root Canals Associated with Missing Mandibular Permanent Premolar. AB - Morphological variations like additional roots and root canals in human deciduous dentition are rare. Knowledge of the morphology, variation of root and root canals of deciduous teeth are useful for successful endodontic treatment and exodontia. Presented here is a case report of the supernumerary roots and additional root canals of deciduous mandibular second molar (85) with congenitally bilateral missing of mandibular permanent second premolar (35 and 45) tooth bud. PMID- 27672261 TI - Amelogenesis Imperfecta: Full Mouth Rehabilitation in Deciduous Dentition. AB - This clinical report describes the oral rehabilitation of a very young child diagnosed with hypoplastic amelogenesis imperfecta. The specific treatment objectives being adequate patient management, eliminate tooth sensitivity while enhancing esthetics, masticatory function and improved self confidence. The treatment included full mouth rehabilitation with stainless steel crowns on posterior teeth and indirect composite veneers on anterior teeth. PMID- 27672262 TI - Editorial. PMID- 27672263 TI - MicroRNA biomarkers predicting risk, initiation and progression of colorectal cancer. AB - Colorectal cancer is a major global cause of morbidity and mortality. Current strategies employed to increase detection of early, curable stages of this disease are contributing to a reduction of the negative health impact from it. While there is a genetic component to the risk of disease, diet and environment are known to have major effects on the risk of an individual for developing the disease. However, there is the potential to reduce the impact of this disease further by preventing disease development. Biomarkers which can either predict the risk for or early stages of colorectal cancer could allow intervention at a time when prospects could be modified by environmental factors, including lifestyle and diet choices. Thus, such biomarkers could be used to identify high risk individuals who would benefit from lifestyle and dietary interventions to prevent this disease. This review will give an overview on one type of biomarker in the form of microRNAs, which have the potential to predict an individual's risk for colorectal cancer, as well as providing a highly sensitive and non invasive warning of disease presence and/or progression. MicroRNA biomarkers which have been studied and whose levels look promising for this purpose include MiR-18a, MiR-21, MiR-92a, MiR-135b, MiR-760, MiR-601. Not only have several individual microRNAs appeared promising as biomarkers, but panels of these may be even more useful. Furthermore, understanding dietary sources and ways of dietary modulation of these microRNAs might be fruitful in reducing the incidence and slowing the progression of colorectal cancer. PMID- 27672266 TI - Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer. AB - Accurate prediction of lymph node (LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer (EGC). However, consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search, we identified several independent variables associated with LN metastasis in EGC, which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand, even if we use these promising parameters, we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN (SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review, we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition, we evaluated the history of sentinel node navigation surgery and the usefulness for EGC. PMID- 27672264 TI - Polyphosphate and associated enzymes as global regulators of stress response and virulence in Campylobacter jejuni. AB - Campylobacter jejuni (C. jejuni), a Gram-negative microaerophilic bacterium, is a predominant cause of bacterial foodborne gastroenteritis in humans worldwide. Despite its importance as a major foodborne pathogen, our understanding of the molecular mechanisms underlying C. jejuni stress survival and pathogenesis is limited. Inorganic polyphosphate (poly P) has been shown to play significant roles in bacterial resistance to stress and virulence in many pathogenic bacteria. C. jejuni contains the complete repertoire of enzymes required for poly P metabolism. Recent work in our laboratory and others have demonstrated that poly P controls a plethora of C. jejuni properties that impact its ability to survive in the environment as well as to colonize/infect mammalian hosts. This review article summarizes the current literature on the role of poly P in C. jejuni stress survival and virulence and discusses on how poly P-related enzymes can be exploited for therapeutic/prevention purposes. Additionally, the review article identifies potential areas for future investigation that would enhance our understanding of the role of poly P in C. jejuni and other bacteria, which ultimately would facilitate design of effective therapeutic/preventive strategies to reduce not only the burden of C. jejuni-caused foodborne infections but also of other bacterial infections in humans. PMID- 27672265 TI - Human papillomavirus and gastrointestinal cancer: A review. AB - Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID- 27672268 TI - New devices and techniques for endoscopic closure of gastrointestinal perforations. AB - Gastrointestinal perforations, which need to be managed quickly, are associated with high morbidity and mortality. Treatments used to close these perforations range from surgery to endoscopic therapy. Nowadays, with the development of new devices and techniques, endoscopic therapy is becoming more popular. However, there are different indications and clinical efficacies between different methods, because of the diverse properties of endoscopic devices and techniques. Successful management also depends on other factors, such as the precise location of the perforation, its size and the length of time between the occurrence and diagnosis. In this study, we performed a comprehensive review of various devices and introduced the different techniques that are considered effective to treat gastrointestinal perforations. In addition, we focused on the different methods used to achieve successful closure, based on the literature and our clinical experiences. PMID- 27672267 TI - Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma. AB - Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammation therapies would be an ideal strategy. In this article, we will review immune checkpoint and inflammation as potential targets, as well as clinical trials and the prospects for immunotherapy in PAC. PMID- 27672269 TI - Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective. AB - The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis. PMID- 27672270 TI - Regional but fatal: Intraperitoneal metastasis in gastric cancer. AB - Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients. PMID- 27672272 TI - Split liver transplantation in adults. AB - Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID- 27672273 TI - Hepatobiliary and pancreatic ascariasis. AB - Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID- 27672271 TI - Aberrant regulation of Wnt signaling in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Several signaling pathways, including the wingless/int-1 (Wnt) signaling pathway, have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin beta1 (CTNNB1)-dependent (also known as "canonical") and CTNNB1-independent (often referred to as "non-canonical") pathways. Specifically, the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes (the cell-surface receptor complex, the cytoplasmic destruction complex and the nuclear CTNNB1/T cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported, two main non-canonical pathways, Wnt/planar cell polarity pathway and Wnt/Ca(2+) pathway, participate in the regulation of hepatocarcinogenesis. Interestingly, the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover, other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore, crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC. PMID- 27672274 TI - Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury. AB - AIM: To investigate the hepatic microcirculatory changes due to Haemoxygenase (HO), effect of HO inhibition on remote ischemic preconditioning (RIPC) and modulation of CINC. METHODS: Eight groups of animals were studied - Sham, ischemia reperfusion injury (IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion, RIPC (remote ischemic preconditioning) + IRI group, remote ischemic preconditioning in sham (RIPC + Sham), PDTC + IR (Pyridodithiocarbamate, HO donor), ZnPP + RIPC + IRI (Zinc protoporphyrin prior to preconditioning), IR-24 (45 min of ischemia followed by 24 h of reperfusion), RIPC + IR-24 (preconditioning prior to IR). After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS: Velocity of flow (160.83 +/- 12.24 MUm/s), sinusoidal flow (8.42 +/- 1.19) and sinusoidal perfusion index (42.12 +/- 7.28) in hepatic IR were lower (P < 0.05) in comparison to RIPC and PDTC (HO inducer). RIPC increased velocity of flow (328.04 +/- 19.13 MUm/s), sinusoidal flow (17.75 +/- 2.59) and the sinusoidal perfusion index (67.28 +/- 1.82) (P < 0.05). PDTC (HO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity (300.88 +/- 22.109 MUm/s), sinusoidal flow (17.66 +/- 3.71) and sinusoidal perfusion (82.33 +/- 3.5) to near sham levels. ZnPP (HO inhibition) reduced velocity of flow of RBC in the RIPC group (170.74 +/- 13.43 MUm/s and sinusoidal flow in the RIPC group (9.46 +/- 1.34). ZnPP in RIPC (60.29 +/- 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules (769.05 +/- 87.48) and sinusoids (97.4 +/- 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules (219.66 +/- 93.79) and sinusoids (25.69 +/- 9.08) (P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules (89.58 +/- 58.32) and sinusoids (17.98 +/- 11.01) (P < 0.05) reproducing the effects of RIPC. ZnPP (HO inhibition) increased venular (589.04 +/- 144.36) and sinusoidal neutrophil adhesion in preconditioned animals (121.39 +/- 30.65) (P < 0.05). IR after 24 h of reperfusion increased venular and sinusoidal neutrophil adhesion in comparison to the early phase and was significantly reduced by RIPC. Hepatocellular cell death in IRI (80.83 +/- 13.03), RIPC + IR (17.35 +/- 2.47), and PTDC + IR (11.66 +/- 1.17) reduced hepatocellular death. ZnPP + RIPC + IR (41.33 +/- 3.07) significantly increased hepatocellular death (P < 0.05 PTDC/RIPC vs ZnPP and IR). The CINC cytokine levels in sham (101.32 +/- 6.42). RIPC + sham (412.18 +/- 65.24) as compared to sham (P < 0.05). CINC levels in hepatic IR were (644.08 +/- 181.24). PDTC and RIPC CINC levels were significantly lower than hepatic IR (P < 0.05). HO inhibition in preconditioned animals with Zinc protoporphyrin increased serum CINC levels (521.81 +/- 74.9) (P < 0.05). The serum CINC levels were high in the late phase of hepatic IR (15306 +/- 1222.04). RIPC reduced CINC levels in the late phase of IR (467.46 +/- 26.06), P < 0.05. CONCLUSION: RIPC protects hepatic microcirculation by induction of HO and modulation of CINC in hepatic IR. PMID- 27672275 TI - Impact of Helicobacter pylori on the healing process of the gastric barrier. AB - AIM: To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover. METHODS: In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. RESULTS: We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway. CONCLUSION: In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier. PMID- 27672276 TI - Melatonin modulates adiponectin expression on murine colitis with sleep deprivation. AB - AIM: To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS: The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. RESULTS: Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. CONCLUSION: This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti inflammatory effects on colitis with sleep deprivation. PMID- 27672277 TI - Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication. AB - AIM: To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication. METHODS: In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS: Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (>= 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and alpha-fetoprotein than did patients exhibiting low AKR1B10 expression. CONCLUSION: Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR. PMID- 27672278 TI - Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis. AB - AIM: To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS: A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type). RESULTS: There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes (except ALB), immunological indexes, positive rates of autoantibodies (except SMA), and number of cases of patients with different ANA titers (except the group at a titer of 1:10000) significantly differed between DILI patients and PBC patients. Biochemical indexes, immunological indexes, and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes (n = 30), inflammatory cell infiltration around bile ducts (n = 29), and atypical hyperplasia of small bile ducts (n = 28). DILI manifested mainly as fatty degeneration of hepatocytes (n = 15) and spotty necrosis or loss of hepatocytes (n = 14). CONCLUSION: Although DILI and PBC share some similar laboratory tests (biochemical and immunological indexes) and pathological findings, they also show some distinct characteristics, which are helpful to the differential diagnosis of the two diseases. PMID- 27672279 TI - Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey. AB - AIM: To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. METHODS: The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. RESULTS: Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. CONCLUSION: The H. pylori clarithromycin resistance rate in Brazil is at the borderline (15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate (13.5%) is equally concerning. PMID- 27672280 TI - Clinical management of acute liver failure: Results of an international multi center survey. AB - AIM: To assess the practice of caring for acute liver failure (ALF) patients in varying geographic locations and medical centers. METHODS: Members of the European Acute Liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed, treating between 300 and 500 ALF cases and performing over 100 liver transplants (LT) for ALF annually. The questions pertained to details of the institution and their clinical activity, standards of care, referral and admission, ward- based care versus intensive care unit (ICU) as well as questions regarding liver transplantation - including criteria, limitations, and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS: The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted, treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers, particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamol-related ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals, lactulose, nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure (ICP). ICP monitoring was employed in 12 centers, with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT, with a 90% post transplant survival to hospital discharge, 42% survived with medical management alone. CONCLUSION: Alongside similarities in principles of care of ALF patients, major areas of divergence were present in key areas of diagnosis, monitoring, treatment and decision to transplant. PMID- 27672281 TI - Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life. AB - AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained. The samples were analyzed for HBsAg, anti-HBc, anti HBs, anti-HCV, and anti-HIV levels as well as subjected to a combined nucleic acid test (NAT) for HBV DNA, HCV RNA and HIV RNA. RESULTS: Samples from 404 subjects were screened (85 CHB, 116 CHC, 114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION: DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system. PMID- 27672282 TI - Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy. AB - AIM: To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models (clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration, which would help in designing new therapeutic options for the regenerative drive in difficult setup, such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS: A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS: Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION: Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety, efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy -induced liver regeneration is concerned, further research on the field should focus on the role of non parenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regeneration in the setup of parenchymal liver disease. PMID- 27672283 TI - Role of spleen elastography in patients with chronic liver diseases. AB - The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations. PMID- 27672285 TI - Biomarkers for colitis-associated colorectal cancer. AB - Patients with extensive ulcerative colitis (UC) of more than eight years duration have an increased risk of colorectal cancer. Molecular biomarkers for dysplasia and cancer could have a great clinical value in managing cancer risk in these UC patients. Using a wide range of molecular techniques - including cutting-edge OMICS technologies - recent studies have identified clinically relevant biomarker candidates from a variety of biosamples, including colonic biopsies, blood, stool, and urine. While the challenge remains to validate these candidate biomarkers in multi-center studies and with larger patient cohorts, it is certain that accurate biomarkers of colitis-associated neoplasia would improve clinical management of neoplastic risk in UC patients. This review highlights the ongoing avenues of research in biomarker development for colitis-associated colorectal cancer. PMID- 27672284 TI - Interaction of obesity and inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management. PMID- 27672286 TI - New insights into the pathophysiology of achalasia and implications for future treatment. AB - Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life. PMID- 27672287 TI - Anemia and iron deficiency in gastrointestinal and liver conditions. AB - Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice. PMID- 27672288 TI - HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists. AB - Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-of-knowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing. PMID- 27672289 TI - Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases. AB - Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis associated colon adenocarcinomas. Recent results demonstrated that endogenous c MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be selected for combined regiments. However, due to its context-dependent cellular function, it is clinically essential to consider which cytotoxic drugs are used in combination with c-MYC targeted agents in various tissues. Increasing our knowledge about MYC-dependent pathways might provide direction to novel anti-inflammatory and colorectal cancer therapies. PMID- 27672291 TI - Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions? AB - Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association. PMID- 27672290 TI - Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. AB - Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity. PMID- 27672292 TI - Portal biliopathy. AB - Portal biliopathy refers to cholangiographic abnormalities which occur in patients with portal cavernoma. These changes occur as a result of pressure on bile ducts from bridging tortuous paracholedochal, epicholedochal and cholecystic veins. Bile duct ischemia may occur due prolonged venous pressure effect or result from insufficient blood supply. In addition, encasement of ducts may occur due fibrotic cavernoma. Majority of patients are asymptomatic. Portal biliopathy is a progressive disease and patients who have long standing disease and more severe bile duct abnormalities present with recurrent episodes of biliary pain, cholangitis and cholestasis. Serum chemistry, ultrasound with color Doppler imaging, magnetic resonance imaging with magnetic resonance cholangiopancreatography and magnetic resonance portovenography are modalities of choice for evaluation of portal biliopathy. Endoscopic retrograde cholangiography being an invasive procedure is indicated for endotherapy only. Management of portal biliopathy is done in a stepwise manner. First, endotherapy is done for dilation of biliary strictures, placement of biliary stents to facilitate drainage and removal of bile duct calculi. Next portal venous pressure is reduced by formation of surgical porto-systemic shunt or transjugular intrahepatic portosystemic shunt. This causes significant resolution of biliary changes. Patients who persist with biliary symptoms and bile duct changes may benefit from surgical biliary drainage procedures (hepaticojejunostomy or choledechoduodenostomy). PMID- 27672293 TI - Transanal surgery for obstructed defecation syndrome: Literature review and a single-center experience. AB - Obstructed defecation syndrome (ODS) is a functional disorder commonly encountered by colorectal surgeons and gastroenterologists, and greatly affects the quality of life of patients from both societal and psychological aspects. The underlying anatomical and pathophysiological changes of ODS are complex. However, intra-rectal intussusception and rectocele are frequently found in patients with ODS and both are thought to play an important role in the pathogenesis of ODS. With the development of evaluation methods in anorectal physiology laboratories and radiology studies, a great variety of new operative procedures, especially transanal procedures, have been invented to treat ODS. However, no procedure has been proved to be superior to others at present. Each operation has its own merits and defects. Thus, choosing appropriate transanal surgical procedures for the treatment of ODS remains a challenge for all surgeons. This review provides an introduction of the current problems and options for treatment of ODS and a detailed summary of the essential assessments needed for patient evaluation before carrying out transanal surgery. Besides, an overview of the benefits and problems of current transanal surgical procedures for treatment of ODS is summarized in this review. A report of clinical experience of some transanal surgical techniques used in the authors' center is also presented. PMID- 27672294 TI - Oncolytic viruses against cancer stem cells: A promising approach for gastrointestinal cancer. AB - Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell (CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer (liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations. PMID- 27672295 TI - Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature. AB - The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus (HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen (HBsAg) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBsAg-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBsAg positive grafts have preferentially been allocated to HBsAg positive recipients. The large majority of these patients continue to be HBsAg positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBsAg negative recipients, although they are mostly promising. HBsAg-positive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented. PMID- 27672296 TI - May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis? AB - AIM: To evaluate mucosal baseline mRNA expression of tissue transglutaminase 2 (tTG2), interferon gamma (IFNgamma), toll-like receptor 2 (TLR2) and Myeloid Differentiation factor 88 (MyD88) in patients with microscopic enteritis (ME). METHODS: We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count (IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction (RT-PCR) was used to detect the amount of mRNA coding for tTG2, IFNgamma, TLR2 and MyD88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance (ANOVA) and Bonferroni's test. The chi(2) test was used for categorical variables. Pearson's test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and GS. RESULTS: After a period of follow up of 21.7 +/- 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects (31 CD; 17 GS) and non-gluten related ones in 41 (29 Irritable Bowel Syndrome - IBS; 12 Others). CD patients had the highest tTG2 levels (8.3 +/- 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNgamma levels (8.5 +/- 4.1). ANOVA plus Bonferroni demonstrated CD > Other ME > GS = IBS > negative controls. A cut off of 1.853 was able to differentiate CD and GS with a sensitivity of 47.06% and a specificity of 96.77%. Patients with non gluten-related causes of ME exhibited the highest TLR2 levels (6.1 +/- 1.9) as follows: Other ME > CD = GS = IBS > negative controls. TLR2 was unable to discriminate CD from GS. Patients with CD overexpressed MyD88 levels similarly to non gluten-related causes of DL (7.8 +/- 4.9 and 6.7 +/- 2.9), thus CD = Other ME > GS = IBS > negative controls. A cut off of 3.722 was able to differentiate CD from GS with a sensitivity of 52.94% and a specificity of 74.19%. IELs count (15-25 and more than 25/100 enterocytes) strongly correlated with mRNA levels of all tested molecules (P < 0.0001). CONCLUSION: Our results confirm that a single marker is unable to predict a discrimination among ME underlying conditions as well as between CD and GS. Mucosal high levels of tTG and IFNgamma mRNA may predict the development of CD more than GS with high specificity, despite an expected low sensitivity. TLR2 does not discriminate the development of CD from GS. MyD88 levels indicate that intestinal permeability is more increased when a severe intestinal damage underlies ME in both gluten related and unrelated conditions. Therefore, the results of the present paper do not seem to show a clear translational value. PMID- 27672297 TI - Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease. AB - AIM: To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS: Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS: Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, alpha-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE(-/ ) animals developed NASH of similar severity to RAGE(+/+) animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION: In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID- 27672298 TI - Different pre-S deletion patterns and their association with hepatitis B virus genotypes. AB - AIM: To investigate the associations of different types of pre-S deletions with hepatitis B virus (HBV) genotypes. METHODS: The sequences of the pre-S region, basal core promoter (BCP) mutation, and precore (PC) mutation were examined through direct DNA sequencing or clonal analysis and sequencing in 273 HBV carriers, namely 55 asymptomatic carriers, 55 carriers with chronic hepatitis (CH), 55 with liver cirrhosis (LC), 53 with liver cirrhotic hepatocellular carcinoma (LC-HCC), and 55 with noncirrhotic HCC. A total of 126 HBV carriers (46.2%) harbored pre-S deletions. The DNA sequences of pre-S deletion mutants from 43 age-matched genotype B (HBV/B)-infected carriers and 43 age-matched genotype C (HBV/C)-infected carriers were further examined, aligned, and compared. RESULTS: No significant difference was observed in the mean age distribution (P = 0.464), male sex (P = 0.805), viral load (P = 0.635), or BCP mutation (P = 0.117) between the HBV/B and HBV/C groups. However, the rate of PC mutation was significantly higher in the HBV/B-infected carriers than in the HBV/C-infected carriers (P = 0.003). Both genotypes exhibited a high rate of deletion in the C-terminal half of the pre-S1 region and N-terminus of the pre-S2 region (86.0% and 79.1% in the HBV/B group; 69.8% and 72.1% in the HBV/C group, respectively). Epitope mapping showed that deletion in several epitope sites was frequent in both genotypes, particularly pS1-BT and pS2-B2. Conversely, the rate of pS2-B1 deletion was significantly higher in the HBV/B group (72.1% vs 37.2%, P = 0.002), and the rate of pS2-T deletion was significantly higher in the HBV/C group (48.8% vs 25.6%, P = 0.044). Functional mapping showed that the rate of deletion in three functional sites (the nucleocapsid binding site, start codon of M, and site for viral secretion) located in the N-terminus of the pre-S2 region was significantly higher in the HBV/B group (P < 0.05). One type of N-terminus pre-S1 deletion mutant with deletion of the start codon of the L protein was frequently observed in the HBV/C group (20.9% vs 9.3%, P = 0.228), particularly in the LC patients (42.9% vs 12.5%). Different patterns of pre-S deletions were also found between the HBV/B and HBV/C groups according to different clinical outcomes. In CH patients, deletion in the site for polymerized human serum albumin was more frequent in the HBV/B group (88.9% vs 36.4%, P = 0.028). In the LC-HCC patients, the rate of deletion in the pre-S2 region was significantly higher in the HBV/B group than in the HBV/C group (P < 0.05). CONCLUSION: HBV/B- and HBV/C-infected carriers exhibit different patterns of pre-S deletion, which may be associated with the progression of liver diseases. PMID- 27672299 TI - Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12. AB - AIM: To gather data on the antiviral efficacy and safety of second generation direct acting antiviral (DAA) treatment with respect to sustained virological response (SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting. METHODS: Two hundred and sixty patients treated with SOF combination partners PR (n = 51), R (n = 10), SMV (n = 30), DCV (n = 81), LDV (n = 73), or 3D (n = 15). 144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score >= 10 and 17/260 were post-liver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3. RESULTS: Two hundred and forty/256 (93.7%) patients achieved SVR12 (mITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/nL, 88% post-liver transplantation, 95% for GT1a, 93% for GT1b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score >= 10 (P < 0.0001), liver cirrhosis (P = 0.005) at baseline. In Interferon-free treatment GT3 had significantly lower SVR rates than GT1 (P = 0.016). Side effects were mild. CONCLUSION: Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into "real-world". Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/nL and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure. PMID- 27672301 TI - Reflective Journaling as a Flipped Classroom Technique to Increase Reading and Participation With Social Work Students. AB - Students in undergraduate social work practice courses come to the class with varying levels of educational, life, and practice experience. Students require an introduction to the material through textbook reading before they are able to engage in critical discussions, yet reading adherence varies widely among students. This research explores the use of reflective journals as a Flipped Classroom technique to increase reflective thinking and reading adherence. This study surveys 27 students in two practice courses about the use of weekly reflective journaling as a flipped classroom assignment. Findings support that reflective reading journals increase student preparation and engagement, but require more work for students and instructors. Implications are discussed. PMID- 27672300 TI - Trajectories of endoscopic Barrett esophagus: Chronological changes in a community-based cohort. AB - AIM: To elucidate longitudinal changes of an endoscopic Barrett esophagus (BE), especially of short segment endoscopic BE (SSBE). METHODS: This study comprised 779 patients who underwent two or more endoscopies between January 2009 and December 2015. The intervals between the first and the last endoscopy were at least 6 mo. The diagnosis of endoscopic BE was based on the criteria proposed by the Japan Esophageal Society and was classified as long segment (LSBE) and SSBE, the latter being further divided into partial and circumferential types. The potential background factors that were deemed to affect BE change included age, gender, antacid therapy use, gastroesophageal reflux disease-suggested symptoms, esophagitis, and hiatus hernia. Time trends of a new appearance and complete regression were investigated by Kaplan-Meier curves. The factors that may affect appearance and complete regression were investigated by chi(2) and Student-t tests, and multivariable Cox regression analysis. RESULTS: Incidences of SSBE and LSBE were respectively 21.7% and 0%, with a mean age of 68 years. Complete regression of SSBE was observed in 61.5% of initial SSBE patients, while 12.1% of initially disease free patients experienced an appearance of SSBE. Complete regressions and appearances of BE occurred constantly over time, accounting for 80% and 17% of 5-year cumulative rates. No LSBE development from SSBE was observed. A hiatus hernia was the only significant factor that facilitated BE development (P = 0.03) or hampered (P = 0.007) BE regression. CONCLUSION: Both appearances and complete regressions of SSBE occurred over time. A hiatus hernia was the only significant factor affecting the BE story. PMID- 27672302 TI - An Integrative Theory of Psychotherapy: Research and Practice. AB - A dual-process personality theory and supporting research are presented. The dual processes comprise an experiential system and a rational system. The experiential system is an adaptive, associative learning system that humans share with other higher-order animals. The rational system is a uniquely human, primarily verbal, reasoning system. It is assumed that when humans developed language they did not abandon their previous ways of adapting, they simply added language to their experiential system. The two systems are assumed to operate in parallel and are bi-directionally interactive. The validity of these assumptions is supported by extensive research. Of particular relevance for psychotherapy, the experiential system, which is compatible with evolutionary theory, replaces the Freudian maladaptive unconscious system that is indefensible from an evolutionary perspective, as sub-human animals would then have only a single system that is maladaptive. The aim of psychotherapy is to produce constructive changes in the experiential system. Changes in the rational system are useful only to the extent that they contribute to constructive changes in the experiential system. PMID- 27672303 TI - Prevalence of Chlamydia trachomatis among Childbearing Age Women in India: A Systematic Review. AB - Background. Infection with Chlamydia trachomatis (CT) can lead to reproductive sequelae. Information on the general population of childbearing age women in India is sparse. We reviewed the literature on CT prevalence within the general population of reproductive aged women in order to improve the efforts of public health screening programs and interventions. Objective. To conduct a literature review to determine the prevalence of Chlamydia trachomatis among childbearing age women in India. Search Strategy. Ovid Medline and PubMed databases were searched for articles from January 1, 2003, through December 31, 2014. Search terms included "Chlamydia trachomatis", "CT", "prevalence", "India", and "sexually transmitted infections". Selection Criteria. Studies on prevalence data for CT among women of childbearing age (15-45) living in India were included. Data Collection and Analysis. Articles that met the inclusion criteria were extracted by two readers and discrepancies solved through discussion. Results. Reported prevalence of active CT infection among lower risk groups ranged from 0.1% to 1.1% and in higher risk group from 2.7% to 28.5%. Conclusion. CT prevalence among women in India is comparable to other countries. Screening programs to prevent adverse outcomes among Indian women of childbearing age and their offspring are warranted. PMID- 27672305 TI - Successful conjunctival socket expansion in anophthalmic patients until the age of 2 years: an outpatient procedure. AB - PURPOSE: To report the results of a simple outpatient method for soft tissue socket expansion in young children with congenital anophthalmos. METHODS: Seventeen congenital anophthalmic sockets of 15 infants of a mean age of 4.2+/ 4.4 months were fitted with specially designed serial solid acrylic shapes or hydrogel expanders using cyanoacrylate for eyelids closure when using the latter. RESULTS: At the age of 2 years, the mean horizontal eyelid length increased from a mean of 11.6+/-4.5 to 19.4+/-4.6 mm and the volume of the last expander from a mean of 0.6+/-0.2 to 2.0+/-0.3 cm(2). The specially designed acrylic shapes could be a substitute to the custom-made molds, which require general anesthesia. CONCLUSION: Successful increase in the horizontal eyelid length as well as the conjunctival socket volume could be achieved by a simple outpatient procedure without the need for repeated hospitalization and general anesthesia in these infants. PMID- 27672304 TI - Optic nerve head topography and retinal structural changes in eyes with macrodisks: a comparative study with spectral domain optical coherence tomography. AB - PURPOSE: To compare optic nerve head parameters, the thicknesses of the peripapillary retinal nerve fiber layer (pRNFL), the macular retinal nerve fiber layer (mRNFL), the ganglion cell complex (GCC), and the ganglion cell-inner plexiform layer (GCIPL) in macrodisks and normal-sized healthy disks using spectral domain optical coherence tomography. PATIENTS AND METHODS: A total of 88 healthy eyes (42 macrodisks and 46 normal-sized disks) were prospectively enrolled in the study. Optic nerve head parameters as well as pRNFL, mRNFL, GCC, and GCIPL thicknesses were measured in all subjects. Optic disk areas (ODAs) >2.70 mm(2) were defined as macrodisks. All spectral domain optical coherence tomography parameters were compared between normal-sized disks and macrodisks. RESULTS: The mean age of the participants was 49.4+/-5.7 years in the normal size group and 51.55+/-6.3 years in the macrodisk group (P=0.65). The average ODAs were 2.23+/-0.29 mm(2) and 3.30+/-0.59 mm(2) in the normal size and the macrodisk groups, respectively. ODA (P<0.001), cup area (P<0.001), cup disk area ratio (P<0.001), horizontal cup disk ratio (P<0.001), vertical cup disk ratio (P<0.001), horizontal disk diameter (P<0.001), vertical disk diameter (P<0.001), and cup volume (P<0.001) were significantly higher in the macrodisk group. The inferior mRNFL thickness was significantly lower (P=0.042), and the GCC inferior and GCIPL inferior thicknesses were found to be lower with low significance (P=0.052, P=0.059, respectively) in the macrodisk group. Rim volume (P=0.622), total pRNFL (P=0.201), superior pRNFL (P=0.123), inferior pRNFL (P=0.168), average macular thickness (P=0.162), total mRNFL (P=0.171), superior mRNFL (P=0.356), total GCC (P=0.080), superior GCC (P=0.261), total GCIPL (P=0.214), and superior GCIPL (P=0.515) thicknesses were similar in both groups. CONCLUSION: Optic disk topography and retinal structures show different characteristics in healthy eyes with macrodisks. These disk size-dependent variations suggest that large optic disks may be more susceptible to glaucomatous damage. PMID- 27672306 TI - Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians. AB - PURPOSE: To investigate myopic choroidal neovascularization (mCNV) by fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), near infrared (NIR) reflectance, and autofluorescence (AF). METHODS: This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63-70 years) and a mean refraction of 9.72 diopters (95% CI -8.74 to -10.70 diopters). RESULTS: Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%), with thickening of the corresponding retina (62/65, 95.3%) and leakage on FA (44/65, 67.6%). No retinal fluid was detectable in 32 (49.2%) eyes and there was no hemorrhage in 25 (38.4%) eyes. Papillary chorioretinal atrophy was evident in 58 (89.2%), a shadowing effect in 48 (73.8%), and an epiretinal membrane in 38 (58.4%) eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P?0.001). In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P?0.005). NIR and AF features were indeterminable in 19 (29.2%) and 27 (41.5%) eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3%) and patchy (hypo- and hyperfluorescence was observed) on AF (25/65, 38.4%). FA and SD-OCT correctly detected mCNV in 49 (75.3%) and 48 (73.8%) eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P?0.001), absence of retinal fluid and epiretinal membrane (P?0.05), and presence of macular chorioretinal atrophy (P?0.01). CONCLUSION: Tomographic, angiographic, AF, and NIR features of mCNV are described in this study. Combination of SD-OCT and FA is recommendable for diagnosis. PMID- 27672307 TI - Preservative-free bimatoprost 0.03% in patients with primary open-angle glaucoma or ocular hypertension in clinical practice. AB - BACKGROUND: Intraocular pressure (IOP)-lowering medications for primary open angle glaucoma and ocular hypertension commonly contain preservatives that can cause ocular surface damage in many patients. The purpose of this study was to evaluate the efficacy and tolerability of, and compliance to, preservative-free (PF) bimatoprost 0.03% in patients with primary open-angle glaucoma or ocular hypertension (IOP >=18 mmHg) in a clinical practice setting. METHODS: This open label study observed patients who were switched to PF bimatoprost 0.03% for medical reasons. IOP was measured at baseline and ~12 weeks later at the final visit, and the change in IOP was calculated. Tolerability and continuation of therapy were assessed at two follow-up visits. RESULTS: A total of 1,830 patients were included in the study, and complete IOP data were available for 1,543 patients. Mean IOP was reduced by 23% from 21.64 mmHg to 16.59 mmHg (P<0.0001). In subgroup analyses, the mean IOP was significantly reduced compared with baseline, regardless of prior therapy, including those previously treated with PF monotherapy. A total of 85.7% of physicians reported the IOP-lowering efficacy of PF bimatoprost 0.03% to be as expected or better than expected. Adverse events (AEs) were experienced by 5.7% of patients, and there were no serious AEs reported. The most common AEs were eye irritation (1.7%) and hyperemia (1.4%). Physician-reported treatment compliance was reported as better than (48.7%) or equal to (43.6%) prior treatment in most patients. Most patients (82%) were expected to continue PF bimatoprost 0.03% after the end of the study. CONCLUSION: This observational study showed that, in clinical practice, switching to PF bimatoprost 0.03% was associated with a significant IOP reduction from baseline. There was a low AE rate. PF bimatoprost 0.03% may, therefore, be an effective treatment option for patients who are intolerant of preservatives or have an inadequate response to prior IOP-lowering treatments. PMID- 27672309 TI - Efficacy and safety of monoclonal antibodies targeting interleukin-17 pathway for inflammatory arthritis: a meta-analysis of randomized controlled clinical trials. AB - T-helper 17 (Th17) pathway plays an important and distinct role in autoimmunity and inflammation. A growing body of evidence demonstrates that interleukin-17 (IL 17) is also synthesized in inflammatory arthritis tissues and exerts potent proinflammatory and joint-destructive activities. Clinical studies have been performed to evaluate the therapeutic efficacy of antibodies blocking the IL-17 signaling pathway in patients with rheumatoid arthritis (RA). In this study, we performed a meta-analysis to systematically evaluate the clinical effects of IL 17 antibodies in RA patients. By searching PubMed, five randomized, placebo controlled randomized controlled clinical trials that tested three antibodies against IL-17A (LY2439821 and secukinumab/AIN457) and the IL-17A receptor (brodalumab) were identified. The primary outcomes that were analyzed include American College of Rheumatology (ACR) Improvement Criteria and Disease Activity Score in 28 joints (DAS28). Meanwhile, the safety and adverse effects were also systematically analyzed. The results of the meta-analysis demonstrated that IL-17 antibody is effective in ameliorating the RA symptoms. Specifically, IL-17 blocking antibody significantly reduced ACR20 and ACR50. It also dramatically reduced DAS28, an index that measures tenderness and swelling severity of joints. The side effects of and intolerance to the antibody treatment were higher than those in the placebo control. The analysis result provides evidence-based information for clinical use of these agents in the treatment of inflammatory arthritis. PMID- 27672310 TI - Synthesis, solubility, plasma stability, and pharmacological evaluation of novel sulfonylhydrazones designed as anti-diabetic agents. AB - Neuropathy is a serious complication of diabetes that has a significant socioeconomic impact, since it frequently demands high levels of health care consumption and compromises labor productivity. Recently, LASSBio-1471 (3) was demonstrated to improve oral glucose tolerance, reduce blood glucose levels, and display an anti-neuropathy effect in a murine streptozotocin-induced diabetes model. In the present work, we describe the design, synthesis, solubility, plasma stability, and pharmacological evaluation of novel sulfonylhydrazone derivatives (referred to herein as compounds 4-9), which were designed by molecular modification based on the structure of the prototype LASSBio-1471 (3). Among the compounds tested, better plasma stability was observed with 4, 5, and 9 in comparison to compounds 6, 7, and 8. LASSBio-1773 (7), promoted not only hypoglycemic activity but also the reduction of thermal hyperalgesia and mechanical allodynia in a murine model of streptozotocin-induced diabetic neuropathic pain. PMID- 27672308 TI - Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis. AB - Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit-risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the alpha subunit of the high-affinity interleukin 2 (IL 2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56(bright) natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID- 27672311 TI - Understanding cytoskeleton regulators in glioblastoma multiforme for therapy design. AB - The cellular cytoskeleton forms the primary basis through which a cell governs the changes in size, shape, migration, proliferation, and forms the primary means through which the cells respond to their environment. Indeed, cell and tissue morphologies are used routinely not only to grade tumors but also in various high content screening methods with an aim to identify new small molecules with therapeutic potential. This study examines the expression of various cytoskeleton regulators in glioblastoma multiforme (GBM). GBM is a very aggressive disease with a low life expectancy even after chemo- and radiotherapy. Cancer cells of GBM are notorious for their invasiveness, ability to develop resistance to chemo- and radiotherapy, and to form secondary site tumors. This study aims to gain insight into cytoskeleton regulators in GBM cells and to understand the effect of various oncology drugs, including temozolomide, on cytoskeleton regulators. We compare the expression of various cytoskeleton regulators in GBM-derived tumor and normal tissue, CD133-postive and -negative cells from GBM and neural cells, and GBM stem-like and differentiated cells. In addition, the correlation between the expression of cytoskeleton regulators with the clinical outcome was examined to identify genes associated with longer patient survival. This was followed by a small molecule screening with US Food and Drug Administration (FDA)-approved oncology drugs, and its effect on cellular cytoskeleton was compared to treatment with temozolomide. This study identifies various groups of cytoskeletal regulators that have an important effect on patient survival and tumor development. Importantly, this work highlights the advantage of using cytoskeleton regulators as biomarkers for assessing prognosis and treatment design for GBM. PMID- 27672313 TI - Comparison of pharmacist and public views and experiences of community pharmacy medicines-related services in England. AB - BACKGROUND: Services provided by community pharmacists designed to support people using medicines are increasing. In England, two national services exist: Medicine Use Reviews (MUR) and New Medicines Service (NMS). Very few studies have been conducted seeking views of the public, rather than service users, on willingness to use these services or expectations of these services, or determined whether views align with pharmacist perceptions. OBJECTIVE: To compare the perceptions of pharmacists and the general public on medicines-related services, particularly MUR and NMS services. METHODS: Two parallel surveys were conducted in one area of England: one involved the general public and was administered using a street survey, and the other was a postal survey of community pharmacists. Similar questionnaires were used, seeking views of services, awareness, reasons for using services, and perceived benefits. RESULTS: Response rates were 47.2% (1,000/2,012 approached) for the public and 40.8% (341/836) for pharmacists. Few people had experienced a discussion in a private consultation room or were aware of the two formal services, although their willingness to use them was high. Pharmacists estimated time spent on service provision as 10 minutes for MUR and 12 minutes for NMS, which aligned with acceptability to both pharmacists and the public. Pharmacists underestimated the willingness of the public to wait for an informal discussion or to make appointments for formal services. Both pharmacists and the public had high expectations that services would be beneficial in terms of increasing knowledge and understanding, but public expectations and experiences of services helping to sort out problems fell well below pharmacists' perceptions. People who had experienced a pharmacy service had different perceptions of pharmacists. CONCLUSION: Views differed regarding why people use services and key aspects of service delivery. For services to improve, the pharmacy profession needs a better awareness of what the public, especially those with potential to benefit from services, view as acceptable and desirable. PMID- 27672312 TI - Effects of an immunosuppressive treatment on the rat prostate. AB - The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins. PMID- 27672314 TI - Psychometric properties of the Polish version of the eight-item Morisky Medication Adherence Scale in hypertensive adults. AB - Low adherence to pharmacological treatment is often associated with poor blood pressure control, but identification of nonadherent patients in outpatient settings is difficult. The aim of the study was to translate and evaluate the psychometric properties of the Polish version of the structured self-report eight item Morisky Medication Adherence Scale (MMAS-8) among patients with hypertension. The study was conducted in a family doctor practice between January and July 2015. After a standard "forward-backward" procedure to translate MMAS-8 into Polish, the questionnaire was administered to 160 patients with hypertension. Reliability was tested using a measure of internal consistency (Cronbach's alpha) and test-retest reliability. Validity was confirmed using known group validity. Three levels of adherence were considered based on the following scores: 0 to <6 (low); 6 to <8 (medium); and 8 (high). Complete questionnaires were returned by 110 respondents (mean age: 60.7 years +/-12.6; 54.6% were female). The mean number of pills taken daily was 3.61+/-4.31. The mean adherence score was 6.42+/- 2.0. Moderate internal consistency was found (Cronbach's alpha=0.81), and test-retest reliability was satisfactory (r=0.461 0.905; P<0.001). Reproducibility expressed by Cohen's kappa coefficient =0.61 was good. In high-adherent patients, the percentage of well-controlled blood pressure was higher than in low-adherent patients (33.3% vs 19.1%, chi (2)=0.87, P=0.648). Psychometric evaluation of the Polish version of the MMAS-8 indicates that it is a reliable and valid measure tool to detect nonadherent patients. The MMAS-8 may be routinely used to support communication about the medication-taking behavior in hypertensive patients. PMID- 27672315 TI - Atypical antipsychotics as add-on treatment in late-life depression. AB - BACKGROUND: Second-generation antipsychotics (SGAs) have been used in the augmentation of treatment-resistant depression. However, little is known about their effectiveness, tolerability, and adverse events in the treatment of late life depression, which were the aim of this study. METHODS: The retrospective data of patients aged >65 years who had a major depressive episode with inadequate response to antidepressant treatment and had adjuvant SGA treatment were analyzed. The outcome measures were the number of the patients who continued to use SGAs in the fourth and twelfth weeks, adverse events, and changes in symptoms of depression. RESULTS: Thirty-five patients were screened: 21 (60%) had quetiapine, twelve (34.28%) had aripiprazole, and two (5.71%) had olanzapine adjuvant treatment. The mean age was 72.17+/-5.02 years, and 65.7% of the patients were women. The mean daily dose was 85.71+/-47.80 mg for quetiapine, 3.33+/-1.23 mg for aripiprazole, and 3.75+/-1.76 mg for olanzapine. The Geriatric Depression Scale scores of all patients were significantly decreased in the fourth week and were significant in the aripiprazole group (P=0.02). Of the 35 patients, 23 (65.7%) patients discontinued the study within 12 weeks. The frequency of adverse events was similar in all SGAs, and the most common were sedation, dizziness, constipation, and orthostatic hypotension with quetiapine, and akathisia and headache because of aripiprazole. CONCLUSION: This study indicates that dropout ratio of patients with SGAs is high, and a subgroup of patients with late-life depression may benefit from SGAs. Effectiveness is significant in aripiprazole, and adverse events of SGAs were not serious but common in elderly patients. PMID- 27672316 TI - Pseudophakic cystoid macular edema: update 2016. AB - Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice. PMID- 27672317 TI - Use of the Internet as a prevention tool against cognitive decline in normal aging. AB - Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. PMID- 27672318 TI - Nutritional intervention in cognitively impaired geriatric trauma patients: a feasibility study. AB - BACKGROUND: Most studies focusing on improving the nutritional status of geriatric trauma patients exclude patients with cognitive impairment. These patients are especially at risk of malnutrition at admission and of worsening during the perioperative fasting period. This study was planned as a feasibility study to identify the difficulties involved in including this high-risk collective of cognitively impaired geriatric trauma patients. PATIENTS AND METHODS: This prospective intervention study included cognitively impaired geriatric patients (Mini-Mental State Examination <25, age >65 years) with hip related fractures. We assessed Mini Nutritional Assessment (MNA), Nutritional Risk Screening (NRS 2002), body mass index, calf circumference, American Society of Anesthesiologists' classification, and Braden Scale. All patients received parenteral nutritional supplementation of 800 kcal/d for the 96-hour perioperative period. Serum albumin and pseudocholinesterase were monitored. Information related to the study design and any complications in the clinical course were documented. RESULTS: A total of 96 patients were screened, among whom eleven women (median age: 87 years; age range: 74-91 years) and nine men (median age: 82 years; age range: 73-89 years) were included. The Mini-Mental State Examination score was 9.5 (0-24). All patients were manifestly undernourished or at risk according to MNA and NRS 2002. The body mass index was 23 kg/m2 (13-30 kg/m2), the calf circumference was 29.5 cm (18-34 cm), and the mean American Society of Anesthesiologists' classification status was 3 (2-4). Braden Scale showed 18 patients at high risk of developing pressure ulcers. In all, 12 patients had nonsurgical complications with 10% mortality. Albumin as well as pseudocholinesterase dropped significantly from admission to discharge. The study design proved to be feasible. CONCLUSION: The testing of MNA and NRS 2002 was feasible. Cognitively impaired trauma patients proved to be especially at risk of malnutrition. Since 96 hours of parenteral nutrition as a crisis intervention was insufficient, additional supplementation could be considered. Laboratory and functional outcome parameters for measuring successive supplementation certainly need further evaluations involving randomized controlled trials. PMID- 27672319 TI - Effect-site concentration of remifentanil for preventing cough during emergence in elderly patients undergoing nasal surgery: a comparison with adult patients. AB - PURPOSE: Prevention of cough during emergence after nasal surgery is important for avoiding surgical site bleeding. We investigated the remifentanil effect-site concentration in 50% (EC50) of the elderly patients undergoing nasal surgery for smooth emergence without cough and compared it with that of adult patients. METHODS: Twenty-two elderly (aged 65-80 years) and 25 adult patients (aged 20-60 years) with an American Society of Anesthesiologists physical status I/II undergoing nasal surgery were enrolled. Anesthesia was maintained with sevoflurane and remifentanil. Remifentanil EC50 and EC95 for preventing cough were determined using the modified Dixon's up-and-down method and isotonic regression with bootstrapping approach. Recovery profiles were also recorded. RESULTS: With Dixon's up-and-down method, the EC50 of remifentanil in elderly patients (2.40+/-0.25 ng/mL) was not significantly different from that of adults (2.33+/-0.30 ng/mL) (P=0.687). With isotonic regression, the EC95 of remifentanil in elderly patients (3.32 [95% confidence interval: 3.06-3.38] ng/mL) was not significantly different from that of adults (3.30 [95% confidence interval: 2.96 3.37] ng/mL). However, eye opening time (14.1+/-3.8 vs 12.0+/-2.9 seconds), extubation time (17.2+/-4.1 vs 14.0+/-3.0 seconds), and postanesthesia care unit duration (44.5+/-7.6 vs 38.7+/-3.4 minutes) in elderly patients were significantly longer than those in adults (P<0.05). CONCLUSION: Remifentanil EC50 for preventing cough after nasal surgery with sevoflurane anesthesia did not differ between elderly and adult patients. However, delayed awakening and respiratory adverse events may warrant attention in elderly patients. PMID- 27672320 TI - The association of renin-angiotensin system blockades and pneumonia requiring admission in patients with COPD. AB - BACKGROUND: The hallmark of COPD is chronic airway inflammation, which may be mediated by renin-angiotensin system. The renin-angiotensin system blockers such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) have exhibited anti-inflammatory and immunomodulatory effects in patients with various diseases. We explored the effects of ACEi and ARBs on the risk of pneumonia in patients with COPD. METHODS: A nested case-control study was performed on COPD patients recruited from January 2010 to August 2013 in two referral hospitals in Korea. A total of 130 COPD patients admitted with pneumonia were included, and 245 COPD patients without pneumonia were selected as controls from a total of 1,646 such patients. Controls were matched with test patients by age, sex, and severity of airflow limitation. The effects of ACEi/ARBs use on the odds ratio (OR) for the development of pneumonia were tested through conditional logistic regression. RESULTS: Elderly patients (over 70 years of age) constituted ~30% of each group; most of the patients were male (85%). Of the COPD patients with pneumonia, 21.5% had taken ACEi/ARBs for a mean of 9.8 months (standard deviation +/-3.5 months). The proportions of ACEi/ARBs users and the mean duration of such use did not differ when compared to those of the control patients (26.9%, P=0.25; 9.6+/-3.6 months, P=0.83). Univariate analyses indicated that the use of ACEi/ARBs was not associated with a decreased risk of pneumonia (OR =0.70, 95% confidence interval 0.41-1.23, P=0.21), whereas both a history of pulmonary tuberculosis (OR =1.85, 95% confidence interval 1.12-3.06, P=0.02) and exposure to systemic steroids (OR =2.33, 95% confidence interval 1.28-4.23, P=0.005) did show an association. After adjustment for a history of tuberculosis, comorbid chronic renal disease, and exposure to corticosteroids, ACEi/ARBs reduced the risk of pneumonia in COPD patients (OR =0.51, 95% confidence interval 0.27-0.98, P=0.04). CONCLUSION: This study revealed that the use of ACEi/ARBs was associated with reducing the risk of pneumonia in patients with COPD. Further prospective studies are necessary to confirm the protective effect of ACEi/ARBs and elucidate the underlying mechanisms in COPD patients. PMID- 27672321 TI - Lost in interpretation: should the highest VC value be used to calculate the FEV1/VC ratio? PMID- 27672322 TI - Scabies increased the risk and severity of COPD: a nationwide population-based study. AB - BACKGROUND: Scabies is a common parasitic infectious disease, and COPD is a major pulmonary disease. However, there have been no previous studies that have investigated the relationship between scabies and COPD. MATERIALS AND METHODS: This nationwide population-based study included a total of 3,568 patients with scabies as the study group and 14,255 patients as a control group. We followed up patients in both groups for a 5-year period to identify any new diagnoses of COPD. We then followed them up for an additional 2-year period to determine the severity of any newly diagnosed cases of COPD as indicated by acute respiratory events. Cox proportional hazard regression analyses were performed to calculate the hazard ratio (HR) of COPD during the 5-year follow-up period and COPD complication during the additional 2-year follow-up period. RESULTS: Of the 17,823 patients in the study, 2,765 (15.5%) were newly diagnosed with COPD during the 5-year follow-up period; 904 (32.7%) were from the scabies group; and 1,861 (67.3%) were from the control group. Compared to the patients without scabies, the adjusted HR (aHR) for COPD for the subjects with scabies was 1.72 (95% CI: 1.59-1.87) during the 5-year follow-up period. For those newly diagnosed with COPD, the aHR for COPD with acute exacerbation was 1.85 (95% CI: 1.67-2.06), the aHR for COPD with pneumonia was 3.29 (95% CI: 2.77-3.92), the aHR for COPD with acute respiratory failure was 4.00 (95% CI: 3.08-5.19), and the aHR for COPD with cardiopulmonary arrest was 3.95 (95% CI: 2.25-6.95) during the additional 2-year follow-up period. CONCLUSION: The results of this study indicate a 72% increased risk for COPD among patients with scabies. The results also reveal an increased risk of severe COPD complications such as acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation among patients with scabies. This useful information may help physicians in treating scabies and remaining alert to the potential development of COPD and its severe complications. PMID- 27672323 TI - The disease burden of chronic obstructive pulmonary disease in Greece. AB - BACKGROUND: The objective of the study was to estimate the self-reported prevalence of chronic obstructive pulmonary disease (COPD) in Greece and to quantify its burden on patients' daily activities, productivity, and psychological status. METHODS: A population-based, random digit-dialed telephone nationwide survey was conducted between July 10, 2015 and July 31, 2015 in order to recruit patients with COPD in Greece. Among the 11,471 persons contacted, 3,414 met the inclusion criterion of age >=40 years and completed the screening questions regarding COPD. Of the 362 subjects who reported that they had been diagnosed with COPD, 351 completed the survey. Data on demographic and lifestyle characteristics, comorbidities, disease history, perceived disease severity, breathlessness severity, symptoms severity, limitations in daily activities, psychological distress, and productivity were collected. All data were collected through the telephone interview method using a structured questionnaire. RESULTS: The overall self-reported COPD prevalence was 10.6%. Among 351 participants, only 9% reported that they suffered from severe breathlessness. The mean COPD assessment test score was 19.0, with 84% of participants having a COPD assessment test score >=10. As for the perceived severity of COPD, the majority of subjects considered that their respiratory condition was of moderate (34.2%) or mild severity (33.9%). Overall, the participants reported a significant impact of COPD on their daily life. For instance, 61.5% of them reported that their respiratory condition has affected their sports activities. Moreover, 73% of subjects considered that the health care system could do more for them than it actually does. Almost one-fourth of the participants reported that they had missed work during the past 12 months due to their respiratory symptoms, with the mean number of days lost being 10. CONCLUSION: This survey provides insightful data regarding the impact of COPD on Greek patients' everyday life, psychology, and productivity, revealing the increased individual morbidity and the significant burden of this condition on society. PMID- 27672324 TI - Alexithymia, impulsiveness, and psychopathology in nonsuicidal self-injured adolescents. AB - INTRODUCTION: Nonsuicidal self-injury (NSSI) is a multifaceted phenomenon and a major health issue among adolescents. A better understanding of self-injury comorbidities is crucial to improve our ability to assess, treat, and prevent NSSI. PURPOSE: This study aimed at analyzing some of the psychobehavioral correlates of NSSI: psychological problems, alexithymia, impulsiveness, and sociorelational aspects. PATIENTS AND METHODS: This was a case-control study. The clinical sample (n=33) included adolescents attending our unit for NSSI and other issues; the controls (n=79) were high-school students. Data were collected using six questionnaires: Youth Self-Report, Barratt's Impulsiveness Scale, Toronto Alexithymia Scale, Children's Depression Inventory, Symptom Checklist-90-R, and Child Behavior Checklist. RESULTS: Cases scored significantly higher in all questionnaires. Habitual self-injurers scored higher on impulsiveness and alexithymia. The gesture's repetition seems relevant to the global clinical picture: habitual self-injurers appear more likely to seek help from the sociosanitary services. We found a difference between the self-injurers' and their parents' awareness of the disorder. CONCLUSION: Habitual self-injurers show signs of having difficulty with assessing the consequences of their actions (nonplanning impulsiveness) and the inability to manage their feelings. Given the significantly higher scores found for cases than for controls on all the psychopathological scales, NSSI can be seen as a cross-category psychiatric disorder, supporting the Diagnostic and Statistical Manual of Mental Disorders decision to include it as a pathological entity in its own right. PMID- 27672325 TI - Autistic traits in women with primary dysmenorrhea: a case-control study. AB - OBJECTIVES: Recent studies have shown that women with autism spectrum disorder have higher rates of menstrual problems, including irregular menstrual cycles, unusually painful periods (dysmenorrhea), and excessive menstrual bleeding. In this study, we investigated the autistic traits in female university students with primary dysmenorrhea (PD). METHODS: Seventy females with PD and 70 females without PD were enrolled in the study. The Autism Spectrum Quotient (AQ) was used to measure autistic traits and the Brief Symptom Inventory was used for evaluating anxiety and depression levels. The dysmenorrheal pain was assessed by visual analog scale (VAS), coded from 0 to 10. Weight and height were measured, and the body mass index was calculated. RESULTS: There were no statistical differences between the groups in terms of age, duration of education, and body mass index. Women with PD had higher AQ - Total, and AQ - Attention Switching subscale scores than subjects without PD. Spearman analysis revealed that AQ - Total and AQ - Attention Switching scores were correlated with VAS. According to the linear regression analysis, VAS was predicted only by AQ - Attention Switching subscale. CONCLUSION: Our findings showed an association between autistic traits and dysmenorrhea in typically developing females. PMID- 27672326 TI - Reporting of adverse events related to dietary supplements to a public health center by medical staff: a survey of clinics and pharmacies. AB - BACKGROUND: Dietary supplements are used by >50% of the adult population in Japan, and adverse events related to these products have been reported with their increased use. Thus, an efficient system to gather and report data on these adverse events is essential. To date, however, reporting has been limited. The aim of this study was to address this deficiency by exploring the routine reporting practices of the medical staff employed at clinics or pharmacies in Japan. METHODS: We conducted a survey of the procedures used by the medical staff to report adverse events related to dietary supplement intake to public health centers in Japan. The survey was conducted in Japan between November 2015 and January 2016. Based on a sample size calculation, questionnaires were administered to 1,700 potential respondents (850 pharmacists and 850 physicians). The questionnaire inquired about the sociodemographic characteristics and dietary supplement-related adverse event-reporting practices. RESULTS: The response rate was 34.7%, including 286 pharmacists and 304 physicians. Although >30% of the pharmacists and physicians had prior experience dealing with such adverse events, <5% had reported these to a public health center. The survey identified several barriers to reporting, such as "difficulty judging the relationship between an adverse event and the dietary supplement" and "lack of clarity regarding the severity of an adverse event". CONCLUSION: This is the first study to explore the routine reporting practices of physicians and pharmacists in terms of adverse events related to dietary supplements. Further studies are required to elucidate the severity of these adverse events. Moreover, standard reporting criteria ought to be introduced to improve public health. PMID- 27672327 TI - Development of the parental needs scale for rare diseases: a tool for measuring the supportive care needs of parents caring for a child with a rare disease. AB - BACKGROUND: Children and families affected by rare diseases have received scant consideration from the medical, scientific, and political communities, with parents' needs especially having received little attention. Affected parents often have limited access to information and support and appropriate health care services. While scales to measure the needs of parents of children with chronic illnesses have been developed, there have been no previous attempts to develop a scale to assess the needs of parents of children with rare diseases. OBJECTIVE: To develop a scale for measuring the supportive care needs of parents of children with rare diseases. METHOD: A total of 301 responses to our Parental Needs Survey were randomly divided into two halves, one for exploratory factor analysis and the other for confirmatory factor analysis (CFA). After removing unsuitable items, exploratory factor analysis was undertaken to determine the factor structure of the data. CFA using structural equation modeling was then undertaken to confirm the factor structure. RESULTS: Seventy-two items were entered into the CFA, with a scree plot showing a likely four-factor solution. The results provided four independent subscales of parental needs: Understanding the disease (four items); Working with health professionals (four items); Emotional issues (three items); and Financial needs (three items). The structural equation modeling confirmed the suitability of the four-factor solution and demonstrated that the four subscales could be added to provide an overall scale of parental need. CONCLUSION: This is the first scale developed to measure the supportive care needs of parents of children with rare diseases. The scale is suitable for use in surveys to develop policy, in individual clinical assessments, and, potentially, for evaluating new programs. Measuring the supportive care needs of parents caring for a child with a rare disease will hopefully lead to better physical and psychological health outcomes for parents and their affected children. PMID- 27672328 TI - Proton therapy for early stage prostate cancer: is there a case? AB - Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT's future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery. PMID- 27672329 TI - Role of postmastectomy radiation therapy in breast cancer patients with T1-2 and 1-3 positive lymph nodes. AB - OBJECTIVE: To evaluate the role of radiotherapy (RT) in overall survival (OS) and disease-free survival in postmastectomy breast cancer patients with tumor size <5 cm, with 1-3 involved axillary lymph nodes (T1-2N1). PATIENTS AND METHODS: We conducted a retrospective study of 89 postmastectomy patients with T1-2N1 disease between 2005 and 2015 at the Radiation Oncology Clinic of Kayseri Training and Research Hospital. Clinicopathologic, demographic, and laboratory findings, as well as treatment regimens were investigated. OS and disease-free survival as well as factors that can be valuable in the prognosis were evaluated. RESULTS: A total of 89 female patients with an average age of 53 years (range: 30-81 years) were included in the assessment. Five-year and 10-year local recurrence rates were found to be 6.6% in the RT group and 7.1% in the non-RT group. In the RT group, the mean OS was 110.3 months and progression-free survival was 104.4 months. In the non-RT group, the corresponding figures were 104.3 months and 92.1 months, respectively. Statistically significant correlation was observed between RT and the American Joint Committee on Cancer stage (P<0.001), histological type (P=0.013), tumor size (P<0.001), and lymph node metastasis (P<0.001). During the assessment, locoregional recurrence and/or distant metastasis occurred in nine patients (10%). Locoregional recurrence was observed mostly in patients with invasive ductal carcinoma, tumor >3.0 cm in size, grade II tumors, and perinodal invasion, and who were premenopausal at the time of diagnosis. CONCLUSION: In T1 2N1 breast cancer patients who underwent modified radical mastectomy, when the effects of postmastectomy RT were evaluated, there were no differences in terms of OS and progression-free survival. In addition, when subgroup analysis was made, in patients with invasive ductal carcinoma, tumor diameter >2 cm, three lymph node metastasis, and stage 2b, postmastectomy RT was seen to be useful. PMID- 27672331 TI - Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node positive breast cancer patients. AB - PURPOSE: The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms. PATIENTS AND METHODS: Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor-node-metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model. RESULTS: Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47 years (range: 21-79 years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR =4.271; 95% CI 1.515-12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047-10.125; P=0.041). CONCLUSION: MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer. PMID- 27672330 TI - Correlation of PDK1 expression with clinicopathologic features and prognosis of hepatocellular carcinoma. AB - OBJECTIVE: To explore the clinical significance of 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in hepatocellular carcinoma (HCC) and its association with clinicopathologic features and prognosis in HCC patients. MATERIALS AND METHODS: A total of 128 HCC patients who received radical resection were enrolled from Wenling Maternal and Child Health Care Hospital between May 2005 and December 2008, and tumor and adjacent tissue samples were collected. Expression of PDK1 was detected by immunohistochemistry method. Correlation of PDK1 expression with clinicopathological features and prognosis was determined by Spearman's correlation analysis. Impact of expression of PDK1 on overall survival and recurrence was determined by Kaplan-Meier analysis. RESULTS: Immunohistochemistry results showed that PDK1 expression in HCC tissues was significantly higher than that in the corresponding adjacent cancer tissues. Univariate analysis showed that PDK1 messenger RNA expression can predict time to recurrence with diagnostic significance (P=0.001). Univariate analysis showed that alpha-fetoprotein level, tumor number, tumor encapsulation, microvascular invasion, and tumor-node-metastasis stage were also unfavorable prognostic variables for recurrence (P<0.05). Kaplan-Meier analysis showed that overexpression of PDK1 correlates with significantly shorter postoperative overall survival and higher recurrence rates (hazard ratio =2.68; 95% confidence interval: 2.46-4.42, P=0.001) in HCC patients after curative resection. CONCLUSION: Our study indicated that PDK1 may serve as a candidate pro-oncogene and a potential prognostic biomarker for HCC. PMID- 27672332 TI - Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms. AB - BACKGROUND/AIMS: Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. MATERIALS AND METHODS: Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor >=1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. RESULTS: A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766-6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003-1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067-1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173-0.990; P=0.047) was a preventive factor. CONCLUSION: The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis. PMID- 27672333 TI - Eribulin in the management of inoperable soft-tissue sarcoma: patient selection and survival. AB - Patients diagnosed with metastatic soft-tissue sarcoma (STS) have a poor prognosis. Additionally, after failure of first-line therapy, there are relatively few treatment options from which to choose. The novel tubulin-binding drug, eribulin, with a unique mechanism of action from taxanes or vinca alkaloids, has shown clinical activity in several different types of cancers. Eribulin has been approved by the US Food and Drug Administration (FDA) for patients with metastatic breast cancer previously treated with an anthracycline or a taxane and has recently been FDA approved for patients with unresectable or metastatic liposarcoma who have failed a previous anthracycline regimen. Here, we review current standard treatments of STS, a background of eribulin, the studies that have propelled eribulin to FDA approval for liposarcoma, and future directions of the drug. The benefits of eribulin in STS are discussed in detail, especially with regard to the recent pivotal Phase III study comparing eribulin to dacarbazine for leiomyosarcoma and adipocytic sarcoma. PMID- 27672335 TI - The association of PTEN hypermethylation and breast cancer: a meta-analysis. AB - OBJECTIVE: Phosphatase and tensin homolog (PTEN) deleted on chromosome 10, as a tumor suppressor gene, is crucial for the development of both familial and sporadic breast cancer (BC). The aim of this study was to perform a meta-analysis to evaluate the clinicopathological significance of PTEN promoter hypermethylation in BC. METHODS: A comprehensive literature search was made in PubMed, Embase, Google Scholar, Chinese database (China National Knowledge Infrastructure [CNKI]), and Web of Science. The analysis of pooled data was performed with Review Manager 5.2. The fixed-effects or random-effects models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The meta-analysis included eight studies and a total of 923 patients. The frequency of PTEN promoter hypermethylation was significantly increased in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) compared to normal breast tissues (OR =22.53, P=0.0002 and OR =22.86, P<0.00001, respectively). However, the frequency of PTEN promoter hypermethylation was similar between IDC and DCIS. Additionally, PTEN methylation was not significantly correlated to estrogen receptor (ER) or human epidermal growth factor type 2 (HER-2) status in patients with BC. CONCLUSION: PTEN promoter hypermethylation is significantly associated with the risk of DCIS and IDC, suggesting PTEN promoter hypermethylation is a valuable biomarker for diagnosis of BC. PMID- 27672336 TI - Lyme disease: the promise of Big Data, companion diagnostics and precision medicine. AB - Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. Recent studies based on Big Data registries show that >300,000 people are diagnosed with Lyme disease each year in the USA, and up to two-thirds of individuals infected with B. burgdorferi will fail conventional 30 year-old antibiotic therapy for Lyme disease. In addition, animal and human evidence suggests that sexual transmission of the Lyme spirochete may occur. Improved companion diagnostic tests for Lyme disease need to be implemented, and novel treatment approaches are urgently needed to combat the epidemic. In particular, therapies based on the principles of precision medicine could be modeled on successful "designer drug" treatment for HIV/AIDS and hepatitis C virus infection featuring targeted protease inhibitors. The use of Big Data registries, companion diagnostics and precision medicine will revolutionize the diagnosis and treatment of Lyme disease. PMID- 27672334 TI - Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas. AB - Surgical resection is typically the first line of treatment for gliomas. However, the neurosurgeon faces a major challenge in achieving maximal resection in high grade gliomas as these infiltrative tumors make it difficult to discern tumor margins from normal brain with conventional white-light microscopy alone. To aid in resection of these infiltrative tumors, fluorescence-guided surgery has gained much popularity in intraoperative visualization of malignant gliomas, with 5 aminolevulinic acid (5-ALA) leading the way. First introduced in an article in Neurosurgery, 5-ALA has since become a safe, effective, and inexpensive method to visualize and improve resection of gliomas. This has undoubtedly led to improvements in the clinical course of patients as demonstrated by the increased overall and progression-free survival in patients with such devastating disease. This literature review aims to discuss the major studies and trials demonstrating the clinical utility of 5-ALA and its ability to aid in complete resection of malignant gliomas. PMID- 27672337 TI - Cost versus utility of aclidinium bromide 400 ug plus formoterol fumarate dihydrate 12 ug compared to aclidinium bromide 400 ug alone in the management of moderate-to-severe COPD. AB - PURPOSE: Aclidinium-formoterol 400/12 ug is a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist in a fixed-dose combination used in the management of patients with COPD. This study aimed to assess the cost effectiveness of aclidinium-formoterol 400/12 ug against the long-acting muscarinic antagonist aclidinium bromide 400 ug. MATERIALS AND METHODS: A five health-state Markov transition model with monthly cycles was developed using MS Excel to simulate patients with moderate-to-severe COPD and their initial lung function improvement following treatment with aclidinium-formoterol 400/12 ug or aclidinium 400 ug. Health states were based on severity levels defined by Global Initiative for Chronic Obstructive Lung Disease 2010 criteria. The analysis was a head-to-head comparison without step-up therapy, from the NHS Scotland perspective, over a 5-year time horizon. Clinical data on initial lung-function improvement were provided by a pooled analysis of the ACLIFORM and AUGMENT trials. Management, event costs, and utilities were health state-specific. Costs and effects were discounted at an annual rate of 3.5%. The outcome of the analysis was expressed as cost (UKL) per quality-adjusted life-year (QALY) gained. The analysis included one way and probabilistic sensitivity analyses to investigate the impact of parameter uncertainty on model outputs. RESULTS: Aclidinium-formoterol 400/12 ug provided marginally higher costs (L41) and more QALYs (0.014), resulting in an incremental cost-effectiveness ratio of L2,976/QALY. Sensitivity analyses indicated that results were robust to key parameter variations, and the main drivers were: mean baseline forced expiratory volume in 1 second (FEV1), risk of exacerbation, FEV1 improvement from aclidinium formoterol 400/12 ug, and lung-function decline. The probability of aclidinium formoterol 400/12 ug being cost-effective (using a willingness-to-pay threshold of L20,000/QALY) versus aclidinium 400 ug was 79%. CONCLUSION: In Scotland, aclidinium-formoterol 400/12 ug can be considered a cost-effective treatment option compared to aclidinium 400 ug alone in patients with moderate-to-severe COPD. PMID- 27672339 TI - Clinical usefulness of red cell distribution width to angiographic severity and coronary stent thrombosis. AB - BACKGROUND: Red cell distribution width (RDW) is a quantitative measurement and shows heterogeneity of red blood cell size in peripheral blood. RDW has recently been associated with cardiovascular events and cardiovascular diseases, and it is a novel predictor of mortality. In this study, we aimed to evaluate the clinical usefulness of measuring RDW in patients with coronary stent thrombosis. PATIENTS AND METHODS: We retrospectively reviewed 3,925 consecutive patients who presented with acute coronary syndrome and who underwent coronary angiography at the Siyami Ersek Hospital between May 2011 and December 2013. Of the 3,925 patients, 73 patients (55 males, mean age 59+/-11 years, 55 with ST elevated myocardial infarction) with stent thrombosis formed group 1. Another 54 consecutive patients who presented with acute coronary syndrome (without coronary stent thrombosis, 22 patients with ST elevated myocardial infarction, 44 males, mean age 54+/-2 years) and underwent percutaneous coronary intervention in May 2011 formed group 2. Data were collected from all groups for 2 years. The RDW values were calculated from patients 1 month later at follow-up. Syntax scores were calculated for all the patients. The patients were also divided as low syntax score group and moderate high syntax score group. RESULTS: The patients in group 1 with stent thrombosis had significantly higher RDW level (13.85) than the patients in group 2 without stent thrombosis (12) (P<0.001). In addition, in all study patients, the moderate high syntax score group had significantly higher RDW level (13.6) than the low syntax score group (12.9) (P=0.009). A positive correlation was determined between RDW and syntax scores (r=0.204). CONCLUSION: RDW is a new marker of poor prognosis in coronary artery disease. Increased RDW level is correlated with angiographic severity of coronary artery disease, and RDW may be an important clinical marker of coronary stent thrombosis in patients undergoing coronary intervention. PMID- 27672340 TI - Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis. AB - OBJECTIVES: Effective postoperative pain management is crucial in the care of surgical patients. Opioids, which are commonly used in managing postoperative pain, have a potential for tolerance and addiction, along with sedating side effects. Gabapentin's use as a multimodal analgesic regimen to treat neuropathic pain has been documented as having favorable side effects. This meta-analysis examined the use of preoperative gabapentin and its impact on postoperative opioid consumption. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify randomized control trials that evaluated preoperative gabapentin on postoperative opioid consumption. The outcomes of interest were cumulative opioid consumption following the surgery and the incidence of vomiting, somnolence, and nausea. RESULTS: A total of 1,793 patients involved in 17 randomized control trials formed the final analysis for this study. Postoperative opioid consumption was reduced when using gabapentin within the initial 24 hours following surgery (standard mean difference -1.35, 95% confidence interval [CI]: -1.96 to -0.73; P<0.001). There was a significant reduction in morphine, fentanyl, and tramadol consumption (P<0.05). While a significant increase in postoperative somnolence incidence was observed (relative risk 1.30, 95% CI: 1.10-1.54, P<0.05), there were no significant effects on postoperative vomiting and nausea. CONCLUSION: The administration of preoperative gabapentin reduced the consumption of opioids during the initial 24 hours following surgery. The reduction in postoperative opioids with preoperative gabapentin increased postoperative somnolence, but no significant differences were observed in nausea and vomiting incidences. The results from this study demonstrate that gabapentin is more beneficial in mastectomy and spinal, abdominal, and thyroid surgeries. Gabapentin is an effective analgesic adjunct, and clinicians should consider its use in multimodal treatment plans among patients undergoing elective surgery. PMID- 27672338 TI - The potential use of biomarkers in predicting contrast-induced acute kidney injury. AB - Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-beta-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. PMID- 27672341 TI - Thermal temporal summation and decay of after-sensations in temporomandibular myofascial pain patients with and without comorbid fibromyalgia. AB - INTRODUCTION: Chronic myofascial temporomandibular disorders (TMD) may have multiple etiological and maintenance factors. One potential factor, central pain sensitization, was quantified here as the response to the temporal summation (TS) paradigm, and that response was compared between case and control groups. OBJECTIVES: As previous research has shown that fibromyalgia (FM) is diagnosed in20% of TMD patients, Aim 1 determined whether central sensitization is found preferentially in myofascial TMD cases that have orofacial pain as a regional manifestation of FM. Aim 2 determined if the report of after-sensations (AS) following TS varied depending on whether repeated stimuli were rated as increasingly painful. METHODS: One hundred sixty-eight women, 43 controls, 100 myofascial TMD-only cases, and 25 myofascial TMD + FM cases, were compared on thermal warmth and pain thresholds, thermal TS, and decay of thermal AS. All cases met Research Diagnostic Criteria for TMD; comorbid cases also met the 1990 American College of Rheumatology criteria for FM. RESULTS: Pain thresholds and TS were similar in all groups. When TS was achieved (~60%), significantly higher levels of AS were reported in the first poststimulus interval, and AS decayed more slowly over time, in myofascial TMD cases than controls. By contrast, groups showed similar AS decay patterns following steady state or decreasing responses to repetitive stimulation. CONCLUSION: In this case-control study, all myofascial TMD cases were characterized by a similar delay in the decay of AS. Thus, this indicator of central sensitization failed to suggest different pain maintenance factors in myofascial TMD cases with and without FM. PMID- 27672342 TI - Factors associated with institutional delivery service utilization in Ethiopia. AB - BACKGROUND: Most obstetric complications occur unpredictably during the time of delivery, but they can be prevented with proper medical care in the health facilities. Despite the Ethiopian government's efforts to expand health service facilities and promote health institution-based delivery service in the country, an estimated 85% of births still take place at home. OBJECTIVE: The review was conducted with the aim of generating the best evidence on the determinants of institutional delivery service utilization in Ethiopia. METHODS: The reviewed studies were accessed through electronic web-based search strategy from PubMed, HINARI, Mendeley reference manager, Cochrane Library for Systematic Reviews, and Google Scholar. Review Manager V5.3 software was used for meta-analysis. Mantel Haenszel odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. Heterogeneity of the study was assessed using I (2) test. RESULTS: People living in urban areas (OR =13.16, CI =1.24, 3.68), with primary and above educational level of the mother and husband (OR =4.95, CI =2.3, 4. 8, and OR =4.43, CI =1.14, 3.36, respectively), who encountered problems during pregnancy (OR =2.83, CI =4.54, 7.39), and living at a distance <5 km from nearby health facility (OR =2.6, CI =3.33, 6.57) showed significant association with institutional delivery service utilization. Women's autonomy was not significantly associated with institutional delivery service utilization. CONCLUSION AND RECOMMENDATION: Distance to health facility and problems during pregnancy were factors positively and significantly associated with institutional delivery service utilization. Promoting couples education beyond primary education regarding the danger signs of pregnancy and benefits of institutional delivery through available communication networks such as health development army and promotion of antenatal care visits and completion of four standard visits by pregnant women were recommended. PMID- 27672343 TI - Three cases of ocular syphilis and the resurgence of the disease in Queensland. AB - The past few years has seen a resurgence of syphilis. It is predominantly associated within men who have sex with men and also within heterosexual Indigenous Australians. Possessing the ability to mimic a variety of ocular diseases, it typically manifests as uveitis, although it can affect any structure within the eye. Thus, a high degree of clinical suspicion by ophthalmologists is required to prevent disease progression and ocular morbidity. Patients require prolonged antibiotic treatment with intravenous benzylpenicillin and outpatient monitoring to successfully resolve the infection. We describe a case series of ocular syphilis presentations in Queensland, Australia. PMID- 27672344 TI - Exposure-response analysis to assess the concentration-QTc relationship of CC 122. AB - CC-122 hydrochloride is a novel pleiotropic pathway modifier compound that binds cereblon, a substrate receptor of the Cullin 4 RING E3 ubiquitin ligase complex. CC-122 has multiple activities including modulation of immune cells, antiproliferative activity of multiple myeloma and lymphoma cells, and antiangiogenic activity. CC-122 is being developed as an oncology treatment for hematologic malignancies and advanced solid tumors. Cardiovascular and vital sign assessments of CC-122 have been conducted in hERG assays in vitro and in a 28-day good laboratory practice monkey study with negative signals. To assess the potential concentration-QTc relationship in humans and to ascertain or exclude a small QT effect by CC-122, a plasma concentration exposure- and DeltaQTcF response model of CC-122 was developed. Intensive CC-122 concentration and paired triplicate electrocardiogram data from a single ascending dose study were included in the analysis. The parameters included in the final linear exposure response model are intercept, slope, and treatment effect. The slope estimate of 0.0201 with 90% CI of (0.009, 0.035) indicates a weak relationship between DeltaQTcF and CC-122 concentration. The upper bounds of the 90% CI of the model predicted DeltaDeltaQTcF effect at C max from the 4 mg clinical dose and the supratherapeutic dose of 15 mg (1.18 ms and 8.76 ms, respectively) are <10 ms threshold, suggesting that the risk of CC-122 QT prolongation effect at the relevant therapeutic dose range from 1 mg to 4 mg is low. PMID- 27672345 TI - Grappling with the issue of homosexuality: perceptions, attitudes, and beliefs among high school students in Kenya. AB - While the past decade has seen an improvement in attitudes toward homosexuality, negative attitudes are still prevalent in many parts of the world. In general, increased levels of education tend to be predictive of relatively positive attitudes toward homosexuality. However, in most sub-Saharan countries, it is still believed that people are born heterosexual and that nonheterosexuals are social deviants who should be prosecuted. One such country is Kenya, where homosexuality is illegal and attracts a fine or jail term. The purpose of this study was to examine high school students' perceptions of homosexuality in Kenya. The participants included 1,250 high school students who completed a questionnaire on perceptions of homosexuality. The results showed that 41% claimed homosexuality is practiced in schools and 61% believed homosexuality is practiced mostly in single-sex boarding schools. Consistently, 52% believed sexual starvation to be the main cause of homosexuality. Also, 95% believed homosexuality is abnormal, 60% believed students who engage in homosexuality will not change to heterosexuality after school, 64% believed prayers can stop homosexuality, and 86% believed counseling can change students' sexual orientation. The consequences for homosexuality included punishment (66%), suspension from school (61%), and expulsion from school (49%). Significant gender and grade differences were found. The implications of the study findings are discussed. PMID- 27672347 TI - The transition from high school to university: a medical student's perspective. PMID- 27672346 TI - Patient-reported symptom distress, and most bothersome issues, before and during cancer treatment. AB - INTRODUCTION: Frequently reported symptoms and treatment side effects may not be the most bothersome issues to patients with cancer. The purpose of this study was to investigate patient-reported symptom distress and bothersome issues among participants with cancer. METHODS: Participants completed the Symptom Distress Scale-15 before treatment (T1) and during cancer treatment (T2) and reported up to two most bothersome issues among symptoms rated with moderate-to-severe distress. We compared symptom ratings and perceived bother and explored two approaches predicting patients' most bothersome issues: worst absolute symptom score or worst change from pretreatment. RESULTS: Significantly, (P<=0.0002) more patients reported moderate-to-severe distress at T2 for eight of 13 symptoms. At T1, 81% of patients reported one and 56% reported multiple symptoms with moderate to-severe distress, while at T2, 89% reported one and 69% reported multiple symptoms with moderate-to-severe distress. Impact on sexual activity/interest, pain, fatigue, and insomnia were the most prevalent symptoms with moderate-to severe distress. Fatigue, pain, and insomnia were perceived most often as bothersome. When one symptom was rated moderate-to-severe, predictive accuracy of the absolute score was 46% and 48% (T1 & T2) and 38% with the change score (T2 T1). When two or more symptoms were rated moderate-to-severe, predictive accuracy of the absolute score was 76% and 79% (T1 & T2) and 70% with the change score (T2 T1). CONCLUSION: More patients experienced moderate-to-severe symptom distress after treatment initiation. Patient identification of bothersome issues could not be assumed based on prevalence of symptoms reported with moderate-to-severe distress. The absolute symptom distress scores identified patients' most bothersome issues with good accuracy, outperforming change scores. PMID- 27672348 TI - Improving the Treatment and Assessment of Moderate and Severe Pain in a Pediatric Emergency Department. AB - Background. The Janeway Children's Hospital previously enacted a number of measures to improve pain management for patients in its emergency department (ED). While improvements were demonstrated, rates for the timely assessment and treatment of pain remain below standards of care. Objectives. The study objectives are to investigate the impact of the previous attempts to improve the treatment of pain and to explore ways to further improve pain management in the ED. Methods. Key informant interviews and a focus group were conducted with nurses, physicians, and parents whose children were identified as having severe pain. Results. Interviews were conducted with 31 parents or children, 9 physicians, and 8 nurses. The focus group was attended by 15 nurses. Previous initiatives were viewed as improvements. Continued barriers include difficulties in accurately capturing the level of pain, issues in treating pain for specific types of patients, and inadequacy in addressing patients in severe pain. Conclusion. Changes in pain treatment protocols can result in positive impacts but are likely insufficient on their own to achieve desired standards of care. Consistent measurement and engagement with staff can identify additional opportunities for improving pain management within an ED setting. PMID- 27672349 TI - Prevalence of tuberculosis and associated risk factors in the Central Prison of Mbuji-Mayi, Democratic Republic of Congo. AB - BACKGROUND: Tuberculosis still remains a major public health concern in several provinces of the Democratic Republic of Congo, especially in prison settings. The present study aimed at determining tuberculosis (TB) prevalence and associated risk factors in inmates of the Mbuji-Mayi Central Prison. METHODS: This cross sectional study was performed over a 6-month period (January to June 2015) in Mbuji-Mayi Central Prison. A total of 733 inmates were screened systematically for TB. The diagnosis was based on clinical examination and bacteriological tests. RESULTS: Tuberculosis was diagnosed in 130 inmates, what amounts to a 17.7 % prevalence (95 % confidence interval [CI] 15.1-20.6 %). The mean age +/- SD of infected inmates was 31 +/- 9.5 years old, and 94.8 % of them were male. Inmates were detained for a median period of 24 months (range: 3 months to 12 years). A cough lasting more than 2 weeks, body temperature higher than 39 degrees C, and weight loss were the predominating clinical signs. Factors independently associated with TB infection were overcrowding; highest population attributable fraction ([PAF] 88.2 %; adjusted odds ratio [OR] 9.8 [95 % CI 3.1-31.6]); malnutrition (body mass index of less than 18.5 kg/m(2)) (PAF 35.6 %; adjusted OR 2.1 [1.3-3.0]); and a detention period equal to or greater than 12 months (PAF 38.7 %; adjusted OR 2.1 [1.4-3.1]). CONCLUSIONS: Improving detention and sanitary conditions, as well as providing an adequate and early healthcare, are urgently needed to reduce TB prevalence in the prison environment. PMID- 27672350 TI - Unusual presentation of non-small cell lung cancer with clival metastases: Case report. AB - A 37-year-old female with unusual presentation of metastatic non-small cell lung cancer (NSCLC), as she presented with symptoms related to clival bone metastases. This case highlights the unpredictable presentations and the variety of metastatic sites of which metastatic NSCLC could be presented. PMID- 27672351 TI - Establishment of a Simple and Quick Method for Detecting Extended-Spectrum beta Lactamase (ESBL) Genes in Bacteria. AB - Extended-spectrum beta-lactamase (ESBL) genes that render bacteria resistant to antibiotics are commonly detected using phenotype testing, which is time consuming and not sufficiently accurate. To establish a better method, we used phenotype testing to identify ESBL-positive bacterial strains and conducted PCR to screen for TEM (named after the patient Temoneira who provided the first sample), sulfhydryl reagent variable (SHV), cefotaxime (CTX)-M-1, and CTX-M-9, the 4 most common ESBL types and subtypes. We then performed multiplex PCR with 1 primer containing a biotin and hybridized the PCR products with gene-specific probes that were coupled with microbeads and coated with a specific fluorescence. The hybrids were linked to streptavidin-R-phycoerythrins (SA-PEs) and run through a flow cytometer, which sorted the fluorescently dyed microbeads and quantified the PEs. The results from single PCR, multiplex PCR, and cytometry were consistent with each other. We used this method to test 169 clinical specimens that had been determined for phenotypes and found 154 positive for genotypes, including 30 of the 45 samples that were negative for phenotypes. The CTX-M genotype tests alone, counting both positive and negative cases, showed 99.41% (168/169) consistency with the ESBL phenotype test. Thus, we have established a multiplex-PCR system as a simple and quick method that is high throughput and accurate for detecting 4 common ESBL types and subtypes. PMID- 27672352 TI - Monitoring Error Rates In Illumina Sequencing. AB - Guaranteeing high-quality next-generation sequencing data in a rapidly changing environment is an ongoing challenge. The introduction of the Illumina NextSeq 500 and the depreciation of specific metrics from Illumina's Sequencing Analysis Viewer (SAV; Illumina, San Diego, CA, USA) have made it more difficult to determine directly the baseline error rate of sequencing runs. To improve our ability to measure base quality, we have created an open-source tool to construct the Percent Perfect Reads (PPR) plot, previously provided by the Illumina sequencers. The PPR program is compatible with HiSeq 2000/2500, MiSeq, and NextSeq 500 instruments and provides an alternative to Illumina's quality value (Q) scores for determining run quality. Whereas Q scores are representative of run quality, they are often overestimated and are sourced from different look-up tables for each platform. The PPR's unique capabilities as a cross-instrument comparison device, as a troubleshooting tool, and as a tool for monitoring instrument performance can provide an increase in clarity over SAV metrics that is often crucial for maintaining instrument health. These capabilities are highlighted. PMID- 27672353 TI - Anxiety sensitivity and smoking variability among treatment seeking smokers. AB - OBJECTIVES: Anxiety sensitivity (AS) is associated with poor smoking cessation outcomes. One reason may be that smokers with high AS smoke differently (i.e., to manage negative affect and uncomfortable bodily sensations) than other smokers, leading to stronger addiction (due to an affect/sensation based and thereby highly variable rather than a regular smoking routine). Thus, we examined the relationship between AS and smoking variability in a group of treatment-seeking smokers. METHODS: Participants (N = 136; 52.2% female; Mage = 44.19 years, SD = 11.29) were daily smokers with elevated AS (AS>=20 on the Anxiety Sensitivity Index 16-item at prescreen) recruited as part of a larger randomized controlled trial for smoking cessation. Most participants were Caucasian (73%), educated (with 76% attending some college), unmarried (73%), and employed full-time (56%). They smoked, on average, 17 cigarettes per day. RESULTS: Consistent with prediction, a regression analysis of baseline assessments and a longitudinal analysis with multilevel modeling (MLM) both showed higher AS was associated with greater variability in cigarettes smoked per day while controlling for gender, age, ethnicity, and income. CONCLUSIONS: This finding encourages investigation of how AS might interact with clinical strategies using a fixed smoking taper as part of quit attempts. PMID- 27672354 TI - Two- and three-year-olds track a single meaning during word learning: Evidence for Propose-but-verify. AB - A child word-learning experiment is reported that examines 2- and 3-year-olds' ability to learn the meanings of novel words across multiple, referentially ambiguous, word occurrences. Children were told they were going on an animal safari in which they would learn the names of unfamiliar animals. Critical trial sequences began with hearing a novel word (e.g., "I see a dax! Point to the dax!") while seeing photos of two unfamiliar animals. After responding and performing on two filler trials with known animals, participants encountered the novel word again ("I see another dax! Point to the dax!") in one of two experimental conditions. In the Same condition, participants saw the animal they pointed to previously when hearing "dax" alongside another unfamiliar animal that had been seen before but not paired with "dax". In the Switch condition, participants saw the animal they had not pointed to previously alongside the unfamiliar animal. Children were well above chance on Same trials, but at chance on Switch trials. Thus, although children could remember a previously selected referent and use it to inform later referent selection (Same condition), a potential referent that was not previously selected and merely co-occurred with the target word (Switch condition) was either not remembered, or simply deemed irrelevant to word meaning. This finding suggests young children do not store multiple possible meanings from a single word occurrence, but rather restrict learning to what they deemed to be the unique referent of the novel word in the moment, testing that word-meaning hypothesis on the next occurrence. PMID- 27672356 TI - Parent-Child Discrepancies in Reporting of Child Depression in Ethnic Groups. PMID- 27672357 TI - New Insights into Clinical Characteristics of Gilles de la Tourette Syndrome: Findings in 1032 Patients from a Single German Center. AB - BACKGROUND: Gilles de la Tourette syndrome (TS) is a complex neuropsychiatric disorder defined by the presence of motor and phonic tics, but often associated with psychiatric comorbidities. The main objective of this study was to explore the clinical presentation and comorbidities of TS. METHOD: We analyzed clinical data obtained from a large sample (n = 1032; 529 children and 503 adults) of patients with tic disorders from one single German TS center assessed by one investigator. Data was collected with the help of an expert-reviewed semi structured interview, designed to assess tic severity and certain comorbidities. Group comparisons were carried out via independent sample t-tests and chi-square tests. RESULTS: The main findings of the study are: (1) tic severity is associated with the presence of premonitory urges (PU), copro-, echo-, and paliphenomena and the number of comorbidities, but not age at tic onset; it is higher in patients with comorbid obsessive-compulsive disorder (OCD) than in patients with comorbid attention deficit/hyperactivity disorder (ADHD). (2) PU were found to be highly associated with "not just right experiences" and to emerge much earlier than previously thought alongside with the ability to suppress tics (PU in >60% and suppressibility in >75% at age 8-10 years). (3) Self-injurious behavior (SIB) is highly associated with complex motor tics and coprophenomena, but not with OCD/obsessive-compulsive behavior (OCB). While comorbid ADHD is associated with a lower ability to suppress tics, comorbid depression is associated with sleeping problems. DISCUSSION: Our results demonstrate that tic severity is not influenced by age at onset. From our data, it is suggested that PU represent a specific type of "not just right experience" that is not a prerequisite for tic suppression. Comorbid ADHD reduces patients' ability of successful tic suppression. Our data suggest that SIB belongs to the coprophenomena spectrum and hence should be conceptualized as a complex tic rather than a compulsion. Finally, this study strongly supports the hypothesis that TS+OCD is a more severe form of TS and that comorbid OCD/OCB, depression, and anxiety belong to the TS spectrum, while ADHD should be better conceptualized as a separate problem. PMID- 27672359 TI - DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees. AB - The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naive odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naive odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes. PMID- 27672358 TI - Aripiprazole Improves Associated Comorbid Conditions in Addition to Tics in Adult Patients with Gilles de la Tourette Syndrome. AB - Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4-6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics in patients with GTS. It can be hypothesized that these beneficial effects are related to aripiprazole's adaptive pharmacological profile, which exhibits an influence on the dopaminergic as well as a number of other neurotransmitter systems. For the first time, our data provide evidence that patients' decision making process for or against medical treatment is influenced by other factors than tic severity and QoL. PMID- 27672360 TI - Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways. AB - Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM-5 MUM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP 1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs) frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9-39) (1 MUM). Intracellular application of the G-protein inhibitor GDP-beta-S (2 mM) impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP 1 on GnRH neurons. Blockade of nitric-oxide (NO) synthesis by Nomega-Nitro-L arginine methyl ester hydrochloride (L-NAME; 100 MUM) or N(5) [Imino(propylamino)methyl]-L-ornithine hydrochloride (NPLA; 1 MUM) or intracellular scavenging of NO by 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (CPTIO; 1 mM) partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using cannabinoid receptor type-1 (CB1) inverse agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl) pyrazole 3-carboxamide (AM251; 1 MUM). Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the transient receptor potential vanilloid 1 (TRPV1)-antagonist 2E-N-(2, 3-Dihydro-1,4-benzodioxin-6-yl) 3-[4-(1, 1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 MUM) or the fatty acid amide hydrolase (FAAH)-inhibitor PF3845 (5 MUM) impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2 arachidonoylglycerol (2-AG) production. Furthermore, GLP-1 immunoreactive (IR) axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and neuronal NO synthase (nNOS) mRNAs in GnRH GFP neurons. Immuno-electron microscopic analysis revealed the presence of nNOS protein in GnRH neurons. These results indicate that GLP-1 exerts direct facilitatory actions via GLP-1R on GnRH neurons and modulates NO and 2-AG retrograde signaling mechanisms that control the presynaptic excitatory GABAergic inputs to GnRH neurons. PMID- 27672361 TI - Transgenic GDNF Positively Influences Proliferation, Differentiation, Maturation and Survival of Motor Neurons Produced from Mouse Embryonic Stem Cells. AB - Embryonic stem cells (ESC) are pluripotent and thus can differentiate into every cell type present in the body. Directed differentiation into motor neurons (MNs) has been described for pluripotent cells. Although neurotrophic factors promote neuronal survival, their role in neuronal commitment is elusive. Here, we developed double-transgenic lines of mouse ESC (mESC) that constitutively produce glial cell line-derived neurotrophic factor (GDNF) and also contain a GFP reporter, driven by HB9, which is expressed only by postmitotic MNs. After lentiviral transduction, ESC lines integrated and expressed the human GDNF (hGDNF) gene without altering pluripotency markers before differentiation. Further, GDNF-ESC showed significantly higher spontaneous release of this neurotrophin to the medium, when compared to controls. To study MN induction, control and GDNF cell lines were grown as embryoid bodies and stimulated with retinoic acid and Sonic Hedgehog. In GDNF-overexpressing cells, a significant increase of proliferative Olig2+ precursors, which are specified as spinal MNs, was found. Accordingly, GDNF increases the yield of cells with the pan motor neuronal markers HB9, monitored by GFP expression, and Isl1. At terminal differentiation, almost all differentiated neurons express phenotypic markers of MNs in GDNF cultures, with lower proportions in control cells. To test if the effects of GDNF were present at early differentiation stages, exogenous recombinant hGDNF was added to control ESC, also resulting in enhanced MN differentiation. This effect was abolished by the co-addition of neutralizing anti-GDNF antibodies, strongly suggesting that differentiating ESC are responsive to GDNF. Using the HB9::GFP reporter, MNs were selected for electrophysiological recordings. MNs differentiated from GDNF-ESC, compared to control MNs, showed greater electrophysiological maturation, characterized by increased numbers of evoked action potentials (APs), as well as by the appearance of rebound APs, sag inward rectification, spike frequency adaptation and spontaneous synaptic potentials. Upon challenge with kainate, GDNF-overexpressing cells are more resistant to excitotoxicity than control MNs. Together these data indicate that GDNF promotes proliferation of MN-committed precursors, promotes neuronal differentiation, enhances maturation, and confers neuroprotection. GDNF expressing ESC can be useful in studies of development and disease. PMID- 27672362 TI - Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of DeltaFosB in the Nucleus Accumbens. AB - While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to DeltaFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure DeltaFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of DeltaFosB in the nucleus accumbens. Our data suggest that DeltaFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. PMID- 27672363 TI - Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia. AB - Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 * 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic activation of GPe neurons does not impact the learning ability but decreases reaction time as reported in DBS patients. These results suggest a probable role of electrode and antidromic activation in modulating the STN activity and eventually affecting the patient's performance on PLT. PMID- 27672364 TI - Efficient Integration of Coupled Electrical-Chemical Systems in Multiscale Neuronal Simulations. AB - Multiscale modeling and simulations in neuroscience is gaining scientific attention due to its growing importance and unexplored capabilities. For instance, it can help to acquire better understanding of biological phenomena that have important features at multiple scales of time and space. This includes synaptic plasticity, memory formation and modulation, homeostasis. There are several ways to organize multiscale simulations depending on the scientific problem and the system to be modeled. One of the possibilities is to simulate different components of a multiscale system simultaneously and exchange data when required. The latter may become a challenging task for several reasons. First, the components of a multiscale system usually span different spatial and temporal scales, such that rigorous analysis of possible coupling solutions is required. Then, the components can be defined by different mathematical formalisms. For certain classes of problems a number of coupling mechanisms have been proposed and successfully used. However, a strict mathematical theory is missing in many cases. Recent work in the field has not so far investigated artifacts that may arise during coupled integration of different approximation methods. Moreover, in neuroscience, the coupling of widely used numerical fixed step size solvers may lead to unexpected inefficiency. In this paper we address the question of possible numerical artifacts that can arise during the integration of a coupled system. We develop an efficient strategy to couple the components comprising a multiscale test problem in neuroscience. We introduce an efficient coupling method based on the second-order backward differentiation formula (BDF2) numerical approximation. The method uses an adaptive step size integration with an error estimation proposed by Skelboe (2000). The method shows a significant advantage over conventional fixed step size solvers used in neuroscience for similar problems. We explore different coupling strategies that define the organization of computations between system components. We study the importance of an appropriate approximation of exchanged variables during the simulation. The analysis shows a substantial impact of these aspects on the solution accuracy in the application to our multiscale neuroscientific test problem. We believe that the ideas presented in the paper may essentially contribute to the development of a robust and efficient framework for multiscale brain modeling and simulations in neuroscience. PMID- 27672366 TI - Editorial: Inter-healthcare Professions Collaboration: Educational and Practical Aspects and New Developments. PMID- 27672365 TI - Ca(2+)-Currents in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Effects of Two Different Culture Conditions. AB - Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) provide a unique opportunity to study human heart physiology and pharmacology and repair injured hearts. The suitability of hiPSC-CM critically depends on how closely they share physiological properties of human adult cardiomyocytes (CM). Here we investigated whether a 3D engineered heart tissue (EHT) culture format favors maturation and addressed the L-type Ca(2+)-current (ICa,L) as a readout. The results were compared with hiPSC-CM cultured in conventional monolayer (ML) and to our previous data from human adult atrial and ventricular CM obtained when identical patch-clamp protocols were used. HiPSC-CM were two- to three-fold smaller than adult CM, independently of culture format [capacitance ML 45 +/- 1 pF (n = 289), EHT 45 +/- 1 pF (n = 460), atrial CM 87 +/- 3 pF (n = 196), ventricular CM 126 +/- 8 pF (n = 50)]. Only 88% of ML cells showed ICa, but all EHT. Basal ICa density was 10 +/- 1 pA/pF (n = 207) for ML and 12 +/- 1 pA/pF (n = 361) for EHT and was larger than in adult CM [7 +/- 1 pA/pF (p < 0.05, n = 196) for atrial CM and 6 +/- 1 pA/pF (p < 0.05, n = 47) for ventricular CM]. However, ML and EHT showed robust T-type Ca(2+)-currents (ICa,T). While (-)-Bay K 8644, that activates ICa,L directly, increased ICa,Lto the same extent in ML and EHT, beta1- and beta2-adrenoceptor effects were marginal in ML, but of same size as ( )-Bay K 8644 in EHT. The opposite was true for serotonin receptors. Sensitivity to beta1 and beta2-adrenoceptor stimulation was the same in EHT as in adult CM ( logEC50: 5.9 and 6.1 for norepinephrine (NE) and epinephrine (Epi), respectively), but very low concentrations of Rp-8-Br-cAMPS were sufficient to suppress effects (-logEC50: 5.3 and 5.3 respectively for NE and Epi). Taken together, hiPSC-CM express ICa,L at the same density as human adult CM, but, in contrast, possess robust ICa,T. Increased effects of catecholamines in EHT suggest more efficient maturation. PMID- 27672368 TI - GlyT2-Dependent Preservation of MECP2-Expression in Inhibitory Neurons Improves Early Respiratory Symptoms but Does Not Rescue Survival in a Mouse Model of Rett Syndrome. AB - Mutations in methyl-CpG-binding protein 2 (MECP2) gene have been shown to manifest in a neurodevelopmental disorder that is called Rett syndrome. A typical problem that occurs during development is a disturbance of breathing. To address the role of inhibitory neurons, we generated a mouse line that restores MECP2 in inhibitory neurons in the brainstem by crossbreeding a mouse line that expresses the Cre-recombinase (Cre) in inhibitory neurons under the control of the glycine transporter 2 (GlyT2, slc6a5) promotor (GlyT2-Cre) with a mouse line that has a floxed-stop mutation of the Mecp2 gene (Mecp2 (stop/y)). Unrestrained whole-body plethysmography at postnatal day P60 revealed a low respiratory rate and prolonged respiratory pauses in Mecp2 (stop/y) mice. In contrast, GlyT2-Cre positive Mecp2 (stop/y) mice (Cre(+) ; Mecp2 (stop/y)) showed greatly improved respiration and were indistinguishable from wild type littermates. These data support the concept that alterations in inhibitory neurons are important for the development of the respiratory phenotype in Rett syndrome. PMID- 27672367 TI - Macropinocytosis Exploitation by Cancers and Cancer Therapeutics. AB - Macropinocytosis has long been known as a primary method for cellular intake of fluid-phase and membrane-bound bulk cargo. This review seeks to re-examine the latest studies to emphasize how cancers exploit macropinocytosis to further their tumorigenesis, including details in how macropinocytosis can be adapted to serve diverse functions. Furthermore, this review will also cover the latest endeavors in targeting macropinocytosis as an avenue for novel therapeutics. PMID- 27672370 TI - The Environmental Plasticity of Diverse Body Color Caused by Extremely Long Photoperiods and High Temperature in Saccharosydne procerus (Homoptera: Delphacidae). AB - Melanization reflects not only body color variation but also environmental plasticity. It is a strategy that helps insects adapt to environmental change. Different color morphs may have distinct life history traits, e.g., development time, growth rate, and body weight. The green slender planthopper Saccharosydne procerus (Matsumura) is the main pest of water bamboo (Zizania latifolia). This insect has two color morphs. The present study explored the influence of photoperiod and its interaction with temperature in nymph stage on adult melanism. Additionally, the longevity, fecundity, mating rate, and hatching rate of S. procerus were examined to determine whether the fitness of the insect was influenced by melanism under different temperature and photoperiod. The results showed that a greater number of melanic morphs occurred if the photoperiod was extremely long. A two-factor ANOVA showed that temperature and photoperiod both have a significant influence on melanism. The percentages of variation explained by these factors were 45.53 and 48.71%, respectively. Moreover, melanic morphs had greater advantages than non-melanic morphs under an environmental regime of high temperatures and a long photoperiod, whereas non-melanic morphs were better adapted to cold temperatures and a short photoperiod. These results cannot be explained by the thermal melanism hypothesis. Thus, it may be unavailable to seek to explain melanism in terms of only one hypothesis. PMID- 27672369 TI - Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne(r): Implication for Atherosclerotic Plaque Treatment. AB - Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. AIM: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne(r)), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. METHODS AND RESULTS: Visudyne(r) (100, 200, and 500 ng/ml) was perfused for 5-30 min in atherosclerotic aorta isolated from ApoE(-/-) mice. The fluorescence Intensity (FI) after 15 min of Visudyne(r) perfusion increased with doses of 100 (FI-5.5 +/ 1.8), 200 (FI-31.9 +/- 1.9) or 500 ng/ml (FI-42.9 +/- 1.2). Visudyne(r) (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 +/- 2.5) to 10 min (FI-23.3 +/- 3.0) and 15 min (FI-42.9 +/- 3.4) before reaching saturation at 30 min (FI-39.3 +/- 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm(2), irradiance-334 mW/cm(2)) was applied immediately after Visudyne(r) perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 +/- 1.8, 25.3 +/- 5.5, 43.4 +/- 13.9) and apoptotic cells (TUNEL; 2.5 +/- 1.6, 41.3 +/- 15.3, 58.9 +/- 6%), mainly plaque macrophages (immunostaining; 0.3 +/- 0.2, 37.6 +/- 6.4, 45.3 +/- 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm(2). Limited apoptosis was observed in the medial wall (0.5 +/- 0.2, 8.5 +/- 4.7, 15.3 +/- 12.7%). Finally, Visudyne(r) PDT was found to be associated with reduced vessel functionality (Myogram). CONCLUSION: We demonstrated that sufficient accumulation of Visudyne(r) within plaque could be achieved in short-time and therefore validated the feasibility of local intravascular administration of photosensitizer. Intra-arterial Visudyne(r) PDT preferentially affected plaque macrophages and may therefore alter the dynamic progression of plaque development. PMID- 27672371 TI - The Semiology of Motor Disorders in Autism Spectrum Disorders as Highlighted from a Standardized Neuro-Psychomotor Assessment. AB - BACKGROUND: Altered motor performance has been described in Autism Spectrum Disorders (ASD) with disturbances in walking; posture, coordination, or arm movements, but some individuals with ASD show no impairment of motor skills. The neuro-developmental processes that underpin the performance of neuro-psychomotor functions have not been widely explored, nor is it clear whether there are neuro psychomotor functions specifically affected in ASD. Our objective was to focus on the semiology of motor disorders among children with ASD using a neuro developmental assessment tool. METHOD: Thirty-four children with ASD, with or without intellectual deficit (ID) were recruited in a child psychiatry department and Autism Resource Centers. Initial standard evaluations for diagnosis (psychiatric; psychological; psychomotor) were supplemented by a standardized assessment battery for neuro-developmental psychomotor functions (NP-MOT). RESULTS: The results of some NP-MOT tests differed between children with ASD with ID and those without. However, on the NP-MOT battery, neither of the two groups did well in the bi-manual and finger praxia tests (36 and 52% respectively failed). Manual and digital gnosopraxia showed some deficit (63 and 62% respectively failed). Postural deficits were found in tests for both static equilibrium (64%) and dynamic (52%). There were also difficulties in coordination between the upper and lower limbs in 58% of children. We found 75% failure in motor skills on the M-ABC test. Concerning muscular tone, significant laxity was observed in distal parts of the body (feet and hands), but hypertonia was observed in the proximal muscles of the lower limbs (reduced heel-ear angle). DISCUSSION: The results of manual and digital gnosopraxia tests point to a planning deficit in children with autism. A gesture programming deficit is also highlighted by the poor results in manual praxis, and by failures in the M-ABC tests despite prior training of the child. However, concerning global motor function, a significant difference was observed between children with and without ID. Our findings suggest a semiology of tone deregulation between proximal versus distal muscles, indeterminate tonic laterality, postural control deficit (proprioceptive), impairment of inter-hemispheric coordination (corpus callosum), and neurological soft signs such asdysdiadochokinesia, which leads us to hypothesize a general impairment of motor functions. PMID- 27672372 TI - Is Handwriting Performance Affected by the Writing Surface? Comparing Preschoolers', Second Graders', and Adults' Writing Performance on a Tablet vs. Paper. AB - Due to their multifunctionality, tablets offer tremendous advantages for research on handwriting dynamics or for interactive use of learning apps in schools. Further, the widespread use of tablet computers has had a great impact on handwriting in the current generation. But, is it advisable to teach how to write and to assess handwriting in pre- and primary schoolchildren on tablets rather than on paper? Since handwriting is not automatized before the age of 10 years, children's handwriting movements require graphomotor and visual feedback as well as permanent control of movement execution during handwriting. Modifications in writing conditions, for instance the smoother writing surface of a tablet, might influence handwriting performance in general and in particular those of non automatized beginning writers. In order to investigate how handwriting performance is affected by a difference in friction of the writing surface, we recruited three groups with varying levels of handwriting automaticity: 25 preschoolers, 27 second graders, and 25 adults. We administered three tasks measuring graphomotor abilities, visuomotor abilities, and handwriting performance (only second graders and adults). We evaluated two aspects of handwriting performance: the handwriting quality with a visual score and the handwriting dynamics using online handwriting measures [e.g., writing duration, writing velocity, strokes and number of inversions in velocity (NIV)]. In particular, NIVs which describe the number of velocity peaks during handwriting are directly related to the level of handwriting automaticity. In general, we found differences between writing on paper compared to the tablet. These differences were partly task-dependent. The comparison between tablet and paper revealed a faster writing velocity for all groups and all tasks on the tablet which indicates that all participants-even the experienced writers-were influenced by the lower friction of the tablet surface. Our results for the group comparison show advancing levels in handwriting automaticity from preschoolers to second graders to adults, which confirms that our method depicts handwriting performance in groups with varying degrees of handwriting automaticity. We conclude that the smoother tablet surface requires additional control of handwriting movements and therefore might present an additional challenge for learners of handwriting. PMID- 27672374 TI - Reference Point Heterogeneity. AB - It is well-established that, when confronted with a decision to be taken under risk, individuals use reference payoff levels as important inputs. The purpose of this paper is to study which reference points characterize decisions in a setting in which there are several plausible reference levels of payoff. We report an experiment, in which we investigate which of four potential reference points: (1) a population average payoff level, (2) the announced expected payoff of peers in a similar decision situation, (3) a historical average level of earnings that others have received in the same task, and (4) an announced anticipated individual payoff level, best describes decisions in a decontextualized risky decision making task. We find heterogeneity among individuals in the reference points they employ. The population average payoff level is the modal reference point, followed by experimenter's stated expectation of a participant's individual earnings, followed in turn by the average earnings of other participants in previous sessions of the same experiment. A sizeable share of individuals show multiple reference points simultaneously. The reference point that best fits the choices of the individual is not affected by a shock to her income. PMID- 27672373 TI - Remember Hard But Think Softly: Metaphorical Effects of Hardness/Softness on Cognitive Functions. AB - Previous studies have found that bodily stimulation, such as hardness biases social judgment and evaluation via metaphorical association; however, it remains unclear whether bodily stimulation also affects cognitive functions, such as memory and creativity. The current study used metaphorical associations between "hard" and "rigid" and between "soft" and "flexible" in Chinese, to investigate whether the experience of hardness affects cognitive functions whose performance depends prospectively on rigidity (memory) and flexibility (creativity). In Experiment 1, we found that Chinese-speaking participants performed better at recalling previously memorized words while sitting on a hard-surface stool (the hard condition) than a cushioned one (the soft condition). In Experiment 2, participants sitting on a cushioned stool outperformed those sitting on a hard surface stool on a Chinese riddle task, which required creative/flexible thinking, but not on an analogical reasoning task, which required both rigid and flexible thinking. The results suggest the hardness experience affects cognitive functions that are metaphorically associated with rigidity or flexibility. They support the embodiment proposition that cognitive functions and representations can be grounded in bodily states via metaphorical associations. PMID- 27672375 TI - The Measurement Invariance of the Student Opinion Scale across English and Non English Language Learner Students within the Context of Low- and High-Stakes Assessments. AB - Student effort on large-scale assessments has important implications on the interpretation and use of scores to guide decisions. Within the United States, English Language Learners (ELLs) generally are outperformed on large-scale assessments by non-ELLs, prompting research to examine factors associated with test performance. There is a gap in the literature regarding the test-taking motivation of ELLs compared to non-ELLs and whether existing measures have similar psychometric properties across groups. The Student Opinion Scale (SOS; Sundre, 2007) was designed to be administered after completion of a large-scale assessment to operationalize students' test-taking motivation. Based on data obtained on 5,257 (41.8% ELL) 10th grade students, study purpose was to test the measurement invariance of the SOS across ELLs and non-ELLs based on completion of low- and high-stakes assessments. Preliminary item analyses supported the removal of two SOS items (Items 3 and 7) that resulted in improved internal consistency for each of the two SOS subscales: Importance, Effort. A subsequent multi-sample confirmatory factor analysis (MCFA) supported the measurement invariance of the scale's two-factor model across language groups, indicating it met strict factorial invariance (Meredith, 1993). A follow-up latent means analysis found that ELLs had higher effort on both the low- and high-stakes assessment with a small effect size. Effect size estimates indicated negligible differences on the importance factor. Although the instrument can be expected to function similarly across diverse language groups, which may have direct utility of test users and research into factors associated with large-scale test performance, continued research is recommended. Implications for SOS use in applied and research settings are discussed. PMID- 27672376 TI - Empathic Accuracy and Observed Demand Behavior in Couples. PMID- 27672377 TI - Mindful Learning: A Case Study of Langerian Mindfulness in Schools. AB - The K-12 classroom applications of mindfulness as developed by Ellen Langer are discussed in a case study of a first-year charter school. Langerian Mindfulness, which is the act of drawing distinctions and noticing novelty, is deeply related to well-being and creativity, yet its impact has yet to be tested at the primary or secondary school level. The objective of the article is to display how Langerian Mindfulness strategies could increase 21st century skills and Social Emotional Learning in primary classrooms. The New School San Francisco, an inquiry-based, socioeconomically and racially integrated charter school, serves as a model for mindful teaching and learning strategies. It is concluded that when mindful strategies are implemented, students have significant opportunities to exercise the 21st century skills of creativity, collaboration, communication and critical thinking. Langerian Mindfulness is also considered as a tool for increasing Social-Emotional Learning in integrated classrooms. It is recommended that mindful interventions be further investigated in the primary and secondary school context. PMID- 27672378 TI - Does Side of Onset Influence the Pattern of Cerebral Atrophy in Parkinson's Disease? AB - BACKGROUND: Imaging studies have revealed widespread neurodegeneration in Parkinson's disease (PD), but only a few considered the issue of asymmetrical clinical presentations. OBJECTIVE: To investigate if the side of onset influences the pattern of gray matter (GM) atrophy in PD. METHODS: Sixty patients (57.87 +/- 10.27 years) diagnosed with idiopathic PD according to the U.K. Brain Bank criteria, 26 with right-sided disease onset (RDO) and 34 with left-sided disease onset (LDO), were compared to 80 healthy controls (HC) (57.1 +/- 9.47 years). We acquired T1-weighted images on a 3 T scanner. Images were processed and analyzed with VBM8 (SPM8/Dartel) on Matlab R2012b platform. Statistic assessments included a two-sample test (family-wise error p < 0.05) with extent threshold of 20 voxels. RESULTS: Compared to HC, LDO patients had GM atrophy in the insula, putamen, anterior cingulate, frontotemporal cortex, and right caudate, while the RDO group showed atrophy at the anterior cingulate, insula, frontotemporal, and occipital cortex. CONCLUSION: This study revealed widespread GM atrophy in PD, predominantly in the left hemisphere, regardless of the side of onset. Future investigations should also consider handedness and side of onset to better characterize cerebral involvement and its progression in PD. PMID- 27672380 TI - Occurence of ArmA and RmtB Aminoglycoside Resistance 16S rRNA Methylases in Extended-Spectrum beta-Lactamases Producing Escherichia coli in Algerian Hospitals. AB - The aim of this study, was to characterize the extended-spectrum-beta-lactamases (ESBLs) producing clinical strains of Escherichia coli isolated between January 2009 and June 2012 from Algerian hospitals and to determine the prevalence of 16S rRNA methylase among them. Sixty-seven ESBL-producers were detected among the 239 isolates included: 52 CTX-M-15-producers, 5 CTX-M-3-producers, 5 CTX-M-1 producers, 2 CTX-M-14-producers, 2 SHV-12-producers and one TEM-167-producer. Among the ESBL-producing strains twelve harbored 16S rRNA methylase genes: 8 rmtB and 4 armA. rmtB was located on a IncFIA plasmid and armA was located either on a IncL/M or a IncFIA plasmid. RmtB-producing isolates were genotypically related and belonged to the sequence type ST 405 whereas ArmA-producing isolates belonged to ST10, ST 167, and ST 117. This first description of 16S rRNA methylases among E. coli in Algerian hospitals pointed out the necessity to establish control measures to avoid their dissemination. PMID- 27672381 TI - Copy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens. AB - Pneumocystis jirovecii is an unculturable fungus and the causative agent of Pneumocystis pneumonia, a life-threatening opportunistic infection. Although molecular diagnosis is often based on the detection of mtLSU rRNA mitochondrial gene, the number of copies of mitochondrial genes had not been investigated. We developed and optimized six real-time PCR assays in order to determine the copy number of four mitochondrial genes (mtSSU rRNA, mtLSU rRNA, NAD1, and CYTB) in comparison to nuclear genome (DHPS and HSP70) and tested 84 bronchoalveolar fluids of patients at different stages of the infection. Unexpectedly, we found that copy number of mitochondrial genes varied from gene to gene with mtSSU rRNA gene being more represented (37 copies) than NAD1 (23 copies), mtLSU rRNA (15 copies) and CYTB (6 copies) genes compared to nuclear genome. Hierarchical clustering analysis (HCA) allowed us to define five major clusters, significantly associated with fungal load (p = 0.029), in which copy number of mitochondrial genes was significantly different among them. More importantly, copy number of mtLSU rRNA, NAD1, and CYTB but not mtSSU rRNA differed according to P. jirovecii physiological state with a decreased number of copies when the fungal load is low. This suggests the existence of a mixture of various subspecies of mtDNA that can harbor different amplification rates. Overall, we revealed here an unexpected variability of P. jirovecii mtDNA copy number that fluctuates according to P. jirovecii's physiological state, except for mtSSU that is the most stable and the most present mitochondrial gene. PMID- 27672382 TI - Arthrobacter sp. EpRS66 and Arthrobacter sp. EpRS71: Draft Genome Sequences from Two Bacteria Isolated from Echinacea purpurea Rhizospheric Soil. PMID- 27672379 TI - Protection by Neuroglobin Expression in Brain Pathologies. AB - Astrocytes play an important role in physiological, metabolic, and structural functions, and when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke, and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactate, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters, and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury, neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the central nervous system, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes. PMID- 27672383 TI - Aptamer-Based Technologies in Foodborne Pathogen Detection. AB - Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX); and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make the accurate assessments on the risks of infections (humans and animals) or contaminations (foods and other commodities) caused by various pathogens. This article reviews the development in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development in aptamer-based biosensors including optical biosensors for multiple pathogen detection by multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors and lateral chromatography test strips, and their applications in pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening remain to be overcome. PMID- 27672384 TI - Quantification of Growth of Campylobacter and Extended Spectrum beta-Lactamase Producing Bacteria Sheds Light on Black Box of Enrichment Procedures. AB - Campylobacter is well recognized as the leading cause of bacterial foodborne diarrheal disease worldwide, and is routinely found in meat originating from poultry, sheep, pigs, and cattle. Effective monitoring of Campylobacter contamination is dependent on the availability of reliable detection methods. The method of the International Organization for Standardization for the detection of Campylobacter spp. in food (ISO 10272-1:2006) recommends the use of Bolton broth (BB) as selective enrichment medium, including a pre-enrichment step of 4-6 h at 37 degrees C to revive sublethally damaged cells prior to incubation for 2 days at 41.5 degrees C. Recently the presence of abundantly growing extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL bacteria) has become one of the most important factors that interfere with the isolation of Campylobacter, resulting in false-negative detection. However, detailed growth dynamics of Campylobacter and its competitors remain unclear, where these would provide a solid base for further improvement of the enrichment procedure for Campylobacter. Other enrichment broths, such as Preston broth (PB) and BB plus clavulanic acid (BBc) have been suggested to inhibit competitive flora. Therefore, these different broths were used as enrichments to measure the growth kinetics of several strains of Campylobacter jejuni and ESBL bacteria separately, in co culture and of strains in chicken samples. The maximum cell numbers and often the growth rates of Campylobacter in mixed culture with ESBL bacteria were significantly lower than in single cultures, indicating severe suppression of Campylobacter by ESBL bacteria, also in naturally contaminated samples. PB and BBc successfully diminished ESBL bacteria and might therefore be a better choice as enrichment medium in possibly ESBL-bacteria contaminated samples. The efficacy of a pre-enrichment step in the BB ISO-procedure was not supported for cold stressed and non-stressed cells. Therefore, omission of this step (4-6 h at 37 degrees C) might be advised to obtain a less troublesome protocol. PMID- 27672386 TI - Release of Mannoproteins during Saccharomyces cerevisiae Autolysis Induced by Pulsed Electric Field. AB - The potential of the application of pulsed electric fields (PEF) to induce accelerate autolysis of a commercial strain of Saccharomyces cerevisiae for winemaking use was evaluated. The influence of PEF treatments of different intensity (5-25 kV/cm for 30-240 MUs) on cell viability, cytoplasmic membrane permeabilization and release of mannoproteins and compounds absorbing at 260 and 280 nm has been investigated. After 8 days of incubation at 25 degrees C the Abs600 of the suspension containing the control cells was kept constant while the Abs600 of the suspension containing the cells treated by PEF decreased. The measurement of the absorbance at 260 and 280 nm revealed no release of UV absorbing material from untreated cells after 8 days of incubation but the amount of UV absorbing material released drastically increased in the samples that contained cells treated by PEF after the same storage period. After 18 days of storage the amount of mannoproteins released from the untreated cell was negligible. Conversely, mannoprotein concentration increased linearly for the samples containing cells of S. cerevisiae treated by PEF. After 18 days of incubation the concentration of mannoproteins in the supernatant increased 4.2 times for the samples containing cells treated by PEF at 15 and 25 kV/cm for 45 and 150 MUs. Results obtained in this study indicates that PEF could be used in winemaking to accelerate the sur lie aging or to obtain mannoproteins from yeast cultures. PMID- 27672385 TI - Phytoplankton-Associated Bacterial Community Composition and Succession during Toxic Diatom Bloom and Non-Bloom Events. AB - Pseudo-nitzschia blooms often occur in coastal and open ocean environments, sometimes leading to the production of the neurotoxin domoic acid that can cause severe negative impacts to higher trophic levels. Increasing evidence suggests a close relationship between phytoplankton bloom and bacterial assemblages, however, the microbial composition and succession during a bloom process is unknown. Here, we investigate the bacterial assemblages before, during and after toxic and non-toxic Pseudo-nitzschia blooms to determine the patterns of bacterial succession in a natural bloom setting. Opportunistic sampling of bacterial community profiles were determined weekly at Santa Cruz Municipal Wharf by 454 pyrosequencing and analyzed together with domoic acid levels, phytoplankton community and biomass, nutrients and temperature. We asked if the bacterial communities are similar between bloom and non-bloom events and if domoic acid or the presence of toxic algal species acts as a driving force that can significantly structure phytoplankton-associated bacterial communities. We found that bacterial diversity generally increases when Pseudo-nitzschia numbers decline. Furthermore, bacterial diversity is higher when the low-DA producing P. fraudulenta dominates the algal bloom while bacterial diversity is lower when high-DA producing P. australis dominates the algal bloom, suggesting that the presence of algal toxin can structure bacterial community. We also found bloom related succession patterns among associated bacterial groups; Gamma proteobacteria, were dominant during low toxic P. fraudulenta blooms comprising mostly of Vibrio spp., which increased in relative abundance (6-65%) as the bloom progresses. On the other hand, Firmicutes bacteria comprising mostly of Planococcus spp. (12-86%) dominate during high toxic P. australis blooms, with the bacterial assemblage showing the same bloom-related successional patterns in three independent bloom events. Other environmental variables such as nitrate and phosphate and temperature appear to influence some low abundant bacterial groups as well. Our results suggest that phytoplankton-associated bacterial communities are strongly affected not just by phytoplankton bloom in general, but also by the type of algal species that dominates in the natural bloom. PMID- 27672387 TI - Nematode Peptides with Host-Directed Anti-inflammatory Activity Rescue Caenorhabditis elegans from a Burkholderia pseudomallei Infection. AB - Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs) have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi)-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8* MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators. PMID- 27672388 TI - UV-B Radiation Stress Causes Alterations in Whole Cell Protein Profile and Expression of Certain Genes in the Rice Phyllospheric Bacterium Enterobacter cloacae. AB - Among the different types of UV radiation, UV-B radiation (280-315 nm) has gained much attention mainly due to its increasing incidence on the Earth's surface leading to imbalances in natural ecosystems. This study deals with the effects of UV-B radiation on the proteome and gene expression in a rice phyllospheric bacterium, Enterobacter cloacae. Of the five bacteria isolated from rice leaves, E. cloacae showed the highest level of resistance to UV-B and total killing occurred after 8 h of continuous exposure to UV-B. Reactive oxygen species were induced by UV-B exposure and increased with increasing duration of exposure. Protein profiling by SDS-PAGE and 2-dimensional gel electrophoresis (2-DE) revealed major changes in the number as well as expression of proteins. Analysis of 2-DE gel spots indicated up/down-regulation of several proteins under the stress of UV-B radiation. Thirteen differentially expressed proteins including two hypothetical proteins were identified by MALDI-TOF MS and assigned to eight functional categories. Both the hypothetical proteins (gi 779821175 and gi 503938301) were over-expressed after UV-B irradiation; gi 503938301 was characterized as a member of FMN reductase superfamily whereas gi 779821175 seems to be a structural protein as it did not show any functional domain. That the expression of certain proteins under UV-B stress is indeed up-regulated was confirmed by qRT-PCR. Transcript analysis of selected gene including genes of hypothetical proteins (cp011650 and cp002886) showed over-expression under UV-B stress as compared to untreated control cultures. Although this study deals with a limited number of proteins, identification of differentially expressed proteins reported herein may prove useful in future studies especially for assessing their significance in the protection mechanism of bacteria against UV-B radiation stress. PMID- 27672390 TI - Editorial: Nanotoxicology and Environmental Risk Assessment of Engineered Nanomaterials (ENMs) in Plants. PMID- 27672389 TI - Hydrogen Peroxide and Polyamines Act as Double Edged Swords in Plant Abiotic Stress Responses. AB - The specific genetic changes through which plants adapt to the multitude of environmental stresses are possible because of the molecular regulations in the system. These intricate regulatory mechanisms once unveiled will surely raise interesting questions. Polyamines and hydrogen peroxide have been suggested to be important signaling molecules during biotic and abiotic stresses. Hydrogen peroxide plays a versatile role from orchestrating physiological processes to stress response. It helps to achieve acclimatization and tolerance to stress by coordinating intra-cellular and systemic signaling systems. Polyamines, on the other hand, are low molecular weight polycationic aliphatic amines, which have been implicated in various stress responses. It is quite interesting to note that both hydrogen peroxide and polyamines have a fine line of inter-relation between them since the catabolic pathways of the latter releases hydrogen peroxide. In this review we have tried to illustrate the roles and their multifaceted functions of these two important signaling molecules based on current literature. This review also highlights the fact that over accumulation of hydrogen peroxide and polyamines can be detrimental for plant cells leading to toxicity and pre mature cell death. PMID- 27672391 TI - Antiviral Therapy in Lamivudine-Resistant Chronic Hepatitis B Patients: A Systematic Review and Network Meta-Analysis. AB - The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical trials were searched in PUBMED, MEDLINE, EMBASE, and CNKI databases up to February 15, 2016. Nine trials including 764 patients met the entry criteria. In direct meta-analysis, TDF showed a stronger antiviral effect than any one of ETV, LAM/ADV, and ADV against LAM-R hepatitis B virus. LAM/ADV therapy was superior to ADV in suppressing viral replication. ETV achieved similar rate of HBV DNA undetectable compared to ADV or LAM/ADV. In network meta analysis, TDF had higher rates of HBV DNA undetectable compared to ETV (OR, 24.69; 95% CrI: 5.36-113.66), ADV (OR, 37.28; 95% CrI: 9.73-142.92), or LAM/ADV (OR, 21.05; 95% CrI: 5.70-77.80). However, among ETV, ADV, and LAM/ADV, no drug was clearly superior to others in HBV DNA undetectable rate. Moreover, no significant difference in the rate of ALT normalization or HBeAg loss was observed compared the four rescue strategies with each other. TDF appears to be a more effective rescue therapy than LAM/ADV, ETV, or ADV. LAM plus ADV therapy was a better treatment option than ETV or ADV alone for patients with LAM-R. PMID- 27672392 TI - In Vitro Antioxidant Treatment of Semen Samples in Assisted Reproductive Technology: Effects of Myo-Inositol on Nemaspermic Parameters. AB - Male infertility and the poor quality of sperm seem to be influenced by oxidative stress. In particular, the reactive oxygen species (ROS) mainly produced by morphologically altered spermatozoa affect sperm motility, morphology, and integrity. The aim of this study was to evaluate the efficacy of Myo-Inositol (Myo-Ins) on a number of parameters such as viscosity and total and progressive motility of spermatozoa, in order to better validate its possible practical application in vitro, in order to improve the capacitation protocols commonly used in Assisted Reproductive Technology (ART). A total of 100 fresh and 25 thawed semen samples were analyzed in vitro prior to and after addition of Myo Ins. Treatment of samples with Myo-Ins showed an increase in the sperm total and progressive motility in both fresh and thawed samples. Furthermore, Myo-Ins proved to be well tolerated by spermatozoa in vitro, demonstrating that it can be efficiently and safely used as antioxidant in the laboratory practice and for preparation of semen samples in ART. PMID- 27672393 TI - The Relationship between Adiposity and Insulin Sensitivity in African Women Living with the Polycystic Ovarian Syndrome: A Clamp Study. AB - Objectives. We aimed to assess the variation of insulin sensitivity in relation to obesity in women living with PCOS in a sub-Sahara African setting. Methods. We studied body composition, insulin sensitivity, and resting energy expenditure in 14 PCOS patients (6 obese and 8 nonobese) compared to 10 matched nonobese non PCOS subjects. Insulin sensitivity was assessed using the gold standard 80 mU/m(2)/min euglycemic-hyperinsulinemic clamp and resting energy expenditure was measured by indirect calorimetry. Results. Insulin sensitivity adjusted to lean mass was lowest in obese PCOS subjects and highest in healthy subjects (11.2 [10.1-12.4] versus 12.9 [12.1-13.8] versus 16.6 [13.8-17.9], p = 0.012); there was a tendency for resting energy expenditure adjusted for total body mass to decrease across the groups highest in obese PCOS subjects (1411 [1368-1613] versus 1274 [1174-1355] versus 1239 [1195-1454], p = 0.306). Conclusion. In this sub-Saharan population, insulin resistance is associated with PCOS per se but is further aggravated by obesity. Obesity did not seem to be explained by low resting energy expenditure suggesting that dietary intake may be a determinant of the obesity in this context. PMID- 27672395 TI - Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult. AB - Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP. PMID- 27672394 TI - Breast Cancer Prevalence and Mortality among Hispanic Subgroups in the United States, 2009-2013. AB - Background. This paper presents data on breast cancer prevalence and mortality among US Hispanics and Hispanic subgroups, including Cuban, Mexican, Puerto Rican, Central American, and South American. Methods. Five-year average annual female breast cancer prevalence and mortality rates for 2009-2013 were examined using data from the National Health Interview Survey (prevalence) and the National Center for Health Statistics and the American Community Survey (mortality rates). Results. Overall breast cancer prevalence among US Hispanic women was 1.03%. Although the estimates varied slightly by Hispanic subgroup, these differences were not statistically significant. The breast cancer mortality rate for Hispanics overall was 17.71 per 100,000 women. Higher rates were observed among Cubans (17.89), Mexicans (18.78), and Puerto Ricans (19.04), and a lower rate was observed among Central and South Americans (10.15). With the exception of the rate for Cubans, all Hispanic subgroup rates were statistically significantly different from the overall Hispanic rate. Additionally, all Hispanic subgroups rates were statistically significantly higher than the Central and South American rate. Conclusion. The data reveal significant differences in mortality across Hispanic subgroups. These data enable public health officials to develop targeted interventions to help lower breast cancer mortality among the highest risk populations. PMID- 27672396 TI - The Current State of Cell Therapies for Cerebrovascular Diseases. PMID- 27672399 TI - Acute and Subacute Toxicological Evaluation of the Aerial Extract of Monsonia angustifolia E. Mey. ex. A. Rich in Wistar Rats. AB - The acute and subacute toxicity profile of the aerial extract of Monsonia angustifolia in Wistar rats was evaluated. The Organization for Economic Cooperation and Development (OECD) 420 guideline was adopted in the acute toxicity testing with a single oral dose of 5000 mg/kg (b.w.). For the 28-day daily oral dosing, the extract was administered at 75, 150, and 300 mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single dose of 5000 mg/kg b.w. the extract elicited no treatment-related signs of toxicity in the animals during the 14 days of experimental period. In the subacute toxicity, there was no significant difference in hematological, renal, and liver function indices. However, dose-dependent significant increases were observed on the plasma concentrations of white blood cell and platelet counts of the treated animals compared to the control group. While cage observations revealed no treatment facilitated signs of toxicity, histopathological examinations of the kidneys and liver also showed no obvious lesions and morphological changes. These results suggest that the extract may be labelled and classified as safe and practically nontoxic within the doses and period of investigation in this study. PMID- 27672398 TI - Self-Administered Mind-Body Practices for Reducing Health Disparities: An Interprofessional Opinion and Call to Action. AB - Health disparities (HD) continue to persist in the United States which underscores the importance of using low-cost, accessible, evidence-based strategies that can improve health outcomes, especially for chronic conditions that are prevalent among underserved minority populations. Complementary/integrative health modalities, particularly self-administered mind body practices (MBP), can be extremely useful in reducing HD because they are intrinsically patient-centered and they empower patients to actively engage in self-care of health and self-management of symptoms. Interprofessional healthcare providers and patients can engage in powerful partnerships that encompass self administered MBP to improve health. This is a call to action for interprofessional researchers to engage in high-quality research regarding efficacy and cost-effectiveness of self-administered MBP, for practitioners to engage patients in self-administered MBP for health promotion, disease prevention, and symptom management, and for healthcare institutions to integrate self-administered MBP into conventional health practices to reduce HD in their communities. PMID- 27672397 TI - Effects of Brazilian Propolis on Dental Plaque and Gingiva in Patients with Oral Cleft Malformation Treated with Multibracket and Removable Appliances: A Comparative Study. AB - Orthodontic appliances modify the local environment of the oral cavity, increase the accumulation of dental plaque, and affect the condition of the gingiva. The aim of this study is assessment of Brazilian propolis toothpaste's effect on plaque index (PLI) and gingival index (GI) in patients with CL/CLP treated using orthodontic appliances in the 35-day study period. The study population included 96 patients of an Orthodontic Outpatient Clinic, ACSiMS in Bytom. All the patients participated in the active phase of orthodontic treatment using buccal multibracket appliances or removable appliances. During the first examination, each patient was randomly qualified to the propolis group or control group. A statistically significant decrease in GI and PLI in the entire propolis group (P < 0.01) was shown during repeated examination. Insignificant change in GI was in the entire control group during the repeated examination compared to the baseline. Similar result was obtained in patients treated with multibracket and removable appliances. The orthodontic appliance type did not affect the final dental plaque amount and gingival condition in patients using the propolis toothpaste. These results may be clinically useful to improve prevention and control oral infectious diseases during orthodontic treatment patients with oral cleft. PMID- 27672400 TI - Effect of Tongxinluo on Podocyte Apoptosis via Inhibition of Oxidative Stress and P38 Pathway in Diabetic Rats. AB - Diabetic nephropathy (DN) has been the leading cause of end-stage renal disease (ESRD). Podocyte apoptosis is a main mechanism of progression of DN. It has been demonstrated that activated P38 and caspase-3 induced by oxidative stress mainly account for increased podocyte apoptosis and proteinuria in DN. Meanwhile, Tongxinluo (TXL) can ameliorate renal structure disruption and dysfunction in DN patients in our clinical practice. However, the effect of TXL on podocyte apoptosis and P38 pathway remains unclear. To explore the effect of TXL on podocyte apoptosis and its molecular mechanism in DN, our in vivo and in vitro studies were performed. TXL attenuated oxidative stress in podocyte in DN in our in vivo and in vitro studies. Moreover, TXL inhibited the activation of P38 and caspase-3. Bcl-2 and Bax expression was partially restored by TXL treatment in our in vivo and in vitro studies. More importantly, TXL decreased podocyte apoptosis in diabetic rats and high glucose cultured podocyte. In conclusion, TXL protects podocyte from apoptosis in DN, partially through its antioxidant effect and inhibiting of the activation of P38 and caspase-3. PMID- 27672401 TI - Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance. AB - Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP) rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP) expression in dorsal root ganglion (DRG). Methods. Forty SD rats were divided into five groups: sham, CIBP (B), CIBP + morphine (BM), CIBP + electroacupuncture (BE), and CIBP + morphine + electroacupuncture (BME). B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9). Mechanical withdraw threshold (MWT) was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P < 0.01). From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5). From M5 to M9, BME had the differences with BM group (P < 0.01). IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P < 0.01). Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors. PMID- 27672403 TI - Dietary broccoli protects against fatty liver development but not against progression of liver cancer in mice pretreated with diethylnitrosamine. AB - Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months. Dietary broccoli decreased hepatic triacylglycerols, NAFLD, liver damage and tumour necrosis factor by month 5 without changing body weight or relative liver weight, but did not slow carcinogenesis, seen in 100% of mice. We conclude that broccoli, a good source of sulforaphane, slows progression of hepatic lipidosis, but not tumourigenesis in this robust model. PMID- 27672402 TI - Determinants of Smoking and Cessation Among Latinos: Challenges and Implications for Research. AB - Tobacco is a significant burden to individual and public health, and disparities exist among Latino smokers with respect to use and cessation. Although the prevalence of smoking is lower for Latinos than for non-Latino Whites and the general U.S. population, numerous health disparities exist within the population of Latino smokers. Much is known about determinants of smoking and cessation but the vast majority of this knowledge is based on research with non-Latino White smokers. This results in at least two important challenges in tobacco research among Latino smokers: (i) demonstrating the generalizability of known determinants of smoking and cessation, and; (ii) identifying culturally relevant variables that influence smoking and cessation among Latinos. An argument for increased research in these areas is presented with a review of existing research among Latino smokers that demonstrates these needs. Research is summarized that suggests socioeconomic position, depressive symptomatology, physical dependence, and gender function differently as determinants of smoking and cessation among Latinos compared with the general population of smokers. Research is also reviewed that suggests the promise of acculturation, acculturative stress, and discrimination as culturally relevant determinants of smoking and cessation. Research and practice implications are discussed, and specific areas for future research are offered. PMID- 27672405 TI - Whole Genome Sequence Analysis of an Alachlor and Endosulfan Degrading Micrococcus sp. strain 2385 Isolated from Ochlockonee River, Florida. AB - We recently isolated Micrococcus sp. strain 2385 from Ochlockonee River, Florida and demonstrated potent biodegradative activity against two commonly used pesticides- alachlor [(2-chloro-2',6'-diethylphenyl-N (methoxymethyl)acetanilide)] and endosulfan [(6,7,8,9,10,10-hexachloro 1,5,5a,6,9,9a-hexahydro-6,9methano-2,3,4-benzo(e)di-oxathiepin-3-oxide], respectively. To further identify the repertoire of metabolic functions possessed by strain 2385, a draft genome sequence was obtained, assembled, annotated and analyzed. The genome sequence of Micrococcus sp. strain 2385 consisted of 1,460,461,440 bases which assembled into 175 contigs with an N50 contig length of 50,109 bases and a coverage of 600x. The genome size of this strain was estimated at 2,431,226 base pairs with a G+C content of 72.8 and a total number of 2,268 putative genes. RAST annotated a total of 340 subsystems in the genome of strain 2385 along with the presence of 2,177 coding sequences. A genome wide survey indicated that that strain 2385 harbors a plethora of genes to degrade other pollutants including caprolactam, PAHs (such as naphthalene), styrene, toluene and several chloroaromatic compounds. PMID- 27672404 TI - De novo Assembly and Analysis of the Chilean Pencil Catfish Trichomycterus areolatus Transcriptome. AB - Trichomycterus areolatus is an endemic species of pencil catfish that inhabits the riffles and rapids of many freshwater ecosystems of Chile. Despite its unique adaptation to Chile's high gradient watersheds and therefore potential application in the investigation of ecosystem integrity and environmental contamination, relatively little is known regarding the molecular biology of this environmental sentinel. Here, we detail the assembly of the Trichomycterus areolatus transcriptome, a molecular resource for the study of this organism and its molecular response to the environment. RNA-Seq reads were obtained by next generation sequencing with an Illumina(r) platform and processed using PRINSEQ. The transcriptome assembly was performed using TRINITY assembler. Transcriptome validation was performed by functional characterization with KOG, KEGG, and GO analyses. Additionally, differential expression analysis highlights sex-specific expression patterns, and a list of endocrine and oxidative stress related transcripts are included. PMID- 27672406 TI - Turbo-SMT: Parallel Coupled Sparse Matrix-Tensor Factorizations and Applications. AB - How can we correlate the neural activity in the human brain as it responds to typed words, with properties of these terms (like 'edible', 'fits in hand')? In short, we want to find latent variables, that jointly explain both the brain activity, as well as the behavioral responses. This is one of many settings of the Coupled Matrix-Tensor Factorization (CMTF) problem. Can we enhance any CMTF solver, so that it can operate on potentially very large datasets that may not fit in main memory? We introduce Turbo-SMT, a meta-method capable of doing exactly that: it boosts the performance of any CMTF algorithm, produces sparse and interpretable solutions, and parallelizes any CMTF algorithm, producing sparse and interpretable solutions (up to 65 fold). Additionally, we improve upon ALS, the work-horse algorithm for CMTF, with respect to efficiency and robustness to missing values. We apply Turbo-SMT to BrainQ, a dataset consisting of a (nouns, brain voxels, human subjects) tensor and a (nouns, properties) matrix, with coupling along the nouns dimension. Turbo-SMT is able to find meaningful latent variables, as well as to predict brain activity with competitive accuracy. Finally, we demonstrate the generality of Turbo-SMT, by applying it on a Facebook dataset (users, 'friends', wall-postings); there, Turbo-SMT spots spammer-like anomalies. PMID- 27672407 TI - Molecular Insights into Fully Human and Humanized Monoclonal Antibodies: What are the Differences and Should Dermatologists Care? AB - In recent years, a large number of therapeutic monoclonal antibodies have come to market to treat a variety of conditions including patients with immune-mediated chronic inflammation. Distinguishing the relative clinical efficacy and safety profiles of one monoclonal antibody relative to another can be difficult and complex due to different clinical designs and paucity of head-to-head comparator studies. One distinguishing feature in interpreting clinical trial data by dermatologists may begin by determining whether a monoclonal antibody is fully human or humanized, which can be discerned by the generic name of the drug. Herein, this commentary highlights the distinctions and similarities of fully human and humanized monoclonal antibodies in their nomenclature, engineering, and clinical profiles. While there are a number of differences between these types of monoclonal antibodies, current evidence indicates that this designation does not impart any measurable impact on overall clinical efficacy and safety profiles of a given drug. Based on molecular insights provided in this commentary, it is clear that each monoclonal antibody, irrespective of being fully human or humanized, should be individually assessed for its clinical impact regarding safety and efficacy. Going beyond the type of generic name ascribed to a monoclonal antibody will be an ever-increasing theme for dermatologists as more therapeutic monoclonal antibodies emerge to potentially treat a wider scope of diseases with cutaneous manifestations. PMID- 27672408 TI - An Investigator-initiated Study to Assess the Safety and Efficacy of Ingenol Mebutate 0.05% Gel When Used After Cryosurgery in the Treatment of Hypertrophic Actinic Keratosis on Dorsal Hands. AB - OBJECTIVES: To evaluate the safety and efficacy of ingenol mebutate 0.05% gel after cryosurgery versus cryosurgery alone for the treatment of hypertrophic and nonhypertrophic actinic keratosis on the dorsal hands. DESIGN: Investigator blinded split arm study. SETTING: Academic institution. PARTICIPANTS: Sixteen subjects with actinic keratoses on dorsal hands. RESULTS: There was a mean reduction in the number of hypertrophic actinic keratosis lesions adjusted for baseline in ingenol mebutate-treated versus control group of -4.3 versus -2.8, respectively. There was a mean reduction in the number of non-hypertrophic actinic keratosis lesions in the ingenol mebutate-treated versus control group of -3.8 versus -0.3. CONCLUSION: A statistically significant and clinically meaningful difference in response was demonstrated in favor of ingenol mebutate treated hands versus controls. No significant increase in local skin responses was noted when applying ingenol mebutate 0.05% gel on the same day as cryosurgery. TRIAL REGISTRY: ClinicalTrials.gov, NCT02251652. PMID- 27672409 TI - Improving Treatment of Erythematotelangiectatic Rosacea with Laser and/or Topical Therapy Through Enhanced Discrimination of its Clinical Features. AB - Rosacea is a chronic inflammatory disease that can present with a variety of cutaneous symptoms. Erythematotelangiectatic rosacea is a subtype characterized by flushing (transient erythema), persistent central facial erythema (background erythema), and telangiectasias. The severity of individual symptoms differs in each patient, which can complicate the selection of an appropriate treatment strategy. Evaluation of these specific symptoms has been greatly improved by the routine use of diagnostic tools such as (video) dermatoscopy. Following a thorough clinical assessment, treatment decisions should be made based on the proportion of these individual symptoms in individual patients. Brimonidine 0.33% gel is recommended in the symptomatic treatment of facial erythema, and there is evidence for the efficacy of laser/light-based therapies in the treatment of erythema and telangiectasias. In patients presenting with both marked background erythema and telangiectasias, initial treatment with brimonidine 0.33% gel to target the erythema followed by laser/light-based therapy for the telangiectasias has been shown to be an effective combination in clinical practice. This article aims to facilitate treatment decision-making in clinical practice through: 1) better differentiation of the main symptoms of erythematotelangiectatic rosacea and 2) practical advice for the selection of appropriate treatments, based on clinical case examples. PMID- 27672410 TI - A Comprehensive Critique and Review of Published Measures of Acne Severity. AB - OBJECTIVE: Acne vulgaris is a dynamic, complex condition that is notoriously difficult to evaluate. The authors set out to critically evaluate currently available measures of acne severity, particularly in terms of suitability for use in clinical trials. DESIGN: A systematic review was conducted to identify methods used to measure acne severity, using MEDLINE, CINAHL, Scopus, and Wiley Online. Each method was critically reviewed and given a score out of 13 based on eight quality criteria under two broad groupings of psychometric testing and suitability for research and evaluation. RESULTS: Twenty-four methods for assessing acne severity were identified. Four scales received a quality score of zero, and 11 scored <=3. The highest rated scales achieved a total score of 6. Six scales reported strong inter-rater reliability (ICC>0.75), and four reported strong intra-rater reliability (ICC>0.75). The poor overall performance of most scales, largely characterized by the absence of reliability testing or evidence for independent assessment and validation indicates that generally, their application in clinical trials is not supported. CONCLUSION: This review and appraisal of instruments for measuring acne severity supports previously identified concerns regarding the quality of published measures. It highlights the need for a valid and reliable acne severity scale, especially for use in research and evaluation. The ideal scale would demonstrate adequate validation and reliability and be easily implemented for third-party analysis. The development of such a scale is critical to interpreting results of trials and facilitating the pooling of results for systematic reviews and meta-analyses. PMID- 27672411 TI - Enhancement of International Dermatologists' Pigmented Skin Lesion Biopsy Decisions Following Dermoscopy with Subsequent Integration of Multispectral Digital Skin Lesion Analysis. AB - BACKGROUND: Early detection and subsequent management of melanoma are critical for patient survival. New technologies have been developed to augment clinician analysis of suspicious pigmented skin lesions. OBJECTIVE: To determine how information provided by a multispectral digital skin lesion analysis device affects the biopsy decisions of international dermatologists following clinical and dermoscopic pigmented skin lesion evaluation. METHODS: Participants at a dermoscopy conference in Vienna, Austria, were shown 12 clinical and dermoscopic images of pigmented skin lesions (2 melanomas in situ, 3 invasive melanomas, and 7 low-grade dysplastic nevi) previously analyzed by multispectral digital skin lesion analysis. Participants were asked if they would biopsy the lesion based on clinical images, again after observing high-resolution dermoscopy images, and again when subsequently shown multispectral digital skin lesion analysis information. RESULTS: Data were analyzed from a total of 70 international dermatologists. Overall, sensitivity was 58 percent after clinical evaluation (C) and 59 percent post-dermoscopy (D), but 74 percent after multispectral digital skin lesion analysis. Participant specificity was 56 percent (C) decreasing to 51 percent (D), but increasing to 61 percent with multispectral digital skin lesion analysis. Diagnostic accuracy was 57 percent (C) decreasing to 54 percent (D), but increasing to 67 percent for dermatologists after integrating the multispectral digital skin lesion analysis data into the biopsy decision. The overall number of lesions biopsied increased from 50 percent (C) to 53 percent (D), rising to 54 percent after multispectral digital skin lesion analysis. CONCLUSION: Decisions to biopsy melanocytic lesions were more sensitive and specific when multispectral digital skin lesion analysis information was provided with no significant increase in the number of biopsies recommended. Providing multispectral digital skin lesion analysis data may lead to additional improvement in biopsy accuracy with a concomitant decrease in the number of nonessential biopsies for pigmented skin lesions even after dermoscopic evaluation. PMID- 27672412 TI - Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review. AB - Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID- 27672413 TI - Results of a Phase 2 Efficacy and Safety Study with SB204, an Investigational Topical Nitric Oxide-releasing Drug for the Treatment of Acne Vulgaris. AB - OBJECTIVE: To compare efficacy, tolerability, and safety of two concentrations of topical SB204 and vehicle twice daily for 12 weeks in the treatment of acne vulgaris. DESIGN: Randomized, double-blind, placebo-controlled, three-arm, Phase 2 study. SETTING: Dominican Republic, Panama, and Honduras. PARTICIPANTS: Subjects with acne, age 12 to 40, with 25 to 70 noninflammatory lesions, 20 to 40 inflammatory lesions, and a baseline Investigator's Global Assessment score of mild, moderate, or severe. MEASUREMENTS: The primary efficacy assessment was the absolute change in noninflammatory lesion counts. Other assessments included inflammatory lesion counts, success on dichotomized Investigator's Global Assessment, reported adverse events, physical examinations, laboratory testing, and tolerability. RESULTS: One hundred fifty-three subjects were randomized to vehicle (n=52), SB204 1% (n=51), or SB204 4% (n=50). When compared to vehicle, subjects treated with SB204 1% and SB204 4% had significantly greater mean percent reduction in noninflammatory lesions from baseline and subjects treated with SB204 4% had a significantly greater mean percent reduction in inflammatory lesion count from baseline at Week 12. There were no significant differences in the IGA success rates between groups. Both concentrations of SB204 were safe and well-tolerated. CONCLUSIONS: When compared to vehicle, both SB204 1% and SB204 4% significantly decreased the percentage of noninflammatory lesions and SB204 4% also significantly decreased the percentage of inflammatory lesions in subjects with acne vulgaris treated for 12 weeks. Treatment with SB204 1% and SB204 4% was safe and well-tolerated. Registry: clinicaltrials.gov (NCT01844752). PMID- 27672414 TI - Gender Differences in Self-assessed Health-related Quality of Life in Children with Atopic Dermatitis. AB - BACKGROUND: Atopic dermatitis has a significant impact on quality of life of children and families. OBJECTIVE: It is important to assess gender differences in health-related quality of life in children with atopic dermatitis in order to effectively use health-related quality of life results. METHODS: Children 5- to 16-years of age with atopic dermatitis from Italy, Singapore, Czech Republic, and Ukraine were divided into two groups (boys and girls). Each child in the group of boys was matched to a corresponding child in the group of girls from the same country whose age and scoring atopic dermatitis value were almost identical. Self assessed health-related quality of life was measured by the Children's Dermatology Life Quality Index. RESULTS: The difference in overall Children's Dermatology Life Quality Index between boys and girls was not significant (P=0.33). Girls with atopic dermatitis assessed Children's Dermatology Life Quality Index item on embarrassment significantly higher (0.78+/-0.93 for boys and 1.14+/-0.93 for girls, P<0.05). Lowest scored items were the same and overall Children's Dermatology Life Quality Index results significantly correlated with scoring atopic dermatitis values in both groups. Two separate Children's Dermatology Life Quality Index items in boys and five items in girls significantly correlated with atopic dermatitis severity. The Children's Dermatology Life Quality Index item on affected sleep significantly correlated with the age of boys (r=0.38, P=0.02) and another Children's Dermatology Life Quality Index item on school work/holiday with the age of girls (r=0.59, P<0.01). CONCLUSION: Despite that the authors did not find differences in overall health related quality of life results, girls were more embarrassed, self-conscious, upset, and sad because of atopic dermatitis. The authors' results may influence the educational part of consultations of children with atopic dermatitis. PMID- 27672415 TI - New Oral Therapies for Psoriasis: A Comprehensive Review. AB - Conventional oral therapies for psoriasis, including methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-standing use. Thus, new oral therapies are necessary for patients with more moderate disease, patients who prefer oral treatments to injectable biologies, and patients who failed conventional therapies. The authors review here the clinical and safety evidence of phosphodiesterase 4 inhibitor, apremilast, janus kinase inhibitors, including tofacitinib, and fumarie acid esters as additional options in oral psoriasis therapy. PMID- 27672416 TI - Application of Nail Polish During Topical Management of Onychomycosis: Are Data Available to Guide the Clinician About What to Tell Their Patients? AB - Topical antifungal management of toenail onychomycosis has been fraught with several therapeutic challenges including difficulty gaining access to the site of infection and the need for prolonged durations of therapy. In addition, there has been a marked lack of information on the impact of toenail polish application on drug penetration after application. This article reviews available data from studies evaluating the effect of nail polish on antifungal drag penetration using ex vivo laboratory models with cadaver fingernail plates with both tavaborole 5% solution and efinaconazole 10% solution. In addition, changes in nail polish appearance and color transfer to applicators are also discussed, with changes noted with topical efinaconazole. Importantly, there are no data on whether or not nail polish application alters the efficacy of these topical agents. PMID- 27672417 TI - The Use of Noninvasive Optical Coherence Tomography to Monitor the Treatment Progress of Vismodegib and Imiquimod 5% Cream in a Transplant Patient with Advanced Basal Cell Carcinoma of the Nose. AB - Immunosuppressed transplant recipients have increased risk for the development of basal cell carcinoma skin cancers. While oral vismodegib therapy has been successful in treating locally advanced basal cell tumors, few studies document its use and efficacy in organ transplant patients. In this immunocompromised population, topical imiquimod 5% cream has been shown to be an effective and well tolerated option for superficial and nodular basal cell carcinomas. To the authors' knowledge, no data documents the use of optical coherence tomography, a noninvasive imaging technique, to monitor progress of such combined therapies on in vivo skin. The authors report the successful treatment of an extensive basal cell carcinoma on the nose of an immunosuppressed 54-year-old Caucasian man with a history of kidney and pancreas transplantations. By combining continuous noninvasive lesion monitoring with vismodegib 150mg/d therapy and adjuvant imiquimod 5% topical cream, the patient showed complete disease clearance on clinical, optical coherence tomography, and histological evaluation. This report supports the feasibility and efficacy of nonsurgical treatment of basal cell lesions in complicated transplant patients and the need for individualized treatment plans. A noninvasive follow-up tool, especially during nonsurgical therapy, is of critical value to ensure the best possible treatment outcome for the patient. PMID- 27672418 TI - Fully Regressive Melanoma: A Case Without Metastasis. AB - Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID- 27672419 TI - Central Forehead Reconstruction with a Simple Primary Vertical Linear Closure. AB - OBJECTIVE: Following Mohs surgery, medium-to-large defects on the central forehead can often be complicated to surgically reconstruct. In this paper, the authors discuss possible central forehead reconstructions and report their successful experience employing a simple primary vertical linear closure with a special technique to demarcate forehead rhytides rather than performing an overly complicated flap or graft. CASE REPORT: The patient was a 57-year-old man who presented with a broad superficial basal cell carcinoma that required treatment with Mohs surgery. For the resulting defect, the authors elected to perform a complex linear repair taking advantage of substantial side-to-side laxity in the supraperiosteal plane and carefully labeling and matching each forehead rhytide across the defect as the wound was sutured. CONCLUSION: The findings of this case demonstrate that medium-to-large wounds of the central forehead can be aesthetically repaired with a simple primary vertical linear closure. Carefully mapping and labeling horizontal forehead rhytides with a sterile surgical marking pen prior to anesthesia ensures accurate approximation during wound closure. PMID- 27672420 TI - Modulatory Effect of 2-(4-Hydroxyphenyl)amino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta. AB - The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4 naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10-3 M), an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10-2 M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8 M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation. PMID- 27672421 TI - Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives. AB - Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response. PMID- 27672422 TI - Role of targeted therapy in metastatic colorectal cancer. AB - Colorectal cancer (CRC) is a significant cause of cancer-related morbidity and mortality all over the world. Improvements of cytotoxic and biologic agents have prolonged the survival in metastatic CRC (mCRC), with a median overall survival of approximately 2 years and more in the past two decades. The biologic agents that have proven clinical benefits in mCRC mainly target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). In particular, bevacizumab targeting VEGF and cetuximab and panitumumab targeting EGFR have demonstrated significant survival benefits in combination with cytotoxic chemotherapy in the first-line, second-line, or salvage setting. Aflibercept, ramucirumab, and regorafenib are also used in second-line or salvage therapy. Recent retrospective analyses have shown that KRAS or NRAS mutations were negative predictive markers for anti-EGFR therapy. Based on the evidence from large randomized clinical trials, personalized therapy is necessary for patients with mCRC according to their tumor biology and characteristics. The aim of this paper was to summarize the results of the major randomized clinical trials and highlight the benefits of the molecular targeted agents in patients with mCRC. PMID- 27672424 TI - Pathogenesis and risk factors for gastric cancer after Helicobacter pylori eradication. AB - Helicobacter pylori (H. pylori) infection was thought to be the main cause of gastric cancer, and its eradication showed improvement in gastric inflammation and decreased the risk of gastric cancer. Recently, a number of studies reported the occurrence of gastric cancer after successful eradication. Patients infected with H. pylori, even after eradication, have a higher risk for the occurrence of gastric cancer when compared with uninfected patients. Metachronous gastric cancer occurs frequently following the endoscopic removal of early gastric cancer. These data indicate that metachronous cancer leads to the occurrence of gastric cancer even after successful eradication of H. pylori. The pathogenesis of this metachronous cancer remains unclear. Further research is needed to identify biomarkers to predict the development of metachronous gastric cancer and methods for gastric cancer screening. In this article, we review the role of the H. pylori in carcinogenesis and the histological and endoscopic characteristics and risk factors for metachronous gastric cancer after eradication. Additionally, we discuss recent risk predictions and possible approaches for reducing the risk of metachronous gastric cancer after eradication. PMID- 27672423 TI - Role of the preoperative usefulness of the pathological diagnosis of pancreatic diseases. AB - Pancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is currently capable of providing a cytopathological diagnosis of pancreatic malignancies with a higher diagnostic power, with a sensitivity and specificity of 85%-89% and 98%-99%, compared to pancreatic juice cytology (PJC), whose sensitivity and specificity are only 33.3%-93% and 83.3% 100%. However, EUS-FNA is not effective in the cases of carcinoma in situ and minimally invasive carcinoma because both are undetectable by endoscopic ultrasonography, although PJC is able to detect them. As for the frequency of complications such as post endoscopic retrograde cholangiopancreatography pancreatitis, EUS-FNA is safer than PJC. To diagnose pancreatic cancer appropriately, it is necessary for us to master both procedures so that we can select the best methods of sampling tissues while considering the patient's safety and condition. PMID- 27672426 TI - Pancreatic cancer: New hopes after first line treatment. AB - Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Extensive research has yielded advances in first-line treatment strategies, but there is no standardized second-line therapy. In this review, we examine the literature trying to establish a possible therapeutic algorithm. PMID- 27672425 TI - Molecular mechanisms of chemoresistance in gastric cancer. AB - Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness of chemotherapy, which results in treatment failure. Resistance to chemotherapy can be present intrinsically before the administration of chemotherapy or it can develop during chemotherapy. The mechanisms of chemotherapy resistance in gastric cancer are complex and multifactorial. A variety of factors have been demonstrated to be involved in chemoresistance, including the reduced intracellular concentrations of drugs, alterations in drug targets, the dysregulation of cell survival and death signaling pathways, and interactions between cancer cells and the tumor microenvironment. This review focuses on the molecular mechanisms of chemoresistance in gastric cancer and on recent studies that have sought to overcome the underlying mechanisms of chemoresistance. PMID- 27672427 TI - Association between serum vitamin D levels and gastric cancer: A retrospective chart analysis. AB - AIM: To determine whether there is an increased risk of gastric adenocarcinoma associated with vitamin D deficiency (VDd). METHODS: A retrospective case control study was performed of all patients diagnosed with gastric adenocarcinoma between 2005 and 2015. After we excluded the patients without a documented vitamin D level, 49 patients were included in our study. RESULTS: The average age of patients with gastric adenocarcinoma and documented vitamin D level was 64 years old (95%CI: 27-86) and average vitamin D level was 20.8 mg/dL (95%CI: 4-44). Compared to a matched control group, the prevalence of VDd/insufficiency in patients with gastric adenocarcinoma was significantly higher than normal vitamin D levels (83.7% vs 16.3%). Forty-one patients (83.7%) with adenocarcinoma showed VDd/insufficiency compared to 18 (37%) patients with normal vitamin D level without gastric cancer (OR: 8.8, 95%CI: 5-22, P value < 0.0001). The average age of males with gastric adenocarcinoma diagnosis was 60 years old vs 68 years old for females (P = 0.01). Stage II gastric adenocarcinoma was the most prevalent in our study (37%). CONCLUSION: We reported a positive relationship between VDd and gastric adenocarcinoma, that is to say, patients with decreased VDd levels have an increased propensity for gastric adenocarcinoma. PMID- 27672428 TI - Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer. AB - AIM: To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer. METHODS: We evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Sisli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and >= 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed. RESULTS: When the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median +/- SD) of groups showed a significant difference of as 5 +/- 1.28 wk in group I and 10.1 +/- 2.2 wk in group II (P < 0.001). The median follow up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79). CONCLUSION: Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response. PMID- 27672429 TI - Questionnaire survey regarding the current status of super-extended lymph node dissection in Japan. AB - AIM: To verify the current status of super-extended lymph node dissection for advanced gastric cancer according to a questionnaire survey. METHODS: One-hundred and five institutions responded to the questionnaire. The survey included the following items: Number of experiences, whether performed prophylactically and/or therapeutically, whether preoperative chemotherapy was provided, number of preoperative chemotherapy rounds, and therapeutic options after chemotherapy. RESULTS: Eighty-seven of the 105 institutions (83%) had performed D3 gastrectomy in the past or continued to perform D3 gastrectomy at present. However, D3 gastrectomy was rarely performed prophylactically in clinical practice. Seventy eight institutions (74%) indicated that preoperative chemotherapy with curative intent was required for patients suspected of having para-aortic node (PAN) metastases. After chemotherapy, a D3 gastrectomy was scheduled for patients with a complete or partial response, stable disease, and progressive disease at 36 (46%), 28 (36%), and 13 (17%) of the institutions, respectively. CONCLUSION: For patients with apparent PAN metastasis, a D3 gastrectomy is typically planned if a few courses of preoperative chemotherapy yield at least a stable disease condition. PMID- 27672430 TI - Comparison of nutritional intake in US adolescent swimmers and non-athletes. AB - Swimming is a very popular sport among adolescents in the US. Little is known about the diet of competitive adolescent swimmers in the US but data from other countries indicate several inadequacies, including excessive intake of fat and lower than recommended intake of carbohydrate and several micronutrients that may affect athletic performance and bone accrual. We assessed usual diet, using a food frequency questionnaire and calcium checklist, among 191 adolescent males and females [91 swimmers (mean 13.7, s = 2.5 years) and 100 non-athletes (mean 14.4, s = 2.8 years)]. For both males and females, swimmers and non-athletes generally had similar average intakes of macro- and micro-nutrients, including higher than recommended amounts of total fat (36%) and saturated fat (12%), and inadequate amounts of calcium, vitamin D, and daily servings of fruits, vegetables, grains, and dairy products. This first study of nutritional intake among adolescent swimmers in the US suggests that dietary habits of adolescents who swim competitively may jeopardize optimal athletic performance and place them at risk for future chronic diseases, including osteoporosis. PMID- 27672431 TI - Short-term adjusted outcomes for heart failure. AB - PURPOSE: Heart failure (HF) is recognized as a major problem in industrialized countries. Short-term adjusted outcomes are indicators of quality for care process during/after hospitalization. Our aim is to evaluate, for patients with principal diagnosis of HF, in-hospital mortality and 30-day readmissions for all causes using two different risk adjustment (RA) tools. METHODS AND RESULTS: We used data from the hospital discharge abstract (HD) of a retrospective cohort of patients (2002-2007) admitted in Tuscan hospitals, Italy. Considered outcomes were in-hospital mortality and readmission at 30 days. We compared the All Patients Refined Diagnosis Related Groups (APR-DRG) system and the Elixhauser Index (EI). Logistic regression was performed and models were compared using the C statistic (C). examined records were 58.202. Crude in-hospital mortality was 9.7%. Thirty-day readmission was 5.1%. The APR-DRG class of risk of death (ROD) was a predictive factor for in-hospital mortality; the APR-DRG class of severity was not significantly associated with 30-day readmissions (P>0.05). EI comorbidities which were more strongly associated with outcomes were nonmetastatic cancer for in-hospital mortality (odds ratio, OR 2.25, P<0.001), uncomplicated and complicated diabetes for 30-day hospital readmissions (OR 1.20 and 1.34, P<0.001). The discriminative abilities for in-hospital mortality were sufficient for both models (C 0.67 for EI, C 0.72 for APR-DRG) while they were low for 30-day readmissions rate (C 0.53 and 0.52). CONCLUSIONS: Age, gender, APR DRG ROD and some Elixhauser comorbidities are predictive factors of outcomes; only the APR-DRG showed an acceptable ability to predict hospital mortality while none of them was satisfactory in predicting the readmissions within 30 days. PMID- 27672432 TI - Yield of contemporary clinical strategies to detect patients with obstructive coronary artery disease. AB - PURPOSE: Noninvasive ischemia testing (NIST) is recommended for most patients suspected to have stable coronary artery disease (CAD) before invasive coronary angiography (ICA). We sought to assess the diagnostic predictive ability of NIST over clinical risk profiling in a contemporary sample of patients undergoing the currently recommended diagnostic triage strategy. METHODS: From 2006 to 2011, 2,600 consecutive patients without known CAD undergoing elective ICA in a single tertiary-care center were retrospectively identified and the prevalence of obstructive CAD determined. To understand the incremental value of frequently used clinical parameters in predicting obstructive CAD, receiver operating characteristic curves were plotted for six sequential models starting with Framingham risk score and then progressively adding multiple clinical factors and finally NIST results. RESULTS: At ICA 1,268 patients (48.8%) had obstructive CAD. The vast majority (85%) were classified in an intermediate clinical pretest probability of CAD and NIST prior to ICA was used in 86% of the cohort. The most powerful correlate of obstructive CAD was the presence of severe angina (odds ratio (OR) = 9.1; 95% confidence interval (CI) 4.3-19.1). Accordingly, the incorporation of NIST in a sequential model had no significant effect on the predictive ability over that achieved by clinical and symptomatic status model (C statistic 0.754; 95% CI 0.732-0.776, p = 0.28). CONCLUSIONS: Less than half the patients with suspect stable obstructive CAD referred to a tertiary-level center for elective ICA had the diagnosis confirmed. In this clinical setting, the results of NIST may not have the power to change the discriminative ability over clinical judgment alone. PMID- 27672433 TI - Effectiveness of the CardioPain initiative in reducing inappropriate NSAID prescriptions in pain therapy among high cardiovascular risk patients: an informative Italian survey. AB - AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (COXIBs) may be associated with increased cardiovascular (CV) risk and mortality in CV patients. After the release of Note 66 by Agenzia Italiana del Farmaco (AIFA) to reduce inappropriate prescribing of NSAIDs and COXIBs, the CARDIOPAIN initiative was started in Italy to include such recommendations into the hospital discharge letter of patients with high CV risk. We evaluated the effect of the CARDIOPAIN initiative on the prescription of analgesic drugs by general practitioners (GPs). METHODS: An online interview was proposed to 414 Italian GPs. A descriptive statistic was reported. RESULTS: Three groups of GPs were identified: those who found the Note 66 recommendations in most hospital discharge letters (the "MOST" group), those who found them in only few cases (the "FEW" group) and those who never found the recommendations (the "NO" group). In patients with high CV risk, the percentage of GPs prescribing NSAIDs as first choice in pain management was lower in the MOST group compared with the "FEW" or "NO" groups. GPs belonging to the "MOST" group prescribed NSAIDs in 28% of cases, compared with 50% of cases observed for GPs belonging to the "NO" group. The more severe the pathology the fewer the NSAID prescriptions, in favor of opioid agents administration. CONCLUSIONS: Our results suggest that the inclusion of the AIFA Note 66 in the discharge documents of high CV risk patients may have contributed to lower inappropriate NSAID prescriptions in Italian GPs. Presumably, a wider diffusion of the CARDIOPAIN initiative might improve the prescription appropriateness of analgesic drugs. PMID- 27672434 TI - Aspiration thrombectomy in a case of acute myocardial infarction due to coronary emboli in a patient with peripartum cardiomyopathy and mural thrombus. AB - Acute coronary syndrome (ACS) due to embolic phenomenon in the setting of peripartum cardiomyopathy (PPCM) and left ventricular mural thrombus is a rare occurrence. There have been two known cases described in medical literature. We present a unique case in which catheter-based aspiration thrombectomy was used to successfully treat a patient with ACS due to coronary emboli in the setting of PPCMand left ventricular mural thrombus. We believe this to be the first report of the use of aspiration thrombectomy in such a clinical case. PMID- 27672435 TI - Differences in coronary artery blood velocities in the setting of normal coronary angiography and normal stress echocardiography. AB - BACKGROUND: Normal left anterior descending (LAD) coronary artery as determined by coronary angiography is considered not only to reflect normal angiography but also to correlate with normal anatomy and function. However, subjects who undergo coronary angiography may differ from those who do not need to have invasive evaluation even if their functional noninvasive studies like dobutamine stress echocardiography (DSE) were normal. AIM: LAD velocities in subjects with normal angiography and those with normal DSE are equal. METHODS: A total of 244 subjects were evaluated, 78 had normal LAD by angiography and 166 had normal LAD by DSE. All had Doppler sampling of LAD velocities by transthoracic echocardiography. RESULTS: Velocity was higher in the angiographic subgroup in diastole 41 +/- 23 vs 33 +/- 14 cm/s, p = 0.0078; systole 18 +/- 14 vs 13 +/- 7 cm/s, p = 0.012; diastolic integral 12.6 +/- 5 vs 9.8 +/- 3.8 cm, p = 3.15 * 10(-5); systolic velocity integral 4 +/- 2.9 vs 2.8 +/- 1.9, p = 0.0014. While heart rate was similar in both groups, the product of diastolic velocity integral and heart rate of the LAD in the angiographic group was higher: 902 +/- 450 vs 656 +/- 394, p = 0.00599. Diastolic velocity deceleration time was similar in both groups. Coronary flow reserve defined as diastolic velocity ratio before and immediately after DSE correlated negatively with baseline velocity, r = -0.4. CONCLUSIONS: Mode of defining normality of coronary artery affects velocity behavior of the vessel, reflecting functional differences possibly related to microvasculature and vasodilatation. PMID- 27672438 TI - Treatment of postoperative sciatic nerve palsy after total hip arthroplasty for postoperative acetabular fracture: A case report. AB - Acetabular fracture is usually treated with osteosynthesis. However, in the case of an intra-articular fracture, osteosynthesis can result in arthropathy of the hip joint and poor long-term results, hence, total hip arthroplasty is required. However, in total hip arthroplasty for postoperative acetabular fracture, sciatic nerve palsy tends to develop more commonly than after primary total hip arthroplasty. This is a case report of a 57-year-old Japanese male who had internal skeletal fixation for a left acetabular fracture that had occurred 2 years earlier. One year later, he developed coxarthrosis and severe pain of the hip joint and total hip arthroplasty was performed. After the second surgery, he experienced pain along the distribution of the sciatic nerve and weakness of the muscles innervated by the peroneal nerve, indicating sciatic nerve palsy. We performed a third operation, and divided adhesions around the sciatic nerve. Postoperatively, the anterior hip joint pain and the buttocks pain when the hip was flexed were improved. Abduction of the fifth toe was also improved. However, the footdrop and sensory disturbance were not improved. A year after the third operation, sensory disturbance was slightly improved but the footdrop was not improved. We believe the sciatic nerve palsy developed when we dislocated the hip joint as the sciatic nerve was excessively extended as the hip joint flexed and internally rotated. Sciatic nerve adhesion can occur easily in total hip replacement for postoperative acetabular fracture; hence, adhesiotomy should be conducted before performing hip dislocation to prevent injury caused by nerve tension. The patient agreed that the details of this case could be submitted for publication. The work has been reported in line with the CARE criteria and cite. PMID- 27672437 TI - Preparation and characterization of photoactive antimicrobial graphitic carbon nitride (g-C3N4) films. AB - Photoactive films derived from nanostructured samples of metal-free, intermediate band gap semiconductor graphitic carbon nitride (ns-g-C3N4) have been synthesized and characterized for their particle properties and antimicrobial activity. Physical characterization reveals that these materials are composed of discrete nanoparticles whose dimensions range from 200 nm to 700 nm. Investigation of the photochemical reactivity of ns-g-C3N4 using coumarin-3-carboxylic acid (3-CCA) indicates that this material produces reactive oxygen species (ROS) under visible radiation. When irradiated with 0.31J visible light, ns-g-C3N4-based materials reduced the viability of both gram-negative Escherichia coli O157:H7 and gram positive Staphylococcus aureus by approximately 50%. Nearly complete inactivation of both strains of microorganisms was achieved upon administration of a 0.62J dose of visible radiation. Importantly, no biocidal activity was observed for non irradiated samples, indicating that the g-C3N4-derived films are not inherently toxic in the absence of visible light. The results of this study suggest that materials and, by extention, films and coatings derived from g-C3N4 may present a novel route for controlling pathogenic microorganisms on surfaces in the environment, and could be useful in reducing incidents of hospital-acquired infections. PMID- 27672439 TI - Zinner's syndrome: report of two cases and review of the literature. AB - BACKGROUND: Congenital malformations of the seminal vesicle are uncommon, and most of them are cystic malformations. If an insult occurs between the 4th and the 13 h gestational week, the embryogenesis of the kidney, ureter, seminal vesicle, and vas deferens could be altered. Cysts of the seminal vesicle may appear with a mass effect, dysuria, epididymitis, or obstruction of the gastrointestinal and genitourinary tracts. Approximately two thirds of them are associated with ipsilateral renal agenesis, because both the ureteral buds and seminal vesicles originate from the mesonephric (Wolffian) duct. They were first described by Zinner in 1914, and 200 cases of seminal vesicle cysts associated with ipsilateral renal agenesis have been reported in the literature. Most patients with this anomaly are asymptomatic until the third or fourth decade of life. Some cases have nonspecific symptoms such as prostatism, urinary urgency, dysuria, painful ejaculation, and perineal discomfort. Transrectal ultrasonography provides good visualization of the pelvic structures and allows guidance for aspiration of the cysts. CASE PRESENTATION: We present two cases of seminal vesicle cyst. The first patient had dysuria, increased frequency of urination, and haematuria. He was operated and benefited from a removal of the cyst with right ureterectomy and left ureteral reimplantation. The second patient had disorder of the digestive transit and he benefited from a laparoscopic removal of the cyst. CONCLUSIONS: Seminal vesicle cysts combined with ipsilateral renal agenesis are rare urological anomalies. Usual symptoms that are caused by the seminal vesicle cysts are bladder irritation and obstruction as well as pain in the perineum and scrotum. Epididymitis is frequently found. Treatment consists to removing the seminal vesicle cyst. PMID- 27672436 TI - SLC Transporters: Structure, Function, and Drug Discovery. AB - The human Solute Carrier (SLC) transporters are important targets for drug development. Structure-based drug discovery for SLC transporters requires the description of their structure, dynamics, and mechanism of interaction with small molecule ligands and ions. The recent determination of atomic structures of human SLC transporters and their homologs, combined with improved computational power and prediction methods have led to an increased applicability of structure-based drug design methods for human SLC members. In this review, we provide an overview of the SLC transporters' structures and transport mechanisms. We then describe computational techniques, such as homology modeling and virtual screening that are emerging as key tools to discover chemical probes for human SLC members. We illustrate the utility of these methods by presenting case studies in which rational integration of computation and experiment was used to characterize SLC members that transport key nutrients and metabolites, including the amino acid transporters LAT-1 and ASCT2, the SLC13 family of citric acid cycle intermediate transporters, and the glucose transporter GLUT1. We conclude with a brief discussion about future directions in structure-based drug discovery for the human SLC superfamily, one of the most structurally and functionally diverse protein families in human. PMID- 27672440 TI - Retraction Note: Brain injury following cardiac arrest: pathophysiology for neurocritical care. AB - [This retracts the article DOI: 10.1186/s40560-016-0140-9.]. PMID- 27672441 TI - Hepatic steatosis, detected by hepatorenal index in ultrasonography, as a predictor of insulin resistance in obese subjects. AB - BACKGROUND: The metabolic syndrome is a worldwide health issue, with non alcoholic fatty liver disease (liver steatosis) being one of its features, particularly closely related to insulin resistance. This study aims to investigate whether quantification of hepatic steatosis by abdominal ultrasonography, using hepatorenal index, is a feasible tool for the prediction of insulin resistance, and thus the metabolic syndrome. METHODS: Patients were recruited from the Centre of Obesity at the University Hospital of North Norway, and among participants from the Sixth Tromso Study. Homeostasis Model Assessment of Insulin Resistance (HOMA1-IR) was measured, body mass index (BMI, kg/m(2)) calculated, and hepatorenal index (HRI), i.e. the ratio of liver to kidney optical densities, was measured by transabdominal ultrasonography. Receiver operating characteristic (ROC) analyses were performed, detecting insulin resistance at HOMA1-IR cut-off values >2.3 and >2.5. RESULTS: Ninety participants were included in the study, of which 46 (51 %) had BMI >=30 and 27 (30 %) had BMI >=35. Overall, HRI at level 1.17 had sensitivity 0.90 and specificity 0.70 for predicting insulin resistance (HOMA1-IR >2.3) in all participants. For participants with BMI >=30, HRI at level 1.17 had sensitivity 0.94 and specificity 0.70, and for BMI >=35, HRI at level 1.17 had sensitivity 0.93 and specificity 0.75 for predicting HOMA1-IR >2.3. Setting the HRI limit at 1.42 gave low sensitivities and high specificities in all BMI groups. In the analysis predicting HOMA1-IR >2.5, sensitivity values were almost the same as in the analysis predicting HOMA1-IR >2.3, but specificity values were lower in this analysis. CONCLUSION: Detection and quantification of hepatic steatosis by ultrasound and the hepatorenal index is a feasible screening tool for identifying patients with low risk of having insulin resistance (IR, HRI <1.17), patients at risk of having IR (HRI 1.17-1.41) and patients with likely IR (HRI >=1.42), especially in obese individuals. PMID- 27672442 TI - Moving toward a prevention strategy for osteoporosis by giving a voice to a silent disease. AB - A major unmet challenge in developing preventative treatment programs for osteoporosis is that the optimal timing of treatment remains unknown. In this commentary we make the argument that the menopausal transition (MT) is a critical period in a woman's life for bone health, and that efforts aimed at reducing fracture risk later in life may benefit greatly from strategies that treat women earlier with the intent of keeping bones strong as long as possible. Bone strength is an important parameter to monitor during the MT because engineering principles can be applied to differentiate those women that maintain bone strength from those women that lose bone strength and are in need of early treatment. It is critical to understand the underlying mechanistic causes for reduced strength to inform treatment strategies. Combining measures of strength with data on how bone structure changes during the MT may help differentiate whether a woman is losing strength because of excessive bone resorption, insufficient compensatory bone formation, trabeculae loss, or some combination of these factors. Each of these biomechanical mechanisms may require a different treatment strategy to keep bones strong. The technologies that enable physicians to differentially diagnose and treat women in a preventive manner, however, have lagged behind the development of prophylactic treatments for osteoporosis. To take advantage of these treatment options, advances in preventive treatment strategies for osteoporosis may require developing new technologies with imaging resolutions that match the pace by which bone changes during the MT and supplementing a woman's bone mineral density (BMD)-status with information from engineering-based analyses that reveal the structural and material changes responsible for the decline in bone strength during the menopausal transition. PMID- 27672443 TI - Pharmaceutical studies on and clinical application of olanzapine suppositories prepared as a hospital preparation. AB - BACKGROUND: A new formulation of olanzapine available for terminally ill patients is needed. Rectal administration using suppositories is an alternative for patients for whom administration via the oral route is not feasible. In the present study, we prepared olanzapine suppositories, and confirmed using pharmaceutical tests. Furthermore, we demonstrated the efficacy and safety of olanzapine suppositories in terminally ill patients. METHODS: We prepared olanzapine suppositories using bases consisting of different compositions of Witepsol H-15, Witepsol S-55, and Witepsol E-75. The suppository release test was performed, and the olanzapine suppository with the best dissolution rate was selected. The suppository was assessed using the content uniformity test, content test in suppositories, hardness test, stability test, and clinical efficacy and safety. RESULTS: The dissolution rate at 360 min of olanzapine suppositories with Witepsol H-15 was the best (77.0 +/- 3.3 %). The suppositories prepared had a uniform weight (2.47 +/- 0.02 g) and content (2.11 +/- 0.07 mg). The power required to break suppositories was 7.96 +/- 0.55 kgf. When olanzapine suppositories were stored with protection from light, their contents were maintained regardless of whether the temperature was at 4 degrees C or room temperature. The numbers of patients administered 2.5 mg, 5 mg, and 10 mg of olanzapine suppositories were 4, 19, and 1. The percentages of patients with delirium or nausea and vomiting cured with olanzapine suppositories were 82 and 57 %, respectively. CONCLUSION: We suggest that olanzapine suppositories prepared in the hospital by pharmacists will improve the quality of life of terminally ill patients. TRIAL REGISTRATION: UMIN000022172. May 2, 2016 retrospectively registered. PMID- 27672445 TI - Erratum: Nuclear localization of platelet-activating factor receptor controls retinal neovascularization. AB - [This corrects the article DOI: 10.1038/celldisc.2016.17.]. PMID- 27672444 TI - NTRK2 activation cooperates with PTEN deficiency in T-ALL through activation of both the PI3K-AKT and JAK-STAT3 pathways. AB - Loss of PTEN, a negative regulator of the phosphoinositide 3-kinase signaling pathway, is a frequent event in T-cell acute lymphoblastic leukemia, suggesting the importance of phosphoinositide 3-kinase activity in this disease. Indeed, hyperactivation of the phosphoinositide 3-kinase pathway is associated with the disease aggressiveness, poor prognosis and resistance to current therapies. To identify a molecular pathway capable of cooperating with PTEN deficiency to drive oncogenic transformation of leukocytes, we performed an unbiased transformation screen with a library of tyrosine kinases. We found that activation of NTRK2 is able to confer a full growth phenotype of Ba/F3 cells in an IL3-independent manner in the PTEN-null setting. NTRK2 activation cooperates with PTEN deficiency through engaging both phosphoinositide3-kinase/AKT and JAK/STAT3 pathway activation in leukocytes. Notably, pharmacological inhibition demonstrated that p110alpha and p110delta are the major isoforms mediating the phosphoinositide 3 kinase/AKT signaling driven by NTRK2 activation in PTEN-deficient leukemia cells. Furthermore, combined inhibition of phosphoinositide 3-kinase and STAT3 significantly suppressed proliferation of PTEN-mutant T-cell acute lymphoblastic leukemia both in culture and in mouse xenografts. Together, our data suggest that a unique conjunction of PTEN deficiency and NTRK2 activation in T-cell acute lymphoblastic leukemia, and combined pharmacologic inhibition of phosphoinositide 3-kinase and STAT3 signaling may serve as an effective and durable therapeutic strategy for T-cell acute lymphoblastic leukemia. PMID- 27672446 TI - In Vivo Positional Analysis of Implantable Collamer Lens Using Ultrasound Biomicroscopy. AB - Purpose. To evaluate the anterior segment, the anatomical position of the implantable collamer lenses (ICL), and its relationship to adjacent ocular structures using Ultrasound Biomicroscopy (UBM). Methods. In a prospective study, 142 myopic eyes of 93 patients implanted with Visian ICL were subjected to UBM examination between March 2010 and January 2015. The relative position of ICL to the adjacent structure and the overall iris configuration were evaluated. The machine calibers were used to measure the minimum central distance between the ICL and anterior lens capsule (vault) and the vertical central distance between the corneal endothelium and the ICL (E-ICL). Results. The mean ICL vault was 376 +/- 105 MUm. The mean E-ICL was 2826 +/- 331 MUm. Contact between ICL and the posterior epithelium of the iris was present in all eyes. The overall iris configuration was flat in 89 eyes. Central anterior convexity was present in 41 eyes and mild peripheral iris bombe in 12 eyes. The haptics could be imaged in the ciliary sulcus in 112 eyes and at least one haptic resting on the lens periphery and zonules in 30 eyes. Conclusion. UBM can provide valuable anatomical information that allows detailed postoperative in vivo assessment of ICL. PMID- 27672447 TI - Corneal Epithelial Remodeling and Its Effect on Corneal Asphericity after Transepithelial Photorefractive Keratectomy for Myopia. AB - Purpose. To evaluate the changes in epithelial thickness profile following transepithelial photorefractive keratectomy (T-PRK) for myopia and to investigate the effect of epithelial remodeling on corneal asphericity. Methods. Forty-four patients (44 right eyes) who underwent T-PRK were retrospectively evaluated. Epithelial thickness was measured using spectral-domain optical coherence tomography at different corneal zones (central, 2 mm; paracentral, 2-5 mm; and mid-peripheral, 5-6 mm) preoperatively and at 1 week and 1, 3, and 6 months postoperatively. The correlation between the changes in corneal epithelial thickness (DeltaCET) and postoperative Q-value changes (DeltaQ) was analyzed 6 months postoperatively. Results. Epithelial thickness at 6 months showed a negative meniscus-like lenticular pattern with less central thickening, which increased progressively toward the mid-periphery (3.69 +/- 4.2, 5.19 +/- 3.8, and 6.23 +/- 3.9 MUm at the center, paracenter, and mid-periphery, resp., P < 0.01). A significant positive relationship was observed between epithelial thickening and DeltaQ 6 months postoperatively (r = 0.438, 0.580, and 0.504, resp., P < 0.01). Conclusions. Significant epithelial thickening was observed after T-PRK and showed a lenticular change with more thickening mid-peripherally, resulting in increased oblateness postoperatively. Epithelial remodeling may modify the epithelial thickness profile after surface ablation refractive surgery for myopia. PMID- 27672448 TI - RMP: Reduced-set matching pursuit approach for efficient compressed sensing signal reconstruction. AB - Compressed sensing enables the acquisition of sparse signals at a rate that is much lower than the Nyquist rate. Compressed sensing initially adopted [Formula: see text] minimization for signal reconstruction which is computationally expensive. Several greedy recovery algorithms have been recently proposed for signal reconstruction at a lower computational complexity compared to the optimal [Formula: see text] minimization, while maintaining a good reconstruction accuracy. In this paper, the Reduced-set Matching Pursuit (RMP) greedy recovery algorithm is proposed for compressed sensing. Unlike existing approaches which either select too many or too few values per iteration, RMP aims at selecting the most sufficient number of correlation values per iteration, which improves both the reconstruction time and error. Furthermore, RMP prunes the estimated signal, and hence, excludes the incorrectly selected values. The RMP algorithm achieves a higher reconstruction accuracy at a significantly low computational complexity compared to existing greedy recovery algorithms. It is even superior to [Formula: see text] minimization in terms of the normalized time-error product, a new metric introduced to measure the trade-off between the reconstruction time and error. RMP superior performance is illustrated with both noiseless and noisy samples. PMID- 27672449 TI - Mechanochemical synthesis of chitosan submicron particles from the gladius of Todarodes pacificus. AB - The present work focused on the synthesis of beta-chitosan submicron particles (CSPs) from Todarodes pacificus using mechanochemical techniques. The gladius was submitted to a sequence of mechanical and chemical treatments to synthesize beta chitin (CT), which was further deacetylated to form spherical chitosan submicron particles with an average diameter of ?100 nm. The surface morphology of beta chitin and CSPs was observed using electron microscopy. The degree of deacetylation (DD%), evaluated from the absorbance peak of a Fourier Transform Infrared (FTIR) spectrum, was 80 +/- 2.5%. Physicochemical characterization exhibited good crystallinity, positive zeta potential and low molecular weight, as well as reduced ash content and high water-binding capacity. CSPs exhibit significant antimicrobial properties toward all tested pathogenic bacterial and fungal microorganisms. Antioxidant analysis revealed high reducing power and excellent scavenging and chelating ability. Hence, CSPs synthesized from gladius of Todarodes pacificus using mechanochemical techniques are promising candidates for biomedical applications. PMID- 27672450 TI - A review on bis-hydrazonoyl halides: Recent advances in their synthesis and their diverse synthetic applications leading to bis-heterocycles of biological interest. AB - This review covers a summary of the literature data published on the chemistry of bis-hydrazonoyl halides over the last four decades. The biological activities of some of the bis-heterocyclic compounds obtained from these bis-hydrazonoyl halides are also reviewed and discussed. PMID- 27672451 TI - Perceptions and Experiences about Self-Disclosure of HIV Status among Adolescents with Perinatal Acquired HIV in Poor-Resourced Communities in South Africa. AB - Background. There is limited research on the disclosure experiences of adolescents with perinatal acquired HIV (PAH). The study explores how adolescents with PAH experience living with HIV and examined their perceptions and experiences regarding disclosure and onward self-disclosure to friends and sexual partners. Methods. Thematic analysis was used to analyze in-depth interviews conducted with 37 adolescents. Findings. Adolescents received disclosure about their status at mean age of 12 years. They perceived disclosure as necessary and appreciated the truthful communication they received. Adolescents have learned to accept and live with HIV, and they desired to be healthy and normal like other people. After receiving disclosure, they found their treatment meaningful, and they adhered to medication. However, they also expressed a strong message that their HIV status was truly their secret and that self-disclosure to others will take the feeling of being normal away from them because they will be treated differently. Conclusion. Adolescents maintained secrecy in order to be accepted by their peers but also to protect themselves from stigma and isolation. Given that adolescents want to be informed of their HIV status but desire controlling self-disclosure of their HIV status, these should form the basis for development of disclosure interventions. PMID- 27672452 TI - An Exploratory Study Using Cortisol to Describe the Response of Incarcerated Women IPV Survivors to MAMBRA Intervention. AB - Objective. To determine if incarcerated women survivors of IPV had a physiological response to the Music and Account-Making for Behavioral-Related Adaptation (MAMBRA) intervention, as measured by cortisol levels. Methods. A single-group repeated measures designed exploratory study was used to pilot-test MAMBRA. A convenience sample (n = 33) was recruited in a Midwestern women's correctional facility. Serving as their own control, participants provided demographics and pre-/post-MAMBRA salivary samples while attending four MAMBRA sessions. Baseline data were compared to participants' data collected over the remaining 3 MAMBRA sessions. Data were analyzed with descriptive and univariate statistics with an alpha of .05 and post-hoc power of .65. Results. Participants were predominantly White (52%), single (80%), and early middle-aged ([Formula: see text]), with a history of physical/nonphysical spousal abuse. Using a subsample (n = 26), salivary cortisol decreased between the pre-/post-MAMBRA over the sessions (F(3,75) = 4.59, p < .01). Conclusion. Participants had a physiological response to the MAMBRA intervention as evidenced by the decreased cortisol between the pre-/post-MAMBRA. This is the first step in examining MAMBRA's clinical utility as an intervention for female IPV survivors. Future longitudinal studies will examine MAMBRA's effectiveness given this change in cortisol. PMID- 27672453 TI - Short-Term Effects of Hydrokinesiotherapy in Hospitalized Preterm Newborns. AB - Background. In the neonatal intensive care unit (NICU) environment, preterm newborns are subject to environmental stress and numerous painful interventions. It is known that hydrokinesiotherapy promotes comfort and reduces stress because of the physiological properties of water. Objective. To evaluate the short-term effects of hydrokinesiotherapy on reducing stress in preterm newborns admitted to the NICU. Materials and Methods. Fifteen preterm newborns underwent salivary cortisol measurement, pain evaluation using the Neonatal Infant Pain Scale (NIPS), and heart rate, respiratory rate, and peripheral oxygen saturation measurements before and after the application of hydrokinesiotherapy. Results. The mean gestational age of the newborns was 34.2 +/- 1.66 weeks, and the mean weight was 1823.3 +/- 437.4 g. Immediately after application of hydrokinesiotherapy, a significant reduction was observed in salivary cortisol (p = 0.004), heart rate (p = 0.003), and respiratory rate (p = 0.004) and a significant increase was observed in peripheral oxygen saturation (p = 0.002). However, no significant difference was observed in the NIPS score (p > 0.05). Conclusion. In the present study, neonatal hydrotherapy promoted short-term relief from feelings of stress. Neonatal hydrokinesiotherapy may be a therapeutic alternative. However, this therapy needs to be studied in randomized, crossover, and blinded trials. This trial is registered with NCT02707731. PMID- 27672454 TI - Bronchoesophageal Fistula Stenting Using High-Frequency Jet Ventilation and Underwater Seal Gastrostomy Tube Drainage. AB - Managing a patient scheduled for bronchoesophageal fistula repair is challenging for the anesthetist. If appropriate ventilation strategy is not employed, serious complications such as hypoxemia, gastric distension, and pulmonary aspiration can occur. We present the case of a 62-year-old man with a bronchoesophageal fistula in the left main stem bronchus requiring the insertion of a Y-shaped tracheobronchial stent through a rigid bronchoscope, under general anesthesia. We successfully managed this intervention and herein report this case to demonstrate the effectiveness of underwater seal gastrostomy tube drainage used in conjunction with high-frequency jet ventilation during bronchoesophageal fistula stenting. PMID- 27672455 TI - Successful Intravascular Ultrasound-Guided Transradial Coronary Intervention with a 4Fr Guiding Catheter. AB - Minimizing the catheter size can reduce vascular access complications and contrast dye usage in coronary angiography. The small diameter of the 4Fr guiding catheter has limited the use of several angioplasty devices such as intravascular ultrasound (IVUS) in the past. However, the combination of a novel IVUS catheter and a 0.010 guidewire makes it possible to perform IVUS-guided percutaneous coronary intervention (PCI) with a 4Fr guiding catheter. We herein report the case of a 51-year-old man with silent myocardial ischemia who underwent IVUS guided transradial PCI with a 4Fr guiding catheter. PMID- 27672456 TI - Reversal of a Suspected Paradoxical Reaction to Zopiclone with Flumazenil. AB - We describe the care for an elderly woman who was admitted to the intensive care unit (ICU) to receive noninvasive ventilation for acute exacerbation of chronic obstructive pulmonary disease. After administration of the sleeping pill zopiclone, a nonbenzodiazepine receptor agonist (NBRA), the patient became agitated and was confused, a possible paradoxical reaction to benzodiazepines. These symptoms were immediately resolved after treatment with flumazenil, usually used to reverse the adverse effects of benzodiazepines or NBRAs and to reverse paradoxical reactions to benzodiazepines. This case indicates that zopiclone induced behavioral changes resembling a paradoxical reaction to benzodiazepines and these symptoms may be treated with flumazenil. PMID- 27672457 TI - Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone. AB - Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form. PMID- 27672458 TI - Root Canal Stripping: Malpractice or Common Procedural Accident-An Ethical Dilemma in Endodontics. AB - Root canal stripping is defined as an oblong, vertical perforation that appears especially in the middle section of curved root canals during endodontic treatments with nickel-titanium (Ni-Ti) instruments. Its occurrence may drastically affect the outcome of the treatment, transforming a common otherwise efficient endodontic procedure into a complication such as tooth extraction. In order to discuss the ethical and legal consequences, two cases of dental strip perforations are herewith presented. Due to the existence of risk factors for dental strip perforation, experience of the clinician and the use of magnification and modern imagistic methods (CBCT) may avoid or reduce the frequency of this type of accidents. Under correct working circumstances, dental stripping should not be regarded as a malpractice but as a procedural accident. However, the patient must always be informed, before and during the endodontic procedure, about the event and the possible complications that may occur. PMID- 27672459 TI - An Atypical Presentation of Sporadic Jejunal Burkitt's Lymphoma. AB - Burkitt's lymphoma is a very aggressive type of B-cell NHL with replication approaching 100%. Primary gastrointestinal lymphoma is rare. In our case, a 24 year-old male initially presented with symptomatic anemia. He was initially evaluated with colonoscopy and EGD, both of which were unremarkable. A capsule endoscopy was then performed to further evaluate his significant anemia which revealed friable inflamed ulcerated mass in the jejunum. A push enteroscopy was then performed to obtain tissue from the jejunal mass. Biopsy results and immunohistochemical stains were consistent with Burkitt's lymphoma. PET/CT scan revealed only jejunal involvement. Treatment consisted of bowel resection prior to chemotherapy due to concern for perforation with chemotherapy. Patient achieved complete remission after the treatment. PMID- 27672460 TI - Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature. AB - We report a rare case of diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac and a subsequent excisional biopsy of the mass yielded histopathology consistent with DLBCL. Consequently, the patient underwent treatment with R-CHOP therapy. The patient responded well to chemotherapy with a substantial shrinkage in tumor burden and the disease remained localized. Herein, we present a rare case of primary ocular lymphoma, highlight the importance of early diagnosis, and review current treatment modalities. PMID- 27672461 TI - Dementia Improvement after Plasma Exchange for Familial Hypercholesterolemia. AB - Worldwide dementia related memory issues affect a great number of patients and families. In this case, a "senior moment" was noted at age fifty and issues with memory and mind progressed resulting in early retirement from work. The patient described here was given a diagnosis of "Pre-Alzheimer's disease" and presented for further accurate evaluation, diagnosis, and management. The medical management resulted in an improvement in the patients memory and cognitive ability. PMID- 27672462 TI - Reversible Fetal Renal Impairment following Angiotensin Receptor Blocking Treatment during Third Trimester of Pregnancy: Case Report and Review of the Literature. AB - Background. Late pregnancy usage of angiotensin converting enzyme inhibitors (ACE I) and angiotensin II receptor blockers (ARB) may cause severe oligohydramnios due to fetal renal impairment. Affected neonates will often suffer from fatal, renal, and respiratory failure. Case. A 39-year-old multigravida admitted due to anhydramnios secondary to valsartan (ARB) exposure at 30 weeks' gestation. Following secession of treatment amniotic fluid volume returned to normal. Delivery was induced at 34 weeks' gestation following premature rupture of membranes and maternal fever. During the two-year follow-up, no signs of renal insufficiency were noted. Conclusions. This description of reversible fetal renal damage due to ARB intake during pregnancy is the first to show no adverse renal function in a two-year follow-up period. This case may help clinicians counsel patients with pregnancies complicated by exposure to these drugs. PMID- 27672463 TI - A Case of Successful Foraminotomy for Severe Bilateral C5 Palsy following Posterior Decompression and Fusion Surgery for Cervical Ossification of Posterior Longitudinal Ligament. AB - We report a very rare (5~7%) case of bilateral C5 palsy after cervical surgery. A 71-year-old male patient with cervical ossification of posterior longitudinal ligament (OPLL) with foraminal stenosis at bilateral C4/5 underwent posterior decompression and fusion surgery. After surgery, muscle weakness in his both deltoid and biceps was detected and gradually deteriorated to complete paralysis. Postoperative MRI showed sufficient decompression of the spinal cord and posterior shifting. Subsequently, an additional bilateral foraminotomy at C4/5 was performed, with a suspicion that bilateral foraminal stenosis at C4/5 may have been the cause of the paresis. After foraminotomy, muscular contraction was seen in both deltoid and biceps. Finally, complete motor recovery was achieved in a year. Although the gold standard procedure for the prevention and treatment of postoperative C5 palsy has not yet been established, an additional foraminotomy may be recommended for severe C5 palsy in cases of foraminal stenosis even after the occurrence of palsy. PMID- 27672464 TI - Traumatic Testicular Dislocation Associated with Lateral Compression Pelvic Ring Injury and T-Shaped Acetabulum Fracture. AB - We report a case of a unilateral testicular dislocation to the superficial inguinal region associated with a lateral compression type pelvic ring injury (OTA classification 61-C3.3a2, b2, c3) and left T-shaped acetabulum fracture (OTA classification 62-B2) in a 44-year-old male who was in a motorcycle accident. The testicular dislocation was noted during the emergency department primary survey, and its location and viability were verified with ultrasound. The testicle was isolated during surgical stabilization of the left acetabulum through a Pfannenstiel incision and modified-Stoppa approach and returned through the inguinal canal to the scrotum. In follow-up, the patient did not suffer urologic or sexual dysfunction. All motorcycle collision patients presenting with pelvic ring injuries or acetabulum fractures should be worked up for possible testicular dislocation with a scrotal exam. Advanced imaging and a urologic consult may be necessary to detect and treat these injuries. PMID- 27672465 TI - Oral Neurothekeoma of the Right Buccal Mucosa. AB - Oral neurothekeoma or nerve sheath myxoma is a rare benign oral tumour of nerve sheath origin. Historically, this tumour has been subclassified as myxoid (classic), mixed, or the cellular type, depending on the amount of myxoid stroma and cellularity. We present a case of oral neurothekeoma (mixed type) of the buccal mucosa. The tumour was completely excised. No recurrence was detected in the last 3 years after local excision. PMID- 27672466 TI - Leiomyosarcoma Ex Pleomorphic Adenoma of the Parotid Gland: A Case Report and Literature Review. AB - There is only one previously reported incident in the English literature of sarcoma ex pleomorphic adenoma of the parotid and there are only 8 cases of primary parotid leiomyosarcoma. In our case, a 79-year-old female patient presented to our care with left preauricular pain, swelling, and facial weakness. After CT imaging, she underwent left total parotidectomy. A spindle cell lesion was identified intraoperatively and the facial nerve was sacrificed. Subsequent analysis of the lesion yielded a diagnosis of leiomyosarcoma ex pleomorphic adenoma. After 30 fractions of radiation therapy, scans were negative for tumor. However, 18 months after first experiencing symptoms, she was found to have metastases to the brainstem and lung. When diagnosing sarcoma ex pleomorphic adenoma of the parotid gland, it is important to perform thorough immunohistochemical staining and exclude a previous history of sarcoma or other sources of metastases. Complete resection is critical due to the tumor's local aggressiveness and metastatic potential. Although these tumors are not very responsive to chemotherapy or radiation, adjuvant treatment is commonly used when margins are unclear. PMID- 27672468 TI - Lobular Carcinoma of the Breast Metastatic to the Spleen and Accessory Spleen: Report of a Case. AB - Despite the fact that accessory spleen (also known as supernumerary spleen, splenunculus, or splenule) can be found in 10-30% of patients undergoing autopsies, metastatic disease occurring in this organ has been barely reported. A case of lobular breast carcinoma metastatic to the spleen and accessory spleen found incidentally at therapeutic splenectomy for severe anemia and thrombocytopenia is described. On microscopic examination both organs revealed severe fibrocongestive changes and extramedullary hematopoiesis with no obvious carcinomatous involvement. Cytokeratin 7, estrogen receptors, and GATA3 immunohistochemistry disclosed the presence of numerous metastatic breast carcinoma cells infiltrating the splenic parenchyma. This case demonstrates that metastatic carcinoma can be encountered, although rarely, in accessory spleens and that cytokeratin stain should be performed in sections of spleens and/or accessory spleens excised from cancer patients in which the presence of malignant epithelial cells is not recognized on routine sections. PMID- 27672467 TI - Solitary Fibrous Tumor of the Sigmoid Colon Masquerading as an Adnexal Neoplasm. AB - Solitary fibrous tumor is a rare, benign spindle cell neoplasm that was first described in the thoracic pleura. This tumor is now known to occur at many extrapleural sites. There are established criteria for the diagnosis of malignant solitary fibrous tumor including >=4 mitotic figures per 10 high-power fields, increased cellularity, cytologic atypia, infiltrative margins, and/or necrosis. Although all solitary fibrous tumors have the potential to recur or metastasize, those with malignant histologic features tend to behave more aggressively. We report a case of solitary fibrous tumor, with malignant histologic features, in a 21-year-old woman which arose from the serosal surface of the sigmoid colon. PMID- 27672469 TI - Idiopathic Transverse Myelitis Mimicking an Intramedullary Spinal Cord Tumor. AB - The differential diagnoses for spinal cord lesions include spinal tumors and inflammatory processes. The distinction between these pathologies can be difficult if solely based on imaging. We report for the first time to our knowledge a case of idiopathic transverse myelitis (ITM) mimicking a discrete cervical spinal lesion in a 66-year-old man who presented with gait instability and neck pain. The patient's symptoms failed to resolve after an initial course of steroid therapy. Surgical biopsy confirmed the diagnosis of ITM. Subsequent treatment with dexamethasone resulted in complete resolution of the symptoms as well as the intramedullary enhancement. ITM is most common in the cervical and thoracic spine, spanning 3-4 spinal segments. It usually occupies more than 50% of the cross-sectional area of the spinal cord and tends to be central, uniform, and symmetric. It exhibits patchy and peripheral contrast enhancement. These criteria are useful guidelines that help distinguish ITM from neoplastic spinal lesions. A decision to perform biopsy must take into consideration the patient's clinical symptoms, the rate of progression of neurological deficits, and the imaging characteristics of the lesion. Surgical biopsy for questionable lesions should be reserved for patients with progressive neurological deficits refractory to empirical medical therapy. PMID- 27672470 TI - Down-Turner Syndrome: A Case with Double Monoclonal Chromosomal Abnormality. AB - Introduction. The coexistence of Down and Turner syndromes due to double chromosome aneuploidy is very rare; it is even more rare to find the presence of a double monoclonal chromosomal abnormality. Objective. To report a unique case of double monoclonal chromosomal abnormality with trisomy of chromosome 21 and an X ring chromosome in all cells studied; no previous report has been found. Case Report. Female, 28 months old, with pathological short stature from birth, with the following dysmorphic features: tilted upward palpebral fissures, short neck, brachycephaly, and low-set ears. During the neonatal period, the infant presented generalized hypotonia and lymphedema of hands and feet. Karyotype showed 47,X,r(X),+21 [30]. Conclusion. Clinical features of both Down and Turner syndromes were found, highlighting short stature that has remained below 3 z score from birth to the present, associated with delayed psychomotor development. G-banded karyotype analysis in peripheral blood is essential for a definitive diagnosis. PMID- 27672471 TI - Skin Findings in a Patient with Sjogren's Syndrome. AB - Hypergammaglobulinemic purpura (HGP) is a syndrome constellating recurrent purpura, hypergammaglobulinemia, positive rheumatoid factor (RF), anti-Ro/La antibodies, and elevated erythrocyte sedimentation rate (ESR). We present a case of a 29-year-old female who was diagnosed with Sjogren's syndrome four years prior to presenting with rash on her lower extremities for a period of 6 months. Skin biopsy at the initial visit was consistent with leukocytoclastic vasculitis and was initiated on treatment for it. Her rash evolved into 2-5 mm scattered purpurae while she was on the treatment and a repeat biopsy showed extravasation of RBCs, a sparse mononuclear infiltrate with deposition of plasma cells, and no evidence of leukocytoclastic vasculitis, thus showing a transition from neutrophilic to mononuclear inflammatory vascular disease which is a rare occurrence. Hypergammaglobulinemic purpura sometimes turns out to be a challenging disease to manage and requires an integrated effort from the primary care doctors, rheumatologist, and dermatologist. PMID- 27672472 TI - A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy. AB - A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy. PMID- 27672473 TI - An Unusual Case of Abdominal Leiomyoma Presenting as a Free Lying Intraperitoneal Mass in an Elderly Gentleman. AB - Introduction. Leiomyomas are common benign tumours of female reproductive tract and are rarely seen in extrauterine location. Case Report. We report an interesting case of a free lying abdominal leiomyoma presenting as a painless abdominal lump in an elderly gentleman. Discussion. Primary abdominal leiomyomas are uncommon and require surgical removal if symptomatic. PMID- 27672474 TI - Levator Ani Necrosis: An Exceptional Complication Occurring after "High Intensity Focused Ultrasound" of the Prostate. AB - High intensity focused ultrasound (HIFU) is a minimally invasive treatment option that might be considered in the management of localized prostate cancer. It is a well-tolerated treatment with few minor urologic complications and no major toxicities. In this paper, we report to our knowledge the first case of levator ani necrosis in a patient treated with HIFU, manifesting as sturdy perineal pain, which took years of NSAID intake and serial MRIs to demonstrate partial improvement. Therefore, we regard HIFU as a serious potential treatment option that still requires longer follow-up data before its approval in the personalized treatment panel of prostate cancer. PMID- 27672475 TI - Effects of a Comprehensive, Multiple Risky Behavior Prevention Program on High School Students. AB - The purpose of this research study was to examine the effect of a multiple risky behaviors prevention program applied comprehensively throughout an entire school system involving universal, selective, and indicated levels of students at a local private high school during a 4-year period. The noncurriculum prevention program was created based upon the key elements of effective prevention programming and the need to address the growing variety of risky behaviors that the youth face today. Results (n = 469 to 614) indicated that 7 out of 15 risky behaviors statistically significantly decreased throughout the 4-year study, with 6 behaviors involving alcohol and drugs. However, many of the targeted non substance-use risky behaviors displayed inconsistent prevalence rate patterns without statistically significant changes. These findings indicate that the frequency and intensity of programming for non-substance-use behaviors should be increased to a value at least equal to that of the substance-use behaviors. Implications for schools, prevention specialists, and future program development and research are discussed. PMID- 27672476 TI - Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study. AB - Recent mouse studies of the presymptomatic stage of Alzheimer's disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFalpha contributes to increased Abeta production from the Abeta precursor protein (APP), we assessed a putative correlation between APP/Abeta and TNFalpha during the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Abeta was not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFalpha and APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD. PMID- 27672477 TI - Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status. AB - Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD) was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular) and 2 diaphyseal (mainly cortical)). BMD at femoral neck (FN) and lumbar spine L2-4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH), and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of z and T scores and for biochemical measurements. Results. Low BMD z scores were found at metaphyseal regions in the leg (p < 0.001) and in the FN (p < 0.05). The distal metaphyseal region BMD in the leg was lower than spine or FN (p < 0.05). PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD z scores were associated with body weight (p < 0.02), but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight. PMID- 27672478 TI - Polythiophene-Chitosan Magnetic Nanocomposite as a Highly Efficient Medium for Isolation of Fluoxetine from Aqueous and Biological Samples. AB - Polythiophene/chitosan magnetic nanocomposite as an adsorbent of magnetic solid phase extraction was proposed for the isolation of fluoxetine in aqueous and biological samples prior to fluorescence detection at 246 nm. The synthesized nanoparticles, chitosan and polythiophene magnetic nanocomposite, were characterized by scanning electron microscopy, FT-IR, TGA, and EDAX. The separation of the target analyte from the aqueous solution containing the fluoxetine and polythiophene/chitosan magnetic nanocomposite was simply achieved by applying external magnetic field. The main factors affecting the extraction efficiency including desorption conditions, extraction time, ionic strength, and sample solution pH were optimized. The optimum extraction conditions were obtained as 10 min for extraction time, 25 mg for sorbent amount, 50 mL for initial sample volume, methanol as desorption solvent, 1.5 mL for desorption solvent volume, 3 min for desorption time, and being without salt addition. Under the optimum conditions, good linearity was obtained within the range of 15-1000 MUg L(-1) for fluoxetine, with correlation coefficients 0.9994. Furthermore, the method was successfully applied to the determination of fluoxetine in urine and human blood plasma samples. Compared with other methods, the current method is characterized with highly easy, fast separation and low detection limits. PMID- 27672479 TI - Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes. AB - Infection is one of the major causes of failure of orthopedic implants. Our previous study demonstrated that nanotube modification of the implant surface, together with nanotubes loaded with quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), could effectively inhibit bacterial adherence and biofilm formation in vitro. Therefore, the aim of this study was to further investigate the in vitro cytocompatibility with osteogenic cells and the in vivo anti-infection activity of titanium implants with HACC-loaded nanotubes (NT-H). The titanium implant (Ti), nanotubes without polymer loading (NT), and nanotubes loaded with chitosan (NT-C) were fabricated and served as controls. Firstly, we evaluated the cytocompatibility of these specimens with human bone marrow-derived mesenchymal stem cells in vitro. The observation of cell attachment, proliferation, spreading, and viability in vitro showed that NT-H has improved osteogenic activity compared with Ti and NT-C. A prophylaxis rat model with implantation in the femoral medullary cavity and inoculation with methicillin resistant Staphylococcus aureus was established and evaluated by radiographical, microbiological, and histopathological assessments. Our in vivo study demonstrated that NT-H coatings exhibited significant anti-infection capability compared with the Ti and NT-C groups. In conclusion, HACC-loaded nanotubes fabricated on a titanium substrate show good compatibility with osteogenic cells and enhanced anti-infection ability in vivo, providing a good foundation for clinical application to combat orthopedic implant-associated infections. PMID- 27672481 TI - Pregnancy-Related Changes of Amino Acid and Acylcarnitine Concentrations: The Impact of Obesity. AB - Objective Our primary objective was to assess the difference in amino and fatty acid biomarkers throughout pregnancy in women with and without obesity. Interactions between biomarkers and obesity status for associations with maternal and fetal metabolic measures were secondarily analyzed. Methods Overall 39 women (15 cases, 24 controls) were enrolled in this study during their 15- to 20-weeks' visit at the University of Iowa Hospitals and Clinics. We analyzed 32 amino acid and acylcarnitine concentrations with tandem mass spectrometry for differences throughout pregnancy as well as among women with and without obesity (body mass index [BMI] >= 35, BMI < 25). Results There were substantial changes in amino acids and acylcarnitine metabolites between the second and third trimesters (nonfasting state) of pregnancy that were significant after correcting for multiple testing (p < 0.002). Examining differences by maternal obesity, C8:1 (second trimester) and C2, C4-OH, C18:1 (third trimester) were higher in women with obesity compared with women without obesity. Several metabolites were marginally (0.002 < p < 0.05) correlated with birth weight, maternal glucose, and maternal weight gain stratified by obesity status and trimester. Conclusions Understanding maternal metabolism throughout pregnancy and the influence of obesity is a critical step in identifying potential mechanisms that may contribute to adverse outcomes in pregnancies complicated by obesity. PMID- 27672482 TI - Gabapentin Abuse in a Patient with Comorbid Mood and Substance Use Disorders. PMID- 27672483 TI - Criminal Behavior and Borderline Personality: Correlations Among Four Measures. PMID- 27672480 TI - Bone-cartilage crosstalk: a conversation for understanding osteoarthritis. AB - Although cartilage degradation is the characteristic feature of osteoarthritis (OA), it is now recognized that the whole joint is involved in the progression of OA. In particular, the interaction (crosstalk) between cartilage and subchondral bone is thought to be a central feature of this process. The interface between articular cartilage and bone of articulating long bones is a unique zone, which comprises articular cartilage, below which is the calcified cartilage sitting on and intercalated into the subchondral bone plate. Below the subchondral plate is the trabecular bone at the end of the respective long bones. In OA, there are well-described progressive destructive changes in the articular cartilage, which parallel characteristic changes in the underlying bone. This review examines the evidence that biochemical and biomechanical signaling between these tissue compartments is important in OA disease progression and asks whether such signaling might provide possibilities for therapeutic intervention to halt or slow disease development. PMID- 27672484 TI - Pharmaceutical Innovation in the Treatment of Schizophrenia and Mental Disorders Compared with Other Diseases. AB - OBJECTIVES: The objectives of this study were to assess the level of private and public investment in research and development of treatments for schizophrenia and other mental disorders compared to other diseases in order to present data on the economic burden and pharmaceutical innovation by disease area, and to compare the level of investment relative to burden across different diseases. DESIGN: The levels of investment and pharmaceutical innovation relative to burden across different diseases were assessed. Disease burden and prevalence for mental disorders (schizophrenia, bipolar disorder, and major depressive disorder); cancer; rheumatoid arthritis; chronic obstructive pulmonary disorder; diabetes; cardiovascular disease; and neurological disorders (dementia and epilepsy) were estimated from literature sources. SETTING: Pharmaceutical treatment innovation was measured by the total number of drug launches and the number of drugs launched categorized by innovativeness. Research and development expenditures were estimated using published information on annual public and domestic private research and development expenditures by disease area. Lastly, investment relative to disease burden was measured among the set of disease classes for which all three measures were available: schizophrenia, bipolar disorder, major depressive disorder, cancer, rheumatoid arthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and neurology (dementia and epilepsy combined). RESULTS: The level of investment and pharmaceutical innovation in mental disorders was comparatively low, especially relative to the burden of disease. For mental disorders, investment was $3.1 per $1,000 burden invested in research and development for schizophrenia, $1.8 for major depressive disorder, and $0.4 for bipolar disorder relative to cancer ($75.5), chronic obstructive pulmonary disease ($9.4), diabetes ($7.6), cardiovascular disease ($6.3), or rheumatoid arthritis ($5.3). Pharmaceutical innovation was also low for mental disorders. CONCLUSION: Despite the significant burden mental disorders impose on society, investment and pharmaceutical innovation in this disease area remains comparatively low. Policymakers should consider new strategies to stimulate public and private investment in the research and development of novel and effective therapies to treat schizophrenia and other mental disorders. PMID- 27672485 TI - Brexpiprazole: A New Treatment Option for Schizophrenia. AB - Schizophrenia occurs in approximately 0.3 to 0.7 percent of the world's population and is associated with significant morbidity and mortality. Although atypical antipsychotics reduce positive and negative symptoms, they are associated with varying degrees of metabolic adverse effects. This necessitates continued development of efficacious yet metabolically favorable treatments. This article reviews brexpiprazole, a medication recently approved to treat patients with schizophrenia. Brexpiprazole was well-tolerated, and adverse reactions were statistically insignificant. They included nausea; insomnia; headache; agitation; akathisia; and weight gain or changes in lipid, creatine phosphokinase, glucose, or prolactin levels. Brexpiprazole is taken once daily without regard to food, and the dose should be adjusted in patients who receive moderate or strong CYP450 inhibitors or inducers and in patients with hepatic or renal disease. PMID- 27672487 TI - A Case of Treatment- resistant Depression and Body Dysmorphic Disorder: The Role of Electroconvulsive Therapy Revisited. AB - Body dysmorphic disorder is a common, often disabling condition, and is frequently comorbid with major depressive disorder. Selective serotonin reuptake inhibitors constitute first line set of somatic interventions but the management of refractory patients remains challenging. Electroconvulsive therapy, an often highly beneficial treatment for medication resistant-depression, is not considered an effective therapeutic alternative for treatment refractory body dysmorphic disorder. Here we present a 50-year-old woman with body dysmorphic disorder and comorbid major depressive disorder who remained incapacitated and suicidal despite several trials with selective serotonin reuptake inhibitors and antipsychotic medication. Depressive and dysmorphic symptoms appeared to resolve with electroconvulsive therapy, and remission was sustained for two months. Electroconvulsive therapy has an important place in the management of treatment- resistant depression associated with body dysmorphic disorder, and, in select cases, may be effective for dysmorphic symptoms as well. PMID- 27672488 TI - Professional Liability for Forensic Activities: Liability Without a Treatment Relationship. PMID- 27672489 TI - Fahr's Disease or Fahr's Syndrome? PMID- 27672486 TI - The Potential Role of T Helper Cell 22 and IL-22 in Immunopathogenesis of Multiple Sclerosis. AB - Multiple sclerosis is a complex disease with many different immune cells involved in its pathogenesis. Newly identified T helper cell 22 (Th22) is a subset of CD4(+) T cells with specific properties apart from other known CD4(+) T cell subsets with distinguished function and gene expression. Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-alpha (TNF- alpha). The frequency of Th22 and related cytokine IL-22 are increased in various autoimmune diseases. Recently, several studies have reported the changes in frequency and function of Th22 in multiple sclerosis. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of multiple sclerosis disease. PMID- 27672490 TI - A juvenile subfossil crocodylian from Anjohibe Cave, Northwestern Madagascar. AB - Madagascar's subfossil record preserves a diverse community of animals including elephant birds, pygmy hippopotamus, giant lemurs, turtles, crocodiles, bats, rodents, and carnivorans. These fossil accumulations give us a window into the island's past from 80,000 years ago to a mere few hundred years ago, recording the extinction of some groups and the persistence of others. The crocodylian subfossil record is limited to two taxa, Voay robustus and Crocodylus niloticus, found at sites distributed throughout the island. V. robustus is extinct while C. niloticus is still found on the island today, but whether these two species overlapped temporally, or if Voay was driven to extinction by competing with Crocodylus remains unknown. While their size and presumed behavior was similar to each other, nearly nothing is known about the growth and development of Voay, as the overwhelming majority of fossil specimens represent mature adult individuals. Here we describe a nearly complete juvenile crocodylian specimen from Anjohibe Cave, northwestern Madagascar. The specimen is referred to Crocodylus based on the presence of caviconchal recesses on the medial wall of the maxillae, and to C. niloticus based on the presence of an oval shaped internal choana, lack of rostral ornamentation and a long narrow snout. However, as there are currently no described juvenile specimens of Voay robustus, it is important to recognize that some of the defining characteristics of that genus may have changed through ontogeny. Elements include a nearly complete skull and many postcranial elements (cervical, thoracic, sacral, and caudal vertebrae, pectoral elements, pelvic elements, forelimb and hindlimb elements, osteoderms). Crocodylus niloticus currently inhabits Madagascar but is locally extinct from this particular region; radiometric dating indicates an age of ~460-310 years before present (BP). This specimen clearly represents a juvenile based on the extremely small size and open sutures/detached neural arches; total body length is estimated to be ~1.1 m (modern adults of this species range from ~4-6 m). This fossil represents the only juvenile subfossil crocodylian specimen reported from Madagascar. PMID- 27672491 TI - Talk the talk and walk the walk. Evaluation of autonomy in aging and Alzheimer disease by simulating instrumental activities of daily living: the S-IADL. AB - OBJECTIVE: The autonomy of individuals is linked to the achievement of instrumental activities of daily living that require complex behavior. In the elderly, the assessment of autonomy is usually based on questionnaires that have strong subjective constraints. Considering this fact, we tested elderly healthy adults and Alzheimer disease patients using a new measure, the S-IADL (Simulation of Instrumental Activities for Daily Living), to assess the ability to perform effectively activities of daily living. METHOD: The S-IADL shares many items with the well-known IADL questionnaire proposed by Lawton & Brody (1969). However, as opposed to the IADL, the assessment of autonomy is not based on the completion of a questionnaire but requires the realization or simulation of various activities of daily living. Eighty-three participants (69 healthy elderly, and 14 Alzheimer Disease patients) completed the IADL and performed the S-IADL assessment. RESULTS: Results revealed that, like the IADL, the S-IADL is able to identify AD patients who are likely to encounter difficulties in performing everyday activities, and no major differences were found between the IADL and the S-IADL. CONCLUSIONS: We outlined some advantages for prefering, in certain situation, this new tool based on simulation of activities in functional evaluation. Finally, we discuss the main limits of the S-IADL that should be investigated prior to its utilization by clinicians. PMID- 27672492 TI - Emotion recognition using Kinect motion capture data of human gaits. AB - Automatic emotion recognition is of great value in many applications, however, to fully display the application value of emotion recognition, more portable, non intrusive, inexpensive technologies need to be developed. Human gaits could reflect the walker's emotional state, and could be an information source for emotion recognition. This paper proposed a novel method to recognize emotional state through human gaits by using Microsoft Kinect, a low-cost, portable, camera based sensor. Fifty-nine participants' gaits under neutral state, induced anger and induced happiness were recorded by two Kinect cameras, and the original data were processed through joint selection, coordinate system transformation, sliding window gauss filtering, differential operation, and data segmentation. Features of gait patterns were extracted from 3-dimentional coordinates of 14 main body joints by Fourier transformation and Principal Component Analysis (PCA). The classifiers NaiveBayes, RandomForests, LibSVM and SMO (Sequential Minimal Optimization) were trained and evaluated, and the accuracy of recognizing anger and happiness from neutral state achieved 80.5% and 75.4%. Although the results of distinguishing angry and happiness states were not ideal in current study, it showed the feasibility of automatically recognizing emotional states from gaits, with the characteristics meeting the application requirements. PMID- 27672493 TI - Microbial diversity of extreme habitats in human homes. AB - High-throughput sequencing techniques have opened up the world of microbial diversity to scientists, and a flurry of studies in the most remote and extreme habitats on earth have begun to elucidate the key roles of microbes in ecosystems with extreme conditions. These same environmental extremes can also be found closer to humans, even in our homes. Here, we used high-throughput sequencing techniques to assess bacterial and archaeal diversity in the extreme environments inside human homes (e.g., dishwashers, hot water heaters, washing machine bleach reservoirs, etc.). We focused on habitats in the home with extreme temperature, pH, and chemical environmental conditions. We found a lower diversity of microbes in these extreme home environments compared to less extreme habitats in the home. However, we were nonetheless able to detect sequences from a relatively diverse array of bacteria and archaea. Habitats with extreme temperatures alone appeared to be able to support a greater diversity of microbes than habitats with extreme pH or extreme chemical environments alone. Microbial diversity was lowest when habitats had both extreme temperature and one of these other extremes. In habitats with both extreme temperatures and extreme pH, taxa with known associations with extreme conditions dominated. Our findings highlight the importance of examining interactive effects of multiple environmental extremes on microbial communities. Inasmuch as taxa from extreme environments can be both beneficial and harmful to humans, our findings also suggest future work to understand both the threats and opportunities posed by the life in these habitats. PMID- 27672494 TI - Functional, size and taxonomic diversity of fish along a depth gradient in the deep sea. AB - Biodiversity is well studied in ecology and the concept has been developed to include traits of species, rather than solely taxonomy, to better reflect the functional diversity of a system. The deep sea provides a natural environmental gradient within which to study changes in different diversity metrics, but traits of deep-sea fish are not widely known, hampering the application of functional diversity to this globally important system. We used morphological traits to determine the functional richness and functional divergence of demersal fish assemblages along the continental slope in the Northeast Atlantic, at depths of 300-2,000 m. We compared these metrics to size diversity based on individual body size and species richness. Functional richness and size diversity showed similar patterns, with the highest diversity at intermediate depths; functional divergence showed the opposite pattern, with the highest values at the shallowest and deepest parts of the study site. Species richness increased with depth. The functional implications of these patterns were deduced by examining depth-related changes in morphological traits and the dominance of feeding guilds as illustrated by stable isotope analyses. The patterns in diversity and the variation in certain morphological traits can potentially be explained by changes in the relative dominance of pelagic and benthic feeding guilds. All measures of diversity examined here suggest that the deep areas of the continental slope may be equally or more diverse than assemblages just beyond the continental shelf. PMID- 27672495 TI - Decoupling social status and status certainty effects on health in macaques: a network approach. AB - BACKGROUND: Although a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and relational components (perceived social status, dominance interactions). In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models) and dominance certainty (the relative certainty vs. ambiguity of an individual's status), allowing for a more complex examination of how social status impacts health. METHODS: Behavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects). Subjects' general physical health (diarrhea) was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP)). RESULTS: Dominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea. DISCUSSION: Social status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one's social status in status-health research. This work also suggests that in order to fully explore the mechanisms for how social life influences health, more complex metrics of social systems and their dynamics are needed. PMID- 27672496 TI - Mischievous responding in Internet Gaming Disorder research. AB - The most recent update to the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included Internet Gaming Disorder as a new potential psychiatric condition that merited further scientific study. The present research was conducted in response to the APA Substance Related Disorders Working Group's research call to estimate the extent to which mischievous responding-a known problematic pattern of participant self-report responding in questionnaires-is relevant to Internet Gaming Disorder research. In line with a registered sampling and analysis plan, findings from two studies (n tot = 11,908) provide clear evidence that mischievous responding is positively associated with the number of Internet Gaming Disorder indicators participants report. Results are discussed in the context of ongoing problem gaming research and the discussion provides recommendations for improving the quality of scientific practice in this area. PMID- 27672497 TI - Distinctive personality profiles of fibromyalgia and chronic fatigue syndrome patients. AB - OBJECTIVE: The current study is an innovative exploratory investigation, aiming at identifying differences in personality profiles within Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome (CFS) patients. METHOD: In total, 344 participants (309 female, 35 male) reported suffering from FMS and/or CFS and consented to participate in the study. Participants were recruited at an Israeli FM/CFS patient meeting held in May 2013, and through an announcement posted on several social networks. Participants were asked to complete a research questionnaire, which included FMS criteria and severity scales, and measures of personality, emotional functioning, positivity, social support and subjective assessment of general health. In total, 204 participants completed the research questionnaire (40.7% attrition rate). RESULTS: A cluster analysis produced two distinct clusters, which differed significantly on psychological variables, but did not differ on demographic variables or illness severity. As compared to cluster number 2 (N = 107), participants classified into cluster number 1 (N = 97) showed a less adaptive pattern, with higher levels of Harm Avoidance and Alexithymia; higher prevalence of Type D personality; and lower levels of Persistence (PS), Reward dependence (RD), Cooperation, Self-directedness (SD), social support and positivity. CONCLUSION: The significant pattern of results indicates at least two distinct personality profiles of FM and CFS patients. Findings from this research may help improve the evaluation and treatment of FM and CFS patients, based on each patient's unique needs, psychological resources and weaknesses, as proposed by the current trend of personalized medicine. PMID- 27672498 TI - Effect of fragmentation on the Costa Rican dry forest avifauna. AB - Deforestation and changes in land use have reduced the tropical dry forest to isolated forest patches in northwestern Costa Rica. We examined the effect of patch area and length of the dry season on nestedness of the entire avian community, forest fragment assemblages, and species occupancy across fragments for the entire native avifauna, and for a subset of forest dependent species. Species richness was independent of both fragment area and distance between fragments. Similarity in bird community composition between patches was related to habitat structure; fragments with similar forest structure have more similar avian assemblages. Size of forest patches influenced nestedness of the bird community and species occupancy, but not nestedness of assemblages across patches in northwestern Costa Rican avifauna. Forest dependent species (species that require large tracts of mature forest) and assemblages of these species were nested within patches ordered by a gradient of seasonality, and only occupancy of species was nested by area of patches. Thus, forest patches with a shorter dry season include more forest dependent species. PMID- 27672501 TI - Comparative cephalopod shell strength and the role of septum morphology on stress distribution. AB - The evolution of complexly folded septa in ammonoids has long been a controversial topic. Explanations of the function of these folded septa can be divided into physiological and mechanical hypotheses with the mechanical functions tending to find widespread support. The complexity of the cephalopod shell has made it difficult to directly test the mechanical properties of these structures without oversimplification of the septal morphology or extraction of a small sub-domain. However, the power of modern finite element analysis now permits direct testing of mechanical hypothesis on complete, empirical models of the shells taken from computed tomographic data. Here we compare, for the first time using empirical models, the capability of the shells of extant Nautilus pompilius, Spirula spirula, and the extinct ammonite Cadoceras sp. to withstand hydrostatic pressure and point loads. Results show hydrostatic pressure imparts highest stress on the final septum with the rest of the shell showing minimal compression. S. spirula shows the lowest stress under hydrostatic pressure while N. pompilius shows the highest stress. Cadoceras sp. shows the development of high stress along the attachment of the septal saddles with the shell wall. Stress due to point loads decreases when the point force is directed along the suture as opposed to the unsupported chamber wall. Cadoceras sp. shows the greatest decrease in stress between the point loads compared to all other models. Greater amplitude of septal flutes corresponds with greater stress due to hydrostatic pressure; however, greater amplitude decreases the stress magnitude of point loads directed along the suture. In our models, sutural complexity does not predict greater resistance to hydrostatic pressure but it does seem to increase resistance to point loads, such as would be from predators. This result permits discussion of palaeoecological reconstructions on the basis of septal morphology. We further suggest that the ratio used to characterize septal morphology in the septal strength index and in calculations of tensile strength of nacre are likely insufficient. A better understanding of the material properties of cephalopod nacre may allow the estimation of maximum depth limits of shelled cephalopods through finite element analysis. PMID- 27672499 TI - Characterization of novel bacteriophage phiC119 capable of lysing multidrug resistant Shiga toxin-producing Escherichia coli O157:H7. AB - BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) is one of the most common and widely distributed foodborne pathogens that has been frequently implicated in gastrointestinal and urinary tract infections. Moreover, high rates of multiple antibiotic-resistant E. coli strains have been reported worldwide. Due to the emergence of antibiotic-resistant strains, bacteriophages are considered an attractive alternative to biocontrol pathogenic bacteria. Characterization is a preliminary step towards designing a phage for biocontrol. METHODS: In this study, we describe the characterization of a bacteriophage designated phiC119, which can infect and lyse several multidrug-resistant STEC strains and some Salmonella strains. The phage genome was screened to detect the stx-genes using PCR, morphological analysis, host range was determined, and genome sequencing were carried out, as well as an analysis of the cohesive ends and identification of the type of genetic material through enzymatic digestion of the genome. RESULTS: Analysis of the bacteriophage particles by transmission electron microscopy showed that it had an icosahedral head and a long tail, characteristic of the family Siphoviridae. The phage exhibits broad host range against multidrug-resistant and highly virulent E. coli isolates. One-step growth experiments revealed that the phiC119 phage presented a large burst size (210 PFU/cell) and a latent period of 20 min. Based on genomic analysis, the phage contains a linear double-stranded DNA genome with a size of 47,319 bp. The phage encodes 75 putative proteins, but lysogeny and virulence genes were not found in the phiC119 genome. CONCLUSION: These results suggest that phage phiC119 may be a good biological control agent. However, further studies are required to ensure its control of STEC and to confirm the safety of phage use. PMID- 27672500 TI - Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls. AB - BACKGROUND: The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. METHODS: Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data dependent acquisition mode. RESULTS: We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. CONCLUSIONS: Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease associated characteristics of metabolic activity. PMID- 27672502 TI - The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets. AB - An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%-99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development. PMID- 27672504 TI - Muscle size explains low passive skeletal muscle force in heart failure patients. AB - BACKGROUND: Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. METHODS: Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. RESULTS: We found reduced passive SOL forces (~30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. DISCUSSION: These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening. PMID- 27672503 TI - Genetic signatures of ecological diversity along an urbanization gradient. AB - Despite decades of work in environmental science and ecology, estimating human influences on ecosystems remains challenging. This is partly due to complex chains of causation among ecosystem elements, exacerbated by the difficulty of collecting biological data at sufficient spatial, temporal, and taxonomic scales. Here, we demonstrate the utility of environmental DNA (eDNA) for quantifying associations between human land use and changes in an adjacent ecosystem. We analyze metazoan eDNA sequences from water sampled in nearshore marine eelgrass communities and assess the relationship between these ecological communities and the degree of urbanization in the surrounding watershed. Counter to conventional wisdom, we find strongly increasing richness and decreasing beta diversity with greater urbanization, and similar trends in the diversity of life histories with urbanization. We also find evidence that urbanization influences nearshore communities at local (hundreds of meters) rather than regional (tens of km) scales. Given that different survey methods sample different components of an ecosystem, we then discuss the advantages of eDNA-which we use here to detect hundreds of taxa simultaneously-as a complement to traditional ecological sampling, particularly in the context of broad ecological assessments where exhaustive manual sampling is impractical. Genetic data are a powerful means of uncovering human-ecosystem interactions that might otherwise remain hidden; nevertheless, no sampling method reveals the whole of a biological community. PMID- 27672505 TI - Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins. AB - BACKGROUND: Papillary thyroid cancer (PTC) is mainly diagnosed using fine-needle aspiration biopsy. This most common form of well-differentiated thyroid cancer occurs with or without a background of benign thyroid goiter (BTG). METHODS: In the present study, a gel-based proteomics analysis was performed to analyse the expression of proteins in tissue and serum samples of PTC patients with (PTCb; n = 6) and without a history of BTG (PTCa; n = 8) relative to patients with BTG (n = 20). This was followed by confirmation of the levels of proteins which showed significant altered abundances of more than two-fold difference (p < 0.01) in the tissue and serum samples of the same subjects using ELISA. RESULTS: The data of our study showed that PTCa and PTCb distinguish themselves from BTG in the types of tissue and serum proteins of altered abundance. While higher levels of alpha-1 antitrypsin (A1AT) and heat shock 70 kDa protein were associated with PTCa, lower levels of A1AT, protein disulfide isomerase and ubiquitin-conjugating enzyme E2 N seemed apparent in the PTCb. In case of the serum proteins, higher abundances of A1AT and alpha 1-beta glycoprotein were detected in PTCa, while PTCb was associated with enhanced apolipoprotein A-IV and alpha 2-HS glycoprotein (AHSG). The different altered expression of tissue and serum A1AT as well as serum AHSG between PTCa and PTCb patients were also validated by ELISA. DISCUSSION: The distinctive altered abundances of the tissue and serum proteins form preliminary indications that PTCa and PTCb are two distinct cancers of the thyroid that are etiologically and mechanistically different although it is currently not possible to rule out that they may also be due other reasons such as the different stages of the malignant disease. These proteins stand to have a potential use as tissue or serum biomarkers to discriminate the three different thyroid neoplasms although this requires further validation in clinically representative populations. PMID- 27672506 TI - Gua Sha, a press-stroke treatment of the skin, boosts the immune response to intradermal vaccination. AB - OBJECTIVE: The skin is an important immunological barrier of the body as well as an optimal route for vaccine administration. Gua Sha, which involves press-stroke treatment of the skin, is an effective folk therapy, widely accepted in East Asia, for various symptoms; however, the mechanisms underlying its therapeutic effects have not been clarified. We investigated the influence of Gua Sha on the immunological features of the skin. METHODS: Gua Sha was performed on BALB/c mice and the effects were evaluated using anatomical, histological, and cytometric methods as well as cytokine determination locally and systemically. The effect on intradermal vaccination was assessed with antigen-specific subtype antibody responses. RESULTS: Blood vessel expansion, erythrocyte extravasation, and increased ratios of immune active cells were observed in the skin tissue following the treatment. Pro-inflammatory cytokines were up-regulated, and immunosuppressive cytokines, down-regulated, in the treated and untreated skin and systemic circulation; no obvious variations were detected in case of anti inflammatory cytokines. Interestingly, intradermal delivery of a model vaccine following Gua Sha induced about three-fold higher IgG titers with a more Th1 biased antibody subtype profile. CONCLUSION: Gua Sha treatment can up-regulate the innate and adaptive immune functions of the skin and boost the response against intradermal antigens. Thus, Gua Sha may serve as a safe, inexpensive, and independent physical adjuvant for intradermal vaccination. PMID- 27672507 TI - Canopy position has a profound effect on soybean seed composition. AB - Although soybean seeds appear homogeneous, their composition (protein, oil and mineral concentrations) can vary significantly with the canopy position where they were produced. In studies with 10 cultivars grown over a 3-yr period, we found that seeds produced at the top of the canopy have higher concentrations of protein but less oil and lower concentrations of minerals such as Mg, Fe, and Cu compared to seeds produced at the bottom of the canopy. Among cultivars, mean protein concentration (average of different positions) correlated positively with mean concentrations of S, Zn and Fe, but not other minerals. Therefore, on a whole plant basis, the uptake and allocation of S, Zn and Fe to seeds correlated with the production and allocation of reduced N to seed protein; however, the reduced N and correlated minerals (S, Zn and Fe) showed different patterns of allocation among node positions. For example, while mean concentrations of protein and Fe correlated positively, the two parameters correlated negatively in terms of variation with canopy position. Altering the microenvironment within the soybean canopy by removing neighboring plants at flowering increased protein concentration in particular at lower node positions and thus altered the node position gradient in protein (and oil) without altering the distribution of Mg, Fe and Cu, suggesting different underlying control mechanisms. Metabolomic analysis of developing seeds at different positions in the canopy suggests that availability of free asparagine may be a positive determinant of storage protein accumulation in seeds and may explain the increased protein accumulation in seeds produced at the top of the canopy. Our results establish node-position variation in seed constituents and provide a new experimental system to identify genes controlling key aspects of seed composition. In addition, our results provide an unexpected and simple approach to link agronomic practices to improve human nutrition and health in developing countries because food products produced from seeds at the bottom of the canopy contained higher Fe concentrations than products from the top of the canopy. Therefore, using seeds produced in the lower canopy for production of iron-rich soy foods for human consumption could be important when plants are the major source of protein and human diets can be chronically deficient in Fe and other minerals. PMID- 27672508 TI - Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro. AB - Progesterone (P4), an ovarian steroid hormone, is an important regulator of female reproduction. In this study, we explored the influence of progesterone on porcine oocyte nuclear maturation and cytoplasmic maturation and development in vitro. We found that the presence of P4 during oocyte maturation did not inhibit polar body extrusions but significantly increased glutathione and decreased reactive oxygen species (ROS) levels relative to that in control groups. The incidence of parthenogenetically activated oocytes that could develop to the blastocyst stage was higher (p < 0.05) when oocytes were exposed to P4 as compared to that in the controls. Cell numbers were increased in the P4-treated groups. Further, the P4-specific inhibitor mifepristone (RU486) prevented porcine oocyte maturation, as represented by the reduced incidence (p < 0.05) of oocyte first polar body extrusions. RU486 affected maturation promoting factor (MPF) activity and maternal mRNA polyadenylation status. In general, these data show that P4 influences the cytoplasmic maturation of porcine oocytes, at least partially, by decreasing their polyadenylation, thereby altering maternal gene expression. PMID- 27672509 TI - Lowland tapir distribution and habitat loss in South America. AB - The development of species distribution models (SDMs) can help conservation efforts by generating potential distributions and identifying areas of high environmental suitability for protection. Our study presents a distribution and habitat map for lowland tapir in South America. We also describe the potential habitat suitability of various geographical regions and habitat loss, inside and outside of protected areas network. Two different SDM approaches, MAXENT and ENFA, produced relative different Habitat Suitability Maps for the lowland tapir. While MAXENT was efficient at identifying areas as suitable or unsuitable, it was less efficient (when compared to the results by ENFA) at identifying the gradient of habitat suitability. MAXENT is a more multifaceted technique that establishes more complex relationships between dependent and independent variables. Our results demonstrate that for at least one species, the lowland tapir, the use of a simple consensual approach (average of ENFA and MAXENT models outputs) better reflected its current distribution patterns. The Brazilian ecoregions have the highest habitat loss for the tapir. Cerrado and Atlantic Forest account for nearly half (48.19%) of the total area lost. The Amazon region contains the largest area under protection, and the most extensive remaining habitat for the tapir, but also showed high levels of habitat loss outside protected areas, which increases the importance of support for proper management. PMID- 27672510 TI - Regional drivers of clutch loss reveal important trade-offs for beach-nesting birds. AB - Coastal birds are critical ecosystem constituents on sandy shores, yet are threatened by depressed reproductive success resulting from direct and indirect anthropogenic and natural pressures. Few studies examine clutch fate across the wide range of environments experienced by birds; instead, most focus at the small site scale. We examine survival of model shorebird clutches as an index of true clutch survival at a regional scale (~200 km), encompassing a variety of geomorphologies, predator communities, and human use regimes in southeast Queensland, Australia. Of the 132 model nests deployed and monitored with cameras, 45 (34%) survived the experimental exposure period. Thirty-five (27%) were lost to flooding, 32 (24%) were depredated, nine (7%) buried by sand, seven (5%) destroyed by people, three (2%) failed by unknown causes, and one (1%) was destroyed by a dog. Clutch fate differed substantially among regions, particularly with respect to losses from flooding and predation. 'Topographic' exposure was the main driver of mortality of nests placed close to the drift line near the base of dunes, which were lost to waves (particularly during storms) and to a lesser extent depredation. Predators determined the fate of clutches not lost to waves, with the depredation probability largely influenced by region. Depredation probability declined as nests were backed by higher dunes and were placed closer to vegetation. This study emphasizes the scale at which clutch fate and survival varies within a regional context, the prominence of corvids as egg predators, the significant role of flooding as a source of nest loss, and the multiple trade-offs faced by beach-nesting birds and those that manage them. PMID- 27672512 TI - An association between feather damaging behavior and corticosterone metabolite excretion in captive African grey parrots (Psittacus erithacus). AB - BACKGROUND: African grey parrots (Psittacus erithacus) are kept as pets and are frequently hand-reared. It has been observed that hand-reared African grey parrots may develop behavioral disorders such as feather damaging behavior (FDB). It is well known that chronic stress is involved in behavioral disorders in captive parrots. The main glucocorticoid in birds is corticosterone; its quantification provides information about adrenocortical activity and is considered to be a reliable indicator of stress levels in birds. We analyzed the differences in the excretion of corticosterone metabolites (CM) in the droppings of African grey parrots characterized by: 1. different rearing histories (parent rearing vs. hand rearing); and 2. the presence or absence of FDB in hand-reared parrots. METHODS: A total of 82 African grey parrots that were kept in captivity were considered. According to breeding methods, three groups of birds were defined: 1. The parent-reared (PR) parrots included birds kept in pairs (n = 30 pairs) with a conspecific partner of the opposite sex. All of these birds were healthy and never showed FDB signs; 2. The healthy hand-reared parrots (H-HR) included pet parrots individually kept, that were hand-reared and did not display any sign of FDB (n = 11, 7 males and 4 females); 3. The FDB hand-reared parrot (FDB-HR) included pet parrots individually kept, that were hand-reared and displayed FDB (n = 11, 7 males and 4 females). Droppings were collected in the morning over three alternating days in autumn 2014 and spring 2015. The CM were determined using a multi-species corticosterone enzyme immunoassay kit. Split plot repeated-measure ANOVA was used to examine any differences using group, season and group * season as the main factors. RESULTS: Different quantities of CM in droppings were found for the three groups. The mean CM value was 587 ng/g in the PR parrots, 494 ng/g in the H-HR parrots and 1,744 ng/g in the FDB-HR parrots, irrespective of the season. The excretion of CM in FDB-HR was significantly higher than in PR or H-HR parrots. CM in droppings were not influenced by the season (autumn vs. spring); furthermore, the interaction between group and sampling season was not significant. Limited to the H-HR and FDB-HR groups, a trend in the significance of the difference in the mean CM excreted by male and female birds was observed, with the levels excreted by males being higher than those excreted by females. When the effect of age was considered (in the two separate groups), there was a statistically significant positive correlation only for H-HR. CONCLUSIONS: The highest amount of CM excretion was found in FDB-HR parrots, and a positive correlation between age and CM excretion was found in H-HR. Given that the CM excretion of both PR and H-HR parrots was similar in our study, future research is recommended to investigate the specific aspects of hand-rearing to improve parrot welfare. PMID- 27672511 TI - Bcl-2 homologue Debcl enhances alpha-synuclein-induced phenotypes in Drosophila. AB - BACKGROUND: Parkinson disease (PD) is a debilitating movement disorder that afflicts 1-2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized Debcl and the antiapoptotic Buffy. The expression of the human transgene alpha-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA) of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression of Debcl in the DA neurons and neuron-rich eye and along with the expression of alpha-synuclein offers an opportunity to highlight the role of Debcl in mitochondrial-dependent neuronal degeneration and death. RESULTS: The directed overexpression of Debcl using the Ddc-Gal4 transgene in the DA of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of Debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of Debcl in the alpha-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of Debcl along with Buffy partially counteracts the Debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of Debcl along with the expression of alpha synuclein in the eye, enhanced the eye ablation that results from the overexpression of Debcl. The co-expression of Buffy along with Debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of Debcl partially restores the eye to a roughened eye phenotype. DISCUSSION: The overexpression of Debcl in DA neurons produces flies with shortened lifespan and impaired locomotor ability, phenotypes that are strongly associated with models of PD in Drosophila. The co expression of Debcl along with alpha-synuclein enhanced the PD-like phenotypes. The co-expression of Debcl along with Buffy suppresses these phenotypes. Complementary experiments in the Drosophila eye show similar trends during development. Taken all together these results suggest a role for Debcl in neurodegenerative disorders. PMID- 27672513 TI - Resilience does not explain the dissociation between chronic pain and physical activity in South Africans living with HIV. AB - Pain burden is high in people living with HIV (PLWH), but the effect of this pain on functionality is equivocal. Resilience, the ability to cope with adversity, may promote adaptation to pain, so we hypothesised that higher resilience would correlate with less pain-related impairment of activity. We recruited 197 black South African PLWH, 99 with chronic pain (CP) and 98 patients without. We measured pain intensity and interference using the Brief Pain Inventory, and resilience using the Resilience Scale. Participants were generally highly resilient. Greater resilience correlated with better health-related quality of life, but not with pain intensity or interference. We also measured physical activity objectively, by actigraphy, in a subset of patients (37 with chronic pain and 31 without chronic pain), who wore accelerometers for two weeks. There was no difference in duration or intensity of activity between those with and without pain, and activity was not associated with resilience. In this sample, pain was not associated with altered physical activity. Resilience did not explain differences in pain intensity or pain interference but was associated with improved quality of life. Financial stresses and the fear of HIV stigma may have driven patients to conceal pain and to suppress its expected impairment of activity. PMID- 27672514 TI - Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets. AB - Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures. PMID- 27672515 TI - A 'post-honeymoon' measles epidemic in Burundi: mathematical model-based analysis and implications for vaccination timing. AB - Using a mathematical model with realistic demography, we analyze a large outbreak of measles in Muyinga sector in rural Burundi in 1988-1989. We generate simulated epidemic curves and age * time epidemic surfaces, which we qualitatively and quantitatively compare with the data. Our findings suggest that supplementary immunization activities (SIAs) should be used in places where routine vaccination cannot keep up with the increasing numbers of susceptible individuals resulting from population growth or from logistical problems such as cold chain maintenance. We use the model to characterize the relationship between SIA frequency and SIA age range necessary to suppress measles outbreaks. If SIAs are less frequent, they must expand their target age range. PMID- 27672517 TI - A workflow to preserve genome-quality tissue samples from plants in botanical gardens and arboreta. AB - PREMISE OF THE STUDY: Internationally, gardens hold diverse living collections that can be preserved for genomic research. Workflows have been developed for genomic tissue sampling in other taxa (e.g., vertebrates), but are inadequate for plants. We outline a workflow for tissue sampling intended for two audiences: botanists interested in genomics research and garden staff who plan to voucher living collections. METHODS AND RESULTS: Standard herbarium methods are used to collect vouchers, label information and images are entered into a publicly accessible database, and leaf tissue is preserved in silica and liquid nitrogen. A five-step approach for genomic tissue sampling is presented for sampling from living collections according to current best practices. CONCLUSIONS: Collecting genome-quality samples from gardens is an economical and rapid way to make available for scientific research tissue from the diversity of plants on Earth. The Global Genome Initiative will facilitate and lead this endeavor through international partnerships. PMID- 27672516 TI - Whole genome sequencing of Streptococcus pneumoniae: development, evaluation and verification of targets for serogroup and serotype prediction using an automated pipeline. AB - Streptococcus pneumoniae typically express one of 92 serologically distinct capsule polysaccharide (cps) types (serotypes). Some of these serotypes are closely related to each other; using the commercially available typing antisera, these are assigned to common serogroups containing types that show cross reactivity. In this serotyping scheme, factor antisera are used to allocate serotypes within a serogroup, based on patterns of reactions. This serotyping method is technically demanding, requires considerable experience and the reading of the results can be subjective. This study describes the analysis of the S. pneumoniae capsular operon genetic sequence to determine serotype distinguishing features and the development, evaluation and verification of an automated whole genome sequence (WGS)-based serotyping bioinformatics tool, PneumoCaT (Pneumococcal Capsule Typing). Initially, WGS data from 871 S. pneumoniae isolates were mapped to reference cps locus sequences for the 92 serotypes. Thirty-two of 92 serotypes could be unambiguously identified based on sequence similarities within the cps operon. The remaining 60 were allocated to one of 20 'genogroups' that broadly correspond to the immunologically defined serogroups. By comparing the cps reference sequences for each genogroup, unique molecular differences were determined for serotypes within 18 of the 20 genogroups and verified using the set of 871 isolates. This information was used to design a decision-tree style algorithm within the PneumoCaT bioinformatics tool to predict to serotype level for 89/94 (92 + 2 molecular types/subtypes) from WGS data and to serogroup level for serogroups 24 and 32, which currently comprise 2.1% of UK referred, invasive isolates submitted to the National Reference Laboratory (NRL), Public Health England (June 2014-July 2015). PneumoCaT was evaluated with an internal validation set of 2065 UK isolates covering 72/92 serotypes, including 19 non-typeable isolates and an external validation set of 2964 isolates from Thailand (n = 2,531), USA (n = 181) and Iceland (n = 252). PneumoCaT was able to predict serotype in 99.1% of the typeable UK isolates and in 99.0% of the non-UK isolates. Concordance was evaluated in UK isolates where further investigation was possible; in 91.5% of the cases the predicted capsular type was concordant with the serologically derived serotype. Following retesting, concordance increased to 99.3% and in most resolved cases (97.8%; 135/138) discordance was shown to be caused by errors in original serotyping. Replicate testing demonstrated that PneumoCaT gave 100% reproducibility of the predicted serotype result. In summary, we have developed a WGS-based serotyping method that can predict capsular type to serotype level for 89/94 serotypes and to serogroup level for the remaining four. This approach could be integrated into routine typing workflows in reference laboratories, reducing the need for phenotypic immunological testing. PMID- 27672518 TI - Small unmanned aerial vehicles (micro-UAVs, drones) in plant ecology. AB - PREMISE OF THE STUDY: Low-elevation surveys with small aerial drones (micro unmanned aerial vehicles [UAVs]) may be used for a wide variety of applications in plant ecology, including mapping vegetation over small- to medium-sized regions. We provide an overview of methods and procedures for conducting surveys and illustrate some of these applications. METHODS: Aerial images were obtained by flying a small drone along transects over the area of interest. Images were used to create a composite image (orthomosaic) and a digital surface model (DSM). Vegetation classification was conducted manually and using an automated routine. Coverage of an individual species was estimated from aerial images. RESULTS: We created a vegetation map for the entire region from the orthomosaic and DSM, and mapped the density of one species. Comparison of our manual and automated habitat classification confirmed that our mapping methods were accurate. A species with high contrast to the background matrix allowed adequate estimate of its coverage. DISCUSSION: The example surveys demonstrate that small aerial drones are capable of gathering large amounts of information on the distribution of vegetation and individual species with minimal impact to sensitive habitats. Low-elevation aerial surveys have potential for a wide range of applications in plant ecology. PMID- 27672519 TI - Development and characterization of 27 microsatellite markers for the mangrove fern, Acrostichum aureum (Pteridaceae). AB - PREMISE OF THE STUDY: Twenty-seven nuclear microsatellite markers were developed for the mangrove fern, Acrostichum aureum (Pteridaceae), to investigate the genetic structure and demographic history of the only pantropical mangrove plant. METHODS AND RESULTS: Fifty-six A. aureum individuals from three populations were sampled and genotyped to characterize the 27 loci. The number of alleles and expected heterozygosity ranged from one to 15 and 0.000 to 0.893, respectively. Across the 26 polymorphic loci, the Malaysian population showed much higher levels of polymorphism compared to the other two populations in Guam and Brazil. Cross-amplification tests in the other two species from the genus determined that seven and six loci were amplifiable in A. danaeifolium and A. speciosum, respectively. CONCLUSIONS: The 26 polymorphic microsatellite markers will be useful for future studies investigating the genetic structure and demographic history of of A. aureum, which has the widest distributional range of all mangrove plants. PMID- 27672520 TI - Characterization of microsatellite loci in the lichen-forming fungus Cetraria aculeata (Parmeliaceae, Ascomycota). AB - PREMISE OF THE STUDY: Polymorphic microsatellite markers were developed for the lichen species Cetraria aculeata (Parmeliaceae) to study fine-scale population diversity and phylogeographic structure. METHODS AND RESULTS: Using Illumina HiSeq and MiSeq, 15 fungus-specific microsatellite markers were developed and tested on 81 specimens from four populations from Spain. The number of alleles ranged from four to 13 alleles per locus with a mean of 7.9, and average gene diversities varied from 0.40 to 0.73 over four populations. The amplification rates of 10 markers (CA01-CA10) in populations of C. aculeata exceeded 85%. The markers also amplified across a range of closely related species, except for locus CA05, which did not amplify in C. australiensis and C. "panamericana," and locus CA10 which did not amplify in C. australiensis. CONCLUSIONS: The identified microsatellite markers will be used to study the genetic diversity and phylogeographic structure in populations of C. aculeata in western Eurasia. PMID- 27672521 TI - Twenty novel polymorphic microsatellite primers in the critically endangered Melastoma tetramerum var. tetramerum (Melastomataceae). AB - PREMISE OF THE STUDY: Microsatellite markers were identified for Melastoma tetramerum var. tetramerum (Melastomataceae), a critically endangered shrub endemic to the Bonin Islands, to reveal genetic characteristics in wild and restored populations. METHODS AND RESULTS: Using next-generation sequencing, 27 microsatellite markers were identified. Twenty of these markers were polymorphic in M. tetramerum var. tetramerum, with two to nine alleles per locus and expected heterozygosity ranging from 0.10 to 0.71. Among the 20 polymorphic markers, 15 were applicable to other closely related taxa, namely M. tetramerum var. pentapetalum, M. candidum var. candidum, and M. candidum var. alessandrense. CONCLUSIONS: These markers can be potentially useful to investigate the genetic diversity, population genetic structure, and reproductive ecology of M. tetramerum var. tetramerum as well as of the three related taxa to provide appropriate genetic information for conservation. PMID- 27672522 TI - A genomic approach for isolating chloroplast microsatellite markers for Pachyptera kerere (Bignoniaceae). AB - PREMISE OF THE STUDY: In this study, we developed chloroplast microsatellite markers (cpSSRs) for Pachyptera kerere (Bignoniaceae) to investigate the population structure and genetic diversity of this species. METHODS AND RESULTS: We used Illumina HiSeq data to reconstruct the chloroplast genome of P. kerere by a combination of de novo and reference-guided assembly. We then used the chloroplast genome to develop a set of cpSSRs from intergenic regions. Overall, 24 primer pairs were designed, 21 of which amplified successfully and were polymorphic, presenting three to nine alleles per locus. The unbiased haploid diversity per locus varied from 0.207 (Pac28) to 0.817 (Pac04). All but one locus amplified for all other taxa of Pachyptera. CONCLUSIONS: The markers reported here will serve as a basis for studies to assess the genetic structure and phylogeographic history of Pachyptera. PMID- 27672523 TI - Isolation and characterization of microsatellite loci for the endangered wetland plant Adenophora palustris (Campanulaceae). AB - PREMISE OF THE STUDY: Adenophora palustris (Campanulaceae) is an endangered wetland plant species in Japan. Although it is widely distributed in East Asia, only six extant populations are known in Japan, with fewer than 1000 individuals in total. We developed 15 microsatellite markers for this species and confirmed their utility for the closely related species A. triphylla var. japonica. METHODS AND RESULTS: Ten polymorphic loci were characterized for genetic variation within three populations of A. palustris. The number of alleles per locus ranged from four to 15, with an average of 9.3; the expected heterozygosity ranged from 0.48 to 0.89, with an average of 0.74. Nine loci were successfully amplified in A. triphylla var. japonica, and three of these loci showed polymorphism. CONCLUSIONS: These markers are useful for investigating genetic diversity and gene flow within and among remnant populations of A. palustris in Japan, and the results will provide crucial information for conservation. PMID- 27672524 TI - Development of transcriptome-derived SSR markers for Hoya ledongensis (Apocynaceae) and cross-amplification in a congener. AB - PREMISE OF THE STUDY: To examine patterns of genetic diversity and test possible hybridization events, microsatellite markers were identified and characterized in Hoya ledongensis (Apocynaceae), and cross-amplification was tested in a congener, H. jianfenglingensis. METHODS AND RESULTS: Based on the transcriptome data of H. ledongensis, 46 microsatellite primer pairs were randomly selected for initial validation. From these, 28 primer pairs were successfully amplified, 12 of which were polymorphic in 36 individuals across three populations of H. ledongensis. The number of alleles per microsatellite locus ranged from two to 11. The observed and expected heterozygosities for the 12 loci ranged from 0.133 to 0.867 and 0.128 to 0.894, respectively. Cross-species amplification was successful for these 12 loci in the congeneric species H. jianfenglingensis. CONCLUSIONS: These polymorphic transcriptome-derived simple sequence repeat markers have the potential to be used as multilocus molecular markers to study the population genetics and natural hybridization in species of Hoya. PMID- 27672525 TI - The complete chloroplast genome sequences for four Amaranthus species (Amaranthaceae). AB - PREMISE OF THE STUDY: The amaranth genus contains many important grain and weedy species. We further our understanding of the genus through the development of a complete reference chloroplast genome. METHODS AND RESULTS: A high-quality Amaranthus hypochondriacus (Amaranthaceae) chloroplast genome assembly was developed using long-read technology. This reference genome was used to reconstruct the chloroplast genomes for two closely related grain species (A. cruentus and A. caudatus) and their putative progenitor (A. hybridus). The reference genome was 150,518 bp and possesses a circular structure of two inverted repeats (24,352 bp) separated by small (17,941 bp) and large (83,873 bp) single-copy regions; it encodes 111 genes, 72 for proteins. Relative to the reference chloroplast genome, an average of 210 single-nucleotide polymorphisms (SNPs) and 122 insertion/deletion polymorphisms (indels) were identified across the analyzed genomes. CONCLUSIONS: This reference chloroplast genome, along with the reported simple sequence repeats, SNPs, and indels, is an invaluable genetic resource for studying the phylogeny and genetic diversity within the amaranth genus. PMID- 27672526 TI - Autoimmune Schizophrenia? Psychiatric Manifestations of Hashimoto's Encephalitis. AB - Hashimoto's encephalitis (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), can be a debilitating manifestation of an autoimmune reaction against the thyroid that is often under diagnosed primarily due to a lack of definitive diagnostic criteria. This is a case of a 52-year-old woman who has been diagnosed with HE after presenting with recurrent and severe psychosis in conjunction with paranoia and a thyroidopathy. Her symptoms are chronic, having first been documented as presenting 15 years prior and showing progressive exacerbation in both frequency and severity. The patient's paranoia often manifested as delusions involving family members or close friends and consequently introduced an opportunity for harm to herself and others. She showed great conviction with self-diagnoses that were proven incorrect, resulting in occasional non-compliance. Between episodes, the patient did not show evidence of symptoms. This patient struggled with several incorrect diagnoses and treatments for several years before the correct diagnosis of HE was made and displayed extreme improvement upon corticosteroid administration. This case illustrates the importance of increasing awareness of HE as well as including HE in a differential diagnosis when any patient presents with psychosis and concurrent thyroidopathy. Hashimoto's encephalitis follows putative characteristics of autoimmune diseases, exhibiting a higher incidence in women as compared to men, presenting with increased titers of autoantibodies, and showing dramatic amelioration when treated with corticosteroids. PMID- 27672527 TI - Is there a link between Depressive Disorders and Tryptophan Hydroxylase 1 (TPH1) Gene Polymorphism? - Study from a Distressed Area, Kashmir (India). AB - BACKGROUND: The progress that man has made in all domains of life, during all these years of reign over the earth, is utterly remarkable. However, it always came at a price. Each epoch of progress has seen human beings inflicted with trauma and cynical consequences. During the last two decades, Kashmiri (Indian) people have experienced continuous violence, a reign of terror, and political turmoil. Each of these disastrous events has contributed to the increase in psychiatric disorders in this part of the world, especially major depressive disorders. We can observe that besides the environmental influences, gene polymorphism also plays a crucial role in the development of depressive disorders. The role of Tryptophan Hydroxylase 1 (TPH1) gene is implicated in various psychiatric disorders, including depression. However, no study has investigated TPH1 A779C gene polymorphism in depressive disorders in a distressed society like Kashmir (India). AIMS: To study TPH1 A779C single nucleotide polymorphism in depressive disorders in Kashmiri (Indian) population. MATERIALS AND METHODS: Two hundred and forty patients diagnosed with depressive disorder, and 160 unrelated healthy volunteers (control), were studied in a case-control study design. Polymorphism was determined using polymerase chain reaction (PCR) and agarose gel electrophoresis, after digestion with HAP II enzyme. Genotypes and allele frequencies were compared using Chi-square tests, Fisher's exact test, odds ratio, 95% confidence interval (C.I.) and a p-value of <0.05 was considered to be statistically significant. RESULTS: The mean age +/- standard deviation (SD) of depression and control group was 32.02+/-10.99 and 31.75+/-9.93, respectively (p= 0.512). It was found that the patients from depression group had AA genotype (51.7%) in comparison to control group (17.5%) and these results were statistically significant (p<=0.0001). Calculation of allelic frequency revealed a stronger association of A allele with depression group (70.83%) than with the control group (41.25%), and it was also found to be statistically significant (p<=0.0001) with C.I. of 3.459 (1.909-6.266). CONCLUSION: TPH1 A779C A gene was found to be associated with a major depressive disorder (MDD) in Kashmiri (Indian) population. There were high HAM-A as well as HAM-D scores in depressive patients of Kashmir (India). PMID- 27672528 TI - A Unique Case of Intracranial Mucormycosis Following an Assault. AB - Intracranial mucormycosis is a very unusual presentation of an infection after a depressed skull fracture due to an assault. Only sporadic cases have been reported in the literature previously. A 30-year-old male with a traumatic brain injury following an assault, status-post debridement and elevation of a depressed skull fracture, was discharged home several weeks postoperatively. A CT scan of the head with contrast was obtained due to mental status changes and revealed an enhancing ring-shaped lesion in the right frontal lobe consistent with a brain abscess. The patient was taken to the operating room for image-guided excisional biopsy of the lesion, with pathology revealing mucormycosis. PMID- 27672529 TI - Intravascular Ultrasound for Intracranial and Extracranial Carotid Artery Stent Placement. AB - Intravascular ultrasound (IVUS) can provide valuable information regarding endoluminal morphology. We present the first description of IVUS-guided intracranial and extracranial carotid artery stent placement for arterial dissection. A 41-year-old female with a sudden-onset headache and blurred vision underwent a computed tomography (CT) angiogram imaging that revealed bilateral carotid artery dissections (BCAD) and a left vertebral artery dissection (VAD). Endovascular treatment (EVT) of a long segment right carotid artery dissection (CAD) was performed employing two Carotid WALLSTENTTM MonorailsTM (8 x 36 mm, 10 x 31 mm) (Boston Scientific, Marlborough, MA). With the help of the IVUS, the distal stent was placed up to the petrous carotid artery, followed by the placement of the second stent in the immediate proximal location with some overlap that extended down to the carotid artery bulb. Intraoperative angiography and post-stenting IVUS revealed excellent stent placement with good resolution of the dissection and good luminal patency with pseudolumen obliteration. Stent use for intracranial circulation dissections will continue to be a favorable option given the decreased morbidity of endovascular therapy in this location. As endovascular surgeons become more facile with the use of IVUS, using it as a guide for stent placement and post-stenting confirmation will help them to ensure proper positioning and improved patency rates. PMID- 27672530 TI - Adapting to a US Medical Curriculum in Malaysia: A Qualitative Study on Cultural Dissonance in International Education. AB - CONTEXT: Minimal research has examined the recent exportation of medical curricula to international settings. Johns Hopkins University School of Medicine in Baltimore, USA partnered with Perdana University Graduate School of Medicine in Kuala Lumpur, Malaysia and implemented the same curriculum currently used at Johns Hopkins University to teach medical students at Perdana University. This study aimed to explore the perspectives of first-year medical students at Perdana University, focusing on issues of cultural dissonance during adaptation to a US curriculum. METHODS: In-depth semi-structured interviews with the inaugural class of first-year students (n=24) were conducted, audio-recorded, and transcribed. Two reviewers independently coded and analyzed the qualitative data for major themes. RESULTS: The most prominent themes identified were the transition from a "passive" to an "active" learning environment and the friendliness and openness of the professors. Students noted that "[Perdana University] is a whole new, different culture and now we are adapting to the culture." Being vocal during classes and taking exams based on conceptual understanding and knowledge application/integration proved to be more challenging for students than having classes taught entirely in English or the amount of material covered. DISCUSSION: This study reinforced many cultural education theories as it revealed the major issues of Malaysian graduate students adapting to a US-style medical curriculum. Despite coming from a collectivistic, Confucian-based cultural learning background, the Malaysian students at Perdana University adopted and adapted to, and subsequently supported, the US learning expectations. PMID- 27672531 TI - Late Spontaneous Migration of a Dorsal Column Stimulator Paddle Lead. AB - The most frequently encountered complication of dorsal column stimulators is lead migration. The vast majority of these events are seen in the first few weeks to months. Late paddle lead migration is a very uncommon occurrence in this setting. We describe a case of a 51-year-old male with a history of reflex sympathetic dystrophy having undergone dorsal column stimulator insertion at the level of C1 C2. A good clinical benefit was appreciated in the postoperative period once the stimulator was turned on. Approximately six months postoperatively, the patient suddenly lost coverage. Radiographic imaging revealed that the lead had migrated caudally to the C3-C4 level. Subsequent revision surgery took place. This description highlights a common complication, but occurring outside the expected time frame after surgery. PMID- 27672532 TI - Research in Medical School: A Survey Evaluating Why Medical Students Take Research Years. AB - INTRODUCTION: In recent years, an increasing number of medical students have taken time off during medical school in order to conduct research. Schools and students have invested millions of dollars and thousands of person-years on research projects, but little is known as to why students choose to take this time off. We aim to characterize why students take research years during medical school. METHODS: The authors distributed an online survey about research in medical school to students at five medical schools that have highly regarded research programs. RESULTS: 328 students responded to the survey. The most common reasons students take years off for research are: "increase competitiveness for residency application" (32%), "time to pursue other opportunities" (24%), and "academic interest" (23%). Students who would still take a research year even if they were already assured a position in a residency program of their choice were at 65%, while 35% would not take a research year. Responses varied based on whether students intended to go into a competitive specialty. DISCUSSION: Medical students take research years for multiple reasons, although they frequently are not motivated by an interest in the research itself. Many student projects consume a substantial amount of time and money despite having little educational value. Medical schools, residency programs, and policymakers should rethink incentives to increase value and help students better pursue their academic interests. PMID- 27672533 TI - Reconstruction of the Odontoid Process by a Tricortical Iliac Crest Graft in a Case of Tuberculosis of C1, C2, and C3 Vertebrae. AB - Tuberculosis (TB) is an emerging disease which affects about one-third of the world's population, especially in developing countries. TB of the spine is the most common type of skeletal TB. Cervical spine TB is rare, constituting 2-3% of all cases of spinal TB. We would like to present an unusual case of tuberculosis of the C1, C2, and C3 vertebrae with neurological deficit and its difficult management. A new method of treatment was done for this patient, which included reconstruction of the odontoid process using a tricortical iliac crest graft that was fixed with an anterior cervical plate. On follow-up, there was good incorporation of the graft. The neurological condition of the patient improved and was normal with partial restriction of neck movements. We suggest this technique to be worthwhile for treatment of this disease at this location. PMID- 27672534 TI - Post-Traumatic, Drug-Resistant Epilepsy and Review of Seizure Control Outcomes from Blinded, Randomized Controlled Trials of Brain Stimulation Treatments for Drug-Resistant Epilepsy. AB - BACKGROUND: Many post-traumatic epilepsy (PTE) patients become resistant to medications. Nervous stimulation as a treatment for drug-resistant epilepsy (DRE) is an active area of clinical investigation. OBJECTIVE: To summarize methods, reported seizure control outcome measures, and adverse events from blinded, randomized control trials (RCTs) for selected invasive brain stimulation (IBS) and non-invasive brain stimulation (NIBS) treatment options in patients with DRE. METHODS: PubMed was searched for articles from 1995-2014, using search terms related to the topics of interest. Available relevant articles reporting the outcomes of interest were identified and data was extracted. Articles in the reference lists of relevant articles and clinicaltrials.gov were also referenced. RESULTS: Eleven articles were analyzed with a total of 795 patients identified. Studies showed that select nervous stimulation treatments significantly reduced seizure frequency in patients with DRE. PMID- 27672535 TI - Urban Enhancement of PM10 Bioaerosol Tracers Relative to Background Locations in the Midwestern United States. AB - Bioaerosols are well-known immune-active particles that exacerbate respiratory diseases. Human exposures to bioaerosols and their resultant health impacts depend on their ambient concentrations, seasonal and spatial variation, and co pollutants, which are not yet widely characterized. In this study, chemical and biological tracers of bioaerosols were quantified in respirable particulate matter (PM10) collected at three urban and three background sites in the Midwestern United States across four seasons in 2012. Endotoxins from gram negative bacteria (and a few gram positive bacteria), water-soluble proteins, and tracers for fungal spores (fungal glucans, arabitol and mannitol) were ubiquitous and showed significant seasonal variation and dependence on temperature. Fungal spores were elevated in spring and peaked in summer, following the seasonal growing cycle, while endotoxins peaked in autumn during the row crop harvesting season. Paired comparisons of bioaerosols in urban and background sites revealed significant urban enhancements in PM10, fungal glucans, endotoxins and water soluble proteins relative to background locations, such that urban populations have a greater outdoor exposure to bioaerosols. These bioaerosols contribute, in part, to the urban excesses in PM10. Higher bioaerosol mass fractions in urban areas relative to background sites indicate that urban areas serve as a source of bioaerosols. Similar urban enhancements in water-soluble calcium and its correlation with bioaerosol tracers point towards wind-blown soil as an important source of bioaerosols in urban areas. PMID- 27672536 TI - Next generation sequencing: Coping with rare genetic diseases in China. AB - With a population of 1.4 billion, China shares the largest burden of rare genetic diseases worldwide. Current estimates suggest that there are over ten million individuals afflicted with chromosome disease syndromes and well over one million individuals with monogenic disease. Care of patients with rare genetic diseases remains a largely unmet need due to the paucity of available and affordable treatments. Over recent years, there is increasing recognition of the need for affirmative action by government, health providers, clinicians and patients. The advent of new next generation sequencing (NGS) technologies such as whole genome/exome sequencing, offers an unprecedented opportunity to provide large scale population screening of the Chinese population to identify the molecular causes of rare genetic diseases. As a surrogate for lack of effective treatments, recent development and implementation of noninvasive prenatal testing (NIPT) in China has the greatest potential, as a single technology, for reducing the number of children born with rare genetic diseases. PMID- 27672537 TI - Fragile X syndrome: A review of clinical management. AB - The fragile X mental retardation 1 gene, which codes for the fragile X mental retardation 1 protein, usually has 5 to 40 CGG repeats in the 5' untranslated promoter. The full mutation is the almost always the cause of fragile X syndrome (FXS). The prevalence of FXS is about 1 in 4,000 to 1 in 7,000 in the general population although the prevalence varies in different regions of the world. FXS is the most common inherited cause of intellectual disability and autism. The understanding of the neurobiology of FXS has led to many targeted treatments, but none have cured this disorder. The treatment of the medical problems and associated behaviors remain the most useful intervention for children with FXS. In this review, we focus on the non-pharmacological and pharmacological management of medical and behavioral problems associated with FXS as well as current recommendations for follow-up and surveillance. PMID- 27672539 TI - Targeting mRNA for the treatment of facioscapulohumeral muscular dystrophy. AB - Facioscapulohumeral muscular dystrophy (FSHD) is an inherited autosomal dominant disorder characterized clinically by progressive muscle degeneration. Currently, no curative treatment for this disorder exists. FSHD patients are managed through physiotherapy to improve function and quality of life. Over the last two decades, FSHD has been better understood as a disease genetically characterized by a pathogenic contraction of a subset of macrosatellite repeats on chromosome 4. Specifically, several studies support an FSHD pathogenesis model involving the aberrant expression of the double homeobox protein 4 (DUX4) gene. Hence, potential therapies revolving around inhibition of DUX4 have been explored. One of the potential treatment options is the use of effective antisense oligonucleotides (AOs) to knockdown expression of the myopathic DUX4 gene and its downstream molecules including paired-like homeodomain transcription factor 1 (PITX1). Success in the suppression of PITX1 expression has already been demonstrated systemically in vivo in recent studies. In this article, we will review the pathogenesis of FSHD and the latest research involving the use of antisense knockdown therapy. PMID- 27672540 TI - Endocarditis in left ventricular assist device. AB - Heart failure is one of the leading causes of death in developed nations. End stage heart failure often requires cardiac transplantation for survival. The left ventricular assist device (LVAD) has been one of the biggest evolvements in heart failure management often serving as bridge to transplant or destination therapy in advanced heart failure. Like any other medical device, LVAD is associated with complications with infections being reported in many patients. Endocarditis developing secondary to the placement of LVAD is not a frequent, serious and difficult to treat condition with high morbidity and mortality. Currently, there are few retrospective studies and case reports reporting the same. In our review, we found the most common cause of endocarditis in LVAD was due to bacteria. Both bacterial and fungal endocarditis were associated with high morbidity and mortality. In this review we will be discussing the risk factors, organisms involved, diagnostic tests, management strategies, complications, and outcomes in patients who developed endocarditis secondary to LVAD placement. PMID- 27672538 TI - Review of targeted treatments in fragile X syndrome. AB - Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the leading single-gene cause of autism spectrum disorders. It is due to a loss of the fragile X mental retardation protein, which leads to molecular, behavioral, and cognitive deficits in these patients. Improvements in our understanding of its pathophysiology have led to the development of numerous targeted treatments in FXS as highlighted by metabotropic glutamate receptor antagonists and gamma-Aminobutyric acid receptor modulators. This review will summarize relevant pre-clinical data and results from clinical trials in human subjects with FXS. It will also highlight upcoming studies and future directions for clinical trials as well. PMID- 27672541 TI - Development of chidamide for peripheral T-cell lymphoma, the first orphan drug approved in China. AB - Peripheral T-cell lymphoma (PTCL) is a set of rare and highly heterogeneous group of mature T- and NK-cell neoplasms associated with poor outcomes and lack of standard and effective therapies. The total number of newly diagnosed cases of PTCL yearly in China is estimated about 50,000. Chidamide (CS055) is a novel and orally active benzamide class of histone deacetylase (HDAC) inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, the enzymes that are involved and play an important role in tumor initiation and development in both tumor cells and their surrounding micro-environment. Functioning as a genuine epigenetic modulator, chidamide induces growth arrest and apoptosis in tumor cells and enhances cellular antitumor immunity. Based on the overall results from preclinical and phase I clinical studies, exploratory and pivotal phase II trials of chidamide for relapsed or refractory PTCL were conducted from March 2009 to May 2012, and the results led to CFDA approval of chidamide for the indication in December 2014, being the first approved orphan drug according to the research & development approach of orphan drugs in China, as well as the first orally active drug for PTCL in China and worldwide. PMID- 27672543 TI - Perceptions regarding a range of work-related issues and corresponding support needs of individuals with an intractable disease. AB - A number of persons with an intractable disease (ID) experience work-related problems that could lead to job loss. The aim of this study was to ascertain perceptions regarding a range of work-related issues and corresponding support needs of individuals with an ID. Potential participants were people ages 15 to 64 with one of the 130 intractable chronic diseases designated in the Act to Comprehensively Support the Daily and Social Activities of Persons with Disabilities (Comprehensive Support for the Disabled Act). Participants completed a self-administered questionnaire. With the assistance of patients' organizations, 3,000 questionnaires were mailed to potential participants. Questions included demographic characteristics, family concerns, employment/supported employment, work accommodations, and other aspects of life. Responses were received from 889 (29.6%) participants, and respondents had 57 IDs. Forty-six-point-seven percent of respondents reported being unemployed due to fatigue and/or long-term treatment. Nearly half of the unemployed respondents reported that they had been unable to work despite their willingness to do so. Common requests for accommodation included flexible work hours, working at home, and job/workplace modifications. Only 30% of respondents knew about job training programs and supported work available for persons with disabilities. The results of the study are relevant for employees, employers, and occupational health/human resource professionals. The issue of reasonable accommodations for persons with an ID needs to be addressed in future research in order to promote continued work by those persons. PMID- 27672542 TI - Urine-derived induced pluripotent stem cells as a modeling tool to study rare human diseases. AB - Rare diseases with a low prevalence are a key public health issue because the causes of those diseases are difficult to determine and those diseases lack a clearly established or curative treatment. Thus, investigating the molecular mechanisms that underlie the pathology of rare diseases and facilitating the development of novel therapies using disease models is crucial. Human induced pluripotent stem cells (iPSCs) are well suited to modeling rare diseases since they have the capacity for self-renewal and pluripotency. In addition, iPSC technology provides a valuable tool to generate patient-specific iPSCs. These cells can be differentiated into cell types that have been affected by a disease. These cells would circumvent ethical concerns and avoid immunological rejection, so they could be used in cell replacement therapy or regenerative medicine. To date, human iPSCs could have been generated from multiple donor sources, such as skin, adipose tissue, and peripheral blood. However, these cells are obtained via invasive procedures. In contrast, several groups of researchers have found that urine may be a better source for producing iPSCs from normal individuals or patients. This review discusses urinary iPSC (UiPSC) as a candidate for modeling rare diseases. Cells obtained from urine have overwhelming advantages compared to other donor sources since they are safely, affordably, and frequently obtained and they are readily obtained from patients. The use of iPSC-based models is also discussed. UiPSCs may prove to be a key means of modeling rare diseases and they may facilitate the treatment of those diseases in the future. PMID- 27672544 TI - Alcohol use dependence in fragile X syndrome. AB - Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID- 27672545 TI - Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome. AB - Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by impaired thyroid hormone transporter. Patients with AHDS usually exhibit severe motor developmental delay, delayed myelination of the brain white matter, and elevated T3 levels in thyroid tests. Neurological examination of two patients with neurodevelopmental delay revealed generalized hypotonia, and not paresis, as the main neurological finding. Nystagmus and dyskinesia were not observed. Brain magnetic resonance imaging demonstrated delayed myelination in early childhood in both patients. Nevertheless, matured myelination was observed at 6 years of age in one patient. Although the key finding for AHDS is elevated free T3, one of the patients showed a normal T3 level in childhood, misleading the diagnosis of AHDS. Genetic analysis revealed two novel SLC16A2 mutations, p.(Gly122Val) and p.(Gly221Ser), confirming the AHDS diagnosis. These results indicate that AHDS diagnosis is sometimes challenging owing to clinical variability among patients. PMID- 27672546 TI - Malignant McKittrick-Wheelock syndrome as a cause of acute kidney injury and hypokalemia: Report of a case and review of literature. AB - Colonic polyps are usually asymptomatic, and are commonly detected during screening colonoscopy. Severe hypokalemia secondary to secretory diarrhea is a rare presentation of rectal polyps. We present a 70 years old female with hypokalemia and acute kidney injury secondary to secretory diarhea due to moderately differentiated adenocarcinoma of rectum, all of which is syndromically sometimes referred to as McKittrick and Wheelock syndrome. The case is presented because McKittrick-Wheelock syndrome is still more uncommon with malignancy. The syndrome may be associated with other features of hypersecretory diarrhea. Though very rare, clinical suspicion would often lead to diagnosis and appropriate management. We also review the previously published reports of this entity. PMID- 27672547 TI - Coffin-Siris syndrome with cafe-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene. AB - Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, cafe-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better. PMID- 27672548 TI - Hemophagocytic lymphohistiocytosis: A rare cause of recurrent encephalopathy. AB - We report an unusual case of recurrent encephalopathy due to acquired hemophagocytic lymphohistiocytosis (HLH) in a patient with propionic acidemia (PA). PA is an inherited metabolic disorder in which patients often present with encephalopathy and pancytopenia during metabolic decompensation. However, these patients may rarely develop HLH with similar presentation. This case illustrates the need to distinguish HLH induced encephalopathy from the one secondary to metabolic decompensation in these patients, as early diagnosis and treatment of HLH improves prognosis. This case also highlights the importance of considering HLH in patients presenting with unexplained encephalopathy, as early diagnosis and treatment is lifesaving in this otherwise lethal condition. To our knowledge this is the first case report of acquired HLH presenting as recurrent encephalopathy followed by complete recovery, in a metabolically stable patient with PA. PMID- 27672550 TI - Behavioral phenotype in a child with Prader-Willi syndrome and comorbid 47, XYY. AB - We report a 12-year-old male with Prader-Willi syndrome (PWS) and 47, XYY syndrome. Genetic work up revealed 47, XYY karyotype. PWS diagnosis was made by polymerase chain reaction methylation and maternal uniparental disomy (mUPD) was determined to be the etiology. Review of distinct behavioral features, possible interplay between the two syndromes and considerations for diagnoses are presented. To our knowledge, this is the first report of behavioral features in PWS with comorbid 47, XYY. PMID- 27672549 TI - Cystic adventitial disease of the common femoral vein: A case report. AB - Adventitial cystic disease (ACD) of the common femoral vein is a rare vascular disorder. It becomes more difficult to recognize preoperatively especially when the femoral vein is affected. We report the case of a 62-year-old female patient who presented with a one-month history of painless swelling in her right lower extremity. She had no specific past medical history and no history of trauma, and had a full coagulopathy profile that was negative for any hypercoagulable syndrome. On examination, her lower right leg was significantly swollen with a palpable mass in her right inguinal region. A computerized tomography (CT) with contrast was performed to provide more information and revealed an eccentric compression over the medial wall of the right common femoral vein. During surgical exploration, adventitial cystic mucinous disease was enucleated and the patient underwent femoral exploration, excision of the cysts and reconstruction of iliac femoral vein graft using an artificial blood vessel. The pathological examination confirmed the diagnosis. The patient continued to do well, and she had an unremarkable venous duplex evaluation at her 6-month follow-up. The presentation, investigation, treatment, and pathology of this condition are discussed with a literature review. PMID- 27672552 TI - Retroperitoneal fibrosis with periaortitis: A case report of an unusual form of presentation of granulomatosis with polyangiitis. AB - Granulomatosis with polyangiitis (GPA) is the name that has been used in recent years for Wegener's granulomatosis. This condition is a systemic inflammatory disease characterised by necrotizing vasculitis that affects small and medium sized blood vessels (capillaries, arterioles, venules and arteries). The granulomatous inflammation affects the respiratory system; it also commonly affects the kidney and can very rarely affect large vessels such as the aorta and the surrounding retroperitoneal tissue. Early diagnosis and treatment is of vital importance because of the high risk of dissection and of obstruction of retroperitoneal structures. We present the case of a 74-year-old man with a past history of infrarenal abdominal aortic aneurysm. He consulted for abdominal pain. Cavitating pulmonary nodules and retroperitoneal fibrosis with periaortic alterations were detected on computed tomography. Laboratory investigations revealed that the patient was positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and necrotizing granulomas were observed on biopsies of the lung lesions and retroperitoneal tissue. The patient was diagnosed with GPA and treatment was started with glucocorticoids and immunosuppressive agents, which led to a significant clinical and radiological improvement over the following months. PMID- 27672551 TI - Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource Limited Settings. AB - Fungal diseases are an important cause of mortality in immunocompromised hosts, and their incidence in pediatric cancer patients in low- to middle-income countries is underestimated. In this review, we present relevant, up-to-date information about the most common opportunistic and endemic fungal diseases among children with cancer, their geographic distribution, and recommended diagnostics and treatment. Efforts to improve the care of children with cancer and fungal disease must address the urgent need for sustainable and cost-effective solutions that improve training, fungal disease testing capability, and the use of available resources. We hope that the collective information presented here will be used to advise healthcare providers, regional and country health leaders, and policymakers of the current challenges in diagnosing and treating fungal infections in children with cancer in low- to middle-income countries. PMID- 27672553 TI - A rare cause of cavitatory pneumonia. AB - Radiographic findings of thick walled cavities in the lungs are typically seen in mycobacterial infections, malignant lesions, fungal infections, pulmonary vasculitis or other inflammatory lesions of the lungs. Necrotizing infections of the lungs caused by gram negative bacteria (Klebsiella, Psudomonas, Legionella) and Staphylococcus aureus may also form cavities of varying thickness, with consolidation. Escherichia coli pneumonia causing pulmonary cavities is very rare and the few cases reported are of pneumatocele formation. Here we present an unusual case of Escherichia coli infection as a rare cause of bilateral cavitating necrotizing pneumoniae, in a 67 year old male with uncontrolled type 2 diabetes mellitus. PMID- 27672554 TI - Alpha oscillation neurofeedback modulates amygdala complex connectivity and arousal in posttraumatic stress disorder. AB - OBJECTIVE: Electroencephalogram (EEG) neurofeedback aimed at reducing the amplitude of the alpha-rhythm has been shown to alter neural networks associated with posttraumatic stress disorder (PTSD), leading to symptom alleviation. Critically, the amygdala is thought to be one of the central brain regions mediating PTSD symptoms. In the current study, we compare directly patterns of amygdala complex connectivity using fMRI, before and after EEG neurofeedback, in order to observe subcortical mechanisms associated with behavioural and alpha oscillatory changes among patients. METHOD: We examined basolateral (BLA), centromedial (CMA), and superficial (SFA) amygdala complex resting-state functional connectivity using a seed-based approach via SPM Anatomy Toolbox. Amygdala complex connectivity was measured in twenty-one individuals with PTSD, before and after a 30-minute session of EEG neurofeedback targeting alpha desynchronization. RESULTS: EEG neurofeedback was associated with a shift in amygdala complex connectivity from areas implicated in defensive, emotional, and fear processing/memory retrieval (left BLA and left SFA to the periaqueductal gray, and left SFA to the left hippocampus) to prefrontal areas implicated in emotion regulation/modulation (right CMA to the medial prefrontal cortex). This shift in amygdala complex connectivity was associated with reduced arousal, greater resting alpha synchronization, and was negatively correlated to PTSD symptom severity. CONCLUSION: These findings have significant implications for developing targeted non-invasive treatment interventions for PTSD patients that utilize alpha oscillatory neurofeedback, showing evidence of neuronal reconfiguration between areas highly implicated in the disorder, in addition to acute symptom alleviation. PMID- 27672555 TI - Disorder-specific characteristics of borderline personality disorder with co occurring depression and its comparison with major depression: An fMRI study with emotional interference task. AB - Borderline personality disorder (BPD) and major depressive disorder (MDD) are both associated with abnormalities in the regulation of emotion, with BPD being highly comorbid with MDD. Disorder-specific dysfunctions in BPD, however, have hardly been addressed, hence the lack of knowledge pertaining to the specificity of emotion processing deficits and their commonality with MDD. 24 healthy comparison subjects, 21 patients with MDD, and 13 patients with comorbid BPD and MDD (BPD + MDD group) were studied using functional MRI. The subjects were required to perform an emotional interference task that entailed categorizing facial affect while ignoring words that labeled the emotional contents of the external stimuli. Collapsing across emotional face types, we observed that participants with BPD + MDD uniquely displayed a greater involvement of the visual areas and the cerebellum. During emotional conflict processing, on the other hand, the lateral prefrontal cortex (LPFC) appeared to be affected in both patient groups. In comparison to the HC, the MDD group showed differences also in the posterior medial frontal cortex (pMFC) and the inferior parietal lobule (IPL). Thus, our data indicate dysfunctionality in the neural circuitry responsible for emotional conflict control in both disorders. The enhanced visual cortex activation in BPD + MDD suggests the visual system's hyperresponsiveness to faces at an early perceptual level. Not being associated with co-occurring depression, this effect in BPD + MDD appears to represent specific personality traits such as disturbed reactivity toward emotionally expressive facial stimuli. PMID- 27672556 TI - Quantitative magnetic resonance imaging traits as endophenotypes for genetic mapping in epilepsy. AB - Over the last decade, the field of imaging genomics has combined high-throughput genotype data with quantitative magnetic resonance imaging (QMRI) measures to identify genes associated with brain structure, cognition, and several brain related disorders. Despite its successful application in different psychiatric and neurological disorders, the field has yet to be advanced in epilepsy. In this article we examine the relevance of imaging genomics for future genetic studies in epilepsy from three perspectives. First, we discuss prior genome-wide genetic mapping efforts in epilepsy, considering the possibility that some studies may have been constrained by inherent theoretical and methodological limitations of the genome-wide association study (GWAS) method. Second, we offer a brief overview of the imaging genomics paradigm, from its original inception, to its role in the discovery of important risk genes in a number of brain-related disorders, and its successful application in large-scale multinational research networks. Third, we provide a comprehensive review of past studies that have explored the eligibility of brain QMRI traits as endophenotypes for epilepsy. While the breadth of studies exploring QMRI-derived endophenotypes in epilepsy remains narrow, robust syndrome-specific neuroanatomical QMRI traits have the potential to serve as accessible and relevant intermediate phenotypes for future genetic mapping efforts in epilepsy. PMID- 27672558 TI - Brain development in adolescents at ultra-high risk for psychosis: Longitudinal changes related to resilience. AB - BACKGROUND: The main focus of studies of individuals at ultra-high risk for psychosis (UHR) has been on identifying brain changes in those individuals who will develop psychosis. However, longitudinal studies have shown that up to half of UHR individuals are resilient, with symptomatic remission and good functioning at follow-up. Yet little is known about brain development in resilient individuals. Therefore, the aim of this study was to investigate differences in brain development between resilient and non-resilient individuals. METHODS: A six year longitudinal structural MRI study was performed with up to three scans per individual. The final sample consisted of 48 UHR individuals and 48 typically developing controls with a total of 225 MRI-scans, aged 12-20 years at the time of the first MRI-scan and matched for age, gender and number of follow-up scans. At six-year follow-up, 35 UHR individuals were divided in resilient (good functional outcome) and non-resilient (poor functional outcome) subgroups, defined by the modified Global Assessment of Functioning. The main outcome measures were developmental changes in MR-based measures of cortical and subcortical anatomy. RESULTS: We found widespread differences in volume of frontal, temporal and parietal cortex between resilient and non-resilient individuals. These were already present at baseline and remained stable over development (12-24 years). Furthermore, there were differences in the development of cortical surface area in frontal regions including cingulate gyrus. CONCLUSIONS: Developmental differences may reflect compensatory neural mechanisms, where better functioning in resilient individuals leads to less tissue loss over development. PMID- 27672557 TI - Cognitive Slowing in Gulf War Illness Predicts Executive Network Hyperconnectivity: Study in a Population-Representative Sample. AB - Cognitive slowing is a prevalent symptom observed in Gulf War Illness (GWI). The present study assessed the extent to which functional connectivity between dorsolateral prefrontal cortex (DLPFC) and other task-relevant brain regions was predictive of GWI-related cognitive slowing. GWI patients (n = 54) and healthy veteran controls (n = 29) were assessed on performance of a processing speed task (the Digit Symbol Substitution Task; DSST) while undergoing functional magnetic resonance imaging (fMRI). GWI patients were slower on the DSST relative to controls. Bilateral DLPFC connectivity with task-relevant nodes was altered in GWI patients compared to healthy controls during DSST performance. Moreover, hyperconnectivity in these networks predicted GWI-related increases in reaction time on the DSST, whereas hypoconnectivity did not. These results suggest that GWI-related cognitive slowing reflects reduced efficiency in cortical networks. PMID- 27672560 TI - Genome wide binding (ChIP-Seq) of murine Bapx1 and Sox9 proteins in vivo and in vitro. AB - This work pertains to GEO submission GSE36672, in vivo and in vitro genome wide binding (ChIP-Seq) of Bapx1/Nkx3.2 and Sox9 proteins. We have previously shown that data from a genome wide binding assay combined with transcriptional profiling is an insightful means to divulge the mechanisms directing cell type specification and the generation of tissues and subsequent organs [1]. Our earlier work identified the role of the DNA-binding homeodomain containing protein Bapx1/Nkx3.2 in midgestation murine embryos. Microarray analysis of EGFP tagged cells (both wildtype and null) was integrated using ChIP-Seq analysis of Bapx1/Nkx3.2 and Sox9 DNA-binding proteins in living tissue. PMID- 27672559 TI - Behavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8. AB - This study investigates effects of dipeptide balenine, as a major component of whale meat extract (hereafter, WME), supplementation on senescence-accelerated mouse prone 8 (SAMP8), an Alzheimer's disease (AD) model at level of learning and memory formation and brain expression profiles genome-wide in brain. Mice fed experimental balenine (+ WME) supplemented diet for 26 weeks were subjected to four behavioral tests - open field, Y-maze, new object recognition, and water filled multiple T-maze - to examine effects on learning and memory. Brain transcriptome of SAMP8 mice-fed the WME diet over control low-safflower oil (LSO) diet-fed mice was delineated on a 4 * 44 K mouse whole genome DNA microarray chip. Results revealed the WME diet not only induced improvements in the learning and memory formation but also positively modulated changes in the brain of the SAMP8 mouse; the gene inventories are publically available for analysis by the scientific community. Interestingly, the SAMP8 mouse model presented many genetic characteristics of AD, and numerous novel molecules (Slc2a5, Treh, Fbp1, Aldob, Ppp1r1a, DNase1, Agxt2l1, Cyp2e1, Acsm1, Acsm2, and Pah) were revealed over the SAMR1 (senescence-accelerated mouse resistant 1) mouse, to be oppositely regulated/recovered under the balenine (+ WME) supplemented diet regime by DNA microarray and bioinformatics analyses. Our present study demonstrates an experimental strategy to understand the effects of dipeptide balenine, prominetly contained in meat diet, on SAMP8, providing new insight into whole brain transcriptome changes genome-wide. The gene expression data has been deposited into the Gene Expression Omnibus (GEO): GSE76459. The data will be a valuable resource in examining the effects of natural products, and which could also serve as a human model for further functional analysis and investigation. PMID- 27672561 TI - Changes in bicycling over time associated with a new bike lane: relations with kilocalories energy expenditure and body mass index. AB - Although bicycling has been related to positive health indicators, few studies examine health-related measures associated with non-competitive community cycling before and after cycling infrastructure improvements. This study examined cycling changes in a neighborhood receiving a bike lane, light rail, and other "complete street" improvements. Participants wore accelerometers and global positioning system (GPS) data loggers for one week in both 2012 and 2013, pre- and post- construction completion. Participants sampled within 2 km of the complete street improvements had the following patterns of cycling: never cyclists (n=434), continuing cyclists (n= 29), former cyclists (n=33, who bicycled in 2012 but not 2013), and new cyclists (n=40, who bicycled in 2013 but not 2012). Results show that all three cycling groups, as identified by GPS/accelerometry data, expended more estimated kilocalories (kcal) of energy per minute during the monitoring week than those who were never detected cycling, net of control variables. Similar but attenuated results emerged when cycling self-report measures were used. BMI was not related to cycling group but those who cycled longer on the new path had lower BMI. Although cyclists burn more calories than non-cyclists across the week, among cyclists, their cycling days involved more calories expended than their non-cycling days. The new cyclists account for 39% of the cyclists identified in this study and former cyclists account for 32% of cyclists. These results suggest that cycling is healthy, but that sustaining rates of cycling will be an important goal for future policy and research. PMID- 27672562 TI - Aseptic abscess syndrome associated with traveler's diarrhea after a trip to Malaysia. AB - The first, to our knowledge, case of the aseptic abscesses syndrome as a complication of traveler's diarrhea after a trip to Malaysia is presented. The patient failed to respond to several antimicrobials. The diagnosis was histologically confirmed and the patient only responded to immunomodulatory therapy with corticosteroids and methotrexate. Travel physicians should be aware of this entity reviewed herein in the context of traveler's diarrhea. PMID- 27672563 TI - First description of herpes simplex virus type 1 epididymo-orchitis: A new clinical form of herpes simplex virus infection during septic shock? AB - Genital herpes is increasingly caused by herpes simplex virus type 1 (HSV-1), but recurrences are less frequent than with HSV-2. Distinguishing between primary genital infection and reactivation can be difficult, but HSV-1 more often causes severe primary infections and fewer recurrences. However, as virus reactivation is common during septic shock, a severe form of HSV-1 reactivation can occur in locations other than the lungs, which remain the most common site. The case of a 79-year-old Caucasian man who presented with HSV-1 epididymo-orchitis after three episodes of severe sepsis or septic shock in the context of acute biliary necrotizing pancreatitis is described. This is the first reported case of HSV-1 epididymo-orchitis due to virus reactivation during sepsis. PMID- 27672564 TI - Return to sports after shoulder arthroplasty. AB - Many patients prioritize the ability to return to sports following shoulder replacement surgeries, including total shoulder arthroplasty (TSA), reverse total shoulder arthroplasty (RTSA), and hemiarthroplasty (HA). While activity levels after hip and knee replacements have been well-established in the literature, studies on this topic in the field of shoulder arthroplasty are relatively limited. A review of the literature regarding athletic activity after shoulder arthroplasty was performed using the PubMed database. All studies relevant to shoulder arthroplasty and return to sport were included. The majority of patients returned to their prior level of activity within six months following TSA, RTSA, and shoulder HA. Noncontact, low demand activities are permitted by most surgeons postoperatively and generally have higher return rates than contact sports or high-demand activities. In some series, patients reported an improvement in their ability to participate in sports following the arthroplasty procedure. The rates of return to sports following TSA (75%-100%) are slightly higher than those reported for HA (67%-76%) and RTSA (75%-85%). Patients undergoing TSA, RTSA, and shoulder HA should be counseled that there is a high probability that they will be able to return to their preoperative activity level within six months postoperatively. TSA has been associated with higher rates of return to sports than RTSA and HA, although this may reflect differences in patient population or surgical indication. PMID- 27672565 TI - Management of Ewing sarcoma family of tumors: Current scenario and unmet need. AB - Ewing sarcoma family tumors (ESFT) are heterogeneous, aggressive group of disease with peak incidence in adolescent and young adults. The outcome has been improved dramatically from 10% with surgery and radiotherapy alone to 65%-70% now, in localized disease, with the introduction of chemotherapy. Chemotherapy regimen evolved from single agent to multiagent with effort of many cooperative clinical trials over decades. The usual treatment protocol include introduction of multi agent chemotherapy in neoadjuvant setting to eradicate systemic disease with timely incorporation of surgery and/or radiotherapy as local treatment modality and further adjuvant chemotherapy to prevent recurrence. Risk adapted chemotherapy in neoadjuvant and adjuvant setting along with radiotherapy has been used in many international collaborative trials and has resulted in improved outcome, more so in patients with localized disease. The role of high dose chemotherapy with stem cell rescue is still debatable. The outcome of patients with metastatic disease is dismal with long term outcome ranges from 20%-40% depending on the sites of metastasis and intensity of treatment. There is a huge unmet need to improve outcome further, more so in metastatic setting. Novel therapy targeting the molecular pathways and pathogenesis of ESFT is very much required. Here we have discussed the current standard of management in patients with ESFT, investigational targeted or novel therapies along with future promises. PMID- 27672566 TI - Casting: Pearls and pitfalls learned while caring for children's fractures. AB - Casting is a routine procedure used for fracture care in the pediatric population. The purpose of this review is to provide pearls and pitfalls that our institution has learned from previous literature. When applying the cast, we recommend using cotton padding for the liner and fiberglass or plaster depending on how much swelling is expected. A well-molded cast must be applied in order to prevent further fracture displacement. Cast valving is a valuable technique that allows a decrease in pressure which prevents discomfort and complications like compartment syndrome. Preventing thermal injuries, skin complications, and a wet cast are other important considerations when caring for casts. Appropriate use of a cast saw, avoiding pressure spots, and properly covering the cast are ways to respectively prevent those complications. Lastly, patient education remains one of the most valuable tools in ensuring proper cast maintenance. PMID- 27672567 TI - Implant retention after acute and hematogenous periprosthetic hip and knee infections: Whom, when and how? AB - Periprosthetic joint infections (PJI) of the hip and the knee are grossly classified as early post-operative, acute hematogenous and late chronic infections. Whereas two-stage exchange arthroplasty is the standard of care in North America for treating chronic infections, irrigation and debridement (I and D) with retention of implants has been used in an attempt to treat the other two types of PJIs. The rationale of this approach is that a PJI may be eradicated without the need of explanting the prostheses, as long as it has not transitioned into a chronic state. With the present paper, we review current evidence regarding the role of I and D with implant retention for treating PJIs of the hip and the knee. While a very wide range of success rates is reported in different studies, a short period of time between initiation of symptoms and intervention seems to play a prominent role with regards to a successful outcome. Moreover, pathogens of higher virulence and resistance to antibiotics are associated with a poorer result. Specific comorbidities have been also correlated with a less favorable outcome. Finally, one should proceed with serial I and Ds only under the condition that a predefined, aggressive protocol is applied. In conclusion, when treating a PJI of the hip or the knee, all the above factors should be considered in order to decide whether the patient is likely to benefit from this approach. PMID- 27672568 TI - Surgical treatment of Lenke 5 adolescent idiopathic scoliosis: Comparison of anterior vs posterior approach. AB - AIM: To compare the posterior vs anterior approaches for fusion of Lenke 5 adolescent idiopathic scoliosis curves, matched for curve magnitude and for the distal level of fixation (dLOF) standardized to the third lumbar vertebrae (L3). METHODS: A prospectively collected multicenter database was used for this retrospective comparative study. Our dependent variables included sagittal and coronal radiographic measurements, number of fused vertebrae, estimated blood loss, length of hospitalization and SRS total and individual domain scores at the two-year follow-up. Subject demographics were similar for all group comparisons. Independent t-test was used to compare groups for all analyses at P < 0.01. RESULTS: For all matched cases of Lenke 5 curves, a selective approach was used only 50% of the time in cases undergoing a posterior fusion. When comparing a posterior selective approach to an anterior selective approach, surgeons utilizing a posterior approach fused significantly more levels than surgeons using an anterior approach with no other significant differences in radiographic or SRS outcomes (Ant = 4.8 +/- 1.0 levels vs post = 6.1 +/- 1.0 levels, P < 0.0001). When the dLOF was standardized to L3, the anterior approached provided significantly greater lumbar Cobb percent correction than the posterior approach (Ant = 69.1% +/- 12.6% vs post = 54.6% +/- 16.4%, P = 0.004), with no other significant radiographic or SRS score differences between approaches. CONCLUSION: Surgeons treating Lenke 5c curves with a posterior instrumentation and fusion vs an anterior approach include more motion segments, even with a selective fusion. When controlled for the distal level of fixation, the anterior approach provides greater correction of the thoracolumbar curve. PMID- 27672570 TI - Epidemiology of isolated hand injuries in the United Arab Emirates. AB - AIM: To provide suggestions for hand injury prevention by study the demography and risk factors of casualties suffering from isolated hand injuries. METHODS: All trauma patients with isolated hand injuries who were admitted to Al Ain Hospital for more than 24 h during a period of 3 years were studied. Patient demographics, location, mechanism/time of injury, and length of hospital stay were all analyzed. RESULTS: Two hundred and ten patients were studied. Their mean age was 29.7 years. Males constituted 92%. Sixty-five point one percent of all cases were from the Indian subcontinent. The workplace was the most common location of injury (67.1%), followed by the home (17.1%) and road (6.2%). Machinery caused 36.2% of all injuries, followed by heavy object (20.5%) and fall (11%). Cases injured at home were young (P < 0.0001) with an associated higher incidence of females (P < 0.0001). CONCLUSION: Male workers in Al Ain city are at greater risk of sustaining hand injuries, predominantly from machinery. Safety education, personal protection, and the enforcement of safety standards are essential to the prevention and avoidance of hand injury. PMID- 27672571 TI - Risk assessment instruments for screening bone mineral density in a Mediterranean population. AB - AIM: To evaluate the power of six osteoporosis-screening instruments in women in a Mediterranean country. METHODS: Data concerning several osteoporosis risk factors were prospectively collected from 1000 postmenopausal women aged 42-87 years who underwent dual-energy X-ray absorptiometry (DEXA) screening. Six osteoporosis risk factor screening tools were applied to this sample to evaluate their performance and choose the most appropriate tool for the study population. RESULTS: The most important screening tool for osteoporosis status was the Simple Calculated Osteoporosis Risk Estimation, which had an area under the curve (AUC) of 0.678, a sensitivity of 72%, and a specificity of 72%, with a cut-off point of 20.75. The most important screening tool for osteoporosis risk was the Osteoporosis Self-assessment Tool, which had an AUC of 0.643, a sensitivity of 77%, and a specificity of 46%, with a cut-off point of -2.9. CONCLUSION: Some commonly used clinical risk instruments demonstrate high sensitivity for distinguishing individuals with DEXA-ascertained osteoporosis or reduced bone mineral density. PMID- 27672569 TI - Attitudes and diagnostic practice in low back pain: A qualitative study amongst Greek and British physiotherapists. AB - AIM: To explore current diagnostic practice and attitudes of Greek and United Kingdom physiotherapists (PTs) on assessing low back pain (LBP) patients. METHODS: Three focus groups were undertaken, followed by a structured questionnaire-type survey comprising 23 health professionals and a random stratified sample of 150 PTs, respectively. Twenty-nine themes relating to LBP diagnostic practice emerged. These were then given to 30 British PTs assessing their level of agreement with their Greek counterparts. Analysis was performed by percentage agreements and chi (2) tests. RESULTS: The survey was divided into three subsections; PTs' attitudes on LBP assessment, patients' attitudes and diagnostic/healthcare issues, each constituting 14, 7 and 8 statements, respectively. Over half of the statements fell within the 30%-80% agreement between Greece and United Kingdom whereas, 5 statements reported low (< 10%) and 8 statements demonstrated high (> 90%) PT percentage agreement. Similarities across British and Greek PTs were detected in history taking methods and in the way PTs feel patients perceive physiotherapy practice whereas, re-assessment was undertaken less frequently in Greece. Diagnosis according to 91% of the Greek PTs is considered a "privilege" which is exclusive for doctors in Greece (only 17% British PTs agreed) and is accompanied with a great overuse of medical investigations. Forty percent of Greek PTs (compared to 0% of British) consider themselves as "executers", being unable to interfere with treatment plan, possibly implying lack of autonomy. CONCLUSION: Although similarities on history taking methods and on patients' attitudes were detected across both groups, gross differences were found in re-assessment procedures and diagnostic issues between Greek and British physiotherapists, highlighting differences in service delivery and professional autonomy. PMID- 27672572 TI - Total knee arthroplasty for treatment of post-traumatic arthritis: Systematic review. AB - AIM: To review and report functional outcomes, complications, and survivorship associated with total knee arthroplasty (TKA) in the treatment of post-traumatic arthritis (PTA). METHODS: We conducted a systematic review according to the PRISMA guidelines. We searched PubMed, Cochrane Library, and SCOPUS in December 2015 for English-language clinical research studies, both prospective and retrospective, examining the use of TKA for the treatment of PTA. All relevant articles were accessed in full. The manual search included references of retrieved articles. We extracted data on patients' demographics and clinical outcomes, including preoperative diagnosis and pre- and post-operative functional scores. We summarized the data and reported the results in tables and text. RESULTS: Sixteen studies, four prospective and ten retrospective, examined patients who underwent TKA for PTA due to fractures of the proximal tibia, patella, and/or distal femur. Eleven studies utilized the Knee Society Scores criteria to assess functional outcomes. All studies utilizing these criteria reported an improvement in functional and knee scores of patients following TKA. Further, studies reported an increased range of motion (ROM) and reduction of pain following surgery. The most commonly reported complications with TKA included infection, stiffness, wound complications, intraoperative rupture of tendons, and osteolysis/polyethylene wear. The overwhelming majority of these complications occurred within the first two years following surgery. Six studies examined the survivorship of TKA with subsequent revision for any reason as an endpoint. Compared to patients with osteoarthritis, patients with PTA required more revisions, the majority for polyethylene wear. CONCLUSION: Although associated with higher complication rates, TKA is an effective treatment for PTA, as it improves ROM, pain and functional outcomes. PMID- 27672575 TI - Compartment syndrome following total knee replacement: A case report and literature review. AB - Compartment syndrome is a rare complication of total knee replacement (TKR) surgery that needs prompt diagnosis and treatment as it may be associated with high morbidity and mortality. We have found very few reports in the literature describing compartment syndrome after TKRs and therefore, present a relevant case which occurred in the immediate postoperative phase and was treated with fasciotomy and subsequent operations to close the soft tissue defects. PMID- 27672574 TI - Arterial complications, venous thromboembolism and deep venous thrombosis prophylaxis after anterior cruciate ligament reconstruction: A systematic review. AB - AIM: To summarize the current knowledge on vascular complications and deep venous thrombosis (DVT) prophylaxis after anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. MEDLINE, EMBASE, Cochrane, Web of Science, CINAHL, PubMed publisher, and Google scholar medical literature databases were searched up to November 10, 2015. Any arthroscopic surgical method of primary or revision intra-articular ACL reconstruction of all graft types in humans was included. A risk of bias assessment was determined. RESULTS: Fourty-seven studies were included in the review. Pseudaneurysms were the most frequently reported arterial complication after ACL reconstruction, irrespective of graft type or method of graft fixation with an incidence of 0.3%. The time to diagnosis of arterial complications after ACL reconstruction varied from days to mostly weeks but even years. After ACL reconstruction without thromboprophylaxis, the incidence of DVT was 9.7%, of which 2.1% was symptomatic. The incidence of pulmonary embolism was 0.1%. Tourniquet time > 2 h was related to venous thromboembolism. Thromboprophylaxis is indicated in patients with risk factors for venous thromboembolism. CONCLUSION: After ACL reconstruction, the incidence of arterial complications, symptomatic DVT and pulmonary embolism was 0.3%, 2.1% and 0.1% respectively. Arterial complications may occur with all types of arthroscopic ACL reconstruction, methods of graft fixation as well as any type of graft. Patients considered to be at moderate or high risk of venous thromboembolism should routinely receive thromboprophylaxis after ACL reconstruction. PMID- 27672576 TI - Lateral subtalar dislocation: Case report and review of the literature. AB - A case of complicated lateral subtalar dislocation is presented and the literature concerning this injury is reviewed. Subtalar joint dislocations are rare and often the result of a high-energy trauma. Complications include avascular necrosis of the talus, infection, posttraumatic osteoarthritis requiring arthrodesis and chronic subtalar instability. Negative prognostic factors include lateral and complicated dislocations, total talar extrusions, and associated fractures. A literature search was performed to identify studies describing outcome after lateral subtalar joint dislocation. Eight studies including fifty patients could be included, thirty out of 50 patients suffered a complicated injury. Mean follow-up was fifty-five months. Ankle function was reported as good in all patients with closed lateral subtalar dislocation. Thirteen out of thirty patients with complicated lateral subtalar joint dislocation developed a complication. Avascular necrosis was present in nine patients with complicated injury. Four patients with complicated lateral subtalar dislocation suffered deep infection requiring treatment with antibiotics. In case of uncomplicated lateral subtalar joint dislocation, excellent functional outcome after closed reduction and immobilization can be expected. In case of complicated lateral subtalar joint dislocation immediate reduction, wound debridement and if necessary (external) stabilisation are critical. Up to fifty percent of patients suffering complicated injury are at risk of developing complications such as avascular talar necrosis and infection. PMID- 27672573 TI - Biologic agents for anterior cruciate ligament healing: A systematic review. AB - AIM: To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing. METHODS: A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing. RESULTS: The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series. CONCLUSION: There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement. PMID- 27672577 TI - Retained Wireless Capsule Endoscope in a Girl with suspected Crohn's Disease. AB - Wireless capsule endoscopy (WCE) is one of the great milestones in the field of gastroenterology. It is versatile in image acquisition, painless and can reach parts of the small bowel not amenable to conventional endoscopy. The commonest complication with WCE is retention of the capsule. We report a case of retained capsule in a child who was being investigated for obscure gastrointestinal bleeding (OGIB). Operative intervention was required for its retrieval after two weeks of expectant management. PMID- 27672578 TI - Inflammatory Myofibroblastic Tumor of Common Bile Duct in a Girl. AB - Inflammatory myofibroblastic tumor (IMT) is a rare, low grade malignant lesion which can occur anywhere in the body. In children it is usually found in the visceral soft tissues with a potential for local invasion and recurrence, and rarely distant metastasis. We report the diagnostic dilemma faced in the management of a 12-year old girl who presented with obstructive jaundice with a mass lesion at the distal end of the common bile duct. She underwent a tumor resection with a bilio-enteric bypass followed by a course of oral steroids and celecoxib. PMID- 27672579 TI - Disc Battery - An Unusual Vaginal Foreign Body in a Child. AB - Disc battery ingestion and esophageal injury is well-known in children. Insertion of a disc/lithium battery into body's natural orifices is rarely reported. We present a case of self-insertion of a lithium battery into the vagina by a 2 1/2 year old female. Vaginoscopy was performed and the battery was retrieved which had corroded and caused vaginal ulceration. Post-operative outcome was favorable. Treating physicians must be aware of the hazardous effects of insertion of lithium batteries as it may cause significant damage in a short period. PMID- 27672580 TI - Right Parotid Fibrolipoma: A Rare Lesion in a Child. AB - Lipoma rarely involves parotid gland especially in children. An 11-year-old boy presented with right parotid swelling. Preoperative workup including CT scan and FNAC gave suspicion of parotid gland lipoma. The diagnosis was confirmed on histopathology after complete excision of the mass. PMID- 27672581 TI - Symptomatic Mullerian Duct Cyst in a Male Infant. AB - Symptomatic Mullerian duct cyst is a rare entity in children. A 9-month-old male infant presented with bowel and urinary obstructive symptoms. Imaging investigations revealed a cystic mass in the rectovesical pouch compressing bladder neck and rectum. At laparotomy, a Mullerian duct cyst was found. Most of the cyst was excised and the remaining cyst mucosa was cauterized. The child improved thereafter. PMID- 27672582 TI - Neurenteric Cyst Presenting with Bleeding Per Rectum. AB - Neurenteric cyst in the thoracic cavity may produce a myriad of clinical features. We report a 7-month-old girl who presented with significant bleeding per rectum. On imaging, a mediastinal cystic structure with air-fluid levels was evident with cervico-thoracic vertebral anomalies. The cyst was excised and histopathology showed intestinal mucosal lining with heterotopic pancreatic tissue confirming the diagnosis of neurenteric cyst. PMID- 27672583 TI - Malrotation and Midgut Volvulus associated with Asymptomatic Duplication Cyst of Jejunum. AB - Gastrointestinal duplications can affect any part of the alimentary tract and are notorious for their variable presentation. Their association with malrotation and midgut volvulus is rare. We describe an 8-year old boy presented with episodes of abdominal pain. Radiological workup showed whirlpool sign and abnormal relationship of mesenteric vessels. At operation, malrotation with chronic volvulus was found. Incidentally, a jejunal communicating duplication cyst was also noted. PMID- 27672584 TI - Tetra-Amelia Syndrome. PMID- 27672585 TI - The role of LOX-1 on innate immunity against Aspergillus keratitis in mice. AB - AIM: To explore the effects of lectin-like ox-LDL receptor (LOX-1) on innate immunity against Aspergillus fumigatus (A. fumigatus ) in mice cornea. METHODS: The mRNA levels of LOX-1 were tested in normal and A. fumigatus infected corneas of C57BL/6 and BALB/c mice. The expression of LOX-1, pro-inflammatory cytokines TNF-alpha, CXCL1 and IL-6, anti-inflammatory cytokines IL-10, and matrix metalloproteinase 9 (MMP9) were tested with treatment with LOX-1 neutralizing antibody or control IgG in A. fumigatus infected corneas of C57BL/6. Macrophages and neutrophils were extracted from susceptible C57BL/6 mice, and pretreated with LOX-1 neutralizing antibody or IgG, then stimulated with A. fumigatus. The mRNA levels of LOX-1, TNF-alpha, CXCL1, IL-6, IL-10 and MMP9 were evaluated by polymerase chain reaction. RESULTS: The expression of LOX-1 was significantly increased in C57BL/6 mice corneas after A. fumigatus infection compared with BABL/c mice. After treatment with LOX-1 neutralizing antibody, the expression of LOX-1, TNF-alpha, CXCL1, IL-6, MMP9 and IL-10 in C57BL/6 corneas were significantly decreased compared with treatment with control IgG; the expression of LOX-1, CXCL1, IL-6 and IL-10 were significantly decreased in macrophages, while TNF-alpha and MMP9 expressions had no change; LOX-1, TNF-alpha, CXCL1, IL 6, MMP9 and IL-10 expressions were significantly decreased in neutrophils. CONCLUSION: The expression of LOX-1 can affect the expression of pro-inflammatory and anti-inflammatory cytokines in fungal infected corneas, macrophages and neutrophils of C57BL/6. LOX-1 inhibition rebalances the inflammatory response of fungal keratitis in mice. PMID- 27672586 TI - Inhibiting the effect of (90)Sr-(90)Y ophthalmic applicators on rat corneal neovascularization induced by sutures. AB - AIM: To investigate a practical technique used to inhibit corneal angiogenesis with a (90)Sr-(90)Y ophthalmic applicator. METHODS: A (90)Sr-(90)Y ophthalmic applicator was detected with a radioactive nuclide application treatment healthy protection standard. The applicator used was produced through medical dosimetry research; it had a concave applicator add measured the applicator temperature, serviceable humidity range, applicator appearance status, applicator radiation homogeneity, radioautography, and radiological safety of the original applicator surface. A vessel model was established using newborn rats, with sutures around the corneal limbus. Corneal neovascularization (CNV) were observed with a slit lamp. The new vessel length and response area were measured. RESULTS: Low-dose radiation can inhibit CNV after corneal sutures. The absorbed dose of the applicator (0.046 Gy/s) was safe for the treatment of it. The lengths of new vessels and the areas of new vessels were lower than the new born vessel rat group (P<0.01). CONCLUSION: The optimal radiation dose emitting from the applicator can be safe and potentially used in humans. PMID- 27672587 TI - Attenuation of corneal neovascularization by topical low-molecular-weight heparin taurocholate 7 without bleeding complication. AB - AIM: To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparin-taurocholate 7 (LHT7) on corneal neovascularization (CoNV). METHODS: Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each. The central corneas were cauterized using a silver/potassium nitrate solution. From 2d after cauterization, 12.5 mg/mL (low LHT7 group) or 25 mg/mL (high LHT7 group) LHT7 was topically administered three times daily; 12.5 mg/mL bevacizumab was topically administered as positive control (bevacizumab) group, with normal saline (NS) administered as negative control (NS group). The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk. RESULTS: The 4 study groups did not have different CoNV percentages at 1wk after injury (P>0.05). However, the low LHT, high LHT, and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk (all P<0.05). No significant differences in CoNV percentage were found among the low LHT, high LHT, and bevacizumab groups (all P>0.05). All groups except the NS group had lower CoNV percentages at 2wk post-injury than the levels observed at 1wk (all P<0.05). CONCLUSION: Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat. PMID- 27672588 TI - Comprehensive analysis of genetic variations in strictly-defined Leber congenital amaurosis with whole-exome sequencing in Chinese. AB - AIM: To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis (LCA) in Chinese. METHODS: LCA subjects and their families were retrospectively collected from 2013 to 2015. Firstly, whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found, and then homozygous sites was selected, candidate sites were annotated, and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant (SIFT), Polyphen-2, Mutation assessor, Condel, and Functional Analysis through Hidden Markov Models (FATHMM). Furthermore, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test. Sanger sequencing was used to validate single-nucleotide variations (SNVs). Expanded verification was performed in the rest patients. RESULTS: Totally 51 LCA families with 53 patients and 24 family members were recruited. A total of 104 SNVs (66 LCA-related genes and 15 co-segregated genes) were submitted for expand verification. The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families. Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion, biological adhesion, retinoid metabolic process, and eye development biological adhesion. Additionally, WFS1 and STAU2 had the highest homozygous frequencies. CONCLUSION: LCA is a highly heterogeneous disease. Mutations in KRT12, CYP1A1, WFS1, and STAU2 may be involved in the development of LCA. PMID- 27672589 TI - A novel model of retinopathy of prematurity in normobaric hyperoxic conditions. AB - AIM: To examine changes in retinal vasculature after treatment with different oxygen concentrations from common retinopathy of prematurity (ROP) models and to determine a novel and practical ROP model. METHODS: A sample of 14 newborn Sprague-Dawley rats was used. The study group (n=7) was exposed to 95% oxygen for 4h per day followed by normoxic laboratory conditions for 20h. This cycle was repeated for 14d. The control group (n=7) was subjected to normobaric normoxic conditions. On postnatal day 14 (P14), the two groups were placed in room air for 7d. On P21, the two groups were examined using indirect ophthalmoscopy. All eyes were enucleated for immunofluorescence (IF) staining of the vasculature of retinas and analysis of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1alpha), placental growth factor (PLGF) in vitreous humor, and then the rats were sacrificed by decapitation. All procedures were repeated using another litter of 14 pups. RESULTS: In the study group and under normobaric hyperoxic conditions, retinal neovascularization and peripheral avascular retina were determined in 85% of the rats through indirect ophthalmoscopic examination. Also IF staining of retina of the study group showed retarded peripheral vascular growth. The difference between the two groups for VEGF, HIF-1alpha and PLGF concentrations of vitreous humor was statistically significant (P=0.003, 0.007, 0.027 respectively). CONCLUSION: Fluctuating oxygen concentrations are primarily responsible for retinal neovascularization. Our new ROP model is practical and applicable for all retinal neovascularization studies, considering the laboratory procedures. PMID- 27672590 TI - Construction of adenovirus vectors encoding the lumican gene by gateway recombinant cloning technology. AB - AIM: To construct adenovirus vectors of lumican gene by gateway recombinant cloning technology to further understand the role of lumican gene in myopia. METHODS: Gateway recombinant cloning technology was used to construct adenovirus vectors. The wild-type (wt) and mutant (mut) forms of the lumican gene were synthesized and amplified by polymerase chain reaction (PCR). The lumican cDNA fragments were purified and ligated into the adenovirus shuttle vector pDown multiple cloning site (MCS)-/internal ribozyme entry site (IRES)/enhanced green fluorescent protein (EGFP). Then the desired DNA fragments were integrated into the destination vector pAV.Des1d yielding the final expression constructs pAV.Ex1d-cytomegalovirus (CMV)>wt-lumican/IRES/EGFP and pAV.Ex1d-CMV>mut lumican/IRES /EGFP, respectively. RESULTS: The adenovirus plasmids pAV.Ex1d CMV>wt-lumican/IRES/EGFP and pAV.Ex1d-CMV>mut-lumican/IRES/EGFP were successfully constructed by gateway recombinant cloning technology. Positive clones identified by PCR and sequencing were selected and packaged into recombinant adenovirus in HEK293 cells. CONCLUSION: We construct adenovirus vectors containing the lumican gene by gateway recombinant cloning technology, which provides a basis for investigating the role of lumican gene in the pathogenesis of high myopia. PMID- 27672591 TI - Effects of posterior corneal astigmatism on the accuracy of AcrySof toric intraocular lens astigmatism correction. AB - AIM: To evaluate the effects of posterior corneal surface measurements on the accuracy of total estimated corneal astigmatism. METHODS: Fifty-seven patients with toric intraocular lens (IOL) implantation and posterior corneal astigmatism exceeding 0.5 diopter were enrolled in this retrospective study. The keratometric astigmatism (KA) and total corneal astigmatism (TA) were measured using a Pentacam rotating Scheimpflug camera to assess the outcomes of AcrySof IOL implantation. Toric IOLs were evaluated in 26 eyes using KA measurements and in 31 eyes using TA measurements. Preoperative corneal astigmatism and postoperative refractive astigmatism were recorded for statistical analysis. The cylindrical power of toric IOLs was estimated in all eyes. RESULTS: In all cases, the difference of toric IOL astigmatism magnitude between KA and TA measurements for the estimation of preoperative corneal astigmatism was statistically significant. Of a total of 57 cases, the 50.88% decreased from Tn to Tn-1, and 10.53% decreased from Tn to Tn-2. In all cases, 5.26% increased from Tn to Tn+1. The mean postoperative astigmatism within the TA group was significantly lower than that in the KA group. CONCLUSION: The accuracy of total corneal astigmatism calculations and the efficacy of toric IOL correction can be enhanced by measuring both the anterior and posterior corneal surfaces using a Pentacam rotating Scheimpflug camera. PMID- 27672593 TI - Toric markers-assisted implantation of the scleral-fixated intraocular lens. AB - AIM: To evaluate the efficacy of toric intraocular lens markers-assisted implantation of the scleral-fixated intraocular lens (SFIOL). METHODS: From October 2010 to December 2013, all patients who had undergone secondary SFIOL implantation were assigned to group 1 and 2, in group 1 SFIOL was performed with the assist of radial keratotomy (RK)-marker, and in group 2 SFIOL was performed with the assisted of toric intraocular lens markers (T-and axis markers). Patients' demographic data and information on baseline preoperative visual acuity, indication for surgery and latest postoperative visual acuity were collected and analyzed. The haptic and optic positions were determined by ultrasound biomicroscopy. The optic tilt angle and decentration distance were measured. RESULTS: The study evaluated 43 eyes of 43 patients ranging in age from 3 to 66y. Group 1 comprised 24 eyes (24 patients) and group 2, 19 eyes (19 patients). Uncorrected reoperative acuity was improved on all the eyes postoperatively. The improved postoperative acuity was significantly more in group 2 than that in group 1 (1.11+/-0.38 vs 0.82+/-0.45 logMAR; F=4.85, P=0.03). Ultrasonic biomicrograph examination showed that the rate of haptic asymmetry was significantly higher in group 1 (42%, 10/24) than that in group 2 (11%; 2/19) (Chi square=3.68, P=0.04). The mean tilted degree in group 1 was significantly higher than that in group 2 (P=0.04). Mean decentration distance in group 1 was greater than that in group 2 (P=0.03). CONCLUSION: During SFIOL the toric markers help the surgeon identify the placement of fixation more precisely than that with the use of RK marker. PMID- 27672592 TI - Evaluation of anterior and posterior surfaces of the cornea using a dual Scheimpflug analyzer in keratoconus patients implanted with intrastromal corneal ring segments. AB - AIM: To evaluate corneal parameters measured with a dual Scheimpflug analyzer in keratoconus patients implanted with intrastromal corneal ring segments (ICRS). METHODS: Fifty eyes of 40 keratoconus patients had Ferrara ICRS implantation from November 2010 to April 2014. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction, keratometry, asphericity, elevation, pachymetry, root mean square (RMS), spherical aberration and coma were studied. All patients were evaluated using a dual Scheimpflug system. RESULTS: The mean follow-up time after the procedure was 12.7mo. The mean UCVA improved from 0.82 to 0.31 (P<0.001); the mean BCVA improved from 0.42 to 0.05 (P<0.0001), the mean spherical refraction changed from -3.06+/-3.80 D to -0.80+/-2.5 D (P<0.0001) and the mean refraction astigmatism reduced from -4.51+/-2.08 D to -2.26+/-1.18 D (P<0.0001). The changes from preoperative to postoperative, in parameters of the anterior and posterior surface of the cornea, were statistically significant except the elevation posterior at the apex of the cornea and posterior asphericity. CONCLUSION: The implantation of Ferrara ICRS induces changes in both anterior and posterior surfaces of the cornea. PMID- 27672594 TI - A modified approach to actively remove high viscosity silicone oil through 23 gauge cannula. AB - AIM: To report a simple approach to actively remove high viscosity silicone oil through a 23-gauge cannula via pars plana. METHODS: Forty-eight eyes of 48 patients underwent silicone oil (5700 centistokes) removal (SOR) were enrolled. A section of blood transfusion set was prepared to connect a standard 23-gauge cannula and vitrectomy machine. Silicone oil was removed with suction of 500-mm Hg vacuum through the cannula. Main outcome measures were SOR duration, number of sutured sites, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications. RESULTS: Silicone oil was successfully removed in all cases. The mean SOR time was 5.70+/-0.85min. Nine eyes (18.75%) needed suture partial sclerotomies. No intraoperative complications were noted. Transient hypotony (<=8 mm Hg) was seen in 3 eyes (6.25%) on postoperative day 1, but all resolved within 1wk. Retinal reattachment was achieved in all cases and no other postoperative complications were noted during 3-month following-up. BCVA at the final visit improved or stabilized in all patients comparing to the preoperative level. CONCLUSION: Active removal of high viscosity silicone oil through a 23-gauge instrument cannula jointed with blood transfusion set is a practical and reliable technique when considering two sides of efficacy and safety. PMID- 27672595 TI - Ultra-wide field imaging system and traditional retinal examinations for screening fundus changes after cataract surgery. AB - AIM: To compare the results of non-mydriatic ultra-wide field imaging system, mydriatic slit-lamp lens (Volk +90 D) and mydriatic Goldmann three-mirror contact lens examinations in screening fundus lesions among patients after cataract surgery. METHODS: Non-mydriatic images were obtained with an Optomap panoramic 200Tx (Optomap 200Tx) 3d after surgery and graded by a blinded ophthalmologist. A mydriatic slit-lamp lens examination was performed by another blinded retinal specialist on the same day. A third blinded retinal specialist examined patients two weeks after surgery using a Goldmann three-mirror contact lens. RESULTS: In total, 160 patients (184 eyes) were examined, and 66, 69, and 75 cases of retinal lesion(s) were identified using the Optomap 200Tx, slit-lamp lens, and Goldmann three-mirror contact lens, respectively. In 13 cases, fundus changes were sight threatening. The results obtained by Optomap 200Tx examination and by mydriatic slit-lamp lens examination have good consistency (P=0.375, Kappa=0.942). The mydriatic Goldmann three-mirror lens examination revealed more fundus lesions but are consistent with Optomap 200Tx (P=0.004, Kappa=0.897) and mydriatic slit-lamp lens examination (P=0.031, Kappa=0.932). CONCLUSION: Early post-operative fundus screening in cataract patients is extremely important and necessary to prevent further vision loss. Wide-field imaging is a feasible and convenient tool for fundus examination that can be used as a primary screening method among patients after cataract surgery. PMID- 27672596 TI - Influence of CFH, HTRA1 and ARMS2 polymorphisms in the response to intravitreal ranibizumab treatment for wet age-related macular degeneration in a Spanish population. AB - AIM: To determine whether gene polymorphisms of the major genetic risk loci for age-related macular degeneration (AMD): ARMS2 (rs10490923), the complement factor H (CFH) (rs1410996) and HTRA1 (rs11200638) influence the response to a treatment regimen with ranibizumab for exudative AMD. METHODS: This study included 100 patients (100 eyes) with exudative AMD. Patients underwent a treatment with ranibizumab injections monthly during three months. Reinjections were made when the best corrected visual acuity (BCVA) decrease five letters (ETDRS) or central subfield retinal thickness gained 100 um in optical coherence tomography image. Genotypes (rs10490923, rs1410996 and rs11200638) were analyzed using TaqMan probes or polymerase chain reaction-restricted fragment length polymorphisms analysis. RESULTS: There were no statistically significant differences in allelic distribution of CFH (rs1410996), ARMS2 (rs10490923) and HTRA1 (rs11200638) polymorphisms regarding to response to ranibizumab treatment. CONCLUSION: Ranibizumab treatment response is not related to CFH (rs1410996), ARMS2 (rs10490923) and HTRA1 (rs11200638) poymorphisms. PMID- 27672597 TI - Comparison of scleral buckling using wide-angle viewing systems and indirect ophthalmoscope for rhegmatogenous retinal detachment. AB - AIM: To compare the effects of scleral buckling using wide-angle viewing systems (WAVS) with that using indirect ophthalmoscope for the treatment of rhegmatogenous retinal detachment. METHODS: The study was a retrospective analyses of the medical records of 94 eyes (94 patients) with rhegmatogenous retinal detachment. Among them, 47 eyes underwent scleral buckling using WAVS with endoilluminator (Group W), and 47 eyes underwent scleral buckling using indirect ophthalmoscope (Group I). Surgical durations, primary success rate, best corrected visual acuities (BCVA), delayed subretinal fluid absorptions and surgical complications were compared between the two groups. RESULTS: At baseline, there were no statistical differences between the two groups in patient's age (P=0.997), gender (P=0.853), symptom duration (P=0.216), BCVA (P=0.389), refractive error (P=0.167), intraocular pressure (P=0.595), the number of retinal breaks (P=0.832), the extent of retinal detachment (P=0.246), subretinal demarcation line (P=0.801), and macular detachment (P=0.811). The follow-up period was 12mo. The surgical durations in Group W (with or without encircling buckling) were significant shorter than those in Group I (P<0.001 respectively). The primary success rate was 94.27% in Group W, which was similar to that in Group I (92.38%, P = 0.931). The BCVA in Group W was better than that in Group I (P<0.001) at 1-month follow-up visit. However, there were no significant differences between the two groups at 3-month (P=0.221), 6-month (P=0.674), and 12-month (P=0.363) follow-up visits respectively. Delayed subretinal fluid absorptions were more common in Group I than in Group W at 1 month (P=0.045) follow-up visit, but there were no significant differences between the two groups at 3-month (P=0.111), 6-month (P=1.000) and 12-month follow-up visits respectively. CONCLUSION: Scleral buckling using WAVS can be an alternative choose for rhegmatogenous retinal detachment. PMID- 27672598 TI - Analyses on the misdiagnoses of 25 patients with unilateral optic nerve sheath meningioma. AB - AIM: To investigate clinical features of optic nerve sheath meningioma (ONSM) that was misdiagnosed, and to find methods to reduce the misdiagnoses. METHODS: Retrospective series study. Twenty-five misdisgnosed patients with unilateral ONSM were collected from Jan. 2008 to Jan. 2015 and the clinical records reviewed. RESULTS: Patients were misdiagnosed with acute papillitis most frequently (n=17), immediately followed by optic atrophy (n=8), ischemic optic neuropathy (n=5), acute retrobulbar optic neuritis (n=5), optic disc vasculitis (n=3). For each patient, the minimum frequency of misdiagnoses was once and the maximum was 4 times. As for the lasting time of being misdiagnosed, the shortest was 1.5mo and the longest was 45mo. Twenty-one cases (84%) were once treated with glucocorticoids, and its side effects was found in seventeen patients. Twenty patients (80%) complained with varying degree of vision loss. When a definite diagnosis was made, sixteen cases (64%) showed slight exophthalmos and eighteen cases (72%) had the tubular ONSM. CONCLUSION: ONSM without loss obvious exophthalmos is easily misdiagnosed in clinic, and for most of these ONSMs are tubular. PMID- 27672599 TI - Effects of upper lid blepharoplasty on visual quality in patients with lash ptosis and dermatochalasis. AB - AIM: To assess the effects of upper lid blepharoplasty on visual quality. METHODS: Seventy-three eyelids of 39 patients were subjected to upper lid blepharoplasty. Pre- and post-operative contrast sensitivity, visual acuity, vertical palpebral aperture and the degree of lash ptosis were measured. RESULTS: The mean log contrast sensitivities under photopic (P=0.017) and scotopic conditions (P=0.009) were improved after surgery, and these differences were significant. The degree of lash ptosis was also decreased after blepharoplasty (P<0.001). CONCLUSION: In our study, a significant increase in contrast sensitivity was found after surgery. These results suggest that upper lid blepharoplasty can be helpful for improving visual quality. PMID- 27672600 TI - Retinal vessels caliber changes after strabismus surgery: results of 6mo follow up. AB - AIM: To evaluate the effect of strabismus surgery on retinal vessels calibers with digital color fundus photographs. METHODS: Two hundred consecutive strabismus patients underwent surgery, and 118 patients (female/male, 55/63) who finished 6-month follow-up were finally included in this study. Optic disc centered digital color fundus photographs of both eyes of all patients were taken prior to surgery and 6mo post surgery. The retinal vascular caliber of 116 operated eyes were measured using the computer program IVAN. The operated eyes were divided into 3 groups according to the surgical methods, recession of one muscle, one muscle recession and one muscle folding, one muscle resection and one muscle recession. The effect of number of altered muscles on retinal vessels was analyzed using statistic software SPSS 16.0. RESULTS: The mean age was 12.4+/ 8.6y. Averaged central retinal artery equivalent (CRAE) of all patients was 120.31+/-23.02 um preoperatively, and 122.87+/-15.93 um six months after surgery. Averaged central retinal vein equivalent (CRVE) was 171.11+/-31.73 um preoperatively and 175.02+/-21.00 um postoperatively. There was no significant difference of averaged CRAE (P=0.22) or CRVE (P=0.19) before and after operation. Averaged arteriole to venule ratio (AVR) was 0.71+/-0.07 before surgery and 0.70+/-0.07 after surgery. Comparison of preoperative and postoperative retinal vessels calibers among different surgical groups did not show significant differences. Also, there was no advantage of rectus muscle folding to muscle resection. CONCLUSION: Up to 6mo after strabismus surgery, the retinal vascular calibers were not altered. No more than two muscles in one surgery are safe for retinal perfusion. PMID- 27672601 TI - Scientometric analysis and mapping of 20 years of glaucoma research. AB - AIM: To provide a scientometric analysis in the field of glaucoma. METHODS: A bibliometric method was used to obtain a view of the scientific production in field of glaucoma by data extracted from the Institute for Scientific Information (ISI) from 1993 to 2013. Specific parameters were retrieved from the ISI. Articles about glaucoma were analyzed regarding the topics' structure, history, and document relationships using HistCite software. Also, the trends in the most influential publications and authors were analyzed. RESULTS: The number of articles was constantly increasing, and most highly cited articles addressed clinical and epidemiologic topics in this field. During the past three years, there has been a trend towards genomic research studies and also more molecular translational research. CONCLUSION: This was the first scientometric report on glaucoma, analyzing the characteristics of papers and the trends in scientific production. A constant increase was observed in the number of papers, while the subject of papers had a shift in the past three years towards genomic research studies. PMID- 27672602 TI - Public's knowledge of the differences between ophthalmologists and optometrists: a critical issue in eye care service utilisation. AB - AIM: To assess the public's knowledge of the differences between ophthalmologists and optometrists and identify the factors associated with knowledge. METHODS: The study was a population-based random survey of adults aged 18 years or older conducted in Enugu, south eastern Nigeria, between March and June, 2011. Data on respondents' socio-demographics, clinical profile, and knowledge of the differences between ophthalmologists and optometrists were collected using a 28 item questionnaire. Data were analysed using descriptive and analytical statistics. Values of P<0.05 were considered statistically significant. RESULTS: The respondents (n=394) comprised 198 males and 196 females (sex ratio=1.01:1), aged 18-70 (30.9+/-10.8) years. The majority of respondents were single (57.4%), possessed secondary education (96.9%), employed (65.2%) and had no health insurance (77.4%). Their clinical profile showed previous eye exam 54.1%, spectacle wear 41.6% and contact lens wear 5.6%. In the multivariate analysis, participants' good knowledge of the differences between ophthalmologists and optometrists was significantly associated with educational status (OR: 0.32, 95% CI: 0.23-0.44, P<0.0001, beta=-0.988), employment status (OR: 1.8, 95% CI: 1.45 2.25, P<0.0001, beta=0.124) and previous eye examination (OR: 1.63, 95% CI: 1.29 2.07, P<0.0001, beta=0.549). CONCLUSION: Participants' socio-demographic and clinical characteristics are important predictors of good knowledge. The findings may have implications for all stakeholders in eye care delivery. There is need for knowledge enhancement, by the government and eye care providers, through population-based eye health literacy campaigns. PMID- 27672604 TI - Analysis of optic disc damage by optical coherence tomography in terms of therapy in non-arteritic anterior ischemic optic neuropathy. AB - This study aimed to assess the relationship between the rate of nerve fiber loss in non-arteritic anterior ischemic optic neuropathy (NAION) and time delay before therapy. Total 24 patients received the same treatment within or after 2wk (early and late groups). There were significantly lower level of destruction of nerve fibers (P=0.0014) and significantly better visual field sensitivity (P=0.039) in early group. The results indicate that therapy should be started within 2wk. The degree of ischemic damage due to NAION correlates well with retinal nerve fiber layer thickness and the ischemia-induced decrease in visual field sensitivity. PMID- 27672603 TI - The role of Toll-like receptors in retinal ischemic diseases. AB - Toll-like receptors (TLRs) are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands. Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases, including ischemia reperfusion injury, glaucoma, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). TLRs can be expressed in multiple cells in the retina, such as glial cells, retinal pigment epithelium (RPE), as well as photoreceptor cells and endothelium cells. Activation of TLRs in retina could initiate a complex signal transduction cascade, induce the production of inflammatory cytokines and regulate the level of co-stimulatory molecules, which play prominent roles in the pathogenesis of retinal ischemic diseases. In this review, we summarized current studies about the relationship between TLRs and ischemic retinopathy. A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions. PMID- 27672605 TI - A statistical approach to classification of keratoconus. PMID- 27672606 TI - Urrets-Zavalia syndrome in different methods of keratoplasty. PMID- 27672607 TI - A delayed diagnosis of unsuspected retinoblastoma in an in vitro fertilisation infant with retinopathy of prematurity. PMID- 27672608 TI - Macular hole closure following anti-vascular endothelial growth factor injection in an eye with myopic choroidal neovascularization. PMID- 27672609 TI - A novel nonsense mutation of GPR143 gene in a Korean kindred with X-linked congenital nystagmus. PMID- 27672610 TI - Jaw lesions associated with impacted tooth: A radiographic diagnostic guide. AB - This review article aimed to introduce a category of jaw lesions associated with impacted tooth. General search engines and specialized databases such as Google Scholar, PubMed, PubMed Central, MedLine Plus, Science Direct, Scopus, and well recognized textbooks were used to find relevant studies using keywords such as "jaw lesion", "jaw disease", "impacted tooth", and "unerupted tooth". More than 250 articles were found, of which approximately 80 were broadly relevant to the topic. We ultimately included 47 articles that were closely related to the topic of interest. When the relevant data were compiled, the following 10 lesions were identified as having a relationship with impacted tooth: dentigerous cysts, calcifying odontogenic cysts, unicystic (mural) ameloblastomas, ameloblastomas, ameloblastic fibromas, adenomatoid odontogenic tumors, keratocystic odontogenic tumors, calcifying epithelial odontogenic tumors, ameloblastic fibro-odontomas, and odontomas. When clinicians encounter a lesion associated with an impacted tooth, they should first consider these entities in the differential diagnosis. This will help dental practitioners make more accurate diagnoses and develop better treatment plans based on patients' radiographs. PMID- 27672611 TI - Panoramic radiographs underestimate extensions of the anterior loop and mandibular incisive canal. AB - PURPOSE: The purpose of this study was to detect the anterior loop of the mental nerve and the mandibular incisive canal in panoramic radiographs (PAN) and cone beam computed tomography (CBCT) images, as well as to determine the anterior/mesial extension of these structures in panoramic and cross-sectional reconstructions using PAN and CBCT images. MATERIALS AND METHODS: Images (both PAN and CBCT) from 90 patients were evaluated by 2 independent observers. Detection of the anterior loop and the incisive canal were compared between PAN and CBCT. The anterior/mesial extension of these structures was compared between PAN and both cross-sectional and panoramic CBCT reconstructions. RESULTS: In CBCT, the anterior loop and the incisive canal were observed in 7.7% and 24.4% of the hemimandibles, respectively. In PAN, the anterior loop and the incisive canal were detected in 15% and 5.5% of cases, respectively. PAN presented more difficulties in the visualization of structures. The anterior/mesial extensions ranged from 0.0 mm to 19.0 mm on CBCT. PAN underestimated the measurements by approximately 2.0 mm. CONCLUSION: CBCT appears to be a more reliable imaging modality than PAN for preoperative workups of the anterior mandible. Individual variations in the anterior/mesial extensions of the anterior loop of the mental nerve and the mandibular incisive canal mean that is not prudent to rely on a general safe zone for implant placement or bone surgery in the interforaminal region. PMID- 27672612 TI - The role of oral physicians in predicting the risk of obstructive sleep apnea: A case-control study. AB - PURPOSE: Obstructive sleep apnea (OSA) is a common medical disorder with serious complications if untreated. Dentists play a vital role in the early diagnosis of this condition, thereby improving patients' prognoses. The purpose of this study was to identify patients with a high risk of OSA using simple cephalometric measurements in patients receiving routine dental care. MATERIALS AND METHODS: The present study was conducted on 206 patients divided into a high-risk group and a control group after answering the Berlin questionnaire. Cephalometric analysis of a digital cephalogram was performed to measure the upper airway diameter (UAD) and mandibular-to-hyoid bone distance (MP-H) by 2 observers at 2 different times. RESULTS: Among 206 patients, 93 (45%) were included in the high risk group and 113 (55%) were in the control group. No significant difference was present between the groups with regard to gender, and the patients ranged in age from 18 to 65 years. The UAD measurements in the high-risk group were significantly lower than in the control group, and the MP-H measurements were significantly higher in the high-risk group than in the control group. The UAD was lower in middle-aged patients in both groups. CONCLUSION: Our study found that the UAD was lower in individuals with a high risk of OSA. Also, we found that middle-aged individuals of both genders were more likely to develop OSA. Dentists play a vital role in diagnosing patients at a high risk for OSA via thorough clinical examinations, risk factor analyses, and simple cephalometric analyses. PMID- 27672613 TI - The effectiveness of optical coherence tomography for evaluating peri-implant tissue: A pilot study. AB - PURPOSE: Optical coherence tomography (OCT) has been investigated as a novel diagnostic imaging tool. The utilisation of this equipment has been evaluated through several studies in the field of dentistry. The aim of this preliminary study was to determine through basic experiments the effectiveness of OCT in implant dentistry. MATERIALS AND METHODS: To assess detection ability, we captured OCT images of implants in each of the following situations: (1) implants covered with mucosae of various thicknesses that were harvested from the mandibles of pigs; (2) implants installed in the mandibles of pigs; and (3) implants with abutments and crowns fixed with temporary cement. The OCT images were captured before cementation, after cementation, and after removing the excess submucosal cement. RESULTS: If the thickness of the mucosa covering the implant body was less than 1 mm, the images of the implants were clearly detected by OCT. In the implants were installed in pigs' mandibles, it was difficult to capture clear images of the implant and alveolar bone in most of the samples. Remnants of excess cement around the implants were visible in most samples that had a mucosa thickness of less than 3 mm. CONCLUSION: Currently, OCT imaging of implants is limited. Cement remnants at the submucosal area can be detected in some cases, which can be helpful in preventing peri-implant diseases. Still, though there are some restrictions to its application, OCT could have potential as an effective diagnostic instrument in the field of implant dentistry as well. PMID- 27672614 TI - The use of digital periapical radiographs to study the prevalence of alveolar domes. AB - PURPOSE: In the present study, we coined the term 'alveolar dome' and aimed to demonstrate the prevalence of alveolar domes through digital periapical radiographs. MATERIALS AND METHODS: This study examined 800 digital periapical radiographs in regard to the presence of alveolar domes. The periapical radiographs were acquired by a digital system using a photostimulable phosphor (PSP) plate. The chi(2) test, with a significance level of 5%, was used to compare the prevalence of alveolar domes in the maxillary posterior teeth and, considering the same teeth, to verify the difference in the prevalence of dome shaped phenomena between the roots. RESULTS: The prevalence of alveolar domes present in the first pre-molars was statistically lower as compared to the other maxillary posterior teeth (p<0.05). No statistically significant difference was observed in the prevalence of alveolar domes between the maxillary first and second molars. Considering the maxillary first and second molars, it was observed that the palatal root presented a lower prevalence of alveolar domes when compared to the distobuccal and mesiobuccal roots (p<0.05). CONCLUSION: The present study coined the term 'alveolar dome', referring to the anatomical projection of the root into the floor of the maxillary sinus. The maxillary first and second molars presented a greater prevalence of alveolar domes, especially in the buccal roots, followed by the third molars and second pre-molars. Although the periapical radiograph is a two-dimensional method, it can provide dentists with the auxiliary information necessary to identify alveolar domes, thus improving diagnosis, planning, and treatment. PMID- 27672616 TI - Contrast reference values in panoramic radiographic images using an arch-form phantom stand. AB - PURPOSE: The purpose of this study was to investigate appropriate contrast reference values (CRVs) by comparing the contrast in phantom and clinical images. MATERIALS AND METHODS: Phantom contrast was measured using two methods: (1) counting the number of visible pits of different depths in an aluminum plate, and (2) obtaining the contrast-to-noise ratio (CNR) for 5 tissue-equivalent materials (porcelain, aluminum, polytetrafluoroethylene [PTFE], polyoxymethylene [POM], and polymethylmethacrylate [PMMA]). Four panoramic radiographs of the contrast phantom, embedded in the 4 different regions of the arch-form stand, and 1 real skull phantom image were obtained, post-processed, and compared. The clinical image quality evaluation chart was used to obtain the cut-off values of the phantom CRV corresponding to the criterion of being adequate for diagnosis. RESULTS: The CRVs were obtained using 4 aluminum pits in the incisor and premolar region, 5 aluminum pits in the molar region, and 2 aluminum pits in the temporomandibular joint (TMJ) region. The CRVs obtained based on the CNR measured in the anterior region were: porcelain, 13.95; aluminum, 9.68; PTFE, 6.71; and POM, 1.79. The corresponding values in the premolar region were: porcelain, 14.22; aluminum, 8.82; PTFE, 5.95; and POM, 2.30. In the molar region, the following values were obtained: porcelain, 7.40; aluminum, 3.68; PTFE, 1.27; and POM, - 0.18. The CRVs for the TMJ region were: porcelain, 3.60; aluminum, 2.04; PTFE, 0.48; and POM, - 0.43. CONCLUSION: CRVs were determined for each part of the jaw using the CNR value and the number of pits observed in phantom images. PMID- 27672617 TI - Interactive learning in oral and maxillofacial radiology. AB - PURPOSE: The use of electronic tools in teaching is growing rapidly in all fields, and there are many options to choose from. We present one such platform, Learning CatalyticsTM (LC) (Pearson, New York, NY, USA), which we utilized in our oral and maxillofacial radiology course for second-year dental students. MATERIALS AND METHODS: The aim of our study was to assess the correlation between students' performance on course exams and self-assessment LC quizzes. The performance of 354 predoctoral dental students from 2 consecutive classes on the course exams and LC quizzes was assessed to identify correlations using the Spearman rank correlation test. The first class was given in-class LC quizzes that were graded for accuracy. The second class was given out-of-class quizzes that were treated as online self-assessment exercises. The grading in the self assessment exercises was for participation only and not accuracy. All quizzes were scheduled 1-2 weeks before the course examinations. RESULTS: A positive but weak correlation was found between the overall quiz scores and exam scores when the two classes were combined (P<0.0001). A positive but weak correlation was likewise found between students' performance on exams and on in-class LC quizzes (class of 2016) (P<0.0001) as well as on exams and online LC quizzes (class of 2017) (P<0.0001). CONCLUSION: It is not just the introduction of technological tools that impacts learning, but also their use in enabling an interactive learning environment. The LC platform provides an excellent technological tool for enhancing learning by improving bidirectional communication in a learning environment. PMID- 27672615 TI - IDIOS: An innovative index for evaluating dental imaging-based osteoporosis screening indices. AB - PURPOSE: The goal of this study was to develop a new index as an objective reference for evaluating current and newly developed indices used for osteoporosis screening based on dental images. Its name; IDIOS, stands for Index of Dental-imaging Indices of Osteoporosis Screening. MATERIALS AND METHODS: A comprehensive PubMed search was conducted to retrieve studies on dental imaging based indices for osteoporosis screening. The results of the eligible studies, along with other relevant criteria, were used to develop IDIOS, which has scores ranging from 0 (0%) to 15 (100%). The indices presented in the studies we included were then evaluated using IDIOS. RESULTS: The 104 studies that were included utilized 24, 4, and 9 indices derived from panoramic, periapical, and computed tomographic/cone-beam computed tomographic techniques, respectively. The IDIOS scores for these indices ranged from 0 (0%) to 11.75 (78.32%). CONCLUSION: IDIOS is a valuable reference index that facilitates the evaluation of other dental imaging-based osteoporosis screening indices. Furthermore, IDIOS can be utilized to evaluate the accuracy of newly developed indices. PMID- 27672619 TI - Developmental salivary gland depression in the ascending mandibular ramus: A cone beam computed tomography study. AB - A static, unilateral, and focal bone depression located lingually within the ascending ramus, identical to the Stafne's bone cavity of the angle of the mandible, is being reported. During development of the mandible, submandibular gland inclusion may lead to the formation of a lingual concavity, which could contain fatty tissue, blood vessels, or soft tissue. However, similar occurrences in the ascending ramus at the level of the parotid gland are extremely rare. Similar cases were previously reported in dry, excavated mandibles, and 3 cases were reported in living patients. A 52-year-old African American male patient was seen for pain in the mandibular teeth. Panoramic radiography showed an unusual concavity within the left ascending ramus. Cone-beam computed tomography confirmed this incidental finding. The patient was cleared for the extraction of non-restorable teeth and scheduled for annual follow-up. PMID- 27672618 TI - Post-traumatic bifid mandibular condyle: A case report and literature review. AB - Bifid mandibular condyle (BMC) is an uncommon morphological variant of the mandibular condyle. Although authors have proposed various etiologies for BMC, no consensus has emerged. In addition, varying findings have been reported regarding the epidemiological parameters of BMC (e.g., prevalence, gender ratio, and age), possibly due to its low incidence. BMC is occasionally associated with symptoms of the temporomandibular joint, such as ankylosis, pain, and trismus; however, it is difficult to detect this condition on conventional radiographs. This study reports a case of BMC with radiographic findings, and reviews the literature on the epidemiology of BMC. PMID- 27672621 TI - Incidence, Treatment, and Survival Patterns for Sacral Chordoma in the United States, 1974-2011. AB - INTRODUCTION: Sacral chordomas represent one half of all chordomas, a rare neoplasm of notochordal remnants. Current NCCN guidelines recommend surgical resection with or without adjuvant radiotherapy or definitive radiation for unresectable cases. Recent advances in radiation for chordomas include conformal photon and proton beam radiation. We investigated incidence, treatment, and survival outcomes to observe any trends in response to improvements in surgical and radiation techniques over a near 40-year time period. MATERIALS AND METHODS: Three hundred forty-five microscopically confirmed cases of sacral chordoma were identified between 1974 and 2011 from the surveillance, epidemiology, and end results program of the National Cancer Institute. Cases were divided into three cohorts by calendar year, 1974-1989, 1990-1999, and 2000-2011, as well as into two groups by age <=65 versus >65 to investigate trends over time and age via Chi square analysis. Kaplan-Meier analyses were performed to determine effects of treatment on survival. Multivariate Cox regression analysis was performed to determine predictors of overall survival (OS). RESULTS: Five-year OS for the entire cohort was 60.0%. OS correlated significantly with treatment modality, with 44% surviving at 5 years with no treatment, 52% with radiation alone, 82% surgery alone, and 78% surgery and radiation (p < 0.001). Age >65 was significantly associated with non-surgical management with radiation alone or no treatment (p < 0.001). Relatively, fewer patients received radiation between 2000 and 2011 compared to prior time periods (p = 0.03) versus surgery, for which rates which did not vary significantly over time (p = 0.55). However, 5-year OS was not significantly different by time period. Age group and treatment modality were predictive for OS on multivariate analysis (p < 0.001). CONCLUSION: Surgery remains an important component in the treatment of sacral chordomas in current practice. Fewer patients were treated with radiation more recently despite advances in photon and proton beam radiation. OS remains unchanged. Additional analyses of margin status, radiation modality, and local control in current practice are warranted. PMID- 27672620 TI - How Can Physical Activity Referral Rates for Breast Cancer Patients be Increased? PMID- 27672622 TI - Two Glycosyltransferase Genes of Haemophilus parasuis SC096 Implicated in Lipooligosaccharide Biosynthesis, Serum Resistance, Adherence, and Invasion. AB - Haemophilus parasuis is a common opportunistic pathogen known for its ability to colonize healthy piglets and causes Glasser's disease. The lipooligosaccharide (LOS) of H. parasuis is a potential virulence-associated factor. In this study, two putative glycosyltransferases that might be involved in LOS synthesis in H. parasuis SC096 were identified (lgtB and lex-1). Mutants were constructed to investigate the roles of the lgtB and lex-1 genes. The LOS from the DeltalgtB or Deltalex-1 mutant showed truncated structure on silver-stained SDS-PAGE gel compared to the wild-type strain. The DeltalgtB and Deltalex-1 mutants were significantly more sensitive to 50% porcine serum, displaying 15.0 and 54.46% survival rates, respectively. Complementation of the lex-1 mutant restored the serum-resistant phenotype. Additionally, the DeltalgtB and Deltalex-1 strains showed impaired ability to adhere to and invade porcine kidney epithelial cells (PK-15). The above results suggested that the lgtB and lex-1 genes of the H. parasuis SC096 strain participated in LOS synthesis and were involved in serum resistance, adhesion and invasion. PMID- 27672624 TI - Deep Brain Stimulation and Gene Expression Alterations in Parkinson's Disease. PMID- 27672623 TI - N-acetylgalatosamine-Mediated Regulation of the aga Operon by AgaR in Streptococcus pneumoniae. AB - Here, we analyze the transcriptomic response of Streptococcus pneumoniae D39 to N acetylgalactosamine (NAGa). Transcriptome comparison of S. pneumoniae D39 grown in NAGaM17 (0.5% NAGa + M17) to that grown in GM17 (0.5% Glucose + M17) revealed the elevated expression of various carbon metabolic genes/operons, including a PTS operon (denoted here as the aga operon), which is putatively involved in NAGa transport and utilization, in the presence of NAGa. We further studied the role of a GntR-family transcriptional regulator (denoted here as AgaR) in the regulation of aga operon. Our transcriptome and RT-PCR data suggest the role of AgaR as a transcriptional repressor of the aga operon. We predicted a 20-bp operator site of AagR (5'-ATAATTAATATAACAACAAA-3') in the promoter region of the aga operon (PbgaC), which was further verified by mutating the AgaR operator site in the respective promoter. The role of CcpA in the additional regulation of the aga operon was elucidated by further transcriptome analyses and confirmed by quantitative RT-PCR. PMID- 27672625 TI - Skin Dosimetry in Radiotherapy of Breast Cancer: a Comparison between EBT and EBT3 Radiochromic Films. AB - OBJECTIVE: Radiochromic EBT3 film is a later generation of radiochromic films. The aim of this study is to compare EBT and EBT3 radiochromic films in radiotherapy fields of breast cancer. METHODS: A RANDO phantom was irradiated by a 6 MV Siemens Primus linac with medial and lateral fields of radiotherapy of breast cancer. Dosimetry was performed in various points in the fields using EBT and EBT3 films. Films were scanned by a Microtek color scanner. Dose values from two films in corresponding points were compared. RESULTS: In the investigation of calibration, net optical density (NOD) of EBT radiochromic is more than the EBT3 radiochromic film. The highest percentage difference between NODs of two films is related to 0.75 Gy and equals to 14.19%. The lowest value is related to 0.2 Gy dose and is equal to 3.31%. The highest percentage difference between two films on the RANDO phantom in breast cancer fields is 13.51% and the minimum value is equal to 0.33%. CONCLUSION: From the comparison between the two films, most of the points show differences in dose in the measurements in fields of breast cancer radiotherapy. These differences are attributed to the thickness of the active layers, the overall thickness of the films, and the difference in the calibration fitted functions. The advantage of EBT film over EBT3 is a higher sensitivity; on the other hand EBT3 film allows to use its both sides in the scanning process and it is a new version of this film type. PMID- 27672626 TI - Local-Reference Patient Dose Evaluation in Conventional Radiography Examinations in Mazandaran, Iran. AB - BACKGROUND: The most efficient application of ionizing radiation is serving medical purposes and using this radiation has caused people to learn that artificial sources of radiation exposure among these resources can be of highest exposure rate. OBIECTIVE: The present study is aimed at initially establishing a baseline for local-reference dose level in Mazandaran, Iran in 12 projections of the most conventional x-ray examination. METHODS: In this study, 13 public hospitals in Mazandaran province were selected for review and required data collected for ten adult patients with mean weight of 70+/-10kg in each projection. Then, information of each center was separately analyzed. Next, in order to measure x-ray output tube, the dosimeter RTI model Barracuda calibrated has been applied for measuring air karma within energy rage of 40-150kvp. ESAK and ESD parameters, usually used for monitoring DRL in conventional radiography, were calculated. RESULTS: Mean ESDs in this study has been obtained to 1.47+/ 0.98 for skull (PA/AP), 1.01+/-0.79 for skull (LAT), 0.67+/-0.38 for cervical spine (AP), 0.79+/-0.37 for cervical (LAT), 0.49+/-0.38 for chest (PA/AP), 1.06+/ 0.44 for chest (LAT), 2.15+/-0.73 for thoracic spine (AP), 3+/-0.87 for thoracic spine (LAT), 2.81 +/-0.82 for lumbar spine (AP), 4.28+/-0.78 for lumbar (LAT), 2.07+/-1.17 for abdomen and 1.90+/-0.99 for pelvis, respectively. The ESDs calculated for chest examination in both projections, PA and LAT are more than values recommended by the UK (2000), Brazil and Slovenia. CONCLUSION: The present study has determined wide variations in radiation dose of x-ray examinations among hospitals in Mazandaran, Iran. In order to reduce skin dose, an optimization procedure should be considered. Application of a reference dose (DRL) could be a practical method for this purpose. The role of optimization of radiography parameters for reducing patient dose is a significant issue. Through optimizing parameters, it would be possible to preserve image quality while reduction of patient dose. PMID- 27672628 TI - Optimized Seizure Detection Algorithm: A Fast Approach for Onset of Epileptic in EEG Signals Using GT Discriminant Analysis and K-NN Classifier. AB - BACKGROUND: Epilepsy is a severe disorder of the central nervous system that predisposes the person to recurrent seizures. Fifty million people worldwide suffer from epilepsy; after Alzheimer's and stroke, it is the third widespread nervous disorder. OBJECTIVE: In this paper, an algorithm to detect the onset of epileptic seizures based on the analysis of brain electrical signals (EEG) has been proposed. 844 hours of EEG were recorded form 23 pediatric patients consecutively with 163 occurrences of seizures. Signals had been collected from Children's Hospital Boston with a sampling frequency of 256 Hz through 18 channels in order to assess epilepsy surgery. By selecting effective features from seizure and non-seizure signals of each individual and putting them into two categories, the proposed algorithm detects the onset of seizures quickly and with high sensitivity. METHOD: In this algorithm, L-sec epochs of signals are displayed in form of a third-order tensor in spatial, spectral and temporal spaces by applying wavelet transform. Then, after applying general tensor discriminant analysis (GTDA) on tensors and calculating mapping matrix, feature vectors are extracted. GTDA increases the sensitivity of the algorithm by storing data without deleting them. Finally, K-Nearest neighbors (KNN) is used to classify the selected features. RESULTS: The results of simulating algorithm on algorithm standard dataset shows that the algorithm is capable of detecting 98 percent of seizures with an average delay of 4.7 seconds and the average error rate detection of three errors in 24 hours. CONCLUSION: Today, the lack of an automated system to detect or predict the seizure onset is strongly felt. PMID- 27672627 TI - Evaluation of Soft Tissue Sarcoma Tumors Electrical Conductivity Anisotropy Using Diffusion Tensor Imaging for Numerical Modeling on Electroporation. AB - INTRODUCTION: There is many ways to assessing the electrical conductivity anisotropy of a tumor. Applying the values of tissue electrical conductivity anisotropy is crucial in numerical modeling of the electric and thermal field distribution in electroporation treatments. This study aims to calculate the tissues electrical conductivity anisotropy in patients with sarcoma tumors using diffusion tensor imaging technique. MATERIALS AND METHOD: A total of 3 subjects were involved in this study. All of patients had clinically apparent sarcoma tumors at the extremities. The T1, T2 and DTI images were performed using a 3 Tesla multi-coil, multi-channel MRI system. The fractional anisotropy (FA) maps were performed using the FSL (FMRI software library) software regarding the DTI images. The 3D matrix of the FA maps of each area (tumor, normal soft tissue and bone/s) was reconstructed and the anisotropy matrix was calculated regarding to the FA values. RESULT: The mean FA values in direction of main axis in sarcoma tumors were ranged between 0.475-0.690. With assumption of isotropy of the electrical conductivity, the FA value of electrical conductivity at each X, Y and Z coordinate axes would be equal to 0.577. The gathered results showed that there is a mean error band of 20% in electrical conductivity, if the electrical conductivity anisotropy not concluded at the calculations. The comparison of FA values showed that there is a significant statistical difference between the mean FA value of tumor and normal soft tissues (P<0.05). CONCLUSION: DTI is a feasible technique for the assessment of electrical conductivity anisotropy of tissues. It is crucial to quantify the electrical conductivity anisotropy data of tissues for numerical modeling of electroporation treatments. PMID- 27672629 TI - Improving Brain Magnetic Resonance Image (MRI) Segmentation via a Novel Algorithm based on Genetic and Regional Growth. AB - BACKGROUND: Regarding the importance of right diagnosis in medical applications, various methods have been exploited for processing medical images solar. The method of segmentation is used to analyze anal to miscall structures in medical imaging. OBJECTIVE: This study describes a new method for brain Magnetic Resonance Image (MRI) segmentation via a novel algorithm based on genetic and regional growth. METHODS: Among medical imaging methods, brains MRI segmentation is important due to high contrast of non-intrusive soft tissue and high spatial resolution. Size variations of brain tissues are often accompanied by various diseases such as Alzheimer's disease. As our knowledge about the relation between various brain diseases and deviation of brain anatomy increases, MRI segmentation is exploited as the first step in early diagnosis. In this paper, regional growth method and auto-mate selection of initial points by genetic algorithm is used to introduce a new method for MRI segmentation. Primary pixels and similarity criterion are automatically by genetic algorithms to maximize the accuracy and validity in image segmentation. RESULTS: By using genetic algorithms and defining the fixed function of image segmentation, the initial points for the algorithm were found. The proposed algorithms are applied to the images and results are manually selected by regional growth in which the initial points were compared. The results showed that the proposed algorithm could reduce segmentation error effectively. CONCLUSION: The study concluded that the proposed algorithm could reduce segmentation error effectively and help us to diagnose brain diseases. PMID- 27672630 TI - A Nano-indentation Identification Technique for Viscoelastic Constitutive Characteristics of Periodontal Ligaments. AB - INTRODUCTION: Nano-indentation has recently been employed as a powerful tool for determining the mechanical properties of biological tissues on nano and micro scales. A majority of soft biological tissues such as ligaments and tendons exhibit viscoelastic or time-dependent behaviors. The constitutive characterization of soft tissues is among very important subjects in clinical medicine and especially, biomechanics fields. Periodontal ligament plays an important role in initiating tooth movement when loads are applied to teeth with orthodontic appliances. It is also the most accessible ligament in human body as it can be directly manipulated without any surgical intervention. From a mechanical point of view, this ligament can be considered as a thin interface made by a solid phase, consisting mainly of collagen fibers, which is immersed into a so-called ground substance. However, the viscoelastic constitutive effects of biological tissues are seldom considered rigorous during Nano-indentation tests. METHODS: In the present paper, a mathematical contact approach is developed to enable determining creep compliance and relaxation modulus of distinct periodontal ligaments, using constant-rate indentation and loading time histories, respectively. An adequate curve-fitting method is presented to determine these characteristics based on the Nano-indentation of rigid Berkovich tips. Generalized Voigt-Kelvin and Wiechert models are used to model constitutive equations of periodontal ligaments, in which the relaxation and creep functions are represented by series of decaying exponential functions of time. RESULTS: Time-dependent creep compliance and relaxation function have been obtained for tissue specimens of periodontal ligaments. CONCLUSION: To improve accuracy, relaxation and creep moduli are measured from two tests separately. Stress relaxation effects appear more rapidly than creep in the periodontal ligaments. PMID- 27672631 TI - Pulsed Intra-Arterial Drug Injection during Diastolic Phase of Cardiac Function Increases Drug Efficacy by Enhancing Pharmacological Exposure of Targeted Tissues. AB - Diastolic phase of cardiac function is associated with lower arterial flow and hence higher concentration of intra arterially injected drug is achieved at the site of injection. It is herein postulated that drugs show higher efficacy when injected during the diastolic phase of cardiac function. It is also postulated that this benefit cannot be achieved when the drug is injected with higher rates thus producing the same high concentration at the site of injection. Pulsed intra arterial injection also benefits from the delayed therapeutic effect of the decaying drug before the next shot of injection resaturates the targeted tissue. Altogether, it is estimated that diastolic time-locked pulsed intra arterial injection will increase the drug efficacy up to 1.9 times the efficacy of injected drug with conventional methods. This is significant for drugs with limited dose of administration due to their disastrous side effects like tissue plasminogen activator or chemotherapeutic drugs. PMID- 27672632 TI - Comparison of Brain Development in Sow-Reared and Artificially Reared Piglets. AB - INTRODUCTION: Provision of adequate nutrients is critical for proper growth and development of the neonate, yet the impact of breastfeeding versus formula feeding on neural maturation has to be fully determined. Using the piglet as a model for the human infant, our objective was to compare neurodevelopment of piglets that were either sow-reared (SR) or artificially reared (AR) in an artificial setting. METHODS: Over a 25-day feeding study, piglets (1.5 +/- 0.2 kg initial bodyweight) were either SR (n = 10) with ad libitum intake or AR (n = 29) receiving an infant formula modified to mimic the nutritional profile and intake pattern of sow's milk. At study conclusion, piglets were subjected to a standardized set of magnetic resonance imaging (MRI) procedures to quantify structure and composition of the brain. RESULTS: Diffusion tensor imaging, an MRI sequence that characterizes brain microstructure, revealed that SR piglets had greater (P < 0.05) average white matter (WM) (generated from a piglet specific brain atlas) fractional anisotropy (FA), and lower (P < 0.05) mean and radial and axial diffusivity values compared with AR piglets, suggesting differences in WM organization. Voxel-based morphometric analysis, a measure of white and gray matter (GM) volumes concentrations, revealed differences (P < 0.05) in bilateral development of GM clusters in the cortical brain regions of the AR piglets compared with SR piglets. Region of interest analysis revealed larger (P < 0.05) whole brain volumes in SR animals compared with AR, and certain subcortical regions to be larger (P < 0.05) as a percentage of whole brain volume in AR piglets compared with SR animals. Quantification of brain metabolites using magnetic resonance spectroscopy revealed SR piglets had higher (P < 0.05) concentrations of myo-inositol, glycerophosphocholine + phosphocholine, and creatine + phosphocreatine compared with AR piglets. However, glutamate + glutamine levels were higher (P < 0.05) in AR piglets when compared with SR animals. CONCLUSION: Overall, increases in brain metabolite concentrations, coupled with greater FA values in WM tracts and volume differences in GM of specific brain regions, suggest differences in myelin development and cell proliferation in SR versus AR piglets. PMID- 27672633 TI - A Scoping Review of Tailored Self-management Interventions among Adults with Mobility Impairing Neurological and Musculoskeletal Conditions. AB - A critical public health objective is to optimize and disseminate self-management interventions for the 56.7 million adults living with chronic disabling conditions in the United States. A possible strategy to optimize the effectiveness of self-management interventions is to understand how best to tailor self-management interventions to the needs and circumstances of each participant. Thus, the purpose of this scoping review was to describe randomized controlled trials (RCTs) of tailored self-management interventions in adults with neurological and musculoskeletal conditions that characteristically result in mobility impairments. The 13 RCTs included in the scoping review typically compared tailored interventions to non-tailored interventions or usual care among adults with chronic pain, stroke, and/or arthritis. The tailored interventions were diverse in their delivery formats, dosing, behavior change techniques, and tailoring strategies. We identified 13 personal characteristics (e.g., preferences and theoretical constructs) and 4 types of assessment formats (i.e., oral history, self-report questionnaires, provider-reported assessments, and medical records) that were used to tailor the self-management interventions. It was common to tailor intervention content using self-report questionnaires that assessed personal characteristics pertaining to impairments and preferences. Content was matched to personal characteristics using clinical judgment or computer algorithms. However, few studies adequately described the decision rules for matching content. To advance the science of tailoring self-management interventions, we recommend conducting comparative effectiveness research and further developing a taxonomy to standardize descriptions of tailoring. We discuss the opportunities that are now coalescing to optimize tailored self management. We also provide examples of how to merge concepts from the self management literature with conceptual frameworks of tailoring from the health communication literature. PMID- 27672634 TI - Impact of Demographic, Socioeconomic, and Psychological Factors on Glycemic Self Management in Adults with Type 2 Diabetes Mellitus. AB - Diabetes mellitus (DM) is reported as one of the most complex chronic diseases worldwide. In the United States, Type 2 DM (T2DM) is the seventh leading cause of morbidity and mortality. Individuals with diabetes require lifelong personal care to reduce the possibility of developing long-term complications. A good knowledge of diabetes risk factors, including obesity, dyslipidemia, hypertension, family history of DM, and sedentary lifestyle, play an essential role in prevention and treatment. Also, sociodemographic, economic, psychological, and environmental factors are directly and indirectly associated with diabetes control and health outcomes. Our review intends to analyze the interaction between demographics, knowledge, environment, and other diabetes-related factors based on an extended literature search, and to provide insight for improving glycemic control and reducing the incidence of chronic complications. PMID- 27672637 TI - Challenges in Molecular Diagnostics of Channelopathies in the Next-Generation Sequencing Era: Less Is More? PMID- 27672635 TI - Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition. AB - Communication within the immune system depends on the release of factors that can travel and transmit information at points distant from the cell that produced them. In general, immune cells use two key strategies that can occur either at the plasma membrane or in intracellular compartments to produce such factors, vesicle release and proteolytic cleavage. Release of soluble factors in exosomes, a subset of vesicles that originate from intracellular compartments, depends generally on biochemical and lipid environment features. This physical environment allows proteins to be recruited to membrane microdomains that will be later endocytosed and further released to the extracellular milieu. Cholesterol and sphingolipid rich domains (also known as lipid rafts or detergent-resistant membranes, DRMs) often contribute to exosomes and these membrane regions are rich in proteins modified with Glycosyl-Phosphatidyl-Inositol (GPI) and lipids. For this reason, many palmitoylated and GPI-anchored proteins are preferentially recruited to exosomes. In this review, we analyse the biochemical features involved in the release of NKG2D-ligands as an example of functionally related gene families encoding both transmembrane and GPI-anchored proteins that can be released either by proteolysis or in exosomes, and modulate the intensity of the immune response. The immune receptor NKG2D is present in all human Natural Killer and T cells and plays an important role in the first barrier of defense against tumor and infection. However, tumor cells can evade the immune system by releasing NKG2D-ligands to induce down-regulation of the receptor. Some NKG2D ligands can be recruited to exosomes and potently modulate receptor expression and immune function, while others are more susceptible to metalloprotease cleavage and are shed as soluble molecules. Strikingly, metalloprotease inhibition is sufficient to drive the accumulation in exosomes of ligands otherwise released by metalloprotease cleavage. In consequence, NKG2D-ligands appear as different entities in different cells, depending on cellular metabolism and biochemical structure, which mediate different intensities of immune modulation. We discuss whether similar mechanisms, depending on an interplay between metalloprotease cleavage and exosome release, could be a more general feature regulating the composition of exosomes released from human cells. PMID- 27672636 TI - Melusin Promotes a Protective Signal Transduction Cascade in Stressed Hearts. AB - Melusin is a chaperone protein selectively expressed in heart and skeletal muscles. Melusin expression levels correlate with cardiac function in pre clinical models and in human patients with aortic stenosis. Indeed, previous studies in several animal models indicated that Melusin plays a broad cardioprotective role in different pathological conditions. Chaperone proteins, besides playing a role in protein folding, are also able to facilitate supramolecular complex formation and conformational changes due to activation/deactivation of signaling molecules. This role sets chaperone proteins as crucial regulators of intracellular signal transduction pathways. In particular Melusin activates AKT and ERK1/2 signaling, protects cardiomyocytes from apoptosis and induces a compensatory hypertrophic response in several pathological conditions. Therefore, selective delivery of the Melusin gene in heart via cardiotropic adenoviral associated virus serotype 9 (AAV9), may represent a new promising gene-therapy approach for different cardiac pathologies. PMID- 27672639 TI - 450 nm diode laser: A new help in oral surgery. AB - AIM: To describe the performance of 450 nm diode laser in oral surgery procedures. METHODS: The case described consisted of the removal of a lower lip fibroma through a blue diode laser (lambda = 450 nm). RESULTS: The efficacy of this device, even at very low power (1W, CW), allows us to obtain very high intra and postoperative comfort for the patient, even with just topical anaesthesia and without needing suture. The healing process was completed in one week and, during the follow-up, the patient did not report any problems, pain or discomfort even without the consumption of any kind of drugs, such as painkillers and antibiotics. The histological examination performed by the pathologist showed a large area of fibrous connective tissue with some portions of epithelium connective detachments and a regular incision with very scanty areas of carbonization. CONCLUSION: The 450 nm diode laser proved of being very efficient in the oral soft tissue surgical procedures, with no side effects for the patients. PMID- 27672640 TI - Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and treatment response. AB - Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone (commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intra-abdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy. PMID- 27672638 TI - Multiple Infectious Agents and the Origins of Atherosclerotic Coronary Artery Disease. AB - Although deaths due to atherosclerotic coronary artery disease (ACAD) have fallen dramatically during the past 50 years, ACAD remains as the leading cause of death in all continents, except Africa, where deaths due to infections are still dominant. Although food and nutrition have a proven role in atherosclerosis, the underlying causes of ACAD remain unknown. This is despite a century of intensive research dominated by investigations into the saturated fat hypothesis. In this review, it is hypothesized that the rise and fall in ACAD during the past 100 years is primarily due to the parallel rise and fall in the prevalence of coronary atheroma, the underlying disease. It is further hypothesized that infectious pathogens initiate atherosclerosis mainly during infancy and childhood. It is speculated that widespread use of antibiotics and vaccines against bacterial and viral infections may be the reason for the dramatic fall in coronary atheroma and ACAD during the past 50 years. The relevant evidence and a working hypothesis are included in this review. PMID- 27672642 TI - Incidentally detected hydatid cyst of the adrenal gland: A case report. AB - Hydatid cysts are a zoonotic disease that can involve many organs and tissues in the human body but primarily involve the liver and lungs. Of the main organs, adrenal glands are those seldom affected by hydatid cysts. The purpose of this study was to present a case with an incidentally detected hydatid cyst of the right adrenal gland on computed tomography, and a positive echincoccus IgG enzyme linked immunosorbent assay test on top of a toxic multinodular thyroid goiter for which thyroidectomy was indicated. PMID- 27672641 TI - Small bowel entrapment and ureteropelvic junction disruption associated with L3 Chance fracture-dislocation. AB - Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disruption associated with a Chance fracture and spine dislocation following a traffic accident. Initial X rays and computed tomographic (CT) scan showed a Chance fracture with dislocation of L3 vertebra, with an incarceration of a small bowel loop in the spinal canal and a complete section of the left lumbar ureter. Paraplegia was noticed on the initial neurological examination. A posterior L2-L4 osteosynthesis was performed firstly. In a second time she underwent a sus umbilical laparotomy to release the incarcerated jejunum loop in the spinal canal. An end-to-end anastomosis was performed on a JJ probe to suture the left injured ureter. One month after the traumatism, she started to complain of severe headaches related to a leakage of cerebrospinalis fluid. Three months after the traumatism there was a clear regression of the leakage. One year after the trauma, an anterior intervertebral fusion was done. At final follow-up, no neurologic recovery was noticed. In case of Chance fracture, all physicians should think about abdominal injuries even if the patient is asymptomatic. Initial abdominal CT scan and magnetic resonance imaging provide in such case crucial info for management of the spine and the associated lesions. PMID- 27672643 TI - Tuberculosis terminal ileitis: A forgotten entity mimicking Crohn's disease. AB - Intestinal tuberculosis (TB) is an uncommon lesion for which differential diagnosis can be difficult. We present a case of a 53-year-old male and a systematic review of the literature, from clinical symptoms to differential diagnosis, unusual complications and therapy. The patient was admitted to the hospital with signs of acute abdomen as a result of a perforated terminal ileitis. Based on the skip lesions of the terminal ileum and cecum, Crohn's disease (CD) was clinically suspected. An emergency laparotomy and right colectomy with terminal ileum resection was performed and systematic antibiotherapy was prescribed. The patient's status deteriorated and he died 4 d after the surgical intervention. At the autopsy, TB ileotyphlitis was discovered. The clinical criteria of the differential diagnosis between intestinal TB and CD are not very well established. Despite the large amount of published articles on this subject, only 50 papers present new data regarding intestinal TB. Based on these studies and our experience, we present an update focused on the differential diagnosis and therapy of intestinal TB. We highlight the importance of considering intestinal TB as a differential diagnosis for inflammatory bowel disease. Despite the modern techniques of diagnosis and therapy, the fulminant evolution of TB can still lead to a patient's death. PMID- 27672644 TI - Cystic jejunal duplication with Heinrich's type I ectopic pancreas, incidentally discovered in a patient with pancreatic tail neoplasm. AB - The aim of this study was to present a case of enteric duplication cyst and criteria for a proper differential diagnosis. A 51-year-old male was hospitalized for pancreatic tail neoplasm and distal pancreatectomy with splenectomy was performed. During surgery, a jejunal cystic lesion was incidentally detected and jejunectomy was performed. Microscopically, the cyst was observed to be covered by Keratin 7/Keratin 20 positive intestinal type epithelium and the muscularis layer was shared by the cyst and adjacent jejunum, without a cleavage plane between the cyst wall and jejunal muscularis propria. In the deep muscularis propria, a Heinrich's type I ectopic pancreas was also noted. In the pancreatic tail, a low grade intraepithelial lesion (panIN-1a) was diagnosed. This case highlights the necessity for a correct differential diagnosis of such rare lesions. Roughly 30 cases of jejunal duplication cysts have been reported to date in the PubMed database. PMID- 27672645 TI - Tooth loss caused by displaced elastic during simple preprosthetic orthodontic treatment. AB - The use of elastics to close a diastema or correct tooth malpositions can create unintended consequences if not properly controlled. The American Association of Orthodontists recently issued a consumer alert, warning of "a substantial risk for irreparable damage" from a new trend called "do-it-yourself" orthodontics, consisting of patients autonomously using elastics to correct tooth position. The elastics can work their way below the gums and around the roots of the teeth, causing damage to the periodontium and even resulting in tooth loss. The cost of implants to replace these teeth would well exceed the cost of proper orthodontic care. This damage could also occur in a dental office, when a general dentist tries to perform a simplified orthodontic correction of a minor tooth malposition. The present case report describes a case of tooth loss caused by a displaced intraoral elastic, which occurred during a simple preprosthetic orthodontic treatment. PMID- 27672646 TI - Surgical treatment of cementoblastoma associated with apicoectomy and endodontic therapy: Case report. AB - This case report describes the surgical removal of cementoblastoma associated with apicoectomy and endodontic therapy. The patient, an 18-year-old man, presented pain in the region of the mandibular body on the right side. On clinical exam, bone expansion was observed in the region at the bottom of the vestibular sulcus, pain on palpation, slight extrusion of tooth 46 with presence of pulp vitality. Radiographic exams demonstrated the presence of a radiopaque area and discrete radiolucent halo associated with the root of tooth 46, suggesting the diagnosis of cementoblastoma. Endodontic treatment of tooth 46 was performed and exeresis of the lesion by apicoectomy. Twelve months after the first surgery, recurrence of the lesion was observed, and a new apicoectomy was necessary, this time up to the middle third of the root. Clinical radiographic control 12 mo after the second surgical intervention demonstrated absence of signs and symptoms, radiographic repair, with tooth 46 shown to be fully functional. PMID- 27672647 TI - Unique case of oligoastrocytoma with recurrence and grade progression: Exhibiting differential expression of high mobility group-A1 and human telomerase reverse transcriptase. AB - Mixed gliomas, primarily oligoastrocytomas, account for about 5%-10% of all gliomas. Distinguishing oligoastrocytoma based on histological features alone has limitations in predicting the exact biological behavior, necessitating ancillary markers for greater specificity. In this case report, human telomerase reverse transcriptase (hTERT) and high mobility group-A1 (HMGA1); markers of proliferation and stemness, have been quantitatively analyzed in formalin-fixed paraffin-embedded tissue samples of a 34 years old patient with oligoastrocytoma. Customized florescence-based immunohistochemistry protocol with enhanced sensitivity and specificity is used in the study. The patient presented with a history of generalized seizures and his magnetic resonance imaging scans revealed infiltrative ill-defined mass lesion with calcified foci within the left frontal white matter, suggestive of glioma. He was surgically treated at our center for four consecutive clinical events. Histopathologically, the tumor was identified as oligoastrocytoma-grade II followed by two recurrence events and final progression to grade III. Overall survival of the patient without adjuvant therapy was more than 9 years. Glial fibrillary acidic protein, p53, Ki-67, nuclear atypia index, pre-operative neutrophil-lymphocyte ratio, are the other parameters assessed. Findings suggest that hTERT and HMGA1 are linked to tumor recurrence and progression. Established markers can assist in defining precise histopathological grade in conjuction with conventional markers in clinical setup. PMID- 27672648 TI - Gliosarcoma: A rare variant of glioblastoma multiforme in paediatric patient: Case report and review of literature. AB - Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5(th) and 6(th) decades of life and extremely rare in children. It is highly aggressive tumour and managed like glioblastoma multiforme. A 12-year-old female child presented with complaints of headache and vomiting from 15 d and blurring of vision from 3 d. Magnetic resonance imaging of brain shows heterogeneous mass in right parieto-occipital cortex. A right parieto-occipito-temporal craniotomy with complete excision of mass revealed a primary glioblastoma on histopathological investigation. Treatment consists of maximum surgical excision followed by adjuvant radiotherapy. The etiopathogenesis, treatment modalities and prognosis is discussed. The available literature is also reviewed. PMID- 27672649 TI - Huge peripheral primitive neuroectodermal tumor of the small bowel mesentery at nonage: A case report and review of the literature. AB - Extraskeletal Ewing's sarcoma/peripheral primitive neuroectodermal tumor (E EWS/pPNET) is a rare aggressive malignant small round cell tumor. In this report, we present the case of a 15-year-old boy who suffered from acute abdominal pain accompanied by hematemesis and melena, and was eventually diagnosed with E EWS/pPNET. To date, there have been only five reported cases of E-EWS/pPNET of the small bowel including the patient in this report. To the best of our knowledge, this is the first documentation of a pPNET of the small bowel mesentery at nonage. All these have made this report rare and significant. PMID- 27672650 TI - Evaluation of Knee Proprioception and Factors Related to Parkinson's Disease. AB - Background. Changes in proprioception may contribute to postural instability in individuals with neurological disorders. Objectives. Evaluate proprioception in the lower limbs of patients with Parkinson's disease (PD) and the association between proprioception and cognitive ability, motor symptoms, postural instability, and disease severity. Methods. This is a cross-sectional, controlled study that evaluated proprioception in PD patients and healthy age- and sex matched individuals. Kinetic postural proprioception of the knee was evaluated using an isokinetic dynamometer (Biodex(r) Multi-Joint System 4 Pro). Participants were evaluated using the Montreal Cognitive Assessment (MoCA), the Hoehn and Yahr rating scale and postural instability (pull test and stabilometric analysis), and motor function (UPDRS-III) tests. Results. A total of 40 individuals were enrolled in the study: 20 PD patients and 20 healthy controls (CG). The PD patients had higher angular errors on the proprioceptive ratings than the CG participants (p = 0.002). Oscillations of the center of pressure (p = 0.002) were higher in individuals with PD than in the controls. Proprioceptive errors in the PD patients were associated with the presence of tremors as the dominant symptom and more impaired motor performance. Conclusion. These findings show that individuals with PD have proprioceptive deficits, which are related to decreased cognitive ability and impaired motor symptoms. PMID- 27672652 TI - RNA-Seq Analysis Reveals Candidate Targets for Curcumin against Tetranychus cinnabarinus. AB - Tetranychus cinnabarinus is an important agricultural pest with a broad host range. We previously identified curcumin as a promising acaricidal compound against T. cinnabarinus. However, the acaricidal mechanism of curcumin remains unknown. In this study, RNA-seq was employed to analyze the transcriptome changes in T. cinnabarinus treated with curcumin or the solvent. A total of 105,706,297 clean sequence reads were generated by sequencing, with more than 90% of the reads successfully mapped to the reference sequence. The RNA-seq identified 111 and 96 differentially expressed genes between curcumin- and solvent-treated mites at 24 and 48 h after treatment, respectively. GO enrichment analysis of differentially expressed genes showed that the cellular process was the dominant group at both time points. Finally, we screened 23 differentially expressed genes that were functionally identical or similar to the targets of common insecticide/acaricides or genes that were associated with mite detoxification and metabolism. Calmodulin, phospholipase A2, and phospholipase C were activated upon curcumin treatment suggesting that the calcium channel related genes might play important roles in mite's response to curcumin. Overall our results revealed the global transcriptional changes in T. cinnabarinus after curcumin treatment to enable further identification of the targets of curcumin in mites. PMID- 27672651 TI - Evaluation of Light-Activated Provisional Resin Materials for Periodontal Soft Tissue Management. AB - The purpose of this study was to determine mechanical properties using a compressive test with cylinder specimen (h = 6 mm and phi = 4 mm) as well as cytotoxicity using elutes from disk specimen (phi = 10 mm and h = 2 mm) against human gingival fibroblasts and oral keratinocytes with light-activated provisional resin materials (Revotek LC and Luxatemp Solar) compared to chemically activated counterpart (Snap, Trim II, and Jet). Significantly increased compressive strength (210~280 MPa) was detected in light-activated products compared to chemically activated ones (20~65 MPa, P < 0.05) and similar compressive modulus was detected in both types (0.8~1.5 and 0.5~1.3 GPa). Simultaneously, the light-activated products showed less adverse effects on the periodontal soft tissue cells in any polymerization stage compared to the chemically activated products. Particularly, chemically activated products had significantly greater adverse effects during the "polymerizing" phase compared to those that were "already set" (P < 0.05), as shown in confocal microscopic images of live and dead cells. In conclusion, light-activated provisional resin materials have better mechanical properties as well as biocompatibility against two tested types of oral cells compared to the chemically activated counterpart, which are considered as more beneficial choice for periodontal soft tissue management. PMID- 27672653 TI - Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1. AB - Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome. PMID- 27672654 TI - Minimally Invasive Spinal Surgery. PMID- 27672655 TI - Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis. AB - The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 MUg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury. PMID- 27672656 TI - The Significance of Long Noncoding RNA H19 in Predicting Progression and Metastasis of Cancers: A Meta-Analysis. AB - Recently, numerous studies indicate that H19 plays a key role in tumorigenesis, but the results have been disputed, especially in the aspects of tumor progression and metastasis. Therefore, we performed this meta-analysis to systematically summarize the relationship between H19 and cancers. We searched PubMed, the Cochrane Library, CNKI, and Chinese Wan Fang to identify eligible studies. Odds ratios and 95% confidence intervals were calculated to assess the effect size. A total of 13 studies were enrolled in this meta-analysis, which was performed by Revman5.3 and Stata11.0 software. Our meta-analysis showed that the expression of H19 was associated with distant metastasis in nongastrointestinal tumors (OR = 3.85, 95% CI = 1.31-11.36, P = 0.01) and, in gastrointestinal tumors (OR = 0.34, 95% CI = 0.15-0.78, P = 0.01), lymph node metastasis (OR = 2.04, 95% CI = 1.19-3.48, P = 0.009). Moreover, in gastric cancer, H19 expression was significantly related to histological grade (OR = 0.50, 95% CI = 0.29-0.86, P = 0.01), TNM stage (OR = 0.19, 95% CI = 0.11-0.33, P < 0.01), and tumor invasion depth (OR = 0.11, 95% CI = 0.04-0.27, P < 0.01). Therefore, H19 could serve as a potential marker for progression and metastasis evaluation of cancers. PMID- 27672657 TI - 18S Ribosomal RNA Evaluation as Preanalytical Quality Control for Animal DNA. AB - The 18S ribosomal RNA (rRNA) gene is present in all eukaryotic cells. In this study, we evaluated the use of this gene to verify the presence of PCR amplifiable host (animal) DNA as an indicator of sufficient sample quality for quantitative real-time PCR (qPCR) analysis. We compared (i) samples from various animal species, tissues, and sample types, including swabs; (ii) multiple DNA extraction methods; and (iii) both fresh and formalin-fixed paraffin-embedded (FFPE) samples. Results showed that 18S ribosomal RNA gene amplification was possible from all tissue samples evaluated, including avian, reptile, and FFPE samples and most swab samples. A single swine rectal swab, which showed sufficient DNA quantity and the demonstrated lack of PCR inhibitors, nonetheless was negative by 18S qPCR. Such a sample specifically illustrates the improvement of determination of sample integrity afforded by inclusion of 18S rRNA gene qPCR analysis in addition to spectrophotometric analysis and the use of internal controls for PCR inhibition. Other possible applications for the described 18S rRNA qPCR are preselection of optimal tissue specimens for studies or preliminary screening of archived samples prior to acceptance for biobanking projects. PMID- 27672658 TI - Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules. AB - Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-beta1, PDGF-AB, IL-1beta, and TNF-alpha. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF beta1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic. PMID- 27672659 TI - Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain. AB - Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31.6 mg/kg). UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100) in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D2, GABAA, and opioids, but not by 5-HT1A, receptors. PMID- 27672661 TI - The Evaluation of the Clinical, Laboratory, and Radiological Findings of 16 Cases of Brucellar Spondylitis. AB - Objective. To evaluate the clinical, laboratory, and radiological presentation of 16 cases of brucellar spondylitis. Methods. The clinical manifestations, laboratory tests, and imaging findings of 16 patients (aged from 24 to 66 years) with brucellar spondylitis treated between September 2012 and September 2014 at the Second Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China) were retrospectively analyzed. Results. Clinical manifestations included high fever, severe pain, sweating, and fatigue. One patient had epididymitis, and two showed clear signs of spinal nerve damage. Laboratory tests showed elevated erythrocyte sedimentation rate (ESR) and C-reactive protein content. Serum brucella agglutination tests were positive, and 11 brucella blood cultures were positive. Imaging manifestations mainly consisted of abnormal signals in the intervertebral space or abnormal signals in the adjacent vertebral bodies (16/16, 100%) in magnetic resonance imaging (MRI), disc space narrowing (14/16, 88%) in X-ray and MRI, or bone destruction and sclerosis around the damaged zone (13/16, 81%) in computed tomography, with rare cases of psoas abscess (2/16, 13%) and sequestrum (1/16, 6%). Conclusion. Since brucellar spondylitis exhibited characteristic clinical and imaging manifestations, it could be diagnosed with specific laboratory tests. Early MRI examination of suspected cases could improve rapid diagnosis. PMID- 27672660 TI - Functions of thga1 Gene in Trichoderma harzianum Based on Transcriptome Analysis. AB - Trichoderma spp. are important biocontrol filamentous fungi, which are widely used for their adaptability, broad antimicrobial spectrum, and various antagonistic mechanisms. In our previous studies, we cloned thga1 gene encoding GalphaI protein from Trichoderma harzianum Th-33. Its knockout mutant showed that the growth rate, conidial yield, cAMP level, antagonistic action, and hydrophobicity decreased. Therefore, Illumina RNA-seq technology (RNA-seq) was used to determine transcriptomic differences between the wild-type strain and thga1 mutant. A total of 888 genes were identified as differentially expressed genes (DEGs), including 427 upregulated and 461 downregulated genes. All DEGs were assigned to KEGG pathway databases, and 318 genes were annotated in 184 individual pathways. KEGG analysis revealed that these unigenes were significantly enriched in metabolism and degradation pathways. GO analysis suggested that the majority of DEGs were associated with catalytic activities and metabolism processes that encode carbohydrate-active enzymes, secondary metabolites, secreted proteins, or transcription factors. According to the functional annotation of these DEGs by KOG, the most abundant group was "secondary metabolite biosynthesis, transport, and catabolism." Further studies for functional characterization of candidate genes and pathways reported in this paper are necessary to further define the G protein signaling system in T. harzianum. PMID- 27672662 TI - Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy. AB - Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs). Methods. Fourteen IgA nephropathy (IgAN) patients with chronic tonsillitis (CT) and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz) for 0 (as the control group), 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell activation factor (BAFF) and IgA1, BAFF mRNA expression, and aberrant O glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core beta1,3-galactosyltransferase (C1GALT1) and core beta1,3GalT specific molecular chaperone (Cosmc) were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation. PMID- 27672663 TI - How Effective and Safe Is Bronchial Thermoplasty in "Real Life" Asthmatics Compared to Those Enrolled in Randomized Clinical Trials? AB - There is limited information on the efficacy and safety of bronchial thermoplasty (BT) in real life. We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age: 54.6 +/- 2.9 years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of 3.96 +/- 1.1 to 4.5 +/- 1.2 and 5.5 +/- 0.6 after 6 and 12 months of treatment; p = 0.0007) and in the ACQ score (from 2.77 +/- 0.8 to 1.83 +/- 1.2 and 1.5 +/- 0.8 after 6 and 12 months; p < 0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period (p < 0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics in real life settings. PMID- 27672664 TI - Novel Tubular Biomarkers Predict Renal Progression in Type 2 Diabetes Mellitus: A Prospective Cohort Study. AB - Background. Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction. Methods. A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of >=25% yearly from baseline. Results. Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of >=25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64 0.79, for UANG of 0.71; 95% CI 0.63-0.79, for UNGAL of 0.64; 95% CI 0.56-0.72, and for UKIM-1 of 0.71; 95% CI 0.63-0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles. Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function. PMID- 27672665 TI - The Rise and the Fall of Betatrophin/ANGPTL8 as an Inducer of beta-Cell Proliferation. AB - Diabetes is a global health problem that is caused by impaired insulin production from pancreatic beta-cells. Efforts to regenerate beta-cells have been advancing rapidly in the past two decades with progress made towards identifying new agents that induce beta-cells regeneration. ANGPTL8, also named betatrophin, has been recently identified as a hormone capable of inducing beta-cells proliferation and increasing beta-cells mass in rodents. Its discovery has been cherished as a breakthrough and a game changer in the field of beta-cells regeneration. Initially, ANGPTL8 has been identified as atypical member of the angiopoietin like protein family as a regulator of triglyceride in plasma through its interaction with ANGPTL3 and its regulation of lipoprotein lipase activity. In this review, we will review literature on the proposed role of ANGPTL8 in beta cells proliferation, the controversy regarding this role, and the emerging data questioning its involvement in beta-cells proliferation. Additionally we will discuss new clinical data that describes its role in diabetes and the putative therapeutic targeting of this protein. PMID- 27672667 TI - CXCL13 Promotes Proliferation of Mesangial Cells by Combination with CXCR5 in SLE. AB - As a CXC subtype member of the chemokine superfamily, CXCL13 is considered to be involved in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). To determine the effect of CXCL13 on SLE and explore the potential mechanisms, we tested serum concentrations of CXCL13 in patients and healthy individuals and found that CXCL13 expression was high in SLE patients especially in LN patients. When we treated human renal mesangial cells (HRMCs) in vitro with recombinant human CXCL13, the cell proliferation was accelerated, which was tested by Cell Counting Kit-8 assay and flow cytometry. Western blot and immunofluorescence assay revealed that CXCL13 would lead to phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). However, the effect was weakened after the silence of CXCR5. The results of our study elaborated that high expression of CXCL13 could be involved in the pathogenesis of LN. PMID- 27672666 TI - Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation. AB - Skin inflammatory responses in individuals with allergic dermatitis may be suppressed by dietary vitamin D through induction and upregulation of the suppressive activity of regulatory T (TReg) cells. Vitamin D may also promote TReg cell tropism to dermal sites. In the current study, we examined the capacity of dietary vitamin D3 to modulate skin inflammation and the numbers and activity of TReg cells in skin and other sites including lungs, spleen, and blood. In female BALB/c mice, dietary vitamin D3 suppressed the effector phase of a biphasic ear swelling response induced by dinitrofluorobenzene in comparison vitamin D3-deficient female BALB/c mice. Vitamin D3 increased the percentage of TReg (CD3+CD4+CD25+Foxp3+) cells in the skin-draining lymph nodes (SDLN). The suppressive activity of TReg cells in the SDLN, mesenteric lymph nodes, spleen, and blood was upregulated by vitamin D3. However, there was no difference in the expression of the naturally occurring TReg cell marker, neuropilin, nor the expression of CCR4 or CCR10 (skin-tropic chemokine receptors) on TReg cells in skin, SDLN, lungs, and airway-draining lymph nodes. These data suggest that dietary vitamin D3 increased the percentages and suppressive activity of TReg cells in the SDLN, which are poised to suppress dermal inflammation. PMID- 27672668 TI - The Generation and Characterization of Recombinant Protein and Antibodies of Clostridium perfringens Beta2 Toxin. AB - Introduction. Clostridium perfringens (C. perfringens) beta2 toxin (CPB2) is an important virulent factor of necrotic enteritis in both animals and humans. However, studies of its pathogenic roles and functional mechanisms have been hampered due to the difficulty of purification and lack of specific antibodies against this toxin. Methods. A recombinant His-tagged C. perfringens beta2 (rCPB2) toxin and monoclonal antibodies (McAbs) against CPB2 were generated and characterized by assays of cytotoxicity, immunoblotting, ELISA, neutralization, and immunofluorescence. Results. A His-tagged rCPB2 with integrity and cytotoxicity of native CPB2 was purified from E. coli expressing system, which exhibited a moderate cytotoxicity on NCM460 human intestinal epithelial cells. The rCPB2 could induce apoptotic cell death rather than necrotic death in part through a pathway involved in caspase-3 signaling. Mechanistically, rCPB2 was able to first bind to cell membrane and dynamically translocate into cytoplasm for its cytotoxic activity. Three McAbs 1E23, 2G7 and 2H7 were characterized to be able to immunologically react with CPB2 and neutralize rCPB2 cytotoxicity on NCM460 cells. Conclusion. These results indicated the rCPB2 and antibodies generated in this study are useful tools for studies of biological functions and pathogenic mechanisms of CPB2 in future, which warrants for further investigations. PMID- 27672670 TI - Data concerning the proteolytic resistance and oxidative stress in LAN5 cells after treatment with BSA hydrogels. AB - Proteolytic resistance is a relevant aspect to be tested in the formulation of new nanoscale biomaterials. The action of proteolytic enzymes is a very fast process occurring in the range of few minutes. Here, we report data concerning the proteolytic resistance of a heat-set BSA hydrogel obtained after 20-hour incubation at 60 degrees C prepared at the pH value of 3.9, pH at which the hydrogel presents the highest elastic character with respect to gel formed at pH 5.9 and 7.4 "Heat-and pH-induced BSA conformational changes, hydrogel formation and application as 3D cell scaffold" (G. Navarra, C. Peres, M. Contardi, P. Picone, P.L. San Biagio, M. Di Carlo, D. Giacomazza, V. Militello, 2016) [1]. We show that the BSA hydrogel produced by heating treatment is protected by the action of proteinase K enzyme. Moreover, we show that LAN5 cells cultured in presence of BSA hydrogels formed at pH 3.9, 5.9 and 7.4 did not exhibit any oxidative stress, one of the first and crucial events causing cell death "Are oxidative stress and mitochondrial dysfunction the key players in the neurodegenerative diseases?" (M. Di Carlo, D. Giacomazza, P. Picone, D. Nuzzo, P.L. San Biagio, 2012) [2] "Effect of zinc oxide nanomaterials induced oxidative stress on the p53 pathway" (M.I. Setyawati, C.Y. Tay, D.T. Leaong, 2013) [3]. PMID- 27672669 TI - The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review. AB - As secondary complications remain a significant cause of morbidity and mortality amongst hospitalised trauma patients, the need to develop novel approaches by which to identify patients at risk of adverse outcome is becoming increasingly important. Centred on the idea that patients who experience "poor" outcome post trauma elicit a response to injury that is distinct from those who experience "good" outcome, tailored therapeutics is an emerging concept aimed at improving current treatment regimens by promoting patient-specific therapies. Making use of recent advancements in the fields of genomics, proteomics and metabolomics, numerous groups have undertaken a systems-based approach to analysing the acute immune and inflammatory response to major traumatic and thermal injury in an attempt to uncover a single or combination of biomarkers that can identify patients at risk of adverse outcome. Early results are encouraging, with all three approaches capable of discriminating patients with "good" outcome from those who develop nosocomial infections, sepsis and multiple organ failure, with differences apparent in blood samples acquired as early as 2 h post injury. In particular, genomic data is proving to be highly informative, identifying patients at risk of "poor" outcome with a higher degree of sensitivity and specificity than statistical models built upon data obtained from existing anatomical and physiological scoring systems. Here, focussing predominantly upon human-based research, we provide an overview of the findings of studies that have investigated the immune and inflammatory response to major traumatic and thermal injury at the genomic, protein and metabolite level, and consider both the diagnostic and prognostic potential of these approaches. PMID- 27672671 TI - Dataset on gene expression profiling of multiple murine hair follicle populations. AB - The murine hair follicle contains several different keratinocyte progenitor populations within its compartments. By using antibodies against CD34, Itgalpha6, Sca-1 and Plet-1, we have isolated eight populations and compared their Krt10 and Krt14 expressions using fluorescence microscopy. This improved panel was used in our associated article doi:10.1016/j.scr.2016.06.002 (A.P. Gunnarsson, R. Christensen, J. Li, U.B. Jensen, 2016) [1] and the present dataset describes the basic controls for the FACS. We also used imaging flow cytometry to visualize the identified populations as control. A more detailed analysis of the global gene expression profiling is presented, focusing on the pilosebaceous unit. Murine whole-mounts were stained for heat shock protein Hspa2, which is exclusively expressed by keratinocytes with low or no expression of the four selection markers (IRK). Whole-mount labeling was also conducted to visualize Krt79 and Plet-1 coexpression within the hair follicle and quantification on the distribution of Krt79 positive keratinocytes is presented. PMID- 27672672 TI - Data for chitin binding activity of Moringa seed resistant protein (MSRP). AB - Chitin binding activity of moringa seed resistant protein (MSRP) isolated from defatted moringa seed flour was investigated in the present study "Characterization of soluble dietary fiber from Moringa oleifera seeds and its immunomodulatory effects" (S. Anudeep, V.K. Prasanna, S.M. Adya, C. Radha, 2016) [1]. The assay reaction mixture contained 0.4 mg/ml of MSRP and different amounts (20-100 mg) of chitin. MSRP exhibited binding activity over wide range of chitin concentration. Maximum binding activity was observed at 80 mg of chitin. The property of MSRP to bind chitin can be exploited for its purification. PMID- 27672673 TI - Data on galvanic-evoked head movements in healthy and unilaterally labyrinthectomized rats. AB - In this dataset, we analyzed galvanic-evoked head movements (GEHMs) in the spatial planes of yaw, and roll in normal and unilaterally labyrinthectomized (UL) Wistar rats. The rats were assigned in 4 groups of 10: control, sham, right UL and left-UL. Bilateral galvanic vestibular stimulation (GVS) was presented by our "ring-shaped electrode" design (see "Short-term galvanic vestibular stimulation promotes functional recovery and neurogenesis in unilaterally labyrinthectomized rats" (M. Shaabani et al., 2016) [1]). Required data were collected through video recording of GEHMs followed by image processing and statistical analysis. PMID- 27672674 TI - Data set for phylogenetic tree and RAMPAGE Ramachandran plot analysis of SODs in Gossypium raimondii and G. arboreum. AB - The data presented in this paper is supporting the research article "Genome-Wide Analysis of Superoxide Dismutase Gene Family in Gossypium raimondii and G. arboreum" [1]. In this data article, we present phylogenetic tree showing dichotomy with two different clusters of SODs inferred by the Bayesian method of MrBayes (version 3.2.4), "Bayesian phylogenetic inference under mixed models" [2], Ramachandran plots of G. raimondii and G. arboreum SODs, the protein sequence used to generate 3D sructure of proteins and the template accession via SWISS-MODEL server, "SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information." [3] and motif sequences of SODs identified by InterProScan (version 4.8) with the Pfam database, "Pfam: the protein families database" [4]. PMID- 27672675 TI - Dataset generated using hyperplexing and click chemistry to monitor temporal dynamics of newly synthesized macrophage secretome post infection by mycobacterial strains. AB - Here we provide data for SILAC and iTRAQ based hyperplexing combined with BONCAT based click chemistry for selective enrichment of newly synthesized proteins secreted by THP1 macrophages at various time points after infection with four different strains of Mycobacterium tuberculosis. The macrophages were infected with H37Ra, H37Rv, BND433 and JAL2287 strains of M. tuberculosis. Newly synthesized secreted host proteins were observed, starting from six hours post infection till 26 h, at 4 h intervals. We have combined BONCAT with hyperplexing (18-plex), which blends SILAC and iTRAQ, for the first time. Two sets of triplex SILAC were used to encode the strains of M. tuberculosis - H37Ra & H37Rv in one and BND433 & JAL2287 in another with a control in each. BONCAT was used to enrich the secretome for newly synthesized proteins while 6-plex iTRAQ labeling was employed to quantify the temporal changes in the captured proteome. Each set of 18-plex was run in 4 MS replicates with two linear and two non-linear separation modes. This new variant of hyperplexing method, combining triplex SILAC with 6 plex iTRAQ, achieves 18-plex quantitation in a single MS run. Hyperplexing enables large scale spatio-temporal systems biology studies where large number of samples can be processed simultaneously and in quantitative manner. Data are available via ProteomeXchange with identifier ProteomeXchange: PXD004281. PMID- 27672676 TI - Metastatic papillary serous uterine cancer presenting as a rash. AB - BACKGROUND: We report diagnosis and management of stage IV papillary serous uterine cancer with initial clinical presentation as a skin rash. CASE: A 62-year old postmenopausal female developed an erythematous rash beginning on her right lower abdomen and progressively spreading to her left abdomen, vulva, and neck. After a trial of antibiotic treatment, biopsy of left neck and right thigh skin nodules revealed papillary serous carcinoma. Abdominopelvic tomography revealed endometrial thickening and a 5 cm left adnexal mass. Subsequent endometrial biopsy also revealed papillary serous carcinoma, with pathology similar to that of the skin lesions. She received 6 cycles of carboplatin and paclitaxel chemotherapy with improvement of her skin lesions and overall performance status. However, her CA-125 level continued to rise and she was treated with single-agent carboplatin with progression of both her internal and cutaneous disease. She was transitioned to hospice with palliative radiation and died 2 months after discontinuing chemotherapy, 10 months after presentation. CONCLUSION: Cutaneous metastasis is a rare presentation of metastatic uterine cancer. Treatment with chemotherapy may result in a positive response and should be considered. PMID- 27672677 TI - Left paraaortic, inframesenteric lymphadenectomy preserving the superior hypogastric plexus supported by indocyanine green (ICG) labeling of the lymphatic compartment in cervical cancer. AB - Superior hypogastric plexus (SHG) contains mainly sympathetic and most probably also postganglionic parasympathetic fibers. Thus, surgical damage of SHG may cause autonomic pelvic organ dysfunction (Kraima et al., 2015). As already shown for rectal cancer, preservation of the autonomic nerves is facilitated by robotic surgery and may avoid sexual dysfunctions and voiding disorders (Kim et al., 2015). In this educational video, we demonstrate left lower paraaortic lymph node dissection preserving the SHG using ICG fluorescence to label the lymphatic compartment. Prior to total mesometrial resection (TMMR) with therapeutic lymphadenectomy for cervical cancer (Hockel et al., 2009, Kimmig et al., 2013) 4 * 0.5 ml of a 1.66 mg/ml Indocyanine green solution (ICG Pulsion(r), PMS SE, Feldkirchen, Germany) was injected into the uterine cervix at all four quadrants, 0.5 cm in depth (Kimmig et al., 2016). The lymphatic network of the downstream common iliac and inferior paraaortic lymph compartments of the uterine cervix is visualized (ICG fluorescence) including the individual connecting vessels between the different compartments. As can be demonstrated, the medial upper common iliac (subaortic) compartment drains preferentially into the anterior (mesenteric) compartment, whereas lateral common iliac lymphatic vessels mainly drain to the posterior (lumbar) paraaortic compartment. The autonomic nerve fibers of the SHP may easily be identified and preserved due to the excellent image resolution and the discrimination from fluorescent lymphatic structures. The video shows the preparation of left lower paraaortic nodes in cervical cancer following ICG labeling using a da Vinci Xi system(r). This technique seems not only advantageous for preserving SHP, but even more highly educational to learn surgical anatomy for trainees. PMID- 27672679 TI - Hemostatic Nanoparticles Improve Survival Following Blunt Trauma Even after 1 Week Incubation at 50 degrees C. AB - According to the CDC, the leading cause of death for both men and women between the ages of 5 and 44 is traumatic injury. Blood loss is the primary cause of death at acute time points post trauma. Early intervention is critical to save lives, and yet there are no treatments to stop internal bleeding that can be deployed in the field. In this work, we developed hemostatic nanoparticles that are stable at high temperatures (50 degrees C for 7 days) and are still effective at stopping bleeding and improving survival over the one hour time period in a rat liver injury model. These particles are exceptionally simple: PLA based nanospheres functionalized with PEG terminated with variants of the RGD motif. This simple system can be stored at temperatures up to 50 degrees C and maintain size, shape, and efficacy. The particles lead to a reduction in bleeding and increased acute survival with significance compared to both control particles and saline. Overall, these hemostatic nanoparticles offer an important step towards an immediate intervention in the field to stop bleeding and improve survival. PMID- 27672680 TI - A Molecular Take on Malignant Rhabdoid Tumors. AB - The molecular basis for the clinical heterogeneity observed in patients with malignant rhabdoid tumors is unknown. Recently, two reports revealed molecular inter-tumor heterogeneity in teratoid/rhabdoid tumors (ATRTs) and extra-cranial MRTs (ecMRTs) using genomic, transcriptomic and epigenomic profiling. Distinct molecular subgroups were identified and new therapeutic targets were revealed. PMID- 27672678 TI - Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross Sectional Study. AB - Introduction. The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA). Methods. Ten male SpA patients (mean +/- SD age 39 +/- 4.1 years) were compared with ten healthy controls matched for sex, age, body mass index, and self reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken from m. vastus lateralis. Results. SpA patients presented with significantly lower appendicular lean body mass (LBM) (p = 0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients (p = 0.03) with a parallel trend for specific strength (p = 0.08). Biopsy samples from the SpA patients revealed significantly smaller cross sectional area (CSA) of type II muscle fibers (p = 0.04), but no difference in CSA type I fibers. Conclusions. Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA. PMID- 27672681 TI - The potent, indirect adenosine monophosphate- activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice. AB - There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K) / mechanistic target of rapamycin (mTOR) signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate activated protein kinase (AMPK) can inhibit signaling in both of these pathways and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date. We tested whether R419 activates AMPK in dorsal root ganglion (DRG) neurons and if this leads to decreased pain hypersensitivity in mice. We find that R419 activates AMPK in DRG neurons resulting in decreased MAPK signaling, decreased nascent protein synthesis and enhanced P body formation. R419 attenuates nerve growth factor-(NGF) induced changes in excitability in DRG neurons and blocks NGF induced mechanical pain amplification in vivo. Moreover, locally applied R419 attenuates pain hypersensitivity in a model of post-surgical pain and blocks the development of hyperalgesic priming to both NGF and incision. We conclude that R419 is a promising lead candidate compound for the development of potent and specific AMPK activation to inhibit pain hypersensitivity as a result of injury. PMID- 27672682 TI - Single-View Food Portion Estimation Based on Geometric Models. AB - In this paper we present a food portion estimation technique based on a single view food image used for the estimation of the amount of energy (in kilocalories) consumed at a meal. Unlike previous methods we have developed, the new technique is capable of estimating food portion without manual tuning of parameters. Although single-view 3D scene reconstruction is in general an ill-posed problem, the use of geometric models such as the shape of a container can help to partially recover 3D parameters of food items in the scene. Based on the estimated 3D parameters of each food item and a reference object in the scene, the volume of each food item in the image can be determined. The weight of each food can then be estimated using the density of the food item. We were able to achieve an error of less than 6% for energy estimation of an image of a meal assuming accurate segmentation and food classification. PMID- 27672683 TI - Maybe it is all in your head. AB - Recent research provides strong evidence that in some cases of intractable chronic pain, the origin of the pain signal is in the brain--rather than the body. PMID- 27672684 TI - Is an SGLT2 inhibitor right for your patient with type 2 diabetes? AB - Metformin isn't quite doing the job or is contraindicated? Here's a look at the patients who may benefit from these agents and the monitoring required. PMID- 27672685 TI - A new paradigm for pain? AB - A new way of thinking about pain that occurs in the absence of a pathophysiologic process or injury may alter our approach to conditions like fibromyalgia. PMID- 27672686 TI - Bone disease in patients with kidney disease: A tricky interplay. AB - Managing bone disease in patients with kidney disease involves frequent lab testing and careful evaluation of therapeutic options. This review provides guidance. PMID- 27672687 TI - Practice Alert: Need-to-know information for the 2016-2017 flu season. AB - ACIP now advises against using the LAIV nasal spray. In addition, 2 new vaccines are available and 2 more may soon be approved. PMID- 27672688 TI - Depigmented patches, mild scaling on newborn . Dx? AB - Depigmented patches covering approximately 15% of newborn's body, surrounded by areas of thickened skin. Mild scaling and hyperpigmentation. PMID- 27672690 TI - Pruritic, lightly-scaled patches on wrists. AB - A rash first appeared on this patient's left wrist and then spread to his right. Was his chrome-colored watch to blame--or was there a different cause? PMID- 27672691 TI - Which SSRIs most effectively treat depression in adolescents? AB - We don't know which selective serotonin reuptake inhibitors (SSRIs) are the most effective and safe because no studies have compared these antidepressants with each other. Three SSRI antidepressant medications--fluoxetine, sertraline, and escitalopram--produce modest improvements (about 5% to 10%) in standardized depression scores without a significant increase in the risk of suicide-related outcomes (suicidal behavior or ideation) in adolescent patients with major depression of moderate severity. PMID- 27672689 TI - PURLs: Yeast infection in pregnancy? Think twice about fluconazole. AB - This study's findings regarding the risk of miscarriage may mean it's time to forego fluconazole in favor of topical azoles as first-line treatment. PMID- 27672692 TI - Do autologous blood and PRP injections effectively treat tennis elbow? AB - Both approaches reduce pain, but the improvement with platelet-rich plasma (PRP) is not clinically meaningful. Autologous blood injections (ABIs) are more effective than corticosteroid injections for reducing pain and disability in patients with tennis elbow in both the short and long term. PMID- 27672694 TI - Vitamin and Mineral Intake Is Inadequate for Most Americans: What Should We Advise Patients About Supplements? AB - This supplement examines the role of vitamin and mineral supplements in increasing nutrient intake and reducing nutrient deficiencies and inadequacies. Although research is needed to study the effects of dietary supplements on chronic disease outcomes, US health care providers need to know how to advise their patients about adding vitamins and minerals to their diets. PMID- 27672693 TI - Pruritus since childhood. AB - The itchy rash had been previously diagnosed as psoriasis. But treatment provided minimal relief. So what was causing the itch? PMID- 27672695 TI - Catalyst-Free sp3 C-H Acyloxylation: Regioselective Synthesis of 1-Acyloxy Derivatives of the Natural Product Tanshinone IIA. AB - Tanshinone IIA is a valuable bioactive natural product isolated from the well known Chinese herb Danshen. Structural manipulation of the A-ring of tanshinone IIA is rather limited. In this study, a substrate tautomerization-induced catalyst-free benzylic sp3 C-H acyloxylation approach is reported that allows the direct introduction of various acyloxy groups at the A-ring benzylic methylene of various tanshinone IIA substrates, thus avoiding the use of expensive transition metal catalysts and the production of harmful byproducts. This approach features a unique acid-induced reversible enolization/oxa-conjugate addition process followed by oxidation to exclusively give a series of diverse 1-acyloxylated derivatives under simple conditions in a regioselective manner. Compared with the literature procedures, this protocol demonstrates a higher efficiency, a more robust functional-group tolerance, atom economy, and lower cost. PMID- 27672696 TI - Synthesis of Birnessite in the Presence of Phosphate, Silicate, or Sulfate. AB - Layered manganese (Mn) oxides, such as birnessite, are versatile materials in industrial applications and common minerals mediating elemental cycling in natural environment. Many of birnessite properties are controlled by Mn(III) concentration and particle sizes. Thus, it is important to synthesize birnessite nanoparticles with controlled Mn(III) concentrations and sizes so that one can tune its properties for many applications. Birnessite was synthesized in the presence of oxyanions (phosphate, silicate, or sulfate) during reductive precipitation of KMnO4 by HCl and characterized using multiple synchrotron X-ray techniques, electron microscopy, and diffuse reflectance UV-vis spectroscopy. Results indicate that all three anions decrease MnO6 sheet sizes, attributed to oxyanion adsorption on edges of the sheets, inhibiting their lateral growth. As a result of decreased sizes, sheets undergo significant structural contraction. Meanwhile, Mn(III) concentration significantly increases with increasing oxyanion/Mn ratio. The increased Mn(III) concentration, along with the decreased size, enlarges both direct and indirect band gaps of birnessite. Phosphate imposes the strongest influence, followed by silicate and then by sulfate, consistent with their decreasing adsorption affinity. Reacting with 1 M KOH solution effectively removed the adsorbed oxyanions while leading to increased sheet sizes, probably due to oriented attachment-driven particle growth mechanisms. The results have important implications for developing highly performed birnessite materials, for example, small size Mn(III)-rich birnessite for photochemical and catalytic applications, as well as for understanding chemical compositional variations of naturally occurring birnessite. PMID- 27672697 TI - Chemical Synthesis of Peptides Containing Site-Specific Advanced Glycation Endproducts. AB - In nature, proteins, lipids, and nucleic acids can nonenzymatically react with sugars and sugar degradation products to give rise to a diverse range of modifications, known as advanced glycation endproducts (AGEs). These AGEs typically occur at lysine and arginine residues of long-lived proteins, such as collagen, and can modify the structure and function of the native protein. AGEs accumulate during the normal aging process, and AGE formation is dramatically accelerated with diabetes. AGEs have also been implicated in a wide range of debilitating conditions including cardiovascular, renal failure, and neurodegenerative diseases. Thus, there is an ongoing interest in studying the role of AGEs in different aspects of these disorders. Typically, glycated proteins are prepared using nonspecific in vitro incubation techniques. However, this method results in a complex mixture of products which is then employed without further purification. In order to determine the effect of individual AGEs in a peptide sequence, in this Account, we highlight our synthetic methods for site-specifically introducing five frequently occurring AGEs, namely, Nepsilon (carboxymethyl)lysine (CML), Nepsilon-(carboxyethyl)lysine (CEL), pyrraline, glyoxal-lysine dimer (GOLD), and methylglyoxal-lysine dimer (MOLD) into collagen peptides. Both a collagen model peptide (CMP) and the telopeptide region of human type I alpha1 collagen (CTP) were chosen due to being prone to glycation and cross-linking in vivo. For the preparation of the AGE-modified collagen peptides, we investigated both the initial preparation of AGE building blocks in solution followed by incorporation into Fmoc-SPPS, as well as an on-resin method whereby AGEs were selectively introduced by modification of the side-chain of an unprotected resin-bound lysine. Both of our synthetic methods enabled the site specifically modified AGE-containing collagen peptides to be obtained in high purity and yield. In addition, the on-resin method had the added advantage of requiring fewer synthetic steps. We then evaluated the impact of the specific AGEs on the properties of the native protein and found that the AGE modifications protected against proteolytic digestion, enhanced copper binding at physiological pH, and, for the cross-linking AGEs, disrupted the triple helical structure of CMPs. Overall these synthetic methods offered a new strategy for preparing peptides site-specifically modified by AGEs, which can be applied to other peptidic systems, thereby enabling further insights into the biochemical consequences of AGEs. PMID- 27672698 TI - A Bifunctional Europium-Organic Framework with Chemical Fixation of CO2 and Luminescent Detection of Al3. AB - A novel three-dimensional lanthanide-organic framework {[Eu(BTB)(phen)].4.5DMF.2H2O}n (1) has been synthesized. Structural characterization suggests that framework 1 possesses one-dimensional channels with potential pore volume, and the large channels in the framework can capture CO2. Interestingly, investigations on the cycloaddition reaction of CO2 and epoxides reveal that compound 1 can be considered as an efficient catalyst for CO2 fixation with epoxides under 1 atm pressure. Importantly, 1 can be reused at least five times without any obvious loss in catalytic activity. Furthermore, the luminescent explorations of 1 reveal that 1 can act as a recyclable sensor of Al3+, and the corresponding detection limit can reach 5 * 10-8 M (1.35 ppb), which is obviously lower than the United States Environmental Protection Agency's recommended level of Al3+ in drinking water (200 ppb). These results show that 1 has a level of sensitivity higher than that of other reported MOF-based sensors of Al3+. PMID- 27672699 TI - Mn-N-C Nanoreactor Prepared through Heating Metalloporphyrin Supported in Mesoporous Hollow Silica Spheres. AB - Mesoporous hollow silica spheres have been drawing tremendous interest due to their special structure and properties and potential applications. Here we synthesized a nanoreactor via ship-in-bottle method, encapsulated with Mn-N-C by heating manganese porphyrin in nanocages of mesoporous hollow silica spheres. And manganese porphyrin is first encapsulated and confined in the hollow spheres. The nanoreactors are investigated through transmission electron microscopy (TEM) and high angle annular dark field scanning TEM (HAADF-STEM) as well as nitrogen adsorption-desorption isotherms. The results demonstrate that the mesoporous hollow spheres with well-defined morphology hold large pore volumes (0.29-0.46 cm3 g-1), high specific surface areas (428-600 m2 g-1) and uniform pore sizes (4.0 nm). In addition, the ethylbenzene oxidation is conducted in order to explore the catalytic performance of the nanoreactors. And the nanoreactors are observed to possess remarkable catalytic activity and attractive stability for ethylbenzene oxidation, which should be ascribed to the special architectures and confined effect. PMID- 27672700 TI - Immobilizing Tetraphenylethylene into Fused Metallacycles: Shape Effects on Fluorescence Emission. AB - Herein, we describe the selective formation of a discrete fused metallarhomboid and a triangle by the careful control of the shape and stoichiometry of the building blocks. A tetraphenylethylene (TPE)-based tetrapyridyl donor is exploited as the bridging component, and coordination immobilization of the TPE unit within the rigid metallacyclic frameworks efficiently suppresses its intramolecular rotational motions. As a result, the fused polygons are innately emissive in dilute solution, representing an alternative to aggregation-induced emission. Upon further molecular aggregation, these metallacycles display aggregation-induced enhanced emissions. Interestingly, the fused rhomboid 7 shows a weaker fluorescence in dilute solutions relative to that of the fused triangle 8, while a reversal of emission intensities was observed in the aggregated state. These markedly different fluorescence efficiencies are likely due to the differences in the shapes of the fused polygons. Thus, this work shows that the properties of supramolecular coordination complexes can be affected by subtle structural factors, which can be controlled easily and precisely at the molecular level. PMID- 27672701 TI - Exploring the Different Roles of Particle Size in Photoelectrochemical and Photocatalytic Water Oxidation on BiVO4. AB - Water oxidation on visible-light-active bismuth vanadate (BiVO4) has commonly been demonstrated to be viable in powder suspension (PS) and particulate photoelectrochemical (PEC) systems. Here, we demonstrate that particle size reduction, which is known to be efficacious in promoting charge carrier extraction and boosting surface active sites, has an opposite effect on BiVO4's photoactivity in the two systems. With three BiVO4 samples of distinctive particle sizes, smaller BiVO4 particle size is shown to be beneficial for enhancing PEC photocurrent generation, but deleterious for photocatalytic O2 evolution on suspended BiVO4. Such contrary effect of particle size in the PEC and PS systems is revealed to be due to the different governing factors of the systems: charge transport in the former and charge separation in the latter. Smaller particle size was found to enrich the interparticle and the particle/FTO substrate contacts which improve charge transport and charge collection efficiency in BiVO4 particulate electrode. On the contrary, larger particle size is necessary for improved photocatalytic O2 evolution because of increased crystallinity and greater band bending, which are essential for charge separation. PMID- 27672702 TI - Direct Combinatorial Pathway Optimization. AB - Combinatorial engineering approaches are becoming increasingly popular, yet they are hindered by the lack of specialized techniques for both efficient introduction of sequence variability and assembly of numerous DNA parts, required for the construction of lengthy multigene pathways. In this contribution, we introduce a new combinatorial multigene pathway assembly scheme based on Single Strand Assembly (SSA) methods and Golden Gate Assembly, exploiting the strengths of both assembly techniques. With a minimum of intermediary steps and an accompanying set of well-characterized and ready-to-use genetic parts, the developed workflow allows effective introduction of various libraries and efficient assembly of multigene pathways. It was put to the test by optimizing the lycopene pathway as proof-of-principle. The here constructed libraries yield ample variation in lycopene production. In addition, good-performing transformants with a significantly higher lycopene production were obtained as compared to previously published reference strains. The best selected producer yielded 3-fold improvement in lycopene titers up to 448 mg lycopene/g CDW. The proposed workflow in combination with the accompanying sets of ready-to-use expression and carrier plasmids, will allow the combinatorial assembly of increasingly lengthy product pathways with minimal effort. PMID- 27672703 TI - Increasing the Impact of Materials in and beyond Bio-Nano Science. AB - This is an exciting time for the field of bio-nano science: enormous progress has been made in recent years, especially in academic research, and materials developed and studied in this area are poised to make a substantial impact in real-world applications. Herein, we discuss ways to leverage the strengths of the field, current limitations, and valuable lessons learned from neighboring fields that can be adopted to accelerate scientific discovery and translational research in bio-nano science. We identify and discuss five interconnected topics: (i) the advantages of cumulative research; (ii) the necessity of aligning projects with research priorities; (iii) the value of transparent science; (iv) the opportunities presented by "dark data"; and (v) the importance of establishing bio-nano standards. PMID- 27672705 TI - Electrically Tunable Multiterminal SQUID-on-Tip. AB - We present a new nanoscale superconducting quantum interference device (SQUID) whose interference pattern can be shifted electrically in situ. The device consists of a nanoscale four-terminal-four-junction SQUID fabricated at the apex of a sharp pipet using a self-aligned three-step deposition of Pb. In contrast to conventional two-terminal-two-junction SQUIDs that display optimal sensitivity when flux biased to about a quarter of the flux quantum, the additional terminals and junctions allow optimal sensitivity at arbitrary applied flux, thus eliminating the magnetic field "blind spots". We demonstrate spin sensitivity of 5 to 8 MUB/Hz1/2 over a continuous field range of 0 to 0.5 T with promising applications for nanoscale scanning magnetic imaging. PMID- 27672706 TI - Identification, Tissue Distribution, and Bioaccumulation Potential of Cyclic Perfluorinated Sulfonic Acids Isomers in an Airport Impacted Ecosystem. AB - The use of cyclic perfluoroalkyl acids as anticorrosive agents in hydraulic fluids remains a poorly characterized source of organofluorine compounds to the environment. Here, we investigated the presence of perfluoroethylenecyclohexanesulfonate (PFECHS) isomers in environmental samples for the first time using a combination of high resolution and tandem mass spectrometry. Five distinct peaks attributed to different isomers of PFECHS and perfluoropropylcyclopentanesulfonate (PFPCPeS) were identified in environmental samples. The sum of PFECHS and PFPCPeS isomers displayed logarithmically decreasing spatial trends in water (1.04-324 ng/L) and sediment samples (=240 mg/dL (13.3 mmol/L) than days when it was not enabled (P < 0.001 for each). Users who switched from the MiniMed Paradigm Veo system to the MiniMed 640G system had fewer excursions below <=70 mg/dL (P < 0.001) and >=240 mg/dL (P < 0.001). SG values following automatically resumed pump suspension events recovered more rapidly and had a more stabilized endpoint than following manually resumed events. CONCLUSIONS: Automated insulin management features of the MiniMed 640G system can reduce the frequency of both high and low SG values and help stabilize SG after resumption of insulin delivery. PMID- 27672713 TI - Abstracts for 15th World Congress on Menopause. PMID- 27672711 TI - Just Keep Swimming: Neuroendocrine, Metabolic, and Behavioral Changes After a Forced Swimming Test in Zebrafish. AB - In this study, we show that an adaptation of the spinning test can be used as a model to study the exercise-exhaustion-recovery paradigm in fish. This forced swimming test promotes a wide range of changes in the hypothalamus-pituitary interrenal axis functioning, intermediary metabolism, as well in fish behavior at both exercise and recovery periods. Our results pointed that this adapted spinning test can be considered a valuable tool for evaluating drugs and contaminant effects on exercised fish. This can be a suitable protocol both to environmental-to evaluate contaminants that act in fish energy mobilization and recovery after stressors-and translational perspectives-effects of drugs on exercised or stressed humans. PMID- 27672714 TI - Relationship between vitamin D receptor gene polymorphisms, cardiovascular risk factors and adiponectin in a healthy young population. AB - AIM: To explore the association between VDR polymorphisms and several cardiovascular risk factors and adiponectin. MATERIALS & METHODS: Three-hundred and sixty-nine healthy students were randomly selected. Five VDR polymorphisms were genotyped: BsmI rs1544410; Cdx2 rs11568820; ApaI rs7975232; TaqI rs731236 and FokI rs2228570. BMI, waist circumference (WC), blood pressure, lipid/glycemic profiles and adiponectin were assessed. RESULTS: In men, BsmI, ApaI and TaqI were associated with BMI and WC (p < 0.05). FokI was associated with triglycerides and high-density lipoprotein levels (p = 0.0036; p = 0.005) whereas BsmI and Cdx2 were associated with adiponectin levels (p = 0.026; p = 0.048). Associations disappeared after BMI and WC adjustments. In women, ApaI was associated with systolic blood pressure (p = 0.02). CONCLUSION: Our study demonstrated a gender specific difference between VDR SNPs and various cardiovascular risk factors and adiponectin. PMID- 27672715 TI - Rh(II)-Catalyzed Transannulation of N-Sulfonyl-1,2,3-Triazoles with 2,1 Benzisoxazoles or 1,2-Benzisoxazoles. AB - A Rh(II)-catalyzed transannulation of N-sulfonyl-1,2,3-triazoles with 2,1 benzisoxazoles has been developed, which affords an efficient method for the synthesis of quinazoline derivatives. The transformation represents an unprecedented example which utilizes N-sulfonyl-1,2,3-triazole as an aza-[2C] component in cycloadditions. Meanwhile, a Rh(II)-catalyzed formal [3 + 2] cycloaddition of N-sulfonyl-1,2,3-triazoles with 1,2-benzisoxazoles is also presented, which enables the rapid synthesis of functionalized imidazole derivatives. PMID- 27672716 TI - One stage placement of permanent implant compared to two stage tissue expander reconstruction. AB - With the advent of the skin sparing mastectomy, immediate breast reconstruction with placement of the definitive prosthesis at the time of mastectomy is possible. The question remains: does single-stage prosthetic reconstruction result in greater numbers of complications or rates of re-operation, compared to two-stage tissue expander reconstruction? A retrospective cohort study of a single centre?s experience with these techniques was carried out. From 2004 to 2012, 54 cases of immediate breast reconstruction with implant were identified, and 108 cases of immediate breast reconstruction using a tissue expander were identified. Gathered preoperative data included tumour, prior exposure to radiation, preoperative chemotherapy, smoking, and comorbidities. Complication rates, as well as the rate of secondary operations, were examined. There were no significant increased risks in the rate of post-operative complications (p = .910, odds ratio = 0.9) nor in the rate of re-operation (p = 0.421, odds ratio = 1.4) associated with the insertion of a definitive prosthesis at the time of skin sparing mastectomy. However, previously radiated breasts experienced a 100% rate of wound complications in our subset of 9 breasts that underwent one stage breast reconstruction with immediate final prosthesis placement. Our study suggests that patients with early stage disease can undergo single stage breast reconstruction without increased risk of complications nor need for secondary operations. While the mean time to completion of the reconstructive process is shortened by 5 months with the single stage technique, implant based breast reconstruction requires careful counseling and patient selection in radiated patients. PMID- 27672718 TI - Ellipsometric Study of Monodisperse Silica Particles at an Oil-Water Interface. AB - Results are reported for ellipsometric measurements of hydrophobized monodisperse silica particles, with a diameter of about 25 nm, spread at the toluene-water interface. Theoretical values for the ellipsometric parameters are derived by treating the particles as a core-shell model and performing integrations of the refractive index profile through the interface using Drude's equations. With justifiable choices of the fixed parameters for the system, the agreement is good between measured and calculated values for the ellipsometric parameter Delta as a function of the amount of silica particles added to the interface. However, the results at high particle concentration at the interface are consistent either with coverage greater than a close-packed monolayer or with a monolayer with corrugations whose amplitude is less than the radius of the particles. The results show that this is not a suitable method for the determination of the contact angle of the particles at the oil-water interface. PMID- 27672717 TI - Epigenome-wide differential DNA methylation between HIV-infected and uninfected individuals. AB - Epigenetic control of human immunodeficiency virus-1 (HIV-1) genes is critical for viral integration and latency. However, epigenetic changes in the HIV-1 infected host genome have not been well characterized. Here, we report the first large-scale epigenome-wide association study of DNA methylation for HIV-1 infection. We recruited HIV-infected (n = 261) and uninfected (n = 117) patients from the Veteran Aging Cohort Study (VACS) and all samples were profiled for 485,521 CpG sites in DNA extracted from the blood. After adjusting for cell type and clinical confounders, we identified 20 epigenome-wide significant CpGs for HIV-1 infection. Importantly, 2 CpGs in the promoter of the NLR family, CARD domain containing gene 5 (NLRC5), a key regulator of major histocompatibility complex class I gene expression, showed significantly lower methylation in HIV infected subjects than in uninfected subjects (cg07839457: t = -6.03, Pnominal = 4.96 * 10-9; cg16411857: t = -7.63, Pnominal = 3.07 * 10-13). Hypomethylation of these 2 CpGs was replicated in an independent sample (GSE67705: cg07839457: t = 4.44, Pnominal = 1.61 * 10-5; cg16411857: t = -5.90; P = 1.99 * 10-8). Methylation of these 2 CpGs in NLRC5 was negatively correlated with viral load in the 2 HIV-infected samples (cg07839457: P = 1.8 * 10-4; cg16411857: P = 0.03 in the VACS; and cg07839457: P = 0.04; cg164111857: P = 0.01 in GSE53840). Our findings demonstrate that differential DNA methylation is associated with HIV infection and suggest the involvement of a novel host gene, NLRC5, in HIV pathogenesis. PMID- 27672719 TI - Theory in Highly Cited Studies of Sexual Minority Parent Families: Variations and Implications. AB - This article includes a systematic review and citation analysis of the literature regarding sexual minority parent families, particularly attending to what theories have been used, and how. We consider the importance of theoretical frameworks for future research and implications for policy, practice, and law related to sexual minority parent families. Our review targets 30 highly cited studies located through Google Scholar (as an interdisciplinary search engine) and published within a specific timeframe (2005-2010). We highlight the dominant theoretical models employed across disciplines studying sexual minority parent families. Although the majority of studies reviewed referred to theoretical models or perspectives, explicit theoretical grounding was frequently lacking. Instead, the empirical work reviewed appeared to have a predominantly applied focus in addressing public debates on sexual minority parent families. We provide recommendations for how theory might be more fully integrated into the social science literature on sexual minority parents and their children. PMID- 27672720 TI - Experience of Low-Dose, Short-Course Palliative Radiotherapy for Bleeding from Unresectable Gastric Cancer. AB - BACKGROUND/AIMS: The optimal regimen of radiotherapy (RT) for bleeding from gastric cancer (GC) has not yet been established. The aim of this study was to evaluate the usefulness of low-dose, short-course palliative RT (LSP-RT) for bleeding from GC. MATERIAL AND METHODS: We reviewed the clinical data of 18 patients (26 courses) who received palliative RT for bleeding from GC between 2004 and 2014. The radiation dose was 6 Gy in three fractions. The total courses of RT for each patient were 1-4 (median, 1). RESULTS: The treatment success rate of the first and the additional RT at two weeks after RT was 55% and 75%, respectively. Regarding first RT, there was a statistically significant increase in the mean hemoglobin level for one month (p = 0.009) and a significant decrease in the mean number of transfused red blood cell units for one month (p = 0.012). Toxicities were observed in two patients: one patient who received chemotherapy developed grade 3 afebrile leukocytopenia and another who had a malignant stricture suffered from a gastric obstruction. The performance status was improved in 3 of the 12 evaluable patients (25%) and dietary intake became possible one month after RT in three of the four patients who had not been able to eat before RT. CONCLUSION: LSP-RT is expected to be not only an effective and safe treatment option for bleeding from GC, but also repeatable in cases of rebleeding. Furthermore, this treatment modality may be able to improve the patient's quality of life. PMID- 27672721 TI - Reply to Comment on 'Magnetic bead detection using nano-transformers'. PMID- 27672722 TI - Physiological and functional changes in the stratum corneum restored by oestrogen in an ovariectomized mice model of climacterium. AB - Significant decreases in hormonal levels at menopause induce physiological and functional discomfort in the skin. Representative changes at menopause are based on so-called dry skin. However, there is no evidence to explain the mechanism, even though hydration of the stratum corneum (SC) in women at menopause is comparable with that at premenopause but is enhanced by hormone replacement therapy. This study objective was to evaluate structural and functional changes in the SC in ovariectomized mice model of menopause. Hydration of the SC, recovery of the permeability barrier function, integrity and cohesion of the SC, and irritant dermatitis were analysed in mice that underwent ovariectomy with or without replacement of 17beta-estradiol. In ovariectomized mice, hydration of the SC was reduced, recovery of permeability barrier function after acute disruption was impaired, and integrity of the SC was weakened and was associated with increased cohesion and increased levels of irritant dermatitis. Oestrogen replacement treatment restored all changes. Immunohistochemistry revealed reduced levels of expression of desmoglein-1 and differentiation markers of epidermis in ovariectomized mice compared with control mice and mice with oestrogen replacement treatment. These changes might be directly associated with weakened integrity and impaired permeability barrier function of the SC in ovariectomized mice. This study results reveal that so-called dry skin at menopause is caused by not only lower hydration of the SC but also complicated structural and functional changes in the SC and skin. PMID- 27672723 TI - Infective endocarditis. PMID- 27672724 TI - Designing homes to welcome refugees. PMID- 27672725 TI - Illness as transformative experience. PMID- 27672727 TI - Repetitive transcranial magnetic stimulation for treatment resistant depression: Re-establishing connections. AB - Repetitive transcranial magnetic stimulation (rTMS) is a relatively recent addition to the neurostimulation armamentarium for treating individuals suffering from treatment refractory depression and has demonstrated efficacy in clinical trials. One of the proposed mechanisms of action underlying the therapeutic effects of rTMS for depression involves the modulation of depression-associated dysfunctional activity in distributed brain networks involving frontal cortical and subcortical limbic regions, via changes to aberrant functional and structural connectivity. Although there is currently a paucity of published data, we review changes to functional and structural connectivity following rTMS for depression. Current evidence suggests an rTMS-induced normalisation of depression-associated dysfunction within and between large scale functional networks, including the default mode, central executive and salience networks, associated with an amelioration of depressive symptoms. Additionally, changes to measures of white matter microstructure, primarily in the dorsolateral prefrontal cortex, have also been reported following rTMS for depression, possibly reversing depression associated abnormalities. We argue that measures of functional and structural connectivity can be used to optimise rTMS targeting within the dorsolateral prefrontal cortex and also to explore novel rTMS targets for depression. Finally, we discuss the utility of measures of brain connectivity as predictive biomarkers of rTMS treatment response in guiding therapeutic decisions. PMID- 27672726 TI - Harrison Clark Spencer. PMID- 27672728 TI - Laparoscopic Transcystic Common Bile Duct Exploration in the Elderly is as Effective and Safe as in Younger Patients. AB - BACKGROUND: Choledocholithiasis represents a greater proportion of gallstone in the elderly. Elderly patients have more comorbidity, which could increase the operative risk and postoperative complications. However, no study has focused on the effect and safety of laparoscopic transcystic common bile duct exploration (LTCBDE) in elderly patients. The aim of this study was to investigate whether LTCBDE can be performed effectively and safely in elderly patients. METHODS: This is a retrospective study of patients who underwent LTCBDE for choledocholithiasis performed from January 2010 to December 2012. Patients of age 70 or older were included in the elderly group. The rest integrated the younger group. Demographic data and perioperative parameters were compared between groups. RESULTS: From January 2010 to December 2012, 171 patients admitted for choledocholithiasis and gallstone attempted a single-step treatment combining LTCBDE and laparoscopic cholecystectomy. There were 104 women (60.8%) and 67 men (39.2%) with a median age of 57 (range 24-87) years. Elderly patients had significantly more preoperative risk factors. However, there was no significant difference in the success rate of LTCBDE (96.9% versus 92.7%, P = .142) for the two groups. The operative time was a little longer in elderly group than in younger group: median 80 (60-110) minutes versus 70 (50-95) minutes, respectively (P < .001). Postoperative recovery was slower in elderly group than in younger group, as reflected by a longer median postoperative hospital stay (2 days versus 1 day, P < .001) and a higher rate of abdominal drain placed (17.1% versus 8.5%, P = .202). The rates of postoperative complications at discharge were similar between groups (3.0% versus 4.9%, P = .952). CONCLUSION: LTCBDE in the elderly patients is as effective and safe as in younger patients. PMID- 27672729 TI - Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review. AB - The growing multidisciplinary field of tissue engineering aims at predictably regenerating, enhancing, or replacing damaged or missing tissues for a variety of conditions caused by trauma, disease, and old age. One area of research that has gained tremendous awareness in recent years is that of platelet-rich fibrin (PRF), which has been utilized across a wide variety of medical fields for the regeneration of soft tissues. This systematic review gathered all the currently available in vitro, in vivo, and clinical literature utilizing PRF for soft tissue regeneration, augmentation, and/or wound healing. In total, 164 publications met the original search criteria, with a total of 48 publications meeting inclusion criteria (kappa score = 94%). These studies were divided into 7 in vitro, 11 in vivo, and 31 clinical studies. In summary, 6 out of 7 (85.7%) and 11 out of 11 (100%) of the in vitro and in vivo studies, respectively, demonstrated a statistically significant advantage for combining PRF to their regenerative therapies. Out of the remaining 31 clinical studies, a total of 8 reported the effects of PRF in a randomized clinical trial, with 5 additional studies (13 total) reporting appropriate controls. In those clinical studies, 9 out of the 13 studies (69.2%) demonstrated a statistically relevant positive outcome for the primary endpoints measured. In total, 18 studies (58% of clinical studies) reported positive wound-healing events associated with the use of PRF, despite using controls. Furthermore, 27 of the 31 clinical studies (87%) supported the use of PRF for soft tissue regeneration and wound healing for a variety of procedures in medicine and dentistry. In conclusion, the results from the present systematic review highlight the positive effects of PRF on wound healing after regenerative therapy for the management of various soft tissue defects found in medicine and dentistry. PMID- 27672730 TI - Isolation of baker's yeast mutants with proline accumulation that showed enhanced tolerance to baking-associated stresses. AB - During bread-making processes, yeast cells are exposed to baking-associated stresses such as freeze-thaw, air-drying, and high-sucrose concentrations. Previously, we reported that self-cloning diploid baker's yeast strains that accumulate proline retained higher-level fermentation abilities in both frozen and sweet doughs than the wild-type strain. Although self-cloning yeasts do not have to be treated as genetically modified yeasts, the conventional methods for breeding baker's yeasts are more acceptable to consumers than the use of self cloning yeasts. In this study, we isolated mutants resistant to the proline analogue azetidine-2-carboxylate (AZC) derived from diploid baker's yeast of Saccharomyces cerevisiae. Some of the mutants accumulated a greater amount of intracellular proline, and among them, 5 mutants showed higher cell viability than that observed in the parent wild-type strain under freezing or high-sucrose stress conditions. Two of them carried novel mutations in the PRO1 gene encoding the Pro247Ser or Glu415Lys variant of gamma-glutamyl kinase (GK), which is a key enzyme in proline biosynthesis in S. cerevisiae. Interestingly, we found that these mutations resulted in AZC resistance of yeast cells and desensitization to proline feedback inhibition of GK, leading to intracellular proline accumulation. Moreover, baker's yeast cells expressing the PRO1P247S and PRO1E415K gene were more tolerant to freezing stress than cells expressing the wild-type PRO1 gene. The approach described here could be a practical method for the breeding of proline-accumulating baker's yeasts with higher tolerance to baking-associated stresses. PMID- 27672731 TI - Fresh versus cryopreserved oocyte donation. AB - PURPOSE OF REVIEW: Utilization of cryopreserved instead of fresh donor oocytes has rapidly increased in recent years. Whether treatment outcomes are comparable has, however, remained controversial. RECENT FINDINGS: More than 24% of initiated oocyte donation cycles in the USA during 2013-2014 involved previously cryopreserved oocytes. The use of cryopreserved-donated oocytes may simplify logistics and lower costs per treatment cycle. Whether cryopreserved donor oocytes also lower costs per live birth is still undetermined as they result in lower live birth rates in comparison to fresh donor oocyte cycles. National data regarding the safety of donated oocytes, including miscarriage rates and neonatal health outcomes, are lacking. SUMMARY: Currently available data on cryopreserved donated oocytes are incomplete and, therefore, still insufficient to claim equivalency between fresh and cryopreserved donor oocytes. Until sufficient data are available, patients should be advised about advantages and disadvantages of both methods of oocyte donation, and the use of cryopreserved oocytes should be considered only with caution and appropriate informed consent. Because banking of donated human oocytes facilities their commercial trade, it challenges basic ethical considerations, which have been the basis of oocyte donation since its inception. PMID- 27672732 TI - Elective oocyte cryopreservation for deferred childbearing. AB - PURPOSE OF REVIEW: Elective oocyte cryopreservation for deferred childbearing has gained popularity worldwide, commensurate with increased knowledge regarding age related fertility decline. The purpose of this review is to summarize recent data regarding trends in delayed childbearing, review recent findings surrounding age related fertility decline, acknowledge significant gaps in knowledge among patients and providers regarding fertility decline and review outcomes following elective oocyte cryopreservation. RECENT FINDINGS: Despite an inevitable decline in fertility and increase in miscarriage with increasing female age, there is a growing worldwide trend to delay childbearing. Patients and providers alike demonstrate large gaps in knowledge surrounding age-related fertility decline. Oocyte cryopreservation is clinically approved for medically indicated fertility preservation, but a growing number of women are using oocyte cryopreservation to defer childbearing and maintain reproductive autonomy. Mounting data support the efficacy and safety of oocyte cryopreservation when used to electively defer childbearing, with recent studies demonstrating rates of euploidy, implantation and live birth rates equivalent to in-vitro fertilization (IVF) with fresh oocytes. SUMMARY: Oocyte cryopreservation provides women with an option to defer childbearing and maintain reproductive autonomy, with IVF success rates on par with fresh IVF. However, it is critical that patients understand the limitations of oocyte cryopreservation. Greater education regarding age-related fertility decline should be geared toward patients and providers to prevent unintended childlessness. PMID- 27672733 TI - A haploid HSV-1 genome platform for vector development: testing of the tetracycline-responsive switch shows interference by infected cell protein 0. AB - BACKGROUND: Although herpes simplex virus type 1 (HSV-1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of approximately 15.4 kb of DNA sequences that are duplicated in the HSV 1 genome, complicating vector construction and stability. METHODS: As a useful platform for building HSV-1 vectors, we have constructed a fully haploid HSV-1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired. We used this DeltaIR mutant to subsequently investigate whether the insertion of tetracycline-responsive tetO elements into the ICP34.5-ICP0 gene region can be used to control HSV-1 lytic replication. RESULTS: The results of the present study show that DeltaIR mutants deleted for ICP34.5 are viable for replication but not when the ICP0 promoter is also disrupted, thus indicating that regulation of infected cell protein 0 (ICP0) levels in the absence of ICP34.5 could be a viable means for controlling growth of HSV-1 vectors. Surprisingly, however, the tetO elements inserted into the ICP0 promoter did not confer ligand responsiveness to growth or ICP0 expression. Further analysis by transfection experiments revealed that ICP0 itself interferes with the tetracycline switch and reduces the the inducibility of this system. CONCLUSIONS: Our new haploid HSV-1 BAC is a useful platform for building multiply deleted HSV-1 vectors. Deletion of the gene for ICP34.5 in this backbone renders viral growth dependent on ICP0, although ICP0 expression could not be regulated by tet-responsive transcriptional regulators. PMID- 27672734 TI - Objective outcome and quality-of-life assessment in women with repeat incontinence surgery. AB - AIMS: To evaluate subjective and objective outcome after repeat surgery for stress urinary incontinence (SUI). METHODS: Patients who underwent a midurethral tape after failed Burch colposuspension or failed midurethal tape between 1999 and 2014 were invited for follow-up. Urogynecological examination and urodynamics was performed, and objective cure was defined as a negative cough stress test; subjective cure was defined as negotiation of SUI symptoms. Quality-of-life (QoL), sexual health, and subjective success was assessed with the King's Health Questionnaire, Incontinence Outcome Questionnaire, Female Sexual Function Index, and the Patient Global Impression of Improvement (PGI-I) score. RESULTS: Overall 52 women underwent repeat incontinence surgery. Out of the 44 women still alive, 33 (75%) were available for follow-up. All 33 women completed the questionnaires; 23 women (70%) attended the clinic and also had an urogynecological examination. At a median follow-up of 11 years, subjective cure was 67% (22/33), objective cure was 65% (16/23), and subjective success according to PGI-I was 78% (18/23), with no significant differences between groups. No erosions of suture or tape material into the bladder, urethra, or vagina were seen. Two women had received a third anti-incontinence operation with TVT after failed tape after failed Burch, and were continent at follow-up. Two women with tape after colposuspension required division of the tape and both were continent at the time of follow-up. With regard to QoL and sexual health, no significant differences were seen for most domains. CONCLUSIONS: Midurethral tapes are an option for women with recurrent SUI after previous colposuspension or midurethral tape. PMID- 27672735 TI - Growth in the global N2 sink attributed to N fertilizer inputs over 1860 to 2000. AB - Cropland expansion and fertilizer applications are among the most important substantial effects of human actions on the global nitrogen (N) cycle. However, questions remain over the fate of anthropogenic N inputs, particularly whether a significant fraction of N-based fertilizers have been lost to inert N2 or reactive N forms. Here, we combine natural N isotope constraints on the pre industrial N cycle with global mass-balance modeling to investigate the role of cropland conversion on gaseous N emissions and hydrological N leaching fluxes. We estimate that cropland expansion has been accompanied by >9-fold increase in N input rates to cropping systems, roughly doubling the baseline N budget of the terrestrial biosphere. As a consequence, approximately 10 times more N is exported from modern croplands to the hydrosphere than in 1860, with a five-fold increase in cropland N gases emission to the atmosphere. Atmospheric NH3, NO, N2O and N2 fluxes increased from 8.6, 16.6, 11.7 and 31.9TgNyr-1, respectively, in 1860 to 17.7, 23.6, 15.2 and 39.7TgNyr-1, respectively, by 2000. Thus, the growth in N2 accounted for ~20% of cropland-driven N losses (dissolved plus gaseous pathways), with the remaining 80% exported as reactive N forms. Although the increase in N2 emissions has mitigated some of the unwanted side-effects of N fertilizer applications on human health, the economy, and climate change, this inert sink has been unable to keep pace with the increase in N inputs for enhanced food production. Our results imply that, unless new management steps are taken, an increasing fraction of N fertilizers will mobilize to reactive N forms in the global land, air and water systems, thus further accelerating the negative consequences of human modifications of the N cycle this century. PMID- 27672736 TI - A critical review of approaches and limitations of inhalation bioavailability and bioaccessibility of metal(loid)s from ambient particulate matter or dust. AB - Inhalation of metal(loid)s in ambient particulate matter (APM) represents a significant exposure pathway to humans. Although exposure assessment associated with this pathway is currently based on total metal(loid) content, a bioavailability (i.e. absorption in the systemic circulation) and/or bioaccessibility (i.e. solubility in simulated lung fluid) based approach may more accurately quantify exposure. Metal(loid) bioavailability-bioaccessibility assessment from APM is inherently complex and lacks consensus. This paper reviews the discrepancies that impede the adoption of a universal protocol for the assessment of inhalation bioaccessibility. Exposure assessment approaches for in vivo bioavailability, in-vitro cell culture and in-vitro bioaccessibility (composition of simulated lungs fluid, physico-chemical and methodological considerations) are critiqued in the context of inhalation exposure refinement. An important limitation of bioavailability and bioaccessibility studies is the use of considerably higher than environmental metal(loid) concentration, which diminishing their relevance to human exposure scenarios. Similarly, individual metal(loid) studies have been criticised due to complexities of APM metal(loid) mixtures which may impart synergistic or antagonistic effects compared to single metal(loid) exposure. Although a number of different simulated lung fluid (SLF) compositions have been used in metal(loid) bioaccessibility studies, information regarding the comparative leaching efficiency among these different SLF and comparisons to in-vivo bioavailability data is lacking. In addition, the particle size utilised is often not representative of what is deposited in the lungs while assay parameters (extraction time, solid to liquid ratio, temperature and agitation) are often not biologically relevant. Research needs are identified in order to develop robust in-vitro bioaccessibility protocols for the assessment or prediction of metal(loid) bioavailability in APM for the refinement of inhalation exposure. PMID- 27672737 TI - Combining land use regression models and fixed site monitoring to reconstruct spatiotemporal variability of NO2 concentrations over a wide geographical area. AB - The epidemiological research benefits from an accurate characterization of both spatial and temporal variability of exposure to air pollution. This work aims at proposing a method to combine the high spatial resolution of Land Use Regression (LUR) models with the high temporal resolution of fixed site monitoring data, to model spatiotemporal variability of NO2 over a wide geographical area in Northern Italy. We developed seasonal LUR models to reconstruct the spatial distribution of a scaling factor that relates local concentrations to those measured at two reference central sites, one for the northern flat area and one for the southern mountain area. We calculated the daily average concentrations at 19 locations spread over the study areas as the product of the local scaling factor and the reference central site concentrations. We evaluated model performance comparing modeled and measured NO2 data. LUR model's R2 ranges from 0.76 to 0.92. The main predictors refers substantially to traffic, industrial land use, buildings volume and altitude a.s.l. The model's performance in reproducing measured concentrations was satisfactory. The temporal variability of concentrations was well captured: Spearman correlation between model and measures was >0.7 for almost all sites. Model's average absolute errors were in the order of 10MUgm-3. The model for the southern area tends to overestimate measured concentrations. Our modeling framework was able to reproduce spatiotemporal differences in NO2 concentrations. This kind of model is less data-intensive than usual regional atmospheric models and it may be very helpful to assess population exposure within studies in which individual relevant exposure occurs along periods of days or months. PMID- 27672738 TI - A message from the ground electrode. PMID- 27672739 TI - [Teaching in Perspective - How Medical Students Assess Their Practical Clinical Training in Surgery]. AB - Introduction: Practical clinical expertise is a crucial part of medical professionalism. Several studies have shown that medical students are poorly trained in practical skills during their undergraduate training. Even the students rated their own expertise in practical skills as poor. The amendments to the German Regulating Licenses in Practical Medicine are intended to strengthen practical clinical training. The aim of the present study is to use focus groups to analyse practical clinical training with respect to organisation, difficulties and problems from the learners' perspective. Methods: The present qualitative study uses the focus group approach. Each focus group was composed of a maximum of 6 students per group with the same level of training. Using a standardised interview manual, a total of 31 students and four first-year residents participated in the study. Data interpretation was performed using structured qualitative content analysis. Results: The present work demonstrates that students of all levels of training greatly value their training in practical clinical expertise, especially in clinical skills. Due to the lack of defined learning objectives for practical skills, students training in clinical internships and medical registrar positions are highly dependent on the motivation and interest of the individual clinical teacher and the learner himself. Students struggle to estimate their actual level of expertise due to the lack of defined learning objectives. This is exacerbated by the fact that students rarely receive feedback about their expertise. Students complain that many teachers do not know the level of training required of their students. Conclusion: The definition of basic and specific learning objectives and the communication of this between learners and teachers is an essential part of practical clinical training. PMID- 27672740 TI - Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment. AB - Despite the substantial benefit of androgen deprivation therapy (ADT) for metastatic prostate cancer, patients often progress to castration-resistant disease (CRPC) that is more difficult to treat. CRPC is associated with renewed androgen receptor activity in tumor cells and restoration of tumor androgen levels through acquired intratumoral steroidogenesis (AIS). Although prostate cancer (PCa) cells have been shown to have steroidogenic capability in vitro, we previously found that benign prostate stromal cells (PrSCs) can also synthesize testosterone (T) from an adrenal precursor, DHEA, when stimulated with a hedgehog (Hh) pathway agonist, SAG. Here, we show exposure of PrSCs to a different Smoothened (Smo) agonist, Ag1.5, or to conditioned medium from sonic hedgehog overexpressing LNCaP cells induces steroidogenic enzyme expression in PrSCs and significantly increases production of T and its precursor steroids in a Smo dependent manner from 22-OH-cholesterol substrate. Hh agonist-/ligand-treated PrSCs produced androgens at a rate similar to or greater than that of PCa cell lines. Likewise, primary bone marrow stromal cells became more steroidogenic and produced T under the influence of Smo agonist. Treatment of mice bearing LNCaP xenografts with a Smo antagonist, TAK-441, delayed the onset of CRPC after castration and substantially reduced androgen levels in residual tumors. These outcomes support the idea that stromal cells in ADT-treated primary or metastatic prostate tumors can contribute to AIS as a consequence of a paracrine Hh signaling microenvironment. As such, Smo antagonists may be useful for targeting prostate tumor stromal cell-derived AIS and delaying the onset of CRPC after ADT. PMID- 27672742 TI - Pretreatment Tumor Thickness as a Predictor of Pathologic Complete Response to Neoadjuvant Chemoradiation Therapy for Stage II/III Rectal Adenocarcinoma. AB - OBJECTIVES: To evaluate pretreatment tumor thickness in predicting pathologic complete response (pCR) of stage II/III rectal adenocarcinoma to neoadjuvant chemoradiation (chemoradiotherapy [CRT]). METHODS: We retrospectively analyzed 185 patients who were diagnosed with stage II or III rectal adenocarcinoma from January 2011 to July 2013 and treated with neoadjuvant intensity-modulated radiation therapy (45 Gy in 1.8-Gy fractions to pelvis and 50 Gy in 2-Gy fractions to rectal tumor as an integrated boost) or 3 dimensionally conformal radiation therapy (45 Gy in 1.8-Gy fractions to pelvis followed by an additional 5.4-Gy to rectal tumor) concurrently with two 3-week cycles of chemotherapy (oxaliplatin 130 mg/m on day 1 and capecitabine 825 mg/m, twice per day from day 1 to 14, cycle 2 starts on week 4). One week after CRT, 36% patients received 1 more cycle of the above chemotherapy and 55% received 1 to 2 cycles of FOLFOX6. Tumor response was categorized as pCR and non-pCR. Tumor thickness measured on magnetic resonance imaging was collected. A multivariate logistic regression model was used to evaluate the association of potential predictors and pCR. RESULTS: Thirty-eight patients (20.5%) reached pCR. Multivariate analysis found the pretreatment tumor thickness to be associated with higher probability of pCR after adjusting for radiation therapy-surgery interval time and pretreatment carcino-embryonic antigen level. The pretreatment carcino-embryonic antigen level was associated with pCR in the univariate analysis but lost the association in the multivatiate model. The pretreatment T or N stage, tumor volume, distance from tumor to anal verge, craniocaudal length of tumor, radiation therapy technique, and patient age and sex were not associated with pCR. CONCLUSIONS: We concluded that pretreatment tumor thickness is an independent predictor for pCR of stage II/III rectal adenocarcinoma to the neoadjuvant CRT. PMID- 27672741 TI - Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models? AB - PURPOSE OF REVIEW: Anti-nerve growth factor (NGF) antibodies hold tremendous potential for the management of osteoarthritis pain, but clinical trials have revealed serious adverse effects that are incompletely understood. This review discusses clinical trial results along with preclinical studies that have assessed NGF blockade in experimental osteoarthritis, in order to provide insight for future studies. RECENT FINDINGS: Systematic reviews have revealed that anti NGF therapy, including tanezumab, is efficacious in improving pain and function, but serious adverse events, including rapidly progressive osteoarthritis and osteonecrosis, resulted in a moratorium on trials that was only recently lifted. Within the past year, preclinical testing has revealed effects of NGF blockade on both pain behaviors and joint structure in experimental models of osteoarthritis. Similar to clinical trial results, these studies in laboratory animals demonstrated analgesic efficacy of NGF blockade. Interestingly, several animal studies have suggested detrimental effects on joint integrity as a result of treatment, particularly when treatment is started early in the disease, when joint damage is mild to moderate. SUMMARY: NGF blockade continues to represent a promising new approach for the treatment of osteoarthritis pain, but the actual benefits and risks remain to be fully elucidated. Preclinical models may suggest patient populations that could be best served while limiting side-effects, but future work should further investigate the mechanisms of benefits and unwanted side-effects. PMID- 27672743 TI - Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience. AB - OBJECTIVES: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. MATERIALS AND METHODS: From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. RESULTS: The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4 99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2 96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. CONCLUSIONS: Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients. PMID- 27672744 TI - Controversies of Scoliosis Management in Duchenne Muscular Dystrophy. PMID- 27672745 TI - Participation in Daily Life: Influence on Quality of Life in Ambulatory Children with Cerebral Palsy. PMID- 27672746 TI - Incidence of Tethered Cord in Toe Walking: Single Center Experience at Gillette Children's Specialty Healthcare. PMID- 27672747 TI - Impact of Selective Percutaneous Myofascial Lengthening (SPML) on Quality of Life in Children with Cerebral Palsy. PMID- 27672748 TI - Treatment with Botulinum Toxin Type A in Infants with Refractory Congenital Muscular Torticollis: A 10-Year Retrospective Study. PMID- 27672749 TI - Stimulation Across the Transverse Carpal Ligament in Carpal Tunnel Syndrome. PMID- 27672750 TI - The Effect of Vitamin D Supplementation on Pain, Mood, Depression, and Strength in Patients with Spinal Cord Injury. PMID- 27672751 TI - Spinal Cord Injuries Related to 2015 Nepal Earthquakes. PMID- 27672752 TI - Epidemiology of Fractures in Men with Spinal Cord Injury. PMID- 27672753 TI - A Randomized Comparison of Locomotor Therapy Interventions: Partial Body Weight Supported Treadmill, Lokomat(r) and G-Eo(r) Training in Traumatic Brain Injury. PMID- 27672754 TI - Softball Windmill Pitchers: Strength and Motion in the Dominant Versus Non Dominant Upper and Lower Extremity. PMID- 27672755 TI - Inflammatory Biomarkers in Acute Myofascial Pain. PMID- 27672756 TI - Adolescents and Adults with Patellofemoral Pain Have Different Pathological Knee Kinematics. PMID- 27672757 TI - Long-Term Outcome of Ultrasound Therapy for Calcific Tendinitis of the Shoulder: Results of a RCT. PMID- 27672758 TI - Concussion-Like Symptom Reporting in High School Student Athletes with ADHD. PMID- 27672759 TI - The Impact of Axial Injury, Extra-Axial Injury, and Combined Injury on Functional Status in Traumatic Brain Injury (TBI). PMID- 27672760 TI - Stroke Acute Rehabilitation: Factors Associated with Discharge to Home vs Long Term Care. PMID- 27672761 TI - A Comparison of Outcomes Between Glioblastoma Multiforme and Other Neurological Patients in the Acute Rehabilitation Setting. PMID- 27672762 TI - Cortical Neurochemical Profile Depends on the Origin and the Site of the Central Nervous System Injury. PMID- 27672763 TI - Effects of Forced Use on the Ventral Premotor Cortex Distal Forelimb Representation After Ischemic Infarct in Primary Motor Cortex. PMID- 27672764 TI - Effect of Wheelchair Stroke Pattern on Arm Muscle Fatigue. PMID- 27672766 TI - Variability Among Pain and Function Assessment Tools for Tracking Improvement of Lumbar Stenosis Patients After Surgery. PMID- 27672765 TI - The Utilization of Medications in Patients with Back Pain: Implications in Choice of Analgesia and Conditions Beyond Back Pain. PMID- 27672767 TI - Patient and Procedural Risk Factors for Cortisol Suppression Following Epidural Steroid Injections for Spinal Stenosis. PMID- 27672768 TI - Interventional Treatment and Physical Therapy Utilization for Degenerative Lumbar Spondylolisthesis Within Medicare Beneficiaries From 2000-2011: Descriptive Analysis and Impacts on Surgery Frequency. PMID- 27672769 TI - Poster 1 Incomplete Right Brachial Plexopathy after Segmental Mastectomy for Breast Cancer Resection: A Case Report. PMID- 27672770 TI - Poster 3 Multifocal Ischemic CVAs in a Patient with Amyloid Beta Related Angiitis. PMID- 27672771 TI - Poster 2 Charles Bonnet Syndrome Decreasing Functional Independence Measure Efficiency in the Inpatient Brain-Injury Rehabilitation Setting: Case Report. PMID- 27672772 TI - Poster 4 The Domains of Dyspnea Measurement, According to the American Thoracic Society. PMID- 27672773 TI - Poster 5 Evaluation of Depressive Symptoms, Pain and Function in Elders with Chronic Knee Osteoarthritis. PMID- 27672774 TI - Poster 6 A Correlative Study of the Pain Disability Questionnaire and the Clinician-Derived Physical Performance Tests on Elderly Individuals with Chronic Pain and Cardio-Pulmonary Disorder. PMID- 27672775 TI - Poster 8 The STEADI Measure from the Center for Disease Control & Prevention (CDC) and Its Correlation with Clinical Observation Assessments. PMID- 27672776 TI - Poster 7 A Correlative Study of the International Classification of Functioning (ICF) Domains with the Whole Person Impairment in Individuals with Chronic Pulmonary Disorders. PMID- 27672777 TI - Poster 9 Bilateral Hip Heterotopic Ossification Following Lung Transplantation: A Case Report. PMID- 27672778 TI - Poster 11 A Rare Case of Chronic Inflammatory Demyelinating Polyneuropathy in the Setting of SLE: A Case Report. PMID- 27672779 TI - Poster 12 Three-Dimensional (3D) Printed Prosthetics Offer Functional Improvement in Individuals with Upper Extremity Limb Loss: A Case Series. PMID- 27672780 TI - Poster 10 Successful Rehabilitation Outcome from Rare Brain Tumor (Intracranial Follicular Dendritic Cell Sarcoma): A Case Report. PMID- 27672781 TI - Poster 14 Loss of Mobility Secondary to Multiple Spinal Fusions in a Patient with DYT1/DYT-TOR1A Isolated Early Onset Dystonia: A Case Report. PMID- 27672783 TI - Poster 13 Factors Associated with Discharge to Home Versus Discharge to Institutional Care for Inpatient Rehabilitation Patients Admitted Directly from Skilled Nursing Facilities. PMID- 27672782 TI - Poster 15 Women with Neurologic Disabilities: What are the Barriers to Breast Health Screening? PMID- 27672784 TI - Poster 17 Acute Respiratory Failure Following Bilateral Diaphragmatic Paralysis Treated with Tracheostomy and Left Hemidiaphragmatic Plication: A Case Report. PMID- 27672785 TI - Poster 16 Effect of Cancer-Related Fatigue on Cytokine Reactivity to Challenge Tasks in Breast Cancer Survivors. PMID- 27672786 TI - Poster 18 Buried Bumper Syndrome in a Traumatic Spinal Cord Injury Patient: A Case Report. PMID- 27672787 TI - Poster 19 Unexpected Return of Hearing Following Motor Vehicle Collision: A Case Report. PMID- 27672788 TI - Poster 21 Leptomeningeal Carcinomatosis Presenting as Tetraparesis: A Very Rare Case of Small Cell Prostate Carcinoma. PMID- 27672789 TI - Poster 20 Impact of a Structured Rehabilitation Protocol on Hernia Recurrence after Operative Repair. PMID- 27672790 TI - Poster 22 The Effects of Underwater Treadmill Therapy on the Rehabilitation of a Polytrauma Patient: A Case Report. PMID- 27672791 TI - Poster 23 An Unusual Cause of Leg Pain in a Stroke Patient: A Case Report. PMID- 27672792 TI - Poster 25 Predicting Return to Medical Service Among Dysvascular Lower Extremity Amputees on an Acute Inpatient Rehabilitation Unit. PMID- 27672793 TI - Poster 24 The Role of the Spinal Cord Injury Care Provider in Safeguarding Patient's Best Interests and Values: A Case Report and Discussion in Palliative Wound Care. PMID- 27672794 TI - Poster 26 A Randomized Trial of Cardiac Rehabilitation for Adolescents and Adults with Congenital Heart Disease. PMID- 27672795 TI - Poster 27 Acupuncture Treatment for Levator Ani Syndrome: A Case Report. PMID- 27672796 TI - Poster 28 Steroid-Induced Myopathy from Endogenous Hypercortisolism Secondary to Adrenocortical Carcinoma: A Case Report. PMID- 27672797 TI - Poster 31 Taxane-Induced Myositis: A Case Report. PMID- 27672798 TI - Poster 30 Use of Delirium Triggering Medications Among Patients with Delirium at Admission to Inpatient Rehabilitation Facility. PMID- 27672799 TI - Poster 29 The Over Utilization of PPIs in an Acute Rehabilitation Hospital and How to Fix it! PMID- 27672800 TI - Poster 32 Functional Consequences of Permanent Paraplegia Following Nelaribine Treatment in T-Cell Acute Lymphoblastic Leukemia: A Case Report. PMID- 27672801 TI - Poster 33 Feasibility, Safety and Acceptance of an Immediate Fit Adjustable Transtibial Prosthesis: A Case Report. PMID- 27672802 TI - Poster 34 The Rehabilitation of a Quadruple Amputee Patient Due to Limb Ischemia from Vasopressor use During Septic Shock: A Case Report. PMID- 27672803 TI - Poster 35 An Increased Incidence of Neuralgic Amyotrophy. PMID- 27672804 TI - Poster 36 Meta-Analysis of the Association Between Major Depression and Neurocognitive Test Performances. PMID- 27672806 TI - Poster 40 Seat Elevator Procurement and its Association with Functional Mobility. PMID- 27672805 TI - Poster 37 Relationship Between VTE Prophylactics and Ambulation following Ischemic Acute Stroke. PMID- 27672807 TI - Poster 38 Anticoagulation: Hemorrhagic Conversion and VTE following Acute Ischemic Stroke. PMID- 27672808 TI - Poster 39 The Assessment of Pain and Quality of Life in Cancer Patients. PMID- 27672810 TI - Poster 42 Differentiation of Central and Peripheral Fatigue in Breast Cancer Survivors. PMID- 27672809 TI - Poster 43 Massive Mortality Risk Not a Barrier to Acute Rehabilitation: A Case Report. PMID- 27672811 TI - Poster 41 Pathologic Vertebral Body Fracture after Chronic Steroid Use in an Older Adult with Orthotopic Heart Transplant: A Case Report. PMID- 27672812 TI - Poster 45 Utilization and Management of Urine Drug Screening for Opioid Medications. PMID- 27672813 TI - Poster 46 Multiple Amputations Including Bilateral Transtibial Amputations in a 29-Year-Old Female After Suffering Placental Abruption, GBS Septicemia and DIC: A Case Report. PMID- 27672815 TI - Poster 47 Acute Regression in Cognition and Language in Patient with TBI after Discontinuation of Donepezil: A Case Report. PMID- 27672814 TI - Poster 44 Pilot Comparative Study of Two Robot-Assisted Therapies in Patients with Chronic Stroke. PMID- 27672817 TI - Poster 49 Psoas Urinoma as an Unusual Etiology for Hip Weakness: A Case Report. PMID- 27672816 TI - Poster 48 A Novel Presentation of Acute Motor Axonal Neuropathy: A Case Report. PMID- 27672819 TI - Poster 53 Daptomycin-Induced Acute Eosinophilic Pneumonia in a Patient Receiving Rehabilitation Post Prosthetic Joint Infection: A Case Report. PMID- 27672818 TI - Poster 50 Torsional Anatomy of the Lower Limb: The Appearance of Anatomy in Hemispastic Position. PMID- 27672820 TI - Poster 52 Acute Hallucinosis Related to Amantadine Use in the Setting of Traumatic Brain Injury: A Case Report. PMID- 27672821 TI - Poster 51 Sleep Quality and Functional Outcome Measures, an Ongoing Prospective IRB Study. PMID- 27672822 TI - Poster 54 The Impact of Routine Lower Extremity Deep Vein Thrombosis Screening on Acute Rehabilitation Admissions. PMID- 27672823 TI - Poster 55 Role of d-Dimer in Evaluation of Deep Vein Thrombosis When Venous Duplex Study is Negative: A Case Report. PMID- 27672824 TI - Poster 56 An Unusual Presentation of Residual Limb Pain Relieved by Botulinum Toxin Injection: A Case Report. PMID- 27672825 TI - Poster 57 Discrepancy Between Muscle Grade and Compound Muscle Action Potential Amplitude on Nerve Conduction Study: A Case Report. PMID- 27672826 TI - Poster 59 Acute Diffuse Tendinopathy Causing Systemic Weakness and Pain Secondary to Ciprofloxacin Use: A Case Report. PMID- 27672827 TI - Poster 60 Defining Safe Head-of-the-Bed Inclination in Patients with Decubitus Wounds Laying on a Dolphin Fluid Immersion Simulation Mattress Using Pressure Mapping: A Case Series. PMID- 27672828 TI - Poster 58 Very Early Surgical Excision of Heterotopic Ossification during Inpatient Rehabilitation 7 Weeks After Diagnosis in a Patient with Left Acromioclavicular Fracture and Spinal Cord Injury: A Case Report. PMID- 27672829 TI - Poster 63 Vertebral Artery Dissection Resulting in Cerebellar CVA after Chiropractic Manipulation in a Patient with Fibromuscular Dysplasia. PMID- 27672830 TI - Poster 61 Higher Dietary Intake of Vitamin D May Influence Cholesterol and Insulin Sensitivity Independent of Body Composition in Men with Chronic Spinal Cord Injury. PMID- 27672831 TI - Poster 62 Muscle Weakness, Dysarthria, and Dysphagia After Methotrexate Toxicity: A Case Report. PMID- 27672832 TI - Poster 66 Comprehensive Prevention and Management of Pressure Ulcers in an Acute Inpatient Rehabilitation Facility: An Evidence -Based Assessment. PMID- 27672833 TI - Poster 64 Ischemic Stroke after Routine Cardiac Catheterization: A Case Report. PMID- 27672834 TI - Poster 65 Potential Predictors of General and Instrumented Activities of Daily Living in Patients with Stroke: A Follow-Up Study. PMID- 27672835 TI - Poster 67 Runner's Dystonia Presenting as Leg Pain: A Case Report. PMID- 27672836 TI - Poster 68 Feasibility of a Prehabilitation Program for Patients with Potentially Resectable Pancreatic Cancer: Pilot Study. PMID- 27672837 TI - Poster 70 Bladder Herniation Masked by Colonic Ileus: A Case Report. PMID- 27672838 TI - Poster 69 Regaining Independence in Adult Onset Still's Disease: A Case Report. PMID- 27672839 TI - Poster 71 New Frontiers: Inpatient Comprehensive Rehabilitation After Full Face Transplantation: A Case Report. PMID- 27672840 TI - Poster 72 Teetering on the Edge: Rehabilitation in a Medically Complex Patient with Familial Dysautonomia (Hereditary Sensory Autonomic Neuropathy Type III): A Case Report. PMID- 27672841 TI - Poster 75 Evaluating the STOP SEPSIS Protocol on Spinal Cord and Traumatic Brain Injury Rehabilitation Units. PMID- 27672842 TI - Poster 74 Van Nes Rotationplasty in Skeletally Mature Patient: A Case Report. PMID- 27672844 TI - Poster 77 Corpus Callosum Stroke. PMID- 27672843 TI - Poster 73 Extensive Morel Lavallee Lesion over the Spine Secondary to Motor Vehicle Crash Involving Ejection: A Case Report. PMID- 27672845 TI - Poster 76 An Active Overlay for Pressure Ulcer Prevention in Patients with Spinal Cord Injury. PMID- 27672846 TI - Poster 78 Novel Bimodal Technology Addresses Vitamin D Malabsorption. PMID- 27672847 TI - Poster 81 Heart of the Matter. Atypical Mechanisms of Amputation in Young Adults. A Review of Two Case Reports. PMID- 27672848 TI - Poster 79 Comprehension of Visual Displays of the Functional Independence Measure (FIM) in Patients with Spinal Cord Injury in Acute Rehabilitation. PMID- 27672849 TI - Poster 80 Bilateral Lower Extremity Amputation after Toxic Shock Syndrome Presents with Locked Knee: A Case Report. PMID- 27672850 TI - Poster 83 Management of Necrotic Digits on the Inpatient Rehabilitation Unit. PMID- 27672851 TI - Poster 84 Lumbar Plexopathy Secondary to Psoas Mass: A Case Report. PMID- 27672852 TI - Poster 82 Bilateral Upper Trunk Plexopathy with a Winged Scapula: A Case Report. PMID- 27672853 TI - Poster 85 A Unique Diagnosis of Critical Illness Neuromyopathy in a Patient with Wegener's Granulomatosis: A Case Report. PMID- 27672854 TI - Poster 86 Assessing the Relationship Between Emotional Adjustment, Participation, and Function Through the Use of a Psychosocial Adjustment Scale During Acute Rehabilitation. PMID- 27672855 TI - Poster 87 Post-Infectious Cerebellar Ataxia in a Young Male: A Case Report. PMID- 27672856 TI - Poster 90 A Multidisciplinary Team Approach to Admitting Complex Patients to Inpatient Rehabilitation: A Quality Improvement Pilot Study. PMID- 27672858 TI - Poster 88 Gait Analysis after Bilateral Quadriceps Tendon Rupture in a Patient Who Elected to be Conservatively Managed: A Case Report. PMID- 27672857 TI - Poster 89 Functional Outcomes with Acute Inpatient Prosthetic Gait Training for Lower Extremity Amputees. PMID- 27672859 TI - Poster 92 Identifying Nonhereditary Myositis Ossificans Traumaticus in a Community Hospital. PMID- 27672860 TI - Poster 91 Progressive Quadriparesis, Bulbar Dysfunction, and Paresthesias in a Female with History of Sjogren's Syndrome: A Case Report. PMID- 27672861 TI - Poster 95 Oncologist's Attitude and Knowledge about Cancer Rehabilitation. PMID- 27672862 TI - Poster 94 Mononeuritis Multiplex Secondary to HCV Cryoglobulinemia and Rheumatoid Vasculitis: A Case Report. PMID- 27672863 TI - Poster 93 Rare Presentation of Three Limb Compartment Syndrome: A Case Report. PMID- 27672864 TI - Poster 97 Statin-Induced Rhabdomyolysis Triggered by Concomitant Colchicine Administration: A Case Report. PMID- 27672865 TI - Poster 96 Medial Pectoral Nerve Mononeuropathy: A Case Report. PMID- 27672866 TI - Poster 98 Cerebral Infarction Secondary to Cement Embolism Through a Patent Foramen Ovale After Percutaneous Kyphoplasty: A Case Report. PMID- 27672867 TI - Poster 100 Melanoma in Lower Limb Deformity- M.I.L.D. Physiatry Assessment and Treatment. PMID- 27672868 TI - Poster 101 Osteoporosis and Bisphosphonate Therapy: Friend or Foe? A Case Report. PMID- 27672869 TI - Poster 99 Identification of Acute Inpatient Rehabilitation Targets in Morbidly Obese Trauma Patients. PMID- 27672870 TI - Poster 102 The Functional Impairments in a Patient with the Rare Morvan's Syndrome: A Case Report. PMID- 27672871 TI - Poster 103 SCI Clinical Video to Home Telehealth: Promoting Wellness and Care Coordination. PMID- 27672872 TI - Poster 104 Early Mobility Considerations and Psychological Outcomes in Critically Ill Patients. PMID- 27672874 TI - Poster 107 Bilateral Brachial Plexus Injury: Tumor, Traction or Parsonage Turner. A Case Report. PMID- 27672873 TI - Poster 105 Chronic Leg Weakness Complicated by Rhabdomyolysis as a Result of Gitelman Syndrome: A Case Report. PMID- 27672875 TI - Poster 106 Transfemoral Socket Volume Management: Comparing A Traditional and Novel Socket Design Through: A Case Report. PMID- 27672876 TI - Poster 109 Confirmatory Factor Analysis of 12-Item WHO Disability Assessment Schedule (WHODAS 2.0) in Patients with Musculoskeletal Pain Conditions. PMID- 27672877 TI - Poster 108 Functional Outcomes of Inpatient Rehabilitation Following Bilateral Total Knee Arthroplasty. PMID- 27672878 TI - Poster 110 Acute Rehabilitation of MI Complicated by Cardiogenic Shock Requiring ECMO, Resulting in Necrotizing Fasciitis and AKA with Subsequent LifeVest Placement: A Case Report. PMID- 27672879 TI - Poster 113 Importance of a Physiatric Exam in a Patient with Shoulder Pain: A Case Report. PMID- 27672880 TI - Poster 111 Ultrasonographic Finding of Ischiofemoral Impingement Syndrome and Novel Treatment With Botulinum Toxin: A Case Report. PMID- 27672881 TI - Poster 112 An Uncommon Cause of Hip Pain in a Patient with Normal Bone Density: A Case Report. PMID- 27672882 TI - Poster 116 Ultrasound Verification of Palpatory Rib Identification for Safe Needle Examination of the Rhomboid Major Muscle. PMID- 27672883 TI - Poster 114 Atypical Upper Extremity Weakness After a Fall: A Case Report. PMID- 27672884 TI - Poster 115 A Unique Case of Snapping Scapula Syndrome in a Non-Overhead Athlete: A Case Report. PMID- 27672885 TI - Poster 119 Pathological Patellofemoral Kinematics Contribute to Idiopathic Patellofemoral Pain in Adolescence and Persist at Four Year Follow-up. PMID- 27672886 TI - Poster 118 Ultrasound-Guided Proximal Tibiofibular Joint Injection in the Management of Proximal Tibiofibular Joint Arthritis and Instability: A Case Report. PMID- 27672887 TI - Poster 117 Self-Reported Hip Problems in Professional Ballet Dancers: The Impact on Quality of Life. PMID- 27672888 TI - Poster 121 Musculoskeletal Physical Exam Skills Assessment in Physiatry Residents. PMID- 27672889 TI - Poster 122 The Utilization of Medications in Patients with Knee Osteoarthritis: Implications in Choice of Analgesia and Conditions Beyond Knee Pain. PMID- 27672890 TI - Poster 123 Ultrasound Guided Cryoablation of a Traumatic Hip Disarticulation Neuroma: A Case Report. PMID- 27672891 TI - Poster 126 Atypical Etiology and Presentation of an Acetabular Labral Tear of the Hip: A Case Report. PMID- 27672892 TI - Poster 125 Rehabilitation Approach and Management of Dermatomyositis: A Case Report. PMID- 27672893 TI - Poster 124 Use of Diagnostic Ultrasound for an Atypical Presentation of Low Back Pain in a Young Adult Male: A Case Report. PMID- 27672894 TI - Poster 128 Efficacy of Low Intensity Pulsed Ultrasound in Knee Osteoarthritis: A Crticial Review. PMID- 27672895 TI - Poster 129 Assessment of Introductory Residency Musculoskeletal Ultrasound Curriculum. PMID- 27672896 TI - Poster 127 Proximal Iliotibial Band Rupture Secondary to Chronic Steroid Use: A Case Report. PMID- 27672897 TI - Poster 132 A Juxta-Articular Cyst of the Hip Causing Sciatic Nerve Compression in a Master Athlete: A Case Report. PMID- 27672898 TI - Poster 130 A Rare Cause of Hip Pain in a Young Male. A Case Report. PMID- 27672899 TI - Poster 131 Tibial Neuropathy Secondary to Baker Cyst: A Case Report. PMID- 27672900 TI - Poster 135 Sonographic Evaluation of the Achilles and Patellar Tendons in Runners. PMID- 27672901 TI - Poster 133 Analysis of Pain and Functionality in Knee Osteoarthritis Patients after Sodium Hyaluronate Viscosupplementation. PMID- 27672902 TI - Poster 134 Treatment of Chronic Sacroiliac Pain in a Patient with Resolved Pyogenic Sacroiliitis in the Post-Partum State: A Case Report. PMID- 27672903 TI - Poster 136 Meta-Analysis of Non-Operative Modalities in the Treatment of Knee Pain in Osteoarthritis. PMID- 27672904 TI - Poster 137 Delayed Diagnosis of Popliteal Artery Entrapment Mistaken for Exertional Compartment Syndrome, Novel Use of MSK US to Improve Diagnostic Sensitivity: A Case Report. PMID- 27672905 TI - Poster 138 Significant Improvement in Knee Pain in Osteoarthritic Joints After Treatment for Hyperuricemia. PMID- 27672906 TI - Poster 142 Radial Tunnel Syndrome Treated by Ultrasound Guided Perineural Hydrodissection: A Case Report. PMID- 27672907 TI - Poster 139 Severity Correlation Between Cross-Sectional Area and Electrodiagnostic Parameters in Carpal Tunnel Syndrome. PMID- 27672908 TI - Poster 140 Atypical Presentation of Inguinal Hernias in a Golfer: A Case Report. PMID- 27672909 TI - Poster 144 The Effect of Footwear Generated Biomechanical Manipulation on Gait Parameters and Symptoms in a Knee Osteoarthritis Population. PMID- 27672910 TI - Poster 145 Surfer Versus Rock: A Rare Cause of Lower Extremity Weakness and Numbness. PMID- 27672911 TI - Poster 143 Teaching Residents the Loop Threaded Technique for Carpal Tunnel Release: A Preliminary Study. PMID- 27672912 TI - Poster 146 Autoimmune Induced Necrotizing Myopathy. PMID- 27672913 TI - Poster 147 Gender Differences in Symptom Reporting within Student-Athletes from the North Texas Sports Concussion Registry (ConTex). PMID- 27672914 TI - Poster 148 Role of PRP in the Treatment of Knee Osteoarthritis. PMID- 27672915 TI - Poster 149 Diagnosis of an Ulnar Nerve Foreign Body by Ultrasound: A Case Report. PMID- 27672916 TI - Poster 150 Biomechanical Properties of the Glenohumeral Joint Capsule in Adhesive Capsulitis Patients with Diabetes Mellitus. PMID- 27672917 TI - Poster 151 Impairments in Sleep and Anxiety in Patients with Intra-Articular, Non Arthritic Hip Pain. PMID- 27672918 TI - Poster 152 Psychological Status of Recovering Injured Runners: Implications for Rehabilitation Program Content. PMID- 27672919 TI - Poster 155 Higher Cumulative Risk Assessment Scores Are Associated with Delayed Return to Play in Division I Collegiate Distance Runners. PMID- 27672920 TI - Poster 153 Ultrasound Correlated Electrodiagnostic Diagnosis of Neuralgic Amyotrophy in a Collegiate Swimmer After Rapid Practice Intensity Change: A Case Report. PMID- 27672921 TI - Poster 154 Progressive Hip Pain Secondary to Rapidly Destructive Osteoarthritis. PMID- 27672922 TI - Poster 158 New-Onset Gout in a Young Adult Diagnosed Via Sonography: A Case Report. PMID- 27672923 TI - Poster 157 Anatomical Relationship Between the Distal Transverse Carpal Ligament and the Hook of the Hamate: Implications for Ultrasound Guided Carpal Tunnel Release. PMID- 27672924 TI - Poster 156 Synovial Osteochondromatosis as a Rare Cause of Hip Pain: A Case Report. PMID- 27672925 TI - Poster 159 Assessing the Accuracy of Ultrasound Guided Carpometacarpal Joint Injections: A Cadaver Study. PMID- 27672926 TI - Poster 161 Descriptive Study of Injuries in High School Baseball Academy. PMID- 27672927 TI - Poster 160 Transient Unilateral Ptosis in Collegiate Hockey Player Due to Concussion: A Case Report. PMID- 27672928 TI - Poster 164 A Cross-Sectional Survey of Physicians and Registered Massage Therapists Regarding Myofascial Pain Syndrome Diagnostic Criteria. PMID- 27672929 TI - Poster 163 Percutaneous Ultrasonic Tenotomy for Refractory Common Extensor Tendinopathy Following Failed Open Surgical Release: A Case Report. PMID- 27672930 TI - Poster 162 "Dropped Hallux" Following an Open Reduction and Internal Fixation (ORIF) of a Distal Tibia-Fibula Fracture: A Case Report. PMID- 27672932 TI - Poster 166 A Reliability Study of Ultrasound Detection of Myofascial Trigger Points. PMID- 27672931 TI - Poster 167 Ovarian Cyst Rupture as an Unusual Etiology for Hip Pain in a Young Female Runner: A Case Report. PMID- 27672933 TI - Poster 165 Exertional Rhabdomyolysis after Endurance Training. PMID- 27672934 TI - Poster 169 Anticoagulation-Induced Dissecting Hematoma Following Rupture of a Baker's Cyst: A Case Report. PMID- 27672935 TI - Poster 172 Ultrasound Guided Injection of Obturator Internus Bursa: A Case Report. PMID- 27672936 TI - Poster 170 A Rare Case of Radical Mastectomy with Extensive Debridement Due to Necrotizing Fasciitis Leading to Unanticipated Functional Compromise: A Case Report. PMID- 27672937 TI - Poster 171 An Unusual Case of Foot Drop Secondary to Compartment Syndrome: A Case Report. PMID- 27672938 TI - Poster 173 Concussions Presenting with Conversion Disorder: A Case Series. PMID- 27672939 TI - Poster 174 Overlooked Diagnosis of Stress Fractures of the Pubic Ramus. PMID- 27672940 TI - Poster 175 Bilateral Symptomatic Snapping Knee from Biceps Femoris Tendon Subluxation - An Atypical Cause of Bilateral Knee Pain: A Case Report. PMID- 27672941 TI - Poster 178 Motion Alterations in High School and Collegiate Male Lacrosse Players with Chronic Mild Low Back Pain: Implications for Rehabilitation. PMID- 27672942 TI - Poster 177 A Clinical Diagnosis of Athletic Pubalgia: A Case Report. PMID- 27672943 TI - Poster 176 A New Adverse Effect of Glenohumeral Injections: Mechanical Blocking Resulting in Functional Limitations. A Case Report. PMID- 27672944 TI - Poster 181 Botox Application for Recurrent Wrist Pain. PMID- 27672945 TI - Poster 180 Rectus Femoris Avulsion of the Direct and Reflected Heads in a Kickball Player: MRI Diagnosis and Nonoperative Outcome. PMID- 27672946 TI - Poster 179 Ultrasound Guided Percutaneous Tenotomy for Refractory Lateral Epicondylitis. PMID- 27672947 TI - Poster 182 Baseline Characteristics of Cervical Dystonia Subjects in Observational Routine-Practice Studies are Different to Those from Randomized Controlled Trials. PMID- 27672948 TI - Poster 184 Abdominal Muscle Training with Pressure Sensor. PMID- 27672949 TI - Poster 185 Chronic Intractable Calcific Tendinitis of Common Extensor Tendon Successfully Treated with Ultrasound-Guided Barbotage Combined with Extracorporeal Shock Wave Therapy: A Case Report. PMID- 27672950 TI - Poster 188 Quantitative Ultrasound in Patients with Carpal Tunnel Syndrome: A Pilot Study. PMID- 27672951 TI - Poster 187 Is There a Correlation Between Tremor and Other Symptoms of Cervical Dystonia? An Analysis of Data from the Ongoing INTEREST IN CD2 Study. PMID- 27672952 TI - Poster 186 Sonographic Visualization of the Thenar Motor Branch of the Median Nerve: A Cadaveric Validation Study. PMID- 27672953 TI - Poster 190 Utilizing Ultrasound Combined with Electromyography to Provide More Accurate Pre-Surgical Planning: A Case Report. PMID- 27672954 TI - Poster 192 Radial Stress Fracture in a Kettlebell Competitor: A Case Report. PMID- 27672955 TI - Poster 189 Multilevel Spondylolysis in An Adolescent Athlete: A Case Report. PMID- 27672957 TI - Poster 193 Presentation of Humeral Arthritic Marrow Edema Mimicking Carcinoma: A Case Report. PMID- 27672958 TI - Poster 194 Exercise in Non-Vascular Unilateral Amputees and Intact Limb Knee Injury. PMID- 27672959 TI - Poster 197 Unique Presentation of Chronic Hip Pain in a Long Distance Runner: A Case Report. PMID- 27672960 TI - Poster 196 Brain Injury as a Consequence of Routine PRP Protocol in a Patient on Chronic Antiplatelet Therapy. PMID- 27672961 TI - Poster 198 Residual Limb Pain Precipitating Autonomic Dysreflexia in a Traumatic Spinal Cord Injury Patient with Peripheral Artery Disease and Right Above the Knee Amputation: A Case Report. PMID- 27672962 TI - Poster 199 Isolated Cricopharyngeal Dysfunction Following Surgical Resection of a 4th Ventricular Ependymoma: A Case Report. PMID- 27672963 TI - Poster 200 Demyelinating Polyneuropathy Post-Operatively in a Patient with Squamous Cell Carcinoma of the Tongue: A Case Report. PMID- 27672964 TI - Poster 202 A Translational Model of Traumatic Brain Injury: Motor Recovery from a Focal Controlled Cortical Impact to Primary Motor Cortex. PMID- 27672966 TI - Poster 203 Systematic Literature Review of AbobotulinumtoxinA in Randomized, Controlled Clinical Trials for Adult Lower Limb Spasticity. PMID- 27672965 TI - Poster 201 Characterization of Aphasia in Acute Stroke Patients and Correlation with Functional Outcomes. PMID- 27672967 TI - Poster 206 Determinants of Continuous Noninvasive Ventilatory Support Outcomes. PMID- 27672968 TI - Poster 207 Malpositioned Intrathecal Baclofen Pump Catheter Penetrating the Colon: A Case Report. PMID- 27672969 TI - Poster 205 Treatment Characteristics of Post-Stroke Adults Diagnosed with Spasticity Among Commercially and Medicare Insured Populations. PMID- 27672970 TI - Poster 208 Spasticity Diagnosis Rates in Post-Stroke Adult Patients Among Commercially and Medicare Insured Populations. PMID- 27672971 TI - Poster 210 Urine Study Results of Persons with Spinal Cord Injury Presenting for Annual Evaluation. PMID- 27672972 TI - Poster 209 Vocational Outcome 6 to 15 Years after a Traumatic Brain Injury. PMID- 27672973 TI - Poster 212 Functional Improvement through Inpatient Rehabilitation in a Patient with Hyperkinetic Movement Disorder Secondary to Thalamic and Basal Ganglia Stroke: A Case Report. PMID- 27672974 TI - Poster 213 Electromagnetic Interference from Nerve Conduction Studies on a Continuous Glucose Monitor: A Case Report. PMID- 27672975 TI - Poster 211 Heterotopic Ossification Complicating Stroke Recovery in Four Patients: A Case Report. PMID- 27672976 TI - Poster 215 Gustatory Agnosia Following Herpes Simplex Virus Encephalitis: A Case Report. PMID- 27672977 TI - Poster 217 Provider Barriers to Mammography Screening in Women with CP. PMID- 27672978 TI - Poster 218 A Multi-Year Experience with Phenol Neurolysis for Spasticity Management: Practice Pattern and Clinical Outcomes. PMID- 27672979 TI - Poster 222 Acute Onset Diffuse Proximal Muscle Weakness in Setting of Controlled Type 2 Diabetes Mellitus: A Case Report. PMID- 27672980 TI - Poster 221 Pregnancy Termination in a Female with Paraplegia: A Case Report. PMID- 27672981 TI - Poster 219 Carbidopa-Levodopa Improves Speech Apraxia after Hypoxic-Ischemic Brain Injury: A Case Report. PMID- 27672982 TI - Poster 224 Giant Cell Myocarditis Masked by Acute Inflammatory Demyelinating Polyneuropathy: A Case Report. PMID- 27672984 TI - Poster 223 Monomelic Peripheral Neuropathy after Exposure to Cold Weather in a Diplegic Cerebral Palsy. PMID- 27672983 TI - Poster 225 Bickerstaff's Encephalitis with an Exemplary Recovery Following Rehabilitation: A Case Report. PMID- 27672985 TI - Poster 226 Unusual Presentation of Eight and a Half Syndrome in a Patient with Acute Pontine Medullary Stroke: A Case Report. PMID- 27672986 TI - Poster 227 Cauda Equina Syndrome after Lumbar Disk Herniation: A Case Report. PMID- 27672987 TI - Poster 228 Zolpidem for the Treatment of Neurologic Disorders: A Systematic Review. PMID- 27672988 TI - Poster 231 Hemiballismus as the Presenting Symptom of Polycythemia Vera: A Case Report. PMID- 27672989 TI - Poster 230 Unconventional Dosing of Amantadine in a Patient with Traumatic Brain Injury: A Case Report. PMID- 27672990 TI - Poster 229 Athlete with Compression of Thenar Motor Branch and Thumb Digital Branch of Median Nerve: A Case Report. PMID- 27672991 TI - Poster 233 Normal Pressure Hydrocephalus Associated with Toxic Minocycline Findings: A Case Report. PMID- 27672992 TI - Poster 234 Cocaine-Induced Spinal Cord Infarct in a Patient with Copper and Zinc Deficiencies: A Case Report. PMID- 27672993 TI - Poster 232 Cerebral Palsy Adult Transition (CPAT) Cross-Sectional Study Preliminary Findings: Chronic Pain Correlates with Memory Difficulties in Adults with Cerebral Palsy. PMID- 27672994 TI - Poster 236 The Use of a Telepresence Communications Robot by a Patient with Spinal Cord Injury to Aid in Social Reintegration and "Virtual Mobility": A Case Report. PMID- 27672995 TI - Poster 237 Bilateral Hip Fracture During Hospitalization for Spasm Exacerbation in an Adult with Stiff Person Syndrome: A Case Report. PMID- 27672996 TI - Poster 235 Patterns of Intracranial Hemorrhage Based on Traumatic Brain Injury Etiology. PMID- 27672997 TI - Poster 239 Cannabidiol as Treatment for Spasticity: A Case Report. PMID- 27672998 TI - Poster 240 Importance of Recognizing Sinking Skin Flap Syndrome/Syndrome of Trephine: A Case Report. PMID- 27672999 TI - Poster 238 Tumefactive Demyelinating Lesions: Rehabilitation of a Rare, Debilitating Form of Multiple Sclerosis: A Case Report. PMID- 27673000 TI - Poster 243 West Nile Virus Presenting as Paraplegia After Acute Alchohol Withdrawal: A Case Report. PMID- 27673001 TI - Poster 244 An Unusual Cause of Coma from Consumption of Red Yeast Rice: A Case Report. PMID- 27673002 TI - Poster 242 Ultrasound Guided and Doppler Verified Baclofen Pump Refill. PMID- 27673003 TI - Poster 246 Unusual Cause of Myelopathy Related to Neurofibromatosis Type 1: A Case Report. PMID- 27673004 TI - Poster 247 Treatment of Post-Traumatic Chronic Abdominal Pain due to Focal Dystonia with Onabotulinumtoxin A: Two Case Reports. PMID- 27673005 TI - Poster 245 Etiology of Rapid Functional Decline: Myopathy, Neuropathy, or Both? A Case Report. PMID- 27673006 TI - Poster 249 Remarkable Recovery of Function in a Young Adult Female after Low Velocity Penetrating Head Injury and Arrival with Retained Foreign Body: A Case Report. PMID- 27673007 TI - Poster 248 A Novel Infusion Method of Intrathecal Baclofen Using Personal Therapy Manager: A Case Series. PMID- 27673008 TI - Poster 250 Primary Progressive Aphasia a Case Report. PMID- 27673009 TI - Poster 251 Cognitive Decline from Bilateral Deep Brain Stimulator Placement: A Case Report. PMID- 27673010 TI - Poster 252 Use of Fitbit Charge HR for Management of Post-Concussive Syndrome: A Case Report. PMID- 27673011 TI - Poster 253 Implanted Brain-Computer Interface Controlling a Neuroprosthetic for Increasing Upper Limb Function in a Human with Tetraparesis. PMID- 27673012 TI - Poster 257 Tizanidine Reduces Night Sweats due to Dysautonomia in Syringomyelia: A Case Report. PMID- 27673013 TI - Poster 254 A Three Month Journey from the ICU to Return to Work Following Carbon Monoxide Poisoning: A Case Report. PMID- 27673014 TI - Poster 256 Addressing The Downfall of Falls: A Multidisciplinary Approach to Fall Reduction on a Traumatic Brain Injury Rehabilitation Unit. PMID- 27673015 TI - Poster 258 A Novel Approach to the Treatment of Stiff-Person-Syndrome with Botulinum Toxin: A Case Report. PMID- 27673016 TI - Poster 259 Bilateral Corpus Callosum Stroke: Case Review of Neurostimulants to Treat this Patient Population. PMID- 27673017 TI - Poster 260 The Rehabilitative Management of a Patient with Anti-N-methyl-D aspartate Receptor Encephalitis: A Case Report. PMID- 27673018 TI - Poster 261 Treatment of Recurrent Strokes Due to Behcet's Disease with IV Steroids and Inpatient Rehabilitation: A Case Report. PMID- 27673019 TI - Poster 262 Autonomic Dysreflexia Associated with an Arnold Chiari 1 Malformation: A Case Report. PMID- 27673020 TI - Poster 263 The Effect of Pharmacologic Treatment of Depression on Number of Clinician Visits for Persistent Post-Concussion Symptoms in an Adult Population: A Retrospective Review. PMID- 27673021 TI - Poster 264 Migration of Anterior Cervical Fixation Screw Causing both Esophageal and Tracheal Erosive Injuries: Case Report. PMID- 27673022 TI - Poster 265 Relationship Between Severe Headache and Elevated Depression and Anxiety Scores after Sports-Related Concussion. PMID- 27673023 TI - Poster 266 Functional Improvement in a Man with Huntington's Disease After Deep Brain Stimulator Placement in the Globus Pallidus Internus: A Case Report. PMID- 27673024 TI - Poster 267 Intractable Agitation in 33-Year-Old Traumatic Brain Injury Patient due to Trazadone Administration in Acute Inpatient Rehabilitation: A Case Report. PMID- 27673025 TI - Poster 268 Dextromethorphan and Quinidine for Treating Post-Traumatic Brain Injury Agitation: A Case Series. PMID- 27673026 TI - Poster 269 A Rare Case of Femoral Neuropathy Following Anterolateral Total Hip Arthroplasty. PMID- 27673027 TI - Poster 270 Predicting Functional Outcomes in the Severe Traumatic Brain Injury Patient. PMID- 27673028 TI - Poster 272 The Question of Age's Role in Concussion Recovery in Sports: A Retrospective Look at Mixed Martial Arts Fighters and Their First Knockout Loss. PMID- 27673029 TI - Poster 271 Three Dimensional Printing of an Exterior Frontal Bone Cosmetic Prosthesis for a Patient with Frontal Transection Stemming from Traumatic Brain Injury. PMID- 27673031 TI - Poster 274 The Rehabilitation and Recovery of an Adult Survivor of Enterovirus D68 Encephalomyelitis: A Case Report. PMID- 27673030 TI - Poster 275 Acute Encephalopathy in the Setting of Paraplegia Secondary to Metastatic Melanoma to the Lumbar Spine: A Case Report. PMID- 27673032 TI - Poster 273 Botulinum Toxin Injections to the Salivary Glands for Treatment of Sialorrhea in a Patient with Duchenne Muscular Dystrophy: A Case Report. PMID- 27673033 TI - Poster 278 Initial Onset of Acute Migraine Headache Following Diagnosis of Guillain-Barre Syndrome: A Case Report. PMID- 27673034 TI - Poster 277 Maternal Intrathecal Baclofen Therapy Conveys No Added Risk to the Child During Years 0-3: A Case Report. PMID- 27673035 TI - Poster 276 Increased Risk of Bladder Rupture in Non-Compliant SCI Patients with Augmentation Cystoplasty: A Case Report. PMID- 27673036 TI - Poster 279 Radial Neuropathy Exacerbated by Ligamentous Laxity in Pregnancy and by Chemotherapy: A Case Report. PMID- 27673037 TI - Poster 280 ALS Masked by Breast Cancer History and Low Back Pain: A Case Report. PMID- 27673038 TI - Poster 281 The Adult Spasticity International Registry (ASPIRE Study): Baseline Demographics and Clinical Characteristics of Patients Treated for Spasticity. PMID- 27673039 TI - Poster 284 The Effect Playing Electronic Musical Instruments has on the Functional Improvement of the Hemiplegic Upper Limbs and Its Psychological Effect. PMID- 27673040 TI - Poster 283 Improvement in Compensation for Chronic Post-Stroke Homonymous Hemianopsia following Initiation of an SSRI: A Case Report. PMID- 27673041 TI - Poster 282 Functional Gains after Diagnosis of Central Pontine Myelinolysis due to Hypophosphatemia in a Leukemia Patient on an Acute Inpatient Rehabilitation Unit: A Case Report. PMID- 27673042 TI - Poster 286 An Ischemic Stroke and Oral Testosterone Supplementation in a Young Male: A Case Study. PMID- 27673043 TI - Poster 287 Cefepime-Induced Encephalopathy in Acute Rehabilitation Setting: A Case Report. PMID- 27673044 TI - Poster 285 Ultrasound Guided Diaphragmatic EMG in Patient with Respiratory Decline and Pre-Existing Contralateral Diaphragm Atrophy: A Case Report. PMID- 27673045 TI - Poster 290 Efficacy and Safety of a 2 mL Dilution of AbobotulinumtoxinA Compared with Placebo in Adult Patients with Cervical Dystonia. PMID- 27673046 TI - Poster 288 Efficacy and Safety of Repeated AbobotulinumtoxinA Injections in Adults with Lower Limb Spasticity. PMID- 27673047 TI - Poster 289 Patient Registry of Spasticity Care World Data Analysis Based on Physician Experience. PMID- 27673048 TI - Poster 292 Improvement of Spasticity Following AbobotulinumtoxinA (Dysport(r)) Injections in Shoulder Muscles in Hemiparetic Patients with Upper Limb Spasticity Sub-Analysis of a Prospective, Long-Term, Open-Label Study with Single and Repeated Injection Cycles. PMID- 27673049 TI - Poster 293 Pain and Weakness Due to Scurvy and Other Vitamin Deficiencies: A Case Report. PMID- 27673050 TI - Poster 291 Improved Upper Extremity Spasticity During Continuous Intrathecal Baclofen Trial with High Cervical Catheter Placement: A Case Report. PMID- 27673051 TI - Poster 294 Conversion Disorder Rehabilitation: A Case Report. PMID- 27673052 TI - Poster 296 AbobotulinumtoxinA Injection Patterns in Patients with Cervical Dystonia from the ANCHOR-CD Registry Study. PMID- 27673053 TI - Poster 300 Spontaneous Spinal Epidural Hematoma of the Thoracic Spine: A Case Report. PMID- 27673054 TI - Poster 298 Ataxia and Dysarthria in Two Siblings with Kufor-Rakeb Syndrome: A Case Report. PMID- 27673055 TI - Poster 297 Exercise Induced Spinal Cord Infarct (EISCI) in a Young Male with Antiphospholipid Syndrome (APS): A Case Report of a Workman's Compensation (WC) Case Litigation. PMID- 27673056 TI - Poster 299 Pharmacokinetics and Efficacy of Nitroglycerin Paste for Autonomic Dysreflexia Following Spinal Cord Injury. PMID- 27673057 TI - Poster 302 Hemiballism in Middle Cerebral Artery Stroke Improved by Conventional Rehabilitation Therapy: A Case Report. PMID- 27673058 TI - Poster 303 Bladder Distension Associated with Hypotension in a Patient with Tetraplegia after Spinal Cord Injury: A Case Report. PMID- 27673059 TI - Poster 301 Newly Diagnosed Spinal Cord Injury Caused by Vertebra Osteomyelitis in a Patient with Complicated Traumatic Brain Injury: A Case Report. PMID- 27673060 TI - Poster 305 Neural Status of Intact Spinal Cord is a Better Predictor of Surgery Outcome Than Clinical and Imaging Features of Spinal Cord Insult in Cervical Spondylotic Myelopathy: A Case Report. PMID- 27673061 TI - Poster 304 Protracted Course of Inpatient Rehabilitation in a Patient with Severe Acute Demyelinating Polyneuropathy. PMID- 27673062 TI - Poster 306 Rehabilitation of Patients Undergoing Sacrectomies: A Case Report. PMID- 27673063 TI - Poster 308 Improvement of Spasticity, Active Movements and Active Function after Repeated Injections of AbobotulinumtoxinA (Dysport) in Adults with Spastic Paresis in the Upper Limb: Results of a Phase III Open-Label Extension Study. PMID- 27673064 TI - Poster 309 Implementing the Siebens Domain Management Model During Inpatient Rehabilitation to Increase Functional Independence and Discharge Rates to Home from an Inpatient Rehabilitation Facility in Stroke Patients and Minimize Acute Discharges: IRB Approved Study. PMID- 27673065 TI - Poster 310 EMG Guided Botulinum Toxin Type A Injections for Functional Problems Associated to Congenital Facial Palsy: A Case Report. PMID- 27673066 TI - Poster 312 Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients with Post-Stroke Lower-Limb Spasticity Influence Outcome: Results from a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. PMID- 27673067 TI - Poster 313 Relationship Between AbobotulinumtoxinA Injections into Shoulder Muscles and Patient Centred Primary Goal Selection and Achievement: Sub-Analyses from the Upper Limb International Spasticity (ULIS)-II Study. PMID- 27673068 TI - Poster 314 Amyotrophic Lateral Sclerosis Masquerading as Myelopathy: A Case Report. PMID- 27673069 TI - Poster 317 Dose-Related Response to Ultrasound-Guided Ulnar In-Plane Median Nerve Steroid Injections for Carpal Tunnel Syndrome: A Case Report. PMID- 27673070 TI - Poster 316 How a Flexible Differential Yielded an Elusive Diagnosis: A Case Report. PMID- 27673071 TI - Poster 315 Complications Associated with Hajdu-Cheney Syndrome: A Case Report. PMID- 27673072 TI - Poster 319 Response of Postencephalitic Parkinsonism to Various Dopaminergic Agonists: A Case Report. PMID- 27673073 TI - Poster 320 Biopsychosocial Treatment for Functional Neurologic Disorder: A Case Report. PMID- 27673074 TI - Poster 318 Myelopathy in the Setting of a Rare Primary Breast Neoplasm: A Case Report. PMID- 27673075 TI - Poster 322 The Use of Functional Electrical Stimulation in a Neurorehabilitation Unit: A Cross-Sectional Study. PMID- 27673076 TI - Poster 323 Efficacy of Intermittent Dosing of Zolpidem in Disorders of Consciousness: A Case Report. PMID- 27673077 TI - Poster 321 Trazodone Associated Clitoral Priapism in a Transgender Man following Traumatic Brain Injury: A Case Report. PMID- 27673078 TI - Poster 324 Opsoclonus-Myoclonus-Ataxia Syndrome and HIV Infection. A Case Report. PMID- 27673079 TI - Poster 325 A Study on the Swallowing Dynamics During Nasal High-Flow Oxygen Therapy. PMID- 27673080 TI - Poster 326 Paraneoplastic Ovarian Teratoma Anti-NMDA Receptor Encephalitis: A Case Report. PMID- 27673081 TI - Poster 327 The Tribulations, Trials, and Triumphs of Treating and Rehabilitating Hemiballismus: A Case Report. PMID- 27673082 TI - Poster 328 Does Mobility Status or Spasticity Contribute to the Metabolic Profile and Body Composition in Individuals with Cerebral Palsy? PMID- 27673083 TI - Poster 331 Effectiveness of Amantadine in Anoxic Brain Injury: A Case Report. PMID- 27673084 TI - Poster 329 Rehabilitation of Horizontal Diplopia due to Abducens Nerve Palsy in an Idiopathic Pituitary Apoplexy: A Case Report. PMID- 27673085 TI - Poster 330 Rehabilitation of a Patient with Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) Syndrome: A Case Report. PMID- 27673086 TI - Poster 333 Quantitative Electroencephalography in the Evaluation of Concussive Head Injury in Adolescent Children. PMID- 27673087 TI - Poster 334 Treatment of Acute Onset Oromandibular Dystonia in a Patient with Basal Ganglia Hemorrhage: A Case Report. PMID- 27673088 TI - Poster 332 Corticobasal Degeneration with Spastic Left Hemiparesis, Dystonic Posturing, and Rigidity: A Case Report. PMID- 27673089 TI - Poster 338 Rare Case of Hand Weakness and Numbness in an Anoxic Brain Injured Patient: A Case Report. PMID- 27673090 TI - Poster 336 The Paradoxical Improvement of Motor and Speech Function with the Use of Zolpidem (Ambien) in Patients with Anoxic Encephalopathy and TBI. PMID- 27673091 TI - Poster 335 Pulmonary Embolism and Other Challenges Associated with Acute Spinal Cord Injury During Pregnancy. PMID- 27673092 TI - Poster 340 Analysis of Neurosurgical Patients Acutely Discharged (AD) vs Non Acutely Discharged (NAD) from an Inpatient Rehabilitation Facility (IRF). PMID- 27673093 TI - Poster 339 Better Outcome Though Devastating Course: A Case Report. PMID- 27673094 TI - Poster 341 Analysis of Craniotomy Patients with a Complication of Seizures in an Inpatient Rehab Facility. PMID- 27673095 TI - Poster 342 Tethered Cord Syndrome in a Patient with 40-Year History of Spinal Cord Injury: A Case Report. PMID- 27673096 TI - Poster 343 Posterior Circulation Stroke with Secondary Vestibulopathy: A Case Report. PMID- 27673097 TI - Poster 346 Rehabilitation of Progressive Multifocal Leukoencephalopathy: A Case Report. PMID- 27673098 TI - Poster 344 Upper Extremity Weakness Due to Bilateral Brachial Plexopathy from Guillain-Barre Syndrome in a Cancer Patient: A Case Report. PMID- 27673099 TI - Poster 345 Rehabilitation of Bickerstaff Brainstem Encephalitis: A Case Report. PMID- 27673100 TI - Poster 347 Physical Therapy Utilization in the Management of Multiple Sclerosis in the United States. PMID- 27673101 TI - Poster 348 Biospy-Confirmed Neurosarcoidosis Manifesting as a Non-Compressive Myelopathy with Transverse Myelitis and Normal ACE Level: A Case Study. PMID- 27673102 TI - Poster 349 Toxic Encephalopathy and Rash Resulting from Paradichlorobenzene Inhalation: A Case Report. PMID- 27673103 TI - Poster 352 Management of Acute Baclofen Withdrawal in the Setting of Intrathecal Pump Infection: A Case Report. PMID- 27673105 TI - Poster 351 Submersed Treadmill Gait Training in the Acute Inpatient Rehab Setting. PMID- 27673104 TI - Poster 350 Persistent Pneumocephalus After Gun Shot Wound to the Head. PMID- 27673106 TI - Poster 354 OnabotulinumtoxinA to Treat Common Postures in Post-Stroke Lower Limb Spasticity: Identification of a Treatment Paradigm. PMID- 27673107 TI - Poster 353 Acute Onset Chronic Inflammatory Demyelinating Polyneuropathy (A-CIDP) with CNS Involvement Initially Diagnosed as Guillain-Barre Syndrome (GBS): A Case Report. PMID- 27673108 TI - Poster 357 The Correlation of Nutritional Status with Functional Outcome and Falls in Parkinson's Disease. PMID- 27673109 TI - Poster 356 Functional Decline Secondary to Progressive Ataxia, Dizziness and Diplopia: The Increasing Role of the Inpatient Rehabilitation Service in the Evaluation and Management of Undiagnosed Neurologic Conditions: A Case Report. PMID- 27673110 TI - Poster 355 Successful Rehabilitation After Hangman's Fracture and Five Subsequent Cranial Nerve Injuries: A Case Report. PMID- 27673111 TI - Poster 358 Gabapentin Causing Neurologic Dysfunction Leading to Falls. PMID- 27673112 TI - Poster 359 Sensorimotor Polyneuropathy Attributed to Heroin Exposure in Young Female: A Case Report. PMID- 27673113 TI - Poster 360 Acute Rehabilitation of a Patient with Stiff Person Syndrome (SPS) and GAD-Antibody Cerebellar Ataxia: A Case Report. PMID- 27673114 TI - Poster 361 Impact of Early Intervention with OnabotulinumtoxinA Treatment in Adult Patients with Post-Stroke Lower Limb Spasticity. PMID- 27673115 TI - Poster 362 Osmotic Demyelination in Lyme Disease: A Case Report. PMID- 27673116 TI - Poster 363 Primary Lymphoma in Immunocompetent Man Masquerading as CVA: A Case Report. PMID- 27673117 TI - Poster 366 Post-Surgical Rehabilitation of Traumatic Sciatic Nerve Injury Enhanced by Supplemental Beta-Carotene and B-12. PMID- 27673118 TI - Poster 365 Traumatic Brain Injury Resulting from Pontine and Extrapontine Myelinolysis due to Acute Onset of Pregnancy Induced Diabetes Insipidus: A Case Report. PMID- 27673119 TI - Poster 367 Tendon Transfers for Self-Catheterization in a Patient with C6 Sensory Incomplete Tetraplegia: A Case Report. PMID- 27673120 TI - Poster 369 Effect of Wheelchair Games on Employment Status of Disabled Veterans. PMID- 27673121 TI - Poster 370 An International, Observational Study of Botulinum Toxin Type A in Spasticity - SPAsticity in PractiCE (SPACE). PMID- 27673122 TI - Poster 368 An Unusual Presentation of Acute Trismus After Unilateral Basal Ganglia Stroke. PMID- 27673123 TI - Poster 371 Escalating Doses of IncobotulinumtoxinA (400-800U) Are Well Tolerated and Lead to Increasing Improvements in Disability Due to Multifocal Upper- and Lower-Limb Spasticity. PMID- 27673124 TI - Poster 372 Long-Term Intrathecal Baclofen Treatment for Spasticity after Acquired Brain Injury: Does Diagnosis Affect Dosing? PMID- 27673125 TI - Poster 373 Paradoxically Increased Rigidity After Intrathecal Baclofen Injection in a Patient with Multiple Sclerosis: A Case Report. PMID- 27673126 TI - Poster 376 Effects of Anesthetic Fluid Injectates on Lesion Sizes in Cooled Radiofrequency Ablation. PMID- 27673127 TI - Poster 375 Adult Onset Lumbar Radiculopathy Secondary to Type II Diastematomyelia: A Case Report. PMID- 27673128 TI - Poster 374 Sexual Dysfunction After Sacroiliac Joint Radiofrequency Denervation: A Case Report. PMID- 27673129 TI - Poster 379 Paraneoplastic Myelitis Secondary to Hodgkin's Lymphoma: A Case Report. PMID- 27673130 TI - Poster 378 Transverse Myelitis Secondary to Infectious Mononucleosis: A Case Report. PMID- 27673131 TI - Poster 377 The Mystery Case of the Edematous and Painful Foot: Refractory Lower Limb Complex Regional Pain Syndrome (CRPS) in the Setting of Lymphedema in a Patient with Endometrial Cancer and Lynch Syndrome: A Case Report. PMID- 27673132 TI - Poster 380 Immediate Relief After Sacroiliac Joint Injection as a Predictor of Subsequent Relief to Steroid at 2-4 Weeks. PMID- 27673133 TI - Poster 381 Depth Assessment for Cervical Spinal Epidural Injections. PMID- 27673134 TI - Poster 382 Transient Bilateral Hand Paresthesias with Micturition. An Unusual Presentation of Cervical Stenosis: A Case Report. PMID- 27673135 TI - Poster 385 Caudal Epidural Dextrose Injections (D5W) for Chronic Back Pain with Accompanying Buttock or Leg Pain: A Consecutive Patient Study with Long-Term Follow-up. PMID- 27673136 TI - Poster 384 Culture-Negative Osteomyelitis of the Femoral Diaphysis Initially Presenting as Lumbar Radiculopathy in an Otherwise Healthy Individual: A Case Report. PMID- 27673137 TI - Poster 383 Effects of Dextrose Prolotherapy in the Treatment of Patients with Knee Osteoarthritis: A Randomized Controlled Trial. PMID- 27673138 TI - Poster 387 Phantom Pain from Coccygectomy Treated with Chemical Neurolysis. PMID- 27673139 TI - Poster 388 Improvement in Pain Control in Complex Regional Pain Syndrome Treated with Buprenorphine Patch and Topical Compounding Cream Containing Ketamine and Clonidine: A Case Series. PMID- 27673140 TI - Poster 386 Evaluating Personal Factors of Age and Gender within the International Classification of Functioning, Disability, and Health (ICF). PMID- 27673141 TI - Poster 391 Prospective, Double-blind, Randomized Clinical Trial to Compare Single Shot Adductor Canal Nerve Block Versus Femoral Nerve Block Combined with Local Infiltration Analgesia: Postoperative Functional Outcomes After Total Knee Arthroplasty. PMID- 27673142 TI - Poster 389 Is an Integrative Approach Effective in Managing Chronic, Refractory Pain in Veterans? PMID- 27673143 TI - Poster 390 Effect of Atlanto-Axial Joint Injection in Treatment of Cervical Facet Arthropathy: A Case Report. PMID- 27673144 TI - Poster 392 Neurotoxic Manifestations After Intrathecal Gadobutrol Injection: A Case Report. PMID- 27673145 TI - Poster 394 Treatment of Recalcitrant Phantom Limb Pain with Alpha-Stimulation(r): A Case Report. PMID- 27673146 TI - Poster 393 C5 Palsy After Cervical Laminectomy and Fusion: 2 Case Reports. PMID- 27673147 TI - Poster 396 Gabapentin-Induced Myoclonus in Spinal Cord Injury. PMID- 27673148 TI - Poster 395 A Rare Presentation of Severe Cord Compression in a Patient With Multiple Osteochondromatosis: A Case Report. PMID- 27673149 TI - Poster 399 The Bubble Technique: A Novel Use of Sterile Water to Facilitate Lead Placement. PMID- 27673150 TI - Poster 398 Persistent Hiccups Following Epidural Steroid Injection Successfully Treated with Baclofen: A Case Report. PMID- 27673151 TI - Poster 397 Noninvasive Treatment of Cervical Muscle Spasm After Cervical Laminectomy and Fusion: Osteopathic Manipulative Therapy in Acute Rehab: A Case Report. PMID- 27673152 TI - Poster 400 The Role of Onabotulinum Toxin A in a Comprehensive Treatment Approach in a Patient with Complex Regional Pain Syndrome: A Case Report. PMID- 27673153 TI - Poster 401 Optimizing the Process Flow Chart for the Inpatient Management of Osteoporotic Vertebral Compression Fractures (OVCF). PMID- 27673154 TI - Poster 404 The Impact of Ankylosing Spondylitis on Work Productivity in Patients with Paid Work. PMID- 27673155 TI - Poster 402 An Acute Presentation of Spinal Epidural Lipomatosis. PMID- 27673156 TI - Poster 403 Using Item Response Theory to Determine the Ability of the Numeric Rating Scale to Accurately Discriminate Between Levels of Pain Severity in Patients with Radicular or Musculoskeletal Pain. PMID- 27673157 TI - Poster 406 Osteitis Condensans Illi (OCI), A Rare Cause of Low Back Pain: A Case Report. PMID- 27673158 TI - Poster 407 Pain Assessment Survey (PAS) for Assessing Physical Pain in Post Cerebrovascular Accident (CVA) Patients. PMID- 27673159 TI - Poster 405 Prolongation of Botulinum Toxin Effect with Zinc Supplementation: A Case Report. PMID- 27673160 TI - Poster 409 Tackling Pain After Above Knee Amputation: What Are Our Options? A Case Report. PMID- 27673161 TI - Poster 408 Chronic Thoracic Radiculopathy Secondary to Syrinx Responsive to Ultrasound-Guided Transverse Abdominis Plane (TAP) Blockade: A Case Report. PMID- 27673162 TI - Poster 410 Incidence of Patients Testing Positive for Methadone in a Pain Clinic with a Negative Prescription Drug Monitoring Program (PDMP) Report. PMID- 27673163 TI - Poster 411 The Impact of OnabotulinumtoxinA on Severe Headache Days: PREEMPT 24 Week Pooled Analysis. PMID- 27673164 TI - Poster 413 A Case Study Investigating Opioid Medication Utilization in Patients with Complex Regional Pain Syndrome Before and After Ketamine Infusion Therapy. PMID- 27673165 TI - Poster 415 Epidemiology of Naloxone use for Opioid Overdose in a Tertiary Care Medical Center. PMID- 27673166 TI - Poster 412 Estimation of Disability Associated with Fibromyalgia Clinical Features Using Multiple Regression and the SF-36. PMID- 27673168 TI - Poster 416 Dissolution Studies in the Presence of Alcohol with an Abuse Deterrent, Extended-Release Morphine Product Candidate. PMID- 27673167 TI - Poster 417 Tests of the Continuum Theory of Fibromyalgia Using Curve Fitting. PMID- 27673169 TI - Poster 419 Effectiveness of an Interdisciplinary Outpatient Chronic Pain Rehabilitation Program on Veterans Suffering with Chronic Pain. PMID- 27673170 TI - Poster 421 Bony Metastatic Prostate Cancer Imitating Complex Regional Pain Syndrome (CRPS) Type 1: A Case Report. PMID- 27673171 TI - Poster 422 The Body Function, Activity Limitation, and Participation Restriction of Individuals with Chronic Whiplash. PMID- 27673172 TI - Poster 420 Pharmacodynamic Effects from a Category 3 Oral Human Abuse Potential Study of an Abuse-Deterrent, Extended-Release Morphine Product Candidate in Nondependent, Recreational Opioid Users. PMID- 27673173 TI - Poster 424 Diagnostic Injection in Multi-Etiology Painful Shoulder Reduces Harmful Steroid Injection Exposure. PMID- 27673174 TI - Poster 423 An Unusual Case of Postpartum Sacroiliitis: A Case Report. PMID- 27673175 TI - Poster 425 Male Sexual Dysfunction in Patients with Chronic Pain. PMID- 27673176 TI - Poster 426 Comparisons of Functional Pain Relief after Bilateral Synvisc Injections and Genicular Nerve Radiofrequency Ablations: A Case Report. PMID- 27673177 TI - Poster 427 Pharmacodynamic Effects From a Category 3 Intranasal Human Abuse Potential Study of an Abuse-Deterrent, Extended-Release Morphine Product Candidate in Nondependent, Recreational Opioid Users. PMID- 27673178 TI - Poster 430 Hyperhidrosis of the Amputee Patient's Stump and Botulinum Toxin: Multicenter Observational Study. PMID- 27673179 TI - Poster 428 Treating Xiphodynia with Pulsed Radiofrequency Ablation (RFA): A Case Report. PMID- 27673180 TI - Poster 429 Discrepancy Between Electrophysiologic Level and Stenosis Level in Cervical Spondylotic Myelopathy. PMID- 27673181 TI - Poster 431 Anterior Spinal Artery Syndrome Caused by Traumatic Disk Herniation: A Case Report. PMID- 27673182 TI - Poster 435 Paraplegia after Hemodialysis Session: A Case Report. PMID- 27673183 TI - Poster 432 Cauda Equina Compression Secondary to a Rare Form of Metastatic Extra Osseous Myeloma. A Case Report. PMID- 27673184 TI - Poster 434 A Rare Cause of Neck Pain in a 10 Year-Old. PMID- 27673185 TI - Poster 437 Pain in Spinal Cord Injury - An Unusual Presentation of Complex Regional Pain Syndrome: A Case Report. PMID- 27673186 TI - Poster 438 Bamboo Cervical Spine and Neck Pain in a Patient with AA Amyloidosis: A Case Report. PMID- 27673187 TI - Poster 436 Hard to Swallow. Dysphagia Secondary to Cervical Spine Osteophytes: A Case Series. PMID- 27673188 TI - Poster 439 Oral Baclofen for the Treatment of Myalgia-Type Pain in the Setting of Dermatomyositis: A Case Report. PMID- 27673189 TI - Poster 440 Changes in Central Sensitization Associated with Peripheral Joint Injection Do Not Predict Long-Term Pain Relief. PMID- 27673190 TI - Poster 441 Rare Occlusion of a Baclofen Pump Catheter Due to Rotation of Pump in the Abdominal Pocket: A Case Report. PMID- 27673191 TI - Poster 442 Intractable Pelvic Pain Due to Melorheostosis Managed with Spinal Cord Stimulation: A Case Report. PMID- 27673192 TI - Poster 444 Bilateral Lower Extremity Numbness and Weakness Caused by Primary Thoracic Spinal Stenosis: A Case Report. PMID- 27673193 TI - Poster 443 Diving Injury Resulting in a Jefferson Fracture, Vertebral Artery Thrombosis and Brown Sequard Syndrome: A Case Report. PMID- 27673194 TI - Poster 447 Atypical Lumbar Radiculopathy Presentation as Generalized Lower Leg Pain: A Case Report. PMID- 27673195 TI - Poster 445 Retrograde Ejaculation as a Potential Complication with Superior Hypogastric Plexus Blockade Following Ganglion of Impar Neurolysis: A Case Series. PMID- 27673196 TI - Poster 446 A Painful Presentation of a Thoracic Epidural Arachnoid Cyst: A Case Report. PMID- 27673197 TI - Poster 448 Obturator Neuropathy after Lumbar Fusion and Resolution with Ultrasound-Guided Obturator Nerve Block: A Case Report. PMID- 27673198 TI - Poster 450 Addressing Chronic Pain in SCI with Use of Electro-Acupuncture. PMID- 27673199 TI - Poster 451 Schwannoma Presenting as Low Back Pain and Myelopathy: A Case Report. PMID- 27673200 TI - Poster 454 Improving Urine Drug Testing in New Patients at a University Affiliated Pain Clinic and Analysis of Gender Differences in Urine Drug Testing. PMID- 27673202 TI - Poster 453 Correlation of Sacroiliac Joint Injection Response to Outcomes After Minimally Invasive Sacroiliac Joint Fusion. PMID- 27673201 TI - Poster 452 Bipolar Radiofrequency Ablation for the Treatment of Hip Joint Pain Using a Perpendicular Approach: A Case Report. PMID- 27673203 TI - Poster 457 Bioequivalence and Food Effect of a Novel, Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate Compared with a Currently Available Non-AD, ER Morphine Product. PMID- 27673204 TI - Poster 456 Does Provision of Individualized Reports Showing Changes in Pain and Function after Epidural Steroid Injections (ESI) Alter Decision-Making About Future ESI Use? PMID- 27673205 TI - Poster 458 Improvement of Premorbid Developmental Delay Following Treatment of Post Traumatic Hydrocephalus: A Case Report. PMID- 27673206 TI - Poster 459 Missed on Initial Imaging-Rare Head and Neck Injury: A Case Report. PMID- 27673207 TI - Poster 461 Recovery in Acute Inpatient Rehabilitation for Pediatric Anti-N-methyl D-aspartate Receptor Encephalitis: A Case Report. PMID- 27673208 TI - Poster 464 Finicky Eating with Autism Spectrum Disorder, an Explanation for Antalgic Gait: A Case Report. PMID- 27673209 TI - Poster 463 Unexpected Transverse Myelitis after Dinutuximab Therapy for Relapsed Neuroblastoma: A Case Report. PMID- 27673210 TI - Poster 462 Physiatrist Evaluation of Functional Deficits in Pediatric Vascular Malformations: A Retrospective Review. PMID- 27673211 TI - Poster 465 Bilateral Hand Weakness and Atrophy in a Teenager: A Case Report. PMID- 27673212 TI - Poster 466 Inpatient Pain Rehabilitation Outcomes for Adolescents with Chronic Pain and Pain-Associated Disability Secondary to Sickle Cell Disease. PMID- 27673213 TI - Poster 467 Delayed Diagnosis of Cervical Anterior Cord Syndrome in a Child with Combined Traumatic Brain and Spinal Cord Injury: A Case Report. PMID- 27673214 TI - Poster 468 Incidental Finding of Grade IV Cervical Anterolisthesis During Workup for Possible Cerebral Palsy: A Case Report. PMID- 27673216 TI - Poster 472 8-Year-Old Male with Flaccid Quadriplegia After Bone Marrow Transplant: A Case Report. PMID- 27673215 TI - Poster 469 A Variant of Motor Neuron Disorder: Hirayama Disease: A Case Report. PMID- 27673217 TI - Poster 475 Acute Paraplegia Secondary to Spinal Epidural Lipomatosis in a Child with Obesity: A Case Report. PMID- 27673218 TI - Poster 473 Peripheral Nerve Injury in the Setting of Concurrent Anoxic Brain Injury: A Case Report. PMID- 27673219 TI - Poster 474 A Male with Rett Syndrome: Broadening the Differential Diagnosis: A Case Report. PMID- 27673220 TI - Poster 477 Successful Prosthetic Rehabilitation of Fibular Hemimelia without Extensive Surgical Intervention: A Case Report. PMID- 27673221 TI - Poster 478 A Review of the Health-Related Quality of Life in Pediatric Patients with Cerebral Palsy and Associated Spasticity. PMID- 27673222 TI - Poster 476 Chronic Regional Pain Syndrome in a Thirteen-Year-Old Girl Treated with a Peripheral Nerve Catheter and Inpatient Rehabilitation: A Case Report. PMID- 27673223 TI - Poster 479 Economic Burden of Pediatric Spasticity in Cerebral Palsy: A Review of the Literature. PMID- 27673224 TI - Poster 480 Addressing Open Mouth Posture in Children with Cerebral Palsy Through Chemodenervation of the Lateral Pterygoid Muscles: A Case Series of Pediatric Patients. PMID- 27673225 TI - Poster 484 3D Printed Orthotic Designed for Klippel-Feil Syndrome Affected Hypoplastic Thumb: A Case Report. PMID- 27673226 TI - Poster 482 Botulinum Toxin A Injections for Drooling Management in Children. PMID- 27673227 TI - Poster 483 Unsuspected Cause of Pediatric Hip Pain: A Case Report. PMID- 27673228 TI - Poster 487 Chronic Inflammatory Demyelinating Polyneuropathy or Something Else?: A Case Report. PMID- 27673229 TI - Poster 486 Hypothermia in Patients with Baclofen Pumps: A Case Series. PMID- 27673230 TI - Poster 485 Safety and Tolerability of AbobotulinumtoxinA (Dysport) in Children (2 17 Years) with Lower Limb Spasticity Due to Cerebral Palsy: A Pooled Analysis of 8 Clinical Trials. PMID- 27673231 TI - Poster 488 Methylphenidate as a Treatment for Traumatic Brain Injury in a 14 Month-Old Female: A Case Report. PMID- 27673232 TI - Poster 489 Rehabilitation After Pediatric Heart Transplant: A Case Report. PMID- 27673233 TI - Poster 490 Profile of Pediatric Patients with Cerebral Palsy at a Tertiary Hospital Rehabilitation Medicine Department. PMID- 27673234 TI - Poster 494 Unique Characteristics of Patient Handoff in Spinal Cord Injury. PMID- 27673235 TI - Poster 492 The Effect of Tablet PC Based Cognitive Training Program (Injini) for Children with Cognitive Impairment in Educational Field. PMID- 27673236 TI - Poster 491 Mirror Therapy in Improving Hand Function of a Hemiparetic Child with Brain Abscess and Tetralogy of Fallot: A Case Report. PMID- 27673238 TI - Poster 497 Searching for an Oasis in a Physiatry Desert: A Global Survey of the Disability Training and Education Landscape of Healthcare Trainees in West Africa. PMID- 27673237 TI - Poster 496 Budget Impact Analysis of Botulinum Toxin A Therapy for Adult Upper Limb Spasticity in the United States. PMID- 27673240 TI - Poster 500 A Five Year Longitudinal Intervention for Improving Medical Student Exposure to Physical Medicine & Rehabilitation (PM&R). PMID- 27673239 TI - Poster 495 Patient Experience in an Outpatient Pain Clinic: A Plan-Do-Study-Act Quality Improvement Project. PMID- 27673241 TI - Poster 499 A Nationwide Review of Residency Call in Physical Medicine & Rehabilitation. PMID- 27673243 TI - Poster 503 Association Between Functional Assessment of Patients and Their Outcomes: A Systematic Review. PMID- 27673242 TI - Poster 498 Geographic Differences in the Characteristics of Cervical Dystonia Patients. PMID- 27673244 TI - Poster 502 Cost Analysis of Patients with Knee and Back Pain: Potential Implications for Care for patients. PMID- 27673245 TI - Poster 501 Comparing WeeFIM Outcomes in Children with Developmental Disabilities to Children without Developmental Disabilities. PMID- 27673246 TI - Poster 505 Influence of Summer Externship in Physical Medicine & Rehabilitation on Specialty Selection. PMID- 27673247 TI - Poster 506 Immediate Need to Initiate Physical Medicine and Rehabilitation Specialty in Nepal. PMID- 27673248 TI - Poster 504 Single Physician Experience with Improving Patient Satisfaction. PMID- 27673249 TI - Poster 509 U.S. Social Worker Workforce Report Card: Forecasting Nationwide Shortages. PMID- 27673250 TI - Poster 507 Electronic Polling to Measure Resident Education and Work Flow: A Proposed Method. PMID- 27673251 TI - Poster 508 A Pilot Patient Safety Simulation Station for Physical Medicine and Rehabilitation Residents: A Case Report. PMID- 27673252 TI - Poster 511 Evaluating Burnout in Physical Medicine and Rehabilitation Residents. PMID- 27673253 TI - Poster 510 Resident and Faculty Perspectives on Gaps in PM&R Residency Education: A Needs Assessment. PMID- 27673254 TI - Poster 110-A Cognitive Deficits in Patients Admitted to Acute Inpatient Rehabilitation for Recovery from Severe Burn Trauma. PMID- 27673255 TI - Poster 110-B Biomechanical and Functional Benefits of Central Location of Power Wheelchair Drive Controls. PMID- 27673256 TI - Poster 110-C Comparison of Kinesiotaping with Compression Garment in the Treatment of Lymphedema After Breast Cancer: A Preliminary Report. PMID- 27673257 TI - Poster 197-B Prior Ultrasound Training Influences Incorporation of Ultrasound into Outpatient Musculoskeletal Practices. PMID- 27673258 TI - Poster 197-A Hyaluronic Acid Treatment for Osteoarthritis of the Hip with Ultrasound Guidance. PMID- 27673259 TI - Poster 110-D Reducing the Rates of Urinary Tract Infections in Patients with Spinal Cord Injury Using Telehealth Interventions. PMID- 27673260 TI - Poster 110-E A Cause for Concern with Guillain-Barre Syndrome: A Case Report. PMID- 27673261 TI - Poster 197-E Hip Pain Secondary to Intramuscular Lipoma of Tensor Fascia Lata: A Case Report. PMID- 27673262 TI - Poster 197-D Ultrasound-Guided Lidocaine Injection Directs Successful Talus Os Trigonum Resection: A Case Report. PMID- 27673263 TI - Poster 197-C Epidemiology of Cervical Spine Injuries in High School Athletes. PMID- 27673264 TI - Poster 197-F A Comparison of Popliteal Arteries Between Fractured and Sound Legs by Ultrasound in Patients with Femur Fracture. PMID- 27673265 TI - Poster 373-A Immunoglobulin Treatment of Miller Fisher Variant of Acute Demyelinating Inflammatory Polyneuropathy with Underlying Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report. PMID- 27673266 TI - Poster 373-B Demographic and Clinical Features of Children and Adolescents with Spinal Cord Injury: A Turkish Hospital-Based Study. PMID- 27673267 TI - Poster 457-B Complex Regional Pain Syndrome Type 1 in Young Male Adults. PMID- 27673268 TI - Poster 457-A Effect of Pilates Exercise Program on People with Chronic Low Back Pain. PMID- 27673269 TI - Poster 373-C Integrated Upper Limb Spasticity Management Including Botulinum Toxin A (BoNT-A) on Patient-Centered Goal Attainment: Methodology for ULIS-III and Initial Goal-Setting Data. PMID- 27673270 TI - Poster 511-A Spreading the Word: Using Podcasting to Advance Scientific Knowledge Across the Spectrum of PM&R. PMID- 27673271 TI - Poster 457-C Towards Reducing Harms: Designing a Quality Improvement Project to Improve Pain Management and Outcomes Among Chronic Pain and Opioid Users in an Acute Rehabilitation Program. PMID- 27673274 TI - Abstracts From the 48th Congress of the International Society of Paediatric Oncology (SIOP) Dublin, Ireland October 19-22, 2016. PMID- 27673273 TI - Effects of Prefracture Depressive Illness and Postfracture Depressive Symptoms on Physical Performance After Hip Fracture. AB - OBJECTIVES: To compare the effect of prefracture depressive illness and postfracture depressive symptoms on changes in physical performance after hip fracture. DESIGN: Longitudinal observational cohort. SETTING: Baltimore metropolitan area. PARTICIPANTS: Older adults with hip fracture (N = 255). MEASUREMENTS: Prefracture depressive illness (from medical records) at baseline and postfracture depressive symptoms at 2 months (using the Center for Epidemiologic Studies Depression Scale) were measured. Physical performance was measured 2, 6, and 12 months after fracture using the Short Physical Performance Battery (SPPB), a composite metric of functional status with a score ranging from 0 to 12. Weighted estimating equations were used to assess mean SPPB over time, comparing participants with and without prefracture depressive illness and subjects with and without postfracture depressive symptoms. RESULTS: Participants with prefracture depressive illness had an SPPB increase of 0.4 units (95% confidence interval (CI) = -0.5-1.3) from 2 to 6 months, smaller than the increase of 1.0 SPPB unit (95% CI = 0.4-1.6) in those without prefracture depressive illness. Participants with postfracture depressive symptoms had an SPPB increase of 0.2 units (95% CI = -1.0-1.5) from 2 to 12 months, and those without postfracture depressive symptoms had a larger increase of 1.2 units (95% CI = 0.6-1.8) over the same period. Nevertheless, prefracture depressive illness and postfracture depressive symptoms were not significantly associated with SPPB. CONCLUSIONS: Neither prefracture depressive illness nor postfracture depressive symptoms were significantly associated with changes in physical performance after hip fracture, but the magnitude of estimates suggested possible clinically meaningful effects on functional recovery. PMID- 27673272 TI - Environmentally controlled bacterial vesicle-mediated export. AB - Over the past two decades, researchers studying both microbial and host cell communities have gained an appreciation for the ability of bacteria to produce, regulate, and functionally utilize outer membrane vesicles (OMVs) as a means to survive and interact with their cellular and acellular environments. Common ground has emerged, as it appears that vesicle production is an environmentally controlled and specific secretion process; however, it has been challenging to discover the principles that govern fundamentals of vesicle-mediated transport. Namely, there does not appear to be a single mechanism modulating OMV export, nor universal "markers" for OMV cargo incorporation, nor particular host cell responses common to treatment with all OMVs. Given the diversity of species studied, their differences in envelope architecture and composition, the diversity of environmentally regulated bacterial processes, and the variety of interactions between bacteria and their abiotic and biotic environments, this is hardly surprising. Nevertheless, the ability of bacteria to control exported material in the context of a packaged insoluble particle, a vesicle, is emerging as a significant contribution to bacterial viability, biofilm communities, and bacterial-host interactions. In this review, we focus on detailing important, recent findings regarding the content and functional differences in bacterially secreted vesicles that are influenced by growth conditions. PMID- 27673275 TI - Decoupling of excitation and receive coils in pulsed magnetic resonance using sinusoidal magnetic field modulation. AB - In pulsed magnetic resonance, the excitation power is many orders of magnitude larger than that induced by the spin system in the receiving coil or resonator. The receiver must be protected during and immediately after the excitation pulse to allow for the energy stored in the resonator to dissipate to a safe level. The time during which the signal is not detected, the instrumental dead-time, can be shortened by using magnetically decoupled excitation and receive coils. Such coils are oriented, with respect to each other, in a way that minimizes the total magnetic flux produced by one coil in the other. We suggest that magnetically decoupled coils can be isolated to a larger degree by tuning them to separate frequencies. Spins are excited at one frequency, and the echo signal is detected at another. Sinusoidal magnetic field modulation that rapidly changes the Larmor frequency of the spins between the excitation and detection events is used to ensure the resonance conditions for both coils. In this study, the relaxation times of trityl-CD3 were measured in a field-modulated pulsed EPR experiment and compared to results obtained using a standard spin echo method. The excitation and receive coils were tuned to 245 and 256.7MHz, respectively. Using an available rapid-scan, cross-loop EPR resonator, we demonstrated an isolation improvement of approximately 20-30dB due to frequency decoupling. Theoretical analysis, numerical simulations, and proof-of-concept experiments demonstrated that substantial excitation-detection decoupling can be achieved. A pulsed L-band system, including a small volume bi-modal resonator equipped with modulation coils, was constructed to demonstrate fivefold dead-time reduction in comparison with the standard EPR experiment. This was achieved by detuning of the excitation and receive coils by 26MHz and using sinusoidal modulation at 480kHz. PMID- 27673276 TI - Usage of internal magnetic fields to study the early hydration process of cement paste by MGSE method. AB - Internal magnetic field gradients, arising within the porous media due to susceptibility differences at the interfaces of solid and liquid as well as due to the contained magnetic impurities, can be employed by the method of modulated gradient spin echo to get insight into the velocity autocorrelation spectrum of liquid confined in the porous structure. New theoretical treatment of spin interaction with the radio-frequency field and the simultaneously applied static non-uniform magnetic field provides the formula that match well with the measurement of restricted diffusion of water in pores of cement paste. Its fitting to the experimental data gives the changes in the mean size of capillary pores, the spin relaxation and the magnitude of mean internal magnetic field gradients during the induction period and early acceleration stage of hydration processes at different temperatures. PMID- 27673277 TI - Biologically Inspired C-H and C=C Oxidations with Hydrogen Peroxide Catalyzed by Iron Coordination Complexes. AB - The development of catalysts for the selective oxidation of readily available hydrocarbons or organic precursors into oxygenated products is a long-standing goal in organic synthesis. In the last decade, some iron coordination complexes have shown the potential to fit this role. These catalysts can mimic the O-O activation mode of far more sophisticated iron oxygenase enzymes, generating powerful yet selective oxidants. In this review, we report state-of-the-art C-H and C=C oxidations catalyzed by non-heme iron complexes and H2 O2 as the oxidant. Finally, we briefly describe some novel oxidative reactivity and the perspectives of this chemistry. PMID- 27673278 TI - IL-36gamma has proinflammatory effects on human endothelial cells. AB - Interleukin-36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL-36 is now a recognised characteristic of psoriatic skin inflammation. IL-36 is known to induce inflammatory responses in dendritic cells, fibroblasts and epithelial cells. Although vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in skin inflammation, the effects of IL-36 on endothelial cells are unexplored. We here show that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated by IL-36gamma stimulation, and this is reversed by the presence of the endogenous IL-36 receptor antagonist. IL 36gamma-stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T-cells following IL-36gamma stimulation of endothelial cells. These results suggest a role for IL 36gamma in the dermal vascular compartment, and it is likely to enhance psoriatic skin inflammation by activating endothelial cells and promoting leucocyte recruitment. PMID- 27673279 TI - Hyperglycemic Hyperosmolar Status Is Associated with Subsequent All-Cause Mortality in Elderly Adults with Type 2 Diabetes Mellitus. PMID- 27673281 TI - Letter From the Editor: From 2003 to today. PMID- 27673280 TI - Thiotepa-based conditioning for allogeneic stem cell transplantation in acute lymphoblastic leukemia-A survey from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. AB - In this study, we analyzed a thiotepa-based conditioning regimen for allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia, using the EBMT database. A total of 323 patients were identified. The median age was 43 years. Disease status at transplant was first complete remission (CR1) in 48.9%, CR2 in 21.7%, CR3 in 6.2%, while 23.2% of the patients had an active disease at the time of transplant. This was performed from a HLA-matched sibling (49.8%) or a matched-unrelated donor (51.2%). The incidence of acute graft-vs.-host disease (GvHD) (grade > II) was 26.6%, while chronic GvHD occurred in 35.9% of the patients at 1 year (24.6% with extensive disease). With a median follow-up of 16.8 months, the nonrelapse mortality was 12.4 and 25.3% at 100 days and 1 year, respectively. The relapse incidence at 1 year was 33.3% with no difference for patients in CR1 (27%). The one-year leukemia-free survival (LFS) and overall survival (OS) were 57 and 66%, respectively for the entire cohort and 50 and 66%, respectively in patients in CR1. Thiotepa/busulfan +/- melphalan (n = 213) in comparison to thiotepa/other (n = 110) conditioning regimen resulted in higher relapse incidence at 1 year (34.9 vs. 30.3%, P = 0.016) and lower LFS (38.8 vs. 45.9%, P = 0.0203), while nonrelapse mortality (23.8 vs. 26.3%, n.s.) and OS (59.6 vs. 51.1%, P = 0.109) did not differ. This large study suggests that a thiotepa-based conditioning for allogeneic transplantation in acute lymphoblastic leukemia is feasible and effective, with the main outcomes being comparable to those achieved with other regimens. Am. J. Hematol. 92:18-22, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27673282 TI - The importance of dose optimization prior to initiation of a registration trial. PMID- 27673283 TI - Consolidation therapy after autologous stem cell transplant in relapsed/refractory Hodgkin lymphoma. PMID- 27673284 TI - Emerging treatment options for carcinoid syndrome. PMID- 27673285 TI - Special concerns for survivors of prostate cancer. PMID- 27673286 TI - Zika and the safety of the US blood supply. PMID- 27673287 TI - Management of brain metastases in breast cancer. PMID- 27673288 TI - Cytoreductive nephrectomy for metastatic renal cell carcinoma. AB - The incidence of renal cell carcinoma is increasing, with up to one-third of patients presenting with metastatic disease. Combination therapy is used to prolong survival in patients with metastatic renal cell carcinoma, which carries a poor prognosis. Although two pivotal phase 3 trials have demonstrated the efficacy of immunotherapy after cytoreductive nephrectomy for metastatic disease, for now, targeted therapy has replaced immunotherapy as the preferred systemic treatment in these patients. Two ongoing phase 3 trials are evaluating the role of cytoreductive nephrectomy prior to targeted therapy. Proper patient selection is paramount in achieving successful outcomes. PMID- 27673289 TI - The status of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in ovarian cancer, part 2: extending the scope beyond olaparib and BRCA1/2 mutations. AB - Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian cancer, leading both the US Food and Drug Administration (FDA) and the European Medicines Agency to approve olaparib for tumors characterized by BRCA1 and BRCA2 mutations. However, it is becoming increasingly evident that tumors that share molecular features with BRCA-mutant tumors-a concept known as BRCAness-also may exhibit defective homologous recombination DNA repair, and therefore will respond to PARP inhibition. A number of strategies have been proposed to identify BRCAness, including identifying defects in other genes that modulate homologous recombination and characterizing the mutational and transcriptional signatures of BRCAness. In addition to olaparib, a number of other PARP inhibitors are in clinical development. This article reviews the development of PARP inhibitors other than olaparib, and discusses the evidence for PARP inhibitors beyond BRCA1/2-mutant ovarian cancer. PMID- 27673290 TI - The role of high-dose melphalan and autologous stem cell transplant in the rapidly evolving era of modern multiple myeloma therapy. AB - The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma. Emerging evidence from phase 3 studies demonstrates that consolidation therapy with HDM/ASCT further improves depth of response and progression-free survival in the context of modern therapy for multiple myeloma. Moreover, unprecedented survival data from ongoing phase 3 studies of patients treated with modern myeloma therapy followed by HDM/ASCT in first-line or second-line therapy reaffirm single and tandem HDM/ASCT as important standards of care for eligible patients. Herein, we review the evolving role of HDM/ASCT for the treatment of patients with newly diagnosed or relapsed multiple myeloma. PMID- 27673291 TI - Correction: Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma. AB - An article in the July 2016 issue, "Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma" by Gaurav Varma, MSPH, Tyler P. Johnson, MD, and Ranjana H. Advani, MD, described ONO/GS-4059 as a "reversible" inhibitor of BTK when it is in fact an "irreversible" inhibitor. We have made the correction to pages 546 and 552 of the online version at www.hematologyandoncology.net. Many thanks to an astute reader for pointing out the error. This corrects the article pmid:27379948. PMID- 27673294 TI - Sunset on the Sea: John Frederick Kensett. PMID- 27673295 TI - Zika Vaccine Enters Clinical Trials. PMID- 27673296 TI - HHS Funds Development of Faster Zika Diagnostic Test. PMID- 27673297 TI - Final Rules for School Nutrition. PMID- 27673298 TI - Surgery No Benefit to Patients With Meniscal Tears. PMID- 27673299 TI - Simple, Less Expensive Psychotherapy Effective for Depression. PMID- 27673300 TI - Telemonitoring Helps Keep Diabetes Under Control. PMID- 27673301 TI - Heart Health in the Workplace. PMID- 27673302 TI - Opiates Harm Newborns, Too. PMID- 27673303 TI - It's Time to Change the Rules. PMID- 27673304 TI - Endovascular Thrombectomy for Ischemic Stroke: The Second Quantum Leap in Stroke Systems of Care? PMID- 27673305 TI - Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. AB - IMPORTANCE: Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. OBJECTIVE: To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. DESIGN, SETTING, AND PATIENTS: Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. EXPOSURES: Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. RESULTS: Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, -6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, -5.2% [95% CI, -8.3% to -2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, -0.9% to 4.2%]). CONCLUSIONS AND RELEVANCE: In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours. PMID- 27673306 TI - Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. AB - IMPORTANCE: The comparative clinical benefit of nonstatin therapies that reduce low-density lipoprotein cholesterol (LDL-C) remains uncertain. OBJECTIVE: To evaluate the association between lowering LDL-C and relative cardiovascular risk reduction across different statin and nonstatin therapies. DATA SOURCES AND STUDY SELECTION: The MEDLINE and EMBASE databases were searched (1966-July 2016). The key inclusion criteria were that the study was a randomized clinical trial and the reported clinical outcomes included myocardial infarction (MI). Studies were excluded if the duration was less than 6 months or had fewer than 50 clinical events. Studies of 9 different types of LDL-C reduction approaches were included. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted and entered data into standardized data sheets and data were analyzed using meta-regression. MAIN OUTCOMES AND MEASURES: The relative risk (RR) of major vascular events (a composite of cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, or stroke) associated with the absolute reduction in LDL-C level; 5-year rate of major coronary events (coronary death or MI) associated with achieved LDL-C level. RESULTS: A total of 312 175 participants (mean age, 62 years; 24% women; mean baseline LDL-C level of 3.16 mmol/L [122.3 mg/dL]) from 49 trials with 39 645 major vascular events were included. The RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was 0.77 (95% CI, 0.71-0.84; P < .001) for statins and 0.75 (95% CI, 0.66-0.86; P = .002) for established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) (between-group difference, P = .72). For these 5 therapies combined, the RR was 0.77 (95% CI, 0.75-0.79, P < .001) for major vascular events per 1-mmol/L reduction in LDL-C level. For other interventions, the observed RRs vs the expected RRs based on the degree of LDL-C reduction in the trials were 0.94 (95% CI, 0.89-0.99) vs 0.91 (95% CI, 0.90-0.92) for niacin (P = .24); 0.88 (95% CI, 0.83-0.92) vs 0.94 (95% CI, 0.93-0.94) for fibrates (P = .02), which was lower than expected (ie, greater risk reduction); 1.01 (95% CI, 0.94-1.09) vs 0.90 (95% CI, 0.89-0.91) for cholesteryl ester transfer protein inhibitors (P = .002), which was higher than expected (ie, less risk reduction); and 0.49 (95% CI, 0.34-0.71) vs 0.61 (95% CI, 0.58-0.65) for proprotein convertase subtilisin/kexin type 9 inhibitors (P = .25). The achieved absolute LDL-C level was significantly associated with the absolute rate of major coronary events (11 301 events, including coronary death or MI) for primary prevention trials (1.5% lower event rate [95% CI, 0.5%-2.6%] per each 1-mmol/L lower LDL-C level; P = .008) and secondary prevention trials (4.6% lower event rate [95% CI, 2.9%-6.4%] per each 1-mmol/L lower LDL-C level; P < .001). CONCLUSIONS AND RELEVANCE: In this meta-regression analysis, the use of statin and nonstatin therapies that act via upregulation of LDL receptor expression to reduce LDL-C were associated with similar RRs of major vascular events per change in LDL-C. Lower achieved LDL-C levels were associated with lower rates of major coronary events. PMID- 27673307 TI - Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? AB - IMPORTANCE: Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE: To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion. DATA SOURCES AND STUDY SELECTION: Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration. DATA EXTRACTION: Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies. RESULTS: A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95% CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95% CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold <8 mm Hg) was associated with fluid responsiveness (positive LR, 2.6 [95% CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95% CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index >15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95% CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95% CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95% CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95% CI, 0.07-0.22]; pooled sensitivity, 88%). CONCLUSIONS AND RELEVANCE: Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies. PMID- 27673308 TI - Blood Measurement of Carcinoembryonic Antigen Level for Detecting Recurrence of Colorectal Cancer. AB - CLINICAL QUESTION: What is the trade-off between sensitivity and specificity at specific carcinoembryonic antigen (CEA) thresholds for detecting recurrent colorectal cancer? BOTTOM LINE: To detect colorectal cancer recurrence, the sensitivity of CEA ranges from 68% for a threshold of 10 ug/L to 82% for a threshold of 2.5 ug/L and the specificity ranges from 97% for a threshold of 10 ug/L to 80% for a threshold of 2.5 ug/L. PMID- 27673309 TI - Painless Vesicular Eruption on the Dorsal Surfaces of the Hands. PMID- 27673310 TI - Single-blind vs Double-blind Peer Review in the Setting of Author Prestige. PMID- 27673311 TI - Use of Projection Analyses and Obesity Trends. PMID- 27673312 TI - Aspirin and Acute Respiratory Distress Syndrome. PMID- 27673313 TI - Use of Projection Analyses and Obesity Trends-Reply. PMID- 27673314 TI - Emailing Test Results to Patients. PMID- 27673315 TI - Aspirin and Acute Respiratory Distress Syndrome-Reply. PMID- 27673316 TI - Emailing Test Results to Patients-Results. PMID- 27673318 TI - Polluting the Universe. PMID- 27673319 TI - Diagnosis and Treatment of Pancreatic Cystic Neoplasms. PMID- 27673322 TI - So, you've volunteered to lead a project... PMID- 27673323 TI - Synthetic cannabinoid poisoning: A growing health concern. PMID- 27673320 TI - Synaptic reliability and temporal precision are achieved via high quantal content and effective replenishment: auditory brainstem versus hippocampus. AB - KEY POINTS: Auditory brainstem neurons involved in sound source localization are equipped with several morphological and molecular features that enable them to compute interaural level and time differences. As sound source localization works continually, synaptic transmission between these neurons should be reliable and temporally precise, even during sustained periods of high-frequency activity. Using patch-clamp recordings in acute brain slices, we compared synaptic reliability and temporal precision in the seconds-minute range between auditory and two types of hippocampal synapses; the latter are less confronted with temporally precise high-frequency transmission than the auditory ones. We found striking differences in synaptic properties (e.g. continually high quantal content) that allow auditory synapses to reliably release vesicles at much higher rate than their hippocampal counterparts. Thus, they are indefatigable and also in a position to transfer information with exquisite temporal precision and their performance appears to be supported by very efficient replenishment mechanisms. ABSTRACT: At early stations of the auditory pathway, information is encoded by precise signal timing and rate. Auditory synapses must maintain the relative timing of events with submillisecond precision even during sustained and high frequency stimulation. In non-auditory brain regions, e.g. telencephalic ones, synapses are activated at considerably lower frequencies. Central to understanding the heterogeneity of synaptic systems is the elucidation of the physical, chemical and biological factors that determine synapse performance. In this study, we used slice recordings from three synapse types in the mouse auditory brainstem and hippocampus. Whereas the auditory brainstem nuclei experience high-frequency activity in vivo, the hippocampal circuits are activated at much lower frequencies. We challenged the synapses with sustained high-frequency stimulation (up to 200 Hz for 60 s) and found significant performance differences. Our results show that auditory brainstem synapses differ considerably from their hippocampal counterparts in several aspects, namely resistance to synaptic fatigue, low failure rate and exquisite temporal precision. Their high-fidelity performance supports the functional demands and appears to be due to the large size of the readily releasable pool and a high release probability, which together result in a high quantal content. In conjunction with very efficient vesicle replenishment mechanisms, these properties provide extremely rapid and temporally precise signalling required for neuronal communication at early stations of the auditory system, even during sustained activation in the minute range. PMID- 27673325 TI - Sensitive determination of pyrrolizidine alkaloids in Tussilago farfara L. by field-amplified, sample-stacking, sweeping micellar electrokinetic chromatography. AB - Pyrrolizidine alkaloids are the toxic components in Tussilago farfara L. Due to the lack of standard substances for quantitative analysis and traces of pyrrolizidine alkaloids in total alkaloids, the full quality control of Tussilago farfara L has been limited. In this study, we aimed to solve the difficulty of determination of pyrrolizidine alkaloids and identify more components in the total alkaloids. An on-line preconcentration method has been applied to improve determining sensitivity of pyrrolizidine alkaloids in Tussilago farfara L. in which included field-amplified sample stacking and sweeping in micellar electrokinetic capillary chromatography. The main parameters that affected separation and stacking efficiency were investigated in details. Under the optimal conditions, the sensitivity enhancement factors obtained by the developed method for the analytes were from 15- to 12-fold, the limits of detection of senkirkine and senecionine were 2~5 MUg/L. Senkirkine and senecionine have been detected in alkaloids (c) of Tussilago farfara L, along ferulic acid methyl ester and methyl caffeate. The developed method was also applied to the analysis of acid extraction (a) of Tussilago farfara L, and senkirkine could be detected directly. The results indicated that the developed method is feasible for the analysis of pyrrolizidine alkaloids in Tussilago farfara L with good recoveries. PMID- 27673321 TI - While the revolution will not be crystallized, biochemistry reigns supreme. AB - Single-particle cryo-electron microscopy (EM) is currently gaining attention for the ability to calculate structures that reach sub-5 A resolutions; however, the technique is more than just an alternative approach to X-ray crystallography. Molecular machines work via dynamic conformational changes, making structural flexibility the hallmark of function. While the dynamic regions in molecules are essential, they are also the most challenging to structurally characterize. Single-particle EM has the distinct advantage of being able to directly visualize purified molecules without the formation of ordered arrays of molecules locked into identical conformations. Additionally, structures determined using single particle EM can span resolution ranges from very low- to atomic-levels (>30-1.8 A), sometimes even in the same structure. The ability to accommodate various resolutions gives single-particle EM the unique capacity to structurally characterize dynamic regions of biological molecules, thereby contributing essential structural information needed for the development of molecular models that explain function. Further, many important molecular machines are intrinsically dynamic and compositionally heterogeneous. Structures of these complexes may never reach sub-5 A resolutions due to this flexibility required for function. Thus, the biochemical quality of the sample, as well as, the calculation and interpretation of low- to mid-resolution cryo-EM structures (30-8 A) remains critical for generating insights into the architecture of many challenging biological samples that cannot be visualized using alternative techniques. PMID- 27673326 TI - Effect of electrostatic interactions on the ultrafiltration behavior of charged bacterial capsular polysaccharides. AB - Charged polysaccharides are used in the food industry, as cosmetics, and as vaccines. The viscosity, thermodynamics, and hydrodynamic properties of these charged polysaccharides are known to be strongly dependent on the solution ionic strength because of both inter- and intramolecular electrostatic interactions. The goal of this work was to quantitatively describe the effect of these electrostatic interactions on the ultrafiltration behavior of several charged capsular polysaccharides obtained from Streptococcus pneumoniae and used in the production of Pneumococcus vaccines. Ultrafiltration data were obtained using various BiomaxTM polyethersulfone membranes with different nominal molecular weight cutoffs. Polysaccharide transmission decreased with decreasing ionic strength primarily because of the expansion of the charged polysaccharide associated with intramolecular electrostatic repulsion. Data were in good agreement with a simple theoretical model based on solute partitioning in porous membranes, with the effective size of the different polysaccharide serotypes evaluated using size exclusion chromatography at the same ionic conditions. These results provide fundamental insights and practical guidelines for exploiting the effects of electrostatic interactions during the ultrafiltration of charged polysaccharides. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1531-1538, 2016. PMID- 27673327 TI - Roles of HDAC2 and HDAC8 in Cardiac Remodeling in Renovascular Hypertensive Rats and the Effects of Valproic Acid Sodium. AB - Recent studies indicate that histone deacetylases (HDACs) activity is associated with the development and progression of cardiac hypertrophy. In this study, we investigated the effects of a HDACs inhibitor, valproic acid sodium (VPA), on cardiac remodeling and the differential expression of HDACs in left ventricles (LVs) of renovascular hypertensive rats. Renovascular hypertension was induced in rats by the two-kidney two-clip (2K2C) method. Cardiac remodeling, heart function and the differential expression of HDACs were examined at different weeks after 2K2C operation. The effects of VPA on cardiac remodeling, the expressions of HDACs, transforming growth factor-beta 1 (TGF-beta1) and connective tissue growth factor (CTGF) in LV were investigated. The expressions of atrial natriuretic factor, beta-myosin heavy chain, HDAC2 and HDAC8 increased in LV of 2K2C rats at 4, 8, 12 weeks after operation. Cardiac dysfunction, cardiac hypertrophy and fibrosis were markedly attenuated by VPA treatment in 2K2C rats. Further studies revealed that VPA inhibited the expressions of HDAC2, HDAC8, TGF-beta1 and CTGF in LV of 2K2C rats. In summary, these data indicate that HDAC2 and HDAC8 play a key role in cardiac remodeling in renovascular hypertensive rats and that VPA attenuates hypertension and cardiac remodeling. The effect of VPA is possibly exerted via decreasing HDAC2, HDAC8, TGF-beta1 and CTGF expressions in LV of 2K2C rats. PMID- 27673328 TI - Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery. AB - The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues. However, the ECC was selected as a more practical delivery format for both packaging/shipping and vaccine administration ease. We have sought to increase Ty21a acid-resistance to allow for removal from the ECC and immune enhancement. To improve Ty21a acid-resistance, glutamate-dependent acid resistance genes (GAD; responsible for Shigella spp. survival at very low pH) were cloned on a multi copy plasmid (pGad) under a controllable arabinose-inducible promoter. pGad enhanced acid survival of Ty21a by 5 logs after 3 hours at pH 2.5, when cells were pre-grown in arabinose and under conditions that promote an acid-tolerance response (ATR). For genetically 100% stable expression, we inserted the gad genes into the Ty21a chromosome, using a method that allowed for subsequent removal of a selectable antibiotic resistance marker. Further, both bacterial growth curves and survival assays in cultured human monocytes/macrophages suggest that neither the genetic methods employed nor the resulting acid-resistance conferred by expression of the Gad proteins in Ty21a had any effect on the existing attenuation of this vaccine strain. PMID- 27673329 TI - Motor Experience Reprograms Development of a Genetically-Altered Bilateral Corticospinal Motor Circuit. AB - Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can be used as readouts of corticospinal system organization and function and the changes brought about by experience. The Emx1-Cre:EphA4tm2Kldr mouse shares features with the common developmental disorder cerebral palsy: bilateral voluntary motor impairments and bilateral CST miswiring. Emx1-Cre:EphA4tm2Kldr mice with typical motor experiences during development display the bilateral phenotype of "mirror" reaching, because of a strongly bilateral motor cortex motor representation and a bilateral CST. By contrast, Emx1-Cre:EphA4tm2Kldr mice that experienced unilateral forelimb constraint from P1 to P30 and tested at maturity had a more contralateral motor cortex motor representation in each hemisphere; more lateralized CST projections; and substantially more lateralized/independent reaching movements. Changes in CST organization and function in this model can be explained by reduced synaptic competition of the CST from the side without developmental forelimb motor experiences. Using this model we show that unilateral constraint largely abrogated the effects of the genetic mutation on CST projections and thus demonstrates how robust and persistent experience-dependent development can be for the establishment of corticospinal system connections and voluntary control. Further, our findings inform the mechanisms of and strategies for developing behavioral therapies to treat bilateral movement impairments and CST miswiring in cerebral palsy. PMID- 27673330 TI - Long Noncoding RNA miR210HG as a Potential Biomarker for the Diagnosis of Glioma. AB - BACKGROUND: Glioma remains a diagnostic challenge because of its variable clinical presentation and a lack of reliable screening tools. Long noncoding RNAs (lncRNAs) regulate gene function in a wide range of pathophysiological processes and are therefore emerging biomarkers for prostate cancer, hepatic cancer, and other tumor diseases. However, the effective use of lncRNAs as biomarkers for the diagnosis of glioma remains unproven. METHODS: This study included 42 glioma patients and 10 healthy controls. lncRNA and mRNA microarray chips were used to identify dysregulated lncRNAs in tumor tissue and tumor-adjacent normal tissue, and SYBR Green-based miRNA quantitative real-time reverse transcription polymerase chain reactions were used to validate upregulated lncRNAs. A receiver operating characteristic curve analysis was conducted to evaluate the diagnostic accuracy of the lncRNA identified as the candidate biomarker. RESULTS: miR210HG levels were significantly higher in tumor tissue than in tumor-adjacent normal tissue in participating glioma patients. Serum miR210HG levels were also significantly higher in glioma patients than in healthy controls. The receiver operating characteristic curve showed that serum miR210HG was a specific diagnostic predictor of acute pulmonary embolism with an area under the curve of 0.8323 (95% confidence interval, 0.7347 to 0.9299, p < 0.001). CONCLUSION: Our findings indicate that miR210HG could be an important biomarker for the diagnosis of glioma, and, as such, large-scale investigations are urgently needed to pave the way from basic research to clinical use. PMID- 27673331 TI - A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects. AB - The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments. PMID- 27673332 TI - Efficacy of a Cell-Cycle Decoying Killer Adenovirus on 3-D Gelfoam(r) Histoculture and Tumor-Sphere Models of Chemo-Resistant Stomach Carcinomatosis Visualized by FUCCI Imaging. AB - Stomach cancer carcinomatosis peritonitis (SCCP) is a recalcitrant disease. The goal of the present study was to establish an in vitro-in vivo-like imageable model of SCCP to develop cell-cycle-based therapeutics of SCCP. We established 3 D Gelfoam(r) histoculture and tumor-sphere models of SCCP. FUCCI-expressing MKN 45 stomach cancer cells were transferred to express the fluorescence ubiquinized cell-cycle indicator (FUCCI). FUCCI-expressing MKN-45 cells formed spheres on agarose or on Gelfoam(r) grew into tumor-like structures with G0/G1 cancer cells in the center and S/G2 cancer cells located in the surface as indicated by FUCCI imaging when the cells fluoresced red or green, respectively. We treated FUCCI expressing cancer cells forming SCCP tumors in Gelfoam(r) histoculture with OBP 301, cisplatinum (CDDP), or paclitaxel. CDDP or paclitaxel killed only cycling cancer cells and were ineffective against G1/G2 MKN-45 cells in tumors growing on Gelfoam(r). In contrast, the telomerase-dependent adenovirus OBP-301 decoyed the MKN-45 cells in tumors on Gelfoam(r) to cycle from G0/G1 phase to S/G2 phase and reduced their viability. CDDP- or paclitaxel-treated MKN-45 tumors remained quiescent and did not change in size. In contrast, OB-301 reduced the size of the MKN-45 tumors on Gelfoam(r). We examined the cell cycle-related proteins using Western blotting. CDDP increased the expression of p53 and p21 indicating cell cycle arrest. In contrast, OBP-301 decreased the expression of p53 and p21 Furthermore, OBP-301 increased the expression of E2F and pAkt as further indication of cell cycle decoy. This 3-D Gelfoam(r) histoculture and FUCCI imaging are powerful tools to discover effective therapy of SCCP such as OBP-301. PMID- 27673333 TI - Spectroscopic Evidence for Room Temperature Interaction of Molecular Oxygen with Cobalt Porphyrin Linker Sites within a Metal-Organic Framework. AB - Metalloporphyrin-based metal-organic frameworks offer a promising platform for developing solid-state porous materials with accessible, coordinatively unsaturated metal sites. Probing small-molecule interactions at the metalloporphyrin sites within these materials on a molecular level under ambient conditions is crucial for both understanding and ultimately harnessing this functionality for potential catalytic purposes. Co-PCN-222, a metal-organic framework based on cobalt(II) porphyrin linkers. is investigated using in situ UV vis diffuse-reflectance and X-ray absorption spectroscopy. Spectroscopic evidence for the axial interaction of diatomic oxygen with the framework's open metalloporphyrin sites at room temperature is presented and discussed. PMID- 27673334 TI - Insights into the Three-Dimensional Structure of Amorpha-4,11-diene Synthase and Probing of Plasticity Residues. AB - Amorphadiene synthase (ADS) is known for its vital role as a key enzyme in the biosynthesis of the antimalarial drug artemisinin. Despite the vast research targeting this enzyme, an X-ray crystal structure of the enzyme has not yet been reported. In spite of the remarkable difference in product profile among various sesquiterpene synthases, they all share a common alpha-helical fold with many highly conserved regions especially the bivalent metal ion binding motifs. Hence, to better understand the structural basis of the mechanism of ADS, a reliable 3D homology model representing the conformation of the ADS enzyme and the position of its substrate, farnesyl diphosphate, in the active site was constructed. The model was generated using the reported crystal structure of alpha-bisabolol synthase mutant, an enzyme with high sequence identity with ADS, as a template. Site-directed mutagenesis was used to probe the active site residues. Seven residues were probed showing their vital role in the ADS mechanism and/or their effect on product profile. The generated variants confirmed the validity of the ADS model. This model will serve as a basis for exploring structure-function relationships of all residues in the active site to obtain further insight into the ADS mechanism. PMID- 27673335 TI - Synthesis of Double-Shell SnO2@C Hollow Nanospheres as Sulfur/Sulfide Cages for Lithium-Sulfur Batteries. AB - Double-shell SnO2@C hollow nanospheres were synthesized by a template method, and then the sulfur was loaded to form a cathode material of S/SnO2@C composite. In Li-S batteries, it delivered a high initial specific capacity of 1473.1 mAh/g at a current density of 200 mA/g, and the capacity retention was even up to 95.7% over 100 cycles at 3200 mA/g, i.e., a capacity fade rate of only 0.043% per cycle. These good electrochemical performances should be attributed to the SnO2@C hollow nanospheres. They can enhance the electronic conductivity by the outside carbon shell, and confine the lithium polysulfides by S-Sn-O and S-C chemical bonds to suppress the shuttle effect. Besides, the hollow nanospheres can readily accommodate the sulfur/sulfides to prevent the electrical/mechanical failure of the cathode, instead of their agglomeration on the external surface of SnO2@C. PMID- 27673336 TI - Redox Active Polymers as Soluble Nanomaterials for Energy Storage. AB - It is an exciting time for exploring the synergism between the chemical and dimensional properties of redox nanomaterials for addressing the manifold performance demands faced by energy storage technologies. The call for widespread adoption of alternative energy sources requires the combination of emerging chemical concepts with redesigned battery formats. Our groups are interested in the development and implementation of a new strategy for nonaqueous flow batteries (NRFBs) for grid energy storage. Our motivation is to solve major challenges in NRFBs, such as the lack of membranes that simultaneously allow fast ion transport while minimizing redox active species crossover between anolyte (negative electrolyte) and catholyte (positive electrolyte) compartments. This pervasive crossover leads to deleterious capacity fade and materials underutilization. In this Account, we highlight redox active polymers (RAPs) and related polymer colloids as soluble nanoscopic energy storing units that enable the simple but powerful size-exclusion concept for NRFBs. Crossover of the redox component is suppressed by matching high molecular weight RAPs with simple and inexpensive nanoporous commercial separators. In contrast to the vast literature on the redox chemistry of electrode-confined polymer films, studies on the electrochemistry of solubilized RAPs are incipient. This is due in part to challenges in finding suitable solvents that enable systematic studies on high polymers. Here, viologen-, ferrocene- and nitrostyrene-based polymers in various formats exhibit properties that make amenable their electrochemical exploration as solution-phase redox couples. A main finding is that RAP solutions store energy efficiently and reversibly while offering chemical modularity and size versatility. Beyond the practicality toward their use in NRFBs, the fundamental electrochemistry exhibited by RAPs is fascinating, showing clear distinctions in behavior from that of small molecules. Whereas RAPs conveniently translate the redox properties of small molecules into a nanostructure, they give rise to charge transfer mechanisms and electrolyte interactions that elicit distinct electrochemical responses. To understand how the electrochemical characteristics of RAPs depend on molecular features, including redox moiety, macromolecular size, and backbone structure, a range of techniques has been employed by our groups, including voltammetry at macro- and microelectrodes, rotating disk electrode voltammetry, bulk electrolysis, and scanning electrochemical microscopy. RAPs rely on three-dimensional charge transfer within their inner bulk, which is an efficient process and allows quantitative electrolysis of particles of up to ~800 nm in radius. Interestingly, we find that interactions between neighboring pendants create unique opportunities for fine-tuning their electrochemical reactivity. Furthermore, RAP interrogation toward the single particle limit promises to shed light on fundamental charge storage mechanisms. PMID- 27673337 TI - Plant Cell Wall-Penetrable, Redox-Responsive Silica Nanoprobe for the Imaging of Starvation-Induced Vesicle Trafficking. AB - Autophagy is a self-protection process against reactive oxygen species (ROS). The intracellular level of ROS increased when cells were cultured under nutrient starvation. Antioxidants such as glutathione and ascorbic acid play an important role in ROS removal. However, the cellular redox state in the autophagic pathway is still unclear. Herein, we developed a new redox-sensitive probe with a disulfide-linked silica scaffold to enable the sensing of the reduction environment in cell organelles. This redox-responsive silica nanoprobe (ReSiN) could penetrate the plant cell wall and release fluorescent molecules in response to redox states. By applying the ReSiN to tobacco BY-2 cells and tracing the distribution of fluorescence, we found a higher reducing potential in the central vacuole than in the autolysosomes. Upon cysteine protease inhibitor (E64-c) treatment in sucrose-free medium, the disulfide-silica structures of the ReSiNs were broken down in the vacuoles but were not degraded and were accumulated in the autolysosomes. These results reveal the feasibility of our nanoprobe for monitoring the endocytic and macroautophagic pathways. These pathways merge upstream of the central vacuole, which is the final destination of both pathways. In addition, different redox potentials were observed in the autophagic pathway. Finally, the expression of the autophagy-related protein (Atg8) fused with green fluorescence protein confirmed that the ReSiN treatment itself did not induce the autophagic pathway under normal physiological conditions, indicating the versatility of this nanoprobe in studying stimuli-triggered autophagy-related trafficking. PMID- 27673338 TI - Low-Temperature Growth of Indium Oxide Thin Film by Plasma-Enhanced Atomic Layer Deposition Using Liquid Dimethyl(N-ethoxy-2,2-dimethylpropanamido)indium for High Mobility Thin Film Transistor Application. AB - Low-temperature growth of In2O3 films was demonstrated at 70-250 degrees C by plasma-enhanced atomic layer deposition (PEALD) using a newly synthesized liquid indium precursor, dimethyl(N-ethoxy-2,2-dimethylcarboxylicpropanamide)indium (Me2In(EDPA)), and O2 plasma for application to high-mobility thin film transistors. Self-limiting In2O3 PEALD growth was observed with a saturated growth rate of approximately 0.053 nm/cycle in an ALD temperature window of 90 180 degrees C. As-deposited In2O3 films showed negligible residual impurity, film densities as high as 6.64-7.16 g/cm3, smooth surface morphology with a root mean-square (RMS) roughness of approximately 0.2 nm, and semiconducting level carrier concentrations of 1017-1018 cm-3. Ultrathin In2O3 channel-based thin film transistors (TFTs) were fabricated in a coplanar bottom gate structure, and their electrical performances were evaluated. Because of the excellent quality of In2O3 films, superior electronic switching performances were achieved with high field effect mobilities of 28-30 and 16-19 cm2/V.s in the linear and saturation regimes, respectively. Furthermore, the fabricated TFTs showed excellent gate control characteristics in terms of subthreshold swing, hysteresis, and on/off current ratio. The low-temperature PEALD process for high-quality In2O3 films using the developed novel In precursor can be widely used in a variety of applications such as microelectronics, displays, energy devices, and sensors, especially at temperatures compatible with organic substrates. PMID- 27673339 TI - Nonlinear-Optical Response of Prussian Blue: Strong Three-Photon Absorption in the IR Region. AB - The nonlinear-optical properties of Prussian Blue nanoparticles have been evaluated with the use of femtosecond Z-scan measurements in the 1350-1750 nm range. This well-known inorganic pigment having interesting magnetic and electrochemical properties was found to be an efficient near-IR three-photon absorber. The maximum of the effective three-photon cross section is as high as 4.5 * 10-78 cm6 s2 at 1375 nm. By a comparison of the three-photon molar-mass normalized merit factors, sigma3/M, we show that this material is a competitive multiphoton absorber, especially in comparison to semiconductor quantum dots. PMID- 27673340 TI - Role of Asn112 in a Light-Driven Sodium Ion-Pumping Rhodopsin. AB - Light-driven outward sodium-pumping rhodopsin (NaR) was recently found in marine bacteria. Krokinobacter eikastus rhodopsin 2 (KR2) actively transports sodium and lithium ions in NaCl and LiCl, respectively, while it pumps protons in KCl. NaR has a conserved NDQ (N112, D116, and Q123 in KR2) motif, and previous studies suggested an important role for N112 in the function of KR2. Here we replaced N112 with 19 different amino acids and studied the molecular properties of the mutants. All mutants exhibited absorption bands from a protonated Schiff base in the lambdamax range from 508 to 531 nm upon heterologous expression in Escherichia coli, whose ion-pumping activity was measured using pH electrodes. The function of these mutants was classified into three phenotypes: wild-type (WT)-like Na+/H+ compatible pump, exclusive H+ pump, and no pump. Among the 19 mutants, only N112D, -G, -S, and -T showed light-driven Na+ pump activity, N112A, -C, -P, -V, -E, -Q, -I, -L, -M, -F, and -W were exclusively H+ pumps, and N112H, K, -Y, and -R exhibited no pump activity. The mutants of the no pump function lack a blue-shifted M intermediate, indicating that Schiff base deprotonation is a prerequisite for Na+ and H+ pumps. In contrast, the subsequent red-shifted O intermediate was observed for WT and N112V but absent for N112T and N112A, suggesting that observation of this intermediate depends on kinetics. Although N112D, -G, -S, and -T are able to pump Na+, they also pump H+ in NaCl, where Na+ and H+ pumps compete with each other because of the decreased Na+ uptake efficiency. From these facts, an exclusive Na+ pump in NaCl exists only in WT. We conclude that N112 is one of the functional determinants of NaR. PMID- 27673341 TI - Heterogeneous Photocatalytic Click Chemistry. AB - Copper-doped semiconductors are designed to photoassist the alkyne-azide cycloaddition catalysis by Cu(I). Upon irradiation, injection of electrons from the semiconductor into copper oxide nanostructures produces the catalytic Cu(I) species. The new catalysts are air- and moisture-tolerant and can be readily recovered after use and reused several times. PMID- 27673342 TI - Spontaneous Formation of Atomically Thin Stripes in Transition Metal Dichalcogenide Monolayers. AB - Whether an alloy is random or ordered can have profound effects on its properties. The close chemical similarity of W and Mo in the two-dimensional semiconductors MoS2 and WS2 has led to the expectation that WxMo1-xS2 is a random alloy. Here we report that triangular monolayer flakes of WxMo1-xS2 produced by sulfurization of MoO3/WO3 are not only nonrandom, but also anisotropic: W and Mo form atomically thin chains oriented parallel to the edges of the triangle, especially around x ~ 0.5, as resolved by aberration-corrected transmission electron microscopy. First-principles calculations reveal that the binding energies of striped and random alloys are nearly identical but that phase segregation at the growth edge favors one metal over another depending on the local sulfur availability, independent of the composition deeper inside the monolayer. Thus, atomically thin striping is kinetically driven and controlled by fluctuations that couple the local chemical potentials of metals and chalcogenide. Considering the nearly identical electronic properties but very different atomic masses of Mo and W, the resulting striped alloy is electronically isotropic, but vibrationally anisotropic. Phonon anomalies associated with the stripe ordering are predicted, as is an anisotropic thermal conductivity. More generally, fluctuation-driven striping provides a mechanism to produce in-plane subnanometer superlattices within two-dimensional crystals, with broad implications for controlling the electronic, optical, and structural properties of these systems. PMID- 27673344 TI - Electron-Beam Lithographic Grafting of Functional Polymer Structures from Fluoropolymer Substrates. AB - Well-defined submicrometer structures of poly(dimethylaminoethyl methacrylate) (PDMAEMA) were grafted from 100 MUm thick films of poly(ethene-alt tetrafluoroethene) after electron-beam lithographic exposure. To explore the possibilities and limits of the method under different exposure conditions, two different acceleration voltages (2.5 and 100 keV) were employed. First, the influence of electron energy and dose on the extent of grafting and on the structure's morphology was determined via atomic force microscopy. The surface grafting with PDMAEMA was confirmed by advanced surface analytical techniques such as time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy. Additionally, the possibility of effective postpolymerization modification of grafted structures was demonstrated by quaternization of the grafted PDMAEMA to the polycationic QPDMAEMA form and by exploiting electrostatic interactions to bind charged organic dyes and functional proteins. PMID- 27673343 TI - Antiviral Spirotriscoumarins A and B: Two Pairs of Oligomeric Coumarin Enantiomers with a Spirodienone-Sesquiterpene Skeleton from Toddalia asiatica. AB - Two pairs of oligomeric coumarin enantiomers, spirotriscoumarin A [(+)-1 and (-) 1] and spirotriscoumarin B [(+)-2 and (-)-2], with a spirodienone-sesquiterpene fused skeleton were isolated from Toddalia asiatica. Their structures were unambiguously established using spectroscopic data, X-ray diffraction analysis, and the electronic circular dichroism (ECD) method. The racemic mixtures (+/-)-1 and (+/-)-2 exhibit 3-to-6-fold stronger antiviral activity against influenza virus A (H3N2) (IC50: 3.13 and 2.87 MUM, respectively) than their corresponding optically pure enantiomers. PMID- 27673345 TI - Early Physiotherapy by Passive Range of Motion Does Not Affect Partial Brain Tissue Oxygenation in Neurocritical Care Patients. AB - Background Studies investigating multimodal cerebral monitoring including partial brain tissue oxygen monitoring (ptiO2) in neuro-intensive care patients during physiotherapy are completely lacking in the literature. Materials and Methods We performed a post hoc analysis of prospectively collected data of patients on multimodal cerebral monitoring by intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurement as well as ptiO2. Patients with severe brain diseases were treated with passive range of motion (PROM). We recorded ICP, CPP, and ptiO2 continuously every minute at baseline (15 minutes), during treatment (26 minutes), and 15 minutes after treatment with PROM. Results Overall, 25 treatment units with PROM in 10 patients with combined ICP/CPP and ptiO2 monitoring were evaluated. Median ICP, CPP, and ptiO2 at baseline were 12 +/- 6.1 mm Hg, 86 +/- 17.1 mm Hg, and 27 +/- 14.3 mm Hg, respectively. Values for ICP, CPP, and ptiO2 did not change significantly when comparing mean values before, during, and after therapy. Conclusions Based on ptiO2 measurements, our data provide new information about the feasibility and safety of physiotherapy in patients with severe brain diseases. PMID- 27673346 TI - The alternative strategy for designing covalent drugs through kinetic effects of pi-stacking on the self-assembled nanoparticles: a model study with antibiotics. AB - It is still a huge challenge to find a new strategy for rationally designing covalent drugs because most of them are discovered by serendipity. Considering that the effect of covalent drugs is closely associated with the kinetics of the reaction between drug molecule and its target protein, here we first demonstrate an example of the kinetic effect of pi-stacking of drug molecules on covalent antimicrobial drug design. When PEGylated 7-aminocephalosporanic acid (PEG-ACA) is used as a substrate drug, pi-stacking of the ACA group via the self-assembly of PEG-ACA on the surface of gold nanoparticles (i.e. Au@ACA) exhibits antibacterial activity against E. coli fourfold higher than a PEG-ACA monomer does. The reason can be reasonably attributed to the kinetic rate enhancement for the covalent reaction between Au@ACA and penicillin binding proteins. We believe that the self-assembly of functional groups onto the surface of gold nanoparticles represents a new strategy for covalent drug design. PMID- 27673347 TI - A Rapid and Efficient Method of Identifying G0 Males with Mosaic Germ Line Cells. PMID- 27673348 TI - Yr58: A New Stripe Rust Resistance Gene and Its Interaction with Yr46 for Enhanced Resistance. AB - The quantitative trait loci QYr.sun-3BS and QYr.sun-4DL were identified in the W195/BTSS recombinant inbred line (RIL) population in a previous study. QYr.sun 3BS explained 34 to 59% phenotypic variation in stripe rust response. We evaluated parental genotypes at different growth stages and temperature regimes to detect the critical stage for expression of QYr.sun-3BS. W195 expressed low infection type (IT) ;1C at the fourth leaf stage, when incubated at 21 +/- 2 degrees C and the alternate parent BTSS was susceptible (IT 3+). Monogenic segregation for stripe rust response was observed among the RIL population at the fourth leaf stage and the underlying locus was temporarily named YrW195. YrW195 corresponded to QYr.sun-3BS. Since no previously designated stripe rust resistance genes that expresses at and after the fourth leaf stage was mapped in this region, YrW195 was formally named Yr58. Genotyping with Yr46-linked markers indicated the presence of Yr46 in W195, which corresponded to QYr.sun-4DL. The RILs carrying Yr58 and Yr46 singly produced IT 23C and IT 3+, respectively, and those carrying both genes produced IT ;1C indicating the enhancement of Yr58 expression by Yr46. The absence of Yr58-linked alleles of markers sun533 and sun476 in 74 of the 76 wheat cultivars demonstrated their usefulness for marker assisted selection. PMID- 27673351 TI - The role of clinical experience, diagnosis, and theoretical orientation in the treatment of posttraumatic and dissociative disorders: A vignette and survey investigation. AB - Controversy exists regarding the merits of exposure-based treatments for posttraumatic stress disorder (PTSD) versus a phased approach when prominent dissociative symptoms are present. The first aim of this study was to examine the degree to which diagnosing dissociation in two traumatized patients' vignettes influenced clinicians' preference for phase-oriented treatment and whether clinicians' treatment experience contributed to their treatment preference. The second aim was to assess the extent to which participants had observed traumatized patients worsen when treated with exposure therapy or phase-oriented therapy and whether the theoretical orientation and treatment experience of the clinician were related to the observed deterioration. In the tradition of expert and practitioner surveys, 263 clinicians completed a survey of their diagnoses and treatment preferences for two vignettes and their treatment experience, theoretical orientation, and observations of patients' deterioration. When a marked degree of dissociation was noted in the PTSD vignette, respondents favored phased approaches regardless of the diagnosis given. Reports of having observed patient deterioration during both exposure and phased therapy were predicted by years of experience. Psychodynamic therapists reported more observations of worsening during exposure therapy than cognitive behavior therapy therapists. Clinical experience treating PTSD may heighten awareness of negative therapeutic effects, potentially because experienced clinicians have a lower threshold for detecting such effects and because they are referred more challenging cases. PMID- 27673352 TI - Impact of the Omnipod(r) Insulin Management System on Quality of Life: A Survey of Current Users. AB - BACKGROUND: Few recent studies have examined the impact of continuous subcutaneous insulin infusion systems on patient-reported quality of life (QOL). We explored QOL changes resulting from treatment with the Omnipod(r) Insulin Management System (Insulet Corp., Billerica, MA). METHODS: One thousand two hundred forty-five adults (>18 years) with type 1 diabetes and current Omnipod users completed an online questionnaire examining perceived changes in QOL and glycemic control since Omnipod initiation. The QOL dimensions included overall well-being (World Health Organization-5, modified to examine changes retrospectively), diabetes distress (Type 1 Diabetes Distress Scale, current distress and a modified retrospective version), and psychosocial impact (two subscales from the Diabetes Technology Impact Measure, perceived control over diabetes, and hypoglycemic safety). Regression analyses examined associations between demographics, key psychological factors, and perceived change in glycemic control with the QOL dimensions. RESULTS: Broad QOL and clinical benefits associated with Omnipod use were common. The majority reported positive changes in the following: overall well-being (53.5%), perceived control over diabetes (72.5%), hypoglycemic safety (50.6%), and diabetes distress (69.6%). Worsening in any of these areas was uncommon. In addition, 64.2% of patients reported glycemic improvement post-Omnipod initiation, while 35.2% reported a decrease in severe hypoglycemic episodes. Trust in one's Omnipod, perceived improvement in glycemic control, and reductions in severe hypoglycemia independently predicted benefits in all QOL measures (all P < 0.001). CONCLUSIONS: These findings suggest that Omnipod users perceived substantial QOL benefits from the device; benefits are more apparent in those who trust the device and have noted positive changes in glycemic control. PMID- 27673353 TI - Roles and Signaling Pathways of Des-gamma-Carboxyprothrombin in the Progression of Hepatocellular Carcinoma. AB - Des-gamma-carboxyprothrombin (DCP), an abnormal prothrombin produced in human hepatocellular carcinoma (HCC), plays crucial roles in the progression of HCC. DCP binding to cellular mesenchymal-epithelial transition factor (c-Met) is an initial event and consequently stimulates HCC through the increase of c-Met-Janus kinase 1- signal transducers and activators of transcription pathways. DCP stimulates HCC invasion through activation of matrix metalloproteinase via upregulation of extracellular signal-regulated kinase-mitogen-activated protein kinase (MAPK) pathway. DCP stimulates HCC angiogenesis through activation of the DCP-kinase insert domain receptor-phospholipaseC-gamma-MAPK pathway. Identification of these pathways is important for designing the therapeutic strategy for HCC. PMID- 27673355 TI - Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair. AB - The nucleolus represents a highly multifunctional intranuclear organelle in which, in addition to the canonical ribosome assembly, numerous processes such as transcription, DNA repair and replication, the cell cycle, and apoptosis are coordinated. The nucleolus is further a key hub in the sensing of cellular stress and undergoes major structural and compositional changes in response to cellular perturbations. Numerous nucleolar proteins have been identified that, upon sensing nucleolar stress, deploy additional, non-ribosomal roles in the regulation of varied cell processes including cell cycle arrest, arrest of DNA replication, induction of DNA repair, and apoptosis, among others. The highly abundant proteins nucleophosmin (NPM1) and nucleolin (NCL) are two such factors that transit to the nucleoplasm in response to stress, and participate directly in the repair of numerous different DNA damages. This review discusses the contributions made by NCL and (or) NPM1 to the different DNA repair pathways employed by mammalian cells to repair DNA insults, and examines the implications of such activities for the regulation, pathogenesis, and therapeutic targeting of NPM1 and NCL. PMID- 27673356 TI - Ultrasound for In Vitro, Noninvasive Real-Time Monitoring and Evaluation of Tissue-Engineered Heart Valves. AB - Tissue-engineered heart valves are developed in bioreactors where biochemical and mechanical stimuli are provided for extracellular matrix formation. During this phase, the monitoring possibilities are limited by the need to maintain the sterility and integrity of the valve. Therefore, noninvasive and nondestructive techniques are required. As such, optical imaging is commonly used to verify valve's functionality in vitro. It provides important information (i.e., leaflet symmetry, geometric orifice area, and closing and opening times), which is, however, usually limited to a singular view along the central axis from the outflow side. In this study, we propose ultrasound as a monitoring method that, in contrast to established optical imaging, can assess the valve from different planes, scanning the whole three-dimensional geometry. We show the potential benefits associated with the application of ultrasound to bioreactors, in advancing heart valve tissue engineering from design to fabrication and in vitro maturation. Specifically, we demonstrate that additional information, otherwise unavailable, can be gained to evaluate the valve's functionality (e.g., coaptation length, and effective cusp height and shape). Furthermore, we show that Doppler techniques provide qualitative visualization and quantitative evaluation of the flow through the valve, in real time and throughout the whole in vitro fabrication phase. PMID- 27673354 TI - Pomegranate Intake Protects Against Genomic Instability Induced by Medical X-rays In Vivo in Mice. AB - Ionizing radiation (IR) is a well-documented human carcinogen. The increased use of IR in medical procedures has doubled the annual radiation dose and may increase cancer risk. Genomic instability is an intermediate lesion in IR-induced cancer. We examined whether pomegranate extract (PE) suppresses genomic instability induced by x-rays. Mice were treated orally with PE and exposed to an x-ray dose of 2 Gy. PE intake suppressed x-ray-induced DNA double-strand breaks (DSBs) in peripheral blood and chromosomal damage in bone marrow. We hypothesized that PE-mediated protection against x-ray-induced damage may be due to the upregulation of DSB repair and antioxidant enzymes and/or increase in glutathione (GSH) levels. We found that expression of DSB repair genes was not altered (Nbs1 and Rad50) or was reduced (Mre11, DNA-PKcs, Ku80, Rad51, Rad52 and Brca2) in the liver of PE-treated mice. Likewise, mRNA levels of antioxidant enzymes were reduced (Gpx1, Cat, and Sod2) or were not altered (HO-1 and Sod1) as a function of PE treatment. In contrast, PE-treated mice with and without IR exposure displayed higher hepatic GSH concentrations than controls. Thus, ingestion of pomegranate polyphenols is associated with inhibition of x-ray-induced genomic instability and elevated GSH, which may reduce cancer risk. PMID- 27673357 TI - Sedation by Propofol for Painful Care Procedures at the End of Life: A Pilot Study. PROPOPAL 1. AB - BACKGROUND: At the end of life, patients may feel refractory pain during care procedures although they receive appropriate analgesia. They can benefit from a short-term sedation. Propofol is used for procedural sedation in emergency or reanimation departments. It may be adapted in a palliative care unit. OBJECTIVE: The main objective was to verify whether propofol could allow us to administer care without causing major pain to patients with refractory pain at the end of life. DESIGN: We conducted an open, prospective, and uncontrolled pilot study. SETTING/SUBJECTS: The study was conducted in one palliative care center in France. The subjects were patients with an estimated prognosis less than three months who experienced pain during care procedures, although they receive appropriate analgesia. RESULTS: Ten patients were included. Care was delivered with no major pain for 9 patients out of 10. The average duration of induction to reach deep sedation was 4 minutes (2-8) and of care procedures was 13 minutes (7 32). On average, the patient woke up 11.5 minutes after we stopped injecting propofol (7-18). Only one patient experienced a significant adverse effect caused by propofol, but it did not have any harmful consequence except the interruption of care procedures. CONCLUSION: Transitory sedation using propofol for terminally ill patients hospitalized in a palliative care unit can offer optimal comfort during painful care procedures without significant complications. Patients woke up quickly. Further studies will have to be conducted to verify these initial results and make sure there are no major drawbacks. PMID- 27673358 TI - Healing of the bone with anti-fracture drugs. AB - INTRODUCTION: Fracture healing is a complex physiological process. As impaired fracture healing is more frequent in osteoporotic subjects, anti-osteoporotic drugs could have some impact on this process. Areas covered: We reviewed the current literature to evaluate the effects of these drugs on fracture healing and their potential role in supporting this process, especially when impaired. A PubMed/Medline search was undertaken combining the terms 'fracture healing', 'anti-resorptive drugs', 'anabolic agents', 'anti-osteoporotic drugs'. Expert opinion: As clinical evidence on the role of anti-osteoporotic drugs in the process of fracture healing consists mainly of case reports or studies with a relatively small number of patients, large randomized clinical trials are needed in order to extend to the human setting the promising results on these agents as inductors or co-adjuvants of bone healing derived from animal studies. PMID- 27673360 TI - Association between Blood Glucose Levels the Day after Targeted Temperature Initiation and Outcome in Traumatic Brain Injury: A Post-Hoc Analysis of the B HYPO Study. AB - We investigated associations between blood glucose levels and clinical outcomes in participants of the multi-center randomized controlled Brain-Hypothermia (B HYPO) study. Patients with severe traumatic brain injury (TBI, Glasgow Coma Scale 4-8) were assigned to therapeutic hypothermia (TH, 32-34 degrees C, n = 98) or fever control (35.5-37.0 degrees C, n = 50) groups. TH patients were cooled as soon as possible for >=72 h and rewarmed at a rate of <1 degrees C/d. We recorded blood glucose (BG) levels on days 0, 1, and 3 after treatment initiation, and day 1 after rewarming. The Glasgow Outcome Scale was assessed at 6 months. Median BG levels decreased from day 0 to day 1 (163 vs. 132 mg/dL, p = 0.0062) in the fever control group. In contrast, a decrease was observed from day 1 to day 3 (157.5 vs. 126 mg/dL, p < 0.001) in the TH group. Day 1 BG was higher in the TH group compared with the fever control group (p = 0.0252). At day 0, BG levels were higher in non-survivors compared with survivors across all patients (p = 0.0035), the TH group (p = 0.0125), and the non-surgical group (p = 0.0236). Higher day 1 BG levels were observed in non-survivors compared with survivors across all patients (p = 0.0071), the fever control group (p = 0.0495), and the surgical group (p = 0.0364). In the TH group, the initial stress hyperglycemia was sustained the next day after TH induction. Day 1 BG predicted outcome in TBI patients with TH and fever control. Our findings indicate the significance of BG control particularly during TH treatment. PMID- 27673359 TI - The selective permeability barrier in the nuclear pore complex. AB - The nuclear pore complex (NPC) mediates the shuttle transport of macromolecules between the nucleus and cytoplasm in eukaryotic cells. The permeability barrier formed by intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG Nups) in the NPC functions as the critical selective control for nucleocytoplasmic transport. Signal-independent small molecules (< 40 kDa) passively diffuse through the pore, but passage of large cargo molecules is inhibited unless they are chaperoned by nuclear transport receptors (NTRs). NTRs are capable of interacting with FG-Nups and guide the cargos to cross the barrier by facilitated diffusion. The native conformation of the FG-Nups permeability barrier and the competition among multiple NTRs interacting with this barrier in the native NPCs are the 2 core questions still being highly debated in the field. Recently, we applied high-speed super-resolution fluorescence microscopy to map out the natural structure of the FG-Nups barrier and determined the competition among multiple NTRs as they interact with the barrier in the native NPCs. In this extra-view article, we will review the current understanding in the configuration and function of FG-Nups barrier and highlight the new evidence obtained recently to answer the core questions in nucleocytoplasmic transport. PMID- 27673361 TI - Medullary Thyroid Carcinoma Associated with Germline RETK666N Mutation. AB - BACKGROUND: Multiple endocrine neoplasia type 2 is an autosomal dominant inherited syndrome caused by activating mutations in the RET proto-oncogene. The RETK666N DNA variant was previously reported in two isolated medullary thyroid carcinoma (MTC) cases, but no family studies are available, and its oncogenic significance remains unknown. METHODS: The clinical features, genetic data, and family information of eight index MTC patients with a germline RETK666N variant were assessed. RESULTS: Four probands presented with MTC and extensive nodal metastasis, one with biopsy-confirmed distant metastasis. Two additional probands presented with localized disease. However, nodal status was not available. Of the final two probands, one had an incidental 1.5 mm MTC and C-cell hyperplasia uncovered after surgery for papillary thyroid carcinoma, and one had two foci of MTC (largest dimension 2.3 cm) detected after surgery for dysphagia. Genetic screening identified 16 additional family members carrying the K666N variant (aged 5-90 years), 11 of whom have documented evaluation for MTC. Of these, only two were found to have elevated basal serum calcitonin upon screening, and the remaining patients had calcitonin levels within the reference range. One patient who elected to have a thyroidectomy at 70 years of age was confirmed to have MTC. The other subject, 57 years old, elected surveillance. Four prophylactic thyroidectomies were performed, with one case of C-cell hyperplasia at 20 years and three cases that revealed normal pathology at ages 21, 30, and 30 years. None of the K666N DNA variant carriers had evidence of primary hyperparathyroidism or pheochromocytoma. CONCLUSIONS: From this case series, the largest such experience to date, it is concluded that the RETK666N variant is likely pathogenic and associated with low penetrance of MTC. However, the findings are insufficient to define its pathogenicity clearly and make firm recommendations for screening and treatment. Given the potential benefit associated with early detection of aberrant C-cell growth, and the noninvasive nature of genetic testing, "at risk" individuals should be screened, and if the K666N variant is identified, they should be managed using a personalized screening approach for detection of MTC. PMID- 27673362 TI - Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men. AB - PURPOSE: Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. METHODS: Results of anal cytology and HPV DNA were gathered for 83 individuals. RESULTS: Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. CONCLUSION: Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV. PMID- 27673363 TI - Serum metabolomic profiling of prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. AB - BACKGROUND: Two recent metabolomic analyses found serum lipid, energy, and other metabolites related to aggressive prostate cancer risk up to 20 years prior to diagnosis. METHODS: We conducted a serum metabolomic investigation of prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that included annual serum total prostate-specific antigen measurement and digital rectal examination. This nested study included 380 cases diagnosed post screening and 380 controls individually matched to cases on age, race, study centre, and blood-collection date (median time to diagnosis, 10 years (range 4.4 17 years)). Sera were analysed on a high-resolution accurate mass platform of ultrahigh-performance liquid and gas chromatography/mass spectroscopy that identified 695 known metabolites. Logistic regression conditioned on the matching factors estimated odds ratios (OR) and 95% confidence intervals of risk associated with an 80th percentile increase in the log-metabolite signal. RESULTS: Twenty-seven metabolites were associated with prostate cancer at P<0.05. Pyroglutamine, gamma-glutamylphenylalanine, phenylpyruvate, N-acetylcitrulline, and stearoylcarnitine showed the strongest metabolite-risk signals (ORs=0.53, 0.51, 0.46, 0.58, and 1.74, respectively; 0.001?P?0.006). Findings were similar for aggressive disease (peptide chemical class, P=0.03). None of the P-values were below the threshold of Bonferroni correction, however. CONCLUSIONS: A unique metabolomic profile associated with post-screening prostate cancer is identified that differs from that in a previously studied, unscreened population. PMID- 27673364 TI - Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder. AB - BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's alpha-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder. PMID- 27673366 TI - Novel Stannatrane N(CH2CMe2O)2(CMe2CH2O)SnO-t-Bu and Related Oligonuclear Tin(IV) Oxoclusters. Two Isomers in One Crystal. AB - The syntheses of the alkanolamine N(CH2CMe2OH)2(CMe2CH2OH) (1), of the stannatrane N(CH2CMe2O)2(CMe2CH2O)SnO-t-Bu (2), and of the trinuclear tin oxocluster 3 consisting of the two isomers [(MU3-O)(O-t Bu){Sn(OCH2CMe2)(OCMe2CH2)2N}3] (3a) and [(MU3-O)(MU3-O-t Bu){Sn(OCH2CMe2)(OCMe2CH2)2N}3] (3b) as well as the isolation of a few crystals of the hexanuclear tin oxocluster [LSnOSn(OH)3LSnOH]2 [L = N(CH2CMe2O)2(CMe2CH2O)] (4) are reported. The compounds were characterized by 1H, 13C, 15N, and 119Sn (1-3) nuclear magnetic resonance and infrared spectroscopy, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction analysis (1-4). A graph set analysis was performed for compound 1. The relative energies of 3a and 3b were estimated by density functional theory calculations that show that the energy differences are small. PMID- 27673365 TI - Emergence of resistance to tyrosine kinase inhibitors in non-small-cell lung cancer can be delayed by an upfront combination with the HSP90 inhibitor onalespib. AB - BACKGROUND: Tyrosine kinase inhibitors, such as crizotinib and erlotinib, are widely used to treat non-small-cell lung cancer, but after initial response, relapse is common because of the emergence of resistance through multiple mechanisms. Here, we investigated whether a frontline combination with an HSP90 inhibitor could delay the emergence of resistance to these inhibitors in preclinical lung cancer models. METHODS: The HSP90 inhibitor, onalespib, was combined with either crizotinib or erlotinib in ALK- or EGFR-activated xenograft models respectively (H2228, HCC827). RESULTS: In both models, after initial response to the monotherapy kinase inhibitors, tumour relapse was observed. In contrast, tumour growth remained inhibited when treated with an onalespib/kinase inhibitor combination. Analysis of H2228 tumours, which had relapsed on crizotinib monotherapy, identified a number of clinically relevant crizotinib resistance mechanisms, suggesting that HSP90 inhibitor treatment was capable of suppressing multiple mechanisms of resistance. Resistant cell lines, derived from these tumours, retained sensitivity to onalespib (proliferation and signalling pathways were inhibited), indicating that, despite their resistance to crizotinib, they were still sensitive to HSP90 inhibition. CONCLUSIONS: Together, these preclinical data suggest that frontline combination with an HSP90 inhibitor may be a method for delaying the emergence of resistance to targeted therapies. PMID- 27673367 TI - alpha-Glucosidase Inhibitors from Preussia minimoides ?. AB - Extensive fractionation of an extract from the grain-based culture of the endophytic fungus Preussia minimoides led to the isolation of two new polyketides with novel skeletons, minimoidiones A (1) and B (2), along with the known compounds preussochromone C (3), corymbiferone (4), and 5-hydroxy-2,7-dimethoxy-8 methylnaphthoquinone (5). The structures of 1 and 2 were elucidated using 1D and 2D NMR data analysis, along with DFT calculations of 1H NMR chemical shifts. The absolute configuration of 1 was established by a single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Compounds 1-4 significantly inhibited yeast alpha-glucosidase. PMID- 27673368 TI - Thermally-Induced Triple-Shape Hydrogels: Soft Materials Enabling Complex Movements. AB - Shape-memory hydrogels enable directed movements of a specimen in response to temperature, whereby crystallizable switching segments incorporated as side chains resulted in constant degrees of swelling during the shape-memory cycle. Here we report about hydrogels exhibiting a thermally induced triple-shape effect that allows complex movements of soft materials with two almost independent shape changes. Potential applications for those soft triple-shape materials are two step self-unfolding devices or temperature-sensitive hydrogel actuators, for example, smart valves for flow rate control in aqueous media. Series of hydrogels with two different hydrophobic crystallizable switching segments were prepared. The degrees of swelling of the triple-shape hydrogels were not affected for different shapes or temperatures, which avoided in this way interferences on the shape shifts. During the two-step programming procedure, two distinct shapes can be implemented as reflected by shape fixity ratios of generally >50%. Structural analysis of the switching domains during the triple-shape cycle by means of X-ray scattering indicates that longer side chains gain lower orientation after deformation and that shorter side chains orient perpendicular to the hydrophilic main chain. Furthermore, it is observed that increased orientation of the switching domains is not a key requirement for adequate shape fixity and recovery ratios of the triple-shape effect in hydrogels, thus longer side chains can be utilized as switching segments in other shape-memory hydrogels. PMID- 27673369 TI - Web Server for Peak Detection, Baseline Correction, and Alignment in Two Dimensional Gas Chromatography Mass Spectrometry-Based Metabolomics Data. AB - Two-dimensional gas chromatography time-of-flight mass spectrometry (GC*GC/TOF MS) is superior for chromatographic separation and provides great sensitivity for complex biological fluid analysis in metabolomics. However, GC*GC/TOF-MS data processing is currently limited to vendor software and typically requires several preprocessing steps. In this work, we implement a web-based platform, which we call GC2MS, to facilitate the application of recent advances in GC*GC/TOF-MS, especially for metabolomics studies. The core processing workflow of GC2MS consists of blob/peak detection, baseline correction, and blob alignment. GC2MS treats GC*GC/TOF-MS data as pictures and clusters the pixels as blobs according to the brightness of each pixel to generate a blob table. GC2MS then aligns the blobs of two GC*GC/TOF-MS data sets according to their distance and similarity. The blob distance and similarity are the Euclidean distance of the first and second retention times of two blobs and the Pearson's correlation coefficient of the two mass spectra, respectively. GC2MS also directly corrects the raw data baseline. The analytical performance of GC2MS was evaluated using GC*GC/TOF-MS data sets of Angelica sinensis compounds acquired under different experimental conditions and of human plasma samples. The results show that GC2MS is an easy-to use tool for detecting peaks and correcting baselines, and GC2MS is able to align GC*GC/TOF-MS data sets acquired under different experimental conditions. GC2MS is freely accessible at http://gc2ms.web.cmdm.tw . PMID- 27673370 TI - Kinetics Aspects of the Reversible Assembly of Copper in Heterometallic Mo3CuS4 Clusters with 4,4'-Di-tert-butyl-2,2'-bipyridine. AB - Treatment of the triangular [Mo3S4Cl3(dbbpy)3]Cl cluster ([1]Cl) with CuCl produces a novel tetrametallic cuboidal cluster [Mo3(CuCl)S4Cl3(dbbpy)3][CuCl2] ([2][CuCl2]), whose crystal structure was determined by X-ray diffraction (dbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine). This species, which contains two distinct types of Cu(I), is the first example of a diimine-functionalized heterometallic M3M'S4 cluster. Kinetics studies on both the formation of the cubane from the parent trinuclear cluster and its dissociation after treatment with halides, supported by NMR, electrospray ionization mass spectrometry, cyclic voltammetry, and density functional theory calculations, are provided. On the one hand, the results indicate that addition of Cu(I) to [1]+ is so fast that its kinetics can be monitored only by cryo-stopped flow at -85 degrees C. On the other hand, the release of the CuCl unit in [2]+ is also a fast process, which is unexpectedly assisted by the CuCl2- counteranion in a process triggered by halide (X-) anions. The whole set of results provide a detailed picture of the assembly-disassembly processes in this kind of cluster. Interconversion between trinuclear M3S4 clusters and their heterometallic M3M'S4 derivatives can be a fast process occurring readily under the conditions employed during reactivity and catalytic studies, so their occurrence is a possibility that must be taken into account in future studies. PMID- 27673371 TI - Reversible Covalent Binding to Cardiac Troponin C by the Ca2+-Sensitizer Levosimendan. AB - The binding of Ca2+ to cardiac troponin C (cTnC) triggers contraction in heart muscle. In the diseased heart, the myocardium is often desensitized to Ca2+, which leads to impaired contractility. Therefore, compounds that sensitize cardiac muscle to Ca2+ (Ca2+-sensitizers) have therapeutic promise. The only Ca2+ sensitizer used regularly in clinical settings is levosimendan. While the primary target of levosimendan is thought to be cTnC, the molecular details of this interaction are not well understood. In this study, we used mass spectrometry, computational chemistry, and nuclear magnetic resonance spectroscopy to demonstrate that levosimendan reacts specifically with cysteine 84 of cTnC to form a reversible thioimidate bond. We also showed that levosimendan only reacts with the active, Ca2+-bound conformation of cTnC. Finally, we propose a structural model of levosimendan bound to cTnC, which suggests that the Ca2+ sensitizing function of levosimendan is due to stabilization of the Ca2+-bound conformation of cTnC. PMID- 27673372 TI - Diffusion in Homogeneous and in Inhomogeneous Media: A New Unified Approach. AB - We propose a new method to calculate the diffusion coefficient within molecular dynamics simulations for either homogeneous or inhomogeneous fluids. We formulate such method by solving analytically the Smoluchowski equation for a linear potential of mean force within a thin layer with absorbing boundary conditions. The bulk, or homogeneous, fluid diffusion emerges as a particular case in this approach. We apply this method to bulk liquid water at atmospheric pressure and different temperatures using the SPC/E water force field. We show that our method gives results as accurate as the traditional Einstein-Smoluchowski method, avoiding the fitting procedure required in the traditional method. We also apply this method for molten sodium chloride showing its applicability for multicomponent systems. The water vapor-liquid interface is studied as an example of an inhomogeneous system. We calculate all the components of the diffusion tensor at the interface. We observe the same anisotropy between the perpendicular and the parallel components at the interface as it has been noted in the literature. We also calculate the perpendicular self-diffusion coefficient of methane near the calcite surface showing that this coefficient is much lower than the parallel diffusion coefficients. We believe that this new unified approach is a very promising technique for both bulk and confined media. PMID- 27673373 TI - Vulvodynia: When a Paradigm Challenges the Management. PMID- 27673374 TI - Gynecologists' Knowledge, Attitudes, and Intentions Toward Human Papillomavirus Vaccination in Serbia. AB - OBJECTIVES: The aims of this study were to estimate the level of knowledge, attitudes, and intentions about human papillomavirus (HPV) infection and HPV vaccine among gynecologists and to explore predictors of gynecologists' intention to recommend the HPV vaccine. METHOD: This research was conducted between April and June 2014 among all gynecologists working at women's health departments in all primary health centers in Belgrade, the capital of Serbia, using a specially designed questionnaire. RESULTS: The response rate was 88.2%. The knowledge of gynecologists was estimated as average. The most frequently reported obstacles to HPV vaccination was the financial concern (59.8%). More than two thirds of the gynecologists were willing to recommend the vaccine (68.4%). The factors associated with the gynecologists' intention to recommend the vaccine included their positive attitudes toward boys' vaccination (odds ratio [OR], 8.96; 95% confidence interval [CI], 2.85-28.16), negative attitudes toward frequent changes the recommendations (OR, 0.31; 95% CI, 0.10-0.93), and beliefs that the vaccine application would decrease condom usage (OR, 0.31; 95% CI, 0.06-0.68). CONCLUSIONS: The findings provide an important insight into the current point of view of the gynecologists, which confirms that the better the knowledge of HPV and vaccine, the higher the likelihood of recommending it. PMID- 27673375 TI - Efficient Photochemical Dihydrogen Generation Initiated by a Bimetallic Self Quenching Mechanism. AB - Artificial photosynthesis relies on coupling light absorption with chemical fuel generation. A mechanistic study of visible light-driven H2 production from [Cp*Ir(bpy)H]+ (1) has revealed a new, highly efficient pathway for integrating light absorption with bond formation. The net reaction of 1 with a proton source produces H2, but the rate of excited state quenching is surprisingly acid independent and displays no observable deuterium kinetic isotopic effect. Time resolved photoluminescence and labeling studies are consistent with diffusion limited bimetallic self-quenching by electron transfer. Accordingly, the quantum yield of H2 release nearly reaches unity as the concentration of 1 increases. This unique pathway for photochemical H2 generation provides insight into transformations catalyzed by 1. PMID- 27673376 TI - Model Simulations of the Thermal Dissociation of the TIK(H+)2 Tripeptide: Mechanisms and Kinetic Parameters. AB - Direct dynamics simulations, utilizing the RM1 semiempirical electronic structure theory, were performed to study the thermal dissociation of the doubly protonated tripeptide threonine-isoleucine-lysine ion, TIK(H+)2, for temperatures of 1250 2500 K, corresponding to classical energies of 1778-3556 kJ/mol. The number of different fragmentation pathways increases with increase in temperature. At 1250 K there are only three fragmentation pathways, with one contributing 85% of the fragmentation. In contrast, at 2500 K, there are 61 pathways, and not one dominates. The same ion is often formed via different pathways, and at 2500 K there are only 14 m/z values for the product ions. The backbone and side-chain fragmentations occur by concerted reactions, with simultaneous proton transfer and bond rupture, and also by homolytic bond ruptures without proton transfer. For each temperature the TIK(H+)2 fragmentation probability versus time is exponential, in accord with the Rice-Ramsperger-Kassel-Marcus and transition state theories. Rate constants versus temperature were determined for two proton transfer and two bond rupture pathways. From Arrhenius plots activation energies Ea and A-factors were determined for these pathways. They are 62-78 kJ/mol and (2 3) * 1012 s-1 for the proton transfer pathways and 153-168 kJ/mol and (2-4) * 1014 s-1 for the bond rupture pathways. For the bond rupture pathways, the product cation radicals undergo significant structural changes during the bond rupture as a result of hydrogen bonding, which lowers their entropies and also their Ea and A parameters relative to those for C-C bond rupture pathways in hydrocarbon molecules. The Ea values determined from the simulation Arrhenius plots are in very good agreement with the reaction barriers for the RM1 method used in the simulations. A preliminary simulation of TIK(H+)2 collision-induced dissociation (CID), at a collision energy of 13 eV (1255 kJ/mol), was also performed to compare with the thermal dissociation simulations. Though the energy transferred to TIK(H+)2 in the collisions is substantially less than the energy for the thermal excitations, there is substantial fragmentation as a result of the localized, nonrandom excitation by the collisions. CID results in different fragmentation pathways with a significant amount of short time nonstatistical fragmentation. Backbone fragmentation is less important, and side-chain fragmentation is more important for the CID simulations as compared to the thermal simulations. The thermal simulations provide information regarding the long-time statistical fragmentation. PMID- 27673379 TI - Nanostructured Stealth Surfaces for Visible and Near-Infrared Light. AB - So far, all previous attempts to apply nanostructures for perfect transmission have not achieved maximum transmittance beyond 99.5% due to the limited regularity of the nanoscale surface geometry: too low for many high-end applications. Here we demonstrate a nanostructured stealth surface, with minimal reflectance (<0.02%) and maximal transmittance (>99.8%) for a wavelength range, covering visible and near-infrared. Compared to multilayer thin film coatings for near-infrared applications our antireflective surfaces operate within a much broader wavelength range, are mechanical stable to resist human touch or contamination, show a 44% higher laser-induced damage threshold, and are suitable for bended interfaces such as microlenses as well. PMID- 27673378 TI - Minimal Incision, Multifidus-sparing Microendoscopic Diskectomy Versus Conventional Microdiskectomy for Highly Migrated Intracanal Lumbar Disk Herniations. AB - BACKGROUND: Highly migrated intracanal disk herniation is not among the exclusion criteria of the interlaminar microendoscopic diskectomy (MED) procedure. The goal of this prospective, randomized, controlled study was to compare the effect of the size of the skin incision and the method of handling the multifidus muscle on the results of the interlaminar MED procedure versus conventional microdiskectomy in retrieving highly migrated intracanal disk herniations. METHODS: Seventy-three patients with highly migrated intracanal lumbar disk herniations treated with either minimal incision, multifidus-sparing MED or conventional microdiskectomy were observed for 2 years. Primary (clinical) outcomes data included the results of the Numerical Rating Scale (NRS) for back and leg pain and the Oswestry Disability Index (ODI) to quantify pain and disability, respectively. Secondary objective outcomes data included surgical time, blood loss, postoperative analgesics, length of hospital stay, time to return to work, the rates of revision surgery complications, and the results of the patient satisfaction index (PSI) and the modified MacNab criteria. RESULTS: At final follow-up, relief of leg pain was statistically significant for both groups. NRS back pain, ODI, PSI, and the modified MacNab criteria showed no improvement in the conventional microdiskectomy group. Secondary outcomes data in the MED group were significantly better than those for the control group. CONCLUSIONS: Highly migrated intracanal lumbar disk herniations can be sufficiently retrieved using minimal incision, multifidus-sparing MED, which is an effective alternative to conventional microdiskectomy. The minimal skin incision and multifidus-sparing approach of the MED had a positive effect on clinical outcomes, which were stable throughout the 2-year follow-up period. LEVEL OF EVIDENCE: Therapeutic level II. PMID- 27673377 TI - Soft-tissue Defects After Total Knee Arthroplasty: Management and Reconstruction. AB - Wound healing complications associated with total knee arthroplasty present a considerable challenge to the orthopaedic surgeon. To ensure preservation of a functional joint, the management of periprosthetic soft-tissue defects around the knee requires rapid assessment, early and aggressive debridement, and durable, contoured coverage. Several reconstructive options are available to tailor soft tissue coverage to the location, size, and depth of the wound. Special consideration should be given to the timing of the intervention, management of infection, and prosthesis salvage. The merits of each reconstructive option, including perforator, fasciocutaneous, muscular, and free microvascular flaps, should be weighed to select the most appropriate option. The proposed approach can guide surgeons in treating patients with these complex soft-tissue defects. PMID- 27673380 TI - Cytokines and intestinal inflammation. AB - PURPOSE OF REVIEW: Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. RECENT FINDINGS: The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-alpha, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa protective function in acute injury but proinflammatory effects during chronic inflammation. SUMMARY: The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine specific therapies. PMID- 27673381 TI - Translating nutritional immunology into drug development for inflammatory bowel disease. AB - PURPOSE OF REVIEW: To highlight recent advances in the understanding of nutritional immunology and in the development of novel therapeutics for inflammatory bowel disease (IBD). RECENT FINDINGS: We highlight the variety of factors that contribute to the interaction of the immune system and nutrition including the microbiome and the nervous system stimulation of the gut. We describe the potential for therapeutic development in IBD. Further, we review the cellular metabolic effects on immune activation and promising therapeutic targets. Finally, we show how the progression of understanding the role of lanthionine synthetase C-like 2 has encompassed both nutritional and therapeutic advances and led to the development of novel oral small molecule therapeutics for IBD. SUMMARY: Nutritional immunology and drug development research centered around immunoregulatory pathways can provide safer and more effective drugs while accelerating the path to cures. PMID- 27673382 TI - Palladium-Catalyzed Decarbonylative Cross-Coupling of Azinecarboxylates with Arylboronic Acids. AB - The first palladium-catalyzed decarbonylative coupling of phenyl 2 azinecarboxylates and arylboronic acids is presented. The key for the development of this decarbonylative coupling is the use of Pd/dcype as a catalyst. A wide range of 2-azinecarboxylates can undergo the present coupling reaction to afford 2-arylazines. By combination with previously reported nickel-catalyzed decarbonylative coupling, we achieved a chemoselective sequential decarbonylative coupling of pyridine dicarboxylate to synthesize 2,4-diarylpyridine. PMID- 27673384 TI - Evaluating the Performance of the Pediatric Acute Lung Injury Consensus Conference Definition of Acute Respiratory Distress Syndrome. AB - OBJECTIVE: The Pediatric Acute Lung Injury Consensus Conference has developed a pediatric-specific definition of acute respiratory distress syndrome, which is a significant departure from both the Berlin and American European Consensus Conference definitions. We sought to test the external validity and potential impact of the Pediatric Acute Lung Injury Consensus Conference definition by comparing the number of cases of acute respiratory distress syndrome and mortality rates among children admitted to a multidisciplinary PICU when classified by Pediatric Acute Lung Injury Consensus Conference, Berlin, and American European Consensus Conference criteria. DESIGN: Retrospective cohort study. SETTING: Tertiary care, university-affiliated PICU. PATIENTS: All patients admitted between March 2009 and April 2013 who met inclusion criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 4,764 patients admitted to the ICU, 278 (5.8%) met Pediatric Acute Lung Injury Consensus Conference pediatric acute respiratory distress syndrome criteria with a mortality rate of 22.7%. One hundred forty-three (32.2% mortality) met Berlin criteria, and 134 (30.6% mortality) met American European Consensus Conference criteria. All patients who met American European Consensus Conference criteria and 141 (98.6%) patients who met Berlin criteria also met Pediatric Acute Lung Injury Consensus Conference criteria. The 137 patients who met Pediatric Acute Lung Injury Consensus Conference but not Berlin criteria had an overall mortality rate of 13.1%, but 29 had severe acute respiratory distress syndrome with 31.0% mortality. At acute respiratory distress syndrome onset, there was minimal difference in mortality between mild or moderate acute respiratory distress syndrome by both Berlin (32.4% vs 25.0%, respectively) and Pediatric Acute Lung Injury Consensus Conference (16.7% vs 18.6%, respectively) criteria, but higher mortality for severe acute respiratory distress syndrome (Berlin, 43.6%; Pediatric Acute Lung Injury Consensus Conference, 37.0%). Twenty four hours after acute respiratory distress syndrome onset, the presence of severe acute respiratory distress syndrome (using either Berlin or Pediatric Acute Lung Injury Consensus Conference) was associated with nearly 50% mortality. CONCLUSIONS: Applying the Pediatric Acute Lung Injury Consensus Conference definition of acute respiratory distress syndrome has the potential to significantly increase the number of acute respiratory distress syndrome patients identified, with a lower overall mortality rate. However, severe acute respiratory distress syndrome is associated with extremely high mortality, particularly if present at 24 hours after initial diagnosis. PMID- 27673385 TI - Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. AB - OBJECTIVE: We compared efficacy of dopamine and epinephrine as first-line vasoactive therapy in achieving resolution of shock in fluid-refractory hypotensive cold septic shock. DESIGN: Double-blind, pilot, randomized controlled study. SETTING: Pediatric emergency and ICU of a tertiary care teaching hospital. PATIENTS: Consecutive children 3 months to 12 years old, with fluid-refractory hypotensive septic shock, were enrolled between July 2013 and December 2014. INTERVENTION: Enrolled children were randomized to receive either dopamine (in incremental doses, 10 to 15 to 20 MUg/kg/min) or epinephrine (0.1 to 0.2 to 0.3 MUg/kg/min) till end points of resolution of shock were achieved. After reaching maximum doses of test drugs, open-label vasoactive was started as per discretion of treating team. Primary outcome was resolution of shock within first hour of resuscitation. The study was registered (CTRI/2014/02/004393) and was approved by institute ethics committee. MEASUREMENTS AND MAIN RESULTS: We enrolled 29 children in epinephrine group and 31 in dopamine group. Resolution of shock within first hour was achieved in greater proportion of children receiving epinephrine (n = 12; 41%) than dopamine (n = 4; 13%) (odds ratio, 4.8; 95% CI, 1.3-17.2; p = 0.019); the trend persisted even at 6 hours (48.3% vs 29%; p = 0.184). Children in epinephrine group had lower Sequential Organ Function Assessment score on day 3 (8 vs 12; p = 0.05) and more organ failure-free days (24 vs 20 d; p = 0.022). No significant difference in adverse events (16.1% vs 13.8%; p = 0.80) and mortality (58.1% vs 48.3%; p = 0.605) was observed between the two groups. CONCLUSION: Epinephrine is more effective than dopamine in achieving resolution of fluid-refractory hypotensive cold shock within the first hour of resuscitation and improving organ functions. PMID- 27673386 TI - Metastatic Malignant Pilomatrixoma in an 8-Year-Old Girl Misdiagnosed as a Recurrent Pilomatrixoma. AB - Malignant pilomatrixoma or pilomatrix carcinoma is a rare, locally aggressive malignant neoplasm, derived from the hair follicle with a high propensity for local recurrence. Only a few cases of metastatic pilomatrixoma have been described in the literature. Till date, only 17 cases have been reported in the English-language medical literature, most commonly occurring associated with local recurrence in adults. We report the first case in children of a metastatic malignant pilomatrixoma in an 8-year-old girl presenting with a recurrent pilomatrix carcinoma of the forehead with metastases in cervical and parotid lymph nodes. PMID- 27673387 TI - Eccrine Duct Dilation as a Marker of Cicatricial Alopecia. AB - BACKGROUND: Eccrine duct dilation (EDD) and syringoma-like sweat duct proliferation have been described as reactive changes occurring in a variety of skin conditions. However, extensive evaluation of EDD in scalp biopsies performed for alopecia has not been performed. METHODS: We retrospectively examined 129 cases of cicatricial alopecia (lichen planopilaris, central centrifugal cicatricial alopecia, and discoid lupus erythematosus) and 130 cases of noncicatricial alopecias (androgenetic alopecia, telogen effluvium, and alopecia areata) for the presence of EDD. RESULTS: Overall, EDD occurred in 4% (5/130) of noncicatricial alopecia (2/43 of androgenetic alopecia, 0/15 of telogen effluvium, 3/72 of alopecia areata) and 35% (45/129) of cicatricial alopecia (10/31 of lichen planopilaris, 17/36 central centrifugal cicatricial alopecia, and 18/62 of discoid lupus erythematosus; P < 0.0001) cases. CONCLUSIONS: EDD can infrequently occur in noncicatricial alopecias; however, the frequency of dilation is significantly increased in cicatricial alopecias. This alteration may be due to compressive or inflammatory effects inherent to the scarring process. The presence of EDD may be a useful adjunctive histopathologic feature in the diagnosis of cicatricial alopecias. PMID- 27673388 TI - Merkel Cell Carcinoma Arising in an Epidermal Cyst. AB - Merkel cell carcinoma is a rare aggressive primary cutaneous neuroendocrine tumor. It is associated mostly with malignant skin lesions. Rare cases in the literature described its association with benign skin adnexal lesions. We present here an additional case of Merkel cell carcinoma arising from an epidermal cyst located in the left arm of a 57-year-old male. The tumor was composed of lobules of monotonous round cells with dusty chromatin. It was positive for cytokeratin 20 and neuroendocrine markers. Patient was treated with surgical resection and radiation to the axilla. He is well and free of disease after 5 years of follow up. PMID- 27673389 TI - Periodic Acid-Schiff Stain in Circumscribed Hypokeratosis. PMID- 27673390 TI - Structural Changes in 2D BiSe Bilayers as n Increases in (BiSe)1+delta(NbSe2)n (n = 1-4) Heterostructures. AB - (BiSe)1+delta(NbSe2)n heterostructures with n = 1-4 were synthesized using modulated elemental reactants. The BiSe bilayer structure changed from a rectangular basal plane with n = 1 to a square basal plane for n = 2-4. The BiSe in-plane structure was also influenced by small changes in the structure of the precursor, without significantly changing the out-of-plane diffraction pattern or value of the misfit parameter, delta. Density functional theory calculations on isolated BiSe bilayers showed that its lattice is very flexible, which may explain its readiness to adjust shape and size depending on the environment. Correlated with the changes in the BiSe basal plane structure, analysis of scanning transmission electron microscope images revealed that the occurrence of antiphase boundaries, found throughout the n = 1 compound, is dramatically reduced for the n = 2-4 compounds. X-ray photoelectron spectroscopy measurements showed that the Bi 5d3/2, 5d5/2 doublet peaks narrowed toward higher binding energies as n increased from 1 to 2, also consistent with a reduction in the number of antiphase boundaries. Temperature-dependent electrical resistivity and Hall coefficient measurements of nominally stoichiometric samples in conjunction with structural refinements and XPS data suggest a constant amount of interlayer charge transfer independent of n. Constant interlayer charge transfer is surprising given the changes in the BiSe in-plane structure. The structural flexibility of the BiSe layer may be useful in designing multiple constituent heterostructures as an interlayer between structurally dissimilar constituents. PMID- 27673391 TI - Controlling the Formation and Structure of Nanoparticle Superlattices through Surface Ligand Behavior. AB - The tailoring of nanoparticle superlattices is fundamental to the design of novel nanostructured materials and devices. To obtain specific collective properties of these nanoparticle superlattices, reliable protocols for their self-assembly are required. This study provides insight into the self-assembly process by using oleate-covered CeO2 nanoparticles (cubic and polyhedral shapes) through the correlation of experimental and theoretical investigations. The self-assembly of CeO2 nanoparticles is controlled by tuning the colloid deposition parameters (temperature and evaporation rate), and the ordered structures so obtained were correlated to the Gibbs free energy variation of the system. The analysis of the interparticle force contributions for each structure showed the importance of both the effective ligand mean size and its Flory-Huggins parameter in determining the total potential energies. Additionally, the roles of ligand solubility and effective mean size were used to understand the formation of specific superlattice phases as a function of temperature and ligand accommodation in the arrangement. Furthermore, the face-to-face interactions between nanoparticles were correlated to the type of exposed crystallographic facet in each particle. PMID- 27673392 TI - Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease. AB - BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the benefits and risks associated with the use of bronchodilators in people with acute chest syndrome. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2002) and Embase (1981 to 2002).Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 11 July 2016. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease. PMID- 27673393 TI - Leadership, Loss and What We Wore. PMID- 27673394 TI - Remembering Dorothy Wylie, 1929-2016. PMID- 27673396 TI - Impact of a Leadership Development Institute on Professional Lives and Careers. AB - An evaluation study was conducted to determine the impact of a leadership institute, The Dorothy Wylie Health Leaders Institute (DWHLI), over the decade since its inception. The aim was to better understand the perceived influence of the Institute over time on professional lives and careers of alumni and identify the critical design features that supported leadership development. Nurses and other health disciplines from all levels of leadership and from most provinces completed an online survey (n = 165) and a subset was interviewed (n = 33). The majority of alumni (50-68%) rated the impact of the Institute as significant or very significant on seven of the eight selected intended leadership outcomes. For 73-78% of the alumni, the Institute had a recurring or profound positive impact on their professional lives as leaders and personal careers. Alumni who reported the greatest impact of the program on their knowledge, skills and confidence as leaders also had higher levels of career satisfaction and work engagement. Design elements that impacted their development included the theoretical and conceptual content, interactive and experiential structure and mentoring. Recommendations for organizational sponsors included the need for opportunities to apply learning, ongoing coaching, mentoring and career counseling specific to their leadership career path. PMID- 27673395 TI - Letter to the Editor. PMID- 27673397 TI - A Powerful New Partnership to Build Leadership Capacity in Healthcare in Canada. PMID- 27673398 TI - Dorothy Wylie Health Leaders Institute: "If You Build It, They Will Come". PMID- 27673399 TI - Sustaining a Focus on Transformative Change. PMID- 27673400 TI - My Leadership Story: Reflections of a Health Leaders Institute Alumnus. PMID- 27673401 TI - An Assessment of How Nurse Practitioners Create Access to Primary Care in Canadian Residential Long-Term Care Settings. AB - The aim of this paper is to explore the role and activities of nurse practitioners (NPs) working in long-term care (LTC) to understand concepts of access to primary care for residents. Utilizing the "FIT" framework developed by Penchanksy and Thomas, we used a directed content analysis method to analyze data from a pan-Canadian study of NPs in LTC. Individual and focus group interviews were conducted at four sites in western, central and eastern regions of Canada with 143 participants, including NPs, RNs, regulated and unregulated nursing staff, allied health professionals, physicians, administrators and directors and residents and family members. Participants emphasized how the availability and accessibility of the NP had an impact on access to primary and urgent care for residents. Understanding more about how NPs affect access in Canadian LTC will be valuable for nursing practice and healthcare planning and policy and may assist other countries in planning for the introduction of NPs in LTC settings to increase access to primary care. PMID- 27673402 TI - Nurse Leaders' Perceptions of Influence of Organizational Restructuring on Evidence-Informed Decision-Making. AB - AIM: To describe how organizational context and restructuring influenced nurse leaders' use of evidence in decision-making in their management practice. METHOD: Qualitative descriptive study. Fifteen leaders at executive and front-line manager levels in one organization were interviewed using a semi-structured format. FINDINGS: Inductive content analysis generated five main themes: leaders strove to keep relationships that preserve best decision-making ability; and sought the best knowledge to inform their decisions. However, a context of constant change; more scope; less autonomy; and decisional inertia in a sea of change had profound effects on their ability to employ evidence in decision making. IMPLICATIONS: Evidence-informed decision-making is a dynamic social process highly influenced by political instability in work environments. Organizational restructuring creates threats to common decision-making strategies, including information flow, relationships and priority setting. Healthcare restructuring is now a global constant, and there is a need for hospital leaders to understand and mitigate the effect restructuring has on the ability of leaders to engage in evidence-informed decision-making. Strategies are proposed to manage uncertainty and support nurse leaders in their evidence informed decision-making to deliver quality health services. This research provides an in-depth examination of how evidence-informed decision-making is influenced in the context of instability and uncertainty due to ever-present organizational restructuring. PMID- 27673403 TI - Partnership, Trust and Leadership among Nursing Researchers. AB - Members of a nursing research cluster realized that they needed to determine whether, given their diverse philosophies, they could formulate a collective research agenda responding to an administrative recommendation. The cluster's leaders conducted an appraisal of the role and importance of trust as an element for promoting collaboration in a nursing research cluster and for building a collective social identity. The Social Exchange Theory framed the appraisal. A survey and a facilitation session about trust in research partnerships were conducted with eight female nursing researchers/faculty. Facilitation day's discussion was fully audio recorded, transcribed verbatim and the content coded using ATLAS.ti 6. Thematic analysis was employed to analyze the qualitative aspects of the recorded discussion and the survey questionnaire explanatory responses. Responses to survey closed-questions were compiled as descriptive statistics. Participants revealed that mutual support, valuing each other and working collaboratively facilitated trust in intellectual partnership. Hindering factors were an environment suppressing expression of ideas and views, lack of open dialogue and decision-making among team members and lack of a sense of belonging. This paper has the potential to contribute to the knowledge of nursing leaders who are intending to develop and sustain nursing research teams in both academic and non-academic organizations. The paper will be especially useful as they deal with issues of trust in intellectual partnership in diverse settings. PMID- 27673405 TI - DNA barcode variability and host plant usage of fruit flies (Diptera: Tephritidae) in Thailand. AB - The objectives of this study were to examine the genetic variation in fruit flies (Diptera: Tephritidae) in Thailand and to test the efficiency of the mitochondrial cytochrome c oxidase subunit I (COI) barcoding region for species level identification. Twelve fruit fly species were collected from 24 host plant species of 13 families. The number of host plant species for each fruit fly species ranged between 1 and 11, with Bactrocera correcta found in the most diverse host plants. A total of 123 COI sequences were obtained from these fruit fly species. Sequences from the NCBI database were also included, for a total of 17 species analyzed. DNA barcoding identification analysis based on the best close match method revealed a good performance, with 94.4% of specimens correctly identified. However, many specimens (3.6%) had ambiguous identification, mostly due to intra- and interspecific overlap between members of the B. dorsalis complex. A phylogenetic tree based on the mitochondrial barcode sequences indicated that all species, except for the members of the B. dorsalis complex, were monophyletic with strong support. Our work supports recent calls for synonymization of these species. Divergent lineages were observed within B. correcta and B. tuberculata, and this suggested that these species need further taxonomic reexamination. PMID- 27673404 TI - Executive functions, parental punishment, and aggression: Direct and moderated relations. AB - The main focus of the current study was to assess whether executive functions (EFs) moderate the effect of parental punishment on adolescent aggression. The sample were 370 participants (53% girls, 47% boys) enrolled at secondary and higher secondary levels and ranged in age between 13-19 years (M = 15.5, SD = 1.3). Participants were assessed on a self-report measure of aggression and two punishment measures, in addition to a demographic sheet. Then, they were individually assessed on four tests taken from the Delis-Kaplan Executive Functions System (D-KEFS) namely Trial Making Test (TMT), Design Fluency Test (DFT), Color Word Interference Test (CWIT), and Card Sorting Test (CST) to assess cognitive flexibility, nonverbal fluency, inhibition, and problem-solving ability, respectively. Correlation coefficients indicated that all four executive functioning measures and the two punishment measures were significantly correlated with aggression. Moderation analysis indicated that all EFs moderated the relationship between physical punishment and aggression, and only inhibition and problem-solving ability, but not cognitive flexibility and nonverbal fluency, moderated the relations between symbolic punishment and aggression. The findings support the hypothesis that EFs are protective personal factors that promote healthy adolescent adjustment in the presence of challenging environmental factors. PMID- 27673406 TI - Caregiver stressors and depressive symptoms among older husbands and wives in the United States. AB - Framed by Pearlin's Stress Process Model, this study prospectively examines the effects of primary stress factors reflecting the duration, amount, and type of care on the depressive symptoms of spousal caregivers over a2-year period, and whether the effects of stressors differ between husbands and wives. Data are from the 2004 and 2006 waves of the Health and Retirement Study and we included community-dwelling respondents providing activities of daily life (ADL) and/or instrumental activities of daily life (IADL) help to their spouses/partners (N = 774). Results from multivariate regression models indicate that none of the primary stressors were associated with depressive symptoms. However, wives providing only personal care had significantly more depressive symptoms than wives providing only instrumental care, while husbands providing different types of care showed no such differences. To illuminate strategies for reducing the higher distress experienced by wife caregivers engaged in personal care assistance, further studies are needed incorporating couples' relational dynamics and gendered experiences in personal care. PMID- 27673407 TI - Cytomorphology and Histology Correlation of Rosai-Dorfman Disease: A 15-Year Study from a Tertiary Referral Centre in South India. AB - OBJECTIVES: Rosai-Dorfman disease (RDD) is an uncommon, benign histiocytic disorder of unknown etiology, typically presenting in young adulthood. We highlight the cytomorphology of RDD and correlate it with the histopathology. STUDY DESIGN: All cases diagnosed as RDD on fine-needle aspiration cytology between January 2001 and June 2015 were included. Clinical details were obtained from medical records. The cytology smears were reviewed along with the histopathology and immunohistochemistry, wherever available. RESULTS: The study included 10 cases ranging in age from 11 to 68 years (median 29). There was a male predominance with a male:female ratio of 1.5:1. The patients commonly presented with bilateral cervical lymphadenopathy. Extranodal involvement was seen in 2 cases in the nose and mandible, respectively. Of these 10 cases, 8 were later biopsied. The cytological features included numerous crescentic histiocytes, emperipolesis, reactive lymphocytes and plasma cells. A histological diagnosis of RDD was made in 7 out of 8 cases, and 1 was diagnosed as Hodgkin lymphoma. CONCLUSION: FNA represents an efficient, minimally invasive, cost effective and reliable technique for the diagnosis of RDD and may obviate the need for further biopsy. However, the disease has close differential diagnoses, including Langerhans cell histiocytosis, granulomatous lesions, and Hodgkin lymphoma. Hence, it must be remembered that there can be pitfalls when the diagnosis is made by cytology alone. PMID- 27673409 TI - MicroRNA and Long Non-Coding RNA in Ovarian Carcinoma: Translational Insights and Potential Clinical Applications. AB - Reliable biomarkers for the detection of early ovarian carcinoma are currently unavailable. MicroRNA and long non-coding RNA may be important in cancer initiation and progression by regulating gene expression through post transcriptional mechanisms. MicroRNAs, such as miR-26a and miR-132, have been investigated as novel biomarkers for diagnosis, prognosis, monitoring of therapeutic response, and therapeutic targets in ovarian carcinomas. Some long non-coding RNAs, such as H19 and UCA1, may be involved in the pathogenesis of ovarian carcinomas. MicroRNA and long non-coding RNA have potential clinical utility in the diagnosis of ovarian cancer and predicting prognosis, metastasis, recurrence, and response to therapy. PMID- 27673408 TI - microRNA-372 Suppresses Migration and Invasion by Targeting p65 in Human Prostate Cancer Cells. AB - Prostate cancer (PCa) is one of the most prevalent malignant tumors. microRNAs (miRNAs) play an important role in cancer initiation, progression, and metastasis, and their roles in PCa are becoming more apparent. In this study, we found that microRNA-372 (miR-372) is downregulated in human PCa and inhibits the proliferation activity, migration, and invasion of DU145 cells. Subsequently, p65 is confirmed as a target of miR-372, and knockdown of p65 expression similarly resulted in decreased proliferation activity, migration, and invasion. CDK8, MMP 9, and prostate-specific antigen were involved in both these processes. Taken together, our results show evidence that miR-372 may function as a tumor suppressor gene by regulating p65 in PCa and may provide a strategy for blocking PCa metastasis. PMID- 27673410 TI - Inhibitory Kinetics and Mechanism of Flavonoids Extracted from Cotinus coggygria Scop. Against Glioblastoma Cancer. AB - This proposal seeks to study the potential therapeutic modality of chemoprevention and anticancer effects and mechanisms of the flavonoids from Cotinus coggygria Scop. on glioblastoma cancer. In the current study, the total flavonoids (TFs) isolated from Cotinus coggygria Scop. var. cinerea Engl. (Cotinus coggygria Scop.) and the major flavonoids of Cotinus coggygria Scop. (CCFs) were identified, and the inhibitory kinetics of TF and CCF on glioblastoma cell lines were calculated. We also investigated whether TF or CCF regulated the apoptotic mechanism in cellular models of glio-blastoma cells. Finally, we evaluated whether treatment with TF or CCF suppressed tumor growth and inhibited migration in orthotopic mouse models of glioblastoma in vivo. In this study, the CCFs were identified as rutin, myricetin, and fisetin. TF and CCF remarkably inhibited cell proliferation and downregulated the PI3K/Akt and ERK signaling pathway in glioblastoma cell lines. Furthermore, the mitochondrial caspase dependent cascade was regulated by TF and myricetin. In addition, TF and myricetin exhibited significant antitumor effects on glioblastoma in vivo. Taken together, these results suggest that phytochemical and biological data provide evidence for the active components in Cotinus coggygria, and that the TFs are responsible for the anticancer effects on glioblastoma cell growth via induction of apoptosis. In addition, the representative compound myricetin could provide a clinically relevant therapeutic opportunity. Therefore, our data strongly suggest that myricetin-deprived CCF can serve as a potent chemopreventive herbal medicine. PMID- 27673411 TI - Child and Adolescent Clinical Features Preceding Adult Suicide Attempts. AB - The objective of this study was to identify the predictive value of juvenile factors for adult suicidal behavior. We reviewed clinical records to compare factors identified in childhood and adolescence between adult suicidal versus nonsuicidal major affective disorder subjects. Suicide attempts occurred in 23.1% of subjects. Age-at-first-symptom was 14.2 vs. 20.2 years among suicidal versus nonsuicidal subjects (p < 0.0001). More prevalent in suicidal versus non-suicidal subjects by multivariate analysis were: depressive symptoms, hyper-emotionality, younger-at-first-affective-episode, family suicide history, childhood mood swings, and adolescence low self-esteem. Presence of one factor yielded a Bayesian sensitivity of 64%, specificity of 50%, and negative predictive power of 86%. Several juvenile factors were associated with adult suicidal behavior; their absence was strongly associated with a lack of adult suicidal behavior. PMID- 27673412 TI - Effect of Breast Milk Calcium and Fluidity on Breast Cancer Cells: An In Vitro Cell Culture Study. AB - AIM: The aims of this study were to investigate the effects of calcium at the same concentration as that found in human milk on the viability, proliferation, and adhesion of MCF-7 human breast ductal carcinoma cells by exposing them to calcium at the same frequency as in breastfeeding. MATERIALS AND METHODS: High concentration calcium was applied for 30 minutes every 4 hours for 24, 48, and 72 hours. Cell proliferation and viability were measured using a hemocytometer and the MTT cell viability assay. The effects of calcium treatment were evaluated by a comparison among a multiple-, single-dose calcium treatment, and a control group. RESULTS: We show that calcium at the same concentration as that in milk caused a decrease in the number of cells but did not affect cell viability. CONCLUSIONS: The results of this study suggest that calcium caused a lowering of the number of cells from the luminal surface of the breast by triggering proliferation under the condition of fluidity. Calcium and fluidity together serve to eliminate breast cancer stem cells during the lactation period. Effects of the other components of milk can be analyzed by the new method developed in this study. PMID- 27673413 TI - Vitreous Cryopreservation of Human Umbilical Vein Endothelial Cells with Low Concentration of Cryoprotective Agents for Vascular Tissue Engineering. AB - Cryopreservation of human umbilical vein endothelial cells (HUVECs) is important to tissue engineering applications and the study of the role of endothelial cells in cardiovascular and cerebrovascular diseases. The traditional methods for cryopreservation by vitrification (cooling samples to a cryogenic temperature without apparent freezing) using high concentration of cryoprotective agents (CPAs) and slow freezing are suboptimal due to the severe toxicity of high concentration of CPAs and ice formation-induced cryoinjuries, respectively. In this study, we developed a method to cryopreserve HUVECs by vitrification with low concentration of CPAs. This is achieved by optimizing the CPAs and using highly thermally conductive quartz capillary (QC) to contain samples for vitrification. The latter minimizes the thermal mass to create ultra-fast cooling/warming rates. Our data demonstrate that HUVECs can be vitrified in the QC using 1.4 mol/L ethylene glycol and 1.1 mol/L dimethyl sulfoxide with more than 90% viability. Moreover, this method significantly improves the attachment efficiency of the cryopreserved HUVECs. The attached cells post-cryopreservation proliferate similarly to fresh cells. Therefore, this study may provide an effective vitrification technique to bank HUVECs for vascular tissue engineering and other applications. PMID- 27673414 TI - 2016 Taipei Declaration for Prevention of Suffering. PMID- 27673415 TI - Current treatment of heart failure with reduction of left ventricular ejection fraction. AB - INTRODUCTION: Heart failure is the commonest cause of hospitalization and of rehospitalization This review paper is a comprehensive review of current treatment of heart failure in 2016. The target of this review is all health care professionals who treat patients with heart failure. Areas covered: This article discusses stages of heart failure, treatment of heart failure with general measures, and drug therapy with diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, aldosterone antagonists, isosorbide dinitrate plus hydralazine, digoxin, other neurohormonal antagonists, sacubitril/valsartan, calcium channel blockers, and ivabradine. This article also discusses treatment of heart failure with use of cardiac resynchronization therapy, implantable cardioverter-defibrillators, and surgical therapy, and management of end-stage heart failure. This paper was written after an extensive Medline search reviewing articles written from 1970 through May, 2016. Expert commentary: Our approach as physicians must emphasize prevention of heart failure as well as treating it. Risk factors for developing heart failure, especially hypertension, must be better controlled starting in childhood. I concur with the current heart failure treatment guidelines (Tables 1 and 2 in this paper). PMID- 27673417 TI - Distinct cytokine and chemokine patterns in chronic diabetic ulcers and acute wounds. PMID- 27673418 TI - Vital role of cultural and religious context on suicidal behavior. PMID- 27673416 TI - Cervantes and Quijote protect heterochromatin from aberrant recombination and lead the way to the nuclear periphery. AB - Repairing double-strand breaks (DSBs) is particularly challenging in heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination and chromosome rearrangements. In Drosophila cells, faithful homologous recombination (HR) repair of heterochromatic DSBs relies on a specialized pathway that relocalizes repair sites to the nuclear periphery before Rad51 recruitment. Here we show that HR progression is initially blocked inside the heterochromatin domain by SUMOylation and the coordinated activity of two distinct Nse2 SUMO E3 ligases: Quijote (Qjt) and Cervantes (Cerv). In addition, the SUMO-targeted ubiquitin ligase (STUbL) Dgrn, but not its partner dRad60, is recruited to heterochromatic DSBs at early stages of repair and mediates relocalization. However, Dgrn is not required to prevent Rad51 recruitment inside the heterochromatin domain, suggesting that the block to HR progression inside the domain and relocalization to the nuclear periphery are genetically separable pathways. Further, SUMOylation defects affect relocalization without blocking heterochromatin expansion, revealing that expansion is not required for relocalization. Finally, nuclear pores and inner nuclear membrane proteins (INMPs) anchor STUbL/RENi components and repair sites to the nuclear periphery, where repair continues. Together, these studies reveal a critical role of SUMOylation and nuclear architecture in the spatial and temporal regulation of heterochromatin repair and the protection of genome integrity. PMID- 27673419 TI - Quality improvement in pediatrics: past, present, and future. AB - Almost two decades ago, the landmark report "To Err is Human" compelled healthcare to address the large numbers of hospitalized patients experiencing preventable harm. Concurrently, it became clear that the rapidly rising cost of healthcare would be unsustainable in the long-term. As a result, quality improvement methodologies initially rooted in other high-reliability industries have become a primary focus of healthcare. Multiple pediatric studies demonstrate remarkable quality and safety improvements in several domains including handoffs, catheter-associated blood stream infections, and other serious safety events. While both quality improvement and research are data-driven processes, significant differences exist between the two. Research utilizes a hypothesis driven approach to obtain new knowledge while quality improvement often incorporates a cyclic approach to translate existing knowledge into clinical practice. Recent publications have provided guidelines and methods for effectively reporting quality and safety work and improvement implementations. This review examines not only how quality improvement in pediatrics has led to improved outcomes, but also looks to the future of quality improvement in healthcare with focus on education and collaboration to ensure best practice approaches to caring for children. PMID- 27673420 TI - Therapeutic hypothermia translates from ancient history in to practice. AB - Acute postasphyxial encephalopathy around the time of birth remains a major cause of death and disability. The possibility that hypothermia may be able to prevent or lessen asphyxial brain injury is a "dream revisited". In this review, a historical perspective is provided from the first reported use of therapeutic hypothermia for brain injuries in antiquity, to the present day. The first uncontrolled trials of cooling for resuscitation were reported more than 50 y ago. The seminal insight that led to the modern revival of studies of neuroprotection was that after profound asphyxia, many brain cells show initial recovery from the insult during a short "latent" phase, typically lasting ~6 h, only to die hours to days later during a "secondary" deterioration phase characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Studies designed around this conceptual framework showed that mild hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration to allow the secondary deterioration to resolve, is associated with potent, long-lasting neuroprotection. There is now compelling evidence from randomized controlled trials that mild induced hypothermia significantly improves intact survival and neurodevelopmental outcomes to midchildhood. PMID- 27673421 TI - Does prenatal stress alter the developing connectome? AB - Human neurodevelopment requires the organization of neural elements into complex structural and functional networks called the connectome. Emerging data suggest that prenatal exposure to maternal stress plays a role in the wiring, or miswiring, of the developing connectome. Stress-related symptoms are common in women during pregnancy and are risk factors for neurobehavioral disorders ranging from autism spectrum disorder, attention deficit hyperactivity disorder, and addiction, to major depression and schizophrenia. This review focuses on structural and functional connectivity imaging to assess the impact of changes in women's stress-based physiology on the dynamic development of the human connectome in the fetal brain. PMID- 27673422 TI - Fifty years of brain imaging in neonatal encephalopathy following perinatal asphyxia. AB - In the past brain imaging of term infants with hypoxic-ischemic encephalopathy (HIE) was performed with cranial ultrasound (cUS) and computed tomography (CT). Both techniques have several disadvantages sensitivity and specificity is limited compared with magnetic resonance imaging (MRI) and CT makes use of radiation. At present MRI including diffusion weighted MRI during the first week of life, has become the method of choice for imaging infants with HIE. In addition to imaging, blood vessels and blood flow can be visualized using MR angiography, MR venography, and arterial spin labeling. Since the use of these techniques additional lesions in infants with HIE, such as arterial ischemic stroke, sinovenous thrombosis, and subdural hemorrhages can be diagnosed, and the incidence appears to be higher than shown previously. Phosphorus magnetic resonance spectroscopy (MRS) has led to the concept of secondary energy failure in infants with HIE, but has not been widely used. Proton MRS of the basal ganglia and thalamus is one of the best predictors of neurodevelopmental outcome. cUS should still be used for screening infants admitted to a NICU with neonatal encephalopathy. In the future magnetic resonance techniques will be increasingly used as early biomarkers of neurodevelopmental outcome in trials of neuroprotective strategies. PMID- 27673424 TI - Drugs, guns and cars: how far we have come to improve safety in the United States; yet we still have far to go. AB - Significant breakthroughs in the field of injury prevention and childhood safety have occurred during the past half-century. For example, the Poison Prevention Packaging Act of 1970 and the institution of child passenger safety laws are responsible for a significant reduction in injuries among children and adolescents. This review will focus on the following three topics because of their significant contribution to pediatric injury morbidity, especially among adolescents, and their promise for further effective prevention research. Opioid overdoses by adolescents and young adults are increasing; however, the use of naloxone by bystanders represents a life-saving development in opioid overdose prevention that deserves further investigation. Youth firearm injury remains a major cause of death and disability in adolescents. Despite a lack of robust injury prevention research on the topic, the development of novel approaches to access and examine firearm injury data is leading to exploration of public health approaches to reduce these injuries. Finally, despite legislative and educational efforts surrounding child passenger safety and graduated driver license laws, motor vehicle crashes are still a leading cause of injury for both children and adolescents; however, research on these laws holds the opportunity for significant reduction in injuries. Focused efforts to reduce unintentional injuries from opiate overdoses, firearms and motor vehicle crashes may produce a breakthrough in the field of injury prevention similar to that of the Poison Prevention Packaging Act. PMID- 27673423 TI - Congenital central hypoventilation syndrome: a bedside-to-bench success story for advancing early diagnosis and treatment and improved survival and quality of life. AB - The "bedside-to-bench" Congenital Central Hypoventilation Syndrome (CCHS) research journey has led to increased phenotypic-genotypic knowledge regarding autonomic nervous system (ANS) regulation, and improved clinical outcomes. CCHS is a neurocristopathy characterized by hypoventilation and ANS dysregulation. Initially described in 1970, timely diagnosis and treatment remained problematic until the first large cohort report (1992), delineating clinical presentation and treatment options. A central role of ANS dysregulation (2001) emerged, precipitating evaluation of genes critical to ANS development, and subsequent 2003 identification of Paired-Like Homeobox 2B (PHOX2B) as the disease-defining gene for CCHS. This breakthrough engendered clinical genetic testing, making diagnosis exact and early tracheostomy/artificial ventilation feasible. PHOX2B genotype-CCHS phenotype relationships were elucidated, informing early recognition and timely treatment for phenotypic manifestations including Hirschsprung disease, prolonged sinus pauses, and neural crest tumors. Simultaneously, cellular models of CCHS-causing PHOX2B mutations were developed to delineate molecular mechanisms. In addition to new insights regarding genetics and neurobiology of autonomic control overall, new knowledge gained has enabled physicians to anticipate and delineate the full clinical CCHS phenotype and initiate timely effective management. In summary, from an initial guarantee of early mortality or severe neurologic morbidity in survivors, CCHS children can now be diagnosed early and managed effectively, achieving dramatically improved quality of life as adults. PMID- 27673427 TI - Nanomolar Binding of Steroids to Cucurbit[n]urils: Selectivity and Applications. AB - Cucurbit[n]urils (CBn, n = 7, 8) serve as artificial receptors for steroids (21 tested), including the hormones testosterone and estradiol as well as steroidal drugs. Fluorescence displacement titrations and isothermal titration calorimetry (ITC) provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors. Remarkable binding selectivities, even for homologous steroid pairs, were investigated in detail by NMR, X-ray crystal diffraction, ITC, and quantum chemical calculations. Notably, the CBn*steroid complexes are stable in water and buffers, in artificial gastric acid, and even in blood serum. Numerous applications have been demonstrated, which range from the solubility enhancement of the steroids in the presence of the macrocycles (up to 100 times, for drug delivery) and the principal component analysis of the fluorescence responses of different CBn*reporter dye combinations (for differential sensing of steroids) to the real-time monitoring of chemical conversions of steroids as substrates (for enzyme assays). PMID- 27673426 TI - Respiratory Manifestations of Hypothyroidism: A Systematic Review. AB - BACKGROUND: Hypothyroidism has been associated with increased pulmonary morbidity and overall mortality. A systematic review was conducted to identify the prevalence and underlying mechanisms of respiratory problems among patients with thyroid insufficiency. METHODS: PubMed and EMBASE databases were searched for relevant literature from January 1950 through January 2015 with the following study eligibility criteria: English-language publications; adult subclinical or overt hypothyroid patients; intervention, observational, or retrospective studies; and respiratory manifestations. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement was followed, and Cochrane's risk of bias tool was used. RESULTS: A total of 1699 papers were screened by two independent authors for relevant titles. Of 109 relevant abstracts, 28 papers underwent full-text analyses, of which 22 were included in the review. Possible mechanisms explaining respiratory problems at multiple physiological levels were identified, such as the ventilator control system, diaphragmatic muscle function, pulmonary gas exchange, goiter caused upper airway obstruction, decreased capacity for energy transduction, and reduced glycolytic activity. Obstructive sleep apnea syndrome was found among 30% of newly diagnosed patients with overt hypothyroidism, and demonstrated reversibility following treatment. The evidence for or against a direct effect on pulmonary function was ambiguous. However, each of the above-mentioned areas was only dealt with in a limited number of studies. Therefore, it is not possible to draw any strong conclusions on any of these themes. Moreover, most studies were hampered by considerable risk of bias due for example to small numbers of patients, lack of control groups, randomization and blinding, and differences in body mass index, sex, and age between subjects and controls. CONCLUSION: Mechanistic data linking hypothyroidism and respiratory function are at best limited. This area of research is therefore open for retesting hypotheses, using appropriate study designs and methods. PMID- 27673425 TI - Treatment of perinatal viral infections to improve neurologic outcomes. AB - Viral infections in the fetus or newborn often involve the central nervous system (CNS) and can lead to significant morbidity and mortality. Substantial progress has been made in identifying interventions decreasing adverse neurodevelopmental outcomes in this population. This review highlights progress in treatment of important viruses affecting the CNS in these susceptible hosts, focusing on herpes simplex virus (HSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and enteroviruses. The observation that high-dose acyclovir improves mortality in neonatal HSV disease culminated decades of antiviral research for this disease. More recently, prolonged oral acyclovir was found to improve neurologic morbidity after neonatal HSV encephalitis. Ganciclovir, and more recently its oral prodrug valganciclovir, is effective in improving hearing and neurodevelopment after congenital CMV infection. Increasing evidence suggests early control of perinatal HIV infection has implications for neurocognitive functioning into school age. Lastly, the antiviral pleconaril has been studied for nearly two decades for treating severe enteroviral infections, with newer data supporting a role for this drug in neonates. Identifying common mechanisms for pathogenesis of viral CNS disease during this critical period of brain development is an important research goal, highlighted by the recent emergence of Zika virus as a potential cause of fetal neurodevelopmental abnormalities. PMID- 27673428 TI - High-Mobility Group Box 1 (HMGB1) Is Elevated Systemically in Persons with Acute or Chronic Traumatic Spinal Cord Injury. AB - Inflammation in traumatic spinal cord injury (SCI) has been proposed to promote damage acutely and oppose functional recovery chronically. However, we do not yet understand the signals that initiate or prolong inflammation in persons with SCI. High-Mobility Group Box 1 (HMGB1) is a potent systemic inflammatory cytokine-or damage-associated molecular pattern molecule (DAMP)-studied in a variety of clinical settings. It is elevated in pre-clinical models of traumatic spinal cord injury (SCI), where it promotes secondary injury, and strategies that block HMGB1 improve functional recovery. To investigate the potential translational relevance of these observations, we measured HMGB1 in plasma from adults with acute (<= 1 week post-SCI, n = 16) or chronic (>= 1 year post-SCI, n = 47) SCI. Plasma from uninjured persons (n = 51) served as controls for comparison. In persons with acute SCI, average HMGB1 levels were significantly elevated within 0-3 days post injury (6.00 +/- 1.8 ng/mL, mean +/- standard error of the mean [SEM]) or 4-7 (6.26 +/- 1.3 ng/mL, mean +/- SEM), compared with controls (1.26 +/- 0.24 ng/mL, mean +/- SEM; p <= 0.001 and p <= 0.01, respectively). In persons with chronic SCI who were injured for 15 +/- 1.5 years (mean +/- SEM), HMGB1 also was significantly elevated, compared with uninjured persons (3.7 +/- 0.69 vs. 1.26 +/ 0.24 ng/mL, mean +/- SEM; p <= 0.0001). Together, these data suggest that HMGB1 may be a common, early, and persistent danger signal promoting inflammation in individuals with SCI. PMID- 27673429 TI - Prevalence of anti-hepatitis C virus antibody among pregnant women and blood donors at Bowen University Teaching Hospital, Ogbomoso, Oyo State, Nigeria. AB - Hepatitis C virus is one of the emerging infectious diseases that can be transmitted through blood-to-blood contact. This study was carried out to determine the prevalence of anti-HCV antibodies among potential blood donors and pregnant women attending Bowen University Teaching Hospital (BUTH), Ogbomoso, Oyo State. This hospital-based study was conducted from December 2014 to September 2015. The study group (N = 279) included potential blood donors and pregnant women. Data on socio-demographic characteristics and potential risk factors were collected using a structured questionnaire. The presence of anti-HCV antibodies in serum samples of the studied subjects were detected using third-generation Enzyme Linked Immunosorbent Assay (ELISA) (WKEA Med Supplies Corp, China). Chisquare test was utilized to assess the association between the socio demographic variables and HCV status. Logistic regression was done to determine the strength of association between risk factors and HCV status. Statistical significance was set at P ? 0.05. Overall seroprevalence of hepatitis C virus infection was found to be 1.79% consisting 0.36% of pregnant women and 1.43% of blood donors. None of the socio-demographic characteristics and potential risk factors among the study groups were significantly associated with hepatitis C virus infection. This study found a seroprevalence of anti-HCV antibody to be 1.79%, thus, screening of pregnant women and blood donors for HCV infections with the use of ELISA is recommended because of its important role in detecting the presence of anti-HCV antibody with utmost specificity and sensitivity. PMID- 27673431 TI - Unveiling the Semicoherent Interface with Definite Orientation Relationships between Reinforcements and Matrix in Novel Al3BC/Al Composites. AB - High-strength lightweight Al-based composites are promising materials for a wide range of applications. To provide high performance, a strong bonding interface for effective load transfer from the matrix to the reinforcement is essential. In this work, the novel Al3BC reinforced Al composites have been in situ fabricated through a liquid-solid reaction method and the bonding interface between Al3BC and Al matrix has been unveiled. The HRTEM characterizations on the Al3BC/Al interface verify it to be a semicoherent bonding structure with definite orientation relationships: (0001)Al3BC//(111)Al;[1120]Al3BC//[011]Al. Periodic arrays of geometrical misfit dislocations are also observed along the interface at each (0001)Al3BC plane or every five (111)Al planes. This kind of interface between the reinforcement and the matrix is strong enough for effective load transfer, which would lead to the evidently improved strength and stiffness of the introduced new Al3BC/Al composites. PMID- 27673430 TI - Can filling phase urodynamic parameters predict the success of the bulbar artificial urinary sphincter in treating post-prostatectomy incontinence? AB - OBJECTIVE: To evaluate whether filling phase urodynamic parameters can predict the success of the artificial urinary sphincter (AUS) in treating post prostatectomy incontinence (PPI). MATERIALS AND METHODS: We reviewed the pre-AUS urodynamics of 99 patients with PPI at two tertiary referral centers. We documented the peak DO pressure (Pdet ), capacity, and compliance (C). We defined success as patient-reported continence or only using one safety pad. Patients' perception of improvement was assessed using the PGI-I score. RESULTS: Sixty eight percent (n = 68) of patients had a successful outcome. The mean compliance for the "success" and "failure" group was 112.3 mL/cmH2 O (+/-119.7) and 34.1 mL/cmH2 O (+/-36.2), respectively. Fifty-five percent (17/31) of patients in the "failure" group demonstrated DO(Pdet = 36.2 +/- 18.2 cmH2 O) compared to 18% (12/68) in the success group. The differences between the two groups in Pdet and compliance were statistically significant (all P < 0.01). There was, however, no statistical difference between the mean cystometric capacities of patients in the two outcome groups. Thirteen out of 18 (72%) patients who had radiotherapy had a poor outcome ("success" group only 15% [9/59]). These results were used to develop a nomogram for the probability of AUS success. A good inverse correlation (r = -0.65) was demonstrated between the probability of AUS success as deduced from the nomogram and PGI-I score post-AUS implantation CONCLUSION: Compliance and Pdet are predictors of outcome following AUS implantation for PPI. We have developed and internally validated a nomogram that may be used to determine an individualized likelihood of AUS success. This nomogram may be used as a counseling tool to objectively set realistic expectations of continence post-AUS implantation. PMID- 27673432 TI - l-alpha-Phosphatidylglycerol Chlorohydrins as Potential Biomarkers for Chlorine Gas Exposure. AB - Chlorine is a widely available toxic chemical that has been repeatedly used in armed conflict globally. The Organization for the Prohibition of Chemical Weapons (OPCW) have on numerous occasions found "compelling confirmation" that chlorine gas has been used against civilians in northern Syria. However, currently, there are no analytical methods available to unambiguously prove chlorine gas exposure. In this study, we describe the screening for chlorinated biomolecules by the use of mass isotope ratio filters followed by the identification of two biomarkers present in bronchoalveolar lavage fluid (BALF) from chlorine gas exposed mice. The relevance of these markers for human exposure was verified by their presence in in vitro chlorinated human BALF. The biomarkers were detectable for 72 h after exposure and were absent in nonexposed control animals. Furthermore, the biomarkers were not detected in humans diagnosed with chronic respiratory diseases. The potential chlorine specific markers were all chlorohydrins of unsaturated pulmonary surfactant phospholipids; phosphatidylglycerols, and phosphatidylcholines. Mass spectrometry fragmentation characteristics were favorable for the phosphatidylglycerol chlorohydrins, and they were therefore proposed as the best biomarker candidates. PMID- 27673433 TI - Correction to "Organocatalytic Enantioselective Intramolecular Oxa-Michael Reaction of Enols: Synthesis of Chiral Isochromene". PMID- 27673434 TI - Novel Dimer Compounds That Bind alpha-Synuclein Can Rescue Cell Growth in a Yeast Model Overexpressing alpha-Synuclein. A Possible Prevention Strategy for Parkinson's Disease. AB - The misfolding of alpha-synuclein is a critical event in the death of dopaminergic neurons and the progression of Parkinson's disease. Previously, it was suggested that drugs, which bind to alpha-synuclein and form a loop structure between the N- and C-termini, tend to be neuroprotective, whereas others, which cause a more compact structure, tend to be neurotoxic. To improve the binding to alpha-synuclein, eight novel compounds were synthesized from a caffeine scaffold attached to (R,S)-1-aminoindan, (R,S)-nicotine, and metformin, and their binding to alpha-synuclein determined through nanopore analysis and isothermal titration calorimetry. The ability of the dimers to interact with alpha-synuclein in a cell system was assayed in a yeast model of PD which expresses an AS-GFP (alpha synuclein-Green Fluorescent Protein) construct under the control of a galactose promoter. In 5 mM galactose this yeast strain will not grow and large cytoplasmic foci are observed by fluorescent microscopy. Two of the dimers, C8-6-I and C8-6 N, at a concentration of 0.1 MUM allowed the yeast to grow normally in 5 mM galactose and the AS-GFP became localized to the periphery of the cell. Both dimers were superior when compared to the monomeric compounds. The presence of the dimers also caused the disappearance of preformed cytoplasmic foci. Nanopore analysis of C8-6-I and C8-6-N were consistent with simultaneous binding to both the N- and C-terminus of alpha-synuclein but the binding constants were only 105 M-1. PMID- 27673435 TI - Behavior Therapy for Youth With Tourette Disorder. AB - Persistent tic disorders and Tourette disorder (TD) are neuropsychiatric conditions that commonly co-occur among youth with obsessive-compulsive disorder. Although historically managed with pharmacological agents such as antipsychotics and alpha-2 agonists, behavioral interventions like habit reversal training (HRT) and the comprehensive behavioral intervention for tics have demonstrated considerable efficacy in reducing tic symptom severity. This case study illustrates the implementation of behavior therapy in reducing tic symptom severity of an adolescent with TD. Arlene was a 14-year-old girl with TD who presented with moderate tic symptom severity that caused her physical, academic, and social impairment. In addition to concurrent pharmacotherapy, Arlene completed a 20-session weekly course of HRT, and experienced a clinically meaningful reduction in tic symptom severity and tic-related impairment. This example provides further evidence of the benefit of behavior therapy in reducing tic symptom severity and highlights key considerations for treatment of youth with TD. PMID- 27673436 TI - Vitamin D Status of Older Adults with Dynapenic Obesity in Ecuador. PMID- 27673437 TI - Sleep quality outcomes after medical and surgical management of chronic rhinosinusitis. AB - BACKGROUND: Endoscopic sinus surgery (ESS) has been shown to improve sleep in patients with chronic rhinosinusitis (CRS). However, it is unknown how this improvement compares with non-CRS control subjects' sleep, and medically treated CRS patients. METHODS: Patients meeting diagnostic criteria for CRS and controls from the same reference population were recruited from 4 academic centers. Patients chose either medical or surgical treatment. The Pittsburgh Sleep Quality Index (PSQI) was administered to patients before treatment and after 6 months, whereas controls received the PSQI at enrollment. RESULTS: The study population consisted of 187 cases (64 medical and 123 surgical) and 101 controls. Baseline PSQI scores for CRS patients (9.27 +/- 4.76) were worse than for controls (5.78 +/- 3.25), even after controlling for potential confounding factors such as asthma and allergy (p < 0.001). There was no significant difference in baseline PSQI between patients choosing medical vs surgical treatment. The PSQI score in surgical patients improved from 8.36 +/- 5.05 to 7.44 +/- 5.09 (p = 0.020). The PSQI score in medical patients demonstrated a nonsignificant increase with treatment from 8.71 +/- 4.48 to 9.06 +/- 4.80 (p = 0.640). After controlling for allergy and asthma, 6-month PSQI scores in medical patients remained significantly higher than in controls (p = 0.001), whereas a significant difference could not be demonstrated between surgical patients and controls (p > 0.05). PSQI subdomain analysis mirrored the overall findings. CONCLUSION: Patients with CRS report worse sleep compared with controls. Surgically treated CRS patients show significant improvement in PSQI scores, whereas those continuing with medical management fail to improve and remain worse than controls. PMID- 27673438 TI - Adjuvant chemotherapy may improve disease-free survival in patients with rectal cancer positive for MRI-detected extramural venous invasion following chemoradiation. AB - AIM: MRI-detected extramural venous invasion (mrEMVI) is a poor prognostic factor in rectal cancer. Preoperative chemoradiotherapy (CRT) can cause regression in the severity of EMVI and subsequently improve survival whereas mrEMVI persisting after CRT confers an increased risk of recurrence. The effect of adjuvant chemotherapy (AC) following CRT on survival in rectal cancer remains unclear. The aim of this study was to determine whether there is a survival advantage for AC given to patients with mrEMVI persisting after CRT. METHOD: A prospective analysis was conducted of consecutive patients with locally advanced rectal cancer between 2006 and 2013. All patients underwent CRT followed by surgery. AC was given to selected patients based on the presence of specific 'high-risk' features. Comparison was made between patients offered AC with observation alone. The primary outcome was 3-year disease-free survival (DFS). RESULTS: Of 631 patients, 227 (36.0%) demonstrated persistent mrEMVI following CRT. Patients were grouped on the basis of AC or observation and were matched for age, performance status and final histopathological staging. Three-year DFS in the AC group was 74.6% compared with 53.7% in the observation only group. AC had a survival benefit on multivariate analysis (hazard ratio 0.458; 95% CI: 0.271-0.775, P = 0.004). CONCLUSION: Patients with persistent mrEMVI following CRT who receive AC may have a decreased risk of recurrence and an improved 3-year DFS compared with patients not receiving AC, irrespective of age and performance status. PMID- 27673439 TI - N2 non-thermal atmospheric pressure plasma promotes wound healing in vitro and in vivo: Potential modulation of adhesion molecules and matrix metalloproteinase-9. AB - Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N2 optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment. We also showed that NTP treatment increased Slug and TCF8/ZEB1 expression and decreased that of E-cadherin, suggesting induction of the epithelial-to-mesenchymal transition (EMT). The effect of N2 NTP was verified on rat wound model. Taken together, these results suggest that N2 NTP promotes wound healing by inducing the EMT and activating the MMP-9/uPA system. These findings show the therapeutic potential of NTP for skin wound healing. PMID- 27673441 TI - Triple-Stranded Cluster Helicates for the Selective Catalytic Oxidation of C-H Bonds. AB - Triple-stranded cluster helicates with heptametallic dicubane cores are synthesized by entrapping metals in the cavities of linear triple helicates based on a C2-symmetrical hexadentate Schiff-base ligand of ortho-substitued biphenol. The helicates are stable in both the solution and solid states, and the copper species could selectively catalyze the oxidation of C-H bonds of alkanes to ketones. PMID- 27673440 TI - Buparlisib, a PI3K inhibitor, demonstrates acceptable tolerability and preliminary activity in a phase I trial of patients with advanced leukemias. AB - Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day. The MTD was 80 mg/day. Of the 14 patients treated, the best response was stable disease in one patient that lasted 82 days. The median survival for all patients was 75 days (range 10 568). Three patients with a 3q26 chromosome abnormality had a significantly improved median survival of 360 days (range 278-568) as compared to a median survival of 57 days (range, 10-125) among the 11 other patients. The most frequent drug-related toxicities included confusion, mucositis, dysphagia, and fatigue. Western blot profiling revealed a decrease in p-pS6K/total pS6K in 5/7 (71%) available patient samples with a mean quantitative inhibition of 65% (range, 32-100%) and a decrease in p-FOXO3/total FOXO3 in 4/6 (67%) samples with a mean quantitative inhibition of 93% (range, 89-100%). BKM120 administered at 80 mg/day showed modest efficacy and was tolerable in advanced acute leukemias. Am. J. Hematol. 92:7-11, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27673442 TI - Effects of Functional Disability and Depressive Symptoms on Mortality in Older Mexican-American Adults with Diabetes Mellitus. AB - OBJECTIVES: To examine the effect of co-occurring depressive symptoms and functional disability on mortality in older Mexican-American adults with diabetes mellitus. DESIGN: Longitudinal cohort study. SETTING: Hispanic Established Populations for the Epidemiological Study of the Elderly (HEPESE) survey conducted in the southwestern United States (Texas, Colorado, Arizona, New Mexico, California). PARTICIPANTS: Community-dwelling Mexican Americans with self reported diabetes mellitus participating in the HEPESE survey (N = 624). MEASUREMENTS: Functional disability was assessed using a modified version of the Katz activity of daily living scale. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Mortality was determined by examining death certificates and reports from relatives. Cox proportional hazards regression analyses were used to examine the hazard of mortality as a function of co-occurring depressive symptoms and functional disability. RESULTS: Over a 9.2 year follow-up, 391 participants died. Co-occurring high depressive symptoms and functional disability increased the risk of mortality (hazard ratio (HR) = 3.02, 95% confidence interval (CI) = 2.11-4.34). Risk was greater in men (HR = 8.11, 95% CI = 4.34-16.31) than women (HR = 2.21, 95% CI = 1.42-3.43). CONCLUSION: Co occurring depressive symptoms and functional disability in older Mexican-American adults with diabetes mellitus increases mortality risk, especially in men. These findings have important implications for research, practice, and public health interventions. PMID- 27673443 TI - Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96 Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. AB - Tenofovir disoproxil fumarate is associated with renal and bone toxicity. In a single-arm, open-label study of 242 virologically suppressed, HIV-infected participants with creatinine clearance 30-69 mL/min who switched to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, participants had stable creatinine clearance, significant and durable improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001), and significant increases in hip and spine bone mineral density through 96 weeks (P < 0.001). Eighty-eight percent maintained HIV-1 RNA <50 c/mL at week 96. These longer-term results support the use of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-infected individuals with mild-moderately impaired renal function. PMID- 27673444 TI - Functionalization of Active Ester-Based Polymersomes for Enhanced Cell Uptake and Stimuli-Responsive Cargo Release. AB - Poly(2,3-dihydroxypropyl methacrylamide) (P(DHPMA))-based amphiphilic block copolymers have recently proven to form polymer vesicles (polymersomes). In this work, we further expand their potential by incorporating (i) units for pH dependent disintegration into the hydrophobic membrane and (ii) mannose as targeting unit into the hydrophilic block. This last step relies on the use of an active ester prepolymer. We confirm the stability of the polymersomes against detergents like Triton X-100 and their low cytotoxicity. The incorporation of 2 (2,2-dimethyl-1,3-dioxolane-4-yl)ethyl methacrylate into the hydrophobic block (lauryl methacrylate) allows a pH-responsive disintegration for cargo release. Efficient decomposition of the polymersome structure is monitored by dynamic light scattering. It is thus possible to include an active enzyme (glucose oxidase), which gets only active (is set free) after vesicle disintegration. In addition, the introduction of mannose as targeting structure allows enhanced and selective targeting of dendritic cells. PMID- 27673445 TI - Physical and biological characterization of sericin-loaded copolymer liposomes stabilized by polyvinyl alcohol. AB - Sericin protein (SP) is widely used as a nutrient biomaterial for biomedical and cosmeceutical applications although it shows low stability to heat and light. To overcome these problems and add value to wastewater from the silk industry, sericin protein was recovered as sericin-loaded copolymer-liposomes (SP-PVA-LP), prepared through thin film hydration. The size and morphology of the liposomes were investigated using dynamic light scattering (DLS), and electron microscopy (SEM and TEM). The particle size, liposome surface morphology and encapsulation efficiency of SP were dependent on PVA concentration. The hydrodynamic size of the nanoparticles was between 200 and 400nm, with the degree of negative charge contingent on sericin loading. SEM and TEM images confirmed the mono-dispersity, and spherical nature of the particles, with FTIR measurements confirming the presence of surface bound PVA. Exposure of liposomes to 500ppm sericin highlighted a dependence of encapsulation efficiency on PVA content; 2% surface PVA proved the optimal level for sericin loading. Cytotoxicity and viability assays revealed that SP-loaded surface modified liposomes promote cellular attachment and proliferation of human skin fibroblasts without adverse toxic effects. Surface modified copolymer liposomes show high performance in maintaining structural stability, and promoting enhancements in the solubility and bio-viability of sericin. Taken together, these biocompatible constructs allow for effective controlled release, augmenting sericin activity and resulting in effective drug delivery systems. PMID- 27673447 TI - Corrigendum to "Citric acid crosslinked cyclodextrin/hydroxypropylmethylcellulose hydrogel films for hydrophobic drug delivery" [Int. J. Biol. Macromol. 93 (2016) 75-86]. PMID- 27673446 TI - Competition between bacteria and phosphate for adsorption sites on gibbsite: An in-situ ATR-FTIR spectroscopic and macroscopic study. AB - Sorption and desorption of phosphate (P) on Fe and Al (hydr)oxides may be affected by bacteria in soils because their ubiquitous and strong interactions. The role of Bacillus subtilis and Pseudomonas fluorescens in adsorption of P on gibbsite (gamma-AlOOH) was systematically investigated under a wide range of conditions by combining in-situ attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy with batch macroscopic experiments. In-situ ATR FTIR observations of the ternary systems (bacteria, P, and gibbsite) showed simultaneous desorption of P from, and adhesion of the bacteria to, gibbsite, indicating a competition between the two for surface sites. Batch desorption experiments showed that bacteria could mobilize the P from gibbsite into solution, and macroscopic adsorption data showed that the amount of P adsorbed on the bacteria-gibbsite complex was less than that on gibbsite alone over durations from 0h to 26h, concentrations of P from 0.1mM to 2.0mM, pH from 5 to 8, and ionic strength from 0M to 0.5M, suggesting that bacteria inhibit the adsorption of P on gibbsite. The degree of inhibition increased with the number of bacteria in the system and was significantly but non-linearly correlated with the decline in the positive charge on gibbsite induced by the bacteria. Therefore, competition for suitable sites on the surface of gibbsite between P and the bacteria and reduction in the positive charge on the surface of gibbsite induced by bacteria are proposed as two important mechanisms that inhibit P adsorption. These findings highlight the role of bacteria in regulating the availability of P to plants and its mobility in natural environments. PMID- 27673448 TI - Generalized Langevin Methods for Calculating Transmembrane Diffusivity. AB - The membrane permeability coefficient of a solute can be estimated using the solubility-diffusion model. This model requires the diffusivity profile (D(z)) of the solute as it moves along the transmembrane axis, z. The generalized Langevin equation provides one strategy for calculating position-dependent diffusivity from straightforward molecular dynamics simulations where the solute is restrained to a series of positions on the z-coordinate by a harmonic potential. The diffusivity of the solute is calculated from its correlation functions, which are related to the friction experienced by the solute. Roux and Hummer have derived expressions for the diffusion coefficient from the velocity autocorrelation function (VACF) and position autocorrelation function (PACF), respectively. In this work, these methods are validated by calculating the diffusivity of H2O and O2 in homogeneous liquids. These methods are then used to calculate transmembrane diffusivity profiles. The VACF method is less sensitive to thermostat forces and has incrementally lower errors but is more sensitive to the spring constant of the harmonic restraint. For the permeation of a solute through a lipid bilayer, the diffusion coefficients calculated using these methods provided significantly different results. Long-lived correlations of the restrained solute due to inhomogeneities in the bilayer can result in spuriously low diffusivity when using the PACF method. The method based on the VACF does not have this issue and predicts higher rates of diffusion inside the bilayer. PMID- 27673450 TI - ASPL-TFE3 Oncoprotein Regulates Cell Cycle Progression and Induces Cellular Senescence by Up-Regulating p21. AB - Alveolar soft part sarcoma is an extremely rare soft tissue sarcoma with poor prognosis. It is characterized by the unbalanced recurrent chromosomal translocation der(17)t(X;17)(p11;q25), resulting in the generation of an ASPL TFE3 fusion gene. ASPL-TFE3 oncoprotein functions as an aberrant transcriptional factor and is considered to play a crucial role in the tumorigenesis of alveolar soft part sarcoma. However, the underlying molecular mechanisms are poorly understood. In this study, we identified p21 (p21WAF1/CIP1) as a direct transcriptional target of ASPL-TFE3. Ectopic ASPL-TFE3 expression in 293 cells resulted in cell cycle arrest and significant increases in protein and mRNA levels of p21. ASPL-TFE3 activated p21 expression in a p53-independent manner through direct transcriptional interactions with the p21 promoter region. When ASPL-TFE3 was expressed in human bone marrow-derived mesenchymal stem cells in a tetracycline-inducible manner, we observed the up-regulation of p21 expression and the induction of senescence-associated beta-galactosidase activity. Suppression of p21 significantly decreased the induction of ASPL-TFE3-mediated cellular senescence. Furthermore, ASPL-TFE3 expression in mesenchymal stem cells resulted in a significant up-regulation of proinflammatory cytokines associated with senescence-associated secretory phenotype (SASP). These results show that ASPL-TFE3 regulates cell cycle progression and induces cellular senescence by up regulating p21 expression. In addition, our data suggest a potential mechanism by which ASPL-TFE3-induced senescence may play a role in tumorigenesis by inducing SASP, which could promote the protumorigenic microenvironment. PMID- 27673451 TI - Care and society. PMID- 27673452 TI - Access to medicines-the status quo is no longer an option. PMID- 27673449 TI - Limitations in intense exercise performance of athletes - effect of speed endurance training on ion handling and fatigue development. AB - Mechanisms underlying fatigue development and limitations for performance during intense exercise have been intensively studied during the past couple of decades. Fatigue development may involve several interacting factors and depends on type of exercise undertaken and training level of the individual. Intense exercise (1/2-6 min) causes major ionic perturbations (Ca2+ , Cl- , H+ , K+ , lactate- and Na+ ) that may reduce sarcolemmal excitability, Ca2+ release and force production of skeletal muscle. Maintenance of ion homeostasis is thus essential to sustain force production and power output during intense exercise. Regular speed endurance training (SET), i.e. exercise performed at intensities above that corresponding to maximum oxygen consumption (VO2, max ), enhances intense exercise performance. However, most of the studies that have provided mechanistic insight into the beneficial effects of SET have been conducted in untrained and recreationally active individuals, making extrapolation towards athletes' performance difficult. Nevertheless, recent studies indicate that only a few weeks of SET enhances intense exercise performance in highly trained individuals. In these studies, the enhanced performance was not associated with changes in VO2, max and muscle oxidative capacity, but rather with adaptations in muscle ion handling, including lowered interstitial concentrations of K+ during and in recovery from intense exercise, improved lactate- -H+ transport and H+ regulation, and enhanced Ca2+ release function. The purpose of this Topical Review is to provide an overview of the effect of SET and to discuss potential mechanisms underlying enhancements in performance induced by SET in already well trained individuals with special emphasis on ion handling in skeletal muscle. PMID- 27673453 TI - Fit to serve. PMID- 27673454 TI - GEMS extend understanding of childhood diarrhoea. PMID- 27673455 TI - How the paediatric workforce can address the opioid crisis. PMID- 27673456 TI - Offline: A prescription for prosperity. PMID- 27673457 TI - Global Fund replenishment meeting nears target amount. PMID- 27673458 TI - EpiPen price hike comes under scrutiny. PMID- 27673459 TI - Jumping cultural hurdles to keep fit in the Middle East. PMID- 27673460 TI - Knowledge. PMID- 27673461 TI - Health-care provider as witness. PMID- 27673462 TI - Obituary. Thomas Babington Boulton. PMID- 27673463 TI - Sport and the city: midtown madness. PMID- 27673465 TI - Development of bicycle infrastructure for health and sustainability. PMID- 27673464 TI - China's challenges in promoting physical activity and fitness. PMID- 27673466 TI - Alcohol and the Sustainable Development Goals. PMID- 27673467 TI - Schizophrenia. PMID- 27673468 TI - Department of Error. PMID- 27673469 TI - Department of Error. PMID- 27673471 TI - Department of Error. PMID- 27673472 TI - Small Molecules-Big Data. AB - Quantum mechanics builds large-scale graphs (networks): the vertices are the discrete energy levels the quantum system possesses, and the edges are the (quantum-mechanically allowed) transitions. Parts of the complete quantum mechanical networks can be probed experimentally via high-resolution, energy resolved spectroscopic techniques. The complete rovibronic line list information for a given molecule can only be obtained through sophisticated quantum-chemical computations. Experiments as well as computations yield what we call spectroscopic networks (SN). First-principles SNs of even small, three to five atomic molecules can be huge, qualifying for the big data description. Besides helping to interpret high-resolution spectra, the network-theoretical view offers several ideas for improving the accuracy and robustness of the increasingly important information systems containing line-by-line spectroscopic data. For example, the smallest number of measurements necessary to perform to obtain the complete list of energy levels is given by the minimum-weight spanning tree of the SN and network clustering studies may call attention to "weakest links" of a spectroscopic database. A present-day application of spectroscopic networks is within the MARVEL (Measured Active Rotational-Vibrational Energy Levels) approach, whereby the transitions information on a measured SN is turned into experimental energy levels via a weighted linear least-squares refinement. MARVEL has been used successfully for 15 molecules and allowed to validate most of the transitions measured and come up with energy levels with well-defined and realistic uncertainties. Accurate knowledge of the energy levels with computed transition intensities allows the realistic prediction of spectra under many different circumstances, e.g., for widely different temperatures. Detailed knowledge of the energy level structure of a molecule coming from a MARVEL analysis is important for a considerable number of modeling efforts in chemistry, physics, and engineering. PMID- 27673473 TI - Effect of green and red light in lipid accumulation and transcriptional profile of genes implicated in lipid biosynthesis in Chlamydomonas reinhardtii. AB - Microalgae have the potential to accumulate triacylglycerols under different light spectra. In this work, Chlamydomonas reinhardtii was grown under white (400 700 nm), red (650 nm), and green (550 nm) lights. According to our results, red light (650 nm) has a positive effect in the microalgae growth and chlorophyll concentration. About the lipid content, the control culture (white light illuminated) reached a 4.4% of dry cell weight (dcw), whereas the culture grown at 550 nm showed an increase of 1.35-fold in the lipids accumulation (5.96% dcw). Interestingly, the most significant accumulation was found in the culture grown at 650 nm (14.78% dcw) which means 3.36-fold higher with respect to the white light-illuminated culture. The most abundant fatty acids found in lipid extracts obtained from the cultures under different light wavelength were palmitic (C16: 0), oleic (C18: 1n9), stearidonic (C18: 4), and linoleic (C18: 2), which are useful in the biodiesel production. Changes in gene expression in response to different wavelength illuminations were assessed; however, an in-depth analysis of a larger number of genes involved in lipid biosynthesis is necessary to fully explain the highest accumulation of lipids in the culture grown under red light. This approach will be useful to find a sustainable source of lipids for biodiesel production. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1404-1411, 2016. PMID- 27673470 TI - Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. AB - BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1.5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen attributable diarrhoeal burden was 89.3% (95% CI 83.2-96.0) at the population level, compared with 51.5% (48.0-55.0) in the original GEMS analysis. The top six pathogens accounted for 77.8% (74.6-80.9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42.5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38.9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation. PMID- 27673475 TI - Fine-tuning the expression of microRNA-155 controls acetaminophen-induced liver inflammation. AB - Treatment of acetaminophen (APAP) in overdose can cause a potentially serious and fatal liver injury. MicroRNA-155 (miR-155), a multifunctional microRNA, is known to mediate inflammatory responses via regulating various target genes. In this study, we aimed to study the role of miR-155 in APAP-induced liver injury, using miR-155-/- mice and miR-155 in vivo intervention. We noted that miR-155 expression was significantly increased in liver and blood after APAP treatment. Knockout of miR-155 deteriorated APAP-induced liver damage, with the elevated serum levels of AST and ALT. The levels of various inflammatory mediators, such as TNF-alpha and IL-6, were markedly augmented in livers in the absence of miR 155. Moreover, miR-155 deficiency aberrantly activated NF-kappa-B signaling via enhancing p65 and IKKepsilon expression. Finally, in vivo administration of miR 155 agomir attenuated APAP-induced liver damage, reduced the serum levels of AST and ALT, and dampened the NF-kB signaling. In conclusion, our data demonstrated that miR-155 protects the mice against APAP-induced liver damage via mediating NF KB signaling pathway, suggesting that miR-155 might be a potential pharmaceutic target for treatment of APAP-induced liver inflammation. PMID- 27673477 TI - The role of autophagy in the pathogenesis of systemic lupus erythematosus. AB - Autophagy is a highly conserved catabolic process, whereby unwanted cytoplasmic contents are enclosed by the double-membrane autophagosomes and delivered to the lysosomes for degradation. It is responsible for the recycling of nutrients and cellular components, thus playing a pivotal role in maintaining cellular homeostasis as well as cell survival during stress conditions. Perturbations in autophagy are implicated in multiple diseases, such as cancers and neuro degeneration diseases. Recent studies demonstrate that autophagy may participate in almost every step of immune responses, including pathogen recognition, antigen processing and presentation, immune cell development and function, and immunoregulation. The pathogenesis of some autoimmune diseases, such as multiple sclerosis and Crohn's disease, has been reported to be associated with dysregulated autophagy. Systemic lupus erythematosus (SLE) is a chronic, potentially fatal autoimmune disease, characterized by dysregulation of immune cells and production of autoantibodies that cause widespread tissue and organ damage. The pathogenesis of SLE remains unclear. With several single nucleotide polymorphisms (SNPs) in autophagy-related gene5 (ATG5) being linked to SLE susceptibility, more and more lines of evidence from animal model, cell biology, immunology, and genetics studies show that autophagy contributes to the occurrence, development, and severity of SLE. PMID- 27673476 TI - Clinical observation of lymphocyte active immunotherapy in 380 patients with unexplained recurrent spontaneous abortion. AB - PURPOSE: This study aims to investigate the clinical curative effect of lymphocyte active immunotherapy (LAI) on unexplained recurrent spontaneous abortion (RSA). METHODS: A total of 749 RSA patients who received medical service in our hospital from October 2009 to June 2013 were enrolled into this study. These patients were randomly divided into two groups: LAI group (treatment group) and routine progesterone for maintenance tocolysis group (control group). A comparative analysis on the pregnancy outcomes in these two groups was conducted. RESULTS: Abortion rate was significantly lower in the LAI group than in the control group (P<0.05). Furthermore, pregnancy success rates were 89.7% and 32.2% in patients who received LAI and routine progesterone for maintenance tocolysis, respectively, and the difference was statistically significant (P<0.05). CONCLUSION: Our analysis suggested that LAI can treat RSA effectively and has an excellent clinical effect. Furthermore, the detection of blocking antibodies showed a positive prediction on pregnancy outcome. PMID- 27673478 TI - Baby-led compared with scheduled (or mixed) breastfeeding for successful breastfeeding. AB - BACKGROUND: Baby-led breastfeeding is recommended as best practice in determining the frequency and duration of a breastfeed. An alternative approach is described as scheduled, where breastfeeding is timed and restricted in frequency and duration. It is necessary to review the evidence that supports current recommendations, so that women are provided with high-quality evidence to inform their feeding decisions. OBJECTIVES: To evaluate the effects of baby-led compared with scheduled (or mixed) breastfeeding for successful breastfeeding, for healthy newborns. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2016), CINAHL (1981 to 23 February 2016), EThOS, Index to Theses and ProQuest database and World Health Organization's 1998 evidence to support the 'Ten Steps' to successful breastfeeding (10 May 2016). SELECTION CRITERIA: We planned to include randomised and quasi-randomised trials with randomisation at both the individual and cluster level. Studies presented in abstract form would have been eligible for inclusion if sufficient data were available. Studies using a cross-over design would not have been eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion all potential studies we identified as a result of the search strategy. We would have resolved any disagreement through discussion or, if required, consulted a third review author, but this was not necessary. MAIN RESULTS: No studies were identified that were eligible for inclusion in this review. AUTHORS' CONCLUSIONS: This review demonstrates that there is no evidence from randomised controlled trials evaluating the effect of baby-led compared with scheduled (or mixed) breastfeeding for successful breastfeeding, for healthy newborns. It is recommended that no changes are made to current practice guidelines without undertaking robust research, to include many patterns of breastfeeding and not limited to baby-led and scheduled breastfeeding. Future exploratory research is needed on baby-led breastfeeding that takes the mother's perspective into consideration. PMID- 27673474 TI - Biomaterial-Based Approaches to Address Vein Graft and Hemodialysis Access Failures. AB - Veins used as grafts in heart bypass or as access points in hemodialysis exhibit high failure rates, thereby causing significant morbidity and mortality for patients. Interventional or revisional surgeries required to correct these failures have been met with limited success and exorbitant costs, particularly for the US Centers for Medicare & Medicaid Services. Vein stenosis or occlusion leading to failure is primarily the result of neointimal hyperplasia. Systemic therapies have achieved little long-term success, indicating the need for more localized, sustained, biomaterial-based solutions. Numerous studies have demonstrated the ability of external stents to reduce neointimal hyperplasia. However, successful results from animal models have failed to translate to the clinic thus far, and no external stent is currently approved for use in the US to prevent vein graft or hemodialysis access failures. This review discusses current progress in the field, design considerations, and future perspectives for biomaterial-based external stents. More comparative studies iteratively modulating biomaterial and biomaterial-drug approaches are critical in addressing mechanistic knowledge gaps associated with external stent application to the arteriovenous environment. Addressing these gaps will ultimately lead to more viable solutions that prevent vein graft and hemodialysis access failures. PMID- 27673480 TI - Molecularly Smooth Self-Assembled Monolayer for High-Mobility Organic Field Effect Transistors. AB - Despite the need for molecularly smooth self-assembled monolayers (SAMs) on silicon dioxide surfaces (the most common dielectric surface), current techniques are limited to nonideal silane grafting. Here, we show unique bioinspired zwitterionic molecules forming a molecularly smooth and uniformly thin SAM in "water" in <1 min on various dielectric surfaces, which enables a dip-coating process that is essential for organic electronics to become reality. This monomolecular layer leads to high mobility of organic field-effect transistors (OFETs) based on various organic semiconductors and source/drain electrodes. A combination of experimental and computational techniques confirms strong adsorption (Wad > 20 mJ m-2), uniform thickness (~0.5 or ~1 nm) and orientation (all catechol head groups facing the oxide surface) of the "monomolecular" layers. This robust (strong adsorption), rapid, and green SAM represents a promising advancement toward the next generation of nanofabrication compared to the current nonuniform and inconsistent polysiloxane-based SAM involving toxic chemicals, long processing time (>10 h), or heat (>80 degrees C). PMID- 27673479 TI - DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate. AB - BACKGROUND: Adolescence is a vulnerable period for the onset of major depressive disorder (MDD). While some studies have shown white matter alterations in adolescent MDD, there is still a gap in understanding how the brain is affected at a network level. METHODS: We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 57 adolescents with MDD and 41 well-matched healthy controls who completed self-reports of depression symptoms and stressful life events. Using atlas-based brain regions as network nodes and tractography streamline count or mean fractional anisotropy (FA) as edge weights, we examined weighted local and global network properties and performed Network-Based Statistic (NBS) analysis. RESULTS: While there were no significant group differences in the global network properties, the FA-weighted node strength of the right caudate was significantly lower in depressed adolescents and correlated positively with age across both groups. The NBS analysis revealed a cluster of lower FA-based connectivity in depressed subjects centered on the right caudate, including connections to frontal gyri, insula, and anterior cingulate. Within this cluster, the most robust difference between groups was the connection between the right caudate and middle frontal gyrus. This connection showed a significant diagnosis by stress interaction and a negative correlation with total stress in depressed adolescents. LIMITATIONS: Use of DTI-based tractography, one atlas-based parcellation, and FA values to characterize brain networks represent this study's limitations. CONCLUSIONS: Our results allowed us to suggest caudate centric models of dysfunctional processes underlying adolescent depression, which might guide future studies and help better understand and treat this disorder. PMID- 27673481 TI - Trilinear analysis of thin-layer chromatography retention of 35 model compounds chromatographed on nine adsorbents with 20 pure solvents. AB - The RF value dataset of 35 model compounds, chromatographed with 20 pure solvents as the mobile phase each on nine adsorbents: RP2, RP8, RP18, alumina, cellulose, CN, DIOL, NH2 , and silica, was subjected to trilinear analysis with parallel factor analysis. The two-factor optimal model explained 87% of total information in this complex dataset. The first obtained score (trend) represents two features: the presence of hydrogen bonding and heteroatoms of solute and the mean elution force of the solvent. The second trend represents molecule size, aromaticity, and number of carbons, interconnected with presence of chlorine in mobile phase. The correlation between the scores and molecular descriptors were checked to interpret these trends quantitatively. The scores of adsorbents were slightly intercorrelated, showing NH2 , alumina, and cellulose as outliers from main adsorbents cloud. The obtained results suggest that molecular size and aromaticity, connected with chlorine atoms in mobile phase, is the second source of retention variability. PMID- 27673482 TI - Development of Selective CBP/P300 Benzoxazepine Bromodomain Inhibitors. AB - CBP (CREB (cAMP responsive element binding protein) binding protein (CREBBP)) and P300 (adenovirus E1A-associated 300 kDa protein) are two closely related histone acetyltransferases (HATs) that play a key role in the regulation of gene transcription. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important for the targeting of CBP/P300 to chromatin and which offeres an opportunity for the development of protein-protein interaction inhibitors. Here we present the development of CBP/P300 bromodomain inhibitors with 2,3,4,5-tetrahydro-1,4-benzoxazepine backbone, an N-acetyl-lysine mimetic scaffold that led to the recent development of the chemical probe I-CBP112. We present comprehensive SAR of this inhibitor class as well as demonstration of cellular on target activity of the most potent and selective inhibitor TPOP146, which showed 134 nM affinity for CBP with excellent selectivity over other bromodomains. PMID- 27673484 TI - Facial Laxity Rating Scale Validation Study. AB - BACKGROUND: Age, weight change, clinical or surgical procedures, and distinctive characteristics, combine to be perceived as degrees of flaccidity. There is an absence of a validated scale to accurately assess the firmness-laxity spectrum of the face and neck with accepted classification and terminology. OBJECTIVE: To create a simplified assessment tool to measure the degree of laxity in the face and neck: the Facial Laxity Rating (FLR) scale. METHODS: The FLR scale evaluates 4 distinctive signs (eyelid folds, nasojugal folds, jowls, and neck profile) in 4 regions: upper face, middle face, lower face, and neck. This study incorporated a focused training component for 7 independent physician blinded photograph scorers. A total of 188 ratings were assessed. RESULTS: Combined weighted kappa inter-rater agreement was 0.77 (95% CI, 0.76-0.78) for 188 ratings. Mean inter rater agreement for laxity class was 0.78 (95% CI, 0.77-0.80). Agreement scoring relative to the truth standard was 92.53% (90.31-94.21), averaged for 7 investigators. CONCLUSION: This study effectively presents the validation of the FLR scale for both inter-rater and agreement relative to the truth standard, demonstrating that the FLR scale may be used as a reliable instrument for quantitative assessment of chronological or treatment related laxity of the face and neck. PMID- 27673483 TI - An 18-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Moderate Nasolabial Folds. AB - BACKGROUND: Hyaluronic acid (HA) filler injection is a popular nonsurgical aesthetic procedure. OBJECTIVE: To compare the effectiveness and safety of 2 hyaluronic acid fillers (HAEC and HARES) for treatment of moderate nasolabial folds (NLFs). MATERIALS AND METHODS: This was an evaluator- and subject-blinded split-face study. HAEC or HARES was randomly assigned to the left or right NLF at baseline. Retreatment was performed after 9 months; follow-up extended to 18 months after baseline (9 months after retreatment). Effectiveness assessments included the Wrinkle Severity Rating Scale (WSRS) and subject preference. Safety assessments included adverse events (AEs) and local tolerability symptoms recorded by subjects during 3 weeks after treatment. RESULTS: HAEC was noninferior to HARES measured as mean change from baseline in WSRS score at 6 months. Mean WSRS score change from baseline was similar between products up to 18 months. A majority of subjects (>70%) were still responders at 18 months (after retreatment at 9 months). The volume required at retreatment was approximately two-thirds of that at baseline. There was no difference in subject preference between products. Both fillers were well tolerated and associated with few treatment-related AEs. CONCLUSION: HAEC and HARES were effective and well tolerated for treatment of moderate NLFs. PMID- 27673485 TI - Umbilical Skin Endometriosis: Treatment, Reconstruction, and Differential Diagnosis. PMID- 27673486 TI - Large Surgical Defect of the Superior Ear. PMID- 27673487 TI - Second Intention Healing for Large Surgical Defects of the Foot. PMID- 27673488 TI - A Recalcitrant Keloid Successfully Treated With CO2 Laser and Indocyanine Green Photodynamic Therapy. PMID- 27673489 TI - Scalp Cyst Excision in an Unknown Previous Site of Neurosurgery: Issues in Patient Safety in Dermatologic Surgery. PMID- 27673490 TI - Thermodynamically Anchoring-Frustrated Surface to Trigger Bulk Discontinuous Orientational Transition. AB - Surface-specific liquid crystal (LC) nanostructures provide a unique platform for studying surface-wetting phenomena and also for technological applications. The most important studies on LC properties are related to bulk alignment, surface anchoring, and so on. Here, we study an LC system with a nematic liquid crystal (NLC) on a perfluoropolymer-coated substrate, in which a discontinuous bulk orientational transition has recently been found. Using free-energy analysis based on experimental results of the newly-conducted grazing-incidence X-ray diffraction (GI-XRD) measurements, we have confirmed a thermodynamic growth process of smectic liquid crystalline wetting nanosheets on the surface and successfully explained that a frustrated surface of planar and vertical anchoring states accompanied by an elastic energy cost kinetically triggers the bulk reorientation in the first-order manner. This interfacial bottom-up process may offer a general insight into how interfacial hierarchical molecular architectures alter the bulk properties of matter thermodynamically. PMID- 27673491 TI - Application of multiphysics models to efficient design of experiments of solute transport across articular cartilage. AB - Transport of solutes helps to regulate normal physiology and proper function of cartilage in diarthrodial joints. Multiple studies have shown the effects of characteristic parameters such as concentration of proteoglycans and collagens and the orientation of collagen fibrils on the diffusion process. However, not much quantitative information and accurate models are available to help understand how the characteristics of the fluid surrounding articular cartilage influence the diffusion process. In this study, we used a combination of micro computed tomography experiments and biphasic-solute finite element models to study the effects of three parameters of the overlying bath on the diffusion of neutral solutes across cartilage zones. Those parameters include bath size, degree of stirring of the bath, and the size and concentration of the stagnant layer that forms at the interface of cartilage and bath. Parametric studies determined the minimum of the finite bath size for which the diffusion behavior reduces to that of an infinite bath. Stirring of the bath proved to remarkably influence neutral solute transport across cartilage zones. The well-stirred condition was achieved only when the ratio of the diffusivity of bath to that of cartilage was greater than ~1000. While the thickness of the stagnant layer at the cartilage-bath interface did not significantly influence the diffusion behavior, increase in its concentration substantially elevated solute concentration in cartilage. Sufficient stirring attenuated the effects of the stagnant layer. Our findings could be used for efficient design of experimental protocols aimed at understanding the transport of molecules across articular cartilage. PMID- 27673493 TI - Ultrathin Colloidal Cesium Lead Halide Perovskite Nanowires. AB - Highly uniform single crystal ultrathin CsPbBr3 nanowires (NWs) with diameter of 2.2 +/- 0.2 nm and length up to several microns were successfully synthesized and purified using a catalyst-free colloidal synthesis method followed by a stepwise purification strategy. The NWs have bright photoluminescence (PL) with a photoluminescence quantum yield (PLQY) of about 30% after surface treatment. Large blue-shifted UV-vis absorption and PL spectra have been observed due to strong two-dimensional quantum confinement effects. A small angle X-ray scattering (SAXS) pattern shows the periodic packing of the ultrathin NWs along the radial direction, demonstrates the narrow radial distribution of the wires, and emphasizes the deep intercalation of the surfactants. Despite the extreme aspect ratios of the ultrathin NWs, their composition and the resulting optical properties can be readily tuned by an anion-exchange reaction with good morphology preservation. These bright ultrathin NWs may be used as a model system to study strong quantum confinement effects in a one-dimensional halide perovskite system. PMID- 27673492 TI - Extraction and processing of videocapsule data to detect and measure the presence of villous atrophy in celiac disease patients. AB - BACKGROUND: Videocapsule endoscopy is a relative new method to analyze the gastrointestinal tract for the presence of pathologic features. It is of relevance to detect villous atrophy in the small bowel, which is a defining symptom of celiac disease. METHOD: In this tutorial, methods to extract and process videocapsule endoscopy data are elucidated. The algorithms, computer code, and paradigms to analyze image series are described in detail. The topics covered include extraction of data, analysis of texture, eigenanalysis, spectral analysis, three-dimensional projection, and estimation of motility. The basic paradigms to implement these processes are provided. RESULTS: Examples of successful quantitative analysis implementations for selected untreated celiac disease patients with villous atrophy versus control patients with normal villi were illustrated. Based on the implementations, it was evident that celiac patients tended to have a rougher small intestinal texture as compared with control patients. From three-dimensional projection, celiac patients exhibited larger surface protrusions emanating from the small intestinal mucosa, which may represent clumps of atrophied villi. The periodicity of small intestinal contractions tends to be slower when villous atrophy is present, and the estimated degree of motility is reduced as compared with control image series. Basis image construction suggested that fissuring and mottling of the mucosal surface is predominant in untreated celiac patients, and mostly absent in controls. CONCLUSIONS: Implementation of computerized methods, as described in this tutorial, will likely be useful for the automated detection and measurement of villous atrophy, and to map its extent along the small intestine of celiac patients. PMID- 27673494 TI - Profiling of the Terpene Metabolome in Carrot Fruits of Wild ( Daucus carota L. ssp. carota) Accessions and Characterization of a Geraniol Synthase. AB - Fruits from wild carrot ( Daucus carota L. ssp. carota) have been used for medicinal purposes since ancient times. The oil of its seeds, with their abundant monoterpenes and sesquiterpenes, has drawn attention in recent years because of its potential pharmaceutical application. A combined chemical, biochemical, and molecular study was conducted to evaluate the differential accumulation of terpene volatiles in carrot fruits of wild accessions. This work reports a similarity-based cloning strategy identification and functional characterization of one carrot monoterpene terpene synthase, WtDcTPS1. Recombinant WtDcTPS1 protein produces mainly geraniol, the predominant monoterpene in carrot seeds of wild accession 23727. The results suggest a role for the WtDcTPS1 gene in the biosynthesis of carrot fruit aroma and flavor compounds. PMID- 27673495 TI - Ultrasensitive turn-on fluorescence detection of Cu2+ based on p dimethylaminobenzamide derivative and the application to cell imaging. AB - A new p-dimethylaminobenzamide derivative based compound BDIH has been synthesized. Cu2+ turned on the fluorescence of compound BDIH with a 1:2 binding stoichiometry. The fluorescent color of compound BDIH shows an evident change from colorless to bright blue upon the addition of Cu2+, which could be visibly detected by the naked eye under UV light at 365nm. More importantly, the detection limit was found to be 0.64nM which is far lower than the maximal allowed concentration of the WHO limit (31.5MUM) for drinking water. This selective "turn-on" fluorescence sensor was used to identify Cu2+ in living cells using confocal fluorescence microscopy, indicating that compound BDIH has a potential application for selective detection of Cu2+ in organism. PMID- 27673496 TI - Design, synthesis and DNA-binding study of some novel morpholine linked thiazolidinone derivatives. AB - The emergence of multiple drug resistance amongst bacterial strains resulted in many clinical drugs to be ineffective. Being vulnerable to bacterial infections any lack in the development of new antimicrobial drugs could pose a serious threat to public health. Here we report design and synthesis of a novel class of morpholine linked thiazolidinone hybrid molecules. The compounds were characterized by FT-IR, NMR and HRMS techniques. Susceptibility tests showed that most of the synthesized molecules were highly active against multiple bacterial strains. Compound 3f displayed MIC values which were better than the standard drug for most of the tested strains. DNA being a well defined target for many antimicrobial drugs was probed as possible target for these synthetic molecules. DNA-binding study of 3f with sm-DNA was probed through UV-vis absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. The studies revealed that compound 3f has strong affinity towards DNA and binds at the minor groove. The docking studies revealed that the compound 3f shows preferential binding towards A/T residues. PMID- 27673497 TI - Photophysical behavior and photodynamic therapy activity of conjugates of zinc monocarboxyphenoxy phthalocyanine with human serum albumin and chitosan. AB - Zinc monocarboxyphenoxy phthalocyanine (ZnMCPPc) was linked to human serum albumin (HSA) and chitosan via amide bond formation. The photophysical behavior and photodynamic therapy (PDT) activity (against human breast adenocarcinoma cell line (MCF-7 cells) of ZnMCPPc alone and its conjugates were investigated. The conjugates showed improved fluorescence, triplet and singlet oxygen quantum yields when compared to ZnMCPPc alone. The in vitro dark cytotoxicity and PDT studies were carried out at a dose of 3.6MUg/mL to 57.1MUg/mL. The in vitro dark cytotoxicity studies of ZnMCPPc showed cell viability <50% at 28.6MUg/mL and 57.1MUg/mL, while the conjugates showed > 50% in all their tested concentrations (3.6 to 57.1) MUg/mL. Thus, conjugation of ZnMCPPc to HSA and chitosan improves its dark cytotoxicity, an important criteria for molecules meant for photodynamic therapy. Complex 1 showed the most efficacious PDT activity with cell viability <50% at concentration range of (14.3 to 57.1) MUg/mL in comparison to the conjugates which only showed <50% cell viability at 28.6MUg/mL and 57.1MUg/mL for 1-HSA and 57.1MUg/mL for 1-Chitosan. PMID- 27673498 TI - Forster resonance energy transfer and excited state life time reduction of rhodamine 6G with NiO nanorods in PVP films. AB - In the present study, we report the preparation of NiO nanorods (NNR) and its Forster resonant energy transfer (FRET) behaviour with rhodamine 6G (R6G) in a Polyvinyl pyrrolidone (PVP) polymer matrix. The prepared nanocomposite polymer (NCP) films contain PVP and R6G whose concentrations are kept constant and different concentrations of NNR. Spectral overlap between the absorption and fluorescence spectrum of R6G and NNR shows the possibility of FRET phenomena to be occurring in the prepared NCP films. Steady state and time resolved fluorescence measurements are carried out at two excitation wavelengths (330 and 510nm) to study the energy transfer process between R6G and NNR in the PVP host. The obtained results show that the energy transfer is from R6G (serves as a donor) to NNR (functions as an acceptor). Calculated radiative efficiencies, donor-acceptor distances and average lifetime also confirm the energy transfer from R6G to NNR. PMID- 27673499 TI - Comparative structural and vibrational study of the four lowest energy conformers of serotonin. AB - A computational investigation of all possible lowest energy conformers of serotonin was carried out at the B3LYP/6-311++G** level. Out of the 14 possible lowest energy conformers, the first 4 conformers were investigated thoroughly for the optimized geometries, fundamental frequencies, the potential energy distributions, APT and natural charges, natural bond orbital (NBO) analysis, MEP, Contour map, total density array, HOMO, LUMO energies. The second third and fourth conformers are energetically at higher temperatures of 78, 94 and 312K respectively with respect to the first one. Bond angles and bond lengths do not show significant variations while the dihedral angles vary significantly in going from one conformer to the other. Some of the vibrational modes of the indole moiety are conformation dependent to some extent whereas most of the normal modes of vibration of amino-ethyl side chain vary significantly in going from one conformer to conformer. The MEP for the four conformers suggested that the sites of the maximum positive and negative ESP change on changing the conformation. The charges at some atomic sites also change significantly from conformer to conformer. PMID- 27673500 TI - Near infrared spectroscopy combined with chemometrics for growth stage classification of cannabis cultivated in a greenhouse from seized seeds. AB - Cannabis sativa L. (cannabis, Cannabaceae), popularly called marijuana, is one of the oldest plants known to man and it is the illicit drug most used worldwide. It also has been the subject of increasing discussions from the scientific and political points of view due to its medicinal properties. In recent years in Brazil, the form of cannabis drug trafficking has been changing and the Brazilian Federal Police has exponentially increased the number of seizures of cannabis seeds sent by the mail. This new form of trafficking encouraged the study of cannabis seeds seized germinated in a greenhouse through NIR spectroscopy combined with chemometrics. The plants were cultivated in a homemade greenhouse under controlled conditions. In three different growth periods (5.5weeks, 7.5weeks and 10weeks), they were harvested, dried, ground and directly analyzed. The iPCA was used to select the best NIR spectral range (4000-4375cm-1) in order to develop unsupervised and supervised methods. The PCA and HCA showed a good separation between the three groups of cannabis samples at different growth stages. The PLS-DA and SVM-DA classified the samples with good results in terms of sensitivity and specificity. The sensitivity and specificity for SVM-DA classification were equal to unity. This separation may be due to the correlation of cannabinoids and volatile compounds concentration during the growth of the cannabis plant. Therefore, the growth stage of cannabis can be predicted by NIR spectroscopy and chemometric tools in the early stages of indoor cannabis cultivation. PMID- 27673501 TI - DNA barcoding as a useful tool in the systematic study of wild bees of the tribe Augochlorini (Hymenoptera: Halictidae). AB - Special care is needed in the delimitation and identification of halictid bee species, which are renowned for being morphologically monotonous. Corynura Spinola and Halictillus Moure (Halictidae: Augochlorini) contain species that are key elements in southern South American ecosystems. These bees are very difficult to identify due to close morphological similarity among species and high sexual dimorphism. We analyzed 170 barcode-compliant COI sequences from 19 species. DNA barcodes were useful to confirm gender associations and to detect two new cryptic species. Interspecific distances were significantly higher than those reported for other bees. Maximum intraspecific divergence was less than 1% in 14 species. Barcode index numbers (BINs) were useful to identify putative species that need further study. More than one BIN was assigned to five species. The name Corynura patagonica (Cockerell) probably refers to two cryptic species. The results suggest that Corynura and Halictillus species can be identified using DNA barcodes. The sequences of the species included in this study can be used as a reference to assess the identification of unknown specimens. This study provides additional support for the use of DNA barcodes in bee taxonomy and the identification of specimens, which is particularly relevant in insects of ecological importance such as pollinators. PMID- 27673502 TI - Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development. AB - BACKGROUND: Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia. METHODS: We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement. RESULTS: We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology (p = 0.041) as well as interactions between NSS and ACC morphology (p = 0.005), between NSS and handedness (p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume (p = 0.005) on CC measured using the TMT-B score - the TMT-A score. LIMITATIONS: No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first episode psychosis. CONCLUSION: To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms. PMID- 27673503 TI - Cortical morphology as a shared neurobiological substrate of attention deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study. AB - BACKGROUND: Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimaging studies suggest that altered cortical development is related to ADHD. In a large population-based sample we investigated whether cortical morphology, as a potential neurobiological substrate, underlies the association between attention-deficit/hyperactivity symptoms and cognitive problems. METHODS: The sample consisted of school-aged children with data on attention-deficit/hyperactivity symptoms, cognitive functioning and structural imaging. First, we investigated the association between attention-deficit/ hyperactivity symptoms and different domains of cognition. Next, we identified cortical correlates of attention-deficit/hyperactivity symptoms and related cognitive domains. Finally, we studied the role of cortical thickness and gyrification in the behaviour-cognition associations. RESULTS: We included 776 children in our analyses. We found that attention-deficit/hyperactivity symptoms were associated specifically with problems in attention and executive functioning (EF; b = -0.041, 95% confidence interval [CI] -0.07 to -0.01, p = 0.004). Cortical thickness and gyrification were associated with both attention deficit/hyperactivity symptoms and EF in brain regions that have been previously implicated in ADHD. This partly explained the association between attention deficit/hyperactivity symptoms and EF (bindirect = -0.008, bias-corrected 95% CI 0.018 to -0.001). LIMITATIONS: The nature of our study did not allow us to draw inferences regarding temporal associations; longitudinal studies are needed for clarification. CONCLUSION: In a large, population-based sample of children, we identified a shared cortical morphology underlying attention deficit/hyperactivity symptoms and EF. PMID- 27673504 TI - RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay). AB - PURPOSE: In the framework of the 'Realizing the European Network of Biodosimetry' (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. MATERIALS AND METHODS: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. RESULTS: The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (<= 0.94 Gy). For higher dose points (>= 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. CONCLUSION: The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories. PMID- 27673505 TI - Ultra-low-dose Naloxone as an Adjuvant to Patient Controlled Analgesia (PCA) With Morphine for Postoperative Pain Relief Following Lumber Discectomy: A Double blind, Randomized, Placebo-controlled Trial. AB - BACKGROUND: Lumbar discectomy is one of the most commonly performed neurosurgical procedures. Many patients experience postoperative pain after lumbar discectomy. This study evaluated the effect of ultra-low-dose naloxone infusion on pain intensity after lumbar discectomy in individuals receiving patient-controlled analgesia (PCA) with morphine. MATERIALS AND METHODS: In a double-blind, randomized, controlled trial, a total of 80 patients scheduled for open discectomy was randomly assigned to receive naloxone (group N) or placebo (group P). After surgery, all patients were connected to a morphine PCA pump. Both groups received 500 mL of normal saline using a continuous infusion pump through a separate intravenous line for 24 hours. However, group N received a total dose of 0.25 MUg/kg/h naloxone, which was added to the normal saline infusion. All patients were asked to grade the intensity of their pain, severity of nausea, vomiting, and pruritus on a 0 to 10 visual analog scale before being discharged from the postanesthesia care unit and at 1, 6, 12, and 24 hours postoperatively. RESULTS: It was observed that both groups had a statistically significant (P<0.01) time trend difference for pain, nausea, and pruritus scores. A significant difference was found between the 2 groups in terms of intensity of pain, nausea, and pruritus, with the naloxone group experiencing a lower level in comparison with the placebo group. Moreover, the median (interquartile range) of morphine consumption after surgery for patients who received naloxone was 26 (24.25 to 28) mg, which is significantly (P<0.001) lower than for the placebo group, which had a median (interquartile range) of 34 (32 to 36) mg. CONCLUSIONS: It is concluded that infusion of ultra-low-dose naloxone (0.25 MUg/kg/h) along with morphine PCA can significantly reduce pain intensity, morphine consumption, and opioid-induced nausea and pruritus after lumbar discectomy. PMID- 27673506 TI - Sodium Bicarbonate for Control of ICP: A Systematic Review. AB - OBJECTIVE: Our goal was to perform a systematic review of the literature on the use of intravenous sodium bicarbonate for intracranial pressure (ICP) reduction in patients with neurologic illness. METHODS: Data sources: articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to April 2015), reference lists of relevant articles, and gray literature were searched. DATA EXTRACTION: 2 reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendation Assessment Development and Education methodology. RESULTS: Our search strategy produced a total 559 citations. Three original articles were included in the review. There were 2 prospective studies, 1 randomized control trial and 1 single arm, and 1 retrospective case report.Across all studies there were a total of 19 patients studied, with 31 episodes of elevated ICP being treated. Twenty-one of those episodes were treated with sodium bicarbonate infusion, with the remaining 10 treated with hypertonic saline in a control model. All elevated ICP episodes treated with sodium bicarbonate solution demonstrated a significant drop in ICP, without an elevation of serum partial pressure of carbon dioxide. No significant complications were described. CONCLUSIONS: There currently exists Oxford level 4, Grading of Recommendation Assessment Development and Education D evidence to support an ICP reduction effect with intravenous sodium bicarbonate in TBI. No comments on its impact in other neuropathologic states, or on patient outcomes, can be made at this time. PMID- 27673507 TI - A Survey of Incidence of Postoperative Visual Loss Associated With Spine Surgery Outside the United States. PMID- 27673508 TI - Effect of Bridging Local-Regional Therapy on Recurrence of Hepatocellular Carcinoma and Survival after Orthotopic Liver Transplantation. AB - Purpose To evaluate the influence of bridging local-regional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and overall survival after orthotopic liver transplantation and to identify factors that predict HCC recurrence after orthotopic liver transplantation. Materials and Methods The United Network for Organ Sharing database was used to identify patients with HCC who underwent liver transplantation between 2002 and 2013. Patients with complete explant data within the Milan criteria for whom a Model for End-Stage Liver Disease exception was approved were retrospectively analyzed. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazard models to assess independent prognostic factors for overall survival. Propensity-matched analysis for treatment groups was performed to minimize selection bias. Results The rate of tumor recurrence after liver transplantation was 11.5% (321 of 2794), which significantly decreased overall survival (P < .001). The bridging LRT group exhibited lower recurrence (59 of 686 [8.6%]; P = .02) and longer median overall survival (75.9 months; P < .001). Recurrence was higher in patients older than 60 years, serum alpha1-fetoprotein greater than 400 mg/L, bilobar distribution, multiple lesions, absent necrosis, microvascular invasion, and tumors beyond the Milan criteria (P < .05). Age, LRT status, serum alpha1-fetoprotein, and microvascular invasion were independent risk factors (P < .05). In the matched cohort, similar factors that predicted recurrence were observed (P < .05), whereas bridging LRT (P = .03) and serum alpha1-fetoprotein (P = .02) were independent risk factors for recurrence. Conclusion LRT significantly decreased tumor recurrence and lengthened overall survival. (c) RSNA, 2016. PMID- 27673509 TI - Peer Feedback, Learning, and Improvement: Answering the Call of the Institute of Medicine Report on Diagnostic Error. AB - In September 2015, the Institute of Medicine (IOM) published a report titled "Improving Diagnosis in Health Care," in which it was recommended that "health care organizations should adopt policies and practices that promote a nonpunitive culture that values open discussion and feedback on diagnostic performance." It may seem counterintuitive that a report addressing a highly technical skill such as medical diagnosis would be focused on organizational culture. The wisdom becomes clearer, however, when examined in the light of recent advances in the understanding of human error and individual and organizational performance. The current dominant model for radiologist performance improvement is scoring-based peer review, which reflects a traditional quality assurance approach, derived from manufacturing in the mid-1900s. Far from achieving the goals of the IOM, which are celebrating success, recognizing mistakes as an opportunity to learn, and fostering openness and trust, we have found that scoring-based peer review tends to drive radiologists inward, against each other, and against practice leaders. Modern approaches to quality improvement focus on using and enhancing interpersonal professional relationships to achieve and maintain high levels of individual and organizational performance. In this article, the authors review the recommendations set forth by the recent IOM report, discuss the science and theory that underlie several of those recommendations, and assess how well they fit with the current dominant approach to radiology peer review. The authors also offer an alternative approach to peer review: peer feedback, learning, and improvement (or more succinctly, "peer learning"), which they believe is better aligned with the principles promoted by the IOM. (c) RSNA, 2016. PMID- 27673510 TI - Clearance of Gadolinium from the Brain with No Pathologic Effect after Repeated Administration of Gadodiamide in Healthy Rats: An Analytical and Histologic Study. AB - Purpose To measure the levels of gadolinium present in the rat brain 1 and 20 weeks after dosing with contrast agent and to determine if there are any histopathologic sequelae. Materials and Methods The study was approved by the GE Global Research Center Institutional Animal Care and Use Committee. Absolute gadolinium levels were quantified in the blood and brains of rats 1 week after dosing and 20 weeks after dosing with up to 20 repeat doses of gadodiamide (cumulative dose, 12 mmol per kilogram of body weight) by using inductively coupled plasma-mass spectrometry. Treatment groups (n = 6 rats per group) included low-dosage and high-dosage gadodiamide and osmolality-matched saline controls. Brain sections were submitted (blinded) for standard toxicology assessment per Registry of Industrial Toxicology Animal data guidelines. Analysis of variance and Mann-Whitney U tests with post hoc correction were used to assess differences in absolute gadolinium levels and percentage of injected dose, respectively. Results Dose-dependent low levels of gadolinium were detected in the brain, a mean +/- standard deviation of 2.49 nmol per gram of brain tissue +/ 0.30 or 0.00019% of the injected dose 1 week after dosing. This diminished by approximately 50% (to 1.38 nmol per gram of brain tissue +/- 0.10 or 0.00011% of the injected dose) 20 weeks after dosing. As a percentage of injected dose, the levels of gadolinium measured were comparable between different doses, indicating that mechanisms of uptake and elimination were not saturated at the tested doses. There were no histopathologic findings associated with the levels of gadolinium measured. Conclusion Low levels of gadolinium are present in the brain after repeat dosing with gadodiamide, which is partially cleared over 20 weeks with no detectable neurotoxicity. PMID- 27673511 TI - Regulation of eosinophil development and survival. AB - PURPOSE OF REVIEW: Eosinophils are a subset of granulocytes generally associated with type 2 immune responses. They can contribute to protection against helminths but also mediate pro-inflammatory functions during allergic immune responses. Only recently, eosinophils were also found to exert many other functions such as regulation of glucose and fat metabolism, thermogenesis, survival of plasma cells, and antitumor activity. The mechanisms that control eosinophil development and survival are only partially understood. RECENT FINDINGS: Here we review new findings regarding the role of cell-extrinsic and cell-intrinsic factors for eosinophilopoiesis and eosinophil homeostasis. Several reports provide new insights in the regulation of eosinophil development by transcription factors, miRNAs and epigenetic modifications. Danger signals like lipopolysaccharide or alarmins can activate eosinophils but also prolong their lifespan. We further reflect on the observations that eosinophil development is tightly controlled by the unfolded protein stress response and formation of cytoplasmic granules. SUMMARY: Eosinophils emerge as important regulators of diverse biological processes. Their differentiation and survival is tightly regulated by factors that are still poorly understood. Newly identified pathways involved in eosinophilopoiesis and eosinophil homeostasis may lead to development of new therapeutic options for treatment of eosinophil-associated diseases. PMID- 27673512 TI - Short Link N Stimulates Intervertebral Disc Repair in a Novel Long-Term Organ Culture Model that Includes the Bony Vertebrae. AB - Link N (DHLSDNYTLDHDRAIH) is a peptide that occurs naturally in the intervertebral discs (IVDs) and cartilage as a result of proteolytic cleavage of Link protein. Several studies have identified Link N as a growth factor capable of stimulating matrix synthesis in these tissues. We have recently discovered that annulus fibrosus cells can release an enzyme (possibly cathepsin K) that can further cleave Link N resulting in an eight amino acid peptide, we called short Link N (sLink N). Separately, we recently developed and validated an organ culture model that has the vertebrae attached (vIVDs; IVD with intact vertebrae). The aims of this study were (i) to examine if sLink N has the potential to repair early degenerate discs and (ii) to determine if this new model can be used to test potential drugs for disc repair. To determine if sLink N was able to stimulate repair of the degenerate disc, vIVDs with trypsin-induced degeneration (DG) were used. After 4 weeks of culture, the proteoglycan content measured as glycosaminoglycans was stimulated by sLink N in the degenerated discs, and the staining of proteoglycan was observed throughout the tissue irrespective of its proximity to the cells. The quantity of extractable type II collagen and aggrecan was also increased when the degenerate discs were treated with sLink N. Taken together, the results suggest that sLink N can increase key disc matrix molecules, namely type II collagen and aggrecan. Thus sLink N is an attractive peptide for tissue engineering and regeneration of the disc due to its anabolic effects. Finally, we show the feasibility of using the long-term whole organ culture system with adjacent intact vertebrae for studying the DG and regeneration of the IVD. PMID- 27673513 TI - Postmastectomy Radiation Therapy and Two-Stage Implant-Based Breast Reconstruction: Is There a Better Time to Irradiate? AB - BACKGROUND: The ideal timing of postmastectomy radiation therapy (PMRT) in the setting of two-stage implant-based breast reconstruction remains unclear. In this cohort study, the authors sought to determine whether complication rates differed between patients who received PMRT following tissue expander placement (TE-XRT) and those who received PMRT after exchange for permanent implants (Implant-XRT) utilizing using prospective, multicenter data. METHODS: Eligible patients in the Mastectomy Reconstruction Outcomes Consortium study from 11 institutions across North America were included in the analysis. All patients had at least 6-month follow-up after their last intervention (i.e., implant exchange for TE-XRT patients, and radiation for Implant-XRT patients). Complications including seroma, hematoma, infection, wound dehiscence, capsular contracture, and implant loss were recorded. RESULTS: The authors identified a total of 150 patients who underwent immediate, two-stage implant-based breast reconstruction and received PMRT. Of these, there were TE-XRT 104 patients (69.3 percent) and 46 (30.7 percent) Implant-XRT patients. There were no differences in the incidence of any complications or complications leading to reconstructive failure between the two cohorts. After adjusting for patient characteristics and site effect, the timing of PMRT (i.e., TE-XRT versus Implant-XRT) was not a significant predictor in the development of any complication, a major complication, or reconstructive failure. CONCLUSION: In the setting of PMRT and two-stage implant-based reconstruction, patients who received PMRT after expander placement (TE-XRT) did not have a higher incidence or increased odds of developing complications than those who received PMRT after exchange for a permanent implant (Implant-XRT). CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27673514 TI - A Comparison of Psychological Response, Body Image, Sexuality, and Quality of Life between Immediate and Delayed Autologous Tissue Breast Reconstruction: A Prospective Long-Term Outcome Study. AB - BACKGROUND: This is the first study to use generic distress, cancer-specific, and procedure-specific measures to prospectively evaluate psychological responses, body image, sexuality, and health-related quality of life in immediate compared with delayed breast reconstruction. METHODS: Consecutive patients undergoing autologous immediate and delayed breast reconstruction (June of 2009 to December of 2010) completed the Hospital Anxiety and Depression Scale, Body Image Scale, Sexuality Scale, and BREAST-Q preoperatively and postoperatively (6, 12, and 18 months). Linear mixed-effects analyses between each outcome and time point were performed. RESULTS: One hundred six women underwent mastectomy with immediate (n = 30) and delayed breast reconstruction (n = 76). Before reconstruction, 26 percent of patients had abnormal anxiety scores and 9 percent had abnormal depression scores, with no significant differences between groups. Patients awaiting delayed breast reconstruction had significantly impaired prereconstruction body image (p = 0.01) and sexuality (p = 0.01) and worse satisfaction with breast (p < 0.01), psychological (p < 0.01), and sexual well being (p < 0.01). At 18 months after immediate and delayed breast reconstruction, there was significant improvement in anxiety, depression, body image, sexuality, and health-related quality of life. CONCLUSIONS: This single-center study shows that mastectomy with immediate breast reconstruction may protect breast cancer patients from a period of psychosocial distress, poor body image, and diminished sexual well-being compared with those waiting for delayed breast reconstruction. In patients who are oncologically eligible and strongly interested in breast reconstruction, efforts should be made to provide immediate breast reconstruction to decrease the interval of psychosocial distress, poor body image, and impaired sexuality. PMID- 27673515 TI - Revision Vaginoplasty: A Comparison of Surgical Outcomes of Laparoscopic Intestinal versus Perineal Full-Thickness Skin Graft Vaginoplasty. AB - BACKGROUND: Vaginal (re)construction can greatly improve the quality of life of indicated patients. If primary vaginoplasty fails, multiple surgical approaches exist for revision. The authors compared surgical results of laparoscopic intestinal versus full-thickness skin graft revision vaginoplasty. METHODS: A retrospective chart review of patients who underwent revision vaginoplasty at the authors' institution was conducted. Patient demographics, surgical characteristics, complications, hospitalization, reoperations, and neovaginal depth for both surgical techniques were recorded and compared. RESULTS: The authors studied a consecutive series of 50 transgender and three biological women who underwent revision vaginoplasty, of which 21 were laparoscopic intestinal and 32 were perineal full-thickness skin graft vaginoplasties, with a median clinical follow-up of 3.2 years (range, 0.5 to 19.7 years). Patient demographics did not differ significantly. There was no mortality. Two intraoperative rectal perforations (10 percent) occurred in the intestinal group versus six (19 percent) in the full-thickness skin graft group. Operative time was shorter for the full-thickness skin graft vaginoplasty group (131 +/- 35 minutes versus 191 +/- 45 minutes; p < 0.01). Hospitalization length did not differ significantly. Successful vaginal (re)construction was achieved in 19 intestinal (91 percent) and 26 full-thickness skin graft (81 percent) vaginoplasty procedures. A deeper neovagina was achieved with intestinal vaginoplasty (15.9 +/- 1.4 cm versus 12.5 +/- 2.8 cm; p < 0.01). CONCLUSIONS: Both laparoscopic intestinal and full thickness skin graft vaginoplasty can be used as secondary vaginal reconstruction. Intraoperative and postoperative complications do not differ significantly, but rectal perforation was more prevalent in the full-thickness skin graft vaginoplasty group. Although the operative time of laparoscopic intestinal vaginoplasty is longer, adequate neovaginal depth was more frequently achieved than in secondary perineal full-thickness skin graft vaginoplasty. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27673516 TI - Advancements and Refinement in Facial Neuromodulators. AB - The use of neuromodulators has increased by approximately 748 percent from 2000 to 2014 and has become an integral adjunct for facial rejuvenation. Knowledge of facial anatomy, accurate facial analysis, and familiarity with neurotoxin characteristics will minimize complications and optimize results. Current U.S. Food and Drug Administration-approved neurotoxins in the United States include onabotulinumtoxin A (Botox), abobotulinumtoxin A (Dysport), and incobotulinumtoxin A (Xeomin). The dosage and effect of these products are not interchangeable, so practitioners should master the utility and response of one product before trying the other products. All products have equivalent success in appropriately trained hands; the senior author (R.J.R.) favors no particular neurotoxin. This article provides a stepwise approach to treat dynamic facial rhytides with neuromodulators, including indications, facial analysis, preparation and injection technique, post-procedure care, and complications. PMID- 27673517 TI - Flow-Induced Axial Vascularization: The Arteriovenous Loop in Angiogenesis and Tissue Engineering. AB - Fabrication of a viable vascular network providing oxygen supply is identified as one crucial limiting factor to generate more complex three-dimensional constructs. The arteriovenous loop model provides initial blood supply and has a high angioinductive potency, making it suitable for vascularization of larger, tissue-engineered constructs. Also because of its angiogenic capabilities the arteriovenous loop is recently also used as a model to evaluate angiogenesis in vivo. This review summarizes the history of the arteriovenous loop model in research and its technical and surgical aspects. Through modifications of the isolation chamber and its containing matrices, tissue generation can be enhanced. In addition, matrices can be used as release systems for local application of growth factors, such as vascular endothelial growth factor and basic fibroblast growth factor, to affect vascular network formation. A special focus in this review is set on the assessment of angiogenesis in the arteriovenous loop model. This model provides good conditions for assessment of angiogenesis with the initial cell-free environment of the isolation chamber, which is vascularized by the arteriovenous loop. Because of the angiogenic capabilities of the arteriovenous loop model, different attempts were performed to create functional tissue in the isolation chamber for potential clinical application. Arteriovenous loops in combination with autologous bone marrow aspirate were already used to reconstruct large bone defects in humans. PMID- 27673518 TI - The Effect of Smoking on Necrosis Rate in Digital Replantation and Revascularization with Prostaglandin E1 Therapy: A Retrospective Study. AB - BACKGROUND: Most microsurgeons believe that smoking and severity of injury adversely affect the outcome of digital replantation surgery. As countermeasures, several pharmacologic agents have been used for the perioperative period. The purpose of this retrospective study was to examine whether the rate of necrosis is appreciably different across smokers versus nonsmokers with prostaglandin E1 therapy. METHODS: The authors' study subjects included 144 patients (184 digits) who underwent replantation or revascularization between August of 2013 and August of 2015.The primary outcome was the incidence of total necrosis after replantation surgery, and the secondary outcomes were the rate of overall necrosis, proportion of total necrosis to overall necrosis, and total success. Intravenous administration of prostaglandin E1 was performed at the rate of 120 MUg/day for 7 days after surgery in all patients. These outcomes of each injury type were compared between smoking and nonsmoking groups. RESULTS: Among the 184 injured digits, the incidence of total necrosis in smokers (23 percent) was higher than that in nonsmokers (17 percent), although no significant difference was shown (p = 0.36). The adjusted odds ratio was 1.17 (95 percent CI, 0.51 to 2.69). Similarly, there was no significant difference in the secondary outcomes between the two groups. CONCLUSION: The authors' retrospective study found no significant difference in the formation or extent of necrosis after replantation or revascularization between smoking and nonsmoking groups when all patients were treated with prostaglandin E1. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II. PMID- 27673519 TI - Crowdsourcing as a Novel Method to Evaluate Aesthetic Outcomes of Treatment for Unilateral Cleft Lip. AB - BACKGROUND: Lack of convenient and reliable methods to grade aesthetic outcomes limits the ability to study results and optimize treatment of unilateral cleft lip. Crowdsourcing methods solicit contributions from a large group to achieve a greater task. The authors hypothesized that crowdsourcing could be used to reliably grade aesthetic outcomes of unilateral cleft lip. METHODS: Fifty deidentified photographs of 8- to 10-year-old subjects (46 with unilateral cleft lip and four controls) were assembled. Outcomes were assessed using multiple pairwise comparisons that produced a rank order (Elo rank) of nasal appearance and, on a separate survey, by Asher-McDade ratings. Both surveys were repeated to assess reliability. A group of expert surgeons repeated the same tasks on a smaller subset of photographs. RESULTS: The authors obtained 2500 and 1900 anonymous, layperson evaluations by means of crowdsourcing on each Elo rank and Asher-McDade survey, respectively. Elo rank and Asher-McDade scores were highly reproducible (correlation coefficients, 0.87 and 0.98), and crowd evaluations agreed with those by expert surgeons (0.980 and 0.96 for Elo rank and Asher McDade score, respectively). Crowdsourcing surveys were completed within 9 hours, whereas the expert surgeons required 3 months. On further analysis of their cleft subject sample set, the authors found that greater initial cleft severity was associated with worse aesthetic outcome. CONCLUSIONS: Outcomes assessed by crowds were reliable and correlated well with expert assessments. Crowdsourcing allows acquisition of massive numbers of layperson assessments on an unprecedented scale, and is a convenient, rapid, and reliable means of assessing aesthetic outcome of treatment for unilateral cleft lip. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV. PMID- 27673520 TI - Discussion: Crowdsourcing as a Novel Method to Evaluate Aesthetic Outcomes of Treatment for Unilateral Cleft Lip. PMID- 27673521 TI - Obstructive Sleep Apnea in Adults: The Role of Upper Airway and Facial Skeletal Surgery. AB - Obstructive sleep apnea represents a large burden of disease to the general population and may compromise patient quality of life; workplace and automotive safety; and metabolic, cardiovascular, and neurocognitive health. The disease is characterized by repetitive cycles of upper airway collapse resulting from a lack of pharyngeal airway structural support and loss of muscle tone among upper airway dilators. Polysomnography serves as the gold standard for diagnosis of obstructive sleep apnea and the apnea-hypopnea index is the most commonly used metric for quantifying disease severity. Conservative treatments include lifestyle modification, continuous positive airway pressure treatment, and dental appliance therapy. Surgical treatment options include pharyngeal and facial skeletal surgery. Maxillomandibular advancement has been shown to be the most effective surgical approach for multilevel expansion of the upper airway and may significantly reduce an obstructive sleep apnea patient's apnea-hypopnea index. Patient age, obesity, and the degree of maxillary advancement may be key factors contributing to treatment success. PMID- 27673522 TI - Proximal-to-Distally Elevated Superficial Circumflex Iliac Artery Perforator Flap Enabling Hybrid Reconstruction. AB - BACKGROUND: Most authors elevate the superficial circumflex iliac artery perforator flap from the lateral edge of the skin paddle, and begin by dissecting a perforator perfusing the skin paddle. In this article, the authors introduce a modified technique for elevation of a superficial circumflex iliac artery perforator flap, beginning with identification of the pedicle arteries, allowing inclusion of a variety of anatomical structures. METHODS: From August of 2012 to August of 2015, 27 patients with soft- and bony-tissue defects underwent reconstruction using proximal-to-distally elevated superficial circumflex iliac artery perforator flaps. There were 18 male and nine female patients, with an average age was 54.3 years. RESULTS: The average size and pedicle length of the flap was 59 cm and 6 cm, respectively. Chimeric fabrication consisted of vascularized iliac bone in four patients, the sartorius muscle in three patients, vascularized lymph node in two patients, vascularized deep fascia in one patient, and the intercostal nerve in one patient. The superficial branch of the superficial circumflex iliac artery was used as the only pedicle in 20 cases, the deep branch of the superficial circumflex iliac artery was used as the only pedicle in three cases, and both branches were used as the pedicle in four cases. Flaps survived completely in all but three cases. In the cases with integrated nerves or fascia, satisfactory functional recovery was observed. CONCLUSION: With its minimal donor-site morbidity and a wide variety of anatomical structures that can be procured with the skin paddle, the proximal-to-distally elevated superficial circumflex iliac artery perforator flap may be useful for reconstruction of defects of small to moderate size. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27673523 TI - Making the End as Good as the Beginning: Financial Planning and Retirement for Women Plastic Surgeons. AB - Financial planning is critically important to ensure financial security both during a plastic surgical career and in retirement. Unfortunately, plastic surgery training includes very little in the way of financial planning. The information that is available in the literature is mostly geared toward men. Women, with longer lifespans and more family care responsibilities, have unique needs when it comes to financial planning. Adequate attention must also be paid to life after retirement. A plastic surgical career can be all-encompassing, and thus women need to carefully plan volunteer activities, new hobbies, and even a second career to make their retirement years fulfilling and enjoyable. Key points regarding financial planning during the various phases of a woman plastic surgeon's career are discussed. Options for retirement are presented. PMID- 27673524 TI - Discussion: Making the End as Good as the Beginning: Financial Planning and Retirement for Women Plastic Surgeons. PMID- 27673527 TI - Impact of Prior Unilateral Chest Wall Radiotherapy on Outcomes in Bilateral Breast Reconstruction. AB - BACKGROUND: The purpose of this study was to evaluate the impact of prior unilateral chest wall radiotherapy on reconstructive outcomes among patients undergoing bilateral immediate breast reconstruction. METHODS: A retrospective evaluation of patients with a history of unilateral chest wall radiotherapy was performed. In each patient, the previously irradiated and reconstructed breast was compared to the contralateral nonirradiated side, which served as an internal control. Descriptive and bivariate statistics were computed. Multiple regression statistics were computed to identify adjusted associations between chest wall radiotherapy and complications. RESULTS: Seventy patients were included in the study. The mean follow-up period was 51.8 months (range, 10 to 113 months). Thirty-eight patients underwent implant-based breast reconstruction; 32 patients underwent abdominal autologous flap reconstruction. Previously irradiated breast had a significantly higher rate of overall complications (51 percent versus 27 percent; p < 0.0001), infection (13 percent versus 6 percent; p = 0.026), and major skin necrosis (9 percent versus 3 percent; p = 0.046). After adjusting for age, body mass index, reconstruction method, and medical comorbidities, prior chest wall radiotherapy was a significant risk factor for breast-related complications (OR, 2.98; p < 0.0001), infection (OR, 2.59; p = 0.027), and major skin necrosis (OR, 3.47; p = 0.0266). There were no differences between implant based and autologous reconstructions with regard to complications (p = 0.76). CONCLUSION: Prior chest wall radiotherapy is associated with a 3-fold increased risk of postoperative complications following immediate breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 27673528 TI - Discussion: Impact of Prior Unilateral Chest Wall Radiotherapy on Outcomes in Bilateral Breast Reconstruction. PMID- 27673529 TI - Predictors of Complications and Comparison of Outcomes Using SurgiMend Fetal Bovine and AlloDerm Human Cadaveric Acellular Dermal Matrices in Implant-Based Breast Reconstruction. AB - BACKGROUND: Implant-based breast reconstruction with an acellular dermal matrix is one of the most common procedures performed by plastic surgeons. Although numerous matrices are available, there is little literature comparing them. This study compares the rates of complications between two commonly used products: AlloDerm (human cadaveric) and SurgiMend (fetal bovine) acellular dermal matrices. METHODS: A retrospective review of a single center's 6-year experience was performed for consecutive, immediate breast reconstructions with acellular dermal matrix from 2009 to 2014. The authors compared demographics and surgical characteristics between patients receiving AlloDerm versus SurgiMend. Multivariate logistic regression was used to determine any association between type of matrix and surgical complications and to identify other clinical predictors for complications. RESULTS: A total of 640 patients underwent 952 reconstructions using AlloDerm [578 breasts (61 percent)] or SurgiMend [374 breasts (39 percent)]. The average follow-up was 587 days. Multivariate analysis revealed that type of matrix was not an independent risk factor for the development of complications. However, smoking, age, radiotherapy, and initial tissue expander fill volume were associated with increased risk of postoperative complications. CONCLUSIONS: Both AlloDerm and SurgiMend acellular dermal matrices demonstrate similar rates of major complications when used in immediate implant based breast reconstruction. In contrast, preoperative radiation therapy, smoking, increasing age, and initial tissue expander fill volume are independent risk factors for postoperative complications. Reconstructive surgeons should take these findings into consideration when performing implant-based breast reconstruction with a dermal matrix. PMID- 27673530 TI - Reducing Decisional Conflict and Enhancing Satisfaction with Information among Women Considering Breast Reconstruction following Mastectomy: Results from the BRECONDA Randomized Controlled Trial. AB - BACKGROUND: Deciding whether or not to have breast reconstruction following breast cancer diagnosis is a complex decision process. This randomized controlled trial assessed the impact of an online decision aid [Breast RECONstruction Decision Aid (BRECONDA)] on breast reconstruction decision-making. METHODS: Women (n = 222) diagnosed with breast cancer or ductal carcinoma in situ, and eligible for reconstruction following mastectomy, completed an online baseline questionnaire. They were then assigned randomly to receive either standard online information about breast reconstruction (control) or standard information plus access to BRECONDA (intervention). Participants then completed questionnaires at 1 and 6 months after randomization. The primary outcome was participants' decisional conflict 1 month after exposure to the intervention. Secondary outcomes included decisional conflict at 6 months, satisfaction with information at 1 and 6 months, and 6-month decisional regret. RESULTS: Linear mixed-model analyses revealed that 1-month decisional conflict was significantly lower in the intervention group (27.18) compared with the control group (35.5). This difference was also sustained at the 6-month follow-up. Intervention participants reported greater satisfaction with information at 1- and 6-month follow-up, and there was a nonsignificant trend for lower decisional regret in the intervention group at 6-month follow-up. Intervention participants' ratings for BRECONDA demonstrated high user acceptability and overall satisfaction. CONCLUSIONS: Women who accessed BRECONDA benefited by experiencing significantly less decisional conflict and being more satisfied with information regarding the reconstruction decisional process than women receiving standard care alone. These findings support the efficacy of BRECONDA in helping women to arrive at their breast reconstruction decision. PMID- 27673531 TI - "No-Touch" Technique for Lip Enhancement. AB - BACKGROUND: The purpose of this study was to examine the anatomical principles of lip structure as they relate to individualized lip enhancement procedures and to describe a technique that does not violate lip mucosa during injection. METHODS: A retrospective analysis of patients undergoing lip enhancement procedures between 2001 and 2014 was performed. Preprocedural and postprocedural photographs were analyzed for lip subunit changes. A stepwise treatment algorithm targeting specific anatomical subunits of lip is described. RESULTS: Four hundred ten patients were treated with a "no-touch" technique for lip enhancement. Lip profile is determined by the position of the white roll. The white roll is accessed by a 30-gauge needle at a point 5 mm lateral to the oral commissure and at the base of the philtral columns. Lip projection is established by vermilion formation contributing to the arc of the Cupid's bow. To improve projection, the labial commissure is entered with a 25-gauge cannula and tunneled into the submucosal space between the white and red rolls. Lip augmentation is a direct reflection of the prominence of the red line and can be approached in a perpendicular fashion with a needle or cannula descending to the level of the wet dry junction. CONCLUSIONS: Accurate assessment of the white and red rolls, arc of Cupid's bow, philtrum, and gingival show can guide the injector on the proper enhancement that individual patients require. The no-touch technique minimizes mucosal trauma. Tailoring treatment toward lip profile, projection, and/or augmentation can yield predictable and reproducible outcomes in this commonly performed cosmetic procedure. PMID- 27673532 TI - Primary Total Laparoscopic Sigmoid Vaginoplasty in Transgender Women with Penoscrotal Hypoplasia: A Prospective Cohort Study of Surgical Outcomes and Follow-Up of 42 Patients. AB - BACKGROUND: In young transgender women previously treated with puberty suppressing hormones, penoscrotal hypoplasia can make penoscrotal inversion vaginoplasty unfeasible. The aim of this study was to prospectively assess surgical outcomes and follow-up of total laparoscopic sigmoid vaginoplasty as primary reconstruction in a cohort of transgender women with penoscrotal hypoplasia. METHODS: Baseline demographics, surgical characteristics, and intraoperative and postoperative complications of all performed total laparoscopic sigmoid vaginoplasty procedures were prospectively recorded. RESULTS: From November of 2007 to July of 2015, 42 transgender women underwent total laparoscopic sigmoid vaginoplasty as primary vaginal reconstruction. The mean age at the time of surgery was 21.1 +/- 4.7 years. Mean follow-up time was 3.2 +/- 2.1 years. The mean operative duration was 210 +/- 44 minutes. There were no conversions to laparotomy. One rectal perforation was recognized during surgery and immediately oversewn without long-term consequences. The mean length of hospitalization was 5.7 +/- 1.1 days. One patient died as a result of an extended-spectrum beta-lactamase-positive necrotizing fasciitis leading to septic shock, with multiorgan failure. Direct postoperative complications that needed laparoscopic reoperation occurred in three cases (7.1 percent). In seven cases (17.1 percent), long-term complications needed a secondary correction. After 1 year, all patients had a functional neovagina with a mean depth of 16.3 +/- 1.5 cm. CONCLUSIONS: Total laparoscopic sigmoid vaginoplasty seems to have a similar complication rate as other types of elective laparoscopic colorectal surgery. Primary total laparoscopic sigmoid vaginoplasty is a feasible gender-confirming surgical technique with good functional outcomes for transgender women with penoscrotal hypoplasia. CLINICAL QUESTIO/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27673533 TI - How Should Results of Nonsurgical Subcutaneous Fat Removal Be Assessed? Accuracy of B-Mode Ultrasound. AB - BACKGROUND: Nonsurgical fat reduction has become extremely popular among patients; however, a reliable method of measuring its efficacy has not been established. METHODS: Ultrasound measurement of human female abdominal subcutaneous fat thickness was carried out on five volunteers. Forty-seven measurements were performed using a GE Venue 40 diagnostic ultrasound device with a 12-MHz transducer. Transducer pressure measurements were recorded simultaneously according to the protocol described by Toomey et al.. RESULTS: Reproducible measurements of abdomen subcutaneous fat could be consistently achieved with a margin of error (95 percent CI) of +/-0.558 mm. CONCLUSIONS: Using a protocol with a transducer pressure less than 1 N (Toomey protocol) allows accurate and reliable measurement of subcutaneous fat. The authors further conclude that such a protocol is practically reproducible in the clinical setting and should be the standard for evaluating the results of nonsurgical fat removal, particularly in the abdomen. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV. PMID- 27673534 TI - Flexor Tendon Sheath Engineering Using Decellularized Porcine Pericardium. AB - BACKGROUND: The flexor tendon sheath is an ideal target for tissue engineering because it is difficult to reconstruct by conventional surgical methods. The authors hypothesized that decellularized porcine pericardium can be used as a scaffold for engineering a biologically active tendon sheath. METHODS: The authors' protocol removed cellular material from the pericardium and preserved the structural architecture in addition to the collagen and glycosaminoglycan content. The scaffold was successfully reseeded with human sheath synoviocytes and human adipose-derived stem cells. Cells were evaluated for 8 weeks after reseeding. RESULTS: The reseeded construct demonstrated continuous production of hyaluronic acid, the main component of synovial fluid. After being seeded on the membrane, adipose-derived stem cells demonstrated down-regulation of collagen I and III and up-regulation of hyaluronan synthase 2. CONCLUSION: The results indicate that decellularized porcine pericardium may be a potential scaffold for engineering a biologically active human tendon sheath. PMID- 27673535 TI - Regulation of ADSC Osteoinductive Potential Using Notch Pathway Inhibition and Gene Rescue: A Potential On/Off Switch for Clinical Applications in Bone Formation and Reconstructive Efforts. AB - BACKGROUND: Although there has been tremendous research in the ability of mesenchymal-derived adipose derived stem cells (ADSCs) to form bone, less is known regarding the molecular mechanisms that regulate the osteogenic potential of ADSCs. Notch, which consists of a key family of regulatory ligands involved in bone formation, is expressed in the bone marrow-derived mesenchymal stem cell niche and is critical for proliferation, migration, and ultimately osseous differentiation. The authors investigate how Notch impacts ADSC proliferation and osteogenic differentiation to determine a translatable application of these cells in bone regeneration. METHODS: Enriched ADSC populations were isolated from tissue and examined for their ability to respond to Notch pathway signaling events. Proliferation, viability, extracellular matrix deposition, and osteoinduction were assessed following Notch activation and inhibition. Notch pathway rescue was conducted using a lentiviral vector encoding a downstream Notch-1 intracellular domain (NICD). RESULTS: Proliferation, osteogenic induction, and the ability to form bone elements were reduced following Notch inhibition (p < 0.05). However, ADSCs, while in the presence of the Notch inhibition, were able to be rescued following lentiviral transduction with NICD, restoring osteogenic potential at both the molecular and cellular functional levels (p < 0.05). CONCLUSIONS: These data suggest a potential translatable "on/off switch," using endogenous Notch signaling to regulate the proliferation, differentiation, and osteogenic potential of ADSCs. Although Notch inhibition reduced ADSC proliferation and down-regulated osteoinduction, targeted gene therapy and the delivery of the downstream NICD peptide restored bone formation, suggesting pragmatic clinical utility of ADSCs for bone regeneration. PMID- 27673536 TI - Hemodynamic Study of Three Patterns of Flaps on Rats with a Novel Panoramic Photographing Technique Involved. AB - BACKGROUND: No study heretofore has been conducted to investigate the hemodynamic characteristics of the perforator, perforator-plus, and random flaps on an animal model. METHODS: Thirty Sprague-Dawley rats were equally divided into three groups: the perforator group, the perforator-plus group, and the random group. Laser Doppler flowmetry was adopted for measurement of blood perfusion of the flaps at six time points. Another nine rats were equally divided into three groups and underwent the corresponding surgery. On day 7, the flaps were photographed for calculation of the necrosis rate. The vascular network of flaps in each group was photographed immediately postoperatively and at days 3 and 7 after surgery with a special technique first proposed by us. RESULTS: No significant difference in flap necrosis could be detected in the perforator and perforator-plus flaps. Other than on day 1, when perfusion of the perforator was significantly stronger than that of the perforator-plus flap, there was no significant difference between the perforator and perforator-plus flaps. The three perforasomes in the perforator and perforator-plus flaps could all survive because of considerable dilation of vessels. On day 7, the vascular network between the iliolumbar perforator and the sacrococcygeal perforators underwent tremendous enlargement in diameter in the random flap group. CONCLUSIONS: The perforator flap and the perforator-plus flap are equal in blood perfusion. The survival of the random flap depends on the dilation of the vascular network between the pedicle and the nearest potential perforator. PMID- 27673537 TI - Biomechanical Analysis of Barbed Suture in Flexor Tendon Repair versus Conventional Method: Systematic Review and Meta-Analysis. AB - BACKGROUND: The barbed suture technique uses newly developed materials for flexor tendon repair. In this study, the authors examine the effectiveness of using barbed sutures in flexor tendon repair compared with conventional methods. METHODS: A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Barbed suture and conventional suture methods were extracted as predictor variables, and maximum force, gap formation force, and cross-sectional area were extracted as outcome variables. Subgroup analyses were performed according to the source of suture materials and the number of strands. The Newcastle-Ottawa Scale was used to assess the quality of studies. Publication bias was evaluated using funnel plots. RESULTS: The search strategy identified 86 publications. After screening, 12 articles were selected for review. Barbed sutures are comparable in effectiveness to conventional methods in terms of maximum force, gap formation force, and cross-sectional area. In the subgroup analysis, barbed sutures also have comparable effects to conventional methods in terms of maximum force and gap formation force. CONCLUSIONS: The authors' meta-analysis found that the use of barbed sutures in flexor tendon repair was competitive compared to conventional methods in terms of maximum force and gap formation force. Long-term in vivo studies are needed to confirm these findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 27673538 TI - The Feasibility and Validity of PROMIS: A Novel Measure of Quality of Life among Children with Cleft Lip and Palate. AB - BACKGROUND: Health-related quality of life is inconsistently captured among children with cleft lip and palate. The Patient-Reported Outcomes Measurement Information System (PROMIS) captures health-related quality of life, with the added benefit of comparability across clinical conditions. In this study, the authors define the validity and feasibility of PROMIS among children with clefts. METHODS: Children with cleft lip and palate who were at least 5 years old and able to complete instruments independently were eligible for inclusion (n = 93). Children completed PROMIS anxiety, depression, and peer relationship item banks as short forms or computerized adaptive tests. Participants also completed the Pediatric Quality of Life Inventory. Construct validity was measured by Spearman correlations between PROMIS and the Pediatric Quality of Life Inventory controlling for race, sex, age, and income. Feasibility was measured using instrument completion time, reading level, and floor/ceiling effects. RESULTS: PROMIS computerized adaptive tests (peer relationship, r = 0.49; depression, r = 0.56; and anxiety, r = -0.36) and short forms (peer relationship, r = 0.65; depression, r = -0.54; and anxiety, r = -0.56) demonstrated moderate correlation with the Pediatric Quality of Life Inventory. Computerized adaptive tests had fewer floor (0 percent versus 0 percent) and ceiling (8.6 to 19.3 percent versus 21.8 to 41.9 percent) effects than short forms, and demonstrated better readability. Computerized adaptive tests required more time than short forms (peer relationship, 0.84 +/- 0.67 versus 1.3 +/- 0.92; depression, 0.52 +/- 0.38 versus 1.1 +/- 0.73; and anxiety, 0.53 +/- 0.23 versus 1.1 +/- 0.62; p = 0.001), as each computerized adaptive test included on average four more questions. CONCLUSIONS: PROMIS correlates well with the Pediatric Quality of Life Inventory and demonstrates similar accuracy, with better readability and efficiency. Use of PROMIS will improve our ability to compare children with cleft lip and palate to diverse populations and clinical conditions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II. PMID- 27673539 TI - An Evidence-Based Approach to Nonsynostotic Plagiocephaly. AB - This article provides an evidence-based review of the literature concerning the cause, diagnosis, manifestations, and treatment of nonsynostotic plagiocephaly, with a particular focus on recently published studies of helmet therapy. It is designed to serve as an overview of this very common abnormality and a stimulus for discussion about management paradigms and future research priorities. PMID- 27673540 TI - A Retrospective Analysis of Secondary Revisions after Face Transplantation: Assessment of Outcomes, Safety, and Feasibility. AB - BACKGROUND: Face transplantation has emerged as a viable option for certain patients in the treatment of devastating facial injuries. However, as with autologous free tissue transfer, the need for secondary revisions in face transplantation also exists. The authors' group has quantified the number of revision operations in their cohort and has assessed the rationale, safety, and outcomes of posttransplantation revisions. METHODS: A retrospective analysis of prospectively collected data of the authors' seven face transplants was performed from April of 2009 to July of 2015. The patients' medical records, preoperative facial defects, and all operative reports (index and secondary revisions) were critically reviewed. RESULTS: The average number of revision procedures was 2.6 per patient (range, zero to five procedures). The median time interval from face transplantation to revision surgery was 5 months (range, 1 to 10 months). Most interventions consisted of debulking of the allograft, superficial musculoaponeurotic system plication and suspension, and local tissue rearrangement. There were no major infections, allograft skin flap loss, or necrosis. One patient suffered a postoperative complication after autologous fat grafting in the form of acute rejection that resolved with pulse steroids. CONCLUSIONS: Secondary revisions after face transplantation are necessary components of care, as they are after most conventional free tissue transfers. Secondary revisions after face transplantation at the authors' institution have addressed both aesthetic and functional reconstructive needs, and these procedures have proven to be safe in the context of maintenance immunosuppression. Patient and procedure selection along with timing are essential to ensure patient safety, optimal function, and aesthetic outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 27673541 TI - A New Approach for Reconstruction of Diabetic Foot Wounds Using the Angiosome and Supermicrosurgery Concept. AB - BACKGROUND: Major vessels in the diabetic foot are often calcified and inadequate for use as recipient vessels. Thus, a supermicrosurgery technique using small branches or perforators from other collateral vessels with an adequate pulse may be an alternative method. This study evaluated outcome using the supermicrosurgery concept and the risk factors involved. METHODS: Ninety-five cases of diabetic foot reconstruction were reviewed; the average patient age was 57 years; average follow-up was 43.5 months. Debridement was performed according to the angiosome concept, and reconstruction was performed with perforator flaps using the supermicrosurgery approach. Correlation between total flap loss and 16 preoperative risk factors (age, sex, diabetes mellitus type, smoking, immunosuppression, flap size, hemoglobin A1c, ankle-brachial index, preoperative transcutaneous partial pressure of oxygen, C-reactive protein, computed tomographic angiography, amputation history, peripheral artery disease, American Society of Anesthesiologists physical status, osteomyelitis, and chronic renal failure) were analyzed. RESULTS: Of 95 cases, nine cases of total loss and 12 of minor complication were noted. Among the risk factors, the odds for failure after peripheral artery disease was 10.99 (p = 0.035), and that associated with a history of amputation was 9.44 (0.0006). Other factors had no correlation with flap loss, including cases with no or one major vessel. Flap survival rate was 90.5 percent, and the overall limb salvage rate was 93.7 percent. CONCLUSIONS: Despite the high risk of failure related to peripheral artery disease and history of amputation, the supermicrosurgery approach using a recipient vessel with good pulsation regardless of the source can achieve limb salvage. This approach extends the possibility for reconstruction in patients with severe ischemic diabetic foot. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 27673542 TI - The Concepts of Propeller, Perforator, Keystone, and Other Local Flaps and Their Role in the Evolution of Reconstruction. AB - LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the history and physiology of perforator flaps. 2. Understand the concept of "free-style" perforator flaps and principles in design and harvest. 3. Understand the uses of perforator flaps in reconstruction and applications in new settings. 4. Understand new principles in single and multiple perforator flap harvest and adjunct techniques that can be used in perforator flaps. 5. Highlight pertinent anatomy and techniques for selected perforator flaps described. SUMMARY: Extended knowledge of vascular anatomy has propagated the development of perforator flaps, which preserve muscle function and reduce morbidity. This has been achieved through the exemplary works of Manchot, Salmon, Milton, Taylor, and many others. With over 350 clinically relevant perforators in the body, this has created new flap options and a sense of creative freedom for reconstruction tailored toward a specific defect, without constraints of specific landmarks and using a "free-style" approach. Dominant perforators may be found in zones of high perforator density or "hot spots," which can help to conceptualize local flap options and aid flap design. This article aims to outline the history, physiology, and principles of flap design and harvest, and highlight traditional and evolving concepts and modifications of contemporary and traditional flaps that are changing reconstructive practice. This is a broad overview focusing on clinical applications, highlighting key concepts in a selection of new or evolving flaps being used in clinical practice and providing source references to acquire detailed flap descriptions. PMID- 27673543 TI - Computer Simulation and Digital Resources for Plastic Surgery Psychomotor Education. AB - Contemporary plastic surgery residents are increasingly challenged to learn a greater number of complex surgical techniques within a limited period. Surgical simulation and digital education resources have the potential to address some limitations of the traditional training model, and have been shown to accelerate knowledge and skills acquisition. Although animal, cadaver, and bench models are widely used for skills and procedure-specific training, digital simulation has not been fully embraced within plastic surgery. Digital educational resources may play a future role in a multistage strategy for skills and procedures training. The authors present two virtual surgical simulators addressing procedural cognition for cleft repair and craniofacial surgery. Furthermore, the authors describe how partnerships among surgical educators, industry, and philanthropy can be a successful strategy for the development and maintenance of digital simulators and educational resources relevant to plastic surgery training. It is our responsibility as surgical educators not only to create these resources, but to demonstrate their utility for enhanced trainee knowledge and technical skills development. Currently available digital resources should be evaluated in partnership with plastic surgery educational societies to guide trainees and practitioners toward effective digital content. PMID- 27673544 TI - Microsurgery Workout: A Novel Simulation Training Curriculum Based on Nonliving Models. AB - BACKGROUND: Currently, there are no valid training programs based solely on nonliving models. The authors aimed to develop and validate a microsurgery training program based on nonliving models and assess the transfer of skills to a live rat model. METHODS: Postgraduate year-3 general surgery residents were assessed in a 17-session program, performing arterial and venous end-to-end anastomosis on ex vivo chicken models. Procedures were recorded and rated by two blinded experts using validated global and specific scales (objective structured assessment of technical skills) and a validated checklist. Operating times and patency rates were assessed. Hand-motion analysis was used to measure economy of movements. After training, residents performed an arterial and venous end-to-end anastomosis on live rats. Results were compared to six experienced surgeons in the same models. Values of p < 0.05 were considered statistically significant. RESULTS: Learning curves were achieved. Ten residents improved their median global and specific objective structured assessment of technical skills scores for artery [10 (range, 8 to 10) versus 28 (range, 27 to 29), p < 0.05; and 8 (range, 7 to 9) versus 28 (range, 27 to 28), p < 0.05] and vein [8 (range, 8 to 11) versus 28 (range, 27 to 28), p < 0.05; and 8 (range, 7 to 9) versus 28 (range, 27 to 29), p < 0.05]. Checklist scores also improved for both procedures (p < 0.05). Trainees were slower and less efficient than experienced surgeons (p < 0.05). In the living rat, patency rates at 30 minutes were 100 percent and 50 percent for artery and vein, respectively. CONCLUSIONS: Significant acquisition of microsurgical skills was achieved by trainees to a level similar to that of experienced surgeons. Acquired skills were transferred to a more complex live model. PMID- 27673545 TI - Systematic Review of Liposomal Bupivacaine (Exparel) for Postoperative Analgesia. AB - BACKGROUND: Management of postoperative pain often requires multimodal approaches. Suboptimal dosages of current therapies can leave patients experiencing periods of insufficient analgesia, often requiring rescue therapy. With absence of a validated and standardized approach to pain management, further refinement of treatment protocols and targeted therapeutics is needed. Liposomal bupivacaine (Exparel) is a longer acting form of traditional bupivacaine that delivers the drug by means of a multivesicular liposomal system. The effectiveness of liposomal bupivacaine has not been systematically analyzed relative to conventional treatments in plastic surgery. METHODS: A comprehensive literature search of the MEDLINE, PubMed, and Google Scholar databases was conducted for studies published through October of 2015 with search terms related to liposomal bupivacaine and filtered for relevance to postoperative pain control in plastic surgery. Data on techniques, outcomes, complications, and patient satisfaction were collected. RESULTS: A total of eight articles were selected and reviewed from 160 identified. Articles covered a variety of techniques using liposomal bupivacaine for postoperative pain management. Four hundred five patients underwent procedures (including breast reconstruction, augmentation mammaplasty, abdominal wall reconstruction, mastectomy, and abdominoplasty) where pain was managed with liposomal bupivacaine and compared with those receiving traditional pain management. Liposomal bupivacaine use showed adequate safety and tolerability and, compared to traditional protocols, was equivalent or more effective in postoperative pain management. CONCLUSION: Liposomal bupivacaine is a safe method for postoperative pain control in the setting of plastic surgery and may represent an alternative to more invasive pain management systems such as patient-controlled analgesia, epidurals, peripheral nerve catheters, or intravenous narcotics. PMID- 27673546 TI - Reply: Does the Eyebrow Sag with Aging? An Anthropometric Study of 95 Caucasians from 20 to 79 Years of Age. PMID- 27673547 TI - Reply: Aspiration of Periprosthetic Seromas Using the Blunt SeromaCath. PMID- 27673548 TI - Nonmucinous Biliary Epithelium Is a Frequent Finding and Is Often the Predominant Epithelial Type in Mucinous Cystic Neoplasms of the Pancreas and Liver. AB - Mucinous cystic neoplasms (MCNs) can occur in the pancreas and liver. Classically, these cystic lesions are lined by columnar mucinous epithelium with underlying ovarian-type stroma. It has been proposed that cysts with ovarian-type stroma and nonmucinous epithelium be considered separate entities in both the pancreas and liver. Using a series of 104 pancreatic and 32 hepatic cases, we aimed to further characterize the epithelium present in MCNs. Mucinous epithelium was defined as pancreatic intraepithelial neoplasia-like columnar cells with pale pink/clear apical mucin. Epithelial cells ranging from flat to cuboidal to short columnar without obvious mucin or goblet cells were classified as nonmucinous/biliary epithelium. A mixture (at least 5%) of mucinous and nonmucinous/biliary epithelium was noted in 81%. Almost half (47%) of the cases had abundant (>50%) nonmucinous/biliary epithelium. Of the 71 cases with <=50% nonmucinous/biliary epithelium, 8 cases demonstrated high-grade dysplasia (7 pancreas, 1 liver) and 14 demonstrated invasive adenocarcinoma (11 pancreas, 3 liver). Conversely, of the 58 cases with >50% nonmucinous/biliary epithelium, not a single case of high-grade dysplasia (P=0.007) or invasive carcinoma (P<0.001) was identified. In summary, nonmucinous/biliary epithelium frequently occurs in MCNs of the pancreas and liver. As mucinous and nonmucinous/biliary epithelia often occur together, there does not appear to be enough evidence to regard cases with predominantly nonmucinous/biliary epithelium as separate entities. Our findings suggest that mucinous change is a "progression" phenomenon in MCNs of the pancreas and liver, and only when abundant mucinous epithelium is present is there a risk of progression to malignancy. PMID- 27673549 TI - Echinococcosis: Unexpected Occurrence and the Diagnostic Contribution of Routine Histopathology. AB - Echinococcus is the smallest of the major tapeworms. Humans are incidental hosts who become infected by exposure to soil contaminated with ova from the feces of the canine definitive hosts. The major species are E. granulosus (cystic echinococcosis) and E. multilocularis (alveolar or sylvatic echinococcosis), both common worldwide but unusual and not reportable in the United States. Human disease is characterized by slowly growing visceral cystic masses often containing daughter cysts and hydatid sand. In nonendemic areas, the clinical evaluation includes imaging, serology, and surgery; metastatic tumor is a major consideration. The diagnosis depends on the morphologic recognition of scolices and hooklets, albeit degenerated, within the cyst or attached to the cyst wall. Highly suggestive cyst wall features are an acellular hyaline lining surrounded by focally calcific fibrous tissue and chronic inflammation. We report 7 patients encountered in the Chicago area (5 E. granulosus, 2 E. multilocularis) who presented with cystic masses affecting the liver, lung, soft tissue, and spleen. The initial diagnosis was established or suggested by intraoperative evaluation of cyst fluid or cyst wall histopathology. Organism parts were found in 5 cases; 1 patient had a hyalinized cyst wall with a positive IgG (enzyme-linked immunosorbent assay), and 1 had a positive Western blot and a 30-year history of treatment. Treatment included cyst resection, hepatic lobectomy, intraoperative cyst injection, and benzimidazole therapy. There was 1 death. In a nonendemic area, the awareness of the pathologist to the possibility of this disease will exclude a neoplasm and facilitate prompt antihelminthic treatment. PMID- 27673550 TI - From the Editor. PMID- 27673551 TI - "I think I became a swimmer rather than just someone with a disability swimming up and down:" paralympic athletes perceptions of self and identity development. AB - PURPOSE: The purpose of this study was to explore the role of swimming on Paralympic athletes' perceptions of self and identity development. METHOD: A hermeneutic phenomenological approach was taken. During semi-structured interviews, five Paralympic swimmers (aged 20-24 years) were asked questions about their swimming career, perceptions of self, integration, and impairment. Interviews were audio-recorded and transcribed verbatim. RESULTS: An Interpretative Phenomenological Analysis yielded three superordinate themes: (a) "One of the crowd"; none of the participants viewed themselves as disabled, nor as supercrips; these perceptions stemmed from family-, school-, and swimming related experiences, (b) "Becoming me"; participation in swimming facilitated self- and social-acceptance, and identity development, and c) "A badge of honor"; swimming presented opportunity to present and reinforce a positive identity. CONCLUSIONS: Swimming experiences enabled the participants to enhance personal and social identities, integrate through pro-social mechanisms, and to develop a career path following retirement from competition. Implications for rehabilitation Offering equal sporting opportunities for people with/without physical disability can help facilitate social integration and act as a buffer against stigmatization. Our research suggests that participation in sport had afforded the participants a heightened sense of self-concept, independence, ability and corresponding pride. When working with individuals with physical disabilities, rehabilitation professionals could utilize sport as a means of increasing an individual's feelings of independence, confidence and normalization. As such, part of rehabilitation should be to ensure opportunities for sport participation for people with physical disability are available for people of all ages. PMID- 27673552 TI - Sweet Potato Peels and Cancer Prevention. AB - A bioassay-guided fractionation of an alcoholic extract from the peels of Ipomoea batatas Lam has been carried out. Sulforhodamine B and 2,2-diphenyl-1 picrylhydrazyl (DPPH) assays were used to evaluate the anticancer and antioxidant potential, respectively, while silica gel column chromatography (CC) was used to isolate compounds that were characterized using 1D- and 2D-NMR (Nuclear Magnetic Resonance) and mass spectrometry. The alcoholic extract was fractionated into n hexane, ethyl acetate, n-butanol, and water. The n-hexane fraction which showed the most promising anticancer activity was further fractionated via silica gel CC into IB-F002A, IB-F002B, and IB-F002C. Of these, IB-F002C was the most active with IC50 values 24.75, 47.91, 52.37, 34.17, 46.07, and 25.89 MUg/ml against breast, colon-1, colon-2, ovary, lung, and head/neck cancer cell lines, respectively. The bioassay-guided isolation from IB-F002C afforded a glucocerebroside, which showed 10.51%, 12.19%, 16.14%, and 34.05% inhibition of head and neck, breast-1, colon-1, and ovarian cancer cell lines, respectively. Octadecyl coumarate, 7-hydroxycoumarin, and 6-methoxy-7-hydroxycoumarin that showed different antioxidant potentials were also identified in this study. Sweet potato peel, which is usually discarded as waste, contains constituents that can serve as dietary components to prevent the development of different types of cancer. PMID- 27673553 TI - Regulated and Functional Expression of the Corepressor MTA3 in Rodent Testis. AB - Metastasis-associated protein (MTA)3 is a subunit of the Mi-2/nucleosome remodeling and deacetylase protein complex, with relevant roles in the regulation of cancerous epithelial to mesenchymal transition in an estrogen-dependent manner, recently involved in the modulation of different physiological processes. Although these findings connect MTA3 expression with hormonal signaling in various systems, little is known about whether this relationship is conserved in testis where hormonal action is intensive. We, therefore, document here for the first time the expression of Mta3/MTA3 in mammalian testes, where MTA3 protein was identified mainly in interstitial Leydig cells. Testicular levels of Mta3/MTA3 were overtly modulated by pituitary gonadotropins, as well as metabolic signals, such as dexamethasone, T4, and rosiglitazone. In addition, ablation of endogenous Mta3 by short hairpin RNA significantly inhibited human choriogonadotropin/dibutyryl-cAMP (db-cAMP)-stimulated progesterone secretion in MA-10 Leydig cells, whereas overexpression of exogenous MTA3 effectively reversed Mta3 deficiency damaged progesterone production. Moreover, attenuated Mta3 expression positively correlated to the deregulated level of serum testosterone in murine type 2 diabetes mellitus. From a functional standpoint, MTA3 deficiency was involved in insulin-mediated inhibition of testicular steroidogenesis. Our data are the first to disclose the presence and functional role of MTA3 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues and is closely associated with steroidogenic dysfunction. The current study expands the reproductive dimension of MTA3, which may operate directly at the testicular level to modulate steroidogenic function. PMID- 27673554 TI - Osteocalcin and Sex Hormone Binding Globulin Compete on a Specific Binding Site of GPRC6A. AB - The undercarboxylated form of osteocalcin (ucOC) regulates male fertility and energy metabolism, acting through the G protein-coupled receptor (GPRC)6A, thus forming a new pancreas-bone-testis axis. Recently, GPRC6A has also been suggested to mediate the nongenomic responses of free testosterone (T). However, these data did not consider the physiological scenario, where circulating T is mainly bound to sex hormone-binding globulin (SHBG) and only a small percentage circulates freely in the blood. Here, by the use of computational modelling, we document the existence of similar structural moieties between ucOC and SHBG that are predicted to bind to GPRC6A at docking analysis. This hypothesis of competition was assessed by binding experiments on human embryonic kidney-293 cells transfected with human GPRC6A gene. Unliganded SHBG specifically bound the membrane of human embryonic kidney-293 cells transfected with GPRC6A and was displaced by ucOC when coincubated at 100-fold molar excess. Furthermore, specific downstream Erk1/2 phosphorylation after stimulation of GPRC6A with ucOC was significantly blunted by 100-fold molar excess of unliganded SHBG. Intriguingly previous incubation with unliganded SHBG, followed by incubation with T, induced Erk1/2 phosphorylation in a dose-dependent manner. Neither binding nor stimulating activities were shown for SHBG saturated with T. Experiments on mutation constructs of GPRC6A strengthened the hypothesis of a common binding site of ucOC and SHBG. Given the role of GPRC6A on energy metabolism, these data agree with epidemiological association between SHBG levels and insulin sensitivity, suggest GPRC6A as a likely SHBG receptor, and add bases for the possible regulation of androgen activity in a nonsteroidal manner. PMID- 27673556 TI - Cyclic AMP Effectors Regulate Myometrial Oxytocin Receptor Expression. AB - The factors that initiate human labor are poorly understood. We have tested the hypothesis that a decline in cAMP/protein kinase A (PKA) function leads to the onset of labor. Initially, we identified myometrial cAMP/PKA-responsive genes (six up-regulated and five down-regulated genes) and assessed their expression in myometrial samples taken from different stages of pregnancy and labor. We found that the oxytocin receptor (OTR) was one of the cAMP-repressed genes, and, given the importance of OTR in the labor process, we studied the mechanisms involved in greater detail using small interfering RNA, chemical agonists, and antagonists of the cAMP effectors. We found that cAMP-repressed genes, including OTR, increased with the onset of labor. Our in vitro studies showed that cAMP acting via PKA reduced OTR expression but that in the absence of PKA, cAMP acts via exchange protein activated by cAMP (EPAC) to increase OTR expression. In early labor myometrial samples, PKA levels and activity declined and Epac1 levels increased, perhaps accounting for the increase in myometrial OTR mRNA and protein levels at this time. In vitro exposure of myometrial cells to stretch and IL-1beta increased OTR levels and reduced basal and forskolin-stimulated cAMP and PKA activity, as judged by phospho-cAMP response element-binding protein levels, but neither stretch nor IL-1beta had any effect on PKA or EPAC1 levels. In summary, there is a reduction in the activity of the cAMP/PKA pathway with the onset of human labor potentially playing a critical role in regulating OTR expression and the transition from myometrial quiescence to activation. PMID- 27673557 TI - The Double-Edged Sword - Outward and Inward Directed Aggression among War Combatants. AB - Inspired by the two-stage model of countervailing forces, we explored the mechanism underlining inward and outward aggression among ex-combatants. Israeli veterans (N = 230) reported their partner's violence (outward aggression), suicidal ideation (inward aggression), aggressive impulses, posttraumatic stress disorder (PTSD), paranoid ideation and guilt. Suicidal ideation was related to aggressive impulses only in the presence of PTSD, or under high guilt; whereas paranoid ideation buffered these effects. Violence towards the partner, on the other hand, was related to aggressive impulses under low guilt and in the absence of PTSD. Aggressive impulses underline both suicidal ideation and partner violence. The inter-relations between PTSD, guilt, and paranoid ideation influence the manifestation of aggression and the direction it takes. PMID- 27673555 TI - Excess Testosterone Exposure Alters Hypothalamic-Pituitary-Testicular Axis Dynamics and Gene Expression in Sheep Fetuses. AB - Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P < .05) serum LH concentrations and reduced the expression of gonadotropin subunit mRNA in both sexes and the levels of GnRH receptor mRNA in males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reduced mRNA levels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P < .01) in control females than in males and reduced (P < .001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor-beta, and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life. PMID- 27673559 TI - Safety of Intra-Articular Implantation of Oligo[Poly(ethylene glycol) Fumarate] Scaffolds into the Rabbit Knee. AB - Implantable biomaterials supporting extended release of pharmacologic agents may permit localized intra-articular delivery of drugs that modulate the fibrotic response to injuries and surgery. Oligo[poly (ethylene glycol)] fumarate (OPF) is an attractive organic carrier, but its safety profile within synovial joints remains unclear. Here, we assessed the safety of OPF sponges using a validated in vivo model of knee arthrofibrosis. A cohort of 102 rabbits was divided into five groups: arthrotomy only (24), arthrotomy with OPF scaffold placement (24), surgically induced contracture (24), surgically induced contracture with OPF scaffold placement (24), and control without any surgical intervention (6). Six rabbits per surgical group were sacrificed at 72 h, 2, 8, and 24 weeks. Outcomes included biomechanical testing of range of motion, histologic analysis of synovial and cartilage tissues, and scaffold degradation. Cartilage histology and biomechanical measurements were comparable between groups with and without OPF. Synovial inflammation scores were similar among most groups with a minimally elevated score in the rabbits with arthrotomy and OPF versus those with arthrotomy alone. Scores for synovial tissues in rabbits with contracture and OPF were clinically equivalent to those with contractures alone. Most animals (92%) retained scaffold fragments at 24 weeks. Thus, OPF scaffolds implanted into native or arthrofibrotic rabbit knees neither induce nor aggravate cartilage damage, synovial inflammation, or contractures. The apparent safety of OPF scaffolds suggests that they are suitable carriers for the controlled delivery of reagents into the intra-articular joint space to treat arthrofibrosis. PMID- 27673558 TI - Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer. AB - Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer. PMID- 27673561 TI - For better or for worse, UV in psoriasis. PMID- 27673562 TI - Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments. AB - No independent cross-validation of success rate for studies utilizing small interfering RNA (siRNA) for gene silencing has been completed before. To assess the influence of experimental parameters like cell line, transfection technique, validation method, and type of control, we have to validate these in a large set of studies. We utilized gene chip data published for siRNA experiments to assess success rate and to compare methods used in these experiments. We searched NCBI GEO for samples with whole transcriptome analysis before and after gene silencing and evaluated the efficiency for the target and off-target genes using the array based expression data. Wilcoxon signed-rank test was used to assess silencing efficacy and Kruskal-Wallis tests and Spearman rank correlation were used to evaluate study parameters. All together 1,643 samples representing 429 experiments published in 207 studies were evaluated. The fold change (FC) of down regulation of the target gene was above 0.7 in 18.5% and was above 0.5 in 38.7% of experiments. Silencing efficiency was lowest in MCF7 and highest in SW480 cells (FC = 0.59 and FC = 0.30, respectively, P = 9.3E-06). Studies utilizing Western blot for validation performed better than those with quantitative polymerase chain reaction (qPCR) or microarray (FC = 0.43, FC = 0.47, and FC = 0.55, respectively, P = 2.8E-04). There was no correlation between type of control, transfection method, publication year, and silencing efficiency. Although gene silencing is a robust feature successfully cross-validated in the majority of experiments, efficiency remained insufficient in a significant proportion of studies. Selection of cell line model and validation method had the highest influence on silencing proficiency. PMID- 27673560 TI - A potential role for genome structure in the translation of mechanical force during immune cell development. AB - Immune cells react to a wide range of environments, both chemical and physical. While the former has been extensively studied, there is growing evidence that physical and in particular mechanical forces also affect immune cell behavior and development. In order to elicit a response that affects immune cell behavior or development, environmental signals must often reach the nucleus. Chemical and mechanical signals can initiate signal transduction pathways, but mechanical forces may also have a more direct route to the nucleus, altering nuclear shape via mechanotransduction. The three-dimensional organization of DNA allows for the possibility that altering nuclear shape directly remodels chromatin, redistributing critical regulatory elements and proteins, and resulting in wide scale gene expression changes. As such, integrating mechanotransduction and genome architecture into the immunology toolkit will improve our understanding of immune development and disease. PMID- 27673563 TI - Ecdysone Receptor-based Singular Gene Switches for Regulated Transgene Expression in Cells and Adult Rodent Tissues. AB - Controlled gene expression is an indispensable technique in biomedical research. Here, we report a convenient, straightforward, and reliable way to induce expression of a gene of interest with negligible background expression compared to the most widely used tetracycline (Tet)-regulated system. Exploiting a Drosophila ecdysone receptor (EcR)-based gene regulatory system, we generated nonviral and adenoviral singular vectors designated as pEUI(+) and pENTR-EUI, respectively, which contain all the required elements to guarantee regulated transgene expression (GAL4-miniVP16-EcR, termed GvEcR hereafter, and 10 tandem repeats of an upstream activation sequence promoter followed by a multiple cloning site). Through the transient and stable transfection of mammalian cell lines with reporter genes, we validated that tebufenozide, an ecdysone agonist, reversibly induced gene expression, in a dose- and time-dependent manner, with negligible background expression. In addition, we created an adenovirus derived from the pENTR-EUI vector that readily infected not only cultured cells but also rodent tissues and was sensitive to tebufenozide treatment for regulated transgene expression. These results suggest that EcR-based singular gene regulatory switches would be convenient tools for the induction of gene expression in cells and tissues in a tightly controlled fashion. PMID- 27673564 TI - miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPalpha. AB - Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-alpha (C/EBPalpha) is a potential target of miR 181a and luciferase assay confirmed that KLF6 and C/EBPalpha translation is suppressed by miR-181a through interaction with the 3'UTR of KLF6 and C/EBPalpha mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPalpha protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPalpha. PMID- 27673565 TI - Telemedicine-Assisted Intubation in Rural Emergency Departments: A National Emergency Airway Registry Study. AB - BACKGROUND: Intubation in rural emergency departments (EDs) is a high-risk procedure, often with little or no specialty support. Rural EDs are utilizing real-time telemedicine links, connecting providers to an ED physician who may provide clinical guidance. INTRODUCTION: We endeavored to describe telemedicine assisted intubation in rural EDs that are served by an ED telemedicine network. MATERIALS AND METHODS: Prospective data were collected on all patients who had an intubation attempt while on the video telemedicine link from May 1, 2014 to April 30, 2015. We report demographic information, indication, methods, number of attempts, operator characteristics, telemedicine involvement/intervention, adverse events, and clinical outcome by using descriptive statistics. RESULTS: Included were 206 intubations. The most common indication for intubation was respiratory failure. First-pass success rate (postactivation) was 71%, and 96% were eventually intubated. Most attempts (66%) used rapid-sequence intubation. Fifty-four percent of first attempts used video laryngoscopy (VL). Telemedicine providers intervened in 24%, 43%, and 55% of first-third attempts, respectively. First-pass success with VL and direct laryngoscopy was equivalent (70% vs. 71%, p = 0.802). Adverse events were reported in 49 cases (24%), which were most frequently hypoxemia. DISCUSSION: The impact of telemedicine during emergency intubation is not defined. We showed a 71% first-pass rate post-telemedicine linkage (70% of cases had a previous attempt). Our ultimate success rate was 96%, similar to that in large-center studies. Telemedicine support may contribute to success. CONCLUSIONS: Telemedicine-supported endotracheal intubation performed in rural hospitals is feasible, with good success rates. Future research is required to better define the impact of telemedicine providers on emergency airway management. PMID- 27673566 TI - Next generation sequencing data of a defined microbial mock community. AB - Generating sequence data of a defined community composed of organisms with complete reference genomes is indispensable for the benchmarking of new genome sequence analysis methods, including assembly and binning tools. Moreover the validation of new sequencing library protocols and platforms to assess critical components such as sequencing errors and biases relies on such datasets. We here report the next generation metagenomic sequence data of a defined mock community (Mock Bacteria ARchaea Community; MBARC-26), composed of 23 bacterial and 3 archaeal strains with finished genomes. These strains span 10 phyla and 14 classes, a range of GC contents, genome sizes, repeat content and encompass a diverse abundance profile. Short read Illumina and long-read PacBio SMRT sequences of this mock community are described. These data represent a valuable resource for the scientific community, enabling extensive benchmarking and comparative evaluation of bioinformatics tools without the need to simulate data. As such, these data can aid in improving our current sequence data analysis toolkit and spur interest in the development of new tools. PMID- 27673567 TI - Plasma apelin-13, attention-deficit hyperactivity disorder, and environmental exposure to nitrous oxide. PMID- 27673568 TI - Intrarater Reliability of Tonometry and Bioimpedance Spectroscopy to Measure Tissue Compressibility and Extracellular Fluid in the Legs of Healthy Young People in Australia and Myanmar. AB - BACKGROUND: Measurements of tissue compressibility and extracellular fluid (ECF) are used to monitor progression of lymphedema, a chronic swelling of the subcutaneous tissue. Later stages of lymphedema are characterized by fibrotic induration in the subcutis and hyperkeratosis of the skin. Several devices are available to measure these changes, but previous reliability and validity studies have been conducted primarily on adult women with unilateral arm lymphedema using contralateral limbs as controls. To date, no studies have included either adolescents or measurement of leg tissue. METHODS AND RESULTS: An intrarater reliability study was conducted to compare three devices measuring skin and subcutaneous tissue compressibility; a mechanical Tonometer, a digital Indurometer, and a SkinFibroMeter. ECF loads were measured using bioimpedance spectroscopy (BIS). Two populations of tropical-dwelling young people were included; Australian residents in North Queensland aged 8-21 years (n = 34) and people aged 10-21 years residing in Central Myanmar (n = 38). Neither cohort had any clinical sign of lymphedema or other leg abnormality. The mechanical Tonometer and the digital Indurometer had excellent intraclass correlation coefficient (ICC) scores between 0.792 (95% CI 0.055-0.901) and 0.964 (95% CI 0.945-0.984) and the SkinFibroMeter had good to excellent reliability with ICC scores of between 0.565 (95% CI 0.384-0.747) and 0.877 (95% CI 0.815-0.840). BIS exhibited the highest reliability with ICC scores approaching 1.0. CONCLUSIONS: These results support the reliable use of tonometry and BIS to assess tissue compressibility and ECF loads in the legs of adolescent populations in developed and developing tropical countries. PMID- 27673570 TI - Tracking Transient Conformational States of T4 Lysozyme at Room Temperature Combining X-ray Crystallography and Site-Directed Spin Labeling. AB - Proteins are dynamic molecules that can transiently adopt different conformational states. As the function of the system often depends critically on its conformational state a rigorous understanding of the correlation between structure, energetics and dynamics of the different accessible states is crucial. The biophysical characterization of such processes is, however, challenging as the excited states are often only marginally populated. We show that a combination of X-ray crystallography performed at 100 K as well as at room temperature and EPR spectroscopy on a spin-labeled single crystal allows to correlate the structures of the ground state and a thermally excited state with their thermodynamics using the variant 118R1 of T4 lysozyme as an example. In addition, it is shown that the surrounding solvent can significantly alter the energetic as well as the entropic contribution to the Gibbs free energy without major impact on the structure of both states. PMID- 27673571 TI - Chemical Strategy to Stepwise Amplification of Signals in Surface Plasmon Resonance Imaging Detection of Saccharides and Glycoconjugates. AB - A stepwise strategy was proposed to controllably amplify surface plasmon resonance imaging (SPRi) signals and used to establish a method for sensitive detection of small saccharides and large glycoconjugates. The key is to enlarge the target analytes step by step through a cyclic recognition reaction of concanavalin A (ConA) with dextran, which can easily be integrated into SPRi detection. The reaction is theoretically expected to proceed with infinite cycles by addition of ConA and dextran one after another, and in practice, it allows for performing signal amplification for up to 20 steps, which nearly reaches the limit of the propagation depth of surface plasmon waves. Because of the nonspecific adsorption effect, the maximum signals of small sugars were measured at steps 5-7 by the use of small molecules like ethanol amine to block the nonspecific adsorption. The real applicability of the method was validated by SPRi determination of either immobilized saccharides and glycoproteins or captured carcinoembryonic antigen (CEA) from patient samples with a limit of detection down to 2.5 MUM glucose or 50 pg/mL of CEA. A wide extendibility of the method was confirmed by detecting other ConA-recognizable analytes like human IgG, ovalbumin, alpha-fetoprotein, and analytes convertible to ConA- or dextran recognizable forms. Notably, other cyclic reactions specific to saccharides or other analytes are in theory exploitable, which will further widen the applicability of the method and strategy. PMID- 27673572 TI - Precisely Controllable Core-Shell Ag@Carbon Dots Nanoparticles: Application to in Situ Super-Sensitive Monitoring of Catalytic Reactions. AB - Carbon dots (CDs) have attracted extensive interest owing to their unparalleled physical and chemical characteristics. CDs based nanocomposites have also drawn increasing attention because the combination of different characteristics could offer additional brilliant properties (such as photocatalysis and Raman scattering). In this work, we developed a fast, facile, and controllable method for fabricating core-shell Ag@CDs nanoparticles (NPs) based on the ability of CDs to directly reduce Ag+ to Ag NPs without an external photoirradiation process or additional reductants. The as-prepared Ag@CDs NPs caused efficient CDs fluorescence quenching, and the typical bands of carbon species were obtained in the Raman spectrum of CDs. In addition, we found that the Ag@CDs NPs could be utilized as an efficient surface-enhanced Raman scattering (SERS) substrate, showing a discernible detection concentration as low as 10-8 M by using p aminothiophenol (PATP) as the probe molecules. The as-prepared Ag@CDs NPs used as the SERS substrate also exhibited excellent peroxidase-like catalytic activity for in situ super-sensitive monitoring of the oxidation of 3,3',5,5' tetramethylbenzidine by H2O2, a plasmon-enhanced driven photocatalytic reaction of p-nitrothiophenol (PNTP) dimerizing into 4,4'-dimercaptoazobenzene, and catalytic driven reduction of PNTP to PATP in the presence of NaBH4 in real time. Moreover, the determination of H2O2 with a significantly lower discernible detection concentration was obtained. This work demonstrated that the hybrid nanostructures not only exhibited unique SERS properties but also showed excellent catalytic activities, especially as an ultrasensitive SERS substrate for monitoring heterogeneous catalytic reactions in real time. This would make it possible to not only obtain the information about catalytic molecular changes but also conduct quantitative and qualitative analysis, and widen the application of CDs in SERS and catalytic reactions. PMID- 27673569 TI - Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury. AB - Restoration of walking ability is an area of great interest in the rehabilitation of persons with spinal cord injury. Because many cortical, subcortical, and spinal neural centers contribute to locomotor function, it is important that intervention strategies be designed to target neural elements at all levels of the neuraxis that are important for walking ability. While to date most strategies have focused on activation of spinal circuits, more recent studies are investigating the value of engaging supraspinal circuits. Despite the apparent potential of pharmacological, biological, and genetic approaches, as yet none has proved more effective than physical therapeutic rehabilitation strategies. By making optimal use of the potential of the nervous system to respond to training, strategies can be developed that meet the unique needs of each person. To complement the development of optimal training interventions, it is valuable to have the ability to predict future walking function based on early clinical presentation, and to forecast responsiveness to training. A number of clinical prediction rules and association models based on common clinical measures have been developed with the intent, respectively, to predict future walking function based on early clinical presentation, and to delineate characteristics associated with responsiveness to training. Further, a number of variables that are correlated with walking function have been identified. Not surprisingly, most of these prediction rules, association models, and correlated variables incorporate measures of volitional lower extremity strength, illustrating the important influence of supraspinal centers in the production of walking behavior in humans. PMID- 27673573 TI - Osteocyte physiology and response to fluid shear stress are impaired following exposure to cobalt and chromium: Implications for bone health following joint replacement. AB - The effects of metal ion exposure on osteocytes, the most abundant cell type in bone and responsible for coordinating bone remodeling, remain unclear. However, several studies have previously shown that exposure to cobalt (Co2+ ) and chromium (Cr3+ ), at concentrations equivalent to those found clinically, affect osteoblast and osteoclast survival and function. In this study, we tested the hypothesis that metal ions would similarly impair the normal physiology of osteocytes. The survival, dendritic morphology, and response to fluid shear stress of the mature osteocyte-like cell-line MLO-Y4 following exposure to clinically relevant concentrations and combinations of Co and Cr ions were measured in 2D-culture. Exposure of MLO-Y4 cells to metal ions reduced cell number, increased dendrites per cell and increased dendrite length. We found that combinations of metal ions had a greater effect than the individual ions alone, and that Co2+ had a predominate effect on changes to cell numbers and dendrites. Combined metal ion exposure blunted the responses of the MLO-Y4 cells to fluid shear stress, including reducing the intracellular calcium responses and modulation of genes for the osteocyte markers Cx43 and Gp38, and the signaling molecules RANKL and Dkk-1. Finally, we demonstrated that in the late osteoblasts/early osteocytes cell line MLO-A5 that Co2+ exposure had no effect on mineralization, but Cr3+ treatment inhibited mineralization in a dose-dependent manner, without affecting cell viability. Taken together, these data indicate that metal exposure can directly affect osteocyte physiology, with potential implications for bone health including osseointegration of cementless components, and periprosthetic bone remodeling. (c) 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1716-1723, 2017. PMID- 27673574 TI - Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia. AB - Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway. PMID- 27673575 TI - Knowledge Gaps in Cardiovascular Care of Older Adults: A Scientific Statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society: Executive Summary. AB - The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease (CVD) is the leading cause of death and major disability in adults aged 75 and older. Despite the effect of CVD on quality of life, morbidity, and mortality in older adults, individuals aged 75 and older have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older adults with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in nursing homes and assisted living facilities. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older adults typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision-making, and recommend future research to close existing knowledge gaps. To achieve these objectives, a detailed review was conducted of current American College of Cardiology/American Heart Association (ACC/AHA) and American Stroke Association (ASA) guidelines to identify content and recommendations that explicitly targeted older adults. A pervasive lack of evidence to guide clinical decision-making in older adults with CVD was found, as well as a paucity of data on the effect of diagnostic and therapeutic interventions on outcomes that are particularly important to older adults, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older adults representative of those seen in clinical practice and that incorporate relevant outcomes important to older adults in the study design. The results of these studies will provide the foundation for future evidence-based guidelines applicable to older adults and enhance person-centered care of older individuals with CVD in the United States and around the world. PMID- 27673576 TI - Fatty acids profiling reveals potential candidate markers of semen quality. AB - Previous reports showed altered fatty acid content in subjects with altered sperm parameters compared to normozoospermic individuals. However, these studies focused on a limited number of fatty acids, included a short number of subjects and results varied widely. We conducted a case-control study involving 155 patients allocated into four groups, including normozoospermia (n = 33), oligoasthenoteratozoospermia (n = 32), asthenozoospermia (n = 25), and varicocoele (n = 44). Fatty acid profiling, including 30 species, was analyzed by a validated gas chromatography (GC) method on the whole seminal fluid sample. Multinomial logistic regression modeling was used to identify the associations between fatty acids and the four groups. Specimens from 15 normozoospermic subjects were also analyzed for fatty acids content in the seminal plasma and spermatozoa to study the distribution in the two compartments. Fatty acids lipidome varied markedly between the four groups. Multinomial logistic regression modeling revealed that high levels of palmitic acid, behenic acid, oleic acid, and docosahexaenoic acid (DHA) confer a low risk to stay out of the normozoospermic group. In the whole population, seminal fluid stearic acid was negatively correlated (r = -0.53), and DHA was positively correlated (r = 0.65) with sperm motility. Some fatty acids were preferentially accumulated in spermatozoa and the highest difference was observed for DHA, which was 6.2 times higher in spermatozoa than in seminal plasma. The results of this study highlight complete fatty acids profile in patients with different semen parameters. Given the easy-to-follow and rapid method of analysis, fatty acid profiling by GC method can be used for therapeutic purposes and to measure compliance in infertility trials using fatty acids supplements. PMID- 27673577 TI - A survey of the use of arterial catheters in anesthetized dogs and cats: 267 cases. AB - OBJECTIVES: To describe the clinical practice of insertion of arterial catheters in anesthetized dogs and cats, to document complications of arterial catheterization, and to determine risk factors associated with the complications. DESIGN: Prospective clinical study and retrospective evaluation of medical records. SETTING: University teaching hospital. ANIMALS: Dogs (n = 251) and 13 cats anesthetized for clinical procedures with arterial catheters inserted for blood pressure monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Details of the animal and catheter were collected at the time of anesthesia. On the following day, the catheter site was palpated and observed for abnormalities and the medical records of all animals were reviewed retrospectively for complications. Details of catheter placement were available for 216 catheters: 158 catheters in a dorsal pedal artery, 50 catheters in the median caudal (coccygeal) artery, 6 in the median artery, and 1 each in a cranial tibial and lingual artery. Blood pressure was obtained from 200 catheters, and 12 catheters failed before the end of anesthesia. Postoperative observational data obtained from 112 catheters described a palpable arterial pulse at 73 sites and no pulse at 21 sites. No risk factor for arterial occlusion was identified. No complications resulting from arterial catheterization were noted in the medical records. CONCLUSIONS: Arterial catheterization resulted in loss of a peripheral pulse postoperatively in 21/94 (22.3%) of animals examined, although no evidence of tissue ischemia was noted in the medical records of any of the patients in this study. These results suggest that insertion of a catheter in the dorsal pedal or coccygeal arteries was not associated with a high risk for complications. However, the course of arterial occlusion postoperatively warrants further investigation. PMID- 27673578 TI - A Synthesis of Exiguaquinol Dessulfate. AB - A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels-Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N-acyl hemiaminal, which was based upon an analysis of internal hydrogen-bonding interactions with polar functional groups, was proven correct. A late-stage intermediate did not demonstrate bactericidal activity against H. pylori cultures. PMID- 27673580 TI - Supramolecular Aggregates of Defined Stereochemical Scaffolds: Aggregation/Deaggregation in Schiff-Base Zinc(II) Complexes Derived from Enantiopure trans-1,2-Diaminocyclohexane. AB - This contribution explores, through detailed 1H NMR, DOSY NMR, optical absorption, and circular dichroism spectroscopic studies, the aggregation properties in solution of noncoordinating solvents of some new ZnII Schiff-base complexes, (R)-1, (S)-1, and (R)-2, derived from the chiral trans-1,2 diaminocyclohexane. It is found that chloroform solutions of 1 are characterized by the presence of three species, the predominance of which consists of large oligomeric aggregates. For chloroform solutions of 1, upon heating or standing, all species are irreversibly converted into a dimer, 1C, which is very stable and hardly disaggregable. Analysis of 1H NMR, UV/vis, and CD spectroscopic data and chemical evidence allow proposing a double helicate Zn2L2 structure with a tetrahedral coordination around the ZnII ions for 1C, as a consequence of the defined stereochemistry of the trans-1,2-diaminocyclohexane chelate bridge. This represents a different, uncommon aggregation mode in ZnII complexes of tetradentate Schiff-bases. PMID- 27673579 TI - Fludarabine and cytarabine versus high-dose cytarabine in consolidation treatment of t(8; 21) acute myeloid leukemia: A prospective, randomized study. AB - Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30-40% patients, with only 50-60% of patients with t(8;21) AML cured with regimens containing high-dose cytarabine (HD-Ara-C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD-Ara-C (n = 22). Our study showed that at 36-months, relapse free survival (RFS) was 81.73% in the FA arm and 50.73% in the HD-Ara-C arm (P = 0.04), overall survival (OS) was 91.1% and 48.4% (P = 0.01) in the FA arm and in the HD-Ara-C arm respectively; whereas cumulative incidence of relapse (CIR) was 18.27% and 47.39%, in the FA arm and in the HD-Ara-C arm respectively (P = 0.05). In our study, treatment with FA, MRD2 status (reduction >= 3-log) and absence of c-kit mutations were identified as independent prognostic factors for lower risk of relapse, improved RFS and OS. We also found RFS for patients without c-kit mutations was 100% in FA arm, and 57.8% in HD-Ara-C arm at 36 months (P = 0.005); OS of both groups at 36 months was 100% and 51.4%, respectively (P = 0.004), suggesting a benefit of consolidation therapy with FA for t(8;21) AML patients, especially, those without c-kit mutations (Clinicaltrials.org ID NCT# 02024308). Am. J. Hematol. 92:12-17, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27673581 TI - Takotsubo syndrome in the paediatric population: a case report and a systematic review. AB - We describe the case of a takotsubo syndrome in a 12-year-old male patient following an acute intracranial haemorrhage, which had a favourable outcome. We also performed a systematic review of published case reports in patients younger than 18 years. Although takotsubo syndrome is common in postmenopausal women, in the paediatric population it equally affects both sexes. Compared with adults, paediatric patients more commonly present with heart failure symptoms or loss of consciousness. A higher proportion of paediatric patients have ST segment depression on ECG. Moreover, in younger patients, a high proportion has nonapical anatomical variants and more severe left ventricular impairment. The increase in troponin and the decrease in left ventricular ejection fraction, the prevalence of neurological or psychological disorders, and in-hospital outcome are similar between adults and children. PMID- 27673583 TI - ? AB - Leadership in acute care teams based on knowledge and communication - an interdisciplinary analysis of a serie of in-situ trauma team trainings Efficient communication is one of the key features of good teamwork. Call-outs (CO) and Closed-loop communication (CLC), as a component of secure and efficient communication, has been extensively taught in the team training context. This paper reports results from a thesis exploring how trauma teams communicate while working. Eighteen in-situ trauma team training sessions were documented with surveys, audio and video for later analysis. Discourse analysis, quantitative content analysis and quantitative methods were used. The use of CO and CLC in the teams was low. CLC initiated by the team leader was associated with a higher likelihood of decision to go to surgery within the training session. CLC initiated by others than the team leaders was associated with longer time taken until the decision to go to definitive care. Using discourse analysis the leaders' way to position themselves using verbal communication could be described as dynamically switched between coercive, educational, discussing and negotiating strategies to take control of the team. Leaders that took control of the teams also positioned themselves physically in the inner circle, i.e. close to the patient's head. When trauma teams work together, only a limited amount of communication occurs structured as CO and CLC. The importance of physically positioning yourself at the right place in the room as well as to choose communication strategy to get things done might need to be discussed during leadership trainings. Deliberate practice in the use of communication tools as CO and CLC and in switching between different communication strategies might benefit the team function and the care of patients when time is sparse. PMID- 27673582 TI - Association Between Social Participation and 3-Year Change in Instrumental Activities of Daily Living in Community-Dwelling Elderly Adults. AB - OBJECTIVES: To investigate whether social participation (SP) in older adults is associated with ability to perform instrumental activities of daily living (IADLs). DESIGN: Prospective cohort study. SETTING: Two local municipalities of Nara, Japan. PARTICIPANTS: Individuals aged 65 to 96 (n = 2,774 male, n = 3,586 female) free of IADL disability at baseline. MEASUREMENTS: SP and IADLs were assessed using self-administered questionnaires. SP was categorized into five types and assessed using the number and type of social activities. IADLs were evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Logistic regression analysis stratified according to sex was used to examine change in IADLs according to SP, with nonparticipation as a reference. RESULTS: During the 3-year follow-up, 13.6% of men and 9.0% of women reported IADL decline. After adjusting for age, family structure, body mass index, pension, occupation, medical treatment, self-rated health, drinking, smoking, depression, cognitive function, and activities of daily living, participation in various social activities was inversely associated with change in IADLs in women but not men. Participation in the following types of social activities had significant inverse associations with IADL disability: hobby clubs (odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.49-0.94) for men and local events (OR = 0.68, 95% CI = 0.48-0.95), hobby clubs (OR = 0.53, 95% CI = 0.36-0.79), senior citizen clubs (OR = 0.74, 95% CI = 0.56-0.97), and volunteer groups (OR = 0.56, 95% CI = 0.32-0.99) for women. CONCLUSION: Participation in a variety of different types of social activities was associated with change in IADLs over the 3 years of this study in women, and participation in hobby clubs was associated with change in IADLs in men and women. Recommending that community-dwelling elderly adults participate in social activities appropriate for their sex may promote successful aging. PMID- 27673584 TI - ? PMID- 27673585 TI - ? PMID- 27673586 TI - ? PMID- 27673587 TI - ? PMID- 27673588 TI - ? PMID- 27673589 TI - ? PMID- 27673590 TI - ? PMID- 27673591 TI - ? PMID- 27673592 TI - ? PMID- 27673593 TI - ? PMID- 27673594 TI - ? PMID- 27673595 TI - ? PMID- 27673596 TI - Nonclassical Routes for Amide Bond Formation. AB - The present review offers an overview of nonclassical (e.g., with no pre- or in situ activation of a carboxylic acid partner) approaches for the construction of amide bonds. The review aims to comprehensively discuss relevant work, which was mainly done in the field in the last 20 years. Organization of the data follows a subdivision according to substrate classes: catalytic direct formation of amides from carboxylic and amines ( section 2 ); the use of carboxylic acid surrogates ( section 3 ); and the use of amine surrogates ( section 4 ). The ligation strategies (NCL, Staudinger, KAHA, KATs, etc.) that could involve both carboxylic acid and amine surrogates are treated separately in section 5 . PMID- 27673600 TI - Clinical Drug-Drug Interaction Studies: Methods, Pitfalls, and Interpretation. PMID- 27673597 TI - Targeted multimodal nano-reporters for pre-procedural MRI and intra-operative image-guidance. AB - Multimodal-imaging probes offer a novel approach, which can provide detail diagnostic information for the planning of image-guided therapies in clinical practice. Here we report targeted multimodal Nd3+-doped upconversion nanoparticle (UCNP) imaging reporters, integrating both magnetic resonance imaging (MRI) and real-time upconversion luminescence imaging (UCL) capabilities within a single platform. Nd3+-doped UCNPs were synthesized as a core-shell structure showing a bright visible emission upon excitation at the near infrared (minimizing biological overheating and increasing tissue penetration depth) as well as providing strong MRI T2 contrast (high r2/r1 ratio). Transcatheter intra-arterial infusion of Nd3+-doped UCNPs conjugated with anti-CD44-monoclonal antibody allowed for high performance in vivo multimodal UCL and MR imaging of hepatocellular carcinoma (HCC) in an orthotopic rat model. The resulted in vivo multimodal imaging of Nd3+ doped core-shell UCNPs combined with transcatheter intra-arterial targeting approaches successfully discriminated liver tumors from normal hepatic tissues in rats for surgical resection applications. The demonstrated multimodal UCL and MRI imaging capabilities of our multimodal UCNPs reporters suggest strong potential for in vivo visualization of tumors and precise surgical guidance to fill the gap between pre-procedural imaging and intraoperative reality. PMID- 27673598 TI - Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers. AB - This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for alpha-d-glucose is composed of 201 EQ and 435 TS conformers and that for beta-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of 1C4 and 4C1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of 4C1 conformations; that is, the potential energy of the global minimum of 4C1 is lower than that of 1C4 (thermodynamic predominance) and that the highest energy of those of all the TS structures along a route from 4C1 to 1C4 is lower than that of 1C4 to 4C1 (kinetic predominance). PMID- 27673601 TI - Experience from Development of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Dulaglutide for Treatment of Type 2 Diabetes Mellitus. PMID- 27673599 TI - The Arabidopsis heat-intolerant 5 (hit5)/enhanced response to aba 1 (era1) mutant reveals the crucial role of protein farnesylation in plant responses to heat stress. AB - Protein farnesylation is a post-translational modification known to regulate abscisic acid (ABA)-mediated drought tolerance in plants. However, it is unclear whether and to what extent protein farnesylation affects plant tolerance to high temperature conditions. The Arabidopsis heat-intolerant 5 (hit5) mutant was isolated because it was thermosensitive to prolonged heat incubation at 37 degrees C for 4 d but thermotolerant to sudden heat shock at 44 degrees C for 40 min. Map-based cloning revealed that HIT5 encodes the beta-subunit of the protein farnesyltransferase. hit5 was crossed with the aba-insensitive 3 (abi3) mutant, the aba-deficient 3 (aba3) mutant, and the heat shock protein 101 (hsp101) mutant, to characterize the HIT5-mediated heat stress response. hit5/abi3 and hit5/aba3 double mutants had the same temperature-dependent phenotypes as hit5. Additionally, exogenous supplementation of neither ABA nor the ABA synthesis inhibitor fluridone altered the temperature-dependent phenotypes of hit5. The hit5/hsp101 double mutant was still sensitive to prolonged heat incubation, yet its ability to tolerate sudden heat shock was lost. The results suggest that protein farnesylation either positively or negatively affects the ability of plants to survive heat stress, depending on the intensity and duration of high temperature exposure, in an ABA-independent manner. HSP101 is involved in the hit5-derived heat shock tolerance phenotype. PMID- 27673602 TI - Accelerated Approval Paths: What they do Mean and What they Should Not Mean? PMID- 27673603 TI - Clinically Guided Warfarin Dose Versus Genotyping In Early Achievement Of Stable Anticoagulant Effect Of Warfarin. PMID- 27673604 TI - The Analysis Of Lipid Modifying Agents Usage In Croatia During The Fifteen-Year Period. PMID- 27673605 TI - The Role Of Cyp2d6, Cyp3a4/5, And Abcb1 Polymorphisms In Patients Using Long Acting Injectable Risperidone. PMID- 27673606 TI - Food And Drug Interactions. PMID- 27673607 TI - Adherence To Pharmacological Treatment Of Chronic Non-Malignant Pain In Individuals Aged 65 and Older. PMID- 27673608 TI - Genetic and Non-Genetic Factors Affecting The Response To Clopidogrel Therapy. PMID- 27673609 TI - A Model For Managed Introduction Of New Medicines In Sweden. PMID- 27673610 TI - Rapid Health Technology Assessment Of New Medicines: Lessons From 15 Years Experience In Scotland. PMID- 27673611 TI - Pharmacoeconomics: How It Can Be Applied To Support Decisions In Health Care? PMID- 27673612 TI - Evaluation Of Medicines For Reimbursement By The National Social Insurance Institutions In Austria. PMID- 27673613 TI - Current Situation And Future Directions For Health Technology Assessment In Europe. PMID- 27673614 TI - How To Assess The Value Of The Drug? An Overview On Producing Economic Evidence In The R&D Process. PMID- 27673615 TI - Clinical Safety and Efficacy Issues Ariding in Relation to Alternative Formulations of nti Drugs Relevant to National Policy Development and Reimbursement Decisions - Focus on Calcineurin Inhibitors (cni). PMID- 27673616 TI - Cost Utility Analysis Of Selected Medical Equipment And Procedures In Croatia. PMID- 27673617 TI - Managing Increasing Expenses For Oncology Treatment In Lower Income Countries In Europe. PMID- 27673618 TI - Comparison Of Sorafenib Cost-Effectiveness And Budget Impact When Used For Advanced Hepatocellular Carcinoma In Two Neighbouring Balkan Countries. PMID- 27673619 TI - Health Technology Assessment (Hta) In Croatia: National And International View. PMID- 27673620 TI - Outlook For Biosimilar Molecules Entering Croatian Pharmaceutical Market In The Period From 2016 To 2020. PMID- 27673621 TI - Direct Medical Costs Of Treating Colorectal Cancer Patients With Different Chemotherapy Protocols Regarding Stage And Outcome Of The Disease. PMID- 27673622 TI - Pharmaceutical Pricing: How Much for The Risk Of Non-Cure? PMID- 27673623 TI - Decentralized Decision Making On Drug Reimbursement In A Middle-Income Country: Case Of Bosnia And Herzegovina. PMID- 27673624 TI - Why Abc/Ved Analysis In Oncology? The Experience Of A Major Russian Oncology Center. PMID- 27673625 TI - Excellence in Clinical Research: Clinical Trial Design. PMID- 27673626 TI - Implementation of Pharmacoeconomics to Support Pharmaceutical R&D Decisions Workshop. PMID- 27673627 TI - The Role of the National Competent Authority (NCA) In the Assessment of Medicinal Products in the National Procedure. PMID- 27673628 TI - New Methods and Designs of Clinical Trials. PMID- 27673629 TI - Efficacy of Antidepressants: Issues Related to Bias in Clinical Trials. PMID- 27673630 TI - Evaluation of Drugs in the Pediatric Population. PMID- 27673631 TI - Medicines for Pain and Palliative Care in Armenia. PMID- 27673632 TI - Availability of Information on use of Medicines in Children in Reference Books. PMID- 27673633 TI - Effects of Celastrol on Bv-2 Microglial Cells Exposed to in Vitro Hypoxia. PMID- 27673634 TI - Pregnancy Exposure to Drugs: Role of Clinical Pharmacologist. PMID- 27673635 TI - Effects of ABCB1 Genetic Polymorphism on the Oral Absorption of Losartan. PMID- 27673636 TI - Effects of Genetic Polymorphism of Cyp2c19 on the Pharmacokinetics of Zolpidem. PMID- 27673637 TI - Frequency of Potentially Dangerous Drug Combination Prescription in Elderly Patients with Cardiovascular Diseases. PMID- 27673639 TI - Integrating Pharmacovigilance and Pharmacogenomics: Croatian Experience. PMID- 27673638 TI - Drug-Drug Interaction of Paroxetine and Atomoxetine in Different CYP2D6 Genotypes. PMID- 27673640 TI - Patient with Multiple Drugs Intolerance: Oral Drug Provocation Test. PMID- 27673641 TI - The Role of Pharmacogenetic Testing in the Evaluation of Drug-Induced Liver Injury. PMID- 27673642 TI - The Modification of Anti-Inflammatory Properties of the Combined use of Nsaids and Glucosamine in Topical Dosage Form for Degenerative and Inflammatory Joint Diseases Treatment. PMID- 27673643 TI - Allele Frequency Distribution of CYP2C19 Genotypes Associated with Clopidogrel Resistance in Russian Population. PMID- 27673644 TI - Testing for Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) At the University Hospital Zagreb. PMID- 27673645 TI - Can Vascular Calcification be Associated with Warfarin Treatment? PMID- 27673646 TI - Adherence to Antiretroviral Therapy: Experience of Pharmaceutical Services of Maputo Central Hospital. PMID- 27673647 TI - The Use of Drugs for The Elderly With Community-Acquired Pneumonia. PMID- 27673648 TI - Following Guidelines and Prescribing Biological Medicine In A Situation of Reduced Budget. PMID- 27673649 TI - Availability and Affordability of Cardiovascular Medicines In Armenia. PMID- 27673650 TI - Outpatient Use of Antidepressants And The Incidence of Suicide In Montenegro 2000 2015: Are We Going In Optimistic Direction? PMID- 27673651 TI - Trend of Biosimilars Prescribing In A Croatian Teaching Hospital. PMID- 27673652 TI - Pharmacoeconomic Analysis of Antithrombotic Treatment In Coronary Artery Disease (Cad) Patients With Clopidogrel Hypersensitivity After Percutaneous Coronary Intervention (Pci). PMID- 27673653 TI - The Need For Medical Information In Relation To Diabetes Self-Management Among Emirati Women In United Arab Emirates. PMID- 27673654 TI - Anticoagulation For The Prevention of Stroke In Non-Vavular Af In General Practice: Room For Improvement. PMID- 27673655 TI - Antibiotic Use In Hospital Setting: Have Pharmacists An Active Role? PMID- 27673656 TI - Medicinal Product Regulation: Portugal's Framework. PMID- 27673657 TI - How to Promote Clinical Research in Cee? PMID- 27673658 TI - Current Challenges and Hurdles in New Drug Development. PMID- 27673659 TI - Use of Health Technology Assessment Agencies' Reports As Evidence For Making Decisions On Drug Reimbursement In Decentralized Decision-Making Environment. PMID- 27673660 TI - Can You Blindly Trust Decisions Made By Stringent Drug Regulatory Agencies? PMID- 27673661 TI - Sodium Selenate Restores Potassium Currents of Diabetic Cardiomyopathy: Rat Model Study. PMID- 27673662 TI - Why Reporting The Iodinated Contrast Media Used During Radiological Procedures Should Be Standard Practice: A Case Report. PMID- 27673663 TI - Neuroprotective And Memory-Enhancing Effects of The Water Extract From Pericarp of Mangosteen Fruit. PMID- 27673664 TI - Effect of Ondansetron On The Thermal Antinociceptive Effects of Procaine In The Rat Paw. PMID- 27673665 TI - Application of Physiologically Based Pharmacokinetic Modeling In Predicting Drug Drug Interactions For Sarpogrelate Hydrochloride In Humans. PMID- 27673666 TI - Standardization of In Vivo Drug Assessment Protocol For Testing Anti-Diabetic Plants: Effect And Possible Mechanism of Action of Fabaceae Beans. PMID- 27673667 TI - Inconsistency in Preclinical and Clinical Trials Exploring The Role of Hormone Replacement Therapy in Alzheimer's Disease. PMID- 27673668 TI - The Effects of SENS-111, A New H4R Antagonist, On Vertigo Induced by Caloric Test in Healthy Volunteers (HV) is Related to Plasma Concentrations. PMID- 27673669 TI - Are we Scared of Clinical Trials if not Sufficiently Informed and Educated? PMID- 27673670 TI - Attitudes to Performing Clinical Trials. PMID- 27673671 TI - Personalised Medicine Approaches For Identifying Effective Therapies. PMID- 27673672 TI - Clinical Pharmacology As A Key Principle Of Precision Medicine In Korea. PMID- 27673673 TI - Regulation Of Orphan Medicinal Products In Europe: History Trends And Challenges. PMID- 27673674 TI - The Role Of Pharmacogenetics In Individualized Treatment Choices. PMID- 27673676 TI - Safe Introduction of New Medicines Into Clinical Practice. PMID- 27673675 TI - Vascular Consequences Of Interruption Of Tnf-Inhibitor Therapy In Patients With Rheumatoid Arthritis. PMID- 27673677 TI - Effectiveness Assessment When Pharmacokinetics Makes A Difference, Macrolides And Azalide Example. PMID- 27673678 TI - New drugs for bad bugs: what's new and what's in the pipeline? PMID- 27673679 TI - Osteogrow Development: Bmp6 Bone Device For Enhancing Bone Healing. PMID- 27673680 TI - The Prevalence of Vitiligo: A Meta-Analysis. AB - OBJECTIVE: To conduct a meta-analysis assessing the prevalence of vitiligo. METHODS: Literatures that reported prevalence rates of vitiligo were identified using EMBASE, PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database and Weipu database for the period from inception to May 2016. We performed stratified analyses on possible sources of bias, including areas difference, years of publication, gender and age. Publication bias was assessed with Egger's test method. RESULTS: A total of 103 studies were eligible for inclusion. The pooled prevalence of vitiligo from 82 population- or community-based studies was 0.2% (95%CI: 0.1%-0.2%) and from 22 hospital-based studies was 1.8% (95%CI: 1.4%-2.1%). A relatively high prevalence of vitiligo was found in Africa area and in female patients. For population- or community-based studies, the prevalence has maintained at a low level in recent 20 years and it has increased with age gradually. For hospital-based studies, the prevalence has showed a decreased trend from 60s till now or from young to old. No significant publication bias existed in hospital-based studies (t = 0.47, P = 0.643), while a significant publication bias existed in population- or community based studies (t = 2.31, P = 0.026). CONCLUSION: A relatively high prevalence of vitiligo was found in Africa area and in female patients. The prevalence has maintained at a low level in recent years. It showed an inverse trend with age increment in population- or community-based studies and hospital-based studies. PMID- 27673681 TI - Acute Kidney Injury Treated with Dialysis outside the Intensive Care Unit: A Retrospective Observational Single-Center Study. AB - INTRODUCTION: The number of patients suffering from acute kidney injury requiring dialysis (AKI-D) is increasing. Whereas causes and outcome of AKI-D in the intensive care unit (ICU) are described extensively, few data exist about AKI-D patients treated outside the ICU. Aim of this study was to identify the causes of AKI-D, determine in-depth the comorbid conditions and outcome of this particular patient group and identify possibilities for its prevention. METHODS: We retrospectively studied all AKI-D patients treated outside the ICU in a single nephrology referral center between January 2010 and June 2015. Data on comorbid conditions, renal function and drug therapy prior to AKI-D, and possible causal events were collected. Patients were grouped into those with renal hypoperfusion as the predominant cause of AKI-D (hemodynamic group) and those with other causes (non-hemodynamic group). RESULTS: During 66 months 128 patients (57% male, mean age 69.3 years) were treated. AKI-D was community-acquired in 70.3%. The most frequent comorbidities were hypertension (62.5%), chronic kidney disease (CKD) (58.9%), coronary artery disease (CAD) (46.1%), diabetes (35.9%) and heart failure (34.1%). Most patients were prescribed diuretics (61.7%) and inhibitors of the renin-angiotensin-aldosterone system (RASI) (57.8%); 46.1% had a combination of both. In the 88 patients with hemodynamic AKI-D (68.8%) the most frequent initiating events were diarrhea (39.8%), infections (17.0%) and acute heart failure (13.6%). In the 40 patients with non-hemodynamic AKI-D (31.2%) interstitial nephritis (n = 15) was the prominent diagnosis. Patients with hemodynamic AKI-D were older (72.6 vs. 62.1 years, p = 0.001), suffered more often from CKD (68.2% vs. 33.3%, p = 0.003), CAD (54.5% vs. 27.5%, p = 0.004) and diabetes (42.0% vs. 22.5%, p = 0.033), and were more frequently on diuretics (75.0% vs. 32.5%, p<0.001), RASI (67.0% vs. 37.5%, p = 0.002) or their combination (58.0% vs. 20.0%, p<0.001). Twenty-two (17.2%) patients died and 27 (21.1%) patients died or developed end-stage renal disease. CONCLUSION: AKI-D treated outside the ICU is most often caused by renal hypoperfusion. It predominantly afflicts elderly patients with one or more comorbid conditions, who are treated with diuretics and RASI and have an acute illness leading to volume depletion. Early discontinuation of these drugs may be a successful strategy to avoid AKI-D in vulnerable patients. PMID- 27673682 TI - Data-Driven Metabolic Pathway Compositions Enhance Cancer Survival Prediction. AB - Altered cellular metabolism is an important characteristic and driver of cancer. Surprisingly, however, we find here that aggregating individual gene expression using canonical metabolic pathways fails to enhance the classification of noncancerous vs. cancerous tissues and the prediction of cancer patient survival. This supports the notion that metabolic alterations in cancer rewire cellular metabolism through unconventional pathways. Here we present MCF (Metabolic classifier and feature generator), which incorporates gene expression measurements into a human metabolic network to infer new cancer-mediated pathway compositions that enhance cancer vs. adjacent noncancerous tissue classification across five different cancer types. MCF outperforms standard classifiers based on individual gene expression and on canonical human curated metabolic pathways. It successfully builds robust classifiers integrating different datasets of the same cancer type. Reassuringly, the MCF pathways identified lead to metabolites known to be associated with the pertaining specific cancer types. Aggregating gene expression through MCF pathways leads to markedly better predictions of breast cancer patients' survival in an independent cohort than using the canonical human metabolic pathways (C-index = 0.69 vs. 0.52, respectively). Notably, the survival predictive power of individual MCF pathways strongly correlates with their power in predicting cancer vs. noncancerous samples. The more predictive composite pathways identified via MCF are hence more likely to capture key metabolic alterations occurring in cancer than the canonical pathways characterizing healthy human metabolism. PMID- 27673683 TI - A Sensitivity Analysis of the Impact of Rain on Regional and Global Sea-Air Fluxes of CO2. AB - The global oceans are considered a major sink of atmospheric carbon dioxide (CO2). Rain is known to alter the physical and chemical conditions at the sea surface, and thus influence the transfer of CO2 between the ocean and atmosphere. It can influence gas exchange through enhanced gas transfer velocity, the direct export of carbon from the atmosphere to the ocean, by altering the sea skin temperature, and through surface layer dilution. However, to date, very few studies quantifying these effects on global net sea-air fluxes exist. Here, we include terms for the enhanced gas transfer velocity and the direct export of carbon in calculations of the global net sea-air fluxes, using a 7-year time series of monthly global climate quality satellite remote sensing observations, model and in-situ data. The use of a non-linear relationship between the effects of rain and wind significantly reduces the estimated impact of rain-induced surface turbulence on the rate of sea-air gas transfer, when compared to a linear relationship. Nevertheless, globally, the rain enhanced gas transfer and rain induced direct export increase the estimated annual oceanic integrated net sink of CO2 by up to 6%. Regionally, the variations can be larger, with rain increasing the estimated annual net sink in the Pacific Ocean by up to 15% and altering monthly net flux by > +/- 50%. Based on these analyses, the impacts of rain should be included in the uncertainty analysis of studies that estimate net sea-air fluxes of CO2 as the rain can have a considerable impact, dependent upon the region and timescale. PMID- 27673685 TI - Theory and Experiment of Binary Diffusion Coefficient of n-Alkanes in Dilute Gases. AB - Binary diffusion coefficients were measured for n-pentane, n-hexane, and n-octane in helium and of n-pentane in nitrogen over the temperature range of 300 to 600 K, using reversed-flow gas chromatography. A generalized, analytical theory is proposed for the binary diffusion coefficients of long-chain molecules in simple diluent gases, taking advantage of a recently developed gas-kinetic theory of the transport properties of nanoslender bodies in dilute free-molecular flows. The theory addresses the long-standing question about the applicability of the Chapman-Enskog theory in describing the transport properties of nonspherical molecular structures, or equivalently, the use of isotropic potentials of interaction for a roughly cylindrical molecular structure such as large normal alkanes. An approximate potential energy function is proposed for the intermolecular interaction of long-chain n-alkane with typical bath gases. Using this potential and the analytical theory for nanoslender bodies, we show that the diffusion coefficients of n-alkanes in typical bath gases can be treated by the resulting analytical model accurately, especially for compounds larger than n butane. PMID- 27673686 TI - Extended Intermolecular Interactions Governing Photocurrent-Voltage Relations in Ternary Organic Solar Cells. AB - Efficient organic solar cells are based on (electron) donor-acceptor heterojunctions. An optically generated excited molecular state (exciton) is dissociated at this junction, forming a charge-transfer (CT) state in an intermediate step before the electron and hole are completely separated. The observed highly efficient dissociation of this Coulombically bound state raises the question on the dissociation mechanism. Here, we show that the observed high quantum yields of charge carrier generation and CT state dissociation are due to extended (and consequently weakly bound) CT states visible in absorption and emission spectra and first-principles calculations. Identifying a new geminate pair loss mechanism via donor excimers, we find that the hole on the small molecule donor is not localized on a single molecule and charge separation is correlated with the energetic offset between excimer and CT states. Thus, the charges upon interface charge transfer and even in the case of back-transfer and recombination are less localized than commonly assumed. PMID- 27673684 TI - The Association of Hydration Status with Physical Signs, Symptoms and Survival in Advanced Cancer-The Use of Bioelectrical Impedance Vector Analysis (BIVA) Technology to Evaluate Fluid Volume in Palliative Care: An Observational Study. AB - BACKGROUND: Hydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer to examine the association of fluid status with symptoms, physical signs, renal biochemical measures and survival. MATERIALS AND METHODS: An observational study of 90 adults with advanced cancer receiving care in a UK specialist palliative care inpatient unit was conducted. Hydration status was assessed using BIVA in addition to assessments of symptoms, physical signs, performance status, renal biochemical measures, oral fluid intake and medications. The association of clinical variables with hydration was evaluated using regression analysis. A survival analysis was conducted to examine the influence of hydration status and renal failure. RESULTS: The hydration status of participants was normal in 43 (47.8%), 'more hydrated' in 37 (41.1%) and 'less hydrated' in 10 (11.1%). Lower hydration was associated with increased symptom intensity (Beta = -0.29, p = 0.04) and higher scores for physical signs associated with dehydration (Beta = 10.94, p = 0.02). Higher hydration was associated with oedema (Beta = 2.55, p<0.001). Median survival was statistically significantly shorter in 'less hydrated' patients (44 vs. 68 days; p = 0.049) and in pre-renal failure (44 vs. 100 days; p = 0.003). CONCLUSIONS: In advanced cancer, hydration status was associated with clinical signs and symptoms. Hydration status and pre-renal failure were independent predictors of survival. Further studies can establish the utility of BIVA as a standardised hydration assessment tool and explore its potential research application, in order to inform the clinical management of fluid balance in patients with advanced cancer. PMID- 27673687 TI - Highly Conductive Graphene and Polyelectrolyte Multilayer Thin Films Produced From Aqueous Suspension. AB - Rapid, large-scale exfoliation of graphene in water has expanded its potential for use outside niche applications. This work focuses on utilizing aqueous graphene dispersions to form thin films using layer-by-layer processing, which is an effective method to produce large-area coatings from water-based solutions of polyelectrolytes. When layered with polyethyleneimine, graphene flakes stabilized with cholate are shown to be capable of producing films thinner than 100 nm. High surface coverage of graphene flakes results in electrical conductivity up to 5500 S m-1 . With the relative ease of processing, the safe, cost effective nature of the ingredients, and the scalability of the deposition method, this system should be industrially attractive for producing thin conductive films for a variety of electronic and antistatic applications. PMID- 27673688 TI - Suppressive Effect of Carvedilol on Na+/Ca2+ Exchange Current in Isolated Guinea Pig Cardiac Ventricular Myocytes. AB - BACKGROUND AND AIMS: Carvedilol ((+/-)-1-(carbazol-4-yloxy)-3-[[2-(o methoxyphenoxy)ethyl]amino]-2-propanol), a beta-adrenoceptor-blocker, has multi channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na+/Ca2+ exchanger (NCX1) has not been investigated. METHODS AND RESULTS: We examined the effects of carvedilol and metoprolol, 2 beta-blockers, on Na+/Ca2+ exchange current (INCX) in guinea-pig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1. Carvedilol suppressed INCX in a concentration-dependent manner but metoprolol did not. IC50 values for the Ca2+ influx (outward) and efflux (inward) components of INCX were 69.7 and 61.5 umol/l, respectively. Carvedilol at 100 MUmol/l inhibited INCX in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 umol/l abolished ouabain-induced delayed afterdepolarizations. CONCLUSION: Carvedilol inhibited cardiac NCX in a concentration-dependent manner in isolated cardiac ventricles, but metoprolol did not. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations. PMID- 27673689 TI - A Multi-Institutional Feasibility Study on the Use of Automated Screening Systems for Quality Control Rescreening of Cervical Cytology. AB - OBJECTIVE: To evaluate the efficacy of the automated screening system FocalPoint for cervical cytology quality control (QC) rescreening. False-negative rates (FNRs) were evaluated by a multi-institutional retrospective study. STUDY DESIGN: Cervical cytology slides that had already been reported as negative for intraepithelial lesion or malignancy (NILM) were chosen arbitrarily for FocalPoint rescreening. Slides stratified into the highest 15% probability of being abnormal were rescreened by a cytotechnologist. The slides that were abnormal were reevaluated by a cytopathologist to be false negatives. RESULTS: Rescreening of 12,000 slides, i.e. 9,000 conventional slides and 3,000 liquid based cytology (LBC) slides, was performed; 9,826 (7,393 conventional and 2,433 LBC) were satisfactory for FocalPoint (2,174 were determined unsatisfactory) and those within the highest 15% of probability (1,496, i.e. 1,123 conventional and 373 LBC) were rescreened. As a result, 117 (96 conventional and 21 LBC) were determined as abnormal (other than NILM) and the FNR was 1.19%. Among these 117 slides, 40 (35 conventional and 5 LBC) were determined as high-grade squamous intraepithelial lesion and greater (HSIL+). CONCLUSION: Of 117 (1.19%) abnormal slides detected, 40 (0.41%) were determined to be HSIL+. This result suggests that FocalPoint is effective for QC rescreening of cervical cytology. PMID- 27673690 TI - Hyperglycemia and Advanced Glycation End Products Regulate miR-126 Expression in Endothelial Progenitor Cells. AB - BACKGROUND/AIMS: Dysfunction of endothelial progenitor cell (EPCs) contributes to diabetic vascular disease. We reported that downregulated miR-126 in diabetic patients causes EPC dysfunction. The study was designed to investigate how high glucose (HG) and advanced glycation end products (AGEs) regulate miR-126 expression and whether miR-126 mediates the effects of HG and AGEs on EPCs. METHODS: We first tested the effects of glucose (5.5-50 mM) and AGEs at 50-200 mg/l on EPC proliferation and selected HG at 50 mM and AGEs at 50 mg/l for further experiments. EPCs were stimulated with HG and AGEs, and miR-126 expression was measured by real-time PCR. Reactive oxygen species (ROS) were measured by immunofluorescence microscopy and flow cytometry. IL-6 and TNF-alpha levels in EPC supernatants were determined by ELISA. The effects of miR-126 on ROS and inflammatory markers under stimulation of HG and AGEs were also assessed. Finally, the effects of inhibitors of PI3K and Akt on AGE-mediated miR-126 expression were examined. RESULTS: HG and AGEs increased IL-6, TNF-alpha and ROS and decreased miR-126 expression in EPCs. miR-126 negatively regulated IL-6, TNF alpha and ROS. miR-126 overexpression reduced and miR-126 inhibition further increased the inflammatory markers and ROS induced by HG and AGEs. Inhibitors of PI3K and Akt further decreased miR-126 expression in the presence of AGEs. CONCLUSIONS: In conclusion, hyperglycemia and AGEs decrease miR-126 expression in EPCs. Recovering miR-126 expression may protect EPCs against dysfunction induced by HG and AGEs. PMID- 27673691 TI - Restoration of ventricular septal hypoperfusion by cardiac resynchronization therapy in patients with permanent right ventricular pacing. AB - BACKGROUND: Pacing from the right ventricular apex (RVA) is associated with cardiac dysfunction and shows electrophysiological features similar to left bundle branch block in which left ventricular (LV) mechanical dyssynchrony impairs septal coronary artery perfusion. METHODS: A total of 62 non-ischemic patients with an implanted pacemaker at the RVA with a pacing rate of >95% were studied. LV septal coronary perfusion as indicated by the LV septal perfusion index was measured by electrocardiography (ECG)-gated single-photon emission computed tomography for all patients at baseline and for patients who were upgraded to CRT at 6months after CRT. Relationships among LV septal perfusion index, QRS duration, and LV ejection fraction were analyzed. RESULTS: Among the patients with permanent RVA pacing, 28 of 62 (45%) had impaired septal perfusion (i.e., septal perfusion index <0.9). The LV septal perfusion index was significantly correlated with both QRS duration (r=-0.763, p<0.001) and LV ejection fraction (r=0.462, p=0.001). Eleven patients were upgraded to CRT. CRT significantly improved the LV septal perfusion index from 0.63 (SD=0.13) to 0.89 (SD=0.19) (p<0.001)and cardiac function: LV end-systolic volume from 102.3mL (SD=70.0) to 179.7mL (SD=118.4) (p=0.002) and LV ejection fraction from 22.5 (SD=8.9%) to 38.4% (SD=13.9%) (p=0.001). CONCLUSIONS: Nearly half of the non ischemic patients with permanent RVA pacing presenting with prolonged QRS duration and LV dysfunction developed LV septal hypoperfusion. Both septal perfusion and LV function improved in patients who were upgraded to CRT. PMID- 27673692 TI - The relationship between post-operative time and cardiac autonomic modulation in breast cancer survivors. AB - BACKGROUND/OBJECTIVES: Breast cancer survivors present autonomic dysfunction when evaluated by their heart rate variability (HRV). The purpose of this study is to investigate the relationship between post-operative time and cardiac autonomic modulation in breast cancer survivors and compare these values to those of women without cancer. METHODS: This is a cross-sectional study consisting of 45 women from 35 to 70years old. These women were divided into two after breast cancer groups (BCG1 and BCG2) and a control group (CG). Group BCG1 consisted of women who had undergone breast cancer surgery within the last 18months and BCG2 those whose postoperative periods were more than 18months. The control group was formed by cancer-free women. HRV indices were used in the time and the frequency domain and geometric indexes. RESULTS: The indices in millisecond, RMSSD (BCG1=19.83; BCG2=14.99; CG=31.46), SD1 (BCG1=14.03; BCG2=10.61; CG=22.27), SD2 (BCG1=39.17; BCG2=35.28; CG=61.16), SDNN (BCG1=29.58; BCG2=26.12; CG=46.36) and HF in milliseconds squared (BCG1=194.2; BCG2=91.07; CG=449.4) showed statistically significant reductions in the breast cancer groups compared to the CG (p<=0.0001). Lower SD1 index values were observed when comparing BCG2 to BCG1. CONCLUSIONS: Breast cancer survivors regardless of their postoperative period exhibited a decrease in overall variability and both sympathetic and parasympathetic activity when compared to women without the disease. The group with the longer postoperative period manifested more pronounced autonomic modulation changes. PMID- 27673693 TI - Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives. AB - Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies. PMID- 27673694 TI - Brain resting state functional magnetic resonance imaging in patients with takotsubo cardiomyopathy an inseparable pair of brain and heart. AB - BACKGROUND: Takotsubo cardiomyopathy (TTC) is often triggered by emotional or physical stress factors. Psychological variables can have an impact on the physical manifestations of heart disease. TTC may reflect stunned myocardium from a neurogenic source. Anatomical connections between different parts of the brain can be visualized by diffusion tensor imaging (DTI) and thus, expressed by diffusion coefficient - fractional anisotropy (FA). A novel tool used to evaluate brain function in the absence of task is resting state functional magnetic resonance imaging (RS-fMRI). METHODS: The study included both psychological tests and RS-fMRI examination, and was performed uniformly, in patients with takotsubo and healthy controls. The final group of patients consisted of 13 women, each who underwent a typical pattern of TTC triggered by emotionally stressful factors. The control group included thirteen healthy, age-matched women. RESULTS: Psychological tests revealed that the Type D personality was not more likely to appear among studied patients with takotsubo cardiomyopathy than amongst the healthy population. However, the level of anxiety seen in patients with TTC was increased. There were no differences in FA values between patients and healthy controls. RS-fMRI showed that TTC patients had increased connectivity areas in the precuneus. The healthy controls, when compared to TTC patients had increased connectivity in the ventromedial prefrontal cortex. CONCLUSIONS: Taking into account the RS-fMRI results, psychological testing may suggest that TTC patients place a greater focus on themselves (increased tendency to experience negative affectivity, greater conscientiousness) and might have problems with emotional control. Our findings lead to the hypothesis that there is a personality profile for TTC patients' reactions to stressful triggers. PMID- 27673695 TI - Transcatheter aortic valve implantation versus surgical aortic valve replacement: A meta-analysis of randomized controlled trials. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become a widely utilized method of treatment of severe aortic valve stenosis. The present meta analysis included all published relevant randomized controlled trials (RCTs) and aimed to compare the safety and efficacy of TAVI compared to surgical aortic valve replacement (AVR). METHOD: Nine electronic databases were comprehensively searched. Eligible studies were required to be randomized controlled trials which reported comparative endpoints on both TAVI and AVR. RESULTS: Five published RCTs were included in the meta-analysis. A total of 3828 patients were studied. The overall mortality and stroke rates at 30days and 1year were not significantly different between TAVI and AVR. Patients undergoing TAVI were more likely to experience vascular complications, aortic regurgitation and permanent pacemaker insertion, however, they were less likely to encounter acute renal failure and major haemorrhage. CONCLUSIONS: The data suggest that TAVI is a safe and efficacious alternative to surgical aortic valve replacement in judiciously selected patients. PMID- 27673696 TI - STEM/EELS Imaging of Magnetic Hybridization in Symmetric and Symmetry-Broken Plasmon Oligomer Dimers and All-Magnetic Fano Interference. AB - Negative-index metamaterials composed of magnetic plasmon oligomers are actively being investigated for their potential role in optical cloaking, superlensing, and nanolithography applications. A significant improvement to their practicality lies in the ability to function at multiple distinct wavelengths in the visible part of spectrum. Here we utilize the nanometer spatial-resolving power of electron energy-loss spectroscopy to conclusively demonstrate hybridization of magnetic plasmons in oligomer dimers that can achieve this goal. We also show that breaking the dimer's symmetry can induce all-magnetic Fano interferences based solely on the interplay of bright and dark magnetic modes, allowing us to further tailor the system's optical responses. These features are engineered through the design of the oligomer's underlying nanoparticle elements as elongated Ag nanodisks with spectrally isolated long-axis plasmon resonances. The resulting magnetic plasmon oligomers and their hybridized assemblies establish a new design paradigm for optical metamaterials with rich functionality. PMID- 27673697 TI - Simultaneous quantitation of 14 active components in Yinchenhao decoction by using ultra high performance liquid chromatography with diode array detection: Method development and ingredient analysis of different commonly prepared samples. AB - We developed a novel quantitative analysis method based on ultra high performance liquid chromatography coupled with diode array detection for the simultaneous determination of the 14 main active components in Yinchenhao decoction. All components were separated on an Agilent SB-C18 column by using a gradient solvent system of acetonitrile/0.1% phosphoric acid solution at a flow rate of 0.4 mL/min for 35 min. Subsequently, linearity, precision, repeatability, and accuracy tests were implemented to validate the method. Furthermore, the method has been applied for compositional difference analysis of 14 components in eight normal-extraction Yinchenhao decoction samples, accompanied by hierarchical clustering analysis and similarity analysis. The result that all samples were divided into three groups based on different contents of components demonstrated that extraction methods of decocting, refluxing, ultrasonication and extraction solvents of water or ethanol affected component differentiation, and should be related to its clinical applications. The results also indicated that the sample prepared by patients in the family by using water extraction employing a casserole was almost same to that prepared using a stainless-steel kettle, which is mostly used in pharmaceutical factories. This research would help patients to select the best and most convenient method for preparing Yinchenhao decoction. PMID- 27673699 TI - Static Adsorption of an Ethoxylated Nonionic Surfactant on Carbonate Minerals. AB - The static adsorption of C12-14E22, which is a highly ethoxylated nonionic surfactant, was studied on different minerals using high-performance liquid chromatography (HPLC) combined with an evaporative light scattering detector (ELSD). Of particular interest is the surfactant adsorption in the presence of CO2 because it can be used for foam flooding in enhanced oil recovery applications. The effects of the mineral type, impurities, salinity, and temperature were investigated. The adsorption of C12-14E22 on pure calcite was as low as 0.01 mg/m2 but higher on dolomite depending on the silica and clay content in the mineral. The adsorption remained unchanged when the experiments were performed using a brine solution or 0.101 MPa (1 atm) CO2, which indicates that electrostatic force is not the governing factor that drives the adsorption. The adsorption of C12-14E22 on silica may be due to hydrogen bonding between the oxygen in the ethoxy groups of the surfactant and the hydroxyl groups on the mineral surface. Additionally, thermal decomposition of the surfactant was severe at 80 degrees C but can be inhibited by operating in a reducing environment. Under reducing conditions, adsorption of C12-14E22 increased at higher temperatures. PMID- 27673700 TI - Correction to Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives. PMID- 27673698 TI - Atrial fibrillation is associated with an increased risk of myocardial infarction: Insights from a meta-analysis. AB - BACKGROUND AND AIMS: The presence of atrial fibrillation (AF) markedly increases the risk of stroke and mortality in patients. Whether AF is a risk factor for myocardial infarction (MI) is discrepant from current studies. The aim of this meta-analysis was to ascertain the association of AF with incident MI. METHODS: Studies were identified through PubMed, CENTRAL, EMBASE, reviews and reference lists of relevant papers. Results of the MI outcome were presented as hazard ratio (HR) and 95% confidence interval (CI). Statistical analyses were performed with Stata 12.0 (Stata Corp LP, College Station, Texas, USA). RESULTS: Twelve studies, with a total of 169,306 patients, were included in the analysis. AF was associated with a 47% increased risk of MI (HR:1.47; 95% CI: 1.21-1.80; p = 0.000; I2 = 84.1%), while in patients free of coronary heart disease at baseline the risk could be increased by 71% (HR:1.71; 95% CI: 1.36-2.14; p = 0.000; I2 = 83.1%). Moreover, patients with AF had higher MI risk in the studies with lower mean age (<60 years) (HR:1.66; 95% CI: 1.26-2.20; p = 0.000; I2 = 82.9%) than in the studies with higher mean age (>=60 years) (HR:1.35; 95% CI: 1.00-1.82; p = 0.000; I2 = 84.9%). Sex difference also existed, and the association between AF and MI was stronger in women (HR:2.02; 95% CI: 1.60-2.56; p = 0.017; I2 = 61.0%) than in men (HR:1.44; 95% CI: 1.13-1.84; p = 0.000; I2 = 76.1%). CONCLUSIONS: AF is associated with an increased risk of incident MI, especially in patients free of coronary heart disease at baseline, young patients and women. The findings need confirmation in well-designed observational trials. PMID- 27673701 TI - Ti(OiPr)4-Mediated Multicomponent Reactions Involving Triple Additions to Isonitrile Carbon Atoms. AB - Double addition of Grignard reagents to isonitriles was achieved in the presence of stoichiometric amounts of [Ti(OiPr)4]. Functionalized isonitrile components were obtained in situ via lithiation of chiral and achiral 2-oxazolines, and the resulting amidomethyltitanium intermediate further reacted with a range of electrophiles. The established multicomponent procedure gave rise to highly substituted 2-aminomorpholines, acyclic diamino alcohols, and prenylated amino alcohols via straightforward synthetic protocols. PMID- 27673703 TI - Nucleation and Conformality of Iridium and Iridium Oxide Thin Films Grown by Atomic Layer Deposition. AB - Nucleation and conformality are important issues, when depositing thin films for demanding applications. In this study, iridium and iridium dioxide (IrO2) films were deposited by atomic layer deposition (ALD), using five different processes. Different reactants, namely, O2, air, consecutive O2 and H2 (O2 + H2), and consecutive O3 and H2 (O3 + H2) pulses were used with iridium acetylacetonate [Ir(acac)3] to deposit Ir, while IrO2 was deposited using Ir(acac)3 and O3. Nucleation was studied using a combination of methods for film thickness and morphology evaluation. In conformality studies, microscopic lateral high-aspect ratio (LHAR) test structures, specifically designed for accurate and versatile conformality testing of ALD films, were used. The order of nucleation, from the fastest to the slowest, was O2 + H2 > air ~ O2 > O3 > O3 + H2, whereas the order of conformality, from the best to the worst, was O3 + H2 > O2 + H2 > O2 > O3. In the O3 process, a change in film composition from IrO2 to metallic Ir was seen inside the LHAR structures. Compared to the previous reports on ALD of platinum group metals, most of the studied processes showed good to excellent results. PMID- 27673705 TI - Demethyleugenol beta-Glucopyranoside Isolated from Agastache rugosa Decreases Melanin Synthesis via Down-regulation of MITF and SOX9. AB - Agastache rugosa (Fisch. & C. A. Mey.) Kuntze has been well-known for its antioxidative properties. This study investigated the anti-melanogenesis effect of demethyleugenol beta-d-glucopyranoside (1) from A. rugosa by studying molecular regulation of melanogenesis in melan-a mouse melanocytes and normal human epidermal melanocytes (NHEMs) and in in vivo models. The SRY (sex determining region on the Y chromosome)-related high-mobility group (HMG) box 9 (SOX9), one of the critical factors that affect skin pigmentation, is up regulated. Interestingly, 1 down-regulated the expression of SOX9 and microphthalmia-associated transcription factor (MITF). Reduction of these two transcription factors resulted in a decrease in melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase. As a result, 1 significantly inhibited melanin synthesis in melan-a mouse melanocytes and NHEMs. In addition, the anti-melanogenic effect of 1 was confirmed in zebrafish and reconstructed skin tissue models. In conclusion, 1, as a potent SOX9 regulator, ameliorates skin pigmentation. PMID- 27673704 TI - Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder. AB - Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. PMID- 27673707 TI - Imitations and Transformations: On Side Effects of the ADHD Epidemic. AB - The attention deficit hyperactivity disorder epidemic has been the subject of much scrutiny, especially in relation to the medicalization of children, and, to a lesser degree, to the use of Ritalin as a performance enhancer or party drug (e.g., Keane 2008; Whitaker 2010; Bowden 2013). In this article, my focus is on non-investigated side effects of this epidemic, namely the use of (prescription) Ritalin among heavy drug users. Based on fieldwork conducted in one of the largest cities in Denmark, in this article I trace the spread of intravenous use of Ritalin, and examine how different ways of ingesting Ritalin transform the drug itself, and, with this, transform treatment practices, parts of the drug scene, and the bodies of users. In my analysis, I draw on insights from anthropological theories on imitation and from material semiotics. PMID- 27673706 TI - Perfectionism, emotion dysregulation, and affective disturbance in relation to clinical impairment in college-age women at high risk for or with eating disorders. AB - Individuals with eating disorders (EDs) demonstrate impaired quality of life; however, less than one-third report severe clinical impairment. Thus, it is important to determine factors that may identify those who are most likely to report marked impairment. Perfectionism, emotion dysregulation, and aspects of affective disturbance, such as anxiety and depression, are independently associated with eating pathology and clinical impairment in eating and other disorders. However, little research has explored these three factors concurrently in relation to eating pathology. It is possible that the combined interaction effect of these constructs could be especially harmful. The current study examined the influence of these constructs and their interactions on clinical impairment in college-aged women at high risk for or with a DSM-5 clinical or subclinical ED. Although the three-way interaction of perfectionism, emotion dysregulation, and affective disturbance (i.e., anxiety or depression) was not significant, the two-way interaction between perfectionism and emotion dysregulation was significant such that those who were high in both perfectionism and emotion dysregulation reported the highest levels of clinical impairment. This suggests that the combination of perfectionism and emotion dysregulation may be especially problematic for those with or at high risk for EDs. Interestingly, perfectionism alone was not a predictor of clinical impairment when accounting for the other constructs, implying that perfectionism may have a greater impact when in conjunction with emotion dysregulation. Understanding the impact of combined perfectionistic tendencies and emotion dysregulation on clinical impairment may better inform treatment and more directly target contributors to impaired quality of life. PMID- 27673708 TI - Consideration of Personal Adverse Childhood Experiences during Implementation of Trauma-Informed Care Curriculum in Graduate Health Programs. AB - CONTEXT: Scientific findings of adverse childhood experiences (ACEs) and their lifelong graded relationship with leading causes of death are well established. Many health care practitioners, however, have yet to implement ACEs screening in clinical practice. Furthermore, ACEs screening and trauma-informed care (TIC) are not part of standard graduate-level training. OBJECTIVE: To 1) implement trauma informed curriculum for multiple graduate health programs, 2) determine student understanding of and willingness to address ACEs, and 3) assess the relationship between students voluntarily evaluating their individual ACE Score and their attitude toward ACEs and TIC. DESIGN: Prospective study with pre- and postcurricular surveys (12-question digital survey administered before and after the curriculum) for 967 graduate students from 9 health professions programs at 2 campuses who received curriculum focused on ACEs and TIC. MAIN OUTCOME MEASURES: Students' understanding of ACEs and TIC, their awareness of personal ACEs, and their willingness to incorporate TIC in practice. RESULTS: Among students who voluntarily completed an ACE questionnaire, there was statistical significance in familiarity with clinical and scientific findings of the ACE Study (p < 0.001) and familiarity with TIC (p < 0.02). A significant intercampus difference in the students' familiarity with the scientific and clinical findings of the ACE Study (p < 0.05) was found. CONCLUSION: Students and future health care practitioners who voluntarily assess their ACE Score are significantly more likely to understand scientific and clinical findings of the ACE Study as well as TIC. PMID- 27673709 TI - Family Impact and Infant Emotional Outcomes Following Diagnosis of Serious Liver Disease or Transplantation in Infancy. AB - OBJECTIVES: Research is lacking into the emotional effects on families of serious chronic illness in infants. We examined the effect of the diagnosis of serious liver disease in infants upon parent psychological symptoms and family functioning. We hypothesized that parent psychological symptoms, family functioning, and father engagement will predict infant emotional outcomes. METHODS: Parents of infants recently diagnosed with serious liver disease completed validated questionnaires about parent stress, family function, impact of the illness on the family, and father engagement. The measures were repeated after 1 year, with the addition of the Child Behavior Checklist (CBCL). RESULTS: Parents of 37 infants participated. Parent stress and family functioning scores were not elevated. Parent psychological symptoms, family function, and father engagement did not predict infant outcome. For mothers, infant diagnosis other than biliary atresia, number of outpatient visits, and impact of the illness on the family explained 32% of the variation in CBCL (P = 0.001). For fathers, socioeconomic status, infant diagnosis other than biliary atresia, whether the infant had had a transplant, and impact of the illness on the family explained 44% of the variation in CBCL (P < 0.001). CONCLUSIONS: Parents and families appear to be resilient in coping with serious infant illness. Infant diagnosis other than biliary atresia and parental perceptions of high impact of the illness on the family are indicators of negative emotional outcomes for infants with serious liver disease. Psychosocial interventions for infants with chronic illness should target reducing the impact of illness on the family. PMID- 27673710 TI - The Etiology and Clinical Course of Chronic Pancreatitis in Children With Early Onset of the Disease. AB - OBJECTIVES: The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP. METHODS: A total of 276 children with CP, hospitalized from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings, and treatment were reviewed. Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR). RESULTS: The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs 3.00; P < 0.05) and underwent surgeries more frequently (25.5% vs 8.9%; P < 0.05). It could be associated with significantly longer follow-up in early onset group (median 6 vs 4 years; P < 0.05). There were no differences in nutritional status or exocrine and endocrine pancreatic function. CONCLUSIONS: Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries. PMID- 27673712 TI - How much of a problem is resistance in treating hepatitis C? AB - PURPOSE OF REVIEW: Directly acting antiviral drug (DAA) treatments represent a major advance in hepatitis C management, achieving virological cures in excess of 90%. When treatment failure occurs, it is mostly due to relapse with the emergence of resistance-associated variants. RECENT FINDINGS: Data from in-vitro studies and clinical trials have enabled characterization of the amino acid substitutions in antiviral drug targets that confer reduced susceptibility to DAAs. These resistance-associated substitutions (RASs) may exist prior to treatment, and are associated with, but do not inevitably result in, treatment failure. The most important RASs with current regimens occur in the NS5A protein of viral variants, which may persist for years after treatment. The optimal strategy is to prevent resistance through administering the best treatment, appropriately matched to patient and virological characteristics, for example the presence of cirrhosis, prior exposure to interferon and so on. SUMMARY: International treatment guidelines have been developed to select treatments, which may vary in duration and coadministration with ribavirin. Routine resistance testing prior to treatment of naive patients is not generally recommended. Next-generation DAAs will further reduce the emergence of RASs and, because of activity against RASs to currently used DAAs, will be used as rescue therapies for patients who have failed treatment. PMID- 27673716 TI - Intraoperative 4-Dimensional Microscope-Integrated Optical Coherence Tomography Guided 27-Gauge Transvitreal Choroidal Biopsy for Choroidal Melanoma. PMID- 27673715 TI - INFECTIOUS ENDOPHTHALMITIS AFTER GLAUCOMA DRAINAGE IMPLANT SURGERY: Clinical Features, Microbial Spectrum, and Outcomes. AB - PURPOSE: To report the clinical features, microbial spectrum, and treatment outcomes of endophthalmitis after glaucoma drainage implant (GDI) surgery. METHODS: Records of patients diagnosed with endophthalmitis after GDI surgery were reviewed. Data on clinical course, microbiological laboratory results, and treatment were analyzed. RESULTS: Of 1,891 eyes that underwent GDI surgery, 14 eyes (0.7%) developed endophthalmitis. The mean time interval between GDI surgery and diagnosis of endophthalmitis was 2.6 +/- 3.2 years (median, 1.3 years; range, 11 days-11.4 years). For initial treatment, 13/14 eyes underwent vitreous tap and injection of intravitreal antibiotics and 1/14 eyes underwent primary pars plana vitrectomy. Three additional eyes underwent pars plana vitrectomy because of deteriorating clinical course. Glaucoma drainage implant erosion was present in 9/14 eyes. All 9 eroded GDIs were surgically removed within a mean of 9 +/- 5 days (range 2-29 days) after diagnosis of endophthalmitis. Overall, mean logarithm of the minimum angle of resolution best-corrected visual acuity worsened from 0.7 +/- 0.7 (Snellen equivalent 20/100) at baseline to 1.6 +/- 1.1 (Snellen equivalent 20/800) at final follow-up (P = 0.005). Mean duration between the onset of symptoms and presentation was significantly longer in patients with decreased final best-corrected visual acuity (>2 Snellen lines) compared to patients with stable final best-corrected visual acuity (6.8 vs. 1.0 days; P = 0.005). CONCLUSION: Glaucoma drainage implant-related endophthalmitis is rare and often associated with GDI erosion. Patients who presented earlier after the onset of symptoms had better final visual outcomes. Prompt evaluation and treatment is required, often with removal of the eroded GDI. PMID- 27673714 TI - In Vivo Cellular Infiltration and Remodeling in a Decellularized Ovine Osteochondral Allograft. AB - Interest in decellularized tissues has steadily gained as potential solutions for degenerative diseases and traumatic events, replacing sites of missing tissue, and providing the relevant biochemistry and microstructure for tissue ingrowth and regeneration. Osteoarthritis, a progressive and debilitating disease, is often initiated with the formation of a focal defect in the otherwise smooth surface of articular cartilage. Decellularized cartilage tissue, which maintains the structural complexity of the native extracellular matrix, has the potential to provide a clinically relevant solution to focal defects or large tissue damage, possibly even circumventing or complementing current techniques such as microfracture and mosaicplasty. However, it is currently unclear whether implantation of decellularized cartilage in vivo may provide a mechanically and biochemically relevant platform to promote cell remodeling and repair. We examined whole decellularized osteochondral allografts implanted in the ovine trochlear groove to investigate cellular remodeling and repair tissue quality compared to empty defects and contralateral controls (healthy cartilage). At 3 months postsurgery, cells were observed in both the decellularized tissue and empty defects, although both at significantly lower levels than healthy cartilage. Qualitative and quantitative histological analysis demonstrated maintenance of cartilage features of the decellularized implant similar to healthy cartilage groups. Noninvasive analysis by quantitative magnetic resonance imaging showed no difference in T1rho and T2* between all groups. Investigation of the mechanical properties of repair tissue showed significantly lower elasticity in decellularized implants and empty defects compared to healthy cartilage, but similar tribological quantities. Overall, this study suggests that decellularized cartilage implants are subject to cellular remodeling in an in vivo environment and may provide a potential tissue engineering solution to cartilage defect interventions. PMID- 27673717 TI - Transconjunctival Approach to Scleral Fixation of Posterior Chamber Intraocular Lenses Using Gore-Tex Suture. PMID- 27673718 TI - NANN Organizes Cuban Delegation and Brings Back the Chapter Challenge for the 32nd Annual Educational Conference. PMID- 27673719 TI - Promoting Breast Milk Nutrition in Infants With Cleft Lip and/or Palate. PMID- 27673720 TI - From the Editor. PMID- 27673721 TI - Age Affects the Mitigating Efficacy of Riboflavin Against Cisplatin-Induced Toxicity In Vivo. AB - Cis-diamminedichloroplatinum (CP), a prominent anticancer drug, exerts toxic insults that are functional to various factors that compromise its antineoplastic activity. Riboflavin (RF) is an essential vitamin and photosensitizer that ameliorates CP-induced toxic insults in vivo in a dose-dependent manner. The aim of the present study is to investigate how age can influence the ameliorative effect of RF against CP-induced toxicity. Ninety male mice were divided into three age groups: young, adult, and old for the present investigation under an established treatment strategy with CP, RF, and their combinations under photoillumination for 1 mo. Their kidneys and serum samples were assessed for redox status [superoxide dismutase, catalase, reduced glutathione, malondialdehyde (MDA), carbonyl contents, and glutathione-S-transferase], biochemical analysis (renal function markers-nitric oxide), comet assay, and histopathology. The adult group showed not only the strongest resistance against the CP-induced toxicity but also the better ameliorative effect of RF followed by the young and old groups, respectively, with well-maintained redox status concomitant with the level of renal function markers, MDA, and carbonyl contents near the control values. Furthermore, comet assay and histopathological evaluation confirmed the results in a dose-dependent manner. Hence, age is an important patient-related factor that can influence the final clinical outcome under personalized chemoradiotherapy. PMID- 27673722 TI - Patients Attending Shared Medical Appointments for Metabolic Stone Prevention Have Decreased Stone Risk Factors. AB - INTRODUCTION: Shared medical appointments (SMAs) have decreased patients' wait time to initial stone clinic appointment, standardized education, and increased exposure to nutrition therapy. We assessed the effectiveness of SMAs in reducing patients' urinary stone risk factors. MATERIALS AND METHODS: Patients who established care in our stone clinic in an SMA between March 2012 and August 2015 were sequentially identified. After eliminating those without follow-up urine collections or whose urinary creatinine excretion between the two collections varied by >40%, 113 patients were included (M:F 63:50; 54 +/- 15 years; body mass index [BMI] 30.6 +/- 6.7). Results from before and after the SMA were compared with those from a similar cohort of patients who attended individual patient appointments (IPAs) for their first stone clinic visit (n = 63; M:F 37:26; 54 +/- 14 years; BMI 30.1 +/- 8.2). All patients received individualized medical therapy for stone prevention. RESULTS: After medical and nutritional therapy, SMA patients with elevated risk(s) at baseline achieved significant reductions in uric acid, calcium, and sodium; p <= 0.001 for all. Those with low urine magnesium, low urine volume, low urine pH, and/or low urine citrate at baseline achieved increases; p <= 0.0008 for all. IPA patients with elevated baseline risk factors achieved reductions in oxalate and uric acid (p <= 0.004 for both) but neither calcium nor sodium and an increase in citrate (p = 0.003) but not magnesium. CONCLUSIONS: Patients from SMAs reduced their stone recurrence risk and compared favorably with patients from IPAs. Contributing factors may include shorter time from stone event to appointment and more standardized education for patients attending SMAs. PMID- 27673724 TI - Living well with dementia groups: changes in participant and therapist verbal behaviour. AB - OBJECTIVES: This paper reports two related analyses of verbal material from seven Living Well with Dementia groups: the first examines changes in the verbal behaviours of participants across the course of the sessions in all seven groups; while the second contrasts therapist behaviour in two groups. METHODS: In the first analysis, recordings of three sessions from each group were transcribed and participant descriptions of dementia were analysed using the Markers of Assimilation of Problematic Experiences of Dementia (MAPED) rating procedure. In the second analysis, therapist behaviour in weeks 2 and 8 from two groups (F and G) was analysed using the Hill Counsellor Verbal response rating scale. Inter rater reliabilities for the two sets of ratings were 'good' and 'very good', respectively. RESULTS: For the MAPED ratings, a five by four contingency table was analysed using chi-squared, which indicated a highly significant change in assimilation. There were significant higher levels of level 1 and 2 markers in the first two sessions and level 4 for sessions 5 and 6. Facilitators used significantly more direct guidance and information giving behaviour in the second session at Location F compared to Location G. CONCLUSIONS: The results suggest that important changes occurred in the way that dementia was described across the seven LivDem groups: this includes both reductions in the avoidance of direct references to dementia after the first two sessions, as well as an increase in 'insight' statements. Directive facilitator behaviour may be associated with poorer outcomes. PMID- 27673725 TI - Is there a menopausal medicine? PMID- 27673723 TI - Gynecological Practice Represents the Ideal Setting for Early Opportunistic Cardiovascular Prevention: A Cross-Sectional Survey in an Urban Female Population. AB - BACKGROUND: Cardiovascular diseases are the main cause of mortality for women worldwide, yet their impact is frequently underestimated. To raise awareness for preventative lifestyle measures other contacts with the healthcare system should be exploited. We analyzed access patterns to other healthcare specialists and population screening measures to identify options for opportunistic counseling on cardiovascular risk. MATERIALS AND METHODS: We enrolled 1062 randomly selected German urban women aged 25-74 years in 2012-2013, divided into 5 age bands. Women were asked about sociodemographic characteristics, clinical and gynecological history, physician attendance patterns, screening behavior and primary sources of health and preventative information, and clinical examination attendance. RESULTS: Obstetrician/gynecologists (OBGYN) were the most frequently consulted physicians within the last 12 months (75.3%), more than general practitioners (GP; 74%). Attendance rates to OBGYNs were not affected by education or income, solely a body mass index (BMI) >30 associated with significantly reduced rates of attendance (OR = 0.4, CI 95% = 0.17-0.78, p = 0.009). Women with low to medium Framingham risk scores were more likely to attend an OBGYN than a GP if they attended only one specialist. Attendance of population screening measures is limited (<60% for all offers) and hence unsuitable for systematic cardiovascular counseling. CONCLUSION: OBGYN represent a very popular and equitable healthcare contact for women of all ages and this could be exploited for cardiovascular screening. Furthermore, the strikingly different sources of health information reported highlight a need for improved health communication and differentiation of messages. PMID- 27673726 TI - Examining the evolution of metals utilized in printed circuit boards. AB - Management of waste electrical and electronic equipment (WEEE) has recently attracted worldwide attention because of high metal concentrations in them. Evolution of toxic and precious metals utilized in WEEE can not only reflect the adventure of eco-design, but can also guide the final recycling option. Pb, As, Cu, Au, Sn and Ag were determined in 10 composite samples of printed circuit boards of cathode ray tube televisions (TV-PCBs) that were produced between 1980 and 2005. The obtained results indicated that average metal concentrations in all TV-PCBs were - Cu: 10.6 +/- 4.1%, Sn: 4.21 +/- 0.90%, Pb: 3.15 +/- 0.54%, Ag: 0.0215 +/- 0.0068%, Au: 0.0068 +/- 0.0049% and As: 0.0007 +/- 0.0004%. No remarkable difference was found in compositions of Pb and Sn over the years, suggesting that there were no major modifications of Sn/Pb solder used in joining the circuitry system. The average composition of Cu fluctuated between 5.10% in 1980 and 12.8% in the mid-1990s and decreased afterwards. The decreases in Ag and Cu compositions could possibly be associated with thinner layers of these metals in newer model products. PMID- 27673728 TI - The genetic basis of pigmentation in alopecia areata. AB - Alopecia areata (AA) is a common hair loss disorder characterized by discrete, well demarcated areas of non-scarring terminal hair alopecia, with the calculated lifetime risk of ~2%. In past decades, linkage and GWA studies have implicated dozens of susceptibility genes/loci that are linked to the development of AA. Fischer et al performed a genome-wide CNV analysis of 585 AA patients and 1,340 controls in a European population. This is the first genome-wide study of CNV to be performed in AA samples, and the association finding in the MCHR2 gene region further underscores the potential role of pigmentation in AA development. PMID- 27673727 TI - Global transcriptional changes caused by an EDMD mutation correlate to tissue specific disease phenotypes in C. elegans. AB - There are numerous heritable diseases associated with mutations in the LMNA gene. Most of these laminopathic diseases, including several muscular dystrophies, are autosomal dominant and have tissue-specific phenotypes. Our previous studies have shown that the globally expressed Emery-Dreifuss muscular dystrophy (EDMD)-linked lamin mutation, L535P, disrupts nuclear mechanical response specifically in muscle nuclei of C. elegans leading to atrophy of the body muscle cells and to reduced motility. Here we used RNA sequencing to analyze the global changes in gene expression caused by the L535P EDMD lamin mutation in order to gain better understanding of disease mechanisms and the correlation between transcription and phenotype. Our results show changes in key genes and biological pathways that can help explain the muscle specific phenotypes. In addition, the differential gene expression between wild-type and L535P mutant animals suggests that the pharynx function in the L535P mutant animals is affected by this lamin mutation. Moreover, these transcriptional changes were then correlated with reduced pharynx activity and abnormal pharynx muscle structure. Understanding disease mechanisms will potentially lead to new therapeutic approaches toward curing EDMD. PMID- 27673729 TI - Megacity pumping and preferential flow threaten groundwater quality. AB - Many of the world's megacities depend on groundwater from geologically complex aquifers that are over-exploited and threatened by contamination. Here, using the example of Dhaka, Bangladesh, we illustrate how interactions between aquifer heterogeneity and groundwater exploitation jeopardize groundwater resources regionally. Groundwater pumping in Dhaka has caused large-scale drawdown that extends into outlying areas where arsenic-contaminated shallow groundwater is pervasive and has potential to migrate downward. We evaluate the vulnerability of deep, low-arsenic groundwater with groundwater models that incorporate geostatistical simulations of aquifer heterogeneity. Simulations show that preferential flow through stratigraphy typical of fluvio-deltaic aquifers could contaminate deep (>150 m) groundwater within a decade, nearly a century faster than predicted through homogeneous models calibrated to the same data. The most critical fast flowpaths cannot be predicted by simplified models or identified by standard measurements. Such complex vulnerability beyond city limits could become a limiting factor for megacity groundwater supplies in aquifers worldwide. PMID- 27673730 TI - De novo transcriptome assembly databases for the butterfly orchid Phalaenopsis equestris. AB - Orchids are renowned for their spectacular flowers and ecological adaptations. After the sequencing of the genome of the tropical epiphytic orchid Phalaenopsis equestris, we combined Illumina HiSeq2000 for RNA-Seq and Trinity for de novo assembly to characterize the transcriptomes for 11 diverse P. equestris tissues representing the root, stem, leaf, flower buds, column, lip, petal, sepal and three developmental stages of seeds. Our aims were to contribute to a better understanding of the molecular mechanisms driving the analysed tissue characteristics and to enrich the available data for P. equestris. Here, we present three databases. The first dataset is the RNA-Seq raw reads, which can be used to execute new experiments with different analysis approaches. The other two datasets allow different types of searches for candidate homologues. The second dataset includes the sets of assembled unigenes and predicted coding sequences and proteins, enabling a sequence-based search. The third dataset consists of the annotation results of the aligned unigenes versus the Nonredundant (Nr) protein database, Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) databases with low e-values, enabling a name-based search. PMID- 27673731 TI - Eye movement as a biomarker of schizophrenia: Using an integrated eye movement score. AB - AIM: Studies have shown that eye movement abnormalities are possible neurophysiological biomarkers for schizophrenia. The aim of this study was to investigate the utility of eye movement abnormalities in identifying patients with schizophrenia from healthy controls. METHODS: Eighty-five patients with schizophrenia and 252 healthy controls participated in this study. Eye movement measures were collected from free viewing, fixation stability, and smooth pursuit tests. In an objective and stepwise method, eye movement measures were extracted to create an integrated eye movement score. RESULTS: The discriminant analysis resulted in three eye movement measures; the scanpath length during the free viewing test, the horizontal position gain during the fast Lissajous paradigm of the smooth pursuit test, and the duration of fixations during the far distractor paradigm of the fixation stability test. An integrated score using these variables can distinguish patients with schizophrenia from healthy controls with 82% accuracy. The integrated score was correlated with Wechsler Adult Intelligence Scale-Third Edition full scale IQ, Positive and Negative Syndrome Scale scores, and chlorpromazine equivalents, with different correlation patterns in the three eye movement measures used. The discriminant analysis in subgroups matched for age, sex, years of education, and premorbid IQ revealed a sustained classification rate. CONCLUSION: We established an integrated eye movement score with high classification accuracy between patients with schizophrenia and healthy controls, although there was a significant effect of medication. This study provides further evidence of the utility of eye movement abnormalities in schizophrenia pathology and treatment. PMID- 27673732 TI - Foster Care Outcomes for Children With Intellectual Disability. AB - The promotion of speedy, permanent outcomes for foster children is a central child welfare policy goal. However, while children with intellectual disability (ID) are at greater risk for child welfare involvement, little is known about their case outcomes. This cross-sectional national study explores between-group foster care outcomes. Foster children with intellectual disability were more likely to have experienced an adoption disruption or dissolution but less likely to be reunified with a parent, primary caretaker or other family member. Implications for interagency collaboration in support of pre and post-foster care discharge support services are discussed. PMID- 27673734 TI - Sibling Caregivers of People With Intellectual and Developmental Disabilities: Sociodemographic Characteristics and Material Hardship Prevalence. AB - In growing numbers, people with intellectual and developmental disabilities are outliving their parents, or at least their parents' ability to care for them. Consequently, adult siblings without intellectual and developmental disabilities are increasingly taking on primary caregiving responsibilities. However, adult siblings have received little study generally, and sibling caregivers have received even less. We used nationally representative data from the Survey of Income and Program Participation (SIPP) to describe the social characteristics and material hardship levels of sibling caregivers, in comparison to the general working age adult population. This study finds moderate material hardship to be pervasive among sibling caregivers, though extreme levels of hardship are possibly being abated somewhat through public benefit programs. Implications for greater service needs are discussed. PMID- 27673733 TI - Culture in Better Group Homes for People With Intellectual Disability at Severe Levels. AB - Building on cultural dimensions of underperforming group homes this study analyses culture in better performing services. In depth qualitative case studies were conducted in 3 better group homes using participant observation and interviews. The culture in these homes, reflected in patterns of staff practice and talk, as well as artefacts differed from that found in underperforming services. Formal power holders were undisputed leaders, their values aligned with those of other staff and the organization, responsibility for practice quality was shared enabling teamwork, staff perceived their purpose as "making the life each person wants it to be," working practices were person centered, and new ideas and outsiders were embraced. The culture was characterized as coherent, respectful, "enabling" for residents, and "motivating" for staff. Though it is unclear whether good group homes have a similar culture to better ones the insights from this study provide knowledge to guide service development and evaluation. PMID- 27673735 TI - Outdated Language: Use of "Mental Retardation" in Medicaid HCBS Waivers Post Rosa's Law. AB - Rosa's Law, which changed references of "mental retardation" to "intellectual disability" within federal legislation, marked recognition by the federal government that the term "mental retardation" is outdated and pejorative. However, Rosa's Law did not apply to many notable federal programs related to disability, such as Medicaid. This article explores if and how the term "mental retardation" was used within Medicaid Home and Community Based Services 1915(c) waivers, as they are the most prevalent provider of long-term services and supports for people with intellectual and developmental disabilities. Waivers provide some of the most advanced community services and the language used in them should reflect this. Although an overwhelming majority of waivers used "mental retardation," we found that the term was used less for later benchmark dates. PMID- 27673736 TI - Systemwide Initiative Documents Robust Health Screening for Adults With Intellectual Disability. AB - It is well documented that adults with intellectual disability (ID) experience higher rates of a series of health conditions compared to their peers without disability. These health conditions include cardiovascular disease, obesity, diabetes, gastrointestinal disorders, and psychiatric and behavioral disorders. With life expectancy approximating the general population, adults with ID are also now experiencing health conditions related to aging, further increasing their risk for diminished function and well-being. This increased morbidity poses new challenges in geriatric healthcare planning for this population. Relatively simple health prevention practices, such as the implementation of a health screening tool, can substantially increase disease detection and clinical activities directed toward improved health outcomes for people with ID. This study examines data collected from the District of Columbia Developmental Disabilities Administration's (DC DDA's) health screening component of its Health and Wellness Standards. Findings are presented, along with recommendations and implications for improving preventive health screening practices in the ID population. PMID- 27673737 TI - The Reinforcement of Ableism: Normality, the Medical Model of Disability, and Humanism in Applied Behavior Analysis and ASD. AB - The field of educating individuals with Autism Spectrum Disorder has ever been rife with controversy regarding issues ranging from etiology and causation to effective intervention and education options. One such basis for controversy has been between humanism, and humanistic philosophical concepts, and its fundamental differences with behaviorism, and behavioristic philosophical concepts. These differences have long been debated, and the belief that the two orientations are generally mutually exclusive has been largely maintained. Recently, however, there has been some resurgence of interest in reconciling some of the fundamental humanistic and behavioristic tenets. Most of these discussions, however, center on specific interventional methodologies as its basis without delving more deeply into the underlying philosophical issues. This article will explore some fundamental humanistic concepts that ought to be reconciled in order for behaviorism to be considered a humanistic practice. While the notion that the possibility of reconciliation is maintained, the central argument maintains that much work needs to be done on the part of behaviorism both philosophically and methodologically in order for such reconciliation to be achieved. PMID- 27673740 TI - Erratum. PMID- 27673742 TI - Colloidal Mechanisms of Gold Nanoparticle Loss in Asymmetric Flow Field-Flow Fractionation. AB - Flow field-flow fractionation is a powerful method for the analysis of nanoparticle size distributions, but its widespread use has been hampered by large analyte losses, especially of metal nanoparticles. Here, we report on the colloidal mechanisms underlying the losses. We systematically studied gold nanoparticles (AuNPs) during asymmetrical flow field-flow fractionation (AF4) by systematic variation of the particle properties and the eluent composition. Recoveries of AuNPs (core diameter 12 nm) stabilized by citrate or polyethylene glycol (PEG) at different ionic strengths were determined. We used online UV-vis detection and off-line elementary analysis to follow particle losses during full analysis runs, runs without cross-flow, and runs with parts of the instrument bypassed. The combination allowed us to calculate relative and absolute analyte losses at different stages of the analytic protocol. We found different loss mechanisms depending on the ligand. Citrate-stabilized particles degraded during analysis and suffered large losses (up to 74%). PEG-stabilized particles had smaller relative losses at moderate ionic strengths (1-20%) that depended on PEG length. Long PEGs at higher ionic strengths (>=5 mM) caused particle loss due to bridging adsorption at the membrane. Bulk agglomeration was not a relevant loss mechanism at low ionic strengths <=5 mM for any of the studied particles. An unexpectedly large fraction of particles was lost at tubing and other internal surfaces. We propose that the colloidal mechanisms observed here are relevant loss mechanisms in many particle analysis protocols and discuss strategies to avoid them. PMID- 27673743 TI - Improvement of the Thermal and Optical Performances of Protective Polydimethylsiloxane Space Coatings with Cellulose Nanocrystal Additives. AB - This work investigates the possibility of using cellulose nanocrystals (CNCs) as biobased nanoadditives in protective polydimethylsiloxane (PDMS) space coatings, to improve the thermal and optical performances of the material. CNCs produced from wood pulp were functionalized in different conditions with the objective to improve their dispersibility in the PDMS matrix, increase their thermal stability and provide photoactive functions. Polysiloxane, cinnamate, chloroacetate and trifluoroacetate moieties were accordingly anchored at the CNCs surface by silylation, using two different approaches, or acylation with different functional vinyl esters. The modified CNCs were thoroughly characterized by FT-IR spectroscopy, solid-state NMR spectroscopy and thermogravimetric analysis, before being incorporated into a PDMS space coating formulation in low concentration (0.5 to 4 wt %). The cross-linked PDMS films were subsequently investigated with regards to their mechanical behavior, thermal stability and optical properties after photoaging. Results revealed that the CNC additives could significantly improve the thermal stability of the PDMS coating, up to 140 degrees C, depending on the treatment and CNC concentration, without affecting the mechanical properties and transparency of the material. In addition, the PDMS films loaded with as low as 1 wt % halogenated nanoparticles, exhibited an improved UV-stability after irradiation in geostationary conditions. PMID- 27673741 TI - Regional Gray Matter Volume Loss Is Associated with Gait Impairments in Young Brain-Injured Individuals. AB - Traumatic brain injury (TBI) often leads to impairments in gait performance. However, the underlying neurostructural pathology of these gait deficits is poorly understood. We aimed to investigate regional gray matter (GM) volume in young moderate-to-severe TBI participants (n = 19; age 13 years 11 months +/-3 years 1 month), compared with typically developing (TD) participants (n = 30; 14 years 10 months +/-2 years 2 months), and assess whether reduced volume was related to impaired gait performance in TBI participants. Cortical and subcortical GM structures involved in the neural control of gait were selected as regions of interest (ROIs) and their volume was extracted using Freesurfer. Moreover, established spatiotemporal markers of gait impairments in TBI participants, including step length asymmetry, step length variability, and double support time, were obtained using an electronic walkway. Compared with TD participants, TBI participants showed increased double support time, step length asymmetry, and step length variability, suggesting a reduced gait control. Secondly, in TBI participants, reduced volumes were demonstrated in overall subcortical GM and individual subcortical ROIs, including the hippocampus, cerebellar cortex, putamen, and thalamus. Moreover, in the TBI group, volume losses in subcortical ROIs were highly inter-correlated, indicating that atrophy tends to occur in combined subcortical structures. Finally, it was demonstrated, for the first time, that gait abnormalities in TBI subjects were associated with reduced volume in specific GM structures, including the hippocampus, thalamus, and the cerebellar, superior frontal, paracentral, posterior cingulate, and superior parietal cortices. The present study is an important first step in the understanding of the neurostructural pathology underlying impaired gait in TBI patients. PMID- 27673744 TI - Location of the tibial tunnel aperture affects extrusion of the lateral meniscus following reconstruction of the anterior cruciate ligament. AB - The anterior root of the lateral meniscus provides functional stability to the meniscus. In this study, we evaluated the relationship between the position of the tibial tunnel and extrusion of the lateral meniscus after anterior cruciate ligament reconstruction, where extrusion provides a proxy measure of injury to the anterior root. The relationship between extrusion and tibial tunnel location was retrospectively evaluated from computed tomography and magnetic resonance images of 26 reconstructed knees, contributed by 25 patients aged 17-31 years. A measurement grid was used to localize the position of the tibial tunnel based on anatomical landmarks identified from the three-dimensional reconstruction of axial computed tomography images of the tibial plateaus. The reference point-to tibial tunnel distance (mm) was defined as the distance from the midpoint of the lateral edge of the grid to the posterolateral aspect of the tunnel aperture. The optimal cutoff of this distance to minimize post-operative extrusion was identified using receiver operating curve analysis. Extrusion of the lateral meniscus was positively correlated to the reference point-to-tibial tunnel distance (r 2 = 0.64; p < 0.001), with a cutoff distance of 5 mm having a sensitivity to extrusion of 83% and specificity of 93%. The mean extrusion for a distance >5 mm was 0.40 +/- 0.43 mm, compared to 1.40 +/- 0.51 mm for a distance <=5 mm (p < 0.001). Therefore, a posterolateral location of the tibial tunnel aperture within the footprint of the anterior cruciate ligament decreases the reference point-to-tibial tunnel distance and increases extrusion of the lateral meniscus post-reconstruction. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1625-1633, 2017. PMID- 27673745 TI - Regioselective 5-O-Opening of Conformationally Locked 3,5-O-Di-tert-butylsilylene d-galactofuranosides. Synthesis of (1->5)-beta-d-Galactofuranosyl Derivatives. AB - The use of thiogalactofuranoside as donors for the construction of internal Galf containing oligosaccharide is limited, probably due to the difficulty to functionalize thiogalactofuranoside derivatives showing O-2, O-3, and O-5 with similar reactivity. An efficient method for complete regioselective 5-O-opening of conformationally restricted 3,5-O-di-tert-butylsilylene-d-galactofuranoside derivatives was developed. The use of a solution nBu4NF (1.1 equiv) in CH2Cl2 on 6 gave the 5-OH free derivative 10 as the only product (90%). 3-O-Di-tert butylhydroxysilyl derivative 10 was stable upon purification and glycosylation reaction. Preactivation of conformationally restricted thioglycoside 6 employing p-NO2-benzensulfenyl chloride/AgOTf followed by condensation over the 5-OH thioglycoside acceptor 10 gave the corresponding disaccharide 12 without autocondensation byproduct. Regioselective 5-O-deprotection was also successfully performed over the (1->5)-beta-d-galactofuranosyl di- and trisaccharide derivatives 12 and 13. This methodology allowed the differentiation between the secondary hydroxyl groups OH-3 and OH-5 of 1,2-cis or 1,2-trans d galactofuranoside derivatives, and it still constitutes an innovative approach to access oligosaccharides of pharmacological importance. PMID- 27673748 TI - Immediate Implant Placement of a Single Central Incisor Using a CAD/CAM Crown Root Form Technique: Provisional to Final Restoration. AB - OBJECTIVE: Preserving soft and hard tissues after extraction and implant placement is crucial for anterior esthetics. This technique will show how the information gathered from a cone-beam computed tomography (CBCT) scan of the maxillary left central incisor and an intra-oral digital impression can be merged to fabricate a CAD/CAM crown-root matrix to be used as an immediate provisional restoration that mimics the natural anatomy. CLINICAL CONSIDERATIONS: Due to trauma, a left central incisor appeared to be fractured and was scheduled for extraction and implant placement. The crown-root configuration captured by the CBCT scan was merged with the digital files from an intra-oral digital impression. A CAD/CAM crown-root matrix was fabricated. Because the matrix shell was fabricated with the exact anatomy of the natural tooth, it replicated the position and three dimensional anatomy of the soft and hard tissue. It was connected to the implant with a customized provisional abutment. A digital impression of a coded healing abutment was made to fabricate the final implant abutment and final restoration. Throughout the treatment time and 36 months after completion, the thickness of tissue, emergence profile, and adjacent papilla was analyzed by clinical evaluation and photography and seemed to be maintained. CONCLUSION: The use of a pre-operative intra-oral digital scan of the clinical crown-root architecture and the CBCT scan of the bone/root anatomy, can be used together to fabricate a CAD/CAM crown-root form provisional matrix. This digital design helps in the preservation of the 3D tissue topography, as well as the final restoration. CLINICAL SIGNIFICANCE: The preservation of soft and hard tissue after extraction and implant placement has always been paramount for ideal anterior implant esthetics. Using the information from digital files from CBCT scans and intra-oral scans may help the clinician identify critical anatomical features that can be replicated in the provisional and final CAD/CAM restoration. (J Esthet Restor Dent 29:13-21, 2017). PMID- 27673747 TI - Regulation of development of rat stem and progenitor Leydig cells by activin. AB - Stem Leydig cells have been demonstrated to differentiate into adult Leydig cells via intermediate stages of progenitor and immature Leydig cells. However, the exact regulatory mechanisms are unclear. We hypothesized that the development of stem or progenitor Leydig cells depends upon locally produced growth factors. Microarray analysis revealed that the expression levels of activin type I receptor (Acvr1) and activin A receptor type II-like 1 (Acvrl1) were stem > progenitor = immature = adult Leydig cells. This indicates that their ligand activin might play an important role in stem and progenitor Leydig cell proliferation and differentiation. When seminiferous tubules were incubated with 1 or 10 ng/mL activin A for 3 days, it concentration-dependently increased EdU incorporation into stem Leydig cells by up to 20-fold. When progenitor Leydig cells were incubated with 1 or 10 ng/mL activin A for 2 days, it concentration dependently increased 3 H-thymidine incorporation into progenitor Leydig cells by up to 200%. Real-time PCR analysis showed that activin A primarily increased Pcna expression but reduced Star, Hsd3b1, and Cyp17a1 expression levels. Activin A also significantly inhibited the basal and luteinizing hormone-stimulated androgen production. In conclusion, activin A primarily stimulates the proliferation of stem and progenitor Leydig cells, but inhibits the differentiation of stem and progenitor Leydig cells into the Leydig cell lineage in rat testis. PMID- 27673746 TI - Apoptotic properties of the type 1 interferon induced family of human mitochondrial membrane ISG12 proteins. AB - BACKGROUND INFORMATION: Interferons are a family of cytokines with growth inhibitory and antiviral functions, which exert their biological actions through the expression of interferon-stimulated genes (ISGs). The human ISG12 family of proteins comprises ISG12A, ISG12B, ISG12C and ISG6-16. Due to differential splicing and a gene variation, the human ISG12A protein exists as a full-length ISG12A form and three ISG12A variants. ISG12 genes have been found transcriptionally dysregulated in many disorders. High levels of ISG12A mRNA have been found in breast and ovarian cancers. Loss of heterozygosity at the position of the ISG12 genes often occurs in ovarian carcinomas and lymphoblastic leukemias. Both ISG12A and ISG6-16 are up-regulated in psoriasis. RESULTS: We demonstrate here that expression of the human full-length ISG12A protein sensitises cells for TNFalpha and the BH3 mimetic gossypol induced apoptosis, and the other ISG12A variants as well as ISG12B and ISG12C can induce apoptosis directly in HEK293 cells. Also ISG6-16 sensitises HEK293 cells for gossypol induced apoptosis. In the ISG12 motif, two putative Bcl-2 homology (BH)3 like motifs were found, which may be decisive for the apoptotic properties of the ISG12 proteins. A series of BH3 mutants was made in ISG12ADelta-S, the smallest apoptosis-inducing ISG12A variant and our results indicate that ISG12ADelta-S indeed possesses features resembling those of BH3-only proteins. Supporting this notion are our findings that the full-length ISG12A co-immunoprecipitates with the Bcl-2 protein, and the apoptotic properties of the ISG12A variants are reduced in Bcl-2 expressing HEK293 cells. In addition, full-length ISG12A is able to form homodimers, which suggests a possible involvement in pore formation during apoptosis. The full-length ISG12A, the three ISG12A variants and the ISG12B proteins were found to be localised in the mitochondria. CONCLUSIONS: Our results suggest that the ISG12 family of proteins has an important role for the apoptotic properties induced by type 1 interferon. SIGNIFICANCE: The ISG12 family constitute small hydrophic proteins involved in apoptosis. This is the first comparison of the apoptotic potentials of the full-length ISG12A protein and the three ISG12A variants. The differential apoptotic potentials of these proteins might have an impact on the strategies to monitor and interpret their dysregulation associated with many disorders. PMID- 27673749 TI - How to prepare a manuscript fit-for-purpose for submission and avoid getting a 'desk-reject'. AB - First impressions are very important and, when these are negative, they can adversely affect a manuscript's journey through the scientific publication system. This short guide highlights some crucial factors to take into consideration before submitting a manuscript for review in a scientific journal. The aim is to advise authors on the best way to present their research, to comply with formal requirements of a journal and to optimize the first impression made. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27673750 TI - A changing of the guard. PMID- 27673751 TI - Distorted Tetrahedral CoII in K5H[CoW12O40].xH2O Probed by 2p3d Resonant Inelastic X-ray Scattering. AB - The Co 2p3/2 X-ray absorption spectroscopy and high-energy-resolution (~0.09 eV fwhm) 2p3d resonant inelastic X-ray scattering (RIXS) spectra of the single cobalt-centered polyoxometalate K5H[CoW12O40].xH2O were measured. The low-energy dd transition features at 0.55 eV, unmeasurable with ultraviolet-visible (UV/vis) spectroscopy, were experimentally revealed in 2p3d RIXS spectra. RIXS simulations based on ligand-field multiplet theory were performed to assess the potential cobalt tetragonal symmetry distortion, which is described with the ligand-field parameters 10Dq (-0.54 eV), Ds (-0.08 eV), and Dt (0.005 eV). Because 2p3d RIXS probes not only the optical spin-allowed transitions but also the spin-forbidden transitions, we show that the current 2p3d RIXS simulation enables a series of dd feature assignments with higher accuracy than those from previous optical data. Furthermore, by wave-function decomposition analyses, we demonstrate the more realistic and detailed origins of a few lowest dd transitions using both one electron-orbital and term-symbol descriptions. PMID- 27673752 TI - Pancreatic Gastrointestinal Stromal Tumor: Clinicopathologic Features and Prognosis. AB - GOALS: The present study aimed to investigate the clinicopathologic features and prognosis of pancreatic gastrointestinal stromal tumor (GIST). BACKGROUND: Reports on clinicopathologic features and prognosis of pancreatic GIST are limited due to the extremely rare incidence. STUDY: One case of pancreatic GIST from our center and 44 cases reported in MEDLINE were enrolled in this study. Clinicopathologic features and prognosis of pancreatic GISTs were analyzed and compared with 297 gastric GISTs from our center. RESULTS: The most common location was head of pancreas (38.5%). The majority of pancreatic GISTs exceeded 5 cm (74.4%), displayed cystic or mixed imaging features (56.4%), and were high risk (85.7%). The 5-year disease-free survival (DFS) and disease-specific survival rates were 66.1% and 95.8%, respectively. Mitotic index was the only risk factor for DFS of pancreatic GISTs. The distribution of tumor size, histologic type and National Institutes of Health risk category were significantly different between pancreatic and gastric GISTs. The 5-year DFS rate of pancreatic GISTs was significantly lower than that of gastric GISTs. Multivariate analysis showed that location was an independent prognostic factor for DFS between pancreatic and gastric GISTs. CONCLUSIONS: The most common location was head of pancreas. The majority of pancreatic GISTs were large and highly malignant. Pancreatic GISTs differed significantly from gastric GISTs in respect to clinicopathologic features. The DFS of pancreatic GISTs was worse than that of gastric GISTs. PMID- 27673753 TI - High Prevalence of Medication Discrepancies Between Home Health Referrals and Centers for Medicare and Medicaid Services Home Health Certification and Plan of Care and Their Potential to Affect Safety of Vulnerable Elderly Adults. AB - OBJECTIVES: To describe the prevalence of discrepancies between medication lists that referring providers and home healthcare (HH) nurses create. DESIGN: The active medication list from the hospital at time of HH initiation was compared with the HH agency's plan of care medication list. An electronic algorithm was developed to compare the two lists for discrepancies. SETTING: Single large hospital and HH agency in the western United States. PARTICIPANTS: Individuals referred for HH from the hospital in 2012 (N = 770, 96.3% male, median age 71). MEASUREMENTS: Prevalence was calculated for discrepancies, including medications missing from one list or the other and differences in dose, frequency, or route for medications contained on both lists. RESULTS: Participants had multiple medical problems (median 16 active problems) and were taking a median of 15 medications (range 1-93). Every participant had at least one discrepancy; 90.1% of HH lists were missing at least one medication that the referring provider had prescribed, 92.1% of HH lists contained medications not on the referring provider's list, 89.8% contained medication naming errors. 71.0% contained dosing discrepancies, and 76.3% contained frequency discrepancies. CONCLUSION: Discrepancies between HH and referring provider lists are common. Future work is needed to address possible safety and care coordination implications of discrepancies in this highly complex population. PMID- 27673754 TI - Transcutaneous Carbon Dioxide Monitoring with Reduced-Temperature Probes in Very Low Birth Weight Infants. AB - Background Obtaining blood gases in very low birth weight (VLBW) infants is an invasive procedure. Studies using transcutaneous carbon dioxide (tcPCO2) have reported variable skin complications with high-temperature probes. No enough data available on tcPCO2 monitoring using reduced-temperature probes (41 degrees C). Objective The objective of this study was to assess reliability and safety of tcPCO2 monitoring at reduced-temperature probe in VLBW infants. Design and Methods A prospective study was conducted on VLBW infants. tcPCO2 was monitored for 12 hours. Default skin probe temperature was adjusted at 41 degrees C. Blood gases were done as clinically indicated. Arterial partial pressure of CO2 (PaCO2) as well as capillary CO2 were compared with simultaneous tcPCO2. Results A total of 124 data points were identified from 50 patients (gestational age [GA] = 28.1 +/- 2.4 weeks and birth weight [BW] = 1,035 +/- 291 g). Patients were supported with continuous positive airway pressure (40%), noninvasive positive pressure ventilation (16%), mechanical ventilation (18%), and high-frequency oscillation ventilation (24%). PaCO2 was measured using either capillary (58%) or arterial (42%) samples. Mean CO2 did not differ between tcPCO2 (51.3 +/- 16) and PaCO2 (49.1 +/- 13.7) mm Hg. tcPCO2 showed positive correlation with partial pressure of CO2 (r = 0.6, p < 0.001). This correlation continued to be significant after controlling for GA, postmenstrual age, type of sample, and pH. No skin complications were reported. Conclusion tcPCO2 monitoring using a temperature of 41 degrees C is feasible and reliable in VLBW infants. PMID- 27673756 TI - Ab Initio Potential for H3O+ -> H+ + H2O: A Step to a Many-Body Representation of the Hydrated Proton? AB - We report a new potential energy surface (PES) for hydronium that dissociates to H+ + H2O. The PES is a permutationally invariant fit to a data set of nearly 100,000 electronic energies, of which most are CCSD(T)-F12/aug-cc-pVQZ, plus a small set of MRCI-aug-cc-pVTZ diabatic energies in the region where the CCSD(T) method fails. The long-range part of the PES is described accurately by a classical Coulomb interaction between the proton and H2O using partial charges obtained from an accurate, full-dimensional dipole moment surface. A switching function connects the fitted PES to this long-range interaction.The fidelity of this global PES is determined by a combination of standard geometry and harmonic analyses at the minimum and inversion saddle point. In addition, VSCF/VCI calculations of the fundamentals and tunneling splittings are reported; all of these are within 3 cm-1 or less of experimental values. A diffusion Monte Carlo calculation is also reported for the zero-point state. The PES is used in a two body representation of the interaction of the proton with two water molecules, including a 2-body H2O-H2O interaction, and is shown to give a realistic description of the Zundel cation H5O2+. This demonstrates that the PES may be usable as a component in a many-body potential describing the hydrated proton, especially for vibrational calculations of protonated water clusters. PMID- 27673755 TI - Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons. AB - INTRODUCTION: 18F-Fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human beta-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about 18F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of 18F-FP-(+)-DTBZ and its inactive enantiomer 18F-FP-(-)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions. METHODS: PET scans were conducted for up to 4h with (+) and (-) enantiomers. Displacement experiments using unlabeled (+) and (-) enantiomers of FP-DTBZ and fluvoxamine (to evaluate sigma-1 receptor binding) were performed. SUV curves were used to calculate displacement values in the pancreas, renal cortex, and spleen. Distribution volumes (VT) were computed, and three approaches for calculation of VND were compared: (1) 18F-FP-(+)-DTBZ reference VT, (2) 18F FP-(-)-DTBZ pancreatic VT, and (3) a scaled 18F-FP-(+)-DTBZ reference VT values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90min post-injection. RESULTS: Spleen uptake was lowest for both tracers. Highest uptake was in the pancreas with 18F-FP-(+)-DTBZ and renal cortex with 18F-FP-(-)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the 18F-FP-(+)-DTBZ studies. Radiometabolite fraction was higher in the renal cortex than the spleen. Approaches (1) and (3) with spleen to estimate VND provided lowest inter-subject variability of BPND. CONCLUSIONS: VT differences among organs and between enantiomers indicated that scaling of reference region values is needed for quantification of VMAT2 binding in the pancreas with 18F-FP-(+)-DTBZ. Since the kidney PET signal has greater partial volume averaging and more radiometabolites, the spleen was considered a more practical candidate for use as a scaled reference region in the quantification of 18F-FP-(+)-DTBZ in the pancreas. PMID- 27673757 TI - Detection of different categories of hepatitis B virus (HBV) infection in a multi regional study comparing the clinical sensitivity of hepatitis B surface antigen and HBV-DNA testing. AB - BACKGROUND: Twenty-two users of individual donation nucleic acid amplification technology (ID-NAT) in six geographical regions provided detailed hepatitis B virus (HBV) infection data in first-time, lapsed, and repeat donations and classified confirmed HBV-positive donors into different infection categories. These data were used to compare the clinical sensitivity of hepatitis B surface antigen (HBsAg) and HBV-DNA testing. STUDY DESIGN AND METHODS: In total 10,981,776 donations from South Africa, Egypt, the Mediterranean, North and Central Europe, South East Asia, and Oceania were screened for HBV-DNA using the Ultrio assay (Grifols/Hologic) and for HBsAg using a chemiluminescence immunoassay, and 9455 HBV-infected donations were identified. HBsAg-negative window period (WP), HBsAg-positive and occult HBV infection (OBI) stages were determined using supplemental serology, quantitative polymerase chain reaction, and replicate multiplex and discriminatory HBV NAT test strategies. For two regions, additional data sets using the more sensitive Ultrio Plus assay were assessed. RESULTS: Regional HBV detection rates in first-time donors varied between 0.08% and 1.07%, with WP NAT yield rates varying between 1:7700 and 1:294,000 and OBI NAT yield rates varying from 1:3900 to 1:59,000. HBsAg CLIA detected 97.0% of infections in first-time donors, 62.7% in lapsed donors, and 41.0% in repeat donors; whereas Ultrio detected 93.1%, 95.0%, and 98.3% of infections in these respective groups. HBV-DNA detection rates in HBsAg-positive donors varied from 90.2% to 96.3% between regions but increased significantly (range, 95.2-98.2%) with the Ultrio Plus assay. CONCLUSION: ID-NAT and serology are complementary in detecting HBV infection in first-time donors, but HBV-DNA is superior to HBsAg detection in repeat donors. PMID- 27673858 TI - The Role of Stereotactic Radiosurgery in the Reirradiation of Metastatic Spinal Tumors. PMID- 27673859 TI - A Phase I/II Trial of 5 Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme. PMID- 27673860 TI - Initial Report on Safety and Lesion Response of Melanoma Brain Metastases After Stereotactic Radiosurgery or Hypofractionated Radiation Therapy in Patients Receiving Concurrent Pembrolizumab. PMID- 27673861 TI - Clinical and Quality of Life Implications of Vertebral Compression Fracture Following Spine Radiosurgery. PMID- 27673862 TI - Comparison of Invasive and Noninvasive Frame for Set-up Error Accuracy in Intracranial Radiation Therapy-An Indian Institute Experience. PMID- 27673863 TI - Echoplanar Magnetic Resonance Spectroscopic Imaging Before and Following Radiation Therapy in Patients With High-Grade Glioma. PMID- 27673864 TI - Exploration of an Appropriate Threshold Value of a Novel 18F-ALF-NOTA-PRGD2 Positron Emission Tomography/Computed Tomography to Contour Tumor Volume of Glioblastoma Multiforme. PMID- 27673865 TI - Influence of Molecular Subgroups and Systemic Therapy on Outcomes of Metastatic Breast Cancer Patients Receiving Stereotactic Radiosurgery for Brain Metastases. PMID- 27673866 TI - Imaging and Clinical Profile Following Concurrent Stereotactic Radiation and Immune Therapy for Melanoma Brain Metastases: Preliminary Results. PMID- 27673867 TI - A Comparison of Brain and Hippocampal Dosimetry With Protons or Intensity Modulated Radiation Therapy Planning for Unilateral Glioblastoma. PMID- 27673868 TI - Outcomes for Metastatic Melanoma Treated With Stereotactic Radiosurgery In the Era of Targeted Systemic Therapies. PMID- 27673869 TI - Low Levels of Acute Toxicity Associated With Proton Therapy for Low-Grade Glioma: A Proton Collaborative Group Study. PMID- 27676070 TI - Thermal Decomposition of Isopropyl Nitrate: Kinetics and Products. AB - Kinetics and products of the thermal decomposition of isopropyl nitrate (IPN, C3H7NO3) have been studied using a low pressure flow reactor combined with a quadrupole mass spectrometer. The rate constant of IPN decomposition was measured as a function of pressure (1-12.5 Torr of helium) and temperature in the range 473-658 K using two methods: from kinetics of nitrate loss and those of reaction product (CH3 radical) formation. The fit of the observed falloff curves with two parameter expression [Formula: see text] provided the following low and high pressure limits for the rate constant of IPN decomposition: k0 = 6.60 * 10-5exp( 15190/T) cm3 molecule-1 s-1 and kinfinity = 1.05 * 1016 exp(-19850/T) s-1, respectively, which allows one to determine (via the above expression) the values of k1 (with 20% uncertainty) in the temperature and pressure range of the study. It was observed that thermal decomposition of IPN proceeds through initial breaking of the O-NO2 bond, leading to formation of NO2 and isopropoxy radical (CH3)2CHO, which rapidly decomposes forming CH3 and acetaldehyde as final products. The yields of NO2, CH3, and acetaldehyde upon decomposition of isopropyl nitrate were measured to be (0.98 +/- 0.15), (0.96 +/- 0.14), and (0.99 +/- 0.15), respectively. In addition, the kinetic data were used to determine the O-NO2 bond dissociation energy in isopropyl nitrate, 38.2 +/- 4.0 kcal mol-1. PMID- 27676071 TI - Dietary Reversal Ameliorates Short- and Long-Term Memory Deficits Induced by High fat Diet Early in Life. AB - A high-fat diet (HFD), one of the major factors contributing to metabolic syndrome, which is associated with an increased risk of neurodegenerative diseases, leads to insulin resistance and cognitive impairment. It is not known whether these alterations are improved with dietary intervention. To investigate the long-term impact of a HFD on hippocampal insulin signaling and memory, C57BL6 mice were placed into one of three groups based on the diet: a standard diet (control), a HFD, or a HFD for 16 weeks and then the standard diet for 8 weeks (HF16). HFD-induced impairments in glucose tolerance and hippocampal insulin signaling occurred concurrently with deficits in both short- and long-term memory. Furthermore, these conditions were improved with dietary intervention; however, the HFD-induced decrease in insulin receptor expression in the hippocampus was not altered with dietary intervention. Our results demonstrate that memory deficits due to the consumption of a HFD at an early age are reversible. PMID- 27676074 TI - Selective deuteration of [(pyridylmethyl)sulfinyl]benzimidazole antisecretory drugs. A NMR study where DMSO-d6 acts as deuteration agent. AB - The use of deuterated drug bioisosteres to obtain superior pharmacokinetic properties or to investigate biotransformations at the molecular level is a growing field of pharmaceutical research. This work presents a NMR study on the deuteration of three structurally related antisecretory proton-pump inhibitors, the sodium salts of esomeprazole, 1, pantoprazole, 2, and rabeprazole, 3. It has been found that the methylene adjacent to the sulfinyl group displays stereoselective deuteration when the sodium salts of these products are dissolved at room temperature in D2O or CD3OD, a process that also occurs very efficiently in DMSO-d6 (a solvent considered non-deuterating) if a catalytic amount of NaOH is added. The stereoselectivity of the deuteration is consequence of the asymmetry around the sulfur atom of the sulfinyl group, and the rate of the H-D exchange seems to be mainly related to the polarity of the solvents. In addition, unusually long-range (up to seven bonds) NMR deuterium isotopic effects on proton have been detected. Density Functional Theory (DFT) calculations (DFT/6-31G**) have been performed on the rotamers about the CH2SO bond of 1, as well as about the equivalent bond in its entiol, N-anion, and entiolate. Less conformers than possible were obtained in all cases indicating strong preference for some spatial dispositions. Computed NMR shielding agrees with the experimentally obtained chemical shifts and help in identifying the most accessible diastereotopic hydrogen. PMID- 27676073 TI - PARAQUAT TOLERANCE3 Is an E3 Ligase That Switches off Activated Oxidative Response by Targeting Histone-Modifying PROTEIN METHYLTRANSFERASE4b. AB - Oxidative stress is unavoidable for aerobic organisms. When abiotic and biotic stresses are encountered, oxidative damage could occur in cells. To avoid this damage, defense mechanisms must be timely and efficiently modulated. While the response to oxidative stress has been extensively studied in plants, little is known about how the activated response is switched off when oxidative stress is diminished. By studying Arabidopsis mutant paraquat tolerance3, we identified the genetic locus PARAQUAT TOLERANCE3 (PQT3) as a major negative regulator of oxidative stress tolerance. PQT3, encoding an E3 ubiquitin ligase, is rapidly down-regulated by oxidative stress. PQT3 has E3 ubiquitin ligase activity in ubiquitination assay. Subsequently, we identified PRMT4b as a PQT3-interacting protein. By histone methylation, PRMT4b upregulates the expression of APX1 and GPX1, encoding two key enzymes against oxidative stress. On the other hand, PRMT4b is recognized by PQT3 for targeted degradation via 26S proteasome. Therefore, we have identified PQT3 as an E3 ligase that acts as a negative regulator of activated response to oxidative stress and found that histone modification by PRMT4b at APX1 and GPX1 loci plays an important role in oxidative stress tolerance. PMID- 27676072 TI - Exploration of Friendship Experiences, before and after Illness Onset in Females with Anorexia Nervosa: A Qualitative Study. AB - BACKGROUND: Difficulties with social relationships have been implicated in both the development and maintenance of Anorexia Nervosa (AN) but the friendship experiences of individuals with AN have not been explored in depth. METHOD: Ten adults with AN took part in a semi-structured interview about their friendship experiences both before and since the onset of their illness. RESULTS: Five principle themes were identified through thematic analysis: Social Concern; Impact of AN; Social Connectedness; Inflexibility and Preferred Social Activity. Difficulties with friendship were present prior to the onset of AN in all cases, with participants experiencing anxiety in relation to various aspects of their friendships. Participants described mixed experiences of how their AN has affected their friendships but most participants described having less contact with their friends since becoming unwell. CONCLUSION: This research highlights the role that social difficulties may play in the development of AN, whilst also emphasising the importance of addressing problems with friendship in the course of inpatient treatment. PMID- 27676076 TI - Linear, Star, and Comb Oxidation-Responsive Polymers: Effect of Branching Degree and Topology on Aggregation and Responsiveness. AB - Families of amphiphilic oxidation-responsive polymers (poly(ethylene glycol) polysulfides) with different architectures (linear, 4, 6, and 8-armed stars and 10, 15, and 20-armed combs) and compositions (variable ethylene sulfide/propylene sulfide ratio) are prepared. In water, all the polymers assemble in spherical micelles, with critical micellar concentrations <0.01 mg mL-1 for all the branched polymers. Triple-detection gel permeation chromatography (GPC) and asymmetric field flow fractionation (AFFF) with dynamic and static light scattering detection, respectively, show an increasing compaction of the polymeric coil and a strong reduction of the aggregation number with increasing degree of branching. The key finding of this study is that the kinetics of the oxidative response sharply depend on the branching; in particular, it is highlighted that the degree of branching influences the lag time before a response can be observed rather than the speed of the response itself, a phenomenon that is attributed to a branching-dependent solubility of the oxidant in the polysulfide matrix. PMID- 27676075 TI - Flow Cytometric Methods for Indirect Analysis and Quantification of Gametogenesis in Chlamydomonas reinhardtii (Chlorophyceae). AB - Induction of sexual reproduction in the facultatively sexual Chlamydomonas reinhardtii is cued by depletion of nitrogen. We explore the capacity for indirect monitoring of population variation in the gametogenic process using flow cytometry. We describe a high-throughput method capable of identifying fluorescence, ploidy and scatter profiles that track vegetative cells entering and undergoing gametogenesis. We demonstrate for the first time, that very early and late growth phases reduce the capacity to distinguish putative gametes from vegetative cells based on scatter and fluorescence profiles, and that early/mid logarithmic cultures show the optimal distinction between vegetative cells and gamete scatter profiles. We argue that early/mid logarithmic cultures are valuable in such high throughput comparative approaches when investigating optimisation or quantification of gametogenesis based on scatter and fluorescence profiles. This approach provides new insights into the impact of culture conditions on gametogenesis, while documenting novel scatter and fluorescence profile shifts which typify the process. This method has potential applications to; enabling quick high-throughput monitoring, uses in increasing efficiency in the quantification of gametogenesis, as a method of comparing the switch between vegetative and gametic states across treatments, and as criteria for enrichment of gametic phenotypes in cell sorting assays. PMID- 27676078 TI - Degradation of tricyclazole: Effect of moisture, soil type, elevated carbon dioxide and Blue Green Algae (BGA). AB - Pesticide persistence and degradation in soil are influenced by factors like soil characteristics, light, moisture etc. Persistence of tricyclazole was studied under different soil moisture regimes viz., dry, field capacity and submerged in two different soil types viz., Inceptisol and Ultisol from Delhi and Karnataka, respectively. Tricyclazole dissipated faster in submerged (t1/2 160.22-177.05d) followed by field capacity (t1/2 167.17-188.07d) and dry (t1/2 300.91-334.35d) in both the soil types. Half-life of tricyclazole in Delhi field capacity soil amended with Blue Green Algae (BGA), was 150.5d as compared to 167.1d in unamended soil. In Karnataka soil amended with BGA the half-lives were 177.0d compared to 188.0d in unamended soil, indicating that BGA amendment enhanced the rate of dissipation of in both the selected soils. Tricyclazole was found to be stable in water over a pH range of 3-9, the half life in paddy field was 60.20d and 5.47d in paddy soil and paddy water, respectively. Statistical analysis and Duncan's Multiple Range Test (DMRT) revealed significant effect of moisture regime, organic matter and atmospheric CO2 level on dissipation of tricyclazole from soil and pH of water (at 95% confidence level p<0.0001). PMID- 27676077 TI - Extreme Wildlife Declines and Concurrent Increase in Livestock Numbers in Kenya: What Are the Causes? AB - There is growing evidence of escalating wildlife losses worldwide. Extreme wildlife losses have recently been documented for large parts of Africa, including western, Central and Eastern Africa. Here, we report extreme declines in wildlife and contemporaneous increase in livestock numbers in Kenya rangelands between 1977 and 2016. Our analysis uses systematic aerial monitoring survey data collected in rangelands that collectively cover 88% of Kenya's land surface. Our results show that wildlife numbers declined on average by 68% between 1977 and 2016. The magnitude of decline varied among species but was most extreme (72-88%) and now severely threatens the population viability and persistence of warthog, lesser kudu, Thomson's gazelle, eland, oryx, topi, hartebeest, impala, Grevy's zebra and waterbuck in Kenya's rangelands. The declines were widespread and occurred in most of the 21 rangeland counties. Likewise to wildlife, cattle numbers decreased (25.2%) but numbers of sheep and goats (76.3%), camels (13.1%) and donkeys (6.7%) evidently increased in the same period. As a result, livestock biomass was 8.1 times greater than that of wildlife in 2011-2013 compared to 3.5 times in 1977-1980. Most of Kenya's wildlife (ca. 30%) occurred in Narok County alone. The proportion of the total "national" wildlife population found in each county increased between 1977 and 2016 substantially only in Taita Taveta and Laikipia but marginally in Garissa and Wajir counties, largely reflecting greater wildlife losses elsewhere. The declines raise very grave concerns about the future of wildlife, the effectiveness of wildlife conservation policies, strategies and practices in Kenya. Causes of the wildlife declines include exponential human population growth, increasing livestock numbers, declining rainfall and a striking rise in temperatures but the fundamental cause seems to be policy, institutional and market failures. Accordingly, we thoroughly evaluate wildlife conservation policy in Kenya. We suggest policy, institutional and management interventions likely to succeed in reducing the declines and restoring rangeland health, most notably through strengthening and investing in community and private wildlife conservancies in the rangelands. PMID- 27676079 TI - External heating of electrical cables and auto-ignition investigation. AB - Electric cables are now extensively used for both residential and industrial applications. During more than twenty years, multi-scale approaches have been developed to study fire behavior of such cables that represents a serious challenge. Cables are rather complicated materials because they consist of an insulated part and jacket of polymeric materials. These polymeric materials can have various chemical structures, thicknesses and additives and generally have a char-forming tendency when exposed to heat source. In this work, two test methods are used for the characterization of cable pyrolysis and flammability. The first one permits the investigation of cable pyrolysis. A description of the cable mass loss is obtained, coupling an Arrhenius expression with a 1D thermal model of cables heating. Numerical results are successfully compared with experimental data obtained for two types of cable commonly used in French nuclear power plants. The second one is devoted to ignition investigations (spontaneous or piloted) of these cables. All these basic observations, measurements and modelling efforts are of major interest for a more comprehensive fire resistance evaluation of electric cables. PMID- 27676080 TI - Evaluation of a battery of marine species-based bioassays against raw and treated municipal wastewaters. AB - The present study evaluates a battery of marine species-based bioassays against chemically characterized municipal wastewater samples (raw and WWTP treated). We estimated Dunaliella tertiolecta growth rate inhibition (24-96h IC50 values), Artemia franciscana immobilization (24h LC50 values), mussel hemocytes viability and lipid peroxidation enhancement (in terms of neutral red retention assay/NRRT and malondialdehyde/MDA content, respectively) in influent- and WWTP effluent treated species. We found algal growth arrest and stimulation respectively, almost similar 24hLC50 values in Artemia sp., and significantly higher adverse effects (in terms of NRRT and MDA levels) in influent-treated mussel hemocytes. Furthermore, the estimation of hatchability, yolk-sac larvae mortality (24 120hLC50) and spinal deformities (SD) in sea bream Sparus aurata showed slight variations over time, with the lowest LC50 and SD50 (representing spinal deformities at 50% of yolk-sac larvae) values to be observed in influent-treated larvae at 120h. Data interpretation (both chemical and biological) revealed that toxic endpoints, such as NRRT50, 96hIC50Dun, 120hLC50Sparus and 120hSD50Sparus, significantly related to WWTP removal efficiency and further mediated by the presence of dominant compounds, such as As and Cr, could be used for identifying main components of toxicity in wastewaters. PMID- 27676082 TI - Shape Effects on Electronic States of Nanocrystals. AB - High-performance supercomputing and high-fidelity atomistic methods are used to study the shape effects on the single-particle electronic states of nanocrystals. We found that the shape can be used as an efficient way to control the electronic structures of the nanocrystals. Changing the shape is more flexible and provides more variety of electronic states than simply changing the size of the system. The special features of the electronic states achieved by different shapes of the nanocrystals can be used in various device applications. Simple rules are summarized to predict the electronic structure shape effects on similar nanocrystals. PMID- 27676081 TI - Citric Acid for Nocturnal Muscle Cramps. PMID- 27676083 TI - Test Pricing and Reimbursement in Genomic Medicine: Towards a General Strategy. AB - This paper aims to provide an overview of the rationale and basic principles guiding the governance of genomic testing services, to clarify their objectives, and allocate and define responsibilities among stakeholders in a health-care system, with a special focus on the EU countries. Particular attention is paid to issues pertaining to pricing and reimbursement policies, the availability of essential genomic tests which differs between various countries owing to differences in disease prevalence and public health relevance, the prescribing and use of genomic testing services according to existing or new guidelines, budgetary and fiscal control, the balance between price and access to innovative testing, monitoring and evaluation for cost-effectiveness and safety, and the development of research capacity. We conclude that addressing the specific items put forward in this article will help to create a robust policy in relation to pricing and reimbursement in genomic medicine. This will contribute to an effective and sustainable health-care system and will prove beneficial to the economy at large. PMID- 27676084 TI - Advances in the development and applications of organic-silica hybrid monoliths. AB - This review will concentrate on recent progress (since 2013) toward preparation of organic-silica hybrid monoliths and their latest applications as extraction and separation media largely focusing on capillary liquid chromatography and capillary electrochromatography. Main emphasis will be given to advancement of approaches relying on the sol-gel chemistry of tetra- and tri-alkoxysilanes, sol gel chemistry of alkoxysilanes and free-radical copolymerization with organic monomers, and free radical and ring-opening copolymerization of polyhedral oligomeric silsesquioxanes with organic monomers. Hybrid molecularly-imprinted polymer monoliths and hybrid monoliths made with non-silica-based precursors or in combination with metal alkoxides will be included as well. PMID- 27676085 TI - Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. AB - BACKGROUND/AIMS: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. METHODS: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 ug) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. RESULTS: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of >=30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. CONCLUSION: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD. PMID- 27676087 TI - Hydrogen-bonded polymer nanocomposites containing discrete layers of gold nanoparticles. AB - The ability to finely control the spatial location and relative concentration of a nanofiller within a polymer nanocomposite is desirable, especially when faced with fillers that are susceptible to aggregation. In the case of gold nanoparticles (AuNPs), spatial organization is of interest as it offers a means to harness optical and electrical properties, but well-defined placement of AuNPs within a polymer matrix is generally challenging because of phase separation. Here, we demonstrate for the first time the spray-assisted layer-by-layer assembly (LbL) of hydrogen-bonding polymer nanocomposites of poly(ethylene oxide) (PEO) and poly(methacrylic acid) (PMAA) containing discrete regions of AuNPs vertically positioned throughout the film structure. Analysis of the internal structure using cross-sectional transmission electron microscopy (TEM) imaging shows that the AuNP regions are clearly separated by "empty" regions of polymer with no drift or aggregation of the Au NPs during or after fabrication. A UV-vis spectroscopy study of the stimuli-responsive properties of the spray-assisted LbL nanocomposites shows the release of AuNPs as induced by elevating the environmental pH above the critical pH at which the PEO and PMAA hydrogen bonds are disrupted. We anticipate that this work enables the spatial organization of other nanofillers in stimuli-responsive hydrogen-bonding nanocomposites by spray assisted LbL assembly. PMID- 27676086 TI - Zwitterionic stealth peptide-capped 5-aminolevulinic acid prodrug nanoparticles for targeted photodynamic therapy. AB - 5-Aminolevulinic acid (ALA) is a FDA-approved photodynamic therapy (PDT) precursor of protoporphyrin IX (PpIX) used for treating various cancers. However, the internalization of ALA is a big challenge due to its hydrophilic nature and low specificity to cancer cells. In this work, ALA conjugated prodrug nanoparticles were prepared by conjugation of thiolated stealth peptide sequence CPPPPEKEKEKEKEKEDGR and hydrazone-containing ALA to gold nanoparticles (AuNPs). Remarkable anti-fouling ability of ALA prodrug nanoparticles in complex environment was achieved owing to the zwitterionic stealth peptide sequence EKEKEKEKEK. The release of ALA could be greatly accelerated upon incubation of ALA prodrug nanoparticles in lysosomal/endosomal pH (pH 5.5). Meanwhile, the cellular internalization could be greatly enhanced by RGD moieties. MTT results demonstrated that ALA prodrug nanoparticles exhibited better photodynamic cytotoxicity than free ALA after light irradiation, suggesting enhanced photodynamic therapeutic efficacy. PMID- 27676090 TI - Efficient Synthesis of Bibutenolide Derivatives through Oxidative Dimeric Cyclization-Coupling Reaction of 2,3-Allenoic Acids. PMID- 27676089 TI - A Cyclic Tetrapeptide ("Cyclodal") and Its Mirror-Image Isomer Are Both High Affinity MU Opioid Receptor Antagonists. AB - Head-to-tail cyclization of the MU opioid receptor (MOR) agonist [Dmt1]DALDA (H Dmt-d-Arg-Phe-Lys-NH2 (9; Dmt = 2',6'-dimethyltyrosine) resulted in a highly active, selective MOR antagonist, c[-d-Arg-Phe-Lys-Dmt-] (1) ("cyclodal"), with subnanomolar binding affinity. A docking study of cyclodal using the crystal structure of MOR in the inactive form showed a unique binding mode with the two basic residues of the ligand forming salt bridges with the Asp127 and Glu229 receptor residues. Cyclodal showed high plasma stability and was able to cross the blood-brain barrier to reverse morphine-induced, centrally mediated analgesia when given intravenously. Surprisingly, the mirror-image isomer (optical antipode) of cyclodal, c[-Arg-d-Phe-d-Lys-d-Dmt-] (2), also turned out to be a selective MOR antagonist with 1 nM binding affinity, and thus, these two compounds represent the first example of mirror image opioid receptor ligands with both optical antipodes having high binding affinity. Reduction of the Lys Dmt peptide bond in cyclodal resulted in an analogue, c[-d-Arg-Phe LysPsi[CH2NH]Dmt-] (8), with MOR agonist activity. PMID- 27676088 TI - Angiotensin-(1-7) Selectively Induces Relaxation and Modulates Endothelium Dependent Dilation in Mesenteric Arteries of Salt-Fed Rats. AB - This study investigated the acute effects of angiotensin-(1-7) and AVE0991 on active tone and vasodilator responses to bradykinin and acetylcholine in isolated mesenteric arteries from Sprague-Dawley rats fed a high-salt (HS; 4% NaCl) versus a normal salt (NS; 0.4% NaCl) diet. Angiotensin-(1-7) and AVE0991 elicited relaxation, and angiotensin-(1-7) unmasked vasodilator responses to bradykinin in arteries from HS-fed rats. These effects of angiotensin-(1-7) and AVE0991 were inhibited by endothelium removal, A779, PD123319, HOE140 and L-NAME. Angiotensin (1-7) also restored the acetylcholine-induced relaxation that was suppressed by the HS diet. Vasodilator responses to bradykinin and acetylcholine in the presence of angiotensin-(1-7) were mimicked by captopril and the AT2 receptor agonist CGP42112 in arteries from HS-fed rats. Thus, in contrast to salt-induced impairment of vascular relaxation in response to vasodilator stimuli, angiotensin (1-7) induces endothelium-dependent and NO-mediated relaxation, unmasks bradykinin responses via activation of mas and AT2 receptors, and restores acetylcholine-induced vasodilation in HS-fed rats. AT2 receptor activation and angiotensin-converting enzyme (ACE) inhibition shared the ability of angiotensin (1-7) to enhance bradykinin and acetylcholine responses in HS-fed rats. These findings suggest a therapeutic potential for mas and/or AT2 receptor activation and ACE inhibition in restoring endothelial function impaired by elevated dietary salt intake or other pathological conditions. PMID- 27676091 TI - Impact of caffeine in hepatitis C virus infection: a systematic review and meta analysis. AB - BACKGROUND/OBJECTIVES: Hepatitis C virus (HCV) infection is one of the most common causes of cirrhosis. Several studies have linked caffeine consumption to a lower degree of liver fibrosis and inflammation among patients with chronic HCV infection, but the results were inconsistent. This meta-analysis was carried out with the aim of assessing the impact of caffeine consumption among HCV-infected patients. PARTICIPANTS AND METHODS: A literature search was performed using MEDLINE and EMBASE from inception to January 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of advanced liver fibrosis or the risk of moderate to severe liver inflammation among HCV-infected patients who consumed caffeine on a regular basis versus those who did not were included. Pooled odds ratios (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse-variance method. RESULTS: Five studies were included in the fibrosis analysis. The pooled OR of advanced liver fibrosis in HCV-infected patients who consumed caffeine on a regular basis versus those who did not was 0.48 (95% CI, 0.30-0.76, I=52%). Three studies were included in the inflammation analysis. The pooled OR of moderate to severe histologic inflammation among HCV-infected patients who consumed caffeine on a regular basis versus those who did not was 0.61 (95% CI, 0.35-1.04, I=43%). CONCLUSION: Our study showed a decreased risk of advanced liver fibrosis and liver inflammation among HCV-infected patients who consumed caffeine on a regular basis. Whether consumption of caffeine plays a role in the management of HCV infection requires further investigations. PMID- 27676092 TI - Screening for colorectal cancer: the role of the primary care physician. AB - In recent years, the role of primary care physicians (PCPs) in the diagnosis and management of gastrointestinal disorders, including screening for colorectal cancer (CRC), has been recognized as very important. The available data indicate that PCPs are not adequately following CRC screening guidelines because a number of factors have been identified as significant barriers to the proper application of CRC screening guidelines. These factors include lack of time, patient reluctance, and challenges related to scheduling colonoscopy. Further positive engagement of PCPs with CRC screening is required to overcome these barriers and reach acceptable levels in screening rates. To meet the expectations of modern medicine, PCPs should not only be able to recommend occult blood testing or colonoscopy but also, under certain conditions, able to perform colonoscopy. In this review, the authors aim to provide the current knowledge of the role of PCPs in increasing the rate and successfully implementing a screening program for CRC by applying the relevant international guidelines. PMID- 27676094 TI - Substrate-Regulated Growth of Plasma-Polymerized Films on Carbide-Forming Metals. AB - Although plasma polymerization is traditionally considered as a substrate independent process, we present evidence that the propensity of a substrate to form carbide bonds regulates the growth mechanisms of plasma polymer (PP) films. The manner by which the first layers of PP films grow determines the adhesion and robustness of the film. Zirconium, titanium, and silicon substrates were used to study the early stages of PP film formation from a mixture of acetylene, nitrogen, and argon precursor gases. The correlation of initial growth mechanisms with the robustness of the films was evaluated through incubation of coated substrates in simulated body fluid (SBF) at 37 degrees for 2 months. It was demonstrated that the excellent zirconium/titanium-PP film adhesion is linked to the formation of metallic carbide and oxycarbide bonds during the initial stages of film formation, where a 2D-like, layer-by-layer (Frank-van der Merwe) manner of growth was observed. On the contrary, the lower propensity of the silicon surface to form carbides leads to a 3D, island-like (Volmer-Weber) growth mode that creates a sponge-like interphase near the substrate, resulting in inferior adhesion and poor film stability in SBF. Our findings shed light on the growth mechanisms of the first layers of PP films and challenge the property of substrate independence typically attributed to plasma polymerized coatings. PMID- 27676093 TI - A comparison of sedation with midazolam-ketamine versus propofol-fentanyl during endoscopy in children: a randomized trial. AB - PURPOSE: We aimed to compare the efficacy and safety of midazolam plus ketamine versus fentanyl plus propofol combination administered to children undergoing upper gastrointestinal endoscopy (UGE) and to determine the most appropriate sedation protocol. MATERIALS AND METHODS: This prospective, randomized, single blind study included patients between the ages of 4 and 17 years who underwent UGE for diagnostic purposes. Patients were divided randomly into groups A (midazolam-ketamine combination, n=119) and B (fentanyl plus propofol combination, n=119). The effectiveness of the sedation and complications during the procedure and recovery period were recorded. RESULTS: The processes started without an additional dose of the drug for 118 patients (99.1%) in group A and for 101 patients (84.8%) in group B (P=0.001). The average dose of ketamine administered to the patients in group A was 1.03+/-0.15 mg/kg and the average dose of propofol administered to the patients in group B was 1.46+/-0.55 mg/kg. None of the patients stopped the endoscopic procedure in group A, but one patient (0.8%) had to discontinue the endoscopic procedure in group B. 27 patients in group A (22.7%) and 41 patients (34.5%) in group B developed complications during the procedure (P=0.044). The rate of complications during the recovery of group A (110 patients, 92.4%) was significantly higher than that in group B (48 patients, 40.3%) (P=0.001). CONCLUSION: In children, UGE procedures can be quite comfortable when using the midazolam-ketamine combination. However, adverse effects related to ketamine were observed during recovery. PMID- 27676095 TI - Design and Synthesis of New Cell Penetrating Peptides: Diffusion and Distribution Inside the Cornea. AB - The role of cell penetrating peptides (CPPs) has been challenged in recent years for drug delivery to ocular tissues for the targeting of both anterior and posterior segments. The enhancement of trans-corneal transport for anterior segment targeting is a very important issue possibly leading to important outcomes on efficacy and to the opportunity of topical administration of molecules with unfavorable penetration properties. The aim of the present work was the design and synthesis of new CPPs, deriving from the structure of PEP-1 peptide. Synthesized peptides were labeled with 5-carboxyfluorescein (5-FAM), and their diffusion behavior and distribution inside the cornea were evaluated by a validated ex vivo model and a confocal microscopy approach. Newly synthesized peptides showed similar corneal permeation profiles as PEP-1 (Papp = 0.75 +/- 0.56 * 10-6 cm/s), about 2.6-fold higher than 5-FAM (Papp = 0.29 +/- 0.08 * 10-6 cm/s) despite the higher molecular weight. Confocal microscopy experiments highlighted the tendency of PEP-1 and its derived peptides to localize in the intercellular space and/or in the plasma membrane. Noteworthy, using penetratin as positive control, a higher trans-corneal permeation (Papp = 6.18 +/- 1.46 * 10 6 cm/s) was evidenced together with a diffusion by intracellular route and a different accumulation between wings and basal epithelial cells, probably depending on the stage of cell development. Finally, PEP-1 and pep-7 proved to be safe and well tolerated when tested on human conjuctival cell line. PMID- 27676097 TI - Direct Determination of Contaminants and Major and Minor Nutrients in Solid Fertilizers Using Laser-Induced Breakdown Spectroscopy (LIBS). AB - Contaminants (Cd, Cr, and Pb) as well as minor (B, Cu, Mn, Na, and Zn) and major (Ca and Mg) elements were directly determined in solid fertilizer samples using laser-induced breakdown spectroscopy (LIBS). Factorial designs were used to define the most appropriate LIBS parameters and pellet pressure on solid fertilizers. Emission lines for all of the analytes were collected and employed 12 signal normalization modes. The best results were obtained using a laser energy of 75 mJ, a spot size of 50 MUm, a pressure of 10 t/in., and a delay of 2.0 MUs. Good correlation was obtained between the calibration model's prediction using the proposed LIBS method and the reference values obtained with ICP-OES. The limits of detection (LOD) for the proposed method varied from 2 mg/kg (for Cd) to 1% (for Zn). PMID- 27676098 TI - Postgraduate students' perceptions of high-quality precepting in critical care nursing. AB - Education of critical care nurses in Norway consists of equal parts clinical practice and theoretical education. The purpose of this study was to investigate postgraduate students' perceptions of the one-on-one, bedside precepting they received during their critical care education. Two focus group interviews with students at a Norwegian university college were conducted, and a thematic cross case analysis was done. The interviewees characterized high-quality precepting as precepting where proper precepting strategies are applied, right priorities in precepting are made, the preceptor possesses desirable qualities, and there is a good preceptor-student relationship. High-quality precepting of postgraduate critical care nursing students should reflect the complexity of the profession, emphasizing both practical and theoretical knowledge. Strategies resembling both the master-apprentice model and the reflective counselling model should be applied. Postgraduate students' characterizations of high-quality precepting should be taken into consideration when preparing critical care nurses to undertake precepting within clinical education. Attention should be paid to the difference between undergraduate students and postgraduate students educating for a speciality. PMID- 27676096 TI - Evaluation of Chromane-Based Bryostatin Analogues Prepared via Hydrogen-Mediated C-C Bond Formation: Potency Does Not Confer Bryostatin-like Biology. AB - The synthesis and biological evaluation of chromane-containing bryostatin analogues WN-2-WN-7 and the previously reported salicylate-based analogue WN-8 are described. Analogues WN-2-WN-7 are prepared through convergent assembly of the chromane-containing fragment B-I with the "binding domain" fragment A-I or its C26-des-methyl congener, fragment A-II. The synthesis of fragment B-I features enantioselective double C-H allylation of 1,3-propanediol to form the C2 symmetric diol 3 and Heck cyclization of bromo-diene 5 to form the chromane core. The synthesis of salicylate WN-8 is accomplished through the union of fragments A III and B-II. The highest binding affinities for PKCalpha are observed for the C26-des-methyl analogues WN-3 (Ki = 63.9 nM) and WN-7 (Ki = 63.1 nM). All analogues, WN-2-WN-8, inhibited growth of Toledo cells, with the most potent analogue being WN-7. This response, however, does not distinguish between phorbol ester-like and bryostatin-like behavior. In contrast, while many of the analogues contain a conserved C-ring in the binding domain and other features common to analogues with bryostatin-like properties, all analogues evaluated in the U937 proliferation and cell attachment assays displayed phorbol ester-like and/or toxic behavior, including WN-8, for which "bryostatin-like PKC modulatory activities" previously was suggested solely on the basis of PKC binding. These results underscore the importance of considering downstream biological effects, as tumor suppression cannot be inferred from potent PKC binding. PMID- 27676099 TI - Upregulation of miR-98 Inhibits Apoptosis in Cartilage Cells in Osteoarthritis. AB - OBJECTIVE: We aimed to investigate the effects of microRNA-98 (miR-98) on apoptosis in cartilage cells of osteoarthritis (OA) patients. METHODS: Knee cartilage tissue samples were collected from 31 OA patients, 21 autopsies, and 26 amputation patients due to trauma. The clinicopathological data were recorded. Quantitative real-time polymerase chain reaction was performed to compare the miR 98 expression levels from cartilage cells obtained from the OA and non-OA patients. Clinicopathological characteristics of the patients were also analyzed. Primary chondrocytes were separated from cartilage tissues and transfected with plasmids or siRNA to overexpress or inhibit miR-98. Annexin V-PI double staining and TUNEL assays were used to examine apoptosis in the primary chondrocytes after transfection. Finally, a rat OA model was used to confirm the effects of miR-98 on apoptosis in cartilage cells in vivo. RESULTS: Compared with the normal cartilage tissues, miR-98 expression was reduced in the OA cartilage tissues (p < 0.01). The miR-98 expression levels were also significantly correlated with the OA stage (p < 0.05). In vitro, transfection with the miR-98 inhibitor increased apoptosis in the cartilage cells (p < 0.05), and transfection with a miR-98 mimic inhibited apoptosis in cartilage cells (p < 0.05). In the OA rat model, exogenous injection of the miR-98 mimic inhibited apoptosis in the rat cartilage cells thus alleviating OA. CONCLUSION: MiR-98 expression is reduced in the cartilage cells of OA patients and the overexpression of miR-98 inhibits cartilage cell apoptosis, while inhibition of microRNA-98 leads to cartilage cell apoptosis. These findings provide a theoretical basis for the development of novel targeted therapies for OA. PMID- 27676101 TI - Comparison of Salter osteotomy and Tonnis lateral acetabuloplasty with simultaneous open reduction for the treatment of developmental dysplasia of the hip: midterm results. AB - The aim of this study was to compare the midterm clinical and radiological outcomes of the Salter osteotomy (SO) and Tonnis lateral acetabuloplasty (TLA) with concomitant open reduction for the treatment of developmental dysplasia of the hip. Twenty-five hips of 20 patients who underwent SO with open reduction and 26 hips of 23 patients who underwent TLA with open reduction were evaluated retrospectively. The average age of the patients at the time of the operation was 35.6 months in the SO and 36.6 months in the TLA group, without a statistically significant difference (P=0.836). The average follow-up times in the SO and TLA groups were 59.9 and 54.8 months, respectively (P=0.397). Preoperative (40.6 degrees in the SO vs. 42.2 degrees in the TLA, P=0.451) and last follow-up acetabular index (12 degrees in the SO vs. 14 degrees in the TLA, P=0.227) and center-edge angle measurements (30 degrees in the SO vs. 26 degrees in the TLA, P=0.069) did not show a statistically significant difference between the SO and TLA groups; however, early postoperative acetabular index improvement was better in the TLA group than in the SO group (21.2 degrees in the SO vs. 17.2 degrees in the TLA, P=0.014). According to the Severin grading system, both groups showed a similar number of good outcomes without a statistically significant difference (P=0.936). Clinical assessment on the basis of McKay's criteria showed similar good and excellent outcomes (P=0.936). Both osteotomy techniques showed similar satisfactory outcomes for the treatment of DDH in patients older than 18 months of age. PMID- 27676100 TI - DAT1 methylation is associated with methylphenidate response on oppositional and hyperactive-impulsive symptoms in children and adolescents with ADHD. AB - OBJECTIVES: To examine the association of the DNA methylation of DAT1 and DRD4 gene with methylphenidate (MPH) response in attention deficit hyperactivity disorder (ADHD). METHODS: One hundred and eleven DSM-IV defined ADHD Chinese Han children were recruited. Inattention, hyperactivity-impulsivity and oppositional symptoms were evaluated by the Swanson, Nolan and Pelham-IV-parent rating scale (SNAP-IV-P) at baseline and 6 weeks after MPH treatment. DNA methylation of CpG sites in the promoter sequences of DAT1 and DRD4 was examined for association with treatment response. RESULTS: Greater improvement on the SNAP-IV-P total score and percentage change from baseline score were both significantly correlated with DAT1 methylation (rho =-0.222, P = .019 and rho = -0.203, P = .032, respectively). A secondary analysis demonstrated that the effect of DAT1 methylation on symptom response was primarily related to the percentage change in oppositional symptoms (rho = -0.242; P = .012), with a smaller significant effect on hyperactivity-impulsivity (rho = -0.192; P = .045). No significant correlation was found between the treatment effect on inattention and DAT1 methylation (rho = -0.101; P = .292). No significant correlation was observed between mean DRD4 methylation and measures of treatment outcome or baseline symptoms. CONCLUSIONS: Our findings provide initial evidence for the involvement of the epigenetic alterations of DAT1 in modulating the response to MPH treatment in ADHD, primarily on oppositional and hyperactive-impulsive symptoms. PMID- 27676102 TI - Pediatric pelvic pyomyositis: initial MRI can be misleading. AB - Pelvic pyomyositis is an infection of the skeletal muscles around the hip joint. Fever, hip pain, limp, and leukocytosis are common; however, the clinical picture is often vague. MRI is the current gold-standard imaging for pyomyositis. No studies in the current literature have reported an unremarkable initial MRI in a patient with symptomatic pyomyositis. An adolescent female presented with symptomatic pelvic pyomyositis, but admission MRI was normal. A follow-up MRI indicated development of pelvic pyomyositis. The patient was successfully managed nonoperatively. The initial MRI in pyomyositis can be misleading. Patients should be admitted and MRI should be repeated, as indicated clinically. PMID- 27676105 TI - Transplantation of Adipose-Derived Stem Cell Sheet Attenuates Adverse Cardiac Remodeling in Acute Myocardial Infarction. AB - Adipose-derived stem cell (ADSC) transplantation has been proposed to improve cardiac function and acute myocardial infarction (AMI). Recently, cell sheet technology has been investigated for its potential applicability in cardiac injury. However, a detailed comparison of the functional recovery in the injured myocardium between cell sheets and conventional cell injection has not been adequately examined. ADSCs were isolated from the inguinal fat tissue of ICR mice. Three groups of AMI induction only (sham), intramyocardial injection of ADSCs (imADSC), and ADSC sheet transplantation (shADSC) were compared by using rat AMI models. Engraftment of ADSCs was better sustained through 28 days in the shADSC group compared with the imADSC group. Ejection fraction was improved in both imADSC and shADSC groups compared with the sham group. Ventricular wall thickness in the infarct zone was higher in the shADSC group compared with both imADSC and sham groups. Growth factor and cytokine expression in the implanted heart tissue were higher in the shADSC group compared with both imADSC and sham groups. Furthermore, only the shADSC group showed donor-derived vessels at the peri-infarct zone. Taken together, these results indicate that, although shADSC resulted in a similar improvement in left ventricular systolic function, it significantly promoted cellular engraftment and upregulated growth factor and cytokine expression, and, ultimately, attenuated adverse cardiac remodeling in rat AMI models compared with imADSC. PMID- 27676103 TI - Effect of Secreted Molecules of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells on Acute Hepatic Failure Model. AB - Adult tissue-derived mesenchymal stem cells (MSCs) show tremendous promise for a wide array of therapeutic applications predominantly through paracrine activity. Recent reports showed that human embryonic stem cell (ESC)-derived MSCs are an alternative for regenerative cellular therapy due to manufacturing large quantities of MSCs from a single donor. However, no study has been reported to uncover the secretome of human ESC-MSCs as treatment of an acute liver failure (ALF) mouse model. We demonstrated that human ESC-MSCs showed similar morphology and cell surface markers compared with bone marrow-derived MSCs. ESC-MSCs exhibited a higher growth rate during early in vitro expansion, along with adipogenic and osteogenic differentiation potential. Treatment with ESC-MSC conditioned medium (CM) led to statistically significant enhancement of primary hepatocyte viability and increased immunomodulatory interleukin-10 secretion from lipopolysaccharide-induced human blood mononuclear cells. Analysis of the MSCs secretome by a protein array screen showed an association between higher frequencies of secretory proteins such as vascular endothelial growth factor (VEGF) and regulation of cell proliferation, cell migration, the development process, immune system process, and apoptosis. In this thioacetamide-induced mouse model of acute liver injury, we observed that systemic infusion of VEGF led to significant survival. These data have provided the first experimental evidence of the therapeutic potential of human ESC-MSC-derived molecules. These molecules show trophic support to hepatocytes, which potentially creates new avenues for the treatment of ALF, as an inflammatory condition. PMID- 27676107 TI - Skin Care Special Issue: Diaper Dermatitis and Extremely Preterm Infant Skin Care. PMID- 27676108 TI - Issues in Newborn Skin Care. PMID- 27676106 TI - Protective Effects of Gallic Acid Against NiSO4-Induced Toxicity Through Down Regulation of the Ras/ERK Signaling Pathway in Beas-2B Cells. AB - BACKGROUND This study aimed to explore the preventive effects of gallic acid (GA) on the toxicity induced by NiSO4 in Beas-2B cells. MATERIAL AND METHODS Beas-2B cell viability was measured by MTT assay. The degree of oxidative stress was detected by measuring the levels of reactive oxygen species (ROS) and lipid peroxide (LPO). The rate of apoptosis was measured by flow cytometry. Ras/ERK related protein levels were analyzed by Western blot analysis, which including Ras, ERK, c-Myc, PARP, and PARP cleavage. RESULTS MTT assay showed that NiSO4 induced cytotoxicity, while GA had a protective role against toxicity. Additionally, GA could reduce the apoptotic cell number and the level of ROS in Beas-2B cells induced by NiSO4. Western blot analysis demonstrated that NiSO4 could up-regulate the related protein in the Ras/ERK signaling pathway. Furthermore, we observed that GA could alleviate the toxicity of NiSO4 through regulating protein changes in the Ras/ERK signaling pathway. CONCLUSIONS Preventive effects of GA on NiSO4-induced cytotoxicity in Beas-2B cells may be through the Ras/ERK signaling pathways. PMID- 27676109 TI - Bathing and Beyond: Current Bathing Controversies for Newborn Infants. AB - BACKGROUND: Bathing the newborn infant is controversial, ranging from how and when to give the newborn their first bath, whether to bathe newborns at all in the initial days of life, and how to approach bathing the hospitalized premature and full-term infant in the neonatal intensive care unit (NICU). PURPOSE: To review relevant literature about bathing newborn infants, as well as examine the controversies about bathing NICU patients including the use of daily chlorhexidine gluconate (CHG) baths. FINDINGS: Despite studies showing that temperature can be maintained when the first bath was at 1 hour after delivery, there are benefits from delaying the bath including improved breastfeeding. Tub or immersion bathing improves temperature, and is less stressful. It is not necessary to bathe infants every day, and premature infants can be bathed as little as every 4 days without an increase in skin colonization. No differences have been reported in skin parameters such as pH, transepidermal water loss, and stratum corneum hydration whether the first and subsequent baths are given using water alone or water and a mild baby cleanser. Concerns about systemic absorption suggests caution about widespread practice of daily CHG bathing in the NICU until it is known whether CHG crosses the blood-brain barrier, particularly in premature infants. IMPLICATIONS FOR PRACTICE AND RESEARCH: Research regarding bathing practices for NICU patients should be evidence-based whenever possible, such as the benefits of immersion bathing. More evidence about the risks and benefits of daily CHG bathing is needed before this practice is widely disseminated. PMID- 27676110 TI - Diaper Dermatitis: What Do We Do Next? AB - Diaper dermatitis is a major issue among hospitalized infants, leading to increased medical costs, pain, risk for infection, and distress among patients and caregivers. An evidence-based algorithm for prevention and treatment of diaper dermatitis was developed and introduced in a level IV neonatal intensive care unit (NICU). Two cases are discussed as examples of severe diaper dermatitis. The first case demonstrates the final case of severe diaper dermatitis since the introduction of the algorithm. The second case demonstrates a less severe, but equally frustrating, case of diaper dermatitis that occurred after the practice of using the algorithm was established. The need for consistency in the prevention and treatment of diaper dermatitis is paramount to providing quality care. There are a number of points within the bedside care regimen where breakdown in consistency occurs. The adherence to consistent and evidence-based treatment regimens has the potential to decrease the incidence and severity of diaper dermatitis in high-risk hospitalized infants. Initiation of an evidence-based algorithm to assist in the prevention and treatment of diaper dermatitis can be supported by data of the number of cases of diaper dermatitis collected before and after implementing the algorithm. The information can further assist in continued education and pursuance of investigation of other major skin injuries in NICU patients. The importance surrounding infant skin care and building awareness surrounding all of the facets of skin care in this vulnerable population demonstrate the benefits to quality outcomes and care. PMID- 27676111 TI - Extremely Preterm Infant Skin Care: A Transformation of Practice Aimed to Prevent Harm. AB - BACKGROUND: The skin of extremely preterm infants is underdeveloped and has poor barrier function. Skin maintenance interventions initiated in the neonatal intensive care unit (NICU) have immediate and lifelong implications when the potential for infection, allergen sensitization, and altered aesthetic outcomes are considered. In addition, the high-level medical needs of extremely preterm infants demand skin-level medical interventions that too often result in unintended skin harm. PURPOSE: We describe the use of a harm prevention, or consequence-centered, approach to skin care, which facilitates safer practice for extremely premature infants. METHOD: Neonatal and pediatric Advanced Practice Registered Nurses (APRN) came together for monthly meetings to review the evidence around best skin care practices for extremely preterm infants, with an emphasis on reduction of skin harm. Findings were focused on the population of interest and clinical implementation strategies. FINDINGS: Skin care for extremely preterm infants remains overlooked by current literature. However, clinical practice pearls were extracted and applied in a manner that promotes safer skin care practices in the NICU. IMPLICATIONS FOR PRACTICE: Gentle adhesives, such as silicone tapes and hydrogel-backed electrodes, can help to reduce medical adhesive-related skin injuries. Diaper wipes are not appropriate for use among extremely preterm infants, as many ingredients may contain potential allergens. Skin cleansers should be pH neutral to the skin and the prophylactic use of petrolatum-based emollients should be avoided. IMPLICATIONS FOR RESEARCH: Further exploration and understanding of skin care practices that examine issues of true risk versus hypothetical risk of harm. PMID- 27676112 TI - Infant Skin Care Products: What Are the Issues? AB - BACKGROUND: Infant skin is susceptible to dryness and irritation from external factors, including topical skin care products not formulated for the infant's skin. This may increase the risk of contact dermatitis. Parents frequently express concern regarding potential harm from ingredients in skin care products and seek information. This is complicated by several skin care myths. PURPOSE: The purpose of this literature review was to provide evidence-based information to educate parents on the use of products for preterm and term infants. SEARCH STRATEGY: Multiple searches using PubMed were conducted including the search terms "infant skin care," "infant products," "infant bath," "emollients," "diaper skin care," and "diaper wipes." Reference lists of comprehensive reviews were also scanned. Google searches were used to assess consumer information, product information, and regulatory guidelines. FINDINGS: There is little scientific evidence to support safety of natural/organic products on infant skin. Raw materials originate from different sources, complicating testing and comparisons of ingredients. Research shows that cleansers formulated for infant skin do not weaken the skin barrier the way harsher soaps and detergents can. Oils with the lowest oleic acid content provide a lower risk of irritant contact dermatitis. IMPLICATIONS FOR PRACTICE: Nurses must be informed about natural and organic products, preservatives, and fragrances and know the definition of commonly used marketing terms. IMPLICATIONS FOR RESEARCH: Decisions regarding the use of infant products in preterm and term infants should be evidence based. More research is needed to support claims regarding the safety of products used on infant skin. PMID- 27676113 TI - Skin Rounds: A Quality Improvement Approach to Enhance Skin Care in the Neonatal Intensive Care Unit. AB - BACKGROUND: Skin injuries are common among neonatal intensive care unit (NICU) patients and may lead to significant complications. Standardized methods of preventing, detecting, and treating skin injuries are needed. PURPOSE: The aim of this project was to standardize the assessment, documentation, and tracking of skin injuries among hospitalized neonatal patients and to determine the incidence of pressure ulcers in this patient population. METHODS: (1) Creation of an interdisciplinary skin team to identify skin injuries through weekly skin rounds. (2) Assessment of all patients at least twice daily for the presence of skin injuries. Interventions were implemented upon identification of a skin injury. Pressure ulcers of Stage II or more were further assessed by wound/ostomy nurses. FINDINGS: A total of 2299 NICU patients were hospitalized and assessed between July 2011 and December 2015. After the initiation of skin rounds, the baseline incidence of pressure ulcers increased from 0.49 per 1000 patient days to 4.6 per 1000 patient days, reflecting an improvement in detection and reporting. The most common skin injuries detected included erythema, skin tears, and ecchymosis; the most common cause of injuries was medical devices. IMPLICATIONS FOR PRACTICE: A dedicated skin team can improve the detection and reporting of skin injuries among NICU patients. Determination of the incidence of pressure ulcers in this population is critical to develop targeted interventions. IMPLICATIONS FOR RESEARCH: Further research is needed to determine the most effective interventions to prevent and treat skin injuries among hospitalized neonates. PMID- 27676114 TI - Correction: Allosteric signalling in the outer membrane translocation domain of PapC usher. PMID- 27676115 TI - Pregnant women with substance use disorders: The intersection of history, ethics, and advocacy. AB - Pregnant women with substance use disorders face many obstacles, including obtaining evidence-based treatment and care. This article (1) briefly reviews the history of pregnant women in clinical trials and substance use disorders treatment research; (2) identifies current ethical issues facing researchers studying pregnant women with substance use disorders; (3) presents and describes an ethical framework to utilize; and (4) identifies future directions needed to develop appropriate research and treatment policies and practices. Current research is not providing enough information to clinicians, policy-makers, and the public about maternal and child health and substance use disorders, and the data will not be sufficient to offer maximum benefit until protocols are changed. PMID- 27676116 TI - Pistacia lentiscus fruit oil reduces oxidative stress in human skin explants caused by hydrogen peroxide. AB - We investigated the efficacy of Pistacia lentiscus fruit oil (PLFO) for protecting human skin from damage due to oxidative stress. PLFO contains natural antioxidants including polyphenols, sterols and tocopherols. We compared the antioxidant potential of PLFO with extra virgin olive oil (EVOO). Explants of healthy adult human skin were grown in culture with either PLFO or EVOO before adding hydrogen peroxide (H2O2). We also used cultured skin explants to investigate the effects of PLFO on lipid oxidation and depletion of endogenous antioxidant defense enzymes including glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) one day after 2 h exposure to H2O2. We found that PLFO scavenged radicals and protected skin against oxidative injury. PLFO exhibited greater antioxidant and free radical scavenging activity than EVOO. Skin explants treated with PLFO inhibited H2O2 induced MDA formation by inhibition of lipid oxidation. In addition, the oil inhibited H2O2 induced depletion of antioxidant defense enzymes including GPx, SOD and CAT. We found that treatment with PLFO repaired skin damage owing to its antioxidant properties. PMID- 27676117 TI - Miniperc vs Shockwave Lithotripsy for Average-Sized, Radiopaque Lower Pole Calculi: A Prospective Randomized Study. AB - INTRODUCTION: To detect safety and feasibility of miniperc and extracorporeal shockwave lithotripsy (SWL) for treatment of average-sized (1-2 cm), radiopaque lower pole calculi in a prospective randomized manner. PATIENTS AND METHODS: In the period from January 2014 to June 2015, 150 patients were attached to this study with single lower pole radiopaque stone ranging from 10 to 20 mm. Patients were divided randomly into two groups using computer-generated randomization in an equal manner. First group patients were subjected to miniperc procedure, while second group patients underwent SWL. Patient's characters, stones' characters, fluoroscopic time, operative time, blood transfusion, hospital stay, retreatment, auxiliary procedure (AP), and complications using modified Clavien grading are tabulated and analyzed. RESULTS: This study included two equal groups with 75 patients in each group. With regard to age (37.75 +/- 11.25 vs 40.55 +/- 10.55), body mass index (26.92 +/- 2.26 vs 27.29 +/- 2.87), and stone size (1.55 +/- 0.28 vs 1.57 +/- 0.26), there was no significant statistical difference in both groups. Stone-free rate (SFR) (76% vs 96%), operative time (44.81 +/- 7.06 vs 93.37 +/- 12.29 minutes), fluoroscopy time (53 +/- 2.45 vs 180 +/- 7.31 seconds), hospital stay (5.72 +/- 1.01 vs 45.19 +/- 8.48 hour), and blood transfusion were significantly more in the miniperc group. Retreatment rate (45.3% vs 2.7%) and AP (24% vs 4%) were significantly greater in the SWL group. CONCLUSION: SWL is less invasive than percutaneous stone removal, but it is also less effective for lower pole radiopaque calculi. Miniperc has better SFR and lower auxiliary and retreatment rates; however, it resulted in more drawbacks. PMID- 27676118 TI - Pooled Analysis of the Effects of Conjugated Estrogens/Bazedoxifene on Vasomotor Symptoms in the Selective Estrogens, Menopause, and Response to Therapy Trials. AB - OBJECTIVES: Conjugated estrogens/bazedoxifene (CE/BZA) reduced menopause-related hot flashes (HFs) in the Selective estrogens, Menopause, And Response to Therapy (SMART) trials. This post hoc pooled analysis of SMART-1 and -2 further characterized effects of CE/BZA on HFs in the overall population and patient subgroups. METHODS: Data from two randomized, double-blind, placebo- and active controlled, phase 3 studies were pooled for nonhysterectomized postmenopausal women with moderate/severe HFs given CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, or placebo for 12 weeks. HF frequency and severity were assessed by daily diary. RESULTS: The pooled analysis included 403 participants. At 12 weeks, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg significantly (all p < 0.001) decreased moderate/severe HF frequency versus placebo (-7.9, -8.2, -4.1), reduced adjusted average daily HF severity score versus placebo (-1.0, -1.3, -0.3), increased the percentage of women who had a >=50% (81.2%,87.1%, 50.6%) and >=75% (62.4%, 74.8%, 26.4%) reduction from baseline in daily frequency of moderate/severe HFs, increased the percentage with >=50% (38.3%, 58.1%, 11.0%) and >=75% (24.2%, 38.1%, 5.5%) reductions in average daily HF severity score, and improved MENQOL vasomotor function versus placebo (adjusted mean change-3.08, -3.69, -1.37). CE/BZA was significantly more effective than placebo irrespective of time since menopause, with some evidence of a lower placebo response in women in later menopause (>5 years) versus early menopause (<=5 years). CONCLUSIONS: CE/BZA effectively reduces moderate/severe HFs in postmenopausal women. NCT#'s: NCT00675688; NCT00234819. PMID- 27676120 TI - Therapeutic Hypothermia During Neonatal Transport: Active Cooling Helps Reach the Target. AB - Perinatal hypoxic ischemic encephalopathy (HIE) can lead to severe neurodevelopmental outcome and death. Therapeutic hypothermia is neuroprotective for infants with moderate-to-severe HIE. However, therapeutic hypothermia is only offered at high-level regional neonatal intensive care units (NICUs), necessitating the need to transport sick infants to referral centers. The goal of this study was to evaluate whether active cooling on transport is more effective than passive cooling in achieving temperatures in the treatment target range (33 degrees C-34 degrees C) on arrival to the Texas Children's Hospital (TCH) NICU. This was a retrospective quasi-experimental study of 42 infants who were transported to TCH for treatment of perinatal HIE between August 2012 and April 2016. Active cooling using a continuous core temperature servo-controlled cooling device (CritiCool) began in January 2014; before that, passive cooling on transport was used. Passive cooling was initiated by turning off external heating devices. Fourteen infants received active cooling, and 28 were passively cooled. Demographic data, gestational age at birth, birth weight, and Sarnat stage were not different between groups. Although TCH arrival temperatures were not different between the groups (p = 0.841), there was greater variability of temperatures in the passively cooled group (p = 0.001). More actively versus passively cooled patients arrived at the cooling center within the goal temperature range (79% vs. 25%, p = 0.003). After controlling for multiple variables, active cooling was a significant independent predictor for arriving at the cooling center within the goal temperature range. Active cooling during transport of infants with moderate-to-severe HIE was more effective than passive cooling in achieving the target goal temperature range on arrival at the cooling center. If cooling is being considered during transport, we suggest that active servo-controlled therapeutic hypothermia be used. PMID- 27676119 TI - Delirium and mental health history as predictors of aggression in individuals with dementia in inpatient settings. AB - OBJECTIVES: Aggressive behaviors by patients with dementia present risk to health care workers and patients. An information processing model, developed to study aggressive behaviors among children, was applied to study aggression among older hospital patients with dementia. Hypotheses were that delirium and mental health or depression history, would relate to increased risk of aggressive behaviors. METHOD: Electronic medical records were sampled for one year (n = 5008) and screened using the EMERSE search engine and hand review for dementia (n = 505) and aggressive behavior in individuals with dementia (n = 121). Records were reviewed for mental health history and presence of delirium. RESULTS: Regression analyses found interaction effects representing delirium and mental health or depression history associated with greater risk of aggressive behavior. Significant main effects were found for both dementia and mental health or depression history. Of the lowest risk group, 12% of patients exhibited aggression compared to 24%-35% of those with delirium, mental health or depression history, or the combination of these risk factors. CONCLUSION: Delirium is the leading correlate of aggressive behaviors in hospitalized patients with dementia, and delirium or history of mental health diagnosis may lead to increased risk of aggressive behaviors in this setting. PMID- 27676122 TI - Two-photon microscopy for intracutaneous imaging of stem cell activity in mice. AB - The adult skin is a typical example of a highly regenerative tissue. Terminally differentiated keratinocytes are shed from the external layers of the epidermis or extruded from the skin as part of the growing hair shaft on a daily basis. These are effectively replenished through the activity of skin-resident stem cells. Precise regulation of stem cell activity is critical for normal skin homoeostasis or wound healing and irregular stem cell proliferation or differentiation can lead to skin disease. The scarcity and dynamic nature of stem cells presents a major challenge for elucidating their mechanism of action. To address this, we have recently established a system for visualizing stem cell activity, in real time or long term, in the intact skin of live mice using two photon microscopy. The purpose of this review was to provide essential information to researchers who wish to incorporate two-photon microscopy and live imaging into their experimental toolbox for studying aspects of skin and stem biology in the mouse model. We discuss fundamental principles of the method, instrumentation and basic experimental approaches to interrogate stem cell activity in the interfollicular epidermis and hair follicle. PMID- 27676121 TI - Determination of local chromatin composition by CasID. AB - Chromatin structure and function are determined by a plethora of proteins whose genome-wide distribution is typically assessed by immunoprecipitation (ChIP). Here, we developed a novel tool to investigate the local chromatin environment at specific DNA sequences. We combined the programmable DNA binding of dCas9 with the promiscuous biotin ligase BirA* (CasID) to biotinylate proteins in the direct vicinity of specific loci. Subsequent streptavidin-mediated precipitation and mass spectrometry identified both known and previously unknown chromatin factors associated with repetitive telomeric, major satellite and minor satellite DNA. With super-resolution microscopy, we confirmed the localization of the putative transcription factor ZNF512 at chromocenters. The versatility of CasID facilitates the systematic elucidation of functional protein complexes and locus specific chromatin composition. PMID- 27676123 TI - Programming temporal shapeshifting. AB - Shapeshifting enables a wide range of engineering and biomedical applications, but until now transformations have required external triggers. This prerequisite limits viability in closed or inert systems and puts forward the challenge of developing materials with intrinsically encoded shape evolution. Herein we demonstrate programmable shape-memory materials that perform a sequence of encoded actuations under constant environment conditions without using an external trigger. We employ dual network hydrogels: in the first network, covalent crosslinks are introduced for elastic energy storage, and in the second one, temporary hydrogen-bonds regulate the energy release rate. Through strain induced and time-dependent reorganization of the reversible hydrogen-bonds, this dual network allows for encoding both the rate and pathway of shape transformations on timescales from seconds to hours. This generic mechanism for programming trigger-free shapeshifting opens new ways to design autonomous actuators, drug-release systems and active implants. PMID- 27676124 TI - Cognition, Health Literacy, and Actual and Perceived Medicare Knowledge Among Inner-City Medicare Beneficiaries. AB - Poor Medicare knowledge is associated with worse health outcomes, especially in low-income patients. We examined the association of health literacy and cognition with actual and perceived Medicare knowledge in a sample of inner-city older adults. We conducted a cross-sectional analysis of data on 336 adults ages 65 years and older with Medicare coverage recruited from senior centers and low income housing facilities in Manhattan, New York. Actual Medicare knowledge was determined by a summary score of 9 true/false questions about the Medicare program and perceived Medicare knowledge with a single item. Validated measures were used to assess health literacy and general cognition. Among respondents, 63.1% had high actual Medicare knowledge, and 36.0% believed that they knew what they needed to know about Medicare. Actual and perceived Medicare knowledge were poorly correlated (r = -.01, p > .05). In multivariable models, low health literacy was significantly associated with actual Medicare knowledge (beta = 8.30, SE = 2.71, p < .01) but not perceived Medicare knowledge (beta = 0.37, SE = 0.22, p = .09). Individuals with low health literacy were more likely to perceive their Medicare knowledge as adequate when actual Medicare knowledge was low (adjusted odds ratio = 3.30, 95% confidence interval [1.20, 9.05], p < .05). These results show that older adults with low health literacy are more likely to have poor understanding of the Medicare program and yet more likely to believe that their understanding of the program is adequate. This combination of factors may place them at increased risk for poor access to information about the Medicare program and diminish their ability to make fully informed choices. PMID- 27676125 TI - A global experimental dataset for assessing grain legume production. AB - Grain legume crops are a significant component of the human diet and animal feed and have an important role in the environment, but the global diversity of agricultural legume species is currently underexploited. Experimental assessments of grain legume performances are required, to identify potential species with high yields. Here, we introduce a dataset including results of field experiments published in 173 articles. The selected experiments were carried out over five continents on 39 grain legume species. The dataset includes measurements of grain yield, aerial biomass, crop nitrogen content, residual soil nitrogen content and water use. When available, yields for cereals and oilseeds grown after grain legumes in the crop sequence are also included. The dataset is arranged into a relational database with nine structured tables and 198 standardized attributes. Tillage, fertilization, pest and irrigation management are systematically recorded for each of the 8,581 crop*field site*growing season*treatment combinations. The dataset is freely reusable and easy to update. We anticipate that it will provide valuable information for assessing grain legume production worldwide. PMID- 27676126 TI - Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis. AB - AIM: There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects of medication hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma biomarkers in drug-free patients with BD and SZ. METHODS: We comprehensively analyzed plasma metabolites using capillary electrophoresis time of-flight mass spectrometry in patients with SZ (n = 17), BD (n = 6), and major depressive disorder (n = 9) who had not received psychotropics for at least 2 weeks, and in matched healthy controls (n = 19). The results were compared with previous reports, or verified in an independent sample set using an alternative analytical approach. RESULTS: Lower creatine level and higher 2-hydroxybutyric acid level were observed in SZ than in controls (uncorrected P = 0.016 and 0.043, respectively), whereas they were unaltered in a previously reported dataset. Citrulline was nominally significantly decreased in BD compared to controls (uncorrected P = 0.043); however, this finding was not replicated in an independent sample set of medicated patients with BD. N-methyl-norsalsolinol, a metabolite of dopamine, was suggested as a candidate biomarker of BD; however, it was not detected by the other analytical method. Levels of betaine, a previously reported candidate biomarker of schizophrenia, were unchanged in the current dataset. CONCLUSION: Our preliminary findings suggest that the effect of confounding factors, such as duration of illness and medication, should be carefully controlled when searching for plasma biomarkers. Further studies are required to establish robust biomarkers for these disorders. PMID- 27676127 TI - Relationship Between Two Common Lipoprotein Lipase Variants and the Metabolic Syndrome and Its Individual Components. AB - BACKGROUND: Common lipoprotein lipase (LPL) variants are important determinants of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol (C) concentrations. High TG/low HDL-C tend to cluster with hypertension, glucose intolerance, and abdominal obesity and comprise the metabolic syndrome (MetS). The role of LPL variants as a cause of MetS is unclear. This study investigated the relationship between two common LPL variants and the presence of MetS and its individual components. METHODS: Cross-sectional study, including 2348 Danish women (50.7%) and men, age 41-72 years, without known cardiovascular disease. Carrier status for the two common LPL variants: 447Ter (low TG/high HDL-C) and 291Ser (high TG/low HDL-C) was determined. The prevalence of MetS according to the National Cholesterol Education Program criteria was 16.6%. RESULTS: Of the 2348 participants, 19.8% had the 447Ter variant and 4.9% had the 291Ser variant. Compared with the reference variant, the prevalence of MetS was lower in carriers of the 447Ter variant (11.2% vs. 17.9%, P < 0.001) but with no difference in carriers of the 291Ser variant (18.4% vs. 16.5%, P = 0.59). Adjusted for age, sex, smoking, physical activity, alcohol consumption, and highest sex-specific insulin quartile, the relative risk of MetS was 0.63 (95% confidence interval [CI] 0.45-0.89, P < 0.01) for carriers of the 447Ter variant and 1.20 (95% CI 0.70-2.03, P > 0.05) for carriers of the 291Ser variant. Both LPL variants were associated with high TG/low HDL-C (P < 0.01), but not with the MetS components waist circumference, hypertension, and glucose intolerance (P > 0.05). CONCLUSION: The two common LPL variants were associated with MetS through their effect on high TG/low HDL-C. PMID- 27676128 TI - Three Dimensional Quantification of Microarchitecture and Vessel Regeneration by Synchrotron Radiation Microcomputed Tomography in a Rat Model of Spinal Cord Injury. AB - A full understanding of the mechanisms behind spinal cord injury (SCI) processes requires reliable three-dimensional (3D) imaging tools for a thorough analysis of changes in angiospatial architecture. We aimed to use synchrotron radiation MUCT (SRMUCT) to characterize 3D temporal-spatial changes in microvasculature post SCI. Morphometrical measurements revealed a significant decrease in vascular volume fraction, vascular bifurcation density, vascular segment density, and vascular connectivity density 1 day post-injury, followed by a gradual increase at 3, 7, and 14 days. At 1 day post-injury, SRMUCT revealed an increase in vascular tortuosity (VT), which reached a plateau after 7 days and decreased slightly during the healing process. In addition, SRMUCT images showed that vessels were largely concentrated in the gray matter 1 day post-injury. The maximal endothelial cell proliferation rate was detected at 7 days post-injury. The 3D morphology of the cavity appears in the spinal cord at 28 days post injury. We describe a methodology for 3D analysis of vascular repair in SCI and reveal that endogenous revascularization occurs during the healing process. The spinal cord microvasculature configuration undergoes 3D remodeling and modification during the post-injury repair process. Examination of these processes might contribute to a full understanding of the compensatory vascular mechanisms after injury and aid in the development of novel and effective treatment for SCI. PMID- 27676129 TI - Spatial Localization and Quantitation of Androgens in Mouse Testis by Mass Spectrometry Imaging. AB - Androgens are essential for male development and reproductive function. They are transported to their site of action as blood-borne endocrine hormones but can also be produced within tissues to act in intracrine and paracrine fashions. Because of this, circulating concentrations may not accurately reflect the androgenic influence within specific tissue microenvironments. Mass spectrometry imaging permits regional analysis of small molecular species directly from tissue surfaces. However, due to poor ionization and localized ion suppression, steroid hormones are difficult to detect. Here, derivatization with Girard T reagent was used to charge-tag testosterone and 5alpha-dihydrotestosterone allowing direct detection of these steroids in mouse testes, in both basal and maximally stimulated states, and in rat prostate. Limits of detection were ~0.1 pg for testosterone. Exemplary detection of endogenous steroids was achieved by matrix assisted laser desorption ionization and either Fourier transform ion cyclotron resonance detection (at 150 MUm spatial resolution) or quadrupole-time-of-flight detection (at 50 MUm spatial resolution). Structural confirmation was achieved by collision induced fragmentation following liquid extraction surface analysis and electrospray ionization. This application broadens the scope for derivatization strategies on tissue surfaces to elucidate local endocrine signaling in health and disease. PMID- 27676130 TI - Conducting Block Copolymer Binders for Carbon-Free Hybrid Vanadium Pentoxide Cathodes with Enhanced Performance. AB - Polymeric binders are essential to battery electrodes, mechanically stabilizing the active materials. Most often, these binders are insulating, and conductive carbons must be added to the electrode structure. Conductive polymer binders, those that transport both ions and electrons, are of primary interest because they potentially eliminate the need for carbon additives. However, it is challenging to incorporate both ion- and electron-conductive polymeric binders into electrode systems because of differences in physical affinities among the two polymer types and the electroactive material. Here, we investigate amphiphilic polymeric binders comprised of electron- and ion-conducting poly(3 hexylthiophene)-block-poly(ethylene oxide) (P3HT-b-PEO) as compared to P3HT, PEO, and a blend of P3HT/PEO homopolymers in carbon-free V2O5 cathodes. The electrode with P3HT-b-PEO binder has the highest capacity of 190 mAh/g, whereas V2O5 is only 77 mAh/g at a C rate of 0.1 after over 200 cycles: a 2.5-fold improvement. Similarly P3HT, PEO, and the blend have capacities of 139, 130, and 70 mAh/g, which are not nearly as impressive as the block copolymer binder. The unique architecture of P3HT-b-PEO, wherein P3HT and PEO blocks are covalently bonded, promotes the uniform distribution of conductive binders within the V2O5 structure, whereas the analogous P3HT/PEO blend suffers from phase separation. This work demonstrates that conductive block copolymer binders enable carbon-free electrodes for lithium-ion battery systems. PMID- 27676133 TI - Synthesis of Quinazolines from N,N'-Disubstituted Amidines via I2/KI-Mediated Oxidative C-C Bond Formation. AB - An I2/KI-promoted oxidative C-C bond formation reaction from C(sp3)-H and C(sp2) H bonds has been used to construct quinazoline skeletons from N,N'-disubstituted amidines. The required substrates are readily prepared from the corresponding acyl chlorides, anilines, and alkyl/benzylamines by sequential amidation, chlorination, and amination reactions. Under the optimal oxidative cyclization conditions, all these amidines were conveniently transformed into the expected products in moderate to good yields. This practical and environmentally benign approach works well with crude amidine intermediates and can also be carried out on a gram scale. PMID- 27676132 TI - Interactions of the Disordered Domain II of Hepatitis C Virus NS5A with Cyclophilin A, NS5B, and Viral RNA Show Extensive Overlap. AB - Domain II of the nonstructural protein 5 (NS5A) of the hepatitis C virus (HCV) is involved in intermolecular interactions with the viral RNA genome, the RNA dependent RNA polymerase NS5B, and the host factor cyclophilin A (CypA). However, domain II of NS5A (NS5ADII) is largely disordered, which makes it difficult to characterize the protein-protein or protein-nucleic acid interfaces. Here we utilized a mass spectrometry-based protein footprinting approach in attempts to characterize regions forming contacts between NS5ADII and its binding partners. In particular, we compared surface topologies of lysine and arginine residues in the context of free and bound NS5ADII. These experiments have led to the identification of an RNA binding motif (305RSRKFPR311) in an arginine-rich region of NS5ADII. Furthermore, we show that K308 is indispensable for both RNA and NS5B binding, whereas W316, further downstream, is essential for protein-protein interactions with CypA and NS5B. Most importantly, NS5ADII binding to NS5B involves a region associated with RNA binding within NS5B. This interaction down regulated RNA synthesis by NS5B, suggesting that NS5ADII modulates the activity of NS5B and potentially regulates HCV replication. PMID- 27676131 TI - Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis. AB - Articular bone erosion in rheumatoid arthritis (RA) is mediated by the interaction between inflammation and pathways regulating bone metabolism. Inflammation promotes osteoclastogenesis and also inhibits osteoblast function, further contributing to the persistence of erosions. MicroRNAs (miRNAs) are important regulators of skeletal remodeling and play a role in RA pathogenesis. We therefore determined the expression of miRNAs in inflamed synovial tissue and the role they play in pathways regulating osteoblast and osteoclast function. Using the serum transfer mouse model of RA in C57BL/6 mice, we performed Fluidigm high-throughput qPCR-based screening of miRNAs from nonarthritic and arthritic mice. Global gene expression profiling was also performed on Affymetrix microarrays from these same synovial samples. miRNA and mRNA expression profiles were subjected to comparative bioinformatics. A total of 536 upregulated genes and 417 downregulated genes were identified that are predicted targets of miRNAs with reciprocal expression changes. Gene ontology analysis of these genes revealed significant enrichment in skeletal pathways. Of the 22 miRNAs whose expression was most significantly changed (p < 0.01) between nonarthritic and arthritic mice, we identified their targets that both inhibit and promote bone formation. These miRNAs are predicted to target Wnt and BMP signaling pathway components. We validated miRNA array findings and demonstrated that secretion of miR-221-3p in exosomes was upregulated by synovial fibroblasts treated with the proinflammatory cytokine TNF. Overexpression of miR-221-3p suppressed calvarial osteoblast differentiation and mineralization in vitro. These results suggest that miRNAs derived from inflamed synovial tissues may regulate signaling pathways at erosion sites that affect bone loss and potentially also compensatory bone formation. (c) 2016 American Society for Bone and Mineral Research. PMID- 27676134 TI - Long-term immune and virological response in HIV-infected patients receiving antiretroviral therapy. AB - WHAT IS KNOWN AND OBJECTIVE: The trajectory of HIV viral load and CD4 count and the occurrence of clinical events are primary considerations in the evaluation of antiretroviral therapy (ART) success or failure, yet a large number of studies do not describe these events from the point of therapy initiation. This study aims to describe the virological and immune response to ART and factors associated with immune and virological success in outpatients from a HIV/AIDS clinic in southern Brazil from therapy initiation. METHODS: Longitudinal observational with ambidirectional data collection study with adult patients followed for at least 12 months after enrolment. Outcomes include (i) favourable immune response, defined as CD4 count >=200 cells/mm3; and (ii) virological success, defined as viral load below the limit of detection (50 copies/mL). RESULTS: The study included 332 patients, mostly men (63%), whose mean age was 40 (+/-10) years and with median family income of BR$ 490.00 per month (IQR: 350-875). Before starting ART, 43% of patients had indications of stable immune status (CD4 count >=200 cells/mm3); the median CD4 count was 179 cells/mm3 (IQR: 93.5, 267) and increased to 379.5 cells/mm3 (IQR: 236.5, 591.3). The proportion of patients with CD4 count >=200 cells/mm3 increased from 76% to 83%, and with undetectable viral load (UVL) increased from 51.7% to 73%. Factors associated with immune success at the end of study follow-up were as follows: female gender, pretreatment CD4 count >=200 cells/mm3, previous UVL (measured when started prospective follow-up) and treatment with three drugs compared with >=4. Factors associated with virological success were as follows: UVL (measured when started prospective follow-up) and use of three drugs compared with >=4. WHAT IS NEW AND CONCLUSIONS: Results of this study show that a large proportion (73%) of patients have rapid and successful immune and virological responses to ART and that factors which predict this response include starting ART early, whereas viral load is low and CD4 count is high, with fewer drugs. These results further support the ongoing need for ongoing programmes to increase early HIV testing, early linkage to and treatment with ART, and increased viral suppression. PMID- 27676135 TI - Diffusivities of Ternary Mixtures of n-Alkanes with Dissolved Gases by Dynamic Light Scattering. AB - Theoretical approaches suggest that dynamic light scattering (DLS) signals from low-molecular-weight ternary mixtures are governed by fluctuations in temperature as well as two individual contributions from fluctuations in concentration that are related to the eigenvalues of the Fick diffusion matrix. Until now, this could not be proven experimentally in a conclusive way. In the present study, a detailed analysis of DLS signals in ternary mixtures consisting of n-dodecane (n C12H26) and n-octacosane (n-C28H58) with dissolved hydrogen (H2), carbon monoxide (CO), or water (H2O) as well as of n-C12H26 or n-C28H58 with dissolved H2 and CO is given for temperatures up to 523 K and pressures up to 4.1 MPa. Thermal diffusivities of pure n-C12H26 and n-C28H58 as well as thermal and mutual diffusivities of their binary mixtures being the basis for the ternary mixtures with dissolved gas were studied for comparison purposes. For the investigated ternary mixtures, three individual signals could be distinguished in the time resolved analysis of scattered light intensity by using photon correlation spectroscopy (PCS). For the first time, it could be evidenced that these signals are clearly associated with hydrodynamic modes. In most cases, the fastest mode observable for ternary mixtures is associated with the thermal diffusivity. The two further modes obviously related to the molecular mass transport are observable on different time scales and comparable to the modes associated with the concentration fluctuations in the respective binary mixtures. Comparison of the experimental data with results from molecular dynamics simulations revealed very good agreement. PMID- 27676136 TI - Spermatozoa from normozoospermic fertile and infertile individuals convey a distinct miRNA cargo. AB - Deciphering the underlying causes of idiopathic male infertility is one of the main challenges in reproductive medicine. This is especially relevant in infertile patients displaying normal seminal parameters and no urogenital or genetic abnormalities. In these cases, the search for additional sperm biomarkers is of high interest. This study was aimed to determine the implications of the sperm miRNA expression profiles in the reproductive capacity of normozoospermic infertile individuals. The expression level of 736 miRNAs was evaluated in spermatozoa from eight normozoospermic infertile males using TaqMan(r) qRT-PCR. Results were contrasted with data from 10 control normozoospermic fertile individuals analyzed under the same conditions. Clustering analysis of miRNA expression data separated the individuals according to their fertility condition (fertile and infertile). Fifty-seven miRNAs were differentially expressed (DE miRNAs) between populations; 20 of them was regulated by a host gene promoter that in three cases comprised genes involved in fertility. The predicted targets of the DE-miRNAs (n = 8,606) unveiled a significant enrichment of biological processes related to embryonic morphogenesis and chromatin modification. Normozoospermic infertile individuals exhibit a specific sperm miRNA expression profile clearly differentiated from normozoospermic fertile individuals. This miRNA cargo has potential implications in the individuals' reproductive competence. PMID- 27676137 TI - Resident-Centered Care in 10 U.S. Nursing Homes: Residents' Perspectives. AB - PURPOSE: With increased focus on resident-centered care (RCC) as an organizational imperative and a guiding principle of culture change for long-term care communities, evaluation of its success has centered primarily on the organizational perspective. METHODS: For this case report, we examine resident perspectives of RCC in 10 nursing homes across the United States that had adopted RCC as a philosophy and model of care for at least 12 months with a maximum engagement of 3 years using a phenomenological approach. FINDINGS: Qualitative findings from 20 focus groups with residents in 10 nursing homes suggest that RCC has meaning in ways that are consistent with intentions at the national and state levels to advance culture change in nursing homes, including efforts to create a more homelike environment, increase resident decision making and direction of his or her lifestyle, and put residents first. CLINICAL RELEVANCE: Residents attribute increased choice in wake and bed times, being heard by organizational leaders, and consistent staff assignment as positive changes since RCC began. However, according to residents, aspects of institutional life in nursing homes, inconsistent with RCC, remain. Residents identified three areas of improvement that would make nursing homes more resident centered. The three areas are response time, access to nature, and transparency about illness and death in the community. PMID- 27676138 TI - Automated system measuring triple oxygen and nitrogen isotope ratios in nitrate using the bacterial method and N2 O decomposition by microwave discharge. AB - RATIONALE: Triple oxygen and nitrogen isotope ratios in nitrate are powerful tools for assessing atmospheric nitrate formation pathways and their contribution to ecosystems. N2 O decomposition using microwave-induced plasma (MIP) has been used only for measurements of oxygen isotopes to date, but it is also possible to measure nitrogen isotopes during the same analytical run. METHODS: The main improvements to a previous system are (i) an automated distribution system of nitrate to the bacterial medium, (ii) N2 O separation by gas chromatography before N2 O decomposition using the MIP, (iii) use of a corundum tube for microwave discharge, and (iv) development of an automated system for isotopic measurements. Three nitrate standards with sample sizes of 60, 80, 100, and 120 nmol were measured to investigate the sample size dependence of the isotope measurements. RESULTS: The delta17 O, delta18 O, and Delta17 O values increased with increasing sample size, although the delta15 N value showed no significant size dependency. Different calibration slopes and intercepts were obtained with different sample amounts. The slopes and intercepts for the regression lines in different sample amounts were dependent on sample size, indicating that the extent of oxygen exchange is also dependent on sample size. The sample-size dependent slopes and intercepts were fitted using natural log (ln) regression curves, and the slopes and intercepts can be estimated to apply to any sample size corrections. When using 100 nmol samples, the standard deviations of residuals from the regression lines for this system were 0.50/00, 0.30/00, and 0.10/00, respectively, for the delta18 O, Delta17 O, and delta15 N values, results that are not inferior to those from other systems using gold tube or gold wire. CONCLUSIONS: An automated system was developed to measure triple oxygen and nitrogen isotopes in nitrate using N2 O decomposition by MIP. This system enables us to measure both triple oxygen and nitrogen isotopes in nitrate with comparable precision and sample throughput (23 min per sample on average), and minimal manual treatment. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27676139 TI - Responses of juvenile southern flounder exposed to Deepwater Horizon oil contaminated sediments. AB - The Deepwater Horizon oil spill released millions of barrels of crude oil into the northern Gulf of Mexico, much of which remains associated with sediments and can have continuing impacts on biota. Juvenile southern flounder (Paralichthys lethostigma) were exposed for 28 d in the laboratory under controlled conditions to reference and Deepwater Horizon oil-contaminated sediments collected from coastal Louisiana to assess the impacts on an ecologically and commercially important benthic fish. The measured polycyclic aromatic hydrocarbon (PAH) concentrations in the sediments ranged from 0.25 mg/kg to 3940 mg/kg suite of 50 PAH analytes (tPAH50). Mortality increased with both concentration and duration of exposure. Exposed flounder length and weight was lower compared to controls after 28 d of exposure to the sediments with the highest PAH concentration, but condition factor was significantly higher in these fish compared with all other treatments. Histopathological analyses showed increased occurrence of gill abnormalities, including telangiectasis, epithelial proliferation, and fused lamellae in flounder exposed to sediments with the highest tPAH50 concentrations. In addition, hepatic vascular congestion and macrovesicular vacuolation were observed in flounder exposed to the more contaminated sediments. These data suggest that chronic exposure to field collected oil-contaminated sediments results in a variety of sublethal impacts to a benthic fish, with implications for long-term recovery from oil spills. Environ Toxicol Chem 2017;36:1067-1076. (c) 2016 SETAC. PMID- 27676140 TI - Lone-Pair-Electron-Driven Ionic Displacements in a Ferroelectric Metal-Organic Hybrid. AB - A displacive-type mechanism, which accounts for the occurrence of ferroelectricity in most inorganic ferroelectrics, is rarely found in molecule based ferroelectrics. Its role is often covered by the predominant order-disorder one. Herein, we report a lone-pair-electron-driven displacive-type ferroelectric organic-inorganic hybrid compound, [H2dmdap][SbCl5] (1; dmdap = N,N-dimethyl-1,3 diaminopropane). The structure of 1 features a typical zigzag chain of [SbCl5]infinity containing cis-connected anionic octahedra. The compound undergoes a second-order paraelectric-ferroelectric phase transition at 143 K (P21/c <-> Pc) with a saturation polarization of 1.36 MUC.cm-2 and a coercive field of 3.5 kV.cm-1 at 119 K. Theoretical study discloses the ferroelectricity mainly originating from the relative displacements of the Sb and Cl ions in the crystal lattice, which are driven by the 5s2 lone-pair electrons of the SbIII center. Furthermore, on the basis of analysis, possible routes are suggested to enhance ferroelectric polarization in this class of compounds. PMID- 27676143 TI - Physical Exercise in Patients with Fabry Disease - a Pilot Study. AB - The aim of this study was to assess the extent of exercise intolerance in Fabry disease (FD) patients and to report individual effects of physical exercise. Exercise capacity and strength of 14 patients (mean age 46 years, 6 females) were determined using cycle ergometry and isokinetic measurements. Patients performed a strength/circuit exercise training protocol for 12 months. The mean relative maximum performance of the group was low at baseline and increased by 12.1% (baseline: 1.9 [0.9-3.4] W.kg-1vs. re-test: 2.1 [1.1-3.8] W.kg-1; p=0.035) during the study. Patients' mean baseline maximum performance blood lactate of 5.4 [1.3 9.9] mmol.L-1 increased to a mean of 7.2 (2.4-10.2) mmol.L-1 (p=0.038). Mean strength of the lower limbs (left/right extensors and flexors, total work of 5 sets) changed from 2269 (1017-2913) kg.m2.s - 2 to 2325 (1359-3107) kg.m2.s-2 (not significant). Patients reported increased well-being, daily activity and reduced fatigue during the study. Our results indicate that exercise intolerance in FD patients often results from physical inactivity. FD patients may perform exercise training to improve exercise capacity and muscle strength. Future studies will address the clinical benefits of exercise in FD. PMID- 27676144 TI - High-intensity Interval Training in the Boundaries of the Severe Domain: Effects on Sprint and Endurance Performance. PMID- 27676142 TI - Post-Exercise Neurovascular Control in Chronic Heart Failure Patients. AB - It remains unknown whether or not a reduction in muscle sympathetic nerve activity in heart failure patients is associated over time with the effects of long- or short-term repeated exercise. 10 chronic heart failure patients, age 49+/-3 years old, functional class I-III NYHA, ejection fraction <40% were randomly submitted to either an acute bout of moderate continuous exercise OR high-intensity interval exercise. Muscle sympathetic nerve activity (microneurography) and forearm blood flow (venous occlusion plethysmography) were evaluated pre- and post-exercise sessions. The moderate exercise consisted of cycle exercise at an intensity corresponding to anaerobic threshold. The interval exercise consisted of a 2-min cycle exercise at intensity corresponding to anaerobic threshold, followed by a 1-min exercise set at respiratory compensation point. Exercise capacity was evaluated by cardiopulmonary exercise test. The caloric expenditure in both sessions was 100 kcal. Baseline muscle sympathetic nerve activity and forearm blood flow levels were not different between sessions. Moderate or high-intensity exercise caused no significant changes in muscle sympathetic nerve activity and forearm blood flow. These findings suggest that the reduction in muscle sympathetic nerve activity and the increase in forearm blood flow provoked by exercise training in chronic heart failure patients are due to cumulative effects over time. PMID- 27676141 TI - Effect of Visual Impairment on Physical and Cognitive Function in Old Age: Findings of a Population-Based Prospective Cohort Study in Germany. AB - OBJECTIVES: To examine how visual impairment affects physical and cognitive function in old age. DESIGN: A longitudinal population-based prospective cohort study. SETTING: General practitioner offices at six study centers in Germany. They were observed every 1.5 years over four waves. PARTICIPANTS: Individuals aged 77-101 at follow-up Wave 2 (N = 2,394). MEASUREMENTS: Physical and cognitive function were assessed using an adapted scale that had been previously developed, and visual impairment was rated on a Likert scale (none, mild, severe or profound). RESULTS: Adjusting for sociodemographic factors and comorbidity, linear fixed-effects regression showed that the onset of severe visual impairment was associated with a decline in physical function score in the total sample (beta = -0.15, P = .01) and in women (beta = -.15, P = .03). Moreover, the onset of severe visual impairment was associated with decline in cognitive function score in the total sample (beta = -0.38, P < .001) and in women (beta = -0.38, P < .001) and men (beta = -0.37, P = .001). CONCLUSION: Visual impairment affects physical and cognitive function in old age. Interventional strategies to postpone visual impairment may contribute to maintaining physical and cognitive function. PMID- 27676145 TI - Is there a Relationship between Bone Morphology and Injured Ligament on Imaging Studies and Laxity on Ankle Stress Radiographs? AB - This study aimed to investigate the relationship between bone morphology and injured ligaments on imaging studies and laxity on ankle stress radiographs in patients with lateral ankle instability. In total, 115 patients who had undergone ankle MRI, ankle radiography, and stress radiography were included. Distal tibial articular surface angle, bimalleolar tilt, medial and lateral malleolar relative length, medial malleolar slip angle, anterior inclination of the tibia, and fibular position were measured on ankle radiographs. Tibiotalar tilt angle and anterior translation of the talus were measured on ankle stress radiographs. Degree of ligament injury was evaluated on ankle MRIs. Multiple regression analysis was performed using the following independent variables: age, sex, and factors significantly associated with ankle stress view on univariate linear regression analysis. Age (p=0.041), sex (p=0.014), degree of anterior talofibular ligament injury (p<0.001), and bimalleolar tilt (p=0.016) were correlated with tibiotalar tilt angle. Fibular position and degree of posterior talofibular ligament injury were factors significantly related to anterior translation of the talus. Differences in patient characteristics might predispose ankle stress radiograph results. Comparison of both ankles on stress radiographs is superior to applying fixed numerical values to the injured side in order to reduce the influence of patient factors. PMID- 27676147 TI - Validation of Body Volume Acquisition by Using Elliptical Zone Method. AB - The elliptical zone method (E-Zone) can be used to obtain reliable body volume data including total body volume and segmental volumes with inexpensive and portable equipment. The purpose of this research was to assess the accuracy of body volume data obtained from E-Zone by comparing them with those acquired from the 3D photonic scanning method (3DPS). 17 male participants with diverse somatotypes were recruited. Each participant was scanned twice on the same day by a 3D whole-body scanner and photographed twice for the E-Zone analysis. The body volume data acquired from 3DPS was regarded as the reference against which the accuracy of the E-Zone was assessed. The relative technical error of measurement (TEM) of total body volume estimations was around 3% for E-Zone. E-Zone can estimate the segmental volumes of upper torso, lower torso, thigh, shank, upper arm and lower arm accurately (relative TEM<10%) but the accuracy for small segments including the neck, hand and foot were poor. In summary, E-Zone provides a reliable, inexpensive, portable, and simple method to obtain reasonable estimates of total body volume and to indicate segmental volume distribution. PMID- 27676146 TI - Comparison of 3 Methods for Computing Loading Rate during Running. AB - Tibial stress fractures are among the most common and potentially serious overuse injuries in runners. The fractures are thought to be related in part, to excessive loading variables, such as vertical average loading rate (VALR) and vertical instantaneous loading rate (VILR). Although there are several methods for calculating loading rate in running, little is known about the differences between the results produced by these methods. The purpose of this study was to compare 3 previously published methods of calculating VALR and VILR during running. 9 male participants ran on a treadmill at 2.5, 3.0, and 3.5 m/s. VALR and VILR were calculated from vertical ground reaction force using 3 methods that differed by the period over which the loading rates were calculated; foot strike to first peak (method A), from 20 to 80% of the time to first peak (method B), and over the first 50 ms after foot strike (method C). There were significant differences among methods with regard to VALR, but not VILR. Therefore, the results of the present study suggest that VILR is preferable to VALR for consistent evaluation among methods, which make it more acceptable to make study comparisons. PMID- 27676148 TI - Short-term Effects of Diet and Activity Changes on Inflammation and Insulin Resistance. AB - The present study focused on rapid responses of inflammation markers and insulin resistance to dietary restriction and exercise in inactive patients. 13 obese women were included during a 5-day time frame during which decreases in food intake (-1 378+/-298 kcal) were associated with 2 exercise sessions (80 and 40 min). Circulating inflammatory biomarkers, insulin resistance index and muscle soreness were measured in fasted conditions. Fasting plasma concentrations of CRP and insulin resistance index decreased over the period (respectively, p=0.02 and p=0.01), concentrations of IL-6 and TNF-alpha appeared unchanged (p>0.05). Changes in IL-6 (enhanced) and TNF-alpha (reduced) concentrations following the prolonged exercise differed compared to days with 40 min exercise and days without exercise (p<0.05). Muscle soreness appeared higher after the 80 min than after the 40-min exercise (p=0.01), and were related with IL-6 and CRP concentration changes. A 5-day period combining exercise and diet reduced the insulin-resistance index and the CRP fasting concentrations. The 80-min exercise enhanced IL-6 and lowered TNF-alpha concentration changes while days without exercise unaffected these cytokines. These exercise effects on cytokines may have benefited to the insulin resistance index. The duration and number of the exercise sessions appeared sufficient for inactive subjects to initiate health benefits without inducing negative effects on inflammation and muscle soreness. PMID- 27676149 TI - Acute Effect of Cluster and Traditional Set Configurations on Myokines Associated with Hypertrophy. AB - This study compared the acute cytokine response, and kinetic and kinematic profile following back squat exercise in resistance-trained men. In a randomized, cross-over design, 10 resistance-trained men (27+/-4 y, 1.80+/-0.07 m, 82.8+/-6.7 kg, 16.3+/-3.5% fat) performed the back squat exercise using traditional and cluster set configurations. Kinetic and kinematic data were sampled throughout each condition. Venous blood was sampled prior, immediately post, 30 min, 60 min, 24 h, and 48 h post-exercise for plasma interleukin-6 (IL-6) and interleukin-15 (IL-15). Cluster sets allowed for greater mean power (mean difference, 110 W; 90% confidence interval, +/-63 W; benefit odds, 41 447:1), driven by higher overall mean velocities (0.053 m?s-1; 0.039 m?s-1; 3 105:1) as evidenced by the lack of clear contrasts for mean force. IL-15 increased post-exercise in both conditions, but increased at 24 h (0.13 pg.mL-1; +/-0.11 pg.mL-1; 486:1) and 48 h (0.12 pg.mL 1; +/-0.10 pg.mL-1; 667:1) in traditional sets only. IL-6 increased similarly in both conditions, post-exercise through 60 min post. Cluster set configurations allow for greater mean power, attributed to higher velocities. Despite a similar response of IL-6, traditional set configuration may provide a greater stimulus for hypertrophy as evidenced by a secondary increase in IL-15. PMID- 27676150 TI - Salivary Testosterone and Cortisol Measurement in Sports Medicine: a Narrative Review and User's Guide for Researchers and Practitioners. PMID- 27676151 TI - Inter- and Intra-Individual Analysis of Post-Exercise Hypotension Following a Single Bout of High-Intensity Interval Exercise and Continuous Exercise: A Pilot Study. AB - Recently, post-exercise blood pressure (BP) has been considered a predictive tool to identify individuals who are responsive or not to BP reductions with exercise training (i. e., "high" and "low responders"). This study aimed to analyze the inter- and intra-individual BP responsiveness following a single bout of high intensity interval exercise (HIIE) and continuous exercise (CE) in normotensive men (n=14; 24.5+/-4.2 years). Mean change in BP during the 60 min period post exercise was analyzed and minimal detectable change (MDC) was calculated to classify the subjects as "low" (no post-exercise hypotension [PEH]) and "high responders" (PEH occurrence) following each exercise protocol (inter-individual analysis). The MDC for systolic and diastolic BP was 5.8 and 7.0 mmHg. In addition, a difference equal/higher than MDC between the exercise protocols was used to define an occurrence of intra-individual variability in BP responsiveness. There were "low" and "high" PEH responders following both exercise protocols (inter-individual variability) as well as subjects who presented higher PEH following a specific exercise protocol (intra-individual variability between exercise protocols). These results were observed mainly for systolic BP. In summary, PEH is a heterogeneous physiological phenomenon and, for some subjects, seems to be exercise-protocol dependent. Further investigations are necessary to confirm our preliminary findings. PMID- 27676152 TI - Dynamic Stretching does not Change the Stiffness of the Muscle-Tendon Unit. AB - The purpose of this study was to identify changes in ankle range of motion and passive mechanical properties of the muscle-tendon unit after dynamic stretching. 12 healthy subjects participated in this study. Displacement of the muscle-tendon junction was measured using ultrasonography while the ankle was passively dorsiflexed at 1 degrees /sec to its maximal dorsiflexion angle. Passive torque was also measured using an isokinetic dynamometer. Measurements were conducted pre-intervention, immediately after the intervention and 5, 10, 15 and 30 min post-intervention. The dynamic stretching consisted of four 30-s periods of ankle dorsiflexion and plantarflexion. Ankle range of motion was significantly increased immediately (from 18.3+/-1.8 degrees to 21.4+/-1.7 degrees ) and 10 min (20.9+/-1.9 degrees ) after dynamic stretching, but this change disappeared within 15 min. However, stiffness of the muscle-tendon unit and displacement of the muscle-tendon junction at the submaximal dorsiflexion angle did not differ between the experimental conditions. These results demonstrate that dynamic stretching by contracting an antagonist muscle group increases ankle range of motion temporarily without changing the passive mechanical properties of the muscle-tendon unit. The increased range of motion of the ankle after dynamic stretching might be caused by enhanced stretch tolerance. PMID- 27676153 TI - Inhibition of Hepatobiliary Transport Activity by the Antibacterial Agent Fusidic Acid: Insights into Factors Contributing to Conjugated Hyperbilirubinemia/Cholestasis. AB - Conjugated hyperbilirubinemia accompanied by cholestasis is a frequent side effect during chronic treatment with the antimicrobial agent fusidic acid. Previous studies from our laboratory, addressing mechanisms of musculoskeletal toxicity arising from coadministration of fusidic acid with statins, demonstrated the ability of fusidic acid to potently inhibit human organic anion transporting polypeptides OATP1B1 (IC50 = 1.6 MUM) and OATP1B3 (IC50 = 2.5 MUM), which are responsible for the uptake-limited clearance of statins as well as bilirubin glucuronide conjugates. In the present work, inhibitory effects of fusidic acid were characterized against additional human hepatobiliary transporters [Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and multidrug resistance-associated proteins MRP2 and MRP3] as well as uridine glucuronosyl transferase (UGT1A1), which mediate the disposition of bile acids and bilirubin (and its conjugated metabolites). Fusidic acid demonstrated concentration-dependent inhibition of human NTCP- and BSEP-mediated taurocholic acid transport with IC50 values of 44 and 3.8 MUM, respectively. Inhibition of BSEP activity by fusidic acid was also consistent with the potent disruption of cellular biliary flux (AC50 = 11 MUM) in the hepatocyte imaging assay technology assay, with minimal impact on other toxicity end points (e.g., cytotoxicity, mitochondrial membrane potential, reactive oxygen species generation, glutathione depletion, etc.). Fusidic acid also inhibited UGT1A1-catalyzed beta-estradiol glucuronidation activity in human liver microsomes with an IC50 value of 16 MUM. Fusidic acid did not demonstrate any significant inhibition of ATP-dependent LTC4 transport (IC50's > 300 MUM) in human MRP2 or MRP3 vesicles. R values, which reflect maximal in vivo inhibition, were estimated from a static mathematical model by taking into consideration the IC50 values generated in the various in vitro assays and clinically efficacious unbound fusidic acid concentrations. The magnitudes of in vivo interaction (R values) resulting from the inhibition of OATP1B1, UGT1A1, NTCP, and BSEP transport were ~1.9-2.6, 1.1-1.2, 1.0-1.1, and 1.4-1.7, respectively, which are indicative of some degree of inherent toxicity risk, particularly via inhibition of OATP and BSEP. Collectively, these observations indicate that inhibition of human BSEP by fusidic acid could affect bile acid homeostasis, resulting in cholestatic hepatotoxicity in the clinic. Lack of direct inhibitory effects on MRP2 transport by fusidic acid suggests that conjugated hyperbilirubinemia does not arise via interference in MRP2-mediated biliary disposition of bilirubin glucuronides. Instead, it is possible that elevation in the level of bilirubin conjugates in blood is mediated through inhibition of hepatic OATPs, which are responsible for their reuptake and/or downregulation of MRP2 transporter as a consequence of cholestatic injury. PMID- 27676154 TI - Phorbol-12-myristate-13-acetate (PMA) mediated transcriptional regulation of Oncostatin-M. AB - Oncostatin-M (OSM), an IL-6 family cytokine, exhibits varied roles in different patho-physiological conditions. Differential expression of OSM in response to varying stimuli indicates importance of its regulation of expression. The present study illustrated transcriptional induction of osm on treatment with chemical inducer, phorbol-12-myristate-13-acetate (PMA). Following initial hours of PMA treatment, a nuclear protein C/EBP-beta binds specifically to the CCAAT consensus sequence at the proximal end of the OSM promoter. Genistein (a specific Tyr phosphorylation inhibitor) leads to the interaction of CHOP (C/EBP Homologous Protein) with C/EBP-beta, thus negatively regulating it. Knockdown of C/EBP-beta also leads to inhibition of PMA-mediated OSM induction. PMID- 27676155 TI - Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with post traumatic sepsis. AB - INTRODUCTION: Multiple organ dysfunction syndrome (MODS) developed due to the insult of trauma is a leading cause of death. The high mortality rate in these patients with and without sepsis has been reported up to 50%, throughout the world and thus required an urgent insight to overcome this problem. OBJECTIVE: The aim of this study is to examine the differential changes in subsets of T cells, imbalance in cytokine profile, immune-paralysis (T cell anergy) in Trauma hemorrhagic shock (THS) and post traumatic sepsis patients. METHODOLOGY: 114, THS patients and 50 healthy controls were recruited in the present study. We have measured the T cell proliferation assay using dominant antigens of both gram positive (LTA, 100ng/ml) and gram negative (LPS-100ng/ml) bacteria and PHA (4MUg/ml) using radioactive thymidine (1H3) assay. Simultaneously, we have measured the culture supernatant level of cytokines using Cytokine bead assay (CBA). The other parts of this study include the analysis of different subsets of T cells. RESULTS AND CONCLUSION: We observed significantly (P<0.05) reduced T cell proliferation in THS patients as compared to control. Our study also showed patients died due to sepsis/septic shock, had significantly (p<0.05) lower T cell response and had significantly elevated levels of IL-4, IL-10andTGF-beta, but low level of IL-2andIFN-gamma in culture supernatant. THS patients who developed sepsis complication had significantly higher T regulatory cells and lower Th17 cells in comparison to non-sepsis. In conclusion, our study showed an imbalance in cell mediated immune response and disturbance in Th1/Th2/Th17 and T reg population of T helper cells and also the shifts towards Th2 and T17 in THS patients who had developed sepsis and showed poor outcomes. PMID- 27676156 TI - A randomized controlled trial examining the effects of 16 weeks of moderate-to intensive cycling and honey supplementation on lymphocyte oxidative DNA damage and cytokine changes in male road cyclists. AB - The aim of this study was to investigate whether honey supplementation (70g, ninety minutes before each training session) attenuates changes in lymphocyte counts, DNA damage, cytokines, antioxidative and peroxidative biomarkers following moderate-to-intensive exercise training in male road cyclists. Healthy nonprofessional cyclists (n=24, aged 17-26years) were randomly assigned to exercise+supplement (EX+S, n=12) and exercise (EX, n=12) groups for an experimental period of 16weeks. Moderate-to-intensive exercise training increased lymphocytes DNA damage, cytokines and peroxidative biomarkers as well as decreased antioxidative biomarkers in the EX group. These changes were significantly attenuated in the EX+S group. Furthermore, for both groups the observed changes in peroxidative and antioxidative biomarkers could be correlated positively and negatively, respectively, with lymphocyte DNA damage and cytokines. Findings suggest that honey attenuates oxidative stress and lymphocyte DNA damage after exercise, activities that are most likely attributable to its high antioxidant capacity. PMID- 27676157 TI - Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-Type and Bevirimat-Resistant HIV-1. AB - Two "privileged fragments", caffeic acid and piperazine, were integrated into bevirimat producing new derivatives with improved activity against HIV-1/NL4-3 and NL4-3/V370A carrying the most prevalent bevirimat-resistant polymorphism. The activity of one of these, 18c, was increased by 3-fold against NL4-3 and 51-fold against NL4-3/V370A. Moreover, 18c is a maturation inhibitor with improved metabolic stability. Our study suggested that integration of privileged motifs into promising natural product skeletons is an effective strategy for discovering potent derivatives. PMID- 27676158 TI - Overexpression of PP2A-C5 that encodes the catalytic subunit 5 of protein phosphatase 2A in Arabidopsis confers better root and shoot development under salt conditions. AB - Protein phosphatase 2A (PP2A) is an enzyme consisting of three subunits: a scaffolding A subunit, a regulatory B subunit and a catalytic C subunit. PP2As were shown to play diverse roles in eukaryotes. In this study, the function of the Arabidopsis PP2A-C5 gene that encodes the catalytic subunit 5 of PP2A was studied using both loss-of-function and gain-of-function analyses. Loss-of function mutant pp2a-c5-1 displayed more impaired growth during root and shoot development, whereas overexpression of PP2A-C5 conferred better root and shoot growth under different salt treatments, indicating that PP2A-C5 plays an important role in plant growth under salt conditions. Double knockout mutants of pp2a-c5-1 and salt overly sensitive (sos) mutants sos1-1, sos2-2 or sos3-1 showed additive sensitivity to NaCl, indicating that PP2A-C5 functions in a pathway different from the SOS signalling pathway. Using yeast two-hybrid analysis, four vacuolar membrane chloride channel (CLC) proteins, AtCLCa, AtCLCb, AtCLCc and AtCLCg, were found to interact with PP2A-C5. Moreover, overexpression of AtCLCc leads to increased salt tolerance and Cl- accumulation in transgenic Arabidopsis plants. These data indicate that PP2A-C5-mediated better growth under salt conditions might involve up-regulation of CLC activities on vacuolar membranes and that PP2A-C5 could be used for improving salt tolerance in crops. PMID- 27676159 TI - Autocrine IL-10 functions as a rheostat for M1 macrophage glycolytic commitment by tuning nitric oxide production. AB - Inflammatory maturation of M1 macrophages by proinflammatory stimuli such as toll like receptor ligands results in profound metabolic reprogramming resulting in commitment to aerobic glycolysis as evidenced by repression of mitochondrial oxidative phosphorylation (OXPHOS) and enhanced glucose utilization. In contrast, "alternatively activated" macrophages adopt a metabolic program dominated by fatty acid-fueled OXPHOS. Despite the known importance of these developmental stages on the qualitative aspects of an inflammatory response, relatively little is know regarding the regulation of these metabolic adjustments. Here we provide evidence that the immunosuppressive cytokine IL-10 defines a metabolic regulatory loop. Our data show for the first time that lipopolysaccharide (LPS)-induced glycolytic flux controls IL-10-production via regulation of mammalian target of rapamycin (mTOR) and that autocrine IL-10 in turn regulates macrophage nitric oxide (NO) production. Genetic and pharmacological manipulation of IL-10 and nitric oxide (NO) establish that metabolically regulated autocrine IL-10 controls glycolytic commitment by limiting NO-mediated suppression of OXPHOS. Together these data support a model where autocine IL-10 production is controlled by glycolytic flux in turn regulating glycolytic commitment by preserving OXPHOS via suppression of NO. We propose that this IL-10-driven metabolic rheostat maintains metabolic equilibrium during M1 macrophage differentiation and that perturbation of this regulatory loop, either directly by exogenous cellular sources of IL-10 or indirectly via limitations in glucose availability, skews the cellular metabolic program altering the balance between inflammatory and immunosuppressive phenotypes. PMID- 27676160 TI - Incidence of ineffective safety margin testing (<10 J) and efficacy of routine subcutaneous array insertion during implantable cardioverter defibrillator implantation. AB - The purpose of this study was to assess (1) the incidence of safety margin testing <10 J (SMT) and (2) the efficacy/safety of routinely adding a subcutaneous array (SQA) (Medtronic 6996SQ) for these patients. Patients with SMT smaller than a 10-J safety margin from maximum output were considered to have very high readings and underwent SQA insertion. These patients were compared with the rest of the patients who had acceptable SMT (>=10 J). A total of 616 patients underwent ICD implantation during the analysis period. Of those, 16 (2.6%) had SMT <10 J. By univariate analysis, younger age, and non-ischemic cardiomyopathy, were all significant predictors of SMT <10 J (p < 0.05). In all 16 cases, other methods to improve SMT prior to array insertion were attempted but failed for all patients: reversing shock polarity (n = 15), removing the superior vena cava coil (n = 14), reprogramming shock waveform (n = 9), and repositioning right ventricular lead (n = 9). Addition of the SQA successfully increased SMT to within safety margin for all patients (32 +/- 2 versus 21 +/- 3 J; p < 0.001). Follow-up (mean 48.1 +/- 21 months) was available for all patients with SQA, only 2 cases with inappropriate shocks due to atrial fibrillation had to be noted. None of the patients experienced complications due to SQA implantation. SMT <10 J occur in about 2.6% of patients undergoing ICD implantation. SQA insertion corrects this problem without procedural/mid-term complications. PMID- 27676161 TI - Flecainide challenge test: Predictors of unmasking of type 1 Brugada ECG pattern among those with non-type 1 Brugada ECG pattern. AB - BACKGROUND: Many subjects in community have non-type 1 Brugada pattern ECG with atypical symptoms, relevance of which is not clear. Provocative tests to unmask type 1 Brugada pattern in these patients would help in diagnosing Brugada Syndrome. However sensitivity and specificity of provocating drugs are variable. METHODS: We studied 29 patients referred to our institute with clinical presentation suggestive but not diagnostic of Brugada or with non-Type 1 Brugada pattern ECG. Flecainide Challenge Test (FCT) was done in these patients (IV Flecainide test in 4 patients and Oral Flecainide in 25 patients). Resting 12 lead ECG with standard precordial leads and ECG with precordial leads placed 1 Intercostal space above were performed after flecainide administration every 5 min for first 30 min and every 30 min thereafter until ECG became normal or upto 6 h. The positivity was defined as inducible Type 1 Brugada pattern in atleast 2 right sided leads. RESULT: Median age was 35(range = 5-65) years. In 16 (55%) patients the Type 1 Brugada pattern was unmasked. There were no episodes of major AV block, atrial or ventricular tachyarrhythmia. Three groups were considered for analysis: Group 1(n = 9) - FCT Positive among patients with non-type 1 Brugada ECG pattern, Group 2(n = 4) - FCT Negative among the patients with non-type 1 Brugada ECG pattern, and Group 3(n = 7) - FCT Positive among patients with no spontaneous Brugada ECG pattern. Binary logistic regression analysis found that family h/o SCD was predictive of FCT positivity in Group 1 (Odd's ratio 21, 95% Confidence interval 1.04 to 698.83, p = 0.004). CONCLUSION: Oral flecainide is useful and safe for unmasking of Type I Brugada pattern. In our study, among the many variables studied, family history of sudden cardiac death was the only predictor of flecainide test positivity among those with non-Type 1 Brugada pattern. PMID- 27676163 TI - Sudden cardiac arrest due to a single sodium channel mutation producing a mixed phenotype of Brugada and Long QT3 syndromes. AB - Inherited arrhythmia syndromes are a known, albeit rare, cause of sudden cardiac arrest which may present with characteristic electrocardiogram changes in patients with structurally normal heart. There are a variety of distinct arrhythmogenic syndromes that arise from mutations in voltage gated sodium channels, resulting in either gain or loss of function. We describe a patient with a primary inherited arrhythmia syndrome which presented as sudden cardiac arrest. Further workup revealed that her arrest was due to a combination of Brugada syndrome and Long QT3 syndrome secondary to a deleterious mutation of voltage-gated, sodium channel, type V alpha subunit (SCN5A Thr1709Met). PMID- 27676164 TI - Implantation of single lead cardioverter defibrillator with floating atrial sensing dipole in a pregnant patient without using fluoroscopy. AB - In this case report, we look into the implant procedure of a single-lead ICD with floating atrial sensing dipole in a pregnant woman, without using fluoroscopy. This system benefits the proper positioning of the lead. This is possible thanks to the simultaneous display of both the atrial and ventricular dipoles on the electro-anatomical mapping system. This technique may be taken into consideration for the few rare cases where fluoroscopy is absolutely contraindicated. PMID- 27676162 TI - Comparison between IEGM-based approach and echocardiography in AV/PV and VV delay optimization in CRT-D recipients (Quicksept study). AB - BACKGROUND: AtrioVentricular (AV) and InterVentricular (VV) delay optimization can improve ventricular function in Cardiac Resynchronization Therapy (CRT) and is usually performed by means of echocardiography. St Jude Medical has developed an automated algorhythm which calculates the optimal AV and VV delays (QuickOptTM) based on Intracardiac ElectroGrams, (IEGM), within 2 min. So far, the efficacy of the algorhythm has been tested acutely with standard lead position at right ventricular (RV) apex. Aim of this project is to evaluate the algorhythm performance in the mid- and long-term with RV lead located in mid septum. METHODS: AV and VV delays optimization data were collected in 13 centers using both echocardiographic and QuickOptTM guidance in CRTD implanted patients provided with this algorhythm. Measurements of the aortic Velocity Time Integral (aVTI) were performed with both methods in a random order at pre-discharge, 6 month and 12-month follow-up. RESULTS: Fifty-three patients were studied (46 males; age 68 +/- 10y; EF 28 +/- 7%). Maximum aVTI obtained by echocardiography at different AV delays, were compared with aVTI acquired at AV delays suggested by QuickOpt. The AV Pearson correlations were 0.96 at pre-discharge, 0.95 and 0,98 at 6- and 12- month follow-up respectively. After programming optimal AV, the same approach was used to compare echocardiographic aVTI with aVTI corresponding to the VV values provided by QuickOpt. The VV Pearson Correlation were 0,92 at pre-discharge, 0,88 and 0.90 at 6-month and 12- month follow-up respectively. CONCLUSIONS: IEGM-based optimization provides comparable results with echocardiographic method (maximum aVTI) used as reference with mid-septum RV lead location. PMID- 27676165 TI - Transhepatic permanent pacing in a child with complex cyanotic heart disease after total cavo pulmonary shunt (Kawashima repair). AB - Complex cyanotic congenital heart diseases with left isomerism are sometimes associated with atrioventricular nodal conduction disturbances that may need permanent pacing. Surgical palliation in such anatomy connecting the superior vena cava to the pulmonary artery precludes a transvenous access for an endocardial pacing lead to the ventricles. Epicardial leads in these patients fail if the pacing thresholds are very high. We report transhepatic permanent ventricular lead implantation for a young boy with heterotaxy complicated by complete heart block. PMID- 27676166 TI - Atrial flutter with atypical presentation. PMID- 27676167 TI - Leadless cardiac pacing. PMID- 27676168 TI - Morse, Lennard-Jones, and Kratzer Potentials: A Canonical Perspective with Applications. AB - Canonical approaches are applied to classic Morse, Lennard-Jones, and Kratzer potentials. Using the canonical transformation generated for the Morse potential as a reference, inverse transformations allow the accurate generation of the Born Oppenheimer potential for the H2+ ion, neutral covalently bound H2, van der Waals bound Ar2, and the hydrogen bonded one-dimensional dissociative coordinate in a water dimer. Similar transformations are also generated using the Lennard-Jones and Kratzer potentials as references. Following application of inverse transformations, vibrational eigenvalues generated from the Born-Oppenheimer potentials give significantly improved quantitative comparison with values determined from the original accurately known potentials. In addition, an algorithmic strategy based upon a canonical transformation to the dimensionless form applied to the force distribution associated with a potential is presented. The resulting canonical force distribution is employed to construct an algorithm for deriving accurate estimates for the dissociation energy, the maximum attractive force, and the internuclear separations corresponding to the maximum attractive force and the potential well. PMID- 27676169 TI - Smallest Bimetallic CoPt3 Superparamagnetic Nanoparticles. AB - We present for the first time a nonaqueous sol-gel route to produce ultrasmall (<2 nm) magnetic bimetallic CoPt3 nanoparticles (NPs). The one-pot procedure is carried out at low temperature (180 degrees C) using benzyl alcohol, acting as both reducing agent and solvent. The highly monodisperse CoPt3 NPs were investigated with innovative advanced X-ray methods (whole powder pattern modeling), HR-STEM, XPS, and SQUID magnetometry. XPS showed Co was mostly in metallic form, but with a very small amount of CoO on the NP surface. The spherical NPs had an ultrasmall diameter of 1.6 nm and could self-assemble in aligned linear chains, or nanobelts, of single NPs. They are superparamagnetic, with blocking temperature of ~20 K and coercivity at 10 K of 27.9 kA m-1 (~350 Oe). However, there is evidence of a second magnetic phase (probably CoO) in the ZFC magnetization curve, which enhances their magnetization values, without significantly affecting their superparamagnetism. PMID- 27676170 TI - Perspectives of physicians and nurses on identifying and treating psychological distress of the critically ill. AB - PURPOSE: Survivors of critical illness are frequently unable to return to their premorbid level of psychocognitive functioning following discharge. Therefore, we aimed to evaluate the burden of psychological trauma experienced by patients in the intensive care unit (ICU) as perceived by clinicians to assess factors that can impede its recognition and treatment in the ICU. MATERIALS AND METHODS: Two distinct role-specific Web-based surveys were administered to critical care physicians and nurses in medical and surgical ICUs of 2 academic medical centers. Responses were analyzed in the domains of psychological trauma, exacerbating/mitigating factors, and provider-patient communication. RESULTS: A survey was completed by 43 physicians and 55 nurses with a response rate of 62% and 37%, respectively. Among physicians, 65% consistently consider the psychological state of the patient in decision making; 77% think it is important to introduce a system to document psychological state of ICU patients; 56% would like to have more time to communicate with patients; 77% consistently spend extra time at bedside besides rounds and often hold patient's hand/reassure them. Notably, for the question about the average level of psychological stress experienced by a patient in the ICU (with 0=no stress and 100=worst stress imaginable) during initial treatment stage and by the end of the ICU stay, median assessment by both physicians and nurses was 80 for the initial stress level and 68 for the stress level by the end of the ICU stay. Among nurses, 69% always try to minimize noise and 73% actively promote patient's rest. Physicians and nurses provided multiple specific suggestions for improving ICU environment and communication. CONCLUSIONS: Both physicians and nurses acknowledge that they perceive that critically ill patients experience a high level of psychological stress that persists throughout their period of illness. Improved understanding of this phenomenon is needed to design effective therapeutic interventions. Although the lack of time is identified as significant barrier to ameliorating patient's psychological stress, the majority of clinicians indicate that they attempt to provide interventions to achieve this goal. PMID- 27676171 TI - Risk prediction models for mortality in patients with ventilator-associated pneumonia: A systematic review and meta-analysis. AB - PURPOSE: Ventilator-associated pneumonia (VAP) is a common and serious complication in patients requiring mechanical ventilation in the intensive care unit. The aims of this study were to identify models used to predict mortality in VAP patients and to assess their prognostic accuracy. METHODS: The PubMed and EMBASE were searched in February 2016. We included studies in English that evaluated models' ability to predict the risk of mortality in patients with VAP. The reported mortality with the longest follow-up was used in the meta-analysis. Prognostic accuracy was measured with the area under the receiver operator characteristic curve (AUC). RESULTS: We identified 19 articles studying 7 different models' ability to predict mortality in VAP patients. The models were Acute Physiology and Chronic Health Evaluation (APACHE) II (9 studies, n = 1398); Clinical Pulmonary Infection Score (4 studies, n = 303); "Immunodeficiency, Blood pressure, Multilobular infiltrates on chest radiograph, Platelets and hospitalization 10 days before onset of VAP" (3 studies, n = 406); "VAP Predisposition, Insult Response and Organ dysfunction" (2 studies, n = 589); Sequential Organ Failure Assessment (7 studies, n = 1019); Simplified Acute Physiology Score II (6 studies, n = 1043); and APACHE III (1 study, n = 198). APACHE II had the highest pooled AUC (95% confidence intervals), 0.72 (0.64 0.80), and CPIS had the lowest pooled AUC, 0.64 (0.55-0.72). CONCLUSION: We identified 7 models that have been evaluated for their ability to predict mortality in patients with VAP. The models had nearly equal predictive accuracies, although some models are more complex and time consuming. PMID- 27676172 TI - Novel Sperm and Gonadotropin-releasing Hormone-based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co-immunization of Male and Female Mice. AB - Improvements in long-term female contraception can be achieved by vaccinating with sperm-derived proteins. Here, recombinant proteins comprising either (i) N- (amino acid residues 1-80) or C- (amino acid residues 76-126) terminal fragments of mouse sperm protein 17 (Sp17) fused to the promiscuous T non-B cell epitope of tetanus toxoid (TT), amino acid residues 830-844 followed by di-lysine linker (KK) (TT-KK-Sp17N or TT-KK-Sp17C , respectively) or (ii) mouse equatorin (amino acid residues 21-185) fused to the T non-B cell epitope of bovine RNase (amino acid residues 94-104) were expressed in Escherichia coli. Immunization of female FVB/J mice, using alum as an adjuvant, led to the generation of high antibody titers against the above proteins. Antibodies against both N- and C-terminal fragments of Sp17 reacted with the entire capacitated mouse spermatozoa, whereas those against equatorin reacted exclusively with the equatorial region. Despite the reactivity of all immune sera, only sera from mice immunized with TT-KK-Sp17N and TT-KK-Sp17C significantly reduced mouse in vitro fertilization. Mating studies of the immunized females with un-immunized male mice revealed the highest infertility in the TT-KK-Sp17C -immunized group. In an attempt to further boost the immune response, the C-terminal fragment of Sp17 was expressed as fusion protein with a tandem repeat of gonadotropin-releasing hormone (GnRH) (Sp17C GnRH2 ). Immunization of both male and female mice with Sp17C -GnRH2 led to higher contraceptive efficacy compared to mice immunized with TT-KK-Sp17C . Interestingly, mating studies wherein partners were both immunized with Sp17C GnRH2 showed a complete failure of female mice to conceive. Thus, immunization of both males and females with Sp17C -GnRH2 has the potential to increase contraceptive efficacy. Mol. Reprod. Dev. 83: 1048-1059, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27676173 TI - A Small Cysteine-Rich Protein from the Asian Soybean Rust Fungus, Phakopsora pachyrhizi, Suppresses Plant Immunity. AB - The Asian soybean rust fungus, Phakopsora pachyrhizi, is an obligate biotrophic pathogen causing severe soybean disease epidemics. Molecular mechanisms by which P. pachyrhizi and other rust fungi interact with their host plants are poorly understood. The genomes of all rust fungi encode many small, secreted cysteine rich proteins (SSCRP). While these proteins are thought to function within the host, their roles are completely unknown. Here, we present the characterization of P. pachyrhizi effector candidate 23 (PpEC23), a SSCRP that we show to suppress plant immunity. Furthermore, we show that PpEC23 interacts with soybean transcription factor GmSPL12l and that soybean plants in which GmSPL12l is silenced have constitutively active immunity, thereby identifying GmSPL12l as a negative regulator of soybean defenses. Collectively, our data present evidence for a virulence function of a rust SSCRP and suggest that PpEC23 is able to suppress soybean immune responses and physically interact with soybean transcription factor GmSPL12l, a negative immune regulator. PMID- 27676174 TI - Post-gemcitabine therapy for patients with advanced pancreatic cancer - A comparative review of randomized trials evaluating oxaliplatin- and/or irinotecan containing regimens. AB - A systematic review and critical evaluation of randomized trial evidence for oxaliplatin- or irinotecan-containing regimens in patients with advanced pancreatic cancer previously treated with gemcitabine has not yet been published. We conducted a comparative systematic review of randomized trials evaluating oxaliplatin- or irinotecan-based therapies in patients with advanced pancreatic cancer previously treated with gemcitabine to assess trial similarity and the feasibility of performing an indirect treatment comparison (ITC). Studies were identified through PubMed and key oncology conference abstracts. The following trials met our criteria: NAPOLI-1 (nanoliposomal irinotecan [nal-IRI] or nal IRI+5-fluorouracil [5-FU]/leucovorin [LV] vs 5-FU/LV), CONKO-003 (oxaliplatin+5 FU/LV [OFF] vs 5-FU/LV), PANCREOX (oxaliplatin+5-FU/LV [mFOLFOX6] vs 5-FU/LV), and Yoo et al. (2009) (irinotecan+5-FU/LV [mFOLFIRI3] vs mFOLFOX). Fundamental differences were identified in study design (i.e., number of study sites, number of countries), patient (i.e., locally advanced vs metastatic disease, stratification variables, prior and subsequent treatments) and treatment (i.e., regimens, dose intensity) characteristics, and primary and secondary outcomes (i.e., primary vs secondary outcomes, overall survival [OS], progression-free survival [PFS]) among the 4 included trials. Our comparative review demonstrated significant dissimilarity across trials, which precluded conducting an ITC. In the absence of head-to-head nal-IRI- and/or oxaliplatin-based therapy trials, clinicians are advised to interpret these studies separately within the context of their individual patient population. PMID- 27676175 TI - Chlamydia trachomatis among Youth - Testing Behaviour and Incidence of Repeat Testing in Stockholm County, Sweden 2010-2012. AB - BACKGROUND: Widespread testing and screening for genital Chlamydia trachomatis is often advocated as an important method to halt the epidemic. Sweden has long tradition of opportunistic screening services. Nevertheless infections rates have continued to rise over the past two decades, despite increased access to testing and treatment services. METHODS: In this retrospective cohort study we describe the testing behavior for genital Chlamydia trachomatis among youth in Stockholm County, with a focus on repeated testing. Specifically we (a) study positivity rates among single and repeat testers, we (b) estimate the incidence of repeat testing and the rates of infection in repeat testing episodes, and we (c) estimate time to repeat testing and factors associated with repeat testing. All youth (aged >=12 and <26) that tested for Chlamydia trachomatis in one of 33 Youth Health Clinics in Stockholm County between 1 January 2010 and 31 December 2012 were included in the study. RESULTS: The cohort comprised a total of 65,951 individuals who did 119,699 tests during the study period. 42% of youth were repeat testers, the incidence of repeat testing was 35.0/100 person years. The overall baseline prevalence was 7.9%. Positivity rates of baseline tests among repeat testers were nearly twice as high among single testers of either sex. These were 17.1% and 9.8% among male repeat and single testers respectively. The corresponding rates for women were 9.4% and 4.3%. Positivity rates among repeat tests did not decline compared to the overall baseline positivity. Baseline test result and sex significantly influenced the occurrence of repeat testing. CONCLUSION: Among repeat testers we found high rates of Chlamydia trachomatis both at baseline and at repeat tests which suggests the possibility that this group might be continuing to engage in unsafe sexual practices. Given the extent of repeat testing and the high positivity rates on repeat testing, further research among this group is required to inquire into reasons for repeated testing. PMID- 27676176 TI - A Public Health Framework for Legalized Retail Marijuana Based on the US Experience: Avoiding a New Tobacco Industry. AB - Rachel Barry and Stanton Glantz argue that a public health framework that prioritizes public health over business interests should be used by US states and countries that legalize retail marijuana. PMID- 27676177 TI - The Chimeric Nihilism of Geriatrics. PMID- 27676178 TI - Electrochemical Growth of Single-Crystal Metal Nanowires via a Two-Dimensional Nucleation and Growth Mechanism. AB - Metallic nanowires (Au, Ag, Cu, Ni, Co, and Rh) with an average diameter of 40 nm and a length of 3-5 MUm have been fabricated by electrodeposition in the pores of track-etched polycarbonate membranes. Structural characterizations by transmission electron microscopy (TEM) and electron diffraction showed that nanowires of Au, Ag, and Cu are single-crystalline with a preferred [111] orientation, whereas Ni, Co, and Rh wires are polycrystalline. Possible mechanisms responsible for nucleation and growth for single-crystal noble metals versus polycrystalline group VIII-B metals are discussed. PMID- 27676179 TI - A Feeder-Bus Dispatch Planning Model for Emergency Evacuation in Urban Rail Transit Corridors. AB - The mobility of modern metropolises strongly relies on urban rail transit (URT) systems, and such a heavy dependence causes that even minor service interruptions would make the URT systems unsustainable. This study aims at optimally dispatching the ground feeder-bus to coordinate with the urban rails' operation for eliminating the effect of unexpected service interruptions in URT corridors. A feeder-bus dispatch planning model was proposed for the collaborative optimization of URT and feeder-bus cooperation under emergency situations and minimizing the total evacuation cost of the feeder-buses. To solve the model, a concept of dummy feeder-bus system is proposed to transform the non-linear model into traditional linear programming (ILP) model, i.e., traditional transportation problem. The case study of Line #2 of Nanjing URT in China was adopted to illustrate the model application and sensitivity analyses of the key variables. The modeling results show that as the evacuation time window increases, the total evacuation cost as well as the number of dispatched feeder-buses decrease, and the dispatched feeder-buses need operate for more times along the feeder-bus line. The number of dispatched feeder-buses does not show an obvious change with the increase of parking spot capacity and time window, indicating that simply increasing the parking spot capacity would cause huge waste for the emergent bus utilization. When the unbalanced evacuation demand exists between stations, the more feeder-buses are needed. The method of this study will contribute to improving transportation emergency management and resource allocation for URT systems. PMID- 27676180 TI - Rapid characterization of the chemical constituents of Cortex Fraxini by homogenate extraction followed by UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry and GC-MS. AB - Cortex Fraxini is an important traditional Chinese medicine. In this work, a rapid and reliable homogenate extraction method was applied for the fast extraction for Cortex Fraxini, and the method was optimized by response surface methodology. Ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry and gas chromatography with mass spectrometry were established for the separation and characterization of the constituents of Cortex Fraxini. Liquid chromatography separation was conducted on a C18 column (150 mm * 2.1 mm, 1.8 MUm), and gas chromatography separation was performed on a capillary with a 5% phenyl-methylpolysiloxane stationary phase (30 m * 0.25 mm * 0.25 mm) by injection of silylated samples. According to the results, 33 chemical compounds were characterized by liquid chromatography with mass spectrometry, and 11 chemical compounds were characterized by gas chromatography with mass spectrometry, and coumarins were the major components characterized by both gas chromatography with mass spectrometry and liquid chromatography with mass spectrometry. The proposed homogenate extraction was an efficient and rapid method, and coumarins, phenylethanoid glycosides, iridoid glycosides, phenylpropanoids, and lignans were the main constituents of Cortex Fraxini. This work laid the foundation for further study of Cortex Fraxini and will be helpful for the rapid extraction and characterization of ingredients in other traditional Chinese medicines. PMID- 27676182 TI - Parents scaffold flexible imitation during early childhood. AB - Children use imitation flexibly to acquire the instrumental skills and conventions of their social groups. This study (N=69 parent and 3- to 6-year-old child dyads) examined the impact of instrumental versus conventional language on (a) children's imitative flexibility in the context of parent-child interaction and (b) how parents scaffold children's imitation. Children in dyads presented with conventional language imitated with higher fidelity than children in dyads presented with instrumental language. Parents in dyads presented with conventional language also provided their children with more instruction to imitate and engaged in more encouragement, demonstration, and monitoring than parents in dyads presented with instrumental language. The relation between language cue and children's imitative fidelity was mediated by parent scaffolding behavior. The results provide evidence that caregivers support the development of flexible imitation during early childhood by adjusting their scaffolding according to the goal of the behavior. PMID- 27676181 TI - Multiple Minor QTLs Are Responsible for Fusarium Head Blight Resistance in Chinese Wheat Landrace Haiyanzhong. AB - Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe, is a devastating disease in wheat (Triticum aestivum L.). Use of host resistance is one of the most effective strategies to minimize the disease damage. Haiyanzhong (HYZ) is a Chinese wheat landrace that shows a high level of resistance to FHB spread within a spike (type II resistance). To map the quantitative trait loci (QTLs) in HYZ and identify markers tightly linked to the QTLs for FHB resistance, a population of 172 recombinant inbred lines (RILs) from a cross between HYZ and Wheaton (FHB susceptible) was genotyped using simple sequence repeats (SSRs) and single-nucleotide polymorphisms (SNPs) derived from genotyping-by-sequencing (GBS), and evaluated for percentage of symptomatic spikelets (PSSs) per spike in three greenhouse experiments. Six QTLs for type II resistance were identified in HYZ, indicating that multiple minor QTLs together can provide a high level of FHB resistance in wheat. The QTL with the largest effect on FHB resistance was mapped on the chromosome arm 5AS, and the other five from HYZ were mapped on the chromosomes 6B, 7D, 3B, 4B and 4D. In addition, two QTLs from Wheaton were mapped on 2B. Critical SNPs linked to the QTLs on chromosomes 5A, 6B, and 2B were converted into KBioscience competitive allele-specific PCR (KASP) assays, which can be used for marker-assisted selection (MAS) to pyramid these QTLs in wheat. PMID- 27676184 TI - Application of Fragment-Based de Novo Design to the Discovery of Selective Picomolar Inhibitors of Glycogen Synthase Kinase-3 Beta. AB - A systematic fragment-based de novo design procedure was developed and applied to discover new potent and selective inhibitors of glycogen synthase kinase-3 beta (GSK3beta). Candidate inhibitors were generated to simultaneously maximize the biochemical potency and the specificity for GSK3beta through three design steps: identification of the optimal molecular fragments for the three sub-binding regions, design of proper linking moieties to connect the fragmental building blocks, and final scoring of the generated molecules. By virtue of modifying the ligand hydration free energy term in the scoring function using hybrid scaled particle theory and the extended solvent-contact model, we identified several GSK3beta inhibitors with biochemical potencies ranging from low nanomolar to picomolar levels. Among them, the two most potent inhibitors (12 and 27) are anticipated to serve as promising starting points of drug discovery for various diseases caused by GSK3beta because of the high specificity for the inhibition of GSK3beta. PMID- 27676183 TI - Foundations of mathematics and literacy: The role of executive functioning components. AB - The current study investigated the relations between the three cognitive processes that comprise executive functioning (EF)-response inhibition, working memory, and cognitive flexibility-and individual components of mathematics and literacy skills in preschool children. Participants were 125 preschool children ranging in age from 3.12 to 5.26years (M=4.17years, SD=0.58). Approximately 53.2% were female, and the sample was predominantly Caucasian (69.8%). Results suggest that the components of EF may be differentially related to the specific components of early mathematics and literacy. For mathematics, response inhibition was broadly related to most components. Working memory was related to more advanced mathematics skills that involve comparison or combination of numbers and quantities. Cognitive flexibility was related to more conceptual or abstract mathematics skills. For early literacy, response inhibition and cognitive flexibility were related to print knowledge, and working memory was related only to phonological awareness. None of the EF components was related to vocabulary. These findings provide initial evidence for better understanding the ways in which EF components and academic skills are related and measured. Furthermore, the findings provide a foundation for further study of the components of each domain using a broader and more diverse array of measures. PMID- 27676185 TI - Diffuse Tracheal Papillomatosis. PMID- 27676186 TI - Correlating Prenatal Imaging Findings of Fetal Ventriculomegaly with the Need for Surgical Intervention in the First 3 Months after Birth. AB - BACKGROUND/AIMS: This study evaluates the predictive value of prenatal imaging measurements regarding the need for cerebrospinal fluid (CSF) diversion for fetal hydrocephalus in the first 3 months after birth. METHODS: We retrospectively reviewed a consecutive case series of patients with fetal hydrocephalus from January 2011 to December 2014 (n = 45). Prenatal measurements included head circumference (HC), biparietal diameter (BPD), and lateral ventricle (LV) width. Patients requiring CSF diversion within 12 weeks of birth were compared to those who did not require CSF diversion using the Wilcoxon rank sum test, and receiver operating characteristic analysis was used to evaluate threshold values. RESULTS: CSF diversion was required within 12 weeks of birth in 30 of 45 patients. Mean LV width (mm) during the entire pregnancy was greater for the surgery group than the nonsurgery group. Neither BPD nor HC showed differences between the groups. A mean LV size >=15 mm predicted the need for CSF diversion with a sensitivity of 67% and specificity of 73%. CONCLUSION: LV width is the prenatal imaging measurement that best predicts the need for postnatal CSF diversion. PMID- 27676187 TI - Spherical, Dimpled, and Crumpled Hybrid Colloids with Tunable Surface Morphology. AB - Surface morphology is a tool to tune physical properties of colloidal suspensions such as the wettability, viscoelasticity, and depletion attractions. Existing synthesis methods to obtain colloids with a rough surface morphology often result in colloids with nontunable surface properties. Here, we developed a synthetic approach to obtain both spherical and shape-anisotropic hybrid colloids with tunable surface morphology. With our approach, monodisperse linear polystyrene colloids, obtained in large quantities using a dispersion polymerization method, are swollen and cross-linked with styrene and 3-(trimethoxysilyl)propyl methacrylate (TPM) in the presence of the polymerization inhibitor hydroquinone. We show that, by varying only two experimental parameters, the concentration of the inhibitor and of TPM during swelling linear polystyrene colloids, three different types of particles can be synthesized. At low TPM concentrations, spherical colloids are obtained where the surface roughness can be tuned by varying the hydroquinone concentration. At intermediate TPM concentrations, single-dimpled colloids are formed with tunable dimple size. High TPM concentrations yield crumpled colloids of various shapes. Additionally, we demonstrate that all particles can be used as templates for silica coating, resulting in electrostatically stabilized silica-coated hybrid colloids or silica shells with rough, smooth, dimpled, or crumbled surface morphology. PMID- 27676188 TI - Endoscopic Diagnosis of the Invasion Depth of T1 Colorectal Carcinoma for Endoscopic Resection by Using Narrow-Band Imaging Magnification as Total Excisional Biopsy. AB - BACKGROUND/AIMS: We established a new colorectal T1 invasion depth sub classification and evaluated it to determine whether total excisional biopsy can be performed on colorectal carcinoma (CRC) cases using narrow-band imaging (NBI) magnification. METHODS: The cases included 73 T1 carcinomas selected from 173 early CRC cases. The T1 invasion depth sub-classification was defined as follows: T1a, invasion less than 1,000 MUm from the inferior border of the muscularis mucosae; T1b-1, between T1a and T1b-2; and T1b-2, T1b lesions with invasion from the deepest part of the carcinoma to within 1,000 MUm of the superior border of the muscularis propria. The T1b-2 lesions were not suitable for total excisional biopsy to be performed on them. We examined the maximum diameter of Type C2 (NBI Hiroshima classification) areas and invasion depth. RESULTS: Among 47 lesions classified as Type C2, 38 lesions showed a maximum diameter of 10 mm or less and were classified as Tis, T1a, or T1b-1. The remaining 9 lesions exceeded 10 mm, and among these, 3 cases were classified as T1b-2 (p = 0.0035). CONCLUSION: For using the new T1 invasion depth sub-classification to classify T1 CRCs in which total excisional biopsy is possible, it is useful to measure the maximum diameter of the Type C2 area. PMID- 27676189 TI - Al-Pd Nanodisk Heterodimers as Antenna-Reactor Photocatalysts. AB - Photocatalysis uses light energy to drive chemical reactions. Conventional industrial catalysts are made of transition metal nanoparticles that interact only weakly with light, while metals such as Au, Ag, and Al that support surface plasmons interact strongly with light but are poor catalysts. By combining plasmonic and catalytic metal nanoparticles, the plasmonic "antenna" can couple light into the catalytic "reactor". This interaction induces an optical polarization in the reactor nanoparticle, forcing a plasmonic response. When this "forced plasmon" decays it can generate hot carriers, converting the catalyst into a photocatalyst. Here we show that precisely oriented, strongly coupled Al Pd nanodisk heterodimers fabricated using nanoscale lithography can function as directional antenna-reactor photocatalyst complexes. The light-induced hydrogen dissociation rate on these structures is strongly dependent upon the polarization angle of the incident light with respect to the orientation of the antenna reactor pair. Their high degree of structural precision allows us to microscopically quantify the photocatalytic activity per heterostructure, providing precise photocatalytic quantum efficiencies. This is the first example of precisely designed heterometallic nanostructure complexes for plasmon-enabled photocatalysis and paves the way for high-efficiency plasmonic photocatalysts by modular design. PMID- 27676190 TI - Risk Factors and Prognosis of Cardiorenal Syndrome Type 1 in Elderly Chinese Patients: A Retrospective Observational Cohort Study. AB - BACKGROUND/AIMS: Cardiorenal syndrome type 1 (CRS1) is a syndrome characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). The aims of this study were to investigate the risk factors and the prognosis of CRS1 in elderly patients. METHODS: A total of 312 elderly patients (>=60 years old) with acute heart failure (AHF) were studied. They were assigned as CRS1 (suffered from in-hospital AKI) or NCRS1 (without AKI) group. Clinical and laboratory data were recorded. Univariate and multivariate analysis were performed to clarify the risk factors for occurrence and mortality of CRS1 in this cohort. RESULTS: Incidence of CRS1 was 52.56%. Basic estimated glomerular filtration (eGFR <60 ml/(min.1.73m2) and use of diuretics were associated with the higher risk of CRS1 in elderly patients (OR=2.239, P=0.025; OR=2.555, P=0.001; respectively). Whereas higher concentration of serum albumin was protective factor for them (OR=0.907, P=0.007). The in-hospital mortality of CRS1 was 23.2%. Dialysis, use of beta blockers or diuretics were associated with all cause death of CRS1 patients (OR=10.407, P<0.001; OR=0.312, P=0.011; OR=0.345, P=0.040; respectively). The in-hospital mortality of AHF patients was 13.1%. Higher Charlson comorbidity index, occurrence of CRS1 and dialysis were risk factors for in-hospital mortality of AHF patients (OR=4.723, P=0.041; OR=6.096, P=0.008; OR=18.743, P<0.001; respectively). CONCLUSIONS: Incidence of CRS1 in elderly patients is relatively high and associated with poor outcome. Reduced basic eGFR, lower serum albumin and use of diuretics are risk factors for the occurrence of CRS1 in elderly patients, while use of diuretics, beta blockers and dialysis during hospitalization are predictors of in-hospital mortality in patients with CRS1. These results above suggest that more suitable treatments for the elderly with CRS1 might be needed. PMID- 27676191 TI - Radiosensitization of oral tongue squamous cell carcinoma by nanosecond pulsed electric fields (nsPEFs). AB - Nanosecond pulsed electric fields (nsPEFs) are a non-thermal and non-toxic technology that induce a myriad of biological effects. They have been proven to be effective in tumor shrinkage, but few studies focus on its radiosensitization in oral tongue squamous cell carcinoma. The purpose of this research was to study the radiosensitization effect of nsPEFs on a human oral tongue cancer cell line Tca8113 and to investigate the potential antitumor mechanism. A Tca8113 cell line was tested respectively by MTT assay, clonogenic assay, flow cytometry assay, annexin V-FITC/PI assay, mitochondrial potential assay and total nitric oxide assay. Our results showed that nsPEFs had a time and field strength dependent inhibition effect on Tca8113 cells. The sensitization enhancement ratio (SER) of nsPEFs was 1.453+/-0.038. Furthermore, radiation induced G2/M arrest was augmented by treatment with nsPEFs. We observed many more Tca8113 cells showing early apoptosis after nsPEFs combined with radiotherapy. Additionally, the NO concentration was significantly increased after nsPEFs treatment. These findings indicate that combination of nsPEFs with radiotherapy can enhance the radiosensitivity of Tca8113 cells and nsPEFs could be a potential radiosensitizer for oral tongue squamous cell carcinoma. PMID- 27676192 TI - Neuropsychological assessment of executive functions following pediatric traumatic brain injury. AB - Assessment of executive functions in the adult is best captured at the stage where full maturation of brain development occurs. Assessment of executive functions of children, however, is considerably more complicated. First, assessment of executive functioning in children represents a snapshot of these developing functions at a particular time linked stage, which may have implications for further development. Second, neuropsychological measures available to assess executive functions in children are limited in number and scope and may not be sensitive to the gradual developmental changes. The present article provides an overview of the salient neurodevelopmental stages of executive functioning and discusses the utilization of recently developed neuropsychological measures to assess these stages. Comments on clinical implications of these findings regarding Traumatic Brain Injury will be provided. PMID- 27676193 TI - Inhaler Technique in Asthma: How Does It Relate to Patients' Preferences and Attitudes Toward Their Inhalers? AB - BACKGROUND: Correct inhaler technique can increase medication efficacy, reducing both dose and side effects. Patient preference for inhaler device has not been fully explored, and we hypothesized that if patients have a preference and can choose their inhaler, they might be more likely to use it correctly. Our aim was to determine the preferences, attitudes, and perceptions of patients with asthma toward their inhalers, and to evaluate whether any of these factors were related to inhalation technique. METHODS: Twenty-five patients with asthma (mean age 43.1 years) participated. Qualitative semi-structured interviews and quantitative patient satisfaction and preference questionnaires (PASAPQ) were used to explore patients' preferences, attitudes, and perceptions about their inhalers. Objective inhalation technique assessment was performed. Data were triangulated to identify characteristics that could indicate a relationship between inhaler technique, satisfaction, preference, and decision making. RESULTS: Themes from qualitative interviews were as follows: asthma inhalers and expectations; inhaler preference; characteristics of an ideal inhaler; perceived effectiveness of inhalers; and inhalers and patient decision making. PASAPQ scores indicated that all patients were at least "somewhat satisfied" with their inhalers, regardless of technique. Only 12% of inhalers were used correctly, despite pilot PASAPQ data suggesting that most patients were confident with their technique. The inhaler technique was unlikely to be related to satisfaction, perception of inhaler devices, or choice in device selection. Patients with correct inhaler technique were more aware of their asthma and expressed motivation to achieve optimal asthma control. CONCLUSIONS: The majority of the asthmatic patients did not use their inhaler(s) correctly, despite most having confidence in their technique. Patients attributed confidence in their inhaler technique to their belief that their inhaler was effective. Most patients had not been involved in decision making about which inhalation device to use. These findings highlight the lack of understanding of the important role of correct inhaler technique in asthma management. PMID- 27676195 TI - The future of lipid guidelines. AB - PURPOSE OF REVIEW: Factors influencing guideline development may result in paradigm shifts in treatment recommendations. RECENT FINDINGS: The 2013 American College of Cardiology/American Heart Association cholesterol guideline provides an example of how new methodology and findings from randomized clinical trials can result in a paradigm shift in the approach to cardiovascular prevention. This guideline moved away from a treat to cholesterol goal approach. Based on strong evidence of a net benefit in randomized clinical trials, statins were recommended to reduce atherosclerotic cardiovascular disease risk in four groups of patients most likely to benefit. In addition, improved risk prediction equations and shared decision-making were recommended for guiding statin initiation in primary prevention patients with LDL cholesterol <=190 mg/dl. Future guidelines will address the role of nonstatins for cardiovascular prevention. Improved risk prediction in statin-treated patients with and without cardiovascular disease, estimation of the potential for net benefit, and shared decision-making should be integral components of the next guideline. SUMMARY: Guidelines will continue to evolve as new data accumulate. New treatment paradigms will be needed to optimize patient outcomes. PMID- 27676194 TI - Folic Acid Supports Pluripotency and Reprogramming by Regulating LIF/STAT3 and MAPK/ERK Signaling. AB - Pluripotent stem cells act as an excellent cell source for disease therapy because of its specific characteristics of self-renewal and differentiation. Pluripotent stem cells are heterogeneous, consisting of naive stem cells as well as primed epiblast stem cells. However, the strategies and mechanisms of maintaining naive pluripotent stem cells remain unclear. In this study, we found that folic acid (FA) sustained mouse embryonic stem cell (ESC) pluripotency and enabled long-term maintenance of the naive state of ESCs under CHIR99021 conditions. Mechanistic experiments showed that STAT3 pathway partially mediated the effect of FA after which the interaction between STAT3 and importin alpha5 was enhanced. Meanwhile, MEK/ERK signaling also acted downstream of FA in maintaining ESC pluripotency. Furthermore, FA significantly promoted mouse somatic cell reprogramming. Overall, our study identified an effective chemical condition for maintaining homogeneous ESCs and highlighted the important roles of LIF/STAT3 and MEK/ERK signaling in naive ESC pluripotency. PMID- 27676196 TI - New oral agents for treating dyslipidemia. AB - PURPOSE OF REVIEW: We provide an overview of orally administered lipid-lowering therapies under development. RECENT FINDINGS: Recent data support statins for intermediate risk primary prevention, and ezetimibe for high-risk secondary prevention. Novel agents in development include bempedoic acid and gemcabene, and work continues on one remaining cholesteryl ester transfer protein inhibitor, anacetrapib, to determine whether this class can reduce cardiovascular risk. Selective peroxisome proliferator-activated receptor modulators such as K-877 are under study to determine whether they have an advantage over older fibrates. Diacylglycerol transferase inhibitors such as pradigastat appear to have potent triglyceride-lowering effects, even for patients with familial chylomicronemia syndrome. Finally, novel omega-3 preparations are available with significant triglyceride lowering, although their role in therapy remains unclear. SUMMARY: Statins will remain the backbone of lipid-lowering therapy, although several novel oral agents are promising. The common theme across drugs in development is the demonstration of good lipid-lowering effect, although lacking cardiovascular outcomes data, which will likely be necessary before any of them, can be recommended or approved for widespread use. PMID- 27676198 TI - Pharmacogenomic approaches to lipid-regulating trials. AB - PURPOSE OF REVIEW: Randomized clinical outcome trials are costly, long, and often yield neutral or modestly positive results, and these issues have impeded cardiovascular drug development in the past decade. Despite the significant reduction of cardiovascular morbidity and mortality with statins, substantial residual risk of major cardiovascular events remains. This could be because of the difficulty of demonstrating benefits of new drugs in addition to the current standard of care in unselected populations as well as the interindividual variability in drug response. Pharmacogenomics is a promising avenue for the development of novel or failed drugs and for the repurposing of other medications. RECENT FINDINGS: Several variants were identified in genes that were associated with the effects of statins on plasma lipids. Genomic studies of mutations in genes that encode drug targets have the potential to inform on the link between drug therapy acting on those targets and clinical outcomes. Recently, ADCY9 gene variants were shown to be significantly associated with responses to dalcetrapib in terms of clinical outcomes, atherosclerosis imaging, cholesterol efflux, and inflammation, which provided support for the conduct of a new prospective clinical trial in a genetically determined population. SUMMARY: Pharmacogenomics hold great potential in future lipid trials to decrease failure rates in drug development and to identify patients who will respond with greater benefits and smaller risk. PMID- 27676197 TI - Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk. AB - PURPOSE OF REVIEW: The absolute burden of cardiovascular risk remains high despite currently available preventive and therapeutic options. In search for novel therapeutic leads, mounting evidence has linked the gut microbiota as well as their metabolites to the development of cardiometabolic diseases. RECENT FINDINGS: The intestinal microbiota influences the host via different metabolic pathways as inducer of endotoxemia, formation of trimethylamine-N-oxide, production of short chain fatty acids, and is a regulator in intestinal bile acid metabolism. Disruption of the gut microbiome may disturb the homeostasis of the microbial ecosystem to an alternative stable state associated with pathophysiological traits in microbiota and host. However, causality has not been shown yet. SUMMARY: We are just beginning to understand how the gut microbiota influence our cardiometabolic health and various innovative therapeutic options are in the developing (preclinical) phase. This review focuses on the current evidence whether and to what extent the intestinal microbiota are involved in cardiovascular disease and whether this is based on merely association or causal relations. PMID- 27676199 TI - Clinical trials with cholesteryl ester transfer protein inhibitors. AB - PURPOSE OF REVIEW: Inhibition of cholesteryl ester transfer protein (CETP) has received considerable interest by virtue of its favorable effects on atherogenic and protective lipid parameters. The impact of CETP inhibitors in large clinical outcome trials will be reviewed. RECENT FINDINGS: Population and genetic studies demonstrate that low CETP activity associates with lower rates of cardiovascular events. Inhibiting CETP activity in animal models has a favorable impact on experimental atherosclerosis. Although the first CETP inhibitor to advance to an outcome trial proved to have adverse clinical effects and the next agent, a more modest inhibitor, was clinically futile, there continues to be immense interest in the potential to develop nontoxic, potent CETP inhibitors to reduce cardiovascular risk. SUMMARY: The current status of CETP inhibitors in the context of large outcomes trials will be reviewed. PMID- 27676200 TI - Effects of Hydrogel Stiffness and Extracellular Compositions on Modulating Cartilage Regeneration by Mixed Populations of Stem Cells and Chondrocytes In Vivo. AB - Cell-based therapies offer great promise for repairing cartilage. Previous strategies often involved using a single cell population such as stem cells or chondrocytes. A mixed cell population may offer an alternative strategy for cartilage regeneration while overcoming donor scarcity. We have recently reported that adipose-derived stem cells (ADSCs) can catalyze neocartilage formation by neonatal chondrocytes (NChons) when mixed co-cultured in 3D hydrogels in vitro. However, it remains unknown how the biochemical and mechanical cues of hydrogels modulate cartilage formation by mixed cell populations in vivo. The present study seeks to answer this question by co-encapsulating ADSCs and NChons in 3D hydrogels with tunable stiffness (~1-33 kPa) and biochemical cues, and evaluating cartilage formation in vivo using a mouse subcutaneous model. Three extracellular matrix molecules were examined, including chondroitin sulfate (CS), hyaluronic acid (HA), and heparan sulfate (HS). Our results showed that the type of biochemical cue played a dominant role in modulating neocartilage deposition. CS and HA enhanced type II collagen deposition, a desirable phenotype for articular cartilage. In contrast, HS promoted fibrocartilage phenotype with the upregulation of type I collagen and failed to retain newly deposited matrix. Hydrogels with stiffnesses of ~7-33 kPa led to a comparable degree of neocartilage formation, and a minimal initial stiffness was required to retain hydrogel integrity over time. Results from this study highlight the important role of matrix cues in directing neocartilage formation, and they offer valuable insights in guiding optimal scaffold design for cartilage regeneration by using mixed cell populations. PMID- 27676203 TI - Comparison of exercise training effect with different robotic devices for upper limb rehabilitation: a retrospective study. AB - BACKGROUND: Several robotic devices have been proposed for upper limb rehabilitation, but they differ in terms of application fields and the technical solutions implemented. AIM: The aim of this study was to compare the effectiveness of three different robotic devices for shoulder-elbow rehabilitation in reducing motor impairment and improving motor performance in post-stroke patients. DESIGN: Retrospective multi-center study. SETTING: Inpatient rehabilitation hospital. POPULATION: Eighty-seven chronic and subacute post-stroke patients, aged 48-85 years. METHODS: Data were obtained through a retrospective analysis of patients who underwent a 3-week rehabilitation program including robot-assisted therapy of the upper limb and conventional physical therapy. Patients were divided into three groups according to the robot device used for exercise training: 'Braccio di Ferro" (BdF), InMotion2 (IMT), and MEchatronic system for MOtor recovery after Stroke (MEMOS). They were evaluated at the beginning and end of treatment using the Fugl-Meyer (FM) and Modified Ashworth (MAS) clinical scales and by a set of robot measured kinematic parameters. RESULTS: The three groups were homogeneous for age, level of impairment, time since the acute event, and spasticity level. A significant effect of time (P<0.001) was evident on FM and kinematic parameters across all groups. The average change in the FM score was 9.5, 7.3 and 7.1 points, respectively, for BdF, IMT and MEMOS. No significant between-group differences were observed at the MAS pre- vs. post-treatment. A significant interaction between time and groups resulted for the mean velocity (MV, P<0.005) and movement smoothness parameters (nPK, P<0.001 and SM, P<0.02). The effect size (ES) was large for the FM score and MV parameter, independently of the type of robot device used. Further, the ES ranged from moderate to large for the remaining kinematic parameters except for the movement accuracy (mean distance, MD), which exhibited a small ES in the BdF and MEMOS groups. CONCLUSIONS: The motor function gains obtained during robot-assisted therapy of stroke patients seem to be independent of the type of robot device used for the training program. All devices tested in this study were effective in improving the level of impairment and motor performance. CLINICAL REHABILITATION IMPACT: This study could help rehabilitation professionals to set-up comparative studies involving rehabilitation technologies. PMID- 27676204 TI - Time to decannulation and associated risk factors in the postacute rehabilitation of critically ill patients with intensive care unit-acquired weakness: a cohort study. AB - BACKGROUND: Treatment of critical illness on intensive-care-units (ICU) results often in persistent invasive endotracheal intubation which might delay rehabilitation and increases the risk of mortality. Recent longitudinal studies have described the recovery of critically ill people, but the detailed time course of decannulation in patients with chronic critical illness with ICU acquired muscle weakness (ICUAW) is not well known. AIM: The aim of our study was to describe the decannulation times and associated risk factors in patients who are chronic critically ill with ICU acquired weakness. DESIGN: This is a cohort study. SETTING: Postacute and rehabilitation units. POPULATION: Chronic critically ill patients with ICUAW and tracheostomy tube. METHODS: We calculated the time until decannulation and used possible predictor variables to explain this time course. RESULTS: We included 122 patients with ICUAW. Successful decannulation of the tracheostomy tube was achieved after a median of 40.5 days (interquartile range= 44) after study onset and after a median of 89 days (interquartile range= 58) after onset of primary illness. Our final multivariate Cox-Proportional Hazard model included two main risk factors for decannulation: the amount of medical tubes such as catheters at admission to the rehabilitation center (adjusted hazard ratio [HR]=1.572 (95% CI: 1.021 to 2.415) and the duration of weaning from respirator in days (adjusted HR= 1.02 per day (95% CI: 1.006 to 1.03). No adverse events occurred. CONCLUSIONS: We described the detailed time course of decannulation in the rehabilitation of chronic critically ill patients and no adverse events were observed. Taken many single factors into account the quantity of medical tubes and the duration of weaning from respirator were associated risk factors for decannulation in this population. CLINICAL REHABILITATION IMPACT: Knowing an exact time course of decannulation supports medical decisions in clinical rehabilitation and might help to give a prognosis for decannulation. The amount of medical tubes and the duration of weaning from respirator may highly influence decannulation. PMID- 27676205 TI - In pursuit of change: Conceptualizing the social work response to LGBTQ microaggressions in health settings. AB - Despite the emergence of research on microaggressions targeting lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) communities in recent years, there remains an insufficiency of theoretical literature in this area. In this article, we draw on the works of Michel Foucault to conceptualize the effects of microaggressive practices on LGBTQ people accessing health and other social services, and generate insight into strategies these groups use to resist these effects. We emphasize the need for social workers, particularly those in health care settings, to support these communities' ongoing attempts at challenging the effects of microaggression, and to this end, outline several implications of our analysis for social work practice. PMID- 27676206 TI - Monoclonal antibodies for the treatment of Ebola virus disease. AB - INTRODUCTION: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMappTM and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time. PMID- 27676207 TI - Immunohistochemical localization of androgen receptors in female mole rat (Spalax leucodon) tissues. AB - Androgens exert their effects through androgen receptors (AR) in tissues. We investigated the distribution of AR in female mole rat tissues. Tissues were excised, fixed with 10% formalin and embedded in paraffin. Sections were stained after microwave antigen retrieval for immunohistochemistry. Immunostaining of AR immunostaining was detected in the nucleus or cytoplasm of the cells in the cerebral cortex, cerebellum, anterior pituitary, lung, liver, uterus and skin. Granulosa and some thecal cells in the ovary, cardiac muscle cells and adipose cells exhibited a nuclear reaction for AR. In the kidney, labeling of AR was restricted to the cytoplasm of tubule cells. We found that AR could be detected using immunohistochemistry in the nucleus or cytoplasm or both in the presence of androgens. PMID- 27676208 TI - Myelodysplastic/myeloproliferative neoplasms: a disease in need of recognition. PMID- 27676209 TI - Is Estrogen the Antidote for Menopausal Depression? PMID- 27676210 TI - Role of Some Predominant Host Immunomodulators' Single Nucleotide Polymorphisms in Severity of Hepatitis B Virus and Hepatitis C Virus Infection. AB - Hepatitis B and C infections can be either acute or chronic. The chronic infection can culminate in liver cirrhosis and hepatocellular carcinoma. Influence of the host genetic makeup on conversion of acute to chronic infection, development of cirrhosis, and hepatocellular carcinoma is an interesting area of research. Variability in different immune system genes may account for such differences in the outcome of infection. This article discusses single nucleotide polymorphisms in different host immunomodulator genes that have been frequently reported to influence the outcome of infection and severity of disease. The genetic variability could be utilized for the prediction of disease outcome and treatment responses. PMID- 27676211 TI - Determinants of quality of life in young onset dementia - results from a European multicenter assessment. AB - BACKGROUND: Promoting adaptation, improving well-being and maintaining an optimal quality of life (QOL) is an important aspect in dementia care. The purpose of this study was to identify determinants of QOL in young onset dementia, and to assess differences in QoL domains between people with Alzheimer's disease (AD) and frontotemporal dementia (FTD). METHODS: In total 135 persons with AD and 58 persons with FTD were included from two prospective cohort studies. QOL was assessed with the proxy reported quality of life in Alzheimer's disease questionnaire (QoL-AD). Possible determinants were explored using multiple linear regression and included sociodemographic variables, diagnosis, dementia severity, disease awareness, neuropsychiatric symptoms, met and unmet needs and hours of personal and instrumental care. Differences between QOL domains in people with AD and FTD were calculated using Mann-Whitney U tests. RESULTS: Lower QOL was associated with more depressive symptoms, lower disease awareness, and a higher amount of needs, both met and unmet. People with AD scored lower on the memory and higher on the friends' subscale. No differences were found for the other items. CONCLUSION: This study demonstrates a unique set of determinants of QOL in AD and FTD. Interventions directed towards these specific factors may improve QOL. PMID- 27676213 TI - Disruption of PCNA-lamins A/C interactions by prelamin A induces DNA replication fork stalling. AB - The accumulation of prelamin A is linked to disruption of cellular homeostasis, tissue degeneration and aging. Its expression is implicated in compromised genome stability and increased levels of DNA damage, but to date there is no complete explanation for how prelamin A exerts its toxic effects. As the nuclear lamina is important for DNA replication we wanted to investigate the relationship between prelamin A expression and DNA replication fork stability. In this study we report that the expression of prelamin A in U2OS cells induced both mono-ubiquitination of proliferating cell nuclear antigen (PCNA) and subsequent induction of Pol eta, two hallmarks of DNA replication fork stalling. Immunofluorescence microscopy revealed that cells expressing prelamin A presented with high levels of colocalisation between PCNA and gammaH2AX, indicating collapse of stalled DNA replication forks into DNA double-strand breaks. Subsequent protein-protein interaction assays showed prelamin A interacted with PCNA and that its presence mitigated interactions between PCNA and the mature nuclear lamina. Thus, we propose that the cytotoxicity of prelamin A arises in part, from it actively competing against mature lamin A to bind PCNA and that this destabilises DNA replication to induce fork stalling which in turn contributes to genomic instability. PMID- 27676212 TI - Racial and ethnic disparities in meeting MTM eligibility criteria among patients with asthma. AB - BACKGROUND: Asthma is one of the most frequently targeted chronic diseases in the medication therapy management (MTM) programs of the Medicare prescription drug (Part D) benefits. Although racial and ethnic disparities in meeting eligibility criteria for MTM services have been reported, little is known about whether there would be similar disparities among adults with asthma in the United States. METHODS: Adult patients with asthma (age >= 18) from Medical Expenditure Panel Survey (2011-2012) were analyzed. Bivariate analyses were conducted to compare the proportions of patients who would meet Medicare MTM eligibility criteria between non-Hispanic Blacks (Blacks), Hispanics and non-Hispanic Whites (Whites). Survey-weighted logistic regression was performed to adjust for patient characteristics. Main and sensitivity analyses were conducted to cover the entire range of the eligibility thresholds used by Part D plans in 2011-2012. RESULTS: The sample included 4,455 patients with asthma, including 2,294 Whites, 1,218 Blacks, and 943 Hispanics. Blacks and Hispanics had lower proportions of meeting MTM eligibility criteria than did Whites (P < 0.001). According to the main analysis, Blacks and Hispanics had 36% and 32% lower, respectively, likelihood of MTM eligibility than Whites (odds ratio [OR]: 0.64, 95% confidence interval [CI]: 0.45-0.90; OR: 0.68, 95% CI: 0.47-0.98, respectively). Similar results were obtained in sensitivity analyses. CONCLUSIONS: There are racial and ethnic disparities in meeting Medicare Part D MTM eligibility criteria among adult patients with asthma. Future studies should examine the implications of such disparities on health outcomes of patients with asthma and explore alternative MTM eligibility criteria. PMID- 27676214 TI - TLR4 acts as a death receptor for ultraviolet radiation (UVR) through IRAK independent and FADD-dependent pathway in macrophages. AB - UVR-induced apoptosis in cutaneous antigen presenting cells (APC) causes systemic immune suppression and is dependent on TLR4/MyD88 signalling, but the apoptotic signalling pathways have not been defined. Macrophages pretreated with lipopolysaccharide (LPS) were unresponsive to subsequent LPS treatment, however, but were susceptible to UVR-induced apoptosis. Macrophage survival and apoptotic events after UVR were also unaffected by treatment with TLR4 antagonists, a blocking IgG or a TLR4 analog antagonist, suggesting that UVR cell death is independent of a soluble ligand. After UVR, IRAK4KDKI (catalytically inactive IRAK4) and wild-type (WT) macrophages show equivalent levels of survival, as measured by MTT assay, and apoptosis, as measured by cleaved caspase-3. Furthermore, in macrophages from both mice, UVR activated caspase-8 and PARP, while inactivating Rip3. This finding is supported by a lack of IRAK1 degradation after UVR, compared to treatment with TLR2 or TLR4 agonists. UVR induced association of MyD88 with FADD, an extrinsic apoptotic pathway protein, but not IRAK4. UVR-induced migration of FADD to the cell membrane of WT macrophages, but not MyD88-/- macrophages, was observed (confocal microscopy). Co immunoprecipitation using an epitope-tagged MyD88 revealed that FADD, but not TRADD, was recruited to MyD88 within 30 minutes of UVR exposure. UVR engages TLR4/MyD88 as a death signalling complex, rather than the classical inflammatory signalling pathway triggered by PAMP recognition of TLR4. These studies provide the rationale for the future development of topical TLR4 modulating therapies to interfere with this UVB-mediated apoptosis and the associated negative consequences of immune suppression. PMID- 27676215 TI - Super-elastic and fatigue resistant carbon material with lamellar multi-arch microstructure. AB - Low-density compressible materials enable various applications but are often hindered by structure-derived fatigue failure, weak elasticity with slow recovery speed and large energy dissipation. Here we demonstrate a carbon material with microstructure-derived super-elasticity and high fatigue resistance achieved by designing a hierarchical lamellar architecture composed of thousands of microscale arches that serve as elastic units. The obtained monolithic carbon material can rebound a steel ball in spring-like fashion with fast recovery speed (~580 mm s-1), and demonstrates complete recovery and small energy dissipation (~0.2) in each compress-release cycle, even under 90% strain. Particularly, the material can maintain structural integrity after more than 106 cycles at 20% strain and 2.5 * 105 cycles at 50% strain. This structural material, although constructed using an intrinsically brittle carbon constituent, is simultaneously super-elastic, highly compressible and fatigue resistant to a degree even greater than that of previously reported compressible foams mainly made from more robust constituents. PMID- 27676216 TI - A review of surface wipe sampling compared to biologic monitoring for occupational exposure to antineoplastic drugs. AB - The potential for adverse health effects from occupational exposure to antineoplastic drugs (AD) is well known. Control measures recommended by the NIOSH Alert [3] include medical and biologic monitoring, and environmental monitoring where available. At present no guidelines or published best practices exist to guide EHS managers on how to carry out this biologic or environmental monitoring. Studies investigating surface wipe sampling for AD have been numerous in the past decade, but very limited research exists to correlate surface contamination with actual absorption by pharmacists and nurses. This article reviews the studies with concurrent surface wipe sampling and urine monitoring for the same AD, and tests their correlation. Methodologic limitations are reviewed. Twenty-one studies were identified that concurrently measured surface contamination by AD by wipe sampling and AD absorption by urine monitoring. Two studies directly evaluated the AD by wipe sampling and urine levels and neither found a statistically significant correlation. Six studies reported a decrease in both surface and urine levels following interventions to reduce contamination or exposure. Only one study directly evaluated the personal protective equipment and handling techniques employed by the studied workers, which can be viewed as a major confounder of absorption. While no statistically significant correlation was found between wipe sampling and urine monitoring for AD, decreases in urine and wipe levels following interventions to reduce exposure were noted. Limitations in the data and recommendations for future research are reviewed. PMID- 27676217 TI - Long-term data set of small mammals from owl pellets in the Atlantic Mediterranean transition area. AB - We describe the pellet sampling data set from the Vertebrate Collection of the Museum of Zoology of the University of Navarra. This data set compiles all information about small mammals obtained from the analysis of owl pellets. The collection consists on skulls, mandibles, and some skeletons of 36 species of more than 72,000 georeferenced specimens. These specimens come from the Iberian Peninsula although most samples were collected in Navarra, a highly diverse transitional area of 10,000 kilometre square sitting across three biogeographical regions. The collection spans more than forty years and is still growing as a result of the establishment of a barn owl pellet monitoring network in 2015. The program will provide critical information about the evolution of the small mammals' community in this transition zone as it changes over time. PMID- 27676218 TI - Corrigendum: Muropeptides in Pseudomonas aeruginosa and their Role as Elicitors of beta-Lactam-Antibiotic Resistance. PMID- 27676220 TI - The effects of emotion on younger and older adults' monitoring of learning. AB - Age-related differences in memory monitoring appear when people learn emotional words. Namely, younger adults' judgments of learning (JOLs) are higher for positive than neutral words, whereas older adults' JOLs do not discriminate between positive versus neutral words. In two experiments, we evaluated whether this age-related difference extends to learning positive versus neutral pictures. We also evaluated the contribution of two dimensions of emotion that may impact younger and older adults' JOLs: valence and arousal. Younger and older adults studied pictures that were positive or neutral and either high or low in arousal. Participants made immediate JOLs and completed memory tests. In both experiments, the magnitude of older adults' JOLs was influenced by emotion, and both younger and older adults demonstrated an emotional salience effect on JOLs. As important, the magnitude of participants' JOLs was influenced by valence, and not arousal. Emotional salience effects were also evident on participants' free recall, and older adults recalled as many pictures as did younger adults. Taken together, these data suggest that older adults do not have a monitoring deficit when learning positive (vs. neutral) pictures and that emotional salience effects on younger and older adults' JOLs are produced more by valence than by arousal. PMID- 27676222 TI - Orientation Control of Smectic Liquid Crystals via a Combination Method of Topographic Patterning and In-Plane Electric Field Application for a Linearly Polarized Illuminator. AB - We dynamically controlled the configuration of layering structures built by smectic A liquid crystal molecules using the combination method of the microchannel confinement and the in-plane electric field to realize the linearly polarized illuminator and bistable structures. Once a mild in-plane electric field (~30 V) is applied between polymeric walls, the layer configuration was changed from the toric focal conic domains to periodic zigzag patterns of alternatively packed focal conic domains. The transformed zigzag patterns maintained their structures even after turning off the applied electric fields, revealing the ability for use in a bistable memory device. Indeed, a strong electric field (~100 V) can make unidirectionally aligned LC molecules along with the applied electric field via zigzag patterns, and electro-optical performance of resultant textures when the sample is mixed with fluorescent dyes was characterized to show a linearly polarized light illuminator. Our electric field in and on the confined geometries will be used in the fabrication of functional structures built by polar soft materials which can broaden applications in patterning platforms and efficient electro-optical devices in the near future. PMID- 27676221 TI - Detection of Mild Traumatic Brain Injury by Machine Learning Classification Using Resting State Functional Network Connectivity and Fractional Anisotropy. AB - Traumatic brain injury (TBI) may adversely affect a person's thinking, memory, personality, and behavior. While mild TBI (mTBI) diagnosis is challenging, there is a risk for long-term psychiatric, neurologic, and psychosocial problems in some patients that motivates the search for new and better biomarkers. Recently, diffusion magnetic resonance imaging (dMRI) has shown promise in detecting mTBI, but its validity is still being investigated. Resting state functional network connectivity (rsFNC) is another approach that is emerging as a promising option for the diagnosis of mTBI. The present work investigated the use of rsFNC for mTBI detection compared with dMRI results on the same cohort. Fifty patients with mTBI (25 males) and age-sex matched healthy controls were recruited. Features from dMRI were obtained using all voxels, the enhanced Z-score microstructural assessment for pathology, and the distribution corrected Z-score. Features based on rsFNC were obtained through group independent component analysis and correlation between pairs of resting state networks. A linear support vector machine was used for classification and validated using leave-one-out cross validation. Classification achieved a maximum accuracy of 84.1% for rsFNC and 75.5% for dMRI and 74.5% for both combined. A t test analysis revealed significant increase in rsFNC between cerebellum versus sensorimotor networks and between left angular gyrus versus precuneus in subjects with mTBI. These outcomes suggest that inclusion of both common and unique information is important for classification of mTBI. Results also suggest that rsFNC can yield viable biomarkers that might outperform dMRI and points to connectivity to the cerebellum as an important region for the detection of mTBI. PMID- 27676223 TI - Current Physical Activity Is Independently Associated With Cortical Bone Size and Bone Strength in Elderly Swedish Women. AB - Physical activity is believed to have the greatest effect on the skeleton if exerted early in life, but whether or not possible benefits of physical activity on bone microstructure or geometry remain at old age has not been investigated in women. The aim of this study was to investigate if physical activity during skeletal growth and young adulthood or at old age was associated with cortical geometry and trabecular microarchitecture in weight-bearing and non-weight bearing bone, and areal bone mineral density (aBMD) in elderly women. In this population-based cross-sectional study 1013 women, 78.2 +/- 1.6 (mean +/- SD) years old, were included. Using high-resolution 3D pQCT (XtremeCT), cortical cross-sectional area (Ct.CSA), cortical thickness (Ct.Th), cortical periosteal perimeter (Ct.Pm), volumetric cortical bone density (D.Ct), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were measured at the distal (14% level) and ultra-distal tibia and radius, respectively. aBMD was assessed using DXA (Hologic Discovery A) of the spine and hip. A standardized questionnaire was used to collect information about previous exercise and the Physical Activity Scale for the Elderly (PASE) was used for current physical activity. A linear regression model (including levels of exercise during skeletal growth and young adulthood [10 to 30 years of age], PASE score, and covariates) revealed that level of current physical activity was independently associated with Ct.CSA (beta = 0.18, p < 0.001) and Ct.Th (beta = 0.15, p < 0.001) at the distal tibia, Tb.Th (beta = 0.11, p < 0.001) and BV/TV (beta = 0.10, p = 0.001) at the ultra-distal tibia, and total hip aBMD (beta = 0.10, p < 0.001). Current physical activity was independently associated with cortical bone size, in terms of thicker cortex but not larger periosteal circumference, and higher bone strength at the distal tibia on elderly women, indicating that physical activity at old age may decrease cortical bone loss in weight-bearing bone in elderly women. (c) 2016 American Society for Bone and Mineral Research. PMID- 27676225 TI - Introduction to Special Issue on Air Pollution Health Risks. PMID- 27676224 TI - Structure-Activity Relationships of the MEPicides: N-Acyl and O-Linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis. AB - Despite continued research efforts, the threat of drug resistance from a variety of bacteria continues to plague clinical communities. Discovery and validation of novel biochemical targets will facilitate development of new drugs to combat these organisms. The methylerythritol phosphate (MEP) pathway to make isoprene units is a biosynthetic pathway essential to many bacteria. We and others have explored inhibitors of the MEP pathway as novel antibacterial agents. Mycobacterium tuberculosis, the causative agent of tuberculosis, and Yersinia pestis, resulting in the plague or "black death", both rely on the MEP pathway for isoprene production. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr) catalyzes the first committed step in the MEP pathway. We examined two series of Dxr inhibitors based on the parent structure of the retrohydroxamate natural product FR900098. The compounds contain either an extended N-acyl or O-linked alkyl/aryl group and are designed to act as bisubstrate inhibitors of the enzyme. While nearly all of the compounds inhibited both Mtb and Yp Dxr to some extent, compounds generally displayed more potent inhibition against the Yp homologue, with the best analogs displaying nanomolar IC50 values. In bacterial growth inhibition assays, the phosphonic acids generally resulted in poor antibacterial activity, likely a reflection of inadequate permeability. Accordingly, diethyl and dipivaloyloxymethyl (POM) prodrug esters of these compounds were made. While the added lipophilicity did not enhance Yersinia activity, the compounds showed significantly improved antitubercular activities. The most potent compounds have Mtb MIC values of 3-12 MUg/mL. Taken together, we have uncovered two series of analogs that potently inhibit Dxr homologues from Mtb and Yp. These inhibitors of the MEP pathway, termed MEPicides, serve as leads for future analog development. PMID- 27676227 TI - Spatial Risk Analysis of Hydraulic Fracturing near Abandoned and Converted Oil and Gas Wells. AB - Interaction between hydraulically generated fractures and existing wells (frac hits) could represent a potential risk to groundwater. In particular, frac hits on abandoned oil and gas wells could lead to upward leakage into overlying aquifers, provided migration pathways are present along the abandoned well. However, potential risk to groundwater is relatively unknown because few studies have investigated the probability of frac hits on abandoned wells. In this study, actual numbers of frac hits were not determined. Rather, the probability for abandoned wells to intersect hypothetical stimulated reservoir sizes of horizontal wells was investigated. Well data were compiled and analyzed for location and reservoir information, and sensitivity analyses were conducted by varying assumed sizes of stimulated reservoirs. This study used public and industry data for the Eagle Ford Shale play in south Texas, with specific attention paid to abandoned oil and gas wells converted into water wells (converted wells). In counties with Eagle Ford Shale activity, well-data analysis identified 55,720 abandoned wells with a median age of 1983, and 2400 converted wells with a median age of 1954. The most aggressive scenario resulted in 823 abandoned wells and 184 converted wells intersecting the largest assumed stimulated reservoir size. Analysis showed abandoned wells have the potential to be intersected by multiple stimulated reservoirs, and risks for intersection would increase if currently permitted horizontal wells in the Eagle Ford Shale are actually completed. Results underscore the need to evaluate historical oil and gas activities in areas with modern unconventional oil and gas activities. PMID- 27676228 TI - High-Pressure Reactivity of Triptycene Probed by Raman Spectroscopy. AB - The high-pressure reactivity of caged olefinic carbons and polyatomic aromatic hydrocarbons (PAHs) are of interest because of their ability to produce unique C H networks with varying geometries and bonding environments. Here, we have selected triptycene to explore the creation of pores via high-pressure polymerization. Triptycene has internal free volume on a molecular scale that arises due to its paddle wheel-like structure, formed via fusion of three benzene rings via sp3-hybridized bridgehead carbon sites. At 25 GPa and 298 K, triptycene polymerizes to yield an amorphous hydrogenated carbon, with FTIR indicating an sp3 C-H content of approximately 40%. Vibrational spectroscopy conclusively demonstrates that triptycene polymerizes via cycloaddition reactions at the aromatic sites via a ring opening mechanism. The bridgehead carbons remain intact after polymerization, indicating the rigid backbone of the triptycene precursor is retained in the polymer, as well as molecular-level (~1-3 A) internal free volume. High resolution transmission electron microscopy, combined with dark field imaging, indicates the presence of ~10 nm voids in the polymer, which we attribute to either polymeric clustering or a hierarchical tertiary porous network. Creation of a polymerized network that retains internal voids via high pressure polymerization is attributed to the presence and retention of the bridgehead carbons. PMID- 27676226 TI - Pattern and Predictors of Hospital Readmission During the First Year After Lung Transplantation. AB - Hospital readmission after lung transplantation negatively affects quality of life and resource utilization. A secondary analysis of data collected prospectively was conducted to identify the pattern of (incidence, count, cumulative duration), reasons for and predictors of readmission for 201 lung transplant recipients (LTRs) assessed at 2, 6, and 12 mo after discharge. The majority of LTRs (83.6%) were readmitted, and 64.2% had multiple readmissions. The median cumulative readmission duration was 19 days. The main reasons for readmission were other than infection or rejection (55.5%), infection only (25.4%), rejection only (9.9%), and infection and rejection (0.7%). LTRs who required reintubation (odds ratio [OR] 1.92; p = 0.008) or were discharged to care facilities (OR 2.78; p = 0.008) were at higher risk for readmission, with a 95.7% cumulative incidence of readmission at 12 mo. Thirty-day readmission (40.8%) was not significantly predicted by baseline characteristics. Predictors of higher readmission count were lower capacity to engage in self-care (incidence rate ratio [IRR] 0.99; p = 0.03) and discharge to care facilities (IRR 1.45; p = 0.01). Predictors of longer cumulative readmission duration were older age (arithmetic mean ratio [AMR] 1.02; p = 0.009), return to the intensive care unit (AMR 2.00; p = 0.01) and lower capacity to engage in self-care (AMR 0.99; p = 0.03). Identifying LTRs at risk may assist in optimizing predischarge care, discharge planning and long-term follow-up. PMID- 27676230 TI - ERRATUM. PMID- 27676229 TI - Lessons in Andrology. PMID- 27676232 TI - Nurses' Use of Race in Clinical Decision Making. AB - PURPOSE: To examine nurses' self-reported use of race in clinical evaluation. DESIGN: This cross-sectional study analyzed data collected from three separate studies using the Genetics and Genomics in Nursing Practice Survey, which includes items about use of race and genomic information in nursing practice. The Racial Attributes in Clinical Evaluation (RACE) scale was used to measure explicit clinical use of race among nurses from across the United States. METHODS: Multivariate regression analysis was used to examine associations between RACE score and individual-level characteristics and beliefs in 5,733 registered nurses. FINDINGS: Analysis revealed significant relationships between RACE score and nurses' race and ethnicity, educational level, and views on the clinical importance of patient demographic characteristics. Asian nurses reported RACE scores 1.41 points higher than White nurses (p < .001), and Black nurses reported RACE scores 0.55 points higher than White nurses (p < .05). Compared to diploma-level nurses, the baccalaureate-level nurses reported 0.69 points higher RACE scores (p < .05), master's-level nurses reported 1.63 points higher RACE scores (p < .001), and doctorate-level nurses reported 1.77 points higher RACE scores (p < .01). In terms of clinical importance of patient characteristics, patient race and ethnicity corresponded to a 0.54-point increase in RACE score (p < .001), patient genes to a 0.21-point increase in RACE score (p < .001), patient family history to a 0.15-point increase in RACE score (p < .01), and patient age to a 0.19-point increase in RACE score (p < .001). CONCLUSIONS: Higher reported use of race among minority nurses may be due, in part, to differential levels of racial self-awareness. A relatively linear positive relationship between level of nursing degree nursing education and use of race suggests that a stronger foundation of knowledge about genetic ancestry, population genetics and the concept "race" and genetic ancestry may increase in clinical decision making could allow nurses to more appropriately use of race in clinical care. Integrating patient demographic characteristics into clinical decisions is an important component of nursing practice. CLINICAL RELEVANCE: Registered nurses provide care for diverse racial and ethnic patient populations and stand on the front line of clinical care, making them essential for reducing racial and ethnic disparities in healthcare delivery. Exploring registered nurses' individual-level characteristics and clinical use of race may provide a more comprehensive understanding of specific training needs and inform nursing education and practice. PMID- 27676233 TI - Leptin modifies the prosecretory and prokinetic effects of the inflammatory cytokine interleukin-6 on colonic function in Sprague-Dawley rats. AB - NEW FINDINGS: What is the central question of this study? Does crosstalk exist between leptin and interleukin-6 in colonic enteric neurons, and is this a contributory factor in gastrointestinal dysfunction associated with irritable bowel syndrome? What is the main finding and its importance? Leptin ameliorates the prosecretory and prokinetic effects of the pro-inflammatory cytokine interleukin-6 on rat colon. Leptin also suppresses the neurostimulatory effects of irritable bowel syndrome plasma, which has elevated concentrations of interleukin-6, on enteric neurons. This may indicate a regulatory role for leptin in immune-mediated bowel dysfunction. In addition to its role in regulating energy homeostasis, the adipokine leptin modifies gastrointestinal (GI) function. Indeed, leptin-resistant obese humans and leptin-deficient obese mice exhibit altered GI motility. In the functional GI disorder irritable bowel syndrome (IBS), circulating leptin concentrations are reported to differ from those of healthy control subjects. Additionally, IBS patients display altered cytokine profiles, including elevated circulating concentrations of the pro-inflammatory cytokine interleukin-6 (IL-6), which bears structural homology and similarities in intracellular signalling to leptin. This study aimed to investigate interactions between leptin and IL-6 in colonic neurons and their possible contribution to IBS pathophysiology. The functional effects of leptin and IL-6 on colonic contractility and absorptosecretory function were assessed in organ baths and Ussing chambers in Sprague-Dawley rat colon. Calcium imaging and immunohistochemical techniques were used to investigate the neural regulation of GI function by these signalling molecules. Our findings provide a neuromodulatory role for leptin in submucosal neurons, where it inhibited the stimulatory effects of IL-6. Functionally, this translated to suppression of IL-6-evoked potentiation of veratridine-induced secretory currents. Leptin also attenuated IL-6-induced colonic contractions, although it had little direct effect on myenteric neurons. Calcium responses evoked by IBS plasma in both myenteric and submucosal neurons were also suppressed by leptin, possibly through interactions with IL-6, which is elevated in IBS plasma. As leptin has the capacity to ameliorate the neurostimulatory effects of soluble mediators in IBS plasma and modulated IL-6 evoked changes in bowel function, leptin may have a role in immune-mediated bowel dysfunction in IBS patients. PMID- 27676234 TI - Comparative evaluation of a heparin-citrate anticoagulation for LDL-apheresis in two primary apheresis systems. AB - BACKGROUND: As COBE Spectra has been replaced in many parts of the world, we describe a new protocol for low-density lipoprotein (LDL)-apheresis performed on familial hypercholesterolemia patients for the Spectra Optia platform. METHODS: For all procedures, after administering a bolus of heparin of 2,500 U, 10,000 U of heparin added to a 600 ml ACD-A bag was used as anticoagulant (AC). In a first phase (A), 16 apheresis procedures with COBE Spectra using an inlet:AC ratio of 25:1 were compared to 18 LDL-apheresis treatments with Spectra Optia at split Inlet:AC ratios of 16:1/18:1 or 20:1/25:1. Platelet activation and coagulation markers were assessed. In a follow-up phase (B), 20 procedures on Spectra Optia using an inlet:AC ratio of 20:1 were performed. RESULTS: Although coagulation markers and platelet activation analyzed were similar in both apheresis devices used, COBE Spectra procedures did not show any visual clumping in the sets. Visual analysis of clumping was highest in the Spectra Optia's 20:1/25:1 AC regimen (5/8 procedures). For the lowest Spectra Optia, AC regimen and during the follow-up phase reversible clump formation in the disposable set was similar (1/10 procedures). Clumping was successfully reversed in all cases by temporarily lowering the inlet:AC ratio to 18:1. Blood cell counts (WBC, Plt, Hct) were similar for both COBE Spectra and Spectra Optia procedures. Spectra Optia had a significantly higher plasma removal efficiency versus COBE Spectra (84% vs.75%, P < .05). No serious adverse events were observed. CONCLUSION: Apheresis procedures on the Spectra Optia system with low-dose heparin-citrate anticoagulation are feasible and safe. PMID- 27676235 TI - A Water-Stable Metal-Organic Framework for Highly Sensitive and Selective Sensing of Fe3+ Ion. AB - A new metal-organic framework [Zn5(hfipbb)4(trz)2(H2O)2] (NNU-1) [H2hfipbb = 4,4' (hexafluoroisopropylidene)bis(benzoic acid), Htrz = 1H-1,2,3-triazole] was assembled by hydrothermal synthesis. Single-crystal X-ray diffraction analysis reveals that NNU-1 displays a twofold interpenetrating three-dimensional (3D) framework with a {424.64}-bcu topology. Interestingly, the 3D framework contains a two-dimensional (2D) layered structure that consists of alternating left- and right-handed double helical chains. On the basis of the hydrophobic -CF3 groups from H2hfipbb ligand, NNU-1 possesses excellent stability in water. It is worth noting that NNU-1 not only shows a highly selective fluorescence quenching effect to Fe3+ ion in aqueous solution but also resists the interference of other metals including Fe2+ ion. Accordingly, NNU-1 probably functions as a potential promising fluorescence sensor for detecting Fe3+ ion with high sensitivity and selectivity. PMID- 27676237 TI - An Interim Analysis of an Advance Care Planning Intervention in the Nursing Home Setting. AB - OBJECTIVES: To describe processes and preliminary outcomes from the implementation of a systematic advance care planning (ACP) intervention in the nursing home setting. DESIGN: Specially trained project nurses were embedded in 19 nursing homes and engaged in ACP as part of larger demonstration project to reduce potentially avoidable hospitalizations. SETTING: Nursing homes. PARTICIPANTS: Residents enrolled in the demonstration project for a minimum of 30 days between August 2013 and December 2014 (n = 2,709) and residents currently enrolled in March 2015 (n = 1,591). MEASUREMENTS: ACP conversations were conducted with residents, families, and the legal representatives of incapacitated residents using a structured ACP interview guide with the goal of offering ACP to all residents. Project nurses reviewed their roster of currently enrolled residents in March 2015 to capture barriers to engaging in ACP. RESULTS: During the initial implementation phase, 27% (731/2,709) of residents had participated in one or more ACP conversations with a project nurse, resulting in a change in documented treatment preferences for 69% (504/731). The most common change (87%) was the generation of a Physician Orders for Scope of Treatment form. The most frequently reported barrier to ACP was lack of time. CONCLUSION: The time- and resource-intensive nature of robust ACP must be anticipated when systematically implementing ACP in the nursing home setting. The fact that these conversations resulted in changes over 2/3 of the time reinforces the importance of deliberate, systematic ACP to ensure that current treatment preferences are known and documented so that these preferences can be honored. PMID- 27676238 TI - Oxidative DNA Damage and Repair in the Radioresistant Archaeon Thermococcus gammatolerans. AB - The hyperthermophilic archaeon Thermococcus gammatolerans can resist huge doses of gamma-irradiation, up to 5.0 kGy, without loss of viability. The potential to withstand such harsh conditions is probably due to complementary passive and active mechanisms, including repair of damaged chromosomes. In this work, we documented the formation and repair of oxidative DNA lesions in T. gammatolerans. The basal level of the oxidized nucleoside, 8-oxo-2'-deoxyguanosine (8-oxo-dGuo), was established at 9.2 (+/- 0.9) 8-oxo-dGuo per 106 nucleosides, a higher level than those usually measured in eukaryotic cells or bacteria. A significant increase in oxidative damage, i.e., up to 24.2 (+/- 8.0) 8-oxo-dGuo/106 nucleosides, was measured for T. gammatolerans exposed to a 5.0 kGy dose of gamma rays. Surprisingly, the yield of radiation-induced modifications was lower than those previously observed for human cells exposed to doses corresponding to a few grays. One hour after irradiation, 8-oxo-dGuo levels were significantly reduced, indicating an efficient repair. Two putative base excision repair (BER) enzymes, TGAM_1277 and TGAM_1653, were demonstrated both by proteomics and transcriptomics to be present in the cells without exposure to ionizing radiation. Their transcripts were moderately upregulated after gamma irradiation. After heterologous production and purification of these enzymes, biochemical assays based on electrophoresis and MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectrometry indicated that both have a beta elimination cleavage activity. TGAM_1653 repairs 8-oxo-dGuo, whereas TGAM_1277 is also able to remove lesions affecting pyrimidines (1-[2-deoxy-beta-d-erythro pentofuranosyl]-5-hydroxyhydantoin (5-OH-dHyd) and 1-[2-deoxy-beta-d-erythro pentofuranosyl]-5-hydroxy-5-methylhydantoin (5-OH-5-Me-dHyd)). This work showed that in normal growth conditions or in the presence of a strong oxidative stress, T. gammatolerans has the potential to rapidly reduce the extent of DNA oxidation, with at least these two BER enzymes as bodyguards with distinct substrate ranges. PMID- 27676239 TI - Structural insight into the necessary conformational changes of modular nonribosomal peptide synthetases. AB - Nonribosomal peptide synthetases (NRPSs) catalyze the assembly line biosynthesis of peptide natural products that play important roles in microbial signaling and communication. These multidomain enzymes use an integrated carrier protein that delivers the growing peptide to the catalytic domains, requiring coordinated conformational changes that allow the proper sequence of synthetic steps. Recent structural studies of NRPSs have described important conformational states and illustrate the critical role of a small subdomain within the adenylation domains. This subdomain alternates between catalytic conformations and also serves as a linker domain, providing further conformational flexibility to enable the carrier to project from the core of NRPS. These studies are described along with remaining questions in the study of the structural dynamics of NRPSs. PMID- 27676241 TI - Freight-train derailment rates for railroad safety and risk analysis. AB - Derailments are the most common type of train accident in the United States. They cause damage to infrastructure, rolling stock and lading, disrupt service, and have the potential to cause casualties, and harm the environment. Train safety and risk analysis relies on accurate assessment of derailment likelihood. Derailment rate - the number of derailments normalized by traffic exposure - is a useful statistic to estimate the likelihood of a derailment. Despite its importance, derailment rate analysis using multiple factors has not been previously developed. In this paper, we present an analysis of derailment rates on Class I railroad mainlines based on data from the U.S. Federal Railroad Administration and the major freight railroads. The point estimator and confidence interval of train and car derailment rates are developed by FRA track class, method of operation and annual traffic density. The analysis shows that signaled track with higher FRA track class and higher traffic density is associated with a lower derailment rate. The new accident rates have important implications for safety and risk management decisions, such as the routing of hazardous materials. PMID- 27676240 TI - Energy Drink Use Patterns Among Young Adults: Associations with Drunk Driving. AB - BACKGROUND: Highly caffeinated "energy drinks" (ED) are commonly consumed and sometimes mixed with alcohol. Associations between ED consumption, risk-taking, and alcohol-related problems have been observed. This study examines the relationship between ED consumption-both with and without alcohol-and drunk driving. METHODS: Data were derived from a longitudinal study of college students assessed annually via personal interviews. In Year 6 (modal age 23; n = 1,000), participants self-reported their past-year frequency of drunk driving, ED consumption patterns (frequency of drinking alcohol mixed with energy drinks [AmED] and drinking energy drinks without alcohol [ED]), alcohol use (frequency, quantity), and other caffeine consumption. Earlier assessments captured suspected risk factors for drunk driving. Structural equation modeling was used to develop an explanatory model for the association between ED consumption patterns and drunk driving frequency while accounting for other suspected risk factors. RESULTS: More than half (57%) consumed ED at least once during the past year. Among ED consumers, 71% drank AmED and 85% drank ED alone; many (56%) engaged in both styles of ED consumption while others specialized in one or the other (29% drank ED alone exclusively, while, 15% drank AmED exclusively). After accounting for other risk factors, ED consumption was associated with drunk driving frequency in 2 ways. First, a direct path existed from ED frequency (without alcohol) to drunk driving frequency. Second, an indirect path existed from AmED frequency through alcohol quantity to drunk driving frequency. CONCLUSIONS: Among this sample, ED consumption with and without alcohol was common, and both styles of ED consumption contributed independently to drunk driving frequency. Results call for increased attention to the impact of different patterns of ED consumption on alcohol-related consequences, such as drunk driving. PMID- 27676242 TI - Speed behaviour in work zone crossovers. A driving simulator study. AB - Reductions in speed and, more critically, in speed variability between vehicles are considered an important factor to reduce crash risk in work zones. This study was designed to evaluate in a virtual environment the drivers' behaviour in response to nine different configurations of a motorway crossover work zone. Specifically, the speed behaviour through a typical crossover layout, designed in accordance with the Italian Ministerial Decree 10 July 2002, was compared with that of eight alternative configurations which differ in some characteristics such as the sequence of speed limits, the median opening width and the lane width. The influence of variable message signs, of channelizing devices and of perceptual treatments based on Human Factor principles were also tested. Forty two participants drove in driving simulator scenarios while data on their speeds and decelerations were collected. The results indicated that drivers' speeds are always higher than the temporary posted speed limits for all configurations and that speeds decreases significantly only within the by-passes. However the implementation of higher speed limits, together with a wider median opening and taller channelization devices led to a greater homogeneity of the speeds adopted by the drivers. The presence of perceptual measures generally induced both the greatest homogenization of speeds and the largest reductions in mean speed values. PMID- 27676243 TI - Rate Coefficients of the Reaction of OH with Allene and Propyne at High Temperatures. AB - Allene (H2C?C?CH2; a-C3H4) and propyne (CH3C=CH; p-C3H4) are important species in various chemical environments. In combustion processes, the reactions of hydroxyl radicals with a-C3H4 and p-C3H4 are critical in the overall fuel oxidation system. In this work, rate coefficients of OH radicals with allene (OH + H2C?C?CH2 -> products) and propyne (OH + CH3C=CH -> products) were measured behind reflected shock waves over the temperature range of 843-1352 K and pressures near 1.5 atm. Hydroxyl radicals were generated by rapid thermal decomposition of tert-butyl hydroperoxide ((CH3)3-CO-OH), and monitored by narrow line width laser absorption of the well-characterized R1(5) electronic transition of the OH A-X (0,0) electronic system near 306.7 nm. Results show that allene reacts faster with OH radicals than propyne over the temperature range of this study. Measured rate coefficients can be expressed in Arrhenius form as follows: kallene+OH(T) = 8.51(+/-0.03) * 10-22T3.05 exp(2215(+/-3)/T), T = 843-1352 K; kpropyne+OH(T) = 1.30(+/-0.07) * 10-21T3.01 exp(1140(+/-6)/T), T = 846-1335 K. PMID- 27676244 TI - 2D Covalent Metals: A New Materials Domain of Electrochemical CO2 Conversion with Broken Scaling Relationship. AB - Toward a sustainable carbon cycle, electrochemical conversion of CO2 into valuable fuels has drawn much attention. However, sluggish kinetics and a substantial overpotential, originating from the strong correlation between the adsorption energies of intermediates and products, are key obstacles of electrochemical CO2 conversion. Here we show that 2D covalent metals with a zero band gap can overcome the intrinsic limitation of conventional metals and metal alloys and thereby substantially decrease the overpotential for CO2 reduction because of their covalent characteristics. From first-principles-based high throughput screening results on 61 2D covalent metals, we find that the strong correlation between the adsorption energies of COOH and CO can be entirely broken. This leads to the computational design of CO2-to-CO and CO2-to-CH4 conversion catalysts in addition to hydrogen-evolution-reaction catalysts. Toward efficient electrochemical catalysts for CO2 reduction, this work suggests a new materials domain having two contradictory properties in a single material: covalent nature and electrical conductance. PMID- 27676245 TI - Subcellular location of Arabidopsis thaliana subfamily a1 beta-galactosidases and developmental regulation of transcript levels of their coding genes. AB - The aim of this work is to gain insight into the six members of the a1 subfamily of the beta-galactosidases (BGAL) from Arabidopsis thaliana. First, the subcellular location of all these six BGAL proteins from a1 subfamily has been established in the cell wall by the construction of transgenic plants producing the enhanced green fluorescent protein (eGFP) fused to the BGAL proteins. BGAL12 is also located in the endoplasmic reticulum. Our study of the AtBGAL transcript accumulation along plant development indicated that all AtBGAL transcript appeared in initial stages of development, both dark- and light-grown seedlings, being AtBGAL1, AtBGAL2 and AtBGAL3 transcripts the predominant ones in the latter condition, mainly in the aerial part and with levels decreasing with age. The high accumulation of transcript of AtBGAL4 in basal internodes and in leaves at the end of development, and their strong increase after treatment both with BL and H3BO3 point to an involvement of BGAL4 in cell wall changes leading to the cease of elongation and increased rigidity. The changes of AtBGAL transcript accumulation in relation to different stages and conditions of plant development, suggest that each of the different gene products have a plant-specific function and provides support for the proposed function of the subfamily a1 BGAL in plant cell wall remodelling for cell expansion or for cell response to stress conditions. PMID- 27676247 TI - A Novel Approach to Proactive Primary Care-Based Case Finding and Multidisciplinary Management of Falls, Syncope, and Dizziness in a One-Stop Service: Preliminary Results. AB - National and international evidence and guidelines on falls prevention and management in community-dwelling elderly adults recommend that falls services should be multifactorial and their interventions multicomponent. The way that individuals are identified as having had or being at risk of falls in order to take advantage of such services is far less clear. A novel multidisciplinary, multifactorial falls, syncope, and dizziness service model was designed with enhanced case ascertainment through proactive, primary care-based screening (of individual case notes of individuals aged >=60) for individual fall risk factors. The service model identified 4,039 individuals, of whom 2,232 had significant gait and balance abnormalities according to senior physiotherapist assessment. Significant numbers of individuals with new diagnoses ranging from cognitive impairment to Parkinson's disease to urgent indications for a pacemaker were discovered. More than 600 individuals were found who were at high risk of osteoporosis according to World Health Association Fracture Risk Assessment Tool score, 179 with benign positional paroxysmal vertigo and 50 with atrial fibrillation. Through such screening and this approach, Comprehensive Geriatric Assessment Plus (Plus falls, syncope and dizziness expertise), unmet need was targeted on a scale far outside the numbers seen in clinical trials. Further work is needed to determine whether this approach translates into fewer falls and decreases in syncope and dizziness. PMID- 27676246 TI - A Comprehensive Functional Analysis of NTRK1 Missense Mutations Causing Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN IV). AB - Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is an autosomal recessive disorder characterized by a complete lack of pain perception and anhidrosis. Here, we studied a cohort of seven patients with HSAN IV and describe a comprehensive functional analysis of seven novel NTRK1 missense mutations, c.1550G >A, c.1565G >A, c.1970T >C, c.2096T >C, c.2254T >A, c.2288G >C, and c.2311C >T, corresponding to p.G517E, p.G522E, p.L657P, p.I699T, p.C752S, p.C763S, and p.R771C, all of which were predicted pathogenic by in silico analysis. The results allowed us to assess the pathogenicity of each mutation and to gain novel insights into tropomyosin receptor kinase A (TRKA) downstream signaling. Each mutation was systematically analyzed for TRKA glycosylation states, intracellular and cell membrane expression patterns, nerve growth factor stimulated TRKA autophosphorylation, TRKA-Y496 phosphorylation, PLCgamma activity, and neurite outgrowth. We showed a diverse range of functional effects: one mutation appeared fully functional, another had partial activity in all assays, one mutation affected only the PLCgamma pathway and four mutations were proved null in all assays. Thus, we conclude that complete abolition of TRKA kinase activity is not the only pathogenic mechanism underlying HSAN IV. By corollary, the assessment of the clinical pathogenicity of HSAN IV mutations is more complex than initially predicted and requires a multifaceted approach. PMID- 27676248 TI - Exploring perinatal death with midwifery students' using a collaborative art project. AB - OBJECTIVE: To explore the influence of the Amulet artwork and exhibition on midwifery students' perceptions of caring for parents experiencing perinatal death. DESIGN: A descriptive qualitative design involving face-to-face semi structured interviews following institutional ethical approval. SETTING: A regional Maternity Hospital in Ireland which hosted the National Artwork and Exhibition exploring the hidden world of infant death. PARTICIPANTS: A purposive sample of six consenting post registration midwifery students who had attended the Amulet artwork and exhibition. FINDINGS: Four core themes emerged and these were i) entering the mother's world and hearing her pain; ii) the journey of grief and connecting with the bereaved parent's unique experience; iii) facing the challenge of providing effective perinatal bereavement care; and iv) maintaining a journey of compassionate practice. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Exposure to, and reflection on the Amulet artwork and exhibition increased students' awareness and insight into the non-linear nature of the grieving process, and to the importance of maintaining a journey of compassionate care for parents experiencing perinatal death. The findings suggest that the use of creative women-centered strategies promote affective learning in relation to perinatal death and so may be of use to educators and maternity care providers. PMID- 27676250 TI - Iron-Catalyzed [2 + 2 + 2] Cycloaddition Reactions of Diynes with Oxyphosphaethynes To Construct 2-Phosphaphenol Derivatives. AB - Iron-catalyzed [2 + 2 + 2] cycloaddition reactions of diynes with siloxyphosphaethynes have been developed to give 2-phosphaphenol derivatives. The use of electronically neutral siloxyphosphaethynes generated in situ by the reaction of anionic phosphaethynolate with silyl triflates is key to achieving the reactions. PMID- 27676249 TI - A Bat-Derived Putative Cross-Family Recombinant Coronavirus with a Reovirus Gene. AB - The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3'-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution. PMID- 27676251 TI - Super-Anticoagulant Heparin-Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility. AB - In this study, heparin-mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb-like porous structure with well controlled thickness and show long-term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood related complement activation also confirm that the membranes exhibit super anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin-mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials. PMID- 27676252 TI - Beyond the French Flag Model: Exploiting Spatial and Gene Regulatory Interactions for Positional Information. AB - A crucial step in the early development of multicellular organisms involves the establishment of spatial patterns of gene expression which later direct proliferating cells to take on different cell fates. These patterns enable the cells to infer their global position within a tissue or an organism by reading out local gene expression levels. The patterning system is thus said to encode positional information, a concept that was formalized recently in the framework of information theory. Here we introduce a toy model of patterning in one spatial dimension, which can be seen as an extension of Wolpert's paradigmatic "French Flag" model, to patterning by several interacting, spatially coupled genes subject to intrinsic and extrinsic noise. Our model, a variant of an Ising spin system, allows us to systematically explore expression patterns that optimally encode positional information. We find that optimal patterning systems use positional cues, as in the French Flag model, together with gene-gene interactions to generate combinatorial codes for position which we call "Counter" patterns. Counter patterns can also be stabilized against noise and variations in system size or morphogen dosage by longer-range spatial interactions of the type invoked in the Turing model. The simple setup proposed here qualitatively captures many of the experimentally observed properties of biological patterning systems and allows them to be studied in a single, theoretically consistent framework. PMID- 27676253 TI - Residual thrombin potential predicts cardiovascular death in acute coronary syndrome patients undergoing percutaneous coronary intervention. AB - INTRODUCTION: Thrombin generation (TG) is a central step of the coagulation system involved in hemostatic and thrombotic roles. Scarce data evaluating in the acute phase the association between TG and the risk of cardiovascular death of acute coronary syndrome (ACS) patients are available, in the era of percutaneous coronary intervention (PCI) and stenting with the use of dual antiplatelet treatment. MATERIALS AND METHODS: We investigated TG in 292 ACS patients undergoing PCI with stent implantation on dual antiplatelet treatment. Venous samples were obtained 12-24h after PCI. TG was assessed using the Calibrated Automated Thrombogram (CAT). RESULTS: At two years of follow-up, 57 out of 292 patients (19.5%) died from cardiovascular causes. Higher values of endogenous thrombin potential (ETP) [1115.9 (705-1441.3) vs 940.2 (666.0-1253.1), p=0.049], peak [176.1 (80.5-259.4) vs 107.3 (59.9-181.1), p=0.002] and velocity index [61.75 (21.03-97.88) vs 25.64 (11.95-50.90), p<0.001] were observed in relation to survival patients. At the multivariate model adjusted for the Global Registry of Acute Coronary Events risk score, the association between TG and cardiovascular death remained significant for ETP [OR (95% CI): 2.58 (1.10-6.03), p=0.029], peak [OR (95%CI): 3.27 (1.35-7.92), p=0.009] and velocity index [OR (95% CI): 3.06 (1.27-7.39), p=0.013]. This result was confirmed after adjustment for high on-treatment platelet reactivity [ETP: OR (95% CI) 2.35 (1.11-5.00), p=0.027; peak: OR (95% CI) 2.42 (1.13-5.15), p=0.022; velocity index: OR (95% CI) 2.43 (1.14-5.20), p=0.022]. CONCLUSIONS: ACS patients with a residual TG after PCI and stent implantation have a significantly higher risk of long-term cardiovascular death. These results might be useful in improving risk stratification for ACS patients and support the need of a tailored antithrombotic therapy. PMID- 27676254 TI - Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in a cohort of patients with venous thromboembolism treated with vitamin K antagonists. AB - OBJECTIVE: The SAMe-TT2R2 score has been recently proposed to predict the quality of anticoagulation control in patients with atrial fibrillation treated with vitamin K antagonists (VKA). We aimed at calculating this score in a cohort of patients with Venous Thromboembolism (VTE) and determine its usefulness. METHODS: We included all consecutive patients with VTE treated with VKA for >90days. We collected all variables included in the score (female sex, age<60years, medical history [>2 comorbidities], treatment [interacting drugs: e.g. amiodarone], tobacco [doubled], race [doubled]) and analyzed the relationship between the SAMe TT2R2 score and time in therapeutic range (TTR), determined by the Rosendaal method and by the percentage of INR determinations (after excluding the first month). RESULTS: 135 patients were treated with VKA for >90days, with a median TTR 65%. No differences in INR controls within range were found between patients with score 0-1 vs >=2 (64.7+/-19.5% vs 66.0+/-20.5%, p=0.728). No differences were found in INR controls above (21.5+/-18.1% vs 21.2+/-21.3%, p=0.605) or below (3.9+/-14% vs 2.9+/-15.9%, p=0.517) the therapeutic range. CONCLUSION: The SAMe TT2R2 score is not useful to predict quality of anticoagulation control in patients with VTE treated with VKA. PMID- 27676255 TI - A novel mutation in the fibrinogen gamma-chain 216 Gly>Glu causes hypofibrinogenemia. PMID- 27676256 TI - Corrigendum to "Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays" [Thromb. Res. 139 (2016) 90-97]. PMID- 27676257 TI - Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption. AB - BACKGROUND: As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women. METHODS AND FINDINGS: We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748). The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT) for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1-2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h) after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. Of the 50 mother-infant pairs enrolled, 48% were <=12 wk and 52% were 13 24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22 28). During study follow-up, the median (IQR) daily reported frequency of infant breastfeeding was 15 times (12 to 18) overall, 16 (14 to 19) for the <=12 weeks, and 14 (12 to 17) for the 13-24 wk infant age groups. Overall, median (IQR) time averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7) for tenofovir and 212.5 ng/mL (140.0 to 405.0) for emtricitabine. Similarly, median (IQR) time-averaged trough concentrations in breast milk were 3.3 ng/mL (2.3 to 4.4) for tenofovir and 183.0 ng/mL (113.0 to 250.0) for emtricitabine, reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine, respectively. In infant plasma, tenofovir was unquantifiable in 46/49 samples (94%), but emtricitabine was detectable in 47/49 (96%) (median [IQR] concentration: 13.2 ng/mL [9.3 to 16.7]). The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 MUg/kg (IQR 0.35 to 0.71) for tenofovir and 31.9 MUg/kg (IQR 21.0 to 60.8) for emtricitabine, translating into a <0.01% and 0.5% relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection; a dose that has not shown safety concerns. No serious adverse effects were recorded during study follow-up. The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children. However, maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question. Importantly, there was minimal variation in breast milk concentrations of tenofovir and emtricitabine (respective median trough-to-peak concentration ratio ~1), demonstrating that infants were exposed to consistent drug dosing via breast milk. CONCLUSION: In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02776748. PMID- 27676258 TI - A Bone-Seeking trans-Cyclooctene for Pretargeting and Bioorthogonal Chemistry: A Proof of Concept Study Using 99mTc- and 177Lu-Labeled Tetrazines. AB - A high yield synthesis of a novel, small molecule, bisphosphonate-modified trans cyclooctene (TCO-BP, 2) that binds to regions of active bone metabolism and captures functionalized tetrazines in vivo, via the bioorthogonal inverse electron demand Diels-Alder (IEDDA) cycloaddition, was developed. A 99mTc-labeled derivative of 2 demonstrated selective localization to shoulder and knee joints in a biodistribution study in normal mice. Compound 2 reacted rapidly with a 177Lu-labeled tetrazine in vitro, and pretargeting experiments in mice, using 2 and the 177Lu-labeled tetrazine, yielded high activity concentrations in shoulder and knee joints, with minimal uptake in other tissues. Pretargeting experiments with 2 and a novel 99mTc-labeled tetrazine also produced high activity concentrations in the knees and shoulders. Critically, both radiolabeled tetrazines showed negligible uptake in the skeleton and joints when administered in the absence of 2. Compound 2 can be utilized to target functionalized tetrazines to bone and represents a convenient reagent to test novel tetrazines for use with in vivo bioorthogonal pretargeting strategies. PMID- 27676259 TI - Economic Feasibility of Staffing the Intensive Care Unit with a Communication Facilitator. AB - RATIONALE: In the intensive care unit (ICU), complex decision making by clinicians and families requires good communication to ensure that care is consistent with the patients' values and goals. OBJECTIVES: To assess the economic feasibility of staffing ICUs with a communication facilitator. METHODS: Data were from a randomized trial of an "ICU communication facilitator" linked to hospital financial records; eligible patients (n = 135) were admitted to the ICU at a single hospital with predicted mortality >=30% and a surrogate decision maker. Adjusted regression analyses assessed differences in ICU total and direct variable costs between intervention and control patients. A bootstrap-based simulation assessed the cost efficiency of a facilitator while varying the full time equivalent of the facilitator and the ICU mortality risk. MEASUREMENTS AND MAIN RESULTS: Total ICU costs (mean 22.8k; 95% CI, -42.0k to -3.6k; P = 0.02) and average daily ICU costs (mean, -0.38k; 95% CI, -0.65k to -0.11k; P = 0.006)] were reduced significantly with the intervention. Despite more contacts, families of survivors spent less time per encounter with facilitators than did families of decedents (mean, 25 [SD, 11] min vs. 36 [SD, 14] min). Simulation demonstrated maximal weekly savings with a 1.0 full-time equivalent facilitator and a predicted ICU mortality of 15% (total weekly ICU cost savings, $58.4k [95% CI, $57.7k-59.2k]; weekly direct variable savings, $5.7k [95% CI, $5.5k-5.8k]) after incorporating facilitator costs. CONCLUSIONS: Adding a full-time trained communication facilitator in the ICU may improve the quality of care while simultaneously reducing short-term (direct variable) and long-term (total) health care costs. This intervention is likely to be more cost effective in a lower mortality population. PMID- 27676260 TI - Collinearity and Causal Diagrams: A Lesson on the Importance of Model Specification. AB - BACKGROUND: Correlated data are ubiquitous in epidemiologic research, particularly in nutritional and environmental epidemiology where mixtures of factors are often studied. Our objectives are to demonstrate how highly correlated data arise in epidemiologic research and provide guidance, using a directed acyclic graph approach, on how to proceed analytically when faced with highly correlated data. METHODS: We identified three fundamental structural scenarios in which high correlation between a given variable and the exposure can arise: intermediates, confounders, and colliders. For each of these scenarios, we evaluated the consequences of increasing correlation between the given variable and the exposure on the bias and variance for the total effect of the exposure on the outcome using unadjusted and adjusted models. We derived closed-form solutions for continuous outcomes using linear regression and empirically present our findings for binary outcomes using logistic regression. RESULTS: For models properly specified, total effect estimates remained unbiased even when there was almost perfect correlation between the exposure and a given intermediate, confounder, or collider. In general, as the correlation increased, the variance of the parameter estimate for the exposure in the adjusted models increased, while in the unadjusted models, the variance increased to a lesser extent or decreased. CONCLUSION: Our findings highlight the importance of considering the causal framework under study when specifying regression models. Strategies that do not take into consideration the causal structure may lead to biased effect estimation for the original question of interest, even under high correlation. PMID- 27676262 TI - Diffusion Coefficient and Relaxation Time of Aliphatic Spin Probes in a Unique Triglyceride Membrane. AB - The molecular dynamics of aliphatic spin probes in a unique triglyceride membrane were investigated by continuous wave electron paramagnetic resonance (CW EPR) and saturation recovery spectroscopic methods. Rotational diffusion coefficients (R? and R?) obtained by a slow-motional EPR spectral simulation for 7-doxylstearic acid (7-DSA), 12-doxylstearic acid (12-DSA), and 16-doxylstearic acid (16-DSA) in the membrane at various temperatures were obtained. The activation energies calculated using R? values for 7-, 12-, and 16-DSA in the membrane were 19 +/- 0.9, 24 +/- 1.2, and 37 +/- 1.8 kJ/mol, respectively. The higher activation energy implies that the perpendicular motion of 16-DSA is more sensitive to temperature. As the nitroxide group of the spin probe was moved further down the stearic chain, electron spin-lattice relaxation times (T1e) became shorter. The shorter T1e indicates more flexibility around the probe moiety. Also, T1e for the DSAs became shorter when the temperature increased. The values of T1e obtained were consistent with perpendicular diffusion coefficients. In addition, no significant difference in T1e between the H2O and the D2O solutions was observed for the different DSAs. Therefore, it is concluded that steric effects and the local rotational mobility of the nitroxide moiety influence the T1e's obtained. PMID- 27676261 TI - Robotic Assisted Cannulation of Occluded Retinal Veins. AB - PURPOSE: To develop a methodology for cannulating porcine retinal venules using a robotic assistive arm after inducing a retinal vein occlusion using the photosensitizer rose bengal. METHODOLOGY: Retinal vein occlusions proximal to the first vascular branch point were induced following intravenous injection of rose bengal by exposure to 532nm laser light delivered by slit-lamp or endolaser probe. Retinal veins were cannulated by positioning a glass catheter tip using a robotically controlled micromanipulator above venules with an outer diameter of 80MUm or more and performing a preset piercing maneuver, controlled robotically. The ability of a balanced salt (BSS) solution to remove an occlusion by repeat distention of the retinal vein was also assessed. RESULTS: Cannulation using the preset piercing program was successful in 9 of 9 eyes. Piercing using the micromanipulator under manual control was successful in only 24 of 52 attempts, with several attempts leading to double piercing. The best location for cannulation was directly proximal to the occlusion. Infusion of BSS did not result in the resolution of the occlusion. CONCLUSION: Cannulation of venules using a robotic microassistive arm can be achieved with consistency, provided the piercing is robotically driven. The model appears robust enough to allow testing of therapeutic strategies aimed at eliminating a retinal vein thrombus and its evolution over time. PMID- 27676263 TI - Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function. AB - Outgrowth endothelial cells (OECs) are a subpopulation of endothelial progenitor cells (EPCs) that have the capacity for proliferation and the ability to promote angiogenesis. In this study, we identified Nectin-2 as a surface protein of OECs through unbiased quantitative proteomics analysis. Using immunocytochemistry and flow cytometry, we confirmed that Nectin-2 is highly expressed on OECs. Nectin-2 (CD112) expression was limited or lower on mononuclear cells (MNCs) and mature tube-forming endothelial cells (ECs). Blocking Nectin-2 with a neutralizing monoclonal antibody significantly increased the trans-well migration and tube forming capacity of OECs. Similarly, Nectin-2 knockdown resulted in enhanced tube formation, cell migration and proliferation with p-Erk activation. Moreover, Nectin-2 deficiency resulted in compensatory increase of other Nectin family genes including Nectin-3 and Necl-4 which promote VEGFR signaling. These results indicate that Nectin-2 is a surface marker and an important regulator of OECs, with significant implications for the isolation of OECs and blocking Nectin-2 on OECs by an antibody for angiogenic applications. PMID- 27676264 TI - Ternary FexCo1-xP Nanowire Array as a Robust Hydrogen Evolution Reaction Electrocatalyst with Pt-like Activity: Experimental and Theoretical Insight. AB - Replacement of precious Pt with earth-abundant electrocatalysts for the hydrogen evolution reaction (HER) holds great promise for clean energy devices, but the development of low-cost and durable HER catalysts with Pt-like activity is still a huge challenge. In this communication, we report on the development of self standing ternary FexCo1-xP nanowire array on carbon cloth (FexCo1-xP/CC) as a Pt free HER catalyst with activities being strongly related to Fe substitution ratio. Electrochemical tests show that Fe0.5Co0.5P/CC not only possesses Pt-like activity with the need of overpotential of only 37 mV to drive 10 mA cm-2, outperforming all non-noble-metal HER catalysts reported to date, but demonstrates superior long-term durability in 0.5 M H2SO4. Density functional theory calculations further reveal that Fe substitution of Co in CoP leads to more optimal free energy of hydrogen adsorption to the catalyst surface. This study offers us a promising flexible monolithic catalyst for practical applications. PMID- 27676265 TI - Enzymatic Reductive Dehalogenation Controls the Biosynthesis of Marine Bacterial Pyrroles. AB - Enzymes capable of performing dehalogenating reactions have attracted tremendous contemporary attention due to their potential application in the bioremediation of anthropogenic polyhalogenated persistent organic pollutants. Nature, in particular the marine environment, is also a prolific source of polyhalogenated organic natural products. The study of the biosynthesis of these natural products has furnished a diverse array of halogenation biocatalysts, but thus far no examples of dehalogenating enzymes have been reported from a secondary metabolic pathway. Here we show that the penultimate step in the biosynthesis of the highly brominated marine bacterial product pentabromopseudilin is catalyzed by an unusual debrominase Bmp8 that utilizes a redox thiol mechanism to remove the C-2 bromine atom of 2,3,4,5-tetrabromopyrrole to facilitate oxidative coupling to 2,4 dibromophenol. To the best of our knowledge, Bmp8 is first example of a dehalogenating enzyme from the established genetic and biochemical context of a natural product biosynthetic pathway. PMID- 27676266 TI - Inhibitory Effect of beta-Elemene on Human Airway Granulation Tissue in vivo and in vitro. AB - BACKGROUND: Recurrent airway granulation hyperplasia and scar formation make airway stenosis a clinical challenge. Therefore, a new approach for the treatment of airway stenosis is necessary. OBJECTIVE: To explore the inhibitory effect of beta-elemene on the proliferation of fibroblasts and airway granulation. METHODS: In vivo: (1) study of the effect of local beta-elemene injection by bronchoscopy. (2) During bronchoscopy, granulation tissues both before and after treatment were obtained. HE staining was performed and the result compared. In vitro: (1) human airway primary fibroblasts were purified and characterized. (2) Fibroblasts were treated with beta-elemene and normal saline (NS) and then examined by optical and electron microscopy. (3) Fibroblasts treated with beta-elemene or NS were assessed for viability by tetrazolium salt assay. (4) Apoptotic rates were determined by flow cytometry. RESULTS: In vivo: (1) after local injection of beta elemene, airway granulation tissue was reduced. (2) Granulation tissue was found to have less edema, and fibroblasts turned into mature fiber cells. In vitro: (1) human airway primary fibroblasts were successfully purified and cultured. (2) Compared with the control group, fibroblasts of the experimental group became clumped, the plasma granules were increased, and some fibroblasts lost their nucleus and organelles. (3) Compared with the control group, reduction of cell viability was detected with increased concentrations of beta-elemene. (4) With increased concentrations of beta-elemene, apoptotic rates of the fibroblasts were raised compared with the control group. CONCLUSIONS: beta-Elemene may induce apoptosis and necrosis of airway primary fibroblasts and inhibit the proliferation of fibroblasts and airway granulation. The results provide a new approach for the treatment of airway stenosis. PMID- 27676267 TI - Synthesis and Reactivity of Electronically Unsaturated Dirhenium Carbonyl Compounds Containing Bridging Gold-Carbene Groups. AB - The electronically unsaturated compounds Re2(CO)8[MU-Au(NHC)](MU-Ph), 1, and Re2(CO)8[MU-Au(NHC)]2, 2, were obtained from the reaction of Re2(CO)8[MU-eta2 C(H)?C(H)Bun](MU-H) with MeAu(NHC), NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol 2-ylidene. Compound 1 was converted to the new compound Re2(CO)8[MU-Au(NHC)](MU H), 3, by reaction with H2. Addition of CO to 3 yielded the new compound Re2(CO)9[Au(NHC)](MU-H), 4, which contains a terminally coordinated Au(NHC) group on one of the rhenium atoms, and the hydrido ligand was shifted to bridge the Re Au bond. The mechanism of the formation of 4 was established by DFT computational analyses. Compound 3 also reacted with C2H2 by an addition with insertion into the Re-H bonds to yield the compound Re2(CO)8[MU-Au(NHC)](MU-C2H3), 5, which contains a sigma-pi coordinated, bridging C2H3 ligand. The stereochemistry of the insertion was found to proceed preferentially with a cis- (syn-) stereochemistry. Compound 1 reacted with HCl to yield Re2(CO)8[MU-Ph](MU-H), 6, and ClAu(NHC) by selective removal of the bridging Au(NHC) group. All new compounds were characterized by single-crystal X-ray diffraction analyses. PMID- 27676268 TI - Surgical Treatment of Facial Basal Cell Carcinoma: Patient-Based Assessment of Clinical Outcome in a Prospective Cohort Study. AB - BACKGROUND: There are limited data on the esthetic, functional, and morphological outcomes of surgical treatment of facial basal cell carcinoma (BCC). OBJECTIVE: The aim of our study was to assess the determinants of the evaluation of both the patients and the investigator of the esthetic, functional, and morphological impact of the surgical treatment of facial BCC. METHODS: A prospective observational study evaluated 111 patients treated surgically for facial BCCs (n = 135 BCCs), using the Patient and Observer Scar Assessment Scale (POSAS), a validated and reliable scale designed for the evaluation of all types of scars by professionals and patients. RESULTS: Scar assessment rated by the patients was very good. Skin aging was associated with a better surgical outcome as evaluated by POSAS (OR = 0.30, 95% CI: 0.09-0.98; p = 0.04). Conversely, histologically infiltrative or sclerosing BCC (OR = 2.33, 95% CI: 0.95-5.71; p = 0.06) was independently associated with poorer POSAS. In terms of the investigator's evaluation, aging signs (protective factor: OR = 0.17, 95% CI: 0.04-0.73; p = 0.01), location on the H-zone of the face (risk factor: OR = 2.95, 95% CI: 1.07 8.15; p = 0.03), and histologically infiltrative or sclerosing BCC (risk factor: OR = 2.89, 95% CI: 1.01-8.29; p = 0.04) were independently associated with POSAS. CONCLUSION: Esthetic, functional, and morphological outcomes of facial BCC surgery provide high patient satisfaction overall. Taking wider margins requires specific measures to improve the surgical outcome. PMID- 27676269 TI - Nonhydrolyzable C-disaccharides, a new class of DC-SIGN ligands. AB - The discovery of effective ligands for DC-SIGN receptor is one of the most challenging concepts of antiviral drug design due to the importance of this C type lectin in infection processes. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides but glycosidic linkages are accessible to both chemical and enzymatic degradations. To avoid this problem, the synthesis of stable glycoside mimetics has attracted increasing attention. In this work we establish for the first time mono- and divalent C-glycosides based on d-manno and l-fuco configurations as prospective DC-SIGN ligands. In particular, the l-fucose glycomimetics were more active than the respective d-mannose ones. The highest affinity was assessed for simple 1,4-bis(alpha-l-fucopyranosyl)butane (SPR: IC50 0.43 mM) that displayed about twice higher activity than natural ligand Lex. Our results make C-glycosides attractive candidates for multivalent presentations. PMID- 27676270 TI - The Effects of Tai Chi on Sleep Quality in Chinese American Patients With Major Depressive Disorder: A Pilot Study. AB - OBJECTIVE: This pilot study evaluated the effects of Tai Chi training on sleep quality (primary outcomes), and depression and social functioning levels (secondary outcomes) among patients with depression. PARTICIPANTS: Sixteen depressed Chinese patients. METHODS: Participants received 1-hr Tai Chi training sessions 2 times per week for 10 weeks. Patients' subjective sleep quality ratings, objective sleep quality measurements, and depression and social functioning levels were measured before, during, and after the intervention. RESULTS: Sleep quality and depression outcomes improved significantly. Patients reported improved Pittsburgh Sleep Quality Index (PSQI) scores (9.6 +/- 3.3 to 6.6 +/- 5.2, p = 0.016), and cardiopulmonary coupling (CPC) analysis of electrocardiogram (ECG) showed decreased stable sleep onset latency (75.7 +/- 100.6 to 20.9 +/- 18.0, p = 0.014), increased stable sleep percentages (31.5 +/- 18.7 to 46.3 +/- 16.9, p = 0.016), and decreased unstable sleep percentages (45.3 +/- 20.1 to 30.6 +/- 16.5, p = 0.003). Patients also reported decreased Hamilton Rating Scale for Depression (HAM-D-17; 20.1 +/- 3.7 to 7.8 +/- 5.9, p < 0.001) and Beck Depression Inventory (BDI) scores (22.3 +/- 9.1 to 11.1 +/- 10.6, p = 0.006). Significant correlations were found between the changes in subjective sleep assessments DeltaPSQI and DeltaHAM-D-17 (r = 0.6, p = 0.014), and DeltaPSQI and DeltaBDI (r = 0.62, p = 0.010). Correlations between changes in objective sleep measurements and changes in depression symptoms were low and not significant. CONCLUSIONS: Tai Chi training improved sleep quality and mood symptoms among depressed patients. PMID- 27676271 TI - Perceptions of Group-Based Walks and Strategies to Inform the Development of an Intervention in Retirement Villages: Perspectives of Residents and Village Managers. AB - The aim of the current study was to explore perceptions of group-based walking and gather suggestions to inform the development of a group-based walking intervention among older adults in retirement villages. Twenty-four physically inactive residents (16 female, 8 male; age range: 69-88) and four managers from four retirement villages were interviewed. Inductive thematic analysis revealed six broad themes: lack of motivation, values versus constraints, fears and confidence, need for structure, creating a sense of belonging, and the physical environment as a double-edged sword. Proposed intervention strategies included using trained walk leaders, using small groups, planning for flexibility, setting attainable goals, creating a routine, creating opportunities for sharing experiences, and planning a variety of walks. Group-based walking programs may be used to promote physical activity but careful planning of such programs is needed to make them appealing and feasible to a diverse group of residents. PMID- 27676272 TI - Early Predictors of Acute Kidney Injury: A Narrative Review. AB - Accompanied with the broad application of interventional therapy, the incidence of acute kidney injury (AKI) has been recently increasing in clinical renal medicine. The pathogenesis of AKI is diverse and complex. In the context of the requirements for the diagnosis and treatment of a renal disorder, a large number of studies have explored biological markers and their usefulness to the early diagnosis and treatment of AKI, including glomerular injury, renal tubular injury, and others. These biomarkers provide an important basis for early monitoring of AKI, but are still not quite sufficient. More ideal biomarkers are needed to be identified. Therefore, future studies are necessary to explore more effective biomarkers for AKI clinical practice, which would play an important role in the early diagnosis and intervention treatment of AKI. This review summarizes the important biomarkers identified by previous studies and aims to highlight the advancements that might provide new methods for early clinical diagnosis and effective therapeutic options, along with prediction of response to treatment for AKI. PMID- 27676273 TI - Influence of a Personal Trainer on Self-selected Loading During Resistance Exercise. AB - Dias, MRC, Simao, RF, Saavedra, FJF, and Ratamess, NA. Influence of a personal trainer on self-selected loading during resistance exercise. J Strength Cond Res 31(7): 1925-1930, 2017-The purpose of this study was to compare differences in muscle strength and self-selected resistance training intensities between trained subjects who trained under the supervision of a personal trainer (PT) and those who trained without supervision (WoPT). Twenty-one trained subjects, men (n = 12) and women (n = 9), completed 3 sessions (separated by 48 hours) in the following sequence: first session, self-selected intensity assessment consisting of performance of 3 sets of 10 repetitions for the leg press (LP), bench press (BP), leg extension (LE), and arm curl (AC) exercises with self-selected load; second session, a 1 repetition maximum (1RM) test to determine subjects' maximal strength in the 4 exercises; and third session, a 10RM test to determine the maximum load completed for 10 repetitions for each exercise. Self-selected training loads were significantly higher in PT compared with WoPT for the LP (by 15.6%), BP (by 26.6%), LE (by 12.1%), and AC (by 22.2%) exercises. Self-selected training loads expressed relative to 1RM and 10RM data were significantly higher in PT (49-59.5% of 1RM; 62.7-77.3% of 10RM) than WoPT (41-58.7% of 1RM; 58.7 76.2% of 10RM) with largest difference observed in the lower-body exercises. Ratings of perceived exertion values were significantly higher in PT compared with WoPT. The results of the present study indicated that supervised resistance training with a personal trainer was advantageous in trained subjects although self-selected loading was still considerably lower than 1RM and 10RM percentage values. PMID- 27676274 TI - Differential Effects of Continuous Versus Discontinuous Aerobic Training on Blood Pressure and Hemodynamics. AB - Landram, MJ, Utter, AC, Baldari, C, Guidetti, L, McAnulty, SR, and Collier, SR. Differential effects of continuous versus discontinuous aerobic training on blood pressure and hemodynamics. J Strength Cond Res 32(1): 97-104, 2018-The purpose of this study was to compare the hemodynamic, arterial stiffness, and blood flow changes after 4 weeks of either continuous or discontinuous aerobic exercise in adults. Forty-seven subjects between the ages of 18 and 57 were recruited for 1 month of either continuous aerobic treadmill work for 30 minutes at 70% max heart rate or 3 bouts of 10 minutes of exercise at 70% of max heart rate with two 10 minutes break periods in between, totaling 30 minutes of aerobic work. After exercise, both continuous (CON) and discontinuous (DIS) groups demonstrated a significant improvement in maximal oxygen uptake (V[Combining Dot Above]O2max, CON 35.39 +/- 1.99 to 38.19 +/- 2.03; DIS 36.18 +/- 1.82 to 39.33 +/- 1.75), heart rate maximum (CON 183.5 +/- 3.11 to 187.17 +/- 3.06; DIS 179.06 +/- 2.75 to 182 +/- 2.61), decreases in systolic blood pressure (CON 119 +/- 1.82 to 115.11 +/- 1.50; DIS 117.44 +/- 1.90 to 112.67 +/- 1.66), diastolic blood pressure (CON 72.56 +/- 1.65 to 70.56 +/- 1.06; DIS 71.56 +/- 1.59 to 69.56 +/- 1.43), augmentation index (CON 17.17 +/- 2.17 to 14.9 +/- 1.92; DIS 19.71 +/- 2.66 to 13.91 +/- 2.46), central pulse wave velocity (CON 8.29 +/- 0.32 to 6.92 +/- 0.21; DIS 7.85 +/- 0.30 to 6.83 +/- 0.29), peripheral pulse wave velocity (CON 9.49 +/- 0.35 to 7.72 +/- 0.38; DIS 9.11 +/- 0.37 to 7.58 +/- 0.47), and significant increases in average forearm blood flow (CON 4.06 +/- 0.12 to 4.34 +/- 0.136; DIS 4.26 +/- 0.18 to 4.53 +/- 0.15), peak forearm blood flow (FBF) after reactive hyperemia (CON 28.45 +/- 0.094 to 29.96 +/- 0.45; DIS 29.29 +/- 0.46 to 30.6 +/- 0.38), area under the curve (AUC) of FBF (CON 28.65 +/- 1.77 to 30.4 +/- 1.08; DIS 30.52 +/- 1.9 to 31.67 +/- 1.44), and AUC peak FBF after reactive hyperemia (CON 222.3 +/- 5.68 to 231.95 +/- 4.42; DIS 230.81 +/- 6.91 to 237.19 +/- 5.39). These data suggest that for healthy people either 4 weeks of continuous or discontinuous aerobic training is effective in improving measures of fitness and vascular health. PMID- 27676275 TI - Hormonal (Cortical-Gonadotropic Axis) and Physical Changes With Two Years Intense Exercise Training in Elite Young Soccer Players. AB - Hammami, MA, Ben Abderrahman, A, Hackney, AC, Kebsi, W, Owen, AL, Nebigh, A, Racil, G, Tabka, Z, and Zouhal, H. Hormonal (cortical-gonadotropic axis) and physical changes with two years intense exercise training in elite young soccer players. J Strength Cond Res 31(9): 2388-2397, 2017-The aim of this study was to investigate the effects of 2 soccer-training seasons on physical fitness and hormone concentrations in elite youth soccer players. Twenty male elite soccer players (SP, age 14.5 +/- 0.4 years) and 20 male control subjects (CS, age 14.3 +/- 0.3 years) participated in the study. Anthropometric measurements, aerobic (Yo-Yo Intermittent Recovery Test Level 1 [YYIRT1]) and anaerobic soccer relevant performances (jump and sprint tests), blood testosterone (T), cortisol (C), sex hormone binding globulin (SHBG), and T/C ratio were assessed 5 times (from T0 to T4) during 2 competitive seasons. Significant differences from basal values (Delta) of T, SHBG, and C between SP and CS were observed (p < 0.01). Additionally, T and T/C ratio changes were positively correlated with physical performance (p <= 0.05). In conclusion, as expected, higher T concentration and greater power performance were observed in the soccer players group compared with controls. Our findings also show that the T concentrations and power performance outcomes co-vary positively over the 2 soccer seasons in soccer players. PMID- 27676276 TI - Modified mRNA for BMP-2 in Combination with Biomaterials Serves as a Transcript Activated Matrix for Effectively Inducing Osteogenic Pathways in Stem Cells. AB - Bone regeneration using stem cells and growth factors has disadvantages while needing to use supraphysiological growth factors concentrations. Gene therapy has been proposed as alternative, but also has limitation. Messenger RNA (mRNA)-based transcript therapy is a novel approach that may solve plasmid DNA-based gene therapy limitations. Although much more efficient in delivering genes into the cell, mRNA is unfortunately unstable and immunogenic. However, recent reports indicated that chemical modifications of the mRNA molecule can improve stability and toxicity. In this study, we have combined biomaterials and chemically modified mRNA (cmRNA) encoding Metridia luciferase, eGFP, and bone morphogenetic protein (BMP)-2 to develop transcript-activated matrices (TAMs) for gene transfer to stem cells. BMP-2 cmRNA was produced to evaluate its feasibility in stimulating osteogenic differentiation. Fibrin gel and micro-macro biphasic calcium phosphate (MBCP) granules were used as biomaterials. A sustained release of hBMP-2 cmRNA from both biomaterials was observed during 7 days. This occurred significantly faster from the MBCP granules compared to fibrin gels (92% from MBCP and 43% from fibrin after 7 days). Stem cells cultured in hBMP-2 cmRNA/fibrin or on hBMP-2 cmRNA/MBCP were transfected and able to secrete significant amounts of hBMP-2. Furthermore, transfected cells expressed osteogenic markers in vitro. Interestingly, although both TAMs promoted gene expression at the same level, hBMP-2 cmRNA/MBCP granules induced significantly higher collagen I and osteocalcin gene expression. This matrix also induced more mineral deposition. Overall, our results demonstrated the feasibility of developing efficient TAMs for bone regeneration by combining biomaterials and cmRNAs. MBCP synergistically enhances the hBMP-2 cmRNA-induced osteogenic pathway. PMID- 27676277 TI - Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. AB - AIM: Evaluate the potential of selected SNPs as predictors of methotrexate (MTX) therapeutic outcome. PATIENTS & METHODS: In total, 35 SNPs in 14 genes involved in MTX intracellular pathways and Phase II reactions were genotyped in 233 rheumatoid arthritis (RA) patients treated with MTX. Binary logistic regressions were performed by genotype/haplotype-based approaches. Non-Response- and Toxicity Genetic Risk Indexes (Non-RespGRI and ToxGRI) were created. RESULTS: MTX nonresponse was associated to eight genotypes and three haplotypes: MTHFR rs1801131 AA and rs1801133 TT; MS rs1805087 AA; MTRR rs1801394 A carriers; ATIC rs2372536 C carriers, rs4673993 T carriers, rs7563206 T carriers and rs12995526 T carriers; CC for GGH rs3758149 and rs12681874; CGTTT for ATIC combination 1; and CTTTC for ATIC combination 2. From overall Non-RespGRI patients with indexes 6-8 had more than sixfold increased risk for MTX nonresponse than those patients with indexes 0-5. MTX-related toxicity was associated to five genotypes and two haplotypes: ATIC rs2372536 G carriers, rs3821353 T carriers, rs7563206 CC and rs12995526 CC; ADORA2A rs2267076 T; CTTCC for ATIC combination 1; and TC for ADORA2A rs2267076 and rs2298383. From overall ToxGRI, patients with indexes 3-4 had more than sevenfold increased risk for MTX-related toxicity than those patients with indexes 1-2. CONCLUSION: Genotyping may be helpful to identify which RA patients will not benefit from MTX treatment and, consequently, important to personalized medicine in RA. Nevertheless, further studies are required to validate these findings. PMID- 27676279 TI - Current management of low-grade gliomas. AB - PURPOSE OF REVIEW: The management of patients suffering from low-grade gliomas (LGGs) remains a challenge in absence of a definite curative therapy. The median survival is highly variable, from 2 years (high-risk disease) to over 15 years (low risk). The aim of this review is to provide a practical step-by-step evaluation of the available treatment options for patients with LGGs. RECENT FINDINGS: Next to clinical prognostic markers, both the isocitrate dehydrogenase (IDH) mutation status and the status of 1p/19q codeletion are key prognostic factors for the optimal management of patients with LGG. Two recent randomized phase III clinical trials were performed in LGGs. They first compared the efficacy of radiation versus temozolomide (TMZ) chemotherapy in high-risk LGGs. The second trial compared radiation versus radiation combined with procarbazine, lomustine and vincristine chemotherapy. SUMMARY: Regarding molecular prognostic factors, IDH wild-type LGGs have the worst prognosis, independent of therapy, whereas patients with mutated IDH, codeleted 1p/19q LGGs fared best regarding progression-free survival (PFS). In high-risk LGGs, PFS is similar regardless of whether patients have been treated with radiation or TMZ. In the second trial, patients who were treated with combination radiation and chemotherapy showed significant longer overall survival. PMID- 27676278 TI - The confused oncologic patient: a rational clinical approach. AB - PURPOSE OF REVIEW: The purpose of this review is to provide a practical clinical approach to confusion in the patient with cancer. Confusion in the cancer population has a broader differential diagnosis than in the general medical population. The clinician must consider the usual differential diagnoses as well as causes unique to the cancer patient including direct complications from the cancer and indirect complications related to cancer treatment. RECENT FINDINGS: In the recent age of precision medicine, the oncologist now utilizes the genomic profile of both the patient and the tumor to provide advanced biologic therapies including targeted anticancer drugs, antiangiogenic agents, and immunotherapy. Such advances carry with them an emerging pattern of neurotoxicity which, although less well described in the literature, is now an important consideration to the clinical approach to confusion in cancer patients. SUMMARY: Confusion is the most common neurologic complication in cancer and is associated with significant morbidity, mortality, and prolonged hospital stays resulting in increased healthcare costs. Early recognition and treatment of delirium is essential to improve clinical outcomes. PMID- 27676280 TI - Evaluation of Silver Ion-Releasing Scaffolds in a 3D Coculture System of MRSA and Human Adipose-Derived Stem Cells for Their Potential Use in Treatment or Prevention of Osteomyelitis. AB - Bone infection, also called osteomyelitis, can result when bacteria invade a bone. Treatment of osteomyelitis usually requires surgical debridement and prolonged antimicrobial therapy. The rising incidence of infection with multidrug resistant bacteria, in particular methicillin-resistant staphylococcus aureus (MRSA), however, limits the antimicrobial treatment options available. Silver is well known for its antimicrobial properties and is highly toxic to a wide range of microorganisms. We previously reported our development of biocompatible, biodegradable, nanofibrous scaffolds that released silver ions in a controlled manner. The objective of this study was to determine the efficacy of these scaffolds in treating or preventing osteomyelitis. To achieve this objective, antimicrobial efficacy was determined using a 3D coculture system of human adipose-derived stem cells (hASC) and MRSA. Human ASC were seeded on the scaffolds and induced to undergo osteogenic differentiation in both the absence and presence of MRSA. Our results indicated that the silver ion-releasing scaffolds not only inhibited biofilm formation, but also supported osteogenesis of hASC. Our findings suggest that these biocompatible, degradable, silver ion releasing scaffolds can be used at an infection site to treat osteomyelitis and/or to coat bone implants as a preventative measure against infection postsurgery. PMID- 27676281 TI - Narrative Review of Statistical Reporting Checklists, Mandatory Statistical Editing, and Rectifying Common Problems in the Reporting of Scientific Articles. AB - Considerable attention has been drawn to poor reproducibility in the biomedical literature. One explanation is inadequate reporting of statistical methods by authors and inadequate assessment of statistical reporting and methods during peer review. In this narrative review, we examine scientific studies of several well-publicized efforts to improve statistical reporting. We also review several retrospective assessments of the impact of these efforts. These studies show that instructions to authors and statistical checklists are not sufficient; no findings suggested that either improves the quality of statistical methods and reporting. Second, even basic statistics, such as power analyses, are frequently missing or incorrectly performed. Third, statistical review is needed for all papers that involve data analysis. A consistent finding in the studies was that nonstatistical reviewers (eg, "scientific reviewers") and journal editors generally poorly assess statistical quality. We finish by discussing our experience with statistical review at Anesthesia & Analgesia from 2006 to 2016. PMID- 27676282 TI - Bradycardia in Zebrafish Heart Failure: A True Physiological Response or Anesthetic-Induced Red Herring? PMID- 27676283 TI - Spinal melanocytoma with leptomeningeal spread and long survival following surgery and chemotherapy. PMID- 27676284 TI - Successful use of bevacizumab in an adult primary diffuse leptomeningeal glioneuronal tumor. PMID- 27676285 TI - Factors affecting unmet need for contraception among currently married fecund young women in Bangladesh. AB - OBJECTIVES: The aim of our study was to explore the factors associated with unmet need for contraception among currently married fecund women under age 25, in Bangladesh. METHODS: This study utilised a cross-sectional data (n = 4982) extracted from the Bangladesh Demographic and Health Survey (BDHS) 2011. Multinomial logistic regression was used to identify the determinants of unmet need for contraception among currently married fecund young women. RESULTS: The unmet need for contraception was 17% and contraceptive prevalence was 54% in this young group. Total demand for contraception was 71% and the proportion of demand satisfied was 77%. The results suggest that region, place of residence, religion, husband's desire for children, visits of FP workers, decision-making power on child health care, reading about FP in newspaper/magazine and number of births in three years preceding the survey were significant predictors of unmet need for contraception. CONCLUSIONS: The BDHS of 2011 found that unmet need for contraception among currently married, fecund women under 25 years old is higher than the national level, and hence different or more intensive programme initiatives are required for them than for older women. The present study identifies important predictors of unmet need for contraception among fecund married Bangladeshi women under age 25. PMID- 27676286 TI - Blood pressure response to medical treatment in the emergency department - a retrospective cohort study. AB - OBJECTIVES: It is unclear whether blood pressure (BP) without target organ damage should be decreased in patients in the emergency department (ED). It is also uncertain whether any certain class of medications has an advantage over the other in this setting. This study addressed both these questions. METHODS: In this retrospective cohort study, all patients attending a tertiary care ED with elevated BP were evaluated. All patients with target organ damage as well as those with significant active co-morbidities, such as myocardial ischemia, were excluded. Baseline characteristics and response of BP to therapy were compared between those treated and untreated in the ED. In addition, BP response to therapy was compared between different classes of antihypertensive medications. RESULTS: Overall, 438 patients were included in the final analysis (62% female), of which 275 (63%) were treated in the ED. Antihypertensive medications were more commonly prescribed in the ED for those with higher systolic and diastolic BP, but other baseline characteristics were similar between the two groups. Only systolic BP significantly decreased in those treated with antihypertensive medications compared with those untreated. The most commonly used classes were angiotensin converting enzyme inhibitors (ACEis) and calcium channel blockers (CCBs). Use of either of these drug classes was not associated with a significant decrease in either systolic or diastolic BP compared with the use of other drug classes. CONCLUSIONS: Antihypertensive drug therapy is more commonly prescribed in the ED in individuals with both elevated systolic and diastolic BP, but leads to a significant decrease only in systolic BP. Use of either ACEis or CCBs is not associated with a significant decrease in either systolic or diastolic BP compared with other drug classes. PMID- 27676288 TI - A simple, rapid method for evaluation of transfection efficiency based on fluorescent dye. AB - Enhanced transfection efficiency of transient gene expression (TGE) and electroporation is a useful approach for improvement of recombinant therapeutic proteins in mammalian cells. A novel method is described here in which CHO cells expressing recombinant FVII (rFVII) were labeled with fluorescent dye and analyzed by confocal microscopy. Cells with or without rFVII encoding gene were detectable by flow cytometry. Thus, we were able to distinguish positive cells (with rFVII encoding gene) and quantify their percentages. We evaluated the effects of varying electroporation conditions (voltage, number of repetitions, plasmid amount, carrier DNA) in order to optimize transfection efficiency. The highest transfection efficiency achieved was ~86%. The method described here allows rapid evaluation of transfection efficiency without co-expression of reporter genes. In combination with appropriate antibodies, the method can be extended to evaluation of transfection efficiency in cells expressing other recombinant proteins. PMID- 27676287 TI - Characteristics of Clusters of Salmonella and Escherichia coli O157 Detected by Pulsed-Field Gel Electrophoresis that Predict Identification of Outbreaks. AB - INTRODUCTION: Molecular subtyping of pathogens is critical for foodborne disease outbreak detection and investigation. Many clusters initially identified by pulsed-field gel electrophoresis (PFGE) are not confirmed as point-source outbreaks. We evaluated characteristics of clusters that can help prioritize investigations to maximize effective use of limited resources. MATERIALS AND METHODS: A multiagency collaboration (FoodNet) collected data on Salmonella and Escherichia coli O157 clusters for 3 years. Cluster size, timing, extent, and nature of epidemiologic investigations were analyzed to determine associations with whether the cluster was identified as a confirmed outbreak. RESULTS: During the 3-year study period, 948 PFGE clusters were identified; 849 (90%) were Salmonella and 99 (10%) were E. coli O157. Of those, 192 (20%) were ultimately identified as outbreaks (154 [18%] of Salmonella and 38 [38%] of E. coli O157 clusters). Successful investigation was significantly associated with larger cluster size, more rapid submission of isolates (e.g., for Salmonella, 6 days for outbreaks vs. 8 days for nonoutbreaks) and PFGE result reporting to investigators (16 days vs. 29 days, respectively), and performance of analytic studies (completed in 33% of Salmonella outbreaks vs. 1% of nonoutbreaks) and environmental investigations (40% and 1%, respectively). Intervals between first and second cases in a cluster did not differ significantly between outbreaks and nonoutbreaks. CONCLUSIONS: Molecular subtyping of pathogens is a rapidly advancing technology, and successfully identifying outbreaks will vary by pathogen and methods used. Understanding criteria for successfully investigating outbreaks is critical for efficiently using limited resources. PMID- 27676290 TI - Mediators of the relationship between social activities and cognitive function among older Irish adults: results from the Irish longitudinal study on ageing. AB - OBJECTIVE: Evidence points to an association between social and leisure activity (SLA) engagement and cognitive outcomes, but the mechanisms underlying this link remain unknown. We aimed to investigate three potential mechanisms: Vascular function, Perceived Stress, and Cognitive Reserve. METHODS: With data from 8163 adults aged over 50 in the Irish Longitudinal Study of Ageing, we used a structural equation model to evaluate Vascular Function and Perceived Stress as potential mediators, and Cognitive Reserve as a potential antecedent in the relationship between SLA at baseline (2009), and cognitive outcomes collected at a two-year follow-up point (2011). RESULTS: Cognitive Reserve was strongly associated both with cognitive outcomes (beta = 0.306; p < 0.001) and with SLA (beta = 0.694; p < 0.001). Perceived stress (beta = 0.018) acted as a significant mediator in the relationships between SLA and cognitive outcomes (p < 0.001), although Vascular Function did not (beta = 0.000). CONCLUSION: These results indicate that SLA may protect cognitive function partly because of its association with cognitive reserve, and partly through its impact on perceived stress. Results have policy implications for those interested in facilitating SLA to protect cognitive outcomes among older adults. PMID- 27676291 TI - Mapping EORTC-QLQ-C30 to EQ-5D-3L in patients with colorectal cancer. AB - AIMS: The primary aim of this study was to perform a mapping of the EORTC-QLQ-C30 scores to EQ-5D-3L for the SIRFLOX study; a large dataset of patients with previously untreated liver-only or liver-dominant metastatic colorectal cancer (mCRC). A secondary aim was to compare the predictive validity of existing mappings from EORTC-QLQ-C30 to EQ-5D-3L conducted in other cancers. METHODS AND MATERIALS: Questionnaires (completed within 529 patients) were used in a linear mixed regression to model EQ-5D-3L utility values (scored using the UK tariff) as a function of the five function scores, nine symptom scores, and the global score from the EORTC-QLQ-C30 questionnaire. A Tobit regression was also performed. The mean EQ-5D-3L values for the SIRFLOX trial were calculated and compared with predicted EQ-5D-3L values derived using published mapping algorithms. RESULTS: The linear mixed regression model provided a satisfactory mapping between the EORTC-QLQ-C30 and the EQ-5D-3L, whilst the Tobit model did not perform as well. When utilities from the SIRFLOX data were calculated with previously published mapping studies, three out of five studies performed well (< 10% mean difference). LIMITATIONS: The main limitation of the study was the lack of meaningful observations post-progression (67 paired observations). For this reason, this study was unable to test whether the mapping holds by disease stage. Additionally, although the study adds to the literature of mappings to the EQ-5D 3L, it is not known how results would differ using the EQ-5D-5L. CONCLUSION: This study is the first of its kind in liver-only or liver-dominant mCRC, and mCRC in general. The mapping constructed showed a good fit to the data and provides practitioners with an additional mapping between EORTC-QLQ-C30 to EQ-5D-3L using a large dataset (529 patients, 707 paired observations). The study also confirmed the generalizability of mappings published by Proskorovsky, Kontodimopoulos, and Longworth to liver-only or liver-dominant mCRC. PMID- 27676293 TI - Drosophila SLC5A11 Mediates Hunger by Regulating K+ Channel Activity. PMID- 27676292 TI - RHOB expression controls the activity of serine/threonine protein phosphatase PP2A to modulate mesenchymal phenotype and invasion in non-small cell lung cancers. AB - Metastatic dissemination is the cause of death in the vast majority of cancers, including lung cancers. In order to metastasize, tumor cells must undergo a well known series of changes, however the molecular details of how they manage to overcome the barriers at each stage remain incomplete. One critical step is acquiring the ability to migrate through the extracellular matrix. Loss of expression of the RAS-related small GTPase RHOB is a common feature of lung cancer progression, and we recently reported that this induces an epithelial-to mesenchymal transition (EMT) that is dependent on SLUG overexpression and E Cadherin inhibition and is characterized by 3-dimensional cell shape reorganization and the increased invasiveness of bronchial cells. RHOB loss was found to induce AKT1 activation, which in turn activates RAC1 through its GEF TRIO. Further investigation of this pathway revealed that RHOB interacts with and positively regulates PP2A, one of the major cellular serine-threonine phosphatases, by recruiting its regulatory subunit B55. Here we discuss the role of this newly discovered RHOB/PP2A/AKT1/RAC1 pathway in relation to mesenchymal migration and invasion in lung cancer. PMID- 27676289 TI - State of the science on prevention of elder abuse and lessons learned from child abuse and domestic violence prevention: Toward a conceptual framework for research. AB - The goal of this review is to discuss the state of the science in elder abuse prevention. Findings from evidence-based programs to reduce elder abuse are discussed, drawing from findings and insights from evidence-based programs for child maltreatment and domestic/intimate partner violence. A conceptual measurement model for the study of elder abuse is presented and linked to possible measures of risk factors and outcomes. Advances in neuroscience in child maltreatment and novel measurement strategies for outcome assessment are presented. PMID- 27676294 TI - Increased Glucose Transport into Neurons Rescues Abeta Toxicity in Drosophila. PMID- 27676295 TI - Bio-logging. AB - Fehlmann and King introduce bio-logging techniques to track free-living animals. PMID- 27676296 TI - Gut microbiota signatures of longevity. AB - An aging global population poses substantial challenges to society [1]. Centenarians are a model for healthy aging because they have reached the extreme limit of life by escaping, surviving, or delaying chronic diseases [2]. The genetics of centenarians have been extensively examined [3], but less is known about their gut microbiotas. Recently, Biagi et al.[4] characterized the gut microbiota in Italian centenarians and semi-supercentenarians. Here, we compare the gut microbiota of Chinese long-living people with younger age groups, and with the results from the Italian population [4], to identify gut-microbial signatures of healthy aging. PMID- 27676297 TI - Nrf1 can be processed and activated in a proteasome-independent manner. AB - In response to proteasome inhibition, the transcription factor Nrf1 facilitates de novo synthesis of proteasomes by inducing proteasome subunit (PSM) genes [1,2]. Previously, we showed that activation of the p120 form of Nrf1, a membrane bound protein in the endoplasmic reticulum (ER) with the bulk of its polypeptide in the lumen, involves its retrotranslocation into the cytosol in a manner that depends on the AAA-ATPase p97/VCP [3]. This is followed by proteolytic processing and mobilization of the transcriptionally active p110 form of Nrf1 to the nucleus. A subsequent study suggested that site-specific proteolytic processing of Nrf1 by the proteasome yields an active 75 kDa fragment [4]. We show here that under conditions where all three active sites of the proteasome are completely blocked, p120 Nrf1 can still be proteolytically cleaved to the p110 form, which is translocated to the nucleus to activate transcription of PSM genes. Thus, our results indicate that a proteasome-independent pathway can promote the release of active p110 Nrf1 from the ER membrane. PMID- 27676298 TI - Reply to Vangala et al.: Complete inhibition of the proteasome reduces new proteasome production by causing Nrf1 aggregation. AB - An important adaptation of cells to proteasome inhibition is the induction of new proteasomes via the transcription factor Nrf1 [1,2], which is produced as a precursor bound to the endoplasmic reticulum (ER) through its amino terminus. Nrf1 was reported to require proteolytic processing to enter the nucleus [3]. Increased proteasome production is induced by low concentrations of proteasome inhibitors that reduce proteolysis by <50%. Surprisingly, in earlier studies we found that proteasome induction and Nrf1 processing to its shorter form (which we estimated to be 75 kDa [2]) were suppressed by high concentrations of inhibitors that markedly reduce proteasome activity [4]. This unusual bimodal concentration dependence implied that some proteasome function was necessary for Nrf1 processing. Because we found that Nrf1 processing also required ubiquitin conjugation [2], we previously proposed that Nrf1 processing is catalyzed by partially inhibited proteasomes [2]. However, Vangala et al.[5] present compelling evidence that conversion of the ER-bound Nrf1 to the shorter form, which they describe as 110 kDa, is independent of proteasomes and is not blocked by high concentrations of proteasome inhibitors. Therefore, we investigated the basis for these differing results. Here we report that we and Vangala et al. have studied the same processed form of Nrf1, the actual molecular weight of which appears to be 90-95 kDa. We confirm our earlier finding [2] that high concentrations of proteasome inhibitors suppress proteasome induction and accumulation of processed Nrf1 in soluble lysates. However, we now show that the inhibitors do so not by blocking Nrf1 processing, but instead by causing the processed Nrf1 to aggregate. Therefore, Nrf1 must be cleaved by a non-proteasomal endoprotease that we show requires ubiquitination. Finally, we provide evidence supporting the recent report that Ddi1/Ddi2 is the critical protease [6,7]. PMID- 27676299 TI - Evolutionary Genetics: Reuse, Recycle, Converge. AB - Our understanding of how genetic changes underlie the evolution of traits is growing fast. Two new studies now show that changes in the same genetic loci can drive the evolution of the same trait in multiple Drosophila species. PMID- 27676300 TI - Circadian Rhythms: Understanding the SCN Connectome. AB - A new study utilizes transgenic mice to elucidate the coupling between cells of a neuronal pacemaker that determines circadian period. PMID- 27676301 TI - Plant Pathology: A Life and Death Struggle in Rice Blast Disease. AB - The fungal pathogen Magnaporthe oryzae causes severe disease symptoms and yield losses on rice plants. A new study shows that this fungus elicits disease lesions by co-opting a host protein and reveals how rice plants fight back. PMID- 27676302 TI - Feeding Behavior: Hypocretin/Orexin Neurons Act between Food Seeking and Eating. AB - A report on the rapid change of activity of hypocretin/orexin cells in response to contact rather than digestion of food delivers new insights into the behavioral control of food intake and systemic energy expenditure. PMID- 27676303 TI - Sleep: How Many Switches Does It Take To Turn Off the Lights? AB - Sleeping animals do not move or feed and are less responsive. In Caenorhabditis elegans, a single neuron triggers sleep. A recent study shows that the neuron releases several neuropeptides - each with distinct sleep behavioral effects - to promote the collection of behaviors that is sleep. PMID- 27676304 TI - Venom Evolution: Gene Loss Shapes Phenotypic Adaptation. AB - Snake venoms are variable protein mixtures with a multitude of bioactivities. New work shows, surprisingly, that it is the loss of toxin-encoding genes that strongly influences venom function in rattlesnakes, highlighting how gene loss can underpin adaptive phenotypic change. PMID- 27676305 TI - Genomics: Evolution of the Genetic Code. AB - The genetic code is not quite universal. The rare variations that we know of reveal selective pressures on the code and on the translation machinery. New data suggest the code changes through ambiguous intermediates and that termination is context dependent. PMID- 27676306 TI - Evolution: Ocean Models Reveal Life in Deep Seas. AB - Even though the deep sea represents the largest area in the world, evolution of species from those environments remains largely unstudied. A series of recent papers indicate that combining molecular tools with biophysical models can help us resolve some of these deep mysteries. PMID- 27676307 TI - Developmental Biology: When Less Damage Causes More Harm. AB - Circadian clocks are important timekeepers of physiological processes. A new report shows that silencing the circadian clock specifically in steroid-producing cells of Drosophila disrupts development and causes lethality, and is more detrimental than having no clock at all. PMID- 27676308 TI - Gene Flow and Molecular Innovation in Bacteria. AB - The small molecules produced by environmental bacteria have been mainstays of both chemical and biological research for decades, and some have led to important therapeutic interventions. These small molecules have been shaped by natural selection as they evolved to fulfill changing functional roles in their native environments. This minireview describes some recent systematic studies providing illustrative examples that involve the acquisition and alteration of genetic information for molecular innovation by bacteria in well-defined environments. Two different bacterial genera are featured, Pseudonocardia and Salinispora, and, although the small-molecule repertoires of both have benefited from horizontal gene transfer, Pseudonocardia spp. have relied on plasmid-based tactics while Salinispora spp. have relied on chromosomally integrated genomic islands. PMID- 27676309 TI - Ghrelin accelerates wound healing in combined radiation and wound injury in mice. AB - Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone-releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole-body irradiated (gamma ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS-R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation-induced impaired wound healing. PMID- 27676310 TI - Bony cranial ornamentation linked to rapid evolution of gigantic theropod dinosaurs. AB - Exaggerated cranial structures such as crests and horns, hereafter referred to collectively as ornaments, are pervasive across animal species. These structures perform vital roles in visual communication and physical interactions within and between species. Yet the origin and influence of ornamentation on speciation and ecology across macroevolutionary time scales remains poorly understood for virtually all animals. Here, we explore correlative evolution of osseous cranial ornaments with large body size in theropod dinosaurs using a phylogenetic comparative framework. We find that body size evolved directionally toward phyletic giantism an order of magnitude faster in theropod species possessing ornaments compared with unadorned lineages. In addition, we find a body mass threshold below which bony cranial ornaments do not originate. Maniraptoriform dinosaurs generally lack osseous cranial ornaments despite repeatedly crossing this body size threshold. Our study provides novel, quantitative support for a shift in selective pressures on socio-sexual display mechanisms in theropods coincident with the evolution of pennaceous feathers. PMID- 27676311 TI - Filter penetration and breathing resistance evaluation of respirators and dust masks. AB - The primary objective of this study was to compare the filter performance of a representative selection of uncertified dust masks relative to the filter performance of a set of NIOSH-approved N95 filtering face-piece respirators (FFRs). Five different models of commercially available dust masks were selected for this study. Filter penetration of new dust masks was evaluated against a sodium chloride aerosol. Breathing resistance (BR) of new dust masks and FFRs was then measured for 120 min while challenging the dust masks and FFRs with Arizona road dust (ARD) at 25 degrees C and 30% relative humidity. Results demonstrated that a wide range of maximum filter penetration was observed among the dust masks tested in this study (3-75% at the most penetrating particle size (p < 0.001). The breathing resistances of the unused FFRs and dust masks did not vary greatly (8-13 mm H2O) but were significantly different (p < 0.001). After dust loading there was a significant difference between the BR caused by the ARD dust layer on each FFR and dust mask. Microscopic analysis of the external layer of each dust mask and FFR suggests that different collection media in the external layer influences the development of the dust layer and therefore affects the increase in BR differently between the tested models. Two of the dust masks had penetration values < 5% and quality factors (0.26 and 0.33) comparable to those obtained for the two FFRs (0.23 and 0.31). However, the remaining three dust masks, those with penetration > 15%, had quality factors ranging between 0.04 0.15 primarily because their initial BR remained relatively high. These results indicate that some dust masks analysed during this research did not have an expected very low BR to compensate for their high penetration. PMID- 27676312 TI - The Harvard organic photovoltaic dataset. AB - The Harvard Organic Photovoltaic Dataset (HOPV15) presented in this work is a collation of experimental photovoltaic data from the literature, and corresponding quantum-chemical calculations performed over a range of conformers, each with quantum chemical results using a variety of density functionals and basis sets. It is anticipated that this dataset will be of use in both relating electronic structure calculations to experimental observations through the generation of calibration schemes, as well as for the creation of new semi empirical methods and the benchmarking of current and future model chemistries for organic electronic applications. PMID- 27676313 TI - DNA-Based Nanopore Sensing. AB - Nanopore sensing is an attractive, label-free approach that can measure single molecules. Although initially proposed for rapid and low-cost DNA sequencing, nanopore sensors have been successfully employed in the detection of a wide variety of substrates. Early successes were mostly achieved based on two main strategies by 1) creating sensing elements inside the nanopore through protein mutation and chemical modification or 2) using molecular adapters to enhance analyte recognition. Over the past five years, DNA molecules started to be used as probes for sensing rather than substrates for sequencing. In this Minireview, we highlight the recent research efforts of nanopore sensing based on DNA mediated characteristic current events. As nanopore sensing is becoming increasingly important in biochemical and biophysical studies, DNA-based sensing may find wider applications in investigating DNA-involving biological processes. PMID- 27676314 TI - Postoperative cognitive dysfunction and its relationship to cognitive reserve in elderly total joint replacement patients. AB - Whether total joint replacement (TJR) patients are susceptible to postoperative cognitive dysfunction (POCD) remains unclear due to inconsistencies in research methodologies. Moreover, cognitive reserve may moderate the development of POCD after TJR, but has not been investigated in this context. The current study investigated POCD after TJR, and its relationship with cognitive reserve, using a more rigorous methodology than has previously been utilized. Fifty-three older adults (aged 50+) scheduled for TJR were assessed pre and post surgery (6 months). Forty-five healthy controls matched for age, gender, and premorbid IQ were re-assessed after an equivalent interval. Cognition, cognitive reserve, and physical and mental health were all measured. Standardized regression-based methods were used to assess cognitive changes, while controlling for the confounding effect of repeated cognitive testing. TJR patients only demonstrated a significant decline in Trail Making Test Part B (TMT B) performance, compared to controls. Cognitive reserve only predicted change in TMT B scores among a subset of TJR patients. Specifically, patients who showed the most improvement pre to post surgery had significantly higher reserve than those who showed the greatest decline. The current study provides limited evidence of POCD after TJR when examined using a rigorous methodology, which controlled for practice effects. Cognitive reserve only predicted performance within a subset of the TJR sample. However, the role of reserve in more cognitively compromised patients remains to be determined. PMID- 27676315 TI - Erratum. PMID- 27676317 TI - Millimeter-Wave Spectroscopy, X-ray Crystal Structure, and Quantum Chemical Studies of Diketene: Resolving Ambiguities Concerning the Structure of the Ketene Dimer. AB - The pure rotational spectrum of diketene has been studied in the millimeter-wave region from ~240 to 360 GHz. For the ground vibrational state and five vibrationally excited satellites (nu24, 2nu24, 3nu24, 4nu24, and nu16), the observed spectrum allowed for the measurement, assignment, and least-squares fitting a total of more than 10 000 distinct rotational transitions. In each case, the transitions were fit to single-state, complete or near-complete sextic centrifugally distorted rotor models to near experimental error limits using Kisiel's ASFIT. Additionally, we obtained less satisfactory least-squares fits to single-state centrifugally distorted rotor models for three additional vibrational states: nu24 + nu16, nu23, and 5nu24. The structure of diketene was optimized at the CCSD(T)/ANO1 level, and the vibration-rotation interaction (alphai) values for each normal mode were determined with a CCSD(T)/ANO1 VPT2 anharmonic frequency calculation. These alphai values were helpful in identifying the previously unreported nu16 and nu23 fundamental states. We obtained a single crystal X-ray structure of diketene at -173 degrees C. The bond distances are increased in precision by more than an order of magnitude compared to those in the 1958 X-ray crystal structure. The improved accuracy of the crystal structure geometry resolves the discrepancy between previous computational and experimental structures. The rotational transition frequencies provided herein should be useful for a millimeter-wave or terahertz search for diketene in the interstellar medium. PMID- 27676318 TI - Socio-economics, food habits and the prevalence of childhood obesity in Spain. AB - BACKGROUND: In 2012, the prevalence of obesity and overweight statuses among children in Spain was 9% and 26%, respectively. Concerns about childhood obesity have increased over the past few years, as obesity developed during childhood can persist throughout an individual's lifetime (cohort effect). This study aims to develop a better understanding of the factors influencing the prevalence of obesity in Spain. METHODS: Microdata from the 2012 National Health Survey are used, and the methodological framework is based on the estimation of a sample selection model. RESULTS: Results suggest that the prevalence of obesity increases among children who live in households of a lower socio-economic status and households in which parents are obese. Lower levels of childhood physical activity are positively related to the probability of being obese. Finally, there exists a positive relationship between children's body mass index and an inappropriate intake of fresh fruits, fish, pasta and rice, legumes, sweets and soft drinks. CONCLUSIONS: The methodological framework used in this study is flexible enough to be used in traditional longitudinal studies. Children's and households' lifestyles play a pivotal role in the prevalence of obesity. Policies should be oriented toward changing lifestyles, which would require more multidisciplinary research in the future to reduce childhood obesity. PMID- 27676316 TI - Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis relies on its own ability to biosynthesize coenzyme A to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the essential pantothenate and coenzyme A biosynthesis pathways have attracted attention as targets for tuberculosis drug development. To identify the optimal step for coenzyme A pathway disruption in M. tuberculosis, we constructed and characterized a panel of conditional knockdown mutants in coenzyme A pathway genes. Here, we report that silencing of coaBC was bactericidal in vitro, whereas silencing of panB, panC, or coaE was bacteriostatic over the same time course. Silencing of coaBC was likewise bactericidal in vivo, whether initiated at infection or during either the acute or chronic stages of infection, confirming that CoaBC is required for M. tuberculosis to grow and persist in mice and arguing against significant CoaBC bypass via transport and assimilation of host-derived pantetheine in this animal model. These results provide convincing genetic validation of CoaBC as a new bactericidal drug target. PMID- 27676319 TI - Risk Assessment in High- and Low-MELD Liver Transplantation. AB - Allocation of liver grafts triggers emotional debates, as those patients, not receiving an organ, are prone to death. We analyzed a high-Model of End-stage Liver Disease (MELD) cohort (laboratory MELD score >=30, n = 100, median laboratory MELD score of 35; interquartile range 31-37) of liver transplant recipients at our center during the past 10 years and compared results with a low MELD group, matched by propensity scoring for donor age, recipient age, and cold ischemia time. End points of our study were cumulative posttransplantation morbidity, cost, and survival. Six different prediction models, including donor age x recipient MELD (D-MELD), Difference between listing MELD and MELD at transplant (Delta MELD), donor-risk index (DRI), Survival Outcomes Following Liver Transplant (SOFT), balance-of-risk (BAR), and University of California Los Angeles-Futility Risk Score (UCLA-FRS), were applied in both cohorts to identify risk for poor outcome and high cost. All score models were compared with a clinical-oriented decision, based on the combination of hemofiltration plus ventilation. Median intensive care unit and hospital stays were 8 and 26 days, respectively, after liver transplantation of high-MELD patients, with a significantly increased morbidity compared with low-MELD patients (median comprehensive complication index 56 vs. 36 points [maximum points 100] and double cost [median US$179 631 vs. US$80 229]). Five-year survival, however, was only 8% less than that of low-MELD patients (70% vs. 78%). Most prediction scores showed disappointing low positive predictive values for posttransplantation mortality, such as mortality above thresholds, despite good specificity. The clinical observation of hemofiltration plus ventilation in high-MELD patients was even superior in this respect compared with D-MELD, DRI, Delta MELD, and UCLA-FRS but inferior to SOFT and BAR models. Of all models tested, only the BAR score was linearly associated with complications. In conclusion, the BAR score was most useful for risk classification in liver transplantation, based on expected posttransplantation mortality and morbidity. Difficult decisions to accept liver grafts in high-risk recipients may thus be guided by additional BAR score calculation, to increase the safe use of scarce organs. PMID- 27676320 TI - Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism. AB - OBJECTIVE: To determine whether headache disorders are a risk factor for the development of new onset hypothyroidism. BACKGROUND: Past studies have reported associations between headache disorders and hypothyroidism, but the directionality of the association is unknown. METHODS: This was a longitudinal retrospective cohort study using data from the Fernald Medical Monitoring Program (FMMP). Residents received physical examinations and thyroid function testing every 3 years during the 20 year program. Residents were excluded from the cohort if there was evidence of past thyroid disease or abnormal thyroid function tests at the first office visit. A diagnosis of a headache disorder was established by self-report of "frequent headaches," use of any headache-specific medication, or a physician diagnosis of a headache disorder. The primary outcome measure was new onset hypothyroidism defined as the initiation of thyroid replacement therapy or TSH >= 10 without thyroid medication. A Cox survival analysis with time dependent variables were used for the model. Headache disorders, age, sex, body mass index, income, smoking, narcotic use, and hypothyroidism-producing medications were independent variables in the model. RESULTS: Data from 8412 residents enrolled in the FMMP were used in the current study. Headache disorders were present in about 26% of the residents and new onset hypothyroidism developed in ~7%. The hazard ratio for the development of new onset hypothyroidism was 1.21 (95% CI = 1.001, 1.462) for those with headache disorders. CONCLUSIONS: Headache disorders may be associated with an increased risk for the development of new onset hypothyroidism. PMID- 27676321 TI - Phosphorylation Mechanism of Phosphomevalonate Kinase: Implications for Rational Engineering of Isoprenoid Biosynthetic Pathway Enzymes. AB - The mevalonate pathway is of important clinical, pharmaceutical, and biotechnological relevance. However, lack of the understanding of the phosphorylation mechanism of the kinases in this pathway has limited rationally engineering the kinases in industry. Here the phosphorylation reaction mechanism of a representative kinase in the mevalonate pathway, phosphomevalonate kinase, was studied by using molecular dynamics and hybrid QM/MM methods. We find that a conserved residue (Ser106) is reorientated to anchor ATP via a stable H-bond interaction. In addition, Ser213 located on the alpha-helix at the catalytic site is repositioned to further approach the substrate, facilitating the proton transfer during the phosphorylation. Furthermore, we elucidate that Lys101 functions to neutralize the negative charge developed at the beta-, gamma bridging oxygen atom of ATP during phosphoryl transfer. We demonstrate that the dissociative catalytic reaction occurs via a direct phosphorylation pathway. This is the first study on the phosphorylation mechanism of a mevalonate pathway kinase. The elucidation of the catalytic mechanism not only sheds light on the common catalytic mechanism of the GHMP kinase superfamily but also provides the structural basis for engineering the mevalonate pathway kinases to further exploit their applications in the production of a wide range of fine chemicals such as biofuels or pharmaceuticals. PMID- 27676322 TI - Addition of different concentrations of prostasome-like vesicles at neutral or slightly alkaline pH decreases canine sperm motility. AB - Prostasome-like vesicles (PV) are components of the canine prostatic fluid during ejaculation and despite some enzymatic activities have been identified recently, their functions in the reproductive events in this species are still poorly understood. In this study, we evaluated at neutral or slightly alkaline pH, the effects of different concentrations of purified PV on sperm cell motility characteristics and the impact on the short- and long-term preservation of preserved semen maintained at room temperature. Two different experiments were performed. In the first experiment, purified PV were added at increasing concentration (1.25, 2.5, 5, 10, and 20 MUL equivalent to 1, 2, 4, 8, and 16 MUg of protein, respectively) to aliquots of 100 MUL of preserved semen maintained at 22 degrees C at the following time points: 0, 30, 60, 120, 240, and 480 min. Computer-assisted sperm motility characteristics and pH were assessed three times at each time points, for each sample and for every concentrations. In the second experiment, the purified PV were added with the same methods as described above but only at time 0. Sperm motility characteristics and pH were assessed over the time. This study showed how the addition of purified PV to preserved semen affects negatively (p < 0.05) at neutral and alkaline pH, both total and progressive motility in a concentration depending manner. Furthermore, prostasome addition was demonstrated to change the quality of sperm movement which may represent a mechanism facilitating sperm cells attachment to the uterine epithelium and facilitating energy preservation before fertilization. PMID- 27676324 TI - Structure and Magnetic Behavior of Layered Honeycomb Tellurates, BiM(III)TeO6 (M = Cr, Mn, Fe). AB - New layered honeycomb tellurates, BiM(III)TeO6 (M = Cr, Mn, Fe) were synthesized and characterized. BiM(III)TeO6 (M = Cr, Fe) species crystallize in a trigonal space group, P31c (No. 163), of edge-sharing M3+/Te6+O6 octahedra, which form honeycomb-like double layers in the ab plane with Bi3+ cations located between the layers. Interestingly, the structure of BiMnTeO6 is similar to those of the Cr/Fe analogues, but with monoclinic space group, P21/c (No. 14), attributed to the strong Jahn-Teller distortion of Mn3+ cations. The crystal structure of BiM(III)TeO6 is a superstructure of PbSb2O6-related materials (ABB'O6). The Cr3+ and Fe3+ cations are ordered 80% and 90%, respectively, while the Mn3+ ions are completely ordered on the B-site of the ABB'O6 structure. BiCrTeO6 shows a broad antiferromagnetic transition (AFM) at ~17 K with a Weiss temperature (theta) of 59.85 K, while BiFeTeO6 and BiMnTeO6 show sharp AFM transitions at ~11 K with theta of -27.56 K and at ~9.5 K with theta of -17.57 K, respectively. These differences in the magnetic behavior are ascribed to the different concentration of magnetic nearest versus next-nearest neighbor interactions of magnetic cations due to the relative differences in the extent of M/Te ordering. PMID- 27676323 TI - Infection Rates of Electrical Leads Used for Percutaneous Neurostimulation of the Peripheral Nervous System. AB - BACKGROUND: Percutaneous neurostimulation of the peripheral nervous system involves the insertion of a wire "lead" through an introducing needle to target a nerve/plexus or a motor point within a muscle. Electrical current may then be passed from an external generator through the skin via the lead for various therapeutic goals, including providing analgesia. With extended use of percutaneous leads sometimes greater than a month, infection is a concern. It was hypothesized that the infection rate of leads with a coiled design is lower than for leads with a noncoiled cylindrical design. METHODS: The literature was retrospectively reviewed for clinical studies of percutaneous neurostimulation of the peripheral nervous system of greater than 2 days that included explicit information on adverse events. The primary endpoint was the number of infections per 1,000 indwelling days. RESULTS: Forty-three studies were identified that met inclusion criteria involving coiled (n = 21) and noncoiled (n = 25) leads (3 studies involved both). The risk of infection with noncoiled leads was estimated to be 25 times greater than with coiled leads (95% confidence interval [CI] 2 to 407, P = 0.006). The infection rates were estimated to be 0.03 (95% CI 0.01 to 0.13) infections per 1,000 indwelling days for coiled leads and 0.83 (95% CI 0.16 to 4.33) infections per 1,000 indwelling days for noncoiled leads (P = 0.006). CONCLUSIONS: Percutaneous leads used for neurostimulation of the peripheral nervous system have a much lower risk of infection with a coiled design compared with noncoiled leads: approximately 1 infection for every 30,000 vs. 1,200 indwelling days, respectively. PMID- 27676326 TI - Tetramethylpyrazine and Astragaloside IV Synergistically Ameliorate Left Ventricular Remodeling and Preserve Cardiac Function in a Rat Myocardial Infarction Model. AB - Tetramethylpyrazine (TMP) and astragaloside IV (AGS-IV) are herbal ingredients that have been demonstrated in animal models to limit infarct size and protect cardiomyocytes in the acute phase of myocardial infarction (MI), yet their long term cardioprotective effects have not been evaluated. In this study, TMP and/or AGS-IV were administrated to rats for 14 days after MI. Echocardiography revealed that the left ventricular (LV) dimensions and cardiac function were preserved in the MI rats with TMP and AGS-IV treatment, compared with untreated MI rats. Moreover, the LV dimensions and cardiac function in the MI rats with TMP and AGS IV cotreatment were comparable with the sham-operated rats. In addition, TMP and AGS-IV synergistically inhibited LV fibrosis by attenuating MI-induced collagen deposition and elevation of transforming growth factor beta1. TMP and AGS-IV, alone or in synergy, enhanced angiogenesis in the infarcted myocardium and reduced cardiac hypertrophy of the remote myocardium after MI. Furthermore, TMP and AGS-IV mutually upregulated the expression of Sonic hedgehog (Shh), Smoothened, and Glioblastoma-2, the receptor and signal transducer of Shh signaling pathway, in the infarcted myocardium. In summary, in the circumstance of the irreversible ischemic injury, the antifibrotic, and pro-angiogenic properties of TMP and AGS-IV on the nonaffected tissues contribute to the cardioprotection in the healing phase post MI, and the cardioprotective effects are likely to be mediated through the Shh pathway. PMID- 27676325 TI - The Effect of Chronic Activation of the Novel Endocannabinoid Receptor GPR18 on Myocardial Function and Blood Pressure in Conscious Rats. AB - Although acute activation of the novel endocannabinoid receptor GPR18 causes hypotension, there are no reports on GPR18 expression in the heart or its chronic modulation of cardiovascular function. In this study, after demonstrating GPR18 expression in the heart, we show that chronic (2 weeks) GPR18 activation with its agonist abnormal cannabidiol (abn-cbd; 100 ug.kg.d; i.p) produced hypotension, suppressed the cardiac sympathetic dominance, and improved left ventricular (LV) function (increased the contractility index dp/dtmax and reduced LV end-diastolic pressure, LVEDP) in conscious rats. Ex vivo studies revealed increased: (1) cardiac and plasma adiponectin (ADN) levels; (2) vascular (aortic) endothelial nitric oxide synthase (eNOS) expression, (3) vascular and serum nitric oxide (NO) levels; (4) myocardial and plasma cyclic guanosine monophosphate (cGMP) levels; (5) phosphorylation of myocardial protein kinase B (Akt) and extracellular signal regulated kinase 1/2 (ERK1/2) along with reduced myocardial reactive oxygen species (ROS) in abn-cbd treated rats. These biochemical responses contributed to the hemodynamic responses and were GPR18-mediated because concurrent treatment with the competitive GPR18 antagonist (O-1918) abrogated the abn-cbd-evoked hemodynamic and biochemical responses. The current findings present new evidence for a salutary cardiovascular role for GPR18, mediated, at least partly, via elevation in the levels of adiponectin. PMID- 27676327 TI - Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia. AB - 5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg.kg.d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 MUg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 MUg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 MUg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB 258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19 induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor. PMID- 27676328 TI - Unrecognized Cognitive Impairment and Its Effect on Heart Failure Readmissions of Elderly Adults. AB - OBJECTIVES: To determine whether 30-day readmissions were associated with presence of cognitive impairment more in elderly adults with heart failure (HF) than in those with other diagnoses and whether medical teams recognized cognitive impairment. DESIGN: One-year prospective cohort quality improvement program of cognitive screening and retrospective chart review of documentation and outcomes. SETTING: Academic tertiary care hospital medical unit with a cardiovascular focus and an enhanced discharge program of individualized patient education. PARTICIPANTS: Individuals aged 70 and older screened before home discharge (241 admission encounters; 121 with HF as a primary diagnosis, 120 without). The HF cohort included individuals with preserved and reduced ejection fraction. Individuals who had undergone transplantation, ventricular assist device implantation, or hemodialysis or who had a primary oncology diagnosis or hospice referral were excluded. MEASUREMENTS: Mini-Cog administered 48 hours or less before discharge, 30-day all-cause readmission rates, documentation of dementia or cognitive impairment, and caregiver education. RESULTS: Mini-Cog scores were less than 4 (indicating cognitive impairment) in 157 encounters (82 (67.7%) with HF, 75 (62.5%) without). Mini-Cog scores were similar in rate and distribution between groups. Individuals with HF and cognitive impairment had a significantly higher 30-day readmission rate than did the other groups (26.8% vs 13.2%; P = .01; HF, no cognitive impairment, 12.8%; no HF, no cognitive impairment, 13.3%; cognitive impairment, no HF, 13.3%). In individuals with HF and cognitive impairment, those with documented caregiver education had lower readmission rates than those without (14.3% vs 36.2%; P = .03). Fewer than 9% had documentation of cognitive impairment in the medical record. CONCLUSION: Cognitive impairment, which is frequently undocumented, may indicate greater risk of readmission for individuals with HF than those without. Screening for cognitive impairment, adapting discharge for it, and involving family and caregivers in discharge education may help reduce readmissions. PMID- 27676329 TI - [Clinical Results after Implantation of Epiretinal Visual Prostheses]. AB - Epiretinal visual prostheses have already been implanted in blind retinitis pigmentosa (RP) patients. Here we report on clinical experience with the Argus(r) II device and the EPIRET 3 device, on the basis of data from patients operated in Germany. Twenty-eight patients were implanted with the Argus II device and followed for up to three years. EPIRET 3 was implanted in six patients for a period of four weeks. With Argus II, an improvement in visual performance was achieved in the majority of cases, as demonstrated by improved localisation of a light spot and a better perception of moving targets. Mobility and self confidence improved. The main complications were conjunctival erosion due to the combined extra- and intraocular concept of the device. Among the 28 implanted systems, two needed to be removed because complications refractive to treatment. In contrast, EPIRET 3 is a fully intraocular epiretinal system. During a four week implantation, period thresholds were recorded and exhibited high variability between subjects. However, patients were able to recognise simple patterns. Epiretinal implants for electrical stimulation of the retina should be considered to treat advanced photoreceptor degeneration, and thus to restore basic visual functions at an acceptable rate of complications. PMID- 27676330 TI - [Optic Nerve Head Diagnostics with Optical Coherence Tomography]. AB - BACKGROUND: With a cooperative patient, examination of the optic nerve head using optical coherence tomography (OCT) is fast and easy to perform and facilitates identification and monitoring of different pathological changes in the optic nerve head. MATERIALS AND METHODS: Characteristic findings and scanning options are illustrated using case examples to simplify recognition of infrequent diseases of the optic nerve head and to facilitate treatment decisions using OCT results. RESULTS: Pathological changes and characteristic OCT findings are shown for glaucoma, for different anomalies of the optic nerve head, for non glaucomatous optic atrophies and for optic disc swelling for different reasons. The most suitable OCT parameters and examination modes are listed to differentiate between specific pathological changes. CONCLUSION: Optic nerve head examination using the OCT facilitates rapid diagnosis of infrequent and hard to distinguish pathological changes, as well as exact monitoring of chronic progressive diseases of the optic nerve. Correct application and evaluation of results gathered using OCT examination of the optic nerve head facilitates accurate diagnosis and correct decisions. PMID- 27676331 TI - Chemical Forms of Mercury in Human Hair Reveal Sources of Exposure. AB - Humans are contaminated by mercury in different forms from different sources. In practice, contamination by methylmercury from fish consumption is assessed by measuring hair mercury concentration, whereas exposure to elemental and inorganic mercury from other sources is tested by analysis of blood or urine. Here, we show that diverse sources of hair mercury at concentrations as low as 0.5 ppm can be individually identified by specific coordination to C, N, and S ligands with high energy-resolution X-ray absorption spectroscopy. Methylmercury from seafood, ethylmercury used as a bactericide, inorganic mercury from dental amalgams, and exogenously derived atmospheric mercury bind in distinctive intermolecular configurations to hair proteins, as supported by molecular modeling. A mercury spike located by X-ray nanofluorescence on one hair strand could even be dated to removal of a single dental amalgam. Chemical forms of other known or putative toxic metals in human tissues could be identified by this approach with potential broader applications to forensic, energy, and materials science. PMID- 27676332 TI - Effect of dibutyl phthalate on expression of connexin 43 and testosterone production of leydig cells in adult rats. AB - To investigate the adverse effect of dibutyl phthalate (DBP) on Leydig cells and its mechanism related to gap junction, Leydig cells isolated from adult rats were treated with 0.1% dimethylsulfoxide (DMSO), 50mg/L DBP, 50mg/L DBP+10MUM prostaglandin E2 (PGE2) and 40MUM flutamide respectively. Radioimmunoassay, semi quantitative RT-PCR, immunofluorescence and Western blot were applied to determine the expression of testosterone and Connexin 43 (Cx43) in Leydig cells. The expression of testosterone and Cx43 were both decreased in DBP group (P<0.05). While Cx43 was up-regulated after administered to PGE2, there was no significant change in testosterone. However, testosterone was down-regulated with a significant decrease of Cx43 in flutamide group. The results indicated that the inhibitory effect of DBP on testosterone production was not through the down regulation of Cx43. On the contrary, the change of testosterone can influence the expression of Cx43 in Leydig cells. PMID- 27676334 TI - Alcohol Involvement in Homicide Victimization in the United States. AB - BACKGROUND: Although the association between alcohol and homicide is well documented, there has been no recent study of alcohol involvement in homicide victimization in U.S. states. The objective of this article was to determine the prevalence of alcohol involvement in homicide victimization and to identify socio demographic and other factors associated with alcohol involvement in homicide victimization. METHODS: Data from homicide victims with a reported blood alcohol content (BAC) level were analyzed from 17 states from 2010 to 2012 using the National Violent Death Reporting System. Logistic regression was used to investigate factors associated with the odds of homicide victims having a BAC >= 0.08%. RESULTS: Among all homicide victims, 39.9% had a positive BAC including 13.7% with a BAC between 0.01% and 0.79% and 26.2% of victims with a BAC >= 0.08%. Males were twice as likely as females to have a BAC >= 0.08% (29.1% vs. 15.2%; p < 0.001). Characteristics that were independent predictors of homicide victims having a BAC >= 0.08 included male sex, American Indian/Alaska Native race, Hispanic ethnicity, history of intimate partner violence, and nonfirearm homicides. CONCLUSIONS: Alcohol is present in a substantial proportion of homicide victims in the United States, with substantial variation by state, demographic, and circumstantial characteristics. Future studies should explore the relationships between state-level alcohol policies and alcohol involvement among perpetrators and victims of homicide. PMID- 27676335 TI - Time for global political action on antimicrobial resistance. PMID- 27676336 TI - Zika virus and global health security. PMID- 27676333 TI - Tau downregulates BDNF expression in animal and cellular models of Alzheimer's disease. AB - In Alzheimer's disease, soluble tau accumulates and deposits as neurofibrillary tangles (NFTs). However, a precise toxic mechanism of tau is not well understood. We hypothesized that overexpression of wild-type tau downregulates brain-derived neurotrophic factor (BDNF), a neurotrophic peptide essential for learning and memory. Two transgenic mouse models of human tau expression and human tau (hTau40)-transfected human neuroblastoma (SH-SY5Y) cells were used to examine the effect of excess or pathologically modified wild-type human tau on BDNF expression. Both transgenic mouse models, with or without NFTs, as well as hTau40 SH-SY5Y cells significantly downregulated BDNF messenger RNA compared with controls. Similarly, transgenic mice overexpressing amyloid-beta (Abeta) significantly downregulated BDNF expression. However, when crossed with tau knockout mice, the resulting animals exhibited BDNF levels that were not statistically different from wild-type mice. These results demonstrate that excess or pathologically modified wild-type human tau downregulates BDNF and that neither a mutation in tau nor the presence of NFTs is required for toxicity. Moreover, our findings suggest that tau at least partially mediates Abeta-induced BDNF downregulation. Therefore, Alzheimer's disease treatments targeting Abeta alone may not be effective without considering the impact of tau pathology on neurotrophic pathways. PMID- 27676337 TI - Low risk of a sexually-transmitted Zika virus outbreak. PMID- 27676338 TI - China bans colistin as a feed additive for animals. PMID- 27676339 TI - A hepatitis B-free generation in China: from dream to reality. PMID- 27676340 TI - Zika virus in semen and spermatozoa. PMID- 27676341 TI - Zika virus in semen: lessons from Ebola. PMID- 27676342 TI - Probable sexual transmission of Zika virus from a vasectomised man. PMID- 27676343 TI - Should testing of donors be restricted to active Zika virus areas? PMID- 27676344 TI - Overlooking the importance of immunoassays. PMID- 27676345 TI - Overlooking the importance of immunoassays - Authors' reply. PMID- 27676346 TI - Sertraline for HIV-associated cryptococcal meningitis. PMID- 27676347 TI - Sertraline for HIV-associated cryptococcal meningitis - Authors' reply. PMID- 27676348 TI - Rickettsia felis: the next mosquito-borne outbreak? PMID- 27676349 TI - Finding undiagnosed leprosy cases. PMID- 27676350 TI - Global burden on neglected tropical diseases. PMID- 27676352 TI - Obituary-Donald Ainslie Henderson. PMID- 27676351 TI - Moves to consign rabies to history. PMID- 27676353 TI - FDA approves broad hepatitis C treatment. PMID- 27676356 TI - Polymorphic keratotic nodules in an immunocompetent man. PMID- 27676357 TI - Spin-Orbit Effects, VSEPR Theory, and the Electronic Structures of Heavy and Superheavy Group IVA Hydrides and Group VIIIA Tetrafluorides. A Partial Role Reversal for Elements 114 and 118. AB - Relativistic effective core potentials and spin-orbit operators are used in relativistic configuration interaction calculations to explore the effects of spin-orbit coupling on the electronic structures of atoms and molecules of elements 114 and 118. The monohydrides of group IVA and the tetrafluorides of group VIIIA are examined in order to provide examples of trends within families among the various periods. The spin-orbit effect is found to play a dominant role in the determination of atomic and molecular properties. Several nonintuitive consequences of spin-orbit coupling are presented, including the depiction of element 114 as a closed-shell "noble" atom and the suggestion that the VSEPR theory is inadequate to describe the geometry of the rare gas tetrafluoride, (118)F4. PMID- 27676358 TI - Water-Induced Structural Changes in Crown Ethers from Broadband Rotational Spectroscopy. AB - The complexes of 12-crown-4 ether (12C4) with water, generated in a supersonic jet, have been studied using broadband Fourier transform microwave spectroscopy. Three 1:1 and one 1:2 clusters have been observed and their structures unambiguously identified through the observation of isotopologue spectra. The structures of the clusters are based on networks of O-H...O and C-H...O hydrogen bonds. The most abundant 1:1 cluster is formed from the most stable S4 symmetry conformer of 12C4, even though it is not the energetically favored water complex. Interestingly, the structures of the most stable water cluster and the other remaining observed 1:1 and 1:2 complexes are formed from the second or the fifth most abundant conformers of 12C4. This shows the existence of a mechanism that changes the conformation of 12C4 so that the host-guest interactions can be maximized, even for a "soft" ligand like water. PMID- 27676360 TI - mirVAFC: A Web Server for Prioritizations of Pathogenic Sequence Variants from Exome Sequencing Data via Classifications. AB - Exome sequencing has been widely used to identify the genetic variants underlying human genetic disorders for clinical diagnoses, but the identification of pathogenic sequence variants among the huge amounts of benign ones is complicated and challenging. Here, we describe a new Web server named mirVAFC for pathogenic sequence variants prioritizations from clinical exome sequencing (CES) variant data of single individual or family. The mirVAFC is able to comprehensively annotate sequence variants, filter out most irrelevant variants using custom criteria, classify variants into different categories as for estimated pathogenicity, and lastly provide pathogenic variants prioritizations based on classifications and mutation effects. Case studies using different types of datasets for different diseases from publication and our in-house data have revealed that mirVAFC can efficiently identify the right pathogenic candidates as in original work in each case. Overall, the Web server mirVAFC is specifically developed for pathogenic sequence variant identifications from family-based CES variants using classification-based prioritizations. The mirVAFC Web server is freely accessible at https://www.wzgenomics.cn/mirVAFC/. PMID- 27676359 TI - Chronic subordinate colony housing paradigm: A mouse model for mechanisms of PTSD vulnerability, targeted prevention, and treatment-2016 Curt Richter Award Paper. AB - There is considerable individual variability in vulnerability for developing posttraumatic stress disorder (PTSD); evidence suggests that this variability is related in part to genetic and environmental factors, including adverse early life experience. Interestingly, recent studies indicate that induction of chronic low-grade inflammation may be a common mechanism underlying gene and environment interactions that increase the risk for development of PTSD symptoms, and, therefore, may be a target for novel interventions for prevention or treatment of PTSD. Development of murine models with face, construct, and predictive validity would provide opportunities to investigate in detail complex genetic, environmental, endocrine, and immunologic factors that determine vulnerability to PTSD-like syndromes, and furthermore may provide mechanistic insight leading to development of novel interventions for both prevention and treatment of PTSD symptoms. Here we describe the potential use of the chronic subordinate colony housing (CSC) paradigm in mice as an adequate animal model for development of a PTSD-like syndrome and describe recent studies that suggest novel interventions for the prevention and treatment of PTSD. PMID- 27676361 TI - Influence of long-range atmospheric transport pathways and climate teleconnection patterns on the variability of surface 210Pb and 7Be concentrations in southwestern Europe. AB - The variability of the atmospheric concentration of the 7Be and 210Pb radionuclides is strongly linked to the origin of air masses, the strength of their sources and the processes of wet and dry deposition. It has been shown how these processes and their variability are strongly affected by climate change. Thus, a deeper knowledge of the relationship between the atmospheric radionuclides variability measured close to the ground and these atmospheric processes could help in the analysis of climate scenarios. In the present study, we analyze the atmospheric variability of a 14-year time series of 7Be and 210Pb in a Mediterranean coastal city using a synergy of different indicators and tools such as: the local meteorological conditions, global and regional climate indexes and a lagrangian atmospheric transport model. We particularly focus on the relationships between the main pathways of air masses and sun spots occurrence, the variability of the local relative humidity and temperature conditions, and the main modes of regional climate variability, such as the North Atlantic Oscillation (NAO) and the Western Mediterranean Oscillation (WeMO). The variability of the observed atmospheric concentrations of both 7Be and 210Pb radionuclides was found to be mainly positively associated to the local climate conditions of temperature and to the pathways of air masses arriving at the station. Measured radionuclide concentrations significantly increase when air masses travel at low tropospheric levels from central Europe and the western part of the Iberian Peninsula, while low concentrations are associated with westerly air masses. We found a significant negative correlation between the WeMO index and the atmospheric variability of both radionuclides and no significant association was observed for the NAO index. PMID- 27676362 TI - Home-Based Exercise Supported by General Practitioner Practices: Ineffective in a Sample of Chronically Ill, Mobility-Limited Older Adults (the HOMEfit Randomized Controlled Trial). AB - OBJECTIVES: To evaluate the effects a home-based exercise program delivered to ill and mobility-limited elderly individuals on physical function, physical activity, quality of life, fall-related self-efficacy, and exercise self efficacy. DESIGN: Randomized controlled trial (ISRCTN Registry, Reg.-No. ISRCTN17727272). SETTING: Fifteen general practitioner (GP) practices and participants' homes. PARTICIPANTS: Chronically ill and mobility-limited individuals aged 70 and older (N = 209). INTERVENTIONS: An exercise therapist delivered the experimental intervention-a 12-week multidimensional home-based exercise program integrating behavioral strategies-in individual counseling sessions at the GPs' practices and over the telephone. The control intervention focused on promoting light-intensity activities of daily living. Interventions took place between February 2012 and March 2013. MEASUREMENTS: The primary outcome was functional lower body strength (chair-rise test). Secondary outcomes were physical function (battery of motor tests), physical activity (step count), health-related quality of life (Medical Outcomes Study 8-item Short-Form Survey), fall-related (Falls Efficacy Scale-International Version), and exercise self efficacy (Selbstwirksamkeit zur sportlichen Aktivitaet (SSA) scale). Postintervention differences between the groups were tested using analysis of covariance (intention to treat; adjusted for baseline value and GP practice; significance level P <= .05). RESULTS: Participants had a mean age +/- standard deviation of 80 +/- 5, 74% were female, 87% had three or more chronic diseases, and 54% used a walking aid. The difference (intention to treat; experimental minus control) between adjusted postintervention chair-rise times was -0.1 (95% confidence interval = -1.8-1.7). Differences for all secondary outcomes were also nonsignificant. CONCLUSION: The program was ineffective in the target population. Possibilities for improving the concept will have to be evaluated. PMID- 27676363 TI - Genomic alterations in small cell lung cancer and their clinical relevance. PMID- 27676364 TI - Tetra- and Octapyrroles Synthesized from Confusion and Fusion Approaches. AB - By oxidation of an alternately N-confused bilane in CH2Cl2, a C-N fused tetrapyrrin was synthesized that bears a 5.5.5-tricyclic ring generated from an intramolecular C-N linkage. When CH3CN was used as the reaction medium, a multiply C-N-fused octapyrrolic dimer was also obtained that contained two 5.5.5.7.5-pentacyclic moieties and a bipyrrole unit generated from the intramolecular C-N linkage and intermolecular C-C linkage, respectively. This could be coordinated with Ni(acac)2 to afford a mixed-ligand complex. PMID- 27676365 TI - Fluorine and microorganisms: An annotated selection of world wide web sites relevant to the topics in environmental microbiology. PMID- 27676366 TI - Multimethod prediction of child abuse risk in an at-risk sample of male intimate partner violence offenders. AB - The vast majority of research on child abuse potential has concentrated on women demonstrating varying levels of risk of perpetrating physical child abuse. In contrast, the current study considered factors predictive of physical child abuse potential in a group of 70 male intimate partner violence offenders, a group that would represent a likely high risk group. Elements of Social Information Processing theory were evaluated, including pre-existing schemas of empathy, anger, and attitudes approving of parent-child aggression considered as potential moderators of negative attributions of child behavior. To lend methodological rigor, the study also utilized multiple measures and multiple methods, including analog tasks, to predict child abuse risk. Contrary to expectations, findings did not support the role of anger independently predicting child abuse risk in this sample of men. However, preexisting beliefs approving of parent-child aggression, lower empathy, and more negative child behavior attributions independently predicted abuse potential; in addition, greater anger, poorer empathy, and more favorable attitudes toward parent-child aggression also exacerbated men's negative child attributions to further elevate their child abuse risk. Future work is encouraged to consider how factors commonly considered in women parallel or diverge from those observed to elevate child abuse risk in men of varying levels of risk. PMID- 27676368 TI - Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism. AB - The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from sulfophenyl acetic amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs. X-ray crystallography reveals that binding of SPAA-based inhibitors induces a striking conformational change in the LMW-PTP active site, leading to the formation of a previously undisclosed hydrophobic pocket to accommodate the alpha-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity. PMID- 27676367 TI - A Population-Based Study of Four Genes Associated with Heroin Addiction in Han Chinese. AB - Recent studies have shown that variants in FAT atypical cadherin 3 (FAT3), kinectin 1 (KTN1), discs large homolog2 (DLG2) and deleted in colorectal cancer (DCC) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with heroin addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method. A total of 1080 samples, comprising 523 cases and 557 controls, were analyzed. We observed that DCC rs16956878, rs12607853, and rs2292043 were associated with heroin addiction. The T alleles of rs16956878 (p = 0.0004) and rs12607853 (p = 0.002) were significantly enriched in the case group compared with the controls. A lower incidence of the C allele of rs2292043 (p = 0.002) was observed in the case group. In block 2 of DCC (rs2292043-rs12607853 rs16956878), the frequency of the T-T-T haplotype was significantly higher in the case group than in the control group (p = 0.024), and fewer C-C-C haplotypes (p = 0.006) were detected in the case group. DCC may be an important candidate gene in heroin addiction, and rs16956878, rs12607853, and rs2292043 may be risk factors, thereby providing a basis for further genetic and biological research. PMID- 27676369 TI - Primary Care Provider and Patient Perspectives on Lung Cancer Screening. A Qualitative Study. AB - RATIONALE: The U.S. Preventive Services Task Force recommends annual low-dose computed tomography (LDCT) for lung cancer screening in high-risk individuals. Preventive healthcare is provided predominantly by primary care providers (PCPs). Successful implementation of a screening program requires acceptance and participation by both providers and patients, with available collaboration with pulmonologists. OBJECTIVES: To identify perceptions of and perspectives on lung cancer screening and implementation among PCPs and eligible veteran patients at high risk for lung cancer. METHODS: We conducted a qualitative study using grounded theory in which 28 veterans and 13 PCPs completed a questionnaire and participated in focus groups. Sessions were recorded, transcribed verbatim, and analyzed with NVivo 10 software. Counts and percentages were used to report questionnaire results. MEASUREMENTS AND MAIN RESULTS: While 58% percent of providers were aware of lung cancer screening guidelines, many could not recall the exact patient eligibility criteria. Most patients were willing to undergo LDCT screening and identified smoking as a risk factor for lung cancer, but they did not recall their PCP explaining the reason for the testing. All providers assessed smoking behavior, but only 23% referred active smokers for formal cessation services. Patients volunteered information regarding their hurdles with smoking cessation while discussing risk factors for cancer. PCPs cited time constraints as a reason for lack of appropriate counseling and shared decision making. Both parties were willing to explore modalities and decision aid tools to improve shared decision making; however, while patients were interested in individual risk prediction, few PCPs believed statistical approaches to counseling would confuse patients. CONCLUSIONS: While patients and providers are receptive to LDCT screening, efforts are needed to improve guideline knowledge and adherence among providers. System-level interventions are necessary to facilitate time and resources for shared decision making and smoking cessation counseling and treatment. Further research is needed to identify optimal strategies for effective lung cancer screening in the community. PMID- 27676370 TI - The Experience of Patients Engaged in Co-designing Care Processes. AB - This article presents the experiences of patients engaged in co-designing care under a program entitled, "Transforming Care at the Bedside," based at an academic health sciences center. This descriptive, qualitative study collected data through individual interviews. Participants included patients from 5 units in an academic health sciences center in Quebec, Canada. A total of 6 individual interviews were conducted in November 2014, 15 months after the Transforming Care at the Bedside work began in September 2013. Content analysis was used to analyze the qualitative data. Being listened to and informed gave patients an opportunity to better understand patient needs and the complexity of care in the unit and in the organization. The experience enabled patients to better translate the patient experience for the team's benefit and influence the team's perspective and decisions. Through this experience, several patients felt motivated and empowered and that they afforded consideration through this experience. This study highlights the importance of creating opportunities for patients and health care providers to share their unique experiences and expertise to better understand each other's reality. In this context, they developed a more comprehensive understanding of the issues and worked together to implement realistic changes on behalf of the patients. PMID- 27676372 TI - Wetting Characteristics of Plasma-Modified Porous Polyethylene. AB - This paper examines the wetting characteristics of porous polyethylene surfaces modified by exposure to reactive oxygen glow discharge gas plasma, through the direct measurement of the wicking properties of the modified material. It is well known that oxygen plasma can be used to chemically alter the surface of polyethylene to enhance wetting properties. Chemical and physical modification of a polymer's surface is the consequence of reactions initiated by the collision of high-energy species in the plasma with the polymer surface. The conditions of the plasma treatment, such as electric field strength (power), exposure time, and chamber pressure, govern the frequency and energy of collisions and, thus, determine the nature and degree of the chemical modification of the polyethylene surface. Comparisons of the chemical modification of sintered porous polyethylene surfaces achieved through treatments with reactive oxygen glow discharge gas plasmas generated at various powers, chamber pressures, and times of exposure were made by measuring the wicking rate of distilled and deionized water in the modified materials. A strong correlation was observed between the electric field power used to generate the plasma and the degree of chemical modification of the polyethylene surfaces. In addition, the rate of chemical modification was also found to be a function of the electric field power. PMID- 27676371 TI - Improving Primary Care Retention in Medically Underserved Areas: What's a Clinic to Do? AB - To reduce health professional shortage areas, the National Health Service Corps has attempted to increase the number of primary care providers in underserved communities through scholarships and loan repayment. Program evaluations assessed Loan Repayment Program (LRP) propensity to work in underserved communities. The National Health Service Corps LRPs were asked about preferences for particular retention strategies and which strategies were utilized by their clinical sites. Loan Repayment Programs were asked to rank retention strategies. Loan Repayment Program top choices were competitive salary, 88%; professional development, 70%; knowledgeable/competent support staff, 59%, and professional support, 58%. Loan Repayment Programs were also asked to rank retention strategies provided by their clinical sites: professional development, 74.2%; competitive salary, 71.2%; policies that prohibit abusive behavior, 63.6%, and knowledgeable/competent support staff, 60.6%. Loan Repayment Programs indicated professional support was an important retention element. However, when asked if professional support opportunities were offered, LRP indicated that these were not in the strategies offered by sites. PMID- 27676373 TI - Emerging microfluidic devices for cancer cells/biomarkers manipulation and detection. AB - Circulating tumour cells (CTCs) are active participants in the metastasis process and account for ~90% of all cancer deaths. As CTCs are admixed with a very large amount of erythrocytes, leukocytes, and platelets in blood, CTCs are very rare, making their isolation, capture, and detection a major technological challenge. Microfluidic technologies have opened-up new opportunities for the screening of blood samples and the detection of CTCs or other important cancer biomarker proteins. In this study, the authors have reviewed the most recent developments in microfluidic devices for cells/biomarkers manipulation and detection, focusing their attention on immunomagnetic-affinity-based devices, dielectrophoresis-based devices, surface-plasmon-resonance microfluidic sensors, and quantum-dots-based sensors. PMID- 27676374 TI - Elucidation of biogenic silver nanoparticles susceptibility towards Escherichia coli: an investigation on the antimicrobial mechanism. AB - Elucidation of the role of silver nanoparticles (AgNPs) in combating bacterial infection is important for the development of new antimicrobial compounds. In this study, several key factors underlying biological effects of biogenic AgNPs were investigated on recombinant Escherichia coli (XL1-Blue) which contains a reporter gene encoding beta-galactosidase enzyme. Biogenic AgNPs were prepared from the tea decoction. Cytotoxicity effects were profound on the bacteria tested by the synthesised NPs. The beta-galactosidase activity of the released intracellular proteins in the supernatant of E. coli was used as a measure of membrane damage and cellular leakage. Occurrence of a significant amount of beta galactosiadase activity in the supernatant of treated cells clearly demonstrated the formation of holes in the bacterial membrane. Scanning electron microscope pictures visibly indicated destruction of the membrane of the bacteria, which further confirmed membrane damage. The synthesised NPs caused damage of E. coli genomic DNA in a dose dependent manner. PMID- 27676375 TI - Green synthesis, characterisation and biological evaluation of AgNPs using Agave americana, Mentha spicata and Mangifera indica aqueous leaves extract. AB - The current study was performed to synthesize stable, eco-friendly and bio compatible silver nano-particles (AgNPs) of Agave americana, Mentha spicata and Mangifera indica leaves and to screen them for biological activities. The ultraviolet-visible spectroscopic analysis revealed that lambda-max for AgNPs range from 350-500 nm. All AgNPs possessed polycrystalline structure as notified as intense graphical peaks in complete spectrum of 20 values ranging from 10-80 degrees in X-ray diffraction measurements and supported by scanning electron microscopy data. The size of the nano-particles was confirmed by transmission electron microscopy (30-150 nm). Mass loss at variable temperatures was evaluated by simultaneous thermogravimetric and differential thermal analysis revealed reduction in mass and activity of compounds was notified by temperature increase from 200 to 800 degrees C, thus concluding it as thermally sensitive compounds. A. americana AgNPs showed significant (96%) activity against Methicillin resistant Staphylococcus aureus, Escherichia coli (95%) and Fusarium oxysporum (89%). Good antioxidant activity was shown by M. spicata AgNPs at 300 ul (79%). M. indica AgNPs showed significant phytotoxic activity (88%) at highest concentration. No haemagglutination reaction was observed for the test samples. The above results revealed that AgNPs synthesized from selected plant species possesses significant antimicrobial and phytotoxic effect. PMID- 27676376 TI - Green synthesis of silver nanoparticles using Zea mays and exploration of its biological applications. AB - The biosynthesis of silver nanoparticles (AgNPs) has been proved to be a cost effective and environmental friendly approach toward chemical and physical methods. In the present study, biosynthesis of AgNPs was carried out using aqueous extract of Zea mays (Zm) husk. The initial colour change from golden yellow to orange was observed between 410 and 450 nm which confirmed the synthesis of AgNPs. Also, dynamic light scattering-particle size analysis confirmed the average size to be 113 nm and zeta potential value of -28 kV. The morphology of synthesised ZmAgNPs displayed flower-shaped structure, X-ray diffraction pattern revealed the strongest peaks at 2theta = 38.6 degrees and 64 degrees which proved that the nanoparticle has the face centred crystalline structure. The Fourier transform infrared spectroscopy results showed strong absorption bands at 1394.53, 2980.02 and 2980.02 cm-1 due to the presence of alkynes, carboxylic acids, alcoholic and phenolic groups. The maximum zone of inhibition was observed against Salmonella typhi (22 mm) and Candida albicans (18 mm). The synthesised nanoparticles exhibited more free radical scavenging activity than the aqueous plant extract. This is the first report on the synthesis of AgNP from Zm husk, delivers the efficient and stable ZmAgNPs through simple feasible approach toward green biotechnology. PMID- 27676377 TI - Role of catalytic protein and stabilising agents in the transformation of Ag ions to nanoparticles by Pseudomonas aeruginosa. AB - Biological routes of synthesising metal nanoparticles (NPs) using microbes have been gaining much attention due to their low toxicity and eco-friendly nature. Pseudomonas aeruginosa JP2 isolated from metal contaminated soil was evaluated towards extracellular synthesis of silver NPs (AgNPs). Cell-free extract (24 h) of the bacterial isolate was reacted with AgNO3 for 24 h in order to fabricate AgNPs. Preliminary observations were recorded in terms of colour change of the reaction mixture from yellow to greyish black. UV-visible spectroscopy of the reaction mixture has shown a progressive increase in optical densities that correspond to peaks near 430 nm, depicting reduction of ionic silver (Ag+) to atomic silver (Ag0) thereby synthesising NPs. X-ray diffraction spectra exhibited the 2theta values to be 38.4577 degrees confirming the crystalline and spherical nature of NPs [9.6 - 26.7 (Ave. = 17.2 nm)]. Transmission electron microscopy finally confirmed the size of the particles varying from 5 to 60 nm. Moreover, rhamnolipids and proteins were identified as stabilising molecules for the AgNPs through Fourier transform-infrared spectroscopy. Characterisation of bacterial crude and purified protein fractions confirmed the involvement of nitrate reductase (molecular weight 66 kDa and specific activity = 3.8 U/mg) in the Synthesis of AgNPs. PMID- 27676378 TI - Green synthesis of nanosilver-decorated graphene oxide sheets. AB - A green facile method has been successfully used for the synthesis of graphene oxide sheets decorated with silver nanoparticles (rGO/AgNPs), employing graphite oxide as a precursor of graphene oxide (GO), AgNO3 as a precursor of Ag nanoparticles (AgNPs), and geranium (Pelargonium graveolens) extract as reducing agent. Synthesis was accomplished using the weight ratios 1:1 and 1:3 GO/Ag, respectively. The synthesised nanocomposites were characterised by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, X ray diffraction, UV-visible spectroscopy, Raman spectroscopy, energy dispersive X ray spectroscopy and thermogravimetric analysis. The results show a more uniform and homogeneous distribution of AgNPs on the surface of the GO sheets with the weight ratio 1:1 in comparison with the ratio 1:3. This eco-friendly method provides a rGO/AgNPs nanocomposite with promising applications, such as surface enhanced Raman scattering, catalysis, biomedical material and antibacterial agent. PMID- 27676379 TI - Postprandial anti-hyperglycemic activity of marine Streptomyces coelicoflavus SRBVIT13 mediated gold nanoparticles in streptozotocin induced diabetic male albino Wister rats. AB - The present study focuses on the biosynthesis of gold nanoparticles (AuNPs) using Streptomyces coelicoflavus (S. coelicoflavus) SRBVIT13 isolated from marine salt pan soils collected from Ongole, Andhra Pradesh, India. The biosynthesised AuNPs are characterised by UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, high-resolution transmission electron microscopy and energy-dispersive X-ray analysis. Transmission electron microscopy study suggests that the biosynthesised AuNPs are spherical in shape within a size range of 12-20 nm (mean diameter as 14 nm). The anti-type II diabetes activity of AuNPs is carried out by testing it in vitro alpha-glucosidase and alpha-amylase enzyme inhibition activity and in vivo postprandial anti-hyperglycemic activity in sucrose and glucose-loaded streptozotocin induced diabetic albino Wister rats. AuNPs has shown a significant inhibitory activity of 84.70 and 87.82% with IC50 values of 67.65 and 65.59 MUg/mL to alpha-glucosidase and alpha-amylase enzymes, while the diabetic rats have shown significant reduction in the post postprandial blood glucose level by 57.80 and 88.09%, respectively compared with control group after AuNPs treatment at the concentration of 300 and 600 mg/kg body weight. Hence, this biosynthesised AuNPs might be useful in combating type II diabetes mellitus for the betterment of human life. PMID- 27676380 TI - Low noise patch-clamp current amplification by nanoparticles plasmonic-photonic coupling (analysis and modelling). AB - In this article, a patch-clamp low noise current amplification based on nanoparticles plasmonic radiation is analyzed. It is well-known, a very small current is flowing from different membrane channels and so, for extra processing the current amplification is necessary. It is notable that there are some problems in traditional electronic amplifier due to its noise and bandwidth problem. Because of the important role of the patch-clamp current in cancer research and especially its small amplitude, it is vital to intensify it without adding any noises. In this study, the current amplification is performed firstly: from the excitement of nanoparticles by the patch-clamp pico-ampere current and then, the effect of nanoparticles plasmonic far-field radiation on conductor's carriers, which will cause the current amplification. This relates to the plasmonic-photonic coupling and their effect on conductor carriers as the current perturbation agent. In the steady state, the current amplification can reach to 1000 times of initial level. Furthermore, we investigated the nanoparticles morphology changing effect such as size, nanoparticles inter-distance, and nanoparticles distance from the conductor on the amplifier parameters. Finally, it should note that the original aim is to use nanoparticles plasmonic engineering and their coupling to photonics for output current manipulating. PMID- 27676382 TI - Biosynthesis of silver nanoparticles using aqueous extract of silky hairs of corn and investigation of its antibacterial and anticandidal synergistic activity and antioxidant potential. AB - This paper investigated the green synthesis of silver nanoparticles (AgNPs) using aqueous extract of silky hairs of corn (Zea mays L.) which is a waste material of the crop, as both a reducing and stabilising/capping agent. The AgNPs were characterised by UV-visible spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The average size of AgNPs was found to be 249.12 nm. The AgNPs displayed strong antibacterial activity against five different foodborne pathogenic bacteria with diameter of inhibition zones ranged between (9.23 - 12.81 mm). It also exhibited potent synergistic antibacterial activity together with standard antibiotics, kanamycin (10.6 - 13.65 mm inhibition zones) and rifampicin (10.02 - 12.86 mm inhibition zones) and anticandidal activity with amphotericin b (10.57 - 13.63 mm inhibition zones). The AgNPs exhibited strong antioxidant activity in terms of nitric oxide scavenging (IC50 91.56 ug/mL), ABTS (2,2'-azino-bis(3 ethylbenzothiazoline-6-sulphonic acid) radical scavenging (IC50 115.75 ug/mL), DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging (IC50 385.87 ug/mL), and reducing power (IC0.5 23.14 ug/mL). This study demonstrated the synthesis of spherical AgNPs with strong antibacterial, anticandidal and antioxidant properties that could potentially be utilised in the biomedical, cosmetic, food and pharmaceutical industries. PMID- 27676381 TI - Catalytic degradation of methylene blue by biosynthesised copper nanoflowers using F. benghalensis leaf extract. AB - This study reports the unprecedented, novel and eco-friendly method for the synthesis of three-dimensional (3D) copper nanostructure having flower like morphology using leaf extract of Ficus benghalensis. The catalytic activity of copper nanoflowers (CuNFs) was investigated against methylene blue (MB) used as a modal dye pollutant. Scanning electron micrograph evidently designated 3D appearance of nanoflowers within a size range from 250 nm to 2.5 MUm. Energy dispersive X-ray spectra showed the presence of copper elements in the nanoflowers. Fourier-transform infrared spectra clearly demonstrated the presence of biomolecules which is responsible for the synthesis of CuNFs. The catalytic activity of the synthesised CuNFs was monitored by ultraviolet-visible spectroscopy. The MB was degraded by 72% in 85 min on addition of CuNFs and the rate constant (k) was found to be 0.77 * 10-3 s-1. This method adapted for synthesis of CuNFs offers a valuable contribution in the area of nanomaterial synthesis and in water research by suggesting a sustainable and an alternative route for removal of toxic solvents and waste materials. PMID- 27676383 TI - Anisotropic nanomechanical properties of bovine horn using modulus mapping. AB - Bovine horns are durable that they can withstand an extreme loading force which with special structures and mechanical properties. In this study, the authors apply quasi-static nanoindentation and modulus mapping techniques to research the nanomechanical properties of bovine horn in the transverse direction (TD) and longitudinal direction (LD). In quasi-static nanoindentation, the horn's modulus and hardness in the inner layer and the outer layer demonstrated a gradual increase in both TD and LD. Laser scanning confocal microscopy revealed microstructure in the horn with wavy morphology in the TD cross-section and laminate in the LD cross-section. When using tensile tests or quasi-static nanoindentation tests alone, the anisotropy of the mechanical properties of bovine horn were not obvious. However, when using modulus mapping, storage modulus (E'), loss modulus (E") and loss ratio (tan delta) are clearly different depending on the position in the TD and LD. Modulus mapping is proposed as accurately describing the internal structures of bovine horn and helpful in understanding the horn's energy-absorption, stiffness and strength that resists forces during fighting. PMID- 27676384 TI - Evaluation of the wound healing efficacy of chemical and phytogenic silver nanoparticles. AB - Wound healing requires a series of cellular events and a cascade of co-ordinated and systemic biochemical events. Silver nanoparticles possess many beneficial properties for wound management including antibacterial, anti-inflammatory and pro-healing properties. In this study, the authors investigated the wound healing properties of Cinnamomum verum extract mediated nanosilver (CENS) particles in comparison with 1% povidone iodine, citrate mediate NS and CE treatments. The topical application of CENS showed good antibacterial activity and accelerated wound healing with complete epithelialisation and normal re-growth of hair in all three models of study: namely, excision, incision and dead space models in rats compared with all other treatments. CENS was also found to promote collagen synthesis, stabilise wound besides countering oxidative stress and stimulating cellular proliferation CENS could be a novel therapeutic agent for wound management. PMID- 27676385 TI - Biofabrication of broad range antibacterial and antibiofilm silver nanoparticles. AB - Silver nanoparticles (AgNPs) were biosynthesized via a green route using ten different plants extracts (GNP1- Caryota urens, GNP2-Pongamia glabra, GNP3- Hamelia patens, GNP4-Thevetia peruviana, GNP5-Calendula officinalis, GNP6-Tectona grandis, GNP7-Ficus petiolaris, GNP8- Ficus busking, GNP9- Juniper communis, GNP10-Bauhinia purpurea). AgNPs were tested against drug resistant microbes and their biofilms. These nanoparticles (NPs) were characterised using UV-vis spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction and Image J software. Most of the AgNPs were distributed over a range of 1 of 60 nm size. The results indicated that AgNPs were antibacterial in nature without differentiating between resistant or susceptible strains. Moreover, the effect was more prominent on Gram negative bacteria then Gram positive bacteria and fungus. AgNPs inhibited various classes of microbes with different concentration. It was also evident from the results that the origin or nature of extract did not affect the activity of the NPs. Protein and carbohydrate leakage assays confirmed that the cells lysis is one of the main mechanisms for the killing of microbes by green AgNPs. This study suggests that the action of AgNPs on microbial cells resulted into cell lysis and DNA damage. Excellent microbial biofilm inhibition was also seen by these green AgNPs. AgNPs have proved their candidature as a potential antibacterial and antibiofilm agent against MDR microbes. PMID- 27676386 TI - Tenofovir Pre-exposure Prophylaxis for Pregnant and Breastfeeding Women at Risk of HIV Infection: The Time is Now. AB - In this Perspective, Lynne Mofenson discusses the implications of Mugwanya and colleagues' findings for protection of women against HIV infection during breastfeeding. PMID- 27676388 TI - Fate of sulfamethoxazole in groundwater: Conceptualizing and modeling metabolite formation under different redox conditions. AB - Degradation of emerging organic compounds in saturated porous media is usually postulated as following simple low-order models. This is a strongly oversimplified, and in some cases plainly incorrect model, that does not consider the fate of the different metabolites. Furthermore, it does not account for the reversibility in the reaction observed in a few emerging organic compounds, where the parent is recovered from the metabolite. One such compound is the antibiotic sulfamethoxazole (SMX). In this paper, we first compile existing experimental data to formulate a complete model for the degradation of SMX in aquifers subject to varying redox conditions, ranging from aerobic to iron reducing. SMX degrades reversibly or irreversibly to a number of metabolites that are specific of the redox state. Reactions are in all cases biologically mediated. We then propose a mathematical model that reproduces the full fate of dissolved SMX subject to anaerobic conditions and that can be used as a first step in emerging compound degradation modeling efforts. The model presented is tested against the results of the batch experiments of Barbieri et al. (2012) and Nodler et al. (2012) displaying a non-monotonic concentration of SMX as a function of time under denitrification conditions, as well as those of Mohatt et al. (2011), under iron reducing conditions. PMID- 27676387 TI - Using Bayesian hierarchical models to better understand nitrate sources and sinks in agricultural watersheds. AB - Export coefficient models (ECMs) are often used to predict nutrient sources and sinks in watersheds because ECMs can flexibly incorporate processes and have minimal data requirements. However, ECMs do not quantify uncertainties in model structure, parameters, or predictions; nor do they account for spatial and temporal variability in land characteristics, weather, and management practices. We applied Bayesian hierarchical methods to address these problems in ECMs used to predict nitrate concentration in streams. We compared four model formulations, a basic ECM and three models with additional terms to represent competing hypotheses about the sources of error in ECMs and about spatial and temporal variability of coefficients: an ADditive Error Model (ADEM), a SpatioTemporal Parameter Model (STPM), and a Dynamic Parameter Model (DPM). The DPM incorporates a first-order random walk to represent spatial correlation among parameters and a dynamic linear model to accommodate temporal correlation. We tested the modeling approach in a proof of concept using watershed characteristics and nitrate export measurements from watersheds in the Coastal Plain physiographic province of the Chesapeake Bay drainage. Among the four models, the DPM was the best--it had the lowest mean error, explained the most variability (R2 = 0.99), had the narrowest prediction intervals, and provided the most effective tradeoff between fit complexity (its deviance information criterion, DIC, was 45.6 units lower than any other model, indicating overwhelming support for the DPM). The superiority of the DPM supports its underlying hypothesis that the main source of error in ECMs is their failure to account for parameter variability rather than structural error. Analysis of the fitted DPM coefficients for cropland export and instream retention revealed some of the factors controlling nitrate concentration: cropland nitrate exports were positively related to stream flow and watershed average slope, while instream nitrate retention was positively correlated with nitrate concentration. By quantifying spatial and temporal variability in sources and sinks, the DPM provides new information to better target management actions to the most effective times and places. Given the wide use of ECMs as research and management tools, our approach can be broadly applied in other watersheds and to other materials. PMID- 27676389 TI - Untangling Heavy Protein and Cofactor Isotope Effects on Enzyme-Catalyzed Hydride Transfer. AB - "Heavy" (isotopically labeled) enzyme isotope effects offer a direct experimental probe of the role of protein vibrations on enzyme-catalyzed reactions. Here we have developed a strategy to generate isotopologues of the flavoenzyme pentaerythritol tetranitrate reductase (PETNR) where the protein and/or intrinsic flavin mononucleotide (FMN) cofactor are isotopically labeled with 2H, 15N, and 13C. Both the protein and cofactor contribute to the enzyme isotope effect on the reductive hydride transfer reaction, but their contributions are not additive and may partially cancel each other out. However, the isotope effect specifically arising from the FMN suggests that vibrations local to the active site play a role in the hydride transfer chemistry, while the protein-only "heavy enzyme" effect demonstrates that protein vibrations contribute to catalysis in PETNR. In all cases, enthalpy-entropy compensation plays a major role in minimizing the magnitude of "heavy enzyme" isotope effects. Fluorescence lifetime measurements of the intrinsic flavin mononucleotide show marked differences between "light" and "heavy" enzymes on the nanosecond-picosecond time scale, suggesting relevant time scale(s) for those vibrations implicated in the "heavy enzyme" isotope effect on the PETNR reaction. PMID- 27676390 TI - Long-Term Moderate Oxidative Stress Decreased Ovarian Reproductive Function by Reducing Follicle Quality and Progesterone Production. AB - Ovarian aging is a long-term and complex process associated with a decrease in follicular quantity and quality. The damaging effects of reactive oxygen species (ROS) in ovarian aging and ovarian aging-associated disorders have received relatively little attention. Thus, we assessed if the oxidative stress induced by long-term (defined by the Environmental Protection Agency as at least 30 days in duration) moderate ozone inhalation reduced ovarian reserves, decreased ovarian function and induced ovarian aging-associated disorders. The expression of oxidative stress markers and antioxidant enzymes was used to determine the degree of oxidative stress. Ultrastructural changes in ovarian cells were examined via electron microscopy. The ovarian reserve was assessed by measuring multiple parameters, such as the size of the primordial follicle pool and anti-Mullerian hormone (AMH) expression. The estrous cycle, hormone levels and fertility status were investigated to assess ovarian function. To investigate ovarian aging associated disorders, we utilized bone density and cardiovascular ultrasonography in mice. The levels of oxidized metabolites, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and nitrotyrosine (NTY), significantly increased in ovarian cells in response to increased oxidative stress. The ultrastructural analysis indicated that lipid droplet formation and the proportion of mitochondria with damaged membranes in granulosa cells were markedly increased in ozone-exposed mice when compared with the control group. Ozone exposure did not change the size of the primordial follicle pool or anti Mullerian hormone (AMH) expression. The estrogen concentration remained normal; however, progesterone and testosterone levels decreased. The mice exposed to ozone inhalation exhibited a substantial decrease in fertility and fecundity. No differences were revealed by the bone density or cardiovascular ultrasounds. These findings suggest that the decreased female reproductive function caused by long-term moderate oxidative damage may be due to a decrease in follicle quality and progesterone production. PMID- 27676392 TI - Metal Flux Growth, Structural Relations, and Physical Properties of EuCu2Ge2 and Eu3T2In9 (T = Cu and Ag). AB - Single crystals (SCs) of the compounds Eu3Ag2In9 and EuCu2Ge2 were synthesized through the reactions run in liquid indium. Eu3Ag2In9 crystallizes in the La3Al11 structure type [orthorhombic space group (SG) Immm] with the lattice parameters: a = 4.8370(1) A, b = 10.6078(3) A, and c = 13.9195(4) A. EuCu2Ge2 crystallizes in the tetragonal ThCr2Si2 structure type (SG I4/mmm) with the lattice parameters: a = b = 4.2218(1) A, and c = 10.3394(5) A. The crystal structure of Eu3Ag2In9 is comprised of edge-shared hexagonal rings consisting of indium. The one dimensional chains of In6 rings are shared through the edges, which are further interconnected with other six-membered rings forming a three-dimensional (3D) stable crystal structure along the bc plane. The crystal structure of EuCu2Ge2 can be explained as the complex [CuGe](2+delta)- polyanionic network embedded with Eu ions. These polyanionic networks present in the crystal structure of EuCu2Ge2 are shared through the edges of the 011 plane containing Cu and Ge atoms, resulting in a 3D network. The structural relationship between Eu3T2In9 and EuCu2Ge2 has been discussed in detail, and we conclude that Eu3T2In9 is the metal deficient variant of EuCu2Ge2. The magnetic susceptibilities of Eu3T2In9 (T = Cu and Ag) and EuCu2Ge2 were measured between 2 and 300 K. In all cases, magnetic susceptibility data followed Curie-Weiss law above 150 K. Magnetic moment values obtained from the measurements indicate the probable mixed/intermediate valent behavior of the europium atoms, which was further confirmed by X-ray absorption studies and bond distances around the Eu atoms. Electrical resistivity measurements suggest that Eu3T2In9 and EuCu2Ge2 are metallic in nature. PMID- 27676391 TI - The Role of Neutrophil Proteins on the Amyloid Beta-RAGE Axis. AB - We previously showed an elevated expression of the neutrophil protein, cationic antimicrobial protein of 37kDa (CAP37), in brains of patients with Alzheimer's disease (AD), suggesting that CAP37 could be involved in AD pathogenesis. The first step in determining how CAP37 might contribute to AD pathogenesis was to identify the receptor through which it induces cell responses. To identify a putative receptor, we performed GAMMA analysis to determine genes that positively correlated with CAP37 in terms of expression. Positive correlations with ligands for the receptor for advanced glycation end products (RAGE) were observed. Additionally, CAP37 expression positively correlated with two other neutrophil proteins, neutrophil elastase and cathepsin G. Enzyme-linked immunosorbent assays (ELISAs) demonstrated an interaction between CAP37, neutrophil elastase, and cathepsin G with RAGE. Amyloid beta 1-42 (Abeta1-42), a known RAGE ligand, accumulates in AD brains and interacts with RAGE, contributing to Abeta1-42 neurotoxicity. We questioned whether the binding of CAP37, neutrophil elastase and/or cathepsin G to RAGE could interfere with Abeta1-42 binding to RAGE. Using ELISAs, we determined that CAP37 and neutrophil elastase inhibited binding of Abeta1-42 to RAGE, and this effect was reversed by protease inhibitors in the case of neutrophil elastase. Since neutrophil elastase and cathepsin G have enzymatic activity, mass spectrometry was performed to determine the proteolytic activity of all three neutrophil proteins on Abeta1-42. All three neutrophil proteins bound to Abeta1-42 with different affinities and cleaved Abeta1-42 with different kinetics and substrate specificities. We posit that these neutrophil proteins could modulate neurotoxicity in AD by cleaving Abeta1-42 and influencing the Abeta1-42 -RAGE interaction. Further studies will be required to determine the biological significance of these effects and their relevance in neurodegenerative diseases such as AD. Our findings identify a novel area of study that underscores the importance of neutrophils and neutrophil proteins in neuroinflammatory diseases such as AD. PMID- 27676393 TI - Nudging Our Way to a Healthier Population: The Effect of Calorie Labeling and Self-Control on Menu Choices of Emerging Adults. AB - Emerging adults are among those in the United States with concerning rates of overweight and obesity, putting them at risk for chronic diseases. One proposed intervention to address these issues across populations is to require that chain restaurants and similar establishments provide nutrition information, such as calorie labels, on menu items. This study therefore aims to examine the effect of menu calorie labeling and self-control on food and beverage choices of emerging adults. Results of a between-subjects experiment (n = 179) revealed that calorie labeling increased the likelihood of choosing lower calorie food and beverage options. Moreover, calorie labeling only led to selecting a lower calorie food option among those with high self-control, but not among those with low self control. This moderating effect was not revealed for beverage choice. Public health practitioners and policymakers should consider intervention approaches that address other drivers of choice, such as self-control, in addition to nutrition information. PMID- 27676394 TI - Autoimmune Diseases in Children and Adults With Type 1 Diabetes From the T1D Exchange Clinic Registry. AB - BACKGROUND AND AIMS: Type 1 diabetes (T1D) is associated with other autoimmune diseases (AIDs), but the prevalence and associated predictive factors for these comorbidities of T1D across all age groups have not been fully characterized. MATERIALS AND METHODS: Data obtained from 25 759 participants with T1D enrolled in the T1D Exchange Registry were used to analyze the types and frequency of AIDs as well as their relationships to gender, age, and race/ethnicity. Diagnoses of autoimmune diseases, represented as ordinal categories (0, 1, 2, 3, or more AIDs) were obtained from medical records of Exchange Registry participants. RESULTS: Among the 25 759 T1D Exchange participants, 50% were female, 82% non-Hispanic white, mean age was 23.0 +/- 16.9 years and mean duration of diabetes was 11 years. Of these participants, 6876 (27%) were diagnosed with at least one AID. Frequency of two or more AIDs increased from 4.3% in participants aged younger than 13 years to 10.4% in those aged 50 years or older. The most common AIDs were thyroid (6097, 24%), gastrointestinal (1530, 6%), and collagen vascular diseases (432, 2%). Addison's disease was rare (75, 0.3%). The prevalence of one or more AIDs was increased in females and non-Hispanic whites and with older age. CONCLUSIONS: In the T1D Exchange Clinic Registry, a diagnosis of one or more AIDs in addition to T1D is common, particularly in women, non-Hispanic whites, and older individuals. Results of this study have implications for both primary care and endocrine practice and will allow clinicians to better anticipate and manage the additional AIDs that develop in patients with T1D. PMID- 27676395 TI - Urinary Citrate, an Index of Acid-Base Status, Predicts Bone Strength in Youths and Fracture Risk in Adult Females. AB - CONTEXT: Diet can impact on bone strength via metabolic shifts in acid-base status. In contrast to the strongly diet-dependent biomarker urinary potential renal acid load (uPRAL), the amount of renally excreted citrate integrates nutritional and systemic influences on acid-base homeostasis with high citrate indicating prevailing alkalization. OBJECTIVE: To examine the association between urinary citrate excretion and bone strength as well as long-term fracture risk. DESIGN AND PARTICIPANTS: Prospective cross-sectional analysis; 231 healthy children (6-18 y) of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study were included, with at least 2 urine collections available during the 4 years preceding peripheral quantitative computed tomography (pQCT) of the nondominant proximal forearm. uPRAL, urinary citrate, and urinary nitrogen excretion were quantified in 857 24-hour urine samples. Data on overall fracture incidence were collected within a 15-year follow-up after pQCT measurement. MAIN OUTCOME MEASURES: Parameters of bone quality and geometry (pQCT) as well as long term fracture incidence. RESULTS: After controlling for confounders, especially forearm length, muscle area, and urinary nitrogen (biomarker of protein intake), urinary citrate excretion was positively associated with various parameters of bone quality and geometry (P < .05). Fracture risk in adult females, but not in males, was inversely associated with urinary citrate and positively with uPRAL (P < .05). CONCLUSIONS: Although urinary citrate has to be confirmed as an integrated noninvasive biomarker of systemic acid-base status in further studies, our results substantiate dietary and metabolic acidity as potentially adverse for bone health in the long run from childhood onward. PMID- 27676396 TI - Healthy Subjects Differentially Respond to Dietary Capsaicin Correlating with Specific Gut Enterotypes. AB - CONTEXT: Previous population studies in evaluating the beneficial effects of capsaicin (CAP) have yielded inconclusive results, and the mechanisms responsible for possible benefit remain unclear. OBJECTIVE: The objective was to assess the effect of dietary CAP on metabolic and immune profiles and its potential associations with gut microbial patterns in healthy adults. DESIGN: In a 6-week controlled feeding trial, subjects were given the weight maintenance diet sequentially contained with 0, 5, 0, and 10 mg/d CAP from chili powder. SETTING AND PARTICIPANTS: The study was conducted in 12 healthy subjects enrolled in Third Military Medical University in Chongqing. MAIN OUTCOME MEASURES: At the end of each period, anthropometric and basal metabolism measures together with blood and fecal samples were collected. Plasma metabolic and inflammatory markers and gut microbial ecology of each subject were subsequently assessed. RESULT: Dietary CAP increased the Firmicutes/Bacteroidetes ratio and Faecalibacterium abundance, accompanied with increased plasma levels of glucagon-like peptide 1 and gastric inhibitory polypeptide and decreased plasma ghrelin level. Further enterotype analysis revealed that these subjects could be clustered into Bacteroides enterotype (E1) and Prevotella enterotype (E2), and the above beneficial effects were mainly obtained in E1 subjects. Moreover, E1 subjects had significantly higher fecal Faecalibacterium abundance and butyrate concentration after CAP interventions than those in E2 subjects. CONCLUSION: Our study showed that gut enterotypes may influence the beneficial effects of dietary CAP, providing new evidence for the personalized nutrition guidance of CAP intervention on health promotion linking with gut microbiota patterns. PMID- 27676397 TI - Impact of Parity on Body Size Phenotype in Postmenopausal Women: KNHANES 2010 2012. AB - CONTEXT: Parity has been implicated in many health consequences for women in later life. OBJECTIVE: To determine whether there is an association between parity and body size phenotypes in postmenopausal women. DESIGN AND PARTICIPANTS: This study was based on data from the Korean National Health and Nutrition Examination Survey, conducted during 2010-2012. Of the 25 534 participants, data from 3347 postmenopausal women were included in the analysis. RESULTS: In analyses stratified by the metabolically abnormal obese (MAO) and metabolically healthy and normal weight phenotypes, women with parities of 3-4 births or more than or equal to 5 births were significantly associated with the MAO phenotype (odds ratio [OR] 1.396 [95% confidence interval (CI) 1.077-1.810] and OR 1.978 [1.392-2.811], respectively) compared with those with a parity of 1-2 births after adjusting for age, sociodemographic factors, lifestyle behaviors, and reproductive factors. A similar significant association of parity with the MAO phenotype was also found when we analyzed the parity number as a continuous variable in a comparison of the MAO and metabolically abnormal but normal weight phenotypes (OR 1.116 [1.012-1.232]). In grouping of the MAO and metabolically healthy but obese phenotypes, women who had experienced a parity of 3-4 births or more than or equal to 5 births were significantly associated with the MAO phenotype (OR 1.459 [1.025-2.076] and OR 1.989 [1.211-3.265], respectively) after adjustment for the above covariates. CONCLUSIONS: Parity influenced the body size phenotype in postmenopausal women, and higher parity was independently associated with a higher risk of the MAO phenotype in postmenopausal women. PMID- 27676399 TI - XXIInd Congress of the European Society for Stereotactic and Functional Neurosurgery. Madrid, Spain,September 28-October 1, 2016: Abstracts. PMID- 27676398 TI - The Relationship Between Calciotropic Hormones, IGF-1, and Bone Mass Across Pubertal Stages. AB - BACKGROUND: Little is known about the changes in calciotropic hormones during puberty and their relationship to bone mass during this critical period for skeletal accretion. OBJECTIVES: Investigate changes in calciotropic hormones, IGF 1, body composition, and their associations with bone metabolism in adolescents. METHODS: Post hoc analyses were performed from data on 335 healthy school children, ages 10-17 years, with hypovitaminosis D who participated in a vitamin D randomized controlled trial. Baseline serum biochemistries; hormonal studies; densitometry at the spine, hip, and total body; and body composition were used. ANOVA and regression analyses were implemented to evaluate changes in variables of interest across pubertal stages, within and between genders. RESULTS: Bone mass and body composition parameters increased substantially across Tanner stages in both genders. Serum calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels did not vary by Tanner stages in both genders. Conversely, serum phosphorus, alkaline phosphatase, IGF-1, PTH, and osteocalcin peaked for the most part at Tanner stage II in girls and stage III in boys. 1,25-Dihydroxyvitamin D correlations with bone mass were not consistent, whereas IGF-1 was the most robust correlate of bone mass at several skeletal sites in early Tanner stages in both genders (R = 0.3-0.6). CONCLUSION: Serum phosphorus, alkaline phosphatase, IGF-1, PTH, and osteocalcin, but not calcium or 1,25-dihydroxyvitamin D, increased significantly in early puberty, with gender difference except for PTH, peaking earlier in girls than in boys. IGF-1 is a robust predictor of bone mass, an effect mediated in large part by increments in lean mass. PMID- 27676401 TI - Real-World Data: Responses to Zito and Doshi. PMID- 27676400 TI - Multiplex Competition, Collaboration, and Funding Networks Among Health and Social Organizations: Toward Organization-based HIV Interventions for Young Men Who Have Sex With Men. AB - BACKGROUND: Young men who have sex with men (YMSM) have the highest rates of human immunodeficiency virus (HIV) infection in the United States. Decades into the HIV epidemic, the relationships that YMSM-serving health and social organizations have with one another has not been studied in depth. OBJECTIVES: The aim of this study was to examine the competition, collaboration, and funding source structures of multiplex organization networks and the mechanisms that promote fruitful relationships among these organizations. RESEARCH DESIGN: The study data collection method was a survey of health and social organizations from 2013-2014 in 2 cities, Chicago, IL and Houston, TX. SUBJECTS: Study participants were representatives from 138 health and social organizations. MEASURES: Responses to survey questions were used to reconstruct competition, collaboration, and combined competition-collaboration networks. RESULTS: While taking into consideration the collaborative relationships among organizations, we provide statistical evidence that organizations of similar type, similar social media use patterns, comparable patterns of funding, and similar network contexts tended to compete with one another. This competition was less likely to be accompanied by any sort of collaboration if the organizations shared common funding sources. CONCLUSIONS: Competition that excludes potential collaboration may be detrimental to mobilizing the collective efforts that serve local YMSM communities. System-level interventions may provide promising approaches to scaling-up HIV prevention and treatment efforts so as to encourage organizations to form partnerships with otherwise competing providers. PMID- 27676402 TI - Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population. AB - BACKGROUND: The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Leri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. METHODS: We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. RESULTS: Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 +/- 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. CONCLUSIONS: Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions. PMID- 27676403 TI - Neuropilin-1 Is an Important Niche Component and Exerts Context-Dependent Effects on Hematopoietic Stem Cells. AB - Marrow adipocytes pose a significant problem in post-transplant regeneration of hematopoiesis owing to their negative effects on regeneration of hematopoiesis. However, the precise mechanism operative in this negative regulation is not clear. In this study, we show that marrow adipocytes express neuropilin-1 (NRP1) as a function of differentiation and inhibit regeneration of hematopoiesis by three principal mechanisms: one, by inducing apoptosis in hematopoietic stem/progenitor cells (HSPCs) through the death receptor-mediated pathway; two, by downregulating CXCR4 expression on the HSPCs through ligand-mediated internalization; and three, by secreting copious amounts of transforming growth factor beta1 (TGFbeta1), a known inhibitor of hematopoiesis. Silencing of NRP1 in these adipocytes rescued the apoptosis of cocultured HSPCs and boosted the CXCR4 surface expression on them, showing an active role of NRP1 in these processes. However, such silencing had no effect on TGFbeta1 secretion and consequent inhibition of hematopoiesis by them, showing that secretion of TGFbeta1 by adipocytes is independent of NRP1 expression by them. Surprisingly, mesenchymal stromal cells modified with NRP1 supported expansion of HSPCs having enhanced functionality, suggesting that NRP1 exerts a context-dependent effect on hematopoiesis. Our data demonstrate that NRP1 is an important niche component and exerts context-dependent effects on HSPCs. Based on these data, we speculate that antibody- or peptide-mediated blocking of NRP1-HSC interactions coupled with a pharmacological inhibition of TGFbeta1 signaling may help in combating the negative regulation of post-transplant regeneration of hematopoiesis in a more effective manner. PMID- 27676404 TI - RICTOR polymorphisms affect efficiency of platinum-based chemotherapy in Chinese non-small-cell lung cancer patients. AB - AIM: We investigated the association between RICTOR polymorphisms and clinical outcomes of platinum-based chemotherapy for Chinese non-small-cell lung cancer patients. MATERIALS & METHODS: Ten tag SNPs were genotyped in 1004 patients to assess their association with clinical benefit, overall survival, progression free survival, gastrointestinal toxicity, neutropenia, anemia and thrombocytopenia. RESULTS: rs6878291 was significantly associated with clinical benefit (odds ratio: 2.037; p = 0.001) and reduced progression-free survival (hazard ratio: 1.461; p = 0.001). Stratified analysis showed that their most significant interaction was in nonsmokers. No association was observed between SNPs and other clinical outcomes. CONCLUSION: The study showed evidences for RICTOR polymorphisms' role in platinum-based chemotherapy efficiency, which could provide new insight to lung cancer management. PMID- 27676405 TI - Update on emergency contraception. AB - PURPOSE OF REVIEW: Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years. RECENT FINDINGS: Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers. SUMMARY: Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception. PMID- 27676406 TI - Investigating Neovascularization in Rat Decellularized Intestine: An In Vitro Platform for Studying Angiogenesis. AB - One of the main challenges currently faced by tissue engineers is the loss of tissues postimplantation due to delayed neovascularization. Several strategies are under investigation to create vascularized tissue, but none have yet overcome this problem. In this study, we produced a decellularized natural vascular scaffold from rat intestine to use as an in vitro platform for neovascularization studies for tissue-engineered constructs. Decellularization resulted in almost complete (97%) removal of nuclei and DNA, while collagen, glycosaminoglycan, and laminin content were preserved. Decellularization did, however, result in the loss of elastin and fibronectin. Some proangiogenic factors were retained, as fragments of decellularized intestine were able to stimulate angiogenesis in the chick chorioallantoic membrane assay. We demonstrated that decellularization left perfusable vascular channels intact, and these could be repopulated with human dermal microvascular endothelial cells. Optimization of reendothelialization of the vascular channels showed that this was improved by continuous perfusion of the vasculature and further improved by infusion of human dermal fibroblasts into the intestinal lumen, from where they invaded into the decellularized tissue. Finally we explored the ability of the perfused cells to form new vessels. In the absence of exogenous angiogenic stimuli, Dll4, a marker of endothelial capillary tip cell activation during sprouting angiogenesis, was absent, indicating that the reformed vasculature was largely quiescent. However, after addition of vascular endothelial growth factor A, Dll4-positive endothelial cells could be detected, demonstrating that this engineered vascular construct maintained its capacity for neovascularization. In summary, we have demonstrated how a natural xenobiotic vasculature can be used as an in vitro model platform to study neovascularization and provide information on factors that are critical for efficient reendothelialization of decellularized tissue. PMID- 27676407 TI - Percutaneous Transcatheter Interventions for Aortic Insufficiency in Continuous Flow Left Ventricular Assist Device Patients: A Systematic Review and Meta Analysis. AB - De novo progressive aortic insufficiency (AI) is a side effect frequently related to prolonged support with continuous-flow left ventricular assist devices (CF LVAD). Its progression can result in recurrent clinical heart failure symptoms and significantly increased mortality. Recently, percutaneous intervention methods, such as transcatheter aortic valve replacement (TAVR) and percutaneous occluder devices, have emerged. However, given the very scarce global experience with these approaches, evidence in the literature is lacking. We sought to assess the outcomes of CF-LVAD patients who had undergone percutaneous intervention for AI. A systematic search of six databases from inception to April 2016 was performed by two independent reviewers. Eligible studies were those that included series or cases where patients had percutaneous transcatheter interventions for AI in CF-LVAD patients. Data were extracted and meta-analyzed from the identified studies. A total of 29 patients from 15 published studies and 3 unpublished records were included in the analysis. Mean patient age was 56.6 +/- 13.7 years, and 72.4% were male. The etiology of heart failure resulting in LVAD placement was ischemic cardiomyopathy in 17.2%. The two intervention groups were TAVR (27.6%) and occluder devices (72.4%). A transfemoral approach (69%), apical approach (10%), brachial approach (7%), subclavian approach (3%), and mini sternotomy (3%) were used. The preintervention AI grade was severe with a median grade of 4 (interquartile range, 4-4). Postoperatively, the AI grade improved significantly to a median grade of 0 (0-2). At long-term follow-up AI grade was still trivial with a median AI grade of 1 (0-1). Subgrouping the treatments into the occluder device and TAVR, it was found that both interventional techniques were similarly effective in reducing the AI grade from severe to trivial. In terms of complications, from the occluder group, two patients were complicated with device migration and another two with transient hemolysis. In the TAVR cohort, two patients experienced device migration and another had significant postimplant perivalvular leakage. Our results indicate that percutaneous interventions for AI in CF-LVAD patients with TAVR, and closure devices demonstrate similar efficacy in significantly reducing severe AI. Current results are encouraging, potentiating viability as a treatment option, particularly in nonsurgical candidates. Future research with larger patient cohorts and comparative controls is required to sufficiently evaluate the efficacy of this technique and promote its widespread acceptance as a mainstay treatment. PMID- 27676409 TI - Time in Therapeutic Range for Left Ventricular Assist Device Patients Anticoagulated With Warfarin: A Correlation to Clinical Outcomes. AB - Left ventricular assist devices (LVADs) require anticoagulation therapy with vitamin K antagonists to reduce the risk of thrombotic events. The quality of anticoagulation may be assessed by the time in therapeutic range (TTR). We analyzed a retrospective cohort of LVAD patients at a single institution from January 2012 to September 2014. Primary outcomes included TTR during the study time period and TTR 30 days preceding a bleeding or thrombotic event. Fifty-one patients (mean age 57.0 +/- 14.6 years; 78% male) had an overall TTR of 52%. Median international normalized ratio (INR) preceding a bleeding and thrombotic event was 2.7 and 2.2, respectively (p = 0.049). In the 30 days before an event, patients with a bleeding event were more likely to be on low-dose aspirin (37% vs. 12%; p = 0.018) and spend a higher proportion of time above therapeutic range (41% vs. 17%; p = 0.007) compared with those with thrombotic events. The association between a greater percentage of time above therapeutic range in the 30 days before a bleeding event demonstrates the importance of avoiding a supratherapeutic INR in the LVAD patient population and the usefulness of TTR as a measure of the overall quality of anticoagulation and monitoring in an LVAD cohort. PMID- 27676410 TI - Left Atrial Pressure Monitoring With an Implantable Wireless Pressure Sensor After Implantation of a Left Ventricular Assist Device. AB - After implantation of a continuous-flow left ventricular assist device (LVAD), left atrial pressure (LAP) monitoring allows for the precise management of intravascular volume, inotropic therapy, and pump speed. In this case series of 4 LVAD recipients, we report the first clinical use of this wireless pressure sensor for the long-term monitoring of LAP during LVAD support. A wireless microelectromechanical system pressure sensor (Titan, ISS Inc., Ypsilanti, MI) was placed in the left atrium in four patients at the time of LVAD implantation. Titan sensor LAP was measured in all four patients on the intensive care unit and in three patients at home. Ramped speed tests were performed using LAP and echocardiography in three patients. The left ventricular end-diastolic diameter (cm), flow (L/min), power consumption (W), and blood pressure (mm Hg) were measured at each step. Measurements were performed over 36, 84, 137, and 180 days, respectively. The three discharged patients had equipment at home and were able to perform daily recordings. There were significant correlations between sensor pressure and pump speed, LV and LA size and pulmonary capillary wedge pressure, respectively (r = 0.92-0.99, p < 0.05). There was no device failure, and there were no adverse consequences of its use. PMID- 27676411 TI - Short-Term Experience with Off-Pump Versus On-Pump Implantation of the HeartWare Left Ventricular Assist Device. AB - Implantation of left ventricular assist devices while avoiding cardiopulmonary bypass (CPB) may decrease bleeding and improve postoperative recovery. To understand the effectiveness of this approach, we reviewed the charts of 26 patients who underwent HeartWare left ventricular assist device (HVAD) implantation without use of CPB (off-CPB group) and 22 patients who had HVAD implanted with CPB (CPB group) with an emphasis on the 30 day postoperative period. Preoperatively, both groups had similar demographic, functional, and hemodynamic characteristics. Off-CPB patients had significantly shorter surgery times than CPB patients, 188.5 (161.5-213.3) min versus 265.0 (247.5-299.5) min, respectively; p < 0.001. Blood transfusion requirements during surgery and within the postoperative 48 hour period were significantly lower in the off-CPB group than in the CPB group (odds ratio: 5.9; 95% confidence interval: 1.1-31.1, p = 0.042). Compared with the CPB group, the off-CPB group patients had a shorter intubation time, 21 (17.4-48.5) hours versus 41 (20.6-258.4) hours; p = 0.042. Intensive care unit stay was 7.0 (4.75-13.5) days for off-CPB versus 10.0 (6.0 19.0) days for CPB (p = 0.256). The off-CPB approach allows HVAD to be implanted quickly with significantly less perioperative bleeding and transfusion requirements and facilitates postoperative rehabilitation. PMID- 27676412 TI - Predictors of Mortality in Long-Term Follow-Up of Patients with Terminal Alcoholic Cirrhosis: Is It Time to Accept Remodeled Scores? AB - OBJECTIVE: To identify the prognostic score that is the best predictor of outcome in patients hospitalized with decompensated liver cirrhosis. MATERIAL AND METHODS: In this prospective study, 126 patients were enrolled and followed up for 29 months. For each patient, prognostic scores were calculated; these included the Child-Turcotte-Pugh score (CTP score), CTP creatinine-modified I score, CTP creatinine-modified II score, Model for End-Stage Liver Disease (MELD score), MELD model for end-stage liver disease sodium-modified score, Integrated MELD score, updated MELD score, United Kingdom MELD, and the MELD score remodeled by serum sodium index (MESO index). Cox regression analysis was used to assess the ability of each of the scores for predicting mortality in patients with alcoholic cirrhosis. Their discriminatory ability was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The updated MELD score had the highest predictive value (3.29) among the tested scores (95% CI: 2.26 4.78). ROC curve analysis demonstrated that the MELD score of 22.50 (AUC = 0.914, 95% CI: 0.849-0.978; p < 0.001) had the best discriminative ability for identifying patients with a high risk of mortality; the next best was the MESO index of 16.00 (AUC = 0.912, 95% CI: 0.847-0.978; p < 0.001). CONCLUSION: The risk of mortality was highest in patients with the highest updated MELD score, and those with MELD scores >22.50 and a MESO index >16.00. PMID- 27676413 TI - First Report of Sex Chromosomes in Achiridae (Teleostei: Pleuronectiformes) with Inferences About the Origin of the Multiple X1X1X2X2/X1X2Y System and Dispersal of Ribosomal Genes in Achirus achirus. AB - American soles (family Achiridae) have been characterized by remarkable chromosomal variation even though several species lack basic cytogenetic information. This trend indicates that chromosomal traits can be useful to taxonomy once the morphological identification of some taxa in this family (e.g., Achirus species) is controversial. In this work, we expand the cytogenetic data in Achiridae by providing the first karyotypic analysis of Achirus achirus. An unusual multiple sex chromosome system (X1X1X2X2/X1X2Y) was detected, once males presented 2n = 33 with three unpaired chromosomes (X1X2Y) while females presented 2n = 34 with two acrocentric pairs (X1X1 and X2X2) found in hemizygosis in males. The 18S rDNA clusters were observed interspersed with GC-rich sites in a single pair. However, the 5S rRNA genes were dispersed through the genome of A. achirus in a sex-specific manner (10 clusters in males and 12 in females), as a result of the presence of ribosomal cistrons in X1 and X2 chromosomes. This pattern allowed us to infer that Y chromosome has evolved by partial deletion followed by fusion of proto-X1 and proto-X2 homologous chromosomes. The high rate of genomic evolution in Achiridae could have favored their reproductive isolation and speciation even in sympatric conditions. PMID- 27676414 TI - LMA SupremeTM and Ambu(r) AuraGainTM in anesthetized adult patients: a prospective observational study. AB - BACKGROUND: Second-generation laryngeal masks with gastric access are increasingly used in daily practice and expand the indications for laryngeal masks in the OR. Only limited data exist comparing different types of laryngeal masks. We investigated the second-generation laryngeal masks LMA SupremeTM and Ambu(r) AuraGainTM in a clinical setting. We hypothesized that the two devices would be comparable in terms of success rate and airway complications. METHODS: After approval from the local ethics committee, data were collected in a prospective trial. Endpoints were success rate, time to insertion and airway morbidity. Anesthesiologists used either the Supreme (Teleflex Medical GmbH) or Gain (Ambu GmbH) laryngeal mask. Patients <18 years and those with a possible risk of regurgitation were excluded. RESULTS: Data from 351 adult patients were documented (Supreme N.=177; Gain N.=174). Success rate for first attempt was 80% (Supreme) and 72% (Gain; P=0.08). Overall success rate was 89% and 92%, respectively (P=0.38). Providers with minimal experience were more successful at first attempt using Supreme (95%), compared to Gain (67%; P=0.01). The median insertion time was shorter in Supreme at 18 s [interquartile range (IQR), 14-25 s] compared to 30 s for Gain [18-41s] (P<0.0001). A higher incidence of airway complications was observed after device removal for Gain (P=0.009). CONCLUSIONS: Supreme was superior to Gain in terms of insertion time and airway morbidity. Novices were more successful at first attempt using Supreme. These differences between supraglottic airway devices might be due to the different shapes and materials of the masks. PMID- 27676415 TI - Impact of the post-anesthetic care unit opening hours on fast-track success in cardiac surgery. AB - BACKGROUND: Fast-track (FT) treatment in cardiac anesthesia is a state-of-the-art technique. The aim of our study was to compare FT treatment in a post-anesthetic care unit (PACU) with limited opening hours with a PACU opened for unlimited hours. Primary endpoints were extubation time (ET), length of stay (LOS) in PACU and LOS in intermediate care unit (IMC). Secondary endpoints were FT success/failure, hospital LOS, re-intubation and in hospital mortality. METHODS: At our institution, FT is usually managed in a PACU with limited opening hours from 10 a.m. to 10 p.m., Monday to Friday (PACU12). Due to reconstruction work in 2011, this PACU was open 24 hours a day, Monday to Saturday (PACU24). We retrospectively compared patients admitted to PACU24 during 2011 (January to December) and patients admitted to PACU12 during 2013 (January to December). RESULTS: A total of 2174 patients were primarily included in the study, 319 of them had to be excluded. Primary endpoints in PACU12 compared to PACU24 were significantly shorter: median ET (2.0 [95% confidence interval: 1.4-2.8] vs. 3.3 [95% CI: 2.2-5.0] hours), median LOS in PACU (4.8 [95% CI: 4.0-5.9] vs. 21.2 [95% CI: 18.3-23.5] hours) and median LOS in IMC (24 [95% CI: 18-64] vs. 38 [95% CI: 22-77] hours). FT success was significantly higher in PACU12 compared to PACU24 (75.3% vs. 39.6%). The in-hospital mortality and re-intubation rate were not significantly different. CONCLUSIONS: FT treatment in a PACU with limited opening hours leads to more effective treatment for patients regarding extubation time and LOS in IMC than in a PACU with limited opening hours, without compromising safety. PMID- 27676416 TI - The use of ultrasound guidance in intrathecal pump refill. PMID- 27676417 TI - Sugammadex dosing based on ideal or actual body weight: an open dilemma. PMID- 27676418 TI - Lack of matrix metalloproteinase 3 in mouse models of lung injury ameliorates the pulmonary inflammatory response in female but not in male mice. AB - BACKGROUND: The acute respiratory distress syndrome (ARDS) is a complex pulmonary disorder in which the local release of cytokines and chemokines appears central to the pathophysiology. OBJECTIVE: Based on the known role of matrix metalloproteinase-3 (MMP3) in inflammatory processes, the objective was to examine the role of MMP3 in the pathogenesis of ARDS through the modulation of pulmonary inflammation. MATERIALS AND METHODS: Female and male, wild type (MMP3+/+) and knock out (MMP3-/-) mice were exposed to two, clinically relevant models of ARDS including (i) lipopolysaccharide (LPS)-induced lung injury, and (ii) hydrochloric acid-induced lung injury. Parameters of lung injury and inflammation were assessed through measurements in lung lavage including total protein content, inflammatory cell influx, and concentrations of mediators such as TNF-alpha, IL-6, G-CSF, CXCL1, CXCL2, and CCL2. Lung histology and compliance were also evaluated in the LPS model of injury. RESULTS: Following intra-tracheal LPS instillation, all mice developed lung injury, as measured by an increase in lavage neutrophils, and decrease in lung compliance, with no overall effect of genotype observed. Increased concentrations of lavage inflammatory cytokines and chemokines were also observed following LPS injury, however, LPS-instilled female MMP3-/- mice had lower levels of inflammatory mediators compared to LPS-instilled female MMP3+/+ mice. This effect of the genotype was not observed in male mice. Similar findings, including the MMP3-related sex differences, were also observed after acid-induced lung injury. CONCLUSION: MMP3 contributes to the pathogenesis of ARDS, by affecting the pulmonary inflammatory response in female mice in relevant models of lung injury. PMID- 27676419 TI - Simultaneous determination of mycophenolate and its metabolite mycophenolate-7-o glucuronide with an isocratic HPLC-UV-based method in human plasma and stability evaluation. AB - OBJECTIVES: Mycophenolic acid (MPA) is an immunosuppressive agent which is commonly used in a fixed dose regime in solid organ transplantation. For clinical trials and therapeutic drug monitoring measuring plasma concentrations is necessary. Also, stability issues have to be addressed. METHODS: We describe an isocratic, RP-based HPLC-UV method for simultaneous determination of MPA and its major metabolite Mycophenolic acid 7-o Glucuronide (MPAG) in human plasma. Pre analytics included protein precipitation with acetonitrile. The method was validated according to EMA/FDA guidelines. Patient lithium-heparin plasma and blood was used for evaluation of short-term (72 hours at room temperature = RT) and long-term stability (2 years at -80 degrees C) without acidification. RESULTS: Linearity was assessed in the concentration range of 0.5-40.0 MUg/mL for MPA and 5.0-350.0 MUg/mL for MPAG, respectively. For MPA coefficient of variation was <7.0% (lower limit of quantification = LLOQ: 10.8%), for MPAG <9.6% (LLOQ: 10.6%). Bias ranged between -1.9 and +1.5% for MPA and for MPAG between -4.3 and 0.3%. The method showed agreement with a reference method for both analytes. MPA remained stable for 7 h (-1.6 to +8.4% change to the initial concentration) and MPAG for 24 h (-1.8 to -11.5% change) at RT in lithium heparin blood. After 2 years of storage at -80 degrees C MPA, MPAG concentrations and 95% CIs remained within +/-15% of the initial value. CONCLUSION: The presented assay is applicable for clinical studies. Blood samples were stable for 7 hours at RT and plasma for 2 years stored at -80 degrees C. PMID- 27676420 TI - A 52-Week Study of Olanzapine with a Randomized Behavioral Weight Counseling Intervention in Adolescents with Schizophrenia or Bipolar I Disorder. AB - OBJECTIVES: To evaluate the 52-week safety/tolerability of oral olanzapine for adolescents with schizophrenia or bipolar mania and compare effectiveness of a standard versus intense behavioral weight intervention in mitigating risk of weight gain. METHODS: Patients 13-17 years old with schizophrenia (Brief Psychiatric Rating Scale for Children [BPRS-C] total score >30; item score >=3 for hallucinations, delusions, or peculiar fantasies) or bipolar I disorder (manic or mixed episode; Young Mania Rating Scale [YMRS] total score >=15) received open-label olanzapine (2.5-20 mg/day) and were randomized to standard (n = 102; a single weight counseling session) or intense (n = 101; weight counseling at each study visit) weight intervention. The primary outcome measure was mean change in body mass index (BMI) from baseline to 52 weeks using mixed-model repeated measures. Symptomatology was also assessed. RESULTS: No statistically significant differences between groups were observed in mean baseline-to-52-week change in BMI (standard: +3.6 kg/m2; intense: +2.8 kg/m2; p = 0.150) or weight (standard: +12.1 kg; intense: +9.6 kg; p = 0.148). Percentage of patients at endpoint who had gained >=15% of their baseline weight was 40% for the standard group and 31% for the intense group (p = 0.187). Safety/tolerability results were generally consistent with those of previous olanzapine studies in adolescents, with the most notable exception being the finding of a mean decrease in prolactin. On symptomatology measures, patients with schizophrenia had a mean baseline-to-52-week change in BPRS-C of -32.5 (standard deviation [SD] = 10.8), and patients with bipolar disorder had a mean change in YMRS of -16.7 (SD = 8.9), with clinically and statistically significant improvement starting at 3-4 days for each. CONCLUSIONS: Long-term weight gain was high in both groups, with no statistically significant differences between the standard or intense behavioral weight interventions in BMI or weight. Safety, tolerability, and effectiveness findings were generally consistent with the known profile of olanzapine in adolescents. PMID- 27676421 TI - Myc is also the bad guy in myeloma. PMID- 27676422 TI - Optimizing treatment for nasal NK T-cell lymphoma. PMID- 27676423 TI - Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study. AB - BACKGROUND: Critical illness is hallmarked by low circulating thyroxine (T4) and triiodothyronine (T3) concentrations, in the presence of elevated reverse T3 (rT3) and low-normal thyrotropin (TSH), referred to as nonthyroidal illness (NTI). Thyroid hormone (TH) metabolism is substantially increased during NTI, in part explained by enhanced deiodinase 3 (D3) activity. T4- and T3-sulfate concentrations are elevated, due to suppressed D1 activity in the presence of unaltered sulfotransferase activity, and 3,3'-diiodothyronine (3,3'-T2) concentrations are normal. To elucidate further the driving forces behind increased TH metabolism during NTI, two other potential T4 metabolites-3,5 diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM)-were measured and related to their potential TH precursors. METHODS: Morning blood samples were collected cross-sectionally from 83 critically ill patients on a University Hospital intensive care unit and from 38 demographically matched healthy volunteers. Serum TH and binding proteins were quantified with commercial assays, and 3,5-T2 and 3 T1AM with in-house developed immunoassays. RESULTS: Critically ill patients revealed, besides the NTI, a median 44% lower serum 3-T1AM concentration (p < 0.0001) and a 30% higher serum 3,5-T2 concentration (p = 0.01) than healthy volunteers did. Non-survivors and patients diagnosed with sepsis upon admission to the intensive-care unit had significantly higher 3,5-T2 (p <= 0.01) but comparable 3-T1AM (p > 0.2) concentrations than other patients did. Multivariable linear regression analysis adjusted for potential precursors revealed that the reduced serum 3-T1AM was positively correlated with the low serum T3 (p < 0.001) but unrelated to serum T4 or rT3. The elevated 3,5-T2 concentration did not independently correlate with TH. CONCLUSIONS: Increased TH metabolism during NTI could not be explained by increased conversion to 3-T1AM, as circulating 3-T1AM was suppressed in proportion to the concomitantly low T3 concentrations. Increased conversion of T4 and/or T3 to 3,5-T2 could be possible, as serum 3,5-T2 concentrations were elevated. Whether 3-T1AM or 3,5-T2 plays a functional role during critical illness needs further investigation. PMID- 27676425 TI - New Perspectives, 15 Years On. PMID- 27676424 TI - Diverse profiles of N-acyl-homoserine lactones in biofilm forming isolates of Cronobacter sakazakii. PMID- 27676426 TI - The Maturation of Development. AB - An updated, broader definition of developmental biology is needed to capture the full range of exciting research directions of the field, as current studies of adult homeostasis and physiology are extending developmental biology's "Golden Age." PMID- 27676427 TI - The Actin Cortex: A Bridge between Cell Shape and Function. AB - The cortical actin network controls many animal cell shape changes by locally modulating cortical tension. Recent work has provided insight into cortex components and regulators. However, how the network is reorganized in response to cellular signaling, and the role reorganization may play during cell state changes, remain to be determined. PMID- 27676428 TI - Single-Cell Approaches: Pandora's Box of Developmental Mechanisms. AB - Single-cell approaches are providing a new lexicon of developmental cell biology by revealing heterogeneities in seemingly uniform cellular populations. By bridging scales, single-cell approaches should, in principle, galvanize our understanding of how individual cells adopt distinct fates as they build complex tissues. PMID- 27676429 TI - Resolving Conflicts: Modeling Genetic Control of Plant Morphogenesis. AB - Computational modeling of tissue morphogenesis reveals how spatiotemporal patterns of gene activity control tissue shape by introducing several types of tissue conflict. These conflicts reflect genetic modulation of processes that influence the cellular mechanical properties and may underlie the enormous diversity of forms that have evolved in plants and animals. PMID- 27676430 TI - Cell Division in the Light of Modeling. AB - Theoretical modeling is central to elucidating underlying principles of emergent properties of complex systems. In cell and developmental biology, the last 15 years have witnessed a convergence of empirical and modeling approaches for fresh perspectives. The role of cell division in coordinating size, shape, and fate in particular illustrates the ever-growing impact of modeling. PMID- 27676431 TI - Bottom-Up Biology: Harnessing Engineering to Understand Nature. AB - Engineering as a field has fundamentally different goals than biology, but the perspective that engineers take-that systems can be designed and built-is helping to advance biological sciences by motivating and equipping efforts to construct biological systems from the bottom up. PMID- 27676432 TI - Organoids: Modeling Development and the Stem Cell Niche in a Dish. AB - Organoids are three-dimensional in-vitro-grown cell clusters with near-native microanatomy that arise from self-organizing mammalian pluripotent or adult stem cells. Although monolayer stem cell cultures were established more than 40 years ago, organoid technology has recently emerged as an essential tool for both fundamental and biomedical research. For developmental biologists, organoids provide powerful means for ex vivo modeling of tissue morphogenesis and organogenesis. Here we discuss how organoid cultures of the intestine and other tissues have been established and how they are utilized as an in vitro model system for stem cell research and developmental biology. PMID- 27676433 TI - Engineered Microenvironments to Direct Epidermal Stem Cell Behavior at Single Cell Resolution. AB - Mammalian epidermis is maintained through proliferation of stem cells and differentiation of their progeny. The balance between self-renewal and differentiation is controlled by a variety of interacting intrinsic and extrinsic factors. Although the nature of these interactions is complex, they can be modeled in a reductionist fashion by capturing single epidermal stem cells on micropatterned substrates and exposing them to individual stimuli, alone or in combination, over defined time points. These studies have shown that different extrinsic stimuli trigger a common outcome-initiation of terminal differentiation by activating different signaling pathways and eliciting different transcriptional responses. PMID- 27676434 TI - Chromatin Control of Developmental Dynamics and Plasticity. AB - Chromatin structure is intimately connected with gene expression and cell identity. Here we review recent advances in the field and discuss how establishment of cell identity during development is accompanied by large-scale remodeling of the epigenetic landscape and how this remodeling drives and supports lineage specification and maintenance. We discuss maternal control of the early embryonic epigenetic landscape, selective usage of enhancer clusters via 3D chromatin contacts leading to activation of transcription factor networks, and conserved regulation of developmental pathways by specific DNA demethylation of key regulatory regions. Together, these processes establish an epigenetic framework regulating different phases of embryonic development. PMID- 27676435 TI - Cell Competition and Its Role in the Regulation of Cell Fitness from Development to Cancer. AB - Cell competition is a cell fitness-sensing mechanism conserved from insects to mammals that eliminates those cells that, although viable, are less fit than their neighbors. An important implication of cell competition is that cellular fitness is not only a cell-intrinsic property but is also determined relative to the fitness of neighboring cells: a cell that is of suboptimal fitness in one context may be "super-fit" in the context of a different cell population. Here we discuss the mechanisms by which cell competition measures and communicates cell fitness levels and the implications of this mechanism for development, regeneration, and tumor progression. PMID- 27676437 TI - Generating Cellular Diversity and Spatial Form: Wnt Signaling and the Evolution of Multicellular Animals. AB - There were multiple prerequisites to the evolution of multicellular animal life, including the generation of multiple cell fates ("cellular diversity") and their patterned spatial arrangement ("spatial form"). Wnt proteins operate as primordial symmetry-breaking signals. By virtue of their short-range nature and their capacity to activate both lineage-specifying and cell-polarizing intracellular signaling cascades, Wnts can polarize cells at their site of contact, orienting the axis of cell division while simultaneously programming daughter cells to adopt diverging fates in a spatially stereotyped way. By coupling cell fate to position, symmetry-breaking Wnt signals were pivotal in constructing the metazoan body by generating cellular diversity and spatial form. PMID- 27676436 TI - A Case for Distributed Control of Local Stem Cell Behavior in Plants. AB - The root meristem has a centrally located group of mitotically quiescent cells, to which current models assign a stem cell organizer function. However, evidence is emerging for decentralized control of stem cell activity, whereby self renewing behavior emerges from the lack of cell displacement at the border of opposing differentiation gradients. We term this a "stagnation" model due to its reliance on passive mechanics. The position of stem cells is established by two opposing axes that reciprocally control each other's differentiation. Such broad tissue organization programs would allow plants, like some animal systems, to rapidly reconstitute stem cells from non-stem-cell tissues. PMID- 27676438 TI - Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs. AB - Treatment of congenital heart defects in children requiring right ventricular outflow tract reconstruction typically involves multiple open-heart surgeries because all existing graft materials have no growth potential. Here we present an 'off-the-shelf' vascular graft grown from donor fibroblasts in a fibrin gel to address this critical unmet need. In a proof-of-concept study, the decellularized grafts are implanted as a pulmonary artery replacement in three young lambs and evaluated to adulthood. Longitudinal ultrasounds document dimensional growth of the grafts. The lambs show normal growth, increasing body weight by 366% and graft diameter and volume by 56% and 216%, respectively. Explanted grafts display physiological strength and stiffness, complete lumen endothelialization and extensive population by mature smooth muscle cells. The grafts also show substantial elastin deposition and a 465% increase in collagen content, without signs of calcification, aneurysm or stenosis. Collectively, our data support somatic growth of this completely biological graft. PMID- 27676439 TI - IL-22 binding protein regulates murine skin inflammation. PMID- 27676440 TI - Assessment of increased sampling pump flow rates in a disposable, inhalable aerosol sampler. AB - A newly designed, low-cost, disposable inhalable aerosol sampler was developed to assess workers personal exposure to inhalable particles. This sampler was originally designed to operate at 10 L/min to increase sample mass and, therefore, improve analytical detection limits for filter-based methods. Computational fluid dynamics modeling revealed that sampler performance (relative to aerosol inhalability criteria) would not differ substantially at sampler flows of 2 and 10 L/min. With this in mind, the newly designed inhalable aerosol sampler was tested in a wind tunnel, simultaneously, at flows of 2 and 10 L/min flow. A mannequin was equipped with 6 sampler/pump assemblies (three pumps operated at 2 L/min and three pumps at 10 L/min) inside a wind tunnel, operated at 0.2 m/s, which has been shown to be a typical indoor workplace wind speed. In separate tests, four different particle sizes were injected to determine if the sampler's performance with the new 10 L/min flow rate significantly differed to that at 2 L/min. A comparison between inhalable mass concentrations using a Wilcoxon signed rank test found no significant difference in the concentration of particles sampled at 10 and 2 L/min for all particle sizes tested. Our results suggest that this new aerosol sampler is a versatile tool that can improve exposure assessment capabilities for the practicing industrial hygienist by improving the limit of detection and allowing for shorting sampling times. PMID- 27676441 TI - Cerebral [18 F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy. AB - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr?1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects. PMID- 27676442 TI - Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A. AB - Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice. PMID- 27676444 TI - No effect of glucose administration in a novel contextual fear generalization protocol in rats. AB - The excessive transfer of fear acquired for one particular context to similar situations has been implicated in the development and maintenance of anxiety disorders, such as post-traumatic stress disorder. Recent evidence suggests that glucose ingestion improves the retention of context conditioning. It has been speculated that glucose might exert that effect by ameliorating hippocampal functioning, and may hold promise as a therapeutic add-on in traumatized patients because improved retention of contextual fear could help to restrict its generalization. However, direct data regarding the effect of glucose on contextual generalization are lacking. Here, we introduce a new behavioral protocol to study such contextual fear generalization in rats. In adult Wistar rats, our procedure yields a gradient of generalization, with progressively less freezing when going from the original training context, over a perceptually similar generalization context, to a markedly dissimilar context. Moreover, we find a flattening of the gradient when the training-test interval is prolonged with 1 week. We next examine the effect of systemic glucose administration on contextual generalization with this novel procedure. Our data do not sustain generalization-reducing effects of glucose and question its applicability in traumatic situations. In summary, we have developed a replicable contextual generalization procedure for rats and demonstrate how it is a valuable tool to examine the neurobiological correlates and test pharmacological interventions pertaining to an important mechanism in the etiology of pathological anxiety. PMID- 27676443 TI - Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid. AB - Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD. In the course of development, VPA-exposed rats showed early deficits in social communication and discrimination, compromised sociability and social play behavior, stereotypies and increased anxiety, thus providing preclinical proof of the long-lasting deleterious effects induced by prenatal VPA exposure. At the neurochemical level, VPA-exposed rats displayed altered phosphorylation of CB1 cannabinoid receptors in different brain areas, associated with changes in anandamide metabolism from infancy to adulthood. Interestingly, enhancing anandamide signaling through inhibition of its degradation rescued the behavioral deficits displayed by VPA-exposed rats at infancy, adolescence and adulthood. This study therefore shows that abnormalities in anandamide activity may underlie the deleterious impact of environmental risk factors on ASD-relevant behaviors and that the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients. PMID- 27676445 TI - Bottom-up proteomics suggests an association between differential expression of mitochondrial proteins and chronic fatigue syndrome. AB - Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest. An area of investigation is the likely connection of CFS with defective mitochondrial function. In a previous work, we investigated the proteomic salivary profile in a couple of monozygotic twins discordant for CFS. Following this work, we analyzed mitochondrial proteins in the same couple of twins. Nano-liquid chromatography electrospray ionization mass spectrometry (nano-LC-MS) was used to study the mitochondria extracted from platelets of the twins. Subsequently, we selected three proteins that were validated using western blot analysis in a big cohort of subjects (n=45 CFS; n=45 healthy), using whole saliva (WS). The selected proteins were as follows: aconitate hydratase (ACON), ATP synthase subunit beta (ATPB) and malate dehydrogenase (MDHM). Results for ATPB and ACON confirmed their upregulation in CFS. However, the MDHM alteration was not confirmed. Thereafter, seeing the great variability of clinical features of CFS patients, we decided to analyze the expression of our proteins after splitting patients according to clinical parameters. For each marker, the values were actually higher in the group of patients who had clinical features similar to the ill twin. In conclusion, these results suggest that our potential markers could be one of the criteria to be taken into account for helping in diagnosis. Furthermore, the identification of biomarkers present in particular subgroups of CFS patients may help in shedding light upon the complex entity of CFS. Moreover, it could help in developing tailored treatments. PMID- 27676446 TI - Endocannabinoid signaling in social functioning: an RDoC perspective. AB - Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited. Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning. Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning. This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors-Delta9 tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning. Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories. The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning. PMID- 27676448 TI - Introduction of the 2016 ASP Eminent Parasitologist Recipient. PMID- 27676447 TI - Supertetrahedral Networks and Lithium-Ion Mobility in Li2 SiP2 and LiSi2 P3. AB - The new phosphidosilicates Li2 SiP2 and LiSi2 P3 were synthesized by heating the elements at 1123 K and characterized by single-crystal X-ray diffraction. Li2 SiP2 (I41 /acd, Z=32, a=12.111(1) A, c=18.658(2) A) contains two interpenetrating diamond-like tetrahedral networks consisting of corner-sharing T2 supertetrahedra [(SiP4/2 )4 ]. Sphalerite-like interpenetrating networks of uniquely bridged T4 and T5 supertetrahedra make up the complex structure of LiSi2 P3 (I41 /a, Z=100, a=18.4757(3) A, c=35.0982(6) A). The lithium ions are located in the open spaces between the supertetrahedra and coordinated by four to six phosphorus atoms. Temperature-dependent 7 Li solid-state MAS NMR spectroscopic data indicate high mobility of the Li+ ions with low activation energies of 0.10 eV in Li2 SiP2 and 0.07 eV in LiSi2 P3 . PMID- 27676449 TI - Iron-Catalyzed, Fluoroamide-Directed C-H Fluorination. AB - This communication describes a mild, amide-directed fluorination of benzylic, allylic, and unactivated C-H bonds mediated by iron. Upon exposure to a catalytic amount of iron(II) triflate (Fe(OTf)2), N-fluoro-2-methylbenzamides undergo chemoselective fluorine transfer to provide the corresponding fluorides in high yield. The reaction demonstrates broad substrate scope and functional group tolerance without the use of any noble metal additives. Mechanistic and computational experiments suggest that the reaction proceeds through short-lived radical intermediates with F-transfer mediated directly by iron. PMID- 27676450 TI - Relief of Xylose Binding to Cellobiose Phosphorylase by a Single Distal Mutation. AB - Cellobiose phosphorylase (CBP) cleaves cellobiose-abundant in plant biomass-to glucose and glucose 1-phosphate. However, the pentose sugar xylose, also abundant in plant biomass, acts as a mixed-inhibitor and a substrate for the reverse reaction, limiting the industrial potential of CBP. Preventing xylose, which lacks only a single hydroxymethyl group relative to glucose, from binding to the CBP active site poses a spatial challenge for protein engineering, since simple steric occlusion cannot be used to block xylose binding without also preventing glucose binding. Using CRISPR-based chromosomal library selection, we identified a distal mutation in CBP, Y47H, responsible for improved cellobiose consumption in the presence of xylose. In silico analysis suggests this mutation may alter the conformation of the cellobiose phosphorylase dimer complex to reduce xylose binding to the active site. These results may aid in engineering carbohydrate phosphorylases for improved specificity in biofuel production, and also in the production of industrially important oligosaccharides. PMID- 27676451 TI - Poly(monothiocarbonate)s from the Alternating and Regioselective Copolymerization of Carbonyl Sulfide with Epoxides. AB - Carbonyl sulfide (COS) is an air pollutant that causes acid rain, ozonosphere damage, and carbon dioxide (CO2) generation. It is a heterocumulene and structural analogue of CO2. Relevant to organic synthesis, it is a source of C?O or C?S groups and thus an ideal one-carbon (C1) building block for synthesizing sulfur-containing polymers through the similar route of CO2 copolymerization. In contrast, traditional synthesis of sulfur-containing polymers often involves the condensation of thiols with phosgene and ring-opening polymerization of cyclic thiocarbonates that are generally derived from thiols and phosgene; thus, COS/epoxide copolymerization is a "greener" route to supplement or supplant current processes for the production of sulfur-containing polymers. This Accounts highlights our efforts on the discovery of the selective formation of poly(monothiocarbonate)s from COS with epoxides via heterogeneous zinc-cobalt double metal cyanide complex (Zn-Co(III) DMCC) and homogeneous (salen)CrX complexes. The catalytic activity and selectivity of Zn-Co(III) DMCC for COS/epoxide copolymerization are similar to those for CO2/epoxide copolymerization. (salen)CrX complexes accompanied by onium salts exhibited high activity and selectivity for COS/epoxide copolymerization under mild conditions, affording copolymers with >99% monothiocarbonate units and high tail-to-head content up to 99%. By way of contrast, these catalysts often show moderate or low activity for CO2/epoxide copolymerization. Of note, a specialty of COS/epoxide copolymerization is the occurrence of an oxygen-sulfur exchange reaction (O/S ER), which may produce carbonate and dithiocarbonate units. O/S ER, which are induced by the metal-OH bond regenerated by chain transfer reactions, can be kinetically inhibited by changing the reaction conditions. We provide a thorough mechanistic understanding of the electronic/steric effect of the catalysts on the regioselectivity of COS copolymerization. The regioselectivity of the copolymerization originates from the solely nucleophilic attack of the sulfur anion to methylene of the epoxide, and thus, the chiral configuration of the monosubstituted epoxides is retained. COS-based copolymers are highly transparent sulfur-containing polymers with excellent optical properties, such as high refractive index and Abbe number. Thanks to their good solubility and many available epoxides, COS/epoxide copolymers can potentially be a new applicable optical material. Very recently, crystalline COS-based polymers with or without chiral carbons have been synthesized, which may further expand the scope of application of these new materials. PMID- 27676453 TI - Big, Deep, and Smart Data in Scanning Probe Microscopy. AB - Scanning probe microscopy (SPM) techniques have opened the door to nanoscience and nanotechnology by enabling imaging and manipulation of the structure and functionality of matter at nanometer and atomic scales. Here, we analyze the scientific discovery process in SPM by following the information flow from the tip-surface junction, to knowledge adoption by the wider scientific community. We further discuss the challenges and opportunities offered by merging SPM with advanced data mining, visual analytics, and knowledge discovery technologies. PMID- 27676452 TI - Molecular modeling and redesign of alginate lyase from Pseudomonas aeruginosa for accelerating CRPA biofilm degradation. AB - Administration of an efficient alginate lyase (AlgL) or AlgL mutant may be a promising therapeutic strategy for treatment of cystic fibrosis patients with Pseudomonas aeruginosa infections. Nevertheless, the catalytic activity of wild type AlgL is not sufficiently high. It is highly desired to design and discover an AlgL mutant with significantly improved catalytic efficiency against alginate substrates. For the purpose of identifying an AlgL mutant with significantly improved catalytic activity, in this study, we first constructed and validated a structural model of AlgL interacting with substrate, providing a better understanding of the interactions between AlgL and its substrate. Based on the modeling insights, further enzyme redesign and experimental testing led to discovery of AlgL mutants, including the K197D/K321A mutant, with significantly improved catalytic activities against alginate and acetylated alginate in ciprofloxacin-resistant P. aeruginosa (CRPA) biofilms. Further anti-biofilm activity assays have confirmed that the K197D/K321A mutant with piperacillin/tazobactam is indeed effective in degrading the CRPA biofilms. Co administration of the potent mutant AlgL and an antibiotic (such as a nebulizer) could be effective for therapeutic treatment of CRPA-infected patients with cystic fibrosis. Proteins 2016; 84:1875-1887. (c) 2016 Wiley Periodicals, Inc. PMID- 27676454 TI - Challenging diagnostic issues in adenomatous polyps with epithelial misplacement in bowel cancer screening: 5 years' experience of the Bowel Cancer Screening Programme Expert Board. AB - The diagnostic difficulties of differentiating epithelial misplacement from invasive cancer in colorectal adenomatous polyps have been recognised for many years. Nevertheless, the introduction of population screening in the UK has resulted in extraordinary diagnostic problems. Larger sigmoid colonic adenomatous polyps, which are those most likely to show epithelial misplacement, are specifically selected into such screening programmes, because these polyps are likely to bleed and screening is based on the detection of occult blood. The diagnostic challenges associated with this particular phenomenon have necessitated the institution of an 'Expert Board': this is a review of the first five years of its practice, during which time 256 polyps from 249 patients have been assessed. Indeed, the Expert Board contains three pathologists, because those pathologists do not necessarily agree, and a consensus diagnosis is required to drive appropriate patient management. However, this study has shown substantial levels of agreement between the three Expert Board pathologists, whereby the ultimate diagnosis has been changed, from that of the original referral diagnosis, by the Expert Board for half of all the polyps, in the substantial majority from malignant to benign. In 3% of polyp cases, the Expert Board consensus has been the dual diagnosis of both epithelial misplacement and adenocarcinoma, further illustrating the diagnostic difficulties. The Expert Board of the Bowel Cancer Screening Programme in the UK represents a unique and successful development in response to an extraordinary diagnostic conundrum created by the particular characteristics of bowel cancer screening. PMID- 27676457 TI - Incorrect Spelling of Author Name in the Article by Brown et al (Arthritis Care Res [Hoboken] August, 2016). PMID- 27676458 TI - Translation and Validation of the Thai Version of a Modified Brief Pain Inventory: A Concise Instrument for Pain Assessment in Postoperative Cardiac Surgery. AB - BACKGROUND: Acute pain after cardiac surgery can be assessed using validated instruments such as the modified interference subscale of the Brief Pain Inventory (mod-BPI). Despite the available knowledge, the Thai version of a mod BPI has not yet been presented. OBJECTIVES: To translate a mod-BPI into the Thai language (BPI-T) and to validate it in acute pain after cardiac surgery. METHODS: This multisetting, cross-sectional study was done from 4 cardiac centers. With a convenience sampling technique, 132 cardiac surgery patients were enrolled during the first 72 postoperative hours. A BPI-T composed of 4 items on the intensity subscale and 6 items on the interference subscale was translated following Brislin's model. Convergent validity against the numeric rating scale (NRS), confirmatory factor analysis (CFA), and internal consistency reliability were examined. RESULTS: Of the total sample, 70% experienced moderate to severe pain (cutoff points of worst pain >= 4/10), and 65% had moderate to severe interference with deep breathing and coughing, 53% with general activity, and 49% with walking. The CFA confirmed the 2-factor structure of intensity and interference subscales consistent with the original version (root-mean-square error of approximation = 0.08, comparative fit index = 0.95, chi2 = 39.00, df = 27, chi2 /df = 1.44, P = 0.06). The physical and mental subdimensions under the interference subscale were determined (standardized factor loading = 0.70 and 0.42, respectively). The BPI-T also has good internal consistency (Cronbach's alpha coefficients 0.76 and 0.85). Pearson's correlation coefficients at 0.35 to 0.70 supported the convergent validity to the NRS. CONCLUSIONS: The BPI-T is a concise instrument for pain assessment in postoperative cardiac surgery. PMID- 27676459 TI - Scalable Production of Sensor Arrays Based on High-Mobility Hybrid Graphene Field Effect Transistors. AB - We have developed a scalable fabrication process for the production of DNA biosensors based on gold nanoparticle-decorated graphene field effect transistors (AuNP-Gr-FETs), where monodisperse AuNPs are created through physical vapor deposition followed by thermal annealing. The FETs are created in a four-probe configuration, using an optimized bilayer photolithography process that yields chemically clean devices, as confirmed by XPS and AFM, with high carrier mobility (3590 +/- 710 cm2/V.s) and low unintended doping (Dirac voltages of 9.4 +/- 2.7 V). The AuNP-Gr-FETs were readily functionalized with thiolated probe DNA to yield DNA biosensors with a detection limit of 1 nM and high specificity against noncomplementary DNA. Our work provides a pathway toward the scalable fabrication of high-performance AuNP-Gr-FET devices for label-free nucleic acid testing in a realistic clinical setting. PMID- 27676455 TI - Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation. AB - The impact of allograft injury time of onset on the risk of chronic lung allograft dysfunction (CLAD) remains unknown. We hypothesized that episodes of late-onset (>=6 months) allograft injury would produce an augmented CXCR3/ligand immune response, leading to increased CLAD. In a retrospective single-center study, 1894 transbronchial biopsy samples from 441 lung transplant recipients were reviewed for the presence of acute rejection (AR), lymphocytic bronchiolitis (LB), diffuse alveolar damage (DAD), and organizing pneumonia (OP). The association between the time of onset of each injury pattern and CLAD was assessed by using multivariable Cox models with time-dependent covariates. Bronchoalveolar lavage (BAL) CXCR3 ligand concentrations were compared between early- and late-onset injury patterns using linear mixed-effects models. Late onset DAD and OP were strongly associated with CLAD: adjusted hazard ratio 2.8 (95% confidence interval 1.5-5.3) and 2.0 (1.1-3.4), respectively. The early onset form of these injury patterns did not increase CLAD risk. Late-onset LB and acute rejection (AR) predicted CLAD in univariable models but lost significance after multivariable adjustment for late DAD and OP. AR was the only early-onset injury pattern associated with CLAD development. Elevated BAL CXCR3 ligand concentrations during late-onset allograft injury parallel the increase in CLAD risk and support our hypothesis that late allograft injuries result in a more profound CXCR3/ligand immune response. PMID- 27676456 TI - Induction of mucosal immune responses against Helicobacter pylori infection after sublingual and intragastric route of immunization. AB - There is a current lack of effective mucosal vaccines against major gastroenteric pathogens and particularly against Helicobacter pylori, which causes a chronic infection that can lead to peptic ulcers and gastric cancer in a subpopulation of infected individuals. Mucosal CD4+ T-cell responses have been shown to be essential for vaccine-induced protection against H. pylori infection. The current study addresses the influence of the adjuvant and site of mucosal immunization on early CD4+ T-cell priming to H. pylori antigens. The vaccine formulation consisted of H. pylori lysate antigens and mucosal adjuvants, cholera toxin (CT) or a detoxified double-mutant heat-labile enterotoxin from Escherichia coli (dmLT), which were administered by either the sublingual or intragastric route. We report that in vitro, adjuvants CT and dmLT induce up-regulation of pro inflammatory gene expression in purified dendritic cells and enhance the H. pylori-specific CD4+ T-cell response including interleukin-17A (IL-17A), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) secretion. In vivo, sublingual immunization led to an increased frequency of IL 17A+ , IFN-gamma+ and TNF-alpha+ secreting CD4+ T cells in the cervical lymph nodes compared with in the mesenteric lymph nodes after intragastric immunization. Subsequently, IL-17A+ cells were visualized in the stomach of sublingually immunized and challenged mice. In summary, our results suggest that addition of an adjuvant to the vaccine clearly activated dendritic cells, which in turn, enhanced CD4+ T-cell cytokines IL-17A, IFN-gamma and TNF-alpha responses, particularly in the cervical lymph nodes after sublingual vaccination. PMID- 27676460 TI - The impact of prior back surgery on neuromodulation outcomes: A review of over 500 patients. AB - AIMS: To evaluate neuromodulation outcomes in patients with prior back surgery. METHODS: Adults in our prospective observational sacral/pudendal neuromodulation study were retrospectively evaluated. History and operative details were reviewed, and outcomes were measured at 3, 6, 12, and 24 months with overactive bladder questionnaire (OAB q) symptom severity (SS)/health related quality of life (HRQOL), interstitial cystitis symptom/problem indices (ICSI - PI), voiding diaries, and global response assessments (GRA). Data were examined with Pearson's chi2 , Fisher's exact, Wilcoxon rank sum tests, and logistic regression multivariate analysis. RESULTS: Five hundred and sixty patients were evaluated (mean age 58.8 +/- 17 years; 83% female; 79% had a sacral lead placed), 109 (19%) had history of back surgery; 66 surgeries were lumbar. Back surgery patients were older (mean 63 +/- 15 vs. 58 +/- 17 years; P = 0.003) and a higher proportion had urge urinary incontinence (UUI) (64% vs. 50% P = 0.008). Generator implant rates were similar (94% vs. 91%; P = 0.34). OABq-SS and HRQOL and ICSI - PI composite scores did not differ between groups at any time point. On bladder diaries, median incontinence episodes daily at baseline and between stages were worse in the prior back surgery group but all bladder diary parameters improved significantly in both groups with the exception of mean voided volume which only improved significantly in the non-back surgery group. Most patients in both groups reported moderate/marked improvement in overall bladder symptoms. CONCLUSIONS: This study suggests that prior back surgery does not appear to impact clinical outcomes; therefore, neuromodulation may be offered in this patient population. PMID- 27676461 TI - Discovery of a Red-Emitting Li3RbGe8O18:Mn4+ Phosphor in the Alkali-Germanate System: Structural Determination and Electronic Calculations. AB - A solid-state combinatorial chemistry approach, which used the A-Ge-O (A = Li, K, Rb) system doped with a small amount of Mn4+ as an activator, was adopted in a search for novel red-emitting phosphors. The A site may have been composed of either a single alkali metal ion or of a combination of them. This approach led to the discovery of a novel phosphor in the above system with the chemical formula Li3RbGe8O18:Mn4+. The crystal structure of this novel phosphor was solved via direct methods, and subsequent Rietveld refinement revealed a trigonal structure in the P31m space group. The discovered phosphor is believed to be novel in the sense that neither the crystal structure nor the chemical formula matches any of the prototype structures available in the crystallographic information database (ICDD or ICSD). The measured photoluminescence intensity that peaked at a wavelength of 667 nm was found to be much higher than the best intensity obtained among all the existing A2Ge4O9 (A = Li, K, Rb) compounds in the alkali-germanate system. An ab initio calculation based on density function theory (DFT) was conducted to verify the crystal structure model and compare the calculated value of the optical band gap with the experimental results. The optical band gap obtained from diffuse reflectance measurement (5.26 eV) and DFT calculation (4.64 eV) results were in very good agreement. The emission wavelength of this phosphor that exists in the deep red region of the electromagnetic spectrum may be very useful for increasing the color gamut of LED based display devices such as ultrahigh-definition television (UHDTV) as per the ITU-R BT.2020-2 recommendations and also for down-converter phosphors that are used in solar-cell applications. PMID- 27676462 TI - Systematic Review of Postural Assessment in Individuals With Obstructive Respiratory Conditions: MEASUREMENT AND CLINICAL ASSOCIATIONS. AB - PURPOSE: Changes in posture in individuals with an obstructive respiratory disease have been reported, but the extent of these deviations and their clinical significance is not well understood. This study aimed to systematically review the literature of the skeletal structural alignment in children and adults with an obstructive respiratory disease, describe the measurement techniques used, and determine the clinical relevance of any alternations. METHODS: Observational cohort or cross-sectional studies of postural assessment were identified, with 2 reviewers independently assessing study quality. RESULTS: A total of 18 studies were included, 12 in cystic fibrosis (CF), 5 in asthma, and 1 in chronic obstructive pulmonary disease (COPD). The overall quality assessment rating was 12.6 out of 16. Increased thoracic kyphosis or scoliosis was found in both children and adults with CF. Increased shoulder protraction and elevation were evident in asthma and COPD, although changes in spinal curvature were variable. The clinical impact of postural changes was diverse, with an inconsistent influence on lung function. A mix of methods was applied for postural assessment. CONCLUSIONS: Skeletal structural malalignment appears to be present in some individuals with an obstructive respiratory disease, although the extent of alterations and its clinical impact is variable. Photogrammetry is used to provide a comprehensive assessment of posture in these populations. PMID- 27676463 TI - Impact of Home- and Hospital-Based Exercise in Cardiac Rehabilitation on Hopelessness in Patients With Coronary Heart Disease. AB - PURPOSE: Hopelessness is associated with increased adverse events and decreased survival in patients with coronary heart disease (CHD). The purpose of this research was to examine the effect of regular home- and hospital-based cardiac rehabilitation (CR) exercise on hopelessness levels in patients with CHD, hypothesizing that increased exercise in either setting would lead to decreased state hopelessness. METHODS: A descriptive longitudinal design was used at a large teaching hospital in Michigan. A total of 324 patients provided data during hospitalization and at least 1 followup time point (3, 8, and 12 months). RESULTS: The patients had persistent, modest levels of state and trait hopelessness across all time points. Among home exercisers with moderate to severe state hopelessness at baseline, both mean state (P = .002) and trait (P = .02) hopelessness were reduced at later time points compared with those who quit or did not start exercise. Multivariable models showed that when individuals had moderate to severe baseline state hopelessness, home exercise remained associated with decreases in state hopelessness compared with no exercise, even after adjusting for hospital exercise, depression, and demographic variables. CONCLUSIONS: Exercise may be effective in reducing moderate to severe hopelessness in patients with CHD. Moderate to severe baseline state hopelessness was a predictor of attrition in this cohort, especially for home exercisers, but this was mediated in hospital-based programs. Further research is needed to determine how hopeless individuals can be encouraged to exercise and whether home or a hospital-based CR exercise is superior in impacting hopelessness. PMID- 27676464 TI - Disparities in Cardiac Rehabilitation Participation in the United States: A SYSTEMATIC REVIEW AND META-ANALYSIS. AB - PURPOSE: Phase 2 cardiac rehabilitation (CR) is a class I recommendation for all patients following an acute cardiac event or cardiac surgery according to the The American Heart Association and the American College of Cardiology Foundation. Studies have shown that there are differences in cardiac rehabilitation participation rates between sociodemographic groups. The purpose of this systematic review and meta-analyses was to synthesize quantitative data on the relationship between outpatient cardiac rehabilitation (OCR) attendance and various sociodemographic factors. METHODS: We conducted a search of PubMed, PsycINFO, CINAHL, Google Scholar, Dissertations & Theses A&I, and conference abstracts for observational studies conducted in the United States that fit our inclusion criteria. A total of 21 studies were included in our final review and meta-analyses. RESULTS: Our meta-analyses showed that overall, attenders were younger than nonattenders (mean difference=-3.74 years, 95% CI =-5.87 to -1.61) and the odds of participation were lower among females (OR = 0.59; 95% CI = 0.51 0.69), individuals with a high school degree or less (OR = 0.67; 95% CI = 0.50 0.91), and the uninsured or self-payers (OR = 0.32; 95% CI = 0.14-0.71). Full- or part-time employees were more likely to participate than those not employed (OR = 1.45; 95% CI = 1.08-1.95). CONCLUSIONS: Our systematic review and meta-analyses showed that there are significant sociodemographic disparities in CR participation. On the basis of this knowledge, clinicians and policy makers should focus on identifying and eliminating barriers to participation. PMID- 27676465 TI - Association Between Phase 3 Cardiac Rehabilitation and Clinical Events. AB - PURPOSE: There is an inverse relationship between phase 2 cardiac rehabilitation (CR) visits and all-cause mortality. Phase 3 CR is a maintenance exercise program for which clinical outcomes are uncertain. This retrospective study describes the association between phase 3 CR participation and clinical events among patients with ischemic heart disease after completion of phase 2 CR. METHODS: Patients who completed 12 visits of phase 2 CR as provided by their health insurance were categorized on the basis of their frequency of participation (ie, none, irregular, and regular) in phase 3 CR during the 8 weeks after phase 2 CR. Cox regression analysis was used to evaluate the association between phase 3 CR participation and risk for a composite outcome that included all-cause mortality, nonfatal myocardial infarction, or heart failure hospitalization. RESULTS: Among 2039 patients (32% women; age = 59 +/- 10 years) who completed phase 2 CR, 101 were regular and 129 were irregular participants of phase 3 CR. Over a median followup of 5.6 years, 556 (27%) patients experienced the outcome. Neither irregular nor regular participation in phase 3 CR was significantly associated with risk for the outcome in unadjusted (P = .671 and P = .396, respectively) or adjusted (P = .737 and P = .890, respectively) analyses. CONCLUSIONS: We did not observe an incremental clinical benefit from weekly participation in Phase 3 CR after completion of phase 2 CR among patients with ischemic heart disease. Additional research addressing the dose-response relationship between phase 2 and 3 CR and clinical outcomes is needed. PMID- 27676467 TI - Developmental Assessment. PMID- 27676468 TI - Personal Vehicles Evaluated against Climate Change Mitigation Targets. AB - Meeting global climate change mitigation goals will likely require that transportation-related greenhouse gas emissions begin to decline within the next two decades and then continue to fall. A variety of vehicle technologies and fuels are commercially available to consumers today that can reduce the emissions of the transportation sector. Yet what are the best options, and do any suffice to meet climate policy targets? Here, we examine the costs and carbon intensities of 125 light-duty vehicle models on the U.S. market today and evaluate these models against U.S. emission-reduction targets for 2030, 2040, and 2050 that are compatible with the goal of limiting mean global temperature rise to 2 degrees C above preindustrial levels. Our results show that consumers are not required to pay more for a low-carbon-emitting vehicle. Across the diverse set of vehicle models and powertrain technologies examined, a clean vehicle is usually a low cost vehicle. Although the average carbon intensity of vehicles sold in 2014 exceeds the climate target for 2030 by more than 50%, we find that most hybrid and battery electric vehicles available today meet this target. By 2050, only electric vehicles supplied with almost completely carbon-free electric power are expected to meet climate-policy targets. PMID- 27676469 TI - Phenyltetrazolyl-phenylamides: Substituent impact on modulation capability and selectivity toward the efflux protein ABCG2 and investigation of interaction with the transporter. AB - We recently presented a novel class of ABCG2 modulators based on the third generation ABCB1 inhibitor tariquidar bearing a 2,5-linked tetrazole instead of an amid linker. We investigated the modulating potential of the compound class by enlarging the substitution pattern on the outer phenyl rings of the scaffold. To identify the structural conditions for achieving a high response, we decided to determine the individual influence of substituents on the scaffold using monosubstituted derivatives. While electron withdrawing groups (with a few exceptions) and bulky moieties decreased the modulating potency, small electron donating groups ensured a high activity level. Interestingly, the unsubstituted derivative 32 reached a similar inhibitory potential as the best derivatives in the previous study. Enzyme kinetic assays indicated that our derivatives have the same binding site as reference inhibitor Ko143. They were found to interact competitively and non-competitively with the substrates Hoechst 33342 and pheophorbide A, respectively. PMID- 27676470 TI - New isoxazolidinone and 3,4-dehydro-beta-proline derivatives as antibacterial agents and MAO-inhibitors: A complex balance between two activities. AB - Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, induces in many cases loss of selectivity as a major concern. A small library of compounds based on isoxazolidinone and dehydro-beta-proline scaffold was designed with the aim to obtain antibacterial agents, evaluating at the same time the potential effects of structural features on MAO inhibitory behaviour. The structural modification introduced in the backbone, starting from Linezolid model, lead to a significant loss in antibiotic activity, while a promising inhibitory effect could be observed on monoamino oxidases. These interesting results are also in agreement with docking experiments suggesting a good binding pose of the synthesized compounds into the pocket of the oxidase enzymes, in particular of MAO-B. PMID- 27676466 TI - Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study. AB - OBJECTIVES: To test whether average long-term glucose exposure is associated with cognitive and physical function in middle-aged and younger-old adults with type 2 diabetes mellitus. DESIGN: Prospective cohort study. SETTING: Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Movement and Memory ancillary study (NCT01410097). PARTICIPANTS: Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 at baseline (N = 879). MEASUREMENTS: Glycosylated hemoglobin (HbA1c) was measured at regular intervals over 7 years, and objective measures of cognitive function (Trail-Making Test, Modified Stroop Color-Word Test, Digit Symbol-Coding, Rey Auditory Verbal Learning Test, Modified Mini-Mental State Examination) and physical function (Short Physical Performance Battery, expanded Physical Performance Battery, 400-m and 20-m gait speed) and strength (grip and knee extensor strength) were assessed at the Year 8 or 9 follow-up examination. RESULTS: Average HbA1c exposure was 7.0 +/- 1.1% (53 +/- 11.6 mmol/mol), with 57% of participants classified as having HbA1c levels of less than 7% (<53 mmol/mol), 27% having levels of 7% to 8% (53-64 mmol/mol), and 16% having levels of greater than 8% (>64 mmol/mol). After adjustment for age, sex, race, education, smoking status, alcohol intake, knee pain, physical fitness, body mass index, diabetes mellitus medication and statin use, ancillary year visit, and study arm and site, higher HbA1c was associated with worse physical but not cognitive function. Further adjustment for prevalent diabetes mellitus-related comorbidities made all associations nonsignificant. Results did not differ when stratified according to participant baseline age (<60 vs >= 60). CONCLUSION: Results presented here suggest that, in the absence of diabetes mellitus-related complications, longitudinal glucose exposure is not associated with future cognitive and physical function. Optimal management of diabetes mellitus-related comorbidities may prevent or reduce the burden of disability associated with type 2 diabetes mellitus. PMID- 27676471 TI - Further investigation of Paprotrain: Towards the conception of selective and multi-targeted CNS kinase inhibitors. AB - Starting from a known compound, identified as the first inhibitor of the kinesin MKLP-2 and named Paprotrain, we have investigated its reactivity to produce through photochemistry a potent nanomolar inhibitor of the kinase DYRK1A. Using similar and different chemical pathways, we have designed several families of compounds that have been screened on a panel of five protein kinases: CK1delta/epsilon, CDK5/p25, GSK3alpha/beta, DYRK1A and CLK1, all involved in neurodegenerative disorders such as Alzheimer's disease. We have identified a first group of multi-targeted compounds, a second group of dual inhibitors of DYRK1A & CLK1 and a last group of selective inhibitors of CLK1. Then, our best submicromolar to nanomolar inhibitors were evaluated towards the closest members of the aforementioned kinases: DYRK1B and CLK4, as well as the subfamily CLK2-3. Several compounds appear to be particularly promising for the development of tools in the battle against Alzheimer's disease. PMID- 27676472 TI - O.02: Plasma Next Generation Sequencing of Over 5,000 Advanced Non-Small Cell Lung Cancer Patients With Clinical Correlations. PMID- 27676473 TI - O.01: Acquired Resistance to EGFR-TKIs in EGFR-Mutant Lung Adenocarcinoma Among Hispanics (RBIOP-CLICaP). PMID- 27676474 TI - O.03: Cost Effectiveness of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Relative to PD-L1 Expression. PMID- 27676475 TI - O.04: Profiling of MET-Amplified Non-Small Cell Lung Cancer (NSCLC), Correlation to cMET Protein Expression/MET Exon 14 Skipping. PMID- 27676477 TI - PD1.02 (also presented as P2.47): The Role of PD-L1 Expression as a Predictive Biomarker in Advanced NSCLC: An Update of a Network Meta-Analysis. PMID- 27676476 TI - PD1.01 (also presented as P2.46): LCSS as a Marker of Treatment Benefit With Nivolumab vs Docetaxel in Pts With Advanced Non-Squamous NSCLC From Checkmate 057. PMID- 27676478 TI - PD1.03 (also presented as P1.12): EGFR Mutation Testing Patterns and Results in Brazil and the Need for Greater Public Health Awareness of Molecular Testing. PMID- 27676479 TI - PD1.04 (also presented as P2.19): Infrequent Staining Patterns in ALK Immunohistochemistry: Correlation With Fish Analysis. PMID- 27676480 TI - PD1.06 (also presented as P2.41): Pembrolizumab vs Docetaxel for Previously Treated NSCLC (KEYNOTE-010): Archival vs New Tumor Samples for PD-L1 Assessment. PMID- 27676482 TI - PD2.01 (also presented as P1.13): Lung Cancer Chromosomal Aberrations and Gene Expression Profiles of Hispanics Living in the US or Latin America are Similar. PMID- 27676481 TI - PD1.05 (also presented as P1.49): The Genomics of Young Emergent Lung Cancer. PMID- 27676483 TI - PD2.02 (also presented as P1.44): Phase I/II Trial of X-396, a Novel ALK Inhibitor, in Patients With ALK+ NSCLC. PMID- 27676484 TI - PD2.04 (also presented as P1.42): PEM/CBP/BEV Followed by Maintenance PEM/BEV in Hispanic Patients With NSCLC: Outcomes According to TS, ERCC1 and VEGF. PMID- 27676485 TI - PD2.06 (also presented as P1.41): Bayesian Network Meta-Comparison of Maintenance Treatments for Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients. PMID- 27676486 TI - PD2.05 (also presented as P1.43): Radiosurgery, a New Paradigm in Metastatic Non Small Cell Lung Cancer (NSCLC) to the Brain: An Update. PMID- 27676487 TI - P1.02: Lung Cancer - A Previously Years Survival Study. First Statistical Evidence at National Institute of Oncology in Paraguay: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676488 TI - P1.01: Herbal Medicine Today: Clinical and Research Issues: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676489 TI - P1.03: Utility of a Combined Panel of Six Serum Tumor Markers for Lung Cancer: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676490 TI - P1.04: Defining the Genetic Architecture of Lung Cancer Etiology: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676491 TI - P1.05: An International Epidemiological Analysis of Young Patients Diagnosed With NSCLC (ADUJOV-CLICaP): Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676492 TI - P1.06: Lung Nodule Volumetry: Analysis of the Measurement Variation: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676493 TI - P1.08: Updated Analysis of Global Epidemiology of EGFR Mutation in Advanced Non Small Cell Lung Cancer: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676494 TI - P1.07: University Students' Perceptions About Effectiveness of Mpower Policies on Tobacco Control: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676495 TI - P1.10: Follow-Up on Results of a Multidisciplinary Team in the Management of Non Small Cell Lung Cancer in a Developing Country: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676496 TI - P1.09: Delays in the Diagnosis and Treatment of Lung Cancer: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676497 TI - P1.11: Surveillance System of Tabaquism in Cuba 1995-2014 and Early Detection in Heavy Smokers: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676498 TI - P1.13 (also presented as PD2.01): Lung Cancer Chromosomal Aberrations and Gene Expression Profiles of Hispanics Living in the US or Latin America are Similar: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676499 TI - P1.12 (also presented as PD1.03): EGFR Mutation Testing Patterns and Results in Brazil and the Need for Greater Public Health Awareness of Molecular Testing: Track: Prevention, Early Detection, Epidemiology and Tobacco Control. PMID- 27676500 TI - P1.14: Energy-Based Instruments for Pulmonary Artery Ligation in Thoracoscopic Major Lung Resection: Track: Early Stage NSCLC (Stage I - III). PMID- 27676501 TI - P1.15: Comparison of Pulmonary Function After Robotic-Assisted Video Thoracoscopic Lobectomies vs Segmentectomies: Track: Early Stage NSCLC (Stage I - III). PMID- 27676502 TI - P1.16: Comparison of Peri-Operative Outcomes After Robotic-Assisted Video Thoracoscopic Lobectomies Versus Segmentectomies: Track: Early Stage NSCLC (Stage I - III). PMID- 27676503 TI - P1.17: Improved Survival for Stage-2 (N1) Pulmonary Adenocarcinoma and Squamous Cell Carcinoma After Pulmonary Lobectomy: Track: Early Stage NSCLC (Stage I - III). PMID- 27676504 TI - P1.18: Long-Term Clinical Outcomes and Safety Profile for Central Lung SBRT for NSCLC: Track: Early Stage NSCLC (Stage I - III). PMID- 27676505 TI - P1.19: Barriers to Deliver Personalized Medicine to Young Patients With Non-Small Cell Lung Cancer in Latin America: Track: Early Stage NSCLC (Stage I - III). PMID- 27676506 TI - P1.20: Lung Resection Analysis From Brazilian Society of Thoracic Surgery Database: Track: Early Stage NSCLC (Stage I - III). PMID- 27676507 TI - P1.21: Novel PET Parameters as Predictors of Pathologic Response in Patients With Stage IIIA(N2) NSCLC Receiving Trimodality Therapy: Track: Early Stage NSCLC (Stage I - III). PMID- 27676508 TI - P1.22: Temporal Survival Improvement for Stage-II (T3N0M0) Lung Adenocarcinoma After Pulmonary Lobectomy: Track: Early Stage NSCLC (Stage I - III). PMID- 27676509 TI - P1.23: Chemotherapy in Lung Cancer at National Institute of Oncology at Paraguay: A Retrospective Study, 8 Years of Experience: Track: Advanced NSCLC. PMID- 27676510 TI - P1.24: 1st Line Treatment With Erlotinib in Advanced Non Squamous NSCLC: Our Experience. CCSS, San Jose Costa Rica: Track: Advanced NSCLC. PMID- 27676511 TI - P1.25: Experience With Erlotinib and Gefitnib in Patients With EGFR Mutation Positive Advanced Lung Cancer: Track: Advanced NSCLC. PMID- 27676512 TI - P1.26: A Case of Non Small Cell Lung Cancer EGFR Mutation EXON 18 Positive With Poor Response to Targeted Therapy: Track: Advanced NSCLC. PMID- 27676513 TI - P1.27: A Clinicopathological Study of Resected Pulmonary Pleomorphic Carcinoma: Track: Advanced NSCLC. PMID- 27676514 TI - P1.29: "Real World" Use of Liquid Biopsy in Patients With Lung Adenocarcinoma and Correlation With Tumor Tissue Genetic Profile: Track: Advanced NSCLC. PMID- 27676515 TI - P1.28: Overall Survival in Patients With Metastatic Lung Adenocarcinoma Treated at Instituto Oncologico Nacional. Panama: Track: Advanced NSCLC. PMID- 27676516 TI - P1.30: Clinical Efficacy and Tolerability of Bevacizumab in Elderly Patients With Advanced Non-Squamous NSCLC: Track: Advanced NSCLC. PMID- 27676517 TI - P1.31: Pleural Empyema and Broncho Pleural Fistula After Lung Resection: Analyses of 29 Patients Treated in our Clinic: Track: Advanced NSCLC. PMID- 27676518 TI - P1.32: Primary Lung Cancer Presenting as Pneumothorax: Track: Advanced NSCLC. PMID- 27676519 TI - P1.33: Afatinib Versus Chemotherapy for EGFR Mutation-Positive NSCLC Patients Aged >=65 Years: Subgroup Analysis of LUX-Lung 3/6: Track: Advanced NSCLC. PMID- 27676520 TI - P1.34: First-Line Afatinib vs Gefitinib for Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: The LUX-Lung 7 Trial: Track: Advanced NSCLC. PMID- 27676521 TI - P1.36: Non-Small-Cell Lung Cancer and Brain Metastases in Brazil: Track: Advanced NSCLC. PMID- 27676522 TI - P1.35: The Role of Salvage SBRT in Recurrent Lung Cancer After Previous Radiotherapy: Track: Advanced NSCLC. PMID- 27676523 TI - P1.37: First Line Treatment Outcome for EGFR Mutated Metastatic Non-Small Cell Lung Cancer-A Single Institution 5 Years Experience: Track: Advanced NSCLC. PMID- 27676524 TI - P1.38: Relationship Between TILs and Neutrophil-Lymphocyte Ratio as a Prognostic Factor in Advanced NSCLC: Track: Advanced NSCLC. PMID- 27676526 TI - P1.41 (also presented as PD2.06): Bayesian Network Meta-Comparison of Maintenance Treatments for Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients: Track: Advanced NSCLC. PMID- 27676525 TI - P1.39: Only Two Rare Metastasis of Lung Adenocarcinoma?: Track: Advanced NSCLC. PMID- 27676527 TI - P1.40: Comparative Study of Chemotherapy Regimens Based on Platinum and Its Different Toxicities in Patients With Advanced NSCLC: Track: Advanced NSCLC. PMID- 27676528 TI - P1.42 (also presented as PD2.04): PEM/CBP/BEV Followed by Maintenance PEM/BEV in Hispanic Patients With NSCLC: Outcomes According to TS, ERCC1 and VEGF: Track: Advanced NSCLC. PMID- 27676529 TI - P1.44 (also presented as PD2.02): Phase I/II Trial of X-396, A Novel ALK Inhibitor, in Patients With ALK+ NSCLC: Track: Advanced NSCLC. PMID- 27676530 TI - P1.43 (also presented as PD2.05): Radiosurgery, a New Paradigm in Metastatic Non Small Cell Lung Cancer (NSCLC) to the Brain: An Update: Track: Advanced NSCLC. PMID- 27676532 TI - P1.46: Phase I Study of Nivolumab + Nab-Paclitaxel in Solid Tumors: Preliminary Analysis of the Non-Small Cell Lung Cancer Cohort: Track: Advanced NSCLC. PMID- 27676531 TI - P1.45: Impact of Dose Adjustment on Afatinib Safety and Efficacy in EGFR Mutation Positive NSCLC: Post-Hoc Analyses of LUX-Lung 3/6: Track: Advanced NSCLC. PMID- 27676533 TI - P1.47: ABOUND.sqm QoL by Response: Interim Analysis of Squamous NSCLC Pts Treated With nab-Paclitaxel/Carboplatin Induction Therapy: Track: Advanced NSCLC. PMID- 27676534 TI - P1.48: nab-Paclitaxel + Carboplatin in Advanced Non-Small Cell Lung Cancer: Outcomes in Elderly Patients With Squamous Histology: Track: Advanced NSCLC. PMID- 27676535 TI - P1.50: Long-Term Safety and Efficacy of Darbepoetin Alfa in Subjects With Advanced Stage NSCLC Receiving Multi-Cycle Chemotherapy: Track: Supportive Care and Others. PMID- 27676536 TI - P1.49 (also presented as PD1.05): The Genomics of Young Emergent Lung Cancer: Track: Advanced NSCLC. PMID- 27676537 TI - P1.51: Impact of Regulatory Delays in Drug Approval: Mortality and Morbidity Due to With Lack of Access to Crizotinib in Brazil: Track: Supportive Care and Others. PMID- 27676538 TI - P2.01: LUME-MeSO: Phase II/III Study of Nintedanib + Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Track: SCLC, Mesothelioma, Thymoma. PMID- 27676539 TI - P2.02: Thymic Malignancies. A Single Institution Series From 2006-2016: Track: SCLC, Mesothelioma, Thymoma. PMID- 27676541 TI - P2.04: Characteristics and Long Term Outcomes of Advanced Pleural Mesothelioma in Latin America (MeSO-CLICaP): Track: SCLC, Mesothelioma, Thymoma. PMID- 27676540 TI - P2.03: Treatment of Malignant Pleural Mesothelioma Beyond First-Line Among Hispanics (MeSO-CLICaP): Track: SCLC, Mesothelioma, Thymoma. PMID- 27676542 TI - P2.05: The Synthetic Peptide CIGB-300 Inhibits NF-kappaB Translocation Affecting the Survival and Chemoresistance of NSCLC Cell Lines: Track: Biology and Pathogenesis. PMID- 27676543 TI - P2.06: Exosomal miRNA Analysis in Non-Small Cell Lung Cancer: New Liquid Biomarker?: Track: Biology and Pathogenesis. PMID- 27676544 TI - P2.07: Evaluation of Different Exosomal RNA Isolation Methods in NSCLC Liquid Biopsies: Track: Biology and Pathogenesis. PMID- 27676545 TI - P2.08: Gene Fusions Detected in Non-Small Cell Lung Carcinoma (NSCLC) and Small Cell Lung Carcinoma (SCLC): Track: Biology and Pathogenesis. PMID- 27676546 TI - P2.09: cMET in NSCLC: Expression, Amplification and Mutations: Track: Biology and Pathogenesis. PMID- 27676547 TI - P2.10: Clinical and Pathological Characteristics of ALK Positive Lung Cancer Patients. Instituto Oncologico Nacional - Panama: Track: Biology and Pathogenesis. PMID- 27676548 TI - P2.12: Treatment Response in Patients With ALK Immunohistochemistry (IHC) Positive With Fish Negative: Track: Pathology. PMID- 27676549 TI - P2.13: Testing Profiles in NSCLC Biopsy Samples: Multi-Institutional Study in Cordoba: Track: Pathology. PMID- 27676550 TI - P2.14: Lung Cancer as Second Primary Cancer in Two Patients in a Reference Hospital in Latin America: A Case Report: Track: Pathology. PMID- 27676551 TI - P2.15: Treatment Outcome of Metastatic Breast Angiosarcoma to the Lung, in a Reference Hospital in Latin America: A Case Report: Track: Pathology. PMID- 27676552 TI - P2.16: Atypical Adenomatous Hyperplasia (AAH) in a Patient With a Primary Carcinoid Lung Tumor: Case-Report: Track: Pathology. PMID- 27676553 TI - P2.17: Incidence of Non-Small Cell Lung Cancer Biomarkers in Panama; Demographyc, Clinic and Histopathological Features: Track: Pathology. PMID- 27676554 TI - P2.18: Rapid On-Site Evaluation (ROSE) Technique: Experience in the Pulmonology Unit of a Reference Hospital in Latin America: Track: Pathology. PMID- 27676555 TI - P2.19 (also presented as PD1.04): Infrequent Staining Patterns in ALK Immunohistochemistry: Correlation With Fish Analysis: Track: Pathology. PMID- 27676556 TI - P2.21: Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA) Experience in a Reference Hospital in Latin America: Track: Bronchoscopy. PMID- 27676557 TI - P2.20: Malignant Obstruction of the Central Airway by an EBV(+) Diffuse Large B Cell Lymphoma: An Unusual Presentation: Track: Bronchoscopy. PMID- 27676558 TI - P2.22: Therapeutic Bronchoscopy in Multimodal Therapy for the Management of Central Airway Obstruction in Latin America: Track: Bronchoscopy. PMID- 27676559 TI - P2.23: Effectiveness of Methylnaltrexone Bromide as a Treatment for Opioid Induced Constipation in NSCLC Patients: Track: Supportive Care and Others. PMID- 27676560 TI - P2.24: Pulmonary-Epithelioid Hemangioendothelioma: A Case Report of Spontaneous Regression: Track: Supportive Care and Others. PMID- 27676561 TI - P2.26: Reference to Palliative Care in Patients With Advanced Lung Cancer Treated With Systemic Therapy. Ion, Panama: Track: Supportive Care and Others. PMID- 27676562 TI - P2.27: Blood Supplement Research of the Percutaneous Inoculated Canine Transmissible Venereal Tumor Lung Cancer Model: Track: Supportive Care and Others. PMID- 27676563 TI - P2.28: Image-Guided Radiofrecuency Ablation of Lung Metastases. A Single Cancer Center Experience in Panama: Track: Supportive Care and Others. PMID- 27676564 TI - P2.31: Understanding Factors Influencing Self-Referral of Patients From Resource Limited Institutions Seeking Lung Cancer Care: Track: Supportive Care and Others. PMID- 27676565 TI - P2.29: An Approach to Ensure Adequate Intake of Nutrients for Patients With Lung Cancer: Track: Supportive Care and Others. PMID- 27676566 TI - P2.32: Survival Assessment of Non-Small Cell Lung Neoplasia Patients in Advanced Stage Treated With the CIMAvax-EGF Vaccine: Track: Immunotherapy. PMID- 27676567 TI - P2.33: Safety Profile of Nivolumab Administered as 30-Minute (MIN) Infusion: Analysis of Data From Checkmate 153: Track: Immunotherapy. PMID- 27676568 TI - P2.34: Vaxira and CIMAvax-EGF Therapeutic Vaccines Combination in the Advanced NSCLC Treatment: Track: Immunotherapy. PMID- 27676569 TI - P2.35: Nivolumab vs Docetaxel in Advanced NSCLC: CheckMate 017/057 2-Y Update and Exploratory Cytokine Profile Analysis: Track: Immunotherapy. PMID- 27676571 TI - P2.37: A Case of Immune-Mediated Pneumonitis?: Track: Immunotherapy. PMID- 27676570 TI - P2.36: Nivolumab (nivo) in Patients (pts) With Advanced (adv) NSCLC and Central Nervous System (CNS) Metastases (mets): Track: Immunotherapy. PMID- 27676572 TI - P2.38: Nivolumab in Clinical Practice: Real World Experience in an Argentina Oncologic Center: Track: Immunotherapy. PMID- 27676573 TI - P2.39: Long-Term OS for Patients With Advanced NSCLC Enrolled in the KEYNOTE-001 Study of Pembrolizumab: Track: Immunotherapy. PMID- 27676574 TI - P2.40: CIMAvaxEGF Vaccine for the Treatment of Real-World NSCLC Patients: Track: Immunotherapy. PMID- 27676575 TI - P2.41 (also presented as PD1.06): Pembrolizumab vs Docetaxel for Previously Treated NSCLC (KEYNOTE-010): Archival vs New Tumor Samples for PD-L1 Assessment: Track: Immunotherapy. PMID- 27676576 TI - P2.42: An Immunotherapy Approach to Overcoming Resistance to Second and Third Generation EGFR Inhibitors: Track: Immunotherapy. PMID- 27676577 TI - P2.43: Pembrolizumab vs Platinum-Based Chemotherapy for PD-L1+ NSCLC: Phase 3, Randomized, Open-Label KEYNOTE-042 (NCT02220894): Track: Immunotherapy. PMID- 27676578 TI - P2.44: An Update of a Pooled Analysis of Nivolumab for the Treatment of Advanced NSCLC and the Role of PD-L1 as a BIOMARKER: Track: Immunotherapy. PMID- 27676579 TI - P2.45: An Estimate of the Economic Impact of Treatment of NSCLC With Immunotherapy Relative to PD-L1 Expression in Brazil: Track: Immunotherapy. PMID- 27676580 TI - P2.46 (also presented as PD1.01): LCSS as a Marker of Treatment Benefit With Nivolumab vs Docetaxel in Pts With Advanced Non-Squamous NSCLC From Checkmate 057: Track: Immunotherapy. PMID- 27676581 TI - P2.47 (also presented as PD1.02): The Role of PD-L1 Expression as a Predictive Biomarker in Advanced NSCLC: An Update of a Network Meta-Analysis: Track: Immunotherapy. PMID- 27676582 TI - Plasmonic Hot Electron Solar Cells: The Effect of Nanoparticle Size on Quantum Efficiency. AB - Gold nanoparticles located at a metal oxide/hole conductor interface generate photocurrents upon visible light illumination. We demonstrate that the quantum efficiency of this process depends on the nanoparticle size. Gold nanoparticles (5 nm) show a maximum absorbed photon-to-electron conversion efficiency (APCE) of 13.3%. For increasing particle sizes, the average APCE decreases to 3.3% for the largest particles (40 nm) investigated. Three possible causes for this efficiency change are discussed. PMID- 27676583 TI - Effects of sweet flavorings and nicotine on the appeal and sensory properties of e-cigarettes among young adult vapers: Application of a novel methodology. AB - INTRODUCTION: Product characteristics that impact e-cigarette appeal by altering the sensory experience of vaping need to be identified to formulate evidence based regulatory policies. While products that contain sweet flavorings and produce a "throat hit" (i.e., desirable airway irritation putatively caused by nicotine) are anecdotally cited as desirable reasons for vaping among young adults, experimental evidence of their impact on user appeal is lacking. This experiment applied a novel laboratory protocol to assess whether: (1) sweet flavorings and nicotine affect e-cigarette appeal; (2) sweet flavorings increase perceived sweetness; (3) nicotine increases throat hit; and (4) perceived sweetness and throat hit are associated with appeal. METHODS: Young adult vapers (N=20; age 19-34) self-administered 20 standardized doses of aerosolized e cigarette solutions varied according to a 3 flavor (sweet [e.g., cotton candy] vs. non-sweet [e.g., tobacco-flavored] vs. flavorless)*2 nicotine (6mg/mL nicotine vs. 0mg/mL [placebo]) double-blind, cross-over design. Participants rated appeal (liking, willingness to use again and perceived monetary value), perceived sweetness and throat hit strength after each administration. RESULTS: Sweet-flavored (vs. non-sweet and flavorless) solutions produced greater appeal and perceived sweetness ratings. Nicotine produced greater throat hit ratings than placebo, but did not significantly increase appeal nor interact with flavor effects on appeal. Controlling for flavor and nicotine, perceived sweetness was positively associated with appeal ratings; throat hit was not positively associated with appeal. CONCLUSIONS: Further identification of compounds in e cigarette solutions that enhance sensory perceptions of sweetness, appeal, and utilization of e-cigarettes are warranted to inform evidence-based regulatory policies. PMID- 27676585 TI - Exploring Home Care Interventions for Frail Older People in Belgium: A Comparative Effectiveness Study. AB - OBJECTIVES: To examine the effects of home care interventions for frail older people in delaying permanent institutionalization during 6 months of follow-up. DESIGN: Longitudinal quasi-experimental research study, part of a larger study called Protocol 3. SETTING: Community care in Belgium. PARTICIPANTS: Frail older adults who received interventions (n = 4,607) and a comparison group of older adults who did not (n = 3,633). Organizations delivering the interventions included participants provided they were aged 65 and older, frail, and at risk of institutionalization. A comparison group was established consisting of frail older adults not receiving any interventions. INTERVENTION: Home care interventions were identified as single component (occupational therapy (OT), psychological support, night care, day care) or multicomponent. The latter included case management (CM) in combination with OT and psychological support or physiotherapy, with rehabilitation services, or with OT alone. MEASUREMENTS: The interRAI Home Care (HC) was completed at baseline and every 6 months. Data from a national database were used to establish a comparison group. Relative risks of institutionalization and death were calculated using Poisson regression for each type of intervention. RESULTS: A subgroup analysis revealed that 1,999 older people had mild impairment, and 2,608 had moderate to severe impairment. Interventions providing only OT and interventions providing CM with rehabilitation services were effective in both subpopulations. CONCLUSION: This research broadens the understanding of the effects of different types of community care interventions on the delay of institutionalization of frail older people. This information can help policy-makers to plan interventions to avoid early institutionalization. PMID- 27676586 TI - Synthesis of Nitrogen Heterocycles via Photochemical Ring Opening of Pyridazine N Oxides. AB - A photochemical method for the direct synthesis of 1H-pyrazoles from pyridazine N oxides was developed. This chemistry features a regioselective approach to nonsymmetrically substituted pyridazine N-oxides. Herein, we highlight the first strategic use of photoinduced ring-opening reactions of 1,2-diazine N-oxides for the preparative synthesis of nitrogen heterocycles. PMID- 27676584 TI - A beginner's guide to atomic force microscopy probing for cell mechanics. AB - Atomic Force microscopy (AFM) is becoming a prevalent tool in cell biology and biomedical studies, especially those focusing on the mechanical properties of cells and tissues. The newest generation of bio-AFMs combine ease of use and seamless integration with live-cell epifluorescence or more advanced optical microscopies. As a unique feature with respect to other bionanotools, AFM provides nanometer-resolution maps for cell topography, stiffness, viscoelasticity, and adhesion, often overlaid with matching optical images of the probed cells. This review is intended for those about to embark in the use of bio AFMs, and aims to assist them in designing an experiment to measure the mechanical properties of adherent cells. In addition to describing the main steps in a typical cell mechanics protocol and explaining how data is analysed, this review will also discuss some of the relevant contact mechanics models available and how they have been used to characterize specific features of cellular and biological samples. Microsc. Res. Tech. 80:75-84, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27676587 TI - Improved production of propionic acid using genome shuffling. AB - Traditionally derived from fossil fuels, biological production of propionic acid has recently gained interest. Propionibacterium species produce propionic acid as their main fermentation product. Production of other organic acids reduces propionic acid yield and productivity, pointing to by-products gene-knockout strategies as a logical solution to increase yield. However, removing by-product formation has seen limited success due to our inability to genetically engineer the best producing strains (i.e. Propionibacterium acidipropionici). To overcome this limitation, random mutagenesis continues to be the best path towards improving strains for biological propionic acid production. Recent advances in next generation sequencing opened new avenues to understand improved strains. In this work, we use genome shuffling on two wild type strains to generate a better propionic acid producing strain. Using next generation sequencing, we mapped the genomic changes leading to the improved phenotype. The best strain produced 25% more propionic acid than the wild type strain. Sequencing of the strains showed that genomic changes were restricted to single point mutations and gene duplications in well-conserved regions in the genomes. Such results confirm the involvement of gene conversion in genome shuffling as opposed to long genomic insertions. PMID- 27676588 TI - Risk assessment with actuarial and clinical methods: Measurement and evidence based practice. AB - Child welfare agencies have adopted assessment tools and instruments to inform the level of risk and guide the agency's level of intervention with the family. Actuarial assessments may be more uniform but inflexible with respect to practice wisdom whereas clinical or consensus-based assessments are more comprehensive and intuitive but lack objectivity. The purpose of the current study is to compare clinical and actuarial methods of risk assessment used by child welfare workers to make decisions about substantiation and services. The current study examined the (1) association between clinical and actuarial dimensions, (2) association between actuarial dimensions and outcomes, (3) association between clinical dimensions and outcomes, (4) caseworker primary use of actuarial dimensions, and (5) caseworker supplementary use of actuarial dimensions. Findings indicated that the actuarial may not be solely predictive of agency intensity with respect to case decision and service provision. Our findings suggest that dual-measurement does inform intensity, and we speculate from these findings that the measures may be involved with decision-making in a complex way. This study may be best viewed as a means by which researchers begin to parse how decisions are made; with this information, instruments may be better tailored to facilitate clinical, critical thought. PMID- 27676594 TI - Decarboxylation Facilitated by Carbocation Formation and Rearrangement during Steam Distillation of Vetiver Oil. AB - Density functional theory (DFT) calculations are used to probe the validity of mechanistic proposals for the conversion of isozizanoic acid to 12-norisoziza-5 ene, a reaction that occurs during steam distillation of vetiver oil. While this conversion corresponds overall to a simple decarboxylation, a multistep mechanism involving carbocation intermediates is supported by the computational results. PMID- 27676596 TI - Radiation Protection, Safety and Security Issues in Ghana. AB - Although the use of radioisotopes in Ghana began in 1952, the Radiation Protection Board of Ghana was established in 1993 and served as the national competent authority for authorization and inspection of practices and activities involving radiation sources until 2015. The law has been superseded by an Act of Parliament, Act 895 of 2015, mandating the Nuclear Regulatory Authority of Ghana to take charge of the regulation of radiation sources and their applications. The Radiation Protection Institute in Ghana provided technical support to the regulatory authority. Regulatory and service activities that were undertaken by the Institute include issuance of permits for handling of a radiation sources, authorization and inspection of radiation sources, radiation safety assessment, safety assessment of cellular signal towers, and calibration of radiation emitting equipment. Practices and activities involving application of radiation are brought under regulatory control in the country through supervision by the national competent authority. PMID- 27676597 TI - Dose Assessment and Considerations When a Radioactive Seed is Unrecoverable in a Breast Surgical Patient. AB - Excision of non-palpable breast tumors in cancer patients has been routinely performed using surgical clips and wires placed under mammographic or ultrasound guidance. An alternative method exists for performing these surgeries without surgical wires and this approach has become more widely used at Oncology Centers in the United States. Roswell Park Cancer Institute (RPCI) performs many of their breast surgeries with radioactive seeds and has enjoyed favorable outcomes along with an enhanced patient experience. There are some inherent difficulties with using radioactive seeds, and seed tracking can be a problem during surgical procedures. When a seed is misplaced, an extensive search is conducted in an effort to locate the misplaced seed. Every attempt to recover these radioactive seeds should be made unless patient safety is jeopardized. If the seed is unrecoverable, then a dose assessment must be performed and corrective action determined. It is important to have adequate policies and procedures in place to prevent these rare occurrences. They should be treated as a radioactive medical event. PMID- 27676595 TI - How Patients View Lung Cancer Screening. The Role of Uncertainty in Medical Decision Making. AB - RATIONALE: Radiographic lung cancer screening guidelines and coverage requirements warrant a shared decision-making process. Guidance is needed regarding how to conduct shared decision making effectively. A useful organizing theme should include consideration of a patient's response to and tolerance of uncertainty associated with lung cancer screening. OBJECTIVES: The objectives of this study are to: (1) describe how patients respond to specific categories of uncertainty in the context of lung cancer screening, and (2) inform strategies for addressing concerns about uncertainty as part of the shared decision making. METHODS: We performed two series of structured interviews on participants in a convenience sample of current or former cigarette smokers recruited from primary care and pulmonary practices in Philadelphia. An interview guide included prompts related to benefits, harms, and responses to general and specific types of uncertainty (stochastic, statistical, and evidentiary) associated with lung cancer screening. Interviews were audio-recorded, transcribed, and independently coded by two investigators. An inductive analysis was conducted, and major themes were identified. MEASUREMENTS AND MAIN RESULTS: Twenty-two adults participated in the study. Sixty-eight percent were men, 72% were black or African American, and 50% met U.S. Preventive Services Task Force criteria for lung cancer screening. The primary themes to emerge from our study were: (1) the desire to decrease uncertainty may motivate lung cancer screening decisions; (2) uncertainty is an attribute of health states that impacts how patients weigh benefits and harms of lung cancer screening; (3) patient understanding and tolerance of uncertainty varies across stochastic, statistical, and evidentiary uncertainty; and (4) provider-patient communication may mitigate intolerance of uncertainty in the context of lung cancer screening. CONCLUSIONS: A systematic approach to understanding and addressing patients' concerns about uncertainty in the context of lung cancer screening can guide a patient-centered approach to shared decision making. The results of this study can inform provider-patient communication strategies regarding the decision to perform radiographic lung cancer screening. PMID- 27676598 TI - Simultaneous Determination of the Depth of an Embedded Source and its Radioactivity in the Medium. AB - The simultaneous determination of the depth of an embedded source and its radioactivity in the medium at the environmental surveys is a very useful and advisable method for an in-situ gamma-ray measurement with respect to the time and cost constraint. An algorithm for the determination of the source depth and its radioactivity in the medium was developed using the information on the uncollided photon fluences and measured net count rates, which mean not scattered fluences and background subtracted count rate, at the detector positions. Uncollided photon fluences were calculated at several source depths in the medium as well as at detector positions from the Monte Carlo N-Particle (MCNP) simulation. The results were then used to establish a database to output their values according to the source depth in the medium by inputting the photon energy and detector position from the medium. A simple program about the simultaneous determination of two variables was applied to the results on a task to find out the depth and activity of Cs and Cs at in-situ gamma-ray spectrometry. Less than 10% and 15% differences compared with the real values at the source depth and radioactivity, respectively, were achieved using the developed program. PMID- 27676599 TI - Contributions of Various Radiological Sources to Background in a Suburban Environment. AB - This work is a brief overview and comparison of dose rates stemming from both indoor and outdoor natural background radiation and household objects within a suburban environment in North Carolina. Combined gamma and beta dose rates were taken from indoor objects that ranged from the potassium in fruit to the americium in smoke detectors. For outdoor measurements, various height and time data samples were collected to show fluctuations in dose rate due to temperature inversion and geometric attenuation. Although each sample tested proved to have a statistically significant increase over background using Students t-test, no sample proved to be more than a minor increase in natural radiation dose. The relative contributions from natural radioactivity such as potassium in foods and common household items are shown to be easily distinguished from background using standard handheld instrumentation when applied in a systematic, methodological manner. PMID- 27676600 TI - RSO Interview with Michael Ocasio. PMID- 27676601 TI - Using Geographic Information Systems to Determine Site Suitability for a Low Level Radioactive Waste Storage Facility: Erratum. PMID- 27676602 TI - Specific Hydrogen-Bond-Mediated Recognition and Modification of Surfaces Using Complementary Functionalized Polymers. AB - Specific hydrogen-bonding interactions between polymers and surface-tethered recognition elements were used to selectively modify self-assembled monolayers (SAMs) on gold. The interfacial recognition processes were followed by observing frequency changes of thymine-SAM modified quartz crystal microbalance (QCM) chips during adsorption of diamidopyridine-functionalized (DAP) polystyrene from a nonpolar solvent. QCM studies combined with X-ray photoelectron spectroscopy (XPS), water contact angle, and ellipsometry measurements of the polymer-modified surfaces demonstrate the selectivity of the polymer-surface hydrogen-bonding interactions. These studies also indicate that the degree of recognition element functionalization of both the polymer and the surface is crucial in determining the rate, selectivity, and coverage of polymer on the surface. PMID- 27676603 TI - Is early breast milk fortification more effective in preterm infants?: a clinical trial. AB - OBJECTIVE: Breast feeding alone does not provide adequate nutrition for growth in preterm infants; therefore, fortifiers are added when over 70-80 cc/kg/day of breast milk is tolerated. As there are few studies comparing early and late breast milk fortification, the following study was conducted. STUDY DESIGN: This double-blind clinical trial was performed on 80 preterm infants (gestational age of 28-34 weeks, birth weight <2 kg). The newborns were randomly divided into two groups to receive either early or late fortification. The primary and secondary outcomes were the difference in growth indices and complications (including feeding intolerance, necrotizing enterocolitis (NEC), and septicemia) between the two groups, respectively. RESULTS: Both groups showed increases in growth indices; however, there was no statistically significant difference in increments of growth indices and complications between the two groups. CONCLUSION: Our findings suggest that early fortification from the first feeding in neonates with exclusive breast feeding did not improve growth in the first 4 weeks in preterm neonates in comparison with late fortification; so early fortification may not be cost effective. PMID- 27676605 TI - Structural and lipid-binding characterization of human annexin A13a reveals strong differences with its long A13b isoform. AB - Annexin A13 is the founder member of the vertebrate family of annexins, which are comprised of a tetrad of unique conserved domains responsible for calcium dependent binding to membranes. Its expression is restricted to epithelial intestinal and kidney cells. Alternative splicing in the N-terminal region generates two isoforms, A13a and A13b, differing in a deletion of 41 residues in the former. We have confirmed the expression of both isoforms in human colon adenocarcinoma cells at the mRNA and protein levels. We have cloned, expressed, and purified human annexin A13a for the first time to analyze its structural characteristics. Its secondary structure and thermal stability differs greatly from the A13b isoform. The only tryptophan residue (Trp186) is buried in the protein core in the absence of calcium but is exposed to the solvent after calcium binding even though circular dichroism spectra are quite similar. Non myristoylated annexin A13a binds in a calcium-dependent manner to acidic phospholipids but not to neutral or raft-like liposomes. Calcium requirements for binding to phosphatidylserine are around 6-fold lower than those required by the A13b isoform. This fact could account for the different subcellular localization of both annexins as binding to basolateral membranes seems to be calcium dependent and myristoylation-independent. PMID- 27676604 TI - Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families. AB - Tropane alkaloids and their derivatives are anticholinergic drugs with narrow therapeutic range. Here we characterize the organic cation transporters from the SLC22 (OCT1, OCT2, and OCT3) and the SLC47 families (MATE1 and MATE2-K) as potential mediators of the renal and extra-renal excretion, the two major roads of elimination of these substances. All analyzed compounds inhibited and the quaternary amine derivatives ipratropium and trospium were strongly transported by OCTs and MATEs. Overexpression of OCTs or MATEs in HEK293 cells resulted in an up to 63-fold increase in the uptake of ipratropium (Km of 0.32 MUm to OCT2 and Vmax of 3.34 nmol*mg protein-1*min-1 to MATE1). The transcellular transport of ipratropium was 16-fold higher in OCT2-MATE1 and 10-fold higher in OCT1-MATE1 overexpressing compared to control MDCKII cells. Genetic polymorphisms in OCT1 and OCT2 affected ipratropium uptake and clinically relevant concentration of ondansetron and pyrithiamine inhibited ipratropium uptake via MATEs by more than 90%. This study suggests that OCT1, OCT2 and MATEs may be strongly involved in the renal and extra-renal elimination of ipratropium and other quaternary amine alkaloids. These substances have a notoriously narrow therapeutic range and the drug-drug interactions suggested here should be further critically evaluated in humans. PMID- 27676606 TI - Prevalence of pseudonatremia in a clinical laboratory - role of the water content. AB - BACKGROUND: Sodium concentration is a frequently used marker to discriminate between differential diagnoses or for clinical follow-up. Pseudonatremia, as a result of indirect ion-selective electrode (ISE) measurements in automated chemistry analyzers, can lead to incorrect diagnosis and treatment. We investigated whether the estimated water content, based on total protein and lipid concentrations, can be used to reduce diagnoses of pseudonatremia. METHODS: Indirect and direct ISE measurements of sodium were compared in blood samples from intensive care unit (ICU) (n = 98) and random non-ICU patients (n = 100). Differences between direct measurements using whole blood and lithium-heparin plasma were also determined. Water content, estimated by a linear combination of total protein and lipid concentrations, was used to correct indirectly measured sodium concentrations. The prevalence of pseudonatremia was evaluated in the ICU patient group. RESULTS: An absolute difference of 3 mmol/L was observed between direct measurements using lithium-heparin plasma and whole blood, with higher concentrations in plasma. Additionally, we observed that differences between indirect and direct measurements displayed a linear relationship with the estimated water content. The prevalence of pseudohypernatremia after indirect measurements (32%) was reduced when measurements were corrected for water content (19%). CONCLUSIONS: In critically ill patients, sodium concentrations should be preferably measured by direct measurements. Whole blood is the preferred material for these measurements. For routine sodium analyses in other patients, correction using the estimated water content appears promising in reducing the prevalence of pseudohypernatremia by indirect measurements. PMID- 27676607 TI - The Bacterial Signature of Leptospermum scoparium (Manuka) Reveals Core and Accessory Communities with Bioactive Properties. AB - Leptospermum scoparium or manuka is a New Zealand native medicinal plant that produces an essential oil with antimicrobial properties. This is the first study to investigate the structure and bioactivity of endophytic bacteria in manuka by using a combination of cultivation-independent (DGGE) and dependent approaches. A total of 23 plants were sampled across three sites. Plants were considered either immature (3-8 years) or mature (>20 years). The endophyte community structure and richness was affected by plant tissue and bacterial communities became more stable and uniform as plant maturity increased. A total of 192 culturable bacteria were recovered from leaves, stems and roots. Some bacterial isolates showed in vitro biocontrol activity against two fungal pathogens, Ilyonectria liriodendri and Neofusicoccum luteum and a bacterial pathogen, Pseudomonas syringae pv. actinidiae. A high proportion of bacterial endophytes could produce siderophores and solubilise phosphate in vitro. Gammaproteobacteria was the most variable class, representing the majority of cultivated bacteria with bioactivity. PMID- 27676608 TI - Synthesis and antitumor activity of (-)-bassianolide in MDA-MB 231 breast cancer cells through cell cycle arrest. AB - The high level of interest in the cyclodepsipeptides family in the natural products stems from their diverse range of biological activities. One of the cyclodepsipeptides, (-)-bassianolide, represents rich pharmacophores with diverse biological activities including potential cytotoxicity to various cancer cells. Efficient total synthesis of (-)-bassianolide was designed and achieved in nine steps, with significant improvements in the overall yield of 46.8% (vs. 7.2% yield in previous synthesis) using Ghosez's chloroenamine reagent under mild conditions. The cytotoxicity of the (-)-bassianolide was evaluated against five human tumor cells, and the results showed that the (-)-bassianolide displayed significant cytotoxicity against A549, SK-OV-3, HepG2, HCT-15, MCF-7 and MDA-MB 231 cell lines with IC50 values of 7.24, 8.44, 15.39, 6.40, 11.42 and 3.98 MUg/mL respectively. Specifically, (-)-bassianolide induced G0/G1 arrest associated with a decrease of cyclin A, D1 and an increase of p53, MDM2, and p21 expression in MDA-MB 231 cells. These results demonstrate that (-)-bassianolide possesses antitumor activities via arresting of the cell cycle and the synthetic approach features an efficient and mild method for the formation of amide bonds through three inter- and intramolecular coupling reactions. PMID- 27676610 TI - Electrostatic Contributions to Protein Quinary Structure. AB - There are four well-known levels of protein structure: primary (amino acid sequence), secondary (helices, sheets and turns), tertiary (three-dimensional structure) and quaternary (specific protein-protein interactions). The fifth level remains largely undefined because characterization of quinary structure, the transient but essential macromolecular interactions that organize the crowded cellular interior, requires the measurement of equilibrium thermodynamic parameters in living cells. We have overcome this challenge by quantifying the pH dependence of quinary interactions in living Escherichia coli cells using the B1 domain of protein G (GB1, 6.2 kDa). To accomplish this goal, we buffered the cellular interior and used NMR-detected amide proton exchange to quantify the free energy of unfolding in cells. At neutral pH, the unfolding free energy in cells is comparable to that in buffered solution. As the pH decreases, the increased number of attractive interactions between E. coli proteins and GB1 destabilizes the protein in cells relative to buffer alone. The data show that electrostatic interactions contribute to quinary structure. PMID- 27676609 TI - Value and Anisotropy of the Electron and Hole Mass in Pure Wurtzite InP Nanowires. AB - The effective mass of electrons and holes in semiconductors is pivotal in determining the dynamics of carriers and their confinement energy in nanostructured materials. Surprisingly, this quantity is still unknown in wurtzite (WZ) nanowires (NWs) made of III-V compounds (e.g., GaAs, InAs, GaP, InP), where the WZ phase has no bulk counterpart. Here, we investigate the magneto-optical properties of InP WZ NWs grown by selective-area epitaxy that provides perfectly ordered NWs featuring high-crystalline quality. The combined analysis of the energy of free exciton states and impurity levels under magnetic field (B up to 29 T) allows us to disentangle the dynamics of oppositely charged carriers from the Coulomb interaction and thus to determine the values of the electron and hole effective mass. By application of B? along different crystallographic directions, we also assess the dependence of the transport properties with respect to the NW growth axis (namely, the WZ c axis). The effective mass of electrons along c is me? = (0.078 +/- 0.002) m0 (m0 is the electron mass in vacuum) and perpendicular to c is me? = (0.093 +/- 0.001) m0, resulting in a 20% mass anisotropy. Holes exhibit a much larger (~320%) and opposite mass anisotropy with their effective mass along and perpendicular to c equal to mh? = (0.81 +/- 0.18) m0 and mh? = (0.250 +/- 0.016) m0, respectively. While no full consensus is found with current theoretical results on WZ InP, our findings show trends remarkably similar to the experimental data available in WZ bulk materials, such as InN, GaN, and ZnO. PMID- 27676611 TI - A Comparison of Midwife-Led and Medical-Led Models of Care and Their Relationship to Adverse Fetal and Neonatal Outcomes: A Retrospective Cohort Study in New Zealand. AB - BACKGROUND: Internationally, a typical model of maternity care is a medically led system with varying levels of midwifery input. New Zealand has a midwife-led model of care, and there are movements in other countries to adopt such a system. There is a paucity of systemic evaluation that formally investigates safety related outcomes in relationship to midwife-led care within an entire maternity service. The main objective of this study was to compare major adverse perinatal outcomes between midwife-led and medical-led maternity care in New Zealand. METHODS AND FINDINGS: This was a population-based retrospective cohort study. Participants were mother/baby pairs for all 244,047 singleton, term deliveries occurring between 1 January 2008 and 31 December 2012 in New Zealand in which no major fetal, neonatal, chromosomal or metabolic abnormality was identified and the mother was first registered with a midwife, obstetrician, or general practitioner as lead maternity carer. Main outcome measures were low Apgar score at five min, intrauterine hypoxia, birth-related asphyxia, neonatal encephalopathy, small for gestational age (as a negative control), and mortality outcomes (perinatal related mortality, stillbirth, and neonatal mortality). Logistic regression models were fitted, with crude and adjusted odds ratios (ORs) generated for each outcome for midwife-led versus medical-led care (based on lead maternity carer at first registration) with 95% confidence intervals. Fully adjusted models included age, ethnicity, deprivation, trimester of registration, parity, smoking, body mass index (BMI), and pre-existing diabetes and/or hypertension in the model. Of the 244,047 pregnancies included in the study, 223,385 (91.5%) were first registered with a midwife lead maternity carer, and 20,662 (8.5%) with a medical lead maternity carer. Adjusted ORs showed that medical-led births were associated with lower odds of an Apgar score of less than seven at 5 min (OR 0.52; 95% confidence interval 0.43-0.64), intrauterine hypoxia (OR 0.79; 0.62-1.02), birth-related asphyxia (OR 0.45; 0.32-0.62), and neonatal encephalopathy (OR 0.61; 0.38-0.97). No association was found between lead carer at first registration and being small for gestational age (SGA), which was included as a negative control (OR 1.00; 0.95-1.05). It was not possible to definitively determine whether one model of care was associated with fewer infant deaths, with ORs for the medical-led model compared with the midwife-led model being 0.80 (0.54-1.19) for perinatal related mortality, 0.86 (0.55-1.34) for stillbirth, and 0.62 (0.25-1.53) for neonatal mortality. Major limitations were related to the use of routine data in which some variables lacked detail; for example, we were unable to differentiate the midwife-led group into those who had received medical input during pregnancy and those who had not. CONCLUSIONS: There is an unexplained excess of adverse events in midwife-led deliveries in New Zealand where midwives practice autonomously. The findings are of concern and demonstrate a need for further research that specifically investigates the reasons for the apparent excess of adverse outcomes in mothers with midwife-led care. These findings should be interpreted in the context of New Zealand's internationally comparable birth outcomes and in the context of research that supports the many benefits of midwife-led care, such as greater patient satisfaction and lower intervention rates. PMID- 27676612 TI - Unique Axial Imidazole Geometries of Fully Halogenated Iron(II) Porphyrin Complexes: Crystal Structures and Mossbauer Spectroscopic Studies. AB - The synthesis and characterization of several electron-poor iron(II) porphyrin (FeTFPPBr8) complexes with axial imidazole ligands are reported. The single crystal X-ray structures have been studied by a combination of crystal packing and Hirshfeld surface calculations, which explained the unusual axial-ligand geometries, e.g., the strong tilt of the Fe-NIm bonds and the imidazole planes. The six-coordinate [Fe(TFPPBr8)(1-MeIm)2] was studied by multiple-temperature solid-state Mossbauer spectroscopy, which suggested that it is a low-spin complex with delta ~ 0.32-0.38 mm/s and DeltaEQ ~ 1.0 mm/s. PMID- 27676613 TI - News Stories of Intimate Partner Violence: An Experimental Examination of Participant Sex, Perpetrator Sex, and Violence Severity on Seriousness, Sympathy, and Punishment Preferences. AB - This study experimentally examines the effects of participant sex, perpetrator sex, and severity of violence on perceptions of intimate partner violence (IPV) seriousness, sympathy toward the victim, and punishment preferences for the perpetrator. Participants (N = 449) were randomly assigned to a condition, exposed to a composite news story, and then completed a survey. Ratings of seriousness of IPV for stories with male perpetrators were significantly higher than ratings of seriousness for stories with female perpetrators. Men had significantly higher sympathy for female victims in any condition than for male victims in the weak or strong severity of violence conditions. Men's sympathy for male victims in the fatal severity of violence condition did not differ from their sympathy for female victims. Women had the least sympathy for female victims in the weak severity condition and men in the weak or strong severity conditions. Women reported significantly higher sympathy for female victims in the strong and fatal severity of violence conditions. Women's ratings of sympathy for male victims in the fatal severity of violence condition were statistically indistinguishable from any other group. Participants reported stronger punishment preferences for male perpetrators and this effect was magnified among men. Theoretical implications are presented with attention provided to practical considerations about support for public health services. PMID- 27676614 TI - The Contribution of Object Shape and Surface Properties to Object Ensemble Representation in Anterior-medial Ventral Visual Cortex. AB - Our visual system can extract summary statistics from large collections of objects without forming detailed representations of the individual objects in the ensemble. In a region in ventral visual cortex encompassing the collateral sulcus and the parahippocampal gyrus and overlapping extensively with the scene selective parahippocampal place area (PPA), we have previously reported fMRI adaptation to object ensembles when ensemble statistics repeated, even when local image features differed across images (e.g., two different images of the same strawberry pile). We additionally showed that this ensemble representation is similar to (but still distinct from) how visual texture patterns are processed in this region and is not explained by appealing to differences in the color of the elements that make up the ensemble. To further explore the nature of ensemble representation in this brain region, here we used PPA as our ROI and investigated in detail how the shape and surface properties (i.e., both texture and color) of the individual objects constituting an ensemble affect the ensemble representation in anterior-medial ventral visual cortex. We photographed object ensembles of stone beads that varied in shape and surface properties. A given ensemble always contained beads of the same shape and surface properties (e.g., an ensemble of star-shaped rose quartz beads). A change to the shape and/or surface properties of all the beads in an ensemble resulted in a significant release from adaptation in PPA compared with conditions in which no ensemble feature changed. In contrast, in the object-sensitive lateral occipital area (LO), we only observed a significant release from adaptation when the shape of the ensemble elements varied, and found no significant results in additional scene-sensitive regions, namely, the retrosplenial complex and occipital place area. Together, these results demonstrate that the shape and surface properties of the individual objects comprising an ensemble both contribute significantly to object ensemble representation in anterior-medial ventral visual cortex and further demonstrate a functional dissociation between object- (LO) and scene selective (PPA) visual cortical regions and within the broader scene-processing network itself. PMID- 27676615 TI - Reduced Cognitive Control Demands after Practice of Saccade Tasks in a Trial Type Probability Manipulation. AB - Cognitive control is engaged to facilitate stimulus-response mappings for novel, complex tasks and supervise performance in unfamiliar, challenging contexts processes supported by pFC, ACC, and posterior parietal cortex. With repeated task practice, however, the appropriate task set can be selected in a more automatic fashion with less need for top-down cognitive control and weaker activation in these brain regions. One model system for investigating cognitive control is the ocular motor circuitry underlying saccade production, with basic prosaccade trials (look toward a stimulus) and complex antisaccade trials (look to the mirror image location) representing low and high levels of cognitive control, respectively. Previous studies have shown behavioral improvements on saccade tasks after practice with contradictory results regarding the direction of functional MRI BOLD signal change. The current study presented healthy young adults with prosaccade and antisaccade trials in five mixed blocks with varying probability of each trial type (0%, 25%, 50%, 75%, or 100% anti vs. pro) at baseline and posttest MRI sessions. Between the scans, participants practiced either the specific probability blocks used during testing or only a general 100% antisaccade block. Results indicated an overall reduction in BOLD activation within pFC, ACC, and posterior parietal cortex and across saccade circuitry for antisaccade trials. The specific practice group showed additional regions including ACC, insula, and thalamus with an activation decrease after practice, whereas the general practice group showed a little change from baseline in those clusters. These findings demonstrate that cognitive control regions recruited to support novel task behaviors were engaged less after practice, especially with exposure to mixed task contexts rather than a novel task in isolation. PMID- 27676617 TI - Why Effective Health Advocacy Is So Important Today. PMID- 27676616 TI - Repetition Enhancement of Amygdala and Visual Cortex Functional Connectivity Reflects Nonconscious Memory for Negative Visual Stimuli. AB - Most studies using a recognition memory paradigm examine the neural processes that support the ability to consciously recognize past events. However, there can also be nonconscious influences from the prior study episode that reflect repetition suppression effects-a reduction in the magnitude of activity for repeated presentations of stimuli-that are revealed by comparing neural activity associated with forgotten items to correctly rejected novel items. The present fMRI study examined the effect of emotional valence (positive vs. negative) on repetition suppression effects. Using a standard recognition memory task, 24 participants viewed line drawings of previously studied negative, positive, and neutral photos intermixed with novel line drawings. For each item, participants made an old-new recognition judgment and a sure-unsure confidence rating. Collapsed across valence, repetition suppression effects were found in ventral occipital-temporal cortex and frontal regions. Activity levels in the majority of these regions were not modulated by valence. However, repetition enhancement of the amygdala and ventral occipital-temporal cortex functional connectivity reflected nonconscious memory for negative items. In this study, valence had little effect on activation patterns but had a larger effect on functional connectivity patterns that were markers of nonconscious memory. Beyond memory and emotion, these findings are relevant to other cognitive and social neuroscientists that utilize fMRI repetition effects to investigate perception, attention, social cognition, and other forms of learning and memory. PMID- 27676619 TI - In Reply to Liaw and Westfall. PMID- 27676618 TI - Primary Care Research Should Be Done in Primary Care Settings. PMID- 27676620 TI - Clinician-Educator Track Career Advancement in Academic Medicine: Time to Update the Scoresheet. PMID- 27676621 TI - Principal Innovator: The Other PI. PMID- 27676622 TI - A New Era for the Morbidity and Mortality Conference: Aligning Tradition With Systems-Based Quality Improvement Efforts. PMID- 27676623 TI - Teaching Anatomy: It's Time for a Reality Check. PMID- 27676624 TI - Professionalism Sans Humanism: A Body Without A Soul. PMID- 27676625 TI - Powerless. PMID- 27676626 TI - Commentary on Photo of Eastern State Hospital, Knoxville, Tennessee. PMID- 27676627 TI - The Gold-Hope Tang, MD 2016 Humanism in Medicine Essay Contest: Third Place: Hand In-Hand. PMID- 27676629 TI - Identifying Multiple Potential Metabolic Cycles in Time-Series from Biolog Experiments. AB - Biolog Phenotype Microarray (PM) is a technology allowing simultaneous screening of the metabolic behaviour of bacteria under a large number of different conditions. Bacteria may often undergo several cycles of metabolic activity during a Biolog experiment. We introduce a novel algorithm to identify these metabolic cycles in PM experimental data, thus increasing the potential of PM technology in microbiology. Our method is based on a statistical decomposition of the time-series measurements into a set of growth models. We show that the method is robust to measurement noise and captures accurately the biologically relevant signals from the data. Our implementation is made freely available as a part of an R package for PM data analysis and can be found at www.helsinki.fi/bsg/software/Biolog_Decomposition. PMID- 27676628 TI - Artist's Statement: Diagnostic Dissonance. PMID- 27676630 TI - Association of life events and depressive symptoms among early postmenopausal Chinese women in Hong Kong. AB - OBJECTIVE: This study examined the occurrence of stressful life events (SLEs) and its association with the risk of developing depressive symptoms in midlife women. METHODS: A total of 518 Hong Kong Chinese postmenopausal women aged 50 to 64 years were recruited through random telephone dialing. Information on sociodemographic, health, and lifestyle variables was obtained through face-to face interviews at baseline, and at 3-year (T1) and 5-year (T2) follow-up. A Centre of Epidemiological Study Depression scale (CES-D) score >=16 was used to indicate high depressive symptoms. At T2, SLEs were assessed by a 21-item life event scale, adapted from the Holmes and Rahe Social Readjustment Rating Scale for Adults. Potential confounders were controlled for in the multivariable logistic regression analysis on the relation between SLEs and high depressive symptoms among 379 women without CES-D score >=16 at T1. RESULTS: 87.6% had experienced SLEs since T1 and 11.9% had CES-D score >=16 at T2. Compared with those without SLEs, women with one to three SLEs had 2.7-fold (95% CI, 0.6-12.1) increased risk of having CES-D score >=16, whereas those with four to nine SLEs had 5.2-fold (95% CI, 1.1-25.4) increased risk. A dose-response relationship was observed (P for trend = 0.005). Each additional SLEs experienced was associated with a 28% (95% CI, 1.07-1.54) increased risk of high depressive symptoms. CONCLUSIONS: Hong Kong Chinese women encounter many SLEs at midlife. Multiple episodes of SLE had a cumulative effect on the onset of depressive symptoms. Our findings have important implications for the identification and management of midlife women with high depressive symptoms. PMID- 27676631 TI - Trajectories of response to acupuncture for menopausal vasomotor symptoms: the Acupuncture in Menopause study. AB - OBJECTIVE: To examine the trajectories of responses to acupuncture treatment for menopausal vasomotor symptoms (VMS) and the characteristics of women in each trajectory. METHODS: Two hundred nine perimenopausal and postmenopausal women aged 45 to 60 years experiencing at least four VMS per day were recruited and randomized to receive up to 20 acupuncture treatments within 6 months or to a waitlist control group. The primary outcome was percent change from baseline in the mean daily VMS frequency. Finite mixture modeling was used to identify patterns of percent change in weekly VMS frequencies over the first 8 weeks. The Freeman-Holton test and analysis of variance were used to compare characteristics of women in different trajectories. RESULTS: Analyses revealed four distinct trajectories of change in VMS frequency by week 8 in the acupuncture group. A small group of women (11.6%, n = 19) had an 85% reduction in VMS. The largest group (47%, n = 79) reported a 47% reduction in VMS frequency, 37.3% (n = 65) of the sample showed only a 9.6% reduction in VMS frequency, and a very small group (4.1%, n = 7) had a 100% increase in VMS. Among women in the waitlist control group, 79.5% reported a 10% decrease in VMS frequency at week 8. Baseline number of VMS, number of acupuncture treatments in the first 8 weeks, and traditional Chinese medicine diagnosis were significantly related to trajectory group membership in the acupuncture group. CONCLUSIONS: Approximately half of the treated sample reported a decline in VMS frequency, but identifying clear predictors of clinical response to acupuncture treatment of menopausal VMS remains challenging. PMID- 27676632 TI - Duration of the menopausal transition is longer in women with young age at onset: the multiethnic Study of Women's Health Across the Nation. AB - OBJECTIVE: The menopausal transition (MT) is a critical period associated with physiologic changes that influence women's long-term health and longevity. Information is, however, limited regarding factors that influence age at the onset of the MT and its duration (ie, time from MT onset to the final menstrual period). METHODS: We analyzed data for 1,145 women from four sites of the Study of Women's Health Across the Nation who participated in the menstrual calendar substudy, had the start of the MT identified, and had no missing covariate information. Participants included from four racial/ethnic groups: African American, white, Chinese, and Japanese. Women completed daily menstrual calendars from 1996 to 2006 and questions on hormone therapy use monthly. Baseline measures included education, economic strain, and menstrual cycle characteristics. Annual measures included height, weight, and smoking status. Cox proportional hazards models were used to analyze the data. RESULTS: The adjusted median duration of the MT ranged from 4.37 years among the oldest age-at-onset quartile to 8.57 years among the youngest age-at-onset quartile (P < 0.001). Cigarette smoking was associated with an earlier onset (P < 0.001) and a shorter duration (P < 0.001). African American women had a longer duration (P = 0.012) than white women. Body mass index was associated with a later onset of the MT (P = 0.001) but not its duration. CONCLUSIONS: The duration of the MT was largely influenced by the age at which it began: earlier onset was associated with a longer transition. This finding provides a strong rationale for developing improved markers of the onset of the early MT. PMID- 27676633 TI - Relationship between equol producer status and metabolic parameters in 743 Japanese women: equol producer status is associated with antiatherosclerotic conditions in women around menopause and early postmenopause. AB - OBJECTIVE: Equol, an active metabolite possessing estrogen-like activity, is produced by the action of intestinal flora on soy isoflavones. There is an increasing evidence regarding its efficacy in the relief of menopausal symptoms, suppression of decreased bone mineral density, and lipid profile improvement. Only those with equol-producing capacity, however, seem to benefit. Thus, we examined the relationship between equol producer status and parameters associated with lifestyle-related diseases in women from their 20s to 80s. METHODS: This cross-sectional study was conducted among 743 women (21-89 y; average age: 52.5 +/- 11.8 y) who have undergone health screening at Tokyo Midtown Medical Center and given consent to participate in the study. The relationship between equol producer status and metabolic parameters was assessed. RESULTS: In our study, 236 women (32%) were equol producers. Equol producers had significantly lower triglycerides and higher high-density lipoprotein cholesterol levels compared with nonproducers. Equol-producing women in their 50s showed significantly lower body fat level, visceral fat area, triglyceride levels, pulse wave velocity, uric acid levels, and high sensitivity C-reactive protein levels. In addition, women in their 60s showed significantly higher levels of high-density lipoprotein cholesterol. In multivariate logistic regression, for women in their 50s, equol production was significantly associated with lower arterial stiffness and uric acid levels, and a high ratio of eicosapentaenoic acid to arachidonic acid, whereas it was significantly associated with lower urinary N-telopeptides in their 60s. CONCLUSIONS: Equol producer status was associated with favorable metabolic parameters, in women in the early phase postmenopause, with the transitional periods noted with declining intrinsic estrogen levels. PMID- 27676635 TI - Resistance training improves cardiovascular health in postmenopausal women. PMID- 27676634 TI - Dopaminergic contributions to working memory-related brain activation in postmenopausal women. AB - OBJECTIVE: The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. METHODS: Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed a functional magnetic resonance imaging visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. RESULTS: We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared with dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. CONCLUSIONS: Patterns of increased blood-oxygen-level dependent signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women to determine the effects of the increased brain activation on cognition and behavior. PMID- 27676636 TI - Long-term bisphosphonates: primum non nocere. PMID- 27676637 TI - Mechanisms explaining effects of pubertal timing on adulthood cardio-metabolic health. PMID- 27676639 TI - Intra-Operative Surgical Irrigation of the Surgical Incision: What Does the Future Hold-Saline, Antibiotic Agents, or Antiseptic Agents? AB - BACKGROUND: Intra-operative surgical site irrigation (lavage) is common practice in surgical procedures in general, with all disciplines advocating some form of irrigation before incision closure. This practice, however, has been neither standardized nor is there compelling evidence that it effectively reduces the risk of surgical site infection (SSI). This narrative review addresses the laboratory and clinical evidence that is available to support the practice of irrigation of the abdominal cavity and superficial/deep incisional tissues, using specific irrigation solutions at the end of an operative procedure to reduce the microbial burden at wound closure. METHODS: Review of PubMed and OVID for pertinent, scientific, and clinical publications in the English language was performed. RESULTS: Incision irrigation was found to afford a three-fold benefit: First, to hydrate the bed; second, to assist in allowing better examination of the area immediately before closure; and finally, by removing superficial and deep incisional contamination and lowering the bioburden, expedite the healing process. The clinical practice of intra-operative peritoneal lavage is highly variable and is dependent solely on surgeon preference. By contrast, intra operative irrigation after device-related procedures has become a standard of care for the prophylaxis of acute peri-prosthetic infection. The clinical evidence that supports the use of antibiotic irrigation is limited and based on retrospective analysis and few acceptable randomized controlled trials. The results of laboratory and animal studies using aqueous 0.05% chlorhexidine gluconate are favorable, suggesting that further studies are justified to determine its clinical efficacy. CONCLUSION: The adoption of appropriate and standardized intra-operative irrigation practices into peri-operative care bundles, which include other evidence-based strategies (weight-based antimicrobial prophylaxis, antimicrobial sutures, maintenance of normothermia, and glycemic control), offers an inexpensive and effective method to reduce the risk of post-operative SSI and deserves further evaluation. PMID- 27676638 TI - Menopausal symptoms and cardiovascular disease mortality in the Women's Ischemia Syndrome Evaluation (WISE). AB - OBJECTIVE: Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset. METHODS: The Women's Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning >=42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models. RESULTS: Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = -4.31, SE = 2.10, P = 0.04, multivariable). CONCLUSIONS: Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS. PMID- 27676641 TI - Capecitabine pharmacogenetics: historical milestones and progress toward clinical implementation. PMID- 27676642 TI - Important considerations in adolescent health maintenance: long-acting reversible contraception, human papillomavirus vaccination, and heavy menstrual bleeding. AB - PURPOSE OF REVIEW: The present article addresses recent research related to three key facets of adolescent preventive care and health maintenance: long-acting reversible contraception, human papillomavirus vaccination, and heavy menstrual bleeding. RECENT FINDINGS: Recent studies suggest that long-acting reversible contraception use results in significantly lower rates of unintended pregnancies, and is well tolerated by nulliparous adolescent females. Additionally, a strong recommendation from a pediatric primary care provider is extremely effective in ensuring human papillomavirus vaccination prior to sexual debut. Finally, heavy menstrual bleeding is often under-recognized in adolescents, and evaluation and treatment of these patients are variable. SUMMARY: Based on the recent literature findings, the pediatric primary care provider should be encouraged to, first, recommend long-acting reversible contraception for prevention of unintended pregnancy in adolescent patients; second, strongly endorse vaccination to protect against human papillomavirus in all patients prior to sexual debut; and, third, screen adolescent females for signs and symptoms of heavy menstrual bleeding. PMID- 27676643 TI - Electrospun Matrices for Pelvic Floor Repair: Effect of Fiber Diameter on Mechanical Properties and Cell Behavior. AB - Electrospun matrices are proposed as an alternative for polypropylene meshes in reconstructive pelvic surgery. Here, we investigated the effect of fiber diameter on (1) the mechanical properties of electrospun poly (lactic-co-glycolic acid) blended-poly(caprolactone) (PLGA/PCL) matrices; (2) cellular infiltration; and (3) the newly formed extracellular matrix (ECM) in vitro. We compared electrospun matrices with 1- and 8 MUm fiber diameter and used nonporous PLGA/PCL films as controls. The 8-MUm matrices were almost twice as stiff as the 1-MUm matrices with 1.38 and 0.66 MPa, respectively. Matrices had the same ultimate tensile strength, but with 80% the 1-MUm matrices were much more ductile than the 8-MUm ones (18%). Cells infiltrated deeper into the matrices with larger pores, but cellular activity was comparable on both substrates. New ECM was deposited faster on the electrospun samples, but after 2 and 4 weeks the amount of collagen was comparable with that on nonporous films. The ECM deposited on the 1-MUm matrices, and the nonporous film was about three times stiffer than the ECM found on the 8 MUm matrices. Cell behavior in terms of myofibroblastic differentiation and remodeling was similar on the 1-MUm matrices and nonporous films, in comparison to that on the 8-MUm matrices. We conclude that electrospinning enhances the integration of host cells as compared with a nonporous film of the same material. The 1-MUm matrices result in better mechanical behavior and qualitatively better matrix production than the 8-MUm matrices, but with limited cellular infiltration. These data are useful for designing electrospun matrices for the pelvic floor. PMID- 27676640 TI - Ethanol and High Cholesterol Diet Causes Severe Steatohepatitis and Early Liver Fibrosis in Mice. AB - BACKGROUND AND AIM: Because ethanol consumption is commonly associated with a high cholesterol diet, we examined whether combined consumption of ethanol and high cholesterol increases liver injury and fibrosis. METHODS: Male C57BL/6J mice were fed diets containing: 1) 35% of calories from corn oil (CTR), 2) CTR plus 0.5% (w/v) cholesterol (Chol), 3) CTR plus ethanol (27% of calories) (EtOH), or 4) EtOH+Chol for 3 months. RESULTS: In mice fed Chol or EtOH alone, ALT increased to ~160 U/L, moderate hepatic steatosis occurred, and leukocyte infiltration, necrosis, and apoptosis increased modestly, but no observable fibrosis developed. By contrast in mice fed EtOH+Chol, ALT increased to ~270 U/L, steatosis was more extensive and mostly macrovesicular, and expression of proinflammatory molecules (HMGB-1, TLR4, TNFalpha, ICAM-1) and leukocyte infiltration increased substantially. Necrosis and apoptosis also increased. Trichrome staining and second harmonic generation microscopy revealed hepatic fibrosis. Fibrosis was mostly sinusoidal and/or perivenular, but in some mice bridging fibrosis occurred. Expression of smooth muscle alpha-actin and TGF-beta1 increased slightly by Chol, moderately by EtOH, and markedly by EtOH+Chol. TGF-beta pseudoreceptor BAMBI increased slightly by Chol, remained unchanged by EtOH and decreased by EtOH+Chol. MicroRNA-33a, which enhances TGF-beta fibrotic effects, and phospho-Smad2/3, the down-stream signal of TGF-beta, also increased more greatly by EtOH+Chol than Chol or EtOH. Metalloproteinase-2 and -9 were decreased only by EtOH+Chol. CONCLUSION: High dietary cholesterol and chronic ethanol consumption synergistically increase liver injury, inflammation, and profibrotic responses and suppress antifibrotic responses, leading to severe steatohepatitis and early fibrosis in mice. PMID- 27676644 TI - Novel enzyme immunoassay system for simultaneous detection of six subclasses of antiphospholipid antibodies for differential diagnosis of antiphospholipid syndrome. AB - : Antiphospholipid syndrome, which often complicates systemic lupus erythematosus (SLE), features high occurrence of arterial and/or venous thrombosis and recurrent fetal loss. However, which antibody subclass contributes to which clinical event remains uncertain. We newly developed an up-to-date enzyme immunoassay system using the AcuStar automated analyzer (Instrumentation Laboratory, Bedford, Massachusetts, USA) for parallel detection of six subclasses of antiphospholipid antibodies (aPLs): anticardiolipin antibodies (aCL) of IgG, IgM, and IgA and anti-beta2-glycoprotein I antibodies (abeta2GPI) of IgG, IgM, and IgA. They were measured in 276 healthy volunteers and 138 patients with SLE: 45 with thromboembolic complications (29 arterial; 16 venous) and 93 without. Lupus anticoagulant activity in their plasma was measured according to the guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent Antibodies. aCL/beta2GPI was measured with a standard ELISA kit commonly used in Japan. The positive results of IgG aCL, IgA aCL, and IgG abeta2GPI were closely associated with thromboembolic complications, whereas IgM aCL and IgM abeta2GPI were not. receiver operating characteristic analysis revealed that the accuracy of predicting thromboembolic complications based on the composite test results of the former three antibodies were obviously higher than by each alone. Regarding agreement with the test results of lupus anticoagulant activity, IgG abeta2GPI showed the closest match. Patients with SLE frequently possess various combinations of the six aPL subclasses, and this antibody spectrum is closely associated with thromboembolic events in these patients. This new automated enzyme immunoassay system allows simultaneous analysis of the profile of aPL subclasses for the differential diagnosis of antiphospholipid antibody syndrome in its early stage. PMID- 27676645 TI - Fatal hemorrhage due to a spontaneous factor V inhibitor with lupus anticoagulant properties. AB - : Factor V inhibitors are rare and have varied clinical presentations. We report on a 76-year-old female admitted to the hospital for pneumonia and treated with multiple antibiotics. Her baseline prothrombin time was 15.6 s and the activated partial thromboplastin time was 35 s. On admission day 10, she developed arm weakness and brain imaging showed a subdural hematoma. The prothrombin time was now 59.1 s with an activated partial thromboplastin time of more than 160 s and a normal thrombin time. A mixing study did not correct the clotting times and coagulation factor assays showed a nonspecific inhibition pattern. Only factor V activity remained low with serial dilutions, however, and a 70 Bethesda Unit inhibitor was identified. Aggressive supportive care was initiated but the patient succumbed to the effects of the intracranial hemorrhage. Factor V inhibitors may display lupus anticoagulant properties and may cause catastrophic bleeding. Our case illustrates that these inhibitors can arise quickly and supports an association with antibiotics. PMID- 27676646 TI - Evidence of both von Willebrand factor deposition and factor V deposition onto AL amyloid as the cause of a severe bleeding diathesis. AB - : Acquired coagulopathies are common; uncommonly, adsorption of coagulation factors from the circulation into the tissues by pathologic amyloid exceeds the body's ability to produce factor and results in acquired factor deficiency. When amyloidosis does cause a coagulopathy, it is most often acquired factor X deficiency, but there are rare reports of amyloidosis being associated with other acquired factor deficiencies. We investigated a case of a severe bleeding diathesis, the cause of which was combined acquired factor V deficiency and concomitant acquired von Willebrand syndrome. Studies revealed prolonged prothrombin time and activated partial thromboplastin time. Mixing patient plasma with normal plasma corrected both the prothrombin time and activated partial thromboplastin time. Assays showed decreased factor V activity of 27%; Ristocetin cofactor activity was decreased at 49%, but von Willebrand antigen was elevated at 213%. Multimer analysis was consistent with type 2 von Willebrand syndrome. Lymph node biopsy documented amyloid light chain type (AL) amyloidosis; extraction of protein from the lymph node documented AL lambda light chain amyloid. Marrow biopsy documented IgG lambda myeloma. Immunohistochemical staining of the lymph node, using investigational polyvalent antibodies, demonstrated that both von Willebrand factor and factor V were identifiable in areas of amyloid deposition, providing evidence that these coagulation factors were adsorbed to the amyloid protein, resulting in accelerated clearance from the circulation, previously reported to be the mechanism of cases of acquired factor X deficiency in the setting of amyloidosis. Although there are case reports of acquired von Willebrand syndrome because of amyloidosis and case reports of acquired factor V deficiency because of amyloidosis, this appears to be the first reported case of concomitant acquired von Willebrand syndrome and acquired factor V deficiency because of amyloidosis, and the first report of localization of both von Willebrand protein and factor V protein to AL amyloid as a cause of a severe bleeding diathesis. PMID- 27676648 TI - Optical coherence tomography in drug-eluting stent restenosis: a technique in need of a strategy. AB - Owing to the overall increase in the use of DES, the number of patients presenting with DES restenosis is not insignificant in absolute terms. When DES restenosis occurs, it represents a challenging clinical entity in terms of classification and treatment. By providing near histology-level images, intravascular optical coherence tomography (OCT) has been used to describe vascular responses following PCI. Subsequently, OCT has been introduced to assess neointimal morphology and tissue characteristics of restenotic lesions to clarify the underlying pathophysiology. OCT imaging is best suited to reflect morphological characteristics of restenotic lesions, where its application enables to provide quantitative measures of neointimal growth and, more importantly, differentiate qualitative tissue properties amenable to specific treatment algorithms. Finally, morphological assessment of restenotic lesions might entail dedicated treatment strategies and accomplish individualized patient care. Whether the OCT-guided treatment of restenotic lesions might improve outcomes of this challenging clinical entity remains unanswered, since implementation and adequate treatment algorithms are matter of current debate. PMID- 27676647 TI - zWEDGI: Wounding and Entrapment Device for Imaging Live Zebrafish Larvae. AB - Zebrafish, an established model organism in developmental biology, is also a valuable tool for imaging wound healing in space and time with cellular resolution. However, long-term imaging of wound healing poses technical challenges as wound healing occurs over multiple temporal scales. The traditional strategy of larval encapsulation in agarose successfully limits sample movement but impedes larval development and tissue regrowth and is therefore not amenable to long-term imaging of wound healing. To overcome this challenge, we engineered a functionally compartmentalized device, the zebrafish Wounding and Entrapment Device for Growth and Imaging (zWEDGI), to orient larvae for high-resolution microscopy, including confocal and second harmonic generation (SHG), while allowing unrestrained tail development and regrowth. In this device, larval viability was maintained and tail regrowth was improved over embedding in agarose. The quality of tail fiber SHG images collected from larvae in the device was similar to fixed samples but provided the benefit of time lapse data collection. Furthermore, we show that this device was amenable to long-term (>24 h) confocal microscopy of the caudal fin. Finally, the zWEDGI was designed and fabricated using readily available techniques so that it can be easily modified for diverse experimental imaging protocols. PMID- 27676649 TI - Antihypertensive treatment and blood pressure control in patients with hypertension in daily clinical practice: a cross-sectional, multicenter, observational study in Egypt. AB - OBJECTIVE: Management of hypertension in Egypt is difficult because of various reasons. This real-life study was conducted to determine BP control rate, treatment modalities, factors influencing the choice of antihypertensive drugs, physicians' satisfaction with the treatment, and demographics of patients with uncontrolled BP who were treated for hypertension in daily clinical practice in Egypt. METHODS: This was a cross-sectional, multicenter, observational study conducted in patients treated for hypertension in out-patient private clinics in Egypt, during October 2011 to June 2012. RESULTS: Of 4139 patients with hypertension, 1509 (36.5%) had controlled BP and 2630 (63.5%) had uncontrolled BP. In BP controlled vs. uncontrolled groups, respectively, beta-blockers (41.7% vs. 41.0%) were the most frequently used antihypertensive agents, followed by diuretics (40% vs. 37.8%), angiotensin-converting enzyme inhibitors (35.3% vs. 34.9%), angiotensin receptor blockers (31.1% vs.19.4%), and calcium channel blockers (21.3% vs. 19.4%); the factors influencing the choice of antihypertensive therapy were "add-on therapy" (1.5% vs. 32.4%) and "change the current medication" (9.3% vs. 50.8%); physicians' satisfaction with treatment was rated as "excellent" (31.6% vs. 3.2%) and "poor" (1.6% vs. 58%). CONCLUSION: The majority of patients from Egypt had uncontrolled hypertension even after receiving treatment. This might increase awareness among physicians and enable them to prescribe appropriate treatment to patients with uncontrolled BP. Key limitations: The questionnaire used in the study for the evaluation of patient/physician satisfaction level was not standardized and was based on the choice and practice of the physicians. PMID- 27676651 TI - Rituximab in Membranous Nephropathy: Not All Studies Are Created Equal. AB - Many prospective studies and a recent randomized controlled trial have shown that the B-cell-depleting monoclonal antibody, rituximab, safely promotes the remission of nephrotic syndrome in approximately 65% of patients with membranous nephropathy (MN). Mechanistic studies have indicated that rituximab-induced proteinuria reduction is associated with clearance of anti-podocyte antigens phospholipase 2 receptor autoantibodies and subepithelial immune complexes, the hallmarks of the disease. A recently published study reported results which, at first sight, looked less favorable and implied that, due to a publication bias against negative results, the efficacy of rituximab in MN might be overestimated. Since patients received only one or 2 rituximab administrations, the authors suggest that when rituximab is used, higher doses and longer treatments should be considered. In this study, we highlight limitations of the study and warn against an oversimplified interpretation of the data. Though information on the optimal dose of rituximab to use in MN is still limited, available data from studies with predefined rituximab administration protocols collectively support the concept of titrating rituximab to the number of circulating B-cells that are invariably depleted after the first or second administration. Additional doses may increase the risk of adverse effects and related costs without augmenting efficacy. Importantly, underpowered studies with inconclusive results should not be confused with negative studies formally proving a neutral effect of a treatment. Until data from ad hoc designed clinical trials are available, the B-cell-driven protocol should be the preferred regimen, since it is similarly effective, but safer and more cost effective than other protocols employing multiple rituximab administrations. PMID- 27676652 TI - Magnetic resonance imaging evaluation of endolymphatic hydrops andpost-operative findings in cases with otosclerosis. AB - CONCLUSIONS: The presence of endolymphatic hydrops (EH) in the vestibule on magnetic resonance imaging (MRI) might be a high-risk factor for complications in cases that are candidates for stapes surgery. OBJECTIVE: Pre-operative detection of EH could be valuable in cases that are candidates for stapes surgery to prevent unpredictable complications following surgery. Pre-operative MRI findings and post-operative findings following stapes surgery were compared to evaluate the efficacy of such MRI evaluation for the management of cases with otosclerosis. SUBJECTS AND METHODS: Sixteen cases who underwent pre-operative evaluation by 3T MRI performed 4 h after intravenous injection of gadolinium and stapes surgery for otosclerosis were recruited. Imaging data concerning the degree of EH in the vestibule and cochlea were compared with post-operative clinical findings for all cases. RESULTS: Mild EH in the cochlea or the vestibule was observed in eight ears and one ear, respectively, whereas one ear showed significant EH both in the cochlea and the vestibule. The post-operative course was uneventful in 12 of 14 cases with no EH in the vestibule, and the other two cases had a short period of dizziness, but two cases with EH in the vestibule had a long period of dizziness. PMID- 27676653 TI - A Novel Role for Flotillin-Containing Lipid Rafts in Negative-Feedback Regulation of Thyroid-Specific Gene Expression by Thyroglobulin. AB - BACKGROUND: Thyroglobulin (Tg) stored in thyroid follicles regulates follicular function in thyroid hormone (TH) synthesis by suppressing thyroid-specific gene expression in a concentration-dependent manner. Thus, Tg is an intrinsic negative feedback regulator that can restrain the effect of thyrotropin (TSH) in the follicle. However, the underlying mechanisms by which Tg exerts its prominent autoregulatory effect following recognition by thyrocytes remains unclear. METHODS: In order to identify potential proteins that recognize and interact with Tg, mass spectrometry was used to analyze immunoprecipitated Tg-bound proteins derived from Tg-treated rat thyroid FRTL-5 cells. RESULTS: Flotillin 1 and flotillin 2, two homologs that are integral membrane proteins in lipid rafts, were identified as novel Tg-binding proteins with high confidence. Further studies revealed that flotillins physically interact with endocytosed Tg, and together these proteins redistribute from the cell membrane to cytoplasmic vesicles. Treatment with the lipid raft disrupter methyl-beta-cyclodextrin abolished both the endocytosis and the negative-feedback effect of Tg on thyroid specific gene expression. Meanwhile, siRNA-mediated knockdown of flotillin 1 or flotillin 2 also significantly inhibited Tg effects on gene expression. CONCLUSION: Together these results indicate that flotillin-containing lipid rafts are essential for follicular Tg to be recognized by thyrocytes and exert its negative-feedback effects in the thyroid. PMID- 27676655 TI - Mortal remains, immortal work. PMID- 27676654 TI - Transumbilical Single-Incision Laparoscopic Surgery in Children with Conventional Instruments: Our Early Experience. AB - OBJECTIVE: Laparoscopic surgery is the current accepted approach in most pediatric surgical centers. In an attempt to further minimize the surgical trauma and improve cosmetic outcome, new techniques with a single incision through the umbilicus have been proposed and we believe they will become the standard choices for pediatric surgery. This report describes our initial experience with transumbilical single-incision laparoscopic surgery (TSILS) in children with conventional instruments. MATERIALS AND METHODS: A retrospective review of 82 pediatric patients who underwent TSILS in children with conventional instruments from January 2011 to June 2015 was performed. The operations included 56 appendectomies, 9 cholecystectomies, and 17 spermatic vein ligations. RESULTS: The average age by procedure was 6.2 years for appendectomy (range of 3-14 years); 12.4 years for cholecystectomy (range of 10-14 years); and 12.8 years for spermatic vein ligation (range of 11-14 years). The average operative time was 32 minutes for appendectomy (range of 25-56 minutes); 54 minutes for cholecystectomy (range of 35-95 minutes); and 23 minutes for spermatic vein ligation (range of 17 41 minutes). The average length of staying in hospital was 3 days (range of 2-5 days). All of the operations in 82 cases were successful. None required conversion to open or conventional laparoscopic surgery. There was no obvious wound pain. In addition, there were no wound infections on umbilicus and any other intraoperative complications. There was no obvious scar at patients' umbilicus after postoperative follow-up for 2-4 weeks. CONCLUSIONS: TSILS is a safe and viable technique that may be used successfully in pediatric surgery. Additionally, excellent cosmetic results are obtained as evidenced by imperceptible umbilical scarring. PMID- 27676656 TI - Doctors in fiction: the medical profession through authors' eyes. PMID- 27676658 TI - Expression of peropsin in human skin is related to phototransduction of violet light in keratinocytes. PMID- 27676657 TI - A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication. AB - The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking alpha7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension. PMID- 27676659 TI - Effect of Vitamin D Supplementation on Pain: A Systematic Review and Meta analysis. AB - BACKGROUND: There is conflicting evidence from previous qualitative reviews on the effect of vitamin D supplementation on pain. OBJECTIVE: To determine with quantitative methods if vitamin D supplementation lowers pain levels. STUDY DESIGN: Quantitative meta-analysis of published randomized controlled trials (RCTs). SETTING: This meta-analysis examined all studies involving the effect of vitamin D supplementation on pain score. METHOD: Electronic sources (Medline, Embase, Cochrane Central Register of Controlled Trials, clinical trials website, and Google scholar) were systematically searched for RCTs of vitamin D supplementation and pain from inception of each database to October 2015. RESULTS: Nineteen RCTs with 3,436 participants (1,780 on vitamin D supplementation and 1,656 on placebo) were included in the meta-analysis. For the primary outcome (mean change in pain score from baseline to final follow-up), 8 trials with 1,222 participants on vitamin D and 1,235 on placebo reported a significantly greater mean decrease in pain score for the vitamin D group compared to placebo (mean difference -0.57, 95% CI: -1.00 to -0.15, P = 0.007). The effect from vitamin D was greater in patients recruited with pre-existing pain (P-value for interaction = 0.03). Fourteen studies (1,548 on vitamin D, 1,430 on placebo) reported the mean pain score at final follow-up outcome, and no statistical difference was observed (mean difference -0.06, 95%CI: -0.44 to 0.33, P = 0.78). In 4 studies which reported pain improvement (209 on vitamin D, 146 on placebo), the effect size although not significant, shows participants in the vitamin D supplementation group were more likely to report pain improvement compared with the placebo group (relative risk 1.38, 95%CI: 0.93 to 2.05, P = 0.11). LIMITATIONS: Only a few studies reported the mean score change from baseline to final follow-up, and we do not have enough data to determine any modifying effect of baseline vitamin D status and different doses of vitamin D supplementation on pain. CONCLUSION: A significantly greater mean decrease in pain score (primary outcome) was observed with vitamin D supplementation compared with placebo in people with chronic pain. These results suggest that vitamin D supplementation could have a role in the management of chronic pain. KEY WORDS: Meta-analysis, pain, randomized controlled trials, vitamin D supplementation. PMID- 27676660 TI - Treatment of Neuropathic Pain Using Pulsed Radiofrequency: A Meta-analysis. AB - BACKGROUND: Neuropathic pain (NP) is a major public health problem worldwide. Because of the unclear mechanism of NP, its treatment is one of the most difficult medical problems. As a targeted, noninvasive, safe therapy, pulsed radiofrequency (PRF) provides a new method for the treatment of NP; however, its effect on this treatment still lacks support from evidence-based medicine. OBJECTIVE: To conduct a meta-analysis of available randomized controlled trials and to evaluate the effectiveness and clinical utility of PRF for the treatment of NP. STUDY DESIGN: Meta-analysis. SETTING: All selected studies were randomized controlled trials. METHOD: A systematic and comprehensive database search was performed of the PubMed, CENTRAL, EMBASE.com, Cochrane Library, Chinese Biomedical Literature, and Wanfang databases for literature published from the establishment of the databases to December 19, 2015. According to inclusion and exclusion criteria, the results of randomized controlled trials supporting PRF for NP treatment were collected. The risk of bias tool described in the Cochrane Handbook version 5.1.0 was used to assess the quality of each trial. Meta analysis was performed using RevMan 5.3 software. RESULTS: A total of 12 randomized controlled trials involving 592 patients met the inclusion criteria. Overall, the results of the meta-analysis showed that, compared with the control group, PRF had a better effect on postherpetic neuralgia (PHN) in terms of pain score (one week, one month, and 3 months), excellent and good rate (one day, one month), and efficiency rate (one day). But PRF did not have a better effect on radicular pain in pain score (3 months). Side effects were less frequently found with the PRF treatment. LIMITATIONS: Although we repeatedly tested the key words and used a manual method to prevent the loss of studies, due to the limitation of the included studies, some of the data were insufficient to complete the meta analysis, and we were unable to obtain the original data from some studies. Some studies did not report the blind design, which decreased the quality of the current study. CONCLUSION: PRF did not have a better effect on radicular pain, and PRF is an effective and safe therapeutic alternative for the analgesia of PHN. However, for a high recurrence rate over a long period, repeated PRF treatment has limitations. KEY WORDS: Neuropathic pain, pulsed radiofrequency, analgesia, meta-analysis. PMID- 27676661 TI - Comparative Effectiveness of Suprascapular Nerve Block in the Relief of Acute Post-Operative Shoulder Pain: A Systematic Review and Meta-analysis. AB - BACKGROUND: The suprascapular nerve accounts for 70% of shoulder sensory innervations, and suprascapular nerve block (SSNB) has been shown to be effective in the relief of chronic shoulder pain including rotator cuff tendinitis, subdeltoid impingement syndrome, and adhesive capsulitis. However, this remains inconclusive for patients undergoing surgery. The present meta-analysis aimed to explore the effectiveness of SSNB for relieving acute post-operative shoulder pain. OBJECTIVE: To explore the effectiveness of SSNB for relieving acute post operative shoulder pain. STUDY DESIGN: A systematic review and meta-analysis. SETTING: Services of general surgery, orthopaedics, and anaesthesiology. METHODS: A systematic search of studies on SSNB for post-operative shoulder pain was conducted mainly in PubMed and Scopus. The standardized mean difference (SMD) of post-operative pain scales of SSNB versus placebo was treated as the primary outcome, whereas the odds ratio of nausea of SSNB versus placebo comprised the secondary outcome. RESULTS: The meta-analysis included 7 randomized controlled trials and 2 comparative studies comprising 681 participants in total. The quantitative analysis showed a significantly lower pain level of SSNB versus placebo in the shoulder surgery patient group (SMD: -0.33; 95% confidence level [CI]: -0.51 to -0.15), but not in the non-shoulder surgery group (SMD: 0.28; 95% CI: -0.37 to 1.93). The pooled odds ratio of nausea in the SSNB arm compared with the placebo arm was 0.20 (95% CI: 0.09 to 0.45), indicating a reduction in the incidence of nausea following SSNB. LIMITATIONS: Heterogeneity of included trials. CONCLUSIONS: SSNB significantly reduced acute post-operative shoulder pain in the shoulder surgery group but not in patients undergoing laparoscopic surgery or thoracotomy. This suggests that SSNB can be used as a method of polymodal analgesia for patients undergoing shoulder surgery; however, it is not recommended for the non-shoulder surgery patient population. KEY WORDS: Suprascapular nerve, shoulder surgery, thoracotomy, laparoscopic surgery. PMID- 27676662 TI - Calcitonin as an Additive to Local Anesthetic and Steroid Injection Using a Modified Coronoid Approach in Trigeminal Neuralgia. AB - BACKGROUND: Pharmacotherapy is the main treatment for management of trigeminal neuralgia. However, many patients become refractory to drugs. OBJECTIVES: The present study aimed to evaluate the effect of adding calcitonin to local anesthetic and methylprednisolone using a modified coronoid approach in management of trigeminal neuralgia pain involving the mandibular and/or maxillary branches. STUDY DESIGN: Randomized double blind clinical trial. SETTING: Hospital outpatient setting. METHODS: Thirty-three patients received maxillary and mandibular blocks by a modified coronoid approach. Patients were allocated into 2 groups. Group 1 received a block with 3 mL of lidocaine 0.5% plus 40 mg of methylprednisolone and another syringe contained 1 mL of 0.9% saline. Group 2 received a block with 3 mL of lidocaine 0.5% plus 40 mg of methylprednisolone and another syringe contained 50 international units of calcitonin. Pain was evaluated by visual analog scale (VAS) before the block (basal), at 2 weeks, one month after the procedure, and monthly for one year. Duration of the effective pain relief of the first block (VAS = 3) was reported. Repeated blockade was allowed for any patient reporting a VAS > 30 mm during one year of follow-up and the number of blocks were reported. Adverse effects were also reported. RESULTS: A significantly longer duration of effective pain relief was noticed in group 2 compared with group 1 (P < 0.0004) while the duration of effective pain relief of the second block in group 1 was 28.5 +/- 8.9 weeks. Four patients did not need repeated blocks in group 1 versus 15 in group 2. Six patients received 2 blocks versus 2 patients in each group, respectively. Moreover, 6 patients needed 3 blocks in group1 versus none in group 2. No serious adverse events were reported during or after the interventional procedure. VAS was comparable in both groups (P > 0.05). LIMITATIONS: Small sample size. CONCLUSION: Calcitonin may be a useful additive to local anesthetic and steroid in management of trigeminal neuralgia. Also, a modified coronoid approach for maxillary and mandibular nerve is simple, free of radiation, safe, and may be an effective percutaneous procedure in trigeminal neuralgia. KEY WORDS: Calcitonine, modifed, coronoid approach, trigeminal neuralgia. PMID- 27676663 TI - Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain. AB - BACKGROUND: Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). OBJECTIVE: To assess the antinociceptive effect of TSN IIA on CIBP. STUDY DESIGN: A randomized, double-blind, controlled animal trial was performed. SETTING: University lab in China. METHODS: A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. RESULTS: TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. LIMITATIONS: Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. CONCLUSIONS: Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. KEY WORDS: Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain, breakthrough pain. PMID- 27676664 TI - Pulsed Dose Radiofrequency Before Ablation of Medial Branch of the Lumbar Dorsal Ramus for Zygapophyseal Joint Pain Reduces Post-procedural Pain. AB - BACKGROUND: One of the potential side effects with radiofrequency ablation (RFA) includes painful cutaneous dysesthesias and increased pain due to neuritis or neurogenic inflammation. This pain may require the prescription of opioids or non opioid analgesics to control post-procedural pain and discomfort. OBJECTIVES: The goal of this study is to compare post-procedural pain scores and post-procedural oral analgesic use in patients receiving continuous thermal radiofrequency ablation versus patients receiving pulsed dose radiofrequency immediately followed by continuous thermal radiofrequency ablation for zygopophaseal joint disease. STUDY DESIGN: This is a prospective, double-blinded, randomized, controlled trial. Patients who met all the inclusion criteria and were not subject to any of the exclusion criteria were required to have two positive diagnostic medial branch blocks prior to undergoing randomization, intervention, and analysis. SETTING: University hospital. METHODS: Eligible patients were randomized in a 1:1 ratio to either receive thermal radiofrequency ablation alone (standard group) or pulsed dose radiofrequency (PDRF) immediately followed by thermal radiofrequency ablation (investigational group), all of which were performed by a single Board Certified Pain Medicine physician. Post-procedural pain levels between the two groups were assessed using the numerical pain Scale (NPS), and patients were contacted by phone on post-procedural days 1 and 2 in the morning and afternoon regarding the amount of oral analgesic medications used in the first 48 hours following the procedure. RESULTS: Patients who received pulsed dose radiofrequency followed by continuous radiofrequency neurotomy reported statistically significantly lower post-procedural pain scores in the first 24 hours compared to patients who received thermal radiofrequency neurotomy alone. These patients also used less oral analgesic medication in the post procedural period. LIMITATIONS: These interventions were carried out by one board accredited pain physician at one center. The procedures were exclusively performed using one model of radiofrequency generator, at one setting for the PDRF and RFA. The difference in the number of levels of ablation was not considered in the analysis of the results. CONCLUSION: Treating patients with pulsed dose radiofrequency prior to continuous thermal radiofrequency ablation can provide patients with less post-procedural pain during the first 24 hours and also reduce analgesic requirements. Furthermore, the addition of PDRF to standard thermal RFA did not prolong the time of standard thermal radiofrequency ablation procedures, as it was performed during the typically allotted time for local anesthetic action. KEY WORDS: Low back pain, facet joint disease, medial branch block, Radiofrequency ablation, thermal radiofrequency, pulsed dose radiofrequency, PDRF, zygapophyseal joint. PMID- 27676665 TI - Efficacy and Safety of Ketamine Added to Local Anesthetic in Modified Pectoral Block for Management of Postoperative Pain in Patients Undergoing Modified Radical Mastectomy. AB - BACKGROUND: Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain. Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries. OBJECTIVES: This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery. STUDY DESIGN: A randomized, double-blind, prospective study. SETTING: Academic medical center. METHODS: This study is registered at www.clinicaltrials.gov under number: (NCT02620371) after approval by the ethics committee of South Egypt Cancer Institute, Assuit University, Assuit, Egypt. Sixty patients aged 18 - 60 years scheduled for modified radical mastectomy were enrolled and randomly assigned into 2 groups (30 patients each): Control group patients were given ultrasound guided, Pecs block with 30 mL of 0.25% bupivacaine only. Ketamine group patients were given ultrasound-guided, Pecs block with 30 mL of 0.25% bupivacaine plus ketamine hydrochloride (1 mg/kg). Patients were followed up for 48 hours postoperatively for vital signs, VAS score, first request of rescue analgesia and total morphine consumption, sedation score, and side effects. RESULTS: Ketamine plus bupivacaine in Pecs block compared to bupivacaine alone prolonged the mean time of first request of analgesia (18.25 +/- 1.98), (12.56 +/- 2.64), respectively (P < 0.001), reduced total morphine consumption (12.50 +/- 4.63), (18.86 +/- 6.28), respectively (P = 0.016). With no significant difference in hemodynamics, respiratory rate, oxygen saturation, VAS and sedation scores, and side effects observed between the 2 groups (P > 0.05). LIMITATIONS: This study is limited by its sample size. CONCLUSION: The addition of ketamine to modified Pecs block prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy. KEY WORDS: Ketamine, bupivacaine, pecs block, postoperative, pain, breast cancer. PMID- 27676666 TI - Percutaneous Kyphoplasty Evaluated by Cement Volume and Distribution: An Analysis of Clinical Data. AB - BACKGROUND: Percutaneous kyphoplasty (PKP) could achieve rapid pain relief for older patients with osteoporotic vertebral compression fractures (OVCFs). Bone cement in PKP was the key factor keeping the stabilization of the vertebral body. However, the same amount of cement can distribute differently in a vertebral body and can thereby result in different surgery outcomes. Therefore, the volume and distribution of bone cement should be considered as 2 distinct variables to evaluate the effectiveness of PKP. OBJECTIVES: On the basis of comparing surgery outcomes between patients with different recovery states measured by visual analog scores (VAS) and exploring the relationships among bone cement, surgery outcomes, and degrees of pain relief, the objective of the study is to determine the best combination of cement volume and cement distribution for PKP. STUDY DESIGN: Retrospective study. METHODS: There were 220 patients with 220 vertebra who received PKP in our hospital from January 2011 to January 2013. According to the different pain relief degrees, patients were divided into 2 groups. The epidemiological data, surgical outcomes, and complications were compared between the 2 groups. A receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of bone cement on patient recovery state. A correlation analysis was used to analyze the relationships between bone cement and surgery outcomes. Moreover, logistic regression was also used to assess the safety of cement injection. RESULTS: There were 77 recuperators and 143 non-recuperators in our study. There were no differences in epidemiological data between the 2 groups. However, the surgery duration, cement volume, cement distribution, restoration rate of vertebral height, and improvement of kyphotic angle in the recuperator group were all higher than those in the non-recuperator group. The area under the ROC curve of cement distribution as a predictor of pain relief was better than that of cement volume (0.77 vs. 0.65, P < 0.05). Cement distribution had a sensitivity of 62% and a specificity of 84% when it was at 0.49. Cement volume had a sensitivity of 49% and a specificity of 82% when it was at 3.80 mL. All patients were then divided into 4 parts based on the 2 values. Extensive cement distribution (more than or equal to 0.49) was discovered to noticeably increase the recuperative rate both for a small cement volume (less than 3.80 mL) and a large cement volume (more than or equal to 3.80 mL). A small cement volume with an extensive distribution had the same recuperative effect as a large cement volume with a confined distribution (x2 = 2.880, P = 0.090). When the cement volume was constant, cement distribution was positively correlated with the restoration rate of vertebral height and improvement of the kyphotic angle (r2 = 0.207, P < 0.01; r2 = 0.159, P = 0.02), but cement distribution was not a risk factor for cement leakage or adjacent vertebral fractures (OR = 35.760, 95%CI: 0.096 - 13291.207, P > 0.05; OR = 0.051, 95% CI: 0.011 - 1.032, P > 0.05). Although a large cement volume may contribute to the restoration of vertebral height (r2 = 0.153, P < 0.05), it was found to be a risk factor for adjacent vertebral fractures (OR = 1.733, 95% CI: 1.158 - 2.595, P < 0.05). LIMITATIONS: The distribution of cement in fractured vertebra was not calcuated accurately. CONCLUSIONS: The diagnostic value of cement distribution is better than that for cement volume in relieving patient pain. A cement distribution above 0.49 with a small cement volume should be suggested for PKP. An extensive cement distribution can improve the kyphotic angle and vertebral height effectively, and it does not cause cement leakage or adjacent vertebral fractures. KEY WORDS: Psteoporotic vertebral compression fractures percutaneous kyphoplasty cement volume cement distribution. PMID- 27676668 TI - In errata: Novel Single Puncture Approach for Simplicity In errata: In Response to Letter to the Editor: Use of High Volume Injectate. PMID- 27676667 TI - Subtle Sensory Abnormalities Detected by Quantitative Sensory Testing in Patients with Trigeminal Neuralgia. AB - BACKGROUND: Trigeminal neuralgia (TN) is characterized by paroxysmal pain attacks affecting the somatosensory distributions of the trigeminal nerve. It is thought to be associated with a neurovascular conflict most frequently, but pathomechanisms have not been fully elucidated. In general, no sensory deficit is found in routine clinical examination. There is limited data available, however, showing subtle subclinical sensory deficits upon extensive testing. OBJECTIVE: We used quantitative sensory testing (QST) to detect abnormalities in sensory processing in patients with TN by comparing the affected and non-affected nerve branches with their contralateral counterparts and by comparing the results of the patients with those of controls. STUDY DESIGN: Observational study. SETTING: University Hospital, Departments of Neurosurgery, Institute for Cognitive and Clinical Neuroscience. METHODS: QST was conducted on 48 patients with idiopathic TN and 27 controls matched for age and gender using the standardized protocol of the German Neuropathic Pain Network. Stimulations were performed bilaterally in the distribution of the trigeminal branches. The patients had no prior invasive treatment, and medications at the time of examination were noted. RESULTS: In patients with TN deficits in warm and cold sensory detection thresholds in the affected and also the non-affected nerve branches were found. Tactile sensation thresholds were elevated in the involved nerve branches compared to the contralateral side. LIMITATIONS: More data are needed on the correlation of such findings with the length of history of TN and with changes of the morphology of the trigeminal nerve. CONCLUSIONS: QST shows subtle sensory abnormalities in patients with TN despite not being detected in routine clinical examination. Our data may provide a basis for further research on the development of TN and also on improvement after treatment. KEY WORDS: Quantitative sensory testing, trigeminal neuralgia, facial pain, neuropathic pain, microvascular decompression, cranial nerve. PMID- 27676669 TI - Comparison of the Effects of Epidural Anesthesia and Local Anesthesia in Lumbar Transforaminal Endoscopic Surgery. AB - BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) is a standard technique for the treatment of lumbar disc hernia. Thus far, most surgeons have recommended local anesthesia. However, in clinical practice, some patients experience pain and are unable to cooperate with the surgery during intervertebral foramen hemp expansion. The use of general anesthesia may create a greater risk of complications because of nerve root anomalies; thus, intraoperative neurophysiological monitoring should be utilized. Reports regarding the use of epidural anesthesia are few in comparison. OBJECTIVE: To investigate the risks and contingency plans of epidural anesthesia in lumbar transforaminal endoscopic surgery. STUDY DESIGN: A retrospective analysis of all lumbar transforaminal endoscopic surgeries performed from 2010 to 2014. SETTING: Kanghua hospital. METHODS: Patients treated with local and epidural anesthesia were divided into 2 groups. In local anesthesia group (A) and local anesthesia group (B), 0.5% lidocaine and 0.25% ropivacaine was administered, respectively. The incidences of complications, including urological complications, in each surgical group as well as Oswestry disability idex (ODI) improvement rates, postoperative patient satisfaction rates, and x-ray exposure times were assessed.
RESULTS: From 2010 to 2014, there were 286 cases of lumbar transforaminal endoscopic surgeries, 121 cases utilizing local anesthesia and 165 cases utilizing epidural anesthesia. In cases in which neurological complications occurred after surgery, 15 cases involved nerve root numbness, including one case of foot drop and 2 cases of cerebrospinal leakage in the local anesthesia group, which accounted for 12.4% of group A. However, in the epidural anesthesia group, which accounted for 9.70% of group B, there were 16 cases of nerve root numbness, including 2 cases of foot drop and 2 cases of cerebrospinal leakage. No significant difference was detected in the incidence of neurological complications between the 2 groups (P > 0.05). The ODI improvement rates were 86.0% in the local anesthesia group and 85.4% in the epidural anesthesia group (P > 0.05). The average x-ray exposure times were 14.7 seconds and 16 seconds in the local anesthesia group and epidural anesthesia group, respectively (P > 0.05). The postoperative patient satisfaction rates were 73.6% and 91% in the local anesthesia group and epidural anesthesia group, respectively (P < 0.001). LIMITATIONS: This was a single-blind study, and the complications observed were related to the learning curve; all these factors may lead to biases. CONCLUSIONS: Epidural anesthesia in transforaminal lumbar surgery is feasible and safe, and no significant difference in neurological complications was observed between the epidural anesthesia and the local anesthesia groups. However, for the patients concerned, the postoperative patient satisfaction rate was significantly greater in the epidural anesthesia group. It is noteworthy that the x-ray exposure times of the groups were not significantly different. KEY WORDS: Epidural anesthesia, transforaminal lumbar surgery, neurological complications, cerebrospinal leak. PMID- 27676670 TI - Occipital Neuromodulation: A Surgical Technique with Reduced Complications. AB - BACKGROUND: Occipital neuromodulation is a promising treatment modality for refractory headache, but lead migration remains a frequent surgical complication. OBJECTIVES: The primary objective was to identify surgical techniques that may minimize adverse events, particularly lead migration. We hypothesized that a surgical technique employing 2-point anchoring of stimulator leads designed to provide a tension-relief loop and the use of ultrasound for lead placement would decrease the complication rate. STUDY DESIGN AND SETTING: A retrospective analysis was performed through electronic medical record chart review in a tertiary referral center. METHODS: Institutional Review Board (IRB) approval was obtained. Eighteen patients had a trial and subsequent permanent occipital nerve stimulator (ONS) implantation between 2004 and 2011 and were included. Adverse events were recorded and efficacy outcome variables analyzed for significance. RESULTS: The cohort was a median (IQR) 45 (37 - 58) in age and 9 (50%) were women. Tension-relief loops placed via a 2-point anchoring technique and ultrasound use for occipital lead placement were evident in 16 (89%) and 13 (72%), respectively. There was one (6%) clinically insignificant lead position change, not definitively a lead migration, which could have been an artifact of fluoroscope positioning. Adverse events included one (6%) battery malfunction, one (6%) lead malfunction, and 2 (12%) post-implantation infections. Following ONS, there were significant reductions in numeric rating scale (NRS) pain scores from a median (IQR) of 9.5 (8.25 - 10) to 2.5 (1 - 4.75) (P < 0.0001), headache days per week from 7 (7 - 7) to 1.5 (0.375 - 1.75) (P = 0.0005), and the number of daily headache medication from 3 (2.25 - 4) to 2.5 (2 - 3.75) (P = 0.0112). LIMITATIONS: Limitations include retrospective study design, investigator bias, and non-standardized intervals of headache burden assessment. CONCLUSIONS: In ONS, utilization of a 2-point anchoring technique with a tension-relief loop may significantly minimize the risk of lead migration, based on the absence of definitive lead migration in our series. Ultrasound use may improve the anatomic accuracy of lead placement with the possibility of improved efficacy. ONS was associated with significantly decreased headache pain, frequency, and medication use. KEY WORDS: Occipital neuromodulation, occipital nerve stimulation, surgical technique, lead migration, tension-relief loop. PMID- 27676671 TI - Fluoroscopically Guided Thoracic Interlaminar Epidural Injection: A Comparative Epidurography Study Using 2.5 mL and 5 mL of Contrast Dye. AB - BACKGROUND: Thoracic epidural anesthesia (TEA) is frequently used to maintain intraoperative analgesia. After injecting the initial bolus dose of epidural local anesthetics (LA), intermittent injection of LA through an epidural catheter is required to maintain the intraoperative analgesia. For intermittent epidural administration, usually 2 - 5 mL of LA has been used. However, no studies have suggested an optimal volume of LA of TEA for intermittent epidural administration of TEA. OBJECTIVE: We focused on identifying an optimal volume of LA of TEA using epidurography of the thoracic level with 2 different volumes of contrast dye. STUDY DESIGN: Prospective, randomized study. SETTING: An interventional pain management practice in South Korea. METHODS: After Institutional Review Board approval, 70 patients undergoing thoracic epidural catheterization for upper abdominal and thoracic surgery were randomly assigned to one of the 2 contrast dye volume groups of 35 patients each (A, 2.5 mL and B, 5.0 mL). Epidurography was evaluated to confirm how many spinal segments were covered by contrast dye. The spreads in the cephalad and caudad directions were also evaluated. RESULTS: The total number of vertebral segments evaluated by contrast dye were 7.5 +/- 2.0, and 8.4 +/- 2.6, respectively in groups A and B. The number of patients who showed contrast dye spread of more than 5 vertebral segments was 34/35 (97%) in both groups. Group B resulted in higher contrast dye distribution in the cephalad direction compared to group A (T2.6 vs. T3.6 ). LIMITATIONS: We used a test dose of contrast dye to confirm the contrast was in epidural space, not intrathecal or vascular, before injection of the main dose of contrast dye. The present study did not include the volume of test dose. CONCLUSION: The volume of 2.5 mL for intermittent epidural administration would be enough for the analgesic effect of upper abdominal and thoracic surgery while avoiding excessive upper thoracic and cervical spread. KEY WORDS: Thoracic epidural anesthesia, intermittent epidural administration, optimal volume, epidurography, cephalad, caudad, analgesic effect. PMID- 27676672 TI - Outcome of Percutaneous Lumbar Synovial Cyst Rupture in Patients with Lumbar Radiculopathy. AB - BACKGROUND: Lumbar synovial cysts can result from spondylosis of facet joints. These cysts can encroach on adjacent nerve roots, causing symptoms of radiculopathy. Currently the only definitive treatment for these symptoms is surgery, which may involve laminectomy or laminotomy, with or without spinal fusion. Surgery has been reported to successfully relieve radicular pain in 83.5% of patients by Zhenbo et al. Little information is available concerning the efficacy and outcome of percutaneous fluoroscopic synovial cyst rupture for treatment of facet joint synovial cysts. OBJECTIVE: The goal of this investigation was to assess the efficacy of fluoroscopically guided lumbar synovial cyst rupture, in particular for its relief of radicular symptoms and its potential to reduce the need for surgical intervention. STUDY DESIGN: Retrospective evaluation of a case series. SETTING: University hospital and urban public health care system. METHODS: With approval from the Institutional Review Board of Case Western Reserve University/ MetroHealth Medical Center, we reviewed the medical charts of patients with lumbar radiculopathy who underwent percutaneous lumbar synovial cyst rupture. The 30 patients in the cohort were treated by one pain specialist between 2006 and 2013. These patients were diagnosed with moderate to severe lower back pain, radiculopathy, and ranged in age from 42 to 80 years. Patients were followed up for a minimum of 6 months and up to 24 months. Pre- and post-procedure pain assessments were reviewed by clinical chart review. In addition post-procedure pain assessments and duration of pain relief were obtained with telephone interviews. Pain had been reported by the patients using a numeric rating scale of 0 - 10 (0 = no pain; 10 = worst possible pain). Charts were reviewed to determine if surgery was eventually performed to correct radicular symptoms. RESULTS: More than 6 months of pain relief was achieved in 14/30 patients (46%) and between one and 6 months of pain relief was achieved in 7/30 patients (23.3%). Nine patients (30.0%) had recurrence of the synovial cyst requiring repeat rupture and 6 patients (20.0%) required surgical intervention for cyst removal. A Wilcoxon signed-rank test demonstrated that the difference in numeric pain rating scale scores before and after the procedure was statistically significant (P < 0.0001). The average pain reduction was 71.2%. No complications were reported. LIMITATIONS: The results are limited by the retrospective nature of the data collection and the lack of detailed information regarding patients' functional improvement. CONCLUSIONS: Rupture of percutaneous lumbar synovial cysts in patients with lumbar radiculopathy was associated with immediate relief of radicular symptoms. In 80% of the patients, synovial cyst rupture eliminated the need for surgical interventions over the measured term. This minimally invasive procedure helps relieve pain in a subset of a patient population associated with these characteristics and is useful for management of this condition. Cyst expansion and failure to rupture with possible neuronal compression are the potential complications of this procedure. This complication did not occur in the study population. KEY WORDS: Fluoroscopically guided lumbar synovial cyst rupture, lumbar synovial cyst, lumbar zygapophyseal joint cyst, nonsurgical intervention, radiculopathy, spondylosis. PMID- 27676673 TI - Ultrasound-Guided Intermediate Site Greater Occipital Nerve Infiltration: A Technical Feasibility Study. AB - BACKGROUND: Two studies recently reported that computed tomography (CT) guided infiltration of the greater occipital nerve at its intermediate site allows a high efficacy rate with long-lasting pain relief following procedure in occipital neuralgia and in various craniofacial pain syndromes. OBJECTIVE: The purpose of our study was to evaluate the technical feasibility and safety of ultrasound guided intermediate site greater occipital nerve infiltration. STUDY DESIGN: Retrospective study. SETTING: This study was conducted at the imaging department of a 1,409 bed university hospital. METHODS: Local institutional review board approval was obtained and written consent was waived. In this retrospective study, 12 patients suffering from refractory occipital neuralgia or craniofacial pain syndromes were included between April and October 2014. They underwent a total of 21 ultrasound-guided infiltrations. Infiltration of the greater occipital nerve was performed at the intermediate site of the greater occipital nerve, at its first bend between obliqus capitis inferior and semispinalis capitis muscles with local anestetics and cortivazol. Technical success was defined as satisfactory diffusion of added iodinated contrast media in the fatty space between these muscles depicted on control CT scan. We also reported first data of immediate block test efficacy and initial clinical efficacy at 7 days, one month, and 3 months, defined by a decrease of at least 50% of visual analog scale (VAS) scores. RESULTS: Technical success rate was 95.24%. Patients suffered from right unilateral occipital neuralgia in 3 cases, left unilateral occipital neuralgia in 2 cases, bilateral occipital neuralgia in 2 cases, migraine in one case, cervicogenic headache in one case, tension-type headache in 2 cases, and cluster headache in one case. Block test efficacy was found in 93.3% (14/15) cases. Clinical efficacy was found in 80% of cases at 7 days, in 66.7% of cases at one month and in 60% of cases at 3 months. No major complications were noted. LIMITATIONS: Some of the limitations of our study include that it represents a single institution. The low number of infiltrations included in this study, for this guidance procedure, is another bias. CONCLUSIONS: This ultrasound-guided infiltration technique appears to be feasible, safe, non-ionizing, and fast when targeting the greater occipital nerve in its intermediate portion. This imaging guidance modality should be used in routine clinical practice. KEY WORDS: Greater occipital nerve, infiltration, ultrasound guidance, corticosteroids, occipital neuralgia, craniofacial pain syndrome. PMID- 27676674 TI - Contrast Runoff Correlates with the Clinical Outcome of Cervical Epidural Neuroplasty Using a Racz Catheter. AB - BACKGROUND: Epidural neuroplasty using a Racz catheter has a therapeutic effect. Studies have found no correlation between foraminal stenosis and the outcome of epidural neuroplasty, which is thought to depend on contrast runoff. OBJECTIVE: To examine the correlation between the contrast spread pattern and pain reduction in cervical epidural neuroplasty using a Racz catheter. STUDY DESIGN: Retrospective study. SETTING: An interventional pain-management practice in a university hospital. METHODS: Fluoroscopic images were reviewed retrospectively. The spread of contrast from the neural foramen to a nerve root was called contrast runoff. If the contrast did not spread in this manner, then there was no contrast runoff. We defined successful epidural neuroplasty as a 50% or greater reduction from the pre-procedure numeric rating scale (NRS) score for total pain, and an at least 40% reduction in the neck pain and disability scale (NPDS) score. RESULTS: This study reviewed 169 patients. Among the patients who had a contrast runoff pattern, the epidural neuroplasty was rated as successful in 96 (74.4%), 97 (75.2%), 86 (66.7%), and 79 (61.2%) cases one, 3, 6, and 12 months after the procedure, respectively. When there was no contrast runoff, the epidural neuroplasty was successful in 12 (30%), 12 (30%), 10 (25%), and 10 (25%) cases at one, 3, 6, and 12 months after the procedure (P < 0.001). Logistic regression of the contrast spread pattern and predicting successful epidural neuroplasty gave similar results. Patients with a contrast runoff pattern had odds ratios of 6.788, 7.073, 6.000, and 4.740 at one, 3, 6, and 12 months, respectively (P < 0.001). LIMITATIONS: This study lacked a control group, and the patients were not classified by their diagnosed disease, such as spinal stenosis, herniated nucleus pulposus, and post-spinal surgery syndrome. CONCLUSIONS: Cervical epidural neuroplasty with a contrast runoff pattern had a higher success rate. Contrast runoff should be observed during neuroplasty, even in the presence of foraminal stenosis. KEY WORDS: Cervical spinal pain, contrast, contrast runoff, epidural neuroplasty, percutaneous adhesiolysis, Racz catheter. PMID- 27676675 TI - The Effectiveness and Safety of Thermocoagulation Radiofrequency Treatment of the Ophthalmic Division (V1) and/or Maxillary (V2) and Mandibular (V3) Division in Idiopathic Trigeminal Neuralgia: An Observational Study. AB - BACKGROUND: Trigeminal neuralgia (TN) is a pain appearing in the ophthalmic (V1), maxillary (V2), and mandibular (V3) trigeminal branches. Pharmacologic treatment is the first line for TN; however, many patients prefer to receive minimally invasive treatment rather than medicine because of intolerable side effects. Thermocoagulation radiofrequency (TRF) is a minimally invasive treatment that has been shown to effectively treat the maxillary (V2) and mandibular (V3) divisions, but the safety of TRF treatment of the ophthalmic (V1) division has been controversial. OBJECTIVE: This study was to observe the effectiveness and safety of TRF treatment of the ophthalmic (V1) division of trigeminal branches in idiopathic TN patients. STUDY DESIGN: An observational study. SETTING: All of patients received temperature controlled TRF, the effectiveness and safety of TRF was assessed by VAS and complications. METHODS: Eighty patients with ophthalmic division (V1) or ophthalmic division (V1) combined with maxillary (V2) or mandibular (V3) divisions of idiopathic TN were treated with step-increased temperature TRF for 6 minutes. At a pulse width of 20 ms, the temperature was titrated up 2 degrees from 60 degrees to 66 degrees every 60 seconds, and then another 66 degrees or 68 degrees for 2 minutes. Meanwhile, the tip of the cannula was turned 180 degrees with each temperature titration. Patients were assessed for pain relief and corneal reflex, numbness, and masticatory muscle weakness at one week, one month, and 3 months after the procedure. RESULTS: Eighty patients were successfully treated with temperature controlled TRF for ophthalmic (V1) division. Excellent pain relief was achieved in 79 of 80 patients (98.75%) after one week, one month, and 3 months, and 78 of 80 patients (97.5%) patients experienced tolerable numbness. Only one patient lost the corneal reflex, 14 experienced a corneal reflex that was mildly decreased, and 2 patients felt a foreign body sensation in the ipsilateral eye after TRF, but there were no corneal ulcers, incidences of blindness, or other complications. LIMITATIONS: This study is limited by being an observation study and a non-prospective trial with a short-term follow-up period. CONCLUSION: Temperature controlled TRF to the ophthalmic division (V1) of the semilular ganglion is effectiveness and safe in TN. KEY WORDS: Thermocoagulation radiofrequency, pulsed radiofrequency, trigeminal neuralgia, ophthalmic division, trigeminal ganglion, pain, numbness, corneal reflex. PMID- 27676676 TI - Effectiveness and Impact of Capsaicin 8% Patch on Quality of Life in Patients with Lumbosacral Pain: An Open-label Study. AB - BACKGROUND: Capsaicin 8% patch (QutenzaTM) is mainly used to treat postherpetic neuralgia and HIV-associated neuropathy. Evidence of the efficacy of Qutenza in other forms of neuropathic pain is lacking. OBJECTIVE: To evaluate the analgesic effect and the impact on quality of life after a single application of the capsaicin 8% cutaneous patch in patients with lumbosacral pain. STUDY DESIGN: Prospective open-label study of capsaicin 8% patch in patients with lumbosacral pain. SETTING: Outpatient Pain and Palliative Care Center. METHODS: All recruited patients were evaluated prior to capsaicin 8% patch administration and were followed-up at 2 weeks, at 8 weeks, and at 12 weeks post administration. Visual analog scale (VAS) was used to record pain intensity and EQ-5D was used to assess the quality of life of the participants. RESULTS: Ninety patients met our inclusion criteria (54.4% men, mean age 59.1 +/- 9.2 years). At baseline the mean VAS score of the participants was 7.6 +/- 0.7. A statistically significant reduction of the VAS score between baseline and week 2 (mean VAS score 5.6 +/- 1.1, P < 0.001) was observed. The therapeutic effect further continued between week 2 and week 8 (mean VAS score 3.2 +/- 1.2, P < 0.001) and between week 8 and at endpoint at week 12 (mean VAS score 2.6 +/- 1.1, P < 0.001).Between baseline and weeks 2, 8, and 12 (end-point) a significant improvement in all 5 dimensions of EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) was observed (P < 0.001). LIMITATIONS: As it is an open-label study, a prospective randomized placebo-controlled study should be designed to confirm the effectiveness of capsaicin 8% patch in patients with lumbosacral pain. CONCLUSIONS: Administration of the capsaicin 8% patch resulted in a significant relief of neuropathic pain and a significant improvement of the quality of life of patients with lumbosacral neuropathic pain. KEY WORDS: Lumbosacral pain, peripheral pain, Qutenza, neuropathic pain, capsaicin, patch, quality of life, effectiveness. PMID- 27676677 TI - Timing of Platelet Rich Plasma Injections During Antithrombotic Therapy. AB - The use of platelet rich plasma (PRP) spans across many fields owing to its role in healing and as a natural alternative to surgery. PRP continues to grow however much of the literature is anecdotal or case report based and there is a lack of controlled trials to evaluate standards for PRP. The International Cellular Medical Society (ICMS) has developed guidelines to help with the safe advancement of PRP; however there remains a gap in literature concerning the timing of PRP injections in patients who are on antithrombotic therapy. The importance of an intact platelet surface membrane allows for the appropriate release of the healing bioproteins and growth factors granting PRP therapy its efficacy. This along with the proliferation of differentiated cells, enhancement of collagen synthesis, early angiogenesis and revascularization help promote the benefits of regeneration. The intrinsic and extrinsic pathways of the coagulation cascade are valuable in that disruption of this mechanism or prematurely activated platelets may result in limited efficacy. Anticoagulants and antiplatelet drugs are commonly used in patients who are candidates for PRP. As antithrombotic agents affect platelet stability, they will have an effect on PRP efficacy and must be discontinued at an appropriate time frame prior to injection therapy. Understanding the pharmacokinetics and platelet effects can help guide discussion on the proper timing of discontinuation and resumption of a particular antithrombotic agent. With future research, the establishment of clinical practice guidelines concerning PRP and antithrombotic therapy can help structure safe and efficacious means in which to promote healing and regeneration in a growing patient population. Platelet rich plasma, antithrombotic therapy, coagulation, platelet activation, regenerative medicine, growth factors. PMID- 27676678 TI - Evaluation of Bone Cancer Pain Induced by Different Doses of Walker 256 Mammary Gland Carcinoma Cells. AB - BACKGROUND: Cancer pain is a complex medical syndrome. Understanding its underlying mechanisms relies on the use of animal models which can mimic the human condition. A crucial component of this model is the quantity of tumor cells; however, the exact relationship between the doses of tumor cells on bone cancer pain is yet unknown. OBJECTIVE: We explored the relationship of different doses of Walker 256 carcinoma cells using a bone cancer pain model in rats, and evaluated its success and stability. STUDY DESIGN: Experimental animal study using a comparative design. SETTING: Experimental Animal Center and Tumor Institute of Traditional Chinese Medicine. METHODS: We constructed the bone cancer pain model by implanting Walker 256 carcinoma cells into the right tibia of Sprague-Dawley (SD) rats (150 - 170 g). Spontaneous pain, mechanical threshold, and paw withdrawal latency (PWL) were measured and x-ray, bone mineral density (BMD), histological, interleukin-1 beta (IL-1beta) mRNA, carboxyterminal telopeptide of type I collagen (ICTP), and bone alkaline phosphatase (BAP) were analyzed for bone pain model evaluation. RESULTS: The results showed that: (1) the 3 doses (3*105, 3.5*105, 4*105) of Walker 256 carcinoma cells can induce bone cancer pain from day 7 to day 21 after implantation into the right tibia of SD rats; (2) compared to the control group, 3*105, 3.5*105, and 4*105 Walker 256 carcinoma cells produced different pain manifestations, where the 3.5*105 dose of Walker 256 carcinoma cells resulted in the greatest bone cancer pain response; (3) the 3.5*105 dose induced the lowest mortality rate in rats; (4) Walker 256 carcinoma cells (3*105, 3.5*105, and 4*105) resulted in a significant decrease in the general condition and body weight of rats, where the 3.5*105 and 4*105 doses of carcinoma cells produced a greater effect than 3*105 dose of carcinoma cells; (5) progressive spontaneous pain, PWL, and mechanical threshold were exacerbated by 3.5*105 and 4*105 doses of carcinoma cells; (6) implantation of 3.5*105 and 4*105 doses of carcinoma cells induced progressive bone destruction and decrease in BMD; (7) ICTP and BAP were significantly increased following the implantation of 3.5*105 and 4*105 doses of carcinoma cells; (8) IL-1beta mRNA was significantly up-regulated in the spinal cord of rats implanted with 3.5*105 and 4*105 doses of carcinoma cells. LIMITATIONS: One limitation of this study was the small sample size; therefore, additional research is needed to provide better validation. Another limitation is the unavailability of small animal Micro computed tomography (CT), which is a more advanced and precise technique in determining bone marrow density than the x-ray imaging system we used. In addition, ethology experiments during late-stage tumor progression can be more objective. CONCLUSION: This study provides evidence that implantation of 3.5*105 and 4*105 dose of Walker 256 carcinoma cells produced the greatest effects in relation to the bone cancer pain model in SD rats, and 3.5*105 dose induced the lowest mortality rate. KEY WORDS: Bone cancer pain model, Walker 256 carcinoma cells, different doses. PMID- 27676679 TI - Currently Recommended TON Injectate Volumes Concomitantly Block the GON: Clinical Implications for Managing Cervicogenic Headache. AB - BACKGROUND: Headache (HA) is a significant cause of morbidity globally. Despite many available treatment options, HAs that are refractory to conservative management can be challenging to treat. Third occipital nerve (TON) and greater occipital nerve (GON) irritation are potential etiologic agents of primary and cervicogenic HAs that can be targeted using minimally invasive treatment options such as nerve blocks or radiofrequency ablation. However, a substantial number of patients that undergo radiofrequency ablation do not experience pain relief despite a positive diagnostic medial branch block (MBB). OBJECTIVE: In this study, we investigate the underlying cause for the high rate of false positives associated with MBBs by evaluating injectate spread in cadaveric subjects. STUDY DESIGN: Cadaveric study. SETTING: Academic medical center. METHODS: After obtaining exemption status from our Institutional Review Board, TON injections were performed on 5 preserved cadavers, a total of 10 TONs, using anatomic landmarks, partial dissection, and palpation to guide needle placement. Cadaveric dissections were performed to evaluate the location, vertical spread, and grossly observed injectate coating of the TON and GON for each quantity of methylene blue injectate, 0.3 mL and 0.5 mL, administered. RESULTS: The average distance between the TON and GON at their respective foraminal exit points was 1.81 cm. The average vertical spread for 0.3 mL and 0.5 mL of methylene blue injectate was 2.02 + 0.35 cm and 3.26 + 0.48 cm when performing a TON block. When using 0.3 mL injectate, both the TON and GON were simultaneously coated 60% of the time. After increasing the injectate volume to 0.5 mL, both the TON and GON were simultaneously coated 100% of the time. LIMITATIONS: The cadaveric design of this study presents limitations when translating cadaveric findings to the clinical setting. Also, the small sample size limits its power and generalizability. Lastly, the potential for researcher bias exists as the investigators were not blinded. CONCLUSIONS: This study demonstrates that currently recommended injectate volumes for TON blocks may result in concomitant coating of the GON. Conventional radiofrequency ablation (RFA) of these nerves may not lesion both the TON and GON given its restrictive circumferential lesioning diameter of 5 - 7 mm. As such, interventionalists should consider performing radiofrequency ablation to both the TON and GON after a positive TON block. KEY WORDS: Chronic pain, cervicogenic headache, third occipital nerve, greater occipital nerve, injectate spread, radiofrequency ablation. PMID- 27676680 TI - Intrathecal Bupivacaine Monotherapy with a Retrograde Catheter for the Management of Complex Regional Pain Syndrome of the Lower Extremity. AB - Complex regional pain syndrome (CRPS) presents a therapeutic challenge due to its many presentations and multifaceted pathophysiology. There is no approved treatment algorithm and clinical interventions are often applied empirically. In cases of CRPS where symptoms are localized to an extremity, a targeted treatment is indicated. We describe the use of intrathecal bupivacaine monotherapy, delivered through a retrograde catheter, in the treatment of CRPS affecting the lower extremity. The patient, a 57-year-old woman with a history of failed foot surgery, was seen in our office after 2 years of ineffective treatments with local blocks and neurolytic procedures. We advanced therapy to moderately invasive procedures with an emphasis on neuromodulation. A combined central and peripheral stimulation technique that initially provided 75% pain relief, failed to provide lasting analgesia. We proceeded with an intrathecal pump implant. Based on the results of dorsal root ganglion (DRG) mapping, L5-S1 was identified as the optimal target for therapy and a retrograde catheter was placed at this level. Various intrathecal medications were tested individually. An intrathecal morphine trial was ineffective (visual analog scale [VAS] 7), while intrathecal clonidine provided excellent pain relief (VAS 0) that was limited by severe side effects. Bupivacaine provided 100% analgesia with tolerable side effects (lower extremity weakness and minor bladder incontinence) and was selected for intrathecal infusion. After 14 months, bupivacaine treatment continued to control pain exacerbations. We conclude that CRPS patients benefit from early identification of the predominant underlying symptoms and a targeted treatment with moderately invasive techniques when less invasive techniques fail. KEY WORDS: Intrathecal bupivacaine, bupivacaine monotherapy, retrograde catheter, complex regional pain syndrome (CRPS), dual stimulation, dosal root ganglion (DRG) testing. PMID- 27676681 TI - Radiofrequency Ablation of the Sphenopalatine Ganglion Using Cone Beam Computed Tomography for Intractable Cluster Headache. AB - Percutaneous radiofrequency ablation (RFA) of the sphenopalatine ganglion (SPG) has been shown to be an effective modality of treatment for patients with intractable chronic cluster headaches (CHs). While the use of fluoroscopy for RFA of the SPG is common, to our knowledge there are no documented cases of procedures using cone beam computed tomography (CBCT) for image guidance. We present a case report of a patient suffering from chronic intractable CH with complete long-lasting relief after RFA of the SPG using CBCT. The case reaffirms the potential efficacy of RFA of the SPG in a case of chronic cluster headache as well as the use of CBCT as a superior alternative to bi-plane fluoroscopy for image guidance in the management of chronic CH. KEY WORDS: Cone beam computed tomography, sphenopalatine ganglion block, cluster headache, interventional pain, autonomic cephalalgia, radiofrequency ablation. PMID- 27676682 TI - Ultrasound in Anatomical Variation of Lateral Femoral Cutaneous Nerve. PMID- 27676683 TI - Fluoroscopically Guided Pulsed Radiofrequency Neurotomy Technique for the Treatment of Genitofemoral Neuralgia. PMID- 27676684 TI - Full Endoscopic Passing the Cavity of the Facet Approach for Treatment of Lumbar Disc Herniation. PMID- 27676685 TI - Long-term Postpartum Headache: PDPH Associated with Major Depression. PMID- 27676686 TI - Merit-Based Incentive Payment System (MIPS): Harsh Choices For Interventional Pain Management Physicians. AB - The Merit-based Incentive Payment System (MIPS) was created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to improve the health of all Americans by providing incentives and policies to improve patient health outcomes. MIPS combines 3 existing programs, Meaningful Use (MU), now called Advancing Care Information (ACI), contributing 25% of the composite score; Physician Quality Reporting System (PQRS), changed to Quality, contributing 50% of the composite score; and Value-based Payment (VBP) system to Resource Use or cost, contributing 10% of the composite score. Additionally, Clinical Practice Improvement Activities (CPIA), contributing 15% of the composite score, create multiple strategic goals to design incentives that drive movement toward delivery system reform principles with inclusion of Advanced Alternative Payment Models (APMs). Under the present proposal, the Centers for Medicare and Medicaid Services (CMS) has estimated approximately 30,000 to 90,000 providers from a total of over 761,000 providers will be exempt from MIPS. About 87% of solo practitioners and 70% of practitioners in groups of less than 10 will be subjected to negative payments or penalties ranging from 4% to 9%. In addition, MIPS also will affect a provider's reputation by making performance measures accessible to consumers and third-party physician rating Web sites.The MIPS composite performance scoring method, at least in theory, utilizes weights for each performance category, exceptional performance factors to earn bonuses, and incorporates the special circumstances of small practices.In conclusion, MIPS has the potential to affect practitioners negatively. Interventional Pain Medicine practitioners must understand the various MIPS measures and how they might participate in order to secure a brighter future. KEY WORDS: Medicare Access and CHIP Reauthorization Act of 2015, merit-based incentive payment system, quality performance measures, resource use, clinical practice improvement activities, advancing care information performance category. PMID- 27676687 TI - Proposed Medicare Physician Payment Schedule for 2017: Impact on Interventional Pain Management Practices. AB - The Centers for Medicare and Medicaid Services (CMS) released the proposed 2017 Medicare physician fee schedule on July 7, 2016, addressing Medicare payments for physicians providing services either in an office or facility setting, which also includes payments for office expenses and quality provisions for physicians. This proposed rule occurs in the context of numerous policy changes, most notably related to the Medicare Access & CHIP Reauthorization Act of 2015 (MACRA) and its Merit-Based Incentive Payment System (MIPS). The proposed rule affects interventional pain management specialists in reimbursement for evaluation and management services, as well as procedures performed in a facility or in-office setting.Changes in the proposed fee schedule impacting interventional pain management practices include adjustments to the meaningful use (MU) program, care management in patient-centered services, identification and review of potentially misvalued services, evaluation of moderate sedation services, Medicare telehealth services, updated geographic practice cost index, data collection on resources used in furnishing global services, reporting of modifier 25 for zero day global services, Medicare Advantage Part C provider and supplier enrollment, appropriate use criteria (AUC) for advanced imaging services, and Medicare shared savings programs. The proposed schedule has provided rates for new epidural codes with or without imaging (fluoroscopy or computed tomography [CT]) and a fee schedule for a new code covering endoscopic spinal decompression. Review of payment rates show major discrepancies in payment schedules with high payments for hospitals, 2,156% higher than in-office procedures. Some procedures which were converted from in office settings to ambulatory surgery centers (ASCs) are being reimbursed at 1,366% higher than ASCs. The Medicare Payment Advisory Commission (MedPAC) recommendation on avoiding the discrepancies and site-of-service differentials in in-office settings, hospital outpatient settings, and ASCs has not been agreed to by CMS. Thus, even though the changes appear to be minor in physician services and in-office service payment, these changes cumulatively have been reducing payments for interventional procedures. Further, in-office reimbursement is overall significantly lower than ASCs and hospital outpatient departments (HOPDs) specifically for intraarticular injections, peripheral nerve blocks, and peripheral neurolytic injections. The significant advantage also continues for hospitals in their reimbursement for facility fee for evaluation and management services.This health policy review describes various issues related to health care expenses, health care reform, and finally its effects on physician payments for all services and also for the services provided in an office setting. PMID- 27676688 TI - Facility Payments for Interventional Pain Management Procedures: Impact of Proposed Rules. AB - In the face of the progressive implementation of the Affordable Care Act (ACA), a significant regulatory regime, and the Merit-Based Incentive Payment System (MIPS), the Centers for Medicare and Medicaid Services (CMS) released its proposed 2017 hospital outpatient department (HOPD) and ambulatory surgery center (ASC) payment rules on July 14, 2016, and the physician payment schedule was released July 15, 2016. U.S. health care costs continue to increase, occupying 17.5% of the gross domestic product (GDP) in 2014 and surpassing $3 trillion in overall health care expenditure. Solo and independent practices face unique challenges and many are being acquired by hospitals or larger groups. This transfer of services to hospital settings is indisputably leading to an increase in the net cost to the system. Comparison of facility payments for interventional techniques in HOPD, ASC, and in-office settings shows wide variation for multiple interventional techniques. Major discrepancies in payment schedules are related to higher payments for hospitals than comparable treatments in in-office settings and ASCs. In-office procedures, which have been converted to ASC procedures, are reimbursed at as high as 1,366% higher than ASCs and 2,156% higher than in-office settings. The Medicare Payment Advisory Commission (MedPAC) has made recommendations on avoiding the discrepancies and site-of-service differentials in in-office settings, hospital outpatient settings, and ASCs. These have not been implemented by CMS. In addition, there have been slow reductions in reimbursements over the recent years, which continue to accumulate, leading to significant reductions in paymentsIn conclusion, equalization of site-of-service differentials will simultaneously improve reimbursement patterns for interventional pain management procedures, increase access and quality of care, and finally, reduce costs for CMS, extending Medicare solvency. KEY WORDS: Hospital outpatient departments, ambulatory surgery centers, physician in-office services, interventional pain management, interventional techniques. PMID- 27676689 TI - Structural Changes of Lumbar Muscles in Non-specific Low Back Pain: A Systematic Review. AB - BACKGROUND: Lumbar muscle dysfunction due to pain might be related to altered lumbar muscle structure. Macroscopically, muscle degeneration in low back pain (LBP) is characterized by a decrease in cross-sectional area and an increase in fat infiltration in the lumbar paraspinal muscles. In addition microscopic changes, such as changes in fiber distribution, might occur. Inconsistencies in results from different studies make it difficult to draw firm conclusions on which structural changes are present in the different types of non-specific LBP. Insights regarding structural muscle alterations in LBP are, however, important for prevention and treatment of non-specific LBP. OBJECTIVE: The goal of this article is to review which macro- and/or microscopic structural alterations of the lumbar muscles occur in case of non-specific chronic low back pain (CLBP), recurrent low back pain (RLBP), and acute low back pain (ALBP). STUDY DESIGN: Systematic review. SETTING: All selected studies were case-control studies. METHODS: A systematic literature search was conducted in the databases PubMed and Web of Science. Only full texts of original studies regarding structural alterations (atrophy, fat infiltration, and fiber type distribution) in lumbar muscles of patients with non-specific LBP compared to healthy controls were included. All included articles were scored on methodological quality. RESULTS: Fifteen studies were found eligible after screening title, abstract, and full text for inclusion and exclusion criteria. In CLBP, moderate evidence of atrophy was found in the multifidus; whereas, results in the paraspinal and the erector spinae muscle remain inconclusive. Also moderate evidence occurred in RLBP and ALBP, where no atrophy was shown in any lumbar muscle. Conflicting results were seen in undefined LBP groups. Results concerning fat infiltration were inconsistent in CLBP. On the other hand, there is moderate evidence in RLBP that fat infiltration does not occur, although a larger muscle fat index was found in the erector spinae, multifidus, and paraspinal muscles, reflecting an increased relative amount of intramuscular lipids in RLBP. However, no studies were found investigating fat infiltration in ALBP. Restricted evidence indicates no abnormalities in fiber type in the paraspinal muscles in CLBP. No studies have examined fiber type in ALBP and RLBP. LIMITATIONS: Lack of clarity concerning patient definitions, exact LBP symptoms, and applied methods. CONCLUSIONS: The results indicate atrophy in CLBP in the multifidus and paraspinal muscles but not in the erector spinae. No atrophy was shown in RLBP and ALBP. Fat infiltration did not occur in RLBP, but results in CLBP were inconsistent. No abnormalities in fiber type in the paraspinal muscles were found in CLBP. KEY WORDS: Low back pain, non-specific, chronic, recurrent, acute, muscle structure, fat infiltration, cross-sectional area, fiber type, review. PMID- 27676690 TI - Fabrication of Hollow Materials by Fast Pyrolysis of Cellulose Composite Fibers with Heterogeneous Structures. AB - A facile method for the fabrication of inorganic hollow materials from cuprammonium cellulose composite filaments based on fast pyrolysis has been developed. Unlike Ostwald ripening, approaches based on the Kirkendall effect, and other template methods, this process yielded hollow materials within 100 s. The heterogeneous structure of the cellulose composite fibers and the gradient distribution of the metal oxides are the main reasons for the formation of the hollow structure. The diameter, wall thickness, and length of the hollow microfibers could be conveniently controlled. With their perfect morphology, these hollow structural materials have great potential for use in various fields. PMID- 27676691 TI - A case of intravascular papillary endothelial hyperplasia of the stomach leading to a novel hypothesis for the pathogenesis. PMID- 27676693 TI - Cancer stem cells: A product of clonal evolution? AB - The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells. Similarly, pro-survival or proliferation signalling often exhibited by stem cells is regularly reported as being upregulated by CSC. Here we review evidence suggesting that many aspects of CSCs are more readily described by clonal evolution. As an example, cancer cells often exhibit copy number gains of genes involved in drug-efflux proteins and pro survival signalling. Consequently, clonal selection for stem cell traits may result in cancer cells developing "stemness" traits which impart a fitness advantage, without strictly following a CSC model. Finally, since symmetric cell division would give rise to more cells than asymmetric division, it is expected that more advanced tumours would depart from a CSC. Collectively, these observations suggest clonal evolution may explain many aspects of the CSC. PMID- 27676692 TI - Diurnal and Nocturnal Flight Activity of Blow Flies (Diptera: Calliphoridae) in a Rainforest Fragment in Brazil: Implications for the Colonization of Homicide Victims. AB - Nocturnal flight of blow flies (Diptera: Calliphoridae) is a controversial issue in forensic entomology. We performed two field experiments to investigate the diurnal and nocturnal activity of six blow fly species in a rainforest fragment in Brazil. Initially, nocturnal (17:30-05:30) versus diurnal (05:30-17:30) flight activity was investigated. Only 3.9% of adults were collected at night, mostly the native species Mesembrinella bicolor, and nocturnal oviposition did not occur. In the second experiment, collection of adults took place at the following intervals: 05:30-08:30, 08:30-11:30, 11:30-14:30, and 14:30-17:30. The proportions of adults did not differ significantly among the four diurnal intervals, except for Hemilucilia segmentaria, which was captured more frequently in the early morning. Calliphoridae has predominantly diurnal behavior, not laying eggs in darkness. The association of the native species M. bicolor, Hemilucilia semidiaphana, and H. segmentaria to forested areas reinforces the forensic relevance of data on their flight pattern. PMID- 27676694 TI - Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales. AB - In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long-acting PH20-Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (~1.5 * 1.0 * 0.7 nm) chemotherapy, trastuzumab (10-15 nm) biotherapy, and gold nanorod (~100 * 35 nm) thermotherapy. In traditional 2D cultures, PH20 and PH20-Fc have little influence on cytotoxicity due to lack of a tumor microenvironment. However, the cytotoxicities of the three therapeutic agents in 3D tumor spheroids are all enhanced by PH20 or PH20-Fc because hyaluronan degradation facilitates therapeutic penetration and accumulation. Furthermore, in vivo evaluations reveal that the significantly prolonged circulation time of PH20-Fc leads to accumulation in the tumor and subsequent hyaluronan degradation. Consequently, PH20-Fc coadministration further inhibits tumor growth. The performance of PH20 Fc varies for the three therapeutic agents due to their different nanoscales. Trastuzumab benefits most from combination with PH20-Fc. The results provide here novel insights that can aid in the development of more effective hyaluronidase based therapeutic systems. PMID- 27676695 TI - Dose and Duration of Opioid Use in Patients with Cancer and Noncancer Pain at an Outpatient Hospital Setting in Malaysia. AB - BACKGROUND: There are currently limited data available on the patterns of opioid prescribing in Malaysia. This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain. METHODS: This retrospective, cross-sectional study was conducted at an outpatient hospital setting in Malaysia. All prescriptions for opioids (dihydrocodeine, fentanyl, morphine, and oxycodone) issued between January 2013 and December 2014 were examined. The number of prescriptions and patients, the distribution of mean daily dose, annual total days covered with opioids, and annual total opioid dose at the individual level were calculated and stratified by noncancer and cancer groups. RESULTS: A total of 1015 opioid prescriptions were prescribed for 347 patients from 2013 to 2014. Approximately 41.5% of patients (N = 144/347) and 58.5% (N = 203/347) were associated with noncancer and cancer diagnosis, respectively. Oxycodone (38.0%) was the highest prescribed primarily for the noncancer group. The majority of patients in both noncancer (74.3%) and cancer (60.4%) groups were receiving mean daily doses of < 50 mg morphine equivalents. The chronic use of opioids (> 90 days per year) was associated with 21.8% of patients in the noncancer group and 17.5% in the cancer group. CONCLUSIONS: The finding from this study showed that 41.5% of opioid users at an outpatient hospital setting in Malaysia received opioids for noncancer pain and 21.8% of these users were using opioids for longer than 90 days. The average daily dose in the majority of patients in both groups of noncancer and cancer was modest. PMID- 27676696 TI - Nerve growth factor release from the urothelium increases via activation of bladder C-fiber in rats with cerebral infarction. AB - AIMS: There are some reports that bladder C-fibers are partially involved in detrusor overactivity in patients with brain lesions. We investigated the contribution of bladder C-fiber to decreased bladder capacity in rats with cerebral infarction. METHODS: Cerebral infarction was induced under halothane anesthesia by left middle cerebral artery occlusion with 4-0 nylon thread in female Sprague-Dawley rats. Intramural amounts of ATP and prostaglandin E2 , in vivo and in vitro ATP, NGF, and prostaglandin E2 release from the distended bladder urothelium, and changes in mRNA expressions of sensor molecules and receptors were monitored 6 h after the occlusion. Cystometry was performed in rats with or without resiniferatoxin pretreatment. RESULTS: Overexpression of sensor molecule, transient receptor potential vanilloid-type channel 1, acid sensing ion channel 2, purinergic receptors P2X3 , and M2 /M3 muscarinic receptors was found in the bladder. These changes were accompanied by increases in ATP and NGF release from the urothelium. In contrast, when bladder C-fibers were desensitized by resiniferatoxin, no increase in NGF release from the urothelium was found either in vivo or in vitro. There was no difference in the percentage decrease in bladder capacity between cerebral infarction rats pretreated with resiniferatoxin and cerebral infarction rats without pretreatment. CONCLUSIONS: Results indicate that expression of sensor molecules in the bladder is altered by distant infarction in the brain. ATP and NGF release from the urothelium also increased. NGF release was related to activation of bladder C-fibers. Bladder C-fibers might not contribute much to decreased bladder capacity caused by cerebral infarction. PMID- 27676698 TI - Aggression in Autism Spectrum Disorder: Supporting the Entire Family. AB - CASE: Juanita is a 13-year-old non-verbal Latina girl with autism spectrum disorder, moderate intellectual disability, and a seizure disorder whose aggressive behaviors toward her parents have significantly worsened over the past few months.Juanita's monolingual Spanish-speaking parents are here today for medication management at her primary care clinic. The parents report that Juanita pinches them, pulls their hair, and hits her head with her fists. Her aggression toward them is usually triggered by feelings of frustrations, leaving her parents feeling like they have to walk on eggshells around her and have led to differing parenting styles. Her father reports that he tries to avoid getting her upset and prefers to watch TV with her, whereas her mother takes on the day-to-day caretaking. Although he wants to take a more active role in parenting Juanita, when he tries, Juanita becomes more aggressive and reacts violently toward him.During the visit, Juanita keeps her eyes downcast, is withdrawn, and some strain is noted between her parents. While speaking to them, Juanita's mother chimes in and reports that she considers herself the primary caregiver and the one who knows her daughter the best. She often dismisses Juanita's father's reporting, saying that "he doesn't know what really is going on." When Juanita is taken to the restroom by her mother, her father tearfully reports that he feels that it may be best for everyone that he leaves the family because of Juanita's worsening aggression toward him and the toll it is taking on his marriage. How would you approach her management? PMID- 27676699 TI - How Does Aging Affect Presentation and Management of Biliary Stones? AB - Common bile duct (CBD) stones are common in elderly adults, but the effect of aging on the presentation of CBD stones remains to be evaluated. Recent studies have demonstrated that the clinical presentation of CBD stones may vary with age. Younger adults may present with classical biliary colic symptoms, whereas elderly adults may have no unapparent clinical features. Younger adults with CBD stones were significantly more likely to have abnormal liver function tests than those without. The sensitivity and accuracy of transabdominal ultrasound scans in screening for CBD stones increases with age. Antibiotic agents should be promptly administered to individuals with CBD stones complicated by cholangitis, but the effects of pharmacotherapy on renal function should be considered in elderly adults. Endoscopic retrograde cholangiopancreatography (ERCP) is considered to be first-line treatment for CBD stones, and endoscopic biliary sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD) along with ERCP is an adequate biliary drainage method in individuals with CBD stones. EPBD has a lower bleeding risk but higher post-ERCP risk of pancreatitis than EST. Longer-duration (>1 minute) EPBD may be preferred over EST because it is associated with a comparable risk of pancreatitis but a lower rate of overall complications, although recurrent cholangitis or unfavorable outcomes will increase during CBD dilation or in the presence of residual CBD stones. PMID- 27676700 TI - Five New Triterpenoid Saponins from the Rhizomes of Panacis majoris and Their Antiplatelet Aggregation Activity. AB - Five new triterpenoid saponins (1-5) and four known triterpenoid saponins, ginsenoside Re5 (6), majonoside R1 (7), 24(R)-majonoside R1 (8), and ginsenoside Rf (9), were isolated from the rhizomes of Panacis majoris. The structures of new compounds were elucidated as (20S,24S,25R*)-6-O-[beta-D-glucopyranosyl-(1 -> 2) beta-D-glucopyranosyl]-dammar-20,24-epoxy-3beta,6alpha,12beta,25,26-pentaol (1), (20S,24R,25R)-6-O-[beta-D-glucopyranosyl-(1 -> 2)-beta-D-glucopyranosyl]-dammar 20,24-epoxy-3beta,6alpha,12beta,25,26-pentaol (2), (20S)-6-O-[beta-D glucopyranosyl-(1 -> 2)-beta-D-glucopyranosyl]-dammar-20,25-epoxy 3beta,6alpha,12beta,24alpha-tetraol (3), 6-O-[beta-D-glucopyranosyl-(1 -> 2)-beta D-glucopyranosyl]-dammar-3beta,6alpha,12beta,20S,24R,25-hexaol (4), and 6-O-[beta D-glucop-yranosyl-(1 -> 2)-beta-D-glucopyranosyl]-dammar-25(26)-ene 3beta,6alpha,12beta,20S,24R-pentaol (5) on the basis of extensive spectral analysis and chemical methods. Ginsenoside Re5 was isolated from the plant for the first time. The similarities of the nine compounds lie in the fact that their aglycones are conjoined with the same glucopyranose moieties, the same linkage of the glycosyl chains, and the same glycosylation sites, while they have a varied C 17 side chain. Compounds 3 and 5 exhibited moderate antiplatelet aggregation activities induced by adenosine diphosphate with IC50 values of 23.24 and 18.43 uM, respectively. Compound 5 displayed moderate inhibition of arachidonic acid induced platelet aggregation with an IC50 value of 30.11 uM. PMID- 27676697 TI - Phenotyping, Etiological Factors, and Biomarkers: Toward Precision Medicine in Autism Spectrum Disorders. AB - Despite the progress made in understanding the biology of autism spectrum disorder (ASD), effective biological interventions for the core symptoms remain elusive. Because of the etiological heterogeneity of ASD, identification of a "one-size-fits-all" treatment approach will likely continue to be challenging. A meeting was convened at the University of Missouri and the Thompson Center to discuss strategies for stratifying patients with ASD for the purpose of moving toward precision medicine. The "white paper" presented here articulates the challenges involved and provides suggestions for future solutions. PMID- 27676701 TI - Trypsin and MALDI matrix pre-coated targets simplify sample preparation for mapping proteomic distributions within biological tissues by imaging mass spectrometry. AB - Prefabricated surfaces containing alpha-cyano-4-hydroxycinnamic acid and trypsin have been developed to facilitate enzymatic digestion of endogenous tissue proteins prior to matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Tissue sections are placed onto slides that were previously coated with alpha-cyano-4-hydroxycinnamic acid and trypsin. After incubation to promote enzymatic digestion, the tissue is analyzed by MALDI IMS to determine the spatial distribution of the tryptic fragments. The peptides detected in the MALDI IMS dataset were identified by Liquid chromatography-tandem mass spectrometry/mass spectrometry. Protein identification was further confirmed by correlating the localization of unique tryptic fragments originating from common parent proteins. Using this procedure, proteins with molecular weights as large as 300 kDa were identified and their distributions were imaged in sections of rat brain. In particular, large proteins such as myristoylated alanine-rich C kinase substrate (29.8 kDa) and spectrin alpha chain, non-erythrocytic 1 (284 kDa) were detected that are not observed without trypsin. The pre-coated targets simplify workflow and increase sample throughput by decreasing the sample preparation time. Further, the approach allows imaging at higher spatial resolution compared with robotic spotters that apply one drop at a time. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27677048 TI - Time of day affects implicit memory for unattended stimuli. AB - We investigated whether circadian arousal affects perceptual priming as a function of whether stimuli were attended or ignored during learning. We tested 160 participants on- and off-peak with regards to their circadian arousal. In the study phase, they were presented with two superimposed pictures in different colours. They had to name the pictures of one colour while ignoring the others. In the test phase, they were presented with the same and randomly intermixed new pictures. Each picture was presented in black colour in a fragment completion task. Priming was measured as the difference in fragmentation level at which the pictures from the study phase were named compared to the new pictures. Priming was stronger for attended than ignored pictures. Time of day affected priming only for ignored pictures, with stronger priming effects off-peak than on-peak. Thus, circadian arousal seems to favour the encoding of unattended materials specifically at off-peak. PMID- 27676702 TI - Cascading effects of BPT for child internalizing problems and caregiver depression. AB - Behavioral Parent Training (BPT) is the standard of care for early onset (3 to 8years old) disruptive behavior disorders (DBDs). Preliminary evidence suggests that BPT may also produce cascading treatment effects for comorbid and interrelated symptomatology in children, primarily internalizing problems, as well as symptomatology in multiple systems of the family, including caregiver depressive symptomatology. What is less well understood, however, is why and how BPT functions to impact these multiple symptom clusters within and between family members. Accordingly, this manuscript aims to serve as a conceptual and theoretical consideration of the mechanisms through which BPT may produce generalized treatment effects among children with early onset DBDs and internalizing problems, as well as the psychosocial difficulties among their caregivers. It is our intention that the hypothesized mechanisms highlighted in this review may guide advances in clinical research, as well as assessment and practice. PMID- 27677049 TI - Traumatic stress, neural self and the spiritual mind. AB - According to recent findings stressful experiences may influence various physiological disturbances and also neuroanatomical changes and some studies also show that psychotherapy and meditation may influence brain functions. Traumatic stress is frequently related to a dissociative response that disintegrates conscious experience. In this context, self-reflection is an essential principle in the process of posttraumatic growth related to spiritual experiences and meditation states that enable mental integration and create the novel integrated self. According to recent findings there is no widely accepted evidence about specific neural mechanisms of processes related to mental integration linked to the spiritual experiences and meditation. Nevertheless there is growing evidence that these integrative experiences are related to various alterations in the brain's physiology and morphology. These findings provide a new paradigm for understanding of mental disorders and emphasize the fundamental role of mental integration and integrated self in the therapy of psychiatric disorders. PMID- 27677050 TI - Audience gaze while appreciating a multipart musical performance. AB - Visual information has been observed to be crucial for audience members during musical performances. The present study used an eye tracker to investigate audience members' gazes while appreciating an audiovisual musical ensemble performance, based on evidence of the dominance of musical part in auditory attention when listening to multipart music that contains different melody lines and the joint-attention theory of gaze. We presented singing performances, by a female duo. The main findings were as follows: (1) the melody part (soprano) attracted more visual attention than the accompaniment part (alto) throughout the piece, (2) joint attention emerged when the singers shifted their gazes toward their co-performer, suggesting that inter-performer gazing interactions that play a spotlight role mediated performer-audience visual interaction, and (3) musical part (melody or accompaniment) strongly influenced the total duration of gazes among audiences, while the spotlight effect of gaze was limited to just after the singers' gaze shifts. PMID- 27677051 TI - Daydreams and trait affect: The role of the listener's state of mind in the emotional response to music. AB - Music creates room for the mind to wander, mental time travel, and departures into more fantastical worlds. We examined the mediating role of daydreams and the moderating function of personality differences for the emotional response to music by using a moderated mediation approach. The results showed that the valence of daydreams played a mediating role in the reaction to the musical experience: happy music was related to more positive daydreams, which were associated with greater relaxation with the happy music and to greater liking of the happy music. Furthermore, negative affect (trait) moderated the direct effect of sad vs. happy music on the liking of the music: individuals with high scores on negative affect preferred sad music. The results are discussed with regard to the interplay of general and personality-specific processes as it is relevant to better understand the effects music can have on the listeners. PMID- 27677052 TI - Using hypnosis to model Fregoli delusion and the impact of challenges on belief revision. AB - Fregoli delusion involves the belief that strangers are known people in disguise. We aimed to model aspects of this delusion for the first time using hypnosis. We informed hypnotised subjects that someone would enter the room (a confederate) and they would believe this person was someone they knew in disguise. After testing their reaction to the confederate, we challenged their delusion by directly contradicting their belief and then asking them to focus on the confederate's voice and gait. Finally, we indexed whether they could identify photographs of the confederate. We found that just over half of our high hypnotisable subjects identified the confederate as someone they knew in disguise. Although many highs abandoned their belief in response to challenges, some maintained strong, unwavering conviction that the confederate was a known person. We discuss these findings in terms of how evidence might be evaluated during both hypnotic and clinical delusions. PMID- 27677053 TI - Free love? On the relation between belief in free will, determinism, and passionate love. AB - Is love possible if we are not free? Some philosophers consider that true love is necessarily free, while others think that the nature of love makes it incompatible with a certain type of freedom. Here, we explored the relationship between feelings of passionate love, belief in free will and determinism across three online studies. In Study 1 (N=257), participants who believed strongly in free will (or determinism) expressed stronger passionate love. In Study 2 (N=305), we again found a positive association between belief in free will (or determinism) and passionate love, although the passionate love-determinism relationship seems more conditional. Finally, Study 3 (N=309) confirmed the relationship between belief in free will and passionate love but not between belief in determinism and passionate love. These findings, along with a meta analysis, suggest that both beliefs in free will and determinism are compatible with passionate love. PMID- 27677055 TI - Building a 'Repository of Science': The importance of integrating biobanks within molecular pathology programmes. AB - Repositories containing high quality human biospecimens linked with robust and relevant clinical and pathological information are required for the discovery and validation of biomarkers for disease diagnosis, progression and response to treatment. Current molecular based discovery projects using either low or high throughput technologies rely heavily on ready access to such sample collections. It is imperative that modern biobanks align with molecular diagnostic pathology practices not only to provide the type of samples needed for discovery projects but also to ensure requirements for ongoing sample collections and the future needs of researchers are adequately addressed. Biobanks within comprehensive molecular pathology programmes are perfectly positioned to offer more than just tumour derived biospecimens; for example, they have the ability to facilitate researchers gaining access to sample metadata such as digitised scans of tissue samples annotated prior to macrodissection for molecular diagnostics or pseudoanonymised clinical outcome data or research results retrieved from other users utilising the same or overlapping cohorts of samples. Furthermore, biobanks can work with molecular diagnostic laboratories to develop standardised methodologies for the acquisition and storage of samples required for new approaches to research such as 'liquid biopsies' which will ultimately feed into the test validations required in large prospective clinical studies in order to implement liquid biopsy approaches for routine clinical practice. We draw on our experience in Northern Ireland to discuss how this harmonised approach of biobanks working synergistically with molecular pathology programmes is a key for the future success of precision medicine. PMID- 27677054 TI - Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America. AB - AIM: To assess trends in survival and geographic disparities among children (0-14 years) with chronic myeloid leukaemia (CML) before and after the introduction of molecular therapy, namely tyrosine kinase inhibitors (TKIs) in Southern-Eastern European (SEE) countries and the USA. METHODS: We calculated survival among children with CML, acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) in 14 SEE (1990-2014) cancer registries and the U.S. Surveillance, Epidemiology and End Results Program (SEER, 1990-2012). We used Kaplan-Meier curves and multivariate Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 369 CML cases, substantial improvements were noted in 2-year survival during the post-TKI (range: 81-89%) compared to pre-TKI period (49-66%; HR: 0.37, 95% CI: 0.23-0.60). Risk of death was three times higher for <5-year-old children versus those aged 10-14 years (HR: 3.03, 95% CI: 1.85-4.94) and 56% higher for those living in SEE versus SEER (HR: 1.56, 95% CI: 1.01-2.42). Regardless of geographic area and period of TKI administration, however, age seems to be a significant determinant of CML prognosis (pre-TKI period, HR0-4y: 2.71, 95% CI: 1.53-4.79; post-TKI period, HR0 4y: 3.38, 95% CI: 1.29-8.85). Noticeably, post-TKI survival in CML overall approximates that for ALL, whereas therapeutic advancements for AML remain modest. CONCLUSION: Registry data show that introduction of molecular therapies coincides with revolutionised therapeutic outcomes in childhood CML entailing dramatically improved survival which is now similar to that in ALL. Given that age disparities in survival remain substantial, offering optimal therapy to entire populations is an urgent priority. PMID- 27677056 TI - Assessment of the extent of microcalcifications to predict the size of a ductal carcinoma in situ: comparison between tomosynthesis and conventional mammography. AB - OBJECTIVES: The objective was to determine if digital tomosynthesis of the breast (DBT) assesses the extension of ductal carcinoma in situ (DCIS) with higher precision than mammography (MG). MATERIAL AND METHODS: The local ethics committee approved this retrospective study including 26 patients with DCIS, which were rated by three radiologists. Statistics were performed using intraclass correlation (ICC) for interreader agreement and the Pearson correlation for correlation of MG and DBT. Standard of reference was the histologic extension. RESULTS: The ICC was excellent. Correlation between MG and histology was 0.879 (P<.01) and for DBT and histology was 0.914 (P<.01). CONCLUSION: DBT provides a slightly better estimation of the size of a DCIS than MG. PMID- 27677057 TI - Camelid VH H affinity ligands enable separation of closely related biopharmaceuticals. AB - Interest in new and diverse classes of molecules such as recombinant toxins, enzymes, and blood factors continues to grow for use a biotherapeutics. Compared to monoclonal antibodies, these novel drugs typically lack a commercially available affinity chromatography option, which leads to greater process complexity, longer development timelines, and poor platformability. To date, for both monoclonal antibodies and novel molecules, affinity chromatography has been mostly reserved for separation of process-related impurities such as host cell proteins and DNA. Reports of affinity purification of closely related product variants and modified forms are much rarer. In this work we describe custom affinity chromatography development using camelid VH H antibody fragments as "tunable" immunoaffinity ligands for separation of product-related impurities. One example demonstrates high selectivity for a recombinant immunotoxin where no binding was observed for an undesired deamidated species. Also discussed is affinity purification of a coagulation factor through specific recognition of the gamma-carboxylglutamic acid domain. PMID- 27677059 TI - Nurturing Our Young. PMID- 27677058 TI - Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level. AB - Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2-4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child's life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. PMID- 27677061 TI - Perceptions of Home Health Nurses Regarding Suffering, Artificial Nutrition, and Hydration in Late-Stage Dementia. AB - The purpose of this study was to explore perceptions of home healthcare nurses related to suffering, artificial nutrition and hydration in people with late stage dementia, and if these perceptions influence care to people with dementia and their families. Part of a mixed-methods study, the qualitative portion examined perceptions of home healthcare nurses in a rural area in the southern United States. Seventeen home healthcare nurses participated in this study. Semistructured focus group interview questions were used. Constant comparative analysis was the method used for coding transcripts. Three themes emerged from the analysis: patient/family comfort, futility, and symbols of suffering. Although many of the nurses reported that artificial nutrition and hydration was of comfort to the patient and family because of the potential for "starving," they also felt it prolonged the patient's suffering due to the invasive procedure, need for restraints, and possibility of fluid overload. Several nurses felt that artificial nutrition and hydration gave a sense of false hope to the family that the patient would live longer. The perceptions of these home healthcare nurses influence their care to people with dementia and their families related to artificial nutrition and hydration, possibly based on experience. Their perceptions could influence family decisions regarding treatment options. Further research and education with home healthcare nurses is vital to ensure nurses are appropriately caring for patients with dementia and their families. PMID- 27677062 TI - What Influences Home Care Nurses to Accept or Reject Precepting Opportunities? A Pilot Study. AB - Nurse managers and nursing faculty report, anecdotally, on their difficulty identifying nurses willing to precept new staff or students. To understand more about this topic, we queried home care nurses at a small agency on their perceived incentives and barriers to precepting, their preceptor status, generation of birth, and birth order. The purpose of this pilot study was to identify home care nurses' perceived incentives and barriers to becoming a preceptor. We also sought to examine possible relationships between preceptor status, generation of birth, and ordinal position of birth. PMID- 27677063 TI - Exposing Baccalaureate Nursing Students to Transitional Care. AB - Management and facilitation of care transitions from hospital to alternative settings requires skill and attention to avoid adverse events. Several interprofessional organizations and nurse leaders have called for the expansion and redesign of undergraduate nursing curricula to include care transitions. Yet there is little evidence describing how undergraduate baccalaureate nursing students are educated on this critical topic or how successful they are in improving student knowledge about care transitions. To address this gap, an in classroom and clinical experience was implemented to prepare students to manage and facilitate care transitions from the hospital to alternative settings including the home. Perceptions of undergraduate nursing students and home healthcare nurse preceptors were assessed via an electronic survey that was emailed to participants. Forty-eight responses to the survey were received. Students agreed this experience contributed to their understanding of caring for adults and older adults who are experiencing a care transition and they had a good understanding of care transitions to apply to their future nursing courses. Home healthcare nurse preceptors agreed they were able to demonstrate transitional care and that students were engaged. Future work should include expanding transitional care immersion to other care settings as well as the inclusion of additional healthcare disciplines in care transition education. PMID- 27677064 TI - Educating Home Healthcare Nurses About Heart Failure Self-Care. AB - The ability of home healthcare nurses to effectively educate patients with heart failure (HF) on appropriate self-care is key to lowering the hospital readmission rates and other adverse outcomes. Evidence indicates, however, that nurses often lack current knowledge about HF self-care. Furthermore, patient education often fails to produce health literacy. Thus, this educational intervention for home healthcare nurses included content about key aspects of managing HF (e.g., diet, medications), as well as how to use the teach-back method during patient education. Pre- and posttesting (using the Nurses' Knowledge of HF Education Principles Questionnaire) and role-playing were used to evaluate the intervention delivered to 33 home care nurses. Findings exposed knowledge deficits regarding high-sodium foods, symptoms indicating deterioration, problematic weight gain, fluid management, as well as other topics related to HF. The education was partially effective in addressing these nurses' knowledge gaps. The evidence based education for home healthcare nurses suggests that not only may nurses lack knowledge essential to teaching HF self-care; they may also lack effective patient education skills such as using the teach-back method. PMID- 27677066 TI - Choosing Wisely. PMID- 27677065 TI - Home Health Nurse Collaboration in the Medical Neighborhood of Children with Medical Complexity. AB - The objectives of this study were to describe how home healthcare nurses collaborate with other clinicians caring for children with medical complexity, and identify barriers to collaboration within the medical neighborhood. Using qualitative data obtained from 20 semistructured interviews (15 English, 5 Spanish) with primary caregivers of children with medical complexity and 18 home healthcare nurses, researchers inquired about experiences with home healthcare nursing services for these children. During an iterative analysis process, recurrent themes were identified by their prevalence and salience in the data. Home healthcare nurses collaborate with many providers within the medical neighborhood of children with medical complexity and perform many different collaborative tasks. This collaboration is valued by caregivers and nurses, but is inconsistent. Home healthcare nurses' communication with other clinicians is important to the delivery of good-quality care to children with medical complexity at home, but is not always present. Home healthcare nurses reported inability to share clinical information with other clinicians, not receiving child-specific information, and lack of support for clinical problem-solving as concerns. Barriers for optimal collaboration included lack of preparedness of parents, availability of physicians for clinical support, reimbursement for collaborative tasks, variability in home healthcare nurses' tasks, and problems at nursing agency level. Home healthcare nurses' collaboration with other clinicians is important, but problems exist in the current system of care. Optimizing collaboration between home healthcare nurses and other clinicians will likely have a positive impact on these children and their families. PMID- 27677067 TI - Farxiga and Fetzima Mix-Ups. PMID- 27677068 TI - Protecting the Staff When Using Disinfectants in the Home. PMID- 27677069 TI - A Day in the Life of a Rural Home Healthcare Nurse. PMID- 27677070 TI - Snowbirds. PMID- 27677071 TI - Legislature Update on the Family Caregiver Support and Designated CareGiver Acts. PMID- 27677072 TI - Embracing Palliative Care Through Innovation. PMID- 27677073 TI - Spirituality and Health Education in a Faith Community. PMID- 27677074 TI - Perceptions of Home Health Nurses Regarding Suffering, Artificial Nutrition, and Hydration in Late-Stage Dementia. PMID- 27677075 TI - Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis. AB - Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality. Observed during CRC tumorigenesis is loss of post transcriptional regulation of tumor-promoting genes such as COX-2, TNFalpha and VEGF. Overexpression of the RNA-binding protein HuR (ELAVL1) occurs during colon tumorigenesis and is abnormally present within the cytoplasm, where it post transcriptionally regulates genes through its interaction with 3'UTR AU-rich elements (AREs). Here, we examine the therapeutic potential of targeting HuR using MS-444, a small molecule HuR inhibitor. Treatment of CRC cells with MS-444 resulted in growth inhibition and increased apoptotic gene expression, while similar treatment doses in non-transformed intestinal cells had no appreciable effects. Mechanistically, MS-444 disrupted HuR cytoplasmic trafficking and released ARE-mRNAs for localization to P-bodies, but did not affect total HuR expression levels. This resulted in MS-444-mediated inhibition of COX-2 and other ARE-mRNA expression levels. Importantly, MS-444 was well tolerated and inhibited xenograft CRC tumor growth through enhanced apoptosis and decreased angiogenesis upon intraperitoneal administration. In vivo treatment of MS-444 inhibited HuR cytoplasmic localization and decreased COX-2 expression in tumors. These findings provide evidence that therapeutic strategies to target HuR in CRC warrant further investigation in an effort to move this approach to the clinic. PMID- 27677076 TI - MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4. AB - MicroRNAs (miRs) are involved in the development and progression of hepatocellular carcinoma (HCC), but the regulatory mechanism of miR-98 in HCC still remains unclear. Here we found that miR-98 was significantly downregulated in HCC tissues compared to matched adjacent normal tissues (ANTs). Low miR-98 expression was associated with tumor size, metastasis, portal vein tumor embolus, and poor overall survival. Ectopic expression of miR-98 decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. SALL4 was identified as a novel target of miR-98, and the protein expression of SALL4 was inhibited by miR-98 in HCC cells. Overexpression of SALL4 reversed the suppressive effects of miR-98 on the malignant phenotypes of HCC cells. Besides, SALL4, upregulated in HCC tissues compared to the matched ANTs, was inversely correlated to the miR-98 levels in HCC tissues. In addition, overexpression of miR-98 markedly suppressed the tumor growth as well as tumor induced death in nude mice. In summary, miR-98 plays a suppressive role in the proliferation, migration, invasion and EMT of HCC cells, partly at least, via directly inhibition of SALL4. Therefore, the miR-98/SALL4 axis may become a promising therapeutic target for HCC. PMID- 27677078 TI - The pathological behaviors and prognostic factors of Chinese and Japanese colorectal cancers from general hospitals: a comparative study of the inpatients with surgical operation. AB - Here, we collected the information of 17304 and 2014 inpatients with colorectal cancer (CRC) from general hospitals of China and Japan respectively, and analyzed microscopic and macroscopic aspects, even stratified by the age and gender. It was found that Chinese CRC patients showed younger prone, more rectal and ascending cancers, less sigmoid and transverse cancers, larger size, less invasion into lymphatic system or metastasis into lymph node, and poorer differentiation than Japanese ones (p < 0.05). TNM staging was employed as an independent factor for the prognosis of the CRC patients regardless of the country (p < 0.05). Female patients showed larger tumor size, easier invasion and metastasis into lymphatic system, and worse differentiation than males (p < 0.05). The younger patients displayed frequent invasion and metastasis into lymphatic system, and poor differentiation in comparison to elder ones (p < 0.05). These findings demonstrated that Japanese patients seemed to have more invasion and metastasis due to standard and precise operation and pathological diagnosis accuracy. Actually, Chinese patients had more aggressive pathological characteristics and a poorer prognosis. Therefore, it is essential to establish a routine screening methodology, a standard treatment system and postoperative diagnosis protocol for the prevention and therapeutics of Chinese CRC patients, especially for female and young patients. PMID- 27677079 TI - Effects of in vitro and in vivo avermectin exposure on alpha synuclein expression and proteasomal activity in pigeons. AB - Avermectins (AVMs) are used worldwide in agriculture and veterinary medicine. Residues of avermectin drugs, causing toxicological effects on non-target organisms, have raised great concern. The aim of this study was to investigate the effects of AVM on the expression levels of alpha synuclein (alpha-Syn) and proteasomal activity in pigeon (Columba livia) neurons both in vivo and in vitro. The results showed that, the mRNA and protein levels of alpha-Syn increased in AVM treated groups relative to control groups in the cerebrum, cerebellum and optic lobe in vivo. Dose-dependent decreases in the proteasomal activity (i.e., chymotrypsin-like, trypsin-like and peptidylglutamyl peptidehydrolase) were observed both in vivo and in vitro. The results suggested that AVM could induce the expression levels of alpha-Syn and inhibit the normal physiological function of proteasome in brain tissues and neurons. The information presented in this study is helpful to understand the mechanism of AVM-induced neurotoxicology in birds. PMID- 27677077 TI - Single nucleotide polymorphisms in microRNA genes are associated with cervical cancer susceptibility in a population from Xinjiang Uygur. AB - The goal of this study was to explore the correlation between single nucleotide polymorphisms (SNPs) and susceptibility to cervical cancer (CC) in a population from Xinjiang Uygur. Participating were 247 patients with CC and 285 healthy women. Fourteen SNPs in nine miRNA genes were selected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to assess the correlation of SNPs with CC. The minor allele "C" of rs300574 in SPRY1 was associated with an increased risk of CC based on analysis of the allele, codominant, recessive and log-additive models, but an opposite result was found with the over-dominant model. The minor allele "C" of rs1042725 in HMGA2 was associated with an increased risk of CC in the allele, dominant and log-additive models. In clinical stage III/IVCC patients, rs4728 in SPRY2 was associated with decreased risk. Finally, rs3744935 in BCL2 was associated with CC in the allele and codominant models. In sum, we have detected associations between four SNPs, rs300574 (SPRY1), rs3744935 (BCL2), rs1042725 (HMGA2), and rs4728 (SPRY2), and CC risk in women from Xinjiang Uygur. PMID- 27677080 TI - The growth and uptake of Ga and In of rice (Oryza sative L.) seedlings as affected by Ga and In concentrations in hydroponic cultures. AB - Limited information is available on the effects of gallium (Ga) and indium (In) on the growth of paddy rice. The Ga and In are emerging contaminants and widely used in high-tech industries nowadays. Understanding the toxicity and accumulation of Ga and In by rice plants is important for reducing the effect on rice production and exposure risk to human by rice consumption. Therefore, this study investigates the effect of Ga and In on the growth of rice seedlings and examines the accumulation and distribution of those elements in plant tissues. Hydroponic cultures were conducted in phytotron glasshouse with controlled temperature and relative humidity conditions, and the rice seedlings were treated with different levels of Ga and In in the nutrient solutions. The growth index and the concentrations of Ga and In in roots and shoots of rice seedlings were measured after harvesting. A significant increase in growth index with increasing Ga concentrations in culture solutions (<10mgGaL-1) was observed. In addition, the uptake of N, K, Mg, Ca, Mn by rice plants was also enhanced by Ga. However, the growth inhibition were observed while the In concentrations higher than 0.08mgL-1, and the nutrients accumulated in rice plants were also significant decreased after In treatments. Based on the dose-response curve, we observed that the EC10 (effective concentration resulting in 10% growth inhibition) value for In treatment was 0.17mgL-1. The results of plant analysis indicated that the roots were the dominant sink of Ga and In in rice seedlings, and it was also found that the capability of translocation of Ga from roots to shoots were higher than In. In addition, it was also found that the PT10 (threshold concentration of phytotoxicity resulting in 10% growth retardation) values based on shoot height and total biomass for In were 15.4 and 10.6MUgplant-1, respectively. The beneficial effects on the plant growth of rice seedlings were found by the addition of Ga in culture solutions. In contrast, the In treatments led to growth inhibition of rice seedlings. There were differences in the phytotoxicity, uptake, and translocation of the two emerging contaminants in rice seedlings. PMID- 27677082 TI - Podocyte and Parietal Epithelial Cell Interactions in Health and Disease. AB - The glomerulus has 3 resident cells namely mesangial cells that produce the mesangial matrix, endothelial cells that line the glomerular capillaries, and podocytes that cover the outer surface of the glomerular basement membrane. Parietal epithelial cells (PrECs), which line the Bowman's capsule are not part of the glomerular tuft but may have an important role in the normal function of the glomerulus. A significant progress has been made in recent years regarding our understanding of the role and function of these cells in normal kidney and in kidneys with various types of glomerulopathy. In crescentic glomerulonephritis necrotizing injury of the glomerular tuft results in activation and leakage of fibrinogen which provides the trigger for excessive proliferation of PrECs giving rise to glomerular crescents. In cases of collapsing glomerulopathy, podocyte injury causes collapse of the glomerular capillaries and activation and proliferation of PrECs, which accumulate within the urinary space in the form of pseudocrescents. Many of the noninflammatory glomerular lesions such as focal segmental glomerulosclerosis and global glomerulosclerosis also result from podocyte injury which causes variable loss of podocytes. In these cases podocyte injury leads to activation of PrECs that extend on to the glomerular tuft where they cause segmental and/or global sclerosis by producing excess matrix, resulting in obliteration of the capillary lumina. In diabetic nephropathy, in addition to increased matrix production in the mesangium and glomerular basement membranes, increased loss of podocytes is an important determinant of long-term prognosis. Contrary to prior belief there is no convincing evidence for an active podocyte proliferation in any of the above mentioned glomerulopathies. PMID- 27677081 TI - The Effect of Active versus Passive Recovery Periods during High Intensity Intermittent Exercise on Local Tissue Oxygenation in 18 - 30 Year Old Sedentary Men. AB - PURPOSE: High intensity interval training (HIIT) has been proposed as a time efficient format of exercise to reduce the chronic disease burden associated with sedentary behaviour. Changes in oxygen utilisation at the local tissue level during an acute session of HIIT could be the primary stimulus for the health benefits associated with this format of exercise. The recovery periods of HIIT effect the physiological responses that occur during the session. It was hypothesised that in sedentary individuals, local and systemic oxygen utilisation would be higher during HIIT interspersed with active recovery periods, when compared to passive recovery periods. METHODS: Twelve sedentary males (mean +/- SD; age 23 +/- 3 yr) completed three conditions on a cycle ergometer: 1) HIIT with passive recovery periods between four bouts (HIITPASS) 2) HIIT with active recovery periods between four bouts (HIITACT) 3) HIITACT with four HIIT bouts replaced with passive periods (REC). Deoxygenated haemoglobin (HHb) in the vastus lateralis (VL) and gastrocnemius (GN) muscles and the pre-frontal cortex (FH), oxygen consumption (VO2), power output and heart rate (HR) were measured continuously during the three conditions. RESULTS: There was a significant increase in HHb at VL during bouts 2 (p = 0.017), 3 (p = 0.035) and 4 (p = 0.035) in HIITACT, compared to HIITPASS. Mean power output was significantly lower in HIITACT, compared to HIITPASS (p < 0.001). There was a significant main effect for site in both HIITPASS (p = 0.029) and HIITACT (p = 0.005). There were no significant differences in VO2 and HR between HIITPASS and HIITACT. CONCLUSIONS: The increase in HHb at VL and the lower mean power output during HIITACT could indicate that a higher level of deoxygenation contributes to decreased mechanical power in sedentary participants. The significant differences in HHb between sites indicates the specificity of oxygen utilisation. PMID- 27677083 TI - Starry Sky Pattern in Hematopoietic Neoplasms: A Review of Pathophysiology and Differential Diagnosis. AB - The starry sky pattern is a distinctive histologic feature wherein a rapidly proliferating hematolymphoid neoplasm contains scattered histiocytes with abundant pale cytoplasm in a background of monomorphic neoplastic cells. The cytoplasm of these histiocytes typically contains cellular remnants, also known as tingible bodies, incorporated through active phagocytosis. Although common and widely recognized, relatively little is known about the pathophysiological underpinnings of the starry sky pattern. Its resemblance to a similar pattern seen in the germinal centers of secondary follicles suggests a possible starting point for understanding the molecular basis of the starry sky pattern and potential routes for its exploitation for therapeutic purposes. In this review, we discuss the historical, pathophysiological, and clinical implications of the starry sky pattern. PMID- 27677084 TI - Improving Research into Models of Maternity Care to Inform Decision Making. AB - In a Perspective, Ank de Jonge and Jane Sandall discuss research on models of maternity care led by midwives. PMID- 27677085 TI - Predicting Fluid Responsiveness Using Bedside Ultrasound Measurements of the Inferior Vena Cava and Physician Gestalt in the Emergency Department of an Urban Public Hospital in Sub-Saharan Africa. AB - BACKGROUND: Bedside inferior vena cava (IVC) ultrasound has been proposed as a non-invasive measure of volume status. We compared ultrasound measurements of the caval index (CI) and physician gestalt to predict blood pressure response in patients requiring intravenous fluid resuscitation. METHODS: This was a prospective study of adult emergency department patients requiring fluid resuscitation. A structured data sheet was used to record serial vital signs and the treating clinician's impression of patient volume status and cause of hypotension. Bedside ultrasound CI measurements were performed at baseline and after each 500mL of fluid. Receiver operating characteristic (ROC) curve analysis was performed to characterize the relationship between CI and Physician gestalt, and the change in mean arterial pressure (MAP). RESULTS: We enrolled 364 patients, 52% male, mean age 36 years. Indications for fluid resuscitation were haemorrhage (54%), dehydration (30%), and sepsis (17%). Receiver operating characteristic curve analysis found optimal CI cut-off values of 45%, 52% and 53% to predict a MAP rise of 5, 8 and 10 mmHg per litre of fluid, respectively. The sensitivity and specificity of CI of 50% for predicting a 10mmHg increase in MAP per litre were 88% (95%CI 81-93%) and 73% (95%CI 67-79%), respectively, area under the curve (AUC) = 0.85 (0.81-0.89). The sensitivity and specificity of physician gestalt estimate of volume depletion severity were 68% (95%CI 60-75%) and 86% (95%CI 80-90%), respectively, AUC = 0.83 (95% CI: 0.79-0.87). Those with a baseline CI >= 50% (51% of patients) had a 2.8-fold greater fluid responsiveness than those with a baseline CI<50% (p<0.0001). CONCLUSION: Ultrasound measurement of the CI can predict blood pressure response among patients requiring intravenous fluid resuscitation and may be useful in early identification of patients who will benefit most from volume resuscitation, and those who will likely require other interventions. PMID- 27677088 TI - Bilateral internal thoracic artery graft configuration and coronary artery bypass grafting conduits. AB - PURPOSE OF REVIEW: Bilateral internal thoracic arteries (BITAs) have demonstrated their superiority over all other types of graft in terms of patency and survival benefit. BITA implementation requires the surgeon's evaluation of the patient's coronary anatomy and demographics. There is no single ideal approach to BITA utilization, but instead a variety of configurations that can be implemented based on the patient characteristics. RECENT FINDINGS: This article details the advantages and disadvantages of several BITA configurations in the setting of left-sided myocardial revascularization and right-sided myocardial revascularization. Different BITA configurations will be described and will ultimately serve as a guide to avoiding technical difficulties and helping surgeons construct decision-making trees to direct the implementation of BITA grafts. SUMMARY: BITA grafting provides long-term clinical benefit over conventional grafting. Efforts should be directed toward a more efficient use of internal thoracic arteries, reducing the need for a third complementary graft, and toward identification of the best alternative to the saphenous vein graft as the third graft material for complete revascularization. Surgeons should ask their cardiologists to be as accurate as possible regarding the severity of the coronary lesion. If the severity of the lesion is not obvious upon an informal qualitative assessment, a functional flow reserve of the lesion should be performed, in order to identify the optimal graft. PMID- 27677086 TI - [Comparison of ultrasound guided femoral and sciatic nerve block versus epidural anaesthesia for orthopaedic surgery in dogs]. AB - OBJECTIVE: Comparison of ultrasound-guided femoral and sciatic nerve block versus epidural anaesthesia with bupivacaine and morphine for orthopaedic surgery of the pelvic limb in dogs with respect to analgesic effectiveness, clinical utility and side effects. MATERIAL AND METHODS: The study included 22 dogs (American Society of Anesthesiologists, ASA grades I and II) undergoing orthopaedic surgery distal to the mid-femoral bone. The study was designed as a randomized, prospective, blinded clinical trial. All dogs were randomly assigned to receive 0.5 mg/kg bupivacaine (0.5%) and 0.1 mg/kg morphine sulphate (1%) either as epidural anaesthesia (group EPI) or by ultrasound-guided femoral and sciatic nerve block (group LA). During surgery, the heart rate, respiratory rate, mean arterial pressure (MAP), end-tidal isoflurane concentrations and dose of rescue analgesia (fentanyl boluses of 5 ug/kg i. v.) were measured. Pain severity was scored (short form of the Glasgow Composite Measure Pain Scale, GCMPS) before surgery and postoperatively at 2, 4, 6, 12 and 24 hours after extubation. Post-operative rescue analgesia consisted of methadone (0.2 mg/kg i. v.), and was applied when the GCMPS > 6. For statistical analysis, the Chi-square, Fisher, and Wilcoxon tests and one- and two-way ANOVA were applied. Differences were considered statistically significant at p < 0.05. RESULTS: Only the MAP was significantly different between the two treatment groups. Intra- and postoperative MAP of group LA (111.2 +/- 11.2 mmHg and 119.3 +/- 18.2 mmHg, respectively) was higher than in group EPI (86.6 +/- 8.7 mmHg and 95.2 +/- 13.1 mmHg, respectively). None of the dogs developed urinary retention or ambulatory deficits when completely recovered from anaesthesia. No other side effects were noted. CLINICAL RELEVANCE: In conclusion, femoral and sciatic nerve blocks and epidural anaesthesia ensure comparable analgesic effects in canine patients undergoing orthopaedic surgery of the pelvic limb. The lower mean arterial blood pressure of group EPI was not of clinical relevance. PMID- 27677089 TI - Difficult management in parathyroid carcinoma with synchronous parathyroid hyperplasia. PMID- 27677090 TI - Red Light-Dose or Wavelength-Dependent Photoresponse of Antioxidants in Herb Microgreens. AB - The purpose of this study was to evaluate the role of 638-nm and 665-nm LEDs on changes of antioxidants of basil (Ocimum basilicum) and parsley (Petroselinum crispum), and to assess the effect of light quality on antioxidative status. Plants were grown in peat substrate for 19 days (21/17 +/-2 degrees C, 16 h). Experiments were performed in (I) a controlled-environment: B455,R638,R665,FR731(control); B455,R*638,R665,FR731; B455,R638,R*665,FR731; R638; R665 (B-blue, R- red, FR-far-red light). PPFD was set from 231 during growth, upto 300 MUmol m-2 s-1 during 3-day treatment changing R638 or R665 PPFD level; in (II) greenhouse (November): high-pressure sodium lamps (HPS) (control 300 MUmol m-2s-1); and HPS + 638 (HPS generated 90 and red LEDs-210 MUmol m-2s 1). In general, under supplemental or increased red 638 nm light, amounts of tested antioxidants were greater in basil, whereas sole 665 nm or sole 638 nm is more favourable for parsley. Increased or supplemental red light significantly increased contents of phenolics, alpha-tocopherol, ascorbic acid and DPPH* but suppressed accumulation of lutein and beta-carotene in basil, whereas an increase of beta-carotene and DPPH* was observed in parsley. Hereby, the photoresponse of antioxidant compounds suggests that photoprotective mechanism is stimulated by both light-dose-dependent and wavelength-dependent reactions. PMID- 27677091 TI - Erratum. PMID- 27677092 TI - Skin mast cell phenotypes between two highly divergent cohorts - more pronounced variability within than between groups. PMID- 27677093 TI - Hypothalamic-Pituitary-Adrenocortical Dysfunction in Elderly, Male Marathon Runners: Feedback Sensitivity, Stress Response, and Effects on Verbal Memory. AB - Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system at a suprapituitary level, and to impaired mnemonic function. We compared cognitive tests, as well as feedback integrity and stress responsivity of the HPA system, between 11 elderly, male marathon runners - a model of repeated HPA system activation - and 10 sedentary controls. The marathon runners had significantly increased baseline, stress, and post-stress ACTH - but not cortisol - concentrations. Also, suppression of ACTH by 3 mg dexamethasone was impaired in the athletes compared to the control subjects, while the ACTH and cortisol response to additional CRH did not differ between the 2 groups. Finally, long term verbal memory was impaired in the athletes compared to the controls. Regarding the HPA system, these findings are in accordance with an acquired suprapituitary feedback disturbance in marathon runners; however, the similar glucocorticoid concentrations in the 2 groups may be due to reduced adrenal sensitivity to ACTH. Together with impaired verbal memory, these data support the assumption that repeated episodes of HPA system activity may exert negative effects at the level of the hippocampus. PMID- 27677094 TI - Controlling Proton Delivery through Catalyst Structural Dynamics. AB - The fastest synthetic molecular catalysts for H2 production and oxidation emulate components of the active site of hydrogenases. The critical role of controlled structural dynamics is recognized for many enzymes, including hydrogenases, but is largely neglected in designing synthetic catalysts. Our results demonstrate the impact of controlling structural dynamics on H2 production rates for [Ni(PPh2 NC6H4R2 )2 ]2+ catalysts (R=n-hexyl, n-decyl, n-tetradecyl, n-octadecyl, phenyl, or cyclohexyl). The turnover frequencies correlate inversely with the rates of chair-boat ring inversion of the ligand, since this dynamic process governs protonation at either catalytically productive or non-productive sites. These results demonstrate that the dynamic processes involved in proton delivery can be controlled through modification of the outer coordination sphere, in a manner similar to the role of the protein architecture in many enzymes. As a design parameter, controlling structural dynamics can increase H2 production rates by three orders of magnitude with a minimal increase in overpotential. PMID- 27677095 TI - PET-positive lymphadenopathy in CLL-Not always Richter transformation. PMID- 27677096 TI - The Institution of a Standardized Investigation Protocol for Sudden Infant Death in the Eastern Metropole, Cape Town, South Africa,. AB - The rate for the sudden infant death syndrome (SIDS) in Cape Town, South Africa, is estimated to be among the highest in the world (3.41/1000 live births). In several of these areas, including those of extreme poverty, only sporadic, nonstandardized infant autopsy, and death scene investigation (DSI) occurred. In this report, we detail a feasibility project comprising 18 autopsied infants with sudden and unexpected death whose causes of death were adjudicated according to the 1991 NICHD definitions (SIDS, n = 7; known cause of death, n = 7; and unclassified, n = 4). We instituted a standardized autopsy and infant DSI through a collaborative effort of local forensic pathology officers and clinical providers. The high standard of forensic investigation met international standards, identified preventable disease, and allowed for incorporation of research. We conclude that an effective infant autopsy and DSI protocol can be established in areas with both high sudden unexpected infant death, and elsewhere. (SUID)/SIDS risk and infrastructure challenges. PMID- 27677097 TI - Polydimethylsiloxane-coated partitioning sample collection device for the precise quantification of polycyclic aromatic hydrocarbons in air. AB - A novel partitioning collection device comprising a glass cartridge packed with poly(dimethylsiloxane)-coated macroporous silica particles was developed for the precise quantification of polycyclic aromatic hydrocarbons in air. The analyte collection and elution performances achieved using different amounts of poly(dimethylsiloxane) coating were quantitatively evaluated. The sample retention power increased with increasing the coating, and more than 250 L of air could be collected without analyte breakthrough at a sampling temperature of 35 degrees C. During the air collection, the moisture in the air was not retained on the particles due to the hydrophobic surface of the sorbent. A complete and rapid elution of the collected analytes from the device was accomplished by the passage of only 10 mL of acetone with ultrasonication for 1 min. The proposed method was successfully applied for the determination of airborne polycyclic aromatic hydrocarbons in tunnel air. PMID- 27677098 TI - Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN. AB - Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19-1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12 1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92-1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN. PMID- 27677099 TI - Glycosylation of monoclonal antibody products: Current status and future prospects. AB - Protein based therapeutics have started to dominate the pharmaceutical landscape primarily due to the high efficacy that they have demonstrated against complex diseases. Despite the significant success, issues with regards to safety, efficacy and quality of biotherapeutics have been a point of considerable debate and concern among the various stakeholders. The correlation between the glycoform profile and the safety and efficacy of a drug, in particular, has garnered significant attention of researchers worldwide. An escalated emphasis is presently given to develop an understanding of how the various process parameters as well molecular biology considerations contribute to glycan heterogeneity. This paper aims to review the major developments that have occurred in this area over the last decade. The impact of the various process parameters on glycan expression, methods for obtaining a pre-determined glycan levels/profiles of a protein therapeutic and developments in the area of real-time glycan monitoring and control are discussed. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1091-1102, 2016. PMID- 27677100 TI - Steroid vs. Platelet-Rich Plasma in Ultrasound-Guided Sacroiliac Joint Injection for Chronic Low Back Pain. AB - BACKGROUND: Despite widespread use of steroids to treat sacroiliac joint (SIJ) pain, their duration of pain reduction is short. Platelet-rich plasma (PRP) can potentially enhance tissue healing and may have a longer-lasting effect on pain. OBJECTIVES: To assess the efficacy and safety of PRP compared with methylprednisolone in ultrasound-guided SIJ injection for low back pain. STUDY DESIGN: Prospective randomized open blinded end point (PROBE) study. METHODS: Forty patients with chronic low back pain diagnosed with SIJ pathology were randomly allocated into 2 groups. Group S received 1.5 mL of methylprednisolone (40 mg/mL) and 1.5 mL of 2% lidocaine with 0.5 mL of saline, while Group P received 3 mL of leukocyte-free PRP with 0.5 mL of calcium chloride into ultrasound-guided SIJ injection. Visual analog scale (VAS) scores, Modified Oswestry Disability Questionnaire (MODQ) scores, Short Form (SF-12) Health Survey scores, and complications (if any) were evaluated at 2 weeks, 4 weeks, 6 weeks, and 3 months. RESULTS: Intensity of pain was significantly lower in Group P at 6 weeks (median [interquartile range (IQR)] = 1 [1 to 1] vs. 3.5 [2 to 5]; P = 0.0004) and 3 months (Median [IQR] = 1 [1 to 3] vs. 5 [3 to 5]; P = 0.0002) as compared to Group S. The efficacy of steroid injection was reduced to only 25% at 3 months in Group S, while it was 90% in Group P. A strong association was observed in patients receiving PRP and showing a reduction of VAS >= 50% from baseline when other factors were controlled. The MODQ and SF-12 scores were improved initially for up to 4 weeks but deteriorated further at 3 months in Group S, while both the scores improved gradually for up to 3 months in Group P. CONCLUSION: The intra-articular PRP injection is an effective treatment modality in low back pain involving SIJ. PMID- 27677101 TI - Fiber type composition of pubococcygeus and bulbospongiosus striated muscles is modified by multiparity in the rabbit. AB - AIMS: We analyzed the effect of multiparity on the fiber type composition of two skeletal muscles involved in the maintenance of the micturition process, the pelvic pubococcygeus (Pc) and perineal bulbospongiosus (Bs) muscles in nulliparous and multiparous rabbits (Oryctolagus cuniculus). METHODS: We used the basic ATPase and NADH-TR techniques to identify and characterize slow, intermediate, and fast fiber types and glycolitic and oxidative fibers in muscles, respectively. RESULTS: Pc muscles of multiparous rabbits present relatively high percentages of slow and intermediate fibers but a low percentage of fast fibers (P < 0.05) as compared to Pc muscles from nulliparous rabbits, while percentages of glycolytic and oxidative fibers were similar (P > 0.05). Bs muscles of multiparous rabbits had a higher proportion of intermediate and glycolytic fibers (P < 0.05) than muscles of nulliparous. Both, Pc and Bs muscles of nulliparous and multiparous rabbits contain slow fibers with similar large cross sectional area, but fast fibers in multiparous muscles showed small cross sectional area than in nulliparous. CONCLUSIONS: Multiparity modified the fiber type composition of Pc and Bs muscles in female rabbits. We propose that the contractile force and the physiological role of both muscles during micturition are affected because of the observed changes in the relative composition of muscle fiber types. PMID- 27677103 TI - [MR-imaging findings in Epstein-Barr virus encephalitis]. PMID- 27677102 TI - National Glucose-Lowering Treatment Complexity Is Greater in Nursing Home Residents than Community-Dwelling Adults. PMID- 27677104 TI - ? PMID- 27677105 TI - ? PMID- 27677106 TI - ? PMID- 27677107 TI - ? PMID- 27677108 TI - ? PMID- 27677109 TI - ? PMID- 27677110 TI - ? PMID- 27677111 TI - ? PMID- 27677112 TI - ? PMID- 27677113 TI - Synchronous male breast and colon cancer presenting with ileus: A case report. AB - INTRODUCTION: Cancer developing from more than one origin is called multiple primary cancer (MPC) and is a rare situation. In this article, we report a case presenting to the Emergency Clinic with symptoms of ileus who was diagnosed with synchronous colon and breast cancer. PRESENTATION OF CASE: A 57year old male patient presented to the Emergency Clinic with abdominal pain, vomiting, constipation and lack of flatulence. The patient was taken to the operating room for emergency surgery with the diagnosis of intestinal obstruction. While still hospitalized, breast ultrasound was performed, revealing a mass lesion in the right breast measuring 2cm. The core biopsy result was suggestive of invasive ductal adenocarcinoma. Right modified radical mastectomy with removal of the level 2 axillary lymph nodes was performed. The result of the histopathological investigation of the right hemicolectomy specimen was reported as moderately differentiated adenocarcinoma, while that of the mastectomy material was invasive ductal adenocarcinoma. DISCUSSION: Synchronous colorectal cancer is recognized as an important clinical entity, its clinical and pathological properties as well as prognosis are still undetermined. A family history of cancer might be a significant factor in synchronous cancers. Many of the theories about the etiology of multiple primary malignant neoplasia suggest the role of genetic, hormonal, environmental and immunological factors as well as iatrogenic causes. CONCLUSION: Especially for patients whose treatment begins in the emergency settings, meticulous systemic physical examination is recommended to initiate treatment of a possible synchronous tumor at an earlier stage. PMID- 27677114 TI - Laparoscopic extra-abdominal suturing technique for the repair of Larrey's diaphragmatic hernia using the port closure needle (Endo Close(r)): A case report. AB - INTRODUCTION: Morgagni's or Larrey's diaphragmatic hernias are relatively uncommon. If the defect is too large for primary closure, the use of a mesh is inevitable. Although primary closure is adaptable for relatively small defects, it is difficult to suture the hernial orifice in which the anterior rim is absent. Herein, we present the case of a patient with Larrey's diaphragmatic hernia that was easily and securely repaired using the recently developed laparoscopic extra-abdominal suturing technique via the port closure needle (Endo Close(r); Medtronic, Minneapolis, USA). PRESENTATION OF CASE: An 89-year-old woman complaining of vomiting was transferred to our hospital. Computed tomography scan showed Larrey's diaphragmatic hernia. Laparoscopic repair was performed after gastric decompression. We diagnosed Larrey's hernia on the left side of the falciform ligament. The transverse colon was herniated through the defect. Since the hernial defect was located below the substernal space, there was no tissue to stitch at the anterior rim of the hernial orifice. We performed the extra-abdominal suturing technique, suturing the posterior rim of the hernia to the full thickness of the anterior abdominal wall using the port closure needle (Endo Close(r)) without the need for a mesh. The patient was discharged on the 8th postoperative day. There was no evidence of recurrence at 8 months postoperatively. DISCUSSION: The recently developed extra-abdominal suturing technique using Endo Close(r) to suture the full thickness of the anterior abdominal wall achieved secure mattress suture and easy extra-abdominal tying. CONCLUSION: This method may be useful in terms of easiness and security of suture. PMID- 27677116 TI - Ulcerated choledochocele: A case report. AB - BACKGROUND: The cystic dilatation of the biliary tract is an uncommon anomaly. Choledochocele, a cystic dilatation of the distal common bile duct, rarely presents clinically as massive gastrointestinal bleeding. AIM: This is to report a very rare disease condition and highlight minimal access options in surgical care. CASE SUMMARY: A 13 year-old boy was referred with a day history of sudden onset of passage of bright red blood per rectum with a fainting episode. There was no anal protrusion, jaundice, recurrent epigastric pain nor bleeding from any other orifice. An initial endoscopic assessment of the upper digestive tract showed profuse bleeding from a sub-mucosal mass in the region of ampulla of Vater. Emergency laparotomy revealed small intestine filled with blood from duodenum to ileum. A duodenotomy showed a cystic mass with an ulcerated mucosa at the dome containing bilious fluid in the second part of the duodenum. The cyst was de-roofed and marsupialized. Post-operative recovery was complicated by features of adhesive small bowel obstruction on the 9th post op day and treated by laparoscopic adhesiolysis. He was discharged home in good clinical state. CONCLUSION: Choledochocele is a differential diagnosis in the endoscopic finding of a submucosal mass in the second part of the duodenum. An initial oesophagogastroduodenoscopy endoscopy is necessary in the evaluation of massive lower gastrointestinal bleeding. PMID- 27677115 TI - Combined liver transplantation and sleeve gastrectomy for end-stage liver disease in a bariatric patient: First European case-report. AB - INTRODUCTION: Obesity is a contributor to the global burden of chronic diseases, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH). NASH cirrhosis is becoming a leading indication for liver transplant (LT). Obese transplanted patients have higher morbidity and mortality rates. One strategy, to improve the outcomes in these patients, includes bariatric surgery at the time of LT. Herein we report the first European combined LT and sleeve gastrectomy (SG). CASE PRESENTATION: A 53 years old woman with Hepatocellular carcinoma and Hepatitis C virus related cirrhosis, was referred to our unit. She also presented with severe morbid obesity (BMI 40kg/m2) and insulin-dependent diabetes. Once listed for LT, she was assessed by the bariatric surgery team to undergo a combined LT/SG. At the time of transplantation the patient had a model for end-stage liver disease calculated score of 14 and a BMI of 38kg/m2. The LT was performed using a deceased donor. An experienced bariatric surgeon, following completion of the LT, performed the SG. Operation time was 8h and 50min. The patient had an uneventful recovery and is currently alive, 5 months after the combined procedure, with normal allograft function, significant weight loss (BMI=29kg/m2), and diabetes resolution. CONCLUSION: Despite the ideal approach to the management of the obese LT patients remains unknown, we strongly support the combined procedure during LT in selected patients, offering advantages in terms of allograft and patient survival, maintenance of weigh loss that will ultimately reduce obese related co-morbidities. PMID- 27677117 TI - Theoretical investigation of low detection sensitivity for underivatized carbohydrates in ESI and MALDI. AB - Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mainly generate protonated ions from peptides and proteins but sodiated (or potassiated) ions from carbohydrates. The ion intensities of sodiated (or potassiated) carbohydrates generated by ESI and MALDI are generally lower than those of protonated peptides and proteins. Ab initio calculations and transition state theory were used to investigate the reasons for the low detection sensitivity for underivatized carbohydrates. We used glucose and cellobiose as examples and showed that the low detection sensitivity is partly attributable to the following factors. First, glucose exhibits a low proton affinity. Most protons generated by ESI or MALDI attach to water clusters and matrix molecules. Second, protonated glucose and cellobiose can easily undergo dehydration reactions. Third, the sodiation affinities of glucose and cellobiose are small. Some sodiated glucose and cellobiose dissociate into the sodium cations and neutral carbohydrates during ESI or MALDI process. The increase of detection sensitivity of carbohydrates in mass spectrometry by various methods can be rationalized according to these factors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27677118 TI - On the estimation errors of KM and V from time-course experiments using the Michaelis-Menten equation. AB - The conditions under which the Michaelis-Menten equation accurately captures the steady-state kinetics of a simple enzyme-catalyzed reaction is contrasted with the conditions under which the same equation can be used to estimate parameters, KM and V, from progress curve data. Validity of the underlying assumptions leading to the Michaelis-Menten equation are shown to be necessary, but not sufficient to guarantee accurate estimation of KM and V. Detailed error analysis and numerical "experiments" show the required experimental conditions for the independent estimation of both KM and V from progress curves. A timescale, tQ, measuring the portion of the time course over which the progress curve exhibits substantial curvature provides a novel criterion for accurate estimation of KM and V from a progress curve experiment. It is found that, if the initial substrate concentration is of the same order of magnitude as KM, the estimated values of the KM and V will correspond to their true values calculated from the microscopic rate constants of the corresponding mass-action system, only so long as the initial enzyme concentration is less than KM. PMID- 27677119 TI - A comparative study of microcystin-LR degradation by electrogenerated oxidants at BDD and MMO anodes. AB - This study investigated the electrochemical degradation of microcystin-LR (MC-LR) using boron-doped diamond (BDD) anode and mixed metal oxides (MMO, IrO2Ta2O5/Ti) anode in different medium. In-situ electrogenerated oxidants including hydroxyl radical, active chlorine, and persulfate were confirmed in phosphate, chloride, and sulfate medium, respectively. Different from MMO anode, hydroxyl radical was observed to play a significant role in chlorine generation at BDD anode in chloride medium. Besides, BDD anode could activate sulfate electrochemically due to its high oxygen evolution potential, and MC-LR degradation rate increased with the decrease of solution pH. The effects of natural organic matters (NOM) and algal organic matters (AOM) on MC-LR degradation were evaluated and NOM presented stronger inhibition ability than AOM. Furthermore, the intermediates generated in MC-LR degradation in chloride and sulfate medium were identified by LC/MS/MS and possible degradation pathways were proposed based on the experiments results. Benzene ring and conjugated diene bonds of Adda group and double bonds of Mhda group were found to be the reactive sites of MC-LR. Overall, this study broadens the knowledge of electrochemical oxidation in removing microcystins in algae laden water. PMID- 27677120 TI - The effects of arsenic contaminated drinking water of livestock on its total levels in milk samples of different cattle: Risk assessment in children. AB - This work was carried out to evaluate the arsenic (As) levels in milk samples of different milch animals, sheep, goats, cows, buffaloes and camels in Tharparkar, Pakistan. The concentration of As in the milk samples of cows, buffalos, sheep, goats and camels were observed in the range of 15.1-18.4, 2.6-7.7, 25.7-33.2, 10.5-37.3 and 6.6-13.7 MUg/L, respectively. The levels of As in livestock drinking water of each farms/flocks was found in the range of 238-2000 MUg L-1. A positive correlation with Pearson correlation coefficients, ranged as, 0.926 0.974 (p = 0.001-0.011) was observed between the As concentration in milk samples of cattle and in corresponding drinking water of farms/flocks. The high bio transfer factor of As was occurred in the milk samples of sheep. The content of As in scalp hair of children was observed to be elevated, who consumed milk of lower cattle (sheep and goat) than cow and camel. The As content in scalp hair directly proportional to the age of children. The hazardous quotient value of As due to consumption of milk was observed in decreasing order as, sheep > goats > camels > cows. The total hazardous quotient or noncarcinogenic risk values for children consuming the milk of sheep, goat, cow and camels were found >1 of reference dose for As, creates adverse effects on health in childhood stage. The children of all three age group have higher carcinogenic risk factor who are consuming milk of goat and sheep than larger cattle. PMID- 27677121 TI - Dissipation of pterosin B in acid soils - Tracking the fate of the bracken fern carcinogen ptaquiloside. AB - Bracken ferns (Pteridium spp.) are well-known for their carcinogenic properties, which are ascribed to the content of ptaquiloside and ptaquiloside-like substances. Ptaquiloside leach from the ferns and may cause contamination of drinking water. Pterosin B is formed by hydrolysis of ptaquiloside. In soil, Pterosin B is adsorbed more strongly and it is expected to have a slower turnover than ptaquiloside. We thus hypothesized that pterosin B may serve as an indicator for any past presence of ptaquiloside. Pterosin B degradation was studied in acid forest soils from bracken-covered and bracken-free areas. Soil samples were incubated with pterosin B at 3 and 8 MUg g-1 for 10 days, whereas sterile (autoclaved) samples were incubated for 23 days. Pterosin B showed unexpected fast degradation in soils with full degradation in topsoils in 2-5 days. Pterosin B dissipation followed the sum of two-first order reactions. The initial fast reaction with half-lives of 0.7-3.5 h contributed 11-59% of the total pterosin B degradation, while the slow reaction was 20-100 times slower than the fast reaction. Total dissipation half-lives were shorter for loamy sand (4 h) than for sandy loam soils (28 h). No degradation of pterosin B took place under sterile conditions assuming observed dissipation during the first 3 h could be attributed to irreversible sorption. Our results demonstrate that pterosin B is microbially degraded and that pterosin B is as unstable as ptaquiloside and hence cannot be used as an indicator for former presence of ptaquiloside in soil. PMID- 27677122 TI - A new extraction method to assess the environmental availability of ciprofloxacin in agricultural soils amended with exogenous organic matter. AB - Fluoroquinolone antibiotics such as ciprofloxacin can be found in soils receiving exogenous organic matter (EOM). Their long-term behavior in EOM-amended soils and their level of biodegradability are not well understood partly due to a lack of methods to estimate their environmental availability. We performed different aqueous extractions to quantify the available fraction of 14C-ciprofloxacin in soils amended with a compost of sewage sludge and green wastes or a farmyard manure contaminated at relevant environmental concentrations. After minimizing 14C-ciprofloxacin losses by adsorption on laboratory vessel tubes, three out of eleven different aqueous solutions were selected, i.e., Borax, Na2EDTA and 2 hydroxypropyl-beta-cyclodextrin. During 28 d of incubation, the non-extractable fractions were very high in all samples, i.e., 57-67% of the initial 14C activity, and the availability of the antibiotic was very low, explaining its low biodegradation. A maximum of 6.3% of the initial 14C-activity was extracted from soil/compost mixtures with the Na2EDTA solution, and 7.2% from soil/manure mixtures with the Borax solution. The available fraction level was stable over the incubation in soil/compost mixtures but slightly varied in soil/manure mixtures following the organic matter decomposition. The choice of different soft extractants highlighted different sorption mechanisms controlling the environmental availability of ciprofloxacin, where the pH and the quality of the applied EOM appeared to be determinant. PMID- 27677123 TI - Effect of silicate on arsenic fractionation in soils and its accumulation in rice plants. AB - Four rice genotypes, two hybrid and two indica, were selected to investigate the effects of silicate (Si) application on arsenic (As) accumulation and speciation in rice and As fractionation in soil. There were significant differences in root, straw and grain biomass among genotypes (p < 0.05), and Si application significantly increased root (p < 0.05) and grain biomass (p < 0.001). Silicate addition reduced the proportion of As associated with well-crystallized hydrous oxides of Fe and Al and residual phases, whilst increasing the proportions of specifically-sorbed As and As associated with amorphous and poorly-crystalline Fe and Al hydrous oxides. Furthermore, the results indicated that the fraction proportions of non-specifically sorbed, specifically-sorbed, and associated with amorphous and poorly-crystalline hydrous oxides of Fe and Al in rhizosphere soils, were greater than non-rhizosphere soils. Silicate application had a significant effect decreasing total As concentrations in root (p < 0.005), straw (p < 0.05) and husk (p < 0.001) of rice plants. The effect of Si on reducing As accumulation in rice leaves was revealed by SXRF. Indica genotypes transported and accumulated less As than hybrid genotypes. Both percentage and concentration of iAs were lower in indica genotype XFY-9 than in hybrid genotype XWX-12. Silicate reduced iAs and DMA by 21% and 58% in grain (polished) respectively. DMA may have a greater translocation capacity from straw to grain (polished) than inorganic As. The study provides the potential for understanding As uptake mechanisms in rice and mitigating the health risks posed by As contamination in paddy fields. PMID- 27677124 TI - Enhanced detoxification and degradation of herbicide atrazine by a group of O methyltransferases in rice. AB - Atrazine (ATR) as a toxic herbicide has become one of the seriously environmental contaminants worldwide due to its long-term intensive use in crop production. This study identified novel methyltransferases (MTs) involved in detoxification and degradation of ATR residues in rice plants. From a subset of MTs differentially expressed in ATR-exposed rice, forty-four O-methyltransferase genes were investigated. Total activities were significantly enhanced by ATR in rice tissues. To prove detoxifying capacity of the MTs in rice plants, two rice O MTs (LOC_Os04g09604 and LOC_Os11g15040) were selected and transformed into yeast cells (Pichia pastoris X-33). The positive transformants accumulated less ATR and showed less toxicity. Using UPLC-TOF-MS/MS, ATR-degraded products in rice and yeast cells were characterized. A novel O-methylated-modified metabolite (atraton) and six other ATR-derivatives were detected. The topological interaction between LOC_Os04g09604 enzyme and its substrate was specially analyzed by homology modeling programs, which was well confirmed by the molecular docking analysis. The significance of the study is to provide a better understanding of mechanisms for the specific detoxification and degradation of ATR residues in rice growing in environmentally relevant ATR-contaminated soils and may hold a potential engineering perspective for generating ATR-resistant rice that helps to minimize ATR residues in crops. PMID- 27677126 TI - Inhibition of Big-Conductance Ca2+-Activated K+ Channels in Vascular Myocytes Is a Key Novel Mechanism for Immunodepressant-Induced Hypertension. PMID- 27677125 TI - Effects of Alcohol Consumption on Left Ventricular Diastolic Function in Hypertensive Patients. PMID- 27677129 TI - Disclosure Index. PMID- 27677127 TI - Non-Invasive Imaging of Lung Remodeling and Right Ventricle Metabolic Shift in an Animal Model of Pulmonary Hypertension. PMID- 27677130 TI - Evaluation of Telmesartan Monotherapy on Morning Blood Pressure Surge in Patients with Mild to Moderate Hypertension. PMID- 27677131 TI - Nighttime Blood Pressure Measured with a Timer-Equipped Home Device - An Alternative to Nighttime Ambulatory Monitoring. PMID- 27677132 TI - Isolate Systolic Hypertension and Central Pressures in Elderly Patients. Differences Between Men and Women with Similar Peripheral Pressures. PMID- 27677133 TI - Secreted Monocyte miR-27a Causes Hypertension by Reducing Mas Receptor Expression and Function in the Artery. PMID- 27677134 TI - Role of GRK4 in the Regulation of Arterial AT1 Receptor in Hypertension. PMID- 27677135 TI - Plasma Enalapril Kinetics of Two Modified Formulations Tested in Healthy Volunteers. A Pilot Trial Searching for an Optimum Blood Pressure Control. PMID- 27677136 TI - Irisin Lowered Blood Pressure by Augmenting Acetylcholine-Mediated Vasodilation via AMPK-Akt-eNOS-NO Signal Pathway in the Spontaneously Hypertensive Rat. PMID- 27677137 TI - Loss of Adiponectin-Induced Renal Sodium Excretion in Hypertension. PMID- 27677138 TI - Limited Acceptance of Detailed Health Examination After Detection of Pathological Findings in Screening Test. PMID- 27677139 TI - RDN in Hypertensives: Results from a Novel Anatomical Approach. PMID- 27677140 TI - Prenatal Lipopolysaccharide Exposure Causes Mesenteric Vascular Dysfunction Through NO-cGMP Pathway in Offspring. PMID- 27677141 TI - Additivity of Nebivolol/Valsartan Single-Pill Combination Versus Other Single Pill Combinations for Hypertension. PMID- 27677142 TI - Systolic Blood Pressure as a Novel Determinant of Nocturia in Non-Hispanic Black Men. PMID- 27677143 TI - Prevalence of Eligibility Criteria for the Systolic Blood Pressure Intervention Trial in US Adults Among Excluded Groups: Age <50 Years, Diabetes, or a History of Stroke. PMID- 27677144 TI - Masked and Nocturnal Hypertension in the ARTS-DN ABPM Sub-Study with Finerenone. PMID- 27677145 TI - Transcriptional Gene Silencing of Dopamine D3 Receptor Caused by Let-7d Mimics in Immortalized Renal Proximal Tubule Cells of Rats. PMID- 27677146 TI - The Effects of Nebivolol-Valsartan Single-Pill Combinations in Reducing Blood Pressure in Patients with Stage I or II Hypertension. PMID- 27677147 TI - First Latin American Experience with the Renal Denervation VESSIX(r) System: Promising Data at 12 Months Follow Up. PMID- 27677148 TI - Activated Intrarenal Renin Angiotensin Systems Is the Primary Source of Progressing Renal Damage in Primary Aldosteronism. PMID- 27677149 TI - Elevated Blood Pressure in the Emergency Department: How Well Do Emergency Physicians Treat, Inform and Refer Their Hypertensive Patients Based on Chief Complaint? PMID- 27677150 TI - pH-controlled doxorubicin anticancer loading and release from carbon nanotube noncovalently modified by chitosan: MD simulations. AB - In the present study, we describe here the pH condition activating doxorubicin (DOX) anticancer drugs loading and release over single-wall carbon nanotube (SWNT) non-covalently wrapped with chitosan (CS). The possibility of drug displacement on DOX/CS/SWNT nanocarrier was investigated using molecular dynamics simulations. The drug loading and release were monitored via displacement analysis and binding energy calculations. The simulated results clearly showed that the drugs well interacted with the CS/SWNT at physiological pH (pH 7.4), where CS was in the deprotonated form. Contrastingly, in weakly acidic environments (pH 5.0-6.5) which is a pH characteristics of certain cancer environments, the protonated CS became loosen wrapped around the SWNT and triggered drugs release as a result of charge-charge repulsion between CS and drug molecules. The obtained data fulfil the understanding at atomic level of drug loading and release controlled by pH-sensitive polymer, which might be useful for further cancer therapy researches. PMID- 27677151 TI - In-situ biogas upgrading in thermophilic granular UASB reactor: key factors affecting the hydrogen mass transfer rate. AB - Biological biogas upgrading coupling CO2 with external H2 to form biomethane opens new avenues for sustainable biofuel production. For developing this technology, efficient H2 to liquid transfer is fundamental. This study proposes an innovative setup for in-situ biogas upgrading converting the CO2 in the biogas into CH4, via hydrogenotrophic methanogenesis. The setup consisted of a granular reactor connected to a separate chamber, where H2 was injected. Different packing materials (rashig rings and alumina ceramic sponge) were tested to increase gas liquid mass transfer. This aspect was optimized by liquid and gas recirculation and chamber configuration. It was shown that by distributing H2 through a metallic diffuser followed by ceramic sponge in a separate chamber, having a volume of 25% of the reactor, and by applying a mild gas recirculation, CO2 content in the biogas dropped from 42 to 10% and the final biogas was upgraded from 58 to 82% CH4 content. PMID- 27677152 TI - CO2 capture using limestone for cultivation of the freshwater microalga Chlorella sorokiniana PAZ and the cyanobacterium Arthrospira sp. VSJ. AB - The present study reports a process wherein CO2 is captured in the form of bicarbonates using calcium oxide and photosynthetically fixed into biomass. Microalgal cultures viz. Chlorella sorokiniana PAZ and Arthrospira sp. VSJ were grown in the medium containing bicarbonates. The rate of bicarbonate utilization by C. sorokiniana PAZ was higher when CO2 trapped in the presence of 2.67mM calcium oxide than in the presence of 10mM sodium hydroxide and with direct addition of 10mM sodium bicarbonate. For Arthrospira sp. VSJ the bicarbonate utilization was 92.37%, 88.34% and 59.23% for the medium containing CaO, NaOH and NaHCO3, respectively. Illumination of photosynthetically active radiation (PAR)+ultraviolet A radiation (UVA) enhanced the yield of C. sorokiniana PAZ and Arthrospira sp. VSJ by 1.3 and 1.8 folds, respectively. FTIR analysis revealed elevation in the biosynthesis of specific metabolites in response to the UVA exposure. PMID- 27677153 TI - Carbon spectrum utilization by an indigenous strain of Pseudomonas aeruginosa NCIM 5514: Production, characterization and surface active properties of biosurfactant. AB - The present research work was undertaken with a mandate to study carbon spectrum utilization and structural characterization of biosurfactant produced by indigenous Pseudomonas aeruginosa NCIM 5514, which showed unique properties to utilize a large number of carbon sources effectively for production of biosurfactant, although glucose was the best carbon substrate. In Bushnell-Hass medium supplemented with glucose (1%, w/v), 3.178+/-0.071g/l biosurfactant was produced by this isolate in 96h. The biosurfactant produced showed surface tension and emulsification activity values from 29.14+/-0.05 to 62.29+/-0.13mN/m and 88.50+/-1.96 to 15.40+/-0.91%, respectively. Toluene showed highest emulsification activity followed by kerosene. However, kerosene exhibited emulsion stability for 30days. Biosurfactant was characterized as a mixture of di rhamnolipid (Rha-Rha-C10-C14:1) and mono-rhamnolipid (Rha-C8-C10) by FTIR, ESI-MS and LC-MS techniques. High biosurfactant yield opens up doors for the isolate to find utility in various industries. PMID- 27677154 TI - Immobilization of Carbonylcobalt Catalyst by Poly(4-vinylpyridine) (P4VP) through N->Co Coordination Bonds: The Promotional Effect of Pyridine and the Reusability of Polymer Catalyst. AB - A carbonylcobalt catalyst, immobilized by poly(4-vinylpyridine) (P4VP) through N >Co coordination bonds, has been prepared by solvothermal method. It has been revealed that the pyridine fragments in the polymer catalyst act not only as promoters to improve the catalytic performance of the carbonylcobalt catalyst for alkoxycarbonylation of ethylene oxide to methyl 3-hydroxypropanoate but also as stabilizers to enhance the reusability of the polymer catalyst. Furthermore, the polymer catalyst could be easily separated by filtration and reused with only a slight loss of catalytic efficiency. PMID- 27677155 TI - Changes in expression of genes involved in antitumor immunity in mice vaccinated with tumor vaccine composed of irradiated syngeneic tumor cells and CpG oligodeoxynucleotides. AB - In our previous studies, it has been demonstrated that in more than 80% of mice long-lasting antitumor immunity has been established following intraperitoneal (i.p.) vaccination with tumor vaccine composed of irradiated syngeneic tumor cells and CpG ODNs class C. The aim of this study was, therefore, to investigate molecular mechanisms through which this vaccine triggers the immunity and to define genes particularly involved in this process. Changes in gene expression were followed in mononuclear cells isolated from peritoneal lavages, spleens and bone marrow samples. The expression of 84 genes significant for T-cell and B-cell activation as well as genes engaged in activation of macrophages, NK cells and DCs was determined using the RT2- Profiler PCR array. It has been observed that this tumor vaccine induces the up-regulation of genes involved in activation, proliferation and survival of memory T-cells (Cd8a, Cd8b1, Prlr, Was, Cxcl12, Il12, Sftpd, Tnfrsf13c, Il15, Il18), and prevents the activation of genes involved in generation of Treg and induction of immune tolerance (Sit1, Sla2, Cd1d1, Pdcd1lg2, Pawr, Socs5, Il27, Il4). We may conclude based on results of gene expression analysis, that tumor vaccine fine-tunes the proportion of cytotoxic to regulatory lymphocytes having an important impact on the induction and maintenance of memory cells in bone marrow. PMID- 27677156 TI - CD4+ T cells require either B cells or CD8+ T cells to control spread and pathogenesis of a neurotropic infection. AB - Immunity within the brain, specifically to virus-infected neurons, must be controlled to prevent neuron loss and impairment, though the process by which this occurs remains unclear. Here, we use a mouse model of neuron-restricted measles virus infection, in which immunocompetent adults survive challenge, whereas T and B cell-deficient mice succumb. This model allowed us to more precisely define the contributions of CD4+ T cells, CD8+ T cells, and B cells in neuroprotection. Both B cell knockout mice and mice depleted of CD8+ T cells survive challenge and show no signs of illness, though are less able to control viral replication than immunocompetent mice. In contrast, depletion of CD4+ T cells results in disease and death in all infected mice, though the kinetics of illness are delayed compared to RAG knockout mice. Our data suggest a coordinated interplay of adaptive immune components, which collectively controls viral spread and limits neuropathogenesis. PMID- 27677157 TI - Novel Endorna-like viruses, including three with two open reading frames, challenge the membership criteria and taxonomy of the Endornaviridae. AB - Viruses associated with wild orchids and their mycorrhizal fungi are poorly studied. Using a shotgun sequencing approach, we identified eight novel endornavirus-like genome sequences from isolates of Ceratobasidium fungi isolated from pelotons within root cortical cells of wild indigenous orchid species Microtis media, Pterostylis sanguinea and an undetermined species of Pterostylis in Western Australia. They represent the first endornaviruses to be described from orchid mycorrhizal fungi and from the Australian continent. Five of the novel endornaviruses were detected from one Ceratobasidium isolate collected from one Pterostylis plant. The partial and complete viral replicases shared low (9 30%) identities with one another and with endornaviruses described from elsewhere. Four had genome lengths greater than those of previously described endornaviruses, two resembled ascomycete-infecting endornaviruses, and unlike currently described endornaviruses, three had two open reading frames. The unusual features of these new viruses challenge current taxonomic criteria for membership of the family Endornaviridae. PMID- 27677159 TI - Increasing prevalence of K65K and K66K in HIV-1 subtype B reverse transcriptase. AB - OBJECTIVE: Synonymous substitutions K65K/K66K in HIV-1 reverse transcriptase alleviate fitness and fidelity defects in HIV-1 molecular clones harboring thymidine analogue mutations (TAMs); however, their potential for transmission and persistence is unknown. Here, we investigated the temporal appearance of K65K/K66K relative to TAMs in a HIV-1 cohort, their prevalence over time, and their impact on viral fitness in the context of patient-derived reverse transcriptase sequences. METHODS: Retrospective analyses of the temporal appearance and longitudinal prevalence of synonymous substitutions and drug resistance mutations were performed using the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program (DTP) database. Plasma-derived HIV 1 from the DTP was used to generate infectious molecular clones. Growth competition assays were performed to determine viral fitness. RESULTS: The prevalence of K65K/K66K in drug-naive individuals tripled from 11% in 1997 to 37% in 2014 (P < 0.0001, n = 5221), with K66K mainly accounting for the increase. These mutations emerged in drug-treated individuals without TAMs in 14% of the cohort and conferred a fitness advantage in the context of patient-derived multidrug-resistant (MDR) virus in the absence of drug. CONCLUSION: The appearance of K65K/K66K in drug-treated individuals was largely independent of TAMs, suggesting alternative factors are likely associated with their emergence. The increasing K65K/K66K prevalence to over a third of treatment-naive individuals in the mostly subtype B DTP cohort and their ability to confer a fitness advantage to multidrug-resistant virus might explain the transmission and persistence of virus harbouring K65K/K66K in untreated individuals, and highlights their role in adaptive HIV-1 evolution. PMID- 27677160 TI - Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix). AB - BACKGROUND: The development of a prophylactic vaccine against HIV-1 has so far not been successful. Therefore, attention has shifted more and more toward the development of novel therapeutic vaccines. Here, we evaluated a new mRNA-based therapeutic vaccine against HIV-1-encoding activation signals (TriMix: CD40L + CD70 + caTLR4) combined with rationally selected antigenic sequences [HIVACAT T cell immunogen (HTI)] sequence: comprises 16 joined fragments from Gag, Pol, Vif, and Nef). METHODS: For this purpose, peripheral blood mononuclear cells from HIV 1-infected individuals on cART, lymph node explants from noninfected humans, and splenocytes from immunized mice were collected and several immune functions were measured. RESULTS: Electroporation of immature monocyte-derived dendritic cells from HIV-infected patients with mRNA encoding HTI + TriMix potently activated dendritic cells which resulted in upregulation of maturation markers and cytokine production and T-cell stimulation, as evidenced by enhanced proliferation and cytokine secretion (IFN-gamma). Responses were HIV specific and were predominantly targeted against the sequences included in HTI. These findings were confirmed in human lymph node explants exposed to HTI + TriMix mRNA. Intranodal immunizations with HTI mRNA in a mouse model increased antigen-specific cytotoxic T-lymphocyte responses. The addition of TriMix further enhanced cytotoxic responses. CONCLUSION: Our results suggest that uptake of mRNA, encoding strong activation signals and a potent HIV antigen, confers a T-cell stimulatory capacity to dendritic cells and enhances their ability to stimulate antigen specific immunity. These findings may pave the way for therapeutic HIV vaccine strategies based on antigen-encoding RNA to specifically target antigen presenting cells. PMID- 27677162 TI - Immune tolerance properties of the testicular tissue as a viral sanctuary site in ART-treated HIV-infected adults. AB - OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically privileged compartment. We assessed immunotolerance properties of the testicular tissue in individuals receiving suppressive antiretroviral therapy (ART). DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from six virally suppressed adults and 10 HIV-uninfected controls prior to sex reassignment surgery. T cells were purified from freshly isolated testicular interstitial cell suspensions. T-cell subsets, expression of immune activation markers and HIV DNA were assessed in matched testicular cells and peripheral blood mononuclear cells (PBMCs). RESULTS: When compared with PBMCs, testes were characterized by a lower CD4 T-cell proportion among total T cells, a decrease in the frequency of naive cells, an increase in the frequency of effector-memory T cells and an increase in CCR5 expression in both the HIV+ and HIV- groups. In HIV infected individuals on ART, testes displayed higher T-cell immune activation (Coexpression of CD38 and Human Leukocyte Antigen - antigen D Related) than PBMCs. In both groups, testes were characterized by higher frequencies of immunosuppressive CD39 regulatory T cells and a massive increase in CD73 expression on CD8 T cells. In addition, a remarkable increase in indoleamine pyrrole 2,3-dioxygenase immunosuppressive enzyme involved in tryptophan/kynurenine catabolism was observed in testes versus blood. Rare cells harboring HIV DNA were detected in testes from five out six participants. CONCLUSION: These findings suggest that the adenosine and tryptophan/kynurenine immune-metabolic pathways contribute to immune tolerance in testicular tissue. Our results suggest that testes may represent a distinctive HIV sanctuary site during ART. PMID- 27677161 TI - Topical gentian violet compared with nystatin oral suspension for the treatment of oropharyngeal candidiasis in HIV-1-infected participants. AB - OBJECTIVE: Compare the safety and efficacy of topical gentian violet with that of nystatin oral suspension (NYS) for the treatment of oropharyngeal candidiasis in HIV-1-infected adults in resource-limited settings. DESIGN: Multicenter, open label, evaluator-blinded, randomized clinical trial at eight international sites, within the AIDS Clinical Trials Group. STUDY PARTICIPANTS AND INTERVENTION: Adult HIV-infected participants with oropharyngeal candidiasis, stratified by CD4 cell counts and antiretroviral therapy status at study entry, were randomized to receive either gentian violet (0.00165%, BID) or NYS (500 000 units, QID) for 14 days. MAIN OUTCOME MEASURE(S): Cure or improvement after 14 days of treatment. Signs and symptoms of oropharyngeal candidiasis were evaluated in an evaluator blinded manner. RESULTS: The study was closed early per Data Safety Monitoring Board after enrolling 221 participants (target = 494). Among the 182 participants eligible for efficacy analysis, 63 (68.5%) in the gentian violet arm had cure or improvement of oropharyngeal candidiasis versus 61 (67.8%) in the NYS arm, resulting in a nonsizable difference of 0.007 (95% confidence interval: -0.129, 0.143). There was no sizable difference in cure rates between the two arms ( 0.0007; 95% confidence interval: -0.146, 0.131). No gentian violet-related adverse events were noted. No sizable differences were identified in tolerance, adherence, quality of life, or acceptability of study drugs. In gentian violet arm, 61 and 39% of participants reported 'no' and 'mild-to-moderate' staining, respectively. Cost for medication procurement was significantly lower for gentian violet versus NYS (median $2.51 and 19.42, respectively, P = 0.01). CONCLUSION: Efficacy of gentian violet was not statistically different than NYS, was well tolerated, and its procurement cost was substantially less than NYS. PMID- 27677165 TI - The association between HIV, antiretroviral therapy, and gestational diabetes mellitus. AB - OBJECTIVES: The widespread, chronic use of antiretroviral therapy raises questions concerning the metabolic consequences of HIV infection and treatment. Antiretroviral therapy, and specifically protease inhibitors, has been associated with hyperglycemia. As pregnant women are vulnerable to development of hyperglycemia, the objective of this study was to explore existing literature on the relationship between HIV infection, HIV treatment, and gestational diabetes mellitus (GDM). METHODS: A systematic search was conducted in six databases for articles providing data on HIV-positivity, protease inhibitor exposure, and GDM or glucose intolerance development in pregnancy. The quality of articles was evaluated using an adapted Cochrane Collaboration bias assessment tool. Risk ratios were generated from pooled data using meta-analysis by the Mantel-Haenszel method. RESULTS: Of 891 references screened, six studies on the role of HIV positivity, 10 on protease inhibitor use, and two on both were included. Meta analysis showed no significant relationship between HIV infection and the development of GDM [risk ratio 0.80, 95% confidence interval (CI): 0.47-1.37, I = 0%]. Meta-analysis of protease inhibitor exposure showed increased GDM in studies using first-generation protease inhibitors (risk ratio 2.29, 95% CI: 1.46-3.58) and studies using the strictest diagnosis criteria, the National Diabetes Data Group criteria for 3-h oral glucose tolerance test (risk ratio 3.81, 95% CI: 2.18 6.67). CONCLUSION: Meta-analysis showed no significant association between HIV positivity and GDM. Significance of protease inhibitor use was limited to studies using the strictest diagnostic criteria for GDM. Results are limited by high risk of bias. Well designed prospective studies are needed to further clarify this relationship and its consequences for clinical practice. PMID- 27677163 TI - Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern. AB - OBJECTIVE: To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania. DESIGN: Prospective cohort study with cross sectional analysis. METHODS: All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM. RESULTS: Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART associated DRM were identified in 90%, with multiclass resistances in 79%. Pre ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11-13.68], female sex (aOR = 2.57; 95% CI 1.03-6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51 35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4 T-cell percentage (aOR = 0.20; 0.10-0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73-0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure. CONCLUSION: Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV. PMID- 27677166 TI - Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection. AB - OBJECTIVE: Liver disease markers have been associated with mortality in HIV infected individuals in the modern era of effective antiretroviral therapy. Our objective was to determine which markers are most predictive of mortality in HIV monoinfected and HIV/hepatitis C virus (HCV)-coinfected persons. RESEARCH DESIGN AND METHODS: We measured serum albumin, total protein, calculated globulin, aspartate transaminase (AST), and alanine transaminase in 193 HIV/HCV-coinfected and 720 HIV-monoinfected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection. We evaluated associations of each marker with 5-year, all-cause mortality, adjusting for cardiovascular, HIV-related factors, inflammation, renal disease, muscle, and adiposity. RESULTS: After 5 years of follow-up, overall mortality was 21% in HIV/HCV-coinfected and 12% in HIV monoinfected participants. After multivariable adjustment, lower albumin and higher AST were independently associated with increased mortality. Lower albumin was associated with 49% increased odds of mortality overall [per 0.5 g/dl decrease, 95% confidence interval (CI): 1.2-1.9]; the association was stronger in HIV/HCV-coinfected [odds ratio (OR) = 2.1, 95% CI: 1.4-3.2] vs. HIV-monoinfected (OR = 1.3, 95% CI: 1.0-1.7; HCV-by-albumin interaction: P = 0.038). Higher AST was associated with 41% increased odds of mortality (per AST doubling; 95% CI: 1.1-1.8); associations were much stronger among HIV/HCV-coinfected (OR = 2.5, 95% CI: 1.5-4.1) than HIV-monoinfected (OR = 1.1, 95% CI: 0.8-1.5; HCV-by-AST interaction: P = 0.0042). CONCLUSION: Lower serum albumin and higher AST appear to be important mortality risk factors in HIV/HCV-coinfection, but much less so in HIV-monoinfected individuals. The association of low albumin with mortality may reflect its role as a negative acute phase response protein. AST levels do not appear to be useful in predicting mortality in HIV-monoinfection and should be considered primarily in the context of HCV-coinfection. PMID- 27677167 TI - Hydroxytyrosol: a new class of microbicide displaying broad anti-HIV-1 activity. AB - OBJECTIVE: To investigate the toxicity and activity against HIV of 5 hydroxytyrosol as a potential microbicide. DESIGN: The anti-HIV-1 activity of 5 hydroxytyrosol, a polyphenolic compound, was tested against wild-type HIV-1 and viral clones resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors and integrase inhibitors. In addition to its activity against founder viruses, different viral subtypes and potential synergy with tenofovir disoproxil fumarate, lamivudine and emtricitabine was also tested. 5-Hydroxytyrosol toxicity was evaluated in vivo in rabbit vaginal mucosa. METHODS: We have cloned pol gene from drug-resistant HIV-1 isolated from infected patients and env gene from Fiebeg III/IV patients or A, C, D, E, F and G subtypes in the NL4.3-Ren backbone. 5-Hydroxytyrosol anti-HIV-1 activity was evaluated in infections of MT-2, U87 CCR5 or peripheral blood mononuclear cells preactivated with phytohemagglutinin + interleukin-2 with viruses obtained through 293T transfections. Inhibitory concentration 50% and cytotoxic concentration 50% were calculated. Synergy was analysed according to Chou and Talalay method. In-vivo toxicity was evaluated for 14 days in rabbit vaginal mucosa. RESULTS: 5-Hydroxytyrosol inhibited HIV-1 infections of recombinant or wild-type viruses in all the target cells tested. Moreover, 5-hydroxytyrosol showed similar inhibitory concentration 50% values for infections with NRTIs, NNRTIs, protease inhibitors and INIs resistant viruses; founder viruses and all the subtypes tested. Combination of 5-hydroxytyrosol with tenofovir was found to be synergistic, whereas it was additive with lamivudine and emtricitabine. In-vivo toxicity of 5-hydroxytyrosol was very low even at the highest tested doses. CONCLUSION: 5-Hydroxytyrosol displayed a broad anti-HIV-1 activity in different cells systems in the absent of in-vivo toxicity, therefore supporting its candidacy as a potential new class of microbicides. PMID- 27677168 TI - Effects of depression and anxiety on antiretroviral therapy adherence among newly diagnosed HIV-infected Chinese MSM. AB - OBJECTIVE: Our objective was to explore the effect of depression and anxiety on adherence to antiretroviral therapy (ART) among MSM with newly diagnosed HIV infections. DESIGN: We conducted a prospective study of Chinese MSM with newly diagnosed HIV infections. METHODS: The Hospital Anxiety and Depression Scale was used to measure depression and anxiety at baseline, 6 and 12 months, separately. ART adherence was self-reported once every 3 months ('perfect' or no missing dose in the past 3 months vs. 'imperfect' adherence or at least one missing dose in the past 3 months). We utilized a priori substantial knowledge guided by causal models to identify confounding covariates, and performed mixed-effect logistic regression to assess the effects of depression and anxiety on ART adherence. RESULTS: We included 228 participants who initiated ART after HIV diagnosis and before the end of study. A one-unit increase in the depression and anxiety score was associated with a 16% increase [adjusted odds ratio (aOR), 1.16; 95% confidence interval (CI), 1.02-1.32] and a 17% increase (aOR, 1.17; 95% CI, 1.03 1.33) in the odds of reporting imperfect ART adherence, respectively. When depression and anxiety were categorized (normal, borderline, and likely), only likely anxiety had a significant association with imperfect ART adherence (aOR, 4.79; 95% CI, 1.12-20.50). CONCLUSION: Depression and anxiety are risk factors for imperfect ART adherence among Chinese MSM with newly diagnosed HIV infections. Intensive intervention on depression and/or anxiety beyond regular post-HIV-testing counseling may increase adherence to ART, and improve HIV treatment outcomes. PMID- 27677170 TI - Effects of breast density and compression on normal breast tissue hemodynamics through breast tomosynthesis guided near-infrared spectral tomography. AB - Optically derived tissue properties across a range of breast densities and the effects of breast compression on estimates of hemoglobin, oxygen metabolism, and water and lipid concentrations were obtained from a coregistered imaging system that integrates near-infrared spectral tomography (NIRST) with digital breast tomosynthesis (DBT). Image data were analyzed from 27 women who underwent four IRB approved NIRST/DBT exams that included fully and mildly compressed breast acquisitions in two projections-craniocaudal (CC) and mediolateral-oblique (MLO) and generated four data sets per patient (full and moderate compression in CC and MLO views). Breast density was correlated with HbT (r=0.64, p=0.001), water (r=0.62, p=0.003), and lipid concentrations (r=?0.74, p<0.001), but not oxygen saturation. CC and MLO views were correlated for individual subjects and demonstrated no statistically significant differences in grouped analysis. Comparison of compressed and uncompressed imaging demonstrated a significant decrease in oxygen saturation under compression (58% versus 50%, p=0.04). Mammographic breast density categorization was correlated with measured optically derived properties. PMID- 27677172 TI - Genome-Wide Association Study of HIV Whole Genome Sequences Validated using Drug Resistance. AB - BACKGROUND: Genome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics. METHOD: We performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naive to the respective treatment. RESULTS: GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting GWAS's ability to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR. CONCLUSIONS: These results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS. PMID- 27677174 TI - TraqBio - Flexible Progress Tracking for Core Unit Projects. AB - MOTIVATION: Core service units have become an organisational hallmark in many research institutions world wide. Such service cores provide complex state-of-the art technologies and expertise to the research community. Typically, a user delivers material or raw data to a core. The core defines work packages for ensuing analysis and returns results back to the user. This core activity can be quite complex and time consuming and usually does not communicate itself to the outside. Naturally, the user is highly interested to follow the progress of a project once handed over to the core unit. This generates a time-intensive direct communication activity back and forth. A more effective, convenient and less disruptive way to track the status of a given project by the researcher, but also by core managers, appears highly desirable. Hence, we developed a lightweight and readily implementable web application that allows efficient progress tracking of core unit projects. RESULTS: The web application TraqBio allows for the convenient tracking of projects. Following project set-up by the core, the user receives an e-mail containing links for tracking the project status. Examples are provided for three common core units, namely genomics, proteomics, and bioinformatics units. TraqBio is a secure lightweight web application that can be either used in a standalone setup or incorporated into an existing web server infrastructure. Being accessible not only from classical desktop computers but also from mobile devices such as smartphones and tablets, TraqBio offers easy integration into every day work. PMID- 27677171 TI - In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state. AB - Populations in developed nations throughout the world are rapidly aging, and the search for geroprotectors, or anti-aging interventions, has never been more important. Yet while hundreds of geroprotectors have extended lifespan in animal models, none have yet been approved for widespread use in humans. GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition. Known substances are then screened and ranked for those most likely to target differential pathways and mimic the young signalome. Here we used GeroScope and shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. This work not only highlights several potential geroprotectors for further study, but also serves as a proof-of-concept for GeroScope, Oncofinder and other PAS-based methods in streamlining drug prediction, repurposing and personalized medicine. PMID- 27677176 TI - Successful Delivery in a 39-Year-Old Patient with Anal Cancer after Fertility Preserving Surgery Followed by Primary Chemoradiation and Low Anti-Mullerian Hormone Level. AB - Anal cancer was diagnosed in a 36-year-old nulliparous woman. Before chemoradiation was started, ovarian transposition and uterine fixation were performed in order to preserve capability for future parenthood. Despite of a low anti-Mullerian hormone level, IVF therapy was successful and resulted in a full term delivery of a healthy baby by cesarean section. This is the first case report of successful pregnancy after full-dose pelvic radiation for anal cancer. PMID- 27677175 TI - Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice. AB - INTRODUCTION: The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin-induced fibrosis in mice of a Th2-dominant immune background (BALB/c). METHODS: BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). RESULTS: At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1; p<0.01), (IL-1beta; p<0.001), (IL-5; p<0.01), (IL-6; p<0.001), (IL-13; p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). CONCLUSION: AE attenuated bleomycin induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model. PMID- 27677177 TI - Laboratory Monitoring of Oral Vitamin K Anticoagulation. AB - Vitamin K antagonists (VKA) have been used for many years as effective anticoagulant therapy. The laboratory plays a crucial role in measuring the prothrombin time (PT) and calculating the international normalized ratio (INR). Each component of the calculation has the potential to increase error in the final result. This article discusses the laboratory aspects of monitoring VKA including sample requirements, PT, determination of the INR, point of care (POC) testing, external quality assurance/proficiency testing, and reversal strategies for VKA therapy. The implementation of the PT/INR reporting standard was a significant improvement in laboratory medicine. However, further room for improvement exists in the management of PT/INR testing, to clarify the role of POC testing and continue the harmonization process to ensure reliability and reproducibility of INR results. PMID- 27677173 TI - Sex-Biased Transcriptome of Schistosoma mansoni: Host-Parasite Interaction, Genetic Determinants and Epigenetic Regulators Are Associated with Sexual Differentiation. AB - BACKGROUND: Among more than 20,000 species of hermaphroditic trematodes, Schistosomatidae are unusual since they have evolved gonochorism. In schistosomes, sex is determined by a female heterogametic system, but phenotypic sexual dimorphism appears only after infection of the vertebrate definitive host. The completion of gonad maturation occurs even later, after pairing. To date, the molecular mechanisms that trigger the sexual differentiation in these species remain unknown, and in vivo studies on the developing schistosomulum stages are lacking. To study the molecular basis of sex determination and sexual differentiation in schistosomes, we investigated the whole transcriptome of the human parasite Schistosoma mansoni in a stage- and sex-comparative manner. METHODOLOGY/ PRINCIPAL FINDINGS: We performed a RNA-seq on males and females for five developmental stages: cercariae larvae, three in vivo schistosomulum stages and adults. We detected 7,168 genes differentially expressed between sexes in at least one of the developmental stages, and 4,065 of them were functionally annotated. Transcriptome data were completed with H3K27me3 histone modification analysis using ChIP-Seq before (in cercariae) and after (in adults) the phenotypic sexual dimorphism appearance. In this paper we present (i) candidate determinants of the sexual differentiation, (ii) sex-biased players of the interaction with the vertebrate host, and (iii) different dynamic of the H3K27me3 histone mark between sexes as an illustration of sex-biased epigenetic landscapes. CONCLUSIONS/ SIGNIFICANCE: Our work presents evidence that sexual differentiation in S. mansoni is accompanied by distinct male and female transcriptional landscapes of known players of the host-parasite crosstalk, genetic determinants and epigenetic regulators. Our results suggest that such combination could lead to the optimized sexual dimorphism of this parasitic species. As S. mansoni is pathogenic for humans, this study represents a promising source of therapeutic targets, providing not only data on the parasite development in interaction with its vertebrate host, but also new insights on its reproductive function. PMID- 27677178 TI - Plasmin: A Modulator of Immune Function. AB - Plasmin is the effector protease of the fibrinolytic system, well known for its involvement in fibrin degradation and clot removal. However, plasmin is also recognized as a potent modulator of immunological processes by directly interacting with various cell types including leukocytes (monocytes, macrophages, and dendritic cells) and cells of the vasculature (endothelial cells, smooth muscle cells) as well as soluble factors of the immune system and components of the extracellular matrix. In fact, the removal of misfolded proteins and maintenance of tissue homeostasis seem to be major physiological functions of plasmin. However, a large body of evidence also suggests that excessive plasmin generation frequently contributes to the pathophysiology of acute and chronic inflammatory processes. Hence, one question arising from the broadening effects of plasmin in physiology is whether antifibrinolytic drugs (i.e., tranexamic acid, epsilon aminocaproic acid, or aprotinin) that target plasmin either directly or indirectly and which are commonly used to prevent or treat bleeding might have unintended consequences on the immune response or on other nonfibrinolytic processes in vivo. PMID- 27677180 TI - Letter to the Editor. PMID- 27677181 TI - Older Adults of Underrepresented Populations and Their End-of-Life Preferences: An Integrative Review. AB - This integrative review was conducted to examine the evidence for understanding diversity in end-of-life preferences among older adults of underrepresented groups. Findings from 21 studies were critically examined, grouped, and compared across studies, populations, and settings. Five major themes emerged: advance directives, hospice and palliative care, communication, knowledge and information, and home and family. Despite multidisciplinary attention, content and methodological limitations narrowed understanding of what matters most to these groups when making decisions at end of life. Rigorous longitudinal studies with more ethnically diverse samples are needed to detect modifiable factors related to disparities at the end of life. PMID- 27677179 TI - tPA Modulation of the Blood-Brain Barrier: A Unifying Explanation for the Pleiotropic Effects of tPA in the CNS. AB - The plasminogen activation (PA) system is best known for its role in fibrinolysis. However, it has also been shown to regulate many nonfibrinolytic functions in the central nervous system (CNS). In particular, tissue-type plasminogen activator (tPA) is reported to have pleiotropic activities in the CNS, regulating events such as neuronal plasticity, excitotoxicity, and cerebrovascular barrier integrity, whereas urokinase-type plasminogen activator is mainly associated with tissue remodeling and cell migration. It has been suggested that the role tPA plays in controlling barrier integrity may provide a unifying mechanism for the reported diverse, and often opposing, functions ascribed to tPA in the CNS. Here we will review the possibility that the pleiotropic effects reported for tPA in physiologic and pathologic processes in the CNS may be a consequence of its role in the neurovascular unit in regulation of cerebrovascular responses and subsequently parenchymal homeostasis. We propose that this might offer an explanation for the ongoing debate regarding the neurotoxic versus neuroprotective roles of tPA. PMID- 27677182 TI - The Role of Serum MicroRNA-6767-5p as a Biomarker for the Diagnosis of Polycystic Ovary Syndrome. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, and the underlying molecular mechanisms are not clear. To date, few studies have been conducted on the altered expression of serum microRNAs (miRNAs) in women with PCOS. The present study was performed to examine the role of the serum miRNA as a biomarker for the diagnosis of PCOS and its relationship with metabolic and reproductive traits. METHODS: A cross-sectional comparison was made in 21 women with PCOS and age- and body mass index (BMI)- matched 21 healthy women in an academic center laboratory between December 2008 and October 2010. We selected miRNAs that were more than 1.5-fold up-regulated or less than 0.67-fold down regulated in women with PCOS compared with controls using the SurePrint G3 Human miRNA Microarray. Subsequently, we validated the relative expression of the miRNAs using TaqMan quantitative real-time polymerase chain reaction (RT-qPCR) assays. RESULTS: Serum miRNA-4522, miRNA-324-3p, and miRNA-6767-5p were down regulated in women with PCOS compared with controls in the microarray analysis. Among these miRNAs, serum miRNA-6767-5p was validated (fold change in women with PCOS/controls = 0.39, P-value<0.05) by RT-qPCR. The miRNA-6767-5p was negatively associated with fasting glucose (beta = -0.370) and positively associated with the number of menses per year (beta = 0.383) after adjustment for age and BMI (Ps<0.05). Genes targeted by miRNA-6767-5p were involved in the cell cycle and the immune system. CONCLUSIONS: Serum miRNA-6767-5p may be a novel candidate as a molecular biomarker in the diagnosis of PCOS and may participate in the development of the metabolic and reproductive traits of PCOS. PMID- 27677183 TI - Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children. AB - BACKGROUND: Major gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the binding specificity of five members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, PvRBP2-P2 and a non-binding fragment of PvRBP2c) to normocytes or reticulocytes. PvRBP2b was identified as the only reticulocyte-specific binder (P<0.001), whereas the others preferentially bound to normocytes (PvRBP1a/b P<=0.034), or showed comparable binding to both (PvRBP2a/2-P2, P = 0.38). Furthermore, we measured levels of total and IgG subclasses 1, 2, 3 and 4 to the six PvRBPs in a cohort of young Papua New Guinean children, and assessed their relationship with prospective risk of P. vivax malaria. Children had substantial, highly correlated (rho = 0.49 0.82, P<0.001) antibody levels to all six PvRBPs, with dominant IgG1 and IgG3 subclasses. Both total IgG (Incidence Rate Ratio [IRR] 0.63-0.73, P = 0.008 0.041) and IgG1 (IRR 0.56-0.69, P = 0.001-0.035) to PvRBP2b and PvRBP1a were strongly associated with reduced risk of vivax-malaria, independently of age and exposure. CONCLUSION/SIGNIFICANCE: These results demonstrate a diversity of erythrocyte-binding phenotypes of PvRBPs, indicating binding to both reticulocyte specific and normocyte-specific ligands. Our findings provide further insights into the naturally acquired immunity to P. vivax and highlight the importance of PvRBP proteins as targets of naturally acquired humoral immunity. In-depth studies of the role of PvRBPs in P. vivax invasion and functional validation of the role of anti-PvRBP antibodies in clinical immunity against P. vivax are now required to confirm the potential of the reticulocyte-binding PvRBP2b and PvRBP1a as vaccine candidate antigens. PMID- 27677184 TI - A Positive Selection for Nucleoside Kinases in E. coli. AB - Engineering heterologous nucleoside kinases inside E. coli is a difficult process due to the integral role nucleosides play in cell division and transcription. Nucleoside analogs are used in many kinase screens that depend on cellular metabolization of the analogs. However, metabolic activation of these analogs can be toxic through disruptions of DNA replication and transcription because of the analogs' structural similarities to native nucleosides. Furthermore, the activity of engineered kinases can be masked by endogenous kinases in the cytoplasm, which leads to more difficulties in assessing target activity. A positive selection method that can discern a heterologous kinases' enzymatic activity without significantly influencing the cell's normal metabolic systems would be beneficial. We have developed a means to select for a nucleoside kinase's activity by transporting the kinase to the periplasmic space of an E. coli strain that has its PhoA alkaline phosphatase knocked out. Our proof-of-principle studies demonstrate that the herpes simplex virus thymidine kinase (HSV-TK) can be transported to the periplasmic space in functional form by attaching a tat signal sequence to the N-terminus of the protein. HSV-TK phosphorylates the toxic nucleoside analog 3'-azido-3'-deoxythymidine (AZT), and this charged, monophosphate form of AZT cannot cross the inner membrane. The translocation of HSV-TK provides significant resistance to AZT when compared to bacteria lacking a periplasmic HSV-TK. However, resistance decreased dramatically above 40 MUg/ml AZT. We propose that this threshold can be used to select for higher activity variants of HSV-TK and other nucleoside kinases in a manner that overcomes the efficiency and localization issues of previous selection schemes. Furthermore, our selection strategy should be a general strategy to select or evaluate nucleoside kinases that phosphorylate nucleosides such as prodrugs that would otherwise be toxic to E. coli. PMID- 27677186 TI - Putative Tumor Suppressor Genes EGR1 and BRSK1 Are Mutated in Gastric and Colorectal Cancers. AB - OBJECTIVE: The transcription factor-encoding EGR1 and the kinase-encoding BRSK1 are considered putative tumor suppressor genes (TSGs). However, EGR1 and BRSK1 mutations that could inactivate their functions are not reported in colorectal (CRC) and gastric (GC) cancers. METHODS: There are mononucleotide repeats in EGR1 and BRSK1, which could be mutated in cancers with defects in mismatch repair, resulting in microsatellite instability (MSI). We analyzed 124 CRCs and 79 GCs for mutations and their intratumoral heterogeneities (ITHs). RESULTS: Twenty-one out of 79 CRCs (26.6%) and 5 out of 34 GCs (14.7%) carrying high MSI (MSI-H) exhibited frameshift mutations. However, we found no such mutations in cancers with microsatellite stability. In addition, we studied ITH for these mutations in 16 cases of CRCs and observed that EGR1 and BRSK1 mutations exhibited ITH in 3 (18.8%) and 2 (12.5%) cases, respectively. CONCLUSION: Our data in this study reveal that the TSG genes EGR1 and BRSK1 carry mutational ITH as well as frameshift mutations in MSI-H CRC and GC, which together may be features of GC and CRC with MSI-H. These results suggest that frameshift mutations of EGR1 and BRSK1 might play a role in tumorigenesis through TSG inactivation in CRC and GC. PMID- 27677185 TI - Lipoic Acid Use and Functional Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke and Diabetes. AB - BACKGROUND: Alpha-lipoic acid (aLA) is a strong antioxidant commonly used for treating diabetic polyneuropathy. Previously, we demonstrated the neurorestorative effects of aLA after cerebral ischemia in rats. However, its effects on patients with stroke remain unknown. We investigated whether patients treated with aLA have better functional outcomes after acute ischemic stroke (AIS) and reperfusion therapy than patients not receiving aLA. METHODS: In this retrospective study of 172 prospectively registered patients with diabetes and AIS treated with tissue plasminogen activator (tPA), we investigated the relationship between aLA use and functional outcome both after 3 months and after 1 year. The functional outcomes included occurrence of hemorrhagic transformation (HT), early neurological deterioration (END), and early clinical improvement (ECI). Favorable outcomes were defined as modified Rankin Scale (mRS) scores of 0 2. RESULTS: Of the 172 patients with AIS and diabetes, 47 (27.3%) used aLA. In the entire cohort, favorable outcomes occurred at significantly higher rates both at 3 months and at 1 year in those treated with aLA. The risks for END and HT were lower and the occurrence of ECI was higher in patients treated with aLA. In multivariable analysis, aLA use was associated with favorable outcomes both at 3 months and at 1 year. Age, HT, and increased National Institutes of Health Stroke Scale scores were negative predictors of a favorable outcome. CONCLUSIONS: The use of aLA in patients with AIS and diabetes who are treated with tPA is associated with favorable outcomes. These results indicate that aLA could be a useful intervention for the treatment of AIS after reperfusion therapy. PMID- 27677187 TI - Bioinspired decision architectures containing host and microbiome processing units. AB - Biomimetic robots have been used to explore and explain natural phenomena ranging from the coordination of ants to the locomotion of lizards. Here, we developed a series of decision architectures inspired by the information exchange between a host organism and its microbiome. We first modeled the biochemical exchanges of a population of synthetically engineered E. coli. We then built a physical, differential drive robot that contained an integrated, onboard computer vision system. A relay was established between the simulated population of cells and the robot's microcontroller. By placing the robot within a target-containing a two dimensional arena, we explored how different aspects of the simulated cells and the robot's microcontroller could be integrated to form hybrid decision architectures. We found that distinct decision architectures allow for us to develop models of computation with specific strengths such as runtime efficiency or minimal memory allocation. Taken together, our hybrid decision architectures provide a new strategy for developing bioinspired control systems that integrate both living and nonliving components. PMID- 27677189 TI - The need for a long-term multidisciplinary follow-up in the management of mTBI. PMID- 27677188 TI - Canine scent detection for the diagnosis of lung cancer in a screening-like situation. AB - The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respectively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers. PMID- 27677190 TI - Pharmacokinetic drug evaluation of albutrepenonacog alfa (CSL654) for the treatment of hemophilia. AB - INTRODUCTION: Replacement therapy for FVIII/IX in hemophilia A/B is more than 50 years old following the discovery of cryoprecipitate by Judith Pool in 1964. On demand therapy and prophylaxis to treat or prevent bleedings is very demanding owing to the short half-life (HL) of factor concentrates (no more than 12-14 h for FVIII or 16-18 h for FIX). Patients are very eager to prolong the intervals between bolus. The enhanced HL of long-acting recombinant FIX (rFIX) concentrates seems to fulfill this expectance. Areas covered: Great improvements have been achieved in the bio-engineering of new rFIX concentrates. Production, formulation, pharmacokinetics, pharmacodynamics, efficacy and tolerability of albutrepenonacog alfa (rIX-FP, trade name Idelvion) will be addressed. rIX-FP is produced by expression of genetically linked FIX and albumin in Chinese Hamster Ovary cells. rIX-FP exhibits a long HL, low clearance and small volume of distribution. Expert opinion: There is no doubt that rIX-FP, as well as other long-acting rFIX concentrates, will facilitate and improve the adherence to therapy of younger hemophilia patients, toddlers and children. Efficacy, safety and immunogenicity of rIX-FP must be assessed not only during the regulatory clinical trials but also by post-marketing surveillance. PMID- 27677191 TI - 24-hour outpatient ECG as a screening method in patients with primary hyperparathyroidism. AB - PURPOSE: Patients with primary hyperparathyroidism are characterized by increased calcium plasma concentrations, which in turn could have a potential to induce ECG changes, especially shortening of the QT interval. Therefore, the aim of this study was to evaluate, whether the routine 24-hours outpatient ECG monitoring could be used for screening the primary hyperparathyroidism. METHODS: Totally, 31 patients (mean age, 59.2 +/- 12.99 years) with primary hyperparathyroidism were compared to 20 healthy controls. All patients underwent mineral metabolism biochemical evaluation, ultrasound or scintigraphy of the neck, and a 24-hour outpatient ECG. The device detected QT, QTc, and RR intervals during a 24-hour period. RESULTS: Significantly higher calcium concentrations were confirmed in patients when compared to controls (2.38 +/- 0.12 vs 2.92 +/- 0.29 mmol/l; p < 0.001). However, no significant differences were found between controls and patients in QT interval and overall heart rate. CONCLUSION: Although shortening of the QT interval is a common ECG finding in patients with hyperparathyroidism, it seems that 24-hour outpatient ECG is not suitable for primary hyperparathyroidism screening (Tab. 2, Fig. 4, Ref. 28). PMID- 27677192 TI - Does seasonality of births in diabetes mellitus reflect pathogenetic differences? AB - OBJECTIVES: This study indicates that the seasonality of births of patients with DM1 and DM2 has occurred in their adolescence or adulthood. BACKGROUND: Patients with Diabetes mellitus type 2 (DM2) with the maturity onset have different seasonal birth patterns from those with Diabetes mellitus type 1 (DM1) with the maturity onset, or DM1children. METHODS: Monthly numbers of births of 81 and 236 children with DM1 and DM2, respectively, in adolescent or adult age, were adapted to different actual length of calendar months. The 12- and 6-month rhythm was tested using the cosinor regression with 95% confidence interval versus the hypothesis of null seasonality. RESULTS: Regarding DM1 with maturity onset, annual and semiannual rhythm was significant in both genders, with the increase in birth numbers from November to January and decrease in March, April and August. In DM2, only female data displayed a significant annual rhythm, with an increase in birth from April to August and decrease from October to December. CONCLUSION: The birth seasonality related to DM1 in adolescent or adult age appears to be reciprocal, compared to DM1 in childhood. For DM2, the seasonality of births was found only in females. The increase in female fecundity seems to be related to an increase in the risk of DM2 in female offspring. The outcomes could help in identifying environmental and endogenous factors related to seasonality cycle (Tab. 1, Fig. 1, Ref. 18). PMID- 27677193 TI - Effectiveness of breast electrical impedance imaging for clinically suspicious breast lesions. AB - OBJECTIVES AND BACKGROUND: This study was designed to compare the usefulness of the breast electrical conductivity measures performed in a surgical examination room against conventional breast screening modalities for identifying the symptomatic lesions of the breast tissue. METHODS: A group of 181 patients were examined with Ultrasonography (USG), Mammography (MG), Electrical Impedance Scanning (EIS) modalities and were followed-up 24 months to clarify in terms of the lesion tumour progression relationship. Tumour biopsy was determined as an endpoint of the study. RESULTS: According to USG, 13 (7.2 %) lesion were suspicious, where as EIS was reported 22 (12.2 %). 2 of these 9 patients were presented as BI-RADS 4 and histopathologic result was proven as malignant disease during 6 months short-interval follow-up. EIS exhibited compatible sensitivity (81.2 %), accuracy (84.6 %) and PPV (81.8 %) rates with USG in BI-RADS 4 subgroup, combination of these modalities raised sensitivity rates to 92.31 %, accuracy and PPV to 100 %. EIS results in BI-RADS 3 subgroup were pointed out 77.8 % specificity and 87.5 % NPV rates. CONCLUSION: Breast electrical impedance measures should be useful to reduce the number of the unnecessary follow-up and biopsy rates in the clinical setting (Tab. 2, Fig. 2, Ref. 39). PMID- 27677194 TI - The effect of prostaglandin induced labor and selected factors on the occurrence and extent of birth-canal injuries. AB - OBJECTIVES: To determine the effect of labor induction using prostaglandin, gestation period and delivery type on the cause and extent of birth-canal injuries. METHODS: A retrospective study based on the records of II. GPK UNB Ruzinov. The total set (n = 1377) consisted of patients who went into labor in second half of the year 2014 at this clinic. The research used categorical data divided into groups of factors (induction, week of delivery, type of delivery) and birth injuries. Using the chi-square test and Fisher's test we evaluated individual statistical dependences. The results with the highest level of significance are expressed through contingency tests (Phi coefficient, contingency coefficient, Cramer's V). Finally, because of the highest level of significance we have done a cohort study to express the incidence of relationship between non-operative delivery per vaginam and 1st degree ruptura perieni. RESULTS: Labor induction with prostaglandins has a positive impact on the cause and extent of birth-canal injuries, namely the increased risk of vaginal walls tearing and uterine ruptures. We confirmed that the induction of labor using PG carries a demonstrable risk of pregnancy termination by cesarean section (p = 6.17x10-9). Birth-canal injuries are also affected by the type of delivery. Non operative vaginal delivery is a significant risk factor for first-degree perineal tear (RR = 25.52 95% CI 10.58, 61.60, OR = 33.06 95% CI 13.51, 80.90). Significant risk factors for third-grade perineal tear during vaginal delivery are forceps (p = 0.005534) / vacuum extractor (p = 0.03554). CONCLUSION: In a group of 1377 patients we have demonstrated that the labor induction with prostaglandins, gestation period and type of delivery significantly influence the occurrence and extent of birth-canal injuries (Tab. 3, Ref. 9). PMID- 27677195 TI - Recidivous cholesteatoma: DWI MR after canal wall up and canal wall down mastoidectomy. AB - OBJECTIVES: To investigate the correlation between preoperative non-echo planar diffusion-weighted (non-EPI DWI) MR imaging with surgical findings of recidivous middle ear cholesteatoma after canal wall up (CWU) and canal wall down (CWD) mastoidectomy. BACKGROUND: The detection of recidive cholesteatoma after CWU and after CWD procedures, when the trepanation cavity is spontaneously closed by soft tissue, is possible by second-look and revision surgery. However, many cases prove to be negative of the disease. To avoid unnecessary operational risks we adopted a novel imaging method to evaluate its potential in the detection of recidivous cholesteatoma. MATERIAL AND METHODS: The prospective study included 27 cases. Fifteen cases were revised after CWD and 12 cases were second-look surgeries after CWU procedures. All patients underwent the MR protocol: T2 weighted, T1-weighted and non-EPI DWI. The finding on MR correlated with peroperative presence of cholesteatoma. RESULTS: Non-EPI DWI sequence showed an increased signal intensity in 16/27 (59 %) cases. This correlated with surgical findings in all 7 patients after CWU and in 8 patients after CWD. The overall sensitivity, specificity, positive and negative predictive values of non-EPI DWI were 83.3 %, 88.8 %, 93.8 % and 72.7 %, respectively. DWI presented a sensitivity of 100 % and specificity of 85.7 % in the subgroup of patients after CWD mastoidectomy. CONCLUSION: Residual and/or recurrent cholesteatoma can be accurately detected by DWI MR. It can be used as a screening method to select patients, who are indicated to second-look or revision surgery after CWU and CWD mastoidectomy (Tab. 1, Fig. 3, Ref. 49). PMID- 27677196 TI - Prevalence of Helicobacter pylori infection and its association with lipid profiles. AB - OBJECTIVE: To evaluate the prevalence of Helicobacter pylori (H. pylori, HP) infection in subjects receiving routine physical examination and its associations with age, sex, body mass index (BMI) and lipid profiles. MATERIALS AND METHODS: Clinical information of 22,103 individuals who took routine physical examinations, including that on age, gender, height, weight, triglyceride, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and data of HP infection were collected and analyzed. RESULTS: H. pylori infection rate in 22,103 subjects taking routine physical examination was 44.5 %. More men tended to be infected with H. pylori than women (45.9 % vs 42.8 %; p < 0.01). The highest positive rate group was in the age group of 30-39 years (46.8 %) and the lowest rate was in the age group younger than 30 years (40.5 %). The obese had higher infection rate than the non-obese (p < 0.01). Mann Whitney U test was used to explore the relationships between lipid profiles and H. pylori infection. There were significant associations among HDL, triglyceride and HP infection (p < 0.01). However, significant differences were not confirmed between cholesterol, LDL and H. pylori infection. CONCLUSION: H. pylori infection was common among subjects receiving physical examination in Shanghai and it was most significantly associated with HDL and triglyceride, indicating that H. pylori might be a new cardiovascular risk factor (Tab. 3, Ref. 23). PMID- 27677197 TI - Can platelet-rich plasma be used safely in intra-abdominal operations? AB - OBJECTIVES: In this study, it was aimed to investigate whether or not platelet rich plasma (PRP) causes intra-abdominal adhesions and therefore, whether or not PRP can be used safely in intra-abdominal operations. METHODS: Of the total of 35 animals, 5 were used as donors for the preparation of platelet-rich plasma (PRP). The surgical procedures were performed on the remaining 30 animals. These rats were randomized and divided into 3 groups of 10. In Group 1, no adhesion induction was performed. Adhesion was induced by cecal abrasion and peritoneal resection model in Groups II and IIII. In Group 2, no treatment was given. In Group 3, 1 cc PRP was applied on the cecum. The rats were sacrificed on postoperative day 21. RESULTS: According to adhesion scores, the difference between the sham and PRP groups was not statistically significant. There was also no significant difference between the control and PRP groups, but the adhesion scores in the PRP group was lower than those in the control group. On histopathological evaluation, the difference between the sham and PRP groups was not statistically significant. There was also no significant difference between the control and PRP groups, but the average fibrosis and inflammation scores in the PRP group were lower than those in the control group. CONCLUSION: The results of the present study have demonstrated that PRP neither reduced nor exacerbated postoperative adhesions. Thus, PRP can be used safely in experimental and clinical studies where it will be applied intra-abdominally (Tab. 2, Fig. 3, Ref. 11). PMID- 27677198 TI - Effects of beta-glucan on protection of young and aged rats from renal ischemia and reperfusion injury. AB - BACKGROUND: Ischemia-reperfusion injury is one of the leading causes of acute renal failure which is a common clinical event leading to development of chronic kidney disease and a high mortality; especially in elderly people. beta-glucans are glucose polymer groups with free-radical scavenger, macrophage activator, and immune defense inducer functions. We designed this study to determine the possible protective effects of beta-glucan against renal ischemia-reperfusion injury comparatively in young and aged rats. METHODS: Rats were assigned to the following groups: Young and aged sham, young and aged ischemia-reperfusion, young and aged beta-glucan, young and aged ischemia-reperfusion+beta-glucan. At the end of the experiment, following collection of blood samples, rats were sacrificed and kidneys were removed for histopathological and biochemical examination. RESULTS: Mean tissue histopathological damage scores of young beta-glucan group was lower than that of young ischemia-reperfusion group, and of aged beta-glucan group was lower than that of aged ischemia-reperfusion group. Urea and creatinine levels of young and aged of sham group and beta-glucan administered groups were all lower than those of ischemia-reperfusion and beta-glucan+ischemia-reperfusion groups. Oxidative stress indexes of ischemia-reperfusion groups were increased however ; oxidative stress indexes of beta-glucan administered to young and aged rats were lower than those of ischemia-reperfusion groups. CONCLUSIONS: We conclude that beta-glucan is effective to protect kidneys from ischemia reperfusion-induced oxidative damage, especially in young rats (Fig. 6, Ref. 45). PMID- 27677199 TI - Dexmedetomidine protected COPD-induced lung injury by regulating miRNA-146a. AB - OBJECTIVE: To study the mechanism of protection provided by dexmedetomidine against COPD-induced lung injury. METHODS: COPD rat model was determined by measuring lung function, and comparing HE staining between two different groups. We got the lung tissue and cells from the control and COPD groups. The cells were divided into three groups: control group, and blank and drug groups that were from the COPD rats. Cell apoptosis, relative gene expression and TNF-alpha and IL 1beta from nutrient solution were measured. RESULTS: The TV, PEF, EF50, FEV0.3 and FEV0.3/FVC in COPD group were significantly lower than in control group (1.26+/-0.17 vs 2.65+/-0.21; 17.61+/-0.35 vs 38.55+/-0.24; 1.20+/-0.14 vs 1.81+/ 0.06; 2.52+/-0.28 vs 4.44+/-0.26; 63.39+/-0.22 vs 88.45+/-0.34, p < 0.05, respectively). Cell apoptosis was significantly different in blank and drug groups (21.65+/-0.86 vs 10.74+/-0.15; p < 0.05, respectively). The gene expressions of miRNA-146a, p53 and Bcl-2 were significantly downregulated compared with blank group. CONCLUSION: Dexmedetomidine protected COPD-induced lung injury by inhibiting miRNA-146a expression to reduce cell apoptosis (Tab. 1, Fig. 3, Ref. 25). PMID- 27677200 TI - Phenytoin accelerates tendon healing in a rat model of Achilles tendon rupture. AB - INTRODUCTION: Tendons are vulnerable to various types of acute or chronic injures. Different methods have been investigated to achieve better healing. Phenytoin is a drug which could stimulate fibroblasts to produce collagen. This experimental study was performed to assess the effect of phenytoin on tendon healing in a rat model of tendon rupture. METHODS: Thirty healthy rats were divided into 3 groups, 1) Sham group; 2) Tendon rupture; 3) Tendon rupture+phenytoin (100 mg/kg intraperitoneally) for 21 days. On 21st day after tendon injury, the rats were anesthetized and tendon tissue was sampled for studying by light and electron microscopy. RESULTS: Qualitative and quantitative microscopic comparisons of the repair tissues of both groups were made on the 21st day. The results obtained from light and electron microscopy studies showed that tendon tissue healing was significantly better in phenytoin group compared to the control group (p < 0.05). CONCLUSIONS: Systemic administration of phenytoin may have a positive effect on tendon healing by increasing fibroblast quantity, fibrillar collagen synthesis, vascularity, and suppressing inflammation (Tab. 2, Ref. 25). PMID- 27677201 TI - Body proportions as possible predictors for free gracilis one-stage facial reanimation. AB - BACKGROUND: Gracilis muscle and its motor nerve belongs to most commonly used flap for facial reanimation. However, it is performed in two steps, which is time consuming. One stage technique can be also performed, but the length of the motor nerve cannot be currently determined before surgery. AIM: The present study was conducted in order to evaluate the body composition on the length and suitability of the motor nerve of gracilis muscle for one stage facial reanimation. METHODS: The gracilis flaps along with the motoric nerve were dissected from 20 fresh cadavers (6 females, 14 males). The length of the lower extremity from superior iliac anterior spine to the bottom of the heel and BMI were measured. Regression analysis of lower extremity length and BMI to the actual length of the motor nerve of gracilis flap was performed. RESULTS: The linear regression analysis showed a positive correlation between the length of the lower limb and the size of the motor nerve length (r = 0.5060, p < 0.05), as well as between the BMI and the size of the motor nerve length (r = 0.5073, p < 0.05). Also, the males had longer motor nerve when compared to females by 13 % (p < 0.05). No difference between females and males in BMI was observed. CONCLUSION: The length from the superior iliac anterior spine, BMI and gender seemed to be potential factors that could help to predict the length of the gracilis flap motor nerve for the one stage facial reanimation. However, further studies evaluating other anatomical factors and validating the possible prediction rule for one stage reanimation success are needed (Fig. 3, Ref. 14). PMID- 27677202 TI - Robust and High-Throughput Method for Anionic Metabolite Profiling: Preventing Polyimide Aminolysis and Capillary Breakages under Alkaline Conditions in Capillary Electrophoresis-Mass Spectrometry. AB - Capillary electrophoresis-mass spectrometry (CE-MS) represents a high efficiency microscale separation platform for untargeted profiling of polar/ionic metabolites that is ideal for volume-restricted biological specimens with minimal sample workup. Despite these advantages, the long-term stability of CE-MS remains a major obstacle hampering its widespread application in metabolomics notably for routine analysis of anionic metabolites under negative ion mode conditions. Herein, we report for the first time that commonly used ammonia containing buffers compatible with electrospray ionization (ESI)-MS can compromise the integrity of fused-silica capillaries via aminolysis of their outer polyimide coating. Unlike organic solvent swelling effects, this chemical process occurs under aqueous conditions that is dependent on ammonia concentration, buffer pH, and exposure time resulting in a higher incidence of capillary fractures and current errors during extended operation. Prevention of polyimide aminolysis is achieved by using weakly alkaline ammonia containing buffers (pH < 9) in order to preserve the tensile strength of the polyimide coated fused-silica capillary. Alternatively, less nucleophilic primary/secondary amines can be used as electrolytes without polyimide degradation, whereas chemically resistant polytetrafluoroethylene coating materials offer higher pH tolerance in ammonia. In this work, multisegment injection (MSI)-CE-MS was used as multiplexed separation platform for high throughput profiling of anionic metabolites when using optimized buffer conditions to prevent polyimide degradation. A diverse range of acidic metabolites in human urine were reliably measured by MSI-CE-MS via serial injection of seven urine samples within a single run, including organic acids, food-specific markers, microbial-derived compounds and over-the counter drugs as their sulfate and glucuronide conjugates. This approach offers excellent throughput (<5 min/sample) and acceptable intermediate precision (average CV ~ 16%) with high separation efficiency as reflected analysis of 30 anionic metabolites following 238 repeated sample injections of human urine over 3 days while using a single nonisotope internal standard for data normalization. Careful optimization and rigorous validation of CE-MS protocols are crucial for developing a rapid, low cost, and robust screening platform for metabolomics that is amenable to large-scale clinical and epidemiological studies. PMID- 27677203 TI - Antioxidant Mechanism of Betaine without Free Radical Scavenging Ability. AB - Betaine (BET) is a native compound widely studied as an antioxidant in agriculture and human health. However, the antioxidant mechanism of BET remains unclear. In this research, radical scavenging assays showed that BET had little free radical scavenging activity. However, the antioxidant activity of BET was confirmed by cellular antioxidant activity (CAA) and erythrocyte hemolysis assays. The results of quantitative PCR (qPCR) and enzyme activity determination kits showed that the antioxidant activity of BET was not due to the gene expression and activity of antioxidases. High-pressure liquid chromatography (HPLC) assessment of the effect of BET on sulfur-containing amino acid metabolism showed that BET increased the levels of nonenzymatic antioxidants,S adenosylmethionine (SAM) and methionine (p < 0.05), via the regulation of the methionine-omocysteine cycle. Additionally, the three methyl groups of BET were found to play a key role in its antioxidant activity. The possible reason was that because of the hydrophobicity of the three methyl groups and hydrophilicity of the carboxyl of BET, a tight protective membrane was formed around cells to prevent oxidative stress inducer from inducing ROS generation and cell damage. In conclusion, the antioxidant mechanism of BET was found to enhance nonenzymatic antioxidant defenses via the methionine-homocysteine cycle and form a protective membrane around cells. PMID- 27677204 TI - Induction of labor in elderly nulliparous women. AB - PURPOSE: Maternal age is an important consideration for antenatal care, labor and delivery. We aimed to evaluate the induction of labor (IoL) failure rates among elderly nulliparous women. MATERIALS AND METHODS: We conducted a retrospective analysis of all nulliparous women at 34 + 0 to 41 + 6 weeks, undergoing cervical ripening by prostaglandin E2 (PGE2) vaginal insert. Study group included elderly (>=35 years) nulliparous and control group included non-elderly (<35 years) nulliparous women. Primary outcome was IoL failure rate and secondary outcome was cesarean delivery rate. Outcomes were compared between the groups by univariate analysis followed by regression analysis to adjust results to potential confounders. RESULTS: Of 537 women undergoing IoL, 69 (12.8%) were elderly. The univariate analysis demonstrated no difference in IoL failure rate (26.5% versus 34.8%, p = 0.502) between groups. However, elderly nulliparous women had higher rates of cesarean delivery (36.2% versus 21.4%, p = 0.009). This difference was no longer significant after adjustment for maternal body mass index, indication for delivery, birth weight and gestational age at delivery. CONCLUSION: Among nulliparous women, older maternal age is not associated with higher rates of IoL failure or cesarean deliveries. PMID- 27677206 TI - Erratum. PMID- 27677205 TI - Teaching population health: using the classroom as a bridge to the community. PMID- 27677207 TI - Association of intimate partner violence with sociodemographic factors in married women: a population-based study in Iran. AB - Intimate partner violence (IPV) is a neglected public health issue in Iran. This study was conducted among married women residing in urban Rasht (northern Iran), to estimate the prevalence and frequency of different forms of IPV from husband and their associations with socio-demographic factors. We carried out a population-based cross-sectional survey with cluster sampling design from February to October 2015. The samples consisted of married women aged >= 18 years with total household in Rasht city (north Iran) as the sample frame. We administered the Revised Conflict Tactics Scale (CTS-2) to estimate prevalence of past-year IPV. Of 2091 women, 57.1% had suffered psychological aggression, 27.6% physical abuse, 26.6% sexual abuse, and 6.9% injury. A significant association with IPV was found for women with, age <= 40 years, unemployed, low education, husband's addiction and rented-householders. Women who experienced physical abuse, had less age at marriage than women without violence. Also women with sexual coercion had less length of marriage than other non-abused women. On logistic regression, the strongest predictor of psychological, physical and sexual abuse was unemployment of spouse, whereas for injury it was low educational level (<12 years) of women. Our findings suggest that risk of IPV is high in our population. There is an obvious need of preventive and treatment activities. Our findings point at that various forms of abuse are different from each other in terms of differing characteristics of the perpetrators and it might be that also different strategies are needed to reduce and prevent these violence. Confirmation by further research is needed. PMID- 27677208 TI - Preselection test of jury for improvement of olfactometric certification efficiency. AB - To certificate an olfactometric jury, laboratories usually follow up the panelist screening methodology described in the European Standard EN 13725/2003. The procedure takes a lot of time, labour and money. In laboratory routine of LCQAr - Laboratory of Air Quality Control, of Federal University of Santa Catarina, Brazil, it was found that the efficiency of jury approvals used to be as low as around 30%. In order to improve the efficiency, a quick preselection test was proposed and tried for late certification recommended by EN 13725. The methodology to create the preselection test was based on the conceptions of the standards EN 13725 (CEN, 2003), ASTM 679 (2011) and ASTM 544 (2010). In the trial test, 31 volunteers participated and then screened according to the EN13725 standard. It was verified that the efficiency increased to 46% from about 30% after the introduction of the preselection test. The experiments were conducted at LCQAr, with the contribution of Water Research Centre of University of New South Wales, Australia. PMID- 27677210 TI - Rapidly progressive infiltrated plaques in a transplant recipient. PMID- 27677209 TI - Mechanical antihypersensitivity effect induced by repeated spinal administrations of a TRPA1 antagonist or a gap junction decoupler in peripheral neuropathy. AB - Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by d-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). Experiments were performed in rats with spared nerve injury (SNI) and chronic intrathecal catheter. Drugs were administered twice daily for the first seven injury days or only once seven days after injury. Mechanical hypersensitivity was assessed with monofilaments. Acute and prolonged treatment with Chembridge-5861528 (a TRPA1 antagonist), carbenoxolone (an inhibitor of activated astrocytes), or gabapentin (a comparison drug) attenuated tactile allodynia-like responses evoked by low (2g) stimulus. However, antihypersensitivity effect of these compounds was short of significance at a high (15g) stimulus intensity. No preemptive effects were observed. In healthy controls, carbenoxolone failed to prevent hypersensitivity induced by spinal cinnamaldehyde, a TRPA1 agonist. TRPA1 and DAAO mRNA in the DRG but not SDH were slightly increased in SNI, independent of drug treatment. The results indicate that prolonged peri-injury block of spinal TRPA1 or inhibition of spinal astrocyte activation attenuates maintenance but not development of mechanical (tactile allodynia-like) hypersensitivity after nerve injury. PMID- 27677211 TI - Targeted deletion of the Kv6.4 subunit causes male sterility due to disturbed spermiogenesis. AB - Electrically silent voltage-gated potassium (KvS) channel subunits (i.e. Kv5-Kv6 and Kv8-Kv9) do not form functional homotetrameric Kv channels, but co-assemble with Kv2 subunits, generating functional heterotetrameric Kv2--KvS channel complexes in which the KvS subunits modulate the Kv2 channel properties. Several KvS subunits are expressed in testis tissue but knowledge about their contribution to testis physiology is lacking. Here, we report that the targeted deletion of Kv6.4 in a transgenic mouse model (Kcng4-/-) causes male sterility as offspring from homozygous females were only obtained after mating with wild-type (WT) or heterozygous males. Semen quality analysis revealed that the sterility of the homozygous males was caused by a severe reduction in total sperm-cell count and the absence of motile spermatozoa in the semen. Furthermore, spermatozoa of homozygous mice showed an abnormal morphology characterised by a smaller head and a shorter tail compared with WT spermatozoa. Comparison of WT and Kcng4-/- testicular tissue indicated that this inability to produce (normal) spermatozoa was due to disturbed spermiogenesis. These results suggest that Kv6.4 subunits are involved in the regulation of the late stages of spermatogenesis, which makes them a potentially interesting pharmacological target for the development of non hormonal male contraceptives. PMID- 27677212 TI - Effects of flavonol glycosides on liposome stability during freezing and drying. AB - Flavonoids are a large and diverse group of plant secondary metabolites that are mainly present as glycosides. They are often accumulated in response to abiotic stresses such as UV radiation, drought, cold and freezing. The most extensively studied function of flavonoids is their antioxidant activity although their importance as antioxidants in plants has been questioned. We therefore aim to study effects of flavonols on cellular stress tolerance that are independent of their antioxidant function. Here we investigate the effects of the glycosylated flavonols kaempferol-3-O-glucoside, kaempferol-7-O-glucoside, quercetin-3-O glucoside and quercetin-3-O-rhamnoside on liposome stability after freezing and drying. Insertion of flavonols in lipid bilayers destabilized egg phosphatidylcholine (EPC) liposomes and to a lesser extent vesicles made from equal proportions of EPC and egg phosphatidylethanolamine (EPE) during a freeze thaw cycle, while liposomes containing the unsaturated non-bilayer lipid 18:2 PE were either unaffected or slightly stabilized. In general, the kaempferol derivatives were more destabilizing for liposomes during freezing than the quercetin derivatives. Fourier-transform infrared spectroscopy revealed that all flavonols were localized in the interfacial region of the lipid bilayers, forming H-bonds with the lipid phosphate and carbonyl groups. The phase transition temperature of dry 16:0/18:1 PC (POPC) and POPC/EPE liposomes was decreased by 75 degrees C and 55 degrees C, respectively. Changes in the vibration bands attributed to the phenolic ring structures of the flavonols in the presence of liposomes provided further evidence of interactions of these molecules in particular with the interfacial region of the bilayers. PMID- 27677213 TI - Effect of dental technician disparities on the 3-dimensional accuracy of definitive casts. AB - STATEMENT OF PROBLEM: Studies that evaluated the effect of dental technician disparities on the accuracy of presectioned and postsectioned definitive casts are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the accuracy of presectioned and postsectioned definitive casts fabricated by different dental technicians by using a 3-dimensional computer-aided measurement method. MATERIAL AND METHODS: An arch-shaped metal master model consisting of 5 abutments resembling prepared mandibular incisors, canines, and first molars and with a 6-degree total angle of convergence was designed and fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM) technology. Complete arch impressions were made (N=110) from the master model, using polyvinyl siloxane (PVS) and delivered to 11 dental technicians. Each technician fabricated 10 definitive casts with dental stone, and the obtained casts were numbered. All casts were sectioned, and removable dies were obtained. The master model and the presectioned and postsectioned definitive casts were digitized with an extraoral scanner, and the virtual master model and virtual presectioned and postsectioned definitive casts were obtained. All definitive casts were compared with the master model by using computer-aided measurements, and the 3-dimensional accuracy of the definitive casts was determined with best fit alignment and represented in color-coded maps. Differences were analyzed using univariate analyses of variance, and the Tukey honest significant differences post hoc tests were used for multiple comparisons (alpha=.05). RESULTS: The accuracy of presectioned and postsectioned definitive casts was significantly affected by dental technician disparities (P<.001). The largest dimensional changes were detected in the anterior abutments of both of the definitive casts. The changes mostly occurred in the mesiodistal dimension (P<.001). CONCLUSIONS: Within the limitations of this in vitro study, the accuracy of presectioned and postsectioned definitive casts is susceptible to dental technician differences. PMID- 27677215 TI - Retentive strength of implant-supported CAD-CAM lithium disilicate crowns on zirconia custom abutments using 6 different cements. AB - STATEMENT OF PROBLEM: The optimal retention of implant-supported ceramic crowns on zirconia abutments is a goal of prosthodontic treatment. PURPOSE: The purpose of this in vitro study was to evaluate the retentive strength of implant supported IPS e.max CAD-CAM (e.max) crowns bonded to custom zirconia implant abutments with different cements. MATERIAL AND METHODS: An optical scan of a zirconia custom abutment and a complete-coverage modified crown was designed using an intraoral E4D scanner. One hundred twenty lithium disilicate crowns (IPS e.max CAD) were cemented to 120 zirconia abutment replicas with 1 of 6 cements: Panavia 21 (P21), Multilink Hybrid Abutment (MHA), RelyX Unicem 2 (RXU), RelyX Luting Plus (RLP), Ketac Cem (KC), and Premier Implant (PI). The specimens were stored at 37 degrees C in 100% humidity for 24 hours. Half of the specimens were thermocycled for 500 cycles. The retentive force was measured using a pull-out test with a universal testing machine. Mean retentive strengths (MRS) were calculated using 2-way ANOVA and the Tukey-Kramer test (alpha=.05). RESULTS: The MRS (MPa) after 24-hour storage were P21 (3.1), MHA (2.5), RXU (2.5), RLP (1.3), KC (0.9), and PI (0.5). The MRS after thermocycling were MHA (2.5), P21 (2.2), RLP (1.8), KC (1.4), RXU (1.1), and PI (0.3). P21 had the highest MRS after 24 hour storage (P<.001), but after thermocycling MHA had the highest MRS (P<.001). RXU showed a significant decrease in MRS after thermocycling (P<.05). Cement residue was mostly retained on the zirconia abutments for P21, while for the other cements' residue was retained on the lithium disilicate crowns. CONCLUSIONS: The cements tested presented a range of retentive strengths, providing the clinician with a choice of more or less retentive cements. MHA was the most retentive cement after thermocycling. Thermocycling significantly affected the retentive strengths of the P21 and RXU cements. PMID- 27677214 TI - Marginal and internal fit of CAD-CAM-fabricated composite resin and ceramic crowns scanned by 2 intraoral cameras. AB - STATEMENT OF PROBLEM: The precision of fit of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by digital impression and restorative material. PURPOSE: The purpose of this in vitro study was to evaluate by microcomputed tomography (MUCT) the marginal and internal adaptation of composite resin and ceramic complete crowns fabricated with 2 different intraoral cameras and 2 restorative materials. MATERIAL AND METHODS: Ten extracted human third molars received crown preparations. For each prepared molar, 2 digital impressions were made with different intraoral cameras of the CEREC system, Bluecam and Omnicam. Four groups were formed: LB (Lava Ultimate+Bluecam), EB (Emax+Bluecam), LO (Lava Ultimate+Omnicam), and EO (Emax+Omnicam). Before measuring the precision of fit, all crowns were stabilized with a silicone material. Each unit (crown + prepared tooth) was imaged with MUCT, and marginal and internal discrepancies were analyzed. For the 2D analysis, 120 measurements were made of each crown for marginal adaptation, 20 for marginal discrepancy (MD), and 20 for absolute marginal discrepancy (AMD); and for internal adaptation, 40 for axial space (AS) and 40 for occlusal space (OS). After reconstructing the 3D images, the average internal space (AIS) was calculated by dividing the total volume of the internal space by the contact surface. Data were analyzed with 2-way ANOVA and quantile regression. RESULTS: Regarding marginal adaptation, no significant differences were observed among groups. For internal adaptation measured in the 2D evaluation, a significant difference was observed between LO and EO for the AS variable (Mann-Whitney test; P<.008). In assessment of AIS by the 3D reconstruction, LB presented significantly lower values than the other groups (Tukey post hoc test; P<.05). Bluecam presented lower values of AIS than Omnicam, and composite resin crowns showed less discrepancy than did ceramic crowns. CONCLUSIONS: The marginal adaptations assessed in all groups showed values within the clinically accepted range. Moreover, the composite resin blocks associated with the Bluecam intraoral camera demonstrated the best results for AIS compared with those of the other groups. PMID- 27677216 TI - A two-step functional impression technique for the fabrication of an implant retained silicone auricular prosthesis. AB - Excessive movement of the underlying tissue bed can lead to poor retention of an implant-retained silicone auricular prosthesis. This article describes a 2-step impression technique with a secondary functional pickup impression of the wax pattern. A wide range of tissue movements can be recorded while maintaining a stable relationship between the abutment analog assembly and retentive elements. The definitive cast is modified accordingly to provide an accurate reproduction of the patient's tissues during function, thus, increasing the overall retention and stability of the definitive prosthesis. PMID- 27677217 TI - Influence of implant number on the movement of mandibular implant overdentures. AB - STATEMENT OF PROBLEM: The rotational movement of an implant overdenture (IOD) has a negative effect on the perceived masticatory ability of the denture wearer. However, the influence of implant number on the movement of IODs has not been investigated. PURPOSE: The purpose of this in vitro study was to evaluate the denture movement of mandibular IODs anchored by different numbers of implants. MATERIAL AND METHODS: An edentulous mandibular test model with artificial mucosa and 5 experimental overdentures (N=5) was fabricated. The locator attachment system with blue nylon inserts was chosen for this study. Three implant positions were prepared: anterior midline (1-IOD), bilateral lateral incisor regions (2 IOD), and anterior midline and bilateral canine regions (3-IOD). Vertical loads of 50 N were applied to the mid-anterior region, the left canine region, the left premolar region, and the left first molar region. The vertical and horizontal displacements at the right distal edge and the vertical displacements at the loading point were measured. The displacement values were statistically analyzed using a 1-way analysis of variance and the post hoc Tukey honest significant difference test with the implant number as a factor. In addition, the values of the vertical and horizontal displacements at the distal edge of the overdenture were statistically compared using a paired t test, and the values of the vertical displacement at the distal edge of the overdenture were statistically analyzed by a repeated measures analysis of variance and the post hoc Tukey honest significance difference test with the loading point as a factor (a=.05). RESULTS: Upon anterior loading, the 2-IOD showed significantly larger vertical displacements at the right distal edge than the 1-IOD or 3-IOD (P<.01). The horizontal displacements at the right distal edge were small compared with the vertical displacements at the same point, although the displacement of the 2-IOD was significantly larger than that of the 1-IOD upon anterior loading (P=.03). The magnitude of the vertical displacement at the loading point of the 2-IOD was significantly larger than that of the 3-IOD upon anterior loading (P<.01). No statistically significant differences were shown under the other conditions for each loading (P>.05). CONCLUSIONS: Within the limitations of this in vitro study, the following conclusions were drawn: During mastication with the anterior teeth, the use of 2 implants for anchoring an IOD increased the rotation of the denture base more than the use of 1 or 3 implants. The horizontal movements of the IODs were small compared with the vertical movements. Denture movement under the occlusal force in the molar region was smaller than that in the anterior region. PMID- 27677218 TI - Practice-based preclinical instruction for gingival displacement with animal models. AB - STATEMENT OF PROBLEM: Gingival displacement is recognized as a substantive and difficult procedure in fixed prosthodontics. However, a realistic simulation of gingival displacement is unavailable for preclinical dental students. PURPOSE: The purpose of this study was to evaluate whether practice-based preclinical instruction of gingival displacement with animal models could improve students' skill in patient care. MATERIAL AND METHODS: Isolated bovine mandibles (calves were younger than 6 months of age) and isolated porcine hemimandibles were prepared for this study. Twenty-two general dental practitioners with at least 5 years of experience were randomly selected and assigned to perform gingival displacement on both bovine and porcine jaws. Those practitioners were then asked to assess the clinical similarity of gingival displacement between human teeth and animal teeth. The data were analyzed with the paired t test (alpha=.05). Upon confirmation that the animal jaw provided a similar gingival displacement environment to that of human teeth, 80 predoctoral dental students were enrolled and randomized into 2 groups. Half of them underwent the new practice-based instruction, while the others underwent traditional preclinical teaching only (lectures, online video, or live demonstration). After preclinical learning, clinical performance in gingival displacement was evaluated for all students in terms of the effect of gingival displacement and quality of impression. The data were analyzed with the chi-square test (alpha=.05). RESULTS: The dentogingival environments of porcine and bovine jaws were similar to those of human jaws, and no significant difference was detected between these 2 animal models (P=.178). A significant increase occurred in the acceptable rate of the effect of gingival displacement (P<.001) and the quality of impression (P<.001) among students who received the practice-based instruction compared with those who received traditional teaching. CONCLUSIONS: These findings suggest that this practice based instruction of gingival displacement with animal models is an effective method of promoting dental students' learning of gingival displacement. PMID- 27677219 TI - A microcomputed tomography evaluation of the marginal fit of cobalt-chromium alloy copings fabricated by new manufacturing techniques and alloy systems. AB - STATEMENT OF PROBLEM: Although new digital manufacturing techniques are attracting interest in dentistry, few studies have comprehensively investigated the marginal fit of fixed dental prostheses fabricated with such techniques. PURPOSE: The purpose of this in vitro microcomputed tomography (MUCT) study was to evaluate the marginal fit of cobalt-chromium (Co-Cr) alloy copings fabricated by casting and 3 different computer-aided design and computer-aided manufacturing (CAD-CAM)-based processing techniques and alloy systems. MATERIAL AND METHODS: Single Co-Cr metal crowns were fabricated using 4 different manufacturing techniques: casting (control), milling, selective laser melting, and milling/sintering. Two different commercial alloy systems were used for each fabrication technique (a total of 8 groups; n=10 for each group). The marginal discrepancy and absolute marginal discrepancy of the crowns were determined with MUCT. For each specimen, the values were determined from 4 different regions (sagittal buccal, sagittal lingual, coronal mesial, and coronal distal) by using imaging software and recorded as the average of the 4 readings. For each parameter, the results were statistically compared with 2-way analysis of variance and appropriate post hoc analysis (using Tukey or Student t test) (alpha=.05). RESULTS: The milling and selective laser melting groups showed significantly larger marginal discrepancies than the control groups (70.4 +/-12.0 and 65.3 +/-10.1 MUm, respectively; P<.001), whereas the milling/sintering groups exhibited significantly smaller values than the controls (P=.004). The milling groups showed significantly larger absolute marginal discrepancy than the control groups (137.4 +/-29.0 and 139.2 +/-18.9 MUm, respectively; P<.05). In the selective laser melting and milling/sintering groups, the absolute marginal discrepancy values were material-specific (P<.05). Nonetheless, the milling/sintering groups yielded statistically comparable (P=.935) or smaller (P<.001) absolute marginal discrepancies to the control groups. CONCLUSIONS: The findings of this in vitro MUCT study showed that the marginal fit values of the Co-Cr alloy greatly depended on the fabrication methods and, occasionally, the alloy systems. Fixed dental prostheses produced by using the milling/sintering technique can be considered clinically acceptable in terms of marginal fit. PMID- 27677220 TI - Randomized controlled within-subject evaluation of digital and conventional workflows for the fabrication of lithium disilicate single crowns. Part III: marginal and internal fit. AB - STATEMENT OF PROBLEM: Trials comparing the overall performance of digital with that of conventional workflows in restorative dentistry are needed. PURPOSE: The purpose of the third part of a series of investigations was to test whether the marginal and internal fit of monolithic crowns fabricated with fully digital workflows differed from that of crowns fabricated with the conventional workflow. MATERIAL AND METHODS: In each of 10 participants, 5 monolithic lithium disilicate crowns were fabricated for the same abutment tooth according to a randomly generated sequence. Digital workflows were applied for the fabrication of 4 crowns using the Lava, iTero, Cerec inLab, and Cerec infinident systems. The conventional workflow included a polyvinyl siloxane impression, manual waxing, and heat-press technique. The discrepancy between the crown and the tooth was registered using the replica technique with polyvinyl siloxane material. The dimensions of the marginal discrepancy (Discrepancymarginal) and the internal discrepancy in 4 different regions of interest (Discrepancyshoulder, Discrepancyaxial, Discrepancycusp, and Discrepancyocclusal) were assessed using light microscopy. Post hoc Student t test with Bonferroni correction was applied to detect differences (alpha=.05). RESULTS: Discrepancymarginal was 83.6 +/-51.1 MUm for the Cerec infinident, 90.4 +/-66.1 MUm for the conventional, 94.3 +/-58.3 MUm for the Lava, 127.8 +/-58.3 MUm for the iTero, and 141.5 +/-106.2 MUm for the Cerec inLab workflow. The differences between the treatment modalities were not statistically significant (P>.05). Discrepancyshoulder was 82.2 +/-42.4 MUm for the Cerec infinident, 97.2 +/-63.8 MUm for the conventional, 103.4 +/-52.0 MUm for the Lava, 133.5 +/-73.0 MUm for the iTero, and 140.0 +/-86.6 MUm for the Cerec inLab workflow. Only the differences between the Cerec infinident and the Cerec inLab were statistically significant (P=.036). The conventionally fabricated crowns revealed significantly lower values in Discrepancycusp and Discrepancyocclusal than all the crowns fabricated with digital workflows (P<.05). CONCLUSIONS: In terms of marginal crown fit, no significant differences were found between the conventional and digital workflows for the fabrication of monolithic lithium disilicate crowns. In the occlusal regions, the conventionally manufactured crowns revealed better fit than the digitally fabricated crowns. Chairside milling resulted in less favorable crown fit than centralized milling production. PMID- 27677221 TI - Puerarin exerts the protective effect against chemical induced dysmetabolism in rats. AB - In this study, we aim to explore the potential benefits of puerarin on metabolic function of liver fibrosis (LF) rat induced by carbon tetrachloride (CCl4), and to investigate with the underlying molecular mechanism targeted on liver and pancreas tissues. In methodology, The LF rats were prepared through intragastrically giving CCl4 twice each week (2ml/kg, v/w) for 8weeks, and dosed puerarin (20, 40mg/kg) were given three times each week via intraperitoneal injection. After being conducted with oral glucose tolerance test (OGTT), the blood samples of rat were harvested for biochemical tests, as well as the liver and pancreas were isolated for histological examination and biochemical assays. The findings showed that puerarin-administered rats resulted in reduced glucose tolerance, blood insulin level, sero-enzymes of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and increased plasma level of high-density lipoprotein cholesterol (HDL-C) and reduced low-density lipoprotein cholesterol (LDL-C) content in serum. Further, the intrahepatic collagen deposits were lessened and positive cell of alpha smooth muscle actin (alpha-SMA) was lessened in puerarin treatment, while the pro-apoptotic cell numbers of Caspase 3, Bax in pancreatic islets were reduced dose-dependently. Moreover, the mRNA expressions of toll-like receptor 4 (TLR4) and tumor necrosis factor (TNF-alpha) in liver and pancreas were downregulated. In addition, TNF-alpha protein in the CCl4-lesioned liver and pancreas was reduced. Our findings demonstrate that puerarin contributes to attenuating the metabolic dysfunctions of CCl4-damaged liver and pancreas, in which the possible mechanisms may be linked to inhibition of inflammatory stress and normalization of metabolic homoeostasis in the liver and pancreas. PMID- 27677222 TI - Correlations of PTEN genetic polymorphisms with the risk of depression and depressive symptoms in a Chinese population. AB - OBJECTIVE: This study aimed to investigate the correlations of three common single nucleotide polymorphisms (SNPs) in the PTEN gene (rs701848 T>C, rs2735343 G>C and rs112025902 A>T) with the risk of depression and depressive symptoms in a Chinese population. METHODS: From July 2011 to June 2013, a total of 384 patients with depression and 400 healthy individuals were included in this study. These SNPs in the PTEN gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. The Hamilton Depression Rating Scale (HAMD) was used to evaluate the severity of depression. RESULTS: The C allele of rs701848, the C allele of rs2735343 and the T allele of rs112025902 were associated with an increased risk of depression (odds ratio [OR]=3.814, 95% CI: 3.093-4.703, P<0.001; OR=2.642, 95% CI: 2.152-3.242, P<0.001; OR=2.882, 95% CI: 2.347-3.539, P<0.001; respectively). Depression patients carrying C allele (TC+CC) of rs701848 and carrying T allele (AT+TT) of rs112025902 had higher HAMD total scores and HAMD anxiety factor scores than those carrying TT genotype of rs701848 and carrying AA genotype of rs112025902 (all P<0.05). Furthermore, depression patients carrying C allele (GC+CC) of rs2735343 had lower HAMD total scores and HAMD factors associated with depression scores than those carrying GG genotype (both P<0.05). Logistic regression analysis revealed that rs701848, rs2735343 and rs112025902 polymorphisms in the PTEN gene may be independent risk factors of depression (relative risk [RR]=1.807, 95% CI=1.023-3.193, P=0.042; RR=1.759, 95% CI=1.033-2.995, P=0.038; RR=1.646, 95% CI=1.018-2.663, P=0.042; respectively). CONCLUSION: Our findings provide evidence that rs701848, rs2735343 and rs112025902 polymorphisms in the PTEN gene may be correlated with the risk of depression and depressive symptoms in the Chinese population. PMID- 27677224 TI - Addressing the misdiagnosis of asthma in adults: where does it go wrong? AB - INTRODUCTION: Asthma is diagnosed based on patients' respiratory symptoms of wheeze, cough, chest tightness and/or dyspnea together with physiologic evidence of variable and reversible expiratory airflow limitation. A high prevalence of overdiagnosis, underdiagnosis and misdiagnosis of adult asthma has been reported in the literature. Areas covered: Misdiagnosis of asthma in adults can occur in the community due to physicians' failure to confirm airflow limitation using spirometry, the relatively poor sensitivity of spirometry to absolutely rule in asthma, the complexity of multiple asthma phenotypes and endotypes, and the inherent day to day variability of asthma symptoms and airflow limitation. Consequences of asthma misdiagnosis to the patient and to the healthcare system include increased medication costs, increased potential side effects related to unnecessary use of medications and lost opportunities to diagnose the true cause of patients' respiratory symptoms. Expert commentary: Here we provide a review of the problem of misdiagnosis of adult asthma and suggestions for how to decrease the risk of misdiagnosis. PMID- 27677223 TI - A novel homozygous variant in SERPINH1 associated with a severe, lethal presentation of osteogenesis imperfecta with hydranencephaly. AB - Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance. However, within the last two decades, there have been growing number of variants identified in genes that follow an autosomal recessive pattern of inheritance. Our proband is a child born in Mexico with multiple fractures of ribs, minimal calvarial mineralisation, platyspondyly, marked compression and deformed long bones. He also presented with significant hydranencephaly, requiring ventilatory support from birth, and died at 8days of age. A homozygous c.338_357delins22 variant in exon 2 of SERPINH1 was identified. This gene encodes heat shock protein 47, a collagen-specific chaperone which binds to the procollagen triple helix and is responsible for collagen stabilisation in the endoplasmic reticulum. There is minimal literature on the mechanism of action for variants in SERPINH1 resulting in osteogenesis imperfecta. Here we discuss this rare, previously unreported variant, and expand on the phenotypic presentation of this novel variant resulting in a severe, lethal phenotype of OI in association with hydranencephaly. PMID- 27677225 TI - beta-Blockers in Decompensated Cirrhosis: More Questions Than Answers. PMID- 27677226 TI - The role of endosomal toll-like receptors in asthma. AB - Asthma is a heterogeneous inflammatory disease caused by association of genetic and environmental factors and its incidence has significantly increased over the latest years. The clinical manifestations of asthma are the result of airway hyper-reactivity to a variety of triggers such as aeroallergens, viral and bacterial components. Toll-like receptors (TLRs) are pathogen associated molecular pattern receptors, which are also expressed in the lung tissue as well as in several cells of the innate and adaptive immune system. Ligation of TLRs results in alterations in the expression of several inflammatory and anti inflammatory mediators, which are known to be involved in the pathogenesis of asthma. The endosomal TLRs have been shown to be associated with the induction of asthmatic inflammation (TLR3), and with disease exacerbations (TLR7, TLR8 and TLR9). Targeting these receptors seems to be an effective choice for suppressing airway inflammation, eosinophilia and airway hyperresponsiveness in asthmatic patients. In this review we provide information regarding endosomal TLRs and their role in the pathogenesis of asthma as well as their potential use as targets for the development of novel treatments for the therapy of asthma. PMID- 27677227 TI - Realizing topological stability of magnetic helices in exchange-coupled multilayers for all-spin-based system. AB - Topologically stabilized spin configurations like helices in the form of planar domain walls (DWs) or vortex-like structures with magnetic functionalities are more often a theoretical prediction rather than experimental realization. In this paper we report on the exchange coupling and helical phase characteristics within Dy-Fe multilayers. The magnetic hysteresis loops with temperature show an exchange bias field of around 1.0 kOe at 10 K. Polarized neutron reflectivity reveal (i) ferrimagnetic alignment of the layers at low fields forming twisted magnetic helices and a more complicated but stable continuous helical arrangement at higher fields (ii) direct evidence of helices in the form of planar 2pi-DWs within both layers of Fe and Dy. The helices within the Fe layers are topologically stabilized by the reasonably strong induced in-plane magnetocrystalline anisotropy of Dy and the exchange coupling at the Fe-Dy interfaces. The helices in Dy are plausibly reminiscent of the helical ordering at higher temperatures induced by the field history and interfacial strain. Stability of the helical order even at large fields have resulted in an effective modulation of the periodicity of the spin-density like waves and subsequent increase in storage energy. This opens broad perspectives for future scientific and technological applications in increasing the energy density for systems in the field of all-spin-based engineering which has the potential for energy storing elements on nanometer length scales. PMID- 27677228 TI - Bone Morphogenetic Protein-7 Antagonizes Myocardial Fibrosis Induced by Atrial Fibrillation by Restraining Transforming Growth Factor-beta (TGF-beta)/Smads Signaling. AB - BACKGROUND This aim of this study was to investigate the expression of BMP-7 in atrial fibrillation and illuminate the role of BMP-7 and TGF-beta/Smads signaling in myocardial fibrosis. MATERIAL AND METHODS Fibrosis of myocardial fibroblasts was induced by TGF-beta1 and the optimal condition was determined by the MTT assay. Cells with TGF-beta1 treatment were sub-divided into 4 groups: TGF-beta1 group, TGF-beta1 + Smad3 siRNA group, TGF-beta1 + BMP-7 group, and TGF-beta1 + BMP-7 + Smad1/5 siRNA group. Cells were then analyzed by detecting the expression of epithelial cadherin (E-cadherin), collagen I, alpha smooth muscle cell actin (alpha-SMA), and activated Smads using Western blot. Mice were injected daily with Ach-CaCl2 with or without the addition of BMP-7 and Smad1/5 siRNA over a period of 4 weeks. Cardiac functions were tested by echocardiogram assay and fibrosis was diagnosed by histopathological examination. Finally, molecule biomarkers were detected using standard procedures. RESULTS TGF-beta1 treatment significantly down-regulated E-cadherin expression and up-regulated expressions of Collagen I, alpha-SMA, and pSmad3 (P<0.05). The effects of TGF-beta1 treatment can be significantly suppressed by Smad3 siRNA (P<0.05). Cells in the BMP-7 group exhibited significantly higher expression levels of E-cadherin and pSmad1/5 together with lower expression levels of pSmad3, collagen I, and a-SMA (P<0.05). Moreover, Smad1/5 siRNA can substantially repress the effects of BMP-7 (P<0.05) and results from the mice model coincided with those in myocardial fibroblasts. CONCLUSIONS BMP-7 can regulate TGF-beta1/Smad3 by targeting Smad1/5 to antagonize fibrosis in myocardial fibroblasts resulting from atrial fibrillation. PMID- 27677229 TI - Risk factors for acute toxoplasmosis in England and Wales. AB - Over 300 cases of acute toxoplasmosis are confirmed by reference testing in England and Wales annually. We conducted a case-control study to identify risk factors for Toxoplasma gondii infection to inform prevention strategies. Twenty eight cases and 27 seronegative controls participated. We compared their food history and environmental exposures using logistic regression to calculate odds ratios (OR) and 95% confidence intervals in a model controlling for age and sex. Univariable analysis showed that the odds of eating beef (OR 10.7, P < 0.001), poultry (OR 6.4, P = 0.01) or lamb/mutton (OR 4.9, P = 0.01) was higher for cases than controls. After adjustment for potential confounders a strong association between beef and infection remained (OR 5.6, P = 0.01). The small sample size was a significant limitation and larger studies are needed to fully investigate potential risk factors. The study findings emphasize the need to ensure food is thoroughly cooked and handled hygienically, especially for those in vulnerable groups. PMID- 27677230 TI - Calcification response of a key phytoplankton family to millennial-scale environmental change. AB - Coccolithophores are single-celled photosynthesizing marine algae, responsible for half of the calcification in the surface ocean, and exert a strong influence on the distribution of carbon among global reservoirs, and thus Earth's climate. Calcification in the surface ocean decreases the buffering capacity of seawater for CO2, whilst photosynthetic carbon fixation has the opposite effect. Experiments in culture have suggested that coccolithophore calcification decreases under high CO2 concentrations ([CO2(aq)]) constituting a negative feedback. However, the extent to which these results are representative of natural populations, and of the response over more than a few hundred generations is unclear. Here we describe and apply a novel rationale for size-normalizing the mass of the calcite plates produced by the most abundant family of coccolithophores, the Noelaerhabdaceae. On average, ancient populations subjected to coupled gradual increases in [CO2(aq)] and temperature over a few million generations in a natural environment become relatively more highly calcified, implying a positive climatic feedback. We hypothesize that this is the result of selection manifest in natural populations over millennial timescales, so has necessarily eluded laboratory experiments. PMID- 27677233 TI - [5-HT3-antagonists as a substitute for metoclopramide and domperidone: a literature review]. AB - OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron. These had to be randomised controlled clinical studies into the known indications for metoclopramide and domperidone for prevention and treatment of nausea and vomiting. Two reviewers independently selected articles based on the title and abstract, then assessed for eligibility based on the full texts. RESULTS: In total, 56 articles were included in this review. The conclusion in 51 studies was that the efficacy of 5-HT3-antagonists in nausea and vomiting is comparable or even superior to that of metoclopramide. Metoclopramide more often caused extrapyramidal side effects; 5-HT3-antagonists were more likely to cause headaches and constipation. The majority of the studies compared metoclopramide with ondansetron. None of the articles studied palonosetron, and only one study compared domperidone with a 5-HT3-antagonist. CONCLUSION: We found enough evidence to presume that metoclopramide can be replaced by 5-HT3-antagonists for preventing delayed chemotherapy-induced nausea and vomiting and for prophylaxis or treatment of postoperative nausea and vomiting. More research is needed into the other indications and into the substitutability of domperidone. PMID- 27677231 TI - Neural mechanisms of cue-approach training. AB - Biasing choices may prove a useful way to implement behavior change. Previous work has shown that a simple training task (the cue-approach task), which does not rely on external reinforcement, can robustly influence choice behavior by biasing choice toward items that were targeted during training. In the current study, we replicate previous behavioral findings and explore the neural mechanisms underlying the shift in preferences following cue-approach training. Given recent successes in the development and application of machine learning techniques to task-based fMRI data, which have advanced understanding of the neural substrates of cognition, we sought to leverage the power of these techniques to better understand neural changes during cue-approach training that subsequently led to a shift in choice behavior. Contrary to our expectations, we found that machine learning techniques applied to fMRI data during non-reinforced training were unsuccessful in elucidating the neural mechanism underlying the behavioral effect. However, univariate analyses during training revealed that the relationship between BOLD and choices for Go items increases as training progresses compared to choices of NoGo items primarily in lateral prefrontal cortical areas. This new imaging finding suggests that preferences are shifted via differential engagement of task control networks that interact with value networks during cue-approach training. PMID- 27677234 TI - [Real change or natural fluctuation?] AB - When monitoring patients over time, it may be difficult to distinguish 'real changes' from so-called 'natural fluctuations' when interpreting consecutive laboratory results. Consider a patient whose cholesterol level has decreased from a baseline 6.6 mmol/L to 6.1 mmol/L six months after receiving lifestyle advice. How likely is it that this is a 'real change', reflecting a lifestyle change, rather than random fluctuation? Physicians mostly rely on their intuition and clinical experience when interpreting changes in consecutive laboratory results. For inexperienced physicians, the lack of an easy reference for the interpretation of consecutive laboratory results can make decision-making challenging. We have developed the medical/educational smartphone app Labtracker+ that calculates the probability of a 'real change' between two consecutive laboratory results, using biological variation data from scientific literature and analytical precision that is achieved in contemporary laboratories. This approach may complement intuitive, experience-based interpretations of consecutive laboratory results. PMID- 27677232 TI - Event-related potentials elicited during working memory are altered in mild cognitive impairment. AB - Persons with Mild Cognitive Impairment (MCI) can experience deficits in working memory. In the present study, we investigated working memory in persons with MCI and cognitively healthy older adults using event-related potentials (ERPs). Participants performed an n-back working memory task with baseline (0-back), low load (1-back), and high load (2-back) working memory conditions. MCI participants' performance was less accurate than that of healthy older adults in both the 1-back and 2-back conditions, and reaction times were longer in MCI than control participants in the 0-back, 1-back and 2-back conditions. ERP analyses revealed delayed P200 and N200 latencies and smaller P300 amplitudes in MCI relative to control participants in the 0-back, 1-back and 2-back conditions. Deterioration in working memory performance concomitant with marked electrophysiological alterations suggests that persons with MCI exhibit deficits in several cognitive processes that include early attention, stimulus discrimination and classification, and updating and manipulation of information held in working memory. PMID- 27677236 TI - [Amoxicillin and paracetamol dosing in children: playing safe]. AB - Amoxicillin and paracetamol are the two most widely prescribed and recommended medicines in children. Due to lack of scientific evidence of the most effective dosage, dosing instructions of both medicines are often unclear. In this article we challenge general practitioners, paediatricians, child-health clinic physicians, ENT specialists, pharmacists and guideline committees to critically evaluate the current dosing instructions of these two medicines. The Netherlands paediatric formulary, the Kinderformularium, should become the primary formulary for children in the Netherlands, but it has to be more in line with daily practice, and basic dosing instructions should be less ambiguous: (a) dosing instructions based on body weight instead of age; b) in case of pain, paracetamol should be given 60 mg/kg/day in four divided doses; (c) in case of common uncomplicated infections, amoxicillin should be given orally 60 mg/kg/day in two divided doses; (d) the following should be mentioned on the antibiotic prescription: the daily dose, the number of divided doses, the duration of therapy, the indication for the prescription, and the child's weight. This will result in safe prescription of medicines for children, with fewer unnecessary disruptive consultations between prescriber and pharmacist. PMID- 27677235 TI - [Stress fracture or osteochondral lesion of the navicular bone?] AB - BACKGROUND: An osteochondral lesion of the navicular bone in the foot is rare. Differentiation from a stress fracture is difficult, since both lesions usually present as vague pain in the midfoot in active young adults. However, the typical location differs. SPECT-CT allows an etiological diagnosis to be made. As management differs for the two lesions, a correct diagnosis is important. CASE DESCRIPTION: A 19-year-old male athlete had pain in the dorsal right midfoot on weight-bearing. A diagnosis of 'stress fracture of the navicular bone' was made on the basis of SPECT-CT. Since conservative therapy did not help, and because the location was atypical for a stress fracture, the diagnosis was revised to 'osteochondral lesion'. CONCLUSION: The key to the diagnosis of osteochondral lesion is its location in the central proximal third of the navicular bone. Patients with this type of lesion often undergo surgical treatment, whereas conservative therapy is sufficient in case of a stress fracture. PMID- 27677237 TI - [Cutaneous leishmaniasis in a Syrian refugee]. AB - BACKGROUND: Cutaneous leishmaniasis is rare in the Netherlands, but it is endemic to Syria. The disease can manifest itself many years after initial exposure. Given the arrival of Syrian refugees in the Netherlands, awareness of this disease entity is warranted. CASE DESCRIPTION: A 5-year-old boy from Syria had investigations for hepatosplenomegaly. As an incidental finding a solitary, moderately demarcated, erythematous plaque was noted on his right cheek. It measured 4 * 2 cm and had a central haemorrhagic, exudative, honey-yellow slough. Due to the hepatosplenomegaly, as well as cutaneous leishmaniasis we also included its visceral form in the differential diagnosis. Additional investigations confirmed the diagnosis of cutaneous leishmaniasis. CONCLUSION: Given the rising incidence of leishmaniasis in Syria, the diagnosis of cutaneous leishmaniasis should be considered in a Syrian refugee who has an ulcerating nodule or plaque. A timely local treatment may improve long-term cosmetic outcome. PMID- 27677238 TI - An electrical probe of the phonon mean-free path spectrum. AB - Most studies of the mean-free path accumulation function (MFPAF) rely on optical techniques to probe heat transfer at length scales on the order of the phonon mean-free path. In this paper, we propose and implement a purely electrical probe of the MFPAF that relies on photo-lithographically defined heater-thermometer separation to set the length scale. An important advantage of the proposed technique is its insensitivity to the thermal interfacial impedance and its compatibility with a large array of temperature-controlled chambers that lack optical ports. Detailed analysis of the experimental data based on the enhanced Fourier law (EFL) demonstrates that heat-carrying phonons in gallium arsenide have a much wider mean-free path spectrum than originally thought. PMID- 27677239 TI - Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments. AB - Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme-inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases. PMID- 27677240 TI - Near-infrared roll-off-free electroluminescence from highly stable diketopyrrolopyrrole light emitting diodes. AB - Organic light emitting diodes (OLEDs) operating in the near-infrared spectral region are gaining growing relevance for emerging photonic technologies, such as lab-on-chip platforms for medical diagnostics, flexible self-medicated pads for photodynamic therapy, night vision and plastic-based telecommunications. The achievement of efficient near-infrared electroluminescence from solution processed OLEDs is, however, an open challenge due to the low photoluminescence efficiency of most narrow-energy-gap organic emitters. Diketopyrrolopyrrole-boron complexes are promising candidates to overcome this limitation as they feature extremely high photoluminescence quantum yield in the near-infrared region and high chemical stability. Here, by incorporating suitably functionalized diketopyrrolopyrrole derivatives emitting at ~760 nm in an active matrix of poly(9,9-dioctylfluorene-alt-benzothiadiazole) and without using complex light out-coupling or encapsulation strategies, we obtain all-solution-processed NIR OLEDs with external quantum efficiency as high as 0.5%. Importantly, our test-bed devices show no efficiency roll-off even for high current densities and high operational stability, retaining over 50% of the initial radiant emittance for over 50 hours of continuous operation at 10 mA/cm2, which emphasizes the great applicative potential of the proposed strategy. PMID- 27677241 TI - First North American experience with the transfemoral ACURATE-neoTM self expanding transcatheter aortic bioprosthesis. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become a therapeutic alternative for patients presenting with severe symptomatic aortic stenosis and considered at high-surgical risk. Paravalvular leak (PVL), conduction disorders, and coronary obstruction remain unresolved procedure related complications. The aim of this manuscript was to report the first North American experience with the ACURATE-neoTM aortic bioprosthesis and its ACURATE TFTM delivery system (Symetis S.A., Ecublens, Switzerland). METHODS: Transfemoral ACURATE-neoTM aortic valve implantation was performed in 20 patients. Clinical and echocardiographic assessment was performed at baseline, postprocedure and at least 30 days. Outcomes were assessed according to valvular academic research consortium (VARC-2) criteria. RESULTS: The mean age was 82.7 +/- 7.0 years with a mean logistic-EuroSCORE-II of 5.0 +/- 2.9% and Society of Thoracic Surgeons score of 4.7 +/- 2.3%. Device success was achieved in all patients. The mean distance between the aortic-annulus and the left main coronary artery ostium was 14.3 +/- 3.2 mm, and eight (40%) patients had <12 mm. At 30 days, there were no deaths, conversions to surgery, or major procedure-related complications. New-pacemaker implantation was required in one (5.3%) patient. ACURATE-neoTM implantation resulted in a significant reduction in mean transvalvular gradient (49.9 +/- 15.8 to 9.7 +/- 5.7 mm Hg, P < 0.0001) and increase in effective-orifice area (0.65 +/ 0.16 to 1.83 +/- 0.36 cm2 , P = 0.001) at hospital discharge. Paravalvular leak was absent in four (20%) patients, trace in nine (45%) patients, and mild in seven (35%) patients. Hospital discharge occurred at a mean of 7.0 +/- 4.5 days, and all patients were in NYHA class I-II at a mean follow-up of 8.6 +/- 2.3 months. CONCLUSION: The present initial North American experience shows that the ACURATE-neoTM aortic bioprosthesis was safely and successfully implanted by transfemoral approach. The special design of this newer-generation device affords a stable and predictable implantation, while providing optimal hemodynamic performance with a relatively low rate of PPI. (c) 2016 Wiley Periodicals, Inc. PMID- 27677242 TI - Neoadjuvant Chemoradiotherapy vesus Chemotherapy alone Followed by Surgery for Resectable Stage III Non-Small-Cell Lung Cancer: a Meta-Analysis. AB - Neoadjuvant Chemotherapy has been used for the stage III of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, the survival benefits of radiation therapy added in induction regimens remains controversial. We therefore conducted a meta-analysis of the published clinical trials to quantitatively evaluate the benefit of preoperative chemoradiotherapy. After searching the database of Pubmed, CNKI, EMBASE, ESMO, The Cochrane Library databases, The American Society of Clinical Oncology and Clinical Trials.gov. Trials were selected for meta-analysis if they provided an independent assessment of neoadjuvant chemoradiation and neoadjuvant chemotherapy, odds ratio(OR) for tumor downstaging, mediastinal lymph nodes pathological complete response and local control, hazard ratios (HRs) for 5-year survival and progression-free survival were pooled by the stata software version 12.0. Twelve studies involving 2,724 patients were identified, tumor downstaging (p = 0.01), mediastinal lymph nodes pathological complete responses (p = 0.028) and local control (P = 0.002) were achieved, when compared with neoadjuvant chemotherapy. The meta-analysis demonstrated neither 5-year survival nor progression-free-survival benefit in survival from adding radiation. In conclusion, the addition of radiotherapy into chemotherapy was not superior to neoadjuvant chemotherapy. The higher quality of trials need be investigated combining with the histopathological type and genotyping of lung cancer by clinicians. PMID- 27677243 TI - Insulin enhanced leptin-induced STAT3 signaling by inducing GRP78. AB - Leptin, an adipocyte-derived hormone, centrally regulates energy homeostasis. Overlaps in the regulation of glucose and energy homeostasis have been reported between leptin and insulin. However, the effects of insulin on leptin's actions in the central nervous system (CNS) have not yet been elucidated in detail. In the present study, we found that insulin potentiated leptin's actions through GRP78 in the neuronal cell line, SH-SY5Y-ObRb. Since insulin induces GRP78, we speculated that it may also enhance leptin's actions through this induction. We found that insulin enhanced leptin-induced STAT3 phosphorylation and this effect was ameliorated by the knockdown of GRP78. The role of GRP78 in leptin's actions was also confirmed by impairments in leptin-induced STAT3 phosphorylation in HEK293-ObRb cells in which GRP78 was knocked down. Furthermore, we found that the overexpression of GRP78 enhanced leptin-induced STAT3 phosphorylation. These results suggest that GRP78 plays an important role in leptin's actions. Furthermore, insulin may enhance the leptin-induced activation of STAT3 by inducing GRP78, which may provide an important connection between insulin and leptin in the CNS. PMID- 27677244 TI - Forward design of a complex enzyme cascade reaction. AB - Enzymatic reaction networks are unique in that one can operate a large number of reactions under the same set of conditions concomitantly in one pot, but the nonlinear kinetics of the enzymes and the resulting system complexity have so far defeated rational design processes for the construction of such complex cascade reactions. Here we demonstrate the forward design of an in vitro 10-membered system using enzymes from highly regulated biological processes such as glycolysis. For this, we adapt the characterization of the biochemical system to the needs of classical engineering systems theory: we combine online mass spectrometry and continuous system operation to apply standard system theory input functions and to use the detailed dynamic system responses to parameterize a model of sufficient quality for forward design. This allows the facile optimization of a 10-enzyme cascade reaction for fine chemical production purposes. PMID- 27677245 TI - Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results. AB - It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms. PMID- 27677247 TI - Intramyocardial lipoma. PMID- 27677246 TI - Vascular patterns in the heads of crocodilians: blood vessels and sites of thermal exchange. AB - Extant crocodilians are a highly apomorphic archosaur clade that is ectothermic, yet often achieve large body sizes that can be subject to higher heat loads. Therefore, the anatomical and physiological roles that blood vessels play in crocodilian thermoregulation need further investigation to better understand how crocodilians establish and maintain cephalic temperatures and regulate neurosensory tissue temperatures during basking and normal activities. The cephalic vascular anatomy of extant crocodilians, particularly American alligator (Alligator mississippiensis) was investigated using a differential-contrast, dual vascular injection technique and high resolution X-ray micro-computed tomography (MUCT). Blood vessels were digitally isolated to create representations of vascular pathways. The specimens were then dissected to confirm CT results. Sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in evaporative cooling and cephalic thermoregulation in other diapsids. Blood vessels to and from sites of thermal exchange were studied to detect conserved vascular patterns and to assess their ability to deliver cooled blood to neurosensory tissues. Within the orbital region, both the arteries and veins demonstrated consistent branching patterns, with the supraorbital, infraorbital, and ophthalmotemporal vessels supplying and draining the orbit. The venous drainage of the orbital region showed connections to the dural sinuses via the orbital veins and cavernous sinus. The palatal region demonstrated a vast plexus that comprised both arteries and veins. The most direct route of venous drainage of the palatal plexus was through the palatomaxillary veins, essentially bypassing neurosensory tissues. Anastomotic connections with the nasal region, however, may provide an alternative route for palatal venous blood to reach neurosensory tissues. The nasal region in crocodilians is probably the most prominent site of thermal exchange, as it offers a substantial surface area and is completely surrounded by blood vessels. The venous drainage routes from the nasal region offer routes directly to the dural venous sinuses and the orbit, offering evidence of the potential to directly affect neurosensory tissue temperatures. The evolutionary history of crocodilians is complex, with large-bodied, terrestrial, and possibly endothermic taxa that may have had to deal with thermal loads that likely provided the anatomical building-blocks for such an extensive vascularization of sites of thermal exchange. A clear understanding of the physiological abilities and the role of blood vessels in the thermoregulation of crocodilians neurosensory tissues is not available but vascular anatomical patterns of crocodilian sites of thermal exchange indicate possible physiological abilities that may be more sophisticated than in other extant diapsids. PMID- 27677248 TI - Neural Progenitor Cells Rptor Ablation Impairs Development but Benefits to Seizure-Induced Behavioral Abnormalities. AB - AIMS: Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities. METHODS: Mice with conditional knockout of raptor protein were generated by cross bred Rptorflox/flox mice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively. Spontaneous seizures were recorded by EEG-video system. Morris water maze, open field test, and excitability test were used to study the behaviors of Rptor CKO mice. RESULTS: As the consequence of deleting Rptor, downstream proteins of raptor in mTORC1 signaling were partly blocked. Rptor CKO mice exhibited decrease in body and brain weight under 7 weeks old and accordingly, cortical layer thickness. After kainic acid (KA)-induced status epilepticus, overactivation of mTORC1 signaling was markedly reversed in Rptor CKO mice. Although low frequency of spontaneous seizure and seldom neuronal cell death were observed in both Rptor CKO and control littermates, KA seizure-induced mossy fiber spouting were attenuated in Rptor CKO mice. Additionally, cognitive deficit and anxiety-like behavior after KA-induced seizures were partly reversed in Rptor CKO mice. CONCLUSION: Loss of the Rptor gene in mice neural progenitor cells affects normal development in young age and may contribute to alleviate KA seizure-induced behavioral abnormalities, suggesting that raptor protein plays an important role in seizure comorbidities. PMID- 27677249 TI - The decline in synaptic GluN2B and rise in inhibitory neurotransmission determine the end of a critical period. AB - Neuronal plasticity is especially active in the young, during short windows of time termed critical periods, and loss of a critical period leads to functional limitations in the adults. The mechanism that governs the length of critical periods remains unknown. Here we show that levels of the NMDA receptor GluN2B subunit, which functions as a Ca2+ channel, declines in spinal cord synapses toward the end of the critical period for activity-dependent corticospinal synapse elimination. This period could be prolonged by blocking the decline of GluN2B, and after its termination the critical period could be reopened through upregulation of GluN2B. It is known that inhibitory neural activity increases with development in the CNS including the spinal cord. Suppression of the increasing inhibitory activity using low-dose strychnine also prolonged this critical period. During the strychnine-widened time window, Ca2+ influx through GluN2B channels returned to a level comparable to that seen during the critical period, though the level of GluN2B was slightly reduced. These findings indicate that loss of GluN2B subunits and the associated reduction in Ca2+ influx determines the end of the critical period in our in vitro CS system. PMID- 27677250 TI - Clinical pharmacists' opportunities to reduce inappropriate prescription of QT prolonging medications: calls to action. AB - All biologically active agents carry the potential to lead to adverse reactions in certain individuals, including serious cardiac adverse reactions. Since 2005, there has been an international regulatory landscape governing the investigation of a new drug's propensity to lead to the polymorphic ventricular tachycardia Torsades de Pointes (Torsades), a rare but potentially fatal occurrence. When a regulatory agency considers it appropriate, warning information is placed in a medicine's patient information leaflet (label) concerning drug-induced QT interval prolongation, a phenomenon associated with Torsades. In busy hospital settings, however, prescribers, including cardiologists, make injudicious prescribing decisions that put patients at risk. The science of cardiac safety, including the clinical trials that generate the information about QT prolongation in patient information leaflets, is frequently not part of the curriculum at Schools of Pharmacy. Given that medication-induced cardiotoxicity is extremely serious, we advocate that schools integrate the science of cardiac safety into existing therapeutics/therapeutic medication monitoring courses. Given their expert knowledge of pharmacology, pharmacists working as part of a hospital's clinical team would then be even better placed to review prescribing decisions concerning medications that prolong the QT interval, and alert prescribers in cases where reassessing their decisions seems prudent. National pharmacy societies or other pertinent professional societies could create practice guidelines to support graduates once employed as clinical pharmacists. Clinical pharmacists are well placed to be influential arbiters of safer prescribing decisions. Cardiac safety education during their pharmacy training and practice guideline support from professional societies during their careers can optimize this role. PMID- 27677251 TI - Discovery of Escherichia coli CRISPR sequences in an undergraduate laboratory. AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) represent a novel type of adaptive immune system found in eubacteria and archaebacteria. CRISPRs have recently generated a lot of attention due to their unique ability to catalog foreign nucleic acids, their ability to destroy foreign nucleic acids in a mechanism that shares some similarity to RNA interference, and the ability to utilize reconstituted CRISPR systems for genome editing in numerous organisms. In order to introduce CRISPR biology into an undergraduate upper-level laboratory, a five-week set of exercises was designed to allow students to examine the CRISPR status of uncharacterized Escherichia coli strains and to allow the discovery of new repeats and spacers. Students started the project by isolating genomic DNA from E. coli and amplifying the iap CRISPR locus using the polymerase chain reaction (PCR). The PCR products were analyzed by Sanger DNA sequencing, and the sequences were examined for the presence of CRISPR repeat sequences. The regions between the repeats, the spacers, were extracted and analyzed with BLASTN searches. Overall, CRISPR loci were sequenced from several previously uncharacterized E. coli strains and one E. coli K-12 strain. Sanger DNA sequencing resulted in the discovery of 36 spacer sequences and their corresponding surrounding repeat sequences. Five of the spacers were homologous to foreign (non-E. coli) DNA. Assessment of the laboratory indicates that improvements were made in the ability of students to answer questions relating to the structure and function of CRISPRs. Future directions of the laboratory are presented and discussed. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):262-269, 2017. PMID- 27677252 TI - Efficient Self-Contained Photoacid Generator System Based on Photochromic Terarylenes. AB - A series of highly sensitive neutral photoacid generators (PAGs) based on photochromic terarylenes was prepared. Like the example presented herein, these compounds show a subsequent thermal elimination of a Bronsted acid after a light triggered 6pi-electrocyclization, concomitant with the hexatriene aromatization. A novel type of molecular systems was developed, in which one thiazolyl moiety was replaced by a thienyl group. Depending on the solvents and on the nature of the acid source, the quantum yield (QY) for acid generation could reach up to 0.6. Comparative studies on the acid source clearly showed that aromatic leaving groups tend to extinguish the molecular system photoefficiency. A second type was also prepared, in which the nature of the hetero-aromatic rings were identical to our previous example, but their sequence was modified. Therefore, a second level of improvement was achieved in nonpolar solvents, pushing the QY value up to 0.7. Finally, we demonstrated the mesylic acid-releasing PAG as a photocatalyst in a chemically amplified positive resist system. PMID- 27677254 TI - Graphene Glass from Direct CVD Routes: Production and Applications. AB - Recently, direct chemical vapor deposition (CVD) growth of graphene on various types of glasses has emerged as a promising route to produce graphene glass, with advantages such as tunable quality, excellent film uniformity and potential scalability. Crucial to the performance of this graphene-coated glass is that the outstanding properties of graphene are fully retained for endowing glass with new surface characteristics, making direct-CVD-derived graphene glass versatile enough for developing various applications for daily life. Herein, recent advances in the synthesis of graphene glass, particularly via direct CVD approaches, are presented. Key applications of such graphene materials in transparent conductors, smart windows, simple heating devices, solar-cell electrodes, cell culture medium, and water harvesters are also highlighted. PMID- 27677253 TI - Lactose malabsorption in systemic sclerosis. AB - BACKGROUND: There are no studies on systemic sclerosis (SSc) assessing the relationship between food intake, especially lactose, and gastrointestinal dysfunction. AIM: To determine the prevalence of lactose malabsorption, using lactose breath test, in patients with SSc. To evaluate the correlation between lactose malabsorption and gastrointestinal involvement. To predict which SSc patients exhibit lactose malabsorption. METHODS: Seventy-seven consecutive Caucasian patients with SSc and 20 control subjects underwent lactose breath test. All patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. RESULTS: The prevalence of lactose malabsorption was higher in SSc patients than in controls (44.3% vs. 10%; P = 0.004). We observed a marked correlation between the presence of lactose malabsorption and: higher values of GSS (P < 0.0001); severe oesophageal (P = 0.018) and small intestinal (P = 0.04) motor disorders; and joint involvement (P = 0.019). Furthermore, in SSc patients with symptomatic lactose malabsorption, the median value of GSS of digestive symptoms was lower after initiation of lactose-free diet (P < 0.0001). CONCLUSIONS: Our study underscores the fact that lactose malabsorption often occurs in patients with systemic sclerosis. Furthermore, our findings highlight the fact that lactose breath test is a helpful, noninvasive method, by identifying the group of patients with systemic sclerosis with symptomatic lactose malabsorption that may benefit from a reduction in lactose intake. PMID- 27677255 TI - A functional variant at the miRNA binding site in E2F1 gene is associated with risk and tumor HPV16 status of oropharynx squamous cell carcinoma. AB - Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB1-E2F pathway. Genetic polymorphisms in the 3' untranslated region (UTR) targeted by miRNAs can affect the regulation of target genes and individual cancer risk. Thus, we hypothesized that a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) was associated with risk of oral squamous cell carcinoma (OSCC) and tumor HPV status of oropharynx squamous cell carcinoma (OPSCC). We determined the E2F1rs3213180 polymorphism and HPV16 L1 serology of 325 OSCC patients and 335 controls, and tumor HPV16 status of 552 OPSCC. Logistic regression models were used to calculate associations of E2F1rs3213180 polymorphism with risk of HPV associated OSCC and tumor HPV status of OPSCC. The risk of HPV-associated OSCC was modified by the E2F1rs3213180 polymorphism. Patients with both HPV seropositivity and the Ins/Del or Ins/Ins genotype of E2F1rs3213180 had the highest risk of OSCC, while the lowest risk was detected in patients with HPV seronegativity and the Del/Del genotype. A similar and more prominent effect was detected in OPSCC, but not in oral cavity squamous cell carcinoma (OCSCC) patients. Notably, that effect trend was pronounced in never-smokers and never drinkers. Furthermore, the patients with the E2F1rs3213180 Ins/Del or Ins/Ins genotype were 2.9 times more likely to have HPV-positive tumors than those with the Del/Del genotype. Our results suggest that the E2F1rs3213180 polymorphism may influence susceptibility to HPV-associated OSCC, particularly for OPSCC, never smokers and never-drinkers, but not for patients with OCSCC. Additional larger population and functional studies are warranted to confirm our findings. (c) 2016 Wiley Periodicals, Inc. PMID- 27677256 TI - Identification of a novel HLA allele, HLA-B*08:163, in a platelet donor. AB - The novel HLA-B*08:163 allele differs from HLA-B*08:01:01:01 by a single nucleotide substitution at codon 105. PMID- 27677257 TI - Similarities and differences between East and West in COPD. PMID- 27677258 TI - Time for a breath of fresh air: Rethinking training in airway management. PMID- 27677259 TI - Reporting studies on time to diagnosis: proposal of a guideline by an international panel (REST). AB - BACKGROUND: Studies on time to diagnosis are an increasing field of clinical research that may help to plan corrective actions and identify inequities in access to healthcare. Specific features of time to diagnosis studies, such as how participants were selected and how time to diagnosis was defined and measured, are poorly reported. The present study aims to derive a reporting guideline for studies on time to diagnosis. METHODS: Each item of a list previously used to evaluate the completeness of reporting of studies on time to diagnosis was independently evaluated by a core panel of international experts (n = 11) for relevance and readability before an open electronic discussion allowed consensus to be reached on a refined list. The list was then submitted with an explanatory document to first, last and/or corresponding authors (n = 98) of published systematic reviews on time to diagnosis (n = 45) for relevance and readability, and finally approved by the core expert panel. RESULTS: The refined reporting guideline consists of a 19-item checklist: six items are about the process of participant selection (with a suggested flowchart), six about the definition and measurement of time to diagnosis, and three about optional analyses of associations between time to diagnosis and participant characteristics and health outcomes. Of 24 responding authors of systematic reviews, more than 21 (>=88 %) rated the items as relevant, and more than 17 (>=70 %) as readable; 19 of 22 (86 %) authors stated that they would potentially use the reporting guideline in the future. CONCLUSIONS: We propose a reporting guideline (REST) that could help authors, reviewers, and editors of time to diagnosis study reports to improve the completeness and the accuracy of their reporting. PMID- 27677260 TI - GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition. AB - BACKGROUND: Neuropsychiatric disorders are common forms of disability in humans. Despite recent progress in deciphering the genetics of these disorders, their phenotypic complexity continues to be a major challenge. Mendelian neuropsychiatric disorders are rare but their study has the potential to unravel novel mechanisms that are relevant to their complex counterparts. RESULTS: In an extended consanguineous family, we identified a novel neuropsychiatric phenotype characterized by severe speech impairment, variable expressivity of attention deficit hyperactivity disorder (ADHD), and motor delay. We identified the disease locus through linkage analysis on 15q21.2, and exome sequencing revealed a novel missense variant in GNB5. GNB5 encodes an atypical beta subunit of the heterotrimeric GTP-binding proteins (Gbeta5). Gbeta5 is enriched in the central nervous system where it forms constitutive complexes with members of the regulator of G protein signaling family of proteins to modulate neurotransmitter signaling that affects a number of neurobehavioral outcomes. Here, we show that the S81L mutant form of Gbeta5 has significantly impaired activity in terminating responses that are elicited by dopamine. CONCLUSIONS: We demonstrate that these deficits originate from the impaired expression of the mutant Gbeta5 protein, resulting in the decreased ability to stabilize regulator of G protein signaling complexes. Our data suggest that this novel neuropsychiatric phenotype is the human equivalent of Gnb5 deficiency in mice, which manifest motor deficits and hyperactivity, and highlight a critical role of Gbeta5 in normal behavior as well as language and motor development in humans. PMID- 27677262 TI - Self-Nanoemulsifying Drug Delivery System of Coenzyme (Q10) with Improved Dissolution, Bioavailability, and Protective Efficiency on Liver Fibrosis. AB - The aim of our investigation is to develop and characterize self-nanoemulsifying drug delivery systems (SNEDDS) of CoQ10 to improve its water solubility, dissolution rate, and bioavailability, and then evaluate its biochemical and physiological effect on liver cirrhosis in rats compared with CoQ10 powder. SNEDDS are isotropic and thermodynamically stable mixture of oil, surfactant, co surfactant, and drug that form an oil/water nanoemulsion when added to aqueous phases with soft agitation. Upon administration, self-nanoemulsifying system becomes in contact with gastrointestinal fluid and forms o/w nanoemulsion by the aid of gastrointestinal motility. When the nanoemulsion is formed in the gastrointestinal tract, it presents the drug in a solubilized form inside small nano-sized droplets that provide a large surface area for enhancing the drug release and absorption. Solubility of CoQ10 in various oils, surfactants, and co surfactants were studied to identify the components of SNEDDS; pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsifying regions. CoQ10-loaded SNEDDS were prepared using isopropyl myristate as oil; Cremophor El, Labrasol, or Tween80 as surfactant; and Transcutol as co-surfactant. The amount of CoQ10 in each vehicle was 3%. The formulations that passed thermostability evaluation test were assessed for particle size analysis, morphological characterization, refractive index, zeta potential, viscosity, electroconductivity, drug release profile, as well as ex vivo permeability. Pharmacokinetics and hepatoprotective efficiency of the optimized SNEDDS of CoQ10 compared with CoQ10 suspension were performed. Results showed that all optimized formulae have the ability to form a good and stable nanoemulsion when diluted with water; the mean droplet size of all formulae was in the nanometric range (11.7-13.5 nm) with optimum polydispersity index values (0.2-0.21). All formulae showed negative zeta potential (-11.3 to -17.2), and maximum drug loading efficiency. One hundred percent of CoQ10 was released from most formulae within 30 min. One hundred percent of CoQ10 was permeated from all formulae through 10 h. The pharmacokinetic study in rabbits revealed a significant increase in bioavailability of CoQ10 SNEDDS to 2.1-fold compared with CoQ10 suspension after oral administration. Comparative effect of the optimized formulae on acute liver injury compared with CoQ10 powder was also studied; it was found that all the liver biochemical markers as alanine transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total protein (TP), and albumin were significantly improved at p < 0.05. Also, histochemical and histopthological studies confirm the biochemical results. Our results suggest the potential use of SNEDDS to increase the solubility of liphophilic drug as poorly water-soluble CoQ10 and improve its oral absorption, so it can be more efficient to improve liver damage compared to CoQ10 powder. These results demonstrated that CoQ10 SNEDDS inhibited thioacetamide (TAA)-induced liver fibrosis mainly through suppression of collagen production. PMID- 27677261 TI - Hunting for the ultimate liquid cancer biopsy - let the TEP dance begin. AB - Non-protein coding RNAs in different flavors (miRNAs, piRNAs, snoRNAs, lncRNAs, SHOT-RNAs), exosomes, large oncosomes, exoDNA and now tumor-educated platelets (TEPs) have emerged as crucial signal transmitting, transporting and regulating devices of cells in the last two decades. They are also establishing themselves increasingly in the realm of tumor research. We are currently witnessing a mushrooming of candidate entities for diagnostic and prognostic cancer detection and characterization tests that could have a major impact on how this diverse group of diseases is initially spotted and subsequently treated in the near future. But how do the new kids on the block stand up to the more established circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)? Without question, much earlier disease detection would be expected to save numerous lives. With all these new players around, will we finally win a major battle in the never-ending war against cancer? PMID- 27677263 TI - Atazanavir and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Patients: A Systematic Review. AB - INTRODUCTION: Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular disease (CVD). While viral suppression with antiretroviral therapy decreases CVD risk overall, several studies have suggested that certain antiretrovirals, particularly certain protease inhibitors, may be associated with an increased relative risk of CVD. In AIDS Clinical Trials Group 5260 s, ritonavir-boosted atazanavir (ATV) was associated with slower atherosclerosis progression compared to ritonavir-boosted darunavir and raltegravir, potentially due to hyperbilirubinemia. Although hyperbilirubinemia may lead to increased rates of treatment discontinuation, it may also contribute to a favorable cardiovascular (CV) profile for ATV. To fully elucidate the effect of ATV on CVD risk among HIV-infected patients, a systematic review of the literature was performed. METHODS: A systematic search of the PubMed and Embase databases was conducted on August 26, 2015, using terms to identify papers that discuss ATV, HIV, and CVD. Articles were limited to English-language publications of randomized-controlled or observational studies investigating adult humans. The primary outcome was the incidence of CVD. Articles describing surrogate markers of CVD were also included. RESULTS: Ten studies were included in this qualitative analysis: six reported CVD outcomes, two reported data on atherosclerosis as assessed by carotid intima-media thickness (cIMT), and two reported outcomes related to endothelial function. The studies reporting the incidence of myocardial infarction (MI) among HIV-infected patients showed that ATV (boosted and unboosted) was not associated with an increased risk of acute MI. Other CV endpoints were similarly unaffected by treatment with ATV. Compared with non-ATV based regimens, ATV had beneficial effects on cIMT progression in the publications identified, with no apparent impact on endothelial function. CONCLUSIONS: This analysis showed that there was no increased risk or occurrence of adverse CV events among HIV-infected patients receiving ATV. Markers of atherosclerosis were improved, suggesting a possible antioxidant effect of ATV, and endothelial function was not affected. FUNDING: Bristol-Myers Squibb (article processing charges and medical writing support). PMID- 27677264 TI - Pre-exposure Prophylaxis for HIV Prevention: Why, What, Who and How. AB - Pre-exposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. It is protective against HIV infection across populations and has few significant safety risks and little evidence of behavioural risk compensation. This article summarises the evidence behind HIV PrEP as an intervention, populations that may benefit, current guidelines and programmes, and the cost effectiveness modelling of this strategy. PMID- 27677265 TI - Locomotive syndrome is associated with body composition and cardiometabolic disorders in elderly Japanese women. AB - BACKGROUND: A concept referred to as locomotive syndrome (LS) was proposed by the Japanese Orthopaedic Association in order to help identify middle-aged and older adults who may be at high risk of requiring healthcare services because of problems associated with locomotion. Cardiometabolic disorders, including obesity, hypertension, diabetes, and dyslipidemia, have a high prevalence worldwide. The purpose of this study was to determine the associations between LS and both body composition and cardiometabolic disorders. METHODS: The study participants were 165 healthy adult Japanese women volunteers living in rural areas. LS was defined as a score >=16 on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Height, body weight, body fat percentage, body mass index (BMI), and bone status were measured. Bone status was evaluated by quantitative ultrasound (i.e., the speed of sound [SOS] of the calcaneus) and was expressed as the percent of Young Adult Mean of the SOS (%YAM). Comorbid conditions of hypertension, hyperlipidemia, and diabetes were assessed using self report questionnaires. RESULTS: Twenty-nine participants (17.6 %) were classed as having LS. The LS group was older, shorter, and had a higher body fat percentage, a higher BMI, and lower bone status than the non-LS group. Multiple logistic regression analysis showed that participants with a BMI >=23.5 kg/m2 had a significantly higher risk for LS than those with a BMI <23.5 kg/m2 (odds ratio [OR] = 3.78, p < 0.01). Furthermore, GLFS-25 scores were higher in participants with than those without hypertension, diabetes, or obesity, and significantly increased with the number of present disorders. CONCLUSIONS: These findings suggest that BMI may be a useful screening tool for LS. Furthermore, because hypertension and diabetes were associated with LS, the prevention of these disorders accompanied by weight management may help protect against LS. PMID- 27677268 TI - Nine in 10 people are exposed to air pollution over WHO limits, warns report. PMID- 27677267 TI - Syndrome-Related Stigma in the General Social Environment as Reported by Women with Classical Congenital Adrenal Hyperplasia. AB - Stigma defined as "undesired differentness" (Goffman, 1963) and subtyped as "experienced" or "enacted," "anticipated," and "internalized" has been documented for patients with diverse chronic diseases. However, no systematic data exist on the association of stigma with somatic intersexuality. The current report concerns women with classical congenital adrenal hyperplasia (CAH), the most prevalent intersex syndrome, and provides descriptive data on CAH-related stigma as experienced in the general social environment (excluding medical settings and romantic/sexual partners) during childhood, adolescence, and adulthood. A total of 62 adult women with classical CAH [41 with the salt-wasting (SW) variant and 21 with the simple-virilizing (SV) variant] underwent a qualitative retrospective interview, which focused on the impact of CAH and its medical treatment on many aspects of women's lives. Deductive content analysis was performed on the transcribed texts. The women's accounts of CAH-related stigma were identified and excerpted as vignettes, and the vignettes categorized according to social context, stigma type, and the associated features of the CAH condition. Nearly two-thirds of women with either variant of CAH provided stigma vignettes. The vignettes included all three stigma types, and most involved some somatic or behavioral feature related to sex or gender. Stigma situations were reported for all ages and all social contexts of everyday life: family, peers, colleagues at work, strangers, and the media. We conclude that there is a need for systematic documentation of stigma in intersexuality as a basis for the development of improved approaches to prevention and intervention. PMID- 27677266 TI - Exploring clinicians' attitudes about using aspirin for risk reduction in people with Lynch Syndrome with no personal diagnosis of colorectal cancer. AB - Recent research has shown that aspirin reduces the risk of cancers associated with Lynch Syndrome. However, uncertainty exists around the optimal dosage, treatment duration and whether the benefits of aspirin as a risk-reducing medication (RRM) outweigh adverse medication related side-effects. Little is known about clinicians' attitudes, current practice, and perceived barriers to recommending aspirin as a RRM. To explore the attitudes of clinicians who discuss risk management options with patients with Lynch Syndrome towards using aspirin as a RRM. Clinicians were invited through professional organisations to complete an online survey. Topics included their clinical experience with Lynch Syndrome, views and practice of recommending aspirin as a RRM, and knowledge about clinical risk management guidelines for Lynch Syndrome. Comparison of attitudes was made between three professional groups. 181 respondents were included in the analysis: 59 genetics professionals (genetic counsellors and clinical geneticists, medical oncologists with specialist training in familial cancer), 49 gastroenterologists and 73 colorectal surgeons. Most clinicians (76 %) considered aspirin to be an effective RRM and most (72 %) were confident about discussing it. In all professional categories, those who were confident about discussing aspirin with patients perceived it to be an effective RRM (OR = 2.8 [95 % CI = 1.8-4.2], p < 0.001). Eighty percent (47/59) of genetics professionals reported having discussed the use of aspirin with Lynch Syndrome patients compared to 69 % of gastroenterologists and 68 % of colorectal surgeons. Those who considered aspirin as an effective RRM or who felt confident in their knowledge of the aspirin literature were more likely (OR = 10 [95 % CI = 1.5-65], p = 0.010, OR = 6 [95 % CI = 2.2-16], p < 0.001, respectively) to discuss it with their patients than other professionals in the study. Similarly health professionals who felt confident in their knowledge of literature of aspirin/confident in discussing with the patients were more likely (OR = 6 [95 % CI = 2.2-16], p < 0.001) to discuss with their patients. Health professionals who saw more than ten patients with Lynch Syndrome per year were more likely to be confident in their knowledge of the aspirin literature and discussing it with patients (OR = 4.1 [95 % CI = 1.6-10.2], p = 0.003). Explicit recommendations to take aspirin, was reported by 65/83 (78 %) of health professionals. Eighty-seven percent of health professionals reported a need for patient educational materials about aspirin. Continuing training is needed to increase clinicians' confidence in their knowledge of the literature on the use of aspirin as a RRM. Patient education materials may be helpful in improving consistency in patient care and facilitate communication between clinicians and people living with Lynch Syndrome. PMID- 27677270 TI - Rab11, a vesicular trafficking protein, affects endoreplication through Ras mediated pathway in Drosophila melanogaster. AB - Rab11, a small monomeric GTPase associated with recycling endosomes, is a key molecule in the regulation of vesicular trafficking and is involved in the development and differentiation of many Drosophila tissues through interaction with diverse signaling pathways. In this study, we report for the first time that Rab11 affects endoreplication through a Ras-mediated pathway. Suppression of Rab11 activity in salivary glands, an endoreplicating tissue, leads to reduction in size of salivary glands with cells having a small nucleus. Endoreplication regulating proteins, CycE, E2f1 and Gem, are also down-regulated in Rab11 knocked down salivary glands suggesting that Rab11 has a role in the process of endoreplication, possibly indirectly through other pathways that regulate cell cycle progression. Ras signaling plays an important role in cell cycle progression through G/S phase transition. Ectopic expression of activated Ras in salivary glands of Rab11 down-regulated individuals rescues the small-sized glands to intermediate size. Furthermore, we observed altered localization of Ras in Rab11 down-regulated salivary glands. It is likely that the low level of endoreplication in the Rab11 down-regulated condition is Ras-mediated. PMID- 27677269 TI - Isolation, characterization and immunomodulatory-associated gene transcription of Wharton's jelly-derived multipotent mesenchymal stromal cells at different trimesters of cow pregnancy. AB - The possibility of isolating bovine mesenchymal multipotent stromal cells (MSCs) from fetal adnexa is an interesting prospect due to the potential use of these cells in biotechnological applications. However, little is known about the properties of these progenitor cells in bovine species. Wharton's jelly (WJ) MSC cells were obtained from the umbilical cord of bovine fetuses at three different stages of pregnancy and divided into groups 1, 2 and 3 according to gestational trimester. Cell morphology, from the three stages of pregnancy, typically appeared fibroblast-like spindle-shaped, presenting the same viability and number. Moreover, the proliferative ability of T-cells in response to a mitogenic stimulus was suppressed when WJMSC cells were added to the culture. Multilineage properties were confirmed by their ability to undergo adipogenic, osteogenic/chondrogenic and neurogenic differentiation. Mesenchymal phenotyping, CD105+, CD29+, CD73+ and CD90+ cell markers were detected in all three cell groups, yet these markers were considered more expressed in MSCs of group 2 (p < 0.005). Expression of cytokines IL2, IL6RR, INFAC, INFB1, IFNG, TNF and LTBR were downregulated, whereas IL1F10 expression was upregulated in all tested WJMSCs. The present study demonstrated that WJMSCs harvested from the bovine umbilical cord at different gestational stages showed proliferative capacity, immune privilege and stemness potential. PMID- 27677272 TI - A Review of Outcomes for Colorectal Adenomas. AB - Objectives: Using data from former reports, this study reviews and analyzes the outcomes of tumor recurrence, tumor progression, and tumor-specific survival of patients with colorectal adenomas. Methods: Data were collected from 32 longitudinal studies of outcomes after the first diagnosis of colorectal adenoma and collected as individual patient results, that is, as failure times from the first tumor to the three outcomes. Altogether, there were 45,286 patients, including 22,148 for the outcome of additional adenomas, 23,796 for the outcome of progression to invasive carcinoma, and 2,602 for the outcome of disease specific survival (some patients were available for more than one outcome). Results: In these data, the mean time to additional adenomas was 6 years, the mean time to invasive carcinoma was 15.9 years, and the mean tumor-specific survival time was 21.9 years. Conclusions: Although greater than 50% of those with colorectal adenomas will have additional adenomas, few progress to invasive tumor or die of colorectal cancer. PMID- 27677273 TI - Simultaneous Determination of Cytochrome P450 Oxidation Capacity in Humans: A Review on the Phenotyping Cocktail Approach. AB - Intra- and/or inter-individual variability in drug response is mainly a result of either subtherapeutic or supratherapeutic plasma levels of the active drugs and their metabolites, with this variability mainly being influenced by differences in the rate of drug metabolism. Indeed, drug metabolism is largely determined by genetic polymorphism in the CYP enzymes, which are responsible for approximately 85% of the drug metabolism process. However, this genetic heterogeneity can accurately predict actual drug metabolizing capacity (oxidation phenotype) for some individuals: poor metabolizers (PMs), who cannot produce the drug metabolizing enzymes, and 20% of ultra-rapid metabolizers. According to EMA recommendations, phenotyping procedures for drug interaction studies and clinical research are therefore required to obtain actual data on the main CYP enzymes. With this purpose, cocktail phenotyping approaches give information on the activity of different CYPs in just one experiment. In this review, the issues related to the phenotyping of the main CYP enzymes are reviewed, and the current in vivo phenotyping cocktails are analysed: the sampling procedures, probe drugs utilized, analytical techniques and main applications are also discussed. Based on this analysis, a fully validated cocktail approach to measure the metabolic activity of the main CYP enzymes and drug transporters is still required. This novel approach should fulfil certain conditions: a faster and simpler analytical methodology to obtain information on several CYPs in one experiment, minimal sample amounts, and minimal doses of optimal probe drugs. PMID- 27677271 TI - Ultrastructural and immunocytochemical evidence for the reorganisation of the milk fat globule membrane after secretion. AB - This paper reports a detailed ultrastructural and immunocytochemical investigation of the structure of the milk fat globule membrane (MFGM) in a variety of species. The process follows the same pattern in all mammals so far investigated. The initial (or primary) MFGM immediately on release from the mammary cell is a continuous unit membrane with a thin underlying layer of cytoplasmic origin and a monolayer of phospholipid separating it from the core lipid. This structure changes rapidly as the milk fat globule (MFG) moves into the alveolar lumen. The unit membrane plus the underlying layer of cytoplasm modifies drastically into discontinuous patches and networks. These are superimposed upon a continuous apparently structureless sheet of electron dense material stabilising the MFG and similar to that which bounded the lipid in the cell. The underlying layer of the patches increases in electron density and immunocytochemistry demonstrates localisation of MFGM proteins in this layer. In four species, the dense material shows ordered paracrystalline molecular arrays in section and en face views. All the arrays show the same basic pattern and unit size as determined by optical diffraction. Similar patches, networks and arrays are present on the surface of expressed MFG. Negative staining of lipid-extracted expressed MFGs shows similar patches and networks of membrane. These also occasionally show the crystalline arrays and label with MFGM protein antibodies. Similar networks and strands of plasma membrane on the MFG surface are shown by our CLSM examination of unfixed expressed MFG from mice genetically modified to express a fluorescent molecule as a normal plasma membrane constituent. PMID- 27677274 TI - Impact of genetic variation and long-term limited water availability on the ecophysiology of young Sitka spruce (Picea sitchensis (Bong.) Carr.). AB - Future limited water availability may reduce the potential of tree improvement to increase timber yields. We investigated ecophysiological variation between full sibling families of Sitka spruce (Picea sitchensis (Bong.) Carr.) growing under contrasting water availability conditions: control (optimal) water availability and limited water availability. One-year-old seedlings of nine improved families plus an unimproved seed lot were grown in pots in a greenhouse and the two water availability treatments imposed via drip irrigation. Whole-plant water use varied between families. Stomatal conductance and the light-saturated quantum yield of photosystem II at times differed between families, but not consistently. Certain families showed considerably greater increases in electron transport rate with increasing photosynthetically active radiation. Limited water availability resulted in reduced branch water potential, leaf stomatal conductance and transpiration per unit leaf area, and increased whole-plant water-use efficiency, in all genetic material. The responses of plant water use and leaf carbon isotope composition to water limitation, were, however, initially influenced by variation in vigour between families-with conservative growth in some material slowing the decline in substrate moisture content. As the duration of water deficit extended, these variables showed a more uniform response across families. Between-family variation in physiological mechanisms of drought tolerance was not detected. Thus, for Sitka spruce, assessing juvenile material may not allow selection to prevent reductions in productivity associated with long-term sub-optimal growing conditions, but screening for conservative growth (within families as well as between families) may be beneficial where survival of relatively short-term water limitation is the primary concern. PMID- 27677275 TI - Human-Animal Interface: The Case for Influenza Interspecies Transmission. AB - Since the 1990s, the threat of influenza viruses to veterinary and human public health has increased. This coincides with the larger global populations of poultry, pigs, and people and with changing ecological factors. These factors include the redistribution of the human population to cities, rapid mass transportation of people and infectious agents, increased global land use, climate change, and possible changes in viral ecology that perpetuate highly pathogenic influenza viruses in the aquatic bird reservoir. The emergence of H5N1, H7N9, and H9N2 subtypes of influenza A virus and the increased genetic exchange among influenza viruses in wild aquatic birds, domestic poultry, swine, and humans pose a continuing threat to humanity. Here we consider the fundamental and practical knowledge of influenza A viruses at the human-animal interfaces to facilitate the development of novel control strategies and modified agricultural practices that will reduce or prevent interspecies transmission. PMID- 27677276 TI - Factors Affecting Outcome of Tuberculosis in Children in Italy: An Ecological Study. AB - INTRODUCTION: Tuberculosis is a major problem in children depending on their families for management and a re-emerging disease in low incidence countries, where foreign-born cases account for a large proportion of cases. METHODS: We investigated socioeconomic features of families and their impact on management and outcome of children with tuberculosis disease seen at a tertiary care centre for paediatric infectious diseases in Italy. RESULTS: Forty-nine Italian and 30 foreign-origin children were included. Children from foreign families had more complicated diseases (20 % vs 0 %; P = 0.002), harbored more drug resistant strains (20 % vs 2 %; P = 0.011), showed longer hospital stay (12 +/- 13.1 vs 5.1 +/- 6.5 days; P = 0.012) and higher proportion of missed medical visits (15.7 +/- 16 vs 8.6 +/- 9.6; P <= 0.042) than those from Italian families. Harboring drug resistant strains was an independent risk factor for complicated disease course (OR: 72.98; 95 %CI: 1.54-3468.58; P = 0.029), and this risk is higher in children from Eastern Europe (OR: 10.16; 95 %CI: 1.7-61.9; P = 0.012). CONCLUSIONS: Children from immigrant families showed an increased risk of complicated course of tuberculosis due to a higher rate of resistant strains and raise problems in clinical management. Specific protocols are needed to support these populations ensuring easy access to health services and monitoring. PMID- 27677277 TI - Hyaluronidase and Chondroitinase. AB - Glycosaminoglycans (GAGs) are important constituents of the extracellular matrix that make significant contributions to biological processes and have been implicated in a wide variety of diseases. GAG-degrading enzymes with different activities have been found in various animals and microorganisms, and they play an irreplaceable role in the structure and function studies of GAGs. As two kind of important GAG-degrading enzymes, hyaluronidase (HAase) and chondroitinase (CSase) have been widely studied and increasing evidence has shown that, in most cases, their substrate specificities overlap and thus the "HAase" or "CSase" terms may be improper or even misnomers. Different from previous reviews, this article combines HAase and CSase together to discuss the traditional classification, substrate specificity, degradation pattern, new resources and naming of these enzymes. PMID- 27677278 TI - Comparison of BACTECTM blood culture media for the detection of fungemia. AB - The aim of the present study was to investigate whether addition of the BACTECTM Mycosis bottle to the standard BACTECTM aerobic and anaerobic bottles contributed to a higher detection rate and a faster time to detection (TTD) of fungi. This was a retrospective cohort study of all patients with a positive blood culture with Candida species delivered to the Department of Clinical Microbiology, Herlev and Gentofte Hospital, Denmark in the 8-year period 2006 through 2014. The patients had at least one BACTECTM aerobic and one Mycosis bottle sampled at the same time and at least one of the bottles yielded growth of fungi. Among 184 patients included, 173 were examined using BACTECTM aerobic, anaerobic and Mycosis bottles. The anaerobic vial generally had the lowest detection rate and the longest TTD. The detection rate of BACTECTM aerobic plus anaerobic with the BACTECTM Mycosis bottle was significantly higher than the detection rate of BACTECTM aerobic plus anaerobic without BACTECTM Mycosis bottle for all species after 1-5 days, and specially for Candida glabrata at 2, 3, 4 and 5 days. TTD for C. glabrata was significantly shorter for BACTECTM Mycosis than TTD for BACTECTM aerobic or anaerobic bottles after 1/2 to 4 days. When combining "first or only" detection, the BACTECTM Mycosis bottle had a significantly higher detection as compared to the aerobic bottle. Addition of the BACTECTM Mycosis bottle to the standard BACTECTM aerobic and anaerobic bottles significantly contributed to a higher detection rate and a faster TTD of fungemia. PMID- 27677279 TI - Clinical outcomes and treatment approach for community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections in Israel. AB - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasingly documented worldwide. We recently identified two major CA-MRSA clones in Israel: USA300 and t991. Here, we assessed clinical outcomes by CA-MRSA clones and the physicians' treatment approach to CA-MRSA infections. All community-onset, clinical MRSA isolates detected during 2011-2013 by Maccabi Healthcare Services were collected and characterized phenotypically and genotypically; data were collected retrospectively from electronic medical records. Of 309 patients with MRSA infections, 64 were identified as CA-MRSA (21 %). Of the CA-MRSA infections, 72 % had skin and soft tissue infections (SSTIs), 38 % were Panton-Valentine leukocidin (PVL)+, the major clone being USA300 (n = 13, 54 %). Of PVL- isolates (n = 40, 62 %), t991 was the major clone. Age was the only predictor for PVL+ CA-MRSA infection (p < 0.001). Patients with PVL+ CA-MRSA had higher incidence of SSTI recurrences (1.061 vs. 0.647 events per patient/per year, p < 0.0001) and were more likely to have the SSTI drained (64 % vs. 21 %, p = 0.003) when compared to PVL- CA-MRSA. USA300 was more common among adults, while t991 was more common among children (p = 0.002). The physician's referral to culture results and susceptibility were the only predictors of appropriate antibiotic therapy (p < 0.001). However, only a minority of physicians referred to culture results, regardless of subspecialties. PVL+ CA-MRSA isolates caused significantly more recurrences of SSTIs and increased the need for drainage compared with PVL- isolates. Physicians' awareness of CA-MRSA as a cause of SSTIs in the community was suboptimal. Culturing of pus-producing SSTIs is crucial for providing adequate antimicrobials and elucidating MRSA epidemiology. PMID- 27677280 TI - In vitro activity of tedizolid against Staphylococcus aureus and Streptococcus pneumoniae collected in 2013 and 2014 from sites in Latin American countries, Australia, New Zealand, and China. AB - Tedizolid is an oxazolidinone with an antimicrobial in vitro potency advantage against Gram-positive bacterial pathogens compared to other currently marketed drugs in this class, including linezolid. Tedizolid was compared to linezolid when tested against Staphylococcus aureus and Streptococcus pneumoniae isolates collected from countries in Latin America and the Asia-Pacific. Isolates were tested by broth microdilution susceptibility methods against tedizolid, linezolid, and non-class comparators in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The activity of tedizolid against S. aureus was potent and consistent in Latin America (MIC90, 0.5 mg/L), Australia and New Zealand (MIC90, 0.25 mg/L), and China (MIC90, 0.5 mg/L). Based on MIC90 results, tedizolid was four- to eight-fold more active than linezolid against S. aureus, including both methicillin-susceptible and -resistant isolates. Only two tedizolid non-susceptible strains were observed; both had intermediate minimum inhibitory concentration (MIC) values of 1 mg/L, for which the MICs of linezolid was higher (>=2 mg/L). Tedizolid (MIC90, 0.25 mg/L) was four-fold more potent than linezolid (MIC90, 1 mg/L) against S. pneumoniae in all countries that provided isolates. The findings from this study support the global clinical development of tedizolid for Gram-positive infections. PMID- 27677283 TI - Neonatal complications in vacuum-assisted vaginal delivery: are they associated with number of pulls, cup detachments, and duration of vacuum application? AB - PURPOSE: To explore whether the characteristics of vacuum delivery are associated with the occurrence of head injury and neonatal complications. METHODS: Retrospectively cohort study of vacuum-assisted attempted vaginal deliveries of singletons. We studied the association of total duration of vacuum application and number of pulls and cup dislodgement with (1) primary outcome: the occurrence of major (subgaleal hemorrhage, skull fracture, and intracranial hemorrhage) or minor (cephalohematoma, scalp laceration more extensive than simple abrasions) neonatal head injuries and (2) secondary outcome: the occurrence of neonatal complications, including 5-min Apgar score <7, umbilical artery pH < 7.10, shoulder dystocia, or need for neonatal intensive care unit admission. Logistic regression analysis was used to control for confounders. RESULTS: Vacuum-assisted delivery was attempted in 555 women. It was successful in 515 cases, and it failed in 40 (7.2 %). Head injury occurred in 32 (6.2 %) of vaginally delivered neonates, and it was related to duration of vacuum application (P = 0.004) and birth weight (P = 0.048). However, the associations lost a statistical significance at the multivariate analysis. Neonatal complications occurred in 25 cases (5 %), and they were associated with meconium-stained amniotic fluid (P < 0.001) and duration of vacuum application (P = 0.03) at the multivariate analysis. However, most of the complications were actually associated with the need for vacuum delivery rather than the procedure itself. CONCLUSION: Neonatal head injury after vacuum application is not independently related to total duration of vacuum application, number of pulls, or cup dislodgements. PMID- 27677281 TI - Acute otitis media with spontaneous tympanic membrane perforation. AB - The principal aim of this review is to present the current knowledge regarding acute otitis media (AOM) with spontaneous tympanic membrane perforation (STMP) and to address the question of whether AOM with STMP is a disease with specific characteristics or a severe case of AOM. PubMed was used to search for all studies published over the past 15 years using the key words "acute otitis media" and "othorrea" or "spontaneous tympanic membrane perforation". More than 250 articles were found, but only those published in English and providing data on aspects related to perforation of infectious origin were considered. Early Streptococcus pneumoniae infection due to invasive pneumococcal strains, in addition to coinfections and biofilm production due mainly to non-typeable Haemophilus influenzae, seem to be precursors of STMP. However, it is unclear why some children have several STMP episodes during the first years of life that resolve without complications in adulthood, whereas other children develop chronic suppurative otitis media. Although specific aetiological agents appear to be associated with an increased risk of AOM with STMP, further studies are needed to determine whether AOM with STMP is a distinct disease with specific aetiological, clinical and prognostic characteristics or a more severe case of AOM than the cases that occur without STMP. Finally, it is important to identify preventive methods that are useful not only in otitis-prone children with uncomplicated AOM, but also in children with recurrent AOM and those who experience several episodes with STMP. PMID- 27677282 TI - At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries. AB - AIMS: Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP. Here we investigated cross-talk between hemichannels and Ca2+/purinergic signalling in controlling blood vessel contraction. We hypothesized that hemichannel Ca2+ entry and ATP release contributes to smooth muscle cell (SMC) Ca2+ dynamics, thereby influencing vessel contractility. We applied several peptide modulators of hemichannel function and inhibitors of Ca2+ and ATP signalling to investigate their influence on SMC Ca2+ dynamics and vessel contractility. METHODS AND RESULTS: Confocal Ca2+ imaging studies on small mesenteric arteries (SMAs) from rat demonstrated that norepinephrine-induced SMC Ca2+ oscillations were inhibited by blocking IP3 receptors with xestospongin-C and by interfering with hemichannel function, most notably by the specific Cx43 hemichannel blocking peptide TAT-L2 and by TAT-CT9 that promotes Cx43 hemichannel opening. Evidence for hemichannel involvement in SMC function was supported by the fact that TAT-CT9 significantly increased SMC resting cytoplasmic Ca2+ concentration, indicating it facilitated Ca2+ entry, and by the observation that norepinephrine-triggered vessel ATP release was blocked by TAT-L2. Myograph tension measurements on isolated SMAs showed significant inhibition of norepinephrine-triggered contractility by the ATP receptor antagonist suramin, but the strongest effect was observed with TAT-L2 that gave ~80% inhibition at 37 degrees C. TAT-L2 inhibition of vessel contraction was significantly reduced in conditional Cx43 knockout animals, indicating the effect was Cx43 hemichannel-dependent. Computational modelling suggested these results could be explained by the opening of a single hemichannel per SMC. CONCLUSIONS: These results indicate that Cx43 hemichannels contribute to SMC Ca2+ dynamics and contractility, by facilitating Ca2+ entry, ATP release, and purinergic signalling. PMID- 27677284 TI - Percutaneous Hepaticojejunostomy Using a Radiofrequency Wire for Management of a Postoperative Bile Leak. AB - Postoperative biliary complications following extensive hepatic resections are complex, often requiring a multidisciplinary team approach. We describe a case of a free bile duct leak following extended right hepatectomy and surgical hepaticojejunostomy treated with percutaneous transhepatic hepaticojejunostomy in which a radiofrequency guidewire was used to gain enteral access. A modified internal/external biliary catheter was left in place. The patient was enrolled in a benign biliary stricture protocol, and 8 months later, the catheter was removed following a normal cholangiogram and biliary manometric perfusion testing. At 3 month follow-up after catheter removal, the patient is asymptomatic with no clinical, biochemical, or radiographic evidence of biliary leak or obstruction. PMID- 27677285 TI - [Clinical aspects and diagnostics of cerebral vasculitis]. AB - CLINICAL/METHODICAL ISSUE: Vasculitis is a rare cause of diseases of the central nervous system (CNS). Vasculitis can be divided into primary and secondary forms, of which the vast majority can be manifested in various organ systems, including the CNS. Isolated vasculitis of the CNS is limited to the CNS and clinical neurological symptoms as with the other forms of vasculitis, are headaches, encephalopathy, focal deficits and seizures. A criterion of isolated CNS vasculitis is the clinical and laboratory diagnostic exclusion of other forms of vasculitis and the involvement of other organ systems. STANDARD RADIOLOGICAL METHODS: Multiple leaps in the caliber of intracranial arteries in cerebral angiography and multiple, small contrast medium-enhanced lesions in magnetic resonance imaging (MRI) of the brain are typical findings, which, however, can also be found in other forms of vasculitis. PERFORMANCE: The only way of proving meningitis is by a biopsy of the brain meninges and parenchyma. It is necessary to make as accurate a diagnosis as possible, especially in the context of therapeutic options of immunosuppression with steroids and cyclophosphamide. ACHIEVEMENTS: Cerebral vasculitis is a rare entity but it is an important diagnosis to consider when the appropriate clinical symptoms are present. Thorough laboratory diagnostics and subsequent brain biopsy are necessary to confirm the diagnosis in order to then be able to initiate a specific treatment. PMID- 27677286 TI - Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells. AB - Renal cell carcinoma (RCC) accounts for 3 % of all adult malignancies and is the most lethal urological cancer. Livin is a member of the inhibitor of apoptosis protein (IAP) family, which is associated with tumor resistance to radiotherapy and chemotherapy. Clinical data also showed that patients with high tumor grades and stages have higher expression levels of Livin in RCC cells. Autophagy is a survival mechanism activated in response to nutrient deprivation. A possible role of Livin in the autophagy of RCC cells has not been investigated; therefore, this pioneer study was carried out. Livin was silenced in RCC cells (slow virus infection [SVI]-shLivin cells) by lentiviral transfection. Then, mRNA and protein expression levels in the transfected cells were assessed by quantitative fluorescence PCR and Western blotting, respectively. In addition, acridine orange staining and electron microscopy were used to assess autophagy in SVI-shLivin cells. The cisplatin IC50 values for RCC cells were measured by the CCK8 assay. Potent antitumor activities were observed in xenograft mouse models generated with Livin-silenced RCC cells in terms of delayed tumor onset and suppressed tumor growth. These results suggested that Livin silencing could increase the chemotherapeutic sensitivity of RCC cells to cisplatin and induce autophagic cell death. A possible mechanism of Bcl-2 and Akt pathway involvement was discussed specifically in this study. Overall, Livin silencing induces apoptotic and autophagic cell death and increases chemotherapeutic sensitivity of RCC cells to cisplatin. PMID- 27677287 TI - Numb/Notch signaling pathway modulation enhances human pancreatic cancer cell radiosensitivity. AB - The present study aims to evaluate whether repression of the Numb/Notch signaling pathway affects the radiosensitivity of human pancreatic cancer cell lines. Different doses of X-rays (0, 2, 3, 4, and 5 Gy) were applied to the PANC-1, SW1990, and MIA PaCa-2 human pancreatic cancer cell lines, and the Numb/Notch pathway inhibitor DAPT was added at different doses (0, 1, 3, and 5 MUmol/l). MTT assay, colony formation assay, flow cytometry, scratch assay, and Transwell experiments were performed, and qRT-PCR and Western blot were conducted for the detection of Numb expression. Tumorigenicity assay in nude mice was carried out to verify the influence of blocker of the Numb/Notch signaling pathway on the radiosensitivity of xenograft tumors. The MTT assay, colony formation assay and flow cytometry experiments revealed that proliferation decreased as radiation dose increased. The viability of PANC-1 cells at 5 Gy, SW 1990 cells at 4 Gy and 5 Gy, and MIA PaCa-2 cells at 2-5 Gy was significantly lower than that of non irradiated cells (all P < 0.05). The migration and invasion assays indicated that the PANC-1 cell line was least radiosensitive, while the MIA PaCa-2 cell line was the most radiosensitive. Numb expression significantly increased with increasing radiation dose, whereas the expression of Hes1, Notch1, and Hes5 significantly decreased compared to non-irradiated cells (P < 0.05). Compared to untreated control cells, DAPT dose dependently increased Numb expression and inhibited Notch1, Hes1, and Hes5 expressions at 2 Gy (P < 0.05). Subcutaneous tumorigenicity assay in nude mice demonstrated that DAPT increased the radiosensitivity of PANC-1, SW 1990, and MIA PaCa-2 cells. These findings suggest that Numb/Notch signaling in pancreatic cancer cells is associated with X-ray radiation and that inhibition of the Numb/Notch signaling pathway can enhance radiosensitivity, suggesting that inhibition of the Numb/Notch signaling pathway may serve as a potential target for clinical improvement of the radiosensitivity of pancreatic cancer. PMID- 27677288 TI - Overexpression of CASS4 promotes invasion in non-small cell lung cancer by activating the AKT signaling pathway and inhibiting E-cadherin expression. AB - The role of Crk-associated substrate (CAS) family members in regulating invasion and metastasis has been described in several cancers. As the fourth member of the CAS family, CASS4 is also related with positive lymph node metastasis and poor prognosis in lung cancer. However, the underlying mechanisms and downstream effectors of CASS4 in the development and progression of non-small cell lung cancer (NSCLC) remain unclear. In this study, CASS4 overexpression inhibited E cadherin expression and enhanced invasion in NSCLC cell line transfected with CASS4 plasmid, while CASS4 depletion upregulated E-cadherin expression and inhibited invasion in NSCLC cell line transfected with CASS4 siRNA. The effect of CASS4 overexpression in facilitating invasion of NSCLC cells was reversed by restoring E-cadherin expression, which indicates that CASS4 may promote invasion by inhibiting E-cadherin expression. Subsequent immunohistochemistry results confirmed that CASS4 overexpression correlated with loss of E-cadherin expression. We next investigated the phosphorylation levels of focal adhesion kinase (FAK), p38, extracellular signal-related kinase (ERK), and AKT after CASS4 plasmid or CASS4 siRNA transfection. CASS4 facilitated AKT (Ser473) phosphorylation. Treatment with an AKT phosphorylation inhibitor reversed the increased invasive capacity and downregulation of E-cadherin protein induced by CASS4 overexpression. Taken together, the present results indicate that CASS4 may promote NSCLC invasion by activating the AKT signaling pathway, thereby inhibiting E-cadherin expression. PMID- 27677289 TI - Arsenic trioxide inhibits lung metastasis of mouse colon cancer via reducing the infiltration of regulatory T cells. AB - The purpose of this study was to investigate the effects of arsenic trioxide (As2O3) on the infiltration of regulatory T cells (Tregs) in the local lung metastasis of mouse colon cancer in vivo and the regulation of Tregs in cytokine induced killer cells (CIKs) in vitro. A high Tregs infiltration mouse colon cancer lung metastasis model was established by intravenous injection of CT26 murine colon carcinoma cells. Tumor-bearing mice were randomly divided into three groups: control group, low-dose As2O3 group, and high-dose As2O3 group. For in vitro studies, CIKs were treated with vehicle control or 0.1, 1, or 5 MUM As2O3. The level of Tregs was detected via flow cytometry, Foxp3 expression was assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT PCR), the level of interferon gamma (IFN-gamma) was evaluated by enzyme-linked immunoassay (ELISA), and the cytotoxic activity of As2O3-treated CIKs was assessed through a lactate dehydrogenase (LDH) release assay. Obvious lung metastasis was observed 3 days after CT26 murine colon carcinoma cell injection. The numbers of Tregs in the lungs and spleens of tumor-bearing mice were significantly higher than those of the normal group (p < 0.01). As2O3 treatment increased the mouse weight as well as reduced the number of metastatic lung nodules and the lung/body weight ratio (p < 0.01). Moreover, As2O3 treatment significantly reduced the Tregs proportion and the Foxp3 messenger RNA (mRNA) levels in metastatic lung tissues (p < 0.01). In vitro, As2O3 significantly reduced the Tregs proportion and the Foxp3 mRNA levels (p < 0.01) and significantly increased the cytotoxic activity of CIKs and the IFN-gamma levels in the supernatant of cultured CIKs (p < 0.01). As2O3 might inhibit lung metastasis of colon cancer by reducing the local infiltration of Tregs and increase the cytotoxic activity of CIKs by suppressing Tregs. PMID- 27677290 TI - Are PEEK-on-Ceramic Bearings an Option for Total Disc Arthroplasty? An In Vitro Tribology Study. AB - BACKGROUND: Most contemporary total disc replacements (TDRs) use conventional orthopaedic bearing couples such as ultrahigh-molecular-weight polyethylene (polyethylene) and cobalt-chromium (CoCr). Cervical total disc replacements incorporating polyetheretherketone (PEEK) bearings (specifically PEEK-on-PEEK bearings) have been previously investigated, but little is known about PEEK-on ceramic bearings for TDR. QUESTIONS/PURPOSES: (1) What is the tribologic behavior of a PEEK-on-ceramic bearing for cervical TDR under idealized, clean wear test conditions? (2) How does the PEEK-on-ceramic design perform under impingement conditions? (3) How is the PEEK-on-ceramic bearing affected by abrasive wear? (4) Is the particle morphology from PEEK-on-ceramic bearings for TDRs affected by adverse wear scenarios? METHODS: PEEK-on-ceramic cervical TDR bearings were subjected to a 10 million cycle ideal wear test based on ASTM F2423 and ISO 181912-1 using a six-station spine wear simulator (MTS, Eden Prairie, MN, USA) with 5 g/L bovine serum concentration at 23 degrees +/- 2 degrees C (ambient temperature). Validated 1 million cycle impingement and 5 million cycle abrasive tests were conducted on the PEEK-on-ceramic bearings based, in part, on retrieval analysis of a comparable bearing design as well as finite element analyses. The ceramic-on-PEEK couple was characterized for damage modes, mass and volume loss, and penetration and the lubricant was subjected to particle analysis. The resulting mass wear rate, volumetric wear rate, based on material density, and particle analysis were compared with clinically available cervical disc bearing couples. RESULTS: The three modes of wear (idealized, impingement, and abrasive) resulted in mean mass wear rates of 0.9 +/- 0.2 mg/MC, 1.9 +/- 0.5 mg/MC, and 2.8 +/- 0.6 mg/MC, respectively. The mass wear rates were converted to volumetric wear rates using density and found to be 0.7 +/- 0.1 mm3/MC, 1.5 +/- 0.4 mm3/MC, and 2.1 +/- 0.5 mm3/MC, respectively. During each test, the PEEK endplates were the primary sources of wear and demonstrated an abrasive wear mechanism. Under idealized and impingement conditions, the ceramic core also demonstrated slight polishing of the articulating surface but the change in mass was unmeasurable. During abrasive testing, the titanium transfer on the core was shown to polish over 5 MC of testing. In all cases and consistent with previous studies of other PEEK bearing couples, the particle size was primarily < 2 um and morphology was smooth and spheroidal. CONCLUSIONS: Overall, the idealized PEEK-on-ceramic wear rate (0.7 +/- 0.1 mm3/MC) appears comparable to the published wear rates for other polymer-on-hard bearing couples (0.3-6.7 mm3/MC) and within the range of 0.2 to 1.9 mm3/MC reported for PEEK-on-PEEK cervical disc designs. The particles, based on size and morphology, also suggest the wear mechanism is comparable between the PEEK-on-ceramic couple and other polymer-on-ceramic orthopaedic couples. CLINICAL RELEVANCE: The PEEK-on-ceramic bearing considered in this study is a novel bearing couple for use in total disc arthroplasty devices and will require clinical evaluation to fully assess the bearing couple and total disc design. However, the wear rates under idealized and adverse conditions, and particle size and morphology, suggest that PEEK-on-ceramic bearings may be a reasonable alternative to polyethylene-on-CoCr and metal-on-metal bearings currently used in cervical TDRs. PMID- 27677291 TI - Phylogenetic Analysis of Molluscan Metallothioneins: Evolutionary Insight from Crassostrea virginica. AB - Mechanisms by which organisms genetically adapt to environmental conditions are of fundamental importance to studies of evolutionary biology and environmental physiology. Natural selection acts on existing genetic variation leading to adaptation through selection of new mutations that confer beneficial advantages to populations. The American oyster, Crassostrea virginica, is an excellent model to investigate interactions between environmental and ecological factors as driving forces for natural selection. A great example of this is represented by the diversity of C. virginica metallothioneins (CvMT), metal-binding proteins involved in homeostasis and tolerance, that have resulted from a series of duplication events to produce the greatest structural diversity of MT proteins found in a single species. We present phylogenetic evidence of two distinct ancestral beta-domain MTs that gave rise to a variety of betabeta and alphabeta CvMT proteins, as well as CvMT-II proteins consisting solely of one to four alpha domains. Furthermore, we annotate the complete locus containing the paralogous CvMT-I, -II, and -IV genes, providing supporting evidence of a hypothesized series of exon and gene duplication events that gave rise to the various CvMT-I and -II isoforms. We also highlight unique MT expression profiles from four separate C. virginica populations to demonstrate differences in gene diversity and copy number which appear to be enriched in southeastern U.S. oyster populations. These observations contribute to a better understanding of the molecular mechanisms leading to adaptation in organisms that experience substantial environmental stress, with a specific focus on evolutionary adaptations of gene structure. PMID- 27677292 TI - Serological, molecular detection and potential risk factors associated with camel brucellosis in Pakistan. AB - Brucellosis is one of the most important zoonoses in developing countries and was considered the most widespread zoonosis in the world. Brucellosis was reported in camels and has been reported from all camel-keeping countries.The present study was performed in three districts (Jhang, Chiniot, and Bhakkar) of Punjab province of Pakistan. A total of 200 camel (Camelus bactrianus) sera were collected using random and multistage cluster sampling from different areas. Fifty samples were collected from one organized governmental farm. One hundred fifty samples were collected randomly from nomadic/pastoral production systems. All sera were tested with Rose Bengal plate agglutination test (RBPT) and confirmed by ELISA. Genomic DNA was extracted from all serum samples and tested by real-time PCR. Various potential risk factors (season, rearing with other animals, and abortion or orchitis history) recorded through questionnaires were statistically analyzed by Chi-square test.In total, 5 % of investigated sera were positive by RBPT. Only 2 % of the camel sera were CELISA positive. Brucella abortus DNA was detected in 1.5 % of the investigated animals. Season, rearing of camels with other ruminants, abortion, and orchitis history were found to be statistically significant (p < 0.05) disease for determinants.Camel brucellosis is a zoonotic disease in the Pakistani Punjab with various risk factors maintaining and perpetuating its spread. Therefore, there is a need for implementing control measures and raising public health awareness in prevention of brucellosis in Pakistan. PMID- 27677293 TI - A Quinone-Containing Compound Enhances Camptothecin-Induced Apoptosis of Lung Cancer Through Modulating Endogenous ROS and ERK Signaling. AB - The natural compound camptothecin (CPT) derivatives have widely been used for anti-cancer treatments, including lung cancer. However, many chemoresistant cancer cells often develop a relatively higher threshold for inducing apoptosis, causing a limited efficacy of anti-cancer drugs. Likewise, lung cancer cells acquire chemoresistance against CPT analogs, such as irinotecan and topotecan, finally resulting in an unsatisfied outcome and poor prognosis of lung cancer patients. TFPP is a quinone-containing compound as a candidate for CPT-based combination chemotherapy. In this study, we examined the effect of TFPP and CPT cotreatment on non-small cell lung cancer (NSCLC) cells. Cell proliferation and flow cytometry-based Annexin-V/PI staining assays demonstrated the synergistic effect of TFPP on CPT-induced apoptosis in both NSCLC A549 and H1299 cells. The results of CPT and TFPP cotreatment cause the regulation of the ERK-Bim axis and the activation of mitochondrial-mediated caspase cascade, including caspase-9 and caspase-3. Besides, TFPP significantly enhanced CPT-induced endogenous reactive oxygen species (ROS) in the two NSCLC cells. In contrast, the treatment of N acetyl-L-cysteine (NAC), an ROS scavenger, rescues the apoptosis of NSCLC cells induced by TFPP and CPT cotreatment, suggesting that the synergistic effect of TFPP on CPT-induced anti-NSCLC cells is through upregulating ROS production. Consequently, our results suggest that TFPP sensitizes NSCLC towards CPT-based chemotherapy may act through decreasing the apoptosis-initiating threshold. Therefore, TFPP may be a promising chemosensitizer for lung cancer treatment, and the underlying mechanism warrants further. PMID- 27677294 TI - The impact of margin status determined by the one-millimeter rule on tumor recurrence and survival following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. AB - PURPOSE: The tumor-node-metastasis (TNM) classification defines R1 as the presence of tumor cells at the resection margin, while the current Royal College of Pathologists guidelines for pancreaticoduodenectomy specimens regard the presence of tumor cells within 1 mm from the resection margin as R1 (the "1-mm rule"). The aims of this study were to investigate the resection margin status of pancreatic head cancer retrospectively according to both the TNM and 1-mm rule classifications, and to evaluate the postoperative survival and tumor recurrence patterns. METHODS: A total of 117 patients with pancreatic head cancer were the subjects of this study. RESULTS: R11-mm rule resection was associated with a significantly worse disease-free survival (DFS) than R01-mm rule resection (p = 0.0259), while R1TNM had no impact on DFS. R11-mm rule resection margin status correlated with the incidence of tumor recurrence in the liver (p = 0.0483). In a multivariate analysis, R11-mm rule resection was the independent variable for predicting poor DFS (hazard ratio 1.71; p = 0.0289). CONCLUSIONS: R1 resection margin status determined by the 1-mm rule may be an independent indicator for predicting disease recurrence, especially liver metastasis. These results may be useful for selecting the appropriate adjuvant therapy protocol and conducting strict surveillance in PDAC patients. PMID- 27677295 TI - Laparoscopic versus open surgery for obese patients with rectal cancer: a retrospective cohort study. AB - PURPOSE: To evaluate the advantages of laparoscopic surgery for rectal cancer in obese patients. METHODS: We collected clinical data from consecutive patients who underwent anterior resection for rectal cancer between 2008 and 2015 to compare the surgical outcomes of a laparoscopic surgery group (LG) with those of an open surgery group (OG) stratified by obesity. Obesity was defined as a body mass index >=25. RESULTS: A total of 268 patients were analyzed, with 157 in the LG (44 obese and 113 non-obese) and 111 in the OG (25 obese and 86 non-obese). The rates of complications between the LG and the OG were 18.5 vs. 11.6 % (p = 0.18) for the non-obese patients and 18.2 vs. 20.0 % (p = 1.0) for the obese patients, respectively, without a significant difference. Operative time was longer in the LG than in the OG, but the difference between the non-obese and obese patients was not significant, being 266 vs. 189 min (p < 0.0001) and 260 vs. 254 min (p = 0.96), respectively. Blood loss was much lower in the LG for both obese and non obese patients, being 10 vs. 435 mL (p < 0.0001) and 10 vs. 275 mL (p < 0.0001), respectively. CONCLUSION: There were no significant differences between LG and OG in operative time or complications for obese patients with rectal cancer, and blood loss was much lower in the LG. Thus, laparoscopic surgery is a safe and minimally invasive approach for obese patients with rectal cancer. PMID- 27677296 TI - Diffusion tensor imaging analysis of the brain in the canine model of Krabbe disease. AB - PURPOSE: The goal of this study was to compare the diffusion tensor imaging (DTI) metrics from an end-stage canine Krabbe brain evaluated by MR imaging ex vivo to those of a normal dog brain. We hypothesized that the white matter of the canine Krabbe brain would show decreased fractional anisotropy (FA) values and increased apparent diffusion coefficient (ADC) and radial diffusivity (RD) values. METHODS: An 11-week-old Krabbe dog was euthanized after disease progression. The brain was removed and was placed in a solution of 10% formalin. MR imaging was performed and compared to the brain images of a normal dog that was similarly fixed post mortem. Both brains were scanned using similar protocols on a 7 T small-animal MRI system. For each brain, maps of ADC, FA, and RD were calculated for 11 white matter regions and five control gray-matter regions. RESULTS: Large decreases in FA values, increases in ADC values, and increases in RD (consistent with demyelination) values, were seen in white matter of the Krabbe brain but not gray matter. ADC values in gray matter of the Krabbe brain were decreased by approximately 29% but increased by approximately 3.6% in white matter of the Krabbe brain. FA values in gray matter were decreased by approximately 3.3% but decreased by approximately 29% in white matter. RD values were decreased by approximately 27.2% in gray matter but increased by approximately 20% in white matter. CONCLUSION: We found substantial abnormalities of FA, ADC, and RD values in an ex vivo canine Krabbe brain. PMID- 27677297 TI - Fish oil and wheat-germ oil supplementation restores ovarian function in streptozotocin-diabetic rats. AB - Diabetes is a chronic metabolic disorder and has a profound impact on women's reproductive health. This study aimed to investigate the protective effect of a mixture of fish oil (FO) and wheat-germ oil (WGO) on ovarian dysfunction in diabetic rats. Female Albino rats were divided into control, diabetic and FO-WGO diabetic groups. Diabetes was induced by intraperitoneal injection of 65mgkg-1 streptozotocin (STZ). Three weeks later, rats were given oral supplement of 0.4gkg-1 oil mix (1000mg FO+100mg WGO) daily for 3 weeks. Antioxidant activity was assessed by measuring malondialdehyde (MDA) and reduced glutathione (GSH) levels, the GSH:oxidised glutathione (GSSG) ratio and superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Ovary function was indicated by serum concentrations of FSH, oestradiol (E2), LH, anti-Mullerian hormone (AMH), ovary histopathology and follicle counts. Anti-inflammatory properties were detected by measuring nuclear factor (NF)-kappaB in follicular cells by immunohistochemistry. FO-WGO supplementation enhanced CAT, SOD and GPx activities and raised GSH levels and the GSH:GSSG ratio. Supplementation also increased FSH, E2, LH and AMH levels and follicle counts. Moreover, NF-kB expression and MDA were reduced. These findings indicate that FO-WGO supplementation preserved ovarian function in STZ-induced diabetic rats. PMID- 27677298 TI - Participatory methods for research prioritization in primary care: an analysis of the World Cafe approach in Ireland and the USA. AB - Background: There are increasing imperatives for patients and members of the public to engage as partners in identifying health research priorities. The use of participatory methods to engage stakeholders in health care in research prioritization is not commonly reported. Objective: This article analyses the use of World Cafes as a participatory method for research prioritization with marginalized communities in Ireland and the USA. Methods: The principles of purposeful and snowball sampling were followed in both settings and a diverse range of community and health care stakeholders participated (n = 63 Ireland and n = 55 USA). The principles for a classic World Cafe were employed but there were novel features in each setting as well. Stewart et al.'s (Patients' and clinicians' research priorities. Health Expect 2011; 14: 439-48, conceptual framework for patient engagement was adapted and used to comparatively analyse the strengths and weaknesses of the World Cafes, focusing on agenda setting, engagement with research processes, interactional features and outputs. Results: Design principles for World Cafes were found to align with high-quality patient engagement for research prioritization in both settings. They served to facilitate meaningful collaboration among stakeholder groups in research prioritization (research agenda setting) and explored research priorities (engagement with research). The cafe ambience, emphasis on hospitality and self facilitation created an environment for dialogues within and across participating groups (interactional features). There was a commitment to follow-up actions with reference to possible subsequent research (outputs). Conclusions: The World Cafe is a valuable, participatory, flexible method that can be used with community and health care stakeholders for research prioritization with marginalized communities. PMID- 27677299 TI - How can we improve crop genotypes to increase stress resilience and productivity in a future climate? A new crop screening method based on productivity and resistance to abiotic stress. AB - The need to accelerate the selection of crop genotypes that are both resistant to and productive under abiotic stress is enhanced by global warming and the increase in demand for food by a growing world population. In this paper, we propose a new method for evaluation of wheat genotypes in terms of their resilience to stress and their production capacity. The method quantifies the components of a new index related to yield under abiotic stress based on previously developed stress indices, namely the stress susceptibility index, the stress tolerance index, the mean production index, the geometric mean production index, and the tolerance index, which were created originally to evaluate drought adaptation. The method, based on a scoring scale, offers simple and easy visualization and identification of resilient, productive and/or contrasting genotypes according to grain yield. This new selection method could help breeders and researchers by defining clear and strong criteria to identify genotypes with high resilience and high productivity and provide a clear visualization of contrasts in terms of grain yield production under stress. It is also expected that this methodology will reduce the time required for first selection and the number of first-selected genotypes for further evaluation by breeders and provide a basis for appropriate comparisons of genotypes that would help reveal the biology behind high stress productivity of crops. PMID- 27677300 TI - Artificial neural network EMG classifier for functional hand grasp movements prediction. AB - Objective To design and implement an electromyography (EMG)-based controller for a hand robotic assistive device, which is able to classify the user's motion intention before the effective kinematic movement execution. Methods Multiple degrees-of-freedom hand grasp movements (i.e. pinching, grasp an object, grasping) were predicted by means of surface EMG signals, recorded from 10 bipolar EMG electrodes arranged in a circular configuration around the forearm 2 3 cm from the elbow. Two cascaded artificial neural networks were then exploited to detect the patient's motion intention from the EMG signal window starting from the electrical activity onset to movement onset (i.e. electromechanical delay). Results The proposed approach was tested on eight healthy control subjects (4 females; age range 25-26 years) and it demonstrated a mean +/- SD testing performance of 76% +/- 14% for correctly predicting healthy users' motion intention. Two post-stroke patients tested the controller and obtained 79% and 100% of correctly classified movements under testing conditions. Conclusion A task-selection controller was developed to estimate the intended movement from the EMG measured during the electromechanical delay. PMID- 27677301 TI - Specialist care in the management of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC), both chronic, relapsing, incurable conditions. Phenotypical expression may vary, and a fraction of patients respond appropriately to conventional drugs without complications or need for hospitalization. At the opposite end of this spectrum, 30-40% of patients have severe, aggressive disease poorly responsive to conventional drugs. These latter patients urgently need more advanced therapy options, which also represent additional safety concerns. IBD management has become increasingly complex, and specialist care is deemed associated with better outcomes in the management of patients with IBD. PMID- 27677302 TI - A Convenient Ultraviolet Irradiation Technique for Synthesis of Antibacterial Ag Pal Nanocomposite. AB - In the present work, palygorskite (Pal) was initially subjected to an ion exchange reaction with silver ions (Pal-Ag(+)). Subsequently, Ag-Pal nanocomposites were assembled by a convenient ultraviolet irradiation technique, using carbon dots (CDs) derived from wool fiber as the reducing agent. The obtained nanocomposites were characterized by powder X-ray diffraction (XRD), ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy. The XRD patterns and UV-vis absorption spectra confirmed the formation of the Ag nanoparticles (NPs). Meanwhile, the TEM images showed that the Ag NPs, which exhibited sizes in the range of 3-7 nm, were located on the surface of the Pal nanofiber structures. Furthermore, the antibacterial activity of the nanocomposites was evaluated against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria by applying the disc diffusion method and minimum inhibitory concentration test. Owing to their good antibacterial properties, the Ag-Pal nanocomposites are considered to be a promising bactericide with great potential applications. PMID- 27677304 TI - Tunneling-Magnetoresistance Ratio Comparison of MgO-Based Perpendicular-Magnetic Tunneling-Junction Spin Valve Between Top and Bottom Co2Fe6B2 Free Layer Structure. AB - For the perpendicular-magnetic-tunneling-junction (p-MTJ) spin valve with a nanoscale-thick bottom Co2Fe6B2 free layer ex situ annealed at 400 degrees C, which has been used as a common p-MTJ structure, the Pt atoms of the Pt buffer layer diffused into the MgO tunneling barrier. This transformed the MgO tunneling barrier from a body-centered cubic (b.c.c) crystallized layer into a mixture of b.c.c, face-centered cubic, and amorphous layers and rapidly decreased the tunneling-magnetoresistance (TMR) ratio. The p-MTJ spin valve with a nanoscale thick top Co2Fe6B2 free layer could prevent the Pt atoms diffusing into the MgO tunneling barrier during ex situ annealing at 400 degrees C because of non necessity of a Pt buffer layer, demonstrating the TMR ratio of ~143 %. PMID- 27677303 TI - Fabrication and Properties of Carbon-Encapsulated Cobalt Nanoparticles over NaCl by CVD. AB - Carbon-encapsulated cobalt (Co@C) nanoparticles, with a tunable structure, were synthesized by chemical vapor deposition using Co nanoparticles as the catalyst and supported on a water-soluble substrate (sodium chloride), which was easily removed by washing and centrifugation. The influences of growth temperature and time on the structure and magnetic properties of the Co@C nanoparticles were systematically investigated. For different growth temperatures, the magnetic Co nanoparticles were encapsulated by different types of carbon layers, including amorphous carbon layers, graphitic layers, and carbon nanofibers. This inferred a close relationship between the structure of the carbon-encapsulated metal nanoparticles and the growth temperature. At a fixed growth temperature of 400 degrees C, prolonged growth time caused an increase in thickness of the carbon layers. The magnetic characterization indicated that the magnetic properties of the obtained Co@C nanoparticles depend not only on the graphitization but also on the thickness of the encapsulated carbon layer, which were easily controlled by the growth temperatures and times. Optimization of the synthesis process allowed achieving relatively high coercivity of the synthesized Co@C nanoparticles and enhancement of its ferromagnetic properties, which make this system promising as a magnetic material, particularly for high-density magnetic recording applications. PMID- 27677305 TI - Long-Term Stability of a Portable Carbon Monoxide Single-Breath Diffusing Capacity Instrument. AB - BACKGROUND: The 2005 American Thoracic Society/European Respiratory Society guidelines for single-breath diffusing capacity of the lung for carbon monoxide (DLCO) recommend a weekly biological control test and/or DLCO simulator to detect instrument error drift. Very little has been published regarding the results of such a quality assurance program. Our aim was to analyze the long-term stability of a portable DLCO instrument. METHODS: We used a new EasyOne Pro system and checked its accuracy using a DLCO simulator with 2 reference gases (concentration A: carbon monoxide [CO] = 0.1% and helium = 6.52%; concentration B: CO = 0.08% and helium = 7.21%) during the first 3 y of use in our large clinical laboratory. To detect instrument drift, a healthy woman (MSC), age 43 y old at baseline, tested herself every week during this period of time. RESULTS: More than 6,000 spirometry and 5,000 DLCO maneuvers were done using this instrument for patients during these 3 y. There were no failures in the daily volume and flow checks or the CO and helium calibration checks performed automatically by the instrument. The differences between the simulator DLCO and the measured DLCO were -0.91 +/- 1.33 mL/min/mm Hg and -0.61 +/- 1.45 mL/min/mm Hg for concentration A and concentration B, respectively. The results of the 110 biological control tests were: mean 30.8 +/- 1.7 mL/min/mm Hg (95% CI 30.5-31.1), coefficient of variation of 5.4% in DLCO, and repeatability of 2.5 mL/min/mm Hg. Only 4 measurements were outside +/-3 mL/min/mm Hg (3.6%). Her mean alveolar volume was 4.2 +/- 0.25 L with coefficient of variation of 6.2%; her inspired volume was 3.05 +/- 0.14 L, and coefficient of variation = 4.5%. CONCLUSIONS: Measurements of DLCO were stable over the 3-y period without any need for manual recalibration of the instrument. The biological control was as good as the DLCO simulator to evaluate this kind of device in a long-term laboratory quality control program. PMID- 27677306 TI - Alternating Motion Rate to Distinguish Elderly People With History of Pneumonia. AB - BACKGROUND: Under the hypothesis that elderly people in the community may have deficient oropharyngeal dysfunction, the purpose of this case-control study was to compare oral and physical characteristics in elderly people with and without a history of pneumonia and to identify factors distinguishing them. METHODS: In 2014, we examined 1,311 elderly people who agreed to participate in a longitudinal and intervention study for the community-dwelling elderly. We looked at such physical characteristics as body composition, grip power, gait, and balance and at oropharyngeal characteristics, such as alternating motion rate (AMR) in speech and the repetitive saliva-swallowing test (RSST). The subjects were also asked about past history of pneumonia and other morbid conditions. From that information, we extracted 24 subjects reporting to have had pneumonia within the previous 5 y as well as 172 other subjects who matched the pneumonia subjects with respect to age, sex, and number of other morbidities to form 2 groups for comparisons. We also subjected the data to a logistic regression analysis, with having or not having pneumonia as the dependent variable, oral and physical characteristics as independent variables, and age and sex as covariates. RESULTS: No significant differences were seen in physical characteristics between the 2 groups. Among the oropharyngeal characteristics, AMR was significantly lower in the pneumonia subjects (P = .005, effect size = 0.20), whereas RSST exhibited no significant difference between the 2 groups. Logistic regression revealed AMR to be the only factor related to pneumonia (P = .002, odds ratio 0.169, 95% CI 0.056 0.508). CONCLUSIONS: In community-dwelling elderly people, association of pneumonia with skilled tongue control (AMR) rather than with swallowing (RSST) prompts a reexamination of what constitutes being at risk for pneumonia. PMID- 27677307 TI - Infection levels of the eyeworm Oxyspirura petrowi and caecal worm Aulonocephalus pennula in the northern bobwhite and scaled quail from the Rolling Plains of Texas. AB - Northern bobwhite (Colinus virginianus) and scaled quail (Callipepla squamata) have experienced chronic declines within the Rolling Plains ecoregion of Texas. Parasitic infection, which has long been dismissed as a problem in quail, has not been studied thoroughly until recently. A total of 219 northern bobwhite and 101 scaled quail from Mitchell County, Texas were captured and donated from 2014 to 2015, and examined for eyeworm (Oxyspirura petrowi) and caecal worm (Aulonocephalus pennula) infections. In 2014, bobwhites averaged 19.6 +/- 1.8 eyeworms and 98.6 +/- 8.2 caecal worms, and 23.5 +/- 2.1 eyeworms and 129.9 +/- 10.7 caecal worms in 2015. Scaled quail averaged 4.8 +/- 1.0 eyeworms and 50 +/- 6.8 caecal worms in 2014, and 5.7 +/- 1.3 eyeworms and 38.1 +/- 7.1 caecal worms in 2015. This study expands the knowledge of parasitic infection in quail inhabiting the Rolling Plains of Texas. A significant difference was documented in O. petrowi infection between species but there was no significant difference in A. pennula between quail species. No significant difference was detected in parasite infection between the sexes of both northern bobwhite and scaled quail. This study also documented the highest reported O. petrowi infection in both species of quail. Additional research is needed on the life history and infection dynamics of O. petrowi and A. pennula infections to determine if there are individual- and/or population-level implications due to parasitic infection. PMID- 27677309 TI - Protective effects of reduced dynamin-related protein 1 against amyloid beta induced mitochondrial dysfunction and synaptic damage in Alzheimer's disease. AB - The purpose of our study was to understand the protective effects of reduced expression of dynamin-related protein (Drp1) against amyloid beta (Abeta) induced mitochondrial and synaptic toxicities in Alzheimer's disease (AD) progression and pathogenesis. Our recent molecular and biochemical studies revealed that impaired mitochondrial dynamics-increased mitochondrial fragmentation and decreased fusion in neurons from autopsy brains of AD patients and from transgenic AD mice and neurons expressing Abeta, suggesting that Abeta causes mitochondrial fragmentation in AD. Further, our recent co-immunoprecipitation and immunostaining analysis revealed that the mitochondrial fission protein Drp1 interacted with Abeta, and this interaction increased as AD progressed. Based on these findings, we hypothesize that a partial deficiency of Drp1 inhibits Drp1 Abeta interactions and protects Abeta-induced mitochondrial and synaptic toxicities, and maintains mitochondrial dynamics and neuronal function in AD neurons. We crossed Drp1+/- mice with APP transgenic mice (Tg2576 line) and created double mutant (APPXDrp1+/-) mice. Using real-time RT-PCR and immunoblotting analyses, we measured mRNA expressions and protein levels of genes related to the mitochondrial dynamics, mitochondrial biogenesis and synapses from 6-month-old Drp1+/-, APP, APPXDrp1+/- and wild-type (WT) mice. Using biochemical methods, we also studied mitochondrial function and measured soluble Abeta in brain tissues from all lines of mice in our study. Decreased mRNA expressions and protein levels of Drp1 and Fis1 (fission) and CypD (matrix) genes, and increased levels of Mfn1, Mfn2 and Opa1 (fusion), Nrf1, Nrf2, PGC1alpha, TFAM (biogenesis) and synaptophysin, PSD95, synapsin 1, synaptobrevin 1, neurogranin, GAP43 and synaptopodin (synaptic) were found in 6-month-old APPXDrp1+/- mice relative to APP mice. Mitochondrial functional assays revealed that mitochondrial dysfunction is reduced in APPXDrp1+/- mice relative to APP mice, suggesting that reduced Drp1enhances mitochondrial function in AD neurons. Sandwich ELISA assay revealed that soluble Abeta levels were significantly reduced in APPXDrp1+/- mice relative to APP mice, indicating that reduced Drp1 decreases soluble Abeta production in AD progression. These findings suggest that a partial reduction of Drp1 reduces Abeta production, reduces mitochondrial dysfunction, and maintains mitochondrial dynamics, enhances mitochondrial biogenesis and synaptic activity in APP mice. These findings may have implications for the development of Drp1 based therapeutics for AD patients. PMID- 27677311 TI - Prodigious plant methylomes. AB - Schmitz and colleagues recently investigated DNA methylation patterns in diverse flowering plant species, finding substantial variation in the extent and distribution of methylation in angiosperms.Please see related Research article: http://www.doi.org/10.1186/s13059-016-1059-0. PMID- 27677310 TI - Evaluation of self-swabbing coupled with a telephone health helpline as an adjunct tool for surveillance of influenza viruses in Ontario. AB - BACKGROUND: Calls to a telephone health helpline (THHL) have been previously evaluated for the ability to monitor specific syndromes, such as fever and influenza-like-illness or gastrointestinal illness. This method of surveillance has been shown to be highly correlated with traditional surveillance methods, and to have potential for early detection of community-based illness. Self-sampling, or having a person take his/her own nasal swab, has also proven successful as a useful method for obtaining a specimen, which may be used for respiratory virus detection. METHODS: This study describes a self-swabbing surveillance system mediated by a nurse-led THHL in Ontario whereby syndromic surveillance concepts are used to recruit and monitor participants with influenza-like illness. Once recruited, participants collect a nasal specimen obtained by self-swabbing and submit for testing and laboratory confirmation. Enumeration of weekly case counts was used to evaluate the timeliness of the self-swabbing surveillance system through comparison to other respiratory virus and influenza surveillance systems in Ontario. The operational efficiency of the system was also evaluated. RESULTS: The mean and median number of days between the day that a participant called the THHL, to the day a package was received at the laboratory for testing were approximately 10.4 and 8.6 days, respectively. The time between self-swab collection and package reception was 4.9 days on average, with a median of 4 days. The self-swabbing surveillance system adequately captured the 2014 influenza B season in a timely manner when compared to other Ontario-based sources of influenza surveillance data from the same year; however, the emergence of influenza B was not detected any earlier than with these other surveillance systems. Influenza A surveillance was also evaluated. Using the THHL self swabbing system, a peak in the number of cases for influenza A was observed approximately one week after or during the same week as that reported by the other surveillance systems. CONCLUSION: This one-year pilot study suggests that the THHL self-swabbing surveillance system has significant potential as an adjunct tool for the surveillance of influenza viruses in Ontario. Recommendations for improving system efficacy are discussed. PMID- 27677312 TI - Birth weight in relation to health and disease in later life: an umbrella review of systematic reviews and meta-analyses. AB - BACKGROUND: Birth weight, a marker of the intrauterine environment, has been extensively studied in epidemiological research in relation to subsequent health and disease. Although numerous meta-analyses have been published examining the association between birth weight and subsequent health-related outcomes, the epidemiological credibility of these associations has not been thoroughly assessed. The objective of this study is to map the diverse health outcomes associated with birth weight and evaluate the credibility and presence of biases in the reported associations. METHODS: An umbrella review was performed to identify systematic reviews and meta-analyses of observational studies investigating the association between birth weight and subsequent health outcomes and traits. For each association, we estimated the summary effect size by random effects and fixed-effects models, the 95 % confidence interval, and the 95 % prediction interval. We also assessed the between-study heterogeneity, evidence for small-study effects and excess significance bias. We further applied standardized methodological criteria to evaluate the epidemiological credibility of the statistically significant associations. RESULTS: Thirty-nine articles including 78 associations between birth weight and diverse outcomes met the eligibility criteria. A wide range of health outcomes has been studied, ranging from anthropometry and metabolic diseases, cardiovascular diseases and cardiovascular risk factors, various cancers, respiratory diseases and allergies, musculoskeletal traits and perinatal outcomes. Forty-seven of 78 associations presented a nominally significant summary effect and 21 associations remained statistically significant at P < 1 * 10-6. Thirty associations presented large or very large between-study heterogeneity. Evidence for small-study effects and excess significance bias was present in 13 and 16 associations, respectively. One association with low birth weight (increased risk for all-cause mortality), two dose-response associations with birth weight (higher bone mineral concentration in hip and lower risk for mortality from cardiovascular diseases per 1 kg increase in birth weight) and one association with small-for-gestational age infants with normal birth weight (increased risk for childhood stunting) presented convincing evidence. Eleven additional associations had highly suggestive evidence. CONCLUSIONS: The range of outcomes convincingly associated with birth weight might be narrower than originally described under the "fetal origin hypothesis" of disease. There is weak evidence that birth weight constitutes an effective public health intervention marker. PMID- 27677313 TI - Serum CA125 and HE4 levels as predictors for optimal interval surgery and platinum sensitivity after neoadjuvant platinum-based chemotherapy in patients with advanced epithelial ovarian cancer. AB - BACKGROUND: The aim of this study is to evaluate a new tumour marker, HE4, and to compare it with CA125 in predicting optimal cytoreduction and response to chemotherapy. Thirty patients with advanced epithelial ovarian cancer and multiple sera harvested during neoadjuvant chemotherapy (NAC) were included. RESULTS: Based on ROC curves analysis, CA125 <= 75 UI/ml and HE4 <= 252 pmol/L after the 3rd cycles of NAC, with a sensitivity of 93.7 % and a specificity of 92.3 % (PPV = 93.7 % and NPV = 92.3 %), offered the best combination for predicting optimal cytoreduction. In addition, the HE4 value of 115 pmol/L is the best cut-off level for identifying platinum-sensitive patients. CONCLUSIONS: The introduction of HE4 as a new tool for predicting platinum-sensitivity and interval optimal cytoreduction is promising. PMID- 27677315 TI - Label-Free Analysis and Sorting of Microalgae and Cyanobacteria in Microdroplets by Intrinsic Chlorophyll Fluorescence for the Identification of Fast Growing Strains. AB - Microalgae and cyanobacteria are promising organisms for sustainable biofuel production, but several challenges remain to make this economically viable, including identification of optimized strains with high biomass productivity. Here we report on a novel methodology for the label-free screening and sorting of cyanobacteria and microalgae in a microdroplet platform. We show for the first time that chlorophyll fluorescence can be used to measure differences in biomass between populations of picoliter microdroplets containing different species of cyanobacteria, Synechocystis PCC 6803 and Synechococcus PCC 7002, which exhibit different growth dynamics in bulk culture. The potential and robustness of this label-free screening approach is further demonstrated by the screening and sorting of cells of the green alga Chlamydomonas reinhardtii encapsulated in droplets. PMID- 27677314 TI - Serum Antibodies against Helicobacter pylori Neutrophil Activating Protein in Carriers of IL-4 C-590T Genetic Polymorphism Amplify the Risk of Gastritis and Gastric Cancer. AB - BACKGROUND: Gastric cancer arises, mainly, on an inflammatory background. Helicobacter pylori neutrophil activating (HP-NAP) protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators. METHODS: Gastritis (n=58) and gastric cancer (n=31) patients were evaluated and compared with H. pylori-positive asymptomatic controls (n=46), for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis. RESULTS: In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold (OR=4.62, 95% CI=1.50-14.22), which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold (OR=9.70, 95% CI=2.06-45.69). A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold (OR=9.07, 95% CI=1.99-42.0) for HP-NAP-seropositive subjects and was drastically amplified (OR=33.64, 95% CI=2.06-548.68), when double-positive (HP NAP seropositive/IL-4 -590 T carrier) subjects were examined against double negatives (HP-NAP seronegative/IL-4 -590 CC). CONCLUSION: Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility. PMID- 27677316 TI - Perioperative management of Parkinson's disease. AB - INTRODUCTION: Guidelines for the management of Parkinson's disease (PD) patients in the perioperative setting are lacking. Areas covered: Here we review potential problems that may arise when PD patients are undergoing an operation. We also review the literature, where available, and provide our expert opinion and recommendations based on experience. Expert commentary: Elderly patients with PD are especially prone to complications in the perioperative setting. Extreme caution must be used to ensure appropriate medication administration, transition to non-oral agents, if indicated, and early mobilization to achieve rapid recovery after surgery. PMID- 27677317 TI - Intrauterine hematomas in the second and third trimesters associated with adverse pregnancy outcomes: a retrospective study. AB - OBJECTIVE: To carry out a retrospective study of the clinical features of patients with intrauterine hematoma in the second and third trimesters, and discuss the risk factors for poor pregnancy outcomes. METHODS: A total of 398 patients who underwent routine examination in our hospital from January 2011 to December 2015 were classified into normal pregnancy (NP) group (N = 265) and adverse pregnancy (AP) group (N = 133), according to their pregnancy outcomes. Maternal clinical demographics, gestational age, location of hematoma, volume of hematoma, and accompanying contraction and vaginal bleeding were recorded. RESULTS: The average age of pregnant women in the NP and AP groups was 28.25 +/- 4.06 and 29.5 +/- 5.06 years, respectively (p = 0.007). Gestational age at first detection of hematoma was 15.11 +/- 5.13 weeks in the NP group compared with 21.22 +/- 8.25 weeks in the AP group (p < 0.001). In the AP group, the incidence of retroplacental hematoma (54.1%) and palpable contractions (62.8%) was significantly higher than in the NP group (25.7% and 12.1%, respectively; p < 0.01). However, similar maternal parity or history of delivery, volume of hematoma and incidence of vaginal bleeding were found. CONCLUSION: Intrauterine hematoma in the second and third trimesters is a sign of pathological pregnancy, resulting in adverse outcomes. Maternal age, gestational age at first diagnosis, location of hematoma and accompanying contraction are risk factors for poor pregnancy outcomes. PMID- 27677319 TI - Substituted indole Mcl-1 inhibitors: a patent evaluation (WO2015148854A1). AB - The myeloid cell leukemia 1 (Mcl-1) protein, an anti-apoptotic member of Bcl-2 family, plays a critical role in the development and maintenance of many cancers and is listed in the 'top ten' pathological factors across the diversity of human cancers. The patent described in this evaluation (WO2015148854A1) claimed substituted indole Mcl-1 inhibitors for the treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 proteins. A variety of 2-position substituents distinguished indole Mcl-1 inhibitors claimed in this patent from another two patents by AbbVie Inc. (WO2008131000A2 and WO2008130970A1). They exhibited low-nanomolar binding affinities and >100-fold selectivity over Bcl-2 and Bcl-xL in vitro, and low micromolar killing abilities against a panel of tumour cell lines. Moreover, the compounds in this patent revealed that the structural basis for selective Mcl-1 inhibitors may not completely depend on the 5 known binding hot-spots, and conformational flexibility of Mcl-1 protein could contribute to the binding specificity. PMID- 27677318 TI - Successful short-term re-learning and generalisation of concepts in semantic dementia. AB - Patients with semantic dementia (SD) can rapidly and successfully re-learn word labels during cognitive intervention. This new learning, however, usually remains rigid and context-dependent. Conceptual enrichment (COEN) training is a therapy approach aimed to produce more flexible and generalisable learning in SD. In this study we compare generalisation and maintenance of learning after COEN with performance achieved using a classical naming therapy (NT). The study recruited a 62-year-old woman with SD. An AB1ACAB2 experimental design was implemented, with naming performance assessed at baseline, post- intervention, 3 and 6 weeks after the end of each treatment phase. Three generalisation tasks were also assessed pre- and post-intervention. Naming post-intervention improved significantly following both therapies, however, words trained using COEN therapy showed a significantly greater degree of generalisation than those trained under NT. In addition, only words trained with COEN continued to show significant improvements compared with baseline performance when assessed 6 weeks after practice ceased. It was concluded that therapies based on conceptual enrichment of the semantic network facilitate relearning of words and enhance generalisation in patients with SD. PMID- 27677320 TI - Association of hypertension-related distress with lack of self-care among hypertensive patients. AB - Research on factors associated with poor adherence to self-care focuses primarily on psychiatric emotional disorders such as depression and anxiety, whereas non psychiatric chronic-disease-related emotional distress has received little attention in hypertensive patients. The objective of this study was to evaluate the association of hypertension-related distress with the lack of self-care including low adherence to pharmacological treatment, lack of regular physical activity, low intake of fruits and vegetables and frequent intake of high-salt foods. A cross-sectional survey was conducted in 2014 in two family medical units affiliated with the Mexican Institute of Social Security. The study included 487 hypertensive patients >19 years of age. The conceptual framework for the study was based on the Health Promotion Model. The analysis included multiple Poisson regression models. We found that 21.1% of participants had hypertension-related distress. Low adherence to pharmacological treatment was identified in 45.8% of patients, whereas 46.8% lacked regular physical activity, 30.8% reported a low consumption of fruits and vegetables, and 54.6% frequently consumed foods high in salt content. Hypertension-related distress was associated with lack of regular physical activity and low intake of fruits and vegetables. These findings highlight the importance of addressing distress in order to improve self-care of hypertensive patients. PMID- 27677321 TI - Which type of social activities may reduce cognitive decline in the elderly?: a longitudinal population-based study. AB - BACKGROUND: Previous studies have found that social activities are beneficial for the reduction of cognitive decline (CD) in the elderly. However, knowledge regarding the types of social activities that reduce CD in later life is limited. The aim of this study is to examine which type of social activities reduce CD 4 years later among young-old (Y-O) and old-old (O-O) adults. METHODS: We conducted a secondary analysis using data from cognitively intact adults 65 years of age or older who participated in the Korean Longitudinal Study of Aging (KLoSA). Cognitive function was assessed using the Korean version of the Mini-Mental State Examination (MMSE). We computed CD between 2008 and 2012 by subtracting the Wave 4 MMSE score from the Wave 2 MMSE score. Multivariate linear regression analysis was conducted regarding the effects of social activities on CD after adjusting for age, sex, education, income, marital status, activities of daily living (ADL), instrumental activities of daily living (IADL), chronic diseases, quality of life, depressive symptom, change in depressive symptom, and cognitive functioning at baseline. RESULTS: Subjects who participated in senior citizen clubs or senior centers at baseline had a lower risk of CD 4 years later than those who did not in Y-O adults. Frequent contact with offspring by phone or letters was associated with reduced CD in O-O adults. Frequent face-to-face contact with offspring was positively associated with CD in O-O adults. Participating in two or more formal social activities was associated with reduced CD compared with nonparticipation in O-O adults. CONCLUSION: Encouraging older adults to participate in senior citizen clubs or to have frequent contacts with adult children by phone or letters may help reduce CD in later life among older adults. Participation in a variety of formal social activities may also have a beneficial effect on preventing CD in older adults. PMID- 27677322 TI - Synthesis and anticancer and lipophilic properties of 10-dialkylaminobutynyl derivatives of 1,8- and 2,7-diazaphenothiazines. AB - New derivatives of two isomeric types of azaphenothiazines, 1,8- and 2,7 diazaphenothiazine, containing the triple bond substituents and additionally tertiary cyclic and acyclic amine groups, were synthesized and tested for their anticancer activity. The compounds exhibited differential inhibitory activities. Better results were obtained when the acetylenic group was transformed via the Mannich reaction to the dialkylaminobutynyl groups. The most active was 2,7 diazaphenothiazine with the N-methylpiperazine-2-butynyl substituent against the human ductal breast epithelial tumor cell line T47D, more potent than cisplatin. The 2,7-diazaphenothiazine system turned out to be more active than isomeric 1,8 diaza one. For the most active compound, the expression of TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The gene expression ratio BACL 2/BAX suggests the mitochondrial apoptosis in T47D cells. The synthesis makes possible to obtain many new bioactive phenothiazines with the dialkylaminoalkynyl substituents inserting various tertiary cyclic and acyclic amine moieties to the substituents. PMID- 27677324 TI - Testicular parameters and spermatogenesis in different birthweight boars. AB - The present study investigated the effect of birthweight on testicular development and spermatogenesis in boars. Twenty-four pairs of littermate boars were selected: one piglet with the highest birthweight (HW) and the other with the lowest birthweight (LW) within the litter. Two subsets of 12 pairs of male littermates from each birthweight group were obtained after selection: one subset was orchiectomised at 8 days and the other at 8 months of age. HW boars had higher body and testicular weights at both ages (P<0.05). Testosterone concentrations and the relative expression of 17alpha-hydroxylase in the testis were similar between birthweight groups. Birthweight affected somatic and germ cell numbers in the neonatal testis, which were higher in HW boars (P<0.05). Moreover, a significant reduction in the number of pachytene spermatocytes and round spermatids was observed in LW boars (P<0.05) at 8 months of age, which caused a decrease in the total number of elongated spermatids and daily sperm production (P<0.05). Hence, HW boars have the potential to produce more spermatozoa and consequently more semen doses per ejaculate, and would be very valuable to an industry that relies on AI. PMID- 27677325 TI - Response to Cognitive impulsivity and the behavioral addiction model of obsessive compulsive disorder: Abramovitch and McKay (2016). AB - In our recently published article, we investigated the behavioral addiction model of obsessive-compulsive disorder (OCD), by assessing three core dimensions of addiction in patients with OCD healthy participants. Similar to the common findings in addiction, OCD patients demonstrated increased impulsivity, risky decision-making, and biased probabilistic reasoning compared to healthy controls. Thus, we concluded that these results support the conceptualization of OCD as a disorder of behavioral addiction. Here, we answer to Abramovitch and McKay (2016) commentary on our paper and we support our conclusions by explaining how cognitive impulsivity is also a typical feature of addiction and how our results on decision-making and probabilistic reasoning tasks reflect cognitive impulsivity facets that are consistently replicated in OCD and addiction. PMID- 27677326 TI - V2O5-C-SnO2 Hybrid Nanobelts as High Performance Anodes for Lithium-ion Batteries. AB - The superior performance of metal oxide nanocomposites has introduced them as excellent candidates for emerging energy sources, and attracted significant attention in recent years. The drawback of these materials is their inherent structural pulverization which adversely impacts their performance and makes the rational design of stable nanocomposites a great challenge. In this work, functional V2O5-C-SnO2 hybrid nanobelts (VCSNs) with a stable structure are introduced where the ultradispersed SnO2 nanocrystals are tightly linked with glucose on the V2O5 surface. The nanostructured V2O5 acts as a supporting matrix as well as an active electrode component. Compared with existing carbon-V2O5 hybrid nanobelts, these hybrid nanobelts exhibit a much higher reversible capacity and architectural stability when used as anode materials for lithium-ion batteries. The superior cyclic performance of VCSNs can be attributed to the synergistic effects of SnO2 and V2O5. However, limited data are available for V2O5-based anodes in lithium-ion battery design. PMID- 27677327 TI - Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury. AB - Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID- 27677329 TI - Electrical detection and quantification of single and mixed DNA nucleotides in suspension. AB - High speed sequential identification of the building blocks of DNA, (deoxyribonucleotides or nucleotides for short) without labeling or processing in long reads of DNA is the need of the hour. This can be accomplished through exploiting their unique electrical properties. In this study, the four different types of nucleotides that constitute a DNA molecule were suspended in a buffer followed by performing several types of electrical measurements. These electrical parameters were then used to quantify the suspended DNA nucleotides. Thus, we present a purely electrical counting scheme based on the semiconductor theory that allows one to determine the number of nucleotides in a solution by measuring their capacitance-voltage dependency. The nucleotide count was observed to be similar to the multiplication of the corresponding dopant concentration and debye volume after de-embedding the buffer contribution. The presented approach allows for a fast and label-free quantification of single and mixed nucleotides in a solution. PMID- 27677330 TI - The Evolution of Generosity in the Ultimatum Game. AB - When humans fail to make optimal decisions in strategic games and economic gambles, researchers typically try to explain why that behaviour is biased. To this end, they search for mechanisms that cause human behaviour to deviate from what seems to be the rational optimum. But perhaps human behaviour is not biased; perhaps research assumptions about the optimality of strategies are incomplete. In the one-shot anonymous symmetric ultimatum game (UG), humans fail to play optimally as defined by the Nash equilibrium. However, the distinction between kin and non-kin-with kin detection being a key evolutionary adaption-is often neglected when deriving the "optimal" strategy. We computationally evolved strategies in the UG that were equipped with an evolvable probability to discern kin from non-kin. When an opponent was not kin, agents evolved strategies that were similar to those used by humans. We therefore conclude that the strategy humans play is not irrational. The deviation between behaviour and the Nash equilibrium may rather be attributable to key evolutionary adaptations, such as kin detection. Our findings further suggest that social preference models are likely to capture mechanisms that permit people to play optimally in an evolutionary context. Once this context is taken into account, human behaviour no longer appears irrational. PMID- 27677328 TI - Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans. AB - Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets. PMID- 27677331 TI - Allosteric Inhibitory Molecular Recognition of a Photochromic Dye by a Digestive Enzyme: Dihydroindolizine makes alpha-chymotrypsin Photo-responsive. AB - The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease alpha-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo controlled manner. Simultaneous binding of the well-known inhibitors 4 nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Forster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1 Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity. PMID- 27677332 TI - Non-cell autonomous cues for enhanced functionality of human embryonic stem cell derived cardiomyocytes via maturation of sarcolemmal and mitochondrial KATP channels. AB - Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (KATP) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcKATP and mitoKATP in hESC-VCM. We showed that SarcIK, ATP in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known opener P1075 with a current density that was ~8-fold smaller than adult; These effects were reversible upon washout or the addition of GLI or HMR1098. Interestingly, sarcIK, ATP displayed a ~3-fold increase after treatment with hypoxia (5% O2). MitoIK, ATP was absent in hESC VCMs. However, the thyroid hormone T3 up-regulated mitoIK, ATP, conferring diazoxide protective effect on T3-treated hESC-VCMs. When assessed using a multi cellular engineered 3D ventricular cardiac micro-tissue (hvCMT) system, T3 substantially enhanced the developed tension by 3-folds. Diazoxide also attenuated the decrease in contractility induced by simulated ischemia (1% O2). We conclude that hypoxia and T3 enhance the functionality of hESC-VCMs and their engineered tissues by selectively acting on sarc and mitoIK, ATP. PMID- 27677333 TI - Unravelling molecular mechanisms from floral initiation to lipid biosynthesis in a promising biofuel tree species, Pongamia pinnata using transcriptome analysis. AB - Pongamia pinnata (L.) (Fabaceae) is a promising biofuel tree species which is underexploited in the areas of both fundamental and applied research, due to the lack of information either on transcriptome or genomic data. To investigate the possible metabolic pathways, we performed whole transcriptome analysis of Pongamia through Illumina NextSeq platform and generated 2.8 GB of paired end sequence reads. The de novo assembly of raw reads generated 40,000 contigs and 35,000 transcripts, representing leaf, flower and seed unigenes. Spatial and temporal expression profiles of photoperiod and floral homeotic genes in Pongamia, identified GIGANTEA (GI) - CONSTANS (CO) - FLOWERING LOCUS T (FT) as active signal cascade for floral initiation. Four prominent stages of seed development were selected in a high yielding Pongamia accession (TOIL 1) to follow the temporal expression patterns of key fatty acid biosynthetic genes involved in lipid biosynthesis and accumulation. Our results provide insights into an array of molecular events from flowering to seed maturity in Pongamia which will provide substantial basis for modulation of fatty acid composition and enhancing oil yields which should serve as a potential feedstock for biofuel production. PMID- 27677336 TI - [Considerations on avoidable hospitalizations by heart failure. Related variables]. PMID- 27677334 TI - Embryonic type Na+ channel beta-subunit, SCN3B masks the disease phenotype of Brugada syndrome. AB - SCN5A is abundant in heart and has a major role in INa. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation. Here we show that electrophysiological analysis revealed that LQTS3/BrS iPSC-derived cardiomyocytes recapitulate the phenotype of LQTS3 but not BrS. Each beta-subunit of the sodium channel is differentially expressed in embryonic and adult hearts. SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. A heterologous expression system revealed that INa of mutated SCN5A is decreased and SCN3B augmented INa of mutated SCN5A. Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes successfully unmasked the phenotype of BrS. Isogenic control of LQTS3/BrS (corrected-LQTS3/BrS) iPSC-derived cardiomyocytes gained the normal electrophysiological properties. PMID- 27677337 TI - Molecular Filtration by Ultrathin and Highly Porous Silica Nanochannel Membranes: Permeability and Selectivity. AB - An ideal molecular filtration membranes should be highly permeable and selective, thus desiring the membranes to be ultrathin, be highly porous, and consists of small and uniform pores or channels. In this work, we report the molecular filtration by free-standing ultrathin silica nanochannel membranes (SNMs) using a U-shaped cell and spectrophotometric detection, focusing on the quantitative evaluation of permeability and selectivity of SNMs. Thanks to the ultrasmall channel size, namely, ~2-3 nm, and the negatively charged channel surface arising from the deprotonation of silanol groups, the SNM displayed excellent size and charge selectivity for molecular filtration. The selectivity coefficient for separation of small methyl viologen from large cytochrome c is as high as 273, because of the uniform pore/channel size. The charge-based filtration can be modulated by the salt concentration and solution pH, which control the overlap of radial electrical double layer and surface charge sign/density, respectively. Owing to the high relative pore density, namely, 16.7%, and the straight and vertical channel orientation, the SNM is highly permeable, displaying a molecule flux much higher than commercially available dialysis membrane and others reported previously. In addition, we demonstrated that, by biasing a small voltage across the SNM, both the flux and separation selectivity could be significantly enhanced. PMID- 27677335 TI - Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. AB - Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4alpha. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression. PMID- 27677338 TI - Non food-related risk factors of campylobacteriosis in Canada: a matched case control study. AB - BACKGROUND: Campylobacteriosis is a prominent bacterial gastrointestinal infection worldwide with several transmission pathways. Its non-foodborne routes have been less documented and quantified. The study aimed to quantitatively explore the role of potential risk factors not directly associated with food for sporadic cases of C. jejuni infection in Canada. METHODS: This retrospective matched case-control study was built on an enhanced campylobacteriosis surveillance system and on a survey of healthy people and their behaviour with regards to potential risk factors for gastrointestinal infections that occurred in the same area in Canada. Eighty-five cases were individually matched by age and season to 170 controls. RESULTS: Through conditional logistic regression, risk factors were found only among water-related factors (drinking untreated water, using tap filter, drinking water from well and swimming in natural water), whereas drinking bottled water was protective. Among the 32 non-water related factors explored, 12 were surprisingly 'protective' factors without relevant explanation for that effect (for example gardening, attending a barbecue, eating food from a fast-food restaurant), suggesting that human infection by Campylobacter may be more frequently acquired at home than outside the home. CONCLUSIONS: This study confirms and quantifies the importance of the waterborne transmission of campylobacteriosis. People are encouraged to drink only treated water and to avoid the ingestion of natural water as much as possible while swimming or playing in water. Globally, general hygiene and proper food handling and cooking practices at home should continue to be encouraged. PMID- 27677341 TI - How Parallel Are Excited State Potential Energy Surfaces from Time-Independent and Time-Dependent DFT? A BODIPY Dye Case Study. AB - To support the development and characterization of chromophores with targeted photophysical properties, excited-state electronic structure calculations should rapidly and accurately predict how derivatization of a chromophore will affect its excitation and emission energies. This paper examines whether a time independent excited-state density functional theory (DFT) approach meets this need through a case study of BODIPY chromophore photophysics. A restricted open shell Kohn-Sham (ROKS) treatment of the S1 excited state of BODIPY dyes is contrasted with linear-response time-dependent density functional theory (TDDFT). Vertical excitation energies predicted by the two approaches are remarkably different due to overestimation by TDDFT and underestimation by ROKS relative to experiment. Overall, ROKS with a standard hybrid functional provides the more accurate description of the S1 excited state of BODIPY dyes, but excitation energies computed by the two methods are strongly correlated. The two approaches also make similar predictions of shifts in the excitation energy upon functionalization of the chromophore. TDDFT and ROKS models of the S1 potential energy surface are then examined in detail for a representative BODIPY dye through molecular dynamics sampling on both model surfaces. We identify the most significant differences in the sampled surfaces and analyze these differences along selected normal modes. Differences between ROKS and TDDFT descriptions of the S1 potential energy surface for this BODIPY derivative highlight the continuing need for validation of widely used approximations in excited state DFT through experimental benchmarking and comparison to ab initio reference data. PMID- 27677340 TI - Intussusception hospitalizations incidence in the pediatric population in Italy: a nationwide cross-sectional study. AB - BACKGROUND: Study to investigate the intussusception incidence background in the pediatric population and its temporal trend in Italy. METHODS: A cross-sectional study was conducted on the pediatric population aged 0 to 15 years, in the period 1 January 2002 to 31 December 2012. Intussusception cases were identified using the national hospital discharge database. The annual intussusception incidence, the incidence rate ratios (IRRs) and the related 95 % confidence Intervals (CI) were calculated. RESULTS: The overall intussusception incidence rate was 21 per 100,000 children aged <=15 years, and was higher among boys than girls. The highest intussusception incidence rate occurred in infants <1 year of age (39 per 100,000 infants). Among infants, incidence varied with the geographical area, with higher rates in the central Italy (50 per 100,000 infants). The annual incidence rates in infants were stable since 2004 and up to 2012, ranging from 40.1 and 33.0 per 100,000 infants. Similar stable patterns were observed when conducting the analysis on children over 1 year of age. CONCLUSIONS: This study provided the intussusception incidence background in Italy in different pediatric ages, including infants, over an 11-year period. This information is essential in post-marketing safety surveillance, to continuously monitor the benefit/risk profile of rotavirus vaccinations. PMID- 27677339 TI - Extracellular ATP is involved in dsRNA-induced MUC5AC production via P2Y2R in human airway epithelium. AB - BACKGROUND: In response to tissue damage or inflammation, adenosine-5' triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations. METHODS: The involvement of extracellular ATP in the release of a major airway mucin, MUC5AC, and its signal pathway was examined after stimulation with polyinosine polycytidylic acid [poly(I:C)], a synthetic analog of dsRNA to mimic viral infection, and rhinovirus (RV) infection in NCI-H292 cells and differentiated airway epithelial cells from COPD patients. RESULTS: Treatment with poly(I:C) significantly increased the amount of extracellular ATP and induced MUC5AC release in NCI-H292 cells. Pre-treatment with a pannexin channel inhibitor, carbenoxolone (CBX), reduced the amount of extracellular ATP and suppressed MUC5AC release from poly(I:C)-treated cells. Pre-treatment with the P2R antagonist suramin significantly reduced the expression and release of MUC5AC. The inhibitory effects of CBX and suramin on the release of ATP and/or MUC5AC were replicated with RV infection. Pre-treatment with suramin also significantly reduced the expression and amount of extracellular EGFR ligands and the phosphorylation of EGFR and ERK in poly(I:C)-treated cells. In addition, pre treatment with a P2Y2 receptor siRNA significantly suppressed the poly(I:C) potentiated EGFR ligands and MUC5AC release. After poly(I:C) stimulation, the expression of MUC5AC in the differentiated cells from COPD patients was significantly higher than those from healthy subjects and the values of MUC5AC expression were inversely related with forced expiratory volume in 1 s (FEV1) % predicted. The inhibitory effects of CBX and suramin on poly(I:C)-potentiated MUC5AC expression were confirmed in differentiated airway epithelium from COPD patients. CONCLUSIONS: These results demonstrate that dsRNA induces the release of ATP via pannexin channel and that the extracellular ATP is involved in the expression and release of MUC5AC, mainly via P2Y2R, in an autocrine manner. Modulation of this pathway could be a therapeutic target for viral-induced mucus hypersecretion in COPD exacerbations. PMID- 27677342 TI - Group B Streptococcus late onset sepsis in very low birth weight newborns: 10 years experience. AB - PURPOSE: The incidence of late-onset neonatal infection (LONS) group B streptococcus (GBS) in very low birth weight (VLBW) is still matter of debate. In the present 10-years retrospective study we investigated the epidemiology of GBS LONS in VLBW neonates. MATERIALS AND METHODS: From January 2006 to July 2015 we conducted a retrospective study in all preterm infants admitted at our third level referral center for neonatal intensive care (NICU). From our database we were able to retrieve all cases of bloodstream infections/meningitis GBS positive. Perinatal data were also collected Results: On a total of 13 747 infants 975 (7%) were VLBW and in seven cases of GBS LONS was observed with a incidence of 7.2/1000 live births. CONCLUSIONS: The higher rate of LONS GBS in our series offer additional support to further investigations in wider population in order to better define GBS screening and therapeutic management in a such specific population. PMID- 27677343 TI - Living with Parkinson's disease: A Jordanian perspective. AB - BACKGROUND: Parkinson's disease (PD) has a major impact on mobility, as well as cognition which can consequently impair aspects of individual's lives. Many studies have examined the living experiences of individuals with PD and its impact on their daily lives. None of these studies have explored the life experiences of Jordanian individuals living with PD. Therefore, the purpose of this qualitative study was to describe the daily living experiences and impact on lives of Jordanian individuals with PD. METHODS: A qualitative phenomenological design was used. Interviews were recorded and transcribed. Transcripts were analysed using thematic analysis. RESULTS: Experiences of 8 Jordanian individuals with PD who participated in this study can be categorized in the following major themes: (1) challenging perspectives and (2) adaptations. Challenging perspectives included stigma, emotional drainer, and experience of decreased independence and difficulty in occupational performance. Adaptations included embracing early acceptance and intervention, spiritual experience, and family support. CONCLUSIONS: Study provided a wealth of knowledge related to the effect of PD and its intersection with the Arabic Jordanian culture. Such knowledge should aid healthcare professionals involved with providing services to Jordanian individuals with PD to provide better holistic services. PMID- 27677344 TI - Tactical combat movements: inter-individual variation in performance due to the effects of load carriage. AB - An examination into the effects of carried military equipment on the performance of two tactical combat movement simulations was conducted. Nineteen Airfield Defence Guards performed a break contact (five 30-m sprints) and a fire and movement simulation (16 6-m bounds) in five load conditions (10-30 kg). Heavier loads significantly increased movement duration on the break contact (0.8%/kg load) and fire and movement (1.1%/kg). Performance deterioration was observed from the beginning to the end of the series of movements (bounds or sprints) with deterioration becoming significantly greater in heavier load conditions. Inter individual variation between slower and faster participants showed a range in load effects; 0.6, 0.8%/kg for fast and 1.0, 1.4%/kg for slow (break contact, fire and movement, respectively). Velocity profiles revealed that the initial acceleration and peak velocity were the primary determinants of performance. As the duration of these tactical combat movements reflects periods of heightened vulnerability, these findings highlight important implications for commanders. Practitioner Summary: Increasing amounts of carried military equipment impairs the performance of tactical combat movements. Examination of inter-individual variation in velocity profiles identified that the initial acceleration and the peak velocity achieved during sprints and bounds are key determinants of overall performance. PMID- 27677345 TI - Sexuality in individuals with traumatic brain injury and their partners. AB - Whilst previous research has detailed the impact of TBI on an individual's sexuality, few studies have investigated couples' sexuality where one partner has sustained a TBI. The study assessed sexual function in individuals with TBI and their partners. Fifty five individuals who had sustained TBI and their partners completed the Derogatis Interview for Sexual Function-Self Report (DISF-SR). All participants scored below the 50th percentile in relation to norms. Whilst participants with TBI obtained lower T-scores than partners on all subscales (except for sexual behaviour/experiences where scores were equivalent), as well as the total score, none of these differences was significant. Item analysis indicated that female participants with TBI reported significantly lower scores than female partners on frequency of having normal lubrication. Normative comparisons revealed that approximately one-third of individuals with TBI and one fifth of their partners scored below the second percentile. Given the high frequency of sexual problems in individuals with TBI, which also impact their partners, addressing sexual problems should be a priority in rehabilitation and beyond. PMID- 27677346 TI - Curcumin synergistically increases effects of beta-interferon and retinoic acid on breast cancer cells in vitro and in vivo by up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways. AB - OBJECTIVE: The study aimed to investigate the effects of combination treatment of curcumin and beta-interferon (IFN-beta)/retinoic acid (RA) on breast cancer cells, including cell viability, apoptosis and migration, and to determine the mechanisms related to GRIM-19 through STAT3-dependent and STAT3-independent pathways. METHODS: The following groups were used for the in vitro experiment: control siRNA, GRIM-19 siRNA, IFN-beta/RA and IFN-beta/RA + curcumin. Cell viability is by the MTT method, cell apoptosis by flow cytometry and cell migration by wound healing experiment; GRIM-19, STAT3, survivin, Bcl-2, GADD153 and COX-2 expression was measured by Western blot. In vivo experiment, MCF-7 cells were subcutaneously injected into nude mice. RESULTS: GRIM-19 siRNA promoted MCF-7 cell proliferation and migration; inhibited cell apoptosis; and promoted the expression of STAT3, survivin, Bcl-2 and MMP-9. IFN-beta/RA inhibited cell proliferation and migration; promoted cell apoptosis; up-regulated GRIM-19; and inhibited the expression of STAT3, survivin, Bcl-2 and MMP-9. Combination treatment of curcumin and IFN-beta/RA had a stronger effect than that of the IFN-beta/RA group. In addition, curcumin and IFN-beta/RA combination inhibited the expression of COX-2 and up-regulated GADD153. CONCLUSION: Curcumin synergistically increases the effects of IFN-beta/RA on breast cancer cells. The mechanism may be related to the up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways. PMID- 27677347 TI - A comparison of the peri-implant bone stress generated by the preload with screw tightening between 'bonded' and 'contact' model. AB - A number of finite element analyses (FEAs) for the dental implant were performed without regard for preload and with all interfaces 'fixed-bonded'. The purpose of this study was comparing the stress distributions between the conventional FEA model with all contacting interfaces 'fixed-bonded' (bonded model) and the model with the interfaces of the components in 'contact' with friction simulated as a preloaded implant (contact model). We further verified the accuracy of the result of the FEA using model experiment. In the contact model, the stress was more widely distributed than in the bonded model. From the model study, the preload induced by screw tightening generated strain at the peri-implant bone, even before the application of external force. As a result, the bonded model could not reproduce the mechanical phenomena, whereas the contact model is considered to be appropriate for analysing mechanical problems. PMID- 27677348 TI - Sperm antioxidant defences decrease during epididymal transit from caput to cauda in parallel with increases in epididymal fluid in the goat (Capra hircus). AB - The status of antioxidant defences of both spermatozoa and their associated fluids during epididymal transit from the caput to cauda have not been studied so far in any species. Herein we report for the first time that sperm antioxidant defences, namely Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase activity, decrease significantly (P<0.05) from the caput to cauda during epididymal transit in parallel with increases in Cu,Zn-SOD, total SOD and total glutathione peroxidase (GPx) activity in the luminal fluid of the respective segments. However, levels of GPX1 and GPX3 in epididymal fluid did not change significantly from the caput to cauda. Catalase was detected for the first time in goat spermatozoa. A significantly higher total antioxidant capacity of caudal fluid than of the caput suggests a requirement for a rich antioxidant environment for the storage of spermatozoa. The retention of cytoplasmic droplets in most of the caudal spermatozoa confirmed that these droplets do not contribute to the increased antioxidant defences of cauda epididymidal fluid. Thus, the antioxidant defences of the spermatozoa and their associated epididymal fluid are modulated from the caput to cauda in a region-specific manner. This may be one of the compensatory mechanisms of epididymal fluid to scavenge any excess reactive oxygen species produced in the microenvironment of spermatozoa. PMID- 27677349 TI - Advances in pharmacotherapy for erectile dysfunction and associated cardiac impact. AB - INTRODUCTION: Cardiovascular disease (CVD) and erectile dysfunction (ED) are two disease processes that affect millions of men. CVD and ED are increasingly recognized as sharing a common pathophysiologic origin. As the nature of this relationship continues to be elucidated, there is growing interest in developing a therapy to effectively target both processes. While researchers have largely focused on phosphodiesterase-5 inhibitors (PDE5Is), the established first-line therapy for ED, newer ED drugs, designed based on better understanding of the physiology of erection, may also show promise. Areas covered: This paper will review the relationship between ED and CVD, as well as the currently available and investigational pharmacologic treatments for ED. The particular focus will be on the role that these therapies play in managing CVD. Expert opinion: PDE5Is, along with the newer ED therapies, are promising candidates for managing ED and concurrently providing cardioprotection. Despite some in vitro success with PDE5Is, maxi-K channel activators, and guanylyl cyclase (GC) stimulators, in vivo studies have either been lacking, or shown conflicting results. More well designed clinical studies are needed in order to characterize an ED pharmacotherapy that offers proven cardioprotection. PMID- 27677350 TI - Types of gambling and levels of harm: A UK study to assess severity of presentation in a treatment-seeking population. AB - Background and aim Previous international research emphasized that some forms of gambling are more "addictive" than others. More recently, research has shown that we should shift our attention from the type of gambling activity to the level of involvement in a number of different gambling activities. The aim of our study was to verify whether a higher Problem Gambling Severity Index (PGSI) score was associated with particular gambling activities and evaluate the impact of involvement on gambling behavior. Methods A total of 736 treatment-seeking individuals with gambling disorder were assessed at the National Problem Gambling Clinic in London. First, the independent two-sample t-test and the Mann-Whitney test were used to verify if the PGSI score changed significantly according to the gambling activity at a bivariate level. Second, we conducted a cluster analysis and finally, we fitted a linear regression model in order to verify if some variables are useful to predict gambling addiction severity. Results The PGSI score was significantly higher for lower stakes gaming machine gamblers (1% significance level) and for fixed-odds betting terminal (FOBT) gamblers (5% significance level) at a bivariate level. Moreover, such finding was confirmed by cluster and linear regression analyses. Conclusions The results of this study indicated that gambling addiction severity was related to gambling involvement and, for a given level of gambling involvement, gambling addiction severity may vary according to gambling type, with a particularly significant increase for FOBT and gaming machine gambling. PMID- 27677351 TI - Inhibition of hypothalamic MCT1 expression increases food intake and alters orexigenic and anorexigenic neuropeptide expression. AB - Hypothalamic glucosensing, which involves the detection of glucose concentration changes by brain cells and subsequent release of orexigenic or anorexigenic neuropeptides, is a crucial process that regulates feeding behavior. Arcuate nucleus (AN) neurons are classically thought to be responsible for hypothalamic glucosensing through a direct sensing mechanism; however, recent data has shown a metabolic interaction between tanycytes and AN neurons through lactate that may also be contributing to this process. Monocarboxylate transporter 1 (MCT1) is the main isoform expressed by tanycytes, which could facilitate lactate release to hypothalamic AN neurons. We hypothesize that MCT1 inhibition could alter the metabolic coupling between tanycytes and AN neurons, altering feeding behavior. To test this, we inhibited MCT1 expression using adenovirus-mediated transfection of a shRNA into the third ventricle, transducing ependymal wall cells and tanycytes. Neuropeptide expression and feeding behavior were measured in MCT1 inhibited animals after intracerebroventricular glucose administration following a fasting period. Results showed a loss in glucose regulation of orexigenic neuropeptides and an abnormal expression of anorexigenic neuropeptides in response to fasting. This was accompanied by an increase in food intake and in body weight gain. Taken together, these results indicate that MCT1 expression in tanycytes plays a role in feeding behavior regulation. PMID- 27677352 TI - Mature neural responses to Infant-Directed Speech but not Adult-Directed Speech in Pre-Verbal Infants. AB - Infant directed speech (IDS), the speech register adults use when talking to infants, has been shown to have positive effects on attracting infants' attention, language learning, and emotional communication. Here event related potentials (ERPs) are used to investigate the neural coding of IDS and ADS (adult directed speech) as well as their discrimination by both infants and adults. Two instances of the vowel /i/, one extracted from ADS and one from IDS, were presented to 9-month-old infants and adults in two oddball conditions: ADS standard/IDS deviant and IDS standard/ADS deviant. In Experiment 1 with adults, the obligatory ERPs that code acoustic information were different for ADS and IDS; and discrimination, indexed by mismatch negativity (MMN) responses, showed that IDS and ADS deviants were discriminated equally well; although, the P3a response was larger for IDS suggesting it captured adults' attention more than did ADS. In infants the obligatory responses did not differ for IDS and ADS, but for discrimination, while IDS deviants generated both a slow-positive mismatch response (MMR) as well as an adult-like MMN, the ADS deviants generated only an MMR. The presence of a mature adult-like MMN suggests that the IDS stimulus is easier to discriminate for infants. PMID- 27677353 TI - A novel perovskite oxide chemically designed to show multiferroic phase boundary with room-temperature magnetoelectricity. AB - There is a growing activity in the search of novel single-phase multiferroics that could finally provide distinctive magnetoelectric responses at room temperature, for they would enable a range of potentially disruptive technologies, making use of the ability of controlling polarization with a magnetic field or magnetism with an electric one (for example, voltage-tunable spintronic devices, uncooled magnetic sensors and the long-searched magnetoelectric memory). A very promising novel material concept could be to make use of phase-change phenomena at structural instabilities of a multiferroic state. Indeed, large phase-change magnetoelectric response has been anticipated by a first-principles investigation of the perovskite BiFeO3-BiCoO3 solid solution, specifically at its morphotropic phase boundary between multiferroic polymorphs of rhombohedral and tetragonal symmetries. Here, we report a novel perovskite oxide that belongs to the BiFeO3-BiMnO3-PbTiO3 ternary system, chemically designed to present such multiferroic phase boundary with enhanced ferroelectricity and canted ferromagnetism, which shows distinctive room temperature magnetoelectric responses. PMID- 27677354 TI - Investigating Energetic X-Shaped Flares on the Outskirts of A Solar Active Region. AB - Typical solar flares display two quasi-parallel, bright ribbons on the chromosphere. In between is the polarity inversion line (PIL) separating concentrated magnetic fluxes of opposite polarity in active regions (ARs). Intriguingly a series of flares exhibiting X-shaped ribbons occurred at the similar location on the outskirts of NOAA AR 11967, where magnetic fluxes were scattered, yet three of them were alarmingly energetic. The X shape, whose center coincided with hard X-ray emission, was similar in UV/EUV, which cannot be accommodated in the standard flare model. Mapping out magnetic connectivities in potential fields, we found that the X morphology was dictated by the intersection of two quasi-separatrix layers, i.e., a hyperbolic flux tube (HFT), within which a separator connecting a double null was embedded. This topology was not purely local but regulated by fluxes and flows over the whole AR. The nonlinear force free field model suggested the formation of a current layer at the HFT, where the current dissipation can be mapped to the X-shaped ribbons via field-aligned heat conduction. These results highlight the critical role of HFTs in 3D magnetic reconnection and have important implications for astrophysical and laboratory plasmas. PMID- 27677356 TI - Phase-dependent dynamic potential of magnetically coupled two-degree-of-freedom bistable energy harvester. AB - A system of magnetically coupled oscillators has been recently considered as a promising compact structure to integrate multiple bistable energy harvesters (BEHs), but its design is not straightforward owing to its varying potential energy pattern, which has not been understood completely yet. This study introduces the concept of phase-dependent dynamic potential in a magnetically coupled BEH system with two degrees of freedom (DOFs) to explain the underlying principle of the complicated dynamics of the system. Through theoretical simulations and analyses, two distinct dynamic regimes, called the out-of-phase and in-phase mode regimes in this report, are found to exist in the frequency regions of the 1st and 2nd primary intrawell resonances. For the out-of-phase mode regime, the frequency displacement (and output power) responses of the 2-DOF BEH system exhibit typical double-well dynamics, whereas for the in-phase mode regime, only single-well dynamics is observed though the system is statically bistable. These dynamic regimes are also revealed to be caused by the difference in the dynamic potential energy trajectories propagating on a high-dimensional potential energy surface. The present approach to the dynamics of the 2-DOF BEH system can be extended and applied to higher-DOF systems, which sheds light on compact and efficient designs of magnetically coupled BEH chain structures. PMID- 27677355 TI - In Utero Caffeine Exposure Induces Transgenerational Effects on the Adult Heart. AB - Each year millions of pregnant woman are exposed to caffeine, which acts to antagonize adenosine action. The long-term consequences of this exposure on the developing fetus are largely unknown, although in animal models we have found adverse effects on cardiac function. To assess if these effects are transmitted transgenerationally, we exposed pregnant mice to caffeine equivalent to 2-4 cups of coffee at two embryonic stages. Embryos (F1 generation) exposed to caffeine early from embryonic (E) day 6.5-9.5 developed a phenotype similar to dilated cardiomyopathy by 1 year of age. Embryos exposed to caffeine later (E10.5-13.5) were not affected. We next examined the F2 generation and F3 generation of mice exposed to caffeine from E10.5-13.5, as this coincides with germ cell development. These F2 generation adult mice developed a cardiac phenotype similar to hypertrophic cardiomyopathy. The F3 generation exhibited morphological changes in adult hearts, including increased mass. This report shows that in utero caffeine exposure has long-term effects into adulthood and that prenatal caffeine exposure can exert adverse transgenerational effects on adult cardiac function. PMID- 27677357 TI - Scalable loading of a two-dimensional trapped-ion array. AB - Two-dimensional arrays of trapped-ion qubits are attractive platforms for scalable quantum information processing. Sufficiently rapid reloading capable of sustaining a large array, however, remains a significant challenge. Here with the use of a continuous flux of pre-cooled neutral atoms from a remotely located source, we achieve fast loading of a single ion per site while maintaining long trap lifetimes and without disturbing the coherence of an ion quantum bit in an adjacent site. This demonstration satisfies all major criteria necessary for loading and reloading extensive two-dimensional arrays, as will be required for large-scale quantum information processing. Moreover, the already high loading rate can be increased by loading ions in parallel with only a concomitant increase in photo-ionization laser power and no need for additional atomic flux. PMID- 27677358 TI - FAK deletion accelerates liver regeneration after two-thirds partial hepatectomy. AB - : Understanding the molecular mechanisms of liver regeneration is essential to improve the survival rate of patients after surgical resection of large amounts of liver tissue. Focal adhesion kinase (FAK) regulates different cellular functions, including cell survival, proliferation and cell migration. The role of FAK in liver regeneration remains unknown. In this study, we found that Fak is activated and induced during liver regeneration after two-thirds partial hepatectomy (PHx). We used mice with liver-specific deletion of Fak and investigated the role of Fak in liver regeneration in 2/3 PHx model (removal of 2/3 of the liver). We found that specific deletion of Fak accelerates liver regeneration. Fak deletion enhances hepatocyte proliferation prior to day 3 post PHx but attenuates hepatocyte proliferation 3 days after PHx. Moreover, we demonstrated that the deletion of Fak in liver transiently increases EGFR activation by regulating the TNFalpha/HB-EGF axis during liver regeneration. Furthermore, we found more apoptosis in Fak-deficient mouse livers compared to WT mouse livers after PHx. CONCLUSION: Our data suggest that Fak is involved in the process of liver regeneration, and inhibition of FAK may be a promising strategy to accelerate liver regeneration in recipients after liver transplantation. PMID- 27677359 TI - The orientation selectivity of face identification. AB - Recent work demonstrates that human face identification is most efficient when based on horizontal, rather than vertical, image structure. Because it is unclear how this specialization for upright (compared to inverted) face processing emerges in the visual system, the present study aimed to systematically characterize the orientation sensitivity profile for face identification. With upright faces, identification performance in a delayed match-to-sample task was highest for horizontally filtered images and declined sharply with oblique and vertically filtered images. Performance was well described by a Gaussian function with a bandwidth around 25 degrees . Face inversion reshaped this sensitivity profile dramatically, with a downward shift of the entire tuning curve as well as a reduction in the amplitude of the horizontal peak and a doubling in bandwidth. The use of naturalistic outer contours (vs. a common outline mask) was also found to reshape this sensitivity profile by increasing sensitivity to oblique information in the near-horizontal range. Altogether, although face identification is sharply tuned to horizontal angles, both inversion and outline masking can profoundly reshape this orientation sensitivity profile. This combination of image- and observer-driven effects provides an insight into the functional relationship between orientation-selective processes within primary and high-level stages of the human brain. PMID- 27677360 TI - Simulating the Evolution of Functional Brain Networks in Alzheimer's Disease: Exploring Disease Dynamics from the Perspective of Global Activity. AB - Functional brain connectivity is altered during the pathological processes of Alzheimer's disease (AD), but the specific evolutional rules are insufficiently understood. Resting-state functional magnetic resonance imaging indicates that the functional brain networks of individuals with AD tend to be disrupted in hub like nodes, shifting from a small world architecture to a random profile. Here, we proposed a novel evolution model based on computational experiments to simulate the transition of functional brain networks from normal to AD. Specifically, we simulated the rearrangement of edges in a pathological process by a high probability of disconnecting edges between hub-like nodes, and by generating edges between random pair of nodes. Subsequently, four topological properties and a nodal distribution were used to evaluate our model. Compared with random evolution as a null model, our model captured well the topological alteration of functional brain networks during the pathological process. Moreover, we implemented two kinds of network attack to imitate the damage incurred by the brain in AD. Topological changes were better explained by 'hub attacks' than by 'random attacks', indicating the fragility of hubs in individuals with AD. This model clarifies the disruption of functional brain networks in AD, providing a new perspective on topological alterations. PMID- 27677361 TI - Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries. AB - BACKGROUND/OBJECTIVES: The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries. SUBJECTS/METHODS: A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6-13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (+/-95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method. RESULTS: There were no strong associations between prostate cancer risk and 37 dietary factors. CONCLUSIONS: Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men. PMID- 27677362 TI - Choline metabolic pathway gene polymorphisms and risk for Down syndrome: An association study in a population with folate-homocysteine metabolic impairment. AB - BACKGROUND/OBJECTIVES: Choline is an essential nutrient involved in one-carbon metabolism, but its role in mechanisms underlying meiotic non-disjunction is poorly known. The relationship between folate-homocysteine metabolic pathway gene polymorphism and Down syndrome (DS) risk has been widely analyzed, but there are limited reports on its correlation with choline metabolism. In the present case control association study, we investigated the relationship of three single nucleotide polymorphisms (SNPs) (phosphatidylethanolamine N-methyltransferase (PEMT) rs12325817, choline dehydrogenase (CHDH) rs12676 and homocysteine methyltransferase (BHMT) rs3733890) of choline metabolism with risk for DS. SUBJECT/METHODS: Genotyping of 228 mothers of a down syndrome child (DSM) and 200 control mothers (CMs) for all SNPs was performed by PCR coupled with restriction fragment length polymorphism method. RESULTS: A significantly increased risk for BHMT +742AA genotype with an odds ratio of 4.96 (95% confidence interval (CI): 1.66-14.88, P=0.0036) was observed. For PEMT rs12325817 and CHDH rs12676, no significant difference in allelic and genotypic frequencies was observed. In genotypic combination analysis considering PEMT -744GG/CHDH +432GG/BHMT +742GG as the reference combination, PEMT -744GC/CHDH +432GG/BHMT +742GG genotypic combination was significantly higher in DSM compared with that in CMs with an odds ratio of 2.061 (95% CI: 1.10-3.86, P=0.0342). We also observed an epistatic interaction between methylenetetrahydrofolate reductase (MTHFR) rs1801133 and choline metabolic pathway gene variants. CONCLUSIONS: Our findings indicate impaired choline metabolism showing a greater risk for DS, especially in a population associated with homocysteine-folate impairment. Further studies are required to confirm our findings. PMID- 27677363 TI - Sociodemographic disparity in the diet quality transition among Chinese adults from 1991 to 2011. AB - BACKGROUND/OBJECTIVES: This study investigates secular trends in diet quality distribution and related socioeconomic disparity from 1991 to 2011 in the Chinese adult population. SUBJECTS/METHODS: The analysis uses the 1991-2011 China Health and Nutrition Survey data on 13 853 participants (6876 men and 6977 women) aged 18-65 with 56 319 responses. Dietary assessment was carried out over a 3-day period with 24-h recalls combined with a household food inventory. We tailored Alternative Healthy Eating Index 2010 (named as tAHEI) to measure diet quality and performed quantile regression to investigate shifts in tAHEI scores at different percentiles and used mixed-effect linear regression to examine average diet quality trend and potential sociodemographic disparity. RESULTS: The energy adjusted mean tAHEI scores increased from 36.9 (36.7-37.1) points in 1991 to 50.3 (50.1-50.5) in 2011 for men (P<0.001) and from 35.6 (35.4-35.8) to 46.9 (46.7 47.1) for women (P<0.001). The covariate-adjusted score of polyunsaturated fatty acids increased by 6.8 (6.6, 7.0) and 7.0 (6.9, 7.2), and the score of long-chain (omega-3) fats increased by 5.3 (5.2, 5.4) and 5.3 (5.2, 5.5) in men and women, respectively, whereas the cereal fiber and red meat scores decreased slightly. Increasing tAHEI score occurred across the entire distribution, and diet quality transition varied across sociodemographic groups. CONCLUSIONS: Chinese diet quality is far from optimal, with moderate improvement over a 21-year period. Findings suggest that nutritional intervention should give priority to low income, low-urbanized communities and southern provincial adults with low diet quality in China. PMID- 27677364 TI - Contribution of branched-chain amino acids to purine nucleotide cycle: a pilot study. AB - BACKGROUND/OBJECTIVES: Branched-chain amino acids (BCAAs) and purine nucleotide cycle (PNC) are both associated with energy metabolism. The purpose of this study was to explore the influences of BCAA supplementation on the PNC activity of male athletes in response to a bout of endurance running exercise. SUBJECTS/METHODS: Twelve male athletes (20.3+/-1.4 years) participated in the study. Each of the athletes received 12 g of a BCAA supplement (leucine 54%, isoleucine 19% and valine 27%) per day during the study. They performed two identical 60-min running exercises (65-70% maximum heart rate reserved) before and after receiving the BCAA supplements for 15 days. In addition to body composition measurement, plasma and urinary samples were also collected. Plasma samples were examined for the concentrations of glucose, lactate, BCAAs, alanine, glutamine, aspartate, hypoxanthine and uric acid. Urinary samples were examined for the concentrations of urea nitrogen, hydroxyproline, 3-methylhistidine and creatinine. RESULTS: Body composition and the concentrations of urinary metabolites were not affected by BCAA supplementation, whereas clearance of plasma lactate after recovery from exercise was enhanced by BCAA supplementation (P<0.05). Plasma aspartate concentration was increased (P<0.05), whereas plasma glutamine, hypoxanthine and uric acid concentrations were decreased (P<0.05) by BCAA supplementation. CONCLUSIONS: The findings suggest that BCAA supplements not only provided additional substrate to meet the energy demands of the athletes during endurance exercise but also reduced their PNC activity, and subsequently decreased uric acid production and reduced the incidence of gout in a person engaging in endurance exercise. PMID- 27677365 TI - Serum hs-CRP varies with dietary cholesterol, but not dietary fatty acid intake in individuals free of any history of cardiovascular disease. AB - The objective of this study was to investigate whether serum high-sensitivity C reactive protein (hs-CRP) concentration varies with dietary fatty acid intake in Iranian adults free of any history of cardiovascular disease (CVD). This cross sectional study involved 8105 adults (3142 men) aged 35-65 years. Dietary intake was assessed using 24-h dietary recalls. The relationship between anthropometric, cardiometabolic risk factors and dietary data and serum hs-CRP was assessed using SPSS software. Median crude dietary saturated fat decreased across hs-CRP quarters (P =0.009 for linear trend), whereas energy-adjusted total fat (P =0.017), trans-fat (P =0.016), monounsaturated fatty acids (P =0.030) and cholesterol (P =0.005) monotonically increased, with some evidence of statistical interactions by gender. In conclusion, serum hs-CRP concentrations were associated with some components of dietary fatty acid intake in our population of individuals without CVD, suggesting that dietary fat intake could be associated with subclinical inflammation. PMID- 27677367 TI - Adherence to Healthy Eating Index-2010 is inversely associated with metabolic syndrome and its features among Iranian adult women. AB - BACKGROUND/OBJECTIVES: Nowadays, metabolic syndrome (MetS) is deemed as a major public health challenge in both developed and developing countries. Therefore, the aim of this study was to determine the association between Healthy Eating Index-2010 (HEI-2010) score and MetS and its features among Iranian female nurses. SUBJECTS/METHODS: This cross-sectional study was performed among 1036 Iranian women. A validated, self-administered, dish-based, semiquantitative food frequency questionnaire was used to assess the habitual intake of participants. HEI-2010 score was used to assess diet quality of participants. MetS was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Multivariate logistic regression adjusted for potential confounders was used to assess the relation between HEI-2010 and MetS. RESULTS: After adjusting for potential confounders, participants in the highest quartile of HEI-2010 had the lowest risk of MetS compared with those in the first quartile (odds ratio: 0.72; 95% confidence interval: 0.50-0.96). Furthermore, the risk of MetS features including abdominal obesity, high blood pressure, high serum triacylglycerol and low serum high-density lipoprotein-cholesterol significantly decreased across HEI-2010 quartiles (P<0.05). CONCLUSIONS: Higher HEI-2010 scores were inversely associated with lower risk of MetS and its components among Iranian women. PMID- 27677366 TI - Changes in body composition following haemodialysis as assessed by bioimpedance spectroscopy. AB - BACKGROUND/OBJECTIVES: Patients with chronic kidney disease treated by haemodialysis (HD) are at increased risk of sarcopenia. Bioelectrical impedance spectroscopy (BIS) can be used to determine body composition, and is one of the several potential screening tools for sarcopenia. The newer generation of portable hand-held devices can be readily used in dialysis centres. The results from BIS devices using a two-compartmental model of body composition can be affected by hydration status and so ideally measurements should be made when patients are not overhydrated. More recently BIS devices using a three compartmental body model, which separate normally hydrated lean tissues from extracellular water (ECW) excess. We wished to determine whether body composition measured using such a BIS device was affected by hydration status. SUBJECTS/METHODS: We performed BISs pre and post HD using a three-body compartmental model. RESULTS: BISs were recorded in 48 patients; 68.8% male; mean age 67.70+/-14.21 years, weight pre dialysis 70.54+/-18.07, which fell post to 68.58+/-17.78 kg, ECW fell 16.92+/-4.76 vs 15.66+/-4.43 l, P<0.001, whereas there was no change for intracellular water 14.84+/-4.27 vs 14.90+/-4.68 l. Fat-free mass index (FFMI) fell 17.87+/-3.98 vs 16.78+/-3.97 kg/m2, P<0.001, whereas fat mass index (FMI) increased from 7.87+/-3.98 vs 8.12+/-3.81 kg/m2, P=0.002. A fall in FFMI was associated with an increase in FMI (r=0.804, P<0.001). CONCLUSION: FMI and FFMI measured by bioelectrical impedance assessment are both confounded by hydration status. Although pre-dialysis measurements are more convenient, we suggest BIS should preferably be performed post-dialysis when patients are less overhydrated and have less electrolyte imbalances. PMID- 27677368 TI - Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil. AB - BACKGROUND: Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. OBJECTIVES: The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. SUBJECTS/METHODS: As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. RESULTS: Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6 versus 0.7 mg/dl, respectively, P=0.016). CONCLUSIONS: CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk. PMID- 27677369 TI - Ultraviolet radiation and effects on humans: the paradigm of maternal vitamin D production during pregnancy. AB - Current evidence indicates that neonates born of mothers with vitamin D deficiency during pregnancy have greater risk for developing hypocalcemia, rickets and extra-skeletal disorders. Despite the classic knowledge that ultraviolet-B (UVB) exposure is the most efficient way for a future mother to obtain optimal vitamin D concentrations, no current consensus or clinical recommendations exist regarding the duration and timing of UVB exposure for pregnant women. This article offers a narrative review of available data regarding how UVB exposure affects maternal vitamin D production during pregnancy, along with a discourse on clinical implications of this public health issue. Future studies would benefit from adopting UVB exposure estimates to recommend appropriate UVB exposure to pregnant women. Doing so could provide a more holistic and practical approach in managing maternal hypovitaminosis D during pregnancy. PMID- 27677371 TI - The nutritional quality of foods carrying health-related claims in Germany, The Netherlands, Spain, Slovenia and the United Kingdom. PMID- 27677370 TI - Aging, low-grade systemic inflammation and vitamin D: a mini-review. AB - We conducted a mini-review of the literature, focusing on aging-related systemic inflammation and its association with vitamin D (VitD). As main findings, data indicate that inflammation in aging seems to have multiple origins, including immunosenescence, and from intestinal and adipose tissue, where VitD may modulate these three factors, through mechanisms not totally known. From the selected studies, three randomized clinical trials of VitD supplementation showed improvements in inflammatory status, whereas two studies did not. Ten epidemiological studies showed associations between VitD and inflammation, whereas two studies did not. One case study reinforced this association. As such, we can assume a reasonable association between VitD and inflammation in the elderly, and a promising role of supplementation in some situations. However, most studies did not take into account environmental and individual factors such as the season of the year, latitude, skin color or even the use of some medicines; in addition, the doses, time of intervention and the sample sizes differed between the studies. In conclusion, although more controlled VitD studies, both clinical and epidemiological, are necessary, it is important to remember the network of factors involved in systemic inflammation in the elderly; an understanding of the dietetic and non-dietetic factors is needed to offer a realistic approach. PMID- 27677372 TI - Semiconductor Polymer/Top Electrode Interface Generated by Two Deposition Methods and Its Influence on Organic Solar Cell Performance. AB - In this Research Article, the effect of two techniques for top-electrode deposition in organic photovoltaics (OPVs) cells with the configuration ITO/PEDOT:PSS/PTB7-Th:PC71BM/PFN/top-electrode is analyzed. One deposition was made by evaporation under high vacuum, meanwhile the other was carried out at normal room atmosphere; for the former, a double layer of Ca and the eutectic alloy Field's metal (FM) was thermally evaporated, while for the latter FM was deposited just by melting and dropping it on top of the delimited active area at temperatures about 90 degrees C. The average short-circuit photocurrent density, open circuit voltage and fill factor for devices with either Ca/FM (evaporated) or FM (by dripping) cathode, were very similar: around 13.20 mA/cm2, 840 mV, and 0.6, respectively. Average efficiency for devices with the mentioned evaporated cathode was of 6.4% (largest value 7.0%), meanwhile for devices with the cathode deposited by dripping, it was of 6.1% (largest value 6.5%). Morphological analysis, by atomic force microscopy on the surface of a FM electrode, detached from an OPV device, shows inhomogeneities and pinholes in its surface with an average roughness of 16 nm. OPV photocurrent was studied by means of laser beam induced current (LBIC), it showed that OPVs devices with FM top electrode exhibits an inhomogeneous response. An impedance analysis was also carried out and results were correlated with defects observed at the studied interface. In spite of the mentioned deficiencies at FM interface, overall PV performance of devices with this electrode highlights the convenience of using FM because of its easy, fast, and low-cost deposition (vacuum free) characteristics. PMID- 27677373 TI - The AAA+ FtsH Protease Degrades an ssrA-Tagged Model Protein in the Inner Membrane of Escherichia coli. AB - In eubacteria, the tmRNA system frees ribosomes that stall during protein synthesis and adds an ssrA tag to the incompletely translated polypeptide to target it for degradation. The AAA+ ClpXP protease degrades most ssrA-tagged proteins in the Escherichia coli cytoplasm and was recently shown to degrade an ssrA-tagged protein in the inner membrane. However, we find that tmRNA-mediated tagging of E. coli ProW1-182, a different inner-membrane protein, results in degradation by the membrane-tethered AAA+ FtsH protease. ClpXP played no role in the degradation of ProW1-182 in vivo. These studies suggest that a complex distribution of proteolytic labor maintains protein quality control in the inner membrane. PMID- 27677374 TI - Early unpredictability predicts increased adolescent externalizing behaviors and substance use: A life history perspective-CORRIGENDUM. PMID- 27677375 TI - The influence of geographical location, host maturity and sex on intestinal helminth communities of the double-crested cormorant Phalacrocorax auritus from the eastern United States. AB - Here the intestinal helminth infracommunities of 218 double-crested cormorants (Phalacrocorax auritus) from 11 locations in Alabama, Minnesota, Mississippi and Vermont are documented. Trematode infections were present in 98% of hosts; 65% of cormorants carried cestode infections, 4% were infected with acanthocephalans and 66% had nematode intestinal parasites. Parasite infracommunities of hosts collected on wintering grounds had higher richness and diversity than did birds collected on breeding grounds. Differences in parasite richness and diversity between male and female P. auritus were also detected, but not between immature and mature bird hosts. Parasite intensity did not differ by sex, maturity, or between breeding and wintering season. The most common parasite was Drepanocephalus auritus (spathans), which is recognized as a disease agent that negatively impacts the catfish aquaculture industry in the US. Echinochasmus sp. in double-crested cormorants is documented for the first time in the United States. We suggest that the differences observed among parasite infracommunities could be associated with the foraging distances travelled by P. auritus during breeding and wintering seasons, which is limited by allocation of parental care during the breeding season. PMID- 27677377 TI - An evaluation of pre-hospital emergency medical systems for suspected ST elevation myocardial infarction in Colorado. AB - OBJECTIVES: Patients presenting with ST-elevation myocardial infarction (STEMI) benefit from rapid cardiac reperfusion therapy. Emergency medical service (EMS) agencies can improve patient outcomes by calling STEMI alerts to the receiving facility. The aim of this study was to evaluate the use of pre-hospital activation systems for suspected ST-elevation myocardial infarctions (STEMI) throughout Colorado. METHODS: A cross sectional, survey design was utilized to collect all data from EMS agencies in Colorado. A univariable logistic regression model was used to identify factors predictive of an agency reporting that they utilize a STEMI activation protocol. RESULTS: 84.5% [95% CI: 78.3 to 90.7%] of agencies included indicate that they utilize a STEMI activation protocol. Based on the logistic regression analysis, the number of EMT employees was significantly associated with whether or not an agency indicates that they utilize a STEMI activation protocol. For every 10% increase in the number of EMTs employed by an EMS agency, there was a 3.0 [95% CI: 1.5 to 6.0, p = 0.0012] fold increase in the odds of the agency indicating they utilize a STEMI activation protocol. CONCLUSIONS: Our study provides evidence that larger agencies are more likely to utilize a STEMI activation protocol. In areas without a STEMI system of care, improvements in smaller agencies that cover more ground (with longer transport times) should be the focus for protocol implementation. Based on the current prevalence of such training, competency based training in reading ST elevations on ECG should be considered by EMS agencies. PMID- 27677376 TI - Dexmedetomidine protects against glucocorticoid induced progenitor cell apoptosis in neonatal mouse cerebellum. AB - OBJECTIVES: Glucocorticoids (GCs) are used to improve respiratory mechanics in preterm infants despite clinical evidence linking neonatal GC therapy to cerebellar pathology. In developing mouse cerebellum, the GC dexamethasone (DEX) causes rapid GC-induced neural progenitor cell apoptosis (GINA). Focusing on pharmacological neuroprotection strategies, we investigated whether dexmedetomidine (DMT) protects against GINA. METHODS: Neonatal mice were pretreated with DMT prior to DEX challenge. Additionally, we tested clonidine and yohimbine in vivo to determine mechanism of DMT neuroprotection. For in vitro studies, cerebellar neural progenitor cells were pretreated with DMT before DEX challenge. RESULTS: In vivo, DMT attenuated GINA at 1 MUg/kg and above, p < 0.0001. Clonidine significantly attenuated GINA, p < 0.0001, while yohimbine reversed DMT neuroprotection, p < 0.0001, suggesting DMT neuroprotection is likely mediated via adrenergic signaling. In vitro, DMT neuroprotection was achieved at 10 MUM and above, p < 0.001, indicating DMT rescue is cell autonomous. CONCLUSIONS: DMT affords dose-dependent neuroprotection from GINA at clinically relevant doses, an effect that is cell autonomous and likely mediated by alpha2 adrenergic receptor agonism. DMT co-administration with GCs may be an effective strategy to protect the neonatal brain from GINA while retaining the beneficial effects of GCs on respiratory mechanics. PMID- 27677379 TI - Aetiology of PCR negative suspected Crimean-Congo hemorrhagic fever cases in an endemic area. AB - Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal tick-borne viral infection that is widely distributed worldwide. The diagnosis is frequently missed due to the non-specific initial symptoms and the differential diagnosis included many infectious and non-infectious causes. This retrospective study describes the clinical features and final diagnoses of 116 suspect CCHF cases that were admitted to a tertiary CCHF center in Turkey, and were CCHF IgM and PCR negative. PMID- 27677380 TI - Context matters! The relationship between mother-reported family nutrition climate, general parenting, food parenting practices and children's BMI. AB - BACKGROUND: Efforts to explain children's nutrition behavior or weight often involve investigating the parent-child relationship, typically studying the associations between food parenting practices (FPPs) and child outcomes. However, these behaviors are embedded in a broader system: general parenting (GP, the general emotional climate at home), and the family health climate (an aspect of the broader family system in the context of health). In the current study, we combined the parent-child measures of parenting (FPPs and GP) and the nutritional dimension of the family health climate (family nutrition climate, FNC) to get a broader view of how these concepts are interrelated. The current study had two aims: predicting FPPs using GP and FNC as predictor variables, and investigating the relationship between FPPs and children's weight in different groups of parents, based on low and high GP and FNC scores. METHODS: We collected cross sectional data via an online survey panel. Mothers of 267 children aged 5-12 years filled out a questionnaire assessing demographics (e.g., children's weight and height), GP, FPPs, and FNC. Bivariate correlation coefficients were calculated between all constructs. Structural equation modeling was performed to test the hypothesized relationships between GP, FNC and FPPs. Hereafter, different groups of parents were identified, using median split, based on a low or high score on GP or a low or high score on FNC. Bivariate correlation coefficients were calculated between FPPs and children's BMI z-score for these different groups. RESULTS: GP and FNC were consistently positively correlated (all r's >=.177), and both concepts were positively associated with healthy FPPs (all r's >=.214). In families with a positive context (i.e. scoring high on GP and on FNC), healthy FPPs were associated with lower BMI z-scores of the children (r -.229). This association was not found for children with a more negative family context. CONCLUSIONS: FNC and GP are valuable additional concepts to investigate relationships between FPPs and child outcomes. We recommend that more studies, next to investigating the parent-child system, include a measure of the broader family system, in order to get a broader view of the mechanisms explaining child health behaviors and weight status. PMID- 27677378 TI - Advancing vector biology research: a community survey for future directions, research applications and infrastructure requirements. AB - Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector-pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations. PMID- 27677381 TI - Prevalence and risk factors for asthma among children aged 0-14 years in Hangzhou: a cross-sectional survey. AB - BACKGROUND: Asthma is a global problem. Prevalence varies among different countries and cities. We aimed to obtain the prevalence, describe the characteristics, and discover factors that may relate to asthma in Hangzhou. METHODS: This cross-sectional study was conducted in Hangzhou. The subjects were children aged 14 years and younger. A control group of non-asthma children that matched in age and sex with each asthmatic patient was also randomly selected and interviewed. International Study of Asthma and Allergies in Childhood and National Epidemiology study of Asthma and Allergies in China questionnaires were used in this survey. RESULTS: We have questionnaired 13,877 children, and 665 (4.8 %) children were diagnosed asthma. The guardians regarded the cost of asthma management affordable in 49.4 %, tolerable in 46.9 %, and intolerable in 3.7 %. Both guardians and children have been absent from work or school due to children's asthma. Respiratory tract infection was the most common trigger of asthma attacks (85.1 %). Other common causes included cold air, house dust, exercise, fish and shrimp, pollen, and et al. Interestingly, we also found in children 6 years and older, some triggers happened more than that in children 5 years and younger. Those factors included exercise, emotional changes, house dust, pollen, renovation works in the home, mosquito-repellent incense and pets (all the p values were <0.05). We compared some factors may relate to asthma development. Higher percentage of family history of asthma, personal history of allergy (atopic dermatitis, drug allergy and food allergy), comorbidities (allergic rhinitis, sinusitis, adenoidal hypertrophy, and urticaria), caesarean birth and complications ever happened during pregnancy were discovered in asthma children than in non-asthma children (all the p values were <0.05). Exclusive breastfeeding within first 6 months and keeping animals had higher percentage in non-asthma children than in asthma (both the p values were <0.05). Inhaled corticosteroid (ICS)/ICS + long-acting beta2 agonists (LABA) was applied to 46.2 % of patients. Traditional Chinese medicine (TCM) was used in 44.2 % of asthma children, while leukotriene receptor antagonist (LTRA) was used in 36.4 % of them. The adherence scored higher in TCM than in ICS/ICS + LABA (P = 0.003) and LTRA. CONCLUSIONS: In conclusion, we conducted an epidemiology study in Hangzhou. The prevalence of childhood asthma was 4.8 %. Asthma was an economic and social burden to both children and guardians. Risk factors of asthma development may include caesarean birth, personal history of allergy and concomitant allergic diseases. Exclusive breastfeeding within first 6 months and keeping animals might be protecting factors. TCM was really popular in China besides ICS/ICS + LABA and LTRA. PMID- 27677382 TI - Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial. AB - BACKGROUND: GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include 'G' and 'liquid ecstasy'. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to 'come down' after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency/intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day 'preload' prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further. METHODS/DESIGN: This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL-dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2 day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness. DISCUSSION: This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal. TRIAL REGISTRATION: ISRCTN59911189 . Registered 14 October 2015. PROTOCOL: v3.1, 1 February 2016. PMID- 27677383 TI - Vasopressors and inotropes in cardiogenic shock: is there room for "adrenaline resuscitation"? PMID- 27677384 TI - Interactions between peroxiredoxin 2, hemichrome and the erythrocyte membrane. AB - Peroxiredoxin 2 (Prx2) is an abundant antioxidant protein in erythrocytes that protects against hemolytic anemia resulting from hemoglobin oxidation and Heinz body formation. A small fraction of Prx2 is bound to the cell membrane, but the mechanism and relevance of binding are not clear. We have investigated Prx2 interactions with the erythrocyte membrane and oxidized hemoglobin and whether these interactions are dependent on Prx2 redox state. Membrane binding of Prx2 in erythrocytes decreased when the cells were treated with H2O2, but studies with purified Prx2 and isolated ghosts showed that the interaction was independent of Prx2 redox state. Hemoglobin oxidation leads to the formation of hemichrome, a denatured form of the protein that binds to Band3 protein in the cell membrane as part of the senescence process and is a precursor of Heinz bodies. Hemichrome competed with Prx2 and decreased Prx2 binding to the membrane, potentially explaining the decreased binding in oxidant-exposed cells. The increased membrane binding of Prx2 seen with increasing intracellular calcium was less sensitive to H2O2 or hemichrome, suggesting an alternative mode of binding. Prx2 was also shown to exhibit chaperone-like activity by retarding the precipitation of pre formed hemichrome. Our results suggest that Prx2, by restricting membrane binding of hemichrome, could impede Band3 clustering and exposure of senescence antigens. This mechanism, plus the observed chaperone activity for oxidized hemoglobin, may help protect against hemolytic anemia. PMID- 27677385 TI - Albiglutide: a unique GLP-1 receptor agonist. AB - INTRODUCTION: Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection. Area covered: The pharmacokinetic and pharmacodynamic properties of albiglutide and its clinical effects are discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administration approval documents. Expert opinion: Albiglutide has a chemical structure quite distinct from that of other marketed GLP-1 RAs. The agent has less gastrointestinal side effects than other comparable GLP-1 RAs and is safe in patients with renal failure. As a sole treatment for diabetes and used with other hypoglycemic agents, it achieves a lowering of HbA1c of up to 1%, less than several competitor GLP-1 RAs. The benefit on weight reduction is minimal compared to other GLP-1 RAs. There exists concern about an imbalance of pancreatitis cases in the approval program as well as injection site reactions which led to discontinuance of therapy in up to 2% of participants. A large long term study now underway will determine if albiglutide, with its lower level of GI intolerance, has a place in the treatment of patients with increased risk of cardiovascular events. PMID- 27677386 TI - Human innate lymphoid cells. AB - Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-gamma mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. PMID- 27677387 TI - Prognostic Value of the Thrombolysis in Myocardial Infarction Risk Score in ST Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction (from the EPHESUS Trial). AB - The Thrombolysis in Myocardial Infarction (TIMI) risk score remains a robust prediction tool for short-term and midterm outcome in the patients with ST elevation myocardial infarction (STEMI). However, the validity of this risk score in patients with STEMI with reduced left ventricular ejection fraction (LVEF) remains unclear. A total of 2,854 patients with STEMI with early coronary revascularization participating in the randomized EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial were analyzed. TIMI risk score was calculated at baseline, and its predictive value was evaluated using C-indexes from Cox models. The increase in reclassification of other variables in addition to TIMI score was assessed using the net reclassification index. TIMI risk score had a poor predictive accuracy for all cause mortality (C-index values at 30 days and 1 year <=0.67) and recurrent myocardial infarction (MI; C-index values <=0.60). Among TIMI score items, diabetes/hypertension/angina, heart rate >100 beats/min, and systolic blood pressure <100 mm Hg were inconsistently associated with survival, whereas none of the TIMI score items, aside from age, were significantly associated with MI recurrence. Using a constructed predictive model, lower LVEF, lower estimated glomerular filtration rate (eGFR), and previous MI were significantly associated with all-cause mortality. The predictive accuracy of this model, which included LVEF and eGFR, was fair for both 30-day and 1-year all-cause mortality (C-index values ranging from 0.71 to 0.75). In conclusion, TIMI risk score demonstrates poor discrimination in predicting mortality or recurrent MI in patients with STEMI with reduced LVEF. LVEF and eGFR are major factors that should not be ignored by predictive risk scores in this population. PMID- 27677388 TI - Etiologies and Predictors of 30-Day Readmission and In-Hospital Mortality During Primary and Readmission After Transcatheter Aortic Valve Implantation. AB - There are sparse data on the etiologies and predictors of readmission after transcatheter aortic valve implantation (TAVI). The study cohort was derived from the National Readmission Data 2013, a subset of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. TAVI was identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. The coprimary outcomes were 30-day readmissions and in-hospital mortality during primary admission and readmission. Hierarchical 2-level logistic models were used to evaluate study outcomes. Our analysis included 5,702 (weighted n = 12,703) TAVI procedures. About 1,215 patients were readmitted (weighted n = 2,757) within 30 days during the study year. Significant predictors of readmission included transapical access (OR, 95% CI, p value) (1.23, 1.10 to 1.38, <0.01), diabetes (1.18, 1.06 to 1.32, p 0.004), chronic lung disease (1.32, 1.18 to 1.47, <0.01), renal failure (1.43, 1.24 to 1.65, <0.01), patients discharged to facilities (1.28, 1.14 to 1.43, <0.01), and those who had lengthier hospital stays during primary admission (length of stay >10 days: 3.06, 2.22 to 4.22, <0.01). Female gender (1.39, 1.16 to 1.68, <0.01), blood transfusion (1.88, 1.55 to 2.29, <0.01), use of vasopressors (3.63, 2.50 to 5.28, <0.01), hemodynamic support (6.39, 5.20 to 7.85, <0.01) and percutaneous coronary intervention (1.89, 1.30 to 2.74, 0.01) during primary admission were significant predictors of in-hospital mortality. Age and transapical access were significant predictors of in-hospital mortality during readmission. In conclusion, heart failure, pneumonia, and bleeding complications are among important etiologies of readmission in patients after TAVI. Patients who underwent transapical TAVI and those with slower in-hospital recovery and co morbidities such as chronic lung disease and renal failure are more likely to be readmitted to the hospital. PMID- 27677389 TI - The potential use of low-frequency tones to locate regions of outer hair cell loss. AB - Current methods used to diagnose cochlear hearing loss are limited in their ability to determine the location and extent of anatomical damage to various cochlear structures. In previous experiments, we have used the electrical potential recorded at the round window -the cochlear response (CR) -to predict the location of damage to outer hair cells in the gerbil. In a follow-up experiment, we applied 10 mM ouabain to the round window niche to reduce neural activity in order to quantify the neural contribution to the CR. We concluded that a significant proportion of the CR to a 762 Hz tone originated from phase locking activity of basal auditory nerve fibers, which could have contaminated our conclusions regarding outer hair cell health. However, at such high concentrations, ouabain may have also affected the responses from outer hair cells, exaggerating the effect we attributed to the auditory nerve. In this study, we lowered the concentration of ouabain to 1 mM and determined the physiologic effects on outer hair cells using distortion-product otoacoustic emissions. As well as quantifying the effects of 1 mM ouabain on the auditory nerve and outer hair cells, we attempted to reduce the neural contribution to the CR by using near-infrasonic stimulus frequencies of 45 and 85 Hz, and hypothesized that these low-frequency stimuli would generate a cumulative amplitude function (CAF) that could reflect damage to hair cells in the apex more accurately than the 762 stimuli. One hour after application of 1 mM ouabain, CR amplitudes significantly increased, but remained unchanged in the presence of high-pass filtered noise conditions, suggesting that basal auditory nerve fibers have a limited contribution to the CR at such low frequencies. PMID- 27677390 TI - Shipping noise in a dynamic sea: a case study of grey seals in the Celtic Sea. AB - Shipping noise is a threat to marine wildlife. Grey seals are benthic foragers, and thus experience acoustic noise throughout the water column, which makes them a good model species for a case study of the potential impacts of shipping noise. We used ship track data from the Celtic Sea, seal track data and a coupled ocean acoustic modelling system to assess the noise exposure of grey seals along their tracks. It was found that the animals experience step changes in sound levels up to ~20dB at a frequency of 125Hz, and ~10dB on average over 10-1000Hz when they dive through the thermocline, particularly during summer. Our results showed large seasonal differences in the noise level experienced by the seals. These results reveal the actual noise exposure by the animals and could help in marine spatial planning. PMID- 27677391 TI - Host condition and accumulation of metals by acanthocephalan parasite Echinorhynchus gadi in cod Gadus morhua from the southern Baltic Sea. AB - In this study, we analyzed the relationship between concentration of metals in the host-parasite system (cod - acanthocephalan Echinorhynchus gadi) and Fulton's condition factor (FCF) of the host. The relationship between metal (Ca, Cd, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Pb, Sr, Zn) concentrations in E. gadi and cod tissues was expressed as a bioconcentration factor (BCF), the ratio of the concentration in the parasite tissue to that in host tissues. Acanthocephalans accumulated mainly toxic metals (Cd, Pb), as well as Sr, Ca, Na. Cadmium showed the highest bioconcentration in parasites (BCF >200) compared to fish muscle. Significant negative correlation was detected between FCF and the concentration of Cd and Hg in cod liver. In contrast, FCF was positively correlated with the concentration of Hg in acanthocephalan tissues. PMID- 27677392 TI - Estrogenic compound profiles in an urbanized industry-impacted coastal bay and potential risk assessment by pollution indices and multivariative statistical methods. AB - The occurrence and distribution of target estrogenic compounds in a highly urbanized industry-impacted coastal bay were investigated, and contamination profiles were evaluated by estimating total estradiol equivalents (?EEQs) and risk quotients (RQs). Phenolic compounds were the most abundant xenoestrogens, but seldom showed contribution to the ?EEQs. The diethylstilbestrol (DES) and 17alpha-ethinylestradiol (EE2) were the major contributors followed by 17beta estradiol (E2) in comparison with a slight contribution from estrone (E1) and estriol (E3). Both ?EEQs and RQs indicated likely adverse effects posed on resident organisms. Further, multivariate statistical method comprehensively revealed pollution status by visualized factor scores and identified multiple "hotspots" of estrogenic sources, demonstrating the presence of complex pollution risk gradients inside and particularly outside of bay area. Overall, this study favors the integrative utilization of pollution indices and factor analysis as powerful tool to scientifically diagnose the pollution characterization of human derived chemicals for better management decisions in aquatic environments. PMID- 27677393 TI - Assessing the footprint and volume of oil deposited in deep-sea sediments following the Deepwater Horizon oil spill. AB - The lateral and vertical extents of Macondo oil in deep-sea sediments resulting from the 2010 Deepwater Horizon oil spill were determined using chemical forensics and geostatistical kriging of data from 2397 sediment samples from 875 cores collected in 2010/2011 and 2014. The total mass of Macondo-derived hopane on the seafloor in 2010/2011 was conservatively estimated between 2.00 and 2.26metric tons, derived from 219,000 to 247,000barrels of oil; or 6.9 to 7.7% of the 3.19millionbarrels spilled. Macondo-derived hopane was deposited over 1030 to 1910km2 of the seafloor, mostly (>97%) in surface (0-1cm) and near-surface (1 3cm) sediments, which is consistent with short-term oil deposition. Although Macondo oil was still present in surface sediments in 2014, the total mass of Macondo-derived hopane was significantly lower (~80 to 90%) than in 2010/2011, affirming an acute impact from the spill and not long-term deposition from natural seeps. PMID- 27677394 TI - New directions for pharmacotherapy in the treatment of acute coronary syndrome. AB - INTRODUCTION: Acute coronary syndromes (ACS) are one of the leading causes of death worldwide. Several landmark trials, followed by a widespread introduction of new agents, have significantly improved ACS outcomes in recent years. However, despite the use of contemporary therapy, a substantial number of ACS patients continue to suffer from cardiovascular events. Areas covered: The aim of this review was to summarize available data on innovative drugs and pharmacological strategies that have potential to amend the current ACS therapy. We present the results of recent large clinical trials, as well as insights from ongoing phase III and phase IV studies, exploring the value of new strategies for the improvement of outcomes in ACS. Expert opinion: More potent platelet inhibition, more profound lipid reduction and possibly anti-inflammatory action are considered to have potential to further reduce the rates of adverse cardiovascular and thrombotic events in ACS patients. 'Hit fast, hit hard' approach regarding novel antiplatelet and lipid-lowering therapy seems attractive, but it has to be considered that these strategies may be associated with increased adverse events rate. Introduction of cangrelor and ezetimibe, and potentially future recognition of proprotein convertase subtilisin/kexin type 9 antibodies, are likely to alter the landscape of ACS pharmacotherapy. PMID- 27677395 TI - Developing a predictive risk model for first-line antiretroviral therapy failure in South Africa. AB - INTRODUCTION: A substantial number of patients with HIV in South Africa have failed first-line antiretroviral therapy (ART). Although individual predictors of first-line ART failure have been identified, few studies in resource-limited settings have been large enough for predictive modelling. Understanding the absolute risk of first-line failure is useful for patient monitoring and for effectively targeting limited resources for second-line ART. We developed a predictive model to identify patients at the greatest risk of virologic failure on first-line ART, and to estimate the proportion of patients needing second-line ART over five years on treatment. METHODS: A cohort of patients aged >=18 years from nine South African HIV clinics on first-line ART for at least six months were included. Viral load measurements and baseline predictors were obtained from medical records. We used stepwise selection of predictors in accelerated failure time models to predict virologic failure on first-line ART (two consecutive viral load levels >1000 copies/mL). Multiple imputations were used to assign missing baseline variables. The final model was selected using internal-external cross validation maximizing model calibration at five years on ART, and model discrimination, measured using Harrell's C-statistic. Model covariates were used to create a predictive score for risk group of ART failure. RESULTS: A total of 72,181 patients were included in the analysis, with an average of 21.5 months (IQR: 8.8-41.5) of follow-up time on first-line ART. The final predictive model had a Weibull distribution and the final predictors of virologic failure were men of all ages, young women, nevirapine use in first-line regimen, low baseline CD4 count, high mean corpuscular volume, low haemoglobin, history of TB and missed visits during the first six months on ART. About 24.4% of patients in the highest quintile and 9.4% of patients in the lowest quintile of risk were predicted to experience treatment failure over five years on ART. CONCLUSIONS: Age, sex, CD4 count and having any missed visits during the first six months on ART were the strongest predictors of ART failure. The predictive model identified patients at high risk of failure, and the predicted failure rates over five years closely reflected actual rates of failure. PMID- 27677396 TI - Quantitative PCR and unconventional serological methods to evaluate clomipramine treatment effectiveness in experimental Trypanosoma cruzi infection. AB - Clomipramine (CLO), a tricyclic antidepressant drug, has been used for the treatment of mice infected with Trypanosoma cruzi. In this work we evaluated the effectiveness of CLO treatment upon T. cruzi-infected mice in the chronic phase of the experimental infection using Quantitative polymerase chain reaction (qPCR) and recombinant ELISA. Sixty Swiss albino mice were inoculated with 50 trypomastigote forms of T. cruzi (Tulahuen strain). CLO treatment consisted of 5mg/kg/day during 60days by intraperitoneal injection, beginning on day 90 post infection (p.i) when the mice presented electrocardiographic (ECG) alterations compatible with the chronic phase of the disease. The evolution of experimental infection and the treatment efficacy were studied through survival, electrocardiography, serology using a mixture and individual (1, 2, 13, 30, 36 and SAPA) recombinant proteins from epimastigotes and trypomastigotes of T. cruzi; and qPCR on days 180 and 270 p.i. CLO treatment in the chronic phase decreased the parasite load, reduced the levels of antibodies against antigen 13 throughout 270days p.i and reversed the ECG abnormalities in the treated animals, from 100% of the mice with alterations at the beginning of the treatment to only 20% of the mice with alterations by day 270 p.i. This study shows that qPCR and the use of recombinant antigens are more sensitive to evaluate the effectiveness of the treatment and proves that clomipramine may be considered as a new chemotherapy for the chronic phase of the disease. PMID- 27677397 TI - Robust upward dispersion of the neutron spin resonance in the heavy fermion superconductor Ce1-xYbxCoIn5. AB - The neutron spin resonance is a collective magnetic excitation that appears in the unconventional copper oxide, iron pnictide and heavy fermion superconductors. Although the resonance is commonly associated with a spin-exciton due to the d(s+/-)-wave symmetry of the superconducting order parameter, it has also been proposed to be a magnon-like excitation appearing in the superconducting state. Here we use inelastic neutron scattering to demonstrate that the resonance in the heavy fermion superconductor Ce1-xYbxCoIn5 with x=0, 0.05 and 0.3 has a ring-like upward dispersion that is robust against Yb-doping. By comparing our experimental data with a random phase approximation calculation using the electronic structure and the momentum dependence of the -wave superconducting gap determined from scanning tunnelling microscopy (STM) for CeCoIn5, we conclude that the robust upward-dispersing resonance mode in Ce1-xYbxCoIn5 is inconsistent with the downward dispersion predicted within the spin-exciton scenario. PMID- 27677398 TI - Moorean and Tahitian Partula tree snail survival after a mass extinction: New genomic insights using museum specimens. AB - Natural history museum collections provide a biodiversity window into the past and are of particular importance to the study of extinction-impacted clades such as the Pacific Island tree snail family Partulidae. Deliberate introduction of the predatory rosy wolf snail Euglandina rosea in the late 20th century led to the extinction/extirpation of 55/61 Society Island Partulidae species. In this study, we phylogenomically investigated the inter-relationships of the three surviving Society Island valley Partula species: P. taeniata (Moorea), P. clara and P. hyalina (Tahiti). All three formed a distinct clade in earlier mitochondrial phylogenies. Using Next Generation Sequencing (NGS) double digested Restriction Associated DNA sequencing (ddRADseq), we found that 46-year-old lyophilized museum specimens produced similar numbers of reads, sequencing depth, and loci as 10-year old ethanol-preserved collections. Phylogenomic trees indicated that Tahitian P. clara and P. hyalina are the result of a single founding lineage from Moorea, contrasting previous mitochondrial results and clarifying the enigmatic taxonomic status of P. c. incrassa. Our study highlights the utility and viability of NGS techniques for museum specimens and their increased resolution of evolutionary patterns. Sampling will be expanded to include the remaining Society Island partulid taxa to further explore the evolutionary history of this radiation. PMID- 27677399 TI - The origin and phylogenetic relationships of the New Zealand ravens. AB - The relationships of the extinct New Zealand ravens (Corvus spp.) are poorly understood. We sequenced the mitogenomes of the two currently recognised species and found they were sister-taxa to a clade comprising the Australian raven, little raven, and forest raven (C.coronoides, C. mellori and C. tasmanicus respectively). The divergence between the New Zealand ravens and Australian raven clade occurred in the latest Pliocene, which coincides with the onset of glacial deforestation. We also found that the divergence between the two putative New Zealand species C. antipodum and C. moriorum probably occurred in the late Pleistocene making their separation as species untenable. Consequently, we consider Corax antipodum (Forbes, 1893) to be a subspecies of Corvus moriorum Forbes, 1892. We re-examine the osteological evidence that led 19th century researchers to assign the New Zealand taxa to a separate genus, and re-assess these features in light of our new phylogenetic hypotheses. Like previous researchers, we conclude that the morphology of the palate of C. moriorum is unique among the genus Corvus, and suggest this may be an adaptation for a specialist diet. PMID- 27677400 TI - Spin-dependent manipulating of vector beams by tailoring polarization. AB - We examine the spin-dependent manipulating of vector beams by tailoring the inhomogeneous polarization. The spin-dependent manipulating is attributed to the spin-dependent phase gradient in vector beams, which can be regarded as the intrinsic feature of inhomogeneous polarization. The desired polarization can be obtained by establishing the relationship between the local orientation of polarization and the local orientation of the optical axis of waveplate. We demonstrate that the spin-dependent manipulating with arbitrary intensity patterns can be achieved by tailoring the inhomogeneous polarization. PMID- 27677401 TI - The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes. AB - Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I. Rad51 depleted oocytes showed chromosome misalignment and failures in spindle aggregation, affecting the completion of cytokinesis. We found that Rad51 depletion was accompanied by decreased ATP production and mitochondrial membrane potential and increased DNA degradation. We further demonstrated that the mitochondrial defect activated autophagy in Rad51-depleted oocytes. Taken together, we concluded that Rad51 functions to safeguard mitochondrial integrity during the meiotic maturation of oocytes. PMID- 27677402 TI - FAIM2, as a novel diagnostic maker and a potential therapeutic target for small cell lung cancer and atypical carcinoid. AB - Lung neuroendocrine (NE) tumors are a heterogeneous group of tumors arising from neuroendocrine cells that includes typical carcinoid, atypical carcinoid, small cell lung cancer (SCLC), and large cell NE cancer. The subtyping of NE tumors is based on the number of mitoses per high powered field and the presences of necrosis. However, the best diagnostic criteria to differentiate various subtypes of lung NE tumors remains controversial and few diagnostic markers distinguish typical and atypical carcinoid. In this study, we show that FAIM2, an inhibitory molecule in the Fas-apoptosis pathway, is significantly overexpressed in SCLC compared to non-small cell lung cancer. In addition, FAIM2 expression is significantly higher in atypical carcinoid than typical carcinoid. As atypical carcinoid has been shown to have worse clinical outcomes than typical carcinoid, our data suggests that FAIM2 may be a useful diagnostic marker for atypical carcinoid. Knockdown of FAIM2 expression increases Fas-induced apoptotic cell death in SCLC cells. Etoposide treatment combined with FAIM2 inhibition also shows modest but significant reduction of viable SCLC cells. Taken together, our results suggest that FAIM2 is a potential NE tumor marker with higher expression in atypical carcinoid and SCLC, and could be a new therapeutic target for SCLC. PMID- 27677403 TI - Influence of symmetry breaking degrees on surface plasmon polaritons propagation in branched silver nanowire waveguides. AB - Surface plasmon polaritons (SPPs)-based nanowire (NW) waveguides demonstrate promising potentials in the integrated nanophotonic circuits and devices. The realization of controlling SPPs propagation in NWs is significant for the performance of nanophotonic devices when employed for special function. In this work, we report the effect of symmetry breaking degrees on SPPs propagation behavior in manually fabricated branched silver NW structures. The symmetry breaking degree can be tuned by the angle between main NW and branch NW, which influences the emissions at the junction and the main NW terminal in a large extent. Our results illustrate the significance of symmetry breaking degree on SPPs propagation in NW-based waveguides which is crucial for designing the future nanophotonic circuits. PMID- 27677404 TI - Modelling responses of the inert-gas washout and MRI to bronchoconstriction. AB - Many lung diseases lead to an increase in ventilation heterogeneity (VH). Two clinical practices for the measurement of patient VH are in vivo imaging, and the inert gas multiple breath washout (MBW). In this study computational modelling was used to compare the responses of MBW indices LCI and scond and MRI measured global and local ventilation indices, sigmar and sigmalocal, to constriction of airways in the conducting zone of the lungs. The simulations show that scond, LCI and sigmar behave quite similarly to each other, all being sensitive to increases in the severity of constriction, while exhibiting little sensitivity to the depth at which constriction occurs. In contrast, the local MRI index sigmalocal shows strong sensitivity to depth of constriction, but lowered sensitivity to constriction severity. We finish with an analysis of the sensitivity of MRI indices to grid sizes, showing that results should be interpreted with reference to the image resolution. Overall we conclude that the application of both local and global VH measures may help to classify different types of bronchoconstriction. PMID- 27677405 TI - Exercice-induced bronchoconstriction among athletes: Assessment of bronchial provocation tests. AB - Diagnosis of exercise-induced bronchoconstriction (EIB) requires the use of bronchial provocation tests (BPTs). We assessed exercise-induced respiratory symptoms (EIRS), EIB and asthma in athletes and evaluated the validity of BPTs in the diagnosis of EIB. Rhinitis and atopy were also assessed. Athletes with (n=55) and without previous asthma diagnosis (n=145) were tested by skin prick tests, lung function and eNO measurements. EIRS were recorded and EIB was assessed by methacholine (Mch), eucapnic voluntary hyperpnoea (EVH), mannitol and exercise test. EIRS were highly reported and history of asthma was common among athletes. A high prevalence of atopy (48.7%) and allergic rhinitis (30.5%) was found. Athletes with asthma had a higher response rate to Mch and to EVH, as compared with athletes without a previous asthma diagnosis (P=0.012 and P=0.017 respectively). Report of EIRS, rhinitis and atopy were not associated with a positive BPT response. Screening athletes for EIB using BPTs is suggested, irrespective of reported EIRS or a previous asthma diagnosis. PMID- 27677406 TI - Divergence of cuticular hydrocarbons in two sympatric grasshopper species and the evolution of fatty acid synthases and elongases across insects. AB - Cuticular hydrocarbons (CHCs) play a major role in the evolution of reproductive isolation between insect species. The CHC profiles of two closely related sympatric grasshopper species, Chorthippus biguttulus and C. mollis, differ mainly in the position of the first methyl group in major methyl-branched CHCs. The position of methyl branches is determined either by a fatty acid synthase (FAS) or by elongases. Both protein families showed an expansion in insects. Interestingly, the FAS family showed several lineage-specific expansions, especially in insect orders with highly diverse methyl-branched CHC profiles. We found five putative FASs and 12 putative elongases in the reference transcriptomes for both species. A dN/dS test showed no evidence for positive selection acting on FASs and elongases in these grasshoppers. However, one candidate FAS showed species-specific transcriptional differences and may contribute to the shift of the methyl-branch position between the species. In addition, transcript levels of four elongases were expressed differentially between the sexes. Our study indicates that complex methyl-branched CHC profiles are linked to an expansion of FASs genes, but that species differences can also mediated at the transcriptional level. PMID- 27677407 TI - Complete genome sequence of Fictibacillus phosphorivorans G25-29, a strain toxic to nematodes. AB - Root-knot nematodes (RKNs) which can infect almost all crops lead to huge economic losses in agriculture around the world. Unavailability of effective and environmentally friendly control of RKNs provides an opportunity to nematicidal bacteria. Fictibacillus phosphorivorans G25-29 is a gram-positive and spore forming bacterium with nematicidal capability against root-knot nematodes and free-living nematode Caenorhabditis elegans. Here, we report the complete genome of F. phosphorivorans G25-29, containing a circular chromosome and encoding nine potential nematicidal factors which may contribute to its nematicidal activity. PMID- 27677408 TI - Bird diversity and abundance in organic and conventional apple orchards in northern Japan. AB - Many studies have investigated the benefits of agri-environmental schemes, such as organic farming, on biodiversity conservation in annual systems, but their effectiveness in perennial systems is less well understood, particularly in bird communities in temperate regions of Asia. This study examined the effects of organic farming practices on species richness and abundance of breeding birds in apple orchards in northern Japan. Bird counts were conducted in six pairs of organic and conventional orchards during the breeding season in April and May 2015. The total species richness of birds, estimated by sample- and coverage based rarefaction and extrapolation curves, was greater in organic orchards than in conventional orchards. Among the three dietary guilds (insectivore, granivore, and omnivore), only insectivorous species were more abundant in organic orchards than in conventional ones. This study offers the first quantitative evidence that organic farming can be beneficial for enhancing the diversity of birds, particularly of insectivores, in fruit orchards in Japan. PMID- 27677410 TI - Roll-to-roll slot-die coating of 400 mm wide, flexible, transparent Ag nanowire films for flexible touch screen panels. AB - We report fabrication of large area Ag nanowire (NW) film coated using a continuous roll-to-roll (RTR) slot die coater as a viable alternative to conventional ITO electrodes for cost-effective and large-area flexible touch screen panels (TSPs). By controlling the flow rate of shear-thinning Ag NW ink in the slot die, we fabricated Ag NW percolating network films with different sheet resistances (30-70 Ohm/square), optical transmittance values (89-90%), and haze (0.5-1%) percentages. Outer/inner bending, twisting, and rolling tests as well as dynamic fatigue tests demonstrated that the mechanical flexibility of the slot die coated Ag NW films was superior to that of conventional ITO films. Using diamond-shape patterned Ag NW layer electrodes (50 Ohm/square, 90% optical transmittance), we fabricated 12-inch flexible film-film type and rigid glass film-film type TSPs. Successful operation of flexible TSPs with Ag NW electrodes indicates that slot-die-coated large-area Ag NW films are promising low cost, high performance, and flexible transparent electrodes for cost-effective large area flexible TSPs and can be substituted for ITO films, which have high sheet resistance and are brittle. PMID- 27677409 TI - ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism. AB - A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure. PMID- 27677412 TI - Vitiligo on black skin: epidemiological and clinical aspects in dermatology, Cotonou (Benin). AB - BACKGROUND: Vitiligo is unsightly on darkly pigmented skin and leads important stigmatization because of the mix-up with leprosy. PATIENTS AND METHODS: We analyzed retrospectively the epidemiological and clinical patterns of vitiligo on darkly pigmented skin between 1988 and 2008 in the Department of Dermatology in Cotonou (Benin). The diagnosis was made based on the clinical characteristics of vitiligo. RESULTS: Two hundred and forty-six patients were seen, representing 0.9% of new consultations. The gender ratio was 1 : 1, and the mean age of patients was 25.9 years. The mean duration of the lesions was 30.9 months. Among the 246 patients, an associated pathology was found in 26% of cases. These included atopy (23.2%), diabetes (1.6%), thyroid disease (0.8%), and alopecia (0.4%). A family history of vitiligo was present in 1.2% of cases. The sites of the lesions were in descending order of frequency: head (60.6%), lower limbs (40.2%), upper limbs (33.3%), trunk (22.4%), genitals (13.0%), and neck (8.9%). On the head, the most common sites affected were the lips (65.1%), cheek (20.8%), and ears (16.8%). According to the different clinical forms, vitiligo was achromic (76%), speckled (12.6%), and trichromic (11.4%). Vitiligo vulgaris was the commonest form of the disease (52.4%), followed by localized vitiligo (36.2%), segmental vitiligo (9.8%), and vitiligo universalis (1.6%). Triggering factors were identified in 4.5% of patients. CONCLUSION: Our survey shows that the patterns of vitiligo are similar to that reported from other African countries with a few distinguishing particularities. PMID- 27677413 TI - Interfacial Reactivity Benchmarking of the Sodium Ion Conductors Na3PS4 and Sodium beta-Alumina for Protected Sodium Metal Anodes and Sodium All-Solid-State Batteries. AB - The interfacial stability of solid electrolytes at the electrodes is crucial for an application of all-solid-state batteries and protected electrodes. For instance, undesired reactions between sodium metal electrodes and the solid electrolyte form charge transfer hindering interphases. Due to the resulting large interfacial resistance, the charge transfer kinetics are altered and the overvoltage increases, making the interfacial stability of electrolytes the limiting factor in these systems. Driven by the promising ionic conductivities of Na3PS4, here we explore the stability and viability of Na3PS4 as a solid electrolyte against metallic Na and compare it to that of Na-beta"-Al2O3 (sodium beta-alumina). As expected, Na-beta"-Al2O3 is stable against sodium, whereas Na3PS4 decomposes with an increasing overall resistance, making Na-beta"-Al2O3 the electrolyte of choice for protected sodium anodes and all-solid-state batteries. PMID- 27677411 TI - Efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access: A subgroup analysis from the bivalirudin in acute myocardial infarction versus heparin and GPI plus heparin trial. AB - OBJECTIVES: To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access. BACKGROUND: Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain. METHODS: In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30-day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding. RESULTS: 30-day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30-day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P < 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P > 0.05). CONCLUSIONS: The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. (c) 2016 Wiley Periodicals, Inc. PMID- 27677414 TI - Advantages of expanded universal carrier screening: what is at stake? AB - Expanded universal carrier screening (EUCS) entails a twofold expansion of long standing (preconception) carrier screening programmes: it not only allows the simultaneous screening of a large list of diseases ('expanded'), but also refers to a pan-ethnic screening offer ('universal'). Advocates mention three main moral advantages of EUCS as compared with traditional (targeted and/or ancestry-based) forms of carrier screening: EUCS will (1) maximise opportunities for autonomous reproductive choice by informing prospective parents about a much wider array of reproductive risks; (2) provide equity of access to carrier testing services; (3) reduce the risk of stigmatisation. This empirical ethics study aims to widen this account and provide a balanced picture of the potential pros and cons of EUCS. Semi-structured interviews were conducted with 17 health (policy) professionals and representatives of patient organisations about their views on carrier screening including a possible EUCS scenario. Stakeholders acknowledged the potential benefits of EUCS, but also expressed five main moral concerns: (1) Does EUCS respond to an urgent problem or population need? (2) Is it possible to offer couples both understandable and sufficient information about EUCS? (3) How will societal views on 'reproductive responsibility' change as a result of EUCS? (4) Will EUCS lead to a lower level of care for high-risk populations? (5) Will EUCS reinforce disability-based stigmatisation? While having the potential to overcome some moral limits inherent in traditional carrier screening, EUCS comes with moral challenges of its own. More research is needed to (further) anticipate the ethical and practical consequences of EUCS. PMID- 27677415 TI - Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and nonobstructive cardiomyopathy. AB - Oxidative phosphorylation dysfunction has been found in many different disorders. This biochemical pathway depends on mitochondrial protein synthesis. Thus, mutations in components of the mitochondrial translation system can be responsible for some of these pathologies. We identified a new homozygous missense mutation in the mitochondrial translation elongation factor Ts gene in a patient suffering from slowly progressive childhood ataxia and hypertrophic cardiomyopathy. Using cell, biochemical and molecular-genetic protocols, we confirm it as the etiologic factor of this phenotype. Moreover, as an important functional confirmation, we rescued the normal molecular phenotype by expression of the wild-type TSFM cDNA in patient's fibroblasts. Different TSFM mutations can produce the same or very different clinical phenotypes, going from abortions to moderately severe presentations. On the other hand, the same TSFM mutation can also produce same or different phenotypes within the same range of presentations, therefore suggesting the involvement of unknown factors. PMID- 27677416 TI - Registered access: a 'Triple-A' approach. AB - We propose a standard model for a novel data access tier - registered access - to facilitate access to data that cannot be published in open access archives owing to ethical and legal risk. Based on an analysis of applicable research ethics and other legal and administrative frameworks, we discuss the general characteristics of this Registered Access Model, which would comprise a three-stage approval process: Authentication, Attestation and Authorization. We are piloting registered access with the Demonstration Projects of the Global Alliance for Genomics and Health for which it may provide a suitable mechanism for access to certain data types and to different types of data users. PMID- 27677417 TI - Differential expression of parental alleles of BRCA1 in human preimplantation embryos. AB - Gene expression from both parental genomes is required for completion of embryogenesis. Differential methylation of each parental genome has been observed in mouse and human preimplantation embryos. It is possible that these differences in methylation affect the level of gene transcripts from each parental genome in early developing embryos. The aim of this study was to investigate if there is a parent-specific pattern of BRCA1 expression in human embryos and to examine if this affects embryo development when the embryo carries a BRCA1 or BRCA2 pathogenic mutation. Differential parental expression of ACTB, SNRPN, H19 and BRCA1 was semi-quantitatively analysed by minisequencing in 95 human preimplantation embryos obtained from 15 couples undergoing preimplantation genetic diagnosis. BRCA1 was shown to be differentially expressed favouring the paternal transcript in early developing embryos. Methylation-specific PCR showed a variable methylation profile of BRCA1 promoter region at different stages of embryonic development. Embryos carrying paternally inherited BRCA1 or 2 pathogenic variants were shown to develop more slowly compared with the embryos with maternally inherited BRCA1 or 2 pathogenic mutations. This study suggests that differential demethylation of the parental genomes can influence the early development of preimplantation embryos. Expression of maternal and paternal genes is required for the completion of embryogenesis. PMID- 27677418 TI - Trade-offs and efficiencies in optimal budget-constrained multispecies corridor networks. AB - Conservation biologists recognize that a system of isolated protected areas will be necessary but insufficient to meet biodiversity objectives. Current approaches to connecting core conservation areas through corridors consider optimal corridor placement based on a single optimization goal: commonly, maximizing the movement for a target species across a network of protected areas. We show that designing corridors for single species based on purely ecological criteria leads to extremely expensive linkages that are suboptimal for multispecies connectivity objectives. Similarly, acquiring the least-expensive linkages leads to ecologically poor solutions. We developed algorithms for optimizing corridors for multispecies use given a specific budget. We applied our approach in western Montana to demonstrate how the solutions may be used to evaluate trade-offs in connectivity for 2 species with different habitat requirements, different core areas, and different conservation values under different budgets. We evaluated corridors that were optimal for each species individually and for both species jointly. Incorporating a budget constraint and jointly optimizing for both species resulted in corridors that were close to the individual species movement potential optima but with substantial cost savings. Our approach produced corridors that were within 14% and 11% of the best possible corridor connectivity for grizzly bears (Ursus arctos) and wolverines (Gulo gulo), respectively, and saved 75% of the cost. Similarly, joint optimization under a combined budget resulted in improved connectivity for both species relative to splitting the budget in 2 to optimize for each species individually. Our results demonstrate economies of scale and complementarities conservation planners can achieve by optimizing corridor designs for financial costs and for multiple species connectivity jointly. We believe that our approach will facilitate corridor conservation by reducing acquisition costs and by allowing derived corridors to more closely reflect conservation priorities. PMID- 27677419 TI - Redox Behavior of the S-Adenosylmethionine (SAM)-Binding Fe-S Cluster in Methylthiotransferase RimO, toward Understanding Dual SAM Activity. AB - RimO, a radical-S-adenosylmethionine (SAM) enzyme, catalyzes the specific C3 methylthiolation of the D89 residue in the ribosomal S12 protein. Two intact iron sulfur clusters and two SAM cofactors both are required for catalysis. By using electron paramagnetic resonance, Mossbauer spectroscopies, and site-directed mutagenesis, we show how two SAM molecules sequentially bind to the unique iron site of the radical-SAM cluster for two distinct chemical reactions in RimO. Our data establish that the two SAM molecules bind the radical-SAM cluster to the unique iron site, and spectroscopic evidence obtained under strongly reducing conditions supports a mechanism in which the first molecule of SAM causes the reoxidation of the reduced radical-SAM cluster, impeding reductive cleavage of SAM to occur and allowing SAM to methylate a HS- ligand bound to the additional cluster. Furthermore, by using density functional theory-based methods, we provide a description of the reaction mechanism that predicts the attack of the carbon radical substrate on the methylthio group attached to the additional [4Fe 4S] cluster. PMID- 27677420 TI - Proteopedia entry: G-protein coupled receptors. PMID- 27677421 TI - Potentials of the elevated circulating miR-185 level as a biomarker for early diagnosis of HBV-related liver fibrosis. AB - Early diagnosis of liver fibrosis is critical for early intervention and prognosis of various chronic liver diseases. Conventional repeated histological assessment is impractical due to the associated invasiveness. In the current study, we evaluated circulating miR-185 as a potential biomarker to predict initiation and progression of liver fibrosis. We found that miR-185 was significantly up-regulated in blood specimens from patients with HBV-liver fibrosis and rats with liver fibrosis, the miR-185 levels were correlated with liver fibrosis progression, but not with the different viral loads in HBV infected patients. miR-185 was observed in collagen deposition regions during advanced liver fibrosis. We found that differences in miR-185 levels facilitated the discrimination between early-staged or advanced-staged liver fibrosis and the healthy controls with high specificity, sensitivity, and likelihood ratio using receiver-operator characteristic analysis. miR-185 targeted SREBF1, and increased expression of COL1A1 and a-SMA genes that are hallmarks of liver fibrosis. Our data supported that circulating miR-185 levels could be used as potential biomarkers for the early diagnosis of liver fibrosis. PMID- 27677422 TI - Microwave-Assisted Syntheses of Benzimidazole-Containing Selenadiazole Derivatives That Induce Cell-Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway. AB - The use of selenium-containing heterocyclic compounds as potent cancer chemopreventive and chemotherapeutic agents has been well documented by a large number of clinical studies. In this study we developed a new approach to synthesize four benzimidazole-containing selenadiazole derivatives (BSeDs). The method uses a combination of peptide coupling reagents and microwave irradiation. This strategy features milder reaction conditions, higher yields, and shorter reaction times. The synthetic BSeDs were identified as potent antiproliferative agents against the human MCF-7 and MDA-MB-231 breast cancer cell lines. Compounds 1 b (5-(6-methyl-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), 1 c (5 (6-chloro-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), and 1 d (5-(6 bromo-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole) were found to show greater cytotoxicity against the triple-negative breast cancer cell line MDA-MB 231 than MCF-7, and to exhibit dose-dependent inhibition of cell migration, in which a significant decrease in the zone of cell monolayer wound closure was observed relative to untreated controls. Our results demonstrate that BSeDs can cause cell-cycle arrest and apoptosis in MDA-MB-231 cells by inducing DNA damage, inhibiting protein kinase B (AKT), and activating mitogen-activated protein kinase (MAPK) family members through the overproduction of reactive oxygen species (ROS). Taken together, the results of this study provide a facile microwave-assisted strategy for the synthesis of selenium-containing organic compounds that exhibit a high level of anticancer efficacy. PMID- 27677423 TI - It's not what you do it's the way that it's measured: quality assessment of minor ailment management in community pharmacies. AB - BACKGROUND: Effective management of minor ailments in community pharmacies could reduce the burden on alternative high-cost services (general practices, Emergency Departments). Evidence is needed regarding the appropriateness of management of these conditions in community pharmacies. OBJECTIVE: To explore the appropriateness of minor ailment management in community pharmacies. SETTING: Prospective, observational study of simulated patient (SP) visits to community pharmacies in Grampian (Scotland) and East Anglia (England). METHOD: Eighteen pharmacies (nine per centre) were recruited within a 25-mile radius of Aberdeen or Norwich. Consultations for four minor ailments were evaluated: back pain; vomiting/diarrhoea; sore throat; and eye discomfort. Each pharmacy received one SP visit per ailment (four visits/pharmacy; 72 visits total). Visits were audio recorded and SPs completed a data collection form immediately after each visit. PRIMARY OUTCOME MEASURE: Each SP consultation was assessed for appropriateness against product licence, practice guidelines and study-specific consensus standards developed by a multi-disciplinary consensus panel. RESULTS: Evaluable data were available for 68/72 (94.4%) visits. Most (96%) visits resulted in the sale of a product; advice alone was the outcome of three visits. All product sales complied with the product licence, 52 (76%) visits complied with practice guidelines and seven visits achieved a 'basic' standard according to the consensus standard. CONCLUSION: Appropriateness of care varied according to the standard used. Pharmacy-specific quality standards are needed which are realistic and relevant to the pharmacy context and which reflect legal and clinical guidelines to promote the safe and effective management of minor ailments in this setting. PMID- 27677424 TI - Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors. AB - BACKGROUND: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. METHODS: We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher's exact test, multivariate logistic regression and Cox proportional hazards models. RESULTS: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0-113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13-4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97-12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients. CONCLUSIONS: Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS. TRIAL REGISTRATION: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005. PMID- 27677425 TI - Vectorial competence of Amblyomma tonelliae to transmit Rickettsia rickettsii. AB - The aim of this work was to test the vectorial competence of Amblyomma tonelliae (Ixodida: Ixodidae) to transmit Rickettsia rickettsii (Rickettsiales: Rickettsiaceae), the agent of Rocky Mountain spotted fever (RMSF). All parasitic stages of A. tonelliae were exposed to R. rickettsii by allowing each stage to feed on hosts inoculated with this pathogen. Thereafter, ticks were fed on uninfected hosts. All stages of A. tonelliae were able to acquire the R. rickettsii infection and maintain it by transstadial and transovarial transmission. When infected ticks fed on uninfected hosts, the hosts developed rickettsiosis disease. This study demonstrates the vectorial competence of A. tonelliae to transmit R. rickettsii. These results have epidemiological relevance because A. tonelliae is one of the tick species most likely to infest humans in Argentina, including in areas in which RMSF has been reported. PMID- 27677426 TI - Duplex detection of the Mycobacterium tuberculosis complex and medically important non-tuberculosis mycobacteria by real-time PCR based on the rnpB gene. AB - A duplex real-time PCR based on the rnpB gene was developed for Mycobacterium spp. The assay was specific for the Mycobacterium tuberculosis complex (MTB) and also detected all 19 tested species of non-tuberculous mycobacteria (NTM). The assay was evaluated on 404 clinical samples: 290 respiratory samples and 114 from tissue and other non-respiratory body sites. M. tuberculosis was detected by culture in 40 samples and in 30 samples by the assay. The MTB assay showed a sensitivity similar to Roche Cobas Amplicor MTB-PCR (Roche Molecular Systems, Pleasanton, CA, USA). There were only nine samples with non-tuberculous mycobacteria detected by culture. Six of them were detected by the PCR assay. PMID- 27677428 TI - Energy Harvesters for Wearable and Stretchable Electronics: From Flexibility to Stretchability. AB - The rapid advancements of wearable electronics have caused a paradigm shift in consumer electronics, and the emerging development of stretchable electronics opens a new spectrum of applications for electronic systems. Playing a critical role as the power sources for independent electronic systems, energy harvesters with high flexibility or stretchability have been the focus of research efforts over the past decade. A large number of the flexible energy harvesters developed can only operate at very low strain level (~0.1%), and their limited flexibility impedes their application in wearable or stretchable electronics. Here, the development of highly flexible and stretchable (stretchability >15% strain) energy harvesters is reviewed with emphasis on strategies of materials synthesis, device fabrication, and integration schemes for enhanced flexibility and stretchability. Due to their particular potential applications in wearable and stretchable electronics, energy-harvesting devices based on piezoelectricity, triboelectricity, thermoelectricity, and dielectric elastomers have been largely developed and the progress is summarized. The challenges and opportunities of assembly and integration of energy harvesters into stretchable systems are also discussed. PMID- 27677427 TI - Meat quality traits as a function of cow maturity. AB - To investigate the physico-chemical and sensory properties of striploin muscles, 90 Hanwoo carcasses (QG 1+ ) were randomly selected within six maturity levels (4 to 9 according to age in months). Results demonstrated that the protein contents at maturity levels 4 and 5 were significantly higher than 9. No significant difference in fat, moisture and collagen contents were found at different maturity levels (P > 0.05). The quantity of collagen type I and ratio of type I to III were observed at higher maturity levels; collagen type III showed significantly high levels (P > 0.05) at low maturity and decreased with increase in maturity levels. Warner-Bratzler shear force (WBSF) was significantly lower in groups 4 to 6, whereas water holding capacity (WHC) was significantly higher than maturity level 8 and 9 groups (P < 0.05). There were no significant differences in cooking loss among the maturity level groups (P > 0.05). Color properties, L* values of striploin muscle from maturity level 4 were significantly different from level 9 (P < 0.05). Sensory evaluation at level 4-6 groups had significantly higher tenderness and overall likeness scores than level 9 (P < 0.05). The maturity levels were significantly correlated with age, fat, protein content, WHC, WBSF, cooking loss, CIE L* values and sensory properties like tenderness, juiciness, flavor-likeness and overall likeness. PMID- 27677430 TI - A cascade from disregard for rules of conduct at preschool age to parental power assertion at early school age to antisocial behavior in early preadolescence: Interplay with the child's skin conductance level-CORRIGENDUM. PMID- 27677429 TI - Genistein suppresses leptin-induced proliferation and migration of vascular smooth muscle cells and neointima formation. AB - Obesity is a strong risk factor for the development of cardiovascular diseases and is associated with a marked increase in circulating leptin concentration. Leptin is a peptide hormone mainly produced by adipose tissue and is regulated by energy level, hormones and various inflammatory mediators. Genistein is an isoflavone that exhibits diverse health-promoting effects. Here, we investigated whether genistein suppressed the atherogenic effect induced by leptin. The A10 cells were treated with leptin and/or genistein, and then the cell proliferation and migration were analysed. The reactive oxygen species (ROS) and proteins levels were also measured, such as p44/42MAPK, cell cycle-related protein (cyclin D1 and p21) and matrix metalloproteinase-2 (MMP-2). Immunohistochemistry and morphometric analysis were used for the neointima formation in a rat carotid artery injury model. Genistein (5 MUM) significantly inhibited both the proliferation and migration of leptin (10 ng/ml)-stimulated A10 cells. In accordance with these finding, genistein decreased the leptin-stimulated ROS production and phosphorylation of the p44/42MAPK signal transduction pathway. Meanwhile, genistein reversed the leptin-induced expression of cyclin D1, and cyclin-dependent kinase inhibitor, p21. Genistein attenuated leptin-induced A10 cell migration by inhibiting MMP-2 activity. Furthermore, the leptin (0.25 mg/kg) augmented neointima formation in a rat carotid artery injury model was attenuated in the genistein (5 mg/kg body weight)-treated group when compared with the balloon injury plus leptin group. Genistein was capable of suppressing the atherogenic effects of leptin in vitro and in vivo, and may be a promising candidate drug in the clinical setting. PMID- 27677431 TI - Hydrogen Emission and Macromolecular Radiation-Induced Defects in Polyethylene Irradiated under an Inert Atmosphere: The Role of Energy Transfers toward trans Vinylene Unsaturations. AB - This article is aimed at studying the evolution of H2 release as well as radiation-induced defects in polyethylene (PE), as a function of the irradiation dose under anoxic conditions. We analyze the influence of the energy transfers and trapping toward radiation-induced defects on the evolution of the radiation chemical yields with dose. One key objective herein is to quantify the contribution of these transfers toward trans-vinylene (TV) on H2 emission. For this purpose, pure PE was irradiated in a large dose domain and H2 emission was compared to that in predoped PEs containing chemically inserted TV groups irradiated at low doses. In parallel, evolutions of the concentrations of the TV groups and minor defects (vinyl and trans-trans-diene) as a function of dose were considered. Moreover, measuring simultaneously H2 and unsaturated groups had allowed inferring the cross-linking evolution with dose. With this methodology, we have succeeded in quantifying the efficiency of TVs and cross-links as energy traps and, using simple models, in fully describing the evolution of all of the radiation chemical yields. Besides, irradiations were performed using either low linear energy transfer irradiations (electron beams, gamma rays) or ion beams, with the objective to assess the influence of the high ionization and excitation densities induced by the latter on PE ageing and energy transfer processes. PMID- 27677434 TI - Clinical Connections. PMID- 27677435 TI - Natural childbirth ideology is endangering women and babies. AB - Natural childbirth ideology has become dominant across much of the developed world. This ideology increasingly clashes with the reality of modern obstetrics, which is dealing with a demographic that is getting older and more obese, hence more complicated, and it has become a danger to the health of women and babies. The most visible expression of these trends is the focus on caesarean section rates which have become a key performance indicator of obstetric services. This trend is resulting in increasingly obvious negative consequences for morbidity and mortality, as chronicled in the Morecambe Bay Report, published in the UK last year. At the same time, there is mounting emphasis on patient autonomy in obstetric decision-making, which mandates informed consent. A 2015 Supreme Court decision in the UK (Montgomery vs Lanarkshire) is likely to impact on obstetric management in Australia and New Zealand. The 'paternalism in a skirt' of natural childbirth ideology is already exposing obstetricians and services to an ever increasing degree of medicolegal risk. PMID- 27677432 TI - Advances in diagnostics for transplant rejection. AB - INTRODUCTION: Identification of allograft injury, including acute clinical and subclinical injury, is vital in increasing the longevity of the transplanted organ. Acute rejection, which occurs as a result of a variety of immune and non immune factors including the infiltration of immune cells and antibodies to the donor specific epitopes, poses a significant risk to the organ. Recent years have marked an increase in the discovery of new genomic, transcriptomic, and proteomic biomarkers in molecular diagnostics, which offer better potential for personalized management of the transplanted organ by providing earlier detection of rejection episodes. Areas covered: This review was compiled from key word searches of full-text publications relevant to the field. Expert commentary: Many of the recent advancements in the molecular diagnostics of allograft injury show much promise, but before they can be fully realized further validation in larger sample sets must be conducted. Additionally, for better informed therapeutic decisions, more work must be completed to differentiate between different causes of injury. Moreover, the diagnostics field is looking at methodologies that allow for multiplexing, the ability to identify multiple targets simultaneously, in order to provide more robust biomarkers and better understanding. PMID- 27677436 TI - Computed tomography for the diagnosis of varices in liver cirrhosis: a systematic review and meta-analysis of observational studies. AB - OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) for varices in liver cirrhosis. METHODS: PubMed and EMBASE databases were searched for the literature identification. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated. We performed the subgroup analyses according to the location of varices, CT technique, and study design. The study quality was assessed according to the QUADAS-2 tool. RESULTS: Seventeen papers were eligible. The study quality was modest. The AUSROC was 0.8975 and 0.9494 for predicting any size and high-risk varices, respectively. Summary sensitivity, specificity, PLR, NLR, and DOR of CT for predicting any size and high-risk varices were 0.87/0.80/3.67/0.18/22.70 and 0.87/0.88/7.52/0.12/65.55, respectively. According to the location of varices, the AUSROC was 0.9127 for predicting any size gastric varices alone; and the AUSROC was 0.8958 and 0.9461 for predicting any size and high-risk esophageal varices alone, respectively. According to the CT technique, the AUSROC of multi detector CT (MDCT) was 0.9047 and 0.9490 for predicting any size and high-risk varices, respectively; and the AUSROC of MDCT esophagograms for predicting any size and high-risk varices was 0.8735 and 0.9664, respectively. In the subgroup analysis of prospective studies, the AUSROC was 0.9122 and 0.9507 for predicting any size and high-risk varices, respectively. CONCLUSION: CT had a high accuracy for the diagnosis of varices in liver cirrhosis. PMID- 27677437 TI - Childhood bullying victimization is associated with use of mental health services over five decades: a longitudinal nationally representative cohort study. AB - BACKGROUND: Research supports robust associations between childhood bullying victimization and mental health problems in childhood/adolescence and emerging evidence shows that the impact can persist into adulthood. We examined the impact of bullying victimization on mental health service use from childhood to midlife. METHOD: We performed secondary analysis using the National Child Development Study, the 1958 British Birth Cohort Study. We conducted analyses on 9242 participants with complete data on childhood bullying victimization and service use at midlife. We used multivariable logistic regression models to examine associations between childhood bullying victimization and mental health service use at the ages of 16, 23, 33, 42 and 50 years. We estimated incidence and persistence of mental health service use over time to the age of 50 years. RESULTS: Compared with participants who were not bullied in childhood, those who were frequently bullied were more likely to use mental health services in childhood and adolescence [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.88-3.40] and also in midlife (OR 1.30, 95% CI 1.10-1.55). Disparity in service use associated with childhood bullying victimization was accounted for by both incident service use through to age 33 years by a subgroup of participants, and by persistent use up to midlife. CONCLUSIONS: Childhood bullying victimization adds to the pressure on an already stretched health care system. Policy and practice efforts providing support for victims of bullying could help contain public sector costs. Given constrained budgets and the long-term mental health impact on victims of bullying, early prevention strategies could be effective at limiting both individual distress and later costs. PMID- 27677438 TI - First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome. AB - PURPOSE: Maternal thyroid gland dysfunction may adversely affect pregnancy outcome. We aimed to examine the association between subclinical thyroid dysfunction, both hypothyroidism and hyperthyroidism, to adverse pregnancy outcome. MATERIALS AND METHODS: Retrospective cohort study of all women with an available first trimester thyroid function testing and known pregnancy outcome, categorized to subclinical hypothyroidism, or hyperthyroidism and evaluated for complication during gestation and delivery. RESULTS: Four thousand five hundred and four women were included in the final analysis - 3231 were euthyroid, 73 (1.6%) were categorized as subclinical hyperthyroidism and 1200 (26.6%) had subclinical hypothyroidism. Low thyroid-stimulating hormone (TSH) levels, i.e. subclinical hyperthyroidism, correlates with higher rates of placental abruption and extremely low birth weight, below 1500 g. Also, the risk for preterm delivery prior to 34 gestational weeks is higher among women with subclinical hypothyroidism, with greater risk among those with a higher TSH level. (OR 1.81, 95% CI 1.0-3.28 for TSH 2.5-4.0 mIU/L and OR 2.33, 95% CI 1.11-4.42 for those with TSH > 4 4.0 mIU/L). CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk for preterm delivery prior to 34 gestational weeks. Additionally, subclinical hyperthyroidism may also have a role in adverse pregnancy outcome - low birth weight and placental abruption - although this needs to be further explored. PMID- 27677439 TI - Systematic genotyping of groups of cows to improve genomic estimated breeding values of selection candidates. AB - BACKGROUND: Extending the reference set for genomic predictions in dairy cattle by adding large numbers of cows with genotypes and phenotypes has been proposed as a means to increase reliability of selection decisions for candidates. METHODS: In this study, we explored the potential of increasing the reliability of breeding values of young selection candidates by genotyping a fixed number of first-crop daughters of each sire from one or two generations in a balanced and regular system of genotyping. Using stochastic simulation, we developed a basic population scenario that mimics the situation in dual-purpose Fleckvieh cattle with respect to important key parameters. Starting with a reference set consisting of only genotyped bulls, we extended this reference set by including increasing numbers of daughter genotypes and phenotypes. We studied the effects on model-derived reliabilities, validation reliabilities and unbiasedness of predicted values for selection candidates. We also illustrate and discuss the effects of a selected sample and an unbalanced sampling of daughters. Furthermore, we quantified the role of selection with respect to the influence on validation reliabilities and contrasted these to model-derived reliabilities. RESULTS: In the most extended design, with 200 daughters per sire genotyped from two generations, single nucleotide polymorphism (SNP) effects were estimated from a reference set of 420,000 cows and 4200 bulls. For this design, the validation reliabilities for candidates reached 80 % or more, thereby exceeding the reliabilities that were achieved in traditional progeny-testing designs for a trait with moderate to high heritability. We demonstrate that even a moderate number of 25 genotyped daughters per sire will lead to considerable improvement in the reliability of predicted breeding values for selection candidates. Our results illustrate that the strategy applied to sample females for genotyping has a large impact on the benefits that can be achieved. PMID- 27677440 TI - A comprehensive review of reviews of school-based interventions to improve sexual health. AB - OBJECTIVE: To systematically review systematic reviews of school-based sexual health and relationship Education (SHRE) programmes and, thereby, identify interventions and intervention components that promote reductions in risky sexual behaviour among young people. METHODS: Electronic bibliographies were searched systematically to identify systematic reviews of school-based interventions targeting sexual-health. Results were summarised using a narrative synthesis. RESULTS: Thirty-seven systematic reviews (summarising 224 primary randomised controlled trials) met our inclusion and quality assessment criteria. In general, these reviews analysed distinct sets of primary studies, and no comprehensive review of available primary studies was identified. Interventions were categorised into five types that segment this review literature. Unfortunately, many reviews reported weak and inconsistent evidence of behaviour change. Nonetheless, integration of review findings generated a list of 32 design, content and implementation characteristics that may enhance effectiveness of school-based, sexual-health interventions. Abstinence-only interventions were found to be ineffective in promoting positive changes in sexual behaviour. By contrast, comprehensive interventions, those specifically targeting HIV prevention, and school-based clinics were found to be effective in improving knowledge and changing attitudes, behaviours and health-relevant outcomes. CONCLUSIONS: School-based interventions targeting risky sexual behaviour can be effective. Particular design, content and implementation characteristics appear to be associated with greater effectiveness. We recommend consideration of these characteristics by designers of school-based sexual-health interventions. PMID- 27677441 TI - Trends in smoking prevalence and attributable mortality in China, 1991-2011. AB - OBJECTIVE: China is the largest producer of tobacco worldwide. We assessed secular trends in prevalence of smoking, average cigarettes per day, mean age of initiation, and mortality attributable to smoking among the Chinese population between 1991 and 2011. DESIGN: Data came from the China Health and Nutrition Survey, conducted eight times between 1991 and 2011. A total of 83,447 participants aged 15years or older were included in this study. Trends in smoking were stratified by sex, age, and region (urban vs. rural). RESULTS: In 2011, 311 millions individuals were current smokers in China, with 295 million men and 16 million women, respectively. Between 1991 and 2011, the prevalence of current smoking decreased from 60.6% to 51.6% in men, and from 4.0% to 2.9% in women. However, during this period, the average number of cigarettes smoked per day per smoker increased from 15.0 to 16.5 in males, and from 8.5 to 12.4 in females. Further, age of smoking initiation decreased from 21.9 to 21.4years in men and from 31.4 to 28.4years in women. In 2011, 16.5% of all deaths in men and 1.7% in women were due to smoking. Between 1991 and 2011, the total number of deaths caused by smoking increased from 800,000 to 900,000. CONCLUSIONS: During the past 20years, a slight decrease in smoking prevalence was observed in the Chinese population. However, cigarette smoking remains a major cause of death in China, especially in men. PMID- 27677442 TI - Associations between explorative dietary patterns and serum lipid levels and their interactions with ApoA5 and ApoE haplotype in patients with recently diagnosed type 2 diabetes. AB - AIMS: In patients with type 2 diabetes (T2D), responsiveness of serum lipid concentrations to dietary patterns may vary by genotype. The aims of the present study were to identify explorative dietary patterns and to examine their independent associations with serum lipid levels and interactions with apolipoprotein (Apo)A5 and ApoE variants among patients recently diagnosed with T2D. METHODS: Within a cross-sectional analysis, participants of the German Diabetes Study (n = 348) with mean T2D duration of 6 months were investigated for fasting serum lipid levels, ApoA5 and ApoE genotypes; food consumption frequencies were assessed by a food propensity questionnaire. Dietary patterns were derived using principal component analysis (PCA) and reduced rank regression (RRR), which extracts patterns explaining variation in serum lipid concentrations. RESULTS: PCA yielded interpretable dietary patterns which were, however, not related to serum lipid levels. Relevance of the RRR patterns varied by genotype: a preferred consumption of fruit gum, fruit juice, and potato dumpling, whilst avoiding fruits and vegetables independently associated with higher triglyceride levels among ApoA5*2. Patients in the highest compared to the lowest tertile of pattern adherence had 99 % higher triglycerides. Lower consumption frequencies of butter, cream cake, French fries, or high-percentage alcoholic beverages were independently related to lower LDL-cholesterol among ApoE2 carriers, with those in the highest compared to the lowest tertile of pattern adherence having 40 % lower LDL-cholesterol (both Pinteraction < 0.05). CONCLUSIONS: Our explorative data analyses suggest that associations of dietary patterns with triglycerides and LDL-cholesterol differ by ApoA5 and ApoE haplotype in recently diagnosed T2D. Trial registration Clinicaltrials.gov: NCT01055093. Date of registration: January 22, 2010 (retrospectively registered). Date of enrolment of first participant to the trial: September 2005. PMID- 27677443 TI - Care Consistency With Documented Care Preferences: Methodologic Considerations for Implementing the "Measuring What Matters" Quality Indicator. AB - A basic tenet of palliative care is discerning patient treatment preferences and then honoring these preferences, reflected by the inclusion of "Care Consistency With Documented Care Preferences" as one of 10 "Measuring What Matters quality" indicators. Measuring What Matters indicators are intended to serve as a foundation for quality measurement in health care settings. However, there are a number of logistic and practical issues to be considered in the application of this quality indicator to clinical practice. In this brief methodologic report, we describe how care consistency with documented care preferences has been measured in research on patients near the end of life. Furthermore, we outline methodologic challenges in using this indicator in both research and practice, such as documentation, specificity and relevance, preference stability, and measuring nonevents. Recommendations to strengthen the accuracy of measurement of this important quality marker in health care settings include consistent recording of preferences in the medical record, considerations for selection of treatment preferences for tracking, establishing a protocol for review of preferences, and adoption of a consistent measurement approach. PMID- 27677444 TI - Citation bias favoring positive clinical trials of thrombolytics for acute ischemic stroke: a cross-sectional analysis. AB - BACKGROUND: Citation bias occurs when positive trials involving a medical intervention receive more citations than neutral or negative trials of similar quality. Several large clinical trials have studied the use of thrombolytic agents for the treatment of acute ischemic stroke with differing results, thereby presenting an opportunity to assess these trials for evidence of citation bias. We compared citation rates among positive, neutral, and negative trials of alteplase (tPA) and other thrombolytic agents for stroke. METHODS: We used a 2014 Cochrane Review of thrombolytic therapy for the treatment of acute stroke to identify non-pilot, English-language stroke trials published in MEDLINE-indexed journals comparing thrombolytic therapy with control. We classified trials as positive if there was a statistically significant primary outcome difference favoring the intervention, neutral if there was no difference in primary outcome, or negative for a significant primary outcome difference favoring the control group. Trials were also considered negative if safety concerns supported stopping the trial early. Using Scopus, we collected citation counts through 2015 and compared citation rates according to trial outcomes. RESULTS: Eight tPA trials met inclusion criteria: two were positive, four were neutral, and two were negative. The two positive trials received 9080 total citations, the four neutral trials received 4847 citations, and the two negative trials received 1096 citations. The mean annual per-trial citation rates were 333 citations per year for positive trials, 96 citations per year for neutral trials, and 35 citations per year for negative trials. Trials involving other thrombolytic agents were not cited as often, though as with tPA, positive trials were cited more frequently than neutral or negative trials. CONCLUSIONS: Positive trials of tPA for ischemic stroke are cited approximately three times as often as neutral trials, and nearly 10 times as often as negative trials, indicating the presence of substantial citation bias. PMID- 27677445 TI - Long-term outcome and health-related quality of life in difficult-to-wean patients with and without ventilator dependency at ICU discharge: a retrospective cohort study. AB - BACKGROUND: Long-term outcome and quality of life (QOL) in patients requiring prolonged mechanical ventilation after failure to wean in the ICU is scarcely documented. We aimed to evaluate long-term survival and QOL in patients discharged from the ICU with a tracheostomy for difficult weaning, and with or without ventilator dependency at ICU discharge. METHODS: We retrospectively investigated post-ICU trajectories and survival in patients requiring tracheostomy for difficult weaning admitted to the medical ICU of a tertiary center between 1999 and 2013, discriminating between patients who were ventilator dependent or were weaned at ICU discharge. In 2014, a QOL assessment was done in survivors with the use of the Short Form Health Survey (SF-36) and the Severe Respiratory Insufficiency questionnaire. RESULTS: A total of 114 patients was included, of whom 59 were ventilator dependent and 55 were weaned at ICU discharge. One-year survival rates were 73 % and 69 %, respectively. Overall QOL scores for physical functioning were low, and not significantly different between patients ventilated and those weaned at ICU discharge; scores for social functioning and mental health were less below norm and similar between both groups. CONCLUSIONS: Long-term survival in patients discharged from the ICU with tracheostomy and ventilator dependency after failure to wean was not significantly different from that of patients with tracheostomy and weaned at ICU discharge. Despite the physical QOL scores being low in both groups, mental QOL was acceptable. Given the intrinsic limitations of this retrospective study, prospective and preferentially multicenter studies are required to confirm these preliminary results. PMID- 27677447 TI - Adrenaline use is associated with excess organ injury and mortality in cardiogenic shock: facts and fiction. PMID- 27677448 TI - Acute coronary syndrome in dextrocardia and situs inversus patient. PMID- 27677446 TI - In-store marketing of inexpensive foods with good nutritional quality in disadvantaged neighborhoods: increased awareness, understanding, and purchasing. AB - BACKGROUND: Consumers often do not understand nutrition labels or do not perceive their usefulness. In addition, price can be a barrier to healthy food choices, especially for socio-economically disadvantaged individuals. METHOD: A 6-month intervention combined shelf labeling and marketing strategies (signage, prime placement, taste testing) to draw attention to inexpensive foods with good nutritional quality in two stores located in a disadvantaged neighborhood in Marseille (France). The inexpensive foods with good nutritional quality were identified based on their nutrient profile and their price. Their contribution to customers' spending on food was assessed in the two intervention stores and in two control stores during the intervention, as well as in the year preceding the intervention (n = 6625). Exit survey (n = 259) and in-depth survey (n = 116) were used to assess customers' awareness of and perceived usefulness of the program, knowledge of nutrition, understanding of the labeling system, as well as placement-, taste- and preparation-related attractiveness of promoted products. Matched purchasing data were used to assess the contribution of promoted products to total food spending for each customer who participated in the in-depth survey. RESULTS: The contribution of inexpensive foods with good nutritional quality to customers' total food spending increased between 2013 and 2014 for both the control stores and the intervention stores. This increase was significantly higher in the intervention stores than in the control stores for fruits and vegetables (p = 0.001) and for starches (p = 0.011). The exit survey revealed that 31 % of customers had seen the intervention materials; this percentage increased significantly at the end of the intervention (p < 0.001). The in-depth survey showed that customers who had seen the intervention materials scored significantly higher on quizzes assessing nutrition knowledge (p < 0.001) and understanding of the labeling system (p = 0.024). CONCLUSION: A social marketing intervention aimed at increasing the visibility and attractiveness of inexpensive foods with good nutritional quality may improve food purchasing behaviors in disadvantaged neighborhoods. PMID- 27677449 TI - [Percentage of psychoemotional problems in Spanish children and adolescents. Differences between 2006 and 2012]. AB - BACKGROUND AND OBJECTIVE: To examine the percentage of psychoemotional problems in Spanish children and adolescents and the difference between 2006 and 2012. MATERIAL AND METHOD: Data from 9,761 participants were taken from the Spanish National Health Survey of 2006 and 2012. The Goodman Strengths and Difficulties Questionnaire was used to assess mental health. The percentage of participants with abnormal scores in the different scales was calculated. Chi-square test and multivariate logistic regression models adjusted for age, sex, social level and adult mental health status were used. RESULTS: In 2012, the percentage of Spanish youths with emotional, conduct, hyperactivity, peer and prosocial problems and abnormal total problem score was 8.5, 6.7, 10.2, 7.7, 0.7 and 4%, respectively. In 2006, these percentages were 11.5, 10.2, 14.7, 10.1, 0.9 and 6.7%. A significant reduction was found for the percentage of children and adolescents with problematic behavior between 2006 and 2012. CONCLUSIONS: Based on the total problem score, about 4% of Spanish youths suffer from psychoemotional problems. This percentage has decreased between 2006 and 2012. PMID- 27677450 TI - Tuberous sclerosis: Fatty degeneration of rhabdomyoma. PMID- 27677451 TI - Raman gas self-organizing into deep nano-trap lattice. AB - Trapping or cooling molecules has rallied a long-standing effort for its impact in exploring new frontiers in physics and in finding new phase of matter for quantum technologies. Here we demonstrate a system for light-trapping molecules and stimulated Raman scattering based on optically self-nanostructured molecular hydrogen in hollow-core photonic crystal fibre. A lattice is formed by a periodic and ultra-deep potential caused by a spatially modulated Raman saturation, where Raman-active molecules are strongly localized in a one-dimensional array of nanometre-wide sections. Only these trapped molecules participate in stimulated Raman scattering, generating high-power forward and backward Stokes continuous wave laser radiation in the Lamb-Dicke regime with sub-Doppler emission spectrum. The spectrum exhibits a central line with a sub-recoil linewidth as low as ~14 kHz, more than five orders of magnitude narrower than conventional-Raman pressure broadened linewidth, and sidebands comprising Mollow triplet, motional sidebands and four-wave mixing. PMID- 27677452 TI - Comparative expression and regulation of duplicated fibroblast growth factor 1 genes in grass carp (Ctenopharyngodon idella). AB - Fibroblast growth factor 1 (Fgf1) is known as a mitogenic factor involved in the regulation of cell growth, proliferation, and differentiation in vertebrates. Here, we report the isolation and characterization of two fgf1 genes in grass carp (Ctenopharyngodon idella). Grass carp fgf1a and fgf1b cDNAs are highly divergent, sharing a relatively low amino acid sequence identity of 50%, probably due to fish-specific gene duplication. fgf1a and fgf1b mRNAs were detected in the zygote and expressed throughout embryogenesis. Both fgf1a and fgf1b mRNAs were primarily detectable in the notochord at 12 hpf. At 24 hpf, fgf1a mRNA was mainly expressed in the gut and somites, while fgf1b transcript persisted in the notochord and was detected in the tailbud. At 36 hpf, both fgf1a and fgf1b transcripts were detected in the brain, somites, and tailbud. In addition, the fgf1a mRNA was detected at the base of the yolk sac, whereas the fgf1b mRNA was expressed in the pectoral fin. In adult fish, duplicated fgf1a and fgf1b mRNAs were distributed in most tissues. After 2-6days of starvation, both fgf1a and fgf1b mRNAs were upregulated in the muscle and liver. In the brain, fgf1a mRNA was upregulated, while fgf1b mRNA was significantly downregulated at 6days. Furthermore, both fgf1a and fgf1b mRNA levels were significantly decreased in the brain and muscle after administration of 10 or 50MUg of the human growth hormone (hGH),while their mRNA levels were no significant difference in the liver. These results suggest that duplicated fgf1s may play important but divergent roles in the grass carp development. PMID- 27677453 TI - PARP, transcription and chromatin modeling. AB - Compaction mode of chromatin and chromatin highly organised structures regulate gene expression. Posttranslational modifications, histone variants and chromatin remodelers modulate the compaction, structure and therefore function of specific regions of chromatin. The generation of poly(ADP-ribose) (PAR) is emerging as one of the key signalling events on sites undergoing chromatin structure modulation. PAR is generated locally in response to stresses. These include genotoxic stress but also differentiation signals, metabolic and hormonal cues. A pictures emerges in which transient PAR formation is essential to orchestrate chromatin remodelling and transcription factors allowing the cell to adapt to alteration in its environment. This review summarizes the diverse factors of ADP-ribosylation in the adaptive regulation of chromatin structure and transcription. PMID- 27677456 TI - The use of extra-analytical phase quality indicators by clinical laboratories: the results of an international survey. PMID- 27677454 TI - Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria. AB - Oral cancer, primarily oral squamous cell carcinoma (OSCC), continues to be a major global health problem with high incidence and low survival rates. While the major risk factors for this malignancy, mostly lifestyle related, have been identified, around 15% of oral cancer cases remain unexplained. In light of evidence implicating bacteria in the aetiology of some cancer types, several epidemiological studies have been conducted in the last decade, employing methodologies ranging from traditional culture techniques to 16S rRNA metagenomics, to assess the possible role of bacteria in OSCC. While these studies have demonstrated differences in microbial composition between cancerous and healthy tissues, they have failed to agree on specific bacteria or patterns of oral microbial dysbiosis to implicate in OSCC. On the contrary, some oral taxa, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, show strong oral carcinogenic potential in vitro and in animal studies. Bacteria are thought to contribute to oral carcinogenesis via inhibition of apoptosis, activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation, and production of carcinogens. This narrative review provides a critical analysis of and an update on the association between bacteria and oral carcinogenesis and the possible mechanisms underlying it. PMID- 27677457 TI - Coherent and dynamic beam splitting based on light storage in cold atoms. AB - We demonstrate a coherent and dynamic beam splitter based on light storage in cold atoms. An input weak laser pulse is first stored in a cold atom ensemble via electromagnetically-induced transparency (EIT). A set of counter-propagating control fields, applied at a later time, retrieves the stored pulse into two output spatial modes. The high visibility interference between the two output pulses clearly demonstrates that the beam splitting process is coherent. Furthermore, by manipulating the control lasers, it is possible to dynamically control the storage time, the power splitting ratio, the relative phase, and the optical frequencies of the output pulses. With further improvements, the active beam splitter demonstrated in this work might have applications in photonic photonic quantum information and in all-optical information processing. PMID- 27677455 TI - Exercise protects against methamphetamine-induced aberrant neurogenesis. AB - While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus. PMID- 27677458 TI - Characterization and Potential Applications of a Selenium Nanoparticle Producing and Nitrate Reducing Bacterium Bacillus oryziterrae sp. nov. AB - A novel nitrate- and selenite reducing bacterium strain ZYKT was isolated from a rice paddy soil in Dehong, Yunnan, China. Strain ZYKT is a facultative anaerobe and grows in up to 150, 000 ppm O2. The comparative genomics analysis of strain ZYKT implies that it shares more orthologues with B. subtilis subsp. subtilis NCIB 3610T (ANIm values, 85.4-86.7%) than with B. azotoformans NBRC 15712T (ANIm values, 84.4-84.7%), although B. azotoformans NBRC 15712T (96.3% 16S rRNA gene sequence similarity) is the closest Bacillus species according to 16S rRNA gene comparison. The major cellular fatty acids of strain ZYKT were iso-C14:0 (17.8%), iso-C15:0 (17.8%), and C16:0 (32.0%). The polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unidentified aminophospholipid. Based on physiological, biochemical and genotypic properties, the strain was considered to represent a novel species of the genus Bacillus, for which the name Bacillus oryziterrae sp. nov. is proposed. The type strain is ZYKT (=DSM 26460T =CGMCC 1.5179T). Strain ZYKT can reduce nitrate to nitrite and ammonium and possesses metabolic genes for nitrate reduction including nar, nap and nrf. Biogenic selenium nanoparticles of strain ZYKT show a narrow size distribution and agree with the gaussian distribution. These selenium nanoparticles show significant dose-dependent inhibition of the lung cancer cell line H157, which suggests potential for application in cancer therapy. PMID- 27677459 TI - An Effective and Inducible System of TAL Effector-Mediated Transcriptional Repression in Arabidopsis. PMID- 27677460 TI - Rice Ferredoxin-Dependent Glutamate Synthase Regulates Nitrogen-Carbon Metabolomes and Is Genetically Differentiated between japonica and indica Subspecies. AB - Plants assimilate inorganic nitrogen absorbed from soil into organic forms as Gln and Glu through the glutamine synthetase/glutamine:2-oxoglutarate amidotransferase (GS/GOGAT) cycle. Whereas GS catalyzes the formation of Gln from Glu and ammonia, GOGAT catalyzes the transfer of an amide group from Gln to 2 oxoglutarate to produce two molecules of Glu. However, the regulatory role of the GS/GOGAT cycle in the carbon-nitrogen balance is not well understood. Here, we report the functional characterization of rice ABNORMAL CYTOKININ RESPONSE 1 (ABC1) gene that encodes a ferredoxin-dependent (Fd)-GOGAT. The weak mutant allele abc1-1 mutant shows a typical nitrogen-deficient syndrome, whereas the T DNA insertional mutant abc1-2 is seedling lethal. Metabolomics analysis revealed the accumulation of an excessive amount of amino acids with high N/C ratio (Gln and Asn) and several intermediates in the tricarboxylic acid cycle in abc1-1, suggesting that ABC1 plays a critical role in nitrogen assimilation and carbon nitrogen balance. Five non-synonymous single-nucleotide polymorphisms were identified in the ABC1 coding region and characterized as three distinct haplotypes, which have been highly and specifically differentiated between japonica and indica subspecies. Collectively, these results suggest that ABC1/OsFd-GOGAT is essential for plant growth and development by modulating nitrogen assimilation and the carbon-nitrogen balance. PMID- 27677461 TI - Single-cell SNP analyses and interpretations based on RNA-Seq data for colon cancer research. AB - Single-cell sequencing is useful for illustrating the cellular heterogeneities inherent in many intricate biological systems, particularly in human cancer. However, owing to the difficulties in acquiring, amplifying and analyzing single cell genetic material, obstacles remain for single-cell diversity assessments such as single nucleotide polymorphism (SNP) analyses, rendering biological interpretations of single-cell omics data elusive. We used RNA-Seq data from single-cell and bulk colon cancer samples to analyze the SNP profiles for both structural and functional comparisons. Colon cancer-related pathways with single cell level SNP enrichment, including the TGF-beta and p53 signaling pathways, were also investigated based on both their SNP enrichment patterns and gene expression. We also detected a certain number of fusion transcripts, which may promote tumorigenesis, at the single-cell level. Based on these results, single cell analyses not only recapitulated the SNP analysis results from the bulk samples but also detected cell-to-cell and cell-to-bulk variations, thereby aiding in early diagnosis and in identifying the precise mechanisms underlying cancers at the single-cell level. PMID- 27677462 TI - Development of a novel high-entropy alloy with eminent efficiency of degrading azo dye solutions. AB - In addition to its scientific importance, the degradation of azo dyes is of practical significance from the perspective of environmental protection. Although encouraging progress has been made on developing degradation approaches and materials, it is still challenging to fully resolve this long-standing problem. Herein, we report that high entropy alloys, which have been emerging as a new class of metallic materials in the last decade, have excellent performance in degradation of azo dyes. In particular, the newly developed AlCoCrTiZn high entropy alloy synthesized by mechanical alloying exhibits a prominent efficiency in degradation of the azo dye (Direct Blue 6: DB6), as high as that of the best metallic glass reported so far. The newly developed AlCoCrTiZn HEA powder has low activation energy barrier, i.e., 30 kJ/mol, for the degrading reaction and thus make the occurrence of reaction easier as compared with other materials such as the glassy Fe-based powders. The excellent capability of our high-entropy alloys in degrading azo dye is attributed to their unique atomic structure with severe lattice distortion, chemical composition effect, residual stress and high specific surface area. Our findings have important implications in developing novel high-entropy alloys for functional applications as catalyst materials. PMID- 27677464 TI - Synergistic reactivation of latent HIV-1 provirus by PKA activator dibutyryl-cAMP in combination with an HDAC inhibitor. AB - HIV-1 reservoirs remain a major barrier to HIV-1 eradication. Although combination antiretroviral therapy (cART) can successfully reduce viral replication, it cannot reactivate HIV-1 provirus in this reservoir. Therefore, HIV-1 provirus reactivation strategies by cell activation or epigenetic modification are proposed for the eradication of HIV-1 reservoirs. Although treatment with the protein kinase A (PKA) activator cyclic AMP (cAMP) or epigenetic modifying agents such as histone deacetylase inhibitors (HDACi) alone can induce HIV-1 reactivation in latently infected cells, the synergism of these agents has not been fully evaluated. In the present study, we observed that treatment with 500MUM of dibutyryl-cAMP, 1MUM of vorinostat, or 1MUM of trichostatin A alone effectively reactivated HIV-1 in both ACH2 and NCHA1 cells latently infected with HIV-1 without cytotoxicity. In addition, treatment with the PKA inhibitor KT5720 reduced the increased HIV-1 p24 level in the supernatant of these cells. After dibutyryl-cAMP treatment, we found an increased level of the PKA substrate phosphorylated cyclic AMP response element-binding protein. When we treated cells with a combination of dibutyryl-cAMP and vorinostat or trichostatin A, the levels of HIV-1 p24 in the supernatant and levels of intracellular HIV-1 p24 were dramatically increased in both ACH2 and NCHA1 cells compared with those treated with a single agent. These results suggest that combined treatment with a PKA activator and an HDACi is effective for reactivating HIV-1 in latently infected cells, and may be an important approach to eradicate HIV-1 reservoirs. PMID- 27677463 TI - Efficient delivery of C/EBP beta gene into human mesenchymal stem cells via polyethylenimine-coated gold nanoparticles enhances adipogenic differentiation. AB - The controlled differentiation of stem cells via the delivery of specific genes encoding appropriate differentiation factors may provide useful models for regenerative medicine and aid in developing therapies for human patients. However, the majority of non-viral vectors are not efficient enough to manipulate difficult-to-transfect adult human stem cells in vitro. Herein, we report the first use of 25 kDa branched polyethylenimine-entrapped gold nanoparticles (AuPEINPs) and covalently bound polyethylenimine-gold nanoparticles (AuMUAPEINPs) as carriers for efficient gene delivery into human mesenchymal stem cells (hMSCs). We determined a functional application of these nanoparticles by transfecting hMSCs with the C/EBP beta gene, fused to EGFP, to induce adipogenic differentiation. Transfection efficacy with AuPEINPs and AuMUAPEINPs was 52.3% and 40.7%, respectively, which was 2.48 and 1.93 times higher than that by using Lipofectamine 2000. Luciferase assay results also demonstrated improved gene transfection efficiency of AuPEINPs/AuMUAPEINPs over Lipofectamine 2000 and polyethylenimine. Overexpression of exogenous C/EBP beta significantly enhanced adipogenesis in hMSCs as indicated by both of Oil Red O staining and mRNA expression analyses. Nanoparticle/DNA complexes exhibited favorable cytocompatibility in hMSCs. Taken together, AuPEINPs and AuMUAPEINPs potentially represent safe and highly efficient vehicles for gene delivery to control hMSC differentiation and for therapeutic gene delivery applications. PMID- 27677465 TI - No PERV transmission during a clinical trial of pig islet cell transplantation. AB - Xenotransplantation of pig islet cells is a promising alternative for the treatment of diabetes with insulin and may help to prevent numerous late complications such as blindness and amputation. First encouraging results using porcine islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated islet cells from the well-characterised Auckland Island pigs were used. The animals were not genetically modified. The islet cells were transplanted in eight human recipients using a modified clinical protocol. Sera taken at different time points after transplantation (up to 55 weeks) were screened for the presence of antibodies against PERV proteins by Western blot analysis using viral antigens from highly purified virus particles. Positive sera obtained by immunization with recombinant PERV proteins were used as control sera. In none of the patients antibodies against PERV were detected, indicating the absence of infection. In parallel at different time points (up to 113 weeks) white blood cells (WBC) have been tested for PERV DNA, and WBC and plasma for PERV RNA by real-time RT-PCR. All tests were negative. In addition, using primers detecting pig mitochondrial cytochrome oxidase (COX) gene, patients were screened for microchimerism. In summary, the data are further evidence for the safety of pig islet cell transplantation. PMID- 27677467 TI - Arterial Stiffness in Treated Hypertensive Patients With White-Coat Hypertension. AB - Arterial stiffness, assessed through pulse wave velocity (PWV), independently predicts cardiovascular outcomes. In untreated persons, white-coat hypertension (WCH) has been related to arterial stiffness, but data in treated patients with WCH are scarce. The authors aimed to determine a possible association between WCH and arterial stiffness in this population. Adult treated hypertensive patients underwent home blood pressure monitoring and PWV assessment. Variables associated with PWV in univariable analyses were entered into a multivariable linear regression model. The study included 121 patients, 33.9% men, median age 67.9 (interquartile range 18.4) years, 5.8% with diabetes, and 3.3% with a history of cardiovascular or cerebrovascular disease. In multivariable analysis, WCH in treated hypertensive patients remained a determinant of PWV: beta=1.1 (95% confidence interval, 0.1-2.1 [P=.037]; adjusted R2 0.49). In conclusion, WCH is independently associated with arterial stiffness in treated hypertensive patients. Whether this high-risk association is offset by antihypertensive treatment should be further investigated. PMID- 27677468 TI - Corrigendum: Hydrogel microphones for stealthy underwater listening. PMID- 27677466 TI - Gain-of-function defects of astrocytic Kir4.1 channels in children with autism spectrum disorders and epilepsy. AB - Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10. We detected germline heterozygous KCNJ10 variants in 19/175 affected children. Epileptic spasms with dysregulated sensory processing represented the main disease phenotype. When investigated on astrocyte-like cells, the p.R18Q mutation exerted a gain-of-function effect by enhancing Kir4.1 membrane expression and current density. Similarly, the p.R348H variant led to gain of channel function through hindrance of pH-dependent current inhibition. The frequent polymorphism p.R271C seemed, instead, to have no obvious functional effects. Our results confirm that variants in KCNJ10 deserve attention in autism-epilepsy, and provide insight into the molecular mechanisms of autism and seizures. Similar to neurons, astrocyte dysfunction may result in abnormal synaptic transmission and electrical discharge, and should be regarded as a possible pharmacological target in autism epilepsy. PMID- 27677469 TI - Pulmonary metastasectomy in elderly colorectal cancer patients: a retrospective single center study. AB - Colorectal cancer (CRC) is one of the most common malignancies worldwide and the lung is one of the most frequent sites for CRC metastasis. The geriatric population is increasing, but clinical decision making is often influenced by the effect of aging. For this reason, the elderly population does not often receive potentially curative cancer treatments as offered to younger ones. From January 2000 to March 2016, 21 elderly patients (older than 75 years) underwent pulmonary resections for colorectal cancer pulmonary metastases. A postoperative morbidity rate of 23.8 % and a 30-day mortality rate of 4.8 % were reported. A cumulative overall survival of 34.19 +/- 23.51 months (95 % CI 23.71-50.28) and a disease free interval of 24.62 +/- 23.79 months (95 % CI 6.44-39.56) were observed. By considering only R0 surgically resected patients, the 1-, 3- and 5-year OS were 94.1, 59.5 and 21.2 % with a mean overall survival and disease-free interval of 51.10 +/- 7.82 and 42.75 +/- 9.35, respectively. Concerning risk factors, an important correlation between the number of pulmonary metastases, surgical radicality and overall survival was reported (p = 0.030 and p = 0.005, respectively). In summary, according to our series, pulmonary metastasectomy in selected elderly CRC oligometastatic patients seems to be safe and effective. PMID- 27677470 TI - T-drain reduces the incidence of biliary leakage after liver resection. AB - Biliary leakage is a serious complication after liver resection and represents the major cause of post-operative morbidity. In spite of already identified risk factors, little is known about the role of intra-biliary pressure following liver surgery in the development of biliary leakage. Biliary decompression may have a positive impact and reduce the incidence of biliary leakage at the parenchymal resection site. 397 patients undergoing liver resection without bilioenteric anastomosis were included in the retrospective analysis of the risk factors for the development of biliary leakage focusing on the intra-operative reduction of the biliary pressure by T-tube and liver histology. Among 397 analyzed patients after parenchymal resection, biliary leakage occurred in 39 cases (9.8 %). The extent of parenchymal resection was not associated with the total occurrence of biliary leak (p = 0.626). Lower incidence of biliary leakage from the resection surface was significantly associated with the use of T-tube (4.9 vs. 13.2 %; p = 0.006). In the subgroup analysis, insertion of a T-tube was not associated with a reduction of biliary leakage after anatomical hemihepatectomies (p = 0.103) and extraanatomical liver resection (p = 0.676). However, a high statistical significance could be detected in patients with extended hemihepatectomies (58.3 vs. 3.8 %; p < 0.001). Once biliary leak occurred without T-tube, median hospitalization duration significantly increased compared to patients with biliary decompression and without biliary leak (p < 0.001). The results of our retrospective data analysis suggest a significant beneficial impact of the T-tube on the development of biliary leakage in patients undergoing extended liver surgery. PMID- 27677471 TI - Multiple metrics of diversity have different effects on temperate forest functioning over succession. AB - Biodiversity can be measured by taxonomic, phylogenetic, and functional diversity. How ecosystem functioning depends on these measures of diversity can vary from site to site and depends on successional stage. Here, we measured taxonomic, phylogenetic, and functional diversity, and examined their relationship with biomass in two successional stages of the broad-leaved Korean pine forest in northeastern China. Functional diversity was calculated from six plant traits, and aboveground biomass (AGB) and coarse woody productivity (CWP) were estimated using data from three forest censuses (10 years) in two large fully mapped forest plots (25 and 5 ha). 11 of the 12 regressions between biomass variables (AGB and CWP) and indices of diversity showed significant positive relationships, especially those with phylogenetic diversity. The mean tree diversity-biomass regressions increased from 0.11 in secondary forest to 0.31 in old-growth forest, implying a stronger biodiversity effect in more mature forest. Multi-model selection results showed that models including species richness, phylogenetic diversity, and single functional traits explained more variation in forest biomass than other candidate models. The models with a single functional trait, i.e., leaf area in secondary forest and wood density in mature forest, provided better explanations for forest biomass than models that combined all six functional traits. This finding may reflect different strategies in growth and resource acquisition in secondary and old-growth forests. PMID- 27677472 TI - Nonparametric estimation of the multivariate survivor function: the multivariate Kaplan-Meier estimator. AB - The Dabrowska (Ann Stat 16:1475-1489, 1988) product integral representation of the multivariate survivor function is extended, leading to a nonparametric survivor function estimator for an arbitrary number of failure time variates that has a simple recursive formula for its calculation. Empirical process methods are used to sketch proofs for this estimator's strong consistency and weak convergence properties. Summary measures of pairwise and higher-order dependencies are also defined and nonparametrically estimated. Simulation evaluation is given for the special case of three failure time variates. PMID- 27677473 TI - Effectiveness of antimicrobial photodynamic therapy (AmPDT) on Staphylococcus aureus using phenothiazine compound with red laser. AB - The aim of this study was to evaluate, in vitro, the bactericidal effect of antimicrobial photodynamic therapy (AmPDT) using phenothiazinium dyes (Toluidine Blue O and methylene blue, 1:1) using different concentrations (100, 50, 25, 12.5, and 6.25 MUg/mL) associated to red laser with different energy densities (2.4, 4.8, 7.2, 9.6, and 12 J/cm2) on a strain of Staphylococcus aureus (ATCC 23529). On this study, tests were performed in triplicate and the samples were distributed into 36 test groups: Control and bacterial suspensions were irradiated with the different energy densities, respectively, in the absence of photosensitizer, bacterial suspensions were irradiated with the laser in the different concentrations of the photosensitizer, and finally bacterial suspensions only in the presence of phenothiazinium dye. The pre-irradiation time was 5 min. Therefore, we analyzed the potential of the AmPDT by counting colony forming units. The logarithm of CFU/mL (log10 CFU/mL) was calculated and the data was analyzed statistically (ANOVA, Tukey's test, p < 0.05). The results showed that the association 50 and 100 MUg/mL with 12 J/cm2 showed the highest percentage of inhibition (100 %). Based upon the present results, it may be concluded that the AmPDT was able to enhance the antimicrobial effect of phenothiazines and both concentration of the compound and energy density are important factors for greater effectiveness of therapy. PMID- 27677474 TI - Comparison of thulium laser enucleation and plasmakinetic resection of the prostate in a randomized prospective trial with 5-year follow-up. AB - The aim of this study was to compare the clinical outcomes between thulium laser enucleation of the prostate (ThuLEP) and plasmakinetic bipolar resection of the prostate (PKRP) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial with 5 years of follow-up. One hundred fifty-eight consecutive patients with BPH were randomized to receive operation of either ThuLEP (n = 79) or PKRP (n = 79). All cases were evaluated preoperatively, and a part of them were evaluated at 3-5 years postoperatively by the International Prostate Symptom Score (IPSS), quality of life score (QoLS), maximum flow rate (Q max), and postvoid residual (PVR) urine volume. Eighty patients completed the 5-year follow up. Each study arm showed no significant difference in preoperative parameters. Compared with PKRP, ThuLEP required longer operation time (65.4 vs 47.4 min, p = 0.022) but resulted in less hemoglobin decrease (1.5 vs 3.0 g/L, p = 0.045), catheterization time (2.1 vs 3.5 days, p = 0.031), irrigated volume (12.4 vs 27.2 L, p = 0.022), and hospital stay (2.5 vs 4.6 days, p = 0.026). During the 60 month follow-up, both procedures demonstrated no significant difference in terms of Q max, IPSS, PVR urine volume, and QoLS. ThuLEP was statistically superior to PKRP in blood loss, catheterization time, irrigated volume, and hospital stay but inferior to PKRP in operation time. However, both procedures showed no significant difference in terms of Q max, IPSS, PVR urine volume, and QoLS through the 60-month follow-up. PMID- 27677475 TI - Effects of low-level laser therapy and epidermal growth factor on the activities of gingival fibroblasts obtained from young or elderly individuals. AB - This study evaluated the effects of low-level laser therapy (LLLT) and epidermal growth factor (EGF) on fibroblasts obtained from young and elderly individuals. Gingival fibroblasts from young (Y) and elderly (E) individuals were seeded in wells of 24-well plates with Dulbecco's modified Eagle's medium (DMEM) containing 10 % of fetal bovine serum (FBS). After 24 h, the cells were irradiated (LASERTable-InGaAsP-780 +/- 3 nm, 25 mW, 3 J/cm2) or exposed to EGF (100 MUM). After 72 h, cells were evaluated for viability, migration, collagen and vascular endothelial growth factor (VEGF) synthesis, and gene expression of growth factors. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests (alpha = 5 %). Y and E fibroblasts irradiated with laser or exposed to EGF showed increased viability and collagen synthesis. Enhanced cell migration was observed for Y fibroblasts after both treatments, whereas only the LLLT stimulated migration of E cells. VEGF synthesis was higher for Y and E cells exposed to EGF, while this synthesis was reduced when E fibroblasts were irradiated. Increased gene expression of VEGF was observed only for Y and E fibroblasts treated with LLLT. Regardless of a patient's age, the LLLT and EGF applications can biostimulate gingival fibroblast functions involved in tissue repair. PMID- 27677477 TI - Erratum to: Ablation of carious dental tissue using an ultrashort pulsed laser (USPL) system. PMID- 27677476 TI - Effect of photodynamic therapy with malachite green on non-surgical periodontal treatment in HIV patients: a pilot split-mouth study. PMID- 27677479 TI - Effect of pH on the isolation of urinary exosome. AB - PURPOSE: Urinary exosome is an ideal noninvasive, low-cost source of kidney diseases biomarkers. However, many factors effect the isolation of urine-derived exosome. The effect of pH on the yield of exosome isolation under different pH was explored. METHODS: The pH was adjusted for 4, 5, 6, 7 and 8 with hydrochloric acid and sodium hydroxide solution. All samples were incubated for 30 min before differential ultracentrifugation. Exosome-associated protein markers TSG101, ALIX and total concentration of RNA were evaluated by Western-blotting and micro amount ultraviolet spectrophotometer, respectively. RESULTS: A major loss of urinary exosome was received at pH 8 compared with alkali medium or control group. There was no difference whether or not added EDTA-Na2. CONCLUSIONS: Acidic environment was likely to conducive to the isolation of exosome and maintain its stability and integrity that suggest pH medium needs to be carefully considered and also provide a methodology for future separation exosome. PMID- 27677478 TI - The evaluation of prepared microgroove pattern by femtosecond laser on alumina zirconia nano-composite for endosseous dental implant application. AB - Ceramic dental materials, especially alumina (20 %vol)-yttrium stabilized tetragonal zirconia poly crystal (A-Y-TZP20), have been considered as alternatives to metals for endosseous dental implant application. For increasing the bone-to-implant contact as well as the speed of bone formation, a new surface modification can be effective. The aim of this study was to design microgroove patterns by femtosecond laser on A-Y-TZP20 nano-composite disks for endosseous dental implant application. The phase composition and the morphology of the A-Y TZP20 nano-composite samples were characterized using X-ray diffraction and Scanning electron microscopy equipped with energy dispersive X-ray spectroscopy techniques. Statistical analysis was submitted to Kolmogorov-Smirnov test and Student's t test for independent variables, with a 5 % significance level. EDAX analysis revealed a significant decrease in the relative content of contaminants like carbon (p < 0.05) in laser surface-treated group as compared to non surface treated group. X-ray diffraction did not show any change in the crystalline structure induced by laser processing. It was concluded that the femtosecond laser is a clean and safe method for surface modification of A-Y-TZP20. PMID- 27677480 TI - NF-kappaB expression and its association with nutritional status in hemodialysis patients. AB - PURPOSE: This study aimed to evaluate the association among the expressions of pro- and anti-inflammatory nuclear factors (nuclear factor-kappaB, NF-kappaB and nuclear erythroid 2-related factor 2, Nrf2) and nutritional status in HD patients. METHODS: This cross-sectional study included eighty-three HD patients. The peripheral blood mononuclear cells were isolated and processed for the evaluation of NF-kappaB and Nrf2 RNAm expression by quantitative real-time polymerase chain reaction. Muscle mass was estimated by creatinine index (CI) and percentage of body fat (%BF) by anthropometry. Seven-point subjective global assessment was also used to evaluate the nutritional status. RESULTS: The NF kappaB expression was negatively correlated with CI (r = -0.54, p = 0.0001), serum albumin (r = -0.32, p = 0.02) and %BF (r = -0.61, p = 0.001). Multiple linear regression analysis revealed that NF-kappaB expression was independently associated with CI (beta: -0.8, p = 0.013) and %BF (beta: -0.42, p = 0.04). There was no correlation among Nrf2 and anthropometric and biochemical variables. CONCLUSION: The classical NF-kappaB activation seems to be associated with poor nutritional status in HD patients; however, the exact underlying mechanisms deserve further studies. PMID- 27677481 TI - The Role of Panobinostat Plus Bortezomib and Dexamethasone in Treating Relapsed or Relapsed and Refractory Multiple Myeloma: A European Perspective. AB - : Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received >=2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population. The authorization and recommendation were based on results from the pivotal phase 3 PANORAMA 1 (NCT01023308) clinical trial, which demonstrated an improvement in median progression-free survival of 7.8 months for the three-drug combination compared with placebo plus bortezomib and dexamethasone in this patient population. This review will discuss the current treatment landscape for relapsed/refractory MM, the mechanism of action of panobinostat, clinical data supporting the European authorization, concerns about safety and strategies for mitigating toxicity, and how panobinostat fits into the current MM landscape in Europe. FUNDING: Editorial support, funded by Novartis Pharmaceuticals. PMID- 27677482 TI - Characterization of pax3a and pax3b genes in artificially induced polyploid and gynogenetic olive flounder (Paralichthys olivaceus) during embryogenesis. AB - Although chromosome set manipulation techniques including polyploidy induction and gynogentic induction in flatfish are becoming increasingly mature, there exists a poor understanding of their effects on embryonic development. PAX3 plays crucial roles during embryonic myogenesis and neurogenesis. In olive flounder (Paralichthys olivaceus), there are two duplicated pax3 genes (pax3a, pax3b), and both of them are expressed in the brain and muscle regions with some subtle regional differences. We utilized pax3a and pax3b as indicators to preliminarily investigate whether chromosome set manipulation affects embryonic neurogenesis and myogenesis using whole-mount in situ hybridization. In the polyploid induction groups, 94 % of embryos in the triploid induction group had normal pax3a/3b expression patterns; however, 45 % of embryos in the tetraploid induction group showed abnormal pax3a/3b expression patterns from the tailbud formation stage to the hatching stage. Therefore, the artificial induction of triploidy and tetraploidy had a small or a moderate effect on flounder embryonic myogenesis and neurogenesis, respectively. In the gynogenetic induction groups, 87 % of embryos in the meiogynogenetic diploid induction group showed normal pax3a/3b expression patterns. However, almost 100 % of embryos in the gynogenetic haploid induction group and 63 % of embryos in the mitogynogenetic diploid induction group showed abnormal pax3a/3b expression patterns. Therefore, the induction of gynogenetic haploidy and mitogynogenetic diploidy had large effects on flounder embryonic myogenesis and neurogenesis. In conclusion, the differential expression of pax3a and pax3b may provide new insights for consideration of fish chromosome set manipulation. PMID- 27677483 TI - Effects of dietary yeast inclusion and acute stress on post-prandial whole blood profiles of dorsal aorta-cannulated rainbow trout. AB - Yeast is a potential alternative to fish meal in diets for farmed fish, yet replacing more than 50 % of fish meal results in reduced fish growth. In a 4-week experiment, 15 rainbow trout (Oncorhynchus mykiss) were cannulated and fed three diets each week: 30 % fish meal as a control (FM); 60 % replacement of fish meal protein, on a digestible basis, with Saccharomyces cerevisiae (SC); and 60 % replacement with Wickerhamomyces anomalus and S. cerevisiae mix (WA). Blood was collected at 0, 3, 6, 12 and 24 h after feeding. In the final week, fish were exposed to a 1-min netting stressor to evaluate possible diet-stress interactions. Significant increases in pH, TCO2, HCO3 and base excess were found after fish were fed the SC and WA diets compared with FM, which elevated blood alkaline tides. Yeast ingredients had lower buffering capacity and ash content than fish meal, which explained the increase in alkaline tides. In addition, fish fed the WA diet had significantly reduced erythrocyte area and fish fed SC and WA diets had increased mean corpuscular haemoglobin levels, indicating haemolytic anaemia. Higher levels of nucleic acid in yeast-based diets and potentially higher production of reactive oxygen species were suspected of damaging haemoglobin, which require replacement by smaller immature erythrocytes. Acute stress caused the expected rise in cortisol and glucose levels, but no interaction with diet was found. These results show that replacing 60 % of fish meal protein with yeasts can induce haemolytic anaemia in rainbow trout, which may limit yeast inclusion in diets for farmed fish. PMID- 27677484 TI - Transient cessation of antiplatelet medication before percutaneous stone surgery: does it have any safety concern on bleeding related problems? AB - To evaluate the short term effects of transient AP medication cessation on the safety of percutaneous nephrolithotomy (PCNL) and evaluate them with normal cases in a comparative manner. 71 cases undergoing PCNL for renal pelvic stones were divided into two groups: Group 1 (n: 35) Cases under AP medication (100 mg/day acetyl salicylic acid) in whom the medication was stopped for 7 days before PCNL procedure. Group 2 (n: 36) Cases without any AP medication prior to PCNL. Coagulation test parameters were normal in all cases prior to stone removal. Treatment related parameters with an emphasis on post-operative course were evaluated between two groups. While prolonged macroscopic hematuria (mean 3.5 days) was present in a 25.7 % of the cases in Group 1; it was 5.7 % in Group 2 (mean 2 days). Mean duration of nephrostomy tube was longer in Group 1 (3.49 vs 2.64 days respectively). Additionally, hospitalization period was longer in cases under antiplatelet therapy when compared with the others. No statistically significant difference was noted between two groups regarding post-operative Hb drop rates, transfusion, fever, embolization rates. Lastly, of all the risk factors evaluated; use of AP medication was found to increase the risk of macroscopic hematuria 5.8-fold on logistic regression analysis. Our findings demonstrated that despite the cessation of the antiplatelet agents with an appropriate regimen; these cases should be followed for the risk of prolonged hematuria and tube drainage after PCNL in a very close manner. PMID- 27677486 TI - Malabsorption "Non Olet". PMID- 27677485 TI - Cross-cultural adaptation and validation of the SNOT-22 into Italian. AB - The aim of this study is to evaluate the reliability and validity of the Italian SNOT-22 (I-SNOT-22). The study consisted of five phases: item generation, reliability analysis, normative data generation, validity analysis and responsiveness analysis. The item generation phase followed the five-step, cross cultural, adaptation process of translation and back-translation. A group of 222 patients with chronic rhinosinusitis (CRS) were enrolled for the internal consistency analysis. Sixty patients completed the I-SNOT-22 twice, 2 weeks apart, for test-retest reliability analysis. A group of 119 asymptomatic subjects completed the I-SNOT-22 for normative data generation. I-SNOT-22 scores obtained by CRS patients and asymptomatic subjects were compared for validity analysis. I SNOT-22 scores were correlated with Lund-Mackay and visual analogue scale (VAS) scores in 50 CRS patients for criterion validity analysis. Finally, I-SNOT-22 scores obtained in a group of 59 CRS patients before and after surgical treatment for CRS were compared for responsiveness analysis. All the enrolled subjects managed to complete the I-SNOT-22 without needing any assistance. Internal consistency was satisfactory (alpha = 0.86). Test-retest reliability was also satisfactory (ICC = 0.85). A significant difference in the I-SNOT-22 scores between the CRS patients and the asymptomatic subjects was found (p < 0.008). Positive significant correlations were found between I-SNOT-22 and VAS scores, while no significant correlations were found between I-SNOT-22 scores and Lund Mackay scores. I-SNOT-22 scores obtained in the pre-treatment condition were significantly higher than those obtained after surgery. I-SNOT-22 is reliable, valid, responsive to changes in QOL, and recommended for clinical practice and outcome research. PMID- 27677488 TI - Stapleless Laparoscopic Sleeve Gastrectomy: a Relatively New Approach in Bariatric Surgery. PMID- 27677487 TI - A Comparative Study Examining the Impact of a Protein-Enriched Vs Normal Protein Postoperative Diet on Body Composition and Resting Metabolic Rate in Obese Patients after Sleeve Gastrectomy. AB - BACKGROUND: We recently showed that an 8-week preoperative protein-enriched diet (PED) is associated with significant reductions in body weight and fat mass (FM) without significant loss of fat-free mass (FFM) in morbidly obese patients scheduled for laparoscopic sleeve gastrectomy (LSG). OBJECTIVES: The objective of this study is to evaluate the impact of PED vs a normal protein diet (NPD) on total weight loss (TWL), FM, FFM, and resting metabolic rate (RMR) in patients after LSG. METHODS: Before LSG and at 3, 6, and 12 months after, we prospectively measured and compared total body weight (TBW), FM, FFM, and RMR in 60 male patients who received either a NPD (n = 30) with protein intake 1.0 g/kg of ideal body weight, or a PED (n = 30) with protein intake 2.0 g/kg of ideal body weight. Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of NPD and PED on renal function was also evaluated. RESULTS: Despite non-significant variation in total body weight (TBW), FM decreased more significantly (p < 0.01) with the PED compared to the NPD. In addition, the PED group showed a significantly (p < 0.01) lower decrease in FFM and RMR when compared with the NPD group. Both groups showed high compliance in following the prescribed diets, without negative impact on renal function. CONCLUSION: PED is more effective than NPD in determining FM loss and is associated with a lower decrease in FFM and RMR, without interfering with renal function in male patients after LSG. PMID- 27677489 TI - Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy. AB - Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status >= grade 2 (p = 0.005), elevated lactate dehydrogenase ratio >1 (p < 0.001), advanced Ann Arbor stage (p = 0.002), and bulky disease (p = 0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR] = 1.967, 95 % confidence interval [CI] = 1.399-2.765, p < 0.001; OS, HR = 2.445, 95 % CI = 1.689-3.640, p < 0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy. PMID- 27677490 TI - Diagnostic utility of invasive EEG for epilepsy surgery: Indications, modalities, and techniques. AB - Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost-benefit. These recommendations aim to curtail outlying indications that risk the over- or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource-poor regions around the world. PMID- 27677491 TI - microRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3' untranslated region: function in replication and influence of RNA secondary structure. AB - We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3'UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3'UTR target site inhibits translation directed by the HCV 5'UTR. Thus, the miR-122 target sites in the 3'-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle. PMID- 27677494 TI - Polarized Thin Layer Deposited Electrochemically on Aluminum-Doped Zinc Oxide as a Cathode Interlayer for Highly Efficient Organic Electronics. AB - Herein, we demonstrated a polarized thin film (PBzP2C4) electrochemically deposited from phosphonate and a carbazole-difunctionalized conjugated molecule as an aluminum-doped zinc oxide (AZO) modifier for high-performance inverted organic solar cells (OSCs)/polymer light-emitting diodes (PLEDs). The PBzP2C4 film showed a controllable thickness and fully covered the surface of AZO, resulting in a smooth and uniform electrode. PBzP2C4 modification reduced the WF of AZO and highly improved the electron extraction/injection in inverted OSCs/PLEDs. As a result, a maximum power conversion efficiency of 10.35% was achieved for inverted OSCs with PTB7-Th:PC71BM as the active layer, and a maximum luminous efficiency of 21.4 cd A-1 was obtained for inverted PLEDs based on P PPV. PMID- 27677495 TI - Expression of lycopene biosynthesis genes fused in line with Shine-Dalgarno sequences improves the stress-tolerance of Lactococcus lactis. AB - OBJECTIVES: Lycopene biosynthetic genes from Deinococcus radiodurans were co expressed in Lactococcus lactis to produce lycopene and improve its tolerance to stress. RESULTS: Lycopene-related genes from D. radiodurans, DR1395 (crtE), DR0862 (crtB), and DR0861 (crtI), were fused in line with S hine-Dalgarno (SD) sequences and co-expressed in L. lactis. The recombinant strain produced 0.36 mg lycopene g-1 dry cell wt after 48 h fermentation. The survival rate to UV irradiation of the recombinant strain was higher than that of the non-transformed strain. CONCLUSION: The L. lactis with co-expressed genes responsible for lycopene biosynthesis from D. radiodurans produced lycopene and exhibited increased resistance to UV stress, suggesting that the recombinant strain has important application potential in food industry. PMID- 27677496 TI - A Framework for Evaluating Value of New Clinical Recommendations. PMID- 27677493 TI - Heritability of targeted gene modifications induced by plant-optimized CRISPR systems. AB - The Streptococcus-derived CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) system has emerged as a very powerful tool for targeted gene modifications in many living organisms including plants. Since the first application of this system for plant gene modification in 2013, this RNA-guided DNA endonuclease system has been extensively engineered to meet the requirements of functional genomics and crop trait improvement in a number of plant species. Given its short history, the emphasis of many studies has been the optimization of the technology to improve its reliability and efficiency to generate heritable gene modifications in plants. Here we review and analyze the features of customized CRISPR/Cas9 systems developed for plant genetic studies and crop breeding. We focus on two essential aspects: the heritability of gene modifications induced by CRISPR/Cas9 and the factors affecting its efficiency, and we provide strategies for future design of systems with improved activity and heritability in plants. PMID- 27677492 TI - Regulation of mRNA decay in plant responses to salt and osmotic stress. AB - Plant acclimation to environmental stresses requires fast signaling to initiate changes in developmental and metabolic responses. Regulation of gene expression by transcription factors and protein kinases acting upstream are important elements of responses to salt and drought. Gene expression can be also controlled at the post-transcriptional level. Recent analyses on mutants in mRNA metabolism factors suggest their contribution to stress signaling. Here we highlight the components of mRNA decay pathways that contribute to responses to osmotic and salt stress. We hypothesize that phosphorylation state of proteins involved in mRNA decapping affect their substrate specificity. PMID- 27677497 TI - [Workshop for surgical skills in Cologne by GeSRU]. PMID- 27677498 TI - Genetic origin, admixture and population history of aurochs (Bos primigenius) and primitive European cattle. AB - The domestication of taurine cattle initiated ~10 000 years ago in the Near East from a wild aurochs (Bos primigenius) population followed by their dispersal through migration of agriculturalists to Europe. Although gene flow from wild aurochs still present at the time of this early dispersion is still debated, some of the extant primitive cattle populations are believed to possess the aurochs like primitive features. In this study, we use genome-wide single nucleotide polymorphisms to assess relationship, admixture patterns and demographic history of an ancient aurochs sample and European cattle populations, several of which have primitive features and are suitable for extensive management. The principal component analysis, the model-based clustering and a distance-based network analysis support previous works suggesting different histories for north-western and southern European cattle. Population admixture analysis indicates a zebu gene flow in the Balkan and Italian Podolic cattle populations. Our analysis supports the previous report of gene flow between British and Irish primitive cattle populations and local aurochs. In addition, we show evidence of aurochs gene flow in the Iberian cattle populations indicating wide geographical distribution of the aurochs. Runs of homozygosity (ROH) reveal that demographic processes like genetic isolation and breed formation have contributed to genomic variations of European cattle populations. The ROH also indicate recent inbreeding in southern European cattle populations. We conclude that in addition to factors such as ancient human migrations, isolation by distance and cross-breeding, gene flow between domestic and wild-cattle populations also has shaped genomic composition of European cattle populations. PMID- 27677499 TI - Anti-interleukin 5 Therapy for Eosinophilic Asthma: a Meta-analysis of Randomized Clinical Trials. AB - Recently, more and more clinical trials have been performed to evaluate the effects of anti-interleukin (IL)-5 antibodies in eosinophilic asthma. However, a confirm conclusion has not been well established. We therefore sought to conduct a meta-analysis to assess the overall efficacy and safety of anti-interleukin 5 treatments in eosinophilic asthma. RCTs of anti-interleukin 5 treatments in eosinophilic asthma published up to June 2016 in PubMed, Embase, Cochrane library databases, and CBM, which reported pulmonary functions, quality-of-life scores, asthmatic exacerbations, and adverse events were included. Fixed-effect models were used to calculate mean difference, relative risks (RR), and 95 % CIs. Twelve studies involving 3340 patients were identified. Pooled analysis revealed significant improvements in FEV1 (nine trials, 1935 subjects; MD = 0.12; 95 % CI, 0.08-0.16), and Asthma Quality-of-Life Questionnaire scores (five trials, 1334 subjects; MD = 0.23; 95 % CI, 0.13-0.34). Anti-interleukin 5 treatment was also associated with significantly decreased exacerbation risk than placebo (six trials, 875 subjects; RR = 0.52; 95 % CI, 0.46 to 0.59) and a lower incidence of adverse events (eight trials, 1754 subjects; RR = 0.93; 95 % CI, 0.89 to 0.97). Anti-interleukin 5 treatment is well tolerated and could significantly improve FEV1, quality of life, and reduced exacerbations risk in patients with eosinophilic asthma. Further trials are necessary to assess the baseline blood eosinophil count to identify the optimal patients of eosinophilic asthma that could benefit from anti-interleukin 5 therapy. PMID- 27677502 TI - Protein coingestion with alcohol following strenuous exercise attenuates alcohol induced intramyocellular apoptosis and inhibition of autophagy. AB - Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation is unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurrent exercise with either postexercise ingestion of alcohol and carbohydrate (12 +/- 2 standard drinks; ALC-CHO), energy-matched alcohol and protein (ALC-PRO), or protein (PRO) only. Muscle biopsies were taken at rest and 2 and 8 h postexercise. Select autophagy-related gene (Atg) proteins decreased compared with rest with ALC-CHO (P < 0.05) but not ALC-PRO. There were parallel increases (P < 0.05) in p62 and PINK1 commensurate with a reduction in BNIP3 content, indicating a diminished capacity for mitochondria-specific autophagy (mitophagy) when alcohol and carbohydrate were coingested. DNA fragmentation increased in both alcohol conditions (P < 0.05); however, nuclear AIF accumulation preceded this apoptotic response with ALC-CHO only (P < 0.05). In contrast, increases in the nuclear content of p53, TFEB, and PGC-1alpha in ALC PRO were accompanied by markers of mitochondrial biogenesis at the transcriptional (Tfam, SCO2, and NRF-1) and translational (COX-IV, ATPAF1, and VDAC1) level (P < 0.05). We conclude that alcohol ingestion following exercise triggers apoptosis, whereas the anabolic properties of protein coingestion may stimulate mitochondrial biogenesis to protect cellular homeostasis. PMID- 27677501 TI - Diagnostic Potential of Extracellular MicroRNA in Respiratory Diseases. AB - Lack of markers of subclinical disease state and clinical phenotype other than pulmonary function test has made the diagnosis and interventions of environmental respiratory diseases a major challenge. MicroRNAs (miRNAs), small non-coding single stranded RNAs, have emerged as potential disease-modifier in various environmental respiratory diseases. They can also be found in various body fluids and are remarkably stable. Because of their high stability, disease-specific expression, and the ease to detect and quantify them have raised the potential of miRNAs in body fluids to be useful clinical diagnostic biomarkers for lung disease phenotyping. In the present review, we provide a comprehensive overview of progress made in identifying miRNAs in various body fluids including blood, serum, plasma, bronchoalveolar lavage (BAL) fluid, and sputum as biomarkers for a wide range of human respiratory diseases such as acute lung injury/acute respiratory distress syndrome (ALI/ARDS), idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and asthma. Finally, we discuss several challenges remain to be concerned and suggest few disease-specific and non-specific miRNAs to become part of future clinical practice. PMID- 27677503 TI - Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial. AB - OBJECTIVE: To test the optimal antithrombotic regimen in patients with acute coronary syndrome. DESIGN: Randomised controlled trial. SETTING: Patients with acute coronary syndrome with and without ST segment elevation in 78 centres in Italy, the Netherlands, Spain, and Sweden. PARTICIPANTS: 7213 patients with acute coronary syndrome and planned percutaneous coronary intervention: 4010 with ST segment elevation and 3203 without ST segment elevation. The primary study results in the overall population have been reported previously. INTERVENTIONS: Patients were randomly assigned, in an open label fashion, to one of two regimens: bivalirudin with glycoprotein IIb/IIIa inhibitors restricted to procedural complications or heparin with or without glycoprotein IIb/IIIa inhibitors. MAIN OUTCOME MEASURES: Primary endpoints were the occurrence of major adverse cardiovascular events, defined as death, myocardial infarction or stroke; and net adverse clinical events, defined as major bleeding or major adverse cardiovascular events, both assessed at 30 days. Analyses were performed by the principle of intention to treat. RESULTS: Use of a glycoprotein IIb/IIIa inhibitor in patients assigned to heparin was planned at baseline in 30.7% of patients with ST segment elevation, in 10.9% without ST segment elevation, and in no patients assigned to bivalirudin. In patients with ST segment elevation, major adverse cardiovascular events occurred in 118 (5.9%) assigned to bivalirudin and 129 (6.5%) assigned to heparin (rate ratio 0.90, 95% confidence interval 0.70 to 1.16; P=0.43), whereas net adverse clinical events occurred in 139 (7.0%) patients assigned to bivalirudin and 163 (8.2%) assigned to heparin (0.84, 0.67 to 1.05; P=0.13). In patients without ST segment elevation, major adverse cardiovascular events occurred in 253 (15.9%) assigned to bivalirudin and 262 (16.4%) assigned to heparin (0.97, 0.80 to 1.17; P=0.74), whereas net adverse clinical events occurred in 262 (16.5%) patients assigned to bivalirudin and 281 (17.6%) assigned to heparin (0.93, 0.77 to 1.12; P=0.43). CONCLUSIONS: A bivalirudin monotherapy strategy compared with heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.Trial Registration ClinicalTrials.gov NCT01433627. PMID- 27677504 TI - Statins in Primary Prevention: Uncertainties and Gaps in Randomized Trial Data. AB - Randomized controlled trials (RCTs) have provided evidence of the usefulness of statin primary prevention in lowering cardiovascular morbidity and mortality, yet uncertainties and gaps remain. The objective of this article was to perform a narrative review of RCTs of statins for primary prevention and identify uncertainties and gaps resulting from the design of individual studies. Such knowledge is important for informed physician-patient decisions. A literature search was conducted for RCTs of statins in primary prevention that included >1000 general patients and clinical outcomes as a primary endpoint. A total of 11 RCTs were identified; target population baseline characteristics, outcomes measures, statistical methods, and limitations regarding follow-up were reported. RCTs of statins in primary prevention show consistent overall beneficial effects on cardiovascular morbidity and mortality. Caveats involve the characteristics of individual study populations since target populations often differ from what is currently considered primary prevention. Only middle aged and older populations were adequately represented in these RCTs; women were under-represented. Only one study included total mortality as the primary endpoint; all other RCTs used composite major adverse cardiac events as the primary endpoint, which occasionally included a hard outcome such as death and a soft outcome such as hospitalization for angina. The use of Cox proportional hazard analysis in RCTs poses some challenges, and intention-to-treat analysis may mask adverse events. An understanding of the deficiencies of individual RCTs of statins in primary prevention is important in creating a patient-specific therapeutic clinical decision and in tailoring future research. PMID- 27677500 TI - Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes. AB - As physiological pathways of intercellular communication produced by all cells, cytokines are involved in the pathogenesis of inflammatory insulitis as well as pivotal mediators of immune homeostasis. Proinflammatory cytokines including interleukins, interferons, transforming growth factor-beta, tumor necrosis factor alpha, and nitric oxide promote destructive insulitis in type 1 diabetes through amplification of the autoimmune reaction, direct toxicity to beta-cells, and sensitization of islets to apoptosis. The concept that neutralization of cytokines may be of therapeutic benefit has been tested in few clinical studies, which fell short of inducing sustained remission or achieving disease arrest. Therapeutic failure is explained by the redundant activities of individual cytokines and their combinations, which are rather dispensable in the process of destructive insulitis because other cytolytic pathways efficiently compensate their deficiency. Proinflammatory cytokines are less redundant in regulation of the inflammatory reaction, displaying protective effects through restriction of effector cell activity, reinforcement of suppressor cell function, and participation in islet recovery from injury. Our analysis suggests that the role of cytokines in immune homeostasis overrides their contribution to beta-cell death and may be used as potent immunomodulatory agents for therapeutic purposes rather than neutralized. PMID- 27677505 TI - Optimizing the Use of Cangrelor in the Real World. AB - Thrombotic events such as myocardial infarction or stent thrombosis are the major cause of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). While current antiplatelet agents, anticoagulants, and PCI techniques have reduced the risk of thrombotic events in PCI-treated patients, a considerable hazard still remains. Cangrelor is an intravenous P2Y12 receptor antagonist that provides a rapid onset and maximal platelet inhibition, which is quickly reversible. In the large-scale CHAMPION PHOENIX trial, cangrelor was shown to reduce ischemic events significantly, including myocardial infarction and stent thrombosis, without increasing the risk of severe bleeding across the full spectrum of patients undergoing PCI, with substantial benefits in all patient subgroups examined. The pharmacologic profile of cangrelor makes it a valuable addition to the armamentarium of physicians providing care to a broad range of patients with coronary artery disease. Cangrelor is currently approved for reducing thrombotic events in patients undergoing PCI who have not been pretreated with a P2Y12 receptor inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor. Future studies are needed to determine the role of cangrelor in other clinical settings, such as upstream therapy in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and as a bridge to coronary artery bypass graft (CABG) or other non-cardiac surgeries in patients who require ongoing adenosine diphosphate receptor blockade. PMID- 27677506 TI - Protein Design for Nanostructural Engineering: General Aspects. AB - This chapter aims to introduce the main challenges in the field of protein design for engineering of nanostructures and functional materials. First, we introduce proteins and illustrate the key characteristics that open many possibilities for the use of proteins in nanotechnology. Then, we describe the current state of the art of nanopatterning techniques and the actual needs of the emerging field of nanotechnology to develop new tools in order to achieve precise control and manipulation of elements at the nanoscale. In this sense, the increasing knowledge of protein science and advances in protein design allow to tackle current challenges such as the design of nanodevices, nanopatterned surfaces, and nanomachines. This book highlights the recent progresses of protein nanotechnology over the last decade and emphasizes the power of protein engineering through illustrative examples of protein based-assemblies and their potential applications. PMID- 27677507 TI - Designed Protein Origami. AB - Proteins are highly perfected natural molecular machines, owing their properties to the complex tertiary structures with precise spatial positioning of different functional groups that have been honed through millennia of evolutionary selection. The prospects of designing new molecular machines and structural scaffolds beyond the limits of natural proteins make design of new protein folds a very attractive prospect. However, de novo design of new protein folds based on optimization of multiple cooperative interactions is very demanding. As a new alternative approach to design new protein folds unseen in nature, folds can be designed as a mathematical graph, by the self-assembly of interacting polypeptide modules within the single chain. Orthogonal coiled-coil dimers seem like an ideal building module due to their shape, adjustable length, and above all their designability. Similar to the approach of DNA nanotechnology, where complex tertiary structures are designed from complementary nucleotide segments, a polypeptide chain composed of a precisely specified sequence of coiled-coil forming segments can be designed to self-assemble into polyhedral scaffolds. This modular approach encompasses long-range interactions that define complex tertiary structures. We envision that by expansion of the toolkit of building blocks and design strategies of the folding pathways protein origami technology will be able to construct diverse molecular machines. PMID- 27677508 TI - Two-Dimensional Peptide and Protein Assemblies. AB - Two-dimensional nanoscale assemblies (nanosheets) represent a promising structural platform to arrange molecular and supramolecular substrates with precision for integration into devices. This nanoarchitectonic approach has gained significant traction over the last decade, as a general concept to guide the fabrication of functional nanoscale devices. Sequence-specific biomolecules, e.g., peptides and proteins, may be considered excellent substrates for the fabrication of two-dimensional nanoarchitectonics. Molecular level instructions can be encoded within the sequence of monomers, which allows for control over supramolecular structure if suitable design principles could be elaborated. Due to the complexity of interactions between protomers, the development of principles aimed toward rational design of peptide and protein nanosheets is at a nascent stage. This review discusses the known two-dimensional peptide and protein assemblies to further our understanding of how to control the arrangement of molecules in two-dimensions. PMID- 27677509 TI - Designed Repeat Proteins as Building Blocks for Nanofabrication. AB - This chapter will focus on the description of protein-based nanostructures. How proteins can be used as molecular units in order to generate complex materials and structures? What are the key aspects to achieve defined final properties, including shape, stability, function, and order at different length scales by modifying the protein sequence at the modular level?As described in other chapters of the book, we will review the basic concepts and the latest achievements in protein engineering toward nanotechnological applications. Particularly in this chapter the main focus will be on a particular type of proteins, repeat proteins. Because of their modular nature, these proteins are better suited to be used as building blocks than other protein scaffolds. First, we describe general concepts of the protein-based assemblies. Then we introduce repeat proteins and describe the properties that will impact their use in nanotechnology. In particular, we focus on a system based on a synthetic protein, the consensus tetratricopeptide repeat (CTPR). We review recent works from other groups and our group in which the potential of these repeat protein scaffolds is exploited for the fabrication of different protein assemblies, and as biomolecular templates to arrange different molecules and nanoscale objects. PMID- 27677510 TI - Assembly, Engineering and Applications of Virus-Based Protein Nanoparticles. AB - Viruses and their protein capsids can be regarded as biologically evolved nanomachines able to perform multiple, complex biological functions through coordinated mechano-chemical actions during the infectious cycle. The advent of nanoscience and nanotechnology has opened up, in the last 10 years or so, a vast number of novel possibilities to exploit engineered viral capsids as protein based nanoparticles for multiple biomedical, biotechnological or nanotechnological applications. This chapter attempts to provide a broad, updated overview on the self-assembly and engineering of virus capsids, and on applications of virus-based nanoparticles. Different sections provide outlines on: (i) the structure, functions and properties of virus capsids; (ii) general approaches for obtaining assembled virus particles; (iii) basic principles and events related to virus capsid self-assembly; (iv) genetic and chemical strategies for engineering virus particles; (v) some applications of engineered virus particles being developed; and (vi) some examples on the engineering of virus particles to modify their physical properties, in order to improve their suitability for different uses. PMID- 27677511 TI - Dynamic and Active Proteins: Biomolecular Motors in Engineered Nanostructures. AB - In Nature, proteins perform functions that go well beyond controlled self assembly at the nano scale. They are the principal components of diverse "biological machines" that can self-assemble into dynamic aggregates that achieve the cold conversion of chemical energy into motion to realize complex functions involved in cell division, cellular transport and cell motility. Nowadays, we have identified many of the proteins involved in these "molecular machines" and know much about their biochemistry, structure and biophysical behavior. Additionally, we have a rich toolbox of resources to engineer the basic dynamic working units into nanostructures to provide them with motion and the capacity to manipulate, transport, separate or sense single molecules to develop in vitro sensors and bioassays. This chapter summarizes some of the progress made in incorporating bio-molecular motors and dynamic self-organizing proteins into protein based functional nanostructures. PMID- 27677512 TI - Natural Composite Systems for Bioinspired Materials. AB - From a relatively limited selection of base materials, nature has steered the development of truly remarkable materials. The simplest and often overlooked organisms have demonstrated the ability to manufacture multi-faceted, molecular level hierarchical structures that combine mechanical properties rarely seen in synthetic materials. Indeed, these natural composite systems, composed of an array of intricately arranged and functionally relevant organic and inorganic substances serve as inspiration for materials design. A better understanding of these composite systems, specifically at the interface of the hetero-assemblies, would encourage faster development of environmentally friendly "green" materials with molecular level specificities. PMID- 27677513 TI - Protein-Based Hydrogels for Tissue Engineering. AB - The tunable mechanical and structural properties of protein-based hydrogels make them excellent scaffolds for tissue engineering and repair. Moreover, using protein-based components provides the option to insert sequences associated with promoting both cellular adhesion to the substrate and overall cell growth. Protein-based hydrogel components are appealing for their structural designability, specific biological functionality, and stimuli-responsiveness. Here we present highlights in the field of protein-based hydrogels for tissue engineering applications including design requirements, components, and gel types. PMID- 27677514 TI - Design of Self-Assembling Protein-Polymer Conjugates. AB - Protein-polymer conjugates are of particular interest for nanobiotechnology applications because of the various and complementary roles that each component may play in composite hybrid-materials. This chapter focuses on the design principles and applications of self-assembling protein-polymer conjugate materials. We address the general design methodology, from both synthetic and genetic perspective, conjugation strategies, protein vs. polymer driven self assembly and finally, emerging applications for conjugate materials. By marrying proteins and polymers into conjugated bio-hybrid materials, materials scientists, chemists, and biologists alike, have at their fingertips a vast toolkit for material design. These inherently hierarchical structures give rise to useful patterning, mechanical and transport properties that may help realize new, more efficient materials for energy generation, catalysis, nanorobots, etc. PMID- 27677515 TI - Design of Redox-Active Peptides: Towards Functional Materials. AB - In nature, the majority of processes that occur in the cell involve the cycling of electrons and protons, changing the reduction and oxidation state of substrates to alter their chemical reactivity and usefulness in vivo. One of the most relevant examples of these processes is the electron transport chain, a series of oxidoreductase proteins that shuttle electrons through well-defined pathways, concurrently moving protons across the cell membrane. Inspired by these processes, researchers have sought to develop materials to mimic natural systems for a number of applications, including fuel production. The most common cofactors found in proteins to carry out electron transfer are iron sulfur clusters and porphyrin-like molecules. Both types have been studied within natural proteins, such as in photosynthetic machinery or soluble electron carriers; in parallel, an extensive literature has developed over recent years attempting to model and study these cofactors within peptide-based materials. This chapter will focus on major designs that have significantly advanced the field. PMID- 27677516 TI - S-Layer-Based Nanocomposites for Industrial Applications. AB - This chapter covers the fundamental aspects of bacterial S-layers: what are S layers, what is known about them, and what are their main features that makes them so interesting for the production of nanostructures. After a detailed introduction of the paracrystalline protein lattices formed by S-layer systems in nature the chapter explores the engineering of S-layer-based materials. How can S layers be used to produce "industry-ready" nanoscale bio-composite materials, and which kinds of nanomaterials are possible (e.g., nanoparticle synthesis, nanoparticle immobilization, and multifunctional coatings)? What are the advantages and disadvantages of S-layer-based composite materials? Finally, the chapter highlights the potential of these innovative bacterial biomolecules for future technologies in the fields of metal filtration, catalysis, and bio functionalization. PMID- 27677517 TI - Protein Design for Nanostructural Engineering: Concluding Remarks and Future Directions. AB - This final chapter aims to summarize the main conclusions of the book and to point to possible directions for further research in the field of protein design for nanostructural engineering. Even though this research field is still at its infancy, multidisciplinary research efforts in the design of synthetic protein based nanostructures and functional materials have resulted in significant progress. The chapters in this book cover several selected examples of the most recent advances concerning the use of proteins and peptides as building blocks for the fabrication of architectures and functional nanostructures, assemblies, and materials. Here, we provide a general overview of the strategies that can be employed to prepare functional protein-based nanostructures, and nanostructured materials and devices. Finally, we highlight some of the main aspects to be considered by the research community to set the path for the near future developments. PMID- 27677518 TI - Golden Eagle fatalities and the continental-scale consequences of local wind energy generation. AB - Renewable energy production is expanding rapidly despite mostly unknown environmental effects on wildlife and habitats. We used genetic and stable isotope data collected from Golden Eagles (Aquila chrysaetos) killed at the Altamont Pass Wind Resource Area (APWRA) in California in demographic models to test hypotheses about the geographic extent and demographic consequences of fatalities caused by renewable energy facilities. Geospatial analyses of delta2 H values obtained from feathers showed that >=25% of these APWRA-killed eagles were recent immigrants to the population, most from long distances away (>100 km). Data from nuclear genes indicated this subset of immigrant eagles was genetically similar to birds identified as locals from the delta2 H data. Demographic models implied that in the face of this mortality, the apparent stability of the local Golden Eagle population was maintained by continental-scale immigration. These analyses demonstrate that ecosystem management decisions concerning the effects of local-scale renewable energy can have continental-scale consequences. PMID- 27677520 TI - Introduction: Nanoparticle Chemistry. PMID- 27677519 TI - Microsimulation Modeling of Coronary Heart Disease: Maximizing the Impact of Nonprofit Hospital-Based Interventions. AB - We use microsimulation to forecast changes in coronary heart disease (CHD) among adults 45 or above over a 20-year time horizon in Los Angeles County (N = 3.4 million), a county with 12 635 CHD deaths in 2010. We simulate individuals' life course and calibrate CHD trends to observed trends in the past. Using the Health Forecasting Community Health Simulation Model, we simulate CHD prevalence and CHD mortality in 2 CHD prevention scenarios: (1) "comprehensive hypertension intervention" and (2) "gradual reduction of the average adult body mass index back to the year 2000 level." We use microsimulation methodology so that nonprofit hospitals can easily use our model to forecast intervention results in their specific hospital catchment area. Our baseline model (without intervention) forecasts an increase in CHD prevalence that will reach 13.01% among those 45+ in Los Angeles County in 2030. Under scenario 1, the increase in CHD prevalence is slower (12.47% in 2030), and the prevalence in scenario 2 reaches 12.83% in 2030. The baseline scenario projects a number of 21 300 CHD deaths in 2030, whereas there will be 20 070 CHD deaths under scenario 1 and 20 970 CHD deaths under scenario 2. At the population level, the CHD mortality outcome, as compared with the metric of CHD prevalence, might be more sensitive to preventive lifestyle interventions. Both CHD prevalence and CHD mortality might be more sensitive to the hypertension intervention than to the obesity reduction in the time horizon of 20 years. PMID- 27677521 TI - Spectroscopic and Device Aspects of Nanocrystal Quantum Dots. AB - The field of nanocrystal quantum dots (QDs) is already more than 30 years old, and yet continuing interest in these structures is driven by both the fascinating physics emerging from strong quantum confinement of electronic excitations, as well as a large number of prospective applications that could benefit from the tunable properties and amenability toward solution-based processing of these materials. The focus of this review is on recent advances in nanocrystal research related to applications of QD materials in lasing, light-emitting diodes (LEDs), and solar energy conversion. A specific underlying theme is innovative concepts for tuning the properties of QDs beyond what is possible via traditional size manipulation, particularly through heterostructuring. Examples of such advanced control of nanocrystal functionalities include the following: interface engineering for suppressing Auger recombination in the context of QD LEDs and lasers; Stokes-shift engineering for applications in large-area luminescent solar concentrators; and control of intraband relaxation for enhanced carrier multiplication in advanced QD photovoltaics. We examine the considerable recent progress on these multiple fronts of nanocrystal research, which has resulted in the first commercialized QD technologies. These successes explain the continuing appeal of this field to a broad community of scientists and engineers, which in turn ensures even more exciting results to come from future exploration of this fascinating class of materials. PMID- 27677522 TI - The paramedian supracerebellar transtentorial approach to the posterior fusiform gyrus. AB - BACKGROUND: The posterior fusiform gyrus lies in a surgically challenging region. Several approaches have been described to access this anatomical area. The paramedian supracerebellar transtentorial (SCTT) approach benefits from minimal disruption of normal neurovascular tissue. The aim of this study was to demonstrate its application to access the posterior fusiform gyrus. METHODS: Three brains and six cadaveric heads were examined. A stepwise dissection of the SCTT approach to the posterior fusiform gyrus was performed. Local cortical anatomy was studied. The operability score was applied for comparative analysis on surgical anatomy. RESULTS: The major posterior landmark used to identify the fusiform gyrus with respect to the medial occipitotemporal gyrus was the collateral sulcus, which commonly bifurcated at its caudal extent. Compared with other surgical approaches addressed to access the region, SCTT demonstrated the best operability in terms of maneuverability arc. Favorable tentorial anatomy is the only limiting factor. CONCLUSIONS: The supracerebellar transtentorial approach is able to provide access to the posterior fusiform gyrus via a minimally disruptive, anatomic, microsurgical corridor. PMID- 27677523 TI - 5-ALA fluorescence applied to glioneuronal tumors. PMID- 27677524 TI - Intraspecific variation in an Ediacaran skeletal metazoan: Namacalathus from the Nama Group, Namibia. AB - Namacalathus hermanastes is one of the oldest known skeletal metazoans, found in carbonate settings of the terminal Ediacaran (~550-541 million years ago [Ma]). The palaeoecology of this widespread, goblet-shaped, benthic organism is poorly constrained yet critical for understanding the dynamics of the earliest metazoan communities. Analysis of in situ assemblages from the Nama Group, Namibia (~548 541 Ma), shows that Namacalathus exhibited size variation in response to differing water depths, hydrodynamic conditions and substrate types. In low energy, inner ramp environments, Namacalathus attains the largest average sizes but grew in transient, loosely aggregating, monospecific aggregations attached to microbial mats. In high-energy mid-ramp reefs, Namacalathus spatially segregated into different palaeoecological habitats with distinct size distributions. In outer ramp environments, individuals were small and formed patchy, dense, monospecific aggregations attached to thin microbial mats. Asexual budding is common in all settings. We infer that variations in size distribution in Namacalathus reflect differences in habitat heterogeneity and stability, including the longevity of mechanically stable substrates and oxic conditions. In the Nama Group, long-lived skeletal metazoan communities developed within topographically heterogeneous mid-ramp reefs, which provided diverse mechanically stable microbial substrates in persistently oxic waters, while inner and outer ramp communities were often ephemeral, developing during fleeting episodes of either oxia and/or substrate stability. We conclude that Namacalathus, which forms a component of these communities in the Nama Group, was a generalist that adapted to various palaeoecological habitats within a heterogeneous ecosystem landscape where favourable conditions persisted, and was also able to opportunistically colonise transiently hospitable environments. These early skeletal metazoans colonised previously unoccupied substrates in thrombolitic reefs and other microbial carbonate settings, and while they experienced relatively low levels of interspecific competition, they were nonetheless adapted to the diverse environments and highly dynamic redox conditions present in the terminal Ediacaran. PMID- 27677525 TI - 15-Methylene-Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia. AB - Recent studies suggest that leukemia stem cells (LSCs) play a critical role in the initiation, propagation, and relapse of leukemia. Herein we show that (-)-15 methylene-eburnamonine, a derivative of the alkaloid (-)-eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also decreases primary LSC frequency in vitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells. By the use of a novel humanized bone marrow murine model of leukemia (huBM/NSG), it was found to decrease progenitor cell engraftment. PMID- 27677526 TI - Effect of welding fume on heart rate variability among workers with respirators in a shipyard. AB - Welding fume exposure is associated with heart rate variability (HRV) reduction. It is still unknown whether respirator can reduce effect of welding fume on HRV among welding workers in a shipyard. We recruited 68 welding workers with respirator and 52 welding workers without respirator to measure HRV indices, including standard deviation of normal-to-normal intervals (SDNN) and square root of the mean squared differences of successive intervals (r-MSSD) by ambulatory electrocardiographic (ECG). Personal exposure to particulate matter less than or equal to 2.5 MUm in diameter (PM2.5) was measured by a dust monitor. The association between 5-minute mean PM2.5 and log10-transformed HRV indices was analyzed by mixed-effects models. We found 5-minute mean PM2.5 was associated with 8.9% and 10.3% decreases in SDNN and r-MSSD. Effect of PM2.5 on HRV indices was greatest among workers without respirator {SDNN: 12.4% (95% confidence interval = -18.8--6.9); r-MSSD: 14.7% (95% confidence interval = -20.8--8.6)}. Workers with respirator showed slight decreases in HRV indices {SDNN: 2.2% (95% confidence interval = -6.3--1.9); r-MSSD: 4.0% (95% confidence interval = -6.4- 1.6)}. We conclude that respirator use reduces the effect of PM2.5 exposure on HRV among workers performing welding in a shipyard. PMID- 27677527 TI - Evaluation of brand names of medicines: linguistic and format issues. AB - OBJECTIVES: Focusing on the shape of brand names of medicines in the Portuguese market, the aims of this study were: to evaluate the number of words, syllables and letters, to identify the combinations of letters that are not found in Portuguese words and to characterize the use of capital letters in these names. METHODS: A descriptive study was conducted using 474 randomized brand names of medicines, approximately 25% of all over-the-counter and prescribed medicines available in Portugal. The number of words, syllables and letters was automatically determined with a dedicated software. The combinations of letters that are not found in Portuguese and the use of capital letters were quantified through visual inspection. KEY FINDINGS: The 474 names were formed by 615 words. 74.5% of the words comprised three or less syllables, the most common number of syllables in the Portuguese words (91%). As recommended, 81% (n = 385) names were formed by just one word, 59.2% (n = 281) of the names were composed of 5-8 letters, and 83.1% (n = 394) presented the first letter in capitals or all letters in upper case. Contrary to recommendations, 22% of the names comprised combinations of letters that are not commonly found in Portuguese words. CONCLUSIONS: Given the current readability requirements, some of the Portuguese brand names of medicines should be reduced in length, adapted to the native language or capitalized. Equivalent studies are recommended in other European countries, because many brands of medicines are internationally marketed, while their development and approval should be beyond general marketing rules. PMID- 27677528 TI - Effects of dietary methylmercury on the dopaminergic system of adult fathead minnows and their offspring. AB - Mercury (Hg) is a ubiquitous environmental contaminant and potent neurotoxin, which may be transformed by bacteria in aquatic ecosystems to methylmercury (MeHg), an organic form which bioaccumulates and biomagnifies. Consequently, long lived organisms at the top of the food web are at risk of dietary MeHg exposure, which can be actively transferred from mother to offspring. Exposure during neurodevelopment can lead to serious, irreversible neurological dysfunction, associated with a variety of cognitive and motor abnormalities. At low dietary concentrations, MeHg exposure has been associated with deficits in attention and hyperactivity in multiple species. Pathways associated with cognitive function and motor activity are primarily associated with the dopaminergic system. The present study used a model fish species, Pimephales promelas, to examine the effects of MeHg exposure on dopamine concentrations and monoamine oxidase activity in embryos and adult brains. Adult fatheads were exposed for 30 d to either a control or a treated diet (0.72 ppm Hg). Embryonic and larval exposures were a result of maternal transfer of dietary MeHg. The authors confirmed hyperactive behaviors in embryos and detected significant changes in embryonic dopamine concentrations. Similar effects on dopamine concentrations were seen in the telencephalon of adult brains. Exposure to MeHg also corresponded with a significant decrease in monoamine oxidase activity in both embryos and brain tissue. Collectively, these results suggest that current exposure scenarios in North America are sufficient to induce alterations to this highly conserved neurochemical pathway in offspring, which may have adverse effects on fish behavior and cognition. Environ Toxicol Chem 2017;36:1077-1084. (c) 2016 SETAC. PMID- 27677529 TI - Forbidden fruit: human settlement and abundant fruit create an ecological trap for an apex omnivore. AB - Habitat choice is an evolutionary product of animals experiencing increased fitness when preferentially occupying high-quality habitat. However, an ecological trap (ET) can occur when an animal is presented with novel conditions and the animal's assessment of habitat quality is poorly matched to its resulting fitness. We tested for an ET for grizzly (brown) bears using demographic and movement data collected in an area with rich food resources and concentrated human settlement. We derived measures of habitat attractiveness from occurrence models of bear food resources and estimated demographic parameters using DNA mark recapture information collected over 8 years (2006-2013). We then paired this information with grizzly bear mortality records to investigate kill and movement rates. Our results demonstrate that a valley high in both berry resources and human density was more attractive than surrounding areas, and bears occupying this region faced 17% lower apparent survival. Despite lower fitness, we detected a net flow of bears into the ET, which contributed to a study-wide population decline. This work highlights the presence and pervasiveness of an ET for an apex omnivore that lacks the evolutionary cues, under human-induced rapid ecological change, to assess trade-offs between food resources and human-caused mortality, which results in maladaptive habitat selection. PMID- 27677531 TI - Demographic effects of deltamethrin resistance in the Chagas disease vector Triatoma infestans. AB - Triatoma infestans (Heteroptera: Reduviidae) Klug is the main vector of Chagas disease in Latin America. Resistance to deltamethrin was reported in Argentina and recently associated with reproductive and longevity trade-offs. The objectives of the present study were to describe the demographic consequences of deltamethrin resistance in T. infestans and to establish possible target stages for chemical control in susceptible and resistant colonies. A stage-classified matrix model was constructed based on the average stage length for susceptible, resistant and reciprocal matings' progeny. The differences between colonies were analysed by prospective and retrospective analysis. The life table parameters indicated reduced fecundity, fertility and population growth in resistant insects. The retrospective analysis suggested the latter was associated with lower reproductive output and increased fifth-instar nymph stage length. The prospective analysis suggested that the adult stage should be the main target for insecticide control. Although, fifth-instar nymphs should also be targeted when resistance has been detected. The presented results show demographic effects of deltamethrin resistance in T. infestans. While the older stages could be the main targets for chemical control, this approach is impeded by their higher tolerance to insecticides. It is concluded that the different mode of action insecticides would be more effective than a dose increase for the control of deltamethrin resistant T. infestans. PMID- 27677533 TI - Effects of different dietary tryptophan : lysine ratios and sanitary conditions on growth performance, plasma urea nitrogen, serum haptoglobin and ileal histomorphology of weaned pigs. AB - A total of 180 mixed-sex pigs (Duroc * (Yorkshire * Landrace); average initial body weight of 7.36 +/- 0.2 kg) weaned at 21 +/- 1 days were fed corn-soybean meal-wheat-based diets to determine the optimal standardized ileal digestible (SID) tryptophan to lysine ratio (Trp : Lys) in a 2 * 5 factorial arrangement (two sanitary conditions: clean (CL) and unclean (UCL), and five dietary treatments (SID Trp : Lys (16, 18, 20, 22 and 24%)). In each sanitary condition, blood was collected on days 0 and 14 to determine plasma urea nitrogen and on day 14, ileal tissue (one pig per pen) was collected for the measurement of gut morphology. Pigs kept under UCL conditions had lower growth rate (P < 0.05) than under CL conditions. Under CL conditions, the estimated optimal SID Trp : Lys for average daily gain (ADG) was 19.7% whereas under UCL conditions these values were 20.5% and 19.0% for ADG and gain-to-feed ratio, respectively. Under CL conditions, increasing SID Trp : Lys reduced (linear, P = 0.05) plasma urea nitrogen concentration but had no effect (P > 0.10) on villous height (VH), crypt depth ( CD) and VH : CD. In conclusion, an SID Trp : Lys to optimize ADG for pigs raised under UCL conditions was higher (4%) than CL conditions. PMID- 27677532 TI - Doublecortin-like kinase 1-positive enterocyte - a new cell type in human intestine. AB - Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated kinase. In murine intestine, DCLK1 marks tuft cells with characteristic microvilli, features of neuroendocrine cells and also quiescent stem cell-like properties. The occurrence and pathological role of DCLK1-positive cells in human intestinal mucosa is unknown. We analysed DCLK1 expression in healthy duodenal, jejunal and colorectal mucosa samples (n = 35), and in duodenal specimens from patients with coeliac disease (n = 20). The samples were immunohistochemically double-stained with DCLK1, and synaptophysin, chromogranin A and Ki-67. Ultrastructure of DCLK1 expressing duodenal cells was assessed using correlative light and electron microscopy. DCLK1 expression was seen in about 1% of epithelial cells diffusely scattered through the intestinal epithelium. Electron microscopy showed that the duodenal DCLK1-positive cells had short apical microvilli similar to neighbouring enterocytes and cytoplasmic granules on the basal side. DCLK1-positive cells were stained with synaptophysin. The number of DCLK1-positive cells was decreased in villus atrophy in coeliac disease. Our findings indicate that in human intestinal epithelium, DLCK1-positive cells form a subpopulation of non-proliferating neuroendocrine cells with apical brush border similar to that in enterocytes, and their number is decreased in untreated coeliac disease. PMID- 27677534 TI - Single Electron Gating of Topological Insulators. AB - The effective gating of topological insulators is demonstrated, through the coupling of molecules to their surface. By using electric fields, they allow for dynamic control of the interface charge state by adding or removing single electrons. This process creates a robust transconductance bistability resembling a single-electron transistor. These findings make hybrid molecule/topological interfaces functional elements while at the same time pushing miniaturization to its ultimate limit. PMID- 27677536 TI - Understanding empirical therapeutics in systemic sclerosis gastrointestinal tract disease. PMID- 27677535 TI - Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury. AB - Cell death is an important biological process that is believed to have a central role in intestinal ischaemia/reperfusion (I/R) injury. While the apoptosis inhibition is pivotal in preventing intestinal I/R, how necrotic cell death is regulated remains unknown. Necroptosis represents a newly discovered form of programmed cell death that combines the features of both apoptosis and necrosis, and it has been implicated in the development of a range of inflammatory diseases. Here, we show that receptor-interacting protein 1/3 (RIP1/3) kinase and mixed lineage kinase domain-like protein recruitment mediates necroptosis in a rat model of ischaemic intestinal injury in vivo. Furthermore, necroptosis was specifically blocked by the RIP1 kinase inhibitor necrostatin-1. In addition, the combined treatment of necrostatin-1 and the pan-caspase inhibitor Z-VAD acted synergistically to protect against intestinal I/R injury, and these two pathways can be converted to one another when one is inhibited. In vitro, necrostatin-1 pre-treatment reduced the necroptotic death of oxygen-glucose deprivation challenged intestinal epithelial cell-6 cells, which in turn dampened the production of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-1beta), and suppressed high-mobility group box-1 (HMGB1) translocation from the nucleus to the cytoplasm and the subsequent release of HMGB1 into the supernatant, thus decreasing the activation of Toll-like receptor 4 and the receptor for advanced glycation end products. Collectively, our study reveals a robust RIP1/RIP3-dependent necroptosis pathway in intestinal I/R induced intestinal injury in vivo and in vitro and suggests that the HMGB1 signalling is highly involved in this process, making it a novel therapeutic target for acute ischaemic intestinal injury. PMID- 27677537 TI - Trachyonychia in juvenile dermatomyositis: nail as a mirror to disease activity. PMID- 27677538 TI - Effects of seasonality and a daily photo-protection upon some facial signs of Chinese women. AB - OBJECTIVES: These were two-fold: (i) to record through standardized pictures, the possible changes in 31 facial signs induced, in a 6-month period, by the periodical shift from winter to summer in a group of 43 Chinese women and (ii) to appraise the preventive effects of a strong photo-protective product, daily applied to the faces of an additional group (N = 40) of women of same age-range and presenting same severities of facial signs in winter. METHODS: Facial signs (structural and pigmentation-related) were scored in blind by a panel of 12 experts from photographs taken under standard conditions. Scorings were performed under specific scales as established by a previously published referential Skin Aging Atlas, Volume 2, Asian Type. RESULTS: A significant seasonal impact was found for more than 60% of facial signs, that is presenting a higher severity in summer in the unprotected group. Some changes are of a low or subtle extent, whereas some others show significant amplitudes. The latter comprise eight signs, among the 31, that became, far above scoring threshold, indeed affected during this 6-month period. The observed changes in six of these eight signs, in majority related to pigmentation, appeared efficiently alleviated in the photo protected group. CONCLUSION: The shift from winter to summer exposure is confirmed in altering some facial pigmented signs among Chinese women. Such changes appear much alleviated by a daily strong photo-protective regimen. PMID- 27677539 TI - Intrahepatic Cholestasis of Pregnancy in Women With Twin Pregnancy. AB - The aim of the present work was to determine maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP) in twin pregnancies. All twin pregnancies delivered above 28 gestational weeks in West China Second University Hospital from January 2013 to May 2015 were included. Data on maternal demographics and obstetric complications together with fetal outcomes were collected. The risk of adverse maternal and fetal outcomes were determined in relation to ICP by crude odds ratios (OR) and adjusted ORs (aOR) with 95% confidence intervals (CI). Subgroup analysis concentrated on the effect of assisted reproductive technology (ART), ICP severity, and onset time. A total of 1,472 twin pregnancies were included, of which 362 were cholestasis patients and 677 were conceived by ART. Higher rates of preeclampsia (aOR 1.96; 95% CI 1.35, 2.85), meconium-stained amniotic fluid (aOR 3.10; 95% CI 2.10, 4.61), and preterm deliveries (aOR 3.20; 95% CI 2.35, 4.37) were observed in ICP patients. Subgroup analysis revealed higher incidences of adverse outcomes in severe and early onset ICP groups. In conclusion, adverse maternal and fetal outcomes were strongly associated with ICP in twin patients. Active management and close antenatal monitoring are needed, especially in the early onset and severe groups. PMID- 27677541 TI - Immune checkpoint inhibitors in Hodgkin and non-Hodgkin lymphoma: how they work and when to use them. PMID- 27677540 TI - Development and evaluation of an in-house single step loop-mediated isothermal amplification (SS-LAMP) assay for the detection of Mycobacterium tuberculosis complex in sputum samples from Moroccan patients. AB - BACKGROUND: Tuberculosis (TB) is a major global health problem and remains the leading cause of morbidity and mortality in developing countries. Routinely used TB diagnostic methods, in most endemic areas, are time-consuming, often less sensitive, expensive and inaccessible to most patients. Therefore, there is an urgent need for the development of early, easy to use and effective diagnosis tools of TB, which can be effectively integrated into resource limited settings, to anticipate the early treatment and limit further spread of the disease. Over the last decade, Loop-mediated isothermal amplification (LAMP) assays have become a powerful tool for rapid diagnosis of infectious diseases because of the simplicity of device requirements. Indeed, LAMP is a simple, quick and cost effective Isothermal Nucleic Acid Amplification diagnostic test (INAAT) that has the potential to be used in TB endemic settings of resource-poor countries. METHODS: In the present study, we have developed a simple and rapid TB molecular diagnostic test using a Single-Step Loop-mediated isothermal DNA amplification (SS-LAMP) method for the detection of Mycobacterium tuberculosis complex (MTBC) strains, with a simplified sample preparation procedure, eliminating DNA extraction prior to LAMP amplification, DNA initial denaturation and enzymatic inactivation steps during the amplification process. To perform our in-house SS LAMP assay, a set of six specific primers was specifically designed to recognize eight distinct regions on the MTBC species-specific repetitive insertion sequence 6110 (IS6110). The amplification of the targeted DNA was carried out under isothermal conditions at 65 degrees C within 1 h. Our protocol was firstly optimized using 60 of confirmed MTBC isolates and a recombinant pGEMeasy-IS6110 vector for sensitivity testing. Thereafter, the assay was evaluated on liquefied sputum specimens collected from 157 Moroccan patients suspected of having TB. RESULTS: Our SS-LAMP developed assay was able to detect MTBC DNA directly from liquefied sputum samples without any prior DNA extraction, denaturation nor the final enzymatic inactivation step. When compared to routinely used Lowenstein Jensen (LJ) Culture method, our SS-LAMP assay is rapid and showed specificity and sensitivity of 99.14 % and 82.93 % respectively which are within the international standards. In addition, the limit of detection of our assay was found to be as little as 10 copies of bacterial DNA. CONCLUSION: To our knowledge, this is the first study using a single step LAMP (SS-LAMP) procedure as a rapid, easy to perform and cost effective testing for TB early detection. This innovative assay could be suitable for low-income countries with restricted health equipment facilities. PMID- 27677542 TI - A giant leap in the development of nurse practitioners in Taiwan: From statute to regulation. AB - BACKGROUND AND PURPOSE: The purpose of the article is to clarify and describe nurse practitioner (NP) scope-of-practice regulations, including the process of establishing the regulations, and the concepts of supervision, collaboration, and protocol as well as to illustrate the positive impact of NPs in Taiwan. METHODS: A literature review was conducted to understand physician involvement, NP scope of practice, and written practice protocol. A simultaneous review of authoritative regulations, related to local statutes and regulations in the United States, was conducted. CONCLUSIONS: After the Legislative Yuan approved an amendment of NP scope of practice on August 5, 2014, NPs can practice legally, with statute protection. These scope-of-practice regulations, developed by the Ministry of Health and Welfare, and the concept of physician supervision and written practice protocol represent a significant advance for NPs in Taiwan. IMPLICATIONS FOR PRACTICE: We believe that establishing NP scope-of-practice regulations can result in the optimal development of this new role and improve quality of care. By sharing our milestones, from statute to regulations of the NP scope of practice, other countries that are in the process of developing the NP role can draw on our experience to establish their local regulations. PMID- 27677543 TI - New insights into the interaction of proteins and disaccharides-The effect of pH and concentration. AB - To gain new insights into the interaction of proteins and disaccharides, we investigated the hydrodynamic radii, RhProt, of lysozyme molecules in solution and in a ternary protein-sugar-water system by PFG-NMR. Our approach is based on the assumption that the anhydrobiotic properties of disaccharides like trehalose are based on aggregation of sugar molecules to the proteins, i.e., accumulation of sugar molecules close to the protein, and that this process can be investigated by the experimentally detectable RhProt value of the protein. The Rh values are calculated from the experimentally determined diffusion coefficients and the application of a viscosity correction using the inert molecule dioxane as an internal viscosity reference. The experiments were performed as a function of sugar concentration, the overall particle concentration and the pH value. We investigated the disaccharides trehalose and sucrose, mainly for the reason that trehalose has well know cryptobiotic properties while sucrose, which is similar in size and structure, lacks these properties. The results show the formation of a protective sugar shell around the proteins over a wider range of concentrations and pH values in the case of trehalose. PMID- 27677544 TI - Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats. AB - CONTEXT: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties. OBJECTIVE: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14th day of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to l methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28th-32nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done. RESULTS: HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 +/- 2.36 versus 10.73 +/- 1.26 MUmoles/mg), brain lipid peroxidation (15.25 +/- 1.65 versus 6.18 +/- 0.74 nM/mg), serum homocysteine (Hcy) (22.37 +/- 0.30 versus 11.01 +/- 1.01 MUg/mL) and serum cholesterol (182.7 +/- 2.15 versus 101.5 +/- 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations. CONCLUSION: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity. PMID- 27677545 TI - Prognostic Value of Serum D-Dimer in Noncardioembolic Ischemic Stroke. AB - BACKGROUND: Although D-dimer levels are significantly associated with cardioembolic infarction, the significance of D-dimer levels in relation to the severity and functional outcomes of other stroke subtypes, such as lacunar and large artery atherosclerosis infarction, remains unclear. The purpose of this study was to evaluate whether elevated initial D-dimer levels are significantly and cross-sectionally associated with poor functional outcomes at each time point during a 9-month follow-up period. We also investigated the significance of D dimer levels in longitudinal temporal changes of functional outcomes in these patients. METHODS: We recruited 146 patients with lacunar infarction and 161 patients with large artery atherosclerosis infarction who were consecutively admitted to our hospital after acute stroke. Serum D-dimer levels were evaluated initially and the modified Rankin scale were measured initially and at 1-, 3-, 6 , and 9-month follow-up visits. RESULTS: Patients with higher D-dimer levels had significantly worse initial functional outcomes, and these worse outcomes were maintained throughout the 9-month follow-up period compared with the low D-dimer group. However, regardless of stroke subtype, D-dimer levels did not influence long-term changes in functional outcomes over the 9-month follow-up period. CONCLUSION: This study suggests that elevated D-dimer levels can be used as a surrogate marker for poor functional outcomes only during the acute stage. Further evaluation of serum D-dimer levels could provide a helpful predictive marker for stroke prognosis. PMID- 27677547 TI - Different routes and forms of uterotonics for treatment of retained placenta: a randomized clinical trial. AB - OBJECTIVES: To compare between three different uterotonics (oxytocin, carbetocin and misoprostol) given via three different routes (intraumbilical, intravenous and sublingual, respectively) in reducing the need for manual removal of placenta (MROP). METHODS: A randomized trial for cases with retained placenta 30 min following vaginal delivery. They received intraumbilical oxytocin, intravenous carbetocin or sublingual misoprostol. Main outcome measures were delivery of the placenta within 30 min following drug administration, and need for MROP. Secondary outcome measures were injection to placental delivery time, post delivery hemoglobin, need for blood transfusion or additional uterotonics. RESULTS: The overall success rate was 66.7% (64/96), 71.3% (67/94) and 63.7% (58/91) for oxytocin, carbetocin and misoprostol groups, respectively (p > 0.05). When time needed to achieve placental delivery considered, a significant difference was observed with the shortest time for carbetocin (16.61 +/- 3.76 min), then oxytocin (18.28 +/- 3.34 min) and lastly misoprostol (23.00 +/- 3.38 min) (p <0.001). Again, carbetocin group needed less additional uterotonics to achieve adequate uterine contractions (p <0.001). CONCLUSIONS: Although we aimed to exploit the advantage of certain drug over another, all seemed to have close efficacy but it would be important that further research should highlight availability, cost, ease of administration and storage requirements to determine which agent would best be used in this clinical scenario. PMID- 27677548 TI - Structural Characteristics and Catalytic Mechanism of Bacillus beta-Propeller Phytases. AB - beta-Propeller phytases of Bacillus are unique highly conservative and highly specific enzymes capable of cleaving insoluble phytate compounds. In this review, we analyzed data on the properties of these enzymes, their differences from other phytases, and their unique spatial structures and substrate specificities. We considered influences of different factors on the catalytic activity and thermostability of these enzymes. There are few data on the hydrolysis mechanism of these enzymes, which makes it difficult to analyze their mechanism of action and their final products. We analyzed the available data on hydrolysis by beta propeller phytases of calcium complexes with myo-inositol hexakisphosphate. PMID- 27677546 TI - Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on omega-3 supplementation. AB - Monocyte/macrophages of patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are defective in phagocytosis and degradation amyloid beta1-42 (Abeta1-42), but are improved by omega-3 fatty acids (omega-3s). The hypothesis of this study was that active Abeta1-42 phagocytosis by macrophages prevents brain amyloidosis and thus maintains cognition. We studied the effects of self-supplementation with a drink with omega-3s, antioxidants, and resveratrol on Mini-Mental State Examination (MMSE) scores, macrophage M1M2 phenotype [the ratio of inflammatory cluster of differentiation (CD)54+CD80 and proresolution markers CD163+CD206], and Abeta1-42 phagocytosis in patients initially diagnosed as having MCI or subjective cognitive impairment (SCI). At baseline, the median MMSE score in patients in both the apolipoprotein E (ApoE) epsilon3/epsilon3 and ApoE epsilon3/epsilon4 groups was 26.0 and macrophage Abeta1-42 phagocytosis was defective. The MMSE rate of change increased in the ApoE epsilon3/epsilon3 group a median 2.2 points per year (P = 0.015 compared to 0) but did not change in the ApoE epsilon3/epsilon4 group (P = 0.014 between groups). In the ApoE epsilon3/epsilon3 group, all patients remained cognitively stable or improved; in the ApoE epsilon3/epsilon4 group, 1 recovered from dementia, but 3 lapsed into dementia. The macrophage phenotype polarized in patients bearing ApoE epsilon3/epsilon3 to an intermediate (green zone) M1-M2 type at the rate of 0.226 U/yr, whereas in patients bearing ApoE epsilon3/epsilon4, polarization was negative (P = 0.08 between groups). The baseline M1M2 type in the extreme M1 (red zone) or M2 (white zone) was unfavorable for cognitive outcome. Abeta1-42 phagocytosis increased in both ApoE groups (P = 0.03 in each groups). In vitro, the lipidic mediator resolvin D1 (RvD1) down regulated the M1 type in patients with ApoE epsilon3/epsilon3 but in some patients with epsilon3/epsilon4, paradoxically up-regulated the M1 type. Antioxidant/omega-3/resveratrol supplementation was associated with favorable immune and cognitive responses in ApoE epsilon3/epsilon3 and individual patients bearing ApoE epsilon3/epsilon4, and brings into personalized clinical practice the immune benefits expected from omega-3 mediators called resolvins. The validity of this study is limited by its small size and uncontrolled design.-Famenini, S., Rigali, E. A., Olivera-Perez, H. M., Dang, J., Chang, M T., Halder, R., Rao, R. V., Pellegrini, M., Porter, V., Bredesen, D., Fiala, M. Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on omega-3 supplementation. PMID- 27677549 TI - Neurotoxic Non-proteinogenic Amino Acid beta-N-Methylamino-L-alanine and Its Role in Biological Systems. AB - Secondary metabolites of photoautotrophic organisms have attracted considerable interest in recent years. In particular, molecules of non-proteinogenic amino acids participating in various physiological processes and capable of producing adverse ecological effects have been actively investigated. For example, the non proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is neurotoxic to animals including humans. It is known that BMAA accumulation via the food chain can lead to development of neurodegenerative diseases in humans such as Alzheimer's and Parkinson's diseases as well as amyotrophic lateral sclerosis. Moreover, BMAA can be mistakenly incorporated into a protein molecule instead of serine. Natural sources of BMAA and methods for its detection are discussed in this review, as well as the role of BMAA in metabolism of its producers and possible mechanisms of toxicity of this amino acid in different living organisms. PMID- 27677550 TI - alpha-Tocopheryl Succinate Affects Malignant Cell Viability, Proliferation, and Differentiation. AB - The widespread occurrence of malignant tumors motivates great attention to finding and investigating effective new antitumor preparations. Such preparations include compounds of the vitamin E family. Among them, alpha-tocopheryl succinate (vitamin E succinate (VES)) has the most pronounced antitumor properties. In this review, various targets and mechanisms of the antitumor effect of vitamin E succinate are characterized. It has been shown that VES has multiple intracellular targets and effects, and as a result VES is able to induce apoptosis in tumor cells, inhibit their proliferation, induce differentiation, prevent metastasizing, and inhibit angiogenesis. However, VES has minimal effects on normal cells and tissues. Due to the variety of targets and selectivity of action, VES is a promising agent against malignant neoplasms. More detailed studies in this area can contribute to development of effective and safe chemotherapeutic preparations. PMID- 27677551 TI - Plant Sterols: Diversity, Biosynthesis, and Physiological Functions. AB - Sterols, which are isoprenoid derivatives, are structural components of biological membranes. Special attention is now being given not only to their structure and function, but also to their regulatory roles in plants. Plant sterols have diverse composition; they exist as free sterols, sterol esters with higher fatty acids, sterol glycosides, and acylsterol glycosides, which are absent in animal cells. This diversity of types of phytosterols determines a wide spectrum of functions they play in plant life. Sterols are precursors of a group of plant hormones, the brassinosteroids, which regulate plant growth and development. Furthermore, sterols participate in transmembrane signal transduction by forming lipid microdomains. The predominant sterols in plants are beta-sitosterol, campesterol, and stigmasterol. These sterols differ in the presence of a methyl or an ethyl group in the side chain at the 24th carbon atom and are named methylsterols or ethylsterols, respectively. The balance between 24 methylsterols and 24-ethylsterols is specific for individual plant species. The present review focuses on the key stages of plant sterol biosynthesis that determine the ratios between the different types of sterols, and the crosstalk between the sterol and sphingolipid pathways. The main enzymes involved in plant sterol biosynthesis are 3-hydroxy-3-methylglutaryl-CoA reductase, C24-sterol methyltransferase, and C22-sterol desaturase. These enzymes are responsible for maintaining the optimal balance between sterols. Regulation of the ratios between the different types of sterols and sterols/sphingolipids can be of crucial importance in the responses of plants to stresses. PMID- 27677552 TI - Functional Role of Carbohydrate Residues in Human Immunoglobulin G and Therapeutic Monoclonal Antibodies. AB - Therapeutic monoclonal antibodies (TMA) provide an important means for treating diseases that were previously considered untreatable. Currently more than 40 full size TMAs created primarily based on immunoglobulin G1 are widely used for treating various illnesses. Glycosylation of TMA is among other numerous factors that affect their biological activity, effector functions, immunogenicity, and half-life in the patient's serum. The importance of carbohydrate residues for activity of human serum immunoglobulin and TMA produced in animal cells is considered in this review, with emphasis given to N-glycosylation of the Fc fragment of the antibody. PMID- 27677553 TI - Photosystem II Activity of Wild Type Synechocystis PCC 6803 and Its Mutants with Different Plastoquinone Pool Redox States. AB - To assess the role of redox state of photosystem II (PSII) acceptor side electron carriers in PSII photochemical activity, we studied sub-millisecond fluorescence kinetics of the wild type Synechocystis PCC 6803 and its mutants with natural variability in the redox state of the plastoquinone (PQ) pool. In cyanobacteria, dark adaptation tends to reduce PQ pool and induce a shift of the cyanobacterial photosynthetic apparatus to State 2, whereas illumination oxidizes PQ pool, leading to State 1 (Mullineaux, C. W., and Holzwarth, A. R. (1990) FEBS Lett., 260, 245-248). We show here that dark-adapted Ox(-) mutant with naturally reduced PQ is characterized by slower QA(-) reoxidation and O2 evolution rates, as well as lower quantum yield of PSII primary photochemical reactions (Fv/Fm) as compared to the wild type and SDH(-) mutant, in which the PQ pool remains oxidized in the dark. These results indicate a large portion of photochemically inactive PSII reaction centers in the Ox(-) mutant after dark adaptation. While light adaptation increases Fv/Fm in all tested strains, indicating PSII activation, by far the greatest increase in Fv/Fm and O2 evolution rates is observed in the Ox(-) mutant. Continuous illumination of Ox(-) mutant cells with low-intensity blue light, that accelerates QA(-) reoxidation, also increases Fv/Fm and PSII functional absorption cross-section (590 nm); this effect is almost absent in the wild type and SDH(-) mutant. We believe that these changes are caused by the reorganization of the photosynthetic apparatus during transition from State 2 to State 1. We propose that two processes affect the PSII activity during changes of light conditions: 1) reversible inactivation of PSII, which is associated with the reduction of electron carriers on the PSII acceptor side in the dark, and 2) PSII activation under low light related to the increase in functional absorption cross-section at 590 nm. PMID- 27677554 TI - Binding of Synthetic LKEKK Peptide to Human T-Lymphocytes. AB - The synthetic peptide LKEKK corresponding to sequence 16-20 of human thymosin alpha1 and 131-135 of human interferon-alpha2 was labeled with tritium to specific activity 28 Ci/mol. The [3H]LKEKK bound with high affinity (Kd = 3.7 +/- 0.3 nM) to donor blood T-lymphocytes. Treatment of cells with trypsin or proteinase K did not abolish [3H]LKEKK binding, suggesting the non-protein nature of the peptide receptor. The binding was inhibited by thymosin-alpha1, interferon alpha2, and cholera toxin B subunit (Ki = 2.0 +/- 0.3, 2.2 +/- 0.2, and 3.6 +/- 0.3 nM, respectively). Using [3H]LKEKK, we demonstrated the existence of a non protein receptor common for thymosin-alpha1, interferon-alpha2, and cholera toxin B-subunit on donor blood T-lymphocytes. PMID- 27677555 TI - Effects of Ouabain on Proliferation of Human Endothelial Cells Correlate with Na+,K+-ATPase Activity and Intracellular Ratio of Na+ and K. AB - Side-by-side with inhibition of the Na+,K+-ATPase ouabain and other cardiotonic steroids (CTS) can affect cell functions by mechanisms other than regulation of the intracellular Na+ and K+ ratio ([Na+]i/[K+]i). Thus, we compared the dose- and time-dependences of the effect of ouabain on intracellular [Na+]i/[K+]i ratio, Na+,K+-ATPase activity, and proliferation of human umbilical vein endothelial cells (HUVEC). Treatment of the cells with 1-3 nM ouabain for 24-72 h decreased the [Na+]i/[K+]i ratio and increased cell proliferation by 20-50%. We discovered that the same ouabain concentrations increased Na+,K+-ATPase activity by 25-30%, as measured by the rate of (86)Rb(+) influx. Higher ouabain concentrations inhibited Na+,K+-ATPase, increased [Na+]i/[K+]i ratio, suppressed cell growth, and caused cell death. When cells were treated with low ouabain concentrations for 48 or 72 h, a negative correlation between [Na+]i/[K+]i ratio and cell growth activation was observed. In cells treated with high ouabain concentrations for 24 h, the [Na+]i/[K+]i ratio correlated positively with proliferation inhibition. These data demonstrate that inhibition of HUVEC proliferation at high CTS concentrations correlates with dissipation of the Na+ and K+ concentration gradients, whereas cell growth stimulation by low CTS doses results from activation of Na+,K+-ATPase and decrease in the [Na+]i/[K+]i ratio. PMID- 27677556 TI - Features of Gene Expression of Bacillus pumilus Metalloendopeptidase. AB - Features of gene expression of the secreted Bacillus pumilus metalloendopeptidase belonging to the adamalysin/reprolysin family were investigated. In the regulatory region of the gene, we identified hypothetical binding sites for transcription factors CcpA and TnrA. We found that the expression of the metalloendopeptidase gene is controlled by mechanisms of carbon and nitrogen catabolite repression. In experiments involving nitrogen metabolism regulatory protein mutant strains, we found that the control of the metalloendopeptidase gene expression involves proteins of ammonium transport GlnK and AmtB interacting with the TnrA-regulator. PMID- 27677557 TI - Glutamic Acid - Amino Acid, Neurotransmitter, and Drug - Is Responsible for Protein Synthesis Rhythm in Hepatocyte Populations in vitro and in vivo. AB - Primary cultures of rat hepatocytes were studied in serum-free media. Ultradian protein synthesis rhythm was used as a marker of cell synchronization in the population. Addition of glutamic acid (0.2 mg/ml) to the medium of nonsynchronous sparse cultures resulted in detection of a common protein synthesis rhythm, hence in synchronization of the cells. The antagonist of glutamic acid metabotropic receptors MCPG (0.01 mg/ml) added together with glutamic acid abolished the synchronization effect; in sparse cultures, no rhythm was detected. Feeding rats with glutamic acid (30 mg with food) resulted in protein synthesis rhythm in sparse cultures obtained from the rats. After feeding without glutamic acid, linear kinetics of protein synthesis was revealed. Thus, glutamic acid, a component of blood as a non-neural transmitter, can synchronize the activity of hepatocytes and can form common rhythm of protein synthesis in vitro and in vivo. This effect is realized via receptors. Mechanisms of cell-cell communication are discussed on analyzing effects of non-neural functions of neurotransmitters. Glutamic acid is used clinically in humans. Hence, a previously unknown function of this drug is revealed. PMID- 27677558 TI - NMDA-Receptors Are Involved in Cu2+/Paraquat-Induced Death of Cultured Cerebellar Granule Neurons. AB - Rat cultured cerebellar granule neurons (CGNs) were not sensitive to CuCl2 (1-10 uM, 24 h), whereas paraquat (150 uM) decreased neuronal survival to 79 +/- 3% of control level. Simultaneous treatment of CGNs with paraquat and CuCl2 (2, 5, or 10 uM Cu2+/paraquat) caused significant copper dose-dependent death, lowering their survival to 56 +/- 4, 37 +/- 3, or 16 +/- 2%, respectively, and stimulating elevated production of free radicals in CGNs. Introduction of vitamin E, a non competitive antagonist of NMDA subtype of glutamate receptors (MK-801), and also removal of glutamine from the incubation medium decreased toxicity of Cu2+/paraquat mixture. However, addition of Cu2+ into the incubation medium did not affect CGNs death caused by glutamate. These data emphasize that excessive copper in the brain may trigger oxidative stress, which in turn results in release of glutamate, overstimulation of glutamate receptors, and neuronal death. PMID- 27677559 TI - Temporal Scaling of Age-Dependent Mortality: Dynamics of Aging in Caenorhabditis elegans Is Easy to Speed Up or Slow Down, but Its Overall Trajectory Is Stable. AB - The dynamics of aging is often described by survival curves that show the proportion of individuals surviving to a given age. The shape of the survival curve reflects the dependence of mortality on age, and it varies greatly for different organisms. In a recently published paper, Stroustrup and coauthors ((2016) Nature, 530, 103-107) showed that many factors affecting the lifespan of Caenorhabditis elegans do not change the shape of the survival curve, but only stretch or compress it in time. Apparently, this means that aging is a programmed process whose trajectory is difficult to change, although it is possible to speed it up or slow it down. More research is needed to clarify whether the "rule of temporal scaling" is applicable to other organisms. A good indicator of temporal scaling is the coefficient of lifespan variation: similar values of this coefficient for two samples indicate similar shape of the survival curves. Preliminary results of experiments on adaptation of Drosophila melanogaster to unfavorable food show that temporal scalability of survival curves is sometimes present in more complex organisms, although this is not a universal rule. Both evolutionary and environmental changes sometimes affect only the average lifespan without changing the coefficient of variation (in this case, temporal scaling is present), but often both parameters (i.e. both scale and shape of the survival curve) change simultaneously. In addition to the relative stability of the coefficient of variation, another possible argument in favor of genetic determination of the aging process is relatively low variability of the time of death, which is sometimes of the same order of magnitude as the variability of timing of other ontogenetic events, such as the onset of sexual maturation. PMID- 27677560 TI - Comparison of Emergency Department Wait Times in Adults with Sickle Cell Disease Versus Other Painful Etiologies. AB - Sickle cell disease is characterized by intermittent painful crises often requiring treatment in the emergency department (ED). Past examinations of time to-provider (TTP) in the ED for patients with sickle cell disease demonstrated that these patients may have longer TTP than other patients. Here, we examine TTP for patients presenting for emergency care at a single institution, comparing patients with sickle cell disease to both the general population and to those with other painful conditions, with examination of both institutional and patient factors that might affect wait times. Our data demonstrated that at our institution patients with sickle cell disease have a slightly longer average TTP compared to the general ED population (+16 min.) and to patients with other painful conditions (+4 min.) However, when confounding factors were considered, there was no longer a significant difference between TTP of patients with sickle cell disease and the general population nor between patients with sickle cell disease and those with other painful conditions. Multivariate analyses demonstrated that gender, race, age, high utilizer status, fast track use, time of presentation, acuity and insurance type, were all independently associated with TTP, with acuity, time of presentation and use of fast track having the greatest influence. We concluded that the longer TTP observed in patients with sickle cell disease can at least partially be explained by institutional factors such as the use of fast track protocols. Further work to reduce TTP for sickle cell disease and other patients is needed to optimize care. PMID- 27677561 TI - Statin use and risk of cholecystectomy - A case-control analysis using Swiss claims data. AB - OBJECTIVES: Using claims data from the Helsana Group, a large Swiss health insurance provider, we examined the association between statin use and the risk of cholecystectomy in a case-control analysis. METHODS: We identified 2,200 cholecystectomy cases between 2013 and 2014 and matched 4 controls to each case on age, sex, index date and canton. We categorized statin users into current or past users (last prescription <= 180 or > 180 days before the index date, respectively) and classified medication use by duration based on number of prescriptions before the index date. We applied conditional logistic regression analyses to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and adjusted the analyses for history of cardiovascular diseases and for use of estrogens, fibrates and other lipid-lowering agents. RESULTS: The adjusted OR (aOR) for cholecystectomy was 0.85 (95% CI: 0.74, 0.99) for current statin users compared to non-users. Long-term current statin use (5-19 prescriptions) was associated with a reduced OR (aOR 0.77, 95% CI: 0.65, 0.92). However, neither short-term current use nor past statin use affected the risk of cholecystectomy. CONCLUSIONS: The study supports the previously raised hypothesis that long-term statin use reduces the risk of cholecystectomy. PMID- 27677562 TI - Serum urate at trial entry and ALS progression in EMPOWER. AB - Our objective was to determine whether serum urate predicts ALS progression. A study population comprised adult participants of EMPOWER (n = 942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. We measured outcomes by combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results showed that in females there was not a significant relation between urate and outcomes. In males, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend = 0.04; and hazard ratio for death was 0.60 with p for trend = 0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dl) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval 0.47-0.95). In conclusion, these findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate. PMID- 27677563 TI - Ubiquitin-associated domain of MARK4 provides stability at physiological pH. AB - Microtubule affinity regulating Kinase 4 (MARK4) belongs to the family of AMP activated protein kinase. It phosphorylates microtubule associated proteins at specific sites (Serine in KXGS motifs) in the microtubule-binding repeats. In our previous studies, two constructs, namely, kinase domain with 59 N-terminal residues (residues 1-310) and only kinase domain (residues 59-310) of MARK4 show aggregation at physiological pH. However, these two constructs were stable at extremes of pH conditions. Now the question arises: how is MARK4 stable at physiological pH in-vivo? To answer this question, we have successfully cloned, expressed, and purified UBA-domain along with the kinase domain of MARK4 and performed spectroscopic measurements and activity assays. We observed a pronounced secondary and tertiary structure and ATPase activity in the MARK4 at physiological pH. In conclusion, UBA domain may be important to maintain the structure, stability and activity of MARK4 under physiological conditions. PMID- 27677564 TI - Single Versus Double Lung Retransplantation Does Not Affect Survival Based on Previous Transplant Type. AB - BACKGROUND: Survival following retransplantation with a single lung is worse than after double lung transplant. We sought to characterize survival of patients who underwent lung retransplantation based on the type of their initial transplant, single or double. METHODS: The United Network for Organ Sharing database was queried for adult patients who underwent lung retransplantation from 2005 onward. Patients were excluded if they underwent more than one retransplantation. The patient population was divided into 4 groups based on first followed by second transplant type, respectively: single then single, double then single, double then double, and single then double. Descriptive analysis and Kaplan-Meier survival analysis were performed. A p value less than 0.05 was considered significant. RESULTS: A total of 410 patients underwent retransplantation in the study time period. Overall mean survival for all patients who underwent retransplantation was 1,213 days. Kaplan-Meier survival analysis demonstrated no difference in graft survival between the 4 study groups (p = 0.146). CONCLUSIONS: There was no significant difference in graft survival between recipients of retransplant with single or double lungs when stratified by previous transplant type. These results suggest that when retransplantation is performed, single lung retransplantation should be considered, regardless of previous transplant type, in an effort to maximize organ resources. PMID- 27677565 TI - Improved Functional Results After Minimally Invasive Esophagectomy: Intrathoracic Versus Cervical Anastomosis. AB - BACKGROUND: Both cervical esophagogastric anastomosis (CEA) and intrathoracic esophagogastric anastomosis (IEA) are used to restore gastrointestinal integrity following minimally invasive esophagectomy (MIE). No prospective randomized data on functional outcome, postoperative morbidity, and mortality between these techniques are currently available. METHODS: A comparison was conducted including all consecutive patients with esophageal carcinoma of the distal esophagus or gastroesophageal junction undergoing MIE with CEA or MIE with IEA from October 2009 to July 2014 in 3 high-volume esophageal cancer centers. Functional outcome, postoperative morbidity, and mortality were analyzed. RESULTS: MIE with CEA was performed in 146 patients and MIE with IEA in 210 patients. The incidence of recurrent laryngeal nerve palsy was 14.4% after CEA and 0% after IEA (p < 0.001). Dysphagia, dumping, and regurgitation were reported less frequently after IEA compared with CEA (p < 0.05). Dilatation of benign strictures occurred in 43.8% after CEA and this was 6.2% after IEA (p < 0.001). If a benign stricture was identified, it was dilated a median of 4 times in the CEA group and only once in the IEA group (p < 0.001). Anastomotic leakage for which reoperation was required occurred in 8.2% after CEA and in 11.4% after IEA (not significant). Median ICU stay, hospital stay, in-hospital mortality, 30-day mortality, and 90-day mortality were similar between the groups (not significant). CONCLUSIONS: MIE with IEA was associated with better functional results than MIE with CEA with less dysphagia, less benign anastomotic strictures requiring fewer dilatations, and a lower incidence of recurrent laryngeal nerve palsy. Other postoperative morbidity and mortality did not differ between the groups. PMID- 27677566 TI - Imaging Surveillance After Proximal Aortic Operations: Is it Necessary? AB - BACKGROUND: Current guidelines for imaging surveillance after proximal aortic repair are not evidence based. This study sought to characterize the incidence and causes of reintervention after proximal aortic operations to provide data to guide the frequency and duration of postoperative surveillance. METHODS: Data on all patients undergoing proximal aortic operations (ascending, with or without root, with or without aortic valve replacement, or with or without arch) during a 9-year period (n = 869) at a single institution were prospectively collected. Patients who required reintervention on the proximal or distal aorta were identified and causes for reintervention determined. Planned two-stage repairs and index procedures done at other hospitals were excluded. The primary end point was the time to the first reintervention, and competing-risk Cox regression was used to model reintervention risk. RESULTS: Reinterventions occurred in 4.3% of patients (n = 37), with 48.6% (n = 18) involving the proximal aorta and 51.4% (n = 19) the distal. Median time to reintervention was 2.8 years (interquartile range, 1.5 to 3.6 years). For index aneurysm cases, reintervention for aneurysm of the descending/thoracoabdominal aorta and root were most common. Of the 6 root aneurysms/pseudoaneurysms, 5 (83%) were due to degeneration of a stentless porcine aortic root. For index type A dissections, reintervention for aneurysm of the descending/thoracoabdominal aorta and arch were most common. The mean duration of follow up was 4.2 +/- 2.5 years. The 9-year actuarial freedom from reintervention was 92.9%. Cox regression showed index type A dissection was a significant predictor of time to aortic reintervention (hazard ratio, 2.01; 95% confidence interval, 1.04 to 3.9; p = 0.038). CONCLUSIONS: Reinterventions after proximal aortic operations are uncommon; most occur within 3 years of the index operation and involve the proximal and distal aorta nearly equally. Patients with type A dissection or stentless porcine roots require aggressive surveillance, whereas a more liberal approach is suitable for patients without such risk factors. This strategy may reduce the lifetime radiation burden and health care costs. PMID- 27677568 TI - Oxygen as a driver of gut dysbiosis. AB - Changes in the composition of gut-associated microbial communities may underlie many inflammatory and allergic diseases. However, the processes that help maintain a stable community structure are poorly understood. Here we review topical work elucidating the nutrient-niche occupied by facultative anaerobic bacteria of the family Enterobacteriaceae, whose predominance within the gut associated microbial community is a common marker of dysbiosis. A paucity of exogenous respiratory electron acceptors limits growth of Enterobacteriaceae within a balanced gut-associated microbial community. However, recent studies suggest that the availability of oxygen in the large bowel is markedly elevated by changes in host physiology that accompany antibiotic treatment or infection with enteric pathogens, such as Salmonella serovars or attaching and effacing (AE) pathogens. The resulting increase in oxygen availability, alone or in conjunction with other electron acceptors, drives an uncontrolled luminal expansion of Enterobacteriaceae. Insights into the underlying mechanisms provide important clues about factors that control the balance between the host and its resident microbial communities. PMID- 27677567 TI - The chemical biology of the persulfide (RSSH)/perthiyl (RSS.) redox couple and possible role in biological redox signaling. AB - The recent finding that hydropersulfides (RSSH) are biologically prevalent in mammalian systems has prompted further investigation of their chemical properties in order to provide a basis for understanding their potential functions, if any. Hydropersulfides have been touted as hyper-reactive thiol-like species that possess increased nucleophilicity and reducing capabilities compared to their thiol counterparts. Herein, using persulfide generating model systems, the ability of RSSH species to act as one-electron reductants has been examined. Not unexpectedly, RSSH is relatively easily oxidized, compared to thiols, by weak oxidants to generate the perthiyl radical (RSS.). Somewhat surprisingly, however, RSS. was found to be stable in the presence of both O2 and NO and only appears to dimerize. Thus, the RSSH/RSS. redox couple is readily accessible under biological conditions and since dimerization of RSS. may be a rare event due to low concentrations and/or sequestration within a protein, it is speculated that the general lack of reactivity of individual RSS. species may allow this couple to be utilized as a redox component in biological systems. PMID- 27677569 TI - General continuous-time Markov model of sequence evolution via insertions/deletions: local alignment probability computation. AB - BACKGROUND: Insertions and deletions (indels) account for more nucleotide differences between two related DNA sequences than substitutions do, and thus it is imperative to develop a method to reliably calculate the occurrence probabilities of sequence alignments via evolutionary processes on an entire sequence. Previously, we presented a perturbative formulation that facilitates the ab initio calculation of alignment probabilities under a continuous-time Markov model, which describes the stochastic evolution of an entire sequence via indels with quite general rate parameters. And we demonstrated that, under some conditions, the ab initio probability of an alignment can be factorized into the product of an overall factor and contributions from regions (or local alignments) delimited by gapless columns. RESULTS: Here, using our formulation, we attempt to approximately calculate the probabilities of local alignments under space homogeneous cases. First, for each of all types of local pairwise alignments (PWAs) and some typical types of local multiple sequence alignments (MSAs), we numerically computed the total contribution from all parsimonious indel histories and that from all next-parsimonious histories, and compared them. Second, for some common types of local PWAs, we derived two integral equation systems that can be numerically solved to give practically exact solutions. We compared the total parsimonious contribution with the practically exact solution for each such local PWA. Third, we developed an algorithm that calculates the first-approximate MSA probability by multiplying total parsimonious contributions from all local MSAs. Then we compared the first-approximate probability of each local MSA with its absolute frequency in the MSAs created via a genuine sequence evolution simulator, Dawg. In all these analyses, the total parsimonious contributions approximated the multiplication factors fairly well, as long as gap sizes and branch lengths are at most moderate. Examination of the accuracy of another indel probabilistic model in the light of our formulation indicated some modifications necessary for the model's accuracy improvement. CONCLUSIONS: At least under moderate conditions, the approximate methods can quite accurately calculate ab initio alignment probabilities under biologically more realistic models than before. Thus, our formulation will provide other indel probabilistic models with a sound reference point. PMID- 27677570 TI - Mental Health and Antiretroviral Adherence Among Youth Living With HIV in Rwanda. AB - BACKGROUND AND OBJECTIVES: In Rwanda, significant progress has been made in advancing access to antiretroviral therapy (ART) among youth. As availability of ART increases, adherence is critical for preventing poor clinical outcomes and transmission of HIV. The goals of the study are to (1) describe ART adherence and mental health problems among youth living with HIV aged 10 to 17; and (2) examine the association between these factors among this population in rural Rwanda. METHODS: A cross-sectional analysis was conducted that examined the association of mental health status and ART adherence among youth (n = 193). ART adherence, mental health status, and related variables were examined based on caregiver and youth report. Nonadherence was defined as ever missing or refusing a dose of ART within the past month. Multivariate modeling was performed to examine the association between mental health status and ART adherence. RESULTS: Approximately 37% of youth missed or refused ART in the past month. In addition, a high level of depressive symptoms (26%) and attempt to hurt or kill oneself (12%) was observed in this population of youth living with HIV in Rwanda. In multivariate analysis, nonadherence was significantly associated with some mental health outcomes, including conduct problems (odds ratio 2.90, 95% confidence interval 1.55-5.43) and depression (odds ratio 1.02, 95% confidence interval 1.01 1.04), according to caregiver report. A marginally significant association was observed for youth report of depressive symptoms. CONCLUSIONS: The findings suggest that mental health should be considered among the factors related to ART nonadherence in HIV services for youth, particularly for mental health outcomes, such as conduct problems and depression. PMID- 27677571 TI - Alcohol-Related Neurobehavioral Disabilities: Need for Further Definition and Common Terminology. PMID- 27677573 TI - Case Report of Subcutaneous Nodules and Sterile Abscesses Due to Delayed Type Hypersensitivity to Aluminum-Containing Vaccines. AB - Routine childhood immunizations have resulted in great reductions in vaccine preventable infectious diseases. Vaccine-related adverse events, albeit rare, can be of significant consequence. Although anaphylaxis, or type I hypersensitivity, is recognized as a potential reaction after vaccination, delayed type hypersensitivity or type IV reactions are less so. We present a case of persistent subcutaneous nodules and sterile abscesses in the setting of delayed type hypersensitivity to aluminum, confirmed by patch testing and recurrence on re-exposure. We review sources of aluminum in common immunizations, principles for treatment, and strategies for management of future vaccinations for this patient. PMID- 27677572 TI - Neurobehavioral Disorder Associated With Prenatal Alcohol Exposure. AB - Children and adolescents affected by prenatal exposure to alcohol who have brain damage that is manifested in functional impairments of neurocognition, self regulation, and adaptive functioning may most appropriately be diagnosed with neurobehavioral disorder associated with prenatal exposure. This Special Article outlines clinical implications and guidelines for pediatric medical home clinicians to identify, diagnose, and refer children regarding neurobehavioral disorder associated with prenatal exposure. Emphasis is given to reported or observable behaviors that can be identified as part of care in pediatric medical homes, differential diagnosis, and potential comorbidities. In addition, brief guidance is provided on the management of affected children in the pediatric medical home. Finally, suggestions are given for obtaining prenatal history of in utero exposure to alcohol for the pediatric patient. PMID- 27677575 TI - Mitral valve replacement in neonatal endocarditis: time to discuss prevention strategies for Group B streptococcus disease. AB - Group B streptococcus (GBS) is recognised as one of the leading organisms in early-onset neonatal sepsis but is also a cause of late-onset GBS septicaemia, meningitis and rarely, infective endocarditis (IE). We report a case of a healthy term neonate who developed GBS septicaemia and meningitis having presented with parental concern and poor feeding. Subsequent identification and treatment of GBS resulted in the requirement for long-line intravascular access in order to administer antibiotic therapy. One week later, after repeated parental concern and symptoms of shortness of breath, the neonate presented to Accident and Emergency and subsequently a Paediatric Cardiorespiratory Intensive Care Unit where emergency resuscitation procedures were required and diagnosis of severe IE affecting the mitral valve was made. Mitral valve replacement was complicated with significant morbidity and prolonged hospitalisation. An innovative procedure to insert a Melody valve was successful. PMID- 27677574 TI - The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates. AB - BACKGROUND: The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme detoxifying glutathione S-transferase. METHODS: In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed. RESULTS: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression. CONCLUSION: The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine. PMID- 27677576 TI - Euglycaemic ketoacidosis in a postoperative Whipple patient using canaglifozin. AB - SGLT2 inhibitors are a new class of oral antihyperglycaemic agents that have garnered much attention for their attractive efficacy profile in glycaemic control along with the added benefit of weight loss. There has been increasing concern for the risk of euglycaemic (serum glucose 4-8 mmol/L) ketoacidosis with these agents. In the setting of a postoperative patient, the use of these drugs may exacerbate the normal physiological stresses of the body and increase the risk of developing euglycaemic ketoacidosis (euKDA). This case highlights a postoperative patient who was using an SGLT2 inhibitor and developed severe euKDA after a pancreaticoduodenectomy. The goal of this case report was to bring awareness to the possibility of this rare adverse event. In doing so, it may aid in preoperative planning of the diabetic patient and trigger appropriate management for those who develop euKDA. PMID- 27677577 TI - Triple Fundal Coloboma: irregular closure of the embryonic cleft in the optic cup. PMID- 27677578 TI - Barotrauma induced tracheal diverticulum rupture: imaging findings. PMID- 27677579 TI - Risk factors for development of pulmonary arterial hypertension in Australian systemic sclerosis patients: results from a large multicenter cohort study. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with systemic sclerosis (SSc). We sought to determine the incidence, prevalence and risk factors for PAH development in a large Australian SSc cohort. METHODS: PAH was diagnosed on right heart catheterisation (mPAP >25 and PAWP <15 mmHg at rest). Patients with PH secondary to interstitial lung disease (ILD; defined as abnormal HRCT scan and FVC < 60 %) were excluded. Summary statistics, chi-square tests, univariate and multivariable logistic regression along with post-estimation diagnostics were used to determine the associations of different combinations of risk factors with PAH. RESULTS: Among 1579 SSc patients, 8.4 % (132 patients) were diagnosed with PAH over a mean (+/ SD) follow-up of 3.2 (+/-2.5) years. The incidence of PAH in this cohort was 0.7 % per annum. Of these, 68.9 % had limited disease subtype (lcSSc). In multivariable regression analysis, the presence of anti-centromere antibody (ACA) (OR 1.6, 95 % CI 1.1-2.5, p = 0.03), oesphageal stricture (OR 2.0, 95 % CI 1.2 3.3, p = 0.006), calcinosis (OR 1.9, 95 % CI 1.2-2.9, p = 0.003), sicca symptoms (OR 1.6, 95 % CI 1.1-2.5, p = 0.03), mild ILD (OR 2.3, 95 % CI 1.5-3.7, p < 0.001) and digital ulcers (OR 1.6, 95 % CI 1.0-2.4, p = 0.03) were predictive of PAH. This model had an area under the curve of 0.7 and concordance of 91.8 %. When analysed by disease subtype, the presence of calcinosis (OR 2.2, 95 % CI 1.4 3.7, p = 0.01), sicca symptoms (OR 2.6, 95 % CI 1.5-4.6, p = 0.001), mild ILD (OR 2.3, 95 % CI 1.4-3.8, p = 0.001) and digital ulcers (OR 1.9, 95 % CI 1.2-3.7, p = 0.01) were predictive of PAH in lcSSc; and oesophageal stricture (OR 4.4, 95 % CI 1.9-10.5, p = 0.001), mild ILD (OR 2.8, 95 % CI 1.2-6.8, p = 0.02) and ACA (OR 5.2, 95 % CI 1.8-14.8, p = 0.002) were predictive of PAH in dcSSc. CONCLUSIONS: The incidence and prevalence of PAH in this cohort are 0.7 % per annum and 8.4 %, respectively. The clinical-serologic risk factors for PAH differ based on disease subtype. In both subtypes, mild ILD is associated with PAH, suggesting the possibility of common pathogenic mechanisms underlying both of these disease manifestations. This model identifies a subset of patients at an appreciably higher risk of developing PAH, who should be screened and would in future, benefit from preventative therapies. PMID- 27677582 TI - Erratum to: Oncolytic virus efficiency inhibited growth of tumour cells with multiple drug resistant phenotype in vivo and in vitro. PMID- 27677580 TI - Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene. AB - Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2.15 * 10-09), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 * 10-06), and further show it is an eQTL for FNDC1 (P=9.3 * 10-05). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM. PMID- 27677583 TI - Index for Volume 226. PMID- 27677581 TI - Rapid high-throughput cloning and stable expression of antibodies in HEK293 cells. AB - Single-cell based amplification of immunoglobulin variable regions is a rapid and powerful technique for cloning antigen-specific monoclonal antibodies (mAbs) for purposes ranging from general laboratory reagents to therapeutic drugs. From the initial screening process involving small quantities of hundreds or thousands of mAbs through in vitro characterization and subsequent in vivo experiments requiring large quantities of only a few, having a robust system for generating mAbs from cloning through stable cell line generation is essential. A protocol was developed to decrease the time, cost, and effort required by traditional cloning and expression methods by eliminating bottlenecks in these processes. Removing the clonal selection steps from the cloning process using a highly efficient ligation-independent protocol and from the stable cell line process by utilizing bicistronic plasmids to generate stable semi-clonal cell pools facilitated an increased throughput of the entire process from plasmid assembly through transient transfections and selection of stable semi-clonal cell pools. Furthermore, the time required by a single individual to clone, express, and select stable cell pools in a high-throughput format was reduced from 4 to 6months to only 4 to 6weeks. PMID- 27677585 TI - Bleeding complications of anticoagulant therapy in sepsis-induced disseminated intravascular coagulation. PMID- 27677584 TI - Nitric oxide levels in patients with diabetes mellitus: A systematic review and meta-analysis. AB - BACKGROUND: Altered serum nitric oxide (NO) levels in patients with diabetes mellitus (DM) have been reported by different studies; however, results are still controversial. Until this date, no meta-analysis evaluated the association of NO levels with DM. Thus, this paper describes a meta-analysis conducted to evaluate if there is a relationship between NO levels and type 1 DM (T1DM) or type 2 DM (T2DM). METHODS: A literature search was done to identify all studies that investigated NO levels between T1DM or T2DM patients (cases) and non-diabetic subjects (controls). Measurement of nitrate and nitrite (NOx - the stable NO products) were used to estimate NO concentrations because they closely reflect NO bioavailability. Weighted mean differences (WMD) of NOx levels between case and control samples were calculated for T1DM and T2DM groups. RESULTS: Thirty studies were eligible for inclusion in the meta-analysis (8 in T1DM samples and 22 in T2DM samples). NOx levels were increased in European T1DM patients compared with controls [random effect model (REM) WMD = 8.55, 95% CI 2.88 - 14.21]. No other ethnicity was evaluated in T1DM studies. NOx levels were also increased in both European (REM WMD = 18.76, 95% CI 1.67 - 35.85) and Asian (REM WMD = 18.41, 95% CI 8.01 - 28.81) T2DM patients, but not in Latin American patients compared with controls. CONCLUSIONS: This meta-analysis detected a significant increase in NOx levels in European T1DM patients as well as European and Asian T2DM patients. Further studies in other ethnicities are necessary to confirm these data. PMID- 27677586 TI - Differential network analysis from cross-platform gene expression data. AB - Understanding how the structure of gene dependency network changes between two patient-specific groups is an important task for genomic research. Although many computational approaches have been proposed to undertake this task, most of them estimate correlation networks from group-specific gene expression data independently without considering the common structure shared between different groups. In addition, with the development of high-throughput technologies, we can collect gene expression profiles of same patients from multiple platforms. Therefore, inferring differential networks by considering cross-platform gene expression profiles will improve the reliability of network inference. We introduce a two dimensional joint graphical lasso (TDJGL) model to simultaneously estimate group-specific gene dependency networks from gene expression profiles collected from different platforms and infer differential networks. TDJGL can borrow strength across different patient groups and data platforms to improve the accuracy of estimated networks. Simulation studies demonstrate that TDJGL provides more accurate estimates of gene networks and differential networks than previous competing approaches. We apply TDJGL to the PI3K/AKT/mTOR pathway in ovarian tumors to build differential networks associated with platinum resistance. The hub genes of our inferred differential networks are significantly enriched with known platinum resistance-related genes and include potential platinum resistance-related genes. PMID- 27677587 TI - Hsp60 exerts a tumor suppressor function by inducing cell differentiation and inhibiting invasion in hepatocellular carcinoma. AB - Heat shock protein 60 (Hsp60), a typical mitochondrial chaperone, is associated with progression of various cancers. However, its expression and significance in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, the mRNA and protein expression of Hsp60 in HCC tissues were detected by quantitative RT-PCR (n=24), western blot (n=7), and immunohistochemical staining (n=295), respectively. The correlation between Hsp60 expression and clinicopathological characteristics of HCC patient was also analyzed. Meanwhile, the influence of Hsp60 on malignant phenotype of HCC cells was further investigated. We found that expression of Hsp60 was significantly downregulated in HCC tissues compared to peritumor tissues. Hsp60 expression was significantly correlated with serum alpha -foetoprotein (AFP) level and tumor differentiation grade. Moreover, high Hsp60 expression cancer/pericancer (C/P) ratio was associated with a better overall survival rate (P=0.035, n=295). The prognostic implication of Hsp60 in HCC was further confirmed in another cohort of 107 HCC patients (P=0.027). Up-regulation of Hsp60 remarkably induced the cell differentiation and inhibited the invasive potential of HCC in vitro and in vivo. Intriguingly, the down-regulation of Hsp60 significantly impaired mitochondrial biogenesis. Although more data are required to clarify the underling mechanism responsible for function of Hsp60, our results suggested that the effect of Hsp60 on differentiation and invasion of HCC cells might be associated with mitochondrial biogenesis. Collectively, our findings indicated that Hsp60 exerted a tumor suppressor function, and might serve as a potential therapeutic target in the treatment of HCC. PMID- 27677588 TI - CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis. AB - The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as "miRNA sponge". Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out. The overlapped predicted miRNAs as downstream targets of circRNAs and upstream regulators of mRNAs were verified by qRT-PCR and final circRNA-miRNA-mRNA network was constructed. Gene Ontology (GO) and KEGG pathway analysis were further applied to enrich the huge mRNA microarray data. To sum up, there were 69 up and 63 down regulated circRNAs as well as 2760 up and 2465 down regulated mRNAs in NASH group, comparing with control group. Randomly selected 13 of 14 mRNAs and 2 of 8 circRNAs were successfully verified by qRT-PCR. Through predicted overlapped miRNA verification, four circRNA-miRNA-mRNA pathways were constructed, including circRNA_002581-miR-122-Slc1a5, circRNA_002581- miR-122-Plp2, circRNA_002581-miR 122-Cpeb1 and circRNA_007585-miR-326- UCP2. GO and KEGG pathway analysis also enriched specific mRNAs. Therefore, circRNA profile may serve as candidate for NASH diagnosis and circRNA-miRNA -mRNA pathway may provide novel mechanism for NASH. PMID- 27677590 TI - Classifying lower grade glioma cases according to whole genome gene expression. AB - OBJECTIVE: To identify a gene-based signature as a novel prognostic model in lower grade gliomas. RESULTS: A gene signature developed from HOXA7, SLC2A4RG and MN1 could segregate patients into low and high risk score groups with different overall survival (OS), and was validated in TCGA RNA-seq and GSE16011 mRNA array datasets. Receiver operating characteristic (ROC) was performed to show that the three-gene signature was more sensitive and specific than histology, grade, age, IDH1 mutation and 1p/19q co-deletion. Gene Set Enrichment Analysis (GSEA) and GO analysis showed high-risk samples were associated with tumor associated macrophages (TAMs) and highly invasive phenotypes. Moreover, HOXA7-siRNA inhibited migration and invasion in vitro, and downregulated MMP9 at the protein level in U251 glioma cells. METHODS: A cohort of 164 glioma specimens from the Chinese Glioma Genome Atlas (CGGA) array database were assessed as the training group. TCGA RNA-seq and GSE16011 mRNA array datasets were used for validation. Regression analyses and linear risk score assessment were performed for the identification of the three-gene signature comprising HOXA7, SLC2A4RG and MN1. CO NCLUSIONS: We established a three-gene signature for lower grade gliomas, which could independently predict overall survival (OS) of lower grade glioma patients with higher sensitivity and specificity compared with other clinical characteristics. These findings indicate that the three-gene signature is a new prognostic model that could provide improved OS prediction and accurate therapies for lower grade glioma patients. PMID- 27677592 TI - The Collective Direction of Attention Diffusion. AB - We find that the flow of attention on the Web forms a directed, tree-like structure implying the time-sensitive browsing behavior of users. Using the data of a news sharing website, we construct clickstream networks in which nodes are news stories and edges represent the consecutive clicks between two stories. To identify the flow direction of clickstreams, we define the "flow distance" of nodes (Li), which measures the average number of steps a random walker takes to reach the ith node. It is observed that Li is related with the clicks (Ci) to news stories and the age (Ti) of stories. Putting these three variables together help us understand the rise and decay of news stories from a network perspective. We also find that the studied clickstream networks preserve a stable structure over time, leading to the scaling between users and clicks. The universal scaling behavior is confirmed by the 1,000 Web forums. We suggest that the tree-like, stable structure of clickstream networks reveals the time-sensitive preference of users in online browsing. To test our assumption, we discuss three models on individual browsing behavior, and compare the simulation results with empirical data. PMID- 27677589 TI - FGF4 induces epithelial-mesenchymal transition by inducing store-operated calcium entry in lung adenocarcinoma. AB - Several fibroblast growth factor (FGF) isoforms act to stimulate epithelial mesenchymal transition (EMT) during cancer progression. FGF4 and FGF7 are two ligands of FGF receptor 2 (FGFR2). Using two lung adenocarcinoma (ADC) cell lines, A549 and H1299, we showed that FGF4, but not FGF7, altered cell morphology, promoted EMT-associated protein expression, and enhanced cell proliferation, migration/invasion and colony initiation. In addition, FGF4 increased store-operated calcium entry (SOCE) and expression of the calcium signal-associated protein Orai1. The SOCE inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or Orai1 knockdown reversed all of the EMT-promoting effects of FGF4. BHQ also inhibited FGF4-induced EMT in a mouse xenograft model. Finally, 60 human lung ADC samples and 21 sets of matched specimens (primary and metastatic foci in lymph nodes from one patient) were used to confirm the clinicopathologic significance of FGF4 and its correlation with E-cadherin, Vimentin and Orai1 expression. Our study thus shows that FGF4 induces EMT by elevating SOCE in lung ADC. PMID- 27677591 TI - Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka. AB - In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage. PMID- 27677593 TI - Self-assembling peptide hydrogel for intervertebral disc tissue engineering. AB - : Cell-based therapies for regeneration of intervertebral discs are regarded to hold promise for degenerative disc disease treatment, a condition that is strongly linked to lower back pain. A de novo self-assembling peptide hydrogel (SAPH), chosen for its biocompatibility, tailorable properties and nanofibrous architecture, was investigated as a cell carrier and scaffold for nucleus pulposus (NP) tissue engineering. Oscillatory rheology determined that the system would likely be deliverable via minimally invasive procedure and mechanical properties could be optimised to match the stiffness of the native human NP. After three-dimensional culture of NP cells (NPCs) in the SAPH, upregulation of NP-specific genes (KRT8, KRT18, FOXF1) confirmed that the system could restore the NP phenotype following de-differentiation during monolayer culture. Cell viability was high throughout culture whilst, similarly to NPCs in vivo, the viable cell population remained stable. Finally, the SAPH stimulated time dependent increases in aggrecan and type II collagen deposition, two important NP extracellular matrix components. Results supported the hypothesis that the SAPH could be used as a cell delivery system and scaffold for the treatment of degenerative disc disease. STATEMENT OF SIGNIFICANCE: Lower back pain (LBP) prevalence is widespread due to an aging population and the limited efficacy of current treatments. As LBP is strongly associated with intervertebral disc (IVD) degeneration, it is thought that cell-based therapies could alleviate LBP by repairing IVD tissue. Various natural and synthetic biomaterials have been investigated as potential IVD tissue engineering scaffolds. Self-assembling peptide hydrogels (SAPHs) combine advantages of both natural and synthetic biomaterials; for example they are biocompatible and have easily modifiable properties. The present study demonstrated that a de novo SAPH had comparable strength to the native tissue, was injectable, restored the IVD cell phenotype and stimulated deposition of appropriate matrix components. Results illustrated the promise of SAPHs as scaffolds for IVD tissue engineering. PMID- 27677594 TI - Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass. AB - Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-kappaB signaling and an increase in the expression of NF-kappaB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption. PMID- 27677595 TI - Loss of Dnmt3a induces CLL and PTCL with distinct methylomes and transcriptomes in mice. AB - Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EMUSRalpha tTA;Teto-Cre;Dnmt3afl/fl; Rosa26LOXPEGFP/EGFP (Dnmt3aDelta/Delta) mice. The extent to which molecular changes overlap between these diseases is not clear. Using high resolution global methylation and expression analysis we show that whereas patterns of methylation and transcription in normal B-1a cells and CD8 positive T cells are similar, methylomes and transcriptomes in malignant B-1a and CD8+ T cells are remarkably distinct, suggesting a cell-type specific function for Dnmt3a in cellular transformation. Promoter hypomethylation in tumors was 10 times more frequent than hypermethylation, three times more frequent in CLL than PTCL and correlated better with gene expression than hypermethylation. Cross species molecular comparison of mouse and human CLL and PTCL reveals significant overlaps and identifies putative oncogenic drivers of disease. Thus, Dnmt3aDelta/Delta mice can serve as a new mouse model to study CLL and PTCL in relevant physiological settings. PMID- 27677596 TI - Collagen and alpha-Tubulin of Mouse Tympanic Membrane Fibroblasts Treated with Quinolones and Aminoglycosides. AB - Objective To assess collagen and alpha-tubulin levels of mouse tympanic membrane fibroblasts treated with quinolone and aminoglycoside antibiotics at concentrations found in eardrops. Study Design Prospective controlled cell culture study. Setting Academic tertiary medical center. Subjects Mouse tympanic membrane fibroblasts. Methods In experiment 1, fibroblasts were treated with the following for 24 or 48 hours: phosphate-buffered saline (negative control), dilute hydrochloric acid (positive control), 0.5% gatifloxacin, or commercially available 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ofloxacin, 0.5% moxifloxacin, 0.3% gentamicin, or 3.5 mg/mL of neomycin + polymyxin B sulfate + hydrocortisone. In experiment 2, cells were treated with the pure form of gatifloxacin, gentamicin, ofloxacin, or ciprofloxacin. Cells were observed with phase-contrast microscope until harvested. Proteins were extracted for Western blotting with antibodies against collagen alpha1 type I (collagen 1A1) and alpha-tubulin, and for densitometry to quantify levels. Results Collagen and tubulin levels in fibroblasts treated with ofloxacin, moxifloxacin, gatifloxacin, or gentamicin for 24 hours were not different from the saline control. Fibroblasts treated with neomycin + polymyxin B + hydrocortisone, ciprofloxacin + dexamethasone, or ciprofloxacin for 24 hours had lower collagen 1A1 and alpha-tubulin levels (all P < .001) than the negative control. After 48 hours, fibroblasts treated with neomycin + polymyxin B sulfate + hydrocortisone, ciprofloxacin + dexamethasone, ciprofloxacin, or moxifloxacin had lower collagen 1A1 ( P <= .007) and alpha-tubulin ( P < .0001; except ciprofloxacin, P = .033) as compared with control. In experiment 2, only cells treated with ciprofloxacin had lower collagen 1A1 and alpha-tubulin levels and cell viability (all P < .0001) than control. Cytotoxicity assay and phase contrast images mirrored the protein findings. Conclusion The adverse impact of topical antibiotic exposure on tympanic membrane collagen and tubulin protein levels is drug specific. This may be important for selection of ototopical therapy. PMID- 27677597 TI - Why Participate in Peer Review as a Journal Manuscript Reviewer: What's in It for You? AB - The peer review process for scientific journals relies on the efforts of volunteer reviewers. Reviewers are selected due to their expertise in their fields. With so many demands on professional time, the benefits of participating in peer review may not be obvious. However, reviewers benefit by exposure to the latest developments in their fields, facilitating their keeping up-to-date with the latest publications. Tenure committees look favorably on participation in peer review, and invitations to review underscore that the reviewer is a respected subject matter expert. Contacts made during the peer review process can lead to long-lasting collaboration. Continuing medical education credit can be obtained through various mechanisms. Overall, participating in peer review is an important part of career development and should be viewed as a critical component of advancement. PMID- 27677598 TI - Performance Assessment for Mastoidectomy. AB - Objective The aim of this report is to provide a review of the current literature for assessment of performance for mastoidectomy, to identify the current assessment tools available in the literature, and to summarize the evidence for their validity. Data Sources The MEDLINE database was accessed via PubMed. Review Methods Inclusion criteria consisted of English-language published articles that reported use of a mastoidectomy performance assessment tool. Studies ranged from 2007 to November 2015 and were divided into 2 groups: intraoperative assessments and those performed with simulation (cadaveric laboratory or virtual reality). Studies that contained specific reliability analyses were also highlighted. For each publication, validity evidence data were analyzed and interpreted according to conceptual definitions provided in a recent systematic review on the modern framework of validity evidence. Conclusions Twenty-three studies were identified that met our inclusion criteria for review, including 4 intraoperative objective assessment studies, 5 cadaveric studies, 10 virtual reality simulation studies, and 4 that used both cadaveric assessment and virtual reality. Implications for Practice A review of the literature revealed a wide variety of mastoidectomy assessment tools and varying levels of reliability and validity evidence. The assessment tool developed at Johns Hopkins possesses the most validity evidence of those reviewed. However, a number of agreed-on specific metrics could be integrated into a standardized assessment instrument to be used nationally. A universally agreed-on assessment tool will provide a means for developing standardized benchmarks for performing mastoid surgery. PMID- 27677599 TI - Practice Patterns of Sleep Otolaryngologists at Training Institutions in the United States. AB - Objective To assess the practice characteristics of adult sleep otolaryngologists within US otolaryngology residency training programs. Study Design Cross sectional online survey. Setting Otolaryngology residency training programs. Subjects and Methods Program directors from 106 otolaryngology training programs in the United States were contacted. Program directors were instructed to forward a survey to otolaryngologists within the institution who provided Accreditation Council for Graduate Medical Education (ACGME) Otolaryngology Milestone Project feedback in "sleep-disordered breathing." The survey assessed demographics, nonsurgical practices, and surgical/procedural practices of adult sleep otolaryngologists. Data were collected and analyzed. Results Forty-six surveys met inclusion criteria, representing 40 of 106 (38%) programs. Ninety-three percent of respondents reported that residents gained a significant portion of their sleep medicine training from themselves (ie, the respondents), yet only 36% of respondents spent >=50% of their time on sleep medicine/surgery. Forty-one percent reported being board certified in sleep, with 18% having completed an ACGME fellowship in sleep medicine. Respondents with board certification were more likely to spend greater portions of their practice on sleep medicine/surgery, chi2(3, n = 44) = 23.161 ( P < .001), treat non-obstructive sleep apnea sleep disorders (13 of 18 vs 1 of 26, P < .001), interpret polysomnograms (13 of 17 vs 1 of 15, P < .001), and perform drug-induced sleep endoscopy, chi2(1, n = 43) = 5.43, ( P = .02). A similar pattern was seen with stratification by ACGME sleep medicine fellowship. Conclusion This study highlights the variance in practice patterns among sleep otolaryngologists who instruct residents. Board certification and fellowship training in sleep medicine significantly influence breadth of trainee exposure to this field. The highly disparate trainee experiences to sleep otolaryngology across US programs require attention. PMID- 27677600 TI - Effect of Preoperative Counseling on Hospital Length of Stay and Readmissions after Total Laryngectomy. AB - Objective Total laryngectomy (TL) is a high-cost procedure with patients at risk for significant postoperative health care use. Face-to-face preoperative counseling provided by speech-language pathologists is a relatively inexpensive intervention that may improve care quality and decrease costs. We evaluated if preoperative counseling for patients undergoing TL was associated with differences in length of stay (LOS), use of the emergency department (ED), or unplanned readmissions within 30 days of discharge. A secondary analysis identified predictors of these 3 outcomes. Study Design Case series with chart review. Setting Academic medical center in the United States. Subjects and Methods Patients were included if they underwent TL from 2011 to 2015. Patient demographics and comorbidities, surgical characteristics, and perioperative care data were retrieved and analyzed for 116 patients. Univariate and multivariate models were constructed for 3 outcomes. Results LOS was significantly lower for patients receiving counseling (-3.0 days, P = .02). No differences were observed in rates of 30-day ED visits or unplanned readmissions. Care provided by high volume surgeons was associated with decreased LOS ( P = .005), while having postoperative complications increased LOS ( P < .001). High rates of ED visits (12.1%) and readmissions (20.6%) were observed. Discharge to inpatient rehabilitation and the patient's home distance from the institution were predictors of ED visits. TL as salvage therapy and occurrence of postoperative complications were risk factors for readmission. Conclusion Preoperative counseling was associated with marked reduction in LOS following TL without increased readmissions, which suggests that it may promote safe, earlier patient readiness for discharge. PMID- 27677601 TI - Efficacy of Perioperative Lumbar Drainage following Endonasal Endoscopic Cerebrospinal Fluid Leak Repair. AB - Objective Perioperative lumbar drain (LD) use in the setting of endoscopic cerebrospinal fluid (CSF) leak repair is a well-established practice. However, recent data suggest that LDs may not provide significant benefit and may thus confer unnecessary risk. To examine this, we conducted a meta-analysis to investigate the effect of LDs on postoperative CSF leak recurrence following endoscopic repair of CSF rhinorrhea. Data Sources A comprehensive search was performed with the following databases: Ovid MEDLINE (1947 to November 2015), EMBASE (1974 to November 2015), Cochrane Review, and PubMed (1990 to November 2015). Review Method A meta-analysis was performed according to PRISMA guidelines. Results A total of 1314 nonduplicate studies were identified in our search. Twelve articles comprising 508 cases met inclusion criteria. Overall, use of LDs was not associated with significantly lower postoperative CSF leak recurrence rates following endoscopic repair of CSF rhinorrhea (odds ratio: 0.89, 95% confidence interval: 0.40-1.95) as compared with cases performed without LDs. Subgroup analysis of only CSF leaks associated with anterior skull base resections (6 studies, 153 cases) also demonstrated that lumbar drainage did not significantly affect rates of successful repair (odds ratio: 2.67, 95% confidence interval: 0.64-11.10). Conclusions There is insufficient evidence to support that adjunctive lumbar drainage significantly reduces postoperative CSF leak recurrence in patients undergoing endoscopic CSF leak repair. Subgroup analysis examining only those patients whose CSF leaks were associated with anterior skull base resections demonstrated similar results. More level 1 and 2 studies are needed to further investigate the efficacy of LDs, particularly in the setting of patients at high risk for CSF leak recurrence. PMID- 27677602 TI - Foldable and High Sulfur Loading 3D Carbon Electrode for High-performance Li-S Battery Application. AB - Sulfur is a promising cathode material with a high theoretical capacity of 1672 mAh g-1, however, the practical energy density of Li-S battery is far away from such promising due to its low active material utilization and low sulfur loading. Moreover, the challenges of the low electrical conductivity of sulfur and the high solubility of polysulfide intermediates still hinder its practical application. Here, we report a kind of free-standing and foldable cathodes consisting of 3D activated carbon fiber matrix and sulfur cathode. The 3D activated carbon fiber matrix (ACFC) has continuous conductive framework and sufficient internal space to provide a long-distance and continuous high-speed electron pathway. It also gives a very larger internal space and tortuous cathode region to ACFC accommodate a highly sulfur loading and keeps polysulfide within the cathode. The unique structured 3D foldable sulfur cathode using a foldable ACFC as matrix delivers a reversible capacity of about 979 mAh g-1 at 0.2C, a capacity retention of 98% after 100 cycles, and 0.02% capacity attenuation per cycle. Even at an areal capacity of 6 mAh cm-2, which is 2 times higher than the values of Li-ion battery, it still maintains an excellent rate capability and cycling performance. PMID- 27677603 TI - Amphiphilic star PEG-Camptothecin conjugates for intracellular targeting. AB - Camptothecin (CPT) is a naturally occurring cytotoxic alkaloid having a broad spectrum of antitumor activity. Unfortunately, it has low bioavailability and encapsulation efficiency, limiting its clinical use. We report on our efforts to develop a novel drug delivery prototype composed of a short, star hydrophilic polyethylene glycol (PEG) backbone and hydrophobic CPT (PEG4-CPT). The amphiphilic bio-conjugate self-assembles in water into stable spherical nano particles with a mean diameter of 200nm and CPT substitution percentage of 27%w/w. CPT is released in a sustained release profile without burst effect. In addition, PEG4-CPT nano-particles are able to load a co-drug, water soluble or non-water soluble doxorubicin and release them simultaneously with the free CPT. The biological evaluation of PEG4-CPT against HeLa cells showed improved cellular uptake and enhanced cytotoxicity compared to free CPT. Thus, in this approach CPT acts in two ways: As the hydrophobic segment that enables self-assembly in water and as a potent anticancer agent. This concept of combining hydrophobic drugs and short star polymers shows great potential for efficient delivery of hydrophobic chemotrophic drugs as well as for drugs with inherent stability and pharmacokinetic barriers. PMID- 27677604 TI - To Unveil the Molecular Mechanisms of Qi and Blood through Systems Biology-Based Investigation into Si-Jun-Zi-Tang and Si-Wu-Tang formulae. AB - Traditional Chinese Medicine (TCM) is increasingly getting clinical application worldwide. But its theory like QI-Blood is still abstract. Actually, Qi deficiency and blood deficiency, which were treated by Si-Jun-Zi-Tang (SJZT) and Si-Wu-Tang (SWT) respectively, have characteristic clinical manifestations. Here, we analyzed targets of the ingredients in SJZT and SWT to unveil potential biologic mechanisms between Qi deficiency and blood deficiency through biomedical approaches. First, ingredients in SWT and SJZT were retrieved from TCMID database. The genes targeted by these ingredients were chosen from STITCH. After enrichment analysis by Gene Ontology (GO) and DAVID, enriched GO terms with p value less than 0.01 were collected and interpreted through DAVID and KEGG. Then a visualized network was constructed with ClueGO. Finally, a total of 243 genes targeted by 195 ingredients of SWT formula and 209 genes targeted by 61 ingredients of SJZT were obtained. Six metabolism pathways and two environmental information processing pathways enriched by targets were correlated with 2 or more herbs in SWT and SJZT formula, respectively. PMID- 27677605 TI - Population Dietary Salt Reduction and the Risk of Cardiovascular Disease: A Commentary on Recent Evidence. PMID- 27677606 TI - Stroke, Inflammation and the Immune Response: Dawn of a New Era. PMID- 27677609 TI - Erratum to: Removal of pigments from molasses wastewater by combining micro electrolysis with biological treatment method. PMID- 27677608 TI - A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor Reactive B Cells. AB - Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG. PMID- 27677610 TI - Affectivity and narrativity in depression: a phenomenological study. AB - In this study I explore from a phenomenological perspective the relationship between affectivity and narrative self-understanding in depression. Phenomenological accounts often conceive of the disorder as involving disturbances of the narrative self and suggest that these disturbances are related to the alterations of emotions and moods typical of the illness. In this paper I expand these accounts by advancing two sets of claims. In the first place, I suggest that, due to the loss of feeling characteristic of the illness, the narratives with which the patients identified prior to the onset of depression are altered in various ways, thus leading to the weakening or abandonment of the narratives themselves. I then move to show that these autobiographical narratives are replaced by new stories which possess a distinctive structure and I argue that this is dependent upon specific configurations of affective experience, such as existential feelings of guilt, hopelessness, and isolation, and particular forms of temporal and spatial experience. PMID- 27677607 TI - Astrocytes: Integrative Regulators of Neuroinflammation in Stroke and Other Neurological Diseases. AB - Astrocytes regulate neuroinflammatory responses after stroke and in other neurological diseases. Although not all astrocytic responses reduce inflammation, their predominant function is to protect the brain by driving the system back to homeostasis after injury. They receive multidimensional signals within the central nervous system and between the brain and the systemic circulation. Processing this information allows astrocytes to regulate synapse formation and maintenance, cerebral blood flow, and blood-brain barrier integrity. Similarly, in response to stroke and other central nervous system disorders, astrocytes detect and integrate signals of neuronal damage and inflammation to regulate the neuroinflammatory response. Two direct regulatory mechanisms in the astrocyte arsenal are the ability to form both physical and molecular barriers that seal the injury site and localize the neuroinflammatory response. Astrocytes also indirectly regulate the inflammatory response by affecting neuronal health during the acute injury and axonal regrowth. This ability to regulate the location and degree of neuroinflammation after injury, combined with the long time course of neuroinflammation, makes astrocytic signaling pathways promising targets for therapies. PMID- 27677611 TI - Phylogenetic study-based hemagglutinin (HA) gene of highly pathogenic avian influenza virus (H5N1) detected from backyard chickens in Iran, 2015. AB - Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype have been diversified into multiple phylogenetic clades over the past decade and are highly genetically variable. In June 2015, one outbreak of HPAI H5N1 in backyard chickens was reported in the Nogardan village of the Mazandaran Province. Tracheal tissues were taken from the dead domestic chickens (n = 10) and processed for RT-PCR. The positive samples (n = 10) were characterized as HPAI H5N1 by sequencing analysis for the hemagglutinin and neuraminidase genes. Phylogenetic analysis of the samples revealed that the viruses belonged to clade 2.3.2.1c, and cluster with the HPAI H5N1 viruses isolated from different avian species in Bulgaria, Romania, and Nigeria in 2015. They were not closely related to other H5N1 isolates detected in previous years in Iran. Our study provides new insights into the evolution and genesis of H5N1 influenza in Iran and has important implications for targeting surveillance efforts to rapidly identify the spread of the virus into and within Iran. PMID- 27677612 TI - Women with epilepsy initiating a progestin IUD: A prospective pilot study of safety and acceptability. AB - OBJECTIVE: Effective contraception enables women with epilepsy (WWE) to plan their pregnancies and improve outcomes for themselves and their children. Although popular among all women, complex drug interactions limit the efficacy and safety of oral contraceptives (OCs) for WWE. We sought to explore the safety, acceptability, and pharmacokinetic impact of a progestin-containing intrauterine device (IUD) in WWE. METHODS: We enrolled 20 women with well-controlled epilepsy and a stable antiepileptic drug (AED) regimen and who were initiating a progestin containing IUD (levonorgestrel 52 mg) in a prospective, observational study. For each AED, we compared the trough concentration before IUD insertion to the trough concentration 3 weeks, and 3 and 6 months later. Participants recorded seizures in a daily paper diary. We compared seizures that occurred during the month before IUD insertion to those occurring in the 6 months thereafter. Participants completed an acceptability questionnaire at 3 and 6 months. RESULTS: Participants' average age was 28 years; 60% were nulligravid. They reported a history of multiple seizure types. During the baseline month, 75% were seizure free and the remainder reported between one and three seizures. Fourteen received monotherapy and six received polytherapy. Lamotrigine use was most common (n = 12). AED trough concentrations remained stable during the 6 months after IUD insertion, without clinically meaningful deviations from baseline. Diary data showed that seizure frequency worsened in 3, and remained unchanged in 13 and improved in 4 after IUD insertion. Subjectively, no participant believed the IUD worsened her seizure control. All participants were either somewhat or very satisfied with the IUD throughout the study. All participants continued the IUD use at 6 months. No pregnancies occurred. SIGNIFICANCE: This pilot study suggests that the progestin-containing IUD is a safe and acceptable long-acting contraceptive for WWE. PMID- 27677613 TI - Routine evaluation of left ventricular function using CZT-SPECT, with low injected activities and limited recording times. AB - PURPOSE: Gamma-cameras, with Cadmium-Zinc-Telluride (CZT) detectors, allow to perform myocardial perfusion imaging (MPI) with limited injected activities and recorded times. This study aimed at determining whether the routine assessment of left ventricular (LV) function with such limited counts protocols compares well with reference values from cardiac MRI. METHODS: The study included patients who have undergone cardiac MRI and an MPI routinely planned on a CZT camera with a low-dose protocol (120 MBq of Sestamibi for stress and 360 MBq at rest for 75 kg body weight), while targeting the recording of only 500 myocardial kcounts in order to limit the recording times (<10 minutes for stress, <4 minutes for rest). SPECT images were reconstructed with a method maintaining rather high spatial (8 mm) and temporal (16 frames/cycle) resolutions. RESULTS: Seventy-six patients were included, and mean effective dose was 3.5 +/- 1.7 mSv for the total MPI protocol. Correlations between CZT-SPECT and MRI were good to excellent for ejection fraction (r 2 = 0.77), end-diastolic (r 2 = 0.88) and end-systolic (r 2 = 0.93) volumes, and the analysis of segmental contractility correlated well between the two techniques (kappa score = 0.72 +/- 0.02). CONCLUSION: LV function, assessed on a CZT camera with low injected activities and limited recording times, correlates well with the reference assessment from cardiac MRI. PMID- 27677614 TI - Granuloma after sling surgery: an attempt to answer the 'why' and 'what to do next'. AB - PURPOSE: To review cases of granuloma formation after sling surgery with a view to find out possible aetiological factors and propose a further plan of management MATERIALS AND METHODS: A retrospective analysis of 120 eyes of 108 patients who underwent frontalis sling surgery with silicone rod from Jan 2008 to Dec 2015 was conducted. All patients with severe ptosis and poor levator function who underwent frontalis sling surgery with silicone rod were included in the study irrespective of the cause of ptosis and method of passing the sling. A complete ophthalmic and ptosis examination was done. In all the cases, the prolene suture was tied over the sleeve to tighten it and it was buried along with the silicone rod in forehead pocket. All the cases with granuloma formation were first subjected to a microbiological examination including culture and sensitivity to antibiotics. All the patients were given a trial of antibiotics. RESULTS: We encountered 10 cases of granuloma in 120 eyes of 108 patients operated during this period. The duration between time of surgery and presentation varied from 2 weeks to 4 months. The microbiological examination revealed positive culture in 5 cases. None of the cases responded to the course of antibiotics given for 10 days. The histopathological examination done in 5 cases (2 of them culture positive and 3 of them culture negative) revealed granulomatous inflammation of non-specific type. The sling was explanted in all cases which resulted in prompt resolution of granuloma in 7-10 days. CONCLUSIONS: The granuloma is primarily due to exposure of the sling itself or the sleeve enveloping the sling or the suture tied around the sleeve thereby. They do not respond to antibiotics but respond very well to explantation. These patients can be taken up for re-sling surgery after a waiting period of 3 months. PMID- 27677615 TI - Development of a Low-Cost Ecotoxicological Bioassay Based on the Feeding Behaviour of the Aquatic Snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca). AB - Conventional acute tests are not suited to assess the effects of toxicants, because they do not use the concentrations that are usually found in natural ecosystems. By contrast, nonlethal realistic concentrations may cause deleterious effects on animal fitness as a consequence of behaviour impairment. Behaviour is a good integrative variable of complex biochemical and physiological processes. Therefore, bioassays based on behaviour are a useful tool in ecotoxicology. In this study, two bioassays were conducted: (1) acute bioassay (48 h) of acetone on the aquatic snail Potamopyrgus antipodarum, and (2) video-recording behavioural bioassay with pulse exposures to acetone to assess its effects on feeding behaviour. In the latter, animals were exposed to three pulses of acetone (24 h each) with 6 days of postexposure after each pulse. This design allowed us to assess the degree of feeding behaviour recovery after exposure and the effects of repeated pulses. Our results show that postexposure periods have an important effect on the recovery of normal feeding behaviour and that this developed bioassay is an ecotoxicological tool with a relatively low-cost and a short-time consuming. The application of this new tool to different ecotoxicological requirements is discussed. PMID- 27677616 TI - Accidental hypothermia: factors related to long-term hospitalization. A retrospective study from northern Finland. AB - Accidental hypothermia has a low incidence, but is associated with a high mortality rate. Knowledge about concomitant factors, complications, and length of hospital stay is limited. A retrospective cohort study on patients with accidental hypothermia admitted to Oulu University Hospital in Finland, over a 5 year period. Patients were categorized as short-stay patients (7 days or less) and long-stay patients (more than 7 days) according to their length of stay in hospital. From a total of 105 patients, 67 patients were included in the analyses. Alcohol abuse was the most common concomitant factor (54 %). Median length of hospital stay was 4 days, and 16 patients (24 %) stayed in hospital over 7 days (median 15 days). Thirty-day mortality was low (14/105, 13 %). Patients with long-term hospitalization had a lower initial temperature (28.4 versus 31.2 degrees C, p = 0.011), a lower level of consciousness (GCS score 8.4 versus 12.8, p = 0.003), more severe acidosis (pH 7.08 versus 7.28, p = 0.005, and lactate 7.2 versus 3.9, p = 0.043), and a lower level of platelets (183 versus 242, p = 0.041) on admission compared with short-stay patients. Thirty-six patients (54 %) had at least one complication, and this prolonged median hospital treatment for 2.5 days (p < 0.001). Alcohol is the most common concomitant factor and every fourth patient spends more than 7 days in hospital. Long-term hospitalization is related to a lower core temperature, lower consciousness, more severe lactic acidosis, lower platelet level and infections, rhabdomyolysis, and renal failure. PMID- 27677617 TI - Nutritional quality of packaged foods targeted at children in Brazil: which ones should be eligible to bear nutrient claims? AB - OBJECTIVES: This study aimed to assess the nutritional quality of food products marketed at children, with and without nutrient claims, using two different approaches. METHODS: Analyses were performed based on a data set with food composition and labelling data from every packaged food marketed at children sold in a major Brazilian supermarket (n=535). Foods were classified as 'healthier' and 'less healthy' according to the UK/Ofcom nutrient profile model and to the NOVA classification based on the level of food processing. Pearson's chi2 test was used to compare proportions between models. Agreement was assessed using Cohen's kappa-statistic (P<0.05). RESULTS: The NOVA model was stricter than the UK/Ofcom model, classifying more products as 'less healthy' (91.4%) compared with the nutrient profile-based model (75.0%; P<0.001). Agreement between models was 79.4% (k=0.30), because 72.9% (n=390) of products were categorised as 'less healthy' by both models, and 6.5% (n=35) as 'healthier'. Half of the food products marketed at children from the database (270; 50.5%) bore nutrient claims. From these products with nutrient claims, 95.9% (92.8-98.0) were classified as 'less healthy' by the NOVA model, whereas this percentage was 74.1% (68.4-79.2) according to the UK/Ofcom model (P<0.05). CONCLUSIONS: The high number of foods with low nutritional quality being marketed at children via product packaging and nutrient claims should be of concern to policy makers wanting to improve children's diets and to tackle childhood obesity. The implementation of nutritional quality criteria to ensure that foods targeted at children should be eligible to bear nutrient claims on their labels could avoid a situation where claims mask the overall nutritional status of a food. PMID- 27677618 TI - Associations between self-reported and objectively measured physical activity, sedentary behavior and overweight/obesity in NHANES 2003-2006. AB - OBJECTIVE: To investigate associations between self-reported and objectively measured physical activity, sedentary behavior and overweight/obesity based on percent body fat measured with Dual Energy X-Ray Absorptiometry (DXA), waist circumference (WC), waist-to-height ratio and body mass index, focusing on different intensities and domains of physical activity. METHODS: Data from NHANES 2003-2006 were analyzed using linear and ordered logistic regression analyses. A total of 4794 individuals aged 18-69 years with valid physical activity and DXA data were included. Objectively measured physical activity and sedentary behavior were assessed using accelerometers, self-reported physical activity using the NHANES physical activity questionnaire. Weight, height, WC and DXA measures were assessed in the mobile examination centers. RESULTS: We observed statistically significant associations between objectively measured moderate and vigorous physical activity and all definitions of overweight/obesity. For total physical activity, the odds of being in the higher percent body fat category were 0.56 (95% confidence interval (CI) 0.41, 0.77) for the medium and 0.30 (95% CI 0.22, 0.40) for the highest physical activity tertile compared with the lowest. For light activities, lifestyle activities and sedentary behavior, associations were only observed in the linear models with percent total body fat but not in the ordered logistic regression models. Regarding self-reported physical activity, consistent significant associations with overweight/obesity were only observed for vigorous and for transport activity. CONCLUSIONS: Regarding moderate and vigorous physical activity, more active individuals were less affected by overweight/obesity than less active individuals, emphasizing the public health effect of physical activity in the prevention of overweight/obesity. The fact that associations were more consistent for objectively measured than for self reported physical activity may be due to bias related to self-reporting. Associations between lower intensity activities and overweight/obesity were weak or inexistent. PMID- 27677619 TI - Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers. AB - Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lobe network is different in newborns from normal-weight or obese mothers. Thirty-four full-term healthy infants from uncomplicated pregnancies were included, with 18 born to normal weight and 16 born to obese mothers. Two weeks after delivery, the infants underwent an magnetic resonance imaging (MRI) examination during natural sleep, which included structural imaging and resting-state functional MRI (fMRI) scans. Independent component analysis was used to identify the prefrontal lobe network, and dual regression was used to compare functional connectivity between groups. Infants born to normal-weight mothers had higher recruiting (P<0.05, corrected) of dorsal anterior cingulate cortex regions to the prefrontal network after adjusting for maternal intelligence quotient, gestational weight gain and infant postmenstrual age, gender, birth weight/length, head circumference and neonatal diet. The functional connectivity strength in dorsal anterior cingulate cortex negatively correlated (P<0.05) with maternal fat mass percentage measured at early pregnancy. This preliminary study indicates that exposure to maternal obesity in utero may be associated with changes in resting-state functional connectivity in the newborn offspring's brain. PMID- 27677620 TI - Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity. AB - OBJECTIVE: Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues. DESIGN: Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks. The CD-fed rats were treated with either grape-seed PAC extract (GSPE) at 25 mg per kg of body weight per day (CD+GSPE group, n=7) or with the vehicle (CD group, n=7) for the last 21 days of the study period. Specific markers for intracellular leptin signalling, inflammation and endoplasmic reticulum stress in the hypothalamus, liver, mesenteric white adipose tissue and skeletal muscle were analysed using immunoblotting and quantitative PCR. RESULTS: GSPE treatment significantly reduced the food intake but did not reverse the hyperleptinemia and body wt gain assessed. However, the animals treated with GSPE exhibited greater hypothalamic activation of signal transducer and activator of transcription-3, which was associated with a rise in the Pomc mRNA levels compared with the CD group. In addition, this restoration of leptin responsiveness was accompanied by lower local inflammation and increased Sirt1 gene expression. The effects of the GSPE treatment in the peripheral tissues were not as evident as those in the hypothalamus, although the GSPE treatment significantly restored the mRNA levels of Socs3 and Ptp1b in the skeletal muscle. CONCLUSIONS: The use of GSPE reduces hyperphagia and improves the central and peripheral leptin resistance associated with diet-induced obesity. Our results suggest that GSPE could exert these effects partially by increasing Sirt1 expression and preventing hypothalamic inflammation. PMID- 27677621 TI - Trajectories of total and central adiposity throughout adolescence and cardiometabolic factors in early adulthood. AB - BACKGROUND/OBJECTIVES: Our aim was to identify trajectories of total and central adiposity from 13 to 21 years, and to investigate how adiposity changes at different phases of adolescence relate to adulthood cardiovascular risk factors. SUBJECTS/METHODS: This study included participants from a population-based cohort (EPITeen), Portugal. Body mass index (BMI) and waist circumference (WC) were measured at 13, 17 and 21 years, and sex- and age-specific z-scores were calculated. Adiposity trajectories were identified using mixture growth models (BMI, n=2901; WC, n=2898). Cardiovascular risk factors were evaluated at 21 years (n=1763): systolic (SBP) and diastolic blood pressure (DBP), insulin resistance (HOMA-IR), triglycerides and cholesterol. Association of trajectory, and changes in adiposity z-scores with each cardiovascular risk factor was estimated by linear regression models. RESULTS: 'Normal', 'high, declining' and 'high, increasing' trajectories were identified in both sexes. 'High, increasing' BMI trajectory was associated with less favorable cardiovascular risk profile at 21 years in both sexes, whereas 'high, declining' presented a more favorable profile, similar to 'normal' trajectory in females. In addition, BMI increases between 13-17 years and 17-21 years were associated with increases in systolic and diastolic blood pressure, and insulin resistance, but more strongly for the later period. For every standard deviation (s.d.) increase in BMI between 17-21 years, mean SBP increased by 1.99 mmHg (95% confidence interval (CI): 1.01; 2.97) for females and 3.83 mmHg (2.67; 4.98) for males; the respective increase was 1.56 mmHg (0.72; 2.40) and 2.80 mmHg (1.97; 3.64) for DBP and 0.27 (0.21; 0.32) and 0.30 (0.24; 0.36) for HOMA-IR (log-transformed). Similar results were found for WC. CONCLUSIONS: Increases in adiposity, particularly from late adolescence to-young adulthood, were associated with unfavorable cardiovascular profile in early adulthood. A benefit on the cardiovascular risk profile for participants in the declining adiposity trajectory was observed. PMID- 27677624 TI - Erratum to: Phase I and pharmacokinetic evaluation of the anti-telomerase agent KML-001 with cisplatin in advanced solid tumors. PMID- 27677622 TI - Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions. AB - BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-beta1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-beta1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs. PMID- 27677623 TI - Application of bee venom and its main constituent melittin for cancer treatment. AB - Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles. In this review, we summarize the current knowledge regarding anticancer effects of bee venom and its main compound MEL on different kinds of tumor cells as well as elucidate their possible anticancer mechanisms. It could be concluded that MEL exerts multiple effects on cellular functions of cancerous cells such as proliferation, apoptosis, metastasis, angiogenesis as well as cell cycle, and the anticancer processes involve diverse signal molecules and regulatory pathways. We also highlight the recent research progress for efficient delivery of MEL peptide, thus providing new ideas and hopeful strategies for the in vivo application of MEL. PMID- 27677625 TI - The C'JAAD: a French team for early intervention in psychosis in Paris. AB - AIM: The aim is to describe a centre operating in Paris that pioneers the early intervention for young people at the onset and at high risk of psychosis in France. METHODS: Comprehensive descriptive analysis of different clinical and service measures is used in describing the implementation of the C'JAAD (Evaluation Centre for Young Adults and Adolescents) using data from an ongoing prospective non-interventional research programme. RESULTS: Over a 2-year period, 151 patients were referred to the C'JAAD and included in the ICAAR research programme. After evaluation by the Comprehensive Assessment of the At-Risk Mental States Scale, 53.7% were identified at risk of developing a psychosis, 20.6% presented a full-blown psychosis and 25.7% were considered not at risk of developing a psychosis. A total of 84% of the at-risk subjects suffered from a psychiatric co-morbidity, of which anxiodepressive symptoms being the most frequent (39%). The global functioning of these at-risk subjects was seriously impaired (average Social and Occupational Functioning Assessment Scale score = 48.9). More than one third of the patients was self-referred (33.8%), 22.5% were addressed by a psychiatrist whereas 10.6% were referred by a general practitioner. CONCLUSIONS: In this paper, we report for the first time the activities of the C'JAAD, the pioneer unit in France for early detection and treatment of young adults with early psychosis. These observations indicate that such early intervention centre is a feasible and sustainable extension of traditional care for people with mental disorders in this country and offers promising perspective for the development of further centres. PMID- 27677626 TI - First Experiences with the New Enterprise2(r) Stent. AB - INTRODUCTION: Stent-assisted coiling of wide-necked intracranial aneurysms has become an established treatment and has significantly benefited from the introduction of compliant, self-expanding devices, such as the Enterprise VRD (EP VRD). We report our experiences with the successor model, the Enterprise2 (EP2) stent in stent-assisted coiling as well as in the treatment of atherosclerotic stenosis. MATERIALS AND METHODS: In 11 consecutive patients 12 EP2 were used to treat 9 intracranial aneurysms and 2 stenoses. RESULTS: All stents could easily be delivered including partial or complete recapturing when necessary. In two cases with sharp angled curves in the carotid siphon there was kinking and flattening of the stent resulting in incomplete wall apposition of the stent. Moreover, when vascular anatomy showed curves with angles >50 degrees it was regularly observed that the proximal stent markers were asymmetrically arranged along the vessel circumference without influence on the stent apposition. Both findings could be reproduced in a silicone flow model. CONCLUSION: The EP2 performed well in our small patient cohort; however, above a critical acute angle there may be incomplete wall apposition of the stent. PMID- 27677627 TI - Spontaneous and Unruptured Chronic Intracranial Artery Dissection : High resolution Magnetic Resonance Imaging Findings. AB - PURPOSE: The aim of this article is to present high-resolution magnetic resonance imaging (HR-MRI) findings of chronic stage spontaneous and unruptured intracranial artery dissection (ICAD). MATERIAL AND METHODS: From March 2012 to April 2016 a total of 29 patients (15 male and14 female, age range 37-68 years) with chronic stage spontaneous and unruptured ICAD (vertebral artery 27, posterior inferior cerebellar artery 1 and middle cerebral artery 1) were retrospectively enrolled. Patients underwent HR-MRI more than 2 months (median interval 564 days, range 69-391 days) after symptom onset and were diagnosed at symptom onset or at the first imaging acquisition, which included luminal angiography and/or HR-MRI with clinical information. The HR-MRI findings were evaluated against those of luminal angiography on the basis of the lumen wall morphology, including thickening, contrast enhancement and residual dissection. RESULTS: The HR-MRI findings were classified into complete normalization (normal lumen and wall with or without mild enhancement, n = 6), complete normalization with minimal wall changes (focal wall thickening with enhancement but normal luminal angiography, n = 8), incomplete normalization (focal wall thickening with enhancement with dilatation and stenosis on luminal angiography, n = 4), dissecting aneurysm (fusiform aneurysm with residual dissection findings, n = 8) and occlusion (small outer arterial diameter with diffuse contrast enhancement, n = 3). CONCLUSION: The use of HR-MRI can demonstrate the distinguishing morphological features of chronic stage of spontaneous and unruptured ICAD as complete normalization, complete normalization with minimal wall changes, incomplete normalization, dissecting aneurysm and occlusion. PMID- 27677629 TI - Setting population targets for mammals using body mass as a predictor of population persistence. AB - Conservation planning and biodiversity assessments need quantitative targets to optimize planning options and assess the adequacy of current species protection. However, targets aiming at persistence require population-specific data, which limit their use in favor of fixed and nonspecific targets, likely leading to unequal distribution of conservation efforts among species. We devised a method to derive equitable population targets; that is, quantitative targets of population size that ensure equal probabilities of persistence across a set of species and that can be easily inferred from species-specific traits. In our method, we used models of population dynamics across a range of life-history traits related to species' body mass to estimate minimum viable population targets. We applied our method to a range of body masses of mammals, from 2 g to 3825 kg. The minimum viable population targets decreased asymptotically with increasing body mass and were on the same order of magnitude as minimum viable population estimates from species- and context-specific studies. Our approach provides a compromise between pragmatic, nonspecific population targets and detailed context-specific estimates of population viability for which only limited data are available. It enables a first estimation of species-specific population targets based on a readily available trait and thus allows setting equitable targets for population persistence in large-scale and multispecies conservation assessments and planning. PMID- 27677628 TI - Aspirin use and the incidence of breast, colon, ovarian, and pancreatic cancers in elderly women in the Iowa Women's Health Study. AB - PURPOSE: Few studies have evaluated the chemopreventive effect of aspirin on the cancer risk in elderly women. We examined associations between frequency, dose, and duration of aspirin use with incidence of 719 aspirin-sensitive cancers (cancers of colon, pancreas, breast, and ovaries) in the Iowa Women's Health Study (IWHS), a prospective cohort of women over 70 years old. METHODS: Aspirin frequency, dose, and duration were self-reported in the 2004 IWHS questionnaire. Women were followed-up to 2011. Cancer cases were ascertained by linkage to the Iowa State Health Registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CI). RESULTS: Among the 14,386 women, 30 % were nonusers of aspirin; 34 % used low-dose aspirin, and 36 % used regular- or high-dose aspirin. Compared with nonuse of aspirin, the HRs (95 % CI) for incidence of aspirin-sensitive cancers were 0.87 (0.72-1.06) for regular to high doses of aspirin use, 0.95 (0.80-1.13) for aspirin use 6+ times per week, and 0.93 (0.74-1.17) for aspirin use for 10+ years. For cumulative aspirin use, HR (95 % CI) was 0.87 (0.70-1.09) for >60,000 mg of aspirin per year and 0.95 (0.75-1.21) for >280,000 mg of aspirin in their lifetime, versus nonuse of aspirin. Results were similar for the all-cause cancer death as an endpoint, with a significant inverse association observed between lifetime aspirin dose and cancer mortality [<95,000 mg vs nonuser HR 0.76 (0.61-0.95)]. CONCLUSIONS: These findings suggest that aspirin use may prevent incident breast, colon, pancreatic, and ovarian cancer in elderly women. PMID- 27677630 TI - Discovery and introgression of the wild sunflower-derived novel downy mildew resistance gene Pl 19 in confection sunflower (Helianthus annuus L.). AB - KEY MESSAGE: A new downy mildew resistance gene, Pl 19 , was identified from wild Helianthus annuus accession PI 435414, introduced to confection sunflower, and genetically mapped to linkage group 4 of the sunflower genome. Wild Helianthus annuus accession PI 435414 exhibited resistance to downy mildew, which is one of the most destructive diseases to sunflower production globally. Evaluation of the 140 BC1F2:3 families derived from the cross of CMS CONFSCLB1 and PI 435414 against Plasmopara halstedii race 734 revealed that a single dominant gene controls downy mildew resistance in the population. Bulked segregant analysis conducted in the BC1F2 population with 860 simple sequence repeat (SSR) markers indicated that the resistance derived from wild H. annuus was associated with SSR markers located on linkage group (LG) 4 of the sunflower genome. To map and tag this resistance locus, designated Pl 19 , 140 BC1F2 individuals were used to construct a linkage map of the gene region. Two SSR markers, ORS963 and HT298, were linked to Pl 19 within a distance of 4.7 cM. After screening 27 additional single nucleotide polymorphism (SNP) markers previously mapped to this region, two flanking SNP markers, NSA_003564 and NSA_006089, were identified as surrounding the Pl 19 gene at a distance of 0.6 cM from each side. Genetic analysis indicated that Pl 19 is different from Pl 17 , which had previously been mapped to LG4, but is closely linked to Pl 17 . This new gene is highly effective against the most predominant and virulent races of P. halstedii currently identified in North America and is the first downy mildew resistance gene that has been transferred to confection sunflower. The selected resistant germplasm derived from homozygous BC2F3 progeny provides a novel gene for use in confection sunflower breeding programs. PMID- 27677631 TI - Fine mapping and candidate gene analysis of qHD5, a novel major QTL with pleiotropism for yield-related traits in rice (Oryza sativa L.). AB - KEY MESSAGE: A major QTL for heading date, qHD5, was fine-mapped to a 52.59-kb region on the short arm of rice chromosome 5. Heading date (HD) is one of the most important traits that enables rice to adapt to seasonal differences and specific growth conditions in diverse growing regions. In this study, a major effect quantitative trait locus (QTL), qHD5, was resolved as a single Medelian factor that causes NIL(BG1) and NIL(XLJ) (two near-isogenic lines (NILs) used in our study) to have at a minimum of 10-day difference in HD under both long-day and short-day conditions in rice. qHD5 was initially mapped to a 309.52-kb genomic region in our previous study. Here, using an advanced BC4F3 population and map-based cloning, we further narrowed the location of qHD5 to a 52.59-kb region between the H71 and RD502 markers. Sequence analysis revealed that Os05g03040, which putatively encodes an AP2 (APETALA2) transcription factor, has six single nucleotide polymorphisms (SNPs) between NIL(BG1) and NIL(XLJ). On this basis, this gene was concluded to be the most probable candidate gene for qHD5. Our results also showed that Hd3a, RFT1, Hd1, Ehd1, and Ghd7 were differentially expressed in the two NILs. Moreover, qHD5 was found to affect yield-related traits such as flag leaf width, flag leaf length, branch number, and 1000-grain weight. PMID- 27677632 TI - Sudden infant death syndrome: exposure to cigarette smoke leads to hypomethylation upstream of the growth factor independent 1 (GFI1) gene promoter. AB - PURPOSE: Smoking during pregnancy has long been known as an important risk factor for sudden infant death syndrome (SIDS). However, the precise relationship between the smoking behavior of the mother and SIDS still remains unclear. In this study, the influence of prenatal smoking exposure on the childrens' DNA methylation state of a CpG island located upstream of the promoter of the growth factor independent 1 (GFI1) gene was analyzed. METHODS: Blood samples of well defined SIDS cases with non-smoking mothers (n = 11), SIDS cases with smoking mothers during pregnancy (n = 11), and non-SIDS cases (n = 6) were obtained from a previous study and methylation states were determined by bisulfite sequencing. RESULTS: Significant hypomethylation was observed in this CpG island in SIDS cases with cigarette smoke exposure compared to non-exposed cases. The strongest effect in this CpG island was observed for 49 CpG sites located within a transcription factor binding site. Coding for a transcriptional repressor, GFI1 plays an important role in various developmental processes. Alterations in the GFI1 expression might be linked to various conditions that are known to be associated with SIDS, such as dysregulated hematopoiesis and excessive inflammatory response. CONCLUSION: Data obtained in this study show that analysis of methylation states in cases of sudden infant death syndrome might provide a further important piece of knowledge toward understanding SIDS, and should be investigated in further studies. PMID- 27677633 TI - Forensic postmortem computed tomography: volumetric measurement of the heart and liver. AB - PURPOSE: The purpose of this study was to investigate the utility of postmortem computed tomography (PMCT) images in estimating organ sizes and to examine the use of the cardiothoracic ratio (CTR). METHODS: We included 45 individuals (19 females), who underwent a medico-legal autopsy. Using the computer software program Mimics(r), we determined in situ heart and liver volumes derived from linear measurements (width, height and depth) on a whole body PMCT-scan, and compared the volumes with ex vivo volumes derived by CT-scan of the eviscerated heart and liver. The ex vivo volumes were also compared with the organ weights. Further, we compared the CTR with the ex vivo heart volume and a heart weight ratio (HWR). Intra- and inter-observer analyses were performed. RESULTS: We found no correlation between the in situ and ex vivo volumes of the heart and liver. However, a highly significant correlation was found between the ex vivo volumes and weights of the heart and liver. No correlations between CTR and the ex vivo heart volume nor with HWR was found. Concerning cardiomegaly, we found no agreement between the CTR and HWR. The intra- and inter-observer analyses showed no significant differences. CONCLUSIONS: Noninvasive in situ PMCT methods for organ measuring, as performed in this study, are not useful tools in forensic pathology. The best method to estimate organ volume is a CT-scan of the eviscerated organ. PMCT-determined CTR seems to be useless for ascertaining cardiomegaly, as it neither correlated with the ex vivo heart volume nor with the HWR. PMID- 27677634 TI - Selective and effective targeting of chronic myeloid leukemia stem cells by topoisomerase II inhibitor etoposide in combination with imatinib mesylate in vitro. AB - Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (TKIs) have improved chronic myeloid leukemia (CML) patient survival markedly but fail to eradicate quiescent CML leukemia stem cells (LSCs). Thus, strategies targeting LSCs are required to induce long-term remission and achieve cure. Here, we investigated the ability of topoisomerase II (Top II) inhibitor etoposide (Eto) to target CML LSCs. Treatment with Eto combined with IM markedly induced apoptosis in primitive CML CD34+ CD38- stem cells resistant to eradication by IM alone, but not in normal hematopoietic stem cells, CML and normal mature CD34- cells, and other leukemia and lymphoma cell lines. The interaction of IM and Eto significantly inhibited phosphorylation of PDK1, AKT, GSK3, S6, and ERK proteins; increased the expression of pro-apoptotic gene Bax; and decreased the expression of anti-apoptotic gene c-Myc in CML CD34+ cells. Top II inhibitors treatment represents an attractive approach for targeting LSCs in CML patients undergoing TKIs monotherapy. PMID- 27677635 TI - Dietitians' perceptions and experience of blenderised feeds for paediatric tube feeding. AB - OBJECTIVE: There is an emerging interest in the use of blenderised food for tube feeding (BFTF). This survey explored paediatric dietitians' perceptions and experiences of BFTF use. DESIGN: A web-based questionnaire was distributed to the Paediatric group of the British Dietetic Association. The survey captured dietitians' personal opinions and experience supporting children on BFTF, and the perceptions of carers. RESULTS: Of the 77 respondents, 19 were aware of professional guidelines and 63 had never received training on BFTF. Thirty-four would not recommend BFTF and 11 would advise against its use; yet 43 would recommend it to supplement commercial feeds. Fifty-seven would change their perception about BFTF if there were evidence-based guidelines. Forty-four would feel confident to support a patient using BFTF. Forty-three had previous experience supporting a patient with BFTF. The main concerns perceived by dietitians, pertinent to the use of BFTF, were nutritional inadequacy (n=71), tube blockages (n=64) and increased infection risk (n=59) but these were significantly higher than those experienced by themselves in clinical practice (p<0.001 for all three). A reduction in reflux and vomiting and increased carer involvement were the main perceived and observed benefits by both dietitians and carers. CONCLUSIONS: The use of these feeds for tube-fed children is increasingly being seen as a viable choice. Dietitians experienced significantly fewer issues with the use of BFTF in clinical practice compared with their self-reported apprehensions in the survey. Well-controlled studies are now needed to objectively assess the benefits, risks, costs and practicality of BFTF. PMID- 27677636 TI - Cancer Drugs Fund requires further reform. PMID- 27677638 TI - Discovery and Biophysical Evaluation of First Low Nanomolar Hits Targeting CYP125 of M. tuberculosis. AB - Tuberculosis, which is predominantly caused by Mycobacterium tuberculosis (Mtb), is still the most lethal bacterial infection with 1.5 million casualties in 2014. Moreover, the fact that the appearance of resistant mutants and long-term treatment are coupled with economic problems in developing countries hampers an efficient therapy. Interference with the essential cholesterol metabolism of Mtb could be a promising novel strategy to fight Mtb infections. CYP125, a P450 enzyme in Mtb, has been shown to play an important role in this metabolic pathway. For this reason, we used a combined screening approach involving surface plasmon resonance spectroscopy and a heme coordination assay to identify new CYP125 binders by employing a focused P450-inhibitor library. We identified the first hits with high affinity and favorable ligand efficiencies. Furthermore, frontrunner compounds also showed selectivity toward CYP121 specific to Mtb and required for its survival. To date, these are the first compounds targeting CYP125 with low nanomolar affinity. PMID- 27677637 TI - The Risk of Achilles or Biceps Tendon Rupture in New Statin Users: A Propensity Score-Matched Sequential Cohort Study. AB - INTRODUCTION: Case reports and pharmacovigilance data reported cases of tendon ruptures in statin users, but evidence from observational studies is scarce and inconclusive. We aimed to assess the association between new statin use and tendon rupture. METHODS: We performed a propensity score (PS)-matched sequential cohort study, using data from the Clinical Practice Research Datalink. Patients aged >=45 years with at least one new statin prescription between 1995 and 2014 were PS-matched within 2-year entry blocks to patients without a statin prescription during the block. We followed patients until they had a recorded Achilles or biceps tendon rupture, completed 5 years of follow-up, or were censored for change in exposure status or another censoring criterion. We calculated hazard ratios (HRs) with 95 % confidence intervals (CIs), applying Cox proportional hazard analyses in the overall cohort (crude and multivariable) and in the PS-matched cohort. We performed subgroup analyses by sex, age, treatment duration, and statin dose. RESULTS: We observed a crude HR of 1.32 (95 % CI 1.21 1.44) in the overall cohort, which attenuated after multivariable adjustment (HR 1.02, 95 % CI 0.92-1.12) and after PS-matching (HR 0.95, 95 % CI 0.84-1.08). Crude HRs were higher in women than in men, but remained around null in both sexes after multivariable adjustment and PS-matching. Subgroup analyses by age, treatment duration, and statin dose revealed null results across all subgroups. CONCLUSION: The results of this cohort study suggest that statin use does not increase the risk of tendon rupture, irrespective of gender, age, statin dose, or treatment duration. PMID- 27677640 TI - Exploring the reasons why pharmacists dispense antibiotics without prescriptions in Khartoum state, Sudan. AB - OBJECTIVES: The principal aim of this study was to explore the perspectives of community pharmacists in Khartoum State, Sudan about why they dispense antibiotics without prescription, and to understand their opinions about why they think patients self-medicate. METHODS: This was a qualitative exploratory interview study. Individual, in-depth face-to-face interviews were conducted with a convenience sample of 30 community pharmacists working in Khartoum State, Sudan in the period from May to June 2015. Each interview was recorded, transcribed, anonymized and coded into themes. Thematic analysis was carried out. KEY FINDINGS: The study revealed that patients' inability to afford consultation fees is the key reason that leads community pharmacists to dispense antibiotics without prescriptions. Other reasons include inaccessible health facilities and long waiting time for consultation, patient being familiar with the symptoms and had previously responded to antibiotic treatment, lack of monitoring of dispensing practices by health authority, commercial interest of pharmacists, blurred professional boundaries between pharmacists and doctors in patients' minds, and lack of pharmacists care regarding educating patients about the impact of self-medication. CONCLUSION: Although different reasons were identified that lead pharmacists to dispense antibiotics without prescription, patients' inability to afford consultation fees remains the key one. It is crucial to address this problem. Improving the accessibility and quality of governmental health facilities, increasing public and pharmacists' awareness about the risks of self-medication and monitoring the dispensing practices at community pharmacies by health authorities are also important. PMID- 27677639 TI - Genomic and functional analysis of the host response to acute simian varicella infection in the lung. AB - Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host. PMID- 27677643 TI - Continuing Medical Education activity in Echocardiography : September 2016. PMID- 27677642 TI - Improved detection of myocardial damage in sarcoidosis using longitudinal strain in patients with preserved left ventricular ejection fraction. AB - BACKGROUND: Cardiac infiltration is an important cause of death in sarcoidosis. Transthoracic echocardiography (TTE) has limited sensitivity for the detection of cardiac sarcoidosis (CS). Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to diagnose CS but has limitations of cost and availability. We sought to determine whether TTE-derived global longitudinal strain (GLS) may be used to identify individuals with CS, despite preserved left ventricular ejection fraction (LVEF), and whether abnormal GLS is associated with major cardiovascular events (MCE). METHODS: We studied 31 patients with biopsy proven extra-cardiac sarcoidosis, LVEF>50% and LGE on CMR (CS+ group), and 31 patients without LGE (CS- group), matched by age, sex, and severity of lung disease. GLS was measured using vendor-independent speckle tracking software. Parameters of left and right ventricular systolic and diastolic function were also studied. Receiver-operating characteristic curves were used to identify GLS cutoff for CS detection, and Kaplan-Meier plots to determine the ability of GLS to predict MCE. RESULTS: LGE was associated with reduced GLS (-19.6+/-1.9% in CS- vs -14.7+/-2.4% in CS+, P<.01) and with reduced E/A ratio (1.1+/-0.3 vs 0.9+/ 0.3, respectively, P =.01). No differences were noted in other TTE parameters. GLS magnitude inversely correlated with LGE burden (r=-.59). GLS cutoff of -17% showed sensitivity and specificity 94% for detecting CS. Patients who experienced MCE had worse GLS than those who did not (-13.4+/-0.9% vs -17.7+/-0.4%, P=.0003). CONCLUSIONS: CS is associated with significantly reduced GLS in the presence of preserved LVEF. GLS measurements may become part of the TTE study performed to screen for CS. PMID- 27677644 TI - Right Ventricular Outflow Tract (RVOT) Changes in Children with an Atrial Septal Defect: Focus on RVOT Velocity Time Integral, RVOT Diameter, and RVOT Systolic Excursion. AB - OBJECTIVE: Aim of the study was to determine the influence of right heart volume overload in children with atrial septal defect (ASD) on right ventricular outflow tract (RVOT) variables. METHODS: A prospective study was conducted in 115 children (age range: 2 days-18.1 years) with a moderate to large ASD. We determined effects of age, body length (BL), body weight (BW), and body surface area (BSA) on the variables RVOT diameter, RVOT velocity time integral (VTI), and RVOT systolic excursion (SE), and tested the predictive value of published normal values for age, BW, BL, and BSA in our ASD patients. RESULTS: In our pediatric ASD patients, the age-specific RVOT diameter (z-score: +2.2, 95% CI: 2.0-2.4, P < 0.001) was significantly increased compared to normal values with 54% of our ASD patients having a z-score >2.0. The age-specific RVOT VTI z-score (z-score: +3.6, 95% CI: 3.2-3.9, P < 0.001) was significantly increased compared to normal values with 81% of our ASD patients having a z-score >2.0. The age-specific RVOT SE z score was not increased but slightly lower compared to normal values (z-score: 0.5, 95% CI: -0.7 to -0.3, P < 0.001) with 3% of our ASD patients having a z score >2.0 while 12% of the patients had a z-score <-2. CONCLUSION: In our study population, we show the RVOT VTI and diameter to be relevant predictors in identifying an enlarged RVOT size and flow in children with moderate to large ASD. PMID- 27677645 TI - A unique case of "double-orifice aortic valve"-comprehensive assessment by 2-, 3 dimensional, and color Doppler echocardiography. AB - Transesophageal echocardiography (TEE) is a powerful imaging tool for the comprehensive assessment of valvular structure and function. TEE may be of added benefit when anatomy is difficult to delineate accurately by transthoracic echocardiography. In this article, we present 2-, 3-dimensional, and color Doppler TEE images from a male patient with aortic stenosis. A highly unusual and complex pattern of valvular calcification created a functionally "double-orifice" valve. Such an abnormality may have implications for the accuracy of continuous wave Doppler echocardiography, which assumes a single orifice valve in native aortic valves. PMID- 27677646 TI - Altitude-induced pulmonary hypertension on one-day rapid ascent of Mount Fuji: incidence and therapeutic effects of sildenafil. PMID- 27677647 TI - Reply. PMID- 27677648 TI - DSM-IV, DSM-5, and ICD-11: Identifying children with posttraumatic stress disorder after disasters. AB - BACKGROUND: Different criteria for diagnosing posttraumatic stress disorder (PTSD) have been recommended by the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the proposed 11th edition of the International Classification of Diseases (ICD-11). Although children are vulnerable to PTSD following disasters, little is known about whether these revised criteria are appropriate for preadolescents, as diagnostic revisions have been based primarily on adult research. This study investigated rates of PTSD using DSM-IV, DSM-5, and ICD-11 diagnostic criteria, and their associations with symptom severity, impairment, and PTSD risk factors. METHODS: Children (7-11 years) exposed to Hurricanes Ike (n = 327) or Charley (n = 383) completed measures 8-9 months postdisaster. Using diagnostic algorithms for DSM-IV, DSM-5, and ICD-11, rates of 'probable' PTSD were calculated. RESULTS: Across samples, rates of PTSD were similar. However, there was low agreement across the diagnostic systems, with about a third overlap in identified cases. Children identified only by ICD-11 had higher 'core' symptom severity but lower impairment than children identified only by DSM-IV or DSM-5. ICD-11 was associated with more established risk factors for PTSD than was DSM-5. CONCLUSIONS: Findings revealed differences in PTSD diagnosis across major diagnostic systems for preadolescent children, with no clear advantage to any one system. Further research on developmentally sensitive PTSD criteria for preadolescent children is needed. PMID- 27677649 TI - Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31 mediated cell elongation in mycobacteria. AB - There is an urgent need to discover new anti-tubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that has potent, bactericidal activity against M. tuberculosis. Mutations in APYS1-resistant M. tuberculosis mapped exclusively to wag31, a gene that encodes a scaffolding protein thought to orchestrate cell elongation. Recombineering confirmed that a Gln201Arg mutation in Wag31 was sufficient to cause resistance to APYS1, however, neither overexpression nor conditional depletion of wag31 impacted M. tuberculosis susceptibility to this compound. In contrast, expression of the wildtype allele of wag31 in APYS1-resistant M. tuberculosis was dominant and restored susceptibility to APYS1 to wildtype levels. Time-lapse imaging and scanning electron microscopy revealed that APYS1 caused gross malformation of the old pole of M. tuberculosis, with eventual lysis. These effects resembled the morphological changes observed following transcriptional silencing of wag31 in M. tuberculosis. These data show that Wag31 is likely not the direct target of APYS1, but the striking phenotypic similarity between APYS1 exposure and genetic depletion of Wag31 in M. tuberculosis suggests that APYS1 might indirectly affect Wag31 through an as yet unknown mechanism. PMID- 27677651 TI - Comparing the effectiveness of pharmacist-managed warfarin anticoagulation with other models: a systematic review and meta-analysis. AB - WHAT IS KNOWN AND OBJECTIVE: Anticoagulation management services are well known to improve the quality of patient care and to reduce the rates of hospitalization and emergency department visits following adverse events related to anticoagulation therapy. The complexity of managing warfarin has led to the development of a variety of specialized models managed by pharmacists, physicians, nurses, and self-managed care. The aim of the study is to compare the effectiveness of pharmacist-managed anticoagulation control of warfarin with other models. METHODS: We performed a systematic literature search of the PubMed, Medline@Web of Knowledge, EMBASE, Cochrane Library and Cumulative Index to Nursing and Allied Health Literature to identify randomized controlled trials (RCTs) from database inception up to July 2015. The search terms used for the study were 'warfarin', 'pharmacists', 'Vitamin K antagonist', 'anticoagulation' and 'management model.' We used the Cochrane Collaboration's tool from the Cochrane Handbook to assess the risk of bias of RCTs. We performed statistical analyses using RevMan 5.3 and used the Grading of Recommendations, Assessment, Development, and Evaluations profiler to rate the quality of evidence of the outcomes. The anticoagulation control outcomes were the percentage of time within the standard and expanded therapeutic range and thrombosis events; the safety outcomes were bleeding events and mortality, and patients' satisfaction of anticoagulation service. RESULTS AND DISCUSSION: Eight RCTs from 981 potentially relevant publications with a total of 1493 patients were included. Meta-analysis of the RCTs showed that a significant difference existed between pharmacist managed care and other models for satisfaction (mean difference (MD) = 0.41, 95% CI, 0.01-0.81, P = 0.04, low-quality evidence) with heterogeneity, and the percentage of time within the standard therapeutic range (MD = 3.66, 95% CI 2.20 5.11, P < 0.00001, high-quality evidence) without heterogeneity. However, the pharmacist-managed group demonstrated no significant improvement on the percentage of time within the expanded therapeutic range (MD = 2.85, 95% CI -0.56 to 6.26, P = 0.10, moderate-quality evidence) with heterogeneity, mortality [odds ratio (OR) = 0.97, 95% CI, 0.44-2.11, P = 0.09, high-quality evidence] without heterogeneity, the prevention of bleeding events (OR = 0.89, 95% CI, 0.56-1.44, P = 0.64, high-quality evidence) without heterogeneity, and thrombosis events (OR = 0.81, 95% CI, 0.34-1.92, P = 0.64, high-quality evidence) without heterogeneity. WHAT IS NEW AND CONCLUSION: The advantage of pharmacist-managed warfarin anticoagulation therapy in terms of anticoagulation control, safety and mortality are unclear, but resulted in significantly better patient satisfaction. Compared with other models, the superiority of pharmacist-managed warfarin anticoagulation needs to be further evaluated and validated in future research. PMID- 27677650 TI - Inhibitory effect of high-frequency greater occipital nerve electrical stimulation on trigeminovascular nociceptive processing in rats. AB - Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura sensitive STN neurons. The experiments were carried out on urethane/chloralose anesthetized, paralyzed and artificially ventilated male Wistar rats. Extracellular recordings were made from 11 neurons within the caudal part of the STN that received convergent input from the ipsilateral facial cutaneous receptive fields, dura mater and GON. In each experiment, five various combinations of the GON stimulation frequency (50, 75, 100 Hz) and intensity (1, 3, 6 V) were tested successively in 10 min interval. At all parameter sets, preconditioning GON stimulation (250 ms train of pulses applied before each recording) produced suppression of both the ongoing activity of the STN neurons and their responses to electrical stimulation of the dura mater. The inhibitory effect depended mostly on the GON stimulation intensity, being maximally pronounced when a stimulus of 6 V was applied. Thus, the GON stimulation-induced inhibition of trigeminovascular nociceptive processing at the level of STN has been demonstrated for the first time. The data obtained can contribute to a deeper understanding of neurophysiological mechanisms underlying the therapeutic efficacy of GON stimulation in primary headaches. PMID- 27677652 TI - Low mitochondrial DNA diversity of Japanese Polled and Kuchinoshima feral cattle. AB - This study aims to estimate the mitochondrial genetic diversity and structure of Japanese Polled and Kuchinoshima feral cattle, which are maintained in small populations. We determined the mitochondrial DMA (mtDNA) displacement loop (D loop) sequences for both cattle populations and analyzed these in conjunction with previously published data from Northeast Asian cattle populations. Our findings showed that Japanese native cattle have a predominant, Asian-specific mtDNA haplogroup T4 with high frequencies (0.43-0.81). This excluded Kuchinoshima cattle (32 animals), which had only one mtDNA haplotype belonging to the haplogroup T3. Japanese Polled showed relatively lower mtDNA diversity in the average sequence divergence (0.0020) than other Wagyu breeds (0.0036-0.0047). Japanese Polled have been maintained in a limited area of Yamaguchi, and the population size is now less than 200. Therefore, low mtDNA diversity in the Japanese Polled could be explained by the decreasing population size in the last three decades. We found low mtDNA diversity in both Japanese Polled and Kuchinoshima cattle. The genetic information obtained in this study will be useful for maintaining these populations and for understanding the origin of Japanese native cattle. PMID- 27677653 TI - Phenylalkylamine Passivation of Organolead Halide Perovskites Enabling High Efficiency and Air-Stable Photovoltaic Cells. AB - Benzylamine is introduced as a surface passivation molecule that improves the moisture-resistance of the perovskites while simultaneously enhancing their electronic properties. Solar cells based on benzylamine-modified formamidinium lead iodide perovskite films exhibit a champion efficiency of 19.2% and an open circuit voltage of 1.12 V. The modified FAPbI3 films exhibit no degradation after >2800 h air exposure. PMID- 27677655 TI - Horizontal root fractures in posterior teeth without dental trauma: tooth/root distribution and clinical characteristics. AB - AIM: To describe the clinical characteristics and radiographic findings of horizontal root fractures (HRF) in posterior teeth without a history of dental trauma. METHODOLOGY: A total 24 patients and 31 HRF cases in 28 posterior teeth were collected from 2006 to 2015. Clinical examinations and radiographic imaging were evaluated. Value of confidence intervals of the proportions was calculated for data presentation. RESULTS: The number of males (54%) was similar to females (46%). The patients were predominantly between 50 and 70 years of age (75%). Most HRF cases were found in nonendodontically treated teeth (79%), without crown and bridge restorations (82%), and maxillary molars (54%). Many roots of maxillary molars had developed HRF, and the probability was nearly equal. Fractured teeth usually presented with periodontal and apical bone loss, and most patients (92%) were diagnosed with full mouth chronic periodontitis. Tooth wear was another common clinical feature amongst these patients. CONCLUSIONS: HRF in posterior teeth without dental trauma occurred mainly in patients aged between 50 and 70, in nonendodontically treated teeth, teeth with attrition but without crown and bridge restorations, maxillary molars and with periodontal and periapical bony destruction. Periodontal condition, occlusal wear and patients' age at diagnosis were the possible related factors. HRF in posterior teeth without dental trauma is a diagnostic challenge and even misdiagnosed. A thorough clinical examination, radiographic analysis and recognition of the clinical characteristics are helpful in the early diagnosis and treatment of HRF. PMID- 27677654 TI - Inhibition of cytokine response to TLR stimulation and alleviation of collagen induced arthritis in mice by Schistosoma japonicum peptide SJMHE1. AB - Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA). We show that SJMHE1 not only modulates the cytokine production of murine macrophage (MPhi) and dendritic cell but also affects cytokine production upon coculturing with allogeneic CD4+ T cell. SJMHE1 potently inhibits the cytokine response to TLR ligands lipopolysaccharide (LPS), CpG oligodeoxynucleotides (CpG) or resiquimod (R848) from mouse splenocytes, and human PBMCs stimulated by LPS. Furthermore, SJMHE1 suppressed clinical signs of CIA in mice and blocked joint erosion progression. This effect was mediated by downregulation of key cytokines involved in the pathogenesis of CIA, such as interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-17, and IL-22 and up regulation of the inhibitory cytokine IL-10, Tgf-beta1 mRNA, and CD4+ CD25+ Foxp3+ Tregs. This study provides new evidence that the peptide from S. japonicum, which is the 'safe' selective generation of small molecule peptide that has evolved during host-parasite interactions, is of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases. PMID- 27677656 TI - How to facilitate early diagnosis of CNS involvement in malignant lymphoma. AB - INTRODUCTION: Making the diagnosis of secondary CNS involvement in lymphoma can be difficult due to unspecific signs and symptoms, limited accessibility of brain/myelon parenchyma and low sensitivity and/or specifity of imaging and cerebrospinal fluid (CSF) examination currently available. Areas covered: MRI of the total neuroaxis followed by CSF cytomorphology and flow cytometry are methods of choice when CNS lymphoma (CNSL) is suspected. To reduce the numerous pitfalls of these examinations several aspects should be considered. New CSF biomarkers might be of potential diagnostic value. Attempts to standardize response criteria are presented. Expert commentary: Diagnosing CNSL remains challenging. Until diagnostic methods combining high sensitivity with high specifity are routinely introduced, high level of awareness and optimal utilization of examinations currently available are needed to early diagnose this potentially devastating disease. PMID- 27677657 TI - [Identification of Mycobacteria isolated from AIDS patients]. AB - Obstract: To identify Mycobacteria isolated from AIDS patients and to evaluate the diagnostic value of MBP64 antigen Colloidal Gold Diagnostic Kit in distinguishing Mycobacterium tuberculosis(MTB) and Nontuberculous mycobacteria (NTM). Methods: A total of 140 Mycobacteria isolates from AIDS patients were collected and identified by using 16SrDNA PCR assay as well as immune colloidal gold technique (MBP64 antigen Colloidal Gold Diagnostic Kit). The sensitivity and specificity of Colloidal Gold method was analyzed. Results: With the results of 16SrDNA PCR assay as gold standard, the sensitivity and specificity of Colloidal Gold method in distinguishing MTB and NTM were 96.00% and 96.84%, respectively. Among 140 samples, 114 were identified by 16SrDNA PCR assay, among which 50 (43.86%) were identified as MTB, and 63 (55.26%) were identified as NTM. The most popular NTM in AIDS patients were Mycobacterium gordonae, Mycobacterium avium and Mycobacterium kansasii. Conclusion: NTM is of high prevalence in AIDS patients, and MBP64 antigen Colloidal Gold Diagnostic Kit can be used as an effective technique in distinguishing NTM and MTB. PMID- 27677660 TI - Attitudes toward participating in Phase I clinical trials: an investigation with patient-family-physician triads. AB - OBJECTIVE: Phase I oncology trials have raised concerns that patients' 'unrealistic' optimism could compromise the validity of informed consent, and that patients often participate in trials to conform to physicians' or family members' recommendations. We aimed to determine whether patients or families given the same information of risk-benefit profile-are more likely to participate in Phase I trials than their physicians and whether people in family or physician situations are more likely to recommend trial participation to patients than they would want for themselves as patients. METHODS: We conducted a hypothetical vignette study with a patient-caregiver-oncologist. Three groups-725 patient caregiver pairs recruited by 134 oncologists-were asked to assume three different roles as patients, caregivers and physicians and provided a scenario of a hypothetical patient with treatment-resistant cancer. They were asked questions regarding their intention to participate in or to recommend a Phase I clinical trial. RESULTS: Acceptance rates of the trial were as follows: (a) in the patients' role: patients (54.1), caregivers (62.3) and physicians (63.4%); (b) in the caregivers' role: 55.6, 64.7 and 70.9%; (c) in the physicians' role: 66.1, 70.8 and 76.1%. Patients or caregivers were not more positive to the trial than physicians. All three groups showed more positive attitudes toward the clinical trial when they assumed the role of caregiver or physician than that of patient. CONCLUSIONS: Patients and caregivers seem to make as reasonable decisions as physicians; patients seem to take family members' or physicians' recommendation as their legitimate roles rather than as undue pressure. PMID- 27677661 TI - Treatment strategy for hepatocellular carcinoma in China: radiofrequency ablation versus liver resection. AB - Hepatocellular carcinoma is the most common malignancy in liver, is also a global problem and is the fourth most commonly diagnosed cancers among men and the fourth leading causes of cancer death among both men and women in China. Liver resection or hepatic resection and radiofrequency ablation is widely accepted as a first-line surgical approach for hepatocellular carcinoma in China. However, the indications of radiofrequency ablation or hepatic resection are different and not unified in China. In this article, we review the current status of hepatic resection and radiofrequency ablation therapies in hepatocellular carcinoma management in China. PMID- 27677662 TI - Quality of life and functional status of terminally ill head and neck cancer patients: a nation-wide, prospective observational study at tertiary cancer centers in Japan. AB - BACKGROUND: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers. METHODS: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients. RESULTS: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372). CONCLUSION: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life. PMID- 27677663 TI - Respiration-gated fast-rescanning carbon-ion radiotherapy. AB - Phase-controlled rescanning of the carbon-ion beam offers fast and precise dose application with decreased irradiation of normal tissue. However, organ movement with respiration remains a unique challenge. Technological development has enabled the simultaneous application of beam-energy-modulated markerless phase controlled rescanning with respiration gating, allowing scanning treatment of respiration-mobile tumors with carbon. A total of 10 patients with tumors in the liver or lung were treated in a feasibility study at our facility using this combination. At a median of 10.5 months, follow-up examination including computed tomography/magnetic resonance imaging revealed no grade 2+ acute adverse effects with this new therapy. Two patients with complex disease experienced local recurrence, which may be improved with increased dose delivery. One patient died of unrelated causes. All other patients are alive with good control at the time of writing. Though long-term observation is pending, these are promising initial results for use of the carbon-beam phase-controlled rescanning method in respiration-mobile disease. PMID- 27677665 TI - Evaluating the potential carcinogenic hazard of glyphosate. PMID- 27677664 TI - Adjuvant therapy after radical surgery for stage IB-IIB cervical adenocarcinoma with risk factors. AB - OBJECTIVE: Patients with adeno/adenosquamous carcinoma may have a poorer prognosis than patients with squamous cell carcinoma. Radiotherapy and concurrent chemoradiotherapy are used as adjuvant therapies for cervical cancer, regardless of the histological subtype. The aim of this study was to investigate the prognostic outcome of adjuvant therapy for patients with adeno/adenosquamous carcinoma with pathological risk factors. METHODS: The medical records of 135 patients with stage IB-IIB cervical cancer with squamous cell carcinoma or adeno/adenosquamous carcinoma who underwent primary surgery followed by adjuvant therapy were retrospectively reviewed. Patients with a pathologically confirmed bulky tumor (>=4 cm), nodal metastasis and/or parametrium invasion were included in the study. RESULTS: The median follow-up period was 48 (1-132) months. Of the 135 patients, 90 with squamous cell carcinoma and 23 with adeno/adenosquamous carcinoma were treated with adjuvant radiotherapy and concurrent chemoradiotherapy (SCC-RT/CCRT and AC-RT/CCRT groups), and 22 with adeno/adenosquamous carcinoma were treated with adjuvant systemic chemotherapy (AC-CT group). There were no significant differences in clinicopathological factors between the SCC-RT/CCRT and AC-RT/CCRT groups and between the AC-RT/CCRT and AC-CT groups. Progression-free survival was significantly shorter in the AC RT/CCRT group compared to the SCC-RT/CCRT group (P = 0.002). Adeno/adenosquamous carcinoma histology and multiple lymph node metastasis were independent prognostic factors for shorter progression-free survival in patients treated with adjuvant radiotherapy and concurrent chemoradiotherapy. Progression-free survival was also significantly shorter in the AC-RT/CCRT group compared to the AC-CT group (P = 0.026). CONCLUSIONS: Adjuvant radiotherapy and concurrent chemoradiotherapy may be less effective for patients with adeno/adenosquamous carcinoma than for those with squamous cell carcinoma. Adjuvant systemic chemotherapy may be beneficial for adeno/adenosquamous carcinoma and further studies are warranted. PMID- 27677666 TI - A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment. AB - The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans. PMID- 27677667 TI - Glyphosate in the general population and in applicators: a critical review of studies on exposures. AB - The recent classification of glyphosate as a probable human carcinogen by the International Agency for Research on Cancer (IARC) was arrived at without a detailed assessment of exposure. Glyphosate is widely used as an herbicide, which might result in exposures of the general public and applicators. Exposures were estimated from information in the open literature and unpublished reports provided by Monsanto Company. Based on the maximum measured concentration in air, an exposure dose of 1.04 * 10 - 6 mg/kg body mass (b.m.)/d was estimated. Assuming consumption of surface water without treatment, the 90th centile measured concentration would result in a consumed dose of 2.25 * 10 - 5 mg/kg b.m./d. Estimates by the Food and Agriculture Organization of the United Nations (FAO) of consumed doses in food provided a median exposure of 0.005 mg/kg b.m./d (range 0.002-0.013). Based on tolerance levels, the conservative estimate by the US Environmental Protection Agency (US EPA) for exposure of the general population via food and water was 0.088 mg/kg b.m./d (range 0.058-0.23). For applicators, 90th centiles for systemic exposures based on biomonitoring and dosimetry (normalized for penetration through the skin) were 0.0014 and 0.021 mg/kg b.m./d, respectively. All of these exposures are less than the reference dose and the acceptable daily intakes proposed by several regulatory agencies, thus supporting a conclusion that even for these highly exposed populations the exposures were within regulatory limits. PMID- 27677668 TI - Glyphosate epidemiology expert panel review: a weight of evidence systematic review of the relationship between glyphosate exposure and non-Hodgkin's lymphoma or multiple myeloma. AB - We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) - two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses. Our evaluation included seven unique studies for NHL and four for MM, all but one of which were case control studies for each cancer. For NHL, the case-control studies were all limited by the potential for recall bias and the lack of adequate multivariate adjustment for multiple pesticide and other farming exposures. Only the Agricultural Health (cohort) Study met our a priori quality standards and this study found no evidence of an association between glyphosate and NHL. For MM, the case control studies shared the same limitations as noted for the NHL case control studies and, in aggregate, the data were too sparse to enable an informed causal judgment. Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM. PMID- 27677669 TI - Glyphosate rodent carcinogenicity bioassay expert panel review. AB - Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals. PMID- 27677670 TI - Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid. AB - In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extensive reviews supporting the lack of genotoxicity of glyphosate and glyphosate formulations. The IARC Monograph concluded there was strong evidence of induction of oxidative stress by glyphosate, glyphosate formulations, and AMPA. The Expert Panel reviewed the genotoxicity and oxidative stress data considered in the IARC Monograph, together with other available data not considered by IARC. The Expert Panel defined and used a weight of evidence (WoE) approach that included ranking of studies and endpoints by the strength of their linkage to events associated with carcinogenic mechanisms. Importantly, the Expert Panel concluded that there was sufficient information available from a very large number of regulatory genotoxicity studies that should have been considered by IARC. The WoE approach, the inclusion of all relevant regulatory studies, and some differences in interpretation of individual studies led to significantly different conclusions by the Expert Panel compared with the IARC Monograph. The Expert Panel concluded that glyphosate, glyphosate formulations, and AMPA do not pose a genotoxic hazard and the data do not support the IARC Monograph genotoxicity evaluation. With respect to carcinogenicity classification and mechanism, the Expert Panel concluded that evidence relating to an oxidative stress mechanism of carcinogenicity was largely unconvincing and that the data profiles were not consistent with the characteristics of genotoxic carcinogens. PMID- 27677671 TI - Delayed Response to Corpus Callosotomy. PMID- 27677672 TI - Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents. AB - The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans. PMID- 27677673 TI - Large field-of-view movement-compensated intrinsic optical signal imaging for the characterization of the haemodynamic response to spreading depolarizations in large gyrencephalic brains. AB - Haemodynamic responses to spreading depolarizations (SDs) have an important role during the development of secondary brain damage. Characterization of the haemodynamic responses in larger brains, however, is difficult due to movement artefacts. Intrinsic optical signal (IOS) imaging, laser speckle flowmetry (LSF) and electrocorticography were performed in different configurations in three groups of in total 18 swine. SDs were elicited by topical application of KCl or occurred spontaneously after middle cerebral artery occlusion. Movement artefacts in IOS were compensated by an elastic registration algorithm during post processing. Using movement-compensated IOS, we were able to differentiate between four components of optical changes, corresponding closely with haemodynamic variations measured by LSF. Compared with ECoG and LSF, our setup provides higher spatial and temporal resolution, as well as a better signal-to-noise ratio. Using IOS alone, we could identify the different zones of infarction in a large gyrencephalic middle cerebral artery occlusion pig model. We strongly suggest movement-compensated IOS for the investigation of the role of haemodynamic responses to SDs during the development of secondary brain damage and in particular to examine the effect of potential therapeutic interventions in gyrencephalic brains. PMID- 27677676 TI - Early second-trimester plasma levels of NT-proBNP in women who subsequently develop early-onset preeclampsia. AB - Plasma levels of NT-proBNP are elevated in women with preeclampsia at the time of diagnosis. The objective of this case-control study was to evaluate N-terminal proBNP (NT-proBNP) in maternal plasma as an early second-trimester biomarker for prediction of early-onset preeclampsia. In early second-trimester samples, women who later developed preeclampsia at gestational age 34 wk + 0 or earlier (n = 16) had similar plasma levels of NT-proBNP (median 51.8, range 26.1-131.9 pg/ml) as women with uncomplicated pregnancy outcomes (n = 43) (53.0, 14.9-184.2 pg/ml). The early second-trimester level of NT-proBNP cannot therefore be used as a predictive biomarker of early-onset preeclampsia. PMID- 27677675 TI - Evolution of severe sleep-wake cycle disturbances following traumatic brain injury: a case study in both acute and subacute phases post-injury. AB - BACKGROUND: Sleep-wake disturbances are frequently reported following traumatic brain injury (TBI), but they remain poorly documented in the acute stage of injury. Little is known about their origin and evolution. CASE PRESENTATION: This study presents the case of a patient in the acute phase of a severe TBI. The patient was injured at work when falling 12 m into a mine and was hospitalized in the regular wards of a level I trauma centre. From days 31 to 45 post-injury, once he had reached a level of medical stability and continuous analgosedation had been ceased, his sleep-wake cycle was monitored using actigraphy. Results showed significant sleep-wake disturbances and severe sleep deprivation. Indeed, the patient had an average nighttime sleep efficiency of 32.7 +/- 15.4 %, and only an average of 4.8 +/- 1.3 h of sleep per 24-h period. After hospital discharge to the rehabilitation centre, where he remained for 5 days, the patient was readmitted to the same neurological unit for paranoid delusions. During his second hospital stay, actigraphy recordings resumed from days 69 to 75 post injury. A major improvement in his sleep-wake cycle was observed during this second stay, with an average nighttime sleep efficiency of 96.3 +/- 0.9 % and an average of 14.1 +/- 0.9 h of sleep per 24-h period. CONCLUSION: This study is the first to extensively document sleep-wake disturbances in both the acute and subacute phases of severe TBI. Results show that prolonged sleep deprivation can be observed after TBI, and suggest that the hospital environment only partially contributes to sleep-wake disturbances. Continuous actigraphic monitoring may prove to be a useful clinical tool in the monitoring of patients hospitalized after severe TBI in order to detect severe sleep deprivation requiring intervention. The direct impact of sleep-wake disturbances on physiological and cognitive recovery is not well understood within this population, but is worth investigating and improving. PMID- 27677674 TI - Mitochondrial fission and fusion in secondary brain damage after CNS insults. AB - Mitochondria are dynamically active organelles, regulated through fission and fusion events to continuously redistribute them across axons, dendrites, and synapses of neurons to meet bioenergetics requirements and to control various functions, including cell proliferation, calcium buffering, neurotransmission, oxidative stress, and apoptosis. However, following acute or chronic injury to CNS, altered expression and function of proteins that mediate fission and fusion lead to mitochondrial dynamic imbalance. Particularly, if the fission is abnormally increased through pro-fission mediators such as Drp1, mitochondrial function will be impaired and mitochondria will become susceptible to insertion of proapototic proteins. This leads to the formation of mitochondrial transition pore, which eventually triggers apoptosis. Thus, mitochondrial dysfunction is a major promoter of neuronal death and secondary brain damage after an insult. This review discusses the implications of mitochondrial dynamic imbalance in neuronal death after acute and chronic CNS insults. PMID- 27677677 TI - Molecular dynamics-based analyses of the structural instability and secondary structure of the fibrinogen gamma chain protein with the D356V mutation. AB - Mutations in the fibrinogen gamma chain (FGG) gene have been associated with various disorders, such as dysfibrinogenemia, thrombophilia, and hypofibrinogenemia. A literature survey showed that a residue exchange in fibrinogen Milano I from gamma Asp to Val at position 330 impairs fibrin polymerization. The D356V (D330V) mutation located in the C-terminus was predicted to be highly deleterious and to affect the function of the protein. The pathogenicity of the altered gene and changes in protein functions were predicted using in silico methods, such as SIFT, PolyPhen 2, I-Mutant 3.0, Align GV-GD, PhD SNP, and SNPs&GO. The secondary structure of the mutant protein was unwound by the end of the 50-ns simulation period, and a structural change in the helix-turn transition of the alpha-helical (352-356) region residues was observed. Moreover, a change in the length of the helical region was visualized in the mutant trajectory file, indicating the local transient unfolding of the protein. The obtained computational results suggest that the substitution of the neutral amino acid valine for the acidic amino acid aspartic acid at position 356 results in an unwound conformation within 50 ns, which might contribute to defective polymerization. Our analysis also provides insights into the effect of the conformational change in the D356V (D330V) mutant on protein structure and function. PMID- 27677678 TI - Application and outcomes of therapy combining transcranial direct current stimulation and virtual reality: a systematic review. AB - PURPOSE: To evaluate the methods and major outcomes of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) therapy in randomized controlled trials. METHOD: A systematic review was performed following PRISMA guidelines using PubMed, PubMed Central, Web of Science and CAPES periodic databases, with no time restriction. The studies were screened for the following inclusion criteria: human subjects, combination of VR and tDCS methods, and randomized controlled study design. All potentially relevant articles were independently reviewed by two researchers, who reached a consensus on which articles met the inclusion criteria. The PEDro scale was used to evaluate the studies. RESULTS: Eleven studies were included, all of which utilized a variety of tDCS and VR application methods. The main outcomes were found to be beneficial in intervention groups of different populations, including improvements in body sway, gait, stroke recovery, pain management and vegetative reactions. CONCLUSIONS: The use of tDCS combined with VR showed positive results in both healthy and impaired patients. Future studies with larger sample sizes and homogeneous participants are required to confirm the benefits of tDCS and VR. Implications for Rehabilitation tDCS with VR intervention can be an alternative to traditional rehabilitation programs. tDCS with VR is a promising type of intervention with a variety of positive effects. Application of tDCS with VR is appropriated to both healthy and impaired patients. There is no consensus of tDCS with VR application. PMID- 27677679 TI - Immunoglobulin heavy light chain test quantifies clonal disease in patients with AL amyloidosis and normal serum free light chain ratio. AB - BACKGROUND: Serum and urine immunofixation electrophoreses (SIFE/UIFE) are used for clonal detection in plasma cell dyscrasias, while serum free light chain (sFLC) testing provides quantitation of clonal disease. Up to 20% of patients with light chain (AL) amyloidosis may present with normal FLC ratio (FLCr). METHODS: We assessed the diagnostic, quantitative and prognostic potential of serum heavy light chain ratio (HLCr) in 199 untreated patients at initial evaluation. RESULTS: An abnormal HLCr was found in 37.2%, abnormal FLCr in 81.9% and positivity by SIFE/UIFE in 94% of patients. HLCr together with SIFE/UIFE identified clonality in 94% patients; the combination with FLCr yielded 100% sensitivity. An HLCr abnormality was significantly over-represented in normal compared to abnormal FLCr group (63.9% versus 31.3%). HLCr did not predict overall survival (OS) (log rank, p = 0.09), while an abnormal FLCr was associated with decreased OS (log rank, p = 0.03). The combined use of both ratios trended toward increased OS in the abnormal HLCr/normal FLCr group (log rank, p = 0.11; Wilcoxon, p = 0.04). On multivariate analysis, HLCr was not predictive of OS, whereas an abnormal FLCr was associated with shorter OS (HR = 1.7, p = 0.04). CONCLUSIONS: The HLC assay has potential as a supplemental test to quantify monoclonal protein in patients with normal FLCr results. PMID- 27677680 TI - Expression and functional characterization of interferon regulatory factors (irf2, irf7 and irf9) in the blunt snout bream (Megalobrama amblycephala). AB - Interferon regulatory factors (irfs) are a family of genes that encode transcription factors with important roles in regulating the expression of Type I interferons (IFNs) and other genes associated with related pathways. irfs have multitudinous functions in growth, development and regulation of oncogenesis. In this study, three irf family members (irf2, irf7, irf9) were identified and characterized in Megalobrama amblycephala at the mRNA and amino acid levels. M. amblycephala irfs share a high sequence homology with other vertebrate irfs. Constitutive expression levels of the three genes were detected (using qPCR) in all studied tissues: low to medium in kidney, gills, heart and muscle, and high in liver, spleen, intestine and blood. qPCR was also used to analyze the dynamic expression patterns of irfs in different embryonic development stages: irf2 is not activated during the embryonic development, whereas irf9 appears to play important roles around hatching and during the larval development. Transcripts of all three studied irfs were upregulated after stimulation by Aeromonas hydrophila bacterium in liver, spleen, head kidney and trunk kidney, whereas downregulation was observed in intestine and gills. The results show that these three irfs are likely to be important factors in the blunt snout bream immune system. They also provide a foundation for studying the origin and evolution of the innate immune system in the blunt snout bream. PMID- 27677681 TI - Diversity and temporal patterns of planktonic protist assemblages at a Mediterranean Long Term Ecological Research site. AB - We tracked temporal changes in protist diversity at the Long Term Ecological Research (LTER) station MareChiara in the Gulf of Naples (Mediterranean Sea) on eight dates in 2011 using a metabarcoding approach. Illumina analysis of the V4 and V9 fragments of the 18S rDNA produced 869 522 and 1 410 071 sequences resulting in 6517 and 6519 OTUs, respectively. Marked compositional variations were recorded across the year, with less than 2% of OTUs shared among all samples and similar patterns for the two marker tags. Alveolata, Stramenopiles and Rhizaria were the most represented groups. A comparison with light microscopy data indicated an over-representation of Dinophyta in the sequence dataset, whereas Bacillariophyta showed comparable taxonomic patterns between sequence and light microscopy data. Shannon diversity values were stable from February to September, increasing thereafter with a peak in December. Community variance was mainly explained by seasonality (as temperature), trophic status (as chlorophyll a), and influence of coastal waters (as salinity). Overall, the background knowledge of the system provided a sound context for the result interpretation, showing that LTER sites provide an ideal setting for high-throughput sequencing (HTS) metabarcoding characterisation of protist assemblages and their relationships with environmental variations. PMID- 27677682 TI - Use of MALDI-TOF mass spectrometry after liquid enrichment (BD BactecTM) for rapid diagnosis of bone and joint infections. AB - Advantages of MALDI-TOF MS (MS) were evaluated for diagnosis of bone and joint infections after enrichment of synovial fluid (SF) or crushed osteoarticular samples (CSs). MS was performed after enrichment of SF or crushed osteoarticular samples CS (n = 108) in both aerobic and anaerobic vials. Extraction was performed on 113 vials (SF: n = 47; CS: n = 66), using the Sepsityper(r) kit prior identification by MS. The performances of MS, score and reproducibility results on bacterial colonies from blood agar and on pellets after enrichment in vials, were compared. MS analysis of the vial resulted in correct identification of bacteria at a species and genus level (80.5% and 92% of cases, respectively). The reproducibility was superior for aerobic Gram-positive bacteria (Staphylococci and Gram-positive bacilli: 100% colonies), as compared to aerobic Gram-negative bacilli (89.7%), anaerobes (83.3%) and Streptococcus/Enterococcus (58.8%). MS performance was significantly better for staphylococci than for streptococci on all identification parameters. For polymicrobial cultures, identification (score>1.5) of two species by MS was acceptable in 92.8% of cases. Use of MS on enrichment pellets of bone samples is an accurate, rapid and robust method for bacterial identification of clinical isolates from osteoarticular infections, except for streptococci, whose identification to species level remains difficult. PMID- 27677683 TI - Oral Surgical Treatment of Patients With Chronic Liver Disease: Assessments of Bleeding and Its Relationship With Thrombocytopenia and Blood Coagulation Parameters. AB - PURPOSE: Cirrhotic patients awaiting liver transplantation require eradication of infectious oral foci to prevent septic episodes after transplantation; however, cirrhosis can hinder hemostasis and can result in severe bleeding. The present study assessed the bleeding risk factors connected with the clinical history of these patients and the characteristics of the extractions. MATERIALS AND METHODS: We retrospectively analyzed 1183 extractions in 318 patients, including 47 with severe end-stage liver disease who were outside of our intention-to-treat bracket (ie, platelet count [PLT] >40 * 103/MUL and international normalized ratio [INR] <2.5). Follow-up examinations included inspection of the oral cavity on the first, third, and seventh days, with reparatory surgery in the case of severe bleeding. Continuous variables were compared using the Mann-Whitney U and Kruskal Wallis tests, and categorical variables were compared using Fisher's exact test. Binary logistic regression analysis was also performed. RESULTS: Within the intention-to-treat bracket, 1 of the 271 patients (0.4%) required surgical repair. The bleeding rate for an INR of 2.5 or more was significantly greater than that for a PLT of 40 * 103/MUL or less (4 of 10 [40%] versus 2 of 34 [6%]; P = .02]. All 3 patients with both an INR of 2.5 or more and a PLT of 40 * 103/MUL or less exhibited severe bleeding. No significant association between the occurrence of bleeding with either liver disease etiology or the number of molars extracted was found. No patient required hospitalization. CONCLUSIONS: Patients with a PLT greater than 40 * 103/MUL and an INR of less than 2.5 can be considered relatively low-risk patients. However, an INR of 2.5 or more and, to a minor degree, a PLT of 40 * 103/MUL or less represent significant risk factors. PMID- 27677684 TI - Surgical Treatment, Oral Rehabilitation, and Orthognathic Surgery After Failure of Pharmacologic Treatment of Central Giant Cell Lesion: A Case Report. AB - Although pharmacologic treatments for central giant cell lesions have gained much emphasis, these treatment modalities do not always have successful outcomes, and surgical treatment may be necessary. The purpose of the present study was to report a case of aggressive central giant cell lesion initially treated by nonsurgical methods without satisfactory results, necessitating segmental mandibular resection for definitive treatment and oral rehabilitation. A 20-year old woman was diagnosed with an aggressive central giant cell lesion in the mandible. The patient was first treated with intralesional corticosteroid injections. Subsequently, the lesion increased in size. Therefore, a second pharmacologic treatment was proposed with salmon calcitonin nasal spray, but no signs of a treatment response were noted. Because of the lack of response, surgical excision was performed, and a mandibular reconstruction plate was installed. At 12 months after surgical resection, the patient underwent mandibular reconstruction with bone grafts. After 6 months, 7 dental implants were installed, and fixed prostheses were made. After installation of the prostheses, the patient experienced persistent mandibular laterognathism, and a mandibular orthognathic surgery was performed to correct the laterognathia. The follow-up examination 4 years after orthognathic surgery showed no signs of recurrence and good facial symmetry. PMID- 27677685 TI - Combined Use of Facial Osteoplasty and Orthognathic Surgery for Treatment of Dentofacial Deformities. AB - PURPOSE: Orthognathic surgery is an efficient procedure for cosmetic and functional aims. However, when functional improvement is achieved by mandibular or maxillary operations, additional esthetic corrections may be imperative for some patients. This study aims to introduce our primary practice of simultaneous facial bone contouring and orthognathic surgery for esthetic reasons. PATIENTS AND METHODS: Ten patients with dentofacial deformities as well as a prominent angle, asymmetric deformities, or a high zygoma and zygomatic arch were recruited from West China Hospital of Stomatology, Sichuan University (Chengdu, China), between January 1, 2014, and July 31, 2015. Traditional orthognathic surgical procedures such as bilateral sagittal split osteotomy and Le Fort I osteotomy combined with facial osteoplasty including mandibular angle ostectomy, outer cortex ostectomy of the mandibular angle, and zygoma and zygomatic arch reduction were performed. Radiographs and medical photographs were taken before and after surgery to compare the effectiveness of the combined use of facial osteoplasty and orthognathic surgery. RESULTS: All patients had an uneventful postoperative recovery, with no signs of infection, jaw displacement, or osteonecrosis. Radiographs taken 1 week after surgery and pictures of the facial profile and occlusion taken 6 months after surgery showed satisfactory esthetic outcomes. All patients were satisfied with the functional and cosmetic results. CONCLUSIONS: This study indicated the clinical feasibility of simultaneous facial bone contouring and orthognathic surgery for the treatment of dentofacial deformities. Simultaneous facial bone contouring seems to be an alternative procedure in addition to conventional orthognathic surgery for cosmetic aims in certain patients. PMID- 27677686 TI - Application of Endodontic Files for the Extraction of Root Tips: A Biomechanical Investigation and Case Study. AB - PURPOSE: To investigate the appropriate endodontic file for the extraction of root tips through a biomechanical study and to evaluate the clinic efficiency of this technique. MATERIALS AND METHODS: Nine hundred molar roots were randomly divided into 3 groups (3, 5, and 7 mm) and amputated to the corresponding length. Different files were inserted into the root tips, and a pullout test was conducted using a universal testing machine. The pullout force was recorded and files with greatest pullout force were selected for clinical study. Patients' root tips were extracted using these files. The duration and incidence of postoperative complications were recorded. RESULTS: The greatest pullout force was obtained for the 25# Hedstrom file, regardless of the length of the root tip and the type of file. The pullout force of Hedstrom files was significantly greater than that of Kerr files in each file group and root length group (P < .05). Clinically, the direct success ratio of this technique was 81.4%. The incidence of postoperative complications was very low. CONCLUSION: The results of this study suggest that the application of endodontic files for the extraction of root tips is an acceptable technique. The 25# Hedstrom file is the optimum choice for root extraction in most cases when using endodontic files. PMID- 27677687 TI - Where genes meet environment-integrating the role of gut luminal contents, immunity and pancreas in type 1 diabetes. AB - The rise in new cases of type 1 diabetes (T1D) in genetically susceptible individuals over the past half century has been attributed to numerous environmental "triggers" or promoters such as enteroviruses, diet, and most recently, gut bacteria. No single cause has been identified in humans, likely because there are several pathways by which one can develop T1D. There is renewed attention to the role of the gut and its immune system in T1D pathogenesis based largely on recent animal studies demonstrating that altering the gut microbiota affects diabetes incidence. Although T1D patients display dysbiosis in the gut microbiome, it is unclear whether this is cause or effect. The heart of this question involves several moving parts including numerous risk genes, diet, viruses, gut microbiota, timing, and loss of immune tolerance to beta-cells. Most clinical trials have addressed only one aspect of this puzzle using some form of immune suppression, without much success. The key location where our genes meet and deal with the environment is the gastrointestinal tract. The influence of all of its major contents, including microbes, diet, and immune system, must be understood as part of the integrative biology of T1D before we can develop durable means of preventing, treating, or curing this disease. In the present review, we expand our previous gut-centric model based on recent developments in the field. PMID- 27677688 TI - ATRA Entrapped in DSPC Liposome Enhances Anti-metastasis Effect on Lung and Liver During B16F10 Cell Line Metastasis in C57BL6 Mice. AB - BACKGROUND: The high mortality rate of lung cancer is highly associated with faster metastasis spread. All Trans Retinoic Acid (ATRA), being the first choice drug for leukemia therapy is now under intense study for its therapeutic efficiency in other solid cancers. OBJECTIVES: This study was aimed to investigate the anti-metastasis activity of free ATRA and liposome entrapped ATRA (5:4:1) in the experimental C57BL/6 mice model developed by the injection of B16F10 cell line into the tail vein. METHOD: The ATRA drug was given via i.p for 21 days. The visual lung and liver metastatic tumor nodules were noted. Various biochemical markers of cancer metastasis in the serum as well as tissues were also analyzed after sacrifice. RESULTS: Tumor nodules have significantly decreased in ATRA treatment groups (32.83 +/- 1.83 for free ATRA, 23 +/- 2.36 for DSPC Lipo-ATRA) when compared with metastasis control (63.16 +/- 2.9) in the lungs. Among the treatment groups, the DSPC lipo-ATRA treated group showed a significant tumor growth inhibition (63.6%) than that of in the free ATRA treated groups (48%). Similar anti-metastatic effect was observed in liver also. Furthermore lipo-ATRA has shown a significant change in the levels of biochemical cancer markers analyzed in this study. CONCLUSION: Our results concluded that the liposome encapsulated ATRA has an enhanced anti-metastasis potency than the free ATRA during B16F10 metastatic cell line implantation. PMID- 27677689 TI - Bortezomib Enhances the Antitumor Effects of Interferon-beta Gene Transfer on Melanoma Cells. AB - BACKGROUND: Malignant melanoma is a fast growing form of skin cancer with increasing global incidence. Clinically, canine malignant melanoma and human melanoma share comparable treatment-resistances, metastatic phenotypes and site selectivity. OBJECTIVE: Both interferon-beta (IFNbeta) and bortezomib (BTZ) display inhibitory activities on melanoma cells. Here, we evaluated the cytotoxic effects of the combination of BTZ and IFNbeta gene lipofection on cultured melanoma cell lines. METHOD: Cell viability determined by the acid phosphatase method, cell migration mesasured by the wound healing assay, DNA fragmentation and cell cycle by flow cytometry after propidium iodide staining and reactive oxygen species (ROS) production by H2DCF-DA fluorescence. RESULTS: Four canine mucosal (Ak, Br, Bk and Ol) and two human dermal (A375 and SB2) melanoma cell lines were assayed. BTZ sub-pharmacological concentrations (5 nM) enhanced the cytotoxic effects of IFNbeta transgene expression on melanoma cells monolayers and spheroids. The combination was also more effective than the single treatments when assayed for clonogenic survival and cell migration. The combined treatment produced a significant raise of apoptosis evidenced by DNA fragmentation as compared to either BTZ or IFNbeta gene lipofection single treatments. Furthermore, BTZ significantly increased the intracellular ROS generation induced by IFNbeta gene transfer in melanoma cells, an effect that was reversed by the addition of the ROS inhibitor N-acetyl-L-cystein. CONCLUSION: The present work encourages further studies about the potential of the combination of interferon gene transfer with proteasome inhibitors as a new combined therapy for malignant melanoma, both in veterinary and/or human clinical settings. PMID- 27677690 TI - [Intraventricular hemorrhage after dural fistula embolization]. AB - BACKGROUND AND OBJECTIVES: Dural arteriovenous fistulas are anomalous shunts between dural arterial and venous channels whose nidus is located between the dural leaflets. For those circumstances when invasive treatment is mandatory, endovascular techniques have grown to become the mainstay of practice, choice attributable to their reported safety and effectiveness. We describe the unique and rare case of a dural arteriovenous fistula treated by transarterial embolization and complicated by an intraventricular hemorrhage. We aim to emphasize some central aspects of the perioperative management of these patients in order to help improving the future approach of similar cases. CASE REPORT: A 59-year-old woman with a previously diagnosed Cognard Type IV dural arteriovenous fistula presented for transarterial embolization, performed outside the operating room, under total intravenous anesthesia. The procedure underwent without complications and the intraoperative angiography revealed complete obliteration of the fistula. In the early postoperative period, the patient presented with clinical signs of raised intracranial pressure attributable to a later diagnosed intraventricular hemorrhage, which conditioned placement of a ventricular drain, admission to an intensive care unit, cerebral vasospasm and a prolonged hospital stay. Throughout the perioperative period, there were no changes in the cerebral brain oximetry. The patient was discharged without neurological sequelae. CONCLUSION: Intraventricular hemorrhage may be a serious complication after the endovascular treatment of dural arteriovenous fistula. A close postoperative surveillance and monitoring allow an early diagnosis and treatment which increases the odds for an improved outcome. PMID- 27677691 TI - Bone status assessed by quantitative ultrasound in children with inflammatory bowel disease: a comparison with DXA. AB - BACKGROUND: To determine the bone status in children with inflammatory bowel diseases (IBD) using quantitative ultrasound (QUS) measurement at hand phalanges and compare the obtained results with dual-energy X-ray absorptiometry (DXA). METHODS: Fifty-one children with IBD underwent DXA and QUS measurements at hand phalanges in the year 2013. The control group for the QUS consisted of 460 children. Reference data for DXA comes from Hologic Explorer. RESULTS: QUS measurements did not differ significantly between IBD patients and healthy controls. There was no difference between UC and CD subjects. DXA measurements in patients with IBD were lower than in the healthy population. Tanner stage and nutritional status correlated with bone status contrary to steroids therapy. CONCLUSION: Low bone mineral density often complicates IBD in children. QUS is not an appropriate method for the assessment of bone status in children. Nutritional status seems to have a greater impact on bone status than corticosteroids therapy. PMID- 27677692 TI - Predicting protein-protein interactions via multivariate mutual information of protein sequences. AB - BACKGROUND: Protein-protein interactions (PPIs) are central to a lot of biological processes. Many algorithms and methods have been developed to predict PPIs and protein interaction networks. However, the application of most existing methods is limited since they are difficult to compute and rely on a large number of homologous proteins and interaction marks of protein partners. In this paper, we propose a novel sequence-based approach with multivariate mutual information (MMI) of protein feature representation, for predicting PPIs via Random Forest (RF). METHODS: Our method constructs a 638-dimentional vector to represent each pair of proteins. First, we cluster twenty standard amino acids into seven function groups and transform protein sequences into encoding sequences. Then, we use a novel multivariate mutual information feature representation scheme, combined with normalized Moreau-Broto Autocorrelation, to extract features from protein sequence information. Finally, we feed the feature vectors into a Random Forest model to distinguish interaction pairs from non-interaction pairs. RESULTS: To evaluate the performance of our new method, we conduct several comprehensive tests for predicting PPIs. Experiments show that our method achieves better results than other outstanding methods for sequence-based PPIs prediction. Our method is applied to the S.cerevisiae PPIs dataset, and achieves 95.01 % accuracy and 92.67 % sensitivity repectively. For the H.pylori PPIs dataset, our method achieves 87.59 % accuracy and 86.81 % sensitivity respectively. In addition, we test our method on other three important PPIs networks: the one-core network, the multiple-core network, and the crossover network. CONCLUSIONS: Compared to the Conjoint Triad method, accuracies of our method are increased by 6.25,2.06 and 18.75 %, respectively. Our proposed method is a useful tool for future proteomics studies. PMID- 27677693 TI - Unexpected functional implication of a stable succinimide in the structural stability of Methanocaldococcus jannaschii glutaminase. AB - Protein ageing is often mediated by the formation of succinimide intermediates. These short-lived intermediates derive from asparaginyl deamidation and aspartyl dehydration and are rapidly converted into beta-aspartyl or D-aspartyl residues. Here we report the presence of a highly stable succinimide intermediate in the glutaminase subunit of GMP synthetase from the hyperthermophile Methanocaldoccocus jannaschii. By comparing the biophysical properties of the wild-type protein and of several mutants, we show that the presence of succinimide increases the structural stability of the glutaminase subunit. The protein bearing this modification in fact remains folded at 100 degrees C and in 8 M guanidinium chloride. Mutation of the residue following the reactive asparagine provides insight into the factors that contribute to the hydrolytic stability of the succinimide. Our findings suggest that sequences that stabilize succinimides from hydrolysis may be evolutionarily selected to confer extreme thermal stability. PMID- 27677694 TI - The acceptability of mass administrations of anti-malarial drugs as part of targeted malaria elimination in villages along the Thai-Myanmar border. AB - BACKGROUND: A targeted malaria elimination project, including mass drug administrations (MDA) of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations. METHODS: The household heads in four study villages in which MDAs had taken place previously were interviewed between January 2014 and July 2015. RESULTS: 174/378 respondents (46 %) completed three rounds of three drug doses each, 313/378 (83 %) took at least three consecutive doses and 56/378 (15 %) did not participate at all in the MDA. The respondents from the two villages (KNH and TPN) were much more likely to participate in the MDA than respondents from the other two villages (HKT and TOT). The more compliant villages KNH and TPN had both an appearance of cohesive communities with similar demographic and ethnic backgrounds. By contrast the villages with low participation were unique. One village was fragmented following years of armed conflict and many respondents gave little inclination to cooperate with outsiders. The other village with low MDA coverage was characterised by a high percentage of short-term residents with little interest in community interventions. A universal reason for non-participation in the MDA applicable to all villages was an inadequate understanding of the intervention. CONCLUSIONS: It is unlikely that community engagement can unite fragmented communities in participating in an intervention, which benefits the community. Understanding the purpose and the reasons underlying the intervention is an important pre-condition for participation. In the absence of direct benefits and a complete understanding of the indirect benefits trust in the investigators is critical for participation. PMID- 27677695 TI - Characterization of a neuropeptide F receptor in the tsetse fly, Glossina morsitans morsitans. AB - Neuropeptides related to mammalian neuropeptide Y (NPY) and insect neuropeptide F (NPF) are conserved throughout Metazoa and intimately involved in a wide range of biological processes. In insects NPF is involved in regulating feeding, learning, stress and reproductive behavior. Here we identified and characterized an NPF receptor of the tsetse fly, Glossina morsitans morsitans, the sole transmitter of Trypanosoma parasites causing sleeping sickness. We isolated cDNA sequences encoding tsetse NPF (Glomo-NPF) and its receptor (Glomo-NPFR), and examined their spatial and temporal expression patterns using quantitative PCR. In tsetse flies, npfr transcripts are expressed throughout development and most abundantly in the central nervous system, whereas low expression is found in the flight muscles and posterior midgut. Expression of npf, by contrast, shows low transcript levels during development but is strongly expressed in the posterior midgut and brain of adult flies. Expression of Glomo-npf and its receptor in the brain and digestive system suggests that NPF may have conserved neuromodulatory or hormonal functions in tsetse flies, such as in the regulation of feeding behavior. Cell-based activity studies of the Glomo-NPFR showed that Glomo-NPF activates the receptor up to nanomolar concentrations. The molecular data of Glomo-NPF and Glomo-NPFR paves the way for further investigation of its functions in tsetse flies. PMID- 27677696 TI - Sexual variation of bacterial microbiota of Dendroctonus valens guts and frass in relation to verbenone production. AB - Gut microbiota are widely involved in insect biology, and many factors can influence the microbiota in guts and frass. Dendroctonus valens is a very destructive forest pest in China, and the mass-attacking behavior is regulated by several semiochemicals, including verbenone, a multifunctional pheromone. The beetle harbors a variety of bacteria in its guts and frass and some of them are capable of verbenone production. D. valens is characterized by monogamy and female-initiated attacking behavior. Whether the bacterial communities fluctuate according to sex, and whether the variation influences the verbenone production, remains to be determined. In this study, the bacterial microbiota in D. valens guts and frass were analyzed, and verbenone production by their crude bacterial suspensions was compared in vitro. Bacterial diversity in female frass is more abundant compared to male frass, and the percentages and total amounts of main genera like Lactococcus and Pseudomonas in female frass are significantly higher than those in male frass. The verbenone produced by the female frass suspension is significantly higher than male frass. This study presents a comprehensive comparison of bacterial communities in guts and frass between both sexes of D. valens, highlighting the potential significance of female frass microbiota in verbenone production. PMID- 27677698 TI - Role of assessing liver fibrosis in management of chronic hepatitis C virus infection. AB - Fibrosis progression is common in hepatitis C. Both host and viral factors influence its natural history. Liver fibrosis is a key predictive factor for advanced disease including endpoints such as liver failure, cirrhosis and hepatocellular carcinoma (HCC). METAVIR fibrosis stages F3-F4 have been considered as the threshold for antiviral therapy. However, this aspect is controversial after the advent of new direct-acting antivirals (DAAs) because they show an excellent efficacy and safety profile. Moreover, in the DAA era, fibrosis stage seems not to be a predictive factor of a sustained virological response (SVR). Viral eradication decreases liver damage by improving the inflammation, as well as by regressing fibrosis irrespective of the treatment regimen. Non-invasive methods are useful in the assessment of liver fibrosis, replacing liver biopsy in clinical practice; but their usefulness for monitoring fibrosis after SVR needs to be demonstrated. Fibrosis regression has been demonstrated after the eradication of hepatitis C virus infection and is associated with a lower risk of hepatic cirrhosis and liver cancer. However, patients showing advanced fibrosis and cirrhosis must be followed-up after SVR, as risks of portal hypertension and HCC remain. PMID- 27677699 TI - Usutu virus infections in humans: a retrospective analysis in the municipality of Modena, Italy. AB - OBJECTIVE: To monitor the spread and to evaluate the role for public health of Usutu virus (USUV) in an endemic area of Italy. METHODS: The survey was retrospectively conducted by detecting USUV RNA and USUV antibodies in cerebrospinal fluid and serum samples collected between 2008 and 2011 from 915 patients with or without neurologic impairments in the area of the municipality of Modena, Italy. Organs of birds and pools of mosquitoes were also tested for USUV RNA. Positive samples were partially sequenced and used for phylogenetic analysis. RESULTS: The presence of USUV RNA (1.1%; 95% confidence interval (CI) 0.6-2.0) was significantly (p <0.05) higher than that of West Nile virus (0%; 95% CI 0-0.33). USUV antibody level was 6.57% (95% CI 4.87-8.82), and it was significantly higher (p <0.05) compared to that of West Nile virus (p 2.96, 95% CI 1.89-4.62). Partial genome sequencing of USUV strains detected in humans, birds and mosquitoes revealed high nucleotide sequence identity within them and with the USUV strains isolated in Central Europe. CONCLUSIONS: USUV infection in humans is not a sporadic event in the studied area, and USUV neuroinvasiveness has been confirmed. PMID- 27677697 TI - Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia. AB - OBJECTIVE: Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG. METHODS: We analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results with clinical outcome of the patients. RESULTS: Around 70% (484/690) of the isolates exhibited TE to azoles. Candida tropicalis showed the highest presence of TE (39/53 isolates exhibited residual growth >25% of control). No TE was seen in most of the isolates from the psilosis complex. PG was mainly associated with echinocandins. In patients treated with fluconazole within the first 48 hours after blood sampling (n = 221), the presence of TE to azoles tended to be associated with lower 30-day mortality (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25-1.00) but not with clinical failure (OR 0.85, 95% CI 0.45 1.54). In the subgroup of 117 patients treated with echinocandins, the presence of PG was not associated with patient's response to antifungal treatment (OR for 30-day mortality 1.63, 95% CI 0.76-4.03; OR for clinical failure 1.17, 95% CI 0.53-2.70). CONCLUSIONS: TE or PG are widely expressed among Candida spp., although they do not seem to influence clinical outcome. PMID- 27677701 TI - Proceedings of the IX International Symposium on Phlebotomine Sandflies (ISOPS IX), Reims, France, June 28th-July 1st, 2016. PMID- 27677700 TI - Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts. AB - BACKGROUND: Systemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112rGEMCI20 in vitro and in vivo. METHODS: RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112rGEMCI20) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. RESULTS: Dasatinib exerted similar effects on Src signaling in RT112 and RT112rGEMCI20 cells but RT112rGEMCI20 cells were less sensitive to dasatinib induced anti-cancer effects (half maximal inhibitory concentration (IC50) of dasatinib in RT112 cells: 349.2 +/- 67.2 nM; IC50 of dasatinib in RT112rGEMCI20 cells: 1081.1 +/- 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112rGEMCI20 tumors. CONCLUSION: Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases. PMID- 27677702 TI - The correlation between cognitive performance and retinal nerve fibre layer thickness is largely explained by genetic factors. AB - Retinal nerve fibre layer (RNFL) thickness has been associated with cognitive function but it is unclear whether RNFL thinning is secondary to cortical loss, or if the same disease process affects both. We explored whether there is phenotypic sharing between RNFL thickness and cognitive traits, and whether such sharing is due to genetic factors. Detailed eye and cognitive examination were performed on 1602 twins (mean age: 56.4 years; range: 18-89) from the TwinsUK cohort. Associations between RNFL thickness and ophthalmic, cognitive and other predictors were assessed using linear regression or analysis of variance models. Heritability analyses were performed using uni- and bivariate Cholesky decomposition models. RNFL was thinner with increase in myopia and with decrease in disc area (p < 0.001). A thicker RNFL was associated with better performance on mini mental state examination (MMSE, F(5,883) = 5.8, p < 0.001), and with faster reaction time (RT, beta = -0.01; p = 0.01); independent of the effects of age, refractive error and disc area (p < 0.05). RNFL thickness was highly heritable (82%) but there was low phenotypic sharing between RNFL thickness and MMSE (5%, 95% CI: 0-10%) or RT (7%, 95% CI: 1-12%). This sharing, however, was mostly due to additive genetic effects (67% and 92% of the shared variance respectively). PMID- 27677703 TI - Loss of Schwann cell plasticity in chronic inflammatory demyelinating polyneuropathy (CIDP). AB - BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is often associated with chronic disability, which can be accounted to incomplete regeneration of injured axons. We hypothesized that Schwann cell support for regenerating axons may be altered in CIDP, which may account for the poor clinical recovery seen in many patients. METHODS: We exposed human and rodent Schwann cells to sera from CIDP patients and controls. In a model of chronic nerve denervation, we transplanted these conditioned Schwann cells intraneurally and assessed their capacity to support axonal regeneration by electrophysiology and morphometry. RESULTS: CIDP-conditioned Schwann cells were less growth supportive for regenerating axons as compared to Schwann cells exposed to control sera. The loss of Schwann cell support was associated with lower levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in CIDP sera and correlated with altered expression of c-Jun and p57kip2 in Schwann cells. The inactivation of these regulatory factors resulted in an altered expression of neurotrophins including BDNF, GDNF, and NGF in CIDP-conditioned Schwann cells in vitro. CONCLUSIONS: Our study provides evidence that pro-regenerative functions of Schwann cells are affected in CIDP. It thereby offers a possible explanation for the clinical observation that in many CIDP patients recovery is incomplete despite sufficient immunosuppressive treatment. PMID- 27677705 TI - Use of a least absolute shrinkage and selection operator (LASSO) model to selected ion flow tube mass spectrometry (SIFT-MS) analysis of exhaled breath to predict the efficacy of dialysis: a pilot study. AB - Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a full-mass scan of volatile compounds in exhaled breath. Although various studies have suggested that breath metabolites may be indicators of human disease status, many of these studies have included few breath samples and large numbers of compounds, limiting their power to detect significant metabolites. This study employed a least absolute shrinkage and selective operator (LASSO) approach to SIFT-MS data of breath samples to preliminarily evaluate the ability of exhaled breath findings to monitor the efficacy of dialysis in hemodialysis patients. A process of model building and validation showed that blood creatinine and urea concentrations could be accurately predicted by LASSO-selected masses. Using various precursors, the LASSO models were able to predict creatinine and urea concentrations with high adjusted R square (>80%) values. The correlation between actual concentrations and concentrations predicted by the LASSO model (using precursor H3O+) was high (Pearson correlation coefficient = 0.96). Moreover, use of full mass scan data provided a better prediction than compounds from selected ion mode. These findings warrant further investigations in larger patient cohorts. By employing a more powerful statistical approach to predict disease outcomes, breath analysis using SIFT-MS technology could be applicable in future to daily medical diagnoses. PMID- 27677704 TI - Embryonic expression of endothelins and their receptors in lamprey and frog reveals stem vertebrate origins of complex Endothelin signaling. AB - Neural crest cells (NCCs) are highly patterned embryonic cells that migrate along stereotyped routes to give rise to a diverse array of adult tissues and cell types. Modern NCCs are thought to have evolved from migratory neural precursors with limited developmental potential and patterning. How this occurred is poorly understood. Endothelin signaling regulates several aspects of NCC development, including their migration, differentiation, and patterning. In jawed vertebrates, Endothelin signaling involves multiple functionally distinct ligands (Edns) and receptors (Ednrs) expressed in various NCC subpopulations. To test the potential role of endothelin signaling diversification in the evolution of modern, highly patterned NCC, we analyzed the expression of the complete set of endothelin ligands and receptors in the jawless vertebrate, the sea lamprey (Petromyzon marinus). To better understand ancestral features of gnathostome edn and ednr expression, we also analyzed all known Endothelin signaling components in the African clawed frog (Xenopus laevis). We found that the sea lamprey has a gnathsotome-like complement of edn and ednr duplicates, and these genes are expressed in patterns highly reminiscent of their gnathostome counterparts. Our results suggest that the duplication and specialization of vertebrate Endothelin signaling coincided with the appearance of highly patterned and multipotent NCCs in stem vertebrates. PMID- 27677706 TI - Rolling behavior of a micro-cylinder in adhesional contact. AB - Understanding the rolling behavior of a micro-object is essential to establish the techniques of micro-manipulation and micro-assembly by mechanical means. Using a combined theoretical/computational approach, we studied the critical conditions of rolling resistance of an elastic cylindrical micro-object in adhesional contact with a rigid surface. Closed-form dimensionless expressions for the critical rolling moment, the initial rolling contact area, and the initial rolling angle were extracted after a systematic parametric study using finite element method (FEM) simulations. The total energy of this system is defined as the sum of three terms: the elastic energy stored in the deformed micro-cylinder, the interfacial energy within the contact area, and the mechanical potential energy that depends on the external moment applied to the cylindrical micro-object. A careful examination of the energy balance of the system surprisingly revealed that the rolling resistance per unit cylindrical length can be simply expressed by "work of adhesion times cylindrical radius" independent of the Young's modulus. In addition, extending a linear elastic fracture mechanics based approach in the literature, we obtained the exact closed form asymptotic solutions for the critical conditions for initial rolling; these asymptotic solutions were found in excellent agreement with the full-field FEM results. PMID- 27677707 TI - Total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer: Comparative analysis after propensity score matching: A multicenter study. AB - BACKGROUND: In patients with papillary thyroid carcinoma (PTC), the role of total thyroidectomy (TT) versus that of thyroid lobectomy (TL) has been controversial. METHODS: This retrospective study was approved by our institutional review board, and the requirement to obtain informed consent was waived. In total, 173 patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by curative surgery from 1994 to 2008 were evaluated. Clinicopathologic features and adverse events were compared between patients who underwent TT and those who underwent TL. After adjustment for differences in baseline clinicopathologic factors using propensity score matching, we compared recurrence-free survival (RFS) and OS. RESULTS: TL was performed in 120 patients and TT in 53 patients. Patients who underwent TT were older; had larger tumors; more frequently had nodal metastasis, multifocal tumors, and extracapsular invasion; and more frequently underwent radioactive iodine ablation than patients who underwent TL. Hypocalcemia requiring medication and recurrent laryngeal nerve paralysis were more frequent in TT than TL. The 10 year RFS and OS of all patients were 93.3% and 96.7%, respectively. There was no significant difference in RFS (90.6% vs 93.0% in TT and TL groups, respectively) or OS (96.2% vs 96.9% in TT and TL groups, respectively) according to the extent of surgical resection after propensity score matching. CONCLUSION: Equivalent prognoses were observed for patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by TL or TT after propensity score matching. Adverse events occurred less frequently in patients who underwent TL than TT. PMID- 27677708 TI - Improving protein content and quality by over-expressing artificially synthetic fusion proteins with high lysine and threonine constituent in rice plants. AB - Rice grains are rich in starch but low in protein with very low level of both lysine and threonine. Thus, it is important to further improve protein quality and quantity, especially to increase lysine and threonine content in rice grains. We artificially synthesized two new genes by fusing endogenous rice genes with lysine (K)/threonine (T) motif (TKTKK) coding sequences. They were designated as TKTKK1 and TKTKK2 and their encoded proteins consist of 73.1% and 83.5% of lysine/threonine, respectively. These two genes were under the control of 35S promoter and were independently introduced into the rice genome to generate transgenic plants. Our data showed that overexpression of TKTKK1 generated stable proteins with expected molecular weight and the transgenic rice seeds significantly increased lysine, threonine, total amino acids and crude protein content by 33.87%, 21.21%, 19.43% and 20.45%, respectively when compared with wild type control; significant improvement was also observed in transgenic rice seeds overexpressing TKTKK2. However, limited improvement in protein quality and quantity was observed in transgenic seeds carrying tandom array of these two new genes. Our data provide the basis and alternative strategy on further improving protein quality and quantity in other crops or vegetable plants by synthetic biology. PMID- 27677710 TI - Optically Transparent Ferromagnetic Nanogranular Films with Tunable Transmittance. AB - Developing optically transparent magnets at room temperature is an important challenge. They would bring many innovations to various industries, not only for electronic and magnetic devices but also for optical applications. Here we introduce FeCo-(Al-fluoride) nanogranular films exhibiting ferromagnetic properties with high optical transparency in the visible light region. These films have a nanocomposite structure, in which nanometer-sized FeCo ferromagnetic granules are dispersed in an Al-fluoride crystallized matrix. The optical transmittance of these films is controlled by changing the magnetization. This is a new type of magneto-optical effect and is explained by spin-dependent charge oscillation between ferromagnetic granules due to quantum-mechanical tunneling. PMID- 27677709 TI - Stress hyperglycaemia in critically ill patients and the subsequent risk of diabetes: a systematic review and meta-analysis. AB - BACKGROUND: Hyperglycaemia occurs frequently in critically ill patients without diabetes. We conducted a systematic review and meta-analysis to evaluate whether this 'stress hyperglycaemia' identifies survivors of critical illness at increased risk of subsequently developing diabetes. METHODS: We searched the MEDLINE and Embase databases from their inception to February 2016. We included observational studies evaluating adults admitted to the intensive care unit (ICU) who developed stress hyperglycaemia if the researchers reported incident diabetes or prediabetes diagnosed >=3 months after hospital discharge. Two reviewers independently screened the titles and abstracts of identified studies and evaluated the full text of relevant studies. Data were extracted using pre defined data fields, and risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled ORs with 95 % CIs for the occurrence of diabetes were calculated using a random-effects model. RESULTS: Four cohort studies provided 2923 participants, including 698 with stress hyperglycaemia and 131 cases of newly diagnosed diabetes. Stress hyperglycaemia was associated with increased risk of incident diabetes (OR 3.48; 95 % CI 2.02-5.98; I 2 = 36.5 %). Studies differed with regard to definitions of stress hyperglycaemia, follow-up and cohorts studied. CONCLUSIONS: Stress hyperglycaemia during ICU admission is associated with increased risk of incident diabetes. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies. PMID- 27677711 TI - Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. AB - Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ~50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy. PMID- 27677712 TI - Personalized treatment of patients with very early hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC), in its very early stage, is heterogeneous both in terms of liver function (i.e., presence or absence of portal hypertension, model for end-stage liver disease score, Child-Pugh score 5 or 6, bilirubin level) and tumor characteristics (i.e., location, alpha-fetoprotein values, pathological features such as microvascular invasion, tumor grade and satellitosis). Existing evidence in comparing different curative options for patients with very early HCC is poor due to small sample sizes and lack of solid subgroup analyses. Large observational studies are available, with the potential to identify effective interventions in different subgroup of patients and to discover which treatments work "in a real world setting". These studies suggest some important treatment selection strategies in very early HCC patients. According to extent of liver resection, and liver function, percutaneous ablation or liver resection are the recommended first line therapies in these patients. Laparoscopic surgery (resection or ablation) is the preferable strategy when the tumor is in the surface of the liver or close to extra-hepatic organs. Due to scarce donor resources and competition with patients at high transplant benefit (HCC patients unsuitable for non-transplant radical therapies and non-HCC patients with decompensated cirrhosis), transplantation is recommended only as second line therapy in patients with very early stage HCC in case of tumor recurrence or liver failure after ablation or liver resection. PMID- 27677713 TI - A rare and revealing glimpse of the cerebrospinal fluid of patients with hepatic encephalopathy. PMID- 27677714 TI - The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma. AB - BACKGROUND & AIMS: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS: We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS: Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS: In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY: Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC. PMID- 27677716 TI - Is Persistent Office Hypertension in Treated Hypertensive Patients a Benign Condition? PMID- 27677715 TI - Molecular basis of the interaction between gating modifier spider toxins and the voltage sensor of voltage-gated ion channels. AB - Voltage-sensor domains (VSDs) are modular transmembrane domains of voltage-gated ion channels that respond to changes in membrane potential by undergoing conformational changes that are coupled to gating of the ion-conducting pore. Most spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state. To understand the molecular basis underlying this mode of action, we used nuclear magnetic resonance to delineate the atomic details of the interaction between the VSD of the voltage-gated potassium channel KvAP and the spider-venom peptide VSTx1. Our data reveal that the toxin interacts with residues in an aqueous cleft formed between the extracellular S1-S2 and S3-S4 loops of the VSD whilst maintaining lipid interactions in the gaps formed between the S1-S4 and S2-S3 helices. The resulting network of interactions increases the energetic barrier to the conformational changes required for channel gating, and we propose that this is the mechanism by which gating modifier toxins inhibit voltage-gated ion channels. PMID- 27677717 TI - Liver cancer: IGF2 - an epigenetic oncodriver in HCC. PMID- 27677718 TI - Human mini-guts: new insights into intestinal physiology and host-pathogen interactions. AB - The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5+ intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions. PMID- 27677721 TI - Proteinases, Their Extracellular Targets, and Inflammatory Signaling. AB - Given that over 2% of the human genome codes for proteolytic enzymes and their inhibitors, it is not surprising that proteinases serve many physiologic pathophysiological roles. In this context, we provide an overview of proteolytic mechanisms regulating inflammation, with a focus on cell signaling stimulated by the generation of inflammatory peptides; activation of the proteinase-activated receptor (PAR) family of G protein-coupled receptors (GPCR), with a mechanism in common with adhesion-triggered GPCRs (ADGRs); and by proteolytic ion channel regulation. These mechanisms are considered in the much wider context that proteolytic mechanisms serve, including the processing of growth factors and their receptors, the regulation of matrix-integrin signaling, and the generation and release of membrane-tethered receptor ligands. These signaling mechanisms are relevant for inflammatory, neurodegenerative, and cardiovascular diseases as well as for cancer. We propose that the inflammation-triggering proteinases and their proteolytically generated substrates represent attractive therapeutic targets and we discuss appropriate targeting strategies. PMID- 27677727 TI - Neuropsychological performance and seizure control after subsequent anteromesial temporal lobe resection following selective amygdalohippocampectomy. AB - OBJECTIVE: Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). METHODS: Patients' characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. RESULTS: Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. SIGNIFICANCE: Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline. PMID- 27677728 TI - Associations of Postdiagnosis Physical Activity and Change from Prediagnosis Physical Activity with Quality of Life in Prostate Cancer Survivors. AB - BACKGROUND: This prospective study examined the associations between postdiagnosis physical activity and change from prediagnosis physical activity with quality of life (QoL) in prostate cancer survivors. METHODS: Prostate cancer survivors (N = 830) who participated in a case-control study with invasive stage >=II disease were followed up to 2007 to capture QoL outcomes. At baseline and three time points postdiagnosis (2000-2007), interviews/questionnaires were used to collect data on physical activity, general QoL measured by the SF-36, and other treatment/lifestyle factors. Multivariable linear regression was used to test the relation between postdiagnosis physical activity and QoL as well as the change in physical activity over the diagnostic period and QoL. RESULTS: Both total and recreational physical activities were positively associated with physical QoL. Furthermore, when comparing changes in physical activity levels from pre- to postdiagnosis, men who consistently met physical activity guidelines had significantly higher physical [beta = 6.01; 95% confidence interval (CI), 4.15-7.86] and mental (beta = 2.32; 95% CI, 0.29-4.34) QoL scores compared with those who did not meet guidelines pre- or postdiagnosis. Furthermore, those who adopted and met guidelines had increased QoL, whereas those who relapsed experienced decreased QoL. CONCLUSIONS: Postdiagnosis recreational physical activity is associated with better physical QoL in prostate cancer survivors. Moreover, prostate cancer survivors who maintain or adopt physical activity after diagnosis report substantially higher QoL than men who never exercised or stopped exercising after diagnosis. IMPACT: Future intervention studies should focus on achieving and maintaining adherence to physical activity guidelines postdiagnosis in prostate cancer survivors. Cancer Epidemiol Biomarkers Prev; 26(2); 179-87. (c)2016 AACR. PMID- 27677729 TI - Telomere Length and Breast Cancer Prognosis: A Systematic Review. AB - Telomeres ensure genome integrity during replication. Loss of telomeric function leads to cell immortalization and accumulation of genetic alterations. The association of telomere length (TL) with breast cancer prognosis is examined through a systematic review. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2015, and relevant reviews were searched. Studies that evaluated TL (blood and/or tumor) in association with breast cancer survival or prognostic factor were included. Thirty-six studies met inclusion criteria. Overall risk of bias was critical. Eight studies reported survival outcomes. Overall, there was a trend toward an association of longer telomeres with better outcomes (tumor, not blood). Of the 33 studies reporting associations with prognostic factors, nine adjusted for potential confounders. Among the latter, shorter telomeres were associated with older age (blood, not tumor), higher local recurrence rates (normal tissue), higher tumor grade (tumor), and lower physical activity (blood), which were reported in one study each. TL was not associated with molecular subtype (blood, one study), family history (tumor, one study), chemotherapy (blood, three of four studies), and stress reduction interventions (blood, two of two studies). Although major methodologic differences preclude from drawing conclusive results, TL could be a valuable breast cancer prognostic marker. Cancer Epidemiol Biomarkers Prev; 26(1); 3-10. (c)2016 AACR. PMID- 27677731 TI - Do Narcissism and Emotional Intelligence Win Us Friends? Modeling Dynamics of Peer Popularity Using Inferential Network Analysis. AB - This research investigated effects of narcissism and emotional intelligence (EI) on popularity in social networks. In a longitudinal field study, we examined the dynamics of popularity in 15 peer groups in two waves ( N = 273). We measured narcissism, ability EI, and explicit and implicit self-esteem. In addition, we measured popularity at zero acquaintance and 3 months later. We analyzed the data using inferential network analysis (temporal exponential random graph modeling, TERGM) accounting for self-organizing network forces. People high in narcissism were popular, but increased less in popularity over time than people lower in narcissism. In contrast, emotionally intelligent people increased more in popularity over time than less emotionally intelligent people. The effects held when we controlled for explicit and implicit self-esteem. These results suggest that narcissism is rather disadvantageous and that EI is rather advantageous for long-term popularity. PMID- 27677720 TI - Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior. AB - Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative-motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence. PMID- 27677734 TI - Self-Assembled Materials Made from Functional Recombinant Proteins. AB - Proteins are potent molecules that can be used as therapeutics, sensors, and biocatalysts with many advantages over small-molecule counterparts due to the specificity of their activity based on their amino acid sequence and folded three dimensional structure. However, they also have significant limitations in their stability, localization, and recovery when used in soluble form. These opportunities and challenges have motivated the creation of materials from such functional proteins in order to protect and present them in a way that enhances their function. We have designed functional recombinant fusion proteins capable of self-assembling into materials with unique structures that maintain or improve the functionality of the protein. Fusion of either a functional protein or an assembly domain to a leucine zipper domain makes the materials design strategy modular, based on the high affinity between leucine zippers. The self-assembly domains, including elastin-like polypeptides (ELPs) and defined-sequence random coil polypeptides, can be fused with a leucine zipper motif in order to promote assembly of the fusion proteins into larger structures upon specific stimuli such as temperature and ionic strength. Fusion of other functional domains with the counterpart leucine zipper motif endows the self-assembled materials with protein specific functions such as fluorescence or catalytic activity. In this Account, we describe several examples of materials assembled from functional fusion proteins as well as the structural characterization, functionality, and understanding of the assembly mechanism. The first example is zipper fusion proteins containing ELPs that assemble into particles when introduced to a model extracellular matrix and subsequently disassemble over time to release the functional protein for drug delivery applications. Under different conditions, the same fusion proteins can self-assemble into hollow vesicles. The vesicles display a functional protein on the surface and can also carry protein, small molecule, or nanoparticle cargo in the vesicle lumen. To create a material with a more complex hierarchical structure, we combined calcium phosphate with zipper fusion proteins containing random coil polypeptides to produce hybrid protein inorganic supraparticles with high surface area and porous structure. The use of a functional enzyme created supraparticles with the ability to degrade inflammatory cytokines. Our characterization of these protein materials revealed that the molecular interactions are complex because of the large size of the protein building blocks, their folded structures, and the number of potential interactions including hydrophobic interactions, electrostatic interactions, van der Waals forces, and specific affinity-based interactions. It is difficult or even impossible to predict the structures a priori. However, once the basic assembly principles are understood, there is opportunity to tune the material properties, such as size, through control of the self-assembly conditions. Our future efforts on the fundamental side will focus on identifying the phase space of self-assembly of these fusion proteins and additional experimental levers with which to control and tune the resulting materials. On the application side, we are investigating an array of different functional proteins to expand the use of these structures in both therapeutic protein delivery and biocatalysis. PMID- 27677732 TI - Clinical Pharmacokinetics of Mycophenolic Acid in Hematopoietic Stem Cell Transplantation Recipients. AB - Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is widely used as a maintenance immunosuppressive regimen in solid organ transplant patients. It is increasingly used for the prophylaxis and treatment of graft versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT) patients. MPA displays extensive binding to serum albumin and glucuronidation to the inactive MPA-7-O-glucuronide (MPAG). Here, we review and discuss the pertinent information regarding the clinical pharmacokinetics of MPA in HSCT patients. The pharmacokinetics of MPA are altered in HSCT patients with lower oral bioavailability, shorter half-life and higher clearance than those in healthy volunteers and renal transplant recipients. Moreover, clearance may be increased in young pediatric patients. The optimal MMF dosing and preferred targets are still under investigation in HSCT patients due to the substantial intra- and inter-individual pharmacokinetic variability of MPA and broad range of transplants (malignant vs. nonmalignant, related vs. unrelated donor, and human leukocyte antigen mismatch). The complex pharmacokinetics of MPA have partly hampered the efficient use of MMF, and pharmacokinetic studies in HSCT patients have been limited in size and mostly inconclusive. Future research should be multi-institutional and focus on developing clinical decisions with adequate statistical power to improve clinical care of HSCT recipients. PMID- 27677733 TI - Kinematic Visual Biofeedback Improves Accuracy of Learning a Swallowing Maneuver and Accuracy of Clinician Cues During Training. AB - Submental surface electromyography (ssEMG) visual biofeedback is widely used to train swallowing maneuvers. This study compares the effect of ssEMG and videofluoroscopy (VF) visual biofeedback on hyo-laryngeal accuracy when training a swallowing maneuver. Furthermore, it examines the clinician's ability to provide accurate verbal cues during swallowing maneuver training. Thirty healthy adults performed the volitional laryngeal vestibule closure maneuver (vLVC), which involves swallowing and sustaining closure of the laryngeal vestibule for 2 s. The study included two stages: (1) first accurate demonstration of the vLVC maneuver, followed by (2) training-20 vLVC training swallows. Participants were randomized into three groups: (a) ssEMG biofeedback only, (b) VF biofeedback only, and (c) mixed biofeedback (VF for the first accurate demonstration achieving stage and ssEMG for the training stage). Participants' performances were verbally critiqued or reinforced in real time while both the clinician and participant were observing the assigned visual biofeedback. VF and ssEMG were continuously recorded for all participants. Results show that accuracy of both vLVC performance and clinician cues was greater with VF biofeedback than with either ssEMG or mixed biofeedback (p < 0.001). Using ssEMG for providing real time biofeedback during training could lead to errors while learning and training a swallowing maneuver. PMID- 27677736 TI - Novel benzothiophene 1,1-dioxide deoxygenation path for the microwave-assisted synthesis of substituted benzothiophene-fused pyrrole derivatives. AB - The reaction of C-(4-substituted-phenyl)-N-(benzoyl)-N-methylglycines with benzo[b]thiophene 1,1-dioxide unexpectedly gave benzothiophene-fused pyrrole derivatives in toluene under microwave irradiation via a cycloaddition and metal free Pummerer-type sulfone deoxygenation path. In order to obtain the desired sulfone derivatives, the sulfide group underwent oxidation with m-CPBA to afford sulfones. The structures of all the new products were elucidated by spectroscopic/physical methods and, in two cases, by X-ray diffraction. PMID- 27677730 TI - No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival. AB - Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses.Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival.Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 * 10-5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival.Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes.Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. (c)2016 AACR. PMID- 27677735 TI - Antioxidative and antiproliferative activities of novel pyrido[1,2 a]benzimidazoles. AB - A series of pyrido[1,2-a]benzimidazoles has been designed, and novel examples are synthesized and evaluated for their potential antiproliferative activity against four human tumour cell lines-cervical (HeLa), colorectal (SW620), breast (MCF-7) and hepatocellular carcinoma (HepG2). In addition, their antioxidative potency has been evaluated by in vitro spectrophotometric assays. Preliminary structure activity relationships among the synthesized compounds are discussed. Evaluation of their antioxidative capacity has shown that two compounds (25 and 26) possess promising reducing characteristics and free radical scavenging activity. Selective antiproliferative effect in the single-digit micromolar range was observed for compound 25 on MCF-7 [Formula: see text] and HeLa [Formula: see text] cell lines, comparable to the standards 5-fluorouracil and cisplatin. The combination of the radical scavenging activity and antiproliferative activity of compound 25 positions this compound as a potential lead candidate for further optimization. PMID- 27677719 TI - Botanicals and Their Bioactive Phytochemicals for Women's Health. AB - Botanical dietary supplements are increasingly popular for women's health, particularly for older women. The specific botanicals women take vary as a function of age. Younger women will use botanicals for urinary tract infections, especially Vaccinium macrocarpon (cranberry), where there is evidence for efficacy. Botanical dietary supplements for premenstrual syndrome (PMS) are less commonly used, and rigorous clinical trials have not been done. Some examples include Vitex agnus-castus (chasteberry), Angelica sinensis (dong quai), Viburnum opulus/prunifolium (cramp bark and black haw), and Zingiber officinale (ginger). Pregnant women have also used ginger for relief from nausea. Natural galactagogues for lactating women include Trigonella foenum-graecum (fenugreek) and Silybum marianum (milk thistle); however, rigorous safety and efficacy studies are lacking. Older women suffering menopausal symptoms are increasingly likely to use botanicals, especially since the Women's Health Initiative showed an increased risk for breast cancer associated with traditional hormone therapy. Serotonergic mechanisms similar to antidepressants have been proposed for Actaea/Cimicifuga racemosa (black cohosh) and Valeriana officinalis (valerian). Plant extracts with estrogenic activities for menopausal symptom relief include Glycine max (soy), Trifolium pratense (red clover), Pueraria lobata (kudzu), Humulus lupulus (hops), Glycyrrhiza species (licorice), Rheum rhaponticum (rhubarb), Vitex agnus-castus (chasteberry), Linum usitatissimum (flaxseed), Epimedium species (herba Epimedii, horny goat weed), and Medicago sativa (alfalfa). Some of the estrogenic botanicals have also been shown to have protective effects against osteoporosis. Several of these botanicals could have additional breast cancer preventive effects linked to hormonal, chemical, inflammatory, and/or epigenetic pathways. Finally, although botanicals are perceived as natural safe remedies, it is important for women and their healthcare providers to realize that they have not been rigorously tested for potential toxic effects and/or drug/botanical interactions. Understanding the mechanism of action of these supplements used for women's health will ultimately lead to standardized botanical products with higher efficacy, safety, and chemopreventive properties. PMID- 27677738 TI - Synthesis of amino ester-embedded benzimidazoles: a one-pot sequential protocol under metal-free neutral conditions. AB - A one-pot three-component protocol has been developed for the synthesis of amino ester-embedded benzimidazoles under metal-free neutral conditions. Sequentially, the methodology involves coupling of an amino ester with 1-fluoro-2-nitrobenzene, reduction of the coupled nitroarene by sodium dithionite, and cyclization of the corresponding diamine with an aldehyde. PMID- 27677737 TI - A versatile strategy for the design and synthesis of novel ADP conjugates and their evaluation as potential poly(ADP-ribose) polymerase 1 inhibitors. AB - A versatile strategy for the synthesis of [Formula: see text] mimetics was developed, involving an efficient pyrophosphate linkage formation in key conjugates containing a functional amino group which acts as useful reactive anchor for further derivatization. These [Formula: see text] mimetics consist of ADP conjugated through a diphosphate chain to an extended aliphatic linker bearing an aromatic acid residue. A number of conjugates containing aromatic carboxylic acids were found to inhibit poly(ADP-ribose) synthesis catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1). A new class of potential PARP-1 inhibitors mimicking [Formula: see text], a substrate in the PARP-1 catalyzed reaction, was proposed. PMID- 27677739 TI - Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms. PMID- 27677740 TI - BET protein bromodomain inhibitor-based combinations are highly active against post-myeloproliferative neoplasm secondary AML cells. AB - Myeloproliferative neoplasms with myelofibrosis (MPN-MF) demonstrate constitutive activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling that responds to treatment with the JAK1 and 2 kinase inhibitor (JAKi) ruxolitinib. However, MPN-MF often progresses (~20%) to secondary acute myeloid leukemia (sAML), where standard induction chemotherapy or ruxolitinib is relatively ineffective, necessitating the development of novel therapeutic approaches. In the present studies, we demonstrate that treatment with BET (bromodomain and extraterminal) protein inhibitor (BETi), for example, JQ1, inhibits growth and induces apoptosis of cultured and primary, patient derived (PD), post-MPN sAML blast progenitor cells. Reverse-phase protein array, mass-cytometry and Western analyses revealed that BETi treatment attenuated the protein expressions of c-MYC, p-STAT5, Bcl-xL, CDK4/6, PIM1 and IL-7R, whereas it concomitantly induced the levels of HEXIM1, p21 and BIM in the sAML cells. Co treatment with BETi and ruxolitinib synergistically induced apoptosis of cultured and PD sAML cells, as well as significantly improved survival of immune-depleted mice engrafted with human sAML cells. Although BETi or heat shock protein 90 inhibitor (HSP90i) alone exerted lethal activity, cotreatment with BETi and HSP90i was synergistically lethal against the ruxolitinib-persister or ruxolitinib-resistant sAML cells. Collectively, these findings further support in vivo testing of BETi-based combinations with JAKi and HSP90i against post-MPN sAML cells. PMID- 27677743 TI - The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation. AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin beta-4, eukaryotic translation initiation factor 4gamma2, fibrinogen beta-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention. PMID- 27677745 TI - Transition from paediatric to adult care of adolescent patients with congenital heart disease: a pathway to optimal care. AB - INTRODUCTION: Adolescents with congenital heart disease transition from a paediatric to an adult setting. This is associated with loss-to-follow-up and suboptimal care. Increasing numbers of patients justify a special program. In this study we evaluated the cooperative program between paediatric and adult cardiology departments in a tertiary referral centre. METHODS: In this retrospective study, patients with congenital heart disease with at least one appointment scheduled at the transition program between January 2010 and January 2015 were included. They were seen by a paediatric cardiologist at the age of 15 years in the paediatric department and from age 18 to 25 in the adult department. Demographic and medical data were collected from the electronic patient files. RESULTS: A total of 193 patients (105 males, 88 females) were identified. Sex distribution was almost equal. Most patients were 18-21 years of age. The largest group, 128 patients (67 %), lived within 50 kilometres of our hospital. Paediatric cardiologists referred 157 (81 %) of patients. General practitioners and cardiologists from outside our centre were important referrers for patients lost to follow-up, together accounting for 9 %. A total of 34 (18 %) patients missed an appointment without notification. Repeat offenders, 16 of 34 patients, formed a significant minority within this group. A total of 114 (59 %) patients were attending school, 46 (24 %) were employed, and 33 (17 %) patients were inactive. Activities are in line with capabilities. A nurse practitioner was involved with the 7 % with complex and psychosocial problems. Moderately severe congenital heart defects formed the largest patient category of 102 (53 %) patients. In 3 % of patients the diagnosis had to be revised or was significantly incomplete. In 30 (16 %) patients, cardiac diagnosis was part of a syndrome. Of the 193 patients, 117 (92 %) were in NYHA class I, with 12 (6 %) and 4 (2 %) patients falling into classes II and III, respectively. CONCLUSIONS: A viable transition program can be built by collaboration between paediatric and adult cardiology departments with the same treating physician taking care of patients between 15 and 25 years of age. General practitioners are important in returning lost-to-follow-up patients to specialised care. Nurse practitioners are essential in the care for patients with complex congenital heart disease. PMID- 27677741 TI - Pharmacogenomics and chemical library screens reveal a novel SCFSKP2 inhibitor that overcomes Bortezomib resistance in multiple myeloma. AB - While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin ligase Skp1-Cullin 1-Skp2 (SCFSkp2) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCFSkp2 activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B. Here we observed higher CUL1, COMMD1 and SKP2 mRNA levels in CD138+ cells isolated from BTZ-resistant MM patients. Higher CUL1, COMMD1, SKP2 and CKS1B mRNA levels in patient CD138+ cells correlated with decreased progression-free and overall survival. Genetic knockdown of CUL1, COMMD1 or SKP2 disrupted the SCFSkp2 complex, stabilized p27 and increased the number of annexin V-positive cells after BTZ treatment. Chemical library screens identified a novel compound, designated DT204, that reduced Skp2 binding to Cullin-1 and Commd1, and synergistically enhanced BTZ-induced apoptosis. DT204 co-treatment with BTZ overcame drug resistance and reduced the in vivo growth of myeloma tumors in murine models with survival benefit. Taken together, the results provide proof of concept for rationally designed drug combinations that incorporate SCFSkp2 inhibitors to treat BTZ resistant disease. PMID- 27677744 TI - Cardiac sympathetic activity in chronic heart failure: cardiac 123I-mIBG scintigraphy to improve patient selection for ICD implantation. AB - Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with 123I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation. PMID- 27677742 TI - B cells and macrophages pursue a common path toward the development and progression of chronic lymphocytic leukemia. AB - The development and progression of chronic B-cell tumors depend on a complex microenvironmental network of cells that include monocyte-derived macrophages. In chronic lymphocytic leukemia (CLL) the survival of malignant cells is supported in vitro by nurse-like cells, which differentiate from CD14+ monocytes and have been identified as tumor-associated macrophages (TAMs). The role of the monocyte/macrophage lineage in CLL has been extensively studied in vitro, but only recently has been investigated in in vivo models. We here discuss how the cellular and molecular interactions that physiologically occur between B cells and macrophages can be subverted in chronic B lymphoid malignancies. Clinical approaches for the therapeutic targeting of TAMs are under evaluation. Promising strategies, along with a direct impact on the malignant cells, affect crucial pathways involved in the interaction of leukemic cells with TAMs. As an example, ibrutinib reduces CLL cell chemoattraction by inhibiting macrophage secretion of CXCL13. Lenalidomide and trabectedin prevent TAM recruitment mainly through CCL2 blockade. Most advanced strategies aim at depleting macrophages by targeting the CSF1/CSF1R pathway, which is fundamental for TAM survival. Of note, CSF1 transcripts are significantly more abundant in progressive CLL patients when compared with stable CLL and the frequency of CSF1R+ TAMs correlates with poor survival in hematological malignancies. The successful combination of CSF1R inhibition with currently available agents targeting malignant cells might represent the next therapeutic frontier in CLL. Conceivably these approaches may become applicable to numerous chronic B lymphoid malignancies. PMID- 27677746 TI - Syngas obtained by microwave pyrolysis of household wastes as feedstock for polyhydroxyalkanoate production in Rhodospirillum rubrum. AB - The massive production of urban and agricultural wastes has promoted a clear need for alternative processes of disposal and waste management. The potential use of municipal solid wastes (MSW) as feedstock for the production of polyhydroxyalkanoates (PHA) by a process known as syngas fermentation is considered herein as an attractive bio-economic strategy to reduce these wastes. In this work, we have evaluated the potential of Rhodospirillum rubrum as microbial cell factory for the synthesis of PHA from syngas produced by microwave pyrolysis of the MSW organic fraction from a European city (Seville). Growth rate, uptake rate, biomass yield and PHA production from syngas in R. rubrum have been analysed. The results revealed the strong robustness of this syngas fermentation where the purity of the syngas is not a critical constraint for PHA production. Microwave-induced pyrolysis is a tangible alternative to standard pyrolysis, because it can reduce cost in terms of energy and time as well as increase syngas production, providing a satisfactory PHA yield. PMID- 27677747 TI - Splenic metastasis in colorectal cancer. PMID- 27677748 TI - Biodegradation and metabolic pathway of nicotine in Rhodococcus sp. Y22. AB - Nicotine in tobacco is harmful to health and the environment, so there is an environmental requirement to remove nicotine from tobacco and tobacco wastes. In this study, the biotransformation of nicotine by Rhodococcus sp. Y22 was investigated, and three metabolites (NIC1, NIC4 and NIC5) were isolated by column separation, preparative TLC and solid plate's method, respectively. NIC1 was identified as 6-hydoxynicotine based on the results of NMR, MS, HPLC-UV and HRESIMS analysis; NIC4 was a novel compound and identified as 5-(3-methyl [1,3]oxazinan-2-ylidene)-5H-pyridin-2-one based on the results of NMR, MS and UV analysis; NIC5 was identified as nicotine blue based on the results of NMR and MS analysis. Meanwhile, two metabolites NIC2 and NIC3 were identified as 6-hydroxy-N methylmyosmine and 6-hydroxypseudooxynicotine by HRESIMS analysis, respectively. According to these metabolites, the possible pathway of nicotine degradation by Rhodococcus sp. Y22 was proposed. The nicotine can be transformed to nicotine blue through two pathways (A and B), and 6-hydroxy-N-methylmyosmine is the key compound, which can be converted to 6-hydroxypseudooxynicotine (pathway A) and 5 (3-methyl-[1,3]oxazinan-2-ylidene)-5H-pyridin-2-one (pathway B), respectively. Moreover, the encoding gene of nicotine dehydrogenase, ndh, was amplified from Rhodococcus sp. Y22, and its transcriptional level could be up-regulated obviously under nicotine induction. Our studies reported the key metabolites and possible biotransformation pathway of nicotine in Rhodococcus sp. Y22, and provided new insights into the microbial metabolism of nicotine. PMID- 27677749 TI - Absolute binding free energy calculations of CBClip host-guest systems in the SAMPL5 blind challenge. AB - Herein, we report the absolute binding free energy calculations of CBClip complexes in the SAMPL5 blind challenge. Initial conformations of CBClip complexes were obtained using docking and molecular dynamics simulations. Free energy calculations were performed using thermodynamic integration (TI) with soft core potentials and Bennett's acceptance ratio (BAR) method based on a serial insertion scheme. We compared the results obtained with TI simulations with soft core potentials and Hamiltonian replica exchange simulations with the serial insertion method combined with the BAR method. The results show that the difference between the two methods can be mainly attributed to the van der Waals free energies, suggesting that either the simulations used for TI or the simulations used for BAR, or both are not fully converged and the two sets of simulations may have sampled difference phase space regions. The penalty scores of force field parameters of the 10 guest molecules provided by CHARMM Generalized Force Field can be an indicator of the accuracy of binding free energy calculations. Among our submissions, the combination of docking and TI performed best, which yielded the root mean square deviation of 2.94 kcal/mol and an average unsigned error of 3.41 kcal/mol for the ten guest molecules. These values were best overall among all participants. However, our submissions had little correlation with experiments. PMID- 27677750 TI - Blind prediction of cyclohexane-water distribution coefficients from the SAMPL5 challenge. AB - In the recent SAMPL5 challenge, participants submitted predictions for cyclohexane/water distribution coefficients for a set of 53 small molecules. Distribution coefficients (log D) replace the hydration free energies that were a central part of the past five SAMPL challenges. A wide variety of computational methods were represented by the 76 submissions from 18 participating groups. Here, we analyze submissions by a variety of error metrics and provide details for a number of reference calculations we performed. As in the SAMPL4 challenge, we assessed the ability of participants to evaluate not just their statistical uncertainty, but their model uncertainty-how well they can predict the magnitude of their model or force field error for specific predictions. Unfortunately, this remains an area where prediction and analysis need improvement. In SAMPL4 the top performing submissions achieved a root-mean-squared error (RMSE) around 1.5 kcal/mol. If we anticipate accuracy in log D predictions to be similar to the hydration free energy predictions in SAMPL4, the expected error here would be around 1.54 log units. Only a few submissions had an RMSE below 2.5 log units in their predicted log D values. However, distribution coefficients introduced complexities not present in past SAMPL challenges, including tautomer enumeration, that are likely to be important in predicting biomolecular properties of interest to drug discovery, therefore some decrease in accuracy would be expected. Overall, the SAMPL5 distribution coefficient challenge provided great insight into the importance of modeling a variety of physical effects. We believe these types of measurements will be a promising source of data for future blind challenges, especially in view of the relatively straightforward nature of the experiments and the level of insight provided. PMID- 27677751 TI - Blinded predictions of distribution coefficients in the SAMPL5 challenge. AB - In the context of the SAMPL5 challenge water-cyclohexane distribution coefficients for 53 drug-like molecules were predicted. Four different models based on molecular dynamics free energy calculations were tested. All models initially assumed only one chemical state present in aqueous or organic phases. Model A is based on results from an alchemical annihilation scheme; model B adds a long range correction for the Lennard Jones potentials to model A; model C adds charging free energy corrections; model D applies the charging correction from model C to ionizable species only. Model A and B perform better in terms of mean unsigned error ([Formula: see text] D units - 95 % confidence interval) and determination coefficient [Formula: see text], while charging corrections lead to poorer results with model D ([Formula: see text] and [Formula: see text]). Because overall errors were large, a retrospective analysis that allowed co existence of ionisable and neutral species of a molecule in aqueous phase was investigated. This considerably reduced systematic errors ([Formula: see text] and [Formula: see text]). Overall accurate [Formula: see text] predictions for drug-like molecules that may adopt multiple tautomers and charge states proved difficult, indicating a need for methodological advances to enable satisfactory treatment by explicit-solvent molecular simulations. PMID- 27677752 TI - Grebe dysplasia - prenatal diagnosis based on rendered 3-D ultrasound images of fetal limbs. AB - Grebe dysplasia is a rare skeletal dysplasia characterized by severe acromesomelic shortening of the long bones in a proximal to distal gradient of severity, with bones of the hands and feet more severely affected than those of the forearms and legs, which in turn are more severely affected than the humeri and femora. In addition, the bones of the lower extremities tend to be more severely affected than the bones of the upper extremities. Despite the severe skeletal deformities, the condition is not lethal and surviving individuals can have normal intelligence. Herein we report a case of Grebe dysplasia diagnosed at 20 weeks of gestation. Rendered 3-D ultrasound images of the fetal limbs, particularly of the characteristic tiny and globular-looking fingers and toes, were instrumental in accurately characterizing the phenotype prenatally. PMID- 27677753 TI - Relation between extinction and assisted colonization of plants in the arctic alpine and boreal regions. AB - Assisted colonization of vascular plants is considered by many ecologists an important tool to preserve biodiversity threatened by climate change. I argue that assisted colonization may have negative consequences in arctic-alpine and boreal regions. The observed slow movement of plants toward the north has been an argument for assisted colonization. However, these range shifts may be slow because for many plants microclimatic warming (ignored by advocates of assisted colonization) has been smaller than macroclimatic warming. Arctic-alpine and boreal plants may have limited possibilities to disperse farther north or to higher elevations. I suggest that arctic-alpine species are more likely to be driven to extinction because of competitive exclusion by southern species than by increasing temperatures. If so, the future existence of arctic-alpine and boreal flora may depend on delaying or preventing the migration of plants toward the north to allow northern species to evolve to survive in a warmer climate. In the arctic-alpine region, preventing the dispersal of trees and shrubs may be the most important method to mitigate the negative effects of climate change. The purported conservation benefits of assisted colonization should not be used to promote the migration of invasive species by forestry. PMID- 27677754 TI - Developing FT-NIR and PLS1 Methodology for Predicting Adulteration in Representative Varieties/Blends of Extra Virgin Olive Oils. AB - It was previously demonstrated that Fourier transform near infrared (FT-NIR) spectroscopy and partial least squares (PLS1) were successfully used to assess whether an olive oil was extra virgin, and if adulterated, with which type of vegetable oil and by how much using previously developed PLS1 calibration models. This last prediction required an initial set of four PLS1 calibration models that were based on gravimetrically prepared mixtures of a specific variety of extra virgin olive oil (EVOO) spiked with adulterants. The current study was undertaken after obtaining a range of EVOO varieties grown in different countries. It was found that all the different types of EVOO varieties investigated belonged to four distinct groups, and each required the development of additional sets of specific PLS1 calibration models to ensure that they can be used to predict low concentrations of vegetable oils high in linoleic, oleic, or palmitic acid, and/or refined olive oil. These four distinct sets of PLS1 calibration models were required to cover the range of EVOO varieties with a linoleic acid content from 1.3 to 15.5 % of total fatty acids. An FT-NIR library was established with 66 EVOO products obtained from California and Europe. The quality and/or purity of EVOO were assessed by determining the FT-NIR Index, a measure of the volatile content of EVOO. The use of these PLS1 calibration models made it possible to predict the authenticity of EVOO and the identity and quantity of potential adulterant oils in minutes. PMID- 27677757 TI - ? PMID- 27677756 TI - Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task. AB - Different lines of research suggest that anxiety-related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self-motion. Twenty-four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self motion (vertical motion), and (2) trials simulating self-motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto-insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo vestibular and anxiety-related systems during simulated vertical self-motion. Hum Brain Mapp 38:715-726, 2017. (c) 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID- 27677755 TI - Anti-regulatory T cells. AB - Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells-termed anti-regulatory T cells (anti Tregs)-that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells, including indoleamine 2,3-dioxygenase (IDO), tryptophan 2,6-dioxygenase (TDO), programmed death-ligand 1 (PD-L1), and forkhead box P3 (Foxp3). These proteins are highly expressed in professional antigen-presenting cells under various physiological conditions, such as inflammation and stress. Therefore, self-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles in immune homeostasis and their potential future clinical applications. PMID- 27677759 TI - [Therapeutic plasma exchange for the treatment of hypertriglyceridemia-induced pancreatitis : A case report]. AB - A rare but serious form of pancreatitis is caused by severe hypertriglyceridemia. It accounts for up to 10 % of all acute pancreatitis episodes. Despite a pathophysiology that differs distinctly from other forms of pancreatitis, there are no accepted guidelines for the treatment of hypertriglyceridemia-induced pancreatitis. We report a morbidly obese (BMI 45 kg/m2) 36-year-old Caucasian woman with a history of schizophrenic psychosis who was transferred to our tertiary care hospital for further diagnosis and treatment of increasing abdominal pain and hypertryglyceridemia of 2757 mg/dl. Due to rapid clinical deterioration, requiring invasive mechanical ventilation we performed therapeutic plasma exchange (TPE). About 1.5 times of the patient's calculated plasma volume was exchanged using fresh frozen plasma as substitution fluid. After a single TPE the triglyceride levels decreased by 86 % to 387 mg/dl. Concomitantly C-reactive protein decreased from 303 to 179 mg/dl. Despite the paucity of data, TPE may be a beneficial means to lower triglycerides in patients with hypertriglyceridemia induced pancreatitis, due to the rapid removal of the causative agent leading to pancreatic injury. PMID- 27677758 TI - [Current recommendations for basic/advanced life support : Addressing unanswered questions and future prospects]. AB - The revised guidelines for cardiopulmonary resuscitation were implemented by the European Resuscitation Council (ERC) in October 2015. There were few changes concerning basic and advanced life support; however, some issues were clarified compared to the ERC recommendations from 2010. The present paper summarizes the procedures of basic and advanced life support according to the current guidelines and highlights the updates of 2015. Furthermore, the article depicts future prospects of cardiopulmonary resuscitation that may improve outcome of patients after cardiac arrest in the future. PMID- 27677760 TI - Serum IgG levels and mortality in patients with severe sepsis and septic shock : The SBITS data. AB - BACKGROUND: The role of intravenous immune globulin (Ig) therapy in patients with severe sepsis and septic shock is discussed controversially. Low initial IgG levels could help to identify those patients who might benefit from an adjunctive Ig treatment. OBJECTIVES: To investigate the effect of initial serum IgG levels on 28-day mortality in patients with severe sepsis and septic shock. MATERIALS AND METHODS: In this retrospective analysis of the SBITS trial data, 543 patients were allocated to four groups (quartiles) depending on their initial serum IgG levels (1: IgG <= 6.1 g/l; 2: IgG 6.2-8.4 g/l; 3: IgG 8.5-11.9 g/l; 4: IgG > 11.9 g/l). The third quartile was taken as the reference quartile. For the applied logistic regression model clinically relevant confounders were defined and integrated into further risk-adjusted calculations. RESULTS: Patients with the lowest IgG levels had a mortality rate similar to those patients with initial IgG levels in the second and third quartile, representing the physiological IgG range in healthy people. Surprisingly, patients with the highest IgG levels even showed a significantly higher mortality in a risk-adjusted calculation compared to the reference quartile (OR 1.69, CI 1.01-2.81, p = 0.05). Subgroup analyses revealed that initial IgG levels were of no prognostic value in patients presenting with vasopressor-dependent septic shock on admission as well as in patients with either gram-positive or gram-negative sepsis. CONCLUSIONS: Initially low IgG levels do not discriminate between survival and nonsurvival in patients with severe sepsis and septic shock. Therefore, low IgG cannot help to identify those patients who might benefit from an adjunctive IgG sepsis therapy. Whether a high initial IgG serum level is an independent mortality risk factor needs to be investigated prospectively. PMID- 27677761 TI - National trends among radiologists in reporting coronary artery calcium in non gated chest computed tomography. AB - Coronary artery calcification (CAC) is a known risk factor for adverse outcomes in the general population and in patients with coronary artery disease. We performed a survey of United States radiologists to evaluate the trends in reporting the presence or absence of CAC on NCCT examinations. An 11 multiple choice questionnaire was distributed to members of the American College of Radiology, and 530 members participated in the study. Eighty-seven percent of the analyzed group report the presence of CAC on standard CT scans of the chest, and approximately half them (52 %) use a qualitative modifier. Only 32 % of cardiac imagers were aware of the published data correlating qualitative and quantitative calcium scores on non-gated chest CT examinations compared to 17 % of non-cardiac imagers. We believe that subjective or objective grading of coronary calcified plaque burden on standard chest CT exams is warranted as it may not only help risk-stratify patients, but also may eliminate the need for dedicated CACS in many patients and may be useful in treatment guidance. PMID- 27677762 TI - Three-dimensional printed models in congenital heart disease. AB - The purpose of this article is to discuss technical considerations and current applications of three-dimensional (3D) printing in congenital heart disease (CHD). CHD represent an attractive field for the application of 3D printed models, with consistent progress made in the past decade. Current 3D models are able to reproduce complex cardiac and extra-cardiac anatomy including small details with very limited range of errors (<1 mm), so this tool could be of value in the planning of surgical or percutaneous treatments for selected cases of CHD. However, the steps involved in the building of 3D models, consisting of image acquisition and selection, segmentation, and printing are highly operator dependent. Current 3D models may be rigid or flexible, but unable to reproduce the physiologic variations during the cardiac cycle. Furthermore, high costs and long average segmentation and printing times (18-24 h) limit a more extensive use. There is a need for better standardization of the procedure employed for collection of the images, the segmentation methods and processes, the phase of cardiac cycle used, and in the materials employed for printing. More studies are necessary to evaluate the diagnostic accuracy and cost-effectiveness of 3D printed models in congenital cardiac care. PMID- 27677763 TI - The multi-ethnic global lung initiative 2012 and Third National Health and Nutrition Examination Survey reference values do not reflect spirometric measurements in Black boys and men from Tanzania. AB - The interpretation of spirometric results of Black Africans according to reference standards based on data from outside their native environment may lead to the wrong conclusions. This article aims to characterize the ventilatory capacity of boys and men from Tanzania according to forced expiratory volume in one second (FEV1 ), forced vital capacity (FVC), peak expiratory flow (PEF) and FEV1 /FVC based on the collected anthropological material and to compare them to NHANES III, Third National Health and Nutrition Examination Survey (NHANES III) African American predicted values and GLI2012 equations. The analysis included spirometric measurements of n = 295 participants from Tanzania. Pearson's correlation analysis and the backward stepwise multiple regression analysis were performed. FEV1 , FVC, PEF and FEV1 /FVC results were compared to the NHANES III African American predicted values as well as to the GLI2012 equations. FEV1 measurements are lower than the reference values according to NHANES III and GLI2012 equations by 22.1% and 25.8%. FVC results fell short of the NHANES III predicted by 29.5% and of GLI2012 by 32.5%. The average %FEV1 /FVC scores for the boys and men exceeded the recommended GLI2012 predicted by 10.5-15.2%. All the spirometric measurements included in the analysis were statistically significantly correlated with age, body height, sitting height, trunk length and body weight. The application of prediction formulae developed for non-African populations overestimates the values for Black Africans. The results of spirometric measurements are ecosensitive and dependent on various external (environmental) factors. PMID- 27677764 TI - A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice. AB - AIMS/HYPOTHESIS: To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions. METHODS: Atgl flox/flox mice were cross-bred with Mip-Cre-ERT mice to generate Mip-Cre-ERT/+;Atgl flox/flox mice. At 8 weeks of age, these mice were injected with tamoxifen to induce deletion of beta cell-specific Atgl (also known as Pnpla2), and the mice were fed an ND or HFD. RESULTS: ND-fed male B-Atgl-KO mice showed decreased insulinaemia and glucose-induced insulin secretion (GSIS) in vivo. Changes in GSIS correlated with the islet content of long-chain saturated monoacylglycerol (MAG) species that have been proposed to be metabolic coupling factors for insulin secretion. Exogenous MAGs restored GSIS in B-Atgl-KO islets. B-Atgl-KO male mice fed an HFD showed reduced insulinaemia, glycaemia in the fasted and fed states and after glucose challenge, as well as enhanced insulin sensitivity. Moreover, decreased insulinaemia in B-Atgl-KO mice was associated with increased energy expenditure, and lipid metabolism in brown (BAT) and white (WAT) adipose tissues, leading to reduced fat mass and body weight. CONCLUSIONS/INTERPRETATION: ATGL in beta cells regulates insulin secretion via the production of signalling MAGs. Decreased insulinaemia due to lowered GSIS protects B-Atgl-KO mice from diet-induced obesity, improves insulin sensitivity, increases lipid mobilisation from WAT and causes BAT activation. The results support the concept that fuel excess can drive obesity and diabetes via hyperinsulinaemia, and that an islet beta cell ATGL lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion. PMID- 27677766 TI - Steroid-induced hyperglycaemia in hospitalised patients: does it matter? AB - Steroid-induced hyperglycaemia is a common problem faced by endocrinologists in hospital wards. In this issue of Diabetologia, Popovic and colleagues (DOI 10.1007/s00125-016-4091-4 ) have conducted a subanalysis within a randomised controlled trial of prednisone therapy for community-acquired pneumonia. The authors found that the presence of diabetes or hyperglycaemia related to steroid therapy did not attenuate the clinical benefits of steroid therapy. The relevance and possible implications of these findings are discussed. PMID- 27677765 TI - Metabolic effects of orally administered small-molecule agonists of GPR55 and GPR119 in multiple low-dose streptozotocin-induced diabetic and incretin-receptor knockout mice. AB - AIMS/HYPOTHESIS: Abnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice. METHODS: Diabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS 1269574 (0.1 MUmol/kg) or saline vehicle (0.9% wt/vol. NaCl) over 28 days. Body weight, food intake, fluid intake, plasma glucose, insulin, glucose tolerance, insulin release, lipid profile and pancreatic morphology were examined. Mechanism of action of agonists was assessed in acute studies using incretin-receptor knockout mice. RESULTS: Abn-CBD and AS-1269574 decreased plasma glucose (20-26%, p < 0.05) and increased circulating insulin (47-48%, p < 0.05) by 10-28 days, compared with saline-treated diabetic controls. Food intake and polydipsia were reduced by both agonists (21-23%, p < 0.05 and 33-35%, p < 0.01, respectively). After 28 days of treatment, plasma glucagon concentrations were reduced (p < 0.01) and glucose tolerance was enhanced by 19-44% by Abn-CBD (p < 0.05 or p < 0.001) and AS-1269574 (p < 0.05 to p < 0.001). Plasma insulin responses were improved (p < 0.01) and insulin resistance was decreased (p < 0.05 or p < 0.01) in both Abn-CBD- and AS-1269574-treated groups. Triacylglycerols were decreased by 19% with Abn-CBD (p < 0.05) and 32% with AS-1269574 (p < 0.01) while total cholesterol was reduced by 17% (p < 0.01) and 15% (p < 0.05), respectively. Both agonists enhanced beta cell proliferation (p < 0.001) although islet area was unchanged. Acute studies in Gipr- and Glp1r-knockout mice revealed an important role for the glucagon-like peptide 1 (GLP-1) receptor in the actions of both agonists, with the glucose-lowering effects of Abn-CBD also partly mediated through the glucose-dependent insulinotropic peptide (GIP) receptor. CONCLUSIONS/INTERPRETATION: These data highlight the potential for fatty acid G protein-coupled receptor-based therapies as novel insulinotropic and glucose lowering agents acting partly through the activation of incretin receptors. PMID- 27677767 TI - Comparison of in Silico, Electrochemical, in Vitro and in Vivo Metabolism of a Homologous Series of (Radio)fluorinated sigma1 Receptor Ligands Designed for Positron Emission Tomography. AB - The imaging of sigma1 receptors in the brain by fluorinated radiotracers will be used for the validation of sigma1 receptors as drug targets as well as for differential diagnosis of diseases in the central nervous system. The biotransformation of four homologous fluorinated PET tracers 1'-benzyl-3-(omega fluoromethyl to omega-fluorobutyl)-3H-spiro[2]benzofuran-1,4'-piperidine] ([18 F]1-4) was investigated. In silico studies using fast metabolizer (FAME) software, electrochemical oxidations, in vitro studies with rat liver microsomes, and in vivo metabolism studies after application of the PET tracers [18 F]1-4 to mice were performed. Combined liquid chromatography and mass spectrometry (HPLC MS) analysis allowed structural identification of non-radioactive metabolites. Radio-HPLC and radio-TLC provided information about the presence of unchanged parent radiotracers and their radiometabolites. Radiometabolites were not found in the brain after application of [18 F]2-4, but liver, plasma, and urine samples contained several radiometabolites. Less than 2 % of the injected dose of [18 F]4 reached the brain, rendering [18 F]4 less appropriate as a PET tracer than [18 F]2 and [18 F]3. Compounds [18 F]2 and [18 F]3 possess the most promising properties for imaging of sigma1 receptors in the brain. High sigma1 affinity (Ki =0.59 nm), low lipophilicity (logD7.4 =2.57), high brain penetration (4.6 % of injected dose after 30 min), and the absence of radiometabolites in the brain favor the fluoroethyl derivative [18 F]2 slightly over the fluoropropyl derivative [18 F]3 for human use. PMID- 27677769 TI - Erosion and sedimentation during the September 2015 flooding of the Kinu River, central Japan. AB - Erosional and sedimentary features associated with flooding have been documented in both modern and past cases. However, only a few studies have demonstrated the relationship between these features and the corresponding hydraulic conditions that produced them, making it difficult to evaluate the magnitude of paleo flooding. This study describes the characteristics associated with inundation depth and flow direction, as well as the erosional and sedimentary features resulting from the disastrous flooding of the Kinu River, central Japan, in September 2015. Water levels rose rapidly due to heavy rainfall that eventually overtopped, and subsequently breached, a levee in Joso City, causing destructive flooding on the surrounding floodplain. Distinctive erosional features are found next to the breached levee, while depositional features, such as a sandy crevasse splay deposit are found further away from the breach. The deposit can be divided into three units based on sedimentary facies. The vertical and lateral changes of these sedimentary facies may be the result of temporal and spatial changes associated with flow during the single flooding event. These observations and quantitative data provide information that can be used to reveal the paleohydrology of flood deposits in the stratigraphic record, leading to improved mitigation of future flooding disasters. PMID- 27677768 TI - CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients. AB - T cell immunoglobulin mucin domain-1(Tim-1) was recently identified to be critical and essential for optimal regulatory B cells function in maintaining immune tolerance. We aimed to measure the expression levels of Tim-1 on B cells from patients with Myasthenia Gravis (MG) and to investigate whether the expression of Tim-1 is associated with pathogenesis of MG. A total of 34 patients with MG (18 generalized MG (GMG) and 16 ocular MG (OMG) and 24 healthy donors were recruited in this study. The quantitative myasthenia gravis score (QMGS) was used to evaluate the clinical severity. Real-time PCR and flow cytometry were used to measure the levels of Tim-1 expressed on peripheral B cells. Peripheral CD138+ plasma cells were assayed by flow cytometry. Serum Th17-related cytokines (IL-6, IL-1beta and IL-17) and anti-AChR antibody (Ab) titers were tested by enzyme-linked immunosorbent assay (ELISA). Our data demonstrated that the mRNA and protein expression levels of B cell Tim-1 in both the GMG and OMG groups were significantly lower than those in healthy controls, with lower expression in GMG than in OMG. Tim-1 expression on B cells from OMG/GMG was negatively correlated with clinical severity, plasma cells frequency, serum Th17-related cytokines and anti-AChR Ab levels. Our results indicated that aberrant expression of Tim-1 exists on B cells and may contribute to the Th17 polarization and antibody secreting plasma cells differentiation in MG patients. PMID- 27677770 TI - Can myocardial performance index predict the presence of silent ischemia in asymptomatic type 2 diabetic patients? AB - BACKGROUND: Coronary artery disease (CAD) is an important cause of morbidity and mortality in patients with diabetes. Silent myocardial ischemia (SMI) is common in patients with diabetes and is associated with poorer prognosis. Myocardial performance index "Tei index" that reflects both left ventricular (LV) systolic and diastolic function. The aim of our study was to test the value of Tei index in prediction of SMI in asymptomatic patients with type 2 diabetes. PATIENTS AND METHODS: Asymptomatic patients with type 2 diabetes were included in our study. We excluded patients with known CAD, previous revascularization, low ejection fraction, or abnormal ECG from the study. All patients had undergone history taking and clinical examination, ECG, echocardiography with measuring of Tei index and Holter monitoring for detecting silent ischemia. RESULTS: A total of 200 patients were recruited. We divided our patients into two groups: Group I: 64 patients with SMI, Group II: 136 patients without SMI. There was no significant difference between the two groups regarding clinical and conventional echocardiographic data. Tei index was significantly higher in patients with silent ischemia (P<.00001). Sensitivity, specificity, positive, and negative predictive values of Tei index >=0.6 in prediction of Holter detected silent ischemia were 85.9%, 90%, 78.6%, and 88.6%, respectively. We found a significant positive correlation between Tei index and number of ischemic episodes (r=.366, P=.0029). CONCLUSION: Measuring Tei index is helpful in predicting the presence of silent ischemia in asymptomatic patients with type 2 diabetes. PMID- 27677772 TI - Future jobs of FDA's haematology-oncology reviewers. PMID- 27677771 TI - Complex PTSD as proposed for ICD-11: validation of a new disorder in children and adolescents and their response to Trauma-Focused Cognitive Behavioral Therapy. AB - BACKGROUND: To evaluate whether the symptoms of children and adolescents with clinically significant posttraumatic stress symptoms (PTSS) form classes consistent with the diagnostic criteria of complex PTSD (CPTSD) as proposed for the ICD-11, and to relate the emerging classes with treatment outcome of Trauma Focused Cognitive Behavioral Therapy (TF-CBT). METHODS: Latent classes analysis (LCA) was used to explore the symptom profiles of the clinical baseline assessment of N = 155 children and adolescents participating in a randomized controlled trial of TF-CBT. The treatment outcomes of patients with posttraumatic stress disorder (PTSD) and of patients with CPTSD were compared by a t-test for depended samples and a repeated-measures ANOVA. RESULTS: The LCA revealed two distinct classes: a PTSD class characterized by elevated core symptoms of PTSD (n = 62) and low symptoms of disturbances in self-organization versus a complex PTSD class with elevated PTSD core symptoms and elevated symptoms of disturbances in self-organization (n = 93). The Group * Time interaction regarding posttraumatic stress symptoms was not significant. Pre-post effect sizes regarding posttraumatic stress symptoms were large for both groups (PTSD: d = 2.81; CPTSD: d = 1.37). For disturbances in self-organization in the CPTSD class, we found medium to large effect sizes (d = 0.40-1.16) after treatment with TF-CBT. CONCLUSIONS: The results provide empirical evidence of the ICD-11 CPTSD and PTSD distinction in a clinical sample of children and adolescents. In terms of relative improvement from their respective baseline posttraumatic stress symptoms, patients with PTSD and CPTSD responded equally to TF-CBT; however, those with CPTSD ended treatment with clinically and statistically greater symptoms than those with PTSD. PMID- 27677773 TI - Patient-Centered Interventions to Improve Adherence to Statins: A Narrative Synthesis of Systematically Identified Studies. AB - Poor adherence to statins increases cardiovascular disease risk. We systematically identified 32 controlled studies that assessed patient-centered interventions designed to improve statin adherence. The limited number of studies and variation in study characteristics precluded strict quality criteria or meta analysis. Cognitive education or behavioural counselling delivered face-to-face multiple times consistently improved statin adherence compared with control groups (7/8 and 3/3 studies, respectively). None of four studies using medication reminders and/or adherence feedback alone reported significantly improved statin adherence. Single interventions that improved statin adherence but were not conducted face-to-face included cognitive education in the form of genetic test results (two studies) and cognitive education via a website (one study). Similar mean adherence measures were reported for 17 intervention arms and were thus compared in a sub-analysis: 8 showed significantly improved statin adherence, but effect sizes were modest (+7 to +22 % points). In three of these studies, statin adherence improved despite already being high in the control group (82-89 vs. 57 69 % in the other studies). These three studies were the only studies in this sub analysis to include cognitive education delivered face-to-face multiple times (plus other interventions). In summary, the most consistently effective interventions for improving adherence to statins have modest effects and are resource-intensive. Research is needed to determine whether modern communications, particularly mobile health platforms (recently shown to improve medication adherence in other chronic diseases), can replicate or even enhance the successful elements of these interventions while using less time and fewer resources. PMID- 27677774 TI - Green synthesis of silver nanoparticles using Pongamia pinnata seed: Characterization, antibacterial property, and spectroscopic investigation of interaction with human serum albumin. AB - In recent years, green synthesized nanoparticles from plant extract have drawn a great interest due to their prospective nanomedicinal application. This study investigates a proficient, safer, and sustainable way for the preparation of AgNPs using medicinal plant Pongamia pinnata (family: Leguminoseae, species: Pinnata) seeds extract without using any external reducing and stabilizing agent. Both ultraviolet-visible spectrum at lambdamax = 439 nm and energy dispersive X ray spectra proof the formation of AgNPs. An average diameter of the AgNPs was 16.4 nm as revealed from transmission electron microscope. Hydrodynamic size (d = ~19.6 nm) was determined by dynamic light scattering (DLS). Zeta potential of AgNPs was found to be -23.7 mV, which supports its dispersion and stability. Fourier transform infrared study revealed that the O ? H, C ? O, and C-O-C groups were responsible for the formation of AgNPs. The antibacterial activity of the synthesized AgNPs was checked against Escherichia coli ATCC 25922. AgNPs at its LD50 dose exhibited synergistic effect with ampicillin. Because protein-AgNPs association greatly affects its adsorption, distribution, and functionality and can also influence the functions of biomolecules. So in order to understand the adsorption and bioavailability, we investigated by fluorescence, ultraviolet visible, and circular dichroism spectroscopic methods the interaction of synthesized AgNPs toward human serum albumin. The binding affinity and binding sites of human serum albumin toward AgNPs were measured by using the fluorescence quenching data. The circular dichroism spectroscopic results revealed that there was a negligible change of alpha-helical content in their native structure. Overall, these AgNPs show versatile biological activities and may be applied in the field of nanomedicine. PMID- 27677776 TI - Habit Formation and the Striatum. AB - Data from experimental animals and human subjects has provided convergent evidence for the key role of the striatum in the formation of stimulus-response habits. Habits can be distinguished from associative memories that support goal directed actions based on their insensitivity to reward devaluation and contingency degradation. Behavior on many instrumental learning tasks can be supported by both declarative knowledge and habits, and these contributions shift with the amount of training. This shift appears to be accompanied by the involvement of different cortico-striatal loops in controlling behavior. Factors that encourage the shift toward and maintenance of habits include learning under conditions of stress, distraction, and interval or probabilistic schedules of reinforcement. PMID- 27677775 TI - Liver injury from herbal and dietary supplements. AB - Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373). PMID- 27677777 TI - The Representational Basis of Working Memory. AB - Working memory refers to a system involved in the online maintenance and manipulation of information in the absence of external input. Due to the importance of working memory in higher-level cognition, a wealth of neuroscience studies has investigated its neural basis. These studies have often led to conflicting viewpoints regarding the importance of the prefrontal cortex (PFC) and posterior sensory cortices. Here, we review evidence for each position. We suggest that the relative contributions of the PFC and sensory cortices to working memory can be understood with respect to processing demands. We argue that procedures that minimize processing demands lead to increased importance of sensory representations, while procedures that permit transformational processing lead to representational abstraction that relies on the PFC. We suggest that abstract PFC representations support top-down control over posterior representations while also providing bottom-up inputs into higher-level cognitive processing. Although a number of contemporary studies have studied working memory while using procedures that minimize the role of the PFC, we argue that consideration of the PFC is critical for our understanding of working memory and higher-level cognition more generally. PMID- 27677778 TI - The Functional and Structural Neuroanatomy of Systems Consolidation for Autobiographical and Semantic Memory. AB - It is well established that patients with memory impairment have more difficulty retrieving memories from the recent past relative to the remote past and that damage to the medial temporal lobe (MTL) plays a key role in this pattern of impairment. The precise role of the MTL and how it may interact with other brain regions remains an area of active research. We investigated the role of structures in a memory network that supports remembering. Our chapter focuses on two types of memory: episodic memory and semantic memory. Findings from studies of patients with brain damage and neuroimaging studies in patients and healthy individuals were considered together to identify the functional and structural neuroanatomy of past remembrance. PMID- 27677779 TI - What Versus Where: Non-spatial Aspects of Memory Representation by the Hippocampus. AB - Since the discovery of place cells and other findings indicating strong involvement of the hippocampus in spatial information processing, there has been continued controversy about the extent to which the hippocampus also processes non-spatial aspects of experience. In recent years, many experiments studying the effects of hippocampal damage and characterizing hippocampal neural activity in animals and humans have revealed a clear and specific role of the hippocampus in the processing of non-spatial information. Here this evidence is reviewed in support of the notion that the hippocampus organizes the contents of memory in space, in time, and in networks of related memories. PMID- 27677780 TI - Exploration of the Neurobiological Basis for a Three-System, Multiattribute Model of Memory. AB - The structure and utilization of memory is central to one's knowledge of the past, interpretation of the present, and prediction of the future. Therefore, the understanding of the structural and process components of memory systems at the psychological and neurobiological level is of paramount importance. There have been a number of attempts to divide learning and memory into multiple memory systems. Schacter and Tulving, Memory systems 1994. MIT Press, Cambridge (1994) have suggested that one needs to define memory systems in terms of the kind of information to be represented, the processes associated with the operation of each system, and the neurobiological substrates, including neural structures and mechanisms, that subserve each system. Furthermore, it is likely that within each system there are multiple forms or subsystems associated with each memory system and there are likely to be multiple processes that define the operation of each system. Finally, there are probably multiple neural structures that form the overall substrate of a memory system. PMID- 27677781 TI - Immune-to-Brain Communication Pathways in Inflammation-Associated Sickness and Depression. AB - A growing body of evidence now highlights a key role for inflammation in mediating sickness behaviors and depression. Systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and chronic liver disease have high comorbidity with depression. How the periphery communicates with the brain to mediate changes in neurotransmission and thereby behavior is not completely understood. Traditional routes of communication between the periphery and the brain involve neural and humoral pathways with TNFalpha, IL-1beta, and IL 6 being the three main cytokines that have primarily been implicated in mediating signaling via these pathways. However, in recent years communication via peripheral immune-cell-to-brain and the gut-microbiota-to-brain routes have received increasing attention for their ability to modulate brain function. In this chapter we discuss periphery-to-brain communication pathways and their potential role in mediating inflammation-associated sickness behaviors and depression. PMID- 27677782 TI - MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment. AB - Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential dangers of MDMA in humans and the development of pharmacological tools to alleviate drug-induced hyperthermia - potentially saving the lives of highly intoxicated individuals. PMID- 27677784 TI - Role of Neuro-Immunological Factors in the Pathophysiology of Mood Disorders: Implications for Novel Therapeutics for Treatment Resistant Depression. AB - Mood disorders are associated with persistently high rates of morbidity and mortality, despite the widespread availability of antidepressant treatments. One limitation to extant therapeutic options has been that nearly all approved antidepressant pharmacotherapies exert a similar primary action of blocking monoamine transporters, and few options exist for transitioning treatment resistant patients to alternatives with distinct mechanisms. An emerging area of science that promises novel pathways to antidepressant and mood-stabilizing therapies has followed from evidence that immunological factors play major roles in the pathophysiology of at least some mood disorder subtypes. Here we review evidence that the compounds that reduce the release or signaling of neuroactive cytokines, particularly IL-1beta, IL-6, and TNF-alpha, can exert antidepressant effects in subgroups of depressed patients who are identified by blood-based biomarkers associated with inflammation. Within this context we discuss the role of microglia in central neuroinflammation, and the interaction between the peripheral immune system and the central synaptic microenvironment during and after neuroinflammation. Finally we review data using preclinical neuroinflammation models that produce depression-like behaviors in experimental animals to guide the discovery of novel neuro-immune drug targets. PMID- 27677783 TI - Electrophysiological Actions of Synthetic Cathinones on Monoamine Transporters. AB - Products containing psychoactive synthetic cathinones, such as mephedrone and 3,4 methylenedioxypyrovalerone (MDPV) are prevalent in our society. Synthetic cathinones are structurally similar to methamphetamine, and numerous synthetics have biological activity at dopamine, serotonin, and norepinephrine transporters. Importantly, monoamine transporters co-transport sodium ions along with their substrate, and movement of substrates and ions through the transporter can generate measurable ionic currents. Here we review how electrophysiological information has enabled us to determine how synthetic cathinones affect transporter-mediated currents in cells that express these transporters. Specifically, drugs that act as transporter substrates induce inward depolarizing currents when cells are held near their resting membrane potential, whereas drugs that act as transporter blockers induce apparent outward currents by blocking an inherent inward leak current. We have employed the two-electrode voltage-clamp technique in Xenopus laevis oocytes overexpressing monoamine transporters to determine whether synthetic cathinones found in the so-called bath salts products behave as blockers or substrates. We also examined the structure-activity relationships for synthetic cathinone analogs related to the widely abused compound MDPV, a common constituent in "bath salts" possessing potent actions at the dopamine transporter. PMID- 27677787 TI - In Situ Observation of Single-Molecule Surface Reactions from Low to High Affinities. AB - In situ observation of single-molecule surface reactions from low to high affinities is achieved by resonant coupling between optical whispering-gallery modes and the localized surface plasmon of nanorods. Transient and permanent interactions between ligands (thiol, amine) and the gold surface are monitored without labels, allowing direct determination of the associated kinetic constants and rapid development of new functionalization protocols. PMID- 27677786 TI - Community-based real-world treatment outcomes of sofosbuvir/ledipasvir in Asians with chronic hepatitis C virus genotype 6 in the United States. AB - Sofosbuvir/ledipasvir (SOF/LDV) is the first all-oral ribavirin-free treatment approved for chronic hepatitis C virus (HCV) genotype 6, offering a safe and highly efficacious treatment option. Large studies evaluating real-world outcomes of this regimen are lacking. We aim to evaluate real-world treatment outcomes for HCV genotype 6. A retrospective cohort study evaluated 65 adults (age >=18) with chronic HCV genotype 6 treated with SOF/LDV without ribavirin at a community gastroenterology clinic in the United States from November 2014 to May 2016. Rates of undetectable virus at week 4 on treatment, at end of treatment (EOT) and SVR12 were stratified by the presence of cirrhosis and prior treatment (treatment naive vs treatment experienced). Among 65 patients with chronic HCV genotype 6 treated with SOF/LDV (52.3% male, mean age 66.3 years [SD 9.7], 41.5% cirrhosis and 15.4% treatment experienced), 97.3% had undetectable virus at week 4 on treatment, 96.9% had undetectable virus at EOT and 95.3% achieved SVR12. SVR12 was 100% in females vs 91.2% in males, P=.096, and 92.3% in patients with cirrhosis vs 97.4% in those without cirrhosis, P=.347. Resistance testing of treatment failures was attempted but unsuccessful due to lack of conforming primers to define the possible resistance mutations. Among the largest U.S. community-based real-world cohort of Asian chronic HCV genotype 6 patients treated with all-oral SOF/LDV without ribavirin, SVR12 was similar to SVR12 reported in clinical trials, confirming the safety and effectiveness of this regimen and validating current HCV genotype 6 treatment guideline recommendations. PMID- 27677785 TI - Complement C3 inhibitor Cp40 attenuates xenoreactions in pig hearts perfused with human blood. AB - BACKGROUND: The complement system plays a crucial role in acute xenogeneic reactions after cardiac transplantation. We used an ex vivo perfusion model to investigate the effect of Cp40, a compstatin analog and potent inhibitor of complement at the level of C3. METHODS: Fifteen wild-type pig hearts were explanted, cardiopleged, and reperfused ex vivo after 150 minutes of cold ischemia. Hearts were challenged in a biventricular working heart mode to evaluate cardiac perfusion and function. In the treatment group (n=5), the complement cascade was blocked at the level of C3 using Cp40, using diluted human blood. Untreated human and porcine blood was used for controls. RESULTS: Throughout the perfusion, C3 activation was inhibited when Cp40 was used (mean of all time points: 1.11 +/- 0.34% vs 3.12 +/- 0.48% control activation; P<.01). Compared to xenoperfused controls, the cardiac index improved significantly in the treated group (6.5 +/- 4.2 vs 3.5 +/- 4.8 mL/min/g; P=.03, 180 minutes perfusion), while the concentration of lactate dehydrogenase as a maker for cell degradation was reduced in the perfusate (583 +/- 187 U/mL vs 2108 +/- 1145 U/mL, P=.02). Histological examination revealed less hemorrhage and edema, and immunohistochemistry confirmed less complement fragment deposition than in untreated xenoperfused controls. CONCLUSIONS: Cp40 efficiently prevents C3 activation of the complement system, resulting in reduced cell damage and preserved function in wild-type porcine hearts xenoperfused ex vivo. We suggest that this compstatin analog, which blocks all main pathways of complement activation, could be a beneficial perioperative treatment in preclinical and in future clinical xenotransplantation. PMID- 27677788 TI - Exposing the Three-Dimensional Biogeography and Metabolic States of Pathogens in Cystic Fibrosis Sputum via Hydrogel Embedding, Clearing, and rRNA Labeling. AB - : Physiological resistance to antibiotics confounds the treatment of many chronic bacterial infections, motivating researchers to identify novel therapeutic approaches. To do this effectively, an understanding of how microbes survive in vivo is needed. Though much can be inferred from bulk approaches to characterizing complex environments, essential information can be lost if spatial organization is not preserved. Here, we introduce a tissue-clearing technique, termed MiPACT, designed to retain and visualize bacteria with associated proteins and nucleic acids in situ on various spatial scales. By coupling MiPACT with hybridization chain reaction (HCR) to detect rRNA in sputum samples from cystic fibrosis (CF) patients, we demonstrate its ability to survey thousands of bacteria (or bacterial aggregates) over millimeter scales and quantify aggregation of individual species in polymicrobial communities. By analyzing aggregation patterns of four prominent CF pathogens, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus sp., and Achromobacter xylosoxidans, we demonstrate a spectrum of aggregation states: from mostly single cells (A. xylosoxidans), to medium-sized clusters (S. aureus), to a mixture of single cells and large aggregates (P. aeruginosa and Streptococcus sp.). Furthermore, MiPACT HCR revealed an intimate interaction between Streptococcus sp. and specific host cells. Lastly, by comparing standard rRNA fluorescence in situ hybridization signals to those from HCR, we found that different populations of S. aureus and A. xylosoxidans grow slowly overall yet exhibit growth rate heterogeneity over hundreds of microns. These results demonstrate the utility of MiPACT-HCR to directly capture the spatial organization and metabolic activity of bacteria in complex systems, such as human sputum. IMPORTANCE: The advent of metagenomic and metatranscriptomic analyses has improved our understanding of microbial communities by empowering us to identify bacteria, calculate their abundance, and profile gene expression patterns in complex environments. We are still technologically limited, however, in regards to the many questions that bulk measurements cannot answer, specifically in assessing the spatial organization of microbe-microbe and microbe-host interactions. Here, we demonstrate the power of an enhanced optical clearing method, MiPACT, to survey important aspects of bacterial physiology (aggregation, host interactions, and growth rate), in situ, with preserved spatial information when coupled to rRNA detection by HCR. Our application of MiPACT-HCR to cystic fibrosis patient sputum revealed species specific aggregation patterns, yet slow growth characterized the vast majority of bacterial cells regardless of their cell type. More broadly, MiPACT, coupled with fluorescent labeling, promises to advance the direct study of microbial communities in diverse environments, including microbial habitats within mammalian systems. PMID- 27677789 TI - Annual Removal of Aboveground Plant Biomass Alters Soil Microbial Responses to Warming. AB - : Clipping (i.e., harvesting aboveground plant biomass) is common in agriculture and for bioenergy production. However, microbial responses to clipping in the context of climate warming are poorly understood. We investigated the interactive effects of grassland warming and clipping on soil properties and plant and microbial communities, in particular, on microbial functional genes. Clipping alone did not change the plant biomass production, but warming and clipping combined increased the C4 peak biomass by 47% and belowground net primary production by 110%. Clipping alone and in combination with warming decreased the soil carbon input from litter by 81% and 75%, respectively. With less carbon input, the abundances of genes involved in degrading relatively recalcitrant carbon increased by 38% to 137% in response to either clipping or the combined treatment, which could weaken long-term soil carbon stability and trigger positive feedback with respect to warming. Clipping alone also increased the abundance of genes for nitrogen fixation, mineralization, and denitrification by 32% to 39%. Such potentially stimulated nitrogen fixation could help compensate for the 20% decline in soil ammonium levels caused by clipping alone and could contribute to unchanged plant biomass levels. Moreover, clipping tended to interact antagonistically with warming, especially with respect to effects on nitrogen cycling genes, demonstrating that single-factor studies cannot predict multifactorial changes. These results revealed that clipping alone or in combination with warming altered soil and plant properties as well as the abundance and structure of soil microbial functional genes. Aboveground biomass removal for biofuel production needs to be reconsidered, as the long-term soil carbon stability may be weakened. IMPORTANCE: Global change involves simultaneous alterations, including those caused by climate warming and land management practices (e.g., clipping). Data on the interactive effects of warming and clipping on ecosystems remain elusive, particularly in microbial ecology. This study found that clipping alters microbial responses to warming and demonstrated the effects of antagonistic interactions between clipping and warming on microbial functional genes. Clipping alone or combined with warming enriched genes degrading relatively recalcitrant carbon, likely reflecting the decreased quantity of soil carbon input from litter, which could weaken long-term soil C stability and trigger positive warming feedback. These results have important implications in assessing and predicting the consequences of global climate change and indicate that the removal of aboveground biomass for biofuel production may need to be reconsidered. PMID- 27677790 TI - Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule. AB - : Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. IMPORTANCE: The capsule determines >90 different pneumococcal serotypes, which vary in capsule size, virulence, duration, and prevalence of carriage. Current serotype-specific vaccines elicit anticapsule antibodies. Pneumococcus can take up exogenous DNA by transformation and insert it into its chromosome by homologous recombination. This mechanism has disseminated drug resistance and generated vaccine escape variants. It is hence crucial to pneumococcal evolutionary response to interventions, but there has been no systematic study quantifying whether serotypes vary in recombination and whether this is associated with serotype-specific properties such as capsule size or carriage duration. Larger capsules could physically inhibit DNA uptake, or given the longer carriage duration for larger capsules, this may promote recombination. We find that recombination varies among capsules and is associated with capsule size, carriage duration, and carriage prevalence and negatively associated with invasiveness. The consequence of this work is that serotypes with different capsules may respond differently to selective pressures like vaccines. PMID- 27677793 TI - Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules. AB - The Gram-negative outer membrane is an important barrier that provides protection against toxic compounds, which include antibiotics and host innate immune molecules such as cationic antimicrobial peptides. Recently, significant research progress has been made in understanding the biogenesis, regulation, and functioning of the outer membrane, including a recent paper from the laboratory of Dr. Brett Finlay at the University of British Columbia (J. van der Heijden et al., mBio 7:e01238-16, 2016, http://dx.doi.org/10.1128/mBio.01541-16). These investigators demonstrate that toxic oxygen radicals, such as those found in host tissues, regulate outer membrane permeability by altering the outer membrane porin protein channels to regulate the influx of oxygen radicals as well as beta lactam antibiotics. This commentary provides context about this interesting paper and discusses the prospects of utilizing increased knowledge of outer membrane biology to develop new antibiotics for antibiotic-resistant Gram-negative bacteria. PMID- 27677792 TI - Chlamydial Protease-Like Activity Factor and Type III Secreted Effectors Cooperate in Inhibition of p65 Nuclear Translocation. AB - : The chlamydial protease-like activity factor (CPAF) is hypothesized to be an important secreted virulence factor; however, challenges in denaturing its proteolytic activity have hampered attempts to identify its legitimate targets. Here, we use a genetic and proteomic approach to identify authentic CPAF targets. Human epithelial cells infected with CPAF-sufficient and CPAF-deficient chlamydiae were lysed using known CPAF-denaturing conditions. Their protein profiles were analyzed using isobaric mass tags and liquid chromatography-tandem mass spectrometry. Comparative analysis of CPAF-sufficient and CPAF-deficient infections identified a limited number of CPAF host and chlamydial protein targets. Host targets were primarily interferon-stimulated gene products, whereas chlamydial targets were type III secreted proteins. We provide evidence supporting a cooperative role for CPAF and type III secreted effectors in blocking NF-kappaB p65 nuclear translocation, resulting in decreased beta interferon and proinflammatory cytokine synthesis. Genetic complementation of null organisms with CPAF restored p65 nuclear translocation inhibition and proteolysis of chlamydial type III secreted effector proteins (T3SEs). We propose that CPAF and T3SEs cooperate in the inhibition of host innate immunity. IMPORTANCE: Chlamydia trachomatis is an important human pathogen responsible for over 100 million infections each year worldwide. Its success as an intracellular pathogen revolves around its ability to evade host immunity. The chlamydial protease-like activity factor (CPAF) is a conserved serine protease secreted into the host cytosol of infected cells that is thought to play an important role in immune evasion. Currently, CPAF's authentic in situ target(s) and mechanism of action in immune evasion are poorly characterized. Using a CPAF-deficient strain and high-throughput proteomics, we report novel CPAF host and chlamydial targets. Host targets were primarily interferon-stimulated genes, whereas chlamydial targets were exclusively type III secreted proteins. We propose a novel mechanism for CPAF and type III secreted proteins in the evasion of host innate immune responses. These findings provide new insights into CPAF's function as a virulence factor and a better understanding of how chlamydiae evade host immunity. PMID- 27677794 TI - The Underestimation of Global Microbial Diversity. PMID- 27677791 TI - CAG Expansions Are Genetically Stable and Form Nontoxic Aggregates in Cells Lacking Endogenous Polyglutamine Proteins. AB - : Proteins containing polyglutamine (polyQ) regions are found in almost all eukaryotes, albeit with various frequencies. In humans, proteins such as huntingtin (Htt) with abnormally expanded polyQ regions cause neurodegenerative diseases such as Huntington's disease (HD). To study how the presence of endogenous polyQ aggregation modulates polyQ aggregation and toxicity, we expressed polyQ expanded Htt fragments (polyQ Htt) in Schizosaccharomyces pombe In stark contrast to other unicellular fungi, such as Saccharomyces cerevisiae, S. pombe is uniquely devoid of proteins with more than 10 Q repeats. We found that polyQ Htt forms aggregates within S. pombe cells only with exceedingly long polyQ expansions. Surprisingly, despite the presence of polyQ Htt aggregates in both the cytoplasm and nucleus, no significant growth defect was observed in S. pombe cells. Further, PCR analysis showed that the repetitive polyQ-encoding DNA region remained constant following transformation and after multiple divisions in S. pombe, in contrast to the genetic instability of polyQ DNA sequences in other organisms. These results demonstrate that cells with a low content of polyQ or other aggregation-prone proteins can show a striking resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the evolutionary emergence and exclusion of polyQ expansion proteins in different organisms. IMPORTANCE: Polyglutamine (polyQ) proteins encoded by repetitive CAG DNA sequences serve a variety of normal biological functions. Yet some proteins with abnormally expanded polyQ regions cause neurodegeneration through unknown mechanisms. To study how distinct cellular environments modulate polyQ aggregation and toxicity, we expressed CAG expanded huntingtin fragments in Schizosaccharomyces pombe In stark contrast to many other eukaryotes, S. pombe is uniquely devoid of proteins containing long polyQ tracts. Our results show that S. pombe cells, despite their low content of endogenous polyQ proteins, exhibit striking and unexpected resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the emergence and expansion of polyQ domains in eukaryotic evolution. PMID- 27677795 TI - Acinetobacter baumannii Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation. AB - : During infection, bacterial pathogens must adapt to a nutrient metal-limited environment that is imposed by the host. The innate immune protein calprotectin inhibits bacterial growth in vitro by chelating the divalent metal ions zinc (Zn2+, Zn) and manganese (Mn2+, Mn), but pathogenic bacteria are able to cause disease in the presence of this antimicrobial protein in vivo. One such pathogen is Acinetobacter baumannii, a Gram-negative bacterium that causes pneumonia and bloodstream infections that can be complicated by resistance to multiple antibiotics. A. baumannii inhibition by calprotectin is dependent on calprotectin Mn binding, but the mechanisms employed by A. baumannii to overcome Mn limitation have not been identified. This work demonstrates that A. baumannii coordinates transcription of an NRAMP family Mn transporter and a urea carboxylase to resist the antimicrobial activities of calprotectin. This NRAMP family transporter facilitates Mn accumulation and growth of A. baumannii in the presence of calprotectin. A. baumannii is found to utilize urea as a sole nitrogen source, and urea utilization requires the urea carboxylase encoded in an operon with the NRAMP family transporter. Moreover, urea carboxylase activity is essential for calprotectin resistance in A. baumannii Finally, evidence is provided that this system combats calprotectin in vivo, as deletion of the transporter impairs A. baumannii fitness in a mouse model of pneumonia, and this fitness defect is modulated by the presence of calprotectin. These findings reveal that A. baumannii has evolved mechanisms to subvert host-mediated metal sequestration and they uncover a connection between metal starvation and metabolic stress. IMPORTANCE: Acinetobacter baumannii is a bacterium that causes bloodstream, wound, urinary tract, and pneumonia infections, with a high disease burden in intensive care units. Treatment of A. baumannii infection is complicated by resistance to most antibiotics in use today, and resistance to last-resort therapies has become commonplace. New treatments for A. baumannii infection are desperately needed, but our current understanding of the bacterial factors required to cause infection is limited. We previously found that the abundant innate immune protein calprotectin inhibits the growth of A. baumannii by withholding essential metals. Despite this, A. baumannii is still able to infect wild-type mice, which produce calprotectin during infection. Here, we identify factors employed by A. baumannii during infection to overcome calprotectin mediated metal sequestration. Moreover, we expose a connection between metal starvation and metabolism that may be a "chink in the armor" of A. baumannii and lead to new treatment options. PMID- 27677797 TI - Reply to "The Underestimation of Global Microbial Diversity". PMID- 27677796 TI - A Bacillus anthracis Genome Sequence from the Sverdlovsk 1979 Autopsy Specimens. AB - : Anthrax is a zoonotic disease that occurs naturally in wild and domestic animals but has been used by both state-sponsored programs and terrorists as a biological weapon. A Soviet industrial production facility in Sverdlovsk, USSR, proved deficient in 1979 when a plume of spores was accidentally released and resulted in one of the largest known human anthrax outbreaks. In order to understand this outbreak and others, we generated a Bacillus anthracis population genetic database based upon whole-genome analysis to identify all single nucleotide polymorphisms (SNPs) across a reference genome. Phylogenetic analysis has defined three major clades (A, B, and C), B and C being relatively rare compared to A. The A clade has numerous subclades, including a major polytomy named the trans-Eurasian (TEA) group. The TEA radiation is a dominant evolutionary feature of B. anthracis, with many contemporary populations having resulted from a large spatial dispersal of spores from a single source. Two autopsy specimens from the Sverdlovsk outbreak were deep sequenced to produce draft B. anthracis genomes. This allowed the phylogenetic placement of the Sverdlovsk strain into a clade with two Asian live vaccine strains, including the Russian Tsiankovskii strain. The genome was examined for evidence of drug resistance manipulation or other genetic engineering, but none was found. The Soviet Sverdlovsk strain genome is consistent with a wild-type strain from Russia that had no evidence of genetic manipulation during its industrial production. This work provides insights into the world's largest biological weapons program and provides an extensive B. anthracis phylogenetic reference. IMPORTANCE: The 1979 Russian anthrax outbreak resulted from an industrial accident at the Soviet anthrax spore production facility in the city of Sverdlovsk. Deep genomic sequencing of two autopsy specimens generated a draft genome and phylogenetic placement of the Soviet Sverdlovsk anthrax strain. While it is known that Soviet scientists had genetically manipulated Bacillus anthracis with the potential to evade vaccine prophylaxis and antibiotic therapeutics, there was no genomic evidence of this from the Sverdlovsk production strain genome. The whole-genome SNP genotype of the Sverdlovsk strain was used to precisely identify it and its close relatives in the context of an extensive global B. anthracis strain collection. This genomic identity can now be used for forensic tracking of this weapons material on a global scale and for future anthrax investigations. PMID- 27677799 TI - Secondary Release of Exosomes From Astrocytes Contributes to the Increase in Neural Plasticity and Improvement of Functional Recovery After Stroke in Rats Treated With Exosomes Harvested From MicroRNA 133b-Overexpressing Multipotent Mesenchymal Stromal Cells. AB - We previously demonstrated that multipotent mesenchymal stromal cells (MSCs) that overexpress microRNA 133b (miR-133b) significantly improve functional recovery in rats subjected to middle cerebral artery occlusion (MCAO) compared with naive MSCs and that exosomes generated from naive MSCs mediate the therapeutic benefits of MSC therapy for stroke. Here we investigated whether exosomes isolated from miR-133b-overexpressing MSCs (Ex-miR-133b+) exert amplified therapeutic effects. Rats subjected to 2 h of MCAO were intra-arterially injected with Ex-miR-133b+, exosomes from MSCs infected by blank vector (Ex-Con), or phosphate-buffered saline (PBS) and were sacrificed 28 days after MCAO. Compared with the PBS treatment, both exosome treatment groups exhibited significant improvement of functional recovery. Ex-miR-133b+ treatment significantly increased functional improvement and neurite remodeling/brain plasticity in the ischemic boundary area compared with the Ex-Con treatment. Treatment with Ex-miR-133b+ also significantly increased brain exosome content compared with Ex-Con treatment. To elucidate mechanisms underlying the enhanced therapeutic effects of Ex-miR-133b+, astrocytes cultured under oxygen- and glucose-deprived (OGD) conditions were incubated with exosomes harvested from naive MSCs (Ex-Naive), miR-133b downregulated MSCs (Ex-miR-133b-), and Ex-miR-133b+. Compared with the Ex-Naive treatment, Ex-miR-133b+ significantly increased exosomes released by OGD astrocytes, whereas Ex-miR-133b- significantly decreased the release. Also, exosomes harvested from OGD astrocytes treated with Ex-miR-133b+ significantly increased neurite branching and elongation of cultured cortical embryonic rat neurons compared with the exosomes from OGD astrocytes subjected to Ex-Con. Our data suggest that exosomes harvested from miR-133b-overexpressing MSCs improve neural plasticity and functional recovery after stroke with a contribution from a stimulated secondary release of neurite-promoting exosomes from astrocytes. PMID- 27677800 TI - Cytomixis in tobacco microsporogenesis: are there any genome parts predisposed to migration? AB - Cytomixis is a poorly studied process of nuclear migration between plant cells, discovered in microsporogenesis of several hundreds of plant species. The chromosomes that migrate between tobacco microsporocytes have been for the first time identified using fluorescence in situ hybridization (FISH), and the question whether cytomixis is a random or a targeted process is answered. The distribution of four repetitive sequences used for identifying the tobacco chromosomes-NTRS, 5S rDNA, GRS, and HSR60-has been examined in the migrating chromatin, and the micronuclei formed after cytomixis. The distribution of tobacco S and T genomes has been analyzed in the cytomictic chromatin using genomic in situ hybridization (GISH). As has been shown (chi 2 test), the labeled DNA probes marking the listed sequences in tobacco genome are observed in the micronuclei formed after cytomixis with the probability not exceeding the theoretically expected value if cytomixis considered as a random process. Thus, it is shown that cytomixis is not a targeted process, and the chromosomes migrate between microsporocytes in a random manner. PMID- 27677801 TI - Versatility of the green microalga cell vacuole function as revealed by analytical transmission electron microscopy. AB - Vacuole is a multifunctional compartment central to a large number of functions (storage, catabolism, maintenance of the cell homeostasis) in oxygenic phototrophs including microalgae. Still, microalgal cell vacuole is much less studied than that of higher plants although knowledge of the vacuolar structure and function is essential for understanding physiology of nutrition and stress tolerance of microalgae. Here, we combined the advanced analytical and conventional transmission electron microscopy methods to obtain semi quantitative, spatially resolved at the subcellular level information on elemental composition of the cell vacuoles in several free-living and symbiotic chlorophytes. We obtained a detailed record of the changes in cell and vacuolar ultrastructure in response to environmental stimuli under diverse conditions. We suggested that the vacuolar inclusions could be divided into responsible for storage of phosphorus (mainly in form of polyphosphate) and those accommodating non-protein nitrogen (presumably polyamine) reserves, respectively.The ultrastructural findings, together with the data on elemental composition of different cell compartments, allowed us to speculate on the role of the vacuolar membrane in the biosynthesis and sequestration of polyphosphate. We also describe the ultrastructural evidence of possible involvement of the tonoplast in the membrane lipid turnover and exchange of energy and metabolites between chloroplasts and mitochondria. These processes might play a significant role in acclimation in different stresses including nitrogen starvation and extremely high level of CO2 and might also be of importance for microalgal biotechnology. Advantages and limitations of application of analytical electron microscopy to biosamples such as microalgal cells are discussed. PMID- 27677802 TI - The structure of the desiccated Richtersius coronifer (Richters, 1903). AB - Tun formation is an essential morphological adaptation for entering the anhydrobiotic state in tardigrades, but its internal structure has rarely been investigated. We present the structure and ultrastructure of organs and cells in desiccated Richtersius coronifer by transmission and scanning electron microscopy, confocal microscopy, and histochemical methods. A 3D reconstruction of the body organization of the tun stage is also presented. The tun formation during anhydrobiosis of tardigrades is a process of anterior-posterior body contraction, which relocates some organs such as the pharyngeal bulb. The cuticle is composed of epicuticle, intracuticle and procuticle; flocculent coat; and trilaminate layer. Moulting does not seem to restrict the tun formation, as evidenced from tardigrade tuns that were in the process of moulting. The storage cells of desiccated specimens filled up the free inner space and surrounded internal organs, such as the ovary and digestive system, which were contracted. All cells (epidermal cells, storage cells, ovary cells, cells of the digestive system) underwent shrinkage, and their cytoplasm was electron dense. Lipids and polysaccharides dominated among reserve material of storage cells, while the amount of protein was small. The basic morphology of specific cell types and organelles did not differ between active and anhydrobiotic R. coronifer. PMID- 27677803 TI - Novel perspectives on diagnosis and clinical significance of the post-thrombotic syndrome in children. AB - INTRODUCTION: Given the increase in venous thromboembolic events (VTE) in children, the incidence, diagnosis and management of post thrombotic syndrome (PTS) in children is of increasing interest. Current challenges facing clinicians caring for children with VTE is the limited evidence of the long-term outcomes for this cohort; specifically the significance and potential functional impairment associated with PTS. AREAS COVERED: This paper reviews the current evidence to elucidate the risk factors for PTS in children, methods for diagnosis and management of PTS in children (aged less than 18 years). Medline, Cinahl and PsycINFO database searches were undertaken using key search terms. Priority areas in need of further research are highlighted. Expert commentary: The two paediatric PTS assessment tools currently in use have been acknowledged to overcall the incidence of mild PTS in children. A PTS tool's ability to distinguish between clinically significant PTS and mild PTS is crucial. Variation in how PTS has been reported in children across the literature suggests that the real incidence of moderate and /or clinically significant PTS in children is unknown. Furthermore, evidence is lacking about the functional impairment experienced by children with clinically significant PTS and what this means for their long-term health. PMID- 27677805 TI - Commentary: Periodontal Treatment and Inflammation in Diabetes: Association or Causation? AB - The causal effect of periodontal treatment on systemic outcomes is unclear because even randomized controlled trials (RCTs) have conflicting results. Two models are proposed to explain the apparently conflicting findings from RCTs evaluating the effect of periodontal treatment on inflammation and systemic outcomes among individuals with type 2 diabetes. PMID- 27677806 TI - Letter to the Editor: Re: Alcohol Consumption and Periodontitis: Quantification of Periodontal Pathogens and Cytokines. PMID- 27677804 TI - Novel mechanism of modulation at a ligand-gated ion channel; action of 5-Cl indole at the 5-HT3 A receptor. AB - BACKGROUND AND PURPOSE: The 5-HT3 receptor is a prototypical member of the Cys loop ligand-gated ion channel (LGIC) superfamily and an established therapeutic target. In addition to activation via the orthosteric site, receptor function can be modulated by allosteric ligands. We have investigated the pharmacological action of Cl-indole upon the 5-HT3 A receptor and identified that this positive allosteric modulator possesses a novel mechanism of action for LGICs. EXPERIMENTAL APPROACH: The impact of Cl-indole upon the 5-HT3 receptor was assessed using single cell electrophysiological recordings and [3 H]-granisetron binding in HEK293 cells stably expressing the 5-HT3 receptor. KEY RESULTS: Cl indole failed to evoke 5-HT3 A receptor-mediated responses (up to 30 MUM) or display affinity for the [3 H]-granisetron binding site. However, in the presence of Cl-indole, termination of 5-HT application revealed tail currents mediated via the 5-HT3 A receptor that were independent of the preceding 5-HT concentration but were antagonized by the 5-HT3 receptor antagonist, ondansetron. These tail currents were absent in the 5-HT3 AB receptor. Furthermore, the presence of 5-HT revealed a concentration-dependent increase in the affinity of Cl-indole for the orthosteric binding site of the human 5-HT3 A receptor. CONCLUSIONS AND IMPLICATIONS: Cl-indole acts as both an orthosteric agonist and an allosteric modulator, but the presence of an orthosteric agonist (e.g. 5-HT) is a prerequisite to reveal both actions. Precedent for ago-allosteric action is available, yet the essential additional presence of an orthosteric agonist is now reported for the first time. This widening of the pharmacological mechanisms to modulate LGICs may offer further therapeutic opportunities. PMID- 27677807 TI - Letter to the Editor: Authors' Response. PMID- 27677809 TI - Letter to the Editor: Authors' Response. PMID- 27677808 TI - Letter to the Editor: Re: Long-Term Results Comparing Xenogeneic Collagen Matrix and Autogenous Connective Tissue Grafts With Coronally Advanced Flaps for Treatment of Dehiscence-Type Recession Defects. PMID- 27677810 TI - Gingival Margin Stability After Mucogingival Plastic Surgery. The Effect of Manual Versus Powered Toothbrushing: A Randomized Clinical Trial. AB - BACKGROUND: Oscillating-rotating power toothbrushes have been proven to be clinically efficacious. To the best of the authors' knowledge, a clinical evaluation of the safety of these toothbrushes after surgical root coverage procedures has not been published. The aim of this study is to evaluate the gingival margin (GM) stability with the use of an oscillating-rotating toothbrush compared with a manual toothbrush. METHODS: Sixty healthy individuals with at least one Miller Class I or II gingival recession underwent a surgical root coverage procedure. Soft-bristle manual and powered toothbrushes were given to participants randomly assigned to control and test groups, respectively. Full mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depth (PD), and recession depth (RD) were recorded at baseline and 1, 3, and 6 months after completion of the surgical procedure. Data analyses were performed using linear random-intercept models to take into account within-participant correlations over time. Temporal trend differences across treatments by including treatment-time interaction terms were then tested using a global Wald test. RESULTS: Use of a powered toothbrush resulted in a significantly greater reduction of recorded periodontal clinical indices compared with a manual device (FMPS, P = 0.05; FMBS, P = 0.005; RD, P = 0.004). No significant differences were noticed between the two experimental groups both for PD (P = 0.03) and clinical attachment level (P = 0.11). Complete root coverage was significantly higher in participants who used the powered toothbrush compared with the manual toothbrush at 6 months (control, 66.67%; test, 96.67%; P = 0.002). CONCLUSION: Use of an oscillating-rotating powered toothbrush with a soft-bristle head resulted in higher GM stability after root coverage procedures compared with the use of a manual soft-bristled toothbrush. PMID- 27677811 TI - Assessing the Risk of Hospital-Acquired Clostridium Difficile Infection With Proton Pump Inhibitor Use: A Meta-Analysis. AB - BACKGROUND Clostridium difficile is the principal infectious cause of antibiotic associated diarrhea and accounts for 12% of hospital-acquired infections. Recent literature has shown an increased risk of C. difficile infection (CDI) with proton pump inhibitor (PPI) use. OBJECTIVE To conduct a systematic assessment of the risk of hospital-acquired CDI following exposure to PPI. METHODS We searched multiple databases for studies examining the relationship between PPI and hospital-acquired CDI. Pooled odds ratios were generated and assessment for heterogeneity performed. RESULTS We found 23 observational studies involving 186,033 cases that met eligibility criteria. Across studies, 10,307 cases of hospital-acquired CDI were reported. Significant heterogeneity was present; therefore, a random effects model was used. The pooled odds ratio was 1.81 (95% CI, 1.52-2.14), favoring higher risk of CDI with PPI use. Significant heterogeneity was present, likely due to differences in assessment of exposure, study population, and definition of CDI. DISCUSSION This meta-analysis suggests PPIs significantly increase the risk of hospital-acquired CDI. Given the significant health and economic burden of CDI and the risks of PPI, optimization of PPI use should be included in a multifaceted approach to CDI prevention. Infect Control Hosp Epidemiol 2016;1408-1417. PMID- 27677813 TI - Climate change is projected to outpace rates of niche change in grasses. AB - Climate change may soon threaten much of global biodiversity, especially if species cannot adapt to changing climatic conditions quickly enough. A critical question is how quickly climatic niches change, and if this speed is sufficient to prevent extinction as climates warm. Here, we address this question in the grass family (Poaceae). Grasses are fundamental to one of Earth's most widespread biomes (grasslands), and provide roughly half of all calories consumed by humans (including wheat, rice, corn and sorghum). We estimate rates of climatic niche change in 236 species and compare these with rates of projected climate change by 2070. Our results show that projected climate change is consistently faster than rates of niche change in grasses, typically by more than 5000-fold for temperature-related variables. Although these results do not show directly what will happen under global warming, they have troubling implications for a major biome and for human food resources. PMID- 27677812 TI - Is there a trade-off between peak performance and performance breadth across temperatures for aerobic scope in teleost fishes? AB - The physiology and behaviour of ectotherms are strongly influenced by environmental temperature. A general hypothesis is that for performance traits, such as those related to growth, metabolism or locomotion, species face a trade off between being a thermal specialist or a thermal generalist, implying a negative correlation between peak performance and performance breadth across a range of temperatures. Focusing on teleost fishes, we performed a phylogenetically informed comparative analysis of the relationship between performance peak and breadth for aerobic scope (AS), which represents whole animal capacity available to carry out simultaneous oxygen-demanding processes (e.g. growth, locomotion, reproduction) above maintenance. Literature data for 28 species indicate that peak aerobic capacity is not linked to thermal performance breadth and that other physiological factors affecting thermal tolerance may prevent such a trade-off from emerging. The results therefore suggest that functional links between peak and thermal breadth for AS may not constrain evolutionary responses to environmental changes such as climate warming. PMID- 27677814 TI - Food limitation constrains host immune responses to nematode infections. AB - Trade-offs in the allocation of finite-energy resources among immunological defences and other physiological processes are believed to influence infection risk and disease severity in food-limited wildlife populations. However, this prediction has received little experimental investigation. Here we test the hypothesis that food limitation impairs the ability of wild field voles (Microtus agrestis) to mount an immune response against parasite infections. We conducted a replicated experiment on vole populations maintained in large outdoor enclosures during boreal winter, using food supplementation and anthelmintic treatment of intestinal nematodes. Innate immune responses against intestinal parasite infections were compared between food-supplemented and non-supplemented voles. Voles with high food availability mounted stronger immune responses against intestinal nematode infections than food-limited voles. No food effects were seen in immune responses to intracellular coccidian parasites, possibly owing to their ability to avoid activation of innate immune pathways. Our findings demonstrate that food availability constrains vole immune responses against nematode infections, and support the concept that spatio-temporal heterogeneity in food availability creates variation in infectious disease susceptibility. PMID- 27677815 TI - Mimics here and there, but not everywhere: Mullerian mimicry in Ceroglossus ground beetles? AB - The ground beetle genus Ceroglossus contains co-distributed species that show pronounced intraspecific diversity in the form of geographical colour morphs. While colour morphs among different species appear to match in some geographical regions, in others, there is little apparent colour matching. Mimicry is a potential explanation for covariation in colour patterns, but it is not clear whether the degree of sympatric colour matching is higher than expected by chance given the obvious mismatches among morphs in some regions. Here, we used reflectance spectrometry to quantify elytral coloration from the perspective of an avian predator to test whether colour similarity between species is, indeed, higher in sympatry. After finding no significant phylogenetic signal in the colour data, analyses showed strong statistical support for sympatric colour similarity between species despite the apparent lack of colour matching in some areas. We hypothesize Mullerian mimicry as the responsible mechanism for sympatric colour similarity in Ceroglossus and discuss potential explanations and future directions to elucidate why mimicry has not developed similar levels of interspecific colour resemblance across space. PMID- 27677816 TI - Onychophoran-like musculature in a phosphatized Cambrian lobopodian. AB - The restricted, exclusively terrestrial distribution of modern Onychophora contrasts strikingly with the rich diversity of onychophoran-like fossils preserved in marine Cambrian Lagerstatten The transition from these early forebears to the modern onychophoran body plan is poorly constrained, in part owing to the absence of fossils preserving details of the soft anatomy. Here, we report muscle tissue in a new early Cambrian (Stage 3) lobopodian, Tritonychus phanerosarkus gen. et sp. nov., preserved in the Orsten fashion by three dimensional replication in phosphate. This first report of Palaeozoic onychophoran musculature establishes peripheral musculature as a characteristic of the ancestral panarthropod, but documents an unexpected muscular configuration. Phylogenetic analysis reconstructs T. phanerosarkus as one of a few members of the main onychophoran lineage-which was as rare and as cryptic in the Cambrian period as it is today. PMID- 27677817 TI - Predicting range-shift success potential for tropical marine fishes using external morphology. AB - With global change accelerating the rate of species' range shifts, predicting which are most likely to establish viable populations in their new habitats is key to understanding how biological systems will respond. Annually, in Australia, tropical fish larvae from the Great Barrier Reef (GBR) are transported south via the East Australian Current (EAC), settling into temperate coastal habitats for the summer period, before experiencing near-100% mortality in winter. However, within 10 years, predicted winter ocean temperatures for the southeast coast of Australia will remain high enough for more of these so-called 'tropical vagrants' to survive over winter. We used a method of morphological niche analysis, previously shown to be an effective predictor of invasion success by fishes, to project which vagrants have the greatest likelihood of undergoing successful range shifts under these new climatic conditions. We find that species from the family of butterflyfishes (Chaetodontidae), and the moorish idol, Zanclus cornutus, are most likely to be able to exploit new niches within the ecosystem once physiological barriers to overwintering by tropical vagrant species are removed. Overall, the position of vagrants within the morphospace was strongly skewed, suggesting that impending competitive pressures may impact disproportionately on particular parts of the native community. PMID- 27677818 TI - Is the enhanced dispersal rate seen at invasion fronts a behaviourally plastic response to encountering novel ecological conditions? AB - As a population expands into novel areas (as occurs in biological invasions), the range edge becomes dominated by rapidly dispersing individuals-thereby accelerating the rate of population spread. That acceleration has been attributed to evolutionary processes (natural selection and spatial sorting), to which we add a third complementary process: behavioural plasticity. Encountering environmental novelty may directly elicit an increased rate of dispersal. When we reciprocally translocated cane toads (Rhinella marina) among study sites in southern Australia, the transported animals massively increased dispersal rates relative to residents (to an extent similar to the evolved increase between range core versus invasion-front toad populations in Australia). The responses of these translocated toads show that even range-core toads are capable of the long distance dispersal rates of invasion-front conspecifics and suggest that rapid dispersal (rather than evolving de novo) has simply been expanded from facultative to constitutive expression. PMID- 27677819 TI - Hidden diversity of Acoelomorpha revealed through metabarcoding. AB - Animals with bilateral symmetry comprise the majority of the described species within Metazoa. However, the nature of the first bilaterian animal remains unknown. As most recent molecular phylogenies point to Xenacoelomorpha as the sister group to the rest of Bilateria, understanding their biology, ecology and diversity is key to reconstructing the nature of the last common bilaterian ancestor (Urbilateria). To date, sampling efforts have focused mainly on coastal areas, leaving potential gaps in our understanding of the full diversity of xenacoelomorphs. We therefore analysed 18S rDNA metabarcoding data from three marine projects covering benthic and pelagic habitats worldwide. Our results show that acoels have a greater richness in planktonic environments than previously described. Interestingly, we also identified a putative novel clade of acoels in the deep benthos that branches as sister group to the rest of Acoela, thus representing the earliest-branching acoel clade. Our data highlight deep-sea environments as an ideal habitat to sample acoels with key phylogenetic positions, which might be useful for reconstructing the early evolution of Bilateria. PMID- 27677820 TI - Placoderms and the evolutionary origin of teeth: a comment on Rucklin & Donoghue (2015). PMID- 27677821 TI - Reply to 'placoderms and the evolutionary origin of teeth': Burrow et al. (2016). PMID- 27677822 TI - Spanish version of Pregnancy Symptoms Inventory: transcultural adaptation and reliability. AB - AIM: To transcultural adapt and analyze the reliability of Spanish version of Pregnancy Symptoms Inventory (PSI) and assess the prevalence of pregnancy symptoms in Spanish pregnant women. MATERIALS AND METHODS: A subsample of 120 healthy pregnant women answered the PSI twice and a sample of 280 report the prevalence and limitation of pregnancy symptoms. The reliability was examined by means of percent agreement and weighted Kappa coefficients. The prevalence of pregnancy symptoms was evaluated by the frequency of answers. RESULTS: Perfect and perfect-acceptable agreement was observed in 82% and 96% of the pregnant women, respectively. Weighted Kappa coefficients ranged from 0.589 to 0.889, indicating a good reliability. The most frequent symptoms perceived by Spanish pregnant women were urinary frequency, poor sleep, increased vaginal discharge and tiredness. CONCLUSION: Spanish Pregnancy Symptoms Inventory is a brief, conceptually equivalent and satisfactory reliable tool that allows an early assessment of the wide range of pregnancy symptoms in the health care practices. PMID- 27677824 TI - Lip Attractiveness: A Cross-Cultural Analysis. AB - Background: Perception of beauty is influenced by the individual's geographic, ethnic, cultural, and demographic background. However, objective measurements remain the foundation for aesthetic evaluations. In the quest for to better define "ideal" lip characteristics, this study assumes interdependence between variables such as country of residence, sex, age, occupation, and aesthetic perception. Objectives: This study will increase surgeons' awareness with respect to different lip size preferences. The provided information might enhance and clarify communication among plastic surgeons and aid to put often quoted "ideal proportions" in context. Methods: An online survey was designed. Modifiable ranges of lip fullness were achieved via digital alteration, enabling participants to interactively change the shape of a single model's lips. The questionnaire was sent to more than 9000 plastic surgeons and laypeople worldwide. Demographic data were collected and analysis of variance was used to elucidate lip shape preferences. Results: A total of 1011 responses (14% response rate) from 35 different countries were gathered. Significant differences regarding lip fullness were identified. Surgeons who practice in Asia or non Caucasian surgeons prefer larger lips, while those in Europe and Caucasians prefer smaller lips. Lastly, laypersons living in Asia prefer the smallest lips. Conclusions: Country of residence, ethnic background, and profession significantly impact individual lip shape preferences. These findings have implications for patients and surgeons, because differences in aesthetics' preferences can lead to dissatisfaction of patients and surgeons alike. In our increasingly global environment, cultural differences and international variability must be considered when defining new aesthetic techniques, treating patients, and reporting outcomes. PMID- 27677825 TI - The Modern Polyurethane-Coated Implant in Breast Augmentation: Long-Term Clinical Experience. AB - BACKGROUND: First-generation polyurethane foam-coated breast implants were associated with a low risk of capsular contracture (CC), but the risk of CC with modern polyurethane-coated silicone implants has not been established. OBJECTIVES: The authors sought to determine the long-term rates of CC after primary breast augmentation with Microthane, a polyurethane-coated silicone gel implant. METHODS: A total of 131 patients (255 breasts) were evaluated in a retrospective study. Data were compiled from postoperative follow-up sessions at 2 weeks; 1, 3, 6, and 12 months; and annually thereafter. Rates of various complications, including CC, were determined. RESULTS: CC developed in 3 of the 255 implanted breasts (1.2%; Baker grade III or IV), and postoperative hematoma occurred in 2 implanted breasts (0.8%). Spontaneous CC that was not associated with other complications was observed in 1 implanted breast (0.4%). All instances of CC occurred before the 31st postoperative month. CONCLUSIONS: For patients who undergo primary breast augmentation with modern polyurethane-coated implants, the long-term risk of CC is low. LEVEL OF EVIDENCE: 3 Therapeutic. PMID- 27677826 TI - In silico screening, molecular docking, and molecular dynamics studies of SNP derived human P5CR mutants. AB - Pyrroline-5-carboxylate reductase (P5CR) encoded by PYCR1 gene is a housekeeping enzyme that catalyzes the reduction of P5C to proline using NAD(P)H as the cofactor. In this study, we used in silico approaches to examine the role of nonsynonymous single-nucleotide polymorphisms in the PYCR1 gene and their putative functions in the pathogenesis of Cutis Laxa. Among the 348 identified SNPs, 15 were predicted to be potentially damaging by both SIFT and PolyPhen tools; of them two SNP-derived mutations, R119G and G206W, have been previously reported to correlate with Cutis Laxa. These two mutations were therefore selected to be mapped to the wild-type (WT) P5CR structure for further structural and functional analyses. The results of comparative computational analyses using I-Mutant and Autodock reveal reductions in both stability and cofactor binding affinity of these two mutants. Comparative molecular dynamics (MD) simulations were performed to evaluate the changes in dynamic properties of P5CR upon mutations. The results reveal that the two mutations enhance the rigidity of P5CR structure, especially that of cofactor binding site, which could result in decreased kinetics of cofactor entrance and egress. Comparison between the structural properties of the WT and mutants during MD simulations shows that the enhanced rigidity of mutants results most likely from the increased number of inter-atomic interactions and the decreased number of dynamic hydrogen bonds. Our study provides novel insight into the deleterious effects of the R119G and G206W mutations on P5CR, and sheds light on the mechanisms by which these mutations mediate Cutis Laxa. PMID- 27677827 TI - A Virtual Reality avatar interaction (VRai) platform to assess residual executive dysfunction in active military personnel with previous mild traumatic brain injury: proof of concept. AB - PURPOSE: This proof of concept study tested the ability of a dual task walking protocol using a recently developed avatar-based virtual reality (VR) platform to detect differences between military personnel post mild traumatic brain injury (mTBI) and healthy controls. METHODS: The VR platform coordinated motion capture, an interaction and rendering system, and a projection system to present first (participant-controlled) and third person avatars within the context of a specific military patrol scene. A divided attention task was also added. A healthy control group was compared to a group with previous mTBI (both groups comprised of six military personnel) and a repeated measures ANOVA tested for differences between conditions and groups based on recognition errors, walking speed and fluidity and obstacle clearance. RESULTS: The VR platform was well tolerated by both groups. Walking fluidity was degraded for the control group within the more complex navigational dual tasking involving avatars, and appeared greatest in the dual tasking with the interacting avatar. This navigational behaviour was not seen in the mTBI group. CONCLUSIONS: The present findings show proof of concept for using avatars, particularly more interactive avatars, to expose differences in executive functioning when applying context-specific protocols (here for the military). Implications for rehabilitation Virtual reality provides a means to control context-specific factors for assessment and intervention. Adding human interaction and agency through avatars increases the ecologic nature of the virtual environment. Avatars in the present application of the Virtual Reality avatar interaction platform appear to provide a better ability to reveal differences between trained, military personal with and without mTBI. PMID- 27677828 TI - Sunitinib for the treatment of thyroid cancer. AB - INTRODUCTION: Sunitinib is an oral oxindol derivative and a potent inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor and a multitargeted tyrosine-kinase inhibitor, which has antitumor and antiangiogenic activity due to the selective inhibition that can stabilize progressive metastatic disease. The aim of this review is to expose whether the drug could be considered as a new promising therapy compared with other tyrosine kinase inhibitors. Areas covered: In seven open-label studies carried out with sunitinb, the drug showed its anti-tumoral activity in advanced differentiated thyroid carcinoma and in medullary thyroid carcinoma. The reported objectives in advanced differentiated thyroid carcinoma, partial response ranges 13% to 55.5%, stable disease ranges 44.4% to 68%, progressive disease ranges 10% to 21% of patients, progression free survival ranges 3 to 13.3% months. In medullary thyroid carcinoma, PR ranges 0% to 55%, SD ranges 44.4% to 87.5%, PD ranges 7% to 18.8% and progression free survivalranges seven to 21 months. Expert opinion: Sunitinib has demonstrated a potent anti-tumoral activity in differentiated thyroid carcinoma and in medullary thyroid carcinoma, but the results of the open label trials single arm are limited. Further investigations with this agent with randomized trials are warranted. PMID- 27677829 TI - Plant phenyl-propanoids-conjugated silver nanoparticles from edible plant Suaeda maritima (L.) dumort. Inhibit proliferation of K562-human myeloid leukemia cells. AB - The present study portrays the isolation of four phenylpropanoids - ferulic acid (FA), sinapic acid (SA), caffeic acid (CA), and chlorogenic acid (CHA) from the water extract of Suaeda maritima (L.) Dumort, a phytochemically less explored Indian medicinal plant. Further, synthesis and characterization of silver and gold nanoparticles using the isolated phenylpropanoids were done. The silver nanoparticles synthesized from S. maritima water extract along with silver nano conjugated forms of the isolated compounds exhibited appreciable anti-leukemic activity against K562 cells (human myeloid leukemia). Especially, the ferulic and CA-conjugated silver nanoparticles showed significant (P < .01) activity against leukemia. PMID- 27677830 TI - Psychiatric evaluation of youths with Disruptive Behavior Disorders and psychopathic traits: A critical review of assessment measures. AB - Disruptive Behavior Disorders (DBDs) are stable and impairing disorders, heterogeneous in presentation, developmental pathways, and treatment needs. Disentangling subtypes according to psychopathological dimensions is helpful for timely diagnoses, precise prognoses and tailored interventions. Psychopathic traits are relevant in subtyping DBDs with severe antisocial and aggressive behaviors. Three psychopathy dimensions have been found: 1) an affective dimension, the callous-unemotional (CU) trait, with lack of empathy and remorse, and with short-lived emotions; 2) an interpersonal dimension, the narcissistic domain, with manipulative abilities, superficial charm, egocentricity and grandiosity; 3) a behavioral dimension, the impulsivity or impulsive irresponsibility, with irresponsibility, proneness to boredom, and novelty seeking. Recently, research suggests that youth with CU traits, similarly to adults with psychopathy, can present a low-anxious "primary" and high-anxious "secondary" variants. Our aim is to critically review the main measures of psychopathic traits, including the three main dimensions (with specific emphasis on CU traits), and the "primary/secondary" distinction, focusing on the assessment in clinical settings. An assessment procedure is proposed, based on previous literature and personal clinical experience. PMID- 27677831 TI - Therapeutic effects of an alpha-casozepine and L-tryptophan supplemented diet on fear and anxiety in the cat. AB - Objectives This study assessed the anxiolytic effectiveness of a test diet (Royal Canin Feline Calm diet) supplemented with L-tryptophan and alpha-casozepine. Methods Subjects were 24 cats that were classified as mildly or markedly fearful based on the presence of a person in their home room. Three different protocols were used to assess anxiety: (1) evaluation of the response to a human in the cat's home room (home room test); (2) analysis of the response to placement in an empty test room (open-field test); and (3) analysis of the response to an unfamiliar human (human interaction test). All three protocols were first run at baseline, and the results were used to assign the animals to control and test diet groups that showed equivalent fear and anxiety. Both groups were retested on the three protocols after 2 weeks (test 1) and again after 4 weeks (test 2). Results The diet groups differed for two behavioral measures in the open-field test: inactivity duration and inactivity frequency. The control group showed statistically significant increases in inactivity duration between baseline and test 1 and baseline and test 2, while the group fed the test diet showed a marginally not significant decrease in inactivity duration between baseline and test 1 and a not significant decrease for test 2. There was also a significant increase in inactivity frequency between baseline and test 1 in the test diet group and marginally not significant decrease in the control group. There were no differences between groups in the approach of the cats toward people for the home room test and the human interaction test. Conclusions and relevance These results suggest that the test diet reduced the anxiety response to placement in an unfamiliar location, but that fear in the presence of an unfamiliar person was not counteracted by the diet. PMID- 27677832 TI - Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+ monocytes. AB - Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+ monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+ enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-alpha, TNFalpha, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16- monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-alpha was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+ monocytes, favoring leukocyte infiltration in the obese omental AT. PMID- 27677833 TI - Parasitic and infectious diseases of the biliary tract in migrants and international travelers. AB - INTRODUCTION: In recent years, global and regional crises have led to extraordinary worldwide migration, accompanied by an increase in long-distance travel from Western countries. Both are linked to a rising incidence of rare parasitic and infectious diseases in first world countries, including in the biliary tract. Areas covered: A selective literature research in PubMed was performed to review the most important parasitic and infectious biliary diseases, which are caused by a wide variety of pathogens and may be latent over long periods, with chronic courses leading to cholangitis, hepatic failure or development of cholangiocarcinoma. Parasites such as Ascaris, Fasciola and Clonorchis/Opisthorchis are particularly important and may trigger biliary diseases or predisposition for bacterial superinfections. Viral or protozoal cholangitis is mainly a problem of impaired immunity. Expert commentary: Currently, these entities are still rare in migrants and long-distance travelers. However, a significant increase in Western countries has to be expected. Incidences are most likely underestimated because of protracted clinical latency. Diagnosis depends on the relevant pathogens, the host's immune status and the extent or distribution of biliary obstruction. Modern tomographic methods, ERCP and specific microbiological/parasitological/virological tests are of crucial diagnostic importance. Antimicrobial/antiparasitic/antiviral therapy along with ERCP and interventional sonography/radiology provide effective treatment options. PMID- 27677834 TI - Frontline Science: Human bone cells as a source of IL-27 under inflammatory conditions: role of TLRs and cytokines. AB - IL-27 regulates immune responses as well as hematopoiesis and bone remodeling, but its cellular sources in the bone remain unknown. In this study, we investigated whether osteoclasts and osteoblasts-the 2 cell types orchestrating bone homeostasis-could be a source of IL-27 and identified stimuli that induce its expression in vitro. We observed that human monocyte-derived osteoclasts expressed a broader range of TLRs than did human primary osteoblasts and that both cell types exhibited a differential induction of IL-27 expression in response to TLR or cytokine stimulation. Whereas several TLR agonists, notably TLR4 and TLR7/8 agonists, induced substantial expression of IL-27 by osteoclasts, stimulation of osteoblasts with agonists of TLR3 and/or TLR4-the 2 TLRs selectively expressed by these cells-resulted in no or low IL-27 expression. In addition, IL-27 increased TLR3 expression in osteoclasts and enhanced poly(I:C) mediated induction of IL-27 in these cells. IFN-gamma, when combined with either IL-1beta plus TNF-alpha, IL-11, or CNTF, induced significant levels of IL-27 in osteoclasts but not in osteoblasts. In the latter cells, the addition of type I IFN, together with proinflammatory cytokines, was necessary to induce substantial levels of IL-27. Immunohistochemical studies of inflamed and remodeling bone tissue, including cases of infectious osteomyelitis and bone metastases, provided evidence that osteoclasts, osteoblasts, and occasionally osteocytes or chondrocytes, could express IL-27 in situ. This autocrine production of IL-27 by TLR- or cytokine-activated bone cells might constitute a negative-feedback mechanism to limit bone erosion and to dampen T cell-mediated immune pathology during bone inflammation. PMID- 27677835 TI - Optical manipulation of single flux quanta. AB - Magnetic field can penetrate into type II superconductors in the form of Abrikosov vortices, which are magnetic flux tubes surrounded by circulating supercurrents often trapped at defects referred to as pinning sites. Although the average properties of the vortex matter in superconductors can be tuned with magnetic fields, temperature or electric currents, handling of individual Abrikosov vortices remains challenging and has been demonstrated only with sophisticated scanning local probe microscopies. Here we introduce a far-field optical method based on local heating of the superconductor with a focused laser beam to realize a fast and precise manipulation of individual vortices, in the same way as with optical tweezers. This simple approach provides the perfect basis for sculpting the magnetic flux profile in superconducting devices like a vortex lens or a vortex cleaner, without resorting to static pinning or ratchet effects. PMID- 27677837 TI - Role of Oxidative Stress in the Genesis of Atherosclerosis and Diabetes Mellitus: A Personal Look Back on 50 Years of Research. AB - We have provided an overview, based on the literature and our data. In accordance with the theory of D. Harman free radical processes cause damages that can accumulate and contribute to aging of the organism. Atherosclerosis and diabetes are developing for a long time so they are manifested predominantly in old age. We found an increase in the level of free radical peroxidation products and decrease in the activity of antioxidant enzymes in the tissues of animals with experimental atherosclerosis. Similar changes were found in the blood of patients with atherosclerosis and aortic autopsy material with atherosclerotic lesions. Thus, it was revealed that oxidative stress occured under atherosclerosis, and the arteriosclerosis to "Free Radical Pathologies" was attributed. Later it was discovered by different authors that oxidized Low Density Lipoproteins (LDL) and malonyldialdehyde- modified LDL accumulated during atherogenesis, causing damages of vascular wall. Under diabetic hyperglycemia glucose co-oxidized during free radical lipoperoxidation. This process promoted the transformation of oxidative stress to carbonyl stress with accumulation of biologically active dicarbonyls, including glyoxal and methylglyoxal. We show that the glyoxal-modified LDL were captured by cultured macrophages with a higher efficiency than the MDA-modified LDL. This could facilitate the more rapid development of lipoidosis in the vessel wall (due to the formation of foam cells) and manifestation of atherosclerosis under diabetes. We found that in patients with diabetes there was a sharp decrease in the activity of antioxidant enzymes as a result of the modification of the active center under development of carbonyl stress. We expressed a hypothesis about a common molecular mechanism of vascular wall damages under atherosclerosis and diabetes. PMID- 27677836 TI - Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the BIOBADADERM Registry. AB - Information regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression. Our study included records of 2,153 patients (7,867.5 person years). The adjusted RR of overall infection was significantly increased in the groups treated with adalimumab with methotrexate (adjusted RR = 2.13, 95% confidence interval [CI] = 1.2-3.7), infliximab (adjusted RR = 1.71, 95% CI = 1.1 2.65), cyclosporine (adjusted RR = 1.58, 95% CI = 1.17-2.15), ustekinumab with methotrexate (adjusted RR = 1.56, 95% CI = 1.08-2.25), and etanercept (adjusted RR = 1.34, 95% CI: 1.02-1.76) compared with methotrexate alone. Cyclosporine had a significant risk of serious infection (adjusted RR = 3.12, 95% CI = 1.1-8.8), followed by adalimumab combined with methotrexate (adjusted RR = 3.28, 95% CI = 0.8-13.5). Adalimumab in combination with methotrexate had the highest risk of infection recurrence (adjusted RR = 4.33, 95% CI = 2.27-8.24). PMID- 27677838 TI - Competitive males have higher quality sperm in a monogamous social bee. AB - BACKGROUND: Reproductive success is determined by the interplay between mating and fertilization success. In social insect species with male-biased sex ratios and queen monogamy, males face particularly strong pre-copulatory sexual selection since they must compete with thousands of other males for a unique mating opportunity. Ejaculate quality is also expected to be under selection, because queens are long-lived and store sperm for life, so males with higher quality ejaculates are expected to provide queens with larger and longer-lived colonies, which in turn may produce more daughter queens (the only direct fitness gains of haplodiploid males). Considering the action of pre and post-copulatory sexual selection on male traits, three scenarios might thus be expected: positive, negative or no association between male mating ability and fertilization success. Here we explored these scenarios in the stingless bee Scaptotrigona aff. depilis, where males gather in large aggregations and queens mate with a single male. Male mating ability was assessed through the capacity of a male to reach an aggregation and persist on it; while sperm viability, sperm number, and sperm morphology were used as proxies for sperm quality. RESULTS: Sperm viability was associated with persistence time in the aggregation, and males that persisted longer presented shorter spermatozoa and higher variation in sperm length than recently arrived males. However, sperm traits of males that reached aggregations did not differ from those of males collected inside their colonies. In addition, males that persisted longer in aggregations were smaller than other males. Male size and sperm viability were not correlated, suggesting that the observed patterns were not due to trade-offs in male resource allocation. CONCLUSIONS: Persistence in male aggregations thus seems to select more competitive males with higher quality sperm. Our work is the first one to reveal an association between male competitive ability and fertilization success in a monogamous social insect. This finding sheds important light on the evolution of male traits in social insects and the general mechanisms of sexual selection. PMID- 27677841 TI - Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells. AB - The epithelial response to the opportunistic pathogen Campylobacter concisus is poorly characterised. Here, we assessed the intestinal epithelial responses to two C. concisus strains with different virulence characteristics in Caco-2 cells using RNAseq, and validated a subset of the response using qPCR arrays. C. concisus strains induced distinct response patterns from intestinal epithelial cells, with the toxigenic strain inducing a significantly more amplified response. A range of cellular functions were significantly regulated in a strain specific manner, including epithelial-to-mesenchymal transition (NOTCH and Hedgehog), cytoskeletal remodeling, tight junctions, inflammatory responses and autophagy. Pattern recognition receptors were regulated, including TLR3 and IFI16, suggesting that nucleic acid sensing was important for epithelial recognition of C. concisus. C. concisus zonula occludens toxin (ZOT) was expressed and purified, and the epithelial response to the toxin was analysed using RNAseq. ZOT upregulated PAR2 expression, as well as processes related to tight junctions and cytoskeletal remodeling. C. concisus ZOT also induced upregulation of TLR3, pro-inflammatory cytokines IL6, IL8 and chemokine CXCL16, as well as the executioner caspase CASP7. Here, we characterise distinct global epithelial responses to C. concisus strains, and the virulence factor ZOT, and provide novel information on mechanisms by which this bacterium may affect the host. PMID- 27677839 TI - The complex evolutionary history of the tympanic middle ear in frogs and toads (Anura). AB - Most anurans possess a tympanic middle ear (TME) that transmits sound waves to the inner ear; however, numerous species lack some or all TME components. To understand the evolution of these structures, we undertook a comprehensive assessment of their occurrence across anurans and performed ancestral character state reconstructions. Our analysis indicates that the TME was completely lost at least 38 independent times in Anura. The inferred evolutionary history of the TME is exceptionally complex in true toads (Bufonidae), where it was lost in the most recent common ancestor, preceding a radiation of >150 earless species. Following that initial loss, independent regains of some or all TME structures were inferred within two minor clades and in a radiation of >400 species. The reappearance of the TME in the latter clade was followed by at least 10 losses of the entire TME. The many losses and gains of the TME in anurans is unparalleled among tetrapods. Our results show that anurans, and especially bufonid toads, are an excellent model to study the behavioural correlates of earlessness, extratympanic sound pathways, and the genetic and developmental mechanisms that underlie the morphogenesis of TME structures. PMID- 27677842 TI - Synthesis, characterization and drug loading property of Monomethoxy Poly(ethylene glycol)-Poly(epsilon-caprolactone)-Poly(D,L-lactide) (MPEG-PCLA) copolymers. AB - Amphiphilic block copolymers have attracted a great deal of attention in drug delivery systems. In this work, a series of monomethoxy-poly (ethylene glycol) poly (epsilon-caprolactone-co-D,L-lactide) (MPEG-PCLA) copolymers with variable composition of poly (epsilon-caprolactone) (PCL) and poly (D,L-lactide) (PDLLA) were prepared via ring-opening copolymerization of epsilon-CL and D,L-LA in the presence of MPEG and stannous octoate. The structure and molecular weight were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The crystallinity, hydrophilicity, thermal stability and hydrolytic degradation behavior were investigated in detail, respectively. The results showed that the prepared amphiphilic MPEG-PCLA copolymers have adjustable properties by altering the composition of PCLA, which make it convenient for clinical applications. Besides, the drug loading properties were also studied. Docetaxel (DTX) could be entrapped in MPEG-PCLA micelles with high loading capacity and encapsulation efficiency. And all lyophilized DTX-loaded MPEG-PCLA micelles except MPEG-PCL micelles were readily re-dissolved in normal saline at 25 degrees C. In addition, DTX-loaded MPEG-PCLA micelles showed a slightly enhanced antitumor activity compared with free DTX. Furthermore, DTX micelles exhibited a slower and sustained release behavior in vitro, and higher DTX concentration and longer retention time in vivo. The results suggested that the MPEG-PCLA copolymer with the adjustable ratio of PCL to PDLLA may be a promising drug delivery carrier for DTX. PMID- 27677844 TI - Patient health questionnaire-9 versus Edinburgh postnatal depression scale in screening for major depressive episodes: a cross-sectional population-based study. AB - BACKGROUND: Major depressive episodes (MDE) are frequent at the population level and are generally associated with severe symptoms that impair performance of activities of daily living of individuals suffering from this condition. The aim of this study was to compare the accuracy of two tests that separately showed suitable properties in screening for MDE: the Patient Health Questionnaire-9 (PHQ 9) and the Edinburgh postnatal depression scale (EPDS). METHODS: In a previous study, the sensitivity and specificity of the PHQ-9 and the EPDS in screening for MDE were compared with a structured diagnostic interview conducted by psychiatrics and psychologists using the Mini International Neuropsychiatric Interview as the gold standard. In a sample of adults living in the community in Pelotas, Brazil, the PHQ-9 and EPDS were applied at the same interview and the gold standard on a median of 17 days later. The interviews were carried out at the participant's home. RESULTS: 447 individuals (191 men and 256 women) were assessed. The PHQ-9 and the EPDS results were concordant in 87.5 % of the respondents, with a moderate agreement beyond what was expected by chance alone (kappa = 0.61). The areas below the ROC curves were not statistically different (82.1 % for PHQ-9 and 83.5 % for EPDS) (p = 0.291), thus indicating that the two tests had similar moderate accuracy. CONCLUSIONS: PHQ-9 and EPDS may be applied with equal confidence in screening for MDE in the community. PMID- 27677843 TI - Carbon assimilation in Eucalyptus urophylla grown under high atmospheric CO2 concentrations: A proteomics perspective. AB - : Photosynthetic organisms may be drastically affected by the future climate projections of a considerable increase in CO2 concentrations. Growth under a high concentration of CO2 could stimulate carbon assimilation-especially in C3-type plants. We used a proteomics approach to test the hypothesis of an increase in the abundance of the enzymes involved in carbon assimilation in Eucalyptus urophylla plants grown under conditions of high atmospheric CO2. Our strategy allowed the profiling of all Calvin-Benson cycle enzymes and associated protein species. Among the 816 isolated proteins, those involved in carbon fixation were found to be the most abundant ones. An increase in the abundance of six key enzymes out of the eleven core enzymes involved in carbon fixation was detected in plants grown at a high CO2 concentration. Proteome changes were corroborated by the detection of a decrease in the stomatal aperture and in the vascular bundle area in Eucalyptus urophylla plantlets grown in an environment of high atmospheric CO2. Our proteomics approach indicates a positive metabolic response regarding carbon fixation in a CO2-enriched atmosphere. The slight but significant increase in the abundance of the Calvin enzymes suggests that stomatal closure did not prevent an increase in the carbon assimilation rates. BIOLOGICAL SIGNIFICANCE: The sample enrichment strategy and data analysis used here enabled the identification of all enzymes and most protein isoforms involved in the Calvin-Benson-Bessham cycle in Eucalyptus urophylla. Upon growth in CO2 enriched chambers, Eucalyptus urophylla plantlets responded by reducing the vascular bundle area and stomatal aperture size and by increasing the abundance of six of the eleven core enzymes involved in carbon fixation. Our proteome approach provides an estimate on how a commercially important C3-type plant would respond to an increase in CO2 concentrations. Additionally, confirmation at the protein level of the predicted genes involved in carbon assimilation may be used in plant transformation strategies aiming to increase plant adaptability to climate changes or to increase plant productivity. PMID- 27677845 TI - Resveratrol suppresses NTHi-induced inflammation via up-regulation of the negative regulator MyD88 short. AB - Upper respiratory tract inflammatory diseases such as asthma and chronic obstructive pulmonary diseases (COPD) affect more than one-half billion people globally and are characterized by chronic inflammation that is often exacerbated by respiratory pathogens such as nontypeable Haemophilus influenzae (NTHi). The increasing numbers of antibiotic-resistant bacterial strains and the limited success of currently available pharmaceuticals used to manage the symptoms of these diseases present an urgent need for the development of novel anti inflammatory therapeutic agents. Resveratrol has long been thought as an interesting therapeutic agent for various diseases including inflammatory diseases. However, the molecular mechanisms underlying its anti-inflammatory properties remain largely unknown. Here we show for the first time that resveratrol decreases expression of pro-inflammatory mediators in airway epithelial cells and in the lung of mice by enhancing NTHi-induced MyD88 short, a negative regulator of inflammation, via inhibition of ERK1/2 activation. Furthermore, resveratrol inhibits NTHi-induced ERK1/2 phosphorylation by increasing MKP-1 expression via a cAMP-PKA-dependent signaling pathway. Finally, we show that resveratrol has anti-inflammatory effects post NTHi infection, thereby demonstrating its therapeutic potential. Together these data reveal a novel mechanism by which resveratrol alleviates NTHi-induced inflammation in airway disease by up-regulating the negative regulator of inflammation MyD88s. PMID- 27677846 TI - Evaluation of Ajuga bracteosa for antioxidant, anti-inflammatory, analgesic, antidepressant and anticoagulant activities. AB - BACKGROUND: Ajuga bracteosa has been extensively used traditionally for the treatment of a variety of diseases. The aim of the study was to scientifically validate the wide-scale exploitation of A. bracteosa in folk medicine various in vitro and in vivo assays. Moreover, these activities were related to the intrinsic biologically active phytoecdysteroids of A. bracteosa. METHODS: Aerial and root parts of A. bracteosa were first extracted separately with chloroform (AbCA and AbCR) and the residue was again extracted with methanol (AbMA and AbMR). Total flavonoid and phenolic contents were assayed as quercetin (QE) and gallic acid equivalents (GAE), respectively. These extracts were analyzed for in vitro antioxidant assessment including DPPH and H2O2 (% inhibition of free radicals), and reducing power and phosphomolybdenum methods (ascorbic acid equivalents AAE mg/g DW). Further, these extracts were assayed in vivo in separate groups of Sprague-Dawley rats for carrageenan induced rat paw edema inhibition, hotplate antinociception, forced swim antidepression and anticoagulation. Dose of each crude extract and standard drug given to rats was 200 mg/Kg- and 10 mg/10 mL/Kg body weight respectively. Plant extracts and standard drugs were administered orally, 60 min prior to the conduction of assays. Moreover, biologically active phytoecdysteroids were screened in A. bracteosa with the help of RP-HPLC. RESULTS: AbMA represented highest values of flavonoids (QE 1.98 % DW) and phenolic contents (GAE 5.94 % DW), significantly scavenged DPPH radicles (IC50 36.9) and reduced ferric ions with 718.4 mg ascorbic acid equivalent/g (AAE). Highest total antioxidant capacity was expressed by AbMR (927 mg AAE) with an IC50 value 19.1 MUg/mL. The extracts which were found potent anti-oxidants, were also good at in vivo activities. AbMA significantly reduced edema in all the three hours of treatment (67.9, 70.3 and 74.3 %). AbMA also showed maximum nociceptor suppression in analgesic assay by delaying the time to start licking of paws in rats (57.7 +/- 4.9 s). In addition, maximum anti-coagulation was also exhibited by AbMA (89.3 s), while all extracts were found strong antidepressants (<=15.66 s immobility time). Screening of biologically active phytoecdysteroids revealed the presence of 20-hydroxyecdysone (20-HE), makisterone (MKA), cyasterone (CYP) and ajujalactone (AJL). Total phytoecdysteroid content found in A. bracteosa was 1232.5 MUg/g DW and 20-HE was most abundant (1232.5 MUg/g DW) as compared to other phytoecdysteroids. CONCLUSION: Based on the tested in vitro and in vivo activities, AbMA was found to be a promising bioactive extract. These activities can be attributed to the intrinsic polyphenols and phytoecdysteroids contents of A. bracteosa. PMID- 27677847 TI - A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. AB - Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like in their structure, cellular diversity and function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled human fetal lung tissue in vitro (Dye et al., 2015). Here we show that HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. By further comparing in vitro and in vivo grown HLOs with fetal and adult human lung tissue, we found that in vivo transplanted HLOs had improved cellular differentiation of secretory lineages that is reflective of differences between fetal and adult tissue, resulting in airway-like structures that were remarkably similar to the native adult human lung. PMID- 27677848 TI - Synchronized excitability in a network enables generation of internal neuronal sequences. AB - Hippocampal place field sequences are supported by sensory cues and network internal mechanisms. In contrast, sharp-wave (SPW) sequences, theta sequences, and episode field sequences are internally generated. The relationship of these sequences to memory is unclear. SPW sequences have been shown to support learning and have been assumed to also support episodic memory. Conversely, we demonstrate these SPW sequences were present in trained rats even after episodic memory was impaired and after other internal sequences - episode field and theta sequences - were eliminated. SPW sequences did not support memory despite continuing to 'replay' all task-related sequences - place- field and episode field sequences. Sequence replay occurred selectively during synchronous increases of population excitability -- SPWs. Similarly, theta sequences depended on the presence of repeated synchronized waves of excitability - theta oscillations. Thus, we suggest that either intermittent or rhythmic synchronized changes of excitability trigger sequential firing of neurons, which in turn supports learning and/or memory. PMID- 27677850 TI - Taxonomic and functional diversity increase the aesthetic value of coralligenous reefs. AB - The aesthetic value of landscapes contributes to human well-being. However, studies which have investigated the link between biodiversity and ecosystem services have not taken aesthetic value into account. In this study we evaluated how the aesthetics of coralligenous reefs, a key marine ecosystem in the Mediterranean, is perceived by the general public and how aesthetic preferences are related to biodiversity facets (taxonomic, phylogenetic and functional diversities). We performed both biodiversity measures and online-surveys of aesthetic perception on photographic quadrats sampled along the French Mediterranean coast. Our results show that species richness and functional richness have a significant positive effect on aesthetic value. Most of the ecological literature, exploring the relationship between biodiversity and ecosystem functioning and service has focused so far on 'economical' aspects of biodiversity (provision or regulation). Our results illustrate that cultural facets, such as 'beauty', should also be central in our motivations to preserve ecological diversity. PMID- 27677849 TI - Unconventional secretory processing diversifies neuronal ion channel properties. AB - N-glycosylation - the sequential addition of complex sugars to adhesion proteins, neurotransmitter receptors, ion channels and secreted trophic factors as they progress through the endoplasmic reticulum and the Golgi apparatus - is one of the most frequent protein modifications. In mammals, most organ-specific N glycosylation events occur in the brain. Yet, little is known about the nature, function and regulation of N-glycosylation in neurons. Using imaging, quantitative immunoblotting and mass spectrometry, we show that hundreds of neuronal surface membrane proteins are core-glycosylated, resulting in the neuronal membrane displaying surprisingly high levels of glycosylation profiles that are classically associated with immature intracellular proteins. We report that while N-glycosylation is generally required for dendritic development and glutamate receptor surface expression, core-glycosylated proteins are sufficient to sustain these processes, and are thus functional. This atypical glycosylation of surface neuronal proteins can be attributed to a bypass or a hypo-function of the Golgi apparatus. Core-glycosylation is regulated by synaptic activity, modulates synaptic signaling and accelerates the turnover of GluA2-containing glutamate receptors, revealing a novel mechanism that controls the composition and sensing properties of the neuronal membrane. PMID- 27677852 TI - Dimethylarginine Dimethylaminohydrolase 2 (DDAH 2) Gene Polymorphism, Asymmetric Dimethylarginine (ADMA) Concentrations, and Risk of Coronary Artery Disease: A Case-Control Study. AB - Asymmetric dimethylarginine (ADMA) has been shown to be an independent predictor of cardiovascular diseases. Dimethylarginine dimethylaminohydrolase 2 (DDAH 2) promotes the metabolism of ADMA and plays a key role in the regulation of acute inflammatory response. With the present study, we investigated the relationship between DDAH 2 polymorphisms and risk of coronary artery disease (CAD) and its association to plasma ADMA concentrations. We used the haplotype-tagging SNP approach to identify tag SNPs in DDAH 2. The SNPs were genotyped by PCR and sequenced in 385 CAD patients and 353 healthy controls. Plasma concentrations of ADMA were determined using enzyme-linked immunosorbent assay (ELISA). A promoter polymorphism -449C/G (rs805305) in DDAH 2 was identified. Compared with the ADMA concentrations in CC genotype (0.328 +/- 0.077 MUmol/l), ADMA concentrations in CG + GG genotype were significantly increased (0.517 +/- 0.090 MUmol/l, P < 0.001). No significant associations between the -449C/G and risk of CAD were detected in the genetic models. The results of this study suggest that Genetic 499C/G polymorphism in DDAH 2 gene may affect the plasma ADMA concentrations in patients with CAD. However, it does not indicate a novel genetic risk marker for CAD. PMID- 27677853 TI - Messages promoting genetic modification of crops in the context of climate change: Evidence for psychological reactance. AB - Genetic modification (GM) of crops and climate change are arguably two of today's most challenging science communication issues. Increasingly, these two issues are connected in messages proposing GM as a viable option for ensuring global food security threatened by climate change. This study examines the effects of messages promoting the benefits of GM in the context of climate change. Further, it examines whether explicit reference to "climate change," or "global warming" in a GM message results in different effects than each other, or an implicit climate reference. An online sample of U.S. participants (N = 1050) were randomly assigned to one of four conditions: "climate change" cue, "global warming" cue, implicit cue, or control (no message). Generally speaking, framing GM crops as a way to help ensure global food security proved to be an effective messaging strategy in increasing positive attitudes toward GM. In addition, the implicit cue condition led to liberals having more positive attitudes and behavioral intentions toward GM than the "climate change" cue condition, an effect mediated by message evaluations. PMID- 27677851 TI - PARP inhibition in leukocytes diminishes inflammation via effects on integrins/cytoskeleton and protects the blood-brain barrier. AB - BACKGROUND: Blood-brain barrier (BBB) dysfunction/disruption followed by leukocyte infiltration into the brain causes neuroinflammation and contributes to morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. The identification of pathways that decreases the inflammatory potential of leukocytes would prevent such injury. Poly(ADP-ribose) polymerase 1 (PARP) controls various genes via its interaction with myriad transcription factors. Selective PARP inhibitors have appeared lately as potent anti-inflammatory tools. Their effects are outside the recognized PARP functions in DNA repair and transcriptional regulation. In this study, we explored the idea that selective inhibition of PARP in leukocytes would diminish their engagement of the brain endothelium. METHODS: Cerebral vascular changes and leukocyte-endothelium interactions were surveyed by intravital videomicroscopy utilizing a novel in vivo model of localized aseptic meningitis when TNFalpha was introduced intracerebrally in wild-type (PARP+/+) and PARP-deficient (PARP-/-) mice. The effects of selective PARP inhibition on primary human monocytes ability to adhere to or migrate across the BBB were also tested in vitro, employing primary human brain microvascular endothelial cells (BMVEC) as an in vitro model of the BBB. RESULTS: PARP suppression in monocytes diminished their adhesion to and migration across BBB in vitro models and prevented barrier injury. In monocytes, PARP inactivation decreased conformational activation of integrins that plays a key role in their tissue infiltration. Such changes were mediated by suppression of activation of small Rho GTPases and cytoskeletal rearrangements in monocytes. In vitro observations were confirmed in vivo showing diminished leukocyte endothelial interaction after selective PARP suppression in leukocytes accompanied by BBB protection. PARP knockout animals demonstrated a substantial diminution of inflammatory responses in brain microvasculature and a decrease in BBB permeability. CONCLUSIONS: These results suggest PARP inhibition in leukocytes as a novel approach to BBB protection in the setting of endothelial dysfunction caused by inflammation-induced leukocyte engagement. PMID- 27677854 TI - Associations among measures of energy balance related behaviors and psychosocial determinants in urban upper elementary school children. AB - BACKGROUND: Childhood obesity prevention is a pressing issue. Understanding the relationships among eating and physical activity behaviors and potential psychosocial determinants of behavior will help us design more effective interventions. This study aimed to examine such relationships in a large sample of urban elementary school children. METHODS: Fifth grade students in 20 recruited New York City public schools completed a validated questionnaire on six "do more" (fruits and vegetables and physical activity) and "do less" (sweetened beverages, processed packaged snacks, fast food and sedentary behavior) energy balance related behaviors (EBRBs) and psychosocial determinants of behavior from social cognitive and self-determination theories. Correlations among behaviors and hierarchical linear model analyses of the relationship between psychosocial determinants and behaviors were conducted for those with complete data (n = 952). RESULTS: The "do more" and the "do less" behaviors were significantly correlated within categories (p < 0.01). "Do more" food-related behaviors were correlated with physical activity but so were sports drinks, while the "do less" food related behaviors tended to be correlated to sedentary behavior (p < 0.01). "Do more" behaviors were associated with self-efficacy and habit strength, and "do less" behaviors with outcome expectations, self-efficacy, habit strength, and behavioral intention. CONCLUSIONS: Interventions can address the healthy and less healthy clusters of behaviors together, focusing on strategies to enhance their self-efficacy and habit strength for the "do more" behaviors and outcome expectations to motivate intention to choose fewer "do less" behaviors, along with enhancing self-efficacy and habit. Research can examine these determinants as potential mediators of change in intervention. PMID- 27677855 TI - Independent multimerization of Latent TGFbeta Binding Protein-1 stabilized by cross-linking and enhanced by heparan sulfate. AB - TGFbeta plays key roles in fibrosis and cancer progression, and latency is conferred by covalent linkage to latent TGFbeta binding proteins (LTBPs). LTBP1 is essential for TGFbeta folding, secretion, matrix localization and activation but little is known about its structure due to its inherent size and flexibility. Here we show that LTBP1 adopts an extended conformation with stable matrix binding N-terminus, extended central array of 11 calcium-binding EGF domains and flexible TGFbeta-binding C-terminus. Moreover we demonstrate that LTBP1 forms short filament-like structures independent of other matrix components. The termini bind to each other to facilitate linear extension of the filament, while the N-terminal region can serve as a branch-point. Multimerization is enhanced in the presence of heparin and stabilized by the matrix cross-linking enzyme transglutaminase-2. These assemblies will extend the span of LTBP1 to potentially allow simultaneous N-terminal matrix and C-terminal fibrillin interactions providing tethering for TGFbeta activation by mechanical force. PMID- 27677856 TI - Survey of Emergency Physician Approaches to Management of Asymptomatic Hypertension. AB - Uncontrolled hypertension (HTN) is commonly encountered in emergency medicine practice, but the optimal approach to management has not been delineated. The objective of this study was to define emergency physician (EP) approaches to management of asymptomatic HTN in various clinical scenarios and assess adherence to the American College of Emergency Physician clinical policies, utilizing an online survey of EPs. A total of 1200 surveys were distributed by e-mail with completion by 199 participants. The variables associated with a decision to prescribe oral antihypertensive medications were a history of HTN and referral from primary care. Acute blood pressure (BP) reduction using intravenous antihypertensive medications was also more likely with the latter and BP >180/120 mm Hg. Logistic regression revealed association of EP female sex, fewer years in practice, and a high-volume practice setting with guideline-concordant therapy. Wide variability exists in EP approaches to patients with asymptomatic HTN. Treatment decisions were impacted by patient history of chronic HTN, referral from primary care providers, and magnitude of BP elevation. PMID- 27677858 TI - RNA decay: Dhh1p condemns mRNAs with non-optimal codons to decay. PMID- 27677857 TI - Organelle dynamics: Sizing mitochondria with phospholipids. PMID- 27677859 TI - Mechanisms and in vivo functions of contact inhibition of locomotion. AB - Contact inhibition of locomotion (CIL) is a process whereby a cell ceases motility or changes its trajectory upon collision with another cell. CIL was initially characterized more than half a century ago and became a widely studied model system to understand how cells migrate and dynamically interact. Although CIL fell from interest for several decades, the scientific community has recently rediscovered this process. We are now beginning to understand the precise steps of this complex behaviour and to elucidate its regulatory components, including receptors, polarity proteins and cytoskeletal elements. Furthermore, this process is no longer just in vitro phenomenology; we now know from several different in vivo models that CIL is essential for embryogenesis and in governing behaviours such as cell dispersion, boundary formation and collective cell migration. In addition, changes in CIL responses have been associated with other physiological processes, such as cancer cell dissemination during metastasis. PMID- 27677862 TI - Sexual selection expedites the evolution of pesticide resistance. AB - The evolution of insecticide resistance by crop pests and disease vectors causes serious problems for agriculture and health. Sexual selection can accelerate or hinder adaptation to abiotic challenges in a variety of ways, but the effect of sexual selection on resistance evolution is little studied. Here, we examine this question using experimental evolution in the pest insect Tribolium castaneum. The experimental removal of sexual selection slowed the evolution of resistance in populations treated with pyrethroid pesticide, and also reduced the rate at which resistance was lost from pesticide-free populations. These results suggest that selection arising from variance in mating and fertilization success can augment natural selection on pesticide resistance, meaning that sexual selection should be considered when designing strategies to limit the evolution of pesticide resistance. PMID- 27677861 TI - Can diaphragmatic ultrasonography performed during the T-tube trial predict weaning failure? The role of diaphragmatic rapid shallow breathing index. AB - BACKGROUND: The rapid shallow breathing index (RSBI), which is the ratio between respiratory rate (RR) and tidal volume (VT), is one of the most widely used indices to predict weaning outcome. Whereas the diaphragm plays a fundamental role in generating VT, in the case of diaphragmatic dysfunction the inspiratory accessory muscles may contribute. If this occurs during a weaning trial, delayed weaning failure is likely since the accessory muscles are more fatigable than the diaphragm. Hence, we hypothesised that the traditional RSBI could be implemented by substituting VT with the ultrasonographic evaluation of diaphragmatic displacement (DD). We named the new index the diaphragmatic-RSBI (D-RSBI). The aim of this study was to compare the ability of the traditional RSBI and D-RSBI to predict weaning failure in ready-to-wean patients. METHODS: We performed a prospective observational study. During a T-tube spontaneous breathing trial (SBT) we simultaneously evaluated right hemidiaphragm displacement (i.e., DD) by using M-mode ultrasonography as well as the RSBI. Outcome of the weaning attempt, length of mechanical ventilation, length of intensive care unit and hospital stay, and hospital mortality were recorded. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic accuracy of D-RSBI and RSBI. RESULTS: We enrolled 51 patients requiring mechanical ventilation for more than 48 h who were ready to perform a SBT. Most of the patients, 34 (66 %), were successfully weaned from mechanical ventilation. When considering the 17 patients that failed the weaning attempt, 11 (64 %) had to be reconnected to the ventilator during the SBT, three (18 %) had to be re-intubated within 48 h of extubation, and three (18 %) required non-invasive ventilation support within 48 h of extubation. The areas under the ROC curves for D-RSBI and RSBI were 0.89 and 0.72, respectively (P = 0.006). CONCLUSIONS: D-RSBI (RR/DD) was more accurate than traditional RSBI (RR/VT) in predicting the weaning outcome. TRIAL REGISTRATION: Our clinical trial was retrospectively registered with ClinicalTrials.gov (identifier: NCT02696018 ). ClinicalTrials.gov processed our record on 25 February 2016. PMID- 27677860 TI - Alternative polyadenylation of mRNA precursors. AB - Alternative polyadenylation (APA) is an RNA-processing mechanism that generates distinct 3' termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. APA exhibits tissue specificity and is important for cell proliferation and differentiation. In this Review, we discuss the roles of APA in diverse cellular processes, including mRNA metabolism, protein diversification and protein localization, and more generally in gene regulation. We also discuss the molecular mechanisms underlying APA, such as variation in the concentration of core processing factors and RNA-binding proteins, as well as transcription based regulation. PMID- 27677863 TI - Metabolism of 3-pentanone under inflammatory conditions. AB - Breath analysis of rats using multi-capillary column ion-mobility spectrometry (MCC-IMS) revealed alterations in acetone and other ketones, including 3 pentanone, during inflammation. The alterations seem likely to result from oxidative branched-chain keto acid (BCKA) catabolism. We therefore tested the hypothesis that 3-pentanone arises during inflammation from increased BCKA oxidation in the liver with consequent accumulation of propionyl-CoA and its condensation products. Male Sprague-Dawley rats were anaesthetised and ventilated for 24 h or until death. Exhaled breath was analysed by MCC-IMS while rats were injected with low and high doses of lipopolysaccharide (LPS), tumour necrosis factor alpha (TNFalpha), or vehicle. The exhaled 3-pentanone peak was identified by pure substance measurements. Blood was collected 12 h after treatment for the determination of cytokine concentrations; transcription enzymes for BCKA catabolism and the activity of the BCKA dehydrogenase were analysed in liver tissue by quantitative real-time PCR and western blotting. Exhaled 3-pentanone decreased in all groups, but minimum concentrations with high-dose LPS (0.24 +/- 0.31 volts; mean +/- SD), low-dose TNFalpha (0.17 +/- 0.10 volts) and high dose TNFalpha (0.13 +/- 0.04 volts) were lower than in vehicle animals (0.27 +/- 0.12 volts). At 60% and 85% survival times (svt) concentrations of exhaled 3 pentanone increased significantly in all animals treated with low-dose LPS, (svt60% 0.38 +/- 0.18 volts, svt85% 0.62 +/- 0.15 volts) and high-dose LPS (0.26 +/- 0.28 volts, 0.40 +/- 0.22 volts), as well as low-dose TNFalpha, (0.20 +/- 0.09 volts, 0.39 +/- 0.17 volts) and high-dose TNFalpha (0.18 +/- 0.06 volts, 0.34 +/- 0.08 volts), but not in vehicle rats (0.27 +/- 0.12 volts, 0.30 +/- 0.09 volts). BCKA catabolism was seen in the liver, with increased expression and activity of the branched-chain alpha-keto acid dehydrogenase (BCKD), lower expression of the propionyl-CoA carboxylase (PCC) subunits, and altered expression levels of BCKD regulating enzymes. Exhaled 3 pentanone may arise from altered BCKA catabolism. Our results suggest that excessive propionyl-CoA is possibly generated from BCKAs via increased activity of BCKD, but may undergo unusual condensation reactions rather than being physiologically processed to methylmalonyl-CoA by PCC. The pattern of 3-pentanone during early and prolonged inflammation suggests that reuse of BCKAs for the synthesis of new proteins might be initially favoured. As inflammatory conditions persist, substrates for cellular energy supply are required which activate irreversible degradation of excessive BCKA to propionyl-CoA yielding increased levels of exhaled 3-pentanone. PMID- 27677864 TI - Reflectance Hyperspectral Imaging for Investigation of Works of Art: Old Master Paintings and Illuminated Manuscripts. AB - Diffuse reflectance hyperspectral imaging, or reflectance imaging spectroscopy, is a sophisticated technique that enables the capture of hundreds of images in contiguous narrow spectral bands (bandwidth < 10 nm), typically in the visible (Vis, 400-750 nm) and the near-infrared (NIR, 750-2500 nm) regions. This sequence of images provides a data set that is called an image-cube or file-cube. Two dimensions of the image-cube are the spatial dimensions of the scene, and the third dimension is the wavelength. In this way, each spatial pixel in the image has an associated reflectance spectrum. This "big data" image-cube allows for the mining of artists' materials and mapping their distribution across the surface of a work of art. Reflectance hyperspectral imaging, introduced in the 1980s by Goetz and co-workers, led to a revolution in the field of remote sensing of the earth and near planets ( Goetz, F. H.; Vane, G.; Solomon, B. N.; Rock, N. Imaging Spectrometry for Earth Remote Sensing . Science , 1985 , 228 , 1147 - 1152 ). In the subsequent decades, thanks to rapid advances in solid-state sensor technology, reflectance hyperspectral imaging, once only available to large government laboratories, was extended to new fields of application, such as monitoring agri-foods, pharmaceutical products, the environment, and cultural heritage. In the 2000s, the potential of this noninvasive technology for the study of artworks became evident and, consequently, the methodology is becoming more widely used in the art conservation science field. Typically hyperspectral reflectance image-cubes contain millions of spectra. Many of these spectra are similar, making the reduction of the data set size an important first step. Thus, image-processing tools based on multivariate techniques, such as principal component analysis (PCA), automated classification methods, or expert knowledge systems, that search for known spectral features are often applied. These algorithms seek to reduce the large number of high-quality spectra to a common subset, which allow identifying and mapping artists' materials and alteration products. Hence, reflectance hyperspectral imaging is finding its place as the starting point to find sites on polychrome surfaces for spot analytical techniques, such as X-ray fluorescence, Raman spectroscopy, and Fourier transform infrared spectroscopy. Reflectance hyperspectral imaging can also provide image products that are a mainstay in the art conservation field, such as color accurate images, broadband near-infrared images, and false-color products. This Account reports on the research activity carried out by two research groups, one at the "Nello Carrara" Institute of Applied Physics of the Italian National Research Council (IFAC-CNR) in Florence and the other at the National Gallery of Art (NGA) in Washington, D.C. Both groups have conducted parallel research, with frequent interchanges, to develop multispectral and hyperspectral imaging systems to study works of art. In the past decade, they have designed and experimented with some of the earliest spectral imaging prototypes for museum applications. In this Account, a brief presentation of the hyperspectral sensor systems is given with case studies showing how reflectance hyperspectral imaging is answering key questions in cultural heritage. PMID- 27677865 TI - The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1beta), and complement. AB - Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1beta), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1beta and MIP-1beta/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1alpha and IL-1beta; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy. PMID- 27677867 TI - Erratum to: Esophageal stent fixation with endoscopic suturing device improves clinical outcomes and reduces complications in patients with locally advanced esophageal cancer prior to neoadjuvant therapy: a large multicenter experience. PMID- 27677866 TI - Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system. AB - The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs. PMID- 27677868 TI - Less pain after transvaginal cholecystectomy: single-center pooled analysis. AB - BACKGROUND: We previously reported outcome after transvaginal cholecystectomy (TVC) from two cohort studies and a randomized controlled trial. We now present a pooled analysis of postoperative pain scores. DESIGN: Single-center data of postoperative pain after TVC from a level II hospital between October 2007 and June 2012. METHODS: Female patients, above 18 years with symptomatic cholecystolithiasis, received either TVC or conventional laparoscopic cholecystectomy (CLC). Follow up 4 days. The primary outcome of the study was pain after surgery. Pain was measured via a visual rating scale. Descriptive statistics include age, body mass index (BMI), ASA grade, surgical times, number of trocars, complications and hospital stay as well as pain medication. Pain data were assessed against histologic findings. RESULTS: The combined register included 316 patients. Of these, 7 patients were excluded from analysis due to conversion to open surgery, complications and denial of follow-up. There were 141 patients in the TVC and 168 in the CLC group. There was no difference in age, ASA grade, surgical times, complications or hospital stay. BMI was significantly different with an average BMI of 27.1 in the TVC and 28.7 in the CLC group (p = 0.027). The numbers of trocars were significantly different as expected. There was no difference in postoperative pain medication. Pain scores were significantly different on day two to four. Multivariate testing revealed no dependence between postoperative pain and histologic findings. CONCLUSION: On smaller patient numbers, we were previously unable to demonstrate a consistently, significant difference for postoperative pain in our cohort and randomized studies. The pooled analysis suggests that there is an advantage with less postoperative pain after transvaginal compared to standard laparoscopic cholecystectomy. PMID- 27677869 TI - Duration of Nil Per Os is causal in hospital length of stay following laparoscopic bariatric surgery. AB - INTRODUCTION: A recent bariatric surgical study demonstrated an inverse relationship of intraoperative hydration with the incidence of extended hospital length of stay (ehLOS: >1 postoperative hospital day). In that study, a post hoc analysis of the preoperative duration of Nil Per Os (NPO) past midnight revealed a significant dose-response association on the incidence of ehLOS, with the lowest incidence (10-12 %) predicted within the 2-5-h NPO interval. As NPO is associated with a state of compensatory dehydration, the objectives of this study were to prospectively examine the role of decreasing preoperative NPO intervals on the incidence of ehLOS in a similar bariatric surgical population and to establish causality of this association. METHODS: Following IRB approval, 168 bariatric surgeries were analyzed following institution of a revised oral water ad libitum policy until 2 h prior to surgery on the incidence of ehLOS. The role of duration of NPO on the incidence of ehLOS was assessed by logistic fit graphs and misclassification rates on the two groups. A statistical process control chart monitored the efficacy of the revised NPO guidelines. RESULTS: There were statistically significant, but not clinical, differences in the incidences of histories of anemia, gastroesophageal reflux disease, previous percutaneous cardiac intervention/percutaneous transluminal coronary artery angioplasty, or preoperative albumin levels between the two groups. There were no perioperative pulmonary aspirations of gastric contents in either group. Following reduction of the oral hydration interval to >=2 h, a 13-15 % incidence of ehLOS was observed within the 2-5-h NPO interval with similar misclassification rates observed between the two groups. CONCLUSIONS: Allowing bariatric patients access to ad libitum water for up to 2 h prior to surgery decreased the incidence of ehLOS. Comparison of the dose-response curves within the 2-5-h NPO intervals before and after introduction of the revised NPO guidelines was similar and confirms causality. PMID- 27677870 TI - Rural Bypass of Critical Access Hospitals in Iowa: Do Visiting Surgical Specialists Make a Difference? AB - PURPOSE: Rural bypass for elective surgical procedures is a challenge for critical access hospitals, yet there are opportunities for rural hospitals to improve local retention of surgical candidates through alternative approaches to developing surgery lines of business. In this study we examine the effect of visiting surgical specialists on the odds of rural bypass. METHODS: Discharge data from the 2011 State Inpatient Databases and State Ambulatory Surgery Databases for Iowa were linked to outreach data from the Office of Statewide Clinical Education Programs and Iowa Physician Information System to model the effect of surgeon specialist supply on rural patients' decision to bypass rural critical access hospitals. FINDINGS: Patients in rural communities with a local general surgeon were more likely to be retained in a community than to bypass. Those in communities with visiting general surgeons were more likely to bypass, as were those in communities with visiting urologists and obstetricians. Patients in communities with visiting ophthalmologists and orthopedic surgeons were at higher odds of being retained for their elective surgeries. CONCLUSION: In addition to known patient and local hospital factors that have an influence on bypass behavior among rural patients seeking elective surgery, availability of surgeon specialists also plays an important role in whether patients bypass or not. Visiting ophthalmologists and orthopedic surgeons were associated with less bypass, as was having local general surgeons. Visiting general surgeons, urologists, and obstetricians were associated with greater odds of bypass. PMID- 27677871 TI - Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice. AB - Memory impairment is a common symptom in patients with neurodegenerative disorders, and its suppression could be beneficial to improve the quality of life of those patients. Z-guggulsterone, a compound extracted from the resin of plant Commiphora whighitii, exhibits numerous pharmacological effects in clinical practice, such as treatment of inflammation, arthritis, obesity and lipid metabolism disorders. However, the role and possible mechanism of Z-guggulsterone on brain-associated memory impairments are largely unknown. This issue was addressed in the present study in a memory impairment model induced by scopolamine, a muscarinic acetylcholine receptor antagonist, using the passive avoidance, Y-maze and Morris water maze tests. Results showed that scopolamine significantly decreased the step-through latency and spontaneous alternation of C57BL/6J mice in passive avoidance and Y-maze test, whereas increased the mean escape latency and decreased the swimming time in target quadrant in Morris water maze test. Pretreatment of mice with Z-guggulsterone at doses of 30 and 60 mg/kg effectively reversed the scopolamine-induced memory impairments. Mechanistic studies revealed that Z-guggulsterone pretreatment reversed the scopolamine induced increase in acetylcholinesterase (AchE) activity, as well as decreases in brain-derived neurotrophic factor (BDNF) protein expression and cAMP response element-binding protein (CREB), extracellular regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) phosphorylation levels in the hippocampus and cortex. Inhibition of the BDNF signal, however, blocked the memory-enhancing effect of Z guggulsterone. Therefore, these findings demonstrate that Z-guggulsterone attenuates the scopolamine-induced memory impairments mainly through activation of the CREB-BDNF signaling pathway, thereby exhibiting memory-improving effects. PMID- 27677872 TI - Successful coronary surgical stenting: a new hybrid approach. AB - Our goal is to introduce a new hybrid coronary revascularization concept-coronary surgical stenting. The procedure was performed on a 78-year old woman with severe, long and calcified involvement of the proximal left anterior descending artery, chronic total occlusion of the mid-left anterior descending artery and severe disease in the distal left anterior descending artery. An off-pump minimally invasive procedure was performed through the fifth intercostal space, including concurrent surgical placement of a drug-eluting stent in the distal left anterior descending artery, through the left anterior descending artery graft incision, associated with the left internal mammary artery to the mid-left anterior descending artery graft. This procedure resulted in successful revascularization of the left anterior descending artery in a patient with complex coronary disease. PMID- 27677873 TI - Giant mycotic pseudoaneurysm of the aorta protruding over the sternal notch in a child. AB - Aortic mycotic pseudoaneurysms are rare pathologies in children, which are mostly caused by an infection or trauma. Surgical and perioperative antibiotic therapies are mandatory in the treatment. Surgical timing and operational strategy are also critical factors. Herein, we report the successful repair of a giant mycotic pseudoaneurysm of the ascending aorta following a previous cardiac surgery in a 7 year old girl. PMID- 27677874 TI - Cavo-atrial bypass with a polytetrafluoroethylene graft for the treatment of a complete, traumatic transection of the suprahepatic inferior vena cava. AB - In the event of injury to the vena cava, the surgeon's goal is to control the bleeding and then repair the vascular damage. Given the wide range of lesions observed, the repair step has not been standardized. There are a few case reports of simple venoplasty or cavocaval bypass with a polytetrafluoroethylene graft. The present report introduces another treatment option for total avulsion of the suprahepatic inferior vena cava when a lack of remnant venous tissue below the heart prevents direct repair: cavo-atrial bypass with a polytetrafluoroethylene graft. PMID- 27677875 TI - Surgical approach for a symptomatic aortic arch thrombus. AB - Aortic mural thrombus in the normal aorta is an uncommon cause of systemic embolisms. We report the case of a 75-year old male who presented multiple embolic events secondary to a mobile thrombus in the aortic arch. The patient underwent urgent surgery and had an uneventful recovery. He was discharged 10 days later. PMID- 27677876 TI - Photo-oxidized bovine pericardium in congenital cardiac surgery: single-centre experience. AB - Objectives: Dye-mediated photo-oxidation of pericardium is an alternative method to chemical treatment with glutaraldehyde for cross-linking collagen, providing biostability of the patch material while avoiding late calcification and cytotoxicity. There are few data available, on using photo-oxidation-treated pericardium, in congenital cardiac surgery. This study reports the outcomes using PhotofixTM bovine pericardium in neonates, infants, children and young adults undergoing paediatric cardiac surgery. Methods: A total of 490 patches in 383 consecutive operations (364 patients) were used in the surgical repair of congenital heart defects at our institution from October 2008 to October 2011. Recorded variables included demographic data, age at operation, primary cardiac diagnosis, associated complications and number, type and location of patches placed and patch-related reintervention. Results: Median age at operation was 5.3 years, ranging from <1 month to 56 years. The overall survival rate at late follow-up was 92%, and no deaths were related to failure of the tissue substitute. Two patients (0.5%) underwent reintervention late due to patch material failure: one for residual shunt after Rastelli repair and one for aneurysmal dilatation of a right ventricular outflow tract patch. The patch material was explanted in 8 patients at a mean of 20 months (range, 1-72 months) following implantation. Histological examination revealed mild to moderate inflammation with variable calcification. Conclusions: Photo-oxidized bovine pericardium demonstrated excellent performance when used as a patch material in cardiovascular repair in children. Its handling characteristics and biocompatibility are consistent with a wide range of applications. PMID- 27677877 TI - The association between the transfusion of small volumes of leucocyte-depleted red blood cells and outcomes in patients undergoing open-heart valve surgery. AB - Objectives: The relationship between the transfusion of red blood cell (RBC) units and outcomes in patients undergoing cardiac surgery is the subject of intense debates. In this study, we investigated the relationship between the transfusion of 1-2 leucocyte-depleted (LD) RBC units and outcomes in patients undergoing open-heart valve surgery. Methods: The investigation encompassed consecutive patients undergoing open-heart valve surgery at our institution between July 2009 and March 2015 who received no (RBC- group) or 1-2 units of LD RBC (RBC+ group). End-points were 30-day mortality (primary), the incidence of in hospital major organ dysfunctions and 1-year mortality (secondary). Propensity score (PS)-adjusted statistical analysis was used to assess the effect of RBC transfusion on end-points. Results: Thirty-day mortality rate was 0.2% (3/1485) in the RBC- group and 0.4% (6/1672) in the RBC+ group, with a PS-adjusted odds ratio (OR) for 30-day mortality of 1.00 (95% CI: 0.21-4.83;P = 0.99). The two groups showed no significant differences in PS-adjusted ORs for major complications, such as stroke, low cardiac output syndrome, thoracic wound infection and prolonged mechanical ventilation (>24 h). The PS-adjusted ORs for prolonged intensive care unit stay (>48 h) were, however, significantly higher in the RBC+ group (OR = 1.34 [95%CI: 1.04-1.72; P = 0.02]) than in the RBC- group. One-year mortality was comparable between groups (PS-adjusted hazard ratio for the RBC+ group: 0.85 [95% CI: 0.42-1.72; P = 0.65]). Conclusions: Our data do not provide evidence that in patients undergoing valve surgery with cardiopulmonary bypass, transfusion of 1-2 units of LD RBC increases operative mortality, the incidence of postoperative complications or 1-year mortality. PMID- 27677879 TI - Preoperative planning with three-dimensional reconstruction of patient's anatomy, rapid prototyping and simulation for endoscopic mitral valve repair. AB - Objectives: Mitral valve repair performed by an experienced surgeon is superior to mitral valve replacement for degenerative mitral valve disease; however, many surgeons are still deterred from adapting this procedure because of a steep learning curve. Simulation-based training and planning could improve the surgical performance and reduce the learning curve. The aim of this study was to develop a patient-specific simulation for mitral valve repair and provide a proof of concept of personalized medicine in a patient prospectively planned for mitral valve surgery. Methods: A 65-year old male with severe symptomatic mitral valve regurgitation was referred to our mitral valve heart team. On the basis of three dimensional (3D) transoesophageal echocardiography and computed tomography, 3D reconstructions of the patient's anatomy were constructed. By navigating through these reconstructions, the repair options and surgical access were chosen (minimally invasive repair). Using rapid prototyping and negative mould fabrication, we developed a process to cast a patient-specific mitral valve silicone replica for preoperative repair in a high-fidelity simulator. Results: Mitral valve and negative mould were printed in systole to capture the pathology when the valve closes. A patient-specific mitral valve silicone replica was casted and mounted in the simulator. All repair techniques could be performed in the simulator to choose the best repair strategy. As the valve was printed in systole, no special testing other than adjusting the coaptation area was required. Subsequently, the patient was operated, mitral valve pathology was validated and repair was successfully done as in the simulation. Conclusions: The patient-specific simulation and planning could be applied for surgical training, starting the (minimally invasive) mitral valve repair programme, planning of complex cases and the evaluation of new interventional techniques. The personalized medicine could be a possible pathway towards enhancing reproducibility, patient's safety and effectiveness of a complex surgical procedure. PMID- 27677878 TI - Single-port right upper lobe sleeve lobectomy for a typical carcinoid tumour. AB - Pulmonary carcinoid tumours are well-differentiated neuroendocrine tumours with indolent behaviour; complete resection offers long-term survival. When centrally located, these tumours can be treated with lung-sparing procedures. We present a case of a centrally located typical carcinoid tumour treated with a minimally invasive, right upper lobe sleeve lobectomy using a single port. PMID- 27677880 TI - Congenital absence of anterior papillary muscle of the tricuspid valve and surgical repair with artificial chordae. AB - We report the case of a 26-year old woman who underwent successful tricuspid valve repair for the absence of the anterior papillary of the tricuspid valve. Preoperative echocardiography revealed grade IV tricuspid valve regurgitation, caused by congenital absence of the anterior papillary muscle and prolapse of the anterior leaflet. Tricuspid valve repair was performed using artificial chords consisting of two polytetrafluoroethylene sutures and a concomitant ring annuloplasty. Postoperative echocardiography revealed mild tricuspid valve regurgitation. This approach represented a safe and effective technique for tricuspid valve repair in congenital absence of papillary muscle. PMID- 27677884 TI - Recurrence and graft loss after renal transplantation in adults with IgA vasculitis. AB - BACKGROUND: IgA vasculitis, a rare condition resulting in end-stage renal disease, is a small-vessel vasculitis that affects the kidney in 49-83 % of adults. The reported recurrence rate of IgA vasculitis in renal transplant recipients is 11.5-60 %, leading to graft loss in 0-50 % of these patients. However, limited data are available on recurrence and graft loss after renal transplantation. METHODS: We evaluated renal transplant recipients seen from 1987 to 2015 at the Jikei University School of Medicine and the Department of Urology, Tokyo Women's Medical University. Using a 1:2 match, 21 patients with IgA vasculitis and 42 controls were selected. The mean post-transplant follow-up was 121 +/- 69 months for IgA vasculitis and 147 +/- 66 months for the controls. RESULTS: The 15-year patient survival was 100 % in IgA vasculitis and 97.6 % in the controls (p = 0.22). The 5-, 10-, and 15-year graft survival rates were 95.2, 90.5, and 81 % in IgA vasculitis and 100, 90.5, and 88.1 % in the controls, respectively (p = 0.63). The recurrence rate was 28.6 % (6 of 21 cases) and half of them (3 of 6 cases) showed histological activity (ISKDC III). We treated them with methylprednisolone pulse therapy and/or tonsillectomy. None of the recurrence cases lost the allograft. CONCLUSION: The long-term patient and graft survival of IgA vasculitis in renal transplantation were comparable with the previous reports. The recurrence rate was 28.6 %, but none of the recurrent cases showed allograft loss in this study. We speculate that methylprednisolone pulse therapy and/or tonsillectomy prevent the progression of recurrent IgA vasculitis. PMID- 27677881 TI - Arabidopsis TH2 Encodes the Orphan Enzyme Thiamin Monophosphate Phosphatase. AB - To synthesize the cofactor thiamin diphosphate (ThDP), plants must first hydrolyze thiamin monophosphate (ThMP) to thiamin, but dedicated enzymes for this hydrolysis step were unknown and widely doubted to exist. The classical thiamin requiring th2-1 mutation in Arabidopsis thaliana was shown to reduce ThDP levels by half and to increase ThMP levels 5-fold, implying that the THIAMIN REQUIRING2 (TH2) gene product could be a dedicated ThMP phosphatase. Genomic and transcriptomic data indicated that TH2 corresponds to At5g32470, encoding a HAD (haloacid dehalogenase) family phosphatase fused to a TenA (thiamin salvage) family protein. Like the th2-1 mutant, an insertional mutant of At5g32470 accumulated ThMP, and the thiamin requirement of the th2-1 mutant was complemented by wild-type At5g32470 Complementation tests in Escherichia coli and enzyme assays with recombinant proteins confirmed that At5g32470 and its maize (Zea mays) orthologs GRMZM2G148896 and GRMZM2G078283 are ThMP-selective phosphatases whose activity resides in the HAD domain and that the At5g32470 TenA domain has the expected thiamin salvage activity. In vitro and in vivo experiments showed that alternative translation start sites direct the At5g32470 protein to the cytosol and potentially also to mitochondria. Our findings establish that plants have a dedicated ThMP phosphatase and indicate that modest (50%) ThDP depletion can produce severe deficiency symptoms. PMID- 27677885 TI - Hippocampus-associated causal network of structural covariance measuring structural damage progression in temporal lobe epilepsy. AB - In mesial temporal lobe epilepsy (mTLE), the causal relationship of morphometric alterations between hippocampus and the other regions, that is, how the hippocampal atrophy leads to progressive morphometric alterations in the epileptic network regions remains largely unclear. In this study, a causal network of structural covariance (CaSCN) was proposed to map the causal effects of hippocampal atrophy on the network-based morphometric alterations in mTLE. It was hypothesized that if cross-sectional morphometric MRI data could be attributed temporal information, for example, by sequencing the data according to disease progression information, GCA would be a feasible approach for constructing a CaSCN. Based on a large cohort of mTLE patients (n = 108), the hippocampus-associated CaSCN revealed that the hippocampus and the thalamus were prominent nodes exerting causal effects (i.e., GM reduction) on other regions and that the prefrontal cortex and cerebellum were prominent nodes being subject to causal effects. Intriguingly, compensatory increased gray matter volume in the contralateral temporal region and post cingulate cortex were also detected. The method unraveled richer information for mapping network atrophy in mTLE relative to the traditional methods of stage-specific comparisons and structured covariance network. This study provided new evidence on the network spread mechanism in terms of the causal influence of hippocampal atrophy on progressive brain structural alterations in mTLE. Hum Brain Mapp 38:753-766, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27677888 TI - A new method for self-paced peak performance testing on a treadmill. AB - PURPOSE: Self-paced maximal testing methods may be able to exploit central mediation of function-limiting fatigue and therefore have potential to generate more valid estimates of peak oxygen uptake. The aim of this study was to investigate the feasibility of a new method for self-paced peak performance testing on treadmills and to compare peak and submaximal performance outcomes with those obtained using a non-self-paced ('computer-paced') method employing predetermined speed and slope profiles. METHODS: The proposed self-paced method is based upon automatic subject positioning using feedback control together with an exercise intensity which is driven by a predetermined, individualized work rate ramp. RESULTS: Peak oxygen uptake was not significantly different for the computer-paced (CP) versus self-paced (SP) protocols: 4.38 +/- 0.48 versus 4.34 +/- 0.46 ml min-1 , P = 0.42. Likewise, there were no significant differences in the other peak and submaximal cardiopulmonary parameters, viz. peak heart rate, peak respiratory exchange ratio and the first and second ventilatory thresholds. Ramp duration for CP was longer than for SP: 494.5 +/- 71.1 versus 371.3 +/- 86.0 s, P = 0.00072. Concomitantly, the peak rate of work done against gravity was higher for CP: 264.8 +/- 40.8 versus 203.8 +/- 53.4 W, P = 0.0021. CONCLUSIONS: The self-paced approach was found to be feasible for estimation of the principal performance outcomes: the method was technically implementable, it was acceptable to the subjects and it showed good responsiveness. Further investigation of the self-paced method, with adjustment of the target ramp-phase duration or modification of the work-rate calculation equations, is warranted. PMID- 27677886 TI - Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population. AB - PURPOSE: Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3 [18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. PROCEDURES: xC- transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT. RESULTS: xC- transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT. CONCLUSIONS: [18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine. PMID- 27677887 TI - Multimodal Genetic Approach for Molecular Imaging of Vasculature in a Mouse Model of Melanoma. AB - PURPOSE: In this study, we evaluated a genetic approach for in vivo multimodal molecular imaging of vasculature in a mouse model of melanoma. PROCEDURES: We used a novel transgenic mouse, Ts-Biotag, that genetically biotinylates vascular endothelial cells. After inoculating these mice with B16 melanoma cells, we selectively targeted endothelial cells with (strept)avidinated contrast agents to achieve multimodal contrast enhancement of Tie2-expressing blood vessels during tumor progression. RESULTS: This genetic targeting system provided selective labeling of tumor vasculature and showed in vivo binding of avidinated probes with high specificity and sensitivity using microscopy, near infrared, ultrasound, and magnetic resonance imaging. We further demonstrated the feasibility of conducting longitudinal three-dimensional (3D) targeted imaging studies to dynamically assess changes in vascular Tie2 from early to advanced tumor stages. CONCLUSIONS: Our results validated the Ts-Biotag mouse as a multimodal targeted imaging system with the potential to provide spatio-temporal information about dynamic changes in vasculature during tumor progression. PMID- 27677889 TI - Emergence of gamma motor activity in an artificial neural network model of the corticospinal system. AB - Muscle spindle discharge during active movement is a function of mechanical and neural parameters. Muscle length changes (and their derivatives) represent its primary mechanical, fusimotor drive its neural component. However, neither the action nor the function of fusimotor and in particular of gamma-drive, have been clearly established, since gamma-motor activity during voluntary, non-locomotor movements remains largely unknown. Here, using a computational approach, we explored whether gamma-drive emerges in an artificial neural network model of the corticospinal system linked to a biomechanical antagonist wrist simulator. The wrist simulator included length-sensitive and gamma-drive-dependent type Ia and type II muscle spindle activity. Network activity and connectivity were derived by a gradient descent algorithm to generate reciprocal, known target alpha-motor unit activity during wrist flexion-extension (F/E) movements. Two tasks were simulated: an alternating F/E task and a slow F/E tracking task. Emergence of gamma-motor activity in the alternating F/E network was a function of alpha-motor unit drive: if muscle afferent (together with supraspinal) input was required for driving alpha-motor units, then gamma-drive emerged in the form of alpha-gamma coactivation, as predicted by empirical studies. In the slow F/E tracking network, gamma-drive emerged in the form of alpha-gamma dissociation and provided critical, bidirectional muscle afferent activity to the cortical network, containing known bidirectional target units. The model thus demonstrates the complementary aspects of spindle output and hence gamma-drive: i) muscle spindle activity as a driving force of alpha-motor unit activity, and ii) afferent activity providing continuous sensory information, both of which crucially depend on gamma-drive. PMID- 27677890 TI - Review of knee arthroscopic practice and coding at a major metropolitan centre. AB - BACKGROUND: Arthroscopic knee surgery has been a topic of significant controversy in recent orthopaedic literature. Multiple studies have used administrative (Victorian Admitted Episodes Dataset and Centre for Health Record Linkage) data to identify trends in practice. This study explored the usage and reporting of arthroscopic knee surgery by conducting a detailed audit at a major Victorian public hospital. METHODS: A database of orthopaedic procedures at St Vincent's Hospital Melbourne was used to retrospectively identify cases of knee arthroscopy from 1 December 2011 to 1 April 2014. Procedures were categorized as diagnostic or interventional, and native and prosthetic joints were analysed separately. Procedure codes were reviewed by comparing a registrar, auditor and hospital coders for agreement. RESULTS: Of the 401 cases for analysis, 375 were conducted in native knees and 26 in prosthetic joints. Of native knees, 369 (98.4%) were considered interventional. The majority of these were conducted for meniscal pathology (n = 263, 70.1%), osteoarthritis (OA) (n = 25, 6.7%) and infection (n = 28, 7.6%). Comparison of codes assigned by different parties were found to be between 57% (k = 0.324) and 70% (k = 0.572) agreement, but not statistically significant. CONCLUSIONS: In this study, the most common indication for arthroscopy was meniscal pathology. Arthroscopy was rarely performed for OA in the absence of meniscal pathology. Diagnostic arthroscopy was rarely performed in the native knee, and fair to moderate agreement existed between parties in assigning Medicare Benefits Schedule procedure codes. PMID- 27677891 TI - Vibrational Response of Methylammonium Lead Iodide: From Cation Dynamics to Phonon-Phonon Interactions. AB - The dynamic evolution of the vibrational interactions in the prototypical CH3 NH3 PbI3 was studied through a comprehensive experimental and theoretical investigation with a focus on the interactions between the organic cations and the inorganic cage. To date, no clear picture has emerged on the critical and fundamental interactions between the two perovskite components, despite the relevance of phonons to the electronic properties of several classes of perovskites. For the first time, we have monitored the IR and nonresonant Raman response in the broad frequency range 30-3400 cm-1 and in the temperature interval 80-360 K. Strong changes in the energies of different vibrational modes with temperature are observed and examined in the framework of phonon-phonon interactions considering a significant anharmonic contribution to the phonon relaxation process. The vibrational relaxation of the bending modes and their reorientation activation energies identify that such mechanisms are governed by medium-to-strong hydrogen bonds in the orthorhombic phase; however, any ferroelectric ordering in the orthorhombic phase is governed mostly by dipole interactions. These changes imply that charge localization mechanisms play a primary role, and our study enriches the fundamental knowledge of phonon interactions and charge transport in CH3 NH3 PbI3 for the further development of optoelectronic applications. PMID- 27677893 TI - Characterization of the Cutaneous Bacterial Communities of Two Giant Salamander Subspecies. AB - Pathogens currently threaten the existence of many amphibian species. In efforts to combat global declines, researchers have characterized the amphibian cutaneous microbiome as a resource for disease management. Characterization of microbial communities has become useful in studying the links between organismal health and the host microbiome. Hellbender salamanders (Cryptobranchus alleganiensis) provide an ideal system to explore the cutaneous microbiome as this species requires extensive conservation management across its range. In addition, the Ozark hellbender subspecies (Cryptobranchus alleganiensis bishopi) exhibits chronic wounds hypothesized to be caused by bacterial infections, whereas the eastern hellbender (Cryptobranchus alleganiensis alleganiensis) does not. We assessed the cutaneous bacterial microbiome of both subspecies at two locations in the state of Missouri, USA. Through 16S rRNA gene-based amplicon sequencing, we detected more than 1000 distinct operational taxonomic units (OTUs) in the cutaneous and environmental bacterial microbiome. Phylogenetic and abundance based dissimilarity matrices identified differences in the bacterial communities between the two subspecies, but only the abundance-based dissimilarity matrix identified differences between wounds and healthy skin on Ozark hellbenders. The higher abundance of OTUs on Ozark wounds suggests that commensal bacteria present on the skin and environment may be opportunistically colonizing the wounds. This brief exploration of the hellbender cutaneous bacterial microbiome provides foundational support for future studies seeking to understand the hellbender cutaneous bacterial microbiome and the role of the bacterial microbiota on chronic wounds of Ozark hellbenders. PMID- 27677892 TI - Impact of Cropping Systems, Soil Inoculum, and Plant Species Identity on Soil Bacterial Community Structure. AB - Farming practices affect the soil microbial community, which in turn impacts crop growth and crop-weed interactions. This study assessed the modification of soil bacterial community structure by organic or conventional cropping systems, weed species identity [Amaranthus retroflexus L. (redroot pigweed) or Avena fatua L. (wild oat)], and living or sterilized inoculum. Soil from eight paired USDA certified organic and conventional farms in north-central Montana was used as living or autoclave-sterilized inoculant into steam-pasteurized potting soil, planted with Am. retroflexus or Av. fatua and grown for two consecutive 8-week periods to condition soil nutrients and biota. Subsequently, the V3-V4 regions of the microbial 16S rRNA gene were sequenced by Illumina MiSeq. Treatments clustered significantly, with living or sterilized inoculum being the strongest delineating factor, followed by organic or conventional cropping system, then individual farm. Living inoculum-treated soil had greater species richness and was more diverse than sterile inoculum-treated soil (observed OTUs, Chao, inverse Simpson, Shannon, P < 0.001) and had more discriminant taxa delineating groups (linear discriminant analysis). Living inoculum soil contained more Chloroflexi and Acidobacteria, while the sterile inoculum soil had more Bacteroidetes, Firmicutes, Gemmatimonadetes, and Verrucomicrobia. Organically farmed inoculum treated soil had greater species richness, more diversity (observed OTUs, Chao, Shannon, P < 0.05), and more discriminant taxa than conventionally farmed inoculum-treated soil. Cyanobacteria were higher in pots growing Am. retroflexus, regardless of inoculum type, for three of the four organic farms. Results highlight the potential of cropping systems and species identity to modify soil bacterial communities, subsequently modifying plant growth and crop-weed competition. PMID- 27677896 TI - When the Spirit Is Willing, but the Flesh Is Weak: Developmental Differences in Judgments About Inner Moral Conflict. AB - Sometimes it is easy to do the right thing. But often, people act morally only after overcoming competing immoral desires. How does learning about someone's inner moral conflict influence children's and adults' moral judgments about that person? Across four studies, we discovered a striking developmental difference: When the outcome is held constant, 3- to 8-year-old children judge someone who does the right thing without experiencing immoral desires to be morally superior to someone who does the right thing through overcoming conflicting desires-but adults have the opposite intuition. This developmental difference also occurs for judgments of immoral actors: Three- to 5-year-olds again prefer the person who is not conflicted, whereas older children and adults judge that someone who struggles with the decision is morally superior. Our findings suggest that children may begin with the view that inner moral conflict is inherently negative, but, with development, come to value the exercise of willpower and self control. PMID- 27677895 TI - Integrating Out-of-Office Blood Pressure in the Diagnosis and Management of Hypertension. AB - Guidelines for the diagnosis and monitoring of hypertension were historically based on in-office blood pressure measurements. However, the US Preventive Services Task Force recently expanded their recommendations on screening for hypertension to include out-of-office blood pressure measurements to confirm the diagnosis of hypertension. Out-of-office blood pressure monitoring modalities, including ambulatory blood pressure monitoring and home blood pressure monitoring, are important tools in distinguishing between normotension, masked hypertension, white-coat hypertension, and sustained (including uncontrolled or drug-resistant) hypertension. Compared to in-office readings, out-of-office blood pressures are a greater predictor of renal and cardiac morbidity and mortality. There are multiple barriers to the implementation of out-of-office blood pressure monitoring which need to be overcome in order to promote more widespread use of these modalities. PMID- 27677894 TI - Cutaneous Bacterial Communities of a Poisonous Salamander: a Perspective from Life Stages, Body Parts and Environmental Conditions. AB - Amphibian skin provides a habitat for bacterial communities in its mucus. Understanding the structure and function of this "mucosome" in the European fire salamander (Salamandra salamandra) is critical in the context of novel emerging pathogenic diseases. We compare the cutaneous bacterial communities of this species using amplicon-based sequencing of the 16S rRNA V4 region. Across 290 samples, over 4000 OTUs were identified, four of them consistently present in all samples. Larvae and post-metamorphs exhibited distinct cutaneous microbial communities. In adults, the parotoid gland surface had a community structure different from the head, dorsum, flanks and ventral side. Larvae from streams had higher phylogenetic diversity than those found in ponds. Their bacterial community structure also differed; species of Burkholderiaceae, Comamonadaceae, Methylophilaceae and Sphingomonadaceae were more abundant in pond larvae, possibly related to differences in factors like desiccation and decomposition rate in this environment. The observed differences in the cutaneous bacterial community among stages, body parts and habitats of fire salamanders suggest that both host and external factors shape these microbiota. We hypothesize that the variation in cutaneous bacterial communities might contribute to variation in pathogen susceptibility among individual salamanders. PMID- 27677897 TI - Impaired Velocity Processing Reveals an Agnosia for Motion in Depth. AB - Many individuals with normal visual acuity are unable to discriminate the direction of 3-D motion in a portion of their visual field, a deficit previously referred to as a stereomotion scotoma. The origin of this visual deficit has remained unclear. We hypothesized that the impairment is due to a failure in the processing of one of the two binocular cues to motion in depth: changes in binocular disparity over time or interocular velocity differences. We isolated the contributions of these two cues and found that sensitivity to interocular velocity differences, but not changes in binocular disparity, varied systematically with observers' ability to judge motion direction. We therefore conclude that the inability to interpret motion in depth is due to a failure in the neural mechanisms that combine velocity signals from the two eyes. Given these results, we argue that the deficit should be considered a prevalent but previously unrecognized agnosia specific to the perception of visual motion. PMID- 27677898 TI - Multitargeting Gene Delivery Systems for Enhancing the Transfection of Endothelial Cells. AB - Gene therapy demonstrates promising prospects on cardiovascular diseases. However, nonviral gene delivery system has relatively low transfection efficiency, especially for endothelial cells (ECs). Herein, typical cell penetrating peptide (TAT), nuclear localization signals (NLSs), and REDV functional peptide have been used to prepare multitargeting complexes. These complexes exhibit higher transfection efficiency owing to the targeting sequences of REDV and NLSs as well as the cell-penetrating function of TAT. The multifunction of the complexes provides high cell uptake, endo/lysosomal escape, and nucleus accumulation of the encapsulated DNA. Thus these multitargeting complexes can provide a potential platform for gene delivery, especially for EC transfection. PMID- 27677899 TI - Coexistence of multiple minor states of fatty acid binding protein and their functional relevance. AB - Proteins are dynamic over a wide range of timescales, but determining the number of distinct dynamic processes and identifying functionally relevant dynamics are still challenging. Here we present the study on human intestinal fatty acid binding protein (hIFABP) using a novel analysis of 15N relaxation dispersion (RD) and chemical shift saturation transfer (CEST) experiments. Through combined analysis of the two types of experiments, we found that hIFABP exists in a four state equilibrium in which three minor states interconvert directly with the major state. According to conversion rates from the major "closed" state to minor states, these minor states are irrelevant to the function of fatty acid transport. Based on chemical shifts of the minor states which could not be determined from RD data alone but were extracted from a combined analysis of RD and CEST data, we found that all the minor states are native-like. This conclusion is further supported by hydrogen-deuterium exchange experiments. Direct conversions between the native state and native-like intermediate states may suggest parallel multitrack unfolding/folding pathways of hIFABP. Moreover, hydrogen-deuterium exchange data indicate the existence of another locally unfolded minor state that is relevant to the fatty acid entry process. PMID- 27677900 TI - A mathematical algorithm for quantification of CT image noise. AB - Quantification of computed tomography (CT) noise helps in determination of radiation dosage requirements for adequate image quality. Clinical methods used include calculation of the standard deviation (SD) of a selected region of interest (ROI). In industry, wavelet decomposition has been used for image compression while removing high-frequency noise. We evaluated a cohort of 74 consecutive patients referred for coronary artery calcium scoring and quantitated noise within a 16*16 ROI in the ascending aorta using the traditional SD method and also using a two-dimensional dyadic wavelet decomposition method. Clinically, noise has been shown to be proportional to patient weight and also body mass index (BMI), which is a derived value from height and weight. Noise for both methods was plotted against patient parameters of height, weight, waist circumference and calculated BMI. A regression line was calculated and coefficient of determination (CoD) calculated for each. The CoD was better for height, weight, and waist circumference using the wavelet method as compared to the traditional SD method. The wavelet method of quantification of image noise may be an improved method as compared to the SD method. This method could help further refine an imaging system's determination of radiation dosage requirements to obtain a satisfactory quality image. PMID- 27677901 TI - Reduced tract integrity of the model for social communication is a neural substrate of social communication deficits in autism spectrum disorder. AB - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with social communication deficits as one of the core symptoms. Recently, a five-level model for the social communication has been proposed in which white matter tracts corresponding to each level of the model are identified. Given that the model for social communication subserves social language functions, we hypothesized that the tract integrity of the model for social communication may be reduced in ASD, and the reduction may be related to social communication deficits. METHODS: Sixty two right-handed boys with ASD and 55 typically developing (TD) boys received clinical evaluations, intelligence tests, the Social Communication Questionnaire (SCQ), and MRI scans. Generalized fractional anisotropy (GFA) was measured by diffusion spectrum imaging to indicate the microstructural integrity of the tracts for each level of the social communication model. Group difference in the tract integrity and its relationship with the SCQ subscales of social communication and social interaction were investigated. RESULTS: We found that the GFA values of the superior longitudinal fasciculus III (SLF III, level 1) and the frontal aslant tracts (FAT, level 2) were decreased in ASD compared to TD. Moreover, the GFA values of the SLF III and the FAT were associated with the social interaction subscale in ASD. CONCLUSIONS: The tract integrity of the model for social communication is reduced in ASD, and the reduction is associated with impaired social interaction. Our results support that reduced tract integrity of the model for social communication might be a neural substrate of social communication deficits in ASD. PMID- 27677902 TI - Endemic impact of human T cell leukemia virus type 1 screening in bone allografts. AB - Allograft bone is a widely used as a convenient tool for reconstructing massive bone defects in orthopedic surgery. However, allografts are associated with the risk of viral disease transmission. One of the viruses transmitted in this manner is human T-lymphotropic virus type 1 (HTLV-1), which is found worldwide but is unevenly distributed. The southwestern parts of Japan are a highly endemic for HTLV-1. We investigated the HTLV-1 seroprevalence in candidate allograft donors at the regional bone bank in Kagoshima, Japan during its first 5 years of service. Between 2008 and 2012, we collected 282 femoral heads at the Kagoshima regional bone bank from living donors with osteoarthritis of the hip joint. Among the 282 candidate donors, 32 donors (11.3 %) were seropositive for anti-HTLV-1 antibody; notably, this prevalence is higher than that reported for blood donors in this area. Additionally, to determine if HTLV-1 genes are detectable after processing, we examined the bone marrow of the femoral heads from seropositive donors by conducting PCR assays. Our results confirm the existence of viral genes following the heat treatment processing of the femoral heads. Therefore, it is important to inactivate a virus completely by heat-treatment. Together, our findings highlight the importance of HTLV-1 screening at bone banks, particularly in HTLV-1-endemic areas such as southwest Japan. PMID- 27677904 TI - Estimation bias resulting from sparse data: response to comments by Zhang and Ren. PMID- 27677903 TI - Cytotoxicity testing of a polyurethane nanofiber membrane modified with chitosan/beta-cyclodextrin/berberine suitable for wound dressing application: evaluation of biocompatibility. AB - In this study we evaluated the biocompatibility of a modified polyurethane nanofiber membrane on a polypropylene spunbond substrate. This material was treated with plasma using diffuse coplanar surface barrier discharge, and subsequent modification was done by continuous spraying of a biologically active chitosan solution (CHIT) containing an inclusion complex of beta-cyclodextrin (beta-CD) encapsulating berberine (BRB). Biocompatibility was evaluated using several in vitro assays. Human dermal fibroblasts (HDFs) and 3T3 murine fibroblasts were used as biological models. The results of these assays showed that a polyurethane nanofiber membrane modified by CHIT/beta-CD/BRB appears to be non-toxic and biocompatible; potentially, it could be used as a wound dressing after further testing. PMID- 27677905 TI - Estimation bias resulting from sparse data. PMID- 27677907 TI - Mechanics in human fibroblasts and progeria: Lamin A mutation E145K results in stiffening of nuclei. AB - The lamina is a filamentous meshwork beneath the inner nuclear membrane that confers mechanical stability to nuclei. The E145K mutation in lamin A causes Hutchinson-Gilford progeria syndrome (HGPS). It affects lamin filament assembly and induces profound changes in the nuclear architecture. Expression of wild-type and E145K lamin A in Xenopus oocytes followed by atomic force microscopy (AFM) probing of isolated oocyte nuclei has shown significant changes in the mechanical properties of the lamina. Nuclei of oocytes expressing E145K lamin A are stiffer than those expressing wild-type lamin A. Here we present mechanical measurements by AFM on dermal fibroblasts obtained from a 4-year-old progeria patient bearing the E145K lamin A mutation and compared it to fibroblasts obtained from 2 healthy donors of 10 and 61 years of age, respectively. The abnormal shape of nuclei expressing E145K lamin A was analyzed by fluorescence microscopy. Lamina thickness was measured using electron micrographs. Fluorescence microscopy showed alterations in the actin network of progeria cells. AFM probing of whole dermal fibroblasts did not demonstrate significant differences in the elastic moduli of nuclear and cytoplasmic cell regions. In contrast, AFM measurements of isolated nuclei showed that nuclei of progeria and old person's cells are significantly stiffer than those of the young person, indicating that the process of aging, be it natural or abnormal, increases nuclear stiffness. Our results corroborate AFM data obtained using Xenopus oocyte nuclei and prove that the presence of E145K lamin A abnormally increases nuclear stiffness. PMID- 27677906 TI - Y90 -Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05). AB - Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90 -Ibritumomab tiuxetan (Y90 -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y90 -IT as a conditioning regimen for patients >=65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y90 -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m2 ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y90 -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity. PMID- 27677909 TI - Risk of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Exogenous Vasopressin Infusion. AB - BACKGROUND: Vasopressin is one of the vasopressors used to augment blood pressure in subarachnoid hemorrhage (SAH) patients with clinically significant vasospasm. The purpose of the present study was to determine whether the administration of vasopressin to a population of SAH patients was an independent predictor of developing hyponatremia. METHODS: A retrospective review on the health records of 106 patients admitted to the University of Alberta Hospital Neurosciences ICU, Edmonton AB, Canada, with SAH from June 2013 to December 2015 was conducted. Serum sodium changes in patients receiving vasoactive drugs were compared. In addition, independent predictors for hyponatremia (Na < 135 mmol/L) were determined using a multivariate logistic regression model. RESULTS: Patients treated with vasopressin in addition to other vasoactive drugs had significantly higher sodium changes compared to those treated with other vasoactive drugs (-4.7 +/- 6 vs -0.1 +/- 2.4 mmol/L, respectively, p value 0.001). Hyponatremia occurred in 14 patients (70 %) treated with vasopressin, 10 patients (44 %) treated with vasoactive drugs other than vasopressin (p value 0.081), and 24 patients (38 %) who did not receive any vasoactive drug (p value 0.013). In multivariate logistic regression analysis, when adjusting for disease severity, age, sex, aneurysm location, and treatment, vasopressin was associated with hyponatremia (OR 3.58, 95 % CI, 1.02-12.5, p value 0.046). CONCLUSIONS: The results of the present study suggest that hyponatremia may be more common in SAH patients treated with exogenous vasopressin compared to those who did not receive it. Serum sodium should be monitored closely when vasopressin is being used in the SAH population. Further studies are needed to confirm the effect of exogenous vasopressin on serum sodium levels in SAH populations. PMID- 27677910 TI - Cytomegalovirus sinusitis complicated by orbital apex syndrome in an immunocompromised host. AB - Sinusitis in immunocompromised patients can be caused by a wide variety of pathogens, primarily bacterial and fungal in nature. Tissue invasion can extend into the orbital apex and result in ophthalmoplegia and blindness. We report the first histologically proven case, to our knowledge, caused by cytomegalovirus infection. PMID- 27677908 TI - ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI. AB - OBJECTIVE: Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (ABCC8) on the development of CE. We hypothesize that ABCC8 single nucleotide polymorphisms (SNPs) are predictive of CE. METHODS: DNA was extracted from 385 patients. SNPs in ABCC8 were genotyped using the Human Core Exome v1.2 (Illumina). CE measurements included acute CT edema, mean and peak intracranial pressure (ICP), and need for decompressive craniotomy. RESULTS: Fourteen SNPs with minor allele frequency >0.2 were identified. Four SNPS rs2283261, rs3819521, rs2283258, and rs1799857 were associated with CE measures. In multiple regression models, homozygote-variant genotypes in rs2283261, rs3819521, and rs2283258 had increased odds of CT edema (OR 2.45, p = 0.007; OR 2.95, p = 0.025; OR 3.00, p = 0.013), had higher mean (beta = 3.13, p = 0.000; beta = 2.95, p = 0.005; beta = 3.20, p = 0.008), and peak ICP (beta = 8.00, p = 0.001; beta = 7.64, p = 0.007; beta = 6.89, p = 0.034). The homozygote wild-type genotype of rs1799857 had decreased odds of decompressive craniotomy (OR 0.47, p = 0.004). CONCLUSIONS: This is the first report assessing the impact of ABCC8 genetic variability on CE development in TBI. Minor allele ABCC8 SNP genotypes had increased risk of CE, while major SNP alleles were protective-potentially suggesting an evolutionary advantage. These findings could guide risk stratification, treatment responders, and the development of novel targeted or gene-based therapies against CE in TBI and other neurological disorders. PMID- 27677911 TI - Induction, management, and complications of streptozotocin-induced diabetes mellitus in rhesus monkeys. AB - BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of beta cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months. METHODS: Streptozotocin (immediately dissolved in normal saline, 110 mg/kg) was slowly infused via central catheter for 10 minutes in 22 rhesus monkeys. Clinical signs, complete blood count and blood chemistry were monitored to evaluate toxicity for 1 week after STZ injection. Monkey basal C-peptides were measured and intravenous glucose tolerance test was performed to confirm complete induction of DM. Exogenous insulin was subcutaneously injected to maintain blood glucose in diabetic rhesus monkeys and the complications were recorded while in insulin treatment. RESULTS: Severe salivation and vomiting were observed within 1 hour after STZ injection in 22 rhesus monkeys. One monkey died at 6 hours after STZ injection and the reason for the death was unknown. Pancreatitis was noticed in one monkey after STZ injection, but the monkey recovered after 5 days by medical treatment. Serum total protein and albumin decreased whereas the parameters for the liver function such as aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly increased (P<.05) after STZ injection, but they were resolved within 1 week. Azotemia was not observed. Monkey fasting C peptide levels after STZ injection were <0.1 ng/mL in 18 rhesus monkeys, but 0.34, 0.22, 0.16 ng/mL in three monkeys, respectively. The value of daily insulin requirement was 0.92+/-0.26IU/kg/d (range=0.45-1.29) in the monkeys. Diabetic ketoacidosis was observed in one rhesus monkeys, but the monkey recovered after 24 hours by fluid and insulin treatment. CONCLUSIONS: Streptozotocin was effective for inducing DM in rhesus monkeys, but various adverse effects such as pancreatitis, liver toxicity or death were observed. Therefore, careful and suitable medical managements should be implemented to eliminate the risks of mortality and severe adverse effects. PMID- 27677912 TI - 3D Printing of Emulsions and Foams into Hierarchical Porous Ceramics. AB - Bulk hierarchical porous ceramics with unprecedented strength-to-weight ratio and tunable pore sizes across three different length scales are printed by direct ink writing. Such an extrusion-based process relies on the formulation of inks in the form of particle-stabilized emulsions and foams that are sufficiently stable to resist coalescence during printing. PMID- 27677913 TI - A Review of the Acute Effects and Long-Term Adaptations of Single- and Multi Joint Exercises during Resistance Training. AB - Resistance exercises can be considered to be multi-joint (MJ) or single-joint (SJ) in nature. Many strength coaches, trainers, and trainees believe that adding SJ exercises to a resistance training (RT) program may be required to optimize muscular size and strength. However, given that lack of time is a frequently cited barrier to exercise adoption, the time commitment resulting from these recommendations may not be convenient for many people. Therefore, it is important to find strategies that reduce the time commitment without negatively affecting results. The aim of this review was to analyze and discuss the present body of literature considering the acute responses to and long-term adaptations resulting from SJ and MJ exercise selection. Studies were deemed eligible for inclusion if they were experimental studies comparing the effects of MJ, SJ, or MJ + SJ on dependent variables; studies were excluded if they were reviews or abstracts only, if they involved clinical populations or persons with articular or musculoskeletal problems, or if the RT intervention was confounded by other factors. Taking these factors into account, a total of 23 studies were included. For the upper and lower limbs, analysis of surface electromyographic (sEMG) activation suggests that there are no differences between SJ and MJ exercises when comparing the prime movers. However, evidence is contrasting when considering the trunk extensor musculature. Only one study directly compared the effects of MJ and SJ on muscle recovery and the results suggest that SJ exercises resulted in increased muscle fatigue and soreness. Long-term studies comparing increases in muscle size and strength in the upper limbs reported no difference between SJ and MJ exercises and no additional effects when SJ exercises were included in an MJ exercise program. For the lumbar extensors, the studies reviewed tend to support the view that this muscle group may benefit from SJ exercise. People performing RT may not need to include SJ exercises in their program to obtain equivalent results in terms of muscle activation and long-term adaptations such as hypertrophy and strength. SJ exercises may only be necessary to strengthen lumbar extensors and to correct muscular imbalances. PMID- 27677914 TI - Effect of Glycemic Index of a Pre-exercise Meal on Endurance Exercise Performance: A Systematic Review and Meta-analysis. AB - BACKGROUND: Low glycemic index (GI) pre-exercise meals may enhance endurance performance by maintaining euglycemia and altering fuel utilization. However, evidence for performance benefits is equivocal. OBJECTIVE: To evaluate the effect of a low GI (LGI) versus a high GI (HGI) pre-exercise meal on endurance performance using meta-analyses. METHODS: Data sources included MEDLINE, SPORTDiscus, AUSPORT, AusportMed, Web of Science, and Scopus. Eligibility criteria were randomized, crossover trials with an endurance exercise (>=60 min) component, e.g., time trial (TT), time to exhaustion (TTE) test, or submaximal bout followed by TT or TTE. Participants were healthy, active individuals aged >=16 years. Interventions included a LGI (<=55) and HGI (>=70) meal ingested 30 240 min before exercise. Study quality was assessed using an adapted version of the validated Downs and Black tool. Effect size (ES) and 95 % confidence interval were calculated for each study and pooled according to performance test type and whether exogenous carbohydrate (CHO) was given during exercise. Potential effect modifiers including exercise duration, pre-exercise meal timing, glycemic load (GL), and fitness were assessed using meta-regression. RESULTS: The search netted 3431 citations with 19 studies eligible for inclusion (totaling 188 participants; 91 % male; VO2max: >50 ml/kg/min). Meals with 0.18-2 g CHO/kg body mass, and a mean GI and glycemic load of 82 (GL: 72) and 35 (GL: 32) for HGI and LGI, respectively, were given between 30 and 210 min before exercise. All test types without CHO ingestion during exercise showed slightly improved performance with LGI, but no significant pooled effects were observed (ES: -0.17 to -0.36; p > 0.05). Studies where exogenous CHO was ingested during exercise showed conflicting results (ES: -0.67 to 0.11; p = 0.04 to 0.94). No significant relationship was observed with any of the effect modifiers (p > 0.05). No consistent metabolic responses (glucose, insulin, lactate, respiratory exchange ratio) during exercise were observed with either meal type. LIMITATIONS: There were small numbers of studies within each exercise testing protocol and limited statistical power within studies. Pre-exercise meal timing, GL, meal composition and participant fitness varied across studies, limiting the capacity to assess the influence of these factors on study outcomes. CONCLUSION: There was no clear benefit of consuming a LGI pre-exercise meal for endurance performance regardless of carbohydrate ingestion during exercise. PMID- 27677915 TI - Training to Fatigue: The Answer for Standardization When Assessing Muscle Hypertrophy? AB - Studies examining resistance training are of importance given that increasing or maintaining muscle mass aids in the prevention or attenuation of chronic disease. Within the literature, it is common practice to administer a set number of target repetitions to be completed by all individuals (i.e. 3 sets of 10) while setting the load relative to each individual's predetermined strength level (usually a one-repetition maximum). This is done under the assumption that all individuals are receiving a similar stimulus upon completing the protocol, but this does not take into account individual variability with regard to how fatiguing the protocol actually is. Another limitation that exists within the current literature is the reporting of exercise volume in absolute or relative terms that are not truly replicable as they are both load-dependent and will differ based on the number of repetitions individuals can complete at a given relative load. Given that the level of fatigue caused by an exercise protocol is a good indicator of its hypertrophic potential, the most appropriate way to ensure all individuals are given a common stimulus is to prescribe exercise to volitional fatigue. While some authors commonly employ this practice, others still prescribe an arbitrary number of repetitions, which may lead to unfair comparisons between exercise protocols. The purpose of this opinion piece is to provide evidence for the need to standardize studies examining muscle hypertrophy. In our opinion, one way in which this can be accomplished is by prescribing all sets to volitional fatigue. PMID- 27677918 TI - US doctors recommend continuous glucose monitoring for patients with type 1 diabetes. PMID- 27677916 TI - Biological Therapies in Regenerative Sports Medicine. AB - Regenerative medicine seeks to harness the potential of cell biology for tissue replacement therapies, which will restore lost tissue functionality. Controlling and enhancing tissue healing is not just a matter of cells, but also of molecules and mechanical forces. We first describe the main biological technologies to boost musculoskeletal healing, including bone marrow and subcutaneous fat-derived regenerative products, as well as platelet-rich plasma and conditioned media. We provide some information describing possible mechanisms of action. We performed a literature search up to January 2016 searching for clinical outcomes following the use of cell therapies for sports conditions, tendons, and joints. The safety and efficacy of cell therapies for tendon conditions was examined in nine studies involving undifferentiated and differentiated (skin fibroblasts, tenocytes) cells. A total of 54 studies investigated the effects of mesenchymal stem-cell (MSC) products for joint conditions including anterior cruciate ligament, meniscus, and chondral lesions as well as osteoarthritis. In 22 studies, cellular products were injected intra-articularly, whereas in 32 studies MSC products were implanted during surgical/arthroscopic procedures. The heterogeneity of clinical conditions, cellular products, and approaches for delivery/implantation make comparability difficult. MSC products appear safe in the short- and mid-term, but studies with a long follow-up are scarce. Although the current number of randomized clinical studies is low, stem-cell products may have therapeutic potential. However, these regenerative technologies still need to be optimized. PMID- 27677919 TI - Smart Carbon Nanotubes with Laser-Controlled Behavior in Gene Delivery and Therapy through a Non-Digestive Trafficking Pathway. AB - Near-infrared (NIR) laser-controlled gene delivery presents some benefits in gene therapy, inducing enhanced gene transfection efficiency. In this study, a "photothermal transfection" agent is obtained by wrapping poly(ethylenimine) cholesterol derivatives (PEI-Chol) around single-walled carbon nanotubes (SWNTs). The PEI-Chol modified SWNTs (PCS) are effective in compressing DNA molecules and protecting them from DNaseI degradation. Compared to the complexes formed by PEI with DNA (PEI/DNA), complexes of PCS and DNA that are formed (PCS/DNA) exhibit a little lower toxicity to HEK293 and HeLa cells under the same PEI molecule weight and weight ratios. Notably, caveolae-mediated cellular uptake of PCS/DNA occurs, which results in a safer intracellular transport of the gene due to the decreased lysosomal degradation in comparison with that of PEI/DNA whose internalization mainly depends on clathrin rather than caveolae. Furthermore, unlike PEI/DNA, PCS/DNA exhibits a photothermal conversion ability, which promotes DNA release from PCS under NIR laser irradiation. The NIR laser-mediated photothermal transfection of PCS10K /plasmid TP53 (pTP53) results in more apoptosis and necrosis of HeLa cells in vitro than other groups, and achieves a higher tumor growth inhibition in vivo than naked pTP53, PEI25K /pTP53, and PCS10K /pTP53 alone. The enhanced transfection efficiency of PCS/DNA can be attributed to more efficient DNA internalization into the tumor cells, promotes detachment of DNA from PCS under the mediation of NIR laser and higher DNA stability in the cells due to caveolae-mediated cellular uptake of the complexes. PMID- 27677917 TI - Training Load and Fatigue Marker Associations with Injury and Illness: A Systematic Review of Longitudinal Studies. AB - BACKGROUND: Coaches, sport scientists, clinicians and medical personnel face a constant challenge to prescribe sufficient training load to produce training adaption while minimising fatigue, performance inhibition and risk of injury/illness. OBJECTIVE: The aim of this review was to investigate the relationship between injury and illness and longitudinal training load and fatigue markers in sporting populations. METHODS: Systematic searches of the Web of Science and PubMed online databases to August 2015 were conducted for articles reporting relationships between training load/fatigue measures and injury/illness in athlete populations. RESULTS: From the initial 5943 articles identified, 2863 duplicates were removed, followed by a further 2833 articles from title and abstract selection. Manual searching of the reference lists of the remaining 247 articles, together with use of the Google Scholar 'cited by' tool, yielded 205 extra articles deemed worthy of assessment. Sixty-eight studies were subsequently selected for inclusion in this study, of which 45 investigated injury only, 17 investigated illness only, and 6 investigated both injury and illness. This systematic review highlighted a number of key findings, including disparity within the literature regarding the use of various terminologies such as training load, fatigue, injury and illness. Athletes are at an increased risk of injury/illness at key stages in their training and competition, including periods of training load intensification and periods of accumulated training loads. CONCLUSIONS: Further investigation of individual athlete characteristics is required due to their impact on internal training load and, therefore, susceptibility to injury/illness. PMID- 27677920 TI - Improved Measurement of Brain Phenylalanine and Tyrosine Related to Neuropsychological Functioning in Phenylketonuria. AB - INTRODUCTION: Researchers hypothesized that in phenylketonuria (PKU) high brain phenylalanine (Phe) levels and low brain tyrosine (Tyr) levels affect neuropsychological functioning. However, traditional magnetic resonance spectroscopy (MRS) yielded uncertain results of brain Phe and could not adequately measure brain Tyr. This pilot study examined the potential of correlated spectroscopy (COSY) to quantify these biomarkers and explain variability in neuropsychological functioning. METHODS: Nine adults with early treated classic PKU received magnetic resonance imaging (MRI) with COSY and a battery of neuropsychological tests. Brain Phe and Tyr in parietal white matter (PWM) were compared to results in gray matter of the posterior cingulate gyrus (PCG). RESULTS: Brain Phe ranged from 101 to 182 (mean = 136.76 +/- 23.77) MUmol/L in PCG and 76 to 185 (mean = 130.11 +/- 37.88) MUmol/L in PWM. Brain Tyr ranged from 4.0 to 7.4 (mean = 5.44 +/- 1.01) MUmol/L in PCG and 4.1 to 8.4 (mean = 5.90 +/- 1.48) MUmol/L in PWM. Correlation coefficients were largest for brain Phe PWM and measures of auditory memory (rho = -0.79), anxiety (rho = 0.79), and executive functioning (rho = 0.69). Associations were in the expected direction, with higher brain Phe and lower brain Tyr related to poorer functioning. The two participants with severe structural MRI abnormalities had low brain Tyr levels in PCG and 3/5 of the participants with moderate to severe MRI abnormalities had higher than average brain Phe levels. CONCLUSION: COSY has the potential to quantify brain Phe and Tyr at low concentrations and in specific brain regions. In this pilot study, these biomarkers were associated with indices of neuropsychological functioning. Additional studies are needed to validate the COSY results. PMID- 27677922 TI - Assessing the Potential Effects of Active Site Mg2+ Ions in the glmS Ribozyme Cofactor Complex. AB - Ribozymes employ diverse catalytic strategies in their self-cleavage mechanisms, including the use of divalent metal ions. This work explores the effects of Mg2+ ions in the active site of the glmS ribozyme-GlcN6P cofactor complex using computational methods. Deleterious and potentially beneficial effects of an active site Mg2+ ion on the self-cleavage reaction were identified. The presence of a Mg2+ ion near the scissile phosphate oxygen atoms at the cleavage site was determined to be deleterious, and thereby anticatalytic, due to electrostatic repulsion of the cofactor, disruption of key hydrogen-bonding interactions, and obstruction of nucleophilic attack. On the other hand, the presence of a Mg2+ ion at another position in the active site, the Hoogsteen face of the putative base, was found to avoid these deleterious effects and to be potentially catalytically favorable owing to the stabilization of negative charge and pKa shifting of the guanine base. PMID- 27677923 TI - Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa. AB - INTRODUCTION: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy in the world, with the majority of cases in sub-Saharan Africa. Concomitant nutritional deficiencies, infections or exposure to environmental toxins exacerbate chronic anemia in children with SCD. The resulting relative anemia is associated with increased risk of strokes, poor cognitive function and impaired growth. It may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa. This review will focus on the epidemiology, clinical sequelae, and treatment of relative anemia in children with SCD living in low and middle-income countries in sub-Saharan Africa. Areas covered: The causes and treatment of relative anemia in children with SCD in sub-Saharan Africa. The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles regarding relative anemia in children with SCD in sub-Saharan Africa. Expert commentary: Anemia due to nutritional deficiencies and infectious diseases such as helminthiasis and malaria are prevalent in sub-Saharan Africa. Their co-existence in children with SCD increases morbidity and mortality. Therefore, preventing, diagnosing and treating the underlying cause of this relative anemia will improve SCD-related outcomes in children in sub-Saharan Africa. PMID- 27677921 TI - Rhinovirus C is associated with wheezing and rhinovirus A is associated with pneumonia in hospitalized children in Morocco. AB - Human rhinovirus (RV) is commonly associated with severe acute lower respiratory infections (ALRI) in children. We aimed to describe the distribution of RV species and associations between RV species and clinical features in children hospitalized with clinically severe pneumonia (CSP) in Morocco. Nasopharyngeal aspirates (NPAs) were collected from 700 children, 2-59 months of age, admitted with CSP to the Hopital d'Enfants de Rabat in Morocco. At least one respiratory virus was identified in 92% of children, of which RV was the most common (53%). PCR assays, sequencing, and phylogenetic tree analyses were carried out on 183 RV positive NPAs to determine RV species and genotypes. Of 157 successfully genotyped NPAs, 60 (38.2%) were RV-A, 8 (5.1%) were RV-B, and 89 (56.7%) were RV C. Wheezing and cyanosis were more common in RV-C-positive than RV-A-positive children (80.9% vs. 56.7%; P = 0.001 for wheezing and 10.1% vs. 0%; P = 0.011 for cyanosis). Physician's discharge diagnosis of pneumonia was more frequent among RV-A-positive (40.0%) than RV-C-positive children (20.2%; P = 0.009). RV-A and RV C showed distinct seasonal patterns. Our findings suggest that RV-C is associated with wheezing illness while RV-A is associated with pneumonia. J. Med. Virol. 89:582-588, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27677925 TI - Ethical issues and best practice in clinically based genomic research: Exeter Stakeholders Meeting Report. AB - Current guidelines on consenting individuals to participate in genomic research are diverse. This creates problems for participants and also for researchers, particularly for clinicians who provide both clinical care and research to their patients. A group of 14 stakeholders met on 7 October 2015 in Exeter to discuss the ethical issues and the best practice arising in clinically based genomic research, with particular emphasis on the issue of returning results to study participants/patients in light of research findings affecting research and clinical practices. The group was deliberately multidisciplinary to ensure that a diversity of views was represented. This report outlines the main ethical issues, areas of best practice and principles underlying ethical clinically based genomic research discussed during the meeting. The main point emerging from the discussion is that ethical principles, rather than being formulaic, should guide researchers/clinicians to identify who the main stakeholders are to consult with for a specific project and to incorporate their voices/views strategically throughout the lifecycle of each project. We believe that the mix of principles and practical guidelines outlined in this report can contribute to current debates on how to conduct ethical clinically based genomic research. PMID- 27677924 TI - Selective activation of vascular Kv 7.4/Kv 7.5 K+ channels by fasudil contributes to its vasorelaxant effect. AB - BACKGROUND AND PURPOSE: Kv 7 (Kv 7.1-7.5) channels play an important role in the regulation of neuronal excitability and the cardiac action potential. Growing evidence suggests Kv 7.4/Kv 7.5 channels play a crucial role in regulating vascular smooth muscle contractility. Most of the reported Kv 7 openers have shown poor selectivity across these five subtypes. In this study, fasudil - a drug used for cerebral vasospasm - has been found to be a selective opener of Kv 7.4/Kv 7.5 channels. EXPERIMENTAL APPROACH: A perforated whole-cell patch technique was used to record the currents and membrane potential. Homology modelling and a docking technique were used to investigate the interaction between fasudil and the Kv 7.4 channel. An isometric tension recording technique was used to assess the vascular tension. KEY RESULTS: Fasudil selectively and potently enhanced Kv 7.4 and Kv 7.4/Kv 7.5 currents expressed in HEK293 cells, and shifted the voltage-dependent activation curve in a more negative direction. Fasudil did not affect either Kv 7.2 and Kv 7.2/Kv 7.3 currents expressed in HEK293 cells, the native neuronal M-type K+ currents, or the resting membrane potential in small rat dorsal root ganglia neurons. The Val248 in S5 and Ile308 in S6 segment of Kv 7.4 were critical for this activating effect of fasudil. Fasudil relaxed precontracted rat small arteries in a concentration-dependent fashion; this effect was antagonized by the Kv 7 channel blocker XE991. CONCLUSIONS AND IMPLICATIONS: These results suggest that fasudil is a selective Kv 7.4/Kv 7.5 channel opener and provide a new dimension for developing selective Kv 7 modulators and a new prospective for the use, action and mechanism of fasudil. PMID- 27677926 TI - Mnemonic anosognosia in Alzheimer's disease is caused by a failure to transfer online evaluations of performance: Evidence from memory training programs. AB - INTRODUCTION: There is a debate about the ability of patients with Alzheimer's disease to build an up-to-date representation of their memory function, which has been termed mnemonic anosognosia. This form of anosognosia is typified by accurate online evaluations of performance, but dysfunctional or outmoded representations of function more generally. METHOD: We tested whether people with Alzheimer's disease could adapt or change their representations of memory performance across three different six-week memory training programs using global judgements of learning. RESULTS: We showed that whereas online assessments of performance were accurate, patients continued to make inaccurate overestimations of their memory performance. This was despite the fact that the magnitude of predictions shifted according to the memory training. That is, on some level patients showed an ability to change and retain a representation of performance over time, but it was a dysfunctional one. For the first time in the literature we were able to use an analysis using correlations to support this claim, based on a large heterogeneous sample of 51 patients with Alzheimer's disease. CONCLUSION: The results point not to a failure to retain online metamemory information, but rather that this information is never used or incorporated into longer term representations, supporting but refining the mnemonic anosognosia hypothesis. PMID- 27677927 TI - Standardizing Direct Observation for Assessing Compliance to a Daily Chlorhexidine Bathing Protocol Among Hospitalized Patients. PMID- 27677928 TI - Birthweight in pregnant women with protein S deficiency treated with low molecular-weight heparin: a retrospective cohort study. AB - OBJECTIVE: To determine the risk of small-for-gestational-age (SGA) and intrauterine growth retardation (IUGR) in pregnant women with protein S (PS) deficiency who received low-molecular-weight heparin (LMWH). METHODS: Retrospective cohort study of pregnant women seen from January 2002 to December 2011. The study cohort comprised a total of 328 patients with PS deficiency, who received prophylactic enoxaparin during pregnancy. The control cohort included 11 884 pregnant women without significant past medical history. The risk of SGA and IUGR was calculated as odds ratio. Multivariate regression analysis over the entire reference population was performed determining the risk of both SGA and IUGR by adjusting for maternal age, first delivery, maternal underweight status, pre-eclampsia, other treated thrombophilias or history of recurrent abortion. RESULTS: The SGA rates in the PS deficiency and control cohorts were 10.7% and 8.5%, respectively (p > 0.05). There was no increased risk of SGA (unadjusted OR = 1.28, 95% confidence interval [CI] 0.9-1.83; adjusted OR = 1.35, 95% CI 0.91 2.01). The IUGR rate was 2.7% in pregnant women with PS deficiency versus 4.1% in the control group (p > 0.05). Also, we did not find a significant risk of IUGR (OR = 0.66; 95% CI 0.34-1.28; adjusted OR = 0.843; 95% CI 0.42-1.70). CONCLUSIONS: In women with PS deficiency treated with LMWH, the risk of SGA and IUGR is similar to the one found in healthy pregnant women. PMID- 27677929 TI - Polyamines and transglutaminases: future perspectives. PMID- 27677930 TI - Intrinsic GTPase activity of a ribosomal maturation protein CgtA is associated with its inter-domain movement: insights from MD simulations and biochemical studies. AB - CgtA is an essential ribosome associated GTPase protein of bacteria. It has three domains, viz., Obg, GTPase, and C-terminal domain. It is a multifunctional protein and it is being considered as a potential drug target against bacterial infections. Despite the importance, CgtA's action mechanisms are not well known which warrants further study. Towards that goal, we are pursuing biochemical and computational studies in Vibrio cholerae CgtA (CgtAvc). Biochemically we found that a single amino acid substitution from Gly98 to Asp98 belonging to the Obg domain caused reduced GTPase activity of CgtAvc. The results from our comparative MD simulations studies revealed that in silico amino acid substitution for Gly98Asp influenced the inter-domain movement between Obg domain and GTPase domain. Moreover, we found significant alteration of intra-domain movements among the P-loop, G4 box, and G5 box of the GTPase domain, implying a potential cause for the reduced GTPase activity. PMID- 27677931 TI - How would I live with a disability? Expectations of bio-psychosocial consequences and assistive technology use. AB - PURPOSE: It is widely accepted that social dimensions are crucial when facing a disability. More specifically, a normative incentive to conceal one's disability, which can lead to abandonment of assistive technology devices (ATD), is often reported. This study seeks to examine this norm. METHOD: The expected consequences of having a disability were measured using a sample of 549 able bodied students from three groups. RESULTS: The results showed that the expected consequences of having a disability and therefore the descriptive norms associated with disability were less negative for the participants who were familiar with disability, but higher for sports students. Furthermore, the relation between objective and subjective consequences (having a disability and feeling disabled, respectively) and public and private use of ATD were modelled. The model shows that both higher objective and lower subjective consequences were linked to higher ATD use in public and, indirectly, in private. CONCLUSION: The present study contributes to the literature on the normative elements related to the use of ATD. Indeed, it shows that when a person makes his/her disability a part of him/herself, she/he is expected to hide it and therefore to avoid using ATD. However, this assessment proves to be context-dependent and calls for the implementation of handicap awareness programs. Implications for Rehabilitation If faced with a disability, expecting to feel disabled and expecting lower objective consequences are linked to lower ATD use. Expected ATD use in private seems to be related to ATD use in public but not to the expected consequences of the disability. Expectations and therefore social norms about having a disability are highly context-dependent which encourages the implementation of handicap awareness programs. PMID- 27677932 TI - Investigational alpha-synuclein aggregation inhibitors: hope for Parkinson's disease. AB - INTRODUCTION: The therapeutic management of Parkinson's disease (PD) is challenging and has not been fully resolved. The main challenges include motor fluctuations and levodopa-induced dyskinesia. Moreover, no disease-modifying or neuroprotective therapy is currently available. Areas covered: This review focuses on alpha-synuclein aggregation inhibitors and their therapeutic role in PD, with special attention to heat shock proteins, immunotherapy (active and passive), the potential of targeting the Ser129 phosphorylation site, and the antibiotic possibilities. Expert opinion: The induction of chaperones may provide beneficial strategy to target synucleinopathies, but further investigations are needed to find the best options. The promising preclinical results with immunotherapy suggest that it may be a valuable disease-modifying therapy in PD in the future. Clinical trials are currently in the initial phases, and future studies need to confirm the beneficial therapeutic effect in humans and clarify open questions as regards the exact mode of action and potential safety concerns. In case of covalent modifications, phosphorylation of alpha-synuclein is of outstanding importance; however, conflicting results and open questions exist which necessitate clarification. In vitro results suggest that several antibiotics may also influence alpha-synuclein aggregation, but these results are to be confirmed in the future. PMID- 27677933 TI - Proteasome dynamics between proliferation and quiescence stages of Saccharomyces cerevisiae. AB - The ubiquitin-proteasome system (UPS) plays a critical role in cellular protein homeostasis and is required for the turnover of short-lived and unwanted proteins, which are targeted by poly-ubiquitination for degradation. Proteasome is the key protease of UPS and consists of multiple subunits, which are organized into a catalytic core particle (CP) and a regulatory particle (RP). In Saccharomyces cerevisiae, proteasome holo-enzymes are engaged in degrading poly ubiquitinated substrates and are mostly localized in the nucleus during cell proliferation. While in quiescence, the RP and CP are sequestered into motile and reversible storage granules in the cytoplasm, called proteasome storage granules (PSGs). The reversible nature of PSGs allows the proteasomes to be transported back into the nucleus upon exit from quiescence. Nuclear import of RP and CP through nuclear pores occurs via the canonical pathway that includes the importin alphabeta heterodimer and takes advantage of the Ran-GTP gradient across the nuclear membrane. Dependent on the growth stage, either inactive precursor complexes or mature holo-enzymes are imported into the nucleus. The present review discusses the dynamics of proteasomes including their assembly, nucleo cytoplasmic transport during proliferation and the sequestration of proteasomes into PSGs during quiescence. [Formula: see text]. PMID- 27677934 TI - Adolescent methylmercury exposure affects choice and delay discounting in mice. AB - The developing fetus is vulnerable to low-level exposure to methylmercury (MeHg), an environmental neurotoxicant, but the consequences of exposure during the adolescent period remain virtually unknown. The current experiments were designed to assess the effects of low-level MeHg exposure during adolescence on delay discounting, preference for small, immediate reinforcers over large, delayed ones, using a mouse model. Thirty-six male C57BL/6n mice were exposed to 0, 0.3, or 3.0ppm mercury (as MeHg) via drinking water from postnatal day 21 through 59, encompassing the murine adolescent period. As adults, mice lever pressed for a 0.01-cc droplet of milk solution delivered immediately or four 0.01-cc droplets delivered after a delay. Delays ranged from 1.26 to 70.79s, and all were presented within a session. A model based on the Generalized Matching Law indicated that sensitivity to reinforcer magnitude was lower for MeHg-exposed mice relative to controls, indicating that responding in MeHg-exposed mice was relatively indifferent to the larger reinforcer. Sensitivity to reinforcer delay was reduced (delay discounting was decreased) in the 0.3-ppm group, but not in the 3.0-ppm group, compared to controls. Adolescence is a developmental period during which the brain and behavior may be vulnerable to MeHg exposure. As with gestational MeHg exposure, the effects are reflected in the impact of reinforcing stimuli. PMID- 27677936 TI - A method for whole protein isolation from human cranial bone. AB - The presence of the dense hydroxyapatite matrix within human bone limits the applicability of conventional protocols for protein extraction. This has hindered the complete and accurate characterization of the human bone proteome thus far, leaving many bone-related disorders poorly understood. We sought to refine an existing method of protein extraction from mouse bone to extract whole proteins of varying molecular weights from human cranial bone. Whole protein was extracted from human cranial suture by mechanically processing samples using a method that limits protein degradation by minimizing heat introduction to proteins. The presence of whole protein was confirmed by western blotting. Mass spectrometry was used to sequence peptides and identify isolated proteins. The data have been deposited to the ProteomeXchange with identifier PXD003215. Extracted proteins were characterized as both intra- and extracellular and had molecular weights ranging from 9.4 to 629 kDa. High correlation scores among suture protein spectral counts support the reproducibility of the method. Ontology analytics revealed proteins of myriad functions including mediators of metabolic processes and cell organelles. These results demonstrate a reproducible method for isolation of whole protein from human cranial bone, representing a large range of molecular weights, origins and functions. PMID- 27677937 TI - Novel treatment options for Bouveret's syndrome: a comprehensive review of 61 cases of successful endoscopic treatment. AB - INTRODUCTION: In Bouveret's syndrome, a biliary stone obstructs the duodenum. Surgical treatment is plagued by high morbidity and mortality. Therefore, endoscopic treatment has become a first-line approach. Areas covered: A literature search of Medline and Google Scholar databases was performed using the terms endoscopic treatment, non-operative treatment, Bouveret's syndrome, and gallstone ileus. Sixty-one cases of successful endoscopic treatment were found over the period 1978-2016 and are summarized herein. Therapeutic modalities used in 52 patients with complete success included mechanical lithotripsy (40% of cases), electrohydraulic lithotripsy (21% of cases), extraction of the intact stone and laser lithotripsy (15% of cases each), extracorporeal shockwave lithotripsy and duodenal stenting (4% of cases each). In the remaining 9 patients, stone fragments migrated distally and required surgical removal. Cholecystectomy was performed in five (8.2%) of 61 patients and gallbladder cancer was detected in three (4.9%) patients. Expert commentary: Meticulous preparation, including that of instruments, personnel, patient anesthesia, and X ray availability, is key to success in this unusual situation. Partial success (stone fragmentation and mobilization to another location) may render surgery easier as these patients present with dense adherences in the right upper quadrant. Cholecystectomy is reserved for highly selected patients (e.g. relapsing ileus, gallbladder cancer). PMID- 27677938 TI - Initiating and imaging the coherent surface dynamics of charge carriers in real space. AB - The tip of a scanning tunnelling microscope is an atomic-scale source of electrons and holes. As the injected charge spreads out, it can induce adsorbed molecules to react. By comparing large-scale 'before' and 'after' images of an adsorbate covered surface, the spatial extent of the nonlocal manipulation is revealed. Here, we measure the nonlocal manipulation of toluene molecules on the Si(111)-7 * 7 surface at room temperature. Both the range and probability of nonlocal manipulation have a voltage dependence. A region within 5-15 nm of the injection site shows a marked reduction in manipulation. We propose that this region marks the extent of the initial coherent (that is, ballistic) time dependent evolution of the injected charge carrier. Using scanning tunnelling spectroscopy, we develop a model of this time-dependent expansion of the initially localized hole wavepacket within a particular surface state and deduce a quantum coherence (ballistic) lifetime of ~10 fs. PMID- 27677939 TI - The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes. AB - A failing heart shows severe energy insufficiency, and it is presumed that this energy shortage plays a critical role in the development of cardiac dysfunction. However, little is known about the mechanisms that cause energy metabolic alterations in the failing heart. Here, we show that the novel RING-finger protein 207 (RNF207), which is specifically expressed in the heart, plays a role in cardiac energy metabolism. Depletion of RNF207 in neonatal rat cardiomyocytes (NRCs) leads to a reduced cellular concentration of adenosine triphosphate (ATP) and mitochondrial dysfunction. Consistent with this result, we observed here that the expression of RNF207 was significantly reduced in mice with common cardiac diseases including heart failure. Intriguingly, proteomic approaches revealed that RNF207 interacts with the voltage-dependent anion channel (VDAC), which is considered to be a key regulator of mitochondria function, as an RNF207 interacting protein. Our findings indicate that RNF207 is involved in ATP production by cardiomyocytes, suggesting that RNF207 plays an important role in the development of heart failure. PMID- 27677935 TI - Potential roles of cholinergic modulation in the neural coding of location and movement speed. AB - Behavioral data suggest that cholinergic modulation may play a role in certain aspects of spatial memory, and neurophysiological data demonstrate neurons that fire in response to spatial dimensions, including grid cells and place cells that respond on the basis of location and running speed. These neurons show firing responses that depend upon the visual configuration of the environment, due to coding in visually-responsive regions of the neocortex. This review focuses on the physiological effects of acetylcholine that may influence the sensory coding of spatial dimensions relevant to behavior. In particular, the local circuit effects of acetylcholine within the cortex regulate the influence of sensory input relative to internal memory representations via presynaptic inhibition of excitatory and inhibitory synaptic transmission, and the modulation of intrinsic currents in cortical excitatory and inhibitory neurons. In addition, circuit effects of acetylcholine regulate the dynamics of cortical circuits including oscillations at theta and gamma frequencies. These effects of acetylcholine on local circuits and network dynamics could underlie the role of acetylcholine in coding of spatial information for the performance of spatial memory tasks. PMID- 27677942 TI - Morphological variability, ultrastructure and molecular characterisation of Hysterothylacium reliquens (Norris & Overstreet, 1975) (Nematoda: Raphidascarididae) from the oriental sole Brachirus orientalis (Bloch & Schneider) (Pleuronectiformes: Soleidae). AB - Hysterothylacium reliquens (Norris & Overstreet, 1975), a common ascaridoid nematode parasitic in the marine fishes in the Indian and Atlantic Oceans, has been reported to exhibit remarkable morphological variability in the lengths of body, oesophagus and spicules, and the number and arrangement of postcloacal papillae. In order to determine whether H. reliquens with a broad range of morphological variability in the above-mentioned respects, represents a complex of sibling species or a single species, and to evaluate if the specimens of H. reliquens collected from the Indian and Atlantic Oceans are the same species, numbers of H. reliquens collected from the oriental sole Brachirus orientalis (Bloch & Schneider) (Pleuronectiformes: Soleidae) in the Arabian Gulf (off Iraq) were characterised using molecular approaches by sequencing and analysing the ribosomal [large ribosomal DNA (28S) and internal transcribed spacer (ITS)] and mitochondrial [cytochrome c oxidase subunit 2 (cox2)] target regions, respectively. The results of molecular analysis strongly supported that: (i) the broad ranges of morphological variability in the above-mentioned respects in the newly collected specimens of H. reliquens, should be considered as intraspecific variation and the nematode material collected from B. orientalis in the Arabian Gulf represented a single species; (ii) the specimens of H. reliquens collected from the Indian and Atlantic Oceans belong to the same species, but they possibly represent different geographical populations. Moreover, the detailed morphology of the labial papillae, lateral alae, excretory pore, distal end of spicules, midventral precloacal papilla, phasmids and caudal papillae was revealed by SEM for the first time. The molecular and morphological data of H. reliquens obtained herein contribute to a more accurate diagnosis of this little known ascaridoid nematode. PMID- 27677940 TI - Poverty, partner discord, and divergent accounts; a mixed methods account of births before arrival to health facilities in Morogoro Region, Tanzania. AB - BACKGROUND: Births before arrival (BBA) to health care facilities are associated with higher rates of perinatal morbidity and mortality compared to facility deliveries or planned home births. Research on such births has been conducted in several high-income countries, but there are almost no studies from low-income settings where a majority of maternal and newborn deaths occur. METHODS: Drawing on a household survey of women and in-depth interviews with women and their partners, we examined the experience of BBA in rural districts of Morogoro Region, Tanzania. RESULTS: Among survey respondents, 59 births (4 %) were classified as BBAs. Most of these births occurred in the presence of a family member (47 %) or traditional birth attendant (24 %). Low socioeconomic status was the strongest predictor of BBA. After controlling for wealth via matching, high parity and a low number of antenatal care (ANC) visits retained statistical significance. While these variables are useful indicators of which women are at greater risk of BBA, their predictive power is limited in a context where many women are poor, multiparous, and make multiple ANC visits. In qualitative interviews, stories of BBAs included themes of partner disagreement regarding when to depart for facilities and financial or logistical constraints that underpinned departure delays. Women described wanting to depart earlier to facilities than partners. CONCLUSION: As efforts continue to promote facility birth, we highlight the financial demands associated with facility delivery and the potential for these demands to place women at a heightened risk for BBAs. PMID- 27677943 TI - High reward expectancy during methylphenidate depresses the dopaminergic response to gain and loss. AB - Dopamine plays an important role in goal-directed behavior, through its modulatory influence on striatal neurons. It is unclear whether tonic dopamine levels, which regulate the vigor of acting, interact with the phasic dopamine response to reward that drives instrumental behavior. In a randomized placebo controlled study in healthy volunteers, we show that methylphenidate, a drug that increases tonic dopamine levels, systematically reduced striatal phasic BOLD responses to gain and loss in a gambling task as measured with fMRI. It also increased response vigor and reward expectancy-related BOLD signals in the ventral striatum. These findings suggest that striatal tonic dopamine levels constitute an average reward expectation signal that modulates the phasic dopaminergic response to reward. This offers opportunities for treatment of behavioral disorders associated with abnormal reward sensitivity. PMID- 27677944 TI - Reward processing in the value-driven attention network: reward signals tracking cue identity and location. AB - Through associative reward learning, arbitrary cues acquire the ability to automatically capture visual attention. Previous studies have examined the neural correlates of value-driven attentional orienting, revealing elevated activity within a network of brain regions encompassing the visual corticostriatal loop [caudate tail, lateral occipital complex (LOC) and early visual cortex] and intraparietal sulcus (IPS). Such attentional priority signals raise a broader question concerning how visual signals are combined with reward signals during learning to create a representation that is sensitive to the confluence of the two. This study examines reward signals during the cued reward training phase commonly used to generate value-driven attentional biases. High, compared with low, reward feedback preferentially activated the value-driven attention network, in addition to regions typically implicated in reward processing. Further examination of these reward signals within the visual system revealed information about the identity of the preceding cue in the caudate tail and LOC, and information about the location of the preceding cue in IPS, while early visual cortex represented both location and identity. The results reveal teaching signals within the value-driven attention network during associative reward learning, and further suggest functional specialization within different regions of this network during the acquisition of an integrated representation of stimulus value. PMID- 27677945 TI - RNA-seq analysis of the hypothalamic transcriptome reveals the networks regulating physiopathological progress in the diabetic GK rat. AB - The Goto-Kakizaki (GK) rat is an animal model of non-obese type 2 diabetes (T2D). The GK rat was generated through the introduction of various genetic mutations from continuous inbreeding; these rats develop diabetes spontaneously. The mutated genes in GK rats may play key roles in the regulation of diabetes. The hypothalamus plays a central role in systematic energy homeostasis. Here, the hypothalamic transcriptomes in GK and Wistar rats at 4, 8 and 12 weeks were investigated by RNA-seq, and multiple variants and gene expression profiles were obtained. The number of variants identified from GK rats was significantly greater than that of Wistar rats, indicating that many variants were fixed and heritable in GK rats after selective inbreeding. The differential gene expression analysis indicated that GK rats had a dysfunctional hypothalamic melanocortin system and attenuation of the hypothalamic glucose-sensing pathway. In addition, we generated integrated gene network modules by combining the protein-protein interaction (PPI) network, co-expression network and mutations in GK and Wistar rats. In the modules, GK-specific genes, such as Bad, Map2k2, Adcy3, Adcy2 and Gstm6, may play key roles in hypothalamic regulation in GK rats. Our research provides a comprehensive map of the abnormalities in the GK rat hypothalamus, which reveals the new mechanisms of pathogenesis of T2D. PMID- 27677947 TI - The effect of rod orientation on electrical anisotropy in silver nanowire networks for ultra-transparent electrodes. AB - Two-dimensional networks made of metal nanowires are excellent paradigms for the experimental observation of electrical percolation caused by continuous jackstraw like physical pathways. Such systems became very interesting as alternative material in transparent electrodes, which are fundamental components in display devices. This work presents the experimental characterization of low-haze and ultra-transparent electrodes based on silver nanowires. The films are created by dip-coating, a feasible and scalable liquid film coating technique. We have found dominant alignment of the silver nanowires in withdrawal direction. The impact of this structural anisotropy on electrical anisotropy becomes more pronounced for low area coverage. The rod alignment does not influence the technical usability of the films as significant electrical anisotropy occurs only at optical transmission higher than 99 %. For films with lower transmission, electrical anisotropy becomes negligible. In addition to the experimental work, we have carried out computational studies in order to explain our findings further and compare them to our experiments and previous literature. This paper presents the first experimental observation of electrical anisotropy in two-dimensional silver nanowire networks close at the percolation threshold. PMID- 27677948 TI - Demographic and reproductive plasticity across the depth distribution of a coral reef fish. AB - As humans expand into natural environments, populations of wild organisms may become relegated to marginal habitats at the boundaries of their distributions. In the ocean, mesophotic coral ecosystems (30-150 m) at the depth limit of photosynthetic reefs are hypothesized to act as refuges that are buffered from anthropogenic and natural disturbances, yet the viability and persistence of subpopulations in these peripheral habitats remains poorly understood. To assess the potential for mesophotic reefs to support robust coral reef fish populations, we compared population density and structure, growth, size, and reproductive output of the bicolor damselfish (Stegastes partitus) from shallow (<10 m), deep shelf (20-30 m), and mesophotic reefs (60-70 m) across the Florida Platform. Population densities decreased and size and age distributions shifted toward older and larger individuals in deeper habitats. Otolith-derived ages indicated that S. partitus found on mesophotic reefs reach larger asymptotic sizes and have longer lifespans than fish in shallower habitats. Based on measurements of oocyte area and batch fecundity, mesophotic fish also have higher reproductive investment. These demographic patterns indicate that mesophotic fish populations composed of large, fecund individuals produce high condition larvae and rely on longevity of individuals for population persistence and viability. PMID- 27677950 TI - Resource Loss Moderates the Association Between Child Abuse and Current PTSD Symptoms Among Women in Primary-Care Settings. AB - This study examined if abuse during childhood, rape in adulthood, and loss of resources predict a woman's probability of reporting symptoms of posttraumatic stress disorder (PTSD), and whether resource loss moderates the association between reporting childhood abuse and PTSD symptoms. The sample included 767 women and was collected in publicly funded primary-care settings. Women who reported having been abused during childhood also reported more resource loss, more acute PTSD symptoms, and having suffered more adult rape than those who reported no childhood abuse. Hierarchical logistic regression yielded a two variable additive model in which child abuse and adult rape predict the probability of reporting or not any PTSD symptoms, explaining 59.7% of the variance. Women abused as children were 1 to 2 times more likely to report PTSD symptoms, with sexual abuse during childhood contributing most strongly to this result. Similarly, women reporting adult rape were almost twice as likely to report symptoms of PTSD as those not reporting it. Resource loss was unexpectedly not among the predictors but a moderation analysis showed that such loss moderated the association between child abuse and current PTSD symptoms, with resource loss increasing the number and severity of PTSD symptoms in women who also reported childhood abuse. The findings highlight the importance of early assessment and intervention in providing mental health care to abused, neglected, and impoverished women to help them prevent and reverse resource loss and revictimization. PMID- 27677949 TI - Structural determinants for NF-Y/DNA interaction at the CCAAT box. AB - The recently determined crystal structures of the sequence-specific transcription factor NF-Y have illuminated the structural mechanism underlying transcription at the CCAAT box. NF-Y is a trimeric protein complex composed by the NF-YA, NF-YB, and NF-YC subunits. NF-YB and NF-YC contain a histone-like domain and assemble on a head-to-tail fashion to form a dimer, which provides the structural scaffold for the DNA sugar-phosphate backbone binding (mimicking the nucleosome H2A/H2B DNA assembly) and for the interaction with NF-YA. The NF-YA subunit hosts two structurally extended alpha-helices; one is involved in NF-YB/NF-YC binding and the other inserts deeply into the DNA minor groove, providing exquisite sequence specificity for recognition and binding of the CCAAT box. The analysis of these structural data is expected to serve as a powerful guide for future experiments aimed at understanding the role of post-translational modification at NF-Y regulation sites and to unravel the three-dimensional architecture of higher order complexes formed between NF-Y and other transcription factors that act synergistically for transcription activation. Moreover, these structures represent an excellent starting point to challenge the formation of a stable hybrid nucleosome between NF-Y and core histone proteins, and to rationalize the fine molecular details associated with the wide combinatorial association of plant NF-Y subunits. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani. PMID- 27677951 TI - A Global Exploratory Analysis of Men Participating in Gender-Based Violence Prevention. AB - Organizations addressing gender-based violence (GBV) increasingly include men as partners in prevention efforts. However, little is known about men who get involved in those efforts and what specific actions they take. We present analyses of data from an international sample of men involved in gender-based prevention work that aimed to describe (a) the nature of participants' involvement in prevention efforts, in both formal programming and in their daily lives; (b) characteristics of engaged men, including gender and bystander-related attitudes and beliefs, and social networks; and (c) factors that sustain men's involvement in GBV movements over time. Comparisons across global regions for these variables were also conducted. A total of 379 male-identified participants above 18 who had attended a GBV event in the past year completed an online survey (available in English, French, and Spanish). Respondents represented all continents except Antarctica, although North America was over-represented in the sample. Overall, respondents scored well above North American norms for men on support for gender equality and recognition of male privilege, and this was true across all geographic regions. Men in all regions reported moderate support from friends and somewhat less support from male relatives for their involvement in GBV prevention. Respondents in all regions reported high levels of active bystander and violence-preventive behavior. The most commonly reported motivations for involvement in GBV prevention included concern for related social justice issues, exposure to the issue of violence through work, hearing a moving story, or disclosures about domestic or sexual violence. Results were mainly similar across regions, but when regional differences emerge, they tended to be contrasts between the global north and global south, highlighting the importance of cross-fertilization across regions and a willingness to adapt critical learnings in new geographic settings. PMID- 27677952 TI - A new design for a green calcium indicator with a smaller size and a reduced number of calcium-binding sites. AB - Genetically encoded calcium indicators (GECIs) are mainly represented by two- or one-fluorophore-based sensors. One type of two-fluorophore-based sensor, carrying Opsanus troponin C (TnC) as the Ca2+-binding moiety, has two binding sites for calcium ions, providing a linear response to calcium ions. One-fluorophore-based sensors have four Ca2+-binding sites but are better suited for in vivo experiments. Herein, we describe a novel design for a one-fluorophore-based GECI with two Ca2+-binding sites. The engineered sensor, called NTnC, uses TnC as the Ca2+-binding moiety, inserted in the mNeonGreen fluorescent protein. Monomeric NTnC has higher brightness and pH-stability in vitro compared with the standard GECI GCaMP6s. In addition, NTnC shows an inverted fluorescence response to Ca2+. Using NTnC, we have visualized Ca2+ dynamics during spontaneous activity of neuronal cultures as confirmed by control NTnC and its mutant, in which the affinity to Ca2+ is eliminated. Using whole-cell patch clamp, we have demonstrated that NTnC dynamics in neurons are similar to those of GCaMP6s and allow robust detection of single action potentials. Finally, we have used NTnC to visualize Ca2+ neuronal activity in vivo in the V1 cortical area in awake and freely moving mice using two-photon microscopy or an nVista miniaturized microscope. PMID- 27677953 TI - Epstein-Barr Virus-associated Gastric Cancer and Potential Mechanisms of Oncogenesis. AB - INTRODUCTION: EBV-associated Gastric Cancer (EBVaGC) comprises about 9% of all cases of GC and constitutes a distinct clinicopathological and molecular entity. The pattern of viral expression in EBVaGC cannot be set to any of the previously EBV-associated malignancies. Several lines of evidence support that viral expression in EBVaGC is characterized by high transcription of the BamH1- A rightward transcript (BART), low-levels of EBNA-1 and lack of LMP1. The high transcription activity of the BamH1-A region is importantly directed to express BART miRNAs, supporting a critical role for these miRNAs during epithelial cell infection and carcinogenesis. Several studies have shown that promoter hypermethylation is also a prominent feature of EBVaGC. Based on the recent TCGA report, the specific fingerprint of genomic alterations in EBVaGC is marked by mutations in PIK3CA, ARID1A and BCOR genes, and amplification of 9p24.1 that harbors the genes for the JAK2, PD-L1 and PD-L2 proteins. The specific programs of viral gene expression, promoter methylation and genomic mutations found in EBVaGC target cell signaling pathways leading to increased proliferation, increased cell survival, immune evasion, augmented EMT and acquisition of stemness features. Less understood is the participation of EBV in chronic gastric inflammation, but some studies argue that EBV, similar to and together with Helicobacter pylori, is an early participant in the GC oncogenic process through promoting chronic inflammation and increased tissue damage. CONCLUSION: Here, we discuss the principal and distinctive carcinogenic routes promoted by EBV in the gastric epithelium. PMID- 27677954 TI - Hepatitis B Virus (HBV) Infection and Hepatocellular Carcinoma- New Insights for an Old Topic. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the most deadly form of liver cancer. Chronic hepatitis and subsequent liver fibrosis and cirrhosis are the major causes of HCC. HBV infection results not only in HCC but also extra-hepatic cancers. However, the importance and approaches for HCC screening in HBV infected individuals, the risk factors of HCC, the possible mechanisms leading to HCC and the potential therapeutic approaches of HBV-related HCC have less been systematic reviewed. METHODS: In this study, we reviewed the screening, risk, new biomarker, mechanism and therapeutic of HBV-related HCC. RESULTS: Serum AFP should be used for the HCC screening in CHB patients. Higher HBV viral load is associated with increased risk of HCC. HBV genotype and genetic polymorphism contribute to the risk of HCC.Ku86, Ku86 antibody, miR-18a, miR-122 and miR-150 may be reliable markers of HBVrelated HCC. MicroRNAs and HBx play a key role in HBV-related HCC. Two types of drugs, conventional interferon (IFN), and nucleoside analogs (NAs), have recently become available for the treatment of CHB infection. However, treatment guidelines for these patients have not yet established. CONCLUSION: A comprehensive understanding of how HBV infection causes HCC is of great importance in developing more effective antiviral therapy and prevention of late stage consequences such as cirrhosis and HCC. Regular screening in HBV infected individuals is a practically useful approach in reducing the HCC incidence in these patients. More reliable markers for HCC early detection should be explored. Combining IFNs and NAs with other curative approaches have superior benefits in preventing HCC recurrence. PMID- 27677946 TI - Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. AB - Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly supports that elevated lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve stenosis. The Mendelian randomization approach used to infer causality is generally not affected by confounding and reverse causation, the major problems of observational epidemiology. This approach is particularly valuable to study causality of Lp(a), as single genetic variants exist that explain 27-28% of all variation in plasma Lp(a). The most important genetic variant likely is the kringle IV type 2 (KIV-2) copy number variant, as the apo(a) product of this variant influences fibrinolysis and thereby thrombosis, as opposed to the Lp(a) particle per se. We speculate that the physiological role of KIV-2 in Lp(a) could be through wound healing during childbirth, infections, and injury, a role that, in addition, could lead to more blood clots promoting stenosis of arteries and the aortic valve, and myocardial infarction. Randomized placebo-controlled trials of Lp(a) reduction in individuals with very high concentrations to reduce cardiovascular disease are awaited. Recent genetic evidence documents elevated Lp(a) as a cause of myocardial infarction, atherosclerotic stenosis, and aortic valve stenosis. PMID- 27677955 TI - Role of Oxidative Stress in Hepatitis C Virus Induced Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is the predominant cause of chronic liver diseases and HCC, particularly in Western countries. Multiple molecular mechanisms are involved in the development and progression of HCV-related HCC, of which oxidative stress plays a pivotal role. HCV infection induces overproduction of reactive oxygen species (ROS) and impairs the function of endogenous antioxidants. Excessive amount of ROS directly damages DNA, lipids and proteins. Meanwhile, ROS indirectly activates a series of signaling cascades, and modulates the activity of many transcription factors, resulting in altered expression of genes that control cell survival, proliferation, angiogenesis, invasion and metastasis. In this review, we aim to summarize the possible molecular mechanisms underlying the link between the oxidative stress and hepatocarcinogenesis in HCV infected individuals, in order to facilitate discovery of possible approaches or interventional targets for HCV-related HCC. PMID- 27677956 TI - Temporal patterns in the soundscape of the shallow waters of a Mediterranean marine protected area. AB - The study of marine soundscapes is an emerging field of research that contributes important information about biological compositions and environmental conditions. The seasonal and circadian soundscape trends of a marine protected area (MPA) in the Mediterranean Sea have been studied for one year using an autonomous acoustic recorder. Frequencies less than 1 kHz are dominated by noise generated by waves and are louder during the winter; conversely, higher frequencies (4-96 kHz) are dominated by snapping shrimp, which increase their acoustic activity at night during the summer. Fish choruses, below 2 kHz, characterize the soundscape at sunset during the summer. Because there are 13 vessel passages per hour on average, causing acoustic interference with fish choruses 46% of the time, this MPA cannot be considered to be protected from noise. On the basis of the high seasonal variability of the soundscape components, this study proposes a one-year acoustic monitoring protocol using the soundscape methodology approach and discusses the concept of MPA size. PMID- 27677957 TI - A lost tribe in the city: health status and needs of African asylum seekers and refugees in Hong Kong. AB - BACKGROUND: Hong Kong's resistance to be a signatory of the 1951 Geneva Convention and lack of domestic policies in this area has resulted in restrictions on access to healthcare amongst asylum seekers and refugees (ASRs). Using social determinants of health framework this study sought to identify health practices, problems and needs of African ASRs in Hong Kong. METHODS: A cross-sectional survey comprising of six domains including health status, health seeking behaviour and social experience targeted at adult African ASRs in Hong Kong was conducted through three local non-governmental organisations between February and April 2013. Outpatient care and inpatient care in the past 12 months were used as proxy measures of general and severe ill health respectively. Associations between the determinants of health factors with general or severe health was explored through logistic regressions. RESULTS: Majority of 374 participants were young, single, educated males having been in Hong Kong for over 5 years. A third of ARS (36.1 %) screened positive for depression. Most reported problems related to basic necessities (64.7-78.6 %) and access to health services (72.2 %). ASRs with relatively less education, health awareness or higher risk behaviours were less likely to have obtained outpatient or inpatient services. African ASRs reporting problems with case officers (aOR = 2.80; 95 % CI = 1.35 5.79) or illness in the past 30 days (aOR = 6.00; 95 % CI = 2.94-12.25) were more likely to report general ill health. Similarly, problems with the case officers (aOR = 3.76; 95 % CI = 1.97-7.18) and self-reported illness in the past 30 days (aOR = 3.32; 95 % CI= 1.68-6.57) were also significantly associated with severe ill health. At the health system level, those who reported experiencing difficulties accessing the medical services in Hong Kong are 3.29 (95 % CI = 1.48 7.31) and 4.12 (95 % CI = 1.73-9.79) times as likely to report general and severe ill health respectively. CONCLUSION: The host government should have moral and ethical obligations to attend to the health needs of ASRs. Evidently a number of structural and health system factors have significantly impacted the health of African ASRs in Hong Kong. Changes to current policies regarding how African ASRs are handled whilst in Hong Kong but, more immediately, improvements in healthcare access are needed. PMID- 27677958 TI - Rare variant association test in family-based sequencing studies. AB - The objective of this article is to introduce valid and robust methods for the analysis of rare variants for family-based exome chips, whole-exome sequencing or whole-genome sequencing data. Family-based designs provide unique opportunities to detect genetic variants that complement studies of unrelated individuals. Currently, limited methods and software tools have been developed to assist family-based association studies with rare variants, especially for analyzing binary traits. In this article, we address this gap by extending existing burden and kernel-based gene set association tests for population data to related samples, with a particular emphasis on binary phenotypes. The proposed approach blends the strengths of kernel machine methods and generalized estimating equations. Importantly, the efficient generalized kernel score test can be applied as a mega-analysis framework to combine studies with different designs. We illustrate the application of the proposed method using data from an exome sequencing study of autism. Methods discussed in this article are implemented in an R package 'gskat', which is available on CRAN and GitHub. PMID- 27677959 TI - A novel computational method for inferring competing endogenous interactions. AB - Posttranscriptional cross talk and communication between genes mediated by microRNA response element (MREs) yield large regulatory competing endogenous RNA (ceRNA) networks. Their inference may improve the understanding of pathologies and shed new light on biological mechanisms. A variety of RNA: messenger RNA, transcribed pseudogenes, noncoding RNA, circular RNA and proteins related to RNA induced silencing complex complex interacting with RNA transfer and ribosomal RNA have been experimentally proved to be ceRNAs. We retrace the ceRNA hypothesis of posttranscriptional regulation from its original formulation [Salmena L, Poliseno L, Tay Y, et al. Cell 2011;146:353-8] to the most recent experimental and computational validations. We experimentally analyze the methods in literature [Li J-H, Liu S, Zhou H, et al. Nucleic Acids Res 2013;42:D92-7; Sumazin P, Yang X, Chiu H-S, et al. Cell 2011;147:370-81; Sarver AL, Subramanian S. Bioinformation 2012;8:731-3] comparing them with a general machine learning approach, called ceRNA predIction Algorithm, evaluating the performance in predicting novel MRE-based ceRNAs. PMID- 27677961 TI - Corrigendum: Terahertz radiation driven by two-color laser pulses at near relativistic intensities: Competition between photoionization and wakefield effects. PMID- 27677960 TI - Unraveling chloroplast transcriptomes with ChloroSeq, an organelle RNA-Seq bioinformatics pipeline. AB - Online sequence repositories are teeming with RNA sequencing (RNA-Seq) data from a wide range of eukaryotes. Although most of these data sets contain large numbers of organelle-derived reads, researchers tend to ignore these data, focusing instead on the nuclear-derived transcripts. Consequently, GenBank contains massive amounts of organelle RNA-Seq data that are just waiting to be downloaded and analyzed. Recently, a team of scientists designed an open-source bioinformatics program called ChloroSeq, which systemically analyzes an organelle transcriptome using RNA-Seq. The ChloroSeq pipeline uses RNA-Seq alignment data to deliver detailed analyses of organelle transcriptomes, which can be fed into statistical software for further analysis and for generating graphical representations of the data. In addition to providing data on expression levels via coverage statistics, ChloroSeq can examine splicing efficiency and RNA editing profiles. Ultimately, ChloroSeq provides a well-needed avenue for researchers of all stripes to start exploring organelle transcription and could be a key step toward a more thorough understanding of organelle gene expression. PMID- 27677962 TI - Loss of second and sixth conserved cysteine residues from trypsin inhibitor-like cysteine-rich domain-type protease inhibitors in Bombyx mori may induce activity against microbial proteases. AB - Previous studies have indicated that most trypsin inhibitor-like cysteine-rich domain (TIL)-type protease inhibitors, which contain a single TIL domain with ten conserved cysteines, inhibit cathepsin, trypsin, chymotrypsin, or elastase. Our recent findings suggest that Cys2nd and Cys6th were lost from the TIL domain of the fungal-resistance factors in Bombyx mori, BmSPI38 and BmSPI39, which inhibit microbial proteases and the germination of Beauveria bassiana conidia. To reveal the significance of these two missing cysteines in relation to the structure and function of TIL-type protease inhibitors in B. mori, cysteines were introduced at these two positions (D36 and L56 in BmSPI38, D38 and L58 in BmSPI39) by site directed mutagenesis. The homology structure model of TIL domain of the wild-type and mutated form of BmSPI39 showed that two cysteine mutations may cause incorrect disulfide bond formation of B. mori TIL-type protease inhibitors. The results of Far-UV circular dichroism (CD) spectra indicated that both the wild type and mutated form of BmSPI39 harbored predominantly random coil structures, and had slightly different secondary structure compositions. SDS-PAGE and Western blotting analysis showed that cysteine mutations affected the multimerization states and electrophoretic mobility of BmSPI38 and BmSPI39. Activity staining and protease inhibition assays showed that the introduction of cysteine mutations dramaticly reduced the activity of inhibitors against microbial proteases, such as subtilisin A from Bacillus licheniformis, protease K from Engyodontium album, protease from Aspergillus melleus. We also systematically analyzed the key residue sites, which may greatly influence the specificity and potency of TIL type protease inhibitors. We found that the two missing cysteines in B. mori TIL type protease inhibitors might be crucial for their inhibitory activities against microbial proteases. The genetic engineering of TIL-type protease inhibitors may be applied in both health care and agricultural industries, and could lead to new methods for breeding fungus-resistant transgenic crops and antifungal transgenic silkworm strains. PMID- 27677963 TI - The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing. AB - BACKGROUND: The clinical outcomes following intrasynovial flexor tendon repair are highly variable. Excessive inflammation is a principal factor underlying the formation of adhesions at the repair surface and affecting matrix regeneration at the repair center that limit tendon excursion and impair tendon healing. A previous in-vitro study revealed that adipose-derived mesenchymal stromal cells (ASCs) modulate tendon fibroblast response to macrophage-induced inflammation. The goal of the current study was therefore to explore the effectiveness of autologous ASCs on the inflammatory stage of intrasynovial tendon healing in vivo using a clinically relevant animal model. METHODS: Zone II flexor tendon transections and suture repairs were performed in a canine model. Autologous ASC sheets were delivered to the surface of repaired tendons. Seven days after repair, the effects of ASCs on tendon healing, with a focus on the inflammatory response, were evaluated using gene expression assays, immunostaining, and histological assessments. RESULTS: ASCs delivered via the cell sheet infiltrated the host tendon, including the repair surface and the space between the tendon ends, as viewed histologically by tracking GFP-expressing ASCs. Gene expression results demonstrated that ASCs promoted a regenerative/anti-inflammatory M2 macrophage phenotype and regulated tendon matrix remodeling. Specifically, there were significant increases in M2-stimulator (IL-4), marker (CD163 and MRC1), and effector (VEGF) gene expression in ASC-sheet treated tendons compared with nontreated tendons. When examining changes in extracellular matrix expression, tendon injury caused a significant increase in scar-associated COL3A1 expression and reductions in COL2A1 and ACAN expression. The ASC treatment effectively counteracted these changes, returning the expression levels of these genes closer to normal. Immunostaining further confirmed that ASC treatment increased CD163+ M2 cells in the repaired tendons and suppressed cell apoptosis at the repair site. CONCLUSIONS: This study provides a novel approach for delivering ASCs with outcomes indicating potential for substantial modulation of the inflammatory environment and enhancement of tendon healing after flexor tendon repair. PMID- 27677964 TI - Serum Galectin-3 Levels Predict Recurrences after Ablation of Atrial Fibrillation. AB - Galectin-3 is a biomarker of fibrosis and atrial remodeling, involved in the mechanisms of initiation and maintenance of atrial fibrillation (AF). We sought to study the accuracy of galectin-3 level in predicting recurrences of AF after ablation. Serum concentrations of galectin-3 were determined in a consecutive series of patients addressed for AF ablation in our center. After a 3-month blanking period, recurrences of atrial arrhythmias were collected during the first year in all patients, using Holter monitoring at 3, 6 months and 12 months. A total of 160 patients were included, with a mean galectin-3 rate was 14.4 +/- 5.6 ng/mL. At 12-month, 55 patients (34%) had reexperienced sustained atrial arrhythmia. Only higher galectin-3 level (HR = 1.07 [1.01-1.12], p = 0.02) and larger left atrial diameter (HR = 1.07 [1.03-1.12], p = 0.001) independently predicted recurrence. Patients with both galectin-3 level <15 ng/mL and left atrial diameter <40 millimeters had a 1-year arrhythmia-free survival rate - after a single procedure without anti-arrhythmic drug - of 91%, as compared with 41% in patients with galectin-3 >= 15 and left trial diameter >=40 (p < 0.0001), whether AF was paroxysmal or persistent. Galectin-3 and left atrial diameters, rather than clinical presentation of AF, predict recurrences after ablation. PMID- 27677965 TI - Relationship Between Meditation Depth and Waking Salivary Alpha-Amylase Secretion Among Long-Term MBSR Instructors. AB - The purpose of this study was to characterize sympathetic activity by using waking salivary alpha-amylase (sAA) concentrations in a group of long-term meditation instructors and to examine the association between meditation (depth, dose and duration) and the waking alpha-amylase response. Salivary alpha-amylase samples were collected (immediately upon waking and at 15-min, 30-min and 45-min intervals after waking) from mindfulness-based stress reduction instructors to determine both the area under the curve and the awakening slope (difference in alpha-amylase concentrations between waking and 30-min post-waking). It was determined through general linear models that neither years of meditation nor meditation dose were associated with the awakening sAA slope, but higher scores for meditation depth (greater depth) was associated with a more negative (or steeper) awakening slope [Quartile (Q)1: -7 versus Q4: -21 U/mL; p = 0.06], in fully adjusted models. Older age (p = 0.04) and a later time of waking (p < 0.01) also were associated with less negative awakening slope values. Smoking was associated with lower area under the curve values (smokers: 1716 U/mL versus nonsmokers: 2107 U/mL; p = 0.05) in fully adjusted models. The results suggest a 'healthy' sAA waking slope among individuals who meditate more deeply. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27677966 TI - Infectious disease: Diagnostic criteria for neurocysticercosis - a difficult update. PMID- 27677967 TI - Neuroendocrinology: Oestrogen therapy affects brain structure but not function. PMID- 27677969 TI - Cytonuclear incompatibility contributes to the early stages of speciation. AB - Genetic incompatibility is a hallmark of speciation. Cytonuclear incompatibilities are proposed to be among the first genetic barriers to arise during speciation. Accordingly, reproductive isolation (RI) within species should be heavily influenced by interactions between the organelle and nuclear genomes. However, there are few clear examples of cytonuclear incompatibility within a species. Here, we show substantial postzygotic RI in first-generation hybrids between differentiated populations of an herbaceous plant (up to 92% reduction in fitness). RI was primarily due to germination and survival, with moderate RI for pollen viability. RI for survival was asymmetric and caused by cytonuclear incompatibility, with the strength of incompatibility linearly related to chloroplast genetic distance. This cytonuclear incompatibility may be the result of a rapidly evolving plastid genome. Substantial asymmetric RI was also found for germination, but was not associated with cytonuclear incompatibility, indicating endosperm or maternal-zygote incompatibilities. These results demonstrate that cytonuclear incompatibility contributes to RI within species, suggesting that initial rates of speciation could be influenced by rates of organelle evolution. However, other genetic incompatibilities are equally important, indicating that even at early stages, speciation can be a complex process involving multiple genes and incompatibilities. PMID- 27677968 TI - Characterization of four vaccine-related polioviruses including two intertypic type 3/type 2 recombinants associated with aseptic encephalitis. AB - BACKGROUND: Four vaccine-related polioviruses (VRPV) were isolated from aseptic encephalitis cases in Yunnan, China in 2010. The genomic sequences of these VRPVs were investigated to gain a better understanding of their molecular characteristics. METHODS: Molecular typing was performed by amplification and sequencing of the VP1 region. The genomic sequences of the four VRPV3 strains were compared to vaccine strain and wild strain sequences to study genetic drift and recombination. RESULTS: All four isolates could be entirely neutralized by polyclonal poliovirus 3 (PV3) antisera but not by PV1 and PV2 antisera and displayed a temperature-sensitive phenotype. The genomic sequences of all four isolates contained two Sabin 3-specific attenuating mutations at nucleotides 472(C -> T) and 2034(C -> T), but a third Sabin 3-specific attenuating mutation at position 2493 (T -> C) had reverted back to a T. Recombination analyses showed RF108/YN/CHN/2010 and RF134/YN/CHN/2010 strain recombined with Sabin 2 at the 3' end of the 2C to 3'-untranslated region (3'-UTR) and at the 5'-end of the 3D to 3'-UTR, respectively. CONCLUSION: Four VRPV3 strains including two type 3/type 2 intertypic recombinants were identified. The recombination of Sabin vaccine strains with other Sabin serotypes or human enterovirus C species could be a critical factor in the potential of emerging viruses and related disease outbreaks. Therefore, it is essential to be persistent in the surveillance of EVs (including PV). PMID- 27677970 TI - Ullmann-like reactions for the synthesis of complex two-dimensional materials. AB - Engineering two-dimensional materials through surface-confined synthetic techniques is a promising avenue for designing new materials with tailored properties. Developing and understanding reaction mechanisms for surface-confined synthesis of two-dimensional materials requires atomic-level characterization and chemical analysis. Beggan et al (2015 Nanotechnology 26 365602) used scanning tunneling microscopy and x-ray photoelectron spectroscopy to elucidate the formation mechanism of surface-confined Ullmann-like coupling of thiophene substituted porphyrins on Ag(111). Upon surface deposition, bromine is dissociated and the porphyrins couple with surface adatoms to create linear strands and hexagonally packed molecules. Annealing the sample results in covalently-bonded networks of thienylporphyrin derivatives. A deeper understanding of surface-confined Ullmann-like coupling has the potential to lead to precision-engineered nano-structures through synthetic techniques. PMID- 27677971 TI - Sustainably powering wearable electronics solely by biomechanical energy. AB - Harvesting biomechanical energy is an important route for providing electricity to sustainably drive wearable electronics, which currently still use batteries and therefore need to be charged or replaced/disposed frequently. Here we report an approach that can continuously power wearable electronics only by human motion, realized through a triboelectric nanogenerator (TENG) with optimized materials and structural design. Fabricated by elastomeric materials and a helix inner electrode sticking on a tube with the dielectric layer and outer electrode, the TENG has desirable features including flexibility, stretchability, isotropy, weavability, water-resistance and a high surface charge density of 250 MUC m-2. With only the energy extracted from walking or jogging by the TENG that is built in outsoles, wearable electronics such as an electronic watch and fitness tracker can be immediately and continuously powered. PMID- 27677972 TI - Social interactions in bacterial cell-cell signaling. AB - Cooperation and conflict in microorganisms is being recognized as an important factor in the organization and function of microbial communities. Many of the cooperative behaviors described in bacteria are governed through a cell-cell signaling process generally termed quorum sensing. Communication and cooperation in diverse microorganisms exhibit predictable trends that behave according to social evolutionary theory, notably that public goods dilemmas produce selective pressures for divergence in social phenotypes including cheating. In this review, we relate the general features of quorum sensing and social adaptation in microorganisms to established evolutionary theory. We then describe physiological and molecular mechanisms that have been shown to stabilize cooperation in microbes, thereby preventing a tragedy of the commons. Continued study of the role of communication and cooperation in microbial ecology and evolution is important to clinical treatment of pathogens, as well as to our fundamental understanding of cooperative selection at all levels of life. PMID- 27677973 TI - Current State of Child Health in Rural America: How Context Shapes Children's Health. AB - PURPOSE: Children's health is influenced by the context in which they live. We provide a descriptive essay on the status of children in rural America to highlight features of the rural environment that may affect health. DESCRIPTION: We compiled information concerning components of the rural environment that may contribute to health outcomes. Areas addressed include the economic characteristics, provider availability, uniquely rural health risks, health services use, and health outcomes among rural children. ASSESSMENT: Nearly 12 million children live in the rural United States. Rural counties are economically disadvantaged, leading to higher rates of poverty among rural versus urban children. Rural and urban children are approximately equally likely to be insured, but Medicaid insures a higher proportion of children in rural areas. While generally similar in health, rural children are more likely to be overweight or obese than urban children. Rural parents are less likely to report that their children received preventive medical or oral health visits than urban parents. Rural children are more likely to die than their urban peers, largely due to unintentional injury. CONCLUSION: Improving rural children's health will require both increased public health surveillance and research that creates solutions appropriate for rural environments, where health care professionals may be in short supply. Most importantly, solutions must be multisectoral, engaging education, economic development, and other community perspectives as well as health care. PMID- 27677974 TI - Step Sequence Is a Critical Gait Parameter of Unilateral 6-OHDA Parkinson's Rat Models. AB - Parkinson's disease is a progressive neurological disorder, marked by the loss of dopaminergic neurons in the nigrostriatal pathway that leads to abnormal gait, rigidity, slowness of movement, and tremor. The ability to recapitulate and measure the neurological sequelae in rodent models of Parkinson's disease is important for studying and evaluating potential therapeutics. Individual variability in lesion severity and injury progression are key factors in the 6 hydroxydopamine model that require normalization when evaluating therapeutic effects. The gait parameters that were found to be affected by 6-hydroxydopamine lesioning of the nigrostriatal pathway in rats may be used to study novel transgenic models of Parkinson's disease as well as to test novel therapeutics. Previously, studies have used a video-based system to analyze gait abnormalities in the 6-hydroxydopamine model of Parkinson's disease, but these studies did not account for individual variability on reported gait parameters. By analyzing the ratio of parameters from the injured to uninjured sides and correcting for speed in related parameters, hindpaw step cycle parameters, hindpaw print area, and step sequence are significantly altered in different ways for each type of lesion, when compared to saline-injected controls. These findings enable new metrics for evaluating therapeutic efficacy of drug-, gene-, or cell-based therapies in rat models of Parkinson's disease. PMID- 27677975 TI - Perfluoroalkylphosphinic Acids in Northern Pike (Esox lucius), Double-Crested Cormorants (Phalacrocorax auritus), and Bottlenose Dolphins (Tursiops truncatus) in Relation to Other Perfluoroalkyl Acids. AB - Perfluoroalkyl phosphinic acids (PFPIAs) are perfluoroalkyl acids (PFAAs) that are used for their surfactant properties in a variety of applications, resulting in their presence in environmental waters; however, they have not been widely studied in biota. A survey of PFPIAs was conducted in fish, dolphins, and birds from various locations in North America. Northern pike (Esox lucius) were collected at two locations in 2011 near Montreal Island in the St. Lawrence River, Canada, double-crested cormorants (Phalacrocorax auritus) were collected from bird colonies in the Great Lakes in 2010-2012, and bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, FL and Charleston Harbor, SC were sampled in 2004-2009. PFPIAs had a detection frequency of 100% in all animals. This is the first report of PFPIAs in fish, dolphin, and bird plasma. Total PFPIA levels (mean +/- standard deviation, 1.87 +/- 2.17 ng/g wet weight (ww), range of 0.112 15.3 ng/g ww) were 1-2 orders of magnitude lower than those of perfluoroalkyl carboxylates (PFCA) and perfluoroalkanesulfonates (PFSA) in the same samples. The predominant congeners were 6:8 PFPIA (cormorants and pike) and 6:6 PFPIA (dolphins). Total PFPIAs in cormorants from Hamilton Harbour (5.02 +/- 2.80 ng/g ww) were statistically higher than in other areas and taxonomic groups. The ubiquity of PFPIAs warrants further research on sources and effects of these unique compounds. PMID- 27677976 TI - Determination of Hexachlorocyclohexane by Gas Chromatography Combined with Femtosecond Laser Ionization Mass Spectrometry. AB - Structural isomers and enantiomers of hexachlorocyclohexane (HCH) were separated using a chiral column by gas chromatography and quantitatively determined by multiphoton ionization mass spectrometry using an ultraviolet femtosecond laser (200 and 267 nm) as the ionization source. The order of elution of the enantiomers (i.e., (+)-alpha-HCH and (-)-alpha-HCH) was predicted from stabilization energies calculated for the complexes using permethylated gamma cyclodextrin as the stationary phase of the column, and the results were compared with the experimental data. The molecular ions observed for HCH were weak, even though they can be ionized through a process of resonance enhanced two-photon ionization at 200 nm. This unfavorable result can be attributed to the dissociation of the molecular ion, as predicted from quantum chemical calculations. Graphical Abstract ?. PMID- 27677977 TI - Quality of life in children with chronic kidney disease. AB - BACKGROUND: Progressive chronic kidney disease (CKD), irrespective of the underlying etiology, affects the quality of life (QoL) of children due to the need for regular follow-up visits, a strict medication program and diet intake. METHODS: The Greek version of the KIDSCREEN-52 multidimensional questionnaire was used in children with CKD, renal transplantation (RT) and in a control group (CG) of healthy children. RESULTS: Fifty-five patients between 8 and 18 years, with CKD (n = 25), RT (n = 16) and with end-stage renal disease (ESRD) on peritoneal dialysis (PD) (n = 14) were included. Each group of studied children was compared with the CG (n = 55), the validation sample (VS) (n = 1200) and the parent proxy scores. Physical well-being of all studied children was significantly lower compared to CG (p = 0.004). In contrast, all studied children between 8 and 11 years showed better social acceptance compared to VS (p = 0.0001). When QoL of children with CKD was compared with parent proxy QoL, conflicting opinions were observed in several dimensions, such as self-perception (p = 0.023), autonomy (p = 0.012), school environment (p = 0.012) and financial resources (p = 0.03). CONCLUSIONS: QoL and mainly the dimension of physical well-being, may be affected dramatically in children with CKD unrelated to disease stage. In early school years children with CKD seem to feel higher social acceptance than the healthy controls, exhibiting better score in this dimension. Optimal care requires attention not only to medical management, but also to an assessment of QoL factors, that may help promote pediatric patient's health. PMID- 27677978 TI - Use of a low-dose prednisolone regimen to treat a relapse of steroid-sensitive nephrotic syndrome in children. AB - BACKGROUND: Relapses of nephrotic syndrome are common and are treated with a course of prednisolone (2 mg/kg/day or 60 mg/m2/day). This is associated with major adverse effects including diabetes, weight gain, hypertension and behavioural problems. This study is a retrospective review examining the success of treating relapses in steroid-sensitive nephrotic syndrome (SSNS) with low-dose prednisolone and the consequences on subsequent relapse rates. Furthermore, a follow-up study looked at the side-effect profile during treatment with high- versus low-dose prednisolone. METHODS: Between January 2012 and July 2013, all well children with SSNS presenting with a relapse were advised to start 1 mg/kg prednisolone daily for a maximum of 7 days. In July 2015, we compared the side effect profile of prednisolone therapy using the parent proxy PedsQL questionnaire for quality of life (QoL). RESULTS: Fifty patients were included in the study, with a total of 87 relapses. Sixty-one of the 87 relapses (70 %) responded within a week. Treating relapses with a reduced dose of steroids did not adversely affect the relapse rate in the 6 months preceding and following the current relapse (1.01 vs 0.86, p = 0.3). Fifteen parents completed the PedsQL questionnaire. Comparison of scores in each category showed significantly higher values in each domain during treatment with low-dose prednisolone compared with high-dose treatment (35.6 vs 18.3, p < 0.0001; 31.1 vs 15.0, p < 0.001; 38.3 vs 20.1, p < 0.0001). CONCLUSION: A low-dose prednisolone regimen was successful in achieving remission in 70 % of relapses of children with SSNS, without adversely affecting the relapse rate. Parent-completed QoL questionnaires showed significantly higher scores on low-dose treatment, indicating better QoL. PMID- 27677979 TI - Clinical presentation and outcome of pediatric ANCA-associated glomerulonephritis. AB - BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a small- and medium-sized vasculitis classically seen in adult patients, with peak onset near the fifth to seventh decade of life. There is little data on ANCA associated vasculitis in pediatric patients, and most studies have limited follow up. METHODS: This is a retrospective chart review of 22 patients with ANCA positive glomerulonephritis in a single institution from 1991 to 2013. RESULTS: Of the 22 patients, eight (36 %) required renal replacement therapy (RRT) at diagnosis; four of these patients recovered sufficient renal function to initially discontinue dialysis. Five patients (23 %) were treated with plasmapheresis at presentation. The median time from presentation until first clinical or serologic relapse was 1.7 +/- 1.2 years. After a median follow-up of 5.8 years, just over half of our patients had chronic kidney disease (CKD) stages 1-3 (55 %). Seven (32 %) patients progressed to end-stage renal disease (ESRD) and eventually required kidney transplant. CONCLUSION: ANCA-associated glomerulonephritis is a rare disorder in children. Presentation and outcomes vary significantly among patients. More research is required to follow these patients who are diagnosed in childhood to further characterize the long-term outcome of the disease. PMID- 27677980 TI - Combined use of renin-angiotensin-aldosterone system-acting agents: a cross sectional study. AB - Background Due to recent EU warnings and restrictions on the combined use of renin-angiotensin-aldosterone system (RAAS)-acting agents, and the seriousness of the associated harm, we analyzed the prescription of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as dual therapy or associated with spironolactone. Setting An administrative claims database of a regional hospital in Romania. Methods We retrospectively included all adult patients hospitalized during 18 months in 2013-2014, discharged with a prescription of a RAAS-acting agent. Main outcome measures Counts of ACEIs and ARBs co-prescription, of ACEIs or ARBs combined with spironolactone, co morbidities, co-medication, creatinine, and electrolytes assessment and values. Results Out of 1697 patients with a prescription of a RAAS-acting agent, 24 (1.4 %) were co-prescribed ACEIs and ARBs, and 416 (24.5 %) ACEIs or ARBs with spironolactone. Patients prescribed dual ACEI/ARB therapy and the ones with ACEI or ARB-spironolactone combination had significantly higher prevalence of increased creatinine level before discharge, compared to the ACEI and ARB monotherapy groups (48 and 31 % compared to 17 and 27 %). Subjects with diabetes, heart failure, ischaemic heart disease, or urea >=40 mg/dL had higher odds of having ACEI or ARB-spironolactone combination compared to monotherapy, while hypertension and renal disease subjects had lower odds. Similar findings were comparing dual ACEI/ARB therapy to monotherapy except heart failure (not statistically significant). Conclusion Overall, the prevalence of use of dual therapy was low. The combined use of RAAS-acting agents was higher in patients with known risk factors for further renal function deterioration, compared to the ones without. PMID- 27677981 TI - Role of positron emission tomography imaging in Multiple Endocrine Neoplasia syndromes. AB - The aim of this review was to summarize the recent developments on the role of positron emission tomography (PET) imaging using different radiopharmaceuticals in patients with multiple endocrine neoplasia (MEN) syndromes. Although most guidelines do not mention the use of PET imaging in patients with MEN syndromes, recent data seem to suggest a relevant diagnostic role of PET imaging in this setting. In particular, latest evidence has shown that somatostatin receptor PET provides a diagnostic accuracy in detecting MEN syndromes-related neuroendocrine tumours (NETs) higher than that of somatostatin receptor scintigraphy, thus influencing patient management in a significant percentage of cases. 18 F-DOPA PET seems to have a potential role in detecting MEN-2-related NETs, whereas 18 F FDG PET is potentially useful in identifying aggressive NETs with poorer outcomes. More studies are needed to better define the role of different radiotracer-based PET imaging in patients with MEN syndromes. PMID- 27677982 TI - Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats. AB - The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection. PMID- 27677984 TI - Mid-term results of Oxford phase-3 medial unicompartmental knee arthroplasty for medial arthritis in Chinese patients. AB - BACKGROUND: The purpose of this study was to evaluate the mid-term results of an Oxford phase-3 unicompartmental knee arthroplasty (UKA) for medial arthritis in Chinese patients. METHODS: The study included 64 patients who underwent a minimally invasive Oxford phase-3 UKA for medial knee arthritis. The patients were clinically evaluated preoperatively and at the final follow-up according to the clinical and functional components of the Knee Society Score (KSS), the Hospital for Special Surgery knee score and range of motion. A Kaplan-Meier survivorship analysis was performed with revision surgery as the end point. RESULTS: The mean preoperative clinical KSSs increased from 63.2 to 91.4 post operatively, and the mean functional KSSs increased from 54.9 to 86.5 post operatively. In addition, the mean Hospital for Special Surgery scores increased from 59.5 to 86.4. The mean active knee flexion increased from 109.1 degrees preoperatively to 123.6 degrees post-operatively. A total of six patients (six knees) required revision surgery at the time of the maximum 10-year follow-up. Four conversions to total knee arthroplasty were performed because of arthritis progression in the lateral compartment. One revision to total knee arthroplasty was performed for aseptic loosening, and one liner exchange was performed for wear. The cumulative survival rates at the 6- and 8-year follow-ups were 97% and 93%, respectively. CONCLUSION: Oxford phase-3 UKA was largely applicable for medial arthritis in Chinese patients. However, the Oxford phase-3 medial UKA selection criteria for young Chinese males need further exploration to obtain the best treatment effect. PMID- 27677983 TI - The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 4: Unmet Needs in the Treatment of Bipolar Disorder and Recommendations for Future Research. AB - Background: The current fourth paper on the International College of Neuropsychopharmacology guidelines for the treatment of bipolar disorder reports on the unmet needs that became apparent after an extensive review of the literature and also serves as a conclusion to the project of the International College of Neuropsychopharmacology workgroup. Materials and Methods: The systematic review of the literature that was performed to develop the International College of Neuropsychopharmacology guidelines for bipolar disorder identified and classified a number of potential shortcomings. Results: Problems identified concerned the reliability and validity of the diagnosis of bipolar disorder and especially of bipolar depression. This, in turn, has profound consequences for early detection and correct treatment of the disorder. Another area that needs improvement is the unsatisfactory efficacy and effectiveness of therapeutic options, especially in special populations such as those with mixed features and rapid cycling course. Gender issues and adherence problems constitute an additional challenge. The literature suggests that while treatment providers are concerned more with treatment-related issues, patients and their caregivers worry more about issues pertaining to the availability of services and care, quality of life, and various types of burden. The workgroup identified additional unmet needs related to the current standard of research in bipolar disorder. These include the fragmentation of bipolar disorder into phases that are handled as being almost absolutely independent from each other, and thus the development of an overall therapeutic strategy on the basis of the existing evidence is very difficult. Trials are not always designed in a way that outcomes cover the most important aspects of bipolar disorder, and often the reporting of the results is biased and unsatisfactory. The data on combination treatments and high dosages are sparse, whereas they are common in real world practice. Conclusions: The workgroup endorses the full release of raw study data to the scientific community, and the development of uniform clinical trial standards (also including more realistic outcomes) and the reporting of results. The 2 large appendices summarize the results of this systematic review with regard to the areas of lack of knowledge where further focused research is necessary. PMID- 27677985 TI - A Threshold Dosage of Testosterone for Female-to-Male Sex Reversal in Rana rugosa Frogs. AB - Androgens play a critical role in testicular differentiation in many species of vertebrates. While female-to-male sex reversal can be induced by testosterone (T) in some species of amphibians, the mechanism still remains largely unknown even at the histological level. In this study, we determined a threshold dosage of T to induce female-to-male sex reversal in the Japanese frog Rana (R.) rugosa. Tadpoles were allowed to metamorphose into frogs with T present in the rearing water. At 0.2 ng/mL T, female frogs formed tissue comprising a mixture of ovary and testis, the so-called ovotestis, the size of which was significantly smaller than the wild-type ovary. Histological changes occurring in the oocytes of T treated ovaries induced oocyte degeneration in the masculinizing ovaries leading to their final disappearance. In parallel, many germ cells emerged in the cortex of the ovotestis and, later, in the medulla as well. RT-PCR analysis revealed upregulated expression of CYP17 and Dmrt1 but not 17betaHSD in the ovotestis, and downregulation of Pat1a expression. Furthermore, immunohistology revealed CYP17 positive signals in the cortex of the masculinizing ovary, spreading throughout the whole area as the testis developed. These results indicate that oocytes are sensitive to T in the ovary of R. rugosa and that male-type germ cells expand in the masculinizing gonad (testis) contemporaneous with oocyte disappearance. PMID- 27677987 TI - Hygroscopic study of hydroxypropylcellulose : Structure and strain-induced birefringence of capillary bridges. AB - The hygroscopic method developed previously for studies of lyotropic liquid crystals is used for the first time in experiments with millimetric capillary bridges made of a hydroxypropylcellulose/water mixture. Composition of such very small samples is controlled via humidity of the surrounding air. By a slow and well-controlled drying of initially isotropic samples, the isotropic/anisotropic phase transition is crossed and polydomain pseudo-isotropic capillary bridges are prepared. Kept in an atmosphere of constant humidity, these bridges are stretched and the strain-induced birefringence [Formula: see text] n is measured as a function of the draw ratio [Formula: see text] . The variation of [Formula: see text] n with [Formula: see text] is interpreted in terms of an affine uniaxial deformation of the initial pseudo-isotropic texture. PMID- 27677986 TI - Ethylene-Regulated Glutamate Dehydrogenase Fine-Tunes Metabolism during Anoxia Reoxygenation. AB - Ethylene is an essential hormone in plants that is involved in low-oxygen and reoxygenation responses. As a key transcription factor in ethylene signaling, ETHYLENE INSENSITIVE3 (EIN3) activates targets that trigger various responses. However, most of these targets are still poorly characterized. Through analyses of our microarray data and the published Arabidopsis (Arabidopsis thaliana) EIN3 chromatin immunoprecipitation sequencing data set, we inferred the putative targets of EIN3 during anoxia-reoxygenation. Among them, GDH2, which encodes one subunit of glutamate dehydrogenase (GDH), was chosen for further studies for its role in tricarboxylic acid cycle replenishment. We demonstrated that both GDH1 and GDH2 are induced during anoxia and reoxygenation and that this induction is mediated via ethylene signaling. In addition, the results of enzymatic assays showed that the level of GDH during anoxia-reoxygenation decreased in the ethylene-insensitive mutants ein2-5 and ein3eil1 Global metabolite analysis indicated that the deamination activity of GDH might regenerate 2-oxoglutarate, which is a cosubstrate that facilitates the breakdown of alanine by alanine aminotransferase when reoxygenation occurs. Moreover, ineffective tricarboxylic acid cycle replenishment, disturbed carbohydrate metabolism, reduced phytosterol biosynthesis, and delayed energy regeneration were found in gdh1gdh2 and ethylene mutants during reoxygenation. Taken together, these data illustrate the essential role of EIN3-regulated GDH activity in metabolic adjustment during anoxia reoxygenation. PMID- 27677988 TI - Adsorption behaviors of fungicide-derived copper onto various size fractions of aggregates from orchard soil. AB - Although the gradual accumulations of Cu in orchard soils due to the application of Cu-based fungicides have been widely reported, limited information is available about the retention characteristics of fungicide-derived Cu in soil, especially in various size soil aggregates. This study described the adsorption characteristics of Cu from commonly used fungicide, Bordeaux mixture (CuSO4 + Ca(OH)2), onto various aggregate fractions (2000-1000, 1000-500, 500-250, 250 106, and <106 MUm) of orchard soil. The Cu(NO3)2 was selected as a comparison. Two different types of adsorption experiments were conducted as follows: variable pH and variable Cu concentration experiments. The adsorption processes of Bordeaux mixture and Cu(NO3)2 onto the studied soil samples followed well with the Freundlich isotherm, and the adsorption isotherms were the S shaped. The adsorption amounts of Cu from different Cu compounds differed, and Bordeaux mixture can result in more Cu retention in soil than Cu(NO3)2. The adsorption ability of different size soil aggregates varied, and it was mainly governed by soil properties. The findings of this study suggested that both the chemical compositions of Cu compounds and the soil physical structure should be taken into account when performing soil Cu retention experiments with fungicide-derived Cu. PMID- 27677989 TI - Magnetically recoverable TiO2-WO3 photocatalyst to oxidize bisphenol A from model wastewater under simulated solar light. AB - A novel magnetically recoverable, visible light active TiO2-WO3 composite (Fe3O4@SiO2@TiO2-WO3) was prepared to enable the photocatalyst recovery after the degradation of bisphenol A (BPA) under simulated solar light. For comparison, the photocatalytic activity of other materials such as non-magnetic TiO2-WO3, Fe3O4@SiO2@TiO2, TiO2, and the commercial TiO2 P25 was also evaluated under the studied experimental conditions. The structure and morphology of the synthesized materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), and electron dispersion spectroscopy (EDS). Moreover, Brunauer-Emmett-Teller (BET) surface area and magnetic properties of the samples were determined. The Fe3O4@SiO2@TiO2-WO3 and TiO2-WO3 led to a BPA degradation of 17.50 and 27.92 %, respectively, after 2 h of the simulated solar light irradiation. Even though their activity was lower than that of P25, which degraded completely BPA after 1 h, our catalysts were magnetically separable for their further reuse in the treatment. Furthermore, the influence of the water matrix in the photocatalytic activity of the samples was studied in municipal wastewater. Finally, the identification of reaction intermediates was performed and a possible BPA degradation pathway was proposed to provide a better understanding of the degradation process. Graphical abstract ?. PMID- 27677990 TI - Competitive adsorption of phthalate esters on marine surface sediments: kinetic, thermodynamic, and environmental considerations. AB - In this study, the sorption behavior of six widely used phthalate esters (PEs) on marine sediments was investigated. The adsorption of PEs was fast and reached the equilibrium within 6 h. The forward and backward rate constants of all PEs on sediments were calculated. Several kinds of kinetic and thermodynamic models have been investigated; the pseudo-second-order model and the partition isotherm model were best fitted to the adsorption behavior of PEs. The rate-limiting step of sorption was controlled by the film diffusion mechanism. After treating sediments with H2O2, the partition coefficients of all PEs were significantly reduced and indicated that the amorphous organic carbon has a major role in adsorption process. The negative values of DeltaH degrees and DeltaG degrees for these compounds showed that the sorption process is exothermic and spontaneous. The adsorption capacities of all PEs were slightly influenced by increasing the salinity from 0 to 40 g L-1. These research findings have a prime importance on assessment of the fate and transport of PEs in seawater-sediment systems. PMID- 27677991 TI - Assessment of diesel-contaminated domestic wastewater treated by constructed wetlands for irrigation of chillies grown in a greenhouse. AB - In order to avoid environmental pollution and eliminate the need for using fertiliser, this study assessed for the first time the optimum performance of mature (in operation since 2011) vertical flow constructed wetlands in treating domestic wastewater (with and without hydrocarbon) and the subsequent recycling of the outflow to irrigate chillies (De Cayenne; Capsicum annuum (Linnaeus) Longum Group 'De Cayenne') grown in a greenhouse. Various variables were investigated to assess the treatment performance. Concerning chilli fruit numbers, findings showed that the highest fruit yields for all wetland filters were associated with those that received inflow wastewater with a high loading rate, reflecting the high nutrient availability in treated wastewater, which is of obvious importance for yield production. Findings also indicated that wetlands without hydrocarbon, small aggregate size, low contact time and low inflow loading rate provided high marketable yields (expressed in economic return). In comparison, chillies irrigated by filters with hydrocarbon contamination, small aggregate size, high contact time and high loading rate also resulted in high marketable yields of chillies, which pointed out the role of high contact time and high inflow load for better diesel degradation rates. PMID- 27677992 TI - Biostimulation proved to be the most efficient method in the comparison of in situ soil remediation treatments after a simulated oil spill accident. AB - The use of in situ techniques in soil remediation is still rare in Finland and most other European countries due to the uncertainty of the effectiveness of the techniques especially in cold regions and also due to their potential side effects on the environment. In this study, we compared the biostimulation, chemical oxidation, and natural attenuation treatments in natural conditions and pilot scale during a 16-month experiment. A real fuel spill accident was used as a model for experiment setup and soil contamination. We found that biostimulation significantly decreased the contaminant leachate into the water, including also the non-aqueous phase liquid (NAPL). The total NAPL leachate was 19 % lower in the biostimulation treatment that in the untreated soil and 34 % lower in the biostimulation than oxidation treatment. Soil bacterial growth and community changes were first observed due to the increased carbon content via oil amendment and later due to the enhanced nutrient content via biostimulation. Overall, the most effective treatment for fresh contaminated soil was biostimulation, which enhanced the biodegradation of easily available oil in the mobile phase and consequently reduced contaminant leakage through the soil. The chemical oxidation did not enhance soil cleanup and resulted in the mobilization of contaminants. Our results suggest that biostimulation can decrease or even prevent oil migration in recently contaminated areas and can thus be considered as a potentially safe in situ treatment also in groundwater areas. PMID- 27677993 TI - Assessing anthropogenic levels, speciation, and potential mobility of rare earth elements (REEs) in ex-tin mining area. AB - A study was carried out to determine the level of rare earth elements (REEs) in water and sediment samples from ex-mining lakes and River in Kinta Valley, Perak, Malaysia. Surface water and sediments from an ex-mining lake and Kinta River water samples were analyzed for REEs by inductively coupled plasma mass spectrometry. The total concentration of REEs in the ex-mining lake water samples and sediments were found to be 3685 mg/l and 14159 mg/kg, respectively, while the total concentration of REEs in Kinta River water sample was found to be 1224 mg/l. REEs in mining lake water were found to be within 2.42 mg/l (Tb) to 46.50 mg/l (Ce), while for the Kinta River, it was 1.33 mg/l (Ho) to 29.95 mg/l (Ce). Sediment samples were also found with REEs from 9.81 mg/kg (Ho) to 765.84 mg/kg (Ce). Ce showed the highest average concentrations for mining lake (3.88 to 49.08 mg/l) and Kinta River (4.44 to 33.15 mg/l) water samples, while the concentration of La was the highest (11.59 to 771.61 mg/kg) in the mining lake sediment. Lu was shown to have the highest enrichment of REEs in ex-mining lake sediments (107.3). Multivariate statistical analyses such as factor analysis and principal component analysis indicated that REEs were associated and controlled by mixed origin, with similar contributions from anthropogenic and geogenic sources. The speciation study of REEs in ex-tin mining sediments using a modified five-stage sequential extraction procedure indicated that yttrium (Y), gadolinium (Gd), and lanthanum (La) were obtained at higher percentages from the adsorbed/exchanged/carbonate fraction. The average potential mobility of the REEs was arranged in a descending order: Yb > Gd > Y = Dy > Pr > Er > Tm > Eu > Nd > Tb > Sc > Lu > Ce > La, implying that under favorable conditions, these REEs could be released and subsequently pollute the environment. PMID- 27677994 TI - Accumulation behavior and risk assessment of heavy metals and arsenic in tissues of white bream (Parabramis pekinensis) from the Xiang River, southern China. AB - Aquatic environment suffered from serious heavy metal and As pollutions due to rapid industrialization and urbanization in the last decades. In order to evaluate the heavy metal and As contamination in aquatic organism in southern China, the levels of As, Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn in muscle, gill, and liver of white bream (Parabramis pekinensis) collected from Xiang River were analyzed. The statistically significant differences of the analyzed element concentration (wet weight) between tissues were determined through one-way analysis of variance (ANOVA). The liver presented high affinity for accumulation of Cd, Cu, and Zn due to the binding activity of metallothionein proteins. Mn and Pb mainly accumulated in the gill indicated the major uptake route through the gill. Lack of correlation between analyzed element and fish size might imply no or weak biomagnification of the analyzed elements in fish tissues. The potential health risk associated with exposure to heavy metals and As was evaluated. The uncertainty of target hazard quotient was calculated by Monte Carlo simulation. The results indicated that the analyzed element contents in the white bream muscle posed relatively low-chronic toxic risk to consumers. PMID- 27677995 TI - Biomonitoring of tobacco smoke exposure and self-reported smoking status among general population of Tehran, Iran. AB - The present study aimed to find a correlation between the self-reported smoking status of the residents of Tehran, Iran, and the urine cotinine as a biomarker of exposure to tobacco smoke. The self-reported data was collected from 222 participants who were living in the urban area of Tehran. The urine samples of participants were collected for cotinine analysis. Urine cotinine was measured by an enzymatic immunoassay technique. Tobacco smoking was reported by 76 (34.23 %) participants as the self-reported data, and the number of males in this report was higher than of females (p < 0.001). By adding the number of the self-reported non-smokers with cotinine levels above the cutoff value of >100 ng/ml to self reported smokers, the smoking prevalence increased from 34.23 % (95 % CI 28.01 40.88 %) to 36.48 % (95 % CI 30.14-43.19 %). Using the cutoff value, sensitivity and specificity of the self-reported smoking status were respectively 90.12 % (95 % CI 81.46-95.64 %) and 98 % (95 % CI 93.91-99.55 %). The levels of agreement between self-reported tobacco smoking and urinary cotinine concentrations was 95.1 % (k = 0.89, p < 0.001, 95 % CI = 0.81-0.95). Based on the results, self reported smoking can be a valid marker for assessing the tobacco exposure, and it can be of use in large epidemiological studies. PMID- 27677996 TI - Slow-release nitrogen fertilizers can improve yield and reduce Cd concentration in pakchoi (Brassica chinensis L.) grown in Cd-contaminated soil. AB - Cadmium (Cd) pollution in vegetable crops has become a serious problem in recent years. Owing to the limited availability of arable land resources, large areas of Cd-contaminated lands are inevitably being used for the production of vegetables, posing great risks to human health via the food chain. However, strategies to improve yield and reduce Cd concentration in crops grown in contaminated soils are being developed. In the present study, using pot experiments, we investigated the effects of two slow-release nitrogen fertilizers (SRNFs), resin-coated ammonium nitrate (Osmocote313s), and resin-coated urea (urea620), on the growth and Cd concentration of the Cd-contaminated pakchoi. The results showed that pakchoi grown in soil containing 5 mg kg-1 of Cd-induced oxidative stress (indicated by malondialdehyde (MDA), H2O2, and O2.-) and photosynthesis inhibition, which in turn was restored with the application of SRNFs. However, pakchoi grown in Cd-contaminated soil supplied with Osmocote313s and urea620 showed 103 and 203 % increase in fresh weight and 51-55 % and 44-56 % decrease in Cd concentration, respectively, as compared with their controls (pakchoi treated with instant soluble nitrogen fertilizers). On the basis of an increase in their tolerance index (47-238 %) and a decrease in their translocation factor (7.5-21.6 %), we inferred that the plants treated with SRNFs have a stronger tolerance to Cd and a lower efficiency of Cd translocation to edible parts than those treated with instant soluble nitrogen fertilizers. Therefore, in terms of both crop production and food safety, application of SRNFs could be an effective strategy for improving both biomass production and quality in pakchoi grown under Cd stress. PMID- 27677997 TI - Adsorption behavior of tetracycline by extracellular polymeric substrates extracted from Klebsiella sp. J1. AB - The extracellular polymeric substrate (EPS) extracted from Klebsiella sp. J1 was used to adsorb low concentrations of tetracycline, and the efficiency and mechanism of tetracycline adsorption by EPS from strain J1 were studied. Adsorption efficiency was evaluated at different conditions. Results showed that optimal adsorption efficiency was 71.68 % with 60 mg L-1 of EPS from strain J1 and 90 MUL of 10 % (w/v) CaCl2 in 100 mL of tetracycline solution (80 MUg L-1) with pH of 8.0. Experimental data was fitted well with Langmuir, Freundlich isotherm, and pseudo-second-order models. Analyses of E value, Ea value, thermodynamics, zeta potential variation, and Fourier transform infrared spectroscopy (FTIR) spectra proved that chemisorption was the main adsorption type and bridging was the main adsorption mechanism. Thermodynamic analysis indicated that adsorptive reaction was exothermic from 20 to 40 degrees C. In addition, humic acid (HA) showed little effect on the tetracycline adsorption by MFX. PMID- 27677998 TI - An ultrasound-assisted procedure for fast screening of mobile fractions of Cd, Pb and Ni in soil. Insight into method optimization and validation. AB - A fast ultrasound-assisted sequential extraction (UASE) procedure for the determination of cadmium, lead and nickel fractions in soil was developed and fully validated. The working parameters of an ultrasound probe were optimized by comparing the content of metals in soil extracts obtained by the UASE procedure with that obtained by the conventional (with the aid of a vertical rotor) modified Community Bureau of Reference (BCR) procedure. The content of metals in soil fractions was determined by electrothermal atomic absorption spectrometry. The total time of extraction of metals from soil was shorten from 48 h to 27 min (total sonication time). The trueness of the developed method was confirmed by analysis of the certified reference material BCR-701. In order to indicate critical points of the developed UASE method, uncertainties of fractionation results were calculated and compared with those calculated for conventional modified BCR procedure. The method usefulness was tested for the determination of metal fractions in different types of soil collected in the Podlasie Province (Poland). The proposed procedure could be used for fast screening of mobile fractions of several heavy metals in soil. PMID- 27677999 TI - Alternative dry separation of PM10 from soils for characterization by kinetic extraction: example of new Caledonian mining soils. AB - A simple new device for dry separation of fine particulate matter from bulk soil samples is presented here. It consists of a stainless steel tube along which a nitrogen flow is imposed, resulting in the displacement of particles. Taking into account particle transport, fluid mechanics, and soil sample composition, a tube 6-m long, with a 0.04-m diameter, was found best adapted for PM10 separation. The device rapidly produced several milligrams of particulate matter, on which chemical extractions with EDTA were subsequently performed to study the kinetic parameters of extractable metals. New Caledonian mining soils were chosen here, as a case-study. Although the easily extracted metal pool represents only 0.5-6.4 % of the total metal content for the elements studied (Ni, Co, Mn), the total concentrations are extremely high. This pool is therefore far from negligible, and can be troublesome in the environment. This dry technique for fine particle separation from bulk parent soil eliminates the metal-leaching risks inherent in wet filtration and should therefore ensure safe assessment of environmental quality in fine-textured, metal-contaminated soils. PMID- 27678002 TI - Ankylosis of the temporomandibular joint secondary to neonatal group B streptococcal sepsis. PMID- 27678000 TI - Integrated bioleaching of copper metal from waste printed circuit board-a comprehensive review of approaches and challenges. AB - Waste electrical and electronic equipment (e-waste) is the most rapidly growing waste stream in the world, and the majority of the residues are openly disposed of in developing countries. Waste printed circuit boards (WPCBs) make up the major portion of e-waste, and their informal recycling can cause environmental pollution and health risks. Furthermore, the conventional disposal and recycling techniques-mechanical treatments used to recover valuable metals, including copper-are not sustainable in the long term. Chemical leaching is rapid and efficient but causes secondary pollution. Bioleaching is a promising approach, eco-friendly and economically feasible, but it is slower process. This review considers the recycling potential of microbes and suggests an integrated bioleaching approach for Cu extraction and recovery from WPCBs. The proposed recycling system should be more effective, efficient and both technically and economically feasible. PMID- 27678001 TI - Military and veteran health behavior research and practice: challenges and opportunities. AB - There are 2.1 million current military servicemembers and 21 million living veterans in the United States. Although they were healthier upon entering military service compared to the general U.S. population, in the longer term veterans tend to be of equivalent or worse health than civilians. One primary explanation for the veterans' health disparity is poorer health behaviors during or after military service, especially areas of physical activity, nutrition, tobacco, and alcohol. In response, the Department of Defense and Department of Veterans Affairs continue to develop, evaluate, and improve health promotion programs and healthcare services for military and veteran health behavior in an integrated approach. Future research and practice is needed to better understand and promote positive health behavior during key transition periods in the military and veteran life course. Also paramount is implementation and evaluation of existing interventions, programs, and policies across the population using an integrated and person centered approach. PMID- 27678003 TI - Adenylyl cyclase 3 haploinsufficiency confers susceptibility to diet-induced obesity and insulin resistance in mice. AB - Adenylyl cyclase 3 (Adcy3), a member of the mammalian adenylyl cyclase family responsible for generating the second messenger cAMP, has long been known to play an essential role in olfactory signal transduction. Here, we demonstrated that Adcy3 heterozygous null mice displayed increased visceral adiposity in the absence of hyperphagia and developed abnormal metabolic features characterized by impaired insulin sensitivity, dyslipidemia, and increased plasma levels of proinflammatory cytokines on both chow and high-fat diet (HFD). Of note, HFD decreased the Adcy3 expression in white adipose tissue, liver, and muscle. We also report for the first time that Adcy3 haploinsufficiency resulted in reduced expression of genes involved in thermogenesis, fatty acid oxidation, and insulin signaling, with enhanced expression of genes related to adipogenesis in peripheral tissues of mice. In conclusion, these findings suggest that cAMP signals generated by Adcy3 in peripheral tissues may play a pivotal role in modulating obesity and insulin sensitivity. PMID- 27678005 TI - The influence of fiscal rules on healthcare policy in the United States and the Netherlands. AB - Governments use fiscal rules to put a framework and limits on how budgetary challenges are addressed, but the rules themselves are still an understudied area among health policy scholars. For a long time, healthcare held a somewhat separate status because of the reliance on entitlements and dedicated revenue streams. However, the combined forces of advocates for integral decision-making, central budget control and the increasing costs might shift healthcare towards budgetary frameworks that currently apply to other spending categories. In this paper, we study fiscal rules that the US and the Netherlands have adopted since 2010 and their impact on healthcare policy. Our analysis shows that fiscal rules can have an impact on the rationing of healthcare. In the studied timeframe, the rules seem to have more impact on budget outcomes than on the budget process itself. In addition, the convergence of fiscal and program policy objectives seems to be better accomplished in a budgetary system that applies enforceable budget ceilings. Budgeting for health entitlements requires a comprehensive and tailor-made approach and the composition of traditional rules might not fully answer to the complexities of healthcare policy. This paper aims to contribute to that debate and the way we think about healthcare budgeting. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27678004 TI - Helical model of smooth muscle myosin filament and the ribbons made of caldesmon: history revisited. AB - In early studies on smooth muscle, I described a crude myosin fraction (CMF) in which self-assembly of myosin filaments was observed. For the first time, the 14 nm periodicity stemming from regular arrangement of myosin heads on the filament surface was observed (Sobieszek in J Mol Biol 70:741-744, 1972). In this fraction, we also observed formation of long ribbon-shaped aggregates exhibiting a 5.6-nm periodicity, characteristic of tropomyosin (TM) paracrystals (Sobieszek and Small in Phil Trans R Soc Lond B 265:203-212, 1973). We therefore concluded that these ribbons were made of TM and they might be related to the myosin ribbons observed in electron micrographs (EM) of intact smooth muscle (Lowy and Small in Nature 227:46-51, 1970; Small and Squire in Mol Biol 67:117-149, 1972). Subsequently, Small (J Cell Sci 24:327-349, 1977) concluded that the ribbons observed in the EM sections were an artifact, but their observation in the CMF was not addressed. I have now revisited two aspects of the above studies. Firstly, based on my new multi-angle laser-scattering data and considering the length and stability of the building unit for the filament, a myosin trimer fit better to the previously proposed helical structure. Secondly, after two decades of systematic examinations of protein compositions in multiple smooth muscle extracts and isolated filaments, I concluded that the ribbons were made of caldesmon and not TM. Thirdly, actin-activated ATPase activity measurements indicated that modulation of this activity (by CaD and TM) was synergistic, cooperative and depended on myosin to actin ratio. PMID- 27678006 TI - Children with ADHD symptoms show decreased activity in ventral striatum during the anticipation of reward, irrespective of ADHD diagnosis. AB - BACKGROUND: Changes in reward processing are thought to be involved in the etiology of attention-deficit/hyperactivity disorder (ADHD), as well as other developmental disorders. In addition, different forms of therapy for ADHD rely on reinforcement principles. As such, improved understanding of reward processing in ADHD could eventually lead to more effective treatment options. However, differences in reward processing may not be specific to ADHD, but may be a trans diagnostic feature of disorders that involve ADHD-like symptoms. METHODS: In this event-related fMRI study, we used a child-friendly version of the monetary incentive delay task to assess performance and brain activity during reward anticipation. Also, we collected questionnaire data to assess reward sensitivity in daily life. For final analyses, data were available for 27 typically developing children, 24 children with ADHD, and 25 children with an autism spectrum disorder (ASD) and ADHD symptoms. RESULTS: We found decreased activity in ventral striatum during anticipation of reward in children with ADHD symptoms, both for children with ADHD as their primary diagnosis and in children with autism spectrum disorder and ADHD symptoms. We found that higher parent-rated sensitivity to reward was associated with greater anticipatory activity in ventral striatum for children with ADHD symptoms. In contrast, there was no relationship between the degree of ADHD symptoms and activity in ventral striatum. CONCLUSIONS: We provide evidence of biological and behavioral differences in reward sensitivity in children with ADHD symptoms, regardless of their primary diagnosis. Ultimately, a dimensional brain-behavior model of reward sensitivity in children with symptoms of ADHD may be useful to refine treatment options dependent on reward processing. PMID- 27678007 TI - Enteric co-innervation of striated muscle in the esophagus: still enigmatic? AB - The existence of a distinct ganglionated myenteric plexus between the two layers of the striated tunica muscularis of the mammalian esophagus has represented an enigma for quite a while. Although an enteric co-innervation of vagally innervated motor endplates in the esophagus has been suggested repeatedly, it was not possible until recently to demonstrate this dual innervation. Twenty-two years ago, we were able to demonstrate that motor endplates in the rat esophagus receive dual innervation from both vagal nerve fibers originating in the brain stem and from varicose enteric nerve fibers originating in the myenteric plexus. Meanwhile, a considerable amount of data has been gathered on enteric co innervation and its occurrence in the esophagus of a variety of species including humans, its neurochemistry, spatial relationships on motor endplates, ontogeny and possible functional roles. These data underline the significance of this newly discovered innervation component, although its function in vivo is still largely unknown. The aim of this review, which is an update of our previous paper (Worl and Neuhuber in Histochem Cell Biol 123(2):117-130. doi: 10.1007/s00418-005 0764-7 , 2005a), is to summarize the current knowledge about enteric co innervation of esophageal striated muscle and to provide some hints as to its functional significance. PMID- 27678008 TI - Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04). Among treated patients, 39 relapsed during the follow-up period. These patients were characterized before treatment by a higher incidence of trisomy 12 (38 vs 11%, P < .001) and TP53 disruption (31 vs 4%, P = .0002). A significantly shorter 5-year overall survival was found for treated patients with CK (72.4 vs 85.8%; P = .007), unmutated IGHV (70 vs 100%; P = .04), or TP53 disruption (55.7 vs 82.7%; P < .0001). Three risk groups were defined based on the status of TP53 disruption or unmutated IGVH, which differed significantly in terms of 5-year overall survival. Moreover, the presence of CK impacted pejoratively 5-year overall survival and progression-free survival in all these 3 groups. Conventional karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required. PMID- 27678009 TI - Expression pattern and phenotypic characterization of the mutant strain reveals target genes and processes regulated by pka1 in the dimorphic fission yeast Schizosaccharomyces japonicus. AB - The cAMP cascade plays an important role in several biological processes. Thus, study of its molecular details can contribute to a better understanding of these processes, treatment of diseases, or even finding antifungal drug targets. To gain further information about the PKA pathway, and its evolutionarily conserved and species-specific features, the central regulator pka1 gene, which encodes the cAMP-dependent protein kinase catalytic subunit, was studied in the less known haplontic, dimorphic fission yeast Schizosaccharomyces japonicus. Namely, this species belongs to a highly divergent phylogenetic branch of fungi. Furthermore, S. japonicus had only a single copy pka1 gene in contrast to the budding yeasts. Therefore, the pka1 deleted mutant was created, whose RNA sequencing and phenotypic studies revealed that the Pka1 regulated at least 373 genes, among them further kinases, phosphatases and transcriptional regulators. It regulated elongation of hyphae, cell size, aging and stress response. Furthermore, half of the pka1 target genes seemed to be conserved in Schizosaccharomyces pombe and S. japonicus. However, there were oppositely regulated genes in the two closely related species. The target genes suggest that this single gene must be able to fulfill all the functions of TPK1-3 of Saccharomyces cerevisiae. Thus, our results shed light on certain similarities and differences of the PKA pathway of S. japonicus compared to the budding yeasts and confirmed the multifunctionality of the pka1 gene, but further experiments are needed to prove its involvement in the metabolic processes and transport. PMID- 27678010 TI - New quality assurance program integrating "modern radiotherapy" within the German Hodgkin Study Group. AB - INTRODUCTION: Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin's lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). METHODS: In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. RESULTS: The expert panel developed guidelines and criteria to analyse "modern" field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). CONCLUSION: To develop a QAP of "modern RT", the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups. PMID- 27678011 TI - The Role of Language Skill in Child Psychopathology: Implications for Intervention in the Early Years. AB - In this narrative review, we suggest that children's language skill should be targeted in clinical interventions for children with emotional and behavioral difficulties in the preschool years. We propose that language skill predicts childhood emotional and behavioral problems and this relationship may be mediated by children's self-regulation and emotion understanding skills. In the first sections, we review recent high-quality longitudinal studies which together demonstrate that that children's early language skill predicts: (1) emotional and behavioral problems, and this relationship is stronger than the reverse pattern; (2) self-regulation skill; this pattern may be stronger than the reverse pattern but moderated by child age. Findings also suggest that self-regulation skill mediates the relation between early language skill and children's emotional and behavioral problems. There is insufficient evidence regarding the mediating role of emotion understanding. In subsequent sections, we review evidence demonstrating that: (1) particular kinds of developmentally targeted parent-child conversations play a vital role in the development of language skill, and (2) some current clinical interventions, directly or indirectly, have a beneficial impact on children's vocabulary and narrative skills, but most approaches are ad hoc. Targeting language via parent-child conversation has the potential to improve the outcomes of current clinical interventions in the preschool years. PMID- 27678012 TI - Heteroatom Tuning of Bimolecular Criegee Reactions and Its Implications. AB - High-level quantum-chemical calculations have been performed to understand the key reactivity determinants of bimolecular reactions of Criegee intermediates and H2 X (X=O, S, Se, and Te). Criegee intermediates are implicated as key intermediates in atmospheric, synthetic organic, and enzymatic chemistry. Generally, it is believed that the nature and location of substituents at the carbon of the Criegee intermediate play a key role in determing the reactivity. However, the present work suggests that it is not only the substitution of the Criegee intermediate, but the nature of the heteroatom in H2 X that also plays a crucial role in determining the reactivity of the interaction between the Criegee intermediate and H2 X. The barriers for the reactions of Criegee intermediates and H2 X satisfy an inverse correlation with the bond strength of X-H in H2 X, and a direct correlation with the first pKa of H2 X. This heteroatom tuning causes a substantial barrier lowering of 8-11 kcal mol-1 in the Criegee reaction barrier in going from H2 O to H2 Te. An important implication of these results is that the reaction of the Criegee intermediate and H2 S could be a source of thioaldehydes, which are important in plantery atmospheres and synthetic organic chemistry. By performing the reaction of Criegee intermediates and H2 S under water or acid catalysis, thioladehydes could be detected in a hydrogen-bonded complexed state, which is significantly more stable than their uncomplexed form. As a result, simpler aliphatic thioaldehydes could be selectively synthesized in the laboratory, which, otherwise, has been a significant synthetic challenge because of their ability to oligomerize. PMID- 27678014 TI - Electric Eel-Skin-Inspired Mechanically Durable and Super-Stretchable Nanogenerator for Deformable Power Source and Fully Autonomous Conformable Electronic-Skin Applications. AB - Electric eel-skin-inspired mechanically durable and super-stretchable nanogenerator is demonstrated for the first time by using triboelectric effect. This newly designed nanogenerator can produce electricity by touch or tapping despite under various extreme mechanical deformations or even after experiencing damage. This device can be used not only as deformable and wearable power source but also as fully autonomous and self-sufficient adaptive electronic skin system. PMID- 27678013 TI - Xenograft of microencapsulated Sertoli cells restores glucose homeostasis in db/db mice with spontaneous diabetes mellitus. AB - BACKGROUND: Increased abdominal fat and chronic inflammation in the expanded adipose tissue of obesity contribute to the development of insulin resistance and type 2 diabetes mellitus (T2D). The emerging immunoregulatory and anti inflammatory properties of Sertoli cells have prompted their application to experimental models of autoimmune/inflammatory disorders, including diabetes. The main goal of this work was to verify whether transplantation of microencapsulated prepubertal porcine Sertoli cells (MC-SC) in the subcutaneous abdominal fat depot of spontaneously diabetic and obese db/db mice (homozygous for the diabetes spontaneous mutation [Leprdb ]) would: (i) improve glucose homeostasis and (ii) modulate local and systemic immune response and adipokines profiles. METHODS: Porcine prepubertal Sertoli cells were isolated, according to previously established methods and enveloped in Barium alginate microcapsules by a mono air jet device. MC-SC were then injected in the subcutaneous abdominal fat depot of db/db mice. RESULTS: We have preliminarily shown that graft of MC-SC restored glucose homeostasis, with normalization of glycated hemoglobin values with improvement of the intraperitoneal glucose tolerance test in 60% of the treated animals. These results were associated with consistent increase, in the adipose tissue, of uncoupling protein 1 expression, regulatory B cells, anti-inflammatory macrophages and a concomitant decrease of proinflammatory macrophages. Furthermore, the treated animals showed a reduction in inducible NOS and proinflammatory molecules and a significant increase in an anti-inflammatory cytokine such as IL-10 along with concomitant rise of circulating adiponectin levels. The anti-hyperglycemic graft effects also emerged from an increased expression of GLUT-4, in conjunction with downregulation of GLUT-2, in skeletal muscle and liver, respectively. CONCLUSIONS: Preliminarily, xenograft of MC-SC holds promises for an effective cell therapy approach for treatment of experimental T2D. PMID- 27678015 TI - Colon Obstruction as an Isolated Late Gastrointestinal Metastasis of Testicular Seminoma. PMID- 27678016 TI - Prevalence and molecular characterization of human rhinovirus in stool samples of individuals with and without acute gastroenteritis. AB - Human rhinovirus (RV) most often causes mild upper respiratory tract infection. Although RV is routinely isolated from the respiratory tract, few studies have examined RV in other types of clinical samples. The prevalence of RV was examined in 1,294 stool samples collected mostly from children with acute gastroenteritis residing in Bangkok and Khon Kaen province of Thailand between January 2010 and October 2014. In addition, 591 samples from hand-foot-mouth disease (HFMD) or herpangina patients who do not have gastroenteritis served as a comparison group. Samples were initially screened by semi-nested PCR for the RV 5'UTR through the VP2 capsid region. RV genotyping and phylogenetic analysis were performed on the VP4/VP2 regions. Among children with acute gastroenteritis, RV was found in 2.3% (30/1,294) of stool samples, which comprised 47% (14/30) RV-A, 17% (5/30) RV-B, and 37% (11/30) RV-C. In the comparison group, 0.8% (5/591) was RV-positive and RV-C (3/5) was the major species found. Interestingly, RV was recovered more often from children with acute gastroenteritis than from those with HFMD or herpangina. As many as 31 RV types were present in the gastroenteritis stools, which were different than the types found in those with HFMD or herpangina. J. Med. Virol. 89:801-808, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27678017 TI - The challenge of integrating proximate and ultimate causes to reconstruct the natural histories of venoms: the evolutionary link. PMID- 27678018 TI - The interaction effect of attentional bias and attentional control on dispositional anxiety among adolescents. AB - Research has shown that children and adolescents with attentional control deficits tend to have high anxiety and exhibit threat-related selective attentional bias. This study aimed to investigate how positive and negative attentional biases would interact with attentional control on dispositional anxiety. One hundred and twenty participants aged 18 years of age or younger participated in a visual dot-probe task to measure their attentional bias and completed psychological questionnaires to measure their trait anxiety, and attentional control. Mean reaction times to the probe in milliseconds were used to measure attentional bias. Overall, our participants showed a bigger tendency towards attending to positive emotional stimuli than to negative emotional stimuli. Adolescents with high dispositional anxiety showed poorer attentional control. Regression analyses showed that attentional control interact with negative attentional bias to affect anxiety. For participants with high attentional control, higher negative attentional bias was associated with lower trait anxiety. Trait anxiety was not related to negative attentional bias for participants with low attentional control. Positive attentional bias showed no significant relationship with dispositional anxiety, either alone or in interaction with attentional control. Theoretical and clinical implications of the findings are also discussed. PMID- 27678019 TI - Abstracts from the 20th Annual Meeting of the European Council for Cardiovascular Research (ECCR), Poiano, Lake Garda, 14-16 October 2016. PMID- 27678021 TI - GMC closes inquiry into troubled Aberdeen hospital. PMID- 27678020 TI - Bending rules: the shape of the perceptual generalisation gradient is sensitive to inference rules. AB - Generalising what is learned about one stimulus to other but perceptually related stimuli is a basic behavioural phenomenon. We evaluated whether a rule learning mechanism may serve to explain such generalisation. To this end, we assessed whether inference rules communicated through verbal instructions affect generalisation. Expectancy ratings, but not valence ratings, proved sensitive to this manipulation. In addition to revealing a role for inference rules in generalisation, our study has clinical implications as well. More specifically, we argue that targeting inference rules might prove to be an effective strategy to affect the excessive generalisation that is often observed in psychopathology. PMID- 27678022 TI - Clinical and Molecular Characterization of Community-Onset Urinary Tract Infections Due to Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae. AB - OBJECTIVE To evaluate risk factors for and molecular characteristics of community onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) urinary tract infections (UTIs) in a US health system. DESIGN Case-control study. PARTICIPANTS All patients presenting to the emergency department or outpatient practices with EB UTIs from December 21, 2010, through April 22, 2013, were included. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched 1:1 on study year. METHODS Risk factors for ESC-R EB UTI were assessed using multivariable conditional logistic regression. A subset of case isolates was evaluated for extended-spectrum beta-lactamases. RESULTS A total of 302 patients with community-onset EB UTI were included, of which 151 were cases. On multivariable analysis, risk factors for ESC-R EB UTI included trimethoprim-sulfamethoxazole use in the prior 6 months (odds ratio, 2.40 [95% CI, 1.22-4.70]; P=.01), older age (1.03 [1.01-1.04]; P<.001), diabetes (2.91 [1.32-6.41]; P=.008), and presentation to the emergency department ( 2.42 [1.31 4.46]; P=.005). The prevalence of extended-spectrum beta-lactamases among 120 case isolates was 52% CTX-M, 29% TEM, 20% OXA, and 13% SHV. The prevalence of AmpC was 25%. Pulsed-field gel electrophoresis of the CTX-M Escherichia coli isolates showed no distinct clusters. CONCLUSIONS Use of trimethoprim sulfamethoxazole, older age, diabetes, and presentation to the emergency department were associated with community-onset ESC-R EB UTI. There was a high prevalence of CTX-M among our community isolates. Further studies are needed to determine strategies to limit emergence of these organisms in the community. Infect Control Hosp Epidemiol 2016;1433-1439. PMID- 27678023 TI - The significance of FOXP1 in diffuse large B-cell lymphoma. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of mature B-cell lymphoma. While the majority of patients are cured with immunochemotherapy incorporating the anti-CD20 monoclonal antibody rituximab (R-CHOP), relapsed and refractory patients still have a dismal prognosis. DLBCL subtypes including an aggressive activated B-cell-like (ABC) and a more favorable prognosis germinal center-like (GCB) DLBCL have been identified by gene expression profiling and are characterized by distinct genetic abnormalities and oncogenic pathways. This identification of novel molecular targets is now enabling clinical trials to evaluate more effective personalized approaches to DLBCL therapy. The forkhead transcription factor FOXP1 is highly expressed in the ABC-DLBCL gene signature and has been extensively studied within the context of DLBCL for more than a decade. Here, we review the significance of FOXP1 in the pathogenesis of DLBCL, summarizing data supporting its utility as a prognostic and subtyping marker, its targeting by genetic aberrations, the importance of specific isoforms, and emerging data demonstrating a functional role in lymphoma biology. FOXP1 is one of the critical transcription factors whose deregulated expression makes important contributions to DLBCL pathogenesis. Thus, FOXP1 warrants further study as a potential theranostic in ABC-DLBCL. PMID- 27678024 TI - Development and functional demonstration of a wireless intraoral inductive tongue computer interface for severely disabled persons. AB - PURPOSE: Individuals with tetraplegia depend on alternative interfaces in order to control computers and other electronic equipment. Current interfaces are often limited in the number of available control commands, and may compromise the social identity of an individual due to their undesirable appearance. The purpose of this study was to implement an alternative computer interface, which was fully embedded into the oral cavity and which provided multiple control commands. METHODS: The development of a wireless, intraoral, inductive tongue computer was described. The interface encompassed a 10-key keypad area and a mouse pad area. This system was embedded wirelessly into the oral cavity of the user. The functionality of the system was demonstrated in two tetraplegic individuals and two able-bodied individuals Results: The system was invisible during use and allowed the user to type on a computer using either the keypad area or the mouse pad. The maximal typing rate was 1.8 s for repetitively typing a correct character with the keypad area and 1.4 s for repetitively typing a correct character with the mouse pad area. CONCLUSION: The results suggest that this inductive tongue computer interface provides an esthetically acceptable and functionally efficient environmental control for a severely disabled user. Implications for Rehabilitation New Design, Implementation and detection methods for intra oral assistive devices. Demonstration of wireless, powering and encapsulation techniques suitable for intra oral embedment of assistive devices. Demonstration of the functionality of a rechargeable and fully embedded intra oral tongue controlled computer input device. PMID- 27678026 TI - Correction to: Bioprinting: an assessment based on manufacturing readiness levels. PMID- 27678025 TI - Emerging drugs to reduce abnormal beta-amyloid protein in Alzheimer's disease patients. AB - INTRODUCTION: Currently available drugs against Alzheimer's disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process. Putative disease-modifying drugs are in development and target beta-amyloid (Abeta) peptide and tau protein, the principal neurophatological hallmarks of the disease. Areas covered: Phase III clinical studies of emerging anti-Abeta drugs for the treatment of AD were searched in US and EU clinical trial registries and in the medical literature until May 2016. Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the beta secretase cleaving enzyme (BACE) (verubecestat), three anti-Abeta monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1). These drugs are mainly being tested in subjects during early phases of AD or in subjects at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The hope is to intervene in the disease process when it is not too late. However, previous clinical failures with anti-Abeta drugs and the lack of fully understanding of the pathophysiological role of Abeta in the development of AD, put the new drugs at substantial risk of failure. PMID- 27678027 TI - Recombinant scFv antibodies against infectious pancreatic necrosis virus isolated by flow cytometry. AB - Infectious pancreatic necrosis is a significant disease of farmed salmonids in China. In this study, a single chain variable fragment (scFv) antibody library derived from rainbow trout (Oncorhynchus mykiss) and viral protein VP2 of a Chinese infectious pancreatic necrosis virus (IPNV) isolate ChRtm213 were co expressed by a bacterial display technology. The library was subjected to three rounds of screening by flow cytometry (FCM) to select IPNV specific antibodies. Six antibody clones with different mean fluorescence intensities (MFI) were obtained by picking colonies at random. The antibody clones were expressed and purified. The purified IPNV-specific scFv antibodies were used successfully in Western blotting, enzyme linked immunosorbent assay (ELISA) and an immunofluorescence antibody test (IFAT). This method provides a high throughput means to screen an antibody library by flow cytometry, and isolate a panel of antibody that can be used as potential reagents for the detection and study of IPNV that are prevalent in China. PMID- 27678028 TI - A sensitive virus yield assay for evaluation of Antivirals against Zika Virus. AB - Despite the rapid spread of Zika virus (ZIKV) infection and associated neurological complications in the America's, prophylactic or therapeutic countermeasures are not currently available. This is mostly due to the fact that until recently there was no presumed need for medical intervention since there was no association between ZIKV infection and significant human morbidity. Consequently, there are currently no tools due mostly to the lack of sensitive cell based assays amenable for identification of ZIKV inhibitors. To address this unmet need we have developed a cell based virus yield assay suitable for testing antivirals against Zika virus. Using bioinformatics, several isolates of ZIKV from the Americas, Africa, and Asia were analyzed for sequence similarity. The alignment data were then used to design primers targeting a ZIKV genomic region that was highly conserved among all the ZIKV isolates. Subsequently, primers were used in a sensitive, quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay to detect ZIKV RNA. The qRT-PCR assay was found to be highly sensitive (lower limit of detection between-10-100 copies) and reproducible. Evaluation of the primers and probes used for ZIKV against another flavivirus (Dengue virus) demonstrated specificity of detection. To evaluate potential of qRT-PCR assay as an antiviral screening tool against ZIKV, Vero cells pretreated with Type I Interferons (IFN alpha) were infected with virus, followed by measurement of ZIKV RNA found in the cell culture supernatants using qRT-PCR assay. Dose-dependent antiviral activity of Type I Interferons and mycophenolic acid (MPA) against Zika virus in this cell culture system was confirmed using qRT PCR. Due to reproducible assay performance, qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. PMID- 27678029 TI - Cross-border reproductive care: an Ethics Committee opinion. AB - Cross-border reproductive care (CBRC) is a growing worldwide phenomenon, raising questions about why assisted reproductive technology (ART) patients travel abroad, what harms and benefits may result, and what duties health-care providers may have in advising and treating patients who travel for reproductive services. Cross-border care offers benefits and poses harms to ART stakeholders, including patients, offspring, providers, gamete donors, gestational carriers, and local populations in destination countries. This document replaces the previous document of the same name, last published in 2013 (Fertil Steril 2013;100:645 50). PMID- 27678030 TI - Direct vitamin D3 actions on rhesus macaque follicles in three-dimensional culture: assessment of follicle survival, growth, steroid, and antimullerian hormone production. AB - OBJECTIVE: To investigate the direct actions of active 1,25-dihydroxy vitamin D3 (VD3) upon primate follicular development at specific stages of folliculogenesis. DESIGN: Secondary preantral follicles were isolated from rhesus monkeys ovaries, encapsulated in alginate, and cultured for 40 days. Follicles were randomly assigned to experimental groups of control, low-dose VD3 (LVD3; 25 pg/mL), and high-dose VD3 (HVD3; 100 pg/mL). SETTING: National primate research center. ANIMAL(S): Adult, female rhesus macaques (Macaca mulatta). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicle survival and growth, as well as oocyte size, were assessed. Progesterone (P4), androstenedione (A4), E2, and antimullerian hormone (AMH) concentrations in culture media were measured. RESULT(S): Compared with the control group, LVD3 increased preantral follicle survival at week 2 by >66%, while HVD3 increased antral follicle diameters at week 5. Follicles with diameters >=500 MUm at week 5 were categorized as fast-growing follicles. Higher percentages of fast-growing follicles were obtained after HVD3 treatment. Although P4, A4, and E2 production by antral follicles was not altered by VD3, AMH concentrations were 36% higher in the LVD3 group relative to controls at week 5. Oocytes with larger diameters were retrieved from antral follicles developed in both LVD3 and HVD3 groups compared with controls. CONCLUSION(S): The addition of LVD3 increased preantral follicle survival and maintained AMH production by antral follicles, while HVD3 improved antral follicle growth. VD3 supplement promoted oocyte growth in in vitro-developed follicles. Direct actions of VD3 on the primate follicle appear to be both dose and stage dependent. PMID- 27678031 TI - Obstetric and perinatal outcomes after either fresh or thawed frozen embryo transfer: an analysis of 112,432 singleton pregnancies recorded in the Human Fertilisation and Embryology Authority anonymized dataset. AB - OBJECTIVE: To explore obstetric and perinatal outcomes in singleton pregnancies occurring as a result of fresh and thawed frozen embryo transfer using anonymized Human Fertilisation and Embryology Authority data. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Singleton births after IVF/intracytoplasmic sperm injection cycles in the United Kingdom (1991-2011). INTERVENTION(S): A total of 112,432 cycles (95,911 fresh and 16,521 frozen) were analyzed using multivariate logistic regression to explore associations between type of embryo transferred (frozen vs. fresh) and obstetric and perinatal outcomes. Relative risks (RRs) and their 99.5% confidence intervals (CIs) were calculated using Stata 14 MP, adjusting for potential confounders. MAIN OUTCOME MEASURE(S): Birth weight. RESULT(S): The adjusted RR (99.5% CI) of low birth weight [0.73 (0.66-0.80)] and very low birth weight [0.78 (0.63-0.96)] were all lower after frozen embryo transfer; however, RR of having a high birth weight baby was higher [1.64 (1.53-1.76)]. There was no difference in RR of preterm birth [0.96 (0.88-1.03)], very preterm birth [0.86 (0.70-1.05)], and congenital anomalies [0.86 (0.73-1.01)]. CONCLUSION(S): The findings of low birth and very low birth weight after thawed frozen embryo transfer are consistent with the literature and provide reassurance regarding the outcome of pregnancies after frozen embryo transfers. However, they highlight the possibility of high birth weight in these babies. Because these results are based on observational data, further evidence from randomized, controlled trials is needed before elective cryopreservation of all embryos is practiced in preference to the current practice of transfer of fresh embryos. PMID- 27678032 TI - Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. AB - Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to identify who is at high risk, how to prevent OHSS, and the treatment for existing OHSS. PMID- 27678033 TI - Addition of neither recombinant nor urinary luteinizing hormone was associated with an improvement in the outcome of autologous in vitro fertilization/intracytoplasmatic sperm injection cycles under regular clinical settings: a multicenter observational analysis. AB - OBJECTIVE: To determine whether the addition of either urinary or recombinant LH in patients undergoing routine clinical care improved the outcome in terms of the number of oocytes recovered for insemination or the delivery rate per initiated cycle. DESIGN: Cohort analysis. PATIENT(S): Couples undergoing IVF/ICSI in 158 institutions in 15 countries in Latin America. SETTING: In vitro fertilization clinics. INTERVENTION(S): We compared the outcome of three different protocols of COH, including rFSH only, rFSH plus rLH, and rFSH plus hMG. MAIN OUTCOME MEASURE(S): The number of mature oocytes recovered and inseminated; proportion of ETs at the blastocyst stage; clinical pregnancy, miscarriage, and delivery rates; proportion of cycles with embryo cryopreservation; and mean number of embryos cryopreserved. RESULT(S): After correcting for the age of the female partner, body mass index, number of embryos transferred, and stage of embryo development at transfer, we found that LH addition was not associated with an increase in the mean number of metaphase II oocytes inseminated or with an increase in the delivery rate or changes in the miscarriage rate. CONCLUSION(S): Our study strongly suggests that in routine clinical practice, the type of controlled ovarian stimulation-FSH alone or in combination with LH-has little impact on the outcome of assisted reproductive technology; therefore a more friendly and accessible alternative should be favored. PMID- 27678034 TI - Which female cancer patients fail to receive fertility counseling before treatment in the state of Georgia? AB - OBJECTIVE: To assess which characteristics are associated with failure to receive fertility counseling among a cohort of young women diagnosed with cancer. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): A total of 1,282 cancer survivors, of whom 1,116 met the inclusion criteria for the analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The main outcome in this study was whether or not women reported receiving any information at the time of their cancer diagnosis on how cancer treatment might affect their ability to become pregnant. RESULT(S): Forty percent of cancer survivors reported that they did not receive fertility counseling at the time of cancer diagnosis. Women were more likely to fail to receive counseling if they had only a high school education or less or if they had given birth. Cancer-related variables that were associated with a lack of counseling included not receiving chemotherapy as part of treatment and diagnosis with certain cancer types. CONCLUSION(S): Counseling about the risk of infertility and available fertility preservation options is important to cancer patients. Additionally, counseling can make women aware of other adverse reproductive outcomes, such as early menopause and its associated symptoms. Less-educated women and parous women are at particular risk of not getting fertility-related information. Programs that focus on training not just the oncologist, but also other health care providers involved with cancer care, to provide fertility counseling may help to expand access. PMID- 27678035 TI - Hormonal contraception and thrombosis. AB - The safety of combined hormonal contraceptives (CHCs) has been documented by years of follow-up, and the occurrence of venous thromboembolism (VTE) possibly related to their use is rare in the young population exposed to these agents. The balance between the benefits and risks of contraceptive steroids is generally positive, in particular when compared with pregnancy's risks. Epidemiological studies led to different results showing either no difference in VTE risk between CHCs (active surveillance prospective studies) or an increase in risk (observational or database studies). The discrepancy may be explained by different study designs and the fact that important risk factors such as overweight, family history of thrombosis, and smoking were not adjusted for in some observational studies. To improve the safety of CHC, modifying the estrogen dose and type, selecting newer progestins, and alternative routes of delivery were implemented. Ethinyl- E2 (EE) exerts a stronger effect than E2 on estrogen dependent markers such as liver proteins and coagulation factors. To circumvent the metabolic changes induced by EE, more natural compounds such as E2 and E2 valerate (E2V) were developed, as well as new progestins structurally closer to P. Progestins when given alone do not increase VTE risk, and their risks and benefits depend upon their chemical structure, the type and dose of combined estrogen, and the delivery route. The lower impact of E2-based CHCs on metabolic markers may result in an improved safety profile. A recent study on clinical outcomes supports this hypothesis. In conclusion, CHCs remain a safe and effective choice to prevent unwanted pregnancy, and the risk of VTE is in general low. Careful consideration of individual risk factors should be given before prescribing to avoid cumulative risks and minimize the occurrence of unwanted events. PMID- 27678036 TI - Is elective single-embryo transfer a viable treatment policy in in vitro maturation cycles? AB - OBJECTIVE: To compare the clinical outcome of single-embryo transfer (SET) with double-embryo transfer (DET) in in vitro maturation (IVM) cycles performed in patients with polycystic ovary syndrome (PCOS), and to determine which factors predict those outcomes. DESIGN: A retrospective analysis. SETTING: Private assisted reproduction center. PATIENT(S): One hundred and fifty-nine women with PCOS. INTERVENTION(S): In vitro maturation with elective SET or DET conducted between September 2007 and May 2014. MAIN OUTCOME MEASURE(S): Live-birth rates. RESULT(S): Single-embryo transfer was performed in 83 patients (52.2%), and DET was performed in 76 patients (47.7%). When compared with the patients who had DET, the patients who had SET were statistically significantly younger (32.4 +/- 3.5 vs. 24.1 +/- 4.2 years) and had a shorter infertility duration (9.2 +/- 4.5 vs. 4.4 +/- 2.1 years), fewer previous ART cycles (<2 prior attempts, 39.5% vs. 6%; >=2 prior attempts, 60.5% vs. 0), fewer collected oocytes (15.1 +/- 4.6 vs. 12.6 +/- 3.8), fewer metaphase II oocytes (9.0 +/- 4.1 vs. 5.7 +/- 2.9), fewer fertilized oocytes (8.2 +/- 3.7 vs. 3.6 +/- 2.3), and a higher implantation rate (27% vs. 47%). The SET and DET groups had similar embryo quality and similar clinical pregnancy (44.6% vs. 44.7%) and live-birth rates (34.9% vs. 34.2%). Twin pregnancy rates were statistically significantly higher in the DET compared with the SET groups (9.2% vs. 2.4%). CONCLUSION(S): In vitro maturation is a successful assisted reproduction technique that can be an alternative to conventional in vitro fertilization in women presenting with PCOS-related infertility. Our observations suggest that SET is a feasible option to prevent multiple pregnancies while maintaining the live-birth rate. PMID- 27678038 TI - Using the Wharton-Sheares-George method to create a neovagina in patients with Mayer-Rokitansky-Kuster-Hauser syndrome: a step-by-step video tutorial. AB - OBJECTIVE: To provide a review of the literature regarding this technique as well as a step-by-step description with the goal of increasing its use as a safe surgical option. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by vaginal agenesis and a variety of mullerian duct anomalies. To date, a variety of procedures have been described for creating a neovagina, but the best treatment remains debated. The Wharton-Sheares-George method, a minimally invasive surgical approach for the creation of a neovagina, is remarkably simple to perform. DESIGN: Surgical video tutorial. SETTING: University hospital and referral center for pediatric and adolescent gynecology. PATIENT(S): A 20-year old woman with MRKH syndrome who underwent Wharton-Sheares-George neovaginoplasty. INTERVENTION(S): With the Wharton-Sheares-George neovaginoplasty the rudimentary mullerian ducts are dilated incrementally by pushing Hegar dilators in the direction of the pelvic axis, and the resulting median raphe is then intersected using diathermy. Subsequently a vaginal mold is inserted into the newly created cavity and held in position by two sutures. MAIN OUTCOME MEASURE(S): Discussion of the surgical steps according to the Wharton-Sheares George method and review of the anatomic and functional results. RESULTS: Reviewing the existing literature shows that a mean vaginal length and width of 8.3 and 3.3 cm, respectively, can be achieved, and so far no major intraoperative or postoperative complications or prolapse of the neovagina has been reported. Patients can achieve a high degree of general well-being as well as sexual and psychosocial functioning. However, as with most other methods, the presented method requires diligent patient compliance due to the lifelong need to actively avoid contraction of the neovagina. Also, as revealed by vaginal cultures and biopsies, the neovaginas remarkably resemble natural vaginas with regard to type of bacterial colonization and structure of epithelium. The process of spontaneous epithelialization of the neovagina is not fully understood, but has been observed to begin at the vaginal orifice and take several months to reach the apex. This leads to the assumption that the nonkeratinizing, stratified squamous epithelium originates from the preexisting vaginal epithelium of the vaginal dimple and migrates in a cranial direction. Alternatively, epithelialization might arise from pluripotent stem cells located in the obliterated mullerian ducts. CONCLUSION(S): The creation of a neovagina using the Wharton-Sheares-George method does not require allogenic or autologous transplants, nor does it require traction devices or specialized surgical equipment. Furthermore, the procedure is comparatively simple to perform and easy to learn. By following our step-by-step description of this technique, surgeons can offer a minimally invasive, quick, and safe surgical option that provides long-term results that are both functionally and anatomically satisfying. We believe that this technique represents a valuable alternative for the creation of a neovagina in patients with MRKH syndrome and thus should be investigated on a broader scale in the future. PMID- 27678039 TI - Ovarian hyperstimulation: past, present, and future. AB - The good physician treats the disease; the great physician treats the patient who has the disease. -William Osler. PMID- 27678037 TI - Male contraception. AB - Although female contraceptives are very effective at preventing unintended pregnancy, some women can not use them because of health conditions or side effects, leaving some couples without effective contraceptive options. In addition, many men wish to take active responsibility for family planning. Thus, there is a great need for male contraceptives to prevent unintended pregnancies, of which 80-90 million occur annually. At present, effective male contraceptive options are condoms and vasectomy, which are not ideal for all men. Therefore, efforts are under way to develop novel male contraceptives. This paper briefly reviews the advantages and disadvantages of condoms and vasectomies and then discusses the research directed toward development of novel methods of male contraception. PMID- 27678040 TI - Reproductive outcomes of familial oocyte donation. AB - OBJECTIVE: Oocyte donation (OD) from a family member may be more available to patients. Our objective was to compare reproductive outcomes of familial OD with those of unrelated OD. DESIGN: Retrospective cohort study in a single university affiliated center. SETTING: Not applicable. PATIENT(S): Four hundred thirty OD cycles performed from 2010 to 2014: 124 from family members and 306 from unrelated donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian stimulation parameters and cycle outcomes (total gonadotropin dose, number of retrieved oocytes, number of embryos, number of vitrified embryos, blastocyst transfer rate, rate of fresh transfers); endometrial preparation parameters; implantation, clinical pregnancy, miscarriage, and live birth rates; perinatal outcomes (gestational age at birth, birth weight, delivery mode, cesarean delivery rates). RESULT(S): Implantation, clinical pregnancy, miscarriage, and live birth rates were similar between familial OD cycles and unrelated OD cycles (32.9% vs. 39.7%, 41.9% vs. 44.4%, 30.7% vs. 30.9%, and 29% vs. 28.7%, respectively). Gestational age at birth and birth weight were similar (37.8 wk +/ 2.2 d vs. 37.1 wk +/- 3 d and 3,043 +/- 722 g vs. 2,906 +/- 788 g, respectively). Similar outcomes were also found in single-embryo transfer OD cycles (live birth rate 26.7% vs. 24.2%). Sister-to-sister OD cycles outcomes were similar to those of unrelated donors. CONCLUSION(S): The reproductive outcomes of familial OD are similar to those of unrelated OD. These findings are in contrast to previous presumptions regarding the efficiency of familial OD and may help in the counseling of women who need OD. PMID- 27678041 TI - Medication use and survival in diabetic patients with kidney cancer: A population based cohort study. AB - Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer. Receipt of metformin, statins or NSAIDs was defined using prescription claims. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. We used multivariable Cox proportional hazard regression, with medication use modeled with time-varying and cumulative exposure analyses to account for intermittent use. During the 14-year study period, we studied 613 patients. Current statin use was associated with a markedly reduced risk of death from any cause (adjusted hazard ratio 0.74; 95% CI 0.59-0.91) and death due to kidney cancer (adjusted hazard ratio 0.71; 95% CI 0.51-0.97). However, survival was not associated with current use of metformin or NSAIDs, or cumulative exposure to any of the medications studied. Among diabetic patients with kidney cancer, survival outcomes are associated with active statin use, rather than total cumulative use. These findings support the use of randomized trials to confirm whether diabetics with kidney cancer should be started on a statin at the time of cancer diagnosis to improve survival outcomes. PMID- 27678042 TI - Calycosin suppresses expression of pro-inflammatory cytokines via the activation of p62/Nrf2-linked heme oxygenase 1 in rheumatoid arthritis synovial fibroblasts. AB - The activation of synovial fibroblasts (SFs) and the subsequent production and expression of pro-inflammatory cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). In the current study, rheumatoid arthritis synovial fibroblasts (RASFs) isolated from the joint of the patients were used to evaluate the suppressive effects of calycosin (CAL), a compound derived from the Chinese medicinal herb Radix Astragali, on the expression of pro inflammatory cytokines in RASFs. The results demonstrated that increased mRNA expression levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-25 (IL-25), interleukin-33(IL-33) were significantly inhibited by CAL. Furthermore, the compound obviously suppressed IL 6 and IL-33 secretion. The key inflammatory mediator, cyclooxygenase-2 (COX-2) was significantly attenuated by CAL. A mechanistic study showed that the antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone 1(NQO1) and Nrf2 of RASFs were markedly activated by CAL. Furthermore, CAL potentiated the accumulation of sequestosome 1 (SQSTM1, p62) and the degradation of Kelch-like ECH-associated protein 1 (Keap1), thereby inducing Nrf2 translocation from the cytoplasm to the nucleus. Thus, CAL suppresses the expression of pro-inflammatory cytokines via p62/Nrf2-linked HO-1 induction in RASFs, which suggests that the compound should be further investigated as a candidate anti-inflammatory and anti-arthritic agent. PMID- 27678043 TI - Maternal depression research: socioeconomic analysis and density-equalizing mapping of the global research architecture. AB - Maternal depression can be accounted for one of the most common complications during pregnancy and the postpartum period affecting women all over the world. So far, no detailed map of the worldwide maternal depression research architecture has been constructed, which encompasses aspects of research activity, quality, and also socioeconomic features. Using the NewQIS platform, density-equalizing mapping projections, scientometric techniques, and economic benchmarking procedures were applied to evaluate global maternal depression research for the period between 1900 and 2012. In total, 7330 related publications and 3335 international collaborations were identified. The USA was the most active country concerning collaborations and total research activity. In the socioeconomic analysis of research activity in high-income countries, Australia was ranked first with an average of 412.05 maternal depression-related publications per 1000 billion US$ GDP (Q1), followed by the UK (Q1 = 373.51) and Canada (Q1 = 306.32). The group of upper-middle-income countries was led by South Africa (Q1 = 145.67), followed by Turkey (Q1 = 91.8). China authored 11.95 maternal depression-related publications per 1000 billion US$ GDP. The USA had the highest activity of maternal depression research per GDP in billion US$ per capita (Q2 = 60.86). When research activity was related to population size (Q3 = publications per Mio. inhabitants), Australia (Q3 = 26.44) was leading the field, followed by Norway (Q3 = 18.48). Gender analysis revealed a relatively high degree of female scientists involved in this field of research with pronounced differences between single subject areas. In summary, we here present the first picture of the global scientific development in maternal depression research over a period of more than 100 years. The research landscape is clearly dominated by North American and Western European countries, with only minor contribution of Asian or South American countries. PMID- 27678044 TI - Neuroticism and Fatigue 3 Months After Ischemic Stroke: A Cross-Sectional Study. AB - OBJECTIVE: To examine the relation between neuroticism and fatigue in Chinese patients with stroke. DESIGN: Cross-sectional study. SETTING: Acute stroke unit. PARTICIPANTS: Survivors of ischemic stroke (N=191) recruited from the acute stroke unit between May 1, 2010, and September 1, 2011. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The personality trait of neuroticism was measured with the neuroticism subscale of the Chinese version of the NEO Five Factor Inventory. The level of fatigue was measured with the Fatigue Assessment Scale. The National Institutes of Health Stroke Scale, Geriatric Depression Scale, Barthel Index, and Mini-Mental State Examination were administered to obtain demographic and clinical information. RESULTS: Fatigue severity 3 months after stroke positively correlated with Geriatric Depression Scale and NEO Five Factor Inventory neuroticism scores and negatively correlated with the Barthel Index score. CONCLUSIONS: Neuroticism, independent of depressive symptoms, is a predictor of fatigue severity 3 months after stroke. Interventions such as psychological screening programs are warranted for early detection of patients at high risk of poststroke depression. PMID- 27678045 TI - Occurrence of new psychoactive substances in wastewater of major Chinese cities. AB - New psychoactive substances have become increasingly popular across the globe in recent years, which may cause certain public health issues. In this work, sewage based epidemiology was applied to examine the use of two synthetic cathinones, mephedrone and methylenedioxypyrovalerone (MDPV), and three piperazines, benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP), and 1-(3 Chlorophenyl)piperazine (mCPP), across China. Influent wastewater samples were collected from 36 sewage treatment plants (STPs) in 18 major cities that cover all the geographic regions of the country. Effluent samples were also collected from selected STPs to determine removal rates. Mephedrone, TFMPP, and mCPP were below detection limits in all the wastewater samples collected, indicating negligible use of these substances in China. MDPV was detected in wastewater at 13 STPs. However, its loads were <1mg/1000inh/d at most of these STPs, indicating low use of this substance. BZP was detected at all the STPs examined, with loads typically falling within the range of 3-10mg/1000inh/d. No clear geographic pattern in BZP occurrence in wastewater was identified. Since BZP in wastewater may also come from its legal sources, whether widespread occurrence of BZP means widespread abuse is yet to be confirmed. Apparent removal of MDPV by wastewater treatment was low (<25%), whereas removal of BZP was nearly complete (typically>95%). PMID- 27678046 TI - An evaluation tool kit of air quality micro-sensing units. AB - Recent developments in sensory and communication technologies have made the development of portable air-quality (AQ) micro-sensing units (MSUs) feasible. These MSUs allow AQ measurements in many new applications, such as ambulatory exposure analyses and citizen science. Typically, the performance of these devices is assessed using the mean error or correlation coefficients with respect to a laboratory equipment. However, these criteria do not represent how such sensors perform outside of laboratory conditions in large-scale field applications, and do not cover all aspects of possible differences in performance between the sensor-based and standardized equipment, or changes in performance over time. This paper presents a comprehensive Sensor Evaluation Toolbox (SET) for evaluating AQ MSUs by a range of criteria, to better assess their performance in varied applications and environments. Within the SET are included four new schemes for evaluating sensors' capability to: locate pollution sources; represent the pollution level on a coarse scale; capture the high temporal variability of the observed pollutant and their reliability. Each of the evaluation criteria allows for assessing sensors' performance in a different way, together constituting a holistic evaluation of the suitability and usability of the sensors in a wide range of applications. Application of the SET on measurements acquired by 25 MSUs deployed in eight cities across Europe showed that the suggested schemes facilitates a comprehensive cross platform analysis that can be used to determine and compare the sensors' performance. The SET was implemented in R and the code is available on the first author's website. PMID- 27678047 TI - Polycyclic aromatic hydrocarbons (PAHs) in indoor dust samples from Cities of Jeddah and Kuwait: Levels, sources and non-dietary human exposure. AB - This study reports levels and profiles of polycyclic aromatic hydrocarbons (PAHs) in dust samples collected from three different microenvironments (cars, air conditioner (AC) filters and household floor dust) of Jeddah, Saudi Arabia (KSA) and Kuwait. To the best of our knowledge, this is first study reporting PAHs in indoor microenvironments of KSA, which makes these findings important. Benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), phenanthrene (Phe), and pyrene (Pyr) were found to be the major chemicals in dust samples from all selected microenvironments. SigmaPAHs occurred at median concentrations (ng/g) of 3450, 2200, and 2650 in Saudi AC filter, car and household floor dust, respectively. The median levels (ng/g) of SigmaPAHs in Kuwaiti car (950) and household floor (1675) dust samples were lower than Saudi dust. The PAHs profile in Saudi dust was dominated by high molecular weight (HMW) (4-5 ring) PAHs while in Kuwaiti dust 3 ring PAHs have marked contribution. BaP equivalent, a marker for carcinogenic PAHs, was high in Saudi household floor and AC filter dust with median levels (ng/g) of 370 and 455, respectively. Different exposure scenarios, using 5th percentile, median, mean, and 95th percentile levels, were estimated for adults and toddlers. For Saudi and Kuwaiti toddlers worst exposure scenario of SigmaPAHs was calculated at 175 and 85ng/kg body weight/day (ng/kgbw/d), respectively. For Saudi toddlers, the calculated worst exposure scenarios for carcinogenic BaP (27.7) and BbF (29.3ng/kgbw/d) was 2-4 times higher than Kuwaiti toddlers. This study is based on small number of samples which necessitate more detailed studies for better understanding of dynamics of PAHs in the indoor environments of this region. Nevertheless, our finding supports the ongoing exposure of organic pollutants to population that accumulates indoor. PMID- 27678048 TI - Using in-situ optical sensors to study dissolved organic carbon dynamics of streams and watersheds: A review. AB - It is important to understand how dissolved organic carbon (DOC) is processed and transported through stream networks because DOC is a master water quality variable in aquatic ecosystems. High-frequency sampling is necessary to capture important, rapid shifts in DOC source, concentration, and composition (i.e. quality) in streams. Until recently, this high-frequency sampling was logistically difficult or impossible. However, this type of sampling can now be conducted using in-situ optical measurements through long-term, field-deployable fluorometers and spectrophotometers. The optical data collected from these instruments can quantify both DOC concentration and composition properties (e.g., specific ultra-violet absorbance at 254nm, spectral slope ratio, and fluorescence index). Previously, the use of these sensors was limited to a small number of specialized users, mainly in Europe and North America, where they were used predominantly in marine DOC studies as well as water treatment and management infrastructure. However, recent field demonstrations across a wide range of river systems reveals a large potential for the use of these instruments in freshwater environments, heightening interest and demand across multiple environmental research and management disciplines. Hence, this review provides an up-to-date synthesis on 1) the use of spectroscopy as a diagnostic tool in stream DOC studies, 2) the instrumentation, its applications, potential limitations and future considerations, and 3) the new watershed DOC research directions made possible via these in-situ optical sensors. PMID- 27678049 TI - Management of post-operative Crohn's disease in 2017: where do we go from here? AB - INTRODUCTION: Postoperative recurrence (POR) of Crohn's disease is common after surgical resection. How to best manage POR remains uncertain. Areas covered: In this review, we will first describe the natural course and the best modalities to diagnose this surgical sequela. We will then focus on the potential risk factors for relapse and highlight the main shortcomings in the current study designs and endoscopic and clinical scoring systems, which may partly explain the unexpected outcomes of recent clinical trials. Finally, we will propose a strategy to address the management of POR. Expert commentary: Anti-tumor necrosis factor (Anti-TNF) agents are the most effective therapy to prevent POR in Crohn's disease. Patient risk stratification and active monitoring with scheduled ileocolonoscopy are cornerstones of optimal POR management. Further studies are needed to address areas of uncertainty including timing and duration of therapy and the role of therapeutic drug monitoring in this setting. PMID- 27678050 TI - Wave-induced loss of ultra-relativistic electrons in the Van Allen radiation belts. AB - The dipole configuration of the Earth's magnetic field allows for the trapping of highly energetic particles, which form the radiation belts. Although significant advances have been made in understanding the acceleration mechanisms in the radiation belts, the loss processes remain poorly understood. Unique observations on 17 January 2013 provide detailed information throughout the belts on the energy spectrum and pitch angle (angle between the velocity of a particle and the magnetic field) distribution of electrons up to ultra-relativistic energies. Here we show that although relativistic electrons are enhanced, ultra-relativistic electrons become depleted and distributions of particles show very clear telltale signatures of electromagnetic ion cyclotron wave-induced loss. Comparisons between observations and modelling of the evolution of the electron flux and pitch angle show that electromagnetic ion cyclotron waves provide the dominant loss mechanism at ultra-relativistic energies and produce a profound dropout of the ultra-relativistic radiation belt fluxes. PMID- 27678052 TI - A novel sequential electrostatic-HILIC SPE within a quantitative method for bivalirudin in human plasma by LC-SRM. AB - AIM: This work set out to realize an idea for a novel means of extracting the peptide therapeutic bivalirudin from human plasma in what would be a uniquely selective means of SPE, a mixed-mode protocol involving electrostatic interactions followed by HILIC. RESULTS: Inter and intra-assay relative error ranged from 3.52 to 8.23%, and 2.37 to 6.90%, respectively. Inter and intra-assay precision ranged from 2.64 to 7.12%, and 0.855 to 2.90%, respectively. Recoveries of 80% were attained, and there was no hint of discernible manifestation of matrix effects. CONCLUSION: The method was shown to perform excellently in the assessment tantamount to method validation. The essence of the extraction method presents a new option for highly selective extraction of peptides from biological matrices. PMID- 27678051 TI - Role of E2-RING Interactions in Governing RNF4-Mediated Substrate Ubiquitination. AB - Members of the really interesting new gene (RING) E3 ubiquitin ligase family bind to both substrate and ubiquitin-charged E2 enzyme, promoting the transfer of ubiquitin from the E2 to substrate. Either a single ubiquitin or one of the several types of polyubiquitin chains can be conjugated to substrate proteins, with different types of ubiquitin modifications signaling the distinct outcomes. E2 enzymes play a central role in governing the nature of the ubiquitin modification, although the essential features of the E2 that differentiate mono- versus polyubiquitinating E2 enzymes remain unclear. RNF4 is a compact RING E3 ligase that directs the ubiquitination of polySUMO chains in concert with several different E2 enzymes. RNF4 monoubiquitinates polySUMO substrates in concert with RAD6B and polyubiquitinates substrates together with UBCH5B, a promiscuous E2 that can function with a broad range of E3 ligases. We find that the divergent ubiquitination activities of RAD6B and UBCH5B are governed by differences at the RING-binding surface of the E2. By mutating the RAD6B RING-binding surface to resemble that of UBCH5B, RAD6B can be transformed into a highly active UBCH5B like E2 that polyubiquitinates SUMO chains in concert with RNF4. The switch in RAD6B activity correlates with increased affinity of the E2 for RNF4. These results point to an important role of the affinity between an E3 and its cognate E2 in governing the multiplicity of substrate ubiquitination. PMID- 27678054 TI - Endoplasmic reticulum stress affects the transport of phosphatidylethanolamine from mitochondria to the endoplasmic reticulum in S.cerevisiae. AB - Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are two of the most abundant phospholipids in cells. Although both lipids can be synthesized in the endoplasmic reticulum (ER), in S. cerevisiae PE can also be produced in mitochondria and endosomes; this PE can be transported back to the ER where it is converted to PC. In this study we found that dithiothreitol (DTT), which induces ER stress, decreases PE export from mitochondria to the ER. This results in decreased levels of total cellular PC and mitochondrial PC. These decreases were not caused by changes in levels of PC synthesizing or degrading enzymes. PE export from mitochondria to the ER during ER stress was further reduced in cells lacking Mdm10p, a component of an ER-mitochondrial tethering complex that may facilitated lipid exchange between these compartments. We also found that reducing mitochondrial PC levels induces mitophagy. In conclusion, we show that ER stress affected PE export from mitochondria to ER and the Mdm10p is important for this process. PMID- 27678055 TI - Persistence of fan-shaped keratocytes is a matrix-rigidity-dependent mechanism that requires alpha5beta1 integrin engagement. AB - Despite the importance of matrix rigidity on cell functions, many aspects of the mechanosensing process in highly migratory cells remain elusive. Here, we studied the migration of highly motile keratocytes on culture substrates with similar biochemical properties and rigidities spanning the range between soft tissues (~kPa) and stiff culture substrates (~GPa). We show that morphology, polarization and persistence of motile keratocytes are regulated by the matrix stiffness over seven orders of magnitude, without changing the cell spreading area. Increasing the matrix rigidity leads to more F-actin in the lamellipodia and to the formation of mature contractile actomyosin fibers that control the cell rear retraction. Keratocytes remain rounded and form nascent adhesions on compliant substrates, whereas large and uniformly distributed focal adhesions are formed on fan-shaped keratocytes migrating on rigid surfaces. By combining poly-L-lysine, fibronectin and vitronectin coatings with selective blocking of alphavbeta3 or alpha5beta1 integrins, we show that alphaVbeta3 integrins permit the spreading of keratocytes but are not sufficient for polarization and rigidity sensing that require the engagement of alpha5beta1 integrins. Our study demonstrates a matrix rigidity-dependent regulation of the directional persistence in motile keratocytes and refines the role of alphavbeta3 and alpha5beta1 integrins in the molecular clutch model. PMID- 27678053 TI - Epistasis and Pleiotropy Affect the Modularity of the Genotype-Phenotype Map of Cross-Resistance in HIV-1. AB - The genotype-phenotype (GP) map is a central concept in evolutionary biology as it describes the mapping of molecular genetic variation onto phenotypic trait variation. Our understanding of that mapping remains partial, especially when trying to link functional clustering of pleiotropic gene effects with patterns of phenotypic trait co-variation. Only on rare occasions have studies been able to fully explore that link and tend to show poor correspondence between modular structures within the GP map and among phenotypes. By dissecting the structure of the GP map of the replicative capacity of HIV-1 in 15 drug environments, we provide a detailed view of that mapping from mutational pleiotropic variation to phenotypic co-variation, including epistatic effects of a set of amino-acid substitutions in the reverse transcriptase and protease genes. We show that epistasis increases the pleiotropic degree of single mutations and provides modularity to the GP map of drug resistance in HIV-1. Moreover, modules of epistatic pleiotropic effects within the GP map match the phenotypic modules of correlated replicative capacity among drug classes. Epistasis thus increases the evolvability of cross-resistance in HIV by providing more drug- and class specific pleiotropic profiles to the main effects of the mutations. We discuss the implications for the evolution of cross-resistance in HIV. PMID- 27678056 TI - Repurposing clinically approved cephalosporins for tuberculosis therapy. AB - While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug. Synergy was observed even under intracellular growth conditions where beta-lactams typically have limited activities. Cephalosporins and rifampicin were 4- to 64-fold more active in combination than either drug alone; however, limited synergy was observed with rifapentine or rifabutin. Clavulanate was a key synergistic partner in triple combinations. Cephalosporins (and other beta-lactams) together with clavulanate rescued the activity of rifampicin against a rifampicin resistant strain. Synergy was not due exclusively to increased rifampicin accumulation within the mycobacterial cells. Cephalosporins were also synergistic with new anti-TB drugs such as bedaquiline and delamanid. Studies will be needed to validate their in vivo activities. However, the fact that cephalosporins are orally bioavailable with good safety profiles, together with their anti-mycobacterial activities reported here, suggest that they could be repurposed within new combinatorial TB therapies. PMID- 27678058 TI - Erratum to: The influence of travel time on emergency obstetric care seeking behavior in the urban poor of Bangladesh: a GIS study. PMID- 27678057 TI - Evidence for Direct Control of Virulence and Defense Gene Circuits by the Pseudomonas aeruginosa Quorum Sensing Regulator, MvfR. AB - Pseudomonas aeruginosa defies eradication by antibiotics and is responsible for acute and chronic human infections due to a wide variety of virulence factors. Currently, it is believed that MvfR (PqsR) controls the expression of many of these factors indirectly via the pqs and phnAB operons. Here we provide strong evidence that MvfR may also bind and directly regulate the expression of additional 35 loci across the P. aeruginosa genome, including major regulators and virulence factors, such as the quorum sensing (QS) regulators lasR and rhlR, and genes involved in protein secretion, translation, and response to oxidative stress. We show that these anti-oxidant systems, AhpC-F, AhpB-TrxB2 and Dps, are critical for P. aeruginosa survival to reactive oxygen species and antibiotic tolerance. Considering that MvfR regulated compounds generate reactive oxygen species, this indicates a tightly regulated QS self-defense anti-poisoning system. These findings also challenge the current hierarchical regulation model of P. aeruginosa QS systems by revealing new interconnections between them that suggest a circular model. Moreover, they uncover a novel role for MvfR in self defense that favors antibiotic tolerance and cell survival, further demonstrating MvfR as a highly desirable anti-virulence target. PMID- 27678059 TI - Effects of an 8-year childhood physical activity intervention on musculoskeletal gains and fracture risk. AB - BACKGROUND: Physical activity (PA) in childhood is associated with musculoskeletal benefits while the effect on fracture risk is yet to be determined. The aim of this study was to evaluate whether extension of a PA intervention leads to improvement in musculoskeletal traits with an accompanied reduced fracture risk. We hypothesized that the PA program would have beneficial effects in both sexes, but more so in girls since they tend to be less physically active than boys during this time frame. METHODS: In one elementary school we increased physical education (PE) from 60 to 200min per school week and followed 65 girls and 93 boys from a mean age of 7years until a mean age of 15years. Thirty-nine girls and 37 boys in three other schools continued with 60min of PE per week during the same years and served as controls. We measured bone mineral content (BMC), areal bone mineral density (aBMD), and bone area annually with dual energy X-ray absorptiometry, and leg muscle strength with a computerized dynamometer. In 3534 children within the same PE program (1339 in the intervention and 2195 in the control group) we registered incident fractures during the 8-year study period and estimated annual sex-specific fracture incidence rate ratios (IRRs). RESULTS: Girls in the intervention group annually gained more total body less head aBMD, spine aBMD (p<0.01), femoral neck BMC (p<0.05), lumbar vertebrae size (p<0.05), and knee flexion strength (p<0.05) than girls in the control cohort. In boys we found no group differences. There was an inverse correlation between number of years with extra PE and the annual IRR of sustaining fractures in both girls (r=-0.90 (95% CI -0.98 to -0.51); p<0.001) and boys (r=-0.74 (95% CI -0.94 to -0.02); p<0.05). CONCLUSION: In this 8-year pediatric school-based moderate exercise intervention program there is an inverse correlation in both sexes between annual IRR and each additional year of extra PA. A sub-cohort of girls in the intervention group had greater gains in bone mass, bone size, and muscle strength, which could possibly explain the inverse correlation between years within the PA program and fracture risk, while in boys the reason for the inverse correlation remains unknown. It should be noted that differences in unreported factors such as skeletal maturity status, diet, and spare time PA could confound our inferences. That is, true causality cannot be stated. PMID- 27678060 TI - Characterization of aspartyl aminopeptidase from Toxoplasma gondii. AB - Aminopeptidases have emerged as new promising drug targets for the development of novel anti-parasitic drugs. An aspartyl aminopeptidase-like gene has been identified in the Toxoplasma gondii genome (TgAAP), although its function remains unknown. In this study, we characterized TgAAP and performed functional analysis of the gene product. Firstly, we expressed a functional recombinant TgAAP (rTgAAP) protein in Escherichia coli, and found that it required metal ions for activity and showed a substrate preference for N-terminal acidic amino acids Glu and Asp. Then, we evaluated the function and drug target potential of TgAAP using the CRISPR/Cas9 knockout system. Western blotting demonstrated the deletion of TgAAP in the knockout strain. Indirect immunofluorescence analysis showed that TgAAP was localized in the cytoplasm of the wild-type parasite, but was not expressed in the knockout strain. Phenotype analysis revealed that TgAAP knockout inhibited the attachment/invasion, replication, and substrate-specific activity in T. gondii. Finally, the activity of drug CID 23724194, previously described as targeting Plasmodium and malarial parasite AAP, was tested against rTgAAP and the parasite. Overall, TgAAP knockout affected the growth of T. gondii but did not completely abolish parasite replication and growth. Therefore, TgAAP may comprise a useful adjunct drug target of T. gondii. PMID- 27678061 TI - Comparing 3-month recall to daily reporting of sexual behaviours. AB - OBJECTIVES: This study aimed to examine discrepancies between self-report methods and methodological issues related to sexual risk taking. We examined sexual behaviour assessed via 3-month electronic recall and by daily electronic reporting among a large cohort of patients attending STI clinics. METHODS: STI clinic attenders (N= 628) aged 15 to 60 years reported on demographic information (at baseline), penile-vaginal sex acts, condom-unprotected penile-vaginal sex and STI history using 3-month recall and daily reports. Additionally, interviewer participant match related to race and gender, as well as study site were considered as covariates. RESULTS: Concordance between recall and daily reports on penile-vaginal sex was moderately strong (Spearman's r (rs)=0.62; p<0.001). Comparison for reports for condom-unprotected penile-vaginal sex resulted in a correlation coefficient of 0.61 (p<0.001), also indicating moderately strong agreement between the two methods. Two generalised logit models were conducted to explain lack of strong concordance in penile-vaginal sex acts and condom unprotected penile-vaginal sex. The odds of a female reporting higher frequency of sex in daily reports compared with recall were more than two times that of a male. Every five person increase in the number of lifetime sexual partners was associated with five times the odds of a discrepancy in reporting methods. Age was also significantly associated with unequal daily versus recall sex frequency reporting. CONCLUSIONS: Shifting focus to methodological considerations of technological reports can help ensure better investment of resources into sexual health research due to greater understanding of the methodological properties of data collection methods. PMID- 27678062 TI - Aguamiel concentrate from Agave salmiana and its extracted saponins attenuated obesity and hepatic steatosis and increased Akkermansia muciniphila in C57BL6 mice. AB - Obesity and its comorbidities are a severe public health problem worldwide. The use of bioactive compounds found in some foods has been demonstrated to ameliorate the metabolic abnormalities associated with obesity. The purpose of this study was to assess whether the bioactive compounds present in aguamiel concentrate (AC) from Agave salmiana could attenuate glucose intolerance and hepatic steatosis in mice fed a high fat (HF) diet. HPLC-ELSD analysis showed that AC contained several saponins. The consumption of an AC extract rich in saponins reduced weight gain and fat mass and lowered serum glucose, insulin and LDL-cholesterol levels in mice fed a HF diet. Additionally, mice fed the saponin extract exhibited a reduced HOMA index and hepatic lipid levels and increased expression of genes involved in fatty acid oxidation. Saponins increased white adipose tissue browning, AMPK phosphorylation, fatty acid oxidation, and mitochondrial activity in skeletal muscle and energy expenditure in mice fed the HF diet. These metabolic changes were accompanied by an increase in the abundance of Akkermansia muciniphila in the gut microbiota. Therefore, Agave salmiana saponins can be an alternative to attenuate the metabolic changes that accompany obesity. PMID- 27678064 TI - Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin. AB - Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702. Gene expression profiling identified the apoptotic pathway as the major cause of hepatotoxicity induced by TBT. Flow cytometry assays confirmed that medium- and high-dose TBT treatments significantly increased the number of apoptotic cells, and more cells underwent late apoptosis in the high-dose TBT group. The genes encoding heat shock proteins (HSPs), kinases and tumor necrosis factor receptors mediated TBT-induced apoptosis. These findings revealed novel molecular mechanisms of TBT-induced hepatotoxicity, and the current microarray data may also provide clues for future studies. PMID- 27678063 TI - Cardiovascular Disease Chemogenomics Knowledgebase-guided Target Identification and Drug Synergy Mechanism Study of an Herbal Formula. AB - Combination therapy is a popular treatment for various diseases in the clinic. Among the successful cases, Traditional Chinese Medicinal (TCM) formulae can achieve synergistic effects in therapeutics and antagonistic effects in toxicity. However, characterizing the underlying molecular synergisms for the combination of drugs remains a challenging task due to high experimental expenses and complication of multicomponent herbal medicines. To understand the rationale of combination therapy, we investigated Sini Decoction, a well-known TCM consisting of three herbs, as a model. We applied our established diseases-specific chemogenomics databases and our systems pharmacology approach TargetHunter to explore synergistic mechanisms of Sini Decoction in the treatment of cardiovascular diseases. (1) We constructed a cardiovascular diseases-specific chemogenomics database, including drugs, target proteins, chemicals, and associated pathways. (2) Using our implemented chemoinformatics tools, we mapped out the interaction networks between active ingredients of Sini Decoction and their targets. (3) We also in silico predicted and experimentally confirmed that the side effects can be alleviated by the combination of the components. Overall, our results demonstrated that our cardiovascular disease-specific database was successfully applied for systems pharmacology analysis of a complicated herbal formula in predicting molecular synergetic mechanisms, and led to better understanding of a combinational therapy. PMID- 27678066 TI - Diabetes in Racial and Ethnic Minorities in the United States: Individualizing Approaches to Diagnosis and Management. AB - Diabetes is a growing health epidemic in the United States. Racial and ethnic minorities are disproportionately affected by diabetes and associated comorbidities and complications. The present review article aims to characterize the various ways in which minority populations are affected by diabetes. We address differences in prevalence of diabetes and associated conditions that include cardiovascular disease, hypertension, microvascular complications, and mortality. Additionally, we discuss factors that contribute to disparate diabetes related outcomes, including physiology, culture and healthsystems. Finally, we look at outcomes of various interventions taken to address health disparities in diabetes care, specifically in racial and ethnic minority populations. PMID- 27678065 TI - The Epidemiology of Cardiovascular Disease in Adults with Type 1 Diabetes. AB - BACKGROUND: In the era following the publication of results from the Diabetes Control and Complications Trial / Epidemiology of Diabetes Complications (DCCT/EDIC) study, care for patients with type 1 diabetes has dramatically improved. OBJECTIVE/METHODS: The present review specifically focused on the epidemiology of cardiovascular complications among adults with type 1 diabetes, summarizing evidence on the prevalence, incidence, mortality, as well as on predictors of cardiovascular disease in this population. The review covered papers published until December 2015. CONCLUSION: Despite these significant advancements in knowledge regarding the management of this chronic disease, however, individuals with type 1 diabetes continue to experience increased morbidity and mortality compared to the general population. PMID- 27678069 TI - Gender Differences in Perceptions of Resources and Turnover Intentions of Work Linked Couples in Masculine Occupations. AB - Employees in work-linked marriages have spouses that share the same family and the same workplace and/or occupation. Whereas, in recent years, there has been increasingly more research on dual-career marriages (i.e. both spouses work, but not necessarily at the same workplace and/or occupation), there has been very little research on work-linked marriages. The current study focuses on work resources (i.e. family supportive supervisor behaviour and job control) as key mediating processes that explain the effect of gender on turnover intentions among work-linked employees in masculine occupations (i.e. military). Investigating gender differences is important because, compared with men, women are more likely to be in work-linked marriages and to leave their jobs. Based on role theory and conservation of resource theory, we predicted that gender was related to turnover intentions, and this relationship would be mediated by key explanatory variables (i.e. family supportive supervisor behaviours, job control and psychological distress). Mediation analyses, conducted on a sample of men and women in work-linked marriages (n = 309), provide support for the hypothesized model. These findings offer guidance for understanding gender differences among work-linked employees in masculine occupations, and how these differences can affect important outcomes such as turnover intentions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27678068 TI - In vivo formation of natural HgSe nanoparticles in the liver and brain of pilot whales. AB - To understand the biochemistry of methylmercury (MeHg) that leads to the formation of mercury-selenium (Hg-Se) clusters is a long outstanding challenge that promises to deepen our knowledge of MeHg detoxification and the role Se plays in this process. Here, we show that mercury selenide (HgSe) nanoparticles in the liver and brain of long-finned pilot whales are attached to Se-rich structures and possibly act as a nucleation point for the formation of large Se Hg clusters, which can grow with age to over 5 MUm in size. The detoxification mechanism is fully developed from the early age of the animals, with particulate Hg found already in juvenile tissues. As a consequence of MeHg detoxification, Se methionine, the selenium pool in the system is depleted in the efforts to maintain essential levels of Se-cysteine. This study provides evidence of so far unreported depletion of the bioavailable Se pool, a plausible driving mechanism of demonstrated neurotoxic effects of MeHg in the organism affected by its high dietary intake. PMID- 27678067 TI - Characterization and expression profiling of ATP-binding cassette transporter genes in the diamondback moth, Plutella xylostella (L.). AB - BACKGROUND: ATP-binding cassette (ABC) transporters are one of the major transmembrane protein families found in all organisms and play important roles in transporting a variety of compounds across intra and extra cellular membranes. In some species, ABC transporters may be involved in the detoxification of substances such as insecticides. The diamondback moth, Plutella xylostella (L.), a destructive pest of cruciferous crops worldwide, is an important species to study as it is resistant to many types of insecticides as well as biological control Bacillus thuringiensis toxins. RESULTS: A total of 82 ABC genes were identified from our published P. xylostella genome, and grouped into eight subfamilies (ABCA-H) based on phylogenetic analysis. Genes of subfamilies ABCA, ABCC and ABCH were found to be expanded in P. xylostella compared with those in Bombyx mori, Manduca sexta, Heliconius melpomene, Danaus plexippus, Drosophila melanogaster, Tetranychus urticae and Homo sapiens. Phylogenetic analysis indicated that many of the ABC transporters in P. xylostella are orthologous to the well-studied ABC transporter genes in the seven other species. Transcriptome- and qRT-PCR-based analysis elucidated physiological effects of ABC gene expressions of P. xylostella which were developmental stage- and tissue-specific as well as being affected by whether or not the insects were from an insecticide resistant strain. Two ABCC and one ABCA genes were preferentially expressed in midgut of the 4th-instar larvae of a susceptible strain (Fuzhou-S) suggesting their potential roles in metabolizing plant defensive chemicals. Most of the highly expressed genes in insecticide-resistant strains were also predominantly expressed in the tissues of Malpighian tubules and midgut. CONCLUSIONS: This is the most comprehensive study on identification, characterization and expression profiling of ABC transporter genes in P. xylostella to date. The diversified features and expression patterns of this gene family may be associated with the evolutionary capacity of this species to develop resistance to a wide range of insecticides and biological toxins. Our findings provide a solid foundation for future functional studies on specific ABC transporter genes in P. xylostella, and for further understanding of their physiological roles and regulatory pathways in insecticide resistance. PMID- 27678070 TI - Geographic dimensions of a health network dedicated to occupational and work related diseases. AB - BACKGROUND: Although introduced nearly 40 years ago, Geographic Information Systems (GISs) have never been used to study Occupational Health information regarding the different types, scale or sources of data. The geographic distribution of occupational diseases and underlying work activities were always analyzed independently. Our aim was to consider the French Network of Occupational Disease (OD) clinics, namely the "French National OD Surveillance and Prevention Network" (rnv3p) as a spatial object in order to describe its catchment. METHODS: We mapped rnv3p observations at the workplace level. We initially analyzed rnv3p capture with reference to its own data, then to the underlying workforce (INSEE "Employment Areas"), and finally compared its capture of one emblematic occupational disease (mesothelioma) to an external dataset provided by a surveillance system thought to be exhaustive (PNSM). RESULTS: While the whole country is covered by the network, the density of observations decreases with increase in the distance from the 31 OD clinics (located within the main French cities). Taking into account the underlying workforce, we show that the probability to capture and investigation of OD (assessed by rates of OD per 10,000 workers) also presents large discrepancies between OD clinics. This capture rate might also show differences according to the disease, as exemplified by mesothelioma. CONCLUSION: The geographic approach to this network, enhanced by the possibilities provided by the GIS tool, allow a better understanding of the coverage of this network at a national level, as well as the visualization of capture rates for all OD clinics. Highlighting geographic and thematic shading zones bring new perspectives to the analysis of occupational health data, and should improve occupational health vigilance and surveillance. PMID- 27678073 TI - Inadequate reporting of statistical results. PMID- 27678071 TI - Prediction of new drug indications based on clinical data and network modularity. AB - Drug repositioning is commonly done within the drug discovery process in order to adjust or expand the application line of an active molecule. Previous computational methods in this domain mainly focused on shared genes or correlations between genes to construct new drug-disease associations. We propose a method that can not only handle drugs or diseases with or without related genes but consider the network modularity. Our method firstly constructs a drug network and a disease network based on side effects and symptoms respectively. Because similar drugs imply similar diseases, we then cluster the two networks to identify drug and disease modules, and connect all possible drug-disease module pairs. Further, based on known drug-disease associations in CTD and using local connectivity of modules, we predict potential drug-disease associations. Our predictions are validated by testing their overlaps with drug indications reported in published literatures and CTD, and KEGG enrichment analysis are also made on their related genes. The experimental results demonstrate that our approach can complement the current computational approaches and its predictions can provide new clues for the candidate discovery of drug repositioning. PMID- 27678072 TI - Does Increased Medication Use among Seniors Increase Risk of Hospitalization and Emergency Department Visits? AB - OBJECTIVE: To examine the extent of the health risks of consuming multiple medications among the older population. DATA SOURCES/STUDY SETTING: Secondary data from the period 2004-2006. The study setting was the province of Ontario, Canada, and the sample consisted of individuals aged 65 years or older who responded to a national health survey. STUDY DESIGN: We estimated a system of equations for inpatient and emergency department (ED) services to test the marginal effect of medication use on hospital services. We controlled for endogeneity in medication use with a two-stage residual inclusion approach appropriate for nonlinear models. PRINCIPAL FINDINGS: Increased prescription drug use has the effect of increasing the likelihood of both being admitted into hospital and visiting a hospital ED. Each additional medication is associated with a 2-3 percent increase in the likelihood of hospitalization and a 3-4 percent increase in the likelihood of an ED visit, after controlling for past utilization, health status, the endogeneity of medication use, and the unobserved factors that may affect the use of both services. CONCLUSIONS: Multiple medications appear to increase the risk of hospitalization among seniors covered by a universal prescription drug plan. These results raise questions about the appropriateness of medication use and the need for increased oversight of current prescribing practices. PMID- 27678074 TI - Strategies to Increase Rigor and Reproducibility of Data in Manuscripts: Reply to Heroux. PMID- 27678075 TI - Nanowire formation is preceded by nanotube growth in templated electrodeposition of cobalt hybrid nanostructures. AB - Cobalt fluted nanowires, novel nanostructures with a diameter of 200 nm consisting of a solid nanowire base and a thin, nanotubular flute shape, were grown in track-etched polycarbonate membranes via templated electrodeposition. The structures were characterized electrochemically via cyclic voltammetry, chronoamperometry, and charge stripping, and structurally via scanning electron microscopy, transmission electron microscopy, and focused ion beam cross sectioning. Electrochemical and structural analysis reveals details of their deposition kinetics, structure, and morphology, and indicate possible mechanisms for their formation and control. These unique structures provide inspiration for an array of possible applications in electronics, photonics, and other fields. PMID- 27678076 TI - A drug target slim: using gene ontology and gene ontology annotations to navigate protein-ligand target space in ChEMBL. AB - BACKGROUND: The process of discovering new drugs is a lengthy, time-consuming and expensive process. Modern day drug discovery relies heavily on the rapid identification of novel 'targets', usually proteins that can be modulated by small molecule drugs to cure or minimise the effects of a disease. Of the 20,000 proteins currently reported as comprising the human proteome, just under a quarter of these can potentially be modulated by known small molecules Storing information in curated, actively maintained drug discovery databases can help researchers access current drug discovery information quickly. However with the increase in the amount of data generated from both experimental and in silico efforts, databases can become very large very quickly and information retrieval from them can become a challenge. The development of database tools that facilitate rapid information retrieval is important to keep up with the growth of databases. DESCRIPTION: We have developed a Gene Ontology-based navigation tool (Gene Ontology Tree) to help users retrieve biological information to single protein targets in the ChEMBL drug discovery database. 99 % of single protein targets in ChEMBL have at least one GO annotation associated with them. There are 12,500 GO terms associated to 6200 protein targets in the ChEMBL database resulting in a total of 140,000 annotations. The slim we have created, the 'ChEMBL protein target slim' allows broad categorisation of the biology of 90 % of the protein targets using just 300 high level, informative GO terms. We used the GO slim method of assigning fewer higher level GO groupings to numerous very specific lower level terms derived from the GOA to describe a set of GO terms relevant to proteins in ChEMBL. We then used the slim created to provide a web based tool that allows a quick and easy navigation of protein target space. Terms from the GO are used to capture information on protein molecular function, biological process and subcellular localisations. The ChEMBL database also provides compound information for small molecules that have been tested for their effects on these protein targets. The 'ChEMBL protein target slim' provides a means of firstly describing the biology of protein drug targets and secondly allows users to easily establish a connection between biological and chemical information regarding drugs and drug targets in ChEMBL. The 'ChEMBL protein target slim' is available as a browsable 'Gene Ontology Tree' on the ChEMBL site under the browse targets tab ( https://www.ebi.ac.uk/chembl/target/browser ). A ChEMBL protein target slim OBO file containing the GO slim terms pertinent to ChEMBL is available from the GOC website ( http://geneontology.org/page/go-slim and-subset-guide ). CONCLUSIONS: We have created a protein target navigation tool based on the 'ChEMBL protein target slim'. The 'ChEMBL protein target slim' provides a way of browsing protein targets in ChEMBL using high level GO terms that describe the molecular functions, processes and subcellular localisations of protein drug targets in drug discovery. The tool also allows user to establish a link between ontological groupings representing protein target biology to relevant compound information in ChEMBL. We have demonstrated by the use of a simple example how the 'ChEMBL protein target slim' can be used to link biological processes with drug information based on the information in the ChEMBL database. The tool has potential to aid in areas of drug discovery such as drug repurposing studies or drug-disease-protein pathways. PMID- 27678078 TI - Cross-linking in children with keratoconus: a systematic review and meta analysis. AB - Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE(r) and Cochrane databases were searched for all studies examining the effects of standard, trans epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (+/-1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness. PMID- 27678077 TI - Structural and functional characterization of a calcium-activated cation channel from Tsukamurella paurometabola. AB - The selectivity filter is an essential functional element of K+ channels that is highly conserved both in terms of its primary sequence and its three-dimensional structure. Here, we investigate the properties of an ion channel from the Gram positive bacterium Tsukamurella paurometabola with a selectivity filter formed by an uncommon proline-rich sequence. Electrophysiological recordings show that it is a non-selective cation channel and that its activity depends on Ca2+ concentration. In the crystal structure, the selectivity filter adopts a novel conformation with Ca2+ ions bound within the filter near the pore helix where they are coordinated by backbone oxygen atoms, a recurrent motif found in multiple proteins. The binding of Ca2+ ion in the selectivity filter controls the widening of the pore as shown in crystal structures and in molecular dynamics simulations. The structural, functional and computational data provide a characterization of this calcium-gated cationic channel. PMID- 27678082 TI - Editorial. PMID- 27678079 TI - The cost-effectiveness of hospital-based telephone coaching for people with type 2 diabetes: a 10 year modelling analysis. AB - BACKGROUND: Type 2 diabetes (T2DM) is a burdensome condition for individuals to live with and an increasingly costly condition for health services to treat. Cost effective treatment strategies are required to delay the onset and slow the progression of diabetes related complications. The Diabetes Telephone Coaching Study (DTCS) demonstrated that telephone coaching is an intervention that may improve the risk factor status and diabetes management practices of people with T2DM. Measuring the cost effectiveness of this intervention is important to inform funding decisions that may facilitate the translation of this research into clinical practice. The purpose of this study is to assess the cost effectiveness of telephone coaching, compared to usual diabetes care, in participants with poorly controlled T2DM. METHODS: A cost utility analysis was undertaken using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model to extrapolate outcomes collected at 6 months in the DTCS over a 10 year time horizon. The intervention's impact on life expectancy, quality-adjusted life expectancy (QALE) and costs was estimated. Costs were reported from a health system perspective. A 5 % discount rate was applied to all future costs and effects. One-way sensitivity analyses were conducted to reflect uncertainty surrounding key input parameters. RESULTS: The intervention dominated the control condition in the base-case analysis, contributing to cost savings of $3327 per participant, along with non-significant improvements in QALE (0.2 QALE) and life expectancy (0.3 years). CONCLUSIONS: The cost of delivering the telephone coaching intervention continuously, for 10 years, was fully recovered through cost savings and a trend towards net health benefits. Findings of cost savings and net health benefits are rare and should prove attractive to decision makers who will determine whether this intervention is implemented into clinical practice. TRIAL REGISTRATION: ACTRN12609000075280. PMID- 27678081 TI - The role of hypoxia-inducible factor-1alpha in zinc oxide nanoparticle-induced nephrotoxicity in vitro and in vivo. AB - BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. RESULTS: We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of apoptosis and autophagy. Interestingly, the ROS-induced hypoxia-inducible factor 1alpha (HIF-1alpha) signaling pathway was significantly increased following ZnO NPs exposure. Additionally, connective tissue growth factor (CTGF) and plasminogen activator inhibitor-1 (PAI-1), which are directly regulated by HIF-1 and are involved in the pathogenesis of kidney diseases, displayed significantly increased levels following ZnO NPs exposure in HEK-293 cells. HIF-1alpha knockdown resulted in significantly decreased levels of autophagy and increased cytotoxicity. Therefore, our results suggest that HIF-1alpha may have a protective role in adaptation to the toxicity of ZnO NPs in kidney cells. In an animal study, fluorescent ZnO NPs were clearly observed in the liver, lungs, kidneys, spleen and heart. ZnO NPs caused histopathological lesions in the kidney and increase in serum creatinine and blood urea nitrogen (BUN) which indicate possible renal possible damage. Moreover, ZnO NPs enhanced the HIF-1alpha signaling pathway, apoptosis and autophagy in mouse kidney tissues. CONCLUSIONS: ZnO NPs may cause nephrotoxicity, and the results demonstrate the importance of considering the toxicological hazards of ZnO NP production and application, especially for medicinal use. PMID- 27678083 TI - Nickel Bis(diselenolene) as a Catalyst for Olefin Purification. AB - Nickel bis(dithiolene) reversibly binds olefins via a known interligand binding mechanism, but the complex has limited practical use, due to a competitive intraligand addition which results in decomposition. The present work examines an alternative nickel-based complex that eliminates the decomposition route. Specifically, we have examined the olefin binding processes of nickel bis(diselenolene) complexes using modern density functional theory. Both the inter- and intraligand adducts of the nickel bis(diselenolenes) are thermodynamically more stable than their dithiolene analogues. We have predicted that nickel bis(diselenolene) complexes do not decompose after the intraligand addition, and that the overall activation energies for the kinetically accessible products are quite small. In short, our computational work predicts that nickel bis(diselenolene) complexes are better electrocatalysts for olefin purification than the previous candidates, superior to the previously studied nickel bis(dithiolene) complexes. PMID- 27678080 TI - Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. AB - BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >=1.6, normalized left ventricular internal diameter in diastole >=1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit. PMID- 27678084 TI - Evaluating Google Flu Trends in Latin America: Important Lessons for the Next Phase of Digital Disease Detection. AB - BACKGROUND: Latin America has a substantial burden of influenza and rising Internet access and could benefit from real-time influenza epidemic prediction web tools such as Google Flu Trends (GFT) to assist in risk communication and resource allocation during epidemics. However, there has never been a published assessment of GFT's accuracy in most Latin American countries or in any low- to middle-income country. Our aim was to evaluate GFT in Argentina, Bolivia, Brazil, Chile, Mexico, Paraguay, Peru, and Uruguay. METHODS: Weekly influenza-test positive proportions for the eight countries were obtained from FluNet for the period January 2011-December 2014. Concurrent weekly Google-predicted influenza activity in the same countries was abstracted from GFT. Pearson correlation coefficients between observed and Google-predicted influenza activity trends were determined for each country. Permutation tests were used to examine background seasonal correlation between FluNet and GFT by country. RESULTS: There were frequent GFT prediction errors, with correlation ranging from r = -0.53 to 0.91. GFT-predicted influenza activity best correlated with FluNet data in Mexico follow by Uruguay, Argentina, Chile, Brazil, Peru, Bolivia and Paraguay. Correlation was generally highest in the more temperate countries with more regular influenza seasonality and lowest in tropical regions. A substantial amount of autocorrelation was noted, suggestive that GFT is not fully specific for influenza virus activity. CONCLUSIONS: We note substantial inaccuracies with GFT-predicted influenza activity compared with FluNet throughout Latin America, particularly among tropical countries with irregular influenza seasonality. Our findings offer valuable lessons for future Internet-based biosurveillance tools. PMID- 27678086 TI - Editorial Commentary: Perspectives on the Future of Internet Search Engines and Biosurveillance Systems. PMID- 27678085 TI - The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review and Meta-analysis. AB - BACKGROUND: Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs. METHODS: We searched PubMed, CINAHL, Web of Science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes between mRDT and conventional microbiology methods. RESULTS: Thirty-one studies were included with 5920 patients. The mortality risk was significantly lower with mRDT than with conventional microbiology methods (odds ratio [OR], 0.66; 95% confidence interval [CI], .54-.80), yielding a number needed to treat of 20. The mortality risk was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR, 0.64; 95% CI, .51-.79), and non-ASP studies failed to demonstrate a significant decrease in mortality risk (0.72; .46-1.12). Significant decreases in mortality risk were observed with both gram-positive (OR, 0.73; 95% CI, .55-.97) and gram-negative organisms (0.51; .33-.78) but not yeast (0.90; .49-1.67). Time to effective therapy decreased by a weighted mean difference of -5.03 hours (95% CI, -8.60 to -1.45 hours), and length of stay decreased by -2.48 days (-3.90 to -1.06 days). CONCLUSIONS: For BSIs, mRDT was associated with significant decreases in mortality risk in the presence of a ASP, but not in its absence. mRDT also decreased the time to effective therapy and the length of stay. mRDT should be considered as part of the standard of care in patients with BSIs. PMID- 27678087 TI - In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. AB - Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. Neuroplasticity can be affected by neuroactive medications and by aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on cognitive functions in both pre clinical and clinical studies. In rodent studies, vortioxetine increases glutamate neurotransmission, promotes dendritic branching and spine maturation, and elevates hippocampal expression of the activity-regulated cytoskeleton associated protein (Arc/Arg3.1) at the transcript level. The present study aims to assess the effects of vortioxetine on several neuroplasticity-related molecules in different experimental systems. Chronic (1 month) vortioxetine increased Arc/Arg3.1 protein levels in the cortical synaptosomes of young and middle-aged mice. In young mice, this was accompanied by an increase in actin depolymerizing factor (ADF)/cofilin serine 3 phosphorylation without altering the total ADF/cofilin protein level, and an increase in the GluA1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor phosphorylation at serine 845 (S845) without altering serine 831 (S831) GluA1 phosphorylation nor the total GluA1 protein level. Similar effects were detected in cultured rat hippocampal neurons: Acute vortioxetine increased S845 GluA1 phosphorylation without changing S831 GluA1 phosphorylation or the total GluA1 protein level. These changes were accompanied by an increase in alpha subunit of Ca2+/calmodulin-dependent kinase (CaMKIIalpha) phosphorylation (at threonine 286) without changing the total CaMKIIalpha protein level in cultured neurons. In addition, chronic (1 month) vortioxetine, but not fluoxetine, restored the age associated reduction in Arc/Arg3.1 and c-Fos transcripts in the frontal cortex of middle-aged mice. Taken together, these results demonstrated that vortioxetine modulates molecular targets that are related to neuroplasticity. PMID- 27678088 TI - Neurobehavioural sequelae of social deprivation in rodents revisited: Modelling social adversity for developmental neuropsychiatric disorders. AB - The significance of investigating effects of deprivation of social experience in rodents is reviewed in the context of the review by Robbins et al. (1996) in the Journal of Psychopharmacology (10: 39-47). The early development of the paradigm by which rats were reared post-weaning in social isolation is described and compared with other early experience manipulations. The specification of the neural and behavioural phenotype of the isolate is brought up-to-date, focusing on changes in motivation and cognitive function, as well as on contrasting changes in the dopamine and serotonin systems, and in cortical (including hippocampal) structure and function. The relevance of the isolate for animal models of psychiatric disorders such as attention deficit hyperactivity disorder and schizophrenia is reviewed, and it is considered that the paradigm best exemplifies a manipulation that can be applied to test effects of certain forms of social adversity during adolescence on brain development and behaviour. PMID- 27678089 TI - The effects of medication and current mood upon facial emotion recognition: findings from a large bipolar disorder cohort study. AB - OBJECTIVES: Emotional processing abnormalities have been implicated in bipolar disorder (BD) but studies are typically small and uncontrolled. Here, facial expression recognition was explored in a large and naturalistically recruited cohort of BD patients. METHODS: 271 patients with BD completed the facial expression recognition task. The effects of current medication together with the influence of current mood state and diagnostic subtype were assessed whilst controlling for the effects of demographic variables. RESULTS: Patients who were currently receiving treatment with lithium demonstrated significantly poorer accuracy in recognising angry faces, an effect that held in a monotherapy sub analysis comparing those participants on lithium only and those who were medication-free. Accuracy in recognising angry faces was also lower amongst participants currently taking dopamine antagonists (antipsychotics). Higher levels of current depressive symptoms were linked to poorer accuracy at identifying happy faces. CONCLUSION: Use of lithium and possibly dopamine antagonists may be associated with reduced processing of anger cues in BD. Findings support the existence of mood-congruent negative biases associated with depressive symptoms in BD. Observational cohort studies provide opportunities to explore the substantial effects of demographic, psychometric and clinical variables on cognitive performance and emotional processing. PMID- 27678091 TI - When can the cause of a population decline be determined? AB - Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time. PMID- 27678090 TI - Static and dynamic functional connectivity in patients with chronic fatigue syndrome: use of arterial spin labelling fMRI. AB - Studies using arterial spin labelling (ASL) have shown that individuals with chronic fatigue syndrome (CFS) have decreased regional cerebral blood flow, which may be associated with changes in functional neural networks. Indeed, recent studies indicate disruptions in functional connectivity (FC) at rest in chronically fatigued patients including perturbations in static FC (sFC), that is average FC at rest between several brain regions subserving neurocognitive, motor and affect-related networks. Whereas sFC often provides information of functional network reorganization in chronic illnesses, investigations of temporal changes in functional connectivity between multiple brain areas may shed light on the dynamic characteristics of brain network activation associated with such maladies. We used ASL fMRI in 19 patients with CFS and 15 healthy controls (HC) to examine both static and dynamic changes in FC among several a priori selected brain regions during a fatiguing cognitive task. HC showed greater increases than CFS in static FC (sFC) between insula and temporo-occipital structures and between precuneus and thalamus/striatum. Furthermore, inferior frontal gyrus connectivity to cerebellum, occipital and temporal structures declined in HC but increased in CFS. Patients also showed lower dynamic FC (dFC) between hippocampus and right superior parietal lobule. Both sFC and dFC correlated with task-related fatigue increases. These data provide the first evidence that perturbations in static and dynamic FC may underlie chronically fatigued patients' report of task induced fatigue. Further research will determine whether such changes in sFC and dFC are also characteristic for other fatigued individuals, including patients with chronic pain, cancer and multiple sclerosis. PMID- 27678092 TI - Abstracts from the 14th International Symposium on NeuroVirology October 25-28, 2016, Toronto, Ontario, Canada. PMID- 27678093 TI - Long-term follow-up of HTLV-1 proviral load in asymptomatic carriers and in incident cases of HAM/TSP: what is its relevance as a prognostic marker for neurologic disease? AB - HTLV-1 proviral load (pvl) is an important risk marker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its value as prognostic marker is not well defined. Long-term prospective cohort studies are necessary to clarify this question. Here, we analyzed HTLV-1 pvl in the peripheral blood of 82 asymptomatic carriers (AC; 351 samples), 12 HAM/TSP patients (HAM; 46 samples), and six incident cases of HAM/TSP (iHAM), with serial samples collected before (n = 10) and after (n = 20) the disease onset. The mean interval of follow-up was 10 years in the AC group and 8 years in HAM and iHAM groups. pvl was not significantly different between the first and last measurements in the three groups, but there was a trend to decrease over time. Coefficient of variation of pvl was significantly lower in the AC group than in HAM (p = 0.015) and iHAM (p = 0.022) patients. AC and HAM individuals showed a significant and strong positive correlation between the first and last measurements of pvl, but not iHAM subjects. All individuals who developed HAM/TSP during the follow-up had high pvl level (>1 %) before the onset of disease, but a typical increase in pvl was not observed in that period. The data suggest that there is a trend to reach an equilibrium plateau of pvl over time, characteristic of each individual. A significant rate of AC keeps high pvl levels for a long time without developing clinical symptoms associated to HTLV-1 infection. Thus, serial quantification of pvl in the peripheral blood does not seem to be a good prognostic marker for HAM/TSP. PMID- 27678094 TI - Genomic and Nongenomic Effects of Mifepristone at the Cardiovascular Level: A Review. AB - Mifepristone (RU 486) is a compound that is structurally related to steroid hormones, which is derived from the estrane progestins. This compound strongly binds the progesterone and glucocorticoid receptor and, to a lesser extent, the androgen receptor. This compound has its effects through different signaling pathways, related to genomic and nongenomic effects. The genomic effect involves the activation or blockage of nuclear or intracellular receptor, that in this case the progesterone, glucocorticoid, and androgen receptors. On the contrary, the nongenomic effect of mifepristone is independent of the activation of these receptors. Regarding the nongenomic, several authors observed that mifepristone induces higher uterine artery blood flow probably due to the decrease in serum nitric oxide level. Moreover, recently it has been demonstrated that mifepristone induces relaxation, and this effect is independent of the endothelium and due to the activation of the calcium channels. The main side effects associated with this pathway are hemorrhage and inhibition of platelet aggregation that can lead to hypovolemia or to hypotension. Concerning the genomic effect, this drug blocks progesterone, androgens, and glucocorticoids receptors and also activates the progesterone receptor and their respective effects. The most frequently reported adverse effects of mifepristone are nausea, vomiting, hypovolemia, hypotension, amenorrhea, and infertility. The main purpose of this review is to describe the genomic and nongenomic effects of mifepristone at vascular level and describe some pathologies in which mifepristone is used as a treatment. PMID- 27678095 TI - Investigating the Role of Fetal Gene Expression in Preterm Birth. AB - Second-trimester amniotic fluid supernatant (AFS) contains cell-free fetal RNA (cffRNA) transcripts that can provide information about fetal gene expression. In a retrospective case-control study, we measured second-trimester fetal gene expression using cffRNA extracted from AFS in women who had spontaneous preterm birth (sPTB) <34 weeks and in women who delivered >37 weeks. We extracted cffRNA from AFS of women with singletons who had second-trimester genetic amniocenteses. Twenty-one gravidas who had sPTB and 21 term controls were matched 1:1 for maternal age, fetal sex, race, gestational age (GA) at the time of amniocentesis, and medication exposure. Cell-free fetal RNA was extracted and hybridized to a customized 65-gene NanoString panel containing genes related to oxidative stress, inflammation, and hypothalamic-pituitary-adrenal (HPA) axis and included 15 housekeeping genes. Two models were run, 1 examining sPTB in relation to case/control status and 1 examining sPTB in relation to GA as a continuous variable. Among cases, the gene expression of nitric oxide synthase 1 ( NOS1), d aspartate oxidase ( DDO), and Beta-2-microglobulin ( B2M) was higher than controls ( P value < .05; false discovery rate-corrected Q value of <=0.10). Nitric oxide synthase 1 and DDO are genes associated with oxidative stress; B2M is a marker of the fetal inflammatory response. Fetal HPA gene expression is not associated with GA at delivery or sPTB in second-trimester AFS. Alterations of fetal gene expression related to inflammation and oxidative stress antedate clinical symptoms and may be useful for early identification of patients at risk of having an sPTB. PMID- 27678096 TI - Twin Conception in Sheep Leads to Impaired Insulin Sensitivity and Sexually Dimorphic Adipose Tissue and Skeletal Muscle Phenotypes in Adulthood. AB - Twins are often born small and early and have increased risk of obesity and diabetes later in life. Twin conception in sheep, regardless of whether the pregnancy continues as twins or is reduced to singleton in early gestation, alters offspring growth trajectory and body composition in young adulthood. We hypothesized that twin conception would result in insulin resistance in adulthood, with insulin-resistant adipose tissue and skeletal muscle phenotypes. At 3 years of age, body weight was not different among singletons, twins, and reductions; females weighed less than males. Singletons were leaner than reductions, with twins intermediate. Twins and reductions had decreased insulin sensitivity compared with singletons (singletons: mean [standard error of the mean]: 4.75 [0.4], twins: 3.34 [0.3], reductions: 3.67 [0.2] mg.I MUU-1.kg-1.min 1, P < .01). There were no group differences in adipocyte size, adipose tissue, or circulating tumor necrosis factor alpha, monocyte chemoattractant protein 1, or interleukin 6 concentrations. In males, omental and subcutaneous adipose SLC2A4 was 1.5- to 2.0-fold greater in twins and reductions than in singletons ( P < .01) and SLC2A1 was greater in reductions than in singletons. Skeletal muscle IRS-1 was decreased in male twins but increased in female twins, compared to singletons ( P <= .01), with no effect on reductions in either sex. Skeletal muscle SLC2A4 was decreased in female twins and reductions but elevated in male twins and reductions compared to singletons ( P <= .01). We conclude that adult twin insulin resistance is not due to adipose tissue phenotype, but potentially phenotypic effects in skeletal muscle, and obesity is a result of twin conception per se with its origins in early gestation. PMID- 27678097 TI - New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction. AB - The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11+0 to 13+6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11+0 to 13+6 gestational weeks) of early-onset preeclampsia with FGR. PMID- 27678099 TI - Efficacy, Safety, and Acceptability of Low-Dose Mifepristone and Self Administered Misoprostol for Ultra-Early Medical Abortion: A Randomized Controlled Trial. AB - The aim of this study was to investigate the efficacy, safety, and acceptability of low-dose mifepristone combined with self-administered misoprostol for ultra early medical abortion. A total of 744 women with ultra-early pregnancy (amenorrhea <=35 days) who fulfilled the inclusion criteria were enrolled in the study. Equal numbers of participants were allocated randomly to the hospital administration and self-administration groups. All participants took 75 mg mifepristone at the initial visit and 400 ug oral misoprostol 24 hours later in the hospital or by self-administration. The primary end point was complete abortion. Secondary end points were rates of unscheduled reattendance, time required for and cost of hospital observation and follow-up, vaginal bleeding, adverse effects, menstrual disturbance in the posttreatment period, and satisfaction rating. No differences in the rates of complete abortion, unscheduled reattendance, vaginal bleeding, adverse effects, or return of posttreatment menstruation were observed. The time required for (and costs of) hospital observation and follow-up per participant was 557.82 minutes (and US$40.12) in the hospital administration group and 18.46 minutes (and US$1.96) in the self-administration group (both P < .001). Satisfaction rates were similar in both groups, but the rates of "very satisfied" responses (87.60% vs 25.41%) and follow-up compliance (loss to follow-up, 0.45% vs 7.70%) were higher in the self administration group (both P < .001). Low-dose mifepristone combined with self administered misoprostol for ultra-early pregnancy termination was as effective and safe as hospital administration, with greater acceptability and lower cost to the women. PMID- 27678098 TI - Impact of Endometrioma Resection on Eutopic Endometrium Metabolite Contents: Noninvasive Evaluation of Endometrium Receptivity. AB - The aim of this study was to determine whether endometrioma resection alters most commonly defined endometrial metabolites, lactate (Lac), N-acetylaspartate (NAA), creatine 1 (Cr1), creatine 2 (Cr2), and choline (Cho) during the window of implantation. Twenty patients with uni- or bilateral endometrioma and 7 patients having nonendometriotic benign ovarian cyst were included. Midluteal phase magnetic resonance spectroscopy analysis of eutopic endometrium was performed before surgery. Second spectrum of endometrium was obtained 3 to 5 months after laparoscopic endometrioma resection. Pre- and postoperative endometrial peaks of Lac, NAA, Cr, and Cho were measured in units and denominated in parts per million (ppm). Compared to preoperative peak values, significantly decreased NAA, Lac, and Cr1 signals were noted in patients undergoing endometrioma surgery. Nearly 5 fold decline in the NAA signal occurred after endometrioma surgery (1.94 +/- 3.24 vs 0.37 +/- 0.55). Likewise, 2.5-fold decline in Lac signals was noted after endometrioma resection (2.81 +/- 2.64 vs 1.06 +/- 1.88). Both uni- and bilateral endometrioma affected endometrium signals the same. The peak intensity of Cho, Cr1, Cr2, NAA, and Lac did not alter significantly after nonendometriotic cyst surgery. Endometrioma surgery straightens endometrial NAA, Lac, and Cr1 peaks, suggesting improvement in endometrial receptivity. PMID- 27678100 TI - Serum Osteopontin Levels Are Decreased in Focal Adenomyosis. AB - We investigated whether serum osteopontin (OPN) levels are different according to specific phenotypes of adenomyosis and endometriosis. We conducted a prospective laboratory study in a university referral center for endometriosis between May 2005 and May 2013 and included 148 nonpregnant women, younger than 42 years, undergoing surgery for a benign gynecological condition and who had a preoperative pelvic magnetic resonance imaging (MRI). The presence of focal and/or diffuse adenomyosis was determined by pelvic MRI, and women were classified into 3 groups: no-adenomyosis (No-AM), isolated diffuse adenomyosis (DIF-AM), and focal adenomyosis with or without diffuse adenomyosis (FOC-AM). After complete surgical exploration of the pelvic cavity, the presence and type of endometriosis was surgically determined and histologically confirmed. We distinguished 4 phenotypes: no endometriosis, superficial peritoneal endometriosis (SUP), ovarian endometrioma, and deep infiltrating endometriosis (DIE). Osteopontin levels were measured by enzyme-linked immunosorbent assay in serum samples obtained in all participants in the month preceding surgery. Our results show lower OPN levels in women with focal adenomyosis compared to adenomyosis-free controls. Our results also show a decrease in OPN levels in women with associated DIE and focal adenomyosis compared to women with SUP. Various serum biomarkers have been studied in the context of endometriosis severity and subtypes, whereas data on serum markers of adenomyosis are scarce. Both entities are often associated, and adenomyosis could be a confounding factor influencing results. Future research on serum biomarkers should describe subtypes of adenomyosis and endometriosis and analyze results according to well-defined subtypes. PMID- 27678101 TI - Toward Understanding Myometrial Regulation: Metabolomic Investigation Reveals New Pathways of Oxytocin and Ritodrine Activity on the Myometrium. AB - In recent times, additional pathways involved in the regulation of the myometrium have been suggested. This also holds true for the effect of drugs such as oxytocin (OT) and beta-adrenergic agonists on the myometrium. Knowledge of these additional pathways will certainly prove useful in designing better therapies for pathologies of the myometrium. This study was therefore aimed at investigating the possibility of other pathways involved in the activities of both OT and ritodrine (RIT; a beta-adrenergic agonist) in the myometrium by utilizing metabolomics and bioinformatics. High-resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy coupled with functional uterine assays were used for an innovative assessment. In vitro pharmacological assay of OT (1 nmol/L) and RIT (0.1 nmol/L) on isolated mice uteri mounted in 3 mL organ baths was performed. Mice uteri, treated with OT or RIT, as well as the physiological buffer in which the uterine tissues were immersed, were rapidly collected and analyzed using HRFTMS, proton (1H)-NMR, and bioinformatics. Resulting data were analyzed via pairwise chemometric comparison models, with P <= .05 considered statistically significant. In addition to previously known metabolites, nicotinamide adenine dinucleotide, gamma aminobutyric acid, and sphingosine were significantly associated with the activity of OT, whereas the activity of RIT was associated with a downstream involvement of prostaglandin F1 and phosphatidylinositol signaling. These findings add evidence to the reports on additional regulation of myometrial activity by these drugs and suggest newer pathways for therapeutic manipulation. PMID- 27678102 TI - Variable Methylation Potential in Preterm Placenta: Implication for Epigenetic Programming of the Offspring. AB - Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions. Our previous studies in women delivering preterm show altered plasma levels of micronutrients and lower plasma LCPUFA levels. We postulate that alterations in the micronutrient metabolism may affect the regulation of enzymes, methionine adenosyltransferase ( MAT2A), and SAH-hydrolase ( AHCY), involved in the production of methyl donor S adenosylmethionine (SAM), thereby influencing the methylation potential (MP) in the placenta of women delivering preterm. The present study, therefore, examines the mRNA, protein levels of enzymes ( MAT2A and AHCY), SAM, S adenosylhomocysteine (SAH) levels, and global DNA methylation levels from preterm (n = 73) and term (n = 73) placentae. The enzyme messenger RNA (mRNA) levels were analyzed by real-time quantitative polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay, and SAM-SAH levels by high-performance liquid chromatography. The mRNA levels for MAT2A and AHCY are higher ( P < .05 for both) in the preterm group as compared to the term group. S-Adenosylmethionine and SAH levels were similar in both groups, although SAM:SAH ratio was lower ( P < .05) in the preterm group as compared to the term group. The global DNA methylation levels were higher ( P < .05) in women delivering small for gestation age infants as compared to women delivering appropriate for gestation age infants at term. Our data showing lower MP in the preterm placenta may have implications for the epigenetic programming of the developing fetus. PMID- 27678105 TI - Authors' response to Ghatak and Gulati. PMID- 27678104 TI - Erratum to:Hepatic resection for predominantly large size hepatocellular carcinoma: Early and long-term results from a tertiary care center in India. PMID- 27678103 TI - Long-term outcomes of children treated for Cushing's disease: a single center experience. AB - PURPOSE: Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. METHODS: Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). RESULTS: Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. CONCLUSIONS: The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects. PMID- 27678106 TI - Feasibility of ferumoxytol-enhanced neonatal and young infant cardiac MRI without general anesthesia. AB - PURPOSE: To assess the feasibility of ferumoxytol-enhanced anesthesia-free cardiac MRI in neonates and young infants for complex congenital heart disease (CHD). MATERIALS AND METHODS: With Institutional Review Board approval, 21 consecutive neonates and young infants (1 day to 11 weeks old; median age of 3 days) who underwent a rapid two-sequence (MR angiography [MRA] and four dimensional [4D] flow) MRI protocol with intravenous ferumoxytol without sedation (n = 17) or light sedation (n = 4) at 3 Tesla (T) (except one case at 1.5T) between June 2014 and February 2016 were retrospectively identified. Medical records were reviewed for indication, any complications, if further diagnostic imaging was performed after MRI, and surgical findings. Two radiologists scored the images in two sessions on a 5-point scale for overall image quality and delineation of various anatomical structures. Confidence interval of proportions for likelihood of requiring additional diagnostic imaging after MRI was determined. For the possibility of reducing the protocol to a single rapid sequence, Wilcoxon-rank sum test was used to assess whether 4D flow and MRA significantly differed in anatomical delineation. RESULTS: One of 21 patients (4.8%, 80% confidence interval 0-11%) required additional imaging, a computed tomography angiography to assess lung parenchyma and peripheral pulmonary arteries. Only 1 of 13 patients (7.7%) with operative confirmation had a minor discrepancy between radiology and operative reports (80% confidence interval 0 17%). 4D flow was significantly superior to MRA (P < 0.05) for the evaluation of systemic arteries, valves, ventricular trabeculae, and overall quality. Using Cohen's kappa coefficient, there was good interobserver agreement for the evaluation of systemic arteries by 4D flow (kappa = 0.782), and systemic veins and pulmonary arteries by MRA (kappa > 0.6). Overall 4D flow measurements (mean kappa = 0.64-0.74) had better internal agreement compared with MRA (mean kappa = 0.30-0.64). CONCLUSION: Ferumoxytol-enhanced cardiac MRI, without anesthesia, is feasible for the evaluation of complex CHD in neonates and young infants, with a low likelihood of need for additional diagnostic studies. The decreased risk by avoiding anesthesia must be balanced against the potential for adverse reactions with ferumoxytol. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1407-1418. PMID- 27678107 TI - Functional organization of the HIV lipid envelope. AB - The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes. By combining two-photon excited Laurdan fluorescence imaging and atomic force microscopy, we have obtained unprecedented insights into the phase state of membranes reconstituted from viral lipids (i.e., extracted from infectious HIV-1 particles), established the role played by the different specimens in the mixtures, and characterized the effects of membrane-active virucidal agents on membrane organization. In determining the molecular basis underlying lipid packing and lateral heterogeneity of the HIV-1 membrane, our results may help develop compounds with antiviral activity acting by perturbing the functional organization of the lipid envelope. PMID- 27678108 TI - The role of global public health strategy in non-profit organisational change at country level: lessons from the joining of Save the Children and Merlin in Myanmar. AB - INTRODUCTION: The paper presents a case study that critically assesses the role of global strategy 'Public Health on the Frontline 2014-2015' ('the Strategy') in supporting Merlin and Save the Children's organisational change and future programme of the combined organisation in Myanmar. MATERIALS AND METHODS: Research was undertaken in 2014 in Myanmar. Twenty-six individual and three group interviews were conducted with stakeholders, and 10 meetings relevant to the country organisational transition process were observed. A conceptual framework was developed to assess the role of the global strategy in supporting the country change process. RESULTS: Several positive aspects of the global strategy were found, as well as critical shortcomings in its support to the organisational change process at country level. The strategy was useful in signalling Save the Children's intention to scale up humanitarian health provision. However, it had only limited influence on the early change process and outcomes in Myanmar. CONCLUSIONS: Results highlight several aspects that would enhance the role of a global strategy at country level. Lessons can be applied by organisations undertaking a similar process. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27678110 TI - Parenting and cognitive and psychomotor delay due to small-for-gestational-age birth. AB - BACKGROUND: To examine whether different dimensions of parenting at different ages help small-for-gestational-age (SGA) children 'catch-up' the normal children in cognition and psychomotor. METHODS: We analyzed data of 800 children born SGA and 3,000 children born appropriate-for-gestational-age (AGA) from the Early Childhood Longitudinal Study-Birth cohort. The Two Bag Task was used to measure 2 year or 4-year parenting dimensions. Children's reading, math, gross motor, and fine motor scores were assessed at 5 years. Multivariable linear regression models were fitted to test the interactions between SGA and 2-year or 4-year parenting dimensions on 5-year cognitive and psychomotor outcomes (dependent variables). RESULTS: There were significant interactions between SGA and early parenting on 5-year reading, math, and fine motor scores. The gap between SGA and AGA children in 5-year fine motor score was attenuated to null [-0.25 (95% confidence interval, -0.41, -0.09) vs. 0.03 (-0.13, 0.20)] when 2-year parental sensitivity score increased from 1 standard deviation (SD) below mean (Mean - SD) to 1 SD above mean (Mean + SD). The gap between SGA and AGA children in 5-year fine motor [-0.28 (-0.44, -0.13) vs. 0.06 (-0.09, 0.22)] and math [-1.32 (-2.27, 0.37) vs. 0.20 (-0.77, 1.17)] scores was also attenuated to null when 4-year parental emotional support score increased from Mean - SD to Mean + SD. In contrast, the gap between SGA and AGA children in 5-year reading score increased from 0.49 (-0.90, 1.88) to -1.31 (-2.55, -0.07) when 4-year parental intrusiveness score increased from Mean - SD to Mean + SD. Similarly, the gap between SGA and AGA children in fine motor score increased with 4-year parental negative regard from 0.02 (-0.14, 0.18) to -0.23 (-0.38, -0.08). CONCLUSIONS: Early high-quality parenting may buffer some adversity in long-term reading, math, and fine motor skills related to SGA birth, whereas low-quality parenting can amplify the adversity. PMID- 27678111 TI - Bridging the Gap Between Adolescence and Adulthood: the Challenges of Emerging Adults. PMID- 27678109 TI - Annual direct and indirect costs attributable to nocturia in Germany, Sweden, and the UK. AB - OBJECTIVE: Our aim was to estimate the prevalence-based cost of illness imposed by nocturia (>=2 nocturnal voids per night) in Germany, Sweden, and the UK in an average year. METHODS: Information obtained from a systematic review of published literature and clinicians was used to construct an algorithm depicting the management of nocturia in these three countries. This enabled an estimation of (1) annual levels of healthcare resource use, (2) annual cost of healthcare resource use, and (3) annual societal cost arising from presenteeism and absenteeism attributable to nocturia in each country. RESULTS: In an average year, there are an estimated 12.5, 1.2, and 8.6 million patients >=20 years of age with nocturia in Germany, Sweden, and the UK, respectively. In an average year in each country, respectively, these patients were estimated to have 13.8, 1.4, and 10.0 million visits to a family practitioner or specialist, ~91,000, 9000, and 63,000 hospital admissions attributable to nocturia and 216,000, 19,000, and 130,000 subjects were estimated to incur a fracture resulting from nocturia. The annual direct cost of healthcare resource use attributable to managing nocturia was estimated to be approximately ?2.32 billion in Germany, 5.11 billion kr (?0.54 billion) in Sweden, and L1.35 billion (?1.77 billion) in the UK. The annual indirect societal cost arising from both presenteeism and absenteeism was estimated to be approximately ?20.76 billion in Germany and 19.65 billion kr (?2.10 billion) in Sweden. In addition, in the UK, the annual indirect cost due to absenteeism was an estimated L4.32 billion (?5.64 billion). CONCLUSIONS: Nocturia appears to impose a substantial socioeconomic burden in all three countries. Clinical and economic benefits could accrue from an increased awareness of the impact that nocturia imposes on patients, health services, and society as a whole. PMID- 27678112 TI - Tumor proliferation and diffusion on percolation clusters. AB - We study in silico the influence of host tissue inhomogeneity on tumor cell proliferation and diffusion by simulating the mobility of a tumor on percolation clusters with different homogeneities of surrounding tissues. The proliferation and diffusion of a tumor in an inhomogeneous tissue could be characterized in the framework of the percolation theory, which displays similar thresholds (0.54, 0.44, and 0.37, respectively) for tumor proliferation and diffusion in three kinds of lattices with 4, 6, and 8 connecting near neighbors. Our study reveals the existence of a critical transition concerning the survival and diffusion of tumor cells with leaping metastatic diffusion movement in the host tissues. Tumor cells usually flow in the direction of greater pressure variation during their diffusing and infiltrating to a further location in the host tissue. Some specific sites suitable for tumor invasion were observed on the percolation cluster and around these specific sites a tumor can develop into scattered tumors linked by some advantage tunnels that facilitate tumor invasion. We also investigate the manner that tissue inhomogeneity surrounding a tumor may influence the velocity of tumor diffusion and invasion. Our simulation suggested that invasion of a tumor is controlled by the homogeneity of the tumor microenvironment, which is basically consistent with the experimental report by Riching et al. as well as our clinical observation of medical imaging. Both simulation and clinical observation proved that tumor diffusion and invasion into the surrounding host tissue is positively correlated with the homogeneity of the tissue. PMID- 27678113 TI - Identification of substituent groups and related genes involved in salecan biosynthesis in Agrobacterium sp. ZX09. AB - Salecan, a soluble beta-1,3-D-glucan produced by a salt-tolerant strain Agrobacterium sp. ZX09, has been the subject of considerable interest in recent years because of its multiple bioactivities and unusual rheological properties in solution. In this study, both succinyl and pyruvyl substituent groups on salecan were identified by an enzymatic hydrolysis following nuclear magnetic resonance (NMR), HPLC, and MS analysis. The putative succinyltransferase gene (sleA) and pyruvyltransferase gene (sleV) were determined and cloned. Disruption of the sleA gene resulted in the absence of succinyl substituent groups on salecan. This defect could be complemented by expressing the sleA cloned in a plasmid. Thus, the sleA and sleV genes located in a 19.6-kb gene cluster may be involved in salecan biosynthesis. Despite the lack of succinyl substituents, the molecular mass of salecan generated by the sleA mutant did not substantially differ from that generated by the wild-type strain. Loss of succinyl substituents on salecan changed its rheological characteristics, especially a decrease in intrinsic viscosity. PMID- 27678114 TI - Degradation of 3-phenoxybenzoic acid by a filamentous fungus Aspergillus oryzae M 4 strain with self-protection transformation. AB - A novel filamentous fungus M-4 strain was isolated from soy sauce koji and identified as Aspergillus oryzae (Collection number: CGMCC 11645) on the basis of morphological characteristics and internal transcribed spacer sequence. M-4 could degrade 80.62 % of 3-phenoxybenzoic acid (3-PBA; 100 mg L-1) within 5 days. 3-PBA degradation occurred in accordance with first-order kinetics. The degradation metabolites of 3-PBA were identified through high-performance liquid chromatography-mass spectrometry (HPLC-MS). Relevant enzymatic activities and substrate utilization were also investigated, which indicated that M-4 could effectively degrade the intermediates of 3-PBA. Base on analysis of these metabolites, a novel biochemical pathway for the degradation of 3-PBA was proposed. There exists a mutual transformation between 3-phenoxy-benzyl alcohol and 3-PBA, which was firstly reported about the degradation of 3-PBA and may be attributed to self-protection transformation of M-4; subsequently, 3-PBA was gradually transformed into phenol, 3-hydroxy-5-phenoxy benzoic acid, protocatechuic acid and gallic acid. The safety of M-4 was evaluated via an acute toxicity test in vivo. The biodegradation ability of M-4 without toxic effects reveals that this fungus may be likely to be used for eliminating 3-PBA from contaminated environment or fermented foods. PMID- 27678115 TI - Eliminating hydrolytic activity without affecting the transglycosylation of a GH1 beta-glucosidase. AB - Unveiling the determinants for transferase and hydrolase activity in glycoside hydrolases would allow using their vast diversity for creating novel transglycosylases, thereby unlocking an extensive toolbox for carbohydrate chemists. Three different amino acid substitutions at position 220 of a GH1 beta glucosidase from Thermotoga neapolitana caused an increase of the ratio of transglycosylation to hydrolysis (r s/r h) from 0.33 to 1.45-2.71. Further increase in r s/r h was achieved by modulation of pH of the reaction medium. The wild-type enzyme had a pH optimum for both hydrolysis and transglycosylation around 6 and reduced activity at higher pH. Interestingly, the mutants had constant transglycosylation activity over a broad pH range (5-10), while the hydrolytic activity was largely eliminated at pH 10. The results demonstrate that a combination of protein engineering and medium engineering can be used to eliminate the hydrolytic activity without affecting the transglycosylation activity of a glycoside hydrolase. The underlying factors for this success are pursued, and perturbations of the catalytic acid/base in combination with flexibility are shown to be important factors. PMID- 27678116 TI - Cellulose synthesis by Komagataeibacter rhaeticus strain P 1463 isolated from Kombucha. AB - Isolate B17 from Kombucha was estimated to be an efficient producer of bacterial cellulose (BC). The isolate was deposited under the number P 1463 and identified as Komagataeibacter rhaeticus by comparing a generated amplified fragment length polymorphism (AFLPTM) DNA fingerprint against a reference database. Static cultivation of the K. rhaeticus strain P 1463 in Hestrin and Schramm (HS) medium resulted in 4.40 +/- 0.22 g/L BC being produced, corresponding to a BC yield from glucose of 25.30 +/- 1.78 %, when the inoculum was made with a modified HS medium containing 10 g/L glucose. Fermentations for 5 days using media containing apple juice with analogous carbon source concentrations resulted in 4.77 +/- 0.24 g/L BC being synthesised, corresponding to a yield from the consumed sugars (glucose, fructose and sucrose) of 37.00 +/- 2.61 %. The capacity of K. rhaeticus strain P 1463 to synthesise BC was found to be much higher than that of two reference strains for cellulose production, Komagataeibacter xylinus DSM 46604 and Komagataeibacter hansenii DSM 5602T, and was also considerably higher than that of K. hansenii strain B22, isolated from another Kombucha sample. The BC synthesised by K. rhaeticus strain P 1463 after 40 days of cultivation in HS medium with additional glucose supplemented to the cell culture during cultivation was shown to have a degree of polymerization of 3300.0 +/- 122.1 glucose units, a tensile strength of 65.50 +/- 3.27 MPa and a length at break of 16.50 +/- 0.83 km. For the other strains, these properties did not exceed 25.60 +/- 1.28 MPa and 15.20 +/- 0.76 km. PMID- 27678117 TI - Metabolic engineering of the oleaginous yeast Rhodosporidium toruloides IFO0880 for lipid overproduction during high-density fermentation. AB - Natural lipids can be used to make biodiesel and many other value-added compounds. In this work, we explored a number of different metabolic engineering strategies for increasing lipid production in the oleaginous yeast Rhodosporidium toruloides IFO0880. These included increasing the expression of enzymes involved in different aspects of lipid biosynthesis-malic enzyme (ME), pyruvate carboxylase (PYC1), glycerol-3-P dehydrogenase (GPD), and stearoyl-CoA desaturase (SCD)-and deleting the gene PEX10, required for peroxisome biogenesis. Only malic enzyme and stearoyl-CoA desaturase, when overexpressed, were found to significantly increase lipid production. Only stearoyl-CoA desaturase, when overexpressed, further increased lipid production in a strain previously engineered to overexpress acetyl-CoA carboxylase (ACC1) and diacylglycerol acyltransferase (DGA1). Our best strain produced 27.4 g/L lipid with an average productivity of 0.31 g/L/h during batch growth on glucose and 89.4 g/L lipid with an average productivity of 0.61 g/L/h during fed-batch growth on glucose. These results further establish R. toruloides as a platform organism for the production of lipids and potentially other lipid-derived compounds from sugars. PMID- 27678118 TI - Genetic analyses of Per.C6 cell clones producing a therapeutic monoclonal antibody regarding productivity and long-term stability. AB - Genetic characterization of protein-producing clones represents additional value to cell line development. In the present study, ten Per.C6 clones producing a Rebmab100 monoclonal antibody were selected using two cloning methods: six clones originated from limiting dilution cloning and four by the automated colony picker ClonePix FL. A stability program was performed for 50 generations, including 4 batches distributed along the timeframe to determine specific productivity (Qp) maintenance. Four stable clones (two from limiting dilution and two from ClonePix FL) were further evaluated. The relative mRNA expression levels of both heavy chain (HC) and light chain (LC) genes were verified at generations 0, 30-35, and 50-55 of the stability program. At generations 0 and 30-35, LC gene expression level was higher than HC gene, whereas at generation 50-55, the opposite prevailed. A high correlation was observed between Qp and HC or LC mRNA expression level for all clones at each generation analyzed along the continuous culture. The mRNA stability study was performed at steady-state culture. The LC gene displayed a higher half-life and lower decay constant than HC gene, accounting for the higher observed expression level of LC mRNA in comparison to HC mRNA. Clone R6 was highlighted due its high Qp, mRNA expression levels, and mRNA stability. Besides the benefits of applying genetic characterization for the selection of stable and high-producing clones, the present study shows for the first time the correlation between Qp and HC or LC expression levels and also mRNA stability in clones derived from human cell line Per.C6((r)). PMID- 27678120 TI - Bacterial glucans: production, properties, and applications. AB - Bacterial glucans have aroused increasing interest in commercial applications in the food and pharmaceutical sectors. A number of bacterial glucans have been reported over recent decades, and their structure, production, and functional properties have been extensively studied. In this paper, we review recent researches on bacterial glucans, with emphasis on the production, physical and chemical properties, and the new developments in food, biomedical, pharmaceutical, and other industrial applications. PMID- 27678119 TI - Characteristics and metabolic pathway of Alcaligenes sp. TB for simultaneous heterotrophic nitrification-aerobic denitrification. AB - A novel heterotrophic nitrification-aerobic denitrification bacterium, Alcaligenes sp. TB (GenBank accession no. JQ044686), was isolated from a rotating drum biofilter for NO removal. Its characteristics and metabolic pathway for NO removal were comprehensively investigated. Experimental results showed that the nitrification and denitrification efficiency reached 99.42 and 96.44 %, respectively, after 44 h under the conditions of pH 7.2, 30 degrees C, and 120 rpm. The tests with the addition of Pb2+ and Na2WO4 as the reductase inhibitor revealed that nitrite was the key intermediate to produce the nitrogen gas as the final product in the simultaneous heterotrophic nitrification and denitrification by strain TB. Based on the experimental results, the metabolic pathway of strain TB has been proposed that it carries out shortcut/complete simultaneous nitrification and denitrification with nitrite as an intermediate and nitrogen gas as a final product. The two potential metabolic pathways existing in strain TB can be described as NH4+ -> NH2OH -> NO2- -> N2O -> N2 and NH4+ -> NH2OH -> NO2- -> NO3- -> NO2- -> N2O -> N2. This work indicates that the strain TB may be a good candidate for the denitrification of the sewage. PMID- 27678121 TI - Atopic Dermatitis Susceptibility Variants in Filaggrin Hitchhike Hornerin Selective Sweep. AB - Human skin has evolved rapidly, leaving evolutionary signatures in the genome. The filaggrin (FLG) gene is widely studied for its skin-barrier function in humans. The extensive genetic variation in this gene, especially common loss-of function (LoF) mutations, has been established as primary risk factors for atopic dermatitis. To investigate the evolution of this gene, we analyzed 2,504 human genomes and genotyped the copy number variation of filaggrin repeats within FLG in 126 individuals from diverse ancestral backgrounds. We were unable to replicate a recent study claiming that LoF of FLG is adaptive in northern latitudes with lower ultraviolet light exposure. Instead, we present multiple lines of evidence suggesting that FLG genetic variation, including LoF variants, have little or no effect on fitness in modern humans. Haplotype-level scrutinization of the locus revealed signatures of a recent selective sweep in Asia, which increased the allele frequency of a haplotype group (Huxian haplogroup) in Asian populations. Functionally, we found that the Huxian haplogroup carries dozens of functional variants in FLG and hornerin (HRNR) genes, including those that are associated with atopic dermatitis susceptibility, HRNR expression levels and microbiome diversity on the skin. Our results suggest that the target of the adaptive sweep is HRNR gene function, and the functional FLG variants that involve susceptibility to atopic dermatitis, seem to hitchhike the selective sweep on HRNR. Our study presents a novel case of a locus that harbors clinically relevant common genetic variation with complex evolutionary trajectories. PMID- 27678122 TI - The Impact of Linked Selection in Chimpanzees: A Comparative Study. AB - Levels of nucleotide diversity vary greatly across the genomes of most species owing to multiple factors. These include variation in the underlying mutation rates, as well as the effects of both direct and linked selection. Fundamental to interpreting the relative importance of these forces is the common observation of a strong positive correlation between nucleotide diversity and recombination rate. While indeed observed in humans, the interpretation of this pattern has been difficult in the absence of high-quality polymorphism data and recombination maps in closely related species. Here, we characterize genetic features driving nucleotide diversity in Western chimpanzees using a recently generated whole genome polymorphism data set. Our results suggest that recombination rate is the primary predictor of nucleotide variation with a strongly positive correlation. In addition, telomeric distance, regional GC-content, and regional CpG-island content are strongly negatively correlated with variation. These results are compared with humans, with both similarities and differences interpreted in the light of the estimated effective population sizes of the two species as well as their strongly differing recent demographic histories. PMID- 27678123 TI - Comparative Genome Analysis of the Daptomycin-Resistant Streptococcus anginosus Strain J4206 Associated with Breakthrough Bacteremia. AB - Streptococcus anginosus is a member of the normal oral flora that can become a pathogen causing pyogenic infections in humans. The genome of daptomycin resistant strain J4206, originally isolated from a patient suffering from breakthrough bacteremia and septic shock at the University of Texas Health Science Center at San Antonio, was determined. The circular genome is 2,001,352 bp long with a GC content of 38.62% and contains multiple mobile genetic elements, including the phage-like chromosomal island SanCI that mediates a mutator phenotype, transposons, and integrative conjugative elements. Daptomycin resistance involves multiple alterations in the cell membrane and cell wall, and unique features were identified in J4206 that may contribute to resistance. A cluster of capsular polysaccharide (CPS) genes for choline metabolism and transport are present that may help neutralize cell surface charges, destabilizing daptomycin binding. Further, unique J4206 genes encoding sortases and LPXTG-target proteins that are involved in cell wall modification were present. The J4206 genome is phylogenetically closely related to the recently reported vancomycin-resistant SA1 strain; however, these genomes differ with SNPs in cardiolipin synthetase, histidine kinase yycG, teichoic acid modification genes, and other genes involved in cell surface modification. Transmission electron microscopy showed that the cell walls of both strains J4206 and SA1 were significantly thicker and more electron dense than daptomycin- and vancomycin sensitive strain J4211. This comparative genomic study has identified unique genes as well as allelic variants in the J4206 genome that are involved in cell surface modification and thus might contribute to the acquisition of daptomycin resistance. PMID- 27678124 TI - Bone Loss Among Women Living With HIV. AB - Clinical data accumulated over the past two decades attests to a significant decline in bone mineral density (BMD) in patients infected by HIV, which does not remit but may actually intensify with anti-retroviral therapy (ART). Long generally perceived as an aberration without clinical consequences in relatively young HIV-infected cohorts, recent studies have documented marked increases in fracture incidence in HIV-infected men and women over a wide age continuum. Fractures are associated with chronic pain, crippling morbidity, and increased mortality, undermining the gains in quality of life achieved though ART. As bone loss and resulting increases in fracture incidence are a natural consequence of aging, there is now concern regarding the long-term consequences of HIV/ART associated premature bone loss, given the transition of the HIV/AIDS population into an older age demographic. The development of guidelines for diagnosis and treatment of bone disease within the context of HIV and ART has been an important recent step in raising awareness of the problem and the implications of bone fracture for patient health. Significant progress has also been made in recent years in dissecting the complex and multifactorial mechanisms driving bone loss in HIV/ART and the role of underlying immunological disruption in skeletal dysmorphogenesis. This review examines recent progress in the field and studies by Women's Interagency HIV Study (WIHS)-associated investigators, inside and outside of the WIHS cohort, aimed at identifying skeletal abnormalities, quantifying facture incidence, management, and understanding underlying mechanisms in people living with HIV in the context of chronic ART. PMID- 27678125 TI - Lake sedimentary DNA accurately records 20th Century introductions of exotic conifers in Scotland. AB - Sedimentary DNA (sedDNA) has recently emerged as a new proxy for reconstructing past vegetation, but its taphonomy, source area and representation biases need better assessment. We investigated how sedDNA in recent sediments of two small Scottish lakes reflects a major vegetation change, using well-documented 20th Century plantations of exotic conifers as an experimental system. We used next generation sequencing to barcode sedDNA retrieved from subrecent lake sediments. For comparison, pollen was analysed from the same samples. The sedDNA record contains 73 taxa (mainly genus or species), all but one of which are present in the study area. Pollen and sedDNA shared 35% of taxa, which partly reflects a difference in source area. More aquatic taxa were recorded in sedDNA, whereas taxa assumed to be of regional rather than local origin were recorded only as pollen. The chronology of the sediments and planting records are well aligned, and sedDNA of exotic conifers appears in high quantities with the establishment of plantations around the lakes. SedDNA recorded other changes in local vegetation that accompanied afforestation. There were no signs of DNA leaching in the sediments or DNA originating from pollen. PMID- 27678126 TI - Associations between job demands, work-related strain and perceived quality of care: a longitudinal study among hospital physicians. AB - Objective: Drawing on a sample of hospital physicians, we attempted to determine prospective associations between three job demands, work-related strain and perceived quality of care. Design: Longitudinal follow-up study with with a 1 year time lag. Setting: Physicians of two acute-care hospitals in Germany (one general urban and one children's hospital). Study participants: Ninety-five physicians filled out a standardized questionnaire. Main outcomes measures: Physicians' evaluations of quality of care at both waves. Results: Our results support the hypothesis that job demands directly influence quality of care irrespective of strain. Specifically, high social stressors (beta = -0.15, P = 0.036) and time pressure (beta = -0.19, P = 0.031) were associated with decreased quality of care over time. We additionally observed reversed effects from quality of care at baseline to time pressure at follow-up (beta = -0.35, P = 0.006). Contrary to expectations, physicians' work-related strain did not mediate the job demands-quality of care-relationship, nor were strain-to-stressor effects observed. Conclusions: Our results corroborate that hospital work environments with high demands have a direct impact on physician-perceived quality of care. In turn, poor care practices contribute to increased job demands. Our findings also emphasize that further understanding is required of how physicians' workplace conditions affect job demands, well-being, and quality of care, respectively. PMID- 27678127 TI - The influence of emergency department crowding on the efficiency of care for acute stroke patients. AB - Objective: To investigate the impact of emergency department (ED) crowding (number of ED patients) and number of ED staff on the efficiency of the ED care process for acute stroke patients. Design: Retrospective cohort study conducted from 1 May 2008 to 31 December 2013. Setting: Largest primary stroke center (3000 bed tertiary academic hospital) in southern Taiwan. Participants: Patients aged 18-80 years presenting to the ED with acute stroke symptoms <=3 h from symptom onset (n = 1142). Main Outcome Measures: Door-to-assessment time (DTA), door-to computed tomography completion time (DTCT) and door-to-needle time (DTN). Results: Of the 785 patients with ischemic stroke, 90 (11.46%) received thrombolysis. In the multivariate regression analysis, the number of ED patients and the number of attending physicians were significantly associated with delayed DTA and DTCT but not DTN. Initial assessment by a resident was also associated with delayed DTA and DTCT. The number of nurses was associated with delayed DTCT and DTN. Conclusions: Although ED crowding was not associated with delayed DTN, it predicted delayed DTA and DTCT in thrombolysis-eligible stroke patients. The number of attending physicians affected initial assessment and DTCTs, whereas the number of nurses impacted thrombolytic administration times. PMID- 27678128 TI - How different location modes influence responses in a Simon-like task. AB - Spatial information can be conveyed not only by stimulus position but by the meaning of a location word or direction of an arrow. We examined whether all the location-, arrow- and word-based Simon effects or some of them can be observed when a location word or an arrow is presented eccentrically and a left-right keypress is made to indicate its ink color. Results showed that only the location based Simon effect was observed for location words, whereas an additional smaller arrow-based Simon effect, compared to the location-based Simon effect was observed, for arrows. These results showed spatial location, arrow direction, and location word stimulus dimensions affect response position codes in a spatial-to verbal priority order, consistent with the possibility that they can activate mode-specific spatial representations. PMID- 27678129 TI - Unitization of route knowledge. AB - There are many theories that explain how route knowledge is acquired. We examined here if the sequence of elements that are part of a route can become integrated into a single unit, to the extent that the processing of individual transitions may only be relevant in the context of this entire unit. In Experiments 1 and 2, participants learned a route for ten blocks. Subsequently, at test they were intermittently exposed to the same training route along with a novel route which contained partial overlap with the original training route. Results show that the very same stimulus, appearing in the very same location, requiring the very same response (e.g., left turn), was responded to significantly faster in the context of the original training route than in the novel route. In Experiment 3, we employed a modified paradigm containing landmarks and two matched routes which were both substantially longer and contained a greater degree of overlap than the routes in Experiments 1 and 2. Results were replicated, namely, the same overlapping route segment, common to both routes, was performed significantly slower when appearing in the context of a novel than the original route. Furthermore, the difference between the overlapping segments was similar to the difference observed for the non-overlapping segments, i.e., an old route segment in the context of a novel route was processed as if it were an entirely novel segment. We discuss the results in relation to binding, chunking, and transfer effects, as well as potential practical implications. PMID- 27678130 TI - Divergent and Stereoselective Synthesis of beta-Silyl-alpha-Amino Acids through Palladium-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C-H Bonds. AB - A general and practical PdII -catalyzed intermolecular silylation of primary and secondary C-H bonds of alpha-amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure beta-silyl-alpha-amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration. The synthetic importance of this method is further demonstrated by the late-stage functionalization of biological small molecules, such as (-)-santonin and beta-cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this beta-C(sp3 )-H silylation process. PMID- 27678131 TI - Dual energy CT allows for improved characterization of response to antiangiogenic treatment in patients with metastatic renal cell cancer. AB - OBJECTIVES: To evaluate the potential role of dual energy CT (DECT) to visualize antiangiogenic treatment effects in patients with metastatic renal cell cancer (mRCC) while treated with tyrosine-kinase inhibitors (TKI). METHODS: 26 patients with mRCC underwent baseline and follow-up single-phase abdominal contrast enhanced DECT scans. Scans were performed immediately before and 10 weeks after start of treatment with TKI. Virtual non-enhanced (VNE) and colour coded iodine images were generated. 44 metastases were measured at the two time points. Hounsfield unit (HU) values for VNE and iodine density (ID) as well as iodine content (IC) in mg/ml of tissue were derived. These values were compared to the venous phase DECT density (CTD) of the lesions. Values before and after treatment were compared using a paired Student's t test. RESULTS: Between baseline and follow up, mean CTD and DECT-derived ID both showed a significant reduction (p < 0.005). The relative reduction measured in percent was significantly greater for ID than for CTD (49.8 +/- 36,3 % vs. 29.5 +/- 20.8 %, p < 0.005). IC was also significantly reduced under antiangiogenic treatment (p < 0.0001). CONCLUSIONS: Dual energy CT-based quantification of iodine content of mRCC metastases allows for significantly more sensitive and reproducible detection of antiangiogenic treatment effects. KEY POINTS: * A sign of tumour response to antiangiogenic treatment is reduced tumour perfusion. * DECT allows visualizing iodine uptake, which serves as a marker for vascularization. * More sensitive detection of antiangiogenic treatment effects in mRCC is possible. PMID- 27678132 TI - Contribution of mono-exponential, bi-exponential and stretched exponential model based diffusion-weighted MR imaging in the diagnosis and differentiation of uterine cervical carcinoma. AB - OBJECTIVES: To investigate the potential of various metrics derived from mono exponential model (MEM), bi-exponential model (BEM) and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in diagnosing and differentiating the pathological subtypes and grades of uterine cervical carcinoma. METHODS: 71 newly diagnosed patients with cervical carcinoma (50 cases of squamous cell carcinoma [SCC] and 21 cases of adenocarcinoma [AC]) and 32 healthy volunteers received DWI with multiple b values. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (alpha), and distributed diffusion coefficient (DDC) were calculated and compared between tumour and normal cervix, among different pathological subtypes and grades. RESULTS: All of the parameters were significantly lower in cervical carcinoma than normal cervical stroma except alpha. SCC showed lower ADC, D, f and DDC values and higher D* value than AC; D and DDC values of SCC and ADC and D values of AC were lower in the poorly differentiated group than those in the well moderately differentiated group. CONCLUSION: Compared with MEM, diffusion parameters from BEM and SEM may offer additional information in cervical carcinoma diagnosis, predicting pathological tumour subtypes and grades, while f and D showed promising significance. KEY POINTS: * DWI-derived parameters by different models are related but provide diversified information. * Commonly used ADC by MEM of DWI overestimates the tissue water diffusivity. * DWI processed by BEM could separate blood perfusion from true diffusion effects. * The derived diffusion-related and perfusion-related parameters by BEM are superior to ADC. PMID- 27678135 TI - Effects of dietary mixture of garlic (Allium sativum), coriander (Coriandrum sativum) and probiotics on immune responses and caecal counts in young laying hens. AB - This study was conducted to evaluate the effects of a combined mixture of phytogenic extracts (garlic and coriander) and probiotics on growth performance and immune responses in laying hens based on the results of in vitro studies to screen for immunomodulatory potency of each ingredient. Several parameters of immunomodulatory potency were estimated using lamina propria leucocytes (LPLs) isolated from rat intestinal mucosa tissue. Results show that the combined mixture enhanced LPLs proliferation, increased LPL-mediated cytotoxicity against YAC-1 tumour cells, and decreased lipopolysaccharide (LPS)-induced cytokine production including tumour necrosis factor-alpha (TNF-alpha) and interferon gamma (IFN-gamma) in LPLs. For in vivo study, laying hens (n = 50/each diet group) were fed with control diet, a diet containing antibiotics (0.01% per kg feed) or the combined mixture (0.02% per kg feed) for 21 days. The dietary combined mixture improved egg production (p < 0.05) but not growth performance and carcass traits. Interestingly, the patterns of suppressing plasma IFN-gamma productions during inflammation by LPS injection and decreasing caecal E. coli counts in the combined mixture group were comparable to those in the antibiotics group. Taken together, our results suggested that the 0.02% of combined mixture of phytogenic extracts and probiotics as ingredients has potential immunomodulatory effects in laying hens. PMID- 27678134 TI - Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery. AB - OBJECTIVES: To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. METHODS: Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. RESULTS: In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. CONCLUSIONS: Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. KEY POINTS: * Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. * Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. * Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to liver attenuation ratio. * Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. * Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma. PMID- 27678133 TI - The impact of clinically significant portal hypertension on the prognosis of patients with hepatocellular carcinoma after radiofrequency ablation: a propensity score matching analysis. AB - OBJECTIVES: To assess the impact of clinically significant portal hypertension (CSPH) on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). METHODS: We retrospectively enrolled 280 treatment-naive early-stage HCC patients who had Child-Pugh grade A or B and received upper gastrointestinal endoscopy at the time of HCC diagnosis. CSPH was defined as (1) a platelet count < 100,000/mm3 associated with splenomegaly and/or (2) the presence of oesophageal/gastric varices by endoscopy. Factors determining poor overall survival and recurrence after RFA were analysed by Cox proportional hazards model and propensity score matching analysis. RESULTS: A total of 192 (68.6 %) patients had CSPH. The cumulative 5-year survival rates were 50.6 % and 76.7 % in patients with and without CSPH, respectively (p = 0.015). Based on multivariate analysis, age > 65 years (hazard ratio (HR) 1.740, p = 0.025), serum albumin levels <= 3.5 g/dL (HR 3.268, p < 0.001) and multiple tumours (HR 1.693, p = 0.046), but not CSPH, were independent risk factors associated with poor overall survival after RFA. Moreover, the overall survival rates were comparable between patients with and without CSPH after adjusting for confounding factors via propensity score matching analysis. CONCLUSIONS: CSPH was not associated with poor outcomes after RFA. KEY POINTS: * CSPH was common in HCC patients who underwent RFA therapy. * CSPH was not an independent risk factor in determining poor prognosis. * Serum albumin level was more important to determine the outcomes. PMID- 27678136 TI - Carbon-Coated Porous Aluminum Foil Anode for High-Rate, Long-Term Cycling Stability, and High Energy Density Dual-Ion Batteries. AB - A 3D porous Al foil coated with a uniform carbon layer (pAl/C) is prepared and used as the anode and current collector in a dual-ion battery (DIB). The pAl/C graphite DIB demonstrates superior cycling stability and high rate performance, achieving a highly reversible capacity of 93 mAh g-1 after 1000 cycles at 2 C over the voltage range of 3.0-4.95 V. In addition, the DIB could achieve an energy density of ~204 Wh kg-1 at a high power density of 3084 W kg-1 . PMID- 27678137 TI - [Simulation-based training and OR apprenticeship for medical students : A prospective, randomized, single-blind study of clinical skills]. AB - BACKGROUND: Simulation-based training (SBT) has developed into an established method of medical training. Studies focusing on the education of medical students have used simulation as an evaluation tool for defined skills. A small number of studies provide evidence that SBT improves medical students' skills in the clinical setting. Moreover, they were strictly limited to a few areas, such as the diagnosis of heart murmurs or the correct application of cricoid pressure. Other studies could not prove adequate transferability from the skills gained in SBT to the patient site. Whether SBT has an effect on medical students' skills in anesthesiology in the clinical setting is controversial. To explore this issue, we designed a prospective, randomized, single-blind trial that was integrated into the undergraduate anesthesiology curriculum of our department during the second year of the clinical phase of medical school. OBJECTIVES: This study intended to explore the effect of SBT on medical students within the mandatory undergraduate anesthesiology curriculum of our department in the operating room with respect to basic skills in anesthesiology. MATERIALS AND METHODS: After obtaining ethical approval, the participating students of the third clinical semester were randomized into two groups: the SIM-OR group was trained by a 225 min long SBT in basic skills in anesthesiology before attending the operating room (OR) apprenticeship. The OR-SIM group was trained after the operating room apprenticeship by SBT. During SBT the students were trained in five clinical skills detailed below. Further, two clinical scenarios were simulated using a full-scale simulator. The students had to prepare the patient and perform induction of anesthesia, including bag-mask ventilation after induction in scenario 1 and rapid sequence induction in scenario 2. Using the five-point Likert scale, five defined skills were evaluated at defined time points during the study period. 1) application of the safety checklist, 2) application of basic patient monitoring, 3) establishment of intravenous access, 4) bag-and-mask ventilation, and 5) adjustment of ventilatory parameters after the patients' airways were secured. A cumulative score of 5 points was defined as the best and a cumulative score of 25 as the worst rating for a defined time point. The primary endpoint was the cumulative score after day 1 in the operating room apprenticeship and the difference in cumulative scores from days 1 to 4. Our hypothesis was that the SIM-OR group would achieve a better score after day 1 in the operating room apprenticeship and would gain a larger increase in score from day 1 to day 4 than the OR-SIM group. RESULTS: 73 students were allocated to the OR-SIM group and 70 students to the SIM-OR group. There was no significant difference between the two groups after day 1 of the operating room apprenticeship and no difference in increase of the cumulative score from day 1 to day 4 (median of cumulative score on day 1: 'SIM-OR' 11.2 points vs. 'OR-SIM' 14.6 points; p = 0.067; median of difference from day 1 to day 4: 'SIM-OR' -3.7 vs. 'OR-SIM' -6.4; p = 0.110). CONCLUSION: With the methods applied, this study could not prove that 225 min of SBT before the operating room apprenticeship increased the medical students' clinical skills as evaluated in the operating room. Secondary endpoints indicate that medical students have better clinical skills at the end of the entire curriculum when they have been trained through SBT before the operating room apprenticeship. However, the authors believe that simulator training has a positive impact on students' acquisition of procedural and patient safety skills, even if the methods applied in this study may not mirror this aspect sufficiently. PMID- 27678139 TI - Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2014-2016). AB - One of the most cited limitations of capillary (and microchip) electrophoresis is the poor sensitivity. This review continues to update this series of biennial reviews, first published in Electrophoresis in 2007, on developments in the field of on-line/in-line concentration methods in capillaries and microchips, covering the period July 2014-June 2016. It includes developments in the field of stacking, covering all methods from field amplified sample stacking and large volume sample stacking, through to isotachophoresis, dynamic pH junction, and sweeping. Attention is also given to on-line or in-line extraction methods that have been used for electrophoresis. PMID- 27678138 TI - Exploring the oviductal fluid proteome by a lectin-based affinity approach. AB - The analysis of glycoproteins in body fluids represents a central task in the study of vital processes. Herein, we assessed the combined use of Concanavalin A and Wheat Germ Agglutinin as ligands to fractionate and enrich glycoproteins from oviductal fluid (OF), which is a source of molecules involved in fertilization. First, the selectivity was corroborated by a gel-based approach using glycoprotein staining and enzymatic deglycosylation. Nanoliquid chromatography tandem mass spectrometry (nLC-ESI-MS/MS) further allowed the reliable identification of 134 nonbound as well as 130 lectin-bound OF proteins. Enrichment analysis revealed that 77% of the annotated proteins in the lectin bound fraction were known glycoproteins (p-value [FDR] = 1.45E-31). The low variance of the number of peptide spectrum matches for each protein within replicates indicated a consistent reproducibility of the whole workflow (median CV 17.3% for technical replicates and 20.7% for biological replicates). Taken together, this study highlights the applicability of a lectin-based workflow for the comprehensive analysis of OF proteins and gives for the first time an insight into the broad glycoprotein content of OF. PMID- 27678140 TI - Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage. AB - The CD4+CD25+ regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model. Tregs treatment reduced the content of pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, and malondialdehyde, while increasing the superoxide dismutase (SOD) enzymatic activity at day (1, 3 and 7) following ICH. Furthermore, Tregs treatment obviously reduced the number of NF-kappaB+, IL-6+, TUNEL+ and active caspase-3+ cells at day 3 after ICH. These results indicate that adoptive transfer of Tregs may provide neuroprotection following ICH in mouse models. PMID- 27678141 TI - Outcome of coexistent overactive bladder symptoms in women with urodynamic urinary incontinence following anti-incontinence surgery. AB - INTRODUCTION AND HYPOTHESIS: The objective was to investigate the outcome of stress urinary incontinence (SUI) and overactive bladder (OAB) symptoms in women with urodynamic stress incontinence (USI) after transobturator sling procedures (TOTs). METHODS: We evaluated 109 consecutive patients with USI, who had undergone TOT in a tertiary hospital between 2012 and 2014. All patients received evaluations, including structured urogynecological questionnaires and pelvic organ prolapse quantification examination before, and 3 and 12 months after surgery. One-hour pad test and urodynamic testing were performed before and 3-6 months postoperatively. Patient demographics, lower urinary tract symptoms, and urodynamic results were analyzed between pure USI and USI with OAB symptoms. RESULTS: Persistent SUI occurred in 8 patients at 3 months (7.3 %) and 7 patients at 12 months (6.4 %) postoperatively. The most common OAB symptom was frequency (54.1 %), followed by urgency urinary incontinence (52.3 %), urinary urgency (42.2 %), and nocturia (33 %). Most of these OAB symptoms were resolved at the 3 month and 12-month follow-ups both in patients treated with TOT only and in those treated with TOT combined with other pelvic surgeries. There was no significant difference in the preoperative urodynamic changes between patients with pure USI and USI without OAB groups. However, postoperative urodynamic results showed a significant decrease in the maximal urethral closure pressure in the group of patients with USI and OAB symptoms, but no significant urodynamic changes in the group with pure USI. CONCLUSIONS: Coexistent OAB symptoms are common in women who were diagnosed with USI and most of these symptoms may resolve 3 and 12 months after TOT. PMID- 27678142 TI - Does the vaginal wall become thinner as prolapse grade increases? AB - INTRODUCTION AND HYPOTHESIS: The pathophysiology of prolapse is not well understood. However, two main theories predominate: either the fibromuscular layer of the vagina develops a defect/tears away from its supports, or its tissues are stretched and attenuated. The aim of this study was to assess how vaginal wall thickness (VWT) is related to vaginal prolapse. METHODS: The study group comprised 243 women with symptomatic prolapse recruited from the Outpatient Department of a tertiary referral centre for urogynaecology. A history was taken and women were examined to determine their POP-Q score. Using a previously validated technique, ultrasonography was used to measure the mean VWT at three anatomical sites on the anterior and posterior walls. Scores were then compared using t tests, the Kruskal-Wallis test and the Friedman test. RESULTS: The mean age of the patients was 59.7 years (SD 12.0 years range 38 - 84 years). For each measurement VWT reduced as prolapse grade increased until the prolapse extended beyond the hymen. Women with grade 3 prolapse had a significantly higher mean VWT than women with grade 1 or 2 contained prolapse. Menopause status did not have a significant effect on the VWT. CONCLUSIONS: VWT is lower in women with vaginal prolapse until the prolapse extends beyond the hymen and then VWT is thicker and comparable with women without prolapse. This may be explained by changes in the vaginal tissue including reduction of collagen, elastin and smooth muscle, as well as fibrosis in exposed tissues, rather than by defects in the vagina. PMID- 27678144 TI - Bladder rupture with incomplete rupture of the uterus. PMID- 27678143 TI - Validation of the International Urogynecology Association's Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire in Arabic. AB - INTRODUCTION AND HYPOTHESIS: A valid and reliable Arabic version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-revised (PISQ-IR) is needed. METHODS: Of 238 Saudi Arabian women who fulfilled the inclusion criteria, 227 were recruited. A detailed history was obtained and pelvic examination was performed in all participants. An Arabic version of the PISQ-IR was administered with three quality of life measures. Reliability was assessed by factor analysis, and internal consistency was measured with Cronbach's alpha. Face validity was established with translation, back-translation, and cognitive reviews. Criterion validity was determined by analysing the correlations between the responses and the clinical examinations and by comparing the responses with those to other validated measures of incontinence and prolapse. RESULTS: Overall, 67 % of the women were categorized as sexually active and 33 % as sexually inactive. The overall frequency of urinary incontinence was highest (85.5 %), followed by prolapse (59 %) and fecal incontinence (53.3 %). The average score in the factor analysis for dimensions of sexual inactivity was 2.7 and Cronbach's alpha was 0.61; an item-by-item assessment of the majority of the scales showed an alpha value of >0.75, suggesting a moderate-to-high internal consistency. Regarding external validity, strong negative correlations were found with the Pelvic Organ Prolapse Distress Inventory, the Colorectal-Anal Distress Inventory (CRADI), and the Pelvic Floor Impact Questionnaire (PFIQ) in the sexually active group, and positive correlations were found with the CRADI and PFIQ in the sexually inactive group. CONCLUSIONS: The Arabic version of the PISQ-IR is reliable and valid for assessing sexual function in Arabic-speaking women with pelvic floor disorders. PMID- 27678146 TI - A Comparison of Adsorption, Reduction, and Polymerization of the Plutonyl(VI) and Uranyl(VI) Ions from Solution onto the Muscovite Basal Plane. AB - X-ray scattering techniques [in situ resonant anomalous X-ray reflectivity (RAXR) and specular crystal truncation rods (CTR)] were used to compare muscovite (001) surfaces in contact with solutions containing either 0.1 mM plutonyl(VI) or 1 mM uranyl(VI) at pH = 3.2 +/- 0.2, I(NaCl) = 0.1 M, as well as in situ grazing incidence X-ray absorption near-edge structure (GI XANES) spectroscopy and ex situ alpha spectrometry. Details of the surface coverage are found to be very different. In the case of Pu, alpha spectrometry finds a surface coverage of 8.3 Pu/AUC (AUC = 46.72 A2, the unit cell area), far in excess of the 0.5 Pu/AUC expected for ionic adsorption of PuO22+. GI XANES results show that Pu is predominantly tetravalent on the surface, and the CTR/RAXR results show that the adsorbed Pu is broadly distributed. Taken together with previous findings, the results are consistent with adsorption of Pu in the form of Pu(IV)-oxo nanoparticles. In contrast, uranyl shows only negligible, if any, adsorption according to all methods applied. These results are discussed and compared within the context of known Pu and U redox chemistry. PMID- 27678147 TI - Advances in proteomic study of cardiac amyloidosis: progress and potential. AB - INTRODUCTION: More than ten distinct forms of amyloidoses that can involve the heart have been described, classified according to which protein originates the deposits. Cardiac amyloid infiltration translates into progressive and often life threatening cardiomyopathy, but disease severity, prognosis and treatment drastically differ according to the amyloidosis type. The notion that protein misfolding and aggregation play a more general role in human cardiomyopathies has further raised attention towards the definition of the proteotoxicity mechanisms. Areas covered: Mass spectrometry-based proteomics plays an important role as a diagnostic tool and for understanding the molecular bases of amyloid cardiomyopathies. The landscape of applications of proteomics to the study of cardiac amyloidoses and amyloid-related cardiotoxicity is summarized, with a critical synthesis of the major achievements. Expert commentary: Current strengths and limitations of proteomics in the clinical setting and in translational research on amyloid cardiomyopathy are discussed, with the foreseen potential future directions in the field. PMID- 27678145 TI - De novo stress urinary incontinence after pelvic organ prolapse surgery in women without occult incontinence. AB - INTRODUCTION AND HYPOTHESIS: There is a paucity of data evaluating the risk of de novo stress urinary incontinence (SUI) after surgery for pelvic organ prolapse (POP) in women with no preoperative occult SUI. We hypothesized that apical suspension procedures would have higher rates of de novo SUI. METHODS: This was a retrospective database review of women who had surgery for POP from 2003 to 2013 and developed de novo SUI at >=6 months postoperatively. Preoperatively, all patients had a negative stress test and no evidence of occult SUI on prolapse reduction urodynamics. The primary objective was to establish the incidence of de novo SUI in women with no objective evidence of preoperative occult SUI after POP surgeries at >=6 months. RESULTS: A total number of 274 patients underwent POP surgery. The overall incidence of de novo SUI was 9.9 % [95 % confidence interval (CI) 0.07-0.14]. However, the incidence of de novo SUI in those with no baseline complaint of SUI was 4.4 % (95 % CI 0.03-0.1). There was no difference in de novo SUI rates between apical [9.7 % (n = 57)] and nonapical [10.5 %, (n = 217] procedures (p = 0.8482). Multivariate logistic regression identified sacrocolpopexy [adjusted odds ratio (OR) 4.54, 95 % CI 1.2-14.7] and those with a baseline complaint of SUI (adjusted OR 5.1; 95 % CI 2.2-12) as risk factors for de novo SUI. CONCLUSIONS: The incidence of de novo SUI after surgery for POP without occult SUI was 9.9 %. We recommend counseling patients about the risk of de novo SUI and offering a staged procedure. PMID- 27678148 TI - The effect of childhood trauma and Five-Factor Model personality traits on exposure to adult life events in patients with psychotic disorders. AB - INTRODUCTION: Recent life events are associated with transition to and outcome in psychosis. Childhood trauma and personality characteristics play a role in proneness to adult life events. However, little is known about the relative contribution and interrelatedness of these characteristics in psychotic disorders. Therefore, we investigated whether Five-Factor Model (FFM) personality traits and childhood trauma (abuse and neglect) predict adult life events, and whether the effect of childhood trauma on life events is mediated by personality traits. METHOD: One hundred and sixty-three patients with psychotic disorders were assessed at baseline on history of childhood maltreatment and FFM personality traits, and on recent life events at 3-year follow-up. RESULTS: Childhood abuse is associated with negative life events, and part of the effect of childhood abuse on negative life events is mediated by openness to experience. Openness to experience and extraversion are associated with more positive and negative life events. Childhood neglect and lower extraversion are related to experiencing less positive events. CONCLUSION: The association between childhood trauma and recent life events is partly mediated by personality. Future research could focus on mechanisms leading to positive life events, as positive life events may buffer against development of mental health problems. PMID- 27678150 TI - Age-specific mixing generates transient outbreak risk following critical-level vaccination. AB - Measles elimination goals have been adopted in a range of countries, sub-regions, and regions since the WHO declared an elimination goal by 2015 or 2020. All countries attempt to achieve and maintain high coverage through routine immunization programmes. This routine strategy, however, does not ensure the elimination goal of measles. Many developed countries, such as the United States, that have succeeded in interrupting measles transmission earlier, are now experiencing outbreaks with an increasing number of cases. Using a stochastic, age-structured model of measles vaccination dynamics, we explore and characterize the transient dynamics of measles susceptibility in the years following the implementation of routine vaccination at the herd immunity threshold. We demonstrate how a population could face risks of potentially large outbreaks even within few years of vaccination. We characterize different risk profiles depending on the incidence pattern in the years prior to vaccination. These results suggest that the classic critical vaccination threshold is necessary to achieve herd immunity, but not sufficient to prevent long periods of transient, super-critical dynamics. Our results suggest the need of future work for more careful monitoring of the impacts of current immunization programmes, and developing models that take into account more complicated vaccination strategies, demographic factors, and population movements. PMID- 27678149 TI - Modulation of Behavioral Deficits and Neurodegeneration by Tannic Acid in Experimental Stroke Challenged Wistar Rats. AB - Oxidative stress and inflammatory responses play a critical contributing factor in cerebral ischemia and reperfusion, which lead to lipid peroxidation and neuronal dysfunction that may represent a target for therapeutic intervention. The present study was aimed to elucidate the neuroprotective effect of tannic acid (TA), a natural polyphenol with potential antioxidant and antiinflammatory properties on middle cerebral artery occlusion (MCAO) model in rats. To test this hypothesis, male Wistar rats were pretreated with TA (50 mg/kg b.wt.) and then subjected to 2-h MCAO followed by 22 h of reperfusion. After 2-h MCAO/22-h reperfusion, neurological deficit, infarct sizes, activities of antioxidant enzymes, cytokine level, histology, and immunohistochemistry were used to analyze the expression of glial fibrillary acidic protein (GFAP) in ischemic brain. The pretreatment of TA showed a marked reduction in infarct size, improved neurological function, suppressed neuronal loss, and downregulated the GFAP expression in MCAO rats. A significantly depleted activity of antioxidant enzymes and content of glutathione in MCAO group were protected significantly in MCAO group pretreated with TA. Conversely, the elevated level of thiobarbituric acid reactive species and cytokines in MCAO group was attenuated significantly in TA pretreated group when compared with MCAO group. The results indicated that TA protected the brain from damage caused by MCAO, and this effect may thorough diminish the oxidative stress and inflammatory responses. PMID- 27678151 TI - The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment. AB - OBJECTIVES: To test the effects of bolus supplementation of branched-chain amino acids (BCAA) on skeletal muscle mass, strength, and function in patients with rheumatic disorders taking glucocorticoid (GC). METHODS: Patients with rheumatic disorders treated with prednisolone (>=10 mg/day) were randomized to ingest additional daily 12 g of BCAA (n = 9) or not (n = 9) for 12 weeks. At baseline, and 4, 8, and 12 weeks, they underwent bioelectrical impedance analysis, muscle strength and functional tests, and computed tomography analysis for cross sectional area of mid-thigh muscle. RESULTS: Disease activities of the patients were well controlled and daily GC dose was similarly reduced in both groups. Limb muscle mass was recovered in both groups. Whole-body muscle mass and muscle strength and functional mobility were increased only in BCAA (+) group. The effects of BCAA supplementation on recovering skeletal muscle mass were prominent in particular muscles including biceps femoris muscle. CONCLUSIONS: This trial is the first-in-man clinical trial to demonstrate that BCAA supplementation might be safe and, at least in part, improve skeletal muscle mass, strength, and function in patients with rheumatic disorders treated with GC. PMID- 27678153 TI - Correlations of maternal neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight. AB - OBJECTIVE: The aim of this study is to investigate the possible correlation of hemogram parameters including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight and gestational week. MATERIALS AND METHODS: This prospective study has been conducted with 783 patients. The maternal age, parity, gestational age, type of delivery, values of complete blood count (CBC) variables and the weight of newborn were recorded. We analyzed the statistical differences between the NLR, PLR, hemoglobin (HGB), platelet distribution width (PDW), red cell distribution width (RDW), mean platelet volume (MPV), platelet, neutrophil, lymphocyte and white blood cells (WBC) in terms of the birth weight. RESULTS: There was no statistically significant difference in the NLR in terms of the birth weight (p = 0.097), whereas there was a statistically significant difference in the PLR (p < 0.001). In correlation analyses, a linear, negative, weak and statistically significant correlation was detected between NLR and PLR with the birth weight of infant and gestational week (p = 0.011 and p < 0.001, respectively). CONCLUSION: This prospective study is the first in the literature which investigates the correlation of NLR and PLR with the week of birth and birth weight of the infant. Our study suggested that the maternal NLR and PLR are negatively correlated with the week of birth and birth weight of the infant. PMID- 27678152 TI - In Silico prediction of the molecular basis of ClTx and AaCTx interaction with matrix metalloproteinase-2 (MMP-2) to inhibit glioma cell invasion. AB - Glioblastoma is the deadliest type of brain cancer. Treatment could target the Matrix metalloproteinase-2 (MMP-2), which is known to be involved in the invasion process of glioblastoma cells. But current available inhibitors are not selective to MMP-2 due to their interaction with the catalytic binding site, which is highly conserved in all MMPs structures. Interestingly, members of the chloride channel blocker scorpion toxins, such as chlorotoxin (ClTx) and AaCTx, inhibit glioblastoma cell invasion and show a promising therapeutic potential. Indeed, it has been shown that CITx inhibits selectively MMP-2 and was also able to cross the blood brain and tissue barriers. Although ClTx and AaCTx show high sequence similarity, AaCTx is ten times less active than ClTx. By using molecular modeling, molecular dynamics and MM-PB(GB)SA free energy estimation, we present the first computational study reporting the interaction mode of ClTx/AaCTx with MMP-2. We found that the two peptides probably act on an exosite of MMP-2 comprising mainly residues from the collagen binding domain, a feature that could be exploited to enhance the selectivity toward MMP-2. van der Waals and hydrophobic forces are the primary mediators of this interaction. The N- and C termini of the two peptides harbor the key residues of the interaction spread across a conserved amino acid patch. In particular, F6 contributes mostly to the binding free energy in ClTx. We also suggest that the lack of the C-terminal arginine and the residues P10 and R24, might be responsible for altering the activity of AaCTx toward glioblastoma cells compared to ClTx. PMID- 27678156 TI - UK must stop arms sales to Saudi Arabia in light of bombings of Yemeni health facilities, says charity. PMID- 27678154 TI - A cross-sectional model of eating disorders in Argentinean overweight and obese children. AB - Despite the fact that past research identified childhood obesity as an antecedent of eating disorders, not all obese children further develop this pathology. With this regard, our first purpose was to isolate which characteristics differentiate overweight children who have an eating disorder from those who have not. Second, considering that there is little evidence collected in Latin American countries, we provided overweight children data from an Argentinean sample. Specifically, we investigated if weight-teasing, perfectionism, disturbed eating attitudes and behaviors, and body image dissatisfaction are related to the occurrence of an eating disorder in 100 school-aged overweight/obese children (37 girls and 63 boys; mean age 10.85, SD 0.88). Participants completed self-report instruments and were interviewed between 1 and 2 months later to confirm the presence of eating disorders. Seventeen percent participants confirmed to have an eating disorder. Further, the multivariate logistic analysis revealed that perfectionism (Exp beta = 1.19) and disturbed eating attitudes and behaviors (Exp beta = 4.78) were jointly associated with the presence of an eating disorder. These results were maintained even when the overall model was adjusted for covariates such as age, gender, body mass index, and school type. Weight-teasing and body image dissatisfaction did not contribute to the multivariate model. Prevalence rates of ED and model findings were discussed. PMID- 27678157 TI - Mechanism for neurotropic action of vorinostat, a pan histone deacetylase inhibitor. AB - In this study we investigated the neurotrophic actions of vorinostat (suberoylanilide hydroxamic acid, SAHA), a class I and class II HDAC inhibitor, on the differentiation of Neuroscreen-1 (NS-1) cells. NS-1 cell is a subclone of the rat pheochromocytoma cell line (PC 12). Vorinostat independently induced neurite outgrowth in NS-1 cells. The NS-1 cells were further interrogated for the effects of vorinostat on intracellular neurotrophin signaling pathways, to understand its mechanism of neurotrophic action. Selective inhibitors of MEK1/2 (PD98059 and U0126), phosphoinositide 3-kinase (PI3K) (LY294002) and tyrosine kinase A (TrkA) (GW441756) were employed for these interrogations. Our results suggest that neurite outgrowth mediated by both nerve growth factor (NGF), an intrinsic neurotrophin, and vorinostat were blocked by the inhibitors of MEK1/2 & PI3K. Vorinostat induced phosphorylation of ERK1/2 occurs at 2h post treatment. Phosphorylation of ERK was abolished in presence of U0126, further confirming the role of ERK pathway in vorinostat-induced differentiation of NS-1 cells. Vorinostat-induced neurite outgrowth also involves the activation of upstream extracellular kinase TrkA, as both vorinostat mediated neurite outgrowth and activation of ERK were attenuated in presence of the TrkA inhibitor, GW441756. Vorinostat also stimulated hyperacetylation of alpha-tubulin and histones H3/H4 in NS-1 cells. The results suggest that vorinostat exerts a positive effect on the neuritogenesis via activation of MEK1/2 & PI3K pathways involving an upstream kinase, TrkA. Bioactive small molecules with neurotrophic and neuritogenic actions, like vorinostat identified in the present study, hold great promise as therapeutic agents for treatment of neurodegenerative diseases and neuronal injuries by virtue of their ability to stimulate neuritic outgrowth. PMID- 27678155 TI - The D-form of a novel heparan binding peptide decreases cytomegalovirus infection in vivo and in vitro. AB - Human cytomegalovirus (HCMV) infection in utero can lead to congenital sensory neural hearing loss and mental retardation. Reactivation or primary infection can increase the morbidity and mortality in immune suppressed transplant recipients and AIDS patients. The current standard of care for HCMV disease is nucleoside analogs, which can be nephrotoxic. In addition resistance to current treatments is becoming increasingly common. In an effort to develop novel CMV treatments, we tested the effectiveness of the D-form of a novel heparan sulfate binding peptide, p5RD, at reducing infection of ganciclovir (GCV) resistant HCMVs in vitro and MCMV in vivo. HCMV infection was reduced by greater than 90% when cells were pretreated with p5RD. Because p5RD acts by a mechanism unrelated to those used by current antivirals, it was effective at reducing GCV resistant HCMVs by 85%. We show that p5RD is resistant to common proteases and serum inactivation, which likely contributed to its ability to significantly reduced infection of peritoneal exudate cells and viral loads in the spleen and the lungs in vivo. The ability of p5RD to reduce HCMV infectivity in vitro including GCV resistant HCMVs and MCMV infection in vivo suggests that this peptide could be a novel anti-CMV therapeutic. PMID- 27678159 TI - Regardless of etiology, progressive renal disease causes ultrastructural and functional alterations of peritubular capillaries. AB - Progressive renal diseases are associated with rarefaction of peritubular capillaries, but the ultrastructural and functional alterations of the microvasculature are not well described. To study this, we analyzed different time points during progressive kidney damage and fibrosis in 3 murine models of different disease etiologies. These models were unilateral ureteral obstruction, unilateral ischemia-reperfusion injury, and Col4a3-deficient mice, we analyzed ultrastructural alterations in patient biopsy specimens. Compared with kidneys of healthy mice, we found a significant and progressive reduction of peritubular capillaries in all models analyzed. Ultrastructurally, compared with the kidneys of control mice, focal widening of the subendothelial space and higher numbers of endothelial vacuoles and caveolae were found in fibrotic kidneys. Quantitative analysis showed that peritubular capillary endothelial cells in fibrotic kidneys had significantly and progressively reduced numbers of fenestrations and increased thickness of the cell soma and lamina densa of the capillary basement membrane. Similar ultrastructural changes were also observed in patient's kidney biopsy specimens. Compared with healthy murine kidneys, fibrotic kidneys had significantly increased extravasation of Evans blue dye in all 3 models. The extravasation could be visualized using 2-photon microscopy in real time in living animals and was mainly localized to capillary branching points. Finally, fibrotic kidneys in all models exhibited a significantly greater degree of interstitial deposition of fibrinogen. Thus, peritubular capillaries undergo significant ultrastructural and functional alterations during experimental progressive renal diseases, independent of the underlying injury. Analyses of these alterations could provide read-outs for the evaluation of therapeutic approaches targeting the renal microvasculature. PMID- 27678160 TI - What if there were no new antibiotics? A look at alternatives. AB - INTRODUCTION: Bacterial resistance to antibiotics is increasing worldwide, due to the emergence of multidrug-resistant strains. With this panorama, there is a serious danger that we may be entering the 'post-antibiotic era'. Areas covered: We assess why so few new classes of antibiotics have been developed in the past years and discuss a variety of treatments that may be able to replace antimicrobials: monoclonal antibodies, bacteriophages, stem cells and anti virulence agents such as liposomes. Expert commentary: There are a series of economic, scientific-research and regulatory reasons for the scarcity of new antimicrobials. New approaches are needed to combat infections. Innovative strategies like Eco-Evo drugs and innovative delivery methods such as aerosol or nanoparticle administration require a new management paradigm, in combination with rapid molecular diagnostic tests. Biopharma, clinical researchers, regulatory agencies, governments and investors must work together in the attempts to achieve effective treatment for infections caused by MDR organisms. PMID- 27678158 TI - Human kidney pericytes produce renin. AB - Pericytes, perivascular cells embedded in the microvascular wall, are crucial for vascular homeostasis. These cells also play diverse roles in tissue development and regeneration as multi-lineage progenitors, immunomodulatory cells and as sources of trophic factors. Here, we establish that pericytes are renin producing cells in the human kidney. Renin was localized by immunohistochemistry in CD146 and NG2 expressing pericytes, surrounding juxtaglomerular and afferent arterioles. Similar to pericytes from other organs, CD146+CD34-CD45-CD56- renal fetal pericytes, sorted by flow cytometry, exhibited tri-lineage mesodermal differentiation potential in vitro. Additionally, renin expression was triggered in cultured kidney pericytes by cyclic AMP as confirmed by immuno-electron microscopy, and secretion of enzymatically functional renin, capable of generating angiotensin I. Pericytes derived from second trimester human placenta also expressed renin in an inducible fashion although the renin activity was much lower than in renal pericytes. Thus, our results confirm and extend the recently discovered developmental plasticity of microvascular pericytes, and may open new perspectives to the therapeutic regulation of the renin-angiotensin system. PMID- 27678162 TI - Reconstructing pedigrees using probabilistic analysis of ISSR amplification. AB - Data obtained from ISSR amplification may readily be extracted but only allows us to know, for each gene, if a specific allele is present or not. From this partial information we provide a probabilistic method to reconstruct the pedigree corresponding to some families of diploid cultivars. This method consists in determining for each individual what is the most likely couple of parent pair amongst all older individuals, according to some probability measure. The construction of this measure bears on the fact that the probability to observe the specific alleles in the child, given the status of the parents does not depend on the generation and is the same for each gene. This assumption is then justified from a convergence result of gene frequencies which is proved here. Our reconstruction method is applied to a family of 85 living accessions representing the common broom Cytisus scoparius. PMID- 27678161 TI - Stereoselective alkoxycarbonylation of unactivated C(sp3)-H bonds with alkyl chloroformates via Pd(II)/Pd(IV) catalysis. AB - Several examples on Pd-catalysed carbonylation of methyl C(sp3)-H bonds with gaseous CO via Pd(II)/Pd(0) catalysis have been reported. However, methylene C(sp3)-H carbonylation remains a great challenge, largely due to the lack of reactivity of C-H bonds and the difficulty in CO migratory insertion. Herein, we report the stereoselective alkoxycarbonylation of both methyl and methylene C(sp3)-H bonds with alkyl chloroformates through a Pd(II)/Pd(IV) catalytic cycle. A broad range of aliphatic carboxamides and alkyl chloroformates are compatible with this protocol. In addition, this process is scalable and the directing group could be easily removed under mild conditions with complete retention of configuration. PMID- 27678163 TI - Sensitive inexpensive HPLC determination of four antiepileptic drugs in human plasma: application to PK studies. AB - AIM: Recently, polytherapy regimen has been introduced for the treatment of epileptic patients for better seizure control with lesser side effects and better control of multiple seizure types. METHODOLOGY: A simple, sensitive and highly specific reversed-phase HPLC method was developed for simultaneous determination of four antiepileptic drugs (AEDs), levetiracetam, lamotrigine, oxcarbazepine and carbamazepine, in real human plasma without interference from endogenous components of plasma. CONCLUSION: The method was proved to be linear in the range of 0.5-50 ug/ml for all drugs. It was successfully applied for clinical PK study of the AEDs in healthy volunteers following single administration. Also, this method was applied for simultaneous determination of the studied drugs in volunteers' plasma receiving synergistic binary combinations from the four AEDs when used as add-on therapy. The good precision and selectivity of the developed method allow it to be used for routine therapeutic drug monitoring of such drugs as a useful tool in epilepsy management. PMID- 27678164 TI - Catching prey with the antennae - The larval head of Corethrella appendiculata (Diptera: Corethrellidae). AB - The larval cephalic morphology of Corethrella appendiculata Grabham, 1906 is described and documented in detail. The observed features are compared to conditions found in Chaoboridae, Culicidae, and other culicomorph families. The function of antennae, mouthparts and associated muscles is interpreted based on the morphological results. The prey catching mechanism is compared to what occurs in other predaceous larvae of Culicomorpha. The cephalic larval morphology is discussed with respect to homology and possible phylogenetic implications. The horizontal frontoclypeal antennal grooves and the lateral rows of strongly developed bristles are likely larval autapomorphies of Corethrellidae. The presence of raptorial antennae is a highly unusual apomorphy shared with Chaoboridae. The systematic position of Corethrellidae remains ambiguous. PMID- 27678165 TI - 4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress. AB - Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs) has been identified as a major cause of osteoporosis. However, the molecular mechanisms underlying GC-induced osteoporosis remain elusive. This study was conducted to make clear the mechanism of GC-induced osteoblast apoptosis and to examine whether reduction of ER stress by 4-PBA inhibited osteoblast apoptosis. After treatment with dexamethasone (Dex) or hydrocortisone, cell viability was assessed using an MTT assay. Flow cytometry was performed to assess the apoptosis of MC3T3 E1 cells. The expression levels of ER stress-related proteins (CHOP, GRP78, eIF2alpha, and phospho-eIF2alpha) and apoptosis-related proteins (cleaved Caspase 3, Bcl-2, and Bax) in MC3T3-E1 cells were measured by Western blot analysis. We found that both Dex and hydrocortisone reduced cell proliferation and promoted apoptosis in MC3T3-E1 cells. In addition, the protein expression levels of cleaved Caspase-3 and Bax increased and the protein expression level of Bcl-2 decreased in MC3T3-E1 cells exposed to Dex. In addition, the Dex exposure also resulted in a release of cytochrome c (Cyt C) from mitochondria. The cellular ATP content was decreased following prolonged treatment with Dex. 4-PBA attenuated ER stress and mitochondrial dysfunction induced by Dex in MC3T3-E1 cells. Dex mediated apoptosis of MC3T3-E1 cells is aggravated by ER stress. Moreover, Dex induced apoptosis in MC3T3-E1 cells was inhibited by 4-PBA, suggesting that ER stress involved in Dex-induced apoptosis. In conclusion, inhibition of ER stress by 4-PBA could reduce GC-induced apoptosis in MC3T3-E1 cells. PMID- 27678166 TI - Shape and Displacement Fluctuations in Soft Vesicles Filled by Active Particles. AB - We investigate numerically the dynamics of shape and displacement fluctuations of two-dimensional flexible vesicles filled with active particles. At low concentration most of the active particles accumulate at the boundary of the vesicle where positive particle number fluctuations are amplified by trapping, leading to the formation of pinched spots of high density, curvature and pressure. At high concentration the active particles cover the vesicle boundary almost uniformly, resulting in fairly homogeneous pressure and curvature, and nearly circular vesicle shape. The change between polarized and spherical shapes is driven by the number of active particles. The center-of-mass of the vesicle performs a persistent random walk with a long time diffusivity that is strongly enhanced for elongated active particles due to orientational correlations in their direction of propulsive motion. In our model shape-shifting induces directional sensing and the cell spontaneously migrate along the polarization direction. PMID- 27678167 TI - Comparative transcriptome assembly and genome-guided profiling for Brettanomyces bruxellensis LAMAP2480 during p-coumaric acid stress. AB - Brettanomyces bruxellensis has been described as the main contaminant yeast in wine production, due to its ability to convert the hydroxycinnamic acids naturally present in the grape phenolic derivatives, into volatile phenols. Currently, there are no studies in B. bruxellensis which explains the resistance mechanisms to hydroxycinnamic acids, and in particular to p-coumaric acid which is directly involved in alterations to wine. In this work, we performed a transcriptome analysis of B. bruxellensis LAMAP248rown in the presence and absence of p-coumaric acid during lag phase. Because of reported genetic variability among B. bruxellensis strains, to complement de novo assembly of the transcripts, we used the high-quality genome of B. bruxellensis AWRI1499, as well as the draft genomes of strains CBS2499 and0 g LAMAP2480. The results from the transcriptome analysis allowed us to propose a model in which the entrance of p coumaric acid to the cell generates a generalized stress condition, in which the expression of proton pump and efflux of toxic compounds are induced. In addition, these mechanisms could be involved in the outflux of nitrogen compounds, such as amino acids, decreasing the overall concentration and triggering the expression of nitrogen metabolism genes. PMID- 27678168 TI - A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection. AB - Whereas studies have extensively examined the ability of bacteria to influence Plasmodium infection in the mosquito, the tripartite interactions between non entomopathogenic fungi, mosquitoes, and Plasmodium parasites remain largely uncharacterized. Here we report the isolation of a common mosquito-associated ascomycete fungus, Penicillium chrysogenum, from the midgut of field-caught Anopheles mosquitoes. Although the presence of Pe. chrysogenum in the Anopheles gambiae midgut does not affect mosquito survival, it renders the mosquito significantly more susceptible to Plasmodium infection through a secreted heat stable factor. We further provide evidence that the mechanism of the fungus mediated modulation of mosquito susceptibility to Plasmodium involves an upregulation of the insect's ornithine decarboxylase gene, which sequesters arginine for polyamine biosynthesis. Arginine plays an important role in the mosquito's anti-Plasmodium defense as a substrate of nitric oxide production, and its availability therefore has a direct impact on the mosquito's susceptibility to the parasite. While this type of immunomodulatory mechanism has already been demonstrated in other host-pathogen interaction systems, this is the first report of a mosquito-associated fungus that can suppress the mosquito's innate immune system in a way that would favor Plasmodium infection and possibly malaria transmission. PMID- 27678169 TI - Post-9/11 Veterans and Their Partners Improve Mental Health Outcomes with a Self directed Mobile and Web-based Wellness Training Program: A Randomized Controlled Trial. AB - BACKGROUND: Veterans with history of deployment in the Global War on Terror face significant and ongoing challenges with high prevalences of adverse psychological, physical, spiritual, and family impacts. Together, these challenges contribute to an emerging public health crisis likely to extend well into the future. Innovative approaches are needed that reach veterans and their family members with strategies they can employ over time in their daily lives to promote improved adjustment and well-being. OBJECTIVE: The objective of this study was to evaluate effects of use of a Web-based, self-directed program of instruction in mind- and body-based wellness skills to be employed by Global War on Terror veterans and their significant relationship partners on mental health and wellness outcomes associated with postdeployment readjustment. METHODS: We recruited 160 veteran-partner dyads in 4 regions of the United States (San Diego, CA; Dallas, TX; Fayetteville, NC; and New York, NY) through publicity by the Iraq and Afghanistan Veterans of America to its membership. Dyads were randomly allocated to 1 of 4 study arms: Mission Reconnect (MR) program alone, MR plus the Prevention and Relationship Enhancement Program (PREP) for Strong Bonds weekend program for military couples, PREP alone, and waitlist control. We administered a battery of standardized and investigator-generated instruments assessing mental health outcomes at baseline, 8 weeks, and 16 weeks. Dyads in the MR arms were provided Web-based and mobile app video and audio instruction in a set of mindfulness-related stress reduction and contemplative practices, as well as partner massage for reciprocal use. All participants provided weekly reports on frequency and duration of self-care practices for the first 8 weeks, and at 16 weeks. RESULTS: During the first 8-week reporting period, veterans and partners assigned to MR arms used some aspect of the program a mean of 20 times per week, totaling nearly 2.5 hours per week, with only modest declines in use at 16 weeks. Significant improvements were seen at 8 and 16 weeks in measures of posttraumatic stress disorder, depression, sleep quality, perceived stress, resilience, self compassion, and pain for participants assigned to MR arms. In addition, significant reductions in self-reported levels of pain, tension, irritability, anxiety, and depression were associated with use of partner massage. CONCLUSIONS: Both veterans and partners were able to learn and make sustained use of a range of wellness practices taught in the MR program. Home-based, self-directed interventions may be of particular service to veterans who are distant from, averse to, or prohibited by schedule from using professional services. Leveraging the partner relationship may enhance sustained use of self-directed interventions for this population. Use of the MR program appears to be an accessible, low-cost approach that supports well-being and reduces multiple symptoms among post-9/11 veterans and their partners. TRIAL REGISTRATION: Clinicaltrials.gov NCT01680419; https://clinicaltrials.gov/ct2/show/NCT01680419 (Archived by WebCite at http://www.webcitation.org/6jJuadfzj). PMID- 27678170 TI - Characterization of the Pathogenesis of H10N3, H10N7, and H10N8 Subtype Avian Influenza Viruses Circulating in Ducks. AB - Three H10 subtype avian influenza viruses were isolated from domestic ducks in China, designated as SH602/H10N8, FJ1761/H10N3 and SX3180/H10N7, with an intravenous pathogenicity index (IVPI) of 0.39, 1.60, and 1.27, respectively. These H10 viruses showed a complex pathology pattern in different species, although full genome characterizations of the viruses could not identify any molecular determinant underlying the observed phenotypes. Our findings describe the pathobiology of the three H10 subtype AIVs in chickens, ducks, and mice. FJ1761/H10N3 evolved E627K and Q591K substitutions in the gene encoding the PB2 protein in infected mice with severe lung damage, suggesting that H10 subtype avian influenza viruses are a potential threat to mammals. PMID- 27678171 TI - Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes. AB - : Carcinoma-associated fibroblasts (CAF) represent a significant component of pancreatic cancer stroma and are biologically implicated in tumor progression. However, evidence of both cancer-promoting and -restraining properties amongst CAFs suggests the possibility of multiple phenotypic subtypes. Here, it is demonstrated that senescent CAFs promote pancreatic cancer invasion and metastasis compared with nonsenescent control CAFs using in vitro Transwell invasion models and in vivo xenograft mouse models. Screening by gene expression microarray and cytokine ELISA assays revealed IL8 to be upregulated in senescent CAFs. Experimental modulation through IL8 overexpression or receptor inhibition implicates the IL8 pathway as a mediator of the proinvasive effects of senescent CAFs. In a cohort of human pancreatic cancer cases, more abundant stromal senescence as indicated by p16 immunohistochemistry correlated with decreased survival in patients with early-stage disease. These data support senescent fibroblasts as a pathologically and clinically relevant feature of pancreatic cancer. The inhibition of senescent stroma-cancer signaling pathways has the potential to restrain pancreatic cancer progression. IMPLICATIONS: Findings show that senescent cancer-associated fibroblasts secret excess IL8 to promote pancreatic cancer invasion and metastasis; thus, senescent CAFs represent a phenotypic subtype, challenging conventional assumptions that CAFs are a homogeneous population. Mol Cancer Res; 15(1); 3-14. (c)2016 AACR. PMID- 27678172 TI - 13C and 15N natural isotope abundance reflects breast cancer cell metabolism. AB - Breast cancer is the most common cancer in women worldwide. Despite the information provided by anatomopathological assessment and molecular markers (such as receptor expression ER, PR, HER2), breast cancer therapies and prognostics depend on the metabolic properties of tumor cells. However, metabolomics have not provided a robust and congruent biomarker yet, likely because individual metabolite contents are insufficient to encapsulate all of the alterations in metabolic fluxes. Here, we took advantage of natural 13C and 15N isotope abundance to show there are isotopic differences between healthy and cancer biopsy tissues or between healthy and malignant cultured cell lines. Isotope mass balance further suggests that these differences are mostly related to lipid metabolism, anaplerosis and urea cycle, three pathways known to be impacted in malignant cells. Our results demonstrate that the isotope signature is a good descriptor of metabolism since it integrates modifications in C partitioning and N excretion altogether. Our present study is thus a starting point to possible clinical applications such as patient screening and biopsy characterization in every cancer that is associated with metabolic changes. PMID- 27678174 TI - From the Blood to the Central Nervous System: A Nanoparticle's Journey Through the Blood-Brain Barrier by Transcytosis. AB - Designing nanoparticles that effectively enter the central nervous system (CNS) rapidly and without alteration is one of the major challenges in the use of nanotechnology for the brain. In this chapter, we explore the process of transcytosis, a receptor-mediated transport pathway that permits endogenous macromolecules to enter the CNS by crossing the blood-brain barrier. Transcytosis across the blood-brain barrier involves a number of distinct stages, including receptor binding, endocytosis into a transport vesicle, trafficking of the vesicle to the opposite side of the cell, and finally exocytosis and release of cargo. For each stage, we discuss the current knowledge on biological, physiological, and physical factors that influence nanoparticle transit through that stage of transcytosis, with implications for nanoparticle design. Finally, we look at the current progress in designing nanoparticles that exploit transcytosis for CNS delivery. PMID- 27678173 TI - Recent Trends in Nanotechnology Toward CNS Diseases: Lipid-Based Nanoparticles and Exosomes for Targeted Therapeutic Delivery. AB - Central nervous system (CNS) diseases constitute a set of challenging pathological conditions concerning diagnosis and therapeutics. For most of these disorders, there is a lack of early diagnosis, biomarkers to allow proper follow up of disease progression and effective therapeutic strategies to allow a persistent cure. The poor prognosis of most CNS diseases is, therefore, a global concern, especially regarding chronic age-related neurodegenerative disorders, which are already considered problems of public health due to the increasing average of life expectancy. The difficulties associated with the treatment of CNS diseases are owed, at least in part, to very specific characteristics of the brain and spinal cord, when compared to peripheral organs. In this regard, the CNS is physically and chemically protected by the blood-brain barrier (BBB), which, while maintaining essential brain homeostasis, significantly restricts the delivery of most therapeutic agents to the brain parenchyma. On the other hand, regenerative properties of the tissue are lacking, meaning that a CNS insult resulting in neuronal death is a permanent phenomenon. Approaches for transposing the BBB aiming to treat CNS diseases, relying on specific properties of nanosystems, have been reported for therapeutic delivery to CNS without interfering with the normal function of the brain. In this chapter, we address the latest advances concerning the principles of such approaches, employing lipid based nanoparticles and cell-produced exosomes as drug and nucleic acid delivery systems, and summarize recent example of applications in the context of neurological diseases. Major achievements obtained in preclinical studies and the trends identified by these studies are emphasized to provide new prospects for further developments in this area, thus enabling us to move from the research realm to the clinical arena. PMID- 27678175 TI - Application of Nanomedicine to the CNS Diseases. AB - Drug delivery to the brain is a challenge because of the many mechanisms that protect the brain from the entry of foreign substances. Numerous molecules which could be active against brain disorders are not clinically useful due to the presence of the blood-brain barrier. Nanoparticles can be used to deliver these drugs to the brain. Encapsulation within colloidal systems can allow the passage of nontransportable drugs across this barrier by masking their physicochemical properties. It should be noted that the status of the blood-brain barrier is different depending on the brain disease. In fact, in some pathological situations such as tumors or inflammatory disorders, its permeability is increased allowing very easy translocation of carriers. This chapter gathers the promising results obtained by using nanoparticles as drug delivery systems with the aim to improve the therapy of some CNS diseases such as brain tumor, Alzheimer's disease, and stroke. The data show that several approaches can be investigated: (1) carrying drug through a permeabilized barrier, (2) crossing the barrier thanks to receptor-mediated transcytosis pathway in order to deliver drug into the brain parenchyma, and also (3) targeting and treating the endothelial cells themselves to preserve locally the brain tissue. The examples given in this chapter contribute to demonstrate that delivering drugs into the brain is one of the most promising applications of nanotechnology in clinical neuroscience. PMID- 27678176 TI - Carbohydrate Nanoparticles for Brain Delivery. AB - Many brain tumors and neurological diseases can greatly benefit from the use of emerging nanotechnologies based on targeted nanomedicines that are able to noninvasively transport highly potent and specific pharmaceuticals across the blood-brain barrier. Carbohydrates have received considerable interest as materials for drug carriers due to their natural origin and inherent biodegradability and biocompatibility, as well as due to their hydrophilic character and ease of chemical modification combined with low cost and the possibility for large-scale manufacturing. This chapter provides an overview of the latest research involving the use of carbohydrate-based nanoparticles for drug delivery to the central nervous system. After reviewing the challenges posed by delivering drugs into the brain, the current state-of-the-art approaches for delivery of actives across the blood-brain barrier, including invasive and noninvasive strategies, are presented. A particular focus has been placed on chitosan polymers as they are among the most promising carbohydrate nanocarriers for the preparation and testing of chitosan-based nanomedicines that led, in preclinical proof-of-concept studies, to enhanced brain drug levels and increased pharmacodynamics responses after intravenous, nasal, and oral administration. While chitosan nanoparticles are to date among the most studied and most promising carriers, approaches based on other polysaccharides such as dextran, pullulan, and cellulose warrant further research in the attempt to advance the existing technologies for overcoming the blood-brain barrier. PMID- 27678178 TI - Metal Nanoparticles as Targeted Carriers Circumventing the Blood-Brain Barrier. AB - Metal nanoparticles have been proposed as a carrier and a therapeutic agent in biomedical field because of their unique physiochemical properties. Due to these physicochemical properties, they can be used in different fields of biomedicine. In relation to this, plasmonic nanoparticles can be used for detection and photothermal destruction of tumor cells or toxic protein aggregates, and magnetic iron nanoparticles can be used for imaging and for hyperthermia of tumor cells. In addition, both therapy and imaging can be combined in one nanoparticle system, in a process called theranostics. Metal nanoparticles can be synthesized to modulate their size and shape, and conjugated with different ligands, which allow their application in drug delivery, diagnostics, and treatment of central nervous system diseases. This review is focused on the potential applications of metal nanoparticles and their capability to circumvent the blood-brain barrier (BBB). Although many articles have demonstrated delivery of metal nanoparticles to the brain by crossing the BBB after systemic administration, the percentage of the injected dose that reaches this organ is low in comparison to others, especially the liver and spleen. In connection with this drawback, we elaborate the architecture of the BBB and review possible mechanisms to cross this barrier by engineered nanoparticles. The potential uses of metal nanoparticles for treatment of disorders as well as related neurotoxicological considerations are also discussed. Finally, we bring up for discussion a direct and relatively simpler solution to the problem. We discuss this in detail after having proposed the use of the intranasal administration route as a way to circumvent the BBB. This route has not been extensively studied yet for metal nanoparticles, although it could be used as a research tool for mechanistic understanding and toxicity as well as an added value for medical practice. PMID- 27678177 TI - Gold Nanoparticles for Imaging and Drug Transport to the CNS. AB - Gold nanoparticles with a core size of 2nm covalently coated with glycans to maintain solubility, targeting molecules for brain endothelium, and cargo molecules hold great potential for delivery of therapies into the CNS. They have low toxicity, pass through brain endothelium in vitro and in vivo, and move rapidly through the brain parenchyma. Within minutes of infusion the nanoparticles can be detected in neurons and glia. These nanoparticles are relatively easy to synthesize in association with their surface ligands. They can be detected by electron microscopy, ICP-mass spectrometry, and spectroscopy. However, modification of the basic gold nanoparticle is required for in vivo imaging by MR or radioactive methods. Depending on their surface coat, the nanoparticles cross the brain endothelium by the plasma membrane/cytosolic route (passive transport) or by vesicular transcytosis (active transport). A primary aim of current research is to improve the biodistribution of the nanoparticles for CNS drug delivery. Smaller gold nanoparticles are removed rapidly via the kidney, while larger nanoparticles are taken up by mononuclear phagocytes in various tissues. Receptors selectively located on brain endothelium can act as targets for the nanoparticles, to increase their delivery to the brain. PMID- 27678179 TI - Current Perspective of Carbon Nanotubes Application in Neurology. AB - The recent advances in nanotechnology have allowed new fields of research to investigate cutting edge brain-specific therapies and to tackle the complex brain related disorders. The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain resulting in only few drugs reaching the market to tackle brain disorders. Nanoparticles (NPs) provide a flexible platform for conjugating drugs and targeting ligands and have been extensively researched to facilitate BBB crossing and effective delivery to the brain. In addition, the inherent properties of NPs are being utilized to facilitate other therapeutic possibilities. One example is carbon nanotubes (CNTs), which exhibit several attractive characteristics allowing their use in the brain environment. The properties include a high aspect ratio, the ability to penetrate biological membranes due to their tubular shape and their infrared absorption properties. In this chapter, we review major advances in using CNTs for treating brain tumor and degenerative diseases with special focus on their abilities to cross the BBB following systemic administration, which is the major obstacle for most other NPs. PMID- 27678180 TI - Preface. PMID- 27678182 TI - An update on interventional cardiology: management of CTO, performance of absorbable scaffolds, coronary vasomotion after DES, and antithrombotics. PMID- 27678183 TI - Rene Geronimo Favaloro-a man who dedicated his life and his death to his work. PMID- 27678181 TI - Bioluminescence Microscopy as a Method to Measure Single Cell Androgen Receptor Activity Heterogeneous Responses to Antiandrogens. AB - Cancer cell heterogeneity is well-documented. Therefore, techniques to monitor single cell heterogeneous responses to treatment are needed. We developed a highly translational and quantitative bioluminescence microscopy method to measure single cell androgen receptor (AR) activity modulation by antiandrogens from fluid biopsies. We showed that this assay can detect heterogeneous cellular response to drug treatment and that the sum of single cell AR activity can mirror the response in the whole cell population. This method may thus be used to monitor heterogeneous dynamic treatment responses in cancer cells. PMID- 27678184 TI - The Argentine Federation of Cardiology (FAC). PMID- 27678185 TI - The Argentine Society of Cardiology. PMID- 27678187 TI - Low physical activity responsible for 17% of cardiovascular deaths in Argentina. PMID- 27678188 TI - EACPR country of the month initiative: Hungary. PMID- 27678189 TI - Discovery of the pulmonary circulation, ancient Persia and Michel Servetus (1511 1453). PMID- 27678190 TI - Proteins involved in sleep homeostasis: Biophysical characterization of INC and its partners. AB - The insomniac protein of Drosophila melanogaster (INC) has a crucial role in sleep homeostasis as flies lacking the inc gene exhibit strikingly reduced and poorly consolidated sleep. Nevertheless, in vitro characterizations of INC biophysical properties and partnerships have not been yet reported. Here we report the heterologous expression of the protein and its characterization using a number of different techniques. Present data indicate that INC is endowed with a remarkable stability, which results from the cooperation of the two protein domains. Moreover, we also demonstrated and quantified the ability of INC to recognize its potential partners Cul3 and dGRASP. Taking into account the molecular organization of the protein, these two partners may be anchored simultaneously. Although there is no evident relationship between the reported INC functions and dGRASP binding, our data suggest that INC may cooperate as ligase adaptor to dGRASP ubiquitination. SAXS data collected on the complex between INC and Cul3, which represent the first structural characterization of this type of assemblies, clearly highlight the highly dynamic nature of these complexes. This strongly suggests that the functional behavior of these proteins cannot be understood if dynamic effects are not considered. Finally, the strict analogy of the biochemical/biophysical properties of INC and of its human homolog KCTD5 may reliably indicate that this latter protein and/or the closely related proteins KCTD2/KCTD17 may play important roles in human sleep regulation. PMID- 27678191 TI - miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages. AB - Previous studies have shown that miR-467b plays a central role in the progression of atherosclerosis via regulating LPL expression. However, the regulatory mechanism of miR-467b in regulateing the CE and FC formation is still unclear. Interestingly, computational analysis demonstrated that ACAT1 which converts intracellular FC into the storage form of CE, and ABCA1 which promotes cellular FC efflux may be target gene of miR-467b. Here, we examined whether miR-467b could target ACAT1 and ABCA1, thereby affecting the CE and FC formation in oxLDL treatment RAW 264.7 cells. We found that miR-467b regulates the CE:FC ratio in oxLDL-treatment RAW 264.7 macrophages, and the luciferase activity of ACAT1 is regulated by the miR-467b, but the luciferase activity of ABCA1 has no effect. Furthermore, our data suggested that miR-467b highly regulates the endogenous levels of ACAT1 expression, thereby affecting the CE formation in oxLDL-treatment RAW 264.7 macrophages. Taken together, our findings demonstrate that ACAT1 is a target gene of miR-467b, and miR-467b regulated the CE and FC formation via directly target the ACAT1 3'UTR. PMID- 27678192 TI - Patterns and determinants of dropout from maternity care continuum in Nigeria. AB - BACKGROUND: The maternal, newborn and child health care continuum require that mother/child pair should receive the full package of antenatal, intrapartum and postnatal care in order to derive maximum benefits. Continuity of care is a challenge in sub-Saharan Africa. In this study, we investigate the patterns and factors associated with dropout in the continuum of maternity (antenatal, delivery and postnatal) care in Nigeria. METHOD: Using women recode file from the 2013 Nigeria Demographic and Health Survey, we analysed data on 20,467 women with an index birth within 5 years prior to data collection. Background characteristics and pattern of dropouts were summarised using descriptive statistics. The outcome variable was dropout which we explored in three stages: antenatal, antenatal-delivery, delivery-6 weeks postnatal visit. Multilevel logistic regression models were fitted to identify independent predictors of dropout at each stage. Measure of effect was expressed as Odds Ratio (OR) with 95 % confidence interval (CI). RESULTS: Overall, 12,392 (60.6 %) of all women received antenatal care among whom 38.1 % dropout and never got skilled delivery assistance. Of those who received skilled delivery care, 50.8 % did not attend postnatal visit. The predictors of dropout between antenatal care and delivery include problem with getting money for treatment (OR = 1.18, CI: 1.04-1.34), distance to health facility (OR = 1.31, CI: 1.13-1.52), lack of formal education, being in poor wealth quintile (OR = 2.22, CI: 1.85-2.67), residing in rural areas (OR = 1.98, CI: 1.63-2.41). Regional differences between North East, North West and South West were significant. Between delivery and postnatal visit, the same factors were also associated with dropout. CONCLUSION: The rate of dropout from maternity care continuum is high in Nigeria and driven by low or lack of formal education, poverty and healthcare access problems (distance to facility and difficulty with getting money for treatment). Unexpectedly, dropouts are high in South east and South south as well as in the Northern regions. Intervention programs focusing on community outreach about the benefits of continuum of maternal healthcare package should be introduced especially for women in rural areas and lower socio-economic strata. PMID- 27678193 TI - Depletion of primary cilia from mature dentate granule cells impairs hippocampus dependent contextual memory. AB - The primary cilium, a sensory organelle, regulates cell proliferation and neuronal development of dentate granule cells in the hippocampus. However, its role in the function of mature dentate granule cells remains unknown. Here we specifically depleted and disrupted ciliary proteins IFT20 and Kif3A (respectively) in mature dentate granule cells and investigated hippocampus dependent contextual memory and long-term plasticity at mossy fiber synapses. We found that depletion of IFT20 in these cells significantly impaired context dependent fear-related memory. Furthermore, we tested synaptic plasticity of mossy fiber synapses in area CA3 and found increased long-term potentiation upon depletion of IFT20 or disruption of Kif3A. Our findings suggest a role of primary cilia in the memory function of mature dentate granule cells, which may result from abnormal mossy fiber synaptic plasticity. A direct link between the primary cilia of mature dentate granule cells and behavior will require further investigation using independent approaches to manipulate primary cilia. PMID- 27678194 TI - Surface acting and exhaustion: The moderating role of eudaimonia. AB - Surface acting (faking emotions) is one of the stressors experienced by contact employees during service interactions with customers, and it has implications for workers' exhaustion. One challenge of research and practice is to identify moderators that help to better understand the positive relationships between surface acting and exhaustion. The present study proposes the two dimensions of eudaimonia beliefs about well-being (self-development and contribution-to-others beliefs) as moderators between surface acting and exhaustion. We performed regression analyses with 817 contact employees working in 118 health-care organizations providing services to people with intellectual disability. Results confirmed the hypotheses, showing that contribution-to-others strengthens the link from surface acting to exhaustion, whereas self-development weakens this relationship. Therefore, self-development beliefs act as a protector for workers when they have to deal with situations that require surface acting. PMID- 27678197 TI - High-performance, bare silver nanowire network transparent heaters. AB - Silver nanowire (Ag NW) networks are one of the most promising candidates for the replacement of indium tin oxide (ITO) thin films in many different applications. Recently, Ag-NW-based transparent heaters (THs) showed excellent heating performance. In order to overcome the instability issues of Ag NW networks, researchers have offered different hybrid structures. However, these approaches not only require extra processing, but also decrease the optical performance of Ag NW networks. So, it is important to investigate and determine the thermal performance limits of bare-Ag-NW-network-based THs. Herein, we report on the effect of NW density, contact geometry, applied bias, flexing and incremental bias application on the TH performance of Ag NW networks. Ag-NW-network-based THs with a sheet resistance and percentage transmittance of 4.3 Omega sq(-1) and 83.3%, respectively, and a NW density of 1.6 NW MUm(-2) reached a maximum temperature of 275 degrees C under incremental bias application (5 V maximum). With this performance, our results provide a different perspective on bare-Ag-NW network-based transparent heaters. PMID- 27678195 TI - A unique RPW8-encoding class of genes that originated in early land plants and evolved through domain fission, fusion, and duplication. AB - Duplication, lateral gene transfer, domain fusion/fission and de novo domain creation play a key role in formation of initial common ancestral protein. Abundant protein diversities are produced by domain rearrangements, including fusions, fissions, duplications, and terminal domain losses. In this report, we explored the origin of the RPW8 domain and examined the domain rearrangements that have driven the evolution of RPW8-encoding genes in land plants. The RPW8 domain first emerged in the early land plant, Physcomitrella patens, and it likely originated de novo from a non-coding sequence or domain divergence after duplication. It was then incorporated into the NBS-LRR protein to create a main sub-class of RPW8-encoding genes, the RPW8-NBS-encoding genes. They evolved by a series of genetic events of domain fissions, fusions, and duplications. Many species-specific duplication events and tandemly duplicated clusters clearly demonstrated that species-specific and tandem duplications played important roles in expansion of RPW8-encoding genes, especially in gymnosperms and species of the Rosaceae. RPW8 domains with greater Ka/Ks values than those of the NBS domains indicated that they evolved faster than the NBS domains in RPW8-NBSs. PMID- 27678196 TI - Differences in Hospital Readmission Risk across All Payer Groups in South Carolina. AB - OBJECTIVE: To evaluate differences in hospital readmission risk across all payers in South Carolina (SC). DATA SOURCES/STUDY SETTING: South Carolina Revenue and Fiscal Affairs Office (SCRFA) statewide all payer claims database including 2,476,431 hospitalizations in SC acute care hospitals between 2008 and 2014. STUDY DESIGN: We compared the odds of unplanned all-cause 30-day readmission for private insurance, Medicare, Medicaid, uninsured, and other payers and examined interaction effects between payer and index admission characteristics using generalized estimating equations. DATA COLLECTION: SCRFA receives claims and administrative health care data from all SC health care facilities in accordance with SC state law. PRINCIPAL FINDINGS: Odds of readmission were lower for females compared to males in private, Medicare, and Medicaid payers. African Americans had higher odds of readmission compared to whites across private insurance, Medicare, and Medicaid, but they had lower odds among the uninsured. Longer length of stay had the strongest association with readmission for private and other payers, whereas an increased number of comorbidities related to the highest readmission odds within Medicaid. CONCLUSIONS: Associations between index admission characteristics and readmission likelihood varied significantly with payer. Findings should guide the development of payer-specific quality improvement programs. PMID- 27678199 TI - Interaction of an Iridium(III) Complex with G-Quadruplex DNA and Its Application in Luminescent Switch-On Detection of Siglec-5. AB - Sialic acid (Sia) binding immunoglobulin (Ig)-like lectin-5 (Siglec-5) is a type I transmembrane protein, and it has been demonstrated as a biomarker of granulocytic maturation and acute myeloid leukemia phenotype. Herein we aimed to construct a method that could sensitively detect Siglec-5 by taking advantage of the high affinity and selectivity of the K19 aptamer for its cognate target, and the selective interaction of luminescent iridium(III) transition metal complexes with G-quadruplex DNA. The iridium(III) complex 1 [Ir(tpyd)2(2,9-dmphen)]PF6 (where tpyd =2-(m-tolyl)pyridine; 2,9-dmphen =2,9-dimethyl-1,10-phenanthroline) was synthesized, and it displayed high luminescence for G-quadruplex DNA compared to dsDNA and ssDNA. Additionally, complex 1 exhibited a blue shift luminescence response to c-kit2 G-quadruplex, and the interaction between 1 and G-quadruplexes was discussed based on the results of G-tetrad assay, loop effect assay, and other assays. Then complex 1 was utilized to develop a G-quadruplex-based sensing platform for Siglec-5 in aqueous solution. Upon the addition of Siglec-5, the specific binding of the K19 aptamer sequence results in a conformational change that generates a split G-quadruplex structure, which is then recognized by the G quadruplex-specific iridium(III) complex with an enhanced luminescent response. Futhermore, the use of the assay for detecting Siglec-5 in cellular debris was demonstrated. PMID- 27678198 TI - Web-based bioinformatics workflows for end-to-end RNA-seq data computation and analysis in agricultural animal species. AB - BACKGROUND: Remarkable advances in Next Generation Sequencing (NGS) technologies, bioinformatics algorithms and computational technologies have significantly accelerated genomic research. However, complicated NGS data analysis still remains as a major bottleneck. RNA-seq, as one of the major area in the NGS field, also confronts great challenges in data analysis. RESULTS: To address the challenges in RNA-seq data analysis, we developed a web portal that offers three integrated workflows that can perform end-to-end compute and analysis, including sequence quality control, read-mapping, transcriptome assembly, reconstruction and quantification, and differential analysis. The first workflow utilizes Tuxedo (Tophat, Cufflink, Cuffmerge and Cuffdiff suite of tools). The second workflow deploys Trinity for de novo assembly and uses RSEM for transcript quantification and EdgeR for differential analysis. The third combines STAR, RSEM, and EdgeR for data analysis. All these workflows support multiple samples and multiple groups of samples and perform differential analysis between groups in a single workflow job submission. The calculated results are available for download and post analysis. The supported animal species include chicken, cow, duck, goat, pig, horse, rabbit, sheep, turkey, as well as several other model organisms including yeast, C. elegans, Drosophila, and human, with genomic sequences and annotations obtained from ENSEMBL. The RNA-seq portal is freely available from http://weizhongli-lab.org/RNA-seq . CONCLUSIONS: The web portal offers not only bioinformatics software, workflows, computation and reference data, but also an integrated environment for complex RNA-seq data analysis for agricultural animal species. In this project, our aim is not to develop new RNA-seq tools, but to build web workflows for using popular existing RNA-seq methods and make these tools more accessible to the communities. PMID- 27678202 TI - Introduction to Making Dialysis Adequate-Addressing its Limitations. PMID- 27678200 TI - Transition metal ion FRET uncovers K+ regulation of a neurotransmitter/sodium symporter. AB - Neurotransmitter/sodium symporters (NSSs) are responsible for Na+-dependent reuptake of neurotransmitters and represent key targets for antidepressants and psychostimulants. LeuT, a prokaryotic NSS protein, constitutes a primary structural model for these transporters. Here we show that K+ inhibits Na+ dependent binding of substrate to LeuT, promotes an outward-closed/inward-facing conformation of the transporter and increases uptake. To assess K+-induced conformational dynamics we measured fluorescence resonance energy transfer (FRET) between fluorescein site-specifically attached to inserted cysteines and Ni2+ bound to engineered di-histidine motifs (transition metal ion FRET). The measurements supported K+-induced closure of the transporter to the outside, which was counteracted by Na+ and substrate. Promoting an outward-open conformation of LeuT by mutation abolished the K+-effect. The K+-effect depended on an intact Na1 site and mutating the Na2 site potentiated K+ binding by facilitating transition to the inward-facing state. The data reveal an unrecognized ability of K+ to regulate the LeuT transport cycle. PMID- 27678201 TI - Aqueous humour concentrations of TGF-beta, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy. AB - PURPOSE: To correlate angiogenic cytokines in the aqueous humour with total retinal blood flow in subjects with type 2 diabetes with non-proliferative diabetic retinopathy (NPDR). METHODS: A total of 17 controls and 16 NPDR patients were recruited into the study. Aqueous humour was collected at the start of cataract surgery to assess the concentration of 14 angiogenic cytokines. Aqueous humour was analysed using the suspension array method. Six images were acquired to assess total retinal blood flow (TRBF) using the prototype RTVueTM Doppler Fourier domain optical coherence tomography (Doppler FD-OCT) (Optovue, Inc., Fremont, CA) using a double circular scan protocol, 1 month postsurgery. At the same visit, forearm blood was collected to determine glycosylated haemoglobin (A1c). RESULTS: Transforming growth factor beta (TGF-beta1, TGF-beta2) and PLGF were increased while FGF-1 was reduced in NPDR compared to controls (Bonferroni corrected, p < 0.003 for all). Total retinal blood flow (TRBF) was significantly reduced in the NPDR group compared to controls (33.1 +/- 9.9 versus 43.3 +/- 5.3 MUl/min, p = 0.002). Aqueous FGF-1 significantly correlated with TRBF in the NPDR group (r = 0.71, p = 0.01; r2 = 0.51). In a multiple regression analysis, A1c was found to be a significant predictor of aqueous TGF-beta1 and FGF-1 (p = 0.018 and p = 0.020, respectively). CONCLUSION: Aqueous angiogenic cytokines (TGF beta1, TGF-beta2 and PLGF) were elevated in conjunction with a reduction in TRBF in patients with NPDR compared to controls. Non-invasive measurement of TRBF may be useful for predicting aqueous FGF-1 levels and severity of vasculopathy in DR. PMID- 27678203 TI - Cost and Complications of Local Therapies for Early-Stage Breast Cancer. AB - Background: Guideline-concordant local therapy options for early breast cancer include lumpectomy plus whole breast irradiation (Lump+WBI), lumpectomy plus brachytherapy, mastectomy alone, mastectomy plus reconstruction, and, in older women, lumpectomy alone. We performed a comparative examination of each treatment's complications and cost to assess their relative values. Methods: Using the MarketScan database of younger women with private insurance and the SEER-Medicare database of older women with public insurance, we identified 105 211 women with early breast cancer diagnosed between 2000 and 2011. We used diagnosis and procedural codes to identify treatment complications within 24 months of diagnosis and compared complications by treatment using two-sided logistic regression. Mean total and complication-related cost, relative to Lump+WBI, were calculated from a payer's perspective and adjusted for differences in covariables using linear regression. All statistical tests were two-sided. Results: Lump+WBI was the most commonly used treatment. Mastectomy plus reconstruction was associated with nearly twice the complication risk of Lump+WBI (Marketscan: 54.3% vs 29.6%, relative risk [RR] = 1.87, 95% confidence interval [CI] = 1.82 to 1.91, P < .001; SEER-Medicare: 66.1% vs 37.6%, RR = 1.75, 95% CI = 1.69 to 1.82, P < .001) and was also associated with higher adjusted total cost (Marketscan: $22 481 greater than Lump+WBI; SEER-Medicare: $1748 greater) and complication-related cost (Marketscan: $9017 greater; SEER-Medicare: $2092 greater). Brachytherapy had modestly higher total cost and complications than WBI. Lumpectomy alone entailed lower cost and complications in the SEER-Medicare cohort only. Conclusions: Mastectomy plus reconstruction results in substantially higher complications and cost than other guideline-concordant treatment options for early breast cancer. These findings are relevant to patients evaluating their local therapy options and to value-based population health management. PMID- 27678204 TI - Women with epilepsy. PMID- 27678205 TI - Women with epilepsy: clinically relevant issues. AB - Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population. PMID- 27678206 TI - Clinical and genetic investigation of a Brazilian family with Huntington's disease. AB - The aim of this study was to investigate a Brazilian family carrying full penetrance alleles for Huntington's disease (HD) in order to correlate each member's genetic and clinical features. To this end, the following scales were administered in each patient: the Beck Depression Inventory, the Mini-Mental State Examination (MMSE) and the Unified Huntington's Disease Rating Scale (UHDRS). The patterns of CAG and CCG polymorphic regions in the HTT gene were determined, the disease burden score was calculated, and genotypes were correlated with phenotypes within this family. We suggest that HD duration, the number of years of formal education, and UHDRS status variables can explain 96.6% of the MMSE variability in HD patients. A strong significant correlation was found between the disease burden score and the UHDRS (r = 0.76; p-value = 0.049) and the MMSE (r = -0.90; p-value = 0.006). The correlations between CAG allele size and the three clinical evaluations performed in the HD patients were not statistically significant. PMID- 27678207 TI - Spectrum of cognitive disorders in idiopathic normal pressure hydrocephalus. AB - Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by ventricular dilation accompanied by a progressive triad of a gait disturbance, "dementia" and incontinence. We retrospectively evaluated cognitive profile, and its relationship with disease variables, in 64 iNPH patients. The iNPH group performed significantly worse than the control group on all neuropsychological tests, except for verbal memory (within the normal range). The patients were subdivided into four groups: group 1 (42%: global cognitive impairment); group 2 (24%: frontosubcortical dysfunction); group 3 (17%: isolated deficit of a single cognitive domain); group 4 (17%: no cognitive impairment). Group 1 was older, with a significantly longer disease duration and more severe motor disease, while groups 3 and 4 were younger and presented milder motor impairment and a shorter disease duration. These data suggest parallel progression of cognitive and motor impairment in iNPH; early shunt surgery might prevent the development, in older age, of dementia in these patients. PMID- 27678208 TI - New test of odor pleasantness in Parkinson's disease. AB - The New Test of Odor Pleasantness (NTOP) evaluates the hedonicity of olfactory stimulants. The aim of this study was to compare results of the NTOP, the Sniffin' Sticks test, and the Odorized Marker Test (OMT) in patients with Parkinson's disease (PD). The study sample comprised 30 PD patients (mean age 71+/-7.36 years) and the control group made up of 31 non-PD subjects (mean age 68+/-12.39 years). Sociodemographic data, medical history and tests of cognitive function were investigated. Olfaction was evaluated using the NTOP, Sniffin' Sticks test and OMT. The PD patients, compared with the control group, recorded significantly lower scores on all three tests: NTOP (p=0.00), Sniffin' Sticks (p=0.02), OMT (p=0.00). The NTOP was the test preferred by 55% of the subjects. This preference was more marked in the PD group. This study shows that the NTOP is a valuable method within the complex array of olfactory screening tools used in PD. PMID- 27678210 TI - Robot-assisted gait training versus treadmill training in patients with Parkinson's disease: a kinematic evaluation with gait profile score. AB - The purpose of this study was to quantitatively compare the effects, on walking performance, of end-effector robotic rehabilitation locomotor training versus intensive training with a treadmill in Parkinson's disease (PD). Fifty patients with PD were randomly divided into two groups: 25 were assigned to the robot assisted therapy group (RG) and 25 to the intensive treadmill therapy group (IG). They were evaluated with clinical examination and 3D quantitative gait analysis [gait profile score (GPS) and its constituent gait variable scores (GVSs) were calculated from gait analysis data] at the beginning (T0) and at the end (T1) of the treatment. In the RG no differences were found in the GPS, but there were significant improvements in some GVSs (Pelvic Obl and Hip Ab-Add). The IG showed no statistically significant changes in either GPS or GVSs. The end-effector robotic rehabilitation locomotor training improved gait kinematics and seems to be effective for rehabilitation in patients with mild PD. PMID- 27678209 TI - Incidence and predictors of stroke during the index event in an ethnically diverse Takotsubo cardiomyopathy population. AB - Takotsubo cardiomyopathy (TTS) is a peculiar clinical condition often affecting postmenopausal women after a stressful trigger. The underlying mechanisms have not been completely elucidated but several hypotheses have been advanced, with catecholamine cardiotoxicity, microvascular dysfunction and coronary artery spasm each suggested to play a role. The incidence of stroke after TTS appears to range from 0% to 7.7%, and interestingly TTS has been described as both a cause and a complication of stroke. We sought to assess the incidence and predictors of stroke during the index event (peri-index event stroke) in a heterogeneous TTS population. We conducted a retrospective descriptive study reviewing patients who were discharged with a diagnosis of TTS from the Einstein Medical Center, Philadelphia, PA and Danbury Hospital, Danbury, CT in the period between 2003 and 2014. A total of Incidence and predictors of stroke during the index event in an ethnically diverse Takotsubo cardiomyopathy population 206 patients met the modified Mayo Clinic criteria and were included in the study. The patients' overall mean age was 67.8 years; 87% (n=179) were females and 25% (n=53) were African Americans. The following incidence rates were found: stroke 7%, in hospital heart failure 26.7%, and in-hospital death 7%. On multivariate analysis independent predictors (expressed as odds ratios with 95% confidence intervals) of periindex event stroke were: i) African American race (OR 3.2, 95% CI 1.2 10.2, p=0.048); ii) hypertension (OR 10.5, 95% CI 1.3-88, p=0.03). ACE inhibitor use was a protective factor for developing peri-index event stroke (OR 0.15, 95% CI 0.04-0.5, p=0.001). There was a trend towards dual antiplatelet therapy (DAPT) being protective for stroke (OR 0.3, 95% CI 0.05-1.1, p=0.08). The incidence of peri-index event stroke was 7%. African American race and hypertension were found to be independent predictors of peri-index event stroke. Prospective clinical trials are needed to confirm these findings and to better determine the impact of hypertension as a risk factor for stroke and to assess the role of DAPT in preventing it. PMID- 27678211 TI - Frailty and resilience in an older population. The role of resilience during rehabilitation after orthopedic surgery in geriatric patients with multiple comorbidities. AB - Hip fracture is common in the elderly and it is usually associated with comorbidities and physiological changes which may have an impact on functioning and quality of life. The concept of resilience may explain why this impact varies among patients. The aim of this open, prospective cohort study was to explore the relationships between resilience, frailty and quality of life in orthopedic rehabilitation patients, and also to assess whether these factors might affect rehabilitation outcome. Eighty-one patients, older than 60 years, underwent a multidisciplinary assessment at the beginning and at the end of the rehabilitation period following orthopedic surgery to the lower limb. The assessments were performed using the Resilience Scale, the Multidimensional Prognostic Index (as a measure of frailty), the WHO Quality of Life-BRIEF, the Geriatric Depression Scale, and the Functional Independence Frailty and resilience in an older population. The role of resilience during rehabilitation after orthopedic surgery in geriatric patients with multiple comorbidities Measure (as a measure of the rehabilitation outcome). A negative correlation between disability and resilience emerged and this association interacted with frailty level. We also found that resilience and quality of life are positive predictors of functional status at discharge. PMID- 27678212 TI - Post-stroke spasticity as a condition: a new perspective on patient evaluation. PMID- 27678213 TI - What is cluster headache? Fact sheet for patients and their families. A publication to mark Cluster Headache Day 2016. PMID- 27678214 TI - An efficient method for protein function annotation based on multilayer protein networks. AB - BACKGROUND: Accurate annotation of protein functions is still a big challenge for understanding life in the post-genomic era. Many computational methods based on protein-protein interaction (PPI) networks have been proposed to predict the function of proteins. However, the precision of these predictions still needs to be improved, due to the incompletion and noise in PPI networks. Integrating network topology and biological information could improve the accuracy of protein function prediction and may also lead to the discovery of multiple interaction types between proteins. Current algorithms generate a single network, which is archived using a weighted sum of all types of protein interactions. METHOD: The influences of different types of interactions on the prediction of protein functions are not the same. To address this, we construct multilayer protein networks (MPN) by integrating PPI networks, the domain of proteins, and information on protein complexes. In the MPN, there is more than one type of connections between pairwise proteins. Different types of connections reflect different roles and importance in protein function prediction. Based on the MPN, we propose a new protein function prediction method, named function prediction based on multilayer protein networks (FP-MPN). Given an un-annotated protein, the FP-MPN method visits each layer of the MPN in turn and generates a set of candidate neighbors with known functions. A set of predicted functions for the testing protein is then formed and all of these functions are scored and sorted. Each layer plays different importance on the prediction of protein functions. A number of top-ranking functions are selected to annotate the unknown protein. CONCLUSIONS: The method proposed in this paper was a better predictor when used on Saccharomyces cerevisiae protein data than other function prediction methods previously used. The proposed FP-MPN method takes different roles of connections in protein function prediction into account to reduce the artificial noise by introducing biological information. PMID- 27678215 TI - Mitochondrial Genome of Prasinophyte Alga Pyramimonas parkeae. AB - Prasinophytes are a paraphyletic assemblage of nine heterogeneous lineages in the Chlorophyta clade of Archaeplastida. Until now, seven complete mitochondrial genomes have been sequenced from four prasinophyte lineages. Here, we report the mitochondrial genome of Pyramimonas parkeae, the first representative of the prasinophyte clade I. The circular-mapping molecule is 43,294 bp long, AT rich (68.8%), very compact and it comprises two 6,671 bp long inverted repeat regions. The gene content is slightly smaller than the gene-richest prasinophyte mitochondrial genomes. The single identified intron is located in the cytochrome c oxidase subunit 1 gene (cox1). Interestingly, two exons of cox1 are encoded on the same strand of DNA in the reverse order and the mature mRNA is formed by trans-splicing. The phylogenetic analysis using the data set of 6,037 positions assembled from 34 mtDNA-encoded proteins of 48 green algae and plants is not in compliance with the branching order of prasinophyte clades revealed on the basis of 18S rRNA genes and cpDNA-encoded proteins. However, the phylogenetic analyses based on all three genomic elements support the sister position of prasinophyte clades Pyramimonadales and Mamiellales. PMID- 27678217 TI - Puberty in female wild boar (Sus scrofa) in Sweden. AB - BACKGROUND: Since the re-appearance of wild boars in Sweden in the 1970s, the population has increased. Besides having large litter sizes, puberty at an early age is considered as an important factor contributing to the high reproductive potential of wild boar. Although controversial, supplemental feeding is applied to varying extent throughout the wild boar range in Sweden, and its effect on wild boar reproduction is debated. The aim of this study was to investigate the proportion of post-pubertal female wild boar gilts in a population subjected to supplemental feeding, in relation to age, weight, and season. Also, the effect of another definition of puberty (based upon follicular size) on the outcome of the proportion of female wild boar gilts considered to be able to reproduce in a population was illustrated. Between Jan 2013 and Dec 2015 reproductive organs from 592 female wild boars, were collected. Ovaries and uterus were macroscopically examined, and reproductive stage was determined by the presence of ovarian structures and uterus characteristics. Age was estimated using tooth eruption and tooth replacement, and weight was noted. A subset of 175 female wild boars, aged 5-15 months, was included in this study. An animal was considered to be post-pubertal if the ovaries contained one or more corpora lutea (CL) or if the uterus showed signs of previous pregnancy (presence of enlarged blood vessels in the cut surface between the mesometric ligament and the uterus). RESULTS: In total, 29 (16.6 %) animals were classified as post-pubertal. Field dressed weight ranged from 20.6 to 65.3 kg. Season, weight, and age class significantly influenced the variation in proportion of post-pubertal females. Post-pubertal animals were found in autumn, winter, and spring, but not in the summer season. Another definition of puberty, based on follicle size, lead to different result on proportions of animals considered to have passed puberty. CONCLUSIONS: Season, weight, and age significantly influenced the variation in proportion of post pubertal wild boar females. The proportion of post-pubertal animals increased with age and weight. However, weight is probably a better proxy for puberty than age group is. The proportion of post-pubertal females also increased from summer to spring suggesting a seasonal reproductive pattern. Different definitions of puberty will result in various outcomes, which high-lights the importance of using adequate definition of puberty. PMID- 27678218 TI - How to quantify the temporal storage effect using simulations instead of math. AB - The storage effect has become a core concept in community ecology, explaining how environmental fluctuations can promote coexistence and maintain biodiversity. However, limitations of existing theory have hindered empirical applications: the need for detailed mathematical analysis whenever the study system requires a new model, and restricted theory for structured populations. We present a new approach that overcomes both these limitations. We show how temporal storage effect can be quantified by Monte Carlo simulations in a wide range of models for competing species. We use the lottery model and a generic integral projection model (IPM) to introduce ideas, and present two empirical applications: (1) algal species in a chemostat with variable temperature, showing that the storage effect can operate without a long-lived life stage and (2) a sagebrush steppe community IPM. Our results highlight the need for careful modelling of nonlinearities so that conclusions are not driven by unrecognised model constraints. PMID- 27678216 TI - Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index. AB - BACKGROUND: Novel direct antiviral agents (DAA) targeting hepatitis C virus (HCV) have revolutionized the treatment of chronic hepatitis C infection (CHC). Rates of sustained virological response (SVR) to treatment have drastically improved since introduction of DAA. Transient Elastography (TE) is an ultrasound based, non-invasive technique to assess liver stiffness (LS). We examined the changes in TE values and fibrosis scores FIB-4 and APRI after DAA treatment of CHC. METHODS: 549 patients who received a DAA based treatment for CHC were screened and 392 were included. TE values recorded prior to therapy and within 18 months after therapy were evaluated. In addition, FIB-4 and APRI scores were calculated and histopathological results were recorded if available. RESULTS: Median TE prior to DAA treatment was 12.65 kPa (IQR 9.45-19.2 kPa) and decreased to 8.55 kPa (IQR 5.93-15.25) post-treatment. This finding is statistically significant (P<.001) and equals a TE regression of 32.4% after DAA treatment. Median FIB-4 and APRI values significantly decreased from 2.54 (IQR 1.65-4.43) and 1.10 (IQR 0.65-2.43) to 1.80 (IQR 1.23-2.84, P<.001) and 0.43 (IQR 0.3-0.79, P<.001) respectively. CONCLUSION: Patients with SVR after DAA therapy showed significant regression of TE values. Rapid decrease in TE was in concordance with regression of validated fibrosis scores FIB-4 and APRI. It remains to be examined whether this indicates a true regression of fibrosis or merely resolution of chronic liver inflammation with subsequent improvement of TE values and laboratory parameters. PMID- 27678220 TI - Human IL-22 binding protein isoforms act as a rheostat for IL-22 signaling. AB - The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue homeostasis and immunosurveillance. Dysregulation of IL-22 signaling causes inflammatory diseases. IL-22 binding protein (IL-22BP; encoded by IL22RA2) is a soluble IL-22 receptor, which antagonizes IL-22 activity and has genetic associations with autoimmune diseases. Humans have three IL-22BP isoforms, IL 22BPi1 to IL-22BPi3, which are generated by alternative splicing; mice only have an IL-22BPi2 homolog. We showed that, although IL-22BPi3 had less inhibitory activity than IL-22BPi2, IL-22BPi3 was more abundant in various human tissues under homeostatic conditions. IL-22BPi2 was more effective than IL-22BPi3 at blocking the contribution of IL-22 to cooperative gene induction with the inflammatory cytokine IL-17, which is often present with IL-22 in autoimmune settings. In addition, we found that IL-22BPi1 was not secreted and therefore failed to antagonize IL-22 signaling. Furthermore, IL-22BPi2 was the only isoform that was increased in abundance when myeloid cells were activated by Toll-like receptor 2 signaling or retinoic acid, a maturation factor for myeloid cells. These data suggest that the human IL-22BP isoforms have distinct spatial and temporal roles and coordinately fine-tune IL-22-dependent STAT3 responses in tissues as a type of rheostat. PMID- 27678219 TI - Bypassing STAT3-mediated inhibition of the transcriptional regulator ID2 improves the antitumor efficacy of dendritic cells. AB - Despite the potent ability of dendritic cells (DCs) to stimulate lymphocyte responses and host immunity, granulocyte-macrophage colony-stimulating factor derived DCs (GM-DCs) used as antitumor vaccines have demonstrated relatively modest success in cancer immunotherapy. We found that injecting GM-DCs into melanoma tumors in mice, or culturing GM-DCs with melanoma-secreted cytokines or melanoma-conditioned medium, rapidly suppressed DC-intrinsic expression of the gene encoding inhibitor of differentiation 2 (ID2), a transcriptional regulator. Melanoma-associated cytokines repressed Id2 transcription in murine DCs through the activation of signal transducer and activator of transcription 3 (STAT3). Enforced expression of ID2 in GM-DCs (ID2-GM-DCs) suppressed their production of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Vaccination with ID2-GM-DCs slowed the progression of melanoma tumors and enhanced animal survival, which was associated with an increased abundance of tumor-infiltrating interferon-gamma-positive CD4(+) effector and CD8(+) cytotoxic T cells and a decreased number of tumor-infiltrating regulatory CD4(+) T cells. The efficacy of the ID2-GM-DC vaccine was improved by combinatorial treatment with a blocking antibody to programmed cell death protein-1 (PD-1), a current immunotherapy that overcomes suppressive immune checkpoint signaling. Collectively, our data reveal a previously unrecognized STAT3-mediated immunosuppressive mechanism in DCs and indicate that DC-intrinsic ID2 promotes tumor immunity by modulating tumor associated CD4(+) T cell responses. Thus, inhibiting STAT3 or overexpressing ID2 selectively in DCs may improve the efficiency of DC vaccines in cancer therapy. PMID- 27678222 TI - Dependence: a strange but important outlier in personality disorders. PMID- 27678221 TI - The NF-kappaB subunit RelB controls p100 processing by competing with the kinases NIK and IKK1 for binding to p100. AB - The heterodimer formed by the nuclear factor kappaB (NF-kappaB) subunits p52 and RelB is the product of noncanonical signaling in which the key event is the proteolytic processing of p100 to generate p52. The kinases NF-kappaB-inducing kinase (NIK) and inhibitor of kappaB kinase 1 (IKK1; also known as IKKalpha) are activated during noncanonical signaling and play essential roles in p100 processing. In resting cells, RelB remains associated with unprocessed p100 as a transcriptionally inert p100:RelB complex, which is part of a larger assembly with other NF-kappaB factors known as the "kappaBsome." We investigated how these two different RelB-containing complexes with opposing effects on target gene transcription are formed. We found that RelB controls the extent of both p100 processing and kappaBsome formation during noncanonical signaling. Within an apparently "transitional" complex that contains RelB, NIK, IKK1, and p100, RelB and the NIK:IKK1 complex competed with each other for binding to a region of p100. A fraction of p100 in the transitional complex was refractory to processing, which resulted in the formation of the kappaBsome. However, another fraction of p100 protein underwent NIK:IKK1-mediated phosphorylation and processing while remaining bound to RelB, thus forming the p52:RelB heterodimer. Our results suggest that changes in the relative concentrations of RelB, NIK:IKK1, and p100 during noncanonical signaling modulate this transitional complex and are critical for maintaining the fine balance between the processing and protection of p100. PMID- 27678223 TI - Odontome: A Brief Overview. AB - Odontomas are the most common type of odontogenic tumors. They are included under the benign calcified odontogenic tumors. Odontomas are basically classified into two types, complex and compound odontomes. Various theories or etiological factors are been quoted for the occurrence of odontomes. Generally, they are asymptomatic. Occasionally, signs and symptoms relating to their presence do occur. The sole management depends upon the early diagnosis, histopathological examination and excision of these tissues. This article briefs regarding its classification, etiological factors, occurrence, differences between complex and compound odontomes, diagnosis and management. PMID- 27678224 TI - Can We Tune Our Pediatric Patients? AB - For the pedodontic team, a child's dental anxiety poses major management problems. Previously, wide variety of aversive techniques have been used with varying success rates to manage anxious child patients. The present trend advocates the use of nonaversive techniques like distraction in the management of anxious pediatric patients. So the aim of this study is to compare the effect of audio distraction with the normal set up operatory. Thirty patients of age between 4 and 8 years were included in the study. Each patient had gone through four dental visits. Anxiety was measured using Venham's picture test. The values obtained were tabulated and statistical analysis and concluded that audio distraction did decrease the level of anxiety in anxious pediatric dental patients to a significant level during the restorative procedure visit (3rd) and invasive procedure visit (4th). PMID- 27678225 TI - Comparative Evaluation of 0.2 percent Chlorhexidine and Magnetized Water as a Mouth Rinse on Streptococcus mutans in Children. AB - Chlorhexidine (0.2%) is a 'Gold Standard' which is commercially available and effective mouth rinse which inhibits supragingival plaque formation and also reduction in the population of S. mutans after rinsing daily. Lately, it has been proved that the force of magnetism has a great influence on the living organism. Magnetized water has its effect on human body when taken regularly for a considerable period but its use in dentistry is still lacking. AIM: This study was done to evaluate antibacterial efficacy and effect of dosage, frequency and duration of commercially available 0.2% chlorhexidine mouth rinse and conventionally prepared magnetized water on colony count of S. mutans. MATERIALS AND METHODS: A total of 50 subjects were selected between the age group of 5 to 12 years. A baseline sample was collected before starting with rinses. Then the subjects were divided in four major groups. Group I was chlorhexidine, group II was subdivided into group IIA and group IIB which were magnetized water groups (24 hours of magnetization) rinsing for 1 minute and 3 minutes respectively and group III was magnetized water (72 hours of magnetization) group rinsing for 3 minutes. The samples were collected and sent to microbiological laboratory for S. mutans count. RESULTS: The obtained values of all the groups were subjected to statistical analysis. CONCLUSION: The reduction of S. mutans count of group III was almost in par with group I. PMID- 27678226 TI - Comparative Evaluation of the Adhesive Properties of Two Generations of Dentin Bonding Agents by Checking the Microleakage in the Primary Teeth: An in vitro Study. AB - Early childhood caries is now affecting the children in dangerous proportions. There is a widespread loss of the tooth material irrespective of the type of the carious lesion. Restoration of such lesions with a strong permanent bond between the dental tissues and the restorative dental materials would be a highly desirable requisite of any restorative material. Ultramorphological characterizations show that the interfa-cial morphology and the chemical characterization of the bonding systems appear to be strongly associated with each other and, therefore, observing and understanding the interfacial phenomenon and its quality would be of great importance in the selection of a dental adhesive for its use in pediatric restorative dentistry. PMID- 27678227 TI - Knowledge and Attitude of Primary School Teachers toward Tooth Avulsion and Dental First Aid in Davangere City: A Cross-sectional Survey. AB - AIM OF THE STUDY: Traumatic dental injuries including avulsed tooth is a tragic and ignored problem among school children. As children spend much of their time in schools, school teachers form the group who commonly supervise the physical activity of the children, so awareness about avulsed tooth emergency management among school teachers is an important concept for long-term success and to prevent its future consequences. The purpose of this study was to assess the knowledge and attitude regarding tooth avulsion and dental first aid among primary school teachers in Davangere city. METHODS: The study was performed by administering a self-designed questionnaire on a sample of 300 primary school teachers. RESULTS: Sixty-eight percent of the school teachers (government, semi aided and aided schools) admitted the possibility of an avulsed tooth to be replanted and thirty-two percent had no idea on tooth replantation and only twenty-three percent of the teachers knew the procedures taken in cases of avulsed teeth. Seventy-seven percent of all teachers did not feel the possibility of tooth replantation. CONCLUSION: There is poor knowledge in the management of avulsed teeth among the school teachers of Davangere city. They do not feel capable of replanting an avulsed tooth. As one of the child supervisors, all the school teachers should have the basic knowledge to recognize oral emergencies and regarding conservation of avulsed teeth to prevent its consequences in the child's future. PMID- 27678228 TI - Impacted Canines: Our Clinical Experience. AB - BACKGROUND: To discuss the management of impacted canines and the various approaches used for the same. MATERIALS AND METHODS: The data of 33 cases, with 43 impacted canine teeth, seen and operated over a period of 3-year in Santosh Dental College and Hospital has been compiled. The diagnostic methods and treatment modalities undertaken are described and discussed. RESULTS: Canine impactions were more common in the maxilla as compared with mandible in our study, which was statistically significant. Impacted canine position was mostly palatal in maxilla and labial in mandible. Chi-square test yielded a p-value of 0.002 which shows that there is an association between arch and position. The treatment options used were surgical exposure and orthodontic repositioning, cyst enucleation with extraction of impacted canine and surgical removal of impacted canine. CONCLUSION: Surgical exposure and orthodontic repositioning was successfully applied as first-line treatment for correcting ectopic positioned canine. In cases where exposure and subsequent orthodontic treatment was not indicated, the impacted canine was surgically removed to prevent future problems and surgical procedure was designed according to position of impacted canine. PMID- 27678230 TI - Apexum: A Minimum Invasive Procedure. AB - The new Apexum procedure (Apexum Ltd, Or-Yehuda, Israel) is based on a minimally invasive removal of periapical chronically inflamed tissues through a root canal access. Apexum procedure (a novel method that allows for the removal or debulking of periapical tissues without using scalpels, periosteal elevators, or sutures) results in significant less postoperative discomfort or pain than conventional root canal treatment or than reported for conventional apical surgery. The removal or debulking of the periapical inflamed tissues, using the Apexum procedure, seems to enhance healing kinetics with no adverse events. PMID- 27678229 TI - Comparison of the Reliability of Anatomic Landmarks based on PA Cephalometric Radiographs and 3D CT Scans in Patients with Facial Asymmetry. AB - INTRODUCTION: Conventional cephalometry is an inexpensive and well-established method for evaluating patients with dentofacial deformities. However, patients with major deformities and in particular asymmetric cases are difficult to evaluate by conventional cephalometry. Reliable and accurate evaluation in the orbital and midfacial region in craniofacial syndrome patients is difficult due to inherent geometric magnification, distortion and the superpositioning of the craniofacial structures on cephalograms. Both two- and three-dimensional computed tomography (CT) have been proposed to alleviate some of these difficulties. AIMS AND OBJECTIVES: The aim of our study is to compare the reliability of anatomic cephalometric points obtained from the two modalities: Conventional posteroanterior cephalograms and 3D CT of patients with facial asymmetry, by comparison of intra- and interobserver variation of points recorded from frontal X-ray to those recorded from 3D CT. MATERIALS AND METHODS: The sample included nine patients (5 males and 4 females) with an age range of 14 to 21 years and a mean age of 17.11 years, whose treatment plan called for correction of facial asymmetry. All CT scans were measured twice by two investigators with 2 weeks separation for determination of intraobserver and interobserver variability. Similarly, all measurement points on the frontal cephalograms were traced twice with 2 weeks separation. The tracings were superimposed and the average distance between replicate points readings were used as a measure of intra- and interobserver reliability. Intra-and interobserver variations are calculated for each method and the data were imported directly into the statistical program, SPSS 10.0.1 for windows. RESULTS: Intraobserver variations of points defined on 3D CT were small compared with frontal cephalograms. The intraobserver variations ranged from 0 (A1, B1) to 0.6 mm with the variations less than 0.5 mm for most of the points. Interobserver variations of points between first and second tracings defined on PA Ceph and 3D CT were less than 1.5 mm for all the points. A direct comparison of frontal cephalometry and 3D CT using intraobserver variation for the first observer showed that 3D CT was more reliable than frontal cephalometry for 11 points. Direct comparison of frontal cephalometry and 3D CT for the second observer showed a similar tendency with 14 points significantly more reliable for 3D CT. Comparison of frontal cephalometry and 3D CT using interobserver variation for the tracings showed that 3D CT was more reliable than frontal cephalometry. SUMMARY AND CONCLUSION: The study has shown that 3D CT is consistently more accurate and reliable than conventional frontal cephalometry. Unfortunately, the cost of a computerized tomography examination is considerable; this means that, at this stage, its use by surgeons and orthodontists is a last resort. PMID- 27678231 TI - Delayed Replantation after Endodontic and Fluoride Treatment: A 5-Year Follow-up. AB - AIM: To evaluate if endodontic and fluoride treatment of the root before delayed replantation would render the tooth a favorable prognosis. METHODS: A 10-year-old boy reported 10 hours after he had avulsed his maxillary right permanent central incisor. The pulp and PDL cells were considered to be nonviable. Endodontic treatment for the tooth was performed extraorally and obturated with gutta percha. Prior to replantation, the root was treated with 1.23% APSF for 15 minutes. RESULT: An intraoral radiograph taken 6 months after replantation revealed narrowing of the PDL space around the replanted tooth due to apposition from the surrounding alveolar bone. A radiograph taken 5 years after replantation revealed no evidence of external root resorption. There was no abnormal mobility either. CONCLUSION: Extraoral endodontic treatment and root treatment with 1.23% APSF prior to delayed replantation might prevent the occurrence of external root resorption. PMID- 27678232 TI - Osteopetrosis (Marble Bone Disease): A Rare Disease in Children. AB - Osteopetrosis is a group of diseases that affects the growth and remodeling of bone and characterized by over growth and sclerosis of bone, with thickening of the bony cortices, abnormal dental development and narrowing of the marrow cavities throughout the skeleton. It is an uncommon disease of unknown cause. A 5 year-old boy was suffering from infantile (severe form) osteopetrosis with cardiac enlargement, severe anemia, hepatosplenomagaly and radiographs showed generalized increase in bone density (chalky white), narrowing of skull base is reported here. PMID- 27678233 TI - Treacher Collins Syndrome: A Case Report and a Brief Review on Diagnostic Aids. AB - Treacher Collins syndrome (Mandibulofacial dysostosis) is characterized by deafness, hypoplasia of facial bones (mandible, maxilla and cheek bone), antimongoloid slant of palpebral fissures, coloboma of the lower lid and bilateral anomalies of the auricle. Hypoplasia of the facial bones may be the first indicator of the disorder. We present a case report of Treacher Collins syndrome with their extraoral findings, intraoral findings and their treatment plan. We have also included the various etiological factors, clinical diagnostic aids, and multidisciplinary team approach. PMID- 27678234 TI - Oral Teratoma with a Primitive Neuroectodermal Tumor Component: A Case Report. AB - Teratomas are tumors of germ cell derivation consist of tissues derived from all the three germ cell layers. They comprise the most common extragonadal germ cell tumors (EGCT) in childhood. EGCTs of head and neck region account for only 5% of all benign and malignant germ cell tumors and for 6% of all teratomas. Primitive neuroectodermal tumor (PNET) arising from germ cell tumor is a distinct entity. It develops from the malignant transformation of teratomas along ectodermal lines. This paper presents a rare case of oral teratoma in a 6-year-old male who reported with pain and swelling in the right upper back teeth region of jaw. Under light microscopy, mature and immature structures representatives of trilineage derivatives were appreciated. Sheets of small round cells showing vague rosette and membranous positivity to CD-99 directed us to consider the above diagnosis. PMID- 27678235 TI - Amelogenesis Imperfecta with Anterior Open Bite: A Rare Case Report. AB - This clinical report describes the treatment plan for a young patient affected by amelogenesis imperfecta with anterior open bite. The objectives of the treatment were to eliminate tooth sensitivity while enhancing esthetics and restoring masticatory function. Treatment included resin composite laminate veneers on maxillary anterior teeth and stainless steel crowns for posterior teeth. PMID- 27678236 TI - Myiasis of Maxilla: Report of a Case. AB - Oral myiasis is a disease caused by larvae of housefly and associated with poor oral hygiene, mouth breathing and incompetent lips. The disease is characterized by presence of maggots in affected parts of the body and is usually seen in tropical countries, although cases have been reported from other parts of the world. There are various methods for treating this disease. In this case report, a combination of treatment modalities has been favored. PMID- 27678237 TI - Interceptive Orthodontics and Growth Modification Therapy with Fixed Functional Appliance: A Case Report. AB - A 12-year-old female patient presented with proclined upper anteriors on a class II skeletal base, a retrognathic mandible and high maxillary- mandibular plane angle. Lower first molars were mesially tipped and lower second premolars were impacted. Treatment plan included uprighting and distalising the lower molars followed by growth modulation with Jasper Jumper to correct the mandibular retrognathism. Final finishing and detailing of occlusion was carried out through 0.022" MBT prescription preadjusted edgewise appliance therapy. PMID- 27678238 TI - Management of Delayed Eruption of Permanent Maxillary Incisor associated with the Presence of Supernumerary Teeth: A Case Report. AB - A supernumerary tooth is one that is additional to the normal series and can be found in almost any region of the dental arch. Clinically, supernumerary teeth are able to cause different local disorders. It is important for the dentist to be aware of the clinical complications of supernumerary teeth, the most common being the delayed eruption of permanent teeth. Early diagnosis and management of supernumerary teeth is important to prevent the need for more complex surgical and orthodontic treatment. This case report highlights the problem of delayed eruption of permanent maxillary left central incisor in a 9-year-old boy due to two supernumerary teeth, one tuberculate type and other impacted inverted mesiodens. PMID- 27678239 TI - Single Step Endodontic Management of Immature Apices using MTA. AB - AIM: To examine the clinical and radiographic appearance of teeth with immature apices that were treated by single step procedure using mineral trioxide aggregate (MTA). SUMMARY: Creation of a physiological hard tissue barrier with calcium hydroxide in a nonvital tooth although quite predictable has certain limitations, such as the very long duration of the treatment spread over multiple visits and increased risk of root fracture. Plugging the root canal end with MTA has been advocated as an alternative treatment modality for open apices. The technique has been proven to be successful in many recently reported cases. The cases reported here present the successful treatment of two traumatized maxillary central incisors with open apices and periapical lesions using MTA. In this case report, MTA has been used to create a hard tissue barrier after disinfection of the root canal. PMID- 27678240 TI - Odontogenic Myxoma of the Maxilla: A Report of Unusual Pediatric Case. AB - Odontogenic myxoma (OM) is a rare and locally benign neoplasm of high aggressive behavior found exclusively in the jaws. OM commonly occurs in the second and third decade, its quite rare to find in maxilla that to invading the maxillary sinus completely. The lesion often grows without symptoms and presents as a painless swelling. The radiographic features are variable, and the diagnosis is therefore not easy. This article presents a case of OM of maxilla in a 13-year old boy, which was previously diagnosed as fibrosseous lesion with the help of CT. PMID- 27678241 TI - Ectodermal Dysplasia: A Case Report. AB - Ectodermal dysplasia is a hereditary disease characterized by dysplasia of tissues of ectodermal origin. The incidence of ectodermal dysplasia is rare (1 in 100,000 birth). This case report discusses the features, classification and prosthetic treatment plan (upper partial denture and lower complete denture for upper partial and lower complete edentulous arches respectively). This treatment plan would be able to provide psychological and functional boost to the sufferer. PMID- 27678242 TI - Editorial. PMID- 27678243 TI - Racial/Ethnic Differences in the Use of Complementary and Alternative Medicine in US Adults With Moderate Mental Distress. AB - OBJECTIVES: To examine the prevalence of complementary and alternative medicine (CAM) use by race/ethnicity and to identify sociodemographic and health-related factors associated with CAM use among US adults with moderate mental distress (MMD). METHODS: We analyzed data from the 2012 National Health Interview Survey (NHIS). We used data for 6016 noninstitutionalized US adults with MMD (3492 non Hispanic whites, 953 non-Hispanic blacks, 1078 Hispanics, 268 Asians, and 225 others consisted of American Indian, Alaska Native, and those reporting multiple races). The 2012 NHIS asks about 36 types of CAM use in the past 12 months. We constructed (1) overall, any CAM use; (2) 5 major types of CAM use; and (3) individual types of CAM use indicators. Using a cross-sectional design with complex survey techniques, we estimated race/ethnicity-specific CAM prevalence, and odds of past year CAM use by race/ethnicity, sociodemographic, and health related factors. RESULTS: Nearly 40% of adults with MMD used CAM in the past year compared with 32% of those without MMD ( P < .001). In adults with MMD, past year CAM use differed by race/ethnicity, ranging from 24.3% (blacks) to 44.7% (Asians) and 46.8% (others) ( P < .001). Being younger, female, living in the west, higher education, being employed, more than 4 ambulatory care visits, and functional limitations were associated with higher odds of CAM use ( P < .01). CONCLUSIONS: Adults with MMD use CAM more frequently than those without MMD. In addition, CAM use was significantly differed by race/ethnicity in adults with MMD. This underscores the need for good patient-provider communication and suggests opportunity for dialogue about integration between conventional providers and CAM practitioners to facilitate optimal mental health care. PMID- 27678244 TI - Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection. AB - BACKGROUND: Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia. Pneumococcal infection is initiated by bacterial adherence to lung epithelial cells. The exact transcriptional changes occurring in both host and microbe during infection are unknown. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells by S. pneumoniae and assess the resulting transcriptome changes in both organisms simultaneously by using dual RNA-seq. RESULTS: Functional analysis of the time-resolved dual RNA seq data identifies several features of pneumococcal infection. For instance, we show that the glutathione-dependent reactive oxygen detoxification pathway in epithelial cells is activated by reactive oxygen species produced by S. pneumoniae. Addition of the antioxidant resveratrol during infection abates this response. At the same time, pneumococci activate the competence regulon during co incubation with lung epithelial cells. By comparing transcriptional changes between wild-type encapsulated and mutant unencapsulated pneumococci, we demonstrate that adherent pneumococci, but not free-floating bacteria, repress innate immune responses in epithelial cells including expression of the chemokine IL-8 and the production of antimicrobial peptides. We also show that pneumococci activate several sugar transporters in response to adherence to epithelial cells and demonstrate that this activation depends on host-derived mucins. CONCLUSIONS: We provide a dual-transcriptomics overview of early pneumococcal infection in a time-resolved manner, providing new insights into host-microbe interactions. To allow easy access to the data by the community, a web-based platform was developed ( http://dualrnaseq.molgenrug.nl ). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies. PMID- 27678245 TI - Identifying spatial imaging biomarkers of glioblastoma multiforme for survival group prediction. AB - PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Most GBMs exhibit extensive regional heterogeneity at tissue, cellular, and molecular scales, but the clinical relevance of the observed spatial imaging characteristics remains unknown. We investigated pretreatment magnetic resonance imaging (MRI) scans of GBMs to identify tumor subregions and quantify their image-based spatial characteristics that are associated with survival time. MATERIALS AND METHODS: We quantified tumor subregions (termed habitats) in GBMs, which are hypothesized to capture intratumoral characteristics using multiple MRI sequences. For proof-of-concept, we developed a computational framework that used intratumoral grouping and spatial mapping to identify GBM tumor subregions and yield habitat-based features. Using a feature selector and three classifiers, experimental results from two datasets are reported, including Dataset1 with 32 GBM patients (594 tumor slices) and Dataset2 with 22 GBM patients, who did not undergo resection (261 tumor slices) for survival group prediction. RESULTS: In both datasets, we show that habitat-based features achieved 87.50% and 86.36% accuracies for survival group prediction, respectively, using leave-one-out cross-validation. Experimental results revealed that spatially correlated features between signal-enhanced subregions were effective for predicting survival groups (P < 0.05 for all three machine-learning classifiers). CONCLUSION: The quantitative spatial-correlated features derived from MRI-defined tumor subregions in GBM could be effectively used to predict the survival time of patients. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;46:115-123. PMID- 27678247 TI - Ocular Drug Delivery through pHEMA-Hydrogel Contact Lenses Co-Loaded with Lipophilic Vitamins. AB - Ocular drug delivery through hydrogel contact lenses has great potential for the treatment of ocular diseases. Previous studies showed that the loading of lipophilic vitamin E to silicone-hydrogel contact lenses was beneficial in ocular drug delivery. We hypothesized that vitamin E loading to another type of popular hydrogel contact lenses, pHEMA-hydrogel contact lenses, improves ocular drug delivery by increasing the drug loading or the duration of drug release. Loading of vitamin E to pHEMA-hydrogel contact lenses significantly increased the loading of a hydrophilic drug surrogate (Alexa Fluor 488 dye) and two hydrophilic glaucoma drugs (timolol and brimonidine) to the lenses by 37.5%, 19.1%, and 18.7%, respectively. However, the release duration time was not significantly altered. Next, we hypothesized that the lipophilic nature of vitamin E attributes to the enhanced drug loading. Therefore, we investigated the effects of co loading of another lipophilic vitamin, vitamin A, on drug surrogate delivery. We found out that vitamin A loading also increased the loading of the drug surrogate to pHEMA-hydrogel contact lenses by 30.3%. Similar to vitamin E loading, vitamin A loading did not significantly alter the release duration time of the drug or drug surrogate. PMID- 27678248 TI - Are there gender differences in wellbeing related to work status among persons with severe impairments? AB - AIM: The aim of this study was to analyse gender differences in wellbeing, as related to work status, among working-age people with severe impairments. METHODS: This study is based on register and survey data for a sample of 7298 persons, drawn from the entire Swedish population of 15,515 working-age people 16 64 years old who, at the end of 2010, received Sweden's unique personal assistance allowance, an allowance paid from the Swedish Social Insurance Agency (SSIA) to persons with severe impairments, enabling them to pay for assistants to support them in the functions of daily life. Logistic regression models were used to estimate the strength of relations between six measures of wellbeing, work status (not working, irregular work and regular work) and gender, together with key confounders. RESULTS: Of the persons surveyed, 21% responded that they had regular work. Gender differences were found for all confounders, except for age. They were mostly in favour of men, which could reflect the general pattern in the labour market at large. Our results indicated there are substantial differences between non-working, irregularly working and working persons for several wellbeing aspects. CONCLUSIONS: This study analyses the contributions to wellbeing of work participation among working-age people with severe impairments, with a focus on gender differences. The analysis shows that work is an important determinant of the six measures of wellbeing examined, where the relationship between work participation and wellbeing is especially strong for peoples' perceived standard of living. This major finding holds for both genders; however, the data show gender imbalance, in that compared with women, there was a larger percentage of men with severe impairments who have regular work. Future research should focus on finer distinctions between the types of work and the value added of personal assistants in the work context. Measures of general health not available for this study are needed to filter out a clearer picture of the interaction of work and well-being. Despite drawbacks, this study is nevertheless path-breaking in its focus on the value of work participation for the well-being of persons with severe impairments. For this reason, it provides a valuable extension of our knowledge and a clear point of departure for future studies. PMID- 27678246 TI - Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer. AB - BACKGROUND: Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. CONCLUSIONS: A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy. PMID- 27678249 TI - Molecular characterization of GPR50 gene and study of its comparative genetic variability in sheep breeds adapted to different thermo-contrasting climatic regimens. AB - GPR50, formerly known as a melatonin-related receptor, is one of the three subtypes of melatonin receptor subfamily, together with MTNR1A and MTNR1B. GPR50, despite its high identity with the melatonin receptor family, does not bind melatonin and is considered to be an ortholog of MTNR1C in mammals. GPR50 expressing cells have been found in the dorsomedial nucleus of the hypothalamus, the periventricular nucleus, and the median eminence. Genetic and functional evidence have been recently investigated linking GPR50 to adaptive thermogenesis and torpor, but still, it is an orphan receptor and is yet to be studied conclusively. The aims of the study were to characterize the GPR50 gene of sheep and to study the sequence variability of the gene in Indian sheep breeds of two different thermo-varied agroclimatic conditions. Genomic DNA isolation was done and a 791-bp sequence was amplified using self-designed primers and SNP profiling done out of samples of all the breeds to study the relative frequency of SNPs in each of the breed. Five important non-synonymous mutations were observed in the various breeds studied. T698G, G1097A, G1270A, G1318A, and C1334G lead to the following substitution: valine by glycine, arginine by glutamine, threonine by alanine, isoleucine by valine, and serine by cytosine, respectively. Two synonymous mutations (T663G and C888T) were also observed in some of the studied breeds. G1270A and C888T were the most prevalent SNPs observed in nearly all of the breeds. C888T SNPs were observed in higher prevalence in Chokla, Marwari, and Magra in comparison to Gaddi and Bharat Merino. A PolyPhen-2 analysis, which is used to assess the potential damaging nature of an SNP, revealed that mutation T698G and G1270A were benign while G1097A, G1318A, and C1334G were damaging with a score of 0.987, 0.993, and 0.739, respectively. A 3-D homology model of the protein was prepared using c4zwjA (UniProt sequence ID) as a template using the online version of Phyre2 protein modeling software. The structure demonstrated closed similarity with other G-coupled receptor and it had a 45 % alpha-helical content. G1270A and C888T may be taken up for SNP correlation in a larger population study for their association with heat stress protection. PMID- 27678251 TI - Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers. AB - OBJECTIVE: For 'asymptomatic carriers' of the succinate dehydrogenase subunit B (SDHB) gene mutations, there is currently no consensus as to the appropriate modality or frequency of surveillance imaging. We present the results of a surveillance programme of SDHB mutation carriers. DESIGN: Review of clinical outcomes of a surveillance regimen in patients identified to have an SDHB gene mutation, based on annual MRI, in a single UK tertiary referral centre. PATIENTS: A total of 92 patients were identified with an SDHB gene mutation. a total of 27 index patients presented with symptoms, and 65 patients were identified as asymptomatic carriers. MEASUREMENTS: Annual MRI of the abdomen, with alternate year MRI of the neck, thorax and pelvis. Presence of an SDHB-related tumour included paraganglioma (PGL), phaeochromocytoma (PCC), renal cell carcinoma (RCC) and gastrointestinal stromal tumour (GIST). RESULTS: A total of 43 PGLs, eight PCCs and one RCC occurred in the 27 index patients (23 solitary, four synchronous, five metachronous). A further 15 SDHB-related tumours (11 PGLs, three RCCs, one GIST) were identified in the asymptomatic carriers on surveillance screening (25% of screened carriers): 10 on the first surveillance imaging and five on subsequent imaging 2-6 years later. A total of 11 patients had malignant disease. CONCLUSIONS: SDHB-related tumours are picked up as early as 2 years after initial negative surveillance scan. We believe the high malignancy rate and early identification rate of tumours justifies the use of 1-2 yearly imaging protocols and MRI-based imaging could form the mainstay of surveillance in this patient group thereby minimizing radiation exposure. PMID- 27678252 TI - Technical proficiency in cytopathology: assessment through external quality assurance. AB - OBJECTIVE: To assess both the feasibility and value of conducting an external quality assurance programme concerning technical aspects of cytopathology laboratory practice, and the interest by laboratories in enrolling in such a programme. METHODS: Six technical surveys, comprising staining exercises and questionnaires relating to laboratory practice, were distributed over a 4-year period to the approximately 220 laboratories enrolled in the RCPAQAP Cytopathology slide survey modules. Staining exercises using the Papanicolaou and Romanowsky techniques, the preparation of urine and body fluid specimens and immunocytochemistry on the cell block material were assessed. Accompanying relevant questionnaires were included, and one survey comprised a questionnaire alone concerning the collection of urinary tract and body fluid samples. RESULTS: Provision of an external cytopathology technical module was feasible for the RCPAQAP and participation rates (maximum of 87% per survey; average 68% for stained slides and 66% for questionnaires) were commendable, particularly considering these were optional undertakings with some exercises not applicable to all laboratories. The great majority of submitted slides were scored as satisfactory, and there was an especially high standard for the immunocytochemical staining exercise with 95% considered satisfactory, including 50.6% with a perfect score. Reasons for suboptimal scores were provided for potential quality improvement for interested laboratories. A wealth of information relating to laboratory practice was provided to the RCPAQAP which was collated and summarised for laboratory use. CONCLUSIONS: The provision of a technical module in cytopathology is both a feasible and valuable undertaking of interest to laboratories which should become standard practice for cytopathology external quality assurance providers. PMID- 27678253 TI - Similar below-ground carbon cycling dynamics but contrasting modes of nitrogen cycling between arbuscular mycorrhizal and ectomycorrhizal forests. AB - Compared with ectomycorrhizal (ECM) forests, arbuscular mycorrhizal (AM) forests are hypothesized to have higher carbon (C) cycling rates and a more open nitrogen (N) cycle. To test this hypothesis, we synthesized 645 observations, including 22 variables related to below-ground C and N dynamics from 100 sites, where AM and ECM forests co-occurred at the same site. Leaf litter quality was lower in ECM than in AM trees, leading to greater forest floor C stocks in ECM forests. By contrast, AM forests had significantly higher mineral soil C concentrations, and this result was strongly mediated by plant traits and climate. No significant differences were found between AM and ECM forests in C fluxes and labile C concentrations. Furthermore, inorganic N concentrations, net N mineralization and nitrification rates were all higher in AM than in ECM forests, indicating 'mineral' N economy in AM but 'organic' N economy in ECM trees. AM and ECM forests show systematic differences in mineral vs organic N cycling, and thus mycorrhizal type may be useful in predicting how different tree species respond to multiple environmental change factors. By contrast, mycorrhizal type alone cannot reliably predict below-ground C dynamics without considering plant traits and climate. PMID- 27678254 TI - Mendeley Mobile: Powerful Cloud-Based Article and Reference Management in Your Pocket. PMID- 27678250 TI - Time-resolved infrared spectroscopy in the study of photosynthetic systems. AB - Time-resolved (TR) infrared (IR) spectroscopy in the nanosecond to second timescale has been extensively used, in the last 30 years, in the study of photosynthetic systems. Interesting results have also been obtained at lower time resolution (minutes or even hours). In this review, we first describe the used techniques-dispersive IR, laser diode IR, rapid-scan Fourier transform (FT)IR, step-scan FTIR-underlying the advantages and disadvantages of each of them. Then, the main TR-IR results obtained so far in the investigation of photosynthetic reactions (in reaction centers, in light-harvesting systems, but also in entire membranes or even in living organisms) are presented. Finally, after the general conclusions, the perspectives in the field of TR-IR applied to photosynthesis are described. PMID- 27678256 TI - Homogenization of a Directed Dispersal Model for Animal Movement in a Heterogeneous Environment. AB - The dispersal patterns of animals moving through heterogeneous environments have important ecological and epidemiological consequences. In this work, we apply the method of homogenization to analyze an advection-diffusion (AD) model of directed movement in a one-dimensional environment in which the scale of the heterogeneity is small relative to the spatial scale of interest. We show that the large (slow) scale behavior is described by a constant-coefficient diffusion equation under certain assumptions about the fast-scale advection velocity, and we determine a formula for the slow-scale diffusion coefficient in terms of the fast-scale parameters. We extend the homogenization result to predict invasion speeds for an advection-diffusion-reaction (ADR) model with directed dispersal. For periodic environments, the homogenization approximation of the solution of the AD model compares favorably with numerical simulations. Invasion speed approximations for the ADR model also compare favorably with numerical simulations when the spatial period is sufficiently small. PMID- 27678257 TI - Giant Hollow Heterometallic Polyoxoniobates with Sodalite-Type Lanthanide Tungsten-Oxide Cages: Discrete Nanoclusters and Extended Frameworks. AB - The first series of niobium-tungsten-lanthanide (Nb-W-Ln) heterometallic polyoxometalates {Ln12 W12 O36 (H2 O)24 (Nb6 O19 )12 } (Ln=Y, La, Sm, Eu, Yb) have been obtained, which are comprised of giant cluster-in-cluster-like ({Ln12 W12 }-in-{Nb72 }) structures built from 12 hexaniobate {Nb6 O19 } clusters gathered together by a rare 24-nuclearity sodalite-type heterometal-oxide cage {Ln12 W12 O36 (H2 O)24 }. The Nb-W-Ln clusters present the largest multi-metal polyoxoniobates and a series of rare high-nuclearity 4d-5d-4f multicomponent clusters. Furthermore, the giant Nb-W-Ln clusters may be isolated as discrete inorganic alkali salts and can be used as building blocks to form high dimensional inorganic-organic hybrid frameworks. PMID- 27678255 TI - Content-Based Image Retrieval System for Pulmonary Nodules: Assisting Radiologists in Self-Learning and Diagnosis of Lung Cancer. AB - Visual information of similar nodules could assist the budding radiologists in self-learning. This paper presents a content-based image retrieval (CBIR) system for pulmonary nodules, observed in lung CT images. The reported CBIR systems of pulmonary nodules cannot be put into practice as radiologists need to draw the boundary of nodules during query formation and feature database creation. In the proposed retrieval system, the pulmonary nodules are segmented using a semi automated technique, which requires a seed point on the nodule from the end-user. The involvement of radiologists in feature database creation is also reduced, as only a seed point is expected from radiologists instead of manual delineation of the boundary of the nodules. The performance of the retrieval system depends on the accuracy of the segmentation technique. Several 3D features are explored to improve the performance of the proposed retrieval system. A set of relevant shape and texture features are considered for efficient representation of the nodules in the feature space. The proposed CBIR system is evaluated for three configurations such as configuration-1 (composite rank of malignancy "1","2" as benign and "4","5" as malignant), configuration-2 (composite rank of malignancy "1","2", "3" as benign and "4","5" as malignant), and configuration-3 (composite rank of malignancy "1","2" as benign and "3","4","5" as malignant). Considering top 5 retrieved nodules and Euclidean distance metric, the precision achieved by the proposed method for configuration-1, configuration-2, and configuration-3 are 82.14, 75.91, and 74.27 %, respectively. The performance of the proposed CBIR system is close to the most recent technique, which is dependent on radiologists for manual segmentation of nodules. A computer-aided diagnosis (CAD) system is also developed based on CBIR paradigm. Performance of the proposed CBIR-based CAD system is close to performance of the CAD system using support vector machine. PMID- 27678258 TI - Genetic correlations between dressage, show jumping and studbook-entry inspection traits in a process of specialization in Dutch Warmblood horses. AB - Sport performance in dressage and show jumping are two important traits in the breeding goals of many studbooks. To determine the optimum selection scheme for jumping and dressage, knowledge is needed on the genetic correlation between both disciplines and between traits measured early in life and performance in competition in each discipline. This study aimed to estimate genetic parameters to support decision-making on specialization of breeding horses for dressage and show jumping in Dutch warmblood horses. Genetic correlations between performance of horses in dressage and show jumping were estimated as well as the genetic correlation between traits recorded during studbook-entry inspections and performance in dressage and show jumping competitions. The information on competition comprised the performance of 82 694 horses in dressage and 62 072 horses in show jumping, recorded in the period 1993-2012. For 26 056 horses, information was available for both disciplines. The information on traits recorded at studbook-entry inspections comprised 62 628 horses, recorded in the period 1992-2013. Genetic parameters were estimated from the whole dataset and from a subset without horses recorded in both disciplines. Additionally, the genetic parameters were estimated in three different time periods defined by horses' birth year. The genetic correlation between dressage and show jumping in the whole dataset was -0.23, and it was -0.03 when it was estimated from horses recorded in only one discipline. The genetic correlation between dressage and show jumping was more negative in the most recent time period in all the cases. The more negative correlation between disciplines in more recent time periods was not reflected in changes in the correlations between competitions traits and the traits recorded in the studbook-first inspection. These results suggest that a breeding programme under specialization might be most effective defining two separate aggregate breeding goals for each of the disciplines. PMID- 27678259 TI - Copper Complexes of New Redox-Active 4,5-Bisguanidino-Substituted Benzodioxole Ligands: Control of the Electronic Structure by Counter-Ligands, Solvent, and Temperature. AB - Herein, we analyze the possibility of controlling the electronic structure of mononuclear copper complexes featuring new redox-active 4,5-bisguanidino substituted benzodioxole ligands. The nature of the guanidino groups, the anionic counter-ligands, the applied solvent (polarity), and the temperature are the parameters that decide if a CuII complex with neutral ligand unit or a CuI complex with radical monocationic ligand unit is the adequate description. Under special conditions, a temperature-dependent equilibrium of the two valence tautomeric forms (CuII /neutral ligand and CuI /radical monocationic ligand) is achieved. Removal of a ligand-centered electron from a paramagnetic CuII complex with a neutral ligand unit leads to a diamagnetic CuI complex with a dicationic ligand unit through a redox-induced electron-transfer (RIET) process. PMID- 27678260 TI - Invasive and Non-invasive Electrical Pericranial Nerve Stimulation for the Treatment of Chronic Primary Headaches. AB - Chronic primary headaches are widespread disorders which cause significant quality of life and socioprofessional impairment. Available pharmacological treatments have often a limited efficacy and/or can generate unbearable side effects. Electrical nerve stimulation is a well-known non-destructive method of pain modulation which has been recently applied to headache management. In this review, we summarise recent advances in invasive and non-invasive neurostimulation techniques targeting pericranial structures for the treatment of chronic primary headaches, chiefly migraine and cluster headache: occipital nerve, supraorbital nerve, vagus nerve, and sphenopalatine ganglion stimulations. Invasive neurostimulation therapies have offered a new hope to drug-refractory headache sufferers but are not riskless and should be proposed only to chronic patients who failed to respond to most existing preventives. Non-invasive neurostimulation devices are user-friendly, safe and well tolerated and are thus taking an increasing place in the multidisciplinary therapeutical armamentarium of primary headaches. PMID- 27678261 TI - Amelioration of X-Linked Related Autophagy Failure in Danon Disease With DNA Methylation Inhibitor. AB - BACKGROUND: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a deficiency in lysosome-associated membrane protein-2 (LAMP2). In female patients, a later onset and less severe clinical phenotype have been attributed to the random inactivation of the X chromosome carrying the mutant diseased allele. We generated a patient-specific induced pluripotent stem cell (iPSCs)-based model of Danon disease to evaluate the therapeutic potential of Xi-chromosome reactivation using a DNA methylation inhibitor. METHODS: Using whole-exome sequencing, we identified a nonsense mutation (c.520C>T, exon 4) of the LAMP2 gene in a family with Danon disease. We generated iPSC lines from somatic cells derived from the affected mother and her 2 sons, and we then differentiated them into cardiomyocytes (iPSC-CMs) for modeling the histological and functional signatures, including autophagy failure of Danon disease. RESULTS: Our iPSC-CM platform provides evidence that random inactivation of the wild-type and mutant LAMP2 alleles on the X chromosome is responsible for the unusual phenotype in female patients with Danon disease. In vitro, iPSC-CMs from these patients reproduced the histological features and autophagy failure of Danon disease. Administration of the DNA demethylating agent 5-aza-2'-deoxycytidine reactivated the silent LAMP2 allele in iPSCs and iPSC-CMs in female patients with Danon disease and ameliorated their autophagy failure, supporting the application of a patient-specific iPSC platform for disease modeling and drug screening. CONCLUSIONS: Our iPSC-CM platform provides novel mechanistic and therapeutic insights into the contribution of random X chromosome inactivation to disease phenotype in X-linked Danon disease. PMID- 27678262 TI - Genetic and Pharmacologic Inhibition of the Chemokine Receptor CXCR2 Prevents Experimental Hypertension and Vascular Dysfunction. AB - BACKGROUND: The recruitment of leukocytes to the vascular wall is a key step in hypertension development. Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in hypertension development and the underlying mechanisms remain unknown. METHODS: Angiotensin II (490 ng.kg-1.min-1) or deoxycorticosterone acetate (DOCA) salt-induced mouse hypertensive models in genetic ablation, pharmacologic inhibition of CXCR2, and adoptive bone marrow transfer mice were used to determine the role of CXCR2 in hypertension (measured by radiotelemetry and tail-cuff system), inflammation (verified by flow cytometry and quantitative real-time polymerase chain reaction [PCR] analysis), vascular remodeling (studied by haematoxylin and eosin and Masson's trichrome staining), vascular dysfunction (assessed by aortic ring), and oxidative stress (indicated by nicotinamide adenine dinucleotide phosphate [NADPH] oxidase activity, dihydroethidium staining, and quantitative real-time PCR analysis). Moreover, the blood CXCR2+ cells in normotensive controls and hypertension patients were analyzed by flow cytometry. RESULTS: Angiotensin II significantly upregulated the expression of CXCR2 mRNA and protein and increased the number of CD45+ CXCR2+ cells in mouse aorta (n=8 per group). Selective CXCR2 knockout (CXCR2-/-) or pharmacological inhibition of CXCR2 markedly reduced angiotensin II- or DOCA-salt-induced blood pressure elevation, aortic thickness and collagen deposition, accumulation of proinflammatory cells into the vascular wall, and expression of cytokines (n=8 per group). CXCR2 inhibition also ameliorated angiotensin II-induced vascular dysfunction and reduced vascular superoxide formation, NADPH activity, and expression of NADPH oxidase subunits (n=6 per group). Bone marrow reconstitution of wild-type mice with CXCR2-/- bone marrow cells also significantly abolished angiotensin II-induced responses (n=6 per group). It is important to note that CXCR2 blockade reversed established hypertension induced by angiotensin II or DOCA-salt challenge (n=10 per group). Furthermore, we demonstrated that CXCR2+ proinflammatory cells were higher in hypertensive patients (n=30) compared with normotensive individuals (n=20). CONCLUSIONS: Infiltration of CXCR2+ cells plays a pathogenic role in arterial hypertension and vascular dysfunction. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat hypertension. PMID- 27678263 TI - Is Hypertension a Bone Marrow Disease? PMID- 27678264 TI - Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study. AB - BACKGROUND: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia. METHODS: In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean+/ standard deviation] 59.7+/-8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin % hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease. RESULTS: Retinal arteriolar % dilation was (mean+/-standard deviation) 3.4+/-2.8 in normal glucose metabolism, 3.0+/-2.7 in prediabetes, and 2.3+/-2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean+/-standard deviation) 1235+/-810 in normal glucose metabolism, 1109+/-748 in prediabetes, and 937+/-683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 [-163 to 72]) with further deterioration in T2DM (B=-184 [-297 to -71]) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 [-0.15 to -0.05], P<0.001 and standardized B=-0.13 [-0.19 to -0.07], P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 [-0.15 to -0.04], P<0.001 and standardized B=-0.10 [-0.15 to -0.04], P=0.002, respectively). CONCLUSION: Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure. PMID- 27678265 TI - Promoting Cardiomyogenesis of hBMSC with a Forming Self-Assembly hBMSC Microtissues/HA-GRGD/SF-PCL Cardiac Patch Is Mediated by the Synergistic Functions of HA-GRGD. AB - Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(epsilon-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces. The results show that the proliferations of hBMSC on HGSP patches significantly exceed those on the other patches, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) 2-(4-sulfophenyl)-2H-tetrazolium assay. Notably, the formation of 5-aza inducing cardiomyogenic differentiations of hBMSCMT/HGSP patches is observed with typical sizes of ~317 MUm wide and 26 MUm high. The cardiomyogenesis of hBMSCMT/HGSP patches including the expressions of cardiac-specific genes (e.g., Gata4) and proteins (e.g., connexin43 (CX43)) significantly exceeds those of hBMSC monolayer on the HSP and SP patches. Promoting in vitro cardiomyogenesis of hBMSC with forming cardiomyogenic differentiation of hBMSCMT/HGSP hybrid patch is possibly mediated by the synergistic functions of HA-GRGD on enhancing the activity of F actin. The hBMSCMT/HGSP cardiac patch may be further employed to cardiac tissue engineering. PMID- 27678266 TI - Predictive medicine: towards a multi-parametric imaging for a personal risk stratification. PMID- 27678268 TI - A kinetic chain growth algorithm in coarse-grained simulations. AB - We propose a kinetic chain growth algorithm for coarse-grained (CG) simulations in this work. By defining the reaction probability, it delivers a description of consecutive polymerization process. This algorithm is validated by modeling the process of individual styrene monomers polymerizing into polystyrene chains, which is proved to correctly reproduce the properties of polymers in experiments. By bridging the relationship between the generic chain growth process in CG simulations and the chemical details, the impediment to reaction can be reflected. Regarding to the kinetics, it models a polymerization process with an Arrhenius-type reaction rate coefficient. Moreover, this algorithm can model both the gradual and jump processes of the bond formation, thus it readily encompasses several kinds of previous CG models of chain growth. With conducting smooth simulations, this algorithm can be potentially applied to describe the variable macroscopic features of polymers with the process of polymerization. The algorithm details and techniques are introduced in this article. (c) 2016 Wiley Periodicals, Inc. PMID- 27678267 TI - High clinical and morphologic response using 90Y-DOTA-octreotate sequenced with 177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours. AB - PURPOSE: Bulky disease is an adverse prognostic factor for 177Lu-DOTA-octreotate (177Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). 90Y-DOTA octreotate (90Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than 177Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. METHODS: We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of 90Y DOTATATE followed by 2-3 cycles of 177Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression free and overall survival. RESULTS: Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq 90Y-DOTATATE, and 21 GBq 177Lu DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. CONCLUSION: PRCRT with 90Y DOTATATE followed by 177Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved treatments, particularly given the adverse prognostic features of this cohort. PMID- 27678270 TI - Titanium-Promoted Cross-Coupling for the Selective Synthesis of Polysubstituted, Conjugated Amides. AB - alpha,beta-Unsaturated amides are important building blocks and are key structural elements in a number of biologically active natural products. Despite their importance and prevalence, few methods exist to prepare conjugated amides directly and modularly. To address this gap, a titanium-promoted coupling of alkynes and isocyanates has been developed. The method is highly stereoselective, producing only the E isomer with good chemoselectivity and regioselectivity (>95/5), for unsymmetrical internal alkynes that contain a steric bias. The reactive titanacyclopentene intermediate formed from the coupling of the alkyne and isocyanate was additionally reacted with various electrophiles to access tetrasubstituted enamides. PMID- 27678269 TI - Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL. AB - The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services. PMID- 27678271 TI - Can intraperitoneal bupivacaine decreases pain in patients undergoing laparoscopic live donor nephrectomy? A randomized control trial. AB - PURPOSE: To evaluate effect of intraperitoneal bupivacaine on postoperative pain in patients undergoing laparoscopic live donor nephrectomy. METHODS: Hundred patients undergoing laparoscopic live donor nephrectomy were included in the study and were divided randomly into two groups based on computer-generated randomization chart of fifty each. Patients were made familiar with VAS chart preoperatively. Group A received 20 mL of 0.5 % bupivacaine, while group B patients received 20 mL of 0.9 % normal saline intraperitoneally Postoperatively, patients were assessed based on VAS and requirement of rescue analgesic, hemodynamic parameters and presence of any adverse effects. Student's t test was used for statistical analysis. RESULTS: At all-time interval, mean pain scores were higher in group B than group A. The difference between the mean pain scores was statistically significant (p < 0.05) at 0, 2 and 4 h. The mean dose of rescue analgesia (pentazocin, 30 mg in one vial) in group A was 33 +/- 26 mg which was significantly less as compared to group B where it was 62 +/- 28 mg. There was statistically insignificant difference between all cardiorespiratory factories at all-time intervals except for heart rate and mean blood pressure at 0 h in group A as compared to group B. CONCLUSIONS: Intraperitoneal bupivacaine is a simple, safe, inexpensive method for control of postoperative pain in patients undergoing laparoscopic live donor nephrectomy. Use of the correct dose and concentration of the drug are essential for effective pain control. PMID- 27678273 TI - Current status of proteomics of esophageal carcinoma. AB - INTRODUCTION: Esophageal cancer (EC) is one of the most common causes of cancer related death worldwide. Identifying suitable biomarkers for early diagnosis as well as predicting lymph node metastasis, prognosis and the therapeutic response of EC is essential for the effective and efficient management for EC. There is an urgent need to develop effective, novel approaches for patients who do not respond to conventional treatment. Areas covered: EC is characterized by the presence of two main histological types such as squamous cell carcinoma and adenocarcinoma, which differ in their response to treatments and prognosis. Thus, this review describes the latest research into biomarkers and novel treatment targets generated by cancer proteomics for the two main histological types. Finally, the main difficulties facing the translation of biomarkers and novel treatment targets into the clinical settings are discussed. Expert commentary: EC proteomics have provided useful results and, after their validation, novel clinical tools should be developed to improve the clinical outcomes for EC patients. PMID- 27678272 TI - High-dose chemotherapy as salvage treatment in germ-cell cancer: when, in whom and how. AB - Over the past two decades, the use of well-validated, guideline-based strategies resulted in high cure rates in patients with germ-cell cancer (GCC) often despite widespread metastatic disease at initial presentation. Yet, about 30 % of patients diagnosed with metastatic disease corresponding to about 5-10 % of GCC patients overall will experience disease progression or recurrence at some time point of their disease with the need for salvage treatment. Salvage treatment is more complex and less well validated than first-line treatment: Its rare patient cohorts are more heterogeneous and prognostic factors impact more compared to other treatment scenarios. In patients with metastatic GCC, there are several scenarios in which first-line treatment strategies can fail (Fig. 1). Prior to initiation of any salvage treatment, several considerations have to be made, which will be addressed in this review: verification that first-line treatment has indeed failed, estimation of the adequacy and the effectiveness of first-line treatment, search for metastatic sites and extent of disease recurrence, assessment of known prognostic factors and finally the choice of the optimal salvage strategy taking into account the aforementioned variables. High-dose chemotherapy will be a rational choice for many patients in need of salvage treatment, but careful patient selection will be required to avoid overtreatment and unnecessary long-term toxicity. PMID- 27678274 TI - Impaired memory for material related to a problem solved prior to encoding: suppression at learning or interference at recall? AB - Earlier research by the author revealed that material encoded incidentally in a speeded affective classification task and related to the demands of a divergent problem tends to be recalled worse in participants who solved the problem prior to encoding than in participants in the control, no-problem condition. The aim of the present experiment was to replicate this effect with a new, size-comparison orienting task, and to test for possible mechanisms of impaired recall. Participants either solved a problem before the orienting task or not, and classified each item in this task either once or three times. There was a reliable effect of impaired recall of problem-related items in the repetition condition, but not in the no-repetition condition. Solving the problem did not influence repetition priming for these items. These results support an account that attributes the impaired recall to inhibitory processes at learning and speak against a proactive interference explanation. However, they can be also accommodated by an account that refers to inefficient context cues and competitor interference at retrieval. PMID- 27678276 TI - [Not Available]. PMID- 27678275 TI - [Not Available]. PMID- 27678277 TI - [Not Available]. PMID- 27678278 TI - Pelvic inflammatory disease and salpingitis: incidence of primary and repeat episodes in England. AB - Pelvic inflammatory disease (PID) and more specifically salpingitis (visually confirmed inflammation) is the primary cause of tubal factor infertility and is an important risk factor for ectopic pregnancy. The risk of these outcomes increases following repeated episodes of PID. We developed a homogenous discrete time Markov model for the distribution of PID history in the UK. We used a Bayesian framework to fully propagate parameter uncertainty into the model outputs. We estimated the model parameters from routine data, prospective studies, and other sources. We estimated that for women aged 35-44 years, 33.6% and 16.1% have experienced at least one episode of PID and salpingitis, respectively (diagnosed or not) and 10.7% have experienced one salpingitis and no further PID episodes, 3.7% one salpingitis and one further PID episode, and 1.7% one salpingitis and ?2 further PID episodes. Results are consistent with numerous external data sources, but not all. Studies of the proportion of PID that is diagnosed, and the proportion of PIDs that are salpingitis together with the severity distribution in different diagnostic settings and of overlap between routine data sources of PID would be valuable. PMID- 27678279 TI - Twelve tips for assessing surgical performance and use of technical assessment scales. AB - Using validated assessment scales for technical competence can help structure and standardize assessment and feedback for both the trainee and the supervisor and thereby avoid bias and drive learning. Correct assessment of operative skills can establish learning curves and allow adequate monitoring. However, the assessment of surgical performance is not an easy task, since it includes many proxy parameters, which are hard to measure. Although numerous technical assessment scales exist, both within laparoscopic and open surgery, the validity evidence is often sparse, and this can raise doubts about reliability and educational outcome. Furthermore, the implementation of technical assessment scales varies due to several obstacles and doubts about accurate use. In this 12-tips article, we aim to give the readers a critical and useful appraisal of some of the common questions and misunderstandings regarding the use of surgical assessment scales and provide tips to ease and overcome potential pitfalls. PMID- 27678280 TI - Introduction of revised "Aims and Scope" for Clinical & Experimental Metastasis. PMID- 27678281 TI - Ligand-based and e-pharmacophore modeling, 3D-QSAR and hierarchical virtual screening to identify dual inhibitors of spleen tyrosine kinase (Syk) and janus kinase 3 (JAK3). AB - The clinical efficacy of multiple kinase inhibitors has caught the interest of Pharmaceutical and Biotech researchers to develop potential drugs with multi kinase inhibitory activity for complex diseases. In the present work, we attempted to identify dual inhibitors of spleen tyrosine kinase (Syk) and janus kinase 3 (JAK3), keys players in immune signaling, by developing ideal pharmacophores integrating Ligand-based pharmacophore models (LBPMs) and Structure-based pharmacophore models (SBPMs), thereby projecting the optimum pharmacophoric required for inhibition of both the kinases. The four point LBPM; ADPR.14 suggested the presence of one hydrogen bond acceptor, one hydrogen bond donor, one positive ionizable, and one ring aromatic feature for Syk inhibitory activity and AADH.54 proposed the necessity of two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature for JAK3 inhibitory activity. To our interest, SBPMs identified additional ring aromatic features required for inhibition of both the kinases. For Syk inhibitory activity, the hydrogen bond acceptor feature indicated by LBPM was devoid of forming hydrogen bonding interaction with the hinge region amino acid residue (Ala451). Thus merging the information revealed by both LBPMs and SBPMs, ideal pharmacophore models i.e. ADPRR.14 (Syk) and AADHR.54 (JAK3) were generated. These models after rigorous statistical validation were used for screening of Asinex database. The systematic virtual screening protocol, including pharmacophore and docking-based screening, ADME property, and MM-GBSA energy calculations, retrieved final 10 hits as dual inhibitors of Syk and JAK3. Final 10 hits thus obtained can aid in the development of potential therapeutic agents for autoimmune disorders. Also the top two hits were evaluated against both the enzymes. PMID- 27678283 TI - Risk of hemorrhage in abnormally invasive placenta according to its management. AB - Severe hemorrhage is a major concern during operative procedures for abnormally invasive placenta (AIP). We reviewed published literature with the objective to provide evidence of blood loss with the most common treatment options for AIP. We selected 54 articles that fulfilled the inclusion criteria. Cesarean hysterectomy, with or without occlusion balloons in the internal iliac arteries, was the treatment associated with the greatest blood loss. Major blood loss was also associated with the placenta left in situ (reported in 3 of 10 articles), and with uterine artery embolization (reported in 3 of 15 articles). The best outcomes were seen for cesarean hysterectomy with balloon occlusion of the common iliac arteries (CIA; 9 patients, including 1 with major blood loss), balloon occlusion of the abdominal aorta (27 patients, no major blood loss) and conservative surgery (99 patients, including one with major blood loss). In conclusion, cesarean hysterectomy with balloon occlusion of the CIA or abdominal aorta, and conservative treatments seem to have the best outcomes. However, our results are based on a small number of articles. Hence, it is necessary to have available more reports on the outcomes of these treatments, to arrive at a more definitive conclusion. PMID- 27678282 TI - Is it necessary to investigate rapamycin-modulated autophagy during the development of experimental osteoporosis in female rat? PMID- 27678284 TI - Drug metabolism by flavin-containing monooxygenases of human and mouse. AB - INTRODUCTION: Flavin-containing monooxygenases (FMOs) play an important role in drug metabolism. Areas covered: We focus on the role of FMOs in the metabolism of drugs in human and mouse. We describe FMO genes and proteins of human and mouse; the catalytic mechanism of FMOs and their significance for drug metabolism; differences between FMOs and CYPs; factors contributing to potential underestimation of the contribution of FMOs to drug metabolism; the developmental and tissue-specific expression of FMO genes and differences between human and mouse; and factors that induce or inhibit FMOs. We discuss the contribution of FMOs of human and mouse to the metabolism of drugs and how genetic variation of FMOs affects drug metabolism. Finally, we discuss the utility of animal models for FMO-mediated drug metabolism in humans. Expert opinion: The contribution of FMOs to drug metabolism may be underestimated. As FMOs are not readily induced or inhibited and their reactions are generally detoxifications, the design of drugs that are metabolized predominantly by FMOs offers clinical advantages. Fmo1(-/ ),Fmo2(-/-),Fmo4(-/-) mice provide a good animal model for FMO-mediated drug metabolism in humans. Identification of roles for FMO1 and FMO5 in endogenous metabolism has implications for drug therapy and initiates an exciting area of research. PMID- 27678285 TI - Antimicrobial resistance in Shiga toxin-producing Escherichia coli serogroups O157 and O26 isolated from human cases of diarrhoeal disease in England, 2015. AB - OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) are zoonotic and transmission to humans occurs via contaminated food or contact with infected animals. In this study, WGS data were used to predict antimicrobial resistance (AMR) in STEC from symptomatic human cases to assess the extent of transmission of antibiotic-resistant E. coli from animals to humans. METHODS: WGS data from 430 isolates of STEC were mapped to genes known to be associated with phenotypic AMR. Susceptibility testing was performed by a breakpoint method on all viable isolates exhibiting resistance to at least one antimicrobial. RESULTS: 327/396 (82.6%) of STEC O157 and 22/34 (64.7%) of STEC O26 lacked identifiable resistance genes and were predicted to be fully susceptible to 11 diverse classes of antimicrobials. For the remaining 81 isolates, 74 were phenotypically tested and there was concordance between WGS-predicted resistance and expression of phenotypic resistance. The most common resistance profile was ampicillin, streptomycin, trimethoprim/sulphonamide and tetracycline occurring in 25 (5.8%) isolates. Resistance to other antimicrobials, including resistance to chloramphenicol (2.1%), resistance to azithromycin (0.2%) and reduced susceptibility to ciprofloxacin (2.6%), was less frequent. Three isolates were identified as ESBL producers. CONCLUSIONS: beta-Lactams, trimethoprim/sulphonamides and tetracyclines account for the majority of therapeutic antimicrobials sold for veterinary use and this may be a risk factor for the presence of AMR in domestically acquired human clinical isolates of STEC. Isolates that were resistant to ampicillin, streptomycin, sulphonamide, tetracycline and azithromycin and had reduced susceptibility to ciprofloxacin were associated with cases who reported recent travel abroad. PMID- 27678286 TI - Evaluation of empirical treatment for blood culture-negative endocarditis. AB - OBJECTIVES: Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality. PATIENTS AND METHODS: We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B. RESULTS: We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocol's failure, such as poorly tolerated surgery. CONCLUSIONS: Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time. PMID- 27678287 TI - Preserved and attenuated electrophysiological correlates of visual spatial attention in elderly subjects. AB - Healthy aging is associated with changes in many neurocognitive functions. While on the behavioral level, visual spatial attention capacities are relatively stable with increasing age, the underlying neural processes change. In this study, we investigated attention-related modulations of the stimulus-locked event related potential (ERP) and occipital oscillations in the alpha band (8-14Hz) in young and elderly participants. Both groups performed a visual attention task equally well and the ERP showed comparable attention-related modulations in both age groups. However, in elderly subjects, oscillations in the alpha band were massively reduced both during the task and in the resting state and the typical task-related lateralized pattern of alpha activity was not observed. These differences between young and elderly participants were observed on the group level as well as on the single trial level. The results indicate that younger and older adults use different neural strategies to reach the same performance in a covert visual spatial attention task. PMID- 27678288 TI - Expression and purification of mouse Ttyh1 fragments as antigens to generate Ttyh1-specific monoclonal antibodies. AB - Ttyh1 is a murine homolog of the Drosophila Tweety and is predicted as a five pass transmembrane protein. The Ttyh1 mRNA is expressed in mouse brain tissues with a restricted pattern and in human glioma cells. Ttyh1 protein may function as a large-conductance chloride channel, however, the role of Ttyh1 in normal neural development and tumorigenesis has been largely unknown, at least partially due to the lack of effective antibodies. Here we report the expression in E. coli and purification of two recombinant Ttyh1 protein fragments corresponding to one of the predicted extracellular domains and the carboxyl terminus of the mouse Ttyh1. With these Ttyh1 protein products, a set of monoclonal antibodies (mAbs) against the mouse Ttyh1 protein was established by using conventional hybridoma techniques. The specificity of the anti-Ttyh1 mAbs was determined based on their activities in Western blotting and immunofluorescent analysis using embryonic brain tissues and cultured mouse neural stem cells (NSCs). We also show that the mouse Ttyh1 protein was expressed in cultured NSCs, most likely in membrane and cytoplasm. In mouse embryonic brains, it appeared that the Ttyh1 protein was specifically expressed in the apical edge of the ventricular zone as puncta-like structures, as determined by using immunofluorescence. Taken together, our study provided a useful tool for further exploration of the biological functions and pathological significance of Ttyh1 in mice. PMID- 27678289 TI - The Relationship Between Cognitive Functioning and the JNC-8 Guidelines for Hypertension in Older Adults. AB - BACKGROUND: Guidelines for hypertension treatment by the Eighth Joint National Committee (JNC-8) in 2014 recommended a target systolic blood pressure (BP) of <150/<90 mmHg in persons older than 60 years, in contrast to the 2003 JNC-7 recommendations of systolic BP <140 mmHg. This study evaluated the implications of raising the BP target on cognitive functioning and conversion from normal cognition to mild cognitive impairment (MCI). METHODS: This was a longitudinal study of individuals older than 60 years enrolled in the NIH-NIA Alzheimer's Disease Centers. All had normal cognition at baseline. 453 participants were taking BP medications and had readings of <140/<90 mmHg at four annual visits (reference group). Two other groups consisted of participants with either systolic BP of 140-149 mmHg (n = 112) or >=150 mmHg (n = 280) on three or four annual visits. RESULTS: Compared with the reference and the 140-149 mmHg groups, those with BP >=150 mmHg exhibited poorer cognitive status by Year 4 on the Mini Mental State Exam, and they had a higher risk of conversion to MCI. The 140-149 mmHg exhibited poorer performance than the reference group on domains assessing attention and executive functioning. In contrast, their performance was not significantly different from those with BP >=150 mmHg. CONCLUSIONS: Persons with BP >=150 mmHg show a faster global cognitive decline and transition to MCI than those with lower BP readings. However, the poor cognitive performance in the attention and executive functioning domains for the 140-149 mmHg group indicates the need for further research evaluating the newer recommended cutoff. PMID- 27678291 TI - Caffeine Intake and Dementia Risk-A Health Benefit From One of Life's Simple Pleasures? PMID- 27678290 TI - Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women's Health Initiative Memory Study. AB - BACKGROUND: Nonhuman studies suggest a protective effect of caffeine on cognition. Although human literature remains less consistent, reviews suggest a possible favorable relationship between caffeine consumption and cognitive impairment or dementia. We investigated the relationship between caffeine intake and incidence of cognitive impairment or probable dementia in women aged 65 and older from the Women's Health Initiative Memory Study. METHODS: All women with self-reported caffeine consumption at enrollment were included (N = 6,467). In 10 years or less of follow-up with annual assessments of cognitive function, 388 of these women received a diagnosis of probable dementia based on a 4-phase protocol that included central adjudication. We used proportional hazards regression to assess differences in the distributions of times until incidence of probable dementia or composite cognitive impairment among women grouped by baseline level of caffeine intake, adjusting for risk factors (hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption). RESULTS: Women consuming above median levels (mean intake = 261mg) of caffeine intake for this group were less likely to develop incident dementia (hazard ratio = 0.74, 95% confidence interval [0.56, 0.99], p = .04) or any cognitive impairment (hazard ratio = 0.74, confidence interval [0.60, 0.91], p = .005) compared to those consuming below median amounts (mean intake = 64mg) of caffeine for this group. CONCLUSION: Our findings suggest lower odds of probable dementia or cognitive impairment in older women whose caffeine consumption was above median for this group and are consistent with the existing literature showing an inverse association between caffeine intake and age-related cognitive impairment. PMID- 27678293 TI - The expression of glial cell line-derived neurotrophic factor mRNA by antidepressants involves matrix metalloproteinase-9 activation in rat astroglial cells. AB - Neurotrophic/growth factors derived from glial cells, especially astrocytes, have been implicated in mood disorders and the pharmacological effects of antidepressant drugs. Previous studies demonstrated that the release of glial cell line-derived neurotrophic factor (GDNF) induced by the tricyclic antidepressant amitriptyline was significantly inhibited by a broad-spectrum matrix metalloproteinase (MMP) inhibitor in rat C6 astroglial cells (C6 cells). However, it is unknown whether amitriptyline affects MMP enzymatic activity or expression, and the MMP subtype has yet to be identified. The current study measured the effect of antidepressants on MMP activity with gelatin zymography, an in vitro assay for enzymatic activity, in C6 cells and primary cultured rat astrocytes (primary astrocytes). Treatment with amitriptyline increased zymographic MMP-9 activity without changing MMP-9 mRNA expression in C6 cells. Several different classes of antidepressants significantly increased zymographic MMP-9 activity in C6 cells and primary astrocytes, whereas antipsychotic drugs without antidepressant pharmacological activity did not. The amitriptyline induced expression of GDNF mRNA was completely blocked by selective inhibition of MMP-9 in C6 cells. Treatment of C6 cells and primary astrocytes with exogenous recombinant MMP-9 increased GDNF mRNA expression, similar to that observed with amitriptyline. Inhibiting MMP-3 blocked amitriptyline-induced zymographic MMP-9 activation in C6 cells and primary astrocytes, indicating that MMP-3 is necessary for MMP-9 activity. The current study suggests that MMP-9 activation is indispensable in the amitriptyline-induced expression of GDNF mRNA in astrocytes and further supports a role of astrocytic neurotrophic/growth factors in the pharmacological effect of antidepressants. PMID- 27678292 TI - Tungsten: an Emerging Toxicant, Alone or in Combination. AB - PURPOSE OF REVIEW: Tungsten is an emerging environmental toxicant, yet our understanding of the potential risks of exposure on human health is still limited. RECENT FINDINGS: In this review, we will discuss populations most at risk of exposure to high concentrations of tungsten. In addition, we will highlight what is known about the toxicity profile of tungsten compounds, based on epidemiological, in vitro, and in vivo studies, focusing on bone, immune, pulmonary, and cancer outcomes. Of note, emerging evidence indicates that tungsten can augment the effects of other stimulants, stressors, and toxicants. Of particular importance may be tungsten-cobalt mixtures that seem to be more toxic than either metal alone. This is important because it means that we cannot just evaluate the toxicity of tungsten in isolation. Finally, we still have limited information of how many of the in vitro and in vivo findings translate to human populations, so it will be important to conduct epidemiology studies in highly exposed populations to adequately address the potential risks of tungsten exposure on human health. Together, we discuss recent findings that support further investigation into the toxicities of tungsten alone and in combination with other metals. PMID- 27678294 TI - Protective roles of SLC30A3 against endoplasmic reticulum stress via ERK1/2 activation. AB - Endoplasmic reticulum (ER) stress has been thought to be involved to neurodegenerative diseases such as Alzheimer's disease (AD) or Amyotrophic lateral sclerosis (ALS). The previous studies have shown that SLC30A3 level is decreased in prefrontal cortex of AD patients. In addition, we have shown that level of zinc (Zn) is increased in cerebrospinal fluid and SLC30A3 level is decreased in spinal cord of ALS patients. It was thought that both SLC30A3 and ER stress could be related to the cause of AD and ALS, however the relationship between ER stress and SLC30A3 has not been elucidated. Therefore we investigated that the role of SLC30A3 against ER stress. The level of SLC30A3 mRNA was significantly increased by tunicamycin treatment in human neuroblastoma cell line (SH-SY5Y) and human embryonic kidney cell line (HEK293). Cell viability under tunicamycin treatment was significantly decreased in SLC30A3 knockdown cells by siRNA in comparison with negative control (NC) cells. Cleaved caspase-3 level was significantly increased in SLC30A3 knockdown cells, not in NC cells. These results showed that SLC30A3 has a protective role to ER stress-induced toxicities. The previous study has shown that SLC30A3 protect cells from oxidative stress in ERK1/2 signal dependent manner, thus we determined the activity of ERK1/2 in SLC30A3 knockdown cells under ER stress condition. The level of ERK1/2 phosphorylation was significantly increased by tunicamycin treatment in NC cells, not in SLC30A3 knockdown cells. The ERK1/2 pathway is thought to have an association with defensive effects of SLC30A3 on cellular stress such as ER stress. In conclusion, this study suggested that SLC30A3 is supposed to play a protective role against ER stress, which is related to ERK1/2 activation. PMID- 27678295 TI - Phase II study of Vigil(r) DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. AB - OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS). METHODS: This is a Phase II crossover trial of Vigil (1.0*107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer patients achieving cCR (normal imaging, CA 125<=35units/ml, physical exam, and no symptoms suggestive of the presence of active disease) following primary surgical debulking and carboplatin/paclitaxel adjuvant or neoadjuvant chemotherapy. Patients received Vigil or standard of care during the maintenance period. RESULTS: Forty-two patients were entered into trial, 31 received Vigil and 11 received standard of care. No>=Grade 3 toxicity related to product was observed. A marked induction of circulating activated T cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNgamma ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826days/median 604days in the Vigil arm from mean 481days/median 377days in the control arm, p=0.033). CONCLUSION: In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil. PMID- 27678296 TI - Sexual health of endometrial cancer survivors before and after a physical activity intervention: A retrospective cohort analysis. AB - OBJECTIVE: Sexual dysfunction is common in endometrial cancer survivors (ECS). Our group previously tested a six-month exercise intervention in ECS. We performed a secondary analysis to determine intervention's impact on sexual health. METHODS: We studied 100 post-treatment Stage I-IIIa sedentary ECS who participated in a non-controlled, single-arm, home-based exercise intervention utilizing telephone counseling, printed material, and pedometers. Quality-of-life and physical activity measures were collected at baseline and six months. Sexual function (SF) and sexual interest (SI) scores were extracted from the QLACS questionnaire. RESULTS: Baseline SF and SI were lower in survivors with less than a four-year college degree (P<0.001). Baseline SI was higher in survivors who were married or living with a significant other (P=0.012). No significant differences in SF or SI were observed based on obesity status, race, time since diagnosis, or treatment type. Post-intervention, mean SF score improved (P=0.002), 51% of participants had improved SI, and 43% had improved SF. When controlled for age and time since diagnosis, a one-hour increase in weekly physical activity was associated with a 6.5% increased likelihood of improved SI (P=0.04). Increased physical activity was not associated with improved SF. CONCLUSIONS: Although causation cannot be determined in this study, the correlation between receipt of an exercise intervention and improved sexual health for ECS is a novel finding. This finding suggests a role for physical activity as a strategy to improve the sexual health of ECS, which our group is examining in a larger prospective study. PMID- 27678298 TI - Study of the Kidney Tumor-Parenchymal Interface after Neoadjuvant Treatment with Axitinib for Locally Advanced Clear Cell Renal Cell Carcinoma: Matched Analysis from a Phase II Trial. AB - PURPOSE: The aim of this study was to evaluate histological changes in the tumor parenchymal interface in clear cell renal cell carcinoma after neoadjuvant axitinib treatment. MATERIALS AND METHODS: We obtained clinical and pathology materials from 23 patients with clear cell renal cell carcinoma treated with neoadjuvant axitinib in a phase II clinical trial and from 23 matched patients with clear cell renal cell carcinoma who underwent upfront surgery. Histology of the tumor pseudocapsule and the peritumor kidney parenchymal change was evaluated and compared between the 2 cohorts. RESULTS: A tumor pseudocapsule was noted in all 23 patients who received neoadjuvant axitinib and in all 23 control patients. Most pseudocapsules were noncontinuous and only partially covered the tumor, including in 17 of 23 axitinib cases (74%) and 19 of 23 controls (83%). In axitinib cases the median thickness of the intrarenal and extrarenal pseudocapsule was 1.4 and 2.4 mm, respectively, which was significantly thicker than in control cases (intrarenal p = 0.0008 and extrarenal p <0.0001). The thickness of the pseudocapsule in axitinib treated cases was more frequently irregular compared to that in controls (16 of 23 or 70% and 9 of 23 or 39%, respectively, p = 0.0746). Inflammation, nephrosclerosis, glomerulosclerosis and arteriosclerosis decreased with increasing distance from the tumor edge in the neoadjuvant axitinib and control groups. CONCLUSIONS: The tumor pseudocapsule becomes irregularly thick after neoadjuvant axitinib therapy. Although axitinib likely evokes a strong fibrous reaction in the tumor-parenchymal interface, it does not affect the frequency of infiltrative tumor invasion to the outside of the pseudocapsule or the degree of atrophic/inflammatory change in tissue surrounding the tumor. These findings support the notion that partial nephrectomy could be safely done in well selected patients after neoadjuvant axitinib. PMID- 27678297 TI - Return of naturally sourced Pb to Atlantic surface waters. AB - Anthropogenic emissions completely overwhelmed natural marine lead (Pb) sources during the past century, predominantly due to leaded petrol usage. Here, based on Pb isotope measurements, we reassess the importance of natural and anthropogenic Pb sources to the tropical North Atlantic following the nearly complete global cessation of leaded petrol use. Significant proportions of up to 30-50% of natural Pb, derived from mineral dust, are observed in Atlantic surface waters, reflecting the success of the global effort to reduce anthropogenic Pb emissions. The observation of mineral dust derived Pb in surface waters is governed by the elevated atmospheric mineral dust concentration of the North African dust plume and the dominance of dry deposition for the atmospheric aerosol flux to surface waters. Given these specific regional conditions, emissions from anthropogenic activities will remain the dominant global marine Pb source, even in the absence of leaded petrol combustion. PMID- 27678300 TI - Pediatric Renal Angiomyolipomas in Tuberous Sclerosis Complex. AB - PURPOSE: Tuberous sclerosis complex is a genetic disorder characterized by the growth of hamartomas in multiple organs. Up to 80% of patients with tuberous sclerosis complex will have at least 1 angiomyolipoma in their lifetime. We describe the incidence and natural history of angiomyolipoma in a pediatric tuberous sclerosis complex population and analyze tumor growth to determine optimal renal imaging intervals in an effort to improve counseling, treatment and followup. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with tuberous sclerosis complex from 2004 to 2014. Patients were included if they had a clinical or genetic diagnosis of tuberous sclerosis complex and had undergone at least 1 renal imaging study. RESULTS: A total of 145 patients were analyzed. Median age was 14 years (range 0 to 28). Overall incidence of angiomyolipoma was 50.3%. Median age at first angiomyolipoma detection was 11 years (range 2 to 26). Median yearly angiomyolipoma growth rate stratified by age at first detection was 0.0 mm for patients 0 to 6 years old, 0.9 mm for those 7 to 11 years old, 2.5 mm for those 12 to 16 years old and 1.8 mm for those 17 years old or older. Median yearly angiomyolipoma growth rate stratified by tumor size at first detection was 0.1 mm for tumors 0.6 to 0.9 cm, 1.8 mm for those 1.0 to 1.9 cm and 4.3 mm for those 2.0 to 2.9 cm. A total of 35 patients (24.1%) received mTOR (mammalian target of rapamycin) inhibitors. Eight patients underwent a total of 13 surgical interventions, of whom 2 had previously been treated with mTOR inhibitors. Median patient age at surgical intervention was 18.0 years and median angiomyolipoma size was 5.0 cm. CONCLUSIONS: Angiomyolipoma growth in children with tuberous sclerosis complex can be rapid and unpredictable. We recommend yearly renal ultrasound in all patients with tuberous sclerosis complex, with consideration of magnetic resonance imaging in those at risk for rapid growth and future intervention (ie those older than 11 years and/or those with renal angiomyolipomas larger than 2 cm). PMID- 27678299 TI - Nocturnal Polyuria in Older Women with Urge Urinary Incontinence: Role of Sleep Quality, Time in Bed and Medications Used. AB - PURPOSE: Nocturia is common and bothersome in older adults, especially those who are also incontinent. Since nocturnal polyuria is a major contributor, we examined factors associated with nocturnal polyuria in this population to identify those possibly amenable to intervention. MATERIALS AND METHODS: We analyzed baseline data from 2 previously completed studies of urge urinary incontinence. The studies involved 284 women (mean age +/- SD 72.9 +/- 7.9 years) who also completed 3-day voiding diaries. Participants with a nocturnal polyuria index greater than 33% were categorized as having nocturnal polyuria (nocturnal polyuria index = nocturnal urinary volume per 24-hour urine volume). Associations between nocturnal polyuria and various demographic, clinical and sleep related parameters were determined. RESULTS: Overall 55% of the participants had nocturnal polyuria. Multivariable regression analysis revealed that age, body mass index, use of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, time spent in bed and duration of first uninterrupted sleep were independent correlates of nocturnal polyuria. Participants with a larger nocturnal excretion reported a shorter duration of uninterrupted sleep before first awakening to void and worse sleep quality despite spending similar time in bed. CONCLUSIONS: Body mass index, use of angiotensin converting enzyme inhibitor/angiotensin receptor blockers, time in bed and duration of uninterrupted sleep before first awakening to void are independently associated with nocturnal polyuria in older women with urge urinary incontinence, and are potentially modifiable. These findings also confirm the association between sleep and nocturnal polyuria. Further studies should explore whether interventions to reduce nocturnal polyuria and/or increase the duration of uninterrupted sleep before first awakening to void would help to improve sleep quality in this population and thereby reduce or eliminate the need for sedative hypnotics. PMID- 27678301 TI - Smart environment architecture for emotion detection and regulation. AB - This paper introduces an architecture as a proof-of-concept for emotion detection and regulation in smart health environments. The aim of the proposal is to detect the patient's emotional state by analysing his/her physiological signals, facial expression and behaviour. Then, the system provides the best-tailored actions in the environment to regulate these emotions towards a positive mood when possible. The current state-of-the-art in emotion regulation through music and colour/light is implemented with the final goal of enhancing the quality of life and care of the subject. The paper describes the three main parts of the architecture, namely "Emotion Detection", "Emotion Regulation" and "Emotion Feedback Control". "Emotion Detection" works with the data captured from the patient, whereas "Emotion Regulation" offers him/her different musical pieces and colour/light settings. "Emotion Feedback Control" performs as a feedback control loop to assess the effect of emotion regulation over emotion detection. We are currently testing the overall architecture and the intervention in real environments to achieve our final goal. PMID- 27678302 TI - Adiponectin protects the rats liver against chronic intermittent hypoxia induced injury through AMP-activated protein kinase pathway. AB - This study was performed to assess the effect of chronic intermittent hypoxia (CIH) on the liver, the associated mechanisms and the potential therapeutic roles of adiponectin (Ad). Sixty rats were randomly assigned to four groups: the normal control (NC), NC and Ad supplement (NC + Ad), CIH, and CIH and Ad supplement (CIH + Ad) groups. The rats in the CIH and CIH + Ad groups were exposed to a hypoxic environment for 4 months. Rats in the NC + Ad and CIH + Ad groups were also treated with an intravenous injection of Ad (10 ug), twice a week. The plasma levels of hepatic enzymes, serum triglyceride, liver triglyceride, fasting blood glucose and hepatic cell apoptosis in hepatic tissue, were higher in the CIH group than in the NC and NC + Ad groups. However, the Ad supplementation in the CIH + Ad group rescued the hepatic tissue insult by activating the AMP-activated protein kinase (AMPK) pathway. In conclusion, Ad could protect against CIH induced hepatic injury partly through the AMPK pathway. PMID- 27678303 TI - Erianin inhibits high glucose-induced retinal angiogenesis via blocking ERK1/2 regulated HIF-1alpha-VEGF/VEGFR2 signaling pathway. AB - Erianin is a natural compound found in Dendrobium chrysotoxum Lindl. Diabetic retinopathy (DR) is a serious and common microvascular complication of diabetes. This study aims to investigate the inhibitory mechanism of erianin on retinal neoangiogenesis and its contribution to the amelioration of DR. Erianin blocked high glucose (HG)-induced tube formation and migration in choroid-retinal endothelial RF/6A cells. Erianin inhibited HG-induced vascular endothelial growth factor (VEGF) expression, hypoxia-inducible factor 1-alpha (HIF-1alpha) translocation into nucleus and ERK1/2 activation in RF/6A and microglia BV-2 cells. MEK1/2 inhibitor U0126 blocked HG-induced HIF-1alpha and ERK1/2 activation in both above two cells. In addition, erianin abrogated VEGF-induced angiogenesis in vitro and in vivo, and also inhibited VEGF-induced activation of VEGF receptor 2 (VEGFR2) and its downstream cRaf-MEK1/2-ERK1/2 and PI3K-AKT signaling pathways in RF/6A cells. Furthermore, erianin reduced the increased retinal vessels, VEGF expression and microglia activation in streptozotocin (STZ)-induced hyperglycemic and oxygen-induced retinopathy (OIR) mice. In conclusion, our results demonstrate that erianin inhibits retinal neoangiogenesis by abrogating HG-induced VEGF expression by blocking ERK1/2-mediated HIF-1alpha activation in retinal endothelial and microglial cells, and further suppressing VEGF-induced activation of VEGFR2 and its downstream signals in retinal endothelial cells. PMID- 27678305 TI - Fractal zone plate beam based optical tweezers. AB - We demonstrate optical manipulation with an optical beam generated by a fractral zone plate (FZP). The experimental results show that the FZP beam can simultaneously trap multiple particles positioned in different focal planes of the FZP beam, owing to the multiple foci and self-reconstruction property of the FZP beam. The FZP beam can also be used to construct three-dimensional optical tweezers for potential applications. PMID- 27678304 TI - Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment. AB - In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create a dual matrix architecture that extended in a continuous manner, thus allowing invasion from one 3D matrix to another, and (2) establish distinct regions of tumor and stroma cell/ECM compositions, with a clearly demarcated tumor invasion front, thus allowing us to quantitatively analyze progression of cancer cells into the stroma at a tissue or single-cell level. We showed significantly enhanced cancer cell invasion in response to a transient gradient of epidermal growth factor (EGF). 3D tracking at the single-cell level displayed increased migration speed and persistence. Subsequently, we analyzed changes in expression of EGF receptors, cell aspect ratio, and protrusive activity. These findings show the unique ability of our model to quantitatively analyze 3D chemotactic invasion, both globally by tracking the progression of the invasion front, and at the single-cell level by examining changes in cellular behavior and morphology using high-resolution imaging. Taken together, we have shown a novel model recapitulating 3D tumor stroma interactions for studies of real-time cell invasion and morphological changes within a single platform. PMID- 27678306 TI - Dental caries, fluorosis, oral health determinants, and quality of life in adolescents. AB - OBJECTIVE: This study aimed to assess the extent to which dental caries and fluorosis, in addition to sociodemographic and oral health behavior determinants, impact the oral health-related quality of life (OHRQoL) of adolescents. METHODS: All adolescents attending from sixth to eighth grades in the Region of Itapoa, Federal District of Brazil (n = 1122), were screened, and 618 10-15-year-olds were selected. Parents answered a questionnaire about their family's socioeconomic status. Adolescents answered a questionnaire about demographic and oral health behavior determinants in addition to the Child Perception Questionnaire. RESULTS: Cavitated dentine lesions and fluorosis were observed in 39.5 and 48.5 %, respectively. The outcome was a high score on OHRQoL (median split >9). The prevalence of adolescents with at least one domain being impacted "often" or "every day/almost every day" was 34.8 %. Adolescents with tooth brushing frequency <=once per day and with moderate or severe cavitated dentine lesions reported a significant impact on their OHRQoL (p = 0.002; p = 0.001). Fluorosis did not impact daily life performances (p = 0.545). CONCLUSION: Increased impact on OHRQoL was related to the severity of cavitated dentine lesions, but fluorosis resulting from combined fluoride exposure from early ages was not of concern for the adolescents. CLINICAL RELEVANCE: Combined fluoride exposure from fluoridated drinking water, consumption of food prepared with fluoridated water, and daily twice brushing with conventional fluoride toothpaste from early ages may be recommended to control caries progression at population level without impact on OHRQoL. This information is particularly relevant for supporting oral health police for disadvantaged populations. PMID- 27678307 TI - Quantitative Proteomics Reveals the Defense Response of Wheat against Puccinia striiformis f. sp. tritici. AB - Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is considered one of the most aggressive diseases to wheat production. In this study, we used an iTRAQ-based approach for the quantitative proteomic comparison of the incompatible Pst race CYR23 in infected and non-infected leaves of the wheat cultivar Suwon11. A total of 3,475 unique proteins were identified from three key stages of interaction (12, 24, and 48 h post-inoculation) and control groups. Quantitative analysis showed that 530 proteins were differentially accumulated by Pst infection (fold changes >1.5, p < 0.05). Among these proteins, 10.54% was classified as involved in the immune system process and stimulus response. Intriguingly, bioinformatics analysis revealed that a set of reactive oxygen species metabolism-related proteins, peptidyl-prolyl cis-trans isomerases (PPIases), RNA-binding proteins (RBPs), and chaperonins was involved in the response to Pst infection. Our results were the first to show that PPIases, RBPs, and chaperonins participated in the regulation of the immune response in wheat and even in plants. This study aimed to provide novel routes to reveal wheat gene functionality and better understand the early events in wheat-Pst incompatible interactions. PMID- 27678308 TI - Design and Testing of BACRA, a Web-Based Tool for Middle Managers at Health Care Facilities to Lead the Search for Solutions to Patient Safety Incidents. AB - BACKGROUND: Lack of time, lack of familiarity with root cause analysis, or suspicion that the reporting may result in negative consequences hinder involvement in the analysis of safety incidents and the search for preventive actions that can improve patient safety. OBJECTIVE: The aim was develop a tool that enables hospitals and primary care professionals to immediately analyze the causes of incidents and to propose and implement measures intended to prevent their recurrence. METHODS: The design of the Web-based tool (BACRA) considered research on the barriers for reporting, review of incident analysis tools, and the experience of eight managers from the field of patient safety. BACRA's design was improved in successive versions (BACRA v1.1 and BACRA v1.2) based on feedback from 86 middle managers. BACRA v1.1 was used by 13 frontline professionals to analyze incidents of safety; 59 professionals used BACRA v1.2 and assessed the respective usefulness and ease of use of both versions. RESULTS: BACRA contains seven tabs that guide the user through the process of analyzing a safety incident and proposing preventive actions for similar future incidents. BACRA does not identify the person completing each analysis since the password introduced to hide said analysis only is linked to the information concerning the incident and not to any personal data. The tool was used by 72 professionals from hospitals and primary care centers. BACRA v1.2 was assessed more favorably than BACRA v1.1, both in terms of its usefulness (z=2.2, P=.03) and its ease of use (z=3.0, P=.003). CONCLUSIONS: BACRA helps to analyze incidents of safety and to propose preventive actions. BACRA guarantees anonymity of the analysis and reduces the reluctance of professionals to carry out this task. BACRA is useful and easy to use. PMID- 27678311 TI - Foreword. PMID- 27678310 TI - Controllability and hippocampal activation during pain expectation in fibromyalgia syndrome. AB - To examine the role of perceived control in pain perception, fibromyalgia patients and healthy controls participated in a reaction time experiment under different conditions of pain controllability. No significant differences between groups were found in pain intensity and unpleasantness ratings. However, during the expectation of uncontrollable pain, patients compared to controls showed higher hippocampal activation. In addition, hippocampal activity during the pain expectation period predicted activation of the posterior cingulate cortex (PCC), precuneus and hippocampus during pain stimulation in fibromyalgia patients. The increased activation of the hippocampus during pain expectation and subsequent activation of the PCC/precuneus during the lack of control phase points towards an influence of pain perception through heightening of alertness and anxiety responses to pain in fibromyalgia patients. PMID- 27678309 TI - Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens. AB - The identification of genes encoding a p53 family member and an Mdm2 ortholog in the ancient placozoan Trichoplax adhaerens advocates for the evolutionary conservation of a pivotal stress-response pathway observed in all higher eukaryotes. Here, we recapitulate several key functionalities ascribed to this known interacting protein pair by analysis of the placozoan proteins (Tap53 and TaMdm2) using both in vitro and cellular assays. In addition to interacting with each other, the Tap53 and TaMdm2 proteins are also able to respectively bind human Mdm2 and p53, providing strong evidence for functional conservation. The key p53-degrading function of Mdm2 is also conserved in TaMdm2. Tap53 retained DNA binding associated with p53 transcription activation function. However, it lacked transactivation function in reporter genes assays using a heterologous cell line, suggesting a cofactor incompatibility. Overall, the data supports functional roles for TaMdm2 and Tap53, and further defines the p53 pathway as an evolutionary conserved fulcrum mediating cellular response to stress. PMID- 27678312 TI - Cancer in Central and South America: Methodology. AB - Statistics on cancer incidence from Central and South American countries are scarce because of the small number of population-based cancer registries that continuously collect data. Similarly, comparable statistics on cancer mortality are sparse in spite of efforts made to improve coverage in the last decade. The aim of this study is to describe geographical patterns and trends in cancer incidence and mortality in Central and South America in the 21st century. The primary objective was to obtain the best quality cancer data available from each country within the region. Cancer incidence data were obtained from population based cancer registries within the region and, in countries where these did not exist, from hospital-based registries; national mortality data were obtained from the World Health Organization mortality database. Given the variability in data quality - mainly due to the age and development in maturity of the registries, an exhaustive review of the data was necessary in order to appropriately analyze, describe and interpret patterns of cancer incidence and mortality between countries and within cancer-specific sites. This paper presents the methods employed in the collection, quality control and analysis of the datasets received for the project. PMID- 27678313 TI - Female breast cancer in Central and South America. AB - RATIONALE AND OBJECTIVE: The burden of breast cancer has increased worldwide. Breast cancer mortality has been increasing in Central and South America (CSA) in the last few decades. We describe the current burden of breast cancer in CSA and review the current status of disease control. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence and mortality rates per 100,000 person-years for 2003-2007 and the estimated annual percentage change to describe time trends. RESULTS: In the most recent 5-year period, Argentina, Brazil, and Uruguay had the highest incidence rates (67.7-71.9) and Bolivia and El Salvador had the lowest (7.9-12.7). For most countries, mortality rates were <=12.3, except in Uruguay, Argentina and Cuba (14.9-20.5). Age-specific rates increased after the age of 40-50 years and reached a maximum after age 65 years (mean age at diagnosis 56-62 years). Most countries have developed national screening guidelines; however, there is limited capacity for screening. CONCLUSION: The geographic variation of breast cancer rates may be explained by differences in the prevalence of reproductive patterns, lifestyle factors, early detection, and healthcare access. Extending early-detection programs is challenging because of inequalities in healthcare access and coverage, limited funding, and inadequate infrastructure, and thus it may not be feasible. Given the current status of breast cancer in CSA, data generated by population-based cancer registries is urgently needed for effective planning for cancer control. PMID- 27678314 TI - Cervical cancer in Central and South America: Burden of disease and status of disease control. AB - RATIONALE AND OBJECTIVE: More than 20 years after cytology-based screening was introduced in Central and South America (CSA), cervical cancer remains a leading cause of cancer incidence and mortality in the region. Although several population-based registries exist in the region, few comprehensive analyses have been conducted to describe the status of cervical cancer control. METHODS: Population-based data from cancer registries in 13 countries and mortality data from 18 countries in CSA were analyzed. Standardized incidence and mortality rates were estimated and time trend analysis performed when information was available. In addition, a search of available data on HPV vaccination and cervical cancer screening was carried out. RESULTS: Cervical cancer incidence and mortality have decreased in some CSA countries, with an annual percentage change from -4.2 to -6.7 for incidence and -0.2 to -8.3 for mortality. In total, seven countries have age-standardized mortality rates over 10 per 100,000 women, generally corresponding to those with the lowest income levels. All countries have implemented screening programs with different extents of coverage and levels of organization. To date, nine countries have introduced HPV vaccination in national immunization programs. CONCLUSIONS: Despite incidence declines observed in some countries, cervical cancer mortality remained almost stable in most countries in the region. Decreases in mortality trends in Chile and Costa Rica are probably the result of early detection programs. Better organized programs might favor greater impact on cancer incidence and mortality, but technological developments offer more suitable opportunities for prevention and alternative approaches for screening of precancerous lesions. PMID- 27678315 TI - Prostate cancer burden in Central and South America. AB - RATIONALE AND OBJECTIVE: The incidence of prostate cancer has increased in Central and South America (CSA) in the last few decades. We describe the geographical patterns and trends of prostate cancer in CSA. METHODS: We obtained regional and national-level cancer incidence data from 48 population-based registries in 13 countries and nation-wide cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years for 2003-2007 and the estimated annual percent change (EAPC) to describe time trends. RESULTS: Prostate cancer was the most common cancer diagnosis and one of the leading causes of cancer deaths among males in most CSA countries. From 2003-2007, ASRs varied between countries (6-fold) and within countries (Brazil: 3-6-fold). French Guyana (147.1) and Brazil (91.4) had the highest ASRs whereas Mexico (28.9) and Cuba (24.3) had the lowest. ASMRs varied by 4-fold. Belize, Uruguay and Cuba (24.1-28.9) had the highest ASMRs while Peru, Nicaragua, and El Salvador (6.8 9.7) had the lowest. In Argentina, Brazil, Chile and Costa Rica prostate cancer incidence increased by 2.8-4.8% annually whereas mortality remained stable between 1997 and 2008. CONCLUSION: The geographic and temporal variation of prostate cancer rates observed in CSA may in part reflect differences in diagnostic and registration practices, healthcare access, treatment and death certification, and public awareness. The incidence of prostate cancer is expected to increase given recent early detection activities and increased public awareness; however, the impact of these factors on mortality remains to be elucidated. PMID- 27678316 TI - Descriptive epidemiology of brain and central nervous system cancers in Central and South America. AB - RATIONALE AND OBJECTIVE: Although malignant tumors of the brain and central nervous system (CNS) represent less than 3% of new cancer cases estimated worldwide, they cause significant morbidity and in the case of gliomas, the most common histological type, have a poor prognosis. We describe patterns and trends in brain and CNS incidence and mortality in Central and South America. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and mortality rates (ASMRs) per 100,000 person-years, and present incidence by histological subtypes. RESULTS: In general, incidence rates were higher in males than in females. The highest incidence ASRs were observed for Cuba (5.1 males, 3.6 females) in Central America, and for Brazil (6.4 males, 4.8 females) and Uruguay (6.2 and 4.0) in South America. Mortality rates closely followed the pattern of incidence rates. Argentina, Brazil and Chile showed increasing mortality trends, although these were not statistically significant. Glioma and unspecified tumors were the most common histological types, accounting for 55.4% and 32.8%, respectively. The proportion of microscopically verified diagnoses was 47-70% in most countries. CONCLUSION: Although incidence and mortality rates in general were low, some countries displayed high- to intermediate-level incidence rates; under-reporting and under-ascertainment of cases could contribute to the geographic variations observed. There is a need to improve both the ascertainment of cases and the accuracy of histological diagnosis. Monitoring of brain and CNS cancers along with etiological research remain priorities. PMID- 27678317 TI - Thyroid cancer burden in Central and South America. AB - RATIONALE AND OBJECTIVE: Incidence of thyroid cancer (TC) is rapidly increasing worldwide, but little is known about the TC burden in Central and South America (CSA). We describe the geographic patterns and trends of TC by sex in CSA. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and nationwide cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and age-standardized mortality rates (ASMRs) per 100,000 person-years. We calculated ASRs by histological subtype. We estimated the annual percentage change (EAPC) to describe time trends. RESULTS: Between CSA countries, TC incidence and mortality rates varied from 8-fold to 12 fold and from 2-fold to 5-fold, respectively. In 2003-2007, the highest TC ASRs in females and males were in Ecuador (16.0 and 3.5, respectively), Brazil (14.4 and 3.4), Costa Rica (12.6 and 2.1) and Colombia (10.7 and 2.5). The highest ASMRs were in Ecuador, Colombia, Mexico, Peru and Panama (0.68-0.91 in females and 0.41-0.48 in males). Papillary TC was the most commonly diagnosed histological subtype, following the same incidence pattern as overall TC. In Argentinean, Brazilian, Chilean and Costa Rican females TC incidence increased by 2.2-17.9% annually, and papillary TC increased by 9.1-15.0% annually, while mortality remained stable between 1997 and 2008. In males, trends in TC were stable. CONCLUSION: TC occurred more frequently in females than in males. The overall high incidence and low mortality of TC suggest identification of subclinical disease due to improved detection methods. PMID- 27678318 TI - Hodgkin lymphoma burden in Central and South America. AB - RATIONALE AND OBJECTIVE: Hodgkin lymphoma (HL) is largely curable owing to improvements in treatment since the 1960s; nevertheless, high mortality rates have been reported in Central and South America. We describe the current burden of HL in the Central and South American region. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, and national-level mortality data from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and age-standardized mortality rates (ASMRs) per 100,000 person-years for 2003-2007 and present distributions by histological subtype. RESULTS: HL incidence rates varied 7-fold in males and 11-fold in females (male-to-female ratio 1:1-2.5:1). The highest ASRs were seen Argentina, Brazil, Costa Rica (males), Cuba (males) and Uruguay (females), whereas the lowest were in Bolivia and El Salvador. ASMRs varied by 4-fold in males and 6-fold in females (male-to female ratio 1:1-4.3:1), with ASMRs <0.7 for most countries, except Cuba (>=1.0). In most countries, age-specific incidence rates of HL showed a bimodal pattern. Trends in HL in Argentina, Brazil, Chile, and Costa Rica remained stable in 1997 2008. Of all HL cases, 48% were unspecified as to histological subtype. Nodular sclerosis and mixed cellularity were the most frequent histologies. CONCLUSION: The geographic variation in HL across the region may in part reflect differences in data quality and coverage, and differences in the adoption of modern therapies and healthcare access. Our results highlight the need for high-quality data and increased coverage in order to provide vital guidance for future cancer control activities. PMID- 27678319 TI - The burden of non-Hodgkin lymphoma in Central and South America. AB - RATIONALE AND OBJECTIVE: The burden of non-Hodgkin lymphoma (NHL) has increased in some Central and South American countries. We describe the current patterns and trends in NHL incidence and mortality in Central and South America. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, and national-level cancer mortality data from the WHO mortality database for 18 countries. We estimated world population age standardized incidence rates (ASRs) and mortality rates (ASMRs) per 100,000 person-years for 2003-2007, and presented distributions by histological subtype. RESULTS: NHL incidence and mortality rates varied between countries by 2-8- and 6 fold, respectively. ASRs per 100,000 ranged from 1.4 to 10.9 among males and 1.3 9.2 among females. Corresponding ASMRs were between 0.5 and 4.8 among males and between 0.5 and 3.0 among females. The highest incidence was observed in Uruguay (males), Ecuador, Peru and Colombia (males). The highest mortality was seen in Uruguay and Costa Rica. Trends in NHL incidence and mortality in Argentina, Brazil, Chile and Costa Rica did not show marked changes. B-cell neoplasms and NHL not otherwise specified (NOS) accounted for 44% and 34% of all NHL cases. Diffuse large B-cell lymphoma, NOS, was the most frequent histological subtype. CONCLUSION: The geographic variations in NHL rates may partially reflect differences in registration practices, disease classification, diagnostic practice, and death certification quality. There is a need for high-quality data and improvements in the accuracy of NHL histological diagnosis. Given the expected increase in NHL, careful monitoring of rates remains a priority to guide cancer control programs. PMID- 27678320 TI - Cancer patterns and trends in Central and South America. AB - RATIONALE AND OBJECTIVE: Cancer burden is increasing in Central and South America (CSA). We describe the current burden of cancer in CSA. METHODS: We obtained regional and national-level cancer incidence data from 48 population-based registries (13 countries) and nation-wide cancer mortality data from the WHO (18 countries). We estimated world population age-standardized incidence and mortality rates per 100,000 person-years. RESULTS: The leading cancers diagnosed were prostate, lung, breast, cervix, colorectal, and stomach, which were also the primary causes of cancer mortality. Countries of high/very high human development index (HDI) in the region experienced a high burden of prostate and breast cancer while medium HDI countries had a high burden of stomach and cervical cancers. Between countries, incidence and mortality from all cancers combined varied by 2 3-fold. French Guyana, Brazil, Uruguay, and Argentina had the highest incidence of all cancers while Uruguay, Cuba, Argentina, and Chile had the highest mortality. Incidence of colorectum, prostate and thyroid cancers increased in Argentina, Brazil, Chile and Costa Rica from 1997 to 2008, while lung, stomach and cervical cancers decreased. CONCLUSION: CSA carries a double-burden of cancer, with elevated rates of infection- and lifestyle-related cancers. Encountered variation in cancer rates between countries may reflect differences in registration practices, healthcare access, and public awareness. Resource dependent interventions to prevent, early diagnose, and treat cancer remain an urgent priority. There is an overwhelming need to improve the quality and coverage of cancer registration to guide and evaluate future cancer control policies and programs. PMID- 27678321 TI - Cancer in Central and South America: Introduction. AB - Central and South American countries (including Cuba) are experiencing rapid socio-demographic and epidemiologic changes and the nature of health problems are undergoing transition from infectious to chronic diseases, including cancer. Countries are poorly prepared to respond effectively to the subsequent challenges posed by the new patterns of disease. Existing data delineating the number of cancer cases and the distribution of cancer types from each country in the region are sparse due to limitations on health information systems for recording incidence and mortality despite improvements made in recent years. There is an urgent need for reliable statistics on cancer to inform governmental entities responsible for cancer control in the region. We attempted to obtain the best available cancer data from each country located in the region to provide an overview of current geographic patterns of cancer incidence and mortality in the 21st century. PMID- 27678322 TI - Head and neck cancer burden and preventive measures in Central and South America. AB - RATIONALE AND OBJECTIVE: Central and South America comprise one of the areas characterized by high incidence rates for head and neck cancer. We describe the geographical and temporal trends in incidence and mortality of head and neck cancers in the Central and South American region in order to identify opportunities for intervention on the major identified risk factors: tobacco control, alcohol use and viral infections. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. Age standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years were estimated. RESULTS: Brazil had the highest incidence rates for oral and pharyngeal cancer in the region for both sexes, followed by Cuba, Uruguay and Argentina. Cuba had the highest incidence and mortality rates of laryngeal cancer in the region for males and females. Overall, males had rates about four times higher than those in females. Most countries in the region have implemented WHO recommendations for both tobacco and alcohol public policy control. CONCLUSION: Head and neck squamous-cell cancer (HNSCC) incidence and mortality rates in the Central and South America region vary considerably across countries, with Brazil, Cuba, French Guyana, Uruguay and Argentina experiencing the highest rates in the region. Males carry most of the HNSCC burden. Improvement and implementation of comprehensive tobacco and alcohol control policies as well as the monitoring of these factors are fundamental to prevention of head and neck cancers in the region. PMID- 27678323 TI - The burden of oesophageal cancer in Central and South America. AB - RATIONALE AND OBJECTIVE: Oesophageal cancer shows marked geographic variations and is one of the leading causes of cancer death worldwide. We described the burden of this malignancy in Central and South America. METHODS: Regional and national level incidence data were obtained from 48 population-based cancer registries in 13 countries. Mortality data were obtained from the WHO mortality database. Incidence of oesophageal cancer by histological subtype were available from high-quality population-based cancer registries. RESULTS: Males had higher incidence and mortality rates than females (male-to-female ratios: 2-6:1 and 2 5:1). In 2003-2007, the highest rates were in Brazil, Uruguay, Argentina and Chile. Mortality rates followed the incidence patterns. Incidence of oesophageal squamous cell carcinoma (SCC) was higher than adenocarcinoma (AC), except in females from Cuenca (Ecuador). SCC and AC incidence were higher in males than females, except in the Region of Antofagasta and Valdivia (Chile), Manizales (Colombia) and Cuenca (Ecuador). Incidence and mortality rates tended to decline in Argentina, Chile, Brazil (incidence) and Costa Rica from 1997 to 2008. CONCLUSION: The geographic variation and sex disparity in oesophageal cancer across Central and South America may reflect differences in the prevalence of tobacco smoking and alcohol consumption which highlights the need to implement and/or strengthen tobacco and alcohol control policies. Mate consumption, obesity, diet and Helicobacter pylori infection may also explain the variation in oesophageal cancer rates but these relationships should be evaluated. Continuous monitoring of oesophageal cancer rates is necessary to provide the basis for cancer prevention and control in the region. PMID- 27678324 TI - Stomach cancer burden in Central and South America. AB - RATIONALE AND OBJECTIVE: Stomach cancer mortality rates in Central and South America (CSA) are among the highest in the world. We describe the current burden of stomach cancer in CSA. METHODS: We obtained regional and national-level cancer incidence data from 48 population-based registries (13 countries) and nation-wide cancer deaths from WHO's mortality database (18 countries). We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 and estimated annual percent change to describe time trends. RESULTS: Stomach cancer was among the 5 most frequently diagnosed cancers and a leading cause of cancer mortality. Between CSA countries, incidence varied by 6-fold and mortality by 5-6-fold. Males had up to 3-times higher rates than females. From 2003 to 2007, the highest ASRs were in Chile, Costa Rica, Colombia, Ecuador, Brazil and Peru (males: 19.2-29.1, females: 9.7-15.1). The highest ASMRs were in Chilean, Costa Rican, Colombian and Guatemalan males (17.4-24.6) and in Guatemalan, Ecuadorian and Peruvian females (10.5-17.1). From 1997 to 2008, incidence declined by 4% per year in Brazil, Chile and Costa Rica; mortality declined by 3-4% in Costa Rica and Chile. 60-96% of all the cancer cases were unspecified in relation to gastric sub-site but, among those specified, non cardia cancers occurred 2-13-times more frequently than cardia cancers. CONCLUSION: The variation in rates may reflect differences in the prevalence of Helicobacter pylori infection and other risk factors. High mortality may additionally reflect deficiencies in healthcare access. The high proportion of unspecified cases calls for improving cancer registration processes. PMID- 27678325 TI - Burden of colorectal cancer in Central and South America. AB - RATIONALE AND OBJECTIVE: The colorectal cancer (CRC) burden is increasing in Central and South American due to an ongoing transition towards higher levels of human development. We describe the burden of CRC in the region and review the current status of disease control. METHODS: We obtained regional- and national level incidence data from 48 population-based cancer registries in 13 countries, as well as cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years for 2003-2007 and the estimated annual percentage change for 1997-2008. RESULTS: The CRC rate in males was 1-2 times higher than that in females. In 2003-2007, the highest ASRs were seen in Uruguayan, Brazilian and Argentinean males (25.2-34.2) and Uruguayan and Brazilian females (21.5 24.7), while El Salvador had the lowest ASR in both sexes (males: 1.5, females: 1.3). ASMRs were<10 for both sexes, except in Uruguay, Cuba and Argentina (10.0 17.7 and 11.3-12.0). CRC incidence is increasing in Chilean males. Most countries have national screening guidelines. Uruguay and Argentina have implemented national screening programs. CONCLUSION: Geographic variation in CRC and sex gaps may be explained by differences in the prevalence of obesity, physical inactivity, diet, smoking and alcohol consumption, early detection, and cancer registration practices. Establishing optimal CRC screening programs is challenging due to lack of healthcare access and coverage, funding, regional differences and inadequate infrastructure, and may not be feasible. Given the current status of CRC in the region, data generated by population-based cancer registries is crucial for cancer control planning. PMID- 27678326 TI - Burden of gallbladder cancer in Central and South America. AB - RATIONALE AND OBJECTIVE: Gallbladder carcinoma (GBC) is a rare neoplasm yet it is the most common malignancy of the biliary tract and its prognosis is poor. Incidence of GBC is high in some areas of Central and South America and the Caribbean. We described the current burden of GBC in Central and South America (CSA). METHODS: We obtained GBC incidence data from 48 population-based cancer registries in 13 countries in CSA, and national level cancer death data from the WHO mortality data base for 18 countries. We estimated World population age standardized incidence and mortality rates per 100,000 persons-years, including distribution and incidence rates by anatomic subsite. RESULTS: GBC rates were the highest in countries located in the Andean region. In 2003-2007, Chile had the highest incidence and mortality rates in CSA (17.1 and 12.9 in females and 7.3 and 6.0 in males, respectively). Females had higher GBC rates than males. The most frequently diagnosed anatomic subsite was gallbladder (60%). Unspecified subsite represented 21% of all cases. Trends in incidence and mortality of GBC remained unchanged in Argentina, Brazil, Chile and Costa Rica in 1998-2008. CONCLUSION: GBC rates varied extensively across the CSA region reflecting, in part, differences in data quality, coverage and healthcare access. Chile had the highest GBC rates in CSA and the world. The large proportion of unspecified cases indicates low precision in diagnosis/registration and highlights the need to promote and improve cancer registration in the region to better understand the burden of GBC in CSA. PMID- 27678327 TI - Descriptive epidemiology of lung cancer and current status of tobacco control measures in Central and South America. AB - RATIONALE AND OBJECTIVE: Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the world. In Central and South America lung cancer is now one of most frequent cancers and the leading cause of cancer related death in both sexes. We describe patterns and trends in lung cancer incidence and mortality in Central and South America and give a brief overview of the current status of tobacco control measures based on the most recent MPOWER report. METHODS: We obtained regional and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age standardized incidence and mortality rates per 100,000 person-years. Incidence of lung cancer by histological subtype were only available from high-quality population-based cancer registries for the period 2003-2007. RESULTS: The highest incidence and mortality rates in the region were seen among males in Argentina, Cuba, Chile and Uruguay. Adenocarcinoma was the most frequent histological type overall, though squamous carcinoma was more frequent in Antofagasta-Chile and Villa Clara-Cuba. Smoke-free policies and warnings are widely implemented tobacco control measures; cessation is offered but the costs are not covered by health systems in the majority of countries. CONCLUSION: The high burden of lung cancer in the region highlights the need to improve long term information and strengthen current tobacco control policies including aggressive taxing measures and supporting smoking cessation in order to achieve the targeted reductions in smoking prevalence. PMID- 27678328 TI - Pull-out strength of cemented solid versus fenestrated pedicle screws in osteoporotic vertebrae. AB - OBJECTIVES: Cement augmentation of pedicle screws could be used to improve screw stability, especially in osteoporotic vertebrae. However, little is known concerning the influence of different screw types and amount of cement applied. Therefore, the aim of this biomechanical in vitro study was to evaluate the effect of cement augmentation on the screw pull-out force in osteoporotic vertebrae, comparing different pedicle screws (solid and fenestrated) and cement volumes (0 mL, 1 mL or 3 mL). MATERIALS AND METHODS: A total of 54 osteoporotic human cadaver thoracic and lumbar vertebrae were instrumented with pedicle screws (uncemented, solid cemented or fenestrated cemented) and augmented with high viscosity PMMA cement (0 mL, 1 mL or 3 mL). The insertion torque and bone mineral density were determined. Radiographs and CT scans were undertaken to evaluate cement distribution and cement leakage. Pull-out testing was performed with a material testing machine to measure failure load and stiffness. The paired t-test was used to compare the two screws within each vertebra. RESULTS: Mean failure load was significantly greater for fenestrated cemented screws (+622 N; p ? 0.001) and solid cemented screws (+460 N; p ? 0.001) than for uncemented screws. There was no significant difference between the solid and fenestrated cemented screws (p = 0.5). In the lower thoracic vertebrae, 1 mL cement was enough to significantly increase failure load, while 3 mL led to further significant improvement in the upper thoracic, lower thoracic and lumbar regions. CONCLUSION: Conventional, solid pedicle screws augmented with high-viscosity cement provided comparable screw stability in pull-out testing to that of sophisticated and more expensive fenestrated screws. In terms of cement volume, we recommend the use of at least 1 mL in the thoracic and 3 mL in the lumbar spine.Cite this article: C. I. Leichtle, A. Lorenz, S. Rothstock, J. Happel, F. Walter, T. Shiozawa, U. G. Leichtle. Pull-out strength of cemented solid versus fenestrated pedicle screws in osteoporotic vertebrae. Bone Joint Res 2016;5:419-426. PMID- 27678329 TI - Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. AB - OBJECTIVES: Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. MATERIALS AND METHODS: We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer's solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. RESULTS: The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). CONCLUSIONS: This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials.Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427-435. DOI: 10.1302/2046 3758.59.BJR-2016-0108.R1. PMID- 27678330 TI - Cross-talk between Human Papillomavirus Oncoproteins and Hedgehog Signaling Synergistically Promotes Stemness in Cervical Cancer Cells. AB - Viral oncoproteins E6/E7 play key oncogenic role in human papillomavirus (HPV) mediated cervical carcinogenesis in conjunction with aberrant activation of cellular signaling events. GLI-signaling has been implicated in metastasis and tumor recurrence of cervical cancer. However, the interaction of GLI-signaling with HPV oncogenes is unknown. We examined this relationship in established HPV positive and HPV-negative cervical cancer cell lines using specific GLI inhibitor, cyclopamine and HPVE6/E7 siRNAs. Cervical cancer cell lines showed variable expression of GLI-signaling components. HPV16-positive SiHa cells, overexpressed GLI1, Smo and Patch. Inhibition by cyclopamine resulted in dose dependent reduction of Smo and GLI1 and loss of cell viability with a higher magnitude in HPV-positive cells. Cyclopamine selectively downregulated HPVE6 expression and resulted in p53 accumulation, whereas HPVE7 and pRb level remained unaffected. siRNA-mediated silencing of HPV16E6 demonstrated reduced GLI1 transcripts in SiHa cells. Cervical cancer stem-like cells isolated by side population analysis, displayed retention of E6 and GLI1 expression. Fraction of SP cells was reduced in cyclopamine-treated cultures. When combined with E6 silencing cyclopamine resulted in loss of SP cell's sphere-forming ability. Co inhibition of GLI1 and E6 in cervical cancer cells showed additive anti-cancer effects. Overall, our data show existence of a cooperative interaction between GLI signaling and HPVE6. PMID- 27678332 TI - A comparison of five approaches to decision-making for a first clinical trial of efficacy. AB - The first trial of clinical efficacy is an important step in the development of a compound. Such a trial gives the first indication of whether a compound is likely to have the efficacy needed to be successful. Good decisions dictate that good compounds have a large probability of being progressed and poor compounds have a large probability of being stopped. In this paper, we consider and contrast five approaches to decision-making that have been used. To illustrate the use of the five approaches, we conduct a comparison for two plausible scenarios with associated assumptions for sample sizing. The comparison shows some large differences in performance characteristics of the different procedures. Which decision-making procedures and associated performance characteristics are preferred will depend on the focus of interest and the decision maker's attitude to risk. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27678331 TI - Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth. AB - Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (<100 nmol/L); in addition, the IC50s were lower than that of lapatinib and dacomitinib. Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK. Irreversible inhibition of HER2 and EGFR in breast cancer cells was established after 30-minute incubation above 100 nmol/L or following 2-hour incubation at lower concentrations. Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction. The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK. Xenograft studies with HER2+ MDA-MB-453 and BT-474 cells in mice in conjunction with determination of pharmacokinetics demonstrated significant exposure-dependent inhibition of growth and key signaling molecules at levels that are clinically achievable. Ibrutinib's unique dual spectrum of activity against both TEC family and ERBB kinases suggests broader applications of ibrutinib in oncology. Mol Cancer Ther; 15(12); 2835-44. (c)2016 AACR. PMID- 27678333 TI - Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer. AB - Fusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The objective of this study was to identify Fn infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC. PMID- 27678334 TI - Attitudes among dentists and dental hygienists towards extended scope and independent practice of dental hygienists. AB - AIMS: Attitudes of dentists and dental hygienists towards extended scope and independent dental hygiene practice are described in several studies, but the results are heterogenous. The purpose of this systematic review was to compare the attitudes of dentists and dental hygienists towards extended scope and independent dental hygiene practice. METHODS: PubMed, AMED and CINAHL were screened by two independent assessors to identify relevant studies. Only quantitative studies that reported the percentages of dentists' and dental hygienists' attitude towards extended scope and independent dental hygiene practice were included. The random-effects model was used to synthesise possible heterogenous influences. RESULTS: Meta proportions with regard to a positive attitude towards extended scope of practice are 0.54 for dentists and 0.81 for dental hygienists. Meta proportions of a positive attitude towards independent practice are 0.14 for dentists and 0.59 for dental hygienists. A meta analysis with regard to negative attitudes could only be performed on extended scope of practice and did not reveal a difference between the two professions. We obtained homogeneous outcomes of the studies included regarding negative attitudes of dentists . A minority of dentists hold negative attitudes towards extended scope of dental hygiene practice. Study outcomes regarding negative attitudes of dental hygienists were heterogeneous. CONCLUSIONS: Positive attitudes are present among a majority of dentists and dental hygienists with regard to extended scope of dental hygiene practice, while for independent dental hygiene practice this holds for a minority of dentists and a majority of dental hygienists. PMID- 27678335 TI - Mechanical properties of borophene films: a reactive molecular dynamics investigation. AB - The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1-0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young's modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young's modulus and fracture stress of these five sheets appear in the range 63-136 N m(-1) and 12-19 N m(-1), respectively. In addition, the strains at tensile strength are in the ranges of 9%-14%, 11%-19%, and 10%-16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures. PMID- 27678338 TI - Genome sequencing identifies a large deletion at 13q32.1 as the cause of microcoria and childhood-onset glaucoma. PMID- 27678336 TI - Heterogeneity of respiratory distress syndrome: risk factors and morbidity associated with early and late gestation disease. AB - BACKGROUND: Although respiratory distress syndrome (RDS) is considered a disease of prematurity, there is evidence to suggest heterogeneity between early and late gestation RDS. We examined the epidemiologic features of RDS occurring at early and late gestation. METHODS: We conducted a retrospective cohort study including live births in the United States in 2005-06, with information obtained from the National Center for Health Statistics. Early (<32 weeks) and late gestation RDS (>=39 weeks) were contrasted in terms of risk factors and associations with pregnancy complications, obstetric intervention and co-morbidity. Logistic regression was used to quantify the effects of risk factors, while other associations were quantified descriptively. RESULTS: There were 27,971 RDS cases, yielding an incidence of 6.4 per 1000 live births. Early and late gestation RDS differed in terms of risk factors, with factors such as multi-fetal gestation more strongly associated with early (adjusted odds ratio [aOR] 11.6, 95 % confidence interval 11.0-12.2) compared with late gestation RDS (aOR 3.66, 95 % confidence interval 2.68-4.98). The morbidity correlates of early and late gestation RDS also differed substantially; neonatal seizures were less strongly associated with early (OR 5.90, 95 % confidence interval 3.67-9.47) compared with late gestation RDS (OR 33.1, 95 % confidence interval 27.2-40.2), while meconium aspiration syndrome was not significantly associated with early gestation RDS (OR 1.87, 95 % confidence interval 0.94-3.72) and very strongly associated with late gestation RDS (OR 39.8, 95 % confidence interval 34.7-45.6). CONCLUSIONS: Differences in risk factors and morbidity correlates of early and late gestation RDS suggest that these entities represent two distinct diseases. PMID- 27678339 TI - Buttonhole Cannulation of the AV Fistula: A Critical Analysis of the Technique. AB - As a consequence of the central role of the arteriovenous fistula for dialysis (AVF) in the clinical management of the dialysis patient the necessity to limit the puncture-related complications to extend as much as possible the life of the vascular access. Accordingly, the AVF needling technique has gained growing attention. Alongside the traditional rope ladder (RL) puncture method, the buttonhole technique (BH) is increasingly popular; this technique employs the same cannulation sites of AVF in every dialysis associated with the use of dull needles to minimize vessels damage. The BH technique, utilized only for native AVF, is considered an appropriate alternative to the RL and is now recommended by several scientific societies for its reported benefits such as: AVF greater ease of cannulation, less pain, faster hemostasis and less tendency to the creation of aneurysms and hematomas. The use of BH is especially recommended in cases in which the RL is problematic with short or winding venous sections and in home dialysis in which the patient performs the needling. However recent evidence in literature, countering these theoretical advantages, indicates that the BH technique appears to be closely related to an increased risk of local and systemic infections. Furthermore, the purported benefits of BH have not held up under closer examination. PMID- 27678341 TI - Editorial (Thematic Issue: Targeting Conformational Diseases with Natural and Pharmacological Chaperones). PMID- 27678340 TI - Production of infectious HCV genotype 1b virus in cell culture using a novel Set of adaptive mutations. AB - BACKGROUND: Despite the high prevalence of genotype 1b hepatitis C virus (HCV) among patients, a cell culture system that permits entire viral life cycle of genotype 1b isolates is limited. To develop a cell-cultured hepatitis C virus (HCVcc) of genotype 1b, the proper combination of HCV genomic variants and host cells is essential. HCV genomes isolated from patients with distinctive symptoms may provide the variants required to establish an HCVcc of genotype 1b. RESULTS: We first established subgenomic replicons in Huh7 cells using HCV cDNAs isolated from two patients: one with fulminant hepatitis after liver transplantation (TPF1) and another with acute hepatitis and moderate symptoms (sAH). Replicons established from TPF1 and sAH showed mutations in NS4B and in NS3 and NS5A, respectively. Using these replication machineries, we constructed HCV genomic RNAs for each isolate. Virus infectivity was evaluated by a focus-forming assay, which is dependent on the intracellular expression of core antigen, and production of virus particles was assessed by density-gradient centrifugation. Infectious virus was only observed in the culture medium of cells transfected with TFP1 HCV RNA. A chimeric genome with the structural segment (5'-untranslated region [UTR] through NS2) from sAH and the replication machinery (NS3 through 3' UTR) from TPF1 exhibited greater infectivity than did TFP1, despite formation of deficient virus particles in sAH, suggesting that this genomic segment potentiates virus particle formation. To identify the responsible variants, infectious virus formation was assessed in a chimeric genome carrying parts of the sAH structural segment of the TPF1 genome. A variant in NS2 (M170T) was identified that enhanced infectious virus formation. HCVcc carrying an NS2 gene encoding the M170T substitution and adaptive mutations in NS4B (referred to as TPF1-M170T) infected naive cured Huh7 cells in a CD81-dependent manner. CONCLUSIONS: We established a novel HCVcc of genotype 1b in Huh7 cells by introducing an amino acid variant in NS2 and adaptive mutations in NS4B from HCV genomic RNA isolated from a patient with fulminant HCV after liver transplantation. PMID- 27678342 TI - The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis. AB - BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI 4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 27678343 TI - Quantitative PCR for HTLV-1 provirus in adult T-cell leukemia/lymphoma using paraffin tumor sections. AB - Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers. The results were analyzed with a simple regression model and a novel criterion, cut-off using 95 % rejection limits. Our quantitative PCR assay showed an excellent association between tumor ratios and the copy numbers (r = 0.89, P < 0.0001). The 95 % rejection limits provided a statistical basis for the range for the determination of HTLV-1 involvement. Its application suggested that results of non-quantitative PCR assay should be interpreted very carefully and that our quantitative PCR assay is useful to estimate the status of HTLV-1 involvement in the tumor cases. In conclusion, our quantitative PCR assay using paraffin tumor sections may be useful for the screening of ATLL cases, especially in HTLV-1 non-endemic areas where easy access to serological testing for HTLV-1 infection is limited. PMID- 27678344 TI - Pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. AB - BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system able to induce regression of peritoneal metastasis (PM) in the salvage situation. The aim of this study was to determine the clinical characteristics, tumor histology, and extent of disease of the patients having undergone cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after "neoadjuvant" PIPAC. METHODS: This study was performed at a single institution, tertiary center. In a prospective registry, retrospective analysis was done. PIPAC indication was restricted to patients in the salvage situation who were not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). RESULTS: Nine-hundred sixty one PIPAC sessions were successfully performed in 406 patients: 21 patients (5.2 %) were scheduled for CRS and HIPEC. Twelve of these patients had a low PCI (mean 5.8 +/- 5.6). The remaining nine patients showed an advanced peritoneal disease (mean PCI 14.3 +/- 5.3) at initial laparoscopy. After repeated PIPAC (mean number of cycles 3.5 +/- 0.9), radiological tumor regression was observed in 7/9 patients and major histological regression was observed in 8/9 patients, so that secondary CRS and HIPEC became possible. CONCLUSIONS: PIPAC might be used as a neoadjuvant therapy before CRS and HIPEC in order to improve the outcome of CRS and HIPEC, to select patients with chemosensitive, biologically favorable tumors, to extent the indications of CRS and HIPEC in the presence of diffuse small bowel involvement, and to reduce the extent of cytoreductive surgery. PMID- 27678345 TI - C reactive protein and depressive symptoms in hemodialysis patients: A questionable association. AB - INTRODUCTION: Patients with advanced chronic kidney disease (CKD) on haemodialysis (HD) may have increased C reactive protein (CRP) values and depressive symptoms. There is debate about the strength and nature of previously reported associations. We investigated these issues in a cohort of patients on HD. METHODS: We screened for depressive symptoms using two valadiated depression screening tools: the Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire (PHQ-9). Demographic and clinical correlates of depression symptoms were eveluated in adjusted linear and logistic regression models, which included extra renal comorbidity and high CRP (>5 mg/L). FINDINGS: Three hundred and ninety-six HD patients were studied; 63.1% male, mean age 63.1 +/- 16.4 years, median CRP 6 (5-15) mg/L. Depression scores were similar in those with normal and high CRP (BDI-II (9(5-17) vs. 11(6-20)) or PHQ (4(2-9) vs. 6(2-10)). In adjusted multivariable regression BDI-II scores were associated with previous history of depression (beta 10.8, P < 0.001), serum albumin (beta 0.41, P < 0.001), anuria (beta 2.4, P < 0.037), diabetes (beta 2.7, P = 0.033), and age (beta -0.10, P = 0.009). High CRP was not independently associated with BDI-II (beta 2.20, P = 0.057), though was with PHQ-9 (beta 1.20, P = 0.046). In logistic regression those with high CRP were 1.9 times more likely to score >=16 on BDI-II screening (P = 0.016), but did not relate significantly to a PHQ-score >=10. DISCUSSION: A relationship was observed between CRP and depression symptoms, though the effect was small, of unlikely clinical significance, and inconsistent between depression measures. Previous reports of this association may reflect overlap between symptoms of depression and advanced CKD. PMID- 27678346 TI - Shared and Distinct Patterns of Oligodendroglial Response in alpha Synucleinopathies and Tauopathies. AB - Pathological protein deposits in oligodendroglia are common but variable features of various neurodegenerative conditions. To evaluate oligodendrocyte response in neurodegenerative diseases (NDDs) with different extents of oligodendroglial protein deposition we performed immunostaining for tubulin polymerization promoting protein p25alpha (TPPP/p25alpha), alpha-synuclein (alpha-syn), phospho tau, ubiquitin, myelin basic protein, and the microglial marker HLA-DR. We investigated cases of multiple system atrophy ([MSA] n = 10), Lewy body disease ([LBD] n = 10), globular glial tauopathy ([GGT] n = 7) and progressive supranuclear palsy ([PSP] n = 10). Loss of nuclear TPPP/p25alpha immunoreactivity correlated significantly with the degree of microglial reaction and loss of myelin basic prtein density as a marker of tract degeneration. This was more prominent in MSA and GGT, which, together with enlarged cytoplasmic TPPP/p25alpha immunoreactivity and inclusion burden allowed these disorders to be grouped as predominant oligodendroglial proteinopathies. However, distinct features, ie more colocalization of alpha-syn than tau with TPPP/p25alpha, more obvious loss of oligodendrocyte density in MSA, but more prominent association of tau protein inclusions in GGT to loss of nuclear TPPP/p25alpha immunoreactivity, were also recognized. In addition, we observed previously underappreciated oligodendroglial alpha-synuclein pathology in the pallidothalamic tract in LBD. Our study demonstrates common and distinct aspects of oligodendroglial involvement in the pathogenesis of diverse NDDs. PMID- 27678347 TI - Preventive health measures in inflammatory bowel disease. AB - We aim to review the literature and provide guidance on preventive health measures in inflammatory bowel disease (IBD). Structured searches were performed in PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library from January 1976 to June 2016 using the following keywords: (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (health maintenance OR preventive health OR health promotion). Abstracts of the articles selected from each of these multiple searches were reviewed, and those meeting the inclusion criteria (that is, providing data regarding preventive health or health maintenance in IBD patients) were recorded. Reference lists from the selected articles were manually reviewed to identify further relevant studies. Patients with IBD are at increased risk of developing adverse events related to the disease course, therapeutic interventions, or non-adherence to medication. Recent studies have suggested that IBD patients do not receive preventive services with the same thoroughness as patients with other chronic diseases. Preventive health measures can avert morbidity and improve the quality of life of patients with IBD. Gastroenterologists and primary care physicians (PCPs) should have an up to date working knowledge of preventive health measures for IBD patients. A holistic approach and better communication between gastroenterologists and PCPs with explicit clarification of roles will prevent duplication of services and streamline care. PMID- 27678348 TI - Challenges of advanced hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID- 27678349 TI - Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease. AB - After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula. PMID- 27678350 TI - Tolerance in liver transplantation: Biomarkers and clinical relevance. AB - Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as "operational tolerance". However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio. PMID- 27678352 TI - Management of patients after recovering from acute severe biliary pancreatitis. AB - Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature. PMID- 27678353 TI - Recent advances in orally administered cell-specific nanotherapeutics for inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a chronic relapsing disease in gastrointestinal tract. Conventional medications lack the efficacy to offer complete remission in IBD therapy, and usually associate with serious side effects. Recent studies indicated that nanoparticle-based nanotherapeutics may offer precise and safe alternative to conventional medications via enhanced targeting, sustained drug release, and decreased adverse effects. Here, we reviewed orally cell-specific nanotherapeutics developed in recent years. In addition, the various obstacles for oral drug delivery are also reviewed in this manuscript. Orally administrated cell-specific nanotherapeutics is expected to become a novel therapeutic approach for IBD treatment. PMID- 27678354 TI - Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article. AB - Emerging data have highlighted the co-existence of non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease, largely due to differences in disease definition and diagnostic tools utilised in the studies. Age, obesity, insulin resistance and other metabolic conditions are common risks factors in observational studies. However, other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity, duration, steroid use and prior surgical intervention, in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability, gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity, however no definitive evidence exist linking them to the development of hepatic steatosis, nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification, intervention and improve patient outcomes. PMID- 27678351 TI - Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum. AB - Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Besides the lymphatic and haematogenous routes of dissemination, CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity, which ultimately leads to peritoneal carcinomatosis (PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However, this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements, involving several well-defined steps, together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor, gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum, subsequently invade the subperitoneal space, where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript, we review current data regarding the molecular mechanisms underlying the development of colorectal PC, with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread. PMID- 27678356 TI - Spontaneous fungal peritonitis: Epidemiology, current evidence and future prospective. AB - Spontaneous bacterial peritonitis is a complication of ascitic patients with end stage liver disease (ESLD); spontaneous fungal peritonitis (SFP) is a complication of ESLD less known and described. ESLD is associated to immunodepression and the resulting increased susceptibility to infections. Recent perspectives of the management of the critically ill patient with ESLD do not specify the rate of isolation of fungi in critically ill patients, not even the antifungals used for the prophylaxis, neither optimal treatment. We reviewed, in order to focus the epidemiology, characteristics, and, considering the high mortality rate of SFP, the use of optimal empirical antifungal therapy the current literature. PMID- 27678355 TI - Inflammatory bowel disease and airway diseases. AB - Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact. PMID- 27678357 TI - Seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up. AB - Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world. PMID- 27678358 TI - Sessile serrated adenoma/polyps: Where are we at in 2016? AB - It is currently known that colorectal cancers (CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway (50%-70%); the mutator "Lynch syndrome" route (3%-5%); and the serrated pathway (30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA), the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders, submucosal injection of a dye solution (for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions. PMID- 27678360 TI - Tumor necrosis factor-alpha -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients. AB - AIM: To investigate the association of tumor necrosis factor alpha (TNFalpha) G308A polymorphism with different liver pathological changes in treatment-naive Egyptian patients infected with hepatitis C virus (HCV) genotype 4. METHODS: This study included 180 subjects, composed of 120 treatment-naive chronic HCV patients with different fibrosis grades (F0-F4) and 60 healthy controls. The TNFalpha G308A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFalpha protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFalpha -G308A genotypes on TNFalpha expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence. RESULTS: Current data showed that the TNFalpha -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients (F2-F4, n = 60) than in early fibrosis patients (F0-F1, n = 60) (P = 0.05, 0.04 respectively). Moreover, the GA or AA genotypes increased the TNFalpha serum level greater than the GG genotype (P = 0.002). The results showed a clear association between severe liver pathological conditions (inflammation, steatosis and fibrosis) and (GA + AA) genotypes (P = 0.035, 0.03, 0.04 respectively). The stepwise logistic regression analysis showed that the TNFalpha genotypes (GA + AA) were significantly associated with liver inflammation (OR = 3.776, 95%CI: 1.399-10.194, P = 0.009), severe steatosis (OR = 4.49, 95%CI: 1.441-14.0, P = 0.010) and fibrosis progression (OR = 2.84, 95%CI: 1.080-7.472, P = 0.034). Also, the A allele was an independent risk factor for liver inflammation (P = 0.003), steatosis (P = 0.003) and fibrosis (P = 0.014). CONCLUSION: TNFalpha SNP at nucleotide -308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected patients. PMID- 27678359 TI - Long-term outcomes of autoimmune pancreatitis. AB - Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID- 27678361 TI - Effects of Lizhong Tang on gastrointestinal motility in mice. AB - AIM: To investigate the effects of Lizhong Tang, a traditional Chinese medicine formula, on gastrointestinal motility in mice. METHODS: The in vivo effects of Lizhong Tang on GI motility were investigated by measuring the intestinal transit rates (ITRs) and gastric emptying (GE) values in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). RESULTS: In normal ICR mice, the ITR and GE values were significantly and dose-dependently increased by Lizhong Tang (ITR values: 54.4% +/- 1.9% vs 65.2% +/- 1.8%, P < 0.01 with 0.1 g/kg Lizhong Tang and 54.4% +/- 1.9% vs 83.8% +/- 1.9%, P < 0.01 with 1 g/kg Lizhong Tang; GE values: 60.7% +/- 1.9% vs 66.8% +/- 2.1%, P < 0.05 with 0.1 g/kg Lizhong Tang and 60.7% +/- 1.9% vs 72.5% +/- 1.7%, P < 0.01 with 1 g/kg Lizhong Tang). The ITRs of the GMD mice were significantly reduced compared with those of the normal mice, which were significantly and dose-dependently reversed by Lizhong Tang. Additionally, in loperamide- and cisplatin-induced models of GE delay, Lizhong Tang administration reversed the GE deficits. CONCLUSION: These results suggest that Lizhong Tang may be a novel candidate for development as a prokinetic treatment for the GI tract. PMID- 27678362 TI - (18)F-fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma. AB - AIM: To compare (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma. METHODS: Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent (18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions, including FDG avidity, pattern (focal/diffuse), and intensity [maximal standard uptake value: (SUVmax)]. The correlation of SUVmax with gastric clinicopathological variables was investigated by chi(2) test, and receiver-operating characteristic (ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS: Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients (94.23%) with gastric lymphoma and 65 patients (89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type I and type II lesions, whereas gastric carcinoma patients mainly had type III lesions. The SUVmax (13.39 +/- 9.24 vs 8.35 +/- 5.80, P < 0.001) and SUVmax/THKmax (maximal thickness) (7.96 +/- 4.02 vs 4.88 +/- 3.32, P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone. CONCLUSION: PET/CT features differ between gastric lymphoma and carcinoma, which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma. PMID- 27678364 TI - Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area. AB - AIM: To determine the role of screening and surveillance of hepatocellular carcinoma (HCC) in treatment-naive chronic hepatitis B (CHB) patients. METHODS: We recruited 2293 CHB patients (both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography (AUS) and serum alpha-fetoprotein (AFP) assay every 6 mo. The diagnosis, staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score < 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis. RESULTS: Among 2293 treatment naive CHB patients, seven cases had HCC at initial screening, giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis, all of which were Child-Pugh class A. With a median follow-up time of 42 (range, 3-48) mo, 10 additional cases were diagnosed with HCC, resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged >= 40 years. Most were at an early stage (Stage 0, A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation, with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis, increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels >= 20 MUg/L at diagnosis were observed in only 7/17 patients, most with a tumor size > 5 cm. For HCC screening and surveillance, AUS had a sensitivity and specificity of 94% and 82%, respectively, whereas the sensitivity and specificity of AFP at a cut-off value of >= 20 MUg/L were 41% and 98%, respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION: Implementation of active screening and surveillance using AUS to detect early-stage HCC in naive CHB patients aged >= 40 years in an endemic area is of benefit. PMID- 27678363 TI - Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy. AB - AIM: To analyze the risk factors for pancreatic fistula after pancreaticoduodenectomy. METHODS: We conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed at our hospital from March 2012 to October 2015. Pancreatic fistula was diagnosed in strict accordance with the definition of pancreatic fistula from the International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis. RESULTS: A total of 269 (49.9%) cases of pancreatic fistula occurred after pancreaticoduodenectomy, including 71 (13.17%) cases of grade A pancreatic fistula, 178 (33.02%) cases of grade B, and 20 (3.71%) cases of grade C. Univariate analysis showed no significant correlation between postoperative pancreatic fistula (POPF) and the following factors: age, hypertension, alcohol consumption, smoking, history of upper abdominal surgery, preoperative jaundice management, preoperative bilirubin, preoperative albumin, pancreatic duct drainage, intraoperative blood loss, operative time, intraoperative blood transfusion, Braun anastomosis, and pancreaticoduodenectomy (with or without pylorus preservation). Conversely, a significant correlation was observed between POPF and the following factors: gender (male vs female: 54.23% vs 42.35%, P = 0.008), diabetes (non-diabetic vs diabetic: 51.61% vs 39.19%, P = 0.047), body mass index (BMI) (<= 25 vs > 25: 46.94% vs 57.82%, P = 0.024), blood glucose level (<= 6.0 mmol/L vs > 6.0 mmol/L: 54.75% vs 41.14%, P = 0.002), pancreaticojejunal anastomosis technique (pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single layer mucosa-to-mucosa anastomosis: 57.54% vs 35.46%, P = 0.000), diameter of the pancreatic duct (<= 3 mm vs > 3 mm: 57.81% vs 38.36%, P = 0.000), and pancreatic texture (soft vs hard: 56.72% vs 29.93%, P = 0.000). Multivariate logistic regression analysis showed that gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter <= 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy. CONCLUSION: Gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter <= 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy. PMID- 27678365 TI - Cost effectiveness of routine duodenal biopsies in iron deficiency anemia. AB - AIM: To investigate the cost effectiveness of routine small bowel biopsies (SBBs) in patients with iron deficiency anemia (IDA) independent of their celiac disease (CD) serology test results. METHODS: We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy (EGD) in all patients with IDA regardless their celiac serology status (strategy A) vs SBBs only in IDA patients with positive serology (strategy B). The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results, a Monte Carlo simulation of 100 sample trials with 10, and an acceptability curve were performed. RESULTS: Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness, strategy A was the dominant strategy, as long as the cost of SBBs stayed less than $67. In addition, the ICER of strategy A was preferable, providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION: Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA, regardless of their celiac antibody status. PMID- 27678366 TI - Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. AB - AIM: To review Hepatitis C virus (HCV) prevalence and genotypes distribution worldwide. METHODS: We conducted a systematic study which represents one of the most comprehensive effort to quantify global HCV epidemiology, using the best available published data between 2000 and 2015 from 138 countries (about 90% of the global population), grouped in 20 geographical areas (with the exclusion of Oceania), as defined by the Global Burden of Diseases project (GBD). Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions, although their populations were included in the total population size of each region when generating regional genotype prevalence estimates. RESULTS: Total global HCV prevalence is estimated at 2.5% (177.5 million of HCV infected adults), ranging from 2.9% in Africa and 1.3% in Americas, with a global viraemic rate of 67% (118.9 million of HCV RNA positive cases), varying from 64.4% in Asia to 74.8% in Australasia. HCV genotype 1 is the most prevalent worldwide (49.1%), followed by genotype 3 (17.9%), 4 (16.8%) and 2 (11.0%). Genotypes 5 and 6 are responsible for the remaining < 5%. While genotypes 1 and 3 are common worldwide, the largest proportion of genotypes 4 and 5 is in lower-income countries. Although HCV genotypes 1 and 3 infections are the most prevalent globally (67.0% if considered together), other genotypes are found more commonly in lower-income countries where still account for a significant proportion of HCV cases. CONCLUSION: A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments. PMID- 27678367 TI - Double-layered covered stent for the treatment of malignant oesophageal obstructions: Systematic review and meta-analysis. AB - AIM: To investigate the efficacy of double-layered covered stent in the treatment of malignant oesophageal obstructions. METHODS: A systematic review and meta analysis was performed following the PRISMA process. PubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus and online content, were searched for studies reporting on the NiTi-S polyurethane-covered double oesophageal stent for the treatment of malignant dysphagia. Weighted pooled outcomes were synthesized with a random effects model to account for clinical heterogeneity. All studies reporting the outcome of palliative management of dysphagia due to histologically confirmed malignant oesophageal obstruction using double-layered covered nitinol stent were included. The level of statistical significance was set at alpha = 0.05. RESULTS: Six clinical studies comprising 250 patients in total were identified. Pooled technical success of stent insertion was 97.2% (95%CI: 94.8%-98.9%; I (2) = 5.8%). Pooled complication rate was 27.6% (95%CI: 20.7%-35.2%; I (2) = 41.9%). Weighted improvement of dysphagia on a scale of 0-5 scoring system was -2.00 [95%CI: -2.29%-(-1.72%); I (2) = 87%]. Distal stent migration was documented in 10 out of the 250 cases examined. Pooled stent migration rate was 4.7% (95%CI: 2.5%-7.7%; I (2) = 0%). Finally, tumour overgrowth was reported in 34 out of the 250 cases with pooled rate of tumour overgrowth of 11.2% (95%CI: 3.7%-22.1%; I (2) = 82.2%). No funnel plot asymmetry to suggest publication bias (bias = 0.39, P = 0.78). In the sensitivity analysis all results were largely similar between the fixed and random effects models. CONCLUSION: The double-layered nitinol stent provides immediate relief of malignant dysphagia with low rates of stent migration and tumour overgrowth. PMID- 27678368 TI - Immunohistochemical evaluation for outflow reconstruction using opened round ligament in living donor right posterior sector graft liver transplantation: A case report. AB - Utilizing the opened round ligament as venous grafts during liver transplantation is useful but controversial, and there are no pathological analyses of this procedure. Herein, we describe the first reported case of a pathological analysis of an opened round ligament used as a venous patch graft in a living donor liver transplantation (LDLT). A 13-year-old female patient with biliary atresia underwent LDLT using a posterior segment graft from her mother. The graft had two hepatic veins (HVs), which included the right HV (RHV; 15 mm) and the inferior RHV (IRHV; 20 mm). The graft RHV and IRHV were formed into a single orifice using the donor's opened round ligament (60 mm * 20 mm) as a patch graft during bench surgery; it was then anastomosed end-to-side with the recipient inferior vena cava. The recipient had no post-transplant complications involving the HVs, but she died of septic shock with persistent cholangitis and jaundice 86 d after LDLT. The HV anastomotic site had no stenosis or thrombus on autopsy. On pathology, there was adequate patency and continuity between the recipient's HV and the donor's opened round ligament. In addition, the stains for CD31 and CD34 on the inner membrane of the opened round ligament were positive. Hepatic venous reconstruction using the opened round ligament as a venous patch graft is effective in LDLT, as observed on pathology. PMID- 27678369 TI - Upregulation of MiR-196a promotes cell proliferation by downregulating p27kip1 in laryngeal cancer. AB - BACKGROUND: Accumulating evidence has confirmed that miR-196a plays a critical role in tumorigenesis and tumor progression in a variety of cancers. It has been demonstrated that miR-196a is highly up-regulated in laryngeal cancer by miRNA profiling analysis. However, the functional mechanism of miR-196a in laryngeal cancer remains unclear. This study aims to explore the mechanism of miR-196a in laryngeal cancer. METHODS: In the present study, we conducted qPCR analysis of miR-196a expression in human laryngeal cancer and showed that miR-196a was overexpressed in tumor-derived samples and laryngeal cancer cell lines compared with matched normal controls. Further functional analysis of miR-196a demonstrated that the inhibition of miR-196a could inhibit laryngeal cell-cycle progression and proliferation in vitro. Luciferase reporter assay and western blot confirmed that miR-196a directly targeted p27kip1. Moreover, in order to investigate whether miR-196a regulated cell growth in laryngeal cancer cells by targeting p27kip1, rescue studies were performed in laryngeal cancer cells. RESULTS: Results showed that overexpression of p27kip1 rescue decreased cell proliferation caused by miR-196a inhibitors. A negative relation between miR-196a and p27kip1 expression in laryngeal cancer tissues were also noted by further analyses. CONCLUSIONS: The present study showed that miR-196a was upregulated in laryngeal cancer and promoted cell proliferation by downregulating p27kip1 in laryngeal cancer. However, further studies are needed to verify this finding. PMID- 27678370 TI - Economic evaluation of trimetazidine in the management of chronic stable angina in Greece. AB - BACKGROUND: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b blockers, nitrates or calcium channel antagonists in Greece. METHODS: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective. The clinical inputs and utility values were extracted from the published literature. Resource consumption data were obtained from local experts, using a questionnaire developed for the purpose of the study and were combined with unit cost data (in ?2016) obtained from official sources. Cost effectiveness was assessed by calculating the incremental cost effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) was performed to account for uncertainty and variation in the input parameters of the model. RESULTS: The analysis showed that the cost of TMZ plus SoC was ?1755.57 versus ?1751.76 of SoC alone. In terms of health outcomes, TMZ plus SoC was associated with 0.6650 QALYs versus 0.6562 QALYs for SoC alone. The incremental analysis resulted in an ICER of ?430.67 per QALY gained. PSA revealed that the probability of TMZ plus SoC being cost-effective over SoC was 89 %, at a threshold of ?34,000 per QALY gained. CONCLUSION: The results indicate that TMZ as add -on treatment may be a highly cost-effective option for the symptomatic treatment of patients with chronic stable angina in Greece relative to SoC alone. PMID- 27678371 TI - Profiling of core fucosylated N-glycans using a novel bacterial lectin that specifically recognizes alpha1,6 fucosylated chitobiose. AB - A novel fucose-binding lectin (SL2-1) from the bacterium Streptomyces rapamycinicus was identified by analysis of metagenomic DNA sequences. SL2-1 belongs to a new group of bacterial fucose-specific lectins that have no similarity to known bacterial fucose-binding proteins, but are related to certain eukaryotic fucose-binding lectins. The 17 kDa protein was expressed recombinantly in E. coli and purified by affinity chromatography. Glycan microarray analysis with fluorescently labeled recombinant SL2-1 demonstrated its ability to bind to core alpha1-6 fucosylated N-glycans, but not to core alpha1-3 fucosylated N glycans, or other alpha1-2, alpha1-3 and alpha1-4 fucosylated oligosaccharides. The minimal high affinity binding epitope of SL2-1 was alpha1-6 fucosylated di-n acetylchitobiose. The recombinant lectin was efficient in detection of N-glycan core fucosylation using lectin blotting and lectin ELISA assays. Finally, a workflow using SL2-1 for selective and quantitative profiling of core fucosylated N-glycans using UPLC-HILIC-FLR analysis was established. The approach was validated for selective capture and analysis of core fucosylated N-glycans present in complex glycan mixtures derived from mammalian serum IgG. PMID- 27678372 TI - The novel thiosemicarbazone, di-2-pyridylketone 4-cyclohexyl-4-methyl-3 thiosemicarbazone (DpC), inhibits neuroblastoma growth in vitro and in vivo via multiple mechanisms. AB - BACKGROUND: Neuroblastoma is a relatively common and highly belligerent childhood tumor with poor prognosis by current therapeutic approaches. A novel anti-cancer agent of the di-2-pyridylketone thiosemicarbazone series, namely di-2 pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), demonstrates promising anti-tumor activity. Recently, a second-generation analogue, namely di-2 pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), has entered multi center clinical trials for the treatment of advanced and resistant tumors. The current aim was to examine if these novel agents were effective against aggressive neuroblastoma in vitro and in vivo and to assess their mechanism of action. METHODS: Neuroblastoma cancer cells as well as immortalized normal cells were used to assess the efficacy and selectivity of DpC in vitro. An orthotopic SK-N-LP/Luciferase xenograft model was used in nude mice to assess the efficacy of DpC in vivo. Apoptosis in tumors was confirmed by Annexin V/PI flow cytometry and H&E staining. RESULTS: DpC demonstrated more potent cytotoxicity than Dp44mT against neuroblastoma cells in a dose- and time-dependent manner. DpC significantly increased levels of phosphorylated JNK, neuroglobin, cytoglobin, and cleaved caspase 3 and 9, while decreasing IkBalpha levels in vitro. The contribution of JNK, NF-KB, and caspase signaling/activity to the anti-tumor activity of DpC was verified by selective inhibitors of these pathways. After 3 weeks of treatment, tumor growth in mice was significantly (p < 0.05) reduced by DpC (4 mg/kg/day) given intravenously and the agent was well tolerated. Xenograft tissues showed significantly higher expression of neuroglobin, cytoglobin, caspase 3, and tumor necrosis factor-alpha (TNFalpha) levels and a slight decrease in interleukin-10 (IL-10). CONCLUSIONS: DpC was found to be highly potent against neuroblastoma, demonstrating its potential as a novel therapeutic for this disease. The ability of DpC to increase TNFalpha in tumors could also promote the endogenous immune response to mediate enhanced cancer cell apoptosis. PMID- 27678373 TI - Glaucoma following phakic posterior chamber intraocular lens implantation. PMID- 27678374 TI - Role of Landlords in Creating Healthy Homes: Section 8 Landlord Perspectives on Healthy Housing Practices. AB - PURPOSE: This article presents qualitative research findings of Section 8 landlord perceptions regarding healthy housing practices to inform landlord focused initiatives. Approach or Design: Five focus groups were conducted with landlords. SETTING: Boston, Massachusetts. PARTICIPANTS: Section 8 landlords participated in focus groups (n = 39). METHOD: Focus group transcripts were coded for key themes using a grounded theory approach. RESULTS: Landlords' primary challenges to creating a healthy housing environment included tenant behavior, financial burden, and policy enforcement; tenant safety and cost savings were seen as primary benefits. CONCLUSION: Landlords play a critical role in implementing healthy housing practices. Several opportunities exist to reduce barriers and capitalize on perceived benefits of implementing these practices, including increasing access to educational and financial resources. PMID- 27678376 TI - Peripheral blood neutrophil extracellular trap production and degradation in chronic periodontitis. AB - AIMS: To investigate ex vivo peripheral neutrophil extracellular trap (NET) production and their subsequent degradation by plasma in chronic periodontitis patients, and periodontally and systemically healthy-matched controls. MATERIALS AND METHODS: Chronic periodontitis patient and control (n = 40 pairs) peripheral blood neutrophils (PBN) were stimulated for NET quantification. A subset of patients received non-surgical periodontal therapy (n = 19) and NETs were quantified 3 months later alongside controls. Blood plasma was collected from patients and controls to quantify plasma-induced NET degradation (n = 19 pairs). Subsequent experiments quantified plasma concentrations of DNase-1, immunoglobulin G (IgG), free light chains (FLCs), and cystatin C. RESULTS: No differences were observed in NET production between patients and controls. However, NET production decreased significantly in patients post-treatment. Plasma NET degradation was significantly lower in patients than controls, which may be due to significantly reduced DNase-1 levels as demonstrated, or potentially due to elevated IgG/FLC concentrations in patients. NET degradation post-periodontal treatment was comparable between patients and controls. CONCLUSIONS: NET production was comparable between patients and controls; however, non-surgical therapy causes attenuated NETs. NET degradation by plasma is impaired in untreated chronic periodontitis, potentially increasing the chronic NET burden, which may enhance antimicrobial function, or conversely, increase the risk of autoimmune/inflammatory responses. PMID- 27678375 TI - Genome-wide identification of Drosophila dorso-ventral enhancers by differential histone acetylation analysis. AB - BACKGROUND: Drosophila dorso-ventral (DV) patterning is one of the best understood regulatory networks to date, and illustrates the fundamental role of enhancers in controlling patterning, cell fate specification, and morphogenesis during development. Histone acetylation such as H3K27ac is an excellent marker for active enhancers, but it is challenging to obtain precise locations for enhancers as the highest levels of this modification flank the enhancer regions. How to best identify tissue-specific enhancers in a developmental system de novo with a minimal set of data is still unclear. RESULTS: Using DV patterning as a test system, we develop a simple and effective method to identify tissue-specific enhancers de novo. We sample a broad set of candidate enhancer regions using data on CREB-binding protein co-factor binding or ATAC-seq chromatin accessibility, and then identify those regions with significant differences in histone acetylation between tissues. This method identifies hundreds of novel DV enhancers and outperforms ChIP-seq data of relevant transcription factors when benchmarked with mRNA expression data and transgenic reporter assays. These DV enhancers allow the de novo discovery of the relevant transcription factor motifs involved in DV patterning and contain additional motifs that are evolutionarily conserved and for which the corresponding transcription factors are expressed in a DV-biased fashion. Finally, we identify novel target genes of the regulatory network, implicating morphogenesis genes as early targets of DV patterning. CONCLUSIONS: Taken together, our approach has expanded our knowledge of the DV patterning network even further and is a general method to identify enhancers in any developmental system, including mammalian development. PMID- 27678377 TI - 'Why can't I just not drink?' A qualitative study of adults' social experiences of stopping or reducing alcohol consumption. AB - INTRODUCTION AND AIMS: Alcohol is ingrained in Australian culture, playing an important role in many social occasions. This can make reducing or stopping alcohol consumption challenging, as one risks rejecting, not just a drink but also the valued social norms that drink represents. This study aimed to investigate the social experiences of adults who stop or reduce their alcohol consumption. DESIGN AND METHODS: Sixteen semi-structured interviews were conducted with people aged over 25 years who had stopped or significantly reduced their alcohol consumption for at least 3 months in the past year and were thematically analysed. RESULTS: Participants found themselves stigmatised for violating expectations around alcohol consumption when they tried to stop or reduce their own drinking. Although most were able to either conceal their change in alcohol consumption or present it so that it did not challenge norms around drinking, this approach was seen as a temporary measure and not one to employ with people with whom they socialised regularly. Instead, many participants sought to change their interactions with their social group to focus on activities with which alcohol consumption was not strongly associated. DISCUSSION AND CONCLUSIONS: Reducing or stopping alcohol consumption can have positive consequences for health, yet it can also raise social challenges that individuals need to negotiate in order to maintain their social well-being. This tension suggests a need for health promotion campaigns to address the social as well as health consequences of reducing alcohol consumption. [Bartram A, Eliott J, Crabb S. 'Why can't I just not drink?' A qualitative study of adults' social experiences of stopping or reducing alcohol consumption. Drug Alcohol Rev 2017;26:449-455]. PMID- 27678378 TI - Structural mapping in statistical word problems: A relational reasoning approach to Bayesian inference. AB - Presenting natural frequencies facilitates Bayesian inferences relative to using percentages. Nevertheless, many people, including highly educated and skilled reasoners, still fail to provide Bayesian responses to these computationally simple problems. We show that the complexity of relational reasoning (e.g., the structural mapping between the presented and requested relations) can help explain the remaining difficulties. With a non-Bayesian inference that required identical arithmetic but afforded a more direct structural mapping, performance was universally high. Furthermore, reducing the relational demands of the task through questions that directed reasoners to use the presented statistics, as compared with questions that prompted the representation of a second, similar sample, also significantly improved reasoning. Distinct error patterns were also observed between these presented- and similar-sample scenarios, which suggested differences in relational-reasoning strategies. On the other hand, while higher numeracy was associated with better Bayesian reasoning, higher-numerate reasoners were not immune to the relational complexity of the task. Together, these findings validate the relational-reasoning view of Bayesian problem solving and highlight the importance of considering not only the presented task structure, but also the complexity of the structural alignment between the presented and requested relations. PMID- 27678380 TI - Erratum to: Role of olanzapine in chemotherapy-induced nausea and vomiting on platinum-based chemotherapy patients: a randomized controlled study. PMID- 27678379 TI - Lost and stranded: the experience of younger adults with advanced cancer. AB - PURPOSE: There has been increased awareness recently of the unique medical and psychosocial needs of adolescents and young adults (AYAs) with cancer. However, the existing AYA literature is mainly focused on curative disease or survivorship rather than on advanced disease. Using qualitative methodology, we sought to understand the experience of younger adults with advanced cancer. METHODS: Participants were interviewed using open-ended, discovery-oriented interviews. Data was analyzed using thematic analysis. In total, ten English-speaking advanced cancer patients who were being treated at a comprehensive cancer center in Canada, were interviewed. Participants were between the ages of 18 and 35, and seven of them were female. RESULTS: The diagnosis of cancer was universally experienced as isolating and unexpected, with serious illness regarded as a problem of older individuals. The core challenge of living in the face of dying was felt to be constantly present yet typically unarticulated. Meaning-making tended to be constructed around future-oriented goals rather than upon the life that had been lived. Individuals felt forcefully removed from the stream of life, with a perceived interruption in the developmental tasks of establishing adult identity, becoming autonomous, and forming new relationships. All cited a need for young adult-specific services, yet none could describe specific services that would be beneficial. Many expressed reluctance to engage in individual psychotherapeutic treatment. CONCLUSIONS: Advanced cancer in younger adults was perceived by them as isolating and as interfering with age-appropriate developmental tasks. Creative and flexible psychosocial support programs are needed to engage this population with limited expected survival. PMID- 27678381 TI - Identification of At-Risk Youth by Suicide Screening in a Pediatric Emergency Department. AB - The pediatric emergency department (ED) is a critical location for the identification of children and adolescents at risk for suicide. Screening instruments that can be easily incorporated into clinical practice in EDs to identify and intervene with patients at increased suicide risk is a promising suicide prevention strategy and patient safety objective. This study is a retrospective review of the implementation of a brief suicide screen for pediatric psychiatric ED patients as standard of care. The Ask Suicide Screening Questions (ASQ) was implemented in an urban pediatric ED for patients with psychiatric presenting complaints. Nursing compliance rates, identification of at risk patients, and sensitivity for repeated ED visits were evaluated using medical records from 970 patients. The ASQ was implemented with a compliance rate of 79 %. Fifty-three percent of the patients who screened positive (237/448) did not present to the ED with suicide-related complaints. These identified patients were more likely to be male, African American, and have externalizing behavior diagnoses. The ASQ demonstrated a sensitivity of 93 % and specificity of 43 % to predict return ED visits with suicide-related presenting complaints within 6 months of the index visit. Brief suicide screening instruments can be incorporated into standard of care in pediatric ED settings. Such screens can identify patients who do not directly report suicide-related presenting complaints at triage and who may be at particular risk for future suicidal behavior. Results have the potential to inform suicide prevention strategies in pediatric EDs. PMID- 27678382 TI - Pre-existing donor-specific antibodies are detrimental to kidney allograft only when persistent after transplantation. AB - Donor-specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty-seven patients (15.5%) had pre-existing DSA detected the day of transplantation. After 5 years, the pre-existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years (P = 0.009), a history of previous transplantation (P = 0.039), the presence of class II DSA (P = 0.009), an MFI of preformed DSA >3500 (P < 0.001), and the presence of two or more DSA (P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation. PMID- 27678383 TI - The Abdominal Reapproximation Anchor Device. AB - INTRODUCTION: Achieving primary fascial closure after damage control laparostomy can be challenging. A number of devices are in use, with none having yet emerged as best practice. In July 2013, at Westmead Hospital, we started using the abdominal reapproximation anchor (ABRA; Canica Design, Almonte, Ontario, Canada) device. We report on our experience. METHODS: A retrospective review of medical records for patients who had open abdomens managed with the ABRA device between July to December 2013 was done. Data extracted included age, sex, body mass index (BMI), reason for the open abdomen, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of laparostomies prior to ABRA placement, duration of placement, device complications, length of hospital and intensive care unit (ICU) stay, and outcomes. RESULTS: Four cases of open abdomens managed using the ABRA device were identified, with 3 a consequence of intra-abdominal sepsis and 1 a consequence of penetrating trauma. Mean BMI was 33.5 kg/m2, APACHE II score was 14.5, duration with open abdomen prior to ABRA placement was 11.75 days, duration with ABRA in situ was 9 days, duration of hospital stay was 64.25 days, and ICU stay was 37.75 days. Three patients (75%) achieved fascial closure, and 1 achieved skin closure. No incidences of enterocutaneous fistulae occurred. CONCLUSION: The ABRA is a unique emerging alternative to aid in achieving fascial closure in patients managed with open abdomens. Our case series demonstrates that it can be used effectively in selected patients. Studies are needed to compare its efficacy with more traditional methods. PMID- 27678384 TI - Luminescent Dinuclear Bis-Cyclometalated Gold(III) Alkynyls and Their Solvent Dependent Morphologies through Supramolecular Self-Assembly. AB - A series of luminescent bis-cyclometalated gold(III) complexes containing bridging alkynyl ligands of different natures has been synthesised and characterised. The photophysical properties of the complexes have been investigated through electronic absorption spectroscopy and emission studies. The vibronic emission bands are found to originate from the triplet intraligand (IL) pi-pi* excited states of the bis-cyclometalating ligands with some mixing of 3 IL pi-pi* character of the alkynyl ligands. The electrochemical study of a nonsymmetric dinuclear complex shows two successive reduction processes originating from the reductions of the two different cyclometalating ligands. The complexes are found to undergo supramolecular self-assembly processes driven by pi-pi stacking and hydrophobic/hydrophilic interactions to give honeycomb nanostructures, as revealed from the SEM images. Solvent-dependent morphological transformations have also been observed, which have been studied by SEM and 1 H NMR spectroscopy. PMID- 27678385 TI - Subacute mechanical stenosis due to twisted saphenous vein graft identified by intravascular ultrasound. PMID- 27678386 TI - Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery. AB - Well-defined poly(ethylene glycol)-b-allyl functional polylactide-b-polylactides (PEG-APLA-PLAs) are synthesized through sequential ring-opening polymerization. PEG-APLA-PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core-shell interface cross-linked micelles (ICMs) by micellization and UV-initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological-mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug-ICM formulations possess slow and sustained drug release profiles under physiological-mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox-loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross-linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs. PMID- 27678388 TI - Efficacy of lycopene on modulation of renal antioxidant enzymes, ACE and ACE gene expression in hyperlipidaemic rats. AB - INTRODUCTION: We aimed to evaluate the efficacy of lycopene on renal tissue antioxidant enzymes and angiotensin converting enzyme (ACE) gene expression and serum activity in diet-induced hyperlipidaemia. METHODS: Thirty-two female Wistar albino rats (200-250 g weight), 5-6 months of age, were randomly selected and divided into four groups. Group I received normal diet; group II received 24 g high fat diet/100 g of daily diet; group III received 24 g high fat diet/100 g daily diet and 200 ml of lycopene extract (twice a week) for 8 weeks; and group IV received 200 ml oral lycopene extract twice a week for 8 weeks. RESULTS: A marked increase was observed in plasma urea and creatinine levels, serum C reactive protein, kidney weight, tissue renal malonyldialdehyde level, ACE gene expression and serum level, while a decrease catalase level among hyperlipidaemic rats was observed. Histologically, interstitial inflammation and proliferation was seen. Lycopene supplementation significantly decreased plasma urea and creatinine, serum ACE, renal tissue malonyldialdehyde level and C-reactive protein level, while it increased tissue antioxidant enzymes level and total protein. Tissue inflammation and proliferation was improved. CONCLUSIONS: This finding suggests that supplementation of lycopene is effective for renal antioxidant enzymes, ACE gene expression and ACE serum level in hyperlipidaemic rats. PMID- 27678389 TI - Volume regulatory hormones and plasma volume in pregnant women with sickle cell disorder. AB - BACKGROUND: Sickle cell disease (haemoglobin SS (HbSS)) mainly affects those of West African origin and is associated with hypervolaemia. Plasma volume rises by up to 50% in normal pregnancy but was previously found to be paradoxically contracted in late sickle cell pregnancy. The renin-angiotensin-aldosterone system is activated very early in human pregnancy to support the plasma volume expansion. We hypothesised that activation of the renin-angiotensin-aldosterone system would be blunted in pregnant women with sickle cell disease. MATERIALS AND METHODS: We measured plasma volume and concentrations of plasma renin, angiotensinogen, aldosterone and other volume-related hormones in a cross sectional study of pregnant and non-pregnant Nigerian women with HbSS or HbAA. RESULTS: Plasma volume was higher in non-pregnant HbSS than HbAA women, but had not risen by 16 weeks, unlike plasma volume in HbAA women. The concentration of plasma renin also rose significantly less by 16 weeks in HbSS; angiotensinogen and aldosterone concentrations increased. CONCLUSIONS: The lower plasma renin concentration at 16 weeks with HbSS could be either primary or secondary to vasoconstriction related to inadequate vasodilator activity. The contracted plasma volume might then stimulate aldosterone synthesis by non-angiotensin II dependent stimulation. Studies of vasodilators such as nitric oxide, vasodilator eicosanoids or the PlGF/VEGF/sFlT-1 axis in pregnant HbSS and HbAA women will test this hypothesis. PMID- 27678390 TI - Breast Cancer Screening Among Korean Americans: A Systematic Review. AB - Cancer is the leading cause of death for Korean Americans (KAs). Breast cancer (BC) is the most commonly occurring cancer among KA women, and its rate has been rapidly increasing. Low BC screening rates for KAs puts them at greater risk for late-stage breast cancer. We conducted a systematic review of the published literature on cancer screening among KAs, and identified 38 eligible studies. Despite significant increases in mammogram utilization over the past two decades, KAs have consistently lower rates of mammogram screening than other American populations. KA women also report lower rates of clinical breast examination and breast self-examination. Screening rates are higher among adults with higher socioeconomic status, greater acculturation to the United States, more cancer knowledge, higher perceived susceptibility to BC, more social support, and better access to health services. However, fear of finding something wrong, fear of embarrassment or lack of modesty, not knowing where to go for screening, believing that mammography is only necessary when symptoms are present, and perceived time and cost difficulties in accessing mammography were reported as barriers to mammogram screening. Coordinated efforts from clinicians, public health workers, KA cultural and religious organizations, and the broader breast cancer advocacy and awareness community are necessary for improving BC screening among KAs. PMID- 27678391 TI - Post-Sling Urinary Retention in Women. AB - As many as 80 % of all women who complain of urine leakage will be diagnosed with stress urinary incontinence (SUI). As the population ages and SUI becomes more widespread, it is imperative to understand how to manage potential complications of the therapies used to treat this condition. As the mid-urethral sling has become the "gold standard" of SUI treatment, it is important to be aware of post operative complications associated with this procedure. One significant complication of the MUS is subsequent urinary retention. In this review, we discuss the potential etiologies of post-sling urinary retention and outline the various modalities for achieving a timely and accurate diagnosis. We also emphasize the applications of various diagnostic tools, such as urodynamics, when evaluating patients with post-sling urinary retention. Lastly, various treatments for this complication are discussed. This chapter serves as a comprehensive overview of how to approach post-sling urinary retention, underlining the recent academic research contributions that have enhanced our understanding of how to manage this condition. PMID- 27678392 TI - Advancement of Sialyltransferase Inhibitors: Therapeutic Challenges and Opportunities. AB - Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well-established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles. This has important implications for inhibitor development, as STs also play significant roles in immune responses, inflammation, viral infection, and neurological disorders. Thus, the current goal in order to advance to the clinic is the development of subtype selective, cell-permeable and synthetically accessible, small-molecule ST inhibitors. Herein is a comprehensive review of the latest developments in ST inhibitors from design, Nature, and high-throughput screening, addressing both the challenges and opportunities in targeting cell surface sialylation. The review features an overview of the biological evaluation methods, computational and imaging tools, inhibitor molecular diversity, and selectivity toward ST subtypes, along with the emerging role of ST inhibitors as diagnostic tools for disease imaging. PMID- 27678393 TI - Liver fibrosis staging with diffusion-weighted imaging: a systematic review and meta-analysis. AB - PURPOSE: A meta-analysis was performed to assess the diagnostic performance of diffusion-weighted imaging (DWI) in liver fibrosis (LF) staging. METHODS: We conducted a comprehensive literature search to identify relevant articles. Diagnostic data were extracted for each METAVIR fibrosis stage (F0-F4). A bivariate binomial model was used to combine sensitivities and specificities. Summary receiver operating characteristics (SROC) curves were performed and areas under SROC curve (AUC) were calculated to indicate diagnostic accuracies. Subgroup analyses were performed between different study characteristics. RESULTS: Twelve studies met the inclusion criteria for LF >=F1, 16 for >=F2, 18 for >=F3, and 12 for F4. AUCs of DWI were 0.8554, 0.8770, 0.8836, and 0.8596 for >=F1, >=F2, >=F3, and F4, respectively. Subgroup analyses showed that for LF >=F2 and >=F3, maximal b values (b max) >= 800 s/mm2 performed significantly better than b max < 800 s/mm2. The diagnostic accuracies of 3.0 T and intravoxel incoherent motion (IVIM)-DWI were significantly higher than those of 1.5 T and conventional DWI for diagnosing liver cirrhosis (F4). CONCLUSIONS: DWI is a reliable noninvasive technique with good diagnostic accuracy for LF staging. Using b max >= 800 s/mm2, high-field strength (3.0 T) and IVIM-DWI can optimize the diagnostic performance of DWI. PMID- 27678394 TI - Immersive bilingualism reshapes the core of the brain. AB - Bilingualism has been shown to affect the structure of the brain, including cortical regions related to language. Less is known about subcortical structures, such as the basal ganglia, which underlie speech monitoring and language selection, processes that are crucial for bilinguals, as well as other linguistic functions, such as grammatical and phonological acquisition and processing. Simultaneous bilinguals have demonstrated significant reshaping of the basal ganglia and the thalamus compared to monolinguals. However, it is not clear whether these effects are due to learning of the second language (L2) at a very young age or simply due to continuous usage of two languages. Here, we show that bilingualism-induced subcortical effects are directly related to the amount of continuous L2 usage, or L2 immersion. We found significant subcortical reshaping in non-simultaneous (or sequential) bilinguals with extensive immersion in a bilingual environment, closely mirroring the recent findings in simultaneous bilinguals. Importantly, some of these effects were positively correlated to the amount of L2 immersion. Conversely, sequential bilinguals with comparable proficiency and age of acquisition (AoA) but limited immersion did not show similar effects. Our results provide structural evidence to suggestions that L2 acquisition continuously occurs in an immersive environment, and is expressed as dynamic reshaping of the core of the brain. These findings propose that second language learning in the brain is a dynamic procedure which depends on active and continuous L2 usage. PMID- 27678396 TI - Quantitative risk analysis of the novel H7N9 virus in environments associated with H9 avian influenza virus, Zhejiang province, China. AB - H9 avian influenza virus played a key role during generation of the novel H7N9 virus. A surveillance programme was conducted to assess the H9 virus in relation to the risk of H7N9 virus contamination in the environment. Risk of H7N9 virus contamination in the presence of H9 virus was higher than without (adjusted odds ratio 4.49, 95% confidence interval 3.79-5.31). Adjusted odds ratios of the H7N9 virus associated with co-presence of H9 virus and interacting factors were 4.93 (rural vs. urban area), 46.80 (live poultry markets vs. other premises), 6.86 (Huzhou vs. Hangzhou prefecture), 40.67 (year 2015 vs. 2013), and 9.63 (sewage from cleaning poultry vs. poultry faeces). Regular surveillance on gene variability of H7N9 and H9 viruses should be conducted and extra measures are needed to reduce co-circulation of H7N9 and H9 viruses in the environment. PMID- 27678395 TI - Anatomical and molecular characterization of dopamine D1 receptor-expressing neurons of the mouse CA1 dorsal hippocampus. AB - In the hippocampus, a functional role of dopamine D1 receptors (D1R) in synaptic plasticity and memory processes has been suggested by electrophysiological and pharmacological studies. However, comprehension of their function remains elusive due to the lack of knowledge on the precise localization of D1R expression among the diversity of interneuron populations. Using BAC transgenic mice expressing enhanced green fluorescent protein under the control of D1R promoter, we examined the molecular identity of D1R-containing neurons within the CA1 subfield of the dorsal hippocampus. In agreement with previous findings, our analysis revealed that these neurons are essentially GABAergic interneurons, which express several neurochemical markers, including calcium-binding proteins, neuropeptides, and receptors among others. Finally, by using different tools comprising cell type specific isolation of mRNAs bound to tagged-ribosomes, we provide solid data indicating that D1R is present in a large proportion of interneurons expressing dopamine D2 receptors. Altogether, our study indicates that D1Rs are expressed by different classes of interneurons in all layers examined and not by pyramidal cells, suggesting that CA1 D1R mostly acts via modulation of GABAergic interneurons. PMID- 27678397 TI - Budgerigars (Melopsittacus undulatus) do not hear infrasound: the audiogram from 8 Hz to 10 kHz. AB - The pure-tone thresholds of three budgerigars were determined from 8 Hz to 10 kHz. At a level of 60 dB sound pressure level (re 20 MUN/m2), their hearing range extends 6.6 octaves from 77 Hz to 7.6 kHz, with a best sensitivity of 1.1 dB at 3 kHz. Unlike pigeons and chickens, budgerigars do not have better low-frequency hearing than humans. This difference implies anatomical, physiological, and ecological differences between birds that hear infrasound (so far, pigeons and chickens) and those that do not (budgerigars). PMID- 27678399 TI - [Stapler operations of the anorectum : Indications, techniques and results]. PMID- 27678400 TI - [Operative therapy of external rectal prolapse with a stapler]. AB - External rectal prolapse is a rare condition, which is more common in old and multimorbid women. In recent years five surgical methods have become established from among the multitude of operative procedures which have been described. One of the most recent techniques is perineal stapled prolapse resection (PSP) which is described in this article. After complete eversion of the rectal prolapse it is resected into 2 halves using a linear cutter by incisions at 3 o'clock and 9 o'clock lithotomy positions, followed by stepwise resection with a curved cutter along the ventral and dorsal circumference. There is low evidence for the treatment of external rectal prolapse. For PSP only case series exist with results that are similar to those from other techniques; however, comparative studies are nearly completely lacking. The PSP is a relatively new surgical technique for the treatment of external rectal prolapse. It is a safe surgical procedure. Due to the lack of evidence it should remain reserved for old and/or multimorbid patients. PMID- 27678401 TI - [Hospital volume effects in surgical treatment of gastric cancer : Results of a prospective multicenter observational study]. AB - BACKGROUND: The impact of hospital and surgeon volume on the treatment outcome based on data obtained from cohort and register studies has been controversially discussed in the international literature. The results of large-scale prospective observational studies within the framework of clinical healthcare research may lead to relevant recommendations in this ongoing discussion. MATERIAL AND METHODS: Within the framework of the prospective multicenter German Gastric Cancer Study 2 (QCGC 2), from 1 January 2007 to 31 December 2009 a total of 2897 patients with the histological diagnosis of gastric cancer from 140 surgical departments were registered and analyzed. The departments were subdivided according to the number of cases into 4 volume groups: I) <5, II) 5-10, III) 11 20 and IV) >20 patients with surgical interventions per year. RESULTS: Overall 1163 patients (65.6 %) underwent surgical interventions in the departments of groups III and IV. Of the patients 521 (18 %) were scheduled for neoadjuvant treatment but with no significant differences among the various volume groups. In the departments of volume groups I and II subtotal gastric resection was performed significantly more often. Transthoracic extended surgical interventions in cases of a proximal tumor site were significantly more frequent in departments from volume group IV (p <0.001). The proportion of intraoperative fresh frozen sections correlated with the case volume: group I 23.2 % vs. group IV 61.2 %. Overall hospital mortality was 6.1 % and slightly higher in volume group I with 7.8 %. The median survival time and the 5-year survival rate showed no significant differences between the various volume groups independent of tumor stages. There was a tendency towards a longer median survival time in volume group IV only for proximal tumor sites, i.e. adenocarcinoma of the esophagogastric junction (AEG). Using Cox regression analysis hospital volume did not have an independent impact on long-term survival. CONCLUSION: Hospital volume effects could only be detected for the treatment of AEG. To improve oncological long-term outcome, centralization of treatment of proximal gastric cancer appears to be recommendable. PMID- 27678398 TI - Characterization of the recombination activities of the Entamoeba histolytica Rad51 recombinase. AB - The protozoan parasite responsible for human amoebiasis is Entamoeba histolytica. An important facet of the life cycle of E. histolytica involves the conversion of the mature trophozoite to a cyst. This transition is thought to involve homologous recombination (HR), which is dependent upon the Rad51 recombinase. Here, a biochemical characterization of highly purified ehRad51 protein is presented. The ehRad51 protein preferentially binds ssDNA, forms a presynaptic filament and possesses ATP hydrolysis activity that is stimulated by the presence of DNA. Evidence is provided that ehRad51 catalyzes robust DNA strand exchange over at least 5.4 kilobase pairs. Although the homologous DNA pairing activity of ehRad51 is weak, it is strongly enhanced by the presence of two HR accessory cofactors, calcium and Hop2-Mnd1. The biochemical system described herein was used to demonstrate the potential for targeting ehRad51 with two small molecule inhibitors of human RAD51. We show that 4,4'-diisothiocyanostilbene-2,2' disulfonic acid (DIDS) inhibited ehRad51 by interfering with DNA binding and attenuated encystation in Entamoeba invadens, while B02 had no effect on ehRad51 strand exchange activity. These results provide insight into the underlying mechanism of homology-directed DNA repair in E. histolytica. PMID- 27678403 TI - [Cues and pseudocues in surgical multiple choice questions from the German state examination]. AB - AIM: Multiple choice questions (MCQs) are the most common written test item in medical examinations. Writing MCQs is difficult and cues can decrease test validity. The aim of this article is to describe the prevalence and pattern of cues in surgical MCQs in the central German medical examination questions from 2000-2011. METHOD: All surgical questions were entered into a database. The questions were reviewed for cues and pseudocues independently by three students of different academic background and one clinical physician. RESULTS: Initially, 1014 questions were included, 22 questions were not rated uniformly by the reviewers and 3 questions were excluded because no consensus could be reached. Overall 15.2 % of the questions analyzed contained some type of cue or pseudocue. Of the total questions 0.2 % contained type A cues (i.e. disruption of grammatical flow), 6.5 % contained type B cues (i.e. heterogeneous length or differentiation), 4.0 % contained type C cues (two or more answers described closely related topics, serving to focus attention), 0.6 % contained type D convergence cues (i.e. answers with the most items in common with distractors are correct), 0.7 % contained type E verbal association cues (i.e. connection in the use of words leading to the correct answer) and 1.0 % contained type F cues (i.e. answers with absolute terms). Pseudocues were found in 3.7 % of the questions. DISCUSSION: The proportion of questions that contained cues or pseudocues should lead to further efforts to avoid such factors compromising test reliability by specific attention in the process of question design and review. CONCLUSION: Cues are still an important consideration in designing MCQs and are present in considerable numbers in medical state examination questions. Pseudocues should be explicitly avoided so as not to compromise validity and reliability. PMID- 27678402 TI - [Gastric stump carcinoma: frequency, treatment, complications and prognosis]. AB - BACKGROUND: Gastric stump carcinoma develops in the gastric remnant after partial gastrectomy. While the frequency of gastric cancer is declining, the incidence of gastric stump carcinoma has remained stable due to the long latency period. As the surgical treatment of gastric ulcers by partial gastrectomy has become much less important, more and more gastric stump carcinomas develop after oncological resection. AIM: This study compared the surgical therapy of gastric stump carcinoma with the therapy of primary gastric cancer. MATERIAL AND METHODS: From 2001 to 2014 a total of 24 patients were surgically treated for gastric stump carcinoma in the University Hospital of Heidelberg. In the same time 428 patients underwent resection due to primary gastric cancer. Both groups were analyzed and compared with a focus on preoperative therapy, intraoperative differences, complications and overall survival. RESULTS: Patients with gastric stump carcinoma were older at disease onset (68 years vs. 62 years, p = 0.003). Compared with primary gastric cancer, patients with gastric stump carcinoma were more often suspected of having lymph node (cN+) involvement (51.4 % vs. 41.7 %, p < 0.001) but neoadjuvant therapy was applied less often (48.7 % vs. 14.3 %, p < 0.01). For resection of gastric stump carcinoma, extended resections were more often necessary (54.5 % vs. 28.2 %, p < 0.001). There were no significant differences in mean overall survival between the two patient groups (64.4 months vs. 45.8 months, p = 0.34) CONCLUSION: Despite the differences described, the treatment of gastric stump carcinoma does not essentially differ from that of primary gastric cancer. Carcinomas of the gastric stump are more often locally advanced and in our opinion a neoadjuvant therapy should be applied analogue to gastric cancer even if evidence-based data on this point are limited. PMID- 27678404 TI - System maps for retention of small neutral compounds on a superficially porous particle column in reversed-phase liquid chromatography. AB - The system constants of the solvation parameter model are used to prepare system maps for the retention of small neutral molecules on the ocadecylsiloxane-bonded silica superficially porous particle stationary phase (Kinetex C18) for aqueous organic solvent mobile phases containing 10-70% (v/v) methanol or acetonitrile. A comparison of the system constants with eight commercially available octadecylsiloxane-bonded silica columns for the same separation conditions confirms that the general retention properties of Kinetex C-18 are similar to totally porous octadecylsiloxane-bonded silica stationary phases and that method transfer should be no more difficult than that usually observed when substituting one octadecylsiloxane-bonded silica column for another. PMID- 27678405 TI - Magnetization of 3-dimentional homochiral metal-organic frameworks for efficient and highly selective capture of phosphopeptides. AB - Enrichment of phosphopeptides based on various affinity probes prior to mass spectrometry detection is usually required due to the low abundance and low ionization efficiency of phosphopeptides. In this work, a 3-dimentional homochiral metal-organic frameworks (MOFs) was modified with magnetic nanoparticles using a facile method and then utilized for phosphopeptides capture with high efficiency and specificity. Based on magnetic solid phase extraction, a rapid and efficient method was developed and the whole enrichment procedure could be easily finished within 10min. Efficient and highly selective capture of phosphopeptides from tryptic digests and human serum was achieved. This affinity probe showed satisfactory reproducibility of the particle synthesis and could be recycled for at least seven times. With all the advantages mentioned above, this strategy is of great potential for routine application in phosphoproteomes. PMID- 27678406 TI - Molecularly imprinted polymer monolith containing magnetic nanoparticles for the stir-bar sorptive extraction of triazines from environmental soil samples. AB - In this work, novel molecularly imprinted stir-bars based upon the entrapment of modified magnetic nanoparticles within an imprinted polymer monolith is developed for stir-bar sorptive extraction (SBSE). Firstly, magnetic nanoparticles were surface modified with oleic acid followed by encapsulation inside a silica network. Then, vinyl-groups were grafted onto the particles surface for the subsequent copolymerization with the imprinting polymerization mixture using a glass vial insert as a mold. As a result, the obtained imprinted monolith presented magnetic properties allowing its use as magnetic stir-bar. Variables affecting both polymer morphology (i.e., amount of magnetic nanoparticles, polymerization time) and binding-elution conditions of target analytes (i.e., solvents, time) was carefully optimized. Optimum imprinted stir-bars were evaluated for the SBSE of triazines in soil sample extracts. Recoveries, at 16ngg 1 concentration level, ranged from 2.4 to 8.7% with relative standard deviations lower than 15% (n=3). Although low recoveries were obtained, the high selectivity provided by the new molecularly imprinted stir-bars allowed reaching detection limits below 7.5ngg-1 by liquid chromatography coupled to UV detection. PMID- 27678407 TI - Association Between Celiac Disease and Asthma. PMID- 27678408 TI - Exploring the theoretical basis and limitations of cryo-STEM tomography for thick biological specimens. AB - Scanning transmission electron microscope (STEM) imaging has recently been applied to the cryo-tomography of thick biological specimens. As previously shown for plastic sections, STEM has a number of advantages for cryo-imaging compared to conventional wide-field TEM imaging. STEM is insensitive to phase coherence and is therefore suitable for much thicker specimens than TEM. Imaging in focus, with a long depth of field, also circumvents the complications of an oscillatory contrast transfer function and missing information at low spatial frequencies. Moreover the image signal represents a quantitative measurement of the electron scattering pixel by pixel, so that absolute intensities can be interpreted in terms of material properties in the specimen. Resolution, however, is undoubtedly compromised for thick samples, especially in the regime of multiple elastic scattering. In this work we address the specific issues that arise in cryo tomography of thick biological specimens. We formulate an imaging model based on a Boltzmann transport equation, complemented by Monte Carlo simulations. Using these theoretical tools, we identify conditions for image acquisition that will be compatible with the basic presumption of tomographic reconstruction, i.e., that for a given composition the imaging signal varies monotonically with thickness. For optimal resolution, contrast, and signal strength, we propose to generalize the on-axis bright field detector to collect at angles well beyond the illumination cone. Our results justify the generation of 3D images for micron thicknesses and beyond. PMID- 27678409 TI - Response to Wagner et al.: phosphodiesterase-2-anti-adrenergic friend or hypertrophic foe in heart disease? PMID- 27678410 TI - Differential effects of the enantiomers of tamsulosin and tolterodine on P glycoprotein and cytochrome P450 3A4. AB - The pregnane X receptor (PXR) is a transcription factor regulating P-glycoprotein (P-gp; ABCB1)-mediated transport and cytochrome P450 3A4 (CYP3A4)-mediated metabolism of xenobiotics thereby affecting the pharmacokinetics of many drugs and potentially modulating clinical efficacy. Thus, pharmacokinetic drug-drug interactions can arise from PXR activation. Here, we examined whether the selective alpha1-adrenoreceptor blocker tamsulosin or the antagonist of muscarinic receptors tolterodine affect PXR-mediated regulation of CYP3A4 and of P-gp at the messenger RNA (mRNA) and protein level in an enantiomer-specific way. In addition, the effect of tamsulosin and tolterodine on P-gp activity was evaluated. We used quantitative real-time PCR, gene reporter assay, western blotting, rhodamine efflux assay, and calcein assay for determination of expression, activity, and inhibition of P-glycoprotein. The studied compounds significantly and concentration-dependently increased PXR activity in the ABCB1 driven luciferase-based reporter gene assay. We observed much stronger induction of ABCB1 mRNA by S-tamsulosin as compared to the R or racemic form. R or racemic form of tolterodine and R-tamsulosin concentration-dependently increased P-gp protein expression; the latter also enhanced P-gp efflux function in a rhodamine based efflux assay. R-tamsulosin and all forms of tolderodine slightly inhibited P-gp. The effect on CYP3A4 expression followed the same pattern but was much weaker. Taken together, tamsulosin and tolterodine are demonstrated to interfere with P-gp and CYP3A4 regulation in an enantiomer-specific way. PMID- 27678411 TI - Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients. AB - INTRODUCTION: Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients. METHODS: The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (beta-CTX) and safety parameters were assessed. RESULTS: The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum beta-CTX level decreased by 50% (P<0.05). No serious adverse event was found. CONCLUSION: No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V. PMID- 27678412 TI - Marriage Markets and Male Mating Effort: Violence and Crime Are Elevated Where Men Are Rare. AB - The negative social outcomes in populations with male-biased sex ratios are a growing concern. In general, the expectation is of heightened violence as a result of excess men engaging in antisocial behavior and crime, thereby threatening societal stability. While intuitive, these claims are largely unsupported in the literature. Using mating market theory as our guide, we examine indicators of male mating effort, including (1) violent competition between men (homicide, aggravated assault) and (2) indicators of uncommitted sexual behavior (rape, sex offenses, and prostitution). Our unit of analysis is U.S. county-level data. We find that counties with more men have lower rates of crime and violent behavior. Our findings challenge conventional claims of male excess leading to elevated levels of violence. Instead, in support of mating market predictions, we find that criminal and violent behavior related to male mating effort is least common in male-biased sex ratios. We discuss the implications of our findings for public policy regarding incarceration and criminal behavior. PMID- 27678413 TI - Prefrontal cortical GABAergic and NMDA glutamatergic regulation of delayed responding. AB - NMDA glutamatergic and GABAergic transmission have both been implicated in regulating working memory functions mediated by the prefrontal cortex (PFC), and perturbations in these neurotransmitter systems have been proposed to underlie deficits in these functions observed in schizophrenia. Here, we examined the consequence of disrupting GABAergic or NMDA glutamatergic transmission within the medial PFC of rats on a delayed-response paradigm with translational relevance to working memory tasks used with humans. The operant delayed non-match to position task consisted of a sample phase (one lever extended) and a choice phase wherein rats were required to choose the opposite lever, separated by a variable delay (1 24 s). In well-trained rats, inactivation of the PFC via infusions of GABA agonists baclofen/muscimol (100 ng each) induced delay-independent deficits. Reducing PFC GABA transmission with the GABA-A receptor antagonist bicuculline (12.5-50 ng) also caused delay-independent impairments and increased trial omissions and response latencies during the sample and end-of-delay phases. On the other hand, non-selective blockade of PFC NMDA receptors with MK-801 (3-6 MUg) disrupted performance, but these effects more closely resembled delay dependent impairments. However, selective blockade of GluN2B-containing NMDA receptors with Ro-25-6981 (2.5 MUg) did not affect any measures of performance. These results demonstrate that both intact PFC GABA and NMDA receptor signalling are integral for accurate delayed-responding, although they may differentially regulate encoding vs maintenance of information within working memory. Furthermore they suggest that perturbations of both of these neurochemical signals within the PFC may contribute differentially to impairments in working memory observed in schizophrenia. PMID- 27678414 TI - Lack of GSK3beta activation and modulation of synaptic plasticity by dopamine in 5-HT1A-receptor KO mice. AB - Psychiatric disorders are associated with excitation-inhibition (E-I) balance impairment in the prefrontal cortex. However, how the E-I balance is regulated is poorly known. The E-I balance of neuronal networks is linked to the action of numerous neuromodulators such as dopamine and 5-HT. We investigated the role of D2-receptors in tuning the E-I balance in a mouse model of anxiety, the 5-HT1A receptor KO mice. We focused on synaptic plasticity of excitation and inhibition on layer 5 pyramidal neurons. We show that D2-receptor activation decreases the excitation and favors HFS-induced LTD of excitatory synapses via the activation of GSK3beta. This effect is absent in 5-HT1A-receptor KO mice. Our data show that the fine control of excitatory transmission by GSK3beta requires recruitment of D2-receptors and depends on the presence of 5-HT1A-receptors. In psychiatric disorders in which the number of 5-HT1A-receptors decreased, therapies should reconsider how serotonin and dopamine receptors interact and control neuronal network activity. PMID- 27678416 TI - Salubrinal attenuates right ventricular hypertrophy and dysfunction in hypoxic pulmonary hypertension of rats. AB - The phosphorylation of eukaryotic translation initiation factor 2 alpha (p eIF2alpha) is essential for cell survival during hypoxia. The aim of this study was to investigate whether salubrinal, an inhibitor of p-eIF2alpha dephosphorylation could attenuate pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy in rats exposed to hypobaric hypoxia. PAH of rats was induced by hypobaric hypoxia. Salubrinal supplemented was randomized in either a prevention or a reversal protocol. At the end of the follow-up point, we measured echocardiography, hemodynamics, hematoxylin-eosin and Masson's trichrome stainings. RNA-seq analysis is explored to identify changes in gene expression associated with hypobaric hypoxia with or without salubrinal. Compared with vehicle-treatment rats exposed to hypobaric hypoxia, salubrinal prevented and partly reversed the increase of the mean pulmonary artery pressure and RV hypertrophy. What's more, salubrinal reduced the percentage wall thickness (WT%) of pulmonary artery and RV collagen volume fraction (CVF) in both prevention and reversal protocols. We also found that salubrinal was capable of reducing endoplasmic reticulum stress and oxidative stress. The result of RNA-seq analysis revealed that chronic hypoxia stimulated the differential expression of a series of genes involved in cell cycle regulation and ventricular hypertrophy and so on. Some of these genes could be ameliorated by salubrinal. These results indicate that salubrinal could prevent and reverse well-established RV remodeling, and restore the genes and pathways altered in the right ventricles of rats exposed to hypobaric hypoxia. PMID- 27678417 TI - Immunostaining of proinflammatory cytokines in renal cortex and medulla of rats exposed to gold nanoparticles. AB - Recently, gold nanoparticles (GNPs) have shown promising applications in targeted drug delivery and contrast imaging. Although in vitro cytotoxicity of GNPs has been thoroughly studied, there are limited data on in vivo toxicity of GNPs. In this study, we evaluated the effects of intraperitoneally injected 10 nm and 50 nm GNPs (5 MUg/animal) on the expression of proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) on day 1 and day 5, post-exposure. The results of immunohistochemistry showed that both 10 nm and 50 nm GNPs induced an acute phase expression of proinflammatory cytokines in renal cortex and medulla. This proinflammatory response was comparatively more intense in renal medulla than cortex. All the three cytokines were undetectable in control cortex and medulla. In conclusion, both 10 nm and 50 nm GNPs caused an acute phase induction of proinflammatory cytokines in cortex and medulla of rat kidneys. An intense immunostaining of proinflammatory cytokines in renal medulla warrants further studies to evaluate the nephrotoxicity of GNPs to validate the safe application of GNPs for contrast imaging in renal insufficiency. PMID- 27678415 TI - Ethanol potentiates both GABAergic and glutamatergic signaling in the lateral habenula. AB - Ethanol's aversive property may limit it's use, but the underlying mechanisms are no well-understood. Emerging evidence suggests a critical role for the lateral habenula (LHb) in the aversive response to various drugs, including ethanol. We previously showed that ethanol enhances glutamatergic transmission and stimulates LHb neurons. GABAergic transmission, a major target of ethanol in many brain regions, also tightly regulates LHb activity. This study assessed the action of ethanol on LHb GABAergic transmission in rat brain slices. Application of ethanol accelerated spontaneous action potential firing of LHb neurons, and LHb activity was increased by the GABAA receptor antagonist gabazine, and ethanol-induced acceleration of LHb firing was further increased by gabazine. Additionally, ethanol potentiated GABAergic transmission (inhibitory postsynaptic currents, IPSCs) with an EC50 of 1.5 mM. Ethanol-induced potentiation of IPSCs was increased by a GABAB receptor antagonist; it was mimicked by dopamine, dopamine receptor agonists, and dopamine reuptake blocker, and was completely prevented by reserpine, which depletes store of catecholamine. Moreover, ethanol-induced potentiation of IPSCs involved cAMP signaling. Finally, ethanol enhanced simultaneously glutamatergic and GABAergic transmissions to the majority of LHb neurons: the potentiation of the former being greater than that of the latter, the net effect was increased firing. Since LHb excitation may contribute to aversion, ethanol-induced potentiation of GABAergic inhibition tends to reduce aversion. PMID- 27678418 TI - Using Foreign Virtual Patients With Medical Students in Germany: Are Cultural Differences Evident and Do They Impede Learning? AB - BACKGROUND: Learning with virtual patients (VPs) is considered useful in medical education for fostering clinical reasoning. As the authoring of VPs is highly demanding, an international exchange of cases might be desirable. However, cultural differences in foreign VPs might hamper learning success. OBJECTIVE: We investigated the need for support for using VPs from the United States at a German university, with respect to language and cultural differences. Our goal was to better understand potential implementation barriers of a intercultural VP exchange. METHODS: Two VPs were presented to 30 German medical students featuring a cultural background different from German standards with respect to diagnostic and therapeutic procedures, ethical aspects, role models, and language (as identified by a cultural adaptation framework). Participants were assigned to two groups: 14 students were advised to complete the cases without further instructions (basic group), and 16 students received written explanatory supplemental information specifically with regard to cultural differences (supplement group). Using a 6-point scale (6=strongly agree), we analyzed the results of an integrated assessment of learning success as well as an evaluation of cases by the students on usefulness for learning and potential issues regarding the language and cultural background. RESULTS: The German students found it motivating to work with cases written in English (6-point scale, 4.5 points). The clinical relevance of the VPs was clearly recognized (6 points), and the foreign language was considered a minor problem in this context (3 points). The results of the integrated learning assessment were similar in both groups (basic 53% [SD 4] vs supplement 52% [SD 4] correct answers, P=.32). However, students using the supplemental material more readily realized culturally different diagnostic and therapeutic strategies (basic 4 vs supplement 5 points, P=.39) and were less affirmative when asked about the transferability of cases to a German context (basic 5 vs supplement 3 points, P=.048). CONCLUSIONS: German students found English VPs to be highly clinically relevant, and they rated language problems much lower than they rated motivation to work on cases in English. This should encourage the intercultural exchange of VPs. The provision of supplemental explanatory material facilitates the recognition of cultural differences and might help prevent unexpected learning effects. PMID- 27678420 TI - From the Editor: What should be our target of treatment? PMID- 27678421 TI - JCL roundtable: Managing lipid disorders in young women. AB - The roundtable discussion in this issue will focus on the problems faced by young women with lipid disorders. This is often the source of confusion for the patient and physician because the myth continues that young women do not have complications of atherosclerosis as a result of elevated blood cholesterol. The essential role of women in bearing children during the early years of adulthood also produces difficult decisions because the mother and fetus are usually experiencing similar exposure to therapeutic regimens. We are joined in this discussion by Drs. Pamela Morris of the Medical University of South Carolina and Robert Wild of the University of Oklahoma Health Sciences Center. Dr Morris is an Internist, and Dr Wild is an Obstetrician and Gynecologist. Both are board certified in clinical lipidology and are actively publishing in this field. We have recorded this roundtable discussion during the National Lipid Association Scientific Sessions held in New Orleans during May 2016. PMID- 27678422 TI - Management strategies in patients with statin-associated muscle symptoms: What is the best strategy? PMID- 27678419 TI - The Cohesive Metastasis Phenotype in Human Prostate Cancer. AB - A critical barrier for the successful prevention and treatment of recurrent prostate cancer is detection and eradication of metastatic and therapy-resistant disease. Despite the fall in diagnoses and mortality, the reported incidence of metastatic disease has increased 72% since 2004. Prostate cancer arises in cohesive groups as intraepithelial neoplasia, migrates through muscle and leaves the gland via perineural invasion for hematogenous dissemination. Current technological advances have shown cohesive-clusters of tumor (also known as microemboli) within the circulation. Circulating tumor cell (CTC) profiles are indicative of disseminated prostate cancer, and disseminated tumor cells (DTC) are found in cohesive-clusters, a phenotypic characteristic of both radiation- and drug-resistant tumors. Recent reports in cell biology and informatics, coupled with mass spectrometry, indicate that the integrin adhesome network provides an explanation for the biophysical ability of cohesive-clusters of tumor cells to invade thorough muscle and nerve microenvironments while maintaining adhesion-dependent therapeutic resistance. Targeting cohesive-clusters takes advantage of the known ability of extracellular matrix (ECM) adhesion to promote tumor cell survival and represents an approach that has the potential to avoid the progression to drug- and radiotherapy-resistance. In the following review we will examine the evidence for development and dissemination of cohesive-clusters in metastatic prostate cancer. PMID- 27678423 TI - A review of PCSK9 inhibition and its effects beyond LDL receptors. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an integral role in the degradation of low-density lipoprotein receptors (LDL-R), making it an intriguing target for emerging pharmacotherapy. Two PCSK9 inhibitors, alirocumab and evolocumab, have been approved and are available in the United States and European Union. However, much of the PCSK9 story remains to be told. The pipeline for additional pharmacotherapy options is rich with several compounds under development, using alternative strategies for inhibiting PCSK9. Perhaps, more intriguing is the interaction between PCSK9 and non-LDL-R targets, including mediators of inflammation and immunological processes, which remain under intense investigation. This review will discuss the currently available PCSK9 inhibitors, the development of novel approaches to PCSK9 modulation, and the potential non LDL-R-mediated effects of PCSK9 inhibition. PMID- 27678424 TI - The risks of statin use in pregnancy: A systematic review. AB - Statins are contraindicated in pregnancy; however, as women delay pregnancy and statin use increases the risk of statin exposure in pregnancy is likely to rise. In contrast to some early reports that statins are teratogenic, more recent observational studies have called into question the teratogenic risk of statins. Therefore, whether statins are associated with congenital anomalies or other pregnancy complications remains an important clinical question. This article provides an up-to-date systematic review on the risks of statins in pregnancy. We conducted a literature search to identify relevant English language studies related to statin exposure and pregnancy. Single case reports, animal studies, studies only published in abstract form, and non-English language studies were excluded. A total of 16 clinical studies were included in this systematic review. Although early uncontrolled case series reported congenital anomalies associated with statin use, more recent observational studies did not report an increased risk of congenital anomalies with statin exposure in pregnancy when compared to control groups or the prevalence of congenital anomalies in the general population. Our findings show no clear relationship of congenital anomalies with statin use in pregnancy, and our study supports the findings that statins are probably not teratogenic. However, until more information is available, statins should still be avoided in pregnancy. PMID- 27678426 TI - Low advanced glycation end product diet improves the lipid and inflammatory profiles of prediabetic subjects. AB - BACKGROUND: Prediabetes is associated with risk for cardiovascular disease, and the first step in its management emphasizes lifestyle and diet modifications; however, modern diets are high in advanced glycation end products (dAGEs), derived from processing methods that exert a pivotal role in promoting atherosclerotic risk. OBJECTIVE: We studied the effect of low vs standard dAGE diets (L-dAGEs vs S-dAGEs) on lipid profile, inflammation, and cardiovascular risk in prediabetic subjects. METHODS: A 24-week randomized dietary intervention was conducted on 62 prediabetic subjects. We evaluated lipid profile, endogenous secretory receptors for AGEs, high-sensitivity C-reactive protein, arterial stiffness, and intima-media thickness. RESULTS: After 24 weeks, patients with L dAGEs showed a significant reduction of total cholesterol, apolipoprotein B, and low-density lipoprotein compared with controls (5.26 +/- 1.09 vs 5.53 +/- 0.87 mmol/L, P < .05; 0.77 +/- 0.25 vs 1.16 +/- 0.13 mmol/L, P < .05; and 3.53 +/- 0.93 vs 3.68 +/- 0.7 mmol/L, P < .05); with respect to baseline, high-sensitivity C-reactive protein levels were significantly reduced in the L-dAGEs group (0.21 [0.11-0.69] vs 0.12 [0.08-0.48] mg/dL, P < .05) but not in the S-dAGEs group. Endogenous secretory receptor for AGEs was similar in both the groups at baseline and at the 24-week follow-up. With respect to baseline, L-dAGE patients showed a significative reduction of intima-media thickness (0.77 [0.73-0.81] vs 0.73 [0.70 0.75] mm, P < .05). We did not observe the same reduction in S-dAGEs. No difference in arterial stiffness was found from baseline to follow-up in both the groups. CONCLUSIONS: L-dAGEs improved the lipid and inflammatory profiles of prediabetic subjects and seemed to reduce atherosclerotic burden compared with a standard diet. Further studies are needed to recommend this dietary regimen for prevention of cardiovascular risk in prediabetes. PMID- 27678427 TI - Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011-2012. AB - BACKGROUND: The 2013 American College of Cardiology/American Heart Association Cholesterol Management Guideline identifies 4 statin-eligible groups: (1) known atherosclerotic cardiovascular disease (ASCVD) aged >=21 years, (2) low-density lipoprotein cholesterol (LDL-C) >= 190 mg/dL (4.9 mmol/L) aged >=21 years, (3) diabetes mellitus aged 40 to 75 years with LDL-C 70 to 189 mg/dL (1.8-4.9 mmol/L), or (4) >=7.5% 10-year ASCVD risk aged 40 to 75 years with LDL-C 70 to 189 mg/dL (1.8-4.9 mmol/L). OBJECTIVES: We examined the number of statin-eligible US adults, statin use, LDL-C goal attainment, and adherence to lifestyle management. METHODS: We identified subjects from the US National Health and Nutrition Examination Survey 2011-2012 in the 4 statin-eligible groups, proportion on statin, proportion at recommended LDL-C levels using National Lipid Association goals (<70 mg/dL [1.8 mmol/L] for very high risk and <100 mg/dL [2.6 mmol/L] for others), and adherence to lifestyle measures. RESULTS: Of 5206 adults (representing 219 million), 1677 adults representing 62.6 million adults fit into 1 of the 4 statin-eligible groups. Statin use was 63.7% for the ASCVD, 61.4% for the LDL-C >= 190 mg/dL (4.9 mmol/L), 43.2% for the diabetes mellitus, and 27.2% for the 10-year risk >=7.5% groups. Of those on statins with LDL-C measured, 79.7%, 98.0%, 42.3%, and 46.8% were not at LDL-C goal. Adherence to recommended <6% calories from saturated fat ranged from 3.3% to 6.4% and >=40 minutes of physical activity >=3 times a week from 54.7% to 65.1% across statin-eligible groups. CONCLUSION: Many US adults eligible to receive statins based on American College of Cardiology/American Heart Association guidelines are not taking statins, and LDL-C levels still remain suboptimal. PMID- 27678425 TI - Mortality reduction in patients treated with long-term intensive lipid therapy: 25-year follow-up of the Familial Atherosclerosis Treatment Study-Observational Study. AB - BACKGROUND: Cardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia. OBJECTIVES: The clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study. METHODS: Of 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model. RESULTS: UC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11). CONCLUSIONS: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome. PMID- 27678428 TI - Effects of climatic factors on plasma lipid levels: A 5-year longitudinal study in a large Chinese population. AB - BACKGROUND: The rules and mechanisms of seasonal changes in plasma lipid levels, which may be related to annual rhythmicity of incidence and mortality of cardiovascular diseases, are still controversial. OBJECTIVE: The objectives of this study were to study the effects of climatic factors on plasma lipid levels and to preliminarily reveal mechanisms of annual rhythmicity of plasma lipid levels. METHODS: A longitudinal study was performed using health examination data of 5 consecutive years (47,270 subjects) in Jinan, China. The climate in Jinan is typical temperate continental monsoon climate with huge temperature difference between winter and summer (>30 degrees C). RESULTS: After considering and adjusting those classical lipid-associated risk factors, such as age, gender, diet, exercise, blood pressure, body weight, change of body weight, body mass index, glycemia, alanine aminotransferase, and creatinine, only air temperature could still significantly affect plasma lipid levels among the main climatic factors (humidity, precipitation, and so forth). For men, total cholesterol, high density lipoprotein cholesterol, and low-density lipoprotein cholesterol was decreased significantly 0.35, 0.18, and 0.06 mmol/L, respectively, whereas triglyceride was increased significantly 0.12 mmol/L for every 10 degrees C increase in air temperature. For women, total cholesterol and high-density lipoprotein cholesterol were decreased notably 0.73 and 0.32 mmol/L, and low density lipoprotein cholesterol was increased significantly 0.26 mmol/L for every 10 degrees C increase in air temperature, whereas triglyceride was not significantly affected by air temperature. CONCLUSION: Air temperature is an independent risk factor for plasma lipid levels besides those classical lipid associated risk factors. The annual air temperature fluctuations might be an important mechanism of the seasonal changes of lipids. PMID- 27678429 TI - The very high cardiovascular risk in heterozygous familial hypercholesterolemia: Analysis of 734 French patients. AB - BACKGROUND: Heterozygous familial hypercholesterolemia (heFH) is a genetic disease causing high levels of low-density lipoprotein cholesterol (LDL-C). Although this population is at high cardiovascular (CV) risk, the risk is variable within patients depending on additional risk factors. CV disease risk groups have been defined by the Nouvelle Societe Francophone d'Atherosclerose (NSFA) and by the National Lipid Association recommendations. OBJECTIVES: The study aimed to describe a sample of French heFH patients, comparing patients at very high risk (VHR) and patients at high risk in terms of demographic and clinical characteristics as well as biological measurements and disease management. METHODS: Cross-sectional retrospective analysis on 734 patients hospitalized after 2005 in 5 academic centers. RESULTS: When considering NSFA classification, 550 (74.9%) patients belonged to the VHR group. Most patients in the VHR group presented more than 1 risk factor, the most prevalent ones being Lp(a) > 50 mg/dL and smoking. Patients in the VHR group were older (50.6 vs 45.0 years old, P = .0002), and presented a higher body mass index (25.5 kg/m(2) vs 23.3 kg/m(2), P < .0001). The proportion of patients with carotid arterial plaque was higher in the VHR group (59.8% vs 48.6%, P = .06). Total cholesterol (2.41 g/L on average) and LDL-C (1.65 g/L on average) were not found to be significantly different. Maximum level of lipid-lowering treatments were used in 34% of cases in the VHR group, significantly higher than 16% in the high-risk group (P = .001). Very similar results were found when using the National Lipid Association recommendations. CONCLUSION: This study provides a detailed description of French heFH patients according to their CV risk. Patients with very high CV risk had usually more advanced carotid plaques and were treated with heavier lipid-lowering drugs although their LDL-C level remained similar. This highlights the significant burden of this population. PMID- 27678430 TI - Effects of the cholesteryl ester transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density lipoprotein particle subclasses. AB - BACKGROUND: TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. OBJECTIVE: To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non-ABCA1-driven CEC and on HDL particle distribution. METHODS: Total, non-ABCA1-, and ABCA1 specific CEC from J774 cells and HDL subclass distribution assessed by two dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215). RESULTS: Compared with placebo, total, non-ABCA1-, and ABCA1-specific CEC were increased dose dependently by up to 38%, 72%, and 28%, respectively, in patients randomized to 10 mg of TA-8995. PreBeta-1 HDL, the primary acceptor for ABCA1 driven cholesterol efflux, was increased by 36%. This increase in preBeta-1 HDL correlated significantly with the total and the ABCA1-driven CEC increase, whereas the high-density lipoprotein cholesterol (HDL-C) increase did not. CONCLUSION: TA-8995 dose dependently increased not only total and non-ABCA1 specific CEC but also ABCA1-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor-driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial. PMID- 27678431 TI - Familial hypercholesterolemia among unselected contemporary patients presenting with first myocardial infarction: Prevalence, risk factor burden, and impact on age at presentation. AB - BACKGROUND: Familial hypercholesterolemia (FH) is a hereditary disease carrying a substantial lifetime risk of coronary heart disease. OBJECTIVE: To assess the prevalence of FH and its impact on age at presentation among unselected patients with first myocardial infarction (MI). METHODS: In a multi-center cross sectional study, we identified 1381 unselected patients presenting with a first MI between 2010 and 2012. Clinical FH was assessed using both the Dutch Lipid Clinic Network (DLCN) criteria and the Simon Broome criteria. RESULTS: Based on the DLCN criteria, 2.0% of patients with first MI had "probable/definite" FH, whereas 4.7% had "possible" FH according to the Simon Broome criteria. In the 291 (21%) patients with premature MI, 6.9% had "probable/definite" FH (DLCN criteria), and 11.0% had "possible" FH (Simon Broome criteria). Nearly all premature "probable/definite" and "possible" FH patients had at least one additional marker of high cardiovascular risk including current smoking (72%-80%) and hypertension (40%-44%). In multivariable-adjusted linear regression modeling, patients with "probable/definite" FH using DLCN criteria had their first MI 14.6 years (95% confidence interval [CI], 9.6-19.6 years) earlier than non-FH patients. Likewise, "possible" FH patients using Simon Broome criteria were associated with having an MI 9.1 years (95% CI = 6.3-12.4) earlier than non-FH patients. CONCLUSION: Clinical FH is common and associated with markedly earlier age of first MI, especially when combined with additional markers of high risk, indicating an unmet need for earlier identification of FH to ensure global risk factor control. First MI constitutes a unique opportunity to detect families with unknown FH. PMID- 27678432 TI - A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia. AB - BACKGROUND: The efficacy and safety of atorvastatin in children/adolescents aged 10-17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed. OBJECTIVE: To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6-15 years with HeFH. METHODS: A total of 272 subjects aged 6-15 years with HeFH and low-density lipoprotein cholesterol (LDL-C) >=4.0 mmol/L (154 mg/dL) were enrolled in a 3-year study (NCT00827606). Subjects were initiated on atorvastatin (5 mg or 10 mg) with doses increased to up to 80 mg based on LDL-C levels. RESULTS: Mean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8% for subjects at Tanner stage (TS) 1 and 39.9% for TS >=2. There was no evidence of variations in the lipid-lowering efficacy of atorvastatin between the TS groups analyzed (1 vs >=2) or in subjects aged <10 vs >=10 years, and the treatment had no adverse effect on growth or maturation. Atorvastatin had a favorable safety and tolerability profile, and only 6 (2.2%) subjects discontinued because of adverse events. CONCLUSIONS: Atorvastatin over 3 years was efficacious, had no impact on growth/maturation, and was well tolerated in children and adolescents with HeFH aged 6-15 years. PMID- 27678433 TI - Assessment of postprandial triglycerides in clinical practice: Validation in a general population and coronary heart disease patients. AB - BACKGROUND: Previous studies have suggested that for clinical purposes, subjects with fasting triglycerides (TGs) between 89-180 mg/dl (1-2 mmol/l) would benefit from postprandial TGs testing. OBJECTIVE: To determine the postprandial TG response in 2 independent studies and validate who should benefit diagnostically from an oral-fat tolerance test (OFTT) in clinical practice. METHODS: A population of 1002 patients with coronary heart disease (CHD) from the CORDIOPREV clinical trial and 1115 white US subjects from the GOLDN study underwent OFTTs. Subjects were classified into 3 groups according to fasting cut points of TGs to predict the usefulness of OFTT: (1) TG < 89 mg/dl (<1 mmol/l); (2) TG, 89-180 mg/dl (1-2 mmol/l); and (3) TG > 180 mg/dl (>2 mmol/l). Postprandial TG concentration at any point > 220 mg/dl (>2.5 mmol/l) has been pre-established as an undesirable postprandial response. RESULTS: Of the total, 49% patients with CHD and 42% from the general population showed an undesirable response after the OFTT. The prevalence of undesirable postprandial TG in the CORDIOPREV clinical trial was 12.8, 50.3, and 89.7%, in group 1, 2, and 3, respectively (P < .001) and 11.2, 58.1, and 97.5% in group 1, 2, and 3, respectively (P < .001) in the GOLDN study. CONCLUSIONS: These two studies validate the predictive values reported in a previous consensus. Moreover, the findings of the CORDIOPREV and GOLDN studies show that an OFTT is useful to identify postprandial hyperlipidemia in subjects with fasting TG between 1-2 mmol/l (89-180 mg/dL), because approximately half of them have hidden postprandial hyperlipidemia, which may influence treatment. An OFTT does not provide additional information regarding postprandial hyperlipidemia in subjects with low TG (<1 mmol/l, <89 mg/dL) or increased TG (>2 mmol/l, >180 mg/dl). PMID- 27678435 TI - Familial hypercholesterolemia in a large ambulatory population: Statin use, optimal treatment, and identification for advanced medical therapies. AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease resulting in elevated serum low-density lipoprotein cholesterol (LDL-C) levels. Patients with FH have a very high lifetime risk of cardiovascular disease, but FH often goes unrecognized in clinical care. New treatments including PCSK9 inhibitors are now available for this population, and the use of the electronic record may be able to help identify potential patients for therapy. OBJECTIVES: The goal of this study was to determine the period prevalence of FH in a large ambulatory care population, including the homozygous form. In addition, use of cholesterol lowering therapy in individuals with FH was characterized. METHODS: A retrospective analysis was carried out among patients seen in an upper Midwest health care system between 2009 and 2012. In a search of electronic health records (EHR) and using the current National Lipid Association guidelines, FH patients (including homozygous cases) were identified based on age and highest LDL-C. Statin therapy was characterized according to current FH treatment guidelines. RESULTS: There were 391,166 individuals with available measures during the study timeframe. Of these, 841 were identified as having probable HeFH, representing a prevalence of 0.21% (about 1 in 470 patients) in this population. HoFH was identified as probable in 6 patients. For the total group, two-thirds of FH patients were on a statin, but only half were treated adequately. The remaining one-third of FH patients were not on statin therapy, with only 27% of those not on statin therapy having a documented statin intolerance. CONCLUSIONS: FH is often underdiagnosed and suboptimally treated in clinical practice. Statin therapy in this population rarely went beyond low moderate doses. These findings support EHR-based population health efforts to initiate an FH cascade-screening model and ensure higher quality care for this high-risk population and identify those who may benefit from advanced therapy. PMID- 27678434 TI - Lifestyle intervention enhances high-density lipoprotein function among patients with metabolic syndrome only at normal low-density lipoprotein cholesterol plasma levels. AB - BACKGROUND: Metabolic syndrome (MetS) is associated with altered lipoprotein metabolism and impairment in the functionality of small, dense high-density lipoprotein (HDL) particles secondary to compositional alterations. OBJECTIVE: The objective of this study was to investigate the capacity of a lifestyle program to improve the composition and antioxidative function (AOX) of small dense HDL3c in MetS. METHODS: Patients with MetS (n = 33) not taking lipid lowering drugs were recruited to follow a 12-week educational program to reduce caloric intake and to increase physical activity. HDL subfractions were preparatively isolated by isopycnic density-gradient ultracentrifugation. AOX of HDL3c was assessed as its capacity to inhibit low-density lipoprotein oxidation induced by an azoinitiator. RESULTS: AOX of HDL3c was significantly improved (mean reduction in the propagation rate of low-density lipoprotein oxidation by HDL3c, -6.8%, P = .03) and systemic oxidative stress, assessed as plasma levels of 8-isoprostanes, tended to decrease in normocholesterolemic MetS patients (low density lipoprotein cholesterol [LDL-C] < 130 mg/dL) but not in patients with elevated LDL-C levels and in the whole study population. In both the whole study population and the normocholesterolemic subgroup, lifestyle intervention resulted in a significant degree of normalization of HDL3c composition, (enrichment in apolipoprotein A-I and cholesteryl esters, depletion in triglycerides), which was more pronounced at LDL-C < 130 mg/dL. CONCLUSION: In patients with MetS, a lifestyle program improves AOX of small, dense HDL in subjects with normal LDL-C levels. Correction of HDL composition, involving partial normalization of apoA-I content and core lipid composition, 2 central features of the lipid hydroperoxide inactivating capacity of HDL, may account for this effect. PMID- 27678436 TI - Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country. AB - BACKGROUND: Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. OBJECTIVES: The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. METHODS: We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH. RESULTS: We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 +/- 7.2%, with time-averaged mean lowering of 34.9 +/- 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost. CONCLUSION: LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed. PMID- 27678438 TI - Nigella sativa oil with a calorie-restricted diet can improve biomarkers of systemic inflammation in obese women: A randomized double-blind, placebo controlled clinical trial. AB - BACKGROUND: Inflammation is one of the primary mechanisms in the development of metabolic complications. Although anti-inflammatory characteristics of Nigella sativa (NS) have been indicated in animal models, clinical trials related to the effects of NS on inflammatory parameters are relatively scarce. OBJECTIVE: The aim of the present study was to determine the effects of NS oil combined with a calorie-restricted diet on systemic inflammatory biomarkers in obese women. METHODS: In this double-blind placebo-controlled randomized clinical trial, 90 volunteer obese (body mass index = 30-34.9 kg/m(2)) women aged 25-50 years were recruited. Participants were randomly divided into two groups, an intervention group (n = 45) and a placebo group (n = 45). Each group received either: (1) a low-calorie diet with 3 g/day of NS oil or (2) a low-calorie diet with 3 g/day placebo for 8 weeks. RESULTS: A total of 84 females (intervention group = 43; placebo group = 41) completed the trial. Subjects in the intervention group did not report any side effects with the NS oil supplementation. NS oil decreased serum levels of tumor necrosis factor-alpha (-40.8% vs -16.1%, P = .04) and high sensitivity C-reactive protein (-54.5% vs -21.4%, P = .01) compared to the placebo group. However, there were no significant changes in interleukin-6 levels (-8.6 vs -2.4%, P = .6) in the NS group compared to the placebo group. CONCLUSIONS: NS oil supplementation combined with a calorie-restricted diet may modulate systemic inflammatory biomarkers in obese women. However, more studies are needed to clarify the efficacy of NS oil as an adjunct therapy to improve inflammatory parameters in obese subjects. PMID- 27678439 TI - Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. AB - BACKGROUND: Ezetimibe added to statin therapy further reduces LDL-C and clinical atherosclerotic cardiovascular disease compared to statin alone. However, the number of effective and safe oral agents for patients not at LDL-C goal is limited. In prior clinical trials, gemcabene reduced LDL-C and was generally well tolerated in nearly 900 patients treated for up to 12 weeks. OBJECTIVE: To evaluate the LDL-C lowering and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. METHODS: This was an 8-week, double blind, placebo-controlled, randomized, phase 2 study in men and postmenopausal women >=18 and <=65 years of age with LDL-C >=130 mg/dL (3.4 mmol/L) while on low intensity to high-intensity stable statin (the majority on moderate intensity) therapy. Sixty-six patients were randomized 1:1:1 to gemcabene 300 mg, 900 mg, or placebo QD. RESULTS: Gemcabene 300 mg and 900 mg produced a mean percent change in LDL-C of -23.4 +/- 4.7% (P = .005) and -27.7 +/- 4.3% (P < .001), respectively, vs -6.2 +/- 4.3% for placebo. The median percent change in CRP was 26.1% (P = .196) and -53.9% (P < .001) for gemcabene 300 mg and 900 mg, respectively, vs -11.1% for placebo. Gemcabene 300 mg and 900 mg were well tolerated with no significant difference in AEs compared to placebo. CONCLUSIONS: Gemcabene as add-on to stable statin therapy demonstrated additional dose dependent and statistically significant reductions in LDL-C of >20% and CRP >40% compared to placebo. The results support gemcabene-continued development for patients requiring LDL-C lowering beyond that provided by background statin therapy. PMID- 27678437 TI - Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification. AB - BACKGROUND: Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL C). OBJECTIVES: Whether LDL-P is associated with subclinical atherosclerosis, independent of LDL-C, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis. METHODS: We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined. RESULTS: LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made. CONCLUSIONS: In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. PMID- 27678441 TI - Rapid identification of familial hypercholesterolemia from electronic health records: The SEARCH study. AB - BACKGROUND: Little is known about prevalence, awareness, and control of familial hypercholesterolemia (FH) in the United States. OBJECTIVE: To address these knowledge gaps, we developed an ePhenotyping algorithm for rapid identification of FH in electronic health records (EHRs) and deployed it in the Screening Employees And Residents in the Community for Hypercholesterolemia (SEARCH) study. METHODS: We queried a database of 131,000 individuals seen between 1993 and 2014 in primary care practice to identify 5992 (mean age 52 +/- 13 years, 42% men) patients with low-density lipoprotein cholesterol (LDL-C) >=190 mg/dL, triglycerides <400 mg/dL and without secondary causes of hyperlipidemia. RESULTS: Our EHR-based algorithm ascertained the Dutch Lipid Clinic Network criteria for FH using structured data sets and natural language processing for family history and presence of FH stigmata on physical examination. Blinded expert review revealed positive and negative predictive values for the SEARCH algorithm at 94% and 97%, respectively. The algorithm identified 32 definite and 391 probable cases with an overall FH prevalence of 0.32% (1:310). Only 55% of the FH cases had a diagnosis code relevant to FH. Mean LDL-C at the time of FH ascertainment was 237 mg/dL; at follow-up, 70% (298 of 423) of patients were on lipid-lowering treatment with 80% achieving an LDL-C <=100 mg/dL. Of treated FH patients with premature CHD, only 22% (48 of 221) achieved an LDL-C <=70 mg/dL. CONCLUSIONS: In a primary care setting, we found the prevalence of FH to be 1:310 with low awareness and control. Further studies are needed to assess whether automated detection of FH in EHR improves patient outcomes. PMID- 27678440 TI - US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry. AB - BACKGROUND: In the US familial hypercholesterolemia (FH), patients are underidentified, despite an estimated prevalence of 1:200 to 1:500. Criteria to identify FH patients include Simon Broome, Dutch Lipid Clinic Network (DLCN), or Make Early Diagnosis to Prevent Early Deaths (MEDPED). The use of these criteria in US clinical practices remains unclear. OBJECTIVE: To characterize the FH diagnostic criteria applied by US lipid specialists participating in the FH Foundation's CASCADE FH (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia) patient registry. METHODS: We performed an observational, cross-sectional analysis of diagnostic criteria chosen for each adult patient, both overall and by baseline patient characteristics, at 15 clinical sites that had contributed data to the registry as of September 8, 2015. A sample of 1867 FH adults was analyzed. The median age at FH diagnosis was 50 years, and the median pretreatment low-density lipoprotein cholesterol (LDL-C) value was 238 mg/dL. The main outcome was the diagnostic criteria chosen. Diagnostic criteria were divided into five nonexclusive categories: "clinical diagnosis," MEDPED, Simon Broome, DLCN, and other. RESULTS: Most adults enrolled in CASCADE FH (55.0%) received a "clinical diagnosis." The most commonly used formal criteria was Simon-Broome only (21%), followed by multiple diagnostic criteria (16%), MEDPED only (7%), DLCN only (1%), and other (0.5%), P < .0001. Of the patients with only a "clinical diagnosis," 93% would have met criteria for Simon Broome, DLCN, or MEDPED based on the data available in the registry. CONCLUSIONS: Our findings demonstrate heterogeneity in the application of FH diagnostic criteria in the United States. A nationwide consensus definition may lead to better identification, earlier treatment, and ultimately CHD prevention. PMID- 27678443 TI - An evidence-based analysis of the National Lipid Association recommendations concerning non-HDL-C and apoB. AB - BACKGROUND: The National Lipid Association (NLA) selected non-HDL-C as its prime index of the cardiovascular risk associated with the apoB lipoproteins. ApoB was recommended only as an optional secondary target after low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) targets were achieved. OBJECTIVE: The aims of this analysis were to determine whether (1) all relevant uses of apoB were considered by the NLA; (2) all the relevant evidence was considered by the NLA panel; and (3) all the evidence that was considered was interpreted correctly. RESULTS: (1) The utility of apoB in the diagnosis of the atherogenic dyslipoproteinemias was not considered. (2) All the relevant observational studies were not identified, and some that were cited were incorrectly interpreted. In particular, an equal hazard ratio for two markers in a group does not mean they will predict risk equally in individuals within the group in whom they are discordant. This matters because discordance analysis consistently demonstrates apoB and LDL particle number are more accurate measures of cardiovascular risk than LDL-C/non-HDL-C. (3) The target levels of apoB selected by the NLA are too high relative to the levels selected for LDL-C and non-HDL-C. CONCLUSIONS: The review of the evidence by the NLA was incomplete. More complete examination of the evidence indicates that apoB is a more accurate marker of cardiovascular risk than non-HDL-C and that the practice of lipidology would be improved by inclusion of apoB along with lipoprotein lipids in routine clinical care. PMID- 27678444 TI - Rapid resolution of xanthelasmas after treatment with alirocumab. AB - Xanthelasmas are superficial fat deposits around the eyelids commonly present in different hyperlipidemias and associated with increased cardiovascular risk. Statins or other lipid-lowering treatments do not usually modify them. We present the case of a middle-age man with severe high levels of LDL cholesterol from youth due to a genetically defined heterozygous familiar hypercholesterolemia (HeFH). He presented large xanthelasmas of both inner eyelids in spite of long term treatment with statins and ezetimibe that disappeared after treatment with alirocumab75 mg every 2 weeks for 26 months. His LDL cholesterol went from 164 mg/dL to 47 mg/dL with alirocumab. Xanthelasma regression was not previously reported with lipid-lowering drugs in HeFH. This case demonstrates that regression of skin lipid lesions can be achieved with very low LDL cholesterol concentrations. PMID- 27678445 TI - Tendon xanthomas: Not always familial hypercholesterolemia. AB - Tendon xanthoma are most commonly associated with Familial Hypercholesterolemia, but the differential diagnosis includes sitosterolemia and cerebrotendinous xanthomatosis (CTX). The case presented here is of a 48-year old male with large tendon xanthomas attributable to CTX. CTX is a rare, recessive disorder caused by mutations in the CYP27A1 gene. The resultant defect in bile acid synthesis leads to cholestanol deposition in different tissues in the body, including tendons. CTX is associated with neurologic symptoms and a reduced life expectancy. Treatment consists of bile acid supplementation in combination with a statin. When patients present with tendon xanthomas and FH is ruled out, clinicians should consider CTX as a possible diagnosis. PMID- 27678442 TI - Body mass index and glycemic control influence lipoproteins in children with type 1 diabetes. AB - BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) have an extremely high risk of cardiovascular disease (CVD) morbidity and mortality. It is well known that dyslipidemia is a subclinical manifestation of atherosclerosis. OBJECTIVE: To analyze presence and predicting factors of lipoprotein abnormalities prevalent in children with T1DM and whether race-specific differences exist between non Hispanic white (NHW) and non-Hispanic black (NHB) in the lipoprotein characteristics. METHODS: A retrospective electronic chart review including 600 (123 NHB and 477 NHW) T1DM patients aged 7.85 +/- 3.75 years who underwent lipoprotein analysis. RESULTS: Relative to NHW counterparts, NHB T1DM subjects had a higher HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), apoB 100, lipoprotein (a), and high-density lipoprotein cholesterol (HDL c), HDL-2, and HDL-3. Body mass index (BMI) was positively associated with TC, LDL-c, apoB 100, and non-HDL-c and inversely associated with HDL, HDL-2, and HDL 3. HbA1c was positively associated with TC, LDL-c, apoB 100, non-HDL-c, and HDL 3. Multilinear regression analysis demonstrated that HbA1c was positively associated with apoB 100 in both NHB and NHW, and BMI was a positive determinant of apoB 100 in NHW only. CONCLUSION: Poor glycemic control and high BMI may contribute to abnormal lipoprotein profiles. Glycemic control (in NHB and NHW) and weight management (in NHW) may have significant implications in T1DM. ApoB 100 concentrations in subjects with T1DM were determined by modifiable risk factors, BMI, HbA1C, and blood pressure, indicating the importance of adequate weight, glycemic, and blood pressure control for better diabetes care and likely lower CVD risk. PMID- 27678446 TI - Ischemic stroke in a young adult with extremely elevated lipoprotein(a): A case report and review of literature. AB - Lipoprotein(a) [Lp(a)] is an apolipoprotein(a) molecule bound to 1 apolipoprotein B-100. Elevated levels of Lp(a) are thought to be an independent risk factor for atherosclerosis and to promote thrombosis through incompletely understood mechanisms. We report a 34-year-old man with an ischemic stroke in the setting of an extremely high Lp(a) level-212 mg/dL. He developed severe carotid artery stenosis over a 6-year period and had thrombus formation post-carotid endarterectomy. To our knowledge, this case is unique because the Lp(a) is the highest reported level in a patient without renal disease. Moreover, this is the first reported case of the youngest individual with a stroke presumably related to development of carotid plaque over a 6-year period. The thrombotic complication after endarterectomy may have been related to the prothrombotic properties of Lp(a). Of note, the Lp(a) level did not respond to atorvastatin but did decrease 15% after aspirin 325 mg was added although his Lp(a) levels were variable, and it is not clear that this was cause and effect. This case highlights the need to better understand the relation between Lp(a) and vascular disease and the need to screen family members for elevated Lp(a). We also review treatment options to lower Lp(a) and ongoing clinical trials of newer lipid lowering drugs that can also lower Lp(a). PMID- 27678447 TI - Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk. AB - We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family. PMID- 27678448 TI - Rescue therapy with PCSK9 inhibitors for patients with delayed diagnosis of heterozygous familial hypercholesterolemia: Redressing the balance of missed opportunities. PMID- 27678449 TI - Options to consider when treating lysosomal acid lipase deficiency. PMID- 27678450 TI - Response to "Letter to the Editor by Drs Block and Razani". PMID- 27678451 TI - Mechanistic insight into effect of doping of Ni on CO2 reduction on the (111) facet of Cu: thermodynamic and kinetic analyses of the elementary steps. AB - A systematic mechanistic investigation of CO2 reduction on a Ni-modified Cu(111) surface is performed based on an extensive set of density functional theory (DFT) calculations by focusing on the hydrocarbon CH4 formation pathways. By carefully analyzing reduction pathways on the Ni-modified Cu(111) surface, some important mechanistic information is deduced. The presence of Ni stabilizes all reaction intermediates, and thus reduces the activation barrier for almost all CO2 reduction steps. Most importantly, it can considerably lower than the activation barrier of CO2 hydrogenative dissociation into CO, which is the rate-determining step of CO2 reduction on a pure Cu(111) surface. Thus, the doping of Ni atom is able to activate CO2, leading to enhanced surface activity of CO2 reduction into hydrocarbons. Notably, the activation barriers that are required for CH4 and CH3OH formation are almost all easily overcome through the thermoactive process at ambient temperatures after doping of Ni atom. Thus, a higher CH4 and CH3OH yield may be expected in the presence of the doped Ni atom. Thermodynamic analyses indicate that doping of Ni may reduce the overpotential of CO formation through CO2 hydrogenative dissociation. On this basis, two decriptors may be proposed in order to describe the catalytic activity of Cu-based catalysts for CO2 reduction, and a perfect Cu-based alloy in CO2 reduction should moderately bind CO and form and reduce CO more easily. Simutaneously, CO hydrogenation occurs more easily on the (111) facet of Ni-modified Cu than dimerization, thereby the selectivity of (111) facet of Cu on production CH4 is further confirmed to some degree. The present study reveals a rich reaction chemistry and provides new insights to guide the rational design of Cu-based alloy catalysts for hydrocarbons formation from CO2 reduction. Graphical Abstract Reduction pathways of CO2 into hydrocarbons?. PMID- 27678452 TI - Changing of the guards: EMA warning on paternal use of mycophenolate mofetil: An unnecessary and insufficiently substantiated precaution. PMID- 27678453 TI - The Added Value of Circulating Tumor Cell Enumeration to Standard Markers in Assessing Prognosis in a Metastatic Castration-Resistant Prostate Cancer Population. AB - Purpose: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease for which better prognostic models for survival are needed. We examined the added value of circulating tumor cell (CTC) enumeration relative to common prognostic laboratory measures from patients with CRPC.Methods: Utility of CTC enumeration as a baseline and postbaseline prognostic biomarker was examined using data from two prospective randomized registration-directed trials (COU-AA-301 and ELM-PC4) within statistical models used to estimate risk for survival. Discrimination and calibration were used to measure model predictive accuracy and the added value for CTC enumeration in the context of a Cox model containing albumin, lactate dehydrogenase (LDH), PSA, hemoglobin, and alkaline phosphatase (ALK). Discrimination quantifies how accurately a risk model predicts short-term versus long-term survivors. Calibration measures the closeness of actual survival time to the predicted survival time.Results: Adding CTC enumeration to a model containing albumin, LDH, PSA, hemoglobin, and ALK ("ALPHA") improved its discriminatory power. The weighted c-index for ALPHA without CTCs was 0.72 (SE, 0.02) versus 0.75 (SE, 0.02) for ALPHA + CTCs. The increase in discrimination was restricted to the lower-risk cohort. In terms of calibration, adding CTCs produced a more accurate model-based prediction of patient survival. The absolute prediction error for ALPHA was 3.95 months (SE, 0.28) versus 3.75 months (SE, 0.22) for ALPHA + CTCs.Conclusions: Addition of CTC enumeration to standard measures provides more accurate assessment of patient risk in terms of baseline and postbaseline prognosis in the mCRPC population. Clin Cancer Res; 23(8); 1967-73. (c)2016 AACR. PMID- 27678454 TI - Signal Transduction and Activator of Transcription-3 (STAT3) in Patients with Colorectal Cancer: Associations with the Phenotypic Features of the Tumor and Host. AB - Purpose: In patients with colorectal cancer, a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL6/JAK/STAT3 pathway. The present study examines the relationship between tumor total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses, and survival in patients undergoing resection of stage I-III colorectal cancer.Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumor cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density, and Klintrup-Makinen grade) and systemic inflammatory responses and cancer-specific survival were examined.Results: A total of 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r = 0.363; P < 0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r = 0.130; P = 0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P = 0.012), CD8+ (P = 0.003), and FOXP3+ T lymphocytes (P = 0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P = 0.004).The combination of nuclear STAT3/pSTAT3 stratified 5-year survival from 81% to 62% (P = 0.012), however, was not associated with survival independent of venous invasion, tumor perforation, or tumor budding.Conclusions: In patients undergoing colorectal cancer resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Upregulation of tumor STAT3 may be an important mechanism whereby the tumor deregulates local and systemic inflammatory responses. Clin Cancer Res; 23(7); 1698-709. (c)2016 AACR. PMID- 27678455 TI - Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer. AB - Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19 In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro, inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. Clin Cancer Res; 23(7); 1829-40. (c)2016 AACR. PMID- 27678456 TI - A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. AB - Purpose: Salt-inducible kinase 2 (SIK2) is a centrosome kinase required for mitotic spindle formation and a potential target for ovarian cancer therapy. Here, we examine the effects of a novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in ovarian cancer.Experimental Design: SIK2 expression was determined in ovarian cancer tissue samples and cell lines. ARN 3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures and xenografts of ovarian cancer cell lines. SIK2 siRNA and ARN-3236 were compared for their ability to produce nuclear-centrosome dissociation, inhibit centrosome splitting, block mitotic progression, induce tetraploidy, trigger apoptotic cell death, and reduce AKT/survivin signaling.Results: SIK2 is overexpressed in approximately 30% of high-grade serous ovarian cancers. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 MUmol/L, where the IC50 of ARN-3236 was inversely correlated with endogenous SIK2 expression (Pearson r = -0.642, P = 0.03). ARN 3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts. In at least three cell lines, a synergistic interaction was observed. ARN-3236 uncoupled the centrosome from the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy. ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression.Conclusions: ARN-3236 is the first orally available inhibitor of SIK2 to be evaluated against ovarian cancer in preclinical models and shows promise in inhibiting ovarian cancer growth and enhancing paclitaxel chemosensitivity. Clin Cancer Res; 23(8); 1945-54. (c)2016 AACR. PMID- 27678458 TI - Biomarkers of Response and Resistance to DNA Repair Targeted Therapies. AB - Drugs targeting DNA damage repair (DDR) pathways are exciting new agents in cancer therapy. Many of these drugs exhibit synthetic lethality with defects in DNA repair in cancer cells. For example, ovarian cancers with impaired homologous recombination DNA repair show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Understanding the activity of different DNA repair pathways in individual tumors, and the correlations between DNA repair function and drug response, will be critical to patient selection for DNA repair targeted agents. Genomic and functional assays of DNA repair pathway activity are being investigated as potential biomarkers of response to targeted therapies. Furthermore, alterations in DNA repair function generate resistance to DNA repair targeted agents, and DNA repair states may predict intrinsic or acquired drug resistance. In this review, we provide an overview of DNA repair targeted agents currently in clinical trials and the emerging biomarkers of response and resistance to these agents: genetic and genomic analysis of DDR pathways, genomic signatures of mutational processes, expression of DNA repair proteins, and functional assays for DNA repair capacity. We review biomarkers that may predict response to selected DNA repair targeted agents, including PARP inhibitors, inhibitors of the DNA damage sensors ATM and ATR, and inhibitors of nonhomologous end joining. Finally, we introduce emerging categories of drugs targeting DDR and new strategies for integrating DNA repair targeted therapies into clinical practice, including combination regimens. Generating and validating robust biomarkers will optimize the efficacy of DNA repair targeted therapies and maximize their impact on cancer treatment. Clin Cancer Res; 22(23); 5651-60. (c)2016 AACR. PMID- 27678457 TI - The MAPK Pathway Regulates Intrinsic Resistance to BET Inhibitors in Colorectal Cancer. AB - Purpose: The bromodomain and extra-terminal domain (BET) family proteins are epigenetic readers for acetylated histone marks. Emerging BET bromodomain inhibitors have exhibited antineoplastic activities in a wide range of human cancers through suppression of oncogenic transcription factors, including MYC. However, the preclinical activities of BET inhibitors in advanced solid cancers are moderate at best. To improve BET-targeted therapy, we interrogated mechanisms mediating resistance to BET inhibitors in colorectal cancer.Experimental Design: Using a panel of molecularly defined colorectal cancer cell lines, we examined the impact of BET inhibition on cellular proliferation and survival as well as MYC activity. We further tested the ability of inhibitors targeting the RAF/MEK/ERK (MAPK) pathway to enhance MYC suppression and circumvent intrinsic resistance to BET inhibitors. Key findings were validated using genetic approaches.Results: BET inhibitors as monotherapy moderately reduced colorectal cancer cell proliferation and MYC expression. Blockade of the MAPK pathway synergistically sensitized colorectal cancer cells to BET inhibitors, leading to potent apoptosis and MYC downregulation in vitro and in vivo A combination of JQ1 and trametinib, but neither agent alone, induced significant regression of subcutaneous colorectal cancer xenografts.Conclusions: Our findings suggest that the MAPK pathway confers intrinsic resistance to BET inhibitors in colorectal cancer and propose an effective combination strategy for the treatment of colorectal cancer. Clin Cancer Res; 23(8); 2027-37. (c)2016 AACR. PMID- 27678459 TI - Computerized prescriber order entry-related patient safety reports: analysis of 2522 medication errors. AB - Objective: To examine medication errors potentially related to computerized prescriber order entry (CPOE) and refine a previously published taxonomy to classify them. Materials and Methods: We reviewed all patient safety medication reports that occurred in the medication ordering phase from 6 sites participating in a United States Food and Drug Administration-sponsored project examining CPOE safety. Two pharmacists independently reviewed each report to confirm whether the error occurred in the ordering/prescribing phase and was related to CPOE. For those related to CPOE, we assessed whether CPOE facilitated (actively contributed to) the error or failed to prevent the error (did not directly cause it, but optimal systems could have potentially prevented it). A previously developed taxonomy was iteratively refined to classify the reports. Results: Of 2522 medication error reports, 1308 (51.9%) were related to CPOE. Of these, CPOE facilitated the error in 171 (13.1%) and potentially could have prevented the error in 1137 (86.9%). The most frequent categories of "what happened to the patient" were delays in medication reaching the patient, potentially receiving duplicate drugs, or receiving a higher dose than indicated. The most frequent categories for "what happened in CPOE" included orders not routed to or received at the intended location, wrong dose ordered, and duplicate orders. Variations were seen in the format, categorization, and quality of reports, resulting in error causation being assignable in only 403 instances (31%). Discussion and Conclusion: Errors related to CPOE commonly involved transmission errors, erroneous dosing, and duplicate orders. More standardized safety reporting using a common taxonomy could help health care systems and vendors learn and implement prevention strategies. PMID- 27678460 TI - MeSHDD: Literature-based drug-drug similarity for drug repositioning. AB - Objective: Drug repositioning is a promising methodology for reducing the cost and duration of the drug discovery pipeline. We sought to develop a computational repositioning method leveraging annotations in the literature, such as Medical Subject Heading (MeSH) terms. Methods: We developed software to determine significantly co-occurring drug-MeSH term pairs and a method to estimate pair wise literature-derived distances between drugs. Results: We found that literature-based drug-drug similarities predicted the number of shared indications across drug-drug pairs. Clustering drugs based on their similarity revealed both known and novel drug indications. We demonstrate the utility of our approach by generating repositioning hypotheses for the commonly used diabetes drug metformin. Conclusion: Our study demonstrates that literature-derived similarity is useful for identifying potential repositioning opportunities. We provided open-source code and deployed a free-to-use, interactive application to explore our database of similarity-based drug clusters (available at http://apps.chiragjpgroup.org/MeSHDD/ ). PMID- 27678461 TI - IT-CARES: an interactive tool for case-crossover analyses of electronic medical records for patient safety. AB - Background: The significant risk of adverse events following medical procedures supports a clinical epidemiological approach based on the analyses of collections of electronic medical records. Data analytical tools might help clinical epidemiologists develop more appropriate case-crossover designs for monitoring patient safety. Objective: To develop and assess the methodological quality of an interactive tool for use by clinical epidemiologists to systematically design case-crossover analyses of large electronic medical records databases. Material and Methods: We developed IT-CARES, an analytical tool implementing case crossover design, to explore the association between exposures and outcomes. The exposures and outcomes are defined by clinical epidemiologists via lists of codes entered via a user interface screen. We tested IT-CARES on data from the French national inpatient stay database, which documents diagnoses and medical procedures for 170 million inpatient stays between 2007 and 2013. We compared the results of our analysis with reference data from the literature on thromboembolic risk after delivery and bleeding risk after total hip replacement. Results: IT CARES provides a user interface with 3 columns: (i) the outcome criteria in the left-hand column, (ii) the exposure criteria in the right-hand column, and (iii) the estimated risk (odds ratios, presented in both graphical and tabular formats) in the middle column. The estimated odds ratios were consistent with the reference literature data. Discussion: IT-CARES may enhance patient safety by facilitating clinical epidemiological studies of adverse events following medical procedures. The tool's usability must be evaluated and improved in further research. PMID- 27678462 TI - AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility. AB - AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied. PMID- 27678463 TI - Morphometric comparison by the ISAS(r) CASA-DNAf system of two techniques for the evaluation of DNA fragmentation in human spermatozoa. AB - DNA fragmentation has been shown to be one of the causes of male infertility, particularly related to repeated abortions, and different methods have been developed to analyze it. In the present study, two commercial kits based on the SCD technique (Halosperm (r) and SDFA) were evaluated by the use of the DNA fragmentation module of the ISAS (r) v1 CASA system. Seven semen samples from volunteers were analyzed. To compare the results between techniques, the Kruskal Wallis test was used. Data were used for calculation of Principal Components (two PCs were obtained), and subsequent subpopulations were identified using the Halo, Halo/Core Ratio, and PC data. Results from both kits were significantly different (P < 0.001). In each case, four subpopulations were obtained, independently of the classification method used. The distribution of subpopulations differed depending on the kit used. From the PC data, a discriminant analysis matrix was obtained and a good a posteriori classification was obtained (97.1% for Halosperm and 96.6% for SDFA). The present results are the first approach on morphometric evaluation of DNA fragmentation from the SCD technique. This approach could be used for the future definition of a classification matrix surpassing the current subjective evaluation of this important sperm factor. PMID- 27678464 TI - Morphometry and subpopulation structure of Holstein bull spermatozoa: variations in ejaculates and cryopreservation straws. AB - Sperm quality is evaluated for the calculation of sperm dosage in artificial reproductive programs. The most common parameter used is motility, but morphology has a higher potential as a predictor of genetic quality. Morphometry calculations from CASA-Morph technology improve morphological evaluation and allow mathematical approaches to the problem. Semen from 28 Holstein bulls was collected by artificial vagina, and several ejaculates were studied. After general evaluation, samples were diluted, packaged in 0.25 ml straws, and stored in liquid nitrogen. Two straws per sample were thawed, and slides were processed and stained with Diff-Quik. Samples were analyzed by a CASA-Morph system for eight morphometric parameters. In addition to the "classical" statistical approach, based on variance analysis (revealing differences between animals, ejaculates, and straws), principal component (PC) analysis showed that the variables were grouped into PC1, related to size, and PC2 to shape. Subpopulation structure analysis showed four groups, namely, big, small, short, and narrow from their dominant characteristics, representing 31.0%, 27.3%, 24.1%, and 17.7% of the total population, respectively. The distributions varied between animals and ejaculates, but between straws, there were no differences in only four animals. This modern approach of considering an ejaculate sperm population as divided into subpopulations reflecting quantifiable parameters generated by CASA-Morph systems technology opens a new view on sperm function. This is the first study applying this approach to evaluate different ejaculates and straws from the same individual. More work must be done to improve seminal dose calculations in assisted reproductive programs. PMID- 27678466 TI - Puma (Puma concolor) epididymal sperm morphometry. AB - The Andean puma (Puma concolor) has not been widely studied, particularly in reference to its semen characteristics. The aim of the present study was to define the morphometry of puma sperm heads and classify their subpopulations by cluster analysis. Samples were recovered postmortem from two epididymides from one animal and prepared for morphological observation after staining with the Hemacolor kit. Morphometric data were obtained from 581 spermatozoa using a CASA Morph system, rendering 13 morphometric parameters. The principal component (PC) analysis was performed followed by cluster analysis for the establishment of subpopulations. Two PC components were obtained, the first related to size and the second to shape. Three subpopulations were observed, corresponding to elongated and intermediate-size sperm heads and acrosomes, to large heads with large acrosomes, and to small heads with short acrosomes. In conclusion, puma spermatozoa showed no uniform sperm morphology but three clear subpopulations. These results should be used for future work in the establishment of an adequate germplasm bank of this species. PMID- 27678465 TI - Current status and potential of morphometric sperm analysis. AB - The spermatozoon is the most diverse cell type known and this diversity is considered to reflect differences in sperm function. How the diversity in sperm morphology arose during speciation and what role the different specializations play in sperm function, however, remain incompletely characterized. This work reviews the hypotheses proposed to explain sperm morphological evolution, with a focus on some aspects of sperm morphometric evaluation; the ability of morphometrics to predict sperm cryoresistance and male fertility is also discussed. For this, the evaluation of patterns of change of sperm head morphometry throughout a process, instead of the study of the morphometric characteristics of the sperm head at different stages, allows a better identification of the males with different sperm cryoconservation ability. These new approaches, together with more studies employing a greater number of individuals, are needed to obtain novel results concerning the role of sperm morphometry on sperm function. Future studies should aim at understanding the causes of sperm design diversity and the mechanisms that generate them, giving increased attention to other sperm structures besides the sperm head. The implementation of scientific and technological advances could benefit the simultaneous examination of sperm phenotype and sperm function, demonstrating that sperm morphometry could be a useful tool for sperm assessment. PMID- 27678468 TI - Reduced corporal fibrosis to protect erectile function by inhibiting the Rho kinase/LIM-kinase/cofilin pathway in the aged transgenic rat harboring human tissue kallikrein 1. AB - Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method. Masson's trichrome staining was used to evaluate corporal fibrosis in the corpus cavernosum. We found that the erectile function of rats in the aWTR group was significantly lower than that of other two groups. Masson's trichrome staining revealed that compared with those of the yWTR and aTGR groups, the ratio of smooth muscle cell (SMC)/collagen (C) was significantly lower in the aWTR group. Immunohistochemistry and Western blotting analysis were performed, and results demonstrated that expression of alpha-SMA was lower, while expressions of transforming growth factor-beta 1 (TGF-beta1), RhoA, ROCK1, p MYPT1, p-LIMK2, and p-cofilin were higher in the aWTR group compared with those in other two groups. However, LIMK2 and cofilin expressions did not differ among three groups. Taken together, these results indicated that the RhoA/ROCK1/LIMK/cofilin pathway may be involved in the corporal fibrosis caused by advanced age, and hKLK1 may reduce this corporal fibrosis by inhibiting the activation of this pathway to ameliorate age-related ED. PMID- 27678467 TI - Recent advances in bird sperm morphometric analysis and its role in male gamete characterization and reproduction technologies. AB - Postcopulatory sexual selection through sperm competition may be an important evolutionary force affecting many reproductive traits, including sperm morphometrics. Environmental factors such as pollutants, pesticides, and climate change may affect different sperm traits, and thus reproduction, in sensitive bird species. Many sperm-handling processes used in assisted reproductive techniques may also affect the size of sperm cells. The accurately measured dimensions of sperm cell structures (especially the head) can thus be used as indicators of environmental influences, in improving our understanding of reproductive and evolutionary strategies, and for optimizing assisted reproductive techniques (e.g., sperm cryopreservation) for use with birds. Computer-assisted sperm morphometry analysis (CASA-Morph) provides an accurate and reliable method for assessing sperm morphometry, reducing the problem of subjectivity associated with human visual assessment. Computerized systems have been standardized for use with semen from different mammalian species. Avian spermatozoa, however, are filiform, limiting their analysis with such systems, which were developed to examine the approximately spherical heads of mammalian sperm cells. To help overcome this, the standardization of staining techniques to be used in computer-assessed light microscopical methods is a priority. The present review discusses these points and describes the sperm morphometric characteristics of several wild and domestic bird species. PMID- 27678470 TI - Ring-shaped dysphotopsia associated with posterior chamber phakic implantable collamer lenses with a central hole. AB - PURPOSE: To evaluate the incidence of central hole-induced ring-shaped dysphotopsia after posterior chamber phakic implantable collamer lens (ICL) with central hole (hole ICL) implantation and to investigate the causes of central hole-induced dysphotopsia. METHODS: The clinical study enrolled 29 eyes of 15 consecutive myopic patients implanted with hole ICL. The incidence of ring-shaped dysphotopsia after hole ICL implantation was evaluated. In the experimental simulation study, non-sequential ray tracing was used to construct myopic human eye models with hole ICL and ICL without a central hole (conventional ICL). Simulated retinal images measured in log-scale irradiance were compared between the two ICLs for an extended Lambertian light-emitting disc object 20 cm in diameter placed 2 m from the corneal vertex. To investigate the causes of hole induced dysphotopsia, a series of retinal images were simulated using point sources at infinity with well-defined field angles (0 to -20 degrees ) and multiple ICL models. RESULTS: Of 29 eyes, 15 experienced ring-shaped dysphotopsia after hole ICL implantation. The simulation study using an extended Lambertian source showed that hole ICL-evoked ring-shaped dysphotopsia was formed at a retinal field angle of +/-40 degrees . Component-level analysis using a well defined off-axis point source from infinity revealed that ring-shaped dysphotopsia was generated by stray light refraction from the inner wall of the hole and the posterior ICL surface. CONCLUSION: Hole ICL-evoked ring-shaped dysphotopsia was related to light refraction at the central hole structure. Surgeons are advised to explain to patients the possibility of ring-shaped dysphotopsia after hole ICL implantation. PMID- 27678471 TI - Thirty years of investigation on the ergogenic effects of sodium citrate: is it time for a fresh start? AB - Sodium citrate (SCit) supplementation has been studied for several years as a strategy to reduce the muscle fatigue induced by H+ ion accumulation within the skeletal muscle during high-intensity, short-duration exercise. Several investigations have been published on this matter, and appear to indicate that SCit is not effective as an ergogenic aid, despite its ability to increase extracellular buffering capacity. In this short report, we briefly discuss the SCit results previously published in the literature and consider them in light of new and promising findings, which appear to address issues associated with previous study designs. We also suggest possible reasons for the current lack of reported ergogenic effects from this nutritional strategy and make recommendations that may re-define research in this area. PMID- 27678469 TI - The application of laparoscopic Doppler ultrasound during laparoscopic varicocelectomy in infertile men. AB - The aim of this study is to evaluate the benefits of laparoscopic Doppler ultrasound (LDU) application during laparoscopic varicocelectomy (LV), and to compare the surgical outcomes and complications between LDU-assisted LV (LDU-LV) and conventional LV for infertile patients with varicoceles; 147 infertile patients were randomly divided into two groups. Operative and postoperative parameters, semen parameters, and the pregnancy rate were compared. There were no differences in baseline demographics. The operative time was significantly longer in LDU-LV group than LV group. The incidence of postoperative hydrocele was 1.4% (1/72) in LDU-LV group versus 10.7% (8/75) in LV group, which showed a significant difference (P < 0.05). However, other surgical outcomes, such as postoperative hospital stay, postoperative recurrence, and testicular atrophy, were similar between the two groups. Sperm concentration and sperm motility were significantly increased in both groups at 3, 6, and 12 months after surgery (P < 0.01), and they were higher in LDU-LV than LV group in 12 months after surgery (34.21 +/- 6.36 vs 29.99 +/- 6.04 for concentration, P < 0.05; 40.72 +/- 8.12 vs 37.31 +/- 6.12 for motility, P < 0.05). Sperm morphology was comparable between the two groups. The pregnancy rate showed no significant difference (44.4% of the LDU-LV vs 37.3% of the LV, P > 0.05). In conclusion, compared with LV, LDU-LV could safely and effectively ligate all spermatic veins and preserve spermatic arteries without leading to high varicocele recurrence and postoperative hydrocele. Given the benefits that sperm counts as well as sperm motility favoring LDU-LV, we recommend that LDU should be routinely used as an effective tool to improve outcomes and safety of laparoscopic varicocelectomy. PMID- 27678472 TI - What are the Considerations in Balancing Benefits and Risks in Iron Treatment?: Emerging Evidence on the Safety of Intravenous Iron in Chronic Kidney Disease. PMID- 27678473 TI - In vivo and in vitro maturation of rabbit oocytes differently affects the gene expression profile, mitochondrial distribution, apoptosis and early embryo development. AB - In vivo-matured cumulus-oocyte complexes are valuable models in which to assess potential biomarkers of rabbit oocyte quality that contribute to enhanced IVM systems. In the present study we compared some gene markers of oocytes and cumulus cells (CCs) from immature, in vivo-matured and IVM oocytes. Moreover, apoptosis in CCs, nuclear maturation, mitochondrial reallocation and the developmental potential of oocytes after IVF were assessed. In relation to cumulus expansion, gene expression of gap junction protein, alpha 1, 43 kDa (Gja1) and prostaglandin-endoperoxide synthase 2 (Ptgs2) was significantly lower in CCs after in vivo maturation than IVM. In addition, there were differences in gene expression after in vivo maturation versus IVM in both oocytes and CCs for genes related to cell cycle regulation and apoptosis (V-Akt murine thymoma viral oncogene homologue 1 (Akt1), tumour protein 53 (Tp53), caspase 3, apoptosis related cysteine protease (Casp3)), oxidative response (superoxide dismutase 2, mitochondrial (Sod2)) and metabolism (glucose-6-phosphate dehydrogenase (G6pd), glyceraldehyde-3-phosphate dehydrogenase (Gapdh)). In vivo-matured CCs had a lower apoptosis rate than IVM and immature CCs. Meiotic progression, mitochondrial migration to the periphery and developmental competence were higher for in vivo-matured than IVM oocytes. In conclusion, differences in oocyte developmental capacity after IVM or in vivo maturation are accompanied by significant changes in transcript abundance in oocytes and their surrounding CCs, meiotic rate, mitochondrial distribution and apoptotic index. Some of the genes investigated, such as Gja1, could be potential biomarkers for oocyte developmental competence in the rabbit model, helping improve in vitro culture systems in these species. PMID- 27678474 TI - Identification of risk factors for moral distress in nurses: basis for the development of a new assessment tool. AB - This article proposes to identify risk factors for moral distress from the literature, validate them through expert analysis and provide the basis for a new tool to assess the risk of moral distress among nurses. Moral distress is related to the psychological, emotional and physiological aspects of nursing. It arises from constraints caused by various circumstances and can lead to significant negative consequences. A scoping review and validation through expert analysis were used. The research question guiding this study was as follows: What is known about risk factors for moral distress in nursing? The research was conducted using multiple sources including electronic databases and lists of references from relevant literature. The final sample consisted of 38 studies. A validation analysis was conducted by experts during December 2014 and June 2015. To exclude a risk factor item, at least 80% of the experts had to agree with the exclusion. In total, 53 risk factors for moral distress were identified, reviewed by the experts and grouped to form a new instrument that may help to identify risk for moral distress and to address its consequences. PMID- 27678475 TI - Influence of dosing times on cisplatin-induced peripheral neuropathy in rats. AB - BACKGROUND: Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. METHODS: CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. RESULTS: In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. CONCLUSIONS: It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy. PMID- 27678476 TI - Improving Polycyclic Aromatic Hydrocarbon Biodegradation in Contaminated Soil Through Low-Level Surfactant Addition After Conventional Bioremediation. AB - Efficacy of bioremediation for soil contaminated with polycyclic aromatic hydrocarbons (PAHs) may be limited by the fractions of soil-bound PAHs that are less accessible to PAH-degrading microorganisms. In previous test-tube-scale work, submicellar doses of nonionic surfactants were screened for their ability to enhance the desorption and biodegradation of residual PAHs in soil after conventional bioremediation in a laboratory-scale, slurry-phase bioreactor. Polyoxyethylene sorbitol hexaoleate (POESH) was the optimum surfactant for enhancing PAH removal, especially the high-molecular weight PAHs. This work extends that concept by treating the effluent from the slurry-phase bioreactor in a second-stage batch reactor, to which POESH was added, for an additional 7 or 12 days. Surfactant amendment removed substantial amounts of the PAHs and oxy-PAHs remaining after conventional slurry-phase bioremediation, including more than 80% of residual 4-ring PAHs. Surfactant-amended treatment decreased soil cytotoxicity, but often increased the genotoxicity of the soil as measured using the DT-40 chicken lymphocyte DNA damage response assay. Potential ecotoxicity, measured using a seed germination assay, was reduced by bioreactor treatment and was reduced further after second-stage treatment with POESH. Of bacteria previously implicated as potential PAH degraders under POESH-amended conditions in a prior study, members of the Terrimonas genus were associated with differences in high-molecular weight PAH removal in the current study. Research using submicellar doses of surfactant as a second-stage treatment step is limited and these findings can inform the design of bioremediation systems at field sites treating soil contaminated with PAHs and other hydrophobic contaminants that have low bioaccessibility. PMID- 27678477 TI - Particulate emissions from the combustion of birch, beech, and spruce logs cause different cytotoxic responses in A549 cells. AB - According to the World Health Organization particulate emissions from the combustion of solid fuels caused more than 110,000 premature deaths worldwide in 2010. Log wood combustion is the most prevalent form of residential biomass heating in developed countries, but it is unknown how the type of wood logs used in furnaces influences the chemical composition of the particulate emissions and their toxicological potential. We burned logs of birch, beech and spruce, which are used commonly as firewood in Central and Northern Europe in a modern masonry heater, and compared them to the particulate emissions from an automated pellet boiler fired with softwood pellets. We determined the chemical composition (elements, ions, and carbonaceous compounds) of the particulate emissions with a diameter of less than 1 um and tested their cytotoxicity, genotoxicity, inflammatory potential, and ability to induce oxidative stress in a human lung epithelial cell line. The chemical composition of the samples differed significantly, especially with regard to the carbonaceous and metal contents. Also the toxic effects in our tested endpoints varied considerably between each of the three log wood combustion samples, as well as between the log wood combustion samples and the pellet combustion sample. The difference in the toxicological potential of the samples in the various endpoints indicates the involvement of different pathways of toxicity depending on the chemical composition. All three emission samples from the log wood combustions were considerably more toxic in all endpoints than the emissions from the pellet combustion. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1487-1499, 2017. PMID- 27678478 TI - MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women. AB - Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. PMID- 27678479 TI - Improving prediction models with new markers: a comparison of updating strategies. AB - BACKGROUND: New markers hold the promise of improving risk prediction for individual patients. We aimed to compare the performance of different strategies to extend a previously developed prediction model with a new marker. METHODS: Our motivating example was the extension of a risk calculator for prostate cancer with a new marker that was available in a relatively small dataset. Performance of the strategies was also investigated in simulations. Development, marker and test sets with different sample sizes originating from the same underlying population were generated. A prediction model was fitted using logistic regression in the development set, extended using the marker set and validated in the test set. Extension strategies considered were re-estimating individual regression coefficients, updating of predictions using conditional likelihood ratios (LR) and imputation of marker values in the development set and subsequently fitting a model in the combined development and marker sets. Sample sizes considered for the development and marker set were 500 and 100, 500 and 500, and 100 and 500 patients. Discriminative ability of the extended models was quantified using the concordance statistic (c-statistic) and calibration was quantified using the calibration slope. RESULTS: All strategies led to extended models with increased discrimination (c-statistic increase from 0.75 to 0.80 in test sets). Strategies estimating a large number of parameters (re-estimation of all coefficients and updating using conditional LR) led to overfitting (calibration slope below 1). Parsimonious methods, limiting the number of coefficients to be re-estimated, or applying shrinkage after model revision, limited the amount of overfitting. Combining the development and marker set using imputation of missing marker values approach led to consistently good performing models in all scenarios. Similar results were observed in the motivating example. CONCLUSION: When the sample with the new marker information is small, parsimonious methods are required to prevent overfitting of a new prediction model. Combining all data with imputation of missing marker values is an attractive option, even if a relatively large marker data set is available. PMID- 27678480 TI - Seeing without knowing: Operational principles along the early visual pathway. AB - Single cases may lead to unexpected hypotheses in psychology. We retrospectively analyzed single case studies that suggested organizational principles along the early visual pathway, which have remained unanswered until now. FIRST CASE: In spite of the inhomogeneity of sensitivity, paradoxically the visual field on the subjective level appears to be homogeneous; constancy of brightness of supra threshold stimuli throughout the visual field is claimed to be responsible for homogeneity; specific summation properties of retinal ganglion cells are hypothesized to guarantee this effect. SECOND CASE: With a brain-injured patient having suffered a partial visual field loss it can be shown that color induction is a retinal phenomenon; lateral inhibitory processes at the level of amacrine cells are hypothesized as neural network. Third case: In a patient having suffered a bilateral occipital lobe infarction, some functional recovery has been demonstrated; divergence and convergence of projection in the ascending neural pathway are suggested as a structural basis for recovery. Slowed down binocular rivalry discloses a sequential mechanism in the construction of a visual percept. Fourth case: The pre-wired projection of the retina to the visual cortex in spite of a severe squint of one eye is confirmed, but paradoxically some local neuroplasticity is also suggested. Fifth case: Using habituation of local sensitivity in the visual field and its resetting by interhemispheric interactions as an experimental paradigm, it is suggested that spatial attention is controlled at the midbrain level. Sixth case: Observations on residual vision or "blindsight" support the hypothesis that the visual cortex is the one and only structure responsible for visual perception on a conscious level. The unifying principle of these retrospective analyses is that subjective visual phenomena can lead to unexpected but testable hypotheses of neural processing on the structural and functional level in the early visual pathway. PMID- 27678481 TI - Linking neuroimaging signals to behavioral responses in single cases: Challenges and opportunities. AB - Despite rapid progress both in psychology and neuroimaging, there is still a convergence gap between the results of these two scientific disciplines. This is particularly unsatisfactory, as the variability between single subjects needs to be understood both for basic science and for patient diagnostics in, for example, the field of age-related cognitive changes. Active and passive behaviors are the observables in psychology and can be studied alone or in combination with the neuroimaging approach. Various physical signatures of brain activity are the observables in neuroimaging and can be measured concurrent with behaviors. Despite the intrinsic relationship between behaviors and the corresponding neuroimaging patterns and the obvious advantages in integrating behavioral and neuroimaging measurements, the results of combined studies can be difficult to interpret. Experiments are often optimized to yield either a novel behavioral or a novel physiological result, but rarely designed for a better match between the two. Since integrating the results is probably a key to future progress in clinical psychology and basic research, an attempt is made here to identify some difficulties and to provide some ideas for future research. PMID- 27678482 TI - Scanning the world in three seconds: Mismatch negativity as an indicator of temporal segmentation. AB - It has been shown recently that a temporal window of approximately 3 s has a modulatory effect on mismatch negativity (MMN). This special temporal window has been interpreted as representing the "subjective present," and reflecting a temporal segmentation in behavioral and cognitive functions. A more detailed look into the temporal structure of the MMN appeared to be reasonable as group data might shadow the underlying mechanisms because of too-high response variance. In this study, we tested one subject on 11 successive days at the same circadian phase using a passive auditory oddball paradigm with interstimulus intervals (ISIs) ranging from 1 s to 6 s. We observed a U-shape function of MMN showing the largest amplitudes to the oddball stimuli with an ISI of 2 s and 3 s being flanked by smaller response amplitudes for shorter and longer ISIs. This result pattern can be explained with an oscillatory neural mechanism underlying the temporal modulation of MMN. Besides confirming and substantiating temporal segmentation in sensory processing, the present study also demonstrates that a single case study can be a useful and complementary tool in cognitive research. PMID- 27678483 TI - Donders revisited: Discrete or continuous temporal processing underlying reaction time distributions? AB - Differences of reaction times to specific stimulus configurations are used as indicators of cognitive processing stages. In this classical experimental paradigm, continuous temporal processing is implicitly assumed. Multimodal response distributions indicate, however, discrete time sampling, which is often masked by experimental conditions. Differences in reaction times reflect discrete temporal mechanisms that are pre-semantically implemented and suggested to be based on entrained neural oscillations. PMID- 27678484 TI - Microfluidics for mammalian embryo culture and selection: where do we stand now? AB - The optimization of in-vitro culture conditions and the selection of the embryo(s) with the highest developmental competence are essential components in an ART program. Culture conditions are manifold and they underlie not always evidence-based research but also trends entering the IVF laboratory. At the moment, the idea of using sequential media according to the embryo requirements has been given up in favor of the use of single step media in an uninterrupted manner due to practical issues such as time-lapse incubators. The selection of the best embryo is performed using morphological and, recently, also morphokinetic criteria. In this review, we aim to demonstrate how the ART field may benefit from the use of microfluidic technology, with a particular focus on specific steps, namely the embryo in-vitro culture, embryo scoring and selection, and embryo cryopreservation. We first provide an overview of microfluidic and microfabricated devices, which have been developed for embryo culture, characterization of pre-implantation embryos (or in some instances a combination of both steps) and embryo cryopreservation. Building upon these existing platforms and the various capabilities offered by microfluidics, we discuss how this technology could provide integrated and automated systems, not only for real time and multi-parametric monitoring of embryo development, but also for performing the entire ART procedure. Although microfluidic technology has been around for a couple of decades already, it has still not made its way into the clinics and IVF laboratories, which we discuss in terms of: (i) a lack of user friendliness and automation of the microfluidic platforms, (ii) a lack of robust and convincing validation using human embryos and (iii) some psychological threshold for embryologists and practitioners to test and use microfluidic technology. In spite of these limitations, we envision that microfluidics is likely to have a significant impact in the field of ART, for fundamental research in the near future and, in the longer term, for providing a novel generation of clinical tools. PMID- 27678485 TI - Uterosome-like vesicles prompt human sperm fertilizing capability. AB - STUDY QUESTION: Does the rapid transit through the uterine environment modulate the sperm physiological state? SUMMARY ANSWER: The uterosome-like vesicles (ULVs) secreted by endometrial epithelial cells (EECs) in vitro are able to fuse with human spermatozoa, prompting their fertilizing capacity. WHAT IS KNOWN ALREADY: Early studies suggest that sperm capacitation begins in the uterus and ends in the oviduct, and that a synergistic effect of both female organs may accelerate this process. Although it has been reported that co-incubation of human spermatozoa with endometrial cell-conditioned medium (CM) stimulates sperm capacitation, the mechanism mediating this communication is unknown. STUDY DESIGN, SIZE, DURATION: Human ULVs secreted by EECs were characterized and their effect on human sperm physiology was analysed. Spermatozoa were incubated with EEC-derived CM or ULV, after which sperm capacitation was evaluated at different time points. In addition, the interaction of spermatozoa with ULV was analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: ULVs were isolated by ultracentrifugation and identified using electron microscopy and Western blotting to assess the presence of specific protein markers. Following seminal plasma removal, human spermatozoa were incubated CM or ULV, after which sperm capacitation was evaluated as the ability of the sperm to undergo the induced acrosome reaction and the level of protein tyrosine phosphorylation (PY) determined by Western blot and immunocytochemistry. The interaction of spermatozoa with labelled ULV was analysed by fluorescence microscopy. In all cases, at least three biological replicates from different sperm donors were performed for each set of experiments. Significant differences between mean values were determined by one-way ANOVA followed by Tukey's post hoc test. Differences between treatments were considered statistically significant at P <= 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: The level of capacitated spermatozoa and those recruited by chemotaxis increased 3- to 4-fold when spermatozoa were incubated in the presence of CM for 4 h. Even a 15 min incubation of spermatozoa with CM was also enough to increase the level of capacitated cells 3- to 4-fold (P < 0.05). Furthermore, a short co-incubation of spermatozoa with ULV stimulates sperm capacitation, as determined by the increase in the level of induced acrosome reaction and the induction of PY. In addition, after the co-incubation of spermatozoa with fluorescent labelled ULV, the sperm cells acquired the fluorescent staining which indicates that ULV might be transferred to the sperm surface by a fusion mechanism. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study performed with human biological material, spermatozoa and endometrial derived cells; the latter being a cell line originally isolated from a uterine adenocarcinoma. WIDER IMPLICATIONS OF THE FINDINGS: The capability of spermatozoa to briefly interact with ULVs supports the hypothesis that any step of sperm transport may have physiological consequences, despite the interaction lasting for only a limited period of time. This way of communication of spermatozoa with cell products of uterine origin opens new frontiers of investigation (e.g. the signalling molecules involved), shedding light on the sperm processes that prepare the male gamete for fertilization, which might have implications for human infertility treatment. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTERESTS: The project was financially supported by SECyT-UNC. The authors declare no conflict of interest. PMID- 27678486 TI - Surgical repair of a ruptured sinus of Valsalva aneurysm in a patient with situs inversus totalis. PMID- 27678487 TI - Pex9p is a new yeast peroxisomal import receptor for PTS1-containing proteins. AB - Peroxisomal proteins carrying a type 1 peroxisomal targeting signal (PTS1) are recognized by the well-conserved cycling import receptor Pex5p. The yeast YMR018W gene encodes a Pex5p paralog and newly identified peroxin that is involved in peroxisomal import of a subset of matrix proteins. The new peroxin was designated Pex9p, and it interacts with the docking protein Pex14p and a subclass of PTS1 containing peroxisomal matrix enzymes. Unlike Pex5p, Pex9p is not expressed in glucose- or ethanol-grown cells, but it is strongly induced by oleate. Under these conditions, Pex9p acts as a cytosolic and membrane-bound peroxisome import receptor for both malate synthase isoenzymes, Mls1p and Mls2p. The inducible Pex9p-dependent import pathway provides a mechanism for the oleate-inducible peroxisomal targeting of malate synthases. The existence of two distinct PTS1 receptors, in addition to two PTS2-dependent import routes, contributes to the adaptive metabolic capacity of peroxisomes in response to environmental changes and underlines the role of peroxisomes as multi-purpose organelles. The identification of different import routes into peroxisomes contributes to the molecular understanding of how regulated protein targeting can alter the function of organelles according to cellular needs. PMID- 27678488 TI - Health-related quality of life of young people with long-term illnesses before and after transfer from child to adult healthcare. AB - BACKGROUND: The numbers of children with long-term illnesses surviving into adulthood and transferring from child to adult services has increased dramatically in the last 30 years. This study aimed to examine health-related quality of life pre- and post-transfer from child to adult healthcare for young people with three long-term illnesses. METHODS: A total of 217 young people with cystic fibrosis, congenital heart defects or diabetes attending child and adult hospital services in Dublin, Ireland completed a questionnaire survey. Multiple linear regression was used to identify predictors of five dimensions of health related quality of life pre- and post-transfer. RESULTS: Post-transfer young people with congenital heart disease and diabetes reported significantly lower physical well-being than their pre-transfer counterparts. Pre-transfer young people with cystic fibrosis reported significantly lower physical well-being than those with diabetes, but there was no significant difference post-transfer. Pre transfer females reported lower scores than males on the Psychological Well-being and Autonomy and Parent Relation dimensions; however, these differences disappeared post-transfer. Higher maternal overprotection scores were associated with significantly lower scores on the Psychological Well-being, Autonomy and Parent Relation, and Social Support and Peers dimensions, regardless of transfer status. CONCLUSIONS: Disease group, gender and maternal overprotection were predictors of health-related quality of life pre- and post-transfer from child to adult healthcare. Transition programmes should promote self-management and discourage parental overprotection. PMID- 27678489 TI - Alcohol promotions in Australian supermarket catalogues. AB - INTRODUCTION AND AIMS: In Australia, most alcohol is sold as packaged liquor from off-premises retailers, a market increasingly dominated by supermarket chains. Competition between retailers may encourage marketing approaches, for example, discounting, that evidence indicates contribute to alcohol-related harms. This research documented the nature and variety of promotional methods used by two major supermarket retailers to promote alcohol products in their supermarket catalogues. DESIGN AND METHODS: Weekly catalogues from the two largest Australian supermarket chains were reviewed for alcohol-related content over 12 months. Alcohol promotions were assessed for promotion type, product type, number of standard drinks, purchase price and price/standard drink. RESULTS: Each store catalogue included, on average, 13 alcohol promotions/week, with price-based promotions most common. Forty-five percent of promotions required the purchase of multiple alcohol items. Wine was the most frequently promoted product (44%), followed by beer (24%) and spirits (18%). Most (99%) wine cask (2-5 L container) promotions required multiple (two to three) casks to be purchased. The average number of standard drinks required to be purchased to participate in catalogue promotions was 31.7 (SD = 24.9; median = 23.1). The median price per standard drink was $1.49 (range $0.19-$9.81). Cask wines had the lowest cost per standard drink across all product types. DISCUSSION AND CONCLUSIONS: Supermarket catalogues' emphasis on low prices/high volumes of alcohol reflects that retailers are taking advantage of limited restrictions on off-premise sales and promotion, which allow them to approach market competition in ways that may increase alcohol-related harms in consumers. Regulation of alcohol marketing should address retailer catalogue promotions. [Johnston R, Stafford J, Pierce H, Daube M. Alcohol promotions in Australian supermarket catalogues. Drug Alcohol Rev 2017;36:456-463]. PMID- 27678490 TI - Ability emotional intelligence and its relation to aggression across time and age groups. AB - Emotional Intelligence (EI) has been associated with several indicators of psychosocial adjustment, including aggressive behavior, but the relevant research has been mostly cross-sectional, focused on adults, and limited to trait EI measures (Garcia-Sancho, Salguero & Fernandez-Berrocal, 2014; Mayer, Roberts & Barsade, ). The present work explored the relationship between Ability Emotional Intelligence (AEI) and aggression in both adults and adolescents using cross sectional and longitudinal designs. We conducted two studies. Study 1 aimed to provide preliminary evidence about the relationship between AEI and aggression in adults. As literature has shown personality traits act as a strong predictor of aggression, study 1 also examined the potential incremental validity of AEI beyond personality traits in 474 undergraduate students (M = 22.76, SD = 5.13). The results indicated AEI explains a significant amount of unique variance for physical aggression, but not for verbal aggression after controlling personality traits. Study 2 aimed a longitudinal analysis of the relationship between EI and aggression in 151 adolescents (M = 14.74, SD = 0.84). AEI predicted physical aggression over time, but it did not predict verbal aggression. Results from both studies suggest a negative and significant relationship between AEI and physical aggression, however contrary our expectations, it did not for verbal aggression. These results highlight the important explanatory role of emotional abilities in physical aggressive conducts and the implications of these findings are discussed. PMID- 27678491 TI - Evaluating Recall and Recognition Memory Using the Montreal Cognitive Assessment: Applicability for Alzheimer's and Huntington's Diseases. AB - We sought to investigate whether the Montreal Cognitive Assessment (MoCA) could provide a brief assessment of recall and recognition using Huntington disease (HD) and Alzheimer disease (AD) as disorders characterized by different memory deficits. This study included 80 participants with HD, 64 participants with AD, and 183 community-dwelling control participants. Random-effects hierarchical logistic regressions were performed to assess the relative performance of the normal control (NC), participants with HD, and participants with AD on verbal free recall, cued recall, and multiple-choice recognition on the MoCA. The NC participants performed significantly better than participants with AD at all the 3 levels of assessment. No difference existed between participants with HD and NC for cued recall, but NC participants performed significantly better than participants with HD on free recall and recognition. The participants with HD performed significantly better than participants with AD at all the 3 levels of assessment. The MoCA appears to be a valuable, brief cognitive assessment capable of identifying specific memory deficits consistent with known differences in memory profiles. PMID- 27678492 TI - Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation. AB - Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post-transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time-dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population. PMID- 27678493 TI - Aggregation-Induced Emission and Sensing Characteristics of Triarylborane Oligothiophene-Dicyanovinyl Triads. AB - The design, synthesis and aggregation-induced emission properties of a new series of triarylborane-oligothiophene-dicyanovinyl (DCV) conjugates 4-6 (A-D-A' type molecular configuration) are reported. The optical properties of 4-6 can be modulated by judiciously varying the number of thiophene units between electron deficient boryl and dicyanovinyl units. Compound 6 with terthiophene spacer showed highly red-shifted absorption and emission compared to 5 and 4 with bithiophene and monothiophene spacers, respectively. Compounds 5 and 6 show aggregation-induced emission enhancement in water/THF mixtures. Compounds 5 and 6 also showed solvent viscosity dependent emission characteristics. All the three compounds show distinct optical responses for small anions such as fluoride and cyanide. Filter paper strips coated with compounds 5 and 6 can detect F- and CN- in aqueous media with different colorimetric responses. PMID- 27678494 TI - Test-retest analysis of a non-invasive method of quantifying [(11)C]-PBR28 binding in Alzheimer's disease. AB - PURPOSE: In order to maximise the utility of [(11)C]-PBR28 for use in longitudinal studies and clinical trials in Alzheimer's disease (AD), there is a need to develop non-invasive metrics of tracer binding that do not require arterial cannulation. Recent work has suggested that standardised uptake value (SUV)-based methods may be sensitive to changes in translocator protein (TSPO) levels associated with neurodegeneration. However, the test-retest reliability of these approaches in AD over a time period relevant for clinical trials is unknown. In this study, the test-retest reliability of three SUV-based metrics was assessed in AD patients over 12 weeks. METHODS: Five patients with mild AD and the high-affinity binding TSPO genotype underwent two [(11)C]-PBR28 PET scans approximately 12 weeks apart. The test-retest reliability (TRR) of the unadjusted SUV, SUV relative to cerebellar grey matter (SUVRC) and SUV normalised to whole brain activity (SUVRWB) in nine cortical and limbic regions of interest was assessed using the absolute variability and the intraclass correlation coefficient. RESULTS: Of the three measures, SUVRWB performed best overall, showing low absolute variability (mean -0.13 %, SD 2.47 %) and high reliability (mean ICC = 0.83). Unadjusted SUV also performed well, with high reliability (ICC = 0.94) but also high variability (mean -1.24 %, SD 7.28 %). By comparison, the SUVRC showed higher variability (mean -3.98 %, SD 7.07 %) and low reliability (ICC = 0.65). CONCLUSIONS: In this AD sample, we found that SUV-derived metrics of [(11)C]-PBR28 binding showed high stability over 12 weeks. These results compare favourably with studies reporting TRR of absolute quantification of [(11)C]-PBR28. Pending further validation of SUV-based measures of [(11)C]-PBR28, semi-quantitative methods of [(11)C]-PBR28 analysis may prove useful in longitudinal studies of AD. PMID- 27678495 TI - Mechanically Robust and Transparent N-Halamine Grafted PVA-co-PE Films with Renewable Antimicrobial Activity. AB - Antimicrobial polymeric films that are both mechanically robust and function renewable would have broad technological implications for areas ranging from medical safety and bioengineering to foods industry; however, creating such materials has proven extremely challenging. Here, a novel strategy is reported to create high-strength N-halamine incorporated poly(vinyl alcohol-co-ethylene) films (HAF films) with renewable antimicrobial activity by combining melt radical graft polymerization and reactive extrusion technique. The approach allows here the intrinsically rechargeable N-halamine moieties to be covalently incorporated into polymeric films with high biocidal activity and durability. The resulting HAF films exhibit integrated properties of robust mechanical strength, high transparency, rechargeable chlorination capability (>300 ppm), and long-term durability, which can effectively offer 3-5 logs CFU reduction against typical pathogenic bacterium Escherichia coli within a short contact time of 1 h, even at high organism conditions. The successful synthesis of HAF films also provides a versatile platform for exploring the applications of antimicrobial N-halamine moieties in a self-supporting, structurally adaptive, and function renewable form. PMID- 27678496 TI - Inadvertent spinal injection of ondansetron. AB - Cesarean sections under spinal anesthesia are now a daily occurrence in most tertiary hospitals. We report the first published case of inadvertent spinal injection of ondansetron without any neurological sequelae in a patient undergoing elective Cesarean section under spinal anesthesia. She did not experience any permanent neurological sequelae, and also did not exhibit any central neuraxial opioid side effects-nausea, vomiting or pruritus. Vigilance is essential to reduce the risk of wrong route delivery of drugs, especially when presented in very similar-looking 2 mL ampules as in our institution. PMID- 27678497 TI - Possible association between successful intubation via the right nostril and anatomical variations of the nasopharynx during nasotracheal intubation: a multiplanar imaging study. AB - PURPOSE: Most reported cases of nasopharyngeal laceration following impingement during nasotracheal intubation involved tube insertion via the right nostril. We postulated that recesses on the posterior wall of the nasopharynx might be associated with tube impingement. Using multiplanar imaging and clinical statistics, we evaluated whether anatomical variations in the recesses are related to successful intubation via the right nostril. METHODS: Using multiplanar computed tomography (CT) images of 97 patients, we investigated the locations of recesses relative to the mid-sagittal plane, nasal floor plane and posterior end of the nasal septum, and their shapes. Incidents of impingement of the tube during nasotracheal intubation and the shapes of the fossa of Rosenmuller on CT images were retrospectively evaluated in 170 patients. RESULTS: Eustachian tube orifices were located approximately 10 mm laterally from the sagittal plane, and approximately 10 mm above the nasal floor plane. The fossa of Rosenmuller was vertically elongated and located 7 mm laterally from the mid sagittal plane. Pharyngeal bursae were found in 15 % of the subjects. Patients with failed insertion via the right nostril due to impingement frequently had a wide opening of the fossa of Rosenmuller. CONCLUSIONS: Successful intubation via the right nostril is related to the anatomy of structures on the posterior nasopharyngeal wall, particularly recesses located close to the path of nasotracheal tube insertion. Nasopharyngeal anatomical variations should be considered when one notices any resistance to advancement of the tube into the nasopharynx during nasotracheal intubation. PMID- 27678499 TI - Effects of soap-water wash on human epidermal penetration. PMID- 27678498 TI - Blood Pressure and Heart Rate Changes During Clozapine Treatment. AB - People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 +/- 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355 = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect. PMID- 27678501 TI - The promise of wearable sensors and ecological momentary assessment measures for dynamical systems modeling in adolescents: a feasibility and acceptability study. AB - Intervention development can be accelerated by using wearable sensors and ecological momentary assessment (EMA) to study how behaviors change within a person. The purpose of this study was to determine the feasibility and acceptability of a novel, intensive EMA method for assessing physiology, behavior, and psychosocial variables utilizing two objective sensors and a mobile application (app). Adolescents (n = 20) enrolled in a 20-day EMA protocol. Participants wore a physiological monitor and an accelerometer that measured sleep and physical activity and completed four surveys per day on an app. Participants provided approximately 81 % of the expected survey data. Participants were compliant to the wrist-worn accelerometer (75.3 %), which is a feasible measurement of physical activity/sleep (74.1 % complete data). The data capture (47.8 %) and compliance (70.28 %) with the physiological monitor were lower than other study variables. The findings support the use of an intensive assessment protocol to study real-time relationships between biopsychosocial variables and health behaviors. PMID- 27678502 TI - Effects of Neoadjuvant Chemotherapy Plus Radical Surgery as Front Line Treatment Strategy in Patients Affected by FIGO Stage III Cervical Cancer. AB - BACKGROUND: To assess the clinical efficacy and prognostic outcome of neoadjuvant chemotherapy (NACT) plus radical surgery (RS) as front line treatment in patients with FIGO stage III cervical cancer (CC). METHODS: In this retrospective study, 52 FIGO stage III CC patients treated from 2005 to 2015 were included. All patients received platinum-based chemotherapy. Patients reporting clinical response or stable disease after NACT underwent to RS and bilateral systematic pelvic lymphadenectomy with or without aortic lymphadenectomy or anterior exenteration. Patients with progressive disease underwent palliative management. RESULTS: After NACT, clinical response was observed in 23 patients (44 %): 4 (7.7 %) complete and 19 (36.5 %) partial responses, respectively. Also, 15 patients (28.8 %) had stable disease and 14 (26.9 %) showed disease progression. RS was performed in 40 cases (76.9 %): respectively, 28 (70 %) and 7 (17.5 %) underwent type C2 and D radical hysterectomy, while 5 patients (12.5 %) underwent anterior exenteration. At pathological evaluation, 23 patients (57.5 %) had positive pelvic nodes and 4 (10 %) also had positive aortic nodes. In 6 patients (15 %), moderate-severe (G3-G5) complications occurred. A total of 27 patients (67.5 %) received adjuvant therapy: 16 patients (40 %) received chemotherapy, 10 (25 %) received chemoradiation and 1 (2.5 %) received radiotherapy. Disease relapse occurred in 24 cases (60 %). After follow-up period of 60 months, the median OS of the whole population included was 37 months. Among the 40 surgically treated patients, median OS and DFS were 48 and 23 months, respectively. CONCLUSIONS: NACT plus RS represent a valid alternative with acceptable morbidity for patients with stage III CC. PMID- 27678500 TI - Applications and mechanisms of immunotherapy in allergic rhinitis and asthma. AB - Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-beta- producing T-regs and FoxP3+ T-regs. B-cell responses, including the induction of IL-10+ regulatory B-cells (B-regs) and the production of IgG4 associated blocking antibodies are also induced following successful AIT. These events are associated with the suppression of antigen-specific Th2 responses and delayed immune deviation in favour of Th1 type responses. Insight into the mechanisms of AIT has allowed identification of novel biomarkers with potential to predict the clinical response to AIT and also novel therapeutic strategies for more effective and safer AIT. PMID- 27678503 TI - Perioperative Hyperglycemia and Postoperative Outcomes in Patients Undergoing Resection of Colorectal Liver Metastases. AB - INTRODUCTION: There is limited evidence characterizing the impact of glycemic alterations on short-term outcomes among patients undergoing resection of colorectal liver metastases (CRLM). METHODS: Hyperglycemia was defined as a glucose value >125 mg/dl according to WHO definition. The impact of early postoperative hyperglycemia on short-term postoperative outcomes was assessed. RESULTS: The mean postoperative glucose value was 128 mg/dl; 30 (9.8 %) patients had normal fasting glucose (<100 mg/dl), 106 patients had glucose intolerance (100-125 mg/dl), and 170 (55.5 %) patients had hyperglycemia (>125 mg/dl). A postoperative complication occurred in 101 patients (morbidity, 33.1 %); among patients who experienced a complication, an infectious complication was most common (38.6 %). After controlling for clinical factors, patients with hyperglycemia had an increased risk of overall complications [odds ratio (OR) 4.11; 95 % confidence interval (CI) 1.96-8.62, P < 0.001]. This was the case for both patients with and without diabetes (P < 0.05). Patients with hyperglycemia on the day of surgery were also at an increased risk of infections [OR 9.17; 95 % CI 2.26-37.13, P = 0.002] and had a longer hospital stay (normal glucose, 4 days vs. glucose 100-125 mg/dl, 4 days vs. glucose >125 mg/dl, 5 days, P < 0.001). CONCLUSIONS: Early postoperative hyperglycemia was associated with adverse outcomes in patients with and without diabetes who underwent resection of CRLM. Perioperative glucose evaluation may be an important quality target. PMID- 27678504 TI - Cullin9 protects mouse eggs from aneuploidy by controlling microtubule dynamics via Survivin. AB - The Cullin9 gene encodes a putative E3 ligase that serves a wide variety of biological functions in mitosis, whereas its roles in meiosis have not yet clearly defined. Here, we report that Cullin9 accumulates on the spindle apparatus and colocalizes with the microtubule fibers during mouse oocyte meiotic maturation. Depletion of Cullin9 by morpholino microinjection results in a remarkably higher rate of disorganized spindles and misaligned chromosomes in oocytes, which is coupled with the impaired kinetochore-microtubule attachments. Resultantly, the incidence of aneuploid eggs significantly increases in Cullin9 depleted oocytes. Moreover, we show that Cullin9 controls Survivin's protein level during meiotic maturation, and thus regulates microtubule stability in oocytes. Thus, our study assigns a new meiotic function to Cullin9 and reveals that it prevents mouse eggs from aneuploidy by regulating microtubule dynamics via Survivin. PMID- 27678505 TI - HIV-Related Stigma Among Spanish-speaking Latinos in an Emerging Immigrant Receiving City. AB - HIV-related stigma has been associated with a reluctance to test for HIV among Latinos. This study assessed community HIV-related stigma within an emerging Latino immigrant receiving city. We conducted a brief survey among a convenience sample of 312 Spanish-speaking Latinos in Baltimore, Maryland. HIV-related stigma was assessed through six items. Associations between stigma items, socio demographic characteristics, and HIV testing history were considered. Gender, education, and religiosity were significantly associated with stigmatizing HIV related beliefs. For example, men were 3.4 times more likely to hold more than three stigmatizing beliefs than women, and were also twice as likely as women to report feeling hesitant to test for HIV for fear of people's reaction if the test is positive. These findings can help inform future stigma interventions in this community. In particular, we were able to distinguish between drivers of stigma such as fear and moralistic attitudes, highlighting specific actionable items. PMID- 27678506 TI - Gastric Electrical Stimulation for Gastroparesis and Chronic Unexplained Nausea and Vomiting. AB - OPINION STATEMENT: Gastroparesis is a heterogeneous clinical syndrome. Some patients have debilitating vomiting, weight loss, and dehydration, while others have effortless regurgitation of undigested foods or postprandial distress suggestive of functional dyspepsia. Gastric electrical stimulation (GES) has been proposed as an effective treatment option for patients with gastroparesis refractory to medical therapy. Evidence suggests that the clinically available device, a low-energy high-frequency GES, activates the vagal afferent pathways to influence the central control mechanisms for nausea and vomiting. Myoelectrical effects of the stomach are also involved. The results of randomized controlled trials (RCTs) for adults with diabetic and idiopathic gastroparesis are conflicting. There are no RCTs in adults with chronic unexplained nausea and vomiting (CUNV) with normal gastric emptying or in children with gastroparesis. However, there is increasing evidence from large unblinded studies showing the long-term efficacy in selected adults with gastroparesis. Selection criteria should be based on three categories: (a) underlying etiology, (b) clinical presentation and predominant symptoms, and (c) potential risk for complication. Significant abdominal pain, daily opiate use, and idiopathic gastroparesis are identified as negative predictors of success. Temporary GES has been utilized to identify patients who may benefit from surgical GES, but this strategy has yet to be proven in controlled studies. Objectives for this review are to highlight the mechanisms of action for GES, to look at the evidence for clinical efficacy, and to select patients who are likely to benefit. PMID- 27678507 TI - Infant gastrostomy outcomes: The cost of complications. AB - PURPOSE: Comparative outcomes of enhanced percutaneous endoscopic gastrostomy (PEG) and laparoscopic gastrostomy (LG) have not been elucidated in infants. We describe the outcomes and procedural episodic expenditures of PEG versus LG in this high-risk population. METHODS: One hundred eighty-three gastrostomies in children under 1year were reviewed from our institution spanning 1/2011-6/2015. Pertinent demographics and 3-month complications (mortality, gastrocolic fistula, reoperation, cellulitis, granulation, pneumonia, and tube dislodgement <6weeks) were collected. Facility and professional administrative data was used to conduct a charge and cost analysis of PEG and LG procedures as well as their statistically significant complications. RESULTS: Seventy-eight PEG and 105 LG infants were compared. LG infants were significantly younger, had higher ASA class, and increased frequency of cardiopulmonary disease. Significant major complications included a 3.8% incidence of gastrocolic fistula among PEGs (3.8% vs 0%, p=0.04) and 7.6% early tube dislodgements among LG infants (0 vs. 7.6%, p=0.01), resulting in $86,896 of additional charges with PEG complication. Incorporating complication frequency, average charges and variable cost per case were $8964 and $253 greater using PEG. CONCLUSIONS: Despite a healthier cohort, infants undergoing enhanced PEG have more morbid and costly complications. LG may be the less burdensome approach to gastrostomy in infants. LEVEL OF EVIDENCE: Case-Control Study/Retrospective Comparative Study - Level III. PMID- 27678508 TI - Hip stability during lengthening in children with congenital femoral deficiency. AB - BACKGROUND: Congenital femoral deficiency (CFD) is one of the most challenging and complex conditions for limb lengthening. We focused on the problem of hip instability during femoral lengthening because subluxation and dislocation are potentially catastrophic for hip function. METHODS: We assessed for hip stability in 69 children (91 femoral lengthenings) who had CFD Paley type 1a (43 children) and 1b (26 children). The mean age at first lengthening was 6.4 years. RESULTS: Hip subluxation/dislocation occurred during 14 (15 %) of 91 lengthenings. Thirty three pelvic osteotomies were performed before lengthening in an attempt to stabilize hips. Thirteen patients (type 1a, eight; type 1b, five) had acetabular dysplasia at initiation of lengthening. One of the eight with type 1a experienced mild femoral head subluxation; four of the five with type 1b experienced three dislocations and one subluxation. Eight patients (type 1b) experienced hip instability although they had pelvic osteotomies. Proximal femoral lengthening was a significant factor for hip subluxation. Patients with hip subluxation more likely underwent monolateral fixation and the original superhip procedure. Age +/ six years was not a contributing factor for hip instability. CONCLUSIONS: Important risk factors for hip instability during femoral lengthening are severity of CFD, residual acetabular dysplasia, and proximal femoral lengthening. We recommend routine performance of pelvic osteotomy for patients with Paley type 1b CFD and distal lengthening. LEVEL OF EVIDENCE: Therapeutic Level IV. PMID- 27678509 TI - Agaricus bisporus powder improved cutaneous mucosal and serum immune parameters and up-regulated intestinal cytokines gene expression in common carp (Cyprinus carpio) fingerlings. AB - The aim of the present study was to investigate immunomodulatory effects of Agaricus bisporus, white bottom mushroom powder (WBMP) on common carp (Cyprinus carpio) fingerlings. Carps were fed on different levels of WBMP (0, 0.5, 1 and 2%) for 8 weeks and at the end of feeding trial, skin mucus immune parameters (total Ig, lysozyme and protease activity), cytokines gene expression (TNF-alpha, IL1b, IL8) in intestine as well as serum non-specific immune parameters (total Ig, lysozyme and ACH50) were measured. The results showed significant dose dependent increase of skin mucus immune parameters in carps fed WBMP (P < 0.05). While, no significant difference was observed between 0.5% WBMP and control group (P > 0.05). In case of serum non-specific immune parameters, except lysozyme activity, other parameters (Ig total and ACH50) were significantly affected by dietary inclusion of WBMP (P < 0.05). Also, evaluation of cytokines gene expression in the intestine of carps revealed remarkable up-regulation of TNF alpha in fish fed 2% WBMP supplemented diet compared other treatment (P < 0.05). Likewise, IL1b gene expression was significantly increased in 1 and 2% WBMP treatments compared to the 0.5% WBMP and control groups (P < 0.05). IL8 gene expression was not affected by inclusion of WBMP in carp diet (P > 0.05). Furthermore, feeding on WBMP supplemented diet significantly improved growth performance (P < 0.05). These results indicated that WBMP can be considered as a promising immunostimulants in early stage of common carp culture. PMID- 27678510 TI - The cooperative expression of Heat Shock Protein 70 KD and 90 KD gene in juvenile Larimichthys crocea under Vibrio alginolyticus stress. AB - Heat shock proteins (HSPs) play significant roles in the immune response of fish in defending against diverse environmental threats or stresses. In this study, two complete HSP70 and HSP90 genes of Larimichthys crocea (designated as LycHSP70 and LycHSP90) were identified and characterized (GenBank accession no. KT456551 and KT456552). The complete open reading frame (ORF) fragments of LycHSP70 and LycHSP90 were 1917 bp and 2151 bp, encoding 638 and 716 amino acids residues respectively. Many significant functional domains and motifs were found, such as Hsp70 family signatures, Hsp90 family signatures, ATP-GTP binding site and EEVD motif regions, and they were associated with relative functions. Phylogenetic relationship and BLASTp analysis interpreted that they were unambiguously assigned to HSP70 and HSP90 family. The total length DNA of LycHSP70 was 7889bp, LycHSP90 was 5618 bp, and the gene location mapping were analyzed based on the whole-genomic DNA sequence of L. crocea. LycHSP70 and LycHSP90 were constantly expressed in eight tested tissues, with their expression peaks appearing in liver. Spleen, brain and head kidney also witnessed higher expression level. LycHSP70 and LycHSP90 were significantly induced by pathogenic bacteria V. alginolyticus, and they were both up-regulated in liver and spleen from 0 to 72 h post-injection. All the findings would contribute to better understanding the biologic function of HSPs in defending against pathogenic bacteria challenge and further exploring the innate immune response in fish. PMID- 27678512 TI - Spontaneous resolution of congenital anomalies of the kidney and the urinary tract (CAKUT). PMID- 27678511 TI - Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis. AB - : Less invasive surfactant therapies (LIST) use surfactant instillation through a thin tracheal catheter in spontaneously breathing infants. This review and meta analysis investigates respiratory outcomes for preterm infants with respiratory distress syndrome treated with LIST rather than administration of surfactant through an endotracheal tube. Randomised controlled trial (RCT) full texts provided outcome data for bronchopulmonary dysplasia (BPD), death or BPD, early CPAP failure, invasive ventilation requirements and usual neonatal morbidities. Relative risks (RR) from pooled data, with subgroup analyses, were obtained from a Mantel-Haenszel analysis using a random effect model. Six RCTs evaluated LIST: 4 vs InSurE and 1 each vs delayed or immediate intubation for surfactant. LIST resulted in decreased risks of BPD (RR = 0.71 [0.52-0.99]; NNT = 21), death or BPD (RR = 0.74 [0.58-0.94]; NNT = 15) and early CPAP failure or invasive ventilation requirements (RR = 0.67 [0.53-0.84]; NNT = 8 and RR = 0.69 [0.53 0.88]; NNT = 6). Compared to InSurE, LIST decreased the risks of BPD or death (RR = 0.63 [0.44-0.92]; NNT = 11) and of early CPAP failure (RR = 0.71 [0.53-0.96]; NNT = 11). Common neonatal morbidities were not different. CONCLUSIONS: Respiratory management with LIST decreases the risks of BPD and BPD or death, and the need for invasive ventilation. This strategy appears safe, but long-term follow-up is lacking. What is Known: * Initial management of preterm infants with CPAP decreases the risk of death or BPD, but many still require surfactant or invasive ventilation. * Surfactant can be instilled through a tracheal thin catheter while the infant breathes on CPAP, but improvement in BPD is inconsistent between studies. What is New: * Less invasive surfactant therapy (LIST) strategies decrease the risks of BPD, of death or BPD, and of CPAP failure compared to strategies where surfactant is administered through an endotracheal tube. * LIST strategies decrease the risks of the composite outcome of BPD or death and of early CPAP failure when compared to "intubation-surfactant extubation" approaches. PMID- 27678513 TI - Determinants of coronary blood flow in sandbar sharks, Carcharhinus plumbeus. AB - The coronary circulation first appeared in the chordate lineage in cartilaginous fishes where, as in birds and mammals but unlike most teleost fishes, it supplies arterial blood to the entire myocardium. Despite the pivotal position of elasmobranch fishes in the evolution of the coronary circulation, the determinants of coronary blood flow have never been investigated in this group. Elasmobranch fishes are of special interest because of the morphological arrangement of their cardiomyocytes. Unlike teleosts, the majority of the ventricular myocardium in elasmobranch fishes is distant to the venous blood returning to the heart (i.e., the luminal blood). Also, the majority of the myocardium is in close association with the coronary circulation. To determine the relative contribution of the coronary and luminal blood supplies to cardiovascular function in sandbar sharks, Carcharhinus plumbeus, we measured coronary blood flow while manipulating cardiovascular status using acetylcholine and adrenaline. By exploring inter- and intra-individual variation in cardiovascular variables, we show that coronary blood flow is directly related to heart rate (R 2 = 0.6; P < 0.001), as it is in mammalian hearts. Since coronary blood flow is inversely related to coronary resistance both in vivo and in vitro, we suggest that in elasmobranch fishes, changes in heart rate mediate changes in coronary vascular resistance, which adjust coronary blood flow appropriately. PMID- 27678514 TI - Fifteen minutes of daily contact with sexually active male induces ovulation but delays its timing in seasonally anestrous goats. AB - The present experiment was conducted to determine (1) whether the sexually active bucks are able to stimulate the ovulatory activity of seasonal anestrous goats when the daily contact is reduced to 15 min/day during 15 days and (2) the exact ovulatory activity in anestrous goats exposed to bucks for 2 hours or less per day during 15 days. One group of goats (n = 15) was isolated from bucks. The other six groups (n = 15 each) were exposed to sexually active bucks (n = 1 each) for 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, or 24 hours during 15 days. Goats with plasma concentrations of progesterone greater than 0.5 ng/mL were considered to have ovulated. More than 93% of females exposed to bucks ovulated throughout the experiment regardless of the duration of contact with males, whereas none of them ovulated in the isolated group (P < 0.0001). The proportions of females that ovulated at least once did not differ among groups as well as the proportions of goats that displayed normal or short ovulatory cycles. The interval between the introduction of males and the first ovulation did not differ among groups of goats in contact with bucks for 15 minutes, 30 minutes, 1 hour, or 2 hours. However, in these groups, this ovulation occurred about 2 days later than in females in contact with males during 4 or 24 hours (6.3 vs. 4.4 days; P < 0.05). We conclude that 15 minutes of daily contact with sexually active buck is sufficient to stimulate the ovulatory activity in seasonally anestrous goats, but the first ovulation is delayed in goats exposed to males for 2 h/day or less during 15 days in comparison with those in contact with males for 4 or 24 h/day. PMID- 27678516 TI - Medical-legal assessments - the educational implications, working with educational psychologists. PMID- 27678515 TI - Relationship between in vitro sperm functional assessments, seminal plasma composition, and field fertility after AI with either non-sorted or sex-sorted bull semen. AB - The hypothesis of this study was that different in vitro parameters are required to predict the in vivo fertility of non-sorted (NS) and sex-sorted (SS) semen. Thus, the aim was to correlate in vitro bull sperm functional parameters (experiment 1) and seminal plasma composition (experiment 2) with pregnancy rates using 2 cohorts of bulls (NS and SS). Experiment 1: ejaculates from each bull (n = 3 ejaculates per bull; n = 6 bulls for both NS and SS) were assessed for motility, thermal stress tolerance and morphology using microscopy, and viability, osmotic resistance, mitochondrial membrane potential, and acrosome integrity using flow cytometry. Fertilizing ability was assessed using IVF. Experiment 2: ejaculates (n = 3 per bull; n = 8 and 6 bulls for NS and SS, respectively) were collected, seminal plasma harvested and frozen and later analyzed for amino acid and fatty acid composition using gas chromatography mass spectrometry. In the NS cohort of bulls, there was no correlation between pregnancy rate and any of the sperm functional parameters assessed. However, within the SS cohort, motility and viability were correlated with pregnancy rate (r = 0.84 and 0.80, respectively; P < 0.05). There was no correlation between IVF outcome and pregnancy rate in either the SS or NS cohort of bulls. In the NS cohort of bulls, concentrations of the amino acid isoleucine and the fatty acid tricosylic acid (C23:0) were correlated with pregnancy rate (r = 0.80 and 0.74, respectively; P < 0.05). Within the SS cohort of bulls, the amino acid glutamic acid and the fatty acid arachidic acid (C20:0) were correlated with pregnancy rate (r = 0.84 and 0.82, respectively; P < 0.05). In conclusion, this study suggests that different in vitro markers of fertility are required to predict the fertility of NS and SS sperm. PMID- 27678517 TI - Loperamide-related deaths in North Carolina. PMID- 27678518 TI - A Natural Mutation Involving both Pathogenicity and Perithecium Formation in the Fusarium graminearum Species Complex. AB - Members of the Fusarium graminearum species complex (Fg complex or FGSC) are the primary pathogens causing Fusarium head blight in wheat and barley worldwide. A natural pathogenicity mutant (strain 0225022) was found in a sample of the Fg complex collected in Japan. The mutant strain did not induce symptoms in wheat spikes beyond the point of inoculation, and did not form perithecia. No segregation of phenotypic deficiencies occurred in the progenies of a cross between the mutant and a fully pathogenic wild-type strain, which suggested that a single genetic locus controlled both traits. The locus was mapped to chromosome 2 by using sequence-tagged markers; and a deletion of ~3 kb was detected in the mapped region of the mutant strain. The wild-type strain contains the FGSG_02810 gene, encoding a putative glycosylphosphatidylinositol anchor protein, in this region. The contribution of FGSG_02810 to pathogenicity and perithecium formation was confirmed by complementation in the mutant strain using gene transfer, and by gene disruption in the wild-type strain. PMID- 27678519 TI - Autosomal and X-Linked Additive Genetic Variation for Lifespan and Aging: Comparisons Within and Between the Sexes in Drosophila melanogaster. AB - Theory makes several predictions concerning differences in genetic variation between the X chromosome and the autosomes due to male X hemizygosity. The X chromosome should: (i) typically show relatively less standing genetic variation than the autosomes, (ii) exhibit more variation in males compared to females because of dosage compensation, and (iii) potentially be enriched with sex specific genetic variation. Here, we address each of these predictions for lifespan and aging in Drosophila melanogaster To achieve unbiased estimates of X and autosomal additive genetic variance, we use 80 chromosome substitution lines; 40 for the X chromosome and 40 combining the two major autosomes, which we assay for sex-specific and cross-sex genetic (co)variation. We find significant X and autosomal additive genetic variance for both traits in both sexes (with reservation for X-linked variation of aging in females), but no conclusive evidence for depletion of X-linked variation (measured through females). Males display more X-linked variation for lifespan than females, but it is unclear if this is due to dosage compensation since also autosomal variation is larger in males. Finally, our results suggest that the X chromosome is enriched for sex specific genetic variation in lifespan but results were less conclusive for aging overall. Collectively, these results suggest that the X chromosome has reduced capacity to respond to sexually concordant selection on lifespan from standing genetic variation, while its ability to respond to sexually antagonistic selection may be augmented. PMID- 27678520 TI - Drosophila CG2469 Encodes a Homolog of Human CTR9 and Is Essential for Development. AB - Conserved from yeast to humans, the Paf1 complex participates in a number of diverse processes including transcriptional initiation and polyadenylation. This complex typically includes five proteins: Paf1, Rtf1, Cdc73, Leo1, and Ctr9. Previous efforts identified clear Drosophila homologs of Paf1, Rtf1, and Cdc73 based on sequence similarity. Further work showed that these proteins help to regulate gene expression and are required for viability. To date, a Drosophila homolog of Ctr9 has remained uncharacterized. Here, we show that the gene CG2469 encodes a functional Drosophila Ctr9 homolog. Both human and Drosophila Ctr9 localize to the nuclei of Drosophila cells and appear enriched in histone locus bodies. RNAi knockdown of Drosophila Ctr9 results in a germline stem cell loss phenotype marked by defects in the morphology of germ cell nuclei. A molecular null mutation of Drosophila Ctr9 results in lethality and a human cDNA CTR9 transgene rescues this phenotype. Clonal analysis in the ovary using this null allele reveals that loss of Drosophila Ctr9 results in a reduction of global levels of histone H3 trimethylation of lysine 4 (H3K4me3), but does not compromise the maintenance of stem cells in ovaries. Given the differences between the null mutant and RNAi knockdown phenotypes, the germ cell defects caused by RNAi likely result from the combined loss of Drosophila Ctr9 and other unidentified genes. These data provide further evidence that the function of this Paf1 complex component is conserved across species. PMID- 27678522 TI - On Robust Association Testing for Quantitative Traits and Rare Variants. AB - With the advance of sequencing technologies, it has become a routine practice to test for association between a quantitative trait and a set of rare variants (RVs). While a number of RV association tests have been proposed, there is a dearth of studies on the robustness of RV association testing for nonnormal distributed traits, e.g., due to skewness, which is ubiquitous in cohort studies. By extensive simulations, we demonstrate that commonly used RV tests, including sequence kernel association test (SKAT) and optimal unified SKAT (SKAT-O), are not robust to heavy-tailed or right-skewed trait distributions with inflated type I error rates; in contrast, the adaptive sum of powered score (aSPU) test is much more robust. Here we further propose a robust version of the aSPU test, called aSPUr. We conduct extensive simulations to evaluate the power of the tests, finding that for a larger number of RVs, aSPU is often more powerful than SKAT and SKAT-O, owing to its high data-adaptivity. We also compare different tests by conducting association analysis of triglyceride levels using the NHLBI ESP whole exome sequencing data. The QQ plots for SKAT and SKAT-O were severely inflated (lambda = 1.89 and 1.78, respectively), while those for aSPU and aSPUr behaved normally. Due to its relatively high robustness to outliers and high power of the aSPU test, we recommend its use complementary to SKAT and SKAT-O. If there is evidence of inflated type I error rate from the aSPU test, we would recommend the use of the more robust, but less powerful, aSPUr test. PMID- 27678524 TI - A microtubule inhibitor, ABT-751, induces autophagy and delays apoptosis in Huh-7 cells. AB - The objective was to investigate the upstream mechanisms of apoptosis which were triggered by a novel anti-microtubule drug, ABT-751, in hepatocellular carcinoma derived Huh-7 cells. Effects of ABT-751 were evaluated by immunocytochemistry, flow cytometric, alkaline comet, soft agar, immunoblotting, CytoID, green fluorescent protein-microtubule associated protein 1 light chain 3 beta detection, plasmid transfection, nuclear/cytosol fractionation, coimmunoprecipitation, quantitative reverse transcription-polymerase chain reaction, small-hairpin RNA interference and mitochondria/cytosol fractionation assays. Results showed that ABT-751 caused dysregulation of microtubule, collapse of mitochondrial membrane potential, generation of reactive oxygen species (ROS), DNA damage, G2/M cell cycle arrest, inhibition of anchorage-independent cell growth and apoptosis in Huh-7 cells. ABT-751 also induced early autophagy via upregulation of nuclear TP53 and downregulation of the AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin (MTOR) pathway. Through modulation of the expression levels of DNA damage checkpoint proteins and G2/M cell cycle regulators, ABT-751 induced G2/M cell cycle arrest. Subsequently, ABT-751 triggered apoptosis with marked downregulation of B-cell CLL/lymphoma 2, upregulation of mitochondrial BCL2 antagonist/killer 1 and BCL2 like 11 protein levels, and cleavages of caspase 8 (CASP8), CASP9, CASP3 and DNA fragmentation factor subunit alpha proteins. Suppression of ROS significantly decreased ABT-751 induced autophagic and apoptotic cells. Pharmacological inhibition of autophagy significantly increased the percentages of ABT-751-induced apoptotic cells. The autophagy induced by ABT-751 plays a protective role to postpone apoptosis by exerting adaptive responses following microtubule damage, ROS and/or impaired mitochondria. PMID- 27678521 TI - Prevention of DNA Rereplication Through a Meiotic Recombination Checkpoint Response. AB - In the budding yeast Saccharomyces cerevisiae, unnatural stabilization of the cyclin-dependent kinase inhibitor Sic1 during meiosis can trigger extra rounds of DNA replication. When programmed DNA double-strand breaks (DSBs) are generated but not repaired due to absence of DMC1, a pathway involving the checkpoint gene RAD17 prevents this DNA rereplication. Further genetic analysis has now revealed that prevention of DNA rereplication also requires MEC1, which encodes a protein kinase that serves as a central checkpoint regulator in several pathways including the meiotic recombination checkpoint response. Downstream of MEC1, MEK1 is required through its function to inhibit repair between sister chromatids. By contrast, meiotic recombination checkpoint effectors that regulate gene expression and cyclin-dependent kinase activity are not necessary. Phosphorylation of histone H2A, which is catalyzed by Mec1 and the related Tel1 protein kinase in response to DSBs, and can help coordinate activation of the Rad53 checkpoint protein kinase in the mitotic cell cycle, is required for the full checkpoint response. Phosphorylation sites that are targeted by Rad53 in a mitotic S phase checkpoint response are also involved, based on the behavior of cells containing mutations in the DBF4 and SLD3 DNA replication genes. However, RAD53 does not appear to be required, nor does RAD9, which encodes a mediator of Rad53, consistent with their lack of function in the recombination checkpoint pathway that prevents meiotic progression. While this response is similar to a checkpoint mechanism that inhibits initiation of DNA replication in the mitotic cell cycle, the evidence points to a new variation on DNA replication control. PMID- 27678523 TI - X Chromosome Crossover Formation and Genome Stability in Caenorhabditis elegans Are Independently Regulated by xnd-1. AB - The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs, and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover (CO) distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understood. We have used the xnd-1 mutant of Caenorhabditis elegans to explore the relationship between genome integrity and crossover formation. Known for its role in ensuring X chromosome CO formation and germ line development, we show that xnd-1 also regulates genome stability. xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of mys-1 suppressed these genome instability phenotypes of xnd-1, but did not suppress the CO defects, suggesting it serves as a separation-of-function allele. mys-1 encodes a histone acetyltransferase, whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in xnd-1 mutant germ lines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that xnd-1 regulated him-5 transcriptionally, independently of mys-1, and that ectopic expression of him-5 suppressed the CO defects of xnd-1 Our work provides xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability. PMID- 27678525 TI - Defining Ocular Surface Disease Activity and Damage Indices by an International Delphi Consultation. AB - PURPOSE: Unifying terminology for the description of ocular surface disease (OSD) is vital for determining treatment responses and ensuring robust clinical trial outcomes. To date, there are no agreed parameters describing 'activity' and 'damage' phases of disease. METHODS: A working group of international experts in OSD, oculoplastics, and uveitis from a range of backgrounds (university, teaching, district general and private hospitals) participated in a modified Delphi consensus-building exercise (October 31, 2011 to March 20, 2015). Two steering group meetings took place in which factors based upon published literature were discussed and supplemented with anonymous web-based questionnaires to refine clinical indices according to 'activity' (reversible changes resulting directly from the inflammatory process) and/or 'damage' (persistent, >6 months duration) changes resulting from previously active disease that are cumulative and irreversible). RESULTS: The recommended set of clinical parameters for the assessment of OSD encompasses 68 clinical indices and 22 ancillary grading tools (in parenthesis) subdivided by anatomical domain as follows: 4(4) tear-film, eyelid 21(3), 17(3) conjunctiva, 15(10) cornea and 11(2) Anterior Chamber/Sclera. Of these; 17(2) were considered as measures of clinical activity, 27(3) as damage, 1(8) as measures of both activity and damage. Twenty three clinical descriptors and 9 tools did not reach the threshold for inclusion into the main standard set. These were defined as 'second tier' parameters for use in special clinical settings. CONCLUSION: These core parameters provide the first description of 'activity' and 'damage' relevant to OSD and provide a platform for the future development of scoring scales for each parameter. PMID- 27678526 TI - Large-scale monitoring of effects of clothianidin-dressed OSR seeds on pollinating insects in Northern Germany: effects on large earth bumble bees (Bombus terrestris). AB - The aim of this study was to investigate the effects of Elado(r)-dressed winter oilseed rape (OSR, 10 g clothianidin & 2 g beta-cyfluthrin/kg seed) on the development, reproduction and behaviour of large earth bumble bees (Bombus terrestris) as part of a large-scale monitoring field study in Northern Germany, where OSR is usually cultivated at 25-33 % of the arable land. Both reference and test sites comprised 65 km2 in which no other crops attractive to pollinating insects were present. Six study locations were selected per site and 10 bumble bee hives were placed at each location. At each site, three locations were directly adjacent to OSR fields and three locations were situated 400 m distant from the nearest OSR field. The development of colonies was monitored from the beginning of OSR flowering in April until June 2014. Pollen from returning foragers was analysed for its composition. An average of 44 % of OSR pollen was found in pollen loads of bumble bees indicating that OSR was a major resource for the colonies. At the end of OSR flowering, hives were transferred to a nature reserve until the end of the study. Colony development in terms of hive weight and the number of workers showed a typical course with no statistically significant differences between the sites. Reproductive output was comparatively high and not negatively affected by the exposure to treated OSR. In summary, Elado(r)-dressed OSR did not cause any detrimental effects on the development or reproduction of bumble bee colonies. PMID- 27678527 TI - Large-scale monitoring of effects of clothianidin dressed oilseed rape seeds on pollinating insects in Northern Germany: implementation of the monitoring project and its representativeness. AB - Monitoring studies at the landscape level are complex, expensive and difficult to conduct. Many aspects have to be considered to avoid confounding effects which is probably the reason why they are not regularly performed in the context of risk assessments of plant protection products to pollinating insects. However, if conducted appropriately their contribution is most valuable. In this paper we identify the requirements of a large-scale monitoring study for the assessment of side-effects of clothianidin seed-treated winter oilseed rape on three species of pollinating insects (Apis mellifera, Bombus terrestris and Osmia bicornis) and present how these requirements were implemented. Two circular study sites were delineated next to each other in northeast Germany and comprised almost 65 km2 each. At the reference site, study fields were drilled with clothianidin-free OSR seeds while at the test site the oilseed rape seeds contained a coating with 10 g clothianidin and 2 g beta-cyfluthrin per kg seeds (Elado(r)). The comparison of environmental conditions at the study sites indicated that they are as similar as possible in terms of climate, soil, land use, history and current practice of agriculture as well as in availability of oilseed rape and non-crop bee forage. Accordingly, local environmental conditions were considered not to have had any confounding effect on the results of the monitoring of the bee species. Furthermore, the study area was found to be representative for other oilseed rape cultivation regions in Europe. PMID- 27678528 TI - FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process. AB - Fibroblast growth factor 21 (FGF21) has a significant role in the regulation of energy metabolism, e.g., in the control of systemic glucose and lipid metabolism. For instance, FGF21 enhances insulin sensitivity, increases glucose uptake, and thus can decrease serum hyperglycemia, while it also increases lipid oxidation and inhibits lipogenesis. AMP-activated protein kinase (AMPK) is a tissue energy sensor involved in maintaining the energy balance and tissue integrity. It is known that AMPK signaling generates an energy metabolic profile which displays a remarkable overlap with that of FGF21. There is convincing evidence that endocrine FGF21 signaling activates the AMPK pathway, either directly through FGFR1/beta-klotho signaling or indirectly by stimulating the secretion of adiponectin and corticosteroids, which consequently can activate AMPK signaling in their target tissues. By activating AMPK, FGF21 can promote a healthy aging process and thus extend mammalian lifespan. We will examine the signaling mechanisms through which FGF21 can activate the AMPK pathway and then discuss the significance of the close connection between FGF21 and AMPK signaling in the control of metabolic disorders and the aging process. PMID- 27678530 TI - Early real-world evidence of persistence on oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a cohort study in UK primary care. AB - OBJECTIVES: To examine the characteristics and persistence in patients newly initiated with oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). DESIGN: Cohort study in Clinical Practice Research Datalink. SETTING: UK primary care. PARTICIPANTS: 15 242 patients with NVAF newly prescribed apixaban, rivaroxaban, dabigatran or vitamin K antagonists (VKAs) between 1 December 2012 and 31 October 2014. 13 089 patients were OAC naive. OUTCOME MEASURES: Patient characteristics and risk of non-persistence compared to apixaban using Cox regression models over the entire follow-up and using a time partitioned approach to handle non-proportional hazards. RESULTS: Among the OAC naive patients, VKAs were most common (78.1%, n=10 218), followed by rivaroxaban (12.1%, n=1589), dabigatran (5.7%, n=741) and apixaban (4.1%, n=541). High baseline stroke risk (CHA2DS2VASc >=2) ranged from 80.2% (dabigatran) to 88.4% (apixaban and rivaroxaban). History of stroke and bleeding was the highest among apixaban (23.7% and 31.6%) and lowest among VKA patients (15.9% and 27.5%). Across the entire follow-up period, adjusting for differences in characteristics, there was no evidence of a difference in non-persistence between VKA and apixaban (HR 0.92 (95% CI 0.68 to 1.23)). Non-persistence was higher with dabigatran (HR 1.67 (1.20 to 2.32)) and rivaroxaban (HR 1.41 (1.02 to 1.93)) than apixaban. Using the partitioned approach, non-persistence was lower with VKA (HR 0.33 (0.22 to 0.48)), and higher with dabigatran (HR 1.65 (1.08 to 2.52)) compared to apixaban in the first 2 months of follow-up. After 2 months, non-persistence was higher with VKA (HR 1.70 (1.08 to 2.66)) and dabigatran (HR 2.10 (1.30 to 3.41)). Pooling OAC naive and experienced patients, non-persistence was also higher with rivaroxaban compared to apixaban after 2 months of follow-up (HR 1.69 (1.19 to 2.39)). CONCLUSIONS: Observed differential prescribing of OACs can result in channelling bias in comparative effectiveness research. Persistence patterns changed over follow-up time, but there are indications of improved persistence rates with apixaban over other OACs in the UK. A larger study with longer follow up is needed to corroborate findings. This study is registered on ClinicalTrials.gov (NCT02488421). PMID- 27678531 TI - Qualitative study of the clinician-parent interface in discussing prognosis following MRI and US imaging of preterm infants in the UK. AB - OBJECTIVE: To explore communication and interaction between parents and clinicians following neonatal ultrasound (US) and MRI of the brain of babies born preterm. SETTING: This qualitative study was undertaken as part of a larger UK study of neonatal brain imaging. 511 infants were cared for in 14 London neonatal units with MR and cerebral US imaging in a specialist centre. PARTICIPANTS: Parents with infants born at <33 weeks gestation were randomised to receive prognostic information based on either MRI or US findings on their infants at term-corrected age. METHODS: Discussions between parents and clinicians about the MRI or US result were audio recorded. Parents were told about the findings and their baby's predicted outcome. A topic guide ensured essential aspects were covered. Recordings were fully transcribed. Discussion of the scan results, the content and style of the interaction and parental response were analysed qualitatively in 36 recordings using NVivo V.10. OUTCOMES: Key themes and subthemes were identified in the clinician-parent discussions. RESULTS: The overarching theme of 'the communication interface' was identified with three key themes: 'giving information', 'managing the conversation' and 'getting it right' and further subthemes. A range of approaches were used to facilitate parental understanding and engagement. There were differences in the exchanges when information about an abnormal scan was given. The overall structure of the discussions was largely similar, though the language used varied. In all of the discussions, the clinicians talked more than the parents. CONCLUSIONS: The discussions represent a difficult situation in which the challenge is to give and receive complex prognostic information in the context of considerable uncertainty. The study highlights the importance of being able to re-visit specific issues and any potential areas of misunderstanding, of making time to talk to parents appreciating their perspective and level of knowledge. TRIAL REGISTRATION NUMBER: EudraCT 2009-013888-19; Pre-results. PMID- 27678529 TI - Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus. AB - Autoinflammatory disorders are sterile inflammatory conditions characterized by episodes of early-onset fever and disease-specific patterns of organ inflammation. Recently, the discoveries of monogenic disorders with strong type I interferon (IFN) signatures caused by mutations in proteasome degradation and cytoplasmic RNA and DNA sensing pathways suggest a pathogenic role of IFNs in causing autoinflammatory phenotypes. The IFN response gene signature (IGS) has been associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. In this review, we compare the clinical presentations and pathogenesis of two IFN-mediated autoinflammatory diseases, CANDLE and SAVI, with Aicardi Goutieres syndrome (AGS) and monogenic forms of SLE (monoSLE) caused by loss-of function mutations in complement 1 (C1q) or the DNA nucleases, DNASE1 and DNASE1L3. We outline differences in intracellular signaling pathways that fuel a pathologic type I IFN amplification cycle. While IFN amplification is caused by predominantly innate immune cell dysfunction in SAVI, CANDLE, and AGS, autoantibodies to modified RNA and DNA antigens interact with tissues and immune cells including neutrophils and contribute to IFN upregulation in some SLE patients including monoSLE, thus justifying a grouping of "autoinflammatory" and "autoimmune" interferonopathies. Understanding of the differences in the cellular sources and signaling pathways will guide new drug development and the use of emerging targeted therapies. PMID- 27678532 TI - Educational inequalities in premature mortality in Poland, 2002-2011: a population-based cross-sectional study. AB - BACKGROUND: The aim of the study is to evaluate the differences in premature mortality between educational groups of Polish inhabitants in 2002 and 2011. METHODS: The analysis included all deaths among inhabitants of Poland, aged 25-64 years, which occurred in 2002 (N=97 004) and 2011 (N=104 598). We calculated age standardised death rates (SDRs) and summary measures on inequalities. The relative index of inequality (RII) was calculated with Poisson regression. RESULTS: The SDR for Poland decreased from 285.7 per 100 000 in 2002 to 246.0 in 2011 among males with higher education and increased from 1141.0 in 2002 to 1183.0 in 2011 among males with lower secondary or less education (the rate ratio increased from 4.0 to 4.8). With regard to females with higher education, the SDR decreased from 127.2 per 100 000 in 2002 to 115.6 in 2011. Among females with lower secondary or less education, the SDR increased from 375.8 per 100 000 in 2002 to 423.1 in 2011 (the rate ratio increased from 3.0 to 3.7). The RII increased from 5.8 to 9.7 in the male group and from 4.4 to 8.3 in the female group. The greatest educational inequalities in 2011 were observed in females who died of cardiovascular diseases (RII=14.9) and lung cancer (RII=6.6) and in males who died of suicides (RII=19.3) and lung cancer (RII=11.9). CONCLUSIONS: Educational inequalities in premature mortality in Poland are growing. There is a need to implement health education programmes targeted at groups of the most poorly educated Polish inhabitants, especially for diseases resulting from smoking and excessive alcohol consumption. PMID- 27678533 TI - Treatment And Prevention for female Sex workers in South Africa: protocol for the TAPS Demonstration Project. AB - INTRODUCTION: Updated guidelines from the WHO recommend antiretroviral treatment for adults with HIV at any CD4 count and daily oral pre-exposure prophylaxis (PrEP) for people at substantial risk of HIV infection. However, implementation challenges may hinder the ability of programmes to translate these recommendations into successful practice. This demonstration project is the first to integrate PrEP and immediate treatment (ITx) for female sex workers (FSWs) in South Africa to answer operational research questions. METHODS AND ANALYSIS: This is a prospective cohort study where the main outcome is retention at 12 months. The study population is recruited into two arms across two urban sites: (1) PrEP for HIV-negative FSWs (n=400) and (2) ITx for HIV-positive FSWs with CD4 greater than national guidelines (n=300). We investigate process and other health indicators, uptake and use of PrEP and ITx through qualitative research, and evaluate cost-effectiveness analysis combined with estimates of impact through epidemiological modelling. ETHICS AND DISSEMINATION: The Treatment And Prevention for female Sex workers in South Africa (TAPS) Project was designed as an implementation study before emtricitabine/tenofovir disoproxil fumarate was licenced as an indication for PrEP in South Africa. Therefore, clinical trial requirements for ethical and South African Medicines Control Council approvals were followed. Results will be disseminated to participants, local health officials and other stakeholders, as well as in peer-reviewed journals and at conferences. PMID- 27678534 TI - Guidelines of the International Federation of Red Cross and Red Crescent Societies: an overview and quality appraisal using AGREE II. AB - OBJECTIVES: To appraise the quality of guidelines developed by the International Federation of Red Cross and Red Crescent Societies (IFRC) between 2001 and 2015. STUDY DESIGN: Cross-sectional. METHODS: 2 authors independently assessed the quality of IFRC guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Average domain scores were calculated and overall quality scores and recommendation for use were determined. RESULTS: Out of 77 identified guidelines, 27 met the inclusion criteria and were assessed. The domains with the highest average scores across guidelines were 'scope and purpose', 'clarity of presentation' and 'applicability'. The lowest scoring domains were 'rigour of development' and 'editorial independence'. No guideline can be 'recommended for immediate use', 23 guidelines are 'recommended with modifications' and 4 guidelines are 'not recommended'. CONCLUSIONS: The IFRC produces guidelines that should be adhered to by millions of staff and volunteers in 190 countries. These guidelines should therefore be of high quality. Up until now, the IFRC had no uniform guideline development process. The results of the AGREE II appraisal indicate that the quality of the guidelines needs to be improved. PMID- 27678535 TI - Correction: Descriptive, cross-country analysis of the nurse practitioner workforce in six countries: size, growth, physician substitution potential. PMID- 27678537 TI - Actual and preferred contraceptive sources among young people: findings from the British National Survey of Sexual Attitudes and Lifestyles. AB - OBJECTIVE: To describe actual and preferred contraceptive sources among young people in Britain and whether discordance between these is associated with markers of sexual risk behaviour or poor sexual health. DESIGN: Cross-sectional probability sample survey. SETTING: British general population. PARTICIPANTS: 3869 men and women aged 16-24 years interviewed for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) between 2010 and 2012. MAIN OUTCOME MEASURES: Reported source of contraceptive method(s) and preferred source if all were available and easily accessible. RESULTS: Of the 75% of young people (aged 16-24) who were heterosexually active (1619 women, 1233 men), >86% reported obtaining contraceptives in the past year. Most common sources were general practice (women, 63%) and retail (men, 60%): using multiple sources was common (women 40%, men 45%). Healthcare sources were preferred by 81% of women and 57% of men. Overall, 32% of women and 39% of men had not used their preferred source. This discordance was most common among men who preferred general practice (69%) and women who preferred retail (52%). Likelihood of discordance was higher among women who usually used a less effective contraceptive method or had an abortion. It was less likely among men who usually used a less effective method of contraception and men who were not in a steady relationship. CONCLUSIONS: Most young people in Britain obtained contraception in the past year but one-third had not used their preferred source. Healthcare sources were preferred. Discordance was associated with using less effective contraception and abortion among young women. Meeting young people's preference for obtaining contraception from healthcare sources could improve uptake of effective contraception to reduce unwanted pregnancies. PMID- 27678538 TI - Correction: Characteristics, treatment and in-hospital outcomes of patients with STEMI in a metropolitan area of a developing country: an initial report of the extended Jakarta Acute Coronary Syndrome registry. PMID- 27678536 TI - Risk assessment and suicide by patients with schizophrenia in secondary mental healthcare: a case-control study. AB - OBJECTIVES: To investigate the role of risk assessment in predicting suicide in patients with schizophrenia spectrum disorders (SSDs) receiving secondary mental healthcare. We postulated that risk assessment plays a limited role in predicting suicide in these patients. DESIGN: Retrospective case-control study. SETTING: Anonymised electronic mental health record data from the South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) (London, UK) linked with national mortality data. PARTICIPANTS: In 242 227 SLaM service users up to 31 December 2013, 635 suicides were identified. 96 (15.1%) had a SSD diagnosis. Those who died before 1 January 2007 (n=25) were removed from the analyses. Thus, 71 participants with SSD who died from suicide over the study period (cases) were compared with 355 controls. MAIN OUTCOME MEASURE: Risk of suicide in relation to risk assessment ratings. RESULTS: Cases were younger at first contact with services (mean+/-SD 34.5+/-12.6 vs 39.2+/-15.2) and with a higher preponderance of males (OR=2.07, 95% CI 1.18 to 3.65, p=0.01) than controls. Also, suicide occurred within 10 days after last contact with services in half of cases, with the most common suicide methods being hanging (14) and jumping (13). Cases were more likely to have the following 'risk assessment' items previously recorded: suicidal history (OR=4.42, 95% CI 2.01 to 9.65, p<0.001), use of violent method (OR=3.37, 95% CI 1.47 to 7.74, p=0.01), suicidal ideation (OR=3.57, 95% CI 1.40 to 9.07, p=0.01) and recent hospital discharge (OR=2.71, 95% CI 1.17 to 6.28, p=0.04). Multiple regression models predicted only 21.5% of the suicide outcome variance. CONCLUSIONS: Predicting suicide in schizophrenia is highly challenging due to the high prevalence of risk factors within this diagnostic group irrespective of outcome, including suicide. Nevertheless, older age at first contact with mental health services and lack of suicidal history and suicidal ideation are useful protective markers indicative of those less likely to end their own lives. PMID- 27678539 TI - Using multimedia tools and high-fidelity simulations to improve medical students' resuscitation performance: an observational study. AB - OBJECTIVES: The goal of our study was to shed light on educational methods to strengthen medical students' cardiopulmonary resuscitation (CPR) leadership and team skills in order to optimise CPR understanding and success using didactic videos and high-fidelity simulations. DESIGN: An observational study. SETTING: A tertiary medical centre in Northern Taiwan. PARTICIPANTS: A total of 104 5-7th year medical students, including 72 men and 32 women. INTERVENTIONS: We provided the medical students with a 2-hour training session on advanced CPR. During each class, we divided the students into 1-2 groups; each group consisted of 4-6 team members. Medical student teams were trained by using either method A or B. Method A started with an instructional CPR video followed by a first CPR simulation. Method B started with a first CPR simulation followed by an instructional CPR video. All students then participated in a second CPR simulation. OUTCOME MEASURES: Student teams were assessed with checklist rating scores in leadership, teamwork and team member skills, global rating scores by an attending physician and video-recording evaluation by 2 independent individuals. RESULTS: The 104 medical students were divided into 22 teams. We trained 11 teams using method A and 11 using method B. Total second CPR simulation scores were significantly higher than first CPR simulation scores in leadership (p<0.001), teamwork (p<0.001) and team member skills (p<0.001). For methods A and B students' first CPR simulation scores were similar, but method A students' second CPR simulation scores were significantly higher than those of method B in leadership skills (p=0.034), specifically in the support subcategory (p=0.049). CONCLUSIONS: Although both teaching strategies improved leadership, teamwork and team member performance, video exposure followed by CPR simulation further increased students' leadership skills compared with CPR simulation followed by video exposure. PMID- 27678540 TI - Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials.gov: a systematic review of registration details. AB - OBJECTIVES: To systematically assess registration details of ongoing randomised controlled trials (RCTs) targeting 10 common chronic conditions and registered at ClinicalTrials.gov and to determine the prevalence of (1) trial records excluding patients with concomitant chronic condition(s) and (2) those specifically targeting patients with concomitant chronic conditions. DESIGN: Systematic review of trial registration records. DATA SOURCES: ClinicalTrials.gov register. STUDY SELECTION: All ongoing RCTs registered from 1 January 2014 to 31 January 2015 that assessed an intervention targeting adults with coronary heart disease (CHD), hypertension, heart failure, stroke/transient ischaemic attack, atrial fibrillation, type 2 diabetes, chronic obstructive pulmonary disease, painful condition, depression and dementia with a target sample size >=100. DATA EXTRACTION: From the trial registration records, 2 researchers independently recorded the trial characteristics and the number of exclusion criteria and determined whether patients with concomitant chronic conditions were excluded or specifically targeted. RESULTS: Among 319 ongoing RCTs, despite the high prevalence of the concomitant chronic conditions, patients with these conditions were excluded in 251 trials (79%). For example, although 91% of patients with CHD had a concomitant chronic condition, 69% of trials targeting such patients excluded patients with concomitant chronic condition(s). When considering the co occurrence of 2 chronic conditions, 31% of patients with chronic pain also had depression, but 58% of the trials targeting patients with chronic pain excluded patients with depression. Only 37 trials (12%) assessed interventions specifically targeting patients with concomitant chronic conditions; 31 (84%) excluded patients with concomitant chronic condition(s). CONCLUSIONS: Despite widespread multimorbidity, more than three-quarters of ongoing trials assessing interventions for patients with chronic conditions excluded patients with concomitant chronic conditions. PMID- 27678541 TI - Study protocol for a multicentre randomised controlled trial: Safety, Tolerability, efficacy and quality of life Of a human recombinant alkaline Phosphatase in patients with sepsis-associated Acute Kidney Injury (STOP-AKI). AB - INTRODUCTION: Acute kidney injury (AKI) occurs in 55-60% of critically ill patients, and sepsis is the most common underlying cause. No pharmacological treatment options are licensed to treat sepsis-associated AKI (SA-AKI); only supportive renal replacement therapy (RRT) is available. One of the limited number of candidate compounds in clinical development to treat SA-AKI is alkaline phosphatase (AP). The renal protective effect of purified bovine intestinal AP has been demonstrated in critically ill sepsis patients. To build on these observations, a human recombinant AP (recAP) was developed, of which safety and efficacy in patients with SA-AKI will be investigated in this trial. METHODS: This is a randomised, double-blind, placebo-controlled, 4-arm, proof-of-concept, dose-finding adaptive phase IIa/IIb study, conducted in critically ill patients with SA-AKI. A minimum of 290 patients will be enrolled at ~50 sites in the European Union and North America. The study involves 2 parts. Patients enrolled during Part 1 will be randomly assigned to receive either placebo (n=30) or 1 of 3 different doses of recAP (n=30 per group) once daily for 3 days (0.4, 0.8 or 1.6 mg/kg). In Part 2, patients will be randomly assigned to receive the most efficacious dose of recAP (n=85), selected during an interim analysis, or placebo (n=85). Treatment must be administered within 24 hours after SA-AKI is first diagnosed and within 96 hours from first diagnosis of sepsis. The primary end point is the area under the time-corrected endogenous creatinine clearance curve from days 1 to 7. The key secondary end point is RRT incidence during days 1-28. ETHICS AND DISSEMINATION: This study is approved by the relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will reveal the efficacy of recAP for the improvement of renal function in critically ill patients with SA-AKI and will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT02182440; Pre-results. PMID- 27678543 TI - Patient characteristics, treatment and survival in pulmonary carcinoid tumours: an analysis from the UK National Lung Cancer Audit. AB - OBJECTIVES: Pulmonary carcinoid (PC) is a rare tumour with good prognosis following surgical resection. However, little is known regarding patient characteristics and use of other treatments modalities. Our objective was to review patient characteristics, treatment and survival for patients with PC and contrast these results with other forms of non-small cell lung cancer (NSCLC). SETTING: Audit data from UK National Lung Cancer Audit (NLCA) 2008-2013. PARTICIPANTS: 184 906 lung cancer cases were submitted to the NLCA. OUTCOME MEASURES: Primary outcome-survival rates between PC and NSCLC. Secondary outcome differences in performance status, lung function and treatment modality between PC and NSCLC. RESULTS: PC histology was recorded in 1341 (0.73%) patients and non carcinoid NSCLC histology in 162 959 (87.4%) cases. 91% of patients with PC had good performance status (Eastern Cooperative Oncology Group (ECOG) 0-1), compared with only 53% of NSCLC. 66% of PC had localised disease. Of all PC cases, 77% were treated with surgery, 6.2% received chemotherapy and 3.6% received radiotherapy, with the remainder treated with best supportive care. Overall 1 year and 3-year survival rates for PC were 92% and 84.7%, respectively. In contrast, 1-year and 3-year survival rates for NSCLC were 36.2% and 15.6%, However, 3-year survival for PC markedly decreased with worsening performance status and advanced disease to 23.8% for performance status ECOG 3-4 and 33.6% for stage IV disease. CONCLUSIONS: In contrast to other forms of NSCLC, the majority of patients with PC present with good performance status, preserved lung function and early stage disease amenable to surgical resection. However, 1 in 5 patients with PC has metastatic disease which is associated with poor prognosis, as is poor performance status at presentation. We believe these data will help clinicians provide accurate prognostic predictions stratified according to patient characteristics at presentation, as well as guide future clinical trials. PMID- 27678542 TI - Motor control exercise for symptomatic lumbar disc herniation: protocol for a systematic review and meta-analysis. AB - INTRODUCTION: Lumbar disc herniation (LDH) is a common condition in adults and can impose a heavy burden on both the individual and society. It is defined as displacement of disc components beyond the intervertebral disc space. Various conservative treatments have been recommended for the treatment of LDH and physical therapy plays a major role in the management of patients. Therapeutic exercise is effective for relieving pain and improving function in individuals with symptomatic LDH. The aim of this systematic review is to evaluate the effectiveness of motor control exercise (MCE) for symptomatic LDH. METHODS AND ANALYSIS: We will include all clinical trial studies with a concurrent control group which evaluated the effect of MCEs in patients with symptomatic LDH. We will search PubMed, SCOPUS, PEDro, SPORTDiscus, CINAHL, CENTRAL and EMBASE with no restriction of language. Primary outcomes of this systematic review are pain intensity and functional disability and secondary outcomes are functional tests, muscle thickness, quality of life, return to work, muscle endurance and adverse events. Study selection and data extraction will be performed by two independent reviewers. The assessment of risk of bias will be implemented using the PEDro scale. Publication bias will be assessed by funnel plots, Begg's and Egger's tests. Heterogeneity will be evaluated using the I2 statistic and the chi2 test. In addition, subgroup analyses will be conducted for population and the secondary outcomes. All meta-analyses will be performed using Stata V.12 software. ETHICS AND DISSEMINATION: No ethical concerns are predicted. The systematic review findings will be published in a peer-reviewed journal and will also be presented at national/international academic and clinical conferences. TRIAL REGISTRATION NUMBER: CRD42016038166. PMID- 27678544 TI - Dietary diversity, socioeconomic status and maternal body mass index (BMI): quantile regression analysis of nationally representative data from Ghana, Namibia and Sao Tome and Principe. AB - OBJECTIVES: To (a) assess the association between dietary diversity (DD) score, socioeconomic status (SES) and maternal body mass index (BMI), and (b) the variation of the effects of DD and SES at different points of the conditional distribution of the BMI. METHODS: The study used Demographic and Health Surveys round 5 data sets from Ghana, Namibia and Sao Tome and Principe. The outcome variable for the analysis was maternal BMI. The DD score was computed using 24 hour dietary recall data. Quantile regression (QR) was used to examine the relationship between DD and SES, and maternal BMI, adjusting for other covariates. The QR allows the covariate effects to vary across the entire distribution of maternal BMI. RESULTS: Women who consumed an additional unit of DD achieved an increase of 0.245 in BMI for those in the 90th quantile in Ghana. The effect of household wealth increases for individuals across all quantiles of the BMI distribution and in all the 3 countries. A unit change in the household wealth score was associated with an increase of 0.038, 0.052 and 0.065 units increase in BMI for individuals in the 5th quantile in Ghana, Namibia and Sao Tome and Principe, respectively. Also, 0.237, 0.301 and 0.174 units increased for those in the 90th quantile in Ghana, Namibia and Sao Tome and Principe, respectively. Education had a significant positive effect on maternal BMI across all quantiles in Namibia and negative effect at the 5th, 10th and 90th quantiles in Sao Tome and Principe. CONCLUSIONS: There is heterogeneity in the effects of DD and SES on maternal BMI. Studies focusing on the effects of diet and socioeconomic determinants on maternal BMI should examine patterns of effects at different points of the conditional distribution of the BMI and not just the average effect. PMID- 27678545 TI - Randomised controlled trial of effect of whole soy replacement diet on features of metabolic syndrome in postmenopausal women: study protocol. AB - INTRODUCTION: Metabolic syndrome (MetS) is a public health problem in postmenopausal women. Whole soy foods are rich in unsaturated fats, high quality plant protein and various bioactive phytochemicals that may have a beneficial role in the management of MetS. The aim of the study is to examine the effect of whole soy replacement diet on the features of MetS among postmenopausal women. METHODS AND ANALYSIS: This will be a 12-month, randomised, single-blind, parallel controlled trial among 208 postmenopausal women at risk of MetS or with early MetS. After 4 weeks' run-in, subjects will be randomly allocated to one of two intervention groups, whole soy replacement group or control group, each for 12 months. Subjects in the whole soy group will be required to include four servings of whole soy foods (containing 25 g soy protein) into their daily diet iso calorically, replacing red or processed meat and high fat dairy products. Subjects in the control group will remain on a usual diet. The outcome measures will include metabolic parameters as well as a 10-year risk for ischaemic cardiovascular disease. We hypothesise that the whole soy substitution diet will notably improve features of MetS in postmenopausal women at risk of MetS or with early MetS. The study will have both theoretical and practical significance. If proven effective, the application of the whole soy replacement diet model will be a safe, practical and economical strategy for MetS prevention and treatment. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee of the Chinese University of Hong Kong. The results will be disseminated via conference presentations and papers in academic peer reviewed journals. Data files will be deposited in an accessible repository. TRIAL REGISTRATION NUMBER: NCT02610322. PMID- 27678546 TI - Strategies and impacts of patient and family engagement in collaborative mental healthcare: protocol for a systematic and realist review. AB - INTRODUCTION: Collaborative mental healthcare (CMHC) has garnered worldwide interest as an effective, team-based approach to managing common mental disorders in primary care. However, questions remain about how CMHC works and why it works in some circumstances but not others. In this study, we will review the evidence on one understudied but potentially critical component of CMHC, namely the engagement of patients and families in care. Our aims are to describe the strategies used to engage people with depression or anxiety disorders and their families in CMHC and understand how these strategies work, for whom and in what circumstances. METHODS AND ANALYSIS: We are conducting a review with systematic and realist review components. Review part 1 seeks to identify and describe the patient and family engagement strategies featured in CMHC interventions based on systematic searches and descriptive analysis of these interventions. We will use a 2012 Cochrane review of CMHC as a starting point and perform new searches in multiple databases and trial registers to retrieve more recent CMHC intervention studies. In review part 2, we will build and refine programme theories for each of these engagement strategies. Initial theory building will proceed iteratively through content expert consultations, electronic searches for theoretical literature and review team brainstorming sessions. Cluster searches will then retrieve additional data on contexts, mechanisms and outcomes associated with engagement strategies, and pairs of review authors will analyse and synthesise the evidence and adjust initial programme theories. ETHICS AND DISSEMINATION: Our review follows a participatory approach with multiple knowledge users and persons with lived experience of mental illness. These partners will help us develop and tailor project outputs, including publications, policy briefs, training materials and guidance on how to make CMHC more patient-centred and family-centred. PROSPERO REGISTRATION NUMBER: CRD42015025522. PMID- 27678547 TI - Female genital cosmetic surgery: a cross-sectional survey exploring knowledge, attitude and practice of general practitioners. AB - OBJECTIVE: To explore general practitioner's (GP) knowledge, attitudes and practice regarding female genital cosmetic surgery (FGCS) in Australia. DESIGN: Cross-sectional survey. SETTING: Australia. SAMPLE: GPs who attended a women's health seminar and GPs who subscribed to a non-governmental, national health professional organisation database that provides education to primary care professionals. METHOD: A national online survey of GPs was conducted for the 10 week period, starting 1 week prior and 2 months after a Women's Health seminar was held in Perth on 8 August 2015. 31 questions prompted GPs' knowledge, attitudes and practice in managing patients asking about FGCS. RESULTS: The survey was fully completed by 443 GPs; 54% had seen patients requesting FGCS. Overall, 75% (95% CI 71% to 79%) of GPs rated their knowledge of FGCS as inadequate and 97% (95% CI 94% to 99%) had been asked by women of all ages about genital normality. Of those who had seen patients requesting FGCS, nearly half (44%, 95% CI 38% to 51%) reported they had insufficient knowledge of risks of FGCS procedures and 35% (95% CI 29% to 41%) reported seeing females younger than 18 years of age requesting FGCS. Just over half (56%, 95% CI 51% to 60%) of the GPs felt that women should be counselled before making a referral for FGCS. More than half the GPs suspected psychological disturbances in their patients requesting FGCS such as depression, anxiety, relationship difficulties and body dysmorphic disorder. CONCLUSIONS: GPs see women of all ages presenting with genital anatomy concerns and in those who request FGCS, GPs often suspected a range of mental health difficulties. GPs require greater education to support their patients who request FGCS. PMID- 27678548 TI - Physical activity among medical students in Southern Thailand: a mixed methods study. AB - OBJECTIVES: The study aimed to investigate the prevalence of physical activity (PA) and factors influencing PA behaviours among medical students in Southern Thailand. DESIGN: The study implemented a mixed methods approach. The sequential design consisted of 2 phases: a survey followed by in-depth interviews. SETTING: The study was conducted in the 3 campuses of a medical school in Southern Thailand. The preclinical students (years 1-3) studied general and basic science subjects at Nakhon Si Thammarat campus. The clinical students (years 4-6) received clinical training and hospital attachments at Trang or Phuket campuses. Total number of students was 285, with 46-48 students in each class. The study was conducted from September 2015 to February 2016. PARTICIPANTS: Participants were medical students, 18 years old and above, from 3 campuses without disabilities or medical conditions which limited their ability to perform PA. OUTCOME MEASURES: The prevalence of the recommended levels of PA was measured using Global Physical Activity Questionnaire (GPAQ). The association between the demographic data and the recommended PA levels were analysed by univariate and multivariate analysis. In-depth interviews and thematic analysis were completed to explore PA behaviours. RESULTS: A total of 279 (response rate 97.9%) medical students participated in the study. Approximately half (49.5%) of the participants were physically active. The median total energy use was 540 metabolic equivalent-min/week (range 0-5640). Male and preclinical students were more likely to be physically active (p<0.05). Twenty-four in-depth interviews were conducted. Supportive factors included social support from friends and families. Study-related activities and overtime shift work were barriers. CONCLUSIONS: More than half of the medical students have insufficient PA because of study-related activities and overtime shift work. Future studies should focus on finding ways to improve PA in clinical and female students in Thailand. PMID- 27678549 TI - Neurobehavioral effects of vigabatrin and its ability to induce DNA damage in brain cells after acute treatment in rats. AB - RATIONALE: Vigabatrin (VGB) is a drug indicated mostly for the treatment of spasms in childhood and West's syndrome patients. This drug inhibits irreversibly the enzyme GABA-transaminase (GABA-T), increasing GABA concentrations and enhancing GABAergic neurotransmission in the brain, which is known to induce behavioral changes. OBJECTIVES: The aims of this study were to evaluate the effects of VGB in the short-term memory (STM), long-term memory (LTM), motivation, locomotion, and exploratory behavior tests and to detect deleterious or protective effects on DNA in target tissues of the drug. METHODS: Male Wistar rats were treated with a single dose of VGB (100, 250, or 500 mg/kg) or saline solution before the inhibitory avoidance and open-field tasks. DNA damage was evaluated using the alkaline comet assay in peripheral blood, cerebral cortex, and hippocampus after behavioral testing. RESULTS: There was no significant difference in the inhibitory avoidance task between the treated groups and the saline group. In all tested doses, VGB reduced the number of rearings in the open field task. Besides, VGB 500 mg/kg affected locomotion, though it was not able to induce any DNA damage. CONCLUSIONS: VGB did not affect STM and LTM, but the drug impaired the exploration and locomotion likely associated with its sedative effect. In addition, no DNA damage in cortex and hippocampus was detected after behavioral testing, when brain GABA levels are already increased. PMID- 27678550 TI - A test of the cognitive-enhancing potential of low-dose mecamylamine in healthy non-smokers. AB - RATIONALE: The beneficial effects of nicotinic acetylcholine receptor (nAChR) agonists on cognitive performance have been widely shown. Paradoxically, recent preclinical studies employing extremely low doses of nAChR antagonists have also found cognitive enhancement, perhaps pointing to a novel treatment mechanism for cognitive deficits. OBJECTIVES: The aim was to test whether low doses of the nAChR antagonist mecamylamine would benefit performance in human volunteers. METHODS: The study employed a double-blind within-subject design. Over four separate days, healthy adult non-smokers (n = 23) were tested with placebo and three trace doses of mecamylamine (0.25-1 mg, p.o.), adjusted for body weight. Participants performed three computerized tasks: a task of spatial selective attention and stimulus detection, the rapid visual information processing task (RVIPT) taxing sustained attention and working memory, and a change detection short-term memory task. Subjective state and vital signs were assessed repeatedly. RESULTS: Mecamylamine did not improve performance in any of the tasks. Any trends that were observed instead pointed toward performance impairment. Mecamylamine also had no effects on subjective state or vital signs. CONCLUSIONS: The present results do not support the hypothesized cognitive enhancing potential of low doses of mecamylamine. Contrary to preclinical reports, these findings speak against low-dose nAChR antagonism as a novel avenue for treating cognitive deficits. PMID- 27678552 TI - Urine ethanol concentration and alcohol hangover severity. AB - BACKGROUND: The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity. METHODS: N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms. RESULTS: Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems. CONCLUSION: Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms. PMID- 27678551 TI - Choice between delayed food and immediate oxycodone in rats. AB - RATIONALE: The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. OBJECTIVES: To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 MUg/kg) and delayed delivery of palatable food pellets. RESULTS: Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. CONCLUSIONS: These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction. PMID- 27678554 TI - Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders. AB - BACKGROUND: About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities. OBJECTIVES: 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children. SEARCH METHODS: In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism. DATA COLLECTION AND ANALYSIS: Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Two small studies involving 116 children, mainly boys between 10 and 18 years of age, met the inclusion criteria. One study was conducted in a school setting, the other at a specialised clinic. Both studies used three months of a combination of omega-3 and omega-6 supplements as the intervention compared with placebo. Although both studies had generally low risk of bias, we judged the risk of reporting bias as unclear in one study, and as high in the other study. In addition, one of the studies was funded by industry and reported active company involvement in the study.None of the studies reported data on the primary outcomes of reading, writing, spelling and mathematics scores, as assessed by standardised tests.Evidence of low quality indicates that supplementation of PUFAs did not increase the risk of gastrointestinal disturbances (risk ratio 1.43, 95% confidence interval 0.25 to 8.15; two studies, 116 children). Investigators reported no other adverse effects.Both studies reported attention deficit hyperactivity disorder (ADHD)-related behaviour outcomes. We were unable to combine the results in a meta-analysis because one study reported findings as a continuous outcome, and the other as a dichotomous outcome. No other secondary outcomes were reported.We excluded one study because it used a cointervention (carnosine), and five other studies because they did not provide a robust diagnosis of a specific learning disorder. We identified one ongoing study and found three studies awaiting classification. AUTHORS' CONCLUSIONS: Evidence is insufficient to permit any conclusions about the effect of PUFAs on the learning abilities of children with specific learning disorders. Well-designed RCTs with clearly defined populations of children with specific learning disorders who have been diagnosed by standardised diagnostic criteria are needed. PMID- 27678553 TI - Dementia and Traffic Accidents: A Danish Register-Based Cohort Study. AB - BACKGROUND: As a consequence of a rapid growth of an ageing population, more people with dementia are expected on the roads. Little is known about whether these people are at increased risk of road traffic-related accidents. OBJECTIVE: Our study aims to investigate the risk of road traffic-related accidents for people aged 65 years or older with a diagnosis of dementia in Denmark. METHODS: We will conduct a nationwide population-based cohort study consisting of Danish people aged 65 or older living in Denmark as of January 1, 2008. The cohort is followed for 7 years (2008-2014). Individual's personal data are available in Danish registers and can be linked using a unique personal identification number. A person is identified with dementia if the person meets at least one of the following criteria: (1) a diagnosis of the disease in the Danish National Patient Register or in the Danish Psychiatric Central Research Register, and/or (2) at least one dementia diagnosis-related drug prescription registration in the Danish National Prescription Registry. Police-, hospital-, and emergency room-reported road traffic-related accidents occurred within the study follow-up are defined as the study outcome. Cox proportional hazard regression models are used for the main analysis. RESULTS: Our study protocol has 3 phases including data collection, data analysis, and reporting. The first phase of register-based data collection of 853,228 individual's personal information was completed in August, 2016. The next phase is data analysis, which is expected to be finished before December 2016, and thereafter writing publications based on the findings. The study started in January 2016 and will end in December 2018. DISCUSSION: This study covers the entire elderly population of Denmark, and thereby will avoid selection bias due to nonparticipation and loss to follow-up. Furthermore, this ensures that the study results are reliable and generalizable. However, underreporting of traffic-related accidents may occur, which will limit estimation of absolute risks. PMID- 27678555 TI - Does the Difference in Fascial Closure Surgical Technique Affect Post-Operative Pain? PMID- 27678556 TI - Trends Over Time and Surgical Outcomes of Abdominal, Mini-Laparotomy, and Traditional and Robotic-Assisted Laparoscopy With and Without Tandem Mini Laparotomy: A Comparison of Myomectomy Techniques. PMID- 27678557 TI - GEARS - An Objective Tool to Differentiate Robotic Surgical Skill and Experience. PMID- 27678558 TI - The Use of a Closable Polyurethane Bag for Power Morcellation. PMID- 27678559 TI - LibrataTM - A Fully Hand-Held Endometrial Ablation Device: Proof Of Concept Using Extirpated Human Uteri. PMID- 27678560 TI - Review and Outcomes of Power Morcellation Using an Innovative Contained Bag System. PMID- 27678561 TI - Microablative Fractional CO2 Laser for Vulvovaginal Atrophy in Women With a History of Breast Cancer. PMID- 27678563 TI - Myosure Hysteroscopic Morcellation for the Management of Submucous Fibroids in an Out-Patient Hysteroscopy Setting. PMID- 27678562 TI - Automatic Contraction Detection During the Menstrual Cycle By Electrohysterography. PMID- 27678564 TI - The First Experience of Computer-Assisted Image Guidance in Laparoscopic Surgery: The Targeting Animation Guidance (TAG) System. PMID- 27678565 TI - Total Laparoscopic Hysterectomy: Single Surgeon Experience in a Regional Centre After Changing Uterine Manipulator and Surgical Technique. PMID- 27678566 TI - Initial Gynecologic Experience Using the VITOM(r) HD Exoscope for Vaginal Surgery. PMID- 27678567 TI - Vaginal Dilation in Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome. PMID- 27678568 TI - Single-Port Laparoscopic Neosalpingostomy for Hydrosalpinx. PMID- 27678569 TI - An Efficient Technique to Manually Morcellate Very Large Uteri Within an Enclosed Endoscopic Bag: Our Five-Year Experience. PMID- 27678570 TI - Randomized Comparison of Veress Needle Intraperitoneal Placement (VIP) at Caudaly Displaced Umbilicus Versus Left Upper Quadrant (LUQ) During Laparoscopic Entry. PMID- 27678571 TI - Direct Supply Cost Per Case (DSCPC) of Minimally Invasive Hysterectomy. PMID- 27678572 TI - The Ergonomics of Laparoscopic Surgery in Live Surgical Environments. PMID- 27678573 TI - Clinical Application of Morcellation: Provider Perceptions Survey (The CAMPPS Study). PMID- 27678575 TI - Tackling Uterine Artery at the Origin Is Safe and Effective for TLH. PMID- 27678574 TI - Standard Surgical Boundary, Surgical Results, and Outcomes of Systemic Laparoscopic Para-Aortic Lymphadenectomy Up to the Left Renal Vein Level for Women With Gynecologic Cancers. PMID- 27678576 TI - Vaginal Length and Sexual Function Following Total Laparoscopic Hysterectomy. PMID- 27678577 TI - Comparing Two Devices of Uterine Manipulation and Vaginal Fornix Delineation at Total Laparoscopic Hysterectomy - Preliminary Results. PMID- 27678578 TI - Extra-Corporeal In-Bag Manual Morcellation for Uterine Specimen Extraction: Analysis of 350 Consecutive Cases. PMID- 27678579 TI - Intra-Abdominal Space at Different Pressures and Level of Block, Consequences and Benefit of Low Pressure During Laparoscopy. PMID- 27678580 TI - Hysterectomy Trends Before and After the FDA Morcellator Warning: Have We Changed Our Practice and Perioperative Outcomes? PMID- 27678581 TI - 3-Month Versus 6-Month Treatment With Ulipristal Acetate Prior to Laparoscopic Hysterectomy of Large Myomatous Uteri. PMID- 27678582 TI - Incidence of Endometrial Hyperplasia or Carcinoma at the Time of Endometrial Ablation. PMID- 27678583 TI - Endometrial Pipelle Biopsy Identifying a Polyp Versus Office Hysteroscopy. PMID- 27678584 TI - Robotically-Assisted Radical Trachelectomy. PMID- 27678585 TI - Evaluation of Symptom Resolution in Patients With a Small Number of Myomas Following Robotic-Assisted Laparoscopic Myomectomy. PMID- 27678586 TI - Comparing the Robotic Single-Port Approach to Multi-Port, for Pelvic Lymph Node Dissection in the Treatment of Endometrial Pathology. PMID- 27678587 TI - Comparison of Levonorgestrel Intrauterine Device and Endometrial Ablation in the Treatment of Abnormal Uterine Bleeding. PMID- 27678588 TI - Endometrial Sampling After Ablation Therapy. PMID- 27678590 TI - Reproductive Outcome Analysis of 286 Women Who Underwent Hysteroscopic Septum Resection for Complete and Partial Septum of the Uterus. PMID- 27678589 TI - The Use of Pediatric Foley Catheter After Operative Hysteroscopy for Intrauterine Pathology in Over a Thousand Patients Was Not Associated With Ascending Infection. PMID- 27678591 TI - Should Office Hysteroscopy be Done Routinely Before First ICSI Trial? PMID- 27678592 TI - Comparison of Healthcare Costs Among Commercially-Insured Women in the U.S. Who Undergo Hysteroscopic Sterilization vs. Laparoscopic Bilateral Tubal Ligation Sterilization. PMID- 27678593 TI - Hysteroscopy Before In Vitro Fertilization (IVF): The Safety and Diagnostic Value. PMID- 27678594 TI - Hysteroscopy Diagnostic Consultation in Case of Postmenopausal Bleeding: Results, Feasibility and Performance. PMID- 27678595 TI - Contribution of a Virtual Hysteroscopic Simulator in the Learning of Hysteroscopic Myoma Resection. PMID- 27678596 TI - Evaluation of Vaginal Bleeding After Endometrial Ablation. PMID- 27678597 TI - Postpartum Sterilization: Could Bilateral Salpingectomy Replace Tubal Ligation? PMID- 27678598 TI - Initial Experience With a Novel Bipolar Hysteroscopic Tissue Removal System: A pilot Study Using the Symphion(r) System to Perform Office Polypectomy and Myomectomy. PMID- 27678599 TI - Robotic Laparoendoscopic Single Site Radical Hysterectomy With Sentinel Lymph Node Mapping and Pelvic Lymphadenectomy for Cervical Cancer. PMID- 27678600 TI - Laparoscopic Radical Trachelectomy in a Young Patient With Early Cervical Cancer. PMID- 27678601 TI - Robotic Lymph Node Dissection: Anatomy and Surgical Techniques. PMID- 27678602 TI - Making Clear of the Structure of Vesicouterine Ligament for Laparoscopic Radical Hysterectomy. PMID- 27678603 TI - Laparoscopic Debulking Pelvic Lymphadenectomy in Cervical Cancer. PMID- 27678604 TI - Laparoscopic Para-Aortic Lymphadenectomy (LPAL): Standard Surgical Boundary and Technique. PMID- 27678605 TI - Total Laparoscopic Nerve Sparing Radical Hysterectomy for Cervical Cancer and Retossigmoidectomy for Deep Intestinal Endometriosis in a Patient With Uterus Didelphys. PMID- 27678607 TI - Laparoscopic Excision of Isolated Para-Aortic Lymph Node Recurrence. PMID- 27678606 TI - Robotic Pelvic Lymphadenectomy in Pregnancy. PMID- 27678608 TI - A Rare Complication of Sacrocolpopexy. PMID- 27678609 TI - Cystoscopic Evaluation of Ureteral Jets: Alternatives to Indigo Carmine. PMID- 27678610 TI - Post-Hysterectomy Laparoscopic Uterosacral Ligament Suspension. PMID- 27678611 TI - Surgical Excision of Urethral Prolapse. PMID- 27678612 TI - Hybrid Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse With Severe Cystocele. PMID- 27678613 TI - Chronic 3rd Degree Laceration Repair. PMID- 27678615 TI - Robotic Resection of Pelvic Retroperitoneal Leiomyosarcoma. PMID- 27678614 TI - Sacrospinous Ligament Fixation: An Instructional Video Filmed Using a Vaginally Mounted High-Definition Camera. PMID- 27678616 TI - Sacrouteropexy: New Technique. PMID- 27678617 TI - Urinary Tract Identification and Protection in Gynecologic Surgery. PMID- 27678618 TI - Robotic-Assisted Uterine Artery Ligation: A Feasible Method for Huge or Unusual Myomectomy. PMID- 27678619 TI - Robotic Single-Site Endometriosis Resection Using Firefly Technology. PMID- 27678620 TI - Multifocal Intestinal Endometriosis and Retrocervical Mantle Shape Endometriosis. The Robotic Treatment - State-of-the-Art. PMID- 27678621 TI - Tips and Tricks: Single-Site Robotic Myomectomy. PMID- 27678622 TI - Robotic-Assisted Laparoscopic Treatment of Ureteral Endometriosis. PMID- 27678623 TI - Techniques for Efficiently Performing a Gastrocollic Omentectomy by a Robotic Approach. PMID- 27678624 TI - Robotic Resection of Intravesical Polypropylene Mesh Following Tension Free Tape Procedure. PMID- 27678625 TI - Robotic Excision of Diaphragm Metastases With Liver Involvement. PMID- 27678626 TI - A Model for Resection of Endometriosis: A Feasibility Study. PMID- 27678627 TI - Necessity of Morcellation at Time of Vaginal Hysterectomy. PMID- 27678628 TI - Repair of a Cystotomy During a Robot-Assisted Right Ureterolysis and Upper Vaginectomy: Review of Anatomy and Surgical Technique. PMID- 27678630 TI - The Six View Hysterectomy. PMID- 27678629 TI - Approach to the Obliterated Posterior Cul-De-Sac. PMID- 27678631 TI - Transvaginal Morcellation Simulation Model. PMID- 27678632 TI - The Role of TAP Block in Ob/Gyn. PMID- 27678633 TI - Duplication of Steps of Laparoscopic Radical Hysterectomy By Gynaecology Fellows. PMID- 27678634 TI - A Pilot Study for Revaluating Robotic Uterine Manipulation. PMID- 27678635 TI - The "Better" Technique for Accessory Trocar Insertion. PMID- 27678636 TI - Common Errors to Avoid in Laparoscopic Hysterectomies. PMID- 27678637 TI - Laparoscopic Approach to Cornual Ectopic Pregnancy (CEP): Review of a Simplified Approach. PMID- 27678638 TI - Laparoscopic Resection of Cesarean Section Scar Ectopic Pregnancy and Isthmocele Repair. PMID- 27678639 TI - A Novel Approach to Laparoscopic Management and Repair of a Post-Operative Uretero-Vaginal Fistula. PMID- 27678640 TI - Laparoendoscopic Single-Site Radical Parametrectomy for Treatment of Cervix Cancer Diagnosed After Simple Hysterectomy. PMID- 27678641 TI - Principles and Techniques of Expert Laparoscopic Surgical Dissection. PMID- 27678642 TI - Surgical Approach to Total Laparoscopic Hysterectomy of Bicornuate Uteri With Obliteration of the Pouch of Douglas by Rectovesical Fusion. PMID- 27678643 TI - Laparoscopic Radical Hysterectomy and Lymphadenectomy. PMID- 27678644 TI - Temporary Uterine Artery Ligation at the Origin Prior to Laparoscopic Myomectomy. PMID- 27678645 TI - Hysteroscopic Procedure for Type I Myoma With Intrauterine Adhesions. PMID- 27678647 TI - Tips for Successful Laparoscopic Lysis of Adhesions and Enterolysis. PMID- 27678646 TI - Hysteroscopic Intrauterine Adhesiolysis Using "Ploughing" Technique With Cold Scissors. PMID- 27678649 TI - Laparoscopic Retrieval of a Retroperitoneal Hysteroscopic Microinsert Using Fluoroscopy. PMID- 27678648 TI - Treatment of Asherman's Syndrome in an Outpatient Hysteroscopy Setting. PMID- 27678650 TI - Hysteroscopy in the Diagnosis & Management of Persistent Retained Products of Conception (RPOC). PMID- 27678651 TI - Hysteroscopic Myomectomy. PMID- 27678652 TI - Tips for Hysteroscopic Sterilization With In-Situ Intrauterine Device. PMID- 27678654 TI - Hysteroscopic Metroplasty. PMID- 27678653 TI - Vasopressin Myoma Infiltration During Hysteroscopic Myomectomy. PMID- 27678656 TI - Treatment of Adenomyosis by Hysteroscopy. PMID- 27678655 TI - Resection of Uterine Septum Using the MyoSure Tissue Removal System. PMID- 27678657 TI - Hysteroscopic Multiple Myomectomy. PMID- 27678658 TI - Retained Products of Conception: A Hysteroscopic Directed Resection. PMID- 27678659 TI - Laparoscopic Resection of Pregnancy in Non-Communicating Uterine Horn. PMID- 27678660 TI - Laparoscopic-Assisted Transversus Abdominis Plane Blocks. PMID- 27678661 TI - Laparoscopic Posterior Exenteration. PMID- 27678662 TI - A Novel Approach to Overcoming Cervical Stenosis and False Passages. PMID- 27678663 TI - Optimizing Intra-Operative Visualization During Gynecologic Surgery. PMID- 27678664 TI - Suprapubic Transvesical Laparoscopic Repair for Vesico-Vaginal Fistula. PMID- 27678665 TI - Colpotomy Relaxing Incisions: A New Technique for the Facilitation of Removal of Large Hysterectomy Specimens Without the Use of Electromechanical Morcellation. PMID- 27678666 TI - Laparoscopic Supra-Levator Total Pelvic Exenteration in Advanced Case of Ca Cervix. PMID- 27678667 TI - Laparoscopic Neovagina and Neocervix Followed By Reconstruction With PTFE Graft/Buccal Mucosa and Pudendal Artery Perforator Flap. PMID- 27678668 TI - Ureteral Injury: Techniques for Ureteral Re-Anastamosis. PMID- 27678669 TI - The Bermuda Triangle An Easy Technique to Identify and Clip the Uterine Arteries. PMID- 27678670 TI - Step-By-Step: Three Stitch Technique for Laparoscopic Sterilization Reversal. PMID- 27678671 TI - Lateral Approach for Difficult Dissection of the Vesicovaginal Space During Hysterectomy. PMID- 27678672 TI - Laparoscopic Modification of the Osada Technique for Adenomyomectomy. PMID- 27678673 TI - Contained Morcellation Techniques During Laparoscopy. PMID- 27678674 TI - Skelton-Style Total Laparoscopic Hysterectomy. PMID- 27678675 TI - Laparoscopic Resection of 16 Week Pregnancy in a Rudimentary Uterine Horn. PMID- 27678676 TI - Laparoscopic Presacral Neurectomy: Anatomy and Surgical Technique. PMID- 27678677 TI - Split Thickness Skin Graft for Cervicovaginal Reconstruction in Congenital Atresia of Cervix. PMID- 27678678 TI - Extrinsic Ureteral Endometriosis: Tackling the Difficult Ureterolysis. PMID- 27678679 TI - An Extra Step to Prevent Troublesome Uterine Artery Bleeding: Retroperitoneal Dissection and Ligation of the Uterine Artery at the Source. PMID- 27678680 TI - Laparoscopic Surgical Management of Juvenile Cystic Adenomyosis. PMID- 27678681 TI - Combined Natural Orifice Single-Site Hysterectomy. PMID- 27678682 TI - Laparoscopic Excision of Interstitial Pregnancy. PMID- 27678683 TI - Single Incision Laparoscopic Hysterectomy for Severe Endometriosis. PMID- 27678684 TI - Discoid Resection of Invasive Rectosigmoid Endometriosis. PMID- 27678685 TI - Excision of Bladder Endometriosis Under Cystoscopic Guidance. PMID- 27678686 TI - Presentation and Management of Extra-Pelvic Endometriosis of the Abdominal Wall, Perineum and Umbilicus and Intra-Peritoneal Findings. PMID- 27678688 TI - Excision of Inguinal Endometriosis. PMID- 27678687 TI - Laparoscopic Diagnosis and Treatment of Superficial Endometriosis in a Teenage Patient. PMID- 27678689 TI - Two Cases of Urinary Tract Endometriosis - Two Reconstruction Method After Segmental Resection. PMID- 27678690 TI - Conservative Laparoscopy for the Obliterated Posterior Cul-De-Sac. PMID- 27678691 TI - Single-Site Assisted Laparoscopy, "SAL". PMID- 27678692 TI - Total Laparoscopic Hysterectomy for Enlarged Fibroid Uterus. PMID- 27678693 TI - Laparoscopically-Assisted Utero-Vestibular Anastomosis in Patients With Uterine Cervix Atresia and Vaginal Aplasia. PMID- 27678694 TI - Laparoscopic Fertility-Saving Staging Surgery for Woman With Huge Pelvic Mass. PMID- 27678695 TI - A Simple Innovative Technique for Managing Large Cystic Benign Adnexal Masses Using Single Port Laparoscopic Surgery. PMID- 27678696 TI - Partial Cystectomy for Bladder Endometriosis. PMID- 27678698 TI - Natural Orifice Sacral Colpopexy. PMID- 27678697 TI - National Trends of Surgical Management of Ectopic Pregnancy. United States 1998 2011. PMID- 27678699 TI - A Novel Approach to Sacral Fixation During LSH and Sacrocervicopexy for Uterovaginal Prolapse. PMID- 27678700 TI - The Value of the Preoperative 1-Hour Pad Test With Pessary Insertion to Predict the Need for a Mid-Urethral Sling Following Pelvic Prolapse Surgery: A Cohort Study. PMID- 27678701 TI - The Utility of Near-Infrared Florescence Imaging in Robotic-Assisted Sacrocolpopexy (RASC). PMID- 27678702 TI - Laparoscopic Excision of Posterior Vaginal Wall Mesh. PMID- 27678703 TI - Seven Techniques of Laparoscopic Surgeon's Knot. PMID- 27678704 TI - Leiomyomatosis Peritonealis Disseminata That Caused Hydroureter in Association With Deep Infiltrating Endometriosis. PMID- 27678705 TI - Laparoscopic Surgery for Recurrent Deep Infiltrating Endometriosis Involving Pelvic Sidewall. PMID- 27678706 TI - A Multi-Disciplinary Approach for the Surgical Management of Bladder Endometriosis. PMID- 27678707 TI - Laparoscopic Resection of Uterosacral Ligaments in Deeply Infiltrating Endometriosis, Technique for the Prevention of Complications. PMID- 27678708 TI - Multidisciplinary Approach for Resection of Diaphragmatic Endometriosis with Perihepatic Adhesions. PMID- 27678709 TI - Applying the Principles of Oncological Surgery to Treat Complicated Stage IV Endometriosis. PMID- 27678710 TI - Ten Commandments for a Safe Ovarian Entrometriosis Treatment. PMID- 27678711 TI - Single-Site Robotic Excision of Bladder Endometriosis Utilizing Fluorescence Imaging and CO2 Laser Technology. PMID- 27678712 TI - Surgical Techniques for the Treatment of Bowel Endometriosis. PMID- 27678713 TI - Laparoscopic Rectovaginal Fistula Repair. PMID- 27678714 TI - Standardization of Technical Procedures in Colposacropexia Laparoscopic Gynecological Endoscopy at Santa Casa De Misericordia De Sao Paulo. PMID- 27678715 TI - FDA Approved Tissue Extraction - Instrumentation and Techniques. PMID- 27678716 TI - Laparoscopic Repair of a Post-Operative Para-Umbilical Incisional Hernia. PMID- 27678717 TI - Resection of Diaphragmatic Endometriosis Presenting With Full Thickness Fenestrations. PMID- 27678718 TI - Laparoscopic Ovarian Transposition in a Case With Mullerian Anomaly: Providing a Chance for Successful Oocyte Retrieval and Subsequent Pregnancy. PMID- 27678719 TI - Laparoscopic Removal of Essure Microinserts. PMID- 27678720 TI - Laparoscopic Approach by Hemi-Hysterectomy in Patient With Herlyn-Werner Wunderlich Syndrome. PMID- 27678721 TI - Laparoscopic Myomectomy and Myoma Retrieval Without Power Morcellation. PMID- 27678722 TI - Left Upper Quadrant Entry Technique. PMID- 27678723 TI - Laparoscopic BSO With Posterior Colpotomy for Specimen Retrieval. PMID- 27678724 TI - Laparoscopic Resection of Intestinal Endometriosis: The Linear Nodulectomy. PMID- 27678725 TI - Laparoscopic Excision of an Ovarian Remnant Within a Frozen Pelvis. PMID- 27678726 TI - Laparoscopic Uterine Retrieval With Preservation of Uterine Vascular Pedicles: Promising Application for Human Uterine Transplants. PMID- 27678727 TI - Tips, Tricks, and Risks of Laparoscopic Myomectomy: Presented With a Case of a Broad Ligament Fibroid. PMID- 27678728 TI - Airseal Bag Morcellation. PMID- 27678729 TI - Laparoscopy in Hemodynamicaly Unstable Patients: Some Tips & Tricks. PMID- 27678730 TI - A Lateral to Anterior Approach to the Scarred Bladder Flap and Anterior Abdominal Wall Adhesions at the Time of Laparoscopic Hysterectomy. PMID- 27678731 TI - A Case for Adenomyomectomy. PMID- 27678732 TI - Radiofrequency Ablation of Symptomatic Uterine Fibroids: The AcessaTM Procedure. PMID- 27678733 TI - Laparoscopic Abdominal Cerclage. PMID- 27678734 TI - Cheap and Easy: Laparoscopic Appendectomy Through the Umbilicus. PMID- 27678735 TI - Innovative Technique for Enclosed Morcellation Using a Surgical Glove. PMID- 27678736 TI - Robotic Single-Site Myomectomy: A Step-by-Step Tutorial. PMID- 27678737 TI - Laparoscopic Management of Broad Ligament and Cervical Fibroids With Reconstruction of Ectocervical Canal. PMID- 27678738 TI - Cyst Removal With Dilute Vasopressin. PMID- 27678739 TI - Percutaneous Laparoscopy in Gynecology. PMID- 27678740 TI - Introducing Larger Equipment: A Novel Method in Laparoscopic Surgery With Smaller Port Sites. PMID- 27678741 TI - Contained Hand Morcellation in a Novel FDA-Approved Bag. PMID- 27678742 TI - O-Ring Self Retractor for Post Partum Tubal Ligation. PMID- 27678743 TI - Cystosure - A Novel Technique Making Female Cystoscopy Safer, Simpler, and Standardized. PMID- 27678744 TI - Tissue Extraction for Minimally Invasive Surgery. PMID- 27678745 TI - NOTES Facilitated Single-Port Staging Surgery for Endometrial Cancer. PMID- 27678746 TI - Abdominal Approaches to Tissue Containment and Extraction in MIGS. PMID- 27678747 TI - A Technique of Vaginoscopic Mesh Excision from the Vaginal Vault After Sacrocolpopexy. PMID- 27678749 TI - Vaginal Tissue Extraction With a Contained Bag System. PMID- 27678748 TI - Removal of Retained Adherent Placental Remnants Using Hysteroscopy Endo-Operative System (HEOS). PMID- 27678750 TI - Assessing Ureteral Location in FireFlyTM Fluorescence Imaging Mode During da Vinci Hysterectomy. PMID- 27678751 TI - Small Bowel Segmental Resection and Reanastomosis With Appendectomy for Invasive Endometriosis. PMID- 27678752 TI - Heterotopic Pregnancy: A Case Report. PMID- 27678753 TI - Primary Abdominal Ectopic Pregnancy. Case Report. PMID- 27678754 TI - CO2 Laser Shaving Technique for Resection of Rectosigmoid Endometriosis. PMID- 27678755 TI - Pararectal Space Dissection for Treatment of Endometriosis. PMID- 27678756 TI - Now You See It: Using a 30 degrees Laparoscope for MIGS. PMID- 27678757 TI - In Situ Simulation: A Patient Safety Frontier. PMID- 27678758 TI - Endometriosis: Tools for the Frozen Pelvis. PMID- 27678759 TI - Isolated Tubal Torsion in Patient With Chronic Salpingitis: A Challenging Diagnosis. PMID- 27678760 TI - Nerve Sparing Rectosigmoid Resection and Low Rectal Anastomosis for Deep Pelvic Endometriosis. PMID- 27678761 TI - Simple Excision Technique for Complex Endometriosis. PMID- 27678763 TI - Resection of Large Endometriotic Nodule From Bladder With Full Thickness Bladder Wall Resection. PMID- 27678762 TI - Laparoscopic Shaving Surgery of Endometriotic Nodule on Anterior Rectal Wall. PMID- 27678764 TI - Does the Mode of Surgery for Hydrosalpinges Affect Outcome in In-Vitro Fertilization (IVF) Cycles? A Randomized Trial Comparing Laparoscopic Salpingectomy and Proximal Tubal Occlusion (PTO). PMID- 27678765 TI - Genital Tuberculosis in Female Infertility: An Enigma. PMID- 27678766 TI - Reproductive Outcomes of 10 Years Asherman's Surgery. PMID- 27678768 TI - Single-Port Laparoscopy for Deep Infiltrating Endometriosis Surgery. PMID- 27678767 TI - Laparoscopic Deep Infiltrating Endometriosis Surgery With PKS OMNI. PMID- 27678769 TI - Retroperitoneal Dissection of Ovarian Endometrioma Using J-Plasma Technology. PMID- 27678770 TI - Rectosigmoid Segmental Resection and Reanastamosis for Invasive Endometriosis. PMID- 27678771 TI - Laparoscopic Resection of Ureter and Bladder Endometriosis. PMID- 27678772 TI - Laparoscopic Approach and Surgical Tactic for Deep Endometriosis. PMID- 27678773 TI - Double Discoid Resection in Deep Intestinal Endometriosis. PMID- 27678774 TI - Transcervical Hysteroscopic Resection of Complete Uterus Septum. PMID- 27678775 TI - Hysteroscopic Excision of Cesarean Scar Ectopic. PMID- 27678776 TI - Hysteroscopic Resection of Large Endometrial Polyp Secondary to Tamoxifen Therapy for Breast Cancer. PMID- 27678777 TI - Management of False Passage in the Cervical Canal During Operative Hysteroscopy. PMID- 27678778 TI - Intraoperative Evaluation of Squamous Intraepithelial Lesions by Microcolpohysteroscopy. PMID- 27678779 TI - Laparoscopic Management of Juvenile Cystic Adenomyoma. PMID- 27678780 TI - Ultrasound in the Diagnosis of Endometriosis. PMID- 27678781 TI - Hysteroscopic Removal of Malpositioned Mirena IUD Embedded in Cesarean Scar Niche. PMID- 27678782 TI - Hysteroscopic Resection of a Placental Site Trophoblastic Nodule With a Hysteroscopic Tissue Removal System. PMID- 27678783 TI - Removal of Retained Products of Conception Using a Hysteroscopic Morcellator: A Safer Alternative. PMID- 27678784 TI - Hysteroscopic Huge Polypectomy With Randall Forceps Under Visual Guidence of Office Hysterescopy; An Alternative Method for Operative Hysteroscopy or Mechanical Removal Techiques. PMID- 27678786 TI - Hysteroscopic Tubal Occlusion Tips and Tricks. PMID- 27678785 TI - Hysteroscopic Myomectomy: Successful Repeated Removal of a Large Type 1 Submucosal Leiomyoma. PMID- 27678787 TI - Asherman's in Disguise: A Very Unusual Presentation. PMID- 27678788 TI - Laparoscopic Single-Site Myomectomy of 11 cm Intramural Fibroid. PMID- 27678789 TI - Laparoscopic Radical Hysterectomy. PMID- 27678790 TI - In Bag Mechanical Morcellation. PMID- 27678791 TI - Total Laparoscopic Hysterectomy: Didelphic Uterus. PMID- 27678793 TI - Patient at 15 Weeks Gestation With a Large Adnexal Mass. PMID- 27678792 TI - Laparoscopic Oophorectomy and Radical Lymph Node Dissection for a Recurrent Adenocarcinoma In Situ of the Cervix. PMID- 27678794 TI - Diagnostic Hysteroscopy: Preparation for a Successful Procedure. PMID- 27678795 TI - Articulating Enseal to Simply Singe Incision Hysterectomy With Uterosacral Ligament Suspension. PMID- 27678796 TI - Endometrioma Surgery: Can a Different Story Be Told? PMID- 27678797 TI - Hydrodissection Technique in Bilateral Ovarian Cystectomy for Dermoid Cysts. PMID- 27678799 TI - Myomectomy After Uliprisal Acetate. PMID- 27678798 TI - A Modified Technique of Temporary Suspension of the Ovary to the Anterior Abdominal Wall. PMID- 27678800 TI - Laparoscopic Double Purse-String Suture Technique and Its Fertility Outcome in Interstitial Pregnancy: A Review of 15 Cases. PMID- 27678801 TI - Abdominal Wall Bowel Adhesions Resection Using CO2 Laser. PMID- 27678802 TI - Laparoscopic Techniques of Ovarian Cystectomy in the Second Trimester. PMID- 27678803 TI - Accessory Trocar Site Herniation. A Case Report. PMID- 27678804 TI - Videolaparoscopy Debulking Lymphadenectomy in a Fallopian Tube Cancer Patient. PMID- 27678805 TI - Unusual Presentation of an Ovarian Cyst: Successful Laparoscopic Excision. PMID- 27678806 TI - Laparoscopic Management of Severe Post Ablation Syndrome. PMID- 27678807 TI - Lower Uterine Segment Myomectomy. PMID- 27678808 TI - The Suprapubic Port: The Key Element in an Enlarged Fibroid Uterus. PMID- 27678809 TI - Laparoscopic Removal of Bladder From the Uterine Niche With Retrograde Dissection. PMID- 27678810 TI - A Technique to Divide the Adnexal Ligaments for Huge Fibroids During Total Laparoscopic Hysterectomy. PMID- 27678811 TI - Laparoscopic Transabdominal Cerclage. PMID- 27678812 TI - Abdominal Migration of a Tubal Occlusive Device: A Laparoscopic Retrieval Method? PMID- 27678813 TI - Two Techniques of Vaginal Cuff Closure in Single Incision LESS Surgery. PMID- 27678814 TI - Ureteric Injury in Total Laparoscopic Hysterectomy Repaired by Laparoscopic Neoureterocystostomy. PMID- 27678816 TI - 10 Practical Steps in Laparoscopic Sacrohysteropexy. PMID- 27678815 TI - Techniques for Removing Pelvic Masses. PMID- 27678817 TI - Profuse Vaginal Discharge May Equally Suggest Adenoma Malignum and Lobular Endocervical Glandular Hyperplasia (LEGH), But Same Cover, Different Story. PMID- 27678818 TI - Total Laparoscopic Hysterectomy for Uteri Over 1Kg. PMID- 27678819 TI - Laparoscopic Management of a Ruptured Interstitial Pregnancy Associated With Massive Haemoperitoneum and History of Ipsilateral Salpingectomy. PMID- 27678821 TI - Laparoscopic Hysterectomy (LH): An Easy Technique to Decrease Bleeding With Titanium Clips on the Uterine Arteries. PMID- 27678820 TI - Uterine Suspension: A New Laparoscopic Technique. PMID- 27678822 TI - Laparoscopic Approach for Myomas in Complex and Unusual Sites. PMID- 27678823 TI - Laparoscopic Repair of Uterine Scar Dehiscence After Cesarean Section. PMID- 27678824 TI - Ovarian Cyst Saline Distention to Enhance Dissection Planes Upon Cystectomy. PMID- 27678825 TI - Hand-Assist Laparoscopic Surgery (HALS) for Giant Ovarian Cysts. PMID- 27678826 TI - 3-Port Micro-Laparoscopic Hysterectomy in a Modified Vertical Plane. PMID- 27678827 TI - Laparoscopic Hemihysterectomy for Noncommunicating Uterine Horn. PMID- 27678828 TI - Laparoscopy Para-Aortic Lymphadenectomy for Cervical Cancer. PMID- 27678829 TI - Laparoscopic Hysterectomy Morcelation in Bag. PMID- 27678830 TI - Excision of Ectopic Adrenocortical Tissue During Laparoscopy for Pelvic Endometriosis. PMID- 27678831 TI - Laparoscopic Repair of Rupture of Inferior Vena Cava. PMID- 27678832 TI - Introduction of a Novel Laparoscopic Sacro-Hystero-Pexy for Uterine Prolapse. PMID- 27678833 TI - Pneumo-Bag Morcellation Technique. PMID- 27678834 TI - Laparoscopic Excision of Extensive Endometriosis Infiltrating Ureter, Bladder, Recto-Sgimoid, Pelvic Sidewall and Repair of Injury to the External Iliac and Aberrant Obturator Vein. PMID- 27678835 TI - Laparoscopic Diverticular Abscess With Drainage. PMID- 27678836 TI - Management of Iatrogenic Bleeder in Laparoscopy. PMID- 27678837 TI - Laparoscopic Management of Multiple Submucousal Fibroids. PMID- 27678838 TI - Laparoscopic Removal of Streak Gonads in Turner Syndrome. PMID- 27678839 TI - Assessment of Pelvic Floor Musculature in Women With and Without Pelvic Pain Using Four Dimensional (4D) Ultrasound. PMID- 27678841 TI - Laparoscopic Extraperitoneal Inframesenteric and Infrarenal Aortic Lymphadenectomy. PMID- 27678840 TI - Treatment of Difficult Ectopic Pregnancies With Needle Aspiration and Local Infusion. PMID- 27678842 TI - Successful Uterine Isthmo-Vagina Anastomosis With Barbed Suture in Robotic Radical Trachelectomy. PMID- 27678843 TI - In-Bag Morcellation in LESS Surgery Using a XXL LapBag(r). PMID- 27678844 TI - Minimally Invasive Non-Laparoscopic Ovarian Cystectomy: A Unique Way to Approach Large Ovarian Cysts. PMID- 27678845 TI - Approach to Minimizing Bleeding at Multiple Myometcomy. PMID- 27678846 TI - Use of D50 as Distension Medium in Diagnostic Cystoscopy. PMID- 27678847 TI - Caput Medusae. PMID- 27678848 TI - Congenital Absence of the Utero-Ovarian Ligament: A Clinical Dilemma. PMID- 27678849 TI - Abdominal Morcellation After Laparoscopic Removal of Large Pelvic Masses: A New Technique. PMID- 27678850 TI - Laparoscopic Isthmocervical Cerclage with Mersilene Tape After Radical Vaginal Trachelectomy. PMID- 27678851 TI - Robotically-Assisted Laparoscopic Resection of Endometriosis Using Firefly Technology. PMID- 27678852 TI - Laparoscopic Radical Cervicectomy With Pelvic Lymphadenectomy. PMID- 27678853 TI - Total Laparoscopic Hysterectomy Using a New Uterine Manipulator With Colpotransillumination. PMID- 27678854 TI - Fitting Procedure for a Novel Vaginal Bowel Control System. PMID- 27678855 TI - Contemporary Techniques, Tools and Modifications in This New Era for the Minimally Invasive Gynecologist. PMID- 27678856 TI - Robotic Excision of Migrated Inguinal Hernia Mesh into the Paravesical Space. PMID- 27678857 TI - Endoscopic Inguinal Lymphadenectomy in Vulvar Cancer. PMID- 27678858 TI - Pelvic Congestion Syndrome. PMID- 27678859 TI - Laparoscopic Residual Parametrial Resection and Mesh Excision. PMID- 27678860 TI - Robotic-Assisted Laparoscopic Nerve Sparing Radical Hysterectomy. PMID- 27678861 TI - Laparoscopic Restaging Surgery in Patients With Unexpected Uterine Cancer. PMID- 27678862 TI - Vestibulectomy With Vaginal Advancement for Treatment of Vestibulodynia. PMID- 27678863 TI - Fimbrioplasty and Neosalpingostomy: Treating Infertility Tubal Factor. PMID- 27678864 TI - Tips for Laparoscopic Single Incision Abdominal Cerclage Placement. PMID- 27678865 TI - Robotic Single-Incision Myomectomy. PMID- 27678866 TI - Overcoming the Obstacles of Visualization in Robotically-Assisted Abdominal Cerclage Using Indocyanine Green. PMID- 27678867 TI - Laparoscopic Management of a Rudimentary Horn Pregnancy. PMID- 27678868 TI - Laparoscopic Bilateral Ovarian Transposition With Preservation of Tubes in Women With Medulloblastoma. PMID- 27678869 TI - Herlyn Werner Wunderlich Syndrome: Varying Presentations. PMID- 27678871 TI - Robot-Assisted Laparoscopic Repair of a Cesarean Scar Defect With Hysteroscopic Guidance. PMID- 27678870 TI - Laparoscopic Ovarian Transposition. PMID- 27678872 TI - Advanced Robotics: Removal of a 25cm Pelvic Mass. PMID- 27678873 TI - Case Report: Place of Trans-Abdominal Cerclage Using the da Vinci Robotic System in Infertility Patients With Incompetent Cervix. PMID- 27678874 TI - Robotic Single-Incision Ovarian Vein Ligation for Pelvic Congestion Syndrome. PMID- 27678875 TI - 2-Incision Single-Site + 1 Robotic Sacrocolpopexy. PMID- 27678876 TI - Robotic-Assisted Removal of Transvaginal Mesh, a Minimally-Invasive Approach. PMID- 27678877 TI - Robotic Single-Site Surgery in Gynecology: Advantages and Pitfalls. PMID- 27678878 TI - Robotic/ Laparoscopic Needle Retrieval. PMID- 27678879 TI - Resection of Broad Ligament Myoma. PMID- 27678880 TI - Broad Ligament Fibroid. PMID- 27678881 TI - Robotic Sacrocolpopexy Utilizing a Xenogenic Barrier. PMID- 27678882 TI - The Use of Alternative Agents to Indigo Carmine During Cystoscopic Evaluation of Ureteral Patency. PMID- 27678883 TI - A Novel Vaginoscopy Technique for Repair of a Vaginal Mesh Erosion. PMID- 27678884 TI - Sacrospinous Ligament Vaginal Vault Suspension - Anterior Approach. PMID- 27678885 TI - Robot-Assisted Myomectomy. PMID- 27678886 TI - Laser Laparascopy and Excision of Bladder Endometriosis With Operative Cystoscopy. PMID- 27678887 TI - Video Game Impact on Basic Robotic Surgical Skills. PMID- 27678888 TI - A Needs Assessment of Laparoscopic Emergency Simulation Training in Residency Programs. PMID- 27678889 TI - Vault Prolapse Repair Without Use of Mesh. PMID- 27678890 TI - Genetic Risk Factors of Large Myomas. PMID- 27678891 TI - Development and Validation of a Structured Curriculum for Laparoscopic Supracervical Hysterectomy. PMID- 27678892 TI - Trends in Obstetrics-Gynecology Subspecialization. PMID- 27678893 TI - Compliance With Follow-Up Among Patients Treated With Methotrexate for Suspected Ectopic Pregnancy in an Urban Community Setting. PMID- 27678894 TI - Pattern of Congenital Uterine Anomalies Among Infertile Women in Southwest Nigeria. PMID- 27678895 TI - Accurate Identification of Anatomical Structures in a Normal Female Pelvis During Laparoscopic Surgery: A Survey Amongst Trainees and Consultants in Obstetrics and Gynaecology. PMID- 27678896 TI - Impact of a Minimally Invasive Gynecologic Surgeon on Patient Length of Stay Following Laparoscopic Hysterectomy. PMID- 27678897 TI - Diagnostics and Treatment for Uterine Leiomyosarcomas in Norway in the Period 2000 to 2012. PMID- 27678898 TI - Hypoxia-Induced Genotype Switch in Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase Through the Up-Regulation of Cytidine Deaminase Regulates Postoperative Adhesion Development. PMID- 27678899 TI - The Effectiveness and the Effect of the Obstetrics and Gynecology Medical School Clerkship on Future Career Choice By Gender. PMID- 27678900 TI - Removal of Tension-Free Vaginal Tape-Obturator Mesh Arm for Persistent Groin Pain Following Vaginal Mesh Removal. PMID- 27678901 TI - Ultrasonographic Investigation of the Mechanisms Involved in Menstrual Cramps. PMID- 27678902 TI - Change in Sexual Function at One Year Among Women Undergoing Hysterectomy for Pain-Related Verses Non-Pain Indications. PMID- 27678903 TI - A Little Known Feature of a Common Condition: Dermoid Cysts in Twins: A Case Report. PMID- 27678904 TI - Multidisciplinary Team Collaboration for Creation and Implementation of the Post Surgical Rolling Wrap-Up: A Patient Safety Innovation. PMID- 27678905 TI - Interaction of Follicle Stimulating Hormone (FSH) and Body Mass Index (BMI) in a Large Cohort. PMID- 27678906 TI - Risk Factors for Changes of Fibrinolysis During Benign Adnexal Laparoscopic Surgery. PMID- 27678907 TI - Does the Order of Surgical Method of Training Affect Learning and Skill? A Comparison of Laparoscopy and Robotics. PMID- 27678908 TI - Correlation of Genetic Polymorphisms With Development of Uterus Hyperplastic Processes in Women of Russia's Central Region. PMID- 27678909 TI - Minimally Invasive Fellowship Training and Effect on Operative Mortality. PMID- 27678910 TI - Surgical Site Infection Reduction Initiative Following Abdominal Hysterectomy. PMID- 27678911 TI - The Morphological Features of the Proliferative Activity in Ectopic Endometrial Structures. PMID- 27678912 TI - Concerns and Expectations of Women Prior to Hysterectomy. A Cross-Sectional, Observational Study in Tauranga, New Zealand. PMID- 27678913 TI - Unusual Branch of External Iliac Artery. PMID- 27678915 TI - Importance of Comprehensive Care Including Genetic Counseling for Ovary Carcinoma Patients by Gynecologic Oncologist. PMID- 27678914 TI - Assesment of the Intrafascial Total Laparoscopic Histerectomy in the Academic Environment. PMID- 27678916 TI - The Effect of Emla Ointment and Diclofenac Gel in Reducing the Pain of Venipuncture in Parturient Women in Meshginshar, Iran. PMID- 27678917 TI - Impact of Current Video Game Playing on Robotic Simulation Skills Among Medical Students. PMID- 27678919 TI - Endometriosis and Depression: A Psychoimmune Vicious Cycle. PMID- 27678918 TI - Visualization of the Ureter During Laparoscopy: Current Methods and New Technology. PMID- 27678920 TI - Ultrasonic Energy (Harmonic Ace) Versus Advanced Bipolar Energy (Ligasure) in a Laparoscopic Hyterectomies. PMID- 27678922 TI - Introduction of Fundamentals of Laparoscopic Surgery (FLS) Program in Obstetrics and Gynecology (Ob/Gyn) Residency Training. PMID- 27678921 TI - Investigation of Compositions and Effect of Herbal Essential Oils Local Silybum Marianum, Foeniculum Vulgare and Glycyrrhiza Glabra on Cell Line of Stomach Cancer by MTT Assays in Ardabil, Iran. PMID- 27678923 TI - Influence of Physical Exercise on Endometriosis Experimentally Induced in Rats. PMID- 27678924 TI - Perioperative Outcomes for Robotic-Assisted Excision of Severe Deep Infiltrating Endometriosis. PMID- 27678925 TI - Effect of Cabergoline in Experimental Endometriosis in Rats. PMID- 27678926 TI - The Performance of "The Endometriosis Scan" Preoperatively for the Detection of Deep Infiltrating Endometriosis. PMID- 27678927 TI - Association Between Endometriosis and Surgical Site Infection in Women Undergoing Hysterectomy. PMID- 27678928 TI - Size of Rectosigmoid Endometriotic Nodule and Dyschezia: What's the Novelty? PMID- 27678929 TI - Increased Expression Levels of Metalloprotease, Tissue Inhibitor of Metalloprotease, Metallothionein, and p63 in Ectopic Endometrium. PMID- 27678930 TI - Complications During Pregnancy in Patients With Deep Infiltrating Endometriosis (DIE). PMID- 27678931 TI - Two Cases of Endometriosis Presenting with Catamenial Pneumothorax and Umbilical Lesions. PMID- 27678932 TI - Can Surgical "Warm-Up" With Instructor Feedback Improve Operative Performance of Surgical Trainees? PMID- 27678933 TI - Development of an Evidence-Based Virtual Reality Training Curriculum for Laparoscopic Hysterectomy. PMID- 27678935 TI - Laparoscopic Implantation of Electrodes for Bilateral Neurmodulation of the Pudendal Nerves and S3 Nerve Roots for the Treatment of Pelvic Pain and Voiding Dysfunction. PMID- 27678934 TI - Laparoscopic Hysterectomy Complicated By Endometriosis and Bilateral Dermoid Cysts. PMID- 27678936 TI - Deep Infiltrating Endometriosis of the Bowels - Experience of a Multidisciplinary Team With 179 Patients Submitted to Intestinal Resections. PMID- 27678937 TI - Concentration of IL-1beta and IL-8 in Blood Plasma and in Peritoneal Fluid of Women With External Genital Endometriosis. PMID- 27678938 TI - The Comparison Between 2mg Dienogest and High-Dose Medroxyprogesterone Acetate on Oral Treatment of Endometriosis. PMID- 27678939 TI - Receptivity of Endometrioid Heterotopias With Nodular and Diffuse Forms of Adenomyosis. PMID- 27678941 TI - Endometriosis Presenting With Massive Ascites and an Elevated CA-125. PMID- 27678940 TI - Diagnostic Accuracy of Rectal Endoscopic Sonography in Recto-Vaginal Endometrisois. PMID- 27678942 TI - Long-Term Evaluation of Clinical Results and Quality of Life for Deeply Infiltrating Pelvic Endometriosis. PMID- 27678943 TI - Surgical Treatment Affects Perceived Stress Differently in Women With Endometriosis: Correlation With Severity of Pain. PMID- 27678944 TI - Outcomes of the Surgical Treatment of Endometriosis Affecting the Right Colon and Appendix: A Series of 34 Patients. PMID- 27678945 TI - Rapid Effects of Estrogen on Intracellular Ca2+ Regulation in Junctional Myometrium Through the Menstrual Cycle in Uteri With and Without Adenomyosis. PMID- 27678946 TI - The Use of Modified Virtual Colonoscopy to Structure a Staging and Treatment Model for Rectogenital, Multifocal and Disseminated Endometriosis. PMID- 27678947 TI - Ovarian Reserve Reduction Due to Unintended Excision of Healthy Ovarian Tissue During Endometrioma Surgery: What is the Risk? Analysis of 170 Cases. PMID- 27678948 TI - Diagnose and Management of Ureteral Endometriosis: A Report of 24 Cases. PMID- 27678949 TI - Clinicopathological Features of Endometriosis in Abdominal Wall - Clinical Analysis of 151 Cases. PMID- 27678950 TI - Impact of Dienogest on Endometriomas Transvaginal Ultrasound Features and Symptoms. PMID- 27678951 TI - A Modified Technique of Temporary Suspension of the Ovary to the Anterior Abdominal Wall. PMID- 27678952 TI - Real-Time Transvaginal Elastography of Recto-Sigmoid Endometriotic Nodules: Correlation With Symptoms and Histology. PMID- 27678953 TI - Combined Transurethral and Laparoscopic Partial Cystectomy and Robot-Assisted Bladder Repair for the Treatment of Bladder Mulerianosis. PMID- 27678954 TI - A Randomised, Single-Blind Clinical Trial to Investigate the Effectiveness of Bipolar Versus Monopolar Diathermy Treatment on Pain Symptoms for Women With Newly Diagnosed Superficial Endometriosis: The Set Study (Superficial Endometriosis Treatment). PMID- 27678955 TI - Endometriosis in Adolescents: Referrals, Diagnosis, Treatment, and Outcomes. PMID- 27678956 TI - Protective Ileostomy in Colorectal Resection for Endometriosis: Is It Truly Protective? PMID- 27678957 TI - Laparoscopic Surgical Treatment of Pelvic Endometriosis - The Experience of a Portuguese Hospital Centre. PMID- 27678958 TI - Persistent Clinical Equipoise for Treatments of Superficial Endometriosis. PMID- 27678959 TI - Laparoscopic Management of Deep Pelvic Endometriosis With Minimal Complications: Three-Year Experience. PMID- 27678961 TI - Ovarian Preservation in Premenopausal Patients With Endometriosis. PMID- 27678960 TI - Endometriosis and Infertility Setup During Hysterossalpingogram. PMID- 27678962 TI - Surgical Treatment of Deep Infiltrating Endometriosis of the Rectum - Presentation of the Techniques Used in Laparoscopic Surgery. PMID- 27678963 TI - Resectoscopic Endometrial Ablation for Abnormal Uterine Bleeding and Endometrial Changes Associated With Tamoxifen Therapy in Women With Carcinoma of the Breast. PMID- 27678964 TI - Effect of Endometrial Ablation on Premenstrual Symptoms. PMID- 27678965 TI - Efficacy of Long-Term Post-Operative Oral Contraceptive Use for the Prevention of Endometrioma Recurrence in Adolescents. PMID- 27678966 TI - Rectovaginal Endometriosis Resection Without Stoma: Selection Criteria. PMID- 27678967 TI - Retroperitoneal Ureteral and Uterine Artery Identification During Robotic Hysterectomy: Learning Curve and Determinants of Improvement During Fellowship Training. PMID- 27678968 TI - Robot-Assisted Laparoscopic Myomectomy: A Comparison of Techniques. PMID- 27678969 TI - Safe and Effective Surgery for Septate Uterus: 21 Cases Treated By Hysteroscopic Metroplasty With Hysterography and Custom-Made Intra-Uterine Silicone Plate. PMID- 27678970 TI - Perioperative Complications Associated With 5249 Primary and 458 Repeat Resectoscopic Endometrial Ablations: Experience of a Single Surgeon. PMID- 27678971 TI - LiNA Medical LibrataTM for Endometrial Ablation: A Peri-Hysterectomy Study. PMID- 27678972 TI - Hysteroscopic Proximal Occlusion of Hydrosalpinges by Essure(r) in 32 Laparoscopic Contraindicated Patients Before Assisted Reproductive Technology (ART). PMID- 27678973 TI - Hysteroscopic Myomectomy After Uterine Embolization in Large Sized Submucosal Myoma. PMID- 27678974 TI - Ulipristal Acetate Prior to High Complexity Hysteroscopic Myomectomy: Prospective Study. PMID- 27678975 TI - Office Hysteroscopy in Postmenopausal Women: Feasibility and Correlation With Transvaginal Ultrasound. PMID- 27678976 TI - Microwave Endometrial Ablation: Prospective Case Review and Patient Satisfaction Survey. PMID- 27678977 TI - Reproductive Outcomes After Fibrous Tissue Excision Prior to IVF in Women With Arcuate Uterus. PMID- 27678978 TI - Minitouch Outpatient Endometrial Ablation Procedure. PMID- 27678979 TI - Office Hysteroscopy for the Removal of a Retained Intrauterine Device. PMID- 27678980 TI - Review of Outcomes of Patients Treated for Intrauterine Adhesions With Office Hysteroscopy and Hormone Replacement Therapy. PMID- 27678981 TI - Combined Treatment of Women With Cervical Pregnancy in Operative Gynecology. PMID- 27678982 TI - Relationship Between Hysteroscopic and Hystological Findings in Postmenopausal Asymptomatic Women With Thickened Endometrium. PMID- 27678983 TI - Prediction of Unsuccessful Endometrial Ablation Leading to Hysterectomy. PMID- 27678984 TI - Reproductive Outcome of Patients With Asherman's Syndrome After Hysteroscopic Adhesiolysis. PMID- 27678985 TI - A Prospective Comparison of the Biopsy Results from Curettage and Hysteroscopy in Postmenopausal Uterine Bleeding. PMID- 27678986 TI - Effect of Pretreatment With Dienogest Before Hysteroscopic Surgery. PMID- 27678987 TI - Are We Overestimating the Efficacy of Hysteroscopic Sterilization? A Case Series from an Urban Abortion Clinic. PMID- 27678988 TI - Hysteroscopic Markers: Endometrial Tuberculosis Versus Chronic Endometritis. PMID- 27678990 TI - Surgical Treatment Outcomes in Patients With Recurrent Pregnancy Loss Attributed to Septate Uterus. PMID- 27678989 TI - Morphologic and Histologic Changes in Hysterectomies After NovaSure Ablation: A Retrospective Chart Review. PMID- 27678991 TI - Age at Diagnosis and Mass Size as Clinical Indications for Hysteroscopic Mass Excision. PMID- 27678992 TI - Hysteroscopic Removal of Placental Remnants: A Randomized Trial Comparing Hysteroscopic Morcellation With Cold Loop Resectoscopy. PMID- 27678993 TI - Videos and Images of Rare Presentations in Hysteroscopy. PMID- 27678994 TI - The Safety and Value of Local Anaesthetic Protocol in Outpatient Operative Hysteroscopy; Review of 100 Episodes. PMID- 27678995 TI - Gynaecological Procedures and Surgery Under Procedural Sedation and Analgesia (PSA) in a Dutch Out-Patient Clinic. PMID- 27678996 TI - Symptomatic Central Hematometra and Postablation Tubal Sterilization Syndrome (PATSS) After Second Generation Endometrial Ablation. PMID- 27678997 TI - Increase in Prophylactic Salpingectomy Across All Approaches Following an Educational Initiative. PMID- 27678999 TI - Clinical Significance of Office Hysteroscopy in Examination Algorithm of Partly Faulty Uterus Scar After Cesarean Section on the Stage of Pregnancy Planning. PMID- 27678998 TI - Crowdsourcing: A Valid Alternative to Expert Evaluation of Robotic Surgery Skills. PMID- 27679000 TI - Application of Ultrasonography Combined With Hysteroscopy in the Middle and Lower Segment of Intrauterine Adhesions. PMID- 27679001 TI - The Essure Hysteroscopic Sterilization: Initial Experience in Cardiff, UK - Does Prior Contraception Influence the Ease of Device Placement? PMID- 27679002 TI - 3D Sonography and Office Hysteroscopy to Explore Late Fetal Loss. PMID- 27679003 TI - Hysteroscopic Vaginal Septum Resection in Adolescent Girl With Herlyn-Werner Wunderlich Syndrome. PMID- 27679004 TI - Fertility after Myomectomy With the MyoSure(r) Hysteroscopic Tissue Removal System. PMID- 27679006 TI - Profile of Women With Endometrial Polyps Treated in a Tertiary Hospital: Retrospective Chart Review and Review of Literature. PMID- 27679007 TI - Eleven Cases Robert's Uterus Treated by Hysteroscopy and Laparoscopy Successfully Delivered in 1 Case. PMID- 27679005 TI - Endometrial Sampling of the Post-Menopausal Uterus: MyoSure(r) Lite Tissue Removal System vs. Sharp Curettage. PMID- 27679008 TI - Successful Pregnancy Outcome After Hysteroscopic Resection of Endometrial Carcinoma. PMID- 27679009 TI - About Infertility Treatment Issue: Hysteroscopic Polypectomy and Outcome. PMID- 27679010 TI - Successful Treatment of Cesarean Scar Pregnancy by Surgery of Hysteroscopic Resection. PMID- 27679011 TI - Normal Versus Abnormal Tubal Ostia at Hysteroscopy. PMID- 27679012 TI - Significance of Endoscopic and Morphological Methods of Diagnosis for Specification of Female Sterility Variants. PMID- 27679013 TI - The Effectiveness of Laparoendoscopic Single-Site Surgery (LESS) Compared With Conventional Laparoscopic Surgery for Ectopic Pregnancy With Hemoperitoneum. PMID- 27679015 TI - Laparoscopically Guided Transversus Abdominis Plane (TAP) Blocks: Development of a Technique. PMID- 27679014 TI - Morcellation Techniques for Laparoscopic Hysterectomy and Myomectomy: A Retrospective Study. PMID- 27679016 TI - The Usefulness of Mini-Laparoscopic Cystectomy for Small Endometrioma in Adolescent Women. PMID- 27679017 TI - Comparison of NLR Changes After TLH, VH, and TAH. PMID- 27679018 TI - The Importance of the Accurate Diagnostic Preoperational Magnetic Resonance Imaging (MRI) Examinations: Review of 1059 Cases That Undergoing Laparoscopic Surgery for Diagnosed Benign Uterine Myoma. PMID- 27679019 TI - 3-D Transvaginal Sonography as a Preoperative Tool in Predicting the Need to Morcellate in Women Undergoing Laparoscopic Hysterectomy. PMID- 27679020 TI - Single-Port Laparoscopy as a Feasible Technique to Approach Benign Adnexal Mass Surgically. PMID- 27679021 TI - Use of Intravenous Tranexamic Acid During Myomectomy: A Randomized Double-Blind Placebo Controlled Trial. PMID- 27679022 TI - Laparoscopic Abdominal Access Using a Modified Left Upper Quadrant Technique in Morbidly Obese Women Undergoing Gynecologic Surgery. PMID- 27679023 TI - Single-Port Access Laparoscopic Myomectomy Using OctoportTM Access and Suture Technique With Barbed Suture (V-LocTM). PMID- 27679024 TI - The Potential Value of the Haptic Feedback Instrument in Laparoscopic Surgery of Colorectal Carcinomas: A Health Technology Assessment. PMID- 27679025 TI - Predictors of Readmission After Minimally Invasive Gynecologic Surgery. PMID- 27679026 TI - Outcomes After Laparoscopy Microsurgical Tubal Reanastomosis. PMID- 27679027 TI - Patient Awareness of Surgical Procedures in the Preoperative Suite. PMID- 27679028 TI - A Review of Total Laparoscopic Hysterectomy Using ALTRUS(r) Thermal Fusion Tissue System. PMID- 27679029 TI - Laparoscopic Supracervical Hysterectomy or Myomectomy With Power Morcellation: Risk of Uterine Leiomyosarcomas. A Retrospective Trial Including 35.161 Women in Germany. PMID- 27679030 TI - Rates of Minimally Invasive Hysterectomy and Myomectomy Decrease After the FDA Warning on Power Morcellation. PMID- 27679031 TI - Development and Evaluation of a Low-Cost, Reusable Laparoscopic Entry and Emergency Model. PMID- 27679032 TI - Laparoscopic and Robotic Skills Are Transferable in a Simulation Setting. PMID- 27679033 TI - Quality of Life: Single-Port Versus Multi-Port Laparoscopic Surgery for Benign Gynecological Diseases. PMID- 27679034 TI - Latrogenic Parasitic Myomas: The "Real" Long-Term Complication of Laparoscopic Uterine Morcellation. Diagnostic, Management and Preventing Rules. PMID- 27679036 TI - Torsion of Ovarian Leiomyoma in a Woman With 10 Weeks' Gestation. PMID- 27679035 TI - Laparoscopic Cerclage for Prevention of Recurrent Pregnancy Loss Due to Cervical Incompetence. PMID- 27679037 TI - Our experience of Laparoscopic Anterior Exenteration in Locally Advanced Cervical Carcinoma. PMID- 27679038 TI - Concurrent Laparoscopic Vaginal Prolongation by Peritoneum Improves Sexual Satisfaction for Early-Stage Cervical Cancer Patients With Laparoscopic Radical Hysterectomy. PMID- 27679039 TI - Quantification of Safety Risk Factors in Laparoscopic Hysterectomy: A Prospective International Multicentre Study. PMID- 27679041 TI - Combined Preoperative MRI and FDG PET/CT Based Clinical Stage I Disease Is Not Correlate With Postoperative Findings in Laparoscopically Well Staged Low Risk Endometrial Carcinoma Cases. PMID- 27679040 TI - Tru-Cut Biopsy in Gynecologic Surgery. PMID- 27679042 TI - Recent Trends in Robotic and Minimally Invasive Surgery in the Panhandle of Texas Over the Past 5 Years. PMID- 27679043 TI - Five Cases of Cervical Cancer Where Laparoscopic Ovarian Transposition Was Performed Before Pelvic Radiotherapy. PMID- 27679044 TI - Hysterectomy in Women With Previous Cesarean Section: Lateral Dissection Technique for Creation of a Bladder Flap. PMID- 27679045 TI - Pulmonary Recruitment Maneuver for Reducing Postoperative Shoulder Pain Incidence After Laparoscopic Gynecologic Surgery: A Prospective Randomized Controlled Trial. PMID- 27679046 TI - Superior and Inferior Epigastric Vessel Location in the Resting and Insufflated Abdomen. PMID- 27679047 TI - A Prospective Survey of Postoperative Pain and Recovery: A Comparison of Surgical Approaches in Gynecology. PMID- 27679048 TI - Two Phase Laparoendoscopic Single-Site Cervical Ligament-Sparing Hysterectomy: An Initial Experience in a Single Center. PMID- 27679049 TI - Deep Epigastric Vessel Location in the Gravid Abdomen. PMID- 27679050 TI - Single-Port (Grove Port) Laparoscopic Hysterectomy With Extracoporeal Vaginal Cuff Closure Versus Conventional Laparoscopic Hysterectomy With Intracoporeal Vaginal Cuff Closure. PMID- 27679052 TI - Laparoscopic Hysterectomy: Dos and Don'ts. PMID- 27679051 TI - Bean Bag and Shoulder Supports to Prevent Patient Displacement in Gynecologic Laparoscopic Surgery. PMID- 27679054 TI - Cell Salvage in Laparoscopic Surgery for Ectopic Pregnancy With Massive Hemoperitoneum. PMID- 27679053 TI - Contained In-Bag Mechanical Morcellation: Technique and Prospective Case-Series. PMID- 27679055 TI - Retrospective Analysis of 225 Cases Between Ligation of Uterine Arteries and Suturing of Uterine Vessels and Cervical Stump Ligation in Laparoscopic Supracervical Hysterectomy(LSH). PMID- 27679056 TI - Correlation Between the Number of Previous Pelvic Surgeries and Surgical Complications in Patients Undergoing Laparoscopic Hysterectomy. PMID- 27679057 TI - Abdominal Pregnancy - A Constant Location? A Case Report of an Omental Viable Pregnancy and Review of Literature. PMID- 27679058 TI - Laparoscopic Entry in Patients With Previous Surgical History or Complex Pathology. PMID- 27679059 TI - Feasibility and Perioperative Outcomes of Robotic-Assisted Radical Hysterectomy After Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer. PMID- 27679060 TI - Robotic Hysterectomy: The Slowest and Least Cost Effective Route of Minimally Invasive Hysterectomy Even Among High Volume Surgeons. PMID- 27679061 TI - Development of an Educational Robotic Psychomotor Skills Model. PMID- 27679062 TI - Laparoscopic Uterine Cerclage: An Audit of Safety and Reproductive Outcomes. PMID- 27679063 TI - Real Time Haptic Feedback in Endoscopy: The Proof of Concept. PMID- 27679064 TI - Impact of Minimally Invasive Gynecologic Surgery Fellowship Training on Concomitant Levonorgestrel-Releasing Intrauterine Device Placement at the Time of Laparoscopic Surgery. PMID- 27679065 TI - Hybrid Surgical Technique: Single-Site Laparoscopic Myomectomy Using Robotic Assisted Laparoscopic Suture. PMID- 27679066 TI - Role of Laparoscopy and Hysteroscopy in the Evaluation of Uterine Scar After Cesarean Section and Its Surgical Correction. PMID- 27679067 TI - The Efficacy of IV Ferric Carboxymaltose in the Perioperative Management of Moderate to Severe Iron Deficiency Anemia. PMID- 27679068 TI - Feasability and Clinical Outcome With Laparoscopic Management of Extrauterine Pregnancies. PMID- 27679069 TI - Vaginal Cuff Closure With Unidirectional Barbed Suture During Total Laparoscopic Hysterectomy is a Safe and Feasible Procedure. PMID- 27679070 TI - Use of the Articulating Enseal(r) Facilitates Completion of Complex Single Site Laparoscopic Surgery. PMID- 27679071 TI - Laparoscopic Approach to Intrapelvic Nerve Entrapments. PMID- 27679072 TI - Caudal Displacement of the Umbilicus: A Novel Technique for a Safer Veress Needle Intraperitoneal Placement (VIP) During Laparoscopic Entry. PMID- 27679073 TI - An Easy and Safe Approach to the Minimally Invasive Laparoscopic Treatment of Dermoid Cysts: The Mimic Laparoscopic Surgery With Bathtub Method. PMID- 27679074 TI - Degenerating Fibroid Mimics Malignancy. PMID- 27679075 TI - Single-Site Laparoscopy for Management of Perforated Intrauterine Device With Small Bowel Mesentery Implantation. PMID- 27679076 TI - Laparoscopic Hysterectomy Intrafascial (LHi) Following Pelvic Vein Embolization With Coils. PMID- 27679077 TI - The Familiarity With Laparoscopic Instruments Costs Among Obstetrics & Gynaecology Trainees in Wales, UK. PMID- 27679079 TI - Pathway of Enhanced Recovery for Total Laparoscopic Hysterectomy, Pilot Study of 50 Cases. PMID- 27679078 TI - Disseminated Peritoneal Leiomyomatosis After Open Power Morcellation: A Case Report. PMID- 27679080 TI - Unusual Large Parasitic Leiomyoma in a 29-Year-Old Nulligravida Requiring Bowel Resection. PMID- 27679082 TI - An Attempt to Prevent Vaginal Stump Infection After Total Laparoscopic Hysterectomy. PMID- 27679081 TI - Laparoscopic Treatment of Ovarian Torsion in Ovarian Hyperstimulation Syndrome in Pregnancy. PMID- 27679083 TI - Use of 3-0 V-Loc(r) Suture for Vaginal Cuff Closure in Laparoscopic Hysterectomy: Single Center Experience. PMID- 27679084 TI - Step Up from Salpingo-Oophorectomy to Total Laparoscopic Hysterectomy Incorporating Incision Dissectiong Procedures. PMID- 27679085 TI - In-Bag Morcellation: Is the Patient Left Holding the Bag? PMID- 27679086 TI - Laparoscopic Management of a Huge Retro-Cervical Myoma. PMID- 27679087 TI - Should In-Bag Morcellation Be Considered During Laparoscopic Myomectomy in the Chinese Population? PMID- 27679088 TI - Ectopic Pregnancy Repeated in Caesarean Scar. A Case Report. PMID- 27679089 TI - Establishment of Minimally Invasive Hysterectomy Option for Women at a Regional Hospital in New Zealand. PMID- 27679090 TI - Surgical Management and Obstetric Outcomes of Laparoscopic Adnexal Surgery in Pregnancy. PMID- 27679091 TI - Comparison of Robotics Versus Conventional Laparoscopy for Management of Benign Adnexal Masses. PMID- 27679092 TI - False-Positive Cystoscopic Diagnosis of Ureteral Obstruction After Hysterectomy Due to a Non-Functional Kidney. PMID- 27679093 TI - A Case Series of Benign Cystic Mesothelioma as a Rare Etiology of Ascites. PMID- 27679094 TI - Introduction of a Novel Approach to Maintaining Pneumoperitoneum at Total Laparoscopic Hysterectomy (TLH). PMID- 27679095 TI - Total Laparoscopic Hysterectomy (TLH): A Holly Grail or a Harbinger of Trouble? PMID- 27679096 TI - How to Avoid Laparotomy Doing Laparoscopic Hysterectomy. PMID- 27679097 TI - Abdominal Wall Lymphocele Following Gynecologic Surgery: A Case Report and Literature Review. PMID- 27679098 TI - Minimally Invasive Surgery for Schwannomas of Female Genitalia. PMID- 27679099 TI - Laparoscopic View of a Case of Incomplete Uterine Inversion After Vaginal Delivery. PMID- 27679100 TI - Lateral Approach to Laparoscopic Uterine Artery Ligation Previous to Laparoscopic Hysterectomy: The Anatomy of the Bermuda Triangle. PMID- 27679101 TI - Abnormal Ureteral Position With Adherant Ovary. PMID- 27679102 TI - Single Site Total Laparoscopic Hysterectomy for Huge Uterus With Large Myoma. A Case Report. PMID- 27679104 TI - Novel Device for Targeting Tumors in Laparoscopic Radiofrequency Ablation: A Learning Curve Study. PMID- 27679103 TI - Mature Cystic Teratoma Is a Good Indication for LESS Approach: Initial Experience of an Internal Organ Retractor (IOR) device or Barbed Suture for LESS Cystectomy. PMID- 27679105 TI - Less-Invasive or Minimally-Invasive: Does it Really Matter? PMID- 27679106 TI - The Introduction of "Mini-Touch" Microwave Endometrial Ablation in an Outpatient Setting in a UK District General Hospital. PMID- 27679107 TI - Utility of PKS Omni(r) Electrosurgical Device in Laparoscopic Hysterectomy. PMID- 27679108 TI - Office Hysteroscopy, a 21st Century Technology Applied to a Developing Country in Latin America. PMID- 27679109 TI - A New Reduced-Port Laparoscopic Technique and Use of a Newly Developed 5-mm Retrieval Bag and New 2.4-mm Tapering Forceps. PMID- 27679110 TI - Transcutaneous Temperature Controlled Radiofrequency for Atrophic Vaginitis and Dyspareunia. PMID- 27679111 TI - Comparing Safety and Efficacy of Zip-StitchTM Versus Absorbable Suture in Closing the Vaginal Cuff after Laparoscopic Hysterectomy in the Porcine Model. PMID- 27679112 TI - Haptic Feedback in Laparoscopic Surgery: The Surgeons' Perspective. PMID- 27679113 TI - Laparoscopic Myomectomy After Uterine Artery Clipping at the Origin in Selected Cases Reduces Blood Loss - A Case Series. PMID- 27679114 TI - Outcomes of Endometrial Cancer Patients at Risk of Lymph Node Metastasis With Para-Aortic Lymphadenectomy Below the Level of Inferior Mesenteric Artery. PMID- 27679115 TI - Laparoscopic Restaging Surgery in Patients With Unexpected Uterine Cancer. PMID- 27679116 TI - A Comparative Study of Preoperative Findings and Outcomes in Pre-Menopausal and Post-Menopausal Women With Leiomyosarcoma. PMID- 27679117 TI - A Detailed Analysis of the Learning Curve: Da Vinci Robot-Assisted Radical Hysterectomy in Cervical Cancer. PMID- 27679118 TI - Clinical Outcomes of Type II Endometrial Cancer in Open Versus Minimally Invasive Staging Surgery. PMID- 27679119 TI - A Comparative Study of the Methods of Diagnosis and Outcomes of Different Uterine Sarcoma Types. PMID- 27679120 TI - Comparison of Clinical Outcomes of Bovie Blade Versus Cold Knife Conization as a Treatment Modality of High-Grade Cervical Intraepithelial Neoplasia. PMID- 27679121 TI - Learning Curve Analysis of Robot-Assisted Total Laparoscopic Hysterectomy in a Gynecologic Oncology Practice at Winthrop University Hospital. PMID- 27679122 TI - Laparoscopic Lymphadenectomy for Gynecologic Malignancies: Evaluation of the Surgical Approach and Outcomes Over a Seven Year Experience. PMID- 27679123 TI - Robot-Assisted Vulvectomy and Bilateral Inguinofemoral Lymphadenectomy in Patients With Stage I/II Squamous Cell Vulval Carcinoma: Farghaly's Technique. PMID- 27679124 TI - Treatment Outcome of Patients With Early Stage Cervical Cancer Treated With Laparotomy Compared to Robotically-Assisted Laparoscopic Approach. PMID- 27679125 TI - Extrafascial Hysterectomy Without Preoperative Conization is Unacceptable in Patients With Adenocarcinoma in Situ Diagnosed by Cervical Punch Biopsy or Endocervical Curettage. PMID- 27679126 TI - Development of Uterine Smooth Muscle Tumour of Uncertain Malignant Potential (STUMP) After Laparoscopic Myomectomy of an Atypical Leiomyoma. PMID- 27679127 TI - Laparoscopic Technique for Central Early Stage Recurrent Cervical Cancer. PMID- 27679128 TI - Incidental Small Ovarian Surface Serous Carcinoma With Miliary Abdominal Seeding During Robotic-Assisted Total Hysterectomy. PMID- 27679129 TI - Pathologic Findings in Women Undergoing Hysterectomy for Pelvic Pain. PMID- 27679130 TI - Characteristics of Women Undergoing Hysterectomy for Chronic Pelvic Pain: Prevalence and Risk Factors for Endometriosis. PMID- 27679131 TI - Impact of Different Approaches of Colpopexy on Pelvic Pain. PMID- 27679132 TI - Internet Research Effects on Patient Familiarity With and Perceptions of Fibroid Treatments. PMID- 27679133 TI - Use of Laparoscopy in Unexplained Infertility in Historically Underserved Area. PMID- 27679135 TI - Predictors of Hemorrhage and Transfusion for Women Undergoing Laparoscopic and Robotic-Assisted Myomectomy. PMID- 27679134 TI - Unidirectional Knotless Barbed Suture for Laparoscopic Myomectomy: Fertility, Pregnancy and Delivery Outcomes. PMID- 27679137 TI - The Role of beta hCG Increment in the 48 Hours Prior to Methotrexate Treatment as a Predictor for Treatment Success. PMID- 27679136 TI - Reproductive Surgery Female Genital Anomalies. PMID- 27679138 TI - The Expression of the Proliferation Marker Ki-67 Tissue of the Uterine Fibroids and Fiber Adhesions in Patients With Uterine Fibroids in Reproductive Age. PMID- 27679139 TI - Uterine Artery Embolization (UAE) for Uterine Arteriovenous Malformation (AVM) in 5 Women Desiring Fertility: Pregnancy Outcomes. PMID- 27679140 TI - Laparoscopic Myomectomy: A 6-Year Experience at Nordica Fertility Center, Lagos, Nigeria. PMID- 27679141 TI - Robotic Abdominal Cerclage: A Case Series with Pregnancy Outcomes. PMID- 27679142 TI - Intraoperative Monitoring and Evaluation of MRI in Women of Reproductive Age After Previously Performed Uterine Artery Embolization (UAE) and MRgFUS Ablation of Fibroids. PMID- 27679143 TI - Reproductive Outcomes After Fertility-Sparing Surgery and Postoperative Adjuvant Chemotherapy in Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors. PMID- 27679144 TI - Surgical Treatment for Adnexal Masses in Pregnant Women. PMID- 27679145 TI - Normal Pregnancy Outcome After Transcervical Radiofrequency Ablation of Uterine Fibroids. PMID- 27679146 TI - Reproductive Outcomes in Subjects Following Radiofrequency Volumetric Thermal Ablation (RFVTA) of Their Symptomatic Myomas: A Retrospective Case Series. PMID- 27679147 TI - The Use of Vaginal Mold Following Resection of Transverse Vaginal Septum as Treatment Approach to Patient With Multiple Failed Attempts to Resolve Recurrent Hematocolpos. PMID- 27679148 TI - Comparison of Robotic Vs. Laparoscopic Needle Throw for Maiden Surgical User. PMID- 27679149 TI - Can Tubal Flushing With Hysterosalpingo-Foam Sonography (HyFoSy) Media Increase Women's Chances of Pregnancy? PMID- 27679150 TI - Comparison of Perioperative Complications Between of Robotics and Laparoscopy Approaches in the Management of Gynecologic Malignances. PMID- 27679151 TI - Detection of Sentinel Lymph Node Mapping Using Indocyanine Green in the Management of Endometrial Cancer: A Pilot Study. PMID- 27679152 TI - Assessment of Long-Term Urinary Symptoms and Quality of Life After Robotic Assisted Sacrocolpopexy With or Without Concomitant Midurethral Sling. PMID- 27679153 TI - Comparison of Robotics, Laparoscopy and Laparotomy in the Management of Recurrent Ovarian Cancer. PMID- 27679154 TI - Perioperative Complications of Robotic-Assisted Laparoscopic Surgery at a Single Institution. PMID- 27679155 TI - Successfully Removed Unfavorably Located Myomas By Robot-Assisted Laparoscopic Myomectomy. PMID- 27679156 TI - A Novel 2-Port Robotic Myomectomy. PMID- 27679158 TI - Alternative to Power Morcellation. PMID- 27679157 TI - Pregnancy Outcomes and Symptom Relief Following Robot-Assisted Laparoscopic Myomectomy (RALM): A Patient Survey Study With Clinical Correlation. PMID- 27679159 TI - Establishing the Feasibility of Robot-Assisted Hysterectomy as an Outpatient Procedure in a Community Setting. PMID- 27679160 TI - Non-Cutaneous Melanomas of the Genital Tract: Minimally Invasive Robotic Treatment of Primary Vaginal Melanoma-Case Report. PMID- 27679161 TI - Comparison of Robotic-Assisted and Abdominal Hysterectomy with Concomitant Burch Colposuspension: Preluminary Study. PMID- 27679162 TI - Step-Wise Surgical Approach for Placement of a Robotic-Assisted Transabdominal Cervical Cerclage in the Non-Pregnant Patient. PMID- 27679164 TI - The Impact of Procedure Setting on Two-Year Outcomes for the Altis Single Incision Sling for Women With Stress Urinary Incontinence. PMID- 27679163 TI - Operative Morbidity in Patients Undergoing Hydrodissection With Epinephrine During Surgery for Pelvic Organ Prolapse IIAP, IIIC AND IVCE IIAP, IIIC and IVC. PMID- 27679165 TI - Efficacy and Safety of Solifenacin Succinate Tablets Versus Solifenacin Succinate Tablets With Local Oestrogen for Overactive Bladder in Post-Menopausal Women - A Multi-Centre, Randomised, Open, Controlled Comparison Study. PMID- 27679166 TI - Complications Following Outside-In and Inside-Out Transobturator-Tape Procedures With Concomitant Gynecologic Operations. PMID- 27679167 TI - Occult Malignancy in Women Undergoing Hysterectomy for Pelvic Organ Prolapse. PMID- 27679168 TI - Treatment of Bladder Pain Syndrome and Interstitial Cystitis: A Systematic Review. PMID- 27679170 TI - Comparison of the Clinical and Functional Outcomes After the Inside-Out TVT-O Procedure With or Without Concomitant Transvaginal Gynaecological Surgery. PMID- 27679169 TI - Long-Term Outcomes of the Self-Cut Mesh-Related Modified Total Pelvic Reconstructive Surgical Repair for Pelvic Organ Prolapse in China: A 7-Year Prospective Cohort Study. PMID- 27679171 TI - Predicting Post-Operative Urinary Retention (PUR) in Women Undergoing Pelvic Reconstructive Surgery. PMID- 27679172 TI - Natural Orifice Sacral Colpopexy: A New Approach to a Time-Honored Procedure. PMID- 27679173 TI - Predictors of Length of Stay After Vaginal Hysterectomy. PMID- 27679174 TI - In Office Single Incision Sling Procedure: A Safe, Cost-Effective Approach for the Surgical Management of Stress Urinary Incontinence. PMID- 27679175 TI - Mid-Term Experience With Elevate-PC Prolapse Repair Systems. PMID- 27679176 TI - Transvaginal Trigger Point Injections for Pelvic Floor Myofascial Spasm: A Retrospective Review of Pain Assessment and Development of a Treatment Algorithm. PMID- 27679177 TI - Squamous Cell Carcinoma in a Urethral Caruncle. PMID- 27679178 TI - Comparing the Midterm Outcome of Single Incision Vaginal Mesh and Transobturator Vaginal Mesh in Treating Severe Pelvic Organ Prolapse. PMID- 27679179 TI - Prevalence of Silent Voiding Dysfunction in Morbidly Obese Women Before and After Bariatric Surgery. PMID- 27679180 TI - Redo Modified Laparoscopic Colposuspension. PMID- 27679181 TI - Evaluation of Vaginal Vault Position With Dynamic MRI in Women Who Had Laparoscopic Sacrocolpopexy for Uterine Prolapse. PMID- 27679182 TI - Device for Safely Removing a Placed Mesh for Pelvic Organ Prolapse. PMID- 27679183 TI - Association Between Patient's BMI and Uterine Weight With Feasibility of Single Port Robotic-Assisted Surgery in Benign Gynecology. PMID- 27679184 TI - Risk of Recurrence of Myomas Following Robotic-Assisted Laparoscopic Myomectomy. PMID- 27679185 TI - Treatment of First Trimester Tubal Ectopic Pregnancy Through Posterior Colpotomy: Residents Can Easily Do It. PMID- 27679186 TI - Development and Validation of a Laparoscopic Vaginal Cuff Closure Simulation Model. PMID- 27679187 TI - Adnexal Torsion in Postmenopausal Women: Clinical Presentation and Risk of Malignancy. PMID- 27679188 TI - Effect of Instituting a Laparoscopic Curriculum on Laparoscopic Knowledge for Ob/Gyn Residents. PMID- 27679189 TI - Renal Calyceal Rupture in a Patient With Early Stage Cervical Carcinoma Treated by Robot-Assisted Radical Hysterectomy and Pelvic Node Dissection. PMID- 27679190 TI - A Theory of Eu-estrogenemia: A Physiological Justification for Optimal Estrogen Receptor Function Via Hormone Replacement Therapy. PMID- 27679191 TI - Development and Validation of a Preoperative Ultrasound Staging System for Predicting Level of Laparoscopic Endometriosis Surgery Required. PMID- 27679192 TI - Is Decreased Insufflation Pressure During Major Robotic-Assisted Gynecologic Surgery Associated With Decreased Recovery Time and Patient Reported Pain Score. PMID- 27679193 TI - Transvaginal Ultrasound Soft Markers for the Prediction of Endometriosis Type and Location in Women Undergoing Laparoscopy. PMID- 27679194 TI - Computed Tomographic Colonography in the Diagnosis of Recto-Sigmoid Endometriosis: A Pilot Study. PMID- 27679196 TI - Graves' Disease Is Associated With Endometriosis: 3-Year Population-Based Study. PMID- 27679195 TI - Ability of MRI and Ultrasound with Multidisciplinary Meeting to Pre Operatively Predict the Need for Bowel Resection. PMID- 27679197 TI - Risk of Occult Uterine Sarcoma in Women Undergoing Hysterectomy for Benign Indications. PMID- 27679198 TI - Lysis of Anterior Abdominal Wall Adhesions: A Systematic Approach. PMID- 27679199 TI - Fascial Anatomy and Its Relevance in Safe Laparoscopic Hysterectomy. PMID- 27679200 TI - Predictive Factors for Reoperation in Patients Surgically Treated for Endometriosis. PMID- 27679201 TI - Uterine Endometriosis - Incidence in Patients Undergoing Laparoscopic Surgery for Severe Recto-Vaginal Endometriosis. A Prospective Cohort Study. PMID- 27679202 TI - Incidental Appendectomy in the Surgical Treatment of Deep Endometriosis Infiltrating the Bowel: Anatomopathological Findings in a Series of 109 Patients. PMID- 27679204 TI - Laparoscopic Vascular Injury Simulation for Gynecology Residents. PMID- 27679203 TI - Comparative Analysis of Chemokines and Cytokines in Women With Epithelial Ovarian Cancer (EOC) and Endometriomas. PMID- 27679205 TI - Simulating Vaginal Cuff Closure for Ob/Gyn Residents Learning Laparoscopic Hysterectomy. PMID- 27679206 TI - Interest of Complex Tasks on Laparoscopic Virtual Reality Simulator: A Prospective Randomized Study Among Naive Medical Students. PMID- 27679207 TI - Impact of Implementing a Simulation Lab in a Teaching Institution on Outcome of Hysterectomy. PMID- 27679208 TI - A New Virtual Reality Training Module for Laparoscopic Surgical Skills and Equipment Handling: Can Multitasking Be Trained? A Randomized Controlled Trial. PMID- 27679209 TI - Simulation Based Robotics Training to Test Skill Acquisition and Retention. PMID- 27679210 TI - Trainee Perception of Uterine Morcellation: The University of Chicago Resident Experience. PMID- 27679211 TI - Development of a Low Fidelity Model to Teach Laparoscopic Salpingostomy and Salpingectomy. PMID- 27679212 TI - Warm-Up Before Robotic Hysterectomy Does Not Improve Trainee Operative Performance: A Randomized Trial. PMID- 27679213 TI - Impact of a Minimally Invasive Gynecologic Surgeon on Patient Outcomes Following Laparoscopic Hysterectomy. PMID- 27679214 TI - Incidence of Uterine Sarcoma in 1432 Consecutive Minimally Invasive Hysterectomies. PMID- 27679215 TI - The Role of Ethnicity in the Treatment of Uterine Fibroids With Ulipristal Acetate. PMID- 27679216 TI - The Incidence of Uterine Cancer Among Women Undergoing Hysterectomy for Benign Disease. PMID- 27679217 TI - Women's Knowledge and Perceptions of Morcellation. PMID- 27679218 TI - Three-Dimensional Vision: Does It Improve Acquisition of Laparoscopic Skills? PMID- 27679219 TI - Comparison of Robotic Versus Laparoscopic Metroplasty for Uterine Scar Defect. PMID- 27679220 TI - Comparison of Laparoscopically Assisted Transversus Abdominis Plane Block Using Liposomal Bupivacaine With Pre-Incisional Bupivacaine for Post-Operative Pain Control in Patients Undergoing Laparoscopic or Robotic-Assisted Laparoscopic Hysterectomy: A Randomized Controlled Trial. PMID- 27679221 TI - Estimating Incidence of Leiomyosarcoma After Minimally Invasive Supracervical Hysterectomy and Myomectomy: Retrospective Cohort Study. PMID- 27679222 TI - The Use of Antibiotics in Gynecological Endoscopy. A Randomized, Double-Blind, Placebo-Controlled Trial. PMID- 27679223 TI - Postoperative Incisional Bupivacaine in Gynecologic Laparoscopy: A Randomized Controlled Trial. PMID- 27679224 TI - Feasibility and Safety of a Minimally Invasive Surgical (MIS) Approach in Complex Myomectomies. PMID- 27679225 TI - Three-Dimensional Versus Two-Dimensional Radical Laparoscopic Hysterectomy for Endometrial and Cervical Cancer: A Prospective Randomized Trial. PMID- 27679226 TI - Single Port Transumbilical Laparoscopic Surgery Versus Conventional Laparoscopic Surgery for Adnexal Lesions: ASingle Center Experience in China. PMID- 27679227 TI - Vasopressin Administration During Laparoscopic Myomectomy: A Randomized Controlled Trial. PMID- 27679228 TI - Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long Term Follow-Up of a Prospective Randomized Trial. PMID- 27679229 TI - The Outcome of Laparoscopy Versus Laparotomy for the Management of Early Stage Cervical Cancer-Meta Analysis. PMID- 27679230 TI - Sentinel Node Mapping in Endometrial Cancer By Using Hysteroscopic Injection of Indocyanine Green and Laparoscopic Near-Infrared Fluorescence Imaging: A Preliminary Experience. PMID- 27679231 TI - Impact of MRI and a Comprehensive Strategy on a Continuous Cohort of 3056 Patients Referred for Fibroids to Diagnose Sarcomas. PMID- 27679233 TI - Trends in Route of Hysterectomy Associated With the Implementation of a Comprehensive Robotics Training Program at a Large Teaching Hospital and as Compared to a Smaller Community Hospital Over a 5-Year Period. PMID- 27679232 TI - Incidence and Prevention of Vaginal Cuff Dehiscence Following Laparoscopic and Robotic Hysterectomy: A Systematic Review and Meta-Analysis. PMID- 27679235 TI - The SONATA Study: Sonography-Guided Transcervical Ablation of Uterine Fibroids. PMID- 27679234 TI - Early Clinical Response to Intrauterine Ultrasound-Guided Transcervical Radiofrequency Ablation. PMID- 27679236 TI - Face- and Content Validity of a New Portable Tablet Box Trainer for Training Laparoscopic Skills at Home. PMID- 27679237 TI - Single-Port Laparoscopically Assisted-Transumbilical Ultraminilaparotomic Myomectomy (SPLA-TUM) Versus Single Port Laparoscopic Myomectomy: A Randomized Controlled Trial. PMID- 27679238 TI - Correlation of Reductions in Perfused Fibroid Volume With Subsequent Reductions in Total Fibroid Volume After Transcervical Radiofrequency Ablation. PMID- 27679239 TI - Development of a Low Cost, Medium Fidelity Hysteroscopy Simulator for Spatial Orientation Training: Proof of Concept. PMID- 27679241 TI - Intraoperative Transvesical Ultrasound as an Alternative to Cystoscopy to Assess Ureteral Patency. PMID- 27679240 TI - Use of a Novel, Cordless Ultrasonic Dissector for Gynecologic Minimally Invasive Surgical Procedures. PMID- 27679242 TI - The Use of Inflammatory Cytokine Levels as a Measure of Symptom Distress and Quality of Life in Patients With Overactive Bladder. PMID- 27679243 TI - The Six View Hysterectomy: An Inanimate Model and Systematic Approach to Learning Uterine Manipulation and Exposure at the Time of Laparoscopic and Robotic Hysterectomy. PMID- 27679244 TI - Cervical Priming Prior to Operative Hysteroscopy: A Randomized Controlled Study Comparing the Efficacy of Laminaria Versus Evening Primrose Oil (EPO). PMID- 27679245 TI - Prospective Study on the of Use of the MyoSure(r) for Hysteroscopic Resection of Endometrial Pathology. PMID- 27679246 TI - Combining Paracervical Block With a Complete Fundal Block Significantly Reduces Patients' Perception of Pain During Radio-Frequency Endometrial Ablation in an Office Setting. PMID- 27679247 TI - Application of Narrow-Band Imaging Hysteroscopy in the Diagnosis of Endometrial Lesions. PMID- 27679248 TI - Final Results of a Multicenter Trial of Safety and Effectiveness of Endometrial Ablation With the AEGEA Vapor System for the Treatment of Menorrhagia. PMID- 27679249 TI - Endometrial Ablation With the AEGEA Vapor System in Challenging Uterine Anatomies. PMID- 27679250 TI - Saline Contrast Sonohysterography for the Diagnosis of Cesarean Scar Defect. PMID- 27679251 TI - Hysteroscopic Evacuation of Retained Products of Conception: Two Case Reports and a Systematic Literature Review. PMID- 27679252 TI - Safety and Efficacy of Distending Media Infusion by Manual Syringe Method for Hysteroscopic Procedures: A Retrospective Analysis. PMID- 27679253 TI - A Comparative Study of Clinical Characteristics and Preoperative Findings of Different Sarcoma Types. PMID- 27679254 TI - Comparison of Robotic Vs Laparoscopic or Open Radical Hysterectomy: Five Year Survival for Surgical Treatment for Clinic Stage I Cervical Cancer. PMID- 27679255 TI - A Comparison Between Laparotomy, Laparoscopy and Robotic-Assisted Radical Hysterectomy in Surgical Treatment of Early Stage Cervical Cancer. PMID- 27679256 TI - Early Stage Uterine Serous Carcinoma: Does Surgical Approach Impact Survival? PMID- 27679257 TI - The Adoption of Single-Port Laparoscopic Full Staging for Endometrial Cancer: Safety, Learning Curve and Surgical Outcome. PMID- 27679258 TI - Feasibility of Robotic Laparoendoscopic Single Site Surgery in the Gynecologic Oncology Setting. PMID- 27679259 TI - Accuracy of Hysteroscopic Metroplasty With the Combination of Pre Surgical Three Dimensional Ultrasonography and a Novel Graduated Intrauterine Palpator: A Randomized Controlled Trial. PMID- 27679260 TI - A Single Injection of Depomedroxyprogesterone Acetate (Dmpa) Immediately After Rollerball Endometrial Ablation Significantly Improves Clinical Outcomes in Women With Heavy Menstrual Bleeding. PMID- 27679261 TI - Reduced Port Size Nerve Sparing Radical Trachelectomy- The Least Invasive Fertility Sparing Radical Surgery. PMID- 27679262 TI - Robotic Dissection of a Retroperitoneal Ovarian Neoplasm. PMID- 27679263 TI - A Retrospective Descriptive Comparison Study of Transvaginal Ultrasound Scan Findings With Histology Findings on Postmenopausal Women Who Underwent Hysteroscopy for Endometrial Assessment. PMID- 27679264 TI - Uterine Leiomyosarcoma: Experience From an Ethnically Diverse Tertiary Care Referral Center. PMID- 27679265 TI - Suspected Vs. Unsuspected Uterine Leiomyosarcoma: Lessons From an Ethnically Diverse Tertiary Care Referral Center. PMID- 27679266 TI - Abdominal Wall Endometriosis: A Multidisciplinary Approach. PMID- 27679267 TI - 17beta-Estradiol Induces Over-Proliferation in Adenomyotic Human Uterine Smooth Muscle Cells of the Junctional Zone Through Hyper-Activation of the Estrogen Receptor-Enhanced RhoA/ROCK Signaling Pathway. PMID- 27679268 TI - Role of Gluten-Free Diet in the Management of Chronic Pelvic Pain of Deep Infiltranting Endometriosis. PMID- 27679269 TI - Accuracy of Magnetic Resonance Imaging (MRI) in the Diagnosis of Endometriosis - Evaluation of an Institutional Protocol. PMID- 27679270 TI - Histological Findings Following Excision of Peritoneal Endometriosis With and Without Using Aqua Blue Contrast Technique (ABCtTM). PMID- 27679271 TI - Rare Association Between Inguinal and Umbilical Endometriosis in a Patient Without Previous Surgery. PMID- 27679272 TI - Laparoscopic Bowel Segmental Resection in the Treatment of Bowel Endometriosis: Safety and Efficiencyy. PMID- 27679273 TI - Surgical Management of Endometriosis: Reoperation Rates Using Multimodal and Multidisciplinary Management Techniques, An Interim Analysis. PMID- 27679274 TI - A Comparison of Examination and Surgical Findings in Women With Endometriosis. PMID- 27679275 TI - Correlation Between Magnetic Resonance Imaging Results and Findings at Surgery for Cases of Severe Endometriosis. PMID- 27679276 TI - Analysis of Risk Factors for Post-Operative Rectovaginal Fistula in Deep Endometriosis. PMID- 27679277 TI - Needle Based Confocal Endomicroscopy (nCLE) Performed Through Transrectal Ultrasound (TRUS): The First Experience in Intestinal Endometriosis. PMID- 27679278 TI - The Impact of Laparoscopic Surgical Management of Deep Endometriosis on Fertility Outcome. PMID- 27679279 TI - Comparison of Complete and Incomplete Excision of Deep Infiltrating Endometriosis. PMID- 27679280 TI - Surgical Outcomes of Laparoscopic Hand-Assisted Hysterectomy Compared to Traditional Open Hysterectomy for Large Uteri. PMID- 27679281 TI - Unsuspected Uterine Sarcoma in an Urban Hospital: Does Surgical Approach Matter? PMID- 27679282 TI - A Cost-Effectiveness Analysis of Morcellation Hysterectomy for Fibroids. PMID- 27679283 TI - Laparoscopic Access Device Injuries: An Analysis of 10 years of Reports to the FDA. PMID- 27679284 TI - Contained Manual Specimen Removal Versus Uncontained Power Morcellation in Laparoscopic Myomectomy. PMID- 27679285 TI - Identifying Risk Factors for Urinar y Retention After Hysterectomy for Leiomyoma. PMID- 27679286 TI - Hysteroscopic Management of a Stenotic Cervix. PMID- 27679287 TI - Hysteroscopic Metroplasty in Women With Unexplained Primary Infertility: A Prospective Cohort Study. PMID- 27679288 TI - Complications and Compliance of Hysteroscopic Sterilization With Essure in an Inner City Hospital. PMID- 27679289 TI - Comparison of Shoulder Pain Reducing Techniques After Laparoscopy and Laparoscopy Assisted Robotic Surgeries. PMID- 27679290 TI - Power Morcellation in Fibroid Surgery: Do Risks Outweigh Benefits? The Patient's Perspective. PMID- 27679291 TI - Incidence of Venous Thrombotic Events Following Gynecologic Surgery. PMID- 27679292 TI - Risk Factors for Conversion of Laparoscopic Hysterectomy. PMID- 27679293 TI - Laparoscopic Myomectomy as a New Standard: An Analysis of Risk Factors for Conversion. PMID- 27679294 TI - A Comparative Study of Minimally Invasive Versus Open Hysterectomy for Women With Fibroid Uterus - A Nationwide Study of 65,216 Patients. PMID- 27679295 TI - Laparoscopic Uterine Retrieval With Preservation of Uterine Vascular Pedicles: Promising Application for Human Uterine Transplants. PMID- 27679296 TI - Peritoneal Washings After Power Morcellation in Laparoscopic Myomectomy: A Pilot Study. PMID- 27679297 TI - Surgical Outcomes of Paravaginal Repair Following Robotic Sacrocolpopexy. PMID- 27679298 TI - Urinary Tract Infection After Mid-urethral Sling. PMID- 27679299 TI - Baseline Understanding of Urinary Incontinence (UI) and Prolapse (POP) in New FPMRS Patients: Is There an Age-Related Difference? PMID- 27679300 TI - Evaluation of 2d Pelvic MRI Measurements as Clinical Predictors of Surgical Failure After Laparoscopic Uterosacral Ligament Suspension. PMID- 27679301 TI - Long-Term Abdominopelvic Surgical Morbidity After Abdominal Vs. Minimally Invasive Hysterectomy With Ovarian Conservation: A Population-Based Cohort Study. PMID- 27679302 TI - Uterosacral Ligament Suspension Complications Between Laparoscopic and Transvaginal Approaches. PMID- 27679303 TI - Transvaginal Hysterectomy With and Without Laparoscopic Assistance Is Associated With Improved Surgical Outcomes Compared to Abdominal and Robotic-Assisted Hysterectomy When Performed for Benign Indications on Large Uteri. PMID- 27679304 TI - Comparing the Clinical Outcome of Transobturator Sling (Monarc(r)) and Single Incision Sling (MiniArc(r)). PMID- 27679306 TI - Association Between Lower Urinary Tract Symptoms and Endometriosis Before and After Laparoscopy. PMID- 27679305 TI - Outcomes of Hybrid Laparoscopoc Sacrocolpopexy for Pelvic Organ Prolapse With Severe Cystocele. PMID- 27679307 TI - Laparoscopic Sacrocolpopexy With a Vaginal Prosthetic Adhesive. PMID- 27679309 TI - A Cost-Effective Approach in Gynecologic Robotic Surgery. PMID- 27679308 TI - Outcomes Following Combined Laparoscopic Burch Urethropexy at Time of Mesh Sling Removal: A Prospective Cohort Study. PMID- 27679310 TI - Posterior Vaginal Supracervical Hysterectomy: No Morcelment. PMID- 27679311 TI - Association of Matrix Metalloproteinase-10 Polymorphisms With the Susceptibility to Pelvic Organ Prolapse. PMID- 27679312 TI - Preoperative Uterine Volume: Does It Predict Symptomatic Fibroid Recurrence After Robotic Myomectomy: A Retrospective Cohort Study. PMID- 27679313 TI - Novel Use of Indocyanine Green for Intraoperative, Real-time Localization of Ureter During Robot-Assisted Excision of Endometriosis. PMID- 27679314 TI - Standard Versus Robot-Assisted Laparoscopic Hysterectomy: A Prospective Randomized Trial. PMID- 27679315 TI - Comparison of Operative and Peri-Operative Results for Robotic and Laparoscopic Myomectomies. PMID- 27679316 TI - Hysteroscopic Removal of Retained Placental Tissue Allieviates Postpartum Hypertension. PMID- 27679317 TI - Robot-Assisted Laparoscopic Adenomyomectomy: Successful Treatment of Adenomyosis Patients Who Wish Uterus-Sparing Treatment. PMID- 27679319 TI - Trans Cockpit Authority Gradient and Dual Robotic Platform Intraoperative Handoffs: A New Evaluation of Teacher and Learner Comfort and Patient Safety. PMID- 27679318 TI - Perioperative Outcomes and Complications of Robot-Assisted Laparoscopic Myomectomy (RALM). PMID- 27679320 TI - Robot-Assisted Laparoscopic Myomectomy, an Alternative to Laparotomy for Numerous Myomas (Over 10). PMID- 27679321 TI - A Comparison of Robot-Assisted Laparoscopic Myomectomy (RALM) With Laparoscopic Assisted Myomectomy (LAM). PMID- 27679322 TI - Hospital Outcomes of Robotic Versus Laparoscopic Hysterectomy: A Texas Statewide Analysis. PMID- 27679323 TI - The Association Between Surgically-Diagnosed Endometriosis and Adverse Pregnancy Outcomes. PMID- 27679324 TI - Fertility and Pregnancy Outcomes Following Robotic Myomectomy. PMID- 27679325 TI - The Selective Progesterone Receptor Modulator, Ulipristal Acetate, in the Management of Symptomatic Uterine Fibroids. PMID- 27679326 TI - Dysmorphic Uterine Congenital Anomalies: A New Lateral Angle and a Cavity Width Ratio on 3D Ultrasound Coronal Section to Define Uterine Morphology. PMID- 27679327 TI - The Effect of Fertility on Resection Margin in Conization. PMID- 27679328 TI - Menstrual Abnormalities and Reproductive Challenges in Women With End Stage Renal Disease on Chronic Dialysis. PMID- 27679329 TI - Haptic Feedback in Laparoscopic Graspers Leads to Tremendous Force Reduction. PMID- 27679331 TI - Laparoscopic Abdominal Cerclage: Patient Selection for Successful Pregnancy Outcomes. PMID- 27679330 TI - The Impact of Salpingectomy for Ectopic Pregnancy on Ovarian Reserve. PMID- 27679332 TI - Trend of Use of Adhesion Barrier During Hysterectomy or Myomectomy and Its Clinical Impact. PMID- 27679333 TI - The Utility of the Transverse Abdominus Plane (TAP) Block in Minimally Invasive Gynecologic Surgery: A Randomized Double Blinded Clinical Trial. PMID- 27679334 TI - Trainee Participation in Benign Hysterectomy: Effects of Surgical Approach and Operative Time. PMID- 27679335 TI - The Effect of Vertical Versus Horizontal Vaginal Cuff Closure on Vaginal Length After Laparoscopic Hysterectomy. PMID- 27679336 TI - Uterine Retroversion in Rectosigmoid Endometriotic Nodule Affected Women: A New Technique for Uterine Suspension. PMID- 27679338 TI - A Preliminary Report of a Prospective Randomized Controlled Study: Effects of Water-Jet in Laparoscopic Nerve Sparing Radical Hysterectomy for Patients with Cervical Cancer. PMID- 27679337 TI - Impact of the 2014 FDA Warnings Against Laparoscopic Power Morcellation. PMID- 27679339 TI - Cost-Effectiveness of Laparoscopic Hysterectomy With Morcellation Compared to Abdominal Hysterectomy for Presumed Benign Leiomyomata. PMID- 27679340 TI - Feasibility and Outcomes of Laparoscopic Cytoreduction in Patients With Localized Recurrent Epithelial Ovarian Cancer. PMID- 27679341 TI - Obesity and the Likelihood of a Minimally Invasive Procedure Among Surgeons With and Without Advanced Surgical Training. PMID- 27679342 TI - Comparison of Methods of Morcellation: Manual Versus Power. PMID- 27679343 TI - Laparoscopic Versus Robotic Surgery Learning Curves. PMID- 27679344 TI - A Wireless Audio System Improves Teamwork and Communication in Robotic Laparoscopic Surgery. PMID- 27679345 TI - Endoscopy Surgery for Ectopic Pregnancy Within Cesarean Scar. PMID- 27679346 TI - Risk Factors Associated With Emergency Room Visits and Hospital Readmission Following Benign Hysterectomy. PMID- 27679347 TI - Laparoscopic Bowel Resection for Deep Infiltrating Endometriosis: The CARE Experience. PMID- 27679348 TI - Effect of Uterine Manipulation on the Relation of the Ureter and the Uterine Vessels. PMID- 27679349 TI - Feasibility of Washings at the Time of Laparoscopic Power Morcellation: A Pilot Study. PMID- 27679350 TI - Power Morcellation Moratorium and Its Effect on the Rate of Wound Complications After Minimally Invasive Myomectomy (MIM). PMID- 27679351 TI - Risk factors for Trachelectomy Following Supracervical Hysterectomy. PMID- 27679352 TI - Estimating Incidence of Leiomyosarcoma After Minimally Invasive Total Hysterectomy Less Than 250 gram Uteri: Retrospective Cohort Study. PMID- 27679353 TI - Laparoscopic and Robotic Myomectomy: A Comparison of Cost and Perioperative Outcomes for Complex Cases. PMID- 27679354 TI - Placental Remnant Removal With the Hysteroscopic Morcellator. PMID- 27679356 TI - Long-Term Complications and Efficacy After Retropubic Tension-Free Vaginal Tape and Inside-Out Obturator Tape: A Prospective Randomized Trial. PMID- 27679355 TI - Contained Tissue Extraction Using Power Morcellation: Prospective Evaluation of Leakage Parameters. PMID- 27679357 TI - Feasibility of Minimally Invasive Outpatient Hysterectomy. PMID- 27679358 TI - Pre-Laparoscopic Ultrasound "Soft Marker" Evaluation of Ovarian Mobility in the Normal and Endometriotic Ovary. PMID- 27679359 TI - Decrease in Anti-Mullerian Hormone After Laparoscopic Excision of Endometrioma. PMID- 27679360 TI - National Trends of Bilateral Salpingectomy During Vaginal Hysterectomy With and Without Laparoscopic Assistance, United States 1998-2011. PMID- 27679361 TI - In-Bag Transvaginal Specimen Extraction After Laparoscopic Myomectomy: A Single Centre Analysis. PMID- 27679362 TI - Cost of Disposable Operative Devices: Fiscal Transparency Promotes Economic and Ergonomic Optimization at a Large Academic Medical Center. PMID- 27679363 TI - Vaginal Uterine Morcellation Within a Specimen Containment System: A Study of Bag Integrity. PMID- 27679364 TI - Hysterectomy for Uteri Weighing >=1kg: Laparoscopic Vs. Open Approach. PMID- 27679365 TI - Uterine Weight as a Positive Correlation Factor for Longer Surgical Times in Total Laparoscopic Hysterectomy. PMID- 27679366 TI - Effect of Intraoperative Peritoneal Irrigation of Xylocaine on Small and Large Bowel Activity. PMID- 27679367 TI - Laparoscopic Hysterectomies for Uteri Greater Than 1 Kilogram. PMID- 27679368 TI - Urologic Complications After Laparoscopic Radical Hysterectomy and Abdominal Radical Hysterectomy in Patients With Early Cervical Cancer: A Prospective Randomized Study. PMID- 27679369 TI - Implementation of an Office Surgery Safety Checklist. PMID- 27679370 TI - Factors Predicting the Success Rate of a Single Dose of Systemic Methotrexate for the Treatment of Ectopic Pregnancy. PMID- 27679371 TI - A Retrospective Review of the Combination of Unfractionated Heparin and Ketorolac on Bleeding Complications After Obstetric and Gynecologic Surgeries. PMID- 27679372 TI - Computerized Tomography Adiposity Morphometrics: A Novel Approach to Predict Pulmonary Intolerance in Endometrial Cancer Patients Undergoing Robotic Pelvic Surgery (RPS). PMID- 27679373 TI - Factors Associated With Symptomatic Anemia and Indication for Blood Transfusion After Total Laparoscopic Hysterectomies. PMID- 27679374 TI - Public Interest in Morcellation Controversy. PMID- 27679375 TI - Surgeon's Heart Rate Measurements as a Means of Evaluating Proficiency in Newly Adopted Surgical Technique in Gynecologic Oncology Surgery. PMID- 27679376 TI - Single Institutional Experience of 410 Cases of Type B & Type C (Querleu Morrow Classification) Laparoscopic Radical Hysterectomy. PMID- 27679378 TI - Low-Dose Mifepristone Versus Placebo to Treat Uterine Myoma: A Double-Blind, Randomized Clinical Trial. PMID- 27679377 TI - Metabolic Syndrome: Predictive Factor for Endometrial Polyps in Postmenopausal Women. PMID- 27679379 TI - Perioperative Outcomes of Total Laparoscopic Hysterectomy With Uncontained Versus Contained Power Morcellation. PMID- 27679380 TI - Determinants and Trends of Gynecologic Minimally Invasive Surgery in Developing Countries. PMID- 27679381 TI - A Multi-Center Retrospective Review of Clinical Characteristics of Uterine Sarcoma. PMID- 27679382 TI - Multidisciplinary Recommendation for Postoperative Recovery Time following Gynecological Surgery. PMID- 27679383 TI - The Incidence of Occult Malignancy Encountered During Uterine Surgery for Benign Indications. PMID- 27679384 TI - Implementing the Laparoscopic Hysterectomy, Is the Vaginal Approach at Risk? PMID- 27679385 TI - Total Laparoscopic Hysterctomy for Endometriosis: A Single-Center Retrospective Comparative Analysis. PMID- 27679386 TI - Outcomes of Laparoscopic Treatment of Rectosigmoid Endometriosis: The Linear Nodulectomy and the Segmental Ressection. PMID- 27679387 TI - Evaluation of Patient Characteristics Associated With Mode of Hysterectomy and Conversion Rate. PMID- 27679388 TI - Specialty-Specific Operative Units Promote Cost-Effectiveness and Patient Safety. PMID- 27679389 TI - Total Laparoscopic Hysterectomy (TLH): Where Does the Money Go? PMID- 27679390 TI - Fibroid Morcellation: A Shared Clinical Decision Tool for Mode of Hysterectomy. PMID- 27679391 TI - Identifying the Rate-Limiting Step in Total Laparoscopic Hysterectomy in a Training Hospital. PMID- 27679392 TI - Case Selection Is a Fundamental Prerequisite to the Successful Surmounting of Learning Curve of Laparoscopic Radical Hysterectomy in Early-Stage Cervical Cancer: A Matched-Case Comparison in a Single Institution. PMID- 27679393 TI - Successful Adoption of Single-Port Laparoscopy for Gynecologic Indications: Outcomes From a Large Single Institution's Experience. PMID- 27679394 TI - Power Morcellation in Gynecologic Surgery: A Survey of Canadian Practice. PMID- 27679395 TI - 50% Dextrose as the Distension Medium to Improve Visualization of Ureteric Jets During Postoperative Cystoscopy. PMID- 27679396 TI - Longitudinal Course of Fibroid Volume Reduction and Symptom Relief After Transcervical Radiofrequency Ablation. PMID- 27679397 TI - Direct effects of ethanol on neuronal differentiation: An in vitro analysis of viability and morphology. AB - The deleterious effects of ethanol (EtOH) on the brain have been widely described, but its effects on the neuronal cytoskeleton during differentiation have not yet been firmly established. In this context, our aim was to investigate the direct effect of EtOH on cortical neurons during the period of differentiation. Primary cultures of cortical neurons obtained from 1-day-old rats were exposed to EtOH after 7days of culture, and viability and morphology were analyzed at structural and ultrastructural levels after 24-h EtOH exposure. EtOH caused a significant reduction of 73+/-7% in the viability of cultured cortical neurons, by preferentially inducing apoptotic cellular death. This effect was accompanied by an increase in caspase 3 and 9 expression. Furthermore, EtOH induced a reduction in total dendrite length and in the number of dendrites per cell. Ultrastructural studies showed that EtOH increased the number of lipidic vacuoles, lysosomes and multilamellar vesicles and induced a dilated endoplasmatic reticulum lumen and a disorganized Golgi apparatus with a ring shape appearance. Microtubules showed a disorganized distribution. Apposition between pre- and postsynaptic membranes without a defined synaptic cleft and a delay in presynaptic vesicle organization were also observed. Synaptophysin and PSD95 expression, proteins pre- and postsynaptically located, were reduced in EtOH-exposed cultures. Overall, our study shows that EtOH induces neuronal apoptosis and changes in the cytoskeleton and membrane proteins related with the establishment of mature synapses. These direct effects of EtOH on neurons may partially explain its effects on brain development. PMID- 27679398 TI - Protective effects of batroxobin on a nigrostriatal pathway injury in mice. AB - Traumatic brain injury triggers a series of damaged processes, such as neuronal death and apoptosis, inflammation and scar formation, which contribute to evolution of brain injury. The present study investigated the neuroprotective effects of batroxobin, a drug widely used clinically for ischemia, in a nigrostriatal pathway injury model. Mice subjected to the nigrostriatal pathway injury were injected with batroxobin (30 BU/kg) or vehicle immediately after injury. The behavioral studies showed that batroxobin could improve the motor function in injured mice in long term. Batroxobin also reduced neuronal apoptosis and inflammation at the acute stage. Moreover, administration of batroxobin attenuated the scar formation and reduced the lesion size at 4 and 14days after brain injury. These results suggest that batroxobin has beneficial effects on the nigrostriatal pathway injury, indicating a potential clinical application. PMID- 27679399 TI - Influence of volumetric 4'-[methyl-11C]-thiothymidine PET/CT parameters for prediction of the clinical outcome of head and neck cancer patients. AB - OBJECTIVE: This prospective study compared the value of pretreatment 4'-[methyl 11C]-thiothymidine (11C-4DST) volumetric parameters and those of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) in predicting the clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Fifty patients with HNSCC underwent 11C-4DST PET/CT and 18F-FDG PET/CT prior to anticancer therapy. 18F-FDG metabolic tumor volume (18F-FDG MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET, and 11C-4DST MTV and total lesion proliferation (TLP) were calculated from 11C-4DST PET. All parameters were measured for the primary lesion and metastatic lymph nodes. Associations between clinical factors and PET/CT parameters and prognostic value were analyzed. RESULTS: Receiver operating characteristic analysis revealed that MTV, TLG, and TLP acquired from the primary lesion and metastatic lymph nodes were good parameters for predicting disease relapse and death. The area under the curves (AUCs) ranged from 0.63 to 0.71 for 18F-FDG PET/CT parameters. The AUCs of 11C-4DST PET/CT parameters were larger than those of 18F-FDG (range 0.72-0.81). Univariate analysis revealed that individuals with tumors showing a high value for any PET/CT parameter were at a significantly increased risk of relapse. Upon multivariate analysis, 18F-FDG MTV, 11C-4DST MTV and 11C-4DST TLP were significant independent factors for relapse free survival (P = 0.04, P = 0.0001 and P = 0.0005, respectively). CONCLUSION: Pretreatment 11C-4DST PET/CT volume-based parameters can provide important prognostic information about patients with HNSCC. PMID- 27679400 TI - Nonsteroidal anti-inflammatory drug use in patients with chronic kidney disease. AB - AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of pain management. There are no detailed data on NSAIDs use in Poland, especially in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the frequency, circumstances, and causes of NSAIDs use as well as knowledge of their side-effects in patients with CKD. METHOD: This cross-sectional study was conducted in 972 individuals with CKD, enrolled in a written survey originally developed by the authors. There were 574 patients with CKD stage I-IV, 414 patients after renal transplantation stage II-IV (CKDT) and 84 dialyzed patients (44 peritoneal, 40 hemodialysis). RESULTS: Among the entire study group, 16.9 % of patients used NSAIDs every day, or several times a week. The average number of tablets taken within a month was 21.8. Subgroup analysis revealed that NSAIDs were taken most often by patients on hemodialysis: 35 % of them used NSAIDs every day or several times a week (43.15 pills per month). The most common reason for using NSAIDs were bone-joint pain (29.3 %) and headache (26.2 %). Side effects of painkillers such as renal function deterioration and the possible promotion of stomach ulcers were experienced by 43.6 and 37.6 % of respondents, respectively. CONCLUSION: Patients with CKD often take NSAIDs. This applies especially to the group of people undergoing hemodialysis, which is mainly associated with chronic osteo-articular pain. The results also show a low awareness of painkillers' adverse effects. PMID- 27679402 TI - Psychological responses, coping and supporting needs of healthcare professionals as second victims. AB - AIM: To provide an overview of healthcare professionals' psychological responses, coping strategies and supporting needs in the aftermath of an adverse event, thus informing health policy implications and future research in this aspect. BACKGROUND: Trauma experienced by healthcare professionals as second victims potentially provokes intense emotional distress, detrimental professional outcomes and imposes harsh long-term effects. METHODS: A systematic literature review was performed to synthesize the experiences and needs of second victims who are healthcare professionals being traumatized by an unanticipated adverse event, medical error or patient-related injury. CINAHL, Embase, PsycINFO, PubMed and Scopus databases were searched for relevant articles published in English from January 2000 to October 2015. RESULTS: Data extraction was performed for the 30 studies selected. Second victims experienced enduring intense negative psychological responses. They adopted multiple coping mechanisms and desired emotional and informational support. CONCLUSION: Second victims experience substantial psychological impact which can be mitigated with supportive environments. It is imperative that subsequent research consider the potential factors affecting second victims' emotional experience, efficacy of coping strategies in facilitating recovery and obtain a comprehensive understanding of second victims' experience. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nursing and health management's role in establishing organizational support structures is necessary to meet second victims' needs. This existing knowledge is significant to guide policy makers in developing a holistic and effective second victim support programme. PMID- 27679403 TI - Anterior lens epithelium in cataract patients with retinitis pigmentosa - scanning and transmission electron microscopy study. AB - PURPOSE: In retinitis pigmentosa (RP) patients, relatively minor lens opacity in central part of posterior pole of the lens may cause disproportionate functional symptoms requiring cataract operation. To investigate the possible structural reasons for this opacity development, we studied the structure of the lens epithelium of patients with RP. METHODS: The anterior lens capsule (aLC: basement membrane and associated lens epithelial cells, LECs) was obtained from cataract surgery and prepared for scanning and transmission electron microscopy (SEM and TEM). RESULTS: Both SEM and TEM show a number of abnormal features in the anterior lens epithelium of cataract patients with RP. The abnormalities appear mainly as holes, thinning and degradation of the epithelium, with the dimensions from <1 MUm to more than 50 MUm. Other types of holes in size up to 20 MUm were seen that may be formed by gradual stretching of the lens epithelium. Another type of abnormalities was cracks that were seen between adjacent LECs, with dimensions 0.1-2 MUm * up to 10 MUm. CONCLUSIONS: Abnormal structural features were observed in the anterior lens epithelium that may cause water influx into the lens. This may lead to clouding along the water clefts leading towards the posterior pole in the RP cataractous lens. We suggest that the lens epithelium has a role in the development of the cataract in patients with RP. PMID- 27679401 TI - Renoprotective effect of erythropoietin in zebrafish after administration of gentamicin: an immunohistochemical study for beta-catenin and c-kit expression. AB - BACKGROUND: Gentamicin is an aminoglycoside antibiotic widely used in the treatment of infections caused by Gram-negative bacteria. The main limitation to its therapeutic effectiveness is the potential nephrotoxicity. Erythropoietin has a tissue protective effect widely demonstrated in the kidney. The aim of the present study was to evaluate the renoprotective effects of erythropoietin in a model of zebrafish (Danio rerio) after administration of gentamicin. METHODS: Sixty adult zebrafish were subdivided into three groups: group A was treated with gentamicin; group B received gentamicin and, 24 h later, epoetin alpha; group C received drug diluent only. In order to analyze the renoprotective activity of erythropoietin, the expression of c-kit and beta-catenin was evaluated by immunohistochemistry. RESULTS: Generally, the zebrafish renal tubule regenerates 15 days after an injury. Conversely, 7 days after gentamicin administration, animals treated with erythropoietin (group B) showed a better renal injury repair as documented by: increased expression of beta-catenin, less degenerated tubules, greater number of centers of regeneration, positivity for c-kit only in immature looking tubules and lymphohematopoietic cells. CONCLUSION: The expression of c kit and beta-catenin suggests that erythropoietin may exert a role in regeneration reducing the extent of tubular damage from the outset after gentamicin administration. PMID- 27679404 TI - A study of the efficacy of platelet-rich plasma in the treatment of androgenetic alopecia in males. PMID- 27679405 TI - Warty mucosal lesions: Oral condyloma lata of secondary syphilis. PMID- 27679406 TI - Cutaneous toxicity of a new BRAF inhibitor, LGX818 (encorafenib). PMID- 27679407 TI - Sub-block level monitoring in leprosy programme: Need of the hour. PMID- 27679408 TI - Neurological diseases and bullous pemphigoid: A case-control study in Iranian patients. AB - INTRODUCTION: Neurological diseases are important co-morbidities found in association with bullous pemphigoid. Various neurological conditions (stroke, Parkinson's disease, dementia, epilepsy and multiple sclerosis) have been reported as associations of this bullous disease; whether these are significant has not been definitely proved. However, the presence of neurological conditions is a predictor of poorer prognosis. OBJECTIVES: Our aim was to examine the association of bullous pemphigoid and neurological diseases in Iranian bullous pemphigoid patients. METHODS: The medical records of one hundred and sixty consecutive bullous pemphigoid patients who presented to the Autoimmune Bullous Diseases Research Center, Tehran, Iran, from 2006 to 2011 were examined for evidence of any neurological disease. The control group comprised of 317 age- and sex-matched subjects. RESULTS: Neurological diseases were seen in 42 (26.4%) patients with bullous pemphigoid and in 29 (9.1%) controls (odds ratio: 3.53 (2.1 5.9), P< 0.001). Comparing cases to controls, stroke was seen in 17.5% versus 4.1%, odds ratio 4.96 (2.49-9.88); dementia in 5.6% versus 1.9%, odds ratio 3.09 (1.08-8.84); Parkinson's disease in 2.5% versus 2.2%, odds ratio 1.14 (0.33 3.94); epilepsy in 2.5% versus 0.6%, odds ratio 4.04 (0.73-22.3); and multiple sclerosis in 0 versus 0.3% odds ratio 1.00 (0.98-1.01). LIMITATIONS: The main limitations of our study were referral bias, retrospective design and a rather low sample size. CONCLUSIONS: Neurological diseases in general, and stroke and dementia in particular, were significantly associated with bullous pemphigoid in our study. PMID- 27679409 TI - Uncombable hair syndrome with a woolly hair nevus. PMID- 27679411 TI - Utility of high-frequency ultrasonography in the diagnosis of benign and malignant skin tumors. AB - Various benign and malignant tumors may arise from the skin. These may be of epidermal, dermal, subcutaneous or appendageal origin. Skin biopsy is the gold standard for diagnosis of skin tumors. There is paucity of published data on the role of imaging modalities in diagnosis of skin tumors. High-frequency ultrasonography (7-50 MHz) is a potential non-invasive, objective modality which can be utilized in the diagnosis and localization of skin tumors. It provides valuable information about the tumor characteristics such as size, shape, depth, consistency and vascularity before invasive skin biopsy or surgery is planned. Sentinel lymph nodes in malignant melanoma can be well visualized and studied by this technique. It is also a good modality to detect local recurrence of tumors during post-operative follow up, especially those with a high likelihood of local recurrence or lesions excised with inadequate margins. High-frequency ultrasonography is additive to clinical diagnosis and can be considered a useful non-invasive method to plan the management of various skin tumors and is of prognostic value in some cases. PMID- 27679412 TI - Histamine Clearance Through Polyspecific Transporters in the Brain. AB - Histamine plays an important role as a neurotransmitter in diverse brain functions, and clearance of histamine is essential to avoid excessive histaminergic neuronal activity. Histamine N-methyltransferase, which is an enzyme in the central nervous system that metabolizes histamine, is localized to the cytosol. This suggests that a histamine transport process is essential to inactivate histamine. Previous reports have shown the importance of astrocytes for histamine transport, although neuronal histamine transport could not be ruled out. High-affinity and selective histamine transporters have not yet been discovered, although it has been reported that the following three polyspecific transporters transport histamine: organic cation transporter (OCT) 2, OCT3, and plasma membrane monoamine transporter (PMAT). The K m values of human OCT2, OCT3, and PMAT are 0.54, 0.64, and 4.4 mM, respectively. The three transporters are expressed in the brain, and their regional distribution is different. Recent studies revealed the contribution of OCT3 and PMAT to histamine transport by primary human astrocytes. Several investigations using mice supported the importance of OCT3 for histamine clearance in the brain. However, further studies are required to elucidate the detailed mechanism of histamine transport in the brain. PMID- 27679413 TI - What are the Considerations in Balancing Benefits and Risks in Iron Treatment?: The Benefits of Intravenous Iron. PMID- 27679414 TI - Virus Discovery Using Tick Cell Lines. AB - While ticks have been known to harbor and transmit pathogenic arboviruses for over 80 years, the application of high-throughput sequencing technologies has revealed that ticks also appear to harbor a diverse range of endogenous tick-only viruses belonging to many different families. Almost nothing is known about these viruses; indeed, it is unclear in most cases whether the identified viral sequences are derived from actual replication-competent viruses or from endogenous virus elements incorporated into the ticks' genomes. Tick cell lines play an important role in virus discovery and isolation through the identification of novel viruses chronically infecting such cell lines and by acting as host cells to aid in determining whether or not an entire replication competent, infective virus is present in a sample. Here, we review recent progress in tick-borne virus discovery and comment on the actual and potential applications for tick cell lines in this emerging research area. PMID- 27679415 TI - Proliferation and apoptosis processes in the seasonal testicular development of the wild Daurian ground squirrel (Citellus dauricus Brandt, 1844). AB - The aim of the present study was to elucidate the regulatory role of cell proliferation and apoptosis in testicular development of wild Daurian ground squirrels during the breeding season (April), the non-breeding season (June) and before hibernation (September). Gross mass and hormonal analysis showed that the testis:body mass ratio and plasma testosterone concentration fluctuated seasonally, with a peak in April and lowest values in June. Similarly, spermatogenesis was fully developed in April but suppressed in June and September. Testicular decellularisation and vacuolisation was seen during the transition from the breeding to the non-breeding season. Furthermore, testicular levels of proliferating cell nuclear antigen, cyclin D2 and caspase-3 protein were significantly increased in June and September. Intriguingly, positive terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labelling staining and nuclear translocation of caspase-3 in testicular germ cells appeared only during the prehibernation period, whereas accumulation of cyclin D2 in spermatocyte nuclei occurred in September. These findings demonstrate, for the first time, that both cell proliferation and apoptosis are stimulated during the prehibernation period, indicating that a hormonal-regulated balance of testicular germ cell proliferation and apoptosis may play a pivotal role in preparing for testicular recrudescence of wild Daurian ground squirrels. PMID- 27679417 TI - Retrieval of embolized left atrial appendage devices. AB - Percutaneous left atrial appendage (LAA) closure is gaining interest as an alternative option for prevention of strokes in patients with Atrial Fibrillation (AF), especially for those with contraindications to anticoagulation. Complications from these procedures are well described in the medical literature. LAA closures may lead to pericardial effusion, device-associated thrombus, and device embolization. Understanding the reasons for embolization, strategies to avoid embolization, and the techniques for retrieval of LAA devices (ACP/AMULET and WATCHMAN) should be appreciated by endovascular implanters. We describe two cases of LAA device embolization that were both successfully retrieved percutaneously and other percutaneous techniques to safely retrieve embolized LAA devices. (c) 2016 Wiley Periodicals, Inc. PMID- 27679416 TI - Increased neutrophil expression of pattern recognition receptors during COPD exacerbations. AB - Previously, we observed increased serum levels of damage-associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of toll-like receptor (TLR)2, TLR4 and NLR family, pyrin domain-containing 3 (NLRP3) was significantly increased, while serum levels of the soluble form of the decoy receptor for advanced glycation end-product (sRAGE) were decreased during exacerbation. Together, these data indicate that increased DAMP signalling contributes to activation of neutrophils during COPD exacerbations. PMID- 27679420 TI - Growing up on a farm may cut risk of allergic conditions in adulthood. PMID- 27679418 TI - Effect of alcohol consumption on all-cause and liver-related mortality among HIV infected individuals. AB - OBJECTIVES: The aim of the study was to examine the association between levels of past and current alcohol consumption and all-cause and liver-related mortality among people living with HIV (PLWH). METHODS: A prospective cohort study of 1855 PLWH in Baltimore, MD was carried out from 2000 to 2013. We ascertained alcohol use by (1) self-report (SR) through a computer-assisted self interview, and (2) medical record abstraction of provider-documented (PD) alcohol use. SR alcohol consumption was categorized as heavy (men: > 4 drinks/day or > 14 drinks/week; women: > 3 drinks/day or > 7 drinks/week), moderate (any alcohol consumption less than heavy), and none. We calculated the cumulative incidence of liver-related mortality and fitted adjusted cause-specific regression models to account for competing risks. RESULTS: All-cause and liver-related mortality rates (MRs) were 43.0 and 7.2 per 1000 person-years (PY), respectively. All-cause mortality was highest among SR nondrinkers with PD recent (< 6 months) heavy drinking (MR = 85.4 deaths/1000 PY) and lowest among SR moderate drinkers with no PD history of heavy drinking (MR = 23.0 deaths/1000 PY). Compared with SR moderate drinkers with no PD history of heavy drinking, SR nondrinkers and moderate drinkers with PD recent heavy drinking had higher liver-related mortality [hazard ratio (HR) = 7.28 and 3.52, respectively]. However, SR nondrinkers and moderate drinkers with a PD drinking history of > 6 months ago showed similar rates of liver-related mortality (HR = 1.06 and 2.00, respectively). CONCLUSIONS: Any heavy alcohol consumption was associated with all-cause mortality among HIV-infected individuals, while only recent heavy consumption was associated with liver related mortality. Because mortality risk among nondrinkers varies substantially by drinking history, current consumption alone is insufficient to assess risk. PMID- 27679419 TI - Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. AB - Glycosylation is one of the major posttranslational modifications of proteins. N glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment. The unique molecular chaperone of T synthase is Cosmc, which helps T-synthase to fold correctly in the endoplasmic reticulum. Dysregulation of these glycosyltransferases, molecular chaperones, or the environment is involved in the dysregulation of O-glycans. Tn, sTn, and T antigen neo- or over-expression occurs in many types of cancer including gastric, colon, breast, lung, esophageal, prostate, and endometrial cancer. This review discusses the major synthetic pathway of O-glycans and the mechanism by which Tn, sTn, and T antigens promote tumor metastasis. PMID- 27679421 TI - Septectomy and biatrial resection for extensive septal lipomatosis. AB - We describe the resection for lipomatous hypertrophy of the interatrial septum which necessitated complete reconstruction of the right atrium with Dacron grafts connecting the superior and inferior vena cava with the tricuspid orifice, and connection of the pulmonary veins to the mitral orifice with xenopericardium. PMID- 27679422 TI - The variability in beta-cell function in placebo-treated subjects with type 2 diabetes: application of the weight-HbA1c-insulin-glucose (WHIG) model. AB - AIM: The weight-glycosylated haemoglobin (HbA1C)-insulin-glucose (WHIG) model describes the effects of changes in weight on insulin sensitivity (IS) in newly diagnosed, obese subjects receiving placebo treatment. This model was applied to a wider population of placebo-treated subjects, to investigate factors influencing the variability in IS and beta-cell function. METHODS: The WHIG model was applied to the WHIG dataset (Study 1) and two other placebo datasets (Studies 2 and 3). Studies 2 and 3 consisted of nonobese subjects and subjects with advanced type 2 diabetes mellitus (T2DM). Body weight, fasting serum insulin (FSI), fasting plasma glucose (FPG) and HbA1c were used for nonlinear mixed effects modelling (using NONMEM v7.2 software). Sources of interstudy variability (ISV) and potential covariates (age, gender, diabetes duration, ethnicity, compliance) were investigated. RESULTS: An ISV for baseline parameters (body weight and beta-cell function) was required. The baseline beta-cell function was significantly lower in subjects with advanced T2DM (median difference: Study 2: 15.6%, P < 0.001; Study 3: 22.7%, P < 0.001) than in subjects with newly diagnosed T2DM (Study 1). A reduction in the estimated insulin secretory response in subjects with advanced T2DM was observed but diabetes duration was not a significant covariate. CONCLUSION: The WHIG model can be used to describe the changes in weight, IS and beta-cell function in the diabetic population. IS remained relatively stable between subjects but a large ISV in beta-cell function was observed. There was a trend towards decreasing beta-cell responsiveness with diabetes duration, and further studies, incorporating subjects with a longer history of diabetes, are required. PMID- 27679423 TI - Hypoxia and low-dose inflammatory stimulus synergistically enhance bone marrow mesenchymal stem cell migration. AB - OBJECTIVES: Cell migration is necessary for numerous physiological cell processes. Although either inflammatory or hypoxic stimuli of certain dose and duration have positive influence on cell migration, their combination has not been shown to result in a synergistic effect. MATERIALS AND METHODS: In this study, we investigated combined effects of hypoxia and low-dose inflammatory stimulus (one-tenth of that of a previously used concentration) on migration of human bone marrow-derived mesenchymal stem cells (BMMSCs). RESULTS: Our results from real-time PCR, Western blot analysis and an immunofluorescence assay, showed that dual stimulation up-regulated CXCR4 expression. Based on tablet scratch experimentation and transwell assay, the dual stimuli exhibited greater positive effects on cell migration than a single inflammatory or hypoxic stimulus. When effects of various pre-treatments on cell proliferation, differentiation and immunosuppression were screened, cells subjected to the hypoxic stimulus or dual stimuli had increased cell proliferation, while short-term inflammatory stimulus and/or hypoxic stimulus had no negative effect on cell differentiation and immunosuppression. CONCLUSIONS: These findings suggest that the combination of hypoxia and low-dose inflammatory stimuli enhances the potential of BMMSCs to migrate, thus identifying cell pre-treatment conditions that could enhance future stem cell-based therapeutics. PMID- 27679424 TI - Fatal hemolytic disease of the newborn caused by an antibody to KEAL, a new low prevalence Kell blood group antigen. PMID- 27679425 TI - DNA-Nanostructure-Gold-Nanorod Hybrids for Enhanced In Vivo Optoacoustic Imaging and Photothermal Therapy. AB - A functional cancer theranostic nanoplatform is developed, specifically tailored toward the optoacoustic modality by combining gold nanorods with DNA nanostructures (D-AuNR). DNA origami is used as an efficient delivery vehicle owing to its prominent tumor-targeting property. The D-AuNR hybrids display an enhanced tumor diagnostic sensitivity by improved optoacoustic imaging and excellent photothermal therapeutic properties in vivo. PMID- 27679426 TI - Is the canine corpus luteum an insulin-sensitive tissue? AB - This study aimed to determine in the canine corpus luteum throughout the dioestrus (1) the influence of insulin on glucose uptake; (2) the regulation of genes potentially involved; and (3) the influence of hypoxia on glucose transporter expression and steroidogenesis, after treatment with cobalt chloride (CoCl2). Glucose uptake by luteal cells increased 2.7 folds (P < 0.05) in response to insulin; a phenomenon related to increased expression of glucose transporter (GLUT) 4 and phosphorylation of protein kinase B (AKT). The gene expression of insulin receptor and SLC2A4 (codifier of GLUT4) genes after insulin stimulation increased on day 20 post ovulation (p.o.) and declined on day 40 p.o. (P < 0.05). Regarding potentially involved molecular mechanisms, the nuclear factor kappa B gene RELA was upregulated on days 30/40 p.o., when SLC2A4 mRNA was low, and the interleukin 6 (IL6) gene was upregulated in the first half of dioestrus, when SLC2A4 mRNA was high. CoCl2 in luteal cell cultures increased the hypoxia-inducible factor HIF1A/HIF1A and the SLC2A4/GLUT4 expression, and decreased progesterone (P4) production and hydroxyl-delta-5-steroid dehydrogenase 3 beta (HSD3B) mRNA expression (P < 0.05). This study shows that the canine luteal cells are responsive to insulin, which stimulates glucose uptake in AKT/GLUT4-mediated pathway; that may be related to local activity of RELA and IL6. Besides, the study reveals that luteal cells under hypoxia activate HIF1A modulating luteal function and insulin-stimulated glucose uptake. These data indicate that insulin regulates luteal cells' glucose disposal, participating in the maintenance and functionality of the corpus luteum. PMID- 27679427 TI - D-Shuttle project: measurement and comparison of individual doses of high school students. AB - In 2014, a team of high school students and teachers measured individual exposure doses using D-Shuttle dosimeters. In total, 216 students and teachers participated in the project, with the cooperation of 12 high schools in Japan (six from Fukushima Prefecture), four from France, eight from Poland, and two from Belarus. The participants wore the dosimeters for 2 weeks and recorded their locations in diary charts. The distribution of annual exposure doses for each school and region, estimated from the measured results, overlapped. It was concluded that the external exposure of high school students in Fukushima Prefecture was not markedly higher compared with that of students from other regions. PMID- 27679428 TI - Single-centre experience of the macrophage activation marker soluble (s)CD163 - associations with disease activity and treatment response in patients with autoimmune hepatitis. AB - BACKGROUND: Autoimmune hepatitis (AIH) is characterised by liver inflammation with reversibility upon anti-inflammatory treatment. Soluble (s)CD163, a specific macrophage activation marker, is associated with inflammation in other liver diseases, but never investigated in AIH. AIM: To investigate sCD163 in patients with acute AIH and in complete and incomplete responders to standard anti inflammatory pharmacotherapy, and during follow-up in treatment naive patients. METHODS: In a cross-sectional design, we studied 121 AIH patients (female/male 89/32, median age 49 years); of these, we prospectively studied 10 treatment naive AIH patients during prednisolone treatment and tapering. Twenty patients had variant syndromes of AIH and primary biliary cholangitis or primary sclerosing cholangitis. sCD163 was compared with markers of disease activity, severity and treatment response. RESULTS: In the patients with acute AIH (n = 21), sCD163 was sixfold increased compared with the normalised levels in patients (n = 32) with complete response to standard treatment [9.5 (3.3-28.8) vs. 1.6 (0.8-3.2) mg/L, P < 0.01)], while the patients (n = 27) with incomplete response had higher sCD163 [2.2 (1.3-7.9), P < 0.05] than the complete responders. sCD163 was positively associated with ALAT, IgG and bilirubin (rho: 0.45-0.59, P < 0.001, all), and negatively to external coagulation factors (rho:-0.34, P < 0.001). In the treatment naive patients, sCD163 fell during high-dose prednisolone treatment and tapering. Immunohistochemical staining confirmed increased CD163 expression in liver biopsies from patients with acute AIH. CONCLUSIONS: sCD163 was markedly elevated in AIH in the acute phase, normalised by successful treatment in complete responders, but remained higher in the incompletely responding cases. Our results demonstrate macrophage activation in AIH paralleling disease activity, severity and treatment response, suggesting a role for macrophage activation in AIH. PMID- 27679429 TI - Psychological Impact of Severe Obesity. AB - The causes of severe obesity are multifactorial and include metabolic, dietary, physical, and psychological aspects. Additionally, the impact of severe obesity affects more than one's physical health. This article attempts to explore the psychological impact of severe obesity specifically in the areas of mood, eating disorders, sleep disturbance, chronic pain, and quality of life. Additionally, obesity treatment options of lifestyle modification and bariatric surgery that include psychological assessment and/or cognitive behavioral intervention are discussed. PMID- 27679430 TI - Selecting caudal fusion levels: 2 year functional and stiffness outcomes with matched pairs analysis in multilevel fusion to L5 versus S1. AB - PURPOSE: Controversy persists as to whether to end multilevel thoracolumbar fusions caudally at L5 or S1. Some argue that stopping at L5 may preserve greater function, but there are few data comparing functional limitations due to lumbar stiffness in patients with fusion to L5 versus S1. The aim of this study was to evaluate whether patients undergoing multilevel thoracolumbar fusions with an L5 caudal endpoint have a better lumbosacral function than patients with an S1 caudal endpoint. METHODS: Patients undergoing successful thoracolumbar fusion of 5 or more levels to L5 or S1, with solid fusion at 2 year follow-up, were examined from a single European center in addition to a multi-center North American database of 237 patients. In total, 40 patients with a distal stopping point of L5 were matched with a subset of 40 patients with a distal endpoint of S1 +/- pelvic fixation. The L5 and S1 groups were matched for the final Oswestry Disability Index (ODI), Sagittal Vertical Axis (SVA C7-S1), number of fusion levels, and age. Impacts of lumbar stiffness on function as measured by the Lumbar Stiffness Disability Index (LSDI) were compared using the conditional logistic regression. RESULTS: After matching, there was no significant difference between the S1 and L5 groups for the final ODI (29.22 +/- 21.6 for S1 versus 29.21 +/- 21.7 for L5; p = 0.98), SVA (29.5 +/- 40.3 mm for S1 versus 33.7 +/- 37.1 mm for L5; p = 0.97), mean age (61.6 +/- 11.0 years for S1 versus 58.3 +/- 12.6 years for L5; p = 0.23), and number of fusion levels (9.7 +/- 3.3 levels for S1 versus 9.0 +/- 3 levels for L5; p = 0.34). The final 2-year postoperative LSDI scores were not significantly different between the S1 group (28.08 +/- 21.47) and L5 group (29.21 +/- 21.66) (hazard ratio 0.99, 95 % CI 0.97-1.03, p = 0.81). CONCLUSION: The analysis of patients with multilevel thoracolumbar fusions demonstrated that after minimum 2 year follow-up, self-reported functional impacts of lumbar stiffness were not significantly different between the patients with distal endpoints of L5 versus S1. The choice of distal fusion level of L5 does not appear to retain sufficient spinal flexibility to substantially affect postoperative function. LEVEL OF EVIDENCE: Level III. PMID- 27679431 TI - Treating multi-level cervical disc disease with hybrid surgery compared to anterior cervical discectomy and fusion: a systematic review and meta-analysis. AB - PURPOSE: The traditional surgical approach to treat multi-level cervical disc disease (mCDD) has been anterior cervical discectomy and fusion (ACDF). There has been recent development of other surgical approaches to further improve clinical outcomes. Collectively, when elements of these different approaches are combined in surgery, it is known as hybrid surgery (HS) which remains a novel treatment option. A systematic review and meta-analysis was conducted to compare the outcomes of HS versus ACDF for the treatment of mCDD. METHODS: Relevant articles were identified from six electronic databases from their inception to January 2016. RESULTS: From 8 relevant studies identified, 169 patients undergoing HS were compared with 193 ACDF procedures. Operative time was greater after HS by 42 min (p < 0.00001), with less intraoperative blood loss by 26 mL (p < 0.00001) and shorter return to work by 32 days (p < 0.00001). In terms of clinical outcomes, HS was associated with greater C2-C7 range of motion (ROM) preservation (p < 0.00001) and less functional impairment (p = 0.008) after surgery compared to ACDF. There was no significant difference between HS and ACDF with respect to postoperative pain (p = 0.12). The postoperative course following HS was not significantly different to ACDF in terms of length of stay (p = 0.24) and postoperative complication rates (p = 0.18). CONCLUSIONS: HS is a novel surgical approach to treat mCDD, associated with a greater operative time, less intraoperative blood loss and comparable if not superior clinical outcomes compared to ACDF. While it remains a viable consideration, there is a lack of robust clinical evidence in the literature. Future large prospective registries and randomised trials are warranted to validate the findings of this study. PMID- 27679432 TI - Malignant peripheral nerve sheath tumor in the paraspinal region mimicking a benign peripheral nerve sheath tumor: a case report. AB - PURPOSE: Malignant peripheral nerve sheath tumors are extremely rare in the general population and display a predilection for metastasis to the lungs. Here, we present a rare case of a malignant peripheral nerve sheath tumor located in the paraspinal region and highlight the importance of preoperative biopsy in diagnosis of spinal epidural peripheral nerve sheath tumors. METHODS: We describe the clinical course of the patient as well as the radiological and pathological findings of the tumor. RESULTS: A 14-year-old girl presented with a six-month history of sacral pain. Occasionally she experienced left leg pain and abnormal gait. General physical examination revealed sensorial loss in the L5-S1 regions. T1-weighted sagittal MRI showed a hypointense oval mass and the contrast-enhanced T1-weighted axial MRI image showed heterogeneous enhancement of the tumor. On CT imaging, this tumor characteristically appears as a dumbbell-like mass with punctate calcification and widening L5-S1 intervertebral foramen. Complete resection was performed using an anterior approach. Intraoperative pathological examination revealed evidence of malignancy and subsequent immunohistochemical analysis of the tumor confirmed the diagnosis of MPNST. The postoperative course was uneventful and the patient has had significant improvement in her symptoms 1 month postoperatively. CONCLUSIONS: Preoperative biopsy should be routinely performed for pathological differential diagnosis of spinal epidural PNSTs as well as surgical decision-making. Furthermore a combination of clinical manifestation, radiological findings and biopsy should also be pursued for diagnosing these tumors. PMID- 27679433 TI - Impact of Mean Cell Hemoglobin on Hb A1c-Defined Glycemia Status. AB - BACKGROUND: Several hematological alterations are associated with altered hemoglobin A1c (Hb A1c). However, there have been no reports of their influence on the rates of exceeding standard Hb A1c thresholds by patients for whom Hb A1c determination is requested in clinical practice. METHODS: The initial data set included the first profiles (complete blood counts, Hb A1c, fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. RESULTS: Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A1c. Fasting glucose, MCH, and age emerged as predictors of Hb A1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (<=27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A1c, a 1 pg increase in MCH reduced the odds of Hb A1c defined dysglycemia, diabetes and poor glycemia control by 10%-14%. CONCLUSIONS: For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A1c-based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A1c levels in clinical practice. PMID- 27679434 TI - Generation of Full-Length Class I Human Leukocyte Antigen Gene Consensus Sequences for Novel Allele Characterization. AB - BACKGROUND: Routine, high-resolution human leukocyte antigen (HLA) genotyping by next generation sequencing within clinical immunogenetics laboratories can now provide the full-length gene sequence characterization of fully phased HLA alleles. This powerful technique provides insights into HLA variation beyond the traditionally characterized antigen recognition domain, providing sequence annotation across the entire gene including untranslated and intronic regions and may be used to characterize novel alleles from massively parallel sequencing runs. METHODS: We evaluated the utility of the Omixon Holotype HLA assay to generate credible, fully phased full-length gene consensus sequences for 50 individuals at major histocompatibility complex, class I, A (HLA-A), HLA-B, and HLA-C loci (300 genotyped alleles in total) to identify and characterize novel class I HLA alleles using our downstream analytical pipeline. RESULTS: Our analysis revealed that 7.7% (23/300) of genotyped class I HLA alleles contain novel polymorphisms. Interestingly, all of the novel alleles identified by our analysis were found to harbor sequence variations within intronic regions of the respective locus. In total our analysis identified 17 unique novel class I HLA alleles from 23 of the 300 genotyped alleles and generated full-length gene sequence annotations for 9 previously incompletely annotated HLA class I allele sequences derived from 14 of the 300 genotyped alleles. CONCLUSIONS: The demonstrated utility of the Omixon Holotype HLA assay in combination with our downstream analytical framework to generate fully phased, full-length gene consensus sequences for the identification and characterization of novel HLA alleles, facilitates the study of HLA polymorphism beyond the antigen recognition domain in human health and disease. PMID- 27679436 TI - The Use of Targeted Therapies for Precision Medicine in Oncology. PMID- 27679435 TI - Biological Variation of Hemostasis Variables in Thrombosis and Bleeding: Consequences for Performance Specifications. AB - BACKGROUND: Levels of hemostasis factors vary between and within individuals as a result of genetic and environmental factors and analytical variation of the assays. The current state of the art for defining analytical precision requirements for analytical testing is based on this between- and within individual (biological) variation. However, information on biological variation in hemostasis variables is still limited.The aim of this study was to determine the biological variation of coagulation variables involved in thrombosis and bleeding to provide a recommendation for performance specifications and to assess whether hemostasis assays fulfill the recommendation. METHODS: We performed a longitudinal study by repeated blood sampling (in total 13 times over a 1-year period) in 40 healthy individuals and measured prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, factor VIII, factor IX, von Willebrand factor (VWF), protein C, and protein S. We evaluated the effect of the biological variation on parameters of analytical variation and propose required performance specifications. RESULTS: Biological variation was highly different for various hemostasis variables: the within-subject variation ranged from 2.6% (PT) to 25.6% [VWF collagen binding (CB) activity], the between subject variation varied from 4.1% (PT) to 31.2% (VWF:ristocetin cofactor acitivity), and the assay variation from 1.3% (PT) to 12.9% (VWF:CB). CONCLUSIONS: With the reagents and analyzers used in this study, most of the hemostasis tests variables fulfill the current quality criteria for diagnosis and monitoring of routine hemostasis assays. PMID- 27679437 TI - In Silico and Wet Lab Studies Reveal the Cholesterol Lowering Efficacy of Lauric Acid, a Medium Chain Fat of Coconut Oil. AB - The coconut oil (CO) contains 91 % of saturated fatty acids in which 72 % are medium chain fatty acids (MCFAs) like lauric, capric and caprylic acids. In contrast to animal fat, coconut oil has no cholesterol. Despite this fact, CO is sidelined among other vegetable oils due to the health hazards attributed to the saturated fatty acids. Though various medicinal effects of CO have been reported including the hypolipidemic activity, people are still confused in the consumption of this natural oil. In silico analyses and wet lab experiments have been carried out to identify the hypolipidemic properties of MCFAs and phenolic acids in CO by using different protein targets involved in cholesterol synthesis. The molecular docking studies were carried out using CDOCKER protocol in Accelery's Discovery Studio, by taking different proteins like HMG- CoA reductase and cholesterol esterase as targets and the different phytocompounds in coconut as ligands. Molecular docking highlighted the potential of lauric acid in inhibiting the protein targets involved in hyperlipidemics. Further, validation of in silico results was carried out through in vivo studies. The activity of key enzymes HMG- CoA reductase and lipoprotein lipase were found reduced in animals fed with lauric acid and CO. PMID- 27679438 TI - Quality and Antioxidant Activity of Buckwheat-Based Cookies Designed for a Raw Food Vegan Diet as Affected by Moderate Drying Temperature. AB - Buckwheat cookies with various ingredients for raw food vegan diet are usually prepared by soaking them in water at ambient temperature followed by drying at moderate temperature. The aim of this study was to examine the temperature effect on the microbiological quality, antioxidant properties and oxidative stability of lipids of final dried samples. The mixture of ingredients was soaked for 20 h in distilled water, and then cookies were formed and dried in air-forced oven at constant temperature in the range from 40 to 60 degrees C. Total viable counts, fungi, yeasts, coliform and aerobic spore-forming bacteria counts were evaluated in dried samples and were found to decrease during drying at 50 and 60 degrees C. Antioxidant activity was determined by DPPH and ABTS assays, and the former showed the highest value at 40 degrees C. Superoxide dismutase activity was also higher at 40 degrees C in comparison with that at 60 degrees C. The percentage of lipid peroxidation inhibition increased with the increase in drying temperature until 4th day of incubation. While peroxide value was significantly higher in samples dried at 40 degrees C, TBARS values did not show significant changes during the drying process. The results of this study suggest that drying buckwheat-based cookies at 40 degrees C retained their good antioxidant properties but represent a potentially serious microbial hazard. PMID- 27679439 TI - Fructans from Agave tequilana with a Lower Degree of Polymerization Prevent Weight Gain, Hyperglycemia and Liver Steatosis in High-Fat Diet-Induced Obese Mice. AB - Fructans from agave have received specific attention because of their highly branched fructan content. We have previously reported that the degree of polymerization (dp) influences their biological activity. Therefore, the aim of this study was to investigate the effect of unfractionated and fractionated fructans (higher and lower dps) from Agave tequilana in high-fat diet-induced (HFD) obese mice. Fructans with a lower dp (HFD+ScF) decreased weight gain by 30 %, body fat mass by 51 %, hyperglycemia by 25 % and liver steatosis by 40 %. Interestingly, unfractionated fructans (HFD+F) decreased glucose and triglycerides (TG), whereas fractionated fructans with a higher dp (HFD+LcF) decreased TG but not glucose; in contrast, HFD+ScF decreased glucose but not TG. Our findings suggest that both higher and lower dp agave fructans have complementary effects in metabolic disorders related to obesity. These findings may contribute to the development of improved food supplements with a specific ratio combination of fructans with different dps. PMID- 27679441 TI - Zinc, lead, and cadmium levels in serum and milk of lactating women in Ibadan, Nigeria. AB - Zinc (Zn) is known to interact with lead (Pb) and cadmium (Cd) reversing their toxicity and reducing their concentrations. However, lactating women are at high risk of developing Zn deficiency, which may result in Pb and Cd intoxication or increased exposure of breast-fed infants to Pb and Cd from breast milk. The aim of this study was to determine Zn, Pb, and Cd concentrations and examine their relationship in serum and breast milk of lactating women in Ibadan, Nigeria. Ninety-two lactating women were recruited into this study. Anthropometric measurements were assessed by standard methods while serum and breast milk concentrations of Zn, Pb, and Cd were assessed by atomic absorption spectrophotometry. Data analyzed statistically by Student's t test, Pearson's correlation coefficient, and a multiple regression model were significant at p < 0.05. Zn deficiency was observed in 12 (17.1%) of lactating women. Breast milk levels of Zn, Pb, and Cd were significantly higher than their levels in serum, whereas the ratios Zn:Pb and Zn:Cd in milk were significantly less than serum ratios. Significant negative correlation was observed between milk Pb and serum Zn:Pb while milk Cd correlated positively with milk Zn. Significant positive correlations were observed between serum Zn and serum Zn:Pb, serum Zn and serum Zn:Cd, as well as serum Zn:Cd and serum Zn:Pb. Serum Cd and serum Zn were significantly negatively related. Significant negative correlations between serum Pb and serum Zn:Pb as well as milk Zn:Pb. Serum Cd and serum Zn:Pb as well as serum Zn:Cd correlated negatively. Milk Cd and Zn/Cd positively related with milk Pb while milk Zn was a negatively related with milk Pb in a multiple regression model ( R2 = 0.333; p = 0.023). Breast milk may be contaminated by toxic metals. However, Zn supplementation in deficient mothers may protect maternal and infant health. PMID- 27679440 TI - Antioxidant and Anticancer Activities of Walnut (Juglans regia L.) Protein Hydrolysates Using Different Proteases. AB - Walnut (Juglans regia L.) contains approximately 20-25 % protein with abundant essential amino acids. The enzymatic hydrolysate of Persian walnut (Chandler) seed proteins was prepared by incubation with three different proteases, including pancreatic chymotrypsin and trypsin, and a microbial enzyme proteinase K. The hydrolysates were found to possess excellent antioxidant capacities. The peptide fractions scavenged the 2, 2'-anizo-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radicals and inhibited the activity of reactive oxygen species. Walnut protein hydrolysates were also tested, for the first time, against the viability of human breast (MDA-MB231) and colon (HT-29) cancer cell lines. MTT, [3-(4, 5dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide], assay was used to assess in vitro cancer cell viability upon treatment with the peptide fractions. The peptide fractions showed cell growth inhibition of 63 +/- 1.73 % for breast cancer and 51 +/- 1.45 % for colon cancer cells. Thus, a direct correlation between antioxidant and anticancer activities of walnut peptide fractions exists and supports their potential therapeutic benefit. PMID- 27679442 TI - Pretreatment of Shaoyao Gancao Decoction () alters pharmacokinetics of intravenous paclitaxel in rats. AB - OBJECTIVE: To investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats. METHODS: Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non compartment model using the computer program DAS 2.0. RESULTS: The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC0 t, from 4 820+/-197 to 4 205+/-186 ng.mL-1.-1) and AUC0-infinity (from 5 237+/ 280 to 4 514+/-210 ng.mL-1.-1) significantly decreased in response to the 14-day pretreatment with SGD. The values of Vdss (L/kg) were 10.74+/-1.08 and 9.35+/ 0.49, those of CL (L/kg) were 0.67+/-0.03 and 0.57+/-0.03 and the t1/2 (h) values were 11.17+/-0.84 and 11.32+/-0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUC0-t and AUC0-infinity values decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel. CONCLUSIONS: SGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients. PMID- 27679443 TI - Impact of acupuncture therapy in postoperative aortic dissection patients with cerebral infarction: A case study. PMID- 27679444 TI - Development of Mechanical and Failure Properties in Sheep Cerebral Arteries. AB - Traumatic brain injury (TBI) is a devastating problem for people of all ages, but the nature of the response to such injury is often different in children than in adults. Cerebral vessel damage and dysfunction are common following TBI, but age dependent, large-deformation vessel response has not been characterized. Our objective was to investigate the mechanical properties of cerebral arteries as a function of development. Sheep middle cerebral arteries from four age groups (fetal, newborn, juvenile, and adult) were subjected to biaxial loading around physiological conditions and then to failure in the axial direction. Results show little difference among age groups under physiological loading conditions, but response varied significantly with age in response to large axial deformation. Vessels from all age groups reached the same ultimate stretch level, but the amount of stress carried at a given level of stretch increased significantly with age through the developmental period (fetal to juvenile). Our results are the first to identify changes in cerebral vessel response to large deformations with age and may lead to new insights regarding differences in response to TBI with age. PMID- 27679445 TI - PulmoStent: In Vitro to In Vivo Evaluation of a Tissue Engineered Endobronchial Stent. AB - Currently, there is no optimal treatment available for end stage tumour patients with airway stenosis. The PulmoStent concept aims on overcoming current hurdles in airway stenting by combining a nitinol stent with a nutrient-permeable membrane, which prevents tumour ingrowth. Respiratory epithelial cells can be seeded onto the cover to restore mucociliary clearance. In this study, a novel hand-braided dog bone stent was developed, covered with a polycarbonate urethane nonwoven and mechanically tested. Design and manufacturing of stent and cover were improved in an iterative process according to predefined requirements for permeability and mechanical properties and finally tested in a proof of concept animal study in sheep for up to 24 weeks. In each animal two stents were implanted, one of which was cell-seeded by endoscopic spraying in situ. We demonstrated the suitability of this membrane for our concept by glucose transport testing and in vitro culture of respiratory epithelial cells. In the animal study, no migration occurred in any of the twelve stents. There was only mild granulation tissue formation and tissue reaction; no severe mucus plugging was observed. Thus, the PulmoStent concept might be a step forward for palliative treatment of airway stenosis with a biohybrid stent device. PMID- 27679447 TI - Modeling and Optimization of Airbag Helmets for Preventing Head Injuries in Bicycling. AB - Bicycling is the leading cause of sports-related traumatic brain injury. Most of the current bike helmets are made of expanded polystyrene (EPS) foam and ultimately designed to prevent blunt trauma, e.g., skull fracture. However, these helmets have limited effectiveness in preventing brain injuries. With the availability of high-rate micro-electrical-mechanical systems sensors and high energy density batteries, a new class of helmets, i.e., expandable helmets, can sense an impending collision and expand to protect the head. By allowing softer liner medium and larger helmet sizes, this novel approach in helmet design provides the opportunity to achieve much lower acceleration levels during collision and may reduce the risk of brain injury. In this study, we first develop theoretical frameworks to investigate impact dynamics of current EPS helmets and airbag helmets-as a form of expandable helmet design. We compared our theoretical models with anthropomorphic test dummy drop test experiments. Peak accelerations obtained from these experiments with airbag helmets achieve up to an 8-fold reduction in the risk of concussion compared to standard EPS helmets. Furthermore, we construct an optimization framework for airbag helmets to minimize concussion and severe head injury risks at different impact velocities, while avoiding excessive deformation and bottoming-out. An optimized airbag helmet with 0.12 m thickness at 72 +/- 8 kPa reduces the head injury criterion (HIC) value to 190 +/- 25 at 6.2 m/s head impact velocity compared to a HIC of 1300 with a standard EPS helmet. Based on a correlation with previously reported HIC values in the literature, this airbag helmet design substantially reduces the risks of severe head injury up to 9 m/s. PMID- 27679446 TI - Development of a Smart Pump for Monitoring and Controlling Intraocular Pressure. AB - Animal models of ocular hypertension are important for glaucoma research but come with experimental costs. Available methods of intraocular pressure (IOP) elevation are not always successful, the amplitude and time course of IOP changes are unpredictable and irreversible, and IOP measurement by tonometry is laborious. Here we present a novel system for monitoring and controlling IOP without these limitations. It consists of a cannula implanted in the anterior chamber of the eye, a pressure sensor that continually measures IOP, and a bidirectional pump driven by control circuitry that can infuse or withdraw fluid to hold IOP at user-desired levels. A portable version was developed for tethered use on rats. We show that rat eyes can be cannulated for months without causing significant anatomical or physiological damage although the animal and its eyes freely move. We show that the system measures IOP with <0.7 mmHg resolution and <0.3 mmHg/month drift and can maintain IOP within a user-specified window of desired levels for any duration necessary. We conclude that the system is ready for cage- or bench-side applications. The results lay the foundation for an implantable version that would give glaucoma researchers unprecedented knowledge and control of IOP in rats and potentially larger animals. PMID- 27679448 TI - Treatment Options for Urogenital Dysfunction in Parkinson's Disease. AB - OPINION STATEMENT: Urogenital dysfunction is commonly reported in Parkinson's disease (PD), and history taking and a bladder diary form the cornerstone of evaluation. The assessment of lower urinary tract (LUT) symptoms include urinalysis, ultrasonography, and urodynamic studies and help to evaluate concomitant urological pathologies such as benign prostate enlargement. Antimuscarinic medications are the first line treatment for overactive bladder (OAB) symptoms and solifenacin has been specifically studied in PD. Antimuscarininc drugs may exacerbate PD-related constipation and xerostomia, and caution is advised when using these medications in individuals where cognitive impairment is suspected. Desmopressin is effective for the management of nocturnal polyuria which has been reported to be common in PD. Intradetrusor injections of botulinum toxin have been shown to be effective for detrusor overactivity, however, are associated with the risk of urinary retention. Neuromodulation is a promising, minimally invasive treatment for PD-related OAB symptoms. Erectile dysfunction is commonly reported and first line treatments include phosphodiesterase-5 inhibitors. A patient-tailored approach is required for the optimal management of urogenital dysfunction in PD. PMID- 27679449 TI - A Firefly Algorithm-based Approach for Pseudo-Relevance Feedback: Application to Medical Database. AB - The difficulty of disambiguating the sense of the incomplete and imprecise keywords that are extensively used in the search queries has caused the failure of search systems to retrieve the desired information. One of the most powerful and promising method to overcome this shortcoming and improve the performance of search engines is Query Expansion, whereby the user's original query is augmented by new keywords that best characterize the user's information needs and produce more useful query. In this paper, a new Firefly Algorithm-based approach is proposed to enhance the retrieval effectiveness of query expansion while maintaining low computational complexity. In contrast to the existing literature, the proposed approach uses a Firefly Algorithm to find the best expanded query among a set of expanded query candidates. Moreover, this new approach allows the determination of the length of the expanded query empirically. Experimental results on MEDLINE, the on-line medical information database, show that our proposed approach is more effective and efficient compared to the state-of-the art. PMID- 27679450 TI - Genomic diversity of cercarial clones of Himasthla elongata (Trematoda, Echinostomatidae) determined with AFLP technique. AB - The aim of this study was to reveal genomic diversity formed during parthenogenetic reproduction of rediae of the trematode Himasthla elongata in its molluskan host Littorina littorea. We applied amplification fragment length polymorphism (AFLP) to determine the genomic diversity of individual cercariae within the clone, that is, the infrapopulation of parthenogenetic progeny in a single molluskan host. The level of genomic diversity of particular cercariae isolates from a single clone, detected with EcoR1/Mse1 AFLP reaction, was significantly lower than the variability of cercariae from different clones. The presence of intraclonal genomic diversity indicates a nonsexual shuffle of alleles during parthenogenesis in the rediae of H. elongata. The obtained polymorphic AFLP fragments were long enough to detect the sequences that may be responsible for clonal genomic variability. Based on this, AFLP can be recommended as a tool for the study of genetic mechanisms of this variability. PMID- 27679451 TI - History of schistosomiasis epidemiology, current status, and challenges in China: on the road to schistosomiasis elimination. AB - Schistosomiasis is a snail-borne disease caused by worms of the genus Schistosoma. Worldwide, human schistosomiasis remains a serious public health problem, threatening ~800 million people in 78 countries with a loss of 70 million disability-adjusted life years. Schistosoma japonicum is the only human blood fluke that occurs in China. As one of the countries suffering greatly from schistosomiasis, over the past 65 years, China has made great strides in controlling schistosomiasis, blocking the transmission of S. japonicum in five provinces, remarkably reducing transmission intensities in the other seven endemic provinces, and China is currently preparing to move toward the elimination of this disease before 2025. However, while on the road to schistosomiasis elimination, emerging challenges merit attention, including severe advanced cases, increased movements of population and livestock, large area distribution of intermediate host snails, limitations of new drug developments and no vaccine available, as well as imported schistosomiasis and its potential risk. PMID- 27679452 TI - Traditional herbal remedies and dietary spices from Cameroon as novel sources of larvicides against filariasis mosquitoes? AB - In Cameroon, many dietary spices are used by traditional healers to cure several diseases such as cancer and microbial infections. Aframomum daniellii, Dichrostachys cinerea and Echinops giganteus are Cameroonian spices widely used as flavourings and as food additives. Moreover, they are traditionally herbal remedies employed to treat several diseases, as well as to control populations of insect pests. In this research, we analysed the chemical composition of A. daniellii, D. cinerea and E. giganteus essential oils and we evaluated their larvicidal potential against larvae of the filariasis and West Nile virus vector Culex quinquefasciatus. The essential oils were obtained from different plant parts by hydrodistillation and their composition was analysed by GC-MS. The three spices exhibited different volatile chemical profiles, being characterized by 1,8 cineole, sabinene and beta-pinene (A. daniellii), geraniol and terpinen-4-ol (D. cinerea), and silphiperfol-6-ene and presilphiperfolan-8-ol (E. giganteus). Results showed that the highest larvicidal toxicity on Cx. quinquefasciatus was exerted by D. cinerea essential oil (LC50 = 39.1 MUL L-1), followed by A. daniellii (pericarp essential oil: LC50 = 65.5 MUL L-1; leaves: LC50 = 65.5MUL L 1; seeds: LC50 = 106.5MUL L-1) and E. giganteus (LC50 = 227.4 MUL L-1). Overall, the chance to use the D. cinerea essential oil against Cx. quinquefasciatus young instars seems promising, since it is effective at moderate doses and could be an advantageous alternative to build newer mosquito control tools. PMID- 27679454 TI - The Chiari 3.5 malformation: a review of the only reported case. AB - INTRODUCTION: In 1894, Giuseppe Muscatello described what we believe to be the only case of an occipitocervical encephalocele with a communication to the stomach. This case and its history and context compared to the Chiari 3 malformation as described 3 years earlier by Hans Chiari are presented. CONCLUSIONS: Based on the uniqueness of this case, we propose the term Chiari 3.5 malformation be used to describe its anatomical derailment. PMID- 27679453 TI - Surgical Management of Gynecomastia: Subcutaneous Mastectomy and Liposuction. AB - BACKGROUND: The treatment of gynecomastia depends on multiple factors, and the best modality is controversial. In this study, we aimed to determine the best management approach by comparing outcomes of two groups of patients with gynecomastia who received subcutaneous mastectomy combined with liposuction and liposuction only. METHODS: We conducted a retrospective analysis of 64 patients who underwent surgery for gynecomastia. We divided the patients into two groups: group A, patients who underwent liposuction only; and group B, patients who underwent liposuction and subcutaneous mastectomy. The serial photographs of all patients were clinically evaluated with respect to size, shape, scarring, and overall outcome by three plastic surgeons, and patient satisfaction was surveyed with regard to palpable lumps, size, shape, scarring, and overall outcome. RESULTS: Of the 64 subjects, 16 received liposuction only, and 48 received the combination procedure. A total of 125 breasts were involved. The doctors' scores for size and overall outcome were significantly better in the combination group, whereas scarring was better in the liposuction-only group. Similarly, patient satisfaction regarding size was significantly higher in the combination group, and satisfaction regarding scarring was significantly higher in the liposuction only group. The scores for scarring in the combination treatment group were acceptable. CONCLUSION: Our study shows that combination treatment with liposuction and subcutaneous mastectomy results in satisfactory outcomes, including the extent of scarring. We conclude that this combination treatment should be recommended as the standard surgical treatment for gynecomastia and can provide excellent results in cases where glandular tissue needs to be removed. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27679455 TI - A longitudinal study of the SF-36 version 2 in Friedreich ataxia. AB - OBJECTIVES: The Medical Outcomes Study 36 item Short-Form Health Survey (SF-36) is one of the most commonly used patient reported outcome measure. This study aimed to examine the relationship between SF-36 version 2 (SF-36V2) summary scores and Friedreich ataxia (FRDA) clinical characteristics, and to investigate the responsiveness of the scale, in comparison with the Friedreich Ataxia Rating Scale (FARS), over 1, 2 and 3 years. MATERIALS AND METHODS: Descriptive statistics were used to examine the characteristics of the cohort at baseline and years 1, 2 and 3. Correlations between FRDA clinical characteristics and SF-36V2 summary scores were reported. Responsiveness was measured using paired t tests. RESULTS: We found significant correlations between the physical component summary (PCS) of the SF-36V2 and various FRDA clinical parameters but none for the mental component summary. No significant changes in the SF-36V2 were seen over 1 or 2 years; however, PCS scores at Year 3 were significantly lower than at baseline ( 3.3, SD [7.6], P=.01). FARS scores were found to be significantly greater at Years 1, 2 and 3 when compared to baseline. CONCLUSIONS: Our findings suggest that despite physical decline, individuals with FRDA have relatively stable mental well-being. This study demonstrates that the SF-36V2 is unlikely to be a useful tool for identifying clinical change in FRDA therapeutic trials. PMID- 27679456 TI - Polycyclic aromatic hydrocarbons (PAHs) around tea processing industries using high-sulfur coals. AB - In the present investigation, the concentrations of polycyclic aromatic hydrocarbons (PAHs) associated with PM2.5, PM10 and dust particles emitted from two tea processing industrial units were studied that uses high-sulfur coal as their energy source. A total of 16 PAHs (viz. naphthalene (Nap), acenaphthene (Ace), acenaphthylene (Acen), phenanthrene (Phe), fluorene (Flu), anthracene (Ant), fluoranthene (Fluo), pyrene (Pyr), benz[a]anthracene (BaA), chrysene (Chry), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), dibenz[a,h]anthracene (DBahA), indeno[1,2,3-cd]pyrene (IP) and benzo[ghi]perylene (BghiP) were measured. The total PAH concentration was found to be 94.7 ng/m3 (?4 PAHs) in the PM10 particle, 32.5 (?12 PAHs) in PM2.5 and 1.08 ng/m3 (?6 PAHs) in the dust sample from site A. In site B, the sum of the PAHs in the PM2.5, PM10 and dust samples are found to be 154.4 ng/m3 (?7 PAHs), 165 ng/m3 (?3 PAHs) and 1.27 ng/m3 (?6 PAHs), respectively. Hybrid Single Particle Lagrangian Integrated Trajectory model study revealed the contribution of local or long-range transport of aerosol sources. Along with the coal combustion activities in the study sites, other sources such as biomass burning and vehicular emission may contribute to the PAHs in the aerosol samples. PMID- 27679457 TI - Eavesdropping on cooperative communication within an ant-butterfly mutualism. AB - Signalling is necessary for the maintenance of interspecific mutualisms but is vulnerable to exploitation by eavesdropping. While eavesdropping of intraspecific signals has been studied extensively, such exploitation of interspecific signals has not been widely documented. The juvenile stages of the Australian lycaenid butterfly, Jalmenus evagoras, form an obligate association with several species of attendant ants, including Iridomyrmex mayri. Ants protect the caterpillars and pupae, and in return are rewarded with nutritious secretions. Female and male adult butterflies use ants as signals for oviposition and mate searching, respectively. Our experiments reveal that two natural enemies of J. evagoras, araneid spiders and braconid parasitoid wasps, exploit ant signals as cues for increasing their foraging and oviposition success, respectively. Intriguingly, selection through eavesdropping is unlikely to modify the ant signal. PMID- 27679458 TI - Diethylaminoethyl Sepharose (DEAE-Sepharose) microcolumn for enrichment of glycopeptides. AB - N-Glycosylation is one of the most prevalent protein post-translational modifications and is involved in many biological processes, such as protein folding, cellular communications, and signaling. Alteration of N-glycosylation is closely related to the pathogenesis of diseases. Thus, the investigation of protein N-glycosylation is crucial for the diagnosis and treatment of disease. In this research, we applied diethylaminoethanol (DEAE) Sepharose solid-phase extraction microcolumns for N-glycopeptide enrichment. This method integrated the advantages of Click Maltose and zwitterionic HILIC (ZIC-HILIC) and showed a relatively higher specificity for N-glycosylated peptides. This strategy was then applied to tryptic digests of normal human serum, followed by deglycosylation using peptide-N-glycosidase F (PNGase F) in H218O. Subsequent LC-MS/MS analysis allowed for the assignment of 219 N-glycosylation sites from 115 serum N glycoproteins. This study provides an alternative approach for N-glycopeptide enrichment and the method employed is effective for large-scale N-glycosylation site identification. Graphical abstract Proposed mechanism of glycopeptides enrichment using DEAE-Sepharose. PMID- 27679459 TI - A decade of natalizumab and PML: Has there been a tacit transfer of risk acceptance? AB - The interplay between each of the stakeholder's responsibilities and desires clearly has resulted in continued widespread use of natalizumab with substantial risks and an ongoing quest for better risk mitigation. In the United States, regulatory actions codified the process of risk acceptance-and risk transfer-by escalating monitoring and information transfer to physicians and patients. Management of medication-related risks is a core function of regulatory agencies such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the medical community. The interaction among stakeholders in medicine, pharma, regulatory bodies, physicians, and patients, sometimes has changed without overt review and discussion. Such is the case for natalizumab, an important and widely used disease-modifying therapy for multiple sclerosis. A rather silent but very considerable shift, effectively transferring increased risk for progressive multifocal leukoencephalopathy (PML) to the physicians and patients, has occurred in the past decade. We believe this changed risk should be clearly recognized and considered by all the stakeholders. PMID- 27679460 TI - Gadopentetate but not gadobutrol accumulates in the dentate nucleus of multiple sclerosis patients. AB - BACKGROUND: Previous studies have postulated an association between dentate nucleus T1 hyperintensity and multiple sclerosis (MS)-related progressive neurodegeneration. Therefore, MS patients have been excluded from most studies investigating brain deposition of gadolinium-based contrast agents (GBCAs). OBJECTIVE: To study the hypothesis that dentate nucleus T1 hyperintensity in MS patients is associated with GBCA administration. METHODS: In a cohort of 97 MS patients, the dentate-to-pons signal intensity ratio (DPSIR) was calculated for 265 consecutive T1-weighted magnetic resonance (MR) scans (including sessions with and without the administration of GBCA). Patients exclusively received either gadopentetate dimeglumine (Gd-DTPA, linear) or gadobutrol (Gd-BT-DO3A, macrocyclic). RESULTS: In patients receiving Gd-DTPA, DPSIR increased significantly between the first and the last scan (+0.009, p < 0.001), and following magnetic resonance imaging (MRI) with Gd-DTPA administration as compared to following an MRI without Gd-DTPA administration (+0.005 vs -0.001; p = 0.022). Additionally, there was a positive linear relationship between the number of Gd-DTPA administrations and the increase in DPSIR ( p = 0.017). No DPSIR increase was observed after Gd-BT-DO3A administration. CONCLUSION: Dentate nucleus T1 hyperintensity in MS patients is associated with Gd-DTPA (but not Gd BT-DO3A) administration, suggesting an alternative explanation for the association of T1 hyperintensity with disease duration and severity. PMID- 27679461 TI - Overlapping Group Logistic Regression with Applications to Genetic Pathway Selection. AB - Discovering important genes that account for the phenotype of interest has long been a challenge in genome-wide expression analysis. Analyses such as gene set enrichment analysis (GSEA) that incorporate pathway information have become widespread in hypothesis testing, but pathway-based approaches have been largely absent from regression methods due to the challenges of dealing with overlapping pathways and the resulting lack of available software. The R package grpreg is widely used to fit group lasso and other group-penalized regression models; in this study, we develop an extension, grpregOverlap, to allow for overlapping group structure using a latent variable approach. We compare this approach to the ordinary lasso and to GSEA using both simulated and real data. We find that incorporation of prior pathway information can substantially improve the accuracy of gene expression classifiers, and we shed light on several ways in which hypothesis-testing approaches such as GSEA differ from regression approaches with respect to the analysis of pathway data. PMID- 27679463 TI - Comparison of Personal Resources in Patients Who Differently Estimate the Impact of Multiple Sclerosis. AB - BACKGROUND: Discrepancies between physicians' assessment and patients' subjective representations of the disease severity may influence physician-patient communication and management of a chronic illness, such as multiple sclerosis (MS). For these reasons, it is important to recognize factors that distinguish patients who differently estimate the impact of MS. PURPOSE: The purpose of this study was to verify if the patients who overestimate or underestimate the impact of MS differ in their perception of personal resources from individuals presenting with a realistic appraisal of their physical condition. METHODS: A total of 172 women and 92 men diagnosed with MS completed Multiple Sclerosis Impact Scale, University of Washington Self Efficacy Scale, Rosenberg Self-Esteem Scale, Body Esteem Scale, Brief Illness Perception Questionnaire, Treatment Beliefs Scale, Actually Received Support Scale, and Socioeconomic resources scale. Physician's assessment of health status was determined with Expanded Disability Status Scale. RESULTS: Linear regression analysis was conducted to identify the subsets of patients with various patterns of subjective health and Expanded Disability Status Scale (EDSS) scores. Patients overestimating the impact of their disease presented with significantly lower levels of self-esteem, self-efficacy in MS, and body esteem; furthermore, they perceived their condition more threatening than did realists and underestimators. They also assessed anti MS treatment worse, had less socioeconomic resources, and received less support than underestimators. Additionally, underestimators presented with significantly better perception of their disease, self, and body than did realists. CONCLUSION: Self-assessment of MS-related symptoms is associated with specific perception of personal resources in coping with the disease. These findings may facilitate communication with patients and point to new directions for future research on adaptation to MS. PMID- 27679462 TI - Sleep Habits and Susceptibility to Upper Respiratory Illness: the Moderating Role of Subjective Socioeconomic Status. AB - BACKGROUND: Sleep is a predictor of infectious illness that may depend on one's socioeconomic status (SES). PURPOSE: This study aimed to investigate the moderating effects of objective and subjective SES on sleep-clinical cold risk link and test whether nasal inflammation serves as a plausible biological pathway. METHODS: This study combined data (n = 732) from three viral challenge studies. Measures of self-reported sleep and objective and subjective measures of SES were obtained. Participants were quarantined and administrated rhinovirus (RV) or influenza virus and monitored over 5 (RV) or 6 (influenza) days for the development of a cold. Symptom severity, including mucus production and nasal clearance time, and levels of nasal cytokines (interleukin (IL)-6 and IL-1beta) were measured prior to administration and each day during the quarantined period. RESULTS: Subjective SES, but not objective SES, moderated associations between shorter sleep duration and increased likelihood of a clinical cold. Compared to >=8-hour sleepers, <=6-hour sleepers with low subjective SES were at increased risk for developing a cold (OR = 2.57, 95% CI 1.10-6.02). There was no association between sleep duration and colds in high subjective SES participants. Among infected individuals who reported low subjective SES, shorter sleep duration was associated with greater mucus production. There was no evidence that markers of nasal inflammation mediated the link between sleep duration and cold susceptibility among those reporting low subjective SES. CONCLUSION: Subjective SES may reflect an important social factor for understanding vulnerability to and protection against infectious illness among short sleepers. PMID- 27679465 TI - Carcinosarcoma of the ampulla of Vater: a case report and literature review. AB - BACKGROUND: Carcinosarcoma of the ampulla of Vater is extremely rare, and to the best of our knowledge, this is the third reported study. CASE PRESENTATION: The patient was a 73-year-old man, who presented with a chief complaint of dark urine. After a work-up, we suspected duodenal papillary cancer and performed a subtotal stomach-preserving pancreaticoduodenectomy with lymph node dissection. Immunohistochemically, the sarcomatous atypical cells were diffusely positive for cytokeratin AE1&3 and vimentin and focally positive for alpha-smooth muscle actin; these cells were also negative for desmin, CD34, DOG1, c-kit, and S100. From these findings, we diagnosed the patient with so-called carcinosarcoma. There was no lymph node metastasis. CONCLUSIONS: Carcinosarcoma of the ampulla of Vater has a poor prognosis, and lymph node metastases are often seen. For the complete cure of carcinosarcoma of the ampulla of Vater, resection with the dissection of the lymph nodes may be necessary. PMID- 27679466 TI - Spontaneous biliary peritonitis with common bile duct stones: report of a case. AB - Spontaneous biliary peritonitis is rare in adults. We herein report a case of spontaneous biliary peritonitis. An 84-year-old man was admitted to our hospital for abdominal pain for 5 days. He developed fever, jaundice, and abdominal rigidity. Computed tomography (CT) revealed massive ascites in the omental bursa and around the liver. The ascites obtained by diagnostic paracentesis was dark yellow-green in color, which implied bile leakage. With a diagnosis of bile peritonitis, the patient underwent emergency exploratory laparotomy. There was massive biliary ascites in the abdominal cavity, especially in the omental bursa. Because exploration failed to demonstrate the perforation site in the gallbladder and biliary duct, we performed abdominal lavage alone. Postoperative endoscopic retrograde cholangiopancreatography showed stones in the common bile duct, and there was no evidence of biliary leakage. Endoscopic retrograde biliary drainage was performed using a plastic stent to reduce the pressure of the common bile duct. After the operation, the patient showed satisfactory recovery and started oral intake on postoperative day 8. However, the patient developed heart failure due to renal dysfunction with nephrotic syndrome at 1 month after the operation. With a diagnosis of rapidly progressive glomerulonephritis due to immune complex, the patient received steroid treatment for nephritis, diuretics, and carperitide for heart failure. Although heart failure and renal dysfunction improved by these treatment, the patients developed toxic epidermal necrolysis which was refractory to intensive treatments including steroid pulse and immunoglobulin, and the patient died 76 days after the operation. PMID- 27679464 TI - Attachment Orientations, Respiratory Sinus Arrhythmia, and Stress Are Important for Understanding the Link Between Childhood Socioeconomic Status and Adult Self Reported Health. AB - BACKGROUND: Low childhood socioeconomic status (SES) is reliably associated with poor adult health. Social environments early in life and physiological stress responses are theorized to underlie this link; however, the role of attachment orientations is relatively unknown. PURPOSE: In this study, we examined whether attachment orientations (i.e., attachment anxiety and attachment avoidance) and self-reported stress were mediators of the association between childhood SES and self-reported health in adulthood. Furthermore, we examined whether parasympathetic nervous system functioning was a moderator of associations between attachment orientations and self-reported stress. METHODS: Participants (N = 213) provided self-reports of childhood SES, attachment orientations, general stress, and self-rated health. Respiratory sinus arrhythmia (RSA) was measured at rest, as well as during an acute social stressor. RESULTS: Low childhood SES was associated with poor self-reported health via the serial pathway from attachment anxiety to general stress. Moreover, attachment avoidance was associated with self-reported health via general stress, but only among those with high stress-induced RSA. Findings were independent of participant age, sex, race, body mass index, baseline RSA, and adult SES. CONCLUSIONS: Attachment theory is useful for understanding why those from low SES backgrounds are at greater risk of negative health outcomes in adulthood. Findings extend our knowledge of how interpersonal relationships in childhood can shape emotional and physical health outcomes in adulthood. PMID- 27679467 TI - A Social History of Ascariasis in the 1960s Korea : From a Norm to a Shameful Disease. AB - Until the 1950s, Ascaris was regarded as an essential part of life which controls every aspect of human physiology among Koreans. Therefore, Ascaris should not be removed from human body. Efforts from medical professionals and the Korean government officials who wished to push forward the parasite control program, had to constantly contest with this perception of Ascaris among ordinary Koreans. In 1966, the 'Parasitic Disease Prevention Act' was promulgated and 'the Korean Association for Parasite Eradication (KAPE)' established in Korea. From the 1970s, Korea mobilized 15 million people each year to achieve the eradication goal. Such mass mobilization could not be possible without public awareness on necessity of parasite eradication. Until the early 1960s, however, Korean people were not sympathetic to the needs of eradication of parasites, especially that of Ascaris. Then, what changed the social perception towards Ascaris during the 1960s? What contributing factors allowed the mass mobilization and public involvement for that campaign? Employing newspaper articles and periodicals, this paper analyzes how social perception on Ascariasis changed during the 1960s, when the 'Parasitic Disease Prevention Act' was established. During the 1960s, Ascariasis became a shameful disease for Koreans. A series of events made Ascariasis more visible and shameful to Koreans. First event happened with Korean miners who were dispatched to Germany in 1963. When the miners turned out to have been infected with intestinal parasites, they were prohibited from work at the mines by the authorities in Germany and quarantined for several weeks. This humiliating experience of Korean expatriate people having bodies swarmed with parasites became a national shame to Koreans. The parasite infected bodies of Korean workers were revealed to the World through German newspapers. Second event happened when a child died of intestinal obstruction due to Ascariasis. The doctor retrieved 1,063 Ascaris from the bowel of the 9 year-old girl, and the photo of the 1,063 worms was published in several newspapers. It was a shocking visualization of Ascariasis in Korean society. Through these visualizations of Ascariasis, the Korean society began to perceive Ascariasis as a shame of the nation as well as that of an individual. PMID- 27679468 TI - The Food Hygiene Institutionalization of Park Junghee Government in 1960s. AB - This article investigates the historical background and distinctive characteristics of the Korean food hygiene policy during the 1960s. The 3 main findings of this study are as follows. First, Food Sanitation Law in the 1960s was established too hastily and thus mistakenly accommodated two discordant laws as American style law and empire of Japan style law. The legislation of Food Sanitation Law was progressed too quickly for the justification purpose of 5.16 military coup, as one of reorganization tasks of the Korean legal structure established under Japanese imperialism, Second, a division in charge of food hygiene in the Ministry of Health and Social Affairs was newly installed in 1967, as an outcome reflecting a variety of social demand, at least, minimally. Rongalite shock in Korea prompted diverse suggestions for preventing unfortunate accidents from toxic and harmful food. However, Korean Government did not provide the division with necessary budget and manpower to implement relevant regulations. Third, "the special law against health crimes" legislated in 1969, was characterized by severe punishment policy which might be performed afterward but not by protective measures against accidents in advance. The law enabled regulators to punish corrupt dealers up to life sentence. For the constitutional amendment for President for the third term, Park Chung-hee's regime tried to calm down the complaints of people. In sum, the regulations of Korean food hygiene in the 1960s were identified as government practices using an interesting combination of low costs and severe punishments. PMID- 27679469 TI - Cooperation and Conflict: Faction Problem of Western Medicine Group in Modern China. AB - After the defeat of the Opium War and the Sino-Japanese War, China's intellectuals realized necessity of modernization (Westernization) to survive in the imperial order of the survival of the fittest. In particular, it was urgent to accept Western medicine and train the doctors who learned Western medicine to change the sick and weary Chinese to be robust. Thus, new occupations of the Western Medicine Group (xiyi, doctors who learned Western medicine) emerged in China. As with the first profession, the new Western Medicine Group tried to define standards of Western medicine and medical profession; however, it was difficult in the absence of the strong central government. In addition, they formed a faction by the country where they studied or the language they learned. The factions included the Britain - America faction(yingmeipai) consisting of the Britain - America studied doctors or graduates from Protestant missions based medical schools, and the Germany - Japan faction(deripai), graduates from medical schools by Japanese or German government and the Chinese government. In 1915, they founded the National Medical Association of China mainly consisting of the Britain - America faction and the National Medical and Pharmaceutical Association of China led by the Germany - Japan faction. Initially, exchanges were active so most of eminent doctors belonged the two associations at the same time. They had a consciousness of a common occupation group as a doctor who had learned Western medicine. Thus, they actively cooperated to keep their profits against Chinese medicine and enjoy their reputation. Their cooperation emitted light particularly in translation of medical terms and unified works. Thanks to cooperation, the two associations selected medical terminologies by properly using the cases of the West and Japan. Additionally, medical schools of the Britain - America faction and the Germany - Japan faction produced various levels of the Western Medicine Group doctors for China to timely respond to the rapidly increased demand. However, a conflict over the promotion of hygiene administration and the unification, organization of medical education did not end. This conflict was deepening as the Nanjing nationalist government promoted sanitary administration. It was the Britain - America faction who seized a chance of victory. It was because figures from the Britain - America faction held important positions in the hygiene department. Of course, some related to the National Medical and Pharmaceutical Association of China were also involved in the hygiene department; however, most took charge of simple technical tasks, not having a significant impact on hygiene administration. To solve the problem of factions of the Western Medicine Group, the Britain - America faction or the Germany - Japan faction had to arrange the education system with a strong power, or to organize a new association of two factions mixed, as in Chinese faction(zhonghuapai). But an effort of the Britain - America faction to unify the systems of medical schools did not reach the Germany - Japan faction's medical schools. Additionally, from 1928, executives of the two Chinese medical associations discussed their merger; however they could not agree because of practitioners'interests involved. Substantially, a conflict between factions of the Western Medicine Group continued even until the mid-1930s. This implies that the then Chinese government had a lack of capacity of uniting and organizing the medical community. PMID- 27679470 TI - The Perception of Ginseng in England and America, 1600-1800. AB - This paper aims to redress serious imbalances in the research on ginseng. Most accounts of ginseng treat it as an exclusively East Asian commodity, and are dominated by the natural sciences. Ginseng, however, was much discussed in England and America in the early modern period: the discussion encompassed not only botanical and medical interests, but also discourses on the commercial marketability of ginseng; ginseng was also an item that embodied European prejudices, symbolizing perceived 'differences' between the West and East. As such, ginseng was an 'indigenous' item of 'the East' that was much discussed in 'the West', but one that resisted assimilation into its systems of knowledge. PMID- 27679471 TI - Adalimumab effectiveness in Behcet's disease: short and long-term data from a multicenter retrospective observational study. AB - Our aim was to evaluate the effectiveness of adalimumab (ADA) during a 24-month study period in patients affected with Behcet's disease (BD). Clinical and therapeutic data from 100 consecutive BD patients treated with ADA were retrospectively collected and statistically analyzed. At 12-week follow-up, ADA induced clinical efficacy in 81 patients, with a mean time to response of 7.63 +/ 3.43 weeks; 25 (30.9 %) patients underwent a disease relapse after 22.17 +/- 1.57 months, but treatment adjustments allowed a recovery of efficacy in 11 cases. At 24-month follow-up, 67/100 patients were still on ADA therapy despite concomitant treatments. No differences were identified between ADA monotherapy and co-treatment with DMARDs about efficacy (p = 0.09), time to response (p = 0.61), relapses (p = 0.36), and ADA discontinuation (p = 0.40). No differences existed in patients switched from other tumor necrosis factor (TNF)-alpha inhibitors about efficacy at 12 weeks (p = 0.13) and rapidity of response (p = 0.93) while relapses (p = 0.01) and ADA discontinuation at 24 months (p = 0.001) were significantly more common. Adverse events occurred in 10 patients. ADA confirmed its effectiveness in BD. Combination therapy with DMARDs seems not significantly superior to monotherapy. Frequency and time to response for ADA was not conditioned by a previous lack or loss of efficacy to other TNF-alpha inhibitors, but long-term loss of efficacy seemed more likely in patients switched from other anti-TNF agents. PMID- 27679472 TI - Discontinuing colchicine in symptomatic carriers for MEFV (Mediterranean FeVer) variants. AB - Familial Mediterranean fever (FMF) is inherited autosomal recessively; however, heterozygotes may express FMF phenotype. We aimed to define the characteristics of FMF patients heterozygous for MEFV (MEditerranean FeVer) mutations in whom colchicine was stopped after a period of treatment, with close follow-up. We reviewed the charts of 182 children who were heterozygous for MEFV variants. We excluded the patients (n = 34) heterozygous for MEFV variants of unknown significance and patients with typical periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (n = 2). All patients were followed up with their routine analysis and serum amyloid A levels every 6 months while on colchicine treatment and every 3-6 months thereafter. MEFV gene variant analysis was performed with Sanger sequencing. Twenty-two out of 146 heterozygotes initially had FMF phenotype, but colchicine was discontinued after a treatment period. The most common MEFV variant was M694V (86.3 %). The median age at diagnosis/initiation of colchicine was 76 (24-144) months. The median duration of colchicine treatment was 36 (24-110) months. The median age at colchicine cessation was 120 (55-172) months. At the time of colchicine cessation, the median attack- and inflammation-free period was 27 (24-84) months. The median follow-up after colchicine cessation was 22.5 (6-102) months. We re-started colchicine in only two patients because of recurrence of symptoms. Individuals with one mutation only can display FMF phenotype and require colchicine for the clinical and laboratory inflammation. However, in some of these patients, colchicine may be discontinued with very careful follow-up. PMID- 27679473 TI - Bone edema of the whole vertebral body: an unusual case of spondyloarthritis. AB - Spondyloarthritis (SpA) is usually characterized by early inflammatory involvement of the sacroiliac joints (SI), which constitutes one of the most important classification criteria according to the SpondyloArthritis International Society (ASAS). These criteria do not include inflammatory spine lesions which can be detected on MRI, although spine involvement is very common in axial SpA. This is because spine MRI lesion often retrieved in SpA are not very specific, and can be found in many other diseases such as malignancy and osteoarthritis. Here we present the case of a 33-year old woman who presented a worsening low back pain, with a thoracic spine MRI showing bone marrow edema (BME) of the whole T8 vertebral body. Owing to this peculiar presentation, together with the unresponsiveness of the pain to nonsteroidal anti inflammatory drugs (NSAIDs) and a slight increase of the biomarker CA19-9, a malignancy was suspected. Therefore, the patient underwent bone scintigraphy, Single positron emission computed tomography (SPET/TC), positron emission tomography and repeated MRI without reaching a diagnosis. Finally, when SI joints MRI was performed, BME of the SI joints emerged: this was fundamental to formulate the diagnosis of axSpA. PMID- 27679474 TI - hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA. AB - The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal La module binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear. We report the solution NMR structure of the hLARP7 CTD and show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3' end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function. PMID- 27679477 TI - COEXPEDIA: exploring biomedical hypotheses via co-expressions associated with medical subject headings (MeSH). AB - The use of high-throughput array and sequencing technologies has produced unprecedented amounts of gene expression data in central public depositories, including the Gene Expression Omnibus (GEO). The immense amount of expression data in GEO provides both vast research opportunities and data analysis challenges. Co-expression analysis of high-dimensional expression data has proven effective for the study of gene functions, and several co-expression databases have been developed. Here, we present a new co-expression database, COEXPEDIA (www.coexpedia.org), which is distinctive from other co-expression databases in three aspects: (i) it contains only co-functional co-expressions that passed a rigorous statistical assessment for functional association, (ii) the co expressions were inferred from individual studies, each of which was designed to investigate gene functions with respect to a particular biomedical context such as a disease and (iii) the co-expressions are associated with medical subject headings (MeSH) that provide biomedical information for anatomical, disease, and chemical relevance. COEXPEDIA currently contains approximately eight million co expressions inferred from 384 and 248 GEO series for humans and mice, respectively. We describe how these MeSH-associated co-expressions enable the identification of diseases and drugs previously unknown to be related to a gene or a gene group of interest. PMID- 27679476 TI - H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication. AB - DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two pre-replicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase delta, but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex. PMID- 27679478 TI - Influenza Research Database: An integrated bioinformatics resource for influenza virus research. AB - The Influenza Research Database (IRD) is a U.S. National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Bioinformatics Resource Center dedicated to providing bioinformatics support for influenza virus research. IRD facilitates the research and development of vaccines, diagnostics and therapeutics against influenza virus by providing a comprehensive collection of influenza-related data integrated from various sources, a growing suite of analysis and visualization tools for data mining and hypothesis generation, personal workbench spaces for data storage and sharing, and active user community support. Here, we describe the recent improvements in IRD including the use of cloud and high performance computing resources, analysis and visualization of user-provided sequence data with associated metadata, predictions of novel variant proteins, annotations of phenotype-associated sequence markers and their predicted phenotypic effects, hemagglutinin (HA) clade classifications, an automated tool for HA subtype numbering conversion, linkouts to disease event data and the addition of host factor and antiviral drug components. All data and tools are freely available without restriction from the IRD website at https://www.fludb.org. PMID- 27679479 TI - DNA-linked Inhibitor Antibody Assay (DIANA) for sensitive and selective enzyme detection and inhibitor screening. AB - Human diseases are often diagnosed by determining levels of relevant enzymes and treated by enzyme inhibitors. We describe an assay suitable for both ultrasensitive enzyme quantification and quantitative inhibitor screening with unpurified enzymes. In the DNA-linked Inhibitor ANtibody Assay (DIANA), the target enzyme is captured by an immobilized antibody, probed with a small molecule inhibitor attached to a reporter DNA and detected by quantitative PCR. We validate the approach using the putative cancer markers prostate-specific membrane antigen and carbonic anhydrase IX. We show that DIANA has a linear range of up to six logs and it selectively detects zeptomoles of targets in complex biological samples. DIANA's wide dynamic range permits determination of target enzyme inhibition constants using a single inhibitor concentration. DIANA also enables quantitative screening of small-molecule enzyme inhibitors using microliters of human blood serum containing picograms of target enzyme. DIANA's performance characteristics make it a superior tool for disease detection and drug discovery. PMID- 27679480 TI - Finding approximate gene clusters with Gecko 3. AB - Gene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often make restrictive assumptions such as short perfect conservation, conserved gene order or monophyletic gene clusters. We present Gecko 3, an open-source software for finding gene clusters in hundreds of bacterial genomes, that comes with an easy-to-use graphical user interface. The underlying gene cluster model is intuitive, can cope with low degrees of conservation as well as misannotations and is complemented by a sound statistical evaluation. To evaluate the biological benefit of Gecko 3 and to exemplify our method, we search for gene clusters in a dataset of 678 bacterial genomes using Synechocystis sp. PCC 6803 as a reference. We confirm detected gene clusters reviewing the literature and comparing them to a database of operons; we detect two novel clusters, which were confirmed by publicly available experimental RNA Seq data. The computational analysis is carried out on a laptop computer in <40 min. PMID- 27679481 TI - A de novo compound targeting alpha-synuclein improves deficits in models of Parkinson's disease. AB - Abnormal accumulation and propagation of the neuronal protein alpha-synuclein has been hypothesized to underlie the pathogenesis of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Here we report a de novo-developed compound (NPT100-18A) that reduces alpha-synuclein toxicity through a novel mechanism that involves displacing alpha-synuclein from the membrane. This compound interacts with a domain in the C-terminus of alpha-synuclein. The E83R mutation reduces the compound interaction with the 80-90 amino acid region of alpha-synuclein and prevents the effects of NPT100-18A. In vitro studies showed that NPT100-18A reduced the formation of wild-type alpha-synuclein oligomers in membranes, reduced the neuronal accumulation of alpha-synuclein, and decreased markers of cell toxicity. In vivo studies were conducted in three different alpha synuclein transgenic rodent models. Treatment with NPT100-18A ameliorated motor deficits in mThy1 wild-type alpha-synuclein transgenic mice in a dose-dependent manner at two independent institutions. Neuropathological examination showed that NPT100-18A decreased the accumulation of proteinase K-resistant alpha-synuclein aggregates in the CNS and was accompanied by the normalization of neuronal and inflammatory markers. These results were confirmed in a mutant line of alpha synuclein transgenic mice that is prone to generate oligomers. In vivo imaging studies of alpha-synuclein-GFP transgenic mice using two-photon microscopy showed that NPT100-18A reduced the cortical synaptic accumulation of alpha-synuclein within 1 h post-administration. Taken together, these studies support the notion that altering the interaction of alpha-synuclein with the membrane might be a feasible therapeutic approach for developing new disease-modifying treatments of Parkinson's disease and other synucleinopathies. PMID- 27679484 TI - Nausea in early pregnancy is linked to low risk of loss. PMID- 27679482 TI - Exosome secretion is a key pathway for clearance of pathological TDP-43. AB - Cytoplasmic TDP-43 aggregation is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Here we investigated the role of exosomes in the secretion and propagation of TDP-43 aggregates. TDP-43 was detected in secreted exosomes from Neuro2a cells and primary neurons but not from astrocytes or microglia. Evidence is presented that protein aggregation and autophagy inhibition are factors that promote exosomal secretion of TDP-43. We also report that levels of exosomal TDP-43 full length and C-terminal fragment species are upregulated in human amyotrophic lateral sclerosis brains. Exposure of Neuro2a cells to exosomes from amyotrophic lateral sclerosis brain, but not from control brain, caused cytoplasmic redistribution of TDP-43, suggesting that secreted exosomes might contribute to propagation of TDP-43 proteinopathy. Yet, inhibition of exosome secretion by inactivation of neutral sphingomyelinase 2 with GW4869 or by silencing RAB27A provoked formation of TDP-43 aggregates in Neuro2a cells. Moreover, administration of GW4869 exacerbated the disease phenotypes of transgenic mice expressing human TDP-43A315T mutant. Thus, even though results suggest that exosomes containing pathological TDP-43 may play a key role in the propagation of TDP-43 proteinopathy, a therapeutic strategy for amyotrophic lateral sclerosis based on inhibition of exosome production would seem inappropriate, as in vivo data suggest that exosome secretion plays an overall beneficial role in neuronal clearance of pathological TDP-43. PMID- 27679483 TI - Your perspective and my benefit: multiple lesion models of self-other integration strategies during social bargaining. AB - Recursive social decision-making requires the use of flexible, context-sensitive long-term strategies for negotiation. To succeed in social bargaining, participants' own perspectives must be dynamically integrated with those of interactors to maximize self-benefits and adapt to the other's preferences, respectively. This is a prerequisite to develop a successful long-term self-other integration strategy. While such form of strategic interaction is critical to social decision-making, little is known about its neurocognitive correlates. To bridge this gap, we analysed social bargaining behaviour in relation to its structural neural correlates, ongoing brain dynamics (oscillations and related source space), and functional connectivity signatures in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal stroke: behavioural variant frontotemporal dementia, Alzheimer's disease, and frontal lesions. All groups showed preserved basic bargaining indexes. However, impaired self-other integration strategy was found in patients with behavioural variant frontotemporal dementia and frontal lesions, suggesting that social bargaining critically depends on the integrity of prefrontal regions. Also, associations between behavioural performance and data from voxel-based morphometry and voxel-based lesion-symptom mapping revealed a critical role of prefrontal regions in value integration and strategic decisions for self-other integration strategy. Furthermore, as shown by measures of brain dynamics and related sources during the task, the self-other integration strategy was predicted by brain anticipatory activity (alpha/beta oscillations with sources in frontotemporal regions) associated with expectations about others' decisions. This pattern was reduced in all clinical groups, with greater impairments in behavioural variant frontotemporal dementia and frontal lesions than Alzheimer's disease. Finally, connectivity analysis from functional magnetic resonance imaging evidenced a fronto-temporo-parietal network involved in successful self other integration strategy, with selective compromise of long-distance connections in frontal disorders. In sum, this work provides unprecedented evidence of convergent behavioural and neurocognitive signatures of strategic social bargaining in different lesion models. Our findings offer new insights into the critical roles of prefrontal hubs and associated temporo-parietal networks for strategic social negotiation. PMID- 27679485 TI - A Novel Function of delta Factor from Bacillus subtilis as a Transcriptional Repressor. AB - delta, a small protein found in most Gram-positive bacteria was, for a long time, thought to be a subunit of RNA polymerase (RNAP) and was shown to be involved in recycling of RNAP at the end of each round of transcription. However, how delta participates in both up-regulation and down-regulation of genes in vivo remains unclear. We have recently shown, in addition to the recycling of RNAP, delta functions as a transcriptional activator by binding to an A-rich sequence located immediately upstream of the -35 element, consequently facilitating the open complex formation. The result had explained the mechanism of up-regulation of the genes by delta. Here, we show that Bacillus subtilis delta could also function as a transcriptional repressor. Our results demonstrate that delta binds to an A rich sequence located near the -35 element of the spo0B promoter, the gene involved in the regulatory cascade of bacterial sporulation and inhibits the open complex formation due to steric clash with sigma region 4.2. We observed a significant increase in the mRNA level of the spo0B gene in a delta-knock-out strain of B. subtilis compared with the wild-type. Thus, the results report a novel function of delta, and suggest the mechanism of down-regulation of genes in vivo by the protein. PMID- 27679486 TI - Identification of Small Molecule Inhibitors of Human Cytochrome c Oxidase That Target Chemoresistant Glioma Cells. AB - The enzyme cytochrome c oxidase (CcO) or complex IV (EC 1.9.3.1) is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes than those with low tumor CcO activity. Therefore, CcO is an attractive target for cancer therapy. We report here the characterization of a CcO inhibitor (ADDA 5) that was identified using a high throughput screening paradigm. ADDA 5 demonstrated specificity for CcO, with no inhibition of other mitochondrial complexes or other relevant enzymes, and biochemical characterization showed that this compound is a non-competitive inhibitor of cytochrome c When tested in cellular assays, ADDA 5 dose-dependently inhibited the proliferation of chemosensitive and chemoresistant glioma cells but did not display toxicity against non-cancer cells. Furthermore, treatment with ADDA 5 led to significant inhibition of tumor growth in flank xenograft mouse models. Importantly, ADDA 5 inhibited CcO activity and blocked cell proliferation and neurosphere formation in cultures of glioma stem cells, the cells implicated in tumor recurrence and resistance to therapy in patients with glioblastoma. In summary, we have identified ADDA 5 as a lead CcO inhibitor for further optimization as a novel approach for the treatment of glioblastoma and related cancers. PMID- 27679487 TI - Structural and Functional Characterization of a Ruminal beta-Glycosidase Defines a Novel Subfamily of Glycoside Hydrolase Family 3 with Permuted Domain Topology. AB - Metagenomics has opened up a vast pool of genes for putative, yet uncharacterized, enzymes. It widens our knowledge on the enzyme diversity world and discloses new families for which a clear classification is still needed, as is exemplified by glycoside hydrolase family-3 (GH3) proteins. Herein, we describe a GH3 enzyme (GlyA1) from resident microbial communities in strained ruminal fluid. The enzyme is a beta-glucosidase/beta-xylosidase that also shows beta-galactosidase, beta-fucosidase, alpha-arabinofuranosidase, and alpha arabinopyranosidase activities. Short cello- and xylo-oligosaccharides, sophorose and gentibiose, are among the preferred substrates, with the large polysaccharide lichenan also being hydrolyzed by GlyA1 The determination of the crystal structure of the enzyme in combination with deletion and site-directed mutagenesis allowed identification of its unusual domain composition and the active site architecture. Complexes of GlyA1 with glucose, galactose, and xylose allowed picturing the catalytic pocket and illustrated the molecular basis of the substrate specificity. A hydrophobic platform defined by residues Trp-711 and Trp 106, located in a highly mobile loop, appears able to allocate differently beta linked bioses. GlyA1 includes an additional C-terminal domain previously unobserved in GH3 members, but crystallization of the full-length enzyme was unsuccessful. Therefore, small angle x-ray experiments have been performed to investigate the molecular flexibility and overall putative shape. This study provided evidence that GlyA1 defines a new subfamily of GH3 proteins with a novel permuted domain topology. Phylogenetic analysis indicates that this topology is associated with microbes inhabiting the digestive tracts of ruminants and other animals, feeding on chemically diverse plant polymeric materials. PMID- 27679488 TI - Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide: MECHANISTIC DETAILS STUDIED BY SPECTROSCOPY IN COMBINATION WITH MICROSCOPY. AB - The aggregation of insulin into amyloid fibers has been a limiting factor in the development of fast acting insulin analogues, creating a demand for excipients that limit aggregation. Despite the potential demand, inhibitors specifically targeting insulin have been few in number. Here we report a non-toxic and serum stable-designed heptapeptide, KR7 (KPWWPRR-NH2), that differs significantly from the primarily hydrophobic sequences that have been previously used to interfere with insulin amyloid fibrillation. Thioflavin T fluorescence assays, circular dichroism spectroscopy, and one-dimensional proton NMR experiments suggest KR7 primarily targets the fiber elongation step with little effect on the early oligomerization steps in the lag time period. From confocal fluorescence and atomic force microscopy experiments, the net result appears to be the arrest of aggregation in an early, non-fibrillar aggregation stage. This mechanism is noticeably different from previous peptide-based inhibitors, which have primarily shifted the lag time with little effect on later stages of aggregation. As insulin is an important model system for understanding protein aggregation, the new peptide may be an important tool for understanding peptide-based inhibition of amyloid formation. PMID- 27679489 TI - Thrombin Cleavage of Inter-alpha-inhibitor Heavy Chain 1 Regulates Leukocyte Binding to an Inflammatory Hyaluronan Matrix. AB - Dynamic alterations of the extracellular matrix in response to injury directly modulate inflammation and consequently the promotion and resolution of disease. During inflammation, hyaluronan (HA) is increased at sites of inflammation where it may be covalently modified with the heavy chains (HC) of inter-alpha-trypsin inhibitor. Deposition of this unique, pathological form of HA (HC-HA) leads to the formation of cable-like structures that promote adhesion of leukocytes. Naive mononuclear leukocytes bind specifically to inflammation-associated HA matrices but do not adhere to HA constitutively expressed under homeostatic conditions. In this study, we have directly investigated a role for the blood-coagulation protease thrombin in regulating the adhesion of monocytic cells to smooth muscle cells producing an inflammatory matrix. Our data demonstrate that the proteolytic activity of thrombin negatively regulates the adhesion of monocytes to an inflammatory HC-HA complex. This effect is independent of protease-activated receptor activation but requires proteolytic activity toward a novel substrate. Components of HC-HA complexes were predicted to contain conserved thrombin susceptible cleavage sites based on sequence analysis, and heavy chain 1 (HC1) was confirmed to be a substrate of thrombin. Thrombin treatment is sufficient to cleave HC1 associated with either cell-surface HA or serum inter-alpha-trypsin inhibitor. Furthermore, thrombin treatment of the inflammatory matrix leads to dissolution of HC-HA cable structures and abolishes leukocyte adhesion. These data establish a novel mechanism whereby thrombin cleavage of HC1 regulates the adhesive properties of an inflammatory HA matrix. PMID- 27679490 TI - Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin. AB - Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO formation and concluded that this minor pathway could provide the link between vascular GTN metabolism and activation of sGC. However, lack of detectable NO at therapeutically relevant GTN concentrations (<=1 MUm) in vascular tissue called into question the biological significance of NO formation by purified ALDH2. We addressed this issue and used a novel, highly sensitive genetically encoded fluorescent NO probe (geNOp) to visualize intracellular NO formation at low GTN concentrations (<=1 MUm) in cultured vascular smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-based GTN denitration activity. NO formation was compared with GTN induced activation of sGC. The addition of 1 MUm GTN to VSMC expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation, with maximal concentrations of 7 and 17 nm, respectively. Formation of GTN derived NO correlated well with activation of purified sGC in VSMC lysates and cGMP accumulation in intact porcine aortic endothelial cells infected with wild type or mutant ALDH2. Formation of NO and cGMP accumulation were inhibited by ALDH inhibitors chloral hydrate and daidzin. The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient for GTN bioactivation in VSMC. PMID- 27679492 TI - Non-alcoholic fatty liver disease as driving force in coronary heart disease? PMID- 27679491 TI - Structures of Proline Utilization A (PutA) Reveal the Fold and Functions of the Aldehyde Dehydrogenase Superfamily Domain of Unknown Function. AB - Aldehyde dehydrogenases (ALDHs) catalyze the NAD(P)+-dependent oxidation of aldehydes to carboxylic acids and are important for metabolism and detoxification. Although the ALDH superfamily fold is well established, some ALDHs contain an uncharacterized domain of unknown function (DUF) near the C terminus of the polypeptide chain. Herein, we report the first structure of a protein containing the ALDH superfamily DUF. Proline utilization A from Sinorhizobium meliloti (SmPutA) is a 1233-residue bifunctional enzyme that contains the DUF in addition to proline dehydrogenase and l-glutamate-gamma semialdehyde dehydrogenase catalytic modules. Structures of SmPutA with a proline analog bound to the proline dehydrogenase site and NAD+ bound to the ALDH site were determined in two space groups at 1.7-1.9 A resolution. The DUF consists of a Rossmann dinucleotide-binding fold fused to a three-stranded beta-flap. The Rossmann domain resembles the classic ALDH superfamily NAD+-binding domain, whereas the flap is strikingly similar to the ALDH superfamily dimerization domain. Paradoxically, neither structural element performs its implied function. Electron density maps show that NAD+ does not bind to the DUF Rossmann fold, and small-angle X-ray scattering reveals a novel dimer that has never been seen in the ALDH superfamily. The structure suggests that the DUF is an adapter domain that stabilizes the aldehyde substrate binding loop and seals the substrate channeling tunnel via tertiary structural interactions that mimic the quaternary structural interactions found in non-DUF PutAs. Kinetic data for SmPutA indicate a substrate-channeling mechanism, in agreement with previous studies of other PutAs. PMID- 27679495 TI - Plant Resistance to the Moth Tuta absoluta (Meyrick) (Lepidoptera:Gelechiidae) in Tomato Cultivars. AB - The resistance of 11 tomato cultivars (Ps-6515, Berlina, Poolad, Petoprid-5, Zaman, Matin, Golsar, Sandokan-F1, Golshan-616, Sadeen-95 and Sadeen-21) to the tomato moth, Tuta absoluta (Meyrick) (Lepidoptera:Gelechiidae) was investigated under field conditions. A randomized complete block design was used with three replications. Data analysis indicated that there were significant differences (P < 0.05) among cultivars regarding leaflet damage, leaf damage, overall plant damage, number of mines per leaf, number of holes on the stem, and fruit. Our findings revealed that the cultivars Berlina, Golsar, Poolad, and Zaman were less suitable cultivars, suggesting that they are more resistant to the tomato moth than the other cultivars. The high density of leaf trichomes present in the cultivars Berlina, Zaman, and Golsar can be one of the possible causes of resistance to T. absoluta. Knowledge of the extent of susceptibility or resistance of cultivars to a pest on a crop is one of the fundamental components of integrated pest management (IPM) programs for any crop. PMID- 27679494 TI - 8-Aminoguanosine and 8-Aminoguanine Exert Diuretic, Natriuretic, Glucosuric, and Antihypertensive Activity. AB - In vivo, guanine moieties in DNA, RNA, guanine nucleotides, or guanosine or guanine per se can undergo nitration (for example, by peroxynitrite) or hydroxylation (for example, by superoxide anion) on position 8 of the purine ring. Subsequent catabolism of these modified biomolecules leads to the production of a diverse group of 8-nitro, 8-amino, and 8-hydroxy guanosine and guanine compounds. Indeed, studies suggest the in vivo existence of 8 nitroguanosine, 8-nitroguanine, 8-aminoguanosine, 8-aminoguanine, 8 hydroxyguanosine, 8-hydroxy-2'-deoxyguanosine, and 8-hydroxyguanine. Since a multitude of these compounds exist in vivo, and since the renal effects of 8 substituted guanosine and guanine compounds are entirely unknown, we examined the effects of guanosine, guanine, 8-nitroguanosine, 8-nitroguanine, 8 hydroxyguanosine, 8-hydroxyguanine, 8-hydroxy-2'-deoxyguanosine, 8 aminoguanosine, and 8-aminoguanine (33.5 umol/kg/min; intravenous infusion for 115 minutes) on excretion of sodium, potassium, and glucose in rats. Guanosine, 8 nitroguanosine, and 8-hydroxy-2'-deoxyguanosine had minimal natriuretic activity. Guanine, 8-nitroguanine, 8-hydroxyguanosine, and 8-hydroxyguanine had moderate natriuretic activity (increased sodium excretion by 9.4-, 7.8-, 7.1-, and 8.6 fold, respectively). In comparison with all other compounds, 8-aminoguanosine and 8-aminoguanine were highly efficacious and increased sodium excretion by 26.6- and 17.2-fold, respectively, exceeding that of a matched dose of amiloride (13.6 fold increase). 8-Aminoguanosine and 8-aminoguanine also increased glucose excretion by 12.1- and 12.2-fold, respectively, and decreased potassium excretion by 69.1 and 71.0%, respectively. Long-term radiotelemetry studies demonstrated that oral 8-aminoguanosine and 8-aminoguanine (5 mg/kg/day) suppressed deoxycorticosterone/salt-induced hypertension. These experiments demonstrate that some naturally occurring 8-substitued guanosine and guanine compounds, particularly 8-aminoguanosine and 8-aminoguanine, are potent and efficacious potassium-sparing diuretics/natriuretics that may represent a novel class of antihypertensive diuretics. PMID- 27679493 TI - MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47phox oxidative stress pathway in neutrophils. AB - OBJECTIVES: Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. DESIGNS: Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. RESULTS: Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR 223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47phox. Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47phox expression in neutrophils. Deletion of the p47phox gene ameliorated ethanol induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47phox expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. CONCLUSIONS: miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady. PMID- 27679496 TI - Dating violence, quality of life and mental health in sexual minority populations: a path analysis. AB - PURPOSE: Theories explaining the impact of intimate partner violence (IPV) on mental health have focused on heterosexual relationships. It is unclear whether mental health disparities between heterosexual and sexual minority people are due to IPV or factors related to sexual orientation. The present study aimed to investigate pathways of how sexual orientation influenced quality of life and mental health. METHODS: The present cross-sectional study was conducted in 1076 young adults in a university population (934 heterosexual and 142 sexual minority groups). Structural equation modelling was used to examine the pathways of sexual orientation, dating violence, sexual orientation concealment, quality of life and mental health (perceived stress, anxiety and depression). RESULTS: After adjusting for sociodemographic factors, quality of life in sexual minority people was poorer [estimate -2.82, 95 % confidence interval (CI) -4.77 to -0.86, p = 0.005], and stress (estimate 2.77, 95 % CI 1.64-3.92, p < 0.0001), anxiety (estimate 1.84, 95 % CI 1.13-2.56, p < 0.0001) and depression levels (estimate 0.62, 95 % CI 0.05-1.2, p < 0.0001) were higher than in heterosexual people. Dating violence and sexual orientation concealment were mediators, with the models showing a good fit. CONCLUSION: Our study has progressed investigation of the link between sexual orientation and quality of life and mental health in the Chinese context. It has helped identify health disparities between heterosexual and sexual minority people and determined specific factors affecting their quality of life and mental health. PMID- 27679497 TI - The importance of considering differential item functioning in investigating the impact of chronic conditions on health-related quality of life in a multi-ethnic Asian population. AB - PURPOSE: The present study aims to examine the impact of chronic conditions after adjusting for differential item functioning (DIF) on the various aspects of health-related quality of life (HRQoL) in a multi-ethnic Asian population in Singapore. METHOD: Data on 3006 participants from a nation-wide cross-sectional survey of mental health literacy conducted in Singapore were used. Multiple Indicators Multiple Causes model was used to investigate the effects of chronic medical conditions on various HRQoL dimensions assessed with the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) after adjusting for DIF. RESULTS: Twenty out of 36 items were detected with DIF for chronic conditions including high blood pressure, cardiovascular disorders, diabetes, cancer, neurological disorders and ulcer as well as for a few demographic factors such age, gender and marital status. Twenty significant associations between chronic conditions and SF 36 domains were observed. After controlling for all chronic conditions, socio demographic and DIF items, a significant association emerged between cardiovascular disorders and physical functioning, while the association between diabetes and ulcer and general health became nonsignificant. All other associations remained statistically significant. CONCLUSION: Our findings provide useful information and important implications of DIF on the impact of chronic conditions on HRQoL. We found the impact of DIF with respect to the impact of chronic conditions on HRQoL to be minimal after accounting for measurement bias in this multiracial Asian population. PMID- 27679499 TI - Prof. Huan-Yong Chen: a leading botanist and taxonomist, one of the pioneers and founders of modern plant taxonomy in China. PMID- 27679498 TI - In Their Own Words: Rural Adolescent Stressors and Relationship to Depressive Symptoms. AB - This study evaluated qualitative reports of stressful life events from young rural adolescents and examined the relationship between stressor themes and depressive symptoms. A phenomenological approach guided content analysis of qualitative data. Number of themes within each response was tabulated, and association with depressive symptoms was then examined. Stressors were categorized into four thematic domains: family, peers, academics, and intrapersonal. Individual themes within each domain varied, but the themes of conflict and loss were predominant in most domains. Higher number of themes were associated with elevated depressive symptoms ( p = .045). Study findings provide insight into the lived experience of adolescent stressors and provide additional empirical evidence regarding the association between stressors and depressive symptoms. The ubiquitous themes of conflict and loss, and the implications of these themes for adolescents' mental health provide insight for nurses as they advocate for quality mental and physical health care for adolescents and their families. PMID- 27679500 TI - The role of endosomal cholesterol trafficking protein, StAR-related lipid transfer domain 3 (StarD3/MLN64), in BRIN-BD11 insulinoma cells. PMID- 27679501 TI - A national survey of practical airway training in UK anaesthetic departments. Time for a national policy? AB - The Fourth National Audit Project (NAP4) recommended airway training for trainee and trained anaesthetists. As the skills required for management of airway emergencies differ from routine skills and these events are rare, practical training is likely to require training workshops. In 2013, we surveyed all UK National Health Service hospitals to examine the current practices regarding airway training workshops. We received responses from 206 hospitals (62%) covering all regions. Regarding airway workshops, 16% provide none and 51% only for trainees. Of those providing workshops, more than half are run less than annually. Workshop content varies widely, with several Difficult Airway Society (DAS) guideline techniques not taught or only infrequently. Reported barriers to training include lack of time and departmental or individual interest. Workshop based airway training is variable in provision, frequency and content, and is often not prioritised by departments or individual trainers. It could be useful if guidance on workshop organisation, frequency and content was considered nationally. PMID- 27679502 TI - Androgens modulate male-derived endothelial cell homeostasis using androgen receptor-dependent and receptor-independent mechanisms. AB - BACKGROUND: Sex-related differences in the role of androgen have been reported in cardiovascular diseases and angiogenesis. Moreover, androgen receptor (AR) has been causally involved in the homeostasis of human prostate endothelial cells. However, levels of expression, functionality and biological role of AR in male- and female-derived human endothelial cells (ECs) remain poorly characterized. The objectives of this work were (1) to characterize the functional expression of AR in male- and female-derived human umbilical vein endothelial cell (HUVEC), and (2) to specifically analyze the biological effects of DHT, and the role of AR on these effects, in male-derived HUVECs (mHUVECs). RESULTS: Immunohistochemical analyses of tissue microarrays from benign human tissues confirmed expression of AR in ECs from several androgen-regulated and non-androgen-regulated human organs. Functional expression of AR was validated in vitro in male- and female derived HUVECs using quantitative RT-PCR, immunoblotting and AR-mediated transcriptional activity assays. Our results indicated that functional expression of AR in male- and female-derived HUVECs was heterogeneous, but not sex dependent. In parallel, we analyzed in depth the biological effects of DHT, and the role of AR on these effects, on proliferation, survival and tube formation capacity in mHUVECs. Our results indicated that DHT did not affect mHUVEC survival; however, DHT stimulated mHUVEC proliferation and suppressed mHUVEC tube formation capacity. While the effect of DHT on proliferation was mediated through AR, the effect of DHT on tube formation did not depend on the presence of a functional AR, but rather depended on the ability of mHUVECs to further metabolize DHT. CONCLUSIONS: (1) Heterogeneous expression of AR in male- and female-derived HUVEC could define the presence of functionally different subpopulations of ECs that may be affected differentially by androgens, which could explain, at least in part, the pleiotropic effects of androgen on vascular biology, and (2) DHT, and metabolites of DHT, generally thought to represent progressively more hydrophilic products along the path to elimination, may have differential roles in modulating the biology of human ECs through AR-dependent and AR-independent mechanisms, respectively. PMID- 27679503 TI - Persistence with denosumab and zoledronic acid among older women: a population based cohort study. AB - : Persistence to denosumab or zoledronic acid was increased compared to oral bisphosphonates. INTRODUCTION: Denosumab and zoledronic acid are alternative therapies to oral bisphosphonates. Few studies have assessed persistence of those agents. METHODS: Incident users of denosumab and zoledronic acid were identified using healthcare databases of public drug insurance plan of Quebec province, Canada. Patients initiating therapy between October 1, 2008, and June 30, 2013, and aged 50 years and over were eligible. A persistence rate was assessed over a 2-year period. We assess the proportion of patients receiving the second, third, and fourth injections within a specific delay of predicted time of renewal of both agents. The predictors of non-persistence were analyzed using a Cox regression model only among women. RESULTS: Among 12,689 incident users, 97.2 % were women. Kaplan-Meier analysis showed a slow decline of persistence after initiating zoledronic acid compared to denosumab therapy, dropping to 81.6 and 63.3 % after 1 and 2 years of follow-up using the permissive gaps of 56 days, in contrast to zoledronic acid, where persistence rate still stays at 74.8 % after 2 years of follow-up using the permissive gap of 112 days. The likelihood of non persistence was significantly higher among new users of denosumab and zoledronic acid among older patients and year of initiation; but depression and diabetes are only predictors of non-persistence among the zoledronic group. Concomitant use of calcium and vitamin D supplements was at low level which may compromise the clinical efficacy. CONCLUSION: The persistence rate to denosumab and zoledronic acid was higher to the published data of oral bisphosphonates. The second intention of treatment seems to target more severe patients which may more likely to be compliant. PMID- 27679504 TI - A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings. AB - BACKGROUND: Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE: The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS: Pregnant women and their corresponding births during 2005-2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS: A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father. CONCLUSIONS: An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders. PMID- 27679505 TI - Erratum to: The Need for Social Ethics in Interdisciplinary Environmental Science Graduate Programs: Results from a Nation-Wide Survey in the United States. PMID- 27679506 TI - Quantifying the therapeutic requirements and potential for combination therapy to prevent bacterial coinfection during influenza. AB - Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug's efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models. The results suggest that antivirals targeting the viral life cycle are most efficacious in the first 2 days of infection, potentially because of an improved immune response, and that increasing the clearance of infected cells is important for treatment later in the infection. For a coinfection, immunotherapy could control low bacterial loads with as little as 20 % efficacy, but more effective drugs would be necessary for high bacterial loads. Antibiotics targeting bacterial replication and administered 10 h after infection would require 100 % efficacy, which could be reduced to 40 % with prophylaxis. Combining immunotherapy with antibiotics could substantially increase treatment success. Taken together, the results suggest when and why some therapies fail, determine the efficacy needed for successful treatment, identify potential immune effects, and show how the regulation of underlying mechanisms can be used to design new therapeutic strategies. PMID- 27679507 TI - Integrated RNA-seq and sRNA-seq analysis reveals miRNA effects on secondary metabolism in Solanum tuberosum L. AB - Light is a major environmental factor that affects metabolic pathways and stimulates the production of secondary metabolites in potato. However, adaptive changes in potato metabolic pathways and physiological functions triggered by light are partly explained by gene expression changes. Regulation of secondary metabolic pathways in potato has been extensively studied at transcriptional level, but little is known about the mechanisms of post-transcriptional regulation by miRNAs. To identify light-responsive miRNAs/mRNAs and construct putative metabolism pathways regulated by the miRNA-mRNA pairs, an integrated omics (sRNAome and transcriptome) analysis was performed to potato under light stimulus. A total of 31 and 48 miRNAs were identified to be differentially expressed in the leaves and tubers, respectively. Among the DEGs, 1353 genes in the leaves and 1841 genes in the tubers were upregulated, while 1595 genes in the leaves and 897 genes in the tubers were downregulated by light. Mapman enrichment analyses showed that genes related to MVA pathway, alkaloids-like, phenylpropanoids, flavonoids, and carotenoids metabolism were significantly upregulated, while genes associated with major CHO metabolism were repressed in the leaves and tubers. Integrated miRNA and mRNA profiles revealed that light responsive miRNAs are important regulators in alkaloids metabolism, UMP salvage, lipid biosynthesis, and cellulose catabolism. Moreover, several miRNAs may participate in glycoalkaloids metabolism via JA signaling pathway, UDP-glucose biosynthesis and hydroxylation reaction. This study provides a global view of miRNA and mRNA expression profiles in potato response to light, our results suggest that miRNAs might play important roles in secondary metabolic pathways, especially in glycoalkaloid biosynthesis. The findings will enlighten us on the genetic regulation of secondary metabolite pathways and pave the way for future application of genetically engineered potato. PMID- 27679508 TI - Hepatectomy for Colorectal Cancer Liver Metastases in the Era of Modern Preoperative Chemotherapy: Evaluation of Postoperative Complications. AB - BACKGROUND: Recently, an increasing number of patients with liver metastases from colorectal cancer have received chemotherapy before hepatectomy. However, the effect of chemotherapy on postoperative short-term outcome is not well defined. METHODS: We retrospectively investigated the postoperative complications of 439 patients who underwent hepatectomy for colorectal liver metastases in our division from 2005 to 2014. Patients were classified into two groups according to the presence (Cx; 84 patients) or absence (NCx; 355 patients) of preoperative chemotherapy. Univariate and multivariate analyses were conducted to determine the predictive factors for postoperative complications. RESULTS: There was neither mortality nor liver failure after surgery. There was no significant difference in the frequency of postoperative complications between Groups Cx and NCx [29 vs 26 % for all complications; both 6 % for bile leakage that required therapeutic intervention; and 2 vs 3 % for Clavien-Dindo (CD) Grade >= IIIa, respectively]. In Group Cx, morbidity rates were similar among patients with different chemotherapy regimens. Chemotherapy-related factors (administration of bevacizumab, oxaliplatin or irinotecan, duration of chemotherapy >150 days, and timing of hepatectomy) were not significantly associated with clinically relevant bile leakage and CD >= IIIa in multivariate analysis. CONCLUSION: Even after combination chemotherapy including targeted therapy, hepatectomy for colorectal liver metastases can be performed safely without increasing morbidity or mortality, if the patients fulfill the conventional criteria for surgery. PMID- 27679509 TI - Activation of the Wnt/beta-catenin pathway is common in wilms tumor, but rarely through beta-catenin mutation and APC promoter methylation. AB - PURPOSE: The Wnt/beta-catenin pathway is known to be crucial for the regulation of embryogenesis and cell differentiation, and its constitutive activation is associated with a wide range of malignancies. There are two major principles for an activated Wnt/beta-catenin pathway. The first is caused by the failure of the destruction complex, mainly due to the decreased expression of the tumor suppressor gene adenomatous polyposis coli (APC); the second is the mutation of the beta-catenin (CTNNB1) protein itself. Wilms tumors (WTs) are also thought to be malignancies with a high rate of Wnt/beta-catenin pathway activation. The aim of this study was to analyze a large cohort of WT for activated Wnt/beta-catenin pathway. METHODS: The transcription of axis inhibition protein 2 (AXIN2) and APC was analyzed by real-time PCR. Expression was compared with those in healthy renal tissues as a control. Methylation status of the APC promoter was measured by pyrosequencing and correlated with APC expression. Finally, the mutations of CTNNB1 itself were detected by Sanger sequencing. RESULTS: The analysis was done in a cohort of 103 WTs, treated in our institution. There was a significant overexpression of AXIN2 in WTs (P < 0.0001), with 33 (32 %) tumors showing higher expression (median + 3* SD) than normal kidney tissue. In contrast, the expression of APC as well as its promoter methylation did not differ from control (P = 0.78; P = 0.82). Finally, there were only seven (6.8 %) mutations detectable in CTNNB1, and five out of seven were seen in WTs with AXIN2 overexpression. CONCLUSION: The finding that AXIN2, one of the major Wnt target genes, is overexpressed in our cohort of WTs, is indicative for the activation of the Wnt/beta-catenin pathway. However, neither the alteration of APC nor frequent CTNNB1 mutations were seen in our analyses. Therefore, other mechanisms might be responsible for the common activation of the Wnt/beta-catenin pathway. PMID- 27679510 TI - What is the role of enhanced recovery after surgery in children? A scoping review. AB - PURPOSE: Enhanced recovery after surgery (ERAS) pathways are standard practice in adult specialties resulting in improved outcomes. It is unclear whether ERAS principles are applicable to Paediatric Surgery. We performed a scoping review to identify the extent to which ERAS has been used in Paediatric Surgery, the nature of interventions, and outcomes. METHODS: Pubmed, Cochrane library, Google Scholar, and Embase were searched using the terms enhanced recovery, post operative protocol/pathway, fast track surgery, and paediatric surgery. Studies were excluded if they did not include abdominal/thoracic/urological procedures in children. RESULTS: Nine studies were identified (2003-2014; total 1269 patients): three case control studies, one retrospective review and five prospective implementations, no RCTs. Interventional elements identified were post-operative feeding, mobilisation protocols, morphine-sparing analgesia, reduced use of nasogastric tubes and urinary catheters. Outcomes reported included post operative length of stay (LOS), time to oral feeding and stooling, complications, and parent satisfaction. Fast-track programmes significantly reduced LOS in 6/7 studies, time to oral feeding in 3/3 studies, and time to stooling in 2/3 studies. CONCLUSION: The use of ERAS pathways in Paediatric surgery appears very limited but such pathways may have benefits in children. Prospective studies should evaluate interventions used in adult ERAS on appropriate outcomes in the paediatric setting. PMID- 27679512 TI - Ozone levels in the Spanish Sierra de Guadarrama mountain range are above the thresholds for plant protection: analysis at 2262, 1850, and 995 m a.s.l. AB - The Sierra de Guadarrama mountain range, located at 60 km from Madrid City (Spain), includes high valuable ecosystems following an altitude gradient, some of them protected under the Sierra de Guadarrama National Park. The characteristic Mediterranean climatic conditions and the precursors emitted from Madrid favor a high photochemical production of ozone (O3) in the region. However, very little information is available about the patterns and levels of O3 and other air pollutants in the high elevation areas and their potential effects on vegetation. Ozone levels were monitored at three altitudes (2262, 1850, and 995 m a.s.l.) for at least 3 years within the 2005-2011 period. NO x and SO2 were also recorded at the highest and lowest altitude sites. Despite the inter-annual and seasonal variations detected in the O3 concentrations, the study revealed that SG is exposed to a chronic O3 pollution. The two high elevation sites showed high O3 levels even in winter and at nighttime, having low correlation with local meteorological variables. At the lower elevation site, O3 levels were more related with local meteorological and pollution conditions. Ozone concentrations at the three sites exceeded the thresholds for the protection of human health and vegetation according to the European Air Quality Directive (EU/50/2008) and the thresholds for vegetation protection of the CLRTAP. Ozone should be considered as a stress factor for the health of the Sierra de Guadarrama mountain ecosystems. Furthermore, since O3 levels at foothills differ from concentration in high elevation, monitoring stations in mountain ranges should be incorporated in regional air quality monitoring networks. PMID- 27679511 TI - Occurrence, distribution, and dechlorination of polychlorinated biphenyls and health risk assessment in Selangor River basin. AB - Polychlorinated biphenyls (PCBs) were monitored in surface water collected in the Selangor River basin, Malaysia, to identify the occurrence, distribution, and dechlorination process as well as to assess the potential adverse effects to the Malaysian population. Ten PCB homologs (i.e., mono-CBs to deca-CBs) were quantitated by using gas chromatography-mass spectrometry (GC/MS). The total concentration of PCBs in the 10 sampling sites ranged from limit of detection to 7.67 ng L-1. The higher chlorinated biphenyls (tetra-CBs to deca-CBs) were almost not detected in most of the sampling sites, whereas lower chlorinated biphenyls (mono-CBs, di-CBs, and tri-CBs) dominated more than 90 % of the 10 homologs in all the sampling sites. Therefore, the PCB load was estimated to be negligible during the sampling period because PCBs have an extremely long half-life. The PCBs, particularly higher chlorinated biphenyls, could be thoroughly dechlorinated to mono-CBs to tri-CBs by microbial decomposition in sediment or could still be accumulated in the sediment. The lower chlorinated biphenyls, however, could be resuspended or desorbed from the sediment because they have faster desorption rates and higher solubility, compared to the higher chlorinated biphenyls. The health risk for the Malaysia population by PCB intake that was estimated from the local fish consumption (7.2 ng kg-1 bw day-1) and tap water consumption (1.5 * 10-3-3.1 * 10-3 ng kg-1 bw day-1) based on the detected PCB levels in the surface water was considered to be minimal. The hazard quotient based on the tolerable daily intake (20 ng kg-1 bw day-1) was estimated at 0.36. PMID- 27679513 TI - Spectral prediction of sediment chemistry in Lake Okeechobee, Florida. AB - High-resolution diffuse reflectance spectra in the visible and near-infrared wavelengths were used to predict chemical properties of sediment samples obtained from Lake Okeechobee (FL, USA). Chemometric models yielded highly effective prediction (relative percent difference (RPD) = SD/RMSE >2) for some sediment properties including total magnesium (Mg), total calcium (Ca), total nitrogen (TN), total carbon (TC), and organic matter content (loss on ignition (LOI)). Predictions for iron (Fe), aluminum (Al), and various forms of phosphorus (total P (TP), HCl-extractable P (HCl-P), and KCl-extractable P (KCl-P)) were also sufficiently accurate (RPD > 1.5) to be considered useful; predictions for other P fractions as well as all pore water properties were poor. Notably, scanning wet sediments resulted in only a 7 % decline in RPD scores. Moreover, interpolation maps based on values predicted from wet sediment spectra captured the same spatial patterns for Ca, Mg, TC, TN, and TP as maps derived directly from wet chemistry, suggesting that field scanning of perpetually saturated sediments may be a viable option for expediting sample analysis and greatly reducing mapping costs. Indeed, the accuracy of spectral model predictions compared favorably with the accuracy of kriging model predictions derived from wet chemistry observations suggesting that, for some analytes, higher density spatial sampling enabled by use of field spectroscopy could increase the geographic accuracy of monitoring for changes in lake sediment chemical properties. PMID- 27679514 TI - A Novel Hybrid Compound LLP2A-Ale Both Prevented and Rescued the Osteoporotic Phenotype in a Mouse Model of Glucocorticoid-Induced Osteoporosis. AB - Prolonged glucocorticoid (GC) administration causes secondary osteoporosis (GIOP) and non-traumatic osteonecrosis. LLP2A-Ale is a novel bone-seeking compound that recruits mesenchymal stem cells to the bone surface, stimulates bone formation, and increases bone mass. The purpose of this study was to determine if treatment with LLP2A-Ale alone or in combination with parathyroid hormone (PTH) could prevent or treat GIOP in a mouse model. Four-month-old male Swiss-Webster mice were randomized to a prevention study with placebo, GC (day 1-28), and GC + LLP2A Ale (IV, day 1) or a treatment study with placebo, GC (days 1-56), GC + LLP2A-Ale (IV, day 28), GC + PTH, and GC + LLP2A-Ale + PTH (days 28-56). Mice were killed on day 28 (prevention study) or on day 56 (treatment study). The study endpoints included bone mass, bone strength, serum markers of bone turnover (P1NP and CTX I) and angiogenesis (VEGF-A), surface-based bone turnover, and blood vessel density. LLP2A-Ale prevented GC-induced bone loss and increased mechanical strength in the vertebral body (days 28 and 56) and femur (day 56). LLP2A-Ale, PTH, and LLP2A-Ale + PTH treatment significantly increased the mineralizing surface, bone formation rate, mineral apposition rate, double-labeled surface, and serum P1NP level on day 56. LLP2A-Ale and PTH treatment increased femoral blood vessel density and LLP2A-Ale increased serum VEGF-A on day 28. Therefore, LLP2A-Ale monotherapy could be a potential option to both prevent and treat GC induced osteoporosis and bone fragility. PMID- 27679515 TI - [Physical activity as therapeutic intervention for depression]. AB - AIM: This article gives a conspectus of the present state of research on the efficiency of exercise as a treatment for patients suffering from depression. METHODS: A systematic review of articles published between December 1980 and March 2016 was carried out. The review focused on studies that examined the effects of exercise compared to control conditions in the treatment of depression. Extracted and analyzed information from the articles included details about participants, characteristics of exercise and control conditions, assessments, study design and outcomes. RESULTS: A total of 34 of the 48 studies included in the literature search reported a significant reduction of depressive symptoms due to exercise interventions. There was a trend to reduced depressive symptoms following the exercise interventions in five studies. In nine studies no positive impact of exercise on depression and affective well-being could be detected. DISCUSSION: This review article shows that physical activity decreases depressive symptoms and increases affective well-being in patients with depressive diseases; therefore, exercise should be recommended as a component of depression treatment within the framework of a multi-dimensional approach. PMID- 27679516 TI - The Delivery of High-Dose Dry Powder Antibiotics by a Low-Cost Generic Inhaler. AB - The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer(r) that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle like particles (rifapentine). The inhalers were tested at capsule loadings of 50 mg (colistin), 30 mg (rifapentine) and 100 mg (tobramycin) using a multistage liquid impinger (MSLI) operating at 60 L/min. The device with a single pin and reduced air inlet showed a superior performance than the other prototypes in dispersing colistin and rifapentine powders, with a fine particle fraction (FPF wt% <5 MUm in the aerosol) between 62 and 68%. Subsequently, an Aerolizer(r) with the same configuration (single pin and one-third air inlet) that accommodates a size 00 capsule was designed to increase the payload of colistin and rifapentine. The performance of the device at various inspiratory flow rates and air volumes achievable by most cystic fibrosis (CF) patients was examined at the maximum capsule loading of 100 mg. The device showed optimal performance at 45 L/min with an air volume of 1.5-2.0 L for colistin and 60 L/min with an air volume of 2.0 L for rifapentine. In conclusion, the modified size 00 Aerolizer(r) inhaler as a low-cost generic device demonstrated promising results for delivery of various high-dose formulations for treatment of lung infections. PMID- 27679517 TI - Development and Translational Application of an Integrated, Mechanistic Model of Antibody-Drug Conjugate Pharmacokinetics. AB - Antibody drug conjugates (ADC), in which small molecule cytotoxic agents are non specifically linked to antibodies, can enable targeted delivery of chemotherapeutics to tumor cells. ADCs are often produced and administered as a mixture of conjugated antibodies with different drug to antibody ratios (DAR) resulting in complex and heterogeneous disposition kinetics. We developed a mechanism-based platform model that can describe and predict the complex pharmacokinetic (PK) behavior of ADCs with protease-cleavable valine-citrulline (VC) linker linked to Monomethylmonomethyl auristatin F/E by incorporating known mechanisms of ADC disposition. The model includes explicit representation of all DAR species; DAR-dependent sequential deconjugation of the drug, resulting in the conversion of higher DAR to lower DAR species; and DAR-dependent antibody/ADC clearance. PK profiles of multiple analytes (total antibody, drug-conjugated antibody, and/or antibody-conjugated drug) for different ADC molecules and targets in rodents and cynomolgus monkeys were used for model development. The integrated cross-species model was successful in capturing the multi-analyte PK profiles after administration of purified ADCs with defined DAR species and ADCs with mixtures of DAR. Human PK predictions for DSTP3086S (anti-STEAP1-vc-MMAE) with the platform model agreed well with PK (total antibody and antibody conjugated drug concentrations) measurements in the dose-ranging phase I clinical study. The integrated model is applicable to various other ADCs with different formats, conjugated drugs, and linkers, and provides a valuable tool for the exploration of mechanisms governing disposition of ADCs and enables translational predictions. PMID- 27679518 TI - Effect of Patiromer on Urinary Ion Excretion in Healthy Adults. AB - BACKGROUND AND OBJECTIVES: Patiromer is a nonabsorbed potassium-binding polymer that uses calcium as the counterexchange ion. The calcium released with potassium binding has the potential to be absorbed or bind phosphate. Because binding is not specific for potassium, patiromer can bind other cations. Here, we evaluate the effect of patiromer on urine ion excretion in healthy adults, which reflects gastrointestinal ion absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed the effect of patiromer on urine potassium, sodium, magnesium, calcium, and phosphate in two studies. Healthy adults on controlled diets in a clinical research unit were given patiromer up to 50.4 g/d divided three times a day for 8 days (dose-finding study) or 25.2 g/d in a crossover design as daily or divided (two or three times a day) doses for 18 days (dosing regimen study). On the basis of 24-hour collections, urinary ion excretion during the baseline period (days 5-11) was compared with that during the treatment period (days 13 19; dose-finding study), and the last 4 days of each period were compared across regimens (dosing regimen study). RESULTS: In the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium (P<0.01 for each). Patiromer at 25.2 g/d decreased urine potassium (mean+/ SD) by 1140+/-316 mg/d, urine magnesium by 45+/-1 mg/d, and urine sodium by 225+/ 145 mg/d. Urine calcium increased in a dose-dependent manner, and urine phosphate decreased in parallel (both P<0.01). Patiromer at 25.2 g/d increased urine calcium by 73+/-23 mg/d and decreased urine phosphate by 64+/-40 mg/d. Urine potassium, urine sodium, and urine magnesium were unaffected by dosing regimen, whereas the increase in urine calcium was significantly lower with daily compared with three times a day dosing (P=0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing (P<0.05). CONCLUSIONS: In healthy adults, patiromer reduces urine potassium, urine sodium, urine magnesium, and urine phosphate, while modestly increasing urine calcium. Compared with divided dosing, administration of patiromer once daily provides equivalent reductions in urine potassium, urine sodium, and urine magnesium, with less effect on urine calcium and urine phosphate. PMID- 27679520 TI - Patiromer-an Oral Calcium-Loaded Potassium Binder: Kalirrhea with Calciuresis. PMID- 27679519 TI - Incidence, Severity, and Outcomes of AKI Associated with Dual Renin-Angiotensin System Blockade. AB - BACKGROUND AND OBJECTIVES: The benefit of dual blockade of the renin-angiotensin system is limited by adverse effects. We performed a secondary analysis of the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) Study to describe the effect of increased intensity of renin-angiotensin system blockade on the incidence, risk factors, and outcomes of AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the VA NEPHRON-D Study, we randomized 1148 veterans receiving outpatient care with type 2 diabetes mellitus, eGFR of between 30 and 89.9 ml/min per 1.73 m2, and urinary albumin excretion of at least 300 MUg/mg creatinine (or a urinary total protein of at least 0.5 mg/mg creatinine) to either combination therapy with losartan and lisinopril or monotherapy with losartan. We identified hospitalized AKI events and their outcomes during a median follow-up of 2.2 years through systematic reporting of serious adverse events. RESULTS: The incidence of AKI was 12.2 (95% confidence interval, 10.5 to 14.0) versus 6.7 (95% confidence interval, 5.6 to 8.2) per 100 patient-years in the combination arm versus monotherapy arms (P<0.001). Individuals with AKI were more likely to develop the primary study end point of death, ESRD, or decline in kidney function (hazard ratio, 1.78; 95% confidence interval, 1.34 to 2.26; P<0.001). Patients with AKI in the combination arm had greater recovery of kidney function (75.9% versus 66.3%; P=0.04), lower 30-day mortality (4.7% versus 15.0%; P<0.01), and lower hazard for development of the primary study end point (hazard ratio, 0.60; 95% confidence interval, 0.37 to 0.98). CONCLUSIONS: Dual renin-angiotensin system blockade was associated with an increased risk of AKI compared with monotherapy, but AKI in the setting of monotherapy was associated with lower rates of recovery of kidney function, higher mortality, and higher risk of progression of kidney disease. PMID- 27679521 TI - Tool-use by rats (Rattus norvegicus): tool-choice based on tool features. AB - In the present study, we investigated whether rats (Rattus norvegicus) could be trained to use tools in an experimental setting. In Experiment 1, we investigated whether rats became able to choose appropriate hook-shaped tools to obtain food based on the spatial arrangements of the tool and food, similar to tests conducted in non-human primates and birds. With training, the rats were able to choose the appropriate hooks. In Experiments 2 and 3, we conducted transfer tests with novel tools. The rats had to choose between a functional and non-functional rake-shaped tool in these experiments. In Experiment 2, the tools differed from those of Experiment 1 in terms of shape, color, and texture. In Experiment 3, there was a contradiction between the appearance and the functionality of these tools. The rats could obtain the food with a functional rake with a transparent blade but could not obtain food with a non-functional rake with an opaque soft blade. All rats chose the functional over the non-functional rakes in Experiment 2, but none of the rats chose the functional rake in Experiment 3. Thus, the rats were able to choose the functional rakes only when there was no contradiction between the appearance and functionality of the tools. These results suggest that rats understand the spatial and physical relationships between the tool, food, and self when there was no such contradiction. PMID- 27679523 TI - Insights into Zika Virus History, Human Health Effects, and Control Measures. PMID- 27679522 TI - Setting healthcare priorities: a description and evaluation of the budgeting and planning process in county hospitals in Kenya. AB - This paper describes and evaluates the budgeting and planning processes in public hospitals in Kenya. We used a qualitative case study approach to examine these processes in two hospitals in Kenya. We collected data by in-depth interviews of national level policy makers, hospital managers, and frontline practitioners in the case study hospitals (n = 72), a review of documents, and non-participant observations within the hospitals over a 7 month period. We applied an evaluative framework that considers both consequentialist and proceduralist conditions as important to the quality of priority-setting processes. The budgeting and planning process in the case study hospitals was characterized by lack of alignment, inadequate role clarity and the use of informal priority-setting criteria. With regard to consequentialist conditions, the hospitals incorporated economic criteria by considering the affordability of alternatives, but rarely considered the equity of allocative decisions. In the first hospital, stakeholders were aware of - and somewhat satisfied with - the budgeting and planning process, while in the second hospital they were not. Decision making in both hospitals did not result in reallocation of resources. With regard to proceduralist conditions, the budgeting and planning process in the first hospital was more inclusive and transparent, with the stakeholders more empowered compared to the second hospital. In both hospitals, decisions were not based on evidence, implementation of decisions was poor and the community was not included. There were no mechanisms for appeals or to ensure that the proceduralist conditions were met in both hospitals. Public hospitals in Kenya could improve their budgeting and planning processes by harmonizing these processes, improving role clarity, using explicit priority-setting criteria, and by incorporating both consequentialist (efficiency, equity, stakeholder satisfaction and understanding, shifted priorities, implementation of decisions), and proceduralist (stakeholder engagement and empowerment, transparency, use of evidence, revisions, enforcement, and incorporating community values) conditions. PMID- 27679524 TI - Renal function predicts long-term outcome on enzyme replacement therapy in patients with Fabry disease. AB - Background: Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT). Methods: A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naive baseline on end point development despite ERT was analysed. Results: Fifty-four patients (28 females) receiving ERT (mean 81 +/- 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) <=75 mL/min/1.73 m2 in ERT naive patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex. Conclusions: In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease. PMID- 27679525 TI - Systematic Review of the Human Milk Microbiota. AB - Human milk-associated microbes are among the first to colonize the infant gut and may help to shape both short- and long-term infant health outcomes. We performed a systematic review to characterize the microbiota of human milk. Relevant primary studies were identified through a comprehensive search of PubMed (January 1, 1964, to June 31, 2015). Included studies were conducted among healthy mothers, were written in English, identified bacteria in human milk, used culture independent methods, and reported primary results at the genus level. Twelve studies satisfied inclusion criteria. All varied in geographic location and human milk collection/storage/analytic methods. Streptococcus was identified in human milk samples in 11 studies (91.6%) and Staphylococcus in 10 (83.3%); both were predominant genera in 6 (50%). Eight of the 12 studies used conventional ribosomal RNA (rRNA) polymerase chain reaction (PCR), of which 7 (87.5%) identified Streptococcus and 6 (80%) identified Staphylococcus as present. Of these 8 studies, 2 (25%) identified Streptococcus and Staphylococcus as predominant genera. Four of the 12 studies used next-generation sequencing (NGS), all of which identified Streptococcus and Staphylococcus as present and predominant genera. Relative to conventional rRNA PCR, NGS is a more sensitive method to identify/quantify bacterial genera in human milk, suggesting the predominance of Streptococcus and Staphylococcus may be underestimated in studies using older methods. These genera, Streptococcus and Staphylococcus, may be universally predominant in human milk, regardless of differences in geographic location or analytic methods. Primary studies designed to evaluate the effect of these 2 genera on short- and long-term infant outcomes are warranted. PMID- 27679527 TI - Should general practice be a specialty in its own right? PMID- 27679526 TI - Aluminum Content of Neonatal Parenteral Nutrition Solutions. AB - INTRODUCTION: Calcium chloride (CaCl2) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives. METHODS: Samples of solutions compounded with CaCl2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis. RESULTS: Solutions containing CaCl2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 +/- 23 mcg/L and 126 +/- 5 mcg/L. The Al concentration equalled 2730 +/- 20 mcg/L for the CaGlu-Gl additive and 310 +/- 80 mcg/L for the CaGlu-Pl additive. CONCLUSION: The study indicates that solutions containing CaCl2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of <=5 mcg/kg/d. PMID- 27679528 TI - Panel's "Moonshot" Goals Released. AB - The Cancer Moonshot's Blue Ribbon Panel has published 10 recommendations to help the initiative make 10 years of cancer research progress in half that time. The proposed projects include a cancer "atlas" documenting tumor evolution and a patient network to sequence tumors and recruit trial participants. PMID- 27679529 TI - A Cytosolic Amphiphilic alpha-Helix Controls the Activity of the Bile Acid sensitive Ion Channel (BASIC). AB - The bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na+ channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic alpha-helical structure within its N-terminal domain. This alpha-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction. PMID- 27679530 TI - Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome. AB - Perilipin-2 (PLIN2) is a constitutively associated cytoplasmic lipid droplet coat protein that has been implicated in fatty liver formation in non-alcoholic fatty liver disease. Mice with or without whole-body deletion of perilipin-2 (Plin2 null) were fed either Western or control diets for 30 weeks. Perilipin-2 deletion prevents obesity and insulin resistance in Western diet-fed mice and dramatically reduces hepatic triglyceride and cholesterol levels in mice fed Western or control diets. Gene and protein expression studies reveal that PLIN2 deletion suppressed SREBP-1 and SREBP-2 target genes involved in de novo lipogenesis and cholesterol biosynthetic pathways in livers of mice on either diet. GC-MS lipidomics demonstrate that this reduction correlated with profound alterations in the hepatic lipidome with significant reductions in both desaturation and elongation of hepatic neutral lipid species. To examine the possibility that lipidomic actions of PLIN2 deletion contribute to suppression of SREBP activation, we isolated endoplasmic reticulum membrane fractions from long-term Western diet-fed wild type (WT) and Plin2-null mice. Lipidomic analyses reveal that endoplasmic reticulum membranes from Plin2-null mice are markedly enriched in omega-3 and omega-6 long-chain polyunsaturated fatty acids, which others have shown inhibit SREBP activation and de novo lipogenesis. Our results identify PLIN2 as a determinant of global changes in the hepatic lipidome and suggest the hypothesis that these actions contribute to SREBP-regulated de novo lipogenesis involved in non-alcoholic fatty liver disease. PMID- 27679532 TI - Inclusion of Older People in Trials: Lessons From FAST-MAG (Field Administration of Stroke Therapy-Magnesium). PMID- 27679531 TI - Common Eye Diseases in Children in Saudi Arabia (Jazan). AB - BACKGROUND: The rise in childhood eye diseases has become a matter of concern in Saudi Arabia, and hence a study has been conducted on the residents of Jazan. The aim of the research was to find out the root cause of such issues and provide a solution to prevent such circumstances for it may affect the vision of children. In this study, therefore, we aimed to determine the types of childhood eye diseases in Jazan and to discuss the best ways to prevent them or prevent their effect on the vision of our children. Our institutions are working toward the longevity and welfare of the residents, and healthcare is one of the important aspects in such a field. METHODS: This is a retrospective review of all patients less than 18 years of age who presented to the pediatric ophthalmology clinic of Prince Mohammed Bin Nasser Hospital, Jazan, between October 2014 and October 2015. The data, collected on 385 cases, included the age at first presentation, sex, clinical diagnosis, refractive error (RE) if present, and whether the child had amblyopia. If the child did not undergo complete ophthalmic examination with cycloplegic refraction, he/she was excluded. All data were collected and analyzed using the software SPSS. A P-value < 0.05 was considered statistically significant. RESULTS: We reviewed the files of 385 children, with a male/female ratio of 1.1:1.0. The group aged 0-6 years made up the largest group (P = 0.01), and the ratio is an expression to define the credibility of the study using a chi squared test. Strabismus (36.9%), RE (26.5%), ocular trauma (7.5%), infection of cornea and conjunctiva (7.3%), and keratoconus (6.2%) were the most common conditions. There was no significant difference in presentation by age group and sex among children with REs and squint. Trauma was seen more commonly among males and in the group aged 12-18 years. CONCLUSION: In this retrospective study, the focus was on the common childhood eye diseases that were considerably high. Hypermetropia was the predominant RE, which is in contrast to other studies where myopia was more common. However, it is important to promote public education on the significance of early detection of strabismus, REs, and amblyopia and have periodic screening in schools. The discussion of the various issues is aimed at increasing the awareness and building a support for the cause by creating the knowledge base to treat things on time and acknowledging the severity of the issues. PMID- 27679533 TI - Characteristics and Outcomes of Very Elderly Enrolled in a Prehospital Stroke Research Study. AB - BACKGROUND AND PURPOSE: Greater numbers of individuals aged >=80 years enjoy a high quality of life, yet historically stroke trials have excluded this population. We aimed to describe a population of very elderly successfully enrolled into an acute stroke trial and compare their characteristics and outcomes with the younger cohort. METHODS: We analyzed consecutive patients enrolled <2 hours of symptom onset in a prehospital stroke treatment trial, the FAST-MAG clinical trial (Field Administration of Stroke Therapy-Magnesium). We gathered demographic, treatment, and outcome data for nonelderly (<80 years old), very elderly (>=80 years old), and extreme elderly (>=90 years old). We describe key differences in the population of elderly and the impact of their inclusion on the clinical trial. RESULTS: Of 1700 participants in FAST-MAG, there were 1210 nonelderly, 490 very elderly, and 60 extreme elderly subjects. Very elderly stroke patients successfully enrolled in a research study were more likely to be women, white, and have an ischemic mechanism rather than an intracerebral hemorrhage. Although the very elderly had generally poorer outcomes, 4 in 10 were functionally independent at 90 days. CONCLUSIONS: Inclusion of the very elderly population in acute stroke clinical trials would both significantly increase study participation and generalizability of future acute stroke clinical trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332. PMID- 27679535 TI - Predominant Corticospinal Tract Involvement in a Late Infant with Krabbe Disease. AB - A case of late-infantile Krabbe disease in a patient who presented with developmental regression and spastic quadriplegia in late infancy is reported. Brain magnetic resonance imaging (MRI) at 11 months of age showed predominant corticospinal tract involvement, which usually appears in adult Krabbe disease. Galactocerebrosidase activity in lymphocytes and skin fibroblasts was very low. Genetic testing revealed compound heterozygous mutations of the galactocerebrosidase (GALC) gene, c.635_646 delinsCTC and c.1901T>C [p.L618S], both of which are known pathogenic mutations. It has been reported that the c.1901T>C [p.L618S] mutation is associated with the late-onset phenotype and, in a past case, a homozygous mutation at this location showed predominant corticospinal tract involvement on MRI. Although further analysis is needed to identify the pathophysiological mechanism, this combination of mutations is likely to be associated with this unusual MRI finding in late-infantile Krabbe disease. Because these types of mutations are common for Japanese patients, it is possible that there are more undiagnosed and late-diagnosed patients of late infantile Krabbe disease who display limited lesions on MRI. Pediatricians should be aware that patients with late-infantile Krabbe disease can present with predominant corticospinal tract involvement on MRI. PMID- 27679534 TI - PET Metabolic Biomarkers for Cancer. AB - The body's main fuel sources are fats, carbohydrates (glucose), proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET) imaging using the glucose analog (18)F-fluorodeoxyglucose ((18)F-FDG) has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects. PMID- 27679536 TI - Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest. AB - BACKGROUND: We tested the hypothesis that disseminated intravascular coagulation (DIC) during the early phase of post-cardiopulmonary resuscitation (CPR) is associated with systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS) and affects the outcome of out-of-hospital cardiac arrest (OHCA) patients. METHODS: A review of the computer-based medical records of OHCA patients was retrospectively conducted and included 388 patients who were divided into DIC and non-DIC patients based on the Japanese Association for Acute Medicine DIC diagnostic criteria. DIC patients were subdivided into two groups: those with and without hyperfibrinolysis. Pre-hospital factors, platelet count, coagulation and fibrinolysis markers and lactate levels within 24 h after resuscitation were evaluated. The outcome measure was all-cause hospital mortality. RESULTS: DIC patients exhibited lower platelet counts, prolonged prothrombin time, decreased levels of fibrinogen and antithrombin associated with increased fibrinolysis than those without DIC. DIC patients more frequently developed SIRS and MODS, followed by worse outcomes than non-DIC patients. The same changes were observed in DIC patients with hyperfibrinolysis who showed a higher prevalence of MODS, leading to worse outcome than those without hyperfibrinolysis. Logistic regression analyses showed that lactate levels predicted hyperfibrinolysis and DIC is an independent predictor of patient death. Survival probabilities of DIC patients during hospital stay were significantly lower than non-DIC patients. The area under the receiver operating characteristic curve of DIC for the prediction of death was 0.704. CONCLUSIONS: The fibrinolytic phenotype of DIC during the early phase of post-CPR more frequently results in SIRS and MODS, especially in patients with hyperfibrinolysis, and affects the outcome of OHCA patients. PMID- 27679537 TI - Off-label use of the Angioseal vascular closure device for femoral arteriotomy: retrospective analysis of safety and efficacy. AB - BACKGROUND: Angioseal, an arteriotomy closure device (ACD), functions as a collagen plug that physically closes arteriotomy sites and can simultaneously induce platelet activation and aggregation. When used 'on-label', the safety and efficacy profile of Angioseal is superior compared with those of other ACDs. However, Angioseal is sometimes deployed in less than ideal situations. Therefore, we sought to assess the safety and efficacy of 'off-label' Angioseal use in patients undergoing femoral arteriotomies. METHODS: We performed a retrospective review of all femoral arterial angiograms executed at our institution between 2008 and 2014. Patients whose femoral punctures did not fit the criteria for on-label Angioseal use were included, and were dichotomized based on vascular closure (off-label Angioseal vs manual compression). RESULTS: Of the 521 patients (1023 angiograms) reviewed, 303 (58.2%) patients had off label Angioseal groin punctures. Mean patient age was 46.2+/-14.0 years, and 113 were men. 234 patients (77%) had off-label Angioseal deployment while 69 (22%) individuals received manual pressure, serving as controls. Demographic and procedural variables were nearly identical between the two groups but the Angioseal group comprised mostly patients that underwent neurointerventional procedures and thus received intraprocedural heparinization (41%) more often than the manual compression group (19%). The overall rate of major complications associated with off-label Angioseal deployment was low (<0.85%), and clinical complications were not independently associated with Angioseal use (OR 0.76 (95% CI 0.06 to 8.86); p=0.69). CONCLUSIONS: Off-label use of Angioseal was found to be safe and was not associated with an increased complication rate in our cohort. PMID- 27679538 TI - Ethical climate and missed nursing care in cancer care units. AB - BACKGROUND: Previous research has linked missed nursing care to nurses' work environment. Ethical climate is a part of work environment, but the relationship of missed care to different types of ethical climate is unknown. RESEARCH OBJECTIVES: To describe the types of ethical climate in adult in-patient cancer care settings, and their relationship to missed nursing care. RESEARCH DESIGN: A descriptive correlation design was used. Data were collected using the Ethical Climate Questionnaire and the MISSCARE survey tool, and analyzed with descriptive statistics, Pearson's correlation and analysis of variance. Participants and research context: All nurses from relevant units in the Republic of Cyprus were invited to participate. Ethical considerations: The research protocol has been approved according to national legislation, all licenses have been obtained, and respondents participated voluntarily after they have received all necessary information. FINDINGS: Response rate was 91.8%. Five types identified were as follows: caring (M = 3.18, standard deviation = 1.39); law and code (M = 3.18, standard deviation = 0.96); rules (M = 3.17, standard deviation = 0.73); instrumental (M = 2.88, standard deviation = 1.34); and independence (M = 2.74, standard deviation = 0.94). Reported overall missed care (range: 1-5) was M = 2.51 (standard deviation = 0.90), and this was positively (p < 0.05) related to instrumental (r = 0.612) and independence (r = 0.461) types and negatively (p < 0.05) related to caring (r = -0.695), rules (r = -0.367), and law and code (r = 0.487). DISCUSSION: The reported levels of missed care and the types of ethical climates present similarities and differences with the relevant literature. All types of ethical climate were related to the reported missed care. CONCLUSION: Efforts to reduce the influence of instrumental and independence types and fostering caring, law and code, and rules types might decrease missed nursing care. However, more robust evidence is needed. PMID- 27679539 TI - (18)F-fluorodeoxyglucose and (18)F-flumazenil positron emission tomography in patients with refractory epilepsy. AB - BACKGROUND: Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20-40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F FDG) as well as non routinely used (18)F-Flumazenil ((18)F-FMZ) tracers PET/CT in patients with refractory epilepsy. CONCLUSIONS: Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays (18)F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, (18)F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of (11)C FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, (18)F-FMZ might be established as one of the tracers of choice for patients with refractory epilepsy because of better sensitivity and anatomical resolution. PMID- 27679542 TI - Recurrence rate in regional lymph nodes in 737 patients with follicular or Hurthle cell neoplasms. AB - BACKGROUND: Preoperative ultrasound (US) evaluation of central and lateral neck compartments is recommended for all patients undergoing a thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. Our aim was to find out how frequent was recurrence in regional lymph nodes in patients with follicular or Hurthle cell neoplasm and usefulness of preoperative neck US investigation in patients with neoplasm. PATIENTS AND METHODS: Altogether 737 patients were surgically treated because of follicular or Hurthle cell neoplasms from 1995 to 2014 at our cancer comprehensive center, among them 207 patients (163 females, 44 males; mean age 52 years) had thyroid carcinoma. RESULTS: Carcinoma was diagnosed in follicular and Hurthle cell neoplasm in 143/428 and 64/309 of cases, respectively. A recurrence in regional lymph nodes occurred in 12/207 patients (6%) during a median follow-up of 55 months. Among patients with carcinoma a recurrence in regional lymph nodes was diagnosed in follicular and Hurthle cell neoplasms in 2% and 14%, respectively (p = 0.002). Recurrence in regional lymph nodes was diagnosed in 3/428 of all patients with follicular neoplasm and 9/309 of all patients with Hurthle cell neoplasm. CONCLUSIONS: Recurrence in lymph nodes was diagnosed in 0.7% of patients with a preoperative diagnosis of follicular neoplasm and 3% of patients with a Hurthle cell neoplasm. A recurrence in regional lymph nodes is rare in patients with carcinoma and preoperative diagnosis of follicular neoplasm. Preoperative neck ultrasound examination in patients with a follicular neoplasm is probably not useful, but in patients with Hurtle cell neoplasm it may be useful. PMID- 27679541 TI - Non-contrast computed tomography in the diagnosis of cerebral venous sinus thrombosis. AB - BACKGROUND: The aim of the study was to investigate the sensitivity and specificity of non-contrast computed tomography (NCCT) in the diagnosis of cerebral venous sinus thrombosis (CVST). Methods. Screening our neurological department database, we identified 53 patients who were admitted to neurological emergency department with clinical signs of CVST. Two independent observers assessed the NCCT scans for the presence of CVST. CT venography and/or MR venography were used as a reference standard. Interobserver agreement between the two readers was assessed using Kappa statistic. Attenuation inside the cerebral venous sinuses was measured and compared between the patient and the control group. RESULTS: CVST was confirmed in 13 patients. Sensitivity and specificity of NCCT for overall presence of CVST were 100% and 83%, respectively, with Kappa value of 0.72 (a good agreement between observers). The attenuation values between CVST patients and control group were significantly different (73.4 +/- 14.12 HU vs. 58.1 +/- 7.58 HU; p = 0.000). The ROC analysis showed an area under the curve (AUC) of 0.916 (95% CI, 0.827 - 1.00) and an optimal cutoff value of 64 HU, leading to a sensitivity of 85% and specificity of 87%. CONCLUSIONS: NCCT as a first-line investigation has a high value for diagnosis of CVST in the emergency setting. The additional measurement of the sinus attenuation may improve the diagnostic value of the examination. PMID- 27679540 TI - Uncertainties in target volume delineation in radiotherapy - are they relevant and what can we do about them? AB - BACKGROUND: Modern radiotherapy techniques enable delivery of high doses to the target volume without escalating dose to organs at risk, offering the possibility of better local control while preserving good quality of life. Uncertainties in target volume delineation have been demonstrated for most tumour sites, and various studies indicate that inconsistencies in target volume delineation may be larger than errors in all other steps of the treatment planning and delivery process. The aim of this paper is to summarize the degree of delineation uncertainties for different tumour sites reported in the literature and review the effect of strategies to minimize them. CONCLUSIONS: Our review confirmed that interobserver variability in target volume contouring represents the largest uncertainty in the process for most tumour sites, potentially resulting in a systematic error in dose delivery, which could influence local control in individual patients. For most tumour sites the optimal combination of imaging modalities for target delineation still needs to be determined. Strict use of delineation guidelines and protocols is advisable both in every day clinical practice and in clinical studies to diminish interobserver variability. Continuing medical education of radiation oncologists cannot be overemphasized, intensive formal training on interpretation of sectional imaging should be included in the program for radiation oncology residents. PMID- 27679543 TI - Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitors. AB - BACKGROUND: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. MATERIALS AND METHODS: ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL 28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay. RESULTS: The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells. CONCLUSIONS: The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors. PMID- 27679544 TI - Discovery of 'click' 1,2,3-triazolium salts as potential anticancer drugs. AB - BACKGROUND: In order to increase the effectiveness of cancer treatment, new compounds with potential anticancer activities are synthesized and screened. Here we present the screening of a new class of compounds, 1-(2-picolyl)-, 4-(2 picolyl)-, 1-(2-pyridyl)-, and 4-(2-pyridyl)-3-methyl-1,2,3-triazolium salts and 'parent' 1,2,3-triazole precursors. METHODS: Cytotoxic activity of new compounds was determined by spectrophotometric MTT assay on several tumour and one normal cell line. Effect of the selected compound to bind double stranded DNA (ds DNA) was examined by testing its influence on thermal stability of calf thymus DNA while its influence on cell cycle was determined by flow cytometric analysis. Generation of reactive oxygen species (ROS) was determined by addition of specific substrate 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA). RESULTS: Parent triazoles were largely inactive, while some of the triazolium salts were highly cytotoxic for HeLa cells. Triazolium salts exhibited high cell-type dependent cytotoxicity against different tumour cells. Selected compound (4-(4-methoxyphenyl)-3-methyl-1-(2 picolyl)-1H-1,2,3-triazolium hexafluorophosphate(V) (2b) was significantly more cytotoxic against tumour cells than to normal cells, with very high therapeutic index 7.69 for large cell lung carcinoma H460 cells. Additionally, this compound was similarly cytotoxic against parent laryngeal carcinoma HEp-2 cells and their drug resistant 7T subline, suggesting the potential of this compound in treatment of drug resistant cancers. Compound 2b arrested cells in the G1 phase of the cell cycle. It did not bind ds DNA, but induced ROS in treated cells, which further triggered cell death. CONCLUSIONS: Our results suggest that the 'click' triazolium salts are worthy of further investigation as anti-cancer agents. PMID- 27679545 TI - Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma. AB - BACKGROUND: Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). METHODS: A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffin embedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. RESULTS: HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). CONCLUSIONS: GPX1 polymorphism may influence the risk for recurrent disease in HCTC. PMID- 27679546 TI - Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk. AB - BACKGROUND: Malignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability. PATIENTS AND METHODS: We performed a case-control study of polymorphisms in mitotic kinases TTK rs151658 and BUB1B rs1031963 and rs1801376 to assess their effects on gastric cancer risk. We examined the TTK abundance in gastric cancer tissues using immunoblot analysis. RESULTS: C/G genotype of rs151658 was more frequent in patients with diffuse type of gastric cancer and G/G genotype was more common in intestinal types of gastric cancers (p = 0.049). Polymorphic genotype A/A of rs1801376 was associated with higher risk for developing diffuse type of gastric cancer in female population (p = 0.007), whereas A/A frequencies were increased in male patients with subserosa tumour cell infiltration (p = 0.009). T/T genotype of rs1031963 was associated with well differentiated tumours (p = 0.035). TT+CT genotypes of rs1031963 and GG+AG genotypes of rs1801376 were significantly associated with gastric cancer risk (dominant model; OR = 2,929, 95% CI: 1.281-6.700; p = 0.017 and dominant model; OR = 0,364, 95% CI: 0.192 0.691; p = 0.003 respectively). CONCLUSIONS: Our results suggest that polymorphisms in mitotic kinases TTK and BUB1B may contribute to gastric tumorigenesis and risk of tumour development. Further investigations on large populations and populations of different ethnicity are needed to determine their clinical utility. PMID- 27679547 TI - Metastatic sebaceous cell carcinoma, review of the literature and use of electrochemotherapy as possible new treatment modality. AB - BACKGROUND: Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. MATERIAL AND METHODS: Extensive literature search was done, and the treatment options are discussed. RESULTS: Results. The literature search found several treatment modalities in use for the treatment of metastatic extraorbital sebaceous carcinoma. Electrochemotherapy was not included in the reported treatments. We used this technique for a man of 85 years old with a recurrent and locally metastatic extraorbital sebaceous carcinoma of the scalp. During the period of 8 months, two sessions of electrochemotherapy were employed, which resulted in an objective response of the tumour and good quality of life. CONCLUSIONS: Electrochemotherapy has shown to be a interesting tools for treatment of metastatic extraorbital sebaceous carcinoma when other radical options are not available or convenient. PMID- 27679548 TI - The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients. AB - BACKGROUND: Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. PATIENTS AND METHODS: NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. RESULTS: NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (<= 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. CONCLUSIONS: A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients. PMID- 27679549 TI - Pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head with venous resection. AB - BACKGROUND: Recent reports have shown that patients with vascular tumour invasion who undergo concurrent vascular resection can achieve long-term survival rates equivalent to those without vascular involvement requiring pancreaticoduodenectomy alone. There is no consensus about which patients benefit from the portal-superior mesenteric vein resection and there is no consensus about the best surgical technique of vessel reconstruction (resection with or without graft reconstruction). As published series are small the aim of this study was to evaluate our experience in pancreatectomies with en bloc vascular resection and reconstruction of vessels. METHODS: Review of database at University Clinical Centre Maribor identified 133 patients (average age 65.4 +/- 8.6 years, 69 female patients) who underwent pancreatoduodenectomy between January 2006 and August 2014. Clinical data, operative results, pathological findings and postoperative outcomes were collected prospectively and analyzed. Current literature and our experience in pancreatectomies with en bloc vascular resection and reconstruction of portal vein are reviewed. RESULTS: Twenty-two patients out of 133 (16.5%) had portal vein-superior mesenteric vein resection and portal vein reconstruction (PVR) during pancreaticoduodenectomy. In fourteen patients portal vein was reconstructed without the use of synthetic vascular graft. In these series two types of venous reconstruction were performed. When tumour involvement was limited to the superior mesenteric vein (SPV) or portal vein (PV) such that the splenic vein could be preserved, and vessels could be approximated without tension a primary end-to-end anastomosis was performed. When tumour involved the SMV-splenic vein confluence, splenic vein ligation was necessary. In the remaining eight procedures interposition graft was needed. Dacron grafts with 10 mm diameter were used. There was no infection after dacron grafting. One patient had portal vein thrombosis after surgery: it was thrombosis after primary reconstruction. There were no thromboses in patients with synthetic graft interposition. There were no significant differences in postoperative morbidity, mortality or grades of complication between groups of patients with or without a PVR. Median survival time in months was in a group with vein resection 16.13 months and in a group without vein resection 15.17 months. Five year survival in the group without vein resection was 19.5%. Comparison of survival curves showed equal hazard rates with log-rank p = 0.090. CONCLUSIONS: Survival of patients with pancreatic cancer who undergo an R0 resection with reconstruction was comparable to those who have a standard pancreaticoduodenectomy with no added mortality or morbidity. Synthetic graft appeared to be an effective and safe option as an interposition graft for portomesenteric venous reconstruction after pancreaticoduodenectomy. PMID- 27679550 TI - Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients. AB - BACKGROUND: The aim of the study was to reach a consensus on indication and application of a hydrogel spacer based on multicentre experience and give new users important information to shorten the learning curve for this innovative technique. METHODS: The interdisciplinary meeting was attended by radiation oncologists and urologists, each with experience of 23 - 138 hydrogel injections (SpaceOAR(r)) in prostate cancer patients before dose-escalated radiotherapy. User experience was discussed and questions were defined to comprise practical information relevant for successful hydrogel injection and treatment. Answers to the defined key questions were generated. Hydrogel-associated side effects were collected to estimate the percentage, treatment and prognosis of potential risks. RESULTS: The main indication for hydrogel application was dose-escalated radiotherapy for histologically confirmed low or intermediate risk prostate cancer. It was not recommended in locally advanced prostate cancer. The injection or implantation was performed under transrectal ultrasound guidance via the transperineal approach after prior hydrodissection. The rate of injection-related G2-toxicity was 2% (n = 5) in a total of 258 hydrogel applications. The most frequent complication (n = 4) was rectal wall penetration, diagnosed at different intervals after hydrogel injection and treated conservatively. CONCLUSIONS: A consensus was reached on the application of a hydrogel spacer. Current experience demonstrated feasibility, which could promote initiation of this method in more centres to reduce radiation-related gastrointestinal toxicity of dose-escalated IGRT. However, a very low rate of a potential serious adverse event could not be excluded. Therefore, the application should carefully be discussed with the patient and be balanced against potential benefits. PMID- 27679551 TI - Excellent outcomes after radiotherapy alone for malignant spinal cord compression from myeloma. AB - BACKGROUND: Uncertainty exists whether patients with spinal cord compression (SCC) from a highly radiosensitive tumor require decompressive spinal surgery in addition to radiotherapy (RT). This study addressed the question by evaluating patients receiving RT alone for SCC from myeloma. PATIENTS AND METHODS: Data of 238 patients were retrospectively analyzed for response to RT and local control of SCC. In addition, the effect of RT on motor function (improvement, no further progression, deterioration) was evaluated. Overall response was defined as improvement or no further progression of motor dysfunction. Prior to RT, patients were presented to a neurosurgeon for evaluation whether upfront decompressive surgery was indicated (e.g. vertebral fracture or unstable spine). RESULTS: In the entire cohort, the overall response rate was 97% (53% improvement plus 44% no further progression). Following RT, 88% of the patients were able to walk. Of the 69 non-ambulatory patients 44 patients (64%) regained the ability to walk. Local control rates at 1, 2 and 3 years were 93%, 82% and 82%, respectively. A trend towards better local control was observed for patients who were ambulatory before starting RT (p = 0.08) and those with a more favorable performance status (p = 0.07). CONCLUSIONS: RT alone provided excellent response rates, functional outcomes and local control in patients with SCC from myeloma. These results should be confirmed in a prospective randomized trial. PMID- 27679552 TI - The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer. AB - BACKGROUND: Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. METHODS: We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005 2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. RESULTS: Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. CONCLUSIONS: Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID- 27679554 TI - Trusts move to new contract as BMA vows to keep fighting imposition. PMID- 27679555 TI - Elevated levels of autophagy-related marker ULK1 and mitochondrion-associated autophagy inhibitor LRPPRC are associated with biochemical progression and overall survival after androgen deprivation therapy in patients with metastatic prostate cancer. AB - AIM: To evaluate the expression levels and prognostic significance of autophagy related markers, UNC-51-like kinase1 (ULK1), Beclin1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 5 (ATG5) and mitochondrion associated autophagy inhibitor, LRPPRC, in patients with metastatic prostate cancer (PCa) after androgen deprivation therapy (ADT). METHODS: Expressions of ULK1, Beclin1, LC3, ATG5 and LRPPRC were assessed by immunohistochemical examination in 198 patients with metastatic PCa who were receiving ADT (goserelin and bicalutamide). RESULTS: High expression levels of LRPPRC and ULK1were significantly associated with Gleason score, serum prostate-specific antigen (PSA) levels, PSA levels after ADT and number of metastatic sites. High expression of ULK1 in patients with concomitant high expression of LRPPRC was significantly associated with multiple metastases, shorter biochemical progression (BCP)-free survival and shorter overall survival (OS). ULK1 expression, LRPPRC expression, Gleason score, PSA levels after ADT and number of metastatic sites were independently associated with shorter BCP-free survival and OS on multivariate analysis. Furthermore, two-year BCP rate of patients with >=3 risk factors was found to be significantly higher as compared with that of patients with <=1 and 2 risk factors. Three-year OS rate in patients with >=3 risk factors was significantly lower than that of those with <=1 and 2 risk factors. CONCLUSIONS: High expression of ULK1 concomitant with high expression of LRPPRC may serve as useful markers for shorter BCP-free survival and OS in patients with metastatic PCa after ADT. PMID- 27679553 TI - Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management. AB - Crohn disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) characterized by recurrent episodes of mucosal inflammation. This chronic mucosal inflammation has several potential consequences, one of which is the occurrence of colitis-associated colorectal cancer. Over the past decade, our understanding of the epidemiology, pathophysiology, and overall approach to diagnosing and managing colitis-associated colorectal cancer has grown considerably. In the current review article, we outline these advancements and highlight areas in need of further research. Cancer Prev Res; 9(12); 887-94. (c)2016 AACR. PMID- 27679557 TI - Control of Dynamic Limb Motion Using Fatigue-Resistant Asynchronous Intrafascicular Multi-Electrode Stimulation. AB - Asynchronous intrafascicular multi-electrode stimulation (aIFMS) of small independent populations of peripheral nerve motor axons can evoke selective, fatigue-resistant muscle forces. We previously developed a real-time proportional closed-loop control method for aIFMS generation of isometric muscle force and the present work extends and adapts this closed-loop controller to the more demanding task of dynamically controlling joint position in the presence of opposing joint torque. A proportional-integral-velocity controller, with integrator anti-windup strategies, was experimentally validated as a means to evoke motion about the hind-limb ankle joint of an anesthetized feline via aIFMS stimulation of fast twitch plantar-flexor muscles. The controller was successful in evoking steps in joint position with 2.4% overshoot, 2.3-s rise time, 4.5-s settling time, and near-zero steady-state error. Controlled step responses were consistent across changes in step size, stable against external disturbances, and reliable over time. The controller was able to evoke smooth eccentric motion at joint velocities up to 8 deg./s, as well as sinusoidal trajectories with frequencies up to 0.1 Hz, with time delays less than 1.5 s. These experiments provide important insights toward creating a robust closed-loop aIFMS controller that can evoke precise fatigue-resistant motion in paralyzed individuals, despite the complexities introduced by aIFMS. PMID- 27679558 TI - Data Publications Correlate with Citation Impact. AB - Neuroscience and molecular biology have been generating large datasets over the past years that are reshaping how research is being conducted. In their wake, open data sharing has been singled out as a major challenge for the future of research. We conducted a comparative study of citations of data publications in both fields, showing that the average publication tagged with a data-related term by the NCBI MeSH (Medical Subject Headings) curators achieves a significantly larger citation impact than the average in either field. We introduce a new metric, the data article citation index (DAC-index), to identify the most prolific authors among those data-related publications. The study is fully reproducible from an executable Rmd (R Markdown) script together with all the citation datasets. We hope these results can encourage authors to more openly publish their data. PMID- 27679556 TI - Targeting Cannabinoid CB2 Receptors in the Central Nervous System. Medicinal Chemistry Approaches with Focus on Neurodegenerative Disorders. AB - Endocannabinoids activate two types of specific G-protein-coupled receptors (GPCRs), namely cannabinoid CB1 and CB2. Contrary to the psychotropic actions of agonists of CB1 receptors, and serious side effects of the selective antagonists of this receptor, drugs acting on CB2 receptors appear as promising drugs to combat CNS diseases (Parkinson's disease, Huntington's chorea, cerebellar ataxia, amyotrohic lateral sclerosis). Differential localization of CB2 receptors in neural cell types and upregulation in neuroinflammation are keys to understand the therapeutic potential in inter alia diseases that imply progressive neurodegeneration. Medicinal chemistry approaches are now engaged to develop imaging tools to map receptors in the living human brain, to develop more efficacious agonists, and to investigate the possibility to develop allosteric modulators. PMID- 27679559 TI - Enhanced GLUT4-Dependent Glucose Transport Relieves Nutrient Stress in Obese Mice Through Changes in Lipid and Amino Acid Metabolism. AB - Impaired GLUT4-dependent glucose uptake is a contributing factor in the development of whole-body insulin resistance in obese patients and obese animal models. Previously, we demonstrated that transgenic mice engineered to express the human GLUT4 gene under the control of the human GLUT4 promoter (i.e., transgenic [TG] mice) are resistant to obesity-induced insulin resistance. A likely mechanism underlying increased insulin sensitivity is increased glucose uptake in skeletal muscle. The purpose of this study was to investigate the broader metabolic consequences of enhanced glucose uptake into muscle. We observed that the expression of several nuclear and mitochondrially encoded mitochondrial enzymes was decreased in TG mice but that mitochondrial number, size, and fatty acid respiration rates were unchanged. Interestingly, both pyruvate and glutamate respiration rates were decreased in TG mice. Metabolomics analyses of skeletal muscle samples revealed that increased GLUT4 transgene expression was associated with decreased levels of some tricarboxylic acid intermediates and amino acids, whereas the levels of several glucogenic amino acids were elevated. Furthermore, fasting acyl carnitines in obese TG mice were decreased, indicating that increased GLUT4-dependent glucose flux decreases nutrient stress by altering lipid and amino acid metabolism in skeletal muscle. PMID- 27679560 TI - Growth Hormone Control of Hepatic Lipid Metabolism. AB - In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relationship between GH and IGF-1, the relative contribution of each hormone to the development of hepatic steatosis is unclear. Our goal was to dissect the mechanisms by which hepatic GH resistance leads to steatosis and overall insulin resistance, independent of IGF-1. We have generated a combined mouse model with liver-specific ablation of GHR in which we restored liver IGF-1 expression via the hepatic IGF-1 transgene. We found that liver GHR ablation leads to increases in lipid uptake, de novo lipogenesis, hyperinsulinemia, and hyperglycemia accompanied with severe insulin resistance and increased body adiposity and serum lipids. Restoration of IGF-1 improved overall insulin sensitivity and lipid profile in serum and reduced body adiposity, but was insufficient to protect against steatosis-induced hepatic inflammation or oxidative stress. We conclude that the impaired metabolism in states of GH resistance results from direct actions of GH on lipid uptake and de novo lipogenesis, whereas its actions on extrahepatic tissues are mediated by IGF-1. PMID- 27679562 TI - Stimulation from Cochlear Implant Electrodes Assists with Recovery from Asymmetric Perceptual Tilt: Evidence from the Subjective Visual Vertical Test. AB - Vestibular end organ impairment is highly prevalent in children who have sensorineural hearing loss (SNHL) rehabilitated with cochlear implants (CIs). As a result, spatial perception is likely to be impacted in this population. Of particular interest is the perception of visual vertical because it reflects a perceptual tilt in the roll axis and is sensitive to an imbalance in otolith function. The objectives of the present study were thus to identify abnormalities in perception of the vertical plane in children with SNHL and determine whether such abnormalities could be resolved with stimulation from the CI. Participants included 53 children (15.2 +/- 4.0 years of age) with SNHL and vestibular loss, confirmed with vestibular evoked myogenic potential (VEMP) testing. Testing protocol was validated in a sample of nine young adults with normal hearing (28.8 +/- 7.7 years). Perception of visual vertical was assessed using the static Subjective Visual Vertical (SVV) test performed with and without stimulation in the participants with cochleovestibular loss. Trains of electrical pulses were delivered by an electrode in the left and/or right ear. Asymmetric spatial orientation deficits were found in nearly half of the participants with CIs (24/53 [45%]). The abnormal perception in this cohort was exacerbated by visual tilts in the direction of their deficit. Electric pulse trains delivered using the CI shifted this abnormal perception towards center (i.e., normal; p = 0.007). Importantly, this benefit was realized regardless of which ear was stimulated. These results suggest a role for CI stimulation beyond the auditory system, in particular, for improving vestibular/balance function. PMID- 27679563 TI - Editor's Highlight: Negative Predictors of Carcinogenicity for Environmental Chemicals. AB - Recent international efforts have led to proposals for modified carcinogenicity testing paradigms based on data from shorter-term studies. The main goal of the current study was to evaluate the negative predictive value (NPV) of short-term toxicity indicators on carcinogenicity study outcomes and cancer classifications for chemicals previously reviewed by the U.S. Environmental Protection Agency (EPA). Pathology data were analyzed from over 900 acceptable 2-sex guideline subchronic (3-month) and carcinogenicity studies in the U.S. EPA Toxicity Reference Database. Chemical cancer classifications were obtained from annual reports of the U.S. EPA Office of Pesticide Programs. Histopathologic risk signals and evidence of hormonal perturbation in subchronic rat studies provided 56% NPV for any tumor outcome in the rat or mouse and 75% NPV for cancer classifications not requiring quantitative risk assessment (qRA). In comparison, lack of activity in a battery of 35 in vitro cytotoxicity assays from the U.S. EPA ToxCast library provided 49% NPV for any tumor outcome and 80% NPV for cancer classifications not requiring qRA. These findings support the idea that the absence of short-term bioactivity may provide useful information for prioritizing chemicals based on potential carcinogenic risk. Additional data streams are needed to further refine these models. PMID- 27679564 TI - Posterior Superior Temporal Sulcus Responses Predict Perceived Pleasantness of Skin Stroking. AB - Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress like skin stroking. We collected functional magnetic resonance imaging data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS) responses predicted healthy participant's perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment. PMID- 27679561 TI - A Case for Microtubule Vulnerability in Amyotrophic Lateral Sclerosis: Altered Dynamics During Disease. AB - Amyotrophic lateral sclerosis (ALS) is an aggressive multifactorial disease converging on a common pathology: the degeneration of motor neurons (MNs), their axons and neuromuscular synapses. This vulnerability and dysfunction of MNs highlights the dependency of these large cells on their intracellular machinery. Neuronal microtubules (MTs) are intracellular structures that facilitate a myriad of vital neuronal functions, including activity dependent axonal transport. In ALS, it is becoming increasingly apparent that MTs are likely to be a critical component of this disease. Not only are disruptions in this intracellular machinery present in the vast majority of seemingly sporadic cases, recent research has revealed that mutation to a microtubule protein, the tubulin isoform TUBA4A, is sufficient to cause a familial, albeit rare, form of disease. In both sporadic and familial disease, studies have provided evidence that microtubule mediated deficits in axonal transport are the tipping point for MN survivability. Axonal transport deficits would lead to abnormal mitochondrial recycling, decreased vesicle and mRNA transport and limited signaling of key survival factors from the neurons peripheral synapses, causing the characteristic peripheral "die back". This disruption to microtubule dependant transport in ALS has been shown to result from alterations in the phenomenon of microtubule dynamic instability: the rapid growth and shrinkage of microtubule polymers. This is accomplished primarily due to aberrant alterations to microtubule associated proteins (MAPs) that regulate microtubule stability. Indeed, the current literature would argue that microtubule stability, particularly alterations in their dynamics, may be the initial driving force behind many familial and sporadic insults in ALS. Pharmacological stabilization of the microtubule network offers an attractive therapeutic strategy in ALS; indeed it has shown promise in many neurological disorders, ALS included. However, the pathophysiological involvement of MTs and their functions is still poorly understood in ALS. Future investigations will hopefully uncover further therapeutic targets that may aid in combating this awful disease. PMID- 27679566 TI - Prolonged Effects of Acute Stress on Decision-Making under Risk: A Human Psychophysiological Study. AB - This study investigates the prolonged effects of physiological responses induced by acute stress on risk-taking in decision-making. Participants were divided into a Stress group (N = 14) and a Control group (N = 12). The Trier Social Stress Test was administered as an acute stressor, and reading was administered as a control task; thereafter, participants performed a decision-making task in which they needed to choose a sure option or a gamble option in Gain and Loss frame trials 2 h after (non-) exposure to the stressor. Increased cortisol, adrenaline, heart rate (HR), and subjective stress levels validated acute stress manipulation. Stressed participants made fewer risky choices only in the Gain domain, whereas no effect of stress was shown in the Loss domain. Deceleration of HR reflecting attention was greater for Gains compared with Losses only in the Stress group. Risk avoidance was determined by increased levels of cortisol caused by acute stress. These results suggest that processes regarding glucocorticoid might be involved in the prolonged effects of acute stress on the evaluation of risks and the monitoring of outcomes in decision-making. PMID- 27679567 TI - Effects of Facial Symmetry and Gaze Direction on Perception of Social Attributes: A Study in Experimental Art History. AB - This article explores the possibility of testing hypotheses about art production in the past by collecting data in the present. We call this enterprise "experimental art history". Why did medieval artists prefer to paint Christ with his face directed towards the beholder, while profane faces were noticeably more often painted in different degrees of profile? Is a preference for frontal faces motivated by deeper evolutionary and biological considerations? Head and gaze direction is a significant factor for detecting the intentions of others, and accurate detection of gaze direction depends on strong contrast between a dark iris and a bright sclera, a combination that is only found in humans among the primates. One uniquely human capacity is language acquisition, where the detection of shared or joint attention, for example through detection of gaze direction, contributes significantly to the ease of acquisition. The perceived face and gaze direction is also related to fundamental emotional reactions such as fear, aggression, empathy and sympathy. The fast-track modulator model presents a related fast and unconscious subcortical route that involves many central brain areas. Activity in this pathway mediates the affective valence of the stimulus. In particular, different sub-regions of the amygdala show specific activation as response to gaze direction, head orientation and the valence of facial expression. We present three experiments on the effects of face orientation and gaze direction on the judgments of social attributes. We observed that frontal faces with direct gaze were more highly associated with positive adjectives. Does this help to associate positive values to the Holy Face in a Western context? The formal result indicates that the Holy Face is perceived more positively than profiles with both direct and averted gaze. Two control studies, using a Brazilian and a Dutch database of photographs, showed a similar but weaker effect with a larger contrast between the gaze directions for profiles. Our findings indicate that many factors affect the impression of a face, and that eye contact in combination with face direction reinforce the general impression of portraits, rather than determine it. PMID- 27679565 TI - Rehabilitation of Motor Function after Stroke: A Multiple Systematic Review Focused on Techniques to Stimulate Upper Extremity Recovery. AB - Stroke is one of the leading causes for disability worldwide. Motor function deficits due to stroke affect the patients' mobility, their limitation in daily life activities, their participation in society and their odds of returning to professional activities. All of these factors contribute to a low overall quality of life. Rehabilitation training is the most effective way to reduce motor impairments in stroke patients. This multiple systematic review focuses both on standard treatment methods and on innovating rehabilitation techniques used to promote upper extremity motor function in stroke patients. A total number of 5712 publications on stroke rehabilitation was systematically reviewed for relevance and quality with regards to upper extremity motor outcome. This procedure yielded 270 publications corresponding to the inclusion criteria of the systematic review. Recent technology-based interventions in stroke rehabilitation including non-invasive brain stimulation, robot-assisted training, and virtual reality immersion are addressed. Finally, a decisional tree based on evidence from the literature and characteristics of stroke patients is proposed. At present, the stroke rehabilitation field faces the challenge to tailor evidence-based treatment strategies to the needs of the individual stroke patient. Interventions can be combined in order to achieve the maximal motor function recovery for each patient. Though the efficacy of some interventions may be under debate, motor skill learning, and some new technological approaches give promising outcome prognosis in stroke motor rehabilitation. PMID- 27679570 TI - Correction: Functional screen identifies regulators of murine hematopoietic stem cell repopulation. PMID- 27679568 TI - The Importance of Sample Size for Reproducibility of tDCS Effects. PMID- 27679569 TI - Neural Computations in a Dynamical System with Multiple Time Scales. AB - Neural systems display rich short-term dynamics at various levels, e.g., spike frequency adaptation (SFA) at the single-neuron level, and short-term facilitation (STF) and depression (STD) at the synapse level. These dynamical features typically cover a broad range of time scales and exhibit large diversity in different brain regions. It remains unclear what is the computational benefit for the brain to have such variability in short-term dynamics. In this study, we propose that the brain can exploit such dynamical features to implement multiple seemingly contradictory computations in a single neural circuit. To demonstrate this idea, we use continuous attractor neural network (CANN) as a working model and include STF, SFA and STD with increasing time constants in its dynamics. Three computational tasks are considered, which are persistent activity, adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, and hence cannot be implemented by a single dynamical feature or any combination with similar time constants. However, with properly coordinated STF, SFA and STD, we show that the network is able to implement the three computational tasks concurrently. We hope this study will shed light on the understanding of how the brain orchestrates its rich dynamics at various levels to realize diverse cognitive functions. PMID- 27679571 TI - Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease. AB - BACKGROUND: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative diseases affect men and women brains. OBJECTIVE: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortices to analyze the possible gender influence during normal aging and in Alzheimer's disease (AD). METHODS: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak's stages of AD, were studied. Neuronal density was quantified using the optical dissector. RESULTS: Our results showed the absence of a significant neuronal loss during aging in non pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak's stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women. CONCLUSION: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration suggesting the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data. PMID- 27679573 TI - ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice. AB - We found previously that acute phase protein orosomucoid reacts to fatigue and activates C-C chemokine receptor type 5 to increase muscle glycogen storage and enhance muscle endurance (Lei et al., 2016). To explore the underlying molecular mechanisms, we investigated the role of AMP-activated protein kinase, a critical fuel sensor in skeletal muscle, in C-C chemokine receptor type 5-mediated orosomucoid action. It was found orosomucoid increased skeletal muscle AMP activated protein kinase activation in a time- and dose- dependent manner, which was largely prevented by pharmacological blocking or knockout of C-C chemokine receptor type 5. Administration of orosomucoid also significantly increased the de-phosphorylation and activity of muscle glycogen synthase, the rate-limiting enzyme for glycogen synthesis. The effect was largely absent in mice deficient in C-C chemokine receptor type 5(-/-) or AMP-activated protein kinase alpha2(-/-), the predominant isoform in skeletal muscle. Moreover, deletion of AMP-activated protein kinase alpha2 abolished the effect of orosomucoid on fatigue and muscle glycogen. These findings indicate that orosomucoid may promote glycogen storage and enhance muscle function through C-C chemokine receptor type 5-mdiated activation of AMP-activated protein kinase, which in turn activates glycogen synthase and increases muscle glycogen. PMID- 27679572 TI - Whole-Brain Atrophy Differences between Progressive Supranuclear Palsy and Idiopathic Parkinson's Disease. AB - BACKGROUND: The absence of markers for ante-mortem diagnosis of progressive supranuclear palsy (PSP), results in this disorder being commonly mistaken for other conditions, such as idiopathic Parkinson's disease (IPD). Such mistakes occur particularly in the initial stages, when "plus syndrome" has not yet clinically emerged. OBJECTIVE: To investigate the global brain volume and tissue loss in patients with PSP relative to patients with IPD and healthy controls and correlations between clinical parameters and magnetic resonance imaging (MRI) derived brain volume estimates. METHODS: T1-weighted images were obtained from three groups of Chilean Latin American adults: 21 patients with IPD, 18 patients with PSP and 14 healthy controls. We used Structural Imaging Evaluation with Normalization of Atrophy (SIENAX) to assess white matter, gray matter and whole brain volumes (normalized to cranial volume). Imaging data were used to analyze putative correlations with the clinical status of PSP and IPD patients using the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), Hoehn and Yahr (H&Y), the Clinical Global Impression for Disease Severity Scale (CGI-S) and the Frontal Assessment Battery (FAB). RESULTS: PSP patients had significantly lower whole brain volume than both IPD patients and controls. Whole brain volume reduction in PSP patients was primarily attributable to gray matter volume reduction. We found a significant correlation between brain volume reduction and clinical status in the PSP group. CONCLUSIONS: At the group level, the whole brain and gray matter volumes differentiated patients with PSP from patients with IPD. There was also significant clinical-imaging correlations with motor disturbances in PSP. PMID- 27679574 TI - In vitro Antiviral Activity of Rubia cordifolia Aerial Part Extract against Rotavirus. AB - The root of Rubia cordifolia has been used traditionally as a hemostatic agent, while the aerial part of the plant consisting of leaf and stem is known to exhibit anti-diarrheal properties and has been widely used as a remedy in many parts of China. As rotavirus is one of the most commonly associated diarrhea causing pathogen, this study aims to investigate the anti-rotaviral effect of R. cordifolia aerial part (RCAP). The cytotoxicity of RCAP toward MA-104 cells was evaluated using the WST-8 assay. Colloidal gold method and real time polymerase chain reaction (qPCR) assay were used to confirm the findings of the antiviral assay. Then, 4',6-diamidino-2-phenylindole (DAPI) staining method was subsequently used to investigate the mode of death among the cells. And the representative components of aqueous extract were isolated and identified. It was shown that both the viability of MA-104 cells and the viral load were reduced with increasing concentration of the extract. DAPI staining showed that virus induced apoptosis was the cause of the low cell viability and viral load, an effect which was accelerated with incubation in the aqueous herbal extract. The major compounds postulated to exhibit this activity were isolated from the aqueous herbal extract and identified to be compounds Xanthopurpurin and Vanillic Acid. This study showed that RCAP extract effectively inhibited rotavirus multiplication by promoting virus-induced apoptosis in MA-104 cells. PMID- 27679575 TI - Vam3, a Compound Derived from Vitis amurensis Rupr., Attenuated Colitis-Related Tumorigenesis by Inhibiting NF-kappaB Signaling Pathway. AB - BACKGROUND: Chronic inflammation is one of the important mediators of colitis related colon cancer (CRC). Abundant mast cells (MCs) were observed in the tumor microenvironment and mediators released upon MC activation play an important role in the process of chronic inflammation. Previously, we found that activation of intestine mucosal MCs recruited and modulated the inflammatory CD11b(+)Gr1(+) cells to promote the CRC development. In the current study we investigated the effects of Vam3, a resveratrol dimer with potent anti-inflammatory effects, on CRC development. METHODS: RBL-2H3 cells, a basophilic leukemia cell line, were pretreated with 2.5 or 5 uM Vam3 and then stimulated with dinitrophenol conjugated bovine serum albumin (DNP-BSA) plus lipopolysaccharide (LPS). The MC degranulation was determined by measuring beta-hexosaminidase release. Generation of TNF-alpha and IL-6 in RBL-2H3 cells or in peritoneal macrophages was determined by ELISA and real-time qPCR. NF-kappaB p65 and phospho-NF-kappaB p65 expression was determined by Western blotting. NF-kappaB activity in RAW264.7 cells was determined by luciferase reporter assay. CRC was induced in C57BL/6 mice by intraperitoneal injection of azoxymethane (AOM), followed by oral exposure to dextran sodium sulfate (DSS). Vam3 at 50 mg/kg, or disodium cromoglycate (DSCG, MC stabilizer) at 100 mg/kg, or vehicle were administrated to the mice 4 weeks after DSS withdrawal. Levels of TNF-alpha, IL-6, and mouse MC protease-1 were determined by ELISA. Infiltration of CD11b(+)Gr1(+) cells was determined by flow cytometry analysis. One-way ANOVA was used to compare difference between groups. RESULTS: Pretreatment with Vam3 significantly inhibited RBL-2H3 cell degranulation and inflammatory cytokine production from RBL-2H3 cells and from peritoneal macrophages. After Vam3 treatment, NF-kappaB activity in RAW264.7 cells, and expressions of phospho-NF-kappaB p65 in RBL-2H3 cells and in peritoneal macrophages were significantly down-regulated. In the AOM plus DSS-induced CRC murine model, the Vam3 and DSCG-treated mice had less tumor numbers than those treated with vehicle. Expression of phospho-NF-kappaB p65, production of inflammatory cytokines, and infiltration of MCs and CD11b(+)Gr1(+) cells were attenuated in the Vam3-treated mice. CONCLUSION: Vam3 treatment could attenuate the CRC development. This effect may be due to its inhibition on NF kappaB signaling pathway in MCs and macrophages of the inflamed intestines. PMID- 27679577 TI - Fluoxetine Ameliorates Atopic Dermatitis-Like Skin Lesions in BALB/c Mice through Reducing Psychological Stress and Inflammatory Response. AB - Atopic dermatitis (AD) is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p.) significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4) and IL-13 in the spleen, as well as serum immunoglobulin E (IgE) in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic. PMID- 27679576 TI - Nanomedicine-Mediated Therapies to Target Breast Cancer Stem Cells. AB - Accumulating evidences have suggested the existence of breast cancer stem cells (BCSCs), which possess the potential of both self-renewal and differentiation. The origin of BCSCs might have relationship to the development of normal mammary stem cells. BCSCs are believed to play a key role in the initiation, recurrence and chemo-/radiotherapy resistances of breast cancer. Therefore, elimination of BCSCs is crucial for breast cancer therapy. However, conventional chemo and radiation therapies cannot eradicate BCSCs effectively. Fortunately, nanotechnology holds great potential for specific and efficient anti-BCSCs treatment. "Smart" nanocarriers can distinguish BCSCs from the other breast cancer cells and selectively deliver therapeutic agents to the BCSCs. Emerging findings suggest that BCSCs in breast cancer could be successfully inhibited and even eradicated by functionalized nanomedicines. In this review, we focus on origin of BCSCs, strategies used to target BCSCs, and summarize the nanotechnology-based delivery systems that have been applied for eliminating BCSCs in breast cancer. PMID- 27679578 TI - Revisiting the Debate: Does Exercise Build Strong Bones in the Mature and Senescent Skeleton? AB - Traditional exercise programs seem to be less osteogenic in the mature and post mature skeleton compared to the young skeleton. This is likely because of the decline in sensitivity of bone to mechanical loading that occurs with advancing age. Another factor contributing to the apparently diminished benefit of exercise in older adults is failure of widely used measurement techniques (i.e., DXA) to identify changes in 3-dimensional bone structure, which are important determinants of bone strength. Moreover, although hormonal contributors to bone loss in the elderly are well-recognized, the influence of age-related increases in sympathetic nervous system activity, which impacts bone metabolism, is rarely considered. In this Perspective, we cite evidence from animal and human studies demonstrating anabolic effects of exercise on bone across the lifespan and we discuss theoretical considerations for designing exercise regimens to optimize bone health. We conclude with suggestions for future research that should help define the osteogenic potential of exercise in older individuals. PMID- 27679580 TI - Arabidopsis Mutant bik1 Exhibits Strong Resistance to Plasmodiophora brassicae. AB - Botrytis-induced kinase1 (BIK1), a receptor-like cytoplasmic kinase, plays an important role in resistance against pathogens and insects in Arabidopsis thaliana. However, it remains unknown whether BIK1 functions against Plasmodiophora brassicae, an obligate biotrophic protist that attacks cruciferous plants and induces gall formation on roots. Here, we investigated the potential roles of receptors FLS2, BAK1, and BIK1 in the infection of P. brassicae cruciferous plants. Wild-type plants, fls2, and bak1 mutants showed typical symptom on roots, and the galls were filled with large quantities of resting spores, while bik1 mutant plants exhibited strong resistance to P. brassicae. Compared with that of the wild-type plants, the root hair and cortical infection rate of bik1 mutant were significantly reduced by about 40-50%. A considerable portion of bik1 roots failed to form typical galls. Even if some small galls were formed, they were filled with multinucleate secondary plasmodia. The bik1 plants accumulated less reactive oxygen species (ROS) at infected roots than other mutants and wild-type plants. Exogenous salicylic acid (SA) treatment alleviated the clubroot symptoms in wild-type plants, and the expression of the SA signaling marker gene PR1 was significantly increased in bik1. Both sid2 (salicylic acid induction-deficient 2) and npr1-1 [non-expresser of PR genes that regulate systemic acquired resistance (SAR)] mutants showed increased susceptibility to P. brassicae compared with wild-type plants. These results suggest that the resistance of bik1 to P. brassicae is possibly mediated by SA inducible mechanisms. PMID- 27679579 TI - Calcium-Sensing Receptor Gene: Regulation of Expression. AB - The human calcium-sensing receptor gene (CASR) has 8 exons, and localizes to chromosome 3q. Exons 1A and 1B encode alternative 5'-untranslated regions (UTRs) that splice to exon 2 encoding the AUG initiation codon. Exons 2-7 encode the CaSR protein of 1078 amino acids. Promoter P1 has TATA and CCAAT boxes upstream of exon 1A, and promoter P2 has Sp1/3 motifs at the start site of exon 1B. Exon 1A transcripts from the P1 promoter are reduced in parathyroid tumors and colon carcinomas. Studies of colon carcinomas and neuroblastomas have emphasized the importance of epigenetic changes-promoter methylation of the GC-rich P2 promoter, histone acetylation-as well as involvement of microRNAs in bringing about CASR gene silencing and reduced CaSR expression. Functional cis-elements in the CASR promoters responsive to 1,25-dihydroxyvitamin D [1,25(OH)2D], proinflammatory cytokines, and the transcription factor glial cells missing-2 (GCM2) have been characterized. Reduced levels of CaSR and reduced responsiveness to active vitamin D in parathyroid neoplasia and colon carcinoma may blunt the "tumor suppressor" activity of the CaSR. The hypocalcemia of critically ill patients with burn injury or sepsis is associated with CASR gene upregulation by TNF-alpha and IL-1beta via kappaB elements, and by IL-6 via Stat1/3 and Sp1/3 elements in the CASR gene promoters, respectively. The CASR is transactivated by GCM2-the expression of which is essential for parathyroid gland development. Hyperactive forms of GCM2 may contribute to later parathyroid hyperactivity or tumorigenesis. The expression of the CaSR-the calciostat-is regulated physiologically and pathophysiologically at the gene level. PMID- 27679582 TI - Growing Different Lactuca Genotypes Aeroponically within a Tropical Greenhouse Cool Rootzone Temperatures Decreased Rootzone Ethylene Concentrations and Increased Shoot Growth. AB - Temperate crops cannot grow well in the tropics without rootzone cooling. As cooling increased production costs, this experiment aimed to study the growth of various Lactuca genotypes and propose possible ways of reducing these costs, without compromising productivity. A recombinant inbred line (RIL) of lettuce and its parental lines (L. serriola and L. sativa "Salinas") were grown aeroponically in a tropical greenhouse under 24 degrees C cool (C) or warm fluctuating 30-36 degrees C ambient (A) rootzone temperature (RZT). Their roots were misted with Netherlands standard nutrient solution for 1 min, at intervals of either 5 min (A5, C5) or 10 min (A10, C10) in attempting to reduce electricity consumption and production costs. Lower mortality and higher productivity were observed in all genotypes when grown in C-RZT. Higher shoot fresh weight was observed under C5 than C10, for the RIL and L. serriola. Since "Salinas" had similar shoot fresh weight at both C-RZ treatments, this may indicate it is more sensitive to RZT than water availability. Under A-RZ treatments, higher carotenoid content, with correspondingly higher nonphotochemical quenching, was observed in A10 for the RIL and "Salinas." Further, total chlorophyll content was also highest at this RZ treatment for the RIL though photochemical quenching was contrastingly the lowest. Cumulatively, productivity was compromised at A10 as the RIL seemed to prioritize photoprotection over efficiency in photosynthesis, under conditions of higher RZT and lower water availability. Generally, higher RZ ethylene concentrations accumulated in A10 and C10 than A5 and C5, respectively-probably due to spray frequency exerting a greater effect on RZ ethylene accumulation than RZT. In the C5 RZ treatment, lowest RZ ethylene concentration corresponded with highest shoot fresh weight. As such, further research on ethylene (in)sensitivity and water use efficiency could be conducted to identify Lactuca cultivars that are better suited for growth in the tropics, so as to allay production costs with reduced cooling and spray intervals. PMID- 27679581 TI - Skeletal Muscle Satellite Cells, Mitochondria, and MicroRNAs: Their Involvement in the Pathogenesis of ALS. AB - Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal motor neuron disorder. It results in progressive degeneration and death of upper and lower motor neurons, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between 2 and 5 years from the onset of symptoms. ALS manifests as either familial ALS (FALS) (~10% of cases) or sporadic ALS (SALS), (~90% of cases). Mutations in the copper/zinc (CuZn) superoxide dismutase (SOD1) gene account for ~20% of FALS cases and the mutant SOD1 mouse model has been used extensively to help understand the ALS pathology. As the precise mechanisms causing ALS are not well understood there is presently no cure. Recent evidence suggests that motor neuron degradation may involve a cell non-autonomous phenomenon involving numerous cell types within various tissues. Skeletal muscle is now considered as an important tissue involved in the pathogenesis of ALS by activating a retrograde signaling cascade that degrades motor neurons. Skeletal muscle heath and function are regulated by numerous factors including satellite cells, mitochondria and microRNAs. Studies demonstrate that in ALS these factors show various levels of dysregulation within the skeletal muscle. This review provides an overview of their dysregulation in various ALS models as well as how they may contribute individually and/or synergistically to the ALS pathogenesis. PMID- 27679584 TI - Effect of Empagliflozin on Left Ventricular Mass and Diastolic Function in Individuals With Diabetes: An Important Clue to the EMPA-REG OUTCOME Trial? PMID- 27679583 TI - Absence of Peripheral Pulses and Risk of Major Vascular Outcomes in Patients With Type 2 Diabetes. AB - OBJECTIVE: The burden of vascular diseases remains substantial in patients with type 2 diabetes, requiring identification of further risk markers. We tested the absence of dorsalis pedis and posterior tibial pulses as predictors of major macrovascular and microvascular events, death, and cognitive decline in this population. RESEARCH DESIGN AND METHODS: Data were derived from 11,120 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study. Absent peripheral pulses at baseline were defined as absence of at least one dorsalis pedis or posterior tibial pulse. RESULTS: Absent compared with present peripheral pulses (n = 2,218) were associated with increased 5-year risks for major macrovascular events (hazard ratio 1.47 [95% CI 1.28-1.69], P < 0.0001), myocardial infarction (1.45 [1.13-1.87], P = 0.003), stroke (1.57 [1.23-2.00], P = 0.0003), cardiovascular death (1.61 [1.33-1.95], P < 0.0001), heart failure (1.49 [1.21-1.84], P = 0.0002), all-cause mortality (1.48 [1.29-1.71], P < 0.0001), major microvascular events (1.17 [1.00-1.36], P = 0.04), nephropathy (1.24 [1.00-1.54], P = 0.04), end-stage renal disease or renal death (2.04 [1.12 3.70], P = 0.02), and peripheral neuropathy (1.13 [1.05-1.21], P = 0.0008) after multiple adjustment. Participants with absent dorsalis pedis or posterior tibial pulses had comparable hazard ratios. Risks increased proportionally with the number of absent peripheral pulses, with the highest risks observed in patients with three or four absent pulses. Every additional absent pulse increases the risk of all outcomes. CONCLUSIONS: Absent dorsalis pedis and/or posterior tibial pulses are independent predictors of major vascular outcomes in patients with type 2 diabetes. These simple clinical indicators should be used to improve risk stratification and treatment of these patients. PMID- 27679585 TI - Model Complexity in Diffusion Modeling: Benefits of Making the Model More Parsimonious. AB - The diffusion model (Ratcliff, 1978) takes into account the reaction time distributions of both correct and erroneous responses from binary decision tasks. This high degree of information usage allows the estimation of different parameters mapping cognitive components such as speed of information accumulation or decision bias. For three of the four main parameters (drift rate, starting point, and non-decision time) trial-to-trial variability is allowed. We investigated the influence of these variability parameters both drawing on simulation studies and on data from an empirical test-retest study using different optimization criteria and different trial numbers. Our results suggest that less complex models (fixing intertrial variabilities of the drift rate and the starting point at zero) can improve the estimation of the psychologically most interesting parameters (drift rate, threshold separation, starting point, and non-decision time). PMID- 27679586 TI - Performing at the Top of One's Musical Game. AB - The purpose of the present mixed method study was to investigate personal benefits, perceptions, and the effect of a 15-week sport psychological skills training program adapted for musicians. The program was individually tailored for six music performance students with the objective of facilitating the participants' instrumental practice and performance. The participants learnt techniques such as goal setting, attentional focus, arousal regulation, imagery, and acceptance training/self-talk. Zimmerman's (1989) cyclical model of self regulated learning was applied as a theoretical frame for the intervention. The present study's mixed-method approach (i.e., quan+ QUAL) included effect size, semi-structured interviews, a research log, and practice diaries of the participants (Creswell, 2009). Thematic analysis revealed that participants had little or no experience concerning planning and goal setting in regard to instrumental practice. Concentration, volition, and physical pain were additional issues that the participants struggled with at the time of pre-intervention. The study found that psychological skills training (with special emphasis on planning and goal setting) facilitated cyclical self-regulated learning patterns in the participants. In essence, the intervention was found to facilitate the participants' concentration, self-observation, self-efficacy, and coping in the face of failure. The appliance of practice journals facilitated the participants' self-observation, self-evaluation, and awareness of instrumental practice. Finally, the psychological skills intervention reduced participants' worry and anxiety in performance situations. An 8-month follow up interview revealed that the participants were still actively applying psychological skills. PMID- 27679587 TI - The Machine behind the Stage: A Neurobiological Approach toward Theoretical Issues of Sensory Perception. AB - The purpose of the present article is to try and give a brief, scientific perspective on several issues raised in the Philosophy of Perception literature. This perspective gives a central role to the brain mechanisms that underlie perception: a percept is something that emerges when the brain is activated in a certain way and thus all perceptual experiences (whether veridical, illusory, or hallucinatory) have a common cause behind them, namely a given brain-activation pattern. What distinguishes between different cases of perception is what has caused this activation pattern, i.e., something very separate and very different from the perceptual experience itself. It is argued that separating the perceptual event from its hypothetical content, a direct consequence of the way everyday language is structured, creates unnecessary ontological complications regarding the nature of the hypothetical 'object' of perception. A clear distinction between the physical properties of the real world on the one hand (e.g., wavelength reflectance), and the psychological properties of perceptual experiences on the other (e.g., color) is clearly made. Finally, although perception is a way of acquiring knowledge/information about the world, this acquisition should be considered as a cognitive process which is separate to and follows perception. Therefore, the latter should remain neutral with respect to the 'correctness' or 'truth' of the knowledge acquired. PMID- 27679588 TI - The Role of Executive Functions in Social Cognition among Children with Down Syndrome: Relationship Patterns. AB - Many studies show a link between social cognition, a set of cognitive and emotional abilities applied to social situations, and executive functions in typical developing children. Children with Down syndrome (DS) show deficits both in social cognition and in some subcomponents of executive functions. However this link has barely been studied in this population. The aim of this study is to investigate the links between social cognition and executive functions among children with DS. We administered a battery of social cognition and executive function tasks (six theory of mind tasks, a test of emotion comprehension, and three executive function tasks) to a group of 30 participants with DS between 4 and 12 years of age. The same tasks were administered to a chronological-age control group and to a control group with the same linguistic development level. Results showed that apart from deficits in social cognition and executive function abilities, children with DS displayed a slight improvement with increasing chronological age and language development in those abilities. Correlational analysis suggested that working memory was the only component that remained constant in the relation patterns of the three groups of participants, being the relation patterns similar among participants with DS and the language development control group. A multiple linear regression showed that working memory explained above 50% of the variability of social cognition in DS participants and in language development control group, whereas in the chronological-age control group this component only explained 31% of the variability. These findings, and specifically the link between working memory and social cognition, are discussed on the basis of their theoretical and practical implications for children with DS. We discuss the possibility to use a working memory training to improve social cognition in this population. PMID- 27679589 TI - The Limited Capacity of Sleep-Dependent Memory Consolidation. AB - Sleep supports memory consolidation. However, the conceptually important influence of the amount of items encoded in a memory test on this effect has not been investigated. In two experiments, participants (n = 101) learned lists of word-pairs varying in length (40, 160, 320 word-pairs) in the evening before a night of sleep (sleep group) or of sleep deprivation (wake group). After 36 h (including a night allowing recovery sleep) retrieval was tested. Compared with wakefulness, post-learning sleep enhanced retention for the 160 word-pair condition (p < 0.01), importantly, this effect completely vanished for the 320 word-pair condition. This result indicates a limited capacity for sleep-dependent memory consolidation, which is consistent with an active system consolidation view on sleep's role for memory, if it is complemented by processes of active forgetting and/or gist abstraction. Whereas the absolute benefit from sleep should have increased with increasing amounts of successfully encoded items, if sleep only passively protected memory from interference. Moreover, the finding that retention performance was significantly diminished for the 320 word-pair condition compared to the 160 word-pair condition in the sleep group, makes it tempting to speculate that with increasing loads of information encoded during wakefulness, sleep might favor processes of forgetting over consolidation. PMID- 27679590 TI - When Seeing Is Better than Doing: Preschoolers' Transfer of STEM Skills Using Touchscreen Games. AB - The purpose of this study was to examine the extent to which character familiarity and game interactivity moderate preschoolers' learning and transfer from digital games. The games were based on a popular television show and designed to test skills related to STEM (science, technology, engineering, mathematics): numerical cognition (quantity of different sets) and knowledge of a biological concept (growth). Preschoolers (3.0-5.5 years, N = 44) were assigned to play one game and watch a recording of an experimenter playing the other game. Learning was assessed during pre-test and post-test using screenshots from the game. Transfer was assessed using modified screenshots (near) and real-life objects (far). Familiarity was assessed by asking children to identify the television characters and program. Findings indicate that the effectiveness of the games varied by age and condition: younger children learned from the quantity game, but only when they watched (rather than played) the game. They did not transfer this information in either condition. Conversely, older children learned from the growth game regardless of whether they played or watched. However, older children only demonstrated far transfer if they watched (rather than played) the growth game. Thus, preschoolers may benefit more by watching a video than by playing a game if the game is cognitively demanding, perhaps because making decisions while playing the game increases cognitive load. Character familiarity did not predict learning, perhaps because there was little overlap between the lessons presented in the television program and game. Findings from the current study highlight the need for more research into educational games and applications designed for preschoolers in order to establish whether, how, and for whom screen media can be educationally valuable. PMID- 27679591 TI - Parenting Style Dimensions As Predictors of Adolescent Antisocial Behavior. AB - Antisocial behavior is strongly associated with academic failure in adolescence. There is a solid body of evidence that points to parenting style as one of its main predictors. The objective of this work is to elaborate a reduced, valid, and reliable version of the questionnaire by Oliva et al. (2007) to evaluate the dimensions of parenting style and to analyze its psychometric properties in a sample of Spanish adolescents. To that end, the designed questionnaire was applied to 1974 adolescents 12-18 years of age from Asturias (Spain). Regarding construct validity, the results show that the model that best represents the data is composed of six dimensions of parenting style, just as in the original scale, namely affection and communication; promotion of autonomy; behavioral control; psychological control; self-disclosure; and humor. The psychological control factor negatively correlates with the other factors, with the exception of behavioral control, with which it positively correlates. The remaining correlations among the factors in the parenting style questionnaire are positive. Regarding internal consistency, the reliability analysis for each factor supports the suitability of this six-factor model. With regard to criterion validity, as expected based on the evidence available, the six dimensions of parenting style correlate in a statistically significant manner with the three antisocial behavior measures used as criteria (off-line school aggression, antisocial behavior, and antisocial friendships). Specifically, all dimensions negatively correlate with the three variables, except for psychological control. In the latter case, the correlation is positive. The theoretical and practical implications of these results are discussed. PMID- 27679592 TI - Intuition and Insight: Two Processes That Build on Each Other or Fundamentally Differ? AB - Intuition and insight are intriguing phenomena of non-analytical mental functioning: whereas intuition denotes ideas that have been reached by sensing the solution without any explicit representation of it, insight has been understood as the sudden and unexpected apprehension of the solution by recombining the single elements of a problem. By face validity, the two processes appear similar; according to a lay perspective, it is assumed that intuition precedes insight. Yet, predominant scientific conceptualizations of intuition and insight consider the two processes to differ with regard to their (dis )continuous unfolding. That is, intuition has been understood as an experience based and gradual process, whereas insight is regarded as a genuinely discontinuous phenomenon. Unfortunately, both processes have been investigated differently and without much reference to each other. In this contribution, we therefore set out to fill this lacuna by examining the conceptualizations of the assumed underlying cognitive processes of both phenomena, and by also referring to the research traditions and paradigms of the respective field. Based on early work put forward by Bowers et al. (1990, 1995), we referred to semantic coherence tasks consisting of convergent word triads (i.e., the solution has the same meaning to all three clue words) and/or divergent word triads (i.e., the solution means something different with respect to each clue word) as an excellent kind of paradigm that may be used in the future to disentangle intuition and insight experimentally. By scrutinizing the underlying mechanisms of intuition and insight, with this theoretical contribution, we hope to launch lacking but needed experimental studies and to initiate scientific cooperation between the research fields of intuition and insight that are currently still separated from each other. PMID- 27679593 TI - Emotional Experience of Caam(2) in Teaching: Power and Interpretation of Teachers' Work. AB - The study explores the social psychological process of teachers' emotional experiences. Twenty-one secondary schoolteachers in Hong Kong were interviewed. The findings show that the teachers generally felt caam(2) (a Cantonese adjective that covers a range of meanings like gloomy, dreadful, tragic, pitiful, pathetic, and miserable) in teaching. The social psychological process of the emotional experience of caam(2) involves how teachers interpret the significance of their actual work in attaining the teaching goal of making a difference. If they interpret their work as incapable of fulfilling the goal, they will experience negative emotions in teaching. The findings also suggest that the interpretation is affected by teachers' power which is unequally distributed according to teachers' teaching experience and managerial roles. PMID- 27679594 TI - Acute myocardial infarction as first clinical presentation of infective endocarditis. PMID- 27679595 TI - The 'napkin-ring' constrictive pericarditis. PMID- 27679597 TI - Inversion of the left atrial appendage in an asymptomatic newborn without prior cardiac surgery. PMID- 27679596 TI - Utility of near-infrared spectroscopy for detection of thin-cap neoatherosclerosis. AB - Aims: Near-infrared spectroscopy (NIRS) has been employed to assess the composition of the atherosclerotic plaques in native coronary arteries. However, little is known about the detection of neoatherosclerosis by NIRS in in-stent restenosis (ISR). The aim of the study was to assess the relationship between the distribution of lipid determined by NIRS and morphology of ISR on optical coherence tomography (OCT). Methods and results: We performed both NIRS and OCT in 39 drug-eluting stents with ISR. Values of lipid-core burden index (LCBI) derived by NIRS were compared with the OCT-derived thickness of the fibrous cap covering neoatherosclerotic lesions. A total of 22 (49%) in-stent neointimas were identified as lipid rich by both NIRS and OCT. There was good agreement between OCT and NIRS in identifying lipid within in-stent neointima (kappa = 0.60, 95% CI: 0.34-0.86). OCT identified thin-cap neoatheromas (TCNA) (<65 um) in 12 stents (23%). The minimal cap thickness of in-stent neoatherosclerotic plaque measured by OCT correlated with the maxLCBI4mm (maximal LCBI per 4 mm) within the stent (r = -0.77, P< 0.01). Moreover, maxLCBI4mm was able to accurately predict TCNA with a cut-off value of >144. Conclusion: NIRS correlates with OCT identification of lipids in stented vessels and is able to predict the presence of thin fibrous cap neoatheroma. PMID- 27679598 TI - Left atrial function index predicts long-term survival in stable outpatients with systolic heart failure. AB - AIMS: Left atrial (LA) function index (LAFI) is a rhythm-independent index that combines LA emptying fraction (LAEF), adjusted LA volume (LAVi), and stroke volume. We evaluated LAFI as a predictor of long-term survival in outpatients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: For 3 years, we followed up 203 outpatients with a left ventricular ejection fraction <40%, who were clinically stable and on optimal therapy. The endpoint was all-cause death. LAFI was calculated as LAFI = ([LAEF * left ventricular outflow tract-velocity time integral]/[LAVi]), and was categorized into quartiles (9.26/16.56/31.92) and median (16.57). Incremental Cox regression models adjusted for significant confounders were used for survival analyses. The 3-year death rate was 30%. Higher quartiles had lower death rates (43.1%/45.1%/25.5%/6%, P < 0.001). The receiver operating characteristic curve for death was associated with LAFI (area under curve = 0.695, 95% CI 0.62-0.77, P < 0.001). In the direct comparison with LAVi and LAEF, LAFI (HRcox 0.93, 95% CI 0.89-0.97, P < 0.001) was the only predictor of survival. LAFI (HRcox 0.95, 95% CI 0.88-1.01, P = 0.099), LAFI quartiles (HR 0.29, 95% CI 0.125-0.672, P=0.004), and LAFI >=16.57 (HRcox 0.62, 95% CI 0.38-1.02, P=0.058) were adjusted predictors of survival. Subgroup analysis by heart rhythm (sinus vs. atrial fibrillation) showed that LAFI per unit increase and LAFI quartiles were independent predictors of death in both subgroups. CONCLUSION: LAFI determination in HFrEF stable outpatients is a predictor of long-term survival and provides increased prognostic value over a wide range of confounder risk factors. PMID- 27679599 TI - Cardiac metastasis revealed by ischaemic stroke: interest of multimodal imaging. PMID- 27679600 TI - Evaluation of coronary plaque characteristics with coronary computed tomography angiography in patients with non-obstructive coronary artery disease: a long-term follow-up study. AB - Aims: Recent studies suggested that even non-obstructive coronary artery disease (CAD) increases major cardiovascular adverse events (MACE) rate. Aim of this study was to evaluate whether coronary computed tomography angiography (CCTA) may detect specific plaque characteristics that may affect prognosis in patients with non-obstructive CAD. Methods: We enrolled 245 patients who underwent CCTA between April 2004 and April 2007 for suspected CAD and were found to have non obstructive CAD. Positive remodelling index (PRI), low-attenuation plaque (LAP), plaque burden (PB), spotty calcification (SC), and napkin-ring sign (NRS) have been evaluated for each coronary plaque detected. Acute coronary syndrome, all cause/cardiac death, and very late elective revascularization (vl-ER) were the endpoints of the study. Results: A total of 28 events were recorded (2 STEMI, 4 NSTEMI, 6 UA, 2 cardiac deaths, 4 non-cardiac death, and 10 vl-ERs) at long-term follow-up (98 +/- 20 months). When adjusted for significant clinical variables PRI > 1.4 (HR 3.31 CI 95% 1.11-9.91, P = 0.0392), LAP (HR 8.45 CI 95% 2.22-32.21, P = 0.0019), PB > 0.7 (HR 5.25 CI 95% 1.45-19.03, P = 0.0120), and NRS (HR 12.52 CI 95% 1.51-103.90, P = 0.0198) were still significantly associated with higher rate of hard cardiac events at follow-up. The Kaplan-Meyer curves confirmed lower cumulative hard cardiac events-free survival in patients presenting at least one coronary plaque with two or more high-risk characteristics when compared with patients with no lesion with more than one high-risk plaque characteristics (log rank P < 0.0001). Conclusions: High-risk plaque characteristics at CCTA (PRI > 1.4, PB > 0.7, LAP, and NRS) seem to be promising for risk stratification of patients with non-obstructive CAD. PMID- 27679601 TI - Clinical characteristics and determinants of exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction. AB - Aims: Recent studies have shown that exercise-induced pulmonary hypertension (EIPH) is not rare in patients with preserved left ventricular ejection fraction (LVEF). However, the determinants and clinical implication of EIPH in these patients are unclear. Methods and results: This study included 1383 patients who were referred for exercise echocardiography to evaluate unexplained exertional dyspnoea or chest discomfort. Pulmonary artery systolic pressure (PASP) was estimated from the maximal velocity of the tricuspid regurgitant jet added to a right atrial pressure of 10 mmHg. EIPH was defined as PASP >=50 mmHg during exercise. The EIPH group consisted of about one-third of all patients (436 patients, 31.5%). Patients with EIPH were older, more commonly male and had shorter exercise times. In resting echocardiographic findings, the patients with EIPH had worse diastolic function associated with a lower e' value (7.0 +/- 2.0 vs. 7.5 +/- 2.3 cm/s, P< 0.001), a longer deceleration time (238.9 +/- 54.9 vs. 232.8 +/- 46.0 ms, P= 0.043), and a higher E/e' ratio (10.1 +/- 2.9 vs. 9.1 +/- 2.7, P< 0.001) compared with those without EIPH. In multivariable analysis, age (P< 0.001), resting E/e' ratio (P< 0.001), and resting PASP (P< 0.001) were identified as independent determinants of EIPH. Conclusion: EIPH was documented in one-third of patients with preserved LVEF. Age, resting E/e' ratio, and resting PASP were independently associated with EIPH. Therefore, EIPH should be considered as a cause of unexplained exercise intolerance in patients with preserved LVEF. PMID- 27679602 TI - 4D flow MRI demonstrates changes in cardiovascular haemodynamics in complex congenital heart disease. PMID- 27679603 TI - HIT initiative: discussion with the seniors. PMID- 27679604 TI - Multimodality imaging of a rare case of cardiac lipomatosis. PMID- 27679605 TI - Interactions Between Diet and Exposure to Secondhand Smoke on Glycated Hemoglobin Levels Among US Children: Results From NHANES 2007-2012. AB - Introduction: Antioxidant-rich diets may lessen the adverse metabolic responses triggered by exposure to secondhand smoke (SHS), but no studies have investigated these potential interactions. Objective: To examine the interaction between diet and exposure to SHS on glycated hemoglobin (HbA1c) levels among 2551 children, ages 12-19 years, who participated in the 2007-2012 National Health and Nutrition Examination Survey (NHANES). Methods: Exposure to SHS was assessed by 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), cotinine, and self-report. Weighted linear regression models evaluated the cross-sectional association between exposure to SHS and HbA1c levels. Additive interaction was assessed by introducing product terms (with SHS) of individual nutrients (dietary fiber, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], vitamin C, and vitamin E) to separate models. Results: Over half of the children had NNAL or cotinine levels above the limit of detection (56% and 71%, respectively). The median HbA1c level was 5.2% (95% confidence interval: 5.17%, 5.23%). The interaction results suggest that the effects of exposure to SHS and certain dietary nutrients (EPA, DHA, vitamin C) on HbA1c levels may not be independent. For example, although there was only a slight difference in adjusted mean HbA1c levels across NNAL categories among children with high EPA intakes, the adjusted mean HbA1c level was 0.09% higher for high NNAL as compared to low NNAL among children with low EPA intakes. Conclusions: Further research is needed to inform public health strategies for limiting increases in HbA1c levels among children. Messages may need to focus both on reducing exposure to SHS and improving diets to obtain the maximum benefit. Implications: Our results suggest that the effects of exposure to SHS and diet on HbA1c levels may not be independent. For example, although there was little effect of exposure to SHS on HbA1c levels among children with high EPA intakes, high exposure to SHS was associated with an increase in HbA1c levels among children with low EPA intakes. Further research is necessary; however, based on these joint effects, strategies for limiting increases in HbA1c levels that focus both on reducing exposure to SHS and improving diets may achieve the largest public health benefits. PMID- 27679606 TI - Implicit Attitudes and Smoking Behavior in a Smoking Cessation Induction Trial. AB - Introduction: Although studies have suggested that implicit attitudes may predict smoking-related decisions, evidence that changes in implicit attitudes toward smoking are related to changes in smoking behavior is lacking. Using data from a trial comparing interventions to induce quit attempts among unmotivated smokers, this study examined whether changes in implicit attitudes were associated with quit attempts and cessation after controlling for explicit motivation. Methods: Daily smokers recruited from the community completed measures of implicit attitudes (Implicit Association Test) and explicit measure of motivation to smoke at baseline, mid-intervention (week 12 [W12]) and follow-up (week 26 [W26]). Quit attempts and cessation were assessed at follow-up, and cessation was biochemically verified. Results: As hypothesized, Implicit Association Test scores became more negative from baseline to W12, a change that was sustained at follow-up. Logistic regression analyses in which implicit attitudes were used to predict smoking outcomes revealed that negative changes in implicit attitudes from baseline to W12 and from baseline to W26 were significantly related to quit attempts (OR = 0.71, 95% CI [0.52, 0.97], p < .05 for both) independent of explicit motivation. Negative changes in implicit attitudes from baseline to W26 were significantly related to cessation (OR = 0.50, 95% CI [0.25, 1.00], p < .05). Conclusions: Negative changes in implicit attitudes were associated with positive changes in smoking behavior independent of explicit motivation. This result indicates that smoking cessation interventions may be enhanced by incorporating strategies to change implicit attitudes, and that changes in implicit attitudes are also potentially important intervention outcomes. Implications: Smoking cessation interventions may be improved by going beyond the current focus on explicit psychological constructs and targeting automatic cognitive processes such as implicit attitudes. The results are encouragement to examine how best to manipulate smokers' implicit attitudes as well as to determine the effect on their smoking behavior. PMID- 27679607 TI - Association Between Cigarette Smoking Prevalence and Income Level: A Systematic Review and Meta-Analysis. AB - Introduction: Previous evidence linked low socioeconomic status with higher smoking prevalence. Our objective was to assess the strength of this association in the world population, updating a previous work. Methods: Systematic review and meta-analysis of observational studies. Subgroup analyses included continents, WHO regions, country mortality levels, gender, age, risk of bias, and study publication date. Independent reviewers selected studies, assessed potential bias and extracted data. We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, AFRICAN INDEX MEDICUS, and LILACS, and other sources from 1989 to 2013 reporting direct measurements of income and current cigarette smoking. Results: We retrieved 13,583 articles and included 93 for meta-analysis. Median smoking prevalence was 17.8% (range 3-70%). Lower income was consistently associated with higher smoking prevalence (odds ratio [OR]: 1.45; 95% confidence interval [CI]: 1.35-1.56). This association was statistically significant in the subgroup analysis by WHO regions for the Americas (OR: 1.54; 95% CI: 1.42-1.68), South East Asia (OR: 1.53; 95% CI: 1.10-2.00), Europe (OR: 1.45; 95% CI: 1.29-1.63), and Western Pacific (OR: 1.32; 95% CI: 1.02-1.72), and in studies conducted during 1990s (OR: 1.42; 95% CI: 1.24-1.62) and 2000s (OR: 1.48; 95%CI: 1.30-1.64). Likewise, it was noted in low-mortality countries (OR: 1.48; 95% CI: 1.37-1.60) and for both genders. Prevalence was highest in the lowest income levels compared to the middle (OR: 1.69; 95% CI: 1.49-1.92), followed by the middle level compared to the highest (OR: 1.31; 95% CI: 1.20-1.43). Conclusions: Our results show that current cigarette smoking was significantly associated with lower income worldwide and across subgroups, suggesting a dose-response relationship. Implications: This unique updated systematic review shows a consistent inverse dose-response relationship between cigarette smoking and income level, present among most geographical areas and country characteristics. Public health measures should take into account this potential inequity and consider special efforts directed to disadvantaged populations. PMID- 27679608 TI - Screening for Obstructive Sleep Apnea in Type 2 Diabetes Patients - Questionnaires Are Not Good Enough. PMID- 27679609 TI - Distinct Bacterial Communities in Surficial Seafloor Sediments Following the 2010 Deepwater Horizon Blowout. AB - A major fraction of the petroleum hydrocarbons discharged during the 2010 Macondo oil spill became associated with and sank to the seafloor as marine snow flocs. This sedimentation pulse induced the development of distinct bacterial communities. Between May 2010 and July 2011, full-length 16S rRNA gene clone libraries demonstrated bacterial community succession in oil-polluted sediment samples near the wellhead area. Libraries from early May 2010, before the sedimentation event, served as the baseline control. Freshly deposited oil derived marine snow was collected on the surface of sediment cores in September 2010, and was characterized by abundantly detected members of the marine Roseobacter cluster within the Alphaproteobacteria. Samples collected in mid October 2010 closest to the wellhead contained members of the sulfate-reducing, anaerobic bacterial families Desulfobacteraceae and Desulfobulbaceae within the Deltaproteobacteria, suggesting that the oil-derived sedimentation pulse triggered bacterial oxygen consumption and created patchy anaerobic microniches that favored sulfate-reducing bacteria. Phylotypes of the polycyclic aromatic hydrocarbon-degrading genus Cycloclasticus, previously found both in surface oil slicks and the deep hydrocarbon plume, were also found in oil-derived marine snow flocs sedimenting on the seafloor in September 2010, and in surficial sediments collected in October and November 2010, but not in any of the control samples. Due to the relative recalcitrance and stability of polycyclic aromatic compounds, Cycloclasticus represents the most persistent microbial marker of seafloor hydrocarbon deposition that we could identify in this dataset. The bacterial imprint of the DWH oil spill had diminished in late November 2010, when the bacterial communities in oil-impacted sediment samples collected near the Macondo wellhead began to resemble their pre-spill counterparts and spatial controls. Samples collected in summer of 2011 did not show a consistent bacterial community signature, suggesting that the bacterial community was no longer shaped by the DWH fallout of oil-derived marine snow, but instead by location-specific and seasonal factors. PMID- 27679610 TI - Orf Virus 002 Protein Targets Ovine Protein S100A4 and Inhibits NF-kappaB Signaling. AB - Orf virus (ORFV), a member of Parapoxvirus, has evolved various strategies to modulate the immune responses of host cells. The ORFV-encoded protein ORFV002, a regulator factor, has been found to inhibit the acetylation of NF-kappaB-p65 by blocking phosphorylation of NF-kappaB-p65 at Ser(276) and also to disrupt the binding of NF-kappaB-p65 and p300. To explore the mechanism by which ORFV002 regulates NF-kappaB signaling, the understanding of ORFV002 potential binding partners in host cells is critical. In this study, ovine S100 calcium binding protein A4 (S100A4), prolyl endopeptidase-like (PREPL) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8) were found to interact with ORFV002 based on the yeast two-hybrid (Y2H) assay using a cDNA library derived from primary ovine fetal turbinate cells (OFTu). GST pull-down and bidirectional co immunoprecipitation assay results demonstrate that ORFV002 interacts with S100A4 directly. Following the pEGFP-ORFV002 (p002GFP) transfection, we found that cytoplasmic S100A4 translocates into the nucleus and co-localizes with ORFV002. Furthermore, the inhibitory effect of ORFV002 on NF-kappaB signaling was significantly restored by S100A4 knock-down phenotype, suggesting that ovine S100A4 participates in the ORFV002-mediated NF-kappaB signaling. These data demonstrate that ORFV002 inhibits the NF-kappaB activation through its interaction with S100A4 along with its nucleus translocation. PMID- 27679611 TI - Architecture of Class 1, 2, and 3 Integrons from Gram Negative Bacteria Recovered among Fruits and Vegetables. AB - The spread of antibiotic resistant bacteria throughout the food chain constitutes a public health concern. To understand the contribution of fresh produce in shaping antibiotic resistance bacteria and integron prevalence in the food chain, 333 antibiotic resistance Gram negative isolates were collected from organic and conventionally produced fruits (pears, apples, and strawberries) and vegetables (lettuces, tomatoes, and carrots). Although low levels of resistance have been detected, the bacterial genera identified in the assessed fresh produce are often described not only as environmental, but mostly as commensals and opportunistic pathogens. The genomic characterization of integron-harboring isolates revealed a high number of mobile genetic elements and clinically relevant antibiotic resistance genes, of which we highlight the presence of as mcr-1, qnrA1, bla GES 11, mphA, and oqxAB. The study of class 1 (n = 8), class 2 (n = 3) and class 3 (n = 1) integrons, harbored by species such as Morganella morganii, Escherichia coli, Klebsiella pneumoniae, led to the identification of different integron promoters (PcW, PcH1, PcS, and PcWTNG-10) and cassette arrays (containing drfA, aadA, cmlA, estX, sat, and bla GES). In fact, the diverse integron backbones were associated with transposable elements (e.g., Tn402, Tn7, ISCR1, Tn2 (*), IS26, IS1326, and IS3) that conferred greater mobility. This is also the first appearance of In1258, In1259, and In3-13, which should be monitored to prevent their establishment as successfully dispersed mobile resistance integrons. These results underscore the growing concern about the dissemination of acquired resistance genes by mobile elements in the food chain. PMID- 27679612 TI - Evaluation of Staphylococcus aureus Lipoproteins: Role in Nutritional Acquisition and Pathogenicity. AB - Bacterial lipoproteins (Lpp) represent a major class of membrane proteins. They are distinguished by a lipid moiety at the N-terminus by which they are anchored either in the outer leaflet of the cytoplasmic membrane or, in Gram-negative bacteria, also in the inner leaflet of the outer membrane. In Gram-positive bacteria Lpp significantly contribute to nutrient transport, Toll-like receptor 2 activation and pathogenicity. Here we examine the Lpp of Staphylococcus aureus USA300, as a prototype for a multiple antibiotic resistant and community-acquired pathogen that is rapidly spreading worldwide. The compiled Lpp were grouped according to the postulated function and dissemination of homologs in the genus Staphylococcus and beyond. Based on this evaluation we also point out Lpp as promising vaccine candidates. PMID- 27679613 TI - High Nasal Carriage Rate of Staphylococcus aureus Containing Panton-Valentine leukocidin- and EDIN-Encoding Genes in Community and Hospital Settings in Burkina Faso. AB - The objectives of the present study were to investigate the rate of S.aureus nasal carriage and molecular characteristics in hospital and community settings in Bobo Dioulasso, Burkina Faso. Nasal samples (n = 219) were collected from 116 healthy volunteers and 103 hospitalized patients in July and August 2014. Samples were first screened using CHROMagar Staph aureus chromogenic agar plates, and S. aureus strains were identified by mass spectrometry. Antibiotic susceptibility was tested using the disk diffusion method on Muller-Hinton agar. All S. aureus isolates were genotyped using DNA microarray. Overall, the rate of S. aureus nasal carriage was 32.9% (72/219) with 29% in healthy volunteers and 37% in hospital patients. Among the S. aureus isolates, only four methicillin-resistant S. aureus (MRSA) strains were identified and all in hospital patients (3.9%). The 72 S. aureus isolates from nasal samples belonged to 16 different clonal complexes, particularly to CC 152-MSSA (22 clones) and CC1-MSSA (nine clones). Two clones were significantly associated with community settings: CC1-MSSA and CC45-MSSA. The MRSA strains belonged to the ST88-MRSA-IV or the CC8-MRSA-V complex. A very high prevalence of toxinogenic strains 52.2% (36/69), containing Panton-Valentine leucocidin- and EDIN-encoding genes, was identified among the S. aureus isolates in community and hospital settings. This study provides the first characterization of S. aureus clones and their genetic characteristics in Burkina Faso. Altogether, it highlights the low prevalence of antimicrobial resistance, high diversity of methicillin-sensitive S. aureus clones and high frequency of toxinogenic S. aureus strains. PMID- 27679614 TI - New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium. AB - The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures. Fosmidomycin is now-a-days prescribed clinically, however, less absorption, shorter half-life, and toxicity at higher doses, limits its use as an anti-malarial. The potential of other enzymes of the pathway as candidate drug targets has also been determined. This review details the various drug molecules tested against these targets with special emphasis to Plasmodium. We corroborate that MEP pathway functional within the apicoplast of Plasmodium is a major drug target, especially during erythrocytic stages. However, the major bottlenecks, bioavailability and toxicity of the new molecules needs to be addressed, before considering any new molecule as a potent antimalarial. PMID- 27679616 TI - Wide Distribution of Genes for Tetrahydromethanopterin/Methanofuran-Linked C1 Transfer Reactions Argues for Their Presence in the Common Ancestor of Bacteria and Archaea. PMID- 27679617 TI - Overexpression of a Water-Forming NADH Oxidase Improves the Metabolism and Stress Tolerance of Saccharomyces cerevisiae in Aerobic Fermentation. AB - Redox homeostasis is fundamental to the maintenance of metabolism. Redox imbalance can cause oxidative stress, which affects metabolism and growth. Water forming NADH oxidase regulates the redox balance by oxidizing cytosolic NADH to NAD(+), which relieves cytosolic NADH accumulation through rapid glucose consumption in Saccharomyces cerevisiae, thus decreasing the production of the by product glycerol in industrial ethanol production. Here, we studied the effects of overexpression of a water-forming NADH oxidase from Lactococcus lactis on the stress response of S. cerevisiae in aerobic batch fermentation, and we constructed an interaction network of transcriptional regulation and metabolic networks to study the effects of and mechanisms underlying NADH oxidase regulation. The oxidase-overexpressing strain (NOX) showed increased glucose consumption, growth, and ethanol production, while glycerol production was remarkably lower. Glucose was exhausted by NOX at 26 h, while 18.92 +/- 0.94 g/L residual glucose was left in the fermentation broth of the control strain (CON) at this time point. At 29.5 h, the ethanol concentration for NOX peaked at 35.25 +/- 1.76 g/L, which was 14.37% higher than that for CON (30.82 +/- 1.54 g/L). Gene expression involved in the synthesis of thiamine, which is associated with stress responses in various organisms, was increased in NOX. The transcription factor HAP4 was significantly upregulated in NOX at the late-exponential phase, indicating a diauxic shift in response to starvation. The apoptosis-inducing factor Nuc1 was downregulated while the transcription factor Sok2, which regulates the production of the small signaling molecule ammonia, was upregulated at the late-exponential phase, benefiting young cells on the rim. Reactive oxygen species production was decreased by 10% in NOX, supporting a decrease in apoptosis. The HOG pathway was not activated, although the osmotic stress was truly higher, indicating improved osmotolerance. Thus, the NADH oxidase can regulate the metabolism during aerobic fermentation in S. cerevisiae, thereby protecting cells against several stresses. Our findings indicate its suitability for use in industrial processes. PMID- 27679615 TI - Antimicrobial Activity and Mechanism of Inhibition of Silver Nanoparticles against Extreme Halophilic Archaea. AB - Haloarchaea are salt-loving halophilic microorganisms that inhabit marine environments, sea water, salterns, and lakes. The resistance of haloarchaea to physical extremities that challenge organismic survival is ubiquitous. Metal and antibiotic resistance of haloarchaea has been on an upsurge due to the exposure of these organisms to metal sinks and drug resistance genes augmented in their natural habitats due to anthropogenic activities and environmental pollution. The efficacy of silver nanoparticles (SNPs) as a potent and broad spectrum inhibitory agent is known, however, there are no reports on the inhibitory activity of SNPs against haloarchaea. In the present study, we have investigated the antimicrobial potentials of SNPs synthesized using aqueous leaf extract of Cinnamomum tamala against antibiotic resistant haloarchaeal isolates Haloferax prahovense RR8, Haloferax lucentense RR15, Haloarcula argentinensis RR10 and Haloarcula tradensis RR13. The synthesized SNPs were characterized by UV-Vis spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, dynamic light scattering, X-ray diffraction and Fourier transform infrared spectroscopy. The SNPs demonstrated potent antimicrobial activity against the haloarchaea with a minimum inhibitory concentration of 300-400 MUg/ml. Growth kinetics of haloarchaea in the presence of SNPs was studied by employing the Baranyi mathematical model for microbial growth using the DMFit curve fitting program. The C. tamala SNPs also demonstrated cytotoxic activity against human lung adenocarcinoma epithelial cell line (A540) and human breast adenocarcinoma cell line (MCF-7). The mechanism of inhibition of haloarchaea by the SNPs was investigated. The plausible mechanism proposed is the alterations and disruption of haloarchaeal membrane permeability by turbulence, inhibition of respiratory dehydrogenases and lipid peroxidation causing cellular and DNA damage resulting in cell death. PMID- 27679619 TI - Complete Genome Sequence of Carbonic Anhydrase Producing Psychrobacter sp. SHUES1. PMID- 27679618 TI - Unveiling the Synergistic Interaction Between Liposomal Amphotericin B and Colistin. AB - Patients with multiple comorbidities are often administered simultaneously or sequentially antifungals and antibacterial agents, without full knowledge of the consequences of drug interactions. Considering the clinical relevance of liposomal amphotericin B (L-AMB), the association between L-AMB and six antibacterial agents was evaluated against four clinical isolates and one type strain of Candida spp. and two clinical isolates and one type strain of Aspergillus fumigatus. In order to evaluate such combined effects, the minimal inhibitory concentration (MIC) of L-AMB was determined in the presence of 0.5-, 1 , 2-, and 4-fold peak plasma concentrations of each of the antibacterial drugs. Since the L-AMB/colistin (CST) association was the most synergic, viability assays were performed and the physiological status induced by this association was characterized. In addition, computational molecular dynamics studies were also performed in order to clarify the molecular interaction. The maximum synergistic effect with all antibacterial agents, except CST, was reached at fourfold the usual peak plasma concentrations, resulting in 2-to 8-fold L-AMB MIC reduction for Candida and 2-to 16-fold for Aspergillus. For CST, the greatest synergism was registered at peak plasma concentration (3 mg/L), with 4-to 8-fold L-AMB MIC reduction for Candida and 16-to 32-fold for Aspergillus. L-AMB at subinhibitory concentration (0.125 mg/L) combined with CST 3 mg/L resulted in: a decrease of fungal cell viability; an increase of cell membrane permeability; an increase of cellular metabolic activity soon after 1 h of exposure, which decreased until 24 h; and an increase of ROS production up to 24 h. From the molecular dynamics studies, AMB and CST molecules shown a propensity to form a stable molecular complex in solution, conferring a recognition and binding added value for membrane intercalation. Our results demonstrate that CST interacts synergistically with L-AMB, forming a stable complex, which promotes the fungicidal activity of L-AMB at low concentration. PMID- 27679621 TI - Geographical Distribution of Methanogenic Archaea in Nine Representative Paddy Soils in China. AB - Paddy field methanogenic archaea are responsible for methane (CH4) production and contribute significantly to climate change. The information regarding the spatial variations in the abundance, the diversity and the composition of such ecologically important microbes, however, is quite limited at large scale. In this investigation, we studied the abundance, alpha diversity and geographical distribution of methanogenic archaeal communities in nine representative paddy sites, along a large latitudinal gradient in China, using pyrosequencing and real time quantitative PCR. It is found that all paddy soils harbor constant methanogenic archaeal constituents, which is dominated by family Methanocellaceae (37.3%), Methanobacteriaceae (22.1%), Methanosaetaceae (17.2%), and Methanosarcinaceae (9.8%). Methanogenic archaeal abundance is primarily influenced by soil C (R = 0.612, P = 0.001) and N (R = 0.673, P = 0.001) contents, as well as alpha diversity by soil pH (PD: R = -0.552, P = 0.006; Chao1: R = -0.615, P = 0.002). Further exploration revealed that both spatial distance (R = 0.3469, P = 0.001, partial mental test) and soil chemical variables mainly about soil C and N (R = 0.2847, P = 0.001) are the two major factors affecting methanogenic archaeal community composition distribution in paddy soils. This finding will allow us to develop a better picture of the biogeographic ranges of these ecologically important microbes and get deeper insights into their ecology. PMID- 27679622 TI - Development of a Lateral Flow Immunoassay for the Rapid Diagnosis of Invasive Candidiasis. AB - Early and accurate diagnosis of invasive candidiasis (IC) is very important. In this study, a lateral flow immunoassay (LFIA) was developed to detect antibody against Candida albicans enolase (Eno). Colloidal gold particle labeled mouse anti human IgG (1.0 mg/L) was used as the detector reagent. Recombinant enolase (rEno, 1.0 mg/L) and goat anti IgG (1.0 mg/L) were immobilized in test and control lines, respectively, of a nitrocellulose membrane, acting as the capture reagents. The LFIA was used to detect anti Eno in 38 sera from clinically proven IC patients, as well as in 50 healthy control subjects. Compared with an indirect ELISA designed as a reference test, the specificity and sensitivity of the LFIA were 98.2 and 84.8%, respectively. Excellent agreement between the results obtained by ELISA and the LFIA (kappa = 0.851) was observed in this study. In addition, the agreement between the blood culture results and LFIA test is strong (kappa = 0.658). The data presented in the study indicate that the LFIA test is a suitable tool for the serological surveillance of IC in the field or in poorly equipped laboratories. PMID- 27679620 TI - Experimental Evolution as an Underutilized Tool for Studying Beneficial Animal Microbe Interactions. AB - Microorganisms play a significant role in the evolution and functioning of the eukaryotes with which they interact. Much of our understanding of beneficial host microbe interactions stems from studying already established associations; we often infer the genotypic and environmental conditions that led to the existing host-microbe relationships. However, several outstanding questions remain, including understanding how host and microbial (internal) traits, and ecological and evolutionary (external) processes, influence the origin of beneficial host microbe associations. Experimental evolution has helped address a range of evolutionary and ecological questions across different model systems; however, it has been greatly underutilized as a tool to study beneficial host-microbe associations. In this review, we suggest ways in which experimental evolution can further our understanding of the proximate and ultimate mechanisms shaping mutualistic interactions between eukaryotic hosts and microbes. By tracking beneficial interactions under defined conditions or evolving novel associations among hosts and microbes with little prior evolutionary interaction, we can link specific genotypes to phenotypes that can be directly measured. Moreover, this approach will help address existing puzzles in beneficial symbiosis research: how symbioses evolve, how symbioses are maintained, and how both host and microbe influence their partner's evolutionary trajectories. By bridging theoretical predictions and empirical tests, experimental evolution provides us with another approach to test hypotheses regarding the evolution of beneficial host-microbe associations. PMID- 27679624 TI - Neospora caninum Activates p38 MAPK as an Evasion Mechanism against Innate Immunity. AB - Due to the high prevalence and economic impact of neosporosis, the development of safe and effective vaccines and therapies against this parasite has been a priority in the field and is crucial to limit horizontal and vertical transmission in natural hosts. Limited data is available regarding factors that regulate the immune response against this parasite and such knowledge is essential in order to understand Neospora caninum induced pathogenesis. Mitogen activated protein kinases (MAPKs) govern diverse cellular processes, including growth, differentiation, apoptosis, and immune-mediated responses. In that sense, our goal was to understand the role of MAPKs during the infection by N. caninum. We found that p38 phosphorylation was quickly triggered in macrophages stimulated by live tachyzoites and antigen extracts, while its chemical inhibition resulted in upregulation of IL-12p40 production and augmented B7/MHC expression. In vivo blockade of p38 resulted in an amplified production of cytokines, which preceded a reduction in latent parasite burden and enhanced survival against the infection. Additionally, the experiments indicate that the p38 activation is induced by a mechanism that depends on GPCR, PI3K and AKT signaling pathways, and that the phenomena here observed is distinct that those induced by Toxoplasma gondii's GRA24 protein. Altogether, these results showed that N. caninum manipulates p38 phosphorylation in its favor, in order to downregulate the host's innate immune responses. Additionally, those results infer that active interference in this signaling pathway may be useful for the development of a new therapeutic strategy against neosporosis. PMID- 27679626 TI - The infant observation task as a tool in psychiatric practice. AB - OBJECTIVE: The objective of this study was to describe the method and relevance of infant observation as a unique and powerful learning tool for psychiatrists. CONCLUSION: Infant observation provides a privileged entry into an infant's internal world to observe its earliest mental life. Weekly consecutive observations of the mother-baby dyad, combined with the process of supervision, enable identification of emergent and changing patterns in the relationship. The discipline of observation encourages attunement to the nuances of relationships, which provides a potent tool for application in other clinical settings. PMID- 27679625 TI - The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum. AB - Vibrio sp. is the most serious pathogen in marine aquaculture, and the development of anti-Vibrio agents is urgently needed. However, it is extreme lack of high-throughput screening (HTS) model for searching anti-Vibrio compounds. Here, we established a protein-based HTS screening model to identify agents targeting peptide deformylase (PDF) of Vibrio anguillarum. To find potential anti Vibrio compounds, crude extracts derived from marine actinomycetes were applied for screening with this model. Notably, crude extract of strain Streptomyces sp. NHF165 inhibited dramatically both on V. anguillarum PDF (VaPDF) activity and V. anguillarum cell growth. And actinonin was further identified as the functional component. Anti-VaPDF and anti-V. anguillarum activities of actinonin were dose dependent, and the IC50 values were 6.94 and 2.85 MUM, respectively. To understand the resistance of V. anguillarum against actinonin, spontaneous V. anguillarum mutants with resistance against actinonin were isolated. Surprisingly, for the resistant strains, the region between 774 and 852 base pairs was found to be absent in the gene folD which produces 10-formyl tetrahydrofolate, a donor of N-formyl to Met-tRNA(fmet). When compared to the wild type strain, DeltafolD mutant showed eight times of minimum inhibition concentration on actinonin, however, the folD complementary strain could not grow on the medium supplemented with actinonin, which suggested that folD gene mutation was mainly responsible for the actinonin resistance. To our knowledge, this is the first report showing that marine derived Streptomyces sp. could produce actinonin with anti-VaPDF activity and the resistance against actinonin by V. anguillarum is mediated by mutation in folD gene. PMID- 27679623 TI - New Paradigms for Virus Detection, Surveillance and Control of Zika Virus Vectors in the Settings of Southeast Asia. AB - Zika virus (ZIKV) has now become a global public health concern. The vectors for ZIKV are Aedes aegypti and A. albopictus. Both these mosquitoes are predominant in Southeast Asia and are also responsible for the spread of other arboviral diseases like dengue virus and chikungunya virus. The incidence of dengue has been increasing over the years and this is of concern to public health workers. Simple laboratory tools for the detection of ZIKV is also lacking. In the absence of drugs and vaccine for these arboviral diseases, vector control is the main option for surveillance and control. Aedes larval surveys have been the hallmark of dengue control along with larviciding and fogging when cases are reported. However, we need new paradigms and options for control of these vectors. The current situation in Southeast Asia clearly proves that effective strategies for vector control need to be proactive and not reactive. This will be the way forward to control epidemics of these diseases inclusive of ZIKV until a vaccine becomes available. PMID- 27679628 TI - Increasing resilience in adolescents: the importance of social connectedness in adventure education programmes. AB - OBJECTIVE: Mental health problems are a leading cause of health-related disability during adolescence. The objectives of the current study were to investigate whether participating in an adventure education programme (AEP) increased adolescents' resilience and elucidate how social connectedness contributes to any increase. METHOD: Adolescents who participated in the AEP had their resilience measured on the first (Time 1) and last day (Time 2) of a 10-day voyage. Perceived social support and sense of belonging were also measured at Time 2. A control group of adolescents, who did not take part in the voyage, also had their resilience assessed at two time points, 10 days apart. RESULT: Adolescents who participated in the AEP, but not those in the control group, displayed an increase in resilience from Time 1 to Time 2. Further, the increase in resilience was related to the adolescents' sense of belonging, and this effect held when controlling for perceived social support. CONCLUSION: These findings demonstrate the positive impact AEPs have on adolescents' resilience and a mechanism through which this occurs. PMID- 27679629 TI - Primary evidence of seton therapy at Tarban Creek, New South Wales, 1839. AB - OBJECTIVE: We aimed to find and explore the earliest available New South Wales asylum medical records to identify any management or therapeutic data that might be of interest to the psychiatric field. CONCLUSIONS: The earliest known existing records of New South Wales asylum data are from Tarban Creek Asylum. After almost two centuries the preserved records allow insight into treatment used in early colonial Australia, including the scarcely remembered seton therapy. This finding highlights the importance of preserving historical records. It also demonstrates the necessity and/or evolving wish within the colony to care for patients with perceived mental health difficulties based on a shared medical culture inherited from techniques used in Britain. PMID- 27679630 TI - Transference-Focused Psychotherapy in Australian psychiatric training and practice. AB - OBJECTIVE: This article discusses Transference-Focused Psychotherapy, a contemporary evidence-based and manualised form of psychoanalytic psychotherapy for borderline personality disorder. Transference focused psychotherapy has evolved from decades of research in the object-relations approach developed by Professor Otto Kernberg and his collaborators. It is being adopted increasingly throughout North and South America and Europe, and this article explores the role its adoption might play in psychiatric training as well as public and private service provision contexts in Australia. CONCLUSIONS: Transference focused psychotherapy is readily applicable in a range of training, research and public and private service provision contexts in Australia. A numbers of aspects of current Australian psychiatric training and practice, such as the Royal Australian and New Zealand College of Psychiatrists advanced training certificate, and the Australian medicare schedule, make it especially relevant for this purpose. PMID- 27679631 TI - Care or recovery? Redefining residential rehabilitation. AB - OBJECTIVE: The principles and practices underpinning a newly established community residential rehabilitation unit are described. CONCLUSIONS: Residential rehabilitation in mental health has largely operated under the same model of care for 25 years following the closure of the asylums. In keeping pace with the growing recovery movement led by consumers and their carers a new partnership model of care that promotes social inclusion and quality of life was considered desirable. PMID- 27679633 TI - When should I attempt my centrally administered summative assessments in the RANZCP competency-based training program? AB - OBJECTIVE: To provide information relevant to decision-making around the timing of attempting the centrally administered summative assessments in the Royal Australian and New Zealand College of Psychiatrists (RANZCP) 2012 Fellowship Program. METHODS: We consider the new Competency-Based Fellowship Program of the RANZCP and its underlying philosophy, the trainee trajectory within the program and the role of the supervisor. The relationship between workplace-based and external assessments is discussed. The timing of attempting centrally administered summative assessments is considered within the pedagogical framework of medical competencies development. RESULTS: Although successful completion of all the centrally administered summative assessments requires demonstration of a junior consultant standard of competency, the timing at which this standard will most commonly be achieved is likely to vary from assessment to assessment. There are disadvantages attendant upon prematurely attempting assessments, and trainees are advised to carefully consider the requirements of each assessment and match this against their current level of knowledge and skills. CONCLUSIONS: Trainees and supervisors need to be clear about the competencies required for each of the external assessments and match this against the trainee's current competencies to assist in decision-making about the timing of assessments and planning for future learning. PMID- 27679634 TI - Violence and self-harm in severe mental illness: inpatient study of associations with ethnicity, cannabis and alcohol. AB - OBJECTIVE: We examined the extent to which ethnicity, cannabis and alcohol use could predict prevalence of violence and self-harm in an inpatient psychiatric sample. METHOD: We collected demographic and clinical data in a series of 141 adult psychiatric inpatients in Hamilton, New Zealand. The Alcohol Use Disorders Identification Test (AUDIT) and Cannabis Use Disorders Identification Test, Revised (CUDIT-R) were used to measure substance use. Clinical assessment and file review were used to verify histories of self-harm and violence. RESULTS: It was found that 66% had a history of violence, 54% of self-harm, and 40% of both; only 20% had neither. Cannabis use was found to significantly predict lifetime history of violence ( p = 0.02); other independent variables (gender, age, ethnicity, alcohol use, psychiatric diagnosis) did not. Self-harm was strikingly predicted by female gender ( p < 0.001), as well as by measures both of cannabis ( p = 0.025) and alcohol use ( p = 0.036); age, ethnicity and diagnosis did not reach significance. Less than 10% of patients were engaged with drug or alcohol services. CONCLUSIONS: Cannabis use is a significant predictor of lifetime violence among the severely mentally ill, while both alcohol and cannabis use predict self-harm. Few affected patients receive specific treatment for substance use comorbidity. PMID- 27679635 TI - Establishment and implementation of a psychiatry enrichment programme for medical students. AB - OBJECTIVE: There has been a growing interest in psychiatry enrichment programmes such as summer schools and institutes for medical students in the last 10 years. Evaluation of enrichment programmes shows that they can be an effective method of increasing students' interest in psychiatry as a career. However, despite initial enthusiasm and motivation within an academic department, establishing a programme can be a daunting task. The aim of this paper is to provide a background of how to establish and implement a psychiatry summer school or institute. The steps that can be taken to establish and implement a psychiatry enrichment programme such as a summer school or institute are described and discussed. This includes how to structure a programme, content to include, costs and budget, programme promotion, selection of students and programme evaluation. CONCLUSION: Establishing an enrichment programme can provide academic departments of psychiatry with the opportunity to demonstrate excellence and innovation in teaching and positively promote psychiatry to students and other non-medical academics involved in medical education. For students interested in psychiatry, enrichment programmes have the potential to extend interest and knowledge beyond the curriculum and encourage serious consideration of psychiatry as a career. PMID- 27679636 TI - The misleading concept of initial severity in depression clinical trials: development and results from a mathematical model. AB - OBJECTIVE: Recently, meta-analytic studies have suggested a positive relationship between initial severity and magnitude of treatment efficacy. The aim of the current study was to develop a mathematical model to test the assumption concerning the role of initial severity in treatment response. METHODS: A number of experimental artificial datasets were developed on the basis of three different scenarios which reflect a pre-determined effect of initial severity. They were used to test for correlations at the patient level as well as at the meta-analysis level (trial level). RESULTS: The results suggested that in all scenarios and analyses the correlations were so high that a ceiling effect was obvious. The testing concerned changes from baseline, but not differences between arms. CONCLUSIONS: Overall the data suggest that the question concerning the role of initial severity cannot be answered. Any allegations on such a role are based on flawed methodology and do not take into consideration the true nature of data. PMID- 27679637 TI - Fixing a Hole: Preventing Pneumococcal Pneumonia by Vaccination. PMID- 27679638 TI - Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation. AB - Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF alpha, IL-6, IL-17A, and IFN-gamma). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n 3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis. PMID- 27679639 TI - Alkali-Soluble Pectin Is the Primary Target of Aluminum Immobilization in Root Border Cells of Pea (Pisum sativum). AB - We investigated the hypothesis that a discrepancy of Al binding in cell wall constituents determines Al mobility in root border cells (RBCs) of pea (Pisum sativum), which provides protection for RBCs and root apices under Al toxicity. Plants of pea (P. sativum L. 'Zhongwan no. 6') were subjected to Al treatments under mist culture. The concentration of Al in RBCs was much higher than that in the root apex. The Al content in RBCs surrounding one root apex (10(4) RBCs) was approximately 24.5% of the total Al in the root apex (0-2.5 mm), indicating a shielding role of RBCs for the root apex under Al toxicity. Cell wall analysis showed that Al accumulated predominantly in alkali-soluble pectin (pectin 2) of RBCs. This could be attributed to a significant increase of uronic acids under Al toxicity, higher capacity of Al adsorption in pectin 2 [5.3-fold higher than that of chelate-soluble pectin (pectin 1)], and lower ratio of Al desorption from pectin 2 (8.5%) compared with pectin 1 (68.5%). These results indicate that pectin 2 is the primary target of Al immobilization in RBCs of pea, which impairs Al access to the intracellular space of RBCs and mobility to root apices, and therefore protects root apices and RBCs from Al toxicity. PMID- 27679641 TI - GMATA: An Integrated Software Package for Genome-Scale SSR Mining, Marker Development and Viewing. AB - Simple sequence repeats (SSRs), also referred to as microsatellites, are highly variable tandem DNAs that are widely used as genetic markers. The increasing availability of whole-genome and transcript sequences provides information resources for SSR marker development. However, efficient software is required to efficiently identify and display SSR information along with other gene features at a genome scale. We developed novel software package Genome-wide Microsatellite Analyzing Tool Package (GMATA) integrating SSR mining, statistical analysis and plotting, marker design, polymorphism screening and marker transferability, and enabled simultaneously display SSR markers with other genome features. GMATA applies novel strategies for SSR analysis and primer design in large genomes, which allows GMATA to perform faster calculation and provides more accurate results than existing tools. Our package is also capable of processing DNA sequences of any size on a standard computer. GMATA is user friendly, only requires mouse clicks or types inputs on the command line, and is executable in multiple computing platforms. We demonstrated the application of GMATA in plants genomes and reveal a novel distribution pattern of SSRs in 15 grass genomes. The most abundant motifs are dimer GA/TC, the A/T monomer and the GCG/CGC trimer, rather than the rich G/C content in DNA sequence. We also revealed that SSR count is a linear to the chromosome length in fully assembled grass genomes. GMATA represents a powerful application tool that facilitates genomic sequence analyses. GAMTA is freely available at http://sourceforge.net/projects/gmata/?source=navbar. PMID- 27679640 TI - Methylglyoxal: An Emerging Signaling Molecule in Plant Abiotic Stress Responses and Tolerance. AB - The oxygenated short aldehyde methylglyoxal (MG) is produced in plants as a by product of a number of metabolic reactions, including elimination of phosphate groups from glycolysis intermediates dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. MG is mostly detoxified by the combined actions of the enzymes glyoxalase I and glyoxalase II that together with glutathione make up the glyoxalase system. Under normal growth conditions, basal levels of MG remain low in plants; however, when plants are exposed to abiotic stress, MG can accumulate to much higher levels. Stress-induced MG functions as a toxic molecule, inhibiting different developmental processes, including seed germination, photosynthesis and root growth, whereas MG, at low levels, acts as an important signaling molecule, involved in regulating diverse events, such as cell proliferation and survival, control of the redox status of cells, and many other aspects of general metabolism and cellular homeostases. MG can modulate plant stress responses by regulating stomatal opening and closure, the production of reactive oxygen species, cytosolic calcium ion concentrations, the activation of inward rectifying potassium channels and the expression of many stress responsive genes. MG appears to play important roles in signal transduction by transmitting and amplifying cellular signals and functions that promote adaptation of plants growing under adverse environmental conditions. Thus, MG is now considered as a potential biochemical marker for plant abiotic stress tolerance, and is receiving considerable attention by the scientific community. In this review, we will summarize recent findings regarding MG metabolism in plants under abiotic stress, and evaluate the concept of MG signaling. In addition, we will demonstrate the importance of giving consideration to MG metabolism and the glyoxalase system, when investigating plant adaptation and responses to various environmental stresses. PMID- 27679642 TI - Vacuolar Iron Transporter BnMEB2 Is Involved in Enhancing Iron Tolerance of Brassica napus. AB - Iron toxicity is a nutrient disorder that severely affects crop development and yield in some soil conditions. Vacuolar detoxification of metal stress is an important strategy for plants to survive and adapt to this adverse environment. Vacuolar iron transporter (VIT) members are involved in this process and play essential roles in iron storage and transport. In this study, we identified a rapeseed VIT gene BnMEB2 (BnaC07g30170D) homologs to Arabidopsis MEB2 (At5g24290). Transient expression analysis revealed that BnMEB2 was localized to the vacuolar membrane. Q-PCR detection showed a high expression of BnMEB2 in mature (60-day-old) leaves and could be obviously induced by exogenous iron stress in both roots and leaves. Over-expressed BnMEB2 in both Arabidopsis wild type and meb2 mutant seedlings resulted in greatly improved iron tolerability with no significant changes in the expression level of other VIT genes. The mutant meb2 grew slowly and its root hair elongation was inhibited under high iron concentration condition while BnMEB2 over-expressed transgenic plants of the mutant restored the phenotypes with apparently higher iron storage in roots and dramatically increased iron content in the whole plant. Taken together, these results suggested that BnMEB2 was a VIT gene in rapeseed which was necessary for safe storage and vacuole detoxification function of excess iron to enhance the tolerance of iron toxicity. This research sheds light on a potentially new strategy for attenuating hazardous metal stress from environment and improving iron biofortification in Brassicaceae crops. PMID- 27679643 TI - Plant Tolerance: A Unique Approach to Control Hemipteran Pests. AB - Plant tolerance to insect pests has been indicated to be a unique category of resistance, however, very little information is available on the mechanism of tolerance against insect pests. Tolerance is distinctive in terms of the plant's ability to withstand or recover from herbivore injury through growth and compensatory physiological processes. Because plant tolerance involves plant compensatory characteristics, the plant is able to harbor large numbers of herbivores without interfering with the insect pest's physiology or behavior. Some studies have observed that tolerant plants can compensate photosynthetically by avoiding feedback inhibition and impaired electron flow through photosystem II that occurs as a result of insect feeding. Similarly, the up-regulation of peroxidases and other oxidative enzymes during insect feeding, in conjunction with elevated levels of phytohormones can play an important role in providing plant tolerance to insect pests. Hemipteran insects comprise some of the most economically important plant pests (e.g., aphids, whiteflies), due to their ability to achieve high population growth and their potential to transmit plant viruses. In this review, results from studies on plant tolerance to hemipterans are summarized, and potential models to understand tolerance are presented. PMID- 27679645 TI - Halophytes As Bioenergy Crops. AB - Shrinking arable land due to soil salinization and, depleting fresh water resources pose serious worldwide constraints to crop productivity. A vision of using plant feedstock for biofuel production can only be realized if we can identify alternate species that can be grown on saline soils and therefore, would not compete for the resources required for conventional agriculture. Halophytes have remarkable ability to grow under high salinity conditions. They can be irrigated with seawater without compromising their biomass and seed yields making them good alternate candidates as bioenergy crops. Both oil produced from the seeds and the lignocellulosic biomass of halophytes can be utilized for biofuel production. Several researchers across the globe have recognized this potential and assessed several halophytes for their tolerance to salt, seed oil contents and composition of their lignocellulosic biomass. Here, we review current advances and highlight the key species of halophytes analyzed for this purpose. We have critically assessed the challenges and opportunities associated with using halophytes as bioenergy crops. PMID- 27679644 TI - Isolation and Functional Characterization of a Lycopene beta-cyclase Gene Promoter from Citrus. AB - Lycopene beta-cyclases are key enzymes located at the branch point of the carotenoid biosynthesis pathway. However, the transcriptional regulatory mechanisms of LCYb1 in citrus with abundant carotenoid accumulation are still unclear. To understand the molecular basis of CsLCYb1 expression, we isolated and functionally characterized the 5' upstream sequences of CsLCYb1 from citrus. The full-length CsLCYb1 promoter and a series of its 5' deletions were fused to the beta-glucuronidase (GUS) reporter gene and transferred into different plants (tomato, Arabidopsis and citrus callus) to test the promoter activities. The results of all transgenic species showed that the 1584 bp upstream region from the translational start site displayed maximal promoter activity, and the minimal promoter containing 746 bp upstream sequences was sufficient for strong basal promoter activity. Furthermore, the CsLCYb1 promoter activity was developmentally and tissue-specially regulated in transgenic Arabidopsis, and it was affected by multiple hormones and environmental cues in transgenic citrus callus under various treatments. Finer deletion analysis identified an enhancer element existing as a tandem repeat in the promoter region between -574 to -513 bp and conferring strong promoter activity. The copy numbers of the enhancer element differed among various citrus species, leading to the development of a derived simple sequence repeat marker to distinguish different species. In conclusion, this study elucidates the expression characteristics of the LCYb1 promoter from citrus and further identifies a novel enhancer element required for the promoter activity. The characterized promoter fragment would be an ideal candidate for genetic engineering and seeking of upstream trans-acting elements. PMID- 27679646 TI - Selection of Reference Genes for Quantitative Real-Time RT-PCR Studies in Tomato Fruit of the Genotype MT-Rg1. AB - Quantitative real-time RT-PCR (qRT-PCR) has become one of the most widely used methods for accurate quantification of gene expression. Since there are no universal reference genes for normalization, the optimal strategy to normalize raw qRT-PCR data is to perform an initial comparison of a set of independent reference genes to assess the most stable ones in each biological model. Normalization of a qRT-PCR experiment helps to ensure that the results are both statistically significant and biologically meaningful. Tomato is the model of choice to study fleshy fruit development. The miniature tomato (Solanum lycopersicum L.) cultivar Micro-Tom (MT) is considered a model system for tomato genetics and functional genomics. A new genotype, containing the Rg1 allele, improves tomato in vitro regeneration. In this work, we evaluated the expression stability of four tomato reference genes, namely CAC, SAND, Expressed, and ACTIN2. We showed that the genes CAC and Exp are the best reference genes of the four we tested during fruit development in the MT-Rg1 genotype. Furthermore, we validated the reference genes by showing that the expression profiles of the transcription factors FRUITFULL1 and APETALA2c during fruit development are comparable to previous reports using other tomato cultivars. PMID- 27679647 TI - Comparison of Metabolic and Hormonal Profiles of Women With and Without Premenstrual Syndrome: A Community Based Cross-Sectional Study. AB - BACKGROUND: Premenstrual syndrome (PMS) is reported by up to 85% of women of reproductive age. Although several studies have focused on the hormone and lipid profiles of females with PMS, the results are controversial. OBJECTIVES: This study was designed to investigate the association of hormonal and metabolic factors with PMS among Iranian women of reproductive age. MATERIALS AND METHODS: This study was a community based cross-sectional study. Anthropometric measurements, biochemical parameters, and metabolic disorders were compared between 354 women with PMS and 302 healthy controls selected from among 1126 women of reproductive age who participated in the Iranian PCOS prevalence study. P values < 0.05 were considered significant. RESULTS: Prolactin (PRL) and triglycerides (TG) were significantly elevated in women with PMS, whereas their testosterone (TES), high density lipoprotein (HDL) and 17-hydroxyprogesterone (17 OHP) levels were significantly less than they were in women without the syndrome (P < 0.05). After adjusting for age and body mass index (BMI), linear regression analysis demonstrated that for every one unit increase in PMS score there was 12% rise in the probability of having metabolic syndrome (P = 0.033). CONCLUSIONS: There was a significant association between PMS scores and the prevalence of metabolic syndrome. Further studies are needed to confirm and validate the relationships between lipid profile abnormalities and metabolic disorders with PMS. PMID- 27679648 TI - Lipodistrophy and Associated Risk Factors in Insulin-Treated People With Diabetes. PMID- 27679649 TI - The Impact of Vitamin D Supplementation on Post-Partum Glucose Tolerance and Insulin Resistance in Gestational Diabetes: A Randomized Controlled Trial. AB - BACKGROUND: Hypovitaminosis D has been associated with the development of gestational diabetes mellitus (GDM) in many observational studies. OBJECTIVES: We report the first study of the impact of prenatal vitamin D supplementation on postpartum dysglycemia in GDM patients in a randomized clinical trial. PATIENTS AND METHODS: Women with GDM at 12 - 32 weeks of gestation were assigned randomly to either the intervention group (in which serum 25-hydroxy vitamin D [25OHD] levels were measured immediately, n = 48) or the control group (in which the serum was stored and assayed at 6 - 12 weeks post-partum, n = 48). Participants with initial serum 25OHD < 30 ng/mL in the intervention group were instructed to take a total of 700,000 IU vitamin D3 during pregnancy. The primary outcomes were fasting plasma glucose (FPG), insulin, 2-h post 75 g glucose load plasma glucose (2-hPLG), homeostasis model assessment of insulin resistance (HOMA-IR), HbA1C, and 25 OHD at 6 - 12 weeks after delivery. RESULTS: The mean +/- SD of serum 25OHD in the intervention group raised dramatically from 14.6 +/- 6.3 to 32.4 +/- 14.4 ng/mL, whereas no significant change occurred in the control group (from 17.7 +/- 6.1 to 19.3 +/- 9.6 ng/mL, P < 0.001). Thirteen participants developed dysglycemia in each group. Mean FPG, 2-hPLG, and HOMA-IR were not significantly different between the groups. There was no significant difference between the groups for maternal and neonatal outcomes. CONCLUSIONS: Although the high vitamin D supplementation dose in the present study (compared to the 400 IU/day dose usually recommended for pregnancy) safely increases the serum 25OHD, in GDM cases, the higher dose does not affect the plasma glucose level or insulin resistance at short term follow-up after delivery. PMID- 27679650 TI - Comparison of the Vitamin D Status of Children Younger and Older Than 2 Years in Tehran: Are Supplements Really Necessary? AB - BACKGROUND: Vitamin D is a vital lipid-soluble vitamin in the body, helping the growth and development of bones. Vitamin D deficiency in children has several adverse effects. The most important preventative factor is determining the deficiency at an early stage and prescribing vitamin D-containing supplements. OBJECTIVES: To investigate the vitamin D status of children younger and older than 2 years and determine the utility of prescribing vitamin D supplements. PATIENTS AND METHODS: Three hundred healthy children who attended the pediatric clinic for routine assessments were enrolled in this study. Their parents were asked to complete a questionnaire, which included questions about demographics, nutrition, and supplements. Blood levels of vitamin D, calcium, and phosphorus were then measured. RESULTS: The final study consisted of 286 children, 140 males and 146 females, with a mean age of 4.46 +/- 2.82 yr. Of these, 218 (76.22%) children, with a mean age of 5.09 +/- 2.82 yr, had vitamin D deficiency, and 76 children (23.78%), with a mean age of 2.58 +/- 1.88 yr, had normal vitamin D levels (P = 0.001). The mean level of vitamin D was 29.71 +/- 14.42 ng/mL in 88 (30.8%) patients up to 2 years and 17.11 +/- 14.02 ng/mL in 198 (69.2%) patients older than 2 years (P = 0.0001). CONCLUSIONS: The vitamin D levels of children aged more than 2 years are lower than those of children aged less than 2 years. Thus, prescribing vitamin D-containing supplements in children older than 2 years may be beneficial. PMID- 27679651 TI - Recurrence of Hyperparathyroid Hypercalcemia in a Patient With the HRPT-2 Mutation and a Previous Parathyroid Carcinoma in Hyperparathyroidism-Jaw Tumor Syndrome. AB - INTRODUCTION: Cancer in the parathyroid gland is rare, but parathyroid cancer is occasionally seen in relation to genetic abnormalities. Due to a limited amount of evidence, the optimal handling of these cases is not clear. Furthermore, the presence of a malignant parathyroid tumor is rarely known at the time of the initial operation; therefore, re-operations are often necessary. The aim of this study was to present the case of a patient with a previously diagnosed jaw tumor and parathyroid carcinoma that presents as a recurrence of hyperparathyroid hypercalcemia. CASE PRESENTATION: A 41-year-old patient who was already diagnosed with a parathyroid carcinoma and a jaw tumor caused by a CDC73 mutation, presented with biochemical evidence of increasing parathyroid hormone (PTH) and calcium levels after a previous total parathyroidectomy. The patient's ionized calcium increased to 1.55 mmol/L and PTH increased to 16.0 pmol/L. A previous genetic analysis revealed a mutation in the CDC73 gene. There was no family history of hyperparathyroidism. We performed a sestamibi scintigraphy and an 11-C methionine (MET) positron emission tomography (PET) scan that showed a recurrence on the left side of the trachea. The patient underwent a third neck operation for the removal of a tumor on the left side of the trachea. The pathology report revealed that the tumor was a lymph node metastasis from the previous parathyroid carcinoma. The patient is currently enrolled in our follow-up regime. Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal dominant disorder characterized by a parathyroid adenoma or carcinoma, fibro-osseous lesions (ossifying fibroma) of the mandible and maxilla, and renal cysts and tumors. This autosomal dominant familial cancer syndrome has been reported with a variable and incomplete penetrance, and up to 10% of gene carriers do not show any clinical manifestations. Here we present a patient's case and discuss the literature related to this condition. CONCLUSIONS: The recurrence of hyperparathyroid hypercalcemia in HTP-JT syndrome after an initial total parathyroidectomy is a well-known condition necessitating careful management, an evaluation of any underlying genetic abnormality, and a family examination. A surgical treatment and surveillance of calcium and PTH measurements are necessary to prevent a recurrence. PMID- 27679652 TI - Care of the Athlete With Type 1 Diabetes Mellitus: A Clinical Review. AB - CONTEXT: Type 1 diabetes mellitus (T1DM) results from a highly specific immune mediated destruction of pancreatic beta cells, resulting in chronic hyperglycemia. For many years, one of the mainstays of therapy for patients with T1DM has been exercise balanced with appropriate medications and medical nutrition. Compared to healthy peers, athletes with T1DM experience nearly all the same health-related benefits from exercise. Despite these benefits, effective management of the T1DM athlete is a constant challenge due to various concerns such as the increased risk of hypoglycemia. This review seeks to summarize the available literature and aid clinicians in clinical decision-making for this patient population. EVIDENCE ACQUISITION: PubMed searches were conducted for "type 1 diabetes mellitus AND athlete" along with "type 1 diabetes mellitus AND exercise" from database inception through November 2015. All articles identified by this search were reviewed if the article text was available in English and related to management of athletes with type 1 diabetes mellitus. Subsequent reference searches of retrieved articles yielded additional literature included in this review. RESULTS: The majority of current literature available exists as recommendations, review articles, or proposed societal guidelines, with less prospective or higher-order treatment studies available. The available literature is presented objectively with an attempt to describe clinically relevant trends and findings in the management of athletes living with T1DM. CONCLUSIONS: Managing T1DM in the context of exercise or athletic competition is a challenging but important skill for athletes living with this disease. A proper understanding of the hormonal milieu during exercise, special nutritional needs, glycemic control, necessary insulin dosing adjustments, and prevention/management strategies for exercise-related complications can lead to successful care plans for these patients. Individualized management strategies should be created with close cooperation between the T1DM athlete and their healthcare team (including a physician and dietitian). PMID- 27679654 TI - Enumeration of minimal stoichiometric precursor sets in metabolic networks. AB - BACKGROUND: What an organism needs at least from its environment to produce a set of metabolites, e.g. target(s) of interest and/or biomass, has been called a minimal precursor set. Early approaches to enumerate all minimal precursor sets took into account only the topology of the metabolic network (topological precursor sets). Due to cycles and the stoichiometric values of the reactions, it is often not possible to produce the target(s) from a topological precursor set in the sense that there is no feasible flux. Although considering the stoichiometry makes the problem harder, it enables to obtain biologically reasonable precursor sets that we call stoichiometric. Recently a method to enumerate all minimal stoichiometric precursor sets was proposed in the literature. The relationship between topological and stoichiometric precursor sets had however not yet been studied. RESULTS: Such relationship between topological and stoichiometric precursor sets is highlighted. We also present two algorithms that enumerate all minimal stoichiometric precursor sets. The first one is of theoretical interest only and is based on the above mentioned relationship. The second approach solves a series of mixed integer linear programming problems. We compared the computed minimal precursor sets to experimentally obtained growth media of several Escherichia coli strains using genome-scale metabolic networks. CONCLUSIONS: The results show that the second approach efficiently enumerates minimal precursor sets taking stoichiometry into account, and allows for broad in silico studies of strains or species interactions that may help to understand e.g. pathotype and niche-specific metabolic capabilities. sasita is written in Java, uses cplex as LP solver and can be downloaded together with all networks and input files used in this paper at http://www.sasita.gforge.inria.fr. PMID- 27679655 TI - Why Medecins Sans Frontieres (MSF) provides safe abortion care and what that involves. AB - MSF responds to needs for the termination of pregnancy, including on request (TPR); it is part of the organization's work aimed at reducing maternal mortality and suffering; and preventing unsafe abortions in the countries where we work. Following the publication of "Why don't humanitarian organizations provide safe abortion care?" we offer an insight into MSF's experience over the past few years. The article looks at the legal concerns and proposes that the importance of addressing maternal mortality should replace them and the operational set-up and action organized in a way that mitigates risks. MSF took a policy decision on safe abortion care in 2004; the fact that care did not expand rapidly to relevant MSF projects came as a surprise, reflecting the important weight social norms around abortion have everywhere. The need to engage in an open dialogue with staff, relevant medical actors and at community level became more obvious. Finally the article looks some key lessons that have emerged for the organization as part of the effort to prevent ill health, maternal death and suffering caused by unwanted pregnancy and unsafe abortion. PMID- 27679656 TI - Do people's goals for mass participation sporting events matter? A self determination theory perspective. AB - Background: Non-elite mass participation sports events (MPSEs) may hold potential as a physical activity promotion tool. Research into why people participate in these events and what goals they are pursuing is lacking. Grounded in self determination theory, this study examined the associations between MPSE participants' goals, event experiences and physical activity. Methods: A prospective cohort study was conducted; pre-event, participants reported their goals for the event. Four weeks post-event, participants reported their motivation for exercise, perceptions of their event achievement and moderate-to vigorous intensity physical activity (MVPA). Bivariate correlations and path analysis were performed on data from 114 adults. Results: Intrinsic goals (e.g. health, skill and social affiliation) for the event were positively associated with perceptions of event achievement, whereas extrinsic goals (e.g. appearance or social recognition) were not. Event achievement was positively associated with post-event autonomous motivation, which in turn was positively associated with MVPA. Conclusions: Pursuing intrinsic but not extrinsic goals for MPSEs is associated with greater perceptions of event achievement, which in turn is associated with post-event autonomous motivation and MVPA. PMID- 27679653 TI - The Arabidopsis CERK1-associated kinase PBL27 connects chitin perception to MAPK activation. AB - Perception of microbe-associated molecular patterns by host cell surface pattern recognition receptors (PRRs) triggers the intracellular activation of mitogen activated protein kinase (MAPK) cascades. However, it is not known how PRRs transmit immune signals to MAPK cascades in plants. Here, we identify a complete phospho-signaling transduction pathway from PRR-mediated pathogen recognition to MAPK activation in plants. We found that the receptor-like cytoplasmic kinase PBL27 connects the chitin receptor complex CERK1-LYK5 and a MAPK cascade. PBL27 interacts with both CERK1 and the MAPK kinase kinase MAPKKK5 at the plasma membrane. Knockout mutants of MAPKKK5 compromise chitin-induced MAPK activation and disease resistance to Alternaria brassicicola PBL27 phosphorylates MAPKKK5 in vitro, which is enhanced by phosphorylation of PBL27 by CERK1. The chitin perception induces disassociation between PBL27 and MAPKKK5 in vivo Furthermore, genetic evidence suggests that phosphorylation of MAPKKK5 by PBL27 is essential for chitin-induced MAPK activation in plants. These data indicate that PBL27 is the MAPKKK kinase that provides the missing link between the cell surface chitin receptor and the intracellular MAPK cascade in plants. PMID- 27679657 TI - Portrayal of tobacco smoking in popular women's magazines: a content analysis. AB - Background: Whilst many countries have introduced legislation prohibiting tobacco advertising and sponsorship, references to tobacco continue to appear in the media. This study quantified and characterized tobacco smoking content in popular women's magazines. Methods: The 10 top weekly and 5 monthly women's magazines most popular among 15-34 year olds in Britain published over a 3-month period were included. A content analysis was conducted for both written and visual content. Results: In 146 magazines, there were 310 instances of tobacco content, the majority of which were positive towards smoking. Instances of celebrities smoking were most common (171, 55%), often in holiday or party settings that could be perceived to be luxurious, glamorous or fun. In all, 55 (18%) tobacco references related to fashion, which generally created an impression of smoking as a norm within the industry; and 34 (11%) text and image references to tobacco in TV and film. There were 50 (16%) reader-initiated mentions of smoking, typically in real-life stories or readers writing in to seek advice about smoking. Anti-smoking references including the hazards of smoking were infrequent (49; 16%). Conclusions: Although tobacco advertising is prohibited in Britain, women's magazines still appear to be promoting positive messages about tobacco and smoking. PMID- 27679659 TI - Maternal nutrient intakes from food and drinks consumed in early pregnancy in Ireland. AB - Background: The aim of this observational study was to measure food, macronutrient and micronutrient intakes of women presenting for antenatal care and assess compliance with current nutritional recommendations. Methods: Women were recruited in the first trimester of pregnancy. Maternal weight and height were measured and body mass index (BMI) calculated. Body composition was measured using bioelectrical impedance analysis. Maternal energy and nutrient intakes were estimated using a validated Willett Food Frequency Questionnaire and misreporting of energy intakes (EI) determined. Results: Plausible EIs were reported in 402 women. Mean age, weight and BMI were 30.8 years, 67.1 kg and 24.6 kg/m2 respectively. Median EIs were 2111 kcal, and median protein, carbohydrate and fat intakes were 17.3, 48.1 and 36.2 g/MJ/day, respectively. More than 90% of women exceeded the recommended daily allowance for saturated fat. Nearly all of the women (99%) did not meet estimated average requirements (EAR) for vitamin D. One in three women failed to achieve a dietary folate intake of 400 ug/day. Over one in five women failed to meet the EAR for iron, and 14% failed to achieve the EAR for calcium. Conclusions: Our findings highlight concerning deficits in nutrient intakes among women and will help guide professional dietary advice to women attending for future obstetric care in Ireland. PMID- 27679658 TI - Education and disability trends of older Americans, 2000-2014. AB - Background: Trends in disability among older Americans has declined since the 1980s. The study examines whether the trend continues to decline and whether educational disparities exist in the prevalence of functional limitations. Methods: I used the 2000-2014 National Health Interview Survey and included adults aged >=65 years. Functional limitations was measured by three outcomes: the need for help with activities of daily living (ADLs) or instrumental activities of daily living (IADLs) and physical function limitations. I used a set of logistic models to estimate the average annual change rate of functional limitations. I examined whether the annual rate of change differed by education, age group and sex. Results: During 2000-2014, the annual increase rate of ADL limitations was 1.7% (P < 0.001) and was 2.0% (P < 0.001) for physical function limitations; IADL limitation did not change significantly. All subgroups experienced an increase in ADL and physical function limitations except for adults with a more than high school education. The lower-educated group had a higher proportion and a higher annual rate of increase in all outcomes. Increasing trends in chronic conditions may contribute to the increasing trend in functional limitations. Conclusions: The study highlighted a large educational disparity in late-life disability among older Americans. PMID- 27679660 TI - Papillomavirus and cancers: should we extend vaccination to boys in France? AB - Background: In 2006, the HPV (Human papillomavirus) 6/11/16/18 quadrivalent vaccine was approved by the European Medicines Agency and obtained its marketing authorization in both girls and boys. Currently, the French guidelines recommend and refund vaccination of girls aged 11 to 14 with a catch-up program for females from 15 to 19 years old. Discussion: In France, HPV vaccination coverage tends to decrease. At the end of 2015, the vaccination coverage with three doses reached only 14% in 16-year-old girls (three doses). Although men are also affected by HPV-related diseases such as anal cancer, ano-genital warts, penile cancer or upper aerodigestive tract cancer, vaccine recommendations in France are for girls only. To face the high prevalence of anal cancer and related diseases, the best option is vaccination. Moreover, by offering men a way to prevent diseases against which they do not have any protection yet, universal vaccination could better take into account the ethical issues of prevention. In this paper, we present the point of view of different medical specialties concerning the potential benefit of extending vaccination to boys. Conclusion: HPV vaccination of both genders could benefit from a better public acceptance and contribute to a better coverage, especially in countries with low vaccination rates. PMID- 27679662 TI - Dispositional pandemic worry and the health belief model: promoting vaccination during pandemic events. AB - Background: Promoting vaccination during pandemics is paramount to public health, yet few studies examined theoretical motivations for vaccination during pandemics. Thus, the relationships between dispositional pandemic worry, constructs of the health belief model (HBM) and vaccination during the H1N1 pandemic were studied. Methods: Participants (N = 1377) completed surveys assessing dispositional pandemic worry, HBM variables and H1N1 vaccination. Principle axis factor analysis and point biserial correlations were conducted. Differences in worry and vaccination were assessed via independent samples t tests. Relationships between vaccination, demographics and worry were investigated using hierarchical linear regression. PROCESS analysis was conducted to explicate the relationship between worry and vaccination intention. Results: A two-factor structure of dispositional pandemic worry-worry frequency and worry severity-was confirmed. Dispositional worry was higher among those who intended to and received H1N1 vaccine. Worry frequency and worry severity were positively related to vaccination. Threat, benefits and barriers mediated the impact of worry severity and threat and barriers mediated the impact of worry frequency on vaccination intentions. Conclusions: Messages increasing dispositional worry and benefits while decreasing barriers may boost vaccination behavior during a pandemic event. Future study of relationships between dispositional worry and HBM variables is warranted. PMID- 27679661 TI - A content analysis of the UK press response to the diagnosis of Ebola in a British healthcare worker. AB - Background: The Ebola epidemic led to considerable media attention, which may influence public risk perception. Therefore, this study analysed the UK press response following diagnosis of a British healthcare worker (HCW) with Ebola. Methods: Using the Nexis database, the frequency of Ebola-related articles in UK national newspaper articles was mapped. This was followed by a content analysis of Ebola-related articles in the four newspapers with highest UK net readership from November 2014 to February 2015. Results: During the 16-week study period, 1349 articles were found. The day with the highest number of Ebola-related articles was 31 December 2014, the day after the diagnosis of Ebola in a UK HCW. Seventy-seven articles were included in the content analysis. Content analysis demonstrated a shift from West African to UK-focused articles, increased discussion of border control, UK policy decisions and criticism, and an increased number of articles with a reassuring/threatening message. Conclusions: UK press coverage of Ebola increased following a HCW's diagnosis, particularly regarding discussion of screening measures. This is likely to have increased risk perception of Ebola in the UK population and may have contributed to subsequent strengthening of UK screening policy beyond World Health Organisation requirements. PMID- 27679663 TI - Investigating what works to support family carers of people with dementia: a rapid realist review. AB - Introduction: Advances in longevity and medicine mean that many more people in the UK survive life-threatening diseases but are instead susceptible to life limiting diseases such as dementia. Within the next 10 years those affected by dementia in the UK is set to rise to over 1 million, making reliance on family care of people with dementia (PWD) essential. A central challenge is how to improve family carer support to offset the demands made by dementia care which can jeopardise carers' own health. This review investigates 'what works to support family carers of PWD'. Methods: Rapid realist review of a comprehensive range of databases. Results: Five key themes emerged: (1) extending social assets, (2) strengthening key psychological resources, (3) maintaining physical health status, (4) safeguarding quality of life and (5) ensuring timely availability of key external resources. It is hypothesized that these five factors combine and interact to provide critical biopsychosocial and service support that bolsters carer 'resilience' and supports the maintenance and sustenance of family care of PWD. Conclusions: 'Resilience-building' is central to 'what works to support family carers of PWD'. The resulting model and Programme Theories respond to the burgeoning need for a coherent approach to carer support. PMID- 27679664 TI - The cost effectiveness of the SIMPle intervention to improve antimicrobial prescribing for urinary tract infection in primary care. AB - Background: Antimicrobial resistance is a major public health issue. This study examines the cost effectiveness of the SIMPle (Supporting the Improvement and Management of Prescribing for Urinary Tract Infections (UTI)) intervention to improve antimicrobial prescribing in primary care in Ireland. Methods: An economic evaluation was conducted alongside a cluster randomized controlled trial of 30 general practices and 2560 patients with a diagnosis of UTI. Practices were randomized to the usual practice control or the SIMPle intervention (arm A or B). Data at 6 months follow-up were used to estimate incremental costs, incremental effectiveness in terms of first-line antimicrobial prescribing for UTI and cost effectiveness acceptability curves. Results: The SIMPle intervention was, on average, more costly and more effective than the control. The probability of intervention arm A being cost effective was 0.280, 0.995 and 1.000 at threshold values of ?50, ?150 and ?250 per percentage point increase in first-line antimicrobial prescribing respectively. The equivalent probabilities for intervention arm B were 0.121, 0.863 and 0.985, respectively. Conclusions: The cost effectiveness of the SIMPle intervention depends on the value placed on improving antimicrobial prescribing. Future studies should examine the wider and longer term costs and outcomes of improving antimicrobial prescribing. PMID- 27679666 TI - Most add-on therapies to metformin have similar effects on HbA1c. PMID- 27679665 TI - Associations of Acculturation With Self-Report and Objective Physical Activity and Sedentary Behaviors Among Latinas. AB - BACKGROUND: Less than 50% of Latinas meet physical activity (PA) recommendations. Acculturation is a complex cultural phenomenon that may influence health behaviors, but associations between acculturation and Latinas' activity and sedentary levels are unclear. AIM: To examine associations of acculturation with Latinas' domain-specific and total PA as well as sedentary time. METHOD: We analyzed baseline data collected between 2011 and 2013 among 410 Latinas (18-65 years) from a PA promotion intervention in San Diego, CA ( Fe en Accion/ Faith in Action). Participants wore an accelerometer to assess moderate-to-vigorous PA (MVPA) and sedentary time and completed a survey assessing domain-specific PA, sociodemographics, and acculturation as measured by length of residence in the United States and the Bidimensional Acculturation Scale (BAS) for Hispanics. Higher acculturation was defined as longer residence in the United States or being either assimilated or bicultural as per scores on the Hispanic and Anglo domains of the BAS. RESULTS: Based on weekly averages from the accelerometer, Latinas spent 103 minutes in MVPA and 76% of total activity in sedentary time. Only 32% met MVPA recommendations via self-reported leisure-time and transportation PA. Longer residence in the United States was inversely associated with reporting any transportation or occupational PA and meeting MVPA recommendations. Assimilated/bicultural Latinas had significantly less accelerometer-based total MVPA and higher sedentary time than their lower acculturated counterparts. CONCLUSIONS: Overall, higher acculturation, based on either measure, was related to less activity. Our findings suggest interventions tailored to the acculturation levels of Latinas are needed to help reduce disparities in Latinas' PA and sedentary behaviors. PMID- 27679667 TI - Careful monitoring of fetal growth and maternal nutritional status should be practiced in pregnant women with a history of bariatric surgery. PMID- 27679669 TI - The synthetic xylulose-1 phosphate pathway increases production of glycolic acid from xylose-rich sugar mixtures. AB - BACKGROUND: Glycolic acid (GA) is a two-carbon hydroxyacid with applications in the cosmetic, textile, and medical industry. Microbial GA production from all sugars can be achieved by engineering the natural glyoxylate shunt. The synthetic (d)-xylulose-1 phosphate (X1P) pathway provides a complementary route to produce GA from (d)-xylose. The simultaneous operation of the X1P and glyoxylate pathways increases the theoretical GA yield from xylose by 20 %, which may strongly improve GA production from hemicellulosic hydrolysates. RESULTS: We herein describe the construction of an E. coli strain that produces GA via the glyoxylate pathway at a yield of 0.31 , 0.29 , and 0.37 g/g from glucose, xylose, or a mixture of glucose and xylose (mass ratio: 33:66 %), respectively. When the X1P pathway operates in addition to the glyoxylate pathway, the GA yields on the three substrates are, respectively, 0.39 , 0.43 , and 0.47 g/g. Upon constitutive expression of the sugar permease GalP, the GA yield of the strain which simultaneously operates the glyoxylate and X1P pathways further increases to 0.63 g/g when growing on the glucose/xylose mixture. Under these conditions, the GA yield on the xylose fraction of the sugar mixture reaches 0.75 g/g, which is the highest yield reported to date. CONCLUSIONS: These results demonstrate that the synthetic X1P pathway has a very strong potential to improve GA production from xylose-rich hemicellulosic hydrolysates. PMID- 27679668 TI - Phenotypic characterization and comparative transcriptomics of evolved Saccharomyces cerevisiae strains with improved tolerance to lignocellulosic derived inhibitors. AB - BACKGROUND: Lignocellulosic biomass continues to be investigated as a viable source for bioethanol production. However, the pretreatment process generates inhibitory compounds that impair the growth and fermentation performance of microorganisms such as Saccharomyces cerevisiae. Pinewood specifically has been shown to be challenging in obtaining industrially relevant ethanol titers. An industrial S. cerevisiae strain was subjected to directed evolution and adaptation in pretreated pine biomass and resultant strains, GHP1 and GHP4, exhibited improved growth and fermentative ability on pretreated pine in the presence of related inhibitory compounds. A comparative transcriptomic approach was applied to identify and characterize differences in phenotypic stability of evolved strains. RESULTS: Evolved strains displayed different fermentative capabilities with pretreated pine that appear to be influenced by the addition or absence of 13 inhibitory compounds during pre-culturing. GHP4 performance was consistent independent of culturing conditions, while GHP1 performance was dependent on culturing with inhibitors. Comparative transcriptomics revealed 52 genes potentially associated with stress responses to multiple inhibitors simultaneously. Fluorescence microscopy revealed improved cellular integrity of both strains with mitochondria exhibiting resistance to the damaging effects of inhibitors in contrast to the parent. CONCLUSIONS: Multiple potentially novel genetic targets have been discovered for understanding stress tolerance through the characterization of our evolved strains. This study specifically examines the synergistic effects of multiple inhibitors and identified targets will guide future studies in remediating effects of inhibitors and further development of robust yeast strains for multiple industrial applications. PMID- 27679670 TI - Nucleosome distortion as a possible mechanism of transcription activation domain function. AB - After more than three decades since the discovery of transcription activation domains (ADs) in gene-specific activators, the mechanism of their function remains enigmatic. The widely accepted model of direct recruitment by ADs of co activators and basal transcriptional machinery components, however, is not always compatible with the short size yet very high degree of sequence randomness and intrinsic structural disorder of natural and synthetic ADs. In this review, we formulate the basis for an alternative and complementary model, whereby sequence randomness and intrinsic structural disorder of ADs are necessary for transient distorting interactions with promoter nucleosomes, triggering promoter nucleosome translocation and subsequently gene activation. PMID- 27679672 TI - Environmental and lifestyle risk factors of breast cancer in Malta-a retrospective case-control study. AB - AIM AND BACKGROUND: Environmental exposures are known to play a role in the development of cancer, including breast cancer. There are known associations of breast cancer with environmental factors such as sunlight exposure, diet and exercise and alcohol consumption as well as physiological factors. This study examines the prevalence of risk factors for breast cancer related to dietary intake, environment and lifestyle in the female population of Malta. Malta has had little research in this area, and therefore an exploratory study was carried out. METHODS: A retrospective case-control design was applied. Two hundred cases and 403 controls were included. Both cases and controls were subjects without a known family history for breast cancer. Controls were age-matched to cases in an age-decade category roughly at a 2:1 ratio. Interviews were carried out face-to face using a questionnaire designed by Maltese and Sicilian researchers, encompassing various factors including diet, lifestyle, physiological factors and medical history. Breast cancer risk was then analysed using both univariate and multivariate analyses. For factors having a metric scale, the Mann-Whitney test was used to compare mean scores, while for categorical factors, the chi-square test was used to compare percentages between the case and control groups. Statistical modelling was carried out using binary logistic regression to relate the likelihood of breast cancer to over 50 risk/protective factors analysed collectively. RESULTS: Univariate analysis showed around 20 parameters of interest, 14 of which were statistically significant at a 0.05 level of significance. Logistic regression analysis identified 11 predictors of interest that were statistically significant. Tomato, coffee and canned meat consumption were associated with lower likelihood of breast cancer (OR = 0.988, 0.901, 0.892, respectively), whereas beans and cabbage consumption and low sodium salt were positively associated with breast cancer (OR = 1.045, 1.834, 1.028, respectively). Premenopausal status was associated with a lower risk of breast cancer compared to postmenopausal status (OR = 0.067). Not having experienced myocardial infarction was associated with lower odds of breast cancer (OR = 0.331). Increased height was also found to have a strong association with risk of breast cancer, with the odds of having breast cancer increasing for every centimetre increase in height (OR = 1.048). In terms of quantity, odds of having breast cancer were lower in those exposed to sunlight (OR = 0.891). The odds of having breast cancer were also lower in those not using the oral contraceptive pill (OR = 0.454). CONCLUSIONS: Various factors in this exploratory study were found to be associated with development of breast cancer. While causal conclusions cannot be made, tomato consumption is of particular interest, as these results corroborate findings found in other studies. A negative association of breast cancer with sunlight exposure and oral contraceptive pill use corroborates findings in other studies. Other associations with dietary intake can be explained by dietary changes. More robust studies in this area, including possible longitudinal studies, are warranted. PMID- 27679671 TI - Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina. AB - Targeting the photosensitive ion channel channelrhodopsin-2 (ChR2) to the retinal circuitry downstream of photoreceptors holds promise in treating vision loss caused by retinal degeneration. However, the high intensity of blue light necessary to activate channelrhodopsin-2 exceeds the safety threshold of retinal illumination because of its strong potential to induce photochemical damage. In contrast, the damage potential of red-shifted light is vastly lower than that of blue light. Here, we show that a red-shifted channelrhodopsin (ReaChR), delivered by AAV injections in blind rd1 mice, enables restoration of light responses at the retinal, cortical, and behavioral levels, using orange light at intensities below the safety threshold for the human retina. We further show that postmortem macaque retinae infected with AAV-ReaChR can respond with spike trains to orange light at safe intensities. Finally, to directly address the question of translatability to human subjects, we demonstrate for the first time, AAV- and lentivirus-mediated optogenetic spike responses in ganglion cells of the postmortem human retina. PMID- 27679673 TI - Validity of self-reported exposure to shift work. AB - OBJECTIVE: To evaluate the validity of widely used questionnaire items on work schedule using objective registry data as reference. METHOD: A cohort study of hospital employees who responded to a self-administered questionnaire on work schedule in 2008, 2012 and 2014 and were linked to individual-level pay-roll based records on work shifts. For predictive validity, leisure-time fatigue was assessed. RESULTS: According to the survey data in 2014 (n=8896), 55% of the day workers had at least 1 year of earlier shift work experience. 8% of the night shift workers changed to day work during the follow-up. Using pay-roll data as reference, questions on 'shift work with night shifts' and 'permanent night work' showed high sensitivity (96% and 90%) and specificity (92% and 97%). Self reported 'regular day work' showed moderate sensitivity (73%), but high specificity (99%) and 'shift work without night shifts' showed low sensitivity (62%) and moderate specificity (87%). In multivariate logistic regression analysis, the age-adjusted, sex-adjusted and baseline fatigue-adjusted association between 'shift work without night shifts' and leisure-time fatigue was lower for self-reported compared with objective assessment (1.30, 95% CI 0.94 to 1.82, n=1707 vs 1.89, 95% CI 1.06 to 3.39, n=1627). In contrast, shift work with night shifts, compared with permanent day work, was similarly associated with fatigue in the two assessments (2.04, 95% CI 1.62 to 2.57, n=2311 vs 1.82, 95% CI 1.28 to 2.58, n=1804). CONCLUSIONS: The validity of self-reported assessment of shift work varies between work schedules. Exposure misclassification in self-reported data may contribute to bias towards the null in shift work without night shifts. PMID- 27679674 TI - Sick leave in workers with arm, neck and/or shoulder complaints; defining occurrence and discriminative trajectories over a 2-year time period. AB - OBJECTIVES: Impediments due to complaints of non-traumatic arm, neck and/or shoulder (CANS) during work often leads to consultation in primary care. This study examines the occurrence of sick leave among workers with new CANS, and evaluates sick leave trajectories and their characteristics. METHODS: This prospective 2-year cohort study included workers with a new CANS presenting in general practice. Participants filled out postal questionnaires on sick leave at 6-monthly intervals. Latent class growth mixture modelling was used to identify distinct trajectories of sick leave. Multinomial regression analyses identified characteristics of the subgroups. RESULTS: During follow-up, of the 533 participants 190 reported at least one episode of sick leave due to CANS. Three sick leave trajectories were distinguished: (1) 'low-risk' trajectory (n=366), with a constant low probability over time; (2) 'intermediate risk' trajectory, with a high probability at first consultation followed by a steep decrease in probability of sick leave (n=122); (3) 'high-risk' trajectory (n=45), with a constant high probability of sick leave. Compared to the 'low-risk' trajectory, the other trajectories were characterised by more functional limitations, less specific diagnoses, more work-related symptoms and low coworker support. Specific for the 'high-risk' subgroup were more recurrent symptoms, more musculoskeletal comorbidity, high score on somatisation and low score on job demands. CONCLUSIONS: Three trajectories of sick leave were distinguished, graded from favourable to unfavourable. Several complaint-related and work-related factors and somatisation contributed modestly to identify an unfavourable trajectory of sick leave when presenting in primary care with CANS. PMID- 27679675 TI - Effect of CYP3A4 genetic polymorphisms on the genotoxicity of 4,4'-methylene bis(2-chloroaniline)-exposed workers. AB - OBJECTIVES: We investigated the relationship between 4,4'-methylene-bis(2 chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4). METHODS: We divided the study population into an exposed group (n=44 with total urine MBOCA >=20 MUg/g creatinine) and a control group (n=47 with total urine MBOCA <20 MUg/g creatinine). Lymphocyte MN frequency (MNF) and micronucleated cell (MNC) frequency were measured by the cytokinesis-block MN assay method. MNF reported as the number of micronuclei in binucleated cells per 1000 cells, and MNC reported as the number of binucleated cells with the presence of MN per 1000 cells. CYP3A4 alleles were measured by PCR-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: The mean MNF (6.11 vs 4.46 MN/1000 cells, p<0.001) and MNC (5.75 vs 4.15 MN/1000 cells, p<0.001) in the exposed workers was significantly higher than that in the controls. The CYP3A4 polymorphism A/A+A/G influenced the difference in the mean MNF (5.97 vs 4.38 MN/1000 cells, p<0.001) and MNC (5.60 vs 4.15 MN/1000 cells, p<0.001) between the MBOCA-exposed and control groups. After adjusting risk factors, the MNF level in the MBOCA-exposed workers was 0.520 MN cells/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. Similarly, the MNC level in the MBOCA-exposed workers was 0.593 MN/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. However, the difference in adjusted MNF and MNC between the exposed and control groups was not significant for the CYP3A4 polymorphism with the G/G genotype. CONCLUSIONS: We recommend that lymphocytes MNF and MNC are good indicators to evaluate MBOCA genotoxicity. Individuals with the CYP3A4 polymorphism A/A and A/G genotypes appear to be more susceptible to MBOCA genotoxicity. PMID- 27679676 TI - Freestanding 3-D microvascular networks made of alginate hydrogel as a universal tool to create microchannels inside hydrogels. AB - The diffusion of molecules such as nutrients and oxygen through densely packed cells is impeded by blockage and consumption by cells, resulting in a limited depth of penetration. This has been a major hurdle to a bulk (3-D) culture. Great efforts have been made to develop methods for generating branched microchannels inside hydrogels to support mass exchange inside a bulk culture. These previous attempts faced a common obstacle: researchers tried to fabricate microchannels with gels already loaded with cells, but the fabrication procedures are often harmful to the embedded cells. Herein, we present a universal strategy to create microchannels in different types of hydrogels, which effectively avoids cell damage. This strategy is based on a freestanding alginate 3-D microvascular network prepared by in-situ generation of copper ions from a sacrificial copper template. This alginate network could be used as implants to create microchannels inside different types of hydrogels. This approach effectively addresses the issue of cell damage during microfabrication and made it possible to create microchannels inside different types of gels. The microvascular network produced with this method is (1) strong enough to allow handling, (2) biocompatible to allow cell culturing, and (3) appropriately permeable to allow diffusion of small molecules, while sufficiently dense to prevent blocking of channels when embedded in different types of gels. In addition, composite microtubules could be prepared by simply pre-loading other materials, e.g., particles and large biomolecules, in the hydrogel. Compared with other potential strategies to fabricate freestanding gel channel networks, our method is more rapid, low-cost and scalable due to parallel processing using an industrially mass-producible template. We demonstrated the use of such vascular networks in creating microchannels in different hydrogels and composite gels, as well as with a cell culture in a nutrition gradient based on microfluidic diffusion. In this way, the freestanding hydrogel vascular network we produced is a universal functional unit that can be embedded in different types of hydrogel; users will be able to adopt this strategy to achieve vascular mass exchange in the bulk culture without changing their current protocol. The method is readily implementable to applications in vascular tissue regeneration, drug discovery, 3-D culture, etc. PMID- 27679677 TI - Silk patterns made by direct femtosecond laser writing. AB - Silk patterns in a film of amorphous water-soluble fibroin are created by tailored exposure to femtosecond-laser pulses (1030 nm/230 fs) without the use of photo-initiators. This shows that amorphous silk can be used as a negative tone photo-resist. It is also shown that water insoluble crystalline silk films can be precisely ablated from a glass substrate achieving the patterns of crystalline silk gratings on a glass substrate. Bio-compatible/degradable silk can be laser structured to achieve conformational transformations as demonstrated by infrared spectroscopy. PMID- 27679678 TI - Geometrical control of ionic current rectification in a configurable nanofluidic diode. AB - Control of ionic current in a nanofluidic system and development of the elements analogous to electrical circuits have been the subject of theoretical and experimental investigations over the past decade. Here, we theoretically and experimentally explore a new technique for rectification of ionic current using asymmetric 2D nanochannels. These nanochannels have a rectangular cross section and a stepped structure consisting of a shallow and a deep side. Control of height and length of each side enables us to obtain optimum rectification at each ionic strength. A 1D model based on the Poisson-Nernst-Planck equation is derived and validated against the full 2D numerical solution, and a nondimensional concentration is presented as a function of nanochannel dimensions, surface charge, and the electrolyte concentration that summarizes the rectification behavior of such geometries. The rectification factor reaches a maximum at certain electrolyte concentration predicted by this nondimensional number and decays away from it. This method of fabrication and control of a nanofluidic diode does not require modification of the surface charge and facilitates the integration with lab-on-a-chip fluidic circuits. Experimental results obtained from the stepped nanochannels are in good agreement with the 1D theoretical model. PMID- 27679679 TI - Omalizumab: A useful tool for inducing tolerance to bee venom immunotherapy. PMID- 27679680 TI - Exercising control over bipolar disorder. AB - Following extensive research exercise has emerged as an effective treatment for major depressive disorder, and it is now a recognised therapy alongside other interventions. In contrast, there is a paucity of research examining the therapeutic effects of exercise for those with bipolar disorder. Given that dysfunctional reward processing is central to bipolar disorder, research suggests that exercise can perhaps be framed as a reward-related event that may have the potential to precipitate a manic episode. The behavioural activation system (BAS) is a neurobehavioural system that is associated with responding to reward and provides an appropriate framework to theoretically examine and better understand the effects of exercise treatment on bipolar disorder. This article discusses recent research findings and provides an overview of the extant literature related to the neurobiological underpinnings of BAS and exercise as they relate to bipolar disorder. This is important clinically because depending on mood state in bipolar disorder, we postulate that exercise could be either beneficial or deleterious with positive or negative effects on the illness. Clearly, this complicates the evaluation of exercise as a potential treatment in terms of identifying its optimal characteristics in this population. PMID- 27679681 TI - Tiotropium in asthma: what is the evidence and how does it fit in? AB - Despite current therapeutic approaches asthma remains uncontrolled in a significant proportion of patients. Short-acting anticholinergic bronchodilators have a very long history of use in asthma, and recent data confirms the importance of acetylcholine as both a bronchoconstrictor and as a regulator of inflammation and remodeling in the lungs. Data from a comprehensive clinical trial programme, as well as use in primary care, show the efficacy and safety of tiotropium in adults with mild to moderate asthma when it is added to ICS and in severe asthma when it is added to high doses of ICS plus LABA, as well as in adolescents. Tiotropium is cost effective and its benefits are not restricted to particular phenotypes, making it a useful addition to the therapeutic options recommended by the Global Initiative for Asthma (GINA) for people with poorly controlled asthma at steps 4 & 5. PMID- 27679682 TI - International Consensus (ICON): allergic reactions to vaccines. AB - BACKGROUND: Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. METHODS: Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. RESULTS: Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. CONCLUSIONS: This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines. PMID- 27679684 TI - Racial disparity in colorectal cancer: Gut microbiome and cancer stem cells. AB - Over the past two decades there has been remarkable progress in cancer diagnosis, treatment and screening. The basic mechanisms leading to pathogenesis of various types of cancers are also understood better and some patients, if diagnosed at a particular stage go on to lead a normal pre-diagnosis life. Despite these achievements, racial disparity in some cancers remains a mystery. The higher incidence, aggressiveness and mortality of breast, prostate and colorectal cancers (CRCs) in African-Americans as compared to Caucasian-Americans are now well documented. The polyp-carcinoma sequence in CRC and easy access to colonic epithelia or colonic epithelial cells through colonoscopy/colonic effluent provides the opportunity to study colonic stem cells early in course of natural history of the disease. With the advent of metagenomic sequencing, uncultivable organisms can now be identified in stool and their numbers correlated with the effects on colonic epithelia. It would be expected that these techniques would revolutionize our understanding of the racial disparity in CRC and pave a way for the same in other cancers as well. Unfortunately, this has not happened. Our understanding of the underlying factors responsible in African-Americans for higher incidence and mortality from colorectal carcinoma remains minimal. In this review, we aim to summarize the available data on role of microbiome and cancer stem cells in racial disparity in CRC. This will provide a platform for further research on this topic. PMID- 27679685 TI - Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases. AB - The gene encoding bone morphogenetic protein-7 (Bmp7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of Bmp7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of Bmp7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases. PMID- 27679683 TI - Immunomodulation by mesenchymal stem cells: Interplay between mesenchymal stem cells and regulatory lymphocytes. AB - Mesenchymal stem cells (MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T (Treg) and B (Breg) cells. The induction of Treg and Breg cells is of particular interest since Treg and Breg cells have significant roles in maintaining immune tolerance. Several mechanisms have been proposed regarding to the MSCs-mediated induction of Treg and Breg cells. Accordingly, MSCs induce regulatory lymphocytes through secretion of multiple pleiotropic cytokines, cell-to-cell contact with target cells and modulation of antigen-presenting cells. Here, we summarized how MSCs induce Treg and Breg cells to provoke immunosuppression. PMID- 27679687 TI - Diagnostic reliability of the third finger middle phalanx maturation (MPM) method in the identification of the mandibular growth peak. AB - Background/objectives: The use of the sole third finger middle phalanx for a maturational method has been proposed but not fully investigated. Herein, the diagnostic reliability of an improved five-stage third finger middle phalanx maturation (MPM) method in the identification of mandibular growth peak has been investigated. Subjects/methods: From the files of the Burlington Growth Study, 35 subjects (20 males, 15 females) with at least 7 annual lateral cephalograms taken from 9 to 16 years were included. Mandibular growth was defined as annual increments in condylion-gnathion (Co-Gn) distance. Subsequently, individual annual increments in Co-Gn were arranged according to annual age intervals, with the first and last intervals defined as 9-10 years and 14/15-16 years, respectively. A full diagnostic reliability analysis (including positive likelihood ratio) was performed to establish the diagnostic reliability of the MPM stage 2 (MPS2) in the identification of the imminent mandibular growth peak. Results: The MPS2 had a satisfactory accuracy in the identification of imminent mandibular growth peak with an overall positive likelihood ratio of 10.3. However, reliability showed noteworthy variability being greater and lower for younger and older age intervals, respectively. Limitations: Secular trend, limited sample size, and annual recording in conjunction with the use of a discrete staging system. At the 15 years recording, 28 of 35 cases were missing. Conclusions/implications: The MPS2 and MPS3 may be considered associated with the onset and maximum mandibular growth peak, respectively, in most of the subjects, indicating their use in planning treatment timing. PMID- 27679686 TI - Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease. AB - Mesenchymal stem cells (MSCs) have been used to treat patients suffering from acute myocardial infarction (AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microRNAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease (CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD. PMID- 27679688 TI - Diagnostic Accuracy of Coronary Calcium Score Less than 100 in Excluding Coronary Artery Disease. AB - BACKGROUND: Coronary artery calcium score (CACS) is a quantitative assessment of calcifications and an established predictor of cardiovascular events. OBJECTIVES: In this study, we evaluated the diagnostic accuracy, negative predictive value (NPV), positive predictive value (PPV), specificity and sensitivity of CACS less than 100 in predicting significant coronary artery stenosis in patients with risk of coronary artery disease (CAD) in a vessel-based analysis. PATIENTS AND METHODS: A cross sectional study was carried out on a study population of 2527 consecutive stable patients with symptoms suggestive of CAD who were referred for coronary computed tomographic angiography (CCTA). We performed 1343 studies with 256 slice machine in Shahid Rajaee hospital and the other studies were carried out with 64 slice machine in Imam Khomeini hospital and the calcium score was quantified according to the Agatston method. RESULTS: At the cutoff point of 100 for coronary calcium scoring, there was high specificity (87%), high sensitivity (79%), high efficiency (84%), high PPV (79%), and high NPV (87%) in the diagnosis of significant stenosis in the whole heart. The frequency of zero calcium scoring was 59% in normal or nonsignificant stenosis and 7.6% in significant stenosis in the whole heart. Calcium scoring increased with greater severity of the arterial stenosis (P values < 0.001). CONCLUSION: We conclude that coronary calcium scoring provided useful information in the management of patients. In CACS less than 100, it has a NPV of 87% in excluding significant stenosis in patients with the risk of CAD but it does not have enough diagnostic accuracy for surely excluding coronary stenosis, so we should perform a combination of CACS and coronary CT angiography for patients. PMID- 27679689 TI - Imaging and Clinical Data of Placental Site Trophoblastic Tumor: A Case Report. AB - Placental site trophoblastic tumor (PSTT) is a very rare variant of gestational trophoblastic tumor. It can occur after normal termination of pregnancy or spontaneous abortion and ectopic or molar pregnancy. There is a wide range of clinical manifestations from a benign condition to an aggressive disease with fatal outcome. One of the most important characteristics of PSTT, unlike other forms of gestational trophoblastic diseases (GTD) is the presence of low beta subunit of human chorionic gonadotropin (beta-hCG) levels because it is a neoplastic proliferation of intermediate trophoblastic cells. However, human placental lactogen (hPL) is increased on histologic section and in the serum of patients too. We present a case of PSTT and discuss the differential diagnosis in order to further familiarize physicians with the diagnosis and treatment of this disease. It has a varied clinical spectrum and usually presents with irregular vaginal bleeding or amenorrhea. Diagnosis is confirmed by dilatation and curettage (D and C) and hysterectomy. Because chemotherapy is not effective, surgery is the cornerstone of treatment. This case is presented because it is a rare neoplasm with different treatments and it should be differentiated from molar pregnancy. PMID- 27679691 TI - Orbital Metastasis from Breast Cancer Without Significant Changes in CT Scan and MRI. PMID- 27679690 TI - Magnetic Resonance Angiography in the Diagnosis of Cerebral Arteriovenous Malformation and Dural Arteriovenous Fistulas: Comparison of Time-Resolved Magnetic Resonance Angiography and Three Dimensional Time-of-Flight Magnetic Resonance Angiography. AB - BACKGROUND: Traditional digital subtraction angiography (DSA) is currently the gold standard diagnostic method for the diagnosis and evaluation of cerebral arteriovenous malformation (AVM) and dural arteriovenous fistulas (dAVF). OBJECTIVES: The aim of this study was to analyze different less invasive magnetic resonance angiography (MRA) images, time-resolved MRA (TR-MRA) and three dimensional time-of-flight MRA (3D TOF MRA) to identify their diagnostic accuracy and to determine which approach is most similar to DSA. PATIENTS AND METHODS: A total of 41 patients with AVM and dAVF at their initial evaluation or follow-up after treatment were recruited in this study. We applied time-resolved angiography using keyhole (4D-TRAK) MRA to perform TR-MRA and 3D TOF MRA examinations simultaneously followed by DSA, which was considered as a standard reference. Two experienced neuroradiologists reviewed the images to compare the diagnostic accuracy, arterial feeder and venous drainage between these two MRA images. Inter-observer agreement for different MRA images was assessed by Kappa coefficient and the differences of diagnostic accuracy between MRA images were evaluated by the Wilcoxon rank sum test. RESULTS: Almost all vascular lesions (92.68%) were correctly diagnosed using 4D-TRAK MRA. However, 3D TOF MRA only diagnosed 26 patients (63.41%) accurately. There were statistically significant differences regarding lesion diagnostic accuracy (P = 0.008) and venous drainage identification (P < 0.0001) between 4D-TRAK MRA and 3D TOF MRA. The results indicate that 4D-TRAK MRA is superior to 3D TOF MRA in the assessment of lesions. CONCLUSION: Compared with 3D TOF MRA, 4D-TRAK MRA proved to be a more reliable screening modality and follow-up method for the diagnosis of cerebral AVM and dAVF. PMID- 27679693 TI - Split-Bolus Multidetector-Row Computed Tomography Technique for Characterization of Focal Liver Lesions in Oncologic Patients. AB - BACKGROUND: In oncologic patients, the liver is the most common target for metastases. An accurate detection and characterization of focal liver lesions in patients with known primary extrahepatic malignancy are essential to define management and prognosis. OBJECTIVES: To assess the diagnostic accuracy of the split-bolus multidetector-row computed tomography (MDCT) protocol in the characterization of focal liver lesions in oncologic patients. PATIENTS AND METHODS: We retrospectively analyzed the follow-up split-bolus 64-detector row CT protocol in 36 oncologic patients to characterize focal liver lesions. The split bolus MDCT protocol by intravenous injection of two boluses of contrast medium combines the hepatic arterial phase (HAP) and hepatic enhancement during the portal venous phase (PVP) in a single-pass. RESULTS: The split-bolus MDCT protocol detected 208 lesions and characterized 186 (89.4%) of them: typical hemangiomas (n = 9), atypical hemangiomas (n = 3), cysts (n = 78), hypovascular (n = 93) and hypervascular (n = 3) metastases. Twenty two (10.6%) hypodense lesions were categorized as indeterminate (<=5 mm). The mean radiation dose was 24.5+/-6.5 millisieverts (mSv). CONCLUSION: The designed split-bolus MDCT technique can be proposed alternatively to triphasic MDCT and in a single-pass to PVP in the initial staging and in the follow-up respectively in oncologic patients. PMID- 27679692 TI - User Acceptance of Picture Archiving and Communication System in the Emergency Department. AB - BACKGROUND: Picture archiving and communication system (PACS) has allowed the medical images to be transmitted, stored, retrieved, and displayed in different locations of a hospital or health system. Using PACS in the emergency department will eventually result in improved efficiency and patient care. In spite of the abundant benefits of employing PACS, there are some challenges in implementing this technology like users' resistance to accept the technology, which has a critical role in PACS success. OBJECTIVES: In this study, we will assess and compare user acceptance of PACS in the emergency departments of three different hospitals and investigate the effect of socio-demographic factors on this acceptance. MATERIALS AND METHODS: A variant of technology acceptance model (TAM) has been used in order to measure the acceptance level of PACS in the emergency department of three educational hospitals in Iran. A previously used questionnaire was validated and utilized to collect the study data. A stepwise multiple regression model was used to predict factors influencing acceptance score as the dependent variable. RESULTS: Mean age of participants was 32.9 years (standard deviation [SD] = 6.08). Participants with the specialty degree got a higher acceptance score than the three other groups (Mean +/- SD = 4.17 +/- 0.20). Age, gender, degree of PACS usage and participant's occupation (profession) did not influence the acceptance score. In our multiple regression model, all three variables of perceived usefulness (PU), perceived ease of use (PEU) and the effect of PACS (change) had a significant effect in the prediction of acceptance. The most influencing factor was change with the beta of 0.22 (P value < 0.001). CONCLUSION: PACS is highly accepted in all three emergency departments especially among specialists. PU, PEU and change are factors influencing PACS acceptance. Our study can be used as an evidence of PACS acceptance in emergency wards. PMID- 27679695 TI - Giant Lipomatosis of the Sciatic Nerve: Unique Magnetic Resonance Imaging Findings. AB - Lipomatosis of the nerve, also known as fibrolipomatous hamartoma, is characterized by the infiltration of the nerve by fibro-fatty tissue. The affected nerve becomes thicker, and it simulates a mass lesion. Lipomatosis usually affects the median nerve and lipomatosis of the sciatic nerve is extremely rare. Magnetic resonance imaging (MRI) is the key to diagnosis, and it is usually pathognomonic. In this report, MRI and diffusion-weighted MRI findings of a case of a giant sciatic nerve lipomatosis without macrodactyly are presented. The MRI findings are unique, and awareness of the MRI features of this rare soft tissue mass may prevent unnecessary biopsies and surgeries. PMID- 27679694 TI - Depth of Pleural Effusion in Thoracentesis: Comparison of Lateral, Posterolateral and Posterior Approaches in the Supine Position. AB - BACKGROUND: In patients who have difficulty sitting, thoracentesis is attempted in a supine position via lateral approach. Recently, a new table has been designed for supine thoracentesis. This table has gaps that allow access to the posterolateral and posterior hemithorax. OBJECTIVES: To compare important safety related parameters between lateral, posterolateral, and posterior approaches in supine thoracentesis. MATERIALS AND METHODS: First, two cadavers were placed supine on a table featuring gaps allowing access to the posterolateral and posterior hemithorax. Water was administered with sonographic measurement of the depth of pleural effusion (DPE) at the mid-axillary and posterior axillary line. Second, CT images were analyzed in 25 consecutive patients (32 free-shifting, moderate-to-large effusions; mean, 668 (146 - 2020 mL). DPE, craniocaudal distance that effusion can be visualized (CCD), and presence of passive atelectasis at each of the lateral, posterolateral, and posterior routes was assessed. RESULTS: In each cadaver, DPE in the posterolateral route was greater than that in the lateral route (P = 0.002, P < 0.001). The amount of pleural fluid enough to spread DPE to higher than 1 cm at the posterior axillary line was less than half the amount at the mid-axillary line (500 mL vs. 1,100 mL; 800 mL vs. 1700 mL). CT showed that the DPEs and CCDs of posterolateral and posterior routes were greater than those of the lateral route (P < 0.001). In thirteen effusions (40.6%), DPE was greater than 1 cm in both posterolateral and posterior routes but less than 1 cm in the lateral route. Frequencies of passive atelectasis in posterolateral and posterior routes (81.3% and 90.6%) were higher (P < 0.001) than that in the lateral route (28.1%). CONCLUSION: Safety-related parameters of posterolateral and posterior approaches in supine thoracentesis are far better than that of the conventional lateral approach. PMID- 27679696 TI - Histopathological Evaluation of the Effectiveness of Glycyrrhizic Acid as a Radioprotector Against the Development of Radiation-Induced Lung Fibrosis. AB - BACKGROUND: Radiotherapy of the thorax often causes lung inflammation leading to fibrosis. OBJECTIVES: The aim of this study was to investigate whether the use of glycyrrhizic acid (GLA) could improve the development of lung fibrosis in irradiated animals. MATERIALS AND METHODS: Wistar rats were divided into four groups. Group A rats received thoracic irradiation. Rats in group B received GLA and irradiation. Group C received GLA and no irradiation. Group D received no GLA and irradiation. GLA was administered at a dose of 4 mg/kg body weight using an intraperitoneal injection one hour before thoracic irradiation. Radiation therapy was delivered on a Cobalt-60 unit using a single fraction of 16 Gy. The animals were sacrificed at 32 weeks following thoracic irradiation. The lungs were dissected and blind histopathological evaluation was performed. RESULTS: Histopathologically, a decrease (statistically not significant) in the thickening of alveolar or bronchial wall, formation of fibrous bands, and superimposed collagen were noted in the animals in group B as compared to the animals in group A. CONCLUSION: In this experimental study, administration of GLA one hour before thoracic irradiation may be a protective agent against radiation-induced fibrosis in animals and this model could be used in future studies. PMID- 27679697 TI - Diffusion Weighted Imaging in Acute Attacks of Multiple Sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is one of the most common autoimmune disorders of the central nervous system. In spite of various imaging modalities, the definitive diagnosis of MS remains challenging. OBJECTIVES: This study was designed to evaluate the usefulness of diffusion weighted imaging (DWI) in the diagnosis of acute MS attack and to compare its results with contrast enhanced MRI (CE-MRI). PATIENTS AND METHODS: In this cross sectional study, seventy patients with definite diagnosis of relapsing-remitting MS were included. CE-MRI using 0.1 mmol/kg gadolinium as well as DWI sequences were performed for all patients. The percentage of patients with positive DWI was compared with the results of CE-MRI and the consistency between the two imaging modalities was evaluated. Moreover, the relationship between the time of onset of patient's symptoms and test results for both methods were investigated. RESULTS: CE-MRI yielded positive results for 61 (87%) patients and DWI yielded positive for 53 (76%) patients. In fifty patients (71.42%), both tests were positive and in six cases (8.57%), both were negative. The test results of three patients turned out to be positive in DWI, while they tested negative in CE-MRI. There was no significant relationship between the results of CE-MRI as well as DWI and the time of imaging from the onset of symptoms. CONCLUSION: These data indicate that while CE-MRI will depict more positive results, there are cases in which DWI will show a positive result while CE-MRI is negative. We suggest that the combination of these two imaging modalities might yield more positive results in diagnosing acute MS attack giving rise to a more accurate diagnosis. PMID- 27679699 TI - A Molecular Approach to Nested RT-PCR Using a New Set of Primers for the Detection of the Human Immunodeficiency Virus Protease Gene. AB - BACKGROUND: The human immunodeficiency virus (HIV-1) is the etiologic agent of AIDS. The disease can be transmitted via blood in the window period prior to the development of antibodies to the disease. Thus, an appropriate method for the detection of HIV-1 during this window period is very important. OBJECTIVES: This descriptive study proposes a sensitive, efficient, inexpensive, and easy method to detect HIV-1. PATIENTS AND METHODS: In this study 25 serum samples of patients under treatment and also 10 positive and 10 negative control samples were studied. Twenty-five blood samples were obtained from HIV-1-infected individuals who were receiving treatment at the acquired immune deficiency syndrome (AIDS) research center of Imam Khomeini hospital in Tehran. The identification of HIV-1 positive samples was done by using reverse transcription to produce copy deoxyribonucleic acid (cDNA) and then optimizing the nested polymerase chain reaction (PCR) method. Two pairs of primers were then designed specifically for the protease gene fragment of the nested real time-PCR (RT-PCR) samples. Electrophoresis was used to examine the PCR products. The results were analyzed using statistical tests, including Fisher's exact test, and SPSS17 software. RESULTS: The 325 bp band of the protease gene was observed in all the positive control samples and in none of the negative control samples. The proposed method correctly identified HIV-1 in 23 of the 25 samples. CONCLUSIONS: These results suggest that, in comparison with viral cultures, antibody detection by enzyme linked immunosorbent assay (ELISAs), and conventional PCR methods, the proposed method has high sensitivity and specificity for the detection of HIV-1. PMID- 27679698 TI - Diagnostic Accuracy of Dual-Source Computerized Tomography Coronary Angiography in Symptomatic Patients Presenting to a Referral Cardiovascular Center During Daily Clinical Practice. AB - BACKGROUND: There are numerous studies that address the diagnostic value of dual source computed tomography (DSCT) as an alternative to conventional coronary angiography (CCA). However, the benefit of application of DSCT in a real world clinical setting should be evaluated. OBJECTIVES: To determine the diagnostic accuracy of DSCT technique compared with CCA as the gold standard method in detection of coronary artery stenosis among symptomatic patients who are presented to a referral cardiovascular center during daily clinical practice. PATIENTS AND METHODS: Evaluating the medical records of a tertiary care referral cardiovascular center, 47 patients who had undergone DSCT and CCA, and also met the inclusion and exclusion criteria of the study were selected. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) of the DSCT imaging technique were calculated. RESULTS: In total, 97.8% of the segments (628/642) could be visualized with diagnostic image quality via DSCT coronary angiography. The mean heart rate during DSCT was 69.2 +/- 12.2 bpm (range: 39 - 83 bpm), and the mean Agatston score was 507.7 +/- 590.5 (range: 0 - 2328). Per segment analysis of the findings revealed that the sensitivity, specificity, PPV, NPV, positive LR (PLR) and negative LR (NLR) of DSCT technique for evaluation of patients with coronary artery disease were 93.7%, 96.8%, 92.7%, 97.2%, 29.4, and 0.066, respectively. Also per vessel, analysis of the findings showed a sensitivity of 97.1%, a specificity of 94.0%, PPV of 95.3%, NPV of 96.3%, PLR of 16.1, and NLR of 0.030. CONCLUSION: Our results indicate that DSCT coronary angiography provides high diagnostic accuracy for the evaluation of CAD patients during daily routine practice of a referral cardiovascular setting. PMID- 27679700 TI - Anti-Listerial Activity of Four Seaweed Essential Oils Against Listeria monocytogenes. AB - BACKGROUND: Listeria monocytogenes is one of the most virulent types of bacteria and causes severe foodborne illness, such as listeriosis. Because this pathogen has become resistant to sanitizers and other disinfectants that are used to clean utensils and surfaces during food processing, it poses a serious threat to the food industry. OBJECTIVES: The study was conducted to determine the anti listerial potential of essential oils extracted from four edible seaweeds against L. monocytogenes. MATERIALS AND METHODS: Essential oil was extracted from four edible seaweeds (Enteromorpha linza, Undaria pinnatifida, Laminaria japonica, and Porphyra tenera) against L. monocytogenes using the microwave hydrodistillation method. The anti-listerial activity of the essential oil was determined using the standard disc diffusion method. RESULTS: Among the four essential oils, E. linza (ELEO) was most effective against all three strains of L. monocytogenes (11.3 - 16.0 mm). The other three essential oils were only effective against two strains, L. monocytogenes ATCC 19115 (10.0 - 10.5 mm) and L. monocytogenes ATCC 7644 (11.0 - 15.0 mm). The minimum inhibitory concentration and the minimum bactericidal concentration of all four essential oils varied from 12.5 - 25.0 mg/mL. Further, the mode of action of ELEO against L. monocytogenes was investigated by examining its effect on cell viability, the release of 260-nm absorbing materials, the number of K+ ions, the relative electrical conductivity, and the salt tolerance capacity. The results indicated that the essential oils exhibited strong anti listerial activity against multiple strains of L. monocytogenes. It displayed potential inhibitory effects on the viability of bacterial cells and loss of integrity as indicated by an increase in the relative electrical conductivity, leakage of K+ ions and other 260-nm absorbing materials, and a loss of the salt tolerance capacity. CONCLUSIONS: The results presented herein provided insight into a possible explanation for the modes of action of essential oils on L. monocytogenes. The outcome of the present study may aid the food industry in locating the most promising potential anti-listerial agents from edible seaweed sources to control L. monocytogenes and also in facilitating their application in food processing and preservation techniques in a nontoxic and environmental friendly manner. PMID- 27679701 TI - PCR Based Detection of Phase Variable Genes in Pakistani Based Clinical Helicobacter pylori Strains. AB - BACKGROUND: The distribution pattern of phase-variable genes varies from strain to strain and from region to region. The present study was carried out to investigate the distribution pattern of phase-variable genes within Pakistan based Helicobacter pylori strains and to analyze and compare them with strains prevalent in other parts of the world. OBJECTIVES: To determine the distribution pattern of phase-variable genes in H. pylori strains circulating in Pakistan. PATIENTS AND METHODS: Biopsy samples were collected from 85 symptomatic patients suffering from various upper gastrointestinal tract symptoms. The biopsy specimens were chopped, then inoculated on H. pylori-specific media and incubated in a Campylobacter Gas Generating kit. Positive isolates were further confirmed via staining and biochemical procedures. Primers were designed for five phase variable genes using OligoCalc, an oligonucleotide properties calculator (version 3.26) according to parameters stipulated in the literature. Polymerase chain reaction (PCR) was performed on all positive isolates to determine the presence or absence of phase-variable genes. RESULTS: On culturing, the prevalence of H. pylori infections in the samples was 44.7%. The prevalence was higher in females than in males, and it increased with age. PCR amplification revealed that the hsdR gene was present in 79% of samples, while the mod and beta-subunit genes were present in 16% and 30% of samples, respectively. The streptococcal M protein gene was found in 79%, while the fliP gene was prevalent in 56%. CONCLUSIONS: The distribution patterns of phase-variable genes in Pakistani H. pylori strains were found to be somewhat different. The dominant prevalence of the hsdR gene was an interesting finding, considering its role in bacterial defense in both micro- and macroenvironments. PMID- 27679702 TI - Aflatoxins in Food Products in Iran: a Review of the Literature. AB - CONTEXT: Mycotoxins are secondary metabolites produced by certain toxigenic fungi and the most of them are aflatoxins, fumonisins, trichothecenes, ochratoxin A, patulin, and zearalenone. EVIDENCE ACQUISITION: In consideration of the consumption of certain farm products for animal feed and the prevalence of toxigenic fungi and mycotoxins in food, the present study was performed to evaluate this situation in Iran with a review of the literature using search engines. All published articles were selected using Iran Medex, Magiran, PubMed NCBI, and Google Scholar. RESULTS: Aflatoxins have been found in many food products in Iran. CONCLUSIONS: It is necessary to detect aflatoxins in foods and food products as early as possible, before they enter human or animal bodies. There is a high consumption of milk and dairy products in Iran, and the proper management of animal foods can help to decrease the aflatoxins in milk. PMID- 27679703 TI - Microdilution in vitro Antifungal Susceptibility Patterns of Candida Species, From Mild Cutaneous to Bloodstream Infections. AB - BACKGROUND: Candida species, as opportunistic organisms, can cause various clinical manifestations, ranging from mild cutaneous infections to systemic candidiasis in otherwise healthy individuals. Remarkably, the incidence and mortality rates of candidemia have significantly increased worldwide, even after advances in medical interventions and the development of novel antifungal drugs. OBJECTIVES: Given the possible resistance to antifungal agents, susceptibility testing can be useful in defining the activity spectrum of antifungals and determining the appropriate treatment regime. MATERIALS AND METHODS: The in vitro susceptibilities of molecularly identified Candida strains (n = 150) belonging to seven species recovered from clinical specimens, including vaginal, cutaneous, sputum, bronchoalveolar lavage (BAL), and blood samples, were determined for six antifungal drugs (amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin), based on the clinical and laboratory standards institute's M27-A3 and M27-S4 documents. RESULTS: Candida albicans was the most frequently isolated species (44.66%), followed by non-albicans Candida, including C. glabrata (20%), C. parapsilosis (13.33%), C. krusei (8%), C. tropicalis (7.3%), C. dubliniensis (4%), and C. africana (3.33%). Posaconazole had the lowest geometric mean minimum inhibitory concentration (MIC) (0.0122 ug/ml), followed by amphotericin B (0.0217 ug/mL), voriconazole (0.1022 ug/mL), itraconazole (0.1612 ug/mL), caspofungin (0.2525 ug/mL), and fluconazole (0.4874 ug/mL) against all isolated Candida species. Candida africana and C. parapsilosis were significantly more susceptible to fluconazole, compared to C. albicans and other Candida species (P < 0.001). However, their clinical effectiveness in the treatment of Candida infections remains to be determined. CONCLUSIONS: These findings highlight the importance of precise and correct species identification of clinical yeast isolates via molecular approaches, and of monitoring the antifungal susceptibility of Candida species recovered from clinical sources. Laboratories should consider routine MIC testing of C. glabrata isolates collected from sterile sites. Surveillance studies of Candida species and new analyses of antifungal treatment outcomes will allow more informed determinations of the value of these drugs in the antifungal armamentarium. PMID- 27679704 TI - Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis. AB - BACKGROUND: Whooping cough is caused by Bordetella pertussis, and it remains a public health concern. Whole-cell pertussis vaccines have been commonly employed for expanded immunization. There is no doubt of the efficacy of whole cell pertussis vaccine, but it is necessary to improve the vaccine to decrease its toxicity. OBJECTIVES: In this study, an inactivation process of dealing with pertussis bacteria is optimized in order to decrease the bacteria content in human doses of vaccines and reduce the vaccine's toxicity. MATERIALS AND METHODS: The bacterial suspensions of pertussis strains 509 and 134 were divided into 21 sample parts from F1 to F21 and inactivated under different conditions. The inactivated suspensions of both strains were tested for opacity, non-viability, agglutination, purity, and sterility; the same formulation samples that passed quality tests were then pooled together. The pool of inactivated suspensions were analyzed for sterility, agglutination, opacity, specific toxicity, and potency. RESULTS: The harvest of both bacterial strains showed purity. The opacity of various samples were lost under different treatment conditions by heat from 8% to 12%, formaldehyde 6% to 8%, glutaraldehyde 6% to 8%, and thimerosal 5% to 8%. Tests on suspensions after inactivation and on pooled suspensions showed inactivation conditions not degraded agglutinins of both strains. The samples of F2, F4, F8, F12, F15, and F17 passed the toxicity test. The potency (ED50) of these samples showed following order F17 > F12 > F8 > F15, F4 > F2, and F17 revealed higher potency compared to other formulations. CONCLUSIONS: It can be concluded that F17 showed desirable outcomes in the toxicity test and good immunogenicity with a low bacterial number content. Consequently, lower adverse effects and good immunogenicity are foreseeable for vaccine preparation with this method. PMID- 27679705 TI - Ralstonia mannitolilytica-Induced Septicemia and Homology Analysis in Infected Patients: 3 Case Reports. AB - BACKGROUND: Ralstonia mannitolilytica is an emerging opportunistic pathogen. Hospital outbreaks of Ralstonia spp. are mainly associated with contaminated treatment water or auxiliary instruments. OBJECTIVES: In this report, we summarize the clinical infection characteristics of R. mannitolilytica, the drug susceptibility testing of the bacterial strains, and the results of related infection investigations. PATIENTS AND METHODS: We retrospectively analyzed the clinical information of 3 patients with R. mannitolilytica. RESULTS: The patients' primary-onset symptoms were chills and fever. The disease progressed rapidly and septic shock symptoms developed. Laboratory tests indicated progressively decreased white blood cells and platelets, as well as significant increases in certain inflammation indicators. The effect of treatment with Tazocin was good. The growth period of R. mannitolilytica in sterile distilled water was > 6 months. The pulsed-field gel electrophoresis (PFGE) results revealed that the infectious strains from these 3 patients were not the same clonal strain. This bacterium was not detected in the nosocomial infection samples. CONCLUSIONS: Our results suggest that R. mannitolilytica-induced septicemia had an acute disease onset and rapid progression. The preferred empirical antibiotic was Tazocin. In these 3 cases, the R. mannitolilytica induced septicemia was not due to clonal transmission. PMID- 27679706 TI - Spa Typing of Staphylococcus aureus Strains Isolated From Clinical Specimens of Patients With Nosocomial Infections in Tehran, Iran. AB - BACKGROUND: The incidence of nosocomial Staphylococcus aureus infection is increasing annually and becoming a true global challenge. The pattern of Staphylococcus aureus protein A (spa) types in different geographic regions is diverse. OBJECTIVES: This study determined the prevalence of methicillin resistant S. aureus and different spa types in S. aureus clinical isolates. MATERIALS AND METHODS: During a six-month period, 90 S. aureus isolates were recovered from 320 clinical specimens. The in vitro susceptibility of various S. aureus isolates to 16 antibiotic discs was assessed using the Kirby-Bauer disk diffusion method. Molecular typing was carried out with S. aureus protein A typing via polymerase chain reaction. RESULTS: The frequency of methicillin resistant S. aureus in our study was 88.9%. Twenty-three (25.5%) isolates were positive for panton-valentine leukocidin encoding genes. S. aureus presented a high resistance rate to ampicillin (100%) and penicillin (100%). No resistance was observed to vancomycin, teicoplanin, or linezolid. The rates of resistance to the majority of antibiotics tested varied between 23.3% and 82.2%. The rate of multidrug resistance among these clinical isolates was 93.3%. The 90 S. aureus isolates were classified into five S. aureus protein A types: t037 (33.3%), t030 (22.2%), t790 (16.7%), t969 (11.1%), and t044 (7.7%). Eight (8.9%) isolates were not typable using the S. aureus protein A typing method. CONCLUSIONS: We report a high methicillin-resistant S. aureus rate in our hospital. Additionally, t030 and t037 were the predominant spa-types among hospital-associated S. aureus. Our findings emphasize the need for continuous surveillance to prevent the dissemination of multidrug resistance among different S. aureus protein A types in Iran. PMID- 27679707 TI - Prevalence of Cytomegalovirus in Patients With Multiple Sclerosis: A Case-Control Study in Northern Iran. AB - BACKGROUND: Multiple sclerosis (MS) is a chronic debilitating disease known as one of the most common neurological dysfunctions in young adults. Recent studies suggest that infections with herpesviruses play a critical role in the pathogenesis of MS. OBJECTIVES: The present investigation aimed to detect the presence of cytomegalovirus (CMV) in patients with MS using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) methods. PATIENTS AND METHODS: Plasma and peripheral blood mononuclear cells (PBMCs) were collected from MS patients (n = 82) and from blood donors as control group (n = 89). They were tested for the presence of CMV antibodies and DNA by ELISA and PCR, respectively. RESULTS: Anti-CMV was positive in 65 (79.3%) and 69 (77.5%) of the MS patients and healthy subjects, respectively (P= 0.853). Similarly, 23 (28%) and 2 (2.2%) patients were positive for CMV DNA among the MS and control groups, respectively. Statistical analysis showed that the frequency of CMV DNA in the MS patients was significantly higher than in the healthy controls (P < 0.001). CONCLUSIONS: The results of this study showed a possible association between CMV infection and MS. Further experimental and epidemiological studies using case control approaches are needed to confirm this association. PMID- 27679708 TI - The Prevalence of SEN Virus and Occult Hepatitis B (OBI) Virus Infection Among Blood Donors in Ahvaz City. AB - BACKGROUND: The SEN virus (SENV) is a prevalent blood borne pathogen that has a worldwide incidence. SENV is comprised of eight genotypes; genotypes H and D are frequently associated with the pathogenesis of non-A - E hepatitis and post transfusion hepatitis in blood donors and hepatitis patients. So far, no SENV pathogenesis has been reported in the liver biopsies of SENV carriers, but the frequency of SENV and its related genotypes requires further molecular epidemiology studies in different regions of the world. Occult hepatitis B infection (OBI) is another global public health problem that is primarily transmitted via blood transfusions. Therefore, the identification of OBI among blood donors is key to preventing the spread of this disease. The relationship between SENV and OBI requires further evaluation. OBJECTIVES: The aim of this study was to determine the prevalence of SENV-D and SENV-H in blood donors in Ahvaz city with a particular focus on co-infection with OBI. PATIENTS AND METHODS: This study had a cross-sectional design and included 184 healthy consecutive blood donors who visited a blood transfusion center in Ahvaz city from October-November 2013. The sera of all blood donors negative for HBsAg, anti HCV antibody, and anti-HIV antibody were tested for SENV-D and SENV-H using nested polymerase chain reaction (PCR). In addition, tests for HBV DNA (PCR), HBcIgG (ELISA), liver function (aspartate transaminase and alanine transaminase), and alkaline phosphatase were carried out. RESULTS: Liver function tests in the healthy blood donors were within the normal range. The incidence rates of SENV-D and SENV-H in the 184 total blood donors were 10 (5.4%) (95% confidence interval (CI): 2.1% - 9.0%) and 32 (17.4%) cases (95% CI: 12.0% - 23.0%), respectively. SENV-H/D co-infection occurred in 2 (1.1%) patients. The sera of 8/184 (4.3%) were positive for anti-HBc antibody but negative for HBV DNA. CONCLUSIONS: Regardless of the presence of nonpathogenic SENV, 44/184 (24%) blood donors tested positive for both SENV-D and SENV-H. Although 4.3% of blood donors were positive for HBcIgG but negative for HBV DNA, the presence of OBI cannot be ruled out unless their liver biopsies show negative for HBV DNA. PMID- 27679709 TI - Atypical anti-glomerular basement membrane disease: lessons learned. AB - Anti-glomerular basement membrane (GBM) disease usually pursues a self-limited course, at least from the immunological perspective. In addition, circulating antibodies to cryptic, conformational epitopes within the NC1 domain of the alpha 3 chain of Type IV Collagen are commonly found at the zenith of the clinical disease. However, exceptions to these general rules do occur, as exemplified by two remarkable cases reported in this issue of the Clinical Kidney Journal. The possible explanations for and the lessons learned from these uncommon occurrences are discussed in this short commentary. PMID- 27679710 TI - Multiple recurrences of anti-glomerular basement membrane disease with variable antibody detection: can the laboratory be trusted? AB - Anti-glomerular basement membrane (GBM) disease is commonly a monophasic illness. We present the case of multiple recurrences of anti-GBM disease with varying serum anti-GBM antibody findings. A 33-year-old female tobacco user presenting with hematuria was diagnosed with anti-GBM disease by renal biopsy. Five years later, she presented with alveolar hemorrhage and positive anti-GBM antibody. She presented a third time with alveolar hemorrhage but undetectable anti-GBM antibody. With each occurrence, symptoms resolved with plasmapheresis, intravenous methylprednisone and oral cyclophosphamide. The relationship between anti-GBM antibody findings and disease presentation is complex. Clinicians should be aware of the possibility of seronegative anti-GBM disease. PMID- 27679711 TI - Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time. AB - Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody-positive flares with pulmonary and renal involvement, and anti-GBM antibody-negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti GBM antibody status over time. Disease severity paralleled the detection of anti GBM antibodies but was independent of IgG subtype staining along the GBM. This case suggests a role for changing subpopulations of pathogenic antibodies as an explanation for variation in disease phenotype and anti-GBM antibody results. PMID- 27679712 TI - FGF23 in kidney transplant: the strange case of Doctor Jekyll and Mister Hyde. AB - During the last decade, a new view into the molecular mechanisms of chronic kidney disease-mineral bone disorder (CKD-MBD) has been proposed, with fibroblast growth factor 23 (FGF23) as a novel player in the field. Enhanced serum FGF23 levels cause a reduction in serum phosphate, together with calcitriol suppression and consequent hyperparathyroidism (HPT). In contrast, reduced serum FGF23 levels are associated with hyperphosphatemia, higher calcitriol levels and parathyroid hormone (PTH) suppression. In addition, serum FGF23 levels are greatly increased and positively correlated with serum phosphate levels in CKD patients. In this population, high serum FGF23 concentration seems to predict the occurrence of refractory secondary HPT and to be associated with higher mortality risk in incident haemodialysis patients. In living-donor kidney transplant recipients, a faster normalization of FGF23 and phosphate levels with a lower prevalence of HPT, may be considered a major pathway to investigate. PMID- 27679713 TI - FGF23 is associated with early post-transplant hypophosphataemia and normalizes faster than iPTH in living donor renal transplant recipients: a longitudinal follow-up study. AB - BACKGROUND: We aimed to longitudinally analyse changes in the levels of serum fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH) and associated minerals in patients undergoing renal transplantation. METHODS: Sixty three patients with end-stage renal disease (ESRD) who underwent living donor transplantation were recruited. Serum FGF23, iPTH, uric acid, inorganic phosphorous (iP), blood urea nitrogen and serum creatinine were measured pre transplant and at 1 (M1), 3 (M3) and 12 months (M12) post-transplantation. RESULTS: FGF23 levels were decreased at M1, M3 and M12 by 93.81, 96.74 and 97.53%, respectively. iPTH levels were decreased by 67.95, 74.95 and 84.9%, respectively. The prevalence of hyperparathyroidism at M1, M3 and M12 post transplantation was 63.5, 42.9 and 11.1%, respectively. FGF23 and iP levels remained above the normal range in 23 (36.5%) and 17 (27%) patients at M1, 10 (15.9%) and 5 (8%) at M3 and in none at M12 post-transplantation, respectively. A multivariate regression model revealed that, pre-transplant, iP was positively associated with iPTH (P = 0.016) but not with FGF 23; however, post-transplant, iP level was negatively associated with FGF23 (P < 0.001) but not with iPTH. CONCLUSIONS: Post-transplant FGF23 levels settle faster than those of iPTH. However, 11% of patients continued to have hyperparathyroidism even after 12 months. PMID- 27679714 TI - Serum FGF23 levels may not be associated with serum phosphate and 1,25 dihydroxyvitamin D levels in patients with Fanconi syndrome-induced hypophosphatemia. AB - Fibroblast growth factor 23 (FGF23) is regulated by sustained phosphate supplementation and restriction. However, few studies have investigated FGF23 levels in patients with Fanconi syndrome. Therefore, we evaluated intact and C terminal FGF23 and FGF23-associated parameters in four patients with Fanconi syndrome. Serum intact and C-terminal FGF23 levels were extremely low. Although serum phosphate and 1,25-dihydroxyvitamin D levels improved to or above the normal range within 1 year of treatment with oral phosphate and calcitriol, serum FGF23 levels remained low. Serum FGF23 levels in patients with Fanconi syndrome might be regulated by novel factors other than serum phosphate and 1,25 dihydroxyvitamin D levels. PMID- 27679716 TI - Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: Why to measure glomerular filtration rate with iohexol? AB - A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research. PMID- 27679717 TI - Cardiovascular-renal complications and the possible role of plasminogen activator inhibitor: a review. AB - Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin-angiotensin aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction. While the renin-angiotensin-aldosterone system and growth factors, such as transforming growth factor-beta (TGF-beta), are almost always part of the process, there are rare experimental observations of PAI-1 expression without their interaction. Here we review the literature on PAI-1 and its role in vascular, fibrotic and oxidative injury as well as work suggesting potential areas of intervention in the pathogenesis of multiple disorders. PMID- 27679715 TI - Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol? AB - While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method. PMID- 27679718 TI - Approach to atherosclerotic renovascular disease: 2016. AB - The management of atherosclerotic renal artery stenosis in patients with hypertension or impaired renal function remains a clinical dilemma. The current general consensus, supported by the results of the Angioplasty and Stenting for Renal Atherosclerotic Lesions and Cardiovascular Outcomes for Renal Artery Lesions trials, argues strongly against endovascular intervention in favor of optimal medical management. We discuss the limitations and implications of the contemporary clinical trials and present our approach and formulate clear recommendations to help with the management of patients with atherosclerotic narrowing of the renal artery. PMID- 27679719 TI - Comparison of trends in colorectal cancer screening in the US end-stage renal disease population and the US Medicare population. AB - BACKGROUND: Although patients treated with maintenance hemodialysis are at an increased risk of colorectal cancer compared with the general population, national practices for colorectal cancer screening have not been reported in this population. We assessed the performance of colorectal cancer screening in the US end-stage renal disease program in comparison with the US Medicare population. METHODS: We studied the United States Renal Data System for US prevalent hemodialysis patients between 2002 and 2011 who had Medicare as their primary insurer. We assessed procedure codes for performance of common colorectal cancer screening tests, including fecal occult blood testing, sigmoidoscopy and colonoscopy. We assessed screening sigmoidoscopy and screening colonoscopy only and excluded patients who had preexisting colon cancer or gastrointestinal hemorrhage. Because colorectal cancer screening recommendations are established for hemodialysis patients who have been listed for kidney transplantation, but no general recommendations exist for patients who are not wait-listed, we assessed colorectal cancer screening separately for the two groups. RESULTS: We found that 1-year performance of colonoscopy in wait-listed hemodialysis patients was similar to or higher than that in general Medicare patients of the same age, while performance of colonoscopy in non-wait-listed patients was significantly lower than among general Medicare patients of the same age. CONCLUSIONS: Given improved survival among hemodialysis patients in the last decade, the utility of colorectal cancer screening even among non-wait-listed hemodialysis patients should be reassessed. PMID- 27679720 TI - The impact of haemodialysis arteriovenous fistula on haemodynamic parameters of the cardiovascular system. AB - BACKGROUND: Satisfactory vascular access flow (Qa) of an arteriovenous fistula (AVF) is necessary for haemodialysis (HD) adequacy. The aim of the present study was to further our understanding of haemodynamic modifications of the cardiovascular system of HD patients associated with an AVF. The main objective was to calculate using real data in what way an AVF influences the load of the left ventricle (LLV). METHODS: All HD patients treated in our dialysis unit and bearing an AVF were enrolled into the present observational cross-sectional study. Fifty-six patients bore a lower arm AVF and 30 an upper arm AVF. Qa and cardiac output (CO) were measured by means of the ultrasound dilution Transonic Hemodialysis Monitor HD02. Mean arterial pressure (MAP) was calculated; total peripheral vascular resistance (TPVR) was calculated as MAP/CO; resistance of AVF (AR) and systemic vascular resistance (SVR) are connected in parallel and were respectively calculated as AR = MAP/Qa and SVR = MAP/(CO - Qa). LLV was calculated on the principle of a simple physical model: LLV (watt) = TPVR.CO(2). The latter was computationally divided into the part spent to run Qa through the AVF (LLVAVF) and that part ensuring the flow (CO - Qa) through the vascular system. The data from the 86 AVFs were analysed by categorizing them into lower and upper arm AVFs. RESULTS: Mean Qa, CO, MAP, TPVR, LLV and LLVAVF of the 86 AVFs were, respectively, 1.3 (0.6 SD) L/min, 6.3 (1.3) L/min, 92.7 (13.9) mmHg, 14.9 (3.9) mmHg.min/L, 1.3 (0.6) watt and 19.7 (3.1)% of LLV. A statistically significant increase of Qa, CO, LLV and LLVAVF and a statistically significant decrease of TPVR, AR and SVR of upper arm AVFs compared with lower arm AVFs was shown. A third-order polynomial regression model best fitted the relationship between Qa and LLV for the entire cohort (R (2) = 0.546; P < 0.0001) and for both lower (R (2) = 0.181; P < 0.01) and upper arm AVFs (R (2) = 0.663; P < 0.0001). LLVAVF calculated as % of LLV rose with increasing Qa according to a quadratic polynomial regression model, but only in lower arm AVFs. On the contrary, no statistically significant relationship was found between the two parameters in upper arm AVFs, even if mean LLVAVF was statistically significantly higher in upper arm AVFs (P < 0.0001). CONCLUSIONS: Our observational cross-sectional study describes statistically significant haemodynamic modifications of the CV system associated to an AVF. Moreover, a quadratic polynomial regression model best fits the relationship between LLVAVF and Qa, but only in lower arm AVFs. PMID- 27679721 TI - Cutaneous Mycobacterium chelonae infection distal to the arteriovenous fistula. AB - A few single cases of Mycobacterium chelonae skin infection have been reported in haemodialysis patients. We report three additional cases that share peculiar clinical characteristics, pointing to diagnostic clues. All three cases presented as erythematous nodules developing distally to a proximal arteriovenous fistula (AVF). This presentation was identical to that of two published cases. A survey of all Belgian haemodialysis units during the period 2007-11 yields an estimated incidence of ~0.9/10 000 patient-years. Although the source of M. chelonae remains unclear, this specific clinical presentation should be added to the listing of potential complications of an AVF and should be recognized, as it is fully treatable if diagnosed by culture and tissue biopsy. PMID- 27679723 TI - RENEW-a renal redesign project in predialysis patient care. AB - BACKGROUND: An ageing population and geographical growth, along with an increase in the number of people that reside in specific location, are increasing the demand for renal replacement therapies. Hospital-based haemodialysis units are struggling to cope with the associated physical, staffing and cost demands. Home based dialysis therapies are known to be more cost effective with superior social, physical health and survival outcomes. METHODS: 'RENEW, a renal redesign project, examined the pre-dialysis health care experience of renal patients to find opportunities to improve patient care outcomes and increase the uptake of home-based dialysis therapies. This article details two crucial parts of the approach to change management: (i) diagnostics-an inclusive, client focused, multidisciplinary approach to identify issues relating to the pre-dialysis journey-and (ii) solution design-an inclusive problem-solving approach to identify and marry solutions to the issues identified during diagnostics. RESULTS: Based on feedback from patients/caregivers and staff interviews, utilizing a clinical redesign methodology, a new model of care was developed, implemented and subsequently embedded into clinical practice. The results have been evident via improved care coordination, enhanced patient preparation for dialysis, improved patient psychosocial welfare and, importantly, an increased number of patients planned for and commencing home dialysis. This has empowered patients by giving them the confidence, knowledge and skills to be actively engaged in their own care. The project resulted in significant expenditure avoidance. CONCLUSION: Change management strategies with successful implementation are vital components of evolving clinical practice to achieve both clinical and organizational goals. PMID- 27679722 TI - FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease. AB - Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients. PMID- 27679724 TI - Applying effective teaching and learning techniques to nephrology education. AB - The interest in nephrology as a career has declined over the last several years. Some of the reasons cited for this decline include the complexity of the specialty, poor mentoring and inadequate teaching of nephrology from medical school through residency. The purpose of this article is to introduce the reader to advances in the science of adult learning, illustrate best teaching practices in medical education that can be extrapolated to nephrology and introduce the basic teaching methods that can be used on the wards, in clinics and in the classroom. PMID- 27679725 TI - Takotsubo cardiomyopathy with left ventricular thrombus presenting as critical limb ischaemia. AB - Takotsubo cardiomyopathy (TC) is a rare condition, characterized by acute left ventricular (LV) dysfunction in the absence of flow-limiting coronary artery disease, usually provoked by a physical or emotional stressor. The condition is far more common in women. The commonest presenting symptoms in patients with TC are chest pain and shortness of breath, often mimicking an acute coronary syndrome. A number of complications of TC are recognized, and very rarely patients experience cardioembolic phenomena secondary to LV thrombus formation in TC. We present the case of a 48-year-old lady presenting with peripheral limb ischaemia, subsequently found to have an LV thrombus secondary to TC. Diagnosis of TC was made challenging by the absence of chest pain. She required urgent arterial embolectomy and was treated with 6-month oral anticoagulation therapy. She was also commenced on beta-blocker and angiotensin-converting enzyme inhibitor treatment for the management of LV dysfunction. PMID- 27679726 TI - Imaging of juvenile idiopathic arthritis. Part I: Clinical classifications and radiographs. AB - Juvenile idiopathic arthritis is the most common autoimmune systemic disease of the connective tissue affecting individuals at the developmental age. Radiography is the primary modality employed in the diagnostic imaging in order to identify changes typical of this disease entity and rule out other bone-related pathologies, such as neoplasms, posttraumatic changes, developmental defects and other forms of arthritis. The standard procedure involves the performance of comparative joint radiographs in two planes. Radiographic changes in juvenile idiopathic arthritis are detected in later stages of the disease. Bone structures are assessed in the first place. Radiographs can also indirectly indicate the presence of soft tissue inflammation (i.e. in joint cavities, sheaths and bursae) based on swelling and increased density of the soft tissue as well as dislocation of fat folds. Signs of articular cartilage defects are also seen in radiographs indirectly - based on joint space width changes. The first part of the publication presents the classification of juvenile idiopathic arthritis and discusses its radiographic images. The authors list the affected joints as well as explain the spectrum and specificity of radiographic signs resulting from inflammatory changes overlapping with those caused by the maturation of the skeletal system. Moreover, certain dilemmas associated with the monitoring of the disease are reviewed. The second part of the publication will explain issues associated with ultrasonography and magnetic resonance imaging, which are more and more commonly applied in juvenile idiopathic arthritis for early detection of pathological features as well as the disease complications. PMID- 27679727 TI - Imaging of juvenile idiopathic arthritis. Part II: Ultrasonography and MRI. AB - Juvenile idiopathic arthritis is the most common autoimmune systemic disease of the connective tissue affecting individuals in the developmental age. Radiography, which was described in the first part of this publication, is the standard modality in the assessment of this condition. Ultrasound and magnetic resonance imaging enable early detection of the disease which affects soft tissues, as well as bones. Ultrasound assessment involves: joint cavities, tendon sheaths and bursae for the presence of synovitis, intraand extraarticular fat tissue to visualize signs of inflammation, hyaline cartilage, cartilaginous epiphysis and subchondral bone to detect cysts and erosions, and ligaments, tendons and their entheses for signs of enthesopathies and tendinopathies. Magnetic resonance imaging is indicated in children with juvenile idiopathic arthritis for assessment of inflammation in peripheral joints, tendon sheaths and bursae, bone marrow involvement and identification of inflammatory lesions in whole-body MRI, particularly when the clinical picture is unclear. Also, MRI of the spine and spinal cord is used in order to diagnose synovial joint inflammation, bone marrow edema and spondylodiscitis as well as to assess their activity, location, and complications (spinal canal stenosis, subluxation, e.g. in the atlantoaxial region). This article discusses typical pathological changes seen on ultrasound and magnetic resonance imaging. The role of these two methods for disease monitoring, its identification in the pre-clinical stage and establishing its remission are also highlighted. PMID- 27679728 TI - Inter-rater reliability in the classification of supraspinatus tendon tears using 3D ultrasound - a question of experience? AB - BACKGROUND: Three-dimensional (3D) ultrasound of the shoulder is characterized by a comparable accuracy to two-dimensional (2D) ultrasound. No studies investigating 2D versus 3D inter-rater reliability in the detection of supraspinatus tendon tears taking into account the level of experience of the raters have been carried out so far. OBJECTIVES: The aim of this study was to determine the inter-rater reliability in the analysis of 3D ultrasound image sets of the supraspinatus tendon between sonographer with different levels of experience. PATIENTS AND METHODS: Non-interventional, prospective, observational pilot study of 2309 images of 127 adult patients suffering from unilateral shoulder pain. 3D ultrasound image sets were scored by three raters independently. The intra-and interrater reliabilities were calculated. RESULTS: There was an excellent intra-rater reliability of rater A in the overall classification of supraspinatus tendon tears (2D vs 3D kappa = 0.892, pairwise reliability 93.81%, 3D scoring round 1 vs 3D scoring round 2 kappa = 0.875, pairwise reliability 92.857%). The inter-rater reliability was only moderate compared to rater B on 3D (kappa = 0.497, pairwise reliability 70.95%) and fair compared to rater C (kappa = 0.238, pairwise reliability 42.38%). CONCLUSIONS: The reliability of 3D ultrasound of the supraspinatus tendon depends on the level of experience of the sonographer. Experience in 2D ultrasound does not seem to be sufficient for the analysis of 3D ultrasound imaging sets. Therefore, for a 3D ultrasound analysis new diagnostic criteria have to be established and taught even to experienced 2D sonographers to improve reproducibility. PMID- 27679729 TI - Evaluation of the utility value of percutaneous drainage of symptomatic hepatic cysts combined with an obliteration attempt. AB - AIM: The goal of the paper was to evaluate the procedure of percutaneous drainage of symptomatic hepatic cysts under the transabdominal ultrasound control combined with obliteration. MATERIAL AND METHOD: Within the period from 2005 to 2015, 70 patients diagnosed with a simple hepatic cyst of symptomatic nature were subject to hospitalization and treated at the 2(nd) General, Gastroenterological and Cancer Surgery of the Alimentary System Center and Clinics of the Medical University of Lublin. All the patients subject to evaluation were qualified to percutaneous drainage under an ultrasound control. The drainage utilized typical sets of drains with the diameter of at least 9 F, most often of pigtail type. The fluid aspirated form the cyst was dispatched for complex laboratory testing. Further, a 10% sodium chloride solution was administered to the cyst through the drain, in the volume depending on the previous size of the cyst and the patient's reaction. RESULTS: Patients reported for a re-visit within the period from 3 to 9 months following the procedure. Complete obliteration of the cyst was confirmed only in 8 patients (11%). Cyst recurrence was reported in cases when during the ultrasound evaluation, the diameter of the cyst following aspiration and obliteration enlarged to over 75% of the initial dimension. In this group, in 10 out of 12 examined (83%) there was a relapse of the previously observed ailments. Among patients, who has a cyst imaged within the period of observation, which had the diameter from 50% to 75% of the previous size, only in 6 cases (37.5%) the initial symptoms relapsed. CONCLUSIONS: The utilization of a drainage and obliteration enables one to achieve the acceptable result of the therapy as well as significant decrease in the number of previously reported ailments and symptoms described. PMID- 27679730 TI - Is a fatty pancreas a banal lesion? AB - So far, a fatty pancreas has been related to obesity and the ageing processes in the body. The current list of pathogenetic factors of the condition is clearly extended with genetically conditioned diseases (cystic fibrosis, Shwachman Diamond syndrome and Johanson-Blizzard syndrome), pancreatitis, especially hereditary and obstructive, metabolic and hormonal disorders (hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hypercortisolemia), alcohol overuse, taking some medicines (especially adrenal cortex hormones), disease of the liver and visceral adiposis. As regards lipomatosis of that organ resulting mainly from dyslipidemia and hyperglycemia, the term "nonalcoholic fatty pancreas disease" was introduced. Experimental studies on animals and histological preparations of the pancreatic fragments show that the lipotoxicity of the collected adipocytes collected ion the organ release a cascade of proinflammatory phenomena, and even induces the processes of carcinogenesis. Pancreas adiposis is best defined in Computed Tomography and Magnetic Resonance Imaging. However, a series of works proved the usefulness in the diagnostics of that pathology of transabdominal and endoscopic ultrasonography. In that method, the degree of adiposis was based on the comparison of echogenicity of the pancreas and the liver, renal parenchyma, spleen and/or retroperitoneal adipose. Recently, the evaluation was expanded by the evaluation of the degree of pancreatic adipose with the pancreas-to-liver index, utilizing to that end a special computer program. According to our experience, the simplest solution is the method utilized by us. On one crosssection of the body of the pancreas, its echogenicity is assessed in comparison to retroperitoneal adipose and the visibility of the splenic vein, pancreatic duct and the major retroperitoneal vessels. Depending on the visualization of these structures, it is possible to determine the degree of pancreas adiposis. Such a study applies to 250 people, in whom the adiposis was detected in 16.5%, which is close to other cohort US examinations results. PMID- 27679732 TI - A review of ultrasonographic methods for the assessment of the anterior cruciate ligament in patients with knee instability - diagnostics using a posterior approach. AB - AIM: The purpose of the study was to improve the ultrasonographic assessment of the anterior cruciate ligament by an inclusion of a dynamic element. The proposed functional modification aims to restore normal posterior cruciate ligament tension, which is associated with a visible change in the ligament shape. This method reduces the risk of an error resulting from subjectively assessing the shape of the posterior cruciate ligament. It should be also emphasized that the method combined with other ultrasound anterior cruciate ligament assessment techniques helps increase diagnostic accuracy. METHODS: Ultrasonography is used as an adjunctive technique in the diagnosis of anterior cruciate ligament injury. The paper presents a sonographic technique for the assessment of suspected anterior cruciate ligament insufficiency supplemented by the use of a dynamic examination. This technique can be recommended as an additional procedure in routine ultrasound diagnostics of anterior cruciate ligament injuries. RESULTS: Supplementing routine ultrasonography with the dynamic assessment of posterior cruciate ligament shape changes in patients with suspected anterior cruciate ligament injury reduces the risk of subjective errors and increases diagnostic accuracy. This is important especially in cases of minor anterior knee instability and bilateral anterior knee instability. CONCLUSIONS: An assessment of changes in posterior cruciate ligament using a dynamic ultrasound examination effectively complements routine sonographic diagnostic techniques for anterior cruciate ligament insufficiency. PMID- 27679733 TI - Internal snapping hip syndrome in dynamic ultrasonography. AB - Snapping hip syndrome is an audible or palpable snap in a hip joint during movement which may be accompanied by pain or locking. It is typically seen in young athletes performing activities requiring repeated extreme movements of the hip. It may also follow a physical trauma, intramuscular injections or surgeries. There are two main forms of snapping hip: extra- or intra-articular. Extra articular snapping hip is elicited by an abnormal movement of specific tendons and is divided into two forms: internal and external. The internal form of snapping hip syndrome is attributed to an abrupt movement of an iliopsoas tendon against an iliopectineal eminence. Radiograph results in patients with this form of snapping tend to be normal. Dynamic ultrasound is the gold standard diagnostic technique in both forms of extra-articular snapping hip syndrome. The objective of the following text is to describe a step-by-step dynamic ultrasonography examination in internal extra-articular snapping hip syndrome in accordance to the proposed checklist protocol. To evaluate abrupt movement of an involved tendon, the patient needs to perform specific provocation tests during the examination. With its real-time imaging capabilities, dynamic ultrasonography detects the exact mechanism of the abnormal tendon friction during hip movement in a noninvasive way. It also allows for a diagnosis of additional hip tissue changes which may be causing the pain. PMID- 27679731 TI - Shear wave elastography with a new reliability indicator. AB - Non-invasive methods for liver stiffness assessment have been introduced over recent years. Of these, two main methods for estimating liver fibrosis using ultrasound elastography have become established in clinical practice: shear wave elastography and quasi-static or strain elastography. Shear waves are waves with a motion perpendicular (lateral) to the direction of the generating force. Shear waves travel relatively slowly (between 1 and 10 m/s). The stiffness of the liver tissue can be assessed based on shear wave velocity (the stiffness increases with the speed). The European Federation of Societies for Ultrasound in Medicine and Biology has published Guidelines and Recommendations that describe these technologies and provide recommendations for their clinical use. Most of the data available to date has been published using the Fibroscan (Echosens, France), point shear wave speed measurement using an acoustic radiation force impulse (Siemens, Germany) and 2D shear wave elastography using the Aixplorer (SuperSonic Imagine, France). More recently, also other manufacturers have introduced shear wave elastography technology into the market. A comparison of data obtained using different techniques for shear wave propagation and velocity measurement is of key interest for future studies, recommendations and guidelines. Here, we present a recently introduced shear wave elastography technology from Hitachi and discuss its reproducibility and comparability to the already established technologies. PMID- 27679734 TI - Physiological basis in the assessment of myocardial mechanics using speckle tracking echocardiography 2D. Part II. AB - In this paper, the authors attempt to concisely present the anatomical and pathophysiological bases as well as the principles for echocardiographic evaluation of mechanical aspects of cardiac function based on speckle tracking method. This technique uses a phenomenon involving the formation of characteristic image units, referred to as speckles or acoustic markers, which are stable during cardiac cycle, on a two-dimensional echocardiographic picture. Changes in the position of these speckles throughout the cardiac cycle, which are monitored and analyzed semi-automatically by a computer system, reflect deformation of both, cardiac ventricle as a whole as well as its individual anatomical segments. The values of strain and the strain rate, as well as the range and velocity of the movement of these markers, which are in close relationship with multiple hemodynamic parameters, can be visualized as various types of charts - linear, two- and three-dimensional - as well as numerical values, enabling deeper insight into the mechanical and hemodynamic aspects of cardiac function in health and disease. The use of information obtained based on speckle tracking echocardiography allows to understand previously unclear mechanisms of physiological and pathophysiological processes. The first part of the study discusses the formation of a two-dimensional ultrasound image and the speckles, as well as the technical aspects of tracking their movement. The second part presents in more detail the methodology of speckle-tracking echocardiography, the characteristic abnormalities of cardiac mechanics presenting in different clinical entities, and the limitations related to given clinical and technical issues. PMID- 27679735 TI - Fortuitous diagnosis of "full stomach" made by using ultrasonographic examination of the antrum in two elective patients. AB - We report two cases of patients presenting for elective surgery, in whom significant gastric contents were identified by performing fortuitous ultrasound examination of their antral area. The first patient presented for a day-case surgery scheduled under regional anesthesia. With his consent, ultrasound examination of the antral area was by chance performed within the context of training for this technique, showing significant solid contents in the stomach. The patient admitted that he had not respected preoperative fasting. The second patient was scheduled for an elective ophthalmologic surgery. Ultrasound examination of the antrum showed that the antrum was dilated, with significant solid and liquid gastric contents. This case may be related to a strongly delayed gastric emptying. These two cases demonstrate that some elective patients may present with significant gastric contents exposing them to the risk of pulmonary aspiration in the case of general anesthesia. PMID- 27679737 TI - Early High-Dose Caffeine Increases Seizure Burden in Extremely Preterm Neonates: A Preliminary Study. AB - Background: Although evidence suggests that methylxanthines may lower the seizure threshold, the effect of high-dose caffeine on seizure burden in preterm infants is not known. This study reports a secondary post hoc analysis of a randomized controlled trial of early high-dose caffeine citrate therapy in preterm infants, evaluating the effect of caffeine on the seizure burden using amplitude integrated electroencephalography (aEEG). Methods: Seventy-four preterm infants (<=30 weeks gestation) were randomized to receive high-dose (n = 37, 80 mg/kg over 36 hours) or standard-dose (n = 37, 30 mg/kg over 36 hours) caffeine citrate over the first 36 hours followed by standard maintenance therapy. Simultaneous recording of two-channel amplitude-integrated EEG was conducted over the first 72 hours of life. The primary outcome of this post hoc analysis was cumulative seizure burden over the first 72 hours of life, measured in seconds. Results: Fifteen infants were excluded due to short recordings (<=5 hours) or corrupted data files (n = 7 standard dose; n = 8 high dose). The high-dose caffeine group displayed a trend toward an increased incidence of seizures (40% vs. 58%; p = 0.1) and a threefold increase in seizure duration (48.9 vs. 170.9 seconds; p = 0.1). Conclusion: Early high-dose caffeine therapy was associated with a trend toward an increase in seizure incidence and burden. Future studies of alternative caffeine dosing regimens should include continuous EEG monitoring. PMID- 27679738 TI - The 2016 World Humanitarian Summit Report Card: Both Failing Marks and Substantive Gains for an Increasingly Globalized Humanitarian Landscape. AB - Outcomes of the World Humanitarian Summit were mixed with some refreshing new directions being endorsed and a lack of systemic reform. The selective agenda and OCHAs lack of success in engaging pre-meeting political participation not only hampered the Summit's ability to deal with global issues and institutional reform, but also alienated it from leading aid agencies and governments. The UN's failure to commit to humanitarian principles and global disarray of the humanitarian system indicates the need for extensive reform or a new global humanitarian body. This agency needs to employ a decentralized model to manage aid funds, assume coordination of international responses, resolve civil-military coordination, cater for people affected by both conflict and disasters, and professionalize the humanitarian career. PMID- 27679736 TI - Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome. AB - Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F] FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges. PMID- 27679739 TI - Isolation of Zika Virus Imported from Tonga into Australia. AB - INTRODUCTION: The globally emergent Zika virus (ZIKV) is a threat to Australia, given the number of imported cases from epidemic regions and the presence of competent mosquito vectors. We report the isolation of ZIKV from a female traveler who recently returned from Tonga to Brisbane, Queensland, Australia in 2016. METHODS: A specific TaqMan real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) assay was used to detect ZIKV in serum and urine samples. Conventional cell culture techniques and suckling mice were employed in an attempt to isolate ZIKV from serum and urine. RESULTS: A ZIKV isolate (TS17-2016) was recovered from the serum sample after one passage in suckling mouse brains and harvested 11 days post inoculation. Phylogenetic analysis of complete envelope (E) gene sequences demonstrated TS17-2016 shared 99.9% nucleotide identity with other contemporary sequences from Tonga 2016, Brazil 2015 and French Polynesia 2013 within the Asian lineage. DISCUSSION: This is the first known report of successful isolation of ZIKV from a human clinical sample in Australia and the first from a traveler from Tonga. This study highlights the potential difficulties in isolating ZIKV from acute clinical samples using conventional cell culture techniques, particularly in non-endemic countries like Australia where access to samples of sufficient viral load is limited. The successful isolation of TS17-2016 will be essential for continued investigations of ZIKV transmission and pathogenicity and will enable the advancement of new preventative control measures extremely relevant to the Australian and Pacific region. PMID- 27679740 TI - Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation. AB - BACKGROUND: The mdx mouse model for the fatal muscle wasting disease Duchenne Muscular Dystrophy (DMD) shows a very mild pathology once growth has ceased, with low levels of myofibre necrosis in adults. However, from about 3 weeks of post natal age, muscles of juvenile mdx mice undergo an acute bout of severe necrosis and inflammation: this subsequently decreases and stabilises to lower adult levels by about 6 weeks of age. Prior to the onset of this severe dystropathology, we have shown that mdx mice are deficient in the amino acid taurine (potentially due to weaning), and we propose that this exacerbates myofibre necrosis and inflammation in juvenile mdx mice. OBJECTIVES: The purpose of this study was to increase taurine availability to pre-weaned juvenile mdx mice (from 14 days of age), to evaluate the impact on levels of myofibre necrosis and inflammation (at 22 days) during the acute period of severe dystropathology. RESULTS: Untreated 22 day old mdx muscle was not deficient in taurine, with similar levels to normal C57 control muscle. However taurine treatment, which increased the taurine content of young dystrophic muscle (by 40%), greatly reduced myofibre necrosis (by 75%) and prevented significant increases in 3 markers of inflammation. CONCLUSION: Taurine was very effective at preventing the acute phase of muscle damage that normally results in myofibre necrosis and inflammation in juvenile mdx mice, supporting continued research into the use of taurine as a therapeutic intervention for protecting growing muscles of young DMD boys. PMID- 27679741 TI - DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex. AB - AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of "super elongation complexes" (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex. DDX6 is an evolutionarily conserved member of the DEAD-box RNA helicase family that is known to control miRNA and mRNA biology (translation, storage and degradation). Overexpressed DDX6 is associated with different cancer types and with c-Myc protein overexpression. We could demonstrate that DDX6 binds to 7SK snRNA and causes the release and transfer of P TEFb to the AF4/AF4N SEC. DDX6 also binds stably to AF4 and AF4N as demonstrated by GST pull-down and co-immunoprecipitation experiments. As a consequence, overexpression of either AF4/AF4N or DDX6 resulted in a strong increase of mRNA production (5-6 fold), while their simultaneous expression increased the cellular mRNA production by 11-fold. Conversely, the corresponding knockdown of DDX6 decreased mRNA production by 70%. In conclusion, AF4/AF4N and DDX6 represent key molecules for the elongation process of gene transcription and a model will be proposed for the hand-over process of P-TEFb to SECs. PMID- 27679742 TI - Small mammalian animal models of heart disease. AB - There is an urgent clinical need to develop new therapeutic approaches for treating cardiovascular disease, but the biology of cardiovascular regeneration is complex. Model systems are required to advance our understanding of the pathogenesis, progression, and mechanisms underlying cardiovascular disease as well as to test therapeutic approaches to regenerate tissue and restore cardiac function following injury. An ideal model system should be inexpensive, easily manipulated, reproducible, physiologically representative of human disease, and ethically sound. The choice of animal model needs to be considered carefully since it affects experimental outcomes and whether findings of the study can be reasonably translated to humans. This review presents a guideline for the commonly used small animal models (mice, rats, rabbits, and cats) used in cardiac research as an effort to standardize the most relevant procedures and obtain translatable and reproducible results. PMID- 27679743 TI - Myocardial energetics and the role of micronutrients in heart failure: a critical review. AB - Heart failure is a multifactorial disease with poor prognosis. There are many hypotheses regarding the cause of heart failure. Leading among them are the hemodynamic and the neuro-hormonal hypotheses. Although the energy depletion hypothesis has been fairly recent, there is evidence suggesting that declining bioenergy plays a major role in heart failure. This review explored the myocardial energy depletion hypothesis from the role of micronutrients in correcting and alleviating symptoms of heart failure. Even though focus was on key nutrients such as coenzyme Q10, thiamine, riboflavin, L-carnitine, and taurine, emphasis was on the combined effect of multiple micronutrients as a whole. Search from databases from 2000 to 2015 produced four clinical studies using multiple micronutrients on heart failure. Evidence from the studies show that using high doses of multiple micronutrients may have positive effects on heart failure and simultaneously support the myocardial energy depletion hypothesis. PMID- 27679744 TI - Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart. AB - Reactive oxygen species (ROS) generation has been implicated in many pathologies including ischemia/reperfusion (I/R) injury. This led to multiple studies on antioxidant therapies to treat cardiovascular diseases but paradoxically, results have so far been mixed as ROS production can be beneficial as a signaling mechanism and in cardiac protection via preconditioning interventions. We investigated whether the differential impact of increased ROS in injury as well as in protection could be explained by their site of production on the mitochondrial electron transport chain. Using amplex red to measure ROS production, we found that mitochondria isolated from hearts after I/R produced more ROS than non-ischemic when complex I substrate (glutamate/malate) was used. Interestingly, the substrates of complex II (succinate) and ubiquinone (sn glycerol 3-phosphate, G3P) produced less ROS in mitochondria from I/R hearts compared to normal healthy hearts. The inhibitors of complex I (rotenone) and complex III (antimycin A) increased ROS production when glutamate/malate and G3P were used; in contrast, they reduced ROS production when the complex II substrate was used. Mitochondrial calcium retention capacity required to induce mitochondrial permeability transition pore (mPTP) opening was measured using calcium green fluorescence and was found to be higher when mitochondria were treated with G3P and succinate compared to glutamate/malate. Furthermore, Langendorff hearts treated with glutamate/malate exhibited reduced cardiac functional recovery and increased myocardial infarct size compared to hearts treated with G3P. Thus, ROS production by the stimulated respiratory chain complexes I and III has opposite roles: cardio-deleterious when produced in complex I and cardio-protective when produced in complex III. The mechanism of these ROS involves the inhibition of the mPTP opening, a key event in cell death following ischemia/reperfusion injury. PMID- 27679745 TI - Documentation of various approaches and outcomes in patients on warfarin undergoing dental procedures: a review article. AB - Appropriate management of patients with mechanical prosthetic valves on warfarin during dental procedures is crucial. If the patients continue warfarin, they might develop bleeding, while interruption of therapy can cause thromboembolic events. Bridging therapy (mostly heparin) is used in some patients, while others stop medications. There is no unifying protocol. Information on management of patients on warfarin undergoing dental procedures in Saudi Arabia is lacking. Therefore, the current study aimed to provide more insight into various approaches utilized by clinicians to deal with such patients at a large teaching hospital in Riyadh, and to evaluate the frequency and severity of bleeding and thromboembolic complications during different types of dental procedures in this population. This was a cohort study. Patient records were used to collect data on peri-procedural management of patients on warfarin, continuation or interruption of warfarin therapy, as well as bleeding and thromboembolic complications. Fifty medical records were reviewed from March to October 2012. Regarding management, 10% had no proper documentation, 74% underwent bridging therapy, 12% discontinued warfarin therapy, and 4% continued warfarin. Of the patients, 31% had minor bleeding (15% in patients on bridging therapy and 16% in patients continuing warfarin). Thromboembolic complications were documented in 4%, (2% in those on bridging therapy and 2% in those discontinuing warfarin). Patients on bridging therapy (heparin) were admitted to the hospital for a mean of five days, and none of the other patients were admitted. Adopting the protocol to continue warfarin caused bleeding tendency that was controlled with the usual measures, with more cost effectiveness, and no thromboembolic risks. PMID- 27679746 TI - Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-gamma. AB - Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT2Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 ug/kg/hr) on blood pressure was tested in 9 week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively). Cardiac output was measured by echocardiography. Immunohistochemistry was performed to localize and quantify AT2Rs and p-Ser(1177) endothelial nitric oxide synthase (eNOS) levels in the aortic arch. PD123319 and GW-9662 were used to selectively block the AT2R and peroxisome proliferator activated receptor-gamma (PPAR-gamma), respectively. Ang II infusion decreased blood pressure by 12 mmHg (P < 0.001) in LCD/apoE((-/-)) mice without altering cardiac output; a response blocked by PD123319. Although, AT2R stimulation neither activated eNOS (p-Ser(1177)-eNOS) nor changed plasma NO metabolites, it caused an ~6-fold increase in VSMC PPAR-gamma levels (P < 0.001) and the AT2R mediated hypotension was abolished by GW-9662. AT2R-mediated hypotension was also inhibited by HCD, which selectively decreased VSMC AT2R expression by ~6-fold (P < 0.01). These findings suggest a novel pathway for the Ang II/AT2R-mediated hypotensive response that involves PPAR-gamma, and is down regulated by a HCD. PMID- 27679747 TI - Diabetic indicators are the strongest predictors for cardiovascular disease risk in African American adults. AB - African Americans have higher risk of developing type 2 diabetes and cardiovascular disease (CVD) compared to other racial groups. Modifiable and non modifiable factors play a role in the development of both diseases. This study assessed diabetes indicators in relation to other CVD risk factors taking into account confounders, among African American adults. This was a cross-sectional study in mid-life and older African Americans (>=45 years) who were recruited from the local churches. Fasting blood was collected and serum analyzed for diabetes indicators, apolipoproteins, adipokines, and lipid profile. CVD risk scores were determined using the American Heart Association and Framingham Risk Score assessments. Homeostasis Model Assessments (HOMAs) were calculated using glucose and insulin concentrations. Confounding variables were assessed by questionnaires. Data were analyzed using SPSS software, version 21, and p<0.05 was deemed significant. Descriptive statistics was used to analyze continuous variables. Frequencies and percentages were used to examine categorical variables. T-tests compared different groups while Pearson correlations provided preliminary relationships and determined variables for multiple regression analyses. A total of n=79 participants were evaluated (69% women), 59.3+/-9.2 years, BMI=34.7+/-8.3 (mean +/- SD). As expected, AA men had higher fasting blood glucose than women (123.6+/-54.9 mg/dL versus 99.0+/-21.8 mg/dL), and AA women had higher insulin (11.8+/-13.1 mg/dL versus 7.6+/-6.0 mg/dL). Our study confirmed that it is likely for AA men to have significantly lower adiponectin concentrations in comparison to AA women. Based on the CVD risk assessments, men had a significantly higher risk of developing CVD than women, which has been shown previously. Apolipoproteins, adipokines, and lipid profile also negatively influenced the cardiovascular health outcomes in men. Dietary intake, probably by influencing participants' weight/adiposity, contributed to the differences in cardiovascular outcomes between men and women. In conclusion, the findings of this study revealed that diabetes and serum glucose appeared to be the leading factors for high CVD risk, on the contrary to some other indicators reported in some studies, e.g. hypertension or dyslipidemia. PMID- 27679748 TI - Irreversible Hemichorea-Hemiballism in a Case of Nonketotic Hyperglycemia Presenting as the Initial Manifestation of Diabetes Mellitus. AB - BACKGROUND: Hemichorea-hemiballism (HCHB) is a hyperkinetic movement disorder with features of both chorea and ballism occurring on the same side. CASE REPORT: We present a case of HCHB due to nonketotic hyperglycemia (NKH) that was the initial presentation of diabetes and was irreversible clinically even after 6 months of optimal blood sugar control. DISCUSSION: Although HCHB due to hyperglycemia is a potentially reversible condition in the majority of patients, prolonged uncontrolled hyperglycemia may cause ischemic insult and persistent symptoms. Hyperglycemia should always be kept in the list of differentials while dealing with patients who are newly diagnosed with HCHB. PMID- 27679749 TI - Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review. AB - Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies. Recent Advances: Encouraged by the results of NPWT in noncombat-related wounds, the military surgeons during Operation Iraqi Freedom and Operation Enduring Freedom used this novel method in a large percentage of combat wounds, with gratifying results. The mechanism of NPWT in wound healing is multifactorial and often complex reconstructive procedure can be avoided in a combat trauma setting. Critical Issues: Wounds sustained in military trauma are heavily contaminated with dirt, patient clothing, and frequently associated with extensive soft tissue loss and osseous destruction. Delay in evacuation during an ongoing conflict carries the risk of systemic infection. Early debridement is indicated followed by delayed closure of wounds. NPWT helps to provide temporary wound cover during the interim period of debridement and wound closure. Future Directions: Future area of research in combat wounds is related to abdominal trauma with loss of abdominal wall. The concept of negative pressure incisional management system in patients with a high risk of wound breakdown following surgery is under review, and may be of relevance in combat wounds. PMID- 27679750 TI - Personalized Medicine in Ocular Fibrosis: Myth or Future Biomarkers. AB - Significance: Fibrosis-related events play a part in the pathogenesis or failure of treatment of virtually all the blinding diseases around the world, and also account for over 40% of all deaths. It is well established that the eye and other tissues of some group of patients, for example Afro-Caribbean people, scar worse than others. However, there is a current lack of reliable biomarkers to stratify the risk of scarring and postsurgical fibrosis in the eye. Recent Advances: Recent studies using genomics, proteomics, metabolomics, clinical phenotyping, and high-resolution in vivo imaging techniques have revealed potential novel biomarkers to identify and stratify patients at risk of scarring in different fibrotic eye diseases. Critical Issues: Most of the studies, to date, have been done in animals or small cohorts of patients and future research is needed to validate these results in large longitudinal human studies. Detailed clinical phenotyping and effective biobanking of patient tissues will also be critical for future biomarker research in ocular fibrosis. Future Directions: The ability to predict the risk of scarring and to tailor the antifibrotic treatment regimen to each individual patient will be an extremely useful tool clinically to prevent undertreating, or exposing patients to unnecessary treatments with potential side effects. An exciting future prospect will be to use new advances in genotyping, namely next-generation whole genome sequencing like RNA-Seq, to develop a customized gene chip in ocular fibrosis. Successful translation of future biomarkers to benefit patient care will also ultimately require a strong collaboration between academics, pharmaceutical, and biotech companies. PMID- 27679751 TI - Plastic Surgery Challenges in War Wounded I: Flap-Based Extremity Reconstruction. AB - Scope and Significance: Reconstruction of traumatic injuries requiring tissue transfer begins with aggressive resuscitation and stabilization. Systematic advances in acute casualty care at the point of injury have improved survival and allowed for increasingly complex treatment before definitive reconstruction at tertiary medical facilities outside the combat zone. As a result, the complexity of the limb salvage algorithm has increased over 14 years of combat activities in Iraq and Afghanistan. Problem: Severe poly-extremity trauma in combat casualties has led to a large number of extremity salvage cases. Advanced reconstructive techniques coupled with regenerative medicine applications have played a critical role in the restoration, recovery, and rehabilitation of functional limb salvage. Translational Relevance: The past 14 years of war trauma have increased our understanding of tissue transfer for extremity reconstruction in the treatment of combat casualties. Injury patterns, flap choice, and reconstruction timing are critical variables to consider for optimal outcomes. Clinical Relevance: Subacute reconstruction with specifically chosen flap tissue and donor site location based on individual injuries result in successful tissue transfer, even in critically injured patients. These considerations can be combined with regenerative therapies to optimize massive wound coverage and limb salvage form and function in previously active patients. Summary: Traditional soft tissue reconstruction is integral in the treatment of war extremity trauma. Pedicle and free flaps are a critically important part of the reconstructive ladder for salvaging extreme extremity injuries that are seen as a result of the current practice of war. PMID- 27679752 TI - Plastic Surgery Challenges in War Wounded II: Regenerative Medicine. AB - Background: A large volume of service members have sustained complex injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). These injuries are complicated by contamination with particulate and foreign materials, have high rates of bacterial and/or fungal infections, are often composite-type defects with massive soft tissue wounds, and usually have multisystem involvement. While traditional treatment modalities remain a mainstay for optimal wound care, traditional reconstruction approaches alone may be inadequate to fully address the scope and magnitude of such massive complex wounds. As a result of these difficult clinical problems, the use of regenerative medicine therapies, such as autologous adipose tissue grafting, stem cell therapies, nerve allografts, and dermal regenerate templates/extracellular matrix scaffolds, is increased as adjuncts to traditional reconstructive measures. Basic and Clinical Science Advances: The beneficial applications of regenerative medicine therapies have been well characterized in both in vitro studies and in vivo animal studies. The use of these regenerative medicine techniques in the treatment of combat casualty injuries has been increasing throughout the recent war conflicts. Clinical Care Relevance: Military medicine has shown positive results when utilizing certain regenerative medicine modalities in treating complex war wounds. As a result, multi-institution clinical trials are underway to further evaluate these observations and reconstruction measures. Conclusion: Successful combat casualty wound care often requires a combination of traditional aspects of the reconstructive ladder/elevator with adoption of various regenerative medicine therapies. Due to the recent OIF/OEF conflicts, a high volume of combat casualties have benefited from adoption of regenerative medicine therapies and increased access to innovative clinical trials. Furthermore, many of these patients have had long-term follow-up to report on clinical outcomes that substantiate current treatment paradigms and concepts within regenerative medicine, reconstructive, and rehabilitation care. These results are applicable to not only combat casualty care but also to nonmilitary patients. PMID- 27679754 TI - A UK student survey investigating the effects of consuming alcohol mixed with energy drinks on overall alcohol consumption and alcohol-related negative consequences. AB - Previous research reported positive associations between alcohol mixed with energy drink (AMED) consumption and overall alcohol consumption. However, results were largely based on between-subjects comparisons comparing AMED consumers with alcohol-only (AO) consumers, and therefore cannot sufficiently control for differences in personal characteristics between these groups. In order to determine whether AMED consumers drink more alcohol on occasions they consume AMED compared to those when they drink AO additional within-subjects comparisons are required. Therefore, this UK student survey assessed both alcohol consumption and alcohol-related negative consequences when consumed alone and when mixed with energy drinks, using a within-subject design. A total of 1873 students completed the survey, including 732 who consumed AMED. It was found that AMED consumers drank significantly less alcohol when they consumed AMED compared to when they drank AO (p < 0.001). In line with reduced alcohol consumption significantly fewer negative alcohol-related consequences were reported on AMED occasions compared to AO occasions (p < 0.001). These findings suggest that mixing alcohol with energy drinks does not increase total alcohol consumption or alcohol-related negative consequences. PMID- 27679756 TI - Infantile Pasteurella multocida meningitis. PMID- 27679753 TI - Cytokine-Rich Adipose Tissue Extract Production from Water-Assisted Lipoaspirate: Methodology for Clinical Use. AB - Proper functioning wound healing strategies are sparse. Adequate vascular formation to the injured area, as well as replacement of the volume loss, is fundamental in soft tissue repair. Tissue engineering strategies have been proposed for the treatment of these injury sites. Novel cell-free substance, human adipose tissue extract (ATE), has been previously shown to induce in vitro angiogenesis and adipogenesis and in vivo soft tissue formation. This study reports the translation of ATE preparation from laboratory to the operating room (OR). ATE samples for this study were derived from adipose tissue obtained with the water-jet assisted liposuction technique from 27 healthy patients. The variables studied included incubation time (15, 30, and 45 min), temperature (room temperature vs. 37 degrees C), and filter type to determine the optimal method yielding the most consistent total protein content, as well as consistent and high expression of adipose-derived growth factors and cytokines, including: vascular endothelial growth factor, basic fibroblast growth factor, interleukin 6, adiponectin, leptin, and insulin-like growth factor. Following the optimization, samples were produced in the OR and tested for their sterility. No significant differences were observed when comparing extract incubation time points or incubation temperature. Nonetheless, when studying the different filter types used, a syringe filter with PES membrane with larger filter area showed significantly higher protein concentration (p <= 0.018). When studying the different growth factor concentrations, ELISA results showed less variation in cytokine concentrations in the OR samples with the optimized protocol. All of the OR samples were tested sterile. The devised protocol is an easy and reproducible OR-ready method for ATE generation. As an attractive source of growth factors, ATE is a promising alternative in the vast field of tissue engineering. Its clinical applications include volume replacement as a complement to fillers and improvement of the permanence of fat grafts and wound healing, among other bioactive functions. PMID- 27679755 TI - Chikungunya fever presenting with protracted severe pruritus. AB - Travelers returning from the tropics often present with rash/fever. Those with rash/fever and myalgias/arthralgias are most likely due to chikungunya fever, dengue fever, or Zika virus. In these arthropod viral transmitted infections, the rash may be pruritic. The case presented here is that of chikungunya fever remarkable for the intensity and duration of her pruritis. PMID- 27679757 TI - Community-acquired lobar pneumonia encountered at autopsy. PMID- 27679758 TI - Leiomyosarcoma of the Inferior Vena Cava With Kidney Invasion. AB - Primary leiomyosarcomas of the inferior vena cava (IVC) are rare tumors associated with poor prognosis, and surgical resection with the goal of obtaining negative margins is the gold standard for initial treatment. Tumor characteristics of both extraluminal extension into renal parenchyma and intraluminal extension of the subdiaphragmatic IVC are even less common. The prognosis of vascular leiomyosarcomas is determined by the location and the size of the tumor, as these factors determine the risk of local recurrence and metastasis. We present a case of a 30-year old female incidentally found to have a 14 cm right renal mass and IVC thrombus. PMID- 27679760 TI - Splenogonadal Fusion: A Rare Benign Testicular Mass in a 55-Year-Old Male. AB - Splenogonadal fusion (SGF) is a rare cause of testicular mass with the vast majority of cases presenting in men under the age of 30 and represents a diagnostic challenge. Discontinuous splenogonadal fusion presenting as a new testicular mass in a 55-year-old man is discussed to aid other surgeons in diagnosing this condition. PMID- 27679759 TI - Prostatic Adenocarcinoma With Hormone Exposure Related Changes in a Patient With Hepatic Cirrhosis - Value of Autopsy in a Case Report. AB - Hepatic cirrhosis is commonly associated with hyperestrogenism. Previous studies have reported morphologic changes in benign and malignant prostate tissue exposed to estrogen or anti-androgens. To our knowledge, histopathologic features of prostatic adenocarcinoma in patients with cirrhosis have not been well-reported. We present a case of incidental, but pathologically significant, prostatic adenocarcinoma detected on autopsy in a 67-year-old male patient with cirrhosis and spider angiomata. The morphologic and immunohistochemical features (including variable ERG expression) of the prostatic adenocarcinoma were consistent with hormone exposure related changes, suggesting that cirrhosis-induced elevated estrogen-to-testosterone ratio and exogenous hormone therapy might induce similar phenotypes. PMID- 27679761 TI - Tumor Seeding With Renal Cell Carcinoma After Renal Biopsy. AB - Tumor seeding following biopsy of renal cell carcinoma is extremely rare with an incidence of 1:10.000. In this paper two cases with multiple recurrent RRC metastasis in the biopsy tract following biopsy of renal tumor is presented and the current literature is shortly discussed. PMID- 27679762 TI - Prostatic Leiomyoma: A Case Report. AB - A pure leiomyoma of the prostate is a rare tumor. Less than 30 cases about prostatic leiomyoma have been reported. Pathologic anatomy examination is the only medium for definitive diagnosis and is important to rule out malignancies such as leiomyosarcoma. We describe an accidental finding of a tumor in the right prostate lobe of a 54 year old man, who was diagnosed with prostatic leiomyoma and treated with open radical prostatectomy. PMID- 27679763 TI - Science in the UK - whereto now? PMID- 27679765 TI - The mediating role of social capital in the association between neighbourhood income inequality and body mass index. AB - Background: Neighbourhood income inequality may contribute to differences in body weight. We explored whether neighbourhood social capital mediated the association of neighbourhood income inequality with individual body mass index (BMI). Methods: A total of 4126 adult participants from 48 neighbourhoods in France, Hungary, the Netherlands and the UK provided information on their levels of income, perceptions of neighbourhood social capital and BMI. Factor analysis of the 13-item social capital scale revealed two social capital constructs: social networks and social cohesion. Neighbourhood income inequality was defined as the ratio of the amount of income earned by the top 20% and the bottom 20% in a given neighbourhood. Two single mediation analyses-using multilevel linear regression analyses-with neighbourhood social networks and neighbourhood social cohesion as possible mediators-were conducted using MacKinnon's product-of-coefficients method, adjusted for age, gender, education and absolute household income. Results: Higher neighbourhood income inequality was associated with elevated levels of BMI and lower levels of neighbourhood social networks and neighbourhood social cohesion. High levels of neighbourhood social networks were associated with lower BMI. Results stratified by country demonstrate that social networks fully explained the association between income inequality and BMI in France and the Netherlands. Social cohesion was only a significant mediating variable for Dutch participants. Conclusion: The results suggest that in some European urban regions, neighbourhood social capital plays a large role in the association between neighbourhood income inequality and individual BMI. PMID- 27679767 TI - Neuroinflammation and cytokine abnormality in major depression: Cause or consequence in that illness? AB - Depression results from changes in the central nervous system (CNS) that may result from immunological abnormalities. The immune system affects the CNS through cytokines, which regulate brain activities and emotions. Cytokines affect two biological systems that are most associated with the pathophysiology of depression: The hypothalamic-pituitary-adrenal axis and the catecholamine/sympathetic nervous system. Neuroinflammation and cytokines affect the brain signal patterns involved in the psychopathology of depression and the mechanisms of antidepressants, and they are associated with neurogenesis and neural plasticity. These observations suggest that neuroinflammation and cytokines might cause and/or maintain depression, and that they might be useful in the diagnosis and prognosis of depression. This psychoneuroimmunologic perspective might compensate for some of the limitations of the monoamine theory by suggesting that depression is a result of a failure to adapt to stress and that inflammatory responses and cytokines are involved in this process. In this review, the interactions of cytokines with the CNS, neuroendocrine system, neurotransmitters, neurodegeneration/neurogenesis, and antidepressants are discussed. The roles of cytokines in the etiology and psychopathology of depression are examined. The use of cytokine inhibitors or anti-inflammatory drugs in depression treatment is explored. Finally, the significance and limitations of the cytokine hypothesis are discussed. PMID- 27679769 TI - Ecological Momentary Assessment with smartphones for measuring mental health problems in adolescents. AB - AIM: To analyze the viability of Ecological Momentary Assessment (EMA) for measuring the mental states associated with psychopathological problems in adolescents. METHODS: In a sample of 110 adolescents, a sociodemographic data survey and an EMA Smartphone application over a one-week period (five times each day), was developed to explore symptom profiles, everyday problems, coping strategies, and the contexts in which the events take place. RESULTS: The positive response was 68.6%. Over 2250 prompts about mental states were recorded. In 53% of situations the smartphone was answered at home, 25.5% of cases they were with their parents or with peers (20.3%). Associations were found with attention, affective and anxiety problems (P < 0.001) in the participants who took longer to respond to the EMA app. Anxious and depressive states were highly interrelated (rho = 0.51, P < 0.001), as well as oppositional defiant problems and conduct problems (rho = 0.56, P < 0.001). Only in 6.2% of the situations the subjects perceived they had problems, mainly associated with inter-relational aspects with family, peers, boyfriends or girlfriends (31.2%). We also found moderate-high reliability on scales of satisfaction level on the context, on positive emotionality, and on the discomfort index associated with mental health problems. CONCLUSION: EMA methodology using smartphones is a useful tool for understanding adolescents' daily dynamics. It achieved moderate-high reliability and accurately identified psychopathological manifestations experienced by community adolescents in their natural context. PMID- 27679768 TI - Gene environment interaction in periphery and brain converge to modulate behavioral outcomes: Insights from the SP1 transient early in life interference rat model. AB - It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages. The present article reviews the main theoretical and practical concepts in the research of gene environment interaction, emphasizing the need for models simulating real life complexity. We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes, by hindering the activity of the ubiquitous transcription factor specificity protein 1 (Sp1) is followed by later-in-life exposure of rats to stress. Finally, this review discusses the role of peripheral processes in behavioral responses, with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes. We suggest that models, which take into account the tripartite reciprocal interaction between the central nervous system, peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior. PMID- 27679770 TI - Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia. AB - AIM: To define regional grey-matter abnormalities in schizophrenia patients with poor insight (Insight(-)), relative to patients with preserved clinical insight (Insight(+)), and healthy controls. METHODS: Forty stable schizophrenia outpatients (20 Insight(-) and 20 Insight(+)) and 20 healthy controls underwent whole brain magnetic resonance imaging (MRI). Insight in all patients was assessed using the Birchwood Insight Scale (BIS; a self-report measure). The two patient groups were pre-selected to match on most clinical and demographic parameters but, by design, they had markedly distinct BIS scores. Voxel-based morphometry employed in SPM8 was used to examine group differences in grey matter volumes across the whole brain. RESULTS: The three participant groups were comparable in age [F(2,57) = 0.34, P = 0.71] and the patient groups did not differ in age at illness onset [t(38) = 0.87, P = 0.39]. Insight(-) and Insight(+) patient groups also did not differ in symptoms on the Positive and Negative Syndromes scale (PANSS): Positive symptoms [t(38) = 0.58, P = 0.57], negative symptoms [t(38) = 0.61, P = 0.55], general psychopathology [t(38) = 1.30, P = 0.20] and total PANSS scores [t(38) = 0.21, P = 0.84]. The two patient groups, as expected, varied significantly in the level of BIS-assessed insight [t(38) = 12.11, P < 0.001]. MRI results revealed lower fronto-temporal, parahippocampal, occipital and cerebellar grey matter volumes in Insight(-) patients, relative to Insight(+) patients and healthy controls (for all clusters, family-wise error corrected P < 0.05). Insight(+) patient and healthy controls did not differ significantly (P > 0.20) from each other. CONCLUSION: Our findings demonstrate a clear association between poor clinical insight and smaller fronto temporal, occipital and cerebellar grey matter volumes in stable long-term schizophrenia patients. PMID- 27679771 TI - Stressful life events and psychosocial correlates of pediatric inflammatory bowel disease activity. AB - AIM: To investigate the association of psychiatric and psychosocial correlates with inflammatory bowel disease (IBD) activity in children and adolescents. METHODS: A total of 85 pediatric IBD patients (in remission or active state of the disease) and their parents completed a series of questionnaires and semi structured interviews measuring life events, depression, anxiety, family dysfunction, and parent mental health. Differences between the remission and the IBD active group and the association of any significant variable with the disease activity state were examined. RESULTS: Parents of children being in active state of the disease reported more life events (P = 0.005) and stressful life events (P = 0.048) during the past year and more mental health symptoms (P < 0.001), while the children themselves reported higher levels of anxiety symptoms (P = 0.017) compared to the remission group. In the logistic regression multivariate analysis, the only predictor which had a significant positive effect on the probability of the patients being in active state was parent mental health symptoms (OR = 4.8; 95%CI: 1.2-25.8). CONCLUSION: Life events, child anxiety and parent mental health symptoms may be important correlates of pediatric IBD activity and targets of thorough assessment and treatment. PMID- 27679775 TI - Oral but not written test anxiety is related to social anxiety. AB - AIM: To examine the associations of test anxiety (TA) in written vs oral exam situations with social anxiety (SA). METHODS: A convenience sample of 204 students was recruited at the Technische Universitat Dresden (TU Dresden, Germany) and contacted via e-mail asking to complete a cross-sectional online survey based on established questionnaires. The study protocol was approved by the ethics committee of the TU Dresden. Full data of n = 96 students were available for dependent t-tests and correlation analyses on the associations of SA and TA respectively with trigger events, cognitions, safety behaviors, physical symptoms and depersonalization. Analyses were run using SPSS. RESULTS: Levels of TA were higher for fear in oral exams than for fear in written exams (M = 48.1, SD = 11.5 vs M = 43.7, SD = 10.1 P < 0.001). Oral TA and SA were positively correlated (Spearman's r = 0.343, P < 0.001; Pearson's r = 0.38, P < 0.001) contrasting written TA and SA (Spearman's r = 0.17, P > 0.05; Pearson's r = 0.223, P > 0.05). Compared to written TA, trigger events were more often reported for oral TA (18.2% vs 30.3%, P = 0.007); which was also accompanied more often by test-anxious cognitions (7.9% vs 8.5%, P = 0.001), safety behavior (8.9% vs 10.3%, P < 0.001) and physical symptoms (for all, P < 0.001). CONCLUSION: Written, but not oral TA emerged being unrelated to SA and may rather not be considered as a typical facet of SA disorder. PMID- 27679773 TI - Chronic pelvic pain, psychiatric disorders and early emotional traumas: Results of a cross sectional case-control study. AB - AIM: To compare the prevalence of psychiatric disorders and early emotional traumas between women with chronic pelvic pain (CPP) and healthy women. METHODS: One hundred women in reproductive age, 50 of them had CPP (according to the criteria set by the International Association for Study of Pain), and 50 were considered healthy after the gynecological evaluation. The eligibility criteria were defined as follows: chronic or persistent pain perceived in the pelvis related structures (digestive, urinary, genital, myofascial or neurological systems). Only women in reproductive age with acyclic pain for 6 mo, or more, were included in the present study. Menopause was the exclusion criterion. The participants were grouped according to age, school level and socio-economic status and were individually assessed through DSM-IV Structured Clinical Interview (SCID-I) and Early Trauma Inventory Self-report - short form (ETISR-SF Brazilian version). Descriptive statistics, group comparison tests and multivariate logistics regression were used in the data analysis. RESULTS: The early emotional traumas are highly prevalent, but their prevalence did not differ between the two groups. The current Major Depressive Disorder was more prevalent in women with CPP. The CPP was associated with endometriosis in 48% of the women. There was no difference in the prevalence of disorders when endometriosis was taken into account (endometriosis vs other diseases: P > 0.29). The current Major Depressive Disorder and the Bipolar Disorder had greater occurrence likelihood in the group of women with CPP (ODDS = 5.25 and 9.0). CONCLUSION: The data reinforce the link between mood disorders and CPP. The preview evidences about the association between CPP and early traumas tended not to be significant after a stronger methodological control was implemented. PMID- 27679774 TI - Self-reported and behavioural impulsivity in anorexia nervosa. AB - AIM: To examine how self-reported and behavioural impulsivity are related in anorexia nervosa (AN). METHODS: Twenty-four females with AN and 25 healthy controls (HC) participant in the study. Self-reported impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). The scale yields three second order factors: Attentional, motor and non-planning. Behavioural impulsivity was investigated with the continuous performance test (CPT), a computer-based task of sustained attention in which numbers are flashed briefly on screen and participants are required to click the mouse when the same number appears consecutively. The rate of commission and omission errors can be used a measure of behavioural imulsivity. RESULTS: AN participants self-reported increased attentional [AN: 20.67 (3.64), HC: 13.88 (2.91), P = 0.001] and reduced motor impulsivity [AN: 11.55 (2.28), HC: 14.08 (2.78), P = 0.002]. The rate of omission or commission errors on the CPT did not differ between groups (P > 0.05). BIS-11 and CPT measures did not significantly correlate, but attentional impulsivity was related to negative mood states in AN (depression: r = 0.52, P = 0.010, anxiety: r = 0.55, P = 0.006, stress: r = 0.57, P = 0.004). CONCLUSION: The discrepancy between self-reported and behavioural impulsivity are discussed in terms of perfectionism in AN. Furthermore, it is suggested that improving negative mood states may resolve this inconsistency in AN. PMID- 27679772 TI - Self-worth and psychological adjustment of obese children: An analysis through the Draw-A-Person. AB - AIM: To investigate psychopathological correlates of child obesity via the Draw-A Person test (DAP). METHODS: The participants were 50 children with a mean age of 9.74 years. Body mass index (BMI) was used as a measure of body fat. Children were divided into normal (n = 17), overweight (n = 14) and obese (n = 19). Two qualitative methods of scoring the DAP based on an integrative approach were used to assess self-concept (ESW) and overall level of children's adjustment (EAC). A procedure for judging interpretative skills of clinicians was implemented before they evaluated children's drawings. RESULTS: As predicted by our hypothesis, BMI was negatively correlated with ESW, r (50) = -0.29, P < 0.05, but not with EAC, r (50) = - 0.08, P = ns. To evaluate the effect of gender, Pearson correlations were re-computed regrouping the sample accordingly: BMI and EAC reached a significant negative correlation in female subjects, r (24) = -0.36, P < 0.05, and a positive correlation in male subjects, r (26) = 0.37, P = < 0.05; negative correlation between BMI and ESW became stronger in females, r (24) = -0.51, P < 0.01 but not in males, whose correlation disappeared resulting not-significant, r (26) = -0.06, P = ns. No effect of age was found. Results indicate that obesity has a negative correlation exclusively on overall adjustment and self-concept in female children. CONCLUSION: It was concluded that there is a negative bias toward females that reveals how the stigma of obesity is widespread in Western society. PMID- 27679776 TI - Agreement and conversion formula between mini-mental state examination and montreal cognitive assessment in an outpatient sample. AB - AIM: To explore the agreement between the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) within community dwelling older patients attending an old age psychiatry service and to derive and test a conversion formula between the two scales. METHODS: Prospective study of consecutive patients attending outpatient services. Both tests were administered by the same researcher on the same day in random order. RESULTS: The total sample (n = 135) was randomly divided into two groups. One to derive a conversion rule (n = 70), and a second (n = 65) in which this rule was tested. The agreement (Pearson's r) of MMSE and MoCA was 0.86 (P < 0.001), and Lin's concordance correlation coefficient (CCC) was 0.57 (95%CI: 0.45-0.66). In the second sample MoCA scores were converted to MMSE scores according to a conversion rule from the first sample which achieved agreement with the original MMSE scores of 0.89 (Pearson's r, P < 0.001) and CCC of 0.88 (95%CI: 0.82-0.92). CONCLUSION: Although the two scales overlap considerably, the agreement is modest. The conversion rule derived herein demonstrated promising accuracy and warrants further testing in other populations. PMID- 27679777 TI - Comparative effectiveness of quetiapine and haloperidol in delirium: A single blind randomized controlled study. AB - AIM: To evaluate the effectiveness of quetiapine and haloperidol in patients of delirium referred to psychiatry consultation liaison services. METHODS: The study followed a single blind randomised controlled trial design. Thirty-two patients in the haloperidol group and 31 patients in the quetiapine group were assessed at the baseline and 6 consecutive days. Flexible dosing regimen (haloperidol: 0.25 1.25 mg; quetiapine 12.5-75 mg/d) was used. Delirium Rating Scale-Revised-98 (DRS R-98) and mini mental status examination (MMSE) were the primary and secondary efficacy measures respectively. RESULTS: Baseline DRS-R-98 severity score and MMSE scores did not differ between the 2 study groups. From baseline to day 6, there was significant reduction in the total DRS-R-98 scores, DRS-R-98 cognitive domain scores, DRS-R-98 non-cognitive domain scores and significant increase in the MMSE scores in both the groups. Both the groups did not differ on any of the assessments in terms of DRS-R98 and MMSE scores. The effectiveness of both the medications was similar in adult and elderly (>= 60 years) patients. At the end of the trial, 68.75% and 67.74% of subjects in the haloperidol and quetiapine group respectively had mean DRS-R-98 scores below 10. By 6(th) day, 12 (37.5%) patients in haloperidol group and 9 (29.03%) patients in the quetiapine group had DRS-R98 score of "0" with no significant difference between the two groups (P = 0.47). CONCLUSION: Quetiapine is as effective as haloperidol in the management of delirium. PMID- 27679778 TI - Cognitive behavioural therapy for auditory hallucinations in schizophrenia: A review. AB - AIM: To provide an updated of recent findings about efficacy of cognitive behavior therapy (CBT) in reduction of command hallucinations. METHODS: PubMed/MEDLINE, Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, ClinicalTrial.gov searches were performed using the keywords "hallucinations", "behavioural therapy" and " cognitive therapy" in order to identify relevant articles published during the years of 2011 to 2016. No language limits were used. Studies conducted within control group, reviews, editorials, were excluded. Data on efficacy, acceptability and tolerability were extracted by three authors independently. Disagreements were resolved in a consensus meeting or by another reviewer. RESULTS: A total of eight articles were eligible for inclusion. Two are randomized clinical trials (RCTs) and six are observational studies. The two RCTs included showed a greater efficacy of CBT compared to standard care on auditory hallucinations (AHs). Nevertheless, they considered different CBT models, particularly Treatment of Resistant Command Hallucinations and Cognitive Therapy for Command Hallucinations. As regards non RCT-studies, all papers included showed reduction on frequency and severity of AHs and distress related to them. However, the lack of content details within non RCTs studies decreased their comparability. In terms of predictive variables, our findings show that negative symptoms at baseline appeared to be the strongest predictor of the treatment efficacy. Indeed, negative symptoms showed a significant negative correlation on outcome. CONCLUSION: Although more conclusive studies are still needed, we found some preliminary evidence for the efficacy of CBT in the treatment of command hallucinations. PMID- 27679779 TI - Understanding the paranoid psychosis of James: Use of the repertory grid technique for case conceptualization. AB - In this paper we illustrate the potential of the repertory grid technique as an instrument for case formulation and understanding of the personal perception and meanings of people with a diagnosis of psychotic disorders. For this purpose, the case of James is presented: A young man diagnosed with schizophrenia and personality disorder, with severe persecutory delusions and other positive symptoms that have not responded to antipsychotic medication, as well with depressive symptomatology. His case was selected because of the way his symptoms are reflected in his personal perception of self and others, including his main persecutory figure, in the different measures that result from the analysis of his repertory grid. Some key clinical hypotheses and possible targets for therapy are discussed. PMID- 27679780 TI - CD4-positive diffuse large B-cell lymphoma: A variant with aggressive clinical potential. AB - CD4 expression is rare in diffuse large B-cell lymphoma (DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4(+) DLBCL and one CD4(+) primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20 (5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved (67%). Patients received chemotherapy +/- radiation (6/6) and bone marrow transplant (2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4(+) DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively. PMID- 27679781 TI - Modified skin bridge technique for ilio-inguinal lymph node dissection: A forgotten technique revisited. AB - Ilio-inguinal lymph node dissection (IILD) is a commonly performed surgical procedure for a number of malignant conditions involving mainly the male and female genitalia, and the skin; however the postoperative morbidity of IILD, due to high frequency of flap necrosis, wound infection and seroma formation, has always been a major concern for the surgeons. The aim of the study is to highlight a modified skin bridge technique of IILD using two parallel curvilinear incisions to minimize postoperative skin flap necrosis. This technique was successfully employed in 38 IILD during May 2012 to November 2013. None of the patient had flap necrosis. Two patients developed seroma while another two patients had superficial surgical site infection; they were managed conservatively. Modified skin bridge technique for IILD is an effective method to minimize flap necrosis without compromising the oncological safety. PMID- 27679782 TI - Adjuvant role of Pseudomonas flagellin for Acinetobacter baumannii biofilm associated protein. AB - AIM: To study immunogenicity of Pseudomonas N terminal flagellin as an adjuvant for Acinetobacter baumannii (A. baumannii) biofilm associated protein (Bap). METHODS: The N terminal flagellin gene was amplified. The pET28a (+) and polymerase chain reaction products were digested with HindIII and EcoR I. The ligation of N terminal flagellin into pET28a (?+) was performed using T4 DNA ligase and was then transformed into Escherichia coli BL21 (DE3) as a suitable expression host. pET28a (?+) vector harboring a conserved region of Bap from our previous work was used. The recombinant proteins were expressed, analyzed by SDS PAGE method and was purified by affinity chromatography with His-Tag residues followed by confirmation with western blotting. Mice were immunized with recombinant N terminal flagellin and Bap subunits. The immunized animals were intranasally (i.n) challenged with A. baumannii and Pseudomonas aeruginosa (P. aeruginosa). RESULTS: The flagellin enhanced the immunogenicity of Bap causing an increase in specific IgG titers in serum (P < 0.001). Internal organs, i.e., liver, lung and spleen of the Bap-Flagellin immunized group challenged with A. baumannii showed significantly lower bacterial load compared to the control group. The bacterial loads were studied in internal organs. A. baumannii infected immunized animals with Bap-Flagellin exhibited internal organs with minor bacterial load while P. aeruginosa PAO1 infected group showed heavy bacterial load of (4.3 +/- 0.12) * 10(6), (1.1 +/- 0.01) * 10(6) and (2.2 +/- 0.22) * 10(6) per gram of lungs, liver and spleen respectively. Bacterial loads were detected per gram of lungs, liver and spleen of the mice group immunized with Bap were (1.2 +/- 0.06) * 10(7), (11.1 +/- 0.041) * 10(5) and (3.6 +/- 0.42) * 10(6) respectively. In vivo neutralization assay indicated that all experimental mice groups, except for Flagellin administered group was significantly (P < 0.05) protected against A. baumannii. CONCLUSION: These results demonstrate that P. aeruginosa Flagellin as an adjuvant for Bap A. baumannii could be a useful model to evaluate new vaccine against A. baumannii. PMID- 27679783 TI - Prevalence of diabetes mellitus among children and adolescents in the district of Abidjan in Cote d'Ivoire: a population-based study. AB - BACKGROUND: World Health Organization has predicted a worldwide rise in the prevalence of diabetes mellitus. Cote d'Ivoire is not exempted as evidenced by such factors as obesity and sedentary life style amongst others. The objective of the study was to determine the prevalence of diabetes mellitus (DM) among children and adolescents in the district of Abidjan in Cote d'Ivoire. METHODS: A cross-sectional descriptive survey using a multi-stage sampling approach was conducted from March to April 2013. 1572 children and adolescents aged 02-19 years were surveyed in 687 randomly selected households in three municipalities. Capillary fasting glucose was performed in all subjects, and when abnormal was followed by an Oral Glucose Tolerance Test (OGTT). Definitions of Impaired Fasting Glucose (IFG) and DM (Diabetes Mellitus) were according to International Society for Paediatric and Adolescent Diabetes (ISPAD) Guidelines. RESULTS: The prevalence of DM and IFG were 0.4 % and 14.5 % respectively. There was no significant differences between patients with different glycemic status in terms of ethnicity/nationality (p = 0.98) or gender (0.079). In the rural areas, 565 (81.1 %) subjects were normoglycaemic and 132 (18.9 %) subjects hyperglycaemic while there were 773 (88.3 %) normoglycaemic subjects and 102 (11.7 %) hyperglycaemic subjects respectively from the urban areas of residence and this difference was statistically significant (p = 0.000). The prevalence of diabetes mellitus was identical (0.4 %) in the two age groups (2-9 years and 10-19 years). Seventy-seven (4.9 %) children who participated in the study had at least one diabetic parent. The proportion of participants with a diabetic father (59, 3.8. %) was twice the proportion with a diabetic mother (30,1.9 %) and this was statistically significant (p = 0.002). Only 10 out of 228 patients with IFG reported for the follow up OGTT and no impaired glucose tolerance was identified in these patients. CONCLUSION: The prevalence rate of DM among children and adolescents was 0.4 %. Nationwide awareness campaigns and prevention programmes about diabetes in childhood should be instituted and existing ones strengthened. Adequate commitment from the relevant stakeholders especially the country's ministry of health is also advocated to stem this looming epidemic. PMID- 27679784 TI - Cost Estimation of Road Traffic Injuries Among Iranian Motorcyclists Using the Willingness to Pay Method. AB - BACKGROUND: Motorcycle riders are amongst some of the most vulnerable road users. The burden of motorcycles injuries from low and middle income countries is under reported. OBJECTIVES: In this study, the cost of traffic injuries among motorcyclists was calculated using the willingness to pay (WTP) method in Iran in 2013. PATIENTS AND METHODS: In a cross-sectional study, 143 motorcyclists were randomly selected. The research questionnaire was prepared based on the standard WTP method [stated preference (SP), contingent value (CV) and revealed preference (RP) models] taking into consideration perceived risks, especially those in Iran. Data were collected by a scenario for motorcyclists. The criteria for inclusion in the study consisted of having at least a high school education and being in the age range of 18 - 65 years. The final analysis of the WTP data was performed using the Weibull model. RESULTS: The mean WTP was 888,110 IRR (Iranian Rial) among motorcyclists. The statistical value of life was estimated according to 4694 death cases as 3,146,225,350,943 IRR, which was equivalent to USD 104,874,178 based on the dollar free market rate of 30,000 IRR (purchasing power parity). The cost of injury was 6,903,839,551,000 IRR, equivalent to USD 230,127,985 (based upon 73,325 injured motorcyclists in 2013, a daily traffic volume of 311, and a daily payment of 12,110 IRR for 250 working days). In total, injury and death cases came to 10,050,094,901,943 IRR, equivalent to USD 335,003,163. Willingness to pay had a significant relationship with having experienced an accident, the length of the daily trip (in km), and helmet use (P < 0.001). CONCLUSIONS: Willingness to pay can be affected by experiencing an accident, the distance of the daily trip, and helmet use. The cost of traffic injuries among motorcyclists shows that this rate is much higher than the global average. Thus, expenditure should be made on effective initiatives such as the safety of motorcyclists. PMID- 27679785 TI - Surgical Treatment of Unstable Distal Radius Fractures With a Volar Variable Angle Locking Plate: Clinical and Radiological Outcomes. AB - BACKGROUND: Unstable distal end radius fractures are difficult to manage and so various treatment modalities have been described. The use of variable-angle locking plates is promoted for the management of these fractures. OBJECTIVES: This study aimed to evaluate the functional and radiological outcomes in unstable distal end radius fractures treated with variable-angle locking plates. PATIENTS AND METHODS: We reviewed 23 unstable distal end radius fractures that were treated at our institution with volar variable-angle locking plates. The mean age of the patients was 32.82 +/- 11.81 years (range 19 to 62) and the mean duration of follow-up was 11.04 +/- 2.47 months (range 6 to 15). All of the patients underwent open reduction and internal fixation with a variable-angle locking plate. Radiological parameters such as radial inclination, length, tilt, and ulnar variance were measured at six weeks and at the final follow-up. The functional evaluation was conducted by measuring the range of motion at the wrist joint as well as the grip strength. Gartland and Werley's demerit scoring system was used to assess the final outcome. RESULTS: There were two cases of superficial infection that responded to oral antibiotics. One patient had developed a hypertrophic scar, while another had carpal tunnel syndrome that was conservatively managed. There was a significant improvement in the functional indices from six weeks to the final follow-up, while the radiological parameters were maintained. According to Gartland and Werley, excellent results were reported in 65.2% cases, while good results were present in 35% cases. CONCLUSIONS: The use of variable-angle locking plates in treating unstable distal end radius fractures is associated with excellent to good functional outcomes with minimal complications. PMID- 27679786 TI - Bilateral Facial Paralysis Caused by Temporal Bone Fracture: A Case Report. AB - INTRODUCTION: Although bilateral facial nerve palsy is a rare condition, its etiology is more detectable than the unilateral type. A temporal bone fracture is one cause of bilateral facial nerve palsy, contributing in 3% of the cases. CASE PRESENTATION: Here, we report the case of a 35-year-old man complaining of bilateral incomplete eye closure, two weeks after a closed head injury caused by a motor vehicle accident. CONCLUSIONS: The high resolution computed tomography findings revealed a bilateral temporal bone fracture line, which extended to the fallopian canal. With regard to treatment, near complete recovery was obvious after two weeks of treatment with oral corticosteroids. Overall, bilateral facial palsy is hard to diagnose; therefore, clinical suspicion and the early detection of facial nerve injuries is necessary for good nerve recovery in temporal bone fractures. PMID- 27679787 TI - A Conservative Approach to the Management of a Dental Trauma for Immediate Natural Esthetics. AB - INTRODUCTION: The fracture of front teeth is one of the routine presentations of traumatic injuries. The treatment of a fractured tooth involving the pulp includes root canal therapy and post placement followed by core build-up or by the extraction of the fractured tooth if it is not restorable. CASE PRESENTATION: We report a case of an adult male who had traumatized both his maxillary central incisors following a blow experienced during domestic violence. He had lost a fractured fragment of the right central incisor, while the left incisor had complicated fractures with fragments retained attached to the soft tissue. Following radiovisiography (RVG), both incisors were conservatively treated in a single visit by reattachment and post and core techniques. CONCLUSIONS: The treatment reported for reattachment of the tooth fractures and post and core techniques are reasonably easy while providing immediate and lasting results in patients' regaining of social confidence and functionality. PMID- 27679788 TI - Trends in Road Traffic Deaths in Yazd, Iran, 2004 - 2010. AB - BACKGROUND: Road traffic deaths are a considerable public health problem and a major source of lost financial and human resources. Most mortality occurs in low- and middle-income countries. OBJECTIVES: This study aimed to measure road traffic fatality rates and years of lost life, and also to depict a view of trends in road traffic deaths from 2004 to 2010 in Yazd city, a province in central Iran. MATERIALS AND METHODS: This retrospective case study analyzed road traffic deaths that were classified under the V01 - V99 codes of the ICD-10 in Yazd province from March 2004 to March 2010, using data that were collected from the death registration system of the Yazd province health center. Cases were classified according to age, sex, time of year, and residence (urban vs. rural). Years of lost life and road fatality rate per 100,000 people were calculated. Data were analyzed using chi-square test and ANOVA with SPSS 16. RESULTS: During the seven year period of this study, 3,028 people in Yazd province died due to road traffic accidents (9.1% of total deaths in the province). Most deaths occurred among people aged 20-24 (15%), men (82.7%), and urban residents (82.6%). Total years of lost life (YLL) were 73,875 (60,337 and 13,489 in men and women, respectively). The road traffic fatality rate per 100,000 was 47.6 in 2004 and 37.6 in 2010. In the study period, the rate of traffic fatalities decreased for men (from 77.9 to 68.5) but this is not the case for women (from 14.8 to 19.2). Road traffic deaths peaked every summer. CONCLUSIONS: Despite the overall reduction trend, the road traffic fatality rate in Yazd province is still alarmingly high compared to national and global data. In addition, the female population shows increasing death rates. These findings can serve as a basis for health care professionals and policymakers to conduct preventive measures, especially during summer, and plan specifically for reducing fatalities in the female population. PMID- 27679789 TI - Hemoglobin-Based Oxygen Carrier for Traumatic Hemorrhagic Shock Treatment in a Jehovah's Witness. AB - INTRODUCTION: Treatment of severe hemorrhagic shock due to acute blood loss from traumatic injuries in a Jehovah's witness (JW) trauma patient is very challenging since hemostatic blood product resuscitation is limited by refusal of the transfusion of allogeneic blood products. CASE PRESENTATION: We describe a multifaceted approach to the clinical care of a severely anemic JW trauma patient including the early administration of a bovine hemoglobin-based oxygen carrier (HBOC) as a bridge to resolution of critical anemia (nadir hemoglobin 3.9 g/dL). Hemoglobin-based oxygen carrier infusions were used to supplement oxygen delivery until endogenous erythropoiesis could restore adequate red blood cell mass. Subsequent endogenous bone marrow recovery was supported by early administration of high-dose erythropoiesis-stimulating agents and iron supplementation. CONCLUSIONS: Early HBOC administration can be used in the treatment of severe hemorrhagic shock in trauma patients who refuse allogeneic blood. PMID- 27679790 TI - Road Traffic Related Injury Severity in Truck Drivers: A Prospective Medical and Technical Analysis of 582 Truck Crashes. AB - BACKGROUND: While cyclists and pedestrians are known to be at significant risk for severe injuries when exposed to road traffic accidents (RTA) involving trucks, little is known about RTA injury risk for truck drivers. OBJECTIVES: The aim of this study was to analyze the injury severity in truck drivers following RTAs. PATIENTS AND METHODS: Our local accident research unit prospectively documented 43000 RTAs involving 582 trucks between 2000 and 2011. Injury severity, including the abbreviated injury scale (AIS) and the maximum abbreviated injury scale (MAIS) were analyzed. Technical parameters (e.g. delta v, direction of impact), the location of accident, and its dependency on the road type were also taken into consideration. RESULTS: Thirteen percent (77/582) of truck drivers were injured. Extremities were found to be at highest risk of injury with the lower extremities (36x) being injured most severely (10x: AIS 2 and 3). Death occurred only after collisions with other trucks, and severity of injuries increased with an increased speed limit. The maximum abbreviated injury scale was higher in the crash opponents (56x MAIS >= 3) compared to the truck drivers (8x MAIS >= 3). Overall, 82% of the crash opponents were injured. CONCLUSIONS: The safety of truck drivers is assured by their vehicles, the consequence being that the risk of becoming injured is likely to be low. However, the legs especially are at high risk for severe injuries during RTAs. This probability increases in the instance of a collision with another truck. Nevertheless, in RTAs involving trucks and regular passenger vehicles, the other party is in higher risk of injury. PMID- 27679791 TI - Fear of Neighborhood Violence During Adolescence Predicts Development of Obesity a Decade Later: Gender Differences Among African Americans. AB - BACKGROUND: African American youth are more likely than other racial and ethnic groups to be obese. African American youth are also more likely to live in disadvantaged neighborhoods which increase their victimization, observation, and fear of violence. OBJECTIVES: This study tested if victimization, observation, and fear of violence in the neighborhood during adolescence predict trajectory of body mass index (BMI) in the 3rd decade of life in African Americans. PATIENTS AND METHODS: Data came from an 18-year community-based cohort. We used multi group latent growth curve modeling for data analysis, considering neighborhood violence at age 15 (i.e. victimization, observation, and fear) as predictors, and the linear slope for the average change in BMI from age 21 to 32 as the outcome, with age and socioeconomic status (i.e. intact family and parental employment) as covariates. RESULTS: Fear of neighborhood violence at age 15 was predictive of an increase in BMI from age 21 to 32 among female but not male African Americans. Victimization and observation of violence at age 15 did not predict BMI change from age 21 to 32 among female or male African Americans. CONCLUSIONS: Fear of neighborhood violence is a contributing factor to increased risk of obesity for female African American youth who live in disadvantaged areas. This finding has implications for prevention of obesity among African American women who are at highest risk for obesity in the United States. Initiatives that enhance neighborhood safety are critical strategies for obesity prevention among African American women. PMID- 27679792 TI - "The NET Outcome": Are Neutrophil Extracellular Traps of Any Relevance to the Pathophysiology of Autoimmune Disorders in Childhood? AB - Neutrophil extracellular trap (NET) formation represents a form of cell death distinct from apoptosis or necrosis, by which invading pathogens are simultaneously entangled and potentially eliminated. Increased NET formation is observed in systemic lupus erythematosus (SLE), rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated small vessel vasculitis, antiphospholipid antibody syndrome (APS), and psoriasis. NETs contribute to the pathogenesis of autoimmunity by exposing cryptic autoepitopes, which may facilitate the generation of autoantibodies, induce the production of interferons, and activate the complement cascade. In SLE, augmented disease activity and renal disease are associated with increased NET formation, so that NETs could serve as a marker for the monitoring of disease activity. NETs can additionally cause endothelial cell damage and death and stimulate inflammation in atheromatous plaques, adding to the accelerated atherosclerosis witnessed in autoimmune disease. Since NETs induce production of interferons, assessing the extent of NET formation might facilitate the prediction of IFN-alpha levels and identification of SLE patients with presumably better responses to anti-IFN-alpha therapies or other novel therapeutic concepts, such as N-acetyl-cysteine and inhibitors of DNase 1 and peptidylarginine deiminase 4 (PAD4), which also target NETs. In summary, the study of NETs provides a novel approach to the understanding of autoimmune disease pathogenesis in childhood and opens new vistas in the development of sensitive disease markers and targeted therapies. PMID- 27679793 TI - An Effective Model for Improving Global Health Nursing Competence. AB - This paper proposed an effective model for improving global health nursing competence among undergraduate students. A descriptive case study was conducted by evaluation of four implemented programs by the author. All programs were conducted with students majoring in nursing and healthcare, where the researcher was a program director, professor, or facilitator. These programs were analyzed in terms of students' needs assessment, program design, and implementation and evaluation factors. The concept and composition of global nursing competence, identified within previous studies, were deemed appropriate in all of our programs. Program composition varied from curricular to extracurricular domains. During the implementation phase, some of the programs included non-Korean students to improve cultural diversity and overcome language barriers. Qualitative and quantitative surveys were conducted to assess program efficacy. Data triangulation from students' reflective journals was examined. Additionally, students' awareness regarding changes within global health nursing, improved critical thinking, cultural understanding, and global leadership skills were investigated pre- and post-program implementation. The importance of identifying students' needs regarding global nursing competence when developing appropriate curricula is discussed. PMID- 27679794 TI - One Health Core Competency Domains. AB - The emergence of complex global challenges at the convergence of human, animal, and environmental health has catalyzed a movement supporting "One Health" approaches. Despite recognition of the importance of One Health approaches to address these complex challenges, little effort has been directed at identifying the seminal knowledge, skills, and attitudes necessary for individuals to successfully contribute to One Health efforts. Between 2008 and 2011, three groups independently embarked on separate initiatives to identify core competencies for professionals involved with One Health approaches. Core competencies were considered critically important for guiding curriculum development and continuing professional education, as they describe the knowledge, skills, and attitudes required to be effective. A workshop was convened in 2012 to synthesize the various strands of work on One Health competencies. Despite having different mandates, participants, and approaches, all of these initiatives identified similar core competency domains: management; communication and informatics; values and ethics; leadership; teams and collaboration; roles and responsibilities; and systems thinking. These core competency domains have been used to develop new continuing professional education programs for One Health professionals and help university curricula prepare new graduates to be able to contribute more effectively to One Health approaches. PMID- 27679795 TI - Taking Severe Acute Malnutrition Treatment Back to the Community: Practical Experiences from Nutrition Coverage Surveys. AB - The community-based management of acute malnutrition treatment model was introduced to respond to the limited coverage of the inpatient model. Yet until the introduction of quick and low-cost approaches to measuring coverage, its reach was unknown. Once the Coverage Monitoring Network (CMN) had been created to roll out the routine measurement of direct coverage estimates to implementers, they found that programs were reaching only a third of cases. The barriers found to be limiting coverage were the result of the limited perceived value, and therefore focus, on the community. Therefore, the Network used the coverage assessment methodology as a way to encourage implementers to engage more fully with the community. By introducing small changes to the project cycle, specifically a participatory approach to assessments, program design and implementation, the CMN has changed the way implementers engage with the community. Instead of viewing them as passive receivers of services, they have shifted their perspective to view them as service delivery partners. The process provides implementers with a deeper understanding of the context while allowing the community to better understand the program, its challenges, and the identification of solutions. The Network observed implementers from Ministries of Health, and non-governmental organizations, adjusted their understanding and approach to service provision, which is critical if we are to see sustainable increases in program coverage. These experiences show that there is an appetite from implementers in multiple contexts for these practical and simple tools for re-engaging the community. PMID- 27679796 TI - Contemporary Fatherhood and Its Consequences for Paternal Psychological Well being - A Cross-sectional Study of Fathers in Central Europe. AB - The emotional consequences of fatherhood are markedly conditional on the context in which fatherhood is lived out. This study examines the association between different contemporary forms of fatherhood and paternal psychological well-being. The data are from an anonymous online survey of 3615 biological fathers, stepfathers, adoptive fathers, and foster fathers across the German-speaking countries of Central Europe. First, a detailed characterization of the different existing family constellations is provided. Second, the consequences of these different contemporary forms of fatherhood for paternal psychological well-being are investigated. Fathers of all ages (M = 40.11, range: 19-72) with at least one child under the age of 18 were included in the present analysis (N = 2785). The presented findings demonstrate that a family structure consisting of two biological parents with biological children seems to be most beneficial to paternal well-being, while some other forms of contemporary fatherhood are associated with impaired well-being, independently of sociodemographic or relationship aspects. More specifically, a history of family separation in non residential biological fathers and blended-family fathers, and the concomitant loss of father-child contact, is shown to be particularly disadvantageous for the well-being of these fathers. Shared living arrangements, maintaining regular contact with biological children, or forming a new intact family could protect these fathers from negative outcomes. PMID- 27679797 TI - Capitation-Based Financing Hampers the Provision of Preventive Services in Primary Health Care. AB - Mortality caused by non-communicable diseases has been extremely high in Hungary, which can largely be attributed to not performed preventive examinations (PEs) at the level of primary health care (PHC). Both structures and financial incentives are lacking, which could support the provision of legally defined PEs. A Model Programme was launched in Hungary in 2012 to adapt the recommendations for PHC of the World Health Organization. A baseline survey was carried out to describe the occurrence of not performed PEs. A sample of 4320 adults representative for Hungary by age and gender was surveyed. Twelve PEs to be performed in PHC as specified by a governmental decree were investigated and quantified. Not performed PEs per person per year with 95% confidence intervals were computed for age, gender, and education strata. The number of not performed PEs for the entire adult population of Hungary was estimated and converted into expenses according to the official reimbursement costs of the National Health Insurance Fund. The rate of service use varied between 16.7 and 70.2%. There was no correlation between the unit price of examinations and service use (r = 0.356; p = 0.267). The rate of not performed PEs was not related to gender, but older age and lower education proved to be risk factors. The total number of not performed PEs was over 17 million in the country. Of the 31 million euros saved by not paying for PEs, the largest share was not spent on those in the lowest educational category. New preventive services offered in the reoriented PHC model program include systematic and scheduled health examination health promotion programs at community settings, risk assessment followed by individual or group care, and/or referral and chronic care. The Model Programme has created a pressure for collaborative work, consultation, and engagement at each level, from the GPs and health mediators up to the decision-making level. It channeled the population into preventive health services shown by the fact that more than 80% of the population in the intervention area has already participated in the health status assessment. PMID- 27679798 TI - The Role of Cardiac Side Population Cells in Cardiac Regeneration. AB - The heart has a limited ability to regenerate. It is important to identify therapeutic strategies that enhance cardiac regeneration in order to replace cardiomyocytes lost during the progression of heart failure. Cardiac progenitor cells are interesting targets for new regenerative therapies because they are self-renewing, multipotent cells located in the heart. Cardiac side population cells (cSPCs), the first cardiac progenitor cells identified in the adult heart, have the ability to differentiate into cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts. They become activated in response to cardiac injury and transplantation of cSPCs into the injured heart improves cardiac function. In this review, we will discuss the current literature on the progenitor cell properties and therapeutic potential of cSPCs. This body of work demonstrates the great promise cSPCs hold as targets for new regenerative strategies. PMID- 27679799 TI - Prognostic Value of Initial Assessment of Residual Hypoventilation Using Nocturnal Capnography in Mechanically Ventilated Neuromuscular Patients: A 5-Year Follow-up Study. AB - BACKGROUND: Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, and its efficiency is mostly assessed by daytime blood gases or nocturnal oxygen saturation monitoring (SpO2). Non-invasive transcutaneous measure of CO2 (TcCO2) allows to directly assess nocturnal hypercapnia and to detect residual hypoventilation with a higher sensitivity than SpO2. We aimed to compare the prognostic value of nocturnal SpO2 and TcCO2 in ventilated adult NMD patients. METHODS: All consecutive capno-oximetries performed between 2010 and 2011 in ventilated adult NMD patients were analyzed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Nocturnal hypoxemia and hypercapnia (using four different definitions) at baseline were compared in their ability to predict mortality and respiratory events requiring ICU admission during follow-up. RESULTS: Data from 55 patients were analyzed (median age 28 [interquartile range: 25-36.5] years; 71% Duchenne muscular dystrophy; vital capacity 12 [7-27]% of predicted; 51% tracheostomy). Capno-oxymetry showed hypoxemia in 14.5% and hypercapnia in 12.7-41.8%, according to the used definition. Over a follow-up lasting up to 5 years (median 4.0 [3.6-4.5] years), we observed 12 deaths and 20 respiratory events requiring ICU admission. Hypercapnia was significantly associated with the study outcomes, with TcCO2 > 49 mmHg during >=10% of the time being the best definition, while hypoxemia was not. CONCLUSION: Our data show for the first time that residual hypoventilation, assessed by capnometry, is significantly associated with negative outcomes in adult ventilated NMD patients, while oximetry is not. Accordingly, we suggest capnometry to be included in the systematic assessment of HMV efficiency in NMD patients. CLINICALTRIALSGOV IDENTIFIER: NCT02551406. PMID- 27679801 TI - Perspectives in Veterinary Pharmacology and Toxicology. PMID- 27679800 TI - Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions. AB - Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales. PMID- 27679802 TI - Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers. AB - Knowledge of protein structure provides essential insight into function, enhancing our understanding of diseases and enabling new treatment development. X ray crystallography has been used to solve the structures of more than 100 000 proteins; however, the vast majority represent long-lived states that do not capture the functional motions of these molecular machines. Reactions triggered by the addition of a ligand can be the most challenging to detect with crystallography because of the difficulty of synchronizing reactions to create detectable quantities of transient states. The development of X-ray free electron lasers (XFELs) and serial femtosecond crystallography (SFX) enables new approaches for solving protein structures following the rapid diffusion of ligands into micron sized protein crystals. Conformational changes occurring on millisecond timescales can be detected and time-resolved. Here, we describe a new XFEL injector which incorporates a microfluidic mixer to rapidly combine reactant and sample milliseconds before the sample reaches the X-ray beam. The mixing injector consists of bonded, concentric glass capillaries. The fabrication process, employing custom laser cut centering spacers and UV curable epoxy, ensures precise alignment of capillaries for repeatable, centered sample flow and dependable mixing. Crystal delivery capillaries are 50 or 75 MUm in diameter and can contain an integrated filter depending on the demands of the experiment. Reaction times can be varied from submillisecond to several hundred milliseconds. The injector features rapid and uniform mixing, low sample dilution, and high hit rates. It is fully compatible with existing SFX beamlines. PMID- 27679803 TI - Persistent nonequilibrium dynamics of the thermal energies in the spin and phonon systems of an antiferromagnet. AB - We present a temperature and fluence dependent Ultrafast X-Ray Diffraction study of a laser-heated antiferromagnetic dysprosium thin film. The loss of antiferromagnetic order is evidenced by a pronounced lattice contraction. We devise a method to determine the energy flow between the phonon and spin system from calibrated Bragg peak positions in thermal equilibrium. Reestablishing the magnetic order is much slower than the cooling of the lattice, especially around the Neel temperature. Despite the pronounced magnetostriction, the transfer of energy from the spin system to the phonons in Dy is slow after the spin-order is lost. PMID- 27679805 TI - Heartbeat: Do common genetic variants have a role in cardiovascular disease prediction? PMID- 27679804 TI - Light-induced structural changes in a monomeric bacteriophytochrome. AB - Phytochromes sense red light in plants and various microorganism. Light absorption causes structural changes within the protein, which alter its biochemical activity. Bacterial phytochromes are dimeric proteins, but the functional relevance of this arrangement remains unclear. Here, we use time resolved X-ray scattering to reveal the solution structural change of a monomeric variant of the photosensory core module of the phytochrome from Deinococcus radiodurans. The data reveal two motions, a bend and a twist of the PHY domain with respect to the chromophore-binding domains. Infrared spectroscopy shows the refolding of the PHY tongue. We conclude that a monomer of the phytochrome photosensory core is sufficient to perform the light-induced structural changes. This implies that allosteric cooperation with the other monomer is not needed for structural activation. The dimeric arrangement may instead be intrinsic to the biochemical output domains of bacterial phytochromes. PMID- 27679806 TI - Contemporary diagnosis and management of pulmonary hypertension. PMID- 27679807 TI - Fontan conversion is a dated approach to the failing Fontan. PMID- 27679808 TI - British Heart Foundation reflections on research competition 2016. PMID- 27679809 TI - Towards an ab initio theory for metal L-edge soft X-ray spectroscopy of molecular aggregates. AB - The Frenkel exciton model was adapted to describe X-ray absorption and resonant inelastic scattering spectra of polynuclear transition metal complexes by means of the restricted active space self-consistent field method. The proposed approach allows to substantially decrease the requirements on computational resources if compared to a full supermolecular quantum chemical treatment. This holds true, in particular, in cases where the dipole approximation to the electronic transition charge density can be applied. The computational protocol was applied to the calculation of X-ray spectra of the hemin complex, which forms dimers in aqueous solution. The aggregation effects were found to be comparable to the spectral alterations due to the replacement of the axial ligand by solvent molecules. PMID- 27679810 TI - Neural Correlates of the Time Marker for the Perception of Event Timing. AB - While sensory processing latency, inferred from the manual reaction time (RT), is substantially affected by diverse stimulus parameters, subjective temporal judgments are relatively accurate. The neural mechanisms underlying this timing perception remain obscure. Here, we measured human neural activity by magnetoencephalography while participants performed a simultaneity judgment task between the onset of random-dot coherent motion and a beep. In a separate session, participants performed an RT task for the same stimuli. We analyzed the relationship between neural activity evoked by motion onset and point of subjective simultaneity (PSS) or RT. The effect of motion coherence was smaller for PSS than RT, but changes in RT and PSS could both be predicted by the time at which an integrated sensory response crossed a threshold. The task differences could be ascribed to the lower threshold for PSS than for RT. In agreement with the psychophysical threshold difference, the participants reported longer delays in their motor response from the subjective motion onset for weaker stimuli. However, they could not judge the timing of stimuli weaker than the detection threshold. A possible interpretation of the present findings is that the brain assigns the time marker for timing perception prior to stimulus detection, but the time marker is available only after stimulus detection. PMID- 27679812 TI - Physiological, Behavioral, and Scientific Impact of Different Fluid Control Protocols in the Rhesus Macaque (Macaca mulatta). AB - Rhesus macaques are an important model in behavioral neuroscience due to their advanced cognitive abilities. To motivate animals to engage in complex tasks, fluid rewards, in conjunction with fluid control protocols, are often used. The impact of these protocols on animal welfare is controversial. We compared two fluid control protocols against a protocol providing free access to water and evaluated the impacts on physiological states of hydration, behavioral measures of welfare, and scientific output. Blood physiology did not significantly differ between any of the protocols, and urine measures were indicative of well functioning, healthy kidneys. Changes in behaviors were limited, the main one being an increase in motivation to drink on the stricter fluid control protocol, and improved task performance early in the week. Overall, fluid control protocols had little measurable impact on the welfare of rhesus macaques while ensuring that scientific data of high quality could be obtained. PMID- 27679811 TI - Adult Neurogenesis in the Female Mouse Hypothalamus: Estradiol and High-Fat Diet Alter the Generation of Newborn Neurons Expressing Estrogen Receptor alpha. AB - Estrogens and leptins act in the hypothalamus to maintain reproduction and energy homeostasis. Neurogenesis in the adult mammalian hypothalamus has been implicated in the regulation of energy homeostasis. Recently, high-fat diet (HFD) and estradiol (E2) have been shown to alter cell proliferation and the number of newborn leptin-responsive neurons in the hypothalamus of adult female mice. The current study tested the hypothesis that new cells expressing estrogen receptor alpha (ERalpha) are generated in the arcuate nucleus (ARC) and the ventromedial nucleus of the hypothalamus (VMH) of the adult female mouse, hypothalamic regions that are critical in energy homeostasis. Adult mice were ovariectomized and implanted with capsules containing E2 or oil. Within each hormone group, mice were fed an HFD or standard chow for 6 weeks and treated with BrdU to label new cells. Newborn cells that respond to estrogens were identified in the ARC and VMH, of which a subpopulation was leptin sensitive, indicating that the subpopulation consists of neurons. Moreover, there was an interaction between diet and hormone with an effect on the number of these newborn ERalpha-expressing neurons that respond to leptin. Regardless of hormone treatment, HFD increased the number of ERalpha-expressing cells in the ARC and VMH. E2 decreased hypothalamic fibroblast growth factor 10 (Fgf10) gene expression in HFD mice, suggesting a role for Fgf10 in E2 effects on neurogenesis. These findings of newly created estrogen-responsive neurons in the adult brain provide a novel mechanism by which estrogens can act in the hypothalamus to regulate energy homeostasis in females. PMID- 27679813 TI - Using a Semi-Automated Strategy to Develop Multi-Compartment Models That Predict Biophysical Properties of Interneuron-Specific 3 (IS3) Cells in Hippocampus. AB - Determining how intrinsic cellular properties govern and modulate neuronal input output processing is a critical endeavor for understanding microcircuit functions in the brain. However, lack of cellular specifics and nonlinear interactions prevent experiments alone from achieving this. Building and using cellular models is essential in these efforts. We focus on uncovering the intrinsic properties of mus musculus hippocampal type 3 interneuron-specific (IS3) cells, a cell type that makes GABAergic synapses onto specific interneuron types, but not pyramidal cells. While IS3 cell morphology and synaptic output have been examined, their voltage-gated ion channel profile and distribution remain unknown. We combined whole-cell patch-clamp recordings and two-photon dendritic calcium imaging to examine IS3 cell membrane and dendritic properties. Using these data as a target reference, we developed a semi-automated strategy to obtain multi-compartment models for a cell type with unknown intrinsic properties. Our approach is based on generating populations of models to capture determined features of the experimental data, each of which possesses unique combinations of channel types and conductance values. From these populations, we chose models that most closely resembled the experimental data. We used these models to examine the impact of specific ion channel combinations on spike generation. Our models predict that fast delayed rectifier currents should be present in soma and proximal dendrites, and this is confirmed using immunohistochemistry. Further, without A-type potassium currents in the dendrites, spike generation is facilitated at more distal synaptic input locations. Our models will help to determine the functional role of IS3 cells in hippocampal microcircuits. PMID- 27679814 TI - Gain- and Loss-Related Brain Activation Are Associated with Information Search Differences in Risky Gambles: An fMRI and Eye-Tracking Study. AB - People differ in the way they approach and handle choices with unsure outcomes. In this study, we demonstrate that individual differences in the neural processing of gains and losses relates to attentional differences in the way individuals search for information in gambles. Fifty subjects participated in two independent experiments. Participants first completed an fMRI experiment involving financial gains and losses. Subsequently, they performed an eye tracking experiment on binary choices between risky gambles, each displaying monetary outcomes and their respective probabilities. We find that individual differences in gain and loss processing relate to attention distribution. Individuals with a stronger reaction to gains in the ventromedial prefrontal cortex paid more attention to monetary amounts, while a stronger reaction in the ventral striatum to losses was correlated with an increased attention to probabilities. Reaction in the posterior cingulate cortex to losses was also found to correlate with an increased attention to probabilities. Our data show that individual differences in brain activity and differences in information search processes are closely linked. PMID- 27679815 TI - A pi-gel scaffold for assembling fullerene to photoconducting supramolecular rods. AB - Nonequilibrium self-assembly of molecules holds a huge prospect as a tool for obtaining new-generation materials for future applications. Crystallization of neutral molecules within a supramolecular gel matrix is one example in which two nonequilibrium processes occur orthogonal to each other. On the other hand, electronically interacting donor-acceptor two-component systems are expected to form phase-miscible hybrid systems. Contrary to the expectation, we report the behavior of a pi-gel, derived from oligo(p-phenylenevinylene), OPVA, as a scaffold for the phase separation and crystallization of fullerene (C60) to supramolecular rods with increased transient photoconductivity (phi?MUmax = 2.4 * 10-4 cm2 V-1 s-1). The C60 supramolecular rods in the pi-gel medium exhibited high photocurrent in comparison to C60 loaded in a non-pi-gel medium. This finding provides an opportunity for large-scale preparation of micrometer-sized photoconducting rods of fullerenes for device application. PMID- 27679818 TI - Belousov-Zhabotinsky autonomic hydrogel composites: Regulating waves via asymmetry. AB - Belousov-Zhabotinsky (BZ) autonomic hydrogel composites contain active nodes of immobilized catalyst (Ru) encased within a nonactive matrix. Designing functional hierarchies of chemical and mechanical communication between these nodes enables applications ranging from encryption, sensors, and mechanochemical actuators to artificial skin. However, robust design rules and verification of computational models are challenged by insufficient understanding of the relative importance of local (molecular) heterogeneities, active node shape, and embedment geometry on transient and steady-state behavior. We demonstrate the predominance of asymmetric embedment and node shape in low-strain, BZ-gelatin composites and correlate behavior with gradients in BZ reactants. Asymmetric embedment of square and rectangular nodes results in directional steady-state waves that initiate at the embedded edge and propagate toward the free edge. In contrast, symmetric embedment does not produce preferential wave propagation because of a lack of diffusion gradient across the catalyzed region. The initiation at the embedded edge is correlated with bromide absorption by the inactive matrix, which locally elevates the bromate concentration required for catalyst oxidation. The competition between embedment asymmetry and node geometry was used to demonstrate a repeatable switch in wave direction that functions as a signal delay. Furthermore, signal propagation in or out of the composite was demonstrated via embedment asymmetry and relative dimensions of a T-shaped active network node. Overall, structural asymmetry provides a robust approach to controlling initiation and orientation of chemical-mechanical communication within composite BZ gels. PMID- 27679816 TI - Native phasing of x-ray free-electron laser data for a G protein-coupled receptor. AB - Serial femtosecond crystallography (SFX) takes advantage of extremely bright and ultrashort pulses produced by x-ray free-electron lasers (XFELs), allowing for the collection of high-resolution diffraction intensities from micrometer-sized crystals at room temperature with minimal radiation damage, using the principle of "diffraction-before-destruction." However, de novo structure factor phase determination using XFELs has been difficult so far. We demonstrate the ability to solve the crystallographic phase problem for SFX data collected with an XFEL using the anomalous signal from native sulfur atoms, leading to a bias-free room temperature structure of the human A2A adenosine receptor at 1.9 A resolution. The advancement was made possible by recent improvements in SFX data analysis and the design of injectors and delivery media for streaming hydrated microcrystals. This general method should accelerate structural studies of novel difficult-to crystallize macromolecules and their complexes. PMID- 27679819 TI - Geodetic measurements reveal similarities between post-Last Glacial Maximum and present-day mass loss from the Greenland ice sheet. AB - Accurate quantification of the millennial-scale mass balance of the Greenland ice sheet (GrIS) and its contribution to global sea-level rise remain challenging because of sparse in situ observations in key regions. Glacial isostatic adjustment (GIA) is the ongoing response of the solid Earth to ice and ocean load changes occurring since the Last Glacial Maximum (LGM; ~21 thousand years ago) and may be used to constrain the GrIS deglaciation history. We use data from the Greenland Global Positioning System network to directly measure GIA and estimate basin-wide mass changes since the LGM. Unpredicted, large GIA uplift rates of +12 mm/year are found in southeast Greenland. These rates are due to low upper mantle viscosity in the region, from when Greenland passed over the Iceland hot spot about 40 million years ago. This region of concentrated soft rheology has a profound influence on reconstructing the deglaciation history of Greenland. We reevaluate the evolution of the GrIS since LGM and obtain a loss of 1.5-m sea level equivalent from the northwest and southeast. These same sectors are dominating modern mass loss. We suggest that the present destabilization of these marine-based sectors may increase sea level for centuries to come. Our new deglaciation history and GIA uplift estimates suggest that studies that use the Gravity Recovery and Climate Experiment satellite mission to infer present-day changes in the GrIS may have erroneously corrected for GIA and underestimated the mass loss by about 20 gigatons/year. PMID- 27679817 TI - Single-neuron and genetic correlates of autistic behavior in macaque. AB - Atypical neurodevelopment in autism spectrum disorder is a mystery, defying explanation despite increasing attention. We report on a Japanese macaque that spontaneously exhibited autistic traits, namely, impaired social ability as well as restricted and repetitive behaviors, along with our single-neuron and genomic analyses. Its social ability was measured in a turn-taking task, where two monkeys monitor each other's actions for adaptive behavioral planning. In its brain, the medial frontal neurons responding to others' actions, abundant in the controls, were almost nonexistent. In its genes, whole-exome sequencing and copy number variation analyses identified rare coding variants linked to human neuropsychiatric disorders in 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) and adenosine triphosphate (ATP)-binding cassette subfamily A13 (ABCA13). This combination of systems neuroscience and cognitive genomics in macaques suggests a new, phenotype-to-genotype approach to studying mental disorders. PMID- 27679821 TI - From damage to discovery via virtual unwrapping: Reading the scroll from En-Gedi. AB - Computer imaging techniques are commonly used to preserve and share readable manuscripts, but capturing writing locked away in ancient, deteriorated documents poses an entirely different challenge. This software pipeline-referred to as "virtual unwrapping"-allows textual artifacts to be read completely and noninvasively. The systematic digital analysis of the extremely fragile En-Gedi scroll (the oldest Pentateuchal scroll in Hebrew outside of the Dead Sea Scrolls) reveals the writing hidden on its untouchable, disintegrating sheets. Our approach for recovering substantial ink-based text from a damaged object results in readable columns at such high quality that serious critical textual analysis can occur. Hence, this work creates a new pathway for subsequent textual discoveries buried within the confines of damaged materials. PMID- 27679822 TI - Additive lattice kirigami. AB - Kirigami uses bending, folding, cutting, and pasting to create complex three dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes. PMID- 27679820 TI - Mechanical assembly of complex, 3D mesostructures from releasable multilayers of advanced materials. AB - Capabilities for assembly of three-dimensional (3D) micro/nanostructures in advanced materials have important implications across a broad range of application areas, reaching nearly every class of microsystem technology. Approaches that rely on the controlled, compressive buckling of 2D precursors are promising because of their demonstrated compatibility with the most sophisticated planar technologies, where materials include inorganic semiconductors, polymers, metals, and various heterogeneous combinations, spanning length scales from submicrometer to centimeter dimensions. We introduce a set of fabrication techniques and design concepts that bypass certain constraints set by the underlying physics and geometrical properties of the assembly processes associated with the original versions of these methods. In particular, the use of releasable, multilayer 2D precursors provides access to complex 3D topologies, including dense architectures with nested layouts, controlled points of entanglement, and other previously unobtainable layouts. Furthermore, the simultaneous, coordinated assembly of additional structures can enhance the structural stability and drive the motion of extended features in these systems. The resulting 3D mesostructures, demonstrated in a diverse set of more than 40 different examples with feature sizes from micrometers to centimeters, offer unique possibilities in device design. A 3D spiral inductor for near-field communication represents an example where these ideas enable enhanced quality (Q) factors and broader working angles compared to those of conventional 2D counterparts. PMID- 27679824 TI - Analysis of ovarian reserve markers (AMH, FSH, AFC) in different age strata in IVF/ICSI patients. AB - BACKGROUND: The predictive roles of follicle stimulating hormone (FSH), anti mullerian hormone (AMH) and antral follicle count (AFC) as ovarian reserve markers in women with different age groups are not established well. OBJECTIVE: This study compares the value of FSH, AMH and AFC at the time of in vitro fertilization (IVF) treatment in different age groups. MATERIALS AND METHODS: In this cross-sectional study, 103 women aged 20-43 years candidates for IVF/ICSI cycle were recruited. FSH, AMH and AFC on day 3 of menstrual cycle were measured. The relationship of these measured markers with outcome variables (oocytes number, number of frozen/fresh embryo and chemical and clinical pregnancy) was assessed in different age groups (i.e. 20-32, 33-37 and 38-43 years). RESULTS: our results show that age was correlated with clinical pregnancy, oocyte count and fresh and frozen embryo (p<0.001). AMH, AFC and FSH were not correlated with clinical or chemical pregnancy at total population or age subgroups except the significant correlation of AFC with clinical pregnancy at 33-37 years old group. AFC was correlated with oocyte count and the number of fresh and frozen embryos in the ages group 20-32 years. In this age group, AMH was correlated with fresh and frozen embryos. AMH, AFC and FSH were correlated with oocyte count and the number of fresh embryos in age group 33-37 years. AMH was correlated with oocyte count and the number of fresh embryos in 38-43 years old group. CONCLUSION: We concluded that the age is the superior predictor of IVF outcome and AMH and AFC are variable predicting markers of ovarian reserve in different age groups. PMID- 27679823 TI - PCOS women show significantly higher homocysteine level, independent to glucose and E2 level. AB - BACKGROUND: It is reasonable to think that some biochemical characteristics of follicular fluid (FF) surrounding the oocyte may play a critical role in determining the quality of oocyte and the subsequent potential needed to achieve fertilization and embryo development. OBJECTIVE: This study was carried out to evaluate the levels of FF homocysteine (Hcy) in IVF candidate polycystic ovary syndrome (PCOS) women and any relationships with FF glucose and estradiol (E2) levels. MATERIALS AND METHODS: In this case control study which was performed in Dr. Tizro Day Care and IVF Center 70 infertile patients were enrolled in two groups: comprising 35 PCOS and 35 non PCOS women. Long protocol was performed for all patients. FF Hcy, glucose and E2 levels were analyzed at the time of oocyte retrieval. RESULTS: It was observed that FF Hcy level was significantly higher in PCOS patients compared with non PCOSs (p<0.01). Observations demonstrated that in PCOS group, the Hcy level increased independent to E2, glucose levels, BMI and age, while the PCOS group showed significantly higher BMI compared with non-PCOS group (p=0.03). However, no significant differences were revealed between groups for FF glucose and E2 levels. CONCLUSION: Present data showed that although FF glucose and E2 levels were constant in PCOS and non PCOS patients, but the FF Hcy levels in PCOS were significantly increased (p=0.01). PMID- 27679825 TI - The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS. AB - BACKGROUND: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. OBJECTIVE: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. MATERIALS AND METHODS: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. RESULTS: The pregnancy outcomes were not significantly different between two groups (p=0.224). CONCLUSION: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes. PMID- 27679826 TI - Alternation of apoptotic and implanting genes expression of mouse embryos after re-vitrification. AB - BACKGROUND: Nowadays, oocytes and embryos vitrification has become a routine technique. Based on clinical judgment, re-vitrification maybe required. But little is known about re-vitrification impact on genes expression. OBJECTIVE: The impact of re-vitrification on apoptotic and implanting genes, Bax, Bcl-2 and ErbB4, at compaction stage embryos were evaluated in this study. MATERIALS AND METHODS: In this experimental study, 8 cell embryos (n=240) were collected from female mature mice, 60-62 hr post HCG injection. The embryos were divided randomly to 3 groups included: fresh (n=80), vitrified at 8 cell stage (n=80), vitrified at 8 cell stage thawed and re-vitrified at compaction stage (n=80). Embryos were vitrified by using cryolock, (open system) described by Kuwayama. Q PCR was used to examine the expression of Bax, Bcl2 ErbB4 genes in derived blastocysts. RESULTS: Our result showed that expanded blastocyst rate was similar between vitrified and re-vitrified groups, while re-vitrified embryos showed significant decrease in expanded blastocyst rate comparing with fresh embryos (p=0.03). In addition, significant difference was observed on apoptotic gene expression when comparing re-vitrified and fresh embryos (p=0.004), however expression of Bax and Bcl-2 (apoptotic) genes didn't demonstrate a significant difference between re-vitrified and vitrified groups. The expression rate of ErbB4, an implantation gene was decreased in re-vitrified embryos comparing with fresh embryos (p=0.003), but it was similar between re-vitrified and vitrified embryos. CONCLUSION: Re-vitrification can alter the expression of Bax, Bcl-2 and ErbB4 genes and developmental rate of mouse embryos in compaction stage. PMID- 27679827 TI - Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats. AB - BACKGROUND: Diabetes is the most common endocrine disease. It has adverse effects on male reproductive function. Royal Jelly (RJ) has antioxidant and anti-diabetic effects and show protective effects against diabetes. OBJECTIVE: This study was conducted to evaluate the effect of RJ on histopathological alterations of the testicular tissue in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: In this experimental study, 28 adult Wistar rats were randomly divided into control (C), royal jelly (R), diabetic (D) and RJ-treated diabetic (D+R) groups. Diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg body weight (BW). The rats from the R and D+R groups received daily RJ (100 mg/kg BW) for 6 wks orally. Hematoxylin-Eosin staining was used to analyze histopathological changes including: tunica albuginea thickness (TAT), seminiferous tubules diameter (STsD), Johnsen's score, tubular differentiation index (TDI), spermiogenesis index (SPI), Sertoli cell index (SCI), meiotic index (MI), and mononuclear immune cells (MICs) in testes. The antioxidant status was examined by evaluating testicular levels of ferric reducing antioxidant power (FRAP) and catalase (CAT) activity. RESULTS: Histological results of the testis from diabetic rats showed significant decrease in STsD, Johnsen's score, TDI, SPI, SCI and MI, and significant increase in TAT and MICs, while administration of RJ significantly reverted these changes (p<0.05). RJ treatment markedly increased activity of CAT and FRAP. There were significant differences in FRAP levels among C (13.0+/-0.5), RJ (13.4+/-0.3), D (7.8+/-0.6) and D+R (12.4+/-0.7) groups (p<0.05). CONCLUSION: RJ improved diabetes-induced impairment in testis, probably through its antioxidant property. PMID- 27679828 TI - Mutation analysis of exon1 of bone morphogenetic protein-15 gene in Iranian patients with polycystic ovarian syndrome. AB - BACKGROUND: With the prevalence of 6-10%, polycystic ovarian syndrome (PCOS) is considered the most common endocrinological disorder affecting women in their reproductive age. It has been suggested that genetic factors participate in the development of PCOS. Follicular development has been considered as one of the impaired processes in PCOS. Bone morphogenetic protein-15 (BMP-15) gene is a candidate gene in follicular development and its variants may play role in pathogenesis of PCOS. OBJECTIVE: To investigate whether BMP-15 gene mutations are present in Iranian women with PCOS. MATERIALS AND METHODS: In this cross sectional study 5 ml venous blood samples was taken from 70 PCOS women referring to Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran, between January to December 2014. Genomic DNA was extracted from the blood sample by salting out method. Then a set of PCR reactions for exon1 of BMP-15 gene was performed using specific primers followed by genotyping with direct sequencing. RESULTS: Two different polymorphisms were found in the gene under study. In total 20 patients (28.6%) were heterozygote (C/G), and 2 patients (2.86%) were homozygous (G/G) for c.-9C>G in 5'UTR promoter region of BMP-15 gene (rs3810682). In addition, in the coding region of exon1, three patients (4.3%) were heterozygote (G/A) for c.A308G (rs41308602). Two PCOS patients (2.86%) appeared to have both c.-9C>G (C/G) and c.A308G (G/A) variants simultaneously. CONCLUSION: Our research detected two polymorphisms of BMP-15 gene among PCOS patients, indicating that even though it cannot be concluded that variants of BMP-15 gene are the principal cause of polycystic ovarian syndrome; they could be involved in pathogenic process in development of PCOS. PMID- 27679829 TI - The influence of ginger (Zingiber officinale) on human sperm quality and DNA fragmentation: A double-blind randomized clinical trial. AB - BACKGROUND: Although the effectiveness of ginger as an antioxidant agent has been exploited, little human research has been conducted on its activity on male reproductive functions. OBJECTIVE: This study was designed to investigate the effects of ginger (Zingiber officinale) on sperm DNA fragmentation (SDF) in infertile men. MATERIALS AND METHODS: This randomized double-blind, placebo controlled trial with a 1:1 allocation was performed on 100 infertility treatment candidates who were admitted to Royan Institute for Reproductive Biomedicine, Tehran, Iran. Patients were randomly assigned to receive one of two treatments: ginger and placebo. Patients were given a 3-month oral treatment (members received capsules containing 250 mg of ginger powder twice a day in ginger and a placebo in other group). Before and after treatment, standardized semen samples were obtained to determine sperm concentration, motility, and SDF according to World Health Organization. RESULTS: There was no significant difference between two groups regarding SDF at baseline (53.48. 95%CI: 37.95-69.02) in cases and (56.75, 95%CI: 40.01-73.5) in controls. The average positive percentage of SDF in patients receiving ginger (17.77, 95%CI: 6.16-29.39) was lower compared with placebo (40.54, 95%CI: 23.94-57.13) after three month of treatment (p=0.02). In multivariate analysis, SDF was significantly lower in patients receiving ginger compared with placebo (mean difference: 3.21, 95%CI: 0.78-5.63, p=0.009). There were no significant differences between two groups regarding to semen parameters. CONCLUSION: The present study has demonstrated that ginger in a controlled study of efficacy was effective in decreasing SDF in infertile men. PMID- 27679835 TI - The challenge of diagnosing hypertrophic cardiomyopathy in patients of African descent. PMID- 27679830 TI - Kallmann syndrome and deafness: an uncommon combination: A case report and a literature review. AB - BACKGROUND: Kallmann syndrome (Kal S) is an isolated form of hypogonadotrophic hypogonadism in combination with a defect in smell sensation. Depending on the genetic form of the disease, a number of non-reproductive, non-olfactory abnormalities may also be existent. In the present report, we describe a male with Kal S associated with hearing loss, and the successful treatment of his sexual and reproductive defects. CASE: A 23-year-old Caucasian man presented with a lifelong lack of erection and ejaculation. The patient reported also anosmia combined with loss of hearing ability. A diagnostic work-up identified the presence of Kal S associated with sensorineural hearing loss. Administration of gonadotrophins regained the erection and a viable-sperm containing ejaculation. CONCLUSION: Lack of erection and ejaculation are important components of delayed puberty which could lead to diagnosis of Kal S. The existence of a hearing impairment in the reported patient makes the recommendation to screen the hearing ability in Kal S of utmost importance. PMID- 27679836 TI - Comparison of hypertrophic cardiomyopathy in Afro-Caribbean versus white patients in the UK. AB - BACKGROUND: This study investigated the influence of African/Afro-Caribbean (black) ethnicity on the clinical profile and outcomes in hypertrophic cardiomyopathy (HCM). METHODS: 425 consecutive patients with HCM (163 black and 262 Caucasians (white); mean age 52.5+/-16.6 years) were assessed at three cardiomyopathy centres. Repeat assessments were performed every 6-12 months and mean follow-up was 4.3+/-3.0 years. The primary outcome was a composite of cardiovascular death, cardiac arrest or appropriate device therapy. RESULTS: A fortuitous diagnosis of HCM was more commonly made in black compared with white patients (31.3% vs 19.1%, p=0.004). An abnormal ECG at presentation was more frequent in black patients (98.2% vs 90.5%, p=0.002), with T-wave inversion being a common feature (91.4% vs 73.0%, p<0.001). Asymmetric septal hypertrophy was the predominant pattern in both ethnic groups; however, apical (22.2% vs 10.7%, p<0.001) and concentric (9.3% vs 1.5%, p<0.001) patterns were more prevalent in black patients. Hypertension was more frequent in black patients (58.3% vs 31.7%, p<0.001). There were no ethnic differences in risk factor profile or primary outcome. Independent predictors of the primary outcome were non-sustained ventricular tachycardia (HR 6.03, 95% CI 3.06 to 11.91, p<=0.001) and hypertension at presentation (HR 2.02, 95% CI 1.05 to 3.88, p=0.036), with an additive effect. CONCLUSION: Black ethnicity is an important determinant of the phenotypic expression of HCM but does not adversely affect outcomes. Apical and concentric hypertrophy are common in black patients and may hinder the identification of HCM in this cohort. Hypertension has an adverse effect on outcome, irrespective of ethnicity. PMID- 27679837 TI - Opinion: Big data has big potential for applications to climate change adaptation. PMID- 27679840 TI - Identifying and Prioritizing Diseases Important for Detection in Adult Hearing Health Care. AB - PURPOSE: The purpose of this research note is to identify and prioritize diseases important for detection in adult hearing health care delivery systems. METHOD: Through literature review and expert consultation, the authors identified 195 diseases likely to occur in adults complaining of hearing loss. Five neurotologists rated the importance of disease on 3 dimensions related to the necessity of detection prior to adult hearing aid fitting. RESULTS: Ratings of adverse health consequences, diagnostic difficulty, and presence of nonotologic symptoms associated with these diseases resulted in the identification of 104 diseases potentially important for detection prior to adult hearing aid fitting. CONCLUSIONS: Current and evolving health care delivery systems, including direct to-consumer sales, involve inconsistent means of disease detection vigilance prior to device fitting. The first steps in determining the safety of these different delivery methods are to identify and prioritize which diseases present the greatest risk for poor health outcomes and, thus, should be detected in hearing health care delivery systems. Here the authors have developed a novel multidimensional rating system to rank disease importance. The rankings can be used to evaluate the effectiveness of alternative detection methods and to inform public health policy. The authors are currently using this information to validate a consumer questionnaire designed to accurately identify when pre- fitting medical evaluations should be required for hearing aid patients. PMID- 27679839 TI - Social Networking Services-Based Communicative Care for Patients with Diabetes Mellitus in Korea. AB - OBJECTIVES: Social networking services (SNS)-based online communities are good examples of improving quality of care by incorporating information technology into medicine. Therefore, we created an SNS-based community care webpage for communication among patients with diabetes mellitus (DM). We aimed to identify what diabetic patients wanted to know and were interested in by analyzing their posts and classified content in which users were interested. METHODS: As opposed to the existing physician-focused health information websites, we built a patient focused experience exchange website, "I love insulin (http://www.iloveinsulin.co.kr)." The DM communication webpage was divided into "My Web-Chart," "My community-free board," and "Life & Health." The contents analysis targeted users' postings, and replies were classified by theme from May 2012 to June 2013. The data included number of questions asked, answers, and question-to-answer (QA) ratio in each category. RESULTS: A total of 264 patients registered on the "I Love Insulin" website. The most frequent topic of posts classified as questions were about diabetes itself (23%), diet (22%), and glucose levels (19%). Conversely, most answers and information provided by users were about daily life with no relationship to diabetes mellitus (54%). While there were many questions about diet, there were very few answers (2%). Whereas there was much provision of knowledge about general DM, sharing diet information was rare. The ratios of answers to questions on diet (ratio=0.059, 1/17), glucose level (ratio=0.067, 1/15), insulin regulation (ratio=0.222, 2/9) and webpage (ratio=0.167, 1/6) were significantly low compared to DM itself (all p < 0.001). DISCUSSION: Patients in Korea with DM tend to have insufficient knowledge about diet and insulin regulation; continuously providing diet and insulin regulation information are desirable. It is hoped that the patients would be motivated to participate actively by "knowledge sharing." Through this process, patients learn about their diseases not from the physicians but from among themselves. PMID- 27679841 TI - Picture Exchange Communication System and Pals: A Peer-Mediated Augmentative and Alternative Communication Intervention for Minimally Verbal Preschoolers With Autism. AB - Purpose: This study was conducted to investigate the effectiveness of a social intervention that integrates peer-mediated approaches and the Picture Exchange Communication System (PECS). Method: Effects were evaluated using a series of A-B designs replicated across 4 children with severe autism and limited verbal skills. Seven peers without disabilities were trained to use PECS and facilitative social skills. Measures of changes included rates of communication behaviors, modes, functions, and engagement. Results: Outcomes revealed an intervention effect for 1 child with autism, and this effect was replicated across 3 other children. All children improved in peer-directed communication, with greater increases for 2 children during snack time. For each child with autism, the primary communication behavior was to initiate with picture symbols to request; the peer's primary communication was to respond. Two children increased communicative functions to comment and to share, and all 4 children showed improved social engagement. All peers increased their communication with the children with autism. Conclusions: These findings add to the limited research on the benefits of teaching typically developing peers to be responsive listeners to preschoolers with autism by learning to use PECS. These results invite further investigation of teaching peers other augmentative and alternative communication approaches and how to increase children's communication with peers for different purposes. PMID- 27679843 TI - Telling Tales: Personal Event Narratives and Life Stories. AB - Purpose: Speech-language pathologists know much more about children's development of fictional narratives than they do about children's development of personal narratives and the role these personal narratives play in academic success, social-emotional development, and self-regulation. The purpose of this tutorial is to provide clinicians with strategies for assessing and developing children's and adolescents' personal narratives. Method: This tutorial reviews the literature on (a) the development of autobiographical event narratives and life stories, (b) factors that contribute to development of these genres, (c) the importance of these genres for the development of sense of self-identity and self regulation, (d) deficits in personal narrative genres, and (e) strategies for eliciting and assessing event narratives and life stories. Implications: To promote development of personal event narratives and life stories, speech language pathologists can help clients retrieve information about interesting events, provide experiences worthy of narrating, and draw upon published narratives to serve as model texts. Clinicians can also address four interrelated processes in intervention: reminiscing, reflecting, making coherent connections, and signaling the plot structure. Furthermore, they can activate metacognitive awareness of how evaluations of experiences, coherence, and plot structure are signaled in well-formed personal event narratives and life stories. PMID- 27679842 TI - Speech Movement Measures as Markers of Bulbar Disease in Amyotrophic Lateral Sclerosis. AB - Purpose: The goal of this study was to identify the effects of amyotrophic lateral sclerosis (ALS) on tongue and jaw control, both cross-sectionally and longitudinally. The data were examined in the context of their utility as a diagnostic marker of bulbar disease. Method: Tongue and jaw movements were recorded cross-sectionally (n = 33 individuals with ALS, 13 controls) and longitudinally (n = 10 individuals with ALS) using a three-dimensional electromagnetic articulography system during the production of the sentence Buy Bobby a puppy. The movements were examined for evidence of changes in size, speed, and duration and with respect to disease severity and time in the study. Results: Maximum speed of tongue movements and movement durations were significantly different only at an advanced stage of bulbar ALS compared with the healthy control group. The longitudinal analysis revealed a reduction in tongue movement size and speed with time at early stages of disease, which was not seen cross-sectionally. As speaking rate declined, tongue movements decreased in maximum speed, whereas jaw movements increased in maximum speed. Conclusions: Longitudinal analyses of sentence-level kinematic data show their sensitivity to early bulbar impairment. A change in articulatory kinematics can serve as a useful diagnostic marker for bulbar ALS and to track bulbar disease progression in a clinical setting. PMID- 27679844 TI - Metal halide perovskite light emitters. AB - Twenty years after layer-type metal halide perovskites were successfully developed, 3D metal halide perovskites (shortly, perovskites) were recently rediscovered and are attracting multidisciplinary interest from physicists, chemists, and material engineers. Perovskites have a crystal structure composed of five atoms per unit cell (ABX3) with cation A positioned at a corner, metal cation B at the center, and halide anion X at the center of six planes and unique optoelectronic properties determined by the crystal structure. Because of very narrow spectra (full width at half-maximum <=20 nm), which are insensitive to the crystallite/grain/particle dimension and wide wavelength range (400 nm <= lambda <= 780 nm), perovskites are expected to be promising high-color purity light emitters that overcome inherent problems of conventional organic and inorganic quantum dot emitters. Within the last 2 y, perovskites have already demonstrated their great potential in light-emitting diodes by showing high electroluminescence efficiency comparable to those of organic and quantum dot light-emitting diodes. This article reviews the progress of perovskite emitters in two directions of bulk perovskite polycrystalline films and perovskite nanoparticles, describes current challenges, and suggests future research directions for researchers to encourage them to collaborate and to make a synergetic effect in this rapidly emerging multidisciplinary field. PMID- 27679845 TI - ERK5 kinase activity is dispensable for cellular immune response and proliferation. AB - Unlike other members of the MAPK family, ERK5 contains a large C-terminal domain with transcriptional activation capability in addition to an N-terminal canonical kinase domain. Genetic deletion of ERK5 is embryonic lethal, and tissue restricted deletions have profound effects on erythroid development, cardiac function, and neurogenesis. In addition, depletion of ERK5 is antiinflammatory and antitumorigenic. Small molecule inhibition of ERK5 has been shown to have promising activity in cell and animal models of inflammation and oncology. Here we report the synthesis and biological characterization of potent, selective ERK5 inhibitors. In contrast to both genetic depletion/deletion of ERK5 and inhibition with previously reported compounds, inhibition of the kinase with the most selective of the new inhibitors had no antiinflammatory or antiproliferative activity. The source of efficacy in previously reported ERK5 inhibitors is shown to be off-target activity on bromodomains, conserved protein modules involved in recognition of acetyl-lysine residues during transcriptional processes. It is likely that phenotypes reported from genetic deletion or depletion of ERK5 arise from removal of a noncatalytic function of ERK5. The newly reported inhibitors should be useful in determining which of the many reported phenotypes are due to kinase activity and delineate which can be pharmacologically targeted. PMID- 27679848 TI - Karl W. Butzer: Interdisciplinary mentor. PMID- 27679846 TI - Dissection of molecular assembly dynamics by tracking orientation and position of single molecules in live cells. AB - Regulation of order, such as orientation and conformation, drives the function of most molecular assemblies in living cells but remains difficult to measure accurately through space and time. We built an instantaneous fluorescence polarization microscope, which simultaneously images position and orientation of fluorophores in living cells with single-molecule sensitivity and a time resolution of 100 ms. We developed image acquisition and analysis methods to track single particles that interact with higher-order assemblies of molecules. We tracked the fluctuations in position and orientation of molecules from the level of an ensemble of fluorophores down to single fluorophores. We tested our system in vitro using fluorescently labeled DNA and F-actin, in which the ensemble orientation of polarized fluorescence is known. We then tracked the orientation of sparsely labeled F-actin network at the leading edge of migrating human keratinocytes, revealing the anisotropic distribution of actin filaments relative to the local retrograde flow of the F-actin network. Additionally, we analyzed the position and orientation of septin-GFP molecules incorporated in septin bundles in growing hyphae of a filamentous fungus. Our data indicate that septin-GFP molecules undergo positional fluctuations within ~350 nm of the binding site and angular fluctuations within ~30 degrees of the central orientation of the bundle. By reporting position and orientation of molecules while they form dynamic higher-order structures, our approach can provide insights into how micrometer-scale ordered assemblies emerge from nanoscale molecules in living cells. PMID- 27679847 TI - Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules. AB - Extracellular matrix (ECM) proteins are biosynthesized in the rough endoplasmic reticulum (rER) and transported via the Golgi apparatus to the extracellular space. The coat protein complex II (COPII) transport vesicles are approximately 60-90 nm in diameter. However, several ECM molecules are much larger, up to several hundreds of nanometers. Therefore, special COPII vesicles are required to coat and transport these molecules. Transmembrane Protein Transport and Golgi Organization 1 (TANGO1) facilitates loading of collagens into special vesicles. The Src homology 3 (SH3) domain of TANGO1 was proposed to recognize collagen molecules, but how the SH3 domain recognizes various types of collagen is not understood. Moreover, how are large noncollagenous ECM molecules transported from the rER to the Golgi? Here we identify heat shock protein (Hsp) 47 as a guide molecule directing collagens to special vesicles by interacting with the SH3 domain of TANGO1. We also consider whether the collagen secretory model applies to other large ECM molecules. PMID- 27679851 TI - Bilingual and Home Language Interventions With Young Dual Language Learners: A Research Synthesis. AB - Purpose: The purpose of this systematic review was to determine what bilingual or home language interventions have been found to be effective for 2- to 6-year-old dual language learners who have language impairment (LI) or are at risk for LI. Method: We conducted ancestral searches and searches of electronic databases, hand-searched article bibliographies, and searched 19 journals for experimental, quasiexperimental, or single-subject studies. Results: The review yielded 26 studies that were coded for quality, frequency and duration of the intervention, number of participants, location of intervention, interventionist, language(s) of intervention, and reported or calculated effect sizes. Studies were grouped by those that focused specifically on at-risk populations and those that focused on children with LI. Emerging trends provide support for bilingual and/or home language interventions for both children with LI and those at risk for LI. Conclusions: There were relatively few studies that met inclusion criteria, and the average quality rating for a study was 6.8 out of 9.0 possible points. More high-quality research is needed, particularly with populations that speak languages other than Spanish. Clinicians need more evidence-based recommendations to improve the language and literacy outcomes of the diverse range of dual language learners served in the United States and abroad. PMID- 27679852 TI - The Relationship of Novel Plasma Proteins in the Early Neonatal Period With Retinopathy of Prematurity. AB - Purpose: Retinopathy of prematurity (ROP) is a vision-threatening disease associated with abnormal retinal vascular development. Proteins from the insulin like growth factor pathway are related to ROP. However, there is a paucity of research on the role of other proteins in ROP. The aim of this study was to identify plasma proteins related to clinically significant ROP. Methods: We measured 1121 plasma proteins in the early neonatal period in infants at risk for ROP using an aptamer-based proteomic technology. The primary aim of the study was to compare plasma protein concentrations in infants who did (n = 12) and did not (n = 23) subsequently develop clinically significant ROP using logistic regression. As a secondary aim, we examined patterns in the proteins across categories of clinically significant, low-grade, and no ROP groups. Results: Lower levels of 16 proteins were associated with an increased risk of clinically significant ROP. In this group, superoxide dismutase (Mn), mitochondrial (MnSOD), and chordin-like protein 1 (CRDL1) were highly ranked. Other proteins in this group included: C-C motif chemokine 14 (HCC-1), prolactin, insulin-like growth factor-binding protein 7 (IGFBP-7), and eotaxin. Higher levels of 12 proteins were associated with a higher risk for ROP. Fibroblast growth factor 19 (FGF-19) was the top-ranked protein target followed by hepatocyte growth factor-like protein (MSP), luteinizing hormone (LH), cystatin M, plasminogen, and proprotein convertase subtilisin/kexin type 9 (PCSK9). We also noted different patterns in the trend of concentrations of proteins across the clinically significant, low grade, and no ROP groups. Conclusions: We discovered plasma proteins with novel associations with clinically significant ROP (MnSOD, CRDL1, PCSK9), proteins with links to established ROP signaling pathways (IGFBP-7), and proteins such as MnSOD that may be a target for future therapeutic interventions. PMID- 27679850 TI - Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis. AB - Copper homeostasis is essential for bacterial pathogen fitness and infection, and has been the focus of a number of recent studies. In Salmonella, envelope protection against copper overload and macrophage survival depends on CueP, a major copper-binding protein in the periplasm. This protein is also required to deliver the metal ion to the Cu/Zn superoxide dismutase SodCII. The Salmonella specific CueP-coding gene was originally identified as part of the Cue regulon under the transcriptional control of the cytoplasmic copper sensor CueR, but its expression differs from the rest of CueR-regulated genes. Here we show that cueP expression is controlled by the concerted action of CueR, which detects the presence of copper in the cytoplasm, and by CpxR/CpxA, which monitors envelope stress. Copper-activated CueR is necessary for the appropriate spatial arrangement of the -10 and -35 elements of the cueP promoter, and CpxR is essential to recruit the RNA polymerase. The integration of two ancestral sensory systems-CueR, which provides signal specificity, and CpxR/CpxA, which detects stress in the bacterial envelope-restricts the expression of this periplasmic copper resistance protein solely to cells encountering surplus copper that disturbs envelope homeostasis, emulating the role of the CusR/CusS regulatory system present in other enteric bacteria. PMID- 27679849 TI - Miro phosphorylation sites regulate Parkin recruitment and mitochondrial motility. AB - The PTEN-induced putative kinase 1 (PINK1)/Parkin pathway can tag damaged mitochondria and trigger their degradation by mitophagy. Before the onset of mitophagy, the pathway blocks mitochondrial motility by causing Miro degradation. PINK1 activates Parkin by phosphorylating both Parkin and ubiquitin. PINK1, however, has other mitochondrial substrates, including Miro (also called RhoT1 and -2), although the significance of those substrates is less clear. We show that mimicking PINK1 phosphorylation of Miro on S156 promoted the interaction of Parkin with Miro, stimulated Miro ubiquitination and degradation, recruited Parkin to the mitochondria, and via Parkin arrested axonal transport of mitochondria. Although Miro S156E promoted Parkin recruitment it was insufficient to trigger mitophagy in the absence of broader PINK1 action. In contrast, mimicking phosphorylation of Miro on T298/T299 inhibited PINK1-induced Miro ubiquitination, Parkin recruitment, and Parkin-dependent mitochondrial arrest. The effects of the T298E/T299E phosphomimetic were dominant over S156E substitution. We propose that the status of Miro phosphorylation influences the decision to undergo Parkin-dependent mitochondrial arrest, which, in the context of PINK1 action on other substrates, can restrict mitochondrial dynamics before mitophagy. PMID- 27679853 TI - Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation. AB - Purpose: We have previously demonstrated that soluble adenylyl cyclase (sAC) is necessary for retinal ganglion cell (RGC) survival and axon growth. Here, we further investigate the role of sAC in neuronal differentiation during retinal development. Methods: Chx10 or Math5 promoter-driven Cre-Lox recombination were used to conditionally delete sAC from early and intermediate retinal progenitor cells during retinal development. We examined cell type-specific markers expressed by retinal cells to estimate their relative numbers and characterize retinal laminar morphology by immunofluorescence in adult and newborn mice. Results: Retinal ganglion cell and amacrine cell markers were significantly lower in the retinas of adult Math5cre/sACfl/fl and Chx10cre/sACfl/fl mice than in those of wild-type controls. The effect on RGC development was detectable as early as postnatal day 1 and deleting sAC in either Math5- or Chx10-expressing retinal progenitor cells also reduced nerve fiber layer thickness into adulthood. The thickness of the photoreceptor layer was slightly but statistically significantly decreased in both the newborn Chx10cre/sACfl/fl and Math5cre/sACfl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sACfl/fl mice. Conclusions: sAC plays an important role in the early retinal development of RGCs as well as in the development of amacrine cells and to a lesser degree photoreceptors. PMID- 27679856 TI - The role of the mtDNA set point in differentiation, development and tumorigenesis. AB - Mitochondrial DNA replication is critical for maintaining mtDNA copy number to generate sufficient cellular energy that is required for development and for functional cells. In early development, mtDNA copy number is strictly regulated at different stages, and, as a result, the establishment of the mtDNA set point is required for sequential cell lineage commitment. The failure to establish the mtDNA set point results in incomplete differentiation or embryonic arrest. The regulation of mtDNA copy number during differentiation is closely associated with cellular gene expression, especially with the pluripotency network, and DNA methylation profiles. The findings from cancer research highlight the relationship between mitochondrial function, mtDNA copy number and DNA methylation in regulating differentiation. DNA methylation at exon 2 of DNA polymerase gamma subunit A (POLGA) has been shown to be a key factor, which can be modulated to change the mtDNA copy number and cell fate of differentiating and tumour cells. The present review combines multi-disciplinary data from mitochondria, development, epigenetics and tumorigenesis, which could provide novel insights for further research, especially for developmental disorders and cancers. PMID- 27679854 TI - The role of TREX in gene expression and disease. AB - TRanscription and EXport (TREX) is a conserved multisubunit complex essential for embryogenesis, organogenesis and cellular differentiation throughout life. By linking transcription, mRNA processing and export together, it exerts a physiologically vital role in the gene expression pathway. In addition, this complex prevents DNA damage and regulates the cell cycle by ensuring optimal gene expression. As the extent of TREX activity in viral infections, amyotrophic lateral sclerosis and cancer emerges, the need for a greater understanding of TREX function becomes evident. A complete elucidation of the composition, function and interactions of the complex will provide the framework for understanding the molecular basis for a variety of diseases. This review details the known composition of TREX, how it is regulated and its cellular functions with an emphasis on mammalian systems. PMID- 27679858 TI - TPL2 meets p38MAPK: emergence of a novel positive feedback loop in inflammation. AB - The activation of p38(MAPK) by Toll-like receptor signalling is essential for the inflammatory response of innate immunity due to its role in post-transcriptional regulation of TNFalpha and cytokine biosynthesis. p38(MAPK) activation proceeds by the upstream MAP2Ks, MAPK kinase (MKK)3/6 as well as MKK4, which in turn are substrates for MAP3Ks, such as TGFbeta-activated protein kinase-1 (TAK1). In contrast, TPL2 has been described as an exclusive MAP3K of MKK1/2-triggering activation of the classical ERKs, ERK1/2. In the recent issue of the Biochemical Journal, Pattison et al report their screening for TPL2 substrates in LPS stimulated macrophages and the identification of MKK3/6. Using catalytic-dead TPL2 (Map3k8(D270A/D270A)) knockin macrophages, they demonstrated that activation of MKK3/6 by TPL2 significantly contributes to LPS-dependent TNFalpha biosynthesis and is also essential for TNF-receptor 1 signalling. Hence, a new signalling pathway from TAK1 via IkappaB kinase, p105 NFkappaB and TPL2 to MKK3/6 and p38(MAPK) is established in macrophages. Taking into account that some isoforms of p38(MAPK) are necessary for maintaining functional steady-state levels of TPL2, a positive feedback loop in inflammation emerges. PMID- 27679855 TI - Targeting polyamine metabolism for cancer therapy and prevention. AB - The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention. PMID- 27679859 TI - Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood pressure independent effect. AB - Compound 21 (C21), selective agonist of angiotensin type-2 (AT-2) receptors, shows anti-inflammatory effects in experimental models of hypertension and nephroprotection in diabetes. The aim of the present study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague-Dawley rats. Cyclosporine-A (CsA; 15 mg/kg per day, intraperitoneal injection) and CsA plus C21 (0.3 mg/kg per day, intraperitoneal injection) were administered for 1 and 4 weeks. Control groups were left without any treatment. Blood pressure (plethysmographic method) and 24 h urinary albumin excretion were measured once a week. At the end of the experimental protocols, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and type IV collagen expression. After 1 and 4 weeks, the rats treated with CsA showed a significant increase (P<0.01) in blood pressure, no significant changes in urinary albumin excretion and a significant increase (P<0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared with the control rats. Treatment with C21 did not modify the CsA dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (P<0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared with rats treated with cyclosporine. The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases. PMID- 27679861 TI - Open eyes to sensory testing. PMID- 27679862 TI - Telephone review for people with epilepsy. AB - Telephone consultations are well suited to epilepsy review, particularly for those ineligible to drive. Careful patient selection and a courtesy call beforehand, by an administrator, increases efficiency and saves patient anxiety and clinician time. This paper gives advice based upon the author's experience of telephone review of patients with epilepsy. PMID- 27679860 TI - Association between genetic polymorphisms of interleukins and cerebral infarction risk: a meta-analysis. AB - Interleukins (ILs) are the most typical inflammatory and immunoregulatory cytokines. Evidences have shown that polymorphisms in ILs are associated with cerebral infarction risk. However, the results remain inconclusive. The present study was to evaluate the role of ILs polymorphisms in cerebral infarction susceptibility. Relevant case-control studies published between January 2000 and December 2015 were searched and retrieved from the electronic databases of Web of Science, PubMed, Embase and the Chinese Biomedical Database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. A total of 55 articles including 12619 cerebral infarction patients and 14436 controls were screened out. Four ILs (IL-1, IL-6, IL-10 and IL-18) contained nine single nucleotide polymorphisms (SNPs; IL-1alpha -899C/T, IL-1beta -511C/T and IL-1beta +3953C/T; IL-6 -174G/C and -572C/G; IL-10 -819C/T and 1082A/G; IL-18 -607C/A and -137G/C). Our result showed that IL-1alpha -899C/T and IL-18 -607C/A (under all the genetic models), and IL-6 -572C/G (under the allelic model, heterogeneity model and dominant model) were associated with increased the risk of cerebral infarction (P<0.05). Subgroup analysis by ethnicity showed that IL-6 -174G/C polymorphism (under all the five models) and IL-10 -1082A/G polymorphism (under the allelic model and heterologous model) were significantly associated with increased the cerebral infarction risk in Asians. Other genetic polymorphisms were not related with cerebral infarction susceptibility under any genetic models. In conclusion, IL-1alpha -899C/T, IL-6 -572C/G and IL-18 -607C/A might be risk factors for cerebral infarction development. Further studies with well-designed and large sample size are still required. PMID- 27679857 TI - Molecular signaling cascades involved in nonmelanoma skin carcinogenesis. AB - Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and the incidence continues to rise, in part due to increasing numbers in high-risk groups such as organ transplant recipients and those taking photosensitizing medications. The most significant risk factor for NMSC is ultraviolet radiation (UVR) from sunlight, specifically UVB, which is the leading cause of DNA damage, photoaging, and malignant transformation in the skin. Activation of apoptosis following UVR exposure allows the elimination of irreversibly damaged cells that may harbor oncogenic mutations. However, UVR also activates signaling cascades that promote the survival of these potentially cancerous cells, resulting in tumor initiation. Thus, the UVR-induced stress response in the skin is multifaceted and requires coordinated activation of numerous pathways controlling DNA damage repair, inflammation, and kinase-mediated signal transduction that lead to either cell survival or cell death. This review focuses on the central signaling mechanisms that respond to UVR and the subsequent cellular changes. Given the prevalence of NMSC and the resulting health care burden, many of these pathways provide promising targets for continued study aimed at both chemoprevention and chemotherapy. PMID- 27679863 TI - Sterile inflammation and pregnancy complications: a review. AB - Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1alpha and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins. PMID- 27679864 TI - A high-fat diet fed during different periods of life impairs steroidogenesis of rat Leydig cells. AB - This study evaluated the impact of a high-fat diet (HFD) during different stages of rat life, associated or not with maternal obesity, on the content of sex steroid hormones and morphophysiology of Leydig cells. The following periods of development were examined: gestation (O1), gestation and lactation (O2), from weaning to adulthood (O3), from lactation to adulthood (O4), gestation to adulthood (O5), and after sexual maturation (O6). The HFD contained 20% unsaturated fat, whereas the control diet had 4% fat. Maternal obesity was induced by feeding HFD 15 weeks before mating. All HFD groups presented increased body weight, hyperinsulinemia and reduced insulin sensitivity. Except for O1, all HFD groups exhibited a higher adiposity index, hyperleptinemia, reduced testosterone and estradiol testicular levels, and decreased testicular 17beta-HSD enzyme . Morphometrical analyses indicated atrophy of Leydig cells in the O2 group. Myelin vesicles were observed in the mitochondrial matrix of Leydig cells in O3, O4, O5 and O6, and autophagosomes containing mitochondria were found in O5 and O6. In conclusion, HFD feeding, before or after sexual maturation, reduces the functional capacity of rat Leydig cells. Maternal obesity associated with HFD during pregnancy/lactation prejudices Leydig cell steroidogenesis and induces its atrophy in adulthood, even if it is replaced by a conventional diet at later stages of life. Regardless of the life period of exposure to HFD, deregulation of leptin is the main factor related to steroidogenic impairment of Leydig cells, and, in groups exposed for longer periods (O3, O4, O5 and O6), this is worsened by structural damage and mitochondrial degeneration of these cells. PMID- 27679865 TI - Characterization of tetraspanin protein CD81 in mouse spermatozoa and bovine gametes. AB - Sperm-egg interaction and fusion represent a key moment of fertilization. In mammals, it is not possible without the interaction of the tetraspanin superfamily proteins including CD81. A detailed immunohistochemical localization of CD81 was monitored in bovine oocytes during different maturation stages, as well as during early embryogenesis. In addition, characterization of CD81 was carried out in bovine and mouse sperm. In bovine eggs, CD81 was detected on the plasma membrane of the germinal vesicle, metaphase I and metaphase II oocytes. During fertilization, accumulation of CD81 molecules in the perivitelline space of fertilized oocytes, which appeared as vesicles associated with plasma membrane, was observed. In majority of bull-ejaculated sperm and caput, corpus and cauda epididymal sperm, as well as mouse cauda epididymal sperm, CD81 was found on the plasma membrane covering the apical acrosome. Although the process of capacitation did not influence the localization of CD81, it was lost from the surface of the acrosome-reacted spermatozoa in bull, in contrast to mouse sperm where there was a relocalization of the CD81 protein during acrosome reaction across the equatorial segment and later over the whole sperm head. The presented results highlight conservative unifying aspects of CD81 expression between cattle and mouse, together with mouse-specific traits in sperm CD81 behaviour, which emphasizes certain species-specific mechanisms of fertilization to be considered. PMID- 27679866 TI - neo-Clerodane Diterpenoids and Other Constituents of Salvia filipes. AB - A series of neo-clerodane-type diterpenoids were isolated from the aerial parts of Salvia filipes, including the new compounds 4-epi-polystachyne A (1), salvifilines A (3), C (7), and D (8), and salvifiline B, which was isolated as the 15-O-methyl derivatives 4/5. In addition, the five known diterpenoids (2, 9 12), together with ursolic, oleanolic, and betulinic acids, and the flavone eupatorin were also isolated. The structures were determined by analysis of their spectroscopic data, mainly 1D and 2D NMR. The structure of salvifiline D was confirmed by X-ray analysis. The cytotoxic activities of the diterpenoids were evaluated, but all were inactive against a panel of six human cancer cell lines. PMID- 27679867 TI - Evaluation of the Swedish Web-Version of Quality of Recovery (SwQoR): Secondary Step in the Development of a Mobile Phone App to Measure Postoperative Recovery. AB - BACKGROUND: The majority of all surgeries are performed on an outpatient basis (day surgery). The Recovery Assessment by Phone Points (RAPP) app is an app for the Swedish Web-version of Quality of Recovery (SwQoR), developed to assess and follow-up on postoperative recovery after day surgery. OBJECTIVES: The objectives of this study are (1) to estimate the extent to which the paper and app versions of the SwQoR provide equivalent values; (2) to contribute evidence as to the feasibility and acceptability of a mobile phone Web-based app for measuring postoperative recovery after day surgery and enabling contact with a nurse; and (3) to contribute evidence as to the content validity of the SwQoR. METHODS: Equivalence between the paper and app versions of the SwQoR was measured using a randomized crossover design, in which participants used both the paper and app version. Feasibility and acceptability was evaluated by a questionnaire containing 16 questions regarding the value of the app for follow-up care after day surgery. Content validity evaluation was based on responses by day surgery patients and the staff of the day surgery department. RESULTS: A total of 69 participants completed the evaluation of equivalence between the paper and app versions of the SwQoR. The intraclass correlation coefficient (ICC) for the SwQoR was .89 (95% CI 0.83-0.93) and .13 to .90 for the items. Of the participants, 63 continued testing the app after discharge and completed the follow-up questionnaire. The median score was 69 (inter-quartile range, IQR 66-73), indicating a positive attitude toward using an app for follow-up after day surgery. A total of 18 patients and 12 staff members participated in the content validity evaluation. The item-level content validity index (I-CVI) for the staff group was in the 0.64 to 1.0 range, with a scale-level content validity index (S CVI) of 0.88. For the patient group, I-CVI was in the range 0.30 to 0.92 and S CVI was 0.67. The content validity evaluation of the SwQoR, together with three new items, led to a reduction from 34 to 24 items. CONCLUSIONS: Day surgery patients had positive attitudes toward using the app for follow-up after surgery, and stated a preference for using the app again if they were admitted for a future day surgery procedure. Equivalence between the app and paper version of the SwQoR was found, but at the item level, the ICC was less than .7 for 9 items. In the content validity evaluation of the SwQoR, staff found more items relevant than the patients, and no items found relevant by either staff or patients were excluded when revising the SwQoR. PMID- 27679868 TI - The co-occurrence of bronchial anthracofibrosis and interstitial lung disease. PMID- 27679869 TI - Prostate specific membrane antigen (PSMA) ligands for diagnosis and therapy of prostate cancer. AB - INTRODUCTION: Prostate specific membrane antigen (PSMA) has become an attractive diagnostic and therapeutic target for small molecule ligands. Radionuclide chelating ligands can be labeled with either 68Ga for positron-emission tomography (PET) or 177Lu for radionuclide therapy. Areas covered: In this literature review we evaluate the diagnostic value of 68Ga PSMA PET/CT and the therapeutic potential of 177Lu PSMA radioligand therapy (RLT) in patients with prostate cancer. 68Ga PSMA PET/CT is more accurate than CT for nodal staging and superior to conventional imaging in patients with biochemical recurrence, translating into major changes in clinical management. The preliminary data for 177Lu PSMA indicates >50% reduction of PSA levels in up to 59% of patients. Severe adverse events occurred <10% of patients after RLT. Expert commentary: PSMA ligands for diagnostic and therapeutic purpose will significantly impact the management of patients with prostate cancer. PMID- 27679870 TI - Assessment of forearm muscle spasticity with sonoelastography in patients with stroke. AB - OBJECTIVE: The aim of the study was to investigate the feasibility of sonoelastography to show muscle stiffness in post-stroke spasticity, and the relationship between sonoelastography findings and clinical spasticity scores in the spastic forearm muscles. METHODS: This study was carried out in a university rehabilitation centre. 23 patients with stroke with forearm muscle spasticity (>=1+ using the Modified Ashworth scale score and >=1 using the Tardieu scale) were included. Sonoelastography parameters (elasticity index and elasticity ratio) were measured from the flexor digitorum superficialis, flexor digitorum profundus, flexor carpi radialis and flexor carpi ulnaris muscles on the affected and unaffected sides. RESULTS: Both elasticity index and elasticity ratio of the wrist and finger flexors on the hemiplegic side were significantly increased compared with those on the healthy side (p < 0.05). The Tardieu angle of finger flexors was negatively correlated with the elasticity index and elasticity ratio measured in the spastic flexor digitorum profundus (r = -0.418 and r = -0.469, respectively). Tardieu angle of finger flexors was negatively correlated with the elasticity index measured in the spastic flexor digitorum superficialis (r = 0.435). There was no correlation between other parameters. CONCLUSION: Sonoelastography may provide objective assessment of spasticity both in diagnosis and follow-up. To strengthen this prediction, further studies are necessary. Advances in knowledge: The results of this study represent that sonoelastography is a promising evaluation method for forearm muscle spasticity. PMID- 27679871 TI - Factors influencing bacteraemia in patients with isomerism and CHD: the effects of functional splenic status and antibiotic prophylaxis. AB - BACKGROUND: "Heterotaxy syndrome", best segregated as isomerism, is characterised by laterality defects of the thoraco-abdominal organs, causing functional impairment. In particular, the spleen is frequently affected, increasing susceptibility to bacteraemia. This study explored factors that may increase the risk of bacteraemia in patients with isomerism. METHODS: We identified patients with CHD and isomerism. Review of outpatient, inpatient, and surgical records was conducted to collect data and determine trends in the cohort. A Cox regression analysis was conducted to determine factors influencing freedom from bacteraemia (Fig 1). RESULTS: We identified 83 patients with CHD and isomerism - 17 (20%) who had documented episodes of bacteraemia with a total of 21 episodes. A majority (86%) were nosocomial. The median age at the time of bacteraemia was 4 months. Although splenic anatomy did appear to influence the risk of bacteraemia in univariate analysis, this significance was lost with multivariate analysis. None of the other factors was significantly associated in either univariate or multivariate analysis. CONCLUSION: Specific factors such as splenic anatomy, atrial appendage isomerism, and antibiotic prophylaxis status are not significantly associated with the risk of bacteraemia in patients with CHD and isomerism. Nosocomial infections represent a majority of bacteraemia in these patients. PMID- 27679872 TI - Explore the Effects of Microstructural Defects on Voltage Fade of Li- and Mn-Rich Cathodes. AB - Li- and Mn-rich (LMR) cathode materials have been considered as promising candidates for energy storage applications due to high energy density. However, these materials suffer from a serious problem of voltage fade. Oxygen loss and the layered-to-spinel phase transition are two major contributors of such voltage fade. In this paper, using a combination of X-ray diffraction (XRD), pair distribution function (PDF), X-ray absorption (XAS) techniques, and aberration corrected scanning transmission electron microscopy (STEM), we studied the effects of micro structural defects, especially the grain boundaries, on the oxygen loss and layered-to-spinel phase transition through prelithiation of a model compound Li2Ru0.5Mn0.5O3. It is found that the nanosized micro structural defects, especially the large amount of grain boundaries created by the prelithiation can greatly accelerate the oxygen loss and voltage fade. Defects (such as nanosized grain boundaries) and oxygen release form a positive feedback loop, promote each other during cycling, and accelerate the two major voltage fade contributors: the transition metal reduction and layered-to-spinel phase transition. These results clearly demonstrate the important relationships among the oxygen loss, microstructural defects and voltage fade. The importance of maintaining good crystallinity and protecting the surface of LMR material are also suggested. PMID- 27679873 TI - Polycyclic Musks in the Air and Water of the Lower Great Lakes: Spatial Distribution and Volatilization from Surface Waters. AB - Polycyclic musks (PCMs) are synthetic fragrance compounds used in personal care products and household cleaners. Previous studies have indicated that PCMs are introduced to aquatic environments via wastewater and river discharge. Polyethylene passive samplers (PEs) were deployed in air and water during winter 2011 and summer 2012 to investigate the role of population centers as sources of these contaminants to the Great Lakes and determine whether the lakes were acting as sources of PCMs via volatilization. Average gaseous Sigma5PCM ranged from below detection limits (=5) score groups, respectively. The risk score C-statistics were 0.86 and 0.88 in the development and external validation samples, respectively (p < 0.001). Age >= 80 year was associated with the highest odds ratio (OR) of mortality (OR 8.07, 95% confidence interval (CI) 5.79-11.25). Other important predictors were acute cerebrovascular accident and acute respiratory failure. CONCLUSIONS: The risk of in-hospital mortality following TTS could be predicted using a simple risk score, which could aid in identifying and proper management of a higher risk group. PMID- 27679935 TI - Serum GDF-15 level in rheumatoid arthritis: relationship with disease activity and subclinical atherosclerosis. AB - OBJECTIVES: Growth differentiation factor (GDF)-15 was originally identified as a factor secreted by activated macrophages, and plays an important role in cell growth and differentiation. GDF-15 plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate the serum GDF-15 levels and their relationship with disease-related characteristics in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Forty-six patients diagnosed with RA and 36 demographically matched healthy control subjects participated in this study. GDF-15 levels were measured in blood samples from patients and controls. The disease activity score-28 (DAS28) was used to evaluate the disease activity of RA. The quality of life was evaluated using the disease-specific rheumatoid arthritis quality of life (RAQoL) scale. The health assessment questionnaire (HAQ) was used to evaluate the functional status. The degree of joint damage was assessed according to Larsen's method. Atherosclerosis was assessed by a cardiologist with the help of echocardiography according to the carotid intima media thickness (CIMT) method; vascular stiffness was assessed by using the flow mediated dilatation (FMD) method. RESULTS: Serum GDF-15 levels were significantly higher in RA patients when compared to the control subjects (p< 0.05). RA patients were divided into two groups according to the disease activity; while 26 subjects (57%) were in the active group, 20 patients were in the non-active group (43%). Serum GDF-15 levels were significantly higher in the group that was considered to have an active disease. According to Pearson's correlation, serum GDF-15 levels were positively correlated with erythrocyte sedimentation rate (ESR) levels, morning stiffness, DAS28 score, tender joint count, and CIMT (p<0.05). CONCLUSION: GDF-15 may play a role in the pathway of disease activity, joint involvement, and atherosclerosis in patients with rheumatoid arthritis. PMID- 27679936 TI - Quantum decoherence dynamics of divacancy spins in silicon carbide. AB - Long coherence times are key to the performance of quantum bits (qubits). Here, we experimentally and theoretically show that the Hahn-echo coherence time of electron spins associated with divacancy defects in 4H-SiC reaches 1.3 ms, one of the longest Hahn-echo coherence times of an electron spin in a naturally isotopic crystal. Using a first-principles microscopic quantum-bath model, we find that two factors determine the unusually robust coherence. First, in the presence of moderate magnetic fields (30 mT and above), the 29Si and 13C paramagnetic nuclear spin baths are decoupled. In addition, because SiC is a binary crystal, homo nuclear spin pairs are both diluted and forbidden from forming strongly coupled, nearest-neighbour spin pairs. Longer neighbour distances result in fewer nuclear spin flip-flops, a less fluctuating intra-crystalline magnetic environment, and thus a longer coherence time. Our results point to polyatomic crystals as promising hosts for coherent qubits in the solid state. PMID- 27679937 TI - The Role of Academic Institutions in Global Health: Building Partnerships With Low- and Middle-Income Countries. PMID- 27679938 TI - Significance of Extracellular Vesicles: Pathobiological Roles in Disease. AB - Over the past decade, many studies have been conducted on extracellular vesicles (EVs) in the fields of basic and clinical research. EVs are small sized membranous vesicles generated from many type of cells upon activation by environmental stresses such as heat, hypoxia, and irradiation. EVs theoretically consist of microparticles/microvesicles, exosomes, and apoptotic bodies by different productive mechanisms. Clinically, EVs are observed in the blood stream of patients suffering from acute and chronic inflammation evoked by various diseases, and number of EVs in blood flow is often dependent on the inflammatory status and severity of the diseases. To date, it has been reported that small molecules such as RNAs and proteins are encapsulated in EVs; however, the functions of EVs are still unclear in the biological, pathological, and clinical aspects. In this review, we summarize and discuss the biogenesis-based classification, expected function, and pathobiological activities of EVs. PMID- 27679940 TI - Liver transplantation in Brazil. PMID- 27679939 TI - Genome-wide identification of multifunctional laccase gene family in cotton (Gossypium spp.); expression and biochemical analysis during fiber development. AB - The single-celled cotton fibers, produced from seed coat epidermal cells are the largest natural source of textile fibers. The economic value of cotton fiber lies in its length and quality. The multifunctional laccase enzymes play important roles in cell elongation, lignification and pigmentation in plants and could play crucial role in cotton fiber quality. Genome-wide analysis of cultivated allotetraploid (G. hirsutum) and its progenitor diploid (G. arboreum and G. raimondii) cotton species identified 84, 44 and 46 laccase genes, respectively. Analysis of chromosomal location, phylogeny, conserved domain and physical properties showed highly conserved nature of laccases across three cotton species. Gene expression, enzymatic activity and biochemical analysis of developing cotton fibers was performed using G. arboreum species. Of the total 44, 40 laccases showed expression during different stages of fiber development. The higher enzymatic activity of laccases correlated with higher lignin content at 25 DPA (Days Post Anthesis). Further, analysis of cotton fiber phenolic compounds showed an overall decrease at 25 DPA indicating possible incorporation of these substrates into lignin polymer during secondary cell wall biosynthesis. Overall data indicate significant roles of laccases in cotton fiber development, and presents an excellent opportunity for manipulation of fiber development and quality. PMID- 27679941 TI - Assessment of antibiotic prophylaxis in surgical patients at the Gaffree e Guinle University Hospital. AB - OBJECTIVE: : to evaluate the antibiotic prophylaxis in surgical patients at the Gaffree e Guinle University Hospital - HUGG. METHODS: : we conducted a rospective study of a cohort of 256 patients undergoing elective operations between January and September 2014. We collected data on demographics, use or not of prophylactic antibiotic and the antibiotic prophylaxis following characteristics: type of antibiotic used, moment of administration and duration of postoperative use. The analyzed outcomes were "justified use or non-use of antibiotic prophylaxis", "correct antibiotic choice," "administration of the antibiotic at the right time" and "discontinuation of the antibiotic at the right time." RESULTS: : antibiotic prophylaxis was used in 91.8% of cases. The use or non-use of antibiotic prophylaxis was justified in 78.9% of patients, the choice of the administered antibiotic was considered correct in 97.9%, antibiotic administration was made at the right time in only 27.2% of patients and discontinuation of the antibiotic was performed at the correct time in 95.7% of cases. CONCLUSION: : the surgical antibiotic prophylaxis was not fully adequately performed in the sample. OBJETIVO: avaliar a antibioticoprofilaxia em pacientes cirurgicos do Hospital Universitario Gaffree e Guinle. METODOS: estudo prospectivo de uma coorte de 256 pacientes submetidos a operacoes eletivas, entre janeiro e setembro de 2014. Foram coletados dados demograficos dos pacientes, se ocorreu utilizacao ou nao do antibiotico profilatico e as seguintes caracteristicas da antibioticoprofilaxia: tipo de antibiotico utilizado, momento da administracao e tempo de duracao do uso no pos-operatorio. Os desfechos de interesse analisados foram "uso ou nao uso justificado da antibioticoprofilaxia", "escolha correta do antibiotico", "administracao do antibiotico no tempo correto" e "descontinuacao do antibiotico no tempo correto". RESULTADOS: a antibioticoprofilaxia foi utilizada em 91,8% dos casos. O uso ou nao uso da antibioticoprofilaxia foi justificado em 78,9% dos pacientes, a escolha do antibiotico administrado foi considerada correta em 97,9%, a administracao do antibiotico foi feita no momento correto em apenas 27,2% dos pacientes e a descontinuacao do antibiotico foi realizada no tempo correto em 95,7% dos casos. CONCLUSAO: a antibioticoprofilaxia cirurgica nao foi realizada de forma plenamente adequada na amostra estudada. PMID- 27679942 TI - Influence of duodenogastric reflux in the gastric mucosa histological changes of rats infected with Helicobacter pylori. AB - OBJECTIVE: to evaluate the influence of Duodenal reflux in histological changes of the gastric mucosa of rats infected with Helicobacter pylori submitted to pyloroplasty. METHODS: after two weeks of acclimation, we infected 30 male Wistar rats with Helicobacter pylori. We randomly divided them into three groups: one submitted to pyloroplasty, another to partial gastrectomy and the third, only infected, was not operated. After six months of surgery, euthanasia was carried out. Gastric fragments were studied by light microscopy to count the number of H. pylori, and to observe the histological changes (gastritis, metaplasia, dysplasia and neoplasia). We confirmed these changes by immunohistochemistry using the molecular markers PCNA and TGF-beta. RESULTS: the animals submitted to pyloroplasty had higher percentage of colonization by H. pylori (median=58.5; gastrectomy=16.5; control=14.5). There was a positive correlation between the amount of H. pylori and the occurrence of chronic gastritis present in the antral fragments. Neoplasia occurred in 40% of rats from the group submitted to pyloroplasty. The staining with PCNA and TGF-beta confirmed the histopathological changes visualized by optical microscopy. CONCLUSIONS: the antral region was the one with the highest concentration of H. pylori, regardless of the group. There was a positive correlation between the appearance of benign disorders (chronic gastritis, metaplasia, dysplasia) and cancer in mice infected with H. pylori submitted to pyloroplasty. OBJETIVO: avaliar a influencia do refluxo duodenogastrico nas alteracoes histologicas da mucosa gastrica de ratos, infectados por Helicobacter pylori, submetidos a piloroplastia. METODO: apos duas semanas de aclimatacao, 30 ratos machos da raca Wistar, foram infectados com o microorganismo patogenico H. pylori. De forma aleatoria, foram divididos em tres grupos: um submetido a piloroplastia, outro a gastrectomia parcial e o terceiro, apenas infectados, nao foi operado. Apos seis meses de operados, procedeu-se a eutanasia. Os fragmentos gastricos foram estudados por microscopia optica, para a contagem da quantidade de H. pylori, e para a observacao das alteracoes histologicas (gastrite, metaplasia, displasia e neoplasia). A confirmacao dessas alteracoes foi feita por imuno-histoquimica, utilizando os marcadores moleculares PCNA e TGFbeta. RESULTADOS: os animais submetidos a piloroplastia tiveram maior percentual de colonizacao por H. pylori (mediana=58,5; gastrectomia=16,5; controle=14,5). Houve correlacao positiva entre quantidade de H. pylori e ocorrencia de gastrite cronica presente nos fragmentos do antro. Ocorreu 40% de neoplasia no grupo submetido a piloroplastia. A marcacao de PCNA e TGF-beta confirmou as alteracoes histopatologicas visibilizadas a microscopia optica. CONCLUSOES: a regiao do antro foi a que apresentou a maior concentracao de H. pylori, independente do grupo. Houve correlacao positiva entre e o aparecimento de alteracoes benignas (gastrite cronica, metaplasia, displasia), e de neoplasia nos ratos infectados com H. pylori submetidos a piloroplastia. PMID- 27679943 TI - Mirizzi syndrome grades III and IV: surgical treatment. AB - OBJECTIVE: : to evaluate the epidemiology and outcomes of surgical treatment of patients with Mirizzi Syndrome (MS) grades III and IV, the most advanced according to Csendes classification. METHODS: : we conducted a retrospective, cross-sectional study by reviewing records of thirteen patients with grades III and IV MS operated from December 2001 to September 2013, among the 3,691 cholecystectomies performed in the period. RESULTS: : the incidence of MS was 0.6% (23 cases) and grades III and IV amounted to 0.35% of this number. There was a predominance of type IV (12 cases). The preoperative diagnosis was possible in 53.8% of cases. The preferred approach was biliary-digestive derivation (10 cases), and "T" tube drainage with suture of the bile duct was the choice in three special occasions. Three patients had biliary fistula resolved with clinical management, and one coliperitoneum case required reoperation. In the outpatient follow-up of patients who underwent biliodigestive anastomosis (eight), 50% are asymptomatic, 25% had anastomotic stricture and 25% lost follow up. The mean follow-up was 41.8 months. CONCLUSION: : MS in advanced degrees has low incidence, preoperative diagnosis in only half of cases, and has the biliodigestive anastomosis as the best conduct, but not without morbidity. OBJETIVO: avaliar a epidemiologia e os resultados do tratamento cirurgico de doentes portadores de graus III e IV, mais avancados, da Sindrome de Mirizzi (SM) de acordo com a classificacao de Csendes. METODOS: estudo retrospectivo, de corte transversal atraves da revisao de prontuarios de 13 pacientes portadores de graus III e IV da SM operados de dezembro de 2001 a setembro de 2013, entre 3691 colecistectomias realizadas neste periodo. RESULTADOS: a incidencia da SM foi 0,6% (23 casos) e os graus III e IV perfizeram 0,35% deste numero. Houve um predominio de tipo IV (12 casos). O diagnostico pre-operatorio foi possivel em 53,8% dos casos. A conduta preferencial foi derivacao biliodigestiva (10 casos) e foi optado por drenagem com tubo "T" e sutura da via biliar em tres ocasioes especiais. Tres pacientes apresentaram fistula biliar resolvida com conduta expectante e um caso de coleperitonio necessitou reoperacao. No seguimento ambulatorial dos pacientes que realizaram a anastomose biliodigestiva (oito), 50% estao assintomaticos, 25% apresentaram estenose da anastomose e 25% perderam seguimento. O tempo medio de acompanhamento foi 41,8 meses. CONCLUSAO: de incidencia baixa e de diagnostico pre-operatorio em apenas metade dos casos, a SM em graus avancados tem na anastomose biliodigestiva sua melhor conduta, porem nao isenta de morbimortalidade. PMID- 27679944 TI - Clinical-epidemiological profile of acute appendicitis: retrospective analysis of 638 cases. AB - OBJECTIVE: to describe the clinical and epidemiological profile of acute appendicitis (AA) of the patients treated at a referral center in the Juiz de Fora macro-region, Minas Gerais State, Brazil. METHODS: we conducted a retrospective, observational study in the Dr. Mozart Geraldo TeixeiraEmergency Hospital. We selected 638 patients diagnosed with AA, and analyzed the variables gender, age, evolutionary phase, length of hospital stay, pathological diagnosis, use of antibiotics, use of drains, complications and mortality. RESULTS: AA was more prevalent in young adults (19-44 years) and males (65.20%). The mean hospital stay was seven days and phase II was the most prevalent. We found the histopathological diagnosis of primary tumor of the appendix in six patients (0.94%), adenocarcinoma being the most common histologic type (66.7%). Regarding the use of antibiotics, 196 patients underwent antibiotic prophylaxis and 306 received antibiotic therapy. Eighty-one patients used some kind of drain, for an average of 4.8 days. Seventeen patients died (2.67%), predominantly males (70.59%), with mean age of 38.47 years. CONCLUSION: AA has a higher prevalence in males and young adults. The length of stay is directly associated with the evolutionary phase. The most common complication is infection of the surgical site. Mortality in our service is still high when compared with developed centers. OBJETIVO: avaliar a epidemiologia e os resultados do tratamento cirurgico de doentes portadores de graus III e IV, mais avancados, da Sindrome de Mirizzi (SM) de acordo com a classificacao de Csendes. METODOS: estudo retrospectivo, de corte transversal atraves da revisao de prontuarios de 13 pacientes portadores de graus III e IV da SM operados de dezembro de 2001 a setembro de 2013, entre 3691 colecistectomias realizadas neste periodo. RESULTADOS: a incidencia da SM foi 0,6% (23 casos) e os graus III e IV perfizeram 0,35% deste numero. Houve um predominio de tipo IV (12 casos). O diagnostico pre operatorio foi possivel em 53,8% dos casos. A conduta preferencial foi derivacao biliodigestiva (10 casos) e foi optado por drenagem com tubo "T" e sutura da via biliar em tres ocasioes especiais. Tres pacientes apresentaram fistula biliar resolvida com conduta expectante e um caso de coleperitonio necessitou reoperacao. No seguimento ambulatorial dos pacientes que realizaram a anastomose biliodigestiva (oito), 50% estao assintomaticos, 25% apresentaram estenose da anastomose e 25% perderam seguimento. O tempo medio de acompanhamento foi 41,8 meses. CONCLUSAO: de incidencia baixa e de diagnostico pre-operatorio em apenas metade dos casos, a SM em graus avancados tem na anastomose biliodigestiva sua melhor conduta, porem nao isenta de morbimortalidade. PMID- 27679945 TI - Collagen, fibrinogen and thrombin biological addesive is effective in treating experimental liver injuries. AB - OBJECTIVE: : to evaluate the effectiveness of a collagen-based adhesive associated with fibrinogen and thrombin in experimental liver injury in rats. METHODS: : the study included 30 Wistar rats randomly divided into three groups: A, B and C. All underwent standard liver traumatic injury. In group A the lesion was treated with the adhesive; in group B, with conventional absorbable suture; and in group C, there was no treatment. We analyzed the time of hemostasis, mortality, occurrence of adhesions and any histological changes. RESULTS: : there was no statistical difference in relation to mortality (p = 0.5820). The group treated with the adhesive showed the lowest hemostasis times (p = 0.0573, odds ratio 13.5) and lower incidence of adhesions (p = 0.0119). Microscopic histological alterations of Groups A and B were similar, with foreign body granuloma formation separating the adhesive material or the suture from the hepatic stroma. CONCLUSION: : the adhesive of collagen associated with fibrinogen and thrombin was effective in the treatment of experimental hepatic injury, providing a lower incidence of adhesions between the liver and surrounding structures. OBJETIVO: avaliar a eficacia de um adesivo a base de colageno associado a fibrinogenio e trombina, no trauma hepatico experimental em ratos. METODOS: foram incluidos no estudo 30 ratos Wistar, igualmente divididos aleatoriamente em tres grupos: A, B e C. Todos foram submetidos a lesao traumatica hepatica padronizada. No grupo A a lesao foi tratada com o adesivo, no grupo B com sutura convencional com fio absorvivel e no grupo C nao houve tratamento da lesao. Foram analisados o tempo de hemostasia, mortalidade, ocorrencia de aderencias e eventuais alteracoes histologicas. RESULTADOS: os resultados mostraram que nao houve diferenca estatistica em relacao a mortalidade (p=0,5820). O grupo tratado com adesivo apresentou os menores tempos de hemostasia (p=0,0573 e odds ratio 13,5) e menor ocorrencia de aderencias (p=0,0119). Microscopicamente, as alteracoes histologicas dos grupos A e B foram semelhantes, com a formacao de granuloma de corpo estranho separando o material do adesivo e do fio de sutura do estroma hepatico. CONCLUSAO: o estudo concluiu que o adesivo de colageno associado a fibrinogenio e trombina foi eficaz no tratamento do trauma hepatico experimental, proporcionado menor ocorrencia de aderencias entre o figado e as estruturas vizinhas. PMID- 27679946 TI - Diagnosis of aggressive subtypes of eyelid basal cell carcinoma by 2-mm punch biopsy: prospective and comparative study. AB - OBJECTIVE: : to compare the accuracy of preoperative 2-mm punch biopsy at one site and at two sites in the diagnosis of aggressive subtypes of eyelid basal cell carcinoma (BCC). METHODS: : we randomly assigned patients to Group 1 (biopsy at one site) and Group 2 (biopsy at two sites). We compared the biopsy results to the gold standard (pathology of the surgical specimen). We calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Kappa coefficient to determine the level of agreement in both groups. RESULTS: : we analyzed 105 lesions (Group 1: n = 44; Group 2: n = 61). The agreement was 54.5% in Group 1 and 73.8% in Group 2 (p = 0.041). There was no significant difference between the groups regarding the distribution of quantitative and qualitative variables (gender, age, disease duration, tumor larger diameter, area and commitment of margins). Biopsy at two sites was two times more likely to agree with the gold standard than the biopsy of a single site. CONCLUSIONS: : the accuracy and the performance indicators were better for 2-mm punch biopsy in two sites than in one site for the diagnosis of aggressive subtypes of eyelid BCC. OBJETIVO: comparar a acuracia da biopsia pre-operatoria por trepano de 2mm em um sitio e em dois sitios no diagnostico dos subtipos agressivos de carcinoma basocelular (CBC) palpebral. METODOS: os pacientes foram distribuidos aleatoriamente em Grupo 1 (biopsia em um sitio) e Grupo 2 (biopsia em dois sitios). Os resultados das biopsias foram comparados com o padrao-ouro (exame anatomopatologico da peca cirurgica). A sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo, precisao e coeficiente Kappa foram calculados para determinar o nivel de concordancia nos dois grupos. RESULTADOS: foram analisadas 105 lesoes (Grupo 1: n = 44; Grupo 2: n = 61). A concordancia foi de 54,5% no Grupo 1 e 73,8% no Grupo 2 (p-valor = 0,041). Nao houve diferenca significativa entre os grupos quanto a distribuicao das variaveis quantitativas e qualitativas (sexo, idade, duracao da doenca, maior diametro do tumor, area e comprometimento de margens). A biopsia em dois sitios mostrou duas vezes mais chance de concordar com o padrao-ouro do que a biopsia de um sitio. CONCLUSOES: a acuracia e os indicadores de desempenho foram melhores para a biopsia por trepano de 2 mm em dois sitios do que em um sitio para o diagnostico dos subtipos agressivos de CBC palpebral. PMID- 27679947 TI - Single transverse extended incision for radical neck dissection. AB - OBJECTIVE: to assess the efficacy of the single transverse extended cervical incision in radical neck dissection. METHOD: we conducted a prospective study, from January 2008 to January 2009, with 18 patients undergoing surgical treatment of malignant tumors of the upper aero-digestive tract. The primary lesion was located in the oral cavity in eight cases, in the oropharynx in three, in the hypopharynx in three, in the larynx in two, in the maxillary sinus, and in one case, the primary injury was hidden. There were 29 neck dissections, eight bilateral and 10 unilateral (26 radical and three selective). Staging revealed nine patients with T4 tumor, one T3, six T2, one T1 and one Tx. Five patients were N0, nine N2b, one N2c and three N3. The average number of dissected lymph nodes was 34.25. We performed the neck dissection through a single incision located in the middle neck, coincident with the skinfold, with a length of about 2 to 3 cm behind the anterior edge of the trapezius muscle and 3 to 4 cm from the midline for the unilateral neck dissections. RESULTS: as complications, there were myocutaneous flap necrosis in one patient with prior radiation therapy, one lymphatic fistula, one dehiscence of the tracheostomy, one cervical abscess, one salivary fistula and one suture dehiscence. CONCLUSIONS: the single extended incision provides adequate exposure of the neck structures, without compromising surgical time, even in bilateral dissections. It does not compromise the resection of all cervical lymph nodes; it has excellent aesthetic and functional results and is easily associated with other approaches to resection of the primary tumor. OBJETIVO: verificar a eficacia da incisao cervical unica, transversa e estendida, para o esvaziamento cervical radical. METODO: estudo prospectivo, de janeiro de 2008 a janeiro de 2009, de 18 pacientes submetidos a tratamento cirurgico de tumores malignos da via aero-digestiva superior. A lesao primaria se situava na cavidade oral em oito casos, na orofaringe em tres, no seio piriforme em tres, na laringe em dois, no seio maxilar em um e em um caso a lesao primaria era oculta. Houve 29 esvaziamentos, sendo oito bilaterais e 10 unilaterais (26 radicais e tres seletivos). O estadiamento revelou nove pacientes com tumor T4, um T3, seis T2, um T1 e um Tx. Cinco pacientes eram N0, nove N2b, um N2c e tres N3. A media de linfonodos dissecados foi de 34,25. O esvaziamento cervical foi realizado por meio de uma unica incisao localizada no terco medio do pescoco, coincidente com dobra cutanea, com extensao de cerca de 2 a 3 cm para tras da borda anterior do musculo trapezio e 3 a 4 cm da linha media para os esvaziamentos cervicais unilaterais. RESULTADOS: como complicacoes houve necrose de retalho miocutaneo em um paciente com radioterapia previa, uma fistula linfatica, uma deiscencia do traqueostoma, um abscesso cervical, uma fistula salivar e uma deiscencia de sutura. CONCLUSOES: a incisao unica e estendida proporciona exposicao adequada das estruturas do pescoco, sem comprometer o tempo cirurgico, mesmo em esvaziamentos bilaterais. Nao compromete a resseccao de todos os linfonodos cervicais, apresenta excelentes resultados esteticos e funcionais e e facilmente associada com outras abordagens para resseccao do tumor primario. PMID- 27679949 TI - Gastric wall changes after intragastric balloon placement: a preliminary experience. AB - OBJECTIVE: : to evaluate the thickness of the gastric wall at the time of intra gastric balloon (IGB) placement, at the time of its withdrawal and one month after withdrawal. METHODS: : fifteen morbidly obese patients underwent the introduction of IGB under general anesthesia. In all patients, there was infusion of 500ml of distilled water in the balloon for the test. Measurements of the thickness of the gastric wall were made in the antrum, body and proximal body, using a radial echoendoscope with a frequency of 12MHz and maximum zoom, and its own balloon inflated with 5ml of distilled water. RESULTS: : the presence of IGB led to increased wall thickness of the gastric body by expanding the muscle layer. These changes were apparently transient, since 30 days after the balloon withdrawal there was a tendency to return of the wall thickness values observed before the balloon insertion. CONCLUSION: : the use of intragastric balloon for the treatment of obesity determines transient increase in the wall thickness of the gastric body caused by expanded muscle layer. OBJETIVO: avaliar a espessura da parede gastrica no momento do posicionamento do balao intragastrico (BIG), no momento de sua retirada e um mes apos a retirada. METODOS: quinze pacientes obesos morbidos foram submetidos a introducao de BIG sob anestesia geral. Em todos os pacientes foi feita infusao de 500 ml de agua destilada e o balao foi insuflado com 5ml de agua destilada. As medidas da espessura da parede gastrica foram feitas no antro, corpo e corpo alto utilizando-se um ecoendoscopio radial com frequencia de 12MHz e zoom maximo. RESULTADOS: a presenca do BIG levou ao aumento da espessura da parede do corpo gastrico pelo aumento de espessura da sua camada muscular. Estas alteracoes sao aparentemente transitorias ja que apos 30 dias da retirada do balao existiu uma tendencia de retorno da espessura da parede aos valores observados antes do seu posicionamento. CONCLUSAO: a utilizacao do balao intragastrico para tratamento da obesidade determina aumento transitorio da espessura da parede do corpo gastrico causado pelo aumento da camada muscular. PMID- 27679948 TI - Age-related changes in bone architecture. AB - OBJECTIVE: : to evaluate the histologic and morphometric characteristics of bone biopsies of the anterior iliac crest of patients of different age groups. METHODS: : we studied 30 bone samples from the iliac crest, using brightfield optical microscopy. We divided the samples by donors' age groups in three groups: Group 1 (n = 10), subjects aged between 25 and 39 years; Group 2 (n = 10), subjects aged between 40 and 64 years; Group 3 (n = 10), individuals aged 65 years and over. We randomly divided the samples into two sets with 15 specimens. In the first study segment (n = 15), we used histological to assess the osteogenic property of the graft, through the analysis of cell reserve in the periosteum, the number of osteocytes in the lacunae and the number of Haversian and Volkmann's canals. In the second study segment (n = 15), we investigated the morphology of osteoconductive property of the graft, through quantification of the trabecular meshwork (Vv) and trabecular area (Sv). RESULTS: : histologically, we observed degeneration of bone occurring with age, characterized by thinning of the periosteum, with gradual replacement of the steogenic layer by fibrous tissue, small amount of Haversian and Volkmann's canals, osteocyte lacunae voids and fine spongy bone trabeculae, allowing ample medullary space, usually occupied by fat cells and adipocytes. Morphologically, with respect to the quantification of the trabecular meshwork (Vv), we found statistically significant differences between Groups 1 and 3 and between Groups 2 and 3, with reduction of the trabecular meshwork of about 45% in the elderly over 65 years old ; there was no statistically significant difference between Groups 1 and 2. There was also no statistical difference between the Groups regarding Sv. CONCLUSION: : the results of this experiment suggest that, in the elderly (over 65 years old), the osteogenic property of autologous bone graft decreases and the osteoconductive property is compromised. OBJETIVO: avaliar as caracteristicas histologicas e morfometricas de biopsias osseas da regiao anterior da crista iliaca de pacientes de diferentes faixas etarias. METODOS: foram estudadas 30 amostras de osso da crista iliaca, utilizando-se microscopia optica de campo claro. As amostras foram divididas pela faixa etaria dos doadores em tres grupos: Grupo 1 (n = 10), individuos com idade entre 25 e 39 anos; Grupo 2 (n = 10), individuos com idade entre 40 e 64 anos; Grupo 3 (n = 10), individuos com idade igual ou superior a 65 anos. As amostras foram separadas aleatoriamente em dois conjuntos com 15 pecas. No primeiro segmento do estudo (n = 15), foi avaliada histologicamente a propriedade osteogenica do enxerto, atraves da analise da reserva celular no periosteo, do numero de osteocitos nas lacunas e da quantidade de canais de Havers e de Volkmann. No segundo segmento do estudo (n = 15), investigou-se morfologicamente a propriedade osteocondutora do enxerto, atraves da quantificacao da rede trabecular (Vv) e da area trabecular (Sv). RESULTADOS: histologicamente, observou-se que ocorre degeneracao do tecido osseo com a idade, caracterizada pelo adelgacamento do periosteo, com substituicao gradual da camada osteogenica por tecido fibroso, pequena quantidade de canais de Havers e de Volkmann, osteoplastos vazios e trabeculas finas de osso esponjoso, permitindo amplo espaco medular, em geral ocupado por celulas lipidicas e adipocitos. Morfologicamente, com relacao a quantificacao da rede trabecular (Vv), foi observada diferenca estatisticamente significante entre os Grupos 1 e 3 e entre os Grupos 2 e 3, com reducao da rede trabecular de cerca de 45% no idoso acima de 65 anos de idade; nao foi observada diferenca estatisticamente significante entre os Grupos 1 e 2. Nao foi observada diferenca estatistica entre os grupos quanto a Sv. CONCLUSAO: os achados do presente experimento sugerem que nos individuos idosos (acima de 65 anos de idade), a propriedade osteogenica do enxerto osseo autologo diminui e a propriedade osteocondutora esta comprometida. PMID- 27679950 TI - Robotic-assisted modified retroauricular cervical approach: initial experience in Latin America. AB - OBJECTIVE: to evaluate the thickness of the gastric wall at the time of intra gastric balloon (IGB) placement, at the time of its withdrawal and one month after withdrawal. METHODS: fifteen morbidly obese patients underwent the introduction of IGB under general anesthesia. In all patients, there was infusion of 500ml of distilled water in the balloon for the test. Measurements of the thickness of the gastric wall were made in the antrum, body and proximal body, using a radial echoendoscope with a frequency of 12MHz and maximum zoom, and its own balloon inflated with 5ml of distilled water. RESULTS: the presence of IGB led to increased wall thickness of the gastric body by expanding the muscle layer. These changes were apparently transient, since 30 days after the balloon withdrawal there was a tendency to return of the wall thickness values observed before the balloon insertion. CONCLUSION: the use of intragastric balloon for the treatment of obesity determines transient increase in the wall thickness of the gastric body caused by expanded muscle layer. RESUMO: A preocupacao com a melhoria dos resultados esteticos e funcionais sem comprometimento dos resultados oncologicos na cirurgia de cabeca e pescoco tem aumentado significativamente. Os procedimentos minimamente invasivos e principalmente aqueles que utilizam a tecnologia robotica permitiram o desenvolvimento de novas abordagens, incluindo o acesso retroauricular, que agora e usado rotineiramente, especialmente na Coreia do Sul. A presente nota ira ilustrar a tecnica e a experiencia inicial na America Latina, demonstrando que esta abordagem e viavel, segura e eficaz oncologicamente, podendo ser utilizada em casos selecionados com um beneficio estetico evidente. PMID- 27679951 TI - Bronchial fistula closure with negative pressure wound therapy: a feasible and cost-effective treatment. AB - Treatment of bronchial fistula (BF) after pulmonary lobectomy is a challenge. Often, patients require long hospital stay, have recurrent empyema and pneumonia, are susceptible to sepsis, often need broad-spectrum antibiotics, as well as various surgical approaches. With the advent and growing evidence of the benefits of negative pressure therapy (NPT), its use in some patients with BF has been reported with encouraging results concerning its feasibility and cost effectiveness. The aim of this study was to demonstrate the application of NPT as a resource for BF treatment and comparatively analyze the overall cost of treatment. RESUMO O tratamento de fistula bronquica (FB) apos lobectomia pulmonar e um desafio. Muitas vezes, o paciente demanda longo tempo de internacao, apresenta recidivas de empiema e pneumonia, pode evoluir para sepse, frequentemente necessita de antibioticoterapia de amplo espectro, bem como de varias abordagens cirurgicas. Com o advento e acumulo de evidencias dos beneficios da terapia por pressao negativa (TPN), seu uso em alguns pacientes com FB tem sido relatado com resultados animadores relativos a sua viabilidade e ao seu custo-efetividade. O objetivo deste estudo foi demonstrar a aplicacao de TPN como recurso para tratamento da FB e analisar comparativamente o custo global do seu tratamento. PMID- 27679952 TI - Profile of the newly graduated physicians in southern Brazil and their professional insertion. AB - Knowledge of the profile and professional integration of new graduates enables adjustments in medical education. This study evaluated 107 graduates from a private institution in the Brazilian South region, using a self-administered electronic questionnaire. There were similar participation of young physicians of both genders and higher male concentration in general surgery. Graduates are inserted in the public and private labor market. Most do extra shifts in emergency services and trauma surgery, where there is greater need for clinical and surgical skills. These findings suggest that adequate surgical training during graduation is critical to employability. RESUMO O conhecimento do perfil e insercao profissional dos recem-formados possibilita ajustes na educacao medica. Este estudo avaliou 107 egressos de instituicao privada no sul do pais, utilizando questionario eletronico autoaplicavel. Houve participacao similar de jovens de ambos os sexos e maior concentracao masculina na area de cirurgia geral. Os egressos estao inseridos no mercado de trabalho publico e privado. A maioria faz plantoes extras em servicos de emergencia e cirurgia do trauma, onde ha maior necessidade de habilidades clinicas e cirurgica. Esses achados apontam que a formacao cirurgica adequada durante a graduacao e fundamental para a empregabilidade. PMID- 27679953 TI - Cesarean section by maternal request. AB - Cesarean section by maternal request is the one performed on a pregnant woman without medical indication and without contraindication to vaginal delivery. There is great controversy over requested cesarean section. Potential risks include complications in subsequent pregnancies, such as uterine rupture, placenta previa and accreta. Potential benefits of requested cesareans include a lower risk of postpartum hemorrhage in the first cesarean and fewer surgical complications compared with vaginal delivery. Cesarean section by request should never be performed before 39 weeks. RESUMO A cesariana a pedido materno e aquela realizada em uma gestante sem indicacoes medicas e sem contraindicacao para tentativa do parto vaginal. Existe grande controversia sobre a realizacao da cesariana a pedido. Riscos potenciais da cesariana a pedido incluem complicacoes em gravidezes subsequentes, tais como: rotura uterina, placenta previa e acretismo. Potenciais beneficios da cesariana a pedido englobam um menor risco de hemorragia pos-parto na primeira cesariana e menos complicacoes cirurgicas quando comparada ao parto vaginal. A cesariana a pedido jamais deve ser realizada antes de 39 semanas. PMID- 27679955 TI - Prioritising minimum standards of emergency care for children in resource-limited settings. AB - BACKGROUND: There is global variation in the ability of hospital-based emergency centres to provide paediatric emergency medicine (PEM) services. Although minimum standards have been proposed, they may not be applicable in resource-limited settings. OBJECTIVE: The goal was to identify reasonable minimum standards to provide safe and effective care for acutely ill children in resource-limited settings. METHODS: Using previously proposed standards from the International Federation of Emergency Medicine (IFEM), a modified Delphi approach was used to reach agreement regarding minimum standards for PEM in resource-limited settings. Three rounds of surveys were electronically distributed to physicians working in resource-limited settings. Those standards with >67% agreement advanced to the subsequent round. RESULTS: The categories of the surviving criteria included integrated service design, child and family-friendly care, initial assessment of the ill child, stabilising and treating an ill child, staff training and competence, equipment, supplies and medications, quality and safety, child protection, and advanced training and academic research. CONCLUSIONS: Experts with experience in acute care of children in resource-limited settings have prioritised standards for paediatric emergency care. They identified 26 variables in nine domains from the original IFEM list of standards and two additional free text standards for the care of acutely ill children. This list may serve as a helpful guide for emergency centres to provide medical treatment for acutely ill children in resource-limited settings. PMID- 27679954 TI - IFN-gamma Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells. AB - Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of 6-day-old mice induces mucous metaplasia and airways hyperresponsiveness, which is dependent on IL-13, IL-25, and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-gamma expression, in contrast to mature 8-week-old mice with a robust IFN-gamma response, consistent with the notion that deficient IFN-gamma production in immature mice permits RV-induced type 2 immune responses. We therefore examined the effects of intranasal IFN gamma administration on RV-induced ILC2 expansion and IL-13 expression in 6-day old BALB/c and IL-13 reporter mice. Airway responses were assessed by histology, immunofluorescence microscopy, quantitative polymerase chain reaction, ELISA, and flow cytometry. Lung ILC2s were also treated with IFN-gamma ex vivo. We found that, compared with untreated RV-infected immature mice, IFN-gamma treatment attenuated RV-induced IL-13 and Muc5ac mRNA expression and mucous metaplasia. IFN gamma also reduced ILC2 expansion and the percentage of IL-13-secreting ILC2s. IFN-gamma had no effect on the mRNA or protein expression of IL-25, IL-33, or thymic stromal lymphoprotein. Finally, IFN-gamma treatment of sorted ILC2s reduced IL-5, IL-13, IL-17RB, ST2, and GATA-3 mRNA expression. We conclude that, in immature mice, IFN-gamma inhibits ILC2 expansion and IL-13 expression in vivo and ex vivo, thereby attenuating RV-induced mucous metaplasia. These findings demonstrate the antagonistic function of IFN-gamma on ILC2 expansion and gene expression, the absence of which may contribute to the development of an asthma like phenotype after early-life RV infection. PMID- 27679956 TI - Thresholds in marsh resilience to the Deepwater Horizon oil spill. AB - Ecosystem boundary retreat due to human-induced pressure is a generally observed phenomenon. However, studies that document thresholds beyond which internal resistance mechanisms are overwhelmed are uncommon. Following the Deepwater Horizon (DWH) oil spill, field studies from a few sites suggested that oiling of salt marshes could lead to a biogeomorphic feedback where plant death resulted in increased marsh erosion. We tested for spatial generality of and thresholds in this effect across 103 salt marsh sites spanning ~430 kilometers of shoreline in coastal Louisiana, Alabama, and Mississippi, using data collected as part of the natural resource damage assessment (NRDA). Our analyses revealed a threshold for oil impacts on marsh edge erosion, with higher erosion rates occurring for ~1-2 years after the spill at sites with the highest amounts of plant stem oiling (90 100%). These results provide compelling evidence showing large-scale ecosystem loss following the Deepwater Horizon oil spill. More broadly, these findings provide rare empirical evidence identifying a geomorphologic threshold in the resistance of an ecosystem to increasing intensity of human-induced disturbance. PMID- 27679957 TI - Transcriptional Analysis Reveals Evidence of Chronically Impeded ECM Turnover and Epithelium-to-Mesenchyme Transition in Scar Tissue Giving Rise to Marjolin's Ulcer. AB - Marjolin's ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma (SCC). This study aimed to elucidate transcriptional changes leading to malignancy by investigating differentially expressed genes in squamous cells present in a SCC compared with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated and a SCC cell line was commercially purchased. mRNA from all three samples was isolated and its expression was quantified using RNASeq. A threshold of log2fold change >2-fold in either direction was considered "differentially expressed." Gene expression analysis revealed distinct differences in gene expression in MU cells compared with EC (665 genes), EC and SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included 1) elevation of genes associated with extracellular matrix organization/degradation, 2) activation of DNA damage, and 3) activation of cytokine signaling. Our analysis revealed two key insights about chronic wound microenvironment conducive to ulceration. First, in EC vs. MU comparison, downregulation of Collagen and Matrix metalloproteinase families suggests chronically impaired extracellular matrix turnover giving rise to a fibrotic microenvironment. Second, in SCC vs. MU comparison, dysregulation of cadherin-mediated cell-cell adhesions is suggestive of epithelial-to-mesenchymal transitions, similar to those during development. Acquisition of epithelial-to mesenchymal transition may underlie the high metastatic rate in MU tumors. Taken together, this sheds light on mechanisms that underlie the divergent clinical features of these cutaneous cancers. PMID- 27679958 TI - Effect of Fireworks Laws on Pediatric Fireworks-Related Burn Injuries. AB - Changes in U.S. fireworks laws have allowed younger children to purchase fireworks. In addition, the changes have allowed individuals to purchase more powerful fireworks. The purpose of this study is to examine the epidemiology of pediatric firework-related burn injuries among a nationally representative sample of the United States for the years 2006 to 2012. We examined inpatient admissions for pediatric firework-related burn patients from 2006 to 2012 using the nationwide inpatient sample and examined emergency department admissions using the nationwide emergency department sample. Both data sources are part of the Healthcare Cost and Utilization Project. Trajectories over time were evaluated. A total of 3193 injuries represented an estimated 90,257 firework-related injuries treated in the United States from 2006 to 2012. A majority of injuries were managed in the emergency department (n = 2008, 62.9%). The incidence generally increased over time; increasing from 4.28 per 100,000 population in 2006 to 5.12 per 100,000 population in 2012, P = .019. However, the proportion of injuries requiring inpatient admission (28.9% in 2006 to 50.0% in 2012, P < .001) and mean length of stay in the hospital (3.12 days in 2006 to 7.35 days in 2012, P < .001) significantly increased over time, while the mean age decreased over time (12.1 year-old in 2006 to 11.4-year-old in 2012, P = .006). The relaxing of U.S. fireworks laws may have had a modest effect on incidence of related injuries and the age of purchaser. However, it has had a dramatic effect on the severity of the related injuries, resulting in more inpatient admissions and longer length of stay in the hospital. Preventative methods should be taken to reduce the rate and severity of firework-related injuries among U.S. youths. PMID- 27679959 TI - Exercise Treadmills: A Cause of Significant Hand Burns in Young Children. AB - A pediatric nurse practitioner and an occupational therapist were impressed by the number and severity of treadmill-related hand burns encountered in their outpatient burn clinic. They observed that treadmill burns appeared to be deeper compared with other contact hand burns. Literature review revealed that research was inadequate in this area. A retrospective chart review was conducted, and a total of 384 patients were found to receive treatments at a regional level 1 pediatric burn center for treadmill and contact hand burns from 2010 to 2014. Age distribution, severity, and negative outcomes were compared between treadmill hand burns and contact hand burns. Recommendations for primary caregivers to prevent treadmill hand burns were given. Treadmill burns were the second most common hand injury mechanism after stovetop burns. Both hot surface contact burns and treadmill burns were more frequently seen in patients 0 to 4 years of age. Treadmill hand burns were more severe than contact hand burns in depth of injury (24.5 vs 1.4% full thickness), need for operative intervention (6.4 vs 0.0%), mean number of burn appointments (4.9 vs 1.9), median time to skin closure (25.2 days vs 11.0 days), and median length of care (51.0 days vs 11.0 days). Treadmill hand burns were frequently seen, and they were more severe and required an increased level and duration of care in comparison with other contact hand burns. PMID- 27679961 TI - Theory-Based Cartographic Risk Model Development and Application for Home Fire Safety. AB - There is a gap in the use of predictive risk models to identify areas at risk for home fires and burn injury. The purpose of this study was to describe the creation, validation, and application of such a model using a sample from an intervention study with parents of newborns in Jefferson County, KY, as an example. Performed was a literature search to identify risk factors for home fires and burn injury in the target population. Obtained from the American Community Survey at the census tract level and synthesized to create a predictive cartographic risk model was risk factor data. Model validation was performed through correlation, regression, and Moran's I with fire incidence data from open records. Independent samples t-tests were used to examine the model in relation to geocoded participant addresses. Participant risk level for fire rate was determined and proximity to fire station service areas and hospitals. The model showed high and severe risk clustering in the northwest section of the county. Strongly correlated with fire rate was modeled risk; the best predictive model for fire risk contained home value (low), race (black), and non high school graduates. Applying the model to the intervention sample, the majority of participants were at lower risk and mostly within service areas closest to a fire department and hospital. Cartographic risk models were useful in identifying areas at risk and analyzing participant risk level. The methods outlined in this study are generalizable to other public health issues. PMID- 27679960 TI - Low Vitamin D Level on Admission for Burn Injury Is Associated With Increased Length of Stay. AB - Currently, there have been few studies that have evaluated the incidence of vitamin D deficiency in adult burn patients or correlated vitamin D levels with burn-related outcomes. The primary objective of the study was to identify the incidence of vitamin D deficiency and insufficiency in an adult burn population. The secondary objective was to determine the impact of vitamin D deficiency and insufficiency on clinical outcomes in burn care. A single-center, retrospective, and observational cohort analysis of adult patients admitted for initial management of burn injury, who had a 25-hydroxyvitamin D (25D) level measured on admission, was performed. Patients were categorized as vitamin D deficient (25D <10 ng/ml), insufficient (10-29 ng/ml), or sufficient (30-100 ng/ml) based on admission measurements. Clinical outcomes including complications, intensive care unit (ICU) and hospital length of stay (LOS), and survival were compared between patients with vitamin D deficiency/insufficiency and patients with vitamin D sufficiency. Three-hundred and eighteen patients were eligible for evaluation. Admission 25D level correlated with deficiency in 46 patients (14.5%), insufficiency in 207 (65.1%), and normal in 65 (20.4%). Patients with vitamin D deficiency or insufficiency experienced higher rates of complications and longer ICU and hospital LOS compared with those with normal vitamin D levels. A large proportion of patients with burn injury presented with vitamin D insufficiency and deficiency which was associated with poor outcomes, including prolonged ICU and hospital LOS. Additional studies are needed to further describe the relationship between vitamin D status and clinical outcomes. PMID- 27679963 TI - Pulmonary hypertension associated with chronic lung diseases. AB - In 2015, the international guidelines for diagnosis and treatment of pulmonary hypertension (PH) were updated. Group 3 of the current classification includes PH associated with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), other pulmonary diseases with restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental lung diseases [1]. PH associated with COPD and ILD is common but difficult to manage, as no long-term randomised controlled trial (RCT) has been conducted with specific pulmonary arterial hypertension (PAH) drugs in PH associated with COPD, and the one recent RCT in PH associated with ILD had to be stopped early due to a possible increased risk of death and side effects in the treatment group. Specific treatment may thus be harmful and may worsen gas exchange as a result of possible recruitment of less oxygenised areas, i.e. by increasing ventilation-perfusion mismatch. Management of PH patients with chronic lung diseases requires careful evaluation and understanding of pathophysiological mechanisms. Interestingly, mediators in PAH and in fibrotic lung disease show some overlaps. Several drugs effective in PAH have been evaluated for anti-fibrotic treatment in ILD, but until today without consistent success. While new drugs with anti-fibrotic effects are now accessible, a specific evidence-based treatment for PH in ILD or COPD with or without emphysema is not yet available. PMID- 27679962 TI - Effects of paroxetine on intravaginal ejaculatory latency time in Egyptian patients with lifelong premature ejaculation as a function of serotonin transporter polymorphism. AB - Premature ejaculation (PE) is a common ejaculatory complaint. The estimated rates among Turkish men reached 20%, although the severest type of PE (lifelong PE) usually does not exceed 2.3%. This could be seen in line with two survey studies involving five nations. They revealed that 2.5% of men had an intravaginal ejaculation latency time of <1 min and 6% of <2 min. Rapid ejaculation may be treated pharmacologically with a variety of different medications that act either centrally or locally to delay ejaculation and subsequent orgasm. Antidepressants, particularly members of the selective serotonin reuptake inhibitor class, retard ejaculation significantly. Recently, it was postulated that men with lifelong PE might result from a combination of polymorphisms of the serotonergic transporter and receptors, and other neurotransmitters and/or receptors. Our findings augment the significant effect of paroxetine in delaying ejaculation in the responders (P<0.001). Meanwhile, the findings do not suggest a positive association between such response and serotonin transporter gene promoter polymorphism. PMID- 27679964 TI - Strategic Planning for Research in Pediatric Critical Care. AB - OBJECTIVE: To summarize the scientific priorities and potential future research directions for pediatric critical care research discussed by a panel of experts at the inaugural Strategic Planning Conference of the Pediatric Trauma and Critical Illness Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. DATA SOURCES: Expert opinion expressed during the Strategic Planning Conference. STUDY SELECTION: Not applicable. DATA EXTRACTION: Chaired by an experienced expert from the field, issues relevant to the conduct of pediatric critical care research were discussed and debated by the invited participants. DATA SYNTHESIS: Common themes and suggested priorities were identified and coalesced. CONCLUSIONS: Of the many pathophysiologic conditions discussed, the multiple organ dysfunction syndrome emerged as a topic in need of more study that is most relevant to the field. Additionally, the experts offered that the interrelationship and impact of critical illness on child development and family functioning are important research priorities. Consequently, long-term outcomes research was encouraged. The expert group also suggested that multidisciplinary conferences are needed to help identify key knowledge gaps to advance and direct research in the field. The Pediatric Critical Care and Trauma Scientist Development National K12 Program and the Collaborative Pediatric Critical Care Research Network were recognized as successful and important programs supported by the branch. The development of core data resources including biorepositories with robust phenotypic data using common data elements was also suggested to foster data sharing among investigators and to enhance disease diagnosis and discovery. Multicenter clinical trials and innovative study designs to address understudied and poorly understood conditions were considered important for field advancement. Finally, the growth of the pediatric critical care research workforce was offered as a priority that could be spawned in many ways including by expanded transdisciplinary and multiprofessional collaboration and diversity representation. PMID- 27679966 TI - Current State of Pediatric Intensive Care and High Dependency Care in Nepal. AB - OBJECTIVES: To describe the state of pediatric intensive care and high dependency care in Nepal. Pediatric intensive care is now a recognized specialty in high income nations, but there are few reports from low-income countries. With the large number of critically ill children in Nepal, the importance of pediatric intensive care is increasingly recognized but little is known about its current state. DESIGN: Survey. SETTING: All hospitals in Nepal that have separate physical facilities for PICU and high dependency care. PATIENTS: All children admitted to these facilities. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A questionnaire survey was sent to the chief of each facility. Eighteen hospitals were eligible and 16 responded. Two thirds of the 16 units were established in the last 5 years; they had a total of 93 beds, with median of 5 (range, 2-10) beds per unit. All 16 units had a monitor for each bed but only 75% could manage central venous catheters and only 75% had a blood gas analyzer. Thirty two percent had only one functioning mechanical ventilator and another 38% had two ventilators, the other units had 3-6 ventilators. Six PICUs (38%) had a nurse-to patient ratio of 1:2 and the others had 1:3 to 1:6. Only one institution had a pediatric intensive care specialist. The majority of patients (88%) came from families with an income of just over a dollar per day. All patients were self funded with a median cost of PICU bed being $25 U.S. dollars (interquartile range, 15-31) per day. The median stay was 6 (interquartile range, 4.8-7) days. The most common age group was 1-5. Sixty percent of units reported respiratory distress/failure as their primary cause for admission. Mortality was 25% (interquartile range, 20-35%) with mechanical ventilation and 1% (interquartile range, 0-5%) without mechanical ventilation. CONCLUSIONS: Pediatric intensive care in Nepal is still in its infancy, and there is a need for improved organization, services, and training. PMID- 27679967 TI - Life-cycle assessment of a Waste-to-Energy plant in central Norway: Current situation and effects of changes in waste fraction composition. AB - Waste-to-Energy (WtE) plants constitute one of the most common waste management options to deal with municipal solid waste. WtE plants have the dual objective to reduce the amount of waste sent to landfills and simultaneously to produce useful energy (heat and/or power). Energy from WtE is gaining steadily increasing importance in the energy mix of several countries. Norway is no exception, as energy recovered from waste currently represents the main energy source of the Norwegian district heating system. Life-cycle assessments (LCA) of WtE systems in a Norwegian context are quasi-nonexistent, and this study assesses the environmental performance of a WtE plant located in central Norway by combining detailed LCA methodology with primary data from plant operations. Mass transfer coefficients and leaching coefficients are used to trace emissions over the various life-cycle stages from waste logistics to final disposal of the ashes. We consider different fractions of input waste (current waste mix, insertion of 10% car fluff, 5% clinical waste and 10% and 50% wood waste), and find a total contribution to Climate Change Impact Potential ranging from 265 to 637gCO2eq/kg of waste and 25 to 61gCO2eq/MJ of heat. The key drivers of the environmental performances of the WtE system being assessed are the carbon biogenic fraction and the lower heating value of the incoming waste, the direct emissions at the WtE plant, the leaching of the heavy metals at the landfill sites and to a lesser extent the use of consumables. We benchmark the environmental performances of our WtE systems against those of fossil energy systems, and we find better performance for the majority of environmental impact categories, including Climate Change Impact Potential, although some trade-offs exist (e.g. higher impacts on Human Toxicity Potential than natural gas, but lower than coal). Also, the insertion of challenging new waste fractions is demonstrated to be an option both to cope with the excess capacity of the Norwegian WtE sector and to reach Norway's ambitious political goals for environmentally friendly energy systems. PMID- 27679969 TI - Enhanced recycling network for spent e-bicycle batteries: A case study in Xuzhou, China. AB - Electric bicycles (e-bicycles) are a primary means of commuting in China because of their light weight, speed, and low maintenance costs. Owing to short service life and environmental pollution hazards, recycling and reuse of e-bicycle batteries has always been a focus of industry and academia. As a typical case of both production and use of large electric bicycles, 113 major sellers, 378 corporate and individual buyers, 147 large e-bicycle repair centers, and 1317 e bicycle owners in Xuzhou City were investigated in order to understand the sales, use, recycling, and disposal of spent e-bicycle batteries. The findings show that the existing distempered recycling system is the main limitation of spent battery recovery, and the actual recovery rate of spent batteries is lower than the estimated output (QW) for the years 2011-2014. Electric bicycle sellers play a fundamental role in the collection of spent batteries in Xuzhou, accounting for 42.3+/-8.3% of all batteries recovered. The widespread use of lithium batteries in recent years has resulted in a reduction in spent battery recycling because of lower battery prices. Furthermore, consumer preferences are another important factor affecting the actual recovery rate according to survey results evaluated using canonical correspondence analysis. In this paper, we suggest that a reverse logistics network system for spent battery recycling should be established in the future; in addition, enhancing producer responsibility, increasing publicity, raising of public awareness, developing green public transport, and reducing dependence on e-bicycles also should be pursued. This study seeks to provide guidance for planning construction and management policies for an effective spent battery recycling system in China and other developing countries. PMID- 27679968 TI - Environmental impact assessment of different end-of-life LCD management strategies. AB - The strong growth of the electrical and electronic equipment production combined with its short lifespan are causing the production of a significant amount of waste to treat. In particular, the present paper focuses on end-of-life liquid crystal displays (LCDs) for their significant content of valuable materials, like plastic, glass and metals that could be recovered after dismantling. In the recent literature, traditional LCD recycling processes are combined with innovative treatments, which allow to recover critical raw materials, such as indium. In this context, we have evaluated the environmental impact of four different strategies of end-of-life LCD management: the disposal in landfilling sites, the incineration, the traditional recycling treatment and an innovative process also addressed to the recovery of indium. The traditional recycling treatment resulted to be the best scenario for the environment. Indeed, a life cycle assessment study gave following environmental burdens (if negative they are credits): 18, 81, -68, -60kg CO2-equiv. and 0.08, 0.01, -0.25, -0.18mol H+ equiv., for the four scenarios in the categories of global warming and acidification, respectively. The limit of the variability of LCD composition was overcome including additional literature data in the study. In order to improve the innovative process sustainability, a system of water recirculation was optimized with a consequent impact decrease of 35% in the global warming category. Nevertheless, this action should be combined with an increase of indium concentration in the panel because the low metal content represents the bottleneck of the overall approach. In this regard, a sensitivity analysis showed that an increase of at least five times in indium concentration in the waste is needed to observe an advantage of the innovative vs the traditional recycling process, when the impact category of climate change is considered. As a whole, the life cycle assessment was confirmed as a key tool for the choice of the best option of WEEE management. PMID- 27679970 TI - Loss of Control Over Eating Scale (LOCES): Validation in undergraduate men and women with and without eating disorder symptoms. AB - The present study aimed to further validate the Loss of Control Over Eating Scale (LOCES) for use with undergraduate men and women with and without eating disorder (ED) symptoms. A total of 261 participants completed the LOCES and the Eating Disorder Examination - Questionnaire (EDE-Q) and were identified as non-clinical or having probable ED symptomatology based on previously used EDE-Q cutoff scores. Results indicated that the LOCES and its subscales were significantly associated with and a significant predictor of global ED pathology and binge episode frequency. The LOCES behavioral subscale appeared to be a stronger predictor of episode frequency compared to other subscales. The ED pathology groups reported significantly higher LOCES scores compared to the non-ED pathology groups. Binary logistic regression analyses revealed that the LOCES was able to accurately distinguish between those with ED pathology and those without ED pathology in the majority of cases. Findings from the present study suggest that the LOCES is highly predictive of ED pathology, strongly associated with ED cognitions and behaviors, and an accurate index for global eating disorder pathology. Future directions for research are discussed. PMID- 27679971 TI - Qualitative meta-synthesis: the experience of chronic pain across conditions. AB - AIM: To synthesize qualitative descriptions of the experience of chronic pain across conditions. BACKGROUND: Chronic pain is a transdiagnostic symptom in that while somatic pathology plays a role in activating pain pathways, psychological and social factors contribute to the experience of pain over time. The treatment of the underlying condition may require both biomedical intervention and biopsychosocial approaches. DESIGN: Qualitative meta-synthesis using Confidence in the Evidence from Reviews of Qualitative Research (CERQual) developed by Grading of Recommendations Assessment Development and Evaluation (GRADE) working group to evaluate the strength of the evidence. DATA SOURCES: PubMed and Ovid Medline from 2000-2015. REVIEW METHODS: Following a systematic search strategy all papers were assessed in relation to inclusion criteria and quality. Themes were extracted from each study and a meta-synthesis conducted before completing an evaluation of confidence in the findings. RESULTS: Forty-one papers exploring the experience of chronic pain were included in the review. Five meta-themes were identified across the studies: 1) the body as obstacle; 2) invisible but real; 3) disrupted sense of self; 4) unpredictability; and 5) keeping going. There was high confidence in the evidence for three themes: 'the body as obstacle'; 'disrupted sense of self' and 'keeping going'; and moderate confidence in the evidence for 'invisible but real' and 'unpredictability'. CONCLUSIONS: The findings in this review suggest there are similarities in the experience of chronic pain across a range of conditions that have implications for the development of transdiagnostic pain management strategies and interventions. PMID- 27679972 TI - The alpha7 nicotinic acetylcholine receptor agonist tropisetron counteracts ultraviolet A-mediated oxidative stress in human dermal fibroblasts. PMID- 27679973 TI - Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress. AB - The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6 hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77. Nur77 activation further decreased cell viability, aggravated intracellular LDH release, intracellular Ca2+, ROS levels, apoptosis, ER tress and, mitochondrial transmembrane potential (DeltaPsim) decline. In addition, Nur77 activation significantly enhanced the efficiency of autophagy as indicated by an up-regulation of Beclin-1/LC-3 and downregulation of p62, and aggravated mitochondrial dysfunctions and ER stress as shown by increased HSP60/Cytochrome C (Cyt C) and CHOP-ATF3 levels respectively. These changes could be partially reversed by Nur77 knockdown. Moreover, Nur77 activation upregulated PINK1 and downregulated Parkin levels. We conclude that Nur77 exacerbates PC12 cell death at least partially by aggravating the mitochondrial impairment and ER stress and enhancing autophagy. We propose that Nur77 is likely a critical target in the PD therapy. PMID- 27679974 TI - Long sleep duration, independent of frailty and chronic Inflammation, was associated with higher mortality: A national population-based study. AB - AIM: There is a complex interrelationship between long sleep duration, frailty, chronic inflammation and mortality among the community-dwelling middle-aged and elderly population, which remains unclear and deserves to be investigated. The current study intended to explore these associations by using a prospective population-based cohort study. METHODS: A total of 937 community-dwelling middle aged and elderly people were enrolled. Sleep patterns of the study participants were categorized as short (<6 h), average or long (>=8 h). Sleep disturbance was defined by daytime dysfunction defined by the Pittsburg Sleep Quality Index. Frailty was defined as three or more phenotypes of Fried's Frailty. RESULTS: During an average of 4.7 years follow up, 72 (7.7%) study participants died. The adjusted hazard ratio (HR) for death of long sleepers was 2.42 (95% confidence interval [CI] 1.38-4.27), HR of long sleepers plus frailty was 2.37 (95% CI 1.35 4.19) and HR of long sleepers plus log interleukin-6 was 2.11 (95% CI 1.19-3.76). Adjusted HR of daytime dysfunction was 1.79 (95% CI 1.09-2.94). The association between daytime dysfunction and mortality became statistical insignificant after further adjustment for frailty. CONCLUSIONS: Long sleep duration, independent of frailty and interleukin-6, was associated with 5-year mortality in older adults. The relationship between daytime dysfunction and death diminished after adjusting for frailty. Geriatr Gerontol Int 2017; 17: 1481-1487. PMID- 27679975 TI - Multifaceted role of hair follicle dermal cells in bioengineered skins. AB - BACKGROUND: The method of generating bioengineered skin constructs was pioneered several decades ago; nowadays these constructs are used regularly for the treatment of severe burns and nonhealing wounds. Commonly, these constructs are comprised of skin fibroblasts within a collagen scaffold, forming the skin dermis, and stratified keratinocytes overlying this, forming the skin epidermis. In the past decade there has been a surge of interest in bioengineered skins, with researchers seeking alternative cell sources, or scaffolds, from which constructs can be established, and for more biomimetic equivalents with skin appendages. OBJECTIVES: To evaluate whether human hair follicle dermal cells can act as an alternative cell source for engineering the dermal component of engineered skin constructs. METHODS: We established in vitro skin constructs by incorporating into the collagenous dermal compartment: (i) primary interfollicular dermal fibroblasts, (ii) hair follicle dermal papilla cells or (iii) hair follicle dermal sheath cells. In vivo skins were established by mixing dermal cells and keratinocytes in chambers on top of immunologically compromised mice. RESULTS: All fibroblast subtypes were capable of supporting growth of overlying epithelial cells, both in vitro and in vivo. However, we found hair follicle dermal sheath cells to be superior to fibroblasts in their capacity to influence the establishment of a basal lamina. CONCLUSIONS: Human hair follicle dermal cells can be readily interchanged with interfollicular fibroblasts and used as an alternative cell source for establishing the dermal component of engineered skin both in vitro and in vivo. PMID- 27679976 TI - Narrowing the focus on the assessment of psychosis-related PTSD: a methodologically orientated systematic review. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) in response to psychosis and associated experiences (psychosis-related PTSD, or PR-PTSD) is the subject of a growing field of research. However, a wide range of PR-PTSD prevalence rates has been reported. This may be due to definitional and methodological inconsistencies in the assessment of PR-PTSD. OBJECTIVE: The focus of the review is two-fold. (1) To identify factors that enhance, or detract from, the robustness of PR-PTSD assessment and (2) to critically evaluate the evidence in relation to these identified criteria, including the impact on PR-PTSD prevalence rates. METHOD: Four quality criteria, whose development was informed by mainstream PTSD research, were selected to evaluate findings on PR-PTSD prevalence. Two criteria related to assessment of psychosis-related stressors (participant identification of worst moments of discrete threat events; psychometrically robust trauma measure) and two focussed on PR-PTSD symptom measurement (adequate time elapsed since trauma; use of validated PTSD interview) in the context of psychosis. RESULTS: Twenty-one studies of PR-PTSD, with prevalence rates ranging from 11 to 51%, were evaluated. Fourteen studies (67%) used robust PTSD measures but PR trauma was not specifically defined or assessed with validated measures. Eleven studies (52%) assessed PTSD before sufficient time had elapsed since the trauma. Due to significant methodological limitations, it was not possible to review PR PTSD rates and provide a revised estimate of prevalence. CONCLUSIONS: Methodological limitations are common in existing studies of PR-PTSD prevalence. Specific recommendations for improving assessment of psychosis-related trauma are made to guide the development of this new and emerging field. The review concludes with a proposed conceptualisation of PR-PTSD in the context of current diagnostic systems. The utility of the PR-PTSD term and its theoretical underpinnings are discussed. PMID- 27679977 TI - Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey-Holden Prostate Cancer Academy Meeting. AB - INTRODUCTION: The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. METHODS: For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer. The 2016 CHPCA Meeting was attended by 71 investigators from prostate cancer and other fields, who discussed the biology, study methodologies, treatment strategies, and critical unmet needs concerning metastatic prostate cancer, with the ultimate goal of advancing strategies to treat and eliminate this disease. RESULTS: The major topics of discussion included: the molecular landscape and molecular heterogeneity of metastatic prostate cancer, the role of the metastatic microenvironment, optimizing immunotherapy in metastatic prostate cancer, learning from exceptional responders and non-responders, targeting DNA repair deficiency in advanced prostate cancer, developing and applying novel biomarkers and imaging techniques, and potential roles for the microbiome in prostate cancer. DISCUSSION: This article reviews the topics presented and discussions held at the CHPCA Meeting, with a focus on the unknowns and next steps needed to advance our understanding of the biology and most effective treatment strategies for metastatic prostate cancer. Prostate 77:123-144, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27679978 TI - Functional gastrointestinal disorders in Greek Children based on ROME III criteria: identifying the child at risk. AB - BACKGROUND: Functional gastrointestinal disorders (FGIDs) are a common, diverse group of disorders of unknown etiology, resulting in significant socieconomic burden. In this study, we aimed to assess the prevalence of FGIDs in children aged 6-18 years and examine their association with various demographic and socioeconomic parameters. METHODS: This was a school-based, cross-sectional study approved by the relevant government authorities. Informed consent was obtained by the legal representatives of all children who participated. Diagnoses of FGIDs were based on the Greek official translation of the ROME-III questionnaire. Demographic and socioeconomic information were also collected. KEY RESULTS: A total of 1588 children (51.8% females, mean age: 12.9+/-2.8 years) were included. The overall prevalence of any-FGID was 23.1% (95% CI: 21.1-25.2). The most common FGIDs were functional constipation, n=231 (13.9%), abdominal migraine, n=84 (5.6%), aerophagia, n=58 (3.5%), and irritable bowel syndrome, n=48 (3.0%). Multiple logistic regression analysis on the probability of any-FGID identified physical exercise, TV-exposure, victimization, gender, parental educational level, number of children at home and number of adults at home as significant covariates for any-FGID in the final model. CONCLUSIONS AND INFERENCES: FGIDs affect approximately 1 in 4 school-aged children in Greece. The following characteristics are associated with a higher probability of any-FGID: female gender, living in a non-nuclear household, victimization, lower parental education level, infrequent physical activity, and high television exposure. PMID- 27679979 TI - Structure-based discovery of two antiviral inhibitors targeting the NS3 helicase of Japanese encephalitis virus. AB - Japanese encephalitis virus (JEV) is a flavivirus that threatens more than half of the world's population. Vaccination can prevent the disease, but no specific antiviral drug is yet available for clinical therapy, and the death rate caused by JEV can reach as high as 60%. The C-terminus of non-structural protein 3 (NS3) of flavivirus encodes helicase and has been identified as a potential drug target. In this study, high throughput molecular docking was employed to identify candidate JEV NS3 helicase inhibitors in a commercial library containing 250,000 compounds. Forty-one compounds were then tested for their ability to inhibit NS3 activity. Two compounds inhibited unwinding activity strongly but had no effect on the ATPase activity of the protein. Western blots, IFA, and plaque reduction assays demonstrated that both compounds inhibited the virus in cell culture. The EC50s of the two compounds were 25.67 and 23.50 MUM, respectively. Using simulated docking, the two compounds were shown to bind and block the NS3 RNA unwinding channel, consistent with the results of the enzyme inhibition tests. The atoms participating in intramolecular interaction were identified to facilitate future compound optimization. PMID- 27679981 TI - Short-Term Prospective Clinical Evaluation of Monolithic and Partially Veneered Zirconia Single Crowns. AB - OBJECTIVES: The purpose of this study was to prospectively evaluate the short term clinical performance and esthetics of monolithic and partially (i.e., facially) veneered zirconia single crowns (MZC and PZC, respectively). METHODS: Between September 2011 and June 2013, 68 participants received 90 MZCs and 72 PZCs. Clinical study documentation was performed at crown cementation (baseline), at the 6-month follow-up, and then yearly thereafter using standardized report forms. Eight participants with 14 single crowns (eight MZCs and six PZCs) dropped out during clinical follow-up. Thus, 60 participants (28 male, mean age 62.5 +/- 13.1 years) fitted with 82 MZCs and 66 PZCs were analyzed in February 2016 (Kaplan-Meier survival; mean observation time for the restorations 35.1 +/- 6.3 months). Descriptive statistics were calculated for participants' and dentists' esthetic ratings on a numerical rating scale from 0 to 10 (0 = unacceptable color and shape; 10 = excellent color and shape). RESULTS: Complications were predominantly biological in nature. One PZC was affected by minor chipping. Cumulative 3-year failure-free survival was 98.5% (standard error (SE), 1.5%) for both MZCs and PZCs. Three-year cumulative complication-free survival (success) was 93.6% (SE 2.8%) for MZCs and 95.5% (SE 2.6%) for PZCs. Three-year cumulative fracture-free survival was 100% for MZCs and 98.5% (SE 1.5%) for PZCs. Crowns of both types were awarded high esthetic scores by participants and dentists. CONCLUSIONS: Monolithic and partially veneered zirconia crowns can be used clinically with excellent short-term survival and success and without compromising esthetic appearance. Longer-term follow-up is, however, desirable. CLINICAL SIGNIFICANCE: During the observation time, both monolithic and partially veneered zirconia crowns showed an outstanding low technical complication rate: only one minor chipping and three losses of retention were observed. Additionally, esthetics was excellent. Based on these results the clinical use of this kind of restoration is promising. (J Esthet Restor Dent 29:22-30, 2017). PMID- 27679980 TI - Pannexin3 inhibits TNF-alpha-induced inflammatory response by suppressing NF kappaB signalling pathway in human dental pulp cells. AB - Human dental pulp cells (HDPCs) play a crucial role in dental pulp inflammation. Pannexin 3 (Panx3), a member of Panxs (Pannexins), has been recently found to be involved in inflammation. However, the mechanism of Panx3 in human dental pulp inflammation remains unclear. In this study, the role of Panx3 in inflammatory response was firstly explored, and its potential mechanism was proposed. Immunohistochemical staining showed that Panx3 levels were diminished in inflamed human and rat dental pulp tissues. In vitro, Panx3 expression was significantly down-regulated in HDPCs following a TNF-alpha challenge in a concentration dependent way, which reached the lowest level at 10 ng/ml of TNF-alpha. Such decrease could be reversed by MG132, a proteasome inhibitor. Unlike MG132, BAY 11 7082, a NF-kappaB inhibitor, even reinforced the inhibitory effect of TNF-alpha. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to investigate the role of Panx3 in inflammatory response of HDPCs. TNF-alpha-induced pro-inflammatory cytokines, interleukin (IL)-1beta and IL-6, were significantly lessened when Panx3 was overexpressed in HDPCs. Conversely, Panx3 knockdown exacerbated the expression of pro-inflammatory cytokines. Moreover, Western blot, dual-luciferase reporter assay, immunofluorescence staining, qRT-PCR and ELISA results showed that Panx3 participated in dental pulp inflammation in a NF-kappaB-dependent manner. These findings suggested that Panx3 has a defensive role in dental pulp inflammation, serving as a potential target to be exploited for the intervention of human dental pulp inflammation. PMID- 27679982 TI - A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force. AB - Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG.protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG.protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices. PMID- 27679983 TI - Health Care Expenditure and Income: A Global Perspective. AB - This paper investigates the long-run economic relationship between healthcare expenditure and income in the world using data on 167 countries over the period 1995-2012, collected from the World Bank data set. The analysis is carried using panel data methods that allow one to account for unobserved heterogeneity, temporal persistence, and cross-section dependence in the form of either a common factor model or a spatial process. We estimate a global measure of income elasticity using all countries in the sample, and for sub-groups of countries, depending on their geo-political area and income. Our findings suggest that at the global level, health care is a necessity rather than a luxury. However, results vary greatly depending on the sub-sample analysed. Our findings seem to suggest that size of income elasticity depends on the position of different countries in the global income distribution, with poorer countries showing higher elasticity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27679984 TI - The flagellar motor adapts, optimizing bacterial behavior. AB - A short review is given of recent work showing that the flagellar rotary motor of the bacterium Escherichia coli remodels to match its operating point (the fraction of time that it spins clockwise) to the requirements of the chemotaxis signaling network, and to provide the torque necessary to operate at different viscous loads. PMID- 27679985 TI - Clinical presentation and outcomes for adult ependymoma patients. AB - BACKGROUND: Outcomes projects can be a catalyst for determining disease- and treatment-related consequences for patients with rare tumors. The Adult Ependymoma Outcomes (AEO) survey uses self-reported experience to evaluate how this tumor affects patient groups throughout the illness trajectory. METHODS: Patients completed the AEO survey via a Web-based portal. The survey included questions on treatment, tumor recurrence, and current health status; the MD Anderson Symptom Inventory Brain Tumor and Spine Tumor modules; and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: The sample included 264 participants (57% female) with a median age of 46 years (range, 18 77 years). Radiation treatment was commonly used for patients who had brain involvement (chi2 (1) = 20.7; P < .001), underwent a partial resection (43%; chi2 (3) = 15.4; P < .001), or had a grade 3 tumor (41%; chi2 (2) = 18.8; P < .001). Recurrence occurred in a small group (29%), with grade 1 tumor patients 2.6 times more likely and grade 3 tumor patients 2.5 times more likely to experience recurrence than those with grade 2 tumors. Spine tumor patients had a higher symptom burden (mean, 2.8; scale, 0-10) than brain tumor patients (t(247) = 4.0), and they reported more moderate to severe symptoms (rating >= 5; 29%) than their counterparts (18%). Within the physical health portion of the SF-36, spine tumor patients reported worse health with respect to bodily pain (t(249) = 6.8; P < .001), physical functioning (t(252) = 4.1; P < .001), and vitality (t(202.2) = 3.0; P < .003). CONCLUSIONS: These results demonstrate the feasibility of implementing outcomes projects that report on the clinical and demographic characteristics of a rare patient population, and they underscore the importance of outcomes data in understanding disease-related issues. Cancer 2017;123:494 501. (c) 2016 American Cancer Society. PMID- 27679987 TI - Identification of a novel HLA-B*50 allele, HLA-B*50:01:08, in a Spanish hematological patient. AB - HLA-B*50:01:08 differs from B*50:01:01 at nucleotides g.1206T>A (intron 3) and g.1658G>A (exon 4). PMID- 27679986 TI - Structure-Function Correlations of Poly(Amido Amine)s for Gene Delivery. AB - Poly(amido amine)s' (PAAs) versatility are nearly unique among stepwise polymers. Different functional groups can be easily introduced into these polymers to add functionality such as cell internalization, charge-shift, bioreducibility, "stealth" properties, and targeting moieties, while maintaining the bulk structural integrity of these polymers. The poly(amido amine)s are used as a unique research platform to elucidate their complex structure-function relationship. It is shown that guanidinium group, carboxyl group, disulfide bond, alkyl chain, branching, acetyl groups, benzoyl groups, and quaternary nicotinamide moieties can influence many steps of gene delivery, such as DNA condensation, cellular uptake, endosomal escape, nuclear entry, and finally gene expression. The authors systematically discuss the structure-function correlations of PAAs for gene delivery, and elaborate how the properties of polymers can be adjusted by changing the polymeric structure. PMID- 27679988 TI - Genetic divergence among invasive and native populations of the yellow peacock cichlid Cichla kelberi. AB - This study used the hypervariable domain of the mitochondrial DNA (mtDNA) control region (CR) to assess the genetic divergence among native and invasive populations of Cichla kelberi, which is considered the first peacock cichlid introduced and established throughout Brazil and is among the most invasive populations of this genus worldwide. The maximum likelihood tree based on 53 CR sequences with strong bootstrap support revealed that C. kelberi forms a monophyletic clade, confirming that all 30 C. kelberi studied belong to this morphotype. Additionally, the haplotype analysis of the C. kelberi sequences from 11 sampling sites revealed that invasive populations are much less diverse than native ones and largely dominated by a single haplotype that prevailed in reservoirs at the Paraiba do Sul River basin. Two haplotypes were recorded exclusively in an invasive population at Porto Rico, southern Brazil, and one private haplotype was detected in two reservoirs from Paraiba do Sul (Pereira Passos and Paracambi), suggesting more than one introduction event and that native populations should be better evaluated to encompass the entire genetic diversity of native C. kelberi. The possible route and pathways of C. kelberi introduction are also briefly discussed. PMID- 27679989 TI - High correlation between performance on a virtual-reality simulator and real-life cataract surgery. AB - PURPOSE: To investigate the correlation in performance of cataract surgery between a virtual-reality simulator and real-life surgery using two objective assessment tools with evidence of validity. METHODS: Cataract surgeons with varying levels of experience were included in the study. All participants performed and videorecorded three standard cataract surgeries before completing a proficiency-based test on the EyeSi virtual-reality simulator. Standard cataract surgeries were defined as: (1) surgery performed under local anaesthesia, (2) patient age >60 years, and (3) visual acuity >1/60 preoperatively. A motion tracking score was calculated by multiplying average path length and average number of movements from the three real-life surgical videos of full procedures. The EyeSi test consisted of five abstract and two procedural modules: intracapsular navigation, antitremor training, intracapsular antitremor training, forceps training, bimanual training, capsulorhexis and phaco divide and conquer. RESULTS: Eleven surgeons were enrolled. After a designated warm-up period, the proficiency-based test on the EyeSi simulator was strongly correlated to real life performance measured by motion-tracking software of cataract surgical videos with a Pearson correlation coefficient of -0.70 (p = 0.017). CONCLUSION: Performance on the EyeSi simulator is significantly and highly correlated to real life surgical performance. However, it is recommended that performance assessments are made using multiple data sources. PMID- 27679991 TI - Medication-induced acute esophageal necrosis: a case report. AB - BACKGROUND: Acute esophageal necrosis or Gurvits syndrome is a rare clinical condition characterized by necrotic esophageal mucosa with an abrupt end at the gastroesophageal junction. Its etiology is multifactorial, but mainly related to low-flow states. We describe a case in which a patient accidentally took the wrong medication, with clozapine and olanzapine most probably being the cause of his subsequent acute esophageal necrosis. This situation is, to the best of our knowledge, unprecedented in the medical literature. CASE PRESENTATION: A 65-year old Finnish male patient with schizoaffective disorder accidentally took another patient's medication, including clozapine 300 mg, olanzapine 30 mg, teofyllamine 200 mg, warfarin 5 mg, and potassium chloride 1 g. He arrived at our hospital for a routine examination 6 h after the incident. At hospital he started to vomit brownish liquid and had tachycardia and fever. Gastroparesis was found. An endoscopy revealed necrotic esophageal mucosa that was typical for Gurvits syndrome. A computed tomography scan showed an edematous esophagus and raised suspicion of a proximal jejunal obstruction. A laparotomy was performed but only healthy paralytic bowel was found. Our patient healed uneventfully within a week. CONCLUSIONS: There are analogous case reports describing ischemic colitis associated with the use of clozapine and olanzapine, but none describing the same for the other medications our patient took. We believe that in this case clozapine and olanzapine caused acute esophageal necrosis and this possibility should be taken into account when treating patients with acute ischemic enteropathy. PMID- 27679990 TI - Sources of information on Gestational Diabetes Mellitus, satisfaction with diagnostic process and information provision. AB - BACKGROUND: This study aimed to investigate the percentage of the needs and expectations of pregnant women with Gestational Diabetes Mellitus (GDM) about the best sources of information on GDM, their satisfaction with the diagnostic process and information provision. METHODS: Questionnaires were completed by 116 pregnant women aged 18-45 years, diagnosed with GDM and recruited from maternity diabetes clinic. Eligible women were invited to participate in the study and informed consent was obtained from each participant prior to enrolment. Descriptive statistics, Kruskal-Wallis test, t-test and chi-square test were used to analyse data. RESULTS: Most women (64.2 %) expected general practitioners (GPs) to be the best source of GDM information, following by diabetes educator nurses (45.9 %), diabetes support groups (33.9 %) and internet (32.1 %). However, women found that diabetes educator nurses were more helpful than GPs (32.6 and 20.2 %, respectively). Participants' age and country of birth were statistically significant. For women aged over 30 years and women born overseas the internet was the most useful information source (68.9 and 77.1 % respectively). Overall, women were very satisfied (33.0 %) or satisfied (45.0 %) with how they were informed of the GDM diagnosis, although 26.0 % were informed by telephone and 16.0 % by text message. More than one-third (39.0 %) of women were not referred to sources of information by GPs at time of diagnosis of GDM (p <0.0001). Women who were referred reported that they were very satisfied (40.0 %) or satisfied (44.0 %) with information they received. Only 8.0 % of women reported dissatisfaction with the manner of health professionals. CONCLUSION: The results suggest that health professionals should be aware of the needs and expectations of women who have been diagnosed with GDM, with most women expecting to receive information on GDM from their GPs and diabetes educator nurses. The findings suggest that there is scope for improving how women are informed of the GDM diagnosis and given information, and in clinicians' manner. PMID- 27679965 TI - Pediatric Out-of-Hospital Cardiac Arrest Characteristics and Their Association With Survival and Neurobehavioral Outcome. AB - OBJECTIVE: To investigate relationships between cardiac arrest characteristics and survival and neurobehavioral outcome among children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial. DESIGN: Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial data. SETTING: Thirty-six PICUs in the United States and Canada. PATIENTS: All children (n = 295) had chest compressions for greater than or equal to 2 minutes, were comatose, and required mechanical ventilation after return of circulation. INTERVENTIONS: Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting prearrest status) and 12 months postarrest. U.S. norms for Vineland Adaptive Behavior Scales, Second Edition scores are 100 (mean) +/- 15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. MEASUREMENT AND MAIN RESULTS: Cardiac etiology of arrest, initial arrest rhythm of ventricular fibrillation/tachycardia, shorter duration of chest compressions, compressions not required at hospital arrival, fewer epinephrine doses, and witnessed arrest were associated with greater 12 month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Weekend arrest was associated with lower 12-month survival. Body habitus was associated with 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70; underweight children had better outcomes, and obese children had worse outcomes. On multivariate analysis, acute life threatening event/sudden unexpected infant death, chest compressions more than 30 minutes, and weekend arrest were associated with lower 12-month survival; witnessed arrest was associated with greater 12-month survival. Acute life threatening event/sudden unexpected infant death, other respiratory causes of arrest except drowning, other/unknown causes of arrest, and compressions more than 30 minutes were associated with lower 12 month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. CONCLUSIONS: Many factors are associated with survival and neurobehavioral outcome among children who are comatose and require mechanical ventilation after out-of-hospital cardiac arrest. These factors may be useful for identifying children at risk for poor outcomes, and for improving prevention and resuscitation strategies. PMID- 27679992 TI - Antimicrobial Susceptibility Patterns of Recent Cuban Mycoplasma genitalium Isolates Determined by a Modified Cell-Culture-Based Method. AB - Isolation of Mycoplasma genitalium from clinical specimens remains difficult and few strains are available for antimicrobial susceptibility testing. We describe the antimicrobial susceptibility of M. genitalium strains grown in Vero cell culture with first- and second- line antibiotics, using a modified cell-culture based method. Macrolide- and -fluoroquinolone resistance determinants were detected by sequencing of the 23S and parC genes, respectively. Seven strains were examined, including three new, genetically distinct M. genitalium strains isolated from endocervical and urethral swab specimens from Cuban patients together with four reference strains isolated from specimens collected from men in Denmark, Sweden and Australia. Azithromycin was the most active drug against two of the Cuban M. genitalium strains with MICs values of 0.008 mg/liter, however, one strain was macrolide resistant with an MIC of >8 mg/liter, and the A2059G resistant genotype. Ciprofloxacin was the least active antimicrobial drug and moxifloxacin was the most active fluoroquinolone against the new clinical strains, although an MIC of 1 mg/l was found for two strains. However, no relevant parC mutations were detected. MICs for tetracyclines were 0.5-4 mg/liter. Although the number of Cuban strains was low, the results suggest that a single-dose azithromycin treatment could be ineffective, and that a second-line treatment with moxifloxacin, should become an option in Cuba. To our knowledge, this is the first report of isolation and antibiotic susceptibility testing of M. genitalium strains from the Latin-American region, and the first detection of macrolide resistance in such strains. PMID- 27679994 TI - A New Emissive Chalcone-Based Chemosensor Armed by Coumarin and Naphthol with Fluorescence "Turn-on" Properties for Selective Detection of F- Ions. AB - A new chalcone-based probe containing coumarin and naphthol at both ends has been synthesized via aldol condensation. The uniqueness of the newly derived probe can be ascribed to the presence of naphthol and coumarin units acting as binding site and signaling element, respectively. The fluorogenic behaviors toward various anions were investigated. The probe was characterized by various spectroscopic techniques and the in-depth study led to show excellent selectivity and sensitivity for fluoride ions. The hydrogen bonding thus formed with fluoride anion provides remarkable fluorometric responses. The interactions of the probe with fluoride ions were determined by fluorescence, FT-IR and NMR spectroscopic techniques. The exploratory studies by fluorescent spectral changes augur well for the naked-eye sensing applications. PMID- 27679993 TI - Green Synthetic Approach for Synthesis of Fluorescent Carbon Dots for Lisinopril Drug Delivery System and their Confirmations in the Cells. AB - In this work, highly luminescent carbon dots (CDs) were synthesized by the hydrothermal method at 170 degrees C for 12 h using pasteurized milk as a carbon source. The prepared CDs exhibited bright blue fluorescence under UV light illumination at 365 nm. The CDs show fluorescence life time of ~4.89 ns at excitation wavelength of 370 nm. The effect of different solvents on the fluorescence property of CDs was also investigated. The lisinopril (Lis)-loaded CDs were fabricated by self-assembly of lisinopril on the surfaces of CDs, which were characterized by UV-visible and FT-IR spectroscopic techniques. The controlled release of lisinopril from the Lis-CDs was realized at pH values of 5.2, 6.2 and 7.4, respectively. The results of the cytotoxicity and confocal laser scanning microscopic images indicate that the Lis-CDs were successfully uptaken by HeLa cells without apparent cytotoxicity. The synthesized CDs show great potential as drug vehicles with good biocompatibility, sustained release of lisinopril from CDs, indicating that the CDs can act as a promising drug delivery system for therapeutic delivery and/or bioimaging applications. PMID- 27679995 TI - New ATP8A2 gene mutations associated with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. AB - We report the clinical and biochemical findings from two unrelated patients who presented with a novel syndrome: encephalopathy, intellectual disability, severe hypotonia, chorea and optic atrophy. Whole exome sequencing (WES) uncovered a homozygous mutation in the ATP8A2 gene (NM_016529:c.1287G > T, p.K429N) in one patient and compound heterozygous mutations (c.1630G > C, p.A544P and c.1873C > T, p.R625W) in the other. Only one haploinsufficiency case and a family with a homozygous mutation in ATP8A2 gene (c.1128C > G, p.I376M) have been described so far, with phenotypes that differed slightly from the patients described herein. In conclusion, our data expand both the genetic and phenotypic spectrum associated with ATP8A2 gene mutations. PMID- 27679996 TI - Defining the genetic basis of early onset hereditary spastic paraplegia using whole genome sequencing. AB - We performed whole genome sequencing (WGS) in nine families from India with early onset hereditary spastic paraplegia (HSP). We obtained a genetic diagnosis in 4/9 (44 %) families within known HSP genes (DDHD2 and CYP2U1), as well as perixosomal biogenesis disorders (PEX16) and GM1 gangliosidosis (GLB1). In the remaining patients, no candidate structural variants, copy number variants or predicted splice variants affecting an extended candidate gene list were identified. Our findings demonstrate the efficacy of using WGS for diagnosing early-onset HSP, particularly in consanguineous families (4/6 diagnosed), highlighting that two of the diagnoses would not have been made using a targeted approach. PMID- 27679997 TI - Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk study. AB - BACKGROUND: Despite convincing evidence in the Mediterranean region, the cardiovascular benefit of the Mediterranean diet is not well established in non Mediterranean countries and the optimal criteria for defining adherence are unclear. The population attributable fraction (PAF) of adherence to this diet is also unknown. METHODS: In the UK-based EPIC-Norfolk prospective cohort, we evaluated habitual diets assessed at baseline (1993-1997) and during follow-up (1998-2000) using food-frequency questionnaires (n = 23,902). We estimated a Mediterranean diet score (MDS) using cut-points projected from the Mediterranean dietary pyramid, and also three other pre-existing MDSs. Using multivariable adjusted Cox regression with repeated measures of MDS and covariates, we examined prospective associations between each MDS with incident cardiovascular diseases (CVD) by 2009 and mortality by 2013, and estimated PAF for each outcome attributable to low MDS. RESULTS: We observed 7606 incident CVD events (2818/100,000 person-years) and 1714 CVD deaths (448/100,000). The MDS based on the Mediterranean dietary pyramid was significantly associated with lower incidence of the cardiovascular outcomes, with hazard ratios (95 % confidence intervals) of 0.95 (0.92-0.97) per one standard deviation for incident CVD and 0.91 (0.87-0.96) for CVD mortality. Associations were similar for composite incident ischaemic heart disease and all-cause mortality. Other pre-existing MDSs showed similar, but more modest associations. PAF due to low dietary pyramid based MDS (<95th percentile) was 3.9 % (1.3-6.5 %) for total incident CVD and 12.5 % (4.5-20.6 %) for CVD mortality. CONCLUSIONS: Greater adherence to the Mediterranean diet was associated with lower CVD incidence and mortality in the UK. This diet has an important population health impact for the prevention of CVD. PMID- 27679998 TI - The accumulation and health risk of heavy metals in vegetables around a zinc smelter in northeastern China. AB - Mining and smelting activities engender soil contamination by metals severely. A field survey was conducted to investigate the present situation and health risk of heavy metals (Cd, Pb, Zn, Cu, Cr, As, and Hg) in soils and vegetables in the surrounding area of an 80-year-old zinc smelter in northeastern China. Soil pH, organic matter (SOM), and cation exchange capacity (CEC) were determined, and their relations with heavy metal contents in edible parts of vegetables were analyzed. Results showed that the smelting had led to the significant contamination of the local soils by Cd and Zn, with average concentrations of 3.88 and 403.89 mg kg-1, respectively. Concentrations of Cd and Zn in greenhouse soils were much lower than those in open farmland soils. Cd concentrations in vegetable edible parts exceeded the permissible limits severely, while other metal concentrations were much lower than the corresponding standards. Leaf and root vegetables had higher concentrations and bioaccumulation factors (BCFs) of Cd than fruit vegetables. Hazard quotient and hazard index showed that cadmium is imposing a health risk to local residents via vegetable consumption. Cd uptake of some vegetables can be predicted by empirical models with the following parameters: soil pH, SOM, CEC, Zn concentrations, and Cd concentrations. Vegetables such as cabbage, Chinese cabbage, tomato, cucumber, and green bean were screened out as being suitable to grow in the studied area. PMID- 27679999 TI - Monitoring of emerging pollutants in Guadiamar River basin (South of Spain): analytical method, spatial distribution and environmental risk assessment. AB - Guadiamar River is located in the southwest of the Iberian Peninsula and connects two protected areas in the South of Spain: Sierra Morena and Donana National Park. It is sited in an area affected by urban, industrial and agriculture sewage pollution and with tradition on intensive mining activities. Most of the studies performed in this area have been mainly focused on the presence of heavy metals and, until now, little is known about the occurrence of other contaminants such as emerging organic pollutants (EOPs). In this work, an analytical method has been optimized and validated for monitoring of forty-seven EOPs in surface water. The analytical method has been applied to study the distribution and environmental risk of these pollutants in Guadiamar River basin. The analytical method was based on solid-phase extraction and determination by liquid chromatography-triple quadrupole-tandem mass spectrometry. The 60 % of the target compounds were found in the analyzed samples. The highest concentrations were found for two plasticizers (bisphenol A and di(2-ethyhexyl)phthalate, mean concentration up to 930 ng/L) and two pharmaceutical compounds (caffeine (up to 623 ng/L) and salicylic acid (up to 318 ng/L)). This study allowed to evaluate the potential sources (industrial or urban) of the studied compounds and the spatial distribution of their concentrations along the river. Environmental risk assessment showed a major risk on the south of the river, mainly due to discharges of wastewater effluents. PMID- 27680000 TI - Comparative study of phosphorus adsorption behaviors in lake sediments over short and long periods of time: implication for the prediction of the release of phosphorus by CaCl2 and NaHCO3 extraction. AB - Ten sediments were collected from the northern part of Taihu Lake, China. They were incubated for 24 h and 80 days to analyze the adsorption characteristics. After adsorption, the residual sediments were extracted with 0.01 M CaCl2 and 0.5 M NaHCO3 separately. Maximum buffer capacities of the Langmuir and Freundlich functions of 80-day incubation were highly correlated with 24 h (R 2 = 0.97). A longer time would enhance the resistance of the sediments to P changes in the water. Adsorption and NaHCO3-P were highly linearly related with R 2 > 0.969, but the relationships between 24 h and 80 days were different. The relationships between adsorption and CaCl2-P could be better explained (97 %) by segmented line models, but the fitting results were affected by incubation time. An interesting finding is that when we plotted the NaHCO3-P and CaCl2-P together by a segmented line model, the data showed a uniform trend unrelated to the incubation time. NaHCO3-P is seldom used to evaluate P status in sediments in comparison with soils. Yet, our results suggested NaHCO3-P is a good bridge to link the sediments P retention ability and P release risk. Due to its simplicity, NaHCO3-P has promising potential in predicting the transfer of P from sediments. PMID- 27680001 TI - Study of the antimicrobial and antifouling properties of different oxide surfaces. AB - Membrane separation processes find applications in an array of fields as they use far less energy and chemical agents than competing processes. However, a major drawback of membrane technology is that biofilm formation alters membrane performances. Preventing biofilm formation is thus a pivotal challenge for larger scale development of membrane processes. Here, we studied the comparative antibacterial activities of different inorganic membranes (ceramic and zeolite coated ceramic with or without copper exchange) using several bacterial strains (Escherichia coli, Staphylococcus aureus, and Bacillus subtilis). In static conditions, alumina plates coated with Cu-exchanged zeolite showed significant bactericidal activity. In dynamic mode (circulation of a contaminated nutrient medium), there was no observable bacterial adhesion at the surface of the Cu exchanged material. These results confirm the antifouling properties of the Cu mordenite layer due to both the increased hydrophilicity and antibacterial properties of the active layer.Tests performed with tubular filtration membranes (without copper exchange) showed a significant decline in membrane hydraulic properties during filtration of culture media containing bacteria, whereas copper exchanged membranes showed no decline in hydraulic permeability. Filtration tests performed with concentrated culture media containing spores of B. subtilis led to a significant decrease in membrane hydraulic permeabilities (but less so with Cu exchanged membranes). The surfaces showed less effective global antifouling properties during the filtration of a concentrated culture medium due to competition between bacterial growth and the bactericidal effect of copper. Analyses of copper leached in solution show that after a conditioning step, the amount of copper released is negligible. PMID- 27680002 TI - Quality of urban runoff in wet and dry seasons: a case study in a semi-arid zone. AB - Urban runoff (UR) is a promising new resource that may alleviate growing tensions in numerous arid and semi-arid regions of the world. However, it is precisely in these zones that the available UR quality characteristics are scarcer. This work aims to evaluate a wide set of parameters to establish a detailed approach to both the quality of UR in a midsized city in Central Mexico and the feasibility of using UR to recharge aquifers. UR from an institutional land use site was sampled during wet and dry seasons and assessed for suspended solids, organic matter, nutrients, microorganisms, metals, and persistent organic chemicals (i.e., polycyclic aromatic hydrocarbons, PAH). The results were analyzed using multivariate statistical methods to identify relationships among the variables, the sampling sites and the seasons. The soil erosion and the leaching of materials due to the water flow through vegetated areas were identified as the most influencing factor on the quality of the site runoff in both dry and wet seasons. Additionally, data were more heterogeneous during the dry season, and higher pollutant concentrations were found both during the dry season and in more pervious zones. We consider UR a promising water source for recharging aquifers in arid and semi-arid zones if a program is implemented that can integrate an adequate runoff treatment system, soil protection, and other non-structural measures. PMID- 27680003 TI - Nutrient and toxic element soil concentrations during repeated mineral and compost fertilization treatments in a Mediterranean agricultural soil. AB - Agricultural soils of semi-arid Mediterranean areas are often subjected to depletion of their chemical, physical, and biological properties. In this context, organic fertilization, in addition to providing nutrients for a longer time in respect to mineral fertilization, improves many other characteristics related to soil fertility. Moreover, the combined use of organic and mineral fertilizers may promote a more sustainable crop production. However, a concern on the long-term use of organic fertilizers arises in relation to the possible accumulation of toxic elements in soil and their transfer to human beings. For this reason, a long-term study on nutrient and toxic element total concentrations and availabilities during fertilization treatments was carried out. In particular, mineral NPK fertilized soils, soils amended with biowaste compost, soils amended with biowaste compost plus mineral nitrogen, and unfertilized soils were analyzed for 11 chemical elements. The results highlighted that temporal variations in total and bioavailable concentrations of both nutrients and toxic elements, occurring also in unfertilized soils, are wider than those related to fertilization treatments. Anyway, soil amendments with biowaste compost, alone or in combination with mineral fertilizers, reduce Cu bioavailability but improve K, Fe, Mn, and Zn availabilities, excluding at the same time a long-term accumulation in soil. Total and bioavailable toxic element concentrations (apart from available Cd) do not vary in relation to fertilization treatments. PMID- 27680004 TI - Wastewater reuse: modeling chloroform formation. AB - The chloroform is a substance that presents a significant risk to or via the aquatic environment. Thus, the emissions, discharges and losses of this substance need to be controlled during wastewater disinfection for reclamation and reuse purposes. Due to its carcinogenetic potential, multiple studies have been carried out on drinking and surface/natural waters but less consideration has been directed to the wastewater disinfection. The focus of this work studied the formation of chloroform during chlorination in prepared waters or artificial matrices that intended to simulate wastewaters stored in landscape ponds for green areas irrigation. The relation between reaction time, chlorine dose, and chloroform formation and the variation of the dissolved organic carbon (DOC) content during the reaction was assessed. A two-variant model was proposed to simulate breakpoint chlorination practices (when chlorine dose is equal or lower than chlorine demand) and super chlorination techniques (when chlorine dose tends to surpass chlorine demand). The model was validated by the application of actual data from working conditions of six wastewater treatment plants located in Algarve, Portugal, including other data obtained in previous research studies that were not used in the model development, and by comparing the predicted values with real measured ones. PMID- 27680005 TI - Health implications of atmospheric aerosols from asbestos-bearing road pavements traditionally used in Southern Brazil. AB - Serpentine and amphibole asbestos occur naturally in certain geologic settings worldwide, most commonly in association with ultramafic rocks, along associated faults. Ultramafic rocks have been used in Pien County, Southern Brazil for decades for the purpose of road paving in rural and urban areas, but without the awareness of their adverse environmental and health impact. The aim of this study was the chemical characterization of aerosols re-suspended in two rural roads of Pien, paved with ultramafic rocks and to estimate the pulmonary deposition of asbestos aerosols. Bulk aerosol samples were analyzed by means of X-ray fluorescence spectrometry and X-ray diffraction analysis, in order to characterize elemental composition and crystallinity. Single-particle compositions of aerosols were analyzed by computer-controlled electron-probe microanalysis, indicating the presence of a few percentages of serpentine and amphibole. Given the chemical composition and size distribution of aerosol particles, the deposition efficiency of chrysotile, a sub-group of serpentine, in two principal segments of the human respiratory system was estimated using a lung deposition model. As an important finding, almost half of the inhaled particles were calculated to be deposited in the respiratory system. Asbestos depositions were significant (~25 %) in the lower airways, even though the selected breathing conditions (rest situation, nose breathing) implied the lowest rate of respiratory deposition. Considering the fraction of inhalable suspended chrysotile near local roads, and the long-term exposure of humans to these aerosols, chrysotile may represent a hazard, regarding more frequent development of lung cancer in the population of the exposed region. PMID- 27680006 TI - Hematological, biochemical, and toxicopathic effects of subchronic acetamiprid toxicity in Wistar rats. AB - Acetamiprid is one of the most widely used neonicotinoids. This study investigates toxic effects of repeated oral administration of three doses of acetamiprid (1/20, 1/10, and 1/5 of LD50) during 60 days. For this, male Wistar rats were divided into four different groups. Hematological, biochemical, and toxicopathic effects of acetamiprid were evaluated. According to the results, a significant decrease in the body weight gain at the highest dose 1/5 of LD50 of acetamiprid was noticed. An increase in the relative liver weight was also observed at this dose level. The hematological constituents were affected. A significant decrease in RBC, HGB, and HCT in rats treated with higher doses of acetamiprid (1/10 and 1/5 of LD50) was noted. However, a significant increase in WBC and PLT were observed at the same doses. Furthermore, acetamiprid induced liver toxicity measured by the increased activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphates (ALPs), and lactate dehydrogenase (LDH) which may be due to the loss of hepatic membrane architecture and hepatocellular damage. In addition, exposure to acetamiprid resulted in a significant decrease in the levels of superoxide dismutase and catalase activities (p <= 0.01) with concomitant increase in lipid peroxidation in rat liver. These findings highlight the subchronic hepatotoxicity of acetamiprid. PMID- 27680007 TI - Chemical assessment of lead, cadmium, nitrate, and nitrite intakes with daily diets of children and adolescents from orphanages in Krakow, Poland. AB - The aim of this study has been to measure the level of lead, cadmium, nitrates, and nitrites in the daily diets of children and adolescents from orphanages located in Krakow (Poland). Diets were collected over four seasons of 2009. The content of cadmium and lead was measured with flameless atomic absorption spectrometry. Nitrates and nitrites in diets were measured using the Griess colorimetric method. In all orphanages, the average intake of lead with daily diets, regardless of the season, ranged from 1.11 +/- 0.15 to 22.59 +/- 0.07 MUg/kg bw/week. The average cadmium intake by children and adolescents ranged between 3.09 +/- 0.21 and 20.36 +/- 2.21 MUg/kg bw/week and, for all orphanages, exceeded the tolerable weekly intake (TWI) level. Daily intake of nitrates and nitrites ranged respectively from 27 to 289 % and from 9 to 99 % of the acceptable daily intake (ADI). The youngest children, with lower body mass, were particularly sensitive to the excessive intakes of cadmium and nitrates. PMID- 27680008 TI - Detection of human fecal contamination by nifH gene quantification of marine waters in the coastal beaches of Rio de Janeiro, Brazil. AB - The identification of fecal pollution in aquatic ecosystems is one of the requirements to assess the possible risks to human health. In this report, physicochemical parameters, Escherichia coli enumeration and Methanobrevibacter smithii nifH gene quantification were conducted at 13 marine waters in the coastal beaches of Rio de Janeiro, Brazil. The pH, turbidity, dissolved oxygen, temperature, and conductivity, carried out by mobile equipment, revealed varied levels due to specific conditions of the beaches. The bioindicators' enumerations were done by defined substrate method, conventional, and real-time PCR. Six marine beach sites (46 %) presenting E. coli levels in compliance with Brazilian water quality guidelines (<2500 MPN/100 mL) showed nifH gene between 5.7 * 109 to 9.5 * 1011 copies. L-1 revealing poor correlation between the two approaches. To our knowledge, this is the first inquiry in qPCR using nifH gene as a biomarker of human-specific sources of sewage pollution in marine waters in Brazil. In addition, our data suggests that alternative indicator nifH gene could be used, in combination with other markers, for source tracking studies to measure the quality of marine ecosystems thereby contributing to improved microbial risk assessment. PMID- 27680009 TI - [Cutaneous squamous cell carcinoma]. AB - Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. A risk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients. PMID- 27680010 TI - [Skin cancer as occupational disease]. AB - The incidence of epithelial skin neoplasms, such as squamous cell carcinoma and basal cell carcinoma is significantly increasing worldwide. Leisure time solar UV exposure is causative in the overwhelming majority of cases in the general population; however, occupational exposure is responsible for a certain percentage of cases. Employees with a relevant exposure to polycyclic aromatic hydrocarbons in soot, raw paraffin, coal tar, anthracene, pitch or similar substances, to sunlight in outdoor occupations as well as to arsenic and ionizing radiation have a significantly increased risk to develop occupational skin cancer compared to the general population. In the official occupational disease list in the appendix of the German by-law on occupational diseases, the following occupational diseases concerning skin cancer are listed: BK 5102 "skin cancer and carcinoma in situ caused by soot, raw paraffin, coal tar, anthracene, pitch or similar substances" (e.g. various solid paraffins, asphalt and mazut as well as mineral oils, grease, cylinder and drilling oils), BK 5103 "squamous cell carcinoma or multiple actinic keratosis caused by natural UV radiation", BK 1108 "diseases caused by arsenic and its compounds" and BK 2402 "diseases caused by ionizing radiation". For further occupational exposure to carcinogenic substances and potential occupationally acquired skin tumors, no official lists are currently available. These cancers might be considered under a special opt out paragraph in the German Social Law (S 9 para 2 SGB VII). Tumors in scars after occupational skin trauma or occupational burns are compensated as consequences of work accidents. The current official list of occupational skin cancers and new developments for expert opinions are described in this article. PMID- 27680011 TI - [Wound management with enzyme alginogels : Expert consensus]. AB - BACKGROUND: The challenges of modern wound management, such as the treatment of chronic wounds and their phase-specific handling, are demanding and require optimally adapted therapeutic measures. The principles of moist wound care as well as an adequate debridement have priority here. To support these necessary measures, different options are available, e.g., a new product group operating across several wound phases. OBJECTIVE: A new treatment principle in modern wound management based on an expert consensus is presented. METHODS: On the basis of clinical experience reports and published evidence, the current and new principles of wound treatment were discussed in a panel of experts and formulated as a consensus statement. RESULTS: Enzyme alginogels represent a combination of agents that allow phase-specific wound care. They exhibit autolytic, absorbent, and antimicrobial properties and simultaneously cover three components of wound management based on the TIME framework. Thus, according to the experts, they differ from other wound healing products and can be classified in a distinct product group. Clinical studies, as well as clinical experiences, provide evidence for the efficacy of enzyme alginogels. DISCUSSION: According to the experts, the potential of enzyme alginogels used considering the principles of moist wound care, comprises the three-fold effect (continuous and significantly simplified debridement, maintaining a moist wound environment and antimicrobial effect without cytotoxicity), the ease of use, and the flexible application. In addition, the flexibility of the product class regarding frequency of application, duration of treatment and combinability with secondary dressings, are of economic benefit in the health care sector. PMID- 27680012 TI - Abnormal serum microRNA profiles in tuberous sclerosis are normalized during treatment with everolimus: possible clinical implications. AB - BACKGROUND: Tuberous sclerosis (TSC) is a monogenic disease resulting from defects of the TSC1 or TSC2 genes, which encode the proteins forming hamartin tuberin tumor suppressor complex, the mammalian target of rapamycin complex (mTOR). The mTOR pathway is constitutively activated in response to tuberin or hamartin defects. The mTOR pathway is also regulated by a multitude of epigenetic mechanisms, one of which is regulation by microRNA (miRNA) inhibition. This leads us to hypothesize that organ-level abnormalities of miRNA expression patterns are widespread in TSC. The aim of the study was to evaluate the serum profiles of miRNAs in patients with TSC and subependymal giant cell astrocytoma (SEGA) treated with mTOR inhibitor (everolimus). METHODS: Serum microRNA profiling was performed in 10 TSC-patients before and three months after everolimus treatment, as well as in 10 sex- and age-matched healthy controls. MicroRNAs were profiled using qPCR panels (Exiqon). RESULTS: Of 752 tested miRNAs, 11 showed statistically significant dysregulation in patients with TSC in comparison to controls. The following miRNAs were downregulated in TSC: miR-142-3p, miR-199a 5p, miR-142-5p and miR-136-5p; while miR-130a-3p, miR-378a-3p, miR-130b-3p, miR 192-5p, miR-25-3p, miR-215-5p and miR-222-3p were upregulated in TSC in comparison to the control group. After three months of everolimus treatment, mean dose 5.1 (2.6-9.7) mg/m2, seven miRNAs reached expression levels similar to healthy controls, with miR-142-3p and miR-136 showed significant increase over baseline levels in TSC patients. Moreover, miR-222-3p normalization due to treatment differed between patients with mutation in TSC1 and TSC2 gene. CONCLUSIONS: Activation of the mTOR pathway in TSC patients alters serum miRNA levels, which may be partially reversed by an mTOR inhibitor. This indicates the involvement of miRNA dysregulation in the pathogenesis of TSC, linking miRNA profiles with treatment efficiency. PMID- 27680014 TI - Comparison of MRI- and CT-based semiautomated liver segmentation: a validation study. AB - PURPOSE: To compare the repeatability, agreement, and efficiency of MRI- and CT based semiautomated liver segmentation for the assessment of total and subsegmental liver volume. METHODS: This retrospective study was conducted in 31 subjects who underwent contemporaneous liver MRI and CT. Total and subsegmental liver volumes were segmented from contrast-enhanced 3D gradient-recalled echo MRI sequences and CT images. Semiautomated segmentation was based on variational interpolation and Laplacian mesh optimization. All segmentations were repeated after 2 weeks. Manual segmentation of CT images using an active contour tool was used as the reference standard. Repeatability and agreement of the methods were evaluated with intra-class correlation coefficients (ICC) and Bland-Altman analysis. Total interaction time was recorded. RESULTS: Intra-reader ICC were >=0.987 for MRI and >=0.995 for CT. Intra-reader repeatability was 30 +/- 217 ml (bias +/- 1.96 SD) (95% limits of agreement: -187 to 247 ml) for MRI and -10 +/- 143 ml (-153 to 133 ml) for CT. Inter-method ICC between semiautomated and manual volumetry were >=0.995 for MRI and >=0.986 for CT. Inter-method segmental ICC varied between 0.584 and 0.865 for MRI and between 0.596 and 0.890 for CT. Inter method agreement was -14 +/- 136 ml (-150 to 122 ml) for MRI and 50 +/- 226 ml ( 176 to 276 ml) for CT. Inter-method segmental agreement ranged from 10 +/- 47 ml (-37 to 57 ml) to 2 +/- 214 ml (-212 to 216 ml) for MRI and 9 +/- 45 ml (-36 to 54 ml) to -46 +/- 183 ml (-229 to 137 ml) for CT. Interaction time (mean +/- SD) was significantly shorter for MRI-based semiautomated segmentation (7.2 +/- 0.1 min, p < 0.001) and for CT-based semiautomated segmentation (6.5 +/- 0.2 min, p < 0.001) than for CT-based manual segmentation (14.5 +/- 0.4 min). CONCLUSION: MRI based semiautomated segmentation provides similar repeatability and agreement to CT-based segmentation for total liver volume. PMID- 27680013 TI - Reduced-fluence verteporfin photodynamic therapy plus ranibizumab for choroidal neovascularization in pathologic myopia. AB - BACKGROUND: To demonstrate the efficacy of intravitreal ranibizumab (IVR) in combination with reduced-fluence photodynamic therapy (RF-PDT) in patients with choroidal neovascularization (CNV) secondary to pathologic myopia. METHODS: Sixty patients affected by myopic CNV (mCNV) were randomized to receive either ranibizumab 0.5 mg monotherapy (RM; n = 20), standard fluence PDT (SF-PDT, n = 20) or RF-PDT combination therapy (n = 20). Subsequently, IVR was injected as needed. All patients were evaluated for 48 weeks. RESULTS: Mean BCVA change at 48 weeks was + 0.2 and +15 letters with SF or RFPDT plus ranibizumab, respectively, compared with +16.8 letters with RM. At 48 weeks, mean central foveal thickness (CFT) decrease from baseline was 58 +/- 15 MUm, 91.4 +/- 43.8 MUm, and 85 +/- 41.5 MUm for the verteporfin SF, RF and RM groups, respectively. Macular sensitivity improvement was + 0.4 db, + 1.9 dB and + 2.7 dB for the verteporfin SF, RF and RM groups, respectively. CONCLUSIONS: Ranibizumab monotherapy or combined with RF-PDT improved BCVA and macular sensitivity in patients affected by mCNV, whereas CFT results were reduced. SF-PDT combination regimen mostly stabilized vision at 48 weeks. Among all groups, the RF-PDT seemed to reduce the number of ranibizumab retreatments. PMID- 27680015 TI - Practical use and pitfalls of hepatocyte-specific contrast agents (HSCAs) for pediatric hepatic and biliary magnetic resonance imaging. AB - Magnetic resonance imaging is commonly used to evaluate for hepatic and biliary pathology in the pediatric population. Recently, there has been increased use of hepatocyte-specific contrast agents (HSCAs), such as Gadoxetate disodium in children. Traditionally, HSCAs have been used to characterize focal liver lesions. However, these agents can also be used to problem solve specific hepatic or biliary diagnostic dilemmas. The purpose of this manuscript is to review the practical uses of HSCA in children with both hepatic and biliary indications, and review the corresponding imaging findings. We will highlight the diagnostic uses of HSCA in children, as well as pitfalls encountered. PMID- 27680017 TI - Should low-income countries invest in breast cancer screening? AB - With the increase in incidence and mortality of breast cancer in low-income countries (LICs), the question of whether LICs should promote breast cancer screening for early detection has gained tremendous importance. Because LICs have limited financial resources, the value of screening must be carefully considered before integrating screening programs into national healthcare system. Mammography-the most commonly used screening tool in developed countries-reduces breast cancer-specific mortality among women of age group 50-69, but the evidence is not so clear for younger women. Further, it does not reduce the overall mortality. Because the women in LICs tend to get breast cancer at younger age and are faced with various competing causes of mortality, LICs need to seriously evaluate whether mammographic screening presents a good value for the investment. Instead, we suggest a special module of clinical breast examination that could provide similar benefits at a very low cost. Nevertheless, we believe that LICs would obtain a much greater value for their investment if they promote primary prevention by tobacco cessation, healthier food and healthier lifestyle campaigns instead. PMID- 27680016 TI - Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women's Health Across the Nation. AB - PURPOSE: Two case-control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer. METHODS: We evaluated this relationship in the longitudinal Study of Women's Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment. RESULTS: Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77). CONCLUSION: VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship. PMID- 27680018 TI - Endocrine therapy and urogenital outcomes among women with a breast cancer diagnosis. AB - PURPOSE: Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers. METHODS: Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort. Tumor characteristics and endocrine therapy use were collected from medical and prescription records. We calculated multivariable prevalence ratios (PR) and 95 % confidence intervals (CI) for the association of endocrine therapy (versus no endocrine therapy) and urinary incontinence, overall and by therapy type (tamoxifen or aromatase inhibitors). PROMIS Sexual Function and Satisfaction domain scores were compared across endocrine therapy groups. RESULTS: Among the 548 women with a breast cancer diagnosis, 49 % received endocrine therapy. Overall, 18 % of women reported urinary incontinence symptoms. We observed no association between urinary incontinence and endocrine therapy use overall (PR = 0.97; 95 % CI 0.67, 1.43), tamoxifen (PR = 1.20; 95 % CI 0.74, 1.96), or aromatase inhibitors (PR = 0.89; 95 % CI 0.55, 1.42), compared to no use. Approximately 55 % of women were sexually active. Sexual function scores did not vary according to endocrine therapy use, although urinary incontinence was associated with lower satisfaction scores (p = 0.05). CONCLUSIONS: Our findings demonstrate a high prevalence of urinary incontinence after breast cancer diagnosis similar to the overall prevalence in older U.S. women, and this did not vary strongly according to use of endocrine therapy. PMID- 27680019 TI - Striking Phenotypic Variation yet Low Genetic Differentiation in Sympatric Lake Trout (Salvelinus namaycush). AB - The study of population differentiation in the context of ecological speciation is commonly assessed using populations with obvious discreteness. Fewer studies have examined diversifying populations with occasional adaptive variation and minor reproductive isolation, so factors impeding or facilitating the progress of early stage differentiation are less understood. We detected non-random genetic structuring in lake trout (Salvelinus namaycush) inhabiting a large, pristine, postglacial lake (Mistassini Lake, Canada), with up to five discernible genetic clusters having distinctions in body shape, size, colouration and head shape. However, genetic differentiation was low (FST = 0.017) and genetic clustering was largely incongruent between several population- and individual-based clustering approaches. Genotype- and phenotype-environment associations with spatial habitat, depth and fish community structure (competitors and prey) were either inconsistent or weak. Striking morphological variation was often more continuous within than among defined genetic clusters. Low genetic differentiation was a consequence of relatively high contemporary gene flow despite large effective population sizes, not migration-drift disequilibrium. Our results suggest a highly plastic propensity for occupying multiple habitat niches in lake trout and a low cost of morphological plasticity, which may constrain the speed and extent of adaptive divergence. We discuss how factors relating to niche conservatism in this species may also influence how plasticity affects adaptive divergence, even where ample ecological opportunity apparently exists. PMID- 27680021 TI - MR-guided attenuation map for prostate PET-MRI: an intensity and morphologic based segmentation approach for generating a five-class attenuation map in pelvic region. AB - PURPOSE: Prostate imaging is one of the major application of hybrid PET/MRI systems. Inaccurate attenuation maps (u-maps) derived by direct segmentation (SEG) in which the cortical bone is ignored and the volume of the air in cavities is underestimated is the main challenge of commercial PET/MRI systems for the quantitative analysis of the pelvic region. The present study considered the cortical bone and air cavity along with soft tissue, fat, and background air in the u-map of the pelvic region using a method based on SEG. The proposed method uses a dedicated imaging technique that increases the contrast between regions and a hybrid segmentation method to classify MR images based on intensity and morphologic characteristics of tissues, such as symmetry and similarity of bony structures. PROCEDURES: Ten healthy volunteers underwent MRI and ultra-low dose CT imaging. The dedicated MR imaging technique uses the short echo time (STE) based on the conventional sequencing implemented on a clinical 1.5T MRI scanner. The generation of a u-map comprises the following steps: (1) bias field correction; (2) hybrid segmentation (HSEG), including segmenting images into clusters of cortical bone-air, soft tissue, and fat using spatial fuzzy c-means (SFCM), and separation of cortical bone and internal air cavities using morphologic characteristics; (3) the active contour approach for the separation of background air; and (4) the generation of a five-class MU-map for cortical bone, internal air cavity, soft tissue, fat tissue, and background air. Validation was done by comparison with segmented CT images. RESULTS: The Dice and sensitivity metrics of cortical bone structures and internal air cavities were 72 +/- 11 and 66 +/- 13 and 73 +/- 10 and 68 +/- 20 %, respectively. High correlation was observed between CT and HSEG-based u-maps (R 2 > 0.99) and the corresponding sinograms (R 2 > 0.98). CONCLUSIONS: Currently, pelvis u-maps provided by the current PET/MRI systems and the ultra-short echo time and atlas based methods tend to be inaccurate. The proposed method acceptably generated a five-class MU-map using only one image. PMID- 27680022 TI - Synthesis and basic evaluation of 7alpha-(3-[18F]fluoropropyl)-testosterone and 7alpha-(3-[18F]fluoropropyl)-dihydrotestosterone. AB - OBJECTIVE: 7alpha-Substituted androgen derivatives may have the potential to visualize androgen receptors with positron emission tomography. In the present study, we synthesized fluoropropyl derivatives of 7alpha-(3-[18F]fluoropropyl) testosterone ([18F]7) and 7alpha-(3-[18F]fluoropropyl)-dihydrotestosterone ([18F]15), and characterized their in vitro binding, in vivo biodistribution, and performed blocking studies in mature androgen deprived male rats. METHODS: We synthesized [18F]7 and [18F]15. In vitro binding to recombinant rat AR ligand binding domain protein was determined using a competitive radiometric ligand binding assay with the high-affinity synthetic androgen [17alpha-methyl-3H] methyltrienolone ([3H]R1881). In vivo biodistribution was performed in mature male rats treated with diethylstilbestrol (chemical castration). A blocking study was performed by co-administration of dihydrotestosterone (36 ug/animal). RESULTS: 7alpha-(3-Fluoropropyl)-testosterone (7) and 7alpha-(3-fluoropropyl) dihydrotestosterone (15) showed competitive binding to recombinant rat AR ligand binding domain protein. The IC50 value of 15 (13.0 +/- 3.3 nM) was higher than 7 (47.8 +/- 10.0 nM). In contrast to the AR binding affinity, the ventral prostate uptake of [18F]7 and [18F]15 at 2 h post-injection was similar (0.07 % injected dose/g of tissue). A blocking study indicated that specific binding of [18F]15 is observed in the ventral prostate. [18F]7 and [18F]15 showed moderate levels of bone uptake, which indicates moderate metabolic de-fluorination in rodents. CONCLUSION: [18F]15 is better than [18F]7 in terms of radiochemical yield, in vitro binding affinity, prostate specific binding and stability against in vivo metabolic de-fluorination. However, the net uptake level of [18F]15 in prostate might be insufficient for in vivo visualization. Although [18F]7 and [18F]15 improved in vivo stability against de-fluorination, other basic characterization data in rodents were not superior to the current standard tracer 16beta [18F]fluoro-5alpha-dihydrotestosterone. It is also revealed that the shorter side chain length of 7alpha-[18F]fluoromethyl-dihydrotestosterone is superior to the longer three carbon chain in [18F]15, in terms of net prostate uptake and in vivo metabolic stability. PMID- 27680025 TI - BMA invites health secretary to symposium on seven day services. PMID- 27680023 TI - Clinical Application of a Hybrid RapidArc Radiotherapy Technique for Locally Advanced Lung Cancer. AB - OBJECTIVE: Radiation treatment planning for locally advanced lung cancer can be technically challenging, as delivery of >=60 Gy to large volumes with concurrent chemotherapy is often associated with significant risk of normal tissue toxicity. We clinically implemented a novel hybrid RapidArc technique in patients with lung cancer and compared these plans with 3-dimensional conformal radiotherapy and RapidArc-only plans. MATERIALS/METHODS: Hybrid RapidArc was used to treat 11 patients with locally advanced lung cancer having bulky mediastinal adenopathy. All 11 patients received concurrent chemotherapy. All underwent a 4-dimensional computed tomography planning scan. Hybrid RapidArc plans concurrently combined static (60%) and RapidArc (40%) beams. All cases were replanned using 3- to 5 field 3-dimensional conformal radiotherapy and RapidArc technique as controls. RESULTS: Significant reductions in dose were observed in hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans for total lung V20 and mean (-2% and -0.6 Gy); contralateral lung mean (-2.92 Gy); and esophagus V60 and mean (-16.0% and -2.2 Gy; all P < .05). Contralateral lung doses were significantly lower for hybrid RapidArc plans compared to RapidArc-only plans (all P < .05). Compared to 3-dimensional conformal radiotherapy, heart V60 and mean dose were significantly improved with hybrid RapidArc (3% vs 5%, P = .04 and 16.32 Gy vs 16.65 Gy, P = .03). However, heart V40 and V45 and maximum spinal cord dose were significantly lower with RapidArc plans compared to hybrid RapidArc plans. Conformity and homogeneity were significantly better with hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans ( P < .05). Treatment was well tolerated, with no grade 3+ toxicities. CONCLUSION: To our knowledge, this is the first report on the clinical application of hybrid RapidArc in patients with locally advanced lung cancer. Hybrid RapidArc permitted safe delivery of 60 to 66 Gy to large lung tumors with concurrent chemotherapy and demonstrated advantages for reduction in low-dose lung volumes, esophageal dose, and mean heart dose. PMID- 27680027 TI - Association of Periodontal Destruction and Diabetes with Mortality. AB - Current evidence indicates the effects of periodontitis on diabetes as well as mortality, for which diabetes itself represents a risk factor. However, the possible interaction of these 2 chronic conditions regarding mortality has not yet been investigated. Therefore, the purpose of this study was to evaluate whether periodontal destruction interacts with diabetes on all-cause and cardiovascular disease (CVD) mortality or if diabetes serves as a mediator in this association. The study sample comprised 3,327 participants aged 20 to 81 y from the Study of Health in Pomerania. Periodontal destruction was assessed via clinical attachment level (CAL) and the number of missing teeth. Information on mortality (date and ICD-10 code) was ascertained from death certificates. Directed acyclic graphs were used to identify potential confounders, and Cox proportional hazard models were applied. In 36,701 person-years of follow-up, 263 study participants deceased, 89 due to CVD. Fully adjusted main effect models resulted in hazard ratios of 1.01 (95% confidence interval [95% CI]: 1.002 to 1.01) for extent of CAL >=3 mm, 1.10 (95% CI: 1.03 to 1.18) for mean CAL, and 1.03 (95% CI: 1.01 to 1.04) for the number of missing teeth regarding all-cause mortality. Analogous results were obtained for CVD mortality, with hazard ratios of 1.01 (95% CI: 0.99 to 1.02), 1.10 (95% CI: 0.98 to 1.23), and 1.02 (95% CI: 0.99 to 1.05) for extent of CAL, mean CAL, and the number of missing teeth, respectively. Findings did not indicate additive interaction of periodontal destruction and diabetes regarding all-cause and CVD mortality. Similarly, no substantial evidence was found to demonstrate the presence of multiplicative interaction or mediation. Besides adjustment for baseline covariates, time varying covariates were also considered and led to comparable results. In summary, despite their reciprocal relationship, periodontal destruction and diabetes may be independent risk factors for all-cause and CVD mortality. PMID- 27680024 TI - Expression Pattern of Axin2 During Chicken Development. AB - Canonical Wnt-signalling is well understood and has been extensively described in many developmental processes. The regulation of this signalling pathway is of outstanding relevance for proper development of the vertebrate and invertebrate embryo. Axin2 provides a negative-feedback-loop in the canonical Wnt-pathway, being a target gene and a negative regulator. Here we provide a detailed analysis of the expression pattern in the development of the chicken embryo. By performing in-situ hybridization on chicken embryos from stage HH 04+ to HH 32 we detected a temporally and spatially restricted dynamic expression of Axin2. In particular, data about the expression of Axin2 mRNA in early embryogenesis, somites, neural tube, limbs, kidney and eyes was obtained. PMID- 27680028 TI - Prevalence and Mechanisms of Peri-implant Diseases. AB - The aim of the present critical review is to summarize recent evidence on the prevalence of peri-implant diseases and their similarities and differences with periodontal diseases with a focus on their pathogenetic mechanisms. Reports on the extent and severity of peri-implant diseases are influenced by different case definitions. The prevalence of peri-implant diseases is reported at the subject or implant level and affected by the type of population samples analyzed (e.g., randomly selected population samples or convenience samples). The outcomes of studies on animals and humans indicate that experimental biofilm accumulation leads to a higher frequency of bleeding sites around implants as compared with teeth. Despite the proof of principle that experimentally induced mucositis may be reversible, early diagnosis and management of naturally occurring peri-implant mucositis are clinically relevant. Tissue destruction at experimental peri implantitis sites is faster and more extensive when compared with that at experimental periodontitis sites. Although human periodontitis and peri implantitis lesions share similarities with respect to etiology and clinical features, they represent distinct entities from a histopathologic point of view. To avoid implant loss, patients diagnosed with peri-implantitis should be treated without delay. PMID- 27680026 TI - Kinase Regulation of Human MHC Class I Molecule Expression on Cancer Cells. AB - The major histocompatibility complex I (MHC-1) presents antigenic peptides to tumor-specific CD8+ T cells. The regulation of MHC-I by kinases is largely unstudied, even though many patients with cancer are receiving therapeutic kinase inhibitors. Regulators of cell-surface HLA amounts were discovered using a pooled human kinome shRNA interference-based approach. Hits scoring highly were subsequently validated by additional RNAi and pharmacologic inhibitors. MAP2K1 (MEK), EGFR, and RET were validated as negative regulators of MHC-I expression and antigen presentation machinery in multiple cancer types, acting through an ERK output-dependent mechanism; the pathways responsible for increased MHC-I upon kinase inhibition were mapped. Activated MAPK signaling in mouse tumors in vivo suppressed components of MHC-I and the antigen presentation machinery. Pharmacologic inhibition of MAPK signaling also led to improved peptide/MHC target recognition and killing by T cells and TCR-mimic antibodies. Druggable kinases may thus serve as immediately applicable targets for modulating immunotherapy for many diseases. Cancer Immunol Res; 4(11); 936-47. (c)2016 AACR. PMID- 27680030 TI - Gonadal function in boys with newly diagnosed cancer before the start of treatment. AB - STUDY QUESTION: Are Inhibin B and testosterone levels reduced in boys with newly diagnosed cancer prior to therapy? SUMMARY ANSWER: Pretreatment serum levels of Inhibin B and testosterone are significantly reduced in boys with newly diagnosed cancer, compared to reference values. WHAT IS ALREADY KNOWN: Disease-related gonadal impairment has been demonstrated in girls and young women diagnosed with cancer, prior to therapy. STUDY DESIGN, SIZE, DURATION: We conducted a descriptive study in boys newly diagnosed with cancer between January 2006 and February 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum Inhibin B and testosterone levels were determined in 224 boys, up to the age of 18 years, with newly diagnosed cancer prior to therapy. Hormone levels were compared with age matched reference values. The cohort consisted of patients with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma (HL), non-Hodgkin lym-phoma (NHL), nephroblastoma, neuroblastoma and sarcoma. MAIN RESULTS AND THE ROLE OF CHANCE: This study demonstrates reduced serum levels of Inhibin B in boys with newly diagnosed cancer, compared to reference values (standard deviation score (SDS) -0.9, P < 0.001). Median Inhibin B level in patients was 103.5 ng/l (range 20-422). Of all patients, 78.6% showed Inhibin B levels below the 50th percentile, and 58.5% had Inhibin B levels below the 25th percentile. Serum testosterone levels were significantly lower than the reference range population (SDS -1.2, P < 0.001). Median testosterone level in pubertal patients was 7.3 nmol/l (range 0.1-23.6). No correlation with clinical signs of general illness and hormone levels were observed. LIMITATIONS, REASONS FOR CAUTION: In this study, reproductive hormone levels were compared with age matched reference values. Future studies may compare reproductive hormone levels with case controls. WIDER IMPLICATIONS OF THE FINDINGS: Future longitudinal studies are necessary to determine whether pretreatment impaired gonadal function at the time of cancer diagnosis is an important determinant of ultimate recovery of spermatogenesis after treatment and later on in adulthood. STUDY FUNDING/COMPETING INTERESTS: W.v.D. was supported by the Pediatric Oncology Center Society for Research (KOCR), Rotterdam, The Netherlands. A.-L.L.F.v.d.K. was supported by EU FP7 PanCare LIFE study. The authors have no conflicts of interest. PMID- 27680032 TI - Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells. AB - Adequate revascularization is a prerequisite for successful healing of periodontal bone defects. This study characterized three different xenogeneic bone grafting materials: Gen-Os of equine and porcine origins, and anorganic Bio Oss. We also investigated their angiogenic potential. All materials were composed of poorly crystalline calcium oxide phosphate, with Bio-Oss exhibiting a carbonated phase and larger particle size and both Gen-Os showing the presence of collagen. Both Gen-Os materials significantly enhanced vascular endothelial growth factor (VEGF) secretion by PDL cells. A significant increase in endothelial cell proliferation was observed in cultures with both Gen-Os conditioned media, but not with that of Bio-Oss. Finally, angiogenesis was stimulated by both Gen-Os conditioned media as demonstrated by an increased formation of capillary-like structures. Taken together, these findings indicate an enhanced angiogenic potential of both Gen-Os bone grafting materials when applied on PDL cells, most likely by increasing VEGF production. PMID- 27680029 TI - Intrauterine administration of hCG immediately after oocyte retrieval and the outcome of ICSI: a randomized controlled trial. AB - STUDY QUESTION: Does the intrauterine administration of hCG immediately after oocyte retrieval in antagonist cycles with ICSI and fresh embryo transfer (ET) influence the implantation rate or chemical and clinical pregnancy rates? SUMMARY ANSWER: The intrauterine administration of hCG after oocyte retrieval increases the implantation rate and chemical and clinical pregnancy rates. WHAT IS KNOWN ALREADY: Over half of IVF/ICSI cycles fail due to implantation failure. Intrauterine administration of hCG, a few minutes before ET, increased the implantation and pregnancy rates in most but not in all studies. The effect of intrauterine administration of hCG, after oocyte retrieval, has not yet been studied. STUDY DESIGN, SIZE, DURATION: The study was a parallel, triple-blind randomized clinical trial (RCT) performed from September 2015 to February 2016, in a university hospital. We recruited women undergoing antagonist ovarian stimulation, ICSI and ET. For an effect size of 0.2, power of 80% at a significance level of 0.05, we needed 150 participants. Accounting for a 7% dropout rate, a total of 160 women was considered appropriate. A computer generated randomization list with a block size of 4, with 1:1 allocation was used. The treatment allocation was placed in a sealed, opaque, envelope and picked up consecutively. Immediately after oocyte retrieval, patients in the intervention and control groups were treated with intrauterine injection of hCG and saline, respectively. Participants underwent ET on Day 3. A beta-hCG test was done at 2 weeks. If positive, three transvaginal-ultrasonographies (TVSs) were done at 3, 4 and 10 weeks after ET. The participants were called up thereafter and questioned about the continuity of their pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHOD: Of 1990 women attending the infertility clinic of our university hospital, 508 were IVF/ICSI candidates during the study period, and 245 of the patients on an antagonist cycle met the criteria to be invited into our trial. Inclusion criteria were normal ovarian reserve, age <=41, undergoing ICSI, and fresh ET and normal TSH and prolactin. Uncontrolled chronic disease, severe hydrosalpinx, severe endometriosis, morphologic embryo deficiencies, non obstructive azospermia and high risk of severe ovarian hyperstimulation syndrome were criteria for exclusion. After taking an informed consent, a total of 158 participants were recruited, of which 80 were randomly allocated to receive intrauterine 500 IU hCG in up to 0.5 ml normal saline and 78 to receive intrauterine 0.5 ml normal saline immediately after oocyte retrieval, during general anaesthesia. ICSI was performed conventionally. The 4-8 cell embryos were transferred on the third day after oocyte retrieval. Implantation rate, chemical and clinical pregnancy rates were analysed and compared between the two groups. MAIN RESULTS AND THE ROLE OF CHANCE: Patients' demographic and baseline characteristics were comparable. The clinical results showed statistically significant differences between the two groups regarding the biochemical pregnancy rate (59.2 versus 31.3%; P = 0.001; odds ratio (OR) = 1.88; 95% CI, 1.26-2.82; risk difference (RD) = 27.8; 95% CI, 11.2-42.3), implantation rate (37 versus 17%; P = 0.012; OR = 2.29; 95% CI, 1.02-5.14; RD = 20.2; 95% CI, 5.4 33.8), clinical pregnancy rate (50.7 versus 16.4%; P < 0.001; OR = 3.08; 95% CI, 1.71-5.55; RD = 34.3; 95% CI, 18.7-47.6) and ongoing pregnancy rate (40.1 versus 13.4%; P = 0.001; OR = 3.04; 95% CI, 1.55-5.93; RD = 27.4; 95% CI, 12.7-40.6). The abortion and ectopic pregnancy rates were not statistically different between the two groups. LIMITATIONS, REASONS FOR CAUTION: The insertion of an intrauterine insemination catheter and the injection of a small amount of saline into the uterine cavity (without hCG) may also have some impact on implantation. This effect could be studied by comparing this intervention with another study group without any intrauterine injection.There are no specific side effects mentioned in the literature for the intrauterine administration of hCG, neither were any observed in our study, but it is best to be cautious about probable side effects, because this type of intervention is relatively new and experimental, and deserves more studies before being entered into routine clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine administration of hCG immediately after oocyte pick up increases its effectiveness; however, further investigations are required before this procedure can be recommended for clinical practice. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Women's Health Research Center, Tabriz University of Medical Sciences, Iran. No external funds were used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: IRCT201206165485N4. TRIAL REGISTRATION DATE: 2 September 2015. DATE OF FIRST PATIENT'S ENROLMENT: 2 September 2015. PMID- 27680031 TI - Management of infections in rheumatic patients receiving biological therapies. The Portuguese Society of Rheumatology recommendations. AB - INTRODUCTION: Infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic diseases and the management of infectious complications in patients under biological therapies deserves particular attention. OBJECTIVE: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies. METHODS: A search in PubMed (until 10 November 2014) and EMBASE (until 20 December 2014) databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedicated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey. RESULTS: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the management of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections. CONCLUSION: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists. PMID- 27680034 TI - Development and modification of a device for three-dimensional measurement of orthodontic force system: The V-bend system re-visited. AB - We developed a device to evaluate the orthodontic force applied by systems requiring high operability. A life-sized, two-tooth model was designed, and the measurements were performed using a custom-made jointed attachment, referred to as an "action stick", to allow clearance for the oversized six-axis sensors. This tooth-sensor apparatus was accurately calibrated, and the error was limited. Vector analysis and rotating coordinate transformation were required to derive the force and moment at the tooth from the sensor readings. The device was then used to obtain measurements of the force and moment generated by the V-bend system. Our device was effective, providing results that were consistent with those of previous studies. This measurement device can be manufactured with force sensors of any size, and it can also be expanded to models with any number of teeth. PMID- 27680033 TI - Shear bond strength of a novel light cured calcium silicate based-cement to resin composite using different adhesive systems. AB - The shear bond strength (SBS) of TheraCal LC to resin composite was evaluated in comparison to Mineral trioxide aggregate (ProRoot MTA) and conventional glass ionomer cement (GIC) using two adhesive systems. A hole was prepared in 90 acrylic blocks (6 mm diameter, 2 mm deep) then filled with TheraCal LC, MTA or Fuji IX (n=30/group). Each group was bonded with either an etch and rinse or 1 step self-etch adhesive. Filtek Z250 composite was bonded to each capping material. Bond strength was tested in a universal testing machine, and data were analyzed using 2-way ANOVA and Duncan's Multiple range test (p<0.05). TheraCal LC displayed the highest SBS (p<0.001). MTA bonded with the 1-step self-etch adhesive showed the lowest SBS (p<0.001), while SBS of TheraCal LC and Fuji IX did not differ between either adhesive (p>0.05). TheraCal LC is the preferred choice in pulp capping procedures when using resin composite restorations. PMID- 27680035 TI - Epigallocatechin-3-gallate increased the push out bond strength of an epoxy resin sealer to root dentin. AB - This study aimed to investigate the effect of epigallocatechin-3-gallate (EGCG) from green tea extract on the push out bond strength of an epoxy resin sealer to root dentin. Seventy single root canal premolars were decoronated and instrumented. The roots were randomly irrigated with different final irrigation protocols (n=16): 17%EDTA (EDTA), 17%EDTA followed by 2.5%NaOCl (EDTA+NaOCl), 17%EDTA followed by 1 mg/mL EGCG (EDTA+EGCG) and 1 mg/mL EGCG (EGCG). Other six root canals were received only 2.5%NaOCl as a control group. One root from each group (n=1) was excluded and prepared for SEM investigation. All root canals were then obturated and horizontally sectioned to perform the push out test. EDTA+EGCG group had the highest bond strength (p<0.05). EGCG group showed higher bond strength than EDTA group (p<0.05). The use of EGCG as a final irrigant significantly increased the push out bond strength of an epoxy resin sealer to root dentin. PMID- 27680036 TI - Fracture toughness of seven resin composites evaluated by three methods of mode I fracture toughness (KIc). AB - This study compared the fracture toughness values of seven resin composites and analyzed the consistency of data values using three methods: compact tension, three point and four point bending for Mode I failure. Seven resin composites were selected: Estellite Sigma Quick, Esthet X HD, Filtek Supreme XTE, Heliomolar, Ice, Rok, and Vit-l-escence. For each material, 18 specimens (n=6 for each test) were prepared. Maximum load to failure was recorded using a universal testing machine and fracture toughness was calculated. There was a direct significant correlation among all tested methods. Rok showed the highest and Estelite the lowest KIc values. SEM of the fractured surface of compact tension method showed propagation of the cracks from stresses concentrating at the corner of the notch and the surface of the sample. Four-point test gave the largest range in KIc and was a simple method to discriminate between the resin composite values of KIc. PMID- 27680037 TI - Health and equity. PMID- 27680038 TI - Factors associated with the grief after stillbirth: a comparative study between Brazilian and Canadian women. AB - OBJECTIVE: To verify the association between complicated grief and sociodemographic, reproductive, mental, marital satisfaction, and professional support characteristics in women after stillbirth. METHOD: Cross-sectional study with 26 women who had stillbirth in 2013, living in the city of Maringa, Brazil, and eight women who attended the Centre d'Etudes et de Rechercheen Intervention Familiale at the University of Quebec en Outaouais, in Canada. The instrument was administered as an interview to a small number of mothers of infants up to three months (n=50), who did not participate in the validation study. RESULTS: By applying the short version of the Perinatal Grief Scale, the prevalence of complicated grief in Brazilian women was found to be higher (35%) in relation to Canadian women (12%).Characteristics of the Brazilian women associated with the grief period included the presence of previous pregnancy with live birth, absence of previous perinatal loss, postpartum depression, and lack of marital satisfaction. For the Canadians it was observed that 80% of the women presenting no grief made use of the professional support group. In both populations the occurrence of complicated grief presented a higher prevalence in women with duration of pregnancy higher than 28 weeks. CONCLUSION: The women that must be further investigated during the grief period are those living in Brazil, making no use of a professional support group, presenting little to no marital satisfaction, having no religion, and of a low educational level. OBJETIVO: Verificar aassociacao entre o luto complicado e as caracteristicas sociodemograficas, reprodutivas, mentais, de satisfacao conjugal e apoio profissional em mulheres apos obito fetal. METODO: Estudo transversal com 26 mulheres que tiveram obito fetal no ano de 2013 residentes no municipio de Maringa, Brasil, e 18 mulheres participantes do Centre d'Etudes et de Rechercheen Intervention Familiale, na Universidade do Quebec em Outaouais, no Canada. RESULTADOS: Por meio da aplicacao da versao curta da Perinatal Grief Scale, a prevalencia de luto complicado foi maior nas brasileiras (35%) em relacao as canadenses (12%). As caracteristicas das brasileiras associadas ao luto complicado foram a presenca de gestacao anterior com filho nascido vivo, nao ocorrencia de perda perinatal anterior, depressao pos-parto e nao satisfacao conjugal. Para as canadenses, foi observado que 80% das mulheres sem luto utilizaram grupo profissional de apoio. Nas duas populacoes a ocorrencia do luto complicado foi mais frequente nas mulheres com duracao na gestacao maior que 28 semanas. CONCLUSAO: As mulheres que mais devem ser investigadas no estado de luto sao as que moram no Brasil, que nao utilizam grupo profissional de apoio, nao tem satisfacao conjugal, nao praticam religiao e tem menor escolaridade. PMID- 27680039 TI - AIDS and jail: social representations of women in freedom deprivation situations. AB - OBJECTIVE: To graspthe AIDS social representations built by freedom-deprived women. METHOD: Descriptive study with a quali-quantitative approach that involved 174 convicted women in a women's prison in a capital city of the Brazilian northeastern region. Aword-association test was applied in October and November 2014, using AIDS as a stimulus. The corpuswas processed usingIramuteq software. Descending Hierarchical Classification and Correspondence Factor Analysis were applied. RESULTS: The content that comprises the social representation of AIDS was influenced by the prison context, which was pervaded by a lack of assistance, lack of knowledge, discrimination, and suffering that disclosed vulnerability to HIV/AIDS factors such as unprotected sex and object sharing. This underlines the stigma and fear of the illness, in addition to favoring and supporting negative feelings and a sense of rejection. CONCLUSION: To consider the use of this representational amalgam to ensure a comprehensive, contextualized care can help redirect practices, motivate self-care practices, and reduce prejudiced attitudes. OBJETIVO: Apreenderas representacoes sociais sobre a aids construidas por mulheres privadas de liberdade. METODO: Estudo descritivo, com abordagem quali-quantitativa que envolveu 174 apenadas de Presidio Feminino situado em capital do nordeste brasileiro. Aplicou-se o Teste de Associacao Livre de Palavras, em outubro e novembro de 2014, utilizando-se do estimulo aids. O corpus foi processado pelo software Iramuteq, sendo efetuadas a Classificacao Hierarquica Descendente e Analise Fatorial de Correspondencia. RESULTADOS: Os conteudos que compoem a representacao social sobre aids sao influenciados pelo contexto prisional, permeado dedesassistencia, desconhecimento, discriminacao e condicoes de sofrimento, revelando fatores de vulnerabilidade ao HIV/Aids como atividade sexual desprotegida e compartilhamento de objetos; reiterando o estigma e o temor a doenca; e favorecendo e sustentando sentimentos negativos e de rejeicao. CONCLUSAO: : Considerar este amalgama representacional na garantia de um cuidado integral e contextualizado pode contribuir para redirecionar praticas, motivar condutas de autocuidado e reduzir atitudes preconceituosas. PMID- 27680040 TI - Association between secondhand smoking in the home and respiratory morbidity in preschool children. AB - OBJECTIVE: Identifying the prevalence of secondhand smoking in the home and its association with morbidity and hospitalization from respiratory causes in preschool children. METHOD: This is a cross-sectional study conducted in five early childhood education centers at a public university in Sao Paulo. Sample size calculation was performed and the participants were randomly determined. Data were collected through questionnaires completed by family members or caregivers of 215 children. Chi-square and Student's t-test were used for the statistical analysis, using a 0.05 significance level. RESULTS: The prevalence of secondhand smoke in the household was 15.3%. Bivariate analysis revealed that secondhand smoke in the household was associated with the occurrence of rapid breathing, subdiaphragmatic retractions in the past three months, and treated ear infections/otitis. CONCLUSION: A low prevalence of secondhand smoking in the home was found. Secondhand smoke was associated with a higher prevalence of respiratory symptoms and morbidity. OBJETIVO: Identificar a prevalencia de tabagismo passivo em domicilio e verificar sua associacao com morbidades e hospitalizacao por causas respiratorias em criancas pre-escolares. METODO: Trata se de estudo transversal conduzido em cinco centros de educacao infantil de uma universidade publica de Sao Paulo. Foi realizado calculo de tamanho amostral, e a selecao dos participantes foi feita por sorteio. Os dados foram coletados por meio de questionarios preenchidos pelos familiares ou cuidadores de 215 criancas. Na analise estatistica foram empregados os testes Qui-quadrado e t-Student, considerando-se um nivel de significancia de 0,05. RESULTADOS: A prevalencia de tabagismo passivo em domicilio foi de 15,3%. Verificou-se na analise bivariada que o tabagismo passivo em domicilio esteve associado a ocorrencia de respiracao rapida, retracao subdiafragmatica nos ultimos tres meses, e otite tratada. CONCLUSAO: Verificou-se uma baixa prevalencia de tabagismo passivo domiciliar. O tabagismo passivo esteve associado a uma prevalencia maior de sintomas e morbidade respiratoria. PMID- 27680041 TI - Coping strategies of nurses in the care of patients with head and neck neoplasms. AB - OBJECTIVE: To understand and describe the experience of the development of coping strategies during the professional life of nurses providing care to patients with facial image alteration. METHOD: Descriptive qualitative study with a hermeneutic dialectic framework conducted in the head and neck ward of a reference hospital in Rio de Janeiro, with the participation of eight nurses and data produced through semi-structured interviews conducted between June and August 2013. RESULTS: Three major impressions were found: initial estrangement and complexity, consisting in the care given to patients with facial image alteration; a threshold between estrangement and coping, corresponding to the emergence of coping strategies during care; and image-likeness as a (re)cognition of the individual with facial image alteration in the development and consolidation of coping strategies during care. CONCLUSION: Among other contributions, the identification and understanding of coping strategies may contribute to better qualify nursing education and care. OBJETIVO: Compreender e descrever a experiencia de desenvolvimento de estrategias de enfrentamento durante a vida profissional de enfermeiras no cuidado aos pacientes com imagem facial alterada. METODO: Pesquisa qualitativa descritiva, com referencial hermeneutico-dialetico, realizada na Secao de Cabeca e Pescoco de um hospital de referencia do Rio de Janeiro, com participacao de oito enfermeiras e dados produzidos por meio de entrevista semiestruturada entre junho e agosto de 2013. RESULTADOS: Emergiram tres amplos sentidos: estranhamento e complexidade iniciais, que constituem o cuidado ao paciente com imagem facial alterada; limiar entre estranhamento e enfrentamento, correspondendo a emersao das estrategias de enfrentamento durante o cuidado; e imagem-semelhanca como (re)conhecimento da pessoa com imagem facial alterada no desenvolvimento e na consolidacao das estrategias de enfrentamento durante o cuidado. CONCLUSAO: Entre outras contribuicoes, a identificacao e a compreensao das estrategias de enfretamento podem contribuir para melhor qualificar a formacao e a assistencia de enfermagem. PMID- 27680042 TI - Use of a severity indicator as a predictor of the use of hepatic transplantation resources. AB - OBJECTIVE: To evaluate the use of a severity indicator for end-stage liver disease as a predictor of resource use in a teaching hospital in Sao Paulo. METHOD: Descriptive, retrospective study, classifying independent variables in seven key dimensions: identification/risk rating; length of stay/use of advanced life support; imaging; clinical analysis; special procedures; blood products in the intensive care unit; and in the operating room. The frequencies were analyzed by linear regression analysis of variance to detect relevance due to the dependent variable (severity indicator) in 76 cases seen in 2013. RESULTS: Among the variables studied, those that presented relevance due to the functional risk score were laboratory measurements of bilirubin, amylase, transaminase, blood count, creatine phosphokinase (p<0.05), hemotherapy procedures fresh frozen plasma (FFP) and platelet concentrate (p<0.05), and Doppler echocardiography image (p<0.07). CONCLUSION: Given the results/objective of this study, it is concluded that the indicator presents a potential predictive capability in the use of postoperative resources of liver receptors in the size, clinical analysis, images and hemotherapy dimensions. OBJETIVO: Avaliar o uso do indicador de gravidade para doencas hepaticas terminais como fator preditivo do uso de recursos em um hospital-escola de Sao Paulo. METODO: Estudo descritivo, retrospectivo, classificando variaveis independentes em sete dimensoes principais: identificacao/classificacao de risco; tempo de permanencia/uso de suporte avancado a vida; exames de imagem; analises clinicas; procedimentos especiais; hemoderivados em unidade de terapia intensiva; e em centro cirurgico. As frequencias foram analisadas por regressao linear com analise de variancia para deteccao de relevancias face a variavel dependente (indicador de gravidade) em 76 casos atendidos em 2013. RESULTADOS: Dentre as variaveis estudadas, apresentaram relevancia em funcao do escore de risco funcional as dosagens laboratoriais de bilirrubina, amilase, transaminase, hemograma, creatinofosfoquinase (p<0,05), procedimentos hemoterapicos plasma fresco congelado (PFC) e concentrado de plaquetas (p<0,05), e imagem Ecodoppler (p<0,07). CONCLUSAO: Face aos resultados/proposito do estudo conclui-se que o indicador apresenta potencial capacidade preditiva no uso de recursos pos operatorios de receptores de figado nas dimensoes, analises clinicas, imagens e hemoterapia. PMID- 27680043 TI - Incidence and factors related to delirium in an intensive care unit. AB - OBJECTIVES: To identify the incidence of delirium, compare the demographic and clinical characteristics of patients with and without delirium, and verify factors related to delirium in critical care patients. METHOD: Prospective cohort with a sample made up of patients hospitalized in the Intensive Care Unit (ICU) of a university hospital. Demographic, clinical variables and evaluation with the Confusion Assessment Method for Intensive Care Unit to identify delirium were processed to the univariate analysis and logistic regression to identify factors related to the occurrence of delirium. RESULTS: Of the total 149 patients in the sample, 69 (46.3%) presented delirium during ICU stay, whose mean age, severity of illness and length of ICU stay were statistically higher. The factors related to delirium were: age, midazolam, morphine and propofol. CONCLUSION: Results showed high incidence of ICU delirium associated with older age, use of sedatives and analgesics, emphasizing the need for relevant nursing care to prevent and identify early, patients presenting these characteristics. OBJETIVOS: Identificar a incidencia de delirium, comparar as caracteristicas demograficas e clinicas dos pacientes com e sem delirium e verificar os fatores relacionados ao delirium em pacientes internados em Unidade de Terapia Intensiva (UTI). METODO: Coorte prospectiva, cuja amostra foi constituida de pacientes internados em UTI de um hospital universitario. Variaveis demograficas, clinicas e da avaliacao com o Confusion Assessment Method for Intensive Care Unit para identificacao de delirium foram processadas para analise univariada, e regressao logistica para identificar fatores relacionados a ocorrencia do delirium. RESULTADOS: Do total de 149 pacientes da amostra, 69 (46,3%) apresentaram delirium durante a internacao na UTI, observando-se que a media da idade, o indice de gravidade e o tempo de permanencia nas UTI foram estatisticamente maiores. Os fatores relacionados ao delirium foram: idade, midazolam, morfina e propofol. CONCLUSAO: Os resultados mostraram elevada incidencia de delirium na UTI e sua ocorrencia associada as idades mais avancadas e o uso de sedativos e analgesicos, ressaltando-se a importancia da atuacao do enfermeiro na prevencao e identificacao precoce do quadro nos pacientes com essas caracteristicas. PMID- 27680044 TI - Elder-friendly emergency services in Brazil: necessary conditions for care. AB - OBJECTIVE: To identify and analyze the aspects necessary to provide an elder friendly emergency service (ES) from the perspective of nurses. METHOD: This is a descriptive, quantitative study using the Delphi technique in three rounds. Nurses with professional experience in the ES and/or researchers with publications and/or conducting research in the study area were selected. The first round of the Delphi panel had 72 participants, the second 49, and the third 44. An online questionnaire was used based on a review of the scientific literature with questions organized into the central dimensions of elder-friendly hospitals. A five-point Likert scale was used for each question and a 70% consensus level was established. RESULTS: There were 38 aspects identified as necessary for elderly care that were organized into central dimensions. CONCLUSIONS: The study's results are consistent with the findings in scientific literature and suggest indicators for quality of care and training for an elder friendly ES. OBJETIVO: Identificar e analisar aspectos necessarios para um atendimento amigo do idoso nos servicos de emergencia (SE), na perspectiva de enfermeiros. METODO: Estudo descritivo, quantitativo, com utilizacao da Tecnica Delphi, em tres rodadas. Foram selecionados enfermeiros com experiencia profissional em SE e/ou pesquisadores com publicacoes e/ou desenvolvendo pesquisas na area de estudo. A primeira rodada do painel Delphi contou com 72 participantes, a segunda com 49 e a terceira com 44. Foi utilizado questionario on-line, baseado na revisao da literatura cientifica, com questoes organizadas em dimensoes centrais de hospitais amigos do idoso. Foi utilizada uma escala de Likert de 5 pontos para cada questao e estabelecido nivel de consenso de 70%. RESULTADOS: Foram identificados 38 aspectos necessarios para o atendimento ao idoso, organizados em dimensoes centrais. CONCLUSOES: Os resultados do estudo sao consistentes com os achados na literatura cientifica e sugerem indicadores para qualidade do cuidado e para formacao de SE amigos do idoso. PMID- 27680045 TI - Indicators of health and safety among institutionalized older adults. AB - OBJECTIVE: To identify the incidence of mortality, diarrheal diseases, scabies and falls; and the prevalence of pressure ulcers - all of which are related to the safety ofinstitutionalized older adults. METHOD: This was a documentary retrospective study developed in a long-term residential careinstitution for older adults in the Northeast region of Brazil. The data were gathered from records of health assessment indicators filed between January 2008 and December 2015. Analysis included absolute case frequency; the sum of monthly prevalence and incidence rates; mean values of cases; and mean annual incidence and prevalence rates. RESULTS: The incidence of mortality over these nine years ranged from 9% to 13%; of acute diarrheic disease from 13% to 45%; and scabies from 21% to 63%. The prevalence of pressure ulcers ranged from 8% to 23%. Between 2012 and 2015, the incidence rate of falls without injury varied from 38% to 83%, and with injury from12% to 20%. CONCLUSION: Analysis of the health indicators revealeda high incidence of scabies and falls and a high prevalence of pressure ulcers. The identification of less than optimal rates for performance indicators canhelp improve the quality of nursing care. OBJETIVO: Identificar a incidencia de mortalidade, doencas diarreicas, escabiose e quedas, e a prevalencia de lesoes por pressao para a seguranca do idoso institucionalizado. METODO: Estudo documental, retrospectivo desenvolvido em uma Instituicao de Longa Permanencia para Idosos, localizada no nordeste do Brasil. Os dados foram coletados por meio dos registros dos indicadores de avaliacao de saude, arquivados de janeiro de 2008 a dezembro de 2015. A analise incluiu a frequencia absoluta dos casos; o somatorio das taxas de prevalencia e incidencia mensais; a media de casos e das taxas de incidencia e prevalencia anuais. RESULTADOS: Observa-se que a incidencia de obitos nos nove anos considerados variou de 9 a 13%; de doencas diarreicas agudas, de 13 a 45%; e de escabiose, de 21 a 63%. A prevalencia de lesao por pressao oscilou de 8 a 23%. Entre os anos de 2012 a 2015, a taxa de incidencia de quedas sem lesao variou em torno de 38 a 83%, e com lesao, de 12 a 20%. CONCLUSAO: A analise da amplitude dos indicadores de saude permitiu identificar a alta incidencia de escabiose e de quedas e a elevada prevalencia de lesoes por pressao. A identificacao do comprometimento dos indicadores contribui para otimizacao da qualidade da assistencia de enfermagem. PMID- 27680046 TI - Nursing terminology as a work process instrument of nurses in collective health. AB - OBJECTIVE: To analyze the use of nursing terminology as an instrument of the nursing work process in Collective Health. METHOD: Exploratory case study. For data collection was conducted a group interview with 24 nurses working in health units of a municipality in south central Parana, Brazil. Data were analyzed in the light of interdependence between the structural, particular and singular dimensions contained in the Theory of Nursing Praxis Intervention in Collective Health. RESULTS: The situations interfering with improper use were the lack of knowledge about the origin and purpose of terminology, lack of training, and non mandatory use. CONCLUSION: Although the nursing terminology is used as an instrument in the nursing work process in collective health, it requires training to be recognized as a classification system. At the same time, institutional policies should be employed to ensure the effective use of these instruments. OBJETIVO: Analisar a utilizacao de terminologia de enfermagem como instrumento do processo de trabalho do enfermeiro em Saude Coletiva. METODO: Estudo de caso exploratorio. Para coleta de dados foi realizada entrevista em grupo com 24 enfermeiros que atuam nas unidades de saude de um municipio no centro-sul do Parana, Brasil. Os dados foram analisados a luz da interdependencia entre as dimensoes estrutural, particular e singular contidas na Teoria da Intervencao Praxica de Enfermagem em Saude Coletiva. RESULTADOS: As situacoes que interferiram na utilizacao inadequada foram o desconhecimento sobre origem e finalidade da terminologia, a falta de treinamento e a nao obrigatoriedade de uso. CONCLUSAO: A terminologia de enfermagem, apesar de utilizada como instrumento no processo de trabalho de enfermeiros em Saude Coletiva, necessita de capacitacao para ser reconhecida como sistema classificatorio. Ao mesmo tempo, politicas institucionais devem ser empregadas no intuito de garantir a efetiva utilizacao destes instrumentos. PMID- 27680047 TI - Staphylococcus aureus and the oxacillin sensitivity profile in hospitalized people with HIV/AIDS. AB - Objective: Analyze nasal colonization by oxacillin-sensitive and oxacillin resistant Staphylococcus aureus in people with HIV/AIDS (PWHA) at days 1 and7 of hospitalization. METHOD: A prospective observational study conducted in a hospital in the countryside of the state of Sao Paulo. Nasal swab samples were collected and analyzed through microbiological identification, at days 1 and 7 of hospitalization of PWHA, between August 2011 and January 2014. Data were analyzed via IBM SPSS(r), version 20.0. RESULTS: Nasal secretion samples were collected from 187 (50.1%) PWHA at days 1 and 7 of hospitalization. Of these, Staphylococcus aureus was identified in 64 (34.2%) PWHA. CONCLUSION: At day 1 of hospitalization, 27 PWHA were identified with Staphylococcus aureus; 27 PWHA presented colonization by Staphylococcus aureus at days 1 and 7, and 10 PWHA only at day 7. Of 64 PWHA colonized by Staphylococcus aureus, the susceptibility profile of isolated Staphylococcus aureus was oxacillin-resistant in 25 PWHA. OBJETIVO: Analisar a colonizacao nasal por Staphylococcus aureus sensiveis e resistentes a oxacilina de pessoas vivendo com HIV/aids (PVHA) no primeiro e no setimo dia de internacao hospitalar. METODO: Estudo prospectivo observacional realizado em um hospital do interior paulista. Foram coletadas e analisadas, por meio de identificacao microbiologica, amostras de swab nasal no primeiro e no setimo dia de internacao hospitalar de PVHA, no periodo de agosto/2011 e janeiro/2014. A analise dos dados foi realizada por meio do IBM SPSS(r), versao 20.0. RESULTADOS: Em 187 (50,1%) PVHA foram coletadas amostras de secrecao nasal no primeiro e setimo dia de internacao. Destas, em 64 (34,2%) foi identificado Staphylococcus aureus. CONCLUSAO: No primeiro dia de internacao observou-se 27 PVHA colonizadas por Staphylococcus aureus; em 27 PVHA houve a persistencia da colonizacao por Staphylococcus aureus no primeiro e no setimo dia; em 10 PVHA, somente no setimo dia. Das 64 PVHA colonizadas por Staphylococcus aureus, em 25 o perfil de suscetibilidade do Staphylococcus aureus isolado foi resistente a oxacilina. PMID- 27680048 TI - Differences in the clinical-epidemiological profile between new cases of tuberculosis and retreatment cases after default. AB - OBJECTIVE: To identify the socioeconomic and clinical-epidemiological factors related to tuberculosis in new cases and retreatment cases. METHOD: Comparative study with 126 patients, of which 42 were retreatment cases after default attended in a reference center, and 84 were new cases completing the first treatment and treated in Basic Health Units. The collection of primary data was through interview, and of secondary data by records of the Notifiable Diseases Information System. Comparative analysis between the two groups. RESULTS: The new cases differ from retreatment cases regarding educational level. The clinical epidemiological profile shows a significant difference in relation to performance of the tuberculin skin test, and the HIV test result (positive) in favor of new cases. In relation to performance of sputum culture and the result (positive) of the first sputum smear of the first and second samples, in favor of retreatment cases. CONCLUSION: The two groups are significantly different in clinical and epidemiological characteristics that show the access to exams. OBJETIVO: Identificar fatores socioeconomicos e clinico-epidemiologicos associados a tuberculose em casos novos e em casos em retratamento. METODO: Estudo comparativo de 126 pacientes, sendo 42 casos em retratamento por abandono atendidos num Centro de Referencia e 84 casos novos concluindo o primeiro tratamento, atendidos em Unidades Basicas de Saude. Levantamento de dados primarios por entrevista e dados secundarios pela Ficha de Informacao de Agravos de Notificacao. Analise comparativa entre os dois grupos. RESULTADOS: Os casos novos diferem dos em retratamento quanto a escolaridade. O perfil clinico-epidemiologico mostra que ha diferenca significativa quanto a realizacao do teste tuberculinico e o resultado do teste HIV (positivo) a favor dos casos novos. Quanto a realizacao da cultura de escarro e o resultado (positivo) da baciloscopia de escarro da primeira e da segunda amostras, a favor dos casos em retratamento. CONCLUSAO: Os dois grupos diferem significativamente por caracteristicas clinico-epidemiologicas que retratam o acesso a exames. PMID- 27680049 TI - Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers. AB - OBJECTIVE: To evaluate the effects of low-level laser therapy isolated and associated with Calendula officinalis oil in treating diabetic foot ulcers. METHOD: An experimental, randomized, controlled, prospective, interventional clinical case study using a quantitative approach. The sample consisted of 32 diabetic patients of both genders. Participants were randomly divided into four groups. Doppler Ultrasound evaluation of the Ankle-Brachial Index, brief pain inventory and analog pain scale were performed at baseline and after 30 days. RESULTS: Reduced pain was observed in the Low-level laser therapy and Low-level laser therapy associated with Essential Fatty Acids groups (p<0.01). Regarding the Ankle-Brachial Index and Doppler Ultrasound, all groups remained stable. By analyzing lesion area reduction, Low-level laser therapy associated with Essential fatty acids group showed a significance of p=0.0032, and the Low-level laser therapy group showed p=0.0428. CONCLUSION: Low-level laser therapy, performed alone or associated with the Calendula officinalis oil was effective in relieving pain and accelerating the tissue repair process of diabetic foot. OBJETIVO: Avaliar os efeitos da Terapia a Laser de Baixa Intensidade isolada e associada ao oleo de Calendula officinalis no reparo de ulceras em pe diabetico. METODO: Estudo de caso clinico, experimental, controlado, randomizado, prospectivo, intervencional, de carater quantitativo. A amostra foi composta de 32 pacientes diabeticos, de ambos os generos. Os participantes foram distribuidos aleatoriamente em quatro grupos. Ultrassom Doppler, avaliacao do Indice Tornozelo Braquial, Inventario breve de dor e escala de dor analogica foram realizados no inicio e apos 30 dias. RESULTADOS: Houve reducao da dor nos grupos Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa intensidade associada aos Acidos Graxos Essenciais, com p<0,01. Quanto ao Indice Tornozelo-Braquial e Ultrassom Doppler, todos os grupos mantiveram-se estaveis. Na analise da reducao de area da lesao, o grupo Terapia a Laser de Baixa Intensidade associada aos Acidos Graxos Essenciais apresentou uma significancia p=0,0032, e o grupo Terapia a Laser de Baixa Intensidade, p=0,0428. CONCLUSAO: A Terapia a Laser de Baixa Intensidade, realizada tanto isoladamente quanto associada ao oleo de Calendula officinalis, foi eficaz no alivio da dor e na aceleracao do processo de reparo tecidual de pe diabetico. PMID- 27680050 TI - Impact of promoting self-care in nursing workload. AB - OBJECTIVES: To assess the impact of promoting self-care in nursing workload and associate it to the variables: age, gender, socioeconomic status, education, marital status and number of children of caregivers. METHODS: Prospective study with 31 children and their caregivers. Participants were assessed at two moments, 1st and 2nd hospitalization, the nursing workload was measured by the Nursing Activities Score (NAS). RESULTS: The mean NAS in the 1st hospitalization was 60.9% and in the 2nd hospitalization was 41.6%, that is, 14.6 and 9.9 hours of nursing, respectively. The nursing workload on the first day of hospitalization was higher compared to the last day, both for the 1st (p<0.001) and for the 2nd hospitalization (p<0.001), and higher in the first (p<0.001) and in the last day (p=0.025) in the 1st hospitalization. Comparing the 1st hospitalization to the 2nd hospitalization, the first was higher (p<0.001), and NAS items related to the training of self-care was influenced (p<0.001). CONCLUSION: The nursing workload associated to self-care promotion corresponded to 14.6 hours and was higher than determined by the existing legislation. OBJETIVOS: Verificar o impacto da promocao do autocuidado na carga de trabalho de enfermagem e associa-la as variaveis: idade, genero, classificacao socioeconomica, escolaridade, estado civil e numero de filhos dos cuidadores. METODO: Estudo prospectivo, onde participaram 31 criancas e seus respectivos cuidadores. Os participantes foram avaliados em dois momentos, 1a e 2a internacao, quanto a carga de trabalho de enfermagem mensurada por meio do Nursing Activities Score (NAS). RESULTADOS: A media NAS na 1a internacao foi de 60,9%, e na 2a internacao foi de 41,6%, ou seja, 14,6 e 9,9 horas de enfermagem, respectivamente. A carga de trabalho de enfermagem no primeiro dia de internacao foi maior quando comparada ao ultimo dia, tanto na 1a (p<0,001) como na 2a internacao (p<0,001), e maior no primeiro (p<0,001) e ultimo dia (p=0,025) na 1a internacao. Ainda, na 1a internacao, foi maior quando comparada a 2a internacao (p<0,001), e os itens NAS referentes a capacitacao do autocuidado a influenciaram (p<0,001). CONCLUSAO: A carga de trabalho de enfermagem referente a promocao do autocuidado correspondeu a 14,6 horas e foi superior ao determinado pela legislacao existente. PMID- 27680051 TI - Teamwork in nursing: restricted to nursing professionals or an interprofessional collaboration? AB - OBJECTIVE: To understand the nursing professionals' conceptions of teamwork and their elements. METHOD: A qualitative study conducted in an oncological hospital using a semi-structured interview with 21 nursing professionals. RESULTS: Two conceptions emerged from the accounts: teamwork restricted to nursing professionals and teamwork with interprofessional collaboration with particular importance for interactive dimensions: communication, trust and professional bonds, mutual respect and recognition of the other's work, collaboration, and conflict, with this last subcategory considered as an obstacle to teamwork. CONCLUSION: Nursing conceives teamwork as an interprofessional practice, which is a result of the quality of interaction among professionals from different areas and involves the recognition and handling of conflicts. OBJETIVO: Compreender as concepcoes dos profissionais de enfermagem sobre trabalho em equipe e seus elementos constituintes. METODO: Pesquisa qualitativa, realizada em hospital oncologico, por meio de entrevista semiestruturada com 21 profissionais de enfermagem. RESULTADOS: Duas concepcoes emergiram dos relatos, trabalho em equipe circunscrito a enfermagem e trabalho em equipe com colaboracao interprofissional, com destaque para dimensao interativa: comunicacao, confianca e vinculo, respeito mutuo e reconhecimento do trabalho do outro, colaboracao e conflito. Esta ultima subcategoria foi apontada como obstaculo para o trabalho em equipe. CONCLUSAO: A enfermagem concebe majoritariamente o trabalho em equipe como acao interprofissional, e isto decorre da qualidade da interacao entre os profissionais das diferentes areas e o reconhecimento e manejo de conflitos. PMID- 27680052 TI - Is there any link between accreditation programs and the models of organizational excellence? AB - OBJECTIVE: To evaluate whether accredited health organizations perform better management practices than non-accredited ones. METHOD: The study was developed in two stages: a literature review, and a study of multiple cases in 12 healthcare organizations in the state of Sao Paulo, Brazil. It surveyed articles comparing hospital accreditation with the EFQM (European Foundation for Quality Management) model of excellence in management. According to the pertinent literature, the accreditation model and the EFQM model are convergent and supplementary in some aspects. RESULTS: With 99% confidence, one can say that there is evidence that accredited organizations scored better in the evaluation based on the EFQM model in comparison to non-accredited organizations. This result was also confirmed in the comparison of results between the categories Facilitators and Results in the EFQM model. CONCLUSION: There is convergence between the accreditation model and the EFQM excellence model, suggesting that accreditation helps the healthcare sector to implement the best management practices already used by other business sectors. OBJETIVO: Avaliar se as organizacoes de saude acreditadas possuem melhores praticas de gestao do que as nao acreditadas. METODO: A pesquisa foi dividida em duas etapas: revisao da literatura e estudo de casos multiplos com 12 organizacoes de saude, localizadas no estado de Sao Paulo - Brasil. Foram pesquisados artigos que comparavam a acreditacao hospitalar com o modelo de excelencia em gestao da EFQM (European Foundation for Quality Management), sendo que a literatura pertinente considera que o modelo de acreditacao e o modelo da EFQM sao convergentes e, ao mesmo tempo, complementares em determinados aspectos. RESULTADOS: Com 99% de confianca, pode-se afirmar que ha evidencia de que as organizacoes com acreditacao obtiveram uma pontuacao maior na avaliacao baseada no modelo EFQM comparativamente as organizacoes nao acreditadas. Este resultado tambem se confirmou na comparacao dos resultados das categorias Facilitadores e Resultados do modelo EFQM. CONCLUSAO: Ha uma convergencia entre o modelo de acreditacao e o modelo de excelencia da EFQM, sugerindo que a acreditacao contribui para o setor de saude implementar as melhores praticas de gestao ja difundidas em outros setores de negocio. PMID- 27680053 TI - Instruments used in the assessment of expectation toward a spine surgery: an integrative review. AB - OBJECTIVE: To identify and describe the instruments used to assess patients' expectations toward spine surgery. METHOD: An integrative review was carried out in the databases PubMed, CINAHL, LILACS and PsycINFO. RESULTS: A total of 4,402 publications were identified, of which 25 met the selection criteria. Of the studies selected, only three used tools that had confirmed validity and reliability to be applied; in five studies, clinical scores were used, and were modified for the assessment of patients' expectations, and in 17 studies the researchers developed scales without an adequate description of the method used for their development and validation. CONCLUSION: The assessment of patients' expectations has been methodologically conducted in different ways. Until the completion of this integrative review, only two valid and reliable instruments had been used in three of the selected studies. OBJETIVO: Identificar e descrever os instrumentos usados para avaliar a expectativa dos pacientes diante do tratamento cirurgico da coluna vertebral. METODO: Revisao Integrativa realizada nas bases de dados PubMed, CINAHL, LILACS e PsycINFO. RESULTADOS: Identificamos 4.402 publicacoes, das quais 25 atenderam aos criterios de selecao. Dos estudos selecionados, apenas em tres os autores utilizaram instrumentos que possuiam validade e confiabilidade confirmadas para serem aplicados; em cinco estudos foram utilizados escores clinicos, modificados para a avaliacao das expectativas dos pacientes, e em dezessete os pesquisadores elaboraram escalas sem adequada descricao do metodo usado para o seu desenvolvimento e validacao. CONCLUSAO: A avaliacao das expectativas dos pacientes tem sido metodologicamente conduzida de diferentes maneiras. Ate a finalizacao desta revisao integrativa, apenas dois instrumentos, validos e confiaveis, haviam sido utilizados em tres dos estudos selecionados. PMID- 27680054 TI - Concepts and measures of patient empowerment: a comprehensive review. AB - OBJECTIVE: Analyze the definitions and dimensions of empowerment. Identify the strengths and weaknesses of empowerment measures based on the conceptual model. METHOD: This was a comprehensive literature review of publications on the MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. RESULTS: Twenty-nine articles were selected. Seventeen definitions and seven dimensions of empowerment, and 10 empowerment measures were selected. Empowerment can be seen as an enabling process involving a shift in the balance of power, or as an outcome of this process. The dimensions reflect outcome indicators, such as participation in decision-making and control, and process indicators, such as knowledge acquisition and coping skills. Six of the tools analyzed by this study could be said to provide a robust measure of patient empowerment. CONCLUSION: we propose a definition of empowerment that helps to deepen understanding of the term and, therefore, its operationalization. OBJETIVO: Analizar definiciones y dimensiones de empoderamiento. Identificar fortalezas y debilidades de los instrumentos de medida de empoderamiento respecto al modelo conceptual. METODO: Revision integrativa de la literatura en las bases de datos MEDLINE y Cumulative Index to Nursing and Allied Health Literature (CINAHL). RESULTADOS: Fueram seleccionados 29 articulos . Se identificaron 17 definiciones, 7 propuestas de dimensiones y 10 instrumentos de medida. Empoderamiento puede ser un proceso de capacitacion o habilitacion en el que se transfiere el poder de un individuo a otro, o bien un resultado producto de ese proceso. Las dimensiones reflejan indicadores de resultados como son la participacion en la toma de decisiones y tomar el control, e indicadores relativos al proceso como son la adquisicion de conocimientos y las habilidades de afrontamiento. De los instrumentos analizados seis son los instrumentos que presentan mayor robustez. CONCLUSION: Se propone una definicion de empoderamiento que puede ayudar a mejorar la comprension del termino y por lo tanto a operacionalizarlo. PMID- 27680055 TI - Family caregivers: what do they need? An integrative review. AB - OBJECTIVE: Aimed to identify the main needs expressed by family caregivers in caring for adependent person. METHOD: An integrative review of the literature in the period between 2010 and 2015 using specific search engine tools in the EBSCO and SCOPUSdatabases. RESULTS: 11 articles were selected, and the analysis of the scientific evidence obtained allowed for organizing the results into five thematic areas:transition into care, being responsible for everything, the importance of support, access to formal support, communication and informationprocesses. CONCLUSION: The results showed that caregivers have many needs in different areas, which should be addressed in nursing interventions. OBJETIVO: Este estudo teve como objetivo identificar quais as principais necessidades manifestadas pelo cuidador familiar no cuidado a pessoa dependente. METODO: Realizou-se uma revisao integrativa da literatura no periodo entre 2010 e 2015 com o recurso de instrumentos de busca especificos, nas bases de dados EBSCO e SCOPUS. RESULTADOS: Foram selecionados 11 artigos A analise da evidencia cientifica obtida permitiu organizar os resultados em cinco areas tematicas: a transicao para o cuidar, o ser responsavel por tudo, a importancia do suporte, o acesso aos apoios formais, a comunicacao e a informacao na tomada de decisao. CONCLUSAO: Os resultados demonstram que o cuidador apresenta inumeras necessidades em areas distintas,as quais devem ser abordadasnas intervencoes de enfermagem. PMID- 27680056 TI - Nursing workload and occurrence of adverse events in intensive care: a systematic review. AB - OBJECTIVE: To identifyevidences of the influence of nursing workload on the occurrence of adverse events (AE) in adult patients admitted to the intensive care unit (ICU). METHOD: A systematic literature review was conducted in the databases MEDLINE, CINAHL, LILACS, SciELO, BDENF, and Cochrane from studies in English, Portuguese, or Spanish, published by 2015. The analyzed AE were infection, pressure ulcer (PU), patient falls, and medication errors. RESULTS: Of 594 potential studies, eight comprised the final sample of the review. TheNursing Activities Score (NAS; 37.5%) and the Therapeutic Intervention Scoring System(TISS; 37.5%) were the instruments most frequently used for assessing nursing workload. Six studies (75.0%) identified the influence of work overload in events of infection, PU, and medicationerrors. An investigation found that the NAS was a protective factor for PU. CONCLUSION: The nursing workload required by patients in the ICU influenced the occurrence of AE, and nurses must monitor this variable daily to ensure proper sizing of staff and safety of care. OBJETIVO: Identificar evidencias sobre a influencia da carga de trabalho de enfermagem na ocorrencia de eventos adversos (EA) em pacientes adultos internados em Unidade de Terapia Intensiva (UTI). METODO: Revisao sistematica da literatura realizada nas bases de dados MEDLINE, CINAHL, LILACS, SciELO, BDENF e Cochrane deestudosem ingles, portugues ou espanhol, publicados ate 2015. Os EA analisados foram infeccao, ulcera por pressao (UPP), quedas e erros associados a medicamentos. RESULTADOS: Das 594 pesquisas potenciais identificadas, oito compuseram a amostra final da revisao. O NursingActivities Score -NAS (37,5%) e o TherapeuticInterventionScoring System -TISS (37,5%) foram os instrumentos mais utilizados para avaliacao da carga de trabalho de enfermagem. Seis pesquisas (75,0%) identificaram influencia da sobrecarga de trabalho na ocorrencia de infeccao, UPP e uso de medicamentos. Uma investigacao identificou que o NAS foi fator de protecao para UPP. CONCLUSAO: A carga de trabalho de enfermagem requerida por pacientes na UTI influenciou a ocorrencia de EA, e os enfermeiros devem monitorar diariamente esta variavel para garantir o correto dimensionamento da equipe e a seguranca da assistencia prestada. PMID- 27680057 TI - Analyzing the concept of disruptive behavior in healthcare work: an integrative review. AB - OBJECTIVE: To analyze the concept of disruptive behavior in healthcare work. METHOD: An integrative review carried out in the theoretical phase of a qualitative research substantiated by the theoretical framework of the Hybrid Model of Concept Development. The search for articles was conducted in the CINAHL, LILACS, PsycINFO, PubMed and SciVerse Scopus databases in 2013. RESULTS: 70 scientific articles answered the guiding question and lead to attributes of disruptive behavior, being: incivility, psychological violence and physical/sexual violence; with their main antecedents (intrapersonal, interpersonal and organizational) being: personality characteristics, stress and work overload; and consequences of: workers' moral/mental distress, compromised patient safety, labor loss, and disruption of communication, collaboration and teamwork. CONCLUSION: Analysis of the disruptive behavior concept in healthcare work showed a construct in its theoretical stage that encompasses different disrespectful conduct adopted by health workers in the hospital context, which deserve the attention of leadership for better recognition and proper handling of cases and their consequences. OBJETIVO: Analisar o conceito comportamento destrutivo no trabalho em saude. METODO: Revisao integrativa realizada na fase teorica de pesquisa qualitativa fundamentada pelo referencial teorico metodologico do Modelo Hibrido de Analise de Conceitos. A busca dos artigos foi realizada nas bases de dados CINAHL, LILACS, PsycINFO, PubMed e SciVerse Scopus, em 2013. RESULTADOS: 70 artigos cientificos responderam a questao norteadora e atenderam aos criterios de inclusao, permitindo evidenciar os atributos do comportamento destrutivo: incivilidade, violencia psicologica e violencia fisica/sexual; seus principais antecedentes (intrapessoais, interpessoais e organizacionais): caracteristicas de personalidade, estresse e sobrecarga de trabalho; e consequentes: sofrimento moral/psiquico dos trabalhadores, comprometimento da seguranca do paciente, prejuizos laborais, rompimento da comunicacao, da colaboracao e do trabalho em equipe. CONCLUSAO: A analise do conceito comportamento destrutivo no trabalho em saude evidenciou, em sua fase teorica, um constructo que abrange diferentes condutas desrespeitosas adotadas por trabalhadores de saude no contexto hospitalar, merecendo atencao de liderancas da area para maior reconhecimento e manejo adequado dos casos e suas consequencias. PMID- 27680058 TI - Locoregional treatment of peritoneal sarcomatosis A single-centre experience. AB - BACKGROUND: Peritoneal sarcomatosis appears to be responding poorly to systemic chemotherapy. Treatment options traditionally include surgical ressections, chemotherapy and radiation therapy. Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) offers a promising alternative locoregional treatment option. PATIENTS AND METHODS: We examine retrospectively 8 patients (4 females, 4 males) with peritoneal sarcomatosis. The most common histology type was the liposarcoma (4/8). The chemotherapeutic agents that were administered were mitomycin, cisplatin and doxorubicin. We analyse our cases with regard to the PCI, the CC score, the complications that occurred and the overall survival. RESULTS: A complete level of cytoreduction (CC0/1) was feasible in 5/8 of patients. We report post-operative complications such as GI leaks and fistulas in 3 cases and infections in 2 cases. Overall survival was proved to depend on the PCI (better overall survival rate when PCI<20) DISCUSSION: We identify acceptable morbidity, comparable to other series of patients undergoing CRS+HIPEC for other histologies. The specific sarcoma type and the previous treatment received prove to be factors that alter significantly the prognosis and the survival rates: therefore, conclusions cannot be safely excluded in such small patient series. On the whole, we conclude that, given the already positive and promising results from CRS+HIPEC in sarcomatosis, more studies need to be performed, in order to determine the role of all the aforementioned factors. KEY WORDS: Fibrosarcoma, HIPEC, Leiomyosarcoma, Liposarcoma, Rabdomyosarcoma, Sarcomatosis. PMID- 27680059 TI - [Consensus and controversies of surgical approach selection in the treatment for thoracic esophageal cancers]. AB - Esophageal cancer is one of the most prevalent carcinoma with an incidence ranking at the fifth and the mortality at the fourth among all the carcinomas in China. Up to now, surgery-based multi-modality treatment is still the most effective treatment for esophageal carcinoma. The surgical approaches for esophageal cancer include left and right thoracic approaches. Esophagectomy through left thoracotomy is the earliest approach applied for esophageal cancer in China, and now is still used frequently for esophageal cancer in northern China. However, left thoracic approach is insufficient in the lymph node dissection for superior mediastinum and abdomen, especially for the tracheoesophageal groove and para-recurrent laryngeal nerve nodes. On the contrary, right thoracic approach can achieve complete thoracic and abdominal field(two-field) lymph node dissection, especially the tracheoesophageal groove and para-recurrent laryngeal nerve nodes, which may eventually improve the survival of the patients with esophageal cancer. This article summarizes the results of lymph node dissection and prognosis based on published literatures through left thoracic approach versus through right thoracic approach for esophageal cancer, comments on recent controversies and consensus: for resectable thoracic esophageal carcinoma, resection of thoracic esophageal carcinoma with 2 field or 3-field lymph node dissection through right thoracic approach should be recommended as the major treatment mode, but this consensus was made based on retrospective studies, and the evidence is only level III(, therefore, prospective randomized studies with larger sample size are warranted. The selection of surgical approach for the lower thoracic esophageal cancer patients without upper mediastinal lymph node enlargement is also the direction of future clinical trials. PMID- 27680061 TI - [Evaluation of the selection between thoracoscopic and open esophagectomy]. AB - Esophageal cancer is one of the most common digestive tract cancers in our country. Although multimodality therapy has been used in the treatment of esophageal cancer, such as radiotherapy, chemotherapy and targeted therapy, surgery plays its irreplaceable role. With the development of techniques and innovation of instruments, minimally invasive esophagectomy is introduced into practice worldwide. Due to its less trauma and fewer complications, minimally invasive esophagectomy draws great attention, however, controversy exists in the question whether minimally invasive esophagectomy has similar efficacy to open esophagectomy. With the aim of providing suggestions for selecting optimal surgical procedure, this review discusses differences between minimally invasive esophagectomy and open esophagectomy in the following three aspects: perioperative mortality and morbidity, margin status and harvested lymph node number, and postoperative survival. Nowadays, the advantage of minimally invasive esophagectomy has been widely recognized in reducing perioperative morbidity and mortality, however, in the aspect of radicality and prognosis, it is far from reaching a definite conclusion for lack of multicenter, large sample, prospective, randomized controlled trials. Such trials are warrented so as to show the strength and weakness of minimally invasive esophagectomy. PMID- 27680060 TI - [Strategy and prospective of enhanced recovery after surgery for esophageal cancer]. AB - Enhanced recovery after surgery (ERAS) is a patient-centered, surgeon-led system combining anesthesia, nursing, nutrition and psychology. It aims to minimize surgical stress and maintain physiological function in perioperative care, thereby expediting recovery. ERAS theory has been clinically applied for nearly 20 years and it is firstly used in colorectal surgery, then widely used in other surgical fields. However, ERAS is not used commonly in esophagectomy because of its surgical complexity and high morbidity of postoperative complications, which limits the application of ERAS in the field of esophagectomy. In recent years, with the increasing maturation of minimally invasive esophagectomy, attention to tissue and organ protection concept, improvement of making gastric tube, breakthrough of anastomosis technique, and the presentation and application of new concepts, ERAS has made great progress in the field of esophagectomy. This article summarizes some ERAS measures in the treatment of esophageal cancer based on evidence-based medicine, and performs an effective ERAS mode for clinical application of esophagectomy. During preoperative preparation and evaluation, we propose preoperative education and nutrition evaluation without regular intestinal preparation, and advocate preemptive analgesia without preanesthetic medication. During intra-operative management, anesthesia scheme should be optimized, fluid transfusion should be controlled properly, suitable operation mode should be chosen, and intraoperative hypothermia should be avoided. During postoperative management, sufficient analgesia should be administered with non opioid analgesics, drainage tube placement must be decreased and removed earlier, urinary catheter and gastrointestinal decompression tube should be removed earlier, and oral intake and ambulation should be resumed as early as possible. "Received surgery yesterday, oral intake today, discharged home 5-7 days", ERAS program based on "non tube no fasting" has been applied in some medical centers and becomes more and more maturation. In the future, we will rely on the increasing improvement and systemic training of ERAS mode in order to promote such application in more medical centers. With the multi-center clinical trials, based on constant enrichments and improvements, a general expert consensus will be made finally. PMID- 27680062 TI - [Optimal lymphadenectomy for thoracic esophageal cancer: three-field or modified two-field lymphadenectomy]. AB - Differences in operative procedure and knowledge of esophageal cancer exist among surgeons from different countries and regions. There is controversy in the surgical treatment of esophageal cancer, especially in the extent of lymphadenectomy. Until now, results of the three-field lymphadenectomy and two field lymphadenectomy are mostly reported by retrospective studies from Japan and China. Three-field lymphadenectomy has been initiated in Fujian Provincial Cancer Hospital since 1990s. After evaluating our database, we found that three-field was superior to two-field lymphadenectomy in terms of long-term survival for patients with upper thoracic esophageal cancer, whereas for those with middle or lower thoracic esophageal cancer, the survival benefit of three-field lymphadenectomy was reduced. Therefore, we propose to perform three-field lymphadenectomy for upper thoracic esophageal cancer. In middle or lower thoracic esophageal cancer, we suggest to perform modified two-field lymphadenectomy in most cases, and three-field lymphadenectomy in selective cases. Video-assisted two-field lymphadenectomy is feasible. Based on the national condition of China, we advise to perform thoracic duct removal only in patients with posterior mediastinal or peri-ductus node metastasis to achieve curative effect. PMID- 27680064 TI - [Study on the association of gastric conduit width and postoperative early delayed gastric emptying in middle-lower esophageal cancer patients undergoing Ivor-Lewis procedure]. AB - OBJECTIVE: To examine the relationship between gastric conduit width and postoperative early delayed gastric emptying (DGE) in patients with middle-lower esophageal carcinoma who underwent Ivor-Lewis operation. METHODS: Clinical data of 282 consecutive patients with middle-lower esophageal cancer who underwent the Ivor-Lewis operation by same surgical team in our department from January 2013 to June 2015 were retrospectively analyzed. Patients were divided into three groups according to the width of gastric conduit: width > 5.0 cm as broad group (n=93); width 3.0-5.0 cm as moderate group (n=70); width < 3.0 cm as narrow group (n=119). The gastric conduits of patients in narrow group were completely positioned the esophageal bed and fixed to the pericardium posterior wall. None of patients received pyloroplasty or pylorotomy. Perioperative data, operation associated complications, and postoperative upper gastrointestinal radiographic results(1 week and 4 weeks after operation) were compared among groups. RESULTS: The baseline data among these groups were comparable in terms of age, gender, tumor TNM staging, pathological types, serum albumin level, and the rate of receiving neoadjuvant therapy(all P>0.05). There were no significant differences in operative time, blood loss, and postoperative hospital stay among groups(all P>0.05). No patients died during perioperative peried. Anastomotic leakage occurred in 2 cases, one from broad group and another from narrow group. The incidences of arrhythmia and postoperative pulmonary complications, including infection, atelectasis, pneumothorax, and pleural effusion were similar among groups (all P>0.05). The average amount of gastric juice drainage in narrow group was (98+/-57) ml/day, which was markedly lower than that in broad group [(157+/ 62) ml/day, P=0.000] and in moderate group [(123+/-68) ml/day, P=0.008]. One week after operation, the overall incidence of DGE was 10.6%(30/282), the incidence of DGE in broad, moderate, narrow groups was 17.2%(16/93), 14.3%(10/70), and 3.4%(4/119) respectively, and broad and moderate groups had higher incidence as compared to narrow group (P=0.001 and P=0.006). CONCLUSION: During the Ivor-Lewis operation, application of a narrow gastric conduit (width < 3.0 cm), which completely position the esophageal bed with fixation to the pericardium posterior wall, can significantly reduce the incidence of postoperative early DGE. PMID- 27680063 TI - [Efficacy comparison of Sweet versus Ivor-Lewis esophagectomy in the treatment of middle-lower esophageal squamous cell carcinoma]. AB - OBJECTIVE: To compare the short-term efficacy and long-term survival between Sweet and Ivor-Lewis esophagectomy for patients with middle-lower esophageal squamous cell carcinoma. METHODS: Clinicopathologic data of 1 308 patients with middle-lower esophageal squamous cell carcinoma undergoing Sweet or Ivor-Lewis procedures in our department from January 2007 to December 2014 were retrospectively analyzed, including 1 021 patients of Sweet operation (Sweet group) and 287 patients of Ivor-Lewis operation(Ivor-lewis group). Lymph node clearance, lymphatic metastasis, postoperative complication morbidity and long term survival were compared between the two groups. RESULTS: There were no significant differences in baseline data between the two groups(all P>0.05). There were more lymph nodes resected during the Ivor-Lewis procedure compared with the Sweet procedure (20.8 vs.19.3, P=0.030). Compared with Ivor-Lewis group, the incidence of wound infection in Sweet group was significantly lower[(3.2%(33/1 021) vs. 8.0%(23/287), P=0.000]. Sweet group had a significantly lower rate of delayed gastric emptying[1.9%(19/1 021) vs. 5.2%(15/287), P=0.002] and significantly shorter hospital stay (14.7 days vs. 17.2 days, P=0.029). With respect to other postoperative complications, such as pulmonary complications, cardiac events, anastomotic leakage, vocal cord palsy, chylothorax and pyothorax, the differences between the two groups were not statistically significant. The 5 year survival rate was not significantly different between the two group (54.0% vs. 56.9%, P=0.873). Stratified analysis based on TNM staging showed that no significant difference of 5-year survival rate was found between the two groups in stageI( and stageIII( patients (P>0.05), while the 5-year survival rate of stageII( patients in Sweet group was significantly lower than that in Ivor-Lewis group (56.4%% vs. 70.4%, P=0.039). CONCLUSIONS: For patients with middle-lower esophageal squamous cell carcinoma, Sweet procedure has certain superiority regarding the incidence of wound infection and delayed gastric emptying compared with the Ivor-Lewis procedure. Ivor-Lewis esophagectomy can harvest more lymph nodes. The 5-year survival rate of these two procedures is similar. Sweet procedure is still valuable in clinical practice, especially for stageI( and stageIII( patients, while it requires thorough considerations for stageII( patients. PMID- 27680065 TI - [Efficacy comparison between two-field and three-field lymphadenectomy for thoracic esophageal squamous cell carcinoma]. AB - OBJECTIVE: To compare the safety and efficacy between three-field lymphadenectomy and normative Ivor-Lewis two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma METHODS: Clinical data of 375 patients with thoracic esophageal squamous cell carcinoma who underwent three-field lymphadenectomy(3FL) or Ivor-Lewis two-field lymphadenectomy(2FL, Ivor-Lewis) in Fudan University Shanghai Cancer Center during 2013 were retrieved and collected from electronic medical record system. Ninety-one patients received three-field lymphadenectomy (3FL group), including 16 cases of intra-cervical gastro-esophageal anastomosis and 75 cases of intra-thoracic gastro-esophageal anastomosis, while 284 patients received Ivor-Lewis two-field lymphadenectomy (2FL group) with all intra-thoracic gastro-esophageal anastomosis. Short-term outcomes were compared between two groups, including postoperative anastomotic leakage, pneumonia and respiratory failure, chylothorax, reoperation and 90-day death. Total harvested lymph nodes and positive lymph nodes in each group were also compared. A total of 338 patients were enrolled into survival analysis. Survival curve was presented by Kaplan-Meier method. RESULTS: As compared to 2FL group, the 3FL group had significantly higher ratio of N3 patients [19.8% (18/91) vs. 5.3% (15/284), P=0.000], stageIII( patients [58.2%(53/91) vs. 43.0%(122/284), P=0.007], and upper thoracic cancer patients [12.1%(11/91) vs. 3.5%(10/284), P=0.027]; also the 3FL group had more harvested lymph nodes (40.1+/-14.6 vs. 25.3+/-9.4, P=0.000) and more positive lymph nodes (3.3+/-4.0 vs. 1.7+/-3.2, P=0.000). With respect to pneumonia and respiratory failure, chylothorax, reoperation and 90-day death, no significant differences were found between the group (P=0.447, P=0.751, P=0.678, P=0.685). The 3FL group had a significantly higher incidence of anastomotic leakage than 2FL group [7.7% (7/91) vs. 1.8% (5/284), P=0.011], while its incidence of intrathoracic anastomosis leakage was 4.0% (3/75), which was not significantly different with 1.8%(5/284) of 2FL group (P=0.372). Median follow-up was 33 months. Overall 1-, 2-, 3-year survival rates were 94%, 81% and 70%, while 1-, 2-, 3-year survival rates of 3FL group were 90%, 73% and 66%, of 2FL group were 95%, 84% and 72%, respectively, without significant differences between the two group(P=0.135). Further subgroup analysis showed that no significant differences of postoperative survival in stage I(, II( and III( patients were observed between the two groups (P=0.541, P=0.511, P=0.402), meanwhile no significant differences of postoperative survival in patients with metastasis and without metastasis were found between the two groups as well (P=0.985, P=0.233). CONCLUSIONS: Three-field lymphadenectomy can be performed with acceptable perioperative morbidity and mortality. The prognosis value of three field lymphadenectomy needs further investigation. Patients with thoracic esophageal squamous cell carcinoma may have favorable survival through normative Ivor-Lewis two-field lymphadenectomy. PMID- 27680066 TI - [Short-term outcomes of robot-assisted minimally invasive esophagectomy for esophageal cancer]. AB - OBJECTIVE: To evaluate the feasibility, safety and short-term clinical outcomes of robot-assisted minimally invasive esophagectomy (RAMIE). METHODS: Clinical data of 17 patients with esophageal cancer who received RAMIE between April 2016 and July 2016 were analyzed retrospectively. RESULTS: The age of the patients ranged from 44 to 83. Six patients received neoadjuvant radiochemotherapy while 11 patients underwent surgery alone. All patients were performed by the robot assisted thoraco-laparoscopic minimally invasive esophagectomy. In-hospital mortality was 0%. None was converted to open transthoracic or laparotomy approach. In the neoadjuvant radiochemotherapy group, 3 patients received pathological complete response while 2 patients were stage II(A and 1 patient was stage II(B. In the surgery alone group, 1 patient was stage I(A, 3 patients were stage II(A, 5 patients were stage II(B, 1 patient was stage III(A and 1 patient was stage III(B. The mean operation time was 195 minutes (range 145 to 305 minutes). The mean blood loss was 60 ml (range 30 to 200 ml). Mean lymph node harvest was 28 nodes. The rate of radical resection was 100%. Median ICU stay was 4.5 days (range 1 to 36 days), and median overall postoperative hospital stay was 15.2 days(range 9 to 45 days). Postoperative complication occurred in 4 (23.5%) patients, including 3 (17.6%) of lung lesion, 2 (11.8%) of hoarseness, 1 (5.9%) of chylothorax, while no anastomotic leakage and arrhythmia was observed. CONCLUSION: RAMIE for esophageal cancer is feasible and safe with favorable early outcomes. PMID- 27680067 TI - [Application of mesoesophagus suspension technique in upper mediastinal lymph node dissection during thoracoscopic esophagectomy]. AB - OBJECTIVE: To explore the application of mesoesophagus suspension technique to improve the upper mediastinal lymph node dissection during thoracoscopic esophagectomy in the treatment of esophageal cancer. METHODS: Clinical data of 164 thoracic esophageal cancer patients who underwent combined thoracoscopic and laparoscopic esophagectomy with two-field lymph node dissection in the Union Hospital of Fujian Medical University between October 2012 and June 2015 were retrospectively analyzed. Among 164 patients, 80 cases underwent upper mediastinal lymph node dissection by traditional method (traditional group), and the remaining 84 cases underwent upper mediastinal lymph node dissection by mesoesophagus suspension technique (suspension group). The operation time, estimated blood loss, number of excised lymph nodes and postoperative complications were compared between the two groups. RESULTS: There were no significant differences in gender, age, location of tumor and pathology stage between the two groups. The operation time in the two groups was similar. The suspension group had significantly less thoracic blood loss than traditional group [(85+/-5) ml vs.(140+/-7) ml, P=0.000]. The number of dissected lymph nodes of bilateral recurrent laryngeal nerve was more in suspension group [median (interquartile range): left: 3 (2 to 4) vs. 2 (1 to 3), P=0.013; right: 3(2 to 6) vs. 2(1 to 3), P=0.007]. There was no significant difference in metastatic rate of lymph node in different sites between the two groups. The highest metastatic rate of suspension and traditional group was found at paracardia lymph nodes[22.6%(19/84) and 22.5%(18/80)], the next was at right laryngeal nerve lymph nodes [17.9%(15/84) and 15.0%(12/80)] and left laryngeal nerve lymph nodes [16.7%(14/84) and 12.5%(10/80)]. There were no significant differences with regard to the incidence of major postoperative complications between two groups, including respiratory complication, anastomotic leakage, vocal cord palsy. CONCLUSIONS: Upper mediastinal bilateral recurrent laryngeal nerve lymph node is the predilection site of lymphatic metastasis of thoracic esophageal cancer. Application of mesoesophagus suspension technique in thoracoscopic esophagectomy can improve the clearance quality of bilateral recurrent laryngeal nerve lymph nodes. PMID- 27680068 TI - [Association of postoperative outcome with fasting plasma glucose and risk factors in esophageal squamous cell carcinoma]. AB - OBJECTIVE: To study the impact of preoperative fasting plasma glucose(FPG) on postoperative morbidity and outcome following surgical resection of esophageal squamous cell carcinoma (ESCC), and to analyze the risk factor of postoperative complication in ESCC. METHODS: Clinicopathological data of 314 ESCC patients undergoing esophagectomy in our center between January 2011 and December 2012 were retrospectively collected. Patients were divided into two groups according to their preoperative FBG: normal FPG group (FPG<6.1 mmol/L, 252 cases) and high FBG group (FPG>=6.1 mmol/L, 62 cases, including 14 diabetes cases). Clinicopathological data and postoperative morbidity were analyzed and compared between two groups. Multivariate logistic regression analysis was used to evaluate risk factors for postoperative complications. RESULTS: There were 278 male and 36 female patients with a median age of 59 years (range 42-83 years). As compared to normal FPG group, high FBG group had higher ratio of female [22.6%(14/62) vs. 8.7%(22/252), P=0.000], older median age (66 years vs. 59 years, P=0.010), lower ratio of smoking and alcohol drinking [48.4%(30/62) vs. 73.8%(186/252), 38.7%(24/62) vs. 69.0%(174/252), both P=0.000], higher ratio of comorbid diabetes and hypertension [51.6%(32/62) vs. 15.1%(38/252), 16.1%(10/62) vs. 1.6%(4/252), both P=0.000]. Pathology results showed 206 patients in normal FPG group (81.7%, 206/252) were moderate-poor differentiation, which was obviously lower than 93.5%(58/62) in high FPG group(P=0.023). Patients of two groups completed their operations successfully. Perioperative overall complication morbidity was 24.2%(76/314), and the most common was lung lesions (24 cases of pneumonia, 10 cases of respiratory failure), then was anastomotic leakage (28 cases) and incision infection (18 cases). Differences in overall and other complication morbidity were not significant between two groups (all P>0.05). Multivariate logistic regression analysis revealed that operation time was an independent risk factor of postoperative complications (P=0.047), anastomosis site was an independent risk factor of anastomotic leakage (P=0.036), and FPG was not a risk factor of postoperative complications(respectively, P=0.683, P=0.836, P=0.784, P=0.637). CONCLUSIONS: Preoperative control of FBG does not increase the postoperative complication morbidity. Shortening operation time and choosing appropriate surgical procedure are important to decrease postoperative complications. PMID- 27680069 TI - [Application of bundles of intervention in the treatment of esophageal carcinoma anastomotic leak]. AB - OBJECTIVE: To investigate the application of bundles of intervention in the treatment of esophageal carcinoma anastomotic leak. METHODS: From January 2014 to May 2015, 44 cases of esophageal carcinoma anastomotic fistula were treated by bundles of intervention (through the collection of a series of evidence-based treatment and care measures for the treatment of diseases) in Department of Thoracic Surgery, Huai'an First Hospital, Nanjing Medical University (bundles of intervention group), and 68 patients with esophageal carcinoma postoperative anastomotic leak from December 2013 to January 2012 receiving traditional therapy were selected as the control group. The clinical and nutritional indexes of both groups were compared. RESULTS: There were no significant differences in general data and proportion of anastomotic leak between the two groups. Eleven patients died during hospital stay, including 3 cases in bundles of intervention group(6.8%) and 8 cases in control group (11.8%) without significant difference(P = 0.390). In bundles of intervention group, 1 case died of type III( intrathoracic anastomotic leak, 2 died of type IIII( intrathoracic anastomotic leak. In control group, 2 cases died of type III( cervical anastomotic leak, 2 died of type III( intrathoracic anastomotic leak and 4 of type IIII( intrathoracic anastomotic leak. The mortality of bundles of intervention group was lower than that of control group. The duration of moderate fever [(4.1+/-2.4) days vs. (8.3+/-4.4) days, t=6.171, P=0.001], the time of antibiotic use [(8.2+/ 3.8) days vs.(12.8+/-5.2) days, t=5.134, P = 0.001], the healing time [(21.5+/ 12.7) days vs.(32.2+/-15.8) days, t=3.610, P=0.001] were shorter, and the average hospitalization expenses[(63+/-12) thousand yuan vs. (74+/-19) thansand yuan, t=3.564, P=0.001] was lower in bundles of intervention group than those in control group. Forty-eight hours after occurrence of anastomotic leak, the levels of hemoglobin, albumin and prealbumin were similar in both groups. However, at the time of fistula healing, the levels of hemoglobin [(110.6+/-10.5) g/L vs.(103.8+/-11.1) g/L, t=3.090, P=0.002], albumin [(39.2+/-5.2) g/L vs.(36.3+/ 5.9) g/L, t=2.543, P=0.013] and prealbumin [(129.3+/-61.9) g/L vs.(94.1+/-66.4) g/L, t=2.688, P=0.008] were significantly higher in bundles of intervention group. CONCLUSION: In the treatment of postoperative esophageal carcinoma anastomotic leak, application of bundles of intervention concept can significantly improve the nutritional status and improve the clinical outcomes. PMID- 27680070 TI - [Efficacy comparison of laparoscopic Nissen, Toupet and Dor fundoplication in the treatment of hiatal hernia complicated with gastroesophageal reflux disease]. AB - OBJECTIVE: To compare the efficacy and safety among laparoscopic Nissen, Toupet and Dor fundoplication in the treatment of hiatal hernia complicated with gastroesophageal reflux disease (GERD). METHODS: Clinical data of 276 patients of hiatal hernia complicated with GERD undergoing operation in our hospital from December 2012 to January 2015 were retrospectively analyzed, including 149 patients of laparoscopic Nissen fundoplication (Nissen group), 41 of laparoscopic Toupet fundoplication (Toupet group), and 86 patients of laparoscopic Dor fundoplication (Dor group). Esophageal reflux status, esophageal manometry, GERD Q rating scale, and postoperative recovery were compare among the three groups. RESULTS: Reflux status was improved significantly in the three groups after operation(all P<0.05),except that the efficacy in reducing reflux episodes and reflux longest time was not obvious in Toupet group(P>0.05). There were no significant differences in postoperative reflux time, acid reflux time ratio, reflux longest time ratio, DeMeester score among the three groups (all P>0.05). Pairwise comparison showed that Dor group was significantly better than Toupet group in reducing the number of reflux episode(14.36+/-10.58 vs. 29.83+/-19.71) and long-reflux (0.64+/-0.21 vs. 6.20+/-3.48)(both P<0.05), but Nissen group was better than these two groups in reducing the number of long-reflux (0.38+/-0.16, P<0.05). As compared to pre-operation, the postoperative esophageal sphincter pressure and residual pressure increased significantly, and the relaxation rate reduced significantly (all P<0.05), while the episode of ineffective swallowing increased significantly in Toupet group (11.25+/-2.04 vs. 6.36+/-3.26, P<0.05). The contrast in esophageal manometry between Toupet and Dor group showed that Dor group was better than Toupet group in the recovery of lower esophageal sphincter pressure (mean resting breathing) [(20.69+/-13.95) mmHg vs.(12.91+/-6.89) mmHg] and the decrease of ineffective swallowing [9.15+/-6.44 vs. 11.25+/-2.04](both P<0.05), while such results of Dor group were similar to Nissen group[(19.87+/ 10.40) mmHg, 6.15+/-2.95, all P>0.05]. The GERD Q scores were significantly decreased after operation in 3 groups(Nissen group:10.94+/-2.20 vs.7.41+/-1.43, t=11.667, P=0.001; Toupet group: 10.91+/-2.02 vs.7.18+/-1.33, t=5.109, P=0.005; Dor group: 10.69+/-1.69 vs. 7.10+/-1.30, t=7.610, P=0.002). There was no significant difference in GERD Q scores among three groups (F=1.465, P=0.207). The operative time, blood loss, hospital stay and complications were not significantly different among 3 groups (all P>0.05). Follow-up period was 12-51 months (median 19 months), and no significant difference in recurrence was found [Nissen group: 2 cases (1.3%), Toupet group: 1 case (2.4%), Dor group: 1 case (1.2%), chi2=0.363, P=0.834]. CONCLUSIONS: It is safe and feasible for these three laparoscopic fundoplications to the treatment of hiatal hernia complicated with GERD. But laparoscopic Nissen and Dor fundoplication are better than Toupet fundoplication in reducing the number of reflux episodes, suppressing long reflux, increasing lower esophageal sphincter pressure (mean resting respiration) and decreasing the incidence of postoperative dysphagia. PMID- 27680071 TI - [Application of gastroepiploic tunnel esophagogastrostomy in minimally invasive esophagectomy]. AB - OBJECTIVE: To explore the clinical efficacy and safety of gastroepiploic tunnel esophagogastrostomy applied in minimally invasive esophagectomy and gastroesophageal cervical anastomosis. METHODS: Clinical data of 137 esophageal cancer patients who received minimally invasive esophagectomy from December 2013 to June 2015 in Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University were analyzed retrospectively, including 84 patients receiving anastomosis with tubular anastomat (circular staple group), and 53 patients receiving gastroepiploic tunnel anastomosis(tunnel group, position of tunnel anastomosis located in the side of gastrocolic omentum, about 2-3 cm apart from fundus). Incidence of postoperative anastomotic leakage and stricture was compared between two groups. RESULTS: All the 137 patients completed minimally invasive esophageal surgeries successfully without conversion to open thoracic or abdominal operation. The time for anastomosis was(20.2+/-3.1) minutes in circular stapler group and (38.9+/-2.9) minutes in tunnel group respectively, and the difference was statistically significant (t=75.22, P=0.000 0). The incidence of postoperative anastomotic leakage was 21.4%(18/84) in circular stapler group and 0(0/53) in tunnel group respectively, and the difference was statistically significant (P=0.000 3). All the patients were followed up for more than 6 months. During follow-up period, the incidence of postoperative anastomotic stricture was 14.3%(12/84) in circular stapler group and 3.8%(2/53) in tunnel group respectively, and the difference was statistically significant(P=0.047 9). CONCLUSION: The gastroepiploic cervical tunnel anastomosis is safe and effective and can reduce the incidence of postoperative anastomotic leakage as well as anastomotic stricture. PMID- 27680072 TI - [Preliminary investigation of intramural lateral spread distance in pull-through conformal resection of low rectal cancer]. AB - OBJECTIVE: To investigate the intramural lateral spread distance in low rectal cancer in order to provide basis for safety lateral resection margin of pull through conformal resection (PTCR). METHODS: The patients with low rectal cancer who received low anterior resection or abdominal-perineal resection in Changhai Hospital from December 2015 to March 2016 were enrolled and Surgical specimens were collected. After the specimens were fixed in 10% formaldehyde for 24 hours, a piece of tissue that was 1.5 cm in length and 0.5 cm in width from the edge of tumor was cut. The tissue was obtained in the direction of 3, 5, 7 and 9 o'clock clockwise. The distance of intramural lateral spread was measured in the specimens and the risk factors were analyzed. RESULTS: A total of 83 specimens were collected and the overall proportion of intramural lateral spread was 71.1%(59/83). The rate of lateral spread from 3 to 9 o'clock was 34.9%(29/83), 26.5%(22/83), 32.5%(27/83) and 37.3%(31/83) respectively, and the difference was not statistically significant(chi2=2.444 9, P=0.485 3). The median distance of lateral spread in each direction was all 0 mm and the quartile range was 1 mm, 0.5 mm, 0.55 mm and 1 mm respectively. The 5th percentile (P5) of each direction was all 0 mm and the 95th percentile(P95) of each direction was 2.5 mm, 1.6 mm, 2.6 mm, 2.5 mm, respectively and the difference was not statistically significant either(chi2=5.331 0, P=0.148 9). The rate of lateral spread of T1, T2, T3 and T4 was 0/4, 58.3%(14/24), 83.0%(44/53) and 1/2 respectively, and there was significant difference(P=0.005 0). The multivariate analysis indicated that T stage (P=0.002 2, OR=3.741, 95% CI: 1.606-8.716) was the risk factor of intramural lateral spread. CONCLUSIONS: The intramural lateral spread does exist in low rectal cancer and T stage is the risk factor of lateral spread. The lateral resection margin should be 5 mm from the tumor edge at least when PTCR is performed. PMID- 27680073 TI - [Applicability and indications of colonoscopic screening for Crohn's disease in patients with fistula-in-ano]. AB - OBJECTIVE: To determine the indications of colonoscopic screening for Crohn's disease in patients with fistula-in-ano. METHODS: Clinical data of 302 patients with perianal fistula who received colonoscopy examination from January 2010 to December 2013 in the Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University were analyzed retrospectively. Parameters for differentiating perianal Crohn's disease from nonspecific fistulae were screened by logistic regression analysis. A regression mathematical model was established for the prediction of perianal Crohn's disease. RESULTS: A total of 302 patients received colonoscopy examination, and Crohn's disease was found in 16 patients (CD group). Results of univariate analysis on 26 parameters of clinical manifestation, laboratory and radiological examination revealed that differences in 11 clinical parameters between the CD group and non-CD group were statistically significant(all P<0.05), including age, BMI, abdominal pain, non specific symptoms, multiple fistula, complex anal fistula, neutrophil count, platelet count, activated partial thromboplastin time, hemoglobin concentration and serum albumin concentration. Multivariate analysis revealed that age<=40 years (OR=14.464, 95% CI: 1.143-183.053, P=0.039), BMI<24.0 kg/m2 (OR=8.220, 95% CI:1.005-67.200, P=0.049), abdominal pain (OR=13.148, 95% CI: 1.110-155.774, P=0.041), complex anal fistula (OR=7.056, 95% CI:1.166-42.688, P=0.033) and elevated platelet count (OR=1.012, 95% CI: 1.004-1.0194, P=0.003) were independent risk factors for discovery of Crohn's disease by colonoscopy. Area under the ROC curve of the regression mathematical model based on factors mentioned above was 0.921, indicating that the model was highly predictive. The sensitivity and specificity of this model was 81.3% and 86.7% respectively when the optimal diagnostic cut-off point was established at 0.856. CONCLUSIONS: Parameters that predict Crohn's disease in patients with perianal fistula include age, BMI, abdominal pain, classification of fistula and platelet count. Colonoscopy is recommended for patients at high risk. PMID- 27680074 TI - [Comparative analysis of postoperative complications on elderly colorectal cancer patients over 65 years with and without comorbid cardiovascular diseases]. AB - OBJECTIVE: To investigate the risk of postoperative complications in elderly colorectal cancer patients over 65 years with comorbid cardiovascular diseases. METHODS: A total of 381 elderly colorectal cancer patients over 65 years were pathologically diagnosed as colorectal adenocarcinoma and underwent the first surgery in Beijing Hospital during January 2013 and December 2014. Patients were divided into comorbid cardiovascular disease group (258 cases) and non cardiovascular disease group (123 cases) according to the existence of comorbid cardiovascular disease. The morbidity of postoperative complication was compared between two groups. RESULTS: There was no significant difference in the morbidity of postoperative complication between two groups [27.9%(72/258) vs. 29.3%(36/123), P>0.05]. According to the Clavien-Dindo classification of postoperative complications, the morbidities of complication at all levels between two groups were not significantly different(all P>0.05). But in terms of cardiovascular complications, the morbidity of comorbid cardiovascular disease group was significantly higher than that of non-cardiovascular disease group [7.4%(19/258) vs. 0.8%(1/123), chi2=6.678, P=0.010], while no significant differences in pulmonary and abdominal complications were found between two groups(all P>0.05). The morbidities of other complications (deep vein thrombosis, urinary tract infection and renal complications, etc.) of comorbid cardiovascular disease group were lower than those in non-cardiovascular disease group [2.7%(7/258) vs. 8.1%(10/123), chi2=5.733, P=0.017]. Different types of cardiovascular diseases, different levels of cardiac risk index and American Society of Anesthesiologists(ASA) rating were not significantly related to the patient's occurrence of postoperative complications(all P>0.05). CONCLUSIONS: Surgery treatment for elderly colorectal cancer patients over 65 years with comorbid cardiovascular diseases is safe. However, strict cardiovascular monitoring should be performed and necessary measures should be carried out in time. PMID- 27680075 TI - [Assessment of the risk factors relating to lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy and the clinical significance]. AB - OBJECTIVE: To identify the risk factors associated with lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy (CRT). METHODS: From January 2005 to December 2013, the clinical data of 178 patients with advanced rectal cancer undergoing radical excision after neoadjuvant CRT in our department were reviewed retrospectively. A total of 11 clinicopathologic factors relating to lymph node metastasis were studied using univariate and multivariate Logistic regression analyses. RESULTS: There were 74(41.6%) cases with lymph node metastasis, while 104 cases without lymph node metastasis. Univariate analysis showed that age(P=0.000 2), post-CRT CEA level(P=0.011 2), ypT stage(P=0.000 0), pathologic type(P=0.004 0), and tumor regression grade(TRG)(P=0.033 8) were significantly associated with lymph node metastasis. Multivariate analysis showed that age(OR=2.385, 95% CI:1.372 ~ 4.147, P=0.002 1), post-CRT CEA level(OR=2.310, 95% CI:1.005 ~ 5.307, P=0.048 6) and ypT stage(OR=2.592, 95% CI:1.236 ~ 5.432, P=0.011 7) were independent risk factors. However, 15.8% of the patients who achieved TRG1 had lymph node metastasis and TRG failed to independently correlate with lymph node metastasis in rectal cancer after neoadjuvant CRT. CONCLUSIONS: There was a higher ratio of lymph node metastasis in rectal cancer patients who were young, CEA>=5 MUg/L or deep invasion after neoadjuvant CRT. Therefore, neoadjuvant CRT should be carefully considered in these patients. PMID- 27680076 TI - [Application study on regional infusion chemotherapy by celiac trunk during operation in advanced gastric cancer patients]. AB - OBJECTIVE: To explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients. METHODS: One hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups. RESULTS: The baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9+/-14.8) hours vs. (68.9+/-15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1+/-17.1) ml vs.(61.9+/-18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), chi2=0.256, P=0.613], and the long term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), chi2=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, chi2=5.382, P=0.020; 58.4% vs. 34.4%, chi2=6.636, P=0.010). CONCLUSION: Regional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate. PMID- 27680077 TI - [Preliminary exploration on accurately preoperative evaluation of colonic lesions in slow transit constipation complicated with adult megacolon]. AB - OBJECTIVE: To investigate the application value of colonic transit test (CTT) combined with anorectal manometry (ARM), barium enema (BE) and defecography (DFG) in accurately evaluating colonic lesions of slow transit constipation complicated with adult megacolon. METHODS: Clinical data of 47 above patients admitted between October 2007 and February 2015 in the People's Hospital of Hunan Province were analyzed retrospectively. All the patients were examined with>=2 times of CTT combined with ARM and BE, and 42 cases received additional DFG at the same time, to evaluate colonic lesions before operation. Operative biopsy pathology was used as the standard. The sensitivity, specificity, positive predictive value(PPV) and negative predictive value(NPV) of positioning in the ascending colon and caecum, transverse colon and descending colon were calculated, and the consistency was represented by Kappa test(Kappa value>=0.75 indicates good consistency, meanwhile higher Kappa value indicates better consistency). The Heikkinen score was used to evaluate defecation function at postoperative 6 months. RESULTS: The age of 47 patients was from 18 to 56 years old. Compared with intraoperative findings and biopsy pathology, the diagnostic coincidence rate was 89.4% by CTT combined with BE and DFG positioning, which suggested pathology-changed colonic segment locating in the ascending colon and cecum (n=12), transverse colon (n=26) and descending colon (n=9), while intraoperative findings and biopsy pathology suggested pathology-changed colonic segment locating in the ascending colon and cecum (n=11), transverse colon (n=23) and descending colon (n=13). The sensitivity was 88.3%, specificity 93.5%, PPV 92.1%, NPV 94.9% and Kappa value was 0.827(P<0.001). Procedures performed included segmental colectomy (n=8), subtotal colectomy (n=29), total colectomy (n=10). There was no serious complication during and after operation. Defecatory function was excellent in 24 cases (60.0%), good in 10 (25.0%), and moderate in 6 (15.0%) evaluated by Heikkinen score at postoperative 6 months. A total of 40 patients were followed up from 1 to 7 years (median 3 years) and there was no long-term diarrhea and recurrence of constipation or giant colon after operation. CONCLUSION: Preoperative detection of CTT combined with ARM, BE and DFG in patients with slow transit constipation complicated with adult megacolon can make a more precise assessment of the extent of colonic lesions in advance, which has a good clinical predictive value. PMID- 27680078 TI - [Selection of surgical approaches and lymph node dissection in the esophageal cancer patients]. AB - According to the different surgical approaches and its corresponding lymph node dissection modes, surgical treatment for esophageal cancer can be divided into different surgical treatment modes. Currently in China, the surgical treatment modes for esophageal cancer including left and right thoracic approaches and its corresponding lymph node dissection modes (two-field or three-field) are widely practiced. Different surgical approaches may influence lymph node dissection results, and it may eventually affect the survival of the esophageal cancer patients, therefore, individual selection of appropriate surgical approaches and lymph node dissection extent for esophageal cancer patients based on precise preoperative examinations and clinical stages is very important. By summarizing the recent domestic and foreign research results, it demonstrates that 2-field lymph node dissection by right approach is more radical than left approach, 3 field lymph node dissection by right approach is more radical than 2-field right approach, and may eventually improve the prognosis of patients. However, most of them are retrospective studies which need large sample randomized controlled trials support. This article reviews and summarizes recently published literatures, and discuss the selection of surgical approach and the extent of lymph node dissection for esophageal cancer from three aspects that the effect of left and right thoracic approach on lymph node dissection and prognosis, how to choose individual surgical approach by different position and stage, and what kind of patients need right thoracic approaches with 3-field lymph node dissection. PMID- 27680079 TI - [Research progress in molecular classification of gastric cancer]. AB - Gastric cancer(GC) is a highly heterogeneous malignancy. The present widely used histopathological classifications have gradually failed to meet the needs of individualized diagnosis and treatment. Development of technologies such as microarray and next-generation sequencing (NGS) has allowed GC to be studied at the molecular level. Mechanisms about tumorigenesis and progression of GC can be elucidated in the aspects of gene mutations, chromosomal alterations, transcriptional and epigenetic changes, on the basis of which GC can be divided into several subtypes. The classifications of Tan's, Lei's, TCGA and ACRG are relatively comprehensive. Especially the TCGA and ACRG classifications have large sample size and abundant molecular profiling data, thus, the genomic characteristics of GC can be depicted more accurately. However, significant differences between both classifications still exist so that they cannot be substituted for each other. So far there is no widely accepted molecular classification of GC. Compared with TCGA classification, ACRG system may have more clinical significance in Chinese GC patients since the samples are mostly from Asian population and show better association with prognosis. The molecular classification of GC may provide the theoretical and experimental basis for early diagnosis, therapeutic efficacy prediction and treatment stratification while their clinical application is still limited. Future work should involve the application of molecular classifications in the clinical settings for improving the medical management of GC. PMID- 27680080 TI - [Detection and clinical significance of circulating tumor cells in gastric cancer]. AB - The death of patients with gastric cancer is mainly due to its recurrence and metastasis, and circulating tumor cell (CTC) is the necessary condition of metastasis. As liquid biopsy, CTC detection has its certain clinical significance. The detection is required after enrichment because circulating tumor cells are rare. Many enrichment methods have been developed: methods based on physical characteristics of TCT, like density, size and dielectric properties and so on; immunogenicity, like Cell Search System; and microfluidic chip technology. The immunofluorescence is commonly used to identify CTC in gastric cancer and the isolated CTC can also be used for the following analysis on the level of nucleic acid, protein and gene regulation. Detection of CTC in gastric cancer is helpful to judge the prognosis, assess staging, monitor the curative effect and guide the development of drug. There are many challenges for clinical transformation of CTC: the lower enrichment efficiency, the less specific surface markers, the uncertain diagnostic efficiency and so on, but it also has the good research prospect because it is non-invasive, repeatable and can real-time monitor the condition and guide the clinical treatment compared with pathological biopsy. In this paper, the detection and identification methods, and clinical value of CTC in gastric cancer patients are reviewed. PMID- 27680081 TI - Commentary: Dennis D. Drotar Distinguished Research Award: Academic and Personal Reflections on Childhood Cancer Research Across the Illness Spectrum. PMID- 27680082 TI - Peer Victimization in Adolescents With Severe Obesity: The Roles of Self-Worth and Social Support in Associations With Psychosocial Adjustment. AB - Objective: To examine the associations of peer victimization with internalizing symptoms, externalizing symptoms, social competence, and academic performance in a clinical sample of adolescents with severe obesity, and whether self-worth and social support affect these associations. Methods: Multisite cross-sectional data from 139 adolescents before weight loss surgery ( M age = 16.9; 79.9% female, 66.2% White; M Body Mass Index [BMI] = 51.5 kg/m 2 ) and 83 nonsurgical comparisons ( M age = 16.1; 81.9% female, 54.2% White; M BMI = 46.9 kg/m 2 ) were collected using self-reports with standardized measures. Results: As a group, participants did not report high levels of victimization. Self-worth mediated the effects of victimization on a majority of measures of adjustment, and further analyses provided evidence of the buffering effect of social support for some mediational models. Conclusions: Self-worth and social support are important targets for prevention and intervention for both victimization and poor adjustment in adolescent severe obesity. PMID- 27680083 TI - Early Alterations in Bone Characteristics of Type I Diabetic Rat Femur: A Fourier Transform Infrared (FT-IR) Imaging Study. AB - Alterations in microstructure and mineral features can affect the mechanical and chemical properties of bones and their capacity to resist mechanical forces. Controversial results on diabetic bone mineral content have been reported and little is known about the structural alterations in collagen, maturation of apatite crystals, and carbonate content in diabetic bone. This current study is the first to report the mineral and organic properties of cortical, trabecular, and growth plate regions of diabetic rat femurs using Fourier transform infrared (FT-IR) microspectroscopy and the Vickers microhardness test. Femurs of type I diabetic rats were embedded into polymethylmethacrylate blocks, which were used for FT-IR imaging and microhardness studies. A lower mineral content and microhardness, a higher carbonate content especially labile type carbonate content, and an increase in size and maturation of hydroxyapatite crystals were observed in diabetic femurs, which indicate that diabetes has detrimental effects on bone just like osteoporosis. There was a decrease in the level of collagen maturity in diabetic femurs, implying a decrease in bone collagen quality that may contribute to the decrease in tensile strength and bone fragility. Taken together, the findings revealed alterations in structure and composition of mineral and matrix components, and an altered quality and mechanical strength of rat femurs in an early stage of type I diabetes. The results contribute to the knowledge of structure-function relationship of mineral and matrix components in diabetic bone disorder and can further be used for diagnostic or therapeutic purposes. PMID- 27680084 TI - Study of the AlS4Pc-Polylysine Ion Pair, a Red-Fluorescent Probe: Its High Specificity, Large Concentration Range Response to Bismuth Ion, and Application. AB - Tetrasulfonated aluminum phthalocyanine (AlS4Pc), a strongly red-emitting compound, shows high detection sensitivity, little effect of photobleaching, and photochemical stability, making it an excellent red-fluorescent probe. We have observed that in acid media, a low concentration of poly-L-lysine (PLL) has a strong fluorescence-quenching effect on AlS4Pc, forming the ion-pair complex as AlS4Pc-PLL with almost no fluorescence. However, in the presence of Bi3+, the fluorescence of AlS4Pc-PLL dramatically recovers and the emission is visual because of the remarkable recovery. Screening experiments with other metal ions reveal that only Bi3+ can restore the fluorescence of the AlS4Pc-PLL complex. The presence of other metal ions does not result in the recovery of fluorescence, indicating the high specificity of the response to Bi3+ of AlS4Pc-PLL. This is the key finding of the present study. It was also observed that the response to Bi3+ of AlS4Pc-PLL exhibits a linear relationship over a large concentration range (three orders of magnitude). Based on these findings, we have established a new quantitative analysis method for Bi3+ with high specificity and high sensitivity, using the ion-pair AlS4Pc-PLL complex as a red-fluorescent probe, and we discuss the reaction mechanism. The detection limit of this method is 0.0021 mg L-1 The linear relationship applies to the range of 0.007-34.9 mg L-1 with a correlation coefficient of 0.9993. The method established addresses the complex operation and time-consuming problems in traditional methods and is thus suitable for real applications. Satisfactory results have been obtained when the method was applied to the measurement of real samples. This study further expands the scope of new applications of phthalocyanine-based red-fluorescent probes in analytical sciences. PMID- 27680085 TI - Fourier Transform Infrared (FT-IR) Spectroscopic Imaging Analysis of Partially Miscible PMMA-PEG Blends Using Two-Dimensional Disrelation Mapping. AB - A novel technique called disrelation spectroscopic imaging describes the process of identifying an area where a coordinated or out-of-phase change in pattern of spectral absorbance occurs. Disrelation mapping can be viewed as a spatial filter based on the well-established two-dimensional (2D) correlation function to highlight specific areas where disrelated variation occurs between nu1 and nu2. Disrelation intensity develops only if the spectral absorbance measured at nu1 and nu2 vary out of phase with each other within a specific spatial area. The disrelation mapping locates regions where absorbance varies in a dissimilar manner because of the contribution from species of different physical or chemical origins. Consequently, it becomes possible to probe onset of molecular interactions or presence of intermediate forms between components, which is not fully detected by the conventional visualizations based on a single wavenumber. Data analysis using disrelation mapping applied to Fourier transform infrared (FT IR) spectroscopic images is presented in this study. Data sets of FT-IR spectroscopic images of blends of poly(methyl methacrylate) (PMMA) and polyethylene glycol (PEG) were subjected to the disrelation mapping. It was found that the disrelation intensity between 1730 and 1714 cm-1 becomes especially acute around the spatial boundary between PMMA and PEG domains within the studied blend sample. Thus the band at 1730 cm-1 most likely represents the C=O stretching mode of the C=O...H-O species due to the intermolecular hydrogen bonding between PMMA and PEG. The appearance of such disrelation is more noticeable in the PEG-rich region, for the PEG with low molecular weight. Consequently, it suggests that the blends of PMMA and PEG are partially miscible at the molecular level and these intermolecular interactions are affected by the quantity of the terminal -OH groups of the PEG. PMID- 27680086 TI - Use of Gradient Dilution to Detect and Correct Matrix Interferences in Inductively Coupled Plasma-Time-of-Flight Mass Spectrometry (ICP-TOFMS). AB - Our research group earlier used dispersion that occurs during flow injection to detect and reduce matrix interference in inductively coupled plasma-time-of flight mass spectrometry (ICP-TOFMS). In the absence of a matrix interference, the ratio of signals from any two sample constituents should remain constant, independent of the dilution, over the course of a flow-injection transient. However, when an interferent is present, the signal ratio from different analytes will change with dilution, owing to the difference in severity of the interference on specific analytes. As a result, matrix interference can be recognized (flagged) by monitoring the signal ratios of two analytes over the course of a flow-injection transient; a ratio that changes over time indicates the presence of an interferent. The drawback of this earlier method was that dispersion, and therefore dilution, was somewhat element-specific, causing the ratios to wander even when no interference existed. Here, a gradient HPLC pump is used to overcome this drawback by creating a longer, better-controlled dilution. Under these conditions, variation in dispersion between elements is negligible and difficulties associated with it are reduced or eliminated. Further, when an interference exists, the optimal dilution factor to reduce the interference to an acceptable level can be found from the gradient-dilution curve as the point where the signal ratio between two elements becomes constant. PMID- 27680088 TI - To Change is Human: "Abnormal" Reliable Change Memory Scores are Common in Healthy Adults and Older Adults. AB - OBJECTIVE: The rate at which people obtain reliably improved or declined cognitive test scores when retested, in the absence of a change in clinical condition, is largely unknown. The purpose of this study was to illustrate the prevalence of statistically reliable change scores on memory test batteries in healthy adults and older adults. METHOD: Participants included three adult and older adult test-retest samples from memory test batteries. Reliable change scores (reliable change index with 90% confidence interval and practice effects) were calculated for the indexes and subtests of each battery. Multivariate analyses involved calculating the frequencies of healthy people obtaining one or more reliably declined or one or more reliably improved scores when considering all change scores simultaneously within each battery. RESULTS: Across all batteries, having one or more reliably changed index or subtest score on retest was common. With most batteries, having two or more reliably changed scores was uncommon. Those with higher intellectual abilities were more likely to have a change on retest; however, no significant differences in base rates were found based on education level, sex, or ethnic minority status. Those older adults who did not have any low memory scores were more likely to improve than decline on retest. CONCLUSIONS: Having a single reliably changed score on retest is common when interpreting a battery of memory measures. This has implications for determining cognitive decline and cognitive recovery, suggesting that multivariate interpretation is necessary. PMID- 27680087 TI - Memory Binding Test Distinguishes Amnestic Mild Cognitive Impairment and Dementia from Cognitively Normal Elderly. AB - OBJECTIVE: We aimed to assess reliability and cross-sectional discriminative validity of the Memory Binding Test (MBT) to distinguish persons with amnestic cognitive impairment (aMCI) and dementia from cognitively normal elderly controls. METHOD: The MBT was administered to 20 participants with dementia, 31 with aMCI and 246 controls, who received the first administration of the MBT from May 2003 to December 2007, as a substudy of the community-based Einstein Aging Study (age range: 70+). The optimal index resulted from comparing the partial area under the receiver operating characteristic curves (ROC AUC) of four major MBT indices for specificities >=0.70. Optimal cut-score of the optimal index was selected by maximizing the sum of sensitivity and specificity. Age and education effects were assessed using stratified cut-scores and adjusted logistic regression. Reliability was computed as intraclass correlation between scores at baseline and 1-year follow-up for participants who remained cognitively normal. RESULTS: Total number of Items recalled in the Paired condition (TIP) was elected the optimal index. TIP cut-score was <=22 for differentiating aMCI alone (sensitivity = 0.74, specificity = 0.73) and aMCI and dementia combined (sensitivity = 0.84, specificity = 0.73) from controls. It was <=17 for differentiating dementia from aMCI and controls (sensitivity = 0.95, specificity = 0.87). Age and education adjustments did not materially improve discriminative validity. The reliability of TIP was 0.77. CONCLUSIONS: MBT achieved moderate to good reliability. TIP had superior cross-sectional discriminative validity than the other MBT indices. We recommend using the empirical cut-score of TIP <=22 for discriminating aMCI and dementia and <=17 for discriminating dementia alone. PMID- 27680089 TI - Decision-making in Cognitively Unimpaired Illiterate and Low-educated Older Women: Results on the Iowa Gambling Task. AB - OBJECTIVE: This study investigated the pattern of decision-making (DM) on the Iowa Gambling Task (IGT) in a sample of Portuguese speaking healthy older women in Brazil with limited education: illiterate, 1-2 years, and 3-4 years of schooling. METHODS: Around 164 non-demented community-dwelling women participated in the study. Among them 60 were illiterate, 52 had 1-2 years of schooling and 52 had 3-4 years of schooling. Participants completed the instruments: Brief Cognitive Screening Battery (BCSB), Mini-Mental State Examination, Verbal Fluency Test (animal category), Clock Drawing Test, Geriatric Depression Scale, Geriatric Anxiety Inventory, Digit Span Forward and Backward, Raven's Coloured Progressive Matrices, Wisconsin Card Sorting Test, and IGT. RESULTS: The three education groups were equivalent as to age, number of diseases, medications taken daily, depression, and anxiety symptoms. In the IGT the literate older adults made more advantageous choices than the illiterate and IGT performance improved linearly with higher levels of education. IGT performance correlated significantly with all cognitive test scores with the exception of the memorization of the pictures on the BCSB. CONCLUSION: The results suggested that education influences IGT performance, with worse scores among the illiterate. Results may be used by clinicians to interpret IGT performance among seniors with low literacy levels. PMID- 27680090 TI - The axoneme, a biological template to design a swell energy recovery system. AB - The axonemal micro-machinery, the axial skeleton and actuator of cilia and flagella of eukaryotic cells, is able to bend and twist and generates wave trains. We already demonstrated that it can be the template to construct an active trunk robot (Cibert 2013 Bioinspir. Biomim. 8 026006). The work presented in this paper describes how the axonemal model can also be useful to design worm shaped devices to convert swell energy into usable energy such as electricity. Using dynamic simulation we have designed three models either very close to the biological machinery or being a reasonable interpretation of its functioning principles. Their main advantage as compared with another existing device, Pelamis, is the additional twist degree-of-freedom that gives interesting properties to the system. PMID- 27680092 TI - A 2S Albumin from the Seed Cake of Ricinus communis Inhibits Trypsin and Has Strong Antibacterial Activity against Human Pathogenic Bacteria. AB - Hospital-acquired infections caused by antibiotic-resistant bacteria threaten the lives of many citizens all over the world. Discovery of new agents to hinder bacterial development would have a significant impact on the treatment of infections. Here, the purification and characterization of Rc-2S-Alb, a protein that belongs to the 2S albumin family, from Ricinus communis seed cake, are reported. Rc-2S-Alb was purified after protein extraction with Tris-HCl buffer, pH 7.5, fractionation by ammonium sulfate (50-75%), and chromatography on Phenyl Sepharose and DEAE-Sepharose. Rc-2S-Alb, a 75 kDa peptide, displays trypsin inhibitory activity and has high in vitro antibacterial activity against Bacillus subtilis, Klebsiella pneumonia, and Pseudomonas aeruginosa, which are important human pathogenic bacteria. Atomic force microscopy studies indicated that Rc-2S Alb disrupts the bacterial membrane with loss of the cytoplasm content and ultimately bacterial death. Therefore, Rc-2S-Alb is a powerful candidate for the development of an alternative drug that may help reduce hospital-acquired infections. PMID- 27680091 TI - Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries. AB - BACKGROUND: The aim of this ecological study was to identify the main nutritional factors related to the prevalence of cardiovascular diseases (CVDs) in Europe, based on a comparison of international statistics. DESIGN: The mean consumption of 62 food items from the FAOSTAT database (1993-2008) was compared with the actual statistics of five CVD indicators in 42 European countries. Several other exogenous factors (health expenditure, smoking, body mass index) and the historical stability of results were also examined. RESULTS: We found exceptionally strong relationships between some of the examined factors, the highest being a correlation between raised cholesterol in men and the combined consumption of animal fat and animal protein (r=0.92, p<0.001). The most significant dietary correlate of low CVD risk was high total fat and animal protein consumption. Additional statistical analyses further highlighted citrus fruits, high-fat dairy (cheese) and tree nuts. Among other non-dietary factors, health expenditure showed by far the highest correlation coefficients. The major correlate of high CVD risk was the proportion of energy from carbohydrates and alcohol, or from potato and cereal carbohydrates. Similar patterns were observed between food consumption and CVD statistics from the period 1980-2000, which shows that these relationships are stable over time. However, we found striking discrepancies in men's CVD statistics from 1980 and 1990, which can probably explain the origin of the 'saturated fat hypothesis' that influenced public health policies in the following decades. CONCLUSION: Our results do not support the association between CVDs and saturated fat, which is still contained in official dietary guidelines. Instead, they agree with data accumulated from recent studies that link CVD risk with the high glycaemic index/load of carbohydrate-based diets. In the absence of any scientific evidence connecting saturated fat with CVDs, these findings show that current dietary recommendations regarding CVDs should be seriously reconsidered. PMID- 27680093 TI - Heterogeneously Catalyzed Hydrothermal Processing of C5-C6 Sugars. AB - Biomass has been long exploited as an anthropogenic energy source; however, the 21st century challenges of energy security and climate change are driving resurgence in its utilization both as a renewable alternative to fossil fuels and as a sustainable carbon feedstock for chemicals production. Deconstruction of cellulose and hemicellulose carbohydrate polymers into their constituent C5 and C6 sugars, and subsequent heterogeneously catalyzed transformations, offer the promise of unlocking diverse oxygenates such as furfural, 5 hydroxymethylfurfural, xylitol, sorbitol, mannitol, and gluconic acid as biorefinery platform chemicals. Here, we review recent advances in the design and development of catalysts and processes for C5-C6 sugar reforming into chemical intermediates and products, and highlight the challenges of aqueous phase operation and catalyst evaluation, in addition to process considerations such as solvent and reactor selection. PMID- 27680094 TI - Heterogeneous Interaction of Isopropanol with Natural Gobi Dust. AB - The adsorption of isopropanol on Gobi dust was investigated in the temperature (T) and relative humidity (RH) ranges of 273-348 K and <0.01-70%, respectively, using zero air as bath gas. The kinetic measurements were performed using a novel experimental setup combining Fourier-Transform InfraRed spectroscopy (FTIR) and selected-ion flow-tube mass spectrometry (SIFT-MS) for gas-phase monitoring. The initial uptake coefficient, gamma0, of isopropanol was measured as a function of several parameters (concentration, temperature, relative humidity, dust mass). gamma0 was found independent of temperature while it was inversely dependent on relative humidity according to the empirical expression: gamma0 = 5.37 * 10 7/(0.77+RH0.6). Furthermore, the adsorption isotherms of isopropanol were determined and the results were simulated with the Langmuir adsorption model to obtain the partitioning constant, KLin, as a function of temperature and relative humidity according to the expressions: KLin = (1.1 +/- 0.3) * 10-2 exp [(1764 +/- 132)/T] and KLin = 15.75/(3.21+RH1.77). Beside the kinetics, a detailed product study was conducted under UV irradiation conditions (350-420 nm) in a photochemical reactor. Acetone, formaldehyde, acetic acid, acetaldehyde, carbon dioxide, and water were identified as gas-phase products. Besides, the surface products were extracted and analyzed employing HPLC; Hydroxyacetone, formaldehyde, acetaldehyde, acetone, and methylglyoxal were identified as surface products while the formation of several other compounds were observed but were not identified. Moreover, the photoactivation of the surface was verified employing diffuse reflectance infrared fourier transform spectroscopy (DRIFTs). PMID- 27680095 TI - Thermally Assisted Nonvolatile Memory in Monolayer MoS2 Transistors. AB - We demonstrate a novel form of thermally-assisted hysteresis in the transfer curves of monolayer MoS2 FETs, characterized by the appearance of a large gate voltage window and distinct current levels that differ by a factor of ~102. The hysteresis emerges for temperatures in excess of 400 K and, from studies in which the gate-voltage sweep parameters are varied, appears to be related to charge injection into the SiO2 gate dielectric. The thermally-assisted memory is strongly suppressed in equivalent measurements performed on bilayer transistors, suggesting that weak screening in the monolayer system plays a vital role in generating its strongly sensitive response to the charge-injection process. By exploiting the full features of the hysteretic transfer curves, programmable memory operation is demonstrated. The essential principles demonstrated here point the way to a new class of thermally assisted memories based on atomically thin two-dimensional semiconductors. PMID- 27680097 TI - Comment on "Ultrahigh Performance Supercapacitor from Lacey Reduced Graphene Oxide Nanoribbons". PMID- 27680099 TI - Mandibular intraosseous pseudocarcinomatous hyperplasia: a case report. AB - BACKGROUND: Mandibular pseudocarcinomatous hyperplasia is a rare and generally benign pathology. We report on one of these rare cases. CASE PRESENTATION: The case history of a 73-year-old white man stated that he had a carcinoma of the oropharynx, which was primarily treated with radiotherapy and chemotherapy 4 years prior. As a result of radiotherapy he developed an osteoradionecrosis of his mandible and a consecutive pathological fracture of his left mandibular angle. Subsequent osteosynthesis was performed with a reconstruction plate. When we first saw him, his reconstruction plate was partially exposed with intraoral and extraoral fistulation. The resected bone of his defect-bordering jaw showed the typical pathohistological findings of an intraosseous mandibular pseudocarcinomatous hyperplasia. After a first reconstruction attempt with an iliac crest graft failed, definitive reconstruction of his mandible with a microvascular anastomosed fibula graft was achieved. CONCLUSIONS: Intraosseous pseudocarcinomatous hyperplasia of the mandible is a rare differential diagnosis in maxillofacial surgery. Besides other benign epithelial neoplasms, such as calcifying epithelial odontogenic tumor, squamous odontogenic tumor, or different forms of ameloblastoma, the far more frequent invasive squamous cell carcinoma needs to be excluded. A misinterpretation of pseudocarcinomatous hyperplasia as squamous cell carcinoma must be avoided because it can lead to a massive overtreatment. PMID- 27680096 TI - Rh(III)-Catalyzed C-H Functionalization of Indolines with Readily Accessible Amidating Reagent: Synthesis and Anticancer Evaluation. AB - The rhodium(III)-catalyzed direct C-H functionalization of various indolines with 1,4,2-dioxazol-5-ones as new amidating agents is described. This transformation provides efficient preparation of C7-amidated indolines known to display potent anticancer activity. The synthetic compounds were evaluated for in vitro anticancer activity against human prostate adenocarcinoma cells (LNCaP), human endometrial adenocarcinoma cells (Ishikawa), and human ovarian carcinoma cells (SKOV3). Compound 4f was found to be highly cytotoxic, with activity competitive with that of anticancer agent doxorubicin. PMID- 27680098 TI - Is maternal trait anxiety a risk factor for late preterm and early term deliveries? AB - BACKGROUND: Anxiety is associated with preterm deliveries in general (before week 37 of pregnancy), but is that also true for late preterm (weeks 34/0-36/6) and early term deliveries (weeks 37/0-38/6)? We aim to examine this association separately for spontaneous and provider-initiated deliveries. METHODS: Participants were pregnant women from the Norwegian Mother and Child Cohort Study (MoBa), which has been following 95 200 pregnant women since 1999. After excluding pregnancies with serious health complications, 81 244 participants remained. National ultrasound records were used to delineate late preterm, early term, and full-term deliveries, which then were subdivided into spontaneous and provider-initiated deliveries. We measured trait anxiety based on two ratings of the anxiety items on the Symptom Checklist-8 (Acta Psychiatr Scand 87:364-7, 1993). Trait anxiety was transformed into categorizing the score at the mean and at +/- 2 standard deviations. RESULTS: Trait anxiety was substantially associated with late preterm and early term deliveries after adjusting for confounders. In the whole sample, women with the highest anxiety scores (+2 standard deviations) were more likely [(odds ratio (OR) = 1.7; 95 % confidence-interval (CI) 1.3-2.0)] to delivering late preterm than women with the lowest anxiety scores. Their odds of delivering early term were also high (OR = 1.4; CI 1.3-1.6). Women with spontaneous deliveries and the highest anxiety scores had higher odds (OR = 1.4; CI 1.1-1.8) of delivering late preterm and early term (OR = 1.3; CI = 1.3-1.5). The corresponding odds for women with provider-initiated deliveries were OR = 1.7 (CI = 1.2-2.4) for late preterm and OR = 1.3 for early term (CI = 1.01-1.6). Irrespective of delivery onset, women with provider-initiated deliveries had higher levels of anxiety than women delivering spontaneously. However, women with high anxiety were equally likely to have provider-initiated or spontaneous deliveries. CONCLUSIONS: This study is the first to show substantial associations between high levels of trait anxiety and late preterm delivery. Increased attention should be given to the mechanism underlying this association, including factors preceding the pregnancy. In addition, acute treatment should be offered to women displaying high levels of anxiety throughout pregnancy to avoid suffering for the mother and the child. PMID- 27680100 TI - Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk. AB - BACKGROUND: We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose. METHODS: Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n = 2158, age 48.5 +/- 11 years). Over a mean 10.2-years' follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred. RESULTS: Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to "normal-weight", sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose. CONCLUSIONS: Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation. PMID- 27680101 TI - In vivo whole-cell recording with high success rate in anaesthetized and awake mammalian brains. AB - As a critical technique for dissection of synaptic and cellular mechanisms, whole cell patch-clamp recording has become feasible for in vivo preparations including both anaesthetized and awake mammalian brains. However, compared with in vitro whole-cell recording, in vivo whole-cell recording often suffers from low success rates and high access resistance, preventing its wide application in physiological analysis of neural circuits. Here, we describe experimental procedures for achieving in vivo amphotericin B-perforated whole-cell recording as well as conventional (breakthrough) whole-cell recording from rats and mice. The success rate of perforated whole-cell recordings was 70-80 % in the hippocampus and neocortex, and access resistance was 40-70 MOmega. The success rate of conventional whole-cell recordings was ~50 % in the hippocampus, with access resistance of 20-40 MOmega. Recordings were stable, and in awake, head fixed animals, ~50 % whole-cell patched neurons could be held for > 1 hr. The conventional whole-cell recording also permitted infusion of pharmacological agents, such as intracellular blockers of Na+ channels and NMDA receptors. These findings open new possibilities for synaptic and cellular analysis in vivo. PMID- 27680102 TI - The disease of corruption: views on how to fight corruption to advance 21st century global health goals. AB - Corruption has been described as a disease. When corruption infiltrates global health, it can be particularly devastating, threatening hard gained improvements in human and economic development, international security, and population health. Yet, the multifaceted and complex nature of global health corruption makes it extremely difficult to tackle, despite its enormous costs, which have been estimated in the billions of dollars. In this forum article, we asked anti corruption experts to identify key priority areas that urgently need global attention in order to advance the fight against global health corruption. The views shared by this multidisciplinary group of contributors reveal several fundamental challenges and allow us to explore potential solutions to address the unique risks posed by health-related corruption. Collectively, these perspectives also provide a roadmap that can be used in support of global health anti corruption efforts in the post-2015 development agenda. PMID- 27680103 TI - The effects of anaemia and transfusion on patients with traumatic brain injury: A review. AB - BACKGROUND: Anaemia in traumatic brain injury (TBI) is frequently encountered. Neurosurgical texts continue to recommend transfusion for hematocrit below 30%, despite clear evidence to do so. Transfusion should increase oxygen delivery to the brain, but it may also increase morbidity and mortality. METHODS: This study reviewed the relevant literature to better understand the risks of anaemia and benefits of correction of anaemia by transfusion. RESULTS: Of the 21 studies reviewed, eight found that anaemia was harmful to patients with TBI; five found no significant outcome; seven found transfusion was associated with higher rates of morbidity and mortality; two found that transfusion lowered mortality and increased brain tissue oxygen levels; and ten found no correlation between transfusion and outcome. However, the levels of anaemia severity and the outcome measurements varied widely and the majority of outcomes focused on crude measurements rather than detailed functional assessments. CONCLUSIONS: No division of response based on gender difference or impact of anaemia in the post hospital treatment setting was observed. A randomized control trial is recommended to determine the impact of anaemia and transfusion on detailed outcome assessment in comparison of transfusion thresholds ranging from <= 7 g dL 1 to <= 9 g dL-1 in patients with moderate-to-severe TBI. PMID- 27680104 TI - Prognostic biomarker value of binary and grayscale breast tumor histopathology images. AB - AIM: Breast cancer prognosis is in the spotlight owing to its potentially major clinical importance in effective therapeutic management. Following our recent prognostic establishment of the fractal features calculated on binary breast tumor histopathology images, this study aimed to accomplish the first optimization of this methodology by direct comparison of monofractal, multifractal and co-occurrence algorithms in analysis of binary versus grayscale image formats. PATIENTS & METHODS: The study included 93 patients with invasive breast cancer, without systemic treatment and a long median follow-up of 150 months. RESULTS: Grayscale images provided a better prognostic source in comparison to binary, while monofractal, multifractal and co-occurrence image analysis algorithms exerted a comparable performance. CONCLUSION: The critical prognostic importance of the grayscale texture is revealed. PMID- 27680105 TI - Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland. AB - BACKGROUND: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin-norepinephrine reuptake inhibitors. METHODS: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted. RESULTS: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks. CONCLUSION: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland. PMID- 27680106 TI - The relationship between serum YKL-40 levels and arterial stiffness in patients with ankylosing spondylitis. AB - OBJECTIVE: Serum YKL-40 plays roles in inflammatory and vascular processes. Our aim was to evaluate serum YKL-40 levels in patients with ankylosing spondylitis (AS) and to investigate their potential relationship with arterial stiffness based on carotid-femoral pulse wave velocity (CF-PWV). METHODS: Forty-three patients with AS and 41 healthy controls with no history or current signs of cardiovascular disease were included in the study. All patients were administered nonsteroidal anti-inflammatory drugs (NSAIDs), and none were prescribed anti tumor necrosis factor agents. Serum YKL-40 levels were measured. CF-PWV and intima-media thickness of the common carotid artery (IMT-C) were evaluated. RESULTS: The mean age of AS patients was 34.6 +/- 10.2 years and of controls was 36.3 +/- 9.0 years. CF-PWV was significantly higher in AS patients than in controls (8.2+/-2.7 vs.7.0+/-1.6 m/s, respectively; P=0.015). However, the IMT-C was not significantly different between AS patients and controls (0.6+/-0.3 vs. 0.5+/-0.2 mm, P=0.501). YKL-40 levels were significantly higher in AS patients than in controls (78.9+/-37.9 vs. 58.4+/-21.2 ng/mL, P=0.003) and were strongly correlated with CF-PWV (r=0.773, P < 0.001) and IMT-C (r=0.548, P < 0.001). A multiple linear regression analysis revealed that CF-PWV could be explained by serum YKL-40 levels and IMT-C (adjusted R2= 0.707, P=0.013 and P=0.001, respectively). AS patients with a higher disease activity score had higher YKL-40 levels, IMT-C, and CF-PWV than did those with a lower disease activity score (P < 0.001, P=0.008, and P < 0.001, respectively) Conclusion: AS patients had higher serum YKL-40 levels, CF-PWV, and IMT-C than did healthy controls. Additionally, there was an association between increased CF-PWV and serum YKL-40 levels. Therefore, we conclude that CF-PWV and YKL-40 levels may be used for early diagnosis of atherosclerosis in AS patients. PMID- 27680108 TI - Happily ever after? AB - The cheap and cheerful Mills and Boon medical romances are always good for a bit of escapism when you've had a particularly hard day. How accurately these popular paperbacks portray life on a typical hospital ward is questionable, but then they make no claim to documentary status, as Carrie Howse points out in her article on the image of nurses ( page 20 ). PMID- 27680109 TI - Nurses' role in doctors' training is recognised. AB - Nurses' contribution to doctors' training should be formally recognised, a new report has recommended. PMID- 27680110 TI - ? AB - Tower of strength: TV's Birds of a Feather stars Pauline Quirke, left, and Linda Robson are pictured with children from the Queen Elizabeth Hospital for Children in Hackney during a Christmas event organised by the Tower Hill Pageant to raise awareness of the hospital's work. PMID- 27680111 TI - Mixed reaction to savings proposals. AB - There were mixed reactions from nursing unions last week to the Audit Commission report which recommends savings of up to L125 million through better organisation of ward nursing resources. PMID- 27680112 TI - Protest over lack of consultation. AB - The RCN has protested to Health Secretary William Waldegrave over lack of consultation on proposals that GP fundholders will soon be expected to 'buy' district nursing and health visiting services. PMID- 27680113 TI - Sex bias claim after refusal to wear hat. AB - A nurse who was moved from casualty to a theatre recovery ward because she refused to wear a cap has claimed sex discrimination at an industrial tribunal. PMID- 27680107 TI - Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans. AB - Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P < 0.001). Sucrose did not affect the lifespan. Glucose reduced lifespan (P < 0.001). Equal amount of G&F or HFCS reduced lifespan (P < 0.0001). Intestinal fat deposition (IFD) was increased at a higher dose of fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated. PMID- 27680115 TI - Sensible Drinking. AB - Morse code: Inspector Morse star Kevin Gateley helped launch the London regional health authorities' Christmas Sensible Drinking Campaign. He is pictured with Jenny Southam, senior personnel officer for North West Thames Regional Health Authority. The campaign is being run in conjunction with Safeways supermarkets and Alcohol Concern. PMID- 27680116 TI - Stoma care campaign questions impartiality. AB - Concerns about the impartiality of commercially-sponsored stoma nurses were raised at the launch of a new' pressure group, the Campaign tor Impartial Stomacare (CIS). PMID- 27680117 TI - Hotel image will mean fewer staff for Guy's. AB - Guy's Hospital intends to operate like a hotel, with 20 per cent fewer employees, according to the Trust's Chief Executive, Peter Griffiths. PMID- 27680118 TI - Hard line on student tax boosts relief campaign. AB - Student nurses aged under 25 would have to receive a poll tax bill of L595 before they were eligible for Community Charge Benefit, Labour MP lan McCartney was told last week. PMID- 27680119 TI - Living image appeal. AB - A L5-million appeal has been launched by the new Florence Nightingale Fund, a joint venture by Guy's and St Thomas' Hospitals and their United Medical and Dental Schools. PMID- 27680120 TI - ? AB - RCN General Secretary Christine Hancock joined retired members for a special lunch at the College last week in celebration of the RCN's 75th anniversary. PMID- 27680121 TI - Pink accuses RCN of lack of support. AB - Whistleblower Graham Pink has criticised nursing and the Royal College Nursing for 'standing by' when he was sacked for publicising low standards of care. PMID- 27680122 TI - Hancock condemns move to 'casualise' nursing. AB - Fashionable moves to 'casualise' nursing are wholly incompatible with the Audit Commission's findings, Royal College of Nursing General Secretary Christine Hancock said. Qualified hands are simply more 'effective and efficient', she told the conference. PMID- 27680123 TI - ? AB - Scot's missed: a dinner to celebrate John Kelly's retirement as Chair of the RCN Scottish Board was held at the Royal College of Physicians in Edinburgh recently. He is pictured with Isabel Duncan. Secretary to the Board. PMID- 27680126 TI - Welsh plan to aid return to community. AB - The Welsh Office is considering the provision of extra funds to assist in the reintegration into the community of people with learning disabilities, Marion Bull, the Chief Nursing Officer for Wales, told a recent RCN Welsh Board conference. PMID- 27680124 TI - Report heralds start of process of changeAudit commission RCN Conference by Andrey Thompson. AB - The Audit Commission's report on ward nursing resources is just the beginning of the process of change, Commission controller Howard Davies said last week. PMID- 27680127 TI - Parliament. AB - Scotland and Wales are to get their first National Health Service Trusts next April, the Commons was told amid protests against the move. PMID- 27680128 TI - ? AB - Moving message: An exhibition of photographs recording AIDS prevention efforts opened at Abbey Gardens, Westminster to mark World Aids Day. The pictures, by photographer Chris Schwarz, will be on show at the London Lighthouse before being exhibited in other parts of the country . PMID- 27680129 TI - Promoting cultural understanding. AB - Nurses should be in the forefront of promoting cultural understanding and challenging the stereotypes arising from banner headlines such as 'the gay plague' and 'AIDS: the African connection'. PMID- 27680131 TI - Improved recognition of indicators in children. AB - Clinicians are getting very good at predicting which children are actually infected with HIV and which have maternal antibodies, a Royal College of Nursing conference to mark World AIDS Day heard. PMID- 27680130 TI - Redundancies. AB - Nine Staff at the Terrence Higgins Trust are being made redundant because of a L400,000 deficit. A spokesperson said direct services, but obviously when staff the Trust had not been paid by local authorities for the services it provides. PMID- 27680132 TI - Midwives 'pressured to test without consent'. AB - Midwives in some hospitals are under enormous pressure to test patients for HIV before they feel they have informed consent, delegates to the Anglia Polytechnic /Nursing Standard conference on changing attitudes were told. PMID- 27680134 TI - ? AB - Project 2000 students; from Sir Gordon Roberts College of Nursing and Midwifery raised L120 with their World AIDS Day health education display at Nene College. Left to right are: Pete Cobbe, Abie Darkness, Jean Smith and Andrew Birket. PMID- 27680133 TI - Study to focus on lack of courses for GU nurses. AB - Nurses working in genito-urinary medical services are crying out for more training, the Anglia Polytechnic/ Nursing Standard 'AIDS: sharing the challenge - changing attitudes' conference was told. PMID- 27680135 TI - Stress on importance of community nurses. AB - The growing importance of community nurses in caring for people with HIV and AIDS came under the spotlight at Dux- ford. PMID- 27680136 TI - World news. AB - India A British nurse has won an award for her pioneering work with cancer patients in India. PMID- 27680138 TI - Link between epilepsy, convulsions lessened. AB - Children who have febrile convulsions are far less likely to develop epilepsy than was previously thought, a new study shows. PMID- 27680139 TI - Treatment of stroke patients 'deficient'. AB - Many stroke patients receive 'startlingly deficient' treatment, according to a study unveiled at the recent launch of The Stroke Association. PMID- 27680140 TI - Temazepam misused in spite of new formula. AB - Despite a change in the formulation of the drug temazepam, doctors from Charing Cross Hospital have reported that it continues to be injected by intravenous drug abusers. PMID- 27680141 TI - ? AB - Winning smile: A teaching package on 'germ warfare' in intensive care units won Bernadette Grady (right), a nurse at Coventry's Walsgrave Hospital ICU, the Hospital Infection Research Laboratory's Marian Reed Book Prize, sponsored by bedpan manufacturer Vernacare. PMID- 27680142 TI - Elderly regarded as having little worth. AB - Many elderly people continue to be regarded as having little worth or status, in some cases even by the nurses who care for them, an RCN Nurse Agencies Administrators Forum conference was told recently. PMID- 27680143 TI - Early warning signal for heart attacks. AB - A researcher has developed a device which he believes will detect at least half of impending myocardial infarctions. PMID- 27680145 TI - Radial keratotomy for myopia five years on. AB - The outcome of radial keratotomy for myopia is unpredictable for individual eyes, a five-year study suggests. PMID- 27680144 TI - Benefits of hypotensives in the old old. AB - Treating the very elderly for hypertension confers clinically relevant reductions in cardiovascular mortality and morbidity, and total mortality. PMID- 27680146 TI - Dialysis technique for damaged livers. AB - An artificial liver which could act as a short-term support system has been developed by American researchers. PMID- 27680147 TI - Revenge on Montezuma's revenge. AB - Active immunisation with oral cholera vaccine might give partial protection against travellers' diarrhoea, reseachers from Finland say. PMID- 27680148 TI - Sorting the branches. AB - I was horrified to read the news of the English National Board's proposal to merge its Mental Health and Mental Handicap committees. PMID- 27680149 TI - Increase in confidence? AB - As less than 5 per cent of the total membership of the RCN bothered to express an opinion on the rise in the cost of their annual subscription, Council must surely be wondering whether the proposed increase was large enough. PMID- 27680150 TI - Practice nurses need cash backing. AB - The recently published United Kingdom Central Council's proposals for the future of community education and practice will at last enable practice nurses to train for a nationally recordable qualification, on a par with their colleagues in the community. PMID- 27680152 TI - Casualty Update. AB - Casualty is fast becoming a popular vehicle for spreading the feminist message - in a dramatic, rather than placard-waving manner. PMID- 27680151 TI - Fond memories of a matron. AB - I have very different memories of the 'old style' matron than the ones David Wright revealed in his article 'Carry on matron?'(Nursing Standard October 30), and certainly do not think they were all the 'ogres' he describes. PMID- 27680153 TI - Enforcing stereotypes. AB - Although Anne Tennant's article 'Beyond myth and hysteria' ( Nursing Standard November 27) raised the issue of the stereotyping of prostitutes, the picture chosen to accompany it did just that. PMID- 27680154 TI - Just pawns in their game? AB - One of the aspects of nursing which I, a mature student nurse, have found most disturbing over the past two years, is the profession's tendency to be normalistic. PMID- 27680155 TI - Information exchange. AB - The Royal College of Nursing's Unrolled Nurse Fund is seeking applications from enrolled nurses who wish to undertake further study or attend a professional conference or study day. PMID- 27680156 TI - Scare tactics don't work. AB - Breast cancer is the number one cancer killer of women in Britain, killing between 13 and 15,000 women every year. Such facts should be enough to have women seeking out breast screening clinics in droves. Scare tactics alone are not working - especially, it seems, among ethnic minorities. PMID- 27680157 TI - Gossip. AB - It's hat-swap time. This, the last column of 1991, offers a prime slot for a spot of reflection - and an opportunity to swap the old coxcomb for the official Viewpoint Editor's Hat. PMID- 27680158 TI - Tales from the Turf Bernard J and H Dodd Weidenfeld & Nicolson 64pp L9.99 0-297 81 164-9 [Formula: see text]. AB - Jeffrey Bernard claims that he lives an unremarkable life - and earns a living writing about it as a regular columnist for The Spectator. PMID- 27680159 TI - The Faber Book of Madness R Porter The Faber Book of Madness , editor Faber 572pp L14.99 0-571-14387-3 [Formula: see text]. AB - Dipping into an anthology of 'madness' is a bit like running round a blind corner with a bag over your head; you never quite know what you're going to run into. PMID- 27680161 TI - The challenge of the nineties. AB - What images come to mind when you think of The Netherlands? For most of us windmills, canals and tulips will be fairly close to the top of the list. Perhaps somewhat lower in the pecking order is the national reputation for relaxed attitudes to drugs and sex. PMID- 27680163 TI - Listings. PMID- 27680162 TI - Images of Romania. AB - Thousands of nurses contributed to this book: all those who gave time and money to the Nursing Standard Caring for Romania Appeal and the Romanian Angel Appeal. PMID- 27680164 TI - DIAGNOSTIC PERFORMANCE EVALUATION OF THE SD BIOLINE MALARIA ANTIGEN AG PF/PAN TEST (05FK60) IN A MALARIA ENDEMIC AREA OF SOUTHERN ETHIOPIA. AB - Rapid diagnostic tests (RDTs) capable of detecting and differentiating Plasmodium species are needed in areas in which microscopy is unsuitable. This study was conducted to assess the diagnostic performance of the rapid test kit - SD BIOLINE Malaria Ag Pf/Pan(r) (05FK60) in an endemic area. Microscopy of Giemsa-stained blood films were performed to detect and estimate the Plasmodium density in malaria suspected patients. The performance of the SD BIOLINE Malaria Ag Pf/Pan test was evaluated using 272 Plasmodium-positive and 102 negative blood samples. The overall sensitivity of the SD BIOLINE Malaria Ag Pf/Pan test was 99.5% for P. falciparum and 92.6% for non-P. falciparum malaria infections. The respective specificity, PPV, and NPV of the test were 98.0, 98.4, and 99.0% for the diagnosis of P. falciparum, and 100.0 %, 100.0%, and 94.4% for non-P. falciparum species. The SD BIOLINE Malaria Ag Pf/Pan test showed an excellent performance in diagnosing Plasmodium infections in an endemic setting. Therefore, this point-of care test could be used as an alternative to microscopy in places where P. falciparum is endemic and microscopy is unsuitable. PMID- 27680165 TI - COMPARISON OF METHODS TO IDENTIFY Neisseria meningitidis IN ASYMPTOMATIC CARRIERS. AB - Neisseria meningitidis is a cause of several life-threatening diseases and can be a normal commensal in the upper respiratory tract of healthy carriers. The carrier rate is not well established especially because there is no standard method for the isolation of N. meningitidis. Therefore, the aim of this study was to compare identification methods for the carrier state. Two swabs were collected from 190 volunteers: one was cultured and the other had DNA extracted directly from the sample. The Polymerase Chain Reaction (PCR) was performed to determine species and serogroups and compared the results between the methods. PCR for species determination used two pairs of primers and when there was only one amplicon, it was sequenced. The culture technique was positive in 23 (12.1%) subjects while the direct extraction method was positive in 132 (69.5%), p < 0.001. Among the 135 subjects with positive N. meningitides tests, 88 (65.2%) were serogroup C; 3 (2.2%) serogroup B; 5 (3.7%) were positive for both serogroup B and C, and 39 (28.9%) did not belong to any of the tested serogroups. In this study, PCR from DNA extracted directly from swabs identified more N. meningitidis asymptomatic carriers than the culture technique. PMID- 27680166 TI - Trichomonas vaginalis PREVALENCE AND RISK FACTORS FOR WOMEN IN SOUTHERN BRAZIL. AB - Trichomonas vaginalis infections have been associated with other diseases so that epidemiological studies of the parasite are important and help to prevent the spread of the disease. This study aimed to determine the prevalence of T. vaginalis in female patients of 19 counties in southwestern Rio Grande do Sul, Brazil. For diagnosis, was used direct examination, followed by applying a socio epidemiological questionnaire. We analyzed 300 women and 9% were infected by Trichomonas vaginalis. The highest frequency occurred in women between 18 and 39 years old, single/divorced/widowed, whose family income was at one minimum wage or less, and they had not completed the primary school. Statistically significant risk factors were: women reporting two or more sexual partners in the last year were 3.3 times more likely to acquire the parasite, and those in use of oral contraceptives were 2.7 times more likely to have T. vaginalis. Importantly, 33% of the asymptomatic women were infected, and most of the negative results were from women presenting symptoms consistent with the infection. The findings emphasize that it is necessary to expand the knowledge of individuals about the disease, especially among women with the above mentioned risk factors and also to include the regular screening of Trichomonas vaginalis infections in health centers. PMID- 27680167 TI - FREQUENCY OF ANTI- Toxocara spp. ANTIBODIES IN INDIVIDUALS ATTENDED BY THE CENTRO DE SALUD FAMILIAR AND ENVIRONMENTAL CONTAMINATION WITH Toxocara canis EGGS IN DOG FECES, IN THE COASTAL NIEBLA TOWN, CHILE. AB - The frequency of anti-Toxocara spp. antibodies in individuals attended by the Centro de Salud Familiar in the coastal Niebla town, Chile, was related to the host and to environmental factors. IgG anti- Toxocara antibodies were detected with a commercial ELISA kit (SCIMEDX Corporation, USA). Samples with undetermined absorbance values were subjected to an additional ELISA standardized by the Instituto de Salud Publica, Chilean Health Ministry, a commercial ELISA (NOVATEC, Germany), and a commercial Western blot kit (LDBio Diagnostics, France). Hematological exams were performed using an automated blood counter and blood smears. Dog feces were collected from the ground along the main road in Niebla, including rural and urban locations. Ninety (25.4%) of the 355 examined individuals were positive by the ELISA test. The frequency of anti-Toxocara antibodies and the infection risk were significantly higher (p < 0.05) among those individuals >= 40 years old with respect to the 20-39 years old group, in individuals from rural locations, those who did not have a safe drinking water supply in the house or who presented blood eosinophilia. The proportion of positive samples of dog feces and the mean number of Toxocara canis eggs/g of feces in urban and rural areas were similar (p > 0.05). PMID- 27680168 TI - DIAGNOSIS OF Strongyloides stercoralis INFECTION IN IMMUNOCOMPROMISED PATIENTS BY SEROLOGICAL AND MOLECULAR METHODS. AB - Strongyloidiasis is a potentially serious infection in immunocompromised patients. Thus, the availability of sensitive and specific diagnostic methods is desirable, especially in the context of immunosuppressed patients in whom the diagnosis and treatment of strongyloidiasis is of utmost importance. In this study, serological and molecular tools were used to diagnose Strongyloides stercoralis infections in immunosuppressed patients. Serum and stool samples were obtained from 52 patients. Stool samples were first analyzed by Lutz, Rugai, and Agar plate culture methods, and then by a quantitative real time polymerase chain reaction (qPCR). Serum samples were evaluated by an enzyme-linked immunosorbent assay (ELISA) using a soluble (AS) or a membrane fractions antigen (AM) obtained from alkaline solutions of the filariform larvae of Strongyloides venezuelensis. Of the 52 immunosuppressed patients, three (5.8%) were positive for S. stercoralis by parasitological methods, compared to two patients (3.8%) and one patient (1.9%) who were detected by ELISA using the AS and the AM antigens, respectively. S. stercoralis DNA was amplified in seven (13.5%) stool samples by qPCR. These results suggest the utility of qPCR as an alternative diagnostic tool for the diagnosis of S. stercoralis infection in immunocompromised patients, considering the possible severity of this helminthiasis in this group of patients. PMID- 27680169 TI - COMPARISON OF 16S rRNA-PCR-RFLP, LipL32-PCR AND OmpL1-PCR METHODS IN THE DIAGNOSIS OF LEPTOSPIROSIS. AB - Leptospirosis is still one of the most important health problems in developing countries located in humid tropical and subtropical regions. Human infections are generally caused by exposure to water, soil or food contaminated with the urine of infected wild and domestic animals such as rodents and dogs. The clinical course of leptospirosis is variable and may be difficult to distinguish from many other infectious diseases. The dark-field microscopy (DFM), serology and nucleic acid amplification techniques are used to diagnose leptospirosis, however, a distinctive standard reference method is still lacking. Therefore, in this study, we aimed to determine the presence of Leptospira spp., to differentiate the pathogenic L. interrogans and the non-pathogenic L. biflexa, and also to determine the sensitivity and specificity values of molecular methods as an alternative to conventional ones. A total of 133 serum samples, from 47 humans and 86 cattle were evaluated by two conventional tests: the Microagglutination Test (MAT) and the DFM, as well as three molecular methods, the 16S rRNA-PCR followed by Restriction Fragment Lenght Polymorphism (RFLP) of the amplification products 16S rRNA-PCR-RFLP, LipL32-PCR and OmpL1-PCR. In this study, for L. interrogans, the specificity and sensitivity rates of the 16S rRNA-PCR and the LipL32-PCR were considered similar (100% versus 98.25% and 100% versus 98.68%, respectively). The OmpL1-PCR was able to classify L. interrogans into two intergroups, but this PCR was less sensitive (87.01%) than the other two PCR methods. The 16S rRNA-PCR-RFLP could detect L. biflexa DNA, but LipL32-PCR and OmpL1-PCR could not. The 16S rRNA-PCR-RFLP provided an early and accurate diagnosis and was able to distinguish pathogenic and non-pathogenic Leptospira species, hence it may be used as an alternative method to the conventional gold standard techniques for the rapid disgnosis of leptospirosis. PMID- 27680170 TI - ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL. AB - Introduction:: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(-) chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods:: Patients presenting HBsAg(+) for more than six months, Anti-HBe(+)/HBeAg(-), viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F >= 2 and/or A >= 2 by the METAVIR classification. Results:: 11/27 (40.7%) patients had advanced liver injury, with a mean viral load of 701.0 (+/- 653.7) IU/mL versus 482.8 (+/- 580.0) IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37). The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions:: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment. PMID- 27680171 TI - POTENTIAL CROSS-CONTAMINATION OF SIMILAR Giardia duodenalis ASSEMBLAGE IN CHILDREN AND PET DOGS IN SOUTHERN BRAZIL, AS DETERMINED BY PCR-RFLP. AB - Giardia duodenalis is an enteric parasite that has distinct genetic groups. Human infections are mainly caused by assemblages A and B, although sporadic infections by assemblages C and D have also been reported. Animals can be infected by a wide range of assemblages (A to H). The aim of this study is to identify the assemblages and sub-assemblages of G. duodenalis with zoonotic features in fecal samples of school-aged children, and in dogs that coexist in the same households in Lages, Santa Catarina, Brazil. Fecal samples of 91 children and 108 dogs were obtained and G. duodenalis cysts were detected in samples from 11 (12.08%) children and 10 (9.25%) dogs. DNA extracted from the 21 positive samples was analyzed by PCR-RFLP, using the gdh gene. Results showed the presence of sub assemblages AI (2/11), AII (4/11), BIII (2/11), and BIV(3/11) among children and AI (5/10) and BIV(3/10) in dogs, with zoonotic characteristics, and the carnivore specific assemblage C (2/10). G. duodenalis was found to infect both children and dogs living in the same household, with the same sub-assemblage (BIV) indicating that pet dogs are a potential risk of transmission of G. duodenalis to humans. PMID- 27680172 TI - EVOLUTION OF AMERICAN TEGUMENTARY LEISHMANIASIS CASES REPORTED IN PARANA STATE, BRAZIL. AB - Leishmaniases are infectious diseases caused by protozoa of the genus Leishmania. They are widely distributed worldwide and endemic in 88 countries in four continents. The present study analyzed the reported cases of American Tegumentary Leishmaniasis (ATL) in Parana State (Brazil) from January 2007 to December 2013. The data were grouped according to Regional Health (RH) districts and macroregions, which allowed visualization of the reality in each region in the state. A total of 2,879 ATL cases were reported and distributed among the 22 RH districts, with an average detection rate of 3.9 cases per 100,000 inhabitants. The northwestern region accounted for 50.1% of the total cases, and the northern region accounted for 26.0-76.1% of the reported cases. The 6th RH district did not report any cases. The 7th, 9th, and 18th RH districts had a higher cure rate (> 80%), and lower cure rates were found in the 1st, 4th, and 12th RH districts. Reported unfavorable outcomes included treatment abandonment and death. Overall cure rates are based on the entire country, and unfavorable outcomes require greater attention of managers and health professionals to meet the goals of the Brazilian Ministry of Health. PMID- 27680173 TI - PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS. AB - American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL. PMID- 27680175 TI - SEROPREVALENCE AND RISK FACTORS ASSOCIATED WITH Toxoplasma gondii INFECTION AMONG RURAL COMMUNITIES IN NORTHERN IRAN. AB - Toxoplasmosis is the fourth most common cause of hospitalization and the second cause of death due to food-borne infections. We conducted a cross-sectional study to determine the prevalence, disease awareness and risk factors associated with toxoplasmosis among rural communities in Northern Iran. Data were obtained from serological testing and from participant's questionnaires and were analyzed using a logistic regression. Of the 630 participants, 465 (73.8%), and 12 (1.9%) had IgG and both IgG and IgM anti-Toxoplasma gondii antibodies, respectively. In the logistic regression analysis, T. gondii seropositivity was associated with the following factors: age, occupation, consumption of undercooked meat, and of unwashed raw vegetables or fruits (p < 0.001). Our study showed a high prevalence of T. gondii infection in the general population of Northern Iran. A health program is needed to increase the public awareness of toxoplasmosis, and its associated risk factors. PMID- 27680174 TI - ANTIFUNGAL SUSCEPTIBILITY TESTING AND GENOTYPING CHARACTERIZATION OF Cryptococcus neoformans AND gattii ISOLATES FROM HIV-INFECTED PATIENTS OF RIBEIRAO PRETO, SAO PAULO, BRAZIL. AB - Cryptococcosis is a leading invasive fungal infection in immunocompromised patients. Considering the high prevalence and severity of these infections in immunocompromised patients attended at HC-FMRP-USP, the present research aimed to characterize the clinical isolates of Cryptococcus strains by biochemical and molecular methods and evaluate antifungal susceptibility of clinical isolates. Fifty isolates from 32 HIV-positive patients were obtained at HC-FMRP-USP. Most of the isolates (78.1%) were identified as C. neoformans, and 100% of C. neoformans and C. gattii strains were susceptible to amphotericin B, ketoconazole and fluconazole. All isolates were classified as serotype A (grubbii variety) by PCR and most of them were characterized in mating type MATa. PCR analysis of specific M13 microsatellite sequence revealed that VNI type was predominant among C. neoformans, while VGII was predominant among C. gattii. The strains did not show a significant resistance to the antifungals tested, and Canavanine-Glycine Bromthymol Blue Agar (CGB) proved to be a reliable test presenting a good correlation with the molecular characterization. C. neoformans isolated from disseminated infections in the same patient showed molecular identity when different anatomical sites were compared; besides, the studied strains did not present a significant increase in resistance to antifungal agents. In addition, the homogeneity of the molecular types and detection of the mating types suggested a low possibility of crossing among the strains. PMID- 27680176 TI - STATUS OF THE AMERICAN TEGUMENTARY LEISHMANIASIS IN THE STATE OF RIO DE JANEIRO , BRAZIL, FROM 2004 TO 2013. AB - The aim of the present study was to analyze the status of the American Tegumentary Leishmaniasis (ATL) in the state of Rio de Janeiro, from 2004 to 2013, through its spatiotemporal distribution. We also described variables considered relevant to the epidemiology of the disease, such as the clinical form, gender, ethnic group, age group, and progression of disease. This is a descriptive study, which used notified secondary data from the Brazilian Information System of Notifiable Diseases (SINAN), Ministry of Health, Brazil, regarding confirmed diagnoses. To help the calculation of coefficients of detection and mortality, we used population data from the Brazilian Institute of Geography and Statistics (IBGE). We analyzed 1,470 cases of ATL with the predominance of the cutaneous clinical form (1,292/87.89%). The data has also revealed seven deaths, a predominance of males (922/62.72%), and a higher incidence of ATL in the white ethnic group (731/49.72%). We observed a high incidence of ATL in the group of 20 - 39 years old (477/32.44%). We concluded that there was a decrease in the number of ATL cases in the state of Rio de Janeiro, based on a coefficient of detection of 1.44/100.000 inhabitants in 2004 decreasing to 0.20/100.000 inhabitants in 2013. The localities with the highest occurrences of ATL were the metropolitan region (843 cases) and the municipality of Rio de Janeiro (740 cases). In 2005, the highest incidence of the disease was observed (351 cases) in the study. Among the variables selected to describe the epidemiology of the disease, the following categories: cutaneous clinical form, male patients, white ethnic group, and the age group of 20 - 39 years old were more affected than the others. PMID- 27680177 TI - EVALUATION OF CIRCUMSPOROZOITE PROTEIN OF Plasmodium vivax TO ESTIMATE ITS PREVALENCE IN OIAPOQUE , AMAPA STATE, BRAZIL, BORDERING FRENCH GUIANA. AB - Malaria is a major health problem for people who live on the border between Brazil and French Guiana. Here we discuss Plasmodium vivax distribution pattern in the town of Oiapoque, Amapa State using the circumsporozoite (CS) gene as a marker. Ninety-one peripheral blood samples from P. vivax patients have been studied. Of these, 64 individuals were from the municipality of Oiapoque (Amapa State, Brazil) and 27 patients from French Guiana (August to December 2011). DNA extraction was performed, and a fragment of the P. vivax CS gene was subsequently analyzed using PCR/RFLP. The VK210 genotype was the most common in both countries (48.36% in Brazil and 14.28% in French Guiana), followed by the P. vivax-like (1.10% in both Brazil and French Guiana) and VK247 (1.10% only in Brazil) in single infections. We were able to detect all three CS genotypes simultaneously in mixed infections. There were no statistically significant differences either regarding infection site or parasitaemia among individuals with different genotypes. These results suggest that the same genotypes circulating in French Guiana are found in the municipality of Oiapoque in Brazil. These findings suggest that there may be a dispersion of parasitic populations occurring between the two countries. Most likely, this distribution is associated with prolonged and/or more complex transmission patterns of these genotypes in Brazil, bordering French Guiana. PMID- 27680180 TI - The Proceedings of the 217th Kanto-Koshinetsu Regional Meeting of the Japanese Society of Neurology. PMID- 27680179 TI - The Proceedings of the 2016 Chugoku-Shikoku Regional Post Graduate Education Meeting. PMID- 27680182 TI - Editor's Note. PMID- 27680178 TI - SILVER NANOPARTICLES-DISK DIFFUSION TEST AGAINST Escherichia coli ISOLATES. AB - Nanotechnology can be a valuable ally in the treatment of infections. Silver nanoparticles (AgNPs) are structures that have antimicrobial activity. The aim of this study was to produce AgNPs by green methods, characterize these structures, and assess their antimicrobial activity against Escherichia coli associated with the antibiotic ciprofloxacin. AgNPs were characterized by spectroscopic and microscopic techniques. Antimicrobial activity was evaluated by the disk diffusion method against 10 strains of E. coli. The synthesized AgNPs showed a spherical shape and a size of 85.07 +/- 12.86 nm (mean +/- SD). AgNPs increased the activity of ciprofloxacin by 40% and may represent a new therapeutic option for the treatment of bacterial infections. PMID- 27680184 TI - Cellular and humoral inflammatory response after laparoscopic and conventional colorectal surgery. Preliminary report. AB - : Our aim is to compare the immune response after colorectal surgery performed laparoscopically and via traditional technique. This response seems to be proportional to the level of the surgical trauma and presumably is directed to improve host defence. This is a prospective reported study based on patients' randomisation. Fourteen patients with colorectal diseases undergoing laparoscopic or open surgery were enrolled. After both laparoscopic and open colorectal surgery, we observed a significant increase of circulating C-Reactive Protein (CRP) levels. The count of lymphocytes subpopulations did not show significant differences after both procedures. IL-6 serum levels increased immediately after laparoscopic approach. IL-6 production was preserved only in the laparoscopic group, while its plasma levels were significantly higher in conventional group. Postoperative cell-mediated immunity was better preserved after laparoscopic than after conventional colorectal resection. Laparoscopy became a popular approach to treat surgically benign and malignant colorectal diseases and several authors reported a better immune response in patients performing laparoscopic surgery after comparing to conventional colorectal surgery. These findings may have important implications in performing a laparoscopic colorectal resection. KEY WORDS: C-Reactive Protein IL-6, Laparoscopic Surgery. PMID- 27680185 TI - Improving outcomes in the management of Gram-negative bacterial infections in the face of growing antimicrobial resistance. AB - 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2016): 9-12 April 2016, Amsterdam, The Netherlands The European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), the annual meeting of the European Society of Clinical Microbiology, had a record attendance at the 2016 meeting, with more than 11,600 scientists and clinicians from 120 countries sharing the latest research and information on infectious diseases. This article reviews sessions on the growing threat of antibiotic resistance in the management of Gram-negative bacterial infections and potential solutions, including optimizing initial drug choice and dosing, development of new options and improving antimicrobial stewardship. PMID- 27680183 TI - An efficient route to bispecific antibody production using single-reactor mammalian co-culture. AB - Bispecific antibodies have shown promise in the clinic as medicines with novel mechanisms of action. Lack of efficient production of bispecific IgGs, however, has limited their rapid advancement. Here, we describe a single-reactor process using mammalian cell co-culture production to efficiently produce a bispecific IgG with 4 distinct polypeptide chains without the need for parallel processing of each half-antibody or additional framework mutations. This method resembles a conventional process, and the quality and yield of the monoclonal antibodies are equal to those produced using parallel processing methods. We demonstrate the application of the approach to diverse bispecific antibodies, and its suitability for production of a tissue specific molecule targeting fibroblast growth factor receptor 1 and klotho beta that is being developed for type 2 diabetes and other obesity-linked disorders. PMID- 27680186 TI - Introduction: Factors Underlying Social Functioning in Schizophrenia: Information Processing and Social Perception. PMID- 27680188 TI - [Immunooncology in Urologic Cancers: Current Status]. AB - Immune checkpoint inhibitors are establishing itselves as a new systemic treatment option (in addition to chemotherapy and targeted therapy) for metastatic tumours. (Re)activating the immune system, these antibodies may lead to impressive remissions lasting for a long time in some patients. Regarding urological tumours, the anti-PD-1 antibody Nivolumab (Opdivo((r))) has been approved this year for advanced, previously treated renal cell carcinoma. In the United States, Atezolizumab (Tecentriq((r))) has been approved for metastatic urothelial carcinoma after platinum-based chemotherapy. In patients pre-treated with antiangiogenic drugs, Nivolumab has achieved a higher rate of remission (25 vs. 5%) and a 5.4-month increase in overall survival compared with Everolimus. An indirect comparison with chemotherapy demonstrates an increased remission rate (15%) and an increased 1-year survival rate (37%) for urothelial carcinoma after platinum-based chemotherapy with Atezolizumab. The frequency of side-effects resulting from these treatments is comparatively low. However, some patients experience what is called immune-mediated side-effects, which must be recognised and treated in a timely manner. Immune checkpoint inhibitors are being tested in numerous ongoing phase III clinical trials and have the potential to replace current first-line treatment options for metastatic tumours such as urothelial and renal cell carcinoma. These trials are also investigating anti-PD-1/anti-PD L1 antibodies in combination with CTLA4 immune checkpoint inhibitors or antiangiogenic treatments. Approval trials are also investigating the role of immune checkpoint inhibitors in the adjuvant setting. PMID- 27680190 TI - [Primary Tumour Treatment in Patients with Metastatic Prostate Cancer]. AB - Prostate cancer (PCa) with distant metastasis at diagnosis (M1) is associated with an unfavourable prognosis. Therefore, according to current treatment guidelines, local treatment (radical prostatectomy or irradiation of the prostate gland) is not recommended in men with M1 disease. However, M1 patients inevitably develop castration-resistant disease progression leading to local complications in half of men. Hence, local treatment, if reconcilable with a good quality of life, would have the potential to prevent future local symptoms. Furthermore, evolving data from genomic studies suggest that local treatment might have the potential to reduce further spread of lethal cancer clones by eliminating the primary tumour or nodal metastasis. This leads to the experimental concept of cytoreductive preventative local treatment. According to large US-American and German cancer registries, there is a growing body of evidence pointing towards a survival benefit for M1 patients who receive local treatment in combination with systemic therapy. These data provide the basis to generate the hypothesis of a better response to systemic tumour therapy in metastatic prostate cancer, which would be the rationale for prospective randomised trials, but would not suffice for a treatment recommendation to be given. While there is a dynamic paradigm shift in the systemic treatment of hormone-naive M1 prostate cancer, local treatment for primary tumours will only have a chance to be established in this indication if prospective randomised trials are successfully completed. PMID- 27680189 TI - [Implications of PI-RADS Version 1 and Updated Version 2 on the Scoring of Prostatic Lesions in Multiparametric MRI]. AB - BACKGROUND: A revised version of the PI-RADS scoring system has been introduced and score-related variability between version 1 and 2 may be suspected. This study aimed to assess the PI-RADS scores derived from version 1 (v1) and the updated version 2 (v2). MATERIAL AND METHODS: 61 patients with biopsy-proven prostate cancer (PCa) and 90 lesions detected on pre-biopsy 3-Tesla multiparametric MRI were included in this retrospective analysis. 2 experienced radiologists scored all lesions in consensus. Lesion scores differing between PI RADS v1 and v2 were further analyzed. Histology data from radical prostatectomy (RP) were included when available. RESULTS: The PI-RADS v1 and v2 score differed in 52% of patients (32/61) and in 39% of lesions (35/90). On a lesion basis, the reason for the differences were related to sum score in v1 vs. categorical system in v2 in 51% (18/35) of lesions, cutoff between PI-RADS 4 and 5 based on lesion size in v2 as opposed to the sum score in v1 in 31% (11/35) and were inconclusive in 17% (6/35). The RP subgroup indicates enhanced detection of PCas with GS 3+3 and GS 3+4 in v2. CONCLUSION: PI-RADS scores of prostatic lesions frequently differed between v1 and v2, the major reasons for these differences being score related. In men undergoing RP, PI-RADS v2 improved detection of low risk PCa, but did not increase accuracy for discrimination of GS 3+4 vs. GS>=4+3 compared to v1. Urologists should be aware of the system-related differences when interpreting PI-RADS scores. PMID- 27680191 TI - [Strategies for First-Line Treatment of mCRPC]. AB - At present, abiraterone acetate and enzalutamide are the most commonly used substances in the first-line treatment of asymptomatic or mildly symptomatic metastatic castration-resistant prostate carcinoma (mCRPC). Since the relevant pivotal trials have demonstrated comparable clinical efficacy for both substances, further factors should be considered for the choice of treatment. As mCRPC patients usually receive several lines of treatment, different adaptation and resistance mechanisms leading to treatment failure could be important. This is indicated by daily routine observations and some initial clinical studies on resistance and different sequences of therapy. However, until the clinical relevance has been confirmed, it is mostly adverse events and comorbidities that are taken into account for the choice of first-line therapy. Also potential interactions with comedications and patient preferences should be considered. In the first-line treatment of mCRPC, ongoing discussions not only centre around the choice of medication for first-line mCRPC therapy, but also around the point in time they are started. For abiraterone acetate, for example, there is confirmed evidence that patients may benefit from early use within the approved indication. If the clinical importance of the different resistance mechanisms and differences in efficacy of various sequences could be confirmed, this would be a strong argument for therapy decisions and should therefore be further analysed in prospective clinical studies. PMID- 27680192 TI - [Significance and Importance of Pelvic Lymphadenectomy in Low-Risk Prostate Cancer Patients]. AB - BACKGROUND: The most frequent carcinoma in male patients is prostate cancer. D'Amico and colleagues (1998) set up a classification to assess the aggressiveness of prostate cancer growth and the risk of metastatic spread, taking into account the following parameters: PSA, Gleason Score (GS), and tumour spread (T). The combination of these parameters results in a classification of low-, intermediate- and high-risk patients.In the context of a larger heuristic study entitled "Low-Risk Prostate Cancer Patients: Significance And Importance Of Pelvic Lymphadenectomy in Localized Prostate Carcinomas", we observed the correlation of the parameters PSA, GS and T stage with the occurrence of lymph node metastases in low-risk-patients who underwent lymphadenectomy during radical prostatectomy. PATIENTS/MATERIALS AND METHODS: Due to a lack of evidence - none of the confirmed LR (low-risk=LR) patients was diagnosed with metastases - we set up a subclassification for LR patients for the following corridor transition zone between low-risk and high-risk patients (based on the D'Amico classification):PSA<=10 ng/ml and GS<=7a (c: 7a) and clinical stage T1a-T2c (c: T2b, T2c): The population consists of 288 prostate cancer patients (60 low-risk (LR) patients, 228 corridor (c) patients). We analysed the number and frequency of removed lymph nodes and lymph node metastases. Moreover, we analysed the population with a view to a postoperative GS upgrade. The results are based on heuristic methods. RESULTS: The situation regarding the data in the transition zone, i. e. in the corridor area, and in the verified low-risk range is very complicated:In total, 3 743 lymph nodes were removed in 288 patients (mean: 13 lymph nodes). Of these only 7 lymph nodes in 5 patients from the corridor group were metastatic. The overall number of removed lymph nodes in these 5 patients lies within a small interval [23,32]; 26 lymph nodes were removed on average. A postoperative Gleason Score upgrade was found in 20.14% of the whole patient population. CONCLUSION: A postoperative Gleason Score upgrade in every fifth patient shows a highly relevant preoperative undergrading in these patients, which may lead to inadequate treatment. An opening of the D'Amico classification to include a corridor category of patients could be an opportunity to minimise preoperative undergrading. In this context, pelvic lymphadenectomy must be considered, at least for corridor patients. PMID- 27680193 TI - [Not Available]. PMID- 27680194 TI - Ex vivo characterization of a novel tissue-like cross-linked fibrin-agarose hydrogel for tissue engineering applications. AB - The generation of biomaterials with adequate biomechanical and structural properties remains a challenge in tissue engineering and regenerative medicine. Earlier research has shown that nanostructuration and cross-linking techniques improved the biomechanical and structural properties of different biomaterials. Currently, uncompressed and nanostructured fibrin-agarose hydrogels (FAH and NFAH, respectively) have been used successfully in tissue engineering. The aim of this study was to investigate the possibility of improving the structural and biomechanical properties of FAH and NFAH by using 0.25% and 0.5% (v/v) glutaraldehyde (GA) as a cross-linker. These non-cross-linked and cross-linked hydrogels were subjected to structural, rheological and ex vivo biocompatibility analyses. Our results showed that GA cross-linking induced structural changes and significantly improved the rheological properties of FAH and NFAH. In addition, ex vivo biocompatibility analyses demonstrated viable cells in all conditions, although viability was more compromised when 0.5% GA was used. Our study demonstrates that it is possible to control fiber density and hydrogel porosity of FAH and NFAH by using nanostructuration or GA cross-linking techniques. In conclusion, hydrogels cross-linked with 0.25% GA showed promising structural, biochemical and biological properties for use in tissue engineering. PMID- 27680197 TI - Asymmetric Synthesis of Isoquinoline Alkaloids: 2004-2015. AB - In the past decade, the asymmetric synthesis of chiral nonracemic isoquinoline alkaloids, a family of natural products showing a wide range of structural diversity and biological and pharmaceutical activity, has been based either on continuation or improvement of known traditional methods or on new, recently developed, strategies. Both diastereoselective and enantioselective catalytic methods have been applied. This review describes the stereochemically modified traditional syntheses (the Pictet-Spengler, the Bischler-Napieralski, and the Pomeranz-Fritsch-Bobbitt) along with strategies based on closing of the nitrogen containing ring B of the isoquinoline core by the formation of bonds between C1 N2, N2-C3, C1-N2/N2-C3, and C1-N2/C4-C4a atoms. Methods involving introduction of substituents at the C1 carbon of isoquinoline core along with syntheses applying various biocatalytic techniques have also been reviewed. PMID- 27680195 TI - Perceptions of Harm and Reasons for Misuse of Prescription Opioid Drugs and Reasons for Not Seeking Treatment for Physical or Emotional Pain Among a Sample of College Students. AB - BACKGROUND: Since the early 1990s, the United States has seen a significant increase in the prevalence of prescription opioid misuse. Despite benefits prescription opioids provide, misuse can be fatal. OBJECTIVES: The current study was designed to investigate the prevalence of prescription opioid misuse, perceived harm of misuse, and reasons for misuse for physical or emotional pain instead of seeking professional medical or mental health treatment. METHODS: Survey data were collected in the fall of 2013 via an online survey to a random sample of 668 students from a public Midwestern university. RESULTS: Lifetime prevalence of prescription opioid misuse was 9.5%. Misusers of prescription opioid drugs generally reported lower ratings of perceived harm as compared to individuals not reporting misuse of prescription opioid drugs. Primary reasons for misuse of prescription opioid drugs was to relieve pain (33.9%), "to feel good/get high" (23.2%) and experimentation (21.4%). Lifetime misuse of a prescription opioid drug for physical or emotional pain was reported by 8.1% and 2.2% of respondents, respectively. Primary reasons for misuse for physical pain included because pain was temporary, immediate relief was needed, and no health insurance/financial resources. Primary reasons for misuse for emotional pain included not wanting others to find out, embarrassment and fear. Conclusions/Importance: Reasons for misuse of prescription opioid drugs vary by type of prescription opioid drug. Reasons for not seeking treatment that ultimately lead to misuse, vary by type of pain being treated and may be important considerations in the effort to stem the misuse of prescription opioid drugs among college students. PMID- 27680196 TI - Can MDCT Unmask Instability in Binder-Stabilized Pelvic Ring Disruptions? AB - OBJECTIVE: Pelvic binders may hinder radiologic assessment of pelvic instability after trauma, and avulsive injuries can potentially unmask instability in this setting. We compare the performance of MDCT for the detection of pelvic disruptions in patients with binders to a matched cohort without binders, and we assess the utility of avulsive injuries as signs of pelvic instability. MATERIALS AND METHODS: MDCT examinations of 56 patients with binders were compared with MDCT examinations of 54 patients without binders. Tile grading by an experienced orthopedic surgeon was used as the reference standard (A, stable; B, rotationally unstable; C, rotationally and vertically unstable). Two radiologists performed blinded reviews of CT studies in two reading sessions (sessions 1 and 2). In session 1, Tile grade was predicted on the basis of established signs of instability, including pubic symphysis and sacroiliac (SI) joint widening. In session 2, readers could change the Tile grade when avulsive injuries were seen. Diagnostic performance for predicting rotational instability and vertical instability was assessed. RESULTS: In the binder group, AUCs under the ROC curves for rotational instability increased from fair (0.73-0.77) to good (0.82-0.89) when avulsive signs were considered. In the control group, AUCs were good in both sessions. AUCs for vertical instability were fair with binders in both sessions. Agreement with the reference standard increased from fair (0.30-0.32) to moderate (0.46-0.54) when avulsive signs were considered in the binder group but were in the moderate range for both sessions in the control group. Combined evaluation for inferolateral sacral fractures, ischial spine fractures, and rectus abdominis avulsions resulted in optimal discrimination of rotational instability. CONCLUSION: Evaluation for avulsive signs improves MDCT sensitivity for the detection of rotational instability but not vertical instability in patients with binders. PMID- 27680198 TI - Bartolosides E-K from a Marine Coccoid Cyanobacterium. AB - The glycosylated and halogenated dialkylresorcinol (DAR) compounds bartolosides A D (1-4) were recently discovered from marine cyanobacteria and represent a novel family of glycolipids, encoded by the brt biosynthetic gene cluster. Here, we report the isolation and NMR- and MS-based structure elucidation of monoglycosylated bartolosides E-K (5-11), obtained from Synechocystis salina LEGE 06099, a strain closely related to the cyanobacterium that produces the diglycosylated 2-4. In addition, a genome region containing orthologues of brt genes was identified in this cyanobacterium. Interestingly, the major bartoloside in S. salina LEGE 06099 was 1 (above 0.5% dry wt), originally isolated from the phylogenetically distant filamentous cyanobacterium Nodosilinea sp. LEGE 06102. Compounds 5-11 are analogues of 1, with different alkyl chain lengths or halogenation patterns. Their structures and the organization of the brt genes suggest that the DAR-forming ketosynthase BrtD can generate structural diversity by accepting fatty acyl-derived substrates of varying length. Compound 9 features a rare midchain gem-dichloro moiety, indicating that the putative halogenase BrtJ is able to act twice on the same midchain carbon. PMID- 27680199 TI - Piecing together the stunting puzzle: a framework for attributable factors of child stunting. AB - Reducing the burden of stunting in childhood is critical to improving health in low- and middle-income settings. However, because many aetiologies underlie linear growth failure, stunting has proved difficult to prevent and reverse. Understanding the contributions these aetiologies make to the burden of stunting can help the development of targeted, effective interventions. To begin to frame these causes, a qualitative and a quantitative framework of the primary drivers of stunting in low-resource settings were developed. Population attributable fractions (PAF) were estimated to inform the quantitative framework. According to these estimates, infectious diseases were responsible for large attributable fractions in all settings, and a combination of dietary indicators also comprised a large fraction in Africa. However, the PAF calculation was found to have several limitations, including a requirement for a binary outcome and sensitivity to confounding, which necessitate broad interpretation of the results. More robust tools to model complex causality are needed in order to understand the causal aetiology of stunting. PMID- 27680201 TI - Multiphase Ozonolysis of Aqueous alpha-Terpineol. AB - Multiphase ozonolysis of aqueous organics presents a potential pathway for the formation of aqueous secondary organic aerosol (aqSOA). We investigated the multiphase ozonolysis of alpha-terpineol, an oxygenated derivative of limonene, and found that the reaction products and kinetics differ from the gas-phase ozonolysis of alpha-terpineol. One- and two-dimensional NMR spectroscopies along with GC-MS identified the aqueous ozonolysis reaction products as trans- and cis lactols [4-(5-hydroxy-2,2-dimethyltetrahydrofuran-3-yl)butan-2-one] and a lactone [4-hydroxy-4-methyl-3-(3-oxobutyl)-valeric acid gamma-lactone], which accounted for 46%, 27%, and 20% of the observed products, respectively. Hydrogen peroxide was also formed in 10% yield consistent with a mechanism involving decomposition of hydroxyl hydroperoxide intermediates followed by hemiacetal ring closure. Multiphase reaction kinetics at gaseous ozone concentrations of 131, 480, and 965 parts-per-billion were analyzed using a resistance model of net ozone uptake and found the second-order rate coefficient for the aqueous reaction of alpha terpineol + O3 to be 9.9(+/-3.3) * 106 M-1 s-1. Multiphase ozonolysis will therefore be competitive with multiphase oxidation by hydroxyl radicals (OH) and ozonolysis of gaseous alpha-terpineol. We also measured product yields for the heterogeneous ozonolysis of alpha-terpineol adsorbed on glass, NaCl, and kaolinite, and identified the same three major products but with an increasing lactone yield of 33, 49, and 55% on these substrates, respectively. PMID- 27680202 TI - Synthesis of Allylic Amide Functionalized 2H-Chromenes and Coumarins Using a One Pot Overman Rearrangement and Gold(I)-Catalyzed Hydroarylation. AB - A four-step synthesis of allylic trichloroacetimidates bearing a 2 proparyloxyaryl group has been developed from readily available 2 hydroxybenzaldehydes, and these have been used for the preparation of allylic amide derived 2H-chromenes using an Overman rearrangement and a 6-endo-dig hydroarylation. High yields of the 2H-chromenes were achieved using a stepwise approach involving an Overman rearrangement under thermal conditions followed by a hydroarylation reaction with a gold(I) triflimide catalyst. An alternative method where both reactions were performed as a one-pot process was also developed and instead used a gold(I) chloride catalyst activated by silver(I) hexafluoroantimonate for the cycloisomerization step. The allylic amide derived 2H-chromenes were converted to the corresponding coumarin analogues by a pyridinium dichromate (PDC)-mediated chemoselective allylic oxidation. PMID- 27680203 TI - Commentary : Hypothesis Focused Ultrasound and NXY-059 in Experimental Cerebral Ischemia: A New Therapeutic Opportunity? PMID- 27680205 TI - Comment on the Comment on "Ultrahigh Performance Supercapacitor from Lacey Reduced Graphene Oxide Nanoribbons". PMID- 27680204 TI - Editorial: (Thematic Issue) Novel Concepts on the Blood-Brain Barrier and Brain Pathology. New Therapeutic Approaches. PMID- 27680206 TI - Perinatal health care services for imprisoned pregnant women and associated outcomes: a systematic review. AB - BACKGROUND: Women are an increasing minority of prisoners worldwide, and most are of childbearing age. Prisons offer unique opportunities for improving the pregnancy outcomes of these high-risk women, and no systematic review to date has looked at their care. This systematic review identified studies describing models of perinatal health care for imprisoned women which report maternal and child health and care outcomes. METHODS: We systematically searched for literature published between 1980 and April 2014. Studies were eligible if they included a group of imprisoned pregnant women, a description of perinatal health care and any maternal or infant health or care outcomes. Two authors independently extracted data. We described relevant outcomes in prisons (including jails) under models of care we termed PRISON, PRISON+ and PRISON++, depending on the care provided. Where outcomes were available on a comparison group of women, we calculated odds ratios with 95 % confidence intervals. RESULTS: Eighteen studies were reported, comprising 2001 imprisoned pregnant women. Fifteen were in the US, two in the UK and one in Germany. Nine contained a comparison group of women comprising 849 pregnant women. Study quality was variable and outcome reporting was inconsistent. There was some evidence that women in prisons receiving enhanced prison care, PRISON+, were less likely to have inadequate prenatal care (15.4 % vs 30.7 %, p < 0 . 001), preterm delivery (6.4 % vs 19.0 %, p = 0 . 001) or caesarean delivery (12.9 % vs 26.5 %, p = 0 . 005) compared to women in prisons receiving usual care (PRISON). Women participating in two PRISON++ interventions, that is, interventions which included not only enhanced care in prisons but also coordination of community care on release, demonstrated reductions in long term recidivism rates (summary OR 0 . 37, 95 % CI 0 . 19-0 . 70) compared to pregnant women in the same prisons who did not participate in the intervention. CONCLUSIONS: Enhanced perinatal care can improve both short and long-term outcomes but there is a lack of data. Properly designed programmes with rigorous evaluation are needed to address the needs of this vulnerable population. The cost to mothers, children and to society of failing to address these important public health issues are likely to be substantial. TRIAL REGISTRATION: PROSPERO registration: CRD42012002384 . PMID- 27680207 TI - Definition of important early morbidities related to paediatric cardiac surgery. AB - BACKGROUND: Morbidity is defined as a state of being unhealthy or of experiencing an aspect of health that is "generally bad for you", and postoperative morbidity linked to paediatric cardiac surgery encompasses a range of conditions that may impact the patient and are potential targets for quality assurance. METHODS: As part of a wider study, a multi-disciplinary group of professionals aimed to define a list of morbidities linked to paediatric cardiac surgery that was prioritised by a panel reflecting the views of both professionals from a range of disciplines and settings as well as parents and patients. RESULTS: We present a set of definitions of morbidity for use in routine audit after paediatric cardiac surgery. These morbidities are ranked in priority order as acute neurological event, unplanned re-operation, feeding problems, the need for renal support, major adverse cardiac events or never events, extracorporeal life support, necrotising enterocolitis, surgical site of blood stream infection, and prolonged pleural effusion or chylothorax. It is recognised that more than one such morbidity may arise in the same patient and these are referred to as multiple morbidities, except in the case of extracorporeal life support, which is a stand alone constellation of morbidity. CONCLUSIONS: It is feasible to define a range of paediatric cardiac surgical morbidities for use in routine audit that reflects the priorities of both professionals and parents. The impact of these morbidities on the patient and family will be explored prospectively as part of a wider ongoing, multi-centre study. PMID- 27680208 TI - The different effects of probiotics treatment on Salmonella-induced interleukin-8 response in intestinal epithelia cells via PI3K/Akt and NOD2 expression. AB - Salmonella spp. remains a major public health problem for the whole world. Intestinal epithelial cells serve as an essential component of the innate mucosal immune system to defend against Salmonella infection. A substantial amount of evidence has accumulated that probiotics can regulate interleukin 8 (IL-8) involved in innate immunity. However, the exact effect of probiotics on epithelial IL-8 response to Salmonella infection is not well understood. Therefore, we investigated the action of probiotics on Salmonella-infected Caco-2 cells and its novel mechanisms. Two probiotic strains were examined for Salmonella-induced IL-8 responses and regulating proteins using Caco-2 cell cultures. We demonstrated probiotic, either Lactobacillus rhamnosus GG or Bifidobacterium animalis subsp. lactis DSM10140, administered before Salmonella infection conferred significantly suppressive effect on Salmonella-induced IL-8 responses in Caco-2 cells, either in secreted protein or mRNA, via the PI3K/Akt signal pathway while probiotic administered after infection enhanced Salmonella induced IL-8 responses via nucleotide-binding oligomerisation domain-containing protein 2 expression in membrane. These findings suggest that the different regulation of probiotics on Salmonella-induced IL-8 responses in Caco-2 cells according to the administered timing supports a rationale for the therapeutic use of probiotics in the treatment of Salmonella colitis and inflammatory bowel disease. This can explain the reported controversial effect of probiotics on these diseases. PMID- 27680209 TI - Feed supplementation with avian Propionibacterium acidipropionici contributes to mucosa development in early stages of rearing broiler chickens. AB - Different studies in animal rearing claim the probiotic potential of species of the genus Propionibacterium. The effects of strains of Propionibacterium acidipropionici isolated from poultry intestine on microbiota activity and intestinal mucosa development were investigated in the early stage of rearing chicks and the safety of the dose used was investigated. The strains P. acidipropionici LET105 and LET107, administered as monoculture to chicks from the 1st to 14th day of life in a daily dose of 106 cfu/ml administered in the drinking water resulted harmless. The animals arrived at the expected weight for age and no differences were observed with respect to the food intake and water consumption related to control without bacteria administration. The analysis of microbiota composition revealed the presence of propionibacteria at the middle and end of the trial only in treated groups. Normal development of lactic acid bacteria and bifidobacteria, and slow colonisation by Bacteroides at the 7th day of the study was observed in the same groups. Analysis of the organic acids concentrations in the caecal content of birds revealed higher lactic acid and lower butyric acid production. Lower short chain fatty acids total concentration than expected during treatment was related to a better development of the gut mucosa. Increase in length of villus-crypt units, goblet cells counts and neutral mucins production were evidenced. Higher mucus secretion produced by dietary supplementation with propionibacteria could provide increased protection against pathogens. PMID- 27680210 TI - Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia. AB - BACKGROUND: Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX(r), have the potential to promote a full range of events leading to tissue regeneration and homeostasis. The main goal of this work was to investigate UCX(r) action in experimentally induced hindlimb ischemia (HLI). METHODS: UCX(r), obtained by using a proprietary technology developed by ECBio (Amadora, Portugal), were delivered via intramuscular injection to C57BL/6 females after unilateral HLI induction. Perfusion recovery, capillary and collateral density increase were evaluated by laser doppler, CD31 immunohistochemistry and diaphonisation, respectively. The activation state of endothelial cells (ECs) was analysed after EC isolation by laser capture microdissection microscopy followed by RNA extraction, cDNA synthesis and quantitative RT-PCR analysis. The UCX(r)-conditioned medium was analysed on Gallios flow cytometer. The capacity of UCX(r) in promoting tubulogenesis and EC migration was assessed by matrigel tubule formation and wound-healing assay, respectively. RESULTS: We demonstrated that UCX(r) enhance angiogenesis in vitro via a paracrine effect. Importantly, after HLI induction, UCX(r) improve blood perfusion by stimulating angiogenesis and arteriogenesis. This is achieved through a new mechanism in which durable and simultaneous upregulation of transforming growth factor beta2, angiopoietin 2, fibroblast growth factor 2, and hepatocyte growth factor, in endothelial cells is induced by UCX(r). CONCLUSIONS: In conclusion, our data demonstrate that UCX(r) improve the angiogenic potency of endothelial cells in the murine ischemic limb suggesting the potential of UCX(r) as a new therapeutic tool for critical limb ischemia. PMID- 27680211 TI - Critical neural targets for (the level of) human consciousness: Arousal arrest and unconsciousness after sumatriptan administration. AB - BACKGROUND: Insufficient understanding of the mechanisms of consciousness can make unconsciousness a diagnostic challenge, directly effecting the treatment and the outcome of the patient. Consciousness is a product of brainstem arousal (wakefulness, the level of consciousness) and cortical information integration (awareness, the contents of consciousness). The thalamus serves as a critical hub in the arousal pathway. The nuclei within the internal medullary lamina, together with the associated thalamocortical connections, have been implicated as being especially important for human consciousness. CASE STUDY: A 17-year old male migraineur developed a sudden episode of unconsciousness after receiving a single dose of intranasal sumatriptan for the treatment of prolonged migraine-associated symptoms. Diffusion-weighted magnetic resonance imaging revealed a small bilateral thalamic infarction affecting the centromedian and parafascicular nuclei and the associated non-specific thalamocortical connections as the likely reason for the impairment of consciousness. With the exception of occasional fatigue due to a persistent lesion on the left thalamus, the patient experienced full recovery. Corresponding to the injury, diffusion tensor tractography imaging revealed a distinctive defect on the thalamocortical fibres originating from the left centromedian/parafascicular nuclei complex. CONCLUSIONS: The presented case offers an outstanding example of the importance of the arousal system and non specific thalamocortical connectivity for normal waking consciousness. PMID- 27680213 TI - Update on Brazilian biosimilar enoxaparins. AB - INTRODUCTION: Brazil is among the first countries approving the commercialization and clinical use of biosimilar enoxaparins. Our research group has performed quality control assessments of these drugs over the last decade. Areas covered: We have not found noticeable differences between Brazilian biosimilar enoxaparins and the original product regarding their physicochemical properties, disaccharide composition, anticoagulant activity, bioavailability and safety. Expert commentary: In spite of clinical and pharmacological advantages of enoxaparin, subcutaneous formulations of unfractionated heparin are employed by the Brazilian public health system for prevention and treatment of thromboembolism. The underuse of both original and biosimilar enoxaparins in Brazil directly correlates with their high cost. PMID- 27680212 TI - Arterial stiffness in hypertensive and type 2 diabetes patients in Ghana: comparison of the cardio-ankle vascular index and central aortic techniques. AB - BACKGROUND: Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither. METHOD: Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart-ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured. RESULTS: In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean +/- SD, 8.3 +/- 1.2 vs 7.5 +/- 1.1 and 7.4 +/- 1.1 units; p < 0.05), PWVao (9.1 +/- 1.4 vs 8.7 +/- 1.9 and 8.1 +/- 0.9 m/s; p < 0.05) and haPWV (8.5 +/- 1 vs 7.9 +/- 1 and 7.2 +/- 0.7 m/s; p < 0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (beta = 0.49, 0.2, 0.17 and -0.2 units; p < 0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (beta = 0.42, 0.27 and 0.22; p < 0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (beta = 0.46, 0.32, -0.2, 0.2 and 0.11; p < 0.01). CONCLUSION: In this sub Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention. PMID- 27680215 TI - Towards a unified and standardized definition of the frailty phenotype. PMID- 27680216 TI - Severe lower urinary tract symptoms due to anteriorly located midline prostatic cyst arising from the bladder neck in a young male: case report. AB - CONTEXT:: Prostatic cysts are uncommon. These cysts are usually asymptomatic and are diagnosed incidentally during ultrasonographic examination. On rare occasions, they may cause drastic symptoms. CASE REPORT:: We report on a case of severely symptomatic anteriorly located prostatic cyst arising from the bladder neck in a 30-year-old man presenting with lower urinary tract symptoms, without clinical evidence of benign prostatic hyperplasia. Transrectal ultrasonography (TRUS), computed tomography (CT) and cystourethroscopy demonstrated a projecting prostatic cyst that occupied the bladder neck at the precise twelve o'clock position. It was acting as a ball-valve, such that it obstructed the bladder outlet. Transurethral unroofing of the cyst was performed and the patient's obstructive symptoms were successfully resolved. Histopathological examination indicated a retention cyst. CONCLUSIONS:: It should be borne in mind that midline prostate cysts can be a reason for bladder outlet obstruction in a young male. Such patients may have tremendous improvement in symptoms through transurethral unroofing of the cyst wall. PMID- 27680214 TI - Cellular effects induced by 17-beta-estradiol to reduce the survival of renal cell carcinoma cells. AB - BACKGROUND: Renal cell carcinoma (RCC) is an adult malignancy with 2:1 men-to women ratio, which implies the possible role of sex hormones in RCC carcinogenesis. One of the predominant sex hormones in women before menopause, 17 beta-estradiol (or E2), may regulate RCC growth by cellular mechanisms that are still not fully understood. METHODS: The expression levels of E2 receptors (ER1 and ER2) were determined in different RCC cell lines. The DNA damage response induced by E2 was determined by a DNA double-strand break marker gammaH2AX. To study the possible effect of E2 on oxidative stress response, RCC cells were stained with 2,7-dichlorofluorescein diacetate and analyzed by flow cytometry. Upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) ser40 phosphorylation in response to oxidative stress was detected by immunoblotting. Finally, annexin V/propidium iodide (PI) double staining assay was used to determine E2-induced cellular apoptosis. RESULTS: Variable expression of ER1 and ER2 were found in the RCC cell lines studied (786-O, A498, and ACHN), in which ACHN and A498 showed highest and lowest ER expression, respectively. In A498 cells, E2 induced DNA double-strand breaks with positive staining of gammaH2AX. On the other hand, the level of reactive oxidative species were elevated in ACHN cells after E2 treatment. The E2-induced oxidative stress also induced the Ser40 phosphorylation and nuclear translocation of Nrf2. Finally, we also demonstrated that E2 induced apoptosis as revealed by annexin V/PI double staining. CONCLUSIONS: In this study, we demonstrated the cellular effects of E2 on DNA repair, ROS production as well as Nrf2 activation, and apoptosis in RCC cell lines. Together these cellular alterations may contribute to the reduced viability of RCC cells following E2 treatment. PMID- 27680217 TI - Frequency of pain and eating disorders among professional and amateur dancers. AB - CONTEXT AND OBJECTIVE:: The pursuit of perfection can cause anxiety and lead dancers to exceed their physical limits. The aim here was to evaluate the prevalence of pain symptoms and eating disorders among professional and amateur dancers. DESIGN AND SETTING:: Observational cross-sectional study; Curitiba, PR, Brazil. METHODS:: Data on 150 professional and non-professional practitioners of ballet, jazz and street dance were collected through specific questionnaires: Brief Pain Inventory-Short Form (BPI-SF), Eating Attitudes Test-26 (EAT-26), Bulimic Investigatory Test Edinburgh (BITE) and State-Trait Anxiety Inventory-T-6 (STAI-T-6). RESULTS:: Pain was observed in 58.6% of the sample, equally between professionals and amateurs (P = 0.19). Ballet dancers had more lower-limb pain than the other groups (P = 0.05). EAT-26 showed a tendency towards more eating disorders among the amateurs (P = 0.06). Higher risk of eating disorders was found among ballet dancers (P = 0.004) and jazz practitioners (P = 0.02) than among street dancers. Amateurs had more symptoms on the BITE scale (P < 0.0001), more pain (P = 0.002) and higher anxiety (P < 0.0001). Eating disorders were more common among females (P = 0.01) and singles (P = 0.02). Professionals were more satisfied with their own body image than amateurs (P < 0.001). CONCLUSIONS:: Pain symptoms were found in almost half of the sample, equally among professionals and amateurs as well as between the three dance styles. Female and singles had more eating disorders. Those with eating disorders had higher levels of pain and anxiety. PMID- 27680218 TI - Translation to Brazilian Portuguese, cultural adaptation and reproducibility of the questionnaire "Ankylosing Spondylitis: What do you know?" AB - CONTEXT AND OBJECTIVE:: Ankylosing spondylitis (AS) generates inflammation and pain in entheses, peripheral joints and the spine. Education regarding AS can improve patients' disability. Thus, it is important to assess patients' knowledge. There is no instrument in the literature for assessing knowledge of AS in Portuguese. The aim here was to translate to the Brazilian Portuguese language, culturally adapt and test the reliability of the questionnaire "Ankylosing Spondylitis: What do you know?" and to correlate the findings with other factors. DESIGN AND SETTING:: Original article regarding validation of questionnaire, produced at the Federal University of Sao Paulo (Unifesp). METHODS:: For translation and cultural adaptation, Guilleman methodology was used. After the first phase, the reliability was tested on 30 patients. Correlations between these scores and other factors were examined. RESULTS:: In the interobserver assessment, the Pearson correlation coefficient and Cronbach's alpha were 0.831 and 0.895, respectively. In the intraobserver evaluation, the intraclass correlation coefficient and Cronbach's alpha were 0.79 and 0.883, respectively. At this stage, the score for area of knowledge A showed correlations with ethnicity and education; the score for area D, with age; the total score and scores for areas A and B with "social aspects" of SF-36; and the score for area D with "pain", "vitality" and "emotional aspects" of SF-36. CONCLUSION:: The Brazilian version of the questionnaire "Ankylosing Spondylitis: What do you know?" was created. It is reproducible and correlates with education level, ethnicity and the SF-36 domains "social aspects" and "emotional aspects". PMID- 27680219 TI - A randomised half body prospective study of low and medium dose regimens using the 308 nm excimer laser in the treatment of localised psoriasis. AB - This study compared two dose-escalation regimens using the 308 nm excimer laser treating localised plaque psoriasis, to determine the optimal regimen. A randomised, left-right body trial was designed including patients aged >18 years with localised plaque psoriasis (<10% body surface area). The standard/low dose regimen started at 70% of the minimal erythema dose (MED), with 20% dose increments. The medium dose regimen commenced at 200% MED, with 25% increments. Patients were treated until disease clearance or a maximum of 36 treatments. Fifteen patients aged 28-55 years completed the study. Psoriasis severity index scores analysed at weeks 0, 6 and 12 showed a significant reduction with each regimen (p < 0.0001). Six patients cleared, seven had significant improvement with uneven clearance of plaques and two failed. Average remission was four months (range 1-12 months). There was a significant reduction in DLQI (p = 0.014). Excimer laser improved psoriasis and reduced DLQI scores, but clearance was incomplete for many patients and remission was short-lived. Adverse effects of pain and blistering were commoner with the medium dose regimen, without any benefit in psoriasis clearance. PMID- 27680220 TI - Successful surgical resection of solitary plasmacytoma of the liver mimicking hepatocellular carcinoma. A case report. AB - : Solitary extramedullary plasmacitomas (SEMP) of the liver are very rare. We report the case of an elderly woman with a huge symptomatic SEMP of the liver mimicking hepatocellular carcinoma (HCC). The patient was a 89-year-old woman who presented with severe abdominal pain and a huge solid mass in the right hypochondrium. The laboratory data on admission revealed normal liver function tests. A multiphasic computed tomography (CT) showed a huge solid mass of the left hemiliver, hypoattenuating on noncontrast images, dishomogeneously hyperenhancing in the late arterial phase, with washout in the portal venous and equilibrium phases. A 18F-FDG positron emission tomography (18F-FDG PET)-CT scan documented a marked FDG uptake within the lesion, without evidence of extrahepatic metastases. We considered the clinical and radiologic findings consistent with the diagnosis of high-grade HCC with areas of intratumoral necrosis preluding to possible tumour rupture. Surgical resection was ultimately considered feasible with a reasonable risk and the patient underwent left hepatectomy with diaphragmatic resection. Pathological examination exhibited an extramedullary plasmacytoma. At immunohistochemical analysis neoplastic cells were positive for CD45, CD38, IRF4, HTPD52, kappa-chain, but negative for lambda- chain; Mib-1 proliferation index was 50%. Subsequent clinical evaluation excluded any sign of multiple myeloma, so that a diagnosis of truly localized SEMP of the liver was finally established. To our knowledge, this is the first case of a solitary extramedullary plasmacitoma of the liver undergoing successful radical liver resection. The patient is alive and well 5 years after surgery without evidence of local recurrence and of systemic disease. KEY WORDS: Extramedullary plasmacytoma, Hepatocellular carcinoma, Liver, Liver resection, Multiple myeloma. PMID- 27680221 TI - A case of cerebrotendinous xanthomatosis mimicking the clinical phenotype of mitochondrial disease with a novel frame-shift mutation (c. 43_44 delGG) in CYP27A1 gene exon 1. AB - A 37-old-male with a history of early childhood mental retardation was admitted to our hospital. He experienced recurrent syncopes at 23 years old, and at age 35 gait disturbance and hearing impairment developed gradually and worsened over time. His grandparents were in a consanguineous marriage. He was of short stature and absent of tendon xanthomas. Neurological examinations revealed scanning speech, dysphagia, right sensorineural hearing loss, spasticity in both upper and lower extremities, and spastic gait. Tendon reflexes were brisk throughout, and Babinski and Chaddock reflexes were both positive bilaterally. Laboratory tests revealed elevated lactate and pyruvate concentrations in both serum and cerebrospinal fluid. Fluid attenuated inversion recovery magnetic resonance imaging showed high intensity lesions in the bilateral cerebellar hemispheres, pyramidal tracts in the brainstem, and internal capsules symmetrically. Brain magnetic resonance spectroscopy measurements revealed an elevated lactate/creatine plus phosphocreatine ratio and a decreased N-acetyl aspartate/creatine plus phosphocreatine ratio in the cerebellum. At this point, mitochondrial diseases, particularly myoclonic epilepsy with ragged-red fibers (MERRF), to be the most likely cause. We performed a biopsy of his left biceps brachii muscle, showing variations in fiber size with occasional central nuclei and very few ragged-red fibers. Blood mitochondrial respiratory enzyme assays showed normal values with elevated citrate synthase activity, and mitochondrial DNA analyses for MERRF revealed no pathogenic mutations. We then explored other possibilities and detected an elevated serum cholestanol concentration of 20.4 MUg/ml (reference value <4.0) and genetic analysis by direct sequencing method disclosed a novel frame-shift mutation (c. 43_44delGG) in CYP27A1 gene exon1, leading to a diagnosis of cerebrotendinous xanthomatosis (CTX). This case emphasizes importance of awareness of CTX as a possibility when patients present with clinical phenotypes mimicking mitochondrial diseases, but with negative results for muscle pathology or genetic analyses. The measurements of serum cholestanol concentrations might be useful in diagnosing such atypical cases. PMID- 27680222 TI - An overlap case of Fisher syndrome and pharyngeal-cervical-brachial variant of Guillain-Barre syndrome associated with urinary retention and constipation. AB - We report a 28-year-old woman with the overlap of Fisher syndrome and pharyngeal cervical-brachial variant of Guillain-Barre syndrome associated with urinary retention and constipation. She showed total ophthalmoplegia, dysphagia, dysarthria, upper extremity weakness, cerebellar ataxia, slightly diminished superficial sensations in her hands and feet, urinary retention and constipation 14 days after preceding infection. Laboratory data showed elevations of antiganglioside antibodies to GT1b, GD1b, GQ1b, GD3 and GT1a in the IgG subclass. There was slight elevation of protein with no pleocytosis in cerebrospinal fluid. After administration of intravenous immunoglobulin (IVIg), only the titer of antiganglioside antibody to GQ1b was decreased, and she showed rapid improvement in dysphagia, urinary retention and constipation, and slow recovery in ophthalmoplegia and cerebellar ataxia. The elevations of antiganglioside antibodies to GQ1b may be pathologically related to autonomic involvement such as urinary retention and constipation in that IVIg seems to be effective. The present case suggests that GQ1b may also locate in the autonomic nerve that plays bladder and defecation functions, and that incidence of neurological symptoms and the response of treatment may differ according to each GQ1b localization. PMID- 27680223 TI - A case of chronic inflammatory demyelinating polyradiculoneuropathy after treatment with pegylated interferon alpha-2a in a patient with chronic hepatitis B virus infection. AB - We report the case of a 42-year-old man with chronic hepatitis B virus infection who developed weakness and paresthesia in the extremities 2 months after administration of pegylated interferon (Peg-IFN)alpha-2a. Nerve conduction studies conducted 6 months after onset showed abnormal temporal dispersions in both tibial nerves. We diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) resulting from treatment with Peg-IFNalpha-2a. Neurological symptoms were prolonged despite suspension of the treatment. Subsequent treatment with intravenous immunoglobulin improved both clinical symptoms and temporal dispersion. IFNalpha-induced CIDP is rare, but can reportedly progress even after interruption of IFN-alpha without immunotherapy. Patients presenting with polyneuropathy after initiation of IFN-alpha thus require close attention. PMID- 27680224 TI - A case of Cefepime encephalopathy, being difficult to distinguish from non convulsive status epilepticus during the treatment of bacterial meningitis. AB - A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients. PMID- 27680225 TI - A case of intravenous immunoglobulin-dependent chronic inflammatory demyelinating polyneuropathy of pure motor form responsive to mycophenolate mofetil therapy. AB - This report concerns a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with frequent treatment-dependent relapses. A 75 year-old male presented with a 2-month history of progressive weakness of the limbs with no sensory symptoms. Neurological examination revealed normal cranial nerves, MRC grade 4 power in the proximal and distal muscles of the limbs, and generalized areflexia. However, the sensory examination results, serum immunoelectrophoresis, anti-HIV antibody, and vitamins B1 and B12 levels were normal. Cervical MR imaging was unremarkable. Cerebrospinal fluid showed albuminocytologic dissociation. Nerve conduction studies demonstrated prolonged distal latencies in the bilateral median nerves and left ulnar nerve. Treatment with intravenous immunoglobulin (IVIg) infusion resulted in a marked improvement. Thereafter, the patient had been treated with repeated IVIg to maintain motor function. Subsequently, the patient fulfilled the EFNS/PNS diagnostic criteria for pure motor form of definite CIDP. Treatment with ciclosporin with the plasma trough level of 60-150 ng/ml reduced the frequency of IVIg. However, renal function began to deteriorate 94 months after the initiation of ciclosporin. The calcineurin inhibitor was replaced with mycophenolate mofetil 1,500 mg, which significantly increased the interval between infusions without further renal impairment. Therefore, mycophenolate may represent an effective alternative treatment for some IVIg-dependent CIDP patients. PMID- 27680226 TI - Fisher syndrome with delayed facial weakness and taste impairment: a case report. AB - A 55-year-old man was admitted to our hospital because of acute onset of diplopia and gait disturbance. On admission, ophthalmoplegia, ataxia and areflexia were observed. He was diagnosed with Fisher syndrome and given intravenous immunoglobulin therapy from day 6 to day 10 after disease onset. After treatment, ophthalmoplegia and ataxia began to improve. However, he developed taste impairment on day 13 and right hemifacial weakness on day 16 after onset. A blink reflex test revealed right facial nerve impairment. On day 42 after onset, facial weakness and taste impairment remitted, and the blink reflex test result was normalized without additional treatment. Although it has been known that 10% of patients with Fisher syndrome complicated by delayed facial nerve palsy, the mechanism of the facial nerve palsy has not been elucidated. Therefore, this is a significant report to describe delayed facial nerve palsy combined with taste impairment and successive recordings of blink reflex and facial nerve conduction in a patient with Fisher syndrome. PMID- 27680227 TI - A year of triumph. AB - There have been troubled and triumphant times for nurses in 1991. A year of change, of success and celebration. Nursing has achieved a great deal over the past 12 months. It has increased its academic standing, more Project 2000 courses have come on stream, prescribing powers for community nurses are finally within our grasp and the UK Central Council's proposals for Post-registration Education and Practice (PREP) have come to fruition. Nursing has also received a significant boost with the extra L3.2 million for nursing development units and the concept of the 'named nurse' for every patient incorporated into the Patient's Charter. PMID- 27680228 TI - System not geared to patients' needs. AB - Britain's prison hospitals are facing a major shake-up amid accusations of substandard care, filthy conditions and overuse of psychiatric drugs. PMID- 27680229 TI - Review body on pay. AB - The futureof the nurses' pay Review body remains uncertain, following Health Secretary William Waldegrave's comments in a Nursing Standard interview last week. PMID- 27680230 TI - New community charter to be launched in 1992. AB - A new charter to tackle the 'bloody mess' of community health services will be launched next year, RCN President Professor June Clark has announced. PMID- 27680231 TI - Confusion over 'do not resuscitate'. AB - Nurses are making 'wrong' life and death resuscitation decisions because doctors are not communicating with them properly, a new survey has warned. PMID- 27680233 TI - New living-in rules compared to 'apartheid'. AB - New rules to improve junior doctors' accommodation are forcing student nurses into costly private housing. PMID- 27680234 TI - L170,000 is awarded to nurse for back injury. AB - An enrolled nurse has won over L170,000 compensation fora back injury sustained while using an 'approved' lifting technique. PMID- 27680235 TI - Duplication of training skills requires guidance. AB - A national working group of nurses and junior doctors has been formed to set guidelines for practice and training in areas common to both professions. PMID- 27680237 TI - Key role for nurses as change agents. AB - Nurses must tackle environmental problems inside and outside the profession, the conference was told. PMID- 27680236 TI - Nurse tutors urged to include Green issues. AB - Nurse tutors must include environmental issues in their occupational health teaching if nursing's voice is not to be ignored, an American educator told the conference. PMID- 27680238 TI - Workers' health under threat after cut-backs. AB - Workers' health is being jeopardised by recession-hit companies' cutting back on occupational health expenditure, RCN General Secretary Christine Hancock has warned. PMID- 27680239 TI - ? AB - The world at their hands: Sunderland health visitor Carole Elliott (left) and Birmingham nurse counsellor Lilieth Smith received L5.000 travel scholarships to visit Bangladesh and the West Indies from TV personality Robert Elms. The awards were sponsored by the Royal National Pension Fund for Nurses and the RCN. PMID- 27680240 TI - Blanket payment for services suggested. AB - Item-for-service payments to GPs providing maternity care must be replaced by a capitation system to avoid duplication of services, the Royal College of Midwives has declared. PMID- 27680242 TI - Angry demonstration follows 'racist comments'. AB - Racist comments attributed to a health service manager in a national newspaper sparked an angry COHSE demonstration outside a London hospital last week. PMID- 27680243 TI - ? AB - School of Wales: Ten Welsh nurses have successfully passed the module in 'Care in management of persons with AIDS and HIV-related conditions', taught at the Royal College of Nursing's Ty Maeth Welsh Board headquarters. The next module begins in January . It gives holders one credit towards the Welsh National Board's continuing education certificate in Professional Practice. PMID- 27680241 TI - NHS Trusts. AB - A COHSE reporton Trusts claims seven months of 'financial mismanagement' have produced cuts in jobs and services, and 'rich rewards' for top managers. PMID- 27680244 TI - Health screening. AB - The Governmentwill make L30 million available next year to expand day surgery units and provide extra whole-body scanners, Health Secretary William Waldegrave announced. PMID- 27680245 TI - MP disappoints breast conference audience. AB - Conservative MP Emma Nicholson's failure to attend the Royal College of Nursing's Breast Care Nursing Society conference prompted calls for a letter to her expressing the audience's disappointment. PMID- 27680246 TI - Government advice ignores links with poverty. AB - New Government advice on avoiding cot death ignores poverty as an important risk factor, the Health Visitors' Association has claimed. PMID- 27680247 TI - Are hospitals elderly to go pressing private? AB - A Commons inquiry is studying allegations that elderly people are being 'pressured' to move from National Health Service hospitals into private nursing homes. PMID- 27680248 TI - World news. AB - CanadaNurses in Quebec claim the profession is at last getting its due. PMID- 27680250 TI - ? AB - Helen Taylor-Thompson, Chair of the Board of Governors at the Mildmay Mission Hospital in East London, helped to launch a fund-raising appeal to run throughout 1992. its centenary year. PMID- 27680251 TI - Malnutrition and elderly people. AB - Vigilant observation of elderly people on admission to long-term care is urged in new research looking at malnutrition in elderly patients. PMID- 27680252 TI - Mismanagement of chronic leg ulcers. AB - Chronic leg ulcers are commonly mismanaged in the NHS and are a major burden for district nurses, the Consumers' Association has warned. It says such ulcers waste outpatient appointments and block beds. PMID- 27680254 TI - Waldegrave on nursing. AB - Q Do you agree with the theories put forward by NHS Director of Personnel Eric Caines on what are nursing and non-nursing tasks'? PMID- 27680253 TI - Suicides up following transfer restrictions. AB - Severe restrictions on the transfer of mentally disturbed prisoners to psychiatric hospitals in Auckland have resulted in a six-fold increase in prison suicides, research shows. PMID- 27680255 TI - That was the year that was... AB - January It was a grim start to the New Year with the Gulf crisis dominating the headlines and medical reservists being called up to join the British forces gathering in the desert. Scottish nurse Henry Power won his battle against the draft on a technicality, having declared that he would rather go to jail. In the build up to the outbreak of war with Iraq, the nursing profession went on red alert. Hospitals throughout the country prepared for the many anticipated casualties and the UKCC launched a 24-hour emergency service to give employers instant confirmation of volunteer nurses' qualifications. Nursing Standard made national news bulletins after publishing, in full, 'confidential' Department of Health clinical guidance on dealing with possible war casualties. The department had sent the information only to regional directors of public health. PMID- 27680256 TI - The A-Z Christmas survival guide. AB - Avoidance Forget it. Unless you've won a slot on Sue Lawley's Desert Island, or you've got a rich relative, you're lumbered. Not even retreating under the duvet will work. After all, you've got to eat, and that means at least one trip to the shops, full of piped Christmas music and people panic buying like Boris Yeltsin's just been made Prime Minister. Accept theAngstand add a relaxation tape to the (growing) shopping list. PMID- 27680257 TI - Christmas in the open air. AB - 'What health problems? I'm bloody fit, me,' said Brian, a homeless man, who is not one to whinge and whine about his health. Brian and his mate 'Bob Dylan', each wearing a couple of T-shirts, a jumper and an overcoat, crack jokes and compete to tell their most gruesome injury tale. It is two weeks before Christmas and they sit, snuggled into a sleeping bag amid the blankets and newspaper sheets of other homeless people who occupy the disused bandstand in London's Lincoln's Inn Fields. They drink one of several cans of extra strong lager and share a cigarette. The weather is freezing and as the sun goes down the wind picks up. The rotting wooden bandstand is the focal point for homeless people in 'the Fields' and, although it's open to the elements, its roof means the ground stays dry. Nearby are three concrete tennis courts where Holborn office workers practise their forehands. The fencing that separates the courts from the green is a support for numerous bashes -cardboard and tarpaulin structures literally bashed together - where more homeless people live. PMID- 27680258 TI - Linking poverty and ill health. AB - Audrey Thompson assesses the links between poverty and ill health by exploring the experiences of key nurses caring for people in the community. PMID- 27680260 TI - Clinical grading: the silver lining? AB - With all the problems that clinical grading has raised can anyone remember the real purpose of it? Our understanding was that it would provide a career development plan that would enable nurses and midwives to develop their potential and clinical skills and allow them to remain involved in clinical practice. PMID- 27680259 TI - Developing a career through nursing. AB - Nurses now seek planned career advancement patterns, as opposed to a series of intermittent, disconnected jobs. Heather-Jane Sears offers practical suggestions on bow they can plan a positive career direction, beginning with an evaluation of personal value systems and lifestyle, and concluding with opportunities that may arise with the advent of the single European Market in 1992. PMID- 27680262 TI - 'We are sisters under the skin'. AB - I have begun to question what motivates me to remain in nursing. PMID- 27680261 TI - Transposition of the great arteries. AB - The transposition of the great arteries is a life- threatening condition affecting infants. This article presents the surgical options for treatment, then describes the nursing care involved in the aftermath of the arterial switch procedure, the preferred intervention at Birmingham Children's Hospital. Research is currently being done to evaluate its success. Although long term follow-up is not yet possible, early results are promising. PMID- 27680263 TI - Concern over NHS reforms. AB - There is increasing concern and dissent over the ethical implications of the NHS reforms, and many doctors and nurses who have chosen to bare their professional consciences now see themselves as dissidents. PMID- 27680264 TI - Casualty Update. AB - Last week's Casualty, which came in with a bang, put men firmly in the wrong. PMID- 27680265 TI - Positive benefits of seclusion. AB - I am writing to support Walter Brennan's argument that seclusion can have positive benefits for patients I ('Alone again, naturally', Nursing Standard November 6) following the Senior Nurse Advisor Brian Topping Morris' letter (Nursing Standard, December 4). PMID- 27680266 TI - Outback lift puts backs out. AB - While we appreciate that Barbara Woodcraft's amusing article 'Uplifting experience?' (Nursing Standard October 30) was intended as a humorous look at a serious problem, we were concerned to see that you accompanied by a photograph of two nurses performing the Australian, or Shoulder lift. PMID- 27680267 TI - Special people. AB - I am writing in response to your article 'It's the patients who take us through' (News features Nursing Standard November 20). PMID- 27680268 TI - Points of view. AB - As a nurse in a small district general hospital, I have been called upon to accompany patients who are being transferred to London hospitals for specialist treatment of conditions such as renal or hepatic failure, acute head injury and ischaemic heart disease. PMID- 27680269 TI - Information exchange. AB - Do any readers have any old picture postcards showing hospital ward scenes in Great Britain between 1900 and 1930? PMID- 27680270 TI - Correction. AB - In 'Living-in fear', (Tradimus Nursing Standard, December 4) Patrick Blundy, Solicitor, Legal Services, Royal College of Nursing, was omitted from the list of authors. This was entirely unintentional. PMID- 27680271 TI - Christmas cheer or drear? AB - I once heard of a man who was given a brand new car for Christmas. PMID- 27680272 TI - Cold comfort for rudolph. AB - Deep in the frozen wilds of Northminster, Santa Waldeclaus peered out of his grotto and stroked his long white beard. The snow lay thick on the ground and he was keen to get on, but the head reindeer had told him gift delivery was suspended. It was the wrong sort of snow. 'My team can't go out in those conditions,' the I head reindeer had said. 'That snow's cold and we can only pull sleighs in warm snow.' PMID- 27680274 TI - Between the lines. PMID- 27680273 TI - Dreams come true in '92? AB - You would have thought any year that resulted in a court judgingCoronation Street'sBill Roache ('Ken Barlow') not boring would have been a significant one perhaps not one of the greats like 1066 or 1945, but certainly a strong candidate for the B team. PMID- 27680275 TI - Christmas fare. PMID- 27680276 TI - Images of '91Every picture tells a story. Beverley Hadfield looks back on seven of the best from the Nursing Standard collection of 1991. PMID- 27680277 TI - Surgical Christmas spirit. AB - The names not Health .... Not on December 24. It's Claus, first name Santa. I'm moonlighting ... undercover, false beard and everything. The sleigh's outside. PMID- 27680278 TI - Modern Manners P J O'Rourke Atlantic Monthly* 280pp $16.95 0-87113-313-X [Formula: see text]. AB - To understand more fully O'Rourke's aim in ModernManners, you have to read the subtitle:An Etiquette Book for Rude People. Because PJ (Patrick Jake, I think) has received more attention on TV, this side of the Atlantic than he has in print. For the December 'Editors' Choice', I chose a look at P J in print. PMID- 27680279 TI - Scream, If You Want To Go Faster H Whyte J Galloway editors Association for Scottish Literary Studies 166pp L5.95 0-948877-12-X [Formula: see text]. AB - Scream, If You Want To Go Faster, an anthology, is Number 9 of the series New Writing Scotland to be produced by the The Association of Scottish Literary Studies (c/o Department of English, University of Aberdeen, AB9 2UB). This particular edition is edited by Hamish Whyte and Janice Galloway, MIND Book of the Year award winner for her first novel The Trick Is To Keep Breathing. PMID- 27680280 TI - Imajica Clive Barker Imajica Harper Collins 854pp L15.99 0-00-223559-5 [Formula: see text]. AB - Mystery, magic and mayhem abound as Clive Barker takes us on a voyage of discovery to the Imajica. PMID- 27680281 TI - Listings. PMID- 27680282 TI - 3D printed alendronate-releasing poly(caprolactone) porous scaffolds enhance osteogenic differentiation and bone formation in rat tibial defects. AB - The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release. In vitro studies showed that MG-63 cells seeded on the Aln/PCL scaffolds displayed increased alkaline phosphatase (ALP) activity and calcium content in a dose-dependent manner when compared with cell cultures in PCL scaffolds. In addition, in vivo animal studies and histologic evaluation showed that Aln/PCL scaffolds implanted in a rat tibial defect model markedly increased new bone formation and mineralized bone tissues in a dose-dependent manner compared to PCL-only scaffolds. Our results show that 3D printed Aln/PCL scaffolds are promising templates for bone tissue engineering applications. PMID- 27680283 TI - Understanding the Relationships Between Inspection Results and Risk of Foodborne Illness in Restaurants. AB - Restaurants are important settings for foodborne disease outbreaks and consumers are increasingly using restaurant inspection results to guide decisions about where to eat. Although public posting of inspection results may lead to improved sanitary practices in the restaurant, the relationship between inspection results and risk of foodborne illness appears to be pathogen specific. To further examine the relationship between inspection results and the risk of foodborne disease outbreaks, we evaluated results of routine inspections conducted in multiple restaurants in a chain (Chain A) that was associated with a large Salmonella outbreak in Illinois. Inspection results were collected from 106 Chain A establishments in eight counties. Forty-six outbreak-associated cases were linked to 23 of these Chain A restaurants. There were no significant differences between the outbreak and nonoutbreak restaurants for overall demerit points or for the number of demerit points attributed to hand washing or cross-contamination. Our analyses strongly suggest that the outbreak resulted from consumption of a contaminated fresh produce item without further amplification within individual restaurants. Inspections at these facilities would be unlikely to detect or predict the foodborne illness outbreak because there are no Food Code items in place to stop the introduction of contaminated food from an otherwise approved commercial food source. The results of our study suggest that the agent and food item pairing and route of transmission must be taken into consideration to improve our understanding of the relationship between inspection results and the risk of foodborne illness in restaurants. PMID- 27680284 TI - Structural and quantum chemical analysis of exciton coupling in homo- and heteroaggregate stacks of merocyanines. AB - Exciton coupling is of fundamental importance and determines functional properties of organic dyes in (opto-)electronic and photovoltaic devices. Here we show that strong exciton coupling is not limited to the situation of equal chromophores as often assumed. Quadruple dye stacks were obtained from two bis(merocyanine) dyes with same or different chromophores, respectively, which dimerize in less-polar solvents resulting in the respective homo- and heteroaggregates. The structures of the quadruple dye stacks were assigned by NMR techniques and unambiguously confirmed by single-crystal X-ray analysis. The heteroaggregate stack formed from the bis(merocyanine) bearing two different chromophores exhibits remarkably different ultraviolet/vis absorption bands compared with those of the homoaggregate of the bis(merocyanine) comprising two identical chromophores. Quantum chemical analysis based on an extension of Kasha's exciton theory appropriately describes the absorption properties of both types of stacks revealing strong exciton coupling also between different chromophores within the heteroaggregate. PMID- 27680285 TI - Blocking Notch signal in myeloid cells alleviates hepatic ischemia reperfusion injury by repressing the activation of NF-kappaB through CYLD. AB - Ischemia-reperfusion (I/R) is a major reason of hepatocyte injury during liver surgery and transplantation. Myeloid cells including macrophages and neutrophils play important roles in sustained tissue inflammation and damage, but the mechanisms regulating myeloid cells activity have been elusive. In this study, we investigate the role of Notch signaling in myeloid cells during hepatic I/R injury by using a mouse model of myeloid specific conditional knockout of RBP-J. Myeloid-specific RBP-J deletion alleviated hepatic I/R injury. RBP-J deletion in myeloid cells decreased hepatocytes apoptosis after hepatic I/R injury. Furthermore, myeloid-specific RBP-J deletion led to attenuated inflammation response in liver after I/R injury. Consistently, Notch blockade reduced the production of inflammatory cytokines by macrophages in vitro. We also found that blocking Notch signaling reduced NF-kappaB activation and increased cylindromatosis (CYLD) expression and knockdown of CYLD rescued reduction of inflammatory cytokines induced by Notch blockade in macrophages during I/R injury in vitro. On the other hand, activation of Notch signaling in macrophages led to increased inflammatory cytokine production and NF-kappaB activation and decreased CYLD expression in vitro. These data suggest that activation of Notch signaling in myeloid cells aggravates I/R injury, by enhancing the inflammation response by NF-kappaB through down regulation of CYLD. PMID- 27680287 TI - The Perceptions of White Clients in a Substance Abuse Program in Which They Are in the Minority. AB - BACKGROUND: There is a large body of literature regarding the need for culturally informed practice with non-white populations in substance abuse treatment. Virtually nothing, however, has been written regarding the needs of white clients when they represent a small minority in treatment programs. OBJECTIVES: The primary purpose of this study is to compare perceptions of treatment and completion rates between white and nonwhite clients in a substance abuse treatment program where white clients represent a small minority. METHODS: In New York City in 2009/2010, at a short-term inpatient program where white clients represented 12% of the population, 611 clients completed surveys that included scales measuring satisfaction, therapeutic alliance, social cohesion, and connection to the program. White and non-white clients were compared regarding results of these scales as well as program completion rates. Furthermore, demographic/background characteristics of the white and nonwhite clients obtained from the surveys were compared. RESULTS: White clients reported lower levels of connection to the treatment program than non-white clients at levels that were statistically significant. However, there were no statistically significant differences between them for the other scales and program completion rates. Although white clients reported greater frequency and number of substances used, they were far less likely to have had felony convictions. CONCLUSIONS: Although differences were not extreme, there was evidence that greater sensitivity to the needs of white clients in programs in which they are in the minority is needed. Furthermore, this study demonstrates racial disparities in criminal justice involvement between white and non-white substance users. PMID- 27680286 TI - Assembling non-ferromagnetic materials to ferromagnetic architectures using metal semiconductor interfaces. AB - In this work, a facile and versatile solution route was used to fabricate room temperature ferromagnetic fish bone-like, pteridophyte-like, poplar flower-like, cotton-like Cu@Cu2O architectures and golfball-like Cu@ZnO architecture. The ferromagnetic origins in these architectures were found to be around metal semiconductor interfaces and defects, and the root cause for their ferromagnetism lay in charge transfer processes from metal Cu to semiconductors Cu2O and ZnO. Owing to different metallization at their interfaces, these architectures exhibited different ferromagnetic behaviors, including coercivity, saturation magnetization as well as magnetic interactions. PMID- 27680289 TI - Negative Relationship between Erythropoietin Dose and Blood Lead Level in Patients Undergoing Maintenance Hemodialysis. AB - The adverse effects of increased blood lead levels have been well discussed. Several antioxidant agents have been reported to offer protection from lead toxicity and to reduce blood lead levels (BLL). Given that erythropoietin (EPO) also has antioxidant properties, the aim of this cross-sectional study was to assess the role of EPO and other clinical variables on BLL in hemodialysis (HD) patients. We recruited 931 maintenance hemodialysis (MHD) patients who had undergone HD for at least 6 months and who had ever received blood lead level (BLL) study. Use of erythropoiesis-stimulating agents followed the The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) Clinical Practice Guideline. We estimated demographic, hematological, nutritional, inflammatory, biochemical, and dialysis-related data based on this study. In the group with EPO, 7% had high BLL. In the group without EPO, 22% had high BLL. From the stepwise liner regression, urban areas, hemodialysis duration, and clearance of urea (KT/Vurea) were positively associated with log BLL. In contrast, diabetes (DM), and monthly EPO dose were negatively associated with log BLL. This study showed that EPO dose might be negatively associated with blood lead levels in patients on maintenance hemodialysis. PMID- 27680291 TI - Mechanical Force-Triggered Drug Delivery. AB - Advanced drug delivery systems (DDS) enhance treatment efficacy of different therapeutics in a dosage, spatial, and/or temporal controlled manner. To date, numerous chemical- or physical-based stimuli-responsive formulations or devices for controlled drug release have been developed. Among them, the emerging mechanical force-based stimulus offers a convenient and robust controlled drug release platform and has attracted increasing attention. The relevant DDS can be activated to promote drug release by different types of mechanical stimuli, including compressive force, tensile force, and shear force as well as indirect formats, remotely triggered by ultrasound and magnetic field. In this review, we provide an overview of recent advances in mechanically activated DDS. The opportunities and challenges regarding clinical translations are also discussed. PMID- 27680292 TI - Large Retropharyngeal Abscesses in an Immunocompetent Adult Patient with Disseminated Tuberculosis. AB - BACKGROUND The retropharyngeal abscess is a rare presentation of head and neck tuberculosis. The pathogenesis of the abscess formation in the retropharyngeal space in the adult is controversial. CASE REPORT We report a case of large retropharyngeal abscesses in a 46-year-old man with disseminated tuberculosis. The patient had severe progressive dysphagia, weight loss, and a slowly enlarging bilateral cervical mass during a period of three months. His posterior pharynx wall was bulging and red, and both tonsils were enlarged and congested. The neck had an abscess of 5 cm in diameter that was firm, tender, and warm along the left sternocleidomastoid muscle. Palpable bilateral lymphadenitis was detected in the submandibular, cervical, axillary, and inguinal regions. A computed tomographic (CT) scan of the neck revealed large bilobulated retropharyngeal abscesses. A liver ultrasound showed multiple hypoechoic lesions. A Ziehl-Neelsen smear for acid-fast bacilli was positive from different abscess samples, and mycobacterial cultures subsequently yielded Mycobacterium tuberculosis. Antituberculous therapy was begun and the retropharyngeal abscesses were aspirated by external incision with complete drainage and relief of symptoms. CONCLUSIONS Large retropharyngeal abscess is a rare entity in which Mycobacterium tuberculosis etiology should be considered, especially in endemic countries, and the diagnosis may be difficult because symptoms and signs are influenced by abscess size and time of onset, or if the etiology is not suspected. PMID- 27680288 TI - Cetylpyridinium chloride mouth rinses alleviate experimental gingivitis by inhibiting dental plaque maturation. AB - Oral rinses containing chemotherapeutic agents, such as cetylpyridinium chloride (CPC), can alleviate plaque-induced gingival infections, but how oral microbiota respond to these treatments in human population remains poorly understood. Via a double-blinded, randomised controlled trial of 91 subjects, the impact of CPC containing oral rinses on supragingival plaque was investigated in experimental gingivitis, where the subjects, after a 21-day period of dental prophylaxis to achieve healthy gingivae, received either CPC rinses or water for 21 days. Within subject temporal dynamics of plaque microbiota and symptoms of gingivitis were profiled via 16S ribosomal DNA gene pyrosequencing and assessment with the Mazza gingival index. Cetylpyridinium chloride conferred gingival benefits, as progression of gingival inflammation resulting from a lack of dental hygiene was significantly slower in the mouth rinse group than in the water group due to inhibition of 17 gingivitis-enriched bacterial genera. Tracking of plaque alpha and beta diversity revealed that CPC treatment prevents acquisition of new taxa that would otherwise accumulate but maintains the original biodiversity of healthy plaques. Furthermore, CPC rinses reduced the size, local connectivity and microbiota-wide connectivity of the bacterial correlation network, particularly for nodes representing gingivitis-enriched taxa. The findings of this study provide mechanistic insights into the impact of oral rinses on the progression and maturation of dental plaque in the natural human population. PMID- 27680293 TI - Optical Devices Constructed from Ferrocene-Modified Microgels for H2O2 Sensing. AB - Ferrocene-modified poly(N-isopropylacrylamide)-based microgels were synthesized, characterized, and used to construct optical devices (etalons). The response of the microgels and etalons to H2O2 was investigated, and we show that both the microgel diameter and the optical properties of the etalons depend on the solution concentration of H2O2 from 0.6 to 35 mM. This behavior is a direct result of the oxidation of ferrocene, which influences the microgel diameter. This was also demonstrated by electrochemical-mediated oxidation/reduction of ferrocene using cyclic voltammetry. We go on to show that these materials could be used to monitor H2O2 that is generated from enzymatic reactions. Specifically, we show that the H2O2 generated from the oxidation of glucose catalyzed by glucose oxidase could be quantified. Finally, the devices can be reused multiple times via a regeneration process. This investigation illustrates the versatility of the etalon system to detect species of broad relevance and how they could potentially be used to quantify products of biological reactions. PMID- 27680290 TI - A novel technique based on in vitro oocyte injection to improve CRISPR/Cas9 gene editing in zebrafish. AB - Contemporary improvements in the type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system offer a convenient way for genome editing in zebrafish. However, the low efficiencies of genome editing and germline transmission require a time-intensive and laborious screening work. Here, we reported a method based on in vitro oocyte storage by injecting oocytes in advance and incubating them in oocyte storage medium to significantly improve the efficiencies of genome editing and germline transmission by in vitro fertilization (IVF) in zebrafish. Compared to conventional methods, the prior micro-injection of zebrafish oocytes improved the efficiency of genome editing, especially for the sgRNAs with low targeting efficiency. Due to high throughputs, simplicity and flexible design, this novel strategy will provide an efficient alternative to increase the speed of generating heritable mutants in zebrafish by using CRISPR/Cas9 system. PMID- 27680294 TI - Detection of Local Tumor Recurrence After Definitive Treatment of Head and Neck Squamous Cell Carcinoma: Histogram Analysis of Dynamic Contrast-Enhanced T1 Weighted Perfusion MRI. AB - OBJECTIVE: This study aimed to explore the added value of histogram analysis of the ratio of initial to final 90-second time-signal intensity AUC (AUCR) for differentiating local tumor recurrence from contrast-enhancing scar on follow-up dynamic contrast-enhanced T1-weighted perfusion MRI of patients treated for head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: AUCR histogram parameters were assessed among tumor recurrence (n = 19) and contrast-enhancing scar (n = 27) at primary sites and compared using the t test. ROC analysis was used to determine the best differentiating parameters. The added value of AUCR histogram parameters was assessed when they were added to inconclusive conventional MRI results. RESULTS: Histogram analysis showed statistically significant differences in the 50th, 75th, and 90th percentiles of the AUCR values between the two groups (p < 0.05). The 90th percentile of the AUCR values (AUCR90) was the best predictor of local tumor recurrence (AUC, 0.77; 95% CI, 0.64-0.91) with an estimated cutoff of 1.02. AUCR90 increased sensitivity by 11.7% over that of conventional MRI alone when added to inconclusive results. CONCLUSION: Histogram analysis of AUCR can improve the diagnostic yield for local tumor recurrence during surveillance after treatment for HNSCC. PMID- 27680295 TI - Evaluating the Relationship between Equilibrium Passive Sampler Uptake and Aquatic Organism Bioaccumulation. AB - This Critcal Review evaluates passive sampler uptake of hydrophobic organic contaminants (HOCs) in water column and interstitial water exposures as a surrogate for organism bioaccumulation. Fifty-seven studies were found where both passive sampler uptake and organism bioaccumulation were measured and 19 of these investigations provided direct comparisons relating passive sampler uptake and organism bioaccumulation. Polymers compared included low-density polyethylene (LDPE), polyoxymethylene (POM), and polydimethylsiloxane (PDMS), and organisms ranged from polychaetes and oligochaetes to bivalves, aquatic insects, and gastropods. Regression equations correlating bioaccumulation (CL) and passive sampler uptake (CPS) were used to assess the strength of observed relationships. Passive sampling based concentrations resulted in log-log predictive relationships, most of which were within one to 2 orders of magnitude of measured bioaccumulation. Mean coefficients of determination (r2) for LDPE, PDMS, and POM were 0.68, 0.76, and 0.58, respectively. For the available raw, untransformed data, the mean ratio of CL and CPS was 10.8 +/- 18.4 (n = 609). Using passive sampling as a surrogate for organism bioaccumulation is viable when biomonitoring organisms are not available. Passive sampling based estimates of bioaccumulation provide useful information for making informed decisions about the bioavailability of HOCs. PMID- 27680296 TI - Early marriage and pregnancy among Syrian adolescent girls in Jordan; do they have a choice? PMID- 27680297 TI - Band Gap Engineering of Two-Dimensional Nitrogene. AB - In our previous study, we have predicted the novel two-dimensional honeycomb monolayers of pnictogen. In particular, the structure and properties of the honeycomb monolayer of nitrogen, which we call nitrogene, are very unusual. In this paper, we make an in-depth investigation of its electronic structure. We find that the band structure of nitrogene can be engineered in several ways: controlling the stacking of monolayers, application of biaxial tensile strain, and application of perpendicular electric field. The band gap of nitrogene is found to decrease with the increasing number of layers. The perpendicular electric field can also reduce the band gap when it is larger than 0.18 V/A, and the gap closes at 0.35 V/A. A nearly linear dependence of the gap on the electric field is found during the process. Application of biaxial strain can decrease the band gap as well, and eventually closes the gap. After the gap-closing, we find six inequivalent Dirac points in the Brillouin zone under the strain between 17% and 28%, and the nitrogene monolayer becomes a Dirac semimetal. These findings suggest that the electronic structure of nitrogene can be modified by several techniques, which makes it a promising candidate for electronic devices. PMID- 27680299 TI - Microwave-Assisted Organocatalytic Intramolecular Knoevenagel/Hetero Diels-Alder Reaction with O-(Arylpropynyloxy)-Salicylaldehydes: Synthesis of Polycyclic Embelin Derivatives. AB - A highly efficient and regioselective approach to new polycyclic embelin derivatives through a domino Knoevenagel condensation/intramolecular hetero Diels Alder reaction using O-(arylpropynyloxy)-salicylaldehydes in the presence of ethylenediamine diacetate (EDDA) is reported. This organocatalyzed protocol is compatible toward a wide range of aryl-substituted alkynyl ethers with electron donating and electron-withdrawing groups. When other active methylene compounds were subjected to this domino reaction the corresponding adducts were obtained in high yield. PMID- 27680298 TI - APOSTL: An Interactive Galaxy Pipeline for Reproducible Analysis of Affinity Proteomics Data. AB - With continuously increasing scale and depth of coverage in affinity proteomics (AP-MS) data, the analysis and visualization is becoming more challenging. A number of tools have been developed to identify high-confidence interactions; however, a cohesive and intuitive pipeline for analysis and visualization is still needed. Here we present Automated Processing of SAINT Templated Layouts (APOSTL), a freely available Galaxy-integrated software suite and analysis pipeline for reproducible, interactive analysis of AP-MS data. APOSTL contains a number of tools woven together using Galaxy workflows, which are intuitive for the user to move from raw data to publication-quality figures within a single interface. APOSTL is an evolving software project with the potential to customize individual analyses with additional Galaxy tools and widgets using the R web application framework, Shiny. The source code, data, and documentation are freely available from GitHub ( https://github.com/bornea/APOSTL ) and other sources. PMID- 27680300 TI - Out of many, one: integrating data in the paediatric cardiovascular environment. AB - Large volumes of data and multiple computing platforms are now universal components of paediatric cardiovascular medicine, but are in a constant state of evolution. Often, multiple sets of related data reside in disconnected "silos", resulting in clinical, administrative, and research activities that may be duplicative, inefficient, and at times inaccurate. Comprehensive and integrated data solutions are needed to facilitate these activities across congenital heart centres. We describe methodology, key considerations, successful use cases, and lessons learnt in developing an integrated data platform across our congenital heart centre. PMID- 27680302 TI - Oncosomes - large and small: what are they, where they came from? PMID- 27680303 TI - [Zoon's balanitis: Correlation between dermatopathology and dermoscopy]. PMID- 27680301 TI - A standardized method to determine the concentration of extracellular vesicles using tunable resistive pulse sensing. AB - BACKGROUND: Understanding the pathogenic role of extracellular vesicles (EVs) in disease and their potential diagnostic and therapeutic utility is extremely reliant on in-depth quantification, measurement and identification of EV sub populations. Quantification of EVs has presented several challenges, predominantly due to the small size of vesicles such as exosomes and the availability of various technologies to measure nanosized particles, each technology having its own limitations. MATERIALS AND METHODS: A standardized methodology to measure the concentration of extracellular vesicles (EVs) has been developed and tested. The method is based on measuring the EV concentration as a function of a defined size range. Blood plasma EVs are isolated and purified using size exclusion columns (qEV) and consecutively measured with tunable resistive pulse sensing (TRPS). Six independent research groups measured liposome and EV samples with the aim to evaluate the developed methodology. Each group measured identical samples using up to 5 nanopores with 3 repeat measurements per pore. Descriptive statistics and unsupervised multivariate data analysis with principal component analysis (PCA) were used to evaluate reproducibility across the groups and to explore and visualise possible patterns and outliers in EV and liposome data sets. RESULTS: PCA revealed good reproducibility within and between laboratories, with few minor outlying samples. Measured mean liposome (not filtered with qEV) and EV (filtered with qEV) concentrations had coefficients of variance of 23.9% and 52.5%, respectively. The increased variance of the EV concentration measurements could be attributed to the use of qEVs and the polydisperse nature of EVs. CONCLUSION: The results of this study demonstrate the feasibility of this standardized methodology to facilitate comparable and reproducible EV concentration measurements. PMID- 27680305 TI - Editorial overview: Molecular and genetic bases of disease. PMID- 27680304 TI - Predictors of HIV-related risk perception and PrEP acceptability among young adult female family planning patients. AB - HIV pre-exposure prophylaxis (PrEP) presents new opportunities for HIV prevention. While women comprise approximately 20% of new HIV infections in the US, significant questions remain about how to most effectively facilitate PrEP uptake for this population. Family planning clinics are a dominant source of health care for young women and support an estimated 4.5 million women annually. We explore characteristics associated with HIV risk perception and PrEP acceptability among young adult women seeking reproductive health services in a high-prevalence setting. A cross-sectional, clinic-based survey was conducted with women ages 18-35 (n = 146) seeking health care at two family planning clinics in the greater Baltimore, Maryland area, from January to April 2014. An estimated 22% of women reported being worried about HIV risk, and 60% reported they would consider taking a pill daily to prevent HIV. In adjusted models, HIV related worry was associated with having no college education, being single or dating more than one person, practicing consistent condom use during vaginal sex, and having ever traded sex. PrEP acceptability was significantly associated with being Black (71% vs. 49%, AOR 2.23, CI: 1.89-2.64) and having ever traded sex (83% vs. 58%, AOR 4.94, CI: 2.00-12.22). For women with a history of intimate partner violence (IPV), PrEP acceptability was significantly lower (57% vs. 62%, AOR .71, CI: .59-.85) relative to their non-abused counterparts. Results suggest that family planning clinics may be a natural setting for PrEP discussion and roll-out. They should be considered in the context of integrating HIV prevention with reproductive health services. Women with a trauma history may need additional support for implementing HIV prevention in the form of PrEP. PMID- 27680306 TI - Natriuretic peptides revisited: new potentials and challenges in heart failure. PMID- 27680308 TI - Reply to: "Statins probably do not cause cataracts". PMID- 27680307 TI - SPECT and fluorescence imaging of vulnerable atherosclerotic plaque with a vascular cell adhesion molecule 1 single-chain antibody fragment. AB - BACKGROUND AND AIMS: Early detection and evaluation of vulnerable atherosclerotic plaque are important for risk stratification and timely intervention, and vascular cell adhesion molecule 1 (VCAM1) assists in adhesion and recruitment of inflammatory cells to vulnerable lesions. We labeled a single-chain variable fragment (scFv) of VCAM1 with 99mtechnetium (99mTc) and fluorescent markers to investigate its potential utility in detecting vulnerable plaques in animal models of atherosclerosis. METHODS: We labeled VCAM1 scFv with 99mTc and cyanine5 (CY5) and evaluated the probes on apolipoprotein E gene-deficient mice and New Zealand White rabbits with induced atherosclerosis. Histopathology and Western blot examinations confirmed atherosclerotic plaque and VCAM1 expression in the aortas. In vivo biodistribution of 99mTc-scFv-VCAM1 was studied. Abdominal organs of mice were removed after CY5-scFv-VCAM1 administration for aortic fluorescence imaging. Rabbits SPECT imaging of 99mTc-scFv-VCAM1 was performed and autoradiography (ARG) of the aortas was checked to confirm the tracer uptake. RESULTS: The radiochemical purity of 99mTc-scFv-VCAM1 was 98.72+/- 1.04% (n = 5) and its specific activity was 7.8 MBq/MUg. Biodistribution study indicated predominant probe clearance by kidneys. In fluorescence imaging, stronger signal from CY5-scFv-VCAM1 in the aorta was observed in atherosclerotic mice than that in controls. SPECT imaging with 99mTc-scFv-VCAM1 showed tracer uptake in the abdominal aorta and the aortic arch of atherosclerotic animals. ARG confirmed tracer uptake in the aortas of atherosclerotic rabbits, with higher uptake ratios of aortic arch/descending aorta in experimental animals (4.45 +/- 0.63, n = 5) than controls (1.12 +/- 0.15, n = 5; p < 0.05). CONCLUSIONS: SPECT and fluorescence imaging results showed the feasibility and effectiveness of detecting vulnerable plaque with scFv of VCAM1, indicating its potential for early diagnosis and evaluation of atherosclerosis. PMID- 27680309 TI - Ten-year outcome of early childhood traumatic brain injury: Diffusion tensor imaging of the ventral striatum in relation to executive functioning. AB - PRIMARY OBJECTIVE: The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity. RESEARCH DESIGN: Between a paediatric group with TBI and a group of typically developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity. METHODS AND PROCEDURES: Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests. MAIN OUTCOMES AND RESULTS: The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching). CONCLUSIONS: TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits. PMID- 27680311 TI - G-CSF improves CUMS-induced depressive behaviors through downregulating Ras/ERK/MAPK signaling pathway. AB - Neuronal plasticity in hippocampal neurons is closely related to memory, mood and behavior as well as in the development of depression. Granulocyte colony stimulating factor (G-CSF) can promote neuronal plasticity and enhance motor skills. However, the function of G-CSF in depression remains poorly understood. In this study, we explored the biological role and potential molecular mechanism of G-CSF on depression-like behaviors. Our results showed that G-CSF was significantly downregulated in the hippocampus of chronic unexpected mild stress (CUMS) rats. Administration of G-CSF significantly reversed CUMS-induced depression-like behaviors in the open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Moreover, G-CSF upregulated the expression of synaptic-associated proteins including polysialylated form of neural cell adhesion molecule (PSA-NCAM), synaptophysin (SYN), and postsynaptic density protein 95 (PSD-95) in the hippocampus and G-CSF significantly increased cell viability rate of hippocampal neurons in vitro. Further studies indicated that the renin-angiotensin system (Ras)/extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) signaling pathways was involved in the regulation of G-CSF on depressive-like behaviors and neuronal plasticity in CUMS rats. Taken together, our results showed that G-CSF improves depression like behaviors via inhibiting Ras/ERK/MAPK signaling pathways. Our study suggests that G-CSF may be a promising therapeutic strategy for the treatment of depression. PMID- 27680310 TI - Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver disease. AB - The liver X receptor (LXR) functions as a receptor for oxysterols and plays a critical role in the regulation of glucose and lipid metabolism. We recently described a synthetic LXR inverse agonist that displayed efficacy in treatment of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). This compound, SR9238, was designed to display liver specificity so as to avoid potential detrimental effects on reverse cholesterol transport in peripheral tissues. Here, we examined the effects of a LXR antagonist/inverse agonist, GSK2033, which displays systemic exposure. Although GSK2033 performed as expected in cell-based models as a LXR inverse agonist, it displayed unexpected activity in the mouse NAFLD model. The expression of lipogenic enzyme genes such as fatty acid synthase and sterol regulatory binding protein 1c were induced rather than suppressed and no effect on hepatic steatosis was found. Further characterization of the specificity of GSK2033 revealed that it displayed a significant degree of promiscuity, targeting a number of other nuclear receptors that could clearly alter hepatic gene expression. PMID- 27680312 TI - TBP-like protein (TLP) represses myogenesis via inhibition of the myogenin promoter. AB - TBP-like protein (TLP) is one of the metazoan-restricted transcription factors participating in development and differentiation, though the molecular mechanism by which TLP regulates these processes remains unclear. In this study, we investigated the relationship between TLP and myogenesis of mouse C2C12 myoblasts. We found that TLP gene expression decreases during myogenic differentiation. Overexpression and knockdown of TLP revealed that the levels of muscle-specific myosin heavy chain and the myogenic transcription factor myogenin are downregulated by TLP. TLP inhibits the progression of morphological change from myoblasts to myotubes, thereby suppressing myogenesis. We further show that TLP represses the promoter activity of myogenin. The proximal AT-rich sequence of the myogenin promoter is responsible for TLP-mediated transcriptional repression. The results of this study suggest that TLP inhibits myogenesis through downregulation of the myogenin gene. PMID- 27680313 TI - Novel roles of FKBP5 in muscle alteration induced by gravity change in mice. AB - Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions. FKBP5 was extracted as a gene whose expression was enhanced by hypergravity through the vestibular system. Stable FKBP5 overexpression increased the phosphorylations of Akt and p70 S6 kinase (muscle protein synthesis pathway) and myosin heavy chain, a myotube gene, mRNA level in mouse myoblastic C2C12 cells, although it reduced the mRNA levels of atrogin-1 and MuRF1, muscle protein degradation-related genes. In conclusion, we first showed that FKBP5 is induced by hypergravity through the vestibular system in anti-gravity muscle of mice. Our data suggest that FKBP5 might increase muscle mass through the enhancements of muscle protein synthesis and myotube differentiation as well as an inhibition of muscle protein degradation in mice. PMID- 27680314 TI - Light-induced Notch activity controls neurogenic and gliogenic potential of neural progenitors. AB - Oscillations in Notch signaling are essential for reserving neural progenitors for cellular diversity in developing brains. Thus, steady and prolonged overactivation of Notch signaling is not suitable for generating neurons. To acquire greater temporal control of Notch activity and mimic endogenous oscillating signals, here we adopted a light-inducible transgene system to induce active form of Notch NICD in neural progenitors. Alternating Notch activity saved more progenitors that are prone to produce neurons creating larger number of mixed clones with neurons and progenitors in vitro, compared to groups with no light or continuous light stimulus. Furthermore, more upper layer neurons and astrocytes arose upon intermittent Notch activity, indicating that dynamic Notch activity maintains neural progeny and fine-tune neuron-glia diversity. PMID- 27680315 TI - Cited2 participates in cardiomyocyte apoptosis and maternal diabetes-induced congenital heart abnormality. AB - Gestational diabetes mellitus is a risk factor for abnormal heart development, but the molecular basis remains obscure. To further analyze this, the hyperglycemia rat and cell model were established in this study. The results showed that hyperglycemic rats gained significantly less weight during gestation than controls. The number of embryos per litter was significantly reduced in diabetic mothers compared to controls. Ventricular wall thickness was often decreased in the diabetic offspring and cardiomyocyte apoptosis participated in ventricular wall thinness. Our results also indicated that Cited2 expression decreased in the heart tissues of diabetic-exposed embryos comparing with the control. The vitro results showed that down-regulation of Cited2 was associated with high glucose-induced apoptosis in cardiomyocytes in vitro. Over-expression of Cited2 gene restrained the cardiomyocyte apoptosis induced by high glucose. Furthermore, Cited2 S192G mutation partly inhibited the capacity of Cited2 to suppress apoptosis induced by high glucose in cardiomyocytes. This showed the critical role of Cited2 in high glucose-induced cardiomyocytes apoptosis. Data from this study found the association of Cited2 down regulation with cardiomyocytes apoptosis and maternal diabetes-induced ventricular wall thinness genesis. PMID- 27680316 TI - Implicit Racial Bias in Medical School Admissions. AB - PROBLEM: Implicit white race preference has been associated with discrimination in the education, criminal justice, and health care systems and could impede the entry of African Americans into the medical profession, where they and other minorities remain underrepresented. Little is known about implicit racial bias in medical school admissions committees. APPROACH: To measure implicit racial bias, all 140 members of the Ohio State University College of Medicine (OSUCOM) admissions committee took the black-white implicit association test (IAT) prior to the 2012-2013 cycle. Results were collated by gender and student versus faculty status. To record their impressions of the impact of the IAT on the admissions process, members took a survey at the end of the cycle, which 100 (71%) completed. OUTCOMES: All groups (men, women, students, faculty) displayed significant levels of implicit white preference; men (d = 0.697) and faculty (d = 0.820) had the largest bias measures (P < .001). Most survey respondents (67%) thought the IAT might be helpful in reducing bias, 48% were conscious of their individual results when interviewing candidates in the next cycle, and 21% reported knowledge of their IAT results impacted their admissions decisions in the subsequent cycle. The class that matriculated following the IAT exercise was the most diverse in OSUCOM's history at that time. NEXT STEPS: Future directions include preceding and following the IAT with more robust reflection and education on unconscious bias. The authors join others in calling for an examination of bias at all levels of academic medicine. PMID- 27680317 TI - Flipping the Quality Improvement Classroom in Residency Education. AB - PURPOSE: The flipped classroom (FC), in which instructional content is delivered before class with class time devoted to knowledge application, has the potential to engage residents. A Mayo Clinic Internal Medicine Residency Program study was conducted to validate an FC perception instrument (FCPI); determine whether participation improved FC perceptions; and determine associations between resident characteristics, change in quality improvement (QI) knowledge, and FC perception scores. METHOD: All 143 internal medicine residents at Mayo Clinic, Rochester participated from 2014 to 2015; some experienced a flipped QI curriculum and others completed the traditional nonflipped course. The FCPI was developed, and factor analysis revealed an intuitive two-factor structure: preclass activity and in-class application. Residents were surveyed before and after the monthlong curriculum to measure changes in perception, and the QI Knowledge Assessment Tool was employed to measure knowledge improvement. RESULTS: Postcourse FCPI scores significantly increased for three of the eight items. QI knowledge increased significantly among residents who experienced the FC compared with residents who completed the non-FC curriculum. Those without prior FC exposure demonstrated a significant increase in QI knowledge compared with those with previous FC experience. The FCPI had compelling validity evidence with improved scores after curriculum exposure and associations with greater engagement in online modules. CONCLUSIONS: Residents who participated in the FC demonstrated improved QI knowledge compared with the control group. Residents valued the in-class application sessions more than the online component. These findings have important implications for graduate medical education as residency training programs increasingly use FC models. PMID- 27680318 TI - Integrating Theory, Content, and Method to Foster Critical Consciousness in Medical Students: A Comprehensive Model for Cultural Competence Training. AB - Many efforts to design introductory "cultural competence" courses for medical students rely on an information delivery (competence) paradigm, which can exoticize patients while obscuring social context, medical culture, and power structures. Other approaches foster a general open-minded orientation, which can remain nebulous without clear grounding principles. Medical educators are increasingly recognizing the limitations of both approaches and calling for strategies that reenvision cultural competence training. Successfully realizing such alternative strategies requires the development of comprehensive models that specify and integrate theoretical frameworks, content, and teaching principles.In this article, the authors present one such model: Introduction to Medicine and Society (IMS), a required cultural competence course launched in 2013 for first year medical students at the Perelman School of Medicine at the University of Pennsylvania. Building on critical pedagogy, IMS is centered on a novel specification of "critical consciousness" in clinical practice as an orientation to understanding and pragmatic action in three relational domains: internal, interpersonal, and structural. Instead of transmitting discrete "facts" about patient "types," IMS content provokes students to engage with complex questions bridging the three domains. Learning takes place in a small-group space specifically designed to spur transformation toward critical consciousness. After discussing the three key components of the course design and describing a representative session, the authors discuss the IMS model's implications, reception by students and faculty, and potential for expansion. Their early experience suggests the IMS model successfully engages students and prepares future physicians to critically examine experiences, manage interpersonal dynamics, and structurally contextualize patient encounters. PMID- 27680319 TI - Expanding Group Peer Review: A Proposal for Medical Education Scholarship. AB - After participating in a group peer-review exercise at a workshop presented by Academic Medicine and MedEdPORTAL editors at the 2015 Association of American Medical Colleges Medical Education Meeting, the authors realized that the way their work group reviewed a manuscript was very different from the way by which they each would have reviewed the paper as an individual. Further, the group peer review process yielded more robust feedback for the manuscript's authors than did the traditional individual peer-review process. This realization motivated the authors to reconvene and collaborate to write this Commentary to share their experience and propose the expanded use of group peer review in medical education scholarship.The authors consider the benefits of a peer-review process for reviewers, including learning how to improve their own manuscripts. They suggest that the benefits of a team review model may be similar to those of teamwork and team-based learning in medicine and medical education. They call for research to investigate this, to provide evidence to support group review, and to determine whether specific paper types would benefit most from team review (e.g., particularly complex manuscripts, those receiving widely disparate initial individual reviews). In addition, the authors propose ways in which a team-based approach to peer review could be expanded by journals and institutions. They believe that exploring the use of group peer review potentially could create a new methodology for skill development in research and scholarly writing and could enhance the quality of medical education scholarship. PMID- 27680320 TI - Design, Implementation, and Evaluation of a Simulation-Based Clinical Correlation Curriculum as an Adjunctive Pedagogy in an Anatomy Course. AB - PROBLEM: Because reported use of simulation in preclinical basic science courses is limited, the authors describe the design, implementation, and preliminary evaluation of a simulation-based clinical correlation curriculum in an anatomy course for first-year medical students at Perdana University Graduate School of Medicine (in collaboration with Johns Hopkins University School of Medicine). APPROACH: The simulation curriculum, with five weekly modules, was a component of a noncadaveric human anatomy course for three classes (n = 81 students) from September 2011 to November 2013. The modules were designed around major anatomical regions (thorax; abdomen and pelvis; lower extremities and back; upper extremities; and head and neck) and used various types of simulation (standardized patients, high-fidelity simulators, and task trainers). Several methods were used to evaluate the curriculum's efficacy, including comparing pre- versus posttest scores and comparing posttest scores against the score on 15 clinical correlation final exam questions. OUTCOMES: A total of 81 students (response rate: 100%) completed all pre- and posttests and consented to participate. Posttest scores suggest significant knowledge acquisition and better consistency of performance after participation in the curriculum. The comparison of performance on the posttests and final exam suggests that using simulation as an adjunctive pedagogy can lead to excellent short-term knowledge retention. NEXT STEPS: Simulation-based medical education may prove useful in preclinical basic science curricula. Next steps should be to validate the use of this approach, demonstrate cost-efficacy or the "return on investment" for educational and institutional leadership, and examine longer-term knowledge retention. PMID- 27680321 TI - Congratulations! Your Article Has Been Accepted. Now What? Media, Social Media, and Other Outlets for Promoting Your Work. PMID- 27680322 TI - Twitter as a Potential Data Source for Cardiovascular Disease Research. AB - Importance: As society is increasingly becoming more networked, researchers are beginning to explore how social media can be used to study person-to-person communication about health and health care use. Twitter is an online messaging platform used by more than 300 million people who have generated several billion Tweets, yet little work has focused on the potential applications of these data for studying public attitudes and behaviors associated with cardiovascular health. Objective: To describe the volume and content of Tweets associated with cardiovascular disease as well as the characteristics of Twitter users. Design, Setting, and Participants: We used Twitter to access a random sample of approximately 10 billion English-language Tweets originating from US counties from July 23, 2009, to February 5, 2015, associated with cardiovascular disease. We characterized each Tweet relative to estimated user demographics. A random subset of 2500 Tweets was hand-coded for content and modifiers. Main Outcomes and Measures: The volume of Tweets about cardiovascular disease and the content of these Tweets. Results: Of 550 338 Tweets associated with cardiovascular disease, the terms diabetes (n = 239 989) and myocardial infarction (n = 269 907) were used more frequently than heart failure (n = 9414). Users who Tweeted about cardiovascular disease were more likely to be older than the general population of Twitter users (mean age, 28.7 vs 25.4 years; P < .01) and less likely to be male (59 082 of 124 896 [47.3%] vs 8433 of 17 270 [48.8%]; P < .01). Most Tweets (2338 of 2500 [93.5%]) were associated with a health topic; common themes of Tweets included risk factors (1048 of 2500 [41.9%]), awareness (585 of 2500 [23.4%]), and management (541 of 2500 [21.6%]) of cardiovascular disease. Conclusions and Relevance: Twitter offers promise for studying public communication about cardiovascular disease. PMID- 27680324 TI - Association of Hormonal Contraception With Depression. AB - Importance: Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. Objective: To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. Design, Setting, and Participants: This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016. Exposures: Use of different types of hormonal contraception. Main Outcomes and Measures: With time varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital. Results: A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75 1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Conclusions and Relevance: Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use. PMID- 27680323 TI - Exposure to metal oxide nanoparticles administered at occupationally relevant doses induces pulmonary effects in mice. AB - In spite of the great promises that the development of nanotechnologies can offer, concerns regarding potential adverse health effects of occupational exposure to nanoparticle (NP) is raised. We recently identified metal oxide NP in lung tissue sections of welders, located inside macrophages infiltrated in fibrous regions. This suggests a role of these NP in the lung alterations observed in welders. We therefore designed a study aimed to investigate the pulmonary effects, in mice, of repeated exposure to NP administered at occupationally relevant doses. We therefore chose four metal oxide NPs representative of those found in the welder's lungs: Fe2O3, Fe3O4, MnFe2O4 and CrOOH. These NPs were administered weekly for up to 3 months at two different doses: 5 MUg, chosen as occupationally relevant to welding activity, and 50 MUg, chosen as occupationally relevant to the context of an NP-manufacturing facility. Our results show that 3 month-repeated exposures to 5 MUg NP induced limited pulmonary effects, characterized by the development of a mild peribronchiolar fibrosis observed for MnFe2O4 and CrOOH NP only. This fibrotic event was further extended in terms of intensity and localization after the repeated administration of 50 MUg NP: all but Fe2O3 NP induced the development of peribronchiolar, perivascular and alveolar fibrosis, together with an interstitial inflammation. Our data demonstrate for the first time a potential risk for respiratory health posed by repeated exposure to NP at occupationally relevant doses. Given these results, the development of occupational exposure limits (OELs) specifically dedicated to NP exposure might therefore be an important issue to address. PMID- 27680326 TI - A comparative study on the regulatory region of the PERIOD1 gene among diurnal/nocturnal primates. AB - BACKGROUND: The circadian clock is set up around a 24-h period in humans who are awake in the daytime and sleep in the nighttime, accompanied with physiological and metabolic rhythms. Most haplorhine primates, including humans, are diurnal, while most "primitive" strepsirrhine primates are nocturnal, suggesting primates have evolved from nocturnal to diurnal habits. The mechanisms of physiological changes causing the habits and of genetic changes causing the physiological changes are, however, unknown. To reveal these mechanisms, we focus on the nucleotide sequences of the regulatory region of the PERIOD1 (PER1) gene that is known as one of the key elements of the circadian clock in mammalians. METHODS: We determined nucleotide sequences of the regulatory region of PER1 concerning the gene expression for six primates and compared those with those of eight primates from the international DNA database. Based on the sequence data, we constructed a phylogenetic tree including both the diurnal/nocturnal species and investigated the guanine and cytosine (GC) content in the regulatory region. RESULTS: The motif sequences regulating gene expression were evolutionary conservative in the primates examined. The phylogenetic tree simply showed phylogenetic relationship among the species and no branching pattern distinguishable between the diurnal and nocturnal groups. We found two cores showing a statistically significant difference between the diurnal and the nocturnal habits related to the GC contents of the regulatory region of PER1. CONCLUSION: Our results suggest the possibility that the two cores in the upstream region of PER1 are related to the regulation of gene expression leading to behavioral differences between diurnal and nocturnal primates. PMID- 27680327 TI - Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study. AB - BACKGROUND: To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment - diet-only versus additional insulin therapy - were based on the 2010 national Dutch guidelines. METHODS: Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens -diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population. RESULTS: A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing >=4500 g, Apgar score <7 at 5 min, respiratory support, preterm delivery, and admission to the neonatology department. Neonates born in the insulin-group had a lower birth weight compared with the diet-group (3364 vs. 3467 g, p = 0.005) and a lower gestational age at birth (p = 0.001). However, birth weight was not different between the groups when expressed in percentiles, adjusted for gestational age, gender, parity, and ethnicity. The occurrence of preeclampsia and gestational hypertension was comparable between the groups. In the insulin-group, labour was more often induced and more planned caesarean sections were performed (p = 0.001). Compared with the general obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p = <0.001). CONCLUSIONS: Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort. PMID- 27680325 TI - Effects of supervised aerobic and strength training in overweight and grade I obese pregnant women on maternal and foetal health markers: the GESTAFIT randomized controlled trial. AB - BACKGROUND: During pregnancy, a sedentary lifestyle may have negative consequences on maternal and foetal health status. The main objective of this project is to assess the effects of an exercise intervention in overweight and grade I obese pregnant on maternal and foetal health markers. METHODS/DESIGN: The present study aims to recruit 60 overweight and grade I obese women interested in participating in an exercise intervention program from the 17th gestational week until delivery. Women will be randomized to either an exercise (three 60-min sessions/week of combined aerobic and strength training and pelvic floor exercises), or usual care (control) group (30 women per group). The primary outcome measures are maternal weight gain, and maternal and neonatal glycaemic profile. Secondary outcome measures are: i) perinatal obstetric records; i) body composition; iii) dietary patterns; iv) physical fitness; v) low-back pain; vi) objectively measured physical activity and sedentary behaviour; vii) haematology and biochemical analyses; viii) oxidative stress; ix) pro- and anti-inflammatory markers; x) bone health biomarkers; xi) sleep quality; xii) mental health, quality of life and positive health. DISCUSSION: The findings of this project will help to identify strategies for primary prevention and health promotion based on this exercise-based intervention program among overweight and grade I obese pregnant women. TRIAL REGISTRATION: NCT02582567 ; Date of registration: 20/10/2015. PMID- 27680329 TI - Current Trends and Healthcare Resource Usage in the Hospital Treatment of Primary Malignant Brain Tumor in Japan: A National Survey Using the Diagnostic Procedure Combination Database (J-ASPECT Study-Brain Tumor). AB - We conducted this study to clarify the current trends and healthcare resource usage in the treatment of inpatients with primary malignant brain tumors. The Diagnostic Procedure Combination (DPC) data of all inpatients treated between 2013 and 2014 in the 370 core and branch hospitals enrolled in the Japanese Neurosurgical Society training program were collected. DPC is a discharge abstract and administrative claims database of inpatients. We assessed 6,142 primary, malignant brain tumor patients. Patient information, diagnostic information, treatment procedure, and healthcare resource usage were analyzed. Chemotherapy was the most frequent treatment (27% of cases), followed by surgery (13%) and surgery + chemo-radiotherapy (11%). Temozolomide (TMZ), the most frequently used chemotherapeutic drug, was administered to 1,236 patients. Concomitant TMZ and radiotherapy was administered to 816 patients, and was performed according to the Stupp regimen in many cases. The mean length of hospital stay (LOS) was 16 days, and the mean medical cost was 1,077,690 yen. The average medical cost of TMZ-only treatment was 1,138,620 yen whilst it was 4,424,300 yen in concomitant TMZ patients. The LOS was significantly shorter in high-volume than in low-volume hospitals, and the medical cost was higher in hospitals treating 21-50 patients compared to those treating 1-10 patients. However, the direct medical cost of TMZ treatment was the same across different volume hospitals. This is the first report of current trends and healthcare resource usage in the treatment of primary malignant brain tumor inpatients in the TMZ era in Japan. PMID- 27680330 TI - Status and Future Perspectives of Utilizing Big Data in Neurosurgical and Stroke Research. AB - The management, analysis, and integration of Big Data have received increasing attention in healthcare research as well as in medical bioinformatics. The J ASPECT study is the first nationwide survey in Japan on the real-world setting of stroke care using data obtained from the diagnosis procedure combination-based payment system. The J-ASPECT study demonstrated a significant association between comprehensive stroke care (CSC) capacity and the hospital volume of stroke interventions in Japan; further, it showed that CSC capabilities were associated with reduced in-hospital mortality rates. Our study aims to create new evidence and insight from 'real world' neurosurgical practice and stroke care in Japan using Big Data. The final aim of this study is to develop effective methods to bridge the evidence-practice gap in acute stroke healthcare. In this study, the authors describe the status and future perspectives of the development of a new method of stroke registry as a powerful tool for acute stroke care research. PMID- 27680331 TI - A Modified Technique with a New Device of Laparoscopic Percutaneous Extraperitoneal Closure for Pediatric Inguinal Hernia. AB - INTRODUCTION: Laparoscopic percutaneous extraperitoneal closure (LPEC) in boys is more complex than in girls, because the vas deferens and testicular vessels must be separated from the peritoneum. We therefore developed a needle-shaped surgical instrument that enables blunt separation. Here, we report the effectiveness of this new device. SURGICAL TECHNIQUE: The new device is a ligature carrier consisting of (1) an inner tube (19-G blunt needle) through which slides a rod with a loop wire at its tip that can catch and release suture materials and (2) an outer tube (17-G needle) with a cutting edge. The blunt-structured inner tube enables blunt separation. All actions (stabbing, separation, and catching) in the LPEC procedure that are required to close the hernia orifice using a thread are facilitated through a simple small incision by switching between the inner and outer tubes. SUBJECTS AND METHODS: From January 2013 to September 2015, 73 boys with inguinal hernia or hydrocele underwent LPEC, and the new device was used in 45 of these cases. We compared surgical results between cases wherein the new (group A) and conventional devices (LPEC needle; group B) were used. RESULTS: The mean surgery duration was 33.4 and 34.8 min for groups A and B, respectively. Neither group experienced complications during or after surgery. CONCLUSION: Our findings suggest that the newly developed needle device may improve the safety of the LPEC procedure for boys, although further investigation involving more cases and long-term follow-up is needed in the future. PMID- 27680333 TI - Do real nurses work in theatres? AB - Currently on the conference circuit propounding some radical theories, Keele University's Professor Roger Dyson is stirring up a hornets' nest over the pros - or in his view the cons - of Project 2000. PMID- 27680328 TI - Phage display as a promising approach for vaccine development. AB - Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms. PMID- 27680334 TI - ? AB - Rewarding excellence: Health Secretary Virginia Bottomley presented the Clinical Practice and Management Training Awards to Claire Breslin(pictured above) and 11 other finalists at a special luncheon in London this week. The Awards, a joint initiative between the Royal College of Nursing, Smith& Nephew Medical andNursing Standard include a week long tailor made management course at Sundridge Park in Kent for all the whining nurses. Further details in our special supplement on page 49. PMID- 27680335 TI - Project 2000: the wrong sort of preparation for the future of nursing? AB - Project 2000 is 'crippling' the profession and is completely the wrong sort of preparation for nurses of the future, according to controversial management figure, Professor Roger Dyson. PMID- 27680332 TI - Long non-coding RNAs in the regulation of myeloid cells. AB - Long non-coding RNAs (lncRNAs) have been attracting immense research interests. The relevance of lncRNAs in biological and physiological as well as in pathological processes has increased along with the understanding of their various regulatory mechanisms. Abundant studies have indicated that lncRNAs are involved in the differentiation, proliferation, activation, and initiation of apoptosis in different cell types. However, most studies about the regulating biology of lncRNAs are currently focused on cancer cells. This review is focused on the widely unexplored role of lncRNAs in the cell fate of myeloid cells. In this review, we summarize recent studies that have confirmed lncRNAs to be essential in the development of myeloid cells under normal and pathological conditions. PMID- 27680336 TI - Hospitals should be run by the private sector. AB - Hospitals should be built and run by the private sector to avoid having to deal with NHS unions, according to new proposals from the Social Market Foundation. PMID- 27680337 TI - NI unions warn cuts will cause misery. AB - Cuts in services proposed by the Eastern Health Board in Northern Ireland will cause misery to the Province's most vulnerable client groups, unions have warned. PMID- 27680338 TI - 350 new community posts called a 'drop in the ocean'. AB - Nursing unions have described the 350 new community nursing posts identified by the London Implementation Group as a 'drop in the ocean', and say LIG's clearing house for redeploying staff affected by the Tomlinson changes will discriminate against nurses on lower grades. PMID- 27680339 TI - ? AB - Bar tenders: Nurses and physios from The Priory' Hospital in Edgbaston provided medical cover for competitors during lastweek's World Gymnastics Championships in Birmingham. Pictured are nurses Elaine Cooknell (front row, left), Mike Moore (Front row, back) Philip Pitt (back row, centre) and Findlay Smith (back row, right) with Laura Timmins on the beam and British women's team mates Zeta Lusack, Jackie Brady and Anna-lisa Acklam. PMID- 27680341 TI - National survey for mental illness. AB - The first-ever government-backed nationwide survey of mental illness was launched last week. It is being conducted by the Office of Population Censuses and Surveys and will try to measure the extent of psychiatric illness among adults throughout England, Scotland and Wales. PMID- 27680342 TI - Merger means anxiety for tutors. AB - Nurse tutors could be 'thrown on the scrap heap' when two London colleges of nursing merge, the RCN has warned. PMID- 27680343 TI - ? AB - Tackling disease: Blackburn Rovers, and England footballer AlanShearer, helped kick-off the Cystic Fibrosis Trust's National Appeal Week, which runs until Sunday. Helping out are CF sufferers LiamCrombie (front) and Jason Mellor who underwent a heart and lung transplant to help him to overcome the life threatening disorder. PMID- 27680344 TI - Older people face poor levels of care. AB - Older people in residential and nursing homes face 'scandalous'levels of care unless greater measures are taken to meet their needs, the RCN's Director of Policy and Research has warned. PMID- 27680345 TI - Nurse wins L30,000 for religious discrimination. AB - A Catholic nurse won record damages for religious discrimination last week after claiming a health board unjustly failed to shortlist her for a job. PMID- 27680347 TI - Battle with GPs, says RCN. AB - Practice nurses fearing redundancy when the new health promotion banding system is introduced in July must fight to show GPs their worth. PMID- 27680346 TI - Unacceptable work conditions for PNs. AB - Most practice nurses are working in 'totally unacceptable' circumstances with minimal time allowed for study, and no employment contracts or job descriptions, a United Kingdom survey has revealed. PMID- 27680348 TI - ? AB - Participants at the National Practice Nurse Conference: (left to right) RCN Vice President Baroness Cox; Detective Chief Inspector Roger Michael, responsible for Family Support Units at Whitchurch, Treforest and Skewen: Clare Wilkinson, Senior Lecturer, Department of General Practice, University of Wales. PMID- 27680349 TI - Men need 'formal invitation' to take care of their health. AB - The best way to get men to take care of their health is with good recall procedures, believes senior lecturer in general practice, Tom O'Dowd. PMID- 27680351 TI - Failure to inform mothers on risk reduction revealed. AB - Midwives may be failing to tell women how to reduce the risk of spina bifida and other fetal diseases, it was suggested last week, after a survey showed many women are not aware of the benefits of folic acid. PMID- 27680352 TI - ? AB - Hands on help: A child at the new Craighalbert Centre for Children with Motor Impairments. The centre in Cumbernauld, Scotland, is the first purpose-built unit for children with cerebral palsy. PMID- 27680353 TI - Hit-and-run nurse is recovering. AB - A nurse who was run over by a hit-and-run driver who stole her car was recovering from serious injuries in an Oxford hospital last week. PMID- 27680354 TI - MMR vaccine programme suspended. AB - Practice nurses and health visitors face a three-week suspension of the MMR vaccination programme and will have to reassure parents who may be anxious about the delay, the RCN warned last week. PMID- 27680355 TI - Survey shows that asthma is stifling children's lifestyles. AB - Many children with asthma suffer regular symptoms that restrict their lifestyles, an important survey of paediatric asthma patients shows. More than 20,000 young people took part in the survey, which was carried out by a medical group, Action Asthma. PMID- 27680356 TI - Specialist nurses left feeling undervalued. AB - Specialist nurses who arrange social and recreational activities for elderly people say their skills and contribution are undervalued by health service managers. PMID- 27680358 TI - Lower age limit for cervical screening. AB - The age limit for cervical screening could be lowered to 50 for women who have a history of negative smear test results, a new study has shown. PMID- 27680357 TI - World news. AB - Canada Patients will be put at risk by staff redundancies at hospitals in Ontario, a recent nursing conference in Toronto was told. PMID- 27680359 TI - Revised thresholds for hypertension treatment. AB - Revised thresholds for the pharmcological treatment of hypertension have been issued by the British Hypertension Society. PMID- 27680361 TI - Pets able to detect epileptic seizures? AB - Pet dogs may be able to detect when their owner is about to have an epileptic seizure, a new study suggests. PMID- 27680360 TI - Warning over effects of maternal alcohol abuse. AB - The effects of maternal alcohol abuse persist for many years, researchers have warned after following up children whose mothers drank heavily during pregnancy. PMID- 27680363 TI - Cholesterol lower in chronic hepatitis B. AB - The observed inverse association between blood cholesterol concentration and liver disease may be explained by chronic hepatitis B infection. PMID- 27680362 TI - Treating RSV in the immunocompromised. AB - Tribavirin may be a useful treatment for respiratory syncytial virus (RSV) in people who are immunocompromised. PMID- 27680364 TI - Asthma inhalers give unreliable dose. AB - Some exacerbations of asthma result from patients continuing to use metered dose inhalers beyond the specified number of sprays, American doctors believe. PMID- 27680365 TI - Exercise and calcium for teens and twenties. AB - Women in their twenties can substantially reduce the risk of developing osteoporosis by following the advice usually given to teenagers. PMID- 27680366 TI - Enhancing quality of life in bowel disease. AB - Nurses could improve the quality of life of patients with inflammatory bowel disease by focusing on areas of life where the disease has the greatest impact. PMID- 27680367 TI - Footing the bill. AB - Five days' study leave over three years may not sound a lot to the dedicated practitioner whose instinct is to keep up with professional developments. But to acash-strapped government faced with the bill it must seem daunting. PMID- 27680368 TI - Can the future turn out bright in the end? this reader's tale shows the bitter legacy of redundancy can be beaten by a positive attitude. AB - Anne Greenaway's poignant Nurses work campaign article, Life after Redundancy (March3), reflected my experiences of the amalgamation of my college of nursing and the poor manner in which the resulting redundancies were handled. PMID- 27680369 TI - Is my diploma now rendered useless? AB - The media is filled with reports of student nurses' poor prospects, and there seem to,be more positions available for,unqualified staff willing to take the notorious NVQ. If that is not depressing enough I for a hardworking and enthusiastic person one month |into the branch programme, I now read chat my branch may cease to exist (P2000 mental handicap branch may 'go, News, April 7). PMID- 27680370 TI - Care is not free, nor are rights forfeit. AB - Joan Lynn's insightful article (Don't tell the patient, March24) examining the problems patients encounter with paternalistic healthcare professionals who fail to respect their autonomy, carried a statement that may explain why such professionals continue to behave in this way. PMID- 27680371 TI - Keep up the pressure, back the campaign. AB - It will come as no consolation to Lorraine Darbyshire to know that she is but one of many UK nursing students facing the likelihood of unemployment after registration (Letters, April 7). PMID- 27680372 TI - With thanks for a wonderful weekend. AB - I have just returned from a trip to Denmark that I won in Nursing Standard's September1992 competition. PMID- 27680374 TI - Sick, tired and losing patience with bullies. AB - I would like to add my story to your series of articles and letters on bullying at work. PMID- 27680373 TI - Contemplation could be cost-effective. AB - I agree with Barry Clifton that many nurses arc so busy meeting deadlines and working cost-effectively that they have little time for reflection (Ivory towers of strength, Viewpoint, March 17). PMID- 27680376 TI - Information exchange. AB - I am part of a group currently reviewing the material used to promote the school health service in Newcastle. PMID- 27680375 TI - Auxiliaries fail to seethe funny side. AB - As a community nursing auxiliary I was disappointed to see the cartoon (March 24) of a nurse saying to a patient. PMID- 27680377 TI - Ethics V Tschudin Scutari 150pp L12.99 1-871-364-79-5. AB - Ethics as a subject is sometimes thought of as a professional abstract that has no relevance to the real world and belongs in the rather 'stuffy' realm of academia. PMID- 27680380 TI - Gossip. AB - Worried about your future in nursing? Looking for something less stressful? Thinking about journalism? Forget it. PMID- 27680379 TI - Teaching Students in Clinical Settings J Stengelhofen J Campling Chapman & Hall 226pp L13.95 0-412-45250-2. AB - As purely background reading for the English National Board (ENB998) course, 'Teaching and Assessing', I found Teaching Students in Clinical Settings both enjoyable and informative. PMID- 27680381 TI - Judging the winners. AB - What a challenge. Nearly 300 readers were sufficiently inspired by the Clinical Practice and Management Award series to enter the competition. And because most people answered the questions correctly, the judges read all the essays. Selecting 12 award winners was daunting, but at the same time, the judges found it an encouraging experience. The entrants expressed their enthusiasm to learn, to collaborate with managers, to manage others more effectively, and to be committed to learning more about this important aspect of health care delivery. The series achieved its aim of joining clinical practitioners and managers in a collaborative working relationship. PMID- 27680382 TI - Clinical Practice And Management Essay Winners. AB - The following winners wrote essays on why they would like to attend a residential course to further their knowledge in clinical management. Here are some extracts from the winning essays. PMID- 27680383 TI - Career listings. PMID- 27680385 TI - Development of A Teen-Focused Exergame. AB - INTRODUCTION: Exergames require body movement to play and may be an effective method for enhancing teen physical activity (PA). However, results have been mixed. Innovative methods are needed to develop Exergames that increase and maintain PA. Self-representational avatars, or avatars created from a digital image of an individual, may increase PA (e.g., intensity, duration) during Exergame play. This article addresses this novel idea by describing the development of an Exergame played with a self-representational avatar. MATERIALS AND METHODS: Twelve- to 14-year-olds, stratified by gender, body mass index, and PA, were invited to participate in two rounds of data collection. Each round consisted of an online survey, followed by a telephone interview to ensure comprehension of survey responses. After the first round, an Exergame prototype and the system for creating the self-representational avatar were created. A second round of data was collected to obtain information with which to create a fully functional Exergame and the avatar creation system. RESULTS: Forty-eight teens were recruited. The sample was multi-ethnic (41.7% White, 37.5% Black, 18.8% Hispanic, 2.1% Mixed/Other). Complete data were obtained on 48 teens in the first round of data collection and on 43 teens in the second round. Teens provided important information regarding preferences and expectations. Gender similarities and differences were observed. CONCLUSION: This research contributes to the body of knowledge regarding how to design an appealing Exergame for teens navigated by a self-representational avatar. PMID- 27680384 TI - Differentiated THP-1 Cells Exposed to Pathogenic and Nonpathogenic Borrelia Species Demonstrate Minimal Differences in Production of Four Inflammatory Cytokines. AB - : Tick-borne borreliae include Lyme disease and relapsing fever agents, and they are transmitted primarily by ixodid (hard) and argasid (soft) tick vectors, respectively. Tick-host interactions during feeding are complex, with host immune responses influenced by biological differences in tick feeding and individual differences within and between host species. One of the first encounters for spirochetes entering vertebrate host skin is with local antigen-presenting cells, regardless of whether the tick-associated Borrelia sp. is pathogenic. In this study, we performed a basic comparison of cytokine responses in THP-1-derived macrophages after exposure to selected borreliae, including a nonpathogen. By using THP-1 cells, differentiated to macrophages, we eliminated variations in host response and reduced the system to an in vitro model to evaluate the extent to which the Borrelia spp. influence cytokine production. Differentiated THP-1 cells were exposed to four Borrelia spp., Borrelia hermsii (DAH), Borrelia burgdorferi (B31), B. burgdorferi (NC-2), or Borrelia lonestari (LS-1), or lipopolysaccharides (LPS) (activated) or media (no treatment) controls. Intracellular and secreted interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured using flow cytometric and Luminex-based assays, respectively, at 6, 24, and 48 h postexposure time points. Using a general linear model ANOVA for each cytokine, treatment (all Borrelia spp. and LPS compared to no treatment) had a significant effect on secreted TNF alpha only. Time point had a significant effect on intracellular IFN-gamma, TNF alpha and IL-6. However, we did not see significant differences in selected cytokines among Borrelia spp. TREATMENTS: Thus, in this model, we were unable to distinguish pathogenic from nonpathogenic borreliae using the limited array of selected cytokines. While unique immune profiles may be detectable in an in vitro model and may reveal predictors for pathogenicity in borreliae of unknown pathogenicity, a larger panel of cytokines would be desirable to test. PMID- 27680386 TI - Spatially inhomogeneous electron state deep in the extreme quantum limit of strontium titanate. AB - When an electronic system is subjected to a sufficiently strong magnetic field that the cyclotron energy is much larger than the Fermi energy, the system enters the extreme quantum limit (EQL) and becomes susceptible to a number of instabilities. Bringing a three-dimensional electronic system deeply into the EQL can be difficult however, since it requires a small Fermi energy, large magnetic field, and low disorder. Here we present an experimental study of the EQL in lightly-doped single crystals of strontium titanate. Our experiments probe deeply into the regime where theory has long predicted an interaction-driven charge density wave or Wigner crystal state. A number of interesting features arise in the transport in this regime, including a striking re-entrant nonlinearity in the current-voltage characteristics. We discuss these features in the context of possible correlated electron states, and present an alternative picture based on magnetic-field induced puddling of electrons. PMID- 27680387 TI - Interplay between cell cycle and autophagy induced by boswellic acid analog. AB - In this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 MUM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death. PMID- 27680388 TI - Unsupervised Data Mining in nanoscale X-ray Spectro-Microscopic Study of NdFeB Magnet. AB - Novel developments in X-ray based spectro-microscopic characterization techniques have increased the rate of acquisition of spatially resolved spectroscopic data by several orders of magnitude over what was possible a few years ago. This accelerated data acquisition, with high spatial resolution at nanoscale and sensitivity to subtle differences in chemistry and atomic structure, provides a unique opportunity to investigate hierarchically complex and structurally heterogeneous systems found in functional devices and materials systems. However, handling and analyzing the large volume data generated poses significant challenges. Here we apply an unsupervised data-mining algorithm known as DBSCAN to study a rare-earth element based permanent magnet material, Nd2Fe14B. We are able to reduce a large spectro-microscopic dataset of over 300,000 spectra to 3, preserving much of the underlying information. Scientists can easily and quickly analyze in detail three characteristic spectra. Our approach can rapidly provide a concise representation of a large and complex dataset to materials scientists and chemists. For example, it shows that the surface of common Nd2Fe14B magnet is chemically and structurally very different from the bulk, suggesting a possible surface alteration effect possibly due to the corrosion, which could affect the material's overall properties. PMID- 27680389 TI - Repetitive Thinking in Alcohol-Dependent Patients. AB - BACKGROUND: Recent studies proposed that a tendency to have repetitive negative thinking (RNT) could be a predictor of alcohol use. Nevertheless, results differ depending on the studied population (nonclinical samples or patients with alcohol abuse or alcohol dependence) and on the type of repetitive thinking (rumination or worry). These heterogeneous results might be explained by the impact of anxiety and depression level on RNT and alcohol consumption. OBJECTIVES: The aim of the present study was to explore different type of repetitive thinking (i.e., worry, brooding and reflection rumination, analytic-abstract repetitive thinking, and concrete-experiential thinking) in a clinical sample of alcohol-dependent patients and a non-clinical sample and the role played by depression and anxiety. METHOD: Eighty-four inpatients with a diagnosis of alcohol dependence and 68 individuals from a nonclinical sample completed questionnaires evaluating repetitive thinking, anxiety, depression and alcohol consumption. RESULTS: Mann Whitney U tests showed that patients with alcohol dependence reported more analytic-abstract repetitive thinking, brooding and reflection rumination and worry, as well as anxious and depressive symptoms, compared with social drinkers, who reported more concrete-experiential repetitive thinking. Moreover, a multiple mediation model indicated that the link between RNT and alcohol consumption was significantly mediated by both anxiety and depression. Conclusion/Importance: The results support the implication of RNT in alcohol dependence and the distinction between different types of repetitive thinking with adaptive or maladaptive consequences. This link seems to be explained by the levels of depression and anxiety that mediate the impact of RNT on alcohol consumption. PMID- 27680391 TI - Phylogeny and biogeography of the remarkable genus Bondarzewia (Basidiomycota, Russulales). AB - Bondarzewia is a conspicuous and widely distributed mushroom genus, but little is known about its origin and biogeography. Here, we investigated the systematics and biogeography of Bondarzewia species using multi-locus phylogenetic analysis. Four genetic markers, including the internal transcribed spacer (ITS), large nuclear ribosomal RNA subunit (nLSU), elongation factor 1-alpha (tef1) and mitochondrial small subunit rDNA (mtSSU), were used to infer the phylogenetic relationships of Bondarzewia. We performed Bayesian evolutionary analysis on the gene datasets of the largest and second largest subunits of RNA polymerase II (RPB1 and RPB2). From the results, we inferred that the maximum crown age of Bondarzewia is approximately 25.5 million-years-ago (Mya) and that tropical East Asia is likely to be its ancestral area, with three possible expansions leading to its distribution in North America, Europe and Oceania. PMID- 27680390 TI - A randomized controlled trial to assess the central hemodynamic response to exercise in patients with transient ischaemic attack and minor stroke. AB - Early exercise engagement elicits meaningful changes in peripheral blood pressure in patients diagnosed with transient ischaemic attack (TIA) or minor stroke. However, central hemodynamic markers may provide clinicians with important diagnostic and prognostic information beyond that provided by peripheral blood pressure readings. The purpose of this single-centre, randomized, parallel-group clinical trial was to determine the effect of a 12-week aerobic exercise intervention on central and peripheral hemodynamic variables in patients with TIA or minor stroke. In this study, 47 participants (66+/-10 years) completed a baseline assessment, which involved the measurement of central and peripheral hemodynamic parameters, undertaken in the morning, in a fasted state. Participants were randomized to either a 12-week exercise or control group on completion of the baseline assessment. An identical follow-up assessment was completed post intervention. Central hemodynamic variables were assessed using an oscillometric device at both assessments. Analysis of covariance demonstrated a significant interaction for central and peripheral blood pressure and augmentation index (all P<0.05; etap2.09-.11), with the exercise group presenting lower values than the control group post intervention (118+/-17 vs 132+/-28 mm Hg for central blood pressure; 125+/-19 vs 138+/-28 mm Hg for peripheral blood pressure; 104+/-49 vs 115+/-67% for augmentation index). The present study demonstrates that participation in an exercise program soon after stroke/TIA diagnosis may elicit significant beneficial changes to a patient's central systolic blood pressure and augmentation index. This may positively impact upon the treatment strategies implemented by clinicians in the care of patients with TIA and minor stroke. PMID- 27680392 TI - A role for Peroxisome Proliferator-Activated Receptor Beta in T cell development. AB - Metabolism plays an important role in T cell biology and changes in metabolism drive T cell differentiation and fate. Most research on the role of metabolism in T lymphocytes focuses on mature T cells while only few studies have investigated the role of metabolism in T cell development. In this study, we report that activation or overexpression of the transcription factor Peroxisome Proliferator Activated Receptor beta (PPARbeta) increases fatty acid oxidation in T cells. Furthermore, using both in vivo and in vitro models, we demonstrate that PPARbeta activation/overexpression inhibits thymic T cell development by decreasing proliferation of CD4-CD8- double-negative stage 4 (DN4) thymocytes. These results support a model where PPARbeta activation/overexpression favours fatty acid- instead of glucose-oxidation in developing T cells, thereby hampering the proliferative burst normally occurring at the DN4 stage of T cell development. As a consequence, the alphabeta T cells that are derived from DN4 thymocytes are dramatically decreased in peripheral lymphoid tissues, while the gammadelta T cell population remains untouched. This is the first report of a direct role for a member of the PPAR family of nuclear receptors in the development of T cells. PMID- 27680393 TI - [Causes, diagnosis and differential diagnosis of hyponatremia]. AB - Hyponatremia is a common electrolyte disorder that arises from disturbances in water metabolism. In cases of acute advanced hyponatremia, serious symptoms are predominant, while chronic mild hyponatremia causes minor symptoms such as slowness, depression or unsteadiness of gait. Any therapy of hyponatremia depends on the severity of its symptoms and on its specific etiology and diagnosis. Concerning the differential diagnosis of the type of hyponatremia, it is initially helpful to distinguish between euvolemic, hypervolemic and hypovolemic forms of hyponatremia. In order to distinguish between these 3 types of hyponatremia, it is best to assess the spontaneous urinary sodium concentration and to consider evidence from the medical history and the physical examination. Once the type of hyponatremia has been diagnosed, the next step is to decide which of the known etiologies of hyponatremia applies. Diagnostic problems may arise in mixed hyponatremia, a condition in which different types and etiologies of hyponatremia occur at the same time. In such cases it may be best to determine what appears to be the leading diagnosis. Another kind of diagnostic difficulty often occurs in simultaneous diuretic use. It may help to distinguish to which extracellular volume the types of hyponatremia relate on the basis of the fractional excretion of uric acid rather than on the urinary sodium concentration. PMID- 27680394 TI - [Chronic heart failure - new insights]. AB - Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to high morbidity and mortality a standardized and evidence-based therapy is crucial. This review presents new pharmacological and interventional developments, as well as new insights due to common comorbidities of patients with chronic heart failure like anemia and hyperkalemia. PMID- 27680395 TI - New York Polyclinic Medical School and Hospital. PMID- 27680396 TI - Methane Sources and Migration Mechanisms in Shallow Groundwaters in Parker and Hood Counties, Texas-A Heavy Noble Gas Analysis. AB - This study places constraints on the source and transport mechanisms of methane found in groundwater within the Barnett Shale footprint in Texas using dissolved noble gases, with particular emphasis on 84Kr and 132Xe. Dissolved methane concentrations are positively correlated with crustal 4He, 21Ne, and 40Ar and suggest that noble gases and methane originate from common sedimentary strata, likely the Strawn Group. In contrast to most samples, four water wells with the highest dissolved methane concentrations unequivocally show strong depletion of all atmospheric noble gases (20Ne, 36Ar, 84Kr, 132Xe) with respect to air saturated water (ASW). This is consistent with predicted noble gas concentrations in a water phase in contact with a gas phase with initial ASW composition at 18 degrees C-25 degrees C and it suggests an in situ, highly localized gas source. All of these four water wells tap into the Strawn Group and it is likely that small gas accumulations known to be present in the shallow subsurface were reached. Additionally, lack of correlation of 84Kr/36Ar and 132Xe/36Ar fractionation levels along with 4He/20Ne with distance to the nearest gas production wells does not support the notion that methane present in these groundwaters migrated from nearby production wells either conventional or using hydraulic fracturing techniques. PMID- 27680397 TI - Validation of international stroke scales for use by nurses in Greek settings. AB - BACKGROUND: Improving stroke outcomes by educating nurses in state-of-the-art stroke nursing skills is essential, but unfortunately, to date, there are limited validated stroke assessment scales for routine clinical and research use in Greece. OBJECTIVE: The aim of this paper is to validate and culturally adapt three internationally recognised stroke scales for use in Greece. METHODS: A critical appraisal of the international literature was undertaken to identify suitable scales to assess stroke impact: neurological, functional status and level of dependence. We identified: Scandinavian Stroke Scale (SSS), Barthel Index (BI) and modified Rankin Scale (mRS). They were formally translated and culturally adapted from English to Greek. Their validity was tested using Cronbach's alpha and Median Discrimination Index, while construct validity was checked by Principal Component Analysis (PCA). These were used on 57 consecutively selected patients with stroke from a Greek hospital, mean age 67.7 (+/-6.7 SD) years, range 54-85 years, length of stay, 8.5 (+/-2.7 SD) days. RESULTS: All three scales show high internal consistency. The Cronbach's alpha on admission/ discharge for the SSS ranged from 0.86 to 0.88. The BI's reliability ranged from 0.95 to 0.93. The Median Discrimination Index was 0.70 (SSS) and 0.83 (BI). PCA showed that although a significant general factor (F1) explains most of the variance (57.0% on admission and 56.4% on discharge) a second factor (F2) of less significance was also highlighted. The convergent validity of the three scales was confirmed. DISCUSSION: The stroke tools selected showed high reliability and validity, thus making these suitable for use in Greek clinical/academic environments. All three scales used are almost routinely undertaken in stroke studies internationally and form a backdrop for bio statistical, functional and social outcome post-stroke. CONCLUSIONS: The Greek version of the stroke tools show that both SSS and BI have high internal consistency and reliability and together with the mRS could be used in any Greek stroke care delivery setting. PMID- 27680398 TI - Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor alpha (ERalpha) Polymorphism in Postmenopausal Women. AB - BACKGROUND The goal of this study was to investigate the relationship between cognitive functions and the level of endogenous estradiol in postmenopausal women, according to which estrogen receptor alpha (ERalpha) polymorphism the woman carries. MATERIAL AND METHODS The study group consisted of 210 women. The inclusion criteria were: minimum 2 years after the last menstruation, FSH concentration 30 U/ml, and no dementia signs on Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. Genotyping of the ERa polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR RFLP). Blood plasma was tested for FSH and estradiol (E2). Statistical analysis was performed using STATISTICA software. RESULTS A relationship was confirmed between standard scores for 3 cognitive functions: general memory, verbal memory, and processing speed, and the XbaI polymorphism in the women in the study. In the group of women with genotype TT PvuII, significant positive relationships were observed between the concentration of E2 and the standard scores of 3 cognitive functions: general memory, verbal memory, and processing speed. In the group of women with genotype TC PvuII, significant negative correlations were found between the concentration of E2 and the standard scores of 4 cognitive functions: NCI, general memory, verbal memory, and processing speed. CONCLUSIONS ERalpha polymorphism exerted an effect on the interaction between the concentration of estradiol and the results for cognitive functions. The concentration of estradiol did not depend on Xba1 and PvuII polymorphisms. The results for cognitive functions depended on which Xba1 polymorphism the woman carried. PMID- 27680400 TI - Use of the Hydantoin Directing Group in Ruthenium(II)-Catalyzed C-H Functionalization. AB - Ruthenium(II)-catalyzed C-H functionalization of N-arylhydantoins is herein described. The biologically relevant hydantoin (imidazolidinedione) heterocycle functions as a weakly coordinating directing group in a C-H alkenylation reaction. The reaction gave a wide scope of 23 examples with yields up to 94% in the green solvent 2-MeTHF. Functionalization of API nilutamide (antiandrogen) is also reported. The use of the succinimide heterocycle as a directing group is also demonstrated in modest yields. PMID- 27680399 TI - Rotational friction of dipolar colloids measured by driven torsional oscillations. AB - Despite its prominent role in the dynamics of soft materials, rotational friction remains a quantity that is difficult to determine for many micron-sized objects. Here, we demonstrate how the Stokes coefficient of rotational friction can be obtained from the driven torsional oscillations of single particles in a highly viscous environment. The idea is that the oscillation amplitude of a dipolar particle under combined static and oscillating fields provides a measure for the Stokes friction. From numerical studies we derive a semi-empirical analytic expression for the amplitude of the oscillation, which cannot be calculated analytically from the equation of motion. We additionally demonstrate that this expression can be used to experimentally determine the rotational friction coefficient of single particles. Here, we record the amplitudes of a field-driven dipolar Janus microsphere with optical microscopy. The presented method distinguishes itself in its experimental and conceptual simplicity. The magnetic torque leaves the local environment unchanged, which contrasts with other approaches where, for example, additional mechanical (frictional) or thermal contributions have to be regarded. PMID- 27680401 TI - Anatomical considerations for the management of a left-sided superior caval vein draining to the roof of the left atrium. AB - : Aims The pathophysiological entity of a persisting left-sided superior caval vein draining into the roof of the left atrium represents an extreme form of coronary sinus de-roofing. This is an uncommon, but well-documented condition associated with systemic desaturation due to a right-to-left shunt. Depending on the size of the coronary ostium, the defect may also present with right-sided volume loading. We describe two patients, both of whom presented with desaturation, and highlight the important anatomical features underscoring management. Methods and Results Both patients were managed interventionally with previous assessment of the size of the coronary sinus ostium through cross sectional imaging. This revealed a restrictive interatrial communication at the right atrial mouth of the coronary sinus in both patients, which permitted an interventional approach, as the residual left-to-right shunt subsequent to closure of the aberrant vessel would be negligible. At intervention, test occlusion of the left superior caval vein allowed assessment of decompressing vessels before successful occlusion using an Amplatzer Vascular Plug. CONCLUSIONS: Persistence of a left superior caval vein draining to the left atrium may be associated with an interatrial communication at the mouth of the unroofed coronary sinus. The ostium of the de-roofed coronary sinus can be atretic, restrictive, normally sized, or enlarged. Careful assessment of the size of this defect is required before treatment. In view of its importance, which has received little attention in the literature to date, we suggest an additional consideration to the classification of unroofed coronary sinus. PMID- 27680402 TI - From leaves to landscape: A multiscale approach to assess fire hazard in wildland urban interface areas. AB - The overlapping zone between urbanization and wildland vegetation, known as the wildland urban interface (WUI), is often at high risk of wildfire. Human activities increase the likelihood of wildfires, which can have disastrous consequences for property and land use, and can pose a serious threat to lives. Fire hazard assessments depend strongly on the spatial scale of analysis. We assessed the fire hazard in a WUI area of a Patagonian city by working at three scales: landscape, community and species. Fire is a complex phenomenon, so we used a large number of variables that correlate a priori with the fire hazard. Consequently, we analyzed environmental variables together with fuel load and leaf flammability variables and integrated all the information in a fire hazard map with four fire hazard categories. The Nothofagus dombeyi forest had the highest fire hazard while grasslands had the lowest. Our work highlights the vulnerability of the wildland-urban interface to fire in this region and our suggested methodology could be applied in other wildland-urban interface areas. Particularly in high hazard areas, our work could help in spatial delimitation policies, urban planning and development of plans for the protection of human lives and assets. PMID- 27680403 TI - Quantitative Nanoscale Magnetic Study of Isolated Diameter-Modulated FeCoCu Nanowires. AB - The comprehension of the magnetic configuration in FeCoCu nanowires with a diameter-modulated cylindrical geometry will allow controlling the domain wall motion in this low-dimensional system under the application of magnetic fields and/or the injection of current pulses. Here we perform a quantitative magnetic characterization of isolated diameter-modulated FeCoCu nanowires by combining nanoscale magnetic characterization techniques such as electron holography, magnetic force microscopy, and micromagnetic simulations. Local reconstructions of the magnetic distribution show the diameter-modulated geometry of the wires induces the formation of vortex-like structures and magnetic charges in the regions where the diameter is varied. Vortex-like structures modify the axial alignment of the magnetization in large-diameter segments. Moreover, the magnetic charges control the demagnetizing field distribution, promoting a flux-closure stray field configuration around large-diameter segments and keeping the demagnetizing field parallel to the NW's magnetization around small diameter segments. The detailed description of the remanent state in diameter-modulated cylindrical FeCoCu nanowires allows us to provide a clear explanation of the origin of bright and dark contrast observed in magnetic force microscopy images, which have the same feature of magnetic domain walls. This work establishes the primary knowledge required for future magnetization reversal studies with the aim of searching efficient modulated geometries that allow an optimum and controlled domain wall propagation. PMID- 27680404 TI - Modification of phage for increased antibacterial effect towards dental biofilm. PMID- 27680405 TI - Biomonitoring Human Exposure to Household Air Pollution and Association with Self reported Health Symptoms - A Stove Intervention Study in Peru. AB - BACKGROUND: Household air pollution (HAP) from indoor biomass stoves contains harmful pollutants, such as polycyclic aromatic hydrocarbons (PAHs), and is a leading risk factor for global disease burden. We used biomonitoring to assess HAP exposure and association with self-reported symptoms in 334 non-smoking Peruvian women to evaluate the efficacy of a stove intervention program. METHODS: We conducted a cross-sectional study within the framework of a community randomized control trial. Using urinary PAH metabolites (OH-PAHs) as the exposure biomarkers, we investigated whether the intervention group (n=155, with new chimney-equipped stoves) were less exposed to HAP compared to the control group (n=179, with mostly open-fire stoves). We also estimated associations between the exposure biomarkers, risk factors, and self-reported health symptoms, such as recent eye conditions, respiratory conditions, and headache. RESULTS: We observed reduced headache and ocular symptoms in the intervention group than the control group. Urinary 2-naphthol, a suggested biomarker for inhalation PAH exposure, was significantly lower in the intervention group (GM with 95% CI: 13.4 [12.3, 14.6] MUg/g creatinine) compared to control group (16.5 [15.0, 18.0] MUg/g creatinine). Stove type and/or 2-naphthol was associated with a number of self-reported symptoms, such as red eye (adjusted OR with 95% CI: 3.80 [1.32, 10.9]) in the past 48h. CONCLUSIONS: Even with the improved stoves, the biomarker concentrations in this study far exceeded those of the general populations and were higher than a no-observed-genotoxic-effect-level, indicating high exposure and a potential for increased cancer risk in the population. PMID- 27680406 TI - Disparities in chronic medical conditions in the Mid-South. AB - OBJECTIVE: This study examined differences in socio-demographic characteristics and health behaviors relevant to chronic medical conditions (CMCs) in the Mid South region (Alabama, Mississippi, Louisiana, Kentucky, Tennessee, and Arkansas), and identified subpopulations with increased burden of chronic disease. METHODS: Data were obtained from the 2013 Behavioral Risk Factor Surveillance System. The top five most prevalent CMCs in the Mid-South were analyzed: asthma, high blood pressure (HBP), obesity, arthritis, and depression. Adjusted odds ratios (AOR) and confidence intervals (CI) of race-gender combinations were estimated using logistic regression. Differences in associations between socio-demographic characteristics and CMCs according to income were also examined. RESULTS: The weighted prevalence estimates of the top five CMCs ranged from 66% (asthma) to 20% (depression). Higher income and employment were associated with better outcomes in all five CMCs. Higher educational attainment and physical activity were associated with better HBP, obesity, and arthritis status. Black and white females had higher odds of asthma compared to white males (black AOR = 1.7, CI: 1.1-2.6, white AOR = 1.7, CI: 1.3 2.2). Black males had lower odds of arthritis (AOR = 0.8, CI: 0.6-0.9), while white females had higher odds (AOR = 1.3, CI: 1.2-1.4). Similarly, the odds of depression were lower among black males (AOR = 0.5, CI: 0.4-0.6) and higher among white females (AOR = 2.2, CI: 2.0-2.5). Income-related differences by race were observed for HBP and obesity. CONCLUSION: Disparities in CMCs are associated with income and disproportionately affect the black population. In the Mid-South, race and gender disparities in the top five chronic conditions are more prominent among higher-income rather than lower-income individuals. PMID- 27680407 TI - Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis. AB - BACKGROUND: Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). METHODS: This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. FINDINGS: Analysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23-84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval [CI] 25-45). In the ITT population, median PFS was 4.1 months (95% CI 3.6-5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4-28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1-11.0) and 5.1 months (95% CI 3.3-5.5), respectively, and median OS was 28.0 months (95% CI 7.6 not estimable) and 24.2 months (95% CI 15.8-32.8), respectively. Common grade >2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%). INTERPRETATION: Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour. PMID- 27680408 TI - Corrigendum to "Immunohistochemical subtypes predict survival in metastatic breast cancer receiving high-dose chemotherapy with autologous haematopoietic stem cell transplantation" [Eur J Cancer 57 (April 2016) 118-126]. PMID- 27680409 TI - Simultaneous surface-adsorbed organic matter desorption and cell integrity maintenance by moderate prechlorination to enhance Microcystis aeruginosa removal in KMnO4Fe(II) process. AB - The KMnO4Fe(II) process was proved to have good application potential in Microcystis aeruginosa removal, although at relatively high doses. This study aims to improve the algae removal in KMnO4Fe(II) process by moderate prechlorination, which can realize the desorption of surface-adsorbed organic matter (S-AOM) from algae cells without damaging cell integrity. S-AOM was proved to not only inhibit algae removal but also maintain cell integrity, using various dilution methods for algal suspension preparation. The dilution after filtration method mainly removed the dissolved organics in cultured M. aeruginosa, while the dilution after centrifugal cleaning method could also remove the S-AOM on algae cells. Compared with the S-AOM-removed algal suspension, the lower algae removal in KMnO4Fe(II) process and the reduced proportion of damaged cells during prechlorination of algal suspension without S-AOM removed indicated the inhibitory role of S-AOM in algae removal and the protective function of S-AOM toward cell integrity, respectively. Moderate prechlorination of directly diluted M. aeruginosa could be realized at chlorine doses of below 0.5 mg/L, and the damaged cell ratios were below 4% after 5-min prechlorination. The ability of the KMnO4Fe(II) process to remove algae was dramatically enhanced by the elevation of chlorine dose from 0 to 0.5 mg/L, as more S-AOM was desorbed during prechlorination. Additionally, algae cells were easily captured by flocs after moderate prechlorination, which benefited the floc aggregation for formation of tightly bounded algae flocs. Therefore, the desorption of S-AOM without damaging cell integrity is the key feature of moderate prechlorination, which can be applied in improving the algae removal of KMnO4Fe(II) process. PMID- 27680410 TI - Radiological Evaluation of Artificial Stone Silicosis Outbreak: Emphasizing Findings in Lung Transplant Recipients. AB - OBJECTIVE: The aim of this study was to describe the computed tomography (CT) findings and correlate pulmonary function tests (PFTs) of silicosis patients with emphasis on the findings in lung transplantation (LTX) recipients. METHODS: We studied the chest CT scans from 82 marble workers exposed to artificial stone dust and who had a diagnosis of silicosis, of whom 13 patients underwent LTX. Silicosis-associated findings were graded and correlated to concomitant PFT. RESULTS: A statistically significant inverse relationship was found between chest CT scores and PFT including forced expired volume in the first second (r = -0.54, P < 0.0001), total lung capacity (r = -0.4, P < 0.0001), and diffusion capacity for carbon monoxide single breath % (r = -0.6, P < 0.0001) parameters. Progressive massive fibrosis indicating advanced and complicated silicosis was found in 85% of LTX patients, as compared with 40% in patients with maintained pulmonary function. Ground-glass opacities were seen in some LTX patients with or without signs of progressive massive fibrosis. Two of these patients had silicoproteinosis diagnosed within the resected lung, indicating an acute or accelerated form of silicosis. CONCLUSIONS: This silicosis current outbreak is important because of the worldwide use of this and similar high-silica-content, artificial stone products, which can cause progressive severe forms of silicosis. Along with standard clinical assessment and PFT, CT parameters are indicative measures of the disease severity. PMID- 27680411 TI - Evaluation of Hepatocellular Carcinoma Tumor Response After Transcatheter Arterial Chemoembolization Using Gadobenate Dimeglumine-Enhanced Liver Magnetic Resonance. AB - OBJECTIVE: Use of gadobenate dimeglumine-enhanced liver magnetic resonance (MR) for evaluation of hepatocellular carcinoma tumor response after transcatheter arterial chemoembolization (TACE). METHODS: Forty-five patients with hepatocellular carcinoma were imaged with multiphase gadobenate dimeglumine enhanced MR examination at baseline and 1-month follow-up after TACE. Nodule size, enhancement, and apparent diffusion coefficient were measured for both examinations by 2 reviewers. Changes in tumor nodule size, enhancement, and apparent diffusion coefficient were evaluated using the Student t test. RESULTS: Nineteen of 45 patients completed the study, and a total of 34 hepatocellular carcinoma nodules were analyzed. On the posttreatment follow up, there was no significant change in nodule size. Target lesions demonstrated significant decrease in tumor enhancement after TACE (P < 0.001). Intense contrast accumulation along the periphery of the presumed necrotic tumor on the delayed hepatobiliary phase helped to differentiate viable from non-viable tumor. CONCLUSION: Gadobenate dimeglumine-enhanced liver MR may help differentiate between viable and necrotic tumor after TACE. PMID- 27680412 TI - Multidetector Computed Tomography Evaluation of Mesenteric Venous Thrombosis Following Laparoscopic Bariatric Surgery. AB - OBJECTIVE: The purpose of this study is to review multidetector computed tomography (CT) imaging findings of mesenteric venous thrombosis occurring following bariatric surgery. To our knowledge, this complication has not been described in the radiologic literature. METHODS: Multidetector CT examinations of 6 patients known to have developed mesenteric venous thrombosis after laparoscopic bariatric surgery were reviewed. The thrombus was characterized, and associated imaging findings including presence of mesenteric edema, small bowel edema, and thrombotic complications were described. RESULTS: Four patients underwent laparoscopic sleeve gastrectomy approximately 12 days before CT diagnosis of mesenteric thrombosis and 2 patients had a laparoscopic Roux-en-Y gastric bypass approximately 11 years before imaging diagnosis of mesenteric thrombosis.The thrombus occupied the entire length of the superior mesenteric vein in all cases. Extension into jejunal branches was present in 4 cases. The thrombus was completely occlusive in 4 of 6 patients. CONCLUSIONS: Mesenteric venous thrombosis is an increasingly recognized complication of laparoscopic bariatric surgery. Awareness demands that postbariatric surgery patients with acute abdominal pain be studied with intravenous contrast material. PMID- 27680413 TI - Does Acromion Morphology Depend on the Extremity or on Gender in the Population? AB - OBJECTIVE: The aims were to study the acromion parameters in the population and to assess the extremity or sex variation in the acromion morphology. METHODS: The lateral acromion angle (LAA) and the acromion index (AI) were assessed in a computed tomographic scan database of 250 individuals in the age group of 20 to 49 years. For the analysis of LAA and AI, 286 and 234 shoulders were available, respectively. RESULTS: The LAA was 73.6 +/- 6.6 degrees; 73.7 +/- 6.9 and 72.5 +/ 6.1 degrees for the right and left shoulder, respectively. The AI was 0.755 +/- 0.12; 0.82 +/- 0.12 and 0.69 +/- 0.12 for the left and the right shoulder, respectively. The AI of the right shoulder was significantly different between the 2 sexes (P = 0.04). The difference in the AI and the LAA of the right and left shoulders was significant (P < 0.0001, P = 0.04). CONCLUSIONS: The morphology of the acromion differs between the right and the left shoulders as well as between sexes. PMID- 27680414 TI - Computation of Calcium Score With Dual-Energy Computed Tomography: A Phantom Study. AB - Dual-energy computed tomography (DECT) improves material and tissue characterization compared with single-energy CT; we sought to validate coronary calcium quantification in advancing cardiovascular DECT. In an anthropomorphic phantom, agreement between measurements was excellent, and Bland-Altman analysis demonstrated minimal bias. Compared with the known calcium mass for each phantom, calcium mass by DECT was highly accurate. Noncontrast DECT yields accurate calcium measures and warrants consideration in cardiac protocols for additional tissue characterizations. PMID- 27680415 TI - Magnetic Resonance Imaging Features of Intramedullary Schwannomas. AB - OBJECTIVE: To identify the magnetic resonance imaging features of intramedullary spinal schwannomas. METHODS: Clinical and magnetic resonance imaging findings of 8 patients with pathologically confirmed intramedullary schwannomas were reviewed. RESULTS: There were 6 male and 2 female patients (mean age, 49 years). Tumors were located in the cervical cord (2), the thoracic cord (5), and the cervicothoracic cord (1). Most were in the dorsolateral spinal cord and limited to one side. Expansion of the cord was observed. The majority were hypointense on T1-weighted images and hypo-hyperintense on T2-weighted images. Peritumoral edema was easily found. Gadolinium enhancement was obviously. No recurrence was seen during the follow-up period. CONCLUSIONS: A tumor located in the dorsolateral spinal cord, causing expansion of the cord, with hypointense areas on T2-weighted and obviously enhancement, should arise suspicion of an intramedullary schwannoma. PMID- 27680416 TI - Acute Symptomatic Hyponatremia After Computed Tomography Renal Protocol. AB - Computed tomography (CT) is a widely used imaging modality. Although hyponatremia after CT imaging is rare, its effects can be devastating. Hyperosmolar radiocontrast acts as effective osmoles and causes fluid migration from intracellular into extracellular compartment. Dilutional hyponatremia will ensue if translocation of fluid is in excess of diuresis. This case report detailed an unusual case of acute symptomatic hyponatremia after CT renal protocol and the treatments given after its recognition. PMID- 27680417 TI - Computed Tomography Study of the Feet of Mummy of Ramesses III: New Insights on the Harem Conspiracy. AB - OBJECTIVE: A previous study of the computed tomography (CT) of the neck of mummified Ramesses III (1190-1070 BC) suggested that an assailant slit the Pharaoh's throat with a knife in the plot known as Harem conspiracy. We hypothesized the presence of other injuries in the Pharaoh's body as a result of this fatal attack. METHODS: We analyzed CT images of mummified Ramesses III and reported any finding suggestive of trauma in correlation with archeologic literature. RESULTS: Computed tomographic images show partially amputated left big toe. The bony edges are sharp without signs of attempted healing. The ancient embalmers replaced the missing toe with a linen-made prosthesis and placed 6 metallic amulets (eye of Horus) at the feet region. CONCLUSIONS: The Pharaoh's left big toe was likely chopped perimortem by an assailant using a heavy sharp instrument as an ax. This additional injury supports the plot and gives more information about the death scene. PMID- 27680418 TI - Contrast-Enhanced High-Pitch Computed Tomography in Pediatric Patients Without Electrocardiography Triggering and Sedation: Comparison of Cardiac Image Quality With Conventional Multidetector Computed Tomography. AB - OBJECTIVE: The aim of this study was to compare image quality of anatomical cardiac details without electrocardiography triggering, sedation, or heart rate regulating drugs in contrast-enhanced pediatric chest computed tomography (CT), using high-pitch CT (HPCT) versus conventional pitch-mode technique (multidetector CT [MDCT]). METHODS: After written informed consent, 55 patients (median age, 11 years; range, 3-17 years) were prospectively included in this institutional review board-approved study. Patients underwent clinically indicated, contrast-enhanced MDCT or HPCT of the chest.Image quality was assessed evaluating morphological criteria on a 3-point scale (from 1, high, to 3, low detail) and summed up in a global score (from 4, best, to 12, poor image quality). Artifacts were analyzed correspondingly (from 3, low, to 9, severe artifacts). Effective dose and size-specific dose estimate were calculated for all scans. RESULTS: Cardiac image quality was higher in HPCT than in MDCT (7.1 [1.6] vs 8.8 [1.9], P < 0.001). Nevertheless, HPCT showed limitations in image quality, especially concerning the heart valves (2.5 [0.6] and 1.7 [0.5]) and coronary arteries (1.8 [0.6). Artifact score (3.4 [0.6 vs 5.1 [0.9, P < 0.001), effective dose (1.6 [1.3] vs 2.3 [1.6] mSv, P = 0.047), and size-specific dose estimate (2.5 [1.7] vs 4.1 [2.3] mGy, P = 0.002) were lower in HPCT compared with those in MDCT. CONCLUSIONS: In pediatric patients, contrast-enhanced HPCT of the chest provides high image quality without electrocardiography triggering or sedation, although image quality is somewhat limited for a detailed depiction of cardiac anatomy. PMID- 27680419 TI - Noise Power Characteristics of a Micro-Computed Tomography System. AB - OBJECTIVE: The aim of this study was to investigate the noise power properties of a micro-computed tomography (micro-CT) system under different operating conditions. METHODS: A commercial micro-CT was used in the study that used a flat panel detector with a 127-MUm-pixel pitch and a micro-focus x-ray tube. Conical tubes of various diameters were used under different acquisition conditions. Multidimensional noise power spectrums were used as a metric to investigate the noise properties of the system. Noise power spectrum was calculated from the difference data generated by subtraction of 2 identical scans. The noise properties with respect to various parameters that include the impact of number of projections, x-ray spectra, milliampere-second, slice location, object diameter, voxel size, geometric magnification (M), back-projection filters, and reconstruction magnification (Mrecon) were studied. RESULTS: At a same isocentric exposure rate of 270 mR/s, the noise power was much lower for the image reconstructed with 3672 views (122 seconds) as compared with the 511 views (17 seconds), whereas at a fixed isocentric exposure of 4600 mR, the noise power levels were almost similar. Image noise with a 50-kV beam was higher as compared with the 90-kV beam at a same isocentric exposure. Image noise from a 16-mm diameter conical tube was much lower as compared with the 28- and 56-mm tubes under identical isocentric exposures. The choice of back-projection filter influences noise power spectrum curves in terms of width and amplitudes. Reconstruction magnification applied during the reconstruction process increased the noise power at lower spatial frequencies but reduced the noise power at higher spatial frequencies. It can be established that, for small details corresponding to high spatial frequencies, reconstruction magnification can provide an improved signal-to-noise ratio. At all spatial frequencies, the in plane images had lower noise power levels as compared with the z-plane images. CONCLUSIONS: The noise power properties investigated in this study provide important image quality references for refined cone beam system development, optimization, and operations. PMID- 27680420 TI - Effect of Coronary Artery Calcification Score by Lifestyle and Correlation With Coronary Artery Stenosis by Multidetector Computed Tomography. AB - OBJECTIVE: This study examined the effect of coronary artery calcification score by lifestyle and correlation with coronary artery stenosis in persons who underwent coronary artery computed tomography (CT) angiography among health examinees for heart diseases in Korea. METHODS AND MATERIALS: The study included 506 subjects (256 men and 250 women) who underwent coronary artery CT angiography among health examines for heart diseases at the Incheon Branch of the Korea Association of Health Promotion between January 2, 2014, and December 31, 2014. The demographical variables of the subjects were determined by frequency analysis, and the difference by sex was compared and analyzed using chi independence test. Independent 2-sample t test was performed to determine any difference in main factors by coronary artery calcification. RESULTS: According to the results, 175 (34.6%) had calcification, men showed statistically higher scores than women, and calcification seemed higher in those who were older, taller, heavier, and thicker in waist. Regarding blood pressure, calcification was shown if contraction phase and relaxation blood pressure was higher, blood sugar before meal was higher, and neutral fat was higher. By lifestyle, calcification seemed to be higher in those with more alcohol drinking per week, long past smoking years, and higher smoking amount per day in the past and present. In addition, coronary artery stenosis rate showed statistical correlation with calcification from the left anterior descending artery, right coronary artery, left circumflex artery, and left main coronary artery in sequence. CONCLUSIONS: In conclusion, coronary artery calcification score CT is deemed to be a suitable method for the estimation of coronary artery stenosis with short examination time, low radiation exposure, and noninvasive method. PMID- 27680422 TI - Feasibility and benefits of computerized cognitive exercise to adults with chronic moderate-to-severe cognitive impairments following an acquired brain injury: A pilot study. AB - PRIMARY OBJECTIVE: The purpose of this pilot study was to explore feasibility and effects of participation in a computerized cognitive fitness exercise program by a group of adults with chronic moderate-to-severe cognitive impairments following an acquired brain injury (ABI). RESEARCH DESIGN: This study used a mixed methods design with a convenience sample of individuals forming two groups (+/- exercise). METHODS AND PROCEDURES: Following neurocognitive and satisfaction with life pre-testing of 14 participants, seven were enrolled in a 5-month, 5-days a week computerized cognitive exercise program. Post-testing of all participants and semi-structured interviews of exercise group participants were completed. MAIN OUTCOMES AND RESULTS: It was feasible for adults with chronic moderate-to severe cognitive impairments post-ABI to participate in a computerized cognitive exercise program with ongoing external cues to initiate exercise sessions and/or to complete them as needed. Significant exercise group improvements were made on memory and verbal fluency post-tests and life satisfaction. The majority of exercise group participants reported some degree of positive impact on cognitive abilities and some on everyday functioning from program participation. CONCLUSIONS: Adults with chronic moderate-to-severe cognitive impairments following an ABI may benefit from participation in computerized cognitive exercise programs. Further study is warranted. PMID- 27680421 TI - Computed Tomography and Magnetic Resonance Imaging Characteristics of Peripheral Primitive Neuroectodermal Tumor: A Retrospective Analysis of 16 Cases. AB - PURPOSE: The aim of this study was to analyze the radiological features of peripheral primitive neuroectodermal tumor (pPNET). MATERIALS AND METHODS: The radiological and clinical findings for 16 patients with pPNETs were retrospectively reviewed. The 16 tumors were classified into 4 groups (meninges group, n = 4; spine group, n = 3; bone group, n = 5; soft-tissue group, n = 4), and clinical data, size, and common and unique CT/MRI characteristics were assessed. RESULTS: Peripheral primitive neuroectodermal tumors presented as large solid masses with aggressive extension into the neighboring tissue. Most tumors (11/16) presented with necrosis, and 5 of the 16 cases showed signs of hemorrhage. The "dural tail sign" was observed in the meninges and spine groups. The pPNETs of bone demonstrated bony destruction with spiculated periosteal reaction, and small nourishing vessels were found in tumors in the soft-tissue group. CONCLUSIONS: Peripheral primitive neuroectodermal tumor should be suggested as an important differential diagnosis when the tumor presents as a large, ill-defined solid mass with aggressive extension and significant enhancement. PMID- 27680424 TI - Twitter and Cardiovascular Disease: Useful Chirps or Noisy Chatter? PMID- 27680423 TI - Micellar dipolar rearrangement is sensitive to hydrophobic chain length: Implication for structural switchover of piroxicam. AB - The interfacial properties of the membrane are exceptionally vital in drug membrane interaction. They not only select out a particular prototropic form of the drug molecule for incorporation, but are also potent enough to induce structural switchover of these drugs in several cases. In this work, we quantitatively monitored the change in dipolar rearrangement of the micellar interface (as a simplified membrane mimic) by measuring the dielectric constant and dipole potential with the micellization of SDS at pH 3.6. The dielectric constant and dipole potential were measured utilizing the fluorescence of polarity sensitive probe, pyrene and potential-sensitive probe, di-8-ANEPPS, respectively. Our study demonstrates that the change in dipolar rearrangement directly influences the switchover equilibrium between the anionic and neutral from of piroxicam. We have further extended our work to evaluate the effect of hydrophobic chain length of the surfactants on the dipolar rearrangement and its effect on the structural switchover of piroxicam. It is interesting that the extent of switchover of piroxicam is directly correlated with the dipolar rearrangement induced bythe varying hydrophobic chain length of the surfactants. To the best of our knowledge, our results constitute the first report to show the dependence of dipole potential on the hydrophobic chain length of the surfactant and demonstrate that the dipolar rearrangement directly tunes the extent of structural switchover of piroxicam, which was so far only intuitive. We consider that this new finding would have promising implication in drug distribution and drug efficacy. PMID- 27680426 TI - Perceived Exertion Is Lower When Using a Functional Electrical Stimulation Neuroprosthesis Compared With an Ankle-Foot Orthosis in Persons With Multiple Sclerosis: A Preliminary Study. AB - OBJECTIVE: This study investigates the direct comparison of energy cost, efficiency, and effort between an ankle-foot orthosis (AFO) and a functional electrical stimulation (FES) device for foot drop in ambulatory patients with multiple sclerosis. DESIGN: Twenty adults (32-74 years old; 55% female) with a diagnosis of multiple sclerosis resulting in foot drop participated in a crossover, counterbalanced preliminary study. Each participant was tested on different days, with each session consisting of a separate walk trial per prosthetic device. Heart rate, oxygen consumption, speed, distance, and self reported exertion were measured independently for each device walk trial. Repeated-measures analysis of variance with device and visit number as within participants independent variables were run for the primary outcome variables of perceived exertion, energy, and metabolic efficiency. RESULTS: A significant main effect of device was found for perceived exertion (P = 0.01), with participants reporting decreased exertion levels (Borg Scale) when using the FES compared with the AFO (mean difference, 1.63; 95% confidence interval, 0.49-2.76). Energy and efficiency did not significantly differ by device. CONCLUSION: Results suggest that further investigation of the potential advantages of FES devices over traditional AFO is warranted. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) describe the potential differences between an AFO and FES for the treatment of foot drop in patients with multiple sclerosis, (2) understand the mechanisms and prevalence of foot drop in patients with multiple sclerosis, and (3) recognize the potential benefit of improved perceived exertion found when using FES for the treatment of foot drop in patients with multiple sclerosis. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. PMID- 27680425 TI - Evaluating the costs and benefits of pneumococcal vaccination in adults. AB - INTRODUCTION: Pneumococcal infection is a public health concern that disproportionately affects the young, the elderly, and the immunocompromised. There is an open debate on the implementation of polysaccharide and/or conjugate vaccines for pneumococcal diseases in adults and the elderly in many countries. The aim of this paper is to systematically review the economic profile of pneumococcal vaccines in adults in terms of costs and benefits. Areas covered: The search for economic studies on pneumococcal vaccination was carried out in Pubmed, Embase, Scopus, and the HTA and NHS EED databases and through a manual search in journals dealing with economic evaluations. We included original articles and reviews with economic evaluation of polysaccharide 23-valent (PPV23) and/or conjugate pneumococcal vaccine 13-valent (PCV13) use in adults, the elderly, and at-risk groups to provide a systematic review of economical evaluation. Expert commentary: Pneumococcal vaccination is strongly recommended for all adults, especially subjects at risk and the elderly. Pneumococcal vaccination with PCV13 or PPV23 in adults is good value for money and should be a priority for the decision-makers. The main issue is how vaccination could be offered. PMID- 27680427 TI - Kilohertz and Low-Frequency Electrical Stimulation With the Same Pulse Duration Have Similar Efficiency for Inducing Isometric Knee Extension Torque and Discomfort. AB - OBJECTIVE: To test the hypotheses that, as compared with pulsed current with the same pulse duration, kilohertz frequency alternating current would not differ in terms of evoked-torque production and perceived discomfort, and as a result, it would show the same current efficiency. DESIGN: A repeated-measures design with 4 stimuli presented in random order was used to test 25 women: (1) 500-microsecond pulse duration, (2) 250-microsecond pulse duration, (3) 500-microsecond pulse duration and low carrier frequency (1 kHz), (4) 250-microsecond pulse duration and high carrier frequency (4 kHz). Isometric peak torque of quadriceps muscle was measured using an isokinetic dynamometer. Discomfort was measured using a visual analog scale. RESULTS: Currents with long pulse durations induced approximately 21% higher evoked torque than short pulse durations. In addition, currents with 500 microseconds delivered greater amounts of charge than stimulation patterns using 250-microsecond pulse durations (P < 0.05). All currents presented similar discomfort. There was no difference on stimulation efficiency with the same pulse duration. CONCLUSIONS: Both kilohertz frequency alternating current and pulsed current, with the same pulse duration, have similar efficiency for inducing isometric knee extension torque and discomfort. However, neuromuscular electrical stimulation (NMES) with longer pulse duration induces higher NMES-evoked torque, regardless of the carrier frequency. Pulse duration is an important variable that should receive more attention for an optimal application of NMES in clinical settings. PMID- 27680428 TI - Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations. AB - Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (<100 nm). It is applied in food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO2 NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO2 NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO2, particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO2 (NPs) in animals are recommended to refine this assessment. PMID- 27680432 TI - Cycle of service cuts. AB - Strikes, rallies, low morale, bed closures, cuts and longer waiting lists - all of the ingredients of the 1987 winter of discontent that led to the government's review of the provision of health care in the National Health Service. PMID- 27680429 TI - Association Between Continued Cannabis Use and Risk of Relapse in First-Episode Psychosis: A Quasi-Experimental Investigation Within an Observational Study. AB - Importance: Cannabis use after first-episode psychosis is associated with poor outcomes, but the causal nature of this association is unclear. Objective: To examine the precise nature of the association between continued cannabis use after the onset of psychosis and risk of relapse of psychosis. Design, Setting, and Participants: This prospective cohort study followed up for at least 2 years after the onset of psychosis 220 patients who presented to psychiatric services in South London, England, from April 12, 2002, to July 26, 2013, with first episode psychosis. Longitudinal modeling (fixed-effects analysis, cross-lagged path analysis) was used to examine whether the association between changes in cannabis use and risk of relapse over time is the result of shared vulnerability between psychosis and cannabis use, psychosis increasing the risk of cannabis use (reverse causation), or a causal effect of cannabis use on psychosis relapse. Interventions: Exposure to cannabis within the first and second years after onset of psychosis. Main Outcomes and Measures: The main outcome measure was relapse of psychosis, defined as subsequent hospitalization for psychosis. Effect of cannabis use status in the first year (Ct1) and second year (Ct2) and pattern of cannabis use continuation in the first year and second year were modeled for risk of relapse in the first year (Rt1) and risk of relapse in the second year (Rt2) after psychosis onset. Results: A total of 220 patients with first-episode psychosis were included in the analysis (mean [SD] age, 28.62 [8.58] years; age range, 18-65 years; 90 women [40.9%] and 130 men [59.1%]). Fixed-effects models that adjusted for time-variant (other illicit drug use, antipsychotic medication adherence) and time-invariant (eg, genetic or premorbid environment) unobserved confounders revealed that there was an increase in the odds of experiencing a relapse of psychosis during periods of cannabis use relative to periods of no use (odds ratio, 1.13; 95% CI, 1.03-1.24). Change in the pattern of continuation significantly increased the risk (odds ratio, 1.07; 95% CI, 1.02-1.13), suggesting a dose-dependent association. Cross-lagged analysis confirmed that this association reflected an effect of cannabis use on subsequent risk of relapse (Ct1->Rt2: beta = 0.44, P = .04) rather than an effect of relapse on subsequent cannabis use (Rt1->Ct2: beta = -0.29, P = .59). Conclusions and Relevance: These results reveal a dose-dependent association between change in cannabis use and relapse of psychosis that is unlikely to be a result of self medication or genetic and environmental confounding. PMID- 27680433 TI - Unions denounce 'attack' on elderly. AB - Unions fear up to 1,500 nursing posts in Scotland could be hit by government plans to cut staffing on elderly care wards. PMID- 27680430 TI - Recto-Urinary Fistula (RUF) treated by Transanal Endoscopic Microsurgery (TEM) Review of the literature and surgical technique. AB - AIM: Recto-Urinary Fistula (RUF) is a rare complication of pelvic surgery. Different approaches are reported in literature but a gold standard treatment has not yet been achieved. Transanal Endoscopic Microsurgery (TEM) is a miniinvasive approach with well known advantages as magnification, 3D view and lighting of the operative field. Aim of the present review is to report the current evidence in literature about technique and results of RUF treatment by TEM and to suggest some key points for its correct management. MATERIALS OF STUDY: After a medline in Pubmed and Scopus databases, seven papers were eligible for the present study. Data were reviewed on the basis of the cases reported, patient's characteristics, surgical techniques and results. RESULTS: Eighteen cases have been reported in the literature from 1996 to 2005. The healing success rate was 77.8%. Fecal and urinary diversion were performed before TEM-assisted procedure in the 83% and 94% of cases, respectively. Recurrence was observed in four patients (22%). DISCUSSION: A gold standard treatment of RUF should ensure the complete removal of scar tissue around the fistula, in order to perform a tension free suture on healthy margins with adequate vascularization. Preoperative stoma improves the healing of the fistula, reducing local inflammation and infections. CONCLUSIONS: There is not common view of this topic in literature and clarify which could be the best treatment is a key condition due to high failure rate of the surgical proposed techniques. Recurrences treatment has a lower cure rate if compared to primary lesions, nevertheless more studies are required to confirm this data. KEY WORDS: Recto-Urinary Fistula (RUF), Transanal Endoscopic Microsurgery (TEM), Transanal approach. PMID- 27680435 TI - Project 2000 nurse wins landmark appeal. AB - Project 2000-trained nurses will not be denied financial assistance from local education authorities following a landmark appeal by a Newcastle nurse. PMID- 27680436 TI - Services increased after cancer tragedy. AB - Support services for nurses working at the Royal Orthopaedic Hospital in Birmingham have been stepped up following the release of a report which says 42 patients were wrongly treated for cancer. PMID- 27680434 TI - London crisis could spread to rest of UK. AB - The postponement of nonurgent operations at London hospitals signals the start of a 'domino effect' which could plunge hospitals around the country into financial crises and cause nursing cutbacks, unions have warned. PMID- 27680437 TI - Authorship guidelines agreed. AB - Guidelines on authorship and dealing with fraudulent publication have been agreed by the International Academy of Nursing Editors at its annual meeting held recently in Alberta, Canada. PMID- 27680438 TI - ? AB - Health and safety: Health Minister Dr Brian Mawhinney meets five year-old Adis Avdic, one of the Bosnian children evacuated from Sarajevo as part of 'Operation Irma', and his mother. Amelia, at Stoke Mandeville Hospital. PMID- 27680439 TI - 'Home alone' cases growing. AB - Cutbacks in day nursery provision and the increasing cost of private day care for children are contributing to the growing number of 'home alone' cases, the Health Visitors' Association claimed last week. PMID- 27680441 TI - Nursing Standard on the increase. AB - Nursing Standard's first audited readership figures show an average circulation of 54,449 per issue for the first six months of the year. PMID- 27680440 TI - 'Training needed' in family planning. AB - Too few practice nurses have had formal training in giving advice on family planning and sexual health and those who have are sometimes under-used, according to the Family Planning Association. PMID- 27680443 TI - Misusers 'slipping through the net'. AB - Alcohol and drug misusers who cannot find residential care are slipping through the net of community-based services, says a new survey. PMID- 27680444 TI - Redundancy threats for nursing posts in SW Hampshire. AB - Nurses at a Hampshire hospital face redundancy, the RCN said last week, after Southampton and SW Hampshire HA withdrew its contract. PMID- 27680445 TI - Female managers criticised. AB - Female managers in the NHS have been criticised for their management techniques by the men working for them, a regional health authority survey has revealed. But the women surveyed saw their female bosses as democrats who put people before tasks. PMID- 27680446 TI - ? AB - Yoga teachers join their guru - BKS Iyengar of Poona, India - In the headstand position at Britain's first Iyengar Yoga Convention at Crystal Palace sports centre. They are among 1000 people from 30 countries who attended the conference, organised to promote the physical and mental benefits of yoga. 'BKS' has been teaching yoga for 58 years and his fans include Felicity Kendal, Yehudi Menuhin and Frank Bruno. PMID- 27680447 TI - Child mental illness 'going undetected'. AB - General practioners are failing to identify thousands of children who are suffering from mental illness and learning disabilities, the Mental Health Foundation has warned. PMID- 27680449 TI - Call for comments on complaints. AB - The committee looking at the handling of complaints about the NHS has appealed for comments from individuals and organisations. PMID- 27680450 TI - ? AB - Old technology: A mechanical steel and ivory chainsaw, was sold for ,423,100 to Thackray Medical Museum in Leeds at a recent Christie's auction of medical instruments. Originally intended for use in amputation, few examples of the chainsaw were ever distributed because it was found to go too far too fast'. PMID- 27680451 TI - No choice for nurses. AB - A CP fundholder who has transferred his community nursing contracts to a different trust wants the community nurses who work with him to he included in the deal. The practice of David Colin-Thome in Runcorn has asked for the community nurses to join the Premier Health Trust based in Staffordshire. PMID- 27680453 TI - ? AB - France One in 10 children tested in Paris have unacceptably high levels of lead in their blood, a study by health authorities reveals. PMID- 27680452 TI - Nursing homes taking in expatriates from Spain. AB - Nursing homes in Britain are taking in elderly people who retired to Spain and are now in need of long-term medical care, according to Age Concern. PMID- 27680454 TI - World news. AB - United States Registered nurses will be a key component of hospital survival in the reformed health care environment because of their contribution to the quality of patient care and the containment of hospital costs, according to the American Nurses Association. PMID- 27680456 TI - Midwives' jobs shortage fears. AB - An international shortage of jobs for newly qualified midwives has prompted Welsh midwives to speak out about their plight. PMID- 27680457 TI - Anglo-French clash over schizophrenia treatment. AB - French and British psychiatrists have differing views on what schizophrenia is and how it should be treated. PMID- 27680459 TI - Study of '90s children reveals shift in practices. AB - A massive data bank on the health and development of children born in the Nineties is already showing intriguing findings since being launched. PMID- 27680460 TI - Nurses should take a lead in alcohol education. AB - Nurses can play a vital role in preventing alcohol misuse, according to Alcohol Concern which says there must be a major boost in public education programmes if the government's Health of the Nation targets are to be met. PMID- 27680461 TI - Natural peptide to help fight the flab? AB - A naturally occurring peptide might help people lose weight, researchers from Lund and Baton Rouge believe. PMID- 27680462 TI - Hospital referrals not changed by GP contract. AB - Despite a sharp increase in minor surgery by GPs there has been no compensatory decrease in hospital referrals, new research suggests. PMID- 27680463 TI - Space gives clues to heart attack deaths. AB - The reason why some people the soon after their first heart attack might be explained by research from the American space programme. PMID- 27680464 TI - Rapid diagnosis of central line sepsis. AB - The number of central venous lines removed for suspected sepsis could be reduced by using a rapid test to detect infection. Researchers from Leeds evaluated three rapid tests to distinguish between infected and non-infected lines by comparing them with quantitative bacteriology. Subjects were 51 children, ranging from premature infants to those aged two years. All central venous lines were dedicated to parenteral nutrition. PMID- 27680465 TI - Banding better than injecting varices. AB - Banding ligation of oesophageal varices results in faster eradication in fewer endoscopy sessions when compared with injection sclerotherapy. PMID- 27680466 TI - Don't be so passive. AB - Action on Smoking and Health (ASH) is campaigning for polite people who suffer passive smoking in silence to speak out. The ASH campaign, Breathing Space, will encourage non-smokers to use their influence as consumers, customers and employees to demand the right to breathe smoke-free air. PMID- 27680467 TI - Chairs on the move. AB - Upping sticks and taking off for far flung places is usually the prerogative of the young, who then return and 'settle down' to domesticity. Sue and Paul Armitage have bucked the trend, are selling up and heading for Australia. PMID- 27680469 TI - Nurses make being mentally ill a crime. AB - My own experience of mental health problems made me very interested to read Geraldine Sweeney-McCabe's letter exploring the reasons why healthcare professionals fail to seek help when in such difficulties (What stops people seeking help?, August 4). PMID- 27680470 TI - Nursing gets sucked up an ivory tower. AB - Trevor Clay's interview with Professor Jane Robinson (Viewpoint, August 18) raised some interesting points on the future of nursing. PMID- 27680468 TI - Don't catch cold from Tory warmth. AB - Nursing must contain more optimists than any other profession. PMID- 27680471 TI - EN-Dangered nurses face extinction. AB - I feel most upset over the way that enrolled nurses are being treated at present. PMID- 27680473 TI - Enrolled nurses have more up top. AB - If, amid all the current debate about the de-skilling and conversion of enrolled nurses, you asked the majority of charge nurses to identify the most important member of the working team, they would tell you that it is the EN. Why? PMID- 27680472 TI - Little differences cause me to blush. AB - Now that we have a new UK Central Council, there is a new opportunity to examine the position of the enrolled nurse. PMID- 27680474 TI - No promotion gained from time in loo. AB - Your clinical article, Elderly toileting: is two-hourly too often? (Clinical, August 11), was disturbing in that the author described incontinence rates of 60 per cent as 'continence promotion'. I view daytime incontinence rates of 60 per cent as a serious problem. PMID- 27680475 TI - Information exchange. AB - * I would be grateful to hear from anyone using massage or any other body work therapy in their work, as I am in the process of compiling a resource centre on massage in nursing. PMID- 27680476 TI - Sluice talk. PMID- 27680477 TI - Catch Me a Nightingale Catch Me a Nightingale J Ash Robert Hale Ltd 202pp L12.95 0-7090-4604-9 [Formula: see text]. AB - Catch Me a Nightingale is a nostalgic biographical account of Joan Ash's 40-year career in nursing. The story starts in 1939 with the author's discovery, while on a church outing to the seaside, that she wants to be a nurse. PMID- 27680478 TI - Children of Alcoholics D Stafford Children of Alcoholics Piatkus 204pp L8.99 0 7499-1140-9. AB - Alcoholic parents cause a tremendous amount of problems for their children. PMID- 27680479 TI - Margaret Newman: Health as Expanding Consciousness Margaret Newman: Health as Expanding Consciousness J Marchione SAGE Publications 52pp L6.95 0-8039-4796-8. AB - In SAGE's series of monographs on nursing models, Joanne Marchione does an excellent definitive work on Newman's model, Health as Expanding Consciousness. To appreciate this book fully, you need to be aware of Newman's texts published in 1978 and 1986. You can easily do a library search, as the work carries an extensive bibliography. PMID- 27680480 TI - The mail snip. AB - Anybody who needs to keep mailing lists of any sort is faced with the question of how to organise all those names and addresses. PMID- 27680481 TI - Immunofluorescence Labeling of a Mutant of Tissue Non-Specific Alkaline Phosphatase Lacking the Glysosylphosphatidylinositol Anchor. PMID- 27680482 TI - Objective Spectrometric Measurement of Keloid Color in the East Asian Population: Pitfalls of Subjective Color Measurements. AB - BACKGROUND: Keloids are characterized by the formation of excessive scar tissue that extends beyond the area of the initial wound. Keloid redness is due to angiogenesis and chronic inflammation and is an important indicator of the severity of the lesion and the effectiveness of treatment. METHODS: The color of 33 untreated keloids from 30 patients was measured with a narrow-band reflectance colorimeter. The erythema and melanin levels in the keloids (Ek and Mk, respectively) were recorded with control data obtained from the flexor aspect of the forearm (Ec and Mc, respectively). The keloid color was also evaluated subjectively. RESULTS: The Ek or Mk values did not vary significantly according to symptom intensity, scar region, patient age, and patient sex. Younger patients (<40 years) and female patients had significantly higher Ek/Ec ratios than did older patients and male patients, respectively. Subjective keloid redness evaluations distinguished keloids with high Ek/Ec ratios from keloids with low Ek/Ec ratios (P<0.0001) but could not distinguish keloids with high Ek from keloids with low Ek. CONCLUSIONS: Subjective evaluations of keloids in Japanese subjects reflected Ek/Ec ratios, which were strongly affected by variation in background skin color. The subjective assessment of the color of keloids or other skin disorders should be performed with caution in Asian populations. PMID- 27680483 TI - Utility of Measurement of Serum Lactate in Diagnosis of Coagulopathy Associated with Peripheral Circulatory Insufficiency: Retrospective Evaluation Using Thromboelastometry from a Single Center in Japan. AB - Recently, serum lactate level rather than systolic blood pressure (sBP) has been widely used to diagnose peripheral circulatory insufficiency, which often leads to coagulopathy with systemic inflammation. However, most of the reported disorders were examined by plasma samples. The aim of this study was to evaluate the utility of serum lactate for detecting coagulopathy with circulatory failure by using thromboelastometry as well as standard coagulation test. 192 adult patients transported to our hospital between January 2013 and September 2014 were enrolled in this retrospective study. The sBP, serum lactate and thromboelastometry (ROTEM((r))) were measured in these patients in the emergency department. All patients were divided into three groups based on serum lactate levels: (1) the severe group (>=4 mmol/L, n=41); (2) the mild group (<4 mmol/L and >=2 mmol/L, n=59); and (3) the normal group (<2 mmol/L, n=92). Patients in the severe group were of a significantly younger age but had lower pH and poor outcome. SBP was significantly lower and heart rates were higher in the severe group than in the other groups. Prolonged PT-INR and APTT were statistically confirmed in the severe group. ROTEM findings in the severe group revealed significantly lower alpha angle, shortened Lysis Onset Time and significantly more cases exhibited hyperfibrinolysis. The same analysis with the cut-off level of sBP at 90 mmHg showed no significant difference in ROTEM findings between the two groups. Abnormal serum lactate levels (>=4.0 mmol/L) properly reflected peripheral circulatory insufficiency and were more closely associated with coagulopathy such as hyperfibrinolysis and hypocoagulability than sBP. PMID- 27680484 TI - Evaluation of Postoperative Pain Control and Quality of Recovery in Patients Using Intravenous Patient-Controlled Analgesia with Fentanyl: A Prospective Randomized Study. AB - AIM: Opioids are increasingly used to control postoperative pain via intravenous patient-controlled analgesia, with several advantages. The present study evaluated the effects of intravenous patient-controlled analgesia with different doses of fentanyl on postoperative pain and on the quality of physical/emotional recovery from surgery and anesthesia. METHODS: We retrospectively reviewed data from 288 patients, and evaluated whether intravenous patient-controlled analgesia with fentanyl correlated with the degree of postoperative pain. We then prospectively studied 47 patients who underwent elective laparoscopic cholecystectomy. The patients were randomized into 2 groups (15 or 30 MUg/mL of fentanyl), and postoperative pain control was compared using a visual analog scale score. Furthermore, the Japanese 40-item quality of recovery (QoR-40J) score (global and dimensional) and Hospital Anxiety and Depression Scale (HADS) were used to assess the quality of recovery from surgery and anesthesia. RESULTS: Of 288 patients, 20% complained of intolerable pain and 18% experienced postoperative nausea and vomiting. In the prospective study, the visual analog scale pain score was lower in the Fentanyl 30 group than in the Fentanyl 15 group (p<0.05) on postoperative day 1. Dimensional QoR-40J pain subscales correlated with both the emotional state subscales (postoperative day 1, p<0.05; day 2, p<0.05) and global QoR-40 scores on both postoperative days (day 1, p<0.05; day 2, p<0.05). CONCLUSION: The postoperative pain as well as the physical and emotional quality of recovery in the patients who underwent laparoscopic cholecystectomy could be alleviated by sufficient doses of opioids. PMID- 27680485 TI - Vigabatrin Therapy for Infantile Spasms in a Case of Cardiofaciocutaneous Syndrome with Cardiac Hypertrophy Developing during Adrenocorticotropic Hormone Treatment. AB - In a patient with cardiofaciocutaneous syndrome complicated by intractable infantile spasms (West syndrome), cardiac hypertrophy developed during adrenocorticotropic hormone treatment. Various types of antiepileptic drugs, intravenous immunoglobulin, thyrotropin releasing hormone, and a ketogenic diet were ineffective in this case. However, vigabatrin both decreased clinical seizures and improved electroencephalogram findings. Although vigabatrin has not been approved for use in Japan, the results in the present case suggest that this drug should be considered as an alternative therapy for cases of infantile spasms associated with syndromes involving cardiomyopathy or its potential risk factors, such as cardiofaciocutaneous syndrome. PMID- 27680486 TI - Cecal Volvulus Following Elective Laparoscopic Cholecystectomy: A Case Report. AB - Cecal volvulus is characterized by torsion of the cecum around its own mesentery. However, cecal volvulus rarely develops soon after elective laparoscopic cholecystectomy. We report on a case of cecal volvulus that developed in a 54 year-old women 1 day after elective laparoscopic cholecystectomy and was successfully treated via colonoscopic decompression. The symptoms gradually improved in conjunction with recovery from postoperative ileus. Whether the incidence of volvulus has increased with the use of laparoscopic procedures, including laparoscopic cholecystectomy, has yet to be determined. Considering the current trend toward minimally invasive surgery, cecal volvulus should be considered in patients who have postoperative abdominal pain and distention. PMID- 27680487 TI - Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, with Primary Manifestation as an Upper Eyelid Swelling. AB - Extranodal natural killer/T-cell lymphoma (ENK/TCL) is most often in the nose or the nasopharynx but can present elsewhere. We report a rare case of ENK/TCL that presented as swelling of an upper eyelid without ocular involvement. A 76-year old man visited our hospital with a swollen lesion of the left upper eyelid which had appeared 2 months earlier. A biopsy of the upper eyelid revealed slight perivascular and periadnexal infiltration of mononuclear cells with dermal edema. Treatment with oral prednisolone at a dosage of 20 mg/day decreased the eyelid swelling. However, 5 months later, exacerbation of the swelling and nasal congestion were observed. A second biopsy of the upper eyelid revealed a diffuse dermal infiltrate composed of mononuclear cells with an angiocentic growth pattern. Immunohistochemical studies and in situ hybridization showed natural killer-lineage antigens (CD56, granzyme B, and T-cell intracellular antigen 1) with expression of Epstein-Barr virus. These findings lead to the diagnosis of ENK/TCL. We treated the patient with radiation therapy (50 Gy) and 3 courses of a regimen including dexamethasone, carboplatin, etoposide, and ifosphamide. This case suggests that ENK/TCL can present with swelling of an upper eyelid as the primary sign of the skin lesion. Swelling of an upper eyelid should be considered in the differential diagnosis of ENK/TCL. PMID- 27680488 TI - Strategies for Pre-Emptive Mid-Air Collision Avoidance in Budgerigars. AB - We have investigated how birds avoid mid-air collisions during head-on encounters. Trajectories of birds flying towards each other in a tunnel were recorded using high speed video cameras. Analysis and modelling of the data suggest two simple strategies for collision avoidance: (a) each bird veers to its right and (b) each bird changes its altitude relative to the other bird according to a preset preference. Both strategies suggest simple rules by which collisions can be avoided in head-on encounters by two agents, be they animals or machines. The findings are potentially applicable to the design of guidance algorithms for automated collision avoidance on aircraft. PMID- 27680489 TI - Trade-Offs in Male Display Activity with Lek Size. AB - In lek mating systems, males aggregate and defend arenas where they display for females; females select and mate with a male and then solely raise their offspring. Generally, female visits and copulations increase and reproductive variance in male mating success declines with lek size. Here we investigate how male display effort changes across a gradient in lek size. We expect male display effort, an energetically expensive activity, will increase with lek size and male rank due to changes in breeding opportunities and competition among males. We test the interaction of male rank and lek size on display effort using the white bearded manakin, Manacus manacus (Aves: Pipridae), a well-studied species with a wide geographic distribution in the new world tropics. We used mini-video recorders to simultaneously capture female visits and display behaviors of 41 males distributed over 10 leks. We found that overall display effort increased disproportionately with lek size due to males of both high and low ranks increasing their display effort at larger leks. Our results suggest that increased breeding opportunities and intrasexual competition at larger leks result in males of different ranks investing similarly in increased display effort in order to attract females. PMID- 27680490 TI - A Simple, Non-Invasive Score to Predict Paroxysmal Atrial Fibrillation. AB - Paroxysmal atrial fibrillation (pAF) is a major risk factor for stroke but remains often unobserved. To predict the presence of pAF, we developed model scores based on echocardiographic and other clinical parameters from routine cardiac assessment. The scores can be easily implemented to clinical practice and might improve the early detection of pAF. In total, 47 echocardiographic and other clinical parameters were collected from 1000 patients with sinus rhythm (SR; n = 728), pAF (n = 161) and cAF (n = 111). We developed logistic models for classifying between pAF and SR that were reduced to the most predictive parameters. To facilitate clinical implementation, linear scores were derived. To study the pathophysiological progression to cAF, we analogously developed models for cAF prediction. For classification between pAF and SR, amongst 12 selected model parameters, the most predictive variables were tissue Doppler imaging velocity during atrial contraction (TDI, A'), left atrial diameter, age and aortic root diameter. Models for classifying between pAF and SR or between cAF and SR showed areas under the ROC curves of 0.80 or 0.93, which resembles classifiers with high discriminative power. The novel risk scores were suitable to predict the presence of pAF based on variables readily available from routine cardiac assessment. Modelling helped to quantitatively characterize the pathophysiologic transition from SR via pAF to cAF. Applying the scores may improve the early detection of pAF and might be used as decision aid for initiating preventive interventions to reduce AF-associated complications. PMID- 27680491 TI - Heterosexism, Depression, and Campus Engagement Among LGBTQ College Students: Intersectional Differences and Opportunities for Healing. AB - LGBTQ people experience health disparities related to multilevel processes of sexual and gender marginalization, and intersections with racism can compound these challenges for LGBTQ people of color. Although community engagement may be protective for mental health broadly and for LGBTQ communities in buffering against heterosexism, little research has been conducted on the racialized dynamics of these processes among LGBTQ communities. This study analyzes cross sectional survey data collected among a diverse sample of LGBTQ college students (n = 460), which was split by racial status. Linear regression models were used to test main effects of interpersonal heterosexism and engagement with campus organizations on depression, as well as moderating effects of campus engagement. For White LGBTQ students, engaging in student leadership appears to weaken the heterosexism-depression link-specifically, the experience of interpersonal microaggressions. For LGBTQ students of color, engaging in LGBTQ-specific spaces can strengthen the association between sexual orientation victimization and depression. PMID- 27680492 TI - Simulated microgravity enhances oligodendrocyte mitochondrial function and lipid metabolism. AB - The primary energy sources of mammalian cells are proteins, fats, and sugars that are processed by well-known biochemical mechanisms that have been discovered and studied in 1G (terrestrial gravity). Here we sought to determine how simulated microgravity (sim-uG) impacts both energy and lipid metabolism in oligodendrocytes (OLs), the myelin-forming cells in the central nervous system. We report increased mitochondrial respiration and increased glycolysis 24 hr after exposure to sim-uG. Moreover, examination of the secretome after 3 days' exposure of OLs to sim-uG increased the Krebs cycle (Krebs and Weitzman, ) flux in sim-uG. The secretome study also revealed a significant increase in the synthesis of fatty acids and complex lipids such as 1,2-dipalmitoyl-GPC (5.67); lysolipids like 1-oleoyl-GPE (4.48) were also increased by microgravity. Although longer-chain lipids were not observed in this study, it is possible that at longer time points OLs would have continued moving forward toward the synthesis of lipids that constitute myelin. For centuries, basic developmental biology research has been the pillar of an array of discoveries that have led to clinical applications; we believe that studies using microgravity will open new avenues to our understanding of the brain in health and disease-in particular, to the discovery of new molecules and mechanisms impossible to unveil while in 1G. (c) 2016 Wiley Periodicals, Inc. PMID- 27680493 TI - Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins. AB - Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N-O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N-O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins. PMID- 27680494 TI - Gaming for Safer Sex: Young German and Turkish People Report No Specific Culture Related Preferences Toward Educational Games Promoting Safer Sex. AB - OBJECTIVE: Comprehensive sex education programs specifically designed for adolescents and young adults that take into account gender norms and cultural background have shown promise as a means of countering the high sexually transmitted infection rate in young people. Recently, digital gaming interventions delivered on computers or mobile devices have emerged as another way to promote safer sex behavior in a young population. Tailoring these computer based interventions to their target population has been recognized to increase positive behavior outcomes. In this qualitative study, we investigated whether young female and male adults from two different cultural backgrounds (all living in Germany) would have different preferences and needs in relation to an educational game promoting safer sex. MATERIALS AND METHODS: We conducted four semistructured focus group interviews comprising open-ended questions with male and female participants who had either a German or a Turkish background. In total, 20 individuals, aged between 18 and 22 years, from two socially diverse and ethnically mixed vocational schools in Germany participated. RESULTS: Independent of cultural background and gender, participants preferred a real world design with a first-person visual perspective over a fantasy-like third person perspective. Furthermore, they preferred highly customizable avatars. All participants mentioned the importance of including an alcohol-intoxicated avatar and most participants wanted there to be additional information available about various safer sex approaches and about the use of different barrier protection methods. Males and females reported similar preferences for the design of an educational game promoting safer sex, with the only difference being exactly how the topic of having sexual intercourse should be addressed in the game. Males preferred a direct approach, whereas females had a preference for treating this subject more sympathetically. CONCLUSION: Educational games offer anonymity and can provide young people across different cultural backgrounds with gender tailored opportunities to experiment with specific safer sex precautions in a nonthreatening virtual environment, free from unwanted parental control and peer monitoring. PMID- 27680496 TI - Deficiency of histidine decarboxylase attenuates peripheral nerve fibre elongation into the epidermis in surfactant-treated mouse skin. PMID- 27680495 TI - Imprinting and flexibility in human face cognition. AB - Faces are an important cue to multiple physiological and psychological traits. Human preferences for exaggerated sex typicality (masculinity or femininity) in faces depend on multiple factors and show high inter-subject variability. To gain a deeper understanding of the mechanisms underlying facial femininity preferences in men, we tested the interactive effect of family structure (birth order, sibling sex-ratio and number of siblings) and parenthood status on these preferences. Based on a group of 1304 heterosexual men, we have found that preference for feminine faces was not only influenced by sibling age and sex, but also that fatherhood modulated this preference. Men with sisters had a weaker preference for femininity than men with brothers, highlighting a possible effect of a negative imprinting-like mechanism. What is more, fatherhood increased strongly the preference for facial femininity. Finally, for fathers with younger sisters only, the more the age difference increased between them, the more femininity preference increased. Overall our findings bring new insight into how early-acquired experience at the individual level may determine face preference in adulthood, and what is more, how these preferences are flexible and potentially dependent on parenthood status in adult men. PMID- 27680497 TI - Impact of co-pretreatment of calcium hydroxide and steam explosion on anaerobic digestion efficiency with corn stover. AB - Anaerobic digestion (AD) is an effective way to utilize the abundant resource of corn stover (CS). In this light, Ca(OH)2 pretreatment alone, steam explosion (SE) pretreatment alone, and co-pretreatment of Ca(OH)2 and SE were applied to improve the digestion efficiency of CS. Results showed that AD of co-pretreated CS with 1.0% Ca(OH)2 and SE at 1.5 MPa achieved the highest cumulative methane yield of [Formula: see text], which was 61.54% significantly higher (p < .01) than untreated CS. The biodegradability value of CS after co-pretreatment enhanced from 43.03% to 69.52%. Methane yield could be well fitted by the first-order model and the modified Gompertz model. In addition, composition and structural changes of CS after pretreatment were analyzed by a fiber analyzer, scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The validated results indicated that co-pretreatment of Ca(OH)2 and SE was efficient to improve the digestion performance of CS and might be a suitable method for agricultural waste pretreatment in the future AD industry. PMID- 27680498 TI - Observation on the ultrastructure morphology of HeLa cells treated with ethanol: Statistical analysis. AB - It is estimated that 5.9% of all human deaths are attributable to alcohol consumption and that the harmful use of ethanol ranks among the top five risk factors for causing disease, disability, and death worldwide. Ethanol is known to disrupt phospholipid packing and promote membrane hemifusion at lipid bilayers. With the exception of mitochondria involved in hormone synthesis, the sterol content of mitochondrial membranes is low. As membranes that are low in cholesterol have increased membrane fluidity and are the most easily disordered by ethanol, we hypothesize that mitochondria are sensitive targets for ethanol damage. HeLa cells were exposed to 50 mM ethanol and the direct effects of ethanol on cellular ultrastructure were examined utilizing transmission electron microscopy. Our ultramicroscopic analysis revealed that cells exposed to ethanol harbor fewer incidence of apoptotic morphology; however, significant alterations to mitochondria and to nuclei occurred. We observed statistical increases in the amount of irregular cells and cells with multiple nuclei, nuclei harboring indentations, and nuclei with multiple nucleolus-like bodies. Indeed, our analysis revealed that mitochondrial damage is the most extensive type of cellular damage. Rupturing of cristae was the most prominent damage followed by mitochondrial swelling. Ethanol exposure also resulted in increased amounts of mitochondrial rupturing, organelles with linked membranes, and mitochondria localizing to indentations of nuclear membranes. We theorize that these alterations could contribute to cellular defects in oxidative phosphorylation and, by extension, the inability to generate regular levels of cellular adenosine triphosphate. PMID- 27680499 TI - A paradox for air pollution controlling in China revealed by "APEC Blue" and "Parade Blue". AB - A series of strict emission control measures were implemented in Beijing and surrounding regions to ensure good air quality during the 2014 Asia-Pacific Economic Cooperation (APEC) summit and 2015 Grand Military Parade (Parade), which led to blue sky days during these two events commonly referred to as "APEC Blue" and "Parade Blue". Here we calculated Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) and Ozone Monitoring Instrument (OMI) NO2 and HCHO results based on well known DOAS trace gas fitting algorithm and WRF-Chem model (with measured climatology parameter and newest emission inventor) simulated trace gases profiles. We found the NO2 columns abruptly decreased both Parade (43%) and APEC (21%) compared with the periods before these two events. The back trajectory cluster analysis and the potential source contribution function (PSCF) proved regional transport from southern peripheral cities plays a key role in pollutants observed at Beijing. The diminishing transport contribution from southern air mass during Parade manifests the real effect of emission control measures on NO2 pollution. Based on the ratios of HCHO over NO2 we found there were not only limited the NO2 pollutant but also suppress the O3 contaminant during Parade, while O3 increased during the APEC. PMID- 27680500 TI - 'The greatest feeling you get, knowing you have made a big difference': survey findings on the motivation and experiences of trained volunteer doulas in England. AB - BACKGROUND: Support from a doula is known to have physical and emotional benefits for mothers, but there is little evidence about the experiences of volunteer doulas. This research aimed to understand the motivation and experiences of volunteer doulas who have been trained to support women during pregnancy, birth and the postnatal period. METHODS: A postal questionnaire survey was sent to volunteer doulas at five volunteer doula projects working in low-income areas in England. Quantitative and qualitative data were analysed in parallel using summary statistics and content analysis respectively. RESULTS: Eighty-nine volunteer doulas (response rate 34.5 %) from diverse backgrounds responded to the survey. Major motivators for volunteering included a desire to help others and, to a lesser extent, factors related to future employment. Most reported that the training was effective preparation for their role. They continued volunteering because they derived satisfaction from the doula role, and valued its social aspects. Their confidence, skills, employability and social connectedness had all increased, but many found the ending of the doula-mother relationship challenging. For a minority, negative aspects of their experience included time waiting to be allocated women to support and dissatisfaction with the way the doula service was run. DISCUSSION AND CONCLUSIONS: Most respondents found the experience rewarding. To maintain doulas' motivation as volunteers, services should: ensure doulas can start supporting women as soon as possible after completing the training; consider the merits of more flexible endings to the support relationship; offer opportunities for ongoing mutual support with other doulas, and ensure active support from service staff for volunteers. PMID- 27680501 TI - Targeted disruption of the mouse protein phosphatase ppm1l gene leads to structural abnormalities in the brain. AB - PPM1L, a member of the metal-dependent protein phosphatase (PPM) family, is involved in regulating the stress-activated protein kinase pathway and ceramide trafficking. However, the physiological function of PPM1L in the brain is unclear. In this study, we generated and analyzed ppm1l-deficient mice in order to investigate PPM1L functions in the brain. Our results indicate that ppm1l is highly expressed in the central nervous system during mouse development and that ppm1lDelta/Delta mice display impaired motor performance and morphological abnormalities in the forebrain. Electron microscopic and immunohistochemical analyses suggest that these abnormalities are due to impaired axonal tract formation. Our novel findings suggest an important role for PPM1L in brain development. PMID- 27680503 TI - Endpoints in strategies to reduce polypharmacy. PMID- 27680504 TI - Development of an opto-electronic fiber device with multiple nano-probes. AB - We present the fabrication and characterization of an opto-electronic fiber device which can allow for both electromechanical functionality and optical waveguiding capability. The air holes of a photonic crystal fiber are selectively sealed and then pumped with molten metal under pressure. The metal filled holes act as electrodes to which individual carbon nanotubes (CNT) are attached precisely by a laser-welding technique or a focused ion beam assisted pick-and bond technique. The optical modal profile and the group velocity dispersion of the fabricated device are studied both numerically and experimentally. We also present preliminary experimental proof showing the feasibility of electric actuation of a pair of nanotubes by applying up to 40 V potential difference between the filled electrodes. Furthermore, numerical simulations are carried out which agree with the experimentally observed displacement of the CNT upon electric actuation. The unique aspect of our device is that it provides optical waveguiding and electromechanical nano-probing capability in a single package. Such combined functionality can potentially enable simultaneous electrical and optical manipulation and interrogation at the nanoscale. PMID- 27680502 TI - Life-history studies by non-lethal sampling: using microchemical constituents of fin rays as chronological recorders. AB - Chemical properties of fin rays were investigated in nine fish species to test whether life-history characteristics can be analysed using a non-lethal and minimally invasive methodology. Fish specimens from public aquariums were acquired after fishes died in captivity. Analyses concentrated on exploring the differences between the wild and captive life periods of each fish, which were known from aquarium records. Differences between the two life periods were observed in both the trace-element and stable-isotope compositions of the chemical matrix of the fin ray. Trace-element concentrations in fin rays were compared with those in otoliths using measures of resolved variance and cross correlation to test the assumption of conserved matrices in the fin ray. Divalent ions and positively charged transition metals (i.e. Fe and Co) had strong associations between the two structures, suggesting conservation of material. Stable-isotope values of delta13 C and delta15 N differed between the wild and captive life periods in most of the fishes, also suggesting conserved matrices. delta13 C and delta15 N were derived from the organic matrix within the fin ray, which may present a stable-isotope chronology. Future studies can use these chronologies to study diet and movement trends on a temporal scale consistent with the entire lifetime of an individual. PMID- 27680506 TI - Influence of cerebral white matter hyperintensities on cognitive impairment in elderly medical patients. AB - AIM: We investigated the characteristics of elderly medical patients with white matter hyperintensities on magnetic resonance imaging. METHODS: A total of 213 patients (123 men and 90 women; mean age 74.8 years) reported their history of hypertension, diabetes, dyslipidemia, previous stroke, coronary heart disease and chronic kidney disease (CKD). All patients completed the Mini-Mental State Examination and Geriatric Depression Scale. White matter hyperintensities were evaluated for the periventricular region, basal ganglia (BGH), deep white matter and infratentorial region, and brain atrophy was calculated as bicaudate ratios. RESULTS: Patients with cognitive impairment (Mini-Mental State Examination score < 24) were significantly older (P = 0.001), had periventricular region hyperintensities (P = 0.029) and BGH (P = 0.0015), and showed atrophy (P < 0.0001). Logistic regression showed that cognitive impairment was predicted by stroke (OR 2.5, 95% CI 0.033-0.894, P = 0.036) and atrophy (OR 8.43, 95% CI 5.71 37.0, P = 0.0109). Multiple regressions showed that BGH was associated with CKD (beta = 0.213; P = 0.003), and infratentorial region was associated with stroke (beta = 0.157; P =0.035) and CKD (beta = 0.172; P = 0.016). Periventricular region was associated with age (beta = 0.2; P = 0.011) and Geriatric Depression Scale (beta = 0.151; P = 0.037), and deep white matter hyperintensities with age (beta = 0.189; P = 0.016). CONCLUSIONS: Although cognitive impairment in elderly medical patients is associated with stroke and brain atrophy, white matter hyperintensities, especially BGH and infratentorial region, are associated with cognitive decline in relation to CKD. Geriatr Gerontol Int 2017; 17: 1488-1493. PMID- 27680505 TI - The possible roles of B-cell novel protein-1 (BCNP1) in cellular signalling pathways and in cancer. AB - B-cell novel protein-1 (BCNP1) or Family member of 129C (FAM129C) was identified as a B-cell-specific plasma-membrane protein. Bioinformatics analysis predicted that BCNP1 might be heavily phosphorylated. The BCNP1 protein contains a pleckstrin homology (PH) domain, two proline-rich (PR) regions and a Leucine Zipper (LZ) domain suggesting that it may be involved in protein-protein interactions. Using The Cancer Genome Atlas (TCGA) data sets, we investigated the correlation of alteration of the BCNP1 copy-number changes and mutations in several cancer types. We also investigated the function of BCNP1 in cellular signalling pathways. We found that BCNP1 is highly altered in some types of cancers and that BCNP1 copy-number changes and mutations co-occur with other molecular alteration events for TP53 (tumour protein P53), PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha), MAPK1 (mitogen-activated protein kinase-1; ERK: extracellular signal regulated kinase), KRAS (Kirsten rat sarcoma viral oncogene homolog) and AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2). We also found that PI3K (Phoshoinositide 3-kinase) inhibition and p38 MAPK (p38 mitogen-activated protein kinase) activation leads to reduction in phosphorylation of BCNP1 at serine residues, suggesting that BCNP1 phosphorylation is PI3K and p38MAPK dependent and that it might be involved in cancer. Its degradation depends on a proteasome-mediated pathway. PMID- 27680508 TI - Micro-CT Evaluation of Ceramic Inlays: Comparison of the Marginal and Internal Fit of Five and Three Axis CAM Systems with a Heat Press Technique. AB - OBJECTIVES: To evaluate the marginal and internal adaptation of CAD/CAM lithium disilicate inlay restorations fabricated by two milling systems (Five and Three axis), and a traditional heat-press technique. METHODS: Fifteen premolar teeth with an MOD cavity preparation were fabricated. Lithium-disilicate inlay restorations were obtained by three fabrication techniques and fitted to their dies (n = 15/gp) as follows: Group-1, three-axis milling system, Group-2, five axis milling system, Group-3, conventional heat-press technique. Gaps were evaluated by X-ray microtomography. Marginal gap (MG), occlusal-marginal gap (OMG), proximal-marginal gap (PMG), gingival-marginal gap (GMG), absolute marginal discrepancy (AMD), axial-internal gap (AIG), and occlusal-internal gap (OIG) were evaluated at 120 different points per inlay. Data were analyzed using repeated measures ANOVA. Pairwise comparisons were conducted for post-hoc testes and the Bonferroni correction was used to adjust for multiple comparisons (alpha = 0.007). RESULTS: The heat-press group demonstrated significantly smaller mean values amongst all outcomes compared with CAD/CAM groups except for GMG, where there was no statistically significant difference between groups in the ANOVA (p = 0.042). Within the CAD/CAM groups, the five-axis group showed significantly lower OMG mean-value compared with the three-axis group p < 0.001, and lower AIG mean-value compared with the three-axis group p < 0.001. There was no significant difference between the five-axis and the three-axis groups' AMD, MG, PMG, and OIG locations. CONCLUSION: Different fabrication techniques affected the marginal and internal adaptation of ceramic inlay restorations. The heat-press group showed the best marginal and internal adaptation results; however, in every group, all samples were within the clinically acceptable MG limit (100 MUm). CLINICAL SIGNIFICANCE: The marginal fit and internal adaptation of inlay ceramic restorations fabricated by a five-axis milling system have not been tested or compared with those fabricated by three-axis machines and the conventional heat press method. The preferred method of inlay fabrication, whether in the lab or chair side, may be influenced by the results of this study and could affect future clinical decision-making. (J Esthet Restor Dent 29:49-58, 2017). PMID- 27680507 TI - Mutation in SSUH2 Causes Autosomal-Dominant Dentin Dysplasia Type I. AB - Dentin dysplasia type I (DDI) is an autosomal-dominant genetic disorder resulting from dentin defects. The molecular basis of DDI remains unclear. DDI exhibits unique characteristics with phenotypes featuring obliteration of pulp chambers and diminutive root, thus providing a useful model for understanding the genetics of tooth formation. Using a large Chinese family with 14 DDI patients, we mapped the gene locus responsible for DDI to 3p26.1-3p24.3 and further identified a missense mutation, c.353C>A (p.P118Q) in the SSUH2 gene on 3p26.1, which co segregated with DDI. We showed that SSUH2 (p.P118Q) perturbed the structure and significantly reduced levels of mutant (MT) protein and mRNA compared with wild type SSUH2. Furthermore, MT P141Q knock-in mice (+/- and -/-) had a unique partial obliteration of the pulp cavity and upregulation or downregulation of six major genes involved in odontogenesis: Dspp, Dmp1, Runx2, Pax9, Bmp2, and Dlx2. The phenotype of missing teeth was determined in zebrafish with morpholino gene knockdowns and rescued by injection of normal human mRNA. Taken together, our observations demonstrate that SSUH2 disrupts dental formation and that this novel gene, together with other odontogenesis genes, is involved in tooth development. PMID- 27680509 TI - Preserving enzymatic activity and enhancing biochemical stability of glutathione transferase by soluble additives under free and tethered conditions. AB - In the present study, we report the effect of four different soluble additives (sucrose, lactitol, superfloc c577, and dextran sulfate) on the stability of glutathione transferase 1 enzyme from Zea mays (ZmGSTF1-1) under free and tethered conditions at 4 and 25 degrees C. Among all additives, the best stabilizing effects were observed in the case of superfloc c577 and sucrose at both tested temperatures, yet at distinct concentrations at each condition. Those two stabilizing agents were further combined and potential positive synergistic effects were investigated. In addition, we assessed the long-term storage and operational stability of ZmGSTF1-1 under tethered conditions in the presence of additives, which provided the most conducive effects on its stability under free conditions. Our results strongly suggest that the presence of additives may be beneficial to the stability of the enzyme under both free and tethered conditions. Thermodynamic analysis of the free enzyme in the presence of sucrose, which exhibited the best stabilizing effect at both temperatures, shed light on the possible mechanism of action. Given the considerable importance of the development of GST-based biosensors with prolonged stability, the present work may be of general interest to researchers in the field of applied enzymology. PMID- 27680510 TI - Metabolic syndrome increases cardiovascular events but not hepatic events and death in patients with chronic hepatitis B. AB - : Metabolic syndrome is an independent risk factor of liver cirrhosis in chronic hepatitis B (CHB). Whether metabolic syndrome affects the long-term prognosis of CHB patients in terms of hepatic events, cardiovascular events, and death remains unknown. We aimed to determine the incidences of hepatic events, cardiovascular events, and death in CHB patients with or without metabolic syndrome. From 2006 to 2008, we prospectively recruited 1,466 CHB patients for liver stiffness measurement (LSM) with transient elastography together with detailed metabolic profiling as baseline assessment. Patients were prospectively followed for any clinical events. The impact of LSM and metabolic syndrome on hepatic events, cardiovascular events, and death was evaluated. At baseline visit, the mean age was 46 +/- 12 years, LSM value was 8.4 +/- 6.3 kPa, and 188 patients (12.8%) had metabolic syndrome. At a mean follow-up of 88 +/- 20 months, 93 and 44 patients developed hepatic and cardiovascular events, respectively; 70 patients died. Patients with baseline LSM >8.0 kPa had higher cumulative probability of hepatic events than those with LSM <=8.0kPa at 8 years (12.3% versus 3.1%, P < 0.001). Patients with metabolic syndrome had higher cumulative probability of cardiovascular events than those without (8.0% versus 2.1%, P < 0.001). High LSM had no impact on cardiovascular events; neither did metabolic syndrome on hepatic events. LSM >8.0 kPa but not metabolic syndrome was an independent risk factor of death, with adjusted hazard ratios of 1.9 (95% confidence interval 1.1-3.2, P = 0.023) and 1.3 (95% confidence interval 0.8-2.4, P = 0.310), respectively. CONCLUSIONS: Metabolic syndrome increased the risk of cardiovascular events but not hepatic events and death; LSM was the important risk factor of hepatic events and death in CHB patients. (Hepatology 2016;64:1507-1517). PMID- 27680511 TI - Managing patients with delusional infestations in an integrated psychodermatology clinic is much more cost-effective than a general dermatology or primary care setting. PMID- 27680512 TI - Integrative transcriptomic meta-analysis of Parkinson's disease and depression identifies NAMPT as a potential blood biomarker for de novo Parkinson's disease. AB - Emerging research indicates that depression could be one of the earliest prodromal symptoms or risk factors associated with the pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, but the mechanisms underlying the association between both diseases remains unknown. Understanding the molecular networks linking these diseases could facilitate the discovery of novel diagnostic and therapeutics. Transcriptomic meta-analysis and network analysis of blood microarrays from untreated patients with PD and depression identified genes enriched in pathways related to the immune system, metabolism of lipids, glucose, fatty acids, nicotinamide, lysosome, insulin signaling and type 1 diabetes. Nicotinamide phosphoribosyltransferase (NAMPT), an adipokine that plays a role in lipid and glucose metabolism, was identified as the most significant dysregulated gene. Relative abundance of NAMPT was upregulated in blood of 99 early stage and drug naive PD patients compared to 101 healthy controls (HC) nested in the cross sectional Parkinson's Progression Markers Initiative (PPMI). Thus, here we demonstrate that shared molecular networks between PD and depression provide an additional source of biologically relevant biomarkers. Evaluation of NAMPT in a larger prospective longitudinal study including samples from other neurodegenerative diseases, and patients at risk of PD is warranted. PMID- 27680514 TI - Mutational profiling of a MonoMAC syndrome family with GATA2 deficiency. PMID- 27680513 TI - Simulation study of the ability of a computationally-designed peptide to recognize target tRNALys3 and other decoy tRNAs. AB - In this paper, we investigate the ability of our computationally-designed peptide, Pept10 (PNWNGNRWLNNCLRG), to recognize the anticodon stem and loop (ASL) domain of the hypermodified tRNALys3 (mcm5 s2 U34 ,ms2 t6 A37 ), a reverse transcription primer of HIV replication. Five other ASLs, the singly modified ASLLys3 (ms2 t6 A37 ), ASLLys3 (s2 U34 ), ASLLys3 (Psi39 ), ASLLys1,2 (t6 A37 ), and ASLGlu (s2 U34 ), were used as decoys. Explicit-solvent atomistic molecular dynamics simulations were performed to examine the process of binding of Pept10 with the target ASLLys3 (mcm5 s2 U34 ,ms2 t6 A37 ) and the decoy ASLs. Simulation results demonstrated that Pept10 is capable of recognizing the target ASLLys3 (mcm5 s2 U34 ,ms2 t6 A37 ) as well as one of the decoys, ASLLys3 (Psi39 ), but screens out the other four decoy ASLs. The interchain van der Waals (VDW) and charge-charge (ELE + EGB) energies for the two best complexes were evaluated to shed light on the molecular recognition mechanism between Pept10 and ASLs. The results indicated that Pept10 recognizes and binds to the target ASLLys3 (mcm5 s2 U34 ,ms2 t6 A37 ) through residues W3 and R7 which interact with the nucleotides mcm5 s2 U34 , U35 , and ms2 t6 A37 via the interchain VDW energy. Pept10 also recognizes the decoy ASLLys3 (Psi39 ) through residue R14 which contacts the nucleotide U36 via the interchain VDW energy. Regardless of the type of ASL, the positively charged arginines on Pept10 are attracted to the negatively charged phosphate linkages on the ASL via the interchain ELE + EGB energy, thereby enhancing the binding affinity. PMID- 27680515 TI - The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. AB - Alterations in TP53 have been described in many cancer types including hematological neoplasms. We aimed at comparing TP53 mutations (mut) and deletions (del) in a large cohort of patients with hematological malignancies (n=3307), including AML (n=858), MDS (n=943), ALL (n=358), CLL (n=1148). Overall, alterations in TP53 were detected in 332/3307 cases (10%). The highest frequency was observed in ALL (total: 19%; mut+del: 6%; mut only: 8%; del only: 5%) and AML (total: 13%; mut+del: 5%; mut only: 7%; del only: 1%), whereas TP53 alterations occurred less frequently in CLL (total: 8%) and MDS (total: 7%). TP53 mutations were significantly more frequent in patients ?60 vs <60 years in AML (9% vs 2%, P<0.001) and ALL (12% vs 6%, P<0.001). TP53mut+del had a significant negative impact on overall survival in all entities, whereas differences were observed regarding TP53mut only or TP53del only: TP53mut only impacted survival in AML (36 vs 9 months, P<0.001) and MDS (65 vs 19 months, P<0.001), TP53del only in CLL (not reached vs 64 months, P=0.008) and MDS (65 vs 24 months, P=0.011). As substantial differences between the entities are observed regarding correlation to age and survival, we suggest evaluation of both TP53 deletion and mutation status. PMID- 27680517 TI - Modern Implants: Surgical and Injectable. PMID- 27680518 TI - Filling the Midface: Injectables. AB - Volumizing the face has become commonplace on the facial aesthetic scene, with a rapid explosion of popularity in the field of nonsurgical rejuvenation. Three dimensional enhancement of the midface with fillers provides the surgeon with a minimal downtime opportunity to treat early aging or reverse nonsurgical volume loss. With new products come advancements in techniques and the understanding of reversal of the effects of aging. While providing minimal downtime and risk, complications can occur and the physician must be able to recognize and treat these issues. It is crucial for the injector to understand and process these factors to ensure patient satisfaction and safety. PMID- 27680519 TI - Solid Midfacial Implants: When Fillers Are Not Enough. AB - The aging process results in volumetric changes on multiple levels of the face including the skin, soft tissue, and underlying facial skeleton. Malar and mandibular augmentation with facial fillers and alloplastic implants are two treatment options used to achieve the goal of volume enhancement. Noninvasive modalities have become increasingly popular due to the availability of office based options that require a limited understanding of facial aesthetics, a basic grasp of the mechanisms behind the aging process, and no level of surgical expertise or training. It is important, however, to understand the limitations and appropriate use of each technique, surgical and nonsurgical, either as a sole modality or in conjunction with each other to attain optimal aesthetic results. Although minimally invasive soft-tissue augmentation procedures such as fillers offer midface treatment options, alloplastic implants provide a stable support platform or scaffolding for skeletal and soft-tissue augmentation that fillers alone cannot often provide. A multilevel understanding of facial aesthetics must include the facial skeletal architecture and foundation that it provides for proper soft-tissue draping and contour. Alloplastic implants remain the standard for skeletal augmentation and remain the mainstay when fillers are not sufficient for midface augmentation. PMID- 27680516 TI - Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation. AB - BACKGROUND AND PURPOSE: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. METHODS: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. RESULTS: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype-genotype correlations. CONCLUSIONS: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex. PMID- 27680520 TI - Surgical Nasal Implants: Indications and Risks. AB - Rhinoplasty often requires the use of grafting material, and the goal of the specific graft dictates the ideal characteristics of the material to be used. An ideal material would be biologically inert, resistant to infection, noncarcinogenic, nondegradable, widely available, cost-effective, readily modifiable, and easily removable, have compatible biomechanical characteristics, retain physical properties over time, and not migrate. Unfortunately, no material currently in existence meets all of these criteria. In modern rhinoplasty, autologous grafts are the gold standard against which all other nasal implants are measured and offer the safest long-term results for most patients. They are easily manipulated, have inherent stability and biomechanical characteristics similar to the native nasal framework, and confer minimal risk of complications. Modern homologous and alloplastic materials have gained considerable support in recent years because they are readily available in endless quantity, do not require a second surgical site for harvest, and are generally considered safe if most circumstances, but they confer additional risk and have biomechanical characteristics different from that of the native nasal framework. To address some of these issues, we provide a contemporary review of autologous, homologous, and alloplastic materials commonly used in rhinoplasty surgery. PMID- 27680521 TI - Nonsurgical Rhinoplasty. AB - "Nonsurgical rhinoplasty" refers to the use of injectable temporary fillers used to augment select areas of the nose to achieve improved appearance or function in select patients. Nonpermanent fillers can be used safely and must be properly chosen based on their properties and the desired effect. In addition to proper patient and product selection, a thorough understanding of nasal anatomy, analysis of the deformity, and recommended injection techniques are absolutely necessary to obtain good outcomes and avoid complications. The proper plane for injection is the deep fatty layer, just superficial to the perichondrium and periosteum. Erring on the side of undercorrection, small incremental boluses, and constant reassessment are the best way to avoid overfilling or producing irregularities and asymmetries. The most devastating and feared complications are vascular compromise, tissue necrosis, and even blindness, making the nose a challenging area to treat with fillers. The surgeon wishing to use fillers in the nose should be familiar with proper technique, recognition of developing problems, and have a practical plan in place for immediate reversal and treatment. PMID- 27680522 TI - Choosing the Best Procedure to Augment the Chin: Is Anything Better than an Implant? AB - The chin plays a very important role in overall facial appearance, and aesthetic procedures to augment the chin in patients with microgenia can improve overall facial balance. Many procedures exist to enhance the appearance of a small chin. Procedures include surgeries such as placement of an alloplast implant and bony osteotomy of the mentum (sliding genioplasty). The advantages and disadvantages of each surgical technique are well documented. Although surgical augmentation of the chin has been the gold standard of therapy, recent development of injectable filler products with lifting capacity has changed the way that many practitioners alter chin shape and size. Filler agents allow augmentation of the chin in horizontal (projection), vertical, and transverse dimensions. Injectable fillers are a simple, noninvasive procedure that causes minimal to no downtime, incurs minimal risks, and allows the practitioner to shape the chin in three dimensions. This procedure allows patients to enhance their chin size without requiring an operative visit. As more and varied filler products become FDA-approved, the versatility and application of these agents will increase. PMID- 27680523 TI - Augmenting the Prejowl: Deciding between Fat, Fillers, and Implants. AB - The prejowl sulcus is a complex anatomic structure that results from several age related changes in the lower face. These changes include the localized atrophy of a segment of the mandible inferior to the mental foreman, fat atrophy, and dehiscence and laxity of the ligamentous and muscular components of the region. The correction of the prejowl sulcus is rarely accomplished through rhytidectomy alone. Instead, the volume deficit of the sulcus usually requires the replacement of volume. Solid implants, fillers, and fat transfer may be used to improve the contour of the lower face. These can be used in isolation and in conjunction with rhytidectomy. The decision of what method to be used depends on the severity of the deformity, the patient's adjacent anatomy, the patient's wishes, and the skill set of the surgeon. PMID- 27680524 TI - Solid Implants in Facial Plastic Surgery: Potential Complications and How to Prevent Them. AB - Allogenic implants are an effective alternative to autologous grafts in the reconstruction of facial defects. These implants are used to reconstruct a variety of bony and soft-tissue defects, including the frontal and temporal regions; internal orbit; infraorbital rim; malar, paranasal, and nasal regions; mandible; and chin. In comparison to their autologous counterparts, alloplastic materials are more readily available, lack donor-site morbidity, decrease surgical time and cost, and still have relatively good postoperative tissue tolerance. However, these implants are not without their own spectrum of complications. Common solid implant materials include silicone, GoreTex (expanded polytetrafluorethylene; W. L. Gore & Associates Inc., Flagstaff, AZ), MedPor (high-density porous polyethylene; Porex Industries, Fairburn, GA), and Mersilene mesh (nonresorbable polyester fiber; Ethicon, Somerville, NJ). Each of these materials poses certain complication risks based on their surface contour (smooth vs. porous), pliability, and reactivity with surrounding tissue. In addition, certain implant locations within the head and neck are at risk for different postoperative complications. Although there are no evidence-based guidelines for implant reconstruction to help avoid common complications, there are several principles and techniques that are commonly employed by surgeons to help reduce complication rates. These include careful patient selection, proper choice of operative procedure, infection control practices (including pre/intraoperative systemic antibiotics, meticulous aseptic technique, impregnation/soaking of implant in antibiotic, irrigation of implant pocket with antibiotic, careful closure of tissue layers, and postoperative oral antibiotics), preoperative implant shaping, choice of surgical approach, and intraoperative surgical techniques. Larger, controlled trials are needed to confirm the efficacy of the aforementioned techniques in the reduction of postoperative complications. PMID- 27680526 TI - The Downside of Fat: Avoiding and Treating Complications. AB - Three-dimensional facial volume restoration using fat has become widely accepted as an essential component of facial rejuvenation. Transplanted fat has benefits due to its inherently nonallergenic nature. The versatility of fat grafts allows for their use in all types of facial enhancement-improving the appearance of nasolabial folds, mesolabial grooves, flattened cheeks and upper lips, glabellar furrows, lipoatrophy, acne scars, and temporal hollowing. Yet despite its virtues as the ideal filler, autologous fat has its shortcomings with risks of complications. Our objective in this article is to present a systematic approach demonstrating the complications that can occur with each step of autologous fat grafting in facial rejuvenation and offering pearls to avoid and treat these complications. PMID- 27680527 TI - Facelift Techniques That Restore Facial Volume. AB - The aging face results in increase in laxity of the skin and the underlying supporting tissue. There is a fundamental volume loss in the face and it is most apparent in the midface. A traditional superficial musculoaponeurotic system (SMAS) rhytidectomy addresses the laxity of the face but not volume loss. Multivector high SMAS plication allows for natural excess tissue to be placed into the area of volume loss, thereby addressing midface volume loss. This technique is easy to perform, reproducible, and effective with the added benefit of helping to volumize the lower face. PMID- 27680525 TI - Adverse Reactions to Injectable Fillers. AB - As the use of fillers becomes increasingly more common and the skill level of those injecting is so varied, adverse events can be expected to increase as well. Avoiding complications is always the best measure, and with appropriate training and injection techniques, many complications can be avoided. However, adverse events can occur in the best of hands, and early detection and treatment may eliminate or minimize sequelae. This article is an effort to help in that endeavor. PMID- 27680528 TI - Tissue Engineering and the Future of Facial Volumization. AB - Volume loss due to facial aging can be restored by facial volumization using a variety of materials. Volumization can be performed in isolation or concurrent with other facial rejuvenation procedures to obtain an optimal aesthetic result. There is a myriad of manufactured products available for volumization. The use of autologous fat as facial filler has been adopted more recently and possesses certain advantages; however, the ideal filler is still lacking. Tissue engineering may offer a solution. This technology would provide autologous soft tissue components for use in facial volumization. The use of stem cells may enable customization of the engineered product for the specific needs of each patient. PMID- 27680529 TI - Modified Endonasal Tongue-in-Groove Technique. AB - Achieving stable and desirable changes in tip rotation (TR) and tip projection (TP) is among the primary goals of modern day rhinoplasty. The tongue-in-groove (TIG) technique is one technique in rhinoplasty used to improve TR and/or TP. Performing TIG endonasally using a permanent suture can be quite cumbersome as the suture needs to be buried under the skin. We describe a variation of TIG technique for endonasal rhinoplasty using a permanent suture buried in small columellar skin incisions. The technique details are described and the postoperative changes in TR and TP are analyzed for the degree of change and longevity. A retrospective review of the preoperative and postoperative photographs of 12 patients treated with the endonasal TIG technique were analyzed for changes in TR and TP. Out of 12 patients, there were seven females (58.3%) and five males (41.7%), with age ranging from 17 to 49 years. The follow-up ranged from 6 months to 53 months, with mean follow-up of 12.1 months. All patients were treated by the senior author in a major New York City hospital. Postoperative changes in TR and TP were compared by measuring the nasolabial angle as well as the Goode ratio using a photo editing software. Using a t-test and a p-value criteria of 0.05, the difference between the preoperative and postoperative TR (p = 0.0069) and TP (p = 0.026) was found to be statistically significant. None of the study patients developed any complications related to the use of a permanent suture material during the follow-up period. Our modified TIG technique is a quick, reliable, and safe option in the surgical armamentarium to achieve desired changes in TR and/or TP. LEVEL OF EVIDENCE: 4. PMID- 27680531 TI - Lasers and Light, Peels and Abrasions. PMID- 27680532 TI - Maintenance lenalidomide after transplantation: How much is enough? PMID- 27680530 TI - A Case of Basaloid Degeneration of Nevus Sebaceous during Childhood: Should Nevus Sebaceous Be Excised or Followed Up? PMID- 27680534 TI - Comparative Toxicity and Metabolism of N-Acyl Homologues of Acetaminophen and Its Isomer 3'-Hydroxyacetanilide. AB - The hepatotoxicity of acetaminophen (APAP) is generally attributed to the formation of a reactive quinoneimine metabolite (NAPQI) that depletes glutathione and covalently binds to hepatocellular proteins. To explore the importance of the N-acyl group in APAP metabolism and toxicity, we synthesized 12 acyl side chain homologues of acetaminophen (APAP) and its 3'-regioisomer (AMAP), including the respective N-(4-pentynoyl) analogues PYPAP and PYMAP. Rat hepatocytes converted APAP, AMAP, PYPAP, and PYMAP extensively to O-glucuronide and O-sulfate conjugates in varying proportions, whereas glutathione or cysteine conjugates were observed only for APAP and PYPAP. PYPAP and PYMAP also underwent N deacylation followed by O-sulfation and/or N-acetylation to a modest extent. The overall rates of metabolism in hepatocytes varied approximately 2-fold in the order APAP < AMAP ~ PYPAP < PYMAP. Rat liver microsomes supplemented with NADPH and GSH converted APAP and PYPAP to their respective glutathione conjugates (formed via a reactive quinoneimine intermediate). With PYPAP only, a hydroxylated GSH conjugate was also observed. Thus, differences in biotransformation among these analogues were modest and mostly quantitative in nature. Cytotoxicity was evaluated in cultured hepatocytes by monitoring cell death using time-lapse photomicrography coupled with Hoechst 33342 and CellTox Green dyes to facilitate counting live cells vs dead cells, respectively. Progress curves for cell death and the areas under those curves showed that toxicity was markedly dependent on compound, concentration, and time. AMAP was essentially equipotent with APAP. Homologating the acyl side chain from C-2 to C 5 led to progressive increases in toxicity up to 80-fold in the para series. In conclusion, whereas N- or ring-substitution on APAP decrease metabolism and toxicity, homologating the N-acyl side chain increases metabolism about 2-fold, preserves the chemical reactivity of quinoneimine metabolites, and increases toxicity by up to 80-fold. PMID- 27680533 TI - A potent and selective small molecule inhibitor of sirtuin 1 promotes differentiation of pluripotent P19 cells into functional neurons. AB - Sirtuin 1 (SIRT1) is known to suppress differentiation of pluripotent/multipotent cells and neural progenitor cells into neurons by blocking activation of transcription factors critical for neurogenesis. EX-527 is a highly selective and potent inhibitor against SIRT1 and has been used as a chemical probe that modulates SIRT1-associated biological processes. However, the effect of EX-527 on neuronal differentiation in pluripotent cells has not been well elucidated. Here, we report an examination of EX-527 effects on neurogenesis of pluripotent P19 cells. The results showed that EX-527 greatly accelerated differentiation of P19 cells into neurons without generation of cardiac cells and astrocytes. Importantly, neurons derived from P19 cells treated with EX-527 generated voltage dependent sodium currents and depolarization-induced action potentials. The findings indicate that the differentiated cells have electrophysiological properties. The present study suggests that the selective SIRT1 inhibitor could have the potential of being employed as a chemical inducer to generate functionally active neurons. PMID- 27680535 TI - Safety and pain in electrodiagnostic studies. AB - Discomfort is an unavoidable part of electrodiagnostic (EDX) studies. The most readily modifiable mediator of electromyography (EMG)-associated pain is muscle selection. Interventions that may reduce pain include vapocoolant spray, ibuprofen, and techniques such as slapping or stretching the skin. Needlestick injuries to health care workers carry the risk of transmitting bloodborne illnesses, but other infectious complications of EDX studies are very rare. EMG probably contributes to asymptomatic hemorrhage in approximately 1% of patients, but clinically significant bleeding has only been reported a few times. Therapeutic anticoagulation does not significantly increase this risk. With standard procedures, there have been no reports of patients developing cardiac arrhythmia from nerve conduction studies. No special precautions are necessary in patients with implantable cardiac devices or intravenous lines. There is a small risk of pneumothorax associated with EMG of the diaphragm and chest wall muscles. Several techniques have been suggested to improve the safety of diaphragm EMG. Muscle Nerve 55: 149-159, 2017. PMID- 27680537 TI - On the Functionality of Complex Intermetallics: Frustration, Chemical Pressure Relief, and Potential Rattling Atoms in Y11Ni60C6. AB - Intermetallic carbides provide excellent model systems for exploring how frustration can shape the structures and properties of inorganic materials. Combinations of several metals with carbon can be designed in which the formation of tetrahedrally close-packed (TCP) intermetallics conflicts with the C atoms' requirement of trigonal prismatic or octahedral coordination environments, as offered by the simple close-packings (SCP) of equally sized spheres. In this Article, we explore the driving forces that lead to the coexistence of these incompatible arrangements in the Yb11Ni60C6-type compound Y11Ni60C6 (cI154), as well as potential consequences of this intergrowth for the phase's physical properties. Our focus begins on the structure's SCP regions, which appear as C stuffed versions of a AuCu3-type YNi3 phase that is not observed on its own in the Y-Ni system. DFT-Chemical Pressure (DFT-CP) calculations on this hypothetical YNi3 phase reveal large negative pressures within the Ni sublattice, as it is stretched to accommodate the size requirements of the Y atoms. In the Y11Ni60C6 structure, two structural mechanisms for addressing these CP issues appear: the incorporation of interstitial C atoms, and the presence of interfaces with CaCu5 type domains. The relative roles of these two mechanisms are investigated with the CP analysis on a hypothetical YNi3Cx series of C-stuffed AuCu3-type phases, the Y-Ni sublattice of Y11Ni60C6, and finally the full Y11Ni60C6 structure. Through these calculations, the C atoms appear to play the roles of relieving positive Y CPs and supporting relaxation at the AuCu3-type/CaCu5-type interfaces, where the cancellation occurs between opposite CPs experienced by the Y atoms in the two parent structures (following the epitaxial stabilization mechanism). The CP analysis of Y11Ni60C6 also highlights a sublattice of Y and Ni atoms with large negative CPs (and thus the potential for soft vibrational modes), illustrating how frustrated structures could lead to the full realization of the phonon glass-electron crystal concept. PMID- 27680536 TI - CT Reporting of Pediatric Neck Infections and Masses: Don't Forget the Veins. PMID- 27680538 TI - Engineering of a microbial coculture of Escherichia coli strains for the biosynthesis of resveratrol. AB - BACKGROUND: Resveratrol is a plant natural product with many health-protecting effects which makes it an attractive chemical both for academic studies and industrial purposes. However, the low quantities naturally produced by plants as well as the unsustainable procedures of extraction, purification and concentration have prompted many biotechnological approaches to produce this chemical in large quantities from renewable sources. None of these approaches have considered a microbial coculture strategy to produce this compound. The aim of this study was to prove the functionality of a microbial coculture for the biosynthesis of resveratrol. RESULTS: In this work, we have successfully applied a coculture system strategy comprised of two populations of Escherichia coli strains, each with a partial and complementary section of the pathway leading to the biosynthesis of the stilbene resveratrol. The first strain is a pheA knockout mutant previously engineered to excrete p-coumaric acid into the medium through the overexpression of genes encoding a tyrosine ammonia lyase from Rhodothorula glutinis, a feedback resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase and a transketolase. The second strain in the coculture was engineered to express the second part of the resveratrol biosynthetic pathway through the introduction of synthetic genes encoding the 4-coumaroyl-CoA ligase from Streptomyces coelicolor A2 and the stilbene synthase either from the peanut Arachis hypogaea or the grapevine Vitis vinifera, the latter synthesized employing a gene harmonization strategy and showing better resveratrol production performance. Batch cultures were performed in mineral medium with glycerol as the sole carbon source, where a final titer of 22.6 mg/L of resveratrol was produced in 30 h. CONCLUSIONS: To our knowledge, this is the first time that a coculture of bacterial strains is used for the biosynthesis of resveratrol from glycerol, having the potential for a greater improvement in the product yield and avoiding the use of precursors such as p-coumaric acid, yeast extract or an expensive inhibitor such as cerulenin. PMID- 27680539 TI - Inflammatory biomarkers, disease activity index, and self-reported disability may be predictors of chronic arthritis after chikungunya infection: brief report. AB - The chikungunya virus (ChikV) is a reemerging mosquito-borne pathogen that causes disabling chronic arthritis. The relationship between clinical evolution and inflammatory biomarkers in patients with ChikV-induced arthritis has not been fully described. We performed a prospective case series to evaluate the association among joint involvement, self-reported disability, and inflammatory biomarkers. Patients with ChikV infection were followed for 1 year. Joint involvement and self-reported disability were evaluated with disease activity index 28 (DAS-28) and World Health Organization Disablement Assessment Schedule II (WHODAS-II). Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were used as biomarkers. Ten patients with mean age 48 +/-15.04 years were included. Symptoms at diagnosis were fever, arthralgias, myalgias, rash, arthritis, nausea, vomiting, and back pain. Polyarticular involvement was present in seven cases. At diagnosis, measures were as follows: DAS-28, 5.08+/-1.11; WHODAS-II score, 72.3+/-10.3 %; CRP, 5.09+/-7.23 mg/dL; ESR, 33.5+/-17.5 mm/h; RF, 64+/-21.7 IU/mL; and IL-6, 17.6+/-10.3 pg/mL. Six patients developed subacute and chronic symptoms. During follow-up, DAS-28 index, WHODAS-II score, ESR, and IL-6 were statistically different in patients with subacute and chronic symptoms compared to those who resolved in the acute phase (p < 0.05). DAS-28 index, WHODAS-II score, and IL-6 were related to chronicity of articular symptoms and could be used as predictors of ChikV-induced arthritis. PMID- 27680540 TI - Rheumatologists' adherence to a disease activity score steered treatment protocol in early arthritis patients is less if the target is remission. AB - To compare rheumatologists' adherence to treatment protocols for rheumatoid arthritis (RA) targeted at Disease Activity Score (DAS) <=2.4 or <1.6. The BeSt study enrolled 508 early RA (1987) patients targeted at DAS <=2.4. The IMPROVED study included 479 early RA (2010) and 122 undifferentiated arthritis patients targeted at DAS <1.6. We evaluated rheumatologists' adherence to the protocols and assessed associated opinions and conditions during 5 years. Protocol adherence was higher in BeSt than in IMPROVED (86 and 70 %), with a greater decrease in IMPROVED (from 100 to 48 %) than in BeSt (100 to 72 %). In BeSt, 50 % of non-adherence was against treatment intensification/restart, compared to 63 % in IMPROVED and 50 vs. 37 % were against tapering/discontinuation. In both studies, non-adherence was associated with physicians' disagreement with DAS or with next treatment step and if patient's visual analogue scale (VAS) for general health was >=20 mm higher than the physician's VAS. In IMPROVED, also discrepancies between swelling, pain, erythrocyte sedimentation rate, and VASgh were associated with non-adherence. Adherence to DAS steered treatment protocols was high but decreased over 5 years, more in a DAS <1.6 steered protocol. Non adherence was more likely if physicians disagreed with DAS or next treatment step. In the DAS <1.6 steered protocol, non-adherence was also associated with discrepancies between subjective and (semi)objective disease outcomes, and often against required treatment intensification. These results may indicate that adherence to DAS-steered protocols appears to depend in part on the height of the target and on how physicians perceive the DAS reflects RA activity. PMID- 27680541 TI - Carbazole alkaloids from Murraya koenigii trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells. AB - Carbazole alkaloids, a major constituent of Murraya koenigii (L.) Sprengel (Rutaceae), exhibit biological effects such as anticancer activity via the induction of apoptosis, and they represent candidate chemotherapeutic agents. Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the oral cavity and a growing and serious health problem worldwide. In this study, we investigated the anticancer properties and mechanisms of action of two carbazole alkaloids derived from M. koenigii leaves, mahanine and isomahanine, in the OSCC cell line CLS-354. At 15 MUM, mahanine and isomahanine were cytotoxic to CLS-354 cells, triggering apoptosis via caspase-dependent and -independent mechanisms. Autophagosomes, visualised using monodansylcadaverine (MDC) labelling, were numerous in carbazole alkaloid-treated cells. Mahanine and isomahanine markedly induced the expression of the autophagosome marker microtubule-associated protein 1 light chain 3, type II (LC3B-II). Genetic and chemical inhibition of autophagy via silencing of the Autophagy protein 5 gene and exposure to bafilomycin A1 (BafA1), respectively, did not arrest carbazole alkaloid-induced apoptosis, indicating that it occurs independently of autophagic activation. Surprisingly, both carbazole alkaloids caused increased accumulation of p62/sequestosome1 (p62/SQSTM1), with coordinated expression of LC3B-II and cleaved caspase-3, suggesting inhibition of autophagic flux. Our results suggest that inhibition of autophagic flux is associated with carbazole alkaloid-induced apoptosis. Our findings provide evidence of a novel cytotoxic action of natural carbazole alkaloids and support their use as candidate chemotherapeutic agents for the treatment of OSCC. PMID- 27680542 TI - The physiological basis and measurement of heart rate variability in humans. AB - Cardiovascular variabilities were recognized over 250 years ago, but only in the past 20 years has their apparent utility come to be appreciated. Technological advancement has allowed precise measurement and quantification of short-term cardiovascular fluctuations; however, our understanding of the integrated mechanisms which underlie these oscillations is inadequate for their widespread application. Both autonomic branches, the parasympathetic and sympathetic nervous system, are key determinants of the magnitude of these spontaneous cardiovascular fluctuations. Heart rate variability can be an indicator of an individual cardiovascular condition. In this review, we will discuss the two primary rhythmic oscillations that underlie the complexity of the heart rate waveform. The first oscillation occurs over several cardiac cycles, is respiratory related, and termed respiratory sinus arrhythmia. The second oscillation occurs at an approximate 10 s cycle. Due to the closed-loop nature of the control system of cardiovascular oscillations, it is difficult to define specific relations among cardiovascular variables. In this review, we will present the feedforward and feedback mechanism that underlie both oscillations and their implication as quantitative measures of autonomic circulatory control. We will also review the various methodologies to assess them. PMID- 27680543 TI - [Speech audiometry, speech perception and cognitive functions. German version]. AB - Examination of cognitive functions in the framework of speech perception has recently gained increasing scientific and clinical interest. Especially against the background of age-related hearing impairment and cognitive decline potential new perspectives in terms of better individualisation of auditory diagnosis and rehabilitation might arise. This review addresses the relationships of speech audiometry, speech perception and cognitive functions. It presents models of speech perception, discusses associations of neuropsychological with audiometric outcomes and shows recent efforts to consider cognitive functions with speech audiometry. PMID- 27680544 TI - [Simulation in surgical training]. AB - BACKGROUND: Patient safety during operations hinges on the surgeon's skills and abilities. However, surgical training has come under a variety of restrictions. To acquire dexterity with decreasingly "simple" cases, within the legislative time constraints and increasing expectations for surgical results is the future challenge. OBJECTIVES: Are there alternatives to traditional master-apprentice learning? MATERIALS AND METHODS: A literature review and analysis of the development, implementation, and evaluation of surgical simulation are presented. RESULTS: Simulation, using a variety of methods, most important physical and virtual (computer-generated) models, provides a safe environment to practice basic and advanced skills without endangering patients. These environments have specific strengths and weaknesses. CONCLUSIONS: Simulations can only serve to decrease the slope of learning curves, but cannot be a substitute for the real situation. Thus, they have to be an integral part of a comprehensive training curriculum. Our surgical societies have to take up that challenge to ensure the training of future generations. PMID- 27680545 TI - [Drug therapy of otorhinolaryngological diseases in pregnancy : An update]. AB - The majority of women take at least one form of medication during pregnancy. Due to often discrepant information about the risk assessment of pharmaceuticals during pregnancy, physicians are often beset by uncertainty with respect to prescription and the fear of medicolegal consequences is high. As prospective clinical trials on drug safety during pregnancy are prohibited due to ethical reasons and animal studies are of limited applicability to humans, drug recommendations often only rely on observational data. An objective examination of the topic not only contributes to effective treatment of illnesses in pregnancy but also prevents impairment of fetal outcome by omission of necessary maternal treatment. The aim of this article is to give a structured presentation of medications that can be used during pregnancy for treating medical conditions of the ear, nose and throat, in the sense of practical guidelines. PMID- 27680546 TI - Contraction of endothelial cells: 40 years of research, but the debate still lives. AB - Force generation in non-muscle cells is vital for many cellular and tissue functions. Force-generating mechanisms include actomyosin-mediated contraction, actin polymerization that drives plasma membrane protrusions and filopodia as well as kinesin- and dynein-controlled transport of vesicles and organelles along the microtubule cytoskeleton. The actomyosin-mediated contractility and actin remodeling in both epithelium and endothelium were shown to have significant impact on cell migration, shape change and formation and control of intercellular junctions. In endothelium, contraction is supposed to control permeability for fluid and solutes. However, recent studies demonstrated the constitutive appearance of junction-associated intermittent lamellipodia (JAIL) that drive vascular endothelial cadherin (VE-cadherin) dynamics and control endothelial permeability. Since thrombin blocks JAIL formation and thus increases endothelial permeability, the concept of a simple Rho GTPase-controlled contraction, which is supposed to open endothelial junctions, becomes challenged. Furthermore, specific tyrosine phosphorylation sites of VE-cadherin and catenins have been shown to be involved in control of VE-cadherin-mediated cell adhesion. How the causal mechanistic interdependency between contractility, VE-cadherin and catenin phosphorylation and JAIL-mediated dynamic remodeling of VE-cadherin is regulated is still an open question and needs to be further addressed. PMID- 27680548 TI - Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction. AB - Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function. Mst1 overexpression deceased CMECs autophagy as evidenced by decreased LC3 expression and enhanced protein aggregation when subjected to high glucose culture. Mst1 knockout improved cardiac microvessel integrity and enhanced cardiac functions in diabetic mice. Mst1 knockdown up regulated autophagy as indicated by more typical autophagosomes and increased LC3 expression in CMECs subjected to high glucose cultures. Mst1 knockdown also promoted autophagic flux in the presence of bafilomycin A1. Mst1 overexpression increased CMECs apoptosis, whereas Mst1 knockout decreased CMECs apoptosis. Sirt1 knockout abolished the effects of Mst1 overexpression in cardiac microvascular injury and cardiac dysfunction. In conclusion, Mst1 knockout preserved cardiac microvessel integrity and improved cardiac functions in diabetic mice. Mst1 decreased sirt1 activity, inhibited autophagy and enhanced apoptosis in CMECs, thus participating in the pathogenesis of diabetic coronary microvascular dysfunction. PMID- 27680550 TI - Etiology and diagnosis of stroke in the young adult. AB - Stroke is commonly thought of as a disease of the elderly, but it should be understood that stroke also occurs in young adults. Furthermore, it is important to appreciate the differences in epidemiology of these cohorts in order to effectively care for young adults with stroke. Diagnostic imaging has proven to be extremely valuable in management of these patients, in particular in differentiating hemorrhagic from ischemic causes of stroke. PMID- 27680549 TI - The impact of a formal complaint on Dutch dentists' professional practice: a survey study. AB - BACKGROUND: A complaint from a patient can have a serious impact on the well being of dentists. Little is known, however, about the nature and the extent of this impact. METHODS: Therefore in 2013 an anonymous survey was conducted among 955 dentists and dental specialists who were involved in a complaints procedure dealt with by the Complaints Committee of the Royal Dutch Dental Association (KNMT) in the period of mid-2008 to mid-2013. RESULTS: In total 413 (43 %) of these dentists participated in the study. As a result of a formal complaint 71 % of the respondents experienced a considerable impact in their professional practising, while 52 % stated that it had (also) seriously influenced their attitude towards colleagues and patients. Furthermore, 60 % (also) mentioned effects of a complaints procedure regarding their mental and/or physical well being. CONCLUSIONS: Being confronted with a formal complaint from a patient leads to a considerable impact on dentists' professional practice and personal well being. It is remarkable this did not only pertain to a 'negative' impact, but also to a 'positive' impact. Despite unpleasant feelings, several dentists regarded the complaint as a 'wake-up call'. Furthermore, given the relatively high number of successful mediation attempts it can be concluded that this form of complaint handling appears to be a successful way of solving problems that have arisen between patients and dentists. PMID- 27680547 TI - Chemosensory epithelial cells in the urethra: sentinels of the urinary tract. AB - A peculiar cell type of the respiratory and gastrointestinal epithelia, originally termed "brush cell" or "tuft cell" by electron microscopists because of its apical tuft of microvilli, utilizes the canonical bitter taste transduction cascade known from oropharyngeal taste buds to detect potential hazardous compounds, e.g. bacterial products. Upon stimulation, this cell initiates protective reflexes and local inflammatory responses through release of acetylcholine and chemokines. Guided by the understanding of these cells as sentinels, they have been newly discovered at previously unrecognized anatomical locations, including the urethra. Solitary cholinergic urethral cells express canonical taste receptors and are polymodal chemosensors for certain bitter substances, glutamate (umami) and uropathogenic Escherichia coli. Intraurethral bitter stimulation triggers cholinergic reflex activation of bladder detrusor activity, which is interpreted as cleaning flushing of the urethra. The currently known scenario suggests the presence of at least two more urethral chemosensory cell types: non-cholinergic brush cells and neuroendocrine serotonergic cells. The potential implications are enormous and far reaching, as these cells might be involved in monitoring and preventing ascending urinary tract infection and triggering of inappropriate detrusor activity. However, although appealing, this is still highly speculative, since the actual number of distinct chemosensory cell types needs to be finally clarified, as well as their embryological origin, developmental dynamics, receptor equipment, modes of signalling to adjacent nerve fibres and other cells, repertoire of chemo- and cytokines, involvement in pathogenesis of diseases and many other aspects. PMID- 27680552 TI - The young stroke patient: A need for specialized group support systems. AB - Young stroke patients (<65 years of age) account annually for more than one quarter of the people who survive a stroke. This article demonstrates the necessity of providing ongoing stroke support networks for these young stroke survivors and their families and caregivers. Through a support group system, members have the opportunity to access education, socialization, emotional support, and community interaction. The authors utilized a survey format to interview young stroke survivors who belong to support groups and leaders of stroke support groups. The survey results detail common practices of Chicago metropolitan area stroke support groups, their typical formats, and their stated goals. These results document a definitively expressed need for young survivors to participate in peer groups addressing their different set of circumstances. PMID- 27680551 TI - Assessment of the needs of the young stroke survivor. AB - As part of program planning efforts by the RIC Stroke Team, convenience samples of 100 young (<60 years old) stroke survivors and 65 referring physicians were surveyed to determine the unique needs ofthis patient group. The correlation between survivors' and physicians' rankings of programs/activities value was not significant. Survivors ranked exercise/fitness, education/information, individual counseling, stress management, and recreation/social programs as the five most valuable programs. Physicians ranked education/ information, individual counseling, sexual, vocational, and family adjustment programs as the five most valuable. Other comparisons and program planning implications are analyzed and discussed. PMID- 27680553 TI - Stroke during pregnancy. AB - Stroke during pregnancy poses a challenge to the rehabilitation team. A 10-year review of one hospital's records revealed five pregnancies complicated by stroke. The mean age was 29 years (range, 21 to 35 years). Cerebrovascular accidents associated with pregnancy may be due to many causes, with intracranial hemorrhage due to arteriovenous malformation or aneurysm, arterial occlusion due to thrombosis or embolus, venous thrombosis, and vasculitis representing the more common etiologies. Three of the strokes in this study were due to intracranial hemorrhage, and two were due to thrombosis secondary to CNS vasculitis. Two case studies and a review of the literature are presented. Stroke during pregnancy represents a high-risk obstetrical situation that may complicate the rehabilitation process. PMID- 27680554 TI - Child care and parenting issues for the young stroke survivor. AB - Parenting is a complex and challenging task for any parent and it becomes even more complicated for an individual who experiences a disability. Literature addressing the parenting role for individuals who have experienced a stroke is limited. This article provides information on evaluation tools available for assessing an individual's ability to perform child care tasks and intervention strategies such as adaptive techniques and equipment for maximizing ability and promoting safe performance of child care tasks by the individual who has experienced a stroke. Product and literature resources that can be used by either the health professional or the parent with a stroke to facilitate parenting and child care task performance are included. PMID- 27680555 TI - Preparing the young stroke survivor for return to work. AB - Preparing the young stroke survivor for work is an essential aspect of the rehabilitation process. This unique prevocational program, the Functional Occupations Program (FOP), is designed to provide outpatient, interdisciplinary group services to those who want to return to work or an occupation after cerebrovascular accident (CVA) or other devastating injuries. In the past 3.5 years of the program, 39 CVAs were seen. Preliminary outcome measures indicate that 20% of the CVAs served in year 3 and beginning of year 4 returned to work, with 58% of those individuals in blue collar jobs. PMID- 27680556 TI - Vocational outcome after stroke. AB - This article reviews the literature on vocational outcome after stroke and discusses reasons for the minimal use of vocational outcome measures in stroke rehabilitation research. A vocational function measurement tool is proposed. The vocational rehabilitation process and experience of the Young Stroke Program at New England Rehabilitation Hospital are described, and determinants of success or failure in vocational rehabilitation after stroke as described in the medical literature are reviewed. The impact of the Americans with Disabilities Act of 1990 and of changes in health care funding on vocational outcomes after stroke are discussed. PMID- 27680557 TI - Observations of a young stroke patient. PMID- 27680561 TI - From the editor. PMID- 27680558 TI - Diabetes mellitus: Incidence and influence on stroke rehabilitation and outcome. PMID- 27680559 TI - Poststroke seizures. PMID- 27680562 TI - Letters to the editor. PMID- 27680563 TI - Fascin Induces Epithelial-Mesenchymal Transition of Cholangiocarcinoma Cells by Regulating Wnt/beta-Catenin Signaling. AB - BACKGROUND Our preliminary study suggested that the expression of Fascin was increased in cholangiocarcinoma, which indicating poor prognosis The present study aimed to explore the roles and mechanisms of Fascin during the progression of cholangiocarcinoma. MATERIAL AND METHODS We evaluated the knockdown effect of endogenous Fascin expression by Short hairpin RNA (shRNA) in QBC939 cells. Cell proliferation was confirmed by MTS assay. Migration and invasion assay was used to examine the cell invasive ability. Tumorigenesis abilities in vivo were analyzed with a xenograft tumor model. Western blot analysis was used to test epithelial-mesenchymal transition (EMT) biomarkers and critical proteins in the Wnt/beta-catenin signaling pathway. RESULTS shRNA-mediated gene knockdown of Fascin significantly inhibited cell proliferation, invasion, and EMT, and shRNA Fascin markedly inhibited the xenograft tumor volume. Silencing of Fascin up regulated phosphorylation of beta-catenin and decreased its nuclear localization. Additionally, knockdown of Fascin led to the upregulation of beta-catenin and E cadherin expression in plasma membrane fraction of QBC939 cells. CONCLUSIONS Our data indicate a key role of Fascin in cell proliferation, migration, and invasion in cholangiocarcinoma. Fascin promotes EMT of cholangiocarcinoma cells, in part through regulating Wnt/beta-catenin signaling. PMID- 27680565 TI - Erratum to: Using ApoE Genotyping to Promote Healthy Lifestyles in Finland - Psychological Impacts: Randomized Controlled Trial. PMID- 27680564 TI - Erratum to: Heregulin-1beta and HER3 in hepatocellular carcinoma: status and regulation by insulin. PMID- 27680566 TI - Predictive Genetic Testing of Children for Adult-Onset Conditions: Negotiating Requests with Parents. AB - Healthcare professionals (HCPs) regularly face requests from parents for predictive genetic testing of children for adult-onset conditions. Little is known about how HCPs handle these test requests, given that guidelines recommend such testing is deferred to adulthood unless there is medical benefit to testing before that time. Our study explored the process of decision-making between HCPs and parents. Semi-structured interviews were conducted with 34 HCPs in 8 regional genetic services across the UK, and data were thematically analysed. We found that instead of saying 'yes' or 'no' to such requests, many HCPs framed the consultation as an opportunity to negotiate the optimal time of testing. This, they argued, facilitates parents' considered decision-making, since parents' eventual decisions after requesting a test was often to defer testing their child. In cases where parents' requests remained a sustained wish, most HCPs said they would agree to test, concluding that not testing would not serve the child's wider best interest. As a strategy for determining the child's best interest and for facilitating shared decision-making, we recommend that HCPs re-frame requests for testing from parents as a discussion about the optimal time of testing for adult-onset disease. PMID- 27680567 TI - Decisions Regarding Pregnancy Termination Due to beta-Thalassemia Major: a Mixed Methods Study in Sistan and Baluchestan, Iran. AB - In the present study, an embedded design was applied in order to conduct a one year cross-sectional audit of chorionic villus sampling (CVS) and foetal outcomes affected by beta-thalassemia major (beta-TM) in a prenatal diagnosis (PND) setting. In addition, we explored the decisions regarding pregnancy termination among women whose pregnancy (or child) was affected by beta-TM. In the quantitative phase, the available data in the clients' medical records were analysed, while the qualitative phase was performed using a grounded theory method. Interviews were performed with nine pregnant women who had decided against pregnancy termination despite positive CVS results, 11 mothers who had admitted their child to the thalassemia ward for blood transfusion, and 19 mothers who had received positive CVS results and had decided against pregnancy termination in the preceding year. Over one year, 18.6 % of women decided against pregnancy termination despite positive CVS results. Two main themes related to decisions against pregnancy termination emerged from the qualitative data: 1) Cognitive factors (questioning the reliability of the tests or doubts about the accuracy of the results, understanding disease recurrence, curability, perceived severity of the disease, and lack of "real-life experiences"); and 2) Sociocultural responsiveness (family opposition, responsibility before God, and self-responsiveness). All of the mentioned factors could intensify fear of abortion in couples due to possible regret, and encourage a decision against pregnancy termination. PMID- 27680569 TI - Improving Collaborative Behaviour Planning in Adult Auditory Rehabilitation: Development of the I-PLAN Intervention Using the Behaviour Change Wheel. AB - Background: The consequences of poorly managed hearing loss can be ameliorated with hearing aid use but rates of use are sub-optimal. The impact of audiologist behaviour on subsequent use, particularly over the long term, is unknown. Purpose: This study aimed to describe the role of the behaviour change wheel in developing an intervention to introduce and embed particular clinical behaviours into adult hearing aid fitting consultations, within the framework of the Medical Research Council guidance on complex interventions. Methods: Following the steps of the behaviour change wheel, audiologist behaviours that might influence hearing aid use were identified based on a systematic review and qualitative work with audiologists. An analysis, using the COM-B model, identified potential drivers of the target behaviours. This was used to select intervention functions and behaviour change techniques likely to influence behaviour in this context. Results: The target behaviours were as follows: giving information about the benefits of hearing aid use and the negative consequences of non-use, providing prompts for use and engaging in collaborative behavioural planning for use. The behavioural analysis suggested that psychological capability, opportunity and motivation were potential drivers of these behaviours. The intervention functions of education, coercion, training, environmental restructuring, modelling and enablement were selected and combined to develop a single complex intervention that seeks to address the target behaviours. PMID- 27680568 TI - Physical Activity in Older Adults: an Ecological Approach. AB - BACKGROUND: Studies identifying correlates of physical activity (PA) at all levels of the ecological model can provide an empirical basis for designing interventions to increase older adults' PA. PURPOSE: Applying ecological model principles, this study concurrently examined individual, psychosocial, and environmental correlates of older adults' PA to determine whether built environment factors contribute to PA over and above individual/demographic and psychosocial variables. METHODS: Using a cross-sectional observational design, 726 adults, aged >=66 years, were recruited from two US regions. Explanatory variables included demographics, self-efficacy, social support, barriers, and environmental variables measured by using geographic information systems (GIS) and self-report. Outcomes included reported walking for errands and leisure/exercise and accelerometer-measured daily moderate to vigorous PA (MVPA). Analyses employed mixed-model regressions with backward elimination. RESULTS: For daily MVPA, the only significant environmental variable was GIS-based proximity to a park (p < 0.001) after controlling for individual/demographic and psychosocial factors. Walking for errands was positively related to four environmental variables: reported walking/cycling facilities (p < 0.05), GIS based intersection density (p < 0.01), mixed land use (p < 0.01), and private recreation facilities (p < 0.01). Walking for leisure/exercise was negatively related to GIS-based mixed land use (p < 0.05). Non-Hispanic white race/ethnicity, self-efficacy, and social support positively related to all three PA outcomes (p < 0.05). CONCLUSIONS: Correlates of older adults' PA were found at all ecological levels, supporting multiple levels of influence and need for multilevel interventions. Environmental correlates varied by PA outcome. Walking for errands exhibited the most environmental associations. PMID- 27680571 TI - Influence of Pulse Repetition Frequency on 3-D Power Doppler Quantification. AB - Three-dimensional power Doppler quantification has limited application because of its high dependency on attenuation. The purpose of the study described here was to assess if different degrees of attenuation, depending on pulse repetition frequency (PRF) adjustment, alter 3-D power Doppler quantification in a region of 100% moving blood when using vascularization index, flow index and vascularization flow index (VFI). A cubic-shaped gelatin phantom with a 1.8-mm internal-diameter silicon tube was used. The tube, placed at 45 degrees to the phantom's surface, was filled with blood-mimicking fluid with as constant maximum velocity of 30 cm/s. Two different attenuation blocks (low and high attenuation) were alternatively placed between the phantom and the transvaginal transducer. One single observer acquired 10 data sets for each PRF level from 0.3 to 7.5 kHz, using the high- and low-attenuation blocks, for a total of 200 3-D power Doppler data sets. We assessed VFI from 1.5-mm-diameter spherical samples, virtually placed inside the tube, always at the same position. No difference was noted between high- and low-attenuation VFI values when using a PRF of 0.3 kHz. As PRF increased, it was observed that VFI quantification progressively differed between low and high attenuation. Also, a slope on VFI values for both high- and low attenuation models could be observed when increasing PRF, particularly above 4.0 kHz. We concluded that PRF adjustment is very relevant when using VFI to quantify 3-D power Doppler signal. PMID- 27680570 TI - Anti-PD-1 inhibits Foxp3+ Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model. AB - The co-inhibitory molecule PD-1 suppresses T cell responses and has been targeted in the treatment of cancer. Here, we examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumour vaccine-induced protective immunity. A significantly higher proportion of tumour-resident T cells expressed PD-1 and Foxp3 compared with T cells in the tumour circulation or draining lymph nodes, and this correlated with a lower frequency of IFN-gamma- and TNF-secreting CD8 T cells. Blocking PD-1 with a specific antibody reduced Foxp3+ regulatory T (Treg) cell induction and enhanced proliferation, cytokine production, and tumour killing by CD8 T cells. Treatment of CT26 tumour-bearing mice with anti-PD-1 in combination with a vaccine, comprising heat-shocked irradiated tumour cells and a TLR 7/8 agonist, significantly reduced tumour growth and enhanced survival. Furthermore, surviving mice resisted tumour re-challenge. The rejection of tumours in mice treated with the anti-PD-1 vaccine combination was associated with a reduction in tumour infiltrating Treg cells and enhancement of IFN-gamma-secreting CD8 T cells. Our findings demonstrate that high PD-1 expression correlates with increased tumour infiltrating Treg cells and reduced effector T cells and that when combined with a potent antigen-adjuvant combination, blocking PD-1 effectively enhances anti tumour immunity. PMID- 27680573 TI - The Modern Face of Synthetic Heterocyclic Chemistry. AB - The synthesis of heterocycles is arguably one of the oldest and at the same time one of the youngest disciplines of organic chemistry. Groundbreaking principles to form heterocycles, mainly by condensation reactions, were recognized in the beginning of the 19th century, and many of the classical reactions discovered at that time are still of great value today. In the 21st century, the wealth of synthetic methodology toward heterocycles is overwhelming, and catalysis, in particular, as one of the cornerstones of green and sustainable chemistry has contributed in a major way to these developments. This perspective tries the impossible by discussing some recent advances in the construction of heterocycles, focusing on catalytic methodology. We are aware that we do not come close to giving adequate credit to the great creativity of chemists in the field. PMID- 27680572 TI - Influence of Donor Age and Stimulation Intensity on Osteogenic Differentiation of Rat Mesenchymal Stromal Cells in Response to Focused Low-Intensity Pulsed Ultrasound. AB - A focused low-intensity pulsed ultrasound (FLIPUS) was used to investigate the effects of stimulation period, acoustic intensity and donor age on the osteogenic differentiation potential of rat mesenchymal stromal cells (rMSCs). rMSCs from 3- and 12-mo-old female Sprague Drawly rats were isolated from bone marrow and stimulated 20 min/d with either 11.7 or 44.5 mW/cm2 (spatial average temporal average intensity) for 7 or 14 d. Osteogenic differentiation markers, i.e., Runt related transcription factor 2 (RUNX2), osteocalcin (OCN) and degree of matrix calcification were analyzed. On day 7 of stimulation, OCN gene expression was enhanced 1.9-fold in cells from young rats when stimulated with low intensity. The low intensity also led to a 40% decrease in RUNX2 expression on day 7 in aged cells, whereas high intensity enhanced expression of RUNX2 on day 14. FLIPUS treatment with low intensity resulted in a 15% increase in extracellular matrix mineralization in young but not old rMSCs. These differences suggest the necessity of a donor-age related optimization of stimulation parameters. PMID- 27680574 TI - Tricuspid atresia associated with aortopulmonary window: diagnostic and therapeutic dilemmas. AB - The association of tricuspid atresia with aortopulmonary window is exceptionally rare. We report a patient with tricuspid atresia, normally related great arteries, non-restrictive ventricular septal defect, and no pulmonary stenosis (type IC) with an aortopulmonary window who underwent successful initial surgical palliation. The unique anatomical feature of this case, other than the presence of the aortopulmonary window, was the absence of pulmonary stenosis at the level of either the ventricular septal defect or the pulmonary valve. All other reported cases have described some degree of restriction of anterograde pulmonary flow due to pulmonary stenosis or atresia. PMID- 27680575 TI - Switching the Immunogenicity of Peptide Assemblies Using Surface Properties. AB - Biomaterials created from supramolecular peptides, proteins, and their derivatives have been receiving increasing interest for both immunological applications, such as vaccines and immunotherapies, as well as ostensibly nonimmunological applications, such as therapeutic delivery or tissue engineering. However, simple rules for either maximizing immunogenicity or abolishing it have yet to be elucidated, even though immunogenicity is a prime consideration for the design of any supramolecular biomaterial intended for use in vivo. Here, we investigated a range of physicochemical properties of fibrillized peptide biomaterials, identifying negative surface charge as a means for completely abolishing antibody and T cell responses against them in mice, even when they display a competent epitope. The work was facilitated by the modularity of the materials, which enabled the generation of a set of co assembled fibrillar peptide materials with broad ranges of surface properties. It was found that negative surface charge, provided via negatively charged amino acid residues, prevented T cell and antibody responses to antigen-carrying assemblies because it prevented uptake of the materials by antigen-presenting cells (APCs), which in turn prevented presentation of the epitope peptide in the APCs' major histocompatibility class II molecules. Conversely, positive surface charge augmented the uptake of fibrillized peptides by APCs. These findings suggest that some surface characteristics, such as extensive negative charge, should be avoided in vaccine design using supramolecular peptide assemblies. More importantly, it provides a strategy to switch off potentially problematic immunogenicity for using these materials in nonimmunological applications. PMID- 27680576 TI - Changes in cardiac function and structure in newly diagnosed Graves' disease. A conventional and 2D-speckle tracking echocardiography study. AB - Overproduction of thyroid hormones leads to structural as well as functional cardiac changes. Conventional echocardiography but also recently developed sophisticated two-dimensional echocardiography speckle (2D-STE) tracking allow elaborate evaluation of these changes. Our purpose was to investigate the effects of thyroid hormones overproduction on the heart in patients with Graves' disease and changes that occur after 6 months thyrostatic therapy. We conducted a prospective, case-control study of 6 months duration. Full echocardiographic assessment at diagnosis and after 6 months of thyrostatic therapy were performed in 44 patients with Graves' disease, aged 37.6 +/- 9.1 years. Additionally, 43 euthyroid controls were studied for the same time period. Left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were higher in the patient group while triscupid annular plane systolic excursion (TAPSE) was lower in the patient group. Moreover, left ventricular (LV) mass index and left atrium (LA) volume index were higher in the Graves' disease group. Diastolic impairment as assessed with conventional echocardiography including tissue Doppler was present in the patient group (E/A ratio 0.87 +/- 0.10,). 2D STE analysis, revealed an increase in the strain rate at the isovolumic relaxation time (SRIVRT, 0.310 +/- 0.07 patients versus 0.298 +/- 0.09 s-1 controls). Improvement in diastolic and right systolic function as well as in left ventricular structural parameters was observed after restoration of euthyroidism (E/A ratio from 0.87 +/- 0.10 versus 0.9 +/- 0.08, p < 0.05). Patients with newly diagnosed Graves' showed an improvement in diastolic function, right systolic function and structural parameters after 6 months of thyrostatic treatment. PMID- 27680577 TI - Leptospirosis in a British soldier after travel to Borneo. AB - Undifferentiated febrile illness in a returning soldier is a common problem encountered by serving medical officers. A 32-year-old soldier presented to Birmingham Heartlands Hospital with fever and acute kidney injury after return from Borneo. Leptospirosis was suspected and empirical antibiotics were started before subsequent confirmation by serology and PCR. Leptospirosis is common in South-East Asia, and troops exercising in jungle areas, and in the UK, are at risk. Advice, including inpatient management when appropriate, is available from the UK Role 4 Military Infectious Diseases and Tropical Medicine Service. PMID- 27680579 TI - The role of decidual NK cells in pregnancies with impaired vascular remodelling. AB - The pathologies of the dangerous pregnancy complications pre-eclampsia (PE) and fetal growth restriction (FGR) are established in the first trimester of human pregnancy yet we know little of how this happens. Finely tuned interactions between maternal and placental cells are essential for pregnancy to progress without complications; however, the precise nature of this cross-talk and how it can go wrong are crucial questions that remain to be answered. This review summarises recent studies examining the role played by natural killer cells in regulating normal placentation and remodelling. Their involvement when it is impaired in PE/FGR pregnancies will additionally be discussed. PMID- 27680578 TI - Curing neurophobia in medical schools: evidence-based strategies. AB - Medical students often perceive neurology as the most difficult medical specialty. This perception is described as 'neurophobia' in the medical literature. Several studies have cited poor teaching, complex examination, and separation of basic and clinical sciences as major factors in the development of neurophobia. These negative perceptions can have serious implications, such as decreasing the students' desire to consider neurology as a future career and increasing referrals from other specialists to avoid dealing with neurological conditions. Faced with increasing demands of healthcare systems and the global burden of neurological conditions, there is a rising need for further research and innovative strategies to improve students' perceptions of clinical neurology. This review discusses evidence-based recommendations and educational interventions to cure neurophobia in medical education. PMID- 27680580 TI - Aortic root stiffness affects the kinematics of bioprosthetic aortic valves. AB - Objectives: In this study, the influence of aortic root distensibility on the haemodynamic parameters and valve kinematics of a bioprosthetic aortic valve was investigated in a controlled in vitro experiment. Methods: An Edwards INTUITY Elite 21 mm sutureless aortic valve (Edwards Lifesciences, Irvine, CA, USA) was inserted in three transparent aortic root phantoms with different wall thicknesses (0.55, 0.85 and 1.50 mm) mimicking different physiological distensibilities. Haemodynamic measurements were performed in an in vitro flow loop at heart rates of 60, 80 and 100 bpm with corresponding cardiac outputs of 3.5, 4.0 and 5.0 l/min and aortic pressures of 100/60, 120/90 and 145/110 mmHg, respectively. Aortic valve kinematics were assessed using a high-speed camera. The geometric orifice area (GOA) was measured by counting pixels in the lumen of the open aortic valve. The effective orifice area (EOA) was calculated from the root-mean-square value of the systolic aortic valve flow rate and the mean systolic trans-valvular pressure gradient. Results: The tested aortic root phantoms reproduce physiological distensibilities of healthy individuals in age groups ranging from 40 to 70 years (+/-10 years). The haemodynamic results show only minor differences between the aortic root phantoms: the trans-valvular pressure gradient tends to increase for stiffer aortic roots, whereas the systolic aortic valve flow rate remains constant. As a consequence, the EOA decreased slightly for less distensible aortic roots. The GOA and the aortic valve opening and closing velocities increase significantly with reduced distensibility for all haemodynamic measurements. The resulting mean systolic flow velocity in the aortic valve orifice is lower for the stiffer aortic root. Conclusions: Aortic root distensibility may influence GOA and aortic valve kinematics, which affects the mechanical load on the aortic valve cusps. Whether these changes have a significant effect on the onset of structural valve deterioration of bioprosthetic heart valves needs to be further investigated. PMID- 27680581 TI - The effect of cement augmentation and anteromedial plating on proximal humerus allograft reconstruction. AB - BACKGROUND: Limb salvage following the resection of tumor from the proximal part of the humerus, poses many challenges, and there is no consensus regarding the best reconstructive technique after proximal humerus resection. The aim of this study was to evaluate the effect of anteromedial placing of the plate in the absence of deltoid muscle and cement augmentation on the functional outcome, complication rate and survival of proximal humerus allograft reconstruction. PATIENTS AND METHODS: A number of 36 osteoarticular allograft reconstructions of proximal humerus were included in final study. In 26 cases, medullary canal of the allograft was filled by cement and the complication rate and survival was compared to non-cemented allografts. In addition, anteromedial placement of plate was applied for all resection type IB (18 cases), in which the deltoid muscle was resected. The mean follow-up of patients was 46 months. RESULTS: In total, 12 complications including 3 fractures, 4 resorptions, 3 infections and 2 nonunions were reported. Complication rates were significantly lower in cemented allografts (p = 0.001). Five year survival rates of cemented and non-cemented allografts were found to be 82% and 70%, respectively. The mean MSTS score was 84.9%, ranging 76-90. CONCLUSION: According to our results, cement augmentation improves survival and reduces the complication rate of allografts. Moreover, our results showed that anteromedial placing of the plate in resection type IB could improve the functional outcome of allografts. However, the detailed effect of anteromedial plating should be further investigated in future studies. PMID- 27680582 TI - Neuroblastoma metastasis to bone requiring differentiation from septic arthritis of the hip. Report of 2 cases. PMID- 27680583 TI - Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline. PMID- 27680584 TI - Further Evaluation of the Use of Multiple Schedules for Behavior Maintained by Negative Reinforcement. AB - One potential limitation of functional communication training (FCT) is that after the functional communication response (FCR) is taught, the response may be emitted at high rates or inappropriate times. Thus, schedule thinning is often necessary. Previous research has demonstrated that multiple schedules can facilitate schedule thinning by establishing discriminative control of the communication response while maintaining low rates of problem behavior. To date, most applied research evaluating the clinical utility of multiple schedules has done so in the context of behavior maintained by positive reinforcement (e.g., attention or tangible items). This study examined the use of a multiple schedule with alternating Fixed Ratio (FR 1)/extinction (EXT) components for two individuals with developmental disabilities who emitted escape-maintained problem behavior. Although problem behavior remained low during all FCT and multiple schedule phases, the use of the multiple schedule alone did not result in discriminated manding. PMID- 27680586 TI - RNA fluorescence in situ hybridization using 3-cyanovinylcarbazole modified oligodeoxyribonucleotides as photo-cross-linkable probes. AB - Photo-cross-linkable fluorescent oligodeoxyribonucleotides having 3 cyanovinylcarbazole nucleoside were applied to fluorescence in situ hybridization (FISH) based 16S rRNA detection in Escherichia coli cells. As the photo-cross linked probe/rRNA hybrid was stable under the denaturing condition, decrease of the fluorescence signal through the washing process was prevented. The thermally irreversible hybridization property also enabled stable hybridization with the structured region on the target RNA, and facilitated design of the sequence for the FISH probe. Further development of the method might contribute to quantitative and stable FISH staining. PMID- 27680585 TI - Evaluation of a Physical Activity Regulation for Child Care in Massachusetts. AB - OBJECTIVES: A number of states have enacted regulations to increase physical activity in children attending child care, but most were not evaluated. In 2010, Massachusetts (MA) enacted a new regulation requiring 60 minutes of light, moderate, and vigorous physical activity (LMVPA) for children in child care; we conducted a prospective evaluation. We hypothesized that MA centers would comply with the regulation at follow-up, resulting in increases in children's LMVPA. METHODS: We evaluated compliance with the regulation in MA using Rhode Island (RI) as the comparison. We measured physical activity in a longitudinal sample of 20 centers and cross-sectional samples of 180 children per state three times before and three times after the regulation took effect. We assessed physical activity using the Observation System for Recording Activity in Preschoolers. We conducted difference-in-differences tests to evaluate changes in LMVPA in MA compared with RI from baseline to follow-up. RESULTS: Children were active for at least 60 minutes of LMVPA in over 80% of centers at baseline and follow-up in MA and RI. Nevertheless, LMVPA increased in both states. In multivariable adjusted regressions, LMVPA increased from baseline to follow-up [MA estimate 38.1 minutes; confidence interval (CI): 28.6, 47.5; p <= 0.0001; and RI estimate 42.7 minutes; CI: 35.2, 50.1; p <= 0.0001]. The average difference-in-differences estimate indicated no difference in MA compared with RI (estimate -4.6 minutes; CI: -16.6, 7.5; p = 0.46) since LMVPA increased comparably in both states. CONCLUSIONS: Although LMVPA increased in MA, we observed similar changes in RI. Thus, other factors could have influenced children's physical activity. PMID- 27680587 TI - Allyl and prenyl ethers of mansonone G, new potential semisynthetic antibacterial agents. AB - Four natural 1,2-naphthoquinones: mansonones C, E, G, and H were isolated from the dichloromethane extract of Mansonia gagei Drumm. heartwoods. Mansonone G was further converted to eight ether and four ester analogues. The structures of mansonones and the analogues were well-confirmed by spectroscopic techniques. All compounds were evaluated for their antibacterial activity against Gram-positive and negative bacteria. Further modification of mansonone G furnished certain analogues displaying better activity than natural mansonones. Particularly, allyl and prenyl ethers of mansonone G exhibited better activity against Staphylococcus aureus with MIC sixty-four times better than their natural compound. PMID- 27680589 TI - Anti-inflammatory activity effect of 2-substituted-1,4,5,6 tetrahydrocyclopenta[b]pyrrole on TPA-induced skin inflammation in mice. AB - 2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole, a key structural moiety exiting in many bioactive molecules, has been shown to have excellent selective activity on COX-2. In the present study, the anti-inflammatory activity and the underlying molecular mechanism of 2-substituted-1,4,5,6 tetrahydrocyclopenta[b]pyrrole on skin inflammation were assessed by 12-O tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Most of the compounds showed anti-inflammatory activity on TPA-induced skin inflammation. The anti-inflammatory activity of compound 4 showed higher anti-inflammatory activity than celecoxib (3.2-fold). Compound 4 pretreatment resulted in markedly suppression of TPA-induced IL-1beta, IL-6, TNF-alpha, and COX-2, respectively. Furthermore, the mechanical study indicated that the anti-inflammatory activity of compound 4 was associated with its ability to inhibit activation of factor kappa-kappaB (NF-kappaB) by blocking IkappaB kinase (IKK) activities. Accordingly, compound 4 could be used as a potential anti-inflammatory agent for skin inflammation. PMID- 27680588 TI - Structure-activity relationships of proline modifications around the tetracyclic indole class of NS5A inhibitors. AB - We describe the impact of proline modifications, in our tetracyclic-indole based series of nonstructural protein 5A (NS5A) inhibitors, to their replicon profiles. This work identified NS5A inhibitors with an improved and flattened resistance profiles. PMID- 27680590 TI - Structure-activity relationship of cyclic pentapeptide malformins as fibrinolysis enhancers. AB - The formation of blood clots in blood vessels causes severe ischemic diseases such as cerebral infarction and myocardial infarction. While searching for microbial products that increase fibrinolytic activity using an in vitro fibrin degradation assay, we found malformin A1, a disulfide form of cyclo(-d-Cys-d-Cys l-Val-d-Leu-l-Ile-), as an active compound. In this study, we synthesized malformin derivatives using a solid-phase peptide synthesis method and evaluated their fibrinolytic activity and cytotoxicity. Reduction of the disulfide bond and linearization of the cyclic peptide frame decreased the pro-fibrinolytic activity. Substitution of a branched-chain amino acid with lysine resulted in loss of activity. However, protection of the amino group in the lysine derivatives by the tert-butoxycarbonyl (Boc) group rescued the inactivity. Furthermore, the phenylalanine derivatives also exhibited a similar pro fibrinolytic effect compared to malformin A1. These results suggest that the disulfide bond, the cyclic peptide frame, and the bulky hydrophobic side chains play a crucial role in the pro-fibrinolytic activity of malformin. The effective dose of the active derivatives for the in vitro fibrin degradation showed similar ranges (1-5MUM), while the order of cytotoxic potency for the active derivatives was as follows: Phe-derivatives>BocLys-derivatives>malformin A1>reduced form. These results showed no correlation between pro-fibrinolytic activity and cytotoxicity, suggesting the possibility of the synthesis for non-toxic malformin derivatives possessing the activity. PMID- 27680591 TI - Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo. AB - mRNA has broad potential for treating diseases requiring protein expression. However, mRNA can also induce an immune response with associated toxicity. Replacement of uridine bases with pseudouridine has been postulated to modulate both mRNA immunogenicity and potency. Here, we explore the immune response and activity of lipid nanoparticle-formulated unmodified and pseudouridine-modified mRNAs administered systemically in vivo. Pseudouridine modification to mRNA had no significant effect on lipid nanoparticle physical properties, protein expression in vivo, or mRNA immunogenicity compared to unmodified mRNA when delivered systemically with liver-targeting lipid nanoparticles, but reduced in vitro transfection levels. Indicators of a transient, extracellular innate immune response to mRNA were observed, including neutrophilia, myeloid cell activation, and up-regulation of four serum cytokines. This study provides insight into the immune responses to mRNA lipid nanoparticles, and suggests that pseudouridine modifications may be unnecessary for therapeutic application of mRNA in the liver. PMID- 27680592 TI - Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function. AB - GOAL: To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas. BACKGROUND: Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect. STUDY: Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention. RESULTS: Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo). CONCLUSIONS: A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints. PMID- 27680594 TI - Technical standardization of Kasai portoenterostomy for biliary atresia. AB - BACKGROUND: The purpose of this study was to assess the clinical outcome of patients treated with the current technique of Kasai procedure compared with that of those treated with previous procedures. METHODS: We retrospectively assessed the outcomes of 256 patients with biliary atresia who underwent Kasai portoenterostomy at our hospital between 1972 and 2014. Patients were divided into four groups: group 1 (1972-1981, double Roux-en Y, n=91), group 2 (1982 1991, Suruga II, n=80), group 3 (1992-2000, double-valve Roux-en Y, n=46), and group 4 (2001-2014, total removal of the extrahepatic biliary remnants at hepatic capsule and Roux-en Y reconstruction with a spur valve, n=39). Clinical outcomes were compared between the four groups. RESULTS: In groups 1, 2, 3, and 4, the rate of jaundice clearance was 65.9%, 77.5%, 63.0%, and 87.2%, respectively; incidence of early cholangitis was 60.4%, 53.8%, 37.0%, and 23.1%, respectively; requirement for redo Kasai surgery was 15.4%, 37.5%, 17.4%, and 5.1%, respectively; 10-year native liver survival rate was 53.8%, 60.1%, 44.1%, and 73.7%, respectively; and 10-year overall survival rate was 55.0%, 72.3%, 86.7%, and 97.3%, respectively. CONCLUSION: The standardized Kasai procedure was associated with favorable outcomes. Long-term outcomes remain to be evaluated. LEVEL OF EVIDENCE: Case-control/treatment study, level III. PMID- 27680595 TI - Report of the 49th annual meeting of the Pacific Association of Pediatric Surgeons, Kaua'i, Hawai'i, April 24th-28th, 2016. AB - This is the report of the 49th annual meeting of the Pacific Association of Pediatric Surgeons, held at the Grand Hyatt Resort, Kaua'i Island, Hawai'i, USA, April 24th-28th, 2016. PMID- 27680593 TI - Causes and Outcomes of Esophageal Perforation in Eosinophilic Esophagitis. AB - GOALS: To characterize patients who suffer perforation in the context of eosinophilic esophagitis (EoE) and to identify predictors of perforation. BACKGROUND: Esophageal perforation is a serious complication of EoE. MATERIALS AND METHODS: We conducted a retrospective cohort study of the University of North Carolina EoE clinicopathologic database from 2001 to 2014. Subjects were included if they had an incident diagnosis of EoE and met consensus guidelines, including nonresponse to a PPI trial. Patients with EoE who had suffered perforation at any point during their course were identified, and compared with EoE cases without perforation. Multiple logistic regression was performed to determine predictors of perforation. RESULTS: Out of 511 subjects with EoE, 10 (2.0%) had experienced an esophageal perforation. Although those who perforated tended to have a longer duration of symptoms before diagnosis (11.4 vs. 7.0 y, P=0.13), a history of food impaction (odds ratio, 14.9; 95% confidence interval, 1.7-129.2) and the presence of a focal stricture (odds ratio, 4.6; 95% confidence interval, 1.1-19.7) were the only factors independently associated with perforation. Most perforations (80%) occurred after a prolonged food bolus impaction, and only half of individuals (5/10) carried a diagnosis of EoE at the time of perforation; none occurred after dilation. Six patients (60%) were treated with nonoperative management, and 4 (40%) required surgical repair. CONCLUSIONS: Esophageal perforation is a rare but serious complication of eosinophilic esophagitis, occurring in ~2% of cases. Most episodes are due to food bolus impaction or strictures, suggesting that patients with fibrostenotic disease due to longer duration of symptoms are at increased risk. PMID- 27680596 TI - Long-term follow-up for anicteric survival with native liver after redo Kasai: a first report. AB - PURPOSE: We present a first report of the long-term follow-up of biliary atresia (BA) patients who became anicteric with the native liver (ANL; total bilirubin <1.5mg/dL) after redo-Kasai. METHODS: Forty-six redo-Kasai cases (1984-2015) were the subjects for this study. ANL ratios were determined using the Kaplan-Meier estimate. RESULTS: BA type was I (n=3), II (n=1), and III (n=42). Mean ages (initial/redo) at Kasai were 60.3/231.9days, respectively. Jaundice persisted after the initial Kasai in 24/46 cases while 22 had recurrence of jaundice after initially becoming anicteric. After redo, 5/24 of the persistent jaundice cases and 14/22 of the initially anicteric cases became anicteric (p<.05). Of these 19, 7 (one type I, six type III) are currently ANL while the remaining 12 had LTx or died. Morbidity/Complications documented in the 7 post-redo ANL cases after a mean follow-up of 16.7years (range: 10.0-31.1) included 4 episodes of cholangitis, 3 episodes of portal hypertension, 4 episodes of esophageal varices, 3 episodes of splenomegaly, one splenectomy, and 4 episodes of thrombocytopenia. CONCLUSIONS: Ours is the first long-term follow-up study of redo-Kasai cases. We found that the ANL ratio after redo-Kasai was low at 7/46 (15.2%) and that ANL were prone to multiple morbidity. LEVEL OF EVIDENCE: Retrospective comparative study, level III. PMID- 27680597 TI - Role of gabapentin and anticholinergics in management of neurogenic bladder after repair of spina bifida - a randomized controlled study. AB - BACKGROUND: Anticholinergics are well established in the management of neurogenic bladders. However, some patients do have sub-optimal response or severe side effects. This study is designed to assess and compare efficacy of gabapentin with oxybutynin in neurogenic bladders after surgery for spina bifida. METHODS: Patients were randomized into three groups after urodynamic studies and started on oxybutynin, gabapentin, and combination of both, respectively. Thorough clinical and urodynamic reassessment was done at 6months and one year after starting treatment. RESULTS: Forty-four patients (3-19years) were studied. Improvement was noted in symptoms as well as urodynamic parameters in all groups. Maximal improvement of symptom score was with combination of drugs at 1year. In urodynamic studies, compliance, pressures, and capacity showed improvement, which was significant between the groups at both six months and 1year for bladder pressures and volume. Improvement in compliance though marked was not statistically significant. Best response was seen in group receiving both drugs. Gabapentin was better tolerated than oxybutynin. CONCLUSION: Gabapentin is a good alternative to oxybutynin for management of neurogenic bladder, both as monotherapy and as an add-on therapy. It has potential application in patients with inadequate response to anticholinergics. LEVEL OF EVIDENCE: prospective competitive treatment study - level II. PMID- 27680599 TI - Application of anchoring stitch prevents rectal prolapse in laparoscopic assisted anorectal pullthrough. AB - BACKGROUND: Rectal prolapse has been reported after laparoscopic assisted anorectal pullthrough in children with anorectal malformation. We report our clinical outcome and study the application of an anchoring stitch to tack the rectum to the presacral fascia and the occurrence of rectal prolapse. MATERIAL AND METHODS: A retrospective review of all children who had undergone laparoscopic assisted anorectal pullthrough for anorectal malformation from 2000 to 2015 was performed. Patients were divided into two groups (group I: with anchoring stitch, group II: without anchoring stitch). Outcome measures including rectal prolapse, soiling, voluntary bowel control, and constipation, and Kelly Score were analyzed. RESULTS: There were thirty-four patients (group I, n=20; group II, n=14) undergoing laparoscopic assisted anorectal pullthrough during the study period. The median follow up duration for group I and group II was 60months and 168months, respectively. All patients had stoma performed prior to the operation. Both groups consisted of patients with high type (30% vs 57%, p=0.12) and intermediate type (70% vs 43%, p=0.12) anorectal malformation. Seven (35%) patients in group I and 3 (21%) in group II had concomitant vertebral and spinal cord pathologies (p=0.408). The mean operative time was significantly shorter in group I (193+/-63min vs 242+/-49min, p=0.048). Rectal prolapse occurred less in group I, 4 (20%) vs 9 (64%) patients in group II and was statistically significant (p=0.008). Median time to development of rectal prolapse was 7months in group I and 5months in group II (p=0.767). Mucosectomy was performed in 15% of group I and 36% of group II (p=0.171). Soiling occurred less in group I (55% vs 79%, p=0.167). Voluntary bowel control (85% vs 93%, p=0.499) and constipation (55% vs 64%, p=0.601) were comparable in both groups. 75% in group I and 71% in group II achieved a Kelly score of 5 or above (p=0.823). CONCLUSIONS: Our study showed application of anchoring stitch reduces rectal prolapse and soiling in laparoscopic assisted anorectal pullthrough. Treatment Study-Level III. PMID- 27680600 TI - CT imaging for long-term functional outcome after spontaneous intracerebral haemorrhage: A 3-year follow-up study. AB - PRIMARY OBJECTIVE: To define the prognostic value of head computed tomography (CT) in patients suffering from SICH after 3 years of follow-up. RESEARCH DESIGN AND METHODS: Between January 2011 and May 2012, consecutive patients with SICH who underwent brain CT scans within the first 12 hours of presentation were prospectively included. Independent predictors of 30-day mortality and unfavourable functional outcome (modified Rankin Scale = 4-6 and Barthel Index <= 60) at 36 months were identified by univariable and multivariable regression analysis. MAIN OUTCOMES AND RESULTS: A total of 228 participants were identified. According to multivariable analysis, independent CT-related predictors for 30-day mortality were intraventricular haemorrhage [IVH] (OR = 2.42; p = 0.009), haematoma volume >= 30 cm3 (OR = 3.32; p = 0.006), the presence of midline shift (OR = 3.77; p = 0.004) and hydrocephalus (OR = 5.22; p = 0.001). Further, IVH (OR = 3.72, 95% CI = 1.16-11.8, p = 0.026), volume of haemorrhage >= 30 cm3 (OR = 3.96; 95% CI = 1.65-5.84; p = 0.015) and midline shift (OR = 6.58; 95% CI = 1.33 32.4; p = 0.021) had significant associations with an mRS >= 4 at 36 months. CONCLUSIONS: A favourable long-term functional outcome at 36 months and short term survival were less likely in patients with greater volume of haematoma, presence of IVH and midline displacement. PMID- 27680598 TI - Sustained delivery of vincristine inside an orthotopic mouse sarcoma model decreases tumor growth. AB - BACKGROUND: Sarcoma accounts for 20% of solid tumors in children. Surgery has significant morbidity. We hypothesized that delivering chemotherapy directly into tumors through sustained release silk systems could slow tumor growth. METHODS: Human Ewing sarcoma cells A673 were cultured with vincristine and doxorubicin to determine half maximal inhibitory concentration (IC50). Cells were injected into mouse hind leg to create orthotopic tumors. Tumor volumes were measured using ultrasound. When volume reached >250mm3, interventions included: implantation of drug-free silk foam (Control-F), doxorubicin 400MUg foam (Dox400-F), vincristine 50MUg foam (Vin50-F), drug-free silk gel (Control-G), vincristine 50MUg gel (Vin50-G), or single dose intravenous vincristine 50MUg (Vin50-IV). End-point was volume>1000mm3. Kaplan Meier and ANOVA were used. RESULTS: IC50 for vincristine and doxorubicin was 0.5ng/mL and 200ng/mL, respectively. There was no difference between Dox400-F [6+/-1days to end point (DTEP)] and Control-F (5+/-1.3 DTEP). Vin50-F (12.4+/-3.5 DTEP) had slower growth compared to Control-F (p<0.001), and there was no difference between Vin50-F and Vin50-IV (14+/-0 DTEP). Growth was slowest with Vin50-G, 28+/-10.3 DTEP compared to all other treatment groups (p<0.05). CONCLUSION: Sustained delivery of vincristine inside the sarcoma tumor with silk gel decreased tumor growth. Applying this intratumoral treatment strategy may potentially decrease the extent of surgical excision. PMID- 27680601 TI - Predicting 30-Day Readmission or Death in Patients With Heart Failure: Looking Beyond the C Statistic. PMID- 27680602 TI - The Longitudinal Relation Between Accumulation of Adverse Life Events and Body Mass Index From Early Adolescence to Young Adulthood. AB - OBJECTIVE: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been investigated to date. METHODS: Data are from 2188 children participating at T1 (10-12 years), T3 (14-18 years), and/or T5 (21-23 years) of the prospective Tracking Adolescents' Individual Lives Survey cohort study. Adverse events before T1 and between T1, T3, and T5 were measured with a parent interview at T1 and a semistructured interview (Event History Calendar) with the adolescent at T3 and T5. An adverse events score was calculated per wave. Body mass index z-scores were determined from objectively measured height and weight using the LMS (skewness, median, and coefficient of variation) reference curves of the International Obesity Task Force for children 18 years or younger. Data were analyzed using a modified bivariate autoregressive cross-lagged structural equation model. RESULTS: Adverse events before T1 and between T3 and T5 were related to BMI at T5 (beta = 0.06, p = .001 and beta = 0.04, p = .04, respectively). Specifically, health events before T1 were associated with a higher BMI at T5, and events related to relationships and victimhood events between T3 and T5 were associated with a lower BMI at T5. CONCLUSIONS: Adverse relationship and victimhood events in their recent past were related to a lower BMI in young adults, whereas adverse health events during childhood were related to a higher BMI in young adults. No relationships were found between adverse life events with BMI in children and adolescents. PMID- 27680603 TI - Clinical phenotype and current diagnostic criteria for primary ciliary dyskinesia. AB - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, mostly autosomal recessive disorder of motile cilia, characterized by chronic lung disease, rhinosinusitis, hearing impairment, and subfertility. PCD is still often missed or diagnosed late since symptoms overlap with common respiratory complaints, but should be considered if one or more of the cardinal clues are present. Areas covered: We provide an overview on clinical presentations of PCD and clues for when to consider PCD, these include unexplained neonatal respiratory distress, persistent rhinitis from the first days of life, situs anomalies, or otorrhoea following tympanostomy tube insertion. Diagnosis is on the basis of clinical suspicion, and an algorithm of nasal nitric oxide, ciliary beat pattern and frequency, transmission electron microscopy, immunofluorescence of ciliary proteins and genetic studies. However, there is no one gold-standard test as yet. We reviewed the current literature based on PubMed and Ovid databases literature search. Expert commentary: There is a need for increased awareness about PCD beyond specialist respiratory clinicians and a need for standardization of PCD diagnostics internationally. Early diagnosis means that inappropriate treatment based on misdiagnosed conditions can be avoided, and the onset of bronchiectasis may be delayed. PMID- 27680604 TI - CK7 Immunohistochemistry as a Predictor of CIN1 Progression: A Retrospective Study of Patients From the Quadrivalent HPV Vaccine Trials. AB - Cervical high-grade squamous intraepithelial lesion (CIN2-3) is thought to arise from a distinct population of cells at the squamocolumnar junction (SCJ). Immunohistochemical (IHC) biomarkers that characterize the SCJ phenotype, including CK7, have been proposed as tools to separate the subset of low-grade squamous intraepithelial lesions (LSILs) (CIN1) that will progress to high-grade squamous intraepithelial lesion from the majority of cases, which will resolve without further intervention. We conducted a retrospective study of CK7 IHC on adjudicated CIN1 tissue from women in the placebo arm of the quadrivalent human papillomavirus (HPV) vaccine trials. Tissue sections were stained with CK7 IHC and scored as negative, patchy, gradation (ie, top-down), or full-thickness pattern. Results were assessed for the prediction of future diagnosis of CIN2 3/AIS (eg, CIN2+ progression) along with p16 IHC, antecedent high-grade cytology, and HPV16 status. A total of 517 patients with CIN1 biopsies and complete data were identified, 12% of whom showed CIN2+ progression on follow-up. Full thickness CK7 staining showed the highest correlation with CIN2+ progression (odds ratio [OR] 2.8, P=0.021) relative to the other risk factors (HPV16: OR 2.0, P=0.035; antecedent high-grade cytology: OR 2.2, P=0.028; p16 IHC: OR 1.5, P=0.16). Inclusion of the gradation/"top-down" CK7 pattern resulted in a less robust association with progression (CIN2+: OR 2.0, P=0.028; CIN3+: OR 1.3, P=0.74). Interobserver variability ranged from slight to substantial and was not contingent on gynecologic pathology training experience (kappa=0.7078 for negative/patchy vs. gradation/full thickness; kappa=0.5672 for negative/patchy/gradation vs. full thickness). These data support the theory that SCJ-derived LSILs are precursors to a potentially aggressive subset of cervical SILs and that CK7 staining may inform risk stratification for LSIL (CIN1). However, clinical utility is significantly tempered by the relatively low amplitude of the risk increase, interpretative variability, and limitations of colposcopic sampling. PMID- 27680605 TI - Oncogene Status of an Interdigitating Dendritic Cell Sarcoma: Recurrent Mutations in NF1, TP53, and ARID2 Shared With Melanoma. PMID- 27680606 TI - Monoclonal antibody therapy for neuromyelitis optica spectrum disorder: current and future. AB - Monoclonal-antibody has been used for patients with autoimmune disorders for several years, and efficacy and safety were appreciated for these patients. Neuromyelitis optica specturm disorder (NMOSD) has been defined as an autoimmune demyelination disorder of the central nervous system (CNS) with a course of relapse-remission. Treatment of prevention is important for patients with NMOSD because of the increased disability after several attacks. Multiple factors were involved in the pathogenesis of NMOSD. Currently, targeting specific factor was favored in the research into the treatment for NMOSD. Previous studies reported the efficacy and tolerance in NMOSD for drugs such as rituximab, tocilizumab, and eculizumab. The aim of this article is to review the current monoclonal therapies for NMOSD patients, and also future alternative options. PMID- 27680607 TI - What to Do When the Managed Care Firm Says No. PMID- 27680608 TI - Comparison of the effects of PRP and hyaluronic acid in promoting peripheral nerve regeneration An experimental study with vascular conduit model in rats'. AB - AIM: Peripheral nerve defects generally occur due to mechanical, chemical, thermal and pathologic causes and the reconstruction is still a challenging problem. In the present study, we aimed to compare the effects of platelet rich plasma (PRP) that has high levels of growth factors and hyaluronic acid (HA) that is known to have positive effects on nerve regeneration by decreasing scar formation in a rat model where they were injected through allogeneic aorta graft in peripheral nerve defects using histopathologic and functional methods. MATERIAL AND METHODS: The study involved 20 Wistar Albino male rats that weighed 200 to 250 grams and aged about 1 year old. Of the rats, two were used as donor for PRP and aorta graft harvest. Three random groups of 6 rats were composed. In all of the groups, the left sciatic nerves were used and 1 cm of defects were created. The right sciatic nerves were used as control groups. Group 1 was the group repaired with autograft, Group 2 was the group repaired with HA injected through aorta graft and Group 3 was the group repaired with PRP injected through aorta graft. The findings were evaluated in terms of functional (electromyography and walk test analysis) and histopathologic parameters at 12 weeks. RESULTS: In all of the groups varying degrees of axonal regeneration was observed. Group 1 was the closest group to the control group showing highest rate of nerve regeneration followed by Group 3 where PRP was injected through aorta graft and group 2 where ha was used respectively. CONCLUSION: The study demonstrates that PRP enhances peripheral nerve regeneration more than HA when used in a vascular conduit model. KEY WORDS: Hyaluronic acid, Peripheral nerve regeneration, PRP. PMID- 27680609 TI - Bifurcation intervention with a two-stent strategy: can one size fit all? PMID- 27680610 TI - A large right ventricular mass in a 42-year-old female marathon runner. PMID- 27680611 TI - Three-dimensional cinematric volume rendering technique: a novel photon-based post-processing technique for reverse right internal mammary artery/right coronary artery bypass visualization. PMID- 27680613 TI - Helping to adjust: an holistic approach to stoma care. AB - The aim of this Learning Unit is to increase your knowledge about the psychological implications of stoma formation and to increase your understanding of the process of psychological adaptation, in order that you can offer more sensitive care. PMID- 27680614 TI - ? AB - Serious questions need to be asked about the independence of the UK Central Council following allegations that it may have bowed to government pressure to suppress a damning report into nursing homes until after the European elections because its findings may be politically sensitive. PMID- 27680615 TI - Ralph investigation to report this week. AB - The findings of an investigation into UKCC Registrar Colin Ralph's role in the appointment of an administrative post at UKCC headquarters are expected at the end of this week. PMID- 27680616 TI - UKCC accused of complicity in cover-up. AB - The UKCC is at the centre of further controversy concerning allegations that it bowed to Government pressure not to release a damning report into nursing homes until after the European Elections. PMID- 27680617 TI - Widespread discrimination faced by black nurses. AB - Evidence of widespread discrimination against ethnic minority applicants to nurse training was revealed in the Commons last week. PMID- 27680618 TI - Staff side reject performance related pay. AB - Management attempts to introduce performance related pay for nurses and other NHS professionals were rebutted again by staff side last week. PMID- 27680621 TI - ? AB - We' ll meet again: Fifty years after they met while saving the lives of D-Day casualties in Normandy, 'Flying Nightingales' Myra Jones (nee Roberts), left, and Edna Morris (nee Birbeck) shared memories of the battle that turned the war, at the Imperial War Museum last week ? Special features starting on p16. PMID- 27680619 TI - Anorexia nurse is suspended. AB - A student midwife who had anorexia in 1984 is claiming the post-Allitt witch-hunt has led to her suspension just weeks before her final exams. PMID- 27680622 TI - Nurses can offer reassurance in 'killer bug' scare. AB - Infection control nurses are. having to play a vital role reassuring the public after the outbreak of the so-called 'killer bug', necrotising fasciitis. PMID- 27680623 TI - ? AB - Devil food: The grim biker' joined Baby Milk Action demonstrators outside Nestle s UK headquarters in Croydon last week. They were protesting against what they claim are aggressive promotion strategies to sell baby milk throughout the world. A second protest is scheduled for Nestle s AGM in Switzerland. PMID- 27680624 TI - Too few places for Project 2000 child nursing students. AB - Difficulties in finding community placements for students on the Project 2000 child nursing course means there is no common currency in their diplomas, according to a report published last week. PMID- 27680625 TI - Hidden cameras to help prove child abuse. AB - Covert video surveillance of parents suspected of smothering or abusing their children has received the qualified approval of the Royal College of Nursing. PMID- 27680626 TI - Power-mad nurses get personal with patients. AB - Inappropriate relationships between nurses and patients usually start because the nurse is 'besotted with power' and colleagues are reluctant to blow the whistle on the relationship, UKCC Assistant Registrar Tariq Hussain said last week. PMID- 27680627 TI - 'No fee' legal firm swamped by opt-out nurses. AB - A Bristol firm of solicitors offering a 'no win, no fee' ser- I vice to nurses who have lost money on leaving the NHS pensions scheme has been I flooded with hundreds of calls. PMID- 27680628 TI - Doh go slow on mental health. AB - Fears that the recommendations of the mental health nursing review, published earlier this year, would not see the light of day were dismissed by the Chair of the review team last week. PMID- 27680631 TI - Unions face set-back over injuries Bill. AB - A bid by trade unions to stop the Government from scrapping the Criminal Injuries Compensation Board was lost in the High Court last week. PMID- 27680630 TI - UKCC warned that supernumerary promises are being broken over 'tightrope' students. AB - Government promises to allow nursing students to be supernumerary are not being kept, UK Central Council officers have been warned. PMID- 27680633 TI - Campaign to stop bullies at work. AB - A campaign to combat bullying in the workplace was launched by the union MSF last week in response to rising numbers of complaints. PMID- 27680634 TI - Package aimed at pregnant smokers. AB - Concerns over the ability of health professionals to help pregnant women who smoke are to be tackled with the release of a new training package. PMID- 27680632 TI - Nurse prescribing biased to help fundholders only. AB - Labour MP Tessa Jowell has accused the Government of using nurse prescribing as a ploy to promote GP fundholding. PMID- 27680636 TI - Poor targeting blamed as routine health checks fail the equality test. AB - Socially deprived people and those with unhealthy lifestyles are less likely to attend a routine health check, new research has shown. PMID- 27680637 TI - Ambu Cardio Pump found useful in resuscitation. AB - Active compression-decompression (ACD) resuscitation appears to be more effective than the standard method for victims of cardiac arrest outside hospital. American researchers undertook a prospective randomised parallel group study comparing standard CPR with ACD delivered by Ambu Cardio Pump. Resuscitation was undertaken by emergency services personnel trained in the pump's use. PMID- 27680635 TI - Parents ignoring sunburn warnings. AB - British parents are not being vigilant enough in protecting their children from the sun, says a survey published last week. PMID- 27680638 TI - Garlic may soon rival commercial antibiotics. AB - Garlic might have a more important use than just spicing up your food. American researchers believe the substance which gives garlic its characteristic smell, allicin, might have some potency against bacteria, including those which are resistant to conventional antibiotics. PMID- 27680640 TI - New' therapy shown to prolong life in colon cancer. AB - Adjuvant therapy with a monoclonal antibody extends the life of and prolongs remission in people with Dukes' stage C colorectal cancer. PMID- 27680639 TI - Why smear uptake varies. AB - Over half the variation in cervical smear uptake rates can be explained by patient and general practice variables, London researchers report. PMID- 27680642 TI - One nurse's war. AB - In the summer of 1939, Florence Simes was intending to use her valuable nursing and midwifery qualifications as a passport to seethe world. Plans were under way for her to join a P&O passenger liner as a ship's nurse. PMID- 27680641 TI - Being there... AB - I sat in silence in my battle dress, tin hat, a Red Cross armband prominently on my left arm. Straight ahead, jeeps, trucks and ambulances could be seen mounting the distant hill. In spire of the familiar sound of the convoy making its progress, it seemed incredibly still, almost unreal. The memorable day was June 5, 1944 and I was setting out on what was to be the greatest adventure of my life. PMID- 27680643 TI - Unrealistic view of coping with cancer. AB - I read with interest the article by Lucy Burgess, 'Facing the reality of head and neck cancer' (Clinical, May 4). PMID- 27680644 TI - NDUs side-swiped by punchy editorial. AB - I take exception to the final paragraph in an otherwise useful and appropriately questioning editorial on clinical supervision (May 18). PMID- 27680645 TI - Quarry digging reveals injustice. AB - Many of us have been disturbed by the TV programme Here and Now which showed the giant new building, Quarry House in Leeds, erected at a cost of L55 million for the use of top NHS administrators. PMID- 27680646 TI - Joy Reilly. AB - The sudden death on May 2 of RCN member Joy Reilly after a short illness has left her family, friends and colleagues devastated. Joy's death at the early age of 57 will leave a void in the RCN in Northern Ireland and in particular the South and East Belfast Branch. She played a key role in developing the RCN's effectiveness, especially as a Northern Ireland Board member and previously through the Psychiatric Society. She retired from her post as ward sister in 'Shimna' Knockbraken Healthcare Park (formerly Purdysburn Hospital) only last autumn. She will be sadly missed by her patients, colleagues and friends in the health service and by the many friends she made on the mainland during the times she attended RRB and Congress. PMID- 27680647 TI - Brain drain gains fame. AB - I agree so strongly with the observations made by Teresa Burgoyne in 'The brain drain' (Viewpoint, May 18). PMID- 27680648 TI - More research please on ethnicity and diet. AB - I would like to clarify some elements of your report of my presentation at the Florence Nightingale scholarships (Newsfile, April 28). PMID- 27680649 TI - Information exchange. PMID- 27680650 TI - Reunions. AB - September 17 is the date for a 20th anniversary reunion for all nurses who commenced training at The Royal Free Hospital in September 1974. It will be held in London and anyone wanting details can contact Jacky Ashby-Swain (nee Swain) on 0408 30455. PMID- 27680651 TI - Mattresses: springing to the defence. AB - We would like to correct any misapprehensions arising from the Tissue Viability news item, 'Alternating pressure overlays give best results in clinical trials' (May 18). PMID- 27680652 TI - D-Day revisited. PMID- 27680653 TI - Gossip. AB - The big news this week is that prefabricated buildings are no longer viewed as a poor substitute for traditional buildings. That's what it says here, anyway. In a press release headed Future looking bright for prefabricated building industry', Rovacabin - 'leading suppliers of modular and portable buildings' - says average turnover in the prefab, building industry rose by 20 per cent in the second half of 1993. PMID- 27680654 TI - Gentle medicine Gentle medicine A Smyth Thorsons 616pp L10.99 0-7225-2769-1. AB - The simple health programme that I follow has helped me to enjoy good health for many I years. As I approach my fiftieth birthday, I recommend the benefits of being a teetotaller and non- smoker, having sufficient sleep, eating a balanced diet, taking enough exercise, trying not to worry and enjoying creative hobbies. PMID- 27680656 TI - Oncological nursing, 2nd edition Oncological nursing, 2nd edition J H Eriksson Springhouse 234pp L11.50 0-87434-613-4. AB - Oncological Nursing. 2nd edition is part of the Springhouse notes series of study and learning guides. It aims to provide all the information needed to review the specialty of oncology nursing, covering the core topics found in all major textbooks on the subject and highlighting key points, enabling the student to review critical material rapidly. A glossary of frequently used or misunderstood terms is provided. PMID- 27680657 TI - Listings. AB - Nursing Standard regrets that it is no longer able to take listings over the telephone because of unprecedented demand. Readers are reminded that the listings section is for the use of charitable and professional organisations, unions and health authorities to publicise forthcoming events. Listings should contain all relevant details and be posted or faxed to Susan B/oodworth, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX. Pax: 081-423 3867. PMID- 27680658 TI - Pacing From the Right Ventricular Septum and Development of New Atrial Fibrillation in Paced Patients With Atrioventricular Block and Preserved Left Ventricular Function. AB - BACKGROUND: Whether pacing from the right ventricular (RV) septum improves prognosis is unclear. Furthermore, the clinical characteristics of patients who develop atrial fibrillation (AF) and cardiovascular events during long-term RV septal pacing have not been described.Methods and Results:We retrospectively evaluated the incidence of AF and cardiovascular events, including cardiac death, heart failure requiring hospitalization, or stroke, for a median of 4.0 years in 123 recipients of dual-chamber pacemakers implanted for atrioventricular block with preserved left ventricular function, who were free from AF before device implantation. AF developed in 30 patients (24%), and multivariable analysis suggested that the cumulative percentage of RV pacing was the only independent predictor of newly developed AF (hazard ratio: 1.19 for each 10% increment; 95% confidence interval: 1.04-1.41; P=0.01). Furthermore, older age, newly developed AF and a paced QRS duration >=155 ms at pacemaker implantation were significant predictors of cardiovascular events. CONCLUSIONS: RV septum pacing may induce AF in up to one-quarter of patients paced for atrioventricular block, according to the frequency of pacing. More importantly, in such patients, AF induced by RV pacing and a paced QRS duration >=155 ms at pacemaker implantation are significantly associated with poor prognosis. Therefore, we recommend pacing from sites producing a paced QRS duration <155 ms and avoiding unnecessary RV pacing. (Circ J 2016; 80: 2302-2309). PMID- 27680659 TI - Impact of Gender Binarism on Hijras' Life Course and Their Access to Fundamental Human Rights in Pakistan. AB - This study adds to the growing body of knowledge on gender nonconformity aspects of heteronormativity by examining its impact on the life course of hijras and their access to fundamental human rights in Pakistan. Drawing on 50 semistructured interviews conducted in two sites, the findings suggest that the participants' lived experiences associated with gender nonconformity significantly influenced the direction of their life course and their ability to have access to human rights. These experiences spanned from childhood to elderhood across a wide range of settings, such as family, school, guru dera (residence headed by a hijra guru), workplace, and interactions with authorities. The participants' human rights were not recognized, resulting in abuse, social stigma, discrimination against them, and their exclusion from mainstream society. Finally, implications are drawn for public policy and future research on third gender concerns in Pakistan and elsewhere. PMID- 27680660 TI - Why Are There Developmental Stages in Language Learning? A Developmental Robotics Model of Language Development. AB - Most theories of learning would predict a gradual acquisition and refinement of skills as learning progresses, and while some highlight exponential growth, this fails to explain why natural cognitive development typically progresses in stages. Models that do span multiple developmental stages typically have parameters to "switch" between stages. We argue that by taking an embodied view, the interaction between learning mechanisms, the resulting behavior of the agent, and the opportunities for learning that the environment provides can account for the stage-wise development of cognitive abilities. We summarize work relevant to this hypothesis and suggest two simple mechanisms that account for some developmental transitions: neural readiness focuses on changes in the neural substrate resulting from ongoing learning, and perceptual readiness focuses on the perceptual requirements for learning new tasks. Previous work has demonstrated these mechanisms in replications of a wide variety of infant language experiments, spanning multiple developmental stages. Here we piece this work together as a single model of ongoing learning with no parameter changes at all. The model, an instance of the Epigenetic Robotics Architecture (Morse et al 2010) embodied on the iCub humanoid robot, exhibits ongoing multi-stage development while learning pre-linguistic and then basic language skills. PMID- 27680661 TI - Experimental evidence of pollination in marine flowers by invertebrate fauna. AB - Pollen transport by water-flow (hydrophily) is a typical, and almost exclusive, adaptation of plants to life in the marine environment. It is thought that, unlike terrestrial environments, animals are not involved in pollination in the sea. The male flowers of the tropical marine angiosperm Thalassia testudinum open up and release pollen in mucilage at night when invertebrate fauna is active. Here we present experimental evidence that, in the absence of water-flow, these invertebrates visit the flowers, carry and transfer mucilage mass with embedded pollen from the male flowers to the stigmas of the female flowers. Pollen tubes are formed on the stigmas, indicating that pollination is successful. Thus, T. testudinum has mixed abiotic-biotic pollination. We propose a zoobenthophilous pollination syndrome (pollen transfer in the benthic zone by invertebrate animals) which shares many characteristics with hydrophily, but flowers are expected to open-up during the night. PMID- 27680662 TI - Transcriptome landscape of perennial wild Cicer microphyllum uncovers functionally relevant molecular tags regulating agronomic traits in chickpea. AB - The RNA-sequencing followed by de-novo transcriptome assembly identified 11621 genes differentially xpressed in roots vs. shoots of a wild perennial Cicer microphyllum. Comparative analysis of transcriptomes between microphyllum and cultivated desi cv. ICC4958 detected 12772 including 3242 root- and 1639 shoot specific microphyllum genes with 85% expression validation success rate. Transcriptional reprogramming of microphyllum root-specific genes implicates their possible role in regulating differential natural adaptive characteristics between wild and cultivated chickpea. The transcript-derived 5698 including 282 in-silico polymorphic SSR and 127038 SNP markers annotated at a genome-wide scale exhibited high amplification and polymorphic potential among cultivated (desi and kabuli) and wild accessions suggesting their utility in chickpea genomics assisted breeding applications. The functional significance of markers was assessed based on their localization in non-synonymous coding and regulatory regions of microphyllum root-specific genes differentially expressed predominantly in ICC 4958 roots under drought stress. A high-density 490 genic SSR- and SNP markers-anchored genetic linkage map identified six major QTLs regulating drought tolerance-related traits, yield per plant and harvest-index in chickpea. The integration of high-resolution QTL mapping with comparative transcriptome profiling delineated five microphyllum root-specific genes with non synonymous and regulatory SNPs governing drought-responsive yield traits. Multiple potential key regulators and functionally relevant molecular tags delineated can drive translational research and drought tolerance-mediated chickpea genetic enhancement. PMID- 27680664 TI - Left Atrial Appendage Closure Under Intracardiac Echocardiographic Guidance: Feasibility and Comparison With Transesophageal Echocardiography. AB - BACKGROUND: Transcatheter left atrial appendage closure is an alternative therapy for stroke prevention in atrial fibrillation patients. These procedures are currently guided with transesophageal echocardiography and fluoroscopy in most centers. As intracardiac echocardiography (ICE) is commonly used in other catheter-based procedures, we sought to determine the safety and effectiveness of intracardiac echocardiography-guided left atrial appendage closure with the Watchman device. METHODS AND RESULTS: A total of 27 patients (11 males, 77.0+/ 8.5 years) with atrial fibrillation receiving Watchman left atrial appendage closure under intracardiac echocardiography guidance at a single center were investigated. All patients were implanted successfully. There were no major procedural complications. The overall procedure-related complication rate was 14.8%, mainly due to access site hematoma. Transesophageal echocardiography demonstrated successful closure of the left atrial appendage in all patients at 45 days after device implant. CONCLUSIONS: Transcatheter left atrial appendage closure with intracardiac echocardiography guidance is safe and feasible. PMID- 27680665 TI - Angina and Future Cardiovascular Events in Stable Patients With Coronary Artery Disease: Insights From the Reduction of Atherothrombosis for Continued Health (REACH) Registry. AB - BACKGROUND: The extent to which angina is associated with future cardiovascular events in patients with coronary artery disease has long been debated. METHODS AND RESULTS: Included were outpatients with established coronary artery disease who were enrolled in the REACH registry and were followed for 4 years. Angina at baseline was defined as necessitating episodic or permanent antianginal treatment. The primary end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included heart failure, cardiovascular hospitalizations, and coronary revascularization. The independent association between angina and first/total events was examined using Cox and logistic regression models. Out of 26 159 patients with established coronary artery disease, 13 619 (52%) had angina at baseline. Compared with patients without angina, patients with angina were more likely to be older, female, and had more heart failure and polyvascular disease (P<0.001 for each). Compared with patients without angina, patients with angina had higher rates of first primary end-point event (14.2% versus 16.3%, unadjusted hazard ratio 1.19, CI 1.11-1.27, P<0.001; adjusted hazard ratio 1.06, CI 0.99-1.14, P=0.11), and total primary end point events (adjusted risk ratio 1.08, CI 1.01-1.16, P=0.03). Patients with angina were at increased risk for heart failure (adjusted odds ratio 1.17, CI 1.06-1.28, P=0.002), cardiovascular hospitalizations (adjusted odds ratio 1.29, CI 1.21-1.38, P<0.001), and coronary revascularization (adjusted odds ratio 1.23, CI 1.13-1.34, P<0.001). CONCLUSIONS: Patients with stable coronary artery disease and angina have higher rates of future cardiovascular events compared with patients without angina. After adjustment, angina was only weakly associated with cardiovascular death, myocardial infarction, or stroke, but significantly associated with heart failure, cardiovascular hospitalization, and coronary revascularization. PMID- 27680663 TI - Dynamic Resistance Training as Stand-Alone Antihypertensive Lifestyle Therapy: A Meta-Analysis. AB - BACKGROUND: Aerobic exercise (AE) is recommended as first-line antihypertensive lifestyle therapy based on strong evidence showing that it lowers blood pressure (BP) 5 to 7 mm Hg among adults with hypertension. Because of weaker evidence showing that dynamic resistance training (RT) reduces BP 2 to 3 mm Hg among adults with hypertension, it is recommended as adjuvant lifestyle therapy to AE training. Yet, existing evidence suggests that dynamic RT can lower BP as much or more than AE. METHODS AND RESULTS: We meta-analyzed 64 controlled studies (71 interventions) to determine the efficacy of dynamic RT as stand-alone antihypertensive therapy. Participants (N=2344) were white (57%), middle-aged (47.2+/-19.0 years), and overweight (26.8+/-3.4 kg/m(2)) adults with prehypertension (126.7+/-10.3/76.8+/-8.7 mm Hg); 15% were on antihypertensive medication. Overall, moderate-intensity dynamic RT was performed 2.8+/-0.6 days/week for 14.4+/-7.9 weeks and elicited small-to-moderate reductions in systolic BP (SBP; d+=-0.31; 95% CIs, -0.43, -0.19; -3.0 mm Hg) and diastolic BP (DBP; d+=-0.30; 95% CIs, -0.38, -0.18; -2.1 mm Hg) compared to controls (Ps<0.001). Greater BP reductions occurred among samples with higher resting SBP/DBP: ~6/5 mm Hg for hypertension, ~3/3 mm Hg for prehypertension, and ~0/1 mm Hg for normal BP (Ps<0.023). Furthermore, nonwhite samples with hypertension experienced BP reductions that were approximately twice the magnitude of those previously reported following AE training (-14.3 mm Hg [95% CIs, -19.0, -9.4]/ 10.3 mm Hg [95% CIs, -14.5, -6.2]). CONCLUSIONS: Our results indicate that for nonwhite adult samples with hypertension, dynamic RT may elicit BP reductions that are comparable to or greater than those reportedly achieved with AE training. Dynamic RT should be further investigated as a viable stand-alone therapeutic exercise option for adult populations with high BP. PMID- 27680668 TI - Sialidase Unmasks Mucin Domain Epitopes of Lubricin. AB - Lubricin is a secreted, mucin-like glycoprotein and proteoglycan abundant in synovial fluid that provides boundary lubrication and prevents cell adhesion in synovial joints. The antilubricin S6.79 monoclonal antibody recognizes an O linked glycopeptide epitope in lubricin's mucin domain. The central, long mucin domain of lubricin is extensively O-glycosylated with Gal(beta1-3)GalNAc-O Ser/Thr, and about two thirds of the O-glycosylated sites are capped with sialic acid. Our aim was to determine whether removal of sialic acid by sialidase could improve the detection of lubricin in a number of human tissues using the S6.79 monoclonal antibody. Sialidase treatment caused a dramatic increase in antibody reactivity in human pericardium, splenic capsule and trabeculae, plasma, serum, eye sleep extract, and liver sinusoids. Sialidase had minimal effect on S6.79 antibody reactivity with lubricin in synovial fluid and synovial tissue. These observations suggest that the origin of lubricin in blood may be different from that in synovial fluid and that desialylation of lubricin is essential for unmasking epitopes within the mucin domain. PMID- 27680666 TI - Caveolin 1 Modulates Aldosterone-Mediated Pathways of Glucose and Lipid Homeostasis. AB - BACKGROUND: Overactivation of the aldosterone and mineralocorticoid receptor (MR) pathway is associated with hyperglycemia and dyslipidemia. Caveolin 1 (cav-1) is involved in glucose/lipid homeostasis and may modulate MR signaling. We investigated the interplay between cav-1 and aldosterone signaling in modulating insulin resistance and dyslipidemia in cav-1-null mice and humans with a prevalent variant in the CAV1 gene. METHODS AND RESULTS: In mouse studies, cav-1 knockout mice exhibited higher levels of homeostatic model assessment of insulin resistance, cholesterol, and resistin and lower ratios of high- to low-density lipoprotein (all P<0.001 versus wild type). Moreover, cav-1 knockout mice displayed hypertriglyceridemia and higher mRNA levels for resistin, retinol binding protein 4, NADPH oxidase 4, and aldose reductase in liver and/or fat tissues. MR blockade with eplerenone significantly decreased glycemia (P<0.01), total cholesterol (P<0.05), resistin (P<0.05), and described enzymes, with no effect on insulin or triglycerides. In the human study, we analyzed the CAV1 gene polymorphism rs926198 in 556 white participants; 58% were minor allele carriers and displayed higher odds of insulin resistance (odds ratio 2.26 [95% CI 1.40 3.64]) and low high-density lipoprotein (odds ratio 1.54 [95% CI 1.01-3.37]). Aldosterone levels correlated with higher homeostatic model assessment of insulin resistance and resistin and lower high-density lipoprotein only in minor allele carriers. CAV1 gene expression quantitative trait loci data revealed lower cav-1 expression in adipose tissues by the rs926198 minor allele. CONCLUSIONS: Our findings in mice and humans suggested that decreased cav-1 expression may activate the effect of aldosterone/MR signaling on several pathways of glycemia, dyslipidemia, and resistin. In contrast, hyperinsulinemia and hypertriglyceridemia are likely mediated by MR-independent mechanisms. Future human studies will elucidate the clinical relevance of MR blockade in patients with genotype-mediated cav-1 deficiency. PMID- 27680667 TI - Immunophenotyping of Rabbit Testicular Germ and Sertoli Cells Across Maturational Stages. AB - During testicular maturation, both Sertoli cells (SCs) and germ cells (GCs) switch from an immature to a mature immunophenotype. The reexpression of markers of immaturity in adults has been reported in cancer and in other testicular pathologies, in men as well as in animal species. Naturally affected with testicular cancer, rabbits have long been used in human reproductive research, but reports on the expression of testicular cell markers in this species are few and data about the immunophenotype of normal postnatal SCs and GCs are lacking. The aim of this study was to investigate the immunophenotype of SCs and GCs in the rabbit, from neonatal to adult age, using the antibodies anti-Mullerian hormone (AMH), vimentin (VIM), CKAE1/AE3 (cytokeratins [CKs]), desmin (DES), inhibin alpha (INH-alpha), placental alkaline phosphatase (PLAP), and periodic acid-Schiff (PAS) staining. In SCs, VIM was constantly expressed, and AMH and CKs expression was limited to neonatal and prepubertal age, whereas DES, INH-alpha, PLAP, and PAS were constantly negative. GCs were negatively stained for PLAP, PAS, and for the other markers. Results revealed analogies with human testicular immunophenotype, suggesting that rabbits could represent a potential experimental model for the study of human testicular pathology. PMID- 27680671 TI - Survival and failure modes: platform-switching for internal and external hexagon cemented fixed dental prostheses. AB - This study evaluated the probability of survival (reliability) of platform switched fixed dental prostheses (FDPs) cemented on different implant-abutment connection designs. Eighty-four-three-unit FDPs (molar pontic) were cemented on abutments connected to two implants of external or internal hexagon connection. Four groups (n = 21 each) were established: external hexagon connection and regular platform (ERC); external hexagon connection and switched platform (ESC); internal hexagon and regular platform (IRC); and internal hexagon and switched platform (ISC). Prostheses were subjected to step-stress accelerated life testing in water. Weibull curves and probability of survival for a mission of 100,000 cycles at 400 N (two-sided 90% CI) were calculated. The beta values of 0.22, 0.48, 0.50, and 1.25 for groups ERC, ESC, IRC, and ISC, respectively, indicated a limited role of fatigue in damage accumulation, except for group ISC. Survival decreased for both platform-switched groups (ESC: 74%, and ISC: 59%) compared with the regular matching platform counterparts (ERC: 95%, and IRC: 98%). Characteristic strength was higher only for ERC compared with ESC, but not different between internal connections. Failures chiefly involved the abutment screw. Platform switching decreased the probability of survival of FDPs on both external and internal connections. The absence in loss of characteristic strength observed in internal hexagon connections favor their use compared with platform switched external hexagon connections. PMID- 27680669 TI - Nucleolar Reorganization Upon Site-Specific Double-Strand Break Induction. AB - DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment. Here, we directed formation of double-strand breaks in rRNA genes with I- PpoI endonuclease, and we studied nucleolar morphology, DDR, and chromatin modifications. We observed a pronounced formation of I- PpoI-induced nucleolar caps, positive on BRCA1, NBS1, MDC1, gammaH2AX, and UBF1 proteins. We showed interaction of nucleolar protein TCOF1 with HDAC1 and TCOF1 with CARM1 after DNA injury. Moreover, H3R17me2a modification mediated by CARM1 was found in I- PpoI-induced nucleolar caps. Finally, we report that heterochromatin protein 1 is not involved in DNA repair of nucleolar caps. PMID- 27680670 TI - Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio ( Devario aequipinnatus) and Zebrafish ( Danio rerio) Hearts. AB - Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish ( Danio rerio) and giant danio ( Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins-wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)-in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins' ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID- 27680672 TI - Hedgehogs and Mustelid Species: Major Carriers of Pathogenic Leptospira, a Survey in 28 Animal Species in France (20122015). AB - Human leptospirosis is a zoonotic and potentially fatal disease that has increasingly been reported in both developing and developed countries, including France. However, our understanding of the basic aspects of the epidemiology of this disease, including the source of Leptospira serogroup Australis infections in humans and domestic animals, remains incomplete. We investigated the genetic diversity of Leptospira in 28 species of wildlife other than rats using variable number tandem repeat (VNTR) and multispacer sequence typing (MST). The DNA of pathogenic Leptospira was detected in the kidney tissues of 201 individuals out of 3,738 tested individuals. A wide diversity, including 50 VNTR profiles and 8 MST profiles, was observed. Hedgehogs and mustelid species had the highest risk of being infected (logistic regression, OR = 66.8, CI95% = 30.9-144 and OR = 16.7, CI95% = 8.7-31.8, respectively). Almost all genetic profiles obtained from the hedgehogs were related to Leptospira interrogans Australis, suggesting the latter as a host-adapted bacterium, whereas mustelid species were infected by various genotypes, suggesting their interaction with Leptospira was different. By providing an inventory of the circulating strains of Leptospira and by pointing to hedgehogs as a potential reservoir of L. interrogans Australis, our study advances current knowledge on Leptospira animal carriers, and this information could serve to enhance epidemiological investigations in the future. PMID- 27680674 TI - Physical and biochemical changes in sludge upon Tubifex tubifex predation. AB - Worm predation (WP) on activated sludge leads to increased sludge degradation rates, irrespective of the type of worm used or reactor conditions employed. However, the cause of the increased sludge degradation rates remains unknown. This paper presents a comparative analysis of the physical and biochemical aspects of predated sludge, providing insight into the hydrolytic mechanisms underlying WP. To this end, the sessile worm Tubifex tubifex was used as a model oligochaete and was batch cultivated in an 18-L airlift reactor. Predation on activated sludge showed an average reduction rate of 12 +/- 3.8%/d versus 2 +/- 1.3%/d for endogenous respirated sludge. Sludge predation resulted in an increased release of inorganic nitrogen, phosphate and soluble chemical oxygen demand (sCOD). The sCOD consisted mainly of polysaccharides; however, fluorescence excitation emission matrix spectroscopy analysis also revealed the presence of Tryptophan-protein-like substances. Results suggest that the released polysaccharides contain a protein-like element. Additionally, soluble iron increased slightly in concentration after WP. The extent of hydrolysis seemed to reach an average plateau of about 40% volatile solids (VS) reduction after 4 days, which is substantially higher than the 29% VS reduction for endogenous decay of activated sludge after 30 days. Furthermore, T. tubifex predominantly consumed the protein fraction of the extracellular polymeric substances. Results suggest that that the worms specifically target a fraction of the sludge that is predominantly biodegradable under aerobic conditions, albeit at significantly higher degradation rates when compared to the endogenous decay of waste activated sludge. PMID- 27680673 TI - Habitat Heterogeneity Variably Influences Habitat Selection by Wild Herbivores in a Semi-Arid Tropical Savanna Ecosystem. AB - An understanding of the habitat selection patterns by wild herbivores is critical for adaptive management, particularly towards ecosystem management and wildlife conservation in semi arid savanna ecosystems. We tested the following predictions: (i) surface water availability, habitat quality and human presence have a strong influence on the spatial distribution of wild herbivores in the dry season, (ii) habitat suitability for large herbivores would be higher compared to medium-sized herbivores in the dry season, and (iii) spatial extent of suitable habitats for wild herbivores will be different between years, i.e., 2006 and 2010, in Matetsi Safari Area, Zimbabwe. MaxEnt modeling was done to determine the habitat suitability of large herbivores and medium-sized herbivores. MaxEnt modeling of habitat suitability for large herbivores using the environmental variables was successful for the selected species in 2006 and 2010, except for elephant (Loxodonta africana) for the year 2010. Overall, large herbivores probability of occurrence was mostly influenced by distance from rivers. Distance from roads influenced much of the variability in the probability of occurrence of medium-sized herbivores. The overall predicted area for large and medium-sized herbivores was not different. Large herbivores may not necessarily utilize larger habitat patches over medium-sized herbivores due to the habitat homogenizing effect of water provisioning. Effect of surface water availability, proximity to riverine ecosystems and roads on habitat suitability of large and medium-sized herbivores in the dry season was highly variable thus could change from one year to another. We recommend adaptive management initiatives aimed at ensuring dynamic water supply in protected areas through temporal closure and or opening of water points to promote heterogeneity of wildlife habitats. PMID- 27680675 TI - Locomotion Disorders and Skin and Claw Lesions in Gestating Sows Housed in Dynamic versus Static Groups. AB - Lameness and lesions to the skin and claws of sows in group housing are commonly occurring indicators of reduced welfare. Typically, these problems are more common in group housing than in individual housing systems. Group management type (dynamic versus static) and stage of gestation influence the behavior of the animals, which in turn influences the occurrence of these problems. The present study compared prevalence, incidence and mean scores of lameness and skin and claw lesions in static versus dynamic group housed sows at different stages of gestation during three consecutive reproductive cycles. A total of 10 Belgian sow herds were monitored; 5 in which dynamic groups and 5 in which static groups were utilized. All sows were visually assessed for lameness and skin lesions three times per cycle and the claws of the hind limbs were assessed once per cycle. Lameness and claw lesions were assessed using visual analogue scales. Static groups, in comparison with dynamic groups, demonstrated lower lameness scores (P<0.05) and decreased skin lesion prevalence (24.9 vs. 47.3%, P<0.05) at the end of gestation. There was no difference between treatment group regarding claw lesion prevalence with 75.5% of sows demonstrating claw lesions regardless of group management. Prevalences of lameness (22.4 vs. 8.9%, P<0.05) and skin lesions (46.6 vs. 4.4%, P<0.05) were highest during the group-housed phase compared to the individually housed phases. Although the prevalence of lameness and skin lesions did not differ three days after grouping versus at the end of the group-housing phase, their incidence peaked during the first three days after moving from the insemination stalls to the group. In conclusion, the first three days after grouping was the most risky period for lameness incidence, but there was no significant difference between static or dynamic group management. PMID- 27680676 TI - Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner. AB - Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF 1alpha protein in human lung epithelial-like cells under non-hypoxic conditions. Genes upregulated by HIF-1, including vascular endothelial growth factor and regulated in development and DNA damage response 1, both of which are involved in smoking-induced emphysematous changes, were increased by CSE treatment under non hypoxic conditions in vitro and in vivo. Further investigation revealed that reactive oxygen species were generated in cells exposed to CSE and were required for CSE-mediated induction of HIF-1alpha protein, as was activation of phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. In conclusion, we demonstrated that CSE and CS induced HIF-1 activation in vitro and in vivo, respectively. The evidence warrants further investigation to indicate that HIF-1 plays an important role in CS-induced gene expression, which is deeply involved in pulmonary cellular stress and small airway remodelling. PMID- 27680677 TI - Mutations in actin used for structural studies partially disrupt beta thymosin/WH2 domains interaction. AB - Understanding the structural basis of actin cytoskeleton remodeling requires stabilization of actin monomers, oligomers, and filaments in complex with partner proteins, using various biochemical strategies. Here, we report a dramatic destabilization of the dynamic interaction with a model beta-thymosin/WH2 domain induced by mutations in actin. This result underlines that mutant actins should be used with prudence to characterize interactions with intrinsically disordered partners as destabilization of dynamic interactions, although identifiable by NMR, may be invisible to other structural techniques. It also highlights how both beta-thymosin/WH2 domains and actin tune local structure and dynamics in regulatory processes involving intrinsically disordered domains. PMID- 27680679 TI - The preparation of gamma-crystalline non-electrically poled photoluminescant ZnO PVDF nanocomposite film for wearable nanogenerators. AB - Polyvinylidene fluoride (PVDF) films are filled with various mass fractions (wt%) of zinc oxide nanoparticles (ZnO-NPs) to fabricate the high performance of a wearable polymer composite nanogenerator (PCNG). The ZnO-NPs can induced a fully gamma-crystalline phase in PVDF, where traditional electrical poling is not necessary for the generation of piezoelectric properties. The PCNG delivers up to 28 V of open circuit voltage and 450 nA of short circuit current by simple repeated human finger imparting (under a pressure amplitude of 8.43 kPa) that generates sufficient power to turn on at least 48 commercial blue light emitting diodes (LEDs) instantly. Furthermore, it also successfully charged the capacitors, signifying practical applicability as a piezoelectric based nanogenerator for self-powering devices. The applicability of PCNG by wearable means is clarified when it gives rise to a sensible response, say up to 400 mV of output voltage synchronized with the PCNG embedded human finger in a bending and releasing gesture. UV-visible absorption spectral analysis revealed the possibility of estimating a change in the optical band gap value (E g), refractive index (n) and optical activation energy (E a) in different concentrations of ZnO-NP incorporated PVDF nanocomposite films, and it possesses a useful methodology where ZnO-NPs can be used as an optical probe. Near blue light emission is observed from photoluminescence spectra, which are clearly shown from a Commission Internationale de L'Eclairage (CIE) diagram. The piezoelectric charge coefficient of the nanocomposite film is estimated to be 6.4 pC/N, where even electrical poling treatment is not employed. In addition, dielectric properties have been studied to understand the role of molecular kinetic and interfacial polarization occurring in nanocomposite films at different applied frequencies. PMID- 27680678 TI - In vitro beta-Carotene Bioaccessibility and Lipid Digestion in Emulsions: Influence of Pectin Type and Degree of Methyl-Esterification. AB - Citrus pectin (CP) and sugar beet pectin (SBP) were demethoxylated and fully characterized in terms of pectin properties in order to investigate the influence of the pectin degree of methyl-esterification (DM) and the pectin type on the in vitro beta-carotene bioaccessibility and lipid digestion in emulsions. For the CP based emulsions containing beta-carotene enriched oil, water and pectin, the beta carotene bioaccessibility, and lipid digestion were higher in the emulsions with pectin with a higher DM (57%; "CP57 emulsion") compared to the emulsions with pectin with a lower DM (30%; "CP30 emulsion") showing that the DM plays an important role. In contrast, in SBP-based emulsions, nor beta-carotene bioaccessibility nor lipid digestion were dependent on pectin DM. Probably here, other pectin properties are more important factors. It was observed that beta carotene bioaccessibility and lipid digestion were lower in the CP30 emulsion in comparison with the CP57, SBP32, and SBP58 emulsions. However, the beta-carotene bioaccessibility of CP57 emulsion was similar to that of the SBP emulsions, whereas the lipid digestion was not. It seems that pectin type and pectin DM (in case of CP) are determining which components can be incorporated into micelles. Because carotenoids and lipids have different structures and polarities, their incorporation may be different. This knowledge can be used to engineer targeted (digestive) functionalities in food products. If both high beta-carotene bioaccessibility and high lipid digestion are targeted, SBP emulsions are the best options. The CP57 emulsion can be chosen if high beta-carotene bioaccessibility but lower lipid digestion is desired. PMID- 27680680 TI - MicroRNA-21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway. AB - MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)-induced injury. Here, we investigated the function of miR-21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR-21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR-21+ H/R) group, (miR-21-negative control + H/R) group, (BEZ235+ H/R) group and (miR-21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs. Cell count kit-8 was used to evaluate cell function and apoptosis was analysed by Western blotting. Western blotting and transmission electron microscopy were used to investigate autophagy. We found that miR-21 expression was down-regulated, and autophagy was remarkably increased in H9c2 cells during H/R injury. Overexpression of miR-21 with a miR-21 precursor significantly inhibited autophagic activity and decreased apoptosis, accompanied by the activation of the AKT/mTOR pathway. In addition, treatment with BEZ235, a novel dual Akt/mTOR inhibitor, resulted in a significant increase in autophagy and apoptosis. However, we found that miR-21-mediated inhibition of apoptosis and autophagy was partly independent of Akt/mTOR activation, as demonstrated in cells treated with both miR-21 and BEZ235. We showed that miR-21 could inhibit H/R-induced autophagy and apoptosis, which may be at least partially mediated by the Akt/mTOR signalling pathway. PMID- 27680681 TI - alpha3beta1 Integrin Suppresses Prostate Cancer Metastasis via Regulation of the Hippo Pathway. AB - Existing anticancer strategies focused on disrupting integrin functions in tumor cells or tumor-involved endothelial cells have met limited success. An alternative strategy is to augment integrin-mediated pathways that suppress tumor progression, but how integrins can signal to restrain malignant behavior remains unclear. To address this issue, we generated an in vivo model of prostate cancer metastasis via depletion of alpha3beta1 integrin, a correlation observed in a significant proportion of prostate cancers. Our data describe a mechanism whereby alpha3beta1 signals through Abl family kinases to restrain Rho GTPase activity, support Hippo pathway suppressor functions, and restrain prostate cancer migration, invasion, and anchorage-independent growth. This alpha3beta1-Abl kinase-Hippo suppressor pathway identified alpha3 integrin-deficient prostate cancers as potential candidates for Hippo-targeted therapies currently under development, suggesting new strategies for targeting metastatic prostate cancer based on integrin expression. Our data also revealed paradoxical tumor suppressor functions for Abl kinases in prostate cancer that may help to explain the failure of Abl kinase inhibitor imatinib in prostate cancer clinical trials. Cancer Res; 76(22); 6577-87. (c)2016 AACR. PMID- 27680683 TI - Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis. AB - The innate immunoregulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells to stimulate antitumor T-cell immunity. Here, we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically, STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase, which generates STING-activating cyclic dinucleotides after binding cytosolic DNA species. Loss of STING function rendered melanoma cells unable to produce type I IFN and other immune cytokines after exposure to cytosolic DNA species. Consequently, such cells were highly susceptible to infection with DNA viruses including HSV1, a variant of which is being developed presently as a therapeutic oncolytic virus [talimogene laherparepvec (T-VEC)]. Our findings provide insight into the basis for susceptibility to viral oncolysis by agents such as HSV1. Cancer Res; 76(22); 6747-59. (c)2016 AACR. PMID- 27680682 TI - Preclinical Validation of a Single-Treatment Infusion Modality That Can Eradicate Extremity Melanomas. AB - Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a nongenotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here, we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137. The ability to bind DNA quickly combined with a favorable safety profile made it possible to substitute CBL0137 in the ILP protocol, using an intra-arterial infusion method, to safely achieve effective tumor suppression. Our findings of a preclinical proof of concept for CBL0137 and its administration via intra-arterial infusion as a superior treatment compared with melphalan ILP allows for locoregional treatment anywhere a catheter can be placed. Cancer Res; 76(22); 6620-30. (c)2016 AACR. PMID- 27680684 TI - Doxorubicin-Induced Systemic Inflammation Is Driven by Upregulation of Toll-Like Receptor TLR4 and Endotoxin Leakage. AB - Doxorubicin is one of the most effective chemotherapeutic agents used for cancer treatment, but it causes systemic inflammation and serious multiorgan side effects in many patients. In this study, we report that upregulation of the proinflammatory Toll-like receptor TLR4 in macrophages by doxorubicin is an important step in generating its toxic side effects. In patient serum, doxorubicin treatment resulted in leakage of endotoxin and inflammatory cytokines into circulation. In mice, doxorubicin damaged the intestinal epithelium, which also resulted in leakage of endotoxin from the gut flora into circulation. Concurrently, doxorubicin increased TLR4 expression in macrophages both in vitro and in vivo, which further enhanced the sensitivity of these cells to endotoxin. Either depletion of gut microorganisms or blockage of TLR4 signaling effectively decreased doxorubicin-induced toxicity. Taken together, our findings suggest that doxorubicin-triggered leakage of endotoxin into the circulation, in tandem with enhanced TLR4 signaling, is a candidate mechanism underlying doxorubicin-induced systemic inflammation. Our study provides new insights for devising relevant strategies to minimize the adverse effects of chemotherapeutic agents such as doxorubicin, which may extend its clinical uses to eradicate cancer cells. Cancer Res; 76(22); 6631-42. (c)2016 AACR. PMID- 27680685 TI - CCR2 Influences T Regulatory Cell Migration to Tumors and Serves as a Biomarker of Cyclophosphamide Sensitivity. AB - The CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4+ T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2+ Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen-specific cells in the dLN, where they displayed an activated immunosuppressive phenotype. Notably, in mouse models, low-dose cyclophosphamide treatment preferentially depleted CCR2+ Treg, enhancing priming of tumor-specific CD8+ T cells. In the MMTV-PyMT transgenic mouse model of breast cancer and in oral squamous cell carcinoma patients, tumor development was associated with decreased blood frequency and inversely increased tumor frequency of CCR2+ Tregs. Our results define a novel subset of CCR2+ Treg involved in tumoral immune escape, and they offer evidence that this Treg subset may be preferentially eradicated by low-dose cyclophosphamide treatment. Cancer Res; 76(22); 6483-94. (c)2016 AACR. PMID- 27680686 TI - Japanese-language Dementia Knowledge Assessment Scale: Psychometric performance, and health student and professional understanding. AB - AIM: Dementia prevalence is accelerating internationally commensurate with population aging. Super-aging countries, including Japan, will experience growing prevalence of this life-limiting condition in the coming decades as a result of falling fertility and mortality. The authors developed and verified a Japanese translation of the Dementia Knowledge Assessment Scale (DKAS-J) to address the paucity of reliable and valid Japanese-language measures, and to elucidate current understanding. METHODS: The present study was designed as exploratory research across five universities in Japan. The Dementia Knowledge Assessment Scale was translated into Japanese by a native speaker and bilingual physician with back-translation carried out to ensure consistency of meaning. Between January and April 2016, the DKAS-J was administered to 185 health students, academics and health professionals from the disciplines of nursing, medicine and allied health in the regions of Kyushu, Kansai and Tohoku. RESULTS: The DKAS-J showed face and content validity, acceptable internal consistency (alpha = 0.79) and adequate sensitivity (discrimination between health professionals and health students). A principal components analysis confirmed that an 18-item iteration of the DKAS-J performed optimally as a unidimensional scale. The results of DKAS-J administration showed low levels of dementia knowledge among participants, with particularly poor understanding related to the clinical course of the syndrome, symptomatology and the efficacy of pharmaceutical intervention for behavioral symptoms. CONCLUSION: The DKAS-J provides a useful tool for conceptualizing baseline knowledge, changes in understanding and knowledge deficits. Such a measure will prove valuable for the design and development of educational interventions as dementia increases in Japan and worldwide. Geriatr Gerontol Int 2017; 17: 1746-1751. PMID- 27680688 TI - Probing electrical tuning of hair cells with a Zap current method in the intact amphibian papilla of bullfrogs. AB - Most, if not all, modern vertebrate species have evolved exquisite inner ears to discriminate acoustic signals of different frequencies, through a process called frequency tuning. For non-mammalian species, at least part of frequency tuning has been attributed to intrinsic electrical properties of hair cells, i.e. electrical tuning. Since it was first discovered, the traditional method to assess electrical tuning has been to inject step current into hair cells and examine dampened membrane voltage oscillation. However, this method is not applicable for hair cells that do not oscillate. In this study, we developed a Zap current method that can be unbiasedly applied to all hair cells regardless of their oscillating behavior. Similar to a chirp sound in acoustic stimulation, a Zap current is a sinusoidal current with the frequency increased linearly with time. We first validated this new method with the traditional step current method on hair cells with dampened membrane voltage oscillation, and then applied it to all hair cells in the intact amphibian papilla of bullfrogs. We found that while hair cells with dampened membrane voltage oscillation are sharply tuned, non oscillating hair cells are broadly tuned. In addition, we found a third type of hair cells, which oscillate continuously and are extremely sharply tuned, with multiple peaks that are reminiscent of harmonics in the mammalian cochlea. In conclusion, the new Zap current method provides an unbiased way to assess electrical tuning, and it reveals an underappreciated heterogeneity of electrical tuning in the bullfrog amphibian papilla. PMID- 27680687 TI - Obesity and pregnancy outcomes: Do the relationships differ by maternal region of birth? A retrospective cohort study. AB - BACKGROUND: We aimed to determine whether the association between obesity and a range of adverse maternal and perinatal outcomes differed in South Asian and Australian and New Zealand born women. METHODS: A retrospective cohort study of singleton births in South Asian (SA) and Australian/New Zealand (AUS/NZ) born women at an Australian hospital between 2009 and 2013. The interaction between maternal region of birth and obesity on a range of maternal and perinatal outcomes was assessed using multivariate logistic regression. RESULTS: Obesity was more strongly associated with gestational hypertension/Preeclampsia/HELLP and Gestational Diabetes Mellitus in AUS/NZ born women (p = 0.001 and p < 0.001, respectively for interaction) and was only associated with shoulder dystocia in SA born women (p = 0.006 for interaction). There was some evidence that obesity was more strongly related with admission to NICU/Special care nursery (SCN) (p = 0.06 for interaction) and any perinatal morbidity (p = 0.05 for interaction) in SA born women. CONCLUSIONS: Interventions targeted at reducing maternal obesity will have different impacts in SA compared to AUS/NZ born women. PMID- 27680690 TI - Risk factors for hepatocellular carcinoma. PMID- 27680691 TI - Familial white lentiginosis. PMID- 27680689 TI - Establishment of in vitro soybean aphids, Aphis glycines (Hemiptera: Aphididae): a tool to facilitate studies of aphid symbionts, plant-insect interactions and insecticide efficacy. AB - BACKGROUND: Studies on plant-insect interactions of the soybean aphid, Aphis glycines (Matsumura), can be influenced by environmental fluctuations, status of the host plant and variability in microbial populations. Maintenance of aphids on in vitro-grown plants minimizes environmental fluctuations, provides uniform host materials and permits the selective elimination of aphid-associated microbes for more standardized controls in aphid research. RESULTS: Aphids were reared on sterile, in vitro-grown soybean seedlings germinated on plant tissue culture media amended with a mixture of antimicrobials. For initiation and maintenance of in vitro aphid colonies, single aphids were inoculated onto single in vitro seedlings. After three rounds of transfer of 'clean' aphids to fresh in vitro seedlings, contamination was no longer observed, and aphids performed equally well when compared with those reared on detached leaves. The addition of the insecticides thiamethoxam and chlorantraniliprole to the culture medium confirmed uptake and caused significant mortality to the in vitro aphids. The use of the antimicrobial mixture removed the associated bacteria Arsenophonus but retained Buchnera and Wolbachia within the in vitro aphids. CONCLUSION: The in vitro aphid system is a novel and highly useful tool to understand insecticidal efficacy and expand our knowledge of tritrophic interactions among plants, insects and symbionts. (c) 2016 Society of Chemical Industry. PMID- 27680692 TI - Therapy for Adult Social Anxiety Disorder: A Meta-Analysis of Functional Neuroimaging Studies. AB - OBJECTIVE: We conducted a meta-analysis of the literature reporting neuroimaging in patients undergoing psychotherapy and pharmacotherapy for social anxiety disorder (SAD). DATA SOURCES: Using PubMed, MEDLINE, and Embase, we searched for English-language studies published between January 2000 and February 2015 with terms related to SAD, therapy, and neuroimaging. STUDY SELECTION: Twelve studies were included with a total of 295 subjects with SAD before and after therapy from January 2000 to February 2015. DATA EXTRACTION: We extracted peak coordinates of clusters of significant group differences and performed a meta-analysis using effect-size signed differential mapping to analyze the peak coordinates of clusters and thresholds. RESULTS: Therapy significantly reduced activity in the left inferior parietal gyrus (Z = 1.441; P < .001), right postcentral gyrus (Z = 1.711; P < .001), and right precuneus (Z = 1.352; P < .01) and increased activity in the left inferior frontal gyrus/insula (Z = 1.939; P < .001) and bilateral middle cingulate gyrus (Z = 1.836; P < .001). Psychotherapy significantly increased activity in the bilateral precuneus (Z = 2.259; P < .001) and left inferior parietal gyrus (Z = 1.786; P < .001) and decreased activity in the left anterior cingulate gyrus (Z = 1.707; P < .001), left middle frontal gyrus (Z = 1.584; P < .001), and right cerebellum (Z = 1.424; P < .01). Pharmacotherapy increased activity in the right postcentral gyrus (Z = 1.215; P < .01), left middle occipital gyrus (Z = 1.269; P < .01), and right medial orbital frontal gyrus (Z = 1.250; P < .01) and reduced activity in the bilateral insula (Z = 2.172; P < .001; Z = 1.608; P < .01) and left medial cingula (Z = 1.479; P < .01). The improvement in social anxiety symptoms was positively associated with hyperactivity of the bilateral precuneus, left inferior partial gyrus, right medial cingulate, and right postcentral gyrus but negatively associated with hypoactivity of the bilateral insula and right medial cingulate (P < .01). We did not find any difference of amygdala among these 3 groups. CONCLUSIONS: Previous reports of brain imaging suggest that pharmacotherapy and psychotherapy impact different brain regions in adult patients with SAD. PMID- 27680693 TI - An integrative review on women living with obstetric fistula and after treatment experiences. AB - AIMS AND OBJECTIVES: To review literature on the experiences of women with obstetric fistula, their lived experiences after treatment; and to provide evidence for future research. BACKGROUND: Obstetric fistula is an injury most commonly resulting from a prolonged labour. Long eradicated in developed countries, obstetric fistula remains a public health issue in sub-Saharan Africa and Asia. This is a highly stigmatised health condition, and an understanding of the women's experience is required to inform holistic approaches for care and prevention. DESIGN: A search of literature was conducted on databases of EBSCO host (Academic Search Premier, MEDLINE, PsychINFO, CINAHL), Web of Science; and websites of international organizations such as Women's Dignity Project and EngenderHealth. Keywords, Inclusion and exclusion criteria were defined and 25 articles published between 2004 to January 2015 were identified. METHODS: An integrative review of 25 articles was carried out. RESULTS: Three broad themes were identified: Challenges of living with fistula; treatment and care experiences; and reintegration experiences of women after fistula repair. CONCLUSIONS: Living with a fistula presents multidimensional consequences affecting women, families and communities. Accessing treatment is difficult and there are no standardised treatment packages. Surgical repairs were variable in their success rate. Some authors claim women resume normal lives irrespective of their continence status, whilst others claim they face discrimination despite being continent thereby hindering reintegration. Quality of life is diminished for those remaining incontinent. Post repair psychosocial support services are beneficial for reintegration, but research on programme benefits is limited. Therefore further research is required to support its benefits; and for policy development to meet care provision for women with fistula. RELEVANCE TO CLINICAL PRACTICE: The review provides insights into avenues of improving care provision and delivery by health professionals and policy makers. It also exposes areas that need further research for quality care provision. PMID- 27680695 TI - Corrigendum: An early geodynamo driven by exsolution of mantle components from Earth's core. PMID- 27680696 TI - Erratum: Replication fork stability confers chemoresistance in BRCA-deficient cells. PMID- 27680697 TI - Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. AB - The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity. PMID- 27680698 TI - Autocrine BDNF-TrkB signalling within a single dendritic spine. AB - Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity, including structural long-term potentiation (sLTP), which is a correlate of an animal's learning. However, it is unknown whether BDNF release and TrkB activation occur during sLTP, and if so, when and where. Here, using a fluorescence resonance energy transfer-based sensor for TrkB and two-photon fluorescence lifetime imaging microscopy, we monitor TrkB activity in single dendritic spines of CA1 pyramidal neurons in cultured murine hippocampal slices. In response to sLTP induction, we find fast (onset < 1 min) and sustained (>20 min) activation of TrkB in the stimulated spine that depends on NMDAR (N-methyl-d-aspartate receptor) and CaMKII signalling and on postsynaptically synthesized BDNF. We confirm the presence of postsynaptic BDNF using electron microscopy to localize endogenous BDNF to dendrites and spines of hippocampal CA1 pyramidal neurons. Consistent with these findings, we also show rapid, glutamate-uncaging-evoked, time-locked BDNF release from single dendritic spines using BDNF fused to superecliptic pHluorin. We demonstrate that this postsynaptic BDNF-TrkB signalling pathway is necessary for both structural and functional LTP. Together, these findings reveal a spine-autonomous, autocrine signalling mechanism involving NMDAR-CaMKII-dependent BDNF release from stimulated dendritic spines and subsequent TrkB activation on these same spines that is crucial for structural and functional plasticity. PMID- 27680700 TI - Animal behaviour: Lethal violence deep in the human lineage. PMID- 27680701 TI - The phylogenetic roots of human lethal violence. AB - The psychological, sociological and evolutionary roots of conspecific violence in humans are still debated, despite attracting the attention of intellectuals for over two millennia. Here we propose a conceptual approach towards understanding these roots based on the assumption that aggression in mammals, including humans, has a significant phylogenetic component. By compiling sources of mortality from a comprehensive sample of mammals, we assessed the percentage of deaths due to conspecifics and, using phylogenetic comparative tools, predicted this value for humans. The proportion of human deaths phylogenetically predicted to be caused by interpersonal violence stood at 2%. This value was similar to the one phylogenetically inferred for the evolutionary ancestor of primates and apes, indicating that a certain level of lethal violence arises owing to our position within the phylogeny of mammals. It was also similar to the percentage seen in prehistoric bands and tribes, indicating that we were as lethally violent then as common mammalian evolutionary history would predict. However, the level of lethal violence has changed through human history and can be associated with changes in the socio-political organization of human populations. Our study provides a detailed phylogenetic and historical context against which to compare levels of lethal violence observed throughout our history. PMID- 27680699 TI - De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure. AB - BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals-50 unit cells per edge, on average-has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine- and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation. PMID- 27680703 TI - Corrigendum: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells. PMID- 27680704 TI - Projected land photosynthesis constrained by changes in the seasonal cycle of atmospheric CO2. AB - Uncertainties in the response of vegetation to rising atmospheric CO2 concentrations contribute to the large spread in projections of future climate change. Climate-carbon cycle models generally agree that elevated atmospheric CO2 concentrations will enhance terrestrial gross primary productivity (GPP). However, the magnitude of this CO2 fertilization effect varies from a 20 per cent to a 60 per cent increase in GPP for a doubling of atmospheric CO2 concentrations in model studies. Here we demonstrate emergent constraints on large-scale CO2 fertilization using observed changes in the amplitude of the atmospheric CO2 seasonal cycle that are thought to be the result of increasing terrestrial GPP. Our comparison of atmospheric CO2 measurements from Point Barrow in Alaska and Cape Kumukahi in Hawaii with historical simulations of the latest climate-carbon cycle models demonstrates that the increase in the amplitude of the CO2 seasonal cycle at both measurement sites is consistent with increasing annual mean GPP, driven in part by climate warming, but with differences in CO2 fertilization controlling the spread among the model trends. As a result, the relationship between the amplitude of the CO2 seasonal cycle and the magnitude of CO2 fertilization of GPP is almost linear across the entire ensemble of models. When combined with the observed trends in the seasonal CO2 amplitude, these relationships lead to consistent emergent constraints on the CO2 fertilization of GPP. Overall, we estimate a GPP increase of 37 +/- 9 per cent for high-latitude ecosystems and 32 +/- 9 per cent for extratropical ecosystems under a doubling of atmospheric CO2 concentrations on the basis of the Point Barrow and Cape Kumukahi records, respectively. PMID- 27680702 TI - XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer. AB - The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity. However, advances have been hindered by the pervasive inter- and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies. Here we demonstrate the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. Nuclear transport machinery was the sole process-level discriminator of statistical significance. Chemical perturbation of the nuclear export receptor XPO1 (also known as CRM1), with a clinically available drug, revealed a robust synthetic-lethal interaction with native or engineered oncogenic KRAS both in vitro and in vivo. The primary mechanism underpinning XPO1 inhibitor sensitivity was intolerance to the accumulation of nuclear IkappaBalpha (also known as NFKBIA), with consequent inhibition of NFkappaB transcription factor activity. Intrinsic resistance associated with concurrent FSTL5 mutations was detected and determined to be a consequence of YAP1 activation via a previously unappreciated FSTL5-Hippo pathway regulatory axis. This occurs in approximately 17% of KRAS-mutant lung cancers, and can be overcome with the co-administration of a YAP1-TEAD inhibitor. These findings indicate that clinically available XPO1 inhibitors are a promising therapeutic strategy for a considerable cohort of patients with lung cancer when coupled to genomics-guided patient selection and observation. PMID- 27680694 TI - Genome-wide associations for birth weight and correlations with adult disease. AB - Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 * 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 * 10-13), T2D (Rg = -0.27, P = 1.1 * 10-6) and coronary artery disease (Rg = 0.30, P = 6.5 * 10-9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 * 10-4). We demonstrate that life course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated. PMID- 27680705 TI - The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila. AB - Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients. In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster. We found that knockdown of the coat protein complex I (COPI)-Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells. The dying stem cells were engulfed by neighbouring differentiated cells through a draper myoblast city-Rac1-basket (also known as JNK)-dependent autophagy pathway. Furthermore, Arf1 inhibitors reduced CSCs in human cancer cell lines. Thus, normal or cancer stem cells may rely primarily on lipid reserves for energy, in such a way that blocking lipolysis starves them to death. This finding may lead to new therapies that could help to eliminate CSCs in human cancers. PMID- 27680708 TI - Corrigendum: An essential receptor for adeno-associated virus infection. PMID- 27680707 TI - Atom-at-a-time laser resonance ionization spectroscopy of nobelium. AB - Optical spectroscopy of a primordial isotope has traditionally formed the basis for understanding the atomic structure of an element. Such studies have been conducted for most elements and theoretical modelling can be performed to high precision, taking into account relativistic effects that scale approximately as the square of the atomic number. However, for the transfermium elements (those with atomic numbers greater than 100), the atomic structure is experimentally unknown. These radioactive elements are produced in nuclear fusion reactions at rates of only a few atoms per second at most and must be studied immediately following their production, which has so far precluded their optical spectroscopy. Here we report laser resonance ionization spectroscopy of nobelium (No; atomic number 102) in single-atom-at-a-time quantities, in which we identify the ground-state transition 1S01P1. By combining this result with data from an observed Rydberg series, we obtain an upper limit for the ionization potential of nobelium. These accurate results from direct laser excitations of outer-shell electrons cannot be achieved using state-of-the-art relativistic many-body calculations that include quantum electrodynamic effects, owing to large uncertainties in the modelled transition energies of the complex systems under consideration. Our work opens the door to high-precision measurements of various atomic and nuclear properties of elements heavier than nobelium, and motivates future theoretical work. PMID- 27680709 TI - Isolation and Characterization of Mauritanicain, a Serine Protease from the Latex of Euphorbia mauritanica L. AB - A protease called Mauritanicain was isolated from the latex of Euphorbia mauritanica L. (Euphorbiaceae) by combining ion exchange chromatography, ultrafiltration, and gel filtration chromatography. It has a high proteolytic activity against casein. The activity was only inhibited by specific serine protease inhibitors, classifying it to the serine protease family. An optimal degradation of the substrate casein takes place at a temperature of 55-65 degrees C and a pH of 5.5-6.5, and is unstable at pH < 5 and pH > 9. The protease is stable at temperatures from 20-70 degrees C, whereby the activity decreases drastically to less than 20 % at 75 degrees C. SDS-PAGE and matrix-assisted laser desorption time-of-flight analysis yielded a molecular weight of 73 kDa; possibly, it is natively present as a non-covalently linked dimer of a higher molecular mass > 132 kDa. Without heat denaturation, a breakdown in fractions of 73 kDa and 52 kDa was observed in SDS-PAGE. Only in some properties it shows a similarity to other characterized proteases in the plant family Euphorbiaceae, such that Mauritanicain can be presented as a new isolated protease. PMID- 27680711 TI - Dissociating parafoveal preview benefit and parafovea-on-fovea effects during reading: A combined eye tracking and EEG study. AB - During reading, the parafoveal processing of an upcoming word n+1 can influence word recognition in two ways: It can affect fixation behavior during the preceding fixation on word n (parafovea-on-fovea effect, POF), and it can facilitate subsequent foveal processing once word n+1 is fixated (preview benefit). While preview benefits are established, evidence for POF effects is mixed. Recently, it has been suggested that POF effects exist, but have a delayed impact on saccade planning and thus coincide with preview benefits measured on word n+1. We combined eye movement and EEG recordings to investigate and separate neural correlates of POF and preview benefit effects. Participants read lists of nouns either in a boundary paradigm or the RSVP-with-flankers paradigm, while we recorded fixation- or event-related potentials (FRPs/ERPs), respectively. The validity and lexical frequency of the word shown as preview for the upcoming word n+1 were orthogonally manipulated. Analyses focused on the first fixation on word n+1. Preview validity (correct vs. incorrect preview) strongly modulated fixation times and electrophysiological N1 amplitudes, replicating previous findings. Importantly, gaze durations and FRPs measured on word n+1 were also affected by the frequency of the word shown as preview, with low-frequency previews eliciting a sustained, N400-like centroparietal negativity. Results support the idea that POF effects exist but affect word recognition with a delay. Lastly, once word n+1 was fixated, its frequency also modulated N1 amplitudes in ERPs and FRPs. Taken together, we separated immediate and delayed effects of parafoveal processing on brain correlates of word recognition. PMID- 27680710 TI - Prolonged survival with a longer duration of maintenance lenalidomide after autologous hematopoietic stem cell transplantation for multiple myeloma. AB - BACKGROUND: Although lenalidomide maintenance therapy has demonstrated improved outcomes after autologous hematopoietic stem cell transplantation (auto-HCT) for patients with multiple myeloma (MM), the impact of the duration of this therapy is not clearly known. METHODS: This study retrospectively analyzed all MM patients who were placed on maintenance lenalidomide after auto-HCT between January 2007 and December 2013. Progression-free survival (PFS) and overall survival (OS) were analyzed in multivariate Cox proportional hazards regression models that included the duration of maintenance as a time-dependent covariate. RESULTS: Of the 464 patients identified, 46% initiated therapy early (<4 months after auto-HCT). The median PFS and OS were 38 and 78 months, respectively. Improvements in PFS (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 0.38; P < .001) and OS (HR, 0.09; 95% CI, 0.03-0.26; P < .001) were seen for those on maintenance for >2 years versus those on maintenance for <=2 years. For those on maintenance for >3 versus those on maintenance for <=3 years, this trend continued with improvements seen in PFS (HR, 0.02; 95% CI, 0.00-0.44; P = .012) and OS (HR, 0.05; 95% CI, 0.00-0.83; P = .037). The incidence of second primary malignancies (SPMs) in the entire cohort was 3%. No differences were seen in survival between early and late initiators of maintenance lenalidomide. CONCLUSIONS: A longer duration of maintenance therapy was associated with longer survival. The incidence of SPMs was low, and they were not associated with the duration of maintenance. The timing of the initiation of maintenance had no effect on survival. Cancer 2016;122:3831-3837. (c) 2016 American Cancer Society. PMID- 27680706 TI - Frizzled proteins are colonic epithelial receptors for C. difficile toxin B. AB - Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9 mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium. PMID- 27680712 TI - Etoposide Induces Apoptosis in Activated Human Hepatic Stellate Cells via ER Stress. AB - The activation of hepatic stellate cells (HSCs) plays a vital role in the progression of liver fibrosis, and the induction of HSCs apoptosis may attenuate or reverse fibrogenesis. The therapeutic effects of etoposide(VP-16), a widely used anticancer agent, on HSCs apoptosis and liver fibrosis resolution are still unclear. Here, we report that VP-16 reduced the proliferation of LX-2 cells and led to significantly high levels of apoptosis, as indicated by Annexin V staining and the proteolytic cleavage of the executioner caspase-3 and PARP. Additionally, the unfolded protein response regulators CHOP, BIP, caspase-12, p-eIF2alpha and IRE1alpha, which are considered endoplasmic reticulum (ER) stress markers, were upregulated by VP-16. The strong inhibitory effect of VP-16 on LX-2 cells was mainly dependent on ER stress, which activated JNK signaling pathway. Remarkably, VP-16 treatment decreased the expression of alpha-SMA and type I collagen and simultaneously increased the ratio of matrix metalloproteinases (MMPs) to tissue inhibitor of matrix metalloproteinases (TIMPs). In contrast, VP-16 induced significantly more apoptosis in HSCs than in normal hepatocytes. Taken together, our findings demonstrate that VP-16 exerts a proapoptotic effect on LX-2 cells and has an antifibrogenic effect on collagen deposition, suggesting a new strategy for the treatment of liver fibrosis. PMID- 27680713 TI - Lesion distribution among 281 patients with sporadic neuralgic amyotrophy. AB - INTRODUCTION: The muscles commonly affected by neuralgic amyotrophy (NA) are well known, but the location of the responsible lesions is less clear (plexus versus extraplexus). METHODS: We report the lesion locations in 281 NA patients as determined by extensive electrodiagnostic (EDX) testing. RESULTS: Our 281 patients had 322 bouts of NA, 57 of which were bilateral, for a total of 379 assessable events. A single nerve was involved in 174 (46%), and 205 (54%) were multifocal. EDX testing identified 703 individual lesions: 699 neuropathies and 4 supraclavicular radiculoplexus lesions. CONCLUSIONS: The frequency of nerve involvement reflects the motor predilection of NA. Involvement of pure motor nerves exceeded that of predominantly motor nerves, both of which far exceeded involvement of more evenly mixed sensorimotor nerves. Cutaneous sensory nerves were least commonly involved. Because of the common C5-C6 innervation, NA often mimics an upper plexus lesion. Extraplexus nerve involvement far exceeded plexus involvement. Distal motor branch involvement explains the severe single-muscle wasting and weakness often observed. Muscle Nerve 55: 858-861, 2017. PMID- 27680714 TI - Recall and Cancer Detection Rates for Screening Mammography: Finding the Sweet Spot. AB - OBJECTIVE: The purpose of this study is to identify the optimal screening mammography recall rate range on the basis of cancer detection rates among breast imaging specialists at an academic institution. MATERIALS AND METHODS: Medical outcome audit data collected in accordance with the Mammography Quality Standards Act from September 1, 2007, through August 31, 2012, were reviewed. Cancer detection rates were calculated from 984 screen-detected cancers identified in 188,959 total digital screening mammograms. The percentages of minimally invasive and early-stage cancers were also calculated. The 75 annual recall rates were analyzed two ways. First, they were separated into recall groups to assess cancer detection rate variation by the recall categories using rate ratios: less than 10%, 10% to less than 12%, 12% to less than 14%, and 14% or higher. Next, a linear regression with bootstrap bias correction was performed to assess changes in cancer detection rate with each unit increase in the recall rate up to 20%, with the recall category of less than 7% taken as reference. Annual cancer detection rates for a physician were grouped according to annual percentage recall rate. RESULTS: Statistically significantly higher cancer detection rates were seen for recall rates 12% or higher, with rate ratios of 1.75 (95% CI, 1.40 2.19) and 2.06 (95% CI, 1.72-2.46) for the recall groups 12% to less than 14% and 14% and higher, respectively, compared with the less than 10% group. When taking the category 12% to less than 14% as the reference, there were no statistically significant differences between recall groups 12% to less than 14% and 14% or higher in cancer detection rate. A statistically significant increase in the cancer detection rate with each unit increase in the recall rate was seen only for recall rates 12% or higher. CONCLUSION: These observations suggest that the sweet spot for optimal cancer detection is in the recall rate range 12% to less than 14% with the incremental benefit above this to be relatively small. A recall rate less than 10% may be too low. PMID- 27680715 TI - Ba3(Cr0.97(1)Te0.03(1))2TeO9: in Search of Jahn-Teller Distorted Cr(II) Oxide. AB - A novel 6H-type hexagonal perovskite Ba3(Cr0.97(1)Te0.03(1))2TeO9 was prepared at high pressure (6 GPa) and temperature (1773 K). Both transmission electron microscopy and synchrotron powder X-ray diffraction data demonstrate that Ba3(Cr0.97(1)Te0.03(1))2TeO9 crystallizes in P63/mmc with face-shared (Cr0.97(1)Te0.03(1))O6 octahedral pairs interconnected with TeO6 octahedra via corner-sharing. Structure analysis shows a mixed Cr2+/Cr3+ valence state with ~10% Cr2+. The existence of Cr2+ in Ba3(Cr2+0.10(1)Cr3+0.87(1)Te6+0.03)2TeO9 is further evidenced by X-ray absorption near-edge spectroscopy. Magnetic properties measurements show a paramagnetic response down to 4 K and a small glassy-state curvature at low temperature. In this work, the octahedral Cr2+O6 component is stabilized in an oxide material for the first time; the expected Jahn-Teller distortion of high-spin (d4) Cr2+ is not found, which is attributed to the small proportion of Cr2+ (~10%) and the face-sharing arrangement of CrO6 octahedral pairs, which structurally disfavor axial distortion. PMID- 27680716 TI - Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of beta-casein: results from a randomized, cross over clinical trial. AB - : This study reports the plasma glutathione concentrations in a double-blind, randomized, controlled, 2 * 2 cross-over study in which healthy participants consumed conventional milk (2 * 250 mL per day) containing both A1 and A2 types of beta-casein, or milk containing only A2 type beta-casein. Beta-casomorphin-7 (BCM-7), a peptide uniquely derived from the A1 type of beta-casein, was previously reported to downregulate glutathione expression in human gut epithelial and neuronal cell lines by limiting cysteine uptake. The current human study demonstrates that consumption of milk containing only A2 beta-casein was associated with a greater increase in plasma glutathione concentrations compared with the consumption of milk containing both beta-casein types, and did not increase plasma BCM-7 concentrations compared with the washout diet in the study participants. Thus, milk containing only A2 beta-casein and not A1 beta-casein has the potential to promote the production of the antioxidant glutathione in humans. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02406469. PMID- 27680717 TI - Differential expression pattern of Vago in bumblebee (Bombus terrestris), induced by virulent and avirulent virus infections. AB - Viruses are one of the main drivers of the decline of domesticated and wild bees but the mechanisms of antiviral immunity in pollinators are poorly understood. Recent work has suggested that next to the small interfering RNA (siRNA) pathway other immune-related pathways play a role in the defense of the bee hosts against viral infection. In addition, Vago plays a role in the cross-talk between the innate immune pathways in Culex mosquito cells. Here we describe the Vago orthologue in bumblebees of Bombus terrestris, and investigated its role upon the infection of two different bee viruses, the virulent Israeli acute paralysis virus (IAPV) and the avirulent slow bee paralysis virus (SBPV). Our results showed that BtVago was downregulated upon the infection of IAPV that killed all bumblebees, but not with SBPV where the workers survived the virus infection. Thus, for the first time, Vago/Vago-like expression appears to be associated with the virulence of virus and may act as a modulator of antiviral immunity. PMID- 27680719 TI - The aphasia syndromes: Localization and classification. AB - The premise of this article is that the members of the stroke team speak an abbreviated but common language when discussing the person with aphasia. The team's initial goal is to assess a person with stroke who has sustained left hemisphere injury and to be able to communicate effectively with each other and the patient in order to accomplish the rehabilitation goals. The article discusses differential diagnosis in aphasia and the advantages and disadvantages of aphasia classification. Given that aphasia classification is a necessary clinical charge, the various definitions of aphasia are presented, since what one does with the person with aphasia depends on what one thinks aphasia is. The syndrome approach is described as the method of choice for classifying persons with aphasia, and the various aphasia syndromes are then described both in terms of behavior and site of lesion. Finally, clinical implications are discussed in the context of applying the syndrome approach to aphasia classification in stroke rehabilitation. PMID- 27680720 TI - Traditional and contemporary views of aphasia: implications for clinical management. AB - The following is an attempt to consider how various ways of thinking about the aphasic condition influence how the problem is approached for rehabilitation. The fundamental theory of three popular, traditional approaches to assessment of aphasia are considered with particular regard to their consequential influence upon clinical management. The possibilities and limitations of clinical integration of the relatively new approach of cognitive neuropsychology are discussed. PMID- 27680721 TI - An assessment tool for evaluating cognitive-communicative problems in patients with right hemisphere damage: Preliminary findings. AB - This article briefly describes the primary characteristics ofthe communication problems associated with right hemisphere damage. It presents a test battery, the RIC Evaluation of Communication Problems in Right Hemisphere Dysfunction-2 (RICE 2; Halper, Burns, Cherney, & Mogil, 1991), that has been developed for this population. Preliminary results of a study to validate the RICE-2 indicate that the tool is sensitive to measuring the differences between nonneurologically impaired individuals and right hemisphere stroke patients. Test scores of individual subjects who are representative of different cognitive-communicative severity levels are presented to illustrate variability in patterns of performance. PMID- 27680718 TI - Staphylococcus capitis isolated from prosthetic joint infections. AB - Further knowledge about the clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different coagulase-negative staphylococci (CoNS) may facilitate interpretation of microbiological findings and improve treatment algorithms. Staphylococcus capitis is a CoNS with documented potential for both human disease and nosocomial spread. As data on orthopaedic infections are scarce, our aim was to describe the clinical and microbiological characteristics of PJIs caused by S. capitis. This retrospective cohort study included three centres and 21 patients with significant growth of S. capitis during revision surgery for PJI between 2005 and 2014. Clinical data were extracted and further microbiological characterisation of the S. capitis isolates was performed. Multidrug-resistant (>=3 antibiotic groups) S. capitis was detected in 28.6 % of isolates, methicillin resistance in 38.1 % and fluoroquinolone resistance in 14.3 %; no isolates were rifampin-resistant. Heterogeneous glycopeptide-intermediate resistance was detected in 38.1 %. Biofilm-forming ability was common. All episodes were either early post interventional or chronic, and there were no haematogenous infections. Ten patients experienced monomicrobial infections. Among patients available for evaluation, 86 % of chronic infections and 70 % of early post-interventional infections achieved clinical cure; 90 % of monomicrobial infections remained infection-free. Genetic fingerprinting with repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab(r)) displayed clustering of isolates, suggesting that nosocomial spread might be present. Staphylococcus capitis has the potential to cause PJIs, with infection most likely being contracted during surgery or in the early postoperative period. As S. capitis might be an emerging nosocomial pathogen, surveillance of the prevalence of PJIs caused by S. capitis could be recommended. PMID- 27680722 TI - Pragmatic communication disorders following stroke. AB - This article provides the rehabilitation professional with a summary of current knowledge regarding the nature, implications, and management of pragmatic communication disorders following stroke. Alternative views and definitions of pragmatics are discussed. Pragmatic communication strengths and weaknesses following right and left cerebral hemisphere damage are described within the framework of verbal expression, verbal comprehension, paralinguistic skills, and nonverbal abilities. Assessment principles and practices are presented, and specific assessment tools and methodologies are described. The article includes a review of current treatment strategies for pragmatic communication disorders following stroke and provides a rationale for an emphasis on pragmatics in the rehabilitation of persons with communication disorders following stroke. PMID- 27680723 TI - Motor speech problems associated with stroke: The dysarthrias. AB - Dysarthria is one of a number of communication problems that may occur following a stroke. The presence of dysarthria can affect both rehabilitation efforts as well as social and vocational adjustment. This article reviews methods of classifying the dysarthrias and presents the types of dysarthria most often encountered poststroke. The characteristics of these dysarthria types are then related to the underlying neuropathology. Finally, a model of intervention that addresses the impairment, disability, and handicap of the dysarthria is presented. Specific examples of the role of the rehabilitation team in the management of dysarthria are provided. PMID- 27680724 TI - The effects of brain stem stroke on communication and swallowing. AB - A brain stem stroke frequently results in impairment of speech and/or swallowing. Symptoms may range from mild to severe, depending on the location and extent of the stroke. This article describes the brain stem's role in communication and swallowing, as well as evaluation and treatment of disorders caused by brain stem stroke. A number of brain stem syndromes that commonly impair speech and swallowing, including Wallenberg's syndrome and locked-in syndrome, are also discussed. PMID- 27680725 TI - Multiinfarct dementia and communication. AB - Traditionally, speech-language pathologists have treated patients who have suffered from strokes that resulted in aphasia, but have not always worked with patients labelled as having multiinfarct dementia (MID). Patients with MID also have difficulties with communication in which the speech-language pathologist's input would be beneficial. This article examines the clinical characteristics and neurology of MiD along with the assessment and clinical issues that need to be examined if speech-language pathologists are to evaluate and treat these patients more effectively. PMID- 27680726 TI - A second start. PMID- 27680727 TI - Assessing decisionmaking capacity in a patient with nondominant hemispheric stroke. PMID- 27680728 TI - Diagnosis and management of pneumonia and ventilatory disorders in patients with stroke. PMID- 27680731 TI - Letters to the Editors. PMID- 27680730 TI - From the editor. PMID- 27680729 TI - New technologies and intervention approaches. PMID- 27680732 TI - Foreword. PMID- 27680734 TI - Recurrent cerebral venous thrombosis revealing celiac disease: an exceptional case report. PMID- 27680733 TI - Predictors of intensive care unit utilization in patients with posterior reversible encephalopathy syndrome. AB - Posterior reversible encephalopathy syndrome (PRES) is an acute neurological syndrome that requires prompt, aggressive management to improve outcomes. Our aim was to identify factors that would necessitate care in the intensive care unit (ICU) in patients with PRES and the outcomes on discharge following ICU stay. We retrospectively reviewed the medical records and radiological data of adult PRES patients admitted to our tertiary care medical center. We dichotomized them into two groups based on their need for ICU care and compared their clinical, laboratory, imaging characteristics and discharge outcomes. Outcomes were defined using the modified Rankin Score (mRS) and Glasgow Outcome Score (GOS) on discharge. Out of 100 patients, 67 % required admission to the ICU. On univariate analysis, factors associated with ICU admission were atrial fibrillation (19.4 vs 0 %; p <= 0.05), encephalopathy from PRES (89.6 vs 66.7 %; p < 0.05), low Glasgow Coma Score (GCS) (11 +/- 4 vs 14 +/- 2; p = 0.01) and cortical involvement on imaging (89.6 vs 72.7 %, p = 0.03). On multivariate logistic regression analysis, encephalopathy (odds ratio 10.22; 95 % CI (1.14-91.55; p = 0.04) was the sole predictor of ICU utilization. This correlated with a GCS <12 (odds ratio 5.53; 95 % CI (1.05-29.22; p = 0.04). Despite worse functional outcomes following ICU care based on mRS (2.3 +/- 2.1 vs 1.3 +/- 1.4, p = 0.02) and GOS (3.9 +/- 1.3 vs 4.6 +/- 0.7, p <= 0.05), only a borderline increase in mortality was observed (10.4 vs 0 %, p = 0.05). The presence of PRES-related encephalopathy might aid in prompt identification of patients who require ICU care. PMID- 27680735 TI - Sulodexide for the extended treatment of venous thromboembolism. PMID- 27680736 TI - The grass isn't always greener: The effects of cannabis on embryological development. AB - With the increasing publicity of marijuana due to recent legislation, it is pertinent that the effects of fetal exposure to the drug are assessed. While in utero cannabis exposure has been associated with early pregnancy failure, birth defects and developmental delay, the mechanisms of such outcomes are largely unexplained. Furthermore, the use of cannabinoids in cancer treatment via growth inhibition and apoptosis may indicate how cannabis exposure likely harms a growing fetus. Cannabinoid signaling is required for proper pre-implantation development, embryo transport to the uterus, and uterine receptivity during implantation. In post-implantation development, cannabinoid signaling functions in a multitude of pathways, including, but not limited to, folic acid, VEGF, PCNA, MAPK/ERK, and BDNF. Disrupting the normal activity of these pathways can significantly alter many vital in utero processes, including angiogenesis, cellular replication, tissue differentiation, and neural cognitive development. This paper aims to demonstrate the effects of cannabis exposure on a developing embryo in order to provide a molecular explanation for the adverse outcomes associated with cannabis use during pregnancy. PMID- 27680738 TI - [Management of rheumatic diseases]. PMID- 27680737 TI - [Management of axial spondyloarthritis]. AB - The term spondyloarthritis (SpA) is now increasingly used to classify and diagnose patients who are characterized by inflammation in the axial skeleton and peripheral manifestations (arthritis and enthesitis). The management of SpA should be tailored according to the current manifestations of the disease, the disease activity and functional impairment. The current article focuses on diagnosis and therapy in patients with axial SpA. Diagnostic procedures are discussed in light of diagnostic utility and feasibility in daily routine care. Cornerstones of treatment in patients with axial SpA are a combination of regular exercise and pharmacological treatment options aiming at anti-inflammatory strategies. PMID- 27680739 TI - [Cardiovascular outcome in patients with COPD : Study to Understand Mortality and Morbidity (SUMMIT)]. PMID- 27680741 TI - Production of Cost-Effective Mesoporous Materials from Prawn Shell Hydrocarbonization. AB - In this work, prawn shell was studied as raw material for the production of mesoporous adsorbents via hydrocarbonization, studying the effect of temperature and time on the process reactivity and final characteristics of the hydrochars. By suitable characterization technique analyses (N2 adsorption at 77 K, SEM observation, ultimate analysis, surface composition), the materials were examined. It was found that in both cases mesoporous materials with low values of S BET due to the presence of CaCO3 on the material structure. In order to provide a potential application for these materials, the adsorption behaviour of hydrochars (HCs) as well as that of pristine prawn shells and ashes from prawn shell combustion was studied for the first time with the model compound p nitrophenol (PNP). The results indicated that HC treatment was beneficial and enhanced adsorption performance, especially at high values of equilibrium concentration, attaining adsorption capacities up to 1.6 mg g(-1). PMID- 27680740 TI - Detection of pH and Enzyme-Free H2O2 Sensing Mechanism by Using GdO x Membrane in Electrolyte-Insulator-Semiconductor Structure. AB - A 15-nm-thick GdO x membrane in an electrolyte-insulator-semiconductor (EIS) structure shows a higher pH sensitivity of 54.2 mV/pH and enzyme-free hydrogen peroxide (H2O2) detection than those of the bare SiO2 and 3-nm-thick GdO x membranes for the first time. Polycrystalline grain and higher Gd content of the thicker GdO x films are confirmed by transmission electron microscopy (TEM) and X ray photo-electron spectroscopy (XPS), respectively. In a thicker GdO x membrane, polycrystalline grain has lower energy gap and Gd(2+) oxidation states lead to change Gd(3+) states in the presence of H2O2, which are confirmed by electron energy loss spectroscopy (EELS). The oxidation/reduction (redox) properties of thicker GdO x membrane with higher Gd content are responsible for detecting H2O2 whereas both bare SiO2 and thinner GdO x membranes do not show sensing. A low detection limit of 1 MUM is obtained due to strong catalytic activity of Gd. The reference voltage shift increases with increase of the H2O2 concentration from 1 to 200 MUM owing to more generation of Gd(3+) ions, and the H2O2 sensing mechanism has been explained as well. PMID- 27680742 TI - Protective effect of 3-O-methyl quercetin and kaempferol from Semecarpus anacardium against H2O2 induced cytotoxicity in lung and liver cells. AB - BACKGROUND: Hydrogen peroxide is continuously generated in living cells through metabolic pathways and serves as a source of reactive oxygen species. Beyond the threshold level, it damages cells and causes several human disorders, including cancer. METHODS: Effect of isolated 3-O-methyl quercetin and kaempferol on H2O2 induced cytotoxicity, ROS formation, plasma membrane damage, loss of mitochondrial membrane potential, DNA damage was evaluated in normal liver and lung cells. The RT-PCR analysis used to determine Nrf 2 gene expression. Calorimetric ELISA was used to determine Nrf2 and p-38 levels. Expression of SOD and catalase was analyzed by Western blot analysis. RESULTS: The present study isolated 3-O-methyl quercetin and kaempferol from the stem bark. They protected normal lung and liver cells from H2O2 induced cytotoxicity, ROS formation, membrane damage and DNA damage. Pre-treatment with 3-O-methyl quercetin and kaempferol caused translocation of Nrf2 from cytosol to nucleus. It also increased expression of p-p38, Nrf2, SOD and catalase in H2O2 treated lung and liver cells. CONCLUSION: The flavonoids isolated from S. anacardium significantly reduced H2O2 induced stress and increased expression of Nrf2, catalase and superoxide dismutase-2 indicating cytoprotective nature of 3-O-methylquercetin and kaempferol. PMID- 27680744 TI - Successful replacement of the systemic tricuspid valve with a mechanical valve in a 3-month-old boy with congenitally corrected transposition of the great arteries having a dysplastic tricuspid valve. AB - There are a few reports of successful replacement of the left-sided systemic tricuspid valve with a mechanical valve in small infants with congenitally corrected transposition of the great arteries having Ebstein's anomaly. Tricuspid valve replacement is the preferred option when pulmonary artery banding, performed as a prelude to performing the double-switch operation, is not feasible because of severe heart failure caused by tricuspid regurgitation. PMID- 27680743 TI - Awake whole-brain functional connectivity alterations in the adolescent spontaneously hypertensive rat feature visual streams and striatal networks. AB - Brain mechanisms underpinning attention deficit/hyperactivity disorder (ADHD) are incompletely understood. The adolescent spontaneously hypertensive rat (SHR) is a widely studied preclinical model that expresses several of the key behavioral features associated with ADHD. Yet, little is known about large-scale functional connectivity patterns in the SHR, and their potential similarity to those of humans with ADHD. Using an approach comparable to human studies, magnetic resonance imaging in the awake animal was performed to identify whole-brain intrinsic neural connectivity patterns. An independent components analysis of resting-state functional connectivity demonstrated many common components between the SHR and both Wistar Kyoto and Sprague-Dawley control strains, but there was a divergence in other networks. In the SHR, three functional networks involving the striatum had only weak correlations with networks in the two control strains. Conversely, networks involving the visual cortex that was present in both control strains had only weak correlations with networks in the SHR. The implication is that the patterns of brain activity differ between the SHR and the other strains, suggesting that brain connectivity patterns in this animal model of ADHD may provide insights into the neural basis of ADHD. Brain connectivity patterns might also serve to identify brain circuits that could be targeted for the manipulation and evaluation of potential therapeutic options. PMID- 27680745 TI - Nanomolar Hg2+ Detection Using beta-Lactoglobulin-Stabilized Fluorescent Gold Nanoclusters in Beverage and Biological Media. AB - Owing to diverse functionalities and metal binding abilities, proteins have been proven to be promising ligands in the synthesis of gold nanoclusters (Au NCs). In this work, we explored beta-lactoglobulin (beta-Lg), a protein byproduct generated during cheese processing, as a biotemplate for fabrication of Au NCs by a facile and green method for the first time. The as-prepared Au NCs are water soluble and highly fluorescent and exhibit high sensitivity and selectivity for Hg2+ detection in aqueous solution. Interestingly, we found that the fluorescence of these Au NCs is stable either in a variety of complex matrixes or over a broad pH range (5.0-13.0) and therefore can be explored as a cell and animal imaging agent. More importantly, we demonstrated that the beta-lactoglobulin-stabilized Au NCs (beta-Lg-Au NCs) could serve as a sensor for the detection and quantification of Hg2+ in beverages, urine, and serum with high sensitivity. PMID- 27680747 TI - Ethnic Identity and Perceived Stress Among Ethnically Diverse Immigrants. AB - Recent empirical research suggests that having a strong ethnic identity may be associated with reduced perceived stress. However, the relationship between perceived stress and ethnic identity has not been tested in a large and ethnically diverse sample of immigrants. This study utilized a multi-group latent class analysis of ethnic identity on a sample of first and second generation immigrants (N = 1603), to determine ethnic identity classifications, and their relation to perceived stress. A 4-class ethnic identity structure best fit the data for this immigrant sample, and the proportion within each class varied by ethnicity, but not immigrant generation. High ethnic identity was found to be protective against perceived stress, and this finding was invariant across ethnicity. This study extends the findings of previous research on the protective effect of ethnic identity against perceived stress to immigrant populations of diverse ethnic origins. PMID- 27680746 TI - Associations Between Objective and Self-Report Measures of Traffic and Crime Safety in Latino Parents of Preschool Children. AB - Differences in subjective and objective safety may be explained by moderators that shape parental perceptions of the environment. This study examined associations between subjective and objective measures of traffic and crime safety in preschool parents (N = 240) and potential moderators. Community cohesion, social control, and physical activity parenting practices were measured. Objective measures of crime and traffic were measured at the block group level. Linear models revealed perceived traffic was negatively associated with the traffic hazards (b = -0.03; 95 % CI: -0.05, -0.01; p = .041). Acculturation moderated the relationship between perceptions of disorder and crime (b = 0.001; 95 % CI: 0.000, 0.003; p = .044). Poor community cohesion moderated the relationship between perceptions of disorder and crime (b = 0.0015; 95 % CI: 0.0002, 0.0028; p = .028). Perceived traffic safety was associated with the traffic hazard index in parents of boys (b = -0.04; 95 % CI: -0.07, -0.01; p = .027). Acculturation and community cohesion can be used to align misperceptions of safety to actual safety to promote outdoor play. PMID- 27680749 TI - Identification of Pyrogallol in the Ethyl Acetate-Soluble Part of Coffee as the Main Contributor to Its Xanthine Oxidase Inhibitory Activity. AB - In this study, ethyl acetate-soluble parts of hot-water extracts from roasted coffee beans were found to demonstrate potent xanthine oxidase (XO) inhibition. The XO inhibitory activities and chlorogenic lactone contents (chlorogenic lactones have previously been identified as XO inhibitors in roast coffee) were measured for ethyl acetate-soluble parts prepared from coffee beans roasted to three different degrees. Although chlorogenic lactone contents decreased with higher degrees of roasting, the XO inhibitory activity did not decrease. These data led us to investigate new potent inhibitors present in these ethyl acetate soluble extracts. Repeated assay-guided purifications afforded a highly potent XO inhibitor, which was eluted before chlorogenic lactones via medium-pressure chromatography using an octadecylsilica gel column. The obtained inhibitor was identified as pyrogallol (1,2,3-trihydroxybenzene), which had an IC50 of 0.73 MUmol L-1, much stronger than that of other related polyphenolic compounds. Quantitative analysis of pyrogallol and chlorogenic lactones revealed that pyrogallol (at concentrations of 33.9 +/- 4.2 nmol mL-1 in light roast coffee and 39.4 +/- 3.9 nmol mL-1 in dark roast coffee) was the main XO inhibitor in hot water extracts of roasted coffee beans (i.e., drinking coffee). PMID- 27680748 TI - The natural history and management of brachial plexus birth palsy. AB - Brachial plexus birth palsy (BPBP) is an upper extremity paralysis that occurs due to traction injury of the brachial plexus during childbirth. Approximately 20 % of children with brachial plexus birth palsy will have residual neurologic deficits. These permanent and significant impacts on upper limb function continue to spur interest in optimizing the management of a problem with a highly variable natural history. BPBP is generally diagnosed on clinical examination and does not typically require cross-sectional imaging. Physical examination is also the best modality to determine candidates for microsurgical reconstruction of the brachial plexus. The key finding on physical examination that determines need for microsurgery is recovery of antigravity elbow flexion by 3-6 months of age. When indicated, both microsurgery and secondary shoulder and elbow procedures are effective and can substantially improve functional outcomes. These procedures include nerve transfers and nerve grafting in infants and secondary procedures in children, such as botulinum toxin injection, shoulder tendon transfers, and humeral derotational osteotomy. PMID- 27680753 TI - Modulation of the transducer function of Na+,K+-ATPase: new mechanism of heart remodeling. AB - Endogenous digitalis-like factors were found in the mammalian and human blood. It was the starting point for the elucidation of the new non-pumping function of the Na+,K+-ATPase. It was previously well known that Na+,K+-ATPase is a pharmacological target receptor for cardiac glycosides (J.C. Skou. 1957. Biochim. Biophys. Acta, 23: 394-401). We have investigated the trophotropic effects of such agents as ouabain, epinephrine, norepinephrine, atenolol, and comenic acid using the organotypic tissue culture combined with the reconstruction of optical cross sections and confocal microscopy. It was shown that the growth zone of organotypic culture forms a multidimensional structure. Our results indicate that the cardiac glycoside ouabain applied in endogenous concentrations (10-8, 10-10 mol/L) can modulate transducer function of Na+,K+-ATPase and control the cell growth and proliferation. It was also shown that Src-kinase is involved in "endogenous" ouabain activated intracellular pathways as a series unit. Epinephrine (10-9-10-14 mol/L) and comenic acid (10-6-10-10 mol/L) were demonstrated to modulate the growth of 10- to 12-day-old chicken embryo cardiac tissue explants in a dose-dependent manner. Epinephrine and comenic acid regulate growth and proliferation of the cardiac tissue via receptor-mediated modulation Na+,K+-ATPase as a signal transducer. The trophotropic effects of the investigated agents specifically control the heart remodeling phenomenon. PMID- 27680752 TI - Nonalcoholic fatty liver disease: one entity, multiple impacts on liver health. AB - Nonalcoholic fatty liver disease (NAFLD) is very prevalent and now considered the most common cause of chronic liver disease. Staging the severity of liver damage is very important because the prognosis of NAFLD is highly variable. The long term prognosis of patients with NAFLD remains incompletely elucidated. Even though the annual fibrosis progression rate is significantly higher in patients with nonalcoholic hepatitis (NASH), both types of NAFLD (nonalcoholic fatty liver and nonalcoholic steatohepatitis) can lead to fibrosis. The risk for progressive liver damage and poor outcomes is assessed by staging the severity of liver injury and liver fibrosis. Algorithms (scores) that incorporate various standard clinical and laboratory parameters alongside imaging-based approaches that assess liver stiffness are helpful in predicting advanced fibrosis. PMID- 27680750 TI - Computerised navigation of unicondylar knee prostheses: from primary implantation to revision to total knee arthroplasty. AB - AIM: Computerized navigation of unicondylar knee arthroplasties (UKA) is not a widespread technique. The lifespan of a UKA depends on the quality of its implantation. We know that overcorrection leads to a rapid extension of the osteoarthritis to the opposite side of the knee and undercorrection to a rapid loosening or wear of the prosthesis. Because of these difficulties and following a long experience with navigation of total knee arthroplasties (TKA) and osteotomies around the knee, we began using navigation for revisions to TKA in 2003 and for UKAs in 2008. The aim of this work is to present, firstly, the axial alignment of 79 medial and 19 lateral computer-assisted UKAs and, secondly, the axial alignment of 23 computer-assisted UKA revisions to TKA. METHODS: In all the cases we used the Orthopilot(r) device (BBraun-Aesculap, Tuttlingen, Germany), which is a non image-based navigation system. RESULTS: For medial prostheses, the main objective was to obtain a post-operative HKA angle of 177 degrees +/- 2 degrees , i.e. an under correction of 1-5 degrees . This objective was met in 88.5 % of the cases. For lateral prostheses, the main objective was to achieve a post-operative HKA angle of 183 degrees +/- 2 degrees , i.e. also an under correction of 1-5 degrees . This objective was met in 84 % of the cases (3 cases at 186 degrees and no cases of over correction). Regarding UKA revisions, the main objective was to ensure an HKA angle of 180 degrees +/- 3 degrees . This was met in 92.4 % of the cases. CONCLUSION: As for TKA and osteotomies, computerized navigation of UKAs and UKA revisions allows the pre-operative goal to be met easily. PMID- 27680751 TI - Discriminative ability of calcaneal quantitative ultrasound compared with dual energy X-ray absorptiometry in men with hip or distal forearm fractures. AB - OBJECTIVES: The aim of this case-control study was to compare the discriminatory ability of bone mineral density (BMD) measurements and calcaneal quantitative ultrasound (QUS) parameters for fractures and to determine fracture thresholds for each variable in men with hip or distal forearm fractures. PATIENTS AND METHODS: A total of 20 men with hip and 18 men with distal forearm fractures and 38 age-matched controls were included in this study. Dual-energy X-ray absorptiometry (DXA) BMD (spine and hip) and calcaneal QUS measurements were made. Area under the curves (AUCs) were calculated to assess fracture discriminatory power of DXA and QUS variables. RESULTS: Quantitative Ultrasound Index (QUI) T-score and Speed of Sound (SOS) were found to be the best parameters for the identification of hip and distal forearm fractures, respectively, with AUCs greater than those of DXA BMD and other QUS parameters. While a QUI T-score of <=-1.18 could identify and rule out hip fracture cases with approximately 80% sensitivity and specificity, a SOS value of <=1529.75 reached to almost 90% for ruling in and out distal forearm fractures. CONCLUSION: The discriminatory performance of calcaneal QUS variables between fractured and non-fractured men was as good as those of the DXA BMD and even better. Since men appear to sustain fractures at closer QUS variable levels than those of the DXA BMD regardless of the fracture type, it may be speculated that calcaneal QUS may be more helpful in predicting the risk of fractures when BMD alone does not demonstrate impaired bones. LEVEL OF EVIDENCE: Level III, Study of Diagnostic Test. PMID- 27680754 TI - Alfred L. Goldberg: Probing the Proteasome. PMID- 27680755 TI - Prior opportunities to identify abuse in children with abusive head trauma. AB - Infants with minor abusive injuries are at risk for more serious abusive injury, including abusive head trauma (AHT). Our study objective was to determine if children with AHT had prior opportunities to detect abuse and to describe the opportunities. All AHT cases from 7/1/2009 to 12/31/2011 at four tertiary care children's hospitals were included. A prior opportunity was defined as prior evaluation by either a medical or child protective services (CPS) professional when the symptoms and/or referral could be consistent with abuse but the diagnosis was not made and/or an alternate explanation was given and accepted. Two-hundred-thirty-two children with AHT were identified; median age (IQR) was 5.40 (3.30, 14.60) months. Ten percent (22/232) died. Of the 232 patients diagnosed with AHT, 31% (n=73) had a total of 120 prior opportunities. Fifty-nine children (25%) had at least one prior opportunity to identify abuse in a medical setting, representing 98 prior opportunities. An additional 14 (6%) children had 22 prior opportunities through previous CPS involvement. There were no differences between those with and without a prior opportunity based on age, gender, race, insurance, mortality, or institution. Children with prior opportunities in a medical setting were more likely to have chronic subdural hemorrhage (48 vs. 17%, p<0.01) and healing fractures (31 vs. 19%, p=0.05). The most common prior opportunities included vomiting 31.6% (38/120), prior CPS contact 20% (24/120), and bruising 11.7% (14/120). Improvements in earlier recognition of AHT and subsequent intervention might prevent additional injuries and reduce mortality. PMID- 27680756 TI - Influence of Different Peritoneal Dialysis Fluids on the In Vitro Activity of Cefepime, Ciprofloxacin, Ertapenem, Meropenem and Tobramycin Against Escherichia Coli. AB - ? BACKGROUND: Peritonitis is a major problem among patients on peritoneal dialysis (PD). The influence of diverse PD fluids on the activity of frequently used antibiotics has been insufficiently investigated. Thus, the present study set out to investigate the impact of different PD fluids on the activity of cefepime, ciprofloxacin, ertapenem, meropenem, and tobramycin against Escherichia coli. ? METHODS: Time-kill curves in 4 different PD fluids (Dianeal PDG4, Extraneal, Nutrineal PD4 and Physioneal 40, all Baxter Healthcare Corp., Deerfield, IL, USA) were performed over 24 hours with 4 different concentrations (1 * minimum inhibitory concentration [MIC], 4 * MIC, 8 * MIC, 30 * MIC) of each antibiotic evaluated and without antibiotics as control. Cation-adjusted Mueller Hinton broth (CA-MHB) was used as comparator solution. ? RESULTS: In all PD fluids investigated, bacterial growth and antimicrobial activity of all antibiotics tested was significantly reduced compared with the CA-MHB comparator solution. Except at high concentrations of 30 * MIC, cefepime, ertapenem and meropenem demonstrated a strongly reduced activity in all PD fluids investigated. Ciprofloxacin and tobramycin were highly active and bactericidal in all PD fluids and demonstrated dose-dependent activity. ? CONCLUSION: The antimicrobial activity of cefepime, ertapenem and meropenem is limited or even nullified in certain PD fluids in vitro, whereas ciprofloxacin and tobramycin show excellent activity. The choice of PD fluids can impact the activity of antimicrobial agents and might influence microbiological outcome. Further studies are required to verify the clinical relevance of our findings. PMID- 27680757 TI - Association of Alternative Approaches to Normalizing Peritoneal Dialysis Clearance with Mortality and Technique Failure: A Retrospective Analysis Using the United States Renal Data System-Dialysis Morbidity and Mortality Study, Wave 2. AB - ? BACKGROUND: Total body water (V) is an imprecise metric for normalization of dialytic urea clearance (Kt). This poses a risk of early mortality/technique failure (TF). We examined differences in the distribution of peritoneal Kt/V when V was calculated with actual weight (AW), ideal weight (IW), and adjusted weight (ADW). We also examined the associations of these Kt/V measurements, Kt/body surface area (BSA), and non-normalized Kt with mortality and TF. ? METHODS: This is a retrospective cohort study of 534 incident peritoneal dialysis (PD) patients from the Dialysis Morbidity and Mortality Study Wave 2 linked with United States Renal Data System through 2010. Using Cox-proportional hazard models, we examined the relationship of several normalization strategies for peritoneal urea clearance, including Kt/VAW, Kt/VIW, Kt/VADW, Kt/BSA, and non-normalized Kt, with the outcomes of mortality and TF. Harrell's c-statistics were used to assess the relative predictive ability of clearance metrics for mortality and TF. The distributions of Kt/VAW, KT/VIW, and KT/VADW were compared within and between body mass index (BMI) strata. ? RESULTS: Median patient age: 59 (54% male; 72% white; 91% continuous ambulatory PD [CAPD]). Median 24-hour urine volume: 700 mL; median estimated glomerular filtration rate (eGFR) at initiation: 7.15 mL/min/1.73 m2. Technique failure and transplant-censored mortality at 5 years: 37%. Death and transplant-censored TF at 5 years: 60%. There were no significant differences in initial eGFR and 24-hour urine volume across BMI strata. There were statistically significant differences in each Kt/V calculation within the underweight, overweight, and obese strata. After adjustment, there were no significant differences in the hazard ratios (HRs) for TF/mortality for each clearance calculation. Harrell's c-statistics for mortality for each clearance calculation were 0.78, and for TF, 0.60 - 0.61. ? CONCLUSIONS: Peritoneal urea clearances are sensitive to subtle changes in the estimation of V. However, there were no detectable significant associations of Kt/VAW, Kt/VIW, Kt/VADW, Kt/BSA, or Kt with TF or mortality. PMID- 27680758 TI - The Phantom of Metformin-Induced Lactic Acidosis in End-Stage Renal Disease Patients: Time to Reconsider with Peritoneal Dialysis Treatment. AB - ? OBJECTIVE: Metformin continues to be the safest and most widely used antidiabetic drug. In spite of its well-known benefits; metformin use in end stage renal disease (ESRD) patients is still restricted. Little has been reported about the effect of peritoneal dialysis (PD) on metformin clearance and the phantom of lactic acidosis deprives ESRD patients from metformin therapeutic advantages. Peritoneal dialysis is probably a safeguard against lactic acidosis, and it is likely that using this drug would be feasible in this group of patients. ? MATERIAL AND METHODS: The study was conducted on 83 PD patients with type 2 diabetes mellitus. All patients were on automated PD (APD). Metformin was administered in a dose of 500 - 1,000 mg daily. Patients were monitored for glycemic control. Plasma lactic acid and plasma metformin levels were monitored on a scheduled basis. Peritoneal fluid metformin levels were measured. In addition, the relation between plasma metformin and plasma lactate was studied. ? RESULTS: Mean fasting blood sugar (FBS) was 10.9 +/- 0.5 and 7.8 +/- 0.7, and mean hemoglobin A1-C (HgA1C) was 8.2 +/- 0.8 and 6.4 +/- 1.1 at the beginning and end of the study, respectively (p < 0.001). The mean body mass index (BMI) was 29.1 +/- 4.1 and 27.3 +/- 4.5 at the beginning and at the end of the study, respectively (p < 0.001). The overall mean plasma lactate level across all blood samples was 1.44 +/- 0.6. Plasma levels between 2 and 3 mmol/L were found in 11.8% and levels of 3 - 3.6 mmol/L in 2.4% plasma samples. Hyperlactemia (level > 2 and <= 5 mmol/L) was not associated with overt acidemia. None of our patients had lactic acidosis (levels > 5 mmol/L). Age >= 60 was a predictor for hyperlactemia. No relationship was found between plasma metformin and lactate levels. ? CONCLUSION: Metformin may be used with caution in a particular group of ESRD patients who are on APD. Metformin allows better diabetic control with significant reduction of BMI. Information on the relationship between metformin and plasma lactate levels is lacking. Peritoneal dialysis appears to be a safeguard against the development of lactic acidosis in this group of patients. PMID- 27680759 TI - Home Dialysis Utilization Among Racial and Ethnic Minorities in the United States at the National, Regional, and State Level. AB - ? BACKGROUND: United States Renal Data System (USRDS) data from 2014 show that African Americans (AA) are underrepresented in the home dialysis population, with 6.4% versus 9.2% utilization in the general populace. This racial disparity may be inaccurately ascribed to the nation as a whole if regional and inter-state variability exists. This investigation sought to examine home dialysis utilization by minority Medicare beneficiary populations across the US nationally, regionally, and by individual state. ? METHODS: The 2012 Medicare 100% Outpatient Standard Analytic File was used to identify all Medicare fee-for service (FFS) patients, with state of residence and race, receiving an outpatient dialysis facility bill type. Peritoneal dialysis (PD) and home hemodialysis (HHD) patients were identified using revenue and condition codes and were defined by having at least one claim during the year that met criteria for the category. Beneficiaries were counted once for each modality used that year. A home dialysis utilization ratio (UR) was calculated as the ratio of the proportion of a minority on PD or HHD within a geographic division to the proportion of Caucasians on PD or HHD within the same geographic division. A UR less than 1.00 indicated under-representation while a UR over 1.00 indicated over representation. Utilization ratios were compared using a Poisson regression model. ? RESULTS: A total of 369,164 Medicare FFS dialysis patients were identified. Within the total cohort, AA were the most underrepresented minority on PD (UR 0.586; 95% confidence interval [CI]: 0.585 - 0.586; p < 0.0001), followed by Hispanics (UR 0.744; 95% CI 0.743 - 0.744; p < 0.0001). The underutilization of PD by AA and Hispanics could not be ascribed to any region of the US, as all regions of the US had UR < 1.00. Only Massachusetts had a UR > 1.00 for AA on PD. Peritoneal dialysis UR values for Asians and those self identified as Other were 0.954; 95% CI 0.953 - 0.954 and 0.932; 95% CI 0.931 - 0.932, respectively. Nationally, all minorities utilized HHD less than Caucasians. However, more variability existed, with Asians utilizing more HHD than Caucasians in the Midwest. ? CONCLUSIONS: Although regional and interstate variability exists, there is near universal under-representation of AA and Hispanics in the home dialysis population, while Asians and Other demonstrate more interregional and interstate variability. PMID- 27680760 TI - Pharmacokinetics of Intraperitoneal Daptomycin in Patients with Peritoneal Dialysis-Related Peritonitis. AB - ? BACKGROUND: Antibiotics are preferentially delivered via the peritoneal route to treat peritoneal dialysis-related peritonitis (PDRP) to ensure that maximal concentrations are delivered to the site of infection. Our study focused on the pharmacokinetics of daptomycin (DAP) administered via the intraperitoneal (IP) route in patients with PDRP. ? METHODS: According to the DaptoDP protocol (Clinical Trial No. 2012-005699-33), IP DAP was administered daily, i.e., during the 6-h Nutrineal (Baxter Healthcare Corporation, Deerfield, IL, USA) dwell time period, for 14 days, in addition to administration of the antibiotics used for the usual care of patients with PDRP. The plasma and IP levels of DAP were measured on days 1 and 5. The tested dose was 200 mg/day. The principal endpoint was the dialysate concentration after 6 hours of dwell time > 16 mg/L (corresponding to 4 x minimum inhibitory concentration [MIC] for E. faecalis). ? RESULTS: Three participants were evaluated. On day 5, the IP concentrations after 6 hours of dwell time were between 6.3 and 23.4 mg/L, and the peak plasma concentrations were between 13.0 and 15.3 mg/L. ? CONCLUSION: The results suggest that 200 mg/day is very likely sufficient for the treatment of PDRP by Staphylococci or Streptococci whereas it could be insufficient to treat PRDP by Enterococci. The good peritoneal bioavailability of DAP was quantitatively established, suggesting that IP administration could also be used as an alternate route for patients with damaged venous access. No DAP accumulation that could lead to toxic concentrations after repeated administration is expected, even in anuric patients. The protocol will further continue to assess whether a higher dose achieves the pharmacokinetic objectives. PMID- 27680761 TI - Psychosocial Factors Predict Nonadherence to PD Treatment: A Hong Kong Survey. AB - ? BACKGROUND: Nonadherence to hand hygiene and aseptic regimen, dialysis environment guidelines, and catheter and exit-site care guidelines are risk factors of peritonitis. However, little is known about the psychosocial factors that account for the nonadherent behavior of patients undergoing peritoneal dialysis (PD). Applying the health belief model, this study seeks to enhance the understanding of psychosocial influences on patients' nonadherent behavior to the 3 regimen components. ? METHODS: Through referrals by 7 Hong Kong renal patient support groups, we surveyed patients undergoing PD treatment. ? RESULTS: A total of 244 Hong Kong PD patients completed the questionnaires. About 90% of the patients reported no deviation from catheter and exit-site care guidelines. However, the nonadherence rates of hand hygiene and aseptic regimen and of dialysis environment guidelines were 30.3% and 23%, respectively. Longer time on PD treatment and lower family monthly income were associated with nonadherence to dialysis environment guidelines. Employed patients tended toward nonadherence to catheter and exit-site care guidelines twice as much as unemployed patients. Of the 5 health beliefs, perceived benefits, perceived barriers, and efficacy belief were significant predictors of nonadherence to the 3 regimen components. ? CONCLUSIONS: The findings of this study inform the design of intervention to change patients' behavior in regimen nonadherence for preventing peritonitis. To identify the target audience for adherence intervention based on the 3 regimen components, the results suggest dividing patients into subgroups according to their sociodemographic background. To foster behavioral change, health communicators should address patients' health beliefs when formulating intervention strategies. PMID- 27680762 TI - Economic Impact of a Peritoneal Dialysis Continuous Quality Improvement Program in Colombia. AB - ? BACKGROUND: There is little information regarding the financial burden of peritonitis and the economic impact of continuous quality improvement (CQI) programs in peritoneal dialysis (PD) patients. The objectives of this study were to measure the costs of peritonitis, and determine the net savings of a PD CQI program in Colombia. ? METHODS: The Renal Therapy Services (RTS) network in Colombia, along with Coomeva EPS, provided healthcare resource utilization data for PD patients with and without peritonitis between January 2012 and December 2013. Propensity score matching and regression analysis were performed to estimate the incremental cost of peritonitis. Patient months at risk, episodes of peritonitis pre- and post-CQI, and costs of CQI were obtained. Annual net savings of the CQI program were estimated based on the number of peritonitis events prevented. ? RESULTS: The incremental cost of a peritonitis episode was $250. In an 8-year period, peritonitis decreased from 1,837 episodes per 38,596 patient months in 2006 to 841 episodes per 50,910 patient-months in 2014. Overall, the CQI program prevented an estimated 10,409 episodes of peritonitis. The cost of implementing the CQI program was $147,000 in the first year and $119,000 annually thereafter. Using a five percent discount rate, the net present value of the program was $1,346,431, with an average annual net savings of $207,027. The return on investment (i.e. total savings-program cost/program cost) of CQI was 169%. ? CONCLUSION: Continuous quality improvement initiatives designed to reduce rates of peritonitis have a strong potential to generate cost savings. PMID- 27680763 TI - Clinical Outcomes of Peritoneal Dialysis in End-Stage Renal Disease Patients with Liver Cirrhosis: A Propensity Score Matching Study. AB - ? BACKGROUND: Clinical results of long-term peritoneal dialysis (PD) therapy in patients with liver cirrhosis (LC) and end-stage renal disease (ESRD) are controversial. This study evaluated the clinical outcomes of LC patients undergoing PD. ? METHODS: Clinical records were retrospectively collected from a single center between January 2007 and December 2014. An analysis of PD patients with LC and without liver disease was performed using propensity score matching. We further restricted matching by age, gender, and the presence of diabetes mellitus. Two cohorts of 33 patients each were selected. Early technical complications were defined as the presence of catheter-related complications, including malposition, leakage, omental wrapping, obstruction, and requiring a transfer to hemodialysis (HD) within 6 months of initiating PD. ? RESULTS: Mean PD duration was lower in LC patients (57.2 +/- 46.1 months) than in controls (85.8 +/- 64.2 months). Blood urea nitrogen, creatinine, and albumin levels were significantly lower in LC patients than in the control group. Cystatin C and cystatin C-based glomerular filtration rates were not significantly different in the LC group compared with those in the controls. We found that the risks for early technical complications, peritonitis, and long-term PD and patient survival were not higher in patients with LC than in those without LC. Ascites were easily controlled, and hepatic encephalopathy did not affect PD maintenance in LC patients. ? CONCLUSIONS: The clinical outcomes, including technical complications, peritonitis, and patients' survival, suggest that PD can be used as a renal replacement therapy in ESRD patients with LC. PMID- 27680764 TI - Epidemiology and Clinical Characteristics of Acinetobacter Peritoneal Dialysis Related Peritonitis in Hong Kong-With a Perspective on Multi-Drug and Carbapenem Resistance. AB - ? BACKGROUND: Acinetobacter spp. is an important cause of peritoneal dialysis (PD)-related peritonitis, but studies on Acinetobacter peritonitis have been scarce. In view of the rising concern of carbapenem-resistant Acinetobacter (CRA) and multidrug-resistant Acinetobacter (MDRA) infections, we conducted this study on the incidence of Acinetobacter peritonitis and the impact of CRA and MDRA on its outcome. ? METHODS: We retrospectively evaluated the clinical characteristics, prevalence, antibiotic sensitivity patterns, outcomes, and factors associated with treatment failure over the past 16 years in our patients with Acinetobacter PD-related peritonitis. ? RESULTS: Out of 2,389 episodes of peritonitis, there were 66 episodes (3%) of Acinetobacter peritonitis occurring in 59 patients. Twelve episodes were caused by MDRA (18%), of which 5 were CRA (8%). There was a progressive increase in the incidence of MDRA and CRA infections over the study period. Most isolates were sensitive to sulbactam combinations (ampicillin-sulbactam [95.4%] and cefoperazone-sulbactam [93.9%]), aminoglycosides (amikacin [92.4%], tobramycin [90.9%], and gentamicin [89.4%]), and carbapenems (imipenem [92.2%]). There was 1 case of relapse. Fifteen episodes resulted in catheter removal (23%), and 7 patients died (11%). Hypoalbuminemia (odds ratio [OR] = 0.85, p = 0.006) and carbapenem resistance (OR = 18.2, p = 0.049) were significantly associated with higher rates of treatment failure. ? CONCLUSION: Both carbapenem resistance and hypoalbuminemia were significantly associated with treatment failure. Up to 80% of peritonitis episodes by CRA resulted in catheter loss or mortality. Sulbactam combinations and/or aminoglycosides remained effective for the majority of Acinetobacter isolates. There seemed to be an increasing relative incidence of MDRA and CRA infections over the past 16 years. PMID- 27680765 TI - Introduction of Renal Key Performance Indicators Associated with Increased Uptake of Peritoneal Dialysis in a Publicly Funded Health Service. AB - ? BACKGROUND: Increased demand for treatment of end-stage kidney disease has largely been accommodated by a costly increase in satellite hemodialysis (SHD) in most jurisdictions. In the Australian State of Victoria, a marked regional variation in the uptake of home-based dialysis suggests that use of home therapies could be increased as an alternative to SHD. An earlier strategy based solely on increased remuneration had failed to increase uptake of home therapies. Therefore, the public dialysis funder adopted the incidence and prevalence of home-based dialysis therapies as a key performance indicator (KPI) for its health services to encourage greater uptake of home therapies. ? METHODS: A KPI data collection and bench-marking program was established in 2012 by the Victorian Department of Health and Human Services, with data provided monthly by all renal units in Victoria using a purpose-designed website portal. A KPI Working Group was responsible for analyzing data each quarter and ensuring indicators remained accurate and relevant and each KPI had clear definitions and targets. We present a prospective, observational study of all dialysis patients in Victoria over a 4 year period following the introduction of the renal KPI program, with descriptive analyses to evaluate the proportion of patients using home therapies as well as home dialysis modality survival. ? RESULTS: Following the introduction of the KPI program, the net growth of dialysis patient numbers in Victoria remained stable over 4 years, at 75 - 80 per year (approximately 4%). However, unlike the previous decade, about 40% of this growth was through an increase in home dialysis, which was almost exclusively peritoneal dialysis (PD). The increase was identified particularly in the young (20 - 49) and the elderly (> 80). Disappointingly, however, 67% of these incident patients ceased PD within 2 years of commencement, 46% of whom transferred to SHD. ? CONCLUSIONS: Introduction of a KPI program was associated with an increased uptake of PD but not home HD. This change in clinical practice restricted growth of SHD and reduced pressure on satellite services. The effect was offset by a modest PD technique survival. Many patients in whom PD was unsuccessful were subsequently transferred to SHD rather than home HD. PMID- 27680767 TI - Precipitation of Carbamazepine-Controlled Seizures Due to Low-Dose Risperidone in a Child: A Conspiracy to Unbalance Blood Electrolytes. PMID- 27680766 TI - Patients' Perspectives on the Prevention and Treatment of Peritonitis in Peritoneal Dialysis: A Semi-Structured Interview Study. AB - ? BACKGROUND: Peritoneal dialysis (PD) is recommended for adults with residual kidney function and without significant comorbidities. However, peritonitis is a serious and common complication that is associated with hospitalization, pain, catheter loss, and death. This study aims to describe the beliefs, needs, and experiences of PD patients about peritonitis, to inform the training, support, and care of these patients. ? METHODS: Qualitative semi-structured interviews were conducted with 29 patients from 3 renal units in Australia who had previous or current experience of PD. The interviews were conducted between November 2014 and November 2015. Transcripts were analyzed thematically. ? RESULTS: We identified 4 themes: constant vigilance for prevention (conscious of vulnerability, sharing responsibility with family, demanding attention to detail, ambiguity of detecting infection, ineradicable inhabitation, jeopardizing PD success); invading harm (life-threatening, wreaking internal damage, debilitating pain, losing control and dignity); incapacitating lifestyle interference (financial strain, isolation and separation, exacerbating burden on family); and exasperation with hospitalization (dread of hospital admission, exposure to infection, gruelling follow-up schedule, exposure to harm). ? CONCLUSIONS: Patients perceived that peritonitis could threaten their health, treatment modality, and lifestyle, which motivated vigilance and attention to hygiene. They felt a loss of control due to debilitating symptoms including pain and having to be hospitalized, and they were uncertain about how to monitor for signs of peritonitis. Providing patients with education about the causes and signs of peritonitis and addressing their concerns about lifestyle impact, financial impact, hospitalization, and peritonitis-related anxieties may improve treatment satisfaction and outcomes for patients requiring PD. PMID- 27680768 TI - Introduction to BMJ Rapid Recommendations. PMID- 27680769 TI - Factors Affecting the Quality of Anticoagulation With Vitamin K Antagonists in Venous Thromboembolism Patients. AB - INTRODUCTION: Treatment of venous thromboembolism (VTE) is classically based on oral vitamin K antagonists (VKAs). Due to the disadvantages and side effects of these drugs, monitoring the quality of anticoagulation by assessing time within therapeutic range (TTR) is recommended. Variables altering the TTR in patients with VTE are yet to be determined. The aim of this study was to analyze the quality of anticoagulation in patients with VTE treated with VKAs and to identify factors associated with poor-quality anticoagulation. METHODS: A retrospective observational study was performed in a cohort of 94 patients diagnosed with VTE undergoing treatment with VKAs. The TTR at 6 months was analyzed by the Rosendaal method. Univariate and a multivariate logistic regression analyses were performed to unravel factors that increase risk of poor-quality anticoagulation. RESULTS: The TTR at 6 months in this cohort was 60.5%; 54 patients had a TTR < 65%. In the univariate analysis, female sex, age >= 65 years, and renal impairment were significantly associated with poor-quality anticoagulation. However, in the multivariate logistic regression model, only renal impairment was independently associated with poor-quality anticoagulation (odds ratio = 3.31, 95% confidence interval [1.049, 10.486], p = .041). DISCUSSION: The average quality of anticoagulation was 60.5%, and a high percentage of patients had a quality of anticoagulation below recommended levels. Study findings indicate that renal impairment is an independent risk factor for poor-quality anticoagulation in patients with VTE treated with VKAs. PMID- 27680770 TI - Chevalone C analogues and globoscinic acid derivatives from the fungus Neosartorya spinosa KKU-1NK1. AB - Four meroterpenoids, 1-hydroxychevalone C, 1-acetoxychevalone C, 1,11 dihydroxychevalone C, and 11-hydroxychevalone C and two ester epimers, 2S,4S spinosate and 2S,4R-spinosate, together with seven known compounds, chevalones B, C, and E, tryptoquivaline, nortryptoquivaline, tryptoquivaline L, and quinadoline A were isolated from the fungus Neosartorya spinosa. Their structures were established based on spectroscopic data analyses. The theoretical ECD spectra of epimers, 2S,4S-spinosate and 2S,4R-spinosate were calculated to support the experimental results of their CD spectra. 1-hydroxychevalone C exhibited antimycobacterial activity against Mycobacterium tuberculosis with a MIC value of 26.4 MUM. 1-Acetoxychevalone C and tryptoquivaline showed antimalarial activity against Plasmodium falciparum with IC50 values of 6.67 and 2.65 MUM, respectively. In addition, 1-hydroxychevalone C, 1-acetoxychevalone C, 1,11 dihydroxychevalone C and quinadoline A showed cytotoxicity against KB and NCI H187 cancer cell lines with IC50 values in the range of 32.7-103.3 MUM. PMID- 27680771 TI - Gender impacts on the correlations between nonalcoholic fatty liver disease and hypertension in a Chinese population aged 45-60 y. AB - : No previous study has reported the association between nonalcoholic fatty liver disease (NAFLD) and the risk of hypertension in the Chinese population. Therefore, the aim of this study was to evaluate the relationship between NAFLD and hypertension in a middle-aged Chinese population. The study subject was (a group of) 1006 Chinese adults aged 45-60 y in Shandong Province who participated in the Weifang Nutrition and Health Survey (2014-2015). Hypertension was defined as systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >= 9 0mmHg. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in women), no use of steatogenic medications within the past six months, no exposure to hepatotoxins, and no history of bariatric surgery. All anthropometric measurements and biochemical data were collected following standard protocols. Multivariate logistic regression analysis was used to identify the association between NAFLD and hypertension with adjustment of potential confounding variables. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting glucose, SBP, DBP, triglycerides (TG), serum uric acid (SUA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the prevalence of hypertension and NAFLD were significantly higher in males than in females (p < 0.05). Females had significantly higher levels of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). After adjusting for potential confounders, NAFLD was associated with an increased risk of hypertension in both male and female, with odds ratios (ORs) (95% CI) of 2.152 (1.324-3.498) and 2.133 (1.409-3.229), respectively. CONCLUSIONS: Our findings indicated that NAFLD was significantly associated with the risk of hypertension in males than in females. However, our findings also need to be confirmed in future prospective studies. ABBREVIATIONS: BMI: body mass index; WC: waist circumference; WHR: waist-hip ratio; SBP: systolic blood pressure; DBP: diastolic blood pressure; FG: fasting glucose; TG: triglycerides; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; SUA: serum uric acid; NAFLD: nonalcoholic fatty liver disease; LDL-C: low-density lipoprotein cholesterol; OR: odds ratio; CI: confidence interval; ALT: alanine aminotransferase; AST: aspartate aminotransferase. PMID- 27680772 TI - Genetic diagnosis of familial hypercholesterolaemia using a rapid biochip array assay for 40 common LDLR, APOB and PCSK9 mutations. AB - BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) leads to a lifelong increase in plasma LDL levels with subsequent increase in premature vascular disease. Early diagnosis and treatment is the key to effective management of this condition. This research aims to produce a simple and cost effective genetic test which could identify the majority (71%) of mutations causing FH in the UK and Ireland. METHODS: The Randox Biochip Array Technology was used to detect 40 point mutations in LDLR, APOB and PCSK9 genes, over two 5 * 5 arrays. This technology uses multiplex allele specific PCR and biochip array hybridisation, followed by a chemiluminescence detection system and software for automated mutation calling. RESULTS: The FH biochip array assay was validated in the Belfast Genetics Laboratory using 199 cascade screening samples previously sequenced for known FH causing family mutations, the overall sensitivity was 98%. The assay was then used for routine testing of 663 patients with possible FH, from clinics across the UK and Ireland. A total of 49 (7.4%) mutation positive individuals were identified, however, for the clinics in England the detection rate was 12.9%. Further analysis of 120 biochip negative patients, using DNA sequencing, did not identify any false negatives. CONCLUSIONS: The FH biochip array provides a rapid and reliable genetic test for the majority of FH causing point mutations in the UK and Ireland. A total of 32 samples can be run in 3 h. This allows clinics to evaluate additional patients for a possible diagnosis of FH such as patients with high LDL, patients with early onset coronary disease, and patients with relatives known to have FH. PMID- 27680773 TI - Parity, coronary heart disease and mortality in the old order Amish. AB - BACKGROUND AND AIMS: Prior data on the association between parity and mortality are limited by the presence of sociodemographic confounders including cultural norms of parity. Our objective was to determine the association between parity and mortality in the Amish, a socioeconomically homogenous group with large numbers of children per family. METHODS: We conducted a population-based cohort study among 518 Old Order Amish women enrolled in a cardiovascular awareness program. The mean length of follow-up for mortality was 13.52 years. We determined the adjusted associations between parity and obesity, prevalent coronary heart disease and mortality. RESULTS: The mean number of total births per woman was 6.7 +/- 3.6 with a mode of 8. No significant association was observed between parity and all-cause mortality when adjusted for age (HR 1.00 per additional birth; 95% CI 0.96-1.05; p = 0.85) or in multivariate analysis (HR 1.00, 95% CI 0.95-1.05; p = 0.95). There was also no association of parity in age or multivariable adjusted models with prevalent diabetes, hypertension or coronary heart disease. Despite the lack of effect of parity on mortality, a significant association of ten or more births was observed with higher body mass index (BMI) compared to the referent group of 8-9 total births. CONCLUSIONS: In a highly homogeneous population with high rates of parity, no association between overall mortality and parity was observed. Ten or more births were significantly associated with a higher BMI but not with overall mortality. PMID- 27680774 TI - Plasma cystatin C and neutrophil gelatinase-associated lipocalin in relation to coronary atherosclerosis on intravascular ultrasound and cardiovascular outcome: Impact of kidney function (ATHEROREMO-IVUS study). AB - BACKGROUND AND AIMS: We investigated whether plasma cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) are associated with intravascular ultrasound (IVUS)-derived characteristics of coronary atherosclerosis and 1-year adverse coronary events in patients with normal and mildly-to-moderately impaired kidney function. METHODS: Between 2008 and 2011, virtual histology (VH)-IVUS of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography. Creatinine, CysC and NGAL were measured in pre-procedural blood samples. Presence of VH-IVUS-derived thin-cap fibroatheroma (TCFA) lesions, lesions with plaque burden (PB)>=70% and lesions with minimal luminal area (MLA)<=4 mm2 was assessed. Major adverse coronary events (MACE) comprised the composite of all-cause mortality, acute coronary syndrome, or unplanned coronary revascularization. Analyses were stratified using eGFRCr of 90 ml/min/1.73 m2 as the cut-off. RESULTS: In patients with normal kidney function, those with higher CysC levels had fewer lesions with PB >= 70% and fewer VH-TCFA lesions (adjusted odds ratios (ORs) and 95% confidence intervals (CIs): 0.46 [0.30-0.69] and 0.59 [0.44-0.83], respectively, per standard deviation (SD) ln[ng/mL] CysC). Those with higher NGAL levels also had fewer lesions with PB >= 70% (adjusted OR [95% CI]:0.49 [0.29-0.82]) In patients with impaired kidneys, no differences in high-risk lesions were observed for CysC or NGAL. However, those with higher CysC had higher risk of MACE (hazard ratio (HR):1.4, 95% CI [1.03-1.92]). This was not the case in patients with normal kidney function. NGAL did not influence risk of MACE. CONCLUSIONS: Mild-to moderate kidney dysfunction modifies the relationship between CysC and high-risk coronary lesions. This has not been established before, and offers an explanation for the difference in findings between experimental and epidemiologic studies. PMID- 27680775 TI - Serum interleukin 6 and 10 levels in Takotsubo cardiomyopathy: Increased admission levels may predict adverse events at follow-up. AB - BACKGROUND AND AIMS: Systemic inflammation has been hypothesized as a possible mechanism of Takotsubo cardiomyopathy (TTC). Aim of the study was to assess the role of interleukin (IL)-6 and IL-10 in subjects with an episode of TTC. METHODS: Fifty-six consecutive subjects with TTC were prospectively enrolled in the study and followed for a mean of 178 days. Circulating levels of IL-6, IL-10, clinical condition and left ventricular ejection fraction were evaluated at admission. Incidence of death, re-hospitalization and recurrence of TTC during follow-up was also recorded. RESULTS: 23% of patients experienced in-hospital complications while 20% of patients had adverse events at follow-up. IL-6 and IL-10 serum levels at admission were higher in subjects with adverse events at follow-up (120 +/- 294 vs. 22 +/- 40 pg/ml, p<0.05; 13 +/- 35 vs. 2 +/- 3 pg/ml, p=0.05, respectively). Increased serum levels of IL-6 and IL-10 were associated with higher adverse events rates at follow-up (Log-Rank p<0.001, <0.05, hazard ratio 8.6, 5.1, respectively) and mortality rates (Log-Rank p<0.001, p<0.05, hazard ratio 20.8, 7.1, respectively). Subjects with both increased IL-6 and IL-10 levels were characterized by an increased risk of adverse events when compared to subjects with only IL-6 or IL-10 increased levels or with values below cutoff values (Log-Rank p<0.01 for any event, <0.001 for death; hazard ratio 1.20 for any event, 1.31 for death), even after correction for age, LVEF and NTproBNP levels in multivariable Cox analysis. CONCLUSIONS: Serum IL-6 and IL-10 admission levels are associated with higher risk of adverse events during follow-up. PMID- 27680777 TI - Predicting 30-Day Readmission or Death in Heart Failure-Reply: Looking Beyond the C- Statistic. PMID- 27680778 TI - COMPLICATED CONGENITAL RETINOSCHISIS. AB - PURPOSE: To describe the treatment and natural history of a patient with complicated congenital retinoschisis. METHODS: A retrospective case report. A 10 month-old boy with congenital retinoschisis presented with tractional retinal detachments and foveal schisis in both eyes. RESULTS: On presentation, vision was decreased in both eyes with presumed amblyopia of the left eye. Funduscopic examination revealed bilateral foveal schisis and tractional retinal detachment involving the macula. Follow-up examination revealed superior retinal dragging and peripheral ischemia on fluorescein angiogram in both eyes. Nine months after presentation, combined rhegmatogenous and tractional retinal detachment developed in the right eye and was treated by scleral buckle. After vitrectomy for nonclearing vitreous hemorrhage in the left eye, a combined rhegmatogenous and tractional retinal detachment developed. Vitrectomy and lensectomy with silicone oil was performed. At 6 years of follow-up, both retinas were attached and foveal schisis had resolved. CONCLUSION: Sight threatening complications of congenital retinoschisis include retinal detachment and vitreous hemorrhage. Vitrectomy and/or scleral buckling may prevent progression of vision loss and promote resolution of schisis. PMID- 27680776 TI - Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis. AB - Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. PMID- 27680779 TI - Risk factors following first spontaneous epileptic seizure in children below 3 years of age. AB - AIM OF THE STUDY: To assess the recurrence rate after the first spontaneous epileptic seizure in pediatric patients, and determine the related risk factors. MATERIALS AND METHODS: Data from 190 infants (aged between one month and three years) admitted after first spontaneous epileptic seizure to Soochow University Affiliated Children's Hospital between April 2009 and April 2011 were retrospectively analyzed; patients were followed up until April 2014. The recurrence rate and risk factors of recurrence were analyzed based on central nervous system imaging data (computed tomography or magnetic resonance imaging), electroencephalogram (EEG) and developmental quotient assessment. RESULTS: Of the 190 infants, 11 cases (5.79%) were lost to follow-up. The cumulative recurrence rate of spontaneous epileptic seizure after five years was 52%. A total of 82% recurrence cases occurred within the first year. Age > 24 months (odds ratio (OR) = 0.498?95% confidence interval (CI): 0.285-0.869) was an independent protective factor, while symptomatic seizure (OR = 1.624, 95% CI: 1.020-2.587), seizure during sleep (OR = 2.779, 95% CI: 1.757-4.397) and epileptic discharge in EEG (OR=3.269, 95% CI: 2.049-5.217) were independent risk factors. CONCLUSION: Recurrence rate is high in infants after the first spontaneous epileptic seizure, and recurrence is more likely to occur within one year. PMID- 27680781 TI - Nonhealing Lower Leg Ulcers. PMID- 27680780 TI - Cholinergic Changes in Aging and Alzheimer Disease: An [18F]-F-A-85380 Exploratory PET Study. AB - The central cholinergic system undergoes changes during the physiological process of aging and the pathologic process of Alzheimer disease (AD). We aimed to analyze the impairment of cholinergic pathways by positron emission tomography using the [F]-F-A-85380 (FA85) tracer, which has a high affinity for nicotinic acetylcholine receptors (nAChRs). Aging was assessed by comparing young (n=10) and elderly (n=4) healthy subjects, and the pathologic process of AD was assessed by comparing elderly controls and age-matched AD patients (n=8). We measured an index of the nAChR density in the cortex and the hippocampus and the total number of FA85-binding sites by taking into account the volume changes. In AD, the nAChR density was preserved in both the cortex and hippocampus. The total estimated number of FA85-binding sites was decreased in the hippocampus despite the lack of a significant loss of volume, whereas the difference in the cortex did not withstand the adjustment for multiple comparisons despite a significant loss of volume. In contrast, in aging, the estimated number of FA85-binding sites was decreased in both the cortex and hippocampus with significant hippocampal atrophy. These findings suggest a preferential impairment of cholinergic pathways in the cortex during aging, whereas in AD, this damage predominated in the hippocampus with a potential compensatory cholinergic effect in the cortex. PMID- 27680782 TI - A new strategy in sclerotherapy of varicose veins. AB - AIM: The aim of our study was to evaluate the efficacy of a new method of compression sclerotherapy of GSV and SSV. MATERIALS AND METHODS: 345 lower extremities with primary varicose veins, with a long reflux of the GSV (C2-6; Ep; As 2, 3; +/- p; Pr), have been submitted to sclerotherapy applying the following method: injection of foam (Polidocanol 2%), or liquid sclerosant (iodate solution 4-6% or Polodocanol 3%) in the trunk of the GSV; echoguided compression of sapheno-femoral junction (performed using an inflatable device, the Safeguard); immediate eccentric positive compression on the trunk of the GSV; and short elastic bandage. RESULTS: The results have shown that applying this method of sclerotherapy the failure rate decreases, independently to physical form of sclerosing agent. CONCLUSIONS: The use of Safeguard(r) interrupts reflux to the lower veins, and these can so be well sclerosed and compressed with short elastic bandage. KEY WORDS: Long compression, Foam, Saphenous vein Sclerotherapy varicose veins. PMID- 27680823 TI - Editorial. AB - Thousands of nurses and other health service workers joined last week's day of action, making it the biggest demonstration yet in the six-week pay campaign. The day was a huge success in media terms. Regardless of political persuasion, most national and regional newspapers carried photographs and stories about nurses who had given up their lunchtime to protest at this year's pay award. And while the media and public were given a flavour of nurses' strength of feeling, politicians - many of whom have received RCN pay campaign postcards - packed the House of Commons to hear opposition leader Tony Blair question the Prime Minister about the unfairness of local pay. Blair pressed home the point that regional disparity would result in one nurse being paid less than a colleague in a neighbouring hospital doing the same job. Radio and television bulletins carried news from local protests around the country and even the BBC's Question Time kicked off with a question from a nurse about local pay. Thursday March 30 certainly belonged to the nursing organisations, and if ministers thought that pay would be buried by now, it certainly proved that it hasn't. PMID- 27680824 TI - Commons date set for debate on pay. AB - MPs will debate nurses' pay for the first time on April 20, the day thousands of nurses are expected to take part in a mass lobby of parliament. PMID- 27680825 TI - Five in six trusts fail to meet deadline for local pay deals. AB - The vast majority of nurses had heard nothing from trusts about their pay offers by April 1, the day their pay should have been increased. PMID- 27680826 TI - Thousands join in lunchtime demos as the balloon goes up. AB - Tens of thousands of nurses joined other health workers in more than 400 lunchtime protests outside hospitals last week against the government's 1 per cent pay offer. PMID- 27680827 TI - Local poll hints at refusal to work overtime. AB - Most nurses regularly do unpaid overtime and are ready to refuse to if they do not get what they see as a fair pay deal, a survey has shown. PMID- 27680828 TI - Fair pay protest. AB - Below: Nurses from London's Moorfields Eye Hospital leaflet commuters. Right: Protestors from City Hospital Trust in Birmingham. Ear right: The scene at Neath General Hospital. PMID- 27680829 TI - Midwives hit back over minister's 3 per cent claims. AB - The Royal College of Midwives has hit back at health minister Gerald Malone for accusing the union of misleading the public by suggesting nurses and midwives were being offered a 1 per cent pay rise. PMID- 27680830 TI - NHS internal market 'has led to fewer beds'. AB - The creation of the internal market in the NHS has led to fewer beds and an increase in the number of people waiting for treatment, researchers at the Labour Research Department have claimed. PMID- 27680831 TI - Staff 'coping well' after seventh arson at hospital. AB - Staff at a hospital hit by seven arson attacks in two weeks are 'coping magnificently' with the situation, a manager has said. PMID- 27680832 TI - Powerful voice. AB - Department of Health chief nursing officer Yvonne Moores has been appointed to an internal committee which makes key policy and professional decisions. The NHS Executive said her seat on the Departmental Management Board gave nursing a powerful voice. PMID- 27680833 TI - ? AB - Open wide: a new feeding room for mothers with babies in special care has been opened at Hammersmith Hospital in London, sponsored by Milupa. Pictured are, left to right: Caroline Dalmedo, nursery nurse; Joan Charlton, Milupa regional medical manager, and Kathy Sleath, clinical nurse specialist. PMID- 27680834 TI - Hard-nosed debate on RCN Congress agenda. AB - Decriminalisation of prostitution and the affect of fashion and the media on health are among the topics on the agenda of the RCN Congress 1995. PMID- 27680835 TI - Ashworth nurses 'need close supervision and support'. AB - Many nurses at Ashworth special hospital in Merseyside are either 'untrained' or 'inadequately trained' for the work they are required to do and consequently feel undervalued, isolated and threatened, says a report published last week by the NHS Health Advisory Service (HAS). PMID- 27680836 TI - New line-up at scottish board. AB - Scottish secretary Ian Lang has announced the new line-up of the Scottish National Board. PMID- 27680837 TI - ? AB - Sister Ann Granger was one of the staff from St Richard's Hospital in Sussex who took part in a recent exercise to show local school children what happens during a major disaster. PMID- 27680838 TI - Health agencies found lacking in proper policies to tackle abuse of the elderly. AB - Health agencies are lagging behind social services departments in planning how to deal with abuse of older people, a survey hits shown. PMID- 27680839 TI - PREP set to clear confusion. AB - The introduction of PREP and clinical supervision will help clear up the confusion among nurses surrounding issues of accountability and competence, England's chief nursing officer Yvonne Moores said last week. PMID- 27680840 TI - Practice nurse in GP role. AB - Practice nurses could diagnose and treat a large proportion of patients with minor illnesses who currently see their GP, recent research has shown. PMID- 27680841 TI - Students gain insight into money matters. AB - Student nurses in Chester are being offered short-term placements in purchasing as part of a new pilot programme to include areas not traditionally covered by Project 2000 courses. PMID- 27680842 TI - Protest at rent rises and mouse-traps. AB - Student nurses in Yorkshire are locked in bitter dispute over claims of poor quality accommodation and rising rents. PMID- 27680844 TI - Career fears stall staff in court claims. AB - Nurses are foiling to come forward in litigation cases because they are terrified of damaging their careers, a leading Edinburgh solicitor has warned. PMID- 27680843 TI - All nurses must learn about reality of market forces. AB - Market forces are here to stay and the sooner that nurses understand them and use them to their advantage, the better for the profession, a private sector nursing consultant claimed at the conference last week. PMID- 27680846 TI - Health problems in Glasgow under the spotlight. AB - The RCN launched its 'Nursing for Scotland' campaign last week with a leaflet mailed to every household in Glasgow. PMID- 27680845 TI - Call for proactive role in multi-skilling movement. AB - Nursing must be more proactive and less reactive in the face of the multi skilling movement, a leading international figure told the conference. PMID- 27680847 TI - Grief experience after the death of a pet. AB - The grief experienced by people at the death of a pet is similar to that associated with the death of a significant person, American researchers report. PMID- 27680849 TI - Sugar in relation to vitamin intake. AB - COMA recommendations that less than 10 per cent of dietary energy be derived from sugar might err on the side of caution in respect of any adverse effect on dietary quality, researchers say. PMID- 27680848 TI - Anti-clotting drugs best in afternoon. AB - Tissue plasminogen factor, a 'dot busting' drug given to patients after myocardial infarction, might work better when given after midday. PMID- 27680850 TI - Men conceal their fears about health. AB - Men are bottling up worries about their health instead of taking steps to improve it, a new survey has shown. PMID- 27680851 TI - 'We shall not be moved'. AB - As scores of nurses and other health workers gathered outside Great Ormond Street Hospital to campaign for a fair pay deal, the jazz band playing to entertain the crowds struck up with ?We Shall Not Be Moved?. No one sang along, but the sentiments seemed to sum up the mood of protesters. PMID- 27680852 TI - It's top of the shops. AB - Nurses in Wales have been rewarded for moving health promotion to the top of their agenda. PMID- 27680853 TI - Waste not, want not. AB - Two recent surveys suggest that the turnover of NHS nurses is on the increase and that the recent decline in wastage has ceased. An IES survey of newly qualified nurses shows that one in three changed jobs between 1992 and 1994 ( 1 ). PMID- 27680854 TI - You done right to question standards. AB - I would like to thank Christopher Goodall for pointing out an irritation the size of a carbuncle (Kan yu spel propply, Viewpoint, March 15). PMID- 27680855 TI - Hope for revolution in student welfare. AB - It is reassuring to see that colleges of nursing continue to look after the social interests of their students. The letter from Sandy Sankar, Student rent rise is not our fault (March 15), expresses an opinion not unfamiliar to many a student who ever experienced difficulties, particularly with accommodation. PMID- 27680856 TI - Ballot all RCN members now. AB - The Royal College of Midwives recently balloted its members regarding the removal of the 'no strike' policy. Following the results of the ballot, I phoned my local Royal College of Nursing office to enquire whether the RCN Council had made a decision regarding balloting of its members. I believe no decision has, as yet, been made. PMID- 27680857 TI - Every nurse should fight for fair deal. AB - It is good to see that some trusts around the country have seen sense and awarded their nurses the full 3 per cent we are campaigning for without too much hassle. PMID- 27680858 TI - Afghan charity seeks help with amputees. AB - Please may I introduce our organisation, Afghan Amputee Bicyclists for Rehabilitation, a charitable organisation in Jalalabad, working for disabled Afghan people. PMID- 27680859 TI - All staff should learn control and restraint. AB - It is welcome that the RCN has developed an outline curriculum for training control and restraint (C&R) instructors and has started validating instructor courses accordingly (Break the lock, Viewpoint, March 1). PMID- 27680860 TI - Information exchange. AB - * I am investigating the potential for a combined wound care assessment and prescription chart. I would be interested to hear from anyone who has experience of a design and/or use of a prescription chart for wound care products. Copies of such charts would be useful. PMID- 27680861 TI - ? AB - Southend Health Care NHS Trust has offered qualified nurses and mid wives a 3.5 per cent pay rise, not Southend Community Care NHS Trust as mentioned in Nursing Standardon March 22. PMID- 27680862 TI - Readers Panel. AB - Our experts consider a hot topic of the day. PMID- 27680863 TI - The trouble with transplants. AB - The transplantation of organs has become an accepted part of healthcare and yet scant attention has been given to the question of whether or not it is a good thing. PMID- 27680864 TI - Advertising HIV. AB - Think of advertising and what comes to mind, soap powders, motor cars, baked beans? All of these, of course, are heavily advertised, but what about HIV? Among the most durable of the government's advertisement campaigns have been the ones concerning HIV. Tens of millions of pounds have been spent telling the public of the presence and dangers of the virus. PMID- 27680865 TI - Listings. AB - As there is such a huge demand for the publication of free listings, readers may wish to take advantage of a new service being launched by Nursing Standard. For further details please see the coupon on page 69 or contact Veronica Brown, telephone 0181 423 1066. PMID- 27680866 TI - Unexpected Atrial Septal Intramural Hematoma During Coronary Angiography. PMID- 27680867 TI - Identifying With a Stereotype: The Divergent Effects of Exposure to Homosexual Television Characters. AB - Scholars examining homosexual television characters have typically come to one of two conclusions: either exposure to homosexual characters can lead to increased acceptance, or homosexual characters serve to reaffirm negative stereotypes. We seek to bridge these two bodies of research by introducing the concept of stereotyped identification-the idea that cognitively and emotionally identifying with fictional characters can increase acceptance of minorities, while reinforcing implicit stereotypes about how they look, act, and talk. Results from our national survey (N = 972) offer support for this hypothesis. PMID- 27680868 TI - Structural Exploration of Quinazolin-4(3H)-ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies. AB - Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo 2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED50 = 23.5 mg/kg, MES, mice, i.p.; ED50 = 32.6 mg/kg, scPTZ, mice, i.p.; ED50 = 45.2 mg/kg, 6-Hz, mice, i.p.; TD50 = 325.9 mg/kg, mice, i.p.). In addition, investigation of compound 4l in mice for its pharmacological profile proved it as safer anticonvulsant, devoid of the side effects such as motor dysfunction and hepatotoxicity of classical antiepileptic drugs (ED50 = 26.1 mg/kg, MES, mice, i.p.; ED50 = 79.4 mg/kg, scPTZ, mice, i.p.; TD50 = 361.2 mg/kg, mice, i.p.). We also predicted physiochemical and pharmacokinetic properties of structurally optimized quinazolin-4(3H)-ones by a computational protocol. A combination of in vivo anticonvulsant profile, ex vivo toxicity, and in silico studies suggested that the synthesized compounds may be useful as broad-spectrum anti-seizure drug candidates with favorable pharmacokinetic parameters. PMID- 27680869 TI - ICER is requisite for Th17 differentiation. AB - Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORgammat. In vitro differentiation from naive ICER/CREM deficient CD4+ T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4+ T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17 dependent manner. PMID- 27680870 TI - Regulation of BZR1 in fruit ripening revealed by iTRAQ proteomics analysis. AB - Fruit ripening is a complex and genetically programmed process. Brassinosteroids (BRs) play an essential role in plant growth and development, including fruit ripening. As a central component of BR signaling, the transcription factor BZR1 is involved in fruit development in tomato. However, the transcriptional network through which BZR1 regulates fruit ripening is mostly unknown. In this study, we use isobaric tags for relative and absolute quantitation (iTRAQ) labeling technology to explore important proteins regulated by BZR1 in two independent tomato transgenic lines over-expressing BZR1-1D at four ripening stages, identifying 411 differentially expressed proteins. These proteins were implicated in light reaction, plant hormone pathways and cell-wall-related metabolism, etc. The 'light reaction' metabolic pathway was identified as a markedly enhanced pathway by BZR1 during tomato fruit ripening. The protein level of a probable 2 oxoglutarate-dependent dioxygenase 2-ODD2, involved in gibberellin biosynthesis was significantly increased at all four developmental and ripening stages. The results reveal molecular links between BR signaling pathway and downstream components involved in multiple ripening-associated events during tomato fruit ripening, which will provide new insights into the molecular mechanisms underlying tomato ripening regulatory networks, and be potential in understanding BR-regulated fruit ripening. PMID- 27680871 TI - Influence of visual observational conditions on tongue motor learning. AB - The aim of this study was to investigate the impact of visual observational conditions on performance during a standardized tongue-protrusion training (TPT) task and to evaluate subject-based reports of helpfulness, disturbance, pain, and fatigue, due to the observational conditions on 0-10 numerical rating scales. Forty-eight healthy participants performed a 1-h standard TPT task. Participants were randomly assigned to one of the following three groups with different observational conditions: group 1, model observation (participants watched a prerecorded video showing standard TPT before optimal TPT being performed); group 2, self-observation (participants watched live video feedback of their own TPT performance); and group 3, control group (participants performed the TPT with no conditioning). There was no overall difference between groups but TPT performance increased over time. A significant group*time interaction indicated that the self observation group performed significantly better than the model-observation group in the last 20 min of TPT. The subject-based reports of video helpfulness showed that the model-observation group rated the prerecorded video as more helpful for TPT performance compared with the other groups but there was no significant difference between groups regarding the level of disturbance, pain, or fatigue. Self-observation of tongue-training facilitated behavioral aspects of tongue motor learning compared with model observation but not compared with control. PMID- 27680872 TI - The Dual Role of PEDF in the Pathogenesis of OHSS: Negating Both Angiogenic and Inflammatory Pathways. AB - CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is a potentially life threatening complication of assisted reproductive technologies. This complex syndrome is known to involve massive angiogenesis and inflammation. We have previously established the anti-angiogenic involvement of pigment epithelium derived factor (PEDF) in the pathophysiology and treatment of OHSS. OBJECTIVE: Evaluate the anti-inflammatory role of PEDF in OHSS. DESIGN: In vivo mouse OHSS model and in vitro cultures of granulosa cells. MAIN OUTCOME: Changes in the expression of PEDF, IL-6, IL-8, and vascular endothelial growth factor (VEGF) were measured by quantitative PCR and ELISA; OHSS symptoms were recorded (body and ovarian weight gain and peritoneal vascular leakage quantified by the modified Miles's assay). RESULTS: Rat granulosa cell-line stimulated with lysophosphatidic acid (LPA), exhibited a significant increase in IL-6 expression, concomitantly with a decrease in PEDF level (P < .01). Co-stimulation with recombinant PEDF (rPEDF) decreased the expression of IL-6 significantly (P < .05). Furthermore, the expression of IL-6 and IL-8 increased in LPA-stimulated human primary granulosa cells (P < .01). Co-stimulation with rPEDF decreased the expression of LPA-induced IL-6 and IL-8 mRNA and protein by 4- and 2- to 5-fold, respectively. IL-8-stimulated human primary granulosa cells exhibited increased expression of VEGF mRNA; co-stimulation with hCG induced a significantly higher increase in the expression of VEGF mRNA (P < .001), which was counteracted by rPEDF. Subcutaneous injection of 0.5 mg/kg rPEDF to OHSS-induced mice reduced the increased expression of IL-6 in the ovary (P < .01) and alleviated the severity of all OHSS parameters. CONCLUSIONS: Our findings provide a framework that correlates down-regulation of OHSS symptoms caused by PEDF with both angiogenic and inflammatory pathways. PMID- 27680873 TI - A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia. AB - CONTEXT: Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. OBJECTIVE: This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. DESIGN: Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. MAIN OUTCOME MEASURES: The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17 OHP) <=1200 ng/dL was measured. RESULTS: CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700 hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. CONCLUSIONS: CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study. PMID- 27680874 TI - The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma. AB - CONTEXT: The microphthalmia-associated transcription factor (MITF) regulates the survival, proliferation, and differentiation of neural crest-derived lineages. Recent studies reported an increased risk of melanoma in individuals carrying the rare variant MITF, p.E318K (rs149617956). Whether this variant plays a role in other neural crest-derived tumors is unknown. OBJECTIVE: In the present study, we aimed at determining the prevalence of the MITF, p.E318K variant, in a well characterized French cohort of pheochromocytomas/paragangliomas (PCC/PGL). DESIGN AND METHODS: Genomic DNA from 555 unrelated patients with PCC/PGL was genotyped for the p.E318K variant in MITF using Sanger sequencing. MAIN OUTCOME MEASURE: The prevalence of the mutation in the PCC/PGL cohort was compared with a population-based sample of 2348 ethnically matched controls. RESULTS: We identified seven carriers (five patients with sporadic PCCs, two with PGLs). The prevalence of the MITF, p.E318K variant, was higher in the PCC/PGL cohort than in controls, and appears to be a significant risk factor (odds ratio, 3.19; 95% confidence interval, 1.34-7.59; P = .005). Noteworthy, two patients were homozygous for the p.E318K risk allele, a patient with metastatic PCC and an SDHB mutated patient with PGL. CONCLUSION: Our results indicate that the germline variant MITF, p.E318K is associated with an increased risk of other neural crest derived tumors such as PCC/PGL. PMID- 27680875 TI - Independent Contributions of Nocturnal Hot Flashes and Sleep Disturbance to Depression in Estrogen-Deprived Women. AB - CONTEXT: Women are at increased risk for mood disturbance during the menopause transition. Hot flashes (HFs), sleep disruption, and fluctuating estradiol levels correlate with menopause-associated depression but co-occur, making cause and effect relationships difficult to disentangle. OBJECTIVE: Using a GnRH agonist (GnRHa) experimental model, we investigated whether depressive symptoms are associated with HFs and/or are explained by concomitant sleep fragmentation in the absence of estradiol fluctuation. DESIGN AND INTERVENTION: Depressive symptoms, objective polysomnographic sleep parameters, subjective sleep quality, serum estradiol, and HFs were assessed before and 4 weeks after open-label depot GnRHa (leuprolide 3.75-mg) administration. SETTING: Academic medical center. PARTICIPANTS: Twenty-nine healthy nondepressed premenopausal volunteers (mean age, 27.3 years). RESULTS: Serum estradiol was rapidly and uniformly suppressed. HFs developed in 69% of the subjects. On univariate analysis, worsening of mood was predicted by increases in time in light sleep (stage N1), number of transitions to wake, non-REM arousals, subjective sleep quality, and reductions in perceived sleep efficiency (all P < .045), as well as the number of nighttime (P = .006), but not daytime (P = .28), HFs reported. In adjusted models, the number of nighttime HFs reported, increases in non-REM arousals, time in stage N1, transitions to wake, and reduced sleep quality remained significant predictors of mood deterioration (P <= .05). CONCLUSIONS: Depressive symptoms emerged after estradiol withdrawal in association with objectively and subjectively measured sleep disturbance and the number of nighttime, but not daytime, HFs reported. Results suggest that sleep disruption and perceived nighttime HFs both contribute to vulnerability to menopause-associated depressive symptoms in hypoestrogenic women. PMID- 27680876 TI - A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison's Disease in Humans. AB - CONTEXT: Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. OBJECTIVE: We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. DESIGN, SETTING, AND PATIENTS: This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs3757247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls. RESULTS: The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 * 10-4; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.29-2.18; WTCCC2 controls, P = 1.4 * 10-6; OR, 1.44; 95% CI, 1.23-1.69). This finding was replicated in the Norwegian validation cohort (P = .0015; OR, 1.41; 95% CI, 1.14-1.75). Subgroup analysis showed that this association is present in subjects with both isolated AAD (OR, 1.53; 95% CI, 1.22-1.92) and autoimmune polyglandular syndrome type 2 (OR, 1.37; 95% CI, 1.12-1.69) in the UK cohort, and with autoimmune polyglandular syndrome type 2 in the Norwegian cohort (OR, 1.58; 95% CI, 1.22-2.06). CONCLUSION: We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a "universal" autoimmune susceptibility locus. PMID- 27680879 TI - Comparing Children's and Caseworkers' Reports of Physical Violence. AB - In cases of suspected child maltreatment, the caseworkers' evaluations of the harm and risk to the child are vital in determining if children are being abused and ultimately whether services are provided to the family. These evaluations are dependent on information caseworkers are able to uncover during their investigation, but may not reflect the experiences of the child. Using data from the National Survey of Child and Adolescent Well-Being (NSCAW-I), this study first compares how consistent children's claims of physical victimization are with caseworkers' assessments of harm, severity of risk, and whether there is physical abuse occurring. Second, we examine whether any discrepancies are influenced by the demographic characteristics of the child. Based on cross tabulations, mean tests of difference, and one-way ANOVA, we find a high degree of overlap in children's reports of violence with caseworkers' reports of harm, the potential for risk, and the presence of physical abuse. However, there are also important differences. Among children who reported acts of physical violence occurred "lots of times," 23% of the cases were viewed by the caseworker as causing "no harm" to the child and over 60% were not regarded as physical abuse. The children's age and sex are both significant predictors of discrepancies, with more discrepancies between caseworkers and young children or teens as well as boys. Implications of this study are that additional training is needed to help caseworkers build rapport with the children. We also suggest that Child Protective Services (CPS) should implement alternative ways for children to report their experiences other than face-to-face interviews with caseworkers. PMID- 27680877 TI - Nuchal Skinfold Thickness: A Novel Parameter for Assessment of Body Composition in Childhood Craniopharyngioma. AB - CONTEXT: Hypothalamic obesity, cardiovascular disease (CVD), and relapse/progression have a major impact on prognosis in childhood-onset craniopharyngioma (CP). We analyzed nuchal skinfold thickness (NST) on magnetic resonance imaging performed for follow-up monitoring as a novel parameter for body composition (BC) and CVD in CP. OBJECTIVE: The objective of the study was to identify the association of NST with body mass index (BMI), waist to height ratio (WHtR), functional capacity, and blood pressure (BP) in CP and controls. DESIGN: This was a cross-sectional and longitudinal prospective study in CP patients. SETTING: The study was conducted at HIT-Endo, KRANIOPHARYNGEOM 2000/2007. PATIENTS: Participants included 94 CP patients and 75 controls. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Association of NST with BC and BP in 43 CP and 43 controls was measured. RESULTS: NST correlated with BMI SD score (SDS; r = 0.78; P < .001; n = 169) and WHtR (r = 0.85; P < .001; n = 86) in the total cohort and CP patients (NST-BMI SDS: r = 0.77, P < .001, n = 94); NST WHtR: r = 0.835, P < .001, n=43) and controls (NST-BMI SDS: r = 0.792, P < .001, n = 75; NST-WHtR: r = 0.671, P < .001, n = 43). In CP, systolic BP correlated with NST (r = 0.575, P < .001), BMI SDS (r = 0.434, P = .004), and WHtR (r = 0.386, P = .011). Similar results were observed for diastolic BP in CP. In multivariate analyses, NST had a predictive value for hypertension in postpubertal CP and controls (odds ratio 6.98, 95% confidence interval [1.65, 29.5], P = .008). During a longitudinal follow-up, changes in NST correlated with changes in BMI SDS (P < .001) and WHtR (P = .01) but not with changes in BP and functional capacity. CONCLUSIONS: Because monitoring of magnetic resonance imaging and BC is essential for follow-up in CP, NST could serve as a novel and clinically relevant parameter for longitudinal assessment of BC and CVD risk in CP. PMID- 27680878 TI - Temporal dynamics of hot desert microbial communities reveal structural and functional responses to water input. AB - The temporal dynamics of desert soil microbial communities are poorly understood. Given the implications for ecosystem functioning under a global change scenario, a better understanding of desert microbial community stability is crucial. Here, we sampled soils in the central Namib Desert on sixteen different occasions over a one-year period. Using Illumina-based amplicon sequencing of the 16S rRNA gene, we found that alpha-diversity (richness) was more variable at a given sampling date (spatial variability) than over the course of one year (temporal variability). Community composition remained essentially unchanged across the first 10 months, indicating that spatial sampling might be more important than temporal sampling when assessing beta-diversity patterns in desert soils. However, a major shift in microbial community composition was found following a single precipitation event. This shift in composition was associated with a rapid increase in CO2 respiration and productivity, supporting the view that desert soil microbial communities respond rapidly to re-wetting and that this response may be the result of both taxon-specific selection and changes in the availability or accessibility of organic substrates. Recovery to quasi pre disturbance community composition was achieved within one month after rainfall. PMID- 27680881 TI - Influence of sibutramine in addition to diet and exercise on the relationship between weight loss and blood glucose changes. AB - Aims: Weight loss is expected to improve glycaemic control in patients with diabetes or at high risk hereof. Sibutramine causes weight loss and is associated with an increased risk of myocardial infarction and stroke in high-risk patients. We examined the impact of sibutramine-induced weight loss on glycaemic control. Methods and results: In total, 8192 obese patients with diabetes were randomized to sibutramine or placebo plus diet and exercise after a preliminary 6 weeks in which all patients received sibutramine. Patients were classified into four groups of weight change. A total of 1582 patients had a weight loss >5.7 kg; 2047 patients lost 3.7-5.7 kg; 2432 patients lost <3.7 kg, and 1875 patients gained weight. Patients on sibutramine lost slightly more weight than those on placebo ( 0.2 kg on average, P < 0.0001). Mean blood glucose changes in the placebo group were -0.6 mmol/L (+/-3.1, P = 0.0002), -0.2 mmol/L (+/-2.7, P = 0.04), and -0.1 mmol/L (+/-3.0, P = 0.01) in the moderate, modest, and mild weight loss groups, respectively; in the weight gain group blood glucose levels increased by +0.2 mmol/L (+/-3.1, P = 0.003). Corresponding mean blood glucose changes in the sibutramine-treated patients were -0.4 mmol/L (+/-3.2, P = 0.0002), +0.1 mmol/L (+/-3.0, P = 0.04), +0.4 mmol/L (+/-2.8, P = 0.01), and +0.2 mmol/L (+/-3.4, P = 0.003). Mean values of HbA1c followed the same pattern though the HbA1c changes were smaller with weight loss and greater with weight gain in the sibutramine group. All results were statistically significant (P < 0.0001). Conclusion: Weight loss induced by sibutramine, diet, and exercise attenuates falls in blood glucose levels and HbA1c compared with similar weight loss with placebo, diet, and exercise. PMID- 27680880 TI - A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants. AB - AIMS: We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin. METHODS: Using nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding. RESULTS: In total 32 675 AF patients were identified (58% men, median age 74 years): 11 427 patients used warfarin, 7925 dabigatran, 6817 rivaroxaban, and 6506 apixaban. After a median follow-up of 173 days (25th, 75th percentile 84, 340), 2081 (6.37%) patients experienced a first major or CRNM bleeding. Using a Cox proportional hazard model adjusting for baseline characteristics, use of apixaban [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.61-0.80, P < 0.001] and dabigatran (HR 0.74, 95% CI 0.66-0.84, P < 0.001) were associated with a lower risk of major or CRNM bleeding compared with warfarin whereas use of rivaroxaban was not (HR: 1.05, 95% CI 0.94-1.17, P = 0.400). Use of dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding, whereas use of apixaban and dabigatran were associated with lower risk of intracranial bleeding, compared with warfarin. CONCLUSION: In this nationwide cohort study in AF patients, apixaban and dabigatran were associated with a lower risk of major or CRNM bleeding compared with warfarin. The risk of gastrointestinal bleeding was higher with rivaroxaban and dabigatran compared with warfarin. PMID- 27680882 TI - Ultrasound Pretreatment as an Useful Tool to Enhance Egg White Protein Hydrolysis: Kinetics, Reaction Model, and Thermodinamics. AB - The impact of ultrasound waves generated by probe-type sonicator and ultrasound cleaning bath on egg white protein susceptibility to hydrolysis by alcalase compared to both thermal pretreatment and conventional enzymatic hydrolysis was quantitatively investigated. A series of hydrolytic reactions was carried out in a stirred tank reactor at different substrate concentrations, enzyme concentrations, and temperatures using untreated, and pretreated egg white proteins (EWPs). The kinetic model based on substrate inhibition and second-order enzyme deactivation successfully predicts the experimental behavior providing an effective tool for comparison and optimization. The ultrasound pretreatments appear to greatly improve the enzymatic hydrolysis of EWPs under different conditions when compare to other methods. The apparent reaction rate constants for proteolysis (k2 ) are 0.009, 0.011, 0.053, and 0.045 min-1 for untreated EWPs, and those pretreated with heat, probe-type sonicator, and ultrasound cleaning bath technologies, respectively. The ultrasound pretreatment also decreases hydrolysis activation (Ea ) and enzyme deactivation (Ed ) energy, enthalpy (DeltaH), and entropy (DeltaS) of activation and for the probe-type sonication this decrease is 61.7%, 61.6%, 63.6%, and 32.2%, respectively, but ultrasound has little change in Gibbs free energy value in the temperature range of 318 to 338 K. The content of sulfhydryl groups and zeta potential show a significant increase (P < 0.05) for both applied ultrasound pretreatments and the reduction of particle size distribution are achieved, providing some evidence that the ultrasound causes EWP structural changes affecting the proteolysis rate. PMID- 27680883 TI - A Macroscopic Mathematical Model for Cell Migration Assays Using a Real-Time Cell Analysis. AB - Experiments of cell migration and chemotaxis assays have been classically performed in the so-called Boyden Chambers. A recent technology, xCELLigence Real Time Cell Analysis, is now allowing to monitor the cell migration in real time. This technology measures impedance changes caused by the gradual increase of electrode surface occupation by cells during the course of time and provide a Cell Index which is proportional to cellular morphology, spreading, ruffling and adhesion quality as well as cell number. In this paper we propose a macroscopic mathematical model, based on advection-reaction-diffusion partial differential equations, describing the cell migration assay using the real-time technology. We carried out numerical simulations to compare simulated model dynamics with data of observed biological experiments on three different cell lines and in two experimental settings: absence of chemotactic signals (basal migration) and presence of a chemoattractant. Overall we conclude that our minimal mathematical model is able to describe the phenomenon in the real time scale and numerical results show a good agreement with the experimental evidences. PMID- 27680885 TI - Rapid Increase in Serum Low-Density Lipoprotein Cholesterol Concentration during Hepatitis C Interferon-Free Treatment. AB - BACKGROUND & AIM: We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients' serum low-density lipoprotein cholesterol (LDL-C) concentration. METHODS: We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks. DeltaLDL-C was defined as the changed in LDL-C level at 28 days from the start of therapy. To determine whether DeltaLDL-C was associated with several kinds of factors including viral kinetics, we performed a stepwise multiple linear regression analysis. RESULTS: The LDL-C levels in patients treated with LDV/SOF were markedly and significantly elevated (87.45 to 122.5 mg/dl; p<10-10) compared to those in the DCV/ASV-treated patients (80.15 to 87.8 mg/dl; p = 0.0056). The median levels of DeltaLDL-C in the LDV/SOF and DCV/ASV groups were 33.2 and 13.1, respectively. LDV/SOF combination therapy as an IFN-free regimen (p<0.001) and DeltaHCV core antigen (0-1 day drop) (p<0.044) were identified as independent factors that were closely related to the DeltaLDL-C. CONCLUSIONS: A rapid increase in the serum LDL-C concentration during the IFN-free treatment of hepatitis C was associated with the type of HCV therapy and a decline of HCV core protein. PMID- 27680886 TI - Static micro-array isolation, dynamic time series classification, capture and enumeration of spiked breast cancer cells in blood: the nanotube-CTC chip. AB - We demonstrate the rapid and label-free capture of breast cancer cells spiked in blood using nanotube-antibody micro-arrays. 76-element single wall carbon nanotube arrays were manufactured using photo-lithography, metal deposition, and etching techniques. Anti-epithelial cell adhesion molecule (anti-EpCAM), Anti human epithelial growth factor receptor 2 (anti-Her2) and non-specific IgG antibodies were functionalized to the surface of the nanotube devices using 1 pyrene-butanoic acid succinimidyl ester. Following device functionalization, blood spiked with SKBR3, MCF7 and MCF10A cells (100/1000 cells per 5 MUl per device, 170 elements totaling 0.85 ml of whole blood) were adsorbed on to the nanotube device arrays. Electrical signatures were recorded from each device to screen the samples for differences in interaction (specific or non-specific) between samples and devices. A zone classification scheme enabled the classification of all 170 elements in a single map. A kernel-based statistical classifier for the 'liquid biopsy' was developed to create a predictive model based on dynamic time warping series to classify device electrical signals that corresponded to plain blood (control) or SKBR3 spiked blood (case) on anti-Her2 functionalized devices with ~90% sensitivity, and 90% specificity in capture of 1000 SKBR3 breast cancer cells in blood using anti-Her2 functionalized devices. Screened devices that gave positive electrical signatures were confirmed using optical/confocal microscopy to hold spiked cancer cells. Confocal microscopic analysis of devices that were classified to hold spiked blood based on their electrical signatures confirmed the presence of cancer cells through staining for DAPI (nuclei), cytokeratin (cancer cells) and CD45 (hematologic cells) with single cell sensitivity. We report 55%-100% cancer cell capture yield depending on the active device area for blood adsorption with mean of 62% (~12 500 captured off 20 000 spiked cells in 0.1 ml blood) in this first nanotube-CTC chip study. PMID- 27680884 TI - Differential Effects of p38, MAPK, PI3K or Rho Kinase Inhibitors on Bacterial Phagocytosis and Efferocytosis by Macrophages in COPD. AB - Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD. Concerns exist, however, about off-target effects. We investigated the effect of p38 MAPK inhibitors (VX745 and SCIO469), specific inhibitors of PI3K alpha (NVS P13K-2), delta (NVS-P13K-3) or gamma (NVS-P13K-5) and a ROCK inhibitor PF4950834 on macrophage phagocytosis, early intracellular killing of bacteria and efferocytosis of apoptotic neutrophils. Alveolar macrophages (AM) obtained from broncho-alveolar lavage (BAL) or monocyte-derived macrophages (MDM) from COPD patients (GOLD stage II/III) enrolled from a well characterized clinical cohort (MRC COPD-MAP consortium) or from healthy ex-smoker controls were studied. Both COPD AM and MDM exhibited lower levels of bacterial phagocytosis (using Streptococcus pneumoniae and non-typeable Haemophilus influenzae) and efferocytosis than healthy controls. None of the inhibitors altered bacterial internalization or early intracellular bacterial killing in AM or MDM. Conversely PF4950834, but not other inhibitors, enhanced efferocytosis in COPD AM and MDM. These results suggest none of these inhibitors are likely to exacerbate phagocytosis-related defects in COPD, while confirming ROCK inhibitors can enhance efferocytosis in COPD. PMID- 27680887 TI - Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease. AB - Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co-existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom. PMID- 27680889 TI - Efficacy of beta-Tricalcium Phosphate Graft into the Bone Defects after Bone Patellar Tendon-Bone Anterior Cruciate Ligament Reconstruction. AB - This prospective pilot study investigated whether grafting beta-tricalcium phosphate (B-TCP) into the bone-patellar tendon-bone (BPTB)-harvesting site after anterior cruciate ligament reconstruction would accelerate bone and tendon regeneration in the grafted site. Overall, 19 patients agreed prospectively to undergo regular morphological and histological examinations of the B-TCP-grafted site. Postoperative radiographic, ultrasonographic, and magnetic resonance imaging (MRI) examinations were performed to evaluate the grafted site at 1, 3, 6, and 12 months. Postoperative knee function and donor-site morbidity were assessed at 12 months using the kneeling test. A histological examination was also performed at this time Radiographic examination and MRI showed that the grafted B-TCP was completely absorbed and remodeled into normal bone structure in the tibia and patella at 6 months postoperatively. Histological and ultrasonographic examinations of all subjects showed that the grafted B-TCP was substituted by normal bone tissue, and the patellar tendon - bone junction had regenerated at 12 months postoperatively. Clinical functional knee tests showed good recovery of the donor site. All patients could perform kneeling and knee walking on hard ground. The results of this pilot study suggest that grafting B TCP into the BPTB-harvesting site promotes the remodeling process of the bone and patellar tendon structures. This surgical treatment would decrease an incidence of the anterior knee pain after ACLR using a BPTB autograft. PMID- 27680890 TI - The Varus-Valgus Constrained Knee Implant: Survivorship and Outcomes. AB - The purpose of this study was to estimate the survivorship of the varus-valgus constrained (VVC) knee implants in primary, aseptic, and septic revision total knee arthroplasty (TKA); determine functional outcomes; main modes of failure; and variables associated with increased mechanical failures. In this study, 685 consecutive cases of primary (n = 247), aseptic (n = 315), and septic revision (n = 123) TKAs with VVC implants were performed between 1999 and 2008; 533 knees (78%) had a mean follow-up of 8.2 years (range, 2-15.1). Kaplan-Meier method was used to evaluate implant survival with mechanical failure as the end point. Clinical outcomes were measured with a modified Knee Society Score (mKSS) and modified Knee Function Score (mKFS) and modes of failure were determined. Cox proportional hazards models were performed to assess for factors associated with implant failure. Ten-year survival was 88.5% (95% confidence interval [CI]: 83.9 93.5%) for primary TKAs, 75.8% (95% CI: 70.4-81.7%) for aseptic, and 54.6% (95% CI: 43.7-68.2%) for septic revisions. Improvement in pre- to postoperative mKSS and mKFS were significant in all three groups (p < 0.05). The most common mode of failure overall was infection. Mechanical modes of failures included periprosthetic fracture (45%) for primary TKA and soft tissue instability (19%) for aseptic revisions. A longer period since the last surgery in affected knee was associated with lower mechanical failures (hazards ratio of 0.55 [95% CI: 0.31-0.95], p = 0.03). VVC implant showed reliable survivorship at 10 years although careful patient selection is warranted due to the risk of infection. The main mechanical modes of failure were instability and periprosthetic fracture. PMID- 27680888 TI - Tibiofemoral Osteoarthritis and Varus-Valgus Laxity. AB - The purpose of this study was to systematically review and synthesize the literature measuring varus-valgus laxity in individuals with tibiofemoral osteoarthritis (OA). Specifically, we aimed to identify varus-valgus laxity differences between persons with OA and controls, by radiographic disease severity, by frontal plane knee alignment, and by sex. We also aimed to identify if there was a relationship between varus-valgus laxity and clinical performance and self-reported function. We systematically searched for peer-reviewed original research articles in PubMed, Scopus, and CINAHL to identify all existing literature regarding knee OA and objective measurement of varus-valgus laxity in vivo. Forty articles were identified that met the inclusion criteria and data were extracted. Varus-valgus laxity was significantly greater in individuals with OA compared with controls in a majority of studies, while no study found laxity to be significantly greater in controls. Varus-valgus laxity of the knee was reported in persons with OA and varying degrees of frontal plane alignment, disease severity, clinical performance, and self-reported function but no consensus finding could be identified. Females with knee OA appear to have more varus-valgus laxity than males. Meta-analysis was not possible due to the heterogeneity of the subject populations and differences in laxity measurement devices, applied loading, and laxity definitions. Increased varus-valgus laxity is a characteristic of knee joints with OA. Large variances exist in reported varus-valgus laxity and may be due to differences in measurement devices. Prospective studies on joint laxity are needed to identify if increased varus valgus laxity is a causative factor in OA incidence and progression. PMID- 27680892 TI - Crocin protects human erythrocytes from nitrite-induced methemoglobin formation and oxidative damage. AB - Sodium nitrite (NaNO2 ) is a common contaminant of drinking water and food and feed chain. Nitrite induces oxidative damage in humans and animals. In this work, we studied the protective effect of crocin, the active constituent of Crocus sativus (saffron), on NaNO2 -induced oxidative damage in human erythrocytes. Changes in oxidative stress parameters following NaNO2 incubation of erythrocytes in presence and absence of crocin were determined. It was found that crocin pre treatment significantly attenuated NaNO2 -induced oxidative damage of proteins, lipids, and plasma membrane. Crocin reduced the level of methemoglobin, the primary acute effect of nitrite intoxication. It also improved the antioxidant capacity of cells and NaNO2 -induced morphological changes in erythrocytes. Crocin is thus a potent protective agent against nitrite-induced cytotoxicity. PMID- 27680894 TI - Comparison of an anal fistula plug and mucosa advancement flap for complex anal fistulas: a meta-analysis. AB - OBJECTIVE: The aim of this analysis was to compare the advantages of the anal fistula plug (AFP) with the mucosa advancement flap (MAF) for complex anal fistulas. METHODS: Comparative studies of the efficacy of AFP and MAF were included. Two independent reviewers selected articles for inclusion. After information collection, a meta-analysis was performed using data on overall healing rates, complications, incontinences and recurrences. The quality of postoperative life and cost were also included with the clinical results. RESULTS: Ten studies included 778 patients who were divided into AFP and MAF groups in this meta-analysis. During the follow-up period, no significant difference in healing rates, complications and recurrences were found (P = 0.55, P = 0.78 and P = 0.23, respectively). The incontinence rate of AFP was lower than that of MAF (P = 0.04). The postoperative quality of life of AFP patients was superior to that of MAF patients. The AFP patients had less persistent pain of a shorter duration and shortened healing time and hospital stay. The treatment cost of AFP patient was lower than that of MAF. CONCLUSION: Compared to the MAF procedure, the AFP procedure has some advantages for complex anal fistulas, but more and large randomized clinical trials comparing the two procedures for fistula management need to be conducted. PMID- 27680893 TI - Utilization of surgical treatment for local and locoregional esophageal cancer: Analysis of the National Cancer Data Base. AB - BACKGROUND: Previous studies have suggested that esophagectomy is severely underused for patients with resectable esophageal cancer. The recent expansion of endoscopic local therapies, advances in surgical techniques, and improved postoperative outcomes have changed the therapeutic landscape. The impact of these developments and evolving treatment guidelines on national practice patterns is unknown. METHODS: Patients diagnosed with clinical stage 0 to III esophageal cancer were identified from the National Cancer Database (2004-2013). The receipt of potentially curative surgical treatment over time was analyzed, and multivariate logistic regression was used to identify factors associated with surgical treatment. RESULTS: The analysis included 52,122 patients. From 2004 to 2013, the overall rate of potentially curative surgical treatment increased from 36.4% to 47.4% (P < .001). For stage 0 disease, the receipt of esophagectomy decreased from 23.8% to 17.9% (P < .001), whereas the use of local therapies increased from 34.3% to 58.8% (P < .001). The use of surgical treatment increased from 43.4% to 61.8% (P < .001), from 36.1% to 45.0% (P < .001), and from 30.8% to 38.6% (P < .001) for patients with stage I, II, and III disease, respectively. In the multivariate analysis, divergent practice patterns and adherence to national guidelines were noted between academic and community facilities. CONCLUSIONS: The use of potentially curative surgical treatment has increased for patients with stage 0 to III esophageal cancer. The expansion of local therapies has driven increased rates of surgical treatment for early-stage disease. Although the increased use of esophagectomy for more advanced disease is encouraging, significant variation persists at the patient and facility levels. Cancer 2017;123:410-419. (c) 2016 American Cancer Society. PMID- 27680891 TI - Macrophages of genetically characterized familial hypercholesterolaemia patients show up-regulation of LDL-receptor-related proteins. AB - Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL. PBLs in young heterozygous genetically characterized FH patients have higher expression of LRP5 and LRP6 than age-matched healthy controls or patients with secondary hypercholesterolaemia. LRP1 levels were similar among groups. In monocyte-derived macrophages (MACs), LRP5 and LRP1 transcript levels did not differ between FHs and controls in resting conditions, but when exposed to agLDL, FH-MAC showed a highly significant up-regulation of LRP5, while LRP1 was unaffected. PBL and MAC cells from FH patients had significantly lower LDLR expression than control cells, independently of the lipid-lowering therapy. Furthermore, exposure of FH MAC to agLDL resulted in a reduced expression of CD163, scavenger receptor with anti-inflammatory and atheroprotective properties. In summary, our results show for first time that LRPs, active lipid-internalizing receptors, are up-regulated in innate immunity cells of young FH patients that have functional LDLR mutations. Additionally, their reduced CD163 expression indicates less atheroprotection. Both mechanisms may play a synergic effect on the onset of premature atherosclerosis in FH patients. PMID- 27680895 TI - Emergency nurses' evaluation of observational pain assessment tools for older people with cognitive impairment. AB - AIMS AND OBJECTIVES: To explore emergency nurses' perceptions of the feasibility and utility of Pain Assessment in Advanced Dementia tool in people over 65 with cognitive impairment. The Pain Assessment in Advanced Dementia tool was then compared with The Abbey Pain Scale, Doloplus-2 and PACSLAC. The objective was to determine which observational pain assessment tool was the most appropriate for the emergency department context and the cognitively impaired older person. BACKGROUND: The number of older people with cognitive impairment conditions, such as dementia, presenting to the emergency department is increasing. Approximately 28% of people over 65 years who present will have cognitive impairment. Older people with cognitive impairment often receive suboptimal pain management in the ED. There is limited evidence of the use and/or appropriateness of dementia specific pain observation assessment tools in the ED. DESIGN: This was a multicentre exploratory qualitative study, which was conducted within a constructivist paradigm. METHODS: Focus group interviews were conducted with nurses across three hospital emergency departments. Data were subject to thematic analysis. RESULTS: Six focus groups were conducted with 36 nurses over a 12-week period. Four themes emerged from the analysis: 1) cognitive impairment is a barrier to pain management; 2) PAINAD gives structure to pain assessment; 3) PAINAD assists to convey pain intensity; and 4) selection of an appropriate observational pain assessment tool. CONCLUSIONS: This study identified that emergency nurses find it challenging to detect, assess and manage pain in cognitively impaired people. While the use of the PAINAD helped to address these challenges compared to other tools, nurses also identified the important role that family and carers can play in pain assessment and management for older people with cognitive impairment. RELEVANCE TO CLINICAL PRACTICE: This study has generated new knowledge that has broad application across clinical settings, which can assist to transform pain management practice and reduce human suffering. The use of an observational pain assessment tool can provide for greater practice consistency for patients with communication difficulties. Pain management for older people with cognitive impairment is best achieved by the use an appropriate observational pain assessment tool and with a multidisciplinary approach that includes the person and their family/carer. PMID- 27680897 TI - Interviews with paediatric rheumatologists about psoriasis and psoriatic arthritis in children: how can specialties learn from each other? PMID- 27680896 TI - Choosing appropriate analysis methods for cluster randomised cross-over trials with a binary outcome. AB - In cluster randomised cross-over (CRXO) trials, clusters receive multiple treatments in a randomised sequence over time. In such trials, there is usual correlation between patients in the same cluster. In addition, within a cluster, patients in the same period may be more similar to each other than to patients in other periods. We demonstrate that it is necessary to account for these correlations in the analysis to obtain correct Type I error rates. We then use simulation to compare different methods of analysing a binary outcome from a two period CRXO design. Our simulations demonstrated that hierarchical models without random effects for period-within-cluster, which do not account for any extra within-period correlation, performed poorly with greatly inflated Type I errors in many scenarios. In scenarios where extra within-period correlation was present, a hierarchical model with random effects for cluster and period-within cluster only had correct Type I errors when there were large numbers of clusters; with small numbers of clusters, the error rate was inflated. We also found that generalised estimating equations did not give correct error rates in any scenarios considered. An unweighted cluster-level summary regression performed best overall, maintaining an error rate close to 5% for all scenarios, although it lost power when extra within-period correlation was present, especially for small numbers of clusters. Results from our simulation study show that it is important to model both levels of clustering in CRXO trials, and that any extra within-period correlation should be accounted for. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27680899 TI - Young researchers thrive in life after academia. PMID- 27680898 TI - Educational differences in responses to breast cancer symptoms: A qualitative comparative study. AB - OBJECTIVE: Advanced stage at diagnosis for breast cancer is associated with lower socio-economic status (SES). We explored what factors in the patient interval (time from noticing a bodily change to first consultation with a health care professional) may contribute to this inequality. DESIGN: Qualitative comparative study. METHODS: Semi-structured interviews with a sample of women (>=47 years) from higher (n = 15) and lower (n = 15) educational backgrounds, who had experienced at least one potential breast cancer symptom. Half the participants (n = 15) had sought medical help, half had not (n = 15). Without making breast cancer explicit, we elicited women's sense-making around their symptoms and help seeking decisions. RESULTS: Containment of symptoms and confidence in acting upon symptoms emerged as two broad themes that differentiated lower and higher educational groups. Women from lower educational backgrounds tended to attribute their breast symptoms to trivial factors and were reticent in using the word 'cancer'. Despite 'knowing' that symptoms could be related to cancer, women with lower education invoked lack of medical knowledge - 'I am not a doctor' - to express uncertainty about interpreting symptoms and accessing help. Women with higher education were confident about interpreting symptoms, seeking information online, and seeking medical help. CONCLUSIONS: Our findings suggest that knowledge of breast cancer alone may not explain socio-economic differences in how women respond to breast cancer symptoms as women with lower education had 'reasons' not to react. Research is needed on how to overcome a wider spectrum of psycho-social factors to reduce future inequality. Statement of contribution What is already known on this subject? Seven of ten breast cancers in the UK are diagnosed after people contact their doctor with symptoms. Women from lower socio economic backgrounds are more likely to be diagnosed with advanced disease. There is little evidence related to potential drivers of this SES inequality. What does this study add? We qualitatively explored socio-economic (SES) differences in help-seeking for breast symptoms. Women with higher education were more confident about interpreting symptoms and navigating health care. Women with lower education were more reluctant to seek help due to fear of cancer. PMID- 27680900 TI - The maximum climate ambition needs a firm research backing. PMID- 27680901 TI - The challenges facing Habitat III. PMID- 27680902 TI - Encourage governments to heed scientific advice. PMID- 27680903 TI - Biotechnology: Portable way to make proteins. PMID- 27680905 TI - Epigenetics: CRISPR edits gene methylation. PMID- 27680904 TI - Glaciology: Greenland ice loss underestimated. PMID- 27680906 TI - Stem cells: Targeting pain of spinal-cord injury. PMID- 27680907 TI - Materials: Graphene jiggles up and down. PMID- 27680909 TI - Agriculture: Maize engineered to kill pest. PMID- 27680908 TI - Neuroscience: Ants get addicted to morphine. PMID- 27680910 TI - Computer science: Ancient scroll virtually unrolled. PMID- 27680911 TI - Astronomy: Early star-forming gas found. PMID- 27680912 TI - Ecology: Rats and cats drive extinctions. PMID- 27680913 TI - African elephants, forensic science and China's gene bank. PMID- 27680914 TI - Daring Chinese telescope is poised to transform astronomy. PMID- 27680915 TI - Facebook couple commits $3 billion to cure disease. PMID- 27680916 TI - Cuban crocodiles pose conservation conundrum. PMID- 27680917 TI - Worldwide brain-mapping project sparks excitement - and concern. PMID- 27680918 TI - Solar on the steppe: Ukraine embraces renewables revolution. PMID- 27680919 TI - Zimbabwean scientists fight to preserve national academy. PMID- 27680920 TI - Correction. PMID- 27680921 TI - Can Cuban science go global? PMID- 27680922 TI - Boost resilience of small and mid-sized cities. PMID- 27680923 TI - Where to put the next billion people. PMID- 27680924 TI - Give cities a seat at the top table. PMID- 27680928 TI - Species loss: a crude view of climate. PMID- 27680929 TI - Food systems: Nourish as well as feed the world. PMID- 27680930 TI - Species loss: diverse takes on biodiversity. PMID- 27680931 TI - Meteorology: Mobile networks aid weather monitoring. PMID- 27680932 TI - Species loss: climate plan saves only trees. PMID- 27680933 TI - Imaging techniques: MRI illuminated by gamma-rays. PMID- 27680934 TI - Microbiology: The bacterial cell wall takes centre stage. PMID- 27680935 TI - Biogeochemistry: Long-term effects of permafrost thaw. PMID- 27680936 TI - Physiology: Forecast for water balance. PMID- 27680937 TI - Chemistry: Small molecular replicators go organic. PMID- 27680938 TI - A method for imaging and spectroscopy using gamma-rays and magnetic resonance. AB - Magnetic resonance imaging (MRI) provides fine spatial resolution, spectral sensitivity and a rich variety of contrast mechanisms for diagnostic medical applications. Nuclear imaging using gamma-ray cameras offers the benefits of using small quantities of radioactive tracers that seek specific targets of interest within the body. Here we describe an imaging and spectroscopic modality that combines favourable aspects of both approaches. Spatial information is encoded into the spin orientations of tiny amounts of a polarized radioactive tracer using pulses of both radio-frequency electromagnetic radiation and magnetic-field gradients, as in MRI. However, rather than detecting weak radio frequency signals, imaging information is obtained through the detection of gamma rays. A single gamma-ray detector can be used to acquire an image; no gamma-ray camera is needed. We demonstrate the feasibility of our technique by producing images and spectra from a glass cell containing only about 4 * 10(13) atoms (about 1 millicurie) of the metastable isomer (131m)Xe that were polarized using the laser technique of spin-exchange optical pumping. If the cell had instead been filled with water and imaged using conventional MRI, then it would have contained more than 10(24) water molecules. The high sensitivity of our modality expands the breadth of applications of magnetic resonance, and could lead to a new class of radioactive tracers. PMID- 27680939 TI - Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions. AB - Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate-thioester exchange, thiolate-disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems. PMID- 27680942 TI - Large-scale tissue clearing (PACT): Technical evaluation and new perspectives in immunofluorescence, histology, and ultrastructure. AB - Novel techniques, like CLARITY and PACT, render large tissue specimens transparent and thereby suitable for microscopic analysis. We used these techniques to evaluate their potential in the intestine as an exemplary organ with a complex tissue composition. Immunohistochemistry, light sheet-, and confocal scanning-microscopy enabled us to follow complex three-dimensional structures, like nerve fibers, vessels, and epithelial barriers throughout the entire organ. Moreover, in a systematic electron microscopic study, we analyzed the morphology and preservation of tissue on ultrastructural level during the clearing process. We also connect tissue clearing with classical histology and demonstrate that cleared tissues can be stained with Hematoxylin-Eosin and Heidenhain's Azan stain, suggesting potential use in histopathology. These experiments showed that a neutral pH during the clearing process results in much better preservation of tissue ultrastructure and standard stainability. Volume changes of specimens were monitored and quantified during the course of the protocol. Additionally, we employed the technique to visualize the enteric nervous system and the epithelial barrier in post mortem human gut preparations. Our data show the high potential of tissue clearing throughout different tissue types supporting its usefulness in research and diagnosis, and contribute to the technical discussion of ultrastructural tissue-retention. PMID- 27680940 TI - Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep. AB - Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle. Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock drive behavioural rhythms are unknown. Here we show that the sleep period in mice (Zeitgeber time, ZT0-12) is preceded by an increase in water intake promoted entirely by the central clock, and not motivated by physiological need. Mice denied this surge experienced significant dehydration near the end of the sleep period, indicating that this water intake contributes to the maintenance of overnight hydromineral balance. Furthermore, this effect relies specifically on the activity of SCN vasopressin (VP) neurons that project to thirst neurons in the OVLT (organum vasculosum lamina terminalis), where VP is released as a neurotransmitter. SCN VP neurons become electrically active during the anticipatory period (ZT21.5-23.5), and depolarize and excite OVLT neurons through the activation of postsynaptic VP V1a receptors and downstream non-selective cation channels. Optogenetic induction of VP release before the anticipatory period (basal period; ZT19.5-21.5) excited OVLT neurons and prompted a surge in water intake. Conversely, optogenetic inhibition of VP release during the anticipatory period inhibited the firing of OVLT neurons and prevented the corresponding increase in water intake. Our findings reveal the existence of anticipatory thirst, and demonstrate this behaviour to be driven by excitatory peptidergic neurotransmission mediated by VP release from central clock neurons. PMID- 27680943 TI - Recognizing young children with high potential: U-STARS~PLUS. AB - Hands-on science is the ideal platform for observing young children's ability to solve problems, think deeply, and use their creative ingenuity to explore the world around them. Science is naturally interesting and offers authentic reasons to read for information and use math skills to collect, compile, and analyze data. This chapter will share one approach to nurturing and recognizing young children with high-potential: U-STARS~PLUS (Using Science, Talents, and Abilities to Recognize Students~Promoting Learning for Underrepresented Students). Each of the five components (high-end learning environments; teacher's observations of potential; engaging science activities; partnerships with parents; and capacity building for system change) will be explained. Concrete examples will be given for each area showing how it works and why it is important. Special attention will be paid to the needs of educationally vulnerable gifted children who remain underserved: racially, ethnically, and linguistically different; economically disadvantaged, and children who are twice exceptional (2e). PMID- 27680944 TI - Using laser capture microdissection to study fiber specific signaling in locomotor muscle in COPD: A pilot study. AB - INTRODUCTION: Quadriceps dysfunction is important in chronic obstructive pulmonary disease (COPD), with an associated increased proportion of type II fibers. Investigation of protein synthesis and degradation has yielded conflicting results, possibly due to study of whole biopsy samples, whereas signaling may be fiber-specific. Our objective was to develop a method for fiber specific gene expression analysis. METHODS: 12 COPD and 6 healthy subjects underwent quadriceps biopsy. Cryosections were immunostained for type II fibers, which were separated using laser capture microdissection (LCM). Whole muscle and different fiber populations were subject to quantitative polymerase chain reaction. RESULTS: Levels of muscle-RING-finger-protein-1 and Atrogin-1 were lower in type II fibers of COPD versus healthy subjects (P = 0.02 and P = 0.03, respectively), but differences were not apparent in whole muscle or type I fibers. CONCLUSIONS: We describe a novel method for studying fiber-specific gene expression in optimum cutting temperature compound-embedded muscle specimens. LCM offers a more sensitive way to identify molecular changes in COPD muscle. Muscle Nerve 55: 902-912, 2017. PMID- 27680945 TI - Thermal Ablation of Colorectal Lung Metastases: Retrospective Comparison Among Laser-Induced Thermotherapy, Radiofrequency Ablation, and Microwave Ablation. AB - OBJECTIVE: The purpose of this study is to retrospectively evaluate local tumor control, time to tumor progression, and survival rates among patients with lung metastatic colorectal cancer who have undergone ablation therapy performed using laser-induced thermotherapy (LITT), radiofrequency ablation (RFA), or microwave ablation (MWA). MATERIALS AND METHODS: Data for this retrospective study were collected from 231 CT-guided ablation sessions performed for 109 patients (71 men and 38 women; mean [+/- SD] age, 68.6 +/- 11.2 years; range, 34-94 years) from May 2000 to May 2014. Twenty-one patients underwent LITT (31 ablations), 41 patients underwent RFA (75 ablations), and 47 patients underwent MWA (125 ablations). CT scans were acquired 24 hours after each therapy session and at follow-up visits occurring at 3, 6, 12, 18, and 24 months after ablation. Survival rates were calculated from the time of the first ablation session, with the use of Kaplan-Meier and log-rank tests. Changes in the volume of the ablated lesions were measured using the Kruskal-Wallis method. RESULTS: Local tumor control was achieved in 17 of 25 lesions (68.0%) treated with LITT, 45 of 65 lesions (69.2%) treated with RFA, and 91 of 103 lesions (88.3%) treated with MWA. Statistically significant differences were noted when MWA was compared with LITT at 18 months after ablation (p = 0.01) and when MWA was compared with RFA at 6 months (p = 0.004) and 18 months (p = 0.01) after ablation. The overall median time to local tumor progression was 7.6 months. The median time to local tumor progression was 10.4 months for lesions treated with LITT, 7.2 months for lesions treated with RFA, and 7.5 months for lesions treated with MWA, with no statistically significant difference noted. New pulmonary metastases developed in 47.6% of patients treated with LITT, in 51.2% of patients treated with RFA, and in 53.2% of patients treated with MWA. According to the Kaplan-Meier test, median survival was 22.1 months for patients who underwent LITT, 24.2 months for those receiving RFA, and 32.8 months for those who underwent MWA. The overall survival rate at 1, 2, and 4 years was 95.2%, 47.6%, and 23.8%, respectively, for patients treated with LITT; 76.9%, 50.8%, and 8.0%, respectively, for patients treated with RFA; and 82.7%, 67.5%, and 16.6%, respectively, for patients treated with MWA. The log-rank test revealed no statistically significant difference among LITT, RFA, and MWA. The progression-free survival rate at 1, 2, 3, and 4 years was 96.8%, 52.7%, 24.0%, and 19.1%, respectively, for patients who underwent LITT; 77.3%, 50.2%, 30.8%, and 16.4%, respectively, for patients who underwent RFA; and 54.6%, 29.1%, 10.0%, and 1.0%, respectively, for patients who underwent MWA, with no statistically significant difference noted among the three ablation methods. CONCLUSION: LITT, RFA, and MWA can be used as therapeutic options for lung metastases resulting from colorectal cancer. Statistically significant differences in local tumor control revealed a potential advantage in using MWA. No differences in time to tumor progression or survival rates were detected when the three different ablation methods were compared. PMID- 27680946 TI - H2PO4-- and Solvent-Induced Polymorphism of an Amide-Functionalized [Pt(N^C^N)Cl] Complex. AB - A simple [Pt(N^C^N)Cl] complex functionalized with an amide group was prepared, and its absorption and emission properties were examined in different solvents in response to various anions. On the one hand, in the presence of H2PO4-, the solution of the complex shows distinct color changes in CH3CN, together with a ratiometric emission change from a green emission band at 537 nm to a deep red emission band at 680 nm. On the other hand, two-step spectral changes were observed in response to H2PO4- in CH2Cl2, with the green emission being attenuated first followed by the appearance of enhanced and yellow-green emissions at a lower-energy region. These recognition processes are highly selective for H2PO4- against other common anions including F-, Cl-, Br-, I-, OAc , NO3-, and HSO4-. In addition, the platinum complex displays multistage emission polymorphism in mixed CH3CN/H2O solvent of various ratios. The hydrogen-bonding interaction between H2PO4- and the amide unit was confirmed by NMR analysis. In the solid state, this platinum complex emits red light. However, the composite material of the platinum complex with H2PO4- shows purely monomeric yellow emissions. The solid-state materials were further analyzed by single-crystal X ray and Fourier-transform IR analysis. These studies suggest that this simple platinum complex is useful for the selective recognition of H2PO4- and as solid state emitting materials with tunable emission colors. PMID- 27680948 TI - Quantitatively in Situ Imaging Silver Nanowire Hollowing Kinetics. AB - We report the in situ investigation of the morphological evolution of silver nanowires to hollow silver oxide nanotubes using transmission X-ray microscopy (TXM). Complex silver diffusion kinetics and hollowing process via the Kirkendall effect have been captured in real time. Further quantitative X-ray absorption analysis reveals the difference between the longitudinal and radial diffusions. The diffusion coefficient of silver in its oxide nanoshell is, for the first time, calculated to be 1.2 * 10-13 cm2/s from the geometrical parameters extracted from the TXM images. PMID- 27680949 TI - Correction: Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002549.]. PMID- 27680947 TI - The circadian clock modulates anti-cancer properties of curcumin. AB - BACKGROUND: Curcuminoids of the spice turmeric and their enhanced derivatives have much potential as cancer treatments. They act on a wide variety of biological pathways, including those regulating cell division and circadian rhythms. It is known that circadian clocks can modify cancer therapy effectiveness, according to studies aimed at optimizing treatments based on the circadian cycle. It is therefore important to determine whether treatments with curcumin or similar chemotherapeutic agents are regulated by circadian timing. Similarly, it is important to characterize any effects of curcumin on timing abilities of the circadian clocks within cancer cells. METHODS: We examined the circadian clock's impact on the timing of cell death and cell division in curcumin-treated C6 rat glioma cells through continuous video microscopy for several days. To evaluate its persistence and distribution in cancer cells, curcumin was localized within cell compartments by imaging its autofluorescence. Finally, HPLC and spectroscopy were used to determine the relative stabilities of the curcumin congeners demethoxycurcumin and bisdemethoxycurcumin that are present in turmeric. RESULTS: Circadian rhythms in cell death were observed in response to low (5 MUM) curcumin, reaching a peak several hours before the peak in rhythmic expression of mPER2 protein, a major circadian clock component. These results revealed a sensitive phase of the circadian cycle that could be effectively targeted in patient therapies based on curcumin or its analogs. Curcumin fluorescence was observed in cell compartments at least 24 h after treatment, and the two congeners displayed greater stability than curcumin in cell culture medium. CONCLUSIONS: We propose a mechanism whereby curcuminoids act in a sustained manner, over several days, despite their tendency to degrade rapidly in blood and other aqueous media. During cancer therapy, curcumin or its analogs should be delivered to tumor cells at the optimal phase for highest efficacy after identifying the circadian phase of the cancer cells. We confirmed the greater stability of the curcumin congeners, suggesting that they may produce sustained toxicity in cancer cells and should be considered for use in patient care. PMID- 27680951 TI - Measurement characteristics of the Functional Independence Measure. AB - Clinicians and researchers recognize the need for measures offunctional status that possess linear properties and are reliable and valid. Rasch rating scale analysis provides the means for converting raw scores from functional assessment tools to linear measures for which measurement error can be quantified. The extent to which clinicians perceive patients who are undergoing rehabilitation after stroke as similarto other patient groups was investigated using the Functional Independence Measure (FIM). Earlier work demonstrated that the first 13 items of the FIM represent a measure of motor function and that the last 5 items represent a measu re of cognitive function. The FIM was used for patients with stroke in a manner similar to that for most other impairment groups on the motor items. Patients with stroke were, however, unlike many impairment groups in their ratings on the cognitive items. Tables showing raw score to scaled measure conversions are provided for two sets of impairment groups on the motor items and three sets of impairment groups on the cognitive items. Clinicians can be confident that the measures derived from the FIM are linear across the range of the instrument and are attuned to the uniqueness of patients with stroke and other specific impairments. PMID- 27680952 TI - Functional assessment in a community setting. AB - Functional assessment for persons with disabilities has been an important component of the traditional inpatient rehabilitation process. Recently there has been increasing interest in functional assessment for persons residing in the community as a means to understanding the role of rehabilitation in community integration and the effects of aging on persons with disabilities. The instruments used for in-hospital functional assessment (e.g., the Functional Independence Measure and the Barthel Index) measure aspects of disability, specifically basic self-care and mobility skills, and may not be adequate for community assessment. Most often the functional activities that are of interest for persons I iving in the community include instrumental activities of daily living such as housekeeping and shopping; components of handicap such as social integration, community mobility, and productive use of time; and community participation. Instruments used to measure components of handicap (i.e., the Craig Handicap Assessment and Reporting Technique) and community participation (i.e., the Self-Observation and Report Technique) may be more appropriate for the evaluation of functional status for persons living in the community. PMID- 27680953 TI - Predicting outcome after acute stroke with the Functional Independence Measure. AB - Previous studies attempting to predict outcome after acute stroke have been limited by small sample sizes and inconsistent definitions of outcome. The functional status data from the Functional Independence Measure (FIM) as well as social and demographic information from 2,109 stroke survivors were reviewed to determine the possible risk factors for poor outcome. Four measures of outcome were used for this analysis: discharge placement, rate of change of functional status as measured by the FIM, total change in functional status from admission to discharge, and length of stay. The most significant risk factor for discharge to a location other than home was an admission FIM score of less than 60; the relative risk was 3.5. Several other factors, including race, marital status, and age, influenced this outcome. A low admission FIM score was also a significant risk factor for a low rate of change of functional status during the inpatient rehabilitation stay; the relative riskwas 2.2. A low admission FIM score was the most predictive factor but still enabled only poor prognostication for an individual patient. PMID- 27680954 TI - Function-based classification for stroke rehabilitation and issues of reimbursement: Using patient classification systems to scale payment to patient complexity. AB - The Functional Independence Measure-Function Related Groups (FIM-FRGs) classify stroke patients into five clinical categories that predict medical rehabilitation length of stay as a proxy for cost. The current payment system for inpatient rehabilitation does not adjust for clinical complexity, thus potentially leading to care inequities for individual patients and unequal distribution of resources among rehabilitation facilities. Designed for use as part of a payment system, the FIM-FRGs could operate within the Tax Equity and Fiscal Responsibility Act payment system or other payment systems to adjust for the clinical complexity of the patients actually treated. The article discusses the use of function-based classification schemes for the payment of stroke rehabilitation. PMID- 27680950 TI - Molecular bases of K+ secretory cells in the inner ear: shared and distinct features between birds and mammals. AB - In the cochlea, mammals maintain a uniquely high endolymphatic potential (EP), which is not observed in other vertebrate groups. However, a high [K+] is always present in the inner ear endolymph. Here, we show that Kir4.1, which is required in the mammalian stria vascularis to generate the highly positive EP, is absent in the functionally equivalent avian tegmentum vasculosum. In contrast, the molecular repertoire required for K+ secretion, specifically NKCC1, KCNQ1, KCNE1, BSND and CLC-K, is shared between the tegmentum vasculosum, the vestibular dark cells and the marginal cells of the stria vascularis. We further show that in barn owls, the tegmentum vasculosum is enlarged and a higher EP (~+34 mV) maintained, compared to other birds. Our data suggest that both the tegmentum vasculosum and the stratified stria vascularis evolved from an ancestral vestibular epithelium that already featured the major cell types of the auditory epithelia. Genetic recruitment of Kir4.1 specifically to strial melanocytes was then a crucial step in mammalian evolution enabling an increase in the cochlear EP. An increased EP may be related to high-frequency hearing, as this is a hallmark of barn owls among birds and mammals among amniotes. PMID- 27680955 TI - Constraints on predicting functional recovery after stroke: Application of clinical, laboratory, neurophysiologic, and neuroimaging parameters. AB - Methodologic issues in statistical prediction of functional outcome from stroke are considered, and a model that defines various sources of constraint on the processes involved in recovery is elaborated. Prediction is relatively easy for the upper and lower bands of stroke survivors but becomes significantly more complex forthe middle band of patients, for whom inpatient rehabilitation services may be considered potentiallycost effective. Sources of constraint on functional outcome include biological factors related to the stroke and to comorbid medical conditions, cognitive factors related to higher cortical functions impaired by the stroke, premorbid personality and emotional response factors, and socioeconomic factors such as the availability of a social support system. In examining recovery of function at the impairment level, issues related to how various functions in the brain are reorganized after injury become important. New information about the capacity of functional brain subsystems to reorganize after focal damage due to stroke may help improve the ability to generate prognoses and may also guide the development and application of rehabilitation strategies. PMID- 27680956 TI - Alternatives to traditional practices. PMID- 27680958 TI - A change for the better! PMID- 27680957 TI - A question of decision-making capacity. PMID- 27680960 TI - From the editor. PMID- 27680962 TI - Letters to the editors. PMID- 27680961 TI - Foreword. PMID- 27680963 TI - Prenatal food restriction induces poor-quality articular cartilage in female rat offspring fed a post-weaning high-fat diet and its intra-uterine programming mechanisms. AB - Epidemiological data show that osteoarthritis (OA) is significantly associated with lower birth weight, and that OA may be a type of fetal-originated adult disease. The present study aimed to investigate the prenatal food-restriction (PFR) effect on the quality of articular cartilage in female offspring to explore the underlying mechanisms of fetal-originated OA. Maternal rats were fed a restricted diet from gestational day (GD) 11 to 20 to induce intra-uterine growth retardation. Female fetuses and female adult offspring fed a post-weaning high fat diet were killed at GD20 and postnatal week 24, respectively. Serum and knee cartilage samples from fetuses and adult female offspring were collected and examined for cholesterol metabolism and histology. Fetal serum corticosterone and insulin-like growth factor-1 (IGF-1) in the PFR group were lower than those of the control, but the serum cholesterol level was not changed. The lower expression of IGF-1 in the PFR group lasted into adulthood. The expression of extracellular matrix (ECM) genes, including type II collagen, aggrecan and cholesterol efflux genes including liver X receptor, were significantly induced, but the ATP-binding-cassette transporter A1 was unchanged. PFR could induce a reduction in ECM synthesis and impaired cholesterol efflux in female offspring, and eventually led to poor quality of articular cartilage and OA. PMID- 27680965 TI - Resection of central nervous system lymphoma (CNSL): a paradigm shift? AB - BACKGROUND: Central nervous system lymphomas (CNSL) are traditionally regarded as non-surgically treated tumors with a poor prognosis. Usually, only stereotactic biopsy is performed to establish the diagnosis, and most patients show disease progression within half a year. A recent study questioned this view, since patients who had surgical resection of PCNSL manifestations prior to adjuvant therapy reportedly had a better outcome than patients who had biopsy only. METHODS: We performed a retrospective analysis of our patient database to identify patients with CNSL who had undergone "accidental" tumor removal in our department between 2002 and 2013. Four patients had CNSL specific therapy following surgery. One patient received no further therapy because of his bad clinical status. RESULTS: Five patients with CNSL were treated surgically. Three patients were in complete remission at nine, thirteen and 45 months postoperatively, while two others had disease progression at 45 months, respectively. The median survival was 22.6 months. CONCLUSION: Gross total removal of CNSL may improve outcome. We present a series of five patients who had surgical resection of CNSL. While the importance of chemotherapy is beyond doubt, more data on the effect of surgery on the prognosis of patients with CNSL are needed. However, the paradigm of medical treatment only for CNSL is being challenged. PMID- 27680964 TI - Inequalities in energy-balance related behaviours and family environmental determinants in European children: changes and sustainability within the EPHE evaluation study. AB - BACKGROUND: Increasing social inequalities in health across Europe are widening the gap between low and high socio-economic groups, notably in the prevalence of obesity. Public health interventions may result in differential effects across population groups. Therefore, the EPHE (EPODE for the Promotion of Health Equity) project analysed the added value of community-based programmes, based on the EPODE (Ensemble Prevenons l'Obesite Des Enfants-Together Let's Prevent Obesity) model, to reduce socio-economic inequalities in energy balance-related behaviours of children and their family-environmental related determinants in seven European communities. This study presents the changes between baseline and follow-up after the one-year interventions and their sustainability one year after. METHODS: This is a prospective study with a one school-year intervention, followed by one year of follow-up. In all, 1266 children (age 6-8 years) and their families from different socio-economic backgrounds were recruited at baseline. For 1062 children, information was available after one year (T1) and for 921 children after two years (T2). A self-reported questionnaire was completed by the parents to examine the children's energy balance-related behaviours and family- environmental determinants. Socio-economic status was defined by the educational level of the mother. The Wilcoxon signed-rank test for paired data was used to test the differences between baseline and intermediate, and between intermediate and final, measurements for each of the socio-economic status groups. RESULTS: Post-intervention effects in energy-balance related behaviours showed the following improvements among the low socio-economic status groups: increased fruit consumption (Netherlands), decreased fruit juices amount consumed (Romania) and decreased TV time on weekdays (Belgium). Whereas in only the latter case the behavioural change was accompanied with an improvement in a family-environmental determinant (monitoring the time the child watches TV), other improvements in parental rules and practices related to soft drinks/fruit juices and TV exposure were observed. A few of those effects were sustainable, notably in the case of Belgium. CONCLUSIONS: Inequalities in obesity-related behaviours could be potentially reduced when implementing community-based interventions, tailored to inequality gaps and using the EPODE methodology. Within-group changes varied widely, whereas monitoring of interventions and process evaluation are crucial to understand the observed results. PMID- 27680966 TI - Second line treatment of recurrent glioblastoma with sunitinib: results of a phase II study and systematic review of literature. AB - INTRODUCTION: Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib (S) plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with S in this setting published to date and summarized it in a meta-analysis. EVIDENCE ACQUISITION: Patients with GBM recurrent or progressive after surgery and standard chemo radiotherapy were treated with S 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. EVIDENCE SYNTHESIS: Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI 10.3 28.1) in the weekly setting which was consistent across all the studies (I2 0%, p = 0.66) and a pooled 6-PFS of 12.7% (95% CI 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2 65%, p = 0.01). CONCLUSIONS: Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, S has insufficient activity in the setting of recurrent GBM. Better patient's molecular stratification for second line treatment in GBM is warranted. PMID- 27680967 TI - Ventriculitis and multicompartimental hydrocephalus: a new endoscopic goal. PMID- 27680970 TI - The lord of the broken rings: African porocephaliasis, an emerging radiological diagnosis in developed countries. PMID- 27680971 TI - [Long-term results after prostate vaporisation : GreenLightTM laser vaporisation of the prostate and electrovaporisation]. AB - BACKGROUND: Various minimally invasive techniques are available for the surgical treatment of benign prostatic obstruction. Besides resection and enucleation, vaporization of the prostate is an attractive alternative. OBJECTIVES: The aim of the present article is to provide a comprehensive literature review on long-term results of GreenLightTM laser vaporisation and electrovaporisation of the prostate. MATERIALS AND METHODS: A literature search on long-term (>=5 years) results of GreenLightTM laser vaporization of the prostate and electrovaporisation of the prostate. RESULTS: Laser vaporization of the prostate with the GreenLightTM laser leads to an immediate and long-lasting improvement of voiding symptoms beyond 5 years. Currently, no long-term data of the 180 W laser model are available. With the former 80 W laser, an increased rate of reoperation due to recurrent obstruction has been described. As reoperation mainly occurs within the first 2 postoperative years, this suggests insufficient tissue ablation. Electrovaporisation of the prostate also leads to an improvement of voiding symptoms. However, only few studies on long-term results are available which report a relatively high rate of treatment failure. In addition, these studies have limitations in study design. CONCLUSIONS: Laser vaporisation of the prostate with the GreenLightTM laser seems to be an effective minimally invasive treatment alternative for BPO. However, long-term results of the current 180 W laser are still awaited. Based on limited data, electrovaporisation of the prostate currently cannot be recommended as an established treatment alternative. PMID- 27680968 TI - Dynamics of nuclear receptor gene expression during Pacific oyster development. AB - BACKGROUND: Nuclear receptors are a highly conserved set of ligand binding transcription factors, with essential roles regulating aspects of vertebrate and invertebrate biology alike. Current understanding of nuclear receptor regulated gene expression in invertebrates remains sparse, limiting our ability to elucidate gene function and the conservation of developmental processes across phyla. Here, we studied nuclear receptor expression in the early life stages of the Pacific oyster, Crassostrea gigas, to identify at which specific key stages nuclear receptors are expressed RESULTS: We used quantitative RT-PCR to determine the expression profiles of 34 nuclear receptors, revealing three developmental key stages, during which nuclear receptor expression is dynamically regulated: embryogenesis, mid development from gastrulation to trochophore larva, and late larval development prior to metamorphosis. Clustering of nuclear receptor expression patterns demonstrated that transcriptional regulation was not directly related to gene phylogeny, suggesting closely related genes may have distinct functions. Expression of gene homologs of vertebrate retinoid receptors suggests participation in organogenesis and shell-formation, as they are highly expressed at the gastrulation and trochophore larval initial shell formation stages. The ecdysone receptor homolog showed high expression just before larval settlement, suggesting a potential role in metamorphosis. CONCLUSION: Throughout early oyster development nuclear receptors exhibited highly dynamic expression profiles, which were not confined by gene phylogeny. These results provide fundamental information on the presence of nuclear receptors during key developmental stages, which aids elucidation of their function in the developmental process. This understanding is essential as ligand sensing nuclear receptors can be disrupted by xenobiotics, a mode of action through which anthropogenic environmental pollutants have been found to mediate effects. PMID- 27680972 TI - [Transurethral resection of the prostate]. AB - Symptoms related to benign prostatic hyperplasia (BPH) are the most common reason why patients consult a urologist. Despite the rise of new minimally invasive technologies, transurethral resection of the prostate (TURP) remains the most commonly used procedure (at 84 %) to treat BPH patients in Germany. The continued popularity of this procedure can be explained by three main reasons: a robust, simple technique, an until now unsurpassed efficacy and-with regard to the risk benefit ratio-a low morbidity. Following TURP, the mean Qmax is 19-20 ml/s and the mean IPSS is 6. BPH recurrence occurs in 2-7 % of patients within 8-22 years following TURP. Regarding clinical efficacy, meta-analyses now show relevant differences between monopolar and bipolar (B) TURP. However, B-TURP seems to be favourable considering potential complications. Clot retention with an incidence of 1-5 % is the most common acute complication and urethral strictures with an incidence of 2-9 % are the most common long-term complications of TURP. TUR syndrome is nowadays a clinical rarity. However, many complications can be avoided by a proper resection technique. TURP is still the standard in surgical BPH therapy. PMID- 27680969 TI - Effects of diode laser (980 nm) on orthodontic tooth movement and interleukin 6 levels in gingival crevicular fluid in female subjects. AB - The aim of this study was to evaluate the effects of low-level laser irradiation on the rate of orthodontic tooth movement (OTM) and the interleukin-6 (IL-6) concentration in gingival crevicular fluid (GCF) during orthodontic treatment. In this randomized split-mouth double blind clinical trial, 11 female patients aged 14 to 25 years (mean 19 +/- 4.21 year), who required canine retraction following four first premolars extraction, were selected. The GaAlAs laser diode laser (A.R.C. Laser GmbH, Nurnberg, Germany) (980 nm, 100 mW, 5.6 J/cm2, three points from the buccal side and three from lingual side of the tooth, 56 s, running in continuous mode) was used for canine retraction in only one maxillary quadrant (LG). The irradiation time for each cervical and middle third of the tooth was 10 s, and 8 s for the apical third of the tooth. The other maxillary quadrant served as the control group (CG) using the laser pseudo-application in this side. The laser irradiation was applied on days 0, 7, 14, 21, and 28 of each month during the canine retraction phase. Canine retraction was done using closed coil spring with 150 g force on rectangular wires after the alignment and leveling. This study was done in 11 months. Dental casts were made at different time points during the treatment, and the amount of tooth movement was measured. To evaluate the levels of IL-6, GCF samples were collected from the distal side of the maxillary canine teeth on both quadrants at the beginning of the trial, the end of aligning phase, and on day 21 of each month during canine retraction. Although the mean rate of canine retraction was higher in the LG (0.013) than the CG (0.012) and there was definitely a tendency for more canine retraction in the LLLI, but the results failed to show any significant difference between the mean rate of canine retraction of both groups (P = 0.068). A paired t test showed that there was no significant difference in the mean concentration of IL-6 at various stages of the treatment between the groups during canine distalization (P > 0.05). Therefore, conclusive evidence could not be provided to support the efficacy of the diode laser (980 nm) in accelerating OTM in female subject. PMID- 27680973 TI - Local Electronic Structure in gamma-LiAlO2 Studied by Single-Crystal 27Al NMR and DFT Calculations. AB - From single-crystal 27Al NMR experiments, the full tensors for both the electrical field gradient (EFG) and the chemical shift (CS) for the aluminum atoms in gamma-LiAlO2 have been determined. A simultaneous fit of the quadrupolar splittings observed for the four 27Al in the unit cell gave the EFG tensor in the crystal frame, from which a quadrupolar coupling constant of chi = CQ = 3.330 +/- 0.005 MHz and an asymmetry parameter of etaQ = 0.656 +/- 0.002 were derived. The experimentally determined quadrupolar splittings were sufficiently sensitive to quantify small deviations of both rotation axis direction and starting direction by the data fitting routine. For determination of the CS tensor, the evolution of the outer satellite centers over the crystal rotation was tracked, and the contribution of the quadrupolar shift was subtracted according to the previously determined EFG tensor. The resulting CS tensor of 27Al yields an isotropic chemical shift of deltaiso = 81.8 +/- 0.25 ppm and an asymmetry parameter of etaCS = 0.532 +/- 0.004, in good agreement with the fit of a MAS NMR spectrum acquired at B0 = 21.1 T. From both experiments and DFT calculations using the Castep code, we find the eigenvectors of the EFG and CS tensors to be practically colinear. PMID- 27680975 TI - Ag and Cu Monometallic and Ag/Cu Bimetallic Nanoparticle-Graphene Composites with Enhanced Antibacterial Performance. AB - Increased proliferation of antimicrobial resistance and new strains of bacterial pathogens severely impact current health, environmental, and technological developments, demanding design of novel, highly efficient antibacterial agents. Ag, Cu monometallic and Ag/Cu bimetallic nanoparticles (NPs) were in situ grown on the surface of graphene, which was produced by chemical vapor deposition using ferrocene as precursor and further functionalized to introduce oxygen-containing surface groups. The antibacterial performance of the resulting hybrids was evaluated against Escherichia coli cells and compared through a series of parametrization experiments of varying metal type and concentration. It was found that both Ag- and Cu-based monometallic graphene composites significantly suppress bacterial growth, yet the Ag-based ones exhibit higher activity compared to that of their Cu-based counterparts. Compared with well-dispersed colloidal Ag NPs of the same metal concentration, Ag- and Cu-based graphene hybrids display weaker antibacterial activity. However, the bimetallic Ag/CuNP-graphene hybrids exhibit superior performance compared to that of all other materials tested, i.e., both the monometallic graphene structures as well as the colloidal NPs, achieving complete bacterial growth inhibition at all metal concentrations tested. This striking performance is attributed to the synergistic action of the combination of the two different metals that coexist on the surface as well as the enhancing role of the graphene support. PMID- 27680974 TI - ADHD symptoms in non-treatment seeking young adults: relationship with other forms of impulsivity. AB - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) has been associated with various manifestations of impulsivity in adults, including elevated rates of other impulsive disorders, substance use, questionnaire-based impulsivity scores, and inhibitory dysregulation on neurocognitive tests. The relationship between ADHD and all these other forms of impulsivity has yet to be explored within the context of a single comprehensive study. METHODS: A total of 423 young adults, who gambled >=5 times in the preceding year, were recruited using media advertisements and undertook detailed assessment including structured psychiatric interview, questionnaires, and neurocognitive tests. Participants with ADHD symptoms were identified using the Adult ADHD Self-Report Scale Screener (ASRS V1.1) and were compared to controls using multivariate analysis of variance (MANOVA). RESULTS: ADHD symptoms were found in 20.3% of the sample, but only 7.3% of these subjects had ever received a formal diagnosis. ADHD symptoms were associated with significantly lower quality of life, lower self-esteem, higher emotional dysregulation, higher impulsivity questionnaire scores, more problematic Internet use, greater occurrence of psychiatric disorders, and impaired stop-signal reaction times. Of these variables, stop-signal reaction times and Barratt attentional impulsiveness were the strongest predictors of group classification. CONCLUSIONS: ADHD symptoms are common and under-diagnosed in young adults who gamble, and are most strongly linked with certain other types of impulsivity (questionnaire- and cognitive-based measures) and with emotional dysregulation, suggesting that these are each important considerations in understanding the pathophysiology of the disorder, but also potential treatment targets. It is necessary to question whether treatment for adult ADHD could be enhanced by considering self-esteem, emotional reactivity, and impaired inhibitory control as specific treatment targets, in addition to the core diagnostic symptoms of the disorder. PMID- 27680976 TI - miRNAs in non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver cirrhosis and hepatocellular carcinoma and is a considerable threat to public health. miRNAs are important post-transcriptional regulators of gene expression, and the dysregulation of miRNAs is involved in various biological processes in the liver, including lipid homeostasis, inflammation, apoptosis, and cell proliferation. Recently, a number of studies have described the association between miRNAs and NAFLD progression and have shown that circulating miRNAs reflect histological changes in the liver. Therefore, circulating miRNAs have potential use for the evaluation of NAFLD severity. In this review, we discuss the involvement of miRNAs in NAFLD pathogenesis and the key role of miRNAs in the screening, diagnosis, and staging of NAFLD. PMID- 27680977 TI - Antidepressant-like effects of acupuncture involved the ERK signaling pathway in rats. AB - BACKGROUND: The extracellular signal-regulated kinase (ERK) signaling pathway is considered to be associated with the pathogenesis and treatment of depression. Acupuncture has been demonstrated to ameliorate depression-related behavior and promote neurogenesis. In this study, we explored the role of the ERK signaling pathway in the antidepressant-like effects of acupuncture in rats exposed to chronic unpredictable mild stress (CUMS). METHODS: Eighty male Sprague-Dawley rats were randomly divided into eight groups: control group, model group, model + Acupuncture group (Acu group), model + fluoxetine group (FLX group), model + DMSO group (DMSO group), model + PD98059 group (PD group), model + Acupuncture + PD98059 group (Acu + PD group) and model + fluoxetine + PD98059 group (FLX + PD group). Except for the control group, all rats were subjected to 3 weeks of CUMS protocols to induce depression. Acupuncture was carried out for 10 min at acupoints of Baihui (GV-20) and Yintang (GV-29) each day during the experimental procedure. The ERK signaling pathway was inhibited using PD98059 through intracerebroventricular injection. The depression-like behaviors were evaluated using the sucrose intake and open-field tests. The protein levels of ERK1/2, phosphor (p)-ERK1/2, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined using western blot. RESULTS: Acupuncture ameliorated the depression-like behaviors and dysfunction of the ERK signaling pathway in the hippocampus of CUMS rats. PD98059 pretreatment inhibited the improvements brought about by acupuncture on the ERK signaling pathway. CONCLUSIONS: Taken together, our results indicated that acupuncture had a significant antidepressant-like effect on CUMS-induced depression model rats, and the ERK signaling pathway was implicated in this effect. PMID- 27680979 TI - Effects of estradiol on measurements of conduit artery endothelial function after ischemia and reperfusion in premenopausal women. AB - In premenopausal women, ovarian steroids are felt to play a role in the prevention of cardiovascular disease. We aimed to assess whether menstrual cycle variations in estrogen can modify the response to ischemia-reperfusion (IR) injury in humans. In an investigator-blinded crossover study, 10 healthy premenopausal women with regular menstrual cycles were studied. They had flow mediated dilatation (FMD) measured by ultrasound in the radial artery before and after IR (15 min of brachial artery ischemia, 15 min of reperfusion) during both the early and late follicular phases of the menstrual cycle. The order of these visits was not randomized. IR significantly blunted FMD in the early follicular phase (pre-IR: 7.1% +/- 1.0%; post-IR: 3.6% +/- 1.0%, P = 0.01) when estradiol levels were low (148.4 +/- 19.8 pmol/L). Conversely, FMD was preserved after IR during the late follicular phase (pre-IR: 7.2% +/- 0.9%; post-IR: 7.0% +/- 0.8%, P = NS, P = 0.03 compared with early follicular) when estradiol levels were high (825.7 +/- 85.8 pmol/L, P < 0.001 compared with early follicular). There was a significant inverse relationship between estradiol concentration and IR-induced endothelial dysfunction (i.e., change in FMD after IR) (r = 0.59, r2 = 0.36, P < 0.01). These findings demonstrate, for the first time in humans, a clear relationship between the cyclical changes in serum concentrations of estradiol and the endothelium's response to IR. PMID- 27680980 TI - Pre-emptive antibiotic therapy to reduce ventilator-associated pneumonia: "thinking outside the box". AB - Mechanically ventilated, intubated patients are at increased risk for tracheal colonization with bacterial pathogens that may progress to heavy bacterial colonization, ventilator-associated tracheobronchitis (VAT), and/or ventilator associated pneumonia (VAP). Previous studies report that 10 to 30 % of patients with VAT progress to VAP, resulting in increased morbidity and significant acute and chronic healthcare costs. Several natural history studies, randomized, controlled trials, and a meta-analysis have reported antibiotic treatment for VAT can reduce VAP, ventilator days, length of intensive care unit (ICU) stay, and patient morbidity and mortality. We discuss early diagnostic criteria, etiologic agents, and benefits of initiating, early, appropriate intravenous or aerosolized antibiotic(s) to treat VAT and reduce VAP, to improve patient outcomes by reducing lung damage, length of ICU stay, and healthcare costs. PMID- 27680978 TI - Gli1, a potential regulator of esophageal cancer stem cell, is identified as an independent adverse prognostic factor in esophageal squamous cell carcinoma. AB - PURPOSE: The hedgehog (Hh) pathway is involved in cancer stem cell (CSC) maintenance in various tumors. Glioma-associated oncogene homolog 1 (Gli1) is a key mediator of the Hh pathway; however, its expression and clinical significance in esophageal squamous cell carcinoma (ESCC) have not been reported. In this study, we aimed to reveal clinical significance of Gli1 expression in ESCC and further investigate the potential of Gli1 as a CSC regulator of ESCC by comparing its expression with expressions of other stemness genes in ESCC. METHODS: We assessed the expressions of Gli1, Sox9, CD44, Sox2, LSD1, and Oct4 in 127 patients' tissue specimens of ESCC using immunohistochemistry and in ESCC cell lines using Western blotting. The relationship of Gli1 expression with clinic pathologic parameters as well as cell-cycle-regulating genes was investigated. We also investigated the biological pathways that are activated in Gli1-high ESCC using The Cancer Genome Atlas (TCGA) data. RESULTS: Gli1 expression was observed in 28.3 % of ESCC, and its expression was correlated with the expression of stemness genes, Sox9 (P = 0.003) and CD44 (P = 0.012). And Gli1, CD44, and Sox9 were highly expressed in more poorly differentiated ESCC cell lines such as TE8 and TE1 cells. Notably, Gli1 expression was positively associated with distant metastasis (P = 0.011), increased microvessel density (MVD) (P = 0.002), and expression of cell cycle regulators such as p21, cyclin D1, cyclin E1, and NF kappaB (P < 0.05). Sox9 and CD44 expressions in ESCC were also significantly associated with unfavorable clinic-pathologic parameters such as increased MVD, advanced tumor (pT) stage, and higher TNM stage. Moreover, all three potential CSC markers such as Gli1, Sox9, and CD44 were strongly linked to worse clinical outcome and independent poor prognostic factors in overall survival and disease free survival in ESCC. Gene set enrichment analysis revealed that the Gli1-high expressing ESCC patients' group was strongly enriched for gene expression signature of Hh signaling pathway, epithelial-mesenchymal transition, and cancer stem cell. CONCLUSIONS: Targeting Gli1, a potential diagnostic marker of ESCC stem cells, will have a profound therapeutic and prognostic value. PMID- 27680981 TI - Bacteria Are Smartphones and Mobile Genes Are Apps. AB - Bacterial core and accessory genome components are analogous to the operating system and applications of smartphones. The core genome provides stable taxonomy and species lists, but phenotypes reflect the mobile pool of accessory genes. This suggests changes to the ways we define bacterial species and describe bacterial communities. PMID- 27680982 TI - Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis. AB - Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease. PMID- 27680983 TI - Enrichment of dissimilatory Fe(III)-reducing bacteria from groundwater of the Siklos BTEX-contaminated site (Hungary). AB - Dissimilatory iron-reducing bacteria are commonly found in microbial communities of aromatic hydrocarbon-contaminated subsurface environments where they often play key role in the degradation of the contaminants. The Siklos benzene, toluene, ethylbenzene, and xylene (BTEX)-contaminated area is one of the best characterized petroleum hydrocarbon-contaminated sites of Hungary. Continuous monitoring of the microbial community in the center of the contaminant plume indicated the presence of an emerging Geobacter population and a Rhodoferax phylotype highly associated with aromatic hydrocarbon-contaminated subsurface environments. The aim of the present study was to make an initial effort to enrich Rhodoferax-related and other dissimilatory iron-reducing bacteria from this environment. Accordingly, four slightly different freshwater media were used to enrich Fe(III) reducers, differing only in the form of nitrogen source (organic, inorganic nitrogen or gaseous headspace nitrogen). Although enrichment of the desired Rhodoferax phylotype was not succeeded, Geobacter-related bacteria were readily enriched. Moreover, the different nitrogen sources caused the enrichment of different Geobacter species. Investigation of the diversity of benzylsuccinate synthase gene both in the enrichments and in the initial groundwater sample indicated that the Geobacter population in the center of the contaminant plume may not play a significant role in the anaerobic degradation of toluene. PMID- 27680985 TI - To Be Real or Virtual? That is the Question.... AB - This editorial describes a crossroad that many plastic surgeons face when they have to decide how to manage their career. Level of Evidence V This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27680984 TI - Evaluating social exclusion interventions in university-community partnerships. AB - Most university-community partnerships (UCPs) involve elements of community-level social exclusion interventions. As such, they face substantial challenges in management and evaluation. This paper highlights the central challenges associated with evaluation of UCP and other social exclusion interventions at the community level, and suggests methods to overcome them. The main body of the paper presents a case study based on a four-year action research involving evaluation of a social exclusion intervention initiated and implemented by a UCP in Israel. The case study highlights the challenges faced by the evaluation team, the solutions provided, and the contribution of the evaluation to improvement and accountability. PMID- 27680986 TI - Functioning Among Youth with Comorbid Mood Disorder and Chronic Physical Illness in Public Sector Care. AB - OBJECTIVE: The current study examines parent/caregiver and youth report of psychosocial and health-related functioning among youth served in public systems of care, with mood disorder only, comorbid mood disorder and chronic physical illness, and chronic physical illness only. METHOD: Participants were 539 youths (ages, 11-18; 64% male) with a mood disorder and/or chronic physical illness enrolled in a study of public sector care. Presence of mood disorder was based on youth report on the Diagnostic Interview Schedule for Children-IV. Parents reported whether they had been told by a school or health professional that their child had 1 of 8 categories of chronic physical illnesses. Psychosocial functioning was assessed with the Child Behavior Checklist and Youth Self Report. Parent and child versions of the Child Health Questionnaire assessed health related functioning. Covariates included demographic variables, substance use, mental health service utilization, disruptive behavior disorders, and anxiety disorders. Multivariate analysis of covariances assessed differences on outcome measures among the 3 groups. RESULTS: Parents and youths reported significantly worse psychosocial and health-related functioning for youth with comorbid mood and physical illnesses. Generally, parents reported lower functioning in youth with a physical illness compared with mood disorder, and youth with mood disorders reported lower functioning than those with physical illness. CONCLUSION: Youth with comorbid mood disorder and chronic physical illness experience high levels of impairment. Increased screening of mood disorders in pediatric health settings is warranted. Health systems, clinics, and clinicians should focus on integrating mental and physical health diagnosis and treatment. PMID- 27680988 TI - Contracaecum sp. parasitizing Acestrorhynchus lacustris as a bioindicator for metal pollution in the Batalha River, southeast Brazil. AB - Pollution in aquatic ecosystems due to negative human activities remains a problem in both freshwater and marine environments and is an ongoing subject of research. Several studies have shown that some fish parasites can be used as a tool for biomonitoring because they demonstrate higher metal accumulation capacity compared to their host tissues. However, compared to acanthocephalans, information regarding the absorption mechanisms and accumulation rates in nematodes is relatively limited. Here, we evaluated the potential of larvae Contracaecum sp. (L3) as indicators of contamination by metals by analyzing thirteen element concentrations: magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), barium (Ba), and lead (Pb) in the parasites and host Acestrorhynchus lacustris, using inductively coupled plasma mass spectrometry. Twelve of the thirteen analyzed elements were detected in at least 2-fold higher concentrations (e.g. Ni) and were up to approximately 50-fold higher (e.g. Pb) in parasites than in host tissues, including elements known for their high toxicity (As, Cd, Pb) and those considered to be essential (Cu and Zn). Our results suggest that Contracaecum sp. larvae can be used as bioindicators of metal contamination because even in early stages of development, numerous essential and non-essential elements were accumulated, making this system a useful tool for monitoring polluted environments. PMID- 27680989 TI - Do omega-3 PUFAs affect insulin resistance in a sex-specific manner? A systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Evidence has suggested that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve obesity-induced insulin resistance (IR); however, results from human intervention trials have been equivocal. Recently it has been reported that n-3 PUFA status is inversely associated with type 2 diabetes in women but not in men, suggesting a sex-dependent effect. OBJECTIVE: We aimed to determine whether n-3 PUFA interventions affect IR in a sex-dependent manner. DESIGN: Five databases were searched (Medline, EMBASE, CINAHL, Scopus, and Pre-Medline) for randomized controlled trials. Searches were limited to the English language and to studies with adults aged >18 y. When possible, studies were pooled for a meta analysis. The principle summary measure was the standardized mean difference (SMD) between groups. RESULTS: Thirty-one eligible trials were identified with a total of 1848 participants [men: 45.1%; weighted mean +/- SD age: 52.5 +/- 8.2 y; weighted body mass index (in kg/m2): 28.8 +/- 3.0]. Seven studies were conducted in women, 4 studies were conducted in men, and the remaining studies pooled men and women together. Twenty-six trials were pooled for the meta-analysis (men: n = 2; women: n = 6). With all studies (n = 26) pooled, there was no effect of n-3 PUFA on IR at the group level (SMD: 0.089; 95% CI: -0.105, 0.283; P = 0.367). In trials of >=6 wk, a significant improvement in IR was seen in women (SMD: -0.266; 95% CI: -0.524, -0.007; P = 0.045) but not in men (SMD: 0.619; 95% CI: -0.583, 1.820; P = 0.313). CONCLUSIONS: With this analysis, we provide preliminary evidence of a sex-dependent response of IR to an n-3 PUFA intervention. Additional studies are needed to confirm sex-dependent associations and to elucidate the potential mechanisms that are involved. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015017940. PMID- 27680987 TI - Fermented Fiber Supplements Are No Better Than Placebo for a Laxative Effect. AB - BACKGROUND: Misconceptions about the effects of dietary fiber and 'functional' fiber on stool parameters and constipation persist in the literature. METHODS: A comprehensive literature review was conducted with the use of the Scopus and PubMed scientific databases to identify and objectively assess well-controlled clinical studies that evaluated the effects of fiber on stool parameters and constipation. RESULTS: The totality of well-controlled randomized clinical studies show that, to exert a laxative effect, fiber must: (1) resist fermentation to remain intact throughout the large bowel and present in stool, and (2) significantly increase stool water content and stool output, resulting in soft/bulky/easy-to-pass stools. Poorly fermented insoluble fiber (e.g., wheat bran) remains as discreet particles which can mechanically irritate the gut mucosa, stimulating water & mucous secretion if the particles are sufficiently large/coarse. For soluble fibers, some have no effect on viscosity (e.g., inulin, wheat dextrin) while others form high viscosity gels (e.g., beta-glucan, psyllium). If the soluble fiber is readily fermented, whether non-viscous or gel forming, it has no effect on stool output or stool water content, and has no laxative effect. In contrast, a non-fermented, gel-forming soluble fiber (e.g., psyllium) retains its gelled nature and high water-holding capacity throughout the large bowel, resulting in soft/bulky/easy-to-pass stools. CONCLUSION: When considering a recommendation for a fiber supplement regimen to treat and/or prevent constipation, it is important to consider which fibers have the physical characteristics to exert a laxative effect, and which fiber supplements have rigorous clinical evidence of a significant benefit in patients with constipation. PMID- 27680991 TI - Public health economic evaluation of different European Union-level policy options aimed at reducing population dietary trans fat intake. AB - BACKGROUND: The adverse relation between dietary trans fatty acid (TFA) intake and coronary artery disease risk is well established. Many countries in the European Union (EU) and worldwide have implemented different policies to reduce the TFA intake of their populations. OBJECTIVE: The aim of this study was to assess the added value of EU-level action by estimating the cost-effectiveness of 3 possible EU-level policy measures to reduce population dietary TFA intake. This was calculated against a reference situation of not implementing any EU-level policy (i.e., by assuming only national or self-regulatory measures). DESIGN: We developed a mathematical model to compare different policy options at the EU level: 1) to do nothing beyond the current state (reference situation), 2) to impose mandatory TFA labeling of prepackaged foods, 3) to seek voluntary agreements toward further reducing industrially produced TFA (iTFA) content in foods, and 4) to impose a legislative limit for iTFA content in foods. RESULTS: The model indicated that to impose an EU-level legal limit or to make voluntary agreements may, over the course of a lifetime (85 y), avoid the loss of 3.73 and 2.19 million disability-adjusted life-years (DALYs), respectively, and save >51 and 23 billion euros when compared with the reference situation. Implementing mandatory TFA labeling can also avoid the loss of 0.98 million DALYs, but this option incurs more costs than it saves compared with the reference option. CONCLUSIONS: The model indicates that there is added value of an EU-level action, either via a legal limit or through voluntary agreements, with the legal limit option producing the highest additional health benefits. Introducing mandatory TFA labeling for the EU common market may provide some additional health benefits; however, this would likely not be a cost-effective strategy. PMID- 27680992 TI - The 2015 Dietary Guidelines for Americans is associated with a more nutrient dense diet and a lower risk of obesity. AB - BACKGROUND: Dietary pattern analysis represents a departure from the traditional focus on single foods and nutrients and provides a comprehensive understanding of the role of the diet in chronic disease prevention and etiology. Dietary patterns of Canadians have not been evaluated comprehensively with the use of an updated a priori dietary quality index. OBJECTIVES: We aimed to update the Dietary Guidelines for Americans Adherence Index (DGAI) on the basis of the 2015 Dietary Guidelines for Americans (DGA), to evaluate the construct validity and reliability of the revised index, and to examine whether closer adherence to this index is associated with a lower risk of obesity with or without an accompanying chronic disease. DESIGN: Data from 11,748 participants (>=18 y of age) in the cross-sectional Canadian Community Health Survey cycle 2.2 were used in weighted multivariate analyses. Multinomial logistic regression was used to test the association between diet quality and obesity risk. RESULTS: With the use of principal component analyses, the multidimensionality of the 2015 DGAI was confirmed, and its reliability was shown with a high Cronbach's alpha = 0.75. Moving from the first to the fourth (healthiest) quartile of the 2015 DGAI score, there was a trend toward decreased energy (2492 +/- 26 compared with 2403 +/- 22 kcal, respectively; +/-SE) and nutrients of concern (e.g., sodium), whereas intakes of beneficial nutrients increased (P-trend < 0.05). In the age- and sex adjusted model, a lack of adherence to the 2015 DGA recommendations increased the OR of being unhealthy obese from 1.42 (95% CI: 1.02, 1.99) in quartile 3 to 2.08 (95% CI: 1.49, 2.90) in quartile 2 to 2.31 (95% CI: 1.65, 3.23) in the first quartile of the 2015 DGAI score, compared with the fourth quartile (healthiest) (P-trend < 0.0001). The odds of being obese without a chronic disease (healthy obese) and having a chronic disease without being obese also increased in the lowest DGAI quartile compared with the highest DGAI quartile, albeit not as much as in the unhealthy obese group. CONCLUSION: The 2015 DGAI provides a valid and reliable measure of diet quality among Canadians. PMID- 27680990 TI - Consumption of a flavonoid-rich acai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men. AB - BACKGROUND: Acai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from acai consumption in humans is limited. OBJECTIVE: The objective of the present study was to investigate the effect of acai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. DESIGN: Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m2) of 25 30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an acai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). RESULTS: The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P < 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after acai consumption relative to the control. No significant changes were observed in blood pressure, heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. CONCLUSIONS: In this acute study in overweight men, acai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of acai to health. This trial was registered at clinicaltrials.gov as NCT02292329. PMID- 27680993 TI - Potato consumption and risk of cardiovascular disease: 2 prospective cohort studies. AB - BACKGROUND: Whether consumption of potatoes, which are rich in potassium and have a high glycemic index and glycemic load, is associated with the risk of cardiovascular disease (CVD) is unknown. OBJECTIVE: The aim was to examine the association between potato consumption and risk of total and specific CVD events as well as mortality from CVD in 2 prospective cohorts of Swedish adults, a population with a high consumption of potatoes. DESIGN: Information on potato consumption was available from 69,313 men and women, free of CVD and diabetes, in the Cohort of Swedish Men and the Swedish Mammography Cohort. Nonfatal and fatal cases of CVD diagnosed over 13 y of follow-up were identified by linkage with the Swedish National Patient and Cause of Death Registers. Analyses were conducted by using a Cox proportional hazards regression model, controlled for potential confounders. RESULTS: We ascertained 10,147 major CVD events [myocardial infarction (MI), heart failure (HF), and stroke] and 4003 deaths due to CVD. Total potato consumption was not associated with the risk of major CVD events, specific CVD endpoints, or CVD mortality in either men or women. Multivariable HRs (95% CIs) per an increment of 3 servings/wk of total potato consumption (boiled potatoes, fried potatoes, and French fries) were 1.00 (0.97, 1.02) for major CVD events, 1.01 (0.97, 1.04) for MI, 0.97 (0.93, 1.02) for HF, 1.01 (0.97, 1.05) for stroke, and 0.99 (0.95, 1.03) for CVD mortality. There were no significant trends between the consumption of boiled potatoes, fried potatoes, or French fries and risk of any CVD outcome. CONCLUSION: Potato consumption was not associated with the risk of CVD in this population. The Swedish Mammography Cohort and the Cohort of Swedish Men are registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively. PMID- 27680994 TI - Effect of complementary food supplementation on breastfeeding and home diet in rural Bangladeshi children. AB - BACKGROUND: Complementary food supplements (CFSs) can enhance growth where stunting is common, but substitution for the usual diet may reduce observed benefits. OBJECTIVE: We aimed to characterize dietary diversity from home foods in a CFS efficacy trial and determine whether supplementation reduced breastfeeding frequency or displaced home foods. DESIGN: In a cluster-randomized controlled trial in rural Bangladesh, children (n = 5499) received, for 1 y starting at age 6 mo, periodic child feeding counseling for mothers (control) or counseling plus 1 of 4 CFSs fed as a daily snack. Breastfeeding status and past 24-h diet were assessed at enrollment and every 3 mo thereafter until 18 mo of age. A 7-food group dietary diversity score (DDS) was calculated from home foods only, and a DDS >=4 constituted minimum dietary diversity (MDD). RESULTS: Most children (97%) were breastfed through 18 mo of age, and 24-h breastfeeding frequency did not differ by supplementation group. Child dietary diversity was low; only 51% of children met the MDD by 18 mo. Rice, potatoes, and biscuits (cookies) were the most frequently consumed foods, whereas the legumes, dairy, eggs, and vitamin A-rich fruit and vegetable food groups were each consumed by <50% of children. The odds of meeting the MDD through the consumption of home foods were equal or greater in the supplemented groups compared with the control group at all ages. High socioeconomic status and any maternal education were associated with increased odds of MDD at age 18 mo, whereas child sex and household food security were not associated with MDD. CONCLUSIONS: In a setting where daily complementary food supplementation improved linear growth, there was no evidence that supplementation displaced breastfeeding or home foods, and the supplementation may have improved dietary diversity. Pathways by which supplementation with fortified foods may enhance dietary diversity, such as an improved appetite and increased body size, need elucidation. This trial was registered at clinicaltrials.gov as NCT01562379. PMID- 27680995 TI - Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population. AB - BACKGROUND: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution. OBJECTIVE: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs. DESIGN: In the cross sectional NHANES, serum and red blood cell (RBC) folate were first measured with the use of a radioprotein-binding assay (RPBA) (1988-2006) and, afterwards, with the use of a microbiologic assay (2007-2010). We compared prevalence estimates for assay-matched cutoffs (e.g., with the use of an RPBA cutoff with RPBA data) and assay-mismatched cutoffs (e.g., with the use of microbiologic assay cutoff with RPBA data) for risk of deficiency on the basis of megaloblastic anemia as a hematologic indicator in persons >=4 y of age (e.g., serum folate concentration <7 nmol/L and RBC folate concentration <305 nmol/L derived with the use of a microbiologic assay), possible deficiency on the basis of rising homocysteine as a metabolic indicator in persons >=4 y of age (e.g., serum folate concentration <10 nmol/L and RBC folate concentration <340 nmol/L derived with the use of an RPBA), and insufficiency on the basis of elevated risk of neural tube defects in women 12-49 y old (e.g., RBC folate concentration <906 nmol/L derived with the use of a microbiologic assay). RESULTS: Pre-folic acid fortification (1988-1994), risks of deficiency for assay-matched compared with assay-mismatched cutoffs were 5.6% compared with 16% (serum folate), respectively, and 7.4% compared with 28% (RBC folate), respectively; risks declined postfortification (1999-2006) to <1% compared with <1% (serum folate), respectively, and to <1% compared with 2.5% (RBC folate), respectively. Prefortification (1988-1994), risks of possible deficiency for assay-matched compared with assay-mismatched cutoffs were 35% compared with 56% (serum folate), respectively, and 37% compared with 84% (RBC folate), respectively; risks declined postfortification (1999-2006) to 1.9% compared with 7.0% (serum folate), respectively, and to 4.8% compared with 53% (RBC folate), respectively. Postfortification (2007-2010), risks of insufficiency were 3% (assay matched) compared with 39% (assay mismatched), respectively. CONCLUSIONS: The application of assay-mismatched cutoffs leads to a misinterpretation of folate status. This confusion likely applies to clinical assays because no comparability data are available, to our knowledge. PMID- 27680997 TI - Calcium-dependent microneme protein discharge and in vitro egress of Eimeria tenella sporozoites. AB - Egress is a vital step in the endogenous development of apicomplexan parasites, as it assures the parasites exit from consumed host cells and entry into fresh ones. However, little information has previously been reported on this step of Eimeria spp. In this study, we investigated in vitro egress of Eimeria tenella sporozoites triggered by acetaldehyde. We found that addition of exogenous acetaldehyde induces egress of sporozoites from primary chicken kidney cells (PCKs) and stimulate secretion of E. tenella microneme 2 protein (EtMic 2). Moreover, by using cellular calcium inhibitors, we further proved that these processes were dependent on the intracellular calcium of the parasites. Our findings provide clues to the study of interaction between eimerian parasites and their hosts. PMID- 27680996 TI - Adherence to the Mediterranean diet is associated with better quality of life: data from the Osteoarthritis Initiative. AB - BACKGROUND: The Mediterranean diet has positively influenced various medical conditions, but only a paucity of studies has considered the relation between the Mediterranean diet and quality of life (QOL) among people living in North America. OBJECTIVE: We investigated whether a higher adherence to the Mediterranean diet (aMED) was associated with better QOL and decreased pain, stiffness, disability, and depression in a large cohort of North Americans from the Osteoarthritis Initiative. DESIGN: aMED was evaluated through a validated Mediterranean diet score categorized into quintiles. Outcomes of interest were QOL [assessed with the 12-Item Short-Form Health Outcome Survey (SF-12)]; disability, pain, and stiffness [assessed in both knees with the Western Ontario and McMaster Universities Arthritis Index (WOMAC)]; and depressive symptoms [assessed with the Center for Epidemiologic Studies Depression Scale (CES-D)]. RESULTS: Of the 4470 participants (2605 women; mean age: 61.3 y), those with a higher aMED had significantly more favorable scores on all outcomes investigated (P < 0.0001 for all comparisons). After adjustment for potential confounders in linear regression analyses, a higher aMED was significantly associated with a higher SF-12 physical composite scale value (beta: 0.10; 95% CI: 0.05, 0.15; P < 0.0001), lower WOMAC scores (except for stiffness), and lower CES-D scores (beta: -0.05; 95% CI: -0.09, -0.01; P = 0.01). An adjusted logistic regression analysis, taking as reference those in the 2 highest quintiles of the aMED score, confirmed these findings. CONCLUSION: Higher aMED is associated with better QOL and decreased pain, disability, and depressive symptoms. This trial was registered at clinicaltrials.gov as NCT00080171. PMID- 27680999 TI - Senior consultant warns against indiscriminate closures of emergency departments. PMID- 27681000 TI - Prognostic Implications of Biomarker Assessments in Patients With Type 2 Diabetes at High Cardiovascular Risk: A Secondary Analysis of a Randomized Clinical Trial. AB - Importance: Cardiac biomarkers provide insights into pathophysiologic processes and offer an attractive strategy for the assessment of cardiovascular risk. Objective: To assess the incremental prognostic value of biomarkers that reflect different pathophysiologic processes in patients with type 2 diabetes. Design, Setting, and Participants: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 is a randomized, double-blind, placebo-controlled clinical trial that evaluated the safety of saxagliptin vs placebo in 16 492 outpatients with type 2 diabetes with overt cardiovascular disease (CVD) or multiple risk factors. In this secondary analysis, widely used biomarkers were evaluated to ascertain whether they would provide incremental prognostic value in the risk stratification. Median follow-up was 2.1 years (interquartile range, 1.8-2.3 years). The study was performed from May 10, 2010, to June 15, 2013. Interventions: Randomization to saxagliptin vs placebo in addition to standard care. Main Outcomes and Measures: Concentrations of high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein were analyzed continuously and by established cut points. Cardiovascular death, myocardial infarction, ischemic stroke, and hospitalization for heart failure (HF) were adjudicated by a blinded events committee. Results: Of the 16 492 patients, 5455 (33.1%) were female and 11 037 (66.9%) were male. Mean (SD) age was 65.0 (8.5) years (range, 39-99 years). Baseline biomarkers were measured in 12 310 patients. Elevated levels of each biomarker were associated significantly with increased risk for all cardiovascular end points. When added to clinical variables, biomarkers significantly improved the discrimination and appropriate reclassification of risk. Elevated high-sensitivity troponin T was associated with an increased risk of cardiovascular death (adjusted hazard ratio [AHR], 3.07; 95% CI, 2.35-4.02; P < .001), myocardial infarction (AHR, 2.13; 95% CI, 1.69-2.67; P < .001), and hospitalization for HF (AHR, 3.85; 95% CI, 2.82 5.27; P < .001). Elevated N-terminal pro-B-type natriuretic peptide was also associated with an increased risk of cardiovascular death (AHR, 3.09; 95% CI, 2.46-3.89; P < .001), myocardial infarction (AHR, 1.95; 95% CI, 1.51-2.53; P < .001), and hospitalization for HF (AHR, 3.92; 95% CI, 3.11-4.92; P < .001). Elevated high-sensitivity C-reactive protein was more weakly associated with an increased risk of cardiovascular death (AHR, 1.49; 95% CI, 1.22-1.82; P < .001) and hospitalization for HF (AHR, 1.47; 95% CI, 1.20-1.81; P < .001). Consistent results were seen in patients with or without established CVD. Conclusions and Relevance: A substantial proportion of patients with stable type 2 diabetes with established CVD or multiple clinical risk factors have evidence of ongoing myocardial injury, hemodynamic stress, or systemic inflammation. Biomarker risk stratification thus challenges the traditional differentiation between primary and secondary prevention based simply on clinical history. Strategies to improve risk stratification in patients with type 2 diabetes, with or without CVD, should consider incorporation of biomarker data into standard risk algorithms. Trial Registration: clinicaltrials.gov Identifier: NCT01107886. PMID- 27680998 TI - Arabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling. AB - Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the FORGETTER1 (FGT1) locus, with fgt1 mutants displaying reduced maintenance of heat induced gene expression. FGT1 encodes the Arabidopsis thaliana orthologue of Strawberry notch (Sno), and the protein globally associates with the promoter regions of actively expressed genes in a heat-dependent fashion. FGT1 interacts with chromatin remodelers of the SWI/SNF and ISWI families, which also display reduced heat stress memory. Genomic targets of the BRM remodeler overlap significantly with FGT1 targets. Accordingly, nucleosome dynamics at loci with altered maintenance of heat-induced expression are affected in fgt1. Together, our results suggest that by modulating nucleosome occupancy, FGT1 mediates stress induced chromatin memory. PMID- 27681001 TI - TREATMENT OF VITREOMACULAR TRACTION WITH INTRAVITREAL PERFLUOROPROPANE (C3F8) INJECTION. AB - PURPOSE: To assess the posterior vitreous release rates following a single, office-based intravitreal injection of expansile gas in treating vitreomacular traction. METHODS: Thirty eyes of 29 consecutive patients with symptomatic vitreomacular traction received a single, office-based intravitreal injection of up to 0.3 mL of 100% perfluoropropane (C3F8). RESULTS: Overall, vitreomacular traction release occurred in 25 of 30 eyes by the final follow-up visit (83% final release rate); furthermore, 90% (9 of 10 eyes) with diabetes mellitus released, 83% (5 of 6 eyes) with concurrent epiretinal membrane released, and 83% (5 of 6 eyes) previously treated with ocriplasmin released. Vitreomacular traction release occurred overnight in some patients and was documented on spectral domain optical coherence tomography at an average of 13 days (range, 1 62 days). The phakic release rate was 89% (16 of 18 eyes) versus a 75% pseudophakic release rate (9 of 12 eyes) (P = 0.3173). Ellipsoid zone changes on spectral domain optical coherence tomography occurred in 1 of 30 gas-treated eyes. One patient developed pupillary block. CONCLUSION: Office-based intravitreal injection of C3F8 offers an inexpensive and effective treatment for vitreomacular traction, including for patients who underwent previous ocriplasmin administration and in patients with diabetes mellitus or epiretinal membrane. PMID- 27681002 TI - INFLIXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE UVEITIS RESISTANT TO CONVENTIONAL IMMUNOMODULATORY THERAPY. AB - PURPOSE: To examine the efficacy and safety of infliximab therapy in the treatment for noninfectious intermediate uveitis resistant to conventional immunomodulatory therapy. METHODS: Forty-four eyes of 23 patients with resistant noninfectious intermediate uveitis who were treated with infliximab infusions for a minimum period of 3 months were included. Demographic data, clinical data, and fluorescein angiography and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database between August 2005 and February 2014. Clinical response, improvement in ancillary test findings, and major side effects were evaluated. RESULTS: Nineteen patients (82.6%) achieved remission. The mean duration of treatment to induce remission was 3.99 +/- 3.06 months (range, 2-14.7). Cystoid macular edema was the only complication observed during the course of the treatment in 1 eye (2.27%). One patient (4.3%) developed major side effects. None of the patients developed central or peripheral demyelinating neuropathies or multiple sclerosis. At 6 months after remission, logarithm of the minimum angle of resolution visual acuity (P = 0.006) and central macular thickness (P = 0.03) showed significant improvement in patients who achieved remission. CONCLUSION: A significant number of patients achieved remission on infliximab therapy. The incidence of major side effects in our cohort was low. PMID- 27681003 TI - Seeing the rural healthcare journeys of older adults with atrial fibrillation through a photographic lens. AB - Objectives Obtaining the voices of older adult patients with atrial fibrillation (AF) about their health and healthcare has become increasingly important in providing quality care. The purpose of this study was to understand the unique contributions of photographs in the healthcare journeys of rural living older adults with AF. Methods As part of a larger mixed methods study 10 older adults with AF living in rural communities were recruited through two rural primary care physicians' practices. They were followed over six months through a combination of face-to-face and telephone interviews. Photographs were submitted along with personal journey logs to report healthcare interactions. A photographic analysis was conducted. Results Collectively photos illuminated aspects of older adults AF journeys (stable, chronic unstable, and acute crisis) less explicit in the narrative accounts. Three themes emerged: focus of attention, life-space, and support. Shifts in illness as a focus of attention and life-space paralleled patients at different points in their AF journeys while a range of formal and informal supports were available to them. Discussion Photographs were valuable in shedding light on older adults' rural healthcare experiences. They offer a nuanced approach for gaining insights into the subtleties characterizing the journeys of older adults with AF. PMID- 27681004 TI - Diagnosis of invasive fungal diseases in pediatric patients. AB - INTRODUCTION: The optimal management of invasive fungal infections (IFIs) in children requires prompt and precise diagnosis that enables timely implementation of appropriate antifungal therapy and decreased use of unnecessary toxic antifungals. Areas covered: Traditional approaches such as culture, microscopy and histopathology remain the gold standard but are often not sufficiently sensitive and specific. These limitations have led to the development of alternative non-invasive diagnostic methods that in most cases detect fungal components, such as antigens or nucleic acids. To date, galactomannan and 1,3 beta-D-glucan assays are the most efficient non-culture methods for diagnosis and monitoring of antifungal therapy. New technologies from nano-sciences are applied, like T2Candida assay. However, these are not standardized or validated in children. Herein, we focus on IFI diagnosis emphasizing current perspectives, interpretation difficulties, and need for further evaluation in pediatrics. Expert commentary: The new diagnostic tools may enhance diagnostic capacity in combination with traditional methods. PMID- 27681005 TI - Preventing Posttraumatic Stress Related to Sexual Assault Through Early Intervention: A Systematic Review. AB - Sexual assault survivors come into contact with a variety of community responders after assault, and these interactions may play an important role in mitigating distress. Given theoretical understandings of the importance of early experiences in the development of posttraumatic stress (PTS), early contact with formal systems (e.g., health care, criminal justice, social services) and informal responders (e.g., friends, family) might be particularly important in preventing PTS. However, the effectiveness of these early interventions is unclear. Understanding the key elements of early interventions, both formal and informal, that successfully prevent the development of PTS could help to improve community responses to sexual assault and ultimately promote survivor well-being. In this systematic review, we investigate the types of experiences with responders in the early aftermath of assault that are associated with PTS, the duration of effects on PTS, and the role of the timing of these responses in the development of PTS. Findings indicate that responder contact alone is not typically associated with significant differences in PTS, and there is insufficient evidence to indicate that the timing of seeking help is associated with PTS, but the quality of services provided and perceptions of interactions with certain responders appear to be associated with PTS. Although many effects were short-lived, interventions that were perceived positively may be associated with lower PTS up to a year postassault. These findings support the importance of offering best practice interventions that are perceived positively, rather than simply encouraging survivors to seek help. PMID- 27681006 TI - Antiseptics and Antibiotics for Surgical Wounds Healing by Secondary Intention: Summary of a Cochrane Review. AB - Clinical Question: Do antiseptics and antibiotics benefit surgical wounds healing by secondary intention (SWHSI)? Bottom Line: No high-quality randomized clinical trials have addressed this question. Current evidence is limited and insufficient; it is uncertain whether treating SWHSI with antiseptics or antibiotics is beneficial. PMID- 27681007 TI - Diagnosis of CCSVI in Meniere syndrome. AB - PURPOSE: The authors have evaluated by ultrasound the CCSVI in Meniere's Disease. MATERIALS AND METHODS: 140 patients with diagnosis of Meniere's Disease, who have had not improvement to usual therapy, underwent echo color Doppler sonografy by Zamboni's protocol for the diagnosis of CCSVI . 128 were positive. RESULTS: Ultrasound diagnosis of CCSVI was performed in patients with Meniere's Disease with a positivity in 128 patients on 140 examinated (90% of cases). In healthy population the presence of CCSVI has been evident in 3% of cases. CONCLUSIONS: There is a significant prevalence of CCSVI in patients with Meniere's Disease KEY WORDS: CCSVI, Duplex US, Meniere Disease, Multiple Sclerosis. PMID- 27681008 TI - Using cloud models of heartbeats as the entity identifier to secure mobile devices. AB - Mobile devices are extensively used to store more private and often sensitive information. Therefore, it is important to protect them against unauthorised access. Authentication ensures that authorised users can use mobile devices. However, traditional authentication methods, such as numerical or graphic passwords, are vulnerable to passive attacks. For example, an adversary can steal the password by snooping from a shorter distance. To avoid these problems, this study presents a biometric approach that uses cloud models of heartbeats as the entity identifier to secure mobile devices. Here, it is identified that these concepts including cloud model or cloud have nothing to do with cloud computing. The cloud model appearing in the study is the cognitive model. In the proposed method, heartbeats are collected by two ECG electrodes that are connected to one mobile device. The backward normal cloud generator is used to generate ECG standard cloud models characterising the heartbeat template. When a user tries to have access to their mobile device, cloud models regenerated by fresh heartbeats will be compared with ECG standard cloud models to determine if the current user can use this mobile device. This authentication method was evaluated from three aspects including accuracy, authentication time and energy consumption. The proposed method gives 86.04% of true acceptance rate with 2.73% of false acceptance rate. One authentication can be done in 6s, and this processing consumes about 2000 mW of power. PMID- 27681009 TI - "Housing First" for Homeless Youth With Mental Illness. AB - BACKGROUND AND OBJECTIVES: "Housing First" has been shown to improve housing stability in homeless individuals with mental illness, but had not been empirically tested in homeless youth. We aimed to evaluate the effect of "Housing First" on housing stability in homeless youth aged 18 to 24 years participating in At Home/Chez Soi, a 24-month randomized trial of "Housing First" in 5 Canadian cities. METHODS: Homeless individuals with mental illness were randomized to receive "Housing First" (combined with assertive community treatment or intensive case management depending on their level of need) or treatment as usual. We defined our primary outcome, housing stability, as the percent of days stably housed as a proportion of days for which residence data were available. RESULTS: Of 2148 participants who completed baseline interviews and were randomized, 7% (n = 156) were youth aged 18 to 24 years; 87 received "Housing First" and 69 received treatment as usual. In an adjusted analysis, youth in "Housing First" were stably housed a mean of 437 of 645 (65%) days for which data were available compared with youth in treatment as usual, who were stably housed a mean of 189 of 582 (31%) days for which data were available, resulting in an adjusted mean difference of 34% (95% confidence interval, 24%-45%; P < .001). CONCLUSIONS: "Housing First" was associated with improved housing stability in homeless youth with mental illness. Future research should explore whether adaptations of the model for youth yield additional improvements in housing stability and other outcomes. PMID- 27681010 TI - Preterm Thrombocytopenia and Delay of Ductus Arteriosus Closure. AB - OBJECTIVES: To evaluate whether preterm thrombocytopenia within 24 hours of birth is associated with delayed closure of patent ductus arteriosus (PDA) and higher proportion of hemodynamically significant PDA (Hs-PDA). METHODS: Neonates (gestation 260/7-336/7 weeks, age <24 hours) with known platelet count and PDA on echocardiogram were prospectively enrolled. Asphyxia, congenital infections, structural heart disease, major malformations and clinical sepsis were exclusions. Subjects were recruited in groups A (n = 35), B (n = 18), and C (n = 17) [platelet counts >150,000, 100,000-150,000 and <100,000 per MUL respectively] and underwent daily echocardiography until first closure of PDA, death, or day 10. RESULTS: The primary outcome was time to first closure of PDA. Secondary outcomes included proportion with PDA at 72 hours and 7 days, Hs-PDA, and PDA needing treatment. In groups A, B, and C, median (first-third quartile) platelet counts (*100000/MUL) were 2.28 (1.94-3.19), 1.25 (1.14-1.37), and 0.68 (0.54 0.83) and time to PDA closure was 2 (2-2), 2 (2-3), and 10 (6-10) days, respectively (log-rank test, P < .001). On Cox proportional hazard regression, platelet count (in multiples of 10 000 /MUL) independently predicted time to PDA closure (adjusted hazard ratio: 1.045; 95% confidence interval: 1.019-1.07). On day 7, 47.1% neonates in group C had PDA and none in groups A and B (P < .001). CONCLUSIONS: Thrombocytopenia within 24 hours of birth independently predicts delayed PDA closure and PDA on day 7 in preterm neonates. PMID- 27681011 TI - Efficacy and Safety of Rivaroxaban and Warfarin in the Perioperative Period of Catheter Ablation for Atrial Fibrillation - Outcome Analysis From a Prospective Multicenter Registry Study in Japan. AB - BACKGROUND: Catheter ablation (CA) is a common treatment for atrial fibrillation (AF). Although rivaroxaban is increasingly used as a substitute for warfarin, its safety and efficacy during CA have not been established in Japanese patients. In the present study we explored the efficacy/safety of rivaroxaban during the CA perioperative period.Methods and Results:We prospectively enrolled Japanese AF patients scheduled for CA who had received either rivaroxaban (rivaroxaban cohort, JACRE-R) or warfarin (warfarin cohort, JACRE-W) during the perioperative period. Primary outcome was a composite of thromboembolism and major bleeding within 30 days after CA. In JACRE-R and JACRE-W, 1,118 (median age, 65 years) and 204 patients (median, 69 years) were enrolled from 42 and 22 institutions, respectively. In JACRE-R, the primary outcome occurred in 7 patients (0.6%), comprising thromboembolism in 2 and major bleeding in 5. Non-major bleeding occurred in 27 patients (2.4%), and the incidence was significantly lower in patients without heparin bridging (n=572) than in those with heparin bridging (n=546). In JACRE-W, the primary outcome occurred in 3 patients (1.5%), all of which were major bleeding. After adjustment for patients' characteristics, no significant difference was observed between the JACRE-R and JACRE-W cohorts for the primary outcome. CONCLUSIONS: The rates of thromboembolism and major bleeding events during the AF ablation perioperative period in Japanese patients treated with rivaroxaban was as low as in those treated with warfarin. (Circ J 2016; 80: 2295-2301). PMID- 27681012 TI - Invisible Scars: Comparing the Mental Health of LGB and Heterosexual Intimate Partner Violence Survivors. AB - Intimate partner violence (IPV) affects countless women and men in lesbian, gay, and bisexual (LGB) as well as heterosexual relationships, but few studies have examined how such abuse is associated with the mental health of LGB victims. The present study addresses this issue using data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS) survey to examine differences in depression and anxiety among IPV victims in LGB and heterosexual partnerships. The findings indicate LGB IPV victims are much more likely to have a history of depression (OR 1.70, p < .05) and anxiety (OR 1.70, p < .05) than heterosexual victims. These differences are slightly mediated by the victim's perceived emotional support but not the type of abuse experienced. Our findings accentuate the need for greater inclusion of LGB persons in the IPV and mental health discourse, as well as the importance of social support for IPV victims. Policy implications for members of the LGB community are discussed. PMID- 27681013 TI - Erratum: Survival trade-offs in plant roots during colonization by closely related beneficial and pathogenic fungi. PMID- 27681014 TI - Synthesis of Some Novel 2-Substitutedbenzyl-(4)7-phenyl-1H-benzo[d]imidazoles in Mild Conditions as Potent Anti-Tyrosinase and Antioxidant Agents. AB - Novel 2-substitutedbenzyl-4(7)-phenyl-1H-benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC50 values ranging from 37.86 +/- 0.24 to 75.81 +/- 2.49 MUM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC50 = 37.86 +/- 0.24 uM) to the positive control, kojic acid (IC50 = 21.93 +/- 0.11 uM). Kinetic studies revealed it to act as non competitive tyrosinase inhibitor with a Ki value of 50.2 uM. The antioxidant activities of the compounds were investigated by using in vitro antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). All of these results indicated that the compounds might have potential application as tyrosinase inhibitors. PMID- 27681015 TI - Metabolic profile and safety of piperlongumine. AB - Piperlongumine (PPL), a natural plant product, has been extensively studied in cancer treatment going up on clinical trials. Since the first report related to its use on cancer research (in 2011) around 80 papers have been published in less than 10 years, but a gap still remaining. There are no metabolism studies of PPL in human organism. For the lack of a better view, here, the CYP450 in vitro oxidation of PPL was described for the first time. In addition, the enzymatic kinetic data, the predicted in vivo parameters, the produced metabolites, the phenotyping study and possible piperlongumine-drug interactions in vivo is presented. PMID- 27681016 TI - Efficacy of interdental calibrated brushes on bleeding reduction in adults: a 3 month randomized controlled clinical trial. AB - This study investigated the effect of interdental brushes on the reduction of interproximal bleeding in adults without periodontal disease. Forty-six adults were enrolled in a 3-month, observer-blinded, parallel-group randomized control trial. The test group used a standard manual toothbrush twice daily and an interdental brush daily. The control group used a standard manual toothbrush. At each visit, a calibrated colorimetric probe was used in all interdental spaces to determine the appropriate size of the interdental brush required, the brush of the corresponding size was introduced into the interproximal space, and the presence of bleeding was recorded. The outcome was the frequency of bleeding after application of the appropriate interdental brush. All participants were evaluated 1 wk, 1 month, and 3 months after the baseline visit. The overall preventive fraction with respect to bleeding frequency was 46% at 1 wk and 72% at 3 months. More bleeding reduction was observed in anterior sites than in posterior sites (80% vs. 69%, respectively). Participants with low baseline bleeding frequency presented with less bleeding (OR = 2.3). This study shows that daily use of calibrated interdental brushes reduces interdental bleeding. These findings may support interdental cleaning as an effective means to help individuals maintain and/or achieve optimal oral health. PMID- 27681017 TI - Study of the liquid-film-forming apparatus as an alternative aeration system: design criteria and operating condition. AB - Aeration is an important factor in aquaculture systems because it is a vital condition for all organisms that live in water and respire aerobically. Generally, mechanical surface aerators are widely used in Thailand due to their advantage for increasing dissolved oxygen (DO) and for their horizontal mixing of aquaculture ponds with large surface areas. However, these systems still have some drawbacks, primarily the low oxygen transfer efficiency (OTE) and energy. Regarding this issue, alternative aeration systems should be studied and applied. Therefore, this research aims to study the aeration mechanism obtained by the diffused-air aeration combined with a liquid-film-forming apparatus (LFFA). The effect of gas flow rates, types, and patterns of aerator installation were investigated in an aquaculture pond of 10 m * 10 m * 1.5 m. The analytical parameters were volumetric mass transfer coefficient (kLa), OTE, and aeration efficiency (AE). From the results, the '4-D' with partitions was proposed as the suitable pattern for the LFFA installation. The advantage could be obtained from high energy performance with 1.2 kg/kW h of AE. Then, the operation conditions can be applied as a design guideline for this alternative aeration system in the aquaculture ponds. PMID- 27681018 TI - Rethinking gossip and scandal in healthcare organizations. AB - Purpose The purpose of this paper is to argue that gossip is a neglected aspect of organizational communication and knowledge, and an under-used management resource. Design/methodology/approach The paper challenges mainstream managerial assumptions that gossip is trivial or tainted talk which should be discouraged in the workplace. Instead, gossip is re-framed at an organizational level of analysis, which provides the opportunity for relational knowledge about systemic failure and poor practice in healthcare to surface. Findings Rather than simply viewing gossip as an individual behaviour and interpersonal process, it is claimed that organizational gossip is also a valuable early warning indicator of risk and failure in healthcare systems. There is potentially significant value in re-framing gossip as an aspect of organizational communication and knowledge. If attended to (rather than neglected or silenced) gossip can provide fresh insights into professional practice, decision making and relational leadership. Originality/value This paper offers a provocative challenge to mainstream health organization and management thinking about gossip in the workplace. It offers new ways of thinking to promote patient safety, and prevent the scandals that have plagued healthcare organizations in recent years. PMID- 27681019 TI - Implementation of the affordable care act: a case study of a service line co management company. AB - Purpose The purpose of this paper is to test and measure the outcome of a community hospital in implementing the Affordable Care Act (ACA) through a co management arrangement. RQ1: do the benefits of a co-management arrangement outweigh the costs? RQ2: does physician alignment aid in the effective implementation of the ACA directives set for hospitals? Design/methodology/approach A case study of a 350-bed non-profit community hospital co-management company. The quantitative data are eight quarters of quality metrics prior and eight quarters post establishment of the co-management company. The quality metrics are all based on standardized national requirements from the Joint Commission and Centers for Medicare and Medicaid Services guidelines. These measures directly impact the quality initiatives under the ACA that are applicable to all healthcare facilities. Qualitative data include survey results from hospital employees of the perceived effectiveness of the co management company. A paired samples difference of means t-test was conducted to compare the timeframe before co-management and post co-management. Findings The findings indicate that the benefits of a co-management arrangement do outweigh the costs for both the physicians and the hospital ( RQ1). The physicians benefit through actual dollar payout, but also with improved communication and greater input in running the service line. The hospital benefits from reduced cost - or reduced penalties under the ACA - as well as better communication and greater physician involvement in administration of the service line. RQ2: does physician alignment aid in the effective implementation of the ACA directives set for hospitals? The hospital improved in every quality metric under the co-management company. A paired sample difference of means t-test showed a statistically significant improvement in five of the six quality metrics in the study. Originality/value Previous research indicates the potential effectiveness of co management companies in improving healthcare delivery and hospital-physician relations (Sowers et al., 2013). The current research takes this a step further to show that the data do in fact support these concepts. The hospital and the physicians carrying out the day-to-day actions have shared goals, better communication, and improved quality metrics under the co-management company. As the number of co-management companies increases across the USA, more research can be directed at determining their overall impact on quality care. PMID- 27681020 TI - The performance of primary health care organizations depends on interdependences with the local environment. AB - Purpose Improving the performance of health care organizations is now perceived as essential in order to better address the needs of the populations and respect their ability to pay for the services. There is no consensus on what is performance. It is increasingly considered as the optimal execution of four functions that every organization must achieve in order to survive and develop: reach goals; adapt to its environment; produce goods or services and maintain values; and a satisfying organizational climate. There is also no consensus on strategies to improve this performance. The paper aims to discuss these issues. Design/methodology/approach This paper intends to analyze the performance of primary health care organizations from the perspective of Kauffman's model. It mainly aims to understand the often contradictory, paradoxical and unexpected results that emerge from studies on this topic. Findings To do so, the first section briefly presents Kauffman's model and lays forward its principal components. The second section presents three studies on the performance of primary organizations and brings out the contradictory, paradoxical and unexpected results they obtained. The third section explains these results in the light of Kauffman's model. Originality/value Kauffman's model helps give meaning to the results of researches on performance of primary health care organizations that were qualified as paradoxical or unexpected. The performance of primary health care organizations then cannot be understood by only taking into account the characteristics of these organizations. The complexity of the environments in which they operate must simultaneously be taken into account. This paper brings original development of an integrated view of the performance of organizations, their own characteristics and those of the local environment in which they operated. PMID- 27681021 TI - Interorganizational collaboration in public health data sharing. AB - Purpose The purpose of this paper is to analyze the institutional and social forces that influence collaborative data sharing practices in cross-sector interorganizational networks. The analysis focusses on the data sharing practices between professionals in the transportation and public health sectors, areas prioritized for collaborative action to improve public health. Design/methodology/approach A mixed methods design is utilized. Electronic surveys were sent to 57 public health and 157 transportation professionals in a large major metropolitan area in the USA (response rate 39.7 percent). Focus groups were held with 12 organizational leaders representing professionals in both sectors. Findings The application of the institutional-social capital framework suggests that professional specialization and organizational forces make it challenging for professionals to develop the cross-sector relationships necessary for cross-sector collaborative data sharing. Research limitations/implications The findings suggest that developing the social relationships necessary for cross-sector collaboration may be resource intensive. Investments are necessary at the organizational level to overcome the professional divides that limit the development of cross-sector relationships critical for collaborative data sharing. The results are limited to the data sharing practices of professionals in one metropolitan area. Originality/value Despite mandates and calls for increased cross-sector collaboration to improve public health, such efforts often fail to produce true collaboration. The study's value is that it adds to the theoretical conceptualization of collaboration and provides a deeper understanding as to why collaborative action remains difficult to achieve. Future study of collaboration must consider the interaction between professional specialization and the social relationships necessary for success. PMID- 27681022 TI - What factors determine the choice of public engagement undertaken by health technology assessment decision-making organizations? AB - Purpose Public engagement in health technology assessment (HTA) is increasingly considered crucial for good decision making. Determining the "right" type of engagement activity is key in achieving the appropriate consideration of public values. Little is known about the factors that determine how HTA organizations (HTAOs) decide on their method of public engagement, and there are a number of possible factors that might shape these decisions. The purpose of this paper is to understand the potential drivers of public engagement from an organizational perspective. Design/methodology/approach The published HTA literature is reviewed alongside existing frameworks of public engagement in order to elucidate key factors influencing the choice of public engagement process undertaken by HTAOs. A conceptual framework is then developed to illustrate the factors identified from the literature that appear to influence public engagement choice. Findings Determining the type of public engagement undertaken in HTA is based on multiple factors, some of which are not always explicitly acknowledged. These factors included the: perceived complexity of the policy-making issue, perceived impact of the decision, transparency and opportunities for public involvement in governance, as well as time and resource constraints. The influences of these factors vary depending on the context, indicating that a one size fits all approach to public engagement may not be effective. Originality/value Awareness of the various factors that might influence the type of public engagement undertaken would enable decision makers to reflect on their choices and be more accountable and transparent about their choice of engagement process in eliciting public values and preferences in a HTAO. PMID- 27681023 TI - Formal priority setting in health care: the Swedish experience. AB - Purpose From the late 1980s and onwards health care in Sweden has come under increasing financial pressure, forcing policy makers to consider restrictions. The purpose of this paper is to review experiences and to establish lessons of formal priority setting in four Swedish regional health authorities during the period 2003-2012. Design/methodology/approach This paper draws on a variety of sources, and evidence is organised according to three broad aspects: design and implementation of models and processes, application of evidence and decision analysis tools and decision making and implementation of decisions. Findings The processes accounted for here have resulted in useful experiences concerning technical arrangements as well as political and public strategies. All four sites used a particular model for priority setting that combined top-down- and bottom up-driven elements. Although the process was authorised from the top it was clearly bottom-up driven and the template followed a professional rationale. New meeting grounds were introduced between politicians and clinical leaders. Overall a limited group of stakeholders were involved. By defusing political conflicts the likelihood that clinical leaders would regard this undertaking as important increased. Originality/value One tendency today is to unburden regional authorities of the hard decisions by introducing arrangements at national level. This study suggests that regional health authorities, in spite of being politically governed organisations, have the potential to execute a formal priority-setting process. Still, to make priority-setting processes more robust to internal as well as external threat remains a challenge. PMID- 27681024 TI - Measuring distributed leadership agency in a hospital context. AB - Purpose The purpose of this paper is to develop and validate an instrument that can measure distributed leadership (DL) as employees' active participation in DL tasks. The authors designate this as the distributed leadership agency (DLA). Design/methodology/approach Data were collected throughout all departments and occupational groups at a merged centralized hospital setting in Denmark. A total of 1,774 employees from 24 hospital departments and 16 occupational groups completed our survey. Structural equation model and confirmatory factor analyses were applied to identify appropriate items and a test for measurement invariance, predictive, discriminant and convergent validity, and ANOVAs were applied to analyse group differences in DLA. Findings The identified unidimensional questionnaire consists of seven items, as it is different from, but associated with, empowering leadership, organizational influence, attitude to participation and trust in management. As theoretically predicted, DLA is positively related to self-efficacy, job satisfaction and innovative behaviour. Chief physicians, permanent employees and employee representatives scored higher on the scale than the rest of their respective counterparts. Practical implications The survey offers a method to assess a distribution of leadership agency in hospital organizations. Such assessment may provide a basis for organizational and leadership development. Originality/value The present study provides a reliable and valid quantitative instrument that measures how much employees at all hierarchical levels are involved in concrete leadership activities in the hospital context. Taking a normative perspective the authors could show that DL - measured with the DLA-questionnaire - has positive effects on employees' behaviour. PMID- 27681025 TI - Alignment of governance and senior executive perceptions of culture. AB - Purpose The purpose of this paper is to examine the alignment of perceived organizational culture between Health Board chairs and Board members with that of their respective senior executive teams. It compares the degree of alignment between these two groups, and analyses them against District Health Board (DHB) performance using the New Zealand Ministry of Health's national measure "shorter stays in Emergency Departments." Design/methodology/approach Primary survey data were collected across eight DHBs using a modified version of the Organizational Culture Assessment Instrument and utilizes a sample of both higher and lower performing DHBs as defined by the "shorter stays" measure. Findings Many health organizations cite Ovseiko and Buchan's (2012) preferred culture as an ideal model. However, this study's findings indicate that most DHBs scored higher than the preferred score for "Hierarchical" and "Rational" cultures, and lower for "Clan" and "Developmental" cultures, and therefore calls into question the validity of this organizational profile as the "preferred" cultural state. Research limitations/implications This research considers perceived organizational culture from the perspective of the Board members and their respective senior executive teams. It uses a relatively small sample size and excludes potential interactions of national culture. Practical implications The findings indicate that healthcare organizations should de-emphasize the dominant "Hierarchical" and "Rational" cultures, and promote "Clan" and "Developmental" cultures within their organizations as a means of potentially improving healthcare performance. Originality/value Organizational culture has been highlighted as a major component of performance within healthcare organizations, yet very few studies examine how organizational culture is perceived by governance and executive groups. This study empirically counters prevailing knowledge regarding the most appropriate organizational cultures for healthcare organizations. PMID- 27681026 TI - Process redesign for time-based emergency admission targets. AB - Purpose Hospitals have used process redesign to increase the efficiency of the emergency department (ED) to cope with increasing demand. While there are published studies suggesting a positive outcome, recent reviews have reported that it is difficult to conclude that these approaches are effective as a result of substandard research methodology. The purpose of this paper is to explore the perceptions of hospital staff on the impact of a process redesign initiative on quality of care. Design/methodology/approach A retrospective qualitative case study examining a Lean Six Sigma (LSS) initiative in a large metropolitan hospital from 2009 to 2010. Non-probability sampling identified interview subjects who, through their participation in the redesign initiative, had a detailed understanding of the implementation and outcomes of the initiative. Between April 2012 and January 2013 26 in-depth semi-structured interviews were conducted and analysed with thematic content analysis. Findings There were four important findings. First, when asked to comment on the impact of the LSS implementation, without prompting the staff spoke of quality of care. Second, there was little agreement among the participants as to whether the project had been successful. Third, despite the recognition of the need for a coordinated effort across the hospital to improve ED access, the redesign process was not successful in reducing existing divides among clinicians and among managers and clinicians. Finally, staff expressed tension between production processes to move patients more quickly and their duty of care to their patients as individuals. Originality/value One of the first studies to explore the impact of process redesign through in-depth interviews with participating staff, this study adds further evidence that organisations implementing process redesign must ensure the supporting management practices are in place. PMID- 27681027 TI - Developing an evaluation framework for clinical redesign programs: lessons learnt. AB - Purpose The purpose of this paper is to present lessons learnt through the development of an evaluation framework for a clinical redesign programme - the aim of which was to improve the patient journey through improved discharge practices within an Australian public hospital. Design/methodology/approach The development of the evaluation framework involved three stages - namely, the analysis of secondary data relating to the discharge planning pathway; the analysis of primary data including field-notes and interview transcripts on hospital processes; and the triangulation of these data sets to devise the framework. The evaluation framework ensured that resource use, process management, patient satisfaction, and staff well-being and productivity were each connected with measures, targets, and the aim of clinical redesign programme. Findings The application of business process management and a balanced scorecard enabled a different way of framing the evaluation, ensuring measurable outcomes were connected to inputs and outputs. Lessons learnt include: first, the importance of mixed-methods research to devise the framework and evaluate the redesigned processes; second, the need for appropriate tools and resources to adequately capture change across the different domains of the redesign programme; and third, the value of developing and applying an evaluative framework progressively. Research limitations/implications The evaluation framework is limited by its retrospective application to a clinical process redesign programme. Originality/value This research supports benchmarking with national and international practices in relation to best practice healthcare redesign processes. Additionally, it provides a theoretical contribution on evaluating health services improvement and redesign initiatives. PMID- 27681028 TI - Grassroots inter-professional networks: the case of organizing care for older cancer patients. AB - Purpose The purpose of this paper of inter-professional networks is to analyze the evolution of relationships between professional groups enacting new forms of collaboration to address clinical imperatives. Design/methodology/approach This paper uses a case study based on semi-structured interviews with physicians and nurses, document analysis and informal discussions. Findings This study documents how two inter-professional networks were developed through professional agency. The findings show that the means by which networks are developed influence the form of collaboration therein. One of the networks developed from day-to-day, immediately relevant, exchange, for patient care. The other one developed from more formal and infrequent research and training exchanges that were seen as less decisive in facilitating patient care. The latter resulted in a loosely knit network based on a small number of ad hoc referrals while the other resulted in a tightly knit network based on frequent referrals and advice seeking. Practical implications Developing inter-professional networks likely require a sustained phase of interpersonal contacts characterized by persuasion, knowledge sharing, skill demonstration and trust building from less powerful professional groups to obtain buy-in from more powerful professional groups. The nature of the collaboration in any resulting network depends largely on the nature of these initial contacts. Originality/value The literature on inter-professional healthcare networks focusses on mandated networks such as NHS managed care networks. There is a lack of research on inter-professional networks that emerged from the bottom up at the initiative of healthcare professionals in response to clinical imperatives. This study looks at some forms of collaboration that these "grass-root" initiatives engender and how they are consolidated. PMID- 27681029 TI - Key success factors behind electronic medical record adoption in Thailand. AB - Purpose The purpose of this paper is to investigate the elements that health care personnel in Thailand believe are necessary for successful adoption of electronic medical record (EMR) systems. Design/methodology/approach Initial qualitative in depth interviews with physicians to adapt key elements from the literature to the Thai context. The 12 elements identified included things related to managing the implementation and to IT expertise. The nationwide survey was supported by the Ministry of Public Health and returned 1,069 usable questionnaires (response rate 42 percent) from a range of medical personnel. Findings The key elements clearly separated into a managerial dimension and an IT dimension. All were considered fairly important, but managerial expertise was more critical. In particular, there should be clear EMR project goals and scope, adequate budget allocation, clinical staff must be involved in implementation, and the IT should facilitate good electronic communication. Research limitations/implications Thailand is representative of middle-income developing countries, but there is no guarantee findings can be generalized. National policies differ, as do economic structures of health care industries. The focus is on management at the organizational level, but future research must also examine macro-level issues, as well as gain more depth into thinking of individual health care personnel. Practical implications Technical issues of EMR implementation are certainly important. However, it is clear actual adoption and use of the system also depends very heavily on managerial issues. Originality/value Most research on EMR implementation has been in developed countries, and has often focussed more on technical issues rather than examining managerial issues closely. Health IT is also critical in developing economies, and management of health IT implementation must be well understood. PMID- 27681030 TI - Comparing the implementation consequences of the immunisation and emergency department health targets in New Zealand. AB - Purpose Over the last decade there has been considerable debate about the merits of targets as a policy instrument. The purpose of this paper is to examine the implementation of two health targets that were cornerstones of New Zealand health policy between 2009 and 2012: immunisation rates for two-year-olds, and time to treatment, discharge or admission in hospital emergency departments. Design/methodology/approach For each policy target, the authors selected four case-study districts and conducted two waves of key-informant interviews (113 in total) with clinical and management staff involved in target implementation. Findings Despite almost identical levels of target achievement, the research reveals quite different mixes of positive and negative implementation consequences. The authors argue that the differences in implementation consequences are due to the characteristics of the performance measure; and the dynamics of the intra-organisational and inter-organisational implementation context. Research limitations/implications The research is based on interviews with clinical and management staff involved in target implementation, and this approach does not address the issue of effort substitution. Practical implications While literature on health targets pays attention to the attributes of target measures, the paper suggests that policymakers considering the use of targets pay more attention to broader implementation contexts, including the possible impact of, and effects on related services, organisations and staff. Originality/value The research focuses specifically on implementation consequences, as distinct from target success and/or changes in clinical and health outcomes. The paper also adopts a comparative approach to the study of target implementation. PMID- 27681032 TI - Effects of Extraction and Purification Methods on Degradation Kinetics and Stability of Lycopene from Watermelon under Storage Conditions. AB - Lycopene was extraction, isolation and purification using recrystallization, column chromatography, and preparative thin layer chromatography (TLC) methods as well as degradation kinetics of lycopene were studied at refrigerated temperature and room temperature for 3 wk from watermelon. Higher lycopene degradation was observed at refrigerated temperature as compared to ambient temperature throughout the storage periods. The highest amount of lycopene retained in recrystallization (101.69 MUg/g) followed by column chromatography (18.20 MUg/g) and preparative TLC (15.57 MUg/g). Color parameters, half-life time (t1/2 ), and color retention (%R) were dependent on extraction, isolation, and purification methods and storage life. Recrystallization and preparative TLC were followed by first order reaction model. Preparative TLC exhibited higher activation energy than did the recrystallization and column chromatography. Therefore, the result shows that recrystallization method could apply to extract and purify lycopene from watermelon that would also be used as a natural colorant as well as value added product. PMID- 27681031 TI - Acidic Residues Control the Dimerization of the N-terminal Domain of Black Widow Spiders' Major Ampullate Spidroin 1. AB - Dragline silk is the most prominent amongst spider silks and comprises two types of major ampullate spidroins (MaSp) differing in their proline content. In the natural spinning process, the conversion of soluble MaSp into a tough fiber is, amongst other factors, triggered by dimerization and conformational switching of their helical amino-terminal domains (NRN). Both processes are induced by protonation of acidic residues upon acidification along the spinning duct. Here, the structure and monomer-dimer-equilibrium of the domain NRN1 of Latrodectus hesperus MaSp1 and variants thereof have been investigated, and the key residues for both could be identified. Changes in ionic composition and strength within the spinning duct enable electrostatic interactions between the acidic and basic pole of two monomers which prearrange into an antiparallel dimer. Upon naturally occurring acidification this dimer is stabilized by protonation of residue E114. A conformational change is independently triggered by protonation of clustered acidic residues (D39, E76, E81). Such step-by-step mechanism allows a controlled spidroin assembly in a pH- and salt sensitive manner, preventing premature aggregation of spider silk proteins in the gland and at the same time ensuring fast and efficient dimer formation and stabilization on demand in the spinning duct. PMID- 27681033 TI - A real-time approach for heart rate monitoring using a Hilbert transform in seismocardiograms. AB - Heart rate monitoring helps in assessing the functionality and condition of the cardiovascular system. We present a new real-time applicable approach for estimating beat-to-beat time intervals and heart rate in seismocardiograms acquired from a tri-axial microelectromechanical accelerometer. Seismocardiography (SCG) is a non-invasive method for heart monitoring which measures the mechanical activity of the heart. Measuring true beat-to-beat time intervals from SCG could be used for monitoring of the heart rhythm, for heart rate variability analysis and for many other clinical applications. In this paper we present the Hilbert adaptive beat identification technique for the detection of heartbeat timings and inter-beat time intervals in SCG from healthy volunteers in three different positions, i.e. supine, left and right recumbent. Our method is electrocardiogram (ECG) independent, as it does not require any ECG fiducial points to estimate the beat-to-beat intervals. The performance of the algorithm was tested against standard ECG measurements. The average true positive rate, positive prediction value and detection error rate for the different positions were, respectively, supine (95.8%, 96.0% and ?0.6%), left (99.3%, 98.8% and ?0.001%) and right (99.53%, 99.3% and ?0.01%). High correlation and agreement was observed between SCG and ECG inter-beat intervals (r > 0.99) for all positions, which highlights the capability of the algorithm for SCG heart monitoring from different positions. Additionally, we demonstrate the applicability of the proposed method in smartphone based SCG. In conclusion, the proposed algorithm can be used for real-time continuous unobtrusive cardiac monitoring, smartphone cardiography, and in wearable devices aimed at health and well-being applications. PMID- 27681034 TI - Effectiveness of Prolonged Exposure and Cognitive Processing Therapy for U.S. Veterans With a History of Traumatic Brain Injury. AB - This retrospective analysis of previously existing nonrandomized clinical data examined the effectiveness of completing prolonged exposure (PE) or cognitive processing therapy (CPT) in a sample of 41 U.S. veterans at a Veterans Affairs medical center. The sample included 19 veterans with diagnoses of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and 22 veterans with PTSD only. Diagnostic groups did not significantly differ on PTSD and depression symptom reduction, F(2, 36) = 0.05, p = .951; Pillai's trace = 0.00, partial eta2 = .00. Veterans who completed PE showed greater symptom reduction than those who completed CPT, F(2, 36) = 12.10, p < .001; Pillai's trace = 0.40, partial eta2 = .40, regardless of TBI status. Overall, our results suggested that TBI status should not preclude individuals from being offered trauma-focused PTSD treatment. PMID- 27681035 TI - Aortic valve repair in the paediatric population: insights from a 38-year single centre experience. AB - OBJECTIVES: To analyse our institutional results in the setting of paediatric aortic valve (AV) repair. Primary end-points were overall survival, freedom from AV reoperation and freedom from AV replacement. METHODS: A retrospective analysis of all patients under 18 years of age operated on from 1977 to 2015 in a single tertiary care level institution. Patients were included if they benefited from any type of AV repair procedure, including commissurotomy, leaflet shaving or plication, or leaflet augmentation. All data were gathered from patients' medical records, operative reports and referring paediatric cardiologists. The median follow-up was 50 months (IQR [13-140]). RESULTS: Sixty-six patients were included. Indications for surgery were aortic stenosis, aortic regurgitation and mixed disease in 13 (19%), 36 (55%) and 17 (26%) patients, respectively. According to El Khoury's functional classification, among the 55 patients with some degree of regurgitation there were 5 type Ib regurgitation, 23 type II and 27 type III. During AV repair, additional procedures were performed in 36 patients, VSD closure, subaortic membrane resection and mitral valve repair being the most frequent (18, 8 and 7 patients). RACHS score was predominantly 2 (98.5% of patients). The in-hospital mortality rate was 1.5% (1/66). Major morbidity included 10 pericardial effusions (1 pericardocentesis), 1 low cardiac output syndrome and 1 stroke. There were three late deaths (at 104, 140 and 179 months after repair). All were cardiac related. Overall 5- and 10-year survival rates were 100 and 95.7%. The rates of freedom from AV reoperation and AV replacement at 5 and 10 years were 90.6, 72.1 and 92.5, 82.7%, respectively. During follow up, there was no occurrence of valve-related complication (endocarditis, thromboembolism and bleeding). CONCLUSIONS: In our experience, AV repair in the paediatric population provides excellent results in terms of both overall survival and valve-related reoperation. It obviates the need for chronic anticoagulation and in most cases delays the time at which more complex surgery such as the Ross procedure should be undertaken. PMID- 27681036 TI - Drill-related root injury caused by intraoperative intermaxillary fixation: an analysis of 1067 screw applications. AB - BACKGROUND/AIMS: Intermaxillary fixation is a standard procedure for the treatment of mandibular fractures or in orthognathic surgery. Predrilling for screws poses the risk of accidental tooth root injury, potentially leading to further pathological processes. Limited evidence about accidental tooth injury during intermaxillary fixation is available due to heterogenous study designs. The aim of this study was to evaluate the risk of root trauma using predrilled transgingival fixation screws and the clinical consequences for the affected teeth. MATERIALS AND METHODS: In this retrospective study, the data of open reduction and internal fixation surgery files with intraoperative application of predrilled intermaxillary fixation screws were analysed. The postoperative radiographic images were evaluated for the occurrence of tooth root injury. Patients diagnosed with root injury were clinically followed up with respect to the dental health for the affected teeth. RESULTS: A total of 133 radiologically diagnosed tooth root injuries were recorded (12.5% of screws). The median follow up interval was 16 months (range: 3-77 months). The return rate was 49.5% for all patients. Of these, four of the injured teeth (3%) needed endodontic treatment. No toothache was reported, no tooth was lost, and no negative impact on periodontal health was clinically evident. CONCLUSION: Intermaxillary fixation with predrilled transgingival screws is a safe way to manage mandibular fractures. The incidence of tooth root injury is not uncommon, but the adverse side effects are rare and the health of the affected teeth is mostly not compromised. PMID- 27681037 TI - Organizational Health Interventions: Advances in Evaluation Methodology. PMID- 27681038 TI - High-Resolution Identification of Specificity Determining Positions in the LacI Protein Family Using Ensembles of Sub-Sampled Alignments. AB - Since the advent of large-scale genomic sequencing, and the consequent availability of large numbers of homologous protein sequences, there has been burgeoning development of methods for extracting functional information from multiple sequence alignments (MSAs). One type of analysis seeks to identify specificity determining positions (SDPs) based on the assumption that such positions are highly conserved within groups of sequences sharing functional specificity, but conserved to different amino acids in different specificity groups. This unsupervised approach to utilizing evolutionary information may elucidate mechanisms of specificity in protein-protein interactions, catalytic activity of enzymes, sensitivity to allosteric regulation, and other types of protein functionality. We present an analysis of SDPs in the LacI family of transcriptional regulators in which we 1) relax the constraint that all specificity groups must contribute to SDP signal, and 2) use a novel approach to robust treatment of sequence alignment uncertainty based on sub-sampling. We find that the vast majority of SDP signal occurs at positions with a conservation pattern that significantly complicates detection by previously described methods. This pattern, which we term "partial SDP", consists of the commonly accepted SDP conservation pattern among a subset of specificity groups and strong degeneracy among the rest. An upshot of this fact is that the SDP complement of every specificity group appears to be unique. Additionally, sub-sampling gives us the ability to assign a confidence interval to the SDP score, as well as increase fidelity, as compared to analysis of a single, comprehensive alignment-the current standard in multiple sequence alignment methodologies. PMID- 27681039 TI - Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms. AB - The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40-60 MUg/mL/40-100 MUg/mL), thymol (100-200 MUg/mL/200-400 MUg/mL), carvacrol (200-400 MUg/mL/200-600 MUg/mL), and menthol (500-more than 2500 MUg/mL/1000-more than 2500 MUg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80 degrees C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity. PMID- 27681041 TI - Motivational aftercare planning to better care: Applying the principles of advanced directives and motivational interviewing to discharge planning for people with mental illness. AB - Improving the input of people with mental illness into their recovery plans can potentially lead to better outcomes. In the present study, we evaluated the introduction of motivational aftercare planning (MAP) into the discharge planning of psychiatric inpatients. MAP is a manualized intervention combining motivational interviewing with advance directives. We measured changes in the level of patient input into discharge planning following training staff in the use of MAP. This included the following: (i) documentation of early relapse signs along with successful past responses; (ii) evidence of aftercare planning; and (iii) the use of the patients' own words in the plan. We used a ward-level controlled before-and-after design comparing one intervention ward with two control wards. We used anonymized recovery plans, with a goal of 50 plans per ward before and after the intervention, to look for evidence of patient input into care planning with a standardized checklist. There were also qualitative interviews with individuals discharged from the unit. We reviewed 100 intervention ward plans and 197 control ones (total n = 297). There were no significant differences in recovery plans from intervention and control wards at baseline. Following MAP training, the intervention ward improved significantly (e.g. identification of triggers increased from 52 to 94%, chi2 = 23.3, d.f. =1, P < 0.001). This did not occur in the control wards. The qualitative data (n = 20 interviews) showed improvements in participants' experiences of discharge planning. MAP increased inpatient input into discharge planning and was valued by participants. The effect on subsequent health service use needs evaluation. PMID- 27681040 TI - Miltefosine Suppresses Hepatic Steatosis by Activating AMPK Signal Pathway. AB - BACKGROUND AND PURPOSE: It has been accepted that AMPK (Adenosine monophosphate activated protein kinase) activation exhibits many beneficial effects on glucolipid metabolism. Lysophosphatidylcholine (LPC) is an important lysophospholipid which can improve blood glucose levels in diabetic mice and attenuate inflammation by activating AMPK signal pathway in macrophages. Synthetic alkylphospholipids (ALPs), such as miltefosine, is used as an alternate of LPC for the clinical application. Here, we investigated whether miltefosine could have an impact on hepatic steatosis and related metabolic disorders. EXPERIMENTAL APPROACH: Mice were fed with high fat diet (HFD) for 16 weeks to generate an obese model. Next, the obese mice were randomly divided into three groups: saline-treated and miltefosine-treated (2.5 or 5 mg/kg/d) groups. Miltefosine was intraperitoneally administrated into mice for additional 4 weeks plus HFD treatment. KEY RESULTS: It was shown that miltefosine treatment could substantially improve glucose metabolism, prevented hepatic lipid accumulation, and inhibited liver inflammation in HFD-fed mice by activating AMPK signal pathway. In vitro, miltefosine stimulated AMPKalpha phosphorylation both in time and dose dependent manner and decreased lipid accumulation in liver cells. When a specific AMPK inhibitor compound C was used to treat mice, the antagonistic effects of miltefosine on HFD-induced mouse hyperlipidaemia and liver steatosis were abolished. Treatment with miltefosine also dramatically inhibited the HFD induced liver inflammation in mice. CONCLUSIONS AND IMPLICATIONS: Here we demonstrated that miltefosine might be a new activator of AMPK signal pathway in vivo and in vitro and be useful for treatment of hepatic steatosis and related metabolic disorders. PMID- 27681042 TI - A qualitative study of collaboration in general practice: understanding the general practice nurse's role. AB - AIMS AND OBJECTIVES: To explore the nature of collaboration between registered nurses and general practitioners in Australian general practice. BACKGROUND: There is international recognition that collaboration between health professionals can improve care coordination, enhance health outcomes, optimise the work environment and reduce healthcare costs. However, effective collaboration requires a clear understanding of each team member's role. DESIGN: A qualitative approach guided by Naturalistic Inquiry was used to elicit and interpret participant narratives. METHODS: Eight general practitioners and fourteen registered nurses working in general practice were purposefully recruited. Data were collected via individual, semi-structured face-to-face interviews during February to May 2015. Interviews were audio recorded and transcribed verbatim. Data were analysed using thematic analysis. RESULTS: Data revealed three overarching themes. This study presents the data for the overarching theme 'Understanding the general practice registered nurse's role'. Many general practitioner participants lacked clarity around the role and scope of practice of the registered nurse. At the same time, nursing participants often articulated their role as an assistant rather than as an independent health professional. This limited collaboration and the nurses' role within the team. Collaboration was enhanced when general practitioners actively sought an understanding of the registered nurses scope of practice. CONCLUSION: Clarifying the nurses' role promotes collaboration and supports nurses to work to the full extent of their practice. This is important in terms of optimising the nurses' role within the team and reinforcing their professional identity. RELEVANCE TO CLINICAL PRACTICE: Identification of key issues around understanding the nurses' role may help inform strategies that improve collaboration and workplace relations. PMID- 27681043 TI - Localization of choline acetyltransferase and tyrosine hydroxylase immunoreactivities in the superior colliculus of the microbat, Rhinolophus ferrumequinum. AB - The purpose of this study was to determine whether the superior colliculus (SC) of the microbat has the same neurochemical makeup as that of other mammals. We examined the organization of choline acetyltransferase (ChAT)- and tyrosine hydroxylase-immunoreactive (TH-IR) fibers/cells using standard immunohistochemistry with antibodies against ChAT and TH. ChAT-IR fibers observed in the superficial layers were denser than those in the deeper layers, and these fibers were classified into two types: small varicose fibers and large varicose fibers. ChAT-IR cells were predominantly located in the superficial layers with diverse morphologies. Among the well-known sources of cholinergic fibers in the mammalian SC, pedunculopontine tegmental nucleus (PPTN) and laterodorsal tegmental nucleus (LDTN) contained strongly labeled ChAT-IR cells, while no cholinergic structures were found in the parabigeminal nucleus (PBG) in the microbat brain. TH-immunoreactivity was found within fibers but not within cells. The density of TH-IR fibers was high in the zonal layer, moderate in the superficial gray and optic layers, and low in the deeper layers. Well-labeled TH IR cells were also observed within area 13 and the locus coeruleus, known as the sources of catecholaminergic fibers in other mammalian SC. Although there are some cytoarchitectural variations among species, our results clearly showed elaborately organized ChAT-IR and TH-IR fibers/cells in the microbat SC. Our findings will contribute significantly to the understanding of actively constructed microbat visual systems. PMID- 27681045 TI - The dark universe. PMID- 27681046 TI - Dark matter: What's the matter? PMID- 27681044 TI - Functional expression of N-acetyltransferase 1 in differentiated human skin keratinocytes. PMID- 27681047 TI - Revealing the unseen Universe. PMID- 27681048 TI - Q&A: George Smoot. PMID- 27681050 TI - Q&A: Brian Schmidt. PMID- 27681051 TI - The dark universe: 4 big questions. PMID- 27681049 TI - Dark energy: Staring into darkness. PMID- 27681052 TI - Correlation between structural heterogeneity and plastic deformation for phase separating FeCu metallic glasses. AB - Unlike crystalline metals, the plastic deformation of metallic glasses (MGs) involves a competition between disordering and structural relaxation ordering, which is not well understood, yet. Molecular dynamics (MD) simulations were performed to investigate the evolutions of strain localizations, short-range order (SRO) as well as the free volume in the glass during compressive deformation of Fe50Cu50 MGs with different degrees of phase separation. Our findings indicate that the free volume in the phase separating MGs decreases while the shear strain localizations increase with increasing degree of phase separation. Cu-centered clusters show higher potential energies and Voronoi volumes, and bear larger local shear strains. On the other hand, Fe-centered pentagon-rich clusters in Cu-rich regions seem to play an important role to resist the shear transformation. The dilatation or annihilation of Voronoi volumes is due to the competition between ordering via structural relaxation and shear stress-induced deformation. The present study could provide a better understanding of the relationship between the structural inhomogeneity and the deformation of MGs. PMID- 27681054 TI - Revisiting Current Golden Rules in Managing Acute Ischemic Stroke: Evaluation of New Strategies to Further Improve Treatment Selection and Outcome. AB - OBJECTIVE: Advanced stroke imaging has generated much excitement for the early diagnosis of acute ischemic stroke (AIS) and facilitation of intervention. However, its therapeutic impact has not matched its diagnostic utility; most notably, lacking significant contributions to recent major AIS clinical trials. It is time to reexamine the fundamental hypotheses from the enormous body of imaging research on which clinical practices are based and reassess the current standard clinical and imaging strategies, or golden rules, established over decades for AIS. In this article, we will investigate a possible new window of opportunity in managing AIS through a better understanding of the following: first, the potential limitations of the golden rules; second, the significance of imaging-based parenchymal hypoperfusion (i.e., lower-than-normal relative cerebral blood flow [rCBF] may not be indicative of ischemia); third, the other critical factors (e.g., rCBF, collateral circulation, variable therapeutic window, chronicity of occlusion) that reflect more individual ischemic injury for optimal treatment selection; and, fourth, the need for penumbra validation in successfully reperfused patients (not in untreated patients). CONCLUSION: Individual variations in the therapeutic window, ischemic injury (rCBF), and chronicity of vascular lesion development have not been comprehensively incorporated in the standard algorithms used to manage AIS. The current established imaging parameters have not been consistently validated with successfully reperfused patients and rCBF to quantitatively distinguish between oligemia and ischemia and between penumbra and infarct core within ischemic tissue. A novel paradigm incorporating rCBF values or indirectly incorporating relative rCBF values with higher statistically powered imaging studies to more reliably assess the severity of ischemic injury and differentiate reversibility from viability within the area of imaging-based parenchymal hypoperfusion may provide a more personalized approach to treatment, including no treatment of infarction core, to further enhance outcomes. PMID- 27681053 TI - Climate forcing and infectious disease transmission in urban landscapes: integrating demographic and socioeconomic heterogeneity. AB - Urbanization and climate change are the two major environmental challenges of the 21st century. The dramatic expansion of cities around the world creates new conditions for the spread, surveillance, and control of infectious diseases. In particular, urban growth generates pronounced spatial heterogeneity within cities, which can modulate the effect of climate factors at local spatial scales in large urban environments. Importantly, the interaction between environmental forcing and socioeconomic heterogeneity at local scales remains an open area in infectious disease dynamics, especially for urban landscapes of the developing world. A quantitative and conceptual framework on urban health with a focus on infectious diseases would benefit from integrating aspects of climate forcing, population density, and level of wealth. In this paper, we review what is known about these drivers acting independently and jointly on urban infectious diseases; we then outline elements that are missing and would contribute to building such a framework. PMID- 27681056 TI - Visible-Light-Induced Cascade Reaction of Isocyanides and N-Arylacrylamides with Diphenylphosphine Oxide via Radical C-P and C-C Bond Formation. AB - An effective photoredox-mediated tandem phosphorylation/cyclization reaction of diphenylphosphine oxide with three types of radical acceptors leads to P(O)Ph2 containing phenanthridines, isoquinolines, and indolin-2-ones by formation of both C-P and C-C bonds. [Ir(ppy)2(dtbpy)]PF6 (1 mol %) was used as the catalyst, CsF or Cs2CO3 as the base, and K2S2O8 as the oxidant. A series of functional groups can be tolerated at room temperature. Moderate to good yields were generated. PMID- 27681055 TI - Polymorphism and Superconductivity in Bilayer Molecular Metals (CNB-EDT-TTF)4I3. AB - Electrocrystallization from solutions of the dissymmetrical ET derivative cyanobenzene-ethylenedithio-tetrathiafulvalene (CNB-EDT-TTF) in the presence of triiodide I3- affords two different polymorphs (beta" and kappa) with the composition (CNB-EDT-TTF)4I3, both with a bilayer structure of the donors. These polymorphs differ in the packing patterns (beta"- and kappa-type) of the donor molecules in each layer, in both cases with bifurcated C-N...H interactions effectively coupling head-to-head donor molecules between layer pairs. Two beta" polymorphs can be obtained with different degrees of anionic ordering. In one disordered phase, beta"d, with a smaller unit cell, the triiodide anions are disordered over two possible positions in a channel between the donor bilayers, while in the ordered phase, beta"o, the triiodide anions occupy only one of those positions in this channel, leading to the doubling of the unit cell in the layer plane. These results for beta" phases contrast with the kappa polymorph previously reported, for which weaker disorder of the triiodide anions, over two possible orientations with 94 and 6% occupation factors, was observed. While the beta" polymorphs remains metallic down to 1.5 K with a rho300K/rho4K resistivity ratio of 250, the kappa polymorph presents a much smaller resistivity ratio in the range of 4-10 and superconductivity with an onset temperature of 3.5 K. PMID- 27681057 TI - Quantum walks of interacting fermions on a cycle graph. AB - Quantum walks have been employed widely to develop new tools for quantum information processing recently. A natural quantum walk dynamics of interacting particles can be used to implement efficiently the universal quantum computation. In this work quantum walks of electrons on a graph are studied. The graph is composed of semiconductor quantum dots arranged in a circle. Electrons can tunnel between adjacent dots and interact via Coulomb repulsion, which leads to entanglement. Fermionic entanglement dynamics is obtained and evaluated. PMID- 27681058 TI - The enduring legacy of Alfred Gilman senior (1908-1984) to pharmacology and clinical medicine. AB - Alfred Gilman was best known for his co-authorship with Louis Goodman of the seminal textbook on pharmacology The Pharmacological Basis of Therapeutics in 1941. The book made the discipline of pharmacology relevant to clinical medicine by providing a link between the basic medical sciences and the practice of medicine. Gilman was also instrumental in establishing the use of chemotherapy in the treatment of cancer and made important contributions in areas related to renal function, acid-base balance, and diuretics. During the 1960s, he created a first rate department at the newly formed Albert Einstein College of Medicine. A superb lecturer, he commented incisively on issues related to pharmacology, therapeutics, and pathophysiology. Dr Gilman also provided a key link between academia and the pharmaceutical industry by serving as a consultant to several drug firms. The legacy of Alfred Gilman senior was continued by his son, Alfred Goodman Gilman, who became a Nobel Laureate. PMID- 27681059 TI - Dr Jerome Pierce Webster (1888-1974): Surgeon, historian, campaigner, and 'the father of plastic surgery education'. AB - Dr Jerome Pierce Webster is best remembered as the 'founder of plastic surgery education in the United States' on the basis of developing his nation's first plastic surgery residency programme, his role in the founding of the American Board of Plastic Surgery, and, more generally, his influence in professionalising this subspecialty. He also deserves to be remembered for his extensive missionary work in China, his publications as a successful bibliographer, and as an accomplished historian. PMID- 27681060 TI - The music of war: Seven World War 1 composers and their experience of combat. AB - The effect of World War 1 military service on composers has been neglected in comparison with poets and artists. This article describes the wartime service of Arthur Bliss, Ralph Vaughan Williams, Ivor Gurney, EJ Moeran, Gordon Jacob, Patrick Hadley, and Maurice Ravel. The relationship between experiences of combat and the psychological health of these men is examined, with consideration being given to predisposition and possible causative influences of military service on their later careers, examined from individual and societal perspectives. PMID- 27681061 TI - Denis Burkitt: A legacy of global health. AB - When first described in 1958, Burkitt lymphoma was considered by many to be an African curiosity. However, over the next few decades, over 10,000 publications on Burkitt lymphoma would influence many facets of oncology research including immunology, molecular genetics, chemotherapy, and viral oncology. At the time of discovery, its distribution in equatorial Africa was unique; it was where a child was born and lived, and not what race they were, that conveyed the greatest incidence risk. Its association with Epstein-Barr virus brought attention to the possibility that oncogenesis may be influenced by viruses. The influence that Burkitt lymphoma had on furthering oncology is far-reaching, and it is fitting that the physician credited with bringing attention to this disease was himself broad in his influence. Denis Burkitt was a humanitarian surgeon whose work was not limited to Burkitt lymphoma: he instigated a plan to rid an entire Ugandan district of yaws, he designed and created affordable orthopaedic equipment that could be locally produced in Kampala, and he was an early advocate of a high fiber diet. The following article will examine the biography of Denis Burkitt, with a focus on how he was able to further oncology and global health. PMID- 27681062 TI - Treating the fluent aphasias. AB - The origin of the term fluent aphasia is reviewed as well as the characteristics and syndromes of patients presenting with this type of aphasia. Three strategies are presented for describing the impairments and disabilities associated with fluent aphasia: (a) syndrome-based, (b) model-driven, and (c) functionally oriented. Treatment approaches that conform to each of these strategies are discussed. Current methods for assessing the effectiveness of treatment efforts with fluent aphasic patients are described. Some recent findings regarding the causes and characteristics of fluent aphasia are presented with regard to their potential impact on future interventions for these patients. PMID- 27681063 TI - Revealing the competence of aphasic adults through conversation: A challenge to health professionals. AB - The idea that aphasia masks competence normally revealed through conversation forms the basis for a conceptual model thatextends the traditional definition and scope of practice in this field. The model focuses on the long-term, psychosocial consequences of reduced communicative access to social and community life, including reduced access to the service of health professionals. Intervention focuses on training conversation partners (including health professionals) to acqu i re ski I Is that enable the com petence of aphasic adults to be acknowledged and revealed. PMID- 27681064 TI - Augmentative and alternative communication intervention for persons with severe aphasia. AB - Many individuals with severe aphasia are effective in using nonverbal methods of communication to meet their wants and needs. However, their difficulty lies in conveying specific and novel information. Through the use of augmentative and alternative communication (AAC) techniques, severely aphasie individuals can share unique information during interactions. This article focuses on designing AAC intervention programs based on the individual's residual strengths, communication needs, and treatment setting. Individuals who have suffered brainstem strokes or individuals with dysarthria as the primary factor influencing communication are not discussed. Rather, this articlefocuses on individuals with permanent communication disorders due to severe aphasia. PMID- 27681065 TI - Pharmacological approaches to the treatment of aphasia. AB - The catecholaminergic agonists, d-amphetamine and bromocriptine, have shown some promise in the treatment of aphasia. Although studies indicate that patients with aphasia experience language improvement after taking these agents, the experimental controls necessary to prove their efficacy are lacking. Rigorously controlled investigations using a significant number of aphasic patients and a double-blind-placebo controlled design, as well as studies using these drugs as acute care performance enhancers are needed. PMID- 27681066 TI - Drawing and gesture as communication options in a person with severe aphasia. AB - The following case study demonstrates the efficacy of a gestural and graphic treatment approach for an individual with chronic Broca's aphasia. RJ. presented with global aphasia as a result of a stroke in 1985. He had a 2-year history of aphasia therapy without notable results, followed by a 3-year hiatus from any form of therapy. At the request of the patient's daughter, a speech-language pathology (SLP) evaluation was conducted nearly 5 years post onset and over 3 years after any form of communication intervention. Initially R.J. was so severe and perseverative that no formal testing could be administered. A novel, intensive treatment regime commenced, and after 6 weeks of aphasia treatment that focused on gesture and drawing as expressive modalities, R.J. was discharged home a functional communicator. PMID- 27681067 TI - Efficacy of oral reading in the treatment of two patients with chronic Broca's aphasia. AB - Two patients with chronic Broca's aphasia participated in an oral reading treatment program. A multiple baseline design across responses was used. Materials consisted of 90 sentences randomly divided into three groups. Baseline performance was established; then each group of sentences was trained sequentially for 10 sessions. At the end of each session, oral reading performance was probed. For both patients, results indicated increases in accuracy of oral reading of treated materials, with maintenance of performance following termination of treatment. However, generalization to oral reading of untreated material as well as generalization to other oral language tasks were evident only for the aphasic patient with a severe apraxia of speech. PMID- 27681068 TI - Family involvement in the treatment of aphasia. AB - This case study was designed to determine whether a family-based approach to speech language therapy as defined by Andrews and Andrews (1990) provides a cost effective approach to speech language treatment of chronic aphasia. A patient with chronic moderate Broca's aphasia participated in both conventional aphasia treatment and family-based treatment. Resu Its demonstrated that in this patient family-based therapy was at least as effective for communication improvement as traditional aphasia therapy and that it shows promise as a cost-effective adjunct or alternative to traditional treatment in patients with chronic aphasia. PMID- 27681069 TI - Changing models for the health care provider-patient relationship. PMID- 27681070 TI - Testimony presented to the Agency for Health Care Policy and Research. PMID- 27681073 TI - From the Editor. PMID- 27681071 TI - Falls during stroke rehabilitation: A review of the literature. PMID- 27681074 TI - Foreword. PMID- 27681075 TI - Lewis Acid-Catalyzed Denitrogenative Transannulation of Pyridotriazoles with Nitriles: Synthesis of Imidazopyridines. AB - The synthesis of imidazo[1,5-a]pyridines through denitrogenative transannulation of pyridotriazoles with nitriles using BF3.Et2O as catalyst has been described. The combination of solvents (dichlorobenzene-dichloroethane) plays a crucial role in achieving quantitative yields of desired products under metal-free conditions. PMID- 27681076 TI - Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung. AB - BACKGROUND: Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. METHODS: Cap Analysis of Gene Expression (CAGE) is a method used to quantify promoter activities across the whole genome by determining the 5' ends of capped RNA molecules with next-generation sequencing. We performed CAGE on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD), and confirmed the findings by immunohistochemical analysis (IHC) in an independent group (29 SCC and 45 AD). RESULTS: Using the genome-wide promoter activity profiles, we confirmed that the expression of known molecular markers used in IHC for SCC (CK5, CK6, p40 and desmoglein-3) and AD (TTF-1 and napsin A) were different between SCC and AD. We identified two novel marker candidates, SPATS2 for SCC and ST6GALNAC1 for AD, as showing comparable performance and complementary utility to the known markers in discriminating PDSCC and non-lepidic AD. We subsequently confirmed their utility at the protein level by IHC in an independent group. CONCLUSIONS: We identified two genes, SPATS2 and ST6GALNAC1, as novel complemental biomarkers discriminating SCC and AD. These findings will contribute to a more accurate diagnosis of NSCLC, which is crucial for precision medicine for lung cancer. PMID- 27681077 TI - The effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes: a randomised, double-blind, placebo controlled trial. AB - To the best of our knowledge, data on the effects of synbiotic supplementation on markers of insulin metabolism and lipid concentrations in patients with gestational diabetes mellitus (GDM) are scarce. The aim of the current study was to determine the effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in GDM patients. In total, seventy patients with GDM aged 18-40 years were assigned to two groups - the synbiotic group (n 35) and the placebo group (n 35) - in this randomised, double-blind, placebo-controlled trial. Patients in the synbiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2*109 colony-forming units/g each) plus 800 mg inulin for 6 weeks. Fasting blood samples were collected at the beginning and week 6 to quantify related markers. After 6 weeks of intervention, compared with the placebo, synbiotic supplementation led to a significant decrease in serum insulin levels (-1.5 (sd 5.9) v. +4.8 (sd 11.5) uIU/ml, P=0.005), homoeostatic model assessment for insulin resistance (-0.4 (sd 1.3) v. +1.1 (sd 2.7), P=0.003) and homoeostatic model assessment for beta cell function (-5.1 (sd 24.2) v. +18.9 (sd 45.6), P=0.008) and a significant increase in quantitative insulin sensitivity check index (+0.01 (sd 0.01) v. -0.007 (sd 0.02), P=0.02). In addition, synbiotic intake significantly decreased serum TAG (-14.8 (sd 56.5) v. +30.4 (sd 37.8) mg/dl, P<0.001) and VLDL-cholesterol concentrations (-3.0 (sd 11.3) v. +6.1 (sd 7.6) mg/dl, P<0.001) compared with the placebo. Overall, the results of this study demonstrate that taking synbiotic supplements for 6 weeks among patients with GDM had beneficial effects on markers of insulin metabolism, TAG and VLDL-cholesterol concentrations. PMID- 27681079 TI - Acute severe hyponatraemia secondary to polydipsia and associated herbal remedy use. AB - A 47-year-old woman presented with seizures secondary to euvolaemic hyponatraemia. A collateral history revealed recent increased oral fluid intake and increased use of herbal remedies including valerian root over the New Year period. There was no history of psychiatric disease to support psychogenic polydipsia. She responded to careful sodium replacement in the intensive care unit and was discharged with no neurological sequelae. PMID- 27681078 TI - Decreases in Gap Junction Coupling Recovers Ca2+ and Insulin Secretion in Neonatal Diabetes Mellitus, Dependent on Beta Cell Heterogeneity and Noise. AB - Diabetes is caused by dysfunction to beta-cells in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. Gap junction-mediated electrical coupling between beta-cells in the islet plays a major role in coordinating a pulsatile secretory response at elevated glucose and suppressing insulin secretion at basal glucose. Previously, we demonstrated that a critical number of inexcitable cells can rapidly suppress the overall islet response, as a result of gap junction coupling. This was demonstrated in a murine model of Neonatal Diabetes Mellitus (NDM) involving expression of ATP-insensitive KATP channels, and by a multi-cellular computational model of islet electrical activity. Here we examined the mechanisms by which gap junction coupling contributes to islet dysfunction in NDM. We first verified the computational model against [Ca2+] and insulin secretion measurements in islets expressing ATP insensitive KATP channels under different levels of gap junction coupling. We then applied this model to predict how different KATP channel mutations found in NDM suppress [Ca2+], and the role of gap junction coupling in this suppression. We further extended the model to account for stochastic noise and insulin secretion dynamics. We found experimentally and in the islet model that reductions in gap junction coupling allow progressively greater glucose stimulated [Ca2+] and insulin secretion following expression of ATP-insensitive KATP channels. The model demonstrated good correspondence between suppression of [Ca2+] and clinical presentation of different NDM mutations. Significant recoveries in [Ca2+] and insulin secretion were predicted for many mutations upon reductions in gap junction coupling, where stochastic noise played a significant role in the recoveries. These findings provide new understanding how the islet functions as a multicellular system and for the role of gap junction channels in exacerbating the effects of decreased cellular excitability. They further suggest novel therapeutic options for NDM and other monogenic forms of diabetes. PMID- 27681080 TI - Clinical experience with the use of anti-CdtB and anti-vinculin antibodies in patients with diarrhea in Mexico. AB - INTRODUCTION: Circulating anti-CdtB/anti-vinculin antibodies have been validated as biomarkers to distinguish IBS-D from IBD, but there is no experience with them in Latin America. MATERIALS AND METHODS: The analysis was carried out on patients seen at a FGIDs/motility clinic over the last 7 months for diarrhea with abdominal pain and/or bloating who were tested for these antibodies. The patients were diagnosed according to the Rome III criteria or with organic disorders, and those presenting with IBS were further classified as post-infectious (PI) or non PI-IBS. RESULTS: Thirty patients were studied. Positive biomarkers were found in IBS-D and IBS-D Overlap (58.8%) and IBS-M (33.3%), with no differences between PI IBS (71.4%) vs. non-PI-IBS (41.7%) subjects (P=.21). There was no positivity in patients with other FGIDs or organic diarrhea, except for one with small intestinal bacterial overgrowth (SIBO). CONCLUSIONS: Our findings support the use of this test as a first-line diagnostic tool to confirm the presence of IBS-D/IBS M according to the Rome III criteria. PMID- 27681082 TI - Virtual Issue in Memory of Ahmed Zewail. PMID- 27681081 TI - Geographic variations in cervical cancer risk in San Luis Potosi state, Mexico: A spatial statistical approach. AB - BACKGROUND: Worldwide, Cervical Cancer (CC) is the fourth most common type of cancer and cause of death in women. It is a significant public health problem, especially in low and middle-income/Gross Domestic Product (GDP) countries. In the past decade, several studies of CC have been published, that identify the main modifiable and non-modifiable CC risk factors for Mexican women. However, there are no studies that attempt to explain the residual spatial variation in CC incidence In Mexico, i.e. spatial variation that cannot be ascribed to known, spatially varying risk factors. METHODS: This paper uses a spatial statistical methodology that takes into account spatial variation in socio-economic factors and accessibility to health services, whilst allowing for residual, unexplained spatial variation in risk. To describe residual spatial variations in CC risk, we used generalised linear mixed models (GLMM) with both spatially structured and unstructured random effects, using a Bayesian approach to inference. RESULTS: The highest risk is concentrated in the southeast, where the Matlapa and Aquismon municipalities register excessive risk, with posterior probabilities greater than 0.8. The lack of coverage of Cervical Cancer-Screening Programme (CCSP) (RR 1.17, 95 % CI 1.12-1.22), Marginalisation Index (RR 1.05, 95 % CI 1.03-1.08), and lack of accessibility to health services (RR 1.01, 95 % CI 1.00-1.03) were significant covariates. CONCLUSIONS: There are substantial differences between municipalities, with high-risk areas mainly in low-resource areas lacking accessibility to health services for CC. Our results clearly indicate the presence of spatial patterns, and the relevance of the spatial analysis for public health intervention. Ignoring the spatial variability means to continue a public policy that does not tackle deficiencies in its national CCSP and to keep disadvantaging and disempowering Mexican women in regard to their health care. PMID- 27681083 TI - Characterization of Amorphous Oxide Nano-Thick Layers on 316L Stainless Steel by Electron Channeling Contrast Imaging and Electron Backscatter Diffraction. AB - Characterization of the topmost surface of biomaterials is crucial to understanding their properties and interactions with the local environment. In this study, the oxide layer microstructure of plasma-modified 316L stainless steel (SS316L) samples was analyzed by a combination of electron backscatter diffraction and electron channeling contrast imaging using low-energy incident electrons. Both techniques allowed clear identification of a nano-thick amorphous oxide layer, on top of the polycrystalline substrate, for the plasma-modified samples. A methodology was developed using Monte Carlo simulations combined with the experimental results to estimate thickness of the amorphous layer for different surface conditions. X-ray photoelectron spectroscopy depth profiles were used to validate these estimations. PMID- 27681084 TI - Erratum to: Comparative genomics and transcriptomics of Pichia pastoris. PMID- 27681085 TI - Development of Versatile Metal-Organic Framework Functionalized Magnetic Graphene Core-Shell Biocomposite for Highly Specific Recognition of Glycopeptides. AB - Protein N-glycosylation is a ubiquitous and important post-translational modification that has been involved in the development and progression of a series of human-related diseases. Until recently, the highly selective capturing of glycopeptides from complex biosamples was still significant and challenging work due to their changeable structures, ultralow abundance, and strong ion suppressing effect. Here we first report the preparation and characterization of a novel, hydrophilic, porous biocomposite composed of magnetic graphene functionalized with metal-organic frameworks (MOFs) (MG@Zn-MOFs) able to recognize glycopeptides. Thanks to its strong magnetic responsiveness, large specific surface area, excellent biocompatibility, and unique size-exclusion effect, the MG@Zn-MOFs showed outstanding sensitivity and selectivity and good recyclability in glycopeptides analysis. More excitingly, in practical application, 517 N-glycopeptides within 151 unique glycoproteins were clearly identified from human serum (1 MUL) treated with the MG@Zn-MOFs, which is the best result among published reports so far. All the results demonstrate the promising commercialized usage of the biocomposite for the enrichment of glycopeptides in complex samples through a convenient and efficient process. Furthermore, it is anticipated that our strategy may offer promising guidance to develop new biocomposites functionalized with bio-MOFs for glycoproteomic applications. PMID- 27681086 TI - Emergency radiology fellowship training in the USA: a web-based survey of academic programs. AB - Interest in emergency radiology as a distinct subspecialty within radiology continues to rise in the USA and globally. While acute care imaging has been performed since the earliest days of the specialty, fellowship training in emergency radiology is a relatively new phenomenon. The purpose of this study was to examine the current status of emergency radiology training in the USA, using data derived from the official websites of US residency training programs. The most current list of radiology residency programs participating in the 2017 match was obtained from the official Electronic Residency Application Service (ERAS) website. The total number of emergency radiology fellowships was recorded after visiting available websites of each academic radiology program. The total number of subspecialty fellowships offered by each academic radiology program was also recorded. There were 12 confirmed emergency radiology fellowships offered in the USA for a combined total of 22 fellowship positions. Eleven programs were 1 year in duration, with one program offering a one- or two-year option. One hundred eight of the 174 (approximately 62 %) surveyed academic radiology programs offered at least one subspecialty fellowship. Emergency radiology fellowships are on the rise, paralleling the growth of emergency radiology as a distinct subspecialty within radiology. PMID- 27681088 TI - Bandwagons I, too, have known. AB - KEY MESSAGE: Bandwagons come in waves. A plant breeder, just like a surfer, needs to carefully choose which waves to be on. A bandwagon is an idea, activity, or cause that becomes increasingly fashionable as more and more people adopt it. In a 1991 article entitled Bandwagons I Have Known, Professor N. W. Simmonds described several bandwagons that he encountered in his career, beginning with induced polyploidy and mutation breeding and ending with the then-new field of biotechnology. This article reviews and speculates about post-1990 bandwagons in plant improvement, including transgenic cultivars, quantitative trait locus (QTL) mapping, association mapping, genomewide (or genomic) selection, phenomics, envirotyping, and genome editing. The life cycle of a bandwagon includes an excitement phase of hype and funding; a realization phase when the initial hype is either tempered or the initial expectations are found to have been too low; and a reality phase when the useful aspects of a bandwagon become part of mainstream thinking and practice, or when an unsuccessful bandwagon is largely abandoned. During the realization phase, a new bandwagon that draws our attention and gives us renewed optimism typically arises. The most popular bandwagons, such as QTL mapping, are those for which the needed experimental resources are accessible, the required technical knowledge and skills can be easily learned, and the outputs can almost always be reported. The favorite bandwagon of any plant breeder has, in one way or another, resulted from Mendel's seminal discoveries 150 years ago. Our community of plant breeders needs to be continually diligent in welcoming new bandwagons, but also in hopping off from those that do not prove useful. PMID- 27681090 TI - Sensitivity of Folding Molecular Dynamics Simulations to Even Minor Force Field Changes. AB - We examine the sensitivity of folding molecular dynamics simulations on the choice between three variants of the same force field (the AMBER99SB force field and its ILDN, NMR-ILDN, and STAR-ILDN variants). Using two different peptide systems (a marginally stable helical peptide and a beta-hairpin) and a grand total of more than 20 MUs of simulation time we show that even relatively minor force field changes can lead to appreciable differences in the peptide folding behavior. PMID- 27681087 TI - [Alcohol- and substance abuse among mentally ill patients with migration background in Austria]. AB - The refugee movements of the recent years are confronting the health care with new challenges. However, it has turned out that in Austria data on the mental health of migrants are nearly not available. Especially data on the frequency and patterns of comorbid substance abuse of migrants with mental disorders do not exist even from international studies. We analyzed data from 1819 patients (1726 first generation, 93 second generation) treated in the outpatient clinic for transcultural psychiatry and migration related disorders at the Vienna General Hospital: In first-generation migrants the cultural and religious background of the region of origin has the greatest impact on the frequency and the patterns of misused substances. In second-generation migrants the consumer habits approximate to those of the majority of the society. The primary diagnosis plays a minor role. Only patients with personality disorders exhibit higher rates of illicit substance compared with other diagnoses. PMID- 27681089 TI - A novel QTL associated with dwarf bunt resistance in Idaho 444 winter wheat. AB - KEY MESSAGE: A novel QTL, Q.DB.ui-7DS, and the PCR-based markers identified in the current study will accelerate variety development for resistance to dwarf and common bunt of wheat. Dwarf bunt [Tilletia controversa J.G. Kuhn [as 'contraversa'], in Rabenhorst, Hedwigia 13: 188 (1874)] is a destructive disease of wheat (Triticum aestivum L.) that reduces grain yield and quality. A number of distinct genes conferring resistance to dwarf bunt have been used by breeding programs for nearly 100 years. However, few markers were identified that can be used in selection of dwarf bunt resistance. A recombinant inbred line (RIL) population derived from the bunt-resistant germplasm, Idaho 444 (IDO444), and the susceptible cultivar, Rio Blanco, was evaluated for phenotypic reaction to dwarf bunt inoculation in four trials in two locations (USU and USDA) over 3 years. The population was genotyped with the Diversity Arrays Technology (DArT) and the Illumina Infinium 9K iSelect marker platforms. A total of three QTL were detected, and resistant alleles were from IDO444. QTL Q.DB.ui-7DS on 7DS was determined based on the location of a DArT marker wPt-2565 (X116197), which was consistently detected and explained 32 to 56 % of phenotypic variation among the four trials. QTL Q.DB.ui-1A on 1A was detected in three Utah State University (USU) trials and explained 11-15 % of phenotypic variation. QTL Q.DB.ui-2B on 2B was detected in two USU and one United States Department of Agriculture (USDA) trials and explained up to 6 % of phenotypic variation. Two PCR-based markers were developed based on the sequence of wPt-2565 and validated in the RIL population and used in genotyping of dwarf bunt differential lines, known resistance sources, and resistant cultivars. PMID- 27681091 TI - ISVEE 14 Yucatan 2015 14th Symposium of the International Society for Veterinary Epidemiology and Economics. AB - The 14th Symposium of the International Society for Veterinary Epidemiology and Economics (ISVEE 14) was held in Merida, Yucatan, Mexico during 3-7 November. 2015. The purpose of ISVEE 14 Yucatan 2015 was to provide a global forum for graduate students, postdoctoral fellows, junior and senior investigators, as well as health policymakers to exchange information that can advance the fields of veterinary epidemiology and economics, and other disciplines in the health and social sciences. The main theme of ISVEE 14 was Planning Our Future. Human population growth is predicted to increase nearly 50% to 11 billion by 2050, and climate change and changing land use can have an impact on local and global food systems, interactions among humans, wildlife and domestic animals, as well as local, regional, and global public health alerts. How can we help our systems of education, research, and public policy adapt? Are new veterinary graduates and epidemiology practitioners prepared to become active protagonists in the solution of health issues that affect humans and animal populations in a changing environment? What innovative research is needed to understand and enhance the food systems of the future? What are the expected roles or contributions of veterinarians or epidemiology practitioners on future climate change, food systems, and health? Is our profession or discipline leading One Health initiatives? Are there current or new models that make national veterinary services more efficacious and efficient for disease control and eradication? To help us answer these questions, the organizing committee of ISVEE 14 invited five distinguished keynote speakers to share their vision and innovative ideas on education, technological developments, research, and public policy of our future with a concentration in the following five areas: (i) One Health (Jonna Mazet), (ii) climate change (Bernard Bett), (iii) animal health economics (Jonathan Rushton), (iv) national veterinary services (Vitor Goncalves), and (v) animal welfare (Aline Schunemann). This Special Issue includes manuscripts from four of five keynote presentations delivered during ISVEE 14. PMID- 27681094 TI - Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell. AB - Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation. PMID- 27681092 TI - Current ideas on the biology of IGFBP-6: More than an IGF-II inhibitor? AB - IGFBP-6 binds IGF-II with higher affinity than IGF-I and it is a relatively specific inhibitor of IGF-II actions. More recently, IGFBP-6 has also been reported to have IGF-independent effects on cell proliferation, survival, differentiation and migration. IGFBP-6 binds to several ligands in the extracellular space, cytoplasm and nucleus. These interactions, together with activation of distinct intracellular signaling pathways, may contribute to its IGF-independent actions; for example, IGF-independent migration induced by IGFBP 6 involves interaction with prohibitin-2 and activation of MAP kinase pathways. A major challenge for the future is delineating the relative roles of the IGF dependent and -independent actions of IGFBP-6, which may lead to the development of therapeutic approaches for diseases including cancer. PMID- 27681093 TI - Heterozygosity for the rs696217 SNP in the Preproghrelin Gene Predicts Weight Loss After Bariatric Surgery in Severely Obese Individuals. AB - BACKGROUND: Several patients encompass a scarce weight loss after Roux-en-Y gastric bypass (RYGB). As such event is not related to surgical complications, finding markers able to identify "well responders" and to predict weight loss outcome is clinically relevant. Ghrelin regulates appetite and energy balance. Common single nucleotide polymorphisms (SNPs) in its encoding genes have been associated with body weight regulation. Other peptides involved in satiety modulation, like the CD40/CD40L complex, are less explored. METHODS: One hundred, otherwise healthy, obese subjects (aged 45 +/- 11 years, 65 females, BMI 48.0 +/- 0.7 kg/m2) were sequentially enrolled in years 2014-2015. SNPs rs2241766 for adiponectin gene, rs490683 for ghrelin receptor, rs696217 and rs27647 for the preproghrelin/ghrelin gene, and rs1126535 for the CD40L gene were determined on DNA extracted from circulating lymphomonocytes. Patients were reevaluated at 6 (n = 100), 26 (n = 91), and 52 weeks (n = 79) after RYGB. RESULTS: Subjects carrying the rs696217 T allele encompassed a significantly greater reduction in BMI 52 weeks after surgery (GG vs GT 30.5 +/- 1.1 vs 38.1 +/- 2.1 %; p < 0.001). Carrying the rs1126535 C allele in the CD40L gene was associated with a significantly lower BMI reduction at week 52 (TT vs CT 33.2 +/- 1.1 vs 28.1 +/- 2.3 %, p = 0.049). rs490683 and rs27647 SNPs of ghrelin and rs2241766 for adiponectin gene did not show any difference between carriers and non-carriers of the mutant allele. CONCLUSION: Carrying a G to T substitution in rs696217 (preproghrelin gene) seems to mark a successful weight loss outcome; we also report for the first time that the rs1126535 C allele (CD40L gene) may predict a worse response to bariatric surgery. PMID- 27681096 TI - Erratum to "The course and distribution of the infra patellar nerve in relation to ACL reconstruction" [Knee 22 (2015) 384-388]. PMID- 27681095 TI - Evaluation of the anti-diarrheal activity of the leaf extract of Croton macrostachyus Hocsht. ex Del. (Euphorbiaceae) in mice model. AB - BACKGROUND: Traditional healers in Ethiopia use a wide range of medicinal plants with antidiarrheal properties. Among these, Croton macrostachyus is one such plant claimed to have an antidiarrheal activity in Ethiopian folklore medicine. Previous studies showed that the crude extract is endowed with the claimed property. The present study was undertaken to further the claim by screening different fractions for the said activity so that it could serve as a basis for subsequent studies. METHODS: The fractions were obtained by successive extraction in soxhlet apparatus with solvents of different polarity (chloroform & methanol) followed by cold maceration of the deposit of the methanol fraction with distilled water. The antidiarrheal activity was evaluated using castor oil induced diarrheal model, charcoal meal test and anti-enteropooling test in mice. The test groups received various doses (300, 400, 500 mg/kg and an additional dose of 1000 mg/kg for the aqueous fraction) of the fractions, whereas positive controls received either Loperamide (3 mg/kg) or Atropine (5 mg/kg) and negative controls received vehicle (10 ml/kg). RESULTS: In the castor oil induced model, the chloroform (at all test doses) and methanol (at 400 & 500 mg/kg) fractions significantly delayed diarrheal onset, decreased stool frequency and weight of feces. The aqueous fraction was however devoid of significant effect at all the tested doses. Chloroform and methanol fractions produced a significant dose dependent decline in the weight and volume of intestinal contents while the aqueous fraction did not have a significant effect. All the fractions produced a significant anti-motility effect either at all doses (chloroform fraction) or at middle and higher doses (methanol and aqueous fractions). CONCLUSION: The present study demonstrated that the chloroform and methanol fractions possessed significant anti-diarrheal activity. Nevertheless, the aqueous fraction showed only significant anti-motility effect at the higher dose (1000 mg/kg) employed in the study. PMID- 27681098 TI - Sleep Disturbances Induced by Stimulants in Children with Attention-Deficit Hyperactivity Disorder. PMID- 27681099 TI - Thoughts on relief for atomic bomb survivors since Obama's visit to Hiroshima. PMID- 27681097 TI - Relationship between mediation analysis and the structured life course approach. AB - Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). PMID- 27681100 TI - Post-cardiac arrest mortality is declining in the UK. PMID- 27681101 TI - The Impact of the Security Competency on "Self-Efficacy in Information Security" for Effective Health Information Security in Iran. AB - The security effectiveness based on users' behaviors is becoming a top priority of Health Information System (HIS). In the first step of this study, through the review of previous studies 'Self-efficacy in Information Security' (SEIS) and 'Security Competency' (SCMP) were identified as the important factors to transforming HIS users to the first line of defense in the security. Subsequently, a conceptual model was proposed taking into mentioned factors for HIS security effectiveness. Then, this quantitative study used the structural equation modeling to examine the proposed model based on survey data collected from a sample of 263 HIS users from eight hospitals in Iran. The result shows that SEIS is one of the important factors to cultivate of good end users' behaviors toward HIS security effectiveness. However SCMP appears a feasible alternative to providing SEIS. This study also confirms the mediation effects of SEIS on the relationship between SCMP and HIS security effectiveness. The results of this research paper can be used by HIS and IT managers to implement their information security process more effectively. PMID- 27681104 TI - Erratum to: Botulinum Toxin Injection for Treatment of Chronic Anal Fissure: Is There Any Dose-Dependent Efficiency? A Meta-Analysis. PMID- 27681102 TI - Tumor Static Concentration Curves in Combination Therapy. AB - Combination therapies are widely accepted as a cornerstone for treatment of different cancer types. A tumor growth inhibition (TGI) model is developed for combinations of cetuximab and cisplatin obtained from xenograft mice. Unlike traditional TGI models, both natural cell growth and cell death are considered explicitly. The growth rate was estimated to 0.006 h-1 and the natural cell death to 0.0039 h-1 resulting in a tumor doubling time of 14 days. The tumor static concentrations (TSC) are predicted for each individual compound. When the compounds are given as single-agents, the required concentrations were computed to be 506 MUg . mL-1 and 56 ng . mL-1 for cetuximab and cisplatin, respectively. A TSC curve is constructed for different combinations of the two drugs, which separates concentration combinations into regions of tumor shrinkage and tumor growth. The more concave the TSC curve is, the lower is the total exposure to test compounds necessary to achieve tumor regression. The TSC curve for cetuximab and cisplatin showed weak concavity. TSC values and TSC curves were estimated that predict tumor regression for 95% of the population by taking between-subject variability into account. The TSC concept is further discussed for different concentration-effect relationships and for combinations of three or more compounds. PMID- 27681105 TI - Influence of volumetric reduction factor during ozonation of nanofiltration concentrates for wastewater reuse. AB - Global population growth induces increased threat on drinking water resources. One way to address this environmental issue is to reuse water from wastewater treatment plant. The presence of pathogenic microorganisms and potentially toxic organic micropollutants does not allow a direct reuse of urban effluents. Membrane processes such reverse osmosis (RO) or nanofiltration (NF) can be considered to effectively eliminate these pollutants. The integration of membrane processes involves the production of concentrated retentates which require being disposed. To date, no treatment is set up to manage safely this pollution. This work focuses on the application of ozonation for the treatment of NF retentates in the framework of the wastewater reuse. Ozonation is a powerful oxidation process able to react and degrade a wide range of organic pollutants. Four pharmaceutical micropollutants were selected as target molecules: acetaminophen, carbamazepine, atenolol and diatrozic acid. This study highlighted that NF represents a viable alternative to the commonly used RO process ensuring high retention at much lower operating costs. Ozonation appears to be effective to degrade the most reactive pollutants toward molecular ozone but is limited for the reduction of refractory ozone pollutants due to the inhibition of the radical chain by the high content of organic matter in the retentates. The ozonation process appears to be a promising NF retentate treatment, but additional treatments after ozonation are required to lead to a zero liquid discharge treatment scheme. PMID- 27681103 TI - Relation of Transcriptional Factors to the Expression and Activity of Cytochrome P450 and UDP-Glucuronosyltransferases 1A in Human Liver: Co-Expression Network Analysis. AB - Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles (n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs. The relationship among 17 defined TFs, CYPs/UGTs expression, and activity were evaluated in 30 liver samples from Chinese patients. The positive controls (e.g., PPARA, NR1I2, NR1I3) and hub TFs (NFIA, NR3C2, and AR) in the GreysWGCNA Module were significantly and positively associated with CYPs/UGTs expression. And the cancer- or inflammation-related TFs (TEAD4, NFKB2, and NFKB1) were negatively associated with mRNA expression of CYP2C9/CYP2E1/UGT1A9. Furthermore, the effect of NR1I2, NR1I3, AR, TEAD4, and NFKB2 on CYP450/UGT1A gene transcription translated into moderate influences on enzyme activities. To our knowledge, this is the first study to integrate Gene Expression Omnibus (GEO) datasets and supervised weighted correlation network analysis (sWGCNA) for defining TFs potentially related to CYPs/UGTs. We detected several novel TFs involved in the regulatory network of hepatic CYPs and UGTs in humans. Further validation and investigation may reveal their exact mechanism of CYPs/UGTs regulation. PMID- 27681106 TI - New evidence on the formation of oxidizing species in corona discharge in contact with liquid and their reactions with organic compounds. AB - The objective of these investigations is to understand in more detail how organic compounds in water are degraded during plasma treatment. The formation of oxidizing species (ozone (O3), hydrogen peroxide (H2O2) and hydroxyl radicals (OH)) in a pulsed corona discharge in contact with liquid is investigated. The degradation of a target organic compound (methylparaben) in aqueous solution was increased when combining plasma treatment with ozonation, using the O3 generated in the discharge. Enhanced mass transfer of O3 obtained in this plasma+O3 configuration leads to a six fold increase of MeP oxidation rate. The evolution of oxidants concentration during treatment of MeP solutions provides information on their consumption in reactions with MeP and its oxidation products. The correlation of MeP degradation results (MeP removal and mineralization) with O3 consumption and the identified reaction products confirms that although O3 plays an important role in the degradation, for the mineralization OH radicals have an essential contribution. The concentration of OH radicals is diminished in the solutions containing MeP as compared to plasma-treated water, indicating OH consumption in reactions with the target compound and its degradation products. The concentration of H2O2 in the liquid can be either increased or reduced in the presence of MeP, depending on its initial concentration. On the one hand, decomposition of H2O2 by OH or O3 is suppressed in the presence of MeP, but on the other hand less OH radicals are available for its formation. PMID- 27681107 TI - Pay attention to non-wastewater emission pathways of pharmaceuticals into environments. AB - Pharmaceuticals have been widely detected in the aquatic environment and demonstrated to be potential risks to humans and the environment. Understanding emission pathways of pharmaceuticals is essential to the control of pharmaceutical contamination for environmental management. The present study is aimed at testing the hypothesis that non-wastewater pathway is also significant to the emission of pharmaceuticals into the environment. To this end, we compared the actual production with the amount of 12 antibiotics obtained by back calculation from sewage concentrations in Beijing, Guangzhou and Chongqing. The results showed that for over a half of investigated antibiotics, the emission through non-wastewater pathways accounted for approximately 30-80% of the total emission, varying with individual antibiotics. It was revealed that non wastewater emission pathways could be of significance for pharmaceuticals emitted into the environment, of which disposed by household waste could be among the most important non-wastewater pathways. PMID- 27681108 TI - The effect of the number of alkyl substituents on imidazolium ionic liquids phytotoxicity and oxidative stress in spring barley and common radish seedlings. AB - Increasing amounts of two ILs: 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6] and 1-butyl-2,3-dimethylimidazolium hexafluorophosphate [BMMIM][PF6], were introduced to soil in which spring barley (Hordeum vulgare) and common radish (Raphanus sativus L. subvar. radicula Pers.) seedlings were cultivated, in order to evaluate the phytotoxicity of ionic liquids with imidazolium cation with two or three alkyl substituents attached. The results of the study i.e. the inhibition of the length of plants and their roots, as well as the yield of fresh weight of plants, clearly showed that differences in the number of substituents did not affect the toxicity of these ILs. Although, radish was more resistant to the applied ionic liquids than barley. Ionic liquids led to a decrease in the content of all assimilation pigments and induced oxidative stress in the plants, as showed by an increase in malondialdehyde (MDA) content, and changes in the level of H2O2 and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). The best biomarkers of oxidative stress in both plants were the changes in chlorophyll content and the increase in POD activity. Both spring barley and radish exposed to [BMIM][PF6] and [BMMIM][PF6] accumulated a large amount of fluoride ions, which further increased the toxicity of these compounds for both plants. PMID- 27681109 TI - Combined cyto/genotoxic activity of a selected antineoplastic drug mixture in human circulating blood cells. AB - Antineoplastic drugs are highly cytotoxic chemotherapeutic agents that can often interfere directly or indirectly with the cell's genome. In an environmental or medical setting simultaneous exposure may occur. Such multiple exposures may pose a higher risk than it could be assumed from the studies evaluating the effect of a single substance. Therefore, in the present study we tested the combined cyto/genotoxicity of a mixture of selected antineoplastic drugs with different mechanisms of action (5-fluorouracil, etoposide, and imatinib mesylate) towards human lymphocytes in vitro. The results suggest that the selected antineoplastic drug mixture is potentially cyto/genotoxic and that it can induce cell and genome damage even at low concentrations. Moreover, the changes in the measured oxidative stress parameters suggest the participation of reactive oxygen species in the cyto/genotoxicity of the selected mixture. The obtained results indicate not only that such mixtures may pose a risk to cell and genome integrity, but also that single compound toxicity data are not sufficient for the predicting toxicity in a complex environment. Altogether, the results emphasise the need for further toxicological screening of antineoplastic drug mixtures, especially at low environmentally relevant concentrations, as to avoid any possible adverse effects on the environment and human health. PMID- 27681110 TI - Assessing the combination of iron sulfate and organic materials as amendment for an arsenic and copper contaminated soil. A chemical and ecotoxicological approach. AB - The efficiency of combining iron sulfate and organic amendments (paper mill sludge, olive mill waste compost and olive tree pruning biochar) for the remediation of an As- and Cu-contaminated soil was evaluated. Changes in As and Cu fractionation and solubility due to the application of the amendments was explored by leachate analysis, single and sequential extractions. Also, the effects on Arrhenatherum elatius growth, germination of Lactuca sativa and toxicity to the bacteria Vibrio fischeri were assessed. The combination of iron sulfate and the organic amendments efficiently reduced As solubility and availability through the formation of amorphous iron oxides, while organic matter did not seem to mobilize As. At the same time, copper fractionation was strongly affected by soil pH and organic matter addition. The soil pH significantly influenced both As and Cu mobility. Within all the amendments tested, FeSO4 in combination with compost showed to be the most suitable treatment for the overall remediation process, as it reduced As and Cu availability andenhanced soil nutrient concentrations and plant growth. In sipte of contradictory trends between chemical analyses and ecotoxicity tests, we can still conclude that the application of organic amendments in combination with reactive iron salts is a suitable approach for the remediation of soils contaminated by Cu and As. PMID- 27681111 TI - Evaluation of the extraction efficiency for the Hypoaspis aculeifer reproduction test in the context of soil quality assessment. AB - The standardized bioassay using the predatory mite Hypoaspis aculeifer (TG 226; as reported by OECD 2008) has already proven its usefulness for the assessment of chemicals. While included in the regulatory assessment scheme of pesticides as a non-target arthropod, it has still been rarely used for the assessment of soils or complex matrices of unknown quality. For such an objective, the extraction of both adults and juveniles from soil is a necessary and crucial step to get reliable data, but may be influenced by the characteristics of the tested soils or matrices. This technical note focuses on this specific protocol point. Extraction ratios of adults and of different reproductive outputs were evaluated in soils of different textures. Recommendations on the extraction of H. aculeifer in the standardization process within ISO/TC 190 are here provided. PMID- 27681112 TI - Effects of thalamic hemorrhagic lesions on explicit and implicit learning during the acquisition and retrieval phases in an animal model of central post-stroke pain. AB - Hemorrhagic stroke has many symptoms, including central pain, learning and memory impairments, motor deficits, language problems, emotional disturbances, and social maladjustment. Lesions of the ventral basal complex (VBC) of the thalamus elicit thermal and mechanical hyperalgesia, forming an animal model of central post-stroke pain (CPSP). However, no research has yet examined the involvement of learning and memory in CPSP using an animal model. The present study examined whether VBC lesions affect motor function, conditioned place preference (CPP; implicit memory), and spatial learning (explicit memory) in the acquisition and retrieval phases. The results showed that rats with VBC lesions exhibited thermal hyperalgesia in the acquisition and retrieval phases, indicating that these lesions can induce CPSP. During these phases, the rats with VBC lesions exhibited enhanced (morphine-induced) CPP learning. These lesions did not affect the rats' total distance travelled, time spent, or velocity in the spatial learning tasks. The lesions also did not affect motor function in the rotarod task. Altogether, VBC lesions resulted in CPSP and facilitated CPP (implicit memory). However, the lesions did not affect spatial learning (explicit memory) or motor function. The relationship between CPSP and learning and memory is important for patients who suffer from such central pain. The implications of the present study may provide insights into helping reduce CPSP and its associated symptoms. PMID- 27681113 TI - Resting Heart Rate and Long-term Outcomes Among the African American Population: Insights From the Jackson Heart Study. AB - Importance: Increased resting heart rate is associated with worse outcomes in studies of mostly white populations, but its significance is not well established in African Americans persons whose cardiac comorbidities and structural abnormalities differ. Objective: To study the prognostic utility of heart rate in a community-based African American cohort in the Jackson Heart Study. Design, Setting, and Participants: A total of 5261 participants in the Jackson Heart Study, a prospective, community-based study in Jackson, Mississippi, were evaluated. Baseline heart rate was assessed by quintiles and as a continuous variable. All participants with baseline heart rate documented by a 12-lead electrocardiogram without pacing or atrial fibrillation noted on their baseline Jackson Heart Study examination were included in the study. Follow-up began September 26, 2000, and was completed December 31, 2011. Data analysis was performed from July to October 2015. Main Outcomes and Measures: Unadjusted and adjusted associations between heart rate and all-cause mortality and heart failure hospitalization using Cox proportional hazards regression models. Results: Of the 5261 individuals included in the analysis, 1921 (36.5%) were men; median (25th-75th percentile) age was 55.7 (45.4-64.8) years. Median (25th-75th percentile) baseline heart rate was 63 beats per minute (bpm) (57-71 bpm). The highest heart rate quintile (73-118 bpm) had higher rates of diabetes (398 [37.4%]; P < .001) and hypertension (735 [69.1%]; P < .001), higher body mass index (median [IQR], 32.4 [28.1-38.3]; P < .001), less physical activity (0 hours per week, 561 [52.8%]; P < .001), and lower beta-blocker use (73 [6.9%]; P < .001) compared with lower quintiles. Caffeine intake (from 80.7 to 85.5 mg/d; P = .57) and left ventricular ejection fraction (from 62% to 62.3%; P = .01) were similar between groups. As a continuous variable, elevated heart rate was associated with increased mortality and heart failure hospitalizations, with adjusted hazard ratios for every 5-bpm increase of 1.14 (95% CI, 1.10-1.19) and 1.10 (95% CI, 1.05-1.16), respectively. Similar patterns were observed in comparisons between the highest and lowest quintiles. Conclusions and Relevance: Higher baseline heart rate was associated with increased mortality and heart failure hospitalizations among African American participants in the Jackson Heart Study. These findings are similar to those seen in white populations, but further study is needed to understand whether African American individuals benefit from interventions targeting heart rate reduction. PMID- 27681114 TI - Augmented Renal Clearance in Patients With Febrile Neutropenia is Associated With Increased Risk for Subtherapeutic Concentrations of Vancomycin. AB - BACKGROUND: Augmented renal clearance (ARC) has frequently been observed in critically ill patients. The risk factors for ARC in patients, including those in the general ward, and their influences on vancomycin (VCM) treatment remain unclear. The aims of this study were to investigate the risk factors for ARC and to evaluate the influence of ARC on the pharmacokinetic parameters of VCM. METHODS: This study included a total of 292 patients with VCM treatment who had normal serum creatinine concentrations. ARC was defined by an estimated creatinine clearance >=130 mL.min.1.73 m. The risk factors for ARC were determined with stepwise logistic regression analysis. The pharmacokinetic parameters of VCM were estimated through the Bayesian method using a 2 compartment model. RESULTS: ARC was observed in 48 patients (16.4%). Age <=65 years [odds ratio (OR): 5.77; 95% CI: 2.89-11.97; P < 0.0001], brain injury (OR: 5.11; 95% CI: 1.49-17.57; P = 0.0086), febrile neutropenia (OR: 2.76; 95% CI: 1.11-6.67; P = 0.0254), and a mean volume of infusion fluid >=1500 mL/d (OR: 2.53; 95% CI: 1.27-5.16; P = 0.0091) were independent risk factors for the occurrence of ARC. The patients with ARC exhibited higher VCM clearance values than the non-ARC patients. The median trough serum concentrations of VCM were 7.4 (interquartile range: 5.2-11.6) mcg/mL in the ARC patients and 12.2 (8.9-16.3) mcg/mL in the non-ARC patients (P < 0.0001). Subtherapeutic trough concentrations of VCM (<10.0 mcg/mL) were found in 68.8% of the ARC patients and in 32.8% of the non-ARC patients (P < 0.0001). CONCLUSIONS: This observational study investigated the influence of febrile neutropenia on the emergency of ARC for the first time. ARC was strongly associated with VCM pharmacokinetics, and two-thirds of the ARC patients had subtherapeutic VCM concentrations. In patients with ARC, individualized dosing regimens are required to achieve the target trough concentration. PMID- 27681115 TI - Treating Infectious Keratitis. PMID- 27681116 TI - Oxytocin, cortisol and 3,4-methylenedioxymethamphetamine: neurohormonal aspects of recreational 'ecstasy'. AB - Most research into 3,4-methylenedioxymethamphetamine (MDMA) has debated its psychobiological effects in relation to neurotransmission. This article debates the contributory roles of the neurohormones oxytocin and cortisol for their psychobiological effects in humans. The empirical literature on these neurohormones is reviewed and suggestions for future research outlined. Acute MDMA or 'ecstasy' can generate increased levels of oxytocin and cortisol, and these neurohormonal changes may be important for its mood-enhancing and energy activation effects in humans. However, an initial finding of enhanced sociability correlating with oxytocin levels has not been replicated. Potential reasons are debated. There may be dynamic interactions between the two neurohormones, with greater activation under cortisol, facilitating stronger positive feelings under oxytocin. Chronic regular use of MDMA can adversely affect cortisol in several ways. Regular users show increased cortisol in 3-month hair samples, changes to the cortisol awakening response, and indications of greater daily stress. Furthermore, these cortisol findings suggest changes to the hypothalamic pituitary-adrenal axis. The effects of chronic MDMA usage on oxytocin still need to be investigated. It is concluded that the neurohormones oxytocin and cortisol contribute in various ways to the psychobiological effects of recreational ecstasy/MDMA. PMID- 27681117 TI - Novel Chromosome 5 Inversion Associated With PDGFRB Rearrangement in Hypereosinophilic Syndrome. PMID- 27681119 TI - Manufacturer failed to disclose faulty device in rivaroxaban trial. PMID- 27681118 TI - Role of the haemodynamic mapping in varicose vein surgery of lower limbs. AB - AIM: To demonstrate the importance of preoperative ultrasound haemodynamic mapping of venous system in surgery of varicose veins. MATERIALS AND METHODS: Doppler ultrasound evaluation of haemodynamic features of lower limb venous system according to Franceschi's subdivision. DISCUSSION: The importance of Doppler mapping in varicose veins surgery shows a similarity with the Plebographic classification of venous system developed by W. Hach. The study also reassesses the role of varicectomy in the surgery of varicose veins. CONCLUSIONS: Preoperative Doppler ultrasound mapping is essential to avoid accident and prevent recurrence of varicose veins. KEY WORDS: Doppler US, Surgery, Great Saphenous Vein, Varicose Veins, Stripping. PMID- 27681120 TI - Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis. AB - : Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. This study documents how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using in vitro KS and PEL cells as models. The presence of the lipoxin A4 receptor/formyl peptidyl receptor (ALX/FPR) in KS patient tissue sections and in vitro KS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treating de novo KSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing the levels of NF-kappaB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene deletion revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral microRNA (miRNA) cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. This study provides a new insight into the potential treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin. IMPORTANCE: KSHV infection has been shown to upregulate several host proinflammatory factors, which aid in its survival and pathogenesis. The influence of KSHV infection on anti-inflammatory molecules is not well studied. Since current treatment methods for KS and PEL are fraught with unwanted side effects and low efficiency, the search for new therapeutics is therefore imperative. The use of nature's own molecule lipoxin as a drug is promising. This study opens up new domains in KSHV research focusing on how the virus modulates lipoxin secretion and warrants further investigation of the therapeutic potential of lipoxin using in vitro cell models for KS and PEL. PMID- 27681121 TI - Immune- and Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants of Herpes Simplex Virus-Induced Generalized Infections and Acute Liver Failure. AB - : The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV 1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-alphabetagammaR-/- mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-alphabetagammaR-/- (AG129) and wild-type (WT; 129SvEv) mice to probe the underlying IFN-dependent mechanisms that control HSV-1 pathogenesis. After infection, WT mice with either IFN-alphabetagammaR-/- or WT marrow exhibited comparable survival, while IFN-alphabetagammaR-/- mice with WT marrow had a significant survival advantage over their counterparts with IFN alphabetagammaR-/- marrow. Furthermore, using bioluminescent imaging to maximize data acquisition, we showed that the transfer of IFN-competent hematopoietic cells controlled HSV-1 replication and damage in the livers of IFN alphabetagammaR-/- mice. Consistent with this, the inability of IFN alphabetagammaR-/- immune cells to control liver infection in IFN-alphabetagammaR /- mice manifested as profoundly elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels, indicative of severe liver damage. In contrast, IFN-alphabetagammaR-/- mice receiving WT marrow exhibited only modest elevations of AST and ALT levels. These studies indicate that IFN responsiveness of the immune system is a major determinant of viral tropism and damage during visceral HSV infections. IMPORTANCE: Herpes simplex virus 1 (HSV-1) infection is an incurable viral infection with the most significant morbidity and mortality occurring in neonates and patients with compromised immune systems. Severe pathologies from HSV include the blindness-inducing herpetic stromal keratitis, highly debilitating and lethal herpes simplex encephalitis, and generalized infections that can lead to herpes simplex virus-induced acute liver failure. While immune compromise is a known factor, the precise mechanisms that lead to generalized HSV infections are unknown. In this study, we used and developed a mouse model system in combination with real-time bioluminescence imaging to demonstrate the relative importance of the immune and nonimmune compartments for containing viral spread and promoting host survival after corneal infection. Our results shed light on the pathogenesis of HSV infections that lead to generalized infection and acute liver failure. PMID- 27681122 TI - Structure of Aichi virus 1 and its empty particle: clues towards kobuvirus genome release mechanism. AB - : Aichi virus 1 (AiV-1) is a human pathogen from the Kobuvirus genus of the Picornaviridae family. Worldwide, 80-95% of adults have antibodies against the virus. AiV-1 infections are associated with nausea, gastroenteritis, and fever. Unlike most picornaviruses, kobuvirus capsids are composed of only three types of subunits: VP0, VP1, and VP3. Here we present the structure of the AiV-1 virion determined to a resolution of 2.1 A using X-ray crystallography. The surface loops puff of VP0 and knob of VP3 in AiV-1 are shorter than those in other picornaviruses. Instead, the 42-residue-long BC-loop of VP0 forms the most prominent surface feature of the AiV-1 virion. We determined the structure of AiV 1 empty particle to a resolution of 4.2 A using cryo-electron microscopy. The empty capsids are expanded relative to the native virus. The N-terminal arms of capsid proteins VP0, which mediate contacts between the pentamers of capsid protein protomers in the native AiV-1 virion, are disordered in the empty capsid. Nevertheless, the empty particles are stable, at least in vitro, and do not contain pores that might serve as channels for genome release. Therefore, extensive and probably reversible local reorganization of AiV-1 capsid is required for its genome release. IMPORTANCE: Aichi virus 1 (AiV-1) is a human pathogen that can cause diarrhea, abdominal pain, nausea, vomiting, and fever. AiV-1 is identified in environmental screening studies with higher frequency and greater abundance than other human enteric viruses. Accordingly, 80-95% of adults worldwide have suffered from AiV-1 infections. We determined the structure of the AiV-1 virion. Based on the structure, we show that antiviral compounds that were developed against related enteroviruses are unlikely to be effective against AiV 1. The surface of the AiV-1 virion has a unique topology distinct from other related viruses from the Picornaviridae family. We also determined that AiV-1 capsids form compact shells even after genome release. Therefore, AiV-1 genome release requires large localized and probably reversible reorganization of the capsid. PMID- 27681123 TI - Single-Nucleotide Resolution Mapping of Hepatitis B Virus Promoters in Infected Human Livers and Hepatocellular Carcinoma. AB - : Hepatitis B virus (HBV) is a major cause of liver diseases, including hepatocellular carcinoma (HCC), and more than 650,000 people die annually due to HBV-associated liver failure. Extensive studies of individual promoters have revealed that heterogeneous RNA 5' ends contribute to the complexity of HBV transcriptome and proteome. Here, we provide a comprehensive map of HBV transcription start sites (TSSs) in human liver, HCC, and blood, as well as several experimental replication systems, at a single-nucleotide resolution. Using CAGE (cap analysis of gene expression) analysis of 16 HCC/nontumor liver pairs, we identify 17 robust TSSs, including a novel promoter for the X gene located in the middle of the gene body, which potentially produces a shorter X protein translated from the conserved second start codon, and two minor antisense transcripts that might represent viral noncoding RNAs. Interestingly, transcription profiles were similar in HCC and nontumor livers, although quantitative analysis revealed highly variable patterns of TSS usage among clinical samples, reflecting precise regulation of HBV transcription initiation at each promoter. Unlike the variety of TSSs found in liver and HCC, the vast majority of transcripts detected in HBV-positive blood samples are pregenomic RNA, most likely generated and released from liver. Our quantitative TSS mapping using the CAGE technology will allow better understanding of HBV transcriptional responses in further studies aimed at eradicating HBV in chronic carriers. IMPORTANCE: Despite the availability of a safe and effective vaccine, HBV infection remains a global health problem, and current antiviral protocols are not able to eliminate the virus in chronic carriers. Previous studies of the regulation of HBV transcription have described four major promoters and two enhancers, but little is known about their activity in human livers and HCC. We deeply sequenced the HBV RNA 5' ends in clinical human samples and experimental models by using a new, sensitive and quantitative method termed cap analysis of gene expression (CAGE). Our data provide the first comprehensive map of global TSS distribution over the entire HBV genome in the human liver, validating already known promoters and identifying novel locations. Better knowledge of HBV transcriptional activity in the clinical setting has critical implications in the evaluation of therapeutic approaches that target HBV replication. PMID- 27681127 TI - Ubiquitination up-regulates influenza virus polymerase function. AB - : The influenza A virus polymerase plays an essential role in the virus lifecycle, directing synthesis of viral mRNAs and genomes. It is a trimeric complex composed of subunits PA, PB1, and PB2 and associates with viral RNAs and nucleoprotein (NP) to form higher order ribonucleoprotein (RNP) complexes. The polymerase is regulated temporally over the course of infection to ensure coordinated expression of viral genes as well as replication of the viral genome. Various host factors and processes have been implicated in regulation of the IAV polymerase function, including post-translational modifications, however the mechanisms are not fully understood. Here we demonstrate that ubiquitination plays an important role in stimulating polymerase activity. We show that all protein subunits in the RNP are ubiquitinated, but ubiquitination does not significantly alter protein levels. Instead, ubiquitination and an active proteasome enhance polymerase activity. Expressing ubiquitin up-regulates polymerase function in a dose-dependent fashion causing increased accumulation of vRNA, cRNA and mRNA and enhanced viral gene expression during infection. Ubiquitin expression directly affects polymerase activity independent of NP or RNP assembly. Ubiquitination and the ubiquitin-proteasome pathway play key roles during multiple stages of influenza virus infection, and data presented here now demonstrate that these processes modulate viral polymerase activity independent of protein degradation. IMPORTANCE: The cellular ubiquitin-proteasome pathway impacts steps during the entire influenza virus life cycle. Ubiquitination suppresses replication by targeting viral proteins for degradation and stimulating innate antiviral signaling pathways. Ubiquitination also enhances replication by facilitating viral entry and virion disassembly. We identify here an addition pro-viral role of the ubiquitin-proteasome system, showing that all of the proteins in the viral replication machinery are subject to ubiquitination and this is crucial for optimal viral polymerase activity. Manipulating the ubiquitin machinery for therapeutic benefit is therefore likely to disrupt the function of multiple viral proteins at stages throughout the course of infection. PMID- 27681126 TI - Suppression of Host Innate Immune Response by Hepatitis C Virus via Induction of Autophagic Degradation of TRAF6. AB - : Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an important adaptor molecule that mediates the TNFR family and interleukin-1 (IL 1)/Toll-like receptor (TLR) signaling cascades. These pathways are important for the host to control viral infections. In this report, we demonstrated that hepatitis C virus (HCV) depleted TRAF6 from its host cells through a posttranslational mechanism. This depletion was independent of proteasomes, as it was not affected by the proteasome inhibitor MG132, but it was suppressed by bafilomycin A1, which led to the association of TRAF6 with autophagosomes. As bafilomycin A1 is a vacuolar ATPase inhibitor that inhibits autophagic protein degradation, these results suggested that HCV depleted TRAF6 via autophagy. The degradation of TRAF6 was apparently mediated by the p62 sequestosome protein, which is a factor important for selective autophagy, as it could bind to TRAF6 and its silencing stabilized TRAF6. The depletion of TRAF6 suppressed activation of NF-kappaB and induction of proinflammatory cytokines and enhanced HCV replication. In contrast, the overexpression of TRAF6 suppressed HCV replication. These results revealed a novel mechanism that was used by HCV to disrupt the host innate immune responses for viral replication and persistence. IMPORTANCE: HCV can cause severe liver diseases and is one of the most important human pathogens. It establishes chronic infections in the great majority of patients that it infects, indicating that it has evolved sophisticated mechanisms to evade host immunity. TRAF6 is an important signaling molecule that mediates activation of NF kappaB and expression of proinflammatory cytokines and interferons. In this study, we found that HCV infection suppressed the host innate immune response through the induction of autophagic degradation of TRAF6. This finding provided important information for further understanding how HCV evades host immunity to establish persistence. PMID- 27681124 TI - Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia. AB - : Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression. IMPORTANCE: Many aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection. PMID- 27681125 TI - The Splicing History of an mRNA Affects Its Level of Translation and Sensitivity to Cleavage by the Virion Host Shutoff Endonuclease during Herpes Simplex Virus Infections. AB - : During lytic herpes simplex virus (HSV) infections, the virion host shutoff (Vhs) (UL41) endoribonuclease degrades many cellular and viral mRNAs. In uninfected cells, spliced mRNAs emerge into the cytoplasm bound by exon junction complexes (EJCs) and are translated several times more efficiently than unspliced mRNAs that have the same sequence but lack EJCs. Notably, most cellular mRNAs are spliced, whereas most HSV mRNAs are not. To examine the effect of splicing on gene expression during HSV infection, cells were transfected with plasmids harboring an unspliced renilla luciferase (RLuc) reporter mRNA or RLuc constructs with introns near the 5' or 3' end of the gene. After splicing of intron containing transcripts, all three RLuc mRNAs had the same primary sequence. Upon infection in the presence of actinomycin D, spliced mRNAs were much less sensitive to degradation by copies of Vhs from infecting virions than were unspliced mRNAs. During productive infections (in the absence of drugs), RLuc was expressed at substantially higher levels from spliced than from unspliced mRNAs. Interestingly, the stimulatory effect of splicing on RLuc expression was significantly greater in infected than in uninfected cells. The translational stimulatory effect of an intron during HSV-1 infections could be replicated by artificially tethering various EJC components to an unspliced RLuc transcript. Thus, the splicing history of an mRNA, and the consequent presence or absence of EJCs, affects its level of translation and sensitivity to Vhs cleavage during lytic HSV infections. IMPORTANCE: Most mammalian mRNAs are spliced. In contrast, of the more than 80 mRNAs harbored by herpes simplex virus 1 (HSV-1), only 5 are spliced. In addition, synthesis of the immediate early protein ICP27 causes partial inhibition of pre-mRNA splicing, with the resultant accumulation of both spliced and unspliced versions of some mRNAs in the cytoplasm. A common perception is that HSV-1 infection necessarily inhibits the expression of spliced mRNAs. In contrast, this study demonstrates two instances in which pre-mRNA splicing actually enhances the synthesis of proteins from mRNAs during HSV-1 infections. Specifically, splicing stabilized an mRNA against degradation by copies of the Vhs endoribonuclease from infecting virions and greatly enhanced the amount of protein synthesized from spliced mRNAs at late times after infection. The data suggest that splicing, and the resultant presence of exon junction complexes on an mRNA, may play an important role in gene expression during HSV-1 infections. PMID- 27681128 TI - Bipartite Network Analysis of the Archaeal Virosphere: Evolutionary Connections between Viruses and Capsidless Mobile Elements. AB - : Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses. We constructed a bipartite network of archaeal viruses that includes two classes of nodes, the genomes and gene families that connect them. Dissection of this network using formal community detection methods reveals strong modularity, with 10 distinct modules and 3 putative supermodules. However, compared to similar previously analyzed networks of eukaryotic and bacterial viruses, the archaeal virus network is sparsely connected. With the exception of the tailed viruses related to bacteriophages of the order Caudovirales and the families Turriviridae and Sphaerolipoviridae that are linked to a distinct supermodule of eukaryotic and bacterial viruses, there are few connector genes shared by different archaeal virus modules. In contrast, most of these modules include, in addition to viruses, capsidless mobile elements, emphasizing tight evolutionary connections between the two types of entities in archaea. The relative contributions of distinct evolutionary origins, in particular from nonviral elements, and insufficient sampling to the sparsity of the archaeal virus network remain to be determined by further exploration of the archaeal virosphere. IMPORTANCE: Viruses infecting archaea are among the most mysterious denizens of the virosphere. Many of these viruses display no genetic or even morphological relationship to viruses of bacteria and eukaryotes, raising questions regarding their origins and position in the global virosphere. Analysis of 5,740 protein sequences from 116 genomes allowed dissection of the archaeal virus network and showed that most groups of archaeal viruses are evolutionarily connected to capsidless mobile genetic elements, including various plasmids and transposons. This finding could reflect actual independent origins of the distinct groups of archaeal viruses from different nonviral elements, providing important insights into the emergence and evolution of the archaeal virome. PMID- 27681129 TI - Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice. AB - : Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrPC) and the infecting pathological PrP assemblies (PrPSc) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrPC and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrPSc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross transmission. To address this issue, we compared the biological properties of L BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. IMPORTANCE: Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. PMID- 27681130 TI - Attenuated Infectious Hematopoietic Necrosis Virus with Rearranged Gene Order as Potential Vaccine. AB - : The genome of infectious hematopoietic necrosis virus (IHNV), a salmonid novirhabdovirus, has been engineered to modify the gene order and to evaluate the impact on a possible attenuation of the virus in vitro and in vivo By reverse genetics, eight recombinant IHNVs (rIHNVs), termed NxGy according to the respective positions of the nucleoprotein (N) and glycoprotein (G) genes along the genome, have been recovered. All rIHNVs have been fully characterized in vitro for their cytopathic effects, kinetics of replication, and profiles of viral gene transcription. These rIHNVs are stable through up to 10 passages in cell culture. Following bath immersion administration of the various rIHNVs to juvenile trout, some of the rIHNVs were clearly attenuated (N2G3, N2G4, N3G4, and N4G1). The position of the N gene seems to be one of the most critical features correlated to the level of viral attenuation. The induced immune response potential in fish was evaluated by enzyme-linked immunosorbent spot assay (ELISPOT) and seroneutralization assays. The recombinant virus N2G3 induced a strong antibody response in immunized fish and conferred 86% of protection against wild-type IHNV challenge in trout, thus representing a promising starting point for the development of a live attenuated vaccine candidate. IMPORTANCE: In Europe, no vaccines are available against infectious hematopoietic necrosis virus (IHNV), one of the major economic threats in fish aquaculture. Live attenuated vaccines are conditioned by a sensible balance between attenuation and pathogenicity. Moreover, nonsegmented negative-strain RNA viruses (NNSV) are subject to a transcription gradient dictated by the order of the genes in their genomes. With the perspective of developing a vaccine against IHNV, we engineered various recombinant IHNVs with reordered genomes in order to artificially attenuate the virus. Our results validate the gene rearrangement approach as a potent and stable attenuation strategy for fish novirhabdovirus and open a new perspective for design of vaccines against other NNSV. PMID- 27681131 TI - A Tale of Two PMLs: Elements Regulating a Differential Substrate Recognition by the ICP0 E3 Ubiquitin Ligase of Herpes Simplex Virus 1. AB - : Infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is an alpha gene product required for viral replication at low multiplicities of infection. Upon entry, nuclear domain 10 (ND10) converges at the incoming DNA and represses viral gene expression. ICP0 contains a RING-type E3 ubiquitin ligase that degrades the ND10 organizer PML and disperses ND10 to alleviate the repression. In the present study, we focused on understanding the regulation of ICP0 E3 ligase activity in the degradation of different ICP0 substrates. We report the following. (i) A SUMO interaction motif located at ICP0 residues 362 to 364 is required for the degradation of PML isoforms II, IV, and VI but not isoform I. This differentiation mechanism exists in both HEp-2 and U2OS cells, regardless of the cell's permissiveness to the ICP0-null virus. (ii) Physical interaction between SIM362-364 and PML II is necessary but not sufficient for PML II degradation. Both proximal sequences surrounding SIM362-364 and distal sequences located at the ICP0 C terminus enhance the degradation of PML II. (iii) The ICP0 C terminus is dispensable for PML I degradation. Instead, bipartite PML I binding domains located in the N-terminal half of ICP0 coordinate to promote the degradation of PML I. (iv) The stability of ICP0, but not its ND10 fusion ability, affects the rate of PML I degradation. Taken together, our results show that ICP0 uses at least two regulatory mechanisms to differentiate its substrates. The disparate recognition of the ICP0 E3 substrates may be related to the different roles these substrates may play in HSV-1 infection. IMPORTANCE: Viruses have a limited genetic coding capacity but must encounter a multilayered comprehensive host defense. To establish a successful infection, viruses usually produce multifunctional proteins to coordinate the counteractions. Here we report that an HSV-1 protein, ICP0, can recognize individual host factors and target them differently for destruction. We identified elements that are important for the ICP0 E3 ubiquitin ligase to differentially recognize two of its substrates, PML I and PML II. This is the first study that has systematically investigated how ICP0 discriminates two similar molecules by very different mechanisms. This work lays the foundation for understanding the role of host defensive factors and the mechanisms viruses use to take advantage of some host proteins while destroying others. PMID- 27681134 TI - Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013. AB - : The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio (n = 262) and Indiana (n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans. IMPORTANCE: Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance. PMID- 27681132 TI - Rhinovirus 16 2A Protease Affects Nuclear Localization of 3CD during Infection. AB - : The human rhinovirus (HRV) 3C and 2A proteases (3Cpro and 2Apro, respectively) are critical in HRV infection, as they are required for viral polyprotein processing as well as proteolysing key host factors to facilitate virus replication. Early in infection, 3Cpro is present as its precursor 3CD, which, although the mechanism of subcellular targeting is unknown, is found in the nucleus as well as the cytoplasm. In this study, we use transfected and infected cell systems to show that 2Apro activity is required for 3CD nuclear localization. Using green fluorescent protein (GFP)-tagged forms of 3Cpro, 3D, and mutant derivatives thereof, we show that 3Cpro is located in the cytoplasm and the nucleus, whereas 3CD and 3D are localized predominantly in the cytoplasm, implying that 3D lacks nuclear targeting ability and that 3Cpro activity within 3CD is not sufficient to allow the larger protein into the nucleus. Importantly, by coexpressing mCherry-2Apro fusion proteins, we demonstrate formally that 2Apro activity is required to allow HRV 3CD access to the nucleus. In contrast, mCherry 3Cpro is insufficient to allow 3CD access to the nucleus. Finally, we confirm the relevance of these results to HRV infection by demonstrating that nuclear localization of 3CD correlates with 2Apro activity and not 3Cpro activity, which is observed only later in infection. The results thus define the temporal activities of 2Apro and 3CD/3Cpro activities in HRV serotype16 infection. IMPORTANCE: The human rhinovirus genome encodes two proteases, 2A and 3C, as well as a precursor protease, 3CD. These proteases are essential for efficient virus replication. The 3CD protein is found in the nucleus early during infection, though the mechanism of subcellular localization is unknown. Here we show that 2A protease is required for this localization, the 3C protease activity of 3CD is not sufficient to allow 3CD entry into the nucleus, and 3D lacks nuclear targeting ability. This study demonstrates that both 2A and 3C proteases are required for the correct localization of proteins during infection and defines the temporal regulation of 2A and 3CD/3C protease activities during HRV16 infection. PMID- 27681133 TI - Pathogenesis and Transmission Assessments of Two H7N8 Influenza A Viruses Recently Isolated from Turkey Farms in Indiana Using Mouse and Ferret Models. AB - : Avian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional infections of humans in close contact with affected birds. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low-pathogenic avian influenza (LPAI) viruses was confirmed in commercial turkey farms in Indiana. These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, and their virulence in mammalian hosts and the potential risk for human infection are largely unknown. In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicate in vitro in human airway cells and in vivo in mouse and ferret models. Both H7N8 viruses replicated efficiently in vitro and in vivo, but they exhibited substantial differences in disease severity in mammals. In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact with an inoculated animal, while no transmission of H7N8 HPAI virus was detected. Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health. IMPORTANCE: H7 influenza viruses circulate in wild birds in the United States, but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. An H7N8 highly pathogenic avian influenza (HPAI) virus and an H7N8 low-pathogenic avian influenza (LPAI) virus were recently isolated from commercial turkey farms in Indiana. To determine the risk that these influenza viruses pose to humans, we assessed their pathogenesis and transmission in vitro and in mammalian models. We found that the H7N8 HPAI virus exhibited enhanced virulence, and although transmission was only observed with the H7N8 LPAI virus, the ability of this H7 virus to transmit in a mammalian host and quickly evolve to a more virulent strain is cause for concern. Our findings offer important insight into the potential for emerging H7 avian influenza viruses to acquire the ability to cause disease and transmit among mammals. PMID- 27681135 TI - Reovirus MU1 Protein Affects Infectivity by Altering Virus-Receptor Interactions. AB - : Proteins that form the reovirus outer capsid play an active role in the entry of reovirus into host cells. Among these, the sigma1 protein mediates attachment of reovirus particles to host cells via interaction with cell surface glycans or the proteinaceous receptor junctional adhesion molecule A (JAM-A). The MU1 protein functions to penetrate the host cell membrane to allow delivery of the genome-containing viral core particle into the cytoplasm to initiate viral replication. We demonstrate that a reassortant virus that expresses the M2 gene encoded MU1 protein derived from prototype strain T3D in an otherwise prototype T1L background (T1L/T3DM2) infects cells more efficiently than parental T1L. Unexpectedly, the enhancement in infectivity of T1L/T3DM2 is due to its capacity to attach to cells more efficiently. We present genetic data implicating the central region of MU1 in altering the cell attachment property of reovirus. Our data indicate that the T3D MU1-mediated enhancement in infectivity of T1L is dependent on the function of sigma1 and requires the expression of JAM-A. We also demonstrate that T1L/T3DM2 utilizes JAM-A more efficiently than T1L. These studies revealed a previously unknown relationship between two nonadjacent reovirus outer capsid proteins, sigma1 and MU1. IMPORTANCE: How reovirus attaches to host cells has been extensively characterized. Attachment of reovirus to host cells is mediated by the sigma1 protein, and properties of sigma1 influence the capacity of reovirus to target specific host tissues and produce disease. Here, we present new evidence indicating that the cell attachment properties of sigma1 are influenced by the nature of MU1, a capsid protein that does not physically interact with sigma1. These studies could explain the previously described role for MU1 in influencing reovirus pathogenesis. These studies are also of broader significance because they highlight an example of how genetic reassortment between virus strains could produce phenotypes that are distinct from those of either parent. PMID- 27681136 TI - The Coat Protein and NIa Protease of Two Potyviridae Family Members Independently Confer Superinfection Exclusion. AB - : Superinfection exclusion (SIE) is an antagonistic virus-virus interaction whereby initial infection by one virus prevents subsequent infection by closely related viruses. Although SIE has been described in diverse viruses infecting plants, humans, and animals, its mechanisms, including involvement of specific viral determinants, are just beginning to be elucidated. In this study, SIE determinants encoded by two economically important wheat viruses, Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) and Triticum mosaic virus (TriMV; genus Poacevirus, family Potyviridae), were identified in gain-of function experiments that used heterologous viruses to express individual virus encoded proteins in wheat. Wheat plants infected with TriMV expressing WSMV P1, HC-Pro, P3, 6K1, CI, 6K2, NIa-VPg, or NIb cistrons permitted efficient superinfection by WSMV expressing green fluorescent protein (WSMV-GFP). In contrast, wheat infected with TriMV expressing WSMV NIa-Pro or coat protein (CP) substantially excluded superinfection by WSMV-GFP, suggesting that both of these cistrons are SIE effectors encoded by WSMV. Importantly, SIE is due to functional WSMV NIa-Pro or CP rather than their encoding RNAs, as altering the coded protein products by minimally changing RNA sequences led to abolishment of SIE. Deletion mutagenesis further revealed that elicitation of SIE by NIa-Pro requires the entire protein while CP requires only a 200-amino-acid (aa) middle fragment (aa 101 to 300) of the 349 aa. Strikingly, reciprocal experiments with WSMV-mediated expression of TriMV proteins showed that TriMV CP, and TriMV NIa-Pro to a lesser extent, likewise excluded superinfection by TriMV-GFP. Collectively, these data demonstrate that WSMV- and TriMV-encoded CP and NIa-Pro proteins are effectors of SIE and that these two proteins trigger SIE independently of each other. IMPORTANCE: Superinfection exclusion (SIE) is an antagonistic virus-virus interaction that prevents secondary invasions by identical or closely related viruses in the same host cells. Although known to occur in diverse viruses, SIE remains an enigma in terms of key molecular determinants and action mechanisms. In this study, we found that Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) encode two independently functioning cistrons that serve as effectors of SIE at the protein but not the RNA level. The coat protein and NIa Pro encoded by these two viruses, when expressed from a heterologous virus, exerted SIE to the cognate viruses. The identification of virus-encoded effectors of SIE and their transgenic expression could potentially facilitate the development of virus-resistant crop plants. Additionally, functional conservation of SIE in diverse virus groups suggests that a better understanding of the underlying mechanisms of SIE could facilitate the development of novel antiviral therapies against viral diseases. PMID- 27681137 TI - Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells. AB - : Tat protein, the HIV transactivator, regulates transcription of the HIV genome by the host transcription machinery. Efficient inhibitors of HIV transcription that target Tat or the cellular cofactor NF-kappaB are well known. However, inhibition of HIV Tat-dependent transcription by targeting the general transcription and DNA repair factor II human (TFIIH) has not been reported. Here, we show that spironolactone (SP), an aldosterone antagonist approved for clinical use, inhibits HIV-1 and HIV-2 infection of permissive T cells by blocking viral Tat-dependent transcription from the long terminal repeat (LTR). We found that treatment of Jurkat and primary CD4+ T cells with SP induces degradation of the XPB cellular helicase, a component of the TFIIH complex, without affecting cellular mRNA levels, T cell viability, or T cell proliferation. We further demonstrate that the effect of SP on HIV infection is independent of its aldosterone antagonist function, since the structural analogue, eplerenone, does not induce XPB degradation and does not inhibit HIV infection. Rescue experiments showed that the SP-induced block of HIV infection relies, at least partially, on XPB degradation. In addition, we demonstrate that SP specifically inhibits Tat dependent transcription, since basal transcription from the LTR is not affected. Our results demonstrate that SP is a specific inhibitor of HIV Tat-dependent transcription in T cells, which additionally suggests that XPB is a cofactor required for HIV infection. Targeting a cellular cofactor of HIV transcription constitutes an alternative strategy to inhibit HIV infection, together with the existing antiretroviral therapy. IMPORTANCE: Transcription from the HIV promoter is regulated by the combined activities of the host transcription machinery and the viral transactivator Tat protein. Here, we report that the drug spironolactone-an antagonist of aldosterone-blocks viral Tat-dependent transcription, thereby inhibiting both HIV-1 and HIV-2 infection of permissive T cells. This inhibition relies on the degradation of the cellular helicase XPB, a component of the TFIIH transcription factor complex. Consequently, XPB appears to be a novel HIV cofactor. Our discovery of the HIV-inhibitory activity of spironolactone opens the way for the development of novel anti-HIV strategies targeting a cellular cofactor without the limitations of antiretroviral therapy of drug resistance and high cost. PMID- 27681138 TI - Herpes Simplex Virus 1 Tegument Protein UL41 Counteracts IFIT3 Antiviral Innate Immunity. AB - : The interferon-induced protein with tetratricopeptide repeat 3 (IFIT3 or ISG60) is a host-intrinsic antiviral factor that restricts many instances of DNA and RNA virus replication. Herpes simplex virus 1 (HSV-1), a DNA virus bearing a large genome, can encode many viral proteins to counteract the host immune responses. However, whether IFIT3 plays a role upon HSV-1 infection is little known. In this study, we show for the first time that HSV-1 tegument protein UL41, a viral endoribonuclease, plays an important role in inhibiting the antiviral activity of IFIT3. Here, we demonstrated that ectopically expressed IFIT3 could restrict the replication of vesicular stomatitis virus (VSV) but had little effect on the replication of wild-type (WT) HSV-1. Further study showed that WT HSV-1 infection downregulated the expression of IFIT3, and ectopic expression of UL41, but not the immediate-early protein ICP0, notably reduced the expression of IFIT3. The underlying molecular mechanism was that UL41 diminished the accumulation of IFIT3 mRNA to abrogate its antiviral activity. In addition, our results illustrated that ectopic expression of IFIT3 inhibited the replication of UL41-null mutant virus (R2621), and stable knockdown of IFIT3 facilitated its replication. Taking these findings together, HSV-1 was shown for the first time to evade the antiviral function of IFIT3 via UL41. IMPORTANCE: The tegument protein UL41 of HSV-1 is an endoribonuclease with the substrate specificity of RNase A, which plays an important role in viral infection. Upon HSV-1 infection, interferons are critical cytokines that regulate immune responses against viral infection. Host antiviral responses are significantly boosted or crippled in the presence or absence of IFIT3; however, whether IFIT3 plays a role during HSV-1 infection is still unknown. Our data show for the first time that IFIT3 has little effect on HSV-1 replication, as UL41 decreases the accumulation of IFIT3 mRNA and subverts its antiviral activity. This study identifies IFIT3 as a novel target of the tegument protein UL41 and provides new insight into HSV-1-mediated immune evasion. PMID- 27681139 TI - The US3 Protein of Pseudorabies Virus Drives Viral Passage across the Basement Membrane in Porcine Respiratory Mucosa Explants. AB - : Passage of the basement membrane (BM), which forms a barrier between the epithelium and the underlying lamina propria, represents an important step in the early pathogenesis of different alphaherpesviruses. Rho GTPase signaling plays an important role in transmigration of cells across the BM during physiological and pathological processes. We reported earlier that the US3 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) interferes with Rho GTPase signaling and causes a reorganization of the host cell cytoskeleton, which as a consequence, enhances viral cell-to-cell spread in epithelial cell cultures. Here, using an ex vivo system of porcine nasal respiratory mucosa explants that allows to study PRV invasion through the BM, we found that a PRV strain that lacks US3 expression (DeltaUS3 PRV) showed a reduced spread in mucosal epithelium and was virtually unable to breach the BM, in contrast to isogenic wild-type (WT) or US3 rescue PRV strains. Interestingly, addition of IPA3, an inhibitor of p21 activated kinases that blocks the effects of US3 on the cytoskeleton, suppressed the ability of WT PRV to spread across the BM. In addition, artificial suppression of RhoA signaling using CPC3 (cell-permeable C3 transferase) to mimic the effects of US3 on Rho GTPase signaling, significantly increased passage of DeltaUS3 PRV through the BM, whereas it did not significantly affect BM passage of WT or US3 rescue PRV. In conclusion, these data indicate that US3 plays an important role in PRV mucosal invasion across the BM, which involves its interference with Rho GTPase signaling. This is the first report describing an alphaherpesvirus protein that drives viral BM passage. IMPORTANCE: Many viruses, including alphaherpesviruses, primarily replicate in epithelial cells of surface mucosae, such as the respiratory mucosa. Some of these viruses breach the basement membrane underlying these epithelial cells to reach underlying connective tissue and blood vessels and invade the host. Hence, epithelial spread and basement membrane passage represent crucial but still poorly understood early steps in (alphaherpes)virus pathogenesis. Here, using ex vivo porcine respiratory mucosa explants, we show that the conserved US3 protein of the porcine alphaherpesvirus pseudorabies virus (PRV) is critical for passage of PRV across the basement membrane and contributes to efficient viral epithelial spread. In addition, we show that US3-mediated viral epithelial spread and passage across the basement membrane depend at least in part on the ability of this viral protein to modulate cellular Rho GTPase signaling. This is the first report that identifies an alphaherpesvirus protein that drives viral basement membrane passage. PMID- 27681141 TI - Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates. AB - : Although HIV-2 does not encode a vpu gene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu like activity to an inactive Env variant. Surprisingly, however, absence of Vpu like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit. IMPORTANCE: Lentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode a vpu gene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence. PMID- 27681140 TI - The Antagonism of HIV-1 Nef to SERINC5 Particle Infectivity Restriction Involves the Counteraction of Virion-Associated Pools of the Restriction Factor. AB - : SERINC3 (serine incorporator 3) and SERINC5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred in parallel with other Nef activities, including cell surface receptor downregulation, trans-Golgi network targeting of Lck, and inhibition of host cell actin dynamics. Interaction motifs with host cell endocytic machinery and the Nef associated kinase complex, as well as CD4 cytoplasmic tail/HIV-1 protease, were identified as essential Nef determinants for SERINC5 antagonism. Characterization of antagonism-deficient Nef mutants revealed that counteraction of SERINC5 occurs in the absence of retargeting of the restriction factor to intracellular compartments and reduction of SERINC5 cell surface density is insufficient for antagonism. Consistent with virion incorporation of SERINC5 being a prerequisite for its antiviral activity, the infectivity of HIV-1 particles produced in the absence of a SERINC5 antagonist decreased with increasing amounts of virion SERINC5. At low levels of SERINC5 expression, enhancement of virion infectivity by Nef was associated with reduced virion incorporation of SERINC5 and antagonism defective Nef mutants failed to exclude SERINC5 from virions. However, at elevated levels of SERINC5 expression, Nef maintained infectious HIV particles, despite significant virion incorporation of the restriction factor. These results suggest that in addition to virion exclusion, Nef employs a cryptic mechanism to antagonize virion-associated SERINC5. The involvement of common determinants suggests that the antagonism of Nef to SERINC5 and the downregulation of cell surface CD4 by Nef involve related molecular mechanisms. IMPORTANCE: HIV-1 Nef critically determines virus spread and disease progression in infected individuals by incompletely defined mechanisms. SERINC3 and SERINC5 were recently identified as potent inhibitors of HIV particle infectivity whose antiviral activity is antagonized by HIV-1 Nef. To address the mechanism of SERINC5 antagonism, we identified four molecular determinants of Nef antagonism that are all linked to the mechanism by which Nef downregulates cell surface CD4. Functional characterization of these mutants revealed that endosomal targeting and cell surface downregulation of SERINC5 are dispensable and insufficient for antagonism, respectively. In contrast, virion exclusion and antagonism of SERINC5 were correlated; however, Nef was also able to enhance the infectivity of virions that incorporated robust levels of SERINC5. These results suggest that the antagonism of HIV-1 Nef to SERINC5 restriction of virion infectivity is mediated by a dual mechanism that is related to CD4 downregulation. PMID- 27681144 TI - Antiretroviral adherence and virological outcomes in HIV-positive patients in Ugu district, KwaZulu-Natal province. AB - Adherence to antiretroviral therapy is crucial to ensure viral suppression. In the scientific community it is widely accepted that an adherence level of at least 90% is necessary to achieve viral suppression. This study uses pharmacy refill records to describe antiretroviral adherence in HIV-positive patients in Ugu District, KwaZulu-Natal, South Africa and to describe pharmacy refill records as reliable monitoring method of antiretroviral therapy. In total, 61 patients' records were reviewed. Overall, 50 (82%) of the patients achieved an optimum adherence level of at least 90%, whereas 19 (38%) of these patients did not show any related viral suppression. A statistically significant relationship between adherence and viral suppression was not demonstrated. Therefore, pharmacy refill records cannot be recommended as an alternative method of monitoring response to antiretroviral therapy, but laboratory tests including CD4 cell count and or viral load must be combined with the pharmacy refill method for monitoring of antiretroviral therapy in HIV-positive patients. PMID- 27681142 TI - TRIM5alpha Resistance Escape Mutations in the Capsid Are Transferable between Simian Immunodeficiency Virus Strains. AB - : TRIM5alpha polymorphism limits and complicates the use of simian immunodeficiency virus (SIV) for evaluation of human immunodeficiency virus (HIV) vaccine strategies in rhesus macaques. We previously reported that the TRIM5alpha sensitive SIV from sooty mangabeys (SIVsm) clone SIVsmE543-3 acquired amino acid substitutions in the capsid that overcame TRIM5alpha restriction when it was passaged in rhesus macaques expressing restrictive TRIM5alpha alleles. Here we generated TRIM5alpha-resistant clones of the related SIVsmE660 strain without animal passage by introducing the same amino acid capsid substitutions. We evaluated one of the variants in rhesus macaques expressing permissive and restrictive TRIM5alpha alleles. The SIVsmE660 variant infected and replicated in macaques with restrictive TRIM5alpha genotypes as efficiently as in macaques with permissive TRIM5alpha genotypes. These results demonstrated that mutations in the SIV capsid can confer SIV resistance to TRIM5alpha restriction without animal passage, suggesting an applicable method to generate more diverse SIV strains for HIV vaccine studies. IMPORTANCE: Many strains of SIV from sooty mangabey monkeys are susceptible to resistance by common rhesus macaque TRIM5alpha alleles and result in reduced virus acquisition and replication in macaques that express these restrictive alleles. We previously observed that spontaneous variations in the capsid gene were associated with improved replication in macaques, and the introduction of two amino acid changes in the capsid transfers this improved replication to the parent clone. In the present study, we introduced these mutations into a related but distinct strain of SIV that is commonly used for challenge studies for vaccine trials. These mutations also improved the replication of this strain in macaques with the restrictive TRIM5alpha genotype and thus will eliminate the confounding effects of TRIM5alpha in vaccine studies. PMID- 27681143 TI - Genetic Determinants of Clozapine-Induced Metabolic Side Effects. AB - OBJECTIVE: Atypical antipychotics are linked to a higher incidence of metabolic side effects, including weight gain, dyslipidemia, and diabetes. In this study, we examined the prevalence and potential genetic predictors of metabolic side effects in 60 adult patients on clozapine. METHOD: Genetic variants of relevance to clozapine metabolism, clearance, and response were assessed through targeted genotyping of cytochrome P450 enzymes CYP1A2 and CYP2C19, the efflux transporter ABCB1, the serotonin receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR). Clozapine levels and other potential confounders, including concurrent medications, were also included in the analysis. RESULTS: More than half of the patients were obese (51%), had metabolic syndrome (52.5%), and 30.5% were overweight. There was a high prevalence of antipsychotic polypharmacy (61.9%). With multivariable linear regression analysis, LEP -2548G>A, LEPR c.668A>G, and HTR2C c.551-3008 C>G were identified as genetic predictors of body mass index (BMI) after considering effects of clozapine dose, blood level, and concurrent medications (adjusted R2 = 0.305). Metabolic syndrome was found to be significantly associated with clozapine level and CYP2C19*2 and LEPR c.668 G alleles. Clozapine levels in patients with metabolic syndrome were significantly higher compared to those without metabolic syndrome (1886 +/- 895 vs. 1283 +/- 985 ng/mL, P < 0.01) and were associated with the CYP2C19*2 genotype. No association was found between the genetic variants studied and lipid or glucose levels. CONCLUSION: This study confirms a high prevalence of metabolic side effects with clozapine and suggests higher clozapine level and pharmacogenetic markers in CYP2C19, LEP, LEPR, and HTR2C receptors as important predictors of BMI and metabolic syndrome. PMID- 27681146 TI - Clinical correlates of suicidality among individuals with HIV infection and AIDS disease in Mbarara, Uganda. AB - The association between suicidality and HIV/AIDS has been demonstrated for three decades, but little is know about risk factors that can help understand this association and help identify who is most at risk. Few research studies have been conducted in sub-Saharan Africa, a region that accounts for more than 70% of the HIV global burden. This paper describes clinical risk factors for suicidality among individuals with HIV infection and AIDS disease in Mbarara, Uganda. In this study, suicidality includes both suicidal ideation and suicidal attempts. A cross sectional survey was conducted with 543 HIV-positive individuals aged 15 years and above, recruited from 2 HIV specialised clinics in Mbarara. Using logistic regression analysis, factors significantly associated with suicidality at 95% confidence interval were identified. The rate of suicidality was 10% (n = 54; 95% CI: 5.00-15.00). Risk factors for suicidality were: perception of poor physical health (OR 2.22, 95% CI 1.23-3.99, p = 0.007), physical pain (OR 1.83, 95% CI 1.01-3.30, p = 0.049), reducing work due to illness (OR = 2.22, 95% CI 1.23-3.99, p = 0.004) and recent HIV diagnosis (OR 1.02, 95% CI 1.01-1.03, p = 0.001). These findings suggest that HIV/AIDS in south-western Uganda is associated with a considerable burden of suicidality. HIV is associated with several clinical factors that increase vulnerability to suicidality. There is need for more appropriate interventions targeting these clinical risk factors, systematic suicide risk assessment and management of suicidal ideation and behaviours in HIV care. PMID- 27681145 TI - A qualitative study of migrant-related stressors, psychosocial outcomes and HIV risk behaviour among truck drivers in Zambia. AB - Truck drivers are part of mobile populations which have been noted as a key population at risk of HIV in Zambia. This study was aimed at: (1) determining potentially traumatic events (PTEs), labour migrant-related stressors, psychosocial problems and HIV risk behaviours among truck drivers in Zambia; and (2) examining the relationship between PTEs, migrant-related stressors, psychosocial outcomes and HIV sexual risk behaviour among truck drivers in Zambia. We conducted 15 semi-structured interviews with purposively sampled male truck drivers at trucking companies in Lusaka, Zambia. Findings indicate that truck drivers experience multiple stressors and potentially traumatic incidences, including delays and long waiting hours at borders, exposure to crime and violence, poverty, stress related to resisting temptation of sexual interactions with sex workers or migrant women, and job-related safety concerns. Multiple psychosocial problems such as intimate partner violence, loneliness, anxiety and depression-like symptoms were noted. Transactional sex, coupled with inconsistent condom use, were identified as HIV sexual risk behaviours. Findings suggest the critical need to develop HIV-prevention interventions which account for mobility, potentially traumatic events, psychosocial problems, and the extreme fear of HIV testing among this key population. PMID- 27681147 TI - Teachers' subjectivities and emotionality in HIV/AIDS teaching. AB - Schools play a significant role in conveying essential knowledge, skills and attitudes about HIV and AIDS to millions of learners, and are therefore at the forefront of addressing the HIV/AIDS pandemic. This has resulted in a shift in HIV/AIDS research to focus on the crucial role of teachers in HIV prevention. This paper explores the influence of teachers' subjectivities and emotionality on their teaching about HIV/AIDS. The paper draws on qualitative, narrative data gathered from five teachers teaching in a midlands town in KwaZulu-Natal, South Africa. It finds that teachers' subject positions play a significant role in presenting compassionate, supportive and knowledgeable subjectivities in the classroom; and that their positive and negative emotions pivotally influence their teaching about HIV/AIDS. We argue that it is vital to consider how teachers position themselves, as this is intricately linked with their teaching about HIV/AIDS, and we draw attention to teaching about HIV/AIDS as an emotional practice. PMID- 27681149 TI - Leadership emergence: the application of the Cynefin framework during a bio social HIV/AIDS risk-reduction pilot. AB - This article focuses on the utility of a knowledge management heuristic called the Cynefin framework, which was applied during an ongoing pilot intervention in the Limpopo province, South Africa. The intervention aimed to identify and then consolidate low-cost, innovative bio-social responses to reinforce the biomedical opportunities that now have the potential to "end AIDS by 2030". The Cynefin framework is designed to enable leaders to identify specific decision-making domain typologies as a mechanism to maximise the effectiveness of leadership responses to both opportunities and challenges that emerge during interventions. In this instance the Cynefin framework was used to: (1) provide an indication to the project managers whether the early stages of the intervention had been effective; (2) provide the participants an opportunity to identify emergent knowledge action spaces (opportunities and challenges); and (3) categorise them into appropriate decision-making domains in preparation for the next phases of the intervention. A qualitative methodology was applied to collect and analyse the findings. The findings indicate that applying the Cynefin framework enabled the participants to situate knowledge action spaces into appropriate decision making domains. From this participatory evaluation a targeted management strategy was developed for the next phases of the initiative. The article concludes by arguing that the Cynefin framework was an effective mechanism for situating emergent knowledge action spaces into appropriate decision-making domains, which enabled them to prepare for the next phases of the intervention. This process of responsive decision making could have utility in other development related interventions. PMID- 27681148 TI - Adverse drug reactions associated with antiretroviral therapy in South Africa. AB - South Africa has one of the highest prevalences of HIV and AIDS in the world. HIV/AIDS patients face countless challenges, one of which is the risk of adverse drug reactions (ADRs). This study aimed to describe the ADRs reported in South Africa with reference to the type of ADRs, antiretrovirals (ARVs) implicated, seriousness of the ADRs and patient demographics associated with specific ADRs. A retrospective quantitative study was carried out using ADR reports submitted to the National Department of Health (NDoH) from 1 January 2010 to 31 December 2014. A descriptive and inferential analysis was carried out to determine the strength of the relationships between different variables. A total of 2 489 reports were analysed. This study found evidence of ADRs among patients on regimens based on stavudine (n = 1 256, 50.46%), efavirenz (n = 572, 22.98%), zidovudine (n = 209, 8.40%), tenofovir (n = 203, 8.16%) and nevirapine (n = 153, 6.15%). The 10 most common ADRs reported with the use of ARVs were peripheral neuropathy (n = 472, 19%), lipodystrophy (n = 471, 18.9%), serious skin reactions (n = 266, 10.7%), gynaecomastia (n = 219, 8.8%), renal failure (n = 140, 5.6%), dizziness (n = 133, 5.3%), hyperlactatemia (n = 118, 4.7%), psychosis/hallucinations (n = 47, 1.9%), sleep disturbances (n = 44, 1.8%) and vomiting (n = 44, 1.8%). Female patients were more likely to experience peripheral neuropathy, lipodystrophy, skin rash, anaemia and hyperlactatemia, while male patients were more prone to experience gynaecomastia and peripheral neuropathy. In addition, patients aged 30-44 years reported the most ADRs. Most reactions resulted from the use of stavudine, efavirenz, zidovudine, nevirapine and tenofovir in the population groups identified in this study. PMID- 27681150 TI - Psychosocial well-being of people living with HIV and the community before and after a HIV stigma-reduction community "hub" network intervention. AB - The purpose of the research was to determine whether an HIV stigma-reduction community "hub" network intervention in a South African urban area would bring about a difference in the psychosocial well-being of people living with HIV (PLWH), as well as their community (living in the same municipal ward). A single case pre-test post-test design was implemented. The sample for this study included 62 PLWH who were selected through accessibility sampling and 570 community members who were selected through random voluntary sampling. Participants completed the Patient Health Questionnaire (PHQ-9) and the Mental Health Continuum-Short Form (MHC-SF) before and after the intervention. A dependent t-test as well as Cohen's d-values were used to calculate the differences between the pre- and post-test results for depression and well-being. Levels of languishing, moderate mental health and flourishing before and after the intervention were determined. Although the focus of the HIV stigma-reduction community "hub" intervention that was followed in this study was on the involvement of PLWH and people living close to them (PLC) to share their knowledge as community mobilisers and to mobilise and empower their own community to reduce HIV stigma, it can be concluded that a secondary gain was the effect it had on both depression and mental health of the PLWH as well as the community. Of interest is how these effects differed for PLWH and the community. It is thus recommended that future interventions should give special attention to aspects of depression and well-being. PMID- 27681151 TI - Church representatives' perspectives on masculinities in the context of HIV: the case of the Ecumenical HIV and AIDS Initiative in Africa. AB - Despite a growing body of literature related to church leaders challenging dominant norms of masculinities that may enable the spread of HIV, research on masculinity issues among African church representatives who are policy makers is scarce. The objectives of this study were to explore the perspectives on masculinities held by church representatives within the Ecumenical HIV and AIDS Initiative in Africa (EHAIA) and to identify strategies they used to transform masculinities in their respective churches. Qualitative interviews were carried out with 14 church representatives belonging to the EHAIA International Reference Group. These interviews were analysed using thematic analysis and four themes were identified: "barriers to challenge masculinities" may contribute to the spread of HIV; "counterproductive conservative church leadership" fails to challenge dominant forms of masculinities; "facilitators to challenge masculinities" perceived as slowly changing men and "an evolving hope for gender equality" would be perceived in certain marital relationships. The latter two were viewed as positive approaches resulting from masculinity workshops and male priests disclosing their HIV-positive status. This research highlights strategies that may help male church-goers challenge masculinities, support gender equality and, improve the lives of men and women in the context of HIV. PMID- 27681152 TI - Morbidity and nutrition status of rural drug-naive Kenyan women living with HIV. AB - This paper describes morbidity in a group of HIV-positive drug-naive rural women in western Kenya. A total of 226 drug-naive HIV-positive women were evaluated for baseline morbidity, immune function, and anthropometry before a food-based nutrition intervention. Kenyan nurses visited women in their homes and conducted semi-structured interviews regarding symptoms and physical signs experienced at the time of the visit and during the previous week and physical inspection. Blood and urine samples were examined for determination of immune function (CD4, CD8, and total lymphocyte counts), anaemia, malaria, and pregnancy status. Intradermal skin testing with tuberculin (PPD), candida, and tetanus toxoid antigens was also performed to evaluate cell-mediated immunity. Anthropometry was measured, and body mass index (BMI) was calculated. Seventy-six per cent of the women reported being sick on the day of the interview or within the previous week. Illnesses considered serious were reported by 13.7% of women. The most frequent morbidity episodes reported were upper respiratory tract infections (13.3%), suspected malaria (5.85%), skeletal pain (4.87%), and stomach pain (4.42%). The most common morbidity signs on physical inspection were respiratory symptoms, most commonly rhinorrhea and coughing. Confirmed malaria and severe diarrhea were significantly associated with a higher BMI. PMID- 27681153 TI - Political economy of decentralising HIV and AIDS treatment services to primary healthcare facilities in three Nigerian states. AB - Decentralisation is defined as the dispersion, distribution or transfer of resources, functions and decision-making power from a central authority to regional and local authorities. It is usually accompanied by assignment of accountability and responsibility for results. Fundamental to understanding decentralisation is learning what motivates central governments to give up power and resources to local governments, and the practical significance of this on their positions regarding decentralisation. This study examined key political and institutional influences on role-players' capacity to support decentralisation of HIV and AIDS treatment services to primary healthcare facilities, and implications for sustainability. In-depth interviews were conducted with 55 purposively selected key informants, drawn from three Nigerian states that were at different stages of decentralising HIV and AIDS treatment services to primary care facilities. Key informants represented different categories of role-players involved in HIV and AIDS control programmes. Thematic framework analysis of data was done. Support for decentralisation of HIV and AIDS treatment services to primary healthcare facilities was substantial among different categories of actors. Political factors such as the local and global agenda for health, political tenure and party affiliations, and institutional factors such as consolidation of decision-making power and improvements in career trajectories, influenced role-players support for decentralisation of HIV and AIDS treatment services. It is feasible and acceptable to decentralise HIV and AIDS treatment services to primary healthcare facilities, to help improve coverage. However, role-players' support largely depends on how well the reform aligns with political structures and current institutional practices. PMID- 27681155 TI - Social sustainability as the seventh tenant: a reflection on Oberth and Whiteside's sustainability in the HIV and AIDS response. PMID- 27681154 TI - Keeping kids in care: virological failure in a paediatric antiretroviral clinic and suggestions for improving treatment outcomes. AB - The burden of paediatric HIV in South Africa is extremely high. Antiretrovirals (ARVs) are now widely accessible in the country and the clinical emphasis has shifted from initiation of treatment to retention in care. This study describes the cumulative virological failure rate amongst children on ARVs in a peri-urban clinic, and suggests ways in which clinics and partners could improve treatment outcomes. The study was conducted by the non-profit organisation HOPE Cape Town Association. A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all children with a viral load >1000 copies/ml, children on monotherapy, children who had stopped treatment, children lost to follow-up (LTFU) and children who had died. Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care. Cumulative virological failure rate was 42%, with most of those children having been LTFU. Both staff and caregivers consistently identified pharmacy queues, ongoing stigma and unpalatable ARVs as barriers to adherence. Staff suggestions included use of adherence aids, and better education and support groups for caregivers. Caregivers also requested support groups, as well as "same day" appointments for caregivers and children, but rejected the idea of home visits. Simple, acceptable and cost-effective strategies exist whereby clinics and their partners could significantly reduce the cumulative virological failure rate in paediatric ARV clinics. These include actively tracing defaulters, improving education, providing support groups, and campaigning for palatable ARV formulations. PMID- 27681156 TI - Sleep problems and dissociation in preschool victims of sexual abuse. AB - OBJECTIVE: Child sexual abuse (CSA) is associated with a host of deleterious impacts, yet little is known about the short-term correlates in children. This study aimed to investigate the association between dissociation and sleep problems in a sample of preschool-age sexual abuse victims while controlling for potentially confounding variables, including gender, age, polytrauma, CSA characteristics, and parental distress. METHOD: The sample consisted of 179 children (ages 3-6 years) and their non-offending parents. Parents completed questionnaires assessing their child's dissociative symptoms and sleep problems as well as their own level of psychological distress. RESULTS: Regression analyses revealed that sleep problems were significantly associated with dissociative symptoms over and above all other control variables (children's gender and age, polytrauma, and parental distress). A longer duration of sexual abuse also predicted greater dissociative symptoms in preschool children. CONCLUSION: Findings highlight the association between sleep problems and dissociation in preschool-age victims of CSA. Further research is needed to understand their impact on children's development to design appropriate treatment and prevention initiatives aimed at fostering resilience in young vulnerable children. PMID- 27681157 TI - Erratum: Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma. PMID- 27681158 TI - Tissue Selective Androgen Receptor Modulators (SARMs) Increase Pelvic Floor Muscle Mass in Ovariectomized Mice. AB - Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including selective androgen receptor modulators (SARMs) may serve as therapeutic options for individuals with SUI. In this study, two SARMs (GTx-024 and GTx-027) were evaluated in a post-menopausal animal model in order to determine their effect on pelvic floor muscles. Female C57BL/6 mice were ovariectomized and their pelvic muscles allowed to regress. The animals were then treated with vehicle or doses of GTx-024 or GTx-027. Animal total body weight, lean body mass, and pelvic floor muscle weights were measured along with the expression of genes associated with muscle catabolism. Treatment with the SARMs resulted in a restoration of the pelvic muscles to the sham-operated weight. Coordinately, the induction of genes associated with muscle catabolism was inhibited. Although a trend was observed towards an increase in total lean body mass in the SARM-treated groups, no significant differences were detected. Treatment of an ovariectomized mouse model with SARMs resulted in an increase in pelvic floor muscles, which may translate to an improvement of symptoms associated with SUI and serves as the basis for evaluating their clinical use. J. Cell. Biochem. 118: 640-646, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27681160 TI - Endoscopic ultrasonography-guided choledochoduodenostomy using a newly designed laser-cut metal stent: Feasibility study in a porcine model. AB - BACKGROUND AND AIM: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (EUS-CDS) is increasingly used in the treatment of malignant distal biliary obstruction. Standardized use of this technique requires improvements in instruments, including more convenient and safer devices. The present study was designed to evaluate the resistance force to migration (RFM) of a newly designed laser-cut metal stent and the feasibility of EUS-CDS using this stent. METHODS: This experimental study used a porcine model of biliary dilatation involving five male pigs. The new stent is a fully covered laser-cut stent with anti-migration anchoring hooks. The RFM of the new stents was compared with those of three commercially available covered metal stents using a phantom model. In the animal study, after ligation of Vater's ampulla with endoscopic clips, the dilated common bile duct was punctured under EUS guidance, followed by EUS-CDS using the new stent. One week after the procedure, the stents were removed endoscopically and the fistulas were assessed after the pigs were killed. Technical feasibility and clinical outcomes were evaluated. RESULTS: Among the four stents, the new stent had the highest RFM. Metal stent placement was successful in all five pigs, with no procedure-related complications occurring during and 1 week after endoscopic intervention. All stents remained in place without migration and were removed easily using a snare. At necropsy, fistulas were created between the bile duct and duodenum in all pigs. CONCLUSION: EUS-CDS using a newly designed metal stent was feasible and effective in this porcine model of biliary dilatation. PMID- 27681159 TI - Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy. AB - Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID- 27681161 TI - Knowledge extraction from a nitrification denitrification wastewater treatment plant using SOM-NG algorithm. AB - SOM-NG is a hybrid algorithm that is able to carry out visualization of process data, nonlinear function approximation, classification and clustering. The supervised version of SOM-NG produces a new type of 2D lattices called gradient planes which are useful to determine the dynamics of a target variable according to the remaining training variables. In this way, it is an interesting tool for data mining in order to extract knowledge from databases for nonlinear systems. The main objective of this work is to analyze data from an industrial wastewater treatment plant using SOM-NG algorithm in order to investigate relationships between the process variables. The data used proceeds from a biological wastewater treatment plant. This plant is based on an activated sludge treatment including nitrification and denitrification processes. A direct relation between the nitrification efficiency and the operating temperature was found, and also between the ammonia loading rate and the nitrification denitrification efficiency. PMID- 27681162 TI - The backtracking search optimization algorithm for frequency band and time segment selection in motor imagery-based brain-computer interfaces. AB - Common spatial pattern (CSP) is a powerful algorithm for extracting discriminative brain patterns in motor imagery-based brain-computer interfaces (BCIs). However, its performance depends largely on the subject-specific frequency band and time segment. Accurate selection of most responsive frequency band and time segment remains a crucial problem. A novel evolutionary algorithm, the backtracking search optimization algorithm is used to find the optimal frequency band and the optimal combination of frequency band and time segment. The former is searched by a frequency window with changing width of which starting and ending points are selected by the backtracking optimization algorithm; the latter is searched by the same frequency window and an additional time window with fixed width. The three parameters, the starting and ending points of frequency window and the starting point of time window, are jointly optimized by the backtracking search optimization algorithm. Based on the chosen frequency band and fixed or chosen time segment, the same feature extraction is conducted by CSP and subsequent classification is carried out by Fisher discriminant analysis. The classification error rate is used as the objective function of the backtracking search optimization algorithm. The two methods, named BSA-F CSP and BSA-FT CSP, were evaluated on data set of BCI competition and compared with traditional wideband (8-30[Formula: see text]Hz) CSP. The classification results showed that backtracking search optimization algorithm can find much effective frequency band for EEG preprocessing compared to traditional broadband, substantially enhancing CSP performance in terms of classification accuracy. On the other hand, the backtracking search optimization algorithm for joint selection of frequency band and time segment can find their optimal combination, and thus can further improve classification rates. PMID- 27681163 TI - Molecular Characterization and Viral Origin of the 2015 Dengue Outbreak in Xishuangbanna, Yunnan, China. AB - A total of 1067 serum samples were collected from febrile patients in Xishuangbanna, Yunnan, 2015. Of these, 852 cases were confirmed to be dengue NS1 positive. 76 structural protein genes were sequenced through RT-PCR based on the viral RNAs extracted from serum samples. Phylogenetic analysis revealed that all strains were classified as cosmopolitan genotype of DENV-2. After comparing with the DENV-2SS, 173 base substitutions were found in 76 sequences, resulting in 43 nonsynonymous mutations, of which 22 mutations existed among all samples. According to secondary structure prediction, 8 new possible nucelotide/protein binding sites were found and another 4 sites were lost among the 775 amino acids of DENV structural proteins as compared with DENV-2SS. Meanwhile, 6 distinct amino acid changes were found in the helix and strand regions, and the distribution of the exposed and buried regions was slightly altered. The results indicated that the epidemic dengue strains of Xishuangbanna in 2015 are most similar to the Indian strain in 2001 and the Sri Lankan strain in 2004. Moreover, it also show a very strong similarity to the epidemic strains of Fujian province in 1999 and 2010, which show that there is an internal recycling epidemic trend of DENV in China. PMID- 27681164 TI - Influence of time and different tooth widths on masticatory efficiency and muscular activity in bilateral free-end saddles. AB - PURPOSE: To evaluate the influence of time on masticatory efficiency and muscular activity during mastication of different types of test foods in participants fitted with a lower bilateral free-end saddle removable partial denture (RPD) with wide or narrow teeth. METHODS: Thirty-six participants consented to undergo evaluation of their masticatory efficiency and recording of their muscular activity, while they wore an RPD with a unified bilateral design, during mastication of different types of test foods. The width of the artificial teeth was changed as follows. Initially (A), the length was adjusted so that the distal end of the mandibular second molars occluded with the distal end of the maxillary second molar (buccolingual width of 7-8 mm). Next (B), the width was decreased to half the maxillary second molars (buccolingual width of only 5 mm). A statistical analysis was performed using SAS software. One-way analysis of variance (ANOVA) was performed followed by Duncan's multiple range tests. RESULTS: At the 2-month follow-up visit, wider teeth demonstrated greater masticatory efficiency than narrower teeth. However, after 4 months, no significant differences were observed between the two tooth widths. No significant differences in muscular activity were observed. CONCLUSION: A reduction of the occlusal table width in free-end saddle RPDs resulted in decreased masticatory efficiency 2 months after denture fabrication, but there was no significant difference in muscular activity between narrow and wide teeth. However, after 4 months, the masticatory efficiency of the participants with narrower teeth improved without any changes in muscular activity. PMID- 27681165 TI - Survival of Probiotics in Hypromellose Capsules with Rice or Potato Maltodextrin Excipient. AB - There is currently no authorized or established therapeutic level/dose of probiotics for proposed health benefits; however, a daily probiotic consumption of 108 to 1010 CFU has been recommended. This study determined the survival of 5 individual probiotic strains, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus acidophilus, and Bifidobacterium lactis, along with a mixture of the 5 strains in hypromellose capsules with rice or potato maltodextrin at 4, 25, and 37 degrees C for 12 mo. Samples were collected monthly and plated on deMan-Rogosa Sharpe agar with 0.05% l-cysteine hydrochloride. Results showed that samples stored at 4 degrees C had an average count of 108 to 1011 CFU/g of probiotic cells during the 12 mo period, whereas at 25 degrees C, L. rhamnosus and L. paracasei had an average counts below 108 CFU/g during the storage period. L. rhamnosus was the most vulnerable strain used in this study, having the least viable counts at all 3 storage temperatures. Probiotics stored in rice maltodextrin, on average, had higher probiotic counts compared to those stored in potato maltodextrin. Study suggests that to provide consumers with 108 to 1010 CFU/d of probiotic cells, robust bacterial strains, suitable carriers, and a storage temperature of 4 degrees C are required. PMID- 27681166 TI - Cervical intraepithelial neoplasia (CIN) 3-like squamous cell carcinoma of the cervix: a review of 14 cases with comparison of E-cadherin and cyclin D1 expression in the CIN 3-like and infiltrative tumour elements. AB - AIMS: To review the clinicopathological features of 14 cases of CIN 3-like squamous cell carcinoma (SCC) of the cervix and to investigate possible mechanisms of tumour invasion in the CIN 3-like and 'conventional' (infiltrative) tumour components. METHODS AND RESULTS: The median patient age was 43.4 years. Of the 12 cases with known stage, eight were stage IB and four were stage II. Initial biopsies were often misinterpreted as CIN 3 alone or CIN 3 with only superficial stromal invasion, and eight patients underwent multiple biopsy procedures prior to definitive diagnosis: upon review, an earlier diagnosis was possible in six of these cases. Nine tumours exhibited both CIN 3-like and conventional tumour components. The former usually demonstrated an E-cadherin positive and cyclin D1-negative immunophenotype, whereas conventional SCC more often showed loss of E-cadherin and cyclin D1 staining at the margin of larger tumour nests and in smaller invasive clusters. CONCLUSION: Cervical SCCs demonstrating a CIN 3-like growth pattern continue to present diagnostic difficulty and are often misinterpreted as non-invasive/minimally invasive disease. The morphology and immunophenotype suggest a process of collective cellular invasion in CIN 3-like SCC, whereas corresponding conventional SCC elements show features consistent with epithelial-mesenchymal transition. PMID- 27681167 TI - Time- and frequency-domain analysis of beat to beat P-wave duration, PR interval and RR interval can predict asystole as form of syncope during head-up tilt. AB - To seek possible differences in short-period temporal RR interval, P-wave and PR interval dispersion and spectral coherence in patients with a head-up tilt test positive for vasovagal syncope with or without prolonged asystole, severe symptoms and at high risk of trauma. We retrospectively reviewed 5 min ECG and blood pressure recordings obtained at baseline, at rest and during head-up tilt in 40 patients diagnosed as having recurrent vasovagal syncope confirmed at a head-up tilt test. We analysed autoregressive spectral power for all the ECG derived variables, focusing on temporal P-wave and PR interval dispersion indexes as well as their spectral coherence calculated on the same 5 min recordings at rest and during tilt. ECG recordings obtained during tilt before syncope showed significantly lower P -> PR spectral coherence and higher RR standard deviations in patients with tilt-induced asystole than in those without (0.567 +/- 0.097 versus 0.670 +/- 0.127, p: 0.010 and 84 +/- 36 versus 46 +/- 22 ms2, p < 0.0001). Differences in the RR standard deviations persisted also on the last hundred beats (-100) (113 +/- 54 versus 34 +/- 17 ms2, p < 0.0001). Multiple regression analysis identified a significantly negative association between the maximum RR intervals and P -> PR coherence at rest (beta: -0.3, p < 0.05) and positive association with RR-100 standard deviation during tilt-induced syncope (beta: 0.621, p < 0.001). P -> PR spectral coherence could be used to assess the risk of prolonged asystole in patients with tilt-induced vasovagal syncope as well as as a possible surrogate for tilt testing during these patients' follow-up. PMID- 27681168 TI - Irving I. Gottesman (1930-2016): the multifactorial threshold model of complex phenotypes mediated by endophenotype strategies. PMID- 27681169 TI - Another Step Closer to Understanding Plant Cell Wall Biosynthesis: The Crystal Structure of FUCOSYLTRANSFERASE1. PMID- 27681171 TI - Complications and Failure of Endovenous Laser Ablation and Radiofrequency Ablation Procedures in Patients With Lower Extremity Varicose Veins in a 5-Year Follow-Up. AB - INTRODUCTION: Thermal ablation techniques have gradually replaced Babcock procedure in varicose vein treatment. AIM: A comparative quantitative-qualitative analysis of complications and failure of endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in a 5-year follow-up. MATERIALS AND METHODS: One hundred ten adult participants with varicose veins clinical grade C2 to C6, treated for isolated great saphenous vein (GSV) or small saphenous vein (SSV) insufficiency in a single lower extremity in 2009 to 2010, were enrolled and subdivided into EVLA (n = 56) and RFA (n = 54) groups. Both groups were compared for demography, disease stage, affected veins, perioperative, and postoperative complications as well as treatment efficacy. RESULTS: The perioperative and postoperative complications were statistically insignificant. Treatment efficacy, expressed as the number of participants with recurrent varicosity and recanalization, was comparable in both groups. The clinically significant recanalization rate was 3.6% and 5.6% in EVLA and RFA groups, respectively. CONCLUSION: Endovenous laser ablation and RFA for the management of lower extremity varicose vein offer comparable efficacy and safety in a 5-year follow up. PMID- 27681170 TI - Transcriptional Activation of Two Delta-9 Palmitoyl-ACP Desaturase Genes by MYB115 and MYB118 Is Critical for Biosynthesis of Omega-7 Monounsaturated Fatty Acids in the Endosperm of Arabidopsis Seeds. AB - In angiosperms, double fertilization of the embryo sac initiates the development of the embryo and the endosperm. In Arabidopsis thaliana, an exalbuminous species, the endosperm is reduced to one cell layer during seed maturation and reserves such as oil are massively deposited in the enlarging embryo. Here, we consider the strikingly different fatty acid (FA) compositions of the oils stored in the two zygotic tissues. Endosperm oil is enriched in omega-7 monounsaturated FAs, that represent more than 20 mol% of total FAs, whereas these molecular species are 10-fold less abundant in the embryo. Two closely related transcription factors, MYB118 and MYB115, are transcriptionally induced at the onset of the maturation phase in the endosperm and share a set of transcriptional targets. Interestingly, the endosperm oil of myb115 myb118 double mutants lacks omega-7 FAs. The identification of two Delta9 palmitoyl-ACP desaturases responsible for omega-7 FA biosynthesis, which are activated by MYB115 and MYB118 in the endosperm, allows us to propose a model for the transcriptional control of oil FA composition in this tissue. In addition, an initial characterization of the structure-function relationship for these desaturases reveals that their particular substrate specificity is conferred by amino acid residues lining their substrate pocket that distinguish them from the archetype Delta9 stearoyl-ACP desaturase. PMID- 27681172 TI - Surgical Revascularization of Symptomatic Kinking of the Internal Carotid Artery. AB - OBJECTIVE: To evaluate the safety and outcomes of surgical revascularization for patients with symptomatic kinking of the internal carotid artery (ICA). METHODS: Twenty-five consecutive patients presented with symptomatic kinking of the ICA and a history of transient ischemic attack (TIA) or stroke were prospectively enrolled in this study. All patients were treated with ICA transection and end-to side reimplantation at the level of the carotid bulb. Patients were followed up for a median of 32 months. RESULTS: There were no deaths or strokes within the 30 days of the treatment. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. One (4%) patient had temporary recurrent nerve palsy, which was completely recovered at 4-week follow-up. One (4%) patient had a myocardial ischemic event. At the end of the 32-month follow-up, 1 (4%) patient developed ipsilateral minor stroke. No recurrent stenosis was detected by Doppler ultrasound. CONCLUSION: Surgical treatment for isolated, symptomatic kinking of the ICA and a history of TIA or stroke is safe, and the outcomes are acceptable. PMID- 27681173 TI - Inhibitory Effect of TLR4 Gene Silencing on Intimal Hyperplasia of Vein Grafting. AB - PURPOSE: The present study aimed to explore the regulating effect of Toll-like receptor 4 (TLR4) on intimal hyperplasia in rat vein grafts. METHODS: Rat models of external jugular vein carotid artery bypass grafting were established. Afterward, TLR4 small interfering RNA (siRNA) recombinant plasmids were constructed, which were transfected into rat vein graft bypass to study the effect of TLR4 silencing on intimal hyperplasia and to explore the underlying mechanisms. Real-time polymerase chain reaction and Western blot were used to detect the expression levels of TLR4 and inflammatory factors in TLR4 siRNA transfected vein graft bypass. The intimal thickness was evaluated using hematoxylin-eosin staining. RESULTS: Compared with the scramble siRNA group, the intimal thickness of vein grafting was decreased significantly, while the inflammatory factors including interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha in grafted vein were dramatically downregulated in the TLR4 siRNA group. CONCLUSION: These results showed that local silencing of TLR4 in the vein grafts could inhibit intimal hyperplasia by downregulating the expression of inflammatory factors in the vein grafts, suggesting that TLR4 can be used as a new target for therapy of vascular intimal hyperplasia. PMID- 27681174 TI - Too much to differentiate: aneuploidy promotes proliferation and teratoma formation in embryonic stem cells. PMID- 27681176 TI - Hematopoietic stem and progenitor cells as novel prognostic biomarkers of longevity in a murine model for amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a difficult diagnosis and prognosis. In this regard, new and more reliable biomarkers for the disease are needed. We propose peripheral blood, and, more specifically, the hematopoietic stem and progenitor cells (HSPCs) as potential prognostic biomarkers in the SOD1G93A murine model of ALS. We accurately and serially studied three HSPCs-hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs)-in both control and SOD1G93A mice along the disease's progression by RT-PCR and flow cytometry analysis. We found interesting differences for every HSPC type in the transgenic mice compared with the control mice at every time point selected, as well as differences along the disease course. The results showed a maintained compensatory increase of HSCs along disease progression. However, the downregulated levels of CLPs and CMPs suggested an exit of these cell populations to the peripheral tissues, probably due to their supporting role to the damaged tissues. In addition, a positive correlation of the percentage of CLPs and CMPs with the longevity was found, as well as a positive correlation of HSCs and CMPs with motor function and weight, thus reinforcing the idea that HSPCs play a relevant role in the longevity of the SOD1G93A mice. On the basis of these results, both CLPs and CMPs could be considered prognostic biomarkers of longevity in this animal model, opening the door to future studies in human patients for their potential clinical use. PMID- 27681175 TI - Towards a DNA Barcode Reference Database for Spiders and Harvestmen of Germany. AB - As part of the German Barcode of Life campaign, over 3500 arachnid specimens have been collected and analyzed: ca. 3300 Araneae and 200 Opiliones, belonging to almost 600 species (median: 4 individuals/species). This covers about 60% of the spider fauna and more than 70% of the harvestmen fauna recorded for Germany. The overwhelming majority of species could be readily identified through DNA barcoding: median distances between closest species lay around 9% in spiders and 13% in harvestmen, while in 95% of the cases, intraspecific distances were below 2.5% and 8% respectively, with intraspecific medians at 0.3% and 0.2%. However, almost 20 spider species, most notably in the family Lycosidae, could not be separated through DNA barcoding (although many of them present discrete morphological differences). Conspicuously high interspecific distances were found in even more cases, hinting at cryptic species in some instances. A new program is presented: DiStats calculates the statistics needed to meet DNA barcode release criteria. Furthermore, new generic COI primers useful for a wide range of taxa (also other than arachnids) are introduced. PMID- 27681177 TI - N-glycosylation critically regulates function of oxalate transporter SLC26A6. AB - The brush border Cl--oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. Through a series of enzymatic deglycosylation studies we confirmed that endogenously expressed mouse and human SLC26A6 are indeed glycosylated, that the oligosaccharides are principally attached via N glycosidic linkage, and that there are tissue-specific differences in glycosylation. In vitro cell culture experiments were then used to elucidate the functional significance of the addition of the carbohydrate moieties. Biotinylation studies of SLC26A6 glycosylation mutants indicated that glycosylation is not essential for cell surface delivery of SLC26A6 but suggested that it may affect the efficacy with which it is trafficked and maintained in the plasma membrane. Functional studies of transfected SLC26A6 demonstrated that glycosylation at two sites in the putative second extracellular loop of SLC26A6 is critically important for chloride-dependent oxalate transport and that enzymatic deglycosylation of SLC26A6 expressed on the plasma membrane of intact cells strongly reduced oxalate transport activity. Taken together, these studies indicated that oxalate transport function of SLC26A6 is critically dependent on glycosylation and that exoglycosidase-mediated deglycosylation of SLC26A6 has the capacity to profoundly modulate SLC26A6 function. PMID- 27681180 TI - Mechanotransduction of the endothelial glycocalyx mediates nitric oxide production through activation of TRP channels. AB - The endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer found on the vascular endothelium, serving critical functions in the mechanotransduction of blood flow-induced forces. One of the most important protective functions of the ESG is to mediate the production of nitric oxide (NO) in response to blood flow. However, the detailed mechanism underlying ESG's mechanotransduction of the production of NO has not been completely identified. Herein, using the cultured rat brain microvascular endothelial cells (bEnd.3) as a model system, we have implemented a combined atomic force and fluorescence microscopy approach to show that the ESG senses and transduces vertical mechanical stretch to produce NO. This rapid NO production is dependent on the presence of both heparan sulfate (HS) and hyaluronic acid (HA) in ESG, as the removal of HS and/or HA leads to a significant decrease in NO production. Moreover, the production of NO is dependent on the intake of Ca2+ via endothelial transient receptor potential (TRP) channels. Together, our results demonstrate the molecular mechanism of rapid production of NO in response to vertical mechanical stretch. PMID- 27681178 TI - Expression of the mitochondrial calcium uniporter in cardiac myocytes improves impaired mitochondrial calcium handling and metabolism in simulated hyperglycemia. AB - Diabetic cardiomyopathy is associated with metabolic changes, including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial Ca2+ uniporter (MCU) is the channel responsible for Ca2+ uptake in mitochondria, and free mitochondrial Ca2+ concentration ([Ca2+]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed reduced [Ca2+]m and MCU protein levels. Therefore, we investigated whether returning [Ca2+]m to normal levels in CM by MCU expression could lead to normalization of Gox and FAox with no detrimental effects. Mouse neonatal CM were exposed for 72 h to normal glucose [5.5 mM glucose + 19.5 mM mannitol (NG)], high glucose [25 mM glucose (HG)], or HG + adenoviral MCU expression. Gox and FAox, [Ca2+]m, MCU levels, pyruvate dehydrogenase (PDH) activity, oxidative stress, mitochondrial membrane potential, and apoptosis were assessed. [Ca2+]m and MCU protein levels were reduced after 72 h of HG. Gox was decreased and FAox was increased in HG, PDH activity was decreased, phosphorylated PDH levels were increased, and mitochondrial membrane potential was reduced. MCU expression returned these parameters toward NG levels. Moreover, increased oxidative stress and apoptosis were reduced in HG by MCU expression. We also observed reduced MCU protein levels and [Ca2+]m in hearts from type 1 diabetic mice. Thus we conclude that HG-induced metabolic alterations can be reversed by restoration of MCU levels, resulting in return of [Ca2+]m to normal levels. PMID- 27681179 TI - Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH. AB - The SLC4A11 gene encodes the bicarbonate-transporter-related protein BTR1, which is mutated in syndromes characterized by vision and hearing loss. Signs of these diseases [congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome] are evident in mouse models of Slc4a11 disruption. However, the intrinsic activity of Slc4a11 remains controversial, complicating assignment of its (patho)physiological role. Most studies concur that Slc4a11 transports H+ (or the thermodynamically equivalent species OH-) rather than HCO3-, but disparities have arisen as to whether the transport is coupled to another species such as Na+ or NH3/NH4+ Here for the first time, we examine the action of mouse Slc4a11 in Xenopus oocytes. We simultaneously monitor changes in intracellular pH, membrane potential, and conductance as we alter extracellular pH, revealing the electrical and chemical driving forces that underlie the observed ion fluxes. We find that mSlc4a11 is an ideally selective H+/OH- conductive pathway, the action of which is uncoupled from the cotransport of any other ion. We also find that the activity of mSlc4a11 is independently enhanced by both extracellular and intracellular alkalinization, suggesting OH- as the most likely substrate and providing a novel explanation for the apparent NH3-dependence of Slc4a11-mediated currents reported by others. We suggest that the unique properties of Slc4a11 action underlie its value as a pH regulator in corneal endothelial cells. PMID- 27681183 TI - Stroke outcomes: A consumer perspective. AB - The context of each stroke is at once universal and uniquely personal. From the perspective of the consumer, stroke rehabilitation is just one moment in the lifework of recovery, compensation, and adaptation. Using a single case example, the experience of one stroke survivor and family illustrates the context of stroke recovery and the potential impacts of family members and caregivers on optimal stroke outcomes. The insights and implications for professionals focus on individualizing rehabilitation, developing the capacity of families and caregivers to maximize functional gains, and empowering consumers to be daring in reclaiming roles and activities threatened by disability. PMID- 27681181 TI - Unsupervised learning in probabilistic neural networks with multi-state metal oxide memristive synapses. AB - In an increasingly data-rich world the need for developing computing systems that cannot only process, but ideally also interpret big data is becoming continuously more pressing. Brain-inspired concepts have shown great promise towards addressing this need. Here we demonstrate unsupervised learning in a probabilistic neural network that utilizes metal-oxide memristive devices as multi-state synapses. Our approach can be exploited for processing unlabelled data and can adapt to time-varying clusters that underlie incoming data by supporting the capability of reversible unsupervised learning. The potential of this work is showcased through the demonstration of successful learning in the presence of corrupted input data and probabilistic neurons, thus paving the way towards robust big-data processors. PMID- 27681184 TI - How to engage families in stroke rehabilitation. AB - The involvement and support of the family are vital in stroke rehabilitation. Stroke can have a devastating effect on family relationships. The primary goal of rehabilitation is to help the stroke survivor and family maximize their resources and capabilities to address the reality of stroke survivorship. This is achieved through the combined efforts of the stroke survivor, the family, and the treatment team. PMID- 27681182 TI - Evolutionary History and Ongoing Transmission of Phylogenetic Sublineages of Mycobacterium tuberculosis Beijing Genotype in China. AB - Mycobacterium tuberculosis Beijing genotype originated in China and has undergone a dramatic population growth and global spread in the last century. Here, a collection of M. tuberculosis Beijing family isolates from different provinces across all China was genotyped by high-resolution (24-MIRU-VNTR) and low resolution, high-rank (modern and ancient sublineages) markers. The molecular profiles and global and local phylogenies were compared to the strain phenotype and patient data. The phylogeographic patterns observed in the studied collection demonstrate that large-scale (but not middle/small-scale) distance remains one of the decisive factors of the genetic divergence of M. tuberculosis populations. Analysis of diversity and network topology of the local collections appears to corroborate a recent intriguing hypothesis about Beijing genotype originating in South China. Placing our results within the Eurasian context suggested that important Russian B0/W148 and Asian/Russian A0/94-32 epidemic clones of the Beijing genotype could trace their origins to the northeastern and northwestern regions of China, respectively. The higher clustering of the modern isolates in children and lack of increased MDR rate in any sublineage suggest that not association with drug resistance but other (e.g., speculatively, virulence related) properties underlie an enhanced dissemination of the evolutionarily recent, modern sublineage of the Beijing genotype in China. PMID- 27681186 TI - Neurocognitive rehabilitation guidelines for therapists. AB - Establishing and implementing cognitive rehabilitation (CR) plans requ i re the efforts of al I rehabilitation staff members. In addition to clear expectations about therapists' roles and responsibilities, there are other issues that need to be considered when creating CR protocols. Specifically, the patient's insight into his or her deficits is a crucial consideration when establishing a CR plan. Other factors also need to be examined, such as the role of the family, the method of establishing goals and monitoring progress, and the necessity of providing feedback to the patient. This article addresses these issues and provides guidelines for rehabilitation teams to establish CR plans. PMID- 27681185 TI - Families and stroke: The clinical implications of research findings. AB - Clinical and research attention to stroke care has focused on managing the acute stage of recovery and on evaluating the short-term effectiveness of rehabilitation programs. However, studies suggest that stroke affects the quality of life and the well-being of the entire family over much longer time frames. This article reviews the stroke literature as it relates to stroke rehabilitation and the family. Research findings strongly suggest that stroke is a family affair and that more rigorous attention to family assessment, education, advocacy, and counseling is needed along with development of new intervention methods focused on addressing specific family dimensions that have a demonstrated relationship to specific stroke problems. It is clear that health professionals shou Id thi nk farm ly, involvethefamily, and work with the family. PMID- 27681188 TI - Psychobehavioral problems other than depression in stroke. AB - With the exception of depression and cognitive changes, there has been relatively little attention paid to psychiatric disorders or to psychosocial and behavioral changes that may present after stroke. This article addresses that deficiency by reviewing psychiatric symptoms and syndromes and other psychosocial and behavioral problems that may present in the stroke survivor: mood disorders other than unipolar depression, anxiety and adjustment disorders, substance abuse, sexual dysfunction, sleep disturbance, organic mental disorders, and behavioral problems. The special concerns and functional impact these presentations have in the stroke population are discussed along with diagnostic and treatment options. PMID- 27681187 TI - Depression and stroke. AB - Depression in stroke patients was observed many years ago but only recently has become the subject of systematic study. While estimates of depression vary, some have noted its occurrence in more than half of stroke patients. Our understanding of depression has been facilitated by refinements in diagnostic categories, analysis of contributing factors including the biology of depression, and refinements in evaluation to include cognitive and linguistic impairments that are common after stroke. The ways in which depression may affect rehabilitation and the fate of depression over time have been the subject of recent studies. Management includes sensitizing of caregivers, environmental change, education for patients and families, psychotherapy, and pharmacological interventions. PMID- 27681189 TI - Psychopharmacology and stroke. AB - The use of psychopharmacology for stroke patients requires careful attention to diagnosis, selection of medications for a particular use and avoidance of specific actions that interfere with recovery and function, and careful monitoring for results and side effects. Any given psychotropic medication may be used to treat a number of psychiatric and other problems. This review focuses on specific clinical implications for the use of antipsychotic, antidepressant, psychostimulant, antimanic, anxiolytic, and other selected agents in stroke. PMID- 27681191 TI - New technologies and intrvention approaches: A new look at aphasia groups. PMID- 27681190 TI - Ethical issues arising in the care of stroke patients in the era of managed care. PMID- 27681192 TI - From the editor. PMID- 27681194 TI - Letters To The Editors. PMID- 27681193 TI - Foreword. PMID- 27681196 TI - pH and Organic Carbon Dose Rates Control Microbially Driven Bioremediation Efficacy in Alkaline Bauxite Residue. AB - Bioremediation of alkaline tailings, based on fermentative microbial metabolisms, is a novel strategy for achieving rapid pH neutralization and thus improving environmental outcomes associated with mining and refining activities. Laboratory scale bioreactors containing bauxite residue (an alkaline, saline tailings material generated as a byproduct of alumina refining), to which a diverse microbial inoculum was added, were used in this study to identify key factors (pH, salinity, organic carbon supply) controlling the rates and extent of microbially driven pH neutralization (bioremediation) in alkaline tailings. Initial tailings pH and organic carbon dose rates both significantly affected bioremediation extent and efficiency with lower minimum pHs and higher extents of pH neutralization occurring under low initial pH or high organic carbon conditions. Rates of pH neutralization (up to 0.13 mM H+ produced per day with pH decreasing from 9.5 to <=6.5 in three days) were significantly higher in low initial pH treatments. Representatives of the Bacillaceae and Enterobacteriaceae, which contain many known facultative anaerobes and fermenters, were identified as key contributors to 2,3-butanediol and/or mixed acid fermentation as the major mechanism(s) of pH neutralization. Initial pH and salinity significantly influenced microbial community successional trajectories, and microbial community structure was significantly related to markers of fermentation activity. This study provides the first experimental demonstration of bioremediation in bauxite residue, identifying pH and organic carbon dose rates as key controls on bioremediation efficacy, and will enable future development of bioreactor technologies at full field scale. PMID- 27681198 TI - Fine-Tuning of the Coordination Environment To Regulate the Magnetic Behavior in Solvent/Anion-Dependent DyIII Compounds: Synthesis, Structure, Magnetism, and Ab Initio Calculations. AB - It is crucial to understand and elucidate the self-assembly mechanism in solution systems for the construction of DyIII-based single-molecule magnets (SMMs). Herein, through fine-tuning of the anion and solvent, we prepared three nine coordinate mononuclear dysprosium compounds, [Dy(2,3'-pcad)(NO3)2(CH3OH)2] (1), [Dy(2,3'-Hpcad)2(H2O)3].3Cl.5H2O (2), and [Dy(2,3'-pcad)(NO3)(H2O)4].NO3.H2O (3) [2,3'-Hpcad = N3-(2-pyridoyl)-3-pyridinecarboxamidrazone]. The reactions of formation for 1-3 are in situ thermodynamically monitored by isothermal titration calorimetry. Magnetic data analysis reveals that 2 shows SMM behavior under a zero direct-current (dc) field, whereas 1 and 3 exhibit distinct slow magnetic relaxation processes upon a 1200 Oe dc field. To deeply understand the different magnetic behaviors, the magnetic anisotropy of 1-3 has been systematically studied by ab initio calculations, which is consistent with the experimental observations. Moreover, the semiconductor behaviors of 1-3 have been investigated by experimental measurements of UV-vis spectroscopy. PMID- 27681199 TI - Effects of Nanoporous Carbon Derived from Microalgae and Its CoO Composite on Capacitance. AB - Nanoporous carbon was synthesized from microalgae as a promising electrode material for electric double layer capacitors due to its large specific surface area and controllable pore structures. The pore textural properties of the algae derived-carbon (ADC) samples were measured by N2 adsorption and desorption at 77 K. The performance of the activated carbon (AC) as supercapacitor electrodes was determined by the cyclic voltammetry and galvanostatic charge/discharge tests. The effect of the nanoporous carbon structure on capacitance was demonstrated by calculating the contributions of micropores and mesopores toward capacitance. Capacitance was significantly affected by both pore size and pore depth. To further increase the specific capacity, a single-pot synthesis of porous carbon supported CoO composite (CoO/ADC) electrode material was developed using microalgae as the carbon source and Co(OH)2 as both a carbon activation agent and CoO precursor. After carbonization, CoO particles were formed and embedded in the ADC matrix. The synergic contributions from the combined CoO and ADC resulted in better supercapacitor performance as compared to that of the pure CoO electrode. The calculated specific capacities of CoO/ADC were 387 and 189 C g-1 at 0.2 and 5 A g-1, respectively, which were far more than the capacities of pure CoO electrode (185 C g-1 at 0.2 A g-1 and 77 C g-1 at 5 A g-1). The cycle stability of CoO/ADC also increased significantly (83% retention of the initial capacity for CoO/ADC vs 63% for pure CoO). This research had developed a viable and promising solution for producing composite electrodes in a large quantity for commercial application. PMID- 27681200 TI - Ultrafast Raman Spectroscopy as a Probe of Local Structure and Dynamics in Photoexcited Conjugated Materials. AB - An important challenge in the study of conjugated organic materials is to relate the properties of transient states underlying macroscopic material responses directly with intra- and intermolecular structure. We discuss recent efforts using the vibrational sensitivity of time-resolved Raman spectroscopy to interrogate structural properties of transient excited and charge-separated states in conjugated oligomers and polymers in order to relate them to molecular conformations and material microstructures. We focus on recent work with excited state Raman spectroscopy that provides mode-specific signatures of structural relaxation in oligo- and polythiophenes, examination of structural heterogeneities associated with exciton localization in different structural motifs of amorphous polymers, and interrogation of correlations between microstructure and properties and dynamics of charge-separated states within polymer aggregates. On the basis of these recent efforts, we provide an outlook for further applying this method to elucidate relationships between the structure and properties of transient states and the photoresponses of conjugated materials. PMID- 27681197 TI - Mycobacterium tuberculosis multi-drug-resistant strain M induces IL-17+ IFNgamma- CD4+ T cell expansion through an IL-23 and TGF-beta-dependent mechanism in patients with MDR-TB tuberculosis. AB - We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD+ HD)] by the M strain and the laboratory strain H37Rv. Our results show that IL-1beta and IL-6 are crucial for the H37Rv and M induced expansion of IL-17+ interferon (IFN)-gamma- and IL-17+ IFN-gamma+ in CD4+ T cells from MDR-TB and PPD+ HD. IL-23 plays an ambiguous role in T helper type 1 (Th1) and Th17 profiles: alone, IL-23 is responsible for M. tuberculosis-induced IL-17 and IFN-gamma expression in CD4+ T cells from PPD+ HD whereas, together with transforming growth factor (TGF-beta), it promotes IL-17+ IFN-gamma- expansion in MDR-TB. In fact, spontaneous and M. tuberculosis-induced TGF-beta secretion is increased in cells from MDR-TB, the M strain being the highest inducer. Interestingly, Toll-like receptor (TLR)-2 signalling mediates the expansion of IL-17+ IFN-gamma- cells and the enhancement of latency-associated protein (LAP) expression in CD14+ and CD4+ T cells from MDR-TB, which suggests that the M strain promotes IL-17+ IFN-gamma- T cells through a strong TLR-2 dependent TGF-beta production by antigen-presenting cells and CD4+ T cells. Finally, CD4+ T cells from MDR-TB patients infected with MDR Haarlem strains show higher IL-17+ IFN-gamma- and lower IL-17+ IFN-gamma+ levels than LAM-infected patients. The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response. PMID- 27681201 TI - Palladium/Lewis Acid Co-catalyzed Divergent Asymmetric Ring-Opening Reactions of Azabenzonorbornadienes with Alcohols. AB - By fine tuning the combinations of chiral palladium catalysts and Lewis acids, both the additional and reductive asymmetric ring-opening reactions of azabenzonorbornadienes with alcohols were accomplished with good chemoselectivity, regioselectivity, and enantioselectivity. It was proven that the reductive ring-opening products were generated through a transfer hydrogenation process with alcohols as hydrogen source. PMID- 27681202 TI - Increasing Prevalence Rate of Nontuberculous Mycobacteria Infections in Five States, 2008-2013. AB - RATIONALE: Many nontuberculous mycobacteria (NTM) are clinically significant pathogens that cause disease in a variety of different human organs and tissues. OBJECTIVES: A population-based study was undertaken to investigate the prevalence of patients with a positive specimen for NTM within five states of the United States. METHODS: We determined the case and age distribution of patients with at least one specimen positive for NTM, using data submitted to the disease surveillance systems of five states (Maryland, Mississippi, Missouri, Ohio, and Wisconsin) between 2008 and 2013. Crude, age-specific, and age-adjusted prevalence rates per 100,000 persons were calculated for each state. MEASUREMENTS AND MAIN RESULTS: From 2008 to 2013, a total of 24,226 NTM cases were reported to the disease surveillance systems of the five states. The overall average annual age-adjusted prevalence rate rose from 8.7 to 13.9 per 100,000 persons between the beginning and end of the surveillance period. The number of cases and case rate in the 50-80+-year age group was higher than in the 0-49-year age group. Prevalence by age category differed among the five states. The highest number of NTM cases was observed in Mississippi for the 80+-year age group, whereas Wisconsin observed the highest number of NTM cases in the 60- to 69-year age group. CONCLUSIONS: From 2008 to 2013, the number of patients with positive specimens for NTM rose. This trend is likely to continue in the coming decade as the U.S. population ages. To reduce the prevalence of NTM infections, medical guidance for susceptible populations is needed regarding actions that can be taken to avoid sources and routes of exposure to NTMs if the disease burden is to be reduced. PMID- 27681203 TI - Large low field magnetocaloric effect in first-order phase transition compound TlFe3Te3 with low-level hysteresis. AB - Magnetic refrigeration based on the magnetocaloric effect (MCE) is an environment friendly, high-efficiency technology. It has been believed that a large MCE can be realized in the materials with a first-order magnetic transition (FOMT). Here, we found that TlFe3Te3 is a ferromagnetic metal with a first-order magnetic transition occurring at Curie temperature TC = 220 K. The maximum values of magnetic entropy change (Delta) along the crystallographic c-axis, estimated from the magnetization data, reach to 5.9 J kg-1K-1 and 7.0 J kg-1 K-1 for the magnetic field changes, DeltaH = 0-1 T and 0-2 T, respectively, which is significantly larger than that of MCE materials with a second-order magnetic transition (SOMT). Besides the large DeltaSM, the low-level both thermal and field hysteresis make TlFe3Te3 compound an attractive candidate for magnetic refrigeration. Our findings should inspire the exploration of high performance new MCE materials. PMID- 27681204 TI - Deconstructing negative pressure wound therapy. AB - Since its introduction 20 years ago for the treatment of chronic wounds, negative pressure wound therapy use has expanded to a variety of other wound types. Various mechanisms of action for its efficacy in wound healing have been postulated, but no unifying theory exists. Proposed mechanisms include induction of perfusion changes, microdeformation, macrodeformation, exudate control and decreasing the bacterial load in the wound. We surmise that these different mechanisms have varying levels of dominance in each wound type. Specifically, negative pressure wound therapy is beneficial to acute open wounds because it induces perfusion changes and formation of granulation tissue. Post-surgical incisional wounds are positively affected by perfusion changes and exudate control. In the context of chronic wounds, negative pressure wound therapy removes harmful and corrosive substances within the wounds to affect healing. When skin grafts and dermal substitutes are used to close a wound, negative pressure wound therapy is effective in promoting granulation tissue formation, controlling exudate and decreasing the bacterial load in the wound. In this review, we elucidate some of the mechanisms behind the positive wound healing effects of negative pressure wound therapy, providing possible explanations for these effects in different wound types. PMID- 27681205 TI - Taking actions to quit chewing betel nuts and starting a new life: taxi drivers' successful experiences of quitting betel nut chewing. AB - AIMS AND OBJECTIVES: To understand taxi drivers' successful experiences of quitting betel nut chewing. BACKGROUND: Previous studies verified that betel nut chewing significantly increases the risk of oral cancer. In Taiwan, taxi drivers work for approximately 10-13 hours per day, and 31.7-80% of them choose to chew betel nuts for their invigorating qualities, which enable them to work more hours and receive more income. DESIGN: A qualitative research design was used. METHODS: This study used the grounded theory method with purposive sampling to perform in depth interviews with male taxi drivers who had successfully quit betel nut chewing for more than six months. RESULTS: The interviewed participants were 25 taxi drivers aged 45-67 who had chewed betel nuts for an average of 30.9 years. A constant comparative analysis of the 25 interviews revealed six categories, namely the first experience of chewing betel nuts, a part of work and life, perceiving the impact of betel nuts, trying to change, acting to quit betel nut chewing and starting a new life. CONCLUSIONS: During the cessation process, taxi drivers tended to be affected by their addiction to chewing betel nuts and the temptation of friends' invitations to chew betel nuts. However, their recognition of the physical effects of betel nut chewing and their sense of responsibility and commitment to family were the critical factors affecting their determination to quit betel nut chewing. Their willpower to not to chew betel nuts and the source of their motivation to exercise self-control also contributed to their success. RELEVANCE TO CLINICAL PRACTICE: Healthcare personnel should understand the experiences and perceptions of betel nut chewers, strengthen their understanding of the effects of betel nut chewing on physical health during the cessation period and support their self-efficacy and quitting behaviours with the assistance of significant others. PMID- 27681206 TI - Who attends a Children's Hospital Emergency Department for dental reasons? A two step cluster analysis approach. AB - OBJECTIVES: Emergency departments (EDs) have been identified as key providers of dental care although few studies have examined patterns of attendance or clusters of characteristics. The aim was to identify the reasons for visits to an ED, whether these remained stable over time, and characterize clusters of patients by socio-demographic and attendance variables. METHODS: Pseudonymized data were obtained for children who attended the ED in 2003-2004, 2004-2005 and 2012-2013. Presenting complaint was categorized as attending for dental or nondental reasons. Other variables analysed included patient (age, sex, ethnicity and deprivation) and attendance characteristics (distance travelled, season, nature of complaint, time elapsed since onset of symptoms, day of week and hours of attendance), together with treatment outcome (advice, antibiotics and referral). To assess trends over time, analyses were conducted on patient, attendance and treatment outcome variables. To examine whether patients could be characterized by socio-demographic and attendance variables, a two-step cluster analysis was undertaken on 2003-2004 data set and validated on 2004-2005 and 2012-2013 data sets. RESULTS: In 2003-2004, 550 children attended the ED for dental reasons rising to 687 in 2012-2013. The most important predictors of dental attendance were as follows: nature of complaint, ethnicity, time elapsed, sex and deprivation of the area in which children lived. The analysis showed two clusters: cluster 1 was comprised of children who attended the ED for dental injury, were of White ethnicity and attended within 24 h of onset of symptoms. Children in this cluster were likely to be from the least or less deprived areas (compared to Cluster 2) and were more likely to be males. Cluster 2 comprised of children attending the ED for caries, oral mucosal lesions or other complaints, were likely to be of other (non-White) ethnicities and were likely to attend more than 24 h after symptoms began. Children in this cluster were more likely to come from the most deprived areas and were both males and females. The clusters varied according to treatment outcome; those patients in Cluster 2 were more likely to be prescribed medication, whilst those children in Cluster 1 were more likely to be referred to another specialty. CONCLUSIONS: A significant number of visits to the ED were for dental reasons with two clusters of children. The results have identified groups of patients for whom appropriate dental provision is lacking and where targeted services are needed to improve outcomes for children and reduce the burden on EDs. PMID- 27681207 TI - Multi-iPPseEvo: A Multi-label Classifier for Identifying Human Phosphorylated Proteins by Incorporating Evolutionary Information into Chou's General PseAAC via Grey System Theory. AB - Predicting phosphorylation protein is a challenging problem, particularly when query proteins have multi-label features meaning that they may be phosphorylated at two or more different type amino acids. In fact, human protein usually be phosphorylated at serine, threonine and tyrosine. By introducing the "multi-label learning" approach, a novel predictor has been developed that can be used to deal with the systems containing both single- and multi-label phosphorylation protein. Here we proposed a predictor called Multi-iPPseEvo by (1) incorporating the protein sequence evolutionary information into the general pseudo amino acid composition (PseAAC) via the grey system theory, (2) balancing out the skewed training datasets by the asymmetric bootstrap approach, and (3) constructing an ensemble predictor by fusing an array of individual random forest classifiers thru a voting system. Rigorous cross-validations via a set of multi-label metrics indicate that the multi-label phosphorylation predictor is very promising and encouraging. The current approach represents a new strategy to deal with the multi-label biological problems, and the software is freely available for academic use at http://www.jci-bioinfo.cn/Multi-iPPseEvo. PMID- 27681208 TI - The effectiveness of habit reversal on treatment outcome and quality of life in patients with chronic eczema: a prospective observational study in the U.K. PMID- 27681209 TI - Effects of dam parity and pre-weaning average daily gain of Holstein calves on future milk production. AB - This research communication describes relationships between pre-weaning average daily gain (ADG) and dam parity with future productivity of dairy calves. Higher ADG before weaning has been shown to be related to greater milk production in the first lactation of Holstein calves fed milk replacer. However, data is limited on the relationship between pre-weaning ADG and first lactation performance of Holstein calves fed whole milk. Data of three hundred and thirty-two Holstein calves from 35 primiparous and 297 multiparous cows was investigated to evaluate the relationship between the dam parity and pre-weaning ADG with the first lactation performance. Results indicated that birth (P < 0.01), and weaning body weight (P < 0.001) were greater in calves born from multiparous cows. Neither 305 d milk production nor pre-weaning ADG differed significantly between calves born to primiparous or multiparous cows, although milk yield tended to be higher in the former and ADG higher in the latter. Correlations between 305 d milk yield and pre-weaning ADG, dam parity and birth body weight were low and non significant, although there was a tendency for a positive correlation between ADG and milk yield. PMID- 27681210 TI - Head trauma on cruise ships. PMID- 27681211 TI - The metabolic syndrome among Danish seafarers: a follow-up study. AB - BACKGROUND: The metabolic syndrome (MS) represents a cluster of risk factors related to insulin resistance. Metabolic syndrome is a strong risk factor for chronic metabolic and cardiovascular diseases and is related to nutritional factors, sleep patterns, work-related stress, fatigue, and physical activity - all of which are critical issues at sea. We have previously demonstrated a MS prevalence of 24.2% in Danish seafarers. This study aimed to follow the trend of MS after 2 years' intervention. MATERIALS AND METHODS: Out of 524 Danish seafarers (mean age 37.7 years) who underwent medical fit-for-duty examination by seamen's doctors at baseline, 141 seafarers (mean age 41.3 years) were tracked and re-examined after 2 years. At baseline all participants received general advice regarding lifestyle issues. Seafarers with MS were additionally given specific advice regarding treatment. The seafarers provided questionnaire information about their workplace on board, about treatment of hyperlipidaemia, hypertension, and about previously diagnosed type 2-diabetes. In order to define MS, we collected data about waist circumference, blood pressure, triglycerides, HDL-cholesterol, and fasting plasma glucose. RESULTS: Out of 35 (26.5%) seafarers who fulfilled the criteria for MS at follow-up, 18 had MS at baseline while 9 were incident cases. Two seafarers with MS at baseline ceased to qualify for this condition at follow-up. The prevalence of seafarers with MS at follow-up represents a minimal estimate because a proportion could not be assessed due to missing fasting blood tests. Smoking and alcohol consumption was not reduced. CONCLUSIONS: In spite of the intervention, the prevalence of MS increased in this group of seafarers. This study indicates the limitations of individual health promotion and the need for corporate actions. PMID- 27681212 TI - Health status and occupational risk factors in Greek small fisheries workers. AB - BACKGROUND: Fishing is an extremely dangerous occupational activity that predisposes to occupational diseases and accidents. Greece, with about 16,000 km of coastline and its unique morphological characteristics with small islands and peninsulas, represents a strong proof of its great tradition in the fisheries sector since ancient times. The aim of the study was to examine the health status and the health risk factors present in Greek fishery workers, by exploring their working environment, thus providing a current baseline for documentation of the needs for prevention and health promotion. MATERIALS AND METHODS: An interviewer administered questionnaire was distributed in 2013 to a random sample of 172 professional small-scale fishermen of the Evros district in North-Eastern Greece. RESULTS: Eighty-eight per cent worked in coastal fisheries and 73% were using small fishing vessels, less than 10 m in length overall. Health disorders included musculoskeletal, cardiovascular and visual problems and to a minor degree by hearing, dermatologic and respiratory problems in all age groups. Seventy per cent had experienced at least one occupational accident. Heavy smoking and daily alcohol consumption was seen among nearly half of the fishermen. CONCLUSIONS: The health effects observed are causally related to the work process exposures on board and to diet, smoking, and lack of exercise. This in turn relates to the specific working conditions, the culture and level of education in small-scale fishing that need to be taken into consideration together in the prevention programmes. PMID- 27681213 TI - Occupational asthma in maritime environments: an update. AB - In 2006 we published our first review based on the available literature on occupational asthma in maritime environments in the "International Maritime Health" journal. Since then, we have obtained a great deal of new knowledge on asthma in seafood workers and fishermen and on the impact of exposures from sulphites preservatives, container fumigants etc. in maritime workers. This review aims to provide an update of the current knowledge base about occupational asthma in a maritime context and to provide recommendations regarding medical surveillance of workers at risk. PMID- 27681214 TI - Cruise ship's doctors - company employees or independent contractors? AB - Traditionally, cruise companies have stated that they are in the transport business but not in the business of providing medical services to passengers. They have claimed not to be able to supervise or control the ship's medical personnel and cruise ship's doctors have therefore mostly been signed on as independent contractors, not employees. A United States court decision from 1988, Barbetta versus S/S Bermuda Star, supported this view and ruled that a ship's owner cannot be held vicariously liable for the negligence of the ship's doctor directed at the ship's passengers. Some years ago a cruise passenger fell and hit his head while boarding a trolley ashore. Hours later he was seen aboard by the ship's doctor, who sent him to a local hospital. He died 1 week later, and his daughter filed a complaint alleging the cruise company was vicariously liable for the purported negligence of the ship's doctor and nurse, under actual or apparent agency theories. A United States district court initially dismissed the case, but in November 2014 the United States Court of Appeals for the Eleventh Circuit disagreed and reversed. From then on independently contracted ship's doctors may be considered de facto employees of the cruise line. The author discusses the employment status of physicians working on cruise ships and reviews arguments for and against the Appellate Court's decision. PMID- 27681215 TI - Head injury and anisocoria on a cruise ship. AB - A previously healthy 65-year-old female passenger presented on the 3rd day of her voyage with a small facial laceration after she fell and hit her forehead, following sudden blurred vision and dizziness. When the ship's doctor noticed that one pupil was much bigger than the other, he feared intracranial bleeding and considered helicopter evacuation. Her symptoms had started shortly after she had removed a transdermal scopolamine patch from behind her ear. Getting scopolamine from her hands in direct contact with the eye surface caused mydriasis. To prevent it, after handling the patch, the hands and the application site should have been washed thoroughly with soap and water and dried. Only time was needed for the dilated pupil to normalise. PMID- 27681216 TI - Head injury in a cruise passenger during a shore excursion. AB - A 66-year-old overweight insulin-dependent male passenger with diabetes and severe arthritis was on a 4-week circle-Pacific cruise. He fell ashore and hit his head. The ship was about to leave on a non-stop voyage - without any evacuation possibilities for the next 8 days. He was examined and had X-rays taken at the local hospital, but as his head injury was considered mild, he returned to the ship "for 48 hours of observation for signs of intracranial bleeding" - against the ship's doctor's advice. Delayed suspicion of a non displaced cervical fracture caused extra work and worries and could have, but did not complicate matters. When there are no life-saving therapy and no timely evacuation possibilities in case of deterioration, on-board observation is counterproductive. The patient should be kept in - or near - the local hospital during the necessary observation period, followed by safe repatriation. PMID- 27681217 TI - Occupational injuries and diseases among commercial fishers in Finland 1996-2015. AB - BACKGROUND: Commercial fishing is recognised as one of the most hazardous professions worldwide. In Finland, commercial fishing has some special characteristics, including fishing on ice during frozen waters, and pluriactivity of the fisher family to gain additional income. The goal of this study was to describe injury characteristics among commercial fishers in Finland during the years 1996-2015. With this information, we wish to promote creation of effective safety campaigns and interventions. MATERIALS AND METHODS: The data for this study was acquired from The Farmers' Social Insurance Institution, who handles the mandatory pension and occupational injury insurance of Finnish commercial fishers. Descriptive statistics was used to categorise and analyse the data that comprised the anonymized insurance history of 1954 insured fishers and reports on 1135 compensated injuries, 11 fatalities, and 53 occupational disease cases. RESULTS: The results show, that the injury rate of Finnish commercial fishers is high. Forty per cent of the fishing-related injuries occur aboard or when entering or leaving the vessel, while 37% happened ashore, and 11% on sea or lake ice. The most common type of incident is preceded by a slip, trip, or sway followed by a fall to lower level. The injuries result in a median disability length of 21 days. An elevated risk for Finnish (vs. Swedish) speaking, as well as for male fishers was found. The occupational diseases of the studied population were for the most part results of manual, repetitive and/or physically straining work due to e.g. hauling in fishing equipment. Due to small numbers and lack of case data, it is not possible to make any further analysis of the 11 fatalities, which were all drownings. CONCLUSIONS: Based on our findings, injury prevention should be targeted, besides preventing fatalities because of drowning, at mitigating the risks for slips, trips, and falls both aboard and ashore. PMID- 27681218 TI - The development and optimisation of a quantitative physical fitness scoring system for use amongst Naval Service personnel. AB - BACKGROUND: A lack of research currently exists in relation to the current physical fitness testing system that is used within the Irish Naval Service, not only in relation to the tests that are used but also in relation to the scores that should be achieved in order to pass the test. As such the aim of this study was to select tests for various components of physical fitness and create a scoring system that could be used to assess individuals more comprehensively. MATERIALS AND METHODS: Seventy-five individuals took part in the study (71 males, 4 females). Each participant completed a battery of physical tests analysing the following physical fitness components: flexibility, power, agility, strength, speed, anaerobic conditioning and aerobic conditioning. The mean score +/- 0.67 and +/- 1 standard deviations were used for the selection of categories. RESULTS: A six category scoring system was produced for each component of physical fitness. Scores were assigned to each category allowing a total cumulative score and an overall percentage of the total to be calculated. The categories are as follows: Score 5, Score 10, Score 15, Score 20, Score 25, Score 30. CONCLUSIONS: A quantitative scoring system has been produced that allows comprehensive physical fitness testing to be conducted. In order to achieve a complete picture of a participant's physical fitness, all tests outlined should be included in the testing process. However, the flexible nature of this system allows for tests to be included or excluded to suit the needs of an individual or organisation. The fact that the scoring system is quantitative, the time involved is relatively short, multiple participants can be tested simultaneously and the pass rates can be decided upon by the host organisation makes this system versatile and comparable across multiple jurisdictions. PMID- 27681219 TI - Prevention of sexual transmission of Zika virus. PMID- 27681220 TI - Novel insights into esophageal diagnostic procedures. AB - The 21st century offers new advances in diagnostic procedures and protocols in the management of esophageal diseases. This review highlights the most recent advances in esophageal diagnostic technologies, including clinical applications of novel endoscopic devices, such as ultrathin endoscopy and confocal laser endomicroscopy for diagnosis and management of Barrett's esophagus; novel parameters and protocols in high-resolution esophageal manometry for the identification and better classification of motility abnormalities; innovative connections between esophageal motility disorder diagnosis and detection of gastroesophageal reflux disease (GERD); impedance-pH testing for detecting the various GERD phenotypes; performance of distensibility testing for better pathophysiological knowledge of the esophagus and other gastrointestinal abnormalities; and a modern view of positron emission tomography scanning in metastatic disease detection in the era of accountability as a model for examining other new technologies. We now have better tools than ever for the detection of esophageal diseases and disorders, and emerging data are helping to define how well these tools change management and provide value to clinicians. This review features novel insights from multidisciplinary perspectives, including both surgical and medical perspectives, into these new tools, and it offers guidance on the use of novel technologies in clinical practice and future directions for research. PMID- 27681222 TI - Stereotactic radiation therapy for hepatic malignancies. AB - Management of primary and secondary tumors of the liver is a complex undertaking involving multi-disciplinary input. Radiation therapy has played a relatively marginal role in the treatment of liver tumors, but with technological innovations and the growth of the field of stereotactic body radiation therapy (SBRT), this role is evolving. In this review, I discuss the issues of radiation induced hepatic toxicity, the planning of liver SBRT treatments, clinical results with SBRT, its place amongst other non-surgical ablative treatments, and potential future avenues of investigation. PMID- 27681221 TI - Safety and efficacy of a novel diffractive lens array using a picosecond 755 nm alexandrite laser for treatment of wrinkles. AB - INTRODUCTION: Picosecond lasers have been reported to be effective for removal of tattoo pigment. This prospective study evaluated the efficacy and safety of the treatment of peri-oral and -ocular wrinkles using a novel diffractive lens array coupled with a picosecond 755 nm alexandrite laser. METHODS: Forty female subjects presenting with wrinkles from photodamage were enrolled in an IRB approved study. Subjects received four picosecond diffractive lens array treatments to the full face at 1 month intervals. Six subjects were biopsied (two subjects at 1 month, two subjects at 3 months, and two subjects at 6 months). Digital photographic images were taken at 1, 3, and 6 months post-final treatment visits. Images were graded by blinded physicians for fine lines/wrinkles, erythema, dyschromia, and global improvement. Data on discomfort level, satisfaction, and side effects were recorded. RESULTS: Overall blinded physician rated global improvement ranged from improved to much improved at 1-, 3-, and 6 month time points. At baseline the average Fitzpatrick wrinkle score was 5.48. At the 6-month follow-up the average score was 3.47. The overall average change in score from pre-treatment to post-treatment was 1.97. Subject self-assessment at 6 months indicated that 90% of subjects were extremely or satisfied with their results. Unanticipated adverse events were absent with anticipated post-treatment erythema lasting for just several hours. CONCLUSIONS: A novel diffractive lens array used with a picosecond 755 nm alexandrite laser for treatment of wrinkles is highly effective and safe for wrinkles and other signs of photoaging. Lasers Surg. Med. 49:40-44, 2017. (c) 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. PMID- 27681223 TI - Thin-Film Phase Plates for Transmission Electron Microscopy Fabricated from Metallic Glasses. AB - Thin-film phase plates (PPs) have become an interesting tool to enhance the contrast of weak-phase objects in transmission electron microscopy (TEM). The thin film usually consists of amorphous carbon, which suffers from quick degeneration under the intense electron-beam illumination. Recent investigations have focused on the search for alternative materials with an improved material stability. This work presents thin-film PPs fabricated from metallic glass alloys, which are characterized by a high electrical conductivity and an amorphous structure. Thin films of the zirconium-based alloy Zr65.0Al7.5Cu27.5 (ZAC) were fabricated and their phase-shifting properties were evaluated. The ZAC film was investigated by different TEM techniques, which reveal beneficial properties compared with amorphous carbon PPs. Particularly favorable is the small probability for inelastic plasmon scattering, which results from the combined effect of a moderate inelastic mean free path and a reduced film thickness due to a high mean inner potential. Small probability plasmon scattering improves contrast transfer at high spatial frequencies, which makes the ZAC alloy a promising material for PP fabrication. PMID- 27681224 TI - Nanofoaming to Boost the Electrochemical Performance of Ni@Ni(OH)2 Nanowires for Ultrahigh Volumetric Supercapacitors. AB - Three-dimensional free-standing film electrodes have aroused great interest for energy storage devices. However, small volumetric capacity and low operating voltage limit their practical application for large energy storage applications. Herein, a facile and novel nanofoaming process was demonstrated to boost the volumetric electrochemical capacitance of the devices via activation of Ni nanowires to form ultrathin nanosheets and porous nanostructures. The as-designed free-standing Ni@Ni(OH)2 film electrodes display a significantly enhanced volumetric capacity (462 C/cm3 at 0.5 A/cm3) and excellent cycle stability. Moreover, the as-developed hybrid supercapacitor employed Ni@Ni(OH)2 film as positive electrode and graphene-carbon nanotube film as negative electrode exhibits a high volumetric capacitance of 95 F/cm3 (at 0.25 A/cm3) and excellent cycle performance (only 14% capacitance reduction for 4500 cycles). Furthermore, the volumetric energy density can reach 33.9 mWh/cm3, which is much higher than that of most thin film lithium batteries (1-10 mWh/cm3). This work gives an insight for designing high-volume three-dimensional electrodes and paves a new way to construct binder-free film electrode for high-performance hybrid supercapacitor applications. PMID- 27681225 TI - Genetic Divergence in Eucalyptus camaldulensis Progenies in the Savanna Biome in Mato Grosso, Brazil. AB - Assessing the parental genetic differences and their subsequent prediction of progeny performance is an important first step to assure the efficiency of any breeding program. In this study, we estimate the genetic divergence in Eucalyptus camaldulensis based on the morphological traits of 132 progenies grown in a savanna biome. Thus, a field experiment was performed using a randomized block design and five replications to compare divergences in total height, commercial height, diameter at breast height, stem form and survival rate at 48 months. Tocher's clustering method was performed using the Mahalanobis and Euclidian distances. The Mahalanobis distance seemed more reliable for the assessed parameters and clustered all of the progenies into fourteen major groups. The most similar progenies (86 accessions) were clustered into Group I, while the most dissimilar (1 progeny) represented Group XIV. The divergence analysis indicated that promising crosses could be made between progenies allocated in different groups for high genetic divergence and for favorable morphological traits. PMID- 27681227 TI - Acceptability of a telecare intervention for persistent musculoskeletal pain. AB - Introduction Persistent musculoskeletal pain is a prevalent, disabling, and often undertreated condition. This paper examines the acceptability of a telecare intervention for this condition. Methods The Stepped Care to Optimize Pain Care Effectiveness (SCOPE) intervention couples automatic symptom monitoring (ASM) with optimized analgesic care management by a nurse-physician team. Data from participants in the telecare intervention arm (n = 124) of a randomized control trial of SCOPE were analysed to determine the acceptability of the telecare intervention as indicated by patient use and satisfaction. Results Most (93.5%) patients completed at least one ASM report, selecting equally web-based (49%) or interactive voice-recorded (51%) reporting. The median number of ASM reports and nurse contacts per patient was 15 and 12, respectively. Of 12 demographic and clinical factors examined, none predicted the number of ASM reports, whereas nurse contacts were more frequent in patients with higher pain severity or receiving opioids. Only a minority of ASM reports required an expedited nurse call, with the most frequent alerts being for a medication change, a nurse call or side effects. Most (92%) patients rated ASM as easy to use and found the ASM reporting (76%) and nurse contacts (81%) very or moderately helpful. Nearly three fourths of patients rated their overall pain treatment as good to excellent. The most common suggestions from patient feedback were for a free-text messaging function, more frequent nurse contact and less redundancy in ASM reporting items. Discussion Participants generally found the telecare intervention a user-friendly and helpful approach for treating persistent musculoskeletal pain. PMID- 27681226 TI - RhoA and Rac1 GTPases Differentially Regulate Agonist-Receptor Mediated Reactive Oxygen Species Generation in Platelets. AB - Agonist induced generation of reactive oxygen species (ROS) by NADPH oxidases (NOX) enhances platelet aggregation and hence the risk of thrombosis. RhoA and Rac1 GTPases are involved in ROS generation by NOX in a variety of cells, but their roles in platelet ROS production remain unclear. In this study we used platelets from RhoA and Rac1 conditional knockout mice as well as human platelets treated with Rhosin and NSC23767, rationally designed small molecule inhibitors of RhoA and Rac GTPases, respectively, to better define the contributions of RhoA and Rac1 signaling to ROS generation and platelet activation. Treatment of platelets with Rhosin inhibited: (a) U46619 induced activation of RhoA; (b) phosphorylation of p47phox, a critical component of NOX; (c) U46619 or thrombin induced ROS generation; (d) phosphorylation of myosin light chain (MLC); (e) platelet shape change; (f) platelet spreading on immobilized fibrinogen; and (g) release of P-selectin, secretion of ATP and aggregation. Conditional deletion of RhoA or Rac1 gene inhibited thrombin induced ROS generation in platelets. Addition of Y27632, a RhoA inhibitor, NSC23766 or Phox-I, an inhibitor of Rac1 p67phox interaction, to human platelets blocked thrombin induced ROS generation. These data suggest that: (a) RhoA/ROCK/p47phox signaling axis promotes ROS production that, at least in part, contributes to platelet activation in conjunction with or independent of the RhoA/ROCK mediated phosphorylation of MLC; and (b) RhoA and Rac1 differentially regulate ROS generation by inhibiting phosphorylation of p47phox and Rac1-p67phox interaction, respectively. PMID- 27681228 TI - SCOTTI: Efficient Reconstruction of Transmission within Outbreaks with the Structured Coalescent. AB - Exploiting pathogen genomes to reconstruct transmission represents a powerful tool in the fight against infectious disease. However, their interpretation rests on a number of simplifying assumptions that regularly ignore important complexities of real data, in particular within-host evolution and non-sampled patients. Here we propose a new approach to transmission inference called SCOTTI (Structured COalescent Transmission Tree Inference). This method is based on a statistical framework that models each host as a distinct population, and transmissions between hosts as migration events. Our computationally efficient implementation of this model enables the inference of host-to-host transmission while accommodating within-host evolution and non-sampled hosts. SCOTTI is distributed as an open source package for the phylogenetic software BEAST2. We show that SCOTTI can generally infer transmission events even in the presence of considerable within-host variation, can account for the uncertainty associated with the possible presence of non-sampled hosts, and can efficiently use data from multiple samples of the same host, although there is some reduction in accuracy when samples are collected very close to the infection time. We illustrate the features of our approach by investigating transmission from genetic and epidemiological data in a Foot and Mouth Disease Virus (FMDV) veterinary outbreak in England and a Klebsiella pneumoniae outbreak in a Nepali neonatal unit. Transmission histories inferred with SCOTTI will be important in devising effective measures to prevent and halt transmission. PMID- 27681229 TI - Equity in the utilization of physician and inpatient hospital services: evidence from Korean health panel survey. AB - BACKGROUND: Little is known regarding equity in health care utilization among Koreans since 2008. This study examines the extent to which equity in the use of health care services has been achieved in Korea. METHODS: Descriptive and logistic regression analysis was performed. The sample for this study was 17,035 individuals who participated in interviews. RESULTS: Differences in need substantially account for the original differences observed between subgroups of Koreans. Need factors were important determinants of Koreans using physician and inpatient hospital services. Having income did not ameliorate the subgroup differences in the use of physician services. Nonetheless, having income remains an important predictor of physician utilization. CONCLUSIONS: The Korean health care system does not yield a fully equitable distribution of physician and inpatient hospital services. Health care reforms in Korea should continue to concentrate on insuring effective universal health care, implying that all population groups with need receive effective coverage. PMID- 27681230 TI - Weight and weight changes throughout life and postmenopausal breast cancer risk: a case-control study in France. AB - BACKGROUND: Overweight and weight gain throughout adult life have been associated with increased risk of breast cancer after the menopause. However the role of body weight at a young age and of the timing of weight gain over the lifetime in postmenopausal breast cancer is not well documented. METHODS: We conducted a population-based case-control study on breast cancer in France that included 739 cases and 815 population controls in postmenopausal women. Height, weight at age 20, 40 and 50 as well as weight one year before diagnosis were obtained during in person interviews. RESULTS: No association between body mass index at the age of 20 years and breast cancer after the menopause was detected. However, we found that postmenopausal breast cancer was associated with weight gain between ages 40 and 50 years (OR per 5 kg/m2 increase in BMI: 1.45 [95%ci 1.06-1.98]). The increased risk of breast cancer associated with weight gain was more consistent in leaner women at age 20, in older postmenopausal women (>65 years), and in women who did not use menopausal hormone therapy. CONCLUSIONS: These findings point to the importance of controlling for weight gain in middle aged-women. The role of low body weight in young adulthood in breast cancer risk after the menopause should be further scrutinized. PMID- 27681231 TI - Texture analysis of parotid gland as a predictive factor of radiation induced xerostomia: A subset analysis. PMID- 27681232 TI - Genome sequence of the filamentous soil fungus Chaetomium cochliodes reveals abundance of genes for heme enzymes from all peroxidase and catalase superfamilies. AB - BACKGROUND: The ascomycetous family Chaetomiaceae (class Sordariomycetes) includes numerous soilborn, saprophytic, endophytic and pathogenic fungi which can adapt to various growth conditions and living niches by providing a broad armory of oxidative and antioxidant enzymes. RESULTS: We release the 34.7 Mbp draft genome of Chaetomium cochliodes CCM F-232 consisting of 6036 contigs with an average size of 5756 bp and reconstructed its phylogeny. We show that this filamentous fungus is closely related but not identical to Chaetomium globosum and Chaetomium elatum. We screened and critically analysed this genome for open reading frames coding for essential antioxidant enzymes. It is demonstrated that the genome of C. cochliodes contains genes encoding putative enzymes from all four known heme peroxidase superfamilies including bifunctional catalase peroxidase (KatG), cytochrome c peroxidase (CcP), manganese peroxidase, two paralogs of hybrid B peroxidases (HyBpox), cyclooxygenase, linoleate diol synthase, dye-decolorizing peroxidase (DyP) of type B and three paralogs of heme thiolate peroxidases. Both KatG and DyP-type B are shown to be introduced into ascomycetes genomes by horizontal gene transfer from various bacteria. In addition, two putative large subunit secretory and two small-subunit typical catalases are found in C. cochliodes. We support our genomic findings with quantitative transcription analysis of nine peroxidase & catalase genes. CONCLUSIONS: We delineate molecular phylogeny of five distinct gene superfamilies coding for essential heme oxidoreductases in Chaetomia and from the transcription analysis the role of this antioxidant enzymatic armory for the survival of a peculiar soil ascomycete in various harsh environments. PMID- 27681234 TI - Thoracic empyema caused by Campylobacter rectus. AB - We report a case of thoracic empyema caused by Campylobacter rectus, an organism considered as a periodontal pathogen but rarely recovered from extraoral specimens. The patient fully recovered through drainage of purulent pleural fluid and administration of antibiotics. The present case illustrates that C. rectus can be a cause of not only periodontal disease but also pulmonary infection. PMID- 27681233 TI - Vancomycin-associated Henoch-Schonlein purpura. AB - Intravenous vancomycin is a widely used antibiotics, but it causes different types of cutaneous hypersensitivity reactions, ranging from maculopapular rash, red-man syndrome, drug rash with eosinophilia and systemic symptoms, IgA bullous dermatosis, leukocytoclastic vasculitis, Stevens-Johnsons syndrome, to IgE mediated anaphylaxis. We report an elderly patient with the end-stage renal disease presented with diffuse palpable purpura while receiving IV vancomycin therapy for methicillin-resistant Staphylococcus aureus septicemia. Histopathology of skin biopsy revealed perivascular infiltrates of leukocytoclastic debris with necrosis of the small-sized blood vessels. Direct immunofluorescence analysis demonstrated vivid IgA plus C3 immune-complex deposits localized to the vessel walls, and no immune complexes were noted on the dermoepidermal junction. There was no IgG or IgM immunoreactivity detected on the tissue specimen. Rheumatologic disease work-ups were negative. A diagnosis of vancomycin-associated Henoch-Schonlein variant of vasculitis was made. Vancomycin was substituted by daptomycin, and the purpuric skin rashes were resolved. Since vancomycin is a commonly used antibacterial agent, clinicians are encouraged to have a heightened awareness of this rare adverse skin reaction. Early recognition and prompt discontinuation of the medication is the key in management. As it is not an Ig-E mediated reaction, desensitization of vancomycin or re-challenge with vancomycin is not recommended as re-exposure to the drug may result in a recurrence of similar manifestations with potential permanent renal failure. PMID- 27681236 TI - Structural Variation Detection with Read Pair Information: An Improved Null Hypothesis Reduces Bias. AB - Reads from paired-end and mate-pair libraries are often utilized to find structural variation in genomes, and one common approach is to use their fragment length for detection. After aligning read pairs to the reference, read pair distances are analyzed for statistically significant deviations. However, previously proposed methods are based on a simplified model of observed fragment lengths that does not agree with data. We show how this model limits statistical analysis of identifying variants and propose a new model by adapting a model we have previously introduced for contig scaffolding, which agrees with data. From this model, we derive an improved null hypothesis that when applied in the variant caller CLEVER, reduces the number of false positives and corrects a bias that contributes to more deletion calls than insertion calls. We advise developers of variant callers with statistical fragment length-based methods to adapt the concepts in our proposed model and null hypothesis. PMID- 27681235 TI - Case-control study of pneumonia patients with Streptococcus anginosus group bacteria in their sputum. AB - BACKGROUND AND OBJECTIVE: In recent years, Streptococcus anginosus group (SAG) bacteria are becoming increasingly recognized as important pneumonia-causing pathogens. Although several small studies have been reported, the features of SAG pneumonia remain unclear, because the identification of SAG from sputum cultures is not routinely performed in most microbiology laboratories. The aim of this study was to elucidate the clinical characteristics of SAG pneumonia. PATIENT AND METHODS: This was a retrospective case-control study utilizing data obtained in our hospital between September 2009 and June 2016. We investigated 31 patients with SAG pneumonia (PWP), and also assessed the difference between the 31 PWP and 37 patients without pneumonia (PWOP) in whose sputum SAG was detected. RESULTS: Seventy-one percent of the patients were men and the median age was 78 years in the PWP. Univariate analysis indicated that the PWP were significantly more often a bed-ridden (p < 0.01) with comorbid aspiration than were the PWOP (p < 0.05). Among the PWP, nursing and healthcare-associated pneumonia (NHCAP) was the more common type of pneumonia (54.8%). S. anginosus was detected significantly more frequently in sputum cultures of PWP than PWOP (p < 0.01), and multiple pathogens were detected more frequently in PWP (p < 0.01). Streptococcus constellatus was the most frequently detected pathogen in patients with a single bacterial infection. Empyema was observed only in patients with multiple bacteria. CONCLUSIONS: SAG should be recognized as important causative pathogens of pneumonia, particularly among elderly patients with underlying disease associated with aspiration. NHCAP was the more common type of SAG pneumonia in this study. PMID- 27681238 TI - Erratum to: Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases. PMID- 27681237 TI - Long noncoding RNA (lincRNA), a new paradigm in gene expression control. AB - Long intergenic non-coding RNAs (lincRNAs) are defined as RNA transcripts that are longer than 200 nucleotides. By definition, these RNAs must not have open reading frames that encode proteins. Many of these transcripts are encoded by RNA polymerase II, are spliced, and are poly-adenylated. This final fact indicates that there is a trove of information about lincRNAs in databases such as the Gene Expression Omnibus (GEO), which is a repository for RNAseq and microarray data. Recent experiments indicate that there are upwards of 15,000 lincRNAs encoded by the human genome. The term "intergenic" refers to the identification of these transcripts from regions of the genome that do not contain protein-encoding genes. These regions coincide with what was once labeled as the "junk DNA" portions of our genomes, which, upon careful examination by whole genome RNA sequencing experiments, clearly encode RNA transcripts. LincRNAs also contain promoter- or enhancer-associated RNAs that are gene proximal and can be either in the sense or antisense orientation, relative to the protein-coding gene with which they are associated. In this review, we describe the functions of lincRNAs playing roles in biological processes such as gene expression control, scaffold formation, and epigenetic control. PMID- 27681239 TI - Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi targeted directed compounds against Alzheimer's disease. AB - This paper describes the synthesis and evaluation of new dihydropyrimidinone (DHPM)-derived selenoesters as potential multi-targeted agents for the treatment of Alzheimer's disease. A series of DHPM-derived selenoesters were obtained with high structural diversity through a short and modular synthetic route. The antioxidant activity was evaluated by TBARS and iron chelation assays. These compounds were also evaluated as acetylcholinesterase inhibitors (AChEi). The compounds demonstrated good antioxidant activity, since they presented excellent lipid peroxidation inhibition and good iron chelation activity. In addition, they showed acetylcholinesterase inhibition activity and some of them presented activity superior to that of the standard drug galantamine. The in silico predictions showed that the compound 1h may present a good pharmacokinetic profile. Therefore, the series of DHPM-derived selenoesters described herein displayed good potential for the development of antioxidant and anticholinesterasic agents in the search for new multi-targeted therapeutics for the treatment of Alzheimer's disease. PMID- 27681240 TI - (1S,2E,4S,7E,11E)-2,7,11-Cembratriene-4,6-diol semisynthetic analogs as novel c Met inhibitors for the control of c-Met-dependent breast malignancies. AB - (1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) and its 4-epi-analog (2) are the cembranoid precursors to several key flavor ingredients in most Nicotiana (tobacco) species. Nearly 40-60% of 1 and 2 are purposely degraded during the commercial tobacco fermentation. However, 1 and 2 display promising bioactivities, including anticancer. Breast cancer is the most diagnosed cancer in women and ranked second female disease killer. The receptor tyrosine kinase c Met correlates with aggressiveness of certain breast cancer phenotypes and thus considered a valid therapeutic target. This study reports the discovery and optimization of the tobacco-based cembranoid 1 as a novel c-Met inhibitory scaffold using combined structure- and ligand-based approaches. 1 displayed antiproliferative, anti-migratory and anti-invasive effects against the c-Met overexpressing MDA-MB-231 breast cancer cells at moderate MUM concentrations. The Z'-LYTE kinase platform and Western blot analysis identified c-Met as a potential macromolecular target. Rationally designed carbamate analogs were proposed to probe additional targeted c-Met interactions and improve the cellular potency. The 6-phenyl carbamate 3 showed enhanced c-Met inhibitory activity. Structure activity relationships of different substituents on the 3's phenyl moiety were studied. The most active analog 20 showed potent in vitro anticancer activity against the MDA-MB-231 breast cancer cells at low MUM concentrations, with minimal toxicity on the non-tumorigenic MCF-10A mammary epithelial cells. Cembranoid 20 potently inhibited the c-Met catalytic activity in Z'-LYTE kinase assay and various cellular c-Met-driven signaling pathways. Furthermore, 20 displayed a robust antitumor activity in a breast cancer xenograft athymic mouse model and thus promoted to the lead rank. Cembranoids are novel c-Met inhibitors appropriate for future use to control c-Met dependent malignancies. PMID- 27681243 TI - Epigenome and exposome in prenatal programming: essential components of personalized medicine in need of understanding and development. PMID- 27681241 TI - High-intensity interval training: a review of its impact on glucose control and cardiometabolic health. AB - Exercise plays a central role in the management and treatment of common metabolic diseases, but modern society presents many barriers to exercise. Over the past decade there has been considerable interest surrounding high-intensity interval training (HIIT), with advocates claiming it can induce health benefits of similar, if not superior magnitude to moderate-intensity continuous exercise, despite reduced time commitment. As the safety of HIIT becomes clearer, focus has shifted away from using HIIT in healthy individuals towards using this form of training in clinical populations. The continued growth of metabolic disease and reduced physical activity presents a global health challenge and effective therapies are urgently required. The aim of this review is to explore whether the acclaim surrounding HIIT is justified by examining the effect of HIIT on glucose control, its ability to affect cardiovascular function and the underlying mechanisms of the changes observed in those with common metabolic diseases. It also explores translation of the research into clinical practice. PMID- 27681242 TI - Context-dependent memory following recurrent hypoglycaemia in non-diabetic rats is mediated via glucocorticoid signalling in the dorsal hippocampus. AB - AIMS/HYPOTHESIS: Recurrent hypoglycaemia is primarily caused by repeated over administration of insulin to patients with diabetes. Although cognition is impaired during hypoglycaemia, restoration of euglycaemia after recurrent hypoglycaemia is associated with improved hippocampally mediated memory. Recurrent hypoglycaemia alters glucocorticoid secretion in response to hypoglycaemia; glucocorticoids are well established to regulate hippocampal processes, suggesting a possible mechanism for recurrent hypoglycaemia modulation of subsequent cognition. We tested the hypothesis that glucocorticoids within the dorsal hippocampus might mediate the impact of recurrent hypoglycaemia on hippocampal cognitive processes. METHODS: We characterised changes in the dorsal hippocampus at several time points to identify specific mechanisms affected by recurrent hypoglycaemia, using a well-validated 3 day model of recurrent hypoglycaemia either alone or with intrahippocampal delivery of glucocorticoid (mifepristone) and mineralocorticoid (spironolactone) receptor antagonists prior to each hypoglycaemic episode. RESULTS: Recurrent hypoglycaemia enhanced learning and also increased hippocampal expression of glucocorticoid receptors, serum/glucocorticoid-regulated kinase 1, cyclic AMP response element binding (CREB) phosphorylation, and plasma membrane levels of alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors. Both hippocampus-dependent memory enhancement and the molecular changes were reversed by glucocorticoid receptor antagonist treatment. CONCLUSIONS/INTERPRETATION: These results indicate that increased glucocorticoid signalling during recurrent hypoglycaemia produces several changes in the dorsal hippocampus that are conducive to enhanced hippocampus-dependent contextual learning. These changes appear to be adaptive, and in addition to supporting cognition may reduce damage otherwise caused by repeated exposure to severe hypoglycaemia. PMID- 27681244 TI - Uric acid and essential hypertension: the endothelial connection. PMID- 27681245 TI - Ambulatory blood pressure monitoring: a mandatory approach in high-risk pregnancy? PMID- 27681246 TI - The importance of not overlooking curable hypertension: primary aldosteronism rarely screened for reflecting poor uptake of Endocrine Society Guidelines. PMID- 27681247 TI - Restenosis of renal artery fibromuscular dysplasia after percutaneous angioplasty. PMID- 27681248 TI - Reply. PMID- 27681249 TI - 'Another easily recognizable atrial abnormality and risk of stroke in patients in sinus rhythm. PMID- 27681250 TI - In vitro alpha-glucosidase inhibitory activity of isolated fractions from water extract of Qingzhuan dark tea. AB - BACKGROUND: Natural products have being used as potential inhibitors against carbohydrate-hydrolyzing enzymes to treat diabetes mellitus. Chinese dark tea has various interesting bioactivities. In this study, the active compounds from Qingzhuan dark tea were separated and their anti-diabetic activity was examined using an in vitro enzymatic model. METHODS: The chloroform, ethyl acetate, n butanol, sediment and residual aqua fractions of a Chinese dark tea (Qingzhuan tea) were prepared by successively isolating the water extract with different solvents and their in vitro inhibitory activities against alpha-glucosidase were assessed. The fraction with the highest inhibitory activity was further characterized to obtain the main active components of Qingzhuan tea. RESULTS: The ethyl acetate fraction had the greatest inhibitory effect on alpha-glucosidase, followed by n-butanol, sediment and residual aqua fractions (with the IC50 values of 0.26 mg/mL, 2.94 mg/mL, 3.02 mg/mL, and 5.24 mg/mL, respectively), mainly due to the high content of polyphenols. Among the eight subfractions (QEF1-8) isolated from the ethyl acetate fraction, QEF8 fraction showed the highest alpha glucosidase inhibitory potential in a competitive inhibitory manner (the K i value of 77.10 MUg/mL). HPLC-MS analysis revealed that (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) were the predominant active components in QEF8. CONCLUSION: These results indicated that Qingzhuan tea extracts exerted potent inhibitory effects against alpha-glucosidase, EGCG and ECG were likely responsible for the inhibitory activity in Qingzhuan tea. Qingzhuan tea may be recommended as an oral antidiabetic diet. PMID- 27681252 TI - Is bioresorbable vascular scaffold acute recoil affected by baseline renal function and scaffold selection? AB - OBJECTIVE: The aim of the present study was to investigate the relationship between glomerular filtration rate (GFR) and acute post-scaffold recoil (PSR) in patients undergoing bioresorbable scaffold (BVS) implantation. METHODS: We included 130 patients who underwent everolimus-eluting BVS device (Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) or the novolimus-eluting BVS device (Elixir Medical Corporation) implantations for single or multi-vessel disease. Clinical, angiographic variables and procedural characteristics were defined and pre-procedural GFR was calculated for each patient. Post-procedural angiographic parameters of each patient were analyzed. Primary objective of the study was to evaluate the effect of GFR on angiographic outcomes after BVS implantation while secondary objective was to compare post-procedural angiographic results between the two BVS device groups. RESULTS: Baseline clinical characteristics and angiographic parameters were similar between the two BVS groups. Post-procedural angiographic analysis revealed significantly lower PSR in the DESolve group than the Absorb group (0.10+/-0.04 vs. 0.13+/-0.05, p: 0.003). When PSR in the whole study population was evaluated, it was positively correlated with age, tortuosity , calcification and PBR as there was a negative correlation between GFR. Besides GFR were found to be independent predictors for PSR in all groups and the whole study population. CONCLUSION: In patients undergoing BVS implantation, pre procedural low GFR is associated with increased post-procedural PSR. Calcification, age, PBR, dyslipidemia and tortuosity are other independent risk factors for PSR. DESolve has lower PSR when compared with Absorb. PMID- 27681251 TI - Restenosis after percutaneous coronary intervention for coronary chronic total occlusion. The central role of an optimized immediate post-procedural angiographic result. AB - BACKGROUND: Factors of restenosis after percutaneous coronary intervention (PCI) for chronic total coronary occlusion (CTO) have not been fully explored. In particular, although the last ACC/AHA guidelines on PCI suggest that a minimum diameter stenosis of 10% with an optimal goal of as close to 0% as possible should be the new benchmark for lesions treated by stenting, angiographic success of PCI for CTO remains in the literature most often defined as a <30% residual diameter stenosis. Whether an optimized immediate post-PCI angiographic result (OAR) defined by a minimal diameter stenosis as close to 0% is associated with a lower restenosis rate in this subset of coronary lesions remains unknown. METHODS: Therefore, we assessed by quantitative coronary analysis (QCA) both the immediate post-PCI and 6-month follow-up angiographic results of 170 successfully treated true CTO. RESULTS: Post-PCI QCA immediate residual diameter stenosis was <30% in all 170 CTOs and OAR defined as a <=10% residual stenosis was achieved in 133 (78%). Global binary restenosis rate was 21% in the 170 lesions. Restenosis rates were 46% and 14% in the non-OAR group and in the OAR group, respectively (p<0.0001). Multivariate analysis showed that a non-OAR, a younger age and a retrograde approach were independent factors of restenosis. CONCLUSION: Thus, an optimized immediate angiographic result with a minimal diameter stenosis as close to 0% as possible appears to be associated with a lower rate of restenosis after CTO PCI. PMID- 27681253 TI - Genome-wide identification and expression analysis of stress-associated proteins (SAPs) containing A20/AN1 zinc finger in cotton. AB - Stress-associated proteins (SAPs) containing the A20/AN1 zinc-finger domain play important roles in response to both biotic and abiotic stresses in plants. Nevertheless, few studies have focused on the SAP gene family in cotton. To explore the distributions and expression patterns of these genes, we performed genome-wide identification and characterization of SAPs in tetraploid Gossypium hirsutum L. TM-1 (AD1). A total of 37 genes encoding SAPs were identified, 36 of which were duplicated in the A and D sub-genomes. The analysis of gene architectures and conserved protein motifs revealed that nearly all A20-AN1-type SAPs were intron-free, whereas AN1-AN1-type SAPs contained one intron. The cis elements of the SAP promoters were studied, as were the expression levels of cotton SAP genes under different stresses based on RNA-seq data and validated by qRT-PCR. Most cotton SAP genes were induced by multiple stresses and phytohormones, particularly salt stress, indicating that SAP genes may play important roles in cotton's response to unfavorable environmental changes. Among these identified SAPs, the expression of GhSAP17A/D is suppressed in cotton response to Vertillium dahliae, and the GhSAP17A/D-silenced cotton exhibits more resistance to V. dahliae. This study provides insight into the evolution of SAP genes in upland cotton and may aid in efforts at further functional identification of A20/AN1-type proteins and cotton's response to different stresses. PMID- 27681255 TI - Investigation of the leaching behavior of lead in stabilized/solidified waste using a two-year semi-dynamic leaching test. AB - Long-term leaching behavior of contaminant from stabilization/solidification (S/S) treated waste stays unclear. For the purpose of studying long-term leaching behavior and leaching mechanism of lead from cement stabilized soil under different pH environment, semi-dynamic leaching test was extended to two years to investigate leaching behaviors of S/S treated lead contaminated soil. Effectiveness of S/S treatment in different scenarios was evaluated by leachability index (LX) and effective diffusion coefficient (De). In addition, the long-term leaching mechanism was investigated at different leaching periods. Results showed that no significant difference was observed among the values of the cumulative release of Pb, De and LX in weakly alkaline and weakly acidic environment (pH value varied from 5.00 to 10.00), and all the controlling leaching mechanisms of the samples immersed in weakly alkaline and weakly acidic environments turned out to be diffusion. Strong acid environment would significantly affect the leaching behavior and leaching mechanism of lead from S/S monolith. The two-year variation of De appeared to be time dependent, and De values increased after the 210th day in weakly alkaline and weakly acidic environment. PMID- 27681254 TI - Differentially expressed microRNAs in the corpus cavernosum from a murine model with type 2 diabetes mellitus-associated erectile dysfunction. AB - To better understand the molecular aetiology of type 2 diabetes mellitus associated erectile dysfunction (T2DMED) and to provide candidates for further study of its diagnosis and treatment, this study was designed to investigate differentially expressed microRNAs (miRNAs) in the corpus cavernosum (CC) of mice with T2DMED using GeneChip array techniques (Affymetrix miRNA 4.0 Array) and to predict target genes and signalling pathways regulated by these miRNAs based on bioinformatic analysis using TargetScan, the DAIAN web platform and DAVID. In the initial screening, 21 miRNAs appeared distinctly expressed in the T2DMED group (fold change >=3, p <= 0.01). Among them, the differential expression of miR-18a, miR-206, miR-122, and miR-133 were confirmed by qRT-PCR (p < 0.05 and FDR <5 %). According to bioinformatic analysis, the four miRNAs were speculated to play potential roles in the mechanisms of T2DMED via regulating 28 different genes and several pathways, including apoptosis, fibrosis, eNOS/cGMP/PKG, and vascular smooth muscle contraction processes, which mainly focused on influencing the functions of the endothelium and smooth muscle in the CC. IGF-1, as one of the target genes, was verified to decrease in the CCs of T2DMED animals via ELISA and was confirmed as the target of miR-18a or miR-206 via luciferase assay. Finally, these four miRNAs deserve further confirmation as biomarkers of T2DMED in larger studies. Additionally, miR-18a and/or miR-206 may provide new preventive/therapeutic targets for ED management by targeting IGF-1. PMID- 27681256 TI - Disposal options for polluted plants grown on heavy metal contaminated brownfield lands - A review. AB - Reducing or preventing damage caused by environmental pollution is a significant goal nowadays. Phytoextraction, as remediation technique is widely used, but during the process, the heavy metal content of the biomass grown on these sites special treatment and disposal techniques are required, for example liquid extraction, direct disposal, composting, and combustion. These processes are discussed in this review in economical and environmental aspects. The following main properties are analyzed: form and harmful element content of remains, utilization of the main and byproducts, affect to the environment during the treatment and disposal. The thermal treatment (combustion, gasification) of contaminated biomass provides a promising alternative disposal option, because the energy production affects the rate of return, and the harmful elements are riched in a small amount of solid remains depending on the ash content of the plant (1-2%). The biomass combustion technology is a wildely used energy production process in residential and industrial scale, but the ordinary biomass firing systems are not suited to burn this type of fuel without environmental risk. PMID- 27681257 TI - New magnetic graphene-based inorganic-organic sol-gel hybrid nanocomposite for simultaneous analysis of polar and non-polar organophosphorus pesticides from water samples using solid-phase extraction. AB - A new graphene-based tetraethoxysilane-methyltrimethoxysilane sol-gel hybrid magnetic nanocomposite (Fe3O4@G-TEOS-MTMOS) was synthesised, characterized and successfully applied in magnetic solid-phase extraction (MSPE) for simultaneous analysis of polar and non-polar organophosphorus pesticides from several water samples. The Fe3O4@G-TEOS-MTMOS nanocomposite was characterized using Fourier transform-infrared spectroscopy, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy and X-ray diffraction. Separation, determination and quantification were achieved using gas chromatography coupled with micro electron capture detector. Adsorption capacity of the sorbent was calculated using Langmuir equation. MSPE was linear in the range 100-1000 pg mL-1 for phosphamidon and dimethoate, and 10-100 pg mL-1 for chlorpyrifos and diazinon, with limit of detection (S/N = 3) of 19.8, 23.7, 1.4 and 2.9 pg mL-1 for phosphamidon, dimethoate, diazinon and chlorpyrifos, respectively. The LODs obtained is well below the maximum residual level (100 pg mL-1) as set by European Union for pesticides in drinking water. Acceptable precision (%RSD) was achieved for intra-day (1.3-8.7%, n = 3) and inter-day (7.6-17.8%, n = 15) analyses. Fe3O4@G-TEOS-MTMOS showed high adsorption capacity (54.4-76.3 mg g-1) for the selected OPPs. No pesticide residues were detected in the water samples analysed. Excellent extraction recoveries (83-105%) were obtained for the spiked OPPs from tap, river, lake and sea water samples. The newly synthesised Fe3O4@G TEOS-MTMOS showed high potential as adsorbent for OPPs analysis. PMID- 27681258 TI - A simulation study of inorganic sulfur cycling in the water level fluctuation zone of the Three Gorges Reservoir, China and the implications for mercury methylation. AB - The water level fluctuation zone (WLFZ) of the Three Gorges Reservoir (TGR) in China experiences a drying and wetting rotation every year, and the water level induced redox variation may influence inorganic sulfur speciation and mercury methylation. In this work, a simulative flooding and drying experiment and a sulfate added flooding experiment were conducted to study this topic. The results showed that sulfate was reduced from the 10th d during the flooding period based on the detected sulfide in water and the increased elemental sulfur (S0) in sediment. Sulfate reduction and sulfide re-oxidation led to the increase of S0 contents with the maximal values of 1.86 and 0.46 mg kg-1 during the flooding and drying period, respectively. Methylmercury (MeHg) content in sediment displayed a rising trend (0.16-0.28 MUg kg-1) in the first 40 d during the flooding period, and then declined from 0.28 to 0.15 MUg kg-1. A positive correlation between MeHg content and S0 content in soil (r = 0.53, p < 0.05) was found during the flooding period, and a positive but not significant correlation between the percent of MeHg in THg (%MeHg) and S0 content (r = 0.85, p = 0.08). In sulfate added flooding simulation, MeHg content in sediment did not increase with the sulfate concentration increasing. The increased pyrite in high-sulfate treatment may fix mercury through adsorption process. This study demonstrated that inorganic sulfur species especially S0 and chromium reducible sulfur (CRS) play an important role on mercury methylation in the WLFZ of the TGR. PMID- 27681259 TI - Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis. AB - BACKGROUND: Anaemia affects 60-80 % of patients admitted to intensive care units (ICUs). Allogeneic red blood cell (RBC) transfusions remain the mainstay of treatment for anaemia but are associated with risks and are costly. Our objective was to assess the efficacy and safety of iron supplementation by any route, in anaemic patients in adult ICUs. METHODS: Electronic databases (CENTRAL, MEDLINE, EMBASE) were searched through March 2016 for randomized controlled trials (RCT)s comparing iron by any route with placebo/no iron. Primary outcomes were red blood cell transfusions and mean haemoglobin concentration. Secondary outcomes included mortality, infection, ICU and hospital length of stay, mean difference (MD) in iron biomarkers, health-related quality of life and adverse events. RESULTS: Five RCTs recruiting 665 patients met the inclusion criteria; intravenous iron was tested in four of the RCTs. There was no difference in allogeneic RBC transfusion requirements (relative risk 0.87, 95 % confidence interval (CI) 0.70 to 1.07, p = 0.18, five trials) or mean number of RBC units transfused (MD -0.45, 95 % CI 1.34 to 0.43, p = 0.32, two trials) in patients receiving or not receiving iron. Similarly, there was no difference between groups in haemoglobin at short-term (up to 10 days) (MD -0.25, 95 % CI -0.79 to 0.28, p = 0.35, three trials) or mid term follow up (last measured time point in hospital or end of trial) (MD 0.21, 95 % CI -0.13 to 0.55, p = 0.23, three trials). There was no difference in secondary outcomes of mortality, in-hospital infection, or length of stay. Risk of bias was generally low although three trials had high risk of attrition bias; only one trial had low risk of bias across all domains. CONCLUSION: Iron supplementation does not reduce RBC transfusion requirements in critically ill adults, but there is considerable heterogeneity between trials in study design, nature of interventions, and outcomes. Well-designed trials are needed to investigate the optimal iron dosing regimens and strategies to identify which patients are most likely to benefit from iron, together with patient-focused outcomes. TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews CRD42015016627 . Registered 2 March 2015. PMID- 27681260 TI - Simultaneous recording of EEG and fNIRS during visuo-spatial and facial expression processing in a dual task paradigm. AB - Emotional processing is probably the most crucial tool for orienting oneself in our everyday social life and has been considered to be highly automatic for a long time. Dual task (DT) research shows that information competing for working memory resources impairs the identification of emotional facial expressions. Effects of cognitive load in DT paradigms have been confirmed in numerous neuroimaging studies. However, interference occurring during a DT comprised of decoding emotional facial expressions and a visuo-spatial working memory task has yet to be visualized. To investigate the DT interference effect on brain areas associated not only with working memory, but also emotional and visuo-spatial processing, we recorded brain activation within the prefrontal cortex and parietal-occipital sensory areas using functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) simultaneously. Our study consisted of N = 36 participants (27 female) performing the following tasks: a) Corsi blocks, b) identification of emotional facial expressions or c) DT comprising of tasks a) and b). We predicted higher activation of the prefrontal cortex during DT and corresponding reduced P100 and P300 amplitudes. As expected, fNIRS measurements revealed significantly higher neuronal activation within the prefrontal cortex in the DT condition. When comparing DT to the single tasks, the P100 amplitude was reduced, but the P300 amplitude did not show the expected reduction. Our findings underline that at least some aspects of emotional processing are not entirely automatic, but depend on prefrontal control and are therefore affected by cognitive load, in particular visuo-spatial working memory resources. PMID- 27681262 TI - Slowing the Tide of Alcohol Use Disorders. AB - Alcohol use disorders (AUDs)-a spectrum including at-risk drinking, alcohol abuse, dependence, and addiction-is a highly prevalent problem worldwide with a substantial economic impact. The toll of alcohol on individual health and healthcare systems is devastating. Alcohol is estimated to be the fifth leading risk factor for global disability-adjusted life years. Tackling the problem of AUD requires a comprehensive strategy that includes solid action on price, availability, and marketing of alcohol. Restricting or banning alcohol advertising may reduce exposure to the risk posed by alcohol at the individual and general population level. Warning labels about the cancer risks associated with drinking have a high degree of public support and may be an inexpensive and acceptable way to educate the public. Religiosity may reduce risk behaviors and contribute to health decision making related to alcohol use. PMID- 27681261 TI - Survey on the Effectiveness of Dietary Supplements to Treat Tinnitus. AB - PURPOSE: We surveyed the benefit of dietary supplements to treat tinnitus and reported adverse effects. METHOD: A website was created for people with tinnitus to complete a variety of questions. RESULTS: The 1,788 subjects who responded to questionnaires came from 53 different countries; 413 (23.1%) reported taking supplements. No effect on tinnitus was reported in 70.7%, improvement in 19.0%, and worsening in 10.3%. Adverse effects were reported in 6% (n = 36), including bleeding, diarrhea, headache, and others. Supplements were reported to be helpful for sleep: melatonin (effect size, d = 1.228) and lipoflavonoid (d = 0.5244); emotional reactions: melatonin (d = 0.6138) and lipoflavonoid (d = 0.457); hearing: Ginkgo biloba (d = 0.3758); and concentration Ginkgo biloba (d = 0.3611). The positive, subjective reports should be interpreted cautiously; many might have reported a positive effect because they were committed to treatment and expected a benefit. Users of supplements were more likely to have loudness hyperacusis and to have a louder tinnitus. CONCLUSIONS: The use of dietary supplements to treat tinnitus is common, particularly with Ginkgo biloba, lipoflavonoids, magnesium, melatonin, vitamin B12, and zinc. It is likely that some supplements will help with sleep for some patients. However, they are generally not effective, and many produced adverse effects. We concluded that dietary supplements should not be recommended to treat tinnitus but could have a positive outcome on tinnitus reactions in some people. PMID- 27681263 TI - Commitment to Celibacy in German Catholic Priests: Its Relation to Religious Practices, Psychosomatic Health and Psychosocial Resources. AB - We aimed to investigate Catholic priests' commitment to celibacy and its relation to their religious practices, life and work satisfaction, and psychosomatic health. Results of our cross-sectional study of 2549 priests show that the majority finds living in celibacy helpful to minister more effectively. Nevertheless, a large proportion see it as a burden and would not choose celibate life again. Commitment to celibacy was predicted best by the frequency of religious practices (liturgy), work engagement and personal relation with God, explaining 39 % of variance. These resources are predictors for maintaining a celibate lifestyle and facilitate priests' satisfaction with life and commitment to their ministry. PMID- 27681264 TI - Targeting IFN-lambda: therapeutic implications. AB - INTRODUCTION: Type-III interferons (IFN-lambda), the most recently discovered family of IFNs, shares common features with other family members, but also has many distinctive activities. IFN-lambda uniquely has a different receptor complex, and a more focused pattern of tissue expression and signaling effects, from other classes of IFNs. Multiple genome-wide association studies (GWAS) and subsequent validation reports suggest a pivotal role for polymorphisms near the IFNL3 gene in hepatitis C clearance and control, as also for several other epithelial cell tropic viruses. Apart from its antiviral activity, IFN-lambda possesses anti-tumor, immune-inflammatory and homeostatic functions. The overlapping effects of IFN-lambda with type I IFN, with a restricted tissue expression pattern renders IFN-lambda an attractive therapeutic target for viral infection, cancer and autoimmune diseases, with limited side effects. Areas covered: This review will summarize the current and future therapeutic opportunities offered by this most recently discovered family of interferons. Expert opinion: Our knowledge on IFN-lambda is rapidly expanding. Though there are many remaining questions and challenges that require elucidation, the unique characteristics of IFN-lambda increases enthusiasm that multiple therapeutic options will emerge. PMID- 27681265 TI - Identification of interaction between HIV-1 glycoprotein 41 and integrase. AB - Human immunodeficiency virus-1 (HIV-1) encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between the HIV-1 proteins to better understand the role played by viral protein-protein interactions in the life cycle of HIV-1. Genes encoding the 15 viral proteins from the HIV-1 strain AD8 were inserted into the plasmids of a yeast two-hybrid system. By screening 120 pairs of proteins, interactions between seven pairs were found. This led to the discovery of an interaction between the HIV-1 proteins integrase (IN) and glycoprotein 41 (gp41), which was confirmed by both co-immunoprecipitation (Co IP) assays and fluorescence resonance energy transfer (FRET) imaging in live cells. In addition, it was found that the amino acids at positions 76-100 of gp41 are required for it to bind to IN. Deletion of this region from gp41 prevented its interaction with IN and reduced the production of HIV-1 in 293T cells. This study provides new information on HIV-1 protein-protein interactions which improves the understanding of the biological functions of gp41 and IN during the virus life cycle. PMID- 27681266 TI - Immunosuppressive Treatment Alters Secretion of Ileal Antimicrobial Peptides and Gut Microbiota, and Favors Subsequent Colonization by Uropathogenic Escherichia coli. AB - BACKGROUND: Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides. METHODS: Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus, or water. Feces were collected before and after treatment initiation. Ileal samples were collected after sacrifice. Fecal and ileal microbiota were analyzed by pyrosequencing of 16S rRNA genes and enumeration of selected bacteria by culture, and C-type lectins were assessed in ileal tissues by reverse transcriptase-quantitative polymerase chain reaction. RESULTS: Prednisolone disrupted fecal microbiota community structure, decreased Bacteroidetes, and increased Firmicutes in the feces. Prednisolone, tacrolimus, and mycophenolate mofetil modified fecal microbiota at the family level in each experimental replicate, but changes were not consistent between the replicates. In ileal samples, the genus Clostridium sensu stricto was dramatically reduced in the prednisolone and combined IS drug groups. These modifications corresponded to an altered ileal expression of C-type lectins Reg3gamma and Reg3beta, and of interleukin 22. Interestingly, the combined IS treatment enabled a commensal Escherichia coli to flourish, and dramatically increased colonization by uropathogenic E. coli strain 536. CONCLUSIONS: IS treatment alters innate antimicrobial defenses and disrupts the gut microbiota, which leads to overgrowth of indigenous E. coli and facilitates colonization by opportunistic pathogens. PMID- 27681269 TI - An Assessment of Urinary Biomarkers in a Series of Declined Human Kidneys Measured During Ex Vivo Normothermic Kidney Perfusion. AB - BACKGROUND: The measurement of urinary biomarkers during ex vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. METHODS: Fifty-six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based on the macroscopic appearance, renal blood flow and urine output. The scores ranged from 1 (least injury) to 5 (most severe). Levels of oxygen consumption, extraction, creatinine fall and fractional excretion of sodium were measured during perfusion. Urinary levels of NGAL, KIM-1, and ET-1 were measured after EVKP. RESULTS: Thirty-eight kidneys had an EVKP score of 1 or 2, 8 a score of 3 and 10 a score of 4 or 5. During EVKP lower levels of oxygen consumption, higher oxygen extraction, a lower decrement of serum creatinine, and higher levels of NGAL and ET-1 were associated with a higher EVKP score (P < 0.05). These parameters were also associated with a raised creatinine level in the donor before organ retrieval. Levels of KIM-1 were not associated with the perfusion parameters (P = 0.649) or renal function in the donor (R = 0.02458: P = 0.271). CONCLUSIONS: The measurement of urinary biomarkers, particularly NGAL in combination with functional perfusion parameters and the EVKP score provides an informative measure of kidney quality which may aid the decision to transplant the kidney. PMID- 27681270 TI - Cryptosporidium spp. Infection in Solid Organ Transplantation: The Nationwide "TRANSCRYPTO" Study. AB - BACKGROUND: Diarrhea is a frequent complication of solid organ transplantation. Cryptosporidiosis is classically reported in patients with acquired immunodeficiency syndrome and emerged as a cause of persistent diarrhea in solid organ transplant patients. METHODS: Through the ANOFEL Cryptosporidium National Network and the French Transplantation Society, we collected all cryptosporidiosis cases identified in solid organ transplanted patients between 2006 and 2010 in France. RESULTS: We reported 47 solid organ transplant recipients (41 kidneys) with cryptosporidiosis, mostly men (68%), with a median age of 52 (6-70) years old. Five patients had additional immunodepression favoring cryptosporidiosis (CD40 ligand deficiency [n = 1], human immunodeficiency virus infection [n = 4]). Cryptosporidiosis occurred at a median time of 3.4 (0-19.8) years posttransplant. Exposure to environmental risk factors was found before infection onset in 18 patients. Time between first symptoms and diagnosis was 10 (2-110) days. Four patients had associated extraintestinal location (biliary tract [n = 3] and lung [n = 1]). Thirty-five patients received specific therapy against cryptosporidiosis ie nitozoxanide, 25 in monotherapy, and 10 in association with azithromycin, 13 in association with immunosuppression (IS) reduction. Four patients were cured with IS treatment tapering only. The others patients had neither IS reduction nor specific therapy against cryptosporidiosis. Cryptosporidiosis was complicated by renal failure in 15 patients. Symptoms resolved after a median of 10 days of treatment. Six patients relapsed and 3 died, 1 with evolutive infection. CONCLUSIONS: Cryptosporidiosis is a late posttransplant infection that disseminated to biliar duct or lung in 9% of patients. When limited to digestive tract, infection may resolve without IS reduction. PMID- 27681272 TI - Prevalence of abnormal serum liver enzymes in patients with type 2 diabetes mellitus: a cross-sectional study from China. AB - OBJECTIVES: This cross-sectional study aimed to determine the prevalence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in Chinese type 2 diabetic patients and identify contributing risk factors. METHODS: This cross-sectional study was conducted in rural areas of China, and 1,198 type 2 diabetic patients with complete data were recruited. Elevated ALT and AST levels were defined as >40 U/L. Prevalence of abnormal liver enzymes was analyzed and multivariable analysis was used to identify independent risk factors. RESULTS: 10.3% and 6.1% diabetic patients had elevated ALT and elevated AST, respectively. The prevalence of elevated liver enzymes was gender-related; it was 13.8% in men and 7.5% in women for elevated ALT, and 7.4% in men and 3.1% in women for elevated AST. High triglyceride was positively associated with both elevated ALT (OR 1.80, 95% CI 1.08-3.01, p = 0.024) and elevated AST (OR 2.24, 95%CI 1.08-4.65, p = 0.031), while taking anti-diabetes medicine was inversely related to both elevated ALT (OR 0.48, 95% CI 0.29-0.80, p = 0.005) and elevated AST (OR 0.37, 95% CI 0.17-0.82, p = 0.014). The risk of elevated ALT in diabetic patients increased with the presence of obesity (OR 2.54, 95% CI 1.07-6.01, p = 0.034), and was lower in women (OR 0.37, 95% CI 0.19-0.72, p = 0.003). Hypertension (OR 4.33, 95% CI 1.41-13.30, p = 0.011), current drinking status (OR 2.90, 95% CI 1.21-6.96, p = 0.017) and national minority (OR 3.26, 95%CI 1.31 8.12, p = 0.011) were risk factors for elevated AST. CONCLUSION: A relatively high prevalence of abnormal serum liver enzymes in diabetic patients was demonstrated in China, especially in males. More attention should be paid to preventing liver injuries in diabetic patients. PMID- 27681271 TI - Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores. AB - PURPOSE: To describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores. MATERIALS AND METHODS: The medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization. RESULTS: Twenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic, presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR. CONCLUSION: A majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney. PMID- 27681273 TI - Renal insufficiency and left main coronary artery disease: reconsidering coronary intervention and bypass surgery. PMID- 27681274 TI - Nail Changes of Systemic Amyloidosis After Bone-Marrow Transplantation in a Patient With Multiple Myeloma. PMID- 27681276 TI - The use of transillumination as a rational approach to sclerotherapy and endovascular laser ablation of varices. Results in the use of an original instrument. AB - AIM: To explain the mode of using and the obtained results during EVLA procedures and sclerotherapies with support of Visioven(r), a laser transillumination instrument. MATERIALS AND METHODS: 205 patients suffering from Chronic Venous Insufficiency - CEAP-C stage 1-2 enrolled (103 females and 102 males) and divided into two groups. A Group: patients candidate for sclerotherapy; B Group: patients to be subjected to endovascular laser ablation (EVLA). In both groups patients were divided into two sub-groups on the basis of the use of Visioven(r) or not during the procedure. The analyzed outcome variables were the total number of cannulations necessary to treat a whole limb, and the total procedure time. RESULTS: There is a statistically significant difference between the sub-groups in which Visioven(r) was used and the ones in which the procedure has been performed without using of any tools. Both in the sclerotherapy group than in the EVLA one, there is not a statistically significant difference for the time required to complete the procedures carried out with Visioven(r) compared with the ones performed without the use of any transillumination. DISCUSSION: Complete closure of the vein was highlighted. Total number of cannulations in sclerotherapy and EVLA procedures was reduced, as a consequence of a "smart" and "targeted" treatment achieved with Visioven(r) CONCLUSION: The VISIOVEN(r) system leads to have a more rational approach to sclerotherapy or Laser Ablation of teleangectasias and reticular veins as we can immediately verify the effectiveness of the treatment and adapting it to the desired effects. KEY WORDS: Chronic Vein Insufficiency, EVLA, EVLT, Laser, Varicose vein. PMID- 27681275 TI - A methodology for assessing public health risk associated with groundwater nitrate contamination: a case study in an agricultural setting (southern Spain). AB - Groundwater nitrate contamination from agriculture is of paramount environmental interest. A continuous consumption of polluted water as drinking water or for culinary purposes is by no means a minor hazard for people's health that must be studied. This research presents a new methodology for the spatial analysis of health risk rate from intake of nitrate-polluted groundwater. The method is illustrated through its application to a water quality sampling campaign performed in the south of Spain in 2003. The probability risk model used by the US Environmental Protection Agency has been applied, considering a residential intake framework and three representative population age groups (10, 40 and 65 years).The method was based upon coupling Monte Carlo simulations and geostatistics, which allowed mapping of the health risk coefficient (RC). The maps obtained were interpreted in the framework of water resources management and user's health protection (municipalities). The results showed waterborne health risk caused by nitrate-polluted water is moderately low for the region. The observed risk was larger for the elderly and children, although no significant differences were found among the three age groups (RC average values of 95th percentile for age of 0.37, 0.33 and 0.37, respectively). Significant risk values of RC > 1 were obtained for 10 % of the surface in the NW site of the study area, where the municipalities with the highest contamination thresholds are located (agricultural activity). Nitrate concentration and intake rate stood out as the main explanatory variables of the RC. PMID- 27681279 TI - Building a sustainable future for eLife. AB - To support the long-term growth of eLife we are going to introduce a publication fee of $2500. PMID- 27681277 TI - Molecular and Biochemical Examination of Spraing Disease in Potato Tuber in Response to Tobacco rattle virus Infection. AB - Field-grown tubers of potato were examined for infection by Tobacco rattle virus (TRV) and consequent production of corky ringspot or spraing symptoms. A microarray study identified genes that are differentially expressed in tuber tissue in response to TRV infection and to spraing production, suggesting that hypersensitive response (HR) pathways are activated in spraing-symptomatic tubers. This was confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of a selected group of HR-related genes and by histochemical staining of excised tuber tissue with spraing symptoms. qRT-PCR of TRV in different regions of the same tuber slice showed that nonsymptomatic areas contained higher levels of virus relative to spraing-symptomatic areas. This suggests that spraing formation is associated with an active plant defense that reduces the level of virus in the infected tuber. Expression of two of the same plant defense genes was similarly upregulated in tubers that were infected with Potato mop-top virus, a virus that also induces spraing formation. PMID- 27681278 TI - Diffusion Tractography of the Entire Left Ventricle by Using Free-breathing Accelerated Simultaneous Multisection Imaging. AB - Purpose To develop a clinically feasible whole-heart free-breathing diffusion tensor (DT) magnetic resonance (MR) imaging approach with an imaging time of approximately 15 minutes to enable three-dimensional (3D) tractography. Materials and Methods The study was compliant with HIPAA and the institutional review board and required written consent from the participants. DT imaging was performed in seven healthy volunteers and three patients with pulmonary hypertension by using a stimulated echo sequence. Twelve contiguous short-axis sections and six four chamber sections that covered the entire left ventricle were acquired by using simultaneous multisection (SMS) excitation with a blipped-controlled aliasing in parallel imaging readout. Rate 2 and rate 3 SMS excitation was defined as two and three times accelerated in the section axis, respectively. Breath-hold and free breathing images with and without SMS acceleration were acquired. Diffusion encoding directions were acquired sequentially, spatiotemporally registered, and retrospectively selected by using an entropy-based approach. Myofiber helix angle, mean diffusivity, fractional anisotropy, and 3D tractograms were analyzed by using paired t tests and analysis of variance. Results No significant differences (P > .63) were seen between breath-hold rate 3 SMS and free-breathing rate 2 SMS excitation in transmural myofiber helix angle, mean diffusivity (mean +/- standard deviation, [0.89 +/- 0.09] * 10-3 mm2/sec vs [0.9 +/- 0.09] * 10-3 mm2/sec), or fractional anisotropy (0.43 +/- 0.05 vs 0.42 +/- 0.06). Three dimensional tractograms of the left ventricle with no SMS and rate 2 and rate 3 SMS excitation were qualitatively similar. Conclusion Free-breathing DT imaging of the entire human heart can be performed in approximately 15 minutes without section gaps by using SMS excitation with a blipped-controlled aliasing in parallel imaging readout, followed by spatiotemporal registration and entropy based retrospective image selection. This method may lead to clinical translation of whole-heart DT imaging, enabling broad application in patients with cardiac disease. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27681280 TI - Work environments for healthy and motivated public health nurses. AB - Objectives By defining health as mental health and productivity and performance as work motivation, the study aimed to identify work environments that promote the health and motivation of public health nurses, using the concept of a healthy work organizations, which encompasses the coexistence of excellent health for each worker and the productivity and performance of the organization.Methods Self administered questionnaires were sent to 363 public health nurses in 41 municipal public health departments in Chiba prefecture. The questions were comprised of the 12-item General Health Questionnaire (GHQ-12) for mental health and the Morale Measurement Scale (5 items) for work motivation. Demographic data, workplace attributes, workload, and workplace environment were set as independent variables. The Comfortable Workplace Survey (35 items in 7 areas) was used to assess workers' general work environments. The "Work Environment for Public Health Nurses" scale (25 items) was developed to assess the specific situations of public health nurses. While aggregation was carried out area by area for the general work environment, factor analysis and factor-by-factor aggregation were used for public health nurse-specific work environments. Mental health and work motivation results were divided in two based on the total scores, which were then evaluated by t-tests and chi(2) tests. Items that showed a significant correlation were analyzed using logistic regression.Results The valid responses of 215 participants were analyzed (response rate: 59.2%). For the general work environment, high scores (the higher the score, the better the situation) were obtained for "contributions to society" and "human relationships" and low scores were obtained for "career building and human resource development." For public health nurse-specific work environments, high scores were obtained for "peer support," while low scores were obtained for "easy access to advice and training" and "organizational public health initiative." Mental health was found to be related to "contributions to society" (OR=2.86), "workload" (OR=3.00), and "organizational public health initiative" (OR=2.08). Work motivation was found to be related to "contributions to society" (OR=6.73) and "recognition of public health nurse's judgment and opinion" (OR=1.59).Conclusion Both mental health and work motivation were related to working environments where public health nurses can feel that their work is meaningful to society. It is therefore necessary to improve work environments so that objectives are clearly defined to raise aspirations and nurses' activities and achievements are recognized and shared. PMID- 27681282 TI - A survey on the end-of-life care provided by medical and welfare professionals in a depopulated area. PMID- 27681281 TI - Efforts to accelerate deinstitutionalization of the public health center in a revised Law related to Mental Health and Welfare of the Persons with Mental Disorders. PMID- 27681283 TI - Awareness and health consciousness regarding the national health plan "Health Japan 21" (2nd edition) among the Japanese population in 2013 and 2014. AB - Objectives To examine the prevalence of health consciousness regarding "Health Japan 21" (2nd edition) among the Japanese population, we conducted a telephone survey of a sample extracted randomly from the whole nation in 2013 and 2014.Methods We extracted 1800 men and women with 150 persons for each gender and 10-year age group (6 age groups ranging from 20 years to 70 years and older) using Random Digital Dialing sampling. Each participant was asked about 1) recognition of the following items: "Health Japan 21," "healthy life expectancy," "metabolic syndrome (MetS)," "chronic obstructive pulmonary disease (COPD)," "locomotive syndrome," "Active Guide," "WHO Framework Convention on Tobacco Control," and "Smart Life Project" and 2) health consciousness toward the following: "health examination taken within the past one year," "smoking status," and "the amount of vegetables considered desirable to consume per day for health." We performed simple tabulation of the collected answers and cross tabulation by sex and age groups, respectively. For each question about recognition, we categorized "I know the name and meaning" and "I know the name but not the meaning" as "awareness." We compared data between 2013 and 2014, sexes, and age groups, using chi-squared test.Results In 2013, the top 5 items with high awareness were "MetS" (96.2%), "COPD" (51.1%), "healthy life expectancy" (34.2%), "locomotive syndrome" (30.2%), and "WHO Framework Convention on Tobacco Control" (28.0%). Moreover, awareness of "healthy life expectancy," "locomotive syndrome," and "Active Guide" were significantly higher in 2014 than in 2013. Meanwhile, the proportion of participants who correctly chose "350 grams" as "the desirable amount of vegetables to consume per day" was 41.6% in 2013 and became significantly higher at 50.1% in 2014. In 2013, awareness of "healthy life expectancy," "COPD," and "locomotive syndrome" and the proportion of correct answers for "the desirable amount of vegetables to consume per day" were significantly higher among women than among men. In 2013, there were significant differences among age groups in awareness of "MetS," "COPD," "healthy life expectancy," and "locomotive syndrome" and the proportion of correct answers for "the desirable amount of vegetables to consume per day."Conclusion Awareness of "healthy life expectancy," "locomotive syndrome," and health consciousness of "the desirable amount of vegetables to consume per day" were significantly higher in 2014 than in 2013. There were discrepancies on respective items among both sexes and age groups. Therefore, interventions for groups with lower awareness or health consciousness may be required. PMID- 27681285 TI - Commentary: Diagnostic devices in clinical trials have high stakes for patient care. PMID- 27681284 TI - The extent of dissociation in borderline personality disorder: A meta-analytic review. AB - Several authors have studied dissociation within the borderline personality disorder (BPD) population and postulated 3 dissociative subgroups. Conversely, other authors suggest that dissociation may play a central role in the development of trauma-related disorders and specifically in BPD. Nevertheless, the role of dissociation in BPD seems to be controversial. Our aim is to perform a meta-analytic review of the literature to evaluate the extent of dissociation in BPD compared to other psychopathological disorders to clarify its role in this specific condition. Ten eligible studies resulted in a total of 2,035 subjects. Results show that levels of dissociation are higher in BPD than in other psychiatric disorders in general, although this difference is moderate and the heterogeneity of effect sizes is large. In particular, individuals with BPD seem to show higher levels of dissociation than those with several psychiatric and personality disorders but not dissociative disorders or posttraumatic stress disorder. These findings support the fact that dissociation is not specifically a core feature of BPD and, in addition, sustain the existence of a continuum of severity within the psychiatric population. Nevertheless, the current work has several limitations related to the paucity of studies included, the heterogeneity of control groups, their clear definition, and the statistical robustness of the results. In addition, our conclusions require future research in order to explain the role of different forms of dissociation and their etiological factors among the psychiatric population. Eventually, we invite clinicians and researchers to systematically evaluate dissociation in order to reach a better diagnosis for a more specific treatment indication. PMID- 27681286 TI - Legible ledgers. PMID- 27681287 TI - A saltationist theory of cancer evolution. AB - A new study based on single-nucleus sequencing reports that triple-negative breast cancers acquire copy number aberrations in short punctuated bursts in the earliest stages of tumor evolution, rather than continuously and gradually, challenging prevailing models of tumor evolution. PMID- 27681288 TI - How the codfish changed its immune system. AB - A common ancestor of the modern codfish acquired a set of mutations that eliminated a major arm of the adaptive immune system-the MHC II pathway of antigen presentation to CD4(+) T cells. Subsequent to this event, there was a radiation of these fish in which the number and diversity of MHC I genes increased in species-specific ways. PMID- 27681289 TI - Nucleosome mapping in plasma DNA predicts cancer gene expression. AB - A new study demonstrates that genomic sequencing coverage of plasma DNA fragments around transcription start sites reflects the expression levels of genes in corresponding tumors. This approach may enable noninvasive monitoring of treatment-induced changes in gene expression for patients with cancer. PMID- 27681290 TI - Corrigendum: Parallel evolution of male germline epigenetic poising and somatic development in animals. PMID- 27681291 TI - Corrigendum: Stromal contribution to the colorectal cancer transcriptome. PMID- 27681293 TI - Erratum: Detection and interpretation of shared genetic influences on 42 human traits. PMID- 27681294 TI - Eotaxin Augments Calcification in Vascular Smooth Muscle Cells. AB - Calcification of atherosclerotic plaques in elderly patients represents a potent risk marker of cardiovascular events. Plasma analyses of patients with or without calcified plaques reveal significant differences in chemokines, particularly eotaxin, which escalates with increased calcification. We therefore, hypothesize that eotaxin in circulation augments calcification of vascular smooth muscle cells (VSMCs) possibly via oxidative stress in the vasculature. We observe that eotaxin increases the rate of calcification significantly in VSMCs as evidenced by increased alkaline phosphatase activity, calcium deposition, and osteogenic marker expression. In addition, eotaxin promotes proliferation in VSMCs and triggers oxidative stress in a NADPH oxidase dependent manner. These primary novel observations support our proposition that in the vasculature eotaxin augments mineralization. Our findings suggest that eotaxin may represent a potential therapeutic target for prevention of cardiovascular complications in the elderly. J. Cell. Biochem. 118: 647-654, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27681295 TI - Comparison of essential oils from Cistus species growing in Sardinia. AB - Cistus genus is present in Sardinia with large populations of C. monspeliensis, C. salvifolius, C. creticus subsp. eriocephalus and few stations of C. albidus, C. creticus subsp. creticus and C. creticus subsp. corsicus. No chemical studies are currently being carried on Cistus species of Sardinia. The essential oils have shown six different profiles. C. creticus subsp. eriocephalus showed a high amount of manoyl oxide and its isomer (70%). C. salvifolius has pointed out the group of labdans, (20%); another consistent percentage is made of perfumed molecules as ionone and its derivate. Several linear hydrocarbons were produced by C. monspeliensis, and the heneicosane was the most represented element. In C. albidus no labdane-type diterpenes were identified. Analysis of C. creticus subsp creticus revealed several oxygenated sesquiterpenes and labdane-type diterpenes, especially manoyl oxide. C. creticus subsp. corsicus was qualitatively very similar to C. creticus subsp. creticus, notably concerning the labdane-type compounds. PMID- 27681292 TI - Corrigendum: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. PMID- 27681296 TI - Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry. AB - Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease. PMID- 27681297 TI - Clinical outcome of endoscopic covered metal stenting for resolution of benign biliary stricture: Systematic review and meta-analysis. AB - BACKGROUND AND AIM: Management of benign biliary stricture is challenging. Endoscopic therapy has evolved as the first-line treatment for various benign biliary strictures. However, covered self-expandable metal stents (CSEMS) have not been approved by the United States Food and Drug Administration for the treatment of benign biliary stricture. With this goal, we conducted the present systemic review and meta-analysis to evaluate the efficacy and safety of endoscopic stenting with CSEMS in the treatment of benign biliary stricture. METHODS: Systematic review and meta-analysis by searching PubMed, MEDLINE and Embase databases. RESULTS: In total, 37 studies (1677 patients) fulfilled the inclusion criteria. Pooled stricture resolutions were achieved in 83% of cases. Median stent dwelling time was 4.4 months, with median endoscopic retrograde cholangiopancreatography sessions of 2.0. Stricture recurrence at 4-year follow up was 11% (95% CI, 8-14%). Pooled complication rate was 23% (95% CI, 20-26%). CONCLUSIONS: Placement of CSEMS is effective in the treatment of benign biliary stricture with relatively short stenting duration and low long-term stricture recurrence rate. However, more prospectively randomized studies are required to confirm the results. PMID- 27681299 TI - Anti-Inflammatory and Anti-Nociceptive Activities of Native and Modified Hen Egg White Lysozyme. AB - Persistent inflammatory conditions can have severe pathological consequences. Although the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is effective, it has side effects, particularly at the gastrointestinal level. There is then a high interest to identify natural anti-inflammatory compounds with no side effects. The anti-inflammatory and anti-nociceptive activities of hen egg lysozyme (LZ), both in its native form and modified by heat treatment, chemically or by enzymatic digestion have been tested in this study. The carrageenan-induced model in mice using native LZ or modified LZ has been applied. It was observed that LZ denatured by heat treatment at pH 6.0 presented 39.47% of inhibition of paw edema when administered at 30 mg/kg. LZ denatured with DL-dithiothreitol (DTT) presented a significant result of 42.10% inhibition of paw edema when administered at 30 mg/kg of animal weight. Modified LZ showed anti-inflammatory capacity comparable with the activity of the positive control dexamethasone. A classical model of acetic acid-induced abdominal writhing tests in mice was used to assess anti-nociceptive activity of native LZ and denatured heat treatment LZ and denatured chemical agent LZ. Finally, hydrolyzed native LZ presented 48% of inhibition of abdominal writhing in mice. Modified LZ with heat, chemical, and hydrolysis presented anti-inflammatory and anti-nociceptive activities independently of their natural enzymatic activity. These novel data point out the potential use of denatured and digested LZ as therapeutic agents and offer alternatives to the use of NSAIDs. LZ can be a natural source of anti inflammatory and anti-nociceptive agents. PMID- 27681300 TI - Colonization and diversification of the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) on the Canary Islands. AB - Diversification between islands and ecological radiation within islands are postulated to have occurred in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) on the Canary Islands. In this study, the biogeographical pattern of 11 species of subsect. Macaronesicae and the genetic differentiation among five species were investigated to distinguish the potential mode and mechanism of diversification and speciation. The biogeographical patterns and genetic structure were examined using statistical dispersal-vicariance analysis, Bayesian phylogenetic analysis, reduced median-joining haplotype network analysis, and discriminant analysis of principal components. The gene flow between related species was evaluated with an isolation-with-migration model. The ancestral range of the species of subsect. Macaronesicae was inferred to be Tenerife and the Cape Verde Islands, and Tenerife-La Gomera acted as sources of diversity to other islands of the Canary Islands. Inter-island colonization of E. lamarckii among the western islands and a colonization of E. regis-jubae from Gran Canaria to northern Africa were revealed. Both diversification between islands and radiation within islands have been revealed in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) of the Canary Islands. It was clear that this group began the speciation process in Tenerife-La Gomera, and this process occurred with gene flow between some related species. PMID- 27681301 TI - Selling conscience short: a response to Schuklenk and Smalling on conscientious objections by medical professionals. AB - In a thought-provoking paper, Schuklenk and Smalling argue that no right to conscientious objection should be granted to medical professionals. First, they hold that it is impossible to assess either the truth of conscience-based claims or the sincerity of the objectors. Second, even a fettered right to conscientious refusal inevitably has adverse effects on the rights of patients. We argue that the main problem with their position is that it is not derived from a broader reflection on the meaning and implications of freedom of conscience and reasonable accommodation. We point out that they collapse two related but distinct questions, that is, the subjective conception of freedom of conscience and the sincerity test. We note that they do not successfully show that the standard norm according to which exemption claims should not impose undue hardship on others is unworkable. We suggest that the main reason why arguments such as no one is forced to be a medical professional are flawed is that public norms should not constrain citizens to choose between two of their basic rights unless it is necessary. In fine, Schuklenk and Smalling, who see conscience claims as arbitrary dislikes, sell freedom of conscience short and forego any attempts at balancing the competing rights involved. We maintain the authors neglect that most of legal reasoning is contextual and that the blanket restriction of healthcare professionals' freedom of conscience is disproportionate. PMID- 27681302 TI - Reasons, reasonability and establishing conscientious objector status in medicine. AB - This paper builds upon previous work in which I argue that we should assess a provider's reasons for his or her objection before granting a conscientious exemption. For instance, if the medical professional's reasoned basis involves an empirical mistake, an accommodation is not warranted. This article poses and begins to address several deep questions about the workings of what I call a reason-giving view: What standard should we use to assess reasons? What policy should we adopt in order to evaluate the reasons offered by medical practitioners in support of their objections? I argue for a reasonability standard to perform the essential function of assessing reasons, and I offer considerations in support of a policy establishing conscientious objector status in medicine. PMID- 27681304 TI - Modeling the Transfer of Salmonella Enteritidis during Slicing of Ready-to-Eat Turkey Products Treated with Thyme Essential Oil. AB - The increased demand for low-sodium ready-to-eat (RTE) meat products highlights the need for new strategies to ensure food safety. The application of essential oils (EOs) as natural antimicrobials in the meat industry has been suggested to prevent or control cross-contamination during meat processing operations. This work aims to quantify and model the transfer of Salmonella Enteritidis during the slicing procedure of RTE turkey products treated with thyme essential oil (TEO) at a concentration of 0.1% (v/w). Two products were subjected to the slicing procedure with slicer blades inoculated with S. Enteritidis at 108 cfu/mL. The Weibull and modified Weibull predictive models were fitted to the transfer data. Twenty slices were sampled and showed positive with bacteria, indicating cross contamination. The number of cells transferred per slice decreased logarithmically during the assays. The transfer models, based on the Weibull model, were suitable to describe the bacterial transfer trend on slices in most cases. TEO treatment reduced the transfer of Salmonella on a preservative free RTE turkey product. The predictive models obtained in this study can help food quality staff and managers on the design and assessment of processes to guard RTE turkey products against Salmonella. This work supports the addition of EOs to reduce microbial risk in RTE meat products. PMID- 27681303 TI - Dental caries and risk indicators for patients with leprosy in China. AB - BACKGROUND: In leprosy, oral health is often neglected and poorly understood. This study aimed to evaluate the prevalence and risk indicators of dental caries in patients with leprosy in China. METHODS: This cross-sectional, multicentre study included 613 patients with leprosy and 602 control subjects. Based on the established standards of the World Health Organization, we investigated dental caries in cluster samplings from six so-called 'leprosy villages' in three Chinese provinces. Clinical oral examinations were performed and data were reported as decayed (D), missing (M) and filled (F) teeth (DMFT scores). RESULTS: The average DMFT scores were 10.39 in patients with leprosy (D = 4.43; M = 5.94; and F = 0.02) and 4.39 in control individuals (D = 2.29; M = 2.02; F = 0.08). The DMFT scores were statistically significantly different in patients with different ages, educational backgrounds and daily brushing frequency (P < 0.05). High DMFT scores were related to age, low educational levels and poor toothbrushing habits. CONCLUSIONS: The results indicate that patients with leprosy have a high prevalence of severe dental caries. Effective therapy and oral health education should be enhanced for this group of patients. PMID- 27681305 TI - BRAF-V600E expression correlates with ameloblastoma aggressiveness. AB - AIMS: The aim of this study was to investigate whether the expression of BRAF V600E determines an aggressive clinical and molecular presentation of ameloblastoma. METHODS AND RESULTS: Ninety-three cases of solid ameloblastomas were arranged in a 1.0-mm tissue microarray (TMA) block. Immunohistochemistry against a large panel of cytokeratins (CK), epidermal growth factor receptor (EGFR), parathyroid hormone-related peptide (PTHrP), syndecan-1, Ki67, p53 and BRAF-V600E were performed. Clinicopathological parameters, including sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic pattern, vestibular/lingual and basal cortical plates disruption and follow-up data, were obtained from patients' medical records. Immunoexpression of BRAF-V600E was investigated in 73 cases that remained available in TMA sections. Our results indicated that 46.6% (34 cases) demonstrated cytoplasm positivity (six weak and 28 strong positivity). BRAF-V600E expression was associated significantly with the expression of CK8 (P = 0.00077), CK16 (P = 0.05), PTHrP (P = 0.0082) and p53 (P = 0.0087). Additionally, a significant association was seen with the presence of recurrences (P = 0.0008), multilocular radiographic appearance (P = 0.044) and disruption of basal bone cortical (P = 0.05). Univariate analysis showed that BRAF-positive cases (P = 0.001), EGFR negative/weak positive cases (P = 0.03) and multilocular tumours (P = 0.04) had a significantly lower disease-free survival rate, but these parameters were not considered independent prognostic factors in the multivariate analysis (P > 0.05). CONCLUSIONS: Our findings suggest an association of BRAF-V600E with parameters of a more aggressive behaviour of ameloblastoma, supporting the future use of BRAF inhibitors for targeted therapy of this neoplasm. PMID- 27681306 TI - Recording duration and short-term reproducibility of heart rate and QT interval variability in patients with myocardial infarction. AB - Beat-to-beat variability of the QT interval (QTV) measured on surface ECG has emerged as a potential marker for ventricular repolarization instability and has been used along with heart rate variability (HRV) to predict arrhythmic risk. Since measurement modalities of QTV have not been standardized, the objective of this study was to investigate the effect of ECG recording duration on QTV as well as HRV. Using a database of 30 min ECG recorded from 500 patients with acute myocardial infraction during rest, we extracted RR and QT interval time series and estimated different HRV and QTV metrics over windows of varying length. Analysis of variance (ANOVA) and intra-class correlation analyses were computed to investigate the effect of recording length on consistency and short-term reproducibility of HRV and QTV variables. Good consistency (non-significant ANOVA results) and short-term reproducibility (intra-class correlation coefficients >0.8) were demonstrated for all but standard deviation based metrics when at least 200 beats were included in the estimation. In conclusion, QTV can be quantified from resting ECG with good short-term consistency and reproducibility that is comparable to that of HRV. PMID- 27681308 TI - A Case of Acquired Gilbert's Syndrome. PMID- 27681309 TI - Personal Finance for Pediatric Trainees. PMID- 27681307 TI - Uniparental disomy causes deficiencies of vitamin K-dependent proteins. AB - : Essentials Vitamin K-dependent coagulant factor deficiency (VKCFD) is a rare autosomal recessive disorder. We describe a case of inherited VKCFD due to uniparental disomy. The homozygous mutation caused the absence of GGCX isoform 1 and overexpression of Delta2GGCX. Hepatic and non-hepatic vitamin K-dependent proteins must be assayed to monitor VKCFD treatment. SUMMARY: Background Inherited deficiency of all vitamin K-dependent coagulant factors (VKCFD) is a rare autosomal recessive disorder caused by mutations in the gamma-glutamyl carboxylase gene (GGCX) or the vitamin K epoxide reductase gene (VKORC1), with great heterogeneity in terms of both clinical presentation and response to treatment. Objective To characterize the molecular basis of VKCFD in a Spanish family. Methods and Results Sequencing of candidate genes, comparative genomic hybridization and massive sequencing identified a new mechanism causing VKCFD in the proband. Uniparental disomy (UPD) of chromosome 2 caused homozygosity of a mutation (c.44-1G>A) resulting in aberrant GGCX splicing. This change contributed to absent expression of the mRNA coding for the full-length protein, and to four fold overexpression of the smaller mRNA isoform lacking exon 2 (Delta2GGCX). Delta2GGCX might be responsible for two unexpected clinical observations in the patient: (i) increased plasma osteocalcin levels following vitamin K1 supplementation; and (ii) a mild non-bleeding phenotype. Conclusions Our study identifies a new autosomal disease, VKCFD1, caused by UPD. These data suggest that the Delta2GGCX isoform may retain enzymatic activity, and strongly encourage the evaluation of both hepatic and non-hepatic vitamin K-dependent proteins to assess differing responses to vitamin K supplementation in VKCFD patients. PMID- 27681310 TI - Pediatric-Informed Facilitation of Patient-Centered Medical Home Transformation. AB - Patient-centered medical home (PCMH) transformation has been challenging for pediatric practices, in part because of the National Committee for Quality Assurance (NCQA) PCMH focus on conditions and processes specific to adult patients. Realizing the potential challenges faced by pediatric practices, Vermont supported pediatric-informed facilitators to help practices during PCMH transformation. This study characterizes the impact of pediatric-informed facilitators; provides benchmark data on NCQA scores, number of facilitation meetings, and the time between facilitation start and end; and compares pediatric and adult-serving practices. We found no difference between pediatric and matched adult-serving practices in NCQA score, number of facilitation meetings, or weeks to NCQA scoring. These results suggest that pediatric-informed facilitators can help pediatric practices achieve NCQA PCMH recognition on par with practices serving adult patients. Supporting primary care practices with specialty-informed facilitators can assist integration into health care reform efforts. PMID- 27681311 TI - Short-term treatment of equine wounds with orf virus IL-10 and VEGF-E dampens inflammation and promotes repair processes without accelerating closure. AB - Healing is delayed in limb wounds relative to body wounds of horses, partly because of sustained inflammation and inefficient angiogenesis. In laboratory animals, proteins derived from orf virus modulate these processes and enhance healing. We aimed to compare immune cell trafficking and the inflammatory, vascular, and epidermal responses in body and limb wounds of horses and then to investigate the impact of orf virus interleukin-10 and vascular endothelial growth factor-E on these processes. Standardized excisional wounds were created on the body and forelimb of horses and their progression monitored macroscopically until healed. Tissue samples were harvested to measure the expression of genes regulating inflammation and repair (quantitative polymerase chain reaction) and to observe epithelialization (histology), innate immune cell infiltration, and angiogenesis (immunofluorescence). Delayed healing of limb wounds was characterized by intensified and extended pro-inflammatory signaling and exacerbated innate immune response, concomitant with the absence of anti inflammatory eIL-10. Blood vessels were initially more permeable and then matured belatedly, concomitant with retarded production of angiogenic factors. Epithelial coverage was achieved belatedly in limb wounds. Viral proteins were administered to wounds of one body and one limb site/horse at days 1-3, while wounds at matching sites served as controls. Treatment dampened pro-inflammatory gene expression and the innate immune response in all wounds. It also improved angiogenic gene expression, but primarily in body wounds, where it altered blood vessel density and myofibroblast persistence. Moreover, the viral proteins increased epithelialization of all wounds. The short-term viral protein therapy did not, however, improve the healing rate of wounds in either location, likely due to suboptimal dosing. In conclusion, we have further detailed the processes contributing to protracted healing in limb wounds of horses and shown that short term administration of viral proteins exerts several promising though transient effects that, if optimized, may positively influence healing. PMID- 27681314 TI - A spouse's perspective on life with aphasia. AB - The author describes the effect of her husband's stroke and aphasia on her life. She writes of the myriad adjustments that are made in everyday life, developing coping skills, seeking out information and educating herself about aphasia, and establishing support networks, among other responses. PMID- 27681313 TI - Formation of droplet interface bilayers in a Teflon tube. AB - Droplet-interface bilayers (DIBs) have applications in disciplines ranging from biology to computing. We present a method for forming them manually using a Teflon tube attached to a syringe pump; this method is simple enough it should be accessible to those without expertise in microfluidics. It exploits the properties of interfaces between three immiscible liquids, and uses fluid flow through the tube to pack together drops coated with lipid monolayers to create bilayers at points of contact. It is used to create functional nanopores in DIBs composed of phosphocholine using the protein alpha-hemolysin (alphaHL), to demonstrate osmotically-driven mass transfer of fluid across surfactant-based DIBs, and to create arrays of DIBs. The approach is scalable, and thousands of DIBs can be prepared using a robot in one hour; therefore, it is feasible to use it for high throughput applications. PMID- 27681315 TI - The impact of aphasia on the patient and family in the first year poststroke. AB - This article reports a study that addressed coping strategies and possible related factors in 58 patients with aphasia and their relatives in the first year poststroke. Coping strategies, psychosocial changes, expectations of psychosocial adjustment, illness-related causal attributions, control beliefs, and activities of daily living were investigated in a longitudinal study. The data show that subjects with aphasia and their relatives experience significantly more severe professional and social changes than do subjects without aphasia and their families. Aphasia, however, seems to have no substantial effect on coping strategies, expectancies of adjustment, causal and control attributions, or activities of daily living as measured by the Barthel Index. PMID- 27681316 TI - Adaptation to stroke: Comparison of spouses of stroke survivors with and without aphasia. AB - The purpose of this study was to compare adaptation to a partner's stroke in spouses of aphasic stroke survivors (SASS) and spouses of nonaphasic stroke survivors (SNASS) over time. Cognitive appraisal of the impact of stroke, difficult adaptive tasks, and depression were examined in 15 SASS and 20 SNASS. Data were collected prior to discharge from rehabilitation and at 6 to 10 weeks and 1 year postdischarge. For the entire group, depression scores decreased significantly (p < .05) over time. The reduction in depression was equivalent in both groups. Differences and similarities in patterns of change in appraisal of stroke and in adaptive tasks are discussed. PMID- 27681312 TI - FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase. AB - Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KODAT) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis. Moreover, FoxO1 KODAT mice exhibit an increased sucrose preference in concomitance with higher dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamine synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that FoxO1 in DA neurons is an important transcriptional factor that directs the coordinated control of energy balance, thermogenesis and glucose homoeostasis. PMID- 27681317 TI - Family perspectives from three aphasia centers in Ontario, Canada. AB - Speech-language pathologists and social workers at the three Aphasia Centres in Ontario, Canada, work in partnership with aphasic adults and their families to increase communicative access to participation in various aspects of social and community life. The delivery of optimal service in this context requires an expansion of the traditional role played by speech-language pathologists in the field of aphasia. Illustrative ideas, activities, and programs developed by the three centers are described with emphasis on the benefits of a professional partnership between the professions of speech-language pathology and social work. PMID- 27681318 TI - Alternative family education programming for adults with chronic aphasia. AB - Serious psychological consequences and limited social access are significant effects of chronic aphasia due to stroke. There appears to be a need for ongoing family education and counseling throughout the chronic stage in order to address the psychosocial needs of these individuals and their families. We describe an alternative approach to family education for chronically aphasic individuals. Six month follow-up results suggest that this educational program has a positive impact on social behaviors, understanding of aphasia, and family communication patterns. The importance of developing and providing educational programs to the chronically impaired beyond the point of formal rehabilitation is discussed. PMID- 27681319 TI - Who's the "expert"? Amateur and professional judgment of aphasic communication. AB - Partners of aphasie individuals knew them before they suffered a stroke and have ample opportunity to observe their everyday functional communication. Therefore, at first glance, partners seem to be potentially valid judges of disability assessment. However, the literature depicts the partner mainly as a person in need of support. Twenty-eight partners were asked to rate the verbal communicative abilities of aphasie individuals. The results clearly establish partners as accurate judges of verbal communicative disabilities. It is argued that assessment of a partner's knowledge about aphasie disabilities should be assessed by means of concise, condition-specific tools. PMID- 27681320 TI - Report of a questionnaire survey of poststroke patients with aphasia and their families. AB - In a study made by The Stroke and Aphasia Federation Finland, a little less than a quarter of the aphasic patients and their families could not cope with the change in their life caused by stroke. Patients' and families' functionality decreased, and their social contacts either decreased or ended. These were the factors that prevented families from adapting to new situations. Patients and famiIies felt that they had received too little information about the illness and various benefits available. Families also needed more mental support. Those who lived in big cities or in the scattered areas felt that the rehabilitation was also insufficient. PMID- 27681321 TI - Ethical issues for persons with aphasia and their families. AB - Ethical issues frequently arise in the care of patients with aphasia and their families. The family is often the most important group with whom an individual interacts and with whom crucial life decisions are made following brain injury. For individuals with aphasia, who may have trouble understanding information and communicating their wishes, the patient's role and thefamily's rolewith decision making may be particularly complex. This article discusses (a) patient self determination, (b) evaluation ofthe patient's decision-making capacity, PMID- 27681322 TI - A commentary on "Ethical Issues for Persons with Aphasia and Their Families". PMID- 27681323 TI - From the editor. PMID- 27681324 TI - Foreword. PMID- 27681325 TI - Lu-, Sm-, and Gd-Doped Ceria: A Comparative Approach to Their Structural Properties. AB - A room temperature structural study has been performed through the whole compositional range of the (Ce1-xLux)O2-x/2 system by synchrotron X-ray diffraction and MU-Raman spectroscopy. Samples were synthesized by thermal treatment in air at 1373 K of coprecipitated mixed oxalates. A CeO2-based solid solution with a fluorite-type structure (F) was found to be stable up to x = 0.4, while at higher Lu content a (F + C) biphasic region was observed, with C being the cubic atomic arrangement typical of sesquioxides of the heaviest rare earths. A comparative approach including also results deriving from other (Ce1-xREx)O2 x/2 systems (RE = Gd and Sm) allowed us to conclude that the compositional extent of the F solid solution is a complex function of RE3+ size and RE compressibility. On this basis, the dependence of ionic conductivity on the RE identity was interpreted as related both to the Ce4+/RE3+ size closeness and to RE compressibility. Ce4+/RE3+ dimensional issues were also revealed to rule the appearance of the hybrid structure observed in the two aforementioned systems, consisting of the intimate intergrowth of C microdomains within the F-based host lattice. Moreover, a more extended definition of F-based solid solution, including also the hybrid structure, is formulated; the latter is meant as a modification of the former, occurring when mainly RE-vacancy aggregates are incorporated into the host lattice in spite of isolated RE ions. By MU-Raman spectroscopy it was possible to demonstrate that the mechanism of oxygen vacancy formation is common to all the systems studied, provided that the structure of the F-based solid solution, also including the hybrid structure, is retained. PMID- 27681326 TI - Genetic and Biochemical Biomarkers in Canine Glaucoma. AB - In many health-related fields, there is great interest in the identification of biomarkers that distinguish diseased from healthy individuals. In addition to identifying the diseased state, biomarkers have potential use in predicting disease risk, monitoring disease progression, evaluating treatment efficacy, and informing pathogenesis. This review details the genetic and biochemical markers associated with canine primary glaucoma. While there are numerous molecular markers (biochemical and genetic) associated with glaucoma in dogs, there is no ideal biomarker that allows early diagnosis and/or identification of disease progression. Genetic mutations associated with canine glaucoma include those affecting ADAMTS10, ADAMTS17, Myocilin, Nebulin, COL1A2, RAB22A, and SRBD1. With the exception of Myocilin, there is very limited crossover in genetic biomarkers identified between human and canine glaucomas. Mutations associated with canine glaucoma vary between and within canine breeds, and gene discoveries therefore have limited overall effects as a screening tool in the general canine population. Biochemical markers of glaucoma include indicators of inflammation, oxidative stress, serum autoantibodies, matrix metalloproteinases, tumor necrosis factor-alpha, and transforming growth factor-beta. These markers include those that indicate an adaptive or protective response, as well as those that reflect the damage arising from oxidative stress. PMID- 27681327 TI - Climate Change Influences Potential Distribution of Infected Aedes aegypti Co Occurrence with Dengue Epidemics Risk Areas in Tanzania. AB - BACKGROUND: Dengue is the second most important vector-borne disease of humans globally after malaria. Incidence of dengue infections has dramatically increased recently, potentially due to changing climate. Climate projections models predict increases in average annual temperature, precipitation and extreme events in the future. The objective of this study was to assess the effect of changing climate on distribution of dengue vectors in relation to epidemic risk areas in Tanzania. METHODS/FINDINGS: We used ecological niche models that incorporated presence-only infected Aedes aegypti data co-occurrence with dengue virus to estimate potential distribution of epidemic risk areas. Model input data on infected Ae. aegypti was collected during the May to June 2014 epidemic in Dar es Salaam. Bioclimatic predictors for current and future projections were also used as model inputs. Model predictions indicated that habitat suitability for infected Ae. aegypti co occurrence with dengue virus in current scenarios is highly localized in the coastal areas, including Dar es Salaam, Pwani, Morogoro, Tanga and Zanzibar. Models indicate that areas of Kigoma, Ruvuma, Lindi, and those around Lake Victoria are also at risk. Projecting to 2020, we show that risk emerges in Mara, Arusha, Kagera and Manyara regions, but disappears in parts of Morogoro, Ruvuma and near Lake Nyasa. In 2050 climate scenario, the predicted habitat suitability of infected Ae. aegypti co-occurrence with dengue shifted towards the central and north-eastern parts with intensification in areas around all major lakes. Generally, model findings indicated that the coastal regions would remain at high risk for dengue epidemic through 2050. CONCLUSION/SIGNIFICANCE: Models incorporating climate change scenarios to predict emerging risk areas for dengue epidemics in Tanzania show that the anticipated risk is immense and results help guiding public health policy decisions on surveillance and control of dengue epidemics. A collaborative approach is recommended to develop and adapt control and prevention strategies. PMID- 27681329 TI - Band-Selective 2D HSQMBC: A Universal Technique for Detection and Measurement of 35,37Cl Isotope Effects for 13C Nuclei. AB - A novel technique that allows efficient measurement of the 35,37Cl isotope pattern for any 13C resonance has been developed. The band-selective CLIP-HSQMBC experiment is reliable and universally applicable for the indirect measurement of the 35,37Cl isotope shift of 13C resonances. The experiment provides advantages over conventional 1D 13C NMR and the recently developed bs-HSQC experiments. The utility and performance of the bs-CLIP-HSQMBC experiment is demonstrated for polyhalogenated synthons in a synthetic route and for a polyhalogenated marine natural product. PMID- 27681330 TI - Number of Lymph Nodes in Primary Nodal Basin and a "Second Look" Protocol as Quality Indicators for Optimal Nodal Staging of Colon Cancer. AB - CONTEXT: -Evaluation of 12 or more lymph nodes (LNs) is currently used as a quality indicator for adequacy of pathologic examination of colon cancer resections. OBJECTIVE: -To evaluate the utility of a focused LN search in the immediate vicinity of the tumor and a "second look" protocol in improving LN staging in colon cancer. DESIGN: -Lymph nodes were submitted separately from the primary nodal basin (PNB) and secondary nodal basin (SNB) defined as an area less than 5 cm away and an area greater than 5 cm away from the tumor edge, respectively, in 201 consecutive resections (2010-2013). One hundred sixty-eight consecutive tumors (2006-2009) were used as a control group. A second search was performed in all cases that were N0 after the first search. RESULTS: -In cases that were N0 after the first search, 20.9 +/- 10.8 LNs were collected from the PNB, compared to 8.5 +/- 9.1 from the SNB. Positive LNs were found in N+ tumors in the PNB in all cases but in only 9% (4 of 46) of SNBs (P < .001). A second search increased node count by an average of 10 additional LNs. In 5 of 114 cases (4.4%), N0 after the first search converted to N+ after a second search that yielded 1 to 4 positive LNs, all of which were in the PNB. CONCLUSIONS: -Emphasis on the number of LNs examined from the PNB and a "second look" protocol improve nodal staging. PMID- 27681328 TI - Angiotensin-(1-7) protects from brain damage induced by shiga toxin 2-producing enterohemorrhagic Escherichia coli. AB - Shiga toxin 2 (Stx2)-producing enterohemorrhagic induced brain damage. Since a cerebroprotective action was reported for angiotensin (Ang)-(1-7), our aim was to investigate whether Ang-(1-7) protects from brain damage induced by Stx2 producing enterohemorrhagic Escherichia coli The anterior hypothalamic area of adult male Wistar rats was injected with saline solution or Stx2 or Stx2 plus Ang (1-7) or Stx2 plus Ang-(1-7) plus A779. Rats received a single injection of Stx2 at the beginning of the experiment, and Ang-(1-7), A779, or saline was administered daily in a single injection for 8 days. Cellular ultrastructural changes were analyzed by transmission electron microscopy. Stx2 induced neurodegeneration, axonal demyelination, alterations in synapse, and oligodendrocyte and astrocyte damage, accompanied by edema. Ang-(1-7) prevented neuronal damage triggered by the toxin in 55.6 +/- 9.5% of the neurons and the Stx2-induced synapse dysfunction was reversed. In addition, Ang-(1-7) blocked Stx2-induced demyelination in 92 +/- 4% of the axons. Oligodendrocyte damage caused by Stx2 was prevented by Ang-(1-7) but astrocytes were only partially protected by the peptide (38 +/- 5% of astrocytes were preserved). Ang-(1-7) treatment resulted in 50% reduction in the number of activated microglial cells induced by Stx2, suggesting an anti-inflammatory action. All these beneficial effects elicited by Ang-(1-7) were blocked by the Mas receptor antagonist and thus it was concluded that Ang-(1-7) protects mainly neurons and oligodendrocytes, and partially astrocytes, in the central nervous system through Mas receptor stimulation. PMID- 27681331 TI - The Spectrum of Histologic Findings in Hepatic Outflow Obstruction. AB - CONTEXT: -Cardiac hepatopathy and Budd-Chiari syndrome are 2 forms of hepatic venous outflow obstruction with different pathophysiology but overlapping histologic findings, including sinusoidal dilation and centrilobular necrosis. OBJECTIVE: -To determine whether a constellation of morphologic findings could help distinguish between the 2 and could suggest the diagnoses in previously undiagnosed patients. DESIGN: -We identified 26 specimens with a diagnosis of cardiac hepatopathy and 23 with a diagnosis of Budd-Chiari syndrome. Slides stained with hematoxylin and eosin and with trichrome were evaluated for several distinctive histologic findings. RESULTS: -Features common to both forms of hepatic outflow obstruction included sinusoidal dilation and portal tract changes of fibrosis, chronic inflammation, and bile ductular reaction. Histologic findings significantly more common in cardiac hepatopathy included pericellular/sinusoidal fibrosis and fibrosis around the central vein. Only centrilobular hepatocyte dropout/necrosis was significantly more common in Budd Chiari, regardless of duration. CONCLUSIONS: -The finding of pericellular/sinusoidal fibrosis in cardiac hepatopathy compared with Budd-Chiari is not unexpected, given the chronic nature of most cardiac hepatopathy. Portal tract changes are common in both forms of hepatic outflow obstruction and should not deter one from making the diagnosis of hepatic outflow obstruction. Fibrosis along sinusoids and around the central vein may be suggestive of cardiac hepatopathy in biopsies from patients without a prior diagnosis. PMID- 27681332 TI - Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma. PMID- 27681333 TI - Impact of Uniform Methods on Interlaboratory Antibody Titration Variability: Antibody Titration and Uniform Methods. AB - CONTEXT: -Substantial variability between different antibody titration methods prompted development and introduction of uniform methods in 2008. OBJECTIVE: -To determine whether uniform methods consistently decrease interlaboratory variation in proficiency testing. DESIGN: -Proficiency testing data for antibody titration between 2009 and 2013 were obtained from the College of American Pathologists. Each laboratory was supplied plasma and red cells to determine anti-A and anti-D antibody titers by their standard method: gel or tube by uniform or other methods at different testing phases (immediate spin and/or room temperature [anti-A], and/or anti-human globulin [AHG: anti-A and anti-D]) with different additives. Interlaboratory variations were compared by analyzing the distribution of titer results by method and phase. RESULTS: -A median of 574 and 1100 responses were reported for anti-A and anti-D antibody titers, respectively, during a 5-year period. The 3 most frequent (median) methods performed for anti-A antibody were uniform tube room temperature (147.5; range, 119-159), uniform tube AHG (143.5; range, 134-150), and other tube AHG (97; range, 82-116); for anti-D antibody, the methods were other tube (451; range, 431-465), uniform tube (404; range, 382 462), and uniform gel (137; range, 121-153). Of the larger reported methods, uniform gel AHG phase for anti-A and anti-D antibodies had the most participants with the same result (mode). For anti-A antibody, 0 of 8 (uniform versus other tube room temperature) and 1 of 8 (uniform versus other tube AHG), and for anti-D antibody, 0 of 8 (uniform versus other tube) and 0 of 8 (uniform versus other gel) proficiency tests showed significant titer variability reduction. CONCLUSION: -Uniform methods harmonize laboratory techniques but rarely reduce interlaboratory titer variance in comparison with other methods. PMID- 27681334 TI - Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia. AB - CONTEXT: -The placenta is an important component in understanding the fetal response to intrauterine Zika virus infection, but the pathologic changes in this organ remain largely unknown. Hofbauer cells are fetal-derived macrophages normally present in the chorionic villous stroma. They have been implicated in a variety of physiological and pathologic processes, in particular involving infectious agents. OBJECTIVES: -To characterize the fetal and maternal responses and viral localization in the placenta following Zika virus transmission to an 11 weeks' gestation fetus. The clinical course was notable for prolonged viremia in the mother and extensive neuronal necrosis in the fetus. The fetus was delivered at 21 weeks' gestation after pregnancy termination. DESIGN: -The placenta was evaluated by using immunohistochemistry for inflammatory cells (macrophages/monocytes [Hofbauer cells], B and T lymphocytes) and proliferating cells, and an RNA probe to Zika virus. The fetal brain and the placenta were previously found to be positive for Zika virus RNA by reverse transcription polymerase chain reaction. RESULTS: -The placenta demonstrated prominently enlarged, hydropic chorionic villi with hyperplasia and focal proliferation of Hofbauer cells. The degree of Hofbauer cell hyperplasia gave an exaggerated immature appearance to the villi. No acute or chronic villitis, villous necrosis, remote necroinflammatory abnormalities, chorioamnionitis, funisitis, or hemorrhages were present. An RNA probe to Zika virus was positive in villous stromal cells, presumably Hofbauer cells. CONCLUSIONS: -Zika virus placental infection induces proliferation and prominent hyperplasia of Hofbauer cells in the chorionic villi but does not elicit villous necrosis or a maternal or fetal lymphoplasmacellular or acute inflammatory cell reaction. PMID- 27681335 TI - Attitudes and Beliefs of Pathology Residents Regarding the Subspecialty of Clinical Chemistry: Results of a Survey. AB - CONTEXT: -Previous studies suggest that training in pathology residency programs does not adequately prepare pathology residents to become competent in clinical chemistry. OBJECTIVES: -To define the beliefs of pathology residents in the United States regarding their preparation for practicing clinical chemistry in their career, their attitude toward the discipline, and the attractiveness of clinical chemistry as a career. DESIGN: -The residents of all pathology residency programs in the United States were given the opportunity to participate in an online survey. RESULTS: -Three hundred thirty-six pathology residents responded to the survey. Analysis of the survey results indicates that pathology residents are more likely to believe that their income may be lower if they select a career that has a clinical chemistry focus and that their faculty do not value clinical chemistry as much as the anatomic pathology part of the residency. Residents also report that clinical chemistry is not as enjoyable as anatomic pathology rotations during residency or preferable as a sole career path. A large proportion of residents also believe that they will be slightly prepared or not prepared to practice clinical chemistry by the end of their residency and that they do not have enough background and/or time to learn clinical chemistry during their residency programs to be able to practice this specialty effectively post graduation. CONCLUSIONS: -Our survey results suggest that many pathology residents do not have a positive attitude toward clinical chemistry and do not experience a supportive learning environment with an expectation that they will become competent in clinical chemistry with a residency alone. PMID- 27681337 TI - A not-so-sweet diagnosis - leukocytoclastic vasculitis masquerading as squamous cell carcinoma. AB - Leukocytoclastic vasculitis (LCV) is a rare small-vessel vasculitis characterised by neutrophilic inflammation of post-capillary venules. Incidence varies from 3 to 4.5 per 100 000 people per year. Patients typically present with painful, itchy purpura and erythema, although clinical manifestations can vary making diagnosis a challenge. We report the case of a 75-year-old man with a history of a previously completely excised and grafted squamous cell carcinoma (SCC) on the dorsum of his hand, who presented with an acutely swollen, erythematous and ulcerated lesion adjacent to the graft site. A shave biopsy failed to definitively exclude SCC recurrence. He was referred to the Plastics team who initially suspected Sweet's syndrome but could not rule out SCC recurrence. The patient underwent formal mapping incisional biopsies that later diagnosed LCV. He was managed conservatively and made an excellent recovery. We present clinical photographs and histology to illustrate disease progression. LCV is typically self-limiting with a good overall prognosis, but a minority of patients follow a protracted course, which may require treatment in the form of systemic corticosteroids or colchicine. LCV can only be confirmed histologically. We present this case in order to highlight the importance of adequate tissue biopsy when there is diagnostic uncertainty with an acute dermatosis, particularly in the context of previous skin malignancy. PMID- 27681336 TI - TRPM7-like channels are functionally expressed in oocytes and modulate post fertilization embryo development in mouse. AB - The Transient Receptor Potential (TRP) channels are a family of cationic ion channels widely distributed in mammalian tissues. In general, the global genetic disruption of individual TRP channels result in phenotypes associated with impairment of a particular tissue and/or organ function. An exception is the genetic ablation of the TRP channel TRPM7, which results in early embryonic lethality. Nevertheless, the function of TRPM7 in oocytes, eggs and pre implantation embryos remains unknown. Here, we described an outward rectifying non-selective current mediated by a TRP ion channel in immature oocytes (germinal vesicle stage), matured oocytes (metaphase II eggs) and 2-cell stage embryos. The current is activated by specific agonists and inhibited by distinct blockers consistent with the functional expression of TRPM7 channels. We demonstrated that the TRPM7-like channels are homo-tetramers and their activation mediates calcium influx in oocytes and eggs, which is fundamental to support fertilization and egg activation. Lastly, we showed that pharmacological inhibition of the channel function delays pre-implantation embryo development and reduces progression to the blastocyst stage. Our data demonstrate functional expression of TRPM7-like channels in mouse oocytes, eggs and embryos that may play an essential role in the initiation of embryo development. PMID- 27681338 TI - Reasons for family involvement in elective surgical decision-making in Taiwan: a qualitative study. AB - AIMS AND OBJECTIVES: To inquire into the reasons for family involvement in adult patients' surgical decision-making processes from the point of view of the patients' family. BACKGROUND: Making a patient the centre of medical decision making is essential for respecting individual's autonomy. However, in a Chinese society, family members are often deeply involved in a patient's medical decision making. Although family involvement has long been viewed as an aspect of the Chinese culture, empirical evidence of the reasons for family involvement in medical decision-making has been lacking. DESIGN: A qualitative study. METHOD: In order to record and examine reasons for family involvement in adult patients' surgical decision-making, 12 different family members of 12 elective surgery patients were interviewed for collecting and analysing data. RESULTS: Three major reasons for family involvement emerged from the data analyses: (1) to share responsibility; (2) to ensure the correctness of medical information; and (3) to safeguard the patient's well-being. These findings also reveal that culture is not the only reason for family involvement. CONCLUSIONS: Making decision to undergo a surgery is a tough and stressful process for a patient. Family may provide the patient with timely psychological support to assist the patient to communicate with his or her physician(s) and other medical personnel to ensure their rights. It is also found that due to the imbalanced doctor-patient power relationship, a patient may be unable, unwilling to, or even dare not, tell the whole truth about his or her illness or feelings to the medical personnel. Thus, a patient would expect his or her family to undertake such a mission during the informed consent and decision-making processes. RELEVANCE TO CLINICAL PRACTICE: The results of this study may provide medical professionals with relevant insights into family involvement in adult patients' surgical decision-making. PMID- 27681339 TI - Illicit Drugs in Oral Fluid: Evaluation of Two Collection Devices. AB - Driving after illicit drug use is a worldwide growing concern requiring rapid and sensitive screening at the roadside. It is noteworthy that the sampling method used to collect oral fluid (OF) may significantly influence drug concentrations in the collected sample and thus alter the accuracy of the measurement. We evaluated two OF collection devices, Quantisal(r) and Certus(r) collectors, for their suitability for collecting samples to allow laboratory confirmation of driving after illicit drug use. Four parameters were studied including (i) the collected OF volume; (ii) the recovery efficiency using OFs spiked with opiates, cannabinoids, amphetamines, cocaine and its metabolites; (iii) drug stability after storage for 1, 7 and 14 days at -20 degrees C, +4 degrees C and room temperature; and (iv) the impact of mouth cells present in the collected OF on drug stability. Drug concentrations were measured using gas and liquid chromatography-mass spectrometry. Certus(r) collector allowed the collection of significantly larger (0.94 +/- 0.18 mL vs. 0.84 +/- 0.06 mL, P = 0.08) but less reproducible OF volumes (19 vs. 6.7%) compared with Quantisal(r) collector. Drug recovery was significantly better with Quantisal(r) than with Certus(r) collector, especially when used to detect cannabinoids (0.94 vs. 0.54, P < 0.001 for ?9-tetrahydrocannabinol (THC)). For both OF collectors, storage at 4 degrees C was preferable except for methadone, the stability of which was altered by adherence to the collector device. In the presence of mouth cells in the OF sample, THC concentrations were significantly decreased at Day 7 in comparison with Day 1 with both collection devices (P = 0.001 with Quantisal(r) collector and P = 0.01 with Certus(r) collector). In conclusion, Quantisal(r) collector is more reliable than Certus(r) collector although the practicability of both devices remains to be determined at the roadside. PMID- 27681340 TI - Determination of Drugs of Abuse in a Single Sample of Human Teeth by a Gas Chromatography-Mass Spectrometry Method. AB - The purpose of this study was to develop and validate a gas chromatography-mass spectrometry method to detect drugs of abuse in a single sample of tooth. Pulverized samples of dental materials were subjected to acid hydrolysis to detect opiates, cocaine and their metabolites. The residual dental materials from these analyses were subjected to basic extraction to detect cannabis products (Delta9-tetrahydrocannabinol, cannabidiol and cannabinol). The method showed a good linearity between 0.05 and 2 ng/mg for all substances. The limit of detection ranged from 0.02 to 0.03 ng/mg, and the limit of quantification was 0.05 ng/mg. The application of the method to samples of teeth obtained from drug addicts was successful. It can be applied in post-mortem cases, especially when limited amounts of sample are available. PMID- 27681341 TI - Improved Analytical Approach Based on QuECHERS/UHPLC-PDA for Quantification of Fluoxetine, Clomipramine and their Active Metabolites in Human Urine Samples. AB - This paper reports, for the first time, the development of a modified Quick, Easy, Cheap Effective, Rugged and Safe (QuEChERS) combined with a dispersive SPE (d-SPE) based clean-up procedure as a new and powerful strategy for the simultaneous and efficient isolation of two different antidepressants, fluoxetine and clomipramine, and their active metabolites in human urine samples. A univariate experimental design with four independent variables such as sample volume, extraction solvent, buffered salts and clean-up step, was performed and used to investigate the effect of process variables on the extraction efficiency. Good linearity was achieved at the studied concentration range (0.1-5.0 ug mL-1), with correlation coefficients (R2) higher than 0.9961. Low detection limits, ranging between 0.060 and 0.092 MUg mL-1 were obtained for all analytes, whereas the lowest quantification limit was 0.1 MUg mL-1, corresponding to the lowest concentration of the standard curve. The method also showed good results for accuracy, with values ranging from 91% to 105%. Intra- and inter-day precision, expressed as the relative standard deviation (RSD), were also satisfactory (<10%). Consistent recoveries of antidepressants ranging from 86% to 109% were observed when urine samples were fortified at three concentrations, namely 0.1, 2.5 and 5.0 MUg mL-1 In order to evaluate the proposed method for clinical use, the QuEChERS/UHPLC-PDA method was applied to analysis of 12 urine samples from depressed patients. PMID- 27681342 TI - Hair Analysis to Monitor the Illegal Use of Salbutamol in Beef Cattle. AB - This study measured the concentrations of salbutamol residues in red and white hair of cattle during and after salbutamol administration. Three Chinese Simmental beef cattle received an oral administration of 150 MUg/kg body weight/d salbutamol for 21 consecutive days. Salbutamol concentrations were determined on Days 1, 7, 14, and 21 of administration and on Days 7, 14, 28, 42, and 70 following the last administration dose using ultra-performance liquid chromatography-tandem mass spectrometry. The concentrations of salbutamol that eluted from hair were determined. The results revealed that salbutamol concentrations were higher in red hair than in white hair on the same sampling day (P < 0.01). In red hair, salbutamol concentrations increased from 29.82 +/- 1.8 ng/g on Day 1 of administration to 442.55 +/- 250.29 ng/g on Day 21 of administration, and decreased to 33.36 +/- 19.22 ng/g on Day 70 after the last administration. In white hair, salbutamol concentrations changed from 4.25 +/- 0.32 ng/g on Day 1 of administration to 33.81 +/- 6.44 ng/g and 12.25 +/- 2.51 ng/g on Days 14 and 70, respectively, after the last administration. The concentrations of salbutamol that eluted from white hair on Days 1 and 7 were 22.94 +/- 2.00 ng/g and 92.94 +/- 22.49 ng/g, respectively. Our findings revealed that hair is an appropriate biological matrix for assessing the illegal use of salbutamol in animal husbandry. PMID- 27681343 TI - A Fast and Comprehensive Analysis of 32 Synthetic Cannabinoids Using Agilent Triple Quadrupole LC-MS-MS. AB - Synthetic cannabinoids are a group of psychoactive compounds that mimic the effects of Delta9-tetrahydrocannabinol, the primary psychoactive constituent of marijuana (Cannabis sativa L). The Drug Enforcement Administration has classified many of the most common cannabinoids as Schedule 1 controlled substances. As a result, several novel synthetic cannabinoid series have emerged in the illicit drug market, including PINACA, FUBINACA, PB-22, AKB-48 and multiple derivatives of these compounds. Our laboratory developed and validated an analytical method for the analysis 32 synthetic cannabinoid metabolites in urine samples. Included in this method are metabolites that are constituents of the new generation of synthetic cannabinoids. Following enzymatic hydrolysis, target analytes were recovered by liquid-liquid extraction utilizing 1-chlorobutane:isopropyl alcohol (70:30) as the organic ratio. Chromatographic separation and detection was achieved using an Agilent Technologies 1290 liquid chromatograph coupled to a 6460-triple quadrupole mass spectrometer with a Jetstream electrospray source. Linearity for all analytes was established along the range of 0.5-200 ng/mL. Both intraday and interday accuracy and precision data were all within acceptable limits, +/-20% error and +/-15% relative standard deviation, respectively. Recovery ranged from 48% to 104%. This method has shown to be selective and specific, providing no evidence of interference or carryover concerns. Finally, 11 distinct synthetic cannabinoids were detected in 23 of 25 donor samples analyzed with the method. The data presented here represents a validated liquid chromatography tandem mass spectrometry method to accurately identify and quantitate synthetic cannabinoid metabolites in urine samples, incorporating new generation derivatives. PMID- 27681344 TI - Evaluation of Ethyl Glucuronide and Ethyl Sulfate in Calliphora Vicina as Potential Biomarkers for Ethanol Intake. AB - Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are specific and sensitive biomarkers for the diagnosis of acute or chronic alcohol abuse. Due to postmortem alcohol production in biological tissues, they have recently been evaluated as potential biomarkers of ethanol ingestion. This in vitro study aimed to evaluate all developmental stages of the fly Calliphora vicina L. (Calliphoridae). Different pig substrates were used during the in vitro experiments to rear C. vicina Experiments were performed to: (i) assess the presence of EtG and EtS in larvae, pupae and insects; (ii) study variability due to the substrates characteristics; (iii) evaluate the possibility of false positives due to external alcohol contamination; and (iv) estimate the potential metabolism of ethanol by the insects. EtS was found in all of the samples where the standard was added to the substrate. Muscle provided the most reliable results. EtS was found in larvae, pupae and puparia. EtG and EtS were found in larvae and pupae collected from the body of an alcoholic found dead in his home. This study showed that maggots, pupae and puparia could be a useful matrix for the evaluation of antemortem alcohol ingestion. PMID- 27681345 TI - Estimating the effects of maternal education on child dental caries using marginal structural models: The Longitudinal Study of Indigenous Australian Children. AB - OBJECTIVE: To estimate the effect of mothers' education on Indigenous Australian children's dental caries experience while controlling for the mediating effect of children's sweet food intake. METHODS: The Longitudinal Study of Indigenous Children is a study of two representative cohorts of Indigenous Australian children, aged from 6 months to 2 years (baby cohort) and from 3.5 to 5 years (child cohort) at baseline. The children's primary caregiver undertook a face-to face interview in 2008 and repeated annually for the next 4 years. Data included household demographics, child health (nutrition information and dental health), maternal conditions and highest qualification levels. Mother's educational level was classified into four categories: 0-9 years, 10 years, 11-12 years and >12 years. Children's mean sweet food intake was categorized as <20%, 20-30%, and >30%. After multiple imputation of missing values, a marginal structural model with stabilized inverse probability weights was used to estimate the direct effect of mothers' education level on children's dental decay experience. RESULTS: From 2008 to 2012, complete data on 1720 mother-child dyads were available. Dental caries experience for children was 42.3% over the 5-year period. The controlled direct effect estimates of mother's education on child dental caries were 1.21 (95% CI: 1.01-1.45), 1.03 (95% CI: 0.91-1.18) and 1.07 (95% CI: 0.93-1.22); after multiple imputation of missing values, the effects were 1.21 (95% CI: 1.05-1.39), 1.06 (95% CI: 0.94-1.19) and 1.06 (95% CI: 0.95 1.19), comparing '0-9', '10' and '11-12' years to > 12 years of education. CONCLUSION: Mothers' education level had a direct effect on children's dental decay experience that was not mediated by sweet food intake and other risk factors when estimated using a marginal structural model. PMID- 27681346 TI - The effect of 20-hydroxyecdysone on the susceptibility of Escherichia coli to different antibiotics. AB - AIMS: The aim of this study was to investigate the influence of 20 hydroxyecdysone (20E) on the susceptibility of growing Escherichia coli to antibiotics. METHODS AND RESULTS: Susceptibility of E. coli to antibiotics in the presence of 20E was estimated by determination of the colony-forming ability and the specific growth rate. Pretreatment with 20E decreased the bactericidal effect of ciprofloxacin (0.3 and 3.0 MUg ml-1 ), streptomycin (10 and 40 MUg ml-1 ) and kanamycin (10 MUg ml-1 ) and increased the bactericidal action of 0.03 MUg ml-1 ciprofloxacin. To study the influence of 20E on gene expression, we used strains of E. coli carrying fusions of promoters of relevant genes with the structural gene of beta-galactosidase. 20E had no marked effect on the expression of antioxidant genes katG, katE, sodA and the rpoS gene (general stress response), while it (alone or combined with ciprofloxacin) markedly stimulated expression of the sulA gene belonging to the SOS regulon (DNA damage response). CONCLUSION: In growing E. coli, 20E modulated the bactericidal action of antibiotics and stimulated the SOS response. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study may be used to enhance the efficiency of antibacterial therapies. PMID- 27681347 TI - Dermoscopic diagnosis of amelanotic/hypomelanotic melanoma. PMID- 27681348 TI - Enucleation for haemophthalmus secondary to choroidal neovascularisation in polypoidal choroidal vasculopathy: a therapeutic and diagnostic dilemma. AB - We report a case of enucleation for painful blind eye secondary to recurrent bleeding from choroidal neovascularisation in an eye that was irradiated following presumed metastatic breast carcinoma to the choroid. A 58-year-old woman with a history of treated breast malignancy presented with haemophthalmus and intractable glaucoma in the right eye. One year previously she had presented with right vitreous haemorrhage with subretinal mass that had been irradiated given her history of breast carcinoma. Following irradiation, vitrectomy was performed to clear the blood. Intraoperative and postoperative angiography findings suggested a diagnosis of breakthrough bleeding secondary to polypoidal choroidal vasculopathy. At this presentation, however, the intraocular bleeding was recurrent resulting in elevated intraocular pressure and pain. Despite repeat surgery and medical therapy, the eye had to be enucleated. Histopathology showed choroidal neovascularisation. PMID- 27681349 TI - Peripheral nerve involvement in classic homocystinuria: an unusual association. AB - Classic homocystinuria is one of the most common causes of hereditary hyperhomocysteinemia. It is an autosomal recessive and multisystemic disorder due to cystathionine beta-synthase deficiency. We described a case of an 18-year-old Portuguese man with an ischaemic stroke, who was subsequently diagnosed with classic homocystinuria [Thr191Met (c.572C>T) CBS mutation] associated with a sensorimotor neuropathy. The patient had a good clinical and metabolic response to pyridoxine plus methionine-restricted diet after 12 months of treatment. Neurophysiological re-evaluation with nerve conduction studies disclosed an improvement on the peripheral nerve lesion. Central nervous system manifestations in classic homocystinuria have been well documented, but this is to the best of our knowledge the first report of an association with peripheral neuropathy, which improved after hyperhomocysteinemia treatment. PMID- 27681350 TI - Spontaneous renal calyceal and ureteric rupture secondary to intravenous contrast during computed tomography intravenous pyelogram. AB - Upper urinary tract rupture in the absence of trauma is typically related to ureteric calculi causing obstructive nephropathy. Spontaneous extravasation of contrast during CT intravenous pyelography (CT IVP) is infrequently reported. Two cases, who underwent CT IVP to further investigate positive urine cytology and microscopic haematuria, respectively, are described here. In both cases, there was spontaneous extravasation of contrast seen in the postcontrast scans in the absence of ureteric calculi or hydronephrosis which is very unusual. PMID- 27681351 TI - Loperamide-induced hypopituitarism. AB - Loperamide is the most commonly used antidiarrhoeal medication in the UK. We report a serious and hitherto undocumented adverse effect of chronic use in a 45 year-old man with inflammatory bowel disease. He presented to the endocrine clinic with fatigue and low libido; biochemical assessment revealed hypogonadism and adrenal insufficiency without any elevated adrenocorticotropic hormone. When symptoms allowed, loperamide was reduced and a short synacthen test (SST) showed a 'clear pass' with a normal peak cortisol of 833 nmol/L. Later, worsening diarrhoea necessitated an escalation in loperamide use again. While taking a daily dose of 15-20 mg (recommended daily maximum 16 mg) reassessment revealed a fall in peak cortisol on SST to 483 nmol/L, a subnormal response. Clinicians should exercise caution when relying on loperamide to manage their patients' chronic diarrhoea and remain mindful of the possibility of drug-induced life threatening adrenal insufficiency. PMID- 27681352 TI - Atypical presentation of acute fulminant neonatal necrotising enterocolitis: diagnostic superiority of sonographic evaluation over plain radiography of abdomen. AB - A female preterm infant was born to a non-consanguineous couple at 35 weeks of gestation. On day 8 of life, while on full feeds, she developed prolonged apnoea and bradycardia, requiring respiratory support. Her abdomen was soft with unremarkable serial abdominal X-rays. Her septic screen was negative. Metabolic acidosis was worsening despite treatment. Echocardiography showed evidence of high pulmonary pressures. With further deterioration, an ultrasound scan of the abdomen was requested in view of the rising suspicion of abdominal pathology in the absence of sepsis and metabolic disorders. Mural oedema, pneumatosis and portal venous gas, consistent with diagnosis of necrotising enterocolitis, were noted in the ultrasound images. An emergency laparotomy showed extensive small bowel necrosis. Despite maximal medical support, the infant died. This case highlights the importance of imaging using an ultrasound scanner in the diagnosis of necrotising enterocolitis in preterm infants having intractable metabolic acidosis, subtle abdominal signs and unremarkable abdominal X-rays. PMID- 27681353 TI - XIAP deficiency and MEFV variants resulting in an autoinflammatory lymphoproliferative syndrome. AB - A 16-year-old boy of Caucasian ethnicity was evaluated for recurrent febrile episodes occurring during most of his life without establishment of any microbial aetiology. During febrile episodes he developed extensive splenomegaly, lymphadenopathy, anaemia, severe abdominal pain and general malaise. Lymph node biopsies demonstrated inflammation and sinus histiocytosis but no malignancy or granuloma. The patient underwent seroconversion for Epstein-Barr virus (EBV) infection during the hospitalisation. Genetic testing identified a hemizygous frameshift mutation in the X linked inhibitor of apoptosis (XIAP)-gene as well as variants in the MEFV gene indicating Familial Mediterranean Fever (FMF). XIAP expression was markedly reduced in the patient, while a functional assay assessing tumour necrosis factor (TNF)alpha production of monocytes in response to NOD2 stimulation displayed reduced activity. We suggest that the heterozygous MEFV variants and the hemizygous XIAP variant in combination triggered the prolonged and pathological inflammatory response to EBV infection. PMID- 27681354 TI - Diagnosis and management of intersection syndrome as a cause of overuse wrist pain. AB - Wrist pain due to repetitive motion or overuse is a common presentation in primary care. This case reports the rare condition of intersection syndrome as the cause of the wrist pain in an amateur tennis player. This is a non infectious, inflammatory process that occurs where tendons in the first extensor compartment intersect the tendons in the second extensor compartment. Suitable history and examination provided the diagnosis, which was confirmed by MRI. Management consisted of early involvement of the multidisciplinary team, patient education, workplace and sporting adaptations, rest, analgesia, reduction of load, protection and immobilisation of the affected joint followed by a period of rehabilitation. PMID- 27681355 TI - Hepatic hydatid disease presenting as secondary Budd-Chiari syndrome. PMID- 27681356 TI - Two atypical cases of isolated migrainous paraesthesia. AB - A large number of migraineurs have various transient neurological symptoms in the absence of headache at one time or another. Such transient neurological symptoms largely represent the typical migraine auras without headaches. Isolated visual aura is the most common aura in this category. Sensory aura is the second most common aura. However, the literature is sparse regarding isolated sensory aura without headache. Herein, we are reporting two cases of recurrent paraesthesia that fulfilled the International Classification of Headache Disorders (ICHD 3beta) criteria of typical migrainous sensory aura without headache. Review of the literature suggests that upper limb involvement is almost universal (>90%) in the typical sensory aura. However, our both cases were unusual in this aspect. Case 1 had recurrent spontaneous paraesthesia predominantly on the left side of the face. Case 2 had recurrent spontaneous paraesthesia in either the left or right lower limb. Both cases responded to antimigraine drugs. PMID- 27681357 TI - Seroprevalence of Trichinella infections in domestic dogs from Slovakia. AB - Trichinellosis is constantly present in the sylvatic cycle in Slovakia, with several sporadic human outbreaks registered since the 1960s. The largest outbreak of trichinellosis occurred in 1998 and was related to the consumption of dog meat that had been added to smoked pork sausages. The aim of this study was to estimate the seroprevalence of Trichinella infection in domestic dogs in various regions of Slovakia. Out of 439 dogs tested, 56 (12.8%) were classified as a seropositive based on the enzyme-linked immunosorbent assay (ELISA), with confirmation by Western blotting. The highest seropositivity was recorded among dogs from the eastern part of Slovakia, in the Presov (22.9%) and Kosice (17.1%) regions, long considered to be highly endemic for Trichinella occurrence and where the prevalence of infection in the vulpine population is also the highest in Slovakia. Trichinella-seropositive animals were detected significantly more often in dogs kept in rural areas (21.1%) when compared with animals living in towns or suburban localities (7.7%). On the other hand, neither age, nor gender and size of the dogs were shown to be a significant factor for Trichinella infection (P > 0.05). The present results indicate that the dog population in Slovakia is at high risk of exposure to Trichinella parasites and could potentially represent a suitable host group for serological monitoring of Trichinella infection as convenient sentinel animals. PMID- 27681359 TI - The end of the wormwars? PMID- 27681360 TI - Targeting of sebaceous glands to treat acne by micro-insulated needles with radio frequency in a rabbit ear model. AB - BACKGROUND AND OBJECTIVES: Many studies have investigated the application of micro-insulated needles with radio frequency (RF) to treat acne in humans; however, the use of a micro-insulated needle RF applicator has not yet been studied in an animal model. The purpose of this study was to evaluate the effectiveness of a micro-insulated needle RF applicator in a rabbit ear acne (REA) model. STUDY DESIGN/MATERIALS AND METHODS: In this study, we investigated the effect of selectively destroying the sebaceous glands using a micro-insulated needle RF applicator on the formation of comedones induced by application of 50% oleic acid and intradermal injection of P. acnes in the orifices of the external auditory canals of rabbits. The effects of the micro-insulated needle RF applicator treatment were evaluated using regular digital photography in addition to 3D Primos imaging evaluation, Skin Visio Meter microscopic photography, and histologic analyses. RESULTS: Use of the micro-insulated needle RF applicator resulted in successful selective destruction of the sebaceous glands and attenuated TNF-alpha release in an REA model. The mechanisms by which micro insulated needles with RF using 1 MHz exerts its effects may involve inhibition of comedone formation, triggering of the wound healing process, and destruction of the sebaceous glands and papules. CONCLUSION: The use of micro-insulated needles with RF applicators provides a safe and effective method for improving the appearance of symptoms in an REA model. The current in vivo study confirms that the micro-insulated needle RF applicator is selectively destroying the sebaceous glands. Lasers Surg. Med. 49:395-401, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27681358 TI - Genome privacy: challenges, technical approaches to mitigate risk, and ethical considerations in the United States. AB - Accessing and integrating human genomic data with phenotypes are important for biomedical research. Making genomic data accessible for research purposes, however, must be handled carefully to avoid leakage of sensitive individual information to unauthorized parties and improper use of data. In this article, we focus on data sharing within the scope of data accessibility for research. Current common practices to gain biomedical data access are strictly rule based, without a clear and quantitative measurement of the risk of privacy breaches. In addition, several types of studies require privacy-preserving linkage of genotype and phenotype information across different locations (e.g., genotypes stored in a sequencing facility and phenotypes stored in an electronic health record) to accelerate discoveries. The computer science community has developed a spectrum of techniques for data privacy and confidentiality protection, many of which have yet to be tested on real-world problems. In this article, we discuss clinical, technical, and ethical aspects of genome data privacy and confidentiality in the United States, as well as potential solutions for privacy-preserving genotype phenotype linkage in biomedical research. PMID- 27681361 TI - Influence of preoperative pain in the success rate of indirect pulp capping: a retrospective study. AB - BACKGROUND: The association of preoperative pain and indirect pulp treatment in permanent teeth is still unknown. This study aimed to evaluate the influence of preoperative pain in the success rate of indirect pulp capping. METHODS: The sample of this retrospective study was constituted for 133 teeth treated in a Private clinic in Joinvile, Brazil, by one experienced dentist between 2007 and 2012. Data related to clinical and demographic variables that could influence in the success rate of indirect pulp capping were also collected, such patient age and sex, type of teeth and arch. Chi-square test was used to evaluate the association between preoperative pain with postoperative one and success of the treatment. Logistic regression was performed to identify significant clinical and demographical factors associated with the success of the indirect pulp capping. RESULTS: The overall success rate was 100% in the absence of preoperative pain. However, when the preoperative pain was present, the failure rate was 18.3%. Statistical analysis showed significant association between preoperative pain and postoperative one and failure rate of the indirect pulp capping. The other independent variables were not associated with the success rate of the treatment. CONCLUSIONS: The presence of preoperative pain is associated with the decrease of the success rate of indirect pulp capping. PMID- 27681362 TI - First report of Escherichia coli co-producing NDM-1 and OXA-232. AB - Recently Gram-negative bacteria co-producing multiple carbapenemases have emerged in different parts of the world. We report the first isolation of an Escherichia coli strain co-producing the carbapenemases NDM-1 and OXA-232. PMID- 27681364 TI - Zinc-Containing Restorations Create Amorphous Biogenic Apatite at the Carious Dentin Interface: A X-Ray Diffraction (XRD) Crystal Lattice Analysis. AB - The aim of this research was to assess the ability of amalgam restorations to induce amorphous mineral precipitation at the caries-affected dentin substrate. Sound and caries-affected dentin surfaces were subjected to both Zn-free and Zn containing dental amalgam restorations. Specimens were submitted to thermocycling (100,000 cycles/5 degrees C-55 degrees C, 3 months). Dentin surfaces were studied by atomic force microscopy (nanoroughness), X-ray diffraction, field emission scanning electron microscopy, and energy-dispersive analysis, for physical and morphological surface characterization. Zn-containing amalgam placement reduced crystallinity, crystallite size, and grain size of calcium phosphate crystallites at the dentin surface. Both microstrain and nanoroughness were augmented in caries-affected dentin restored with Zn-containing amalgams. Caries-affected dentin showed the shortest mineral crystallites (11.04 nm), when Zn-containing amalgams were used for restorations, probably leading to a decrease of mechanical properties which might favor crack propagation and deformation. Sound dentin restored with Zn-free amalgams exhibited a substantial increase in length of grain particles (12.44 nm) embedded into dentin crystallites. Zn-containing amalgam placement creates dentin mineralization and the resultant mineral was amorphous in nature. Amorphous calcium phosphate provides a local ion-rich environment, which is considered favorable for in situ generation of prenucleation clusters, promotong further dentin remineralization. PMID- 27681363 TI - Prevalence and quinolone resistance of fecal carriage of extended-spectrum beta lactamase-producing Escherichia coli in 6 communities and 2 physical examination center populations in Shanghai, China. AB - OBJECTIVES: To characterize extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates from the community, determine their antibiotic sensitivity profiles and quinolone resistance mechanisms, and identify any horizontal transfer of ESBL genes. METHODS: One thousand seven hundred thirty-two stool samples were collected from healthy individuals in 6 communities and 2 physical examination centers in Shanghai, China. ESBL-producing E. coli was screened and confirmed by confirmatory test and E. coli-identifying agars. PCR was used to amplify ESBL-encoding genes blaCTX-M, blaTEM, blaSHV genes, and quinolone resistance-relating genes gyrA, gryB, parC, parE, qnrS, aac (6')-Ib-cr, oqxA, and oqxB, followed by sequencing. Antimicrobial susceptibility tests and conjugation assays were also performed. RESULTS: Overall, 528 isolates were identified as ESBL-producing E. coli, and all were positive for blaCTX-M. CTX-M 14 was found most frequently (48.9%). S83L+/-D87N in gyrA and S80I in parC were the most common topoisomerase mutations. Plasmid-mediated quinolone resistance (PMQR) determinants were also detected, including qnrS1 (11.7%), qnrS2 (3.7%), aac (6')-Ib-cr(12.8%), oqxA(8.5%), and oqxB(11.0%). The rate of multidrug resistance was very high (92.2%). ESBL genes transferred successfully in 39.4% isolates. CONCLUSIONS: There is a high prevalence of fecal carriage of ESBL producing E. coli in the community in Shanghai, with high-level quinolone resistance and CTX-M-14 being the predominant CTX-M enzyme. PMID- 27681365 TI - Correction to "Recognition of Poly-Ubiquitins by the Proteasome through Protein Refolding Guided by Electrostatic and Hydrophobic Interactions". PMID- 27681366 TI - One-Pot Synthesis of Superfine Core-Shell Cu@metal Nanowires for Highly Tenacious Transparent LED Dimmer. AB - We demonstrate a one-pot, low-cost, and scalable method for fast synthesis of superfine and uniform core-shell Cu nanowires (NWs) coated with optional metals and/or alloy. Cu NWs in high aspect ratio (>3000) were synthesized through an oleylamine-mediated solution method, and tunable shell coating was performed by injecting metal-organic precursors at the last stage of reaction. Superfine Cu@metal NWs (Ti, Zn, V, Ni, Ag, NiZn, etc) were achieved in diameter of ~30 nm and length of ~50 MUm. Transparent conductive films were obtained by imprinting method, showing high optoelectronic performance (51 Omega/sq at 93% transmittance), high mechanical tenacity over bending, twisting, stretching, and compressing, and robust antioxidant ability (high temperature and high humidity). A transparent film dimmer for light-emitting diode (LED) lighting was fabricated with the stretchable Cu@Ti NWs network. The LED luminance could be accurately tuned by the deformation strain of Cu@Ti NWs film. PMID- 27681367 TI - Molecular Ferroelectric with Most Equivalent Polarization Directions Induced by the Plastic Phase Transition. AB - Besides the single crystals, ferroelectric materials are actually widely used in the forms of the polycrystals like ceramics. Multiaxial ferroelectrics with multiple equivalent polarization directions are preferable for such applications, because more equivalent ferroelectric axes allow random spontaneous polarization vectors to be oriented along the electric field to achieve a larger polarization after poling. Most of ceramic ferroelectrics like BaTiO3 have equivalent ferroelectric axes no more than three. We herein describe a molecular-ionic ferroelectric with 12 equivalent ferroelectric axes: tetraethylammonium perchlorate, whose number of axes is the most in the known ferroelectrics. Appearance of so many equivalent ferroelectric axes benefits from the plastic phase transition, because the plastic phase usually crystallizes in a highly symmetric cubic system. A perfect macroscopic ferroelectricity can be obtained on the polycrystalline film of this material. This finding opened an avenue constructing multiaxial ferroelectrics for applications as polycrystalline materials. PMID- 27681368 TI - Reduced Long-Term Relative Survival in Females and Younger Adults Undergoing Cardiac Surgery: A Prospective Cohort Study. AB - OBJECTIVES: To assess long-term survival and mortality in adult cardiac surgery patients. METHODS: 8,564 consecutive patients undergoing cardiac surgery in Trondheim, Norway from 2000 until censoring 31.12.2014 were prospectively followed. Observed long-term mortality following surgery was compared to the expected mortality in the Norwegian population, matched on gender, age and calendar year. This enabled assessment of relative survival (observed/expected survival rates) and relative mortality (observed/expected deaths). Long-term mortality was compared across gender, age and surgical procedure. Predictors of reduced survival were assessed with multivariate analyses of observed and relative mortality. RESULTS: During follow-up (median 6.4 years), 2,044 patients (23.9%) died. The observed 30-day, 1-, 3- and 5-year mortality rates were 2.2%, 4.4%, 8.2% and 13.8%, respectively, and remained constant throughout the study period. Comparing observed mortality to that expected in a matched sample from the general population, patients undergoing cardiac surgery showed excellent survival throughout the first seven years of follow-up (relative survival >= 1). Subsequently, survival decreased, which was more pronounced in females and patients undergoing other procedures than isolated coronary artery bypass grafting (CABG). Relative mortality was higher in younger age groups, females and patients undergoing aortic valve replacement (AVR). The female survival advantage in the general population was obliterated (relative mortality ratio (RMR) 1.35 (1.19-1.54), p<0.001). Increasing observed long-term mortality seen with ageing was due to population risk, and younger age was independently associated with increased relative mortality (RMR per 5 years 0.81 (0.79-0.84), p<0.001)). CONCLUSIONS: Cardiac surgery patients showed comparable survival to that expected in the general Norwegian population, underlining the benefits of cardiac surgery in appropriately selected patients. The beneficial effect lasted shorter in younger patients, females and patients undergoing AVR or other procedures than isolated CABG. Thus, the study identified three groups that need increased attention for further improvement of outcomes. PMID- 27681370 TI - Myelin-related gene silencing mediated by LPA1 - Rho/ROCK signaling is correlated to acetylation of NFkappaB in S16 Schwann cells. AB - Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA1-type receptor-mediated down-regulation of myelin related molecules, such as MBP and MPZ. In this study using S16 mature-type Schwann cells, we found that LPA-induced down-regulation of myelin-related genes is attributed by the activation of LPA1 receptor, Rho kinase, and p300, leading to an acetylation of NFkappaB, which down-regulates the transcription of Sox10, MBP and MPZ genes. PMID- 27681369 TI - Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity. AB - The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec 9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass. PMID- 27681372 TI - Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats. AB - Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice. In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella(r) in comparison with subcutaneous buprenorphine administration. By exposing the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella(r) were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration ( P < 0.01), although antinociceptive effects were not as marked as with subcutaneous administration, and had a later onset. It is advised to administer the oral formulation of buprenorphine in Nutella(r) in a 10-fold higher dose, as well as approximately 60 min earlier, than with the more commonly employed subcutaneous route of administration. PMID- 27681371 TI - LUTE (Local Unpruned Tuple Expansion): Accurate Continuously Flexible Protein Design with General Energy Functions and Rigid Rotamer-Like Efficiency. AB - Most protein design algorithms search over discrete conformations and an energy function that is residue-pairwise, that is, a sum of terms that depend on the sequence and conformation of at most two residues. Although modeling of continuous flexibility and of non-residue-pairwise energies significantly increases the accuracy of protein design, previous methods to model these phenomena add a significant asymptotic cost to design calculations. We now remove this cost by modeling continuous flexibility and non-residue-pairwise energies in a form suitable for direct input to highly efficient, discrete combinatorial optimization algorithms such as DEE/A* or branch-width minimization. Our novel algorithm performs a local unpruned tuple expansion (LUTE), which can efficiently represent both continuous flexibility and general, possibly nonpairwise energy functions to an arbitrary level of accuracy using a discrete energy matrix. We show using 47 design calculation test cases that LUTE provides a dramatic speedup in both single-state and multistate continuously flexible designs. PMID- 27681374 TI - Hospital preferences of nursing students in Korea: a discrete choice experiment approach. AB - BACKGROUND: DCE was applied to investigate nursing students' preferred hospital choice criteria and to investigate the trends in the trade-offs by calculating the marginal rate of substitution between these criteria. This study identified the properties of the hospitals primarily selected by nursing students, and aims to estimate the monetary value of each attribute. METHODS: Based on discussions and in-depth interviews with nursing students' focus groups and a literature review, we created a discrete choice experiment (DCE) that assessed how students' stated preference for a certain hospital choice was influenced by various job attributes: higher salary, location, hospital type, salary per year, provision of a dormitory, etc. We applied this DCE to nursing students in South Korea using a brief structured questionnaire, and we used conditional logit models to estimate the utility of each job's attributes. Willingness to pay (WTP) was estimated as the ratio of the value of the coefficient of interest to the negative of the cost attribute. RESULTS: Complete data for the DCE analysis were available for 702 nursing students. In the main effect mixed logit model, the welfare system and organizational culture were most strongly associated with job preference. Location, hospital type, and opportunity to upgrade qualifications had a negative influence on hospital choice. The WTP threshold was 7,043,000 KRW for the welfare system and 9,928,000 KRW for the organizational culture (relation-oriented). CONCLUSIONS: Better nursing working conditions, such as a positive organizational culture and the provision of a welfare system, can improve the motivation and applications for hospitals in rural areas. PMID- 27681373 TI - Dose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy. AB - Alternative splicing is a regulated process that results in expression of specific mRNA and protein isoforms. Alternative splicing factors determine the relative abundance of each isoform. Here we focus on MBNL1, a splicing factor misregulated in the disease myotonic dystrophy. By altering the concentration of MBNL1 in cells across a broad dynamic range, we show that different splicing events require different amounts of MBNL1 for half-maximal response, and respond more or less steeply to MBNL1. Motifs around MBNL1 exon 5 were studied to assess how cis-elements mediate the MBNL1 dose-dependent splicing response. A framework was developed to estimate MBNL concentration using splicing responses alone, validated in the cell-based model, and applied to myotonic dystrophy patient muscle. Using this framework, we evaluated the ability of individual and combinations of splicing events to predict functional MBNL concentration in human biopsies, as well as their performance as biomarkers to assay mild, moderate, and severe cases of DM. PMID- 27681375 TI - Midterm outcomes of high-flexion total knee arthroplasty on Japanese lifestyle. AB - OBJECTIVE: To evaluate the clinical outcomes after total knee arthroplasty (TKA) using the Genesis II posterior stabilized prosthesis with a high-flex insert during the mid-term follow-up and to assess its effect on the Japanese lifestyle. MATERIALS AND METHODS: Fifty-three consecutive patients (8 men and 45 women) underwent primary TKA. The mean follow-up time was 76 months (5-9 years). Clinical results were assessed with the Japanese Orthopedic Association osteoarthritis knee rating score (JOA knee score), range of motion, and lifestyle changes. RESULTS: The postoperative JOA knee score improved significantly compared to the preoperative JOA knee score. The mean preoperative flexion range improved from 112 degrees to 123 degrees postoperatively (p < 0.05). Additionally, our findings showed that 39% of patients enjoyed a floor-sitting life preoperatively, but only 30% of patients enjoyed floor-sitting life postoperatively. CONCLUSION: The postoperative range of knee motion and JOA knee score improved after TKA using the Genesis II posterior stabilized prosthesis with a high-flex insert, but the number of patients who enjoyed floor-sitting life decreased from 39% to 30% because of feelings of fear and discomfort. LEVEL OF EVIDENCE: Level IV, Therapeutic study. PMID- 27681376 TI - Prospective study of postoperative whole breast radiotherapy for Japanese large breasted women: a clinical and dosimetric comparisons between supine and prone positions and a dose measurement using a breast phantom. AB - BACKGROUND: This prospective study aimed to compare dose volume histograms (DVH) of the breasts and organs at risk (OARs) of whole breast radiotherapy in the supine and prone positions, and frequency and severity of acute and late toxicities were analyzed. METHODS: Early-stage breast cancer patients with large breasts (Japanese bra size C or larger, or the widest measurements of the bust >= 95 cm) undergoing partial mastectomy participated in this study. CT-based treatment plans were made in each position, and various dosimetric parameters for the breast and OARs were calculated to compare the supine and prone radiotherapy plans. The actual treatment was delivered in the position regarded as better. RESULTS: From 2009 to 2010, 22 patients were prospectively accrued. Median follow up period was 58 months. The homogeneity index and lung doses were significantly lower in the prone position (P = 0.008, P < 0.0001 and P < 0.0001, respectively). Cardiac dose showed no significant differences between two positions. By comparing two plans, the prone position was chosen in 77 % of the patients. In the prone position, >= grade 2 acute dermatitis were seen in 47 % of patients treated, whereas 20 % of the patients treated in the supine position had grade 2 and no cases of grade 3, although without a statistical significance of the rates of >= grade 2 acute dermatitis between the two positions (P = 0.28). The actual dose measurement using a breast phantom revealed significantly higher surface dose of the breast treated in the prone position than that in the supine position. CONCLUSIONS: Breast irradiation in the prone position improves PTV homogeneity and lowers doses to the OARs in the Japanese large-breast patients. However meticulous positioning of the breast in the prone board avoiding the bolus effect is necessary to prevent acute dermatitis. PMID- 27681377 TI - Investigation of Streptococcus salivarius-mediated inhibition of pneumococcal adherence to pharyngeal epithelial cells. AB - BACKGROUND: Pneumococcal adherence to the nasopharyngeal epithelium is a critical step in colonisation and disease. The probiotic bacterium, Streptococcus salivarius, can inhibit pneumococcal adherence to epithelial cells in vitro. We investigated the mechanism(s) of inhibition using a human pharyngeal epithelial cell line (Detroit 562) following pre-administration of two different strains of S. salivarius. RESULTS: Whilst the bacteriocin-encoding megaplasmids of S. salivarius strains K12 and M18 were essential to prevent pneumococcal growth on solid media, they were not required to inhibit pneumococcal adherence. Experiments testing S. salivarius K12 and two pneumococcal isolates (serotypes 19F and 6A) showed that inhibition of 19F may involve S. salivarius-mediated blocking of pneumococcal binding sites: a negative correlation was observed between adherence of K12 and 19F, and no inhibition occurred when K12 was prevented from contacting epithelial cells. K12-mediated inhibition of adherence by 6A may involve additional mechanisms, since no correlation was observed between adherence of K12 and 6A, and K12 could inhibit 6A adherence in the absence of cell contact. CONCLUSIONS: These results suggest that S. salivarius employs several mechanisms, including blocking pneumococcal binding sites, to reduce pneumococcal adherence to pharyngeal epithelial cells. These findings extend our understanding of how probiotics may inhibit pneumococcal adherence and could assist with the development of novel strategies to prevent pneumococcal colonisation in the future. PMID- 27681378 TI - Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma. AB - There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8 T-cell responses in this well established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 hours after injection, 26.5%+/-16.9% of the injected PG-CpG dose versus 4.72%+/-2.61% of free CpG remained at the tumor, and 1.53%+/ 1.22% of the injected PG-CpG versus 0.37%+/-0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes. PMID- 27681379 TI - New insights into the mechanisms of acetic acid resistance in Acetobacter pasteurianus using iTRAQ-dependent quantitative proteomic analysis. AB - Acetobacter pasteurianus is the main starter in rice vinegar manufacturing due to its remarkable abilities to resist and produce acetic acid. Although several mechanisms of acetic acid resistance have been proposed and only a few effector proteins have been identified, a comprehensive depiction of the biological processes involved in acetic acid resistance is needed. In this study, iTRAQ based quantitative proteomic analysis was adopted to investigate the whole proteome of different acidic titers (3.6, 7.1 and 9.3%, w/v) of Acetobacter pasteurianus Ab3 during the vinegar fermentation process. Consequently, 1386 proteins, including 318 differentially expressed proteins (p<0.05), were identified. Compared to that in the low titer circumstance, cells conducted distinct biological processes under high acetic acid stress, where >150 proteins were differentially expressed. Specifically, proteins involved in amino acid metabolic processes and fatty acid biosynthesis were differentially expressed, which may contribute to the acetic acid resistance of Acetobacter. Transcription factors, two component systems and toxin-antitoxin systems were implicated in the modulatory network at multiple levels. In addition, the identification of proteins involved in redox homeostasis, protein metabolism, and the cell envelope suggested that the whole cellular system is mobilized in response to acid stress. These findings provide a differential proteomic profile of acetic acid resistance in Acetobacter pasteurianus and have potential application to highly acidic rice vinegar manufacturing. PMID- 27681380 TI - Comment on "Cut-off points to identify sarcopenia according to European Working Group on Sarcopenia in Older People (EWGSOP) definition". PMID- 27681381 TI - Day case transobturator tapes: a cut and dried solution. AB - BACKGROUND: The transobturator tape (TOT) has been utilized in the surgical management of SUI since 2001 when it was first described and is associated with minimal risk of trauma as its purely perineal insertion avoids entry to the retropubic space. Given its high success rate, low associated peri-operative morbidity and relative ease of insertion, it has been increasingly used as a day case procedure worldwide. AIM: This study aims to demonstrate the suitability of the transobturator tape (TOT) as a day surgery procedure in the Republic of Ireland. METHODS: A retrospective review of all the patients who underwent TOT as a day case procedure at a tertiary referral centre in Dublin over a 1 year period (March 2015-March 2016) was carried out. This was post the introduction of the procedure as a day case for a select group of patients. The outcomes evaluated included intraoperative and postoperative complication rates, voiding dysfunction rates, unscheduled inpatient admissions following the procedure and continence rates post-procedure. RESULTS: Fifteen cases were reviewed. There was one case with minor intraoperative complication of bladder perforation which was managed as an outpatient. One patient (6 %) failed to achieve adequate voiding within the 6-h timeframe allowed and, therefore, required overnight admission. All patients reported dryness at the 6-week review. Major elective waiting time for the gynaecology list decreased from 28 to 10 weeks 1 year post-commencement of the protocol. CONCLUSIONS: We conclude that the transobturator tape procedure is suitable as a day case in a select group of patients in the Irish healthcare setting. There was no increased rate of morbidity demonstrated in the group and readmission rates were low. It has reduced waiting times by increasing throughput of cases and ultimately will lead to reduced costs for hospitals. PMID- 27681382 TI - Allium sativum L. regulates in vitro IL-17 gene expression in human peripheral blood mononuclear cells. AB - BACKGROUND: Allium sativum L. (A.S.) "garlic", one of the most interesting medicinal plants, has been suggested to contain compounds that could be beneficial in numerous pathological situations including cancer. In this work, we aimed to assess the immunomodulatory effect of A.S. preparation on human peripheral blood mononuclear cells from healthy individuals. METHODS: Nontoxic doses of A.S. were identified using MTT assay. Effects on CD4+ or CD8+ T lymphocyte proliferation were studied using flow cytometry. The effect of A.S. on cytokine gene expression was studied using qRT-PCR. Finally, qualitative analysis of A.S. was performed by HPLC approach. Data were analyzed statistically by one way ANOVA test. RESULTS: The nontoxic doses of A.S. preparation did not affect neither spontaneous nor TCR-mediated CD4+ or CD8+ T lymphocyte proliferation. Interestingly, A.S. exhibited a statistically significant regulation of IL-17 gene expression, a cytokine involved in several inflammatory and autoimmune diseases. In contrast, the expression of IL-4, an anti-inflammatory cytokine, was unaffected. Qualitative analysis of A.S. ethanol preparation indicated the presence of three polyphenol bioactive compounds, which are catechin, vanillic acid and ferulic acid. CONCLUSION: The specific inhibition of the pro inflammatory cytokine, IL-17 without affecting cell proliferation in human PBMCs by the Allium sativum L. preparation suggests a potential valuable effect of the compounds present in this plant for the treatment of inflammatory diseases and cancer, where IL-17 is highly expressed. The individual contribution of these three compounds to this global effect will be assessed. PMID- 27681384 TI - Lowering the Bar on the Low-Fat Diet. PMID- 27681383 TI - Association between nesfatin-1 levels and metabolic improvements in severely obese patients who underwent biliopancreatic derivation with duodenal switch. AB - CONTEXT: Nesfatin-1 is a neuroendocrine peptide with potent anorexigenic activity in rodents. The potential role of nesfatin-1 on the regulation of energy balance, metabolic functions and inflammation is currently debated in obese humans. In the present study, nesfatin-1 fluctuations and their associations with metabolic factors were investigated in severely obese patients who underwent biliopancreatic diversion with duodenal switch (BPD/DS) and severely obese controls (SOC). BASIC PROCEDURES: Sixty severely obese patients who underwent BPD/DS and 15 SOC (matched for BMI and age) were included in the study. Associations between nesfatin-1 levels and body composition, glucose metabolism, lipid profile as well as inflammatory markers were evaluated at baseline and over a post-surgery12-month (12M) period. MAIN FINDINGS: Body weight was reduced at 6M and at 12M in BPD/DS patients (P<0.001). Nesfatin-1 levels were reduced at 6M (women: P<0.05) and at 12M (men and women; P<0.001) in BPD/DS patients. At baseline, nesfatin-1 levels negatively correlated with weight, fat (FM) and fat free mass (FFM) in the whole population (combined BPD/DS and SOC patients). At 12M, nesfatin-1 concentrations positively correlated with weight, FM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, triglyceride and apoB values. At 12M, % changes in nesfatin-1 were positively associated with% changes in weight, FM, FFM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, apoB and C-reactive protein. CONCLUSION: Nesfatin-1 levels decrease following BPD/DS-induced weight loss and are significantly associated with parameters of metabolic health. PMID- 27681386 TI - Xylitol as a potential co-crystal co-former for enhancing dissolution rate of felodipine: preparation and evaluation of sublingual tablets. AB - Dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization of drugs with inert material can help in this direction. The benefit will become even greater if the inert material can form co crystal while maintaining its main function as excipient. Accordingly, the objective of the current study was to investigate xylitol as a potential co crystal co-former for felodipine with the goal of preparing felodipine sublingual tablets. Co-crystallization was achieved by wet co-grinding of the crystals deposited from methanolic solutions containing felodipine with increasing molar ratios of xylitol (1:1, 1:2 and 1:3). The developed co-crystals were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) before monitoring drug dissolution. These results reflected the development of new crystalline species depending on the relative proportions of felodipine and xylitol with complete co-crystallization of felodipine being achieved in the presence of double its molar concentration of xylitol. This co-crystal formulation was compressed into sublingual tablet with ultrashort disintegration time with subsequent fast dissolution. Co-crystal formation was associated with enhanced dissolution with the optimum formulation producing the fastest dissolution rate. In conclusion, xylitol can be considered as a co-crystal co-former for enhanced dissolution rate of drugs. PMID- 27681385 TI - De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease. AB - Intellectual disabilities are genetically heterogeneous and can be associated with congenital anomalies. Using whole-exome sequencing (WES), we identified five different de novo missense variants in the protein phosphatase-1 catalytic subunit beta (PPP1CB) gene in eight unrelated individuals who share an overlapping phenotype of dysmorphic features, macrocephaly, developmental delay or intellectual disability (ID), congenital heart disease, short stature, and skeletal and connective tissue abnormalities. Protein phosphatase-1 (PP1) is a serine/threonine-specific protein phosphatase involved in the dephosphorylation of a variety of proteins. The PPP1CB gene encodes a PP1 subunit that regulates the level of protein phosphorylation. All five altered amino acids we observed are highly conserved among the PP1 subunit family, and all are predicted to disrupt PP1 subunit binding and impair dephosphorylation. Our data suggest that our heterozygous de novo PPP1CB pathogenic variants are associated with syndromic intellectual disability. PMID- 27681388 TI - Association Between Pediatric Psoriasis and Waist-to-Height Ratio in the Absence of Obesity: A Multicenter Australian Study. AB - Importance: Increasing evidence suggests that psoriasis poses a cardiometabolic risk in children, as in adults. The best way to screen for this has not yet been established. Waist-to-height ratio (WtHR) can easily identify children with increased central adiposity and is a simpler alternative to body mass index (BMI) that does not require growth charts or percentiles. Having a WtHR of 0.5 or greater is associated with future cardiovascular risk. Objective: To determine whether children with psoriasis are more likely to have increased WtHR, obesity, and metabolic syndrome relative to children without psoriasis. Design, Setting, and Participants: This multicenter cross-sectional prospective case-control study was conducted from February 7, 2014, to July 15, 2015, in a tertiary referral center pediatric dermatology clinic and in 2 private consultant rooms of specialist dermatologists, all located in Sydney and Gosford, New South Wales, Australia. Participants were children (110 girls and 98 boys) aged from 5 to 16 years, 135 children with psoriasis and 73 controls with noninflammatory skin conditions. Main Outcomes and Measures: Increased central adiposity indicated by WtHR of 0.5 or higher, metabolic syndrome, and increased BMI. Results: Of the 208 children evaluated (110 girls and 98 boys) aged from 5 to 16 years (mean age, 8.9 years), 135 had psoriasis and 73 were controls with noninflammatory skin conditions. Children with psoriasis were more likely to have increased central adiposity, with WtHR of 0.5 or greater (29% [n = 39] vs 11% [n = 8]; P = .002). Four of 53 children older than 10 years with psoriasis were found to have metabolic syndrome compared with none of 29 in the control group (8% vs 0%; P = .29). Three of 15 children with moderate to severe psoriasis had metabolic syndrome compared with 1 of 38 children with mild psoriasis (20% vs 3%; P = .06). Children with moderate to severe psoriasis had a higher mean WtHR than children with mild psoriasis (0.48 vs 0.46; P = .04). Overweight and obesity according to BMI did not vary significantly between children with psoriasis and controls (17% [n = 23] vs 16% [n = 12]; P = .91). Conclusions and Relevance: In this Australian cohort of children with psoriasis, elevated WtHR was significantly more common in patients with psoriasis than in controls, while proportions of participants with metabolic syndrome or BMI-determined obesity were not significantly different between the 2 groups. PMID- 27681387 TI - Benchmarking Sepsis Gene Expression Diagnostics Using Public Data. AB - OBJECTIVE: In response to a need for better sepsis diagnostics, several new gene expression classifiers have been recently published, including the 11-gene "Sepsis MetaScore," the "FAIM3-to-PLAC8" ratio, and the Septicyte Lab. We performed a systematic search for publicly available gene expression data in sepsis and tested each gene expression classifier in all included datasets. We also created a public repository of sepsis gene expression data to encourage their future reuse. DATA SOURCES: We searched National Institutes of Health Gene Expression Omnibus and EBI ArrayExpress for human gene expression microarray datasets. We also included the Glue Grant trauma gene expression cohorts. STUDY SELECTION: We selected clinical, time-matched, whole blood studies of sepsis and acute infections as compared to healthy and/or noninfectious inflammation patients. We identified 39 datasets composed of 3,241 samples from 2,604 patients. DATA EXTRACTION: All data were renormalized from raw data, when available, using consistent methods. DATA SYNTHESIS: Mean validation areas under the receiver operating characteristic curve for discriminating septic patients from patients with noninfectious inflammation for the Sepsis MetaScore, the FAIM3 to-PLAC8 ratio, and the Septicyte Lab were 0.82 (range, 0.73-0.89), 0.78 (range, 0.49-0.96), and 0.73 (range, 0.44-0.90), respectively. Paired-sample t tests of validation datasets showed no significant differences in area under the receiver operating characteristic curves. Mean validation area under the receiver operating characteristic curves for discriminating infected patients from healthy controls for the Sepsis MetaScore, FAIM3-to-PLAC8 ratio, and Septicyte Lab were 0.97 (range, 0.85-1.0), 0.94 (range, 0.65-1.0), and 0.71 (range, 0.24-1.0), respectively. There were few significant differences in any diagnostics due to pathogen type. CONCLUSIONS: The three diagnostics do not show significant differences in overall ability to distinguish noninfectious systemic inflammatory response syndrome from sepsis, though the performance in some datasets was low (area under the receiver operating characteristic curve, < 0.7) for the FAIM3-to PLAC8 ratio and Septicyte Lab. The Septicyte Lab also demonstrated significantly worse performance in discriminating infections as compared to healthy controls. Overall, public gene expression data are a useful tool for benchmarking gene expression diagnostics. PMID- 27681390 TI - " Karmanyevaddhikaraste Ma phalesukadachna Ma karma phalaheturbhur Ma teSangostvaakarmani" With deepest prayers to Goddess Saraswathi. PMID- 27681389 TI - Weighted-SAMGSR: combining significance analysis of microarray-gene set reduction algorithm with pathway topology-based weights to select relevant genes. AB - BACKGROUND: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method. METHODS: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to which this gene belongs. It ignores the topology information among pathways. In this study, we propose a weighted version of the SAMGSR algorithm by constructing weights based on the connectivity among genes and then combing these weights with the test statistics. RESULTS: Using both simulated and real-world data, we evaluate the performance of the proposed SAMGSR extension and demonstrate that the weighted version outperforms its original version. CONCLUSIONS: To conclude, the additional gene connectivity information does faciliatate feature selection. REVIEWERS: This article was reviewed by Drs. Limsoon Wong, Lev Klebanov, and, I. King Jordan. PMID- 27681391 TI - Diagnostic accuracy of direct digital radiography and conventional radiography for proximal caries detection in primary teeth: A systematic review. AB - OBJECTIVE: The present study was conducted to uncover the diagnostic accuracy of digital versus conventional radiographic methods for the detection of proximal caries in primary teeth. METHODS: Two researchers independently involved in the search process to explore Medical Subject Heading terms "dental digital radiography," "dental radiography," "bitewing," "dental caries," and "primary teeth" using PubMed, Cochrane Library, Ovid SP, and SIGLE databases. Search was confined to the articles published in English language only, with time period limit January 1996 to April 2014 and a hand search was performed to retrieve additional citations. Explicit inclusion and exclusion criteria were applied to eliminate undesired studies. Critical appraisal of the retrieved articles was done using the quality rating based on Bader and co-workers criteria. RESULTS: A total of 129 articles were retrieved, among which 4 articles were included. All the four studies included were in vitro, of which two studies attained a high quality score, whereas the other two attained average, and low scores based on Bader et al.'s criteria. CONCLUSIONS: A big lacuna exists in the literature, regarding the evaluation of radiographic systems in primary teeth, suggesting an immediate need for well conducted in vivo studies. The quality of available evidence can be regarded as fair but cannot be suggested to set a baseline, indicating a need to perform high-quality studies in a randomized sample to find out the accuracy of digital and conventional radiographs. PMID- 27681392 TI - A comparative evaluation of dental caries status among hearing-impaired and normal children of Malda, West Bengal, evaluated with the Caries Assessment Spectrum and Treatment. AB - CONTEXT: Dental caries is one of the major modern-day diseases of dental hard tissue. It may affect both normal and hearing-impaired children. AIMS: This study is aimed to evaluate and compare the prevalence of dental caries in hearing impaired and normal children of Malda, West Bengal, utilizing the Caries Assessment Spectrum and Treatment (CAST). SETTINGS AND DESIGN: In a cross sectional, case-control study of dental caries status of 6-12-year-old children was assessed. SUBJECTS AND METHODS: Statistically significant difference was found in studied (hearing-impaired) and control group (normal children). In the present study, caries affected hearing-impaired children found to be about 30.51% compared to 15.81% in normal children, and the result was statistically significant. Regarding individual caries assessment criteria, nearly all subgroups reflect statistically significant difference except sealed tooth structure group, internal caries-related discoloration in dentin, and distinct cavitation into dentine group, and the result is significant at P < 0.05. STATISTICAL ANALYSIS USED: Statistical analysis was carried out utilizing Z-test. RESULTS: Statistically significant difference was found in studied (hearing impaired) and control group (normal children). In the present study, caries effected hearing-impaired children found about 30.51% instead of 15.81% in normal children, and the result was statistically significant (P < 0.05). Regarding individual caries assessment criteria, nearly all subgroups reflect statistically significant difference except sealed tooth structure group, internal caries related discoloration in dentin, and distinct cavitation into dentine group. CONCLUSIONS: Dental health of hearing-impaired children was found unsatisfactory than normal children when studied in relation to dental caries status evaluated with CAST. PMID- 27681393 TI - Correlation of dental age, skeletal age, and chronological age among children aged 9-14 years: A retrospective study. AB - BACKGROUND: Growth can be one of the most uncertain variations, but understanding the same is very important for diagnosis and treatment planning. Skeletal age and dental age have been used to determine a child's developmental age. Several researchers have evaluated the association between dental and skeletal maturity with chronologic age on different population. The purpose of the present study was to find out whether dental age estimation can be replaced for skeletal age estimation in the Dakshina Kannada population. METHODS: A total of 104 samples equally distributed among both genders in the age group of 9-14 years were selected. Skeletal age was estimated using hand-wrist radiographs and Fishman's skeletal maturation index and dental age was measured using Demirjian's method. RESULTS: Spearman's rank-order correlation coefficients were used to measure the association between the skeletal maturity and dental maturity. The mean ages of male and female samples were determined as 11.89 +/- 1.867 years and 12.21 +/- 1.473 years, respectively. Chronological age was found to be positively correlated to dental age and skeletal age and found to be statistically significant (P < 0.01). The correlation between dental age and skeletal age was also found to be statistically significant with P < 0.001 and correlation coefficient of 0.683 and 0.704 for males and females. CONCLUSION: The present study showed a strong relation between the developmental ages in mixed dentition population; hence, dental age can be considered as a replacement in the study population. PMID- 27681394 TI - Comparative evaluation of antimicrobial efficacy of three different formulations of mouth rinses with multi-herbal mouth rinse. AB - CONTEXT: In response to the propagation of various anti-Streptococcus preventive agents, the discovery of newer and more efficient agents which are more economical, efficacious, and safe are gaining popularity in today's era. AIMS: The purpose was to compare the antimicrobial efficacy of multi-herbal mouth rinse with essential oil-based, fluoride containing, and 0.2% chlorhexidine digluconate mouth rinses, well-evidenced chemical formulations, against Streptococcus mutans. SETTINGS AND DESIGN: It is triple-blinded randomized controlled trial. METHODOLOGY: One hundred and twenty adolescents aged between 15 and 17 years were randomized into four groups: (a) multi-herbal mouth rinse, 15 ml twice a day; (b) 0.2% chlorhexidine mouth rinse, 15 ml twice a day; (c) essential oil mouth rinse, 15 ml twice a day (d) 0.2% sodium fluoride mouth rinse, twice a day. Salivary and plaque samples were collected from subjects and oral streptococci colony forming units (CFUs)/mL was assessed using TYCSB agar. STATISTICAL ANALYSIS USED: Repeated measures of ANOVA were used to compare the various mouthrinses followed by post hoc Bonferroni test for comparing multi-herbal mouthrinse with other mouthrinses. Significance was set at P < 0.05. RESULTS: At baseline, there was no statistically significant difference in the distribution of baseline data groups, but reduction of S. mutans colony count of multi-herbal mouth rinse in comparison with the other mouthrinses had statistically significant values except Fluoride mouth rinse till 1 week postrinsing. CONCLUSION: Chlorhexidine and multi-herbal mouth rinses showed statistically significant reduction in the S. mutans CFU count, in terms of efficacy and substantivity both. PMID- 27681395 TI - A comparative microleakage evaluation of three different base materials in Class I cavity in deciduous molars in sandwich technique using dye penetration and dentin surface interface by scanning electron microscope. AB - INTRODUCTION: A major objective in restorative dentistry is the control of marginal leakage, which may occur because of dimensional changes or lack of adaptation of restorative material to the cavity preparation. Numerous techniques have been advocated to overcome polymerization shrinkage in composite restorations. AIM AND OBJECTIVES: This study investigated microleakage of three different bases under composite resin in sandwich technique using dye penetration and dentin surface interface using scanning electron microscope (SEM). MATERIALS AND METHODS: Sixty extracted deciduous molars were stored in distilled water and Class I cavities with a width of about one-fourth of intercuspal distance and a depth of 0.5-1 mm below the dentino-enamel junction was prepared without bevels. In Group 1 - glass ionomer cement (GIC); Group 2 - mineral trioxide aggregate (MTA); Group 3 - BiodentineTM was placed as a base under composite. Teeth were longitudinally sectioned in two halves, through the centers of the restoration, immersed in 2% methylene blue and microleakage was evaluated under stereomicroscope and surface interface between base and dentin was evaluated under SEM. RESULTS: Under the condition of in vitro study, less microleakage and less internal gaps were seen in BiodentineTM (0.00 +/- 0.00 and 4.00 +/- 1.59) group than MTA (0.00 +/- 0.00 and 6.08 +/- 1.82) and GIC (25.25 +/- 6.57 and 14.73 +/- 3.72, respectively) and showed very strong positive correlation between microleakage and internal gaps. CONCLUSION: BiodentineTM exhibits superior marginal sealing ability as well as marginal adaptation under composite resin as compared to MTA and GIC. PMID- 27681396 TI - The effectiveness of pendulum, K-loop, and distal jet distalization techniques in growing children and its effects on anchor unit: A comparative study. AB - BACKGROUND: A common strategy to correct Class II malocclusions using a nonextraction protocol in children is to move the maxillary molars distally using molar distalization appliances, which usually derive their anchorage from maxillary premolars, causing mesialization of premolars and protrusion of incisors. OBJECTIVES: To evaluate the skeletal, dental and soft tissue changes produced by three different distalizing appliances, namely, pendulum, K-loop, and distal jet appliances. MATERIALS AND METHODS: Sixty-six children of mean age 14.13 years requiring molar distalization were divided into three groups: Group I (pendulum appliance), Group II (K-loop), and Group III (distal jet). Lateral cephalometric films were taken before and after 5 months of molar distalization and following cephalometric parameters were used to assess the effects of maxillary molar distalization, namely, anteroposterior skeletal (SNA/SNB/ANB), vertical skeletal (face height ratio/Frankfort-mandibular plane [FMA]/angle formed between Maxillary plane & Mandibular plane (MM)), interdental (overjet/overbite), maxillary dentoalveolar, and soft tissue parameters. RESULTS: There was no significant age difference between the three groups. In overall treatment changes among the three groups, the Anteroposterior skeletal changes were not statistically significant, vertically FMA angle increased by 1.79 degrees +/- 2.25 degrees and overbite reduced by 2.38 +/- 1.83 mm. The maxillary first molars were distalized by an average of 4.70 +/- 3.01 mm (Upper 6 [U6] to pterygoid vertical [PTV]). The maxillary central incisor labial tipping increased to an average of 1.61 +/- 2.73 mm and cant of upper lip increased by 3.40 degrees +/- 5.88 degrees are statistically significant (P < 0.05). CONCLUSION: All three distalization techniques in growing children produced significant effects on anchor unit. There was an increase in FMA angle, significant bite opening, proclination of the maxillary incisors and increase in the cant of the upper lip. PMID- 27681397 TI - Salivary IgA and dental caries in HIV patients: A pilot study. AB - INTRODUCTION: The interrelationship of human immunodeficiency virus (HIV) infection and dental caries, as well as Salivary IgA (S-IgA) level, appear to remain underexplored while a manual and electronic search of the literature was made. Hence, this study was undertaken to assess the relationship of S-IgA and dental caries status in HIV +ve children. AIM: The aim of this study was to find out the relationship of S-IgA antibody with dental caries by measuring the concentration of IgA in saliva of HIV +ve and HIV -ve children and to determine the dental caries status in HIV +ve and HIV -ve children, which may help in treatment planning and prevention of the same. MATERIALS AND METHODS: Twenty eight HIV +ve children aged between 6 and 14 years and 28 age matched HIV -ve children were included in this study, and both samples were randomly selected from the same nongovernmental organization (NGO). The HIV status of both these samples was confirmed from their medical records provided by the NGO. 2 cc of unstimulated saliva was collected from both groups in special tubes coded numerically using the method described by Collins and Dawes, and the samples were analyzed to measure the concentration of IgA using commercially available ELISA kit (DRG Diagnostics, Germany). Examination of dental caries was carried out according to the WHO criteria (1997) using a flat mouth mirror and Community periodontal index (CPI) probe. RESULTS: In HIV +ve group, mean salivary IgA level was calculated as 81.61 +/- 6.20 MUg/ml, mean decayed, missing, filled teeth (DMFT) was 3.86 +/- 3.37, mean decayed, extracted and filled teeth (deft) was 4.75 +/- 2.86. In HIV -ve group, the mean salivary IgA level was calculated as 145.57 +/-17.83 MUg/ml, mean DMFT was 2.54 +/- 0.69, mean deft was 2.43 +/- 2.01. Strong -ve correlation between S-IgA and DMFT (r = -0.781, t = 6.38, P < 0.001) and negative, but not significant correlation (r = -0.19, t = 0.99, P > 0.05) between S-IgA and deft was found in HIV +ve group. Strong -ve correlation between S-IgA and DMFT (r = -0.655, t = 4.42, P < 0.001), S-IgA and deft (r = -0.942, t = 14.32, P < 0.001) was found in HIV -ve group. CONCLUSION: This study suggests that the individuals, who are suffering from IgA deficiency in general, are more susceptible to dental caries than normal individuals. PMID- 27681398 TI - Dental students' compliance with antibiotic prescribing guidelines for dental infections in children. AB - CONTEXT: To investigate the antibiotic prescribing training received by dental students, clinical experience in treating child patients, awareness of antibiotic prescribing guidelines, preparedness in antibiotic prescribing, and compliance with antibiotic prescribing guidelines for the management of dental infections in children. METHODS: This was a cross-sectional study involving final year dentals students from Malaysian and Asian dental schools. A self-administered questionnaire consisting of five clinical case scenarios was e-mailed to all final year students at selected dental schools. Students' responses were compared for each clinical case scenario with the prescribing guidelines of the American Academy of Pediatric Dentistry and the American Dental Association. Compliance in each scenario was tested for association with their preparedness in antibiotic prescribing, previous training on antibiotic prescribing and awareness of antibiotic prescribing guidelines using Chi-square test. Data collected were analyzed using SPSS statistics version 20. RESULTS: A total of 108 completed responses were received. About 74 (69%) students were from Malaysian dental schools. The compliance rate with prescribing guidelines ranged from 15.7% to 43.5%. Those attending Malaysian dental schools (47.3%) and those who had treated child patient more often (46.3%) were more likely (P < 0.05) to be aware of the guidelines. Those who had received antibiotic prescribing training (21.3%) were more likely to think they were well prepared in antibiotic prescribing (P < 0.05). CONCLUSIONS: Final year dental students had low awareness and compliance with antibiotic prescribing guidelines. Further research is needed to investigate how compliance with the guidelines may be enhanced. PMID- 27681399 TI - Strength and difficulties questionnaire: A tool as prerequisite to measure child's mental health problems attending dental clinics. AB - INTRODUCTION: Child's behavior on dental visit depends on variables such as age, parental behavior, parental anxiety, medical/dental history, and dental procedures. Behavioral-screening questionnaire, such as the Strengths and Difficulties Questionnaire (SDQ), can be used to preassess the child's mental health status which further predicts child behavioral pattern in dental clinics. AIM: To measure emotional status among children of 3-14 years age group attending dental clinics. METHODOLOGY: A total of 176 parents of children aged 3-14 years were involved in this study. The child's emotional and behavioral statuses were assessed using SDQ. RESULTS: On analyzing the SDQ data, it was found that 80% of children came under the abnormal category whereas only 8% of children were found to be in normal category. Twelve percent of children came under borderline category. On the individual behavioral subsets scores, 13% were rated as abnormal on emotional subset, 40% on conduct problems, 12% on hyperactivity, and 29% on peer problems subset. CONCLUSION: Findings of this study suggest that incorporating tools to identify the current emotional state would give a clue and allow the dentist to develop a behavior guidance plan to accomplish the necessary oral health care. However, the results are preliminary; studies with larger sample should be done to validate the results among diverse populations. PMID- 27681400 TI - New fluoride MI Varnish as root canal sealer: An in vitro analysis of bacterial leakage. AB - AIMS: The aim of the present study was to evaluate and compare the sealing ability of root canal obturation after the application of fluoride varnish (MI Varnish) containing 5% sodium fluoride and casein phosphopeptide-amorphous calcium phosphate, fluoride varnish, and AH Plus and AH-Plus as root canal sealer by bacterial penetration test. MATERIALS AND METHODS: Root canals of 65 single rooted and single-canalled teeth were prepared. They were divided into three experimental groups (n = 15) and two control groups (n = 10). The root canal walls in Group I were coated with AH Plus, Group II were coated with AH Plus and fluoride varnish, and Group III were coated with fluoride varnish. All the teeth were obturated with gutta-percha using the lateral condensation technique. Enterococcus faecalis were used as test bacteria to determine the leakage during 100 days. STATISTICAL ANALYSIS: The data were analyzed using log-rank test and Kaplan-Meier survival analysis. RESULTS: Group III showed significantly less bacterial penetration as compared to Group I (P = 0.01) and Group II (P = 0.03). However, there was no statistical significance between Groups I and II (P = 0.672). CONCLUSIONS: It can be concluded from the present study that fluoride varnish can be used as a root canal sealer. However, further in vitro and in vivo studies are required. PMID- 27681401 TI - Dental neglect among children in Chennai. AB - BACKGROUND: Child dental neglect is the failure of a parent or guardian to meet the child's basic oral health needs such that the child enjoys adequate function and freedom from pain and infection, where reasonable resources are available to family or caregiver. AIM: The aim of the study is to evaluate the phenomenon of dental neglect among children in Chennai and to associate dental neglect with oral health status of children aged 3-12 years. MATERIALS AND METHODS: This is a cross-sectional study involving 478 pairs of parents and children. Dental neglect scale and a questionnaire were used to assess the dental neglect score among parents of the children involved in the study. Oral health status of children was clinically assessed using oral hygiene index, decayed, extracted, filled teeth (def(t)), pulp, ulcers, fistula, abscess (pufa), decayed, missing, filled teeth (DMFT), PUFA as per the World Health Organization criteria and pufa/PUFA index. Student's t-test and one-way ANOVA were used appropriately for statistical analysis using SPSS software version 20.0. RESULTS: A significant higher dental neglect score was reported among the parents who reside in the suburban location (P < 0.001), whose educational qualification was secondary (P < 0.001) and who have not availed any dental service for >3 years (P = 0.001). A significant higher DMFT (P = 0.003), deft (P = 0 < 0.001), pufa (P = 0.011), and debris index (P = 0.002) scores were seen in the higher dental neglect group. CONCLUSION: Child dental neglect is seen among the parents whose educational qualification was secondary, who reside in the suburban location, and who have not utilized the dental services for more than 3 years in Chennai. This dental neglect results in poorer oral health of children. PMID- 27681402 TI - Cariogenic microbiota of children under chemotherapy: A pilot study. AB - AIM: To analyze the cariogenic microbiota of children who are under antineoplastic therapy. METHODS: Twenty-seven patients undergoing cancer treatment in the Pediatric Unit of Mato Grosso Cancer Hospital were selected. The inclusion criteria of volunteers were being under chemotherapy in the saliva collection period, age between 2 and 18 years, collaborate with the protocol for clinical examination and saliva collection, and responsible have given their written consent. For the realization of lactobacilli and Streptococcus mutans count in the patients' saliva, respectively, Dentalcult I and II (LaborClin; ) kits were used. STATISTICAL ANALYSIS: Kruskal-Wallis and Fisher's exact tests were used to assess the association of the variables age group, prevalence of lactobacilli and S. mutans, diagnosis of patients, presence and level of decay of patients defined by decayed, filled, and missing teeth (DMFT)/dmft indexes with a significance level of 5%. RESULTS: The group of patients consisted of 27 children, 15 males, and 12 females; 44% were aged between 6 and 10 years; 61% had present or past history of caries (dmft/DMFT >0); 48% had low value for Dentalcult I; 59% presented value grade 0 to Dentalcult II; and 63% were diagnosed with acute lymphoid leukemia. CONCLUSION: There was a high prevalence of dental caries in the study population but low rates of S. mutans and lactobacilli in the saliva of the children. Lactobacilli rate was significantly associated with caries index scores, and the prevalence of caries was directly associated with the age group of the children. PMID- 27681403 TI - Comparison of fracture resistance of simulated immature teeth with an open apex using Biodentine and composite resin: An in vitro study. AB - AIM: To evaluate the fracture resistance in simulated immature teeth that had been backfilled using composite resin and Biodentine after using Biodentine as an apical plug material immediately and after 3 months of aging. MATERIALS AND METHODS: Sixty extracted human maxillary central incisors were simulated in an immature open apex. The roots of all the specimens were then standardized to a length of 10 mm and canals were instrumented to obtain the radicular dentin thickness around 1.5 mm. All the specimens were then randomly divided into three groups of twenty teeth each. Group I (control) - 4 mm apical plug of Biodentine backfilled with thermoplasticized gutta-percha. Group II - 4 mm apical plug of Biodentine and then backfilled with ParaCore. Group III - completely filled with Biodentine. Ten samples from each group were randomly divided into two subgroups. In subgroup A: Specimens were stored for 1 week. In subgroup B: Specimens were stored in phosphate-buffered saline solution for 3 months and were subjected to universal testing machine. Statistical analysis was done using one-way analysis. RESULTS: No significant difference in fracture resistance between the groups was observed when tested immediately. After 3 months of aging, only Biodentine group showed a significant reduction in fracture resistance without significant reduction with other two groups. CONCLUSION: Biodentine group has shown a drastic reduction in fracture resistance after 3 months of aging, and hence cannot be recommended as a reinforcement material in immature teeth with thin dentin walls. PMID- 27681405 TI - Effect of newer antioxidants on the bond strength of composite on bleached enamel. AB - AIM: The study aims to evaluate the effect of the application of two antioxidants on the bond strength of composite resin to bleached enamel. MATERIALS AND METHODS: Eighty enamel surfaces were obtained from forty human extracted premolars. Specimens were randomly divided into four groups (n = 20). Group 1: No bleaching (control); Group 2a: Bleaching with 15% carbamide peroxide gel; Group 2b: Bleaching, followed by application of 10% sodium ascorbate gel; Group 2c: Bleaching, followed by application of 5% proanthocyanidin agent. Surfaces were etched followed by application of total etch bonding system, and composite resin cylinders were bonded. Specimens were tested for shear bond strength. STATISTICAL ANALYSIS USED: One-way analysis of variance was used for multiple group comparison and post hoc Tukey's test for individual group-wise comparison. RESULTS: Significantly higher shear bond strength values were observed in Group 2c and 2b as compared with Group 1 and 2a (P < 0.05). Among the antioxidants, Group 2c showed significantly higher shear bond strength values than Group 2b (P < 0.05). CONCLUSION: It can be concluded that the use of antioxidant before bonding procedures on bleached enamel completely neutralizes the deleterious effects of bleaching and increases the bond strength significantly. PMID- 27681404 TI - Single- versus two-visit pulpectomy treatment in primary teeth with apical periodontitis: A double-blind, parallel group, randomized controlled trial. AB - CONTEXT: Reduction of the bacterial populations to levels compatible with periradicular tissue healing is the primary microbiological goal of the endodontic treatment of teeth with apical periodontitis. The number of visits required to treat teeth with apical periodontitis represents one of the most debatable issues in endodontics. OBJECTIVES: The objective of this study was to compare and evaluate the clinical and radiographic outcome of single- versus two visit pulpectomy treatment in primary teeth with apical periodontitis at the end of 6-month healing period. SETTINGS AND DESIGN: A parallel group, double-blind, randomized controlled trial was carried out in 64 children aged 4-8 years. Nonvital primary teeth with apical periodontitis with enough coronal structure were selected. Sixty-four children were assigned randomly into two groups (32 children each) by block randomization, and allocation concealment was done with closed envelop method. METHODS AND MATERIALS: Group I underwent single-visit pulpectomy followed by obturation with zinc oxide eugenol (ZOE). Group II underwent conventional two-visit pulpectomy with intracanal calcium hydroxide, followed by obturation with ZOE. Postoperative clinical and radiographic evaluation was carried out at 1, 3, and 6 months after the end of the treatment. STATISTICAL ANALYSIS USED: The data were analyzed by Wilcoxon's signed rank test, Mann-Whitney U-test, and Friedman test. RESULTS: There was no statistically significant difference in clinical and radiographic outcomes in both the groups at the end of 6-month healing period. CONCLUSION: Single-visit pulpectomy can be considered as a viable option for the treatment of primary teeth with apical periodontitis. PMID- 27681406 TI - C-shaped mandibular primary first molar diagnosed with cone beam computed tomography: A novel case report and literature review of primary molars' root canal systems. AB - Knowledge of the different anatomical variations in root canal system of dedicious dentition will improve the practice of the pediatric dentists. The teeth with C-shaped root canal configurations are definitely a problem in endodontic treatment. Dentists who are specialists of endodontics must have adequate knowledge about various root canal morphologies of primary tooth that have a tendency for rapid progression of dental caries to achieve a technically satisfactory outcome. This report presents an extraordinary case of unusual tooth morphology involving the mandibular first primary molar with a C-shaped configuration which has not yet been reported. PMID- 27681407 TI - Postconcussion symptoms reported by Operation Enduring Freedom/Operation Iraqi Freedom veterans with and without blast exposure, mild traumatic brain injury, and posttraumatic stress disorder. AB - OBJECTIVE: This study examined symptom reporting related to the 10th Edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria for postconcussional syndrome (PCS) in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) Veterans. Our aims were to: (a) examine relationships among PCS symptoms by identifying potential subscales of the British Columbia Postconcussion Symptom Inventory (BC-PSI); and (b) examine group differences in BC-PSI items and subscales in Veterans with and without blast exposure, mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD). METHOD: Our sample included Veterans with blast-related mTBI history (n = 47), with blast exposure but no mTBI history (n = 20), and without blast exposure (n = 23). Overall, 37 Veterans had PTSD, and 53 did not. We conducted an exploratory factor analysis (EFA) of the BC-PSI followed by multivariate analysis of variance to examine differences in BC-PSI subscale scores by blast exposure, mTBI history, and PTSD. RESULTS: BC-PSI factors were interpreted as cognitive, vestibular, affective, anger, and somatic. Items and factor scores were highest for Veterans with blast exposure plus mTBI, and lowest for controls. Vestibular, affective, and somatic factors were significantly higher for Veterans with blast exposure plus mTBI than for controls, but not significantly different for those with blast exposure but no mTBI. These results remained significant when PTSD symptom severity was included as a covariate. Cognitive, anger, and somatic subscales were significantly higher for Veterans with PTSD, though there was no interaction effect of PTSD and mTBI or blast history. CONCLUSIONS: EFA-derived subscales of the BC-PSI differentiated Veterans based on blast exposure, mTBI history, and PTSD. PMID- 27681409 TI - Implicit Theories, Expectancies, and Values Predict Mathematics Motivation and Behavior across High School and College. AB - Mathematics motivation declines for many adolescents, which limits future educational and career options. The present study sought to identify predictors of this decline by examining whether implicit theories assessed in ninth grade (incremental/entity) predicted course-taking behaviors and utility value in college. The study integrated implicit theory with variables from expectancy value theory to examine potential moderators and mediators of the association of implicit theories with college mathematics outcomes. Implicit theories and expectancy-value variables were assessed in 165 American high school students (47 % female; 92 % White), who were then followed into their college years, at which time mathematics courses taken, course-taking intentions, and utility value were assessed. Implicit theories predicted course-taking intentions and utility value, but only self-concept of ability predicted courses taken, course-taking intentions, and utility value after controlling for prior mathematics achievement and baseline values. Expectancy for success in mathematics mediated associations between self-concept of ability and college outcomes. This research identifies self-concept of ability as a stronger predictor than implicit theories of mathematics motivation and behavior across several years: math self-concept is critical to sustained engagement in mathematics. PMID- 27681408 TI - Childhood Adversity and Early Initiation of Alcohol Use in Two Representative Samples of Puerto Rican Youth. AB - Early alcohol use is associated with multiple negative outcomes later in life, including substance use disorders. Identification of factors related to this very early risk indicator can help inform early prevention efforts. This study prospectively examined the relationship between childhood adversities and early initiation of alcohol use (by age 14) among Puerto Rican youth, the Latino subgroup at highest risk for alcohol use disorders in adulthood. The data come from the Boricua Youth Study, a longitudinal study of Puerto Rican youth in two sites (South Bronx, New York, and the standard metropolitan area of San Juan, Puerto Rico). We focus on youth who were ages 10 and older at Wave 1 [M age at Wave 1 (SE) = 11.64(0.05), N = 1259, 48.85 % females]. Twelve childhood adversities were measured at Wave 1 and include 10 adverse childhood experiences commonly studied and two additional ones (exposure to violence and discrimination) that were deemed relevant for this study's population. Early initiation of alcohol use was determined based on youth report at Waves 1 through 3 (each wave 1 year apart). Cox proportional hazards models showed that, when considered individually, adversities reflecting child maltreatment, parental maladjustment, and sociocultural stressors were related to early initiation of alcohol use. Significant gender interactions were identified for parental emotional problems and exposure to violence, with associations found among girls only. Adversities often co-occurred, and when they were considered jointly, physical and emotional abuse, parental antisocial personality, and exposure to violence had independent associations with early alcohol use, with a stronger influence of exposure to violence in girls compared to boys. The accumulation of adversities, regardless of the specific type of exposure, increased the risk for starting to drink at a young age in a linear way. The associations between childhood adversities and early alcohol use were generally consistent across sociocultural contexts, in spite of differences in the prevalence of exposure to adversity. Our findings highlight the importance of targeting multiple adversities and expanding the notion of adversity to capture the experiences of specific groups more adequately. PMID- 27681410 TI - Longitudinal Relations between Beliefs Supporting Aggression,Anger Regulation, and Dating Aggression among Early Adolescents. AB - Dating aggression occurs frequently in early to mid-adolescence and has negative repercussions for psychosocial adjustment and physical health. The patterns of behavior learned during this developmental timeframe may persist in future dating relationships, underscoring the need to identify risk factors for this outcome. The current study examined longitudinal relations between beliefs supporting aggression, anger regulation, and dating aggression. Participants were 176 middle school students in sixth, seventh, and eighth grade (50 % female; 82 % African American). No direct effects were found between beliefs supporting reactive or proactive aggression and dating aggression. Beliefs supporting reactive aggression predicted increased rates of anger dysregulation, and beliefs supporting proactive aggression led to subsequent increases in anger inhibition. Anger dysregulation and inhibition were associated with higher frequencies of dating aggression. An indirect effect was found for the relation between beliefs supporting reactive aggression and dating aggression via anger dysregulation. Another indirect effect emerged for the relation between beliefs supporting proactive aggression and dating aggression through anger inhibition. The study's findings suggested that beliefs supporting proactive and reactive aggression were differentially related to emotion regulation processes, and identified anger dysregulation and inhibition as risk factors for dating aggression among adolescents. PMID- 27681411 TI - P21 (Cdc42/Rac)-activated kinase 1 (pak1) is associated with cardiotoxicity induced by antihistamines. AB - Astemizole, a non-sedating histamine H1 receptor blocker, is widely known to cause cardiac arrhythmia, which prolongs the QT interval. However, the precise molecular mechanism involved in antihistamine-induced cardiovascular adverse effects other than hERG channel inhibition is still unclear. In this study, we used DNA microarray analysis to detect the mechanisms involved in life threatening adverse effects caused by astemizole. Rat primary cardiomyocytes were treated with various concentrations of astemizole for 24 h and the corresponding cell lysates were analyzed using a DNA microarray. Astemizole altered the expression profiles of genes involved in calcium transport/signaling. Using qRT PCR analysis, we demonstrated that, among those genes, p21 (Cdc42/Rac)-activated kinase 1 (pak1) mRNA was downregulated by treatment with terfenadine and astemizole. Astemizole also reduced pak1 protein levels in rat cardiomyocytes. In addition, astemizole decreased pak1 mRNA and protein levels in H9c2 cells and induced an increase in cell surface area (hypertrophy) and cytotoxicity. Fingolimod hydrochloride (FTY720), a pak1 activator, inhibited astemizole-induced hypertrophy and cytotoxicity in H9c2 cells. These results suggest that antihistamine-induced cardiac adverse effects are associated with pak1 expression and function. PMID- 27681412 TI - Phylogenetic relationships of D. rudis (Bedriaga, 1886) and D. bithynica(Mehely, 1909) based on microsatellite and mitochondrial DNA in Turkey. AB - The spiny-tailed lizard of the genus Darevskia have a series of taxonomic revisions, but still their phylogenetic relationships remain uncertain. In the present study, we have assessed taxonomic relationships among Darevskia bithynica and Darevskia rudis populations through estimation of phylogenetic relationships among 96 specimens using microsatellite DNA (Du215, Du281, Du323 and Du418 loci) and 53 specimens using mtDNA (16S rRNA and cytb) from main populations in Turkey. Although D. b. bithynica and D. r. mirabilis were separated based on the PCoA analysis at low level from other D. rudis and D. bithynica populations, the distance values of Nei's genetic distance, Nei's unbiased genetic distance, Fst and Linear Fst were not high among taxa in microsatellite DNA. On the other hand, our phylogenetic analyses (NJ, ML, MP and BI) did not separate D. rudis and D. bithynica populations. Finally, most of the topologically identical trees of phylogenetic analyses and microsatellite results showed that the extant populations of D. rudis and D. bithynica were found to be polytomy. Based on our molecular phylogenetic study, D. rudis complex is still ongoing revisions. PMID- 27681413 TI - Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect? AB - BACKGROUND: Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto's thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC. METHODS: Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN gamma ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis. RESULTS: PTC with LT cases showed significantly higher expression of TNF-alpha (p = .043), IFN-gamma (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker. CONCLUSIONS: These results indicate that mixed Th1 (TNF-alpha, IFN-gamma , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis. PMID- 27681414 TI - Depersonalization and derealization in self-report and clinical interview: The spectrum of borderline personality disorder, dissociative disorders, and healthy controls. AB - Depersonalization (DEP) and derealization (DER) were examined among college students with and without borderline personality disorder (BPD) and/or dissociative disorders (DDs) by self-report and clinician assessment. The Steinberg Depersonalization Questionnaire (SDEPQ), the Steinberg Derealization Questionnaire (SDERQ), the Childhood Trauma Questionnaire, and the screening tool of the BPD section of the Structured Clinical Interview for DSM-IV (SCID-BPD) were administered to 1,301 students. Those with BPD (n = 80) according to the SCID-BPD and 111 non-BPD controls were evaluated using the Structured Clinical Interview for DSM-IV Dissociative Disorders by a psychiatrist blind to the diagnosis. Of the participants, 19.7% reported SDEPQ (17.8%) and/or SDERQ (11.0%) scores above cutoff levels and impairment from these experiences. Principal component analysis of 26 items of both scales yielded 4 factors: cognitive emotional self-detachment, perceptual detachment, bodily self-detachment, and detachment from reality. Participants with concurrent DD and BPD had the highest scores for DEP and DER in the clinical interview and self-report. The total number of BPD criteria was associated with the severity of childhood trauma and dissociation. Both BPD and DD were associated with clinician-assessed and self reported DER, self-reported DEP, and the cognitive-emotional self-detachment factor. Unlike BPD, DD was associated with clinician-assessed DEP, and BPD was related to the self-reported detachment from reality factor. Although the latter was correlated with the total childhood trauma score, possibly because of dissociative amnesia, clinician-assessed DER was not. Being the closest factor to BPD, the factor of detachment from reality warrants further study. PMID- 27681415 TI - Dynamic Regulation of a Ribosome Rescue Pathway in Erythroid Cells and Platelets. AB - Protein synthesis continues in platelets and maturing reticulocytes, although these blood cells lack nuclei and do not make new mRNA or ribosomes. Here, we analyze translation in primary human cells from anucleate lineages by ribosome profiling and uncover a dramatic accumulation of post-termination unrecycled ribosomes in the 3' UTRs of mRNAs. We demonstrate that these ribosomes accumulate as a result of the natural loss of the ribosome recycling factor ABCE1 during terminal differentiation. Induction of the ribosome rescue factors PELO and HBS1L is required to support protein synthesis when ABCE1 levels fall and for hemoglobin production during blood cell development. Our observations suggest that this distinctive loss of ABCE1 in anucleate blood lineages could sensitize them to defects in ribosome homeostasis, perhaps explaining in part why genetic defects in the fundamental process of ribosome production ("ribosomopathies") often affect hematopoiesis specifically. PMID- 27681417 TI - Super-Enhancers at the Nanog Locus Differentially Regulate Neighboring Pluripotency-Associated Genes. AB - Super-enhancers are tissue-specific cis-regulatory elements that drive expression of genes associated with cell identity and malignancy. A cardinal feature of super-enhancers is that they are transcribed to produce enhancer-derived RNAs (eRNAs). It remains unclear whether super-enhancers robustly activate genes in situ and whether their functions are attributable to eRNAs or the DNA element. CRISPR/Cas9 was used to systematically delete three discrete super-enhancers at the Nanog locus in embryonic stem cells, revealing functional differences in Nanog transcriptional regulation. One distal super-enhancer 45 kb upstream of Nanog (-45 enhancer) regulates both nearest neighbor genes, Nanog and Dppa3. Interestingly, eRNAs produced at the -45 enhancer specifically regulate Dppa3 expression by stabilizing looping of the -45 enhancer and Dppa3. Our work illustrates that genomic editing is required to determine enhancer function and points to a method to selectively target a subset of super-enhancer-regulated genes by depleting eRNAs. PMID- 27681418 TI - mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. AB - FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance. Rather, mTORC1 mediated many of the beneficial actions of FGF21 in vitro, including UCP1 and FGF21 induction, increased adiponectin secretion, and enhanced glucose uptake without any adverse effects on insulin action. This study provides a global view of FGF21 signaling and suggests that mTORC1 may act to facilitate FGF21-mediated health benefits in vivo. PMID- 27681416 TI - Uniformity of Peptide Release Is Maintained by Methylation of Release Factors. AB - Termination of protein synthesis on the ribosome is catalyzed by release factors (RFs), which share a conserved glycine-glycine-glutamine (GGQ) motif. The glutamine residue is methylated in vivo, but a mechanistic understanding of its contribution to hydrolysis is lacking. Here, we show that the modification, apart from increasing the overall rate of termination on all dipeptides, substantially increases the rate of peptide release on a subset of amino acids. In the presence of unmethylated RFs, we measure rates of hydrolysis that are exceptionally slow on proline and glycine residues and approximately two orders of magnitude faster in the presence of the methylated factors. Structures of 70S ribosomes bound to methylated RF1 and RF2 reveal that the glutamine side-chain methylation packs against 23S rRNA nucleotide 2451, stabilizing the GGQ motif and placing the side chain amide of the glutamine toward tRNA. These data provide a framework for understanding how release factor modifications impact termination. PMID- 27681420 TI - Discovery and Function of a General Core Hormetic Stress Response in E. coli Induced by Sublethal Concentrations of Antibiotics. AB - A better understanding of the impact of antibiotics on bacteria is required to increase the efficiency of antibiotic treatments and to slow the emergence of resistance. Using Escherichia coli, we examined how bacteria exposed to sublethal concentrations of ampicillin adjust gene expression patterns and metabolism to simultaneously deal with the antibiotic-induced damage and maintain rapid growth. We found that the treated cells increased energy production, as well as translation and macromolecular repair and protection. These responses are adaptive, because they confer increased survival not only to lethal ampicillin treatment but also to non-antibiotic lethal stresses. This robustness is modulated by nutrient availability. Because different antibiotics and other stressors induce the same set of responses, we propose that it constitutes a general core hormetic stress response. It is plausible that this response plays an important role in the robustness of bacteria exposed to antibiotic treatments and constant environmental fluctuations in natural environments. PMID- 27681419 TI - MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset. AB - Seizures are bursts of excessive synchronized neuronal activity, suggesting that mechanisms controlling brain excitability are compromised. The voltage-gated potassium channel Kv4.2, a major mediator of hyperpolarizing A-type currents in the brain, is a crucial regulator of neuronal excitability. Kv4.2 expression levels are reduced following seizures and in epilepsy, but the underlying mechanisms remain unclear. Here, we report that Kv4.2 mRNA is recruited to the RNA-induced silencing complex shortly after status epilepticus in mice and after kainic acid treatment of hippocampal neurons, coincident with reduction of Kv4.2 protein. We show that the microRNA miR-324-5p inhibits Kv4.2 protein expression and that antagonizing miR-324-5p is neuroprotective and seizure suppressive. MiR 324-5p inhibition also blocks kainic-acid-induced reduction of Kv4.2 protein in vitro and in vivo and delays kainic-acid-induced seizure onset in wild-type but not in Kcnd2 knockout mice. These results reveal an important role for miR-324-5p mediated silencing of Kv4.2 in seizure onset. PMID- 27681421 TI - Adaptation without Plasticity. AB - Sensory adaptation is a phenomenon in which neurons are affected not only by their immediate input but also by the sequence of preceding inputs. In visual cortex, for example, neurons shift their preferred orientation after exposure to an oriented stimulus. This adaptation is traditionally attributed to plasticity. We show that a recurrent network generates tuning curve shifts observed in cat and macaque visual cortex, even when all synaptic weights and intrinsic properties in the model are fixed. This demonstrates that, in a recurrent network, adaptation on timescales of hundreds of milliseconds does not require plasticity. Given the ubiquity of recurrent connections, this phenomenon likely contributes to responses observed across cortex and shows that plasticity cannot be inferred solely from changes in tuning on these timescales. More broadly, our findings show that recurrent connections can endow a network with a powerful mechanism to store and integrate recent contextual information. PMID- 27681422 TI - NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In Mice. AB - Photoreceptor death is the endpoint of many blinding diseases. Identifying unifying pathogenic mechanisms in these diseases may offer global approaches for facilitating photoreceptor survival. We found that rod or cone photoreceptor specific deletion of nicotinamide phosphoribosyltransferase (Nampt), the rate limiting enzyme in the major NAD(+) biosynthetic pathway beginning with nicotinamide, caused retinal degeneration. In both cases, we could rescue vision with nicotinamide mononucleotide (NMN). Significantly, retinal NAD(+) deficiency was an early feature of multiple mouse models of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age associated dysfunction. Mechanistically, NAD(+) deficiency caused metabolic dysfunction and consequent photoreceptor death. We further demonstrate that the NAD(+)-dependent mitochondrial deacylases SIRT3 and SIRT5 play important roles in retinal homeostasis and that NAD(+) deficiency causes SIRT3 dysfunction. These findings demonstrate that NAD(+) biosynthesis is essential for vision, provide a foundation for future work to further clarify the mechanisms involved, and identify a unifying therapeutic target for diverse blinding diseases. PMID- 27681423 TI - Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3. AB - Synaptic receptors gate the neuronal response to incoming signals, but they are not homogeneously distributed on dendrites. A spatially defined receptor distribution can preferentially amplify certain synaptic inputs, resize receptive fields of neurons, and optimize information processing within a neuronal circuit. Thus, a longstanding question is how the spatial organization of synaptic receptors is achieved. Here, we find that action potentials provide local signals that influence the distribution of synaptic AMPA receptors along dendrites in mouse cerebellar stellate cells. Graded dendritic depolarizations elevate CPEB3 protein at proximal dendrites, where we suggest that CPEB3 binds to GluA2 mRNA, suppressing GluA2 protein synthesis leading to a distance-dependent increase in synaptic GluA2 AMPARs. The activity-induced expression of CPEB3 requires increased Ca(2+) and PKC activation. Our results suggest a cell-autonomous mechanism where sustained postsynaptic firing drives graded local protein synthesis, thus directing the spatial organization of synaptic AMPARs. PMID- 27681424 TI - PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons. AB - The fidelity of RNA splicing is maintained by a network of factors, but the molecular mechanisms that govern this process have yet to be fully elucidated. We previously found that TDP-43, an RNA-binding protein implicated in neurodegenerative disease, utilizes UG microsatellites to repress nonconserved cryptic exons and prevent their incorporation into mRNA. Here, we report that two well-characterized splicing factors, polypyrimidine tract-binding protein 1 (PTBP1) and polypyrimidine tract-binding protein 2 (PTBP2), are also nonconserved cryptic exon repressors. In contrast to TDP-43, PTBP1 and PTBP2 utilize CU microsatellites to repress both conserved tissue-specific exons and nonconserved cryptic exons. Analysis of these conserved splicing events suggests that PTBP1 and PTBP2 repression is titrated to generate the transcriptome diversity required for neuronal differentiation. We establish that PTBP1 and PTBP2 are members of a family of cryptic exon repressors. PMID- 27681425 TI - Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing. AB - Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by ten genes that comprise the glucuronidation pathway. Deep RNA sequencing of major metabolic organs exposes a substantial expansion of the UGT transcriptome by alternative splicing, with variants representing 20% to 60% of canonical transcript expression. Nearly a fifth of expressed variants comprise in-frame sequences that may create distinct structural and functional features. Follow-up cell-based assays reveal biological functions for these alternative UGT proteins. Some isoforms were found to inhibit or induce inactivation of drugs and steroids in addition to perturbing global cell metabolism (energy, amino acids, nucleotides), cell adhesion, and proliferation. This work highlights the biological relevance of alternative UGT expression, which we propose increases protein diversity through the evolution of metabolic regulators from specific enzymes. PMID- 27681426 TI - Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing. AB - Spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations. PMID- 27681427 TI - Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin Producing Cells. AB - Dietary leucine has been suspected to play an important role in insulin release, a hormone that controls satiety and metabolism. The mechanism by which insulin producing cells (IPCs) sense leucine and regulate insulin secretion is still poorly understood. In Drosophila, insulin-like peptides (DILP2 and DILP5) are produced by brain IPCs and are released in the hemolymph after leucine ingestion. Using Ca(2+)-imaging and ex vivo cultured larval brains, we demonstrate that IPCs can directly sense extracellular leucine levels via minidiscs (MND), a leucine transporter. MND knockdown in IPCs abolished leucine-dependent changes, including loss of DILP2 and DILP5 in IPC bodies, consistent with the idea that MND is necessary for leucine-dependent DILP release. This, in turn, leads to a strong increase in hemolymph sugar levels and reduced growth. GDH knockdown in IPCs also reduced leucine-dependent DILP release, suggesting that nutrient sensing is coupled to the glutamate dehydrogenase pathway. PMID- 27681428 TI - The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment. AB - The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor-RHOX10-critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general. PMID- 27681429 TI - Wnt Regulates Proliferation and Neurogenic Potential of Muller Glial Cells via a Lin28/let-7 miRNA-Dependent Pathway in Adult Mammalian Retinas. AB - In cold-blooded vertebrates such as zebrafish, Muller glial cells (MGs) readily proliferate to replenish lost retinal neurons. In mammals, however, MGs lack regenerative capability as they do not spontaneously re-enter the cell cycle unless the retina is injured. Here, we show that gene transfer of beta-catenin in adult mouse retinas activates Wnt signaling and MG proliferation without retinal injury. Upstream of Wnt, deletion of GSK3beta stabilizes beta-catenin and activates MG proliferation. Downstream of Wnt, beta-catenin binds to the Lin28 promoter and activates transcription. Deletion of Lin28 abolishes beta-catenin mediated effects on MG proliferation, and Lin28 gene transfer stimulates MG proliferation. We further demonstrate that let-7 miRNAs are critically involved in Wnt/Lin28-regulated MG proliferation. Intriguingly, a subset of cell-cycle reactivated MGs express markers for amacrine cells. Together, these results reveal a key role of Wnt-Lin28-let7 miRNA signaling in regulating proliferation and neurogenic potential of MGs in the adult mammalian retina. PMID- 27681430 TI - MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs. AB - Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further characterize the dynamics and consequences of this transient cell state. Single-cell transcriptomics identified the earliest upregulated transcripts as cells enter the MERVL/Zscan4 state. The MERVL/Zscan4 transcriptional network was also upregulated during induced pluripotent stem cell reprogramming. Genome-wide DNA methylation and chromatin analyses revealed global DNA hypomethylation accompanying increased chromatin accessibility. This transient DNA demethylation was driven by a loss of DNA methyltransferase proteins in the cells and occurred genome-wide. While methylation levels were restored once cells exit this state, genomic imprints remained hypomethylated, demonstrating a potential global and enduring influence of endogenous retroviral activation on the epigenome. PMID- 27681431 TI - Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization. AB - CXCR4 plays a central role in B cell immune response, notably by promoting plasma cell (PC) migration and maintenance in the bone marrow (BM). Gain-of-function mutations in CXCR4 affecting receptor desensitization have been reported in the rare immunodeficiency called WHIM syndrome (WS). Despite lymphopenia, patients mount an immune response but fail to maintain it over time. Using a knockin mouse model phenocopying WS, we showed that, counter-intuitively, a gain of Cxcr4 function inhibited the maintenance of antibody titers after immunization. Although the Cxcr4 mutation intrinsically and locally promoted germinal center response and PC differentiation, antigen-specific PCs were barely detected in the BM, a defect mirrored by early accumulation of immature plasmablasts potentially occupying the survival niches for long-lived PCs. Therefore, fine-tuning of Cxcr4 desensitization is critically required for efficient PC differentiation and maintenance, and absence of such a regulatory process may account for the defective humoral immunity observed in WS patients. PMID- 27681432 TI - Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery. AB - Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naive commensal-reactive transgenic T cells expressing colonic Treg T cell receptors (TCRs) to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3(+) cells 1 week after transfer. Contrary to prior reports, Foxp3(+) cells underwent the most cell divisions, demonstrating that pTreg cell generation can be the dominant outcome from naive T cell activation. Moreover, Notch2-dependent, but not Batf3-dependent, dendritic cells were involved in Treg cell selection. Finally, neither deletion of the conserved nucleotide sequence 1 (CNS1) region in Foxp3 nor blockade of TGF-beta (transforming growth factor-beta)-receptor signaling completely abrogated Foxp3 induction. Thus, these data show that pTreg cell selection to commensal bacteria is rapid, is robust, and may be specified by TGF-beta-independent signals. PMID- 27681434 TI - Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity. AB - The extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. SPARC expression also results in the formation of a highly immunosuppressive microenvironment, composed by infiltrating T regulatory cells, mast cells, and myeloid-derived suppressor cells (MDSCs). The ability of SPARC to induce EMT depended on the localization and suppressive function of myeloid cells, and inhibition of the suppressive function MDSCs by administration of aminobisphosphonates could revert EMT, rendering SPARC-overexpressing tumor cells sensitive to Doxil. We conclude that that SPARC is regulating the interplay between MDSCs and the ECM to drive the induction of EMT in tumor cells. PMID- 27681433 TI - MALT1 Protease Activation Triggers Acute Disruption of Endothelial Barrier Integrity via CYLD Cleavage. AB - Microvascular endothelial cells maintain a tight barrier to prevent passage of plasma and circulating immune cells into the extravascular tissue compartment, yet endothelial cells respond rapidly to vasoactive substances, including thrombin, allowing transient paracellular permeability. This response is a cornerstone of acute inflammation, but the mechanisms responsible are still incompletely understood. Here, we demonstrate that thrombin triggers MALT1 to proteolytically cleave cylindromatosis (CYLD). Fragmentation of CYLD results in microtubule disruption and a cascade of events leading to endothelial cell retraction and an acute permeability response. This finding reveals an unexpected role for the MALT1 protease, which previously has been viewed mostly as a driver of pro-inflammatory NF-kappaB signaling in lymphocytes. Thus, MALT1 not only promotes immune cell activation but also acutely regulates endothelial cell biology, actions that together facilitate tissue inflammation. Pharmacologic inhibition of MALT1 may therefore have synergistic impact by targeting multiple disparate steps in the overall inflammatory response. PMID- 27681435 TI - Truncating Prolactin Receptor Mutations Promote Tumor Growth in Murine Estrogen Receptor-Alpha Mammary Carcinomas. AB - Estrogen receptor alpha-positive (ERalpha+) luminal tumors are the most frequent subtype of breast cancer. Stat1(-/-) mice develop mammary tumors that closely recapitulate the biological characteristics of this cancer subtype. To identify transforming events that contribute to tumorigenesis, we performed whole genome sequencing of Stat1(-/-) primary mammary tumors and matched normal tissues. This investigation identified somatic truncating mutations affecting the prolactin receptor (PRLR) in all tumor and no normal samples. Targeted sequencing confirmed the presence of these mutations in precancerous lesions, indicating that this is an early event in tumorigenesis. Functional evaluation of these heterozygous mutations in Stat1(-/-) mouse embryonic fibroblasts showed that co-expression of truncated and wild-type PRLR led to aberrant STAT3 and STAT5 activation downstream of the receptor, cellular transformation in vitro, and tumor formation in vivo. In conclusion, truncating mutations of PRLR promote tumor growth in a model of human ERalpha+ breast cancer and warrant further investigation. PMID- 27681437 TI - Loss of HDAC-Mediated Repression and Gain of NF-kappaB Activation Underlie Cytokine Induction in ARID1A- and PIK3CA-Mutation-Driven Ovarian Cancer. AB - ARID1A is frequently mutated in ovarian clear cell carcinoma (OCCC) and often co exists with activating mutations of PIK3CA. Although induction of pro inflammatory cytokines has been observed in this cancer, the mechanism by which the two mutations synergistically activate cytokine genes remains elusive. Here, we established an in vitro model of OCCC by introducing ARID1A knockdown and mutant PIK3CA into a normal human ovarian epithelial cell line, resulting in cell transformation and cytokine gene induction. We demonstrate that loss of ARID1A impairs the recruitment of the Sin3A-HDAC complex, while the PIK3CA mutation releases RelA from IkappaB, leading to cytokine gene activation. We show that an NF-kappaB inhibitor partly attenuates the proliferation of OCCC and improves the efficacy of carboplatin both in cell culture and in a mouse model. Our study thus reveals the mechanistic link between ARID1A/PIK3CA mutations and cytokine gene induction in OCCC and suggests that NF-kappaB inhibition could be a potential therapeutic option. PMID- 27681436 TI - Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration. AB - Long non-coding RNAs (lncRNAs) represent the largest and most diverse class of non-coding RNAs, comprising almost 16,000 currently annotated transcripts in human and 10,000 in mouse. Here, we investigated the role of lncRNAs in mammary tumors by performing RNA-seq on tumor sections and organoids derived from MMTV PyMT and MMTV-Neu-NDL mice. We identified several hundred lncRNAs that were overexpressed compared to normal mammary epithelium. Among these potentially oncogenic lncRNAs we prioritized a subset as Mammary Tumor Associated RNAs (MaTARs) and determined their human counterparts, hMaTARs. To functionally validate the role of MaTARs, we performed antisense knockdown and observed reduced cell proliferation, invasion, and/or organoid branching in a cancer specific context. Assessing the expression of hMaTARs in human breast tumors revealed that 19 hMaTARs are significantly upregulated and many of these correlate with breast cancer subtype and/or hormone receptor status, indicating potential clinical relevance. PMID- 27681440 TI - Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary. PMID- 27681438 TI - Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells. AB - DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse embryonic stem cells (mESCs) with varying DNA methylation levels to study the effects of DNA methylation on deposition of histone modifications. We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. This is reversed upon remethylation by Dnmt expression. DNA methylation promotes H3K27me3 deposition at bivalent promoters, while opposing H3K27me3 at silent promoters. DNA methylation also reversibly regulates H3K27ac and H3K27me3 at previously identified tissue-specific enhancers. These effects require DNMT catalytic activity. Collectively, our data show that DNA methylation is essential and instructive for deposition of specific histone modifications across regulatory regions, which together influences gene expression patterns in mESCs. PMID- 27681439 TI - DEEPN as an Approach for Batch Processing of Yeast 2-Hybrid Interactions. AB - We adapted the yeast 2-hybrid assay to simultaneously uncover multiple transient protein interactions within a single screen by using a strategy termed DEEPN (dynamic enrichment for evaluation of protein networks). This approach incorporates high-throughput DNA sequencing and computation to follow competition among a plasmid population encoding interacting partners. To demonstrate the capacity of DEEPN, we identify a wide range of ubiquitin-binding proteins, including interactors that we verify biochemically. To demonstrate the specificity of DEEPN, we show that DEEPN allows simultaneous comparison of candidate interactors across multiple bait proteins, allowing differential interactions to be identified. This feature was used to identify interactors that distinguish between GTP- and GDP-bound conformations of Rab5. PMID- 27681443 TI - Supporting Threat Management with Forensic Expert Knowledge: Protecting Public Officials and Private Individuals. AB - This article describes the implementation of a Cantonal Threat Assessment and Management (CTAM) in Zurich, Switzerland. In order to support this endeavor, the Specialist Unit for Forensic Assessment and Case Management was installed. The forensic experts provide supervision and short-term assessments to public prosecutors and general psychiatrists. In close cooperation with police threat management units, forensic experts support the assessment and management of individuals who exhibit concerning and threatening behavior towards public officials or private individuals. A public official case study illustrates this joint approach. The author's experience with CTAM, its pitfalls and the potential areas of improvement are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27681441 TI - White Matter Microstructural Alterations in Children with ADHD: Categorical and Dimensional Perspectives. AB - Studies of brain alterations in children with attention-deficit/hyperactivity disorder (ADHD) have shown heterogeneous results. The aims of the current study were to investigate white matter microstructure in children using both categorical and dimensional definitions of ADHD and to determine the functional consequences of observed alterations. In a large single-site sample of children (aged 8-15 years) with ADHD (n=83) and healthy controls (n=122), we used tract based spatial statistics on diffusion tensor imaging data to investigate whole skeleton differences of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD), and mode of anisotropy related to ADHD status (categorical) and symptom severity (dimensional). For categorical differences observed, we analyzed their association with cognitive functioning in working memory and inhibition. Compared with healthy controls, children with ADHD showed decreased FA and increased RD in widespread, overlapping brain regions, mainly in corpus callosum (CC) and major tracts in the left hemisphere. Decreased FA was associated with inhibition performance in the participants with ADHD. Using dimensional definitions, greater hyperactivity/impulsivity symptom severity was associated with higher FA also in widespread regions, mainly in CC and major tracts in the right hemisphere. Our study showed white matter alterations to be related to ADHD status and symptom severity in patients. The coexistence of decreased FA and increased RD in the absence of alterations in MD or AD might indicate altered myelination as a pathophysiological factor in ADHD. PMID- 27681442 TI - Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo Controlled Study. AB - The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18-70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50 mg, lanicemine 100 mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial. PMID- 27681445 TI - MPD3: a useful medicinal plants database for drug designing. AB - Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info . PMID- 27681446 TI - The evolution of optimal resource allocation and mating systems in hermaphroditic perennial plants. AB - By incorporating the effects of inbreeding depression (ID) on both juveniles and adults survivorship, we developed a new theoretical model for hermaphroditic perennial plants. Our model showed that the effect of the selfing rate on the evolutionarily stable strategy (ESS) reproductive allocation depends on three parameters: (1) the self-fertilized juvenile relative survivorship (SFJRS), (2) the self-fertilized adult relative survivorship (SFARS) and (3) the growth rate of self-fertilized adult, where the SFJRS is the survivorship of self-fertilized juveniles divided by the survivorship of outcrossed juveniles, and likewise for the SFARS. However, the ESS sex allocation decreases as the selfing rate increases. This relationship seems independent of the SFJRS, the SFARS, and the growth rate of self-fertilized adults. Additionally, our model showed that the complete outcrossing is an ESS when the fraction of juvenile inbreeding depression (FJID) is less than 1/2 - tau, where tau is the self-fertilized adults mortality rate caused by ID. In contrast, the complete selfing also acts as an ESS when the FJID is greater than 1/2 - tau. These results could explain the diversity of mating strategies and related resource allocations for plants. PMID- 27681444 TI - Remotely sensing the German Wadden Sea-a new approach to address national and international environmental legislation. AB - The Wadden Sea along the North Sea coasts of Denmark, Germany, and the Netherlands is the largest unbroken system of intertidal sand and mud flats in the world. Its habitats are highly productive and harbour high standing stocks and densities of benthic species, well adapted to the demanding environmental conditions. Therefore, the Wadden Sea is one of the most important areas for migratory birds in the world and thus protected by national and international legislation, which amongst others requires extensive monitoring. Due to the inaccessibility of major areas of the Wadden Sea, a classification approach based on optical and radar remote sensing has been developed to support environmental monitoring programmes. In this study, the general classification framework as well as two specific monitoring cases, mussel beds and seagrass meadows, are presented. The classification of mussel beds profits highly from inclusion of radar data due to their rough surface and achieves agreements of up to 79 % with areal data from the regular monitoring programme. Classification of seagrass meadows reaches even higher agreements with monitoring data (up to 100 %) and furthermore captures seagrass densities as low as 10 %. The main classification results are information on area and location of individual habitats. These are needed to fulfil environmental legislation requirements. One of the major advantages of this approach is the large areal coverage with individual satellite images, allowing simultaneous assessment of both accessible and inaccessible areas and thus providing a more complete overall picture. PMID- 27681447 TI - Pouchitis after ileal pouch-anal anastomosis in ulcerative colitis: Diagnosis, management, risk factors, and incidence. AB - Restorative proctocolectomy with ileal pouch-anal anastomosis has been the surgical treatment of choice for patients with ulcerative colitis who require surgery. Quality of life after this procedure is satisfactory in most cases; however, pouchitis is a troublesome condition involving inflammation of the ileal pouch. When a patient presents with symptoms of pouchitis, such as increased bowel movements, mucous and/or bloody exudates, abdominal cramps, and fever, endoscopy is essential for a precise diagnosis. The proximal ileum and rectal cuff, as well as the ileal pouch, should be endoscopically observed. The reported incidence of pouchitis ranges from 14% to 59%, and antibiotic therapy is the primary treatment for acute pouchitis. Chronic pouchitis includes antibiotic dependent and refractory pouchitis. Intensive therapy including antitumor necrosis factor antibodies and steroids may be necessary for antibiotic refractory pouchitis, and pouch failure may occur despite such intensive treatment. Reported risk factors for the development of pouchitis include presence of extraintestinal manifestations, primary sclerosing cholangitis, non smoking, and postoperative non-steroidal anti-inflammatory drug usage. In the present review, we focus on the diagnosis, endoscopic features, management, incidence, and risk factors of pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis. PMID- 27681448 TI - A Standardized "Rescue" Exercise Program for Symptomatic Flare-up of Knee Osteoarthritis: Description and Safety Considerations. AB - Study Design Secondary analysis of clinical trial data. Background Knee osteoarthritis (OA) management has changed significantly over recent decades toward nonpharmacological treatments, particularly exercise. However, the optimal exercise program remains to be established. Objective To describe the implementation of standardized rescue exercises for patients with pain exacerbations and to assess whether performing these benefit or further worsen symptoms in patients with exacerbated symptoms of knee OA. Methods The data from 2 randomized controlled studies of exercise in patients with knee OA were used. A supervised, standard exercise program that included standardized "rescue" exercises to be performed in the event of symptomatic exacerbation, defined as knee pain of greater than 5 on a 0-to-10 numeric pain-rating scale, was conducted for 12 weeks at 3 sessions per week. Pain ratings were obtained before and after each exercise session. Results Of 131 participants included, 2 never commenced the exercise program, leaving 129 to be included in the analysis. The analysis was observational and thus had no comparison group. During the program, 36 participants (28%) were referred to the rescue exercises. In 63% of the rescue sessions, the participants experienced decreased pain intensity (average +/- SD, 2.6 +/- 2.3), 27% reported no change in pain, and 10% reported increased pain intensity (average +/- SD, 1.3 +/- 0.5). Conclusion Having a predefined and standardized rescue exercise option appears beneficial, and did not result in further worsening of exacerbated knee OA symptoms. The intervention may be particularly relevant for patients with knee OA who have more severe symptoms. Level of Evidence Therapy, level 2b. Registered at www.clinicaltrials.gov (NCT01545258 and NCT01945749). J Orthop Sports Phys Ther 2016;46(11):942-946. Epub 28 Sep 2016. doi:10.2519/jospt.2016.6908. PMID- 27681449 TI - Dutch Translation and Cross-cultural Adaptation of the Lysholm Score and Tegner Activity Scale for Patients With Anterior Cruciate Ligament Injuries. AB - Study Design Clinical measurement. Background The Lysholm score and Tegner activity scale are frequently used patient-reported instruments to determine the functional status and activity level after anterior cruciate ligament (ACL) reconstruction. Objectives To translate and cross-culturally adapt the Lysholm score and Tegner activity scale for use in the Dutch population and to evaluate the reliability and validity of these questionnaires in individuals after ACL reconstruction. Methods The translation and adaptation were conducted in several steps according to the guidelines in the literature. The measurement properties of the Lysholm score and Tegner activity scale (internal consistency, construct validity, and floor and ceiling effects) were tested in 96 patients. Reproducibility was tested in 69 patients with ACL injuries. On the first occasion, the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) and RAND 36-Item Health Survey (RAND-36) were also administered. Results The Lysholm score and Tegner activity scale showed good test-retest reliability between repeated measures (intraclass correlation coefficient = 0.93 and 0.97, respectively) and reasonable to good internal consistency (Cronbach alpha = .70-.83). The Lysholm score had a very strong correlation with the IKDC (r = 0.83, P<.01) and moderate correlation with the RAND-36 (r = 0.55, P<.01). The Tegner activity scale had moderate correlations with both the IKDC (r = 0.42, P<.01) and RAND-36 (r = 0.48, P<.01). Conclusion The psychometric performance of the Lysholm score and the Tegner activity scale as outcome measures for Dutch patients after ACL reconstruction is acceptable. J Orthop Sports Phys Ther 2016;46(11):976-983. Epub 28 Sep 2016. doi:10.2519/jospt.2016.6566. PMID- 27681451 TI - NSAIDs and the failing heart. PMID- 27681450 TI - Fine-Needle Aspiration Biopsies of Ovarian Masses: A Reliable Technique. AB - OBJECTIVE: In gynecology, fine-needle aspiration (FNA) has an overall accuracy of 94.5% in differentiation between benign and malignant tumors. The purpose of this study was to determine reliable cytological criteria for categorizing ovarian masses into benign and malignant categories, their subtypes, and also to evaluate FNA accuracy in the diagnosis of ovarian tumors in relation to histopathological findings. STUDY DESIGN: A prospective study was performed on all patients with a preoperative diagnosis of ovarian tumor who were referred to our hospital between August 2013 and August 2015. During surgery, FNA was performed using an 18-gauge needle by a pathologist. Aspirated material was spread on clean glass slides and stained with Papanicolaou and Wright-Giemsa stains. The cytological findings and results were compared with the histological diagnosis. RESULTS: Of the 81 cases in this study, there was a discrepancy between the cytological and histological diagnosis in 9 cases. The overall cytological diagnostic accuracy in our study was 88.9% with a sensitivity and specificity of 78.1 and 95.5%, respectively. CONCLUSION: FNA of an ovarian mass is a minimally invasive procedure with acceptable diagnostic accuracy, especially when differentiating between benign and malignant lesions, and can be considered as a useful diagnostic modality for choosing an appropriate management course. PMID- 27681452 TI - Liver DCE-MRI Registration in Manifold Space Based on Robust Principal Component Analysis. AB - A technical challenge in the registration of dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging in the liver is intensity variations caused by contrast agents. Such variations lead to the failure of the traditional intensity based registration method. To address this problem, a manifold-based registration framework for liver DCE-MR time series is proposed. We assume that liver DCE-MR time series are located on a low-dimensional manifold and determine intrinsic similarities between frames. Based on the obtained manifold, the large deformation of two dissimilar images can be decomposed into a series of small deformations between adjacent images on the manifold through gradual deformation of each frame to the template image along the geodesic path. Furthermore, manifold construction is important in automating the selection of the template image, which is an approximation of the geodesic mean. Robust principal component analysis is performed to separate motion components from intensity changes induced by contrast agents; the components caused by motion are used to guide registration in eliminating the effect of contrast enhancement. Visual inspection and quantitative assessment are further performed on clinical dataset registration. Experiments show that the proposed method effectively reduces movements while preserving the topology of contrast-enhancing structures and provides improved registration performance. PMID- 27681453 TI - A comparative analysis of oral and maxillofacial pathology over a 16-year period, in the north of Portugal. AB - OBJECTIVES: To determine the frequency and spectrum of oral and maxillofacial lesions biopsied in a hospital population in the northern region of Portugal. METHODS: We conducted descriptive analyses of pathology reports from biopsies of oral and maxillofacial lesions performed between 1990 and 2006, in Oporto Hospital Center. Information on gender and age of patient, location of the lesions and the histopathological diagnosis were analysed. RESULTS: The analyses revealed that 1,520 (47.7%) patients were male and 1,666 (52.3%) were female. They had a mean age +/- standard deviation of 47.8 +/- 18.6 years. The site most frequently biopsied was the labial mucosa (17.5%). A non-neoplastic diagnosis was established in 2,162 (63.3%) cases, potentially malignant disorders in 163 (5.1%) and neoplasms in 886 (27.6%) (403 benign and 483 malignant). The most commonly reported diagnosis was fibroepithelial polyp (n = 186; 15.9%), followed by squamous cell carcinoma (SCC) (n = 158; 13.6%). SCC was the lesion most commonly found in male patients (n = 279; 18.4%) whilst fibroepithelial polyp was the lesion most commonly found in female patients (n = 268; 16.1%). The most common lesion in patients 0-17 years of age was a follicular cyst (n = 25; 12.8%), whereas in patients 18-64 years of age it was a fibroepithelial polyp (n = 299; 13%). SCC was the most common type of lesion found in patients >= 65 years of age (n = 160; 24.6%). CONCLUSION: This large sample provides useful information about the incidence and distribution of oral biopsies over a period of 16 years, allowing valuable comparison with other countries. Non-neoplastic lesions were the types of lesion most commonly reported, with fibroepithelial polyp being most frequent. SCC was the second most common diagnosis. PMID- 27681454 TI - Angiotensin-I-Converting Enzyme Inhibitory Activities and In Vivo Antihypertensive Effects of Sardine Protein Hydrolysate. AB - In our previous study, an antihypertensive protein hydrolysate was prepared from sardine. This study aimed to investigate the composition of sardine protein hydrolysate (SPH) and it's in vivo antihypertensive effect. SPH was separated sequentially with ultrafiltration and size exclusion chromatography. Fractions with high angiotensin-I-converting enzyme (ACE) inhibitory activity were further analyzed with RP-HPLC and amino acids analysis. Then, SPH was individually oral administrated to spontaneously hypertensive rats (SHR) and normotensive wistar kyoto rats (WKY) for 4 wk. After treatment, the systolic blood pressure (SBP), organ index, oxidative status, serum ACE activity, and serum angiotensin-II (ANG II) of all the rats were determined. According to the separation and analysis results, 3 main fractions with high ACE-inhibitory activity were obtained with different amino acids composition. The animal experiments results showed that SPH could significantly reduce SBP (P < 0.05 or P < 0.01) within 4 h after a single oral administration. After a chronic oral administration, a steady state of SBP in SHR rats was attained. The heart weight index and left ventricular weight index were significantly reduced (P < 0.05) in SPH-treated SHR rats. The malonyldialdehyde (MDA) levels in organs and serum, serum ACE activity, and serum ANG-II concentration in SPH-treated SHR rats were significantly lowered (P < 0.05 or P < 0.01) as compared to their controls. Meanwhile there was no significant effect (P > 0.05) on those parameters in WKY rats. These results indicate that SPH can decrease blood pressure in SHR rats and not in WKY rats. PMID- 27681455 TI - Management of pseudophakic myopic anisometropic amblyopia with piggyback Visian(r) implantable collamer lens. AB - PURPOSE: To assess the outcomes of sulcus implantation of the Visian(r) implantable collamer lens (ICL) to correct pseudophakic myopic anisometropic amblyopia with myopic shift and/or primary refractive overcorrection. METHODS: Prospective case series enrolled 14 pseudophakic eyes of 14 patients, 5-9 years old, with history of cataract surgery and primary in the bag-intraocular lenses (IOL) implantation, followed by myopic shift and/or refractive overcorrection and anisometropic amblyopia of variable degrees. All cases had implantation of a piggyback ICL/toric ICL, to correct the myopia/myopic astigmatism. Preoperatively, we evaluated the uncorrected distance visual acuity (UCVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent (MRSE), intraocular pressure (IOP) and endothelial cell density (ECD). We assessed the position and vaulting of the ICLs on slit lamp examination and confirmed by Scheimpflug tomography. Postoperative follow-up was at 1st week and 1, 3, 6, 9, 12, 18 and 24 months. RESULTS: Uncorrected distance visual acuity improved in all cases, and CDVA improved in 11 amblyopic eyes (2-4 lines). There was no evidence of interlenticular opacification (ILO) throughout the 2-year follow-up. Two cases were complicated with early postoperative acute elevation of IOP and were controlled with topical beta-blockers. Postoperative acute anterior uveitis occurred in six eyes and controlled by topical steroids. Implantable collamer lens (ICL) vault was measured using Pentacam, with mean value of 470 +/- 238 MUm. CONCLUSION: Sulcus implantation of the secondary piggyback ICL to correct unilateral pseudophakic myopic refractive error in children was safe, efficient, predictable and well tolerated in management of anisometropic amblyopia in all eyes. PMID- 27681456 TI - Relationships between heart-rate variability and pulse-rate variability obtained from video-PPG signal using ZCA. AB - In this paper, classical time- and frequency-domain variability indexes obtained by pulse rate variability (PRV) series extracted from video-photoplethysmography signals (vPPG) were compared with heart rate variability (HRV) parameters extracted from ECG signals. The study focuses on the analysis of the changes observed during a rest-to-stand manoeuvre (a mild sympathetic stimulus) performed on 60 young, normal subjects (age: [Formula: see text] years). The objective is to evaluate if video-derived PRV indexes may replace HRV in the assessment of autonomic responses to external stimulation. Video recordings were performed with a GigE Sony XCG-C30C camera and analyzed offline to extract the vPPG signal. A new method based on zero-phase component analysis (ZCA) was employed in combination with a fully-automatic method for detection and tracking of region of interest (ROI) located on the forehead, the cheek and the nose. Results show an overall agreement between time and frequency domain indexes computed on HRV and PRV series. However, some differences exist between resting and standing conditions. During rest, all the indexes computed on HRV and PRV series were not statistically significantly different (p > 0.05), and showed high correlation (Pearson's r > 0.90). The agreement decreases during standing, especially for the high-frequency, respiration-related parameters such as RMSSD (r = 0.75), pNN50 (r = 0.68) and HF power (r = 0.76). Finally, the power in the LF band (n.u.) was observed to increase significantly during standing by both HRV ([Formula: see text] versus [Formula: see text] (n.u.); rest versus standing) and PRV ([Formula: see text] versus [Formula: see text](n.u.); rest versus standing) analysis, but such an increase was lower in PRV parameters than that observed by HRV indexes. These results provide evidence that some differences exist between variability indexes extracted from HRV and video-derived PRV, mainly in the HF band during standing. However, despite these differences video-derived PRV indexes were able to evince the autonomic responses expected by the sympathetic stimulation induced by the rest-to-stand manoeuvre. PMID- 27681457 TI - Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia. AB - : Essentials Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. Basement membrane and interstitial matrix turnover changed significantly following hemarthrosis. SUMMARY: Background Hemophilic arthropathy is a severe complication of hemophilia. It is caused by recurrent bleeding into joint cavities, which leads to synovial inflammation, fibrosis, cartilage degradation and bone remodeling. Extracellular matrix remodeling of affected tissues is a hallmark of these pathological processes. Objectives The aim of this study was to use serological biomarkers of collagen turnover to evaluate extracellular matrix remodeling in a factor VIII-deficient rat model of hemophilic arthropathy. Methods F8-/- rats and wild-type littermate controls were subjected to repeated knee bleeds induced by needle puncture on days 0 and 14. Development of arthropathy was confirmed by histology after termination on day 28. Serum samples were collected at baseline and throughout the study and analyzed for biomarkers of collagen turnover, including collagens of the basement membrane (type IV collagen), the interstitial matrix (collagen types III, V and VI) and cartilage (type II collagen). Results In F8-/- rats, induced knee bleeding and subsequent development of arthropathy caused significant alterations in collagen turnover, measured as changes in serological biomarkers of basement membrane turnover, interstitial matrix turnover and cartilage degradation. Biomarkers of type II collagen degradation correlated significantly with cartilage degradation and degree of arthropathy. Hemophilic rats had a 50% higher turnover of the basement membrane than wild-type littermates at baseline. Conclusions Joint bleeding and hemophilic arthropathy cause changes in turnover of extracellular matrix collagens in hemophilic rats. Biomarkers of collagen turnover may be used to monitor joint bleeding and development of blood-induced joint disease in hemophilia. PMID- 27681458 TI - Local quantum thermal susceptibility. AB - Thermodynamics relies on the possibility to describe systems composed of a large number of constituents in terms of few macroscopic variables. Its foundations are rooted into the paradigm of statistical mechanics, where thermal properties originate from averaging procedures which smoothen out local details. While undoubtedly successful, elegant and formally correct, this approach carries over an operational problem, namely determining the precision at which such variables are inferred, when technical/practical limitations restrict our capabilities to local probing. Here we introduce the local quantum thermal susceptibility, a quantifier for the best achievable accuracy for temperature estimation via local measurements. Our method relies on basic concepts of quantum estimation theory, providing an operative strategy to address the local thermal response of arbitrary quantum systems at equilibrium. At low temperatures, it highlights the local distinguishability of the ground state from the excited sub-manifolds, thus providing a method to locate quantum phase transitions. PMID- 27681460 TI - Current Management of Intracranial Subarachnoid Hemorrhage. AB - Subarachnoid hemorrhage affects more than 25,000 Americans yearly and is most commonly caused by a ruptured, saccular, cerebral aneurysm. Current measures to evaluate and manage patients with nontraumatic subarachnoid hemorrhage are detailed. Areas of future progress are presented. The diagnosis and treatment of intracranial subarachnoid hemorrhage represent a medical and surgical emergency. PMID- 27681461 TI - Intracerebral Hemorrhage. AB - Stroke is a life threatening condition and remains the most common neurologic cause of hospital admission. Approximately 500,000 new or recurrent strokes are recorded each year in the United States. Behind cardiovascular disease and cancer, stroke remains the third leading cause of death in the United States, accounting for approximately 150,000 fatalities per year. Approximately 15%-20% of strokes are hemor-rhagic. This article focuses on intracerebral hemorrhage, which accounts for approximately half of stroke-related deaths. PMID- 27681459 TI - Detecting individual extracellular vesicles using a multicolor in situ proximity ligation assay with flow cytometric readout. AB - Flow cytometry is a powerful method for quantitative and qualitative analysis of individual cells. However, flow cytometric analysis of extracellular vesicles (EVs), and the proteins present on their surfaces has been hampered by the small size of the EVs - in particular for the smallest EVs, which can be as little as 40 nm in diameter, the limited number of antigens present, and their low refractive index. We addressed these limitations for detection and characterization of EV by flow cytometry through the use of multiplex and multicolor in situ proximity ligation assays (in situ PLA), allowing each detected EV to be easily recorded over background noise using a conventional flow cytometer. By targeting sets of proteins on the surface that are specific for distinct classes of EVs, the method allows for selective recognition of populations of EVs in samples containing more than one type of EVs. The method presented herein opens up for analyses of EVs using flow cytometry for their characterization and quantification. PMID- 27681462 TI - Neuro-Ophthalmologic Rehabilitation after Stroke. AB - Cerebrovascular disease may affect vision in a variety of ways. Stroke involving the afferent visual pathways typically causes visual field loss with or without defects in higher cortical processing. Damage to the efferent visual system may result in gaze palsy, diplopia, or fixational instability. Treatment modalities for these deficits include optical devices, extraocular muscle surgery, and pharmacologic agents. Neuro-ophthalmo- logic evaluation of the patient with visual problems following a stroke should include a thorough examination, realistic prognostic information, assessment of vocational visual needs, and initiation of any appropriate treatment. PMID- 27681463 TI - Spinal Cord Infarction. AB - Spinal cord infarction (SCI) is uncommon and, therefore, not extensively studied. Little is known about the epidemiology and individual risk factors for SCI. The prognosis for functional recovery after SCI from any cause is not well documented. Despite these deficiencies, useful clinical information regarding SCI following surgical procedures is available. Many nonsurgical causes of SCI are also recognized, including aortic pathology, systemic hypoperfusion, atherosclerotic emboli, or other embolic materials. An understanding of the patterns of blood supply to the spinal cord and the more common causes of SCI will aid in guiding future trials of neuroprotective medications, growth factors, and various perioperative techniques aimed at decreasing functional disability following SCI. PMID- 27681464 TI - Deep Vein Thrombosis and Pulmonary Embolism in Stroke. PMID- 27681465 TI - Managing under Managed Care. PMID- 27681466 TI - Report on the American Speech-Language- Hearing Association Functional Assessment of Communication Skills for Adults. PMID- 27681467 TI - My Stroke. PMID- 27681468 TI - Letters to the Editors. PMID- 27681469 TI - From the editor. PMID- 27681470 TI - Severe infantile male encephalopathy is a result of early post-zygotic WDR45 somatic mutation. PMID- 27681472 TI - San Antonio Summer '64. PMID- 27681471 TI - High-Frequency 1H NMR Chemical Shifts of SnII and PbII Hydrides Induced by Relativistic Effects: Quest for PbII Hydrides. AB - The role of relativistic effects on 1H NMR chemical shifts of SnII and PbII hydrides is investigated by using fully relativistic DFT calculations. The stability of possible PbII hydride isomers is studied together with their 1H NMR chemical shifts, which are predicted in the high-frequency region, up to 90 ppm. These 1H signals are dictated by sizable relativistic contributions due to spin orbit coupling at the heavy atom and can be as large as 80 ppm for a hydrogen atom bound to PbII. Such high-frequency 1H NMR chemical shifts of PbII hydride resonances cannot be detected in the 1H NMR spectra with standard experimental setup. Extended 1H NMR spectral ranges are thus suggested for studies of PbII compounds. Modulation of spin-orbit relativistic contribution to 1H NMR chemical shift is found to be important also in the experimentally known SnII hydrides. Because the 1H NMR chemical shifts were found to be rather sensitive to the changes in the coordination sphere of the central metal in both SnII and PbII hydrides, their application for structural investigation is suggested. PMID- 27681473 TI - Night Visiting. PMID- 27681474 TI - Dehydrosulfurative C-N Cross-Coupling and Concomitant Oxidative Dehydrogenation for One-Step Synthesis of 2-Aryl(alkyl)aminopyrimidines from 3,4-Dihydropyrimidin 1H-2-thiones. AB - A method for the synthesis of 2-aryl(alkyl)aminopyrimidines from readily available 3,4-dihydropyrimidin-1H-2-thiones (DHPMs) via dehydrosulfurative C-N cross-coupling and concomitant oxidative dehydrogenation under a Pd/Cu catalytic system is described. This reaction protocol provides unprecedented diversity of fully substituted 2-aryl(alkyl)aminopyrimidines in a single step from a wide range of DHPMs and amine coupling partners. PMID- 27681475 TI - 'AND' logic gates at work: Crystal structure of Rad53 bound to Dbf4 and Cdc7. AB - Forkhead-associated (FHA) domains are phosphopeptide recognition modules found in many signaling proteins. The Saccharomyces cerevisiae protein kinase Rad53 is a key regulator of the DNA damage checkpoint and uses its two FHA domains to interact with multiple binding partners during the checkpoint response. One of these binding partners is the Dbf4-dependent kinase (DDK), a heterodimer composed of the Cdc7 kinase and its regulatory subunit Dbf4. Binding of Rad53 to DDK, through its N-terminal FHA (FHA1) domain, ultimately inhibits DDK kinase activity, thereby preventing firing of late origins. We have previously found that the FHA1 domain of Rad53 binds simultaneously to Dbf4 and a phosphoepitope, suggesting that this domain functions as an 'AND' logic gate. Here, we present the crystal structures of the FHA1 domain of Rad53 bound to Dbf4, in the presence and absence of a Cdc7 phosphorylated peptide. Our results reveal how the FHA1 uses a canonical binding interface to recognize the Cdc7 phosphopeptide and a non canonical interface to bind Dbf4. Based on these data we propose a mechanism to explain how Rad53 enhances the specificity of FHA1-mediated transient interactions. PMID- 27681476 TI - Squamous cell carcinoma complicating a chronic lesion of hidradenitis suppurativa: a case report and review of the literature. AB - Squamous cell carcinoma (SCC) arising from chronic hidradenitis suppurativa (HS) is rare; however, the morbidity associated with this presentation is high and management has not been standardised or optimised. We present a case of HS of the perineum and buttocks complicated by SCC, requiring multiple extensive surgical resections. Adjuvant radiotherapy was withheld initially because of concern for poor healing of the surgical wound but was eventually initiated after a second recurrence was identified. The patient ultimately expired 4 years after the initial diagnosis of SCC. We also review 80 cases of SCC complicating HS found in the English literature. Case reports and mechanistic studies suggest the possibility that human papilloma virus and smoking may be risk factors associated with SCC in HS. Despite the majority of SCC cases being well-differentiated tumours in HS, the highly aggressive nature of SCC in HS and its high likelihood for rapid progression, recurrence, metastasis and high mortality suggests the need to advocate for aggressive treatment. We recommend an aggressive approach to management at the time of SCC diagnosis in HS, which includes appropriate imaging to establish the extent of the tumour, large and deep surgical excision, sentinel lymph node evaluation, consultation with radiation oncology for potential adjuvant radiation therapy and close surveillance. PMID- 27681477 TI - Caregiver burden and prevalence of depression, anxiety and sleep disturbances in Alzheimer's disease caregivers in China. AB - AIMS AND OBJECTIVES: To evaluate caregiver burden and factors that influence this burden among caregivers and patients with Alzheimer's disease in China. BACKGROUND: Long-term care can reduce the quality of life for caregivers and result in both mental and physical exhaustion. However, little is known about caregiver burden and associated factors in China. DESIGN: The study had a quantitative cross-sectional design. METHODS: A total of 309 caregivers and their patients were included in the study. The patients' cognitive, psychological and functional status and their caregivers' burden, sleep quality and mental state were evaluated. Descriptive analyses, single-factor regression and stepwise factor regression were used to determine the effects of various factors on caregiver burden. RESULTS: Older females and spouses still play an important role in providing family care for those with dementia. Most of the caregivers were the sole full-time caregiver and had little time for themselves. Sleepiness was a common physical problem for caregivers, and some of them had moderate to severe depression and anxiety. A lower functional status of the patient was associated with higher caregiver burden. Poorer physical status compared with before caregiving began, lower life satisfaction, and higher degrees of depression and anxiety were associated with higher caregiver burden. CONCLUSION: Depression, anxiety and sleep problems are the main challenges that are faced by family caregivers of patients with Alzheimer's disease. Caregivers' functional status, lower life satisfaction, depression and anxiety influenced caregiver burden. Caregiver burden was related to the severity of the patient's dementia and the personal factors of the caregivers. RELEVANCE TO CLINICAL PRACTICE: To provide information about caregivers' current status while caring for patients with Alzheimer's disease and to understand caregiver burden and its related factors. Professionals who work with Alzheimer's disease should pay more attention to caregiver burden, especially those with mental and physical problems. PMID- 27681478 TI - Changes in Species Richness and Composition of Tiger Moths (Lepidoptera: Erebidae: Arctiinae) among Three Neotropical Ecoregions. AB - Parana, Yungas and Chaco Serrano ecoregions are among the most species-rich terrestrial habitats at higher latitude. However, the information for tiger moths, one of the most speciose groups of moths, is unknown in these ecoregions. In this study, we assess their species richness and composition in all three of these ecoregions. Also we investigated whether the species composition of tiger moths is influenced by climatic factors and altitude. Tiger moth species were obtained with samples from 71 sites using standardized protocols (21 sites were in Yungas, 19 in Parana and 31 in Chaco Serrano). Rarefaction-extrapolation curves, non-parametric estimators for incidence and sample coverage indices were performed to assess species richness in the ecoregions studied. Non metric multidimensional scaling and adonis tests were performed to compare the species composition of tiger moths among ecoregions. Permutest analysis and Pearson correlation were used to evaluate the relationship among species composition and annual mean temperature, annual temperature range, annual precipitation, precipitation seasonality and altitude. Among ecoregions Parana was the richest with 125 species, followed by Yungas with 63 species and Chaco Serrano with 24 species. Species composition differed among these ecoregions, although Yungas and Chaco Serrano were more similar than Parana. Species composition was significantly influenced by climatic factors and altitude. This study showed that species richness and species composition of tiger moths differed among the three ecoregions assessed. Furthermore, not only climatic factors and altitude influence the species composition of tiger moths among ecoregions, but also climatic seasonality at higher latitude in Neotropical South America becomes an important factor. PMID- 27681479 TI - How do Australians living with MS experience oral health and accessing dental care? A focus group study. AB - OBJECTIVES: The symptoms of multiple sclerosis (MS) can affect oral care and access to dental services, but there is limited literature describing the oral health and perceived oral healthcare needs of people with MS. This study aimed to explore the oral health experiences, oral health behaviours and barriers to accessing dental care perceived by people living with MS in Australia. METHODS: Six focus groups were held across two metropolitan areas (Brisbane, Queensland and Melbourne, Victoria) and one regional area (Toowoomba, Queensland). Focus group data were analysed using thematic analysis. RESULTS: Living with MS was a highly individual experience due to the range of symptoms that may be experienced. In addition to having different symptom experiences to others with MS, individual symptoms also differed on a daily basis as the disease relapsed and remitted. The physical expressions of MS directly and indirectly affected the oral health of participants. Additionally, oral health was affected by the side effects of medications and orofacial pain symptoms. Depending on the symptoms experienced by the individual, personal oral hygiene was affected and professional dental appointments were difficult. Participants also experienced structural barriers to accessing professional dental care including difficulty accessing transport to-and-from dental appointments, space limitations in the dental surgery and financial barriers to care. DISCUSSION: Dental care was perceived to be inflexible and was not tailored to individual experiences of MS, which contributed to perceptions of poor quality and appropriateness of care. It is important for dental professionals to offer tailored and individualized dental care when treating people with MS. Our findings suggest that there needs to be greater interprofessional communication and referral to manage atypical dental pain symptoms. Oral health education for people with MS should include altered strategies to performing daily oral hygiene, the management of xerostomia and advice regarding low cariogenic diets suitable for dysphagia. Additionally, policy and strategies to improve the oral health of people with MS should focus on enhancing access through transport, reducing the cost of dental services to the individual and providing domiciliary oral health care. PMID- 27681481 TI - Occupation-based intervention versus rote exercise in modified constraint-induced movement therapy for patients with median and ulnar nerve injuries: a randomized controlled trial. AB - OBJECTIVE: To investigate effect of practice type during modified constraint induced movement therapy on hand function in patients with chronic median and ulnar nerve injuries. DESIGN: A prospective, single-blinded, randomized controlled clinical trial. SETTING: Participants' private home. SUBJECTS: A convenience sample of 36 outpatient participants allocated randomly to three equal groups. INTERVENTIONS: Intervention groups underwent 3-hour intensive training of affected hand each day, 3-day a week, 4-week in association with immobilisation of healthy hand: occupation-based group practiced meaningful occupations while rote exercise-based group performed rote exercises during constraint-induced movement therapy. Control group performed different activities with affected hand for 1.5-hour each day during 4-week without restriction of healthy hand. MAIN MEASURES: A blinded assessor tested Canadian occupational performance measure, box and block, Static two-point discrimination, disabilities of arm, shoulder, hand questionnaire, and self-assessment manikin in a random order across sessions 3-time as baseline (pre-test), after 4-week intervention (post-test), and 1-month after intervention period (follow up). RESULTS: Scores significantly changed in intervention groups compared to control. Despite significantly more improvement in occupation-based than rote exercise-based group in subjective measures at post-test and follow up (Canadian occupational performance measure: mean change 4.7 vs. 2.1 for performance, P< 0.001 and mean change 5.3 vs. 2.6 for satisfaction, P< 0.001), it was significant just at follow up for box and block and static two-point discrimination. CONCLUSIONS: Practice content of constraint-induced movement therapy is a critical part of its effectiveness on improving outcomes following peripheral nerve repair in favour of occupation-based intervention in present study. PMID- 27681482 TI - Homozygous SLCO2A1 translation initiation codon mutation in a Pakistani family with recessive isolated congenital nail clubbing. PMID- 27681480 TI - What environmental factors influence resumption of valued activities post stroke: a systematic review of qualitative and quantitative findings. AB - OBJECTIVE: Identify the environmental factors that influence stroke-survivors' reengagement in personally valued activities and determine what specific environmental factors are related to specific valued activity types. DATA SOURCES: PubMed, CINAHL and PsycINFO were searched until June 2016 using multiple search-terms for stroke, activities, disability, and home and community environments. REVIEW METHODS: An integrated mixed-method systematic review of qualitative, quantitative and mixed-design studies was conducted. Two researchers independently identified relevant studies, assessed their methodological quality and extracted relevant findings. To validly compare and combine the various findings, all findings were classified and grouped by environmental category and level of evidence. RESULTS: The search yielded 4024 records; 69 studies were included. Most findings came from low-evidence-level studies such as single qualitative studies. All findings were consistent in that the following factors facilitated reengagement post-stroke: personal adapted equipment; accessible environments; transport; services; education and information. Barriers were: others' negative attitudes and behaviour; long distances and inconvenient environmental conditions (such as bad weather). Each type of valued activity, such as mobility or work, had its own pattern of environmental influences, social support was a facilitator to all types of activities. Although in many qualitative studies others' attitudes, behaviour and stroke-related knowledge were seen as important for reengagement, these factors were hardly studied quantitatively. CONCLUSION: A diversity of environmental factors was related to stroke-survivors' reengagement. Most findings came from low-evidence-level studies so that evidence on causal relationships was scarce. In future, more higher-level-evidence studies, for example on the attitudes of significant others, should be conducted. PMID- 27681483 TI - Autonomy and integration in complex parasite life cycles. AB - Complex life cycles are common in free-living and parasitic organisms alike. The adaptive decoupling hypothesis postulates that separate life cycle stages have a degree of developmental and genetic autonomy, allowing them to be independently optimized for dissimilar, competing tasks. That is, complex life cycles evolved to facilitate functional specialization. Here, I review the connections between the different stages in parasite life cycles. I first examine evolutionary connections between life stages, such as the genetic coupling of parasite performance in consecutive hosts, the interspecific correlations between traits expressed in different hosts, and the developmental and functional obstacles to stage loss. Then, I evaluate how environmental factors link life stages through carryover effects, where stressful larval conditions impact parasites even after transmission to a new host. There is evidence for both autonomy and integration across stages, so the relevant question becomes how integrated are parasite life cycles and through what mechanisms? By highlighting how genetics, development, selection and the environment can lead to interdependencies among successive life stages, I wish to promote a holistic approach to studying complex life cycle parasites and emphasize that what happens in one stage is potentially highly relevant for later stages. PMID- 27681484 TI - The Pharmacokinetics of Beraprost Sodium Following Single Oral Administration to Subjects With Impaired Kidney Function. AB - The purpose of the present study was to evaluate the pharmacokinetics of beraprost sodium (BPS) and its active enantiomer, BPS-314d, in Japanese subjects with impaired kidney function. The plasma and urine concentrations of BPS and BPS 314d were measured following the single oral administration of 120 MUg of BPS as the sustained-release tablet, TRK-100STP, under fasting conditions to 18 subjects with impaired kidney function (stage 2, 3, and 4 chronic kidney disease [CKD] as categorized by the estimated glomerular filtration rate) and to 6 age-, body weight-, and gender-matched subjects with normal kidney function (stage 1 CKD). The Cmax values (mean +/- SD) of BPS in stage 1, 2, 3, and 4 CKD, respectively, were 84.9 +/- 22.9, 119.8 +/- 36.4, 190.6 +/- 137.3, and 240.2 +/- 110.5 pg/mL; its AUC0-48h were 978 +/- 226, 1252 +/- 427, 1862 +/- 964, and 1766 +/- 806 pg.h/mL, respectively, and its cumulative urinary excretion rates were 0.704 +/- 0.351%, 0.638 +/- 0.292%, 0.485 +/- 0.294%, and 0.159 +/- 0.136%. The Cmax values of BPS-314d were 22.4 +/- 6.4, 30.8 +/- 8.5, 46.7 +/- 30.6, and 54.4 +/- 25.2 pg/mL, its AUC0-48h were 155 +/- 56, 226 +/- 67, 341 +/- 176, and 329 +/- 143 pg.h/mL, and its cumulative urinary excretion rates were 0.428 +/- 0.242%, 0.349 +/- 0.179%, 0.356 +/- 0.270%, and 0.096 +/- 0.099%, respectively. Adverse events were reported in 2 subjects with stage 2 CKD and 1 subject with stage 4 CKD. The Cmax and AUC0-48h of BPS and BPS-314d were higher based on the severity of impaired kidney function. No relationship was observed between the incidence of adverse events and the severity, and tolerability was confirmed. We consider that dose adjustment is not necessary, but BPS is more carefully treated in patients with impaired kidney function. PMID- 27681486 TI - Vitamin A supplementation for the prevention of morbidity and mortality in infants one to six months of age. AB - BACKGROUND: Vitamin A deficiency is a significant public health problem in low- and middle-income countries. Vitamin A supplementation provided to infants less than six months of age is one of the strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity. OBJECTIVES: To evaluate the effect of synthetic vitamin A supplementation in infants one to six months of age in low- and middle-income countries, irrespective of maternal antenatal or postnatal vitamin A supplementation status, on mortality, morbidity and adverse effects. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed (1966 to 5 March 2016), Embase (1980 to 5 March 2016) and CINAHL (1982 to 5 March 2016). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised, individually or cluster randomised trials involving synthetic vitamin A supplementation compared to placebo or no intervention provided to infants one to six months of age were eligible. DATA COLLECTION AND ANALYSIS: Two review authors assessed the studies for eligibility and assessed their risk of bias and collected data on outcomes. MAIN RESULTS: The review included 12 studies (reported in 22 publications). The included studies assigned 24,846 participants aged one to six months to vitamin A supplementation or control group. There was no effect of vitamin A supplementation for the primary outcome of all-cause mortality based on seven studies that included 21,339 (85%) participants (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.89 to 1.25; I2 = 0%; test for heterogeneity: P = 0.79; quality of evidence: moderate). Also, there was no effect of vitamin A supplementation on mortality or morbidity due to diarrhoea and respiratory tract infection. There was an increased risk of bulging fontanelle within 24 to 72 hours of supplementation in the vitamin A group compared to control (RR 3.10, 95% CI 1.89 to 5.09; I2 = 9%, test for heterogeneity: P = 0.36; quality of evidence: high). There was no reported subsequent increased risk of death, convulsions or irritability in infants who developed bulging fontanelle after vitamin A supplementation, and it resolved in most cases within 72 hours. There was no increased risk of other adverse effects such as vomiting, irritability, diarrhoea, fever and convulsions in the vitamin A supplementation group compared to control. Vitamin A supplementation did not have any statistically significant effect on vitamin A deficiency (RR 0.86, 95% CI 0.70 to 1.06; I2 = 27%; test for heterogeneity: P = 0.25; quality of evidence: moderate). AUTHORS' CONCLUSIONS: There is no convincing evidence that vitamin A supplementation for infants one to six months of age results in a reduction in infant mortality or morbidity in low- and middle-income countries. There is an increased risk of bulging fontanelle with vitamin A supplementation in this age group; however, there were no reported subsequent complications because of this adverse effect. PMID- 27681485 TI - Improved heterologous production of the nonribosomal peptide-polyketide siderophore yersiniabactin through metabolic engineering and induction optimization. AB - Biosynthesis of complex natural products like polyketides and nonribosomal peptides using Escherichia coli as a heterologous host provides an opportunity to access these molecules. The value in doing so stems from the fact that many compounds hold some therapeutic or other beneficial property and their original production hosts are intractable for a variety of reasons. In this work, metabolic engineering and induction variable optimization were used to increase production of the polyketide-nonribosomal peptide compound yersiniabactin, a siderophore that has been utilized to selectively remove metals from various solid and aqueous samples. Specifically, several precursor substrate support pathways were altered through gene expression and exogenous supplementation in order to boost production of the final compound. The gene expression induction process was also analyzed to identify the temperatures and inducer concentrations resulting in highest final production levels. When combined, yersiniabactin production was extended to ~175 mg L-1 . (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1412-1417, 2016. PMID- 27681487 TI - Arterial hemodynamics are impaired at rest and following acute exercise in overweight young men. AB - Higher body mass index (BMI) is associated with greater cardiovascular disease (CVD) risk, in part due to aortic stiffening assessed by carotid-femoral pulse wave velocity (cfPWV). Importantly, greater cardiorespiratory fitness (CRF; VO2peak) decreases CVD risk, and is associated with reductions in aortic stiffness. We tested the hypothesis that young adult overweight (OW, n=17) compared with healthy-weight (HW, n=17) men will have greater resting aortic stiffness, reduced CRF and an impaired post-exercise hemodynamic response. Resting cfPWV was greater in OW versus HW individuals (5.81 +/- 0.13 vs 4.81 +/- 0.12 m/sec, p<0.05). Relative CRF (VO2peak; mL/kg/min) was lower in OW compared with HW individuals (49.4 +/- 1.3 vs 57.6 +/- 1.0 mL/kg/min, p<0.05), and was inversely related with cfPWV (p<0.05). However, CRF as absolute VO2peak (L/min) was not different between groups and there was no relation between cfPWV and absolute VO2peak (L/min), indicating reduced relative CRF in OW men is due to greater body mass. Following the maximal treadmill exercise test, cfPWV was greater in OW compared with HW subjects from rest to 60 minutes post-exercise (p<0.05). Compared with HW, OW individuals had higher systolic blood pressure (main effect, p<0.05) and diastolic blood pressure was selectively increased for up to 60 minutes following exercise (p<0.05). Overweight individuals had an attenuated post-exercise decrease in mean arterial pressure (p<0.05). Collectively, these results indicate that young, apparently healthy, OW men have greater resting aortic stiffening and an impaired post-exercise hemodynamic response. PMID- 27681488 TI - Cold-associated painful purple digits due to type I cryoglobulinemia. PMID- 27681491 TI - Basic methods for the assessment of health-related quality of life in uro oncological patients. AB - BACKGROUND: The evaluation of patients' expectations and quality of life in uro oncology is considered an important outcome of treatment efficacy and satisfaction. Aim of this systematic review was to evaluate the most frequently adopted tools in uro-oncology to assess Health Related Quality of Life (HRQoL). EVIDENCE ACQUISITION: A systematic literature search until October 2015 was performed on MEDLINE, Cochrane Library, PubMed combining the following terms: "quality of life," "health-related quality of life," "kidney cancer," "bladder cancer," "prostate cancer." Additional references were obtained from the reference list of full-text manuscripts. Data were synthesized using meta analytic methods conformed to the PRISMA statement. EVIDENCE SYNTHESIS: HRQoL is a fundamental step in evaluating treatment outcome in patients with urological cancers. HRQoL is mostly measured through several questionnaires, which are generally categorized in generic questionnaires, exploring the patient's well being en bloc; specific questionnaires, assessing each single domain of health status; and uro-oncological specific questionnaires, mainly characterized by a modular approach. Although different questionnaires have been proposed and validated, the standard method to be adopted in urology is far from the solution and further studies should investigate the strength and weakness of the different questionnaires. CONCLUSIONS: HRQoL questionnaires should become a standard method to evaluate medical/surgical outcomes in uro-oncology. Their implementation may significantly improve patients' satisfaction and help physicians in the decision making process and possibly reduce health care costs. PMID- 27681492 TI - Robot assisted retroperitoneal lymph-node dissection after adjuvant therapy: different indications. AB - BACKGROUND: Today, access to technology through robotic surgery has allowed urologists to have a valuable tool in order to perform various robot -assisted laparoscopic procedures. Robotic surgery allows reproducing complex techniques such as retroperitoneal or extended pelvic lymphadenectomy. The aim of the study was to report our series of robot assisted retroperitoneal lymphadenectomy and to demonstrate its technical and oncological feasibility. METHODS: A retrospective analysis on 7 patients (four cases of testicular tumors, one prostate adenocarcinoma, and two bladder urothelial carcinomas), who underwent retroperitoneal para-aortic, interaorto-cava and extended pelvic lymphadenectomy by robot assisted laparoscopic surgery, was conducted. We analyzed demographic, oncologic and operative data (surgical time, blood loss, and hospital stay). RESULTS: Demographic and operative data showed a mean age of 49 years (18-65), mean BMI of 26.1 kg/m2(23.7-29.1), mean operative time of198 minutes (180-220), mean estimated blood loss of 88 mL, and mean hospital stay of 3.6 days (3-5). No intraoperative complications occurred. Themean number of dissected nodes was 12 (3-20). Histopathology findings showed one case of postchemotherapy recurrenceof seminoma and six cases of fibrosis. At a mean postoperative follow-up of 39 months (7-75) no patients showed disease recurrence. CONCLUSIONS: Our case series demonstrated that the robot assisted approach isa feasible and reproducible option in skilled robotic surgical referral centers. The surgeons' experience and the optical magnification, associated to the degree of freedom offered by robotic assisted laparoscopy allow achievinga precise lymph node dissection, also in advanced oncologic patients. PMID- 27681493 TI - New treatment strategies for benign prostatic hyperplasia in the frail elderly population: a systematic review. AB - INTRODUCTION: Life expectancy is constantly increasing and as a consequence older men, frequently with multiple comorbidities, are seeking treatment for benign prostatic hyperplasia. Given their frail health, these men need extreme attention in their management, as efficacious and safe treatment strategies in the general population may not be adequate for them. EVIDENCE ACQUISITION: The National Library of Medicine Database was searched for relevant articles published between 2006 and 2015. Each article's title, abstract and text were reviewed for their appropriateness and their relevance. 57 articles were eligible for the review. EVIDENCE SYNTHESIS: In the elderly and frail, alpha1-antagonists should be used with caution given the risk of orthostatic hypotension and consequent falls, cause of significant morbidity in the elderly. 5ARIs present a good safety profile. Anticholinergics must also be prescribed with caution, given the risk of aggravating symptoms of dementia due to a central blockage of cholinergic neuronal pathways. Prostatic urethral lift is a medical device with low morbidity and valid functional results, which appear to endure over time. Prostatic artery embolization is demonstrating good results with minimal complication rates. Laser prostate vaporization or enucleation is also safe in elderly men and in those receiving anticoagulation therapy, due to its excellent hemostatic effect on prostatic tissue. CONCLUSIONS: Urologists should be familiar with the safety and efficacy profile of medical and surgical therapy in the elderly population, given the inevitable increase in older patients which we will observe in the near future. PMID- 27681494 TI - Influenza in the Emergency Department. PMID- 27681495 TI - Coexistent Panspinal Subdural Abscess and Isolated Leptomeningeal Myeloma Relapse Presenting as Rapid-Onset Paraparesis. PMID- 27681496 TI - Reperfusion treatment delays amongst patients with painless ST segment elevation myocardial infarction. AB - OBJECTIVE: Early reperfusion therapy in the treatment of ST segment elevation myocardial infarction (STEMI) patients can improve outcomes. Silent myocardial infarction is associated with poor prognosis, but little is known about its effect on treatment delays. We aimed to characterize STEMI patients presenting without complaints of pain to the emergency departments (EDs) in Singapore. METHODS: Retrospective data were requested from the Singapore Myocardial Infarction Registry (SMIR), a national level registry in Singapore. Painless STEMI was defined as the absence of pain (chest, back, shoulder, jaw, and epigastric pain) during ED presentation. The primary outcome was door-to-balloon (D2B) time, defined as the earliest time a patient arrived in the ED to balloon inflation. Secondary outcomes were 1-month and 1-year mortality and occurrence of adverse events. RESULTS: From January 2010 to December 2012, the SMIR collected 6412 cases; 10.9% of patients presented without any pain. These patients were older (median age =75 v. 58 years old), more likely to be females (39.9% v. 16.1%), Chinese (74.9% v. 62.7%), obese (median body mass index [BMI] =24.5 v. 22.1), and with history of hypertension (71.1% v. 54.6%), diabetes mellitus (48.6% v. 37.0%), and acute myocardial infarction (20.0% v. 12.3%). They had a longer median D2B (80.5 v. 63 minutes, p<0.001) and a higher occurrence of 30-day (38.4% v. 5.7%) and 1-year mortality rates (47.3% v. 8.5%). CONCLUSION: A small proportion of STEMI patients presented without any pain to the ED. They tended to have a higher D2B and risks of mortality. Targeted effort is required to improve diagnostic and treatment efficiency in this group. PMID- 27681498 TI - Development of a Microflow System for In-Cell Footprinting Coupled with Mass Spectrometry. AB - Fast photochemical oxidation of proteins (FPOP) has become a valuable tool for protein structural characterization. The method has recently been demonstrated to oxidatively modify solvent-accessible sites of proteins inside live cells (IC FPOP). However, the flow system used for in vitro analysis is not well-suited for IC-FPOP as a number of factors can lead to cell aggregation, causing inconsistent labeling and clogging. Here, we present an IC-FPOP flow system that centrally focuses the cells, ensuring consistent radiation exposure. Fluorescence imaging was used to analyze the effectiveness of the system in focusing the cells. Analysis shows the cells flowing individually through the center of the capillary with the buffer visible along the walls and with no aggregation or clogging observed. To ensure the flow system does not disturb oxidative modification, Vero cells were labeled using the flow system and analyzed by liquid chromatography mass spectrometry (LC-MS). The results demonstrate a 13-fold increase in the number of oxidized proteins and a 2 orders of magnitude increase in the dynamic range of the method. PMID- 27681497 TI - Development and Validation of a Food-Associated Olfactory Test (FAOT). AB - Olfactory tests are an important tool in human nutritional research for studying food preferences, yet comprehensive tests dedicated solely to food odors are currently lacking. Therefore, within this study, an innovative food-associated olfactory test (FAOT) system was developed. The FAOT comprises 16 odorant pens that contain representative food odors relating to different macronutrient classes. The test underwent a sensory validation based on identification rate, intensity, hedonic value, and food association scores. The accuracy of the test was further compared to the accuracy of the established Sniffin' Sticks identification test. The identification rates and intensities of this new FAOT were found to be comparable to the Sniffin' Sticks olfactory identification test. The odorant pens were also assessed chemo-analytically and were found to be chemically stable for at least 24 weeks. Overall, this new identification test for use in assessing olfaction in a food-associated context is valid both in terms of its use in sensory perception studies and its chemical stability. The FOAT is particularly suited to examinations of the sense of smell regarding food odors. PMID- 27681500 TI - Pillarplexes: A Metal-Organic Class of Supramolecular Hosts. AB - Novel octanuclear NHC complexes of gold(I) and silver(I) form metallocavitand structures with very defined tubular cavities and are able to selectively host linear molecules, exemplarily demonstrating 1,8-diaminooctane as a model guest molecule. The solubility of the host-compounds is easily adjusted by simple anion exchange reactions so that the compounds can be made soluble in water wherein they exhibit a high longtime stability. The gold(I) complex is emissive in aqueous solutions, which enables a determination of the binding constant to the diamine via luminescence quenching. The host-guest interaction was further investigated by isothermal titration calorimetry, NMR spectroscopy, and X-ray crystallography. PMID- 27681499 TI - Highly Sensitive Protein Detection Based on Smart Hybrid Nanocomposite-Controlled Switch of DNA Polymerase Activity. AB - In this work, we have successfully designed a smart and flexible signal amplification method based on a newly synthesized hybrid nanocomposite with switchable enzyme activity for specific and sensitive protein detection. The smart hybrid nanocomposite synthesized here is initially loaded with quenched fluorophore and a unique aptamer-inhibited DNA polymerase. It then undergoes target protein-triggered release of the fluorophore and activation of the DNA polymerase, which can thereby promote multiple catalytic reactions and recycled use of the target protein, resulting in the generation of highly amplified signals. Therefore, a small amount of target protein can lead to a large amount of signal without being consumed. In addition, the programmable control of DNA polymerase activity may effectively reduce background signal and avoid false positive results, which may further facilitate an efficient detection of small amounts of protein. By taking the detection of human stress-induced phosphoprotein 1 (STIP1) as an example, the excellent performance of this method has been verified. Furthermore, the proposed method has been used to analyze serum STIP1 from patients of ovarian cancer, showing promising application in clinical practice. PMID- 27681501 TI - Corrigendum to "Incretin-based drugs and risk of acute pancreatitis: A nested case control study within a healthcare database" [Diabetes Res. Clin. Pract. 108 (2) (2015) 243-249]. PMID- 27681502 TI - Deficiency of fat-soluble vitamins in chronic pancreatitis: A systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Chronic pancreatitis (CP) patients are at risk for fat soluble vitamins (A, D, E, K) deficiency, but available studies are small and heterogeneous. We conducted a systematic review and meta-analysis to determine the prevalence of fat-soluble vitamins deficiency in CP patients. METHODS: Medline was searched up to January 2016 for case series and case-control studies reporting prevalence of fat-soluble vitamin deficiency in CP patients. The prevalent deficiency rate was pooled for included studies, and deficiency rate between CP and controls, with relative odds ratio (OR) and 95% confidence interval (CI) calculated for case-control studies. RESULTS: Twelve studies including 548 patients included. With a random-effect model, the pooled prevalence rate of vitamin A, D and E deficiency were 16.8% (95%CI 6.9-35.7), 57.6% (95%CI 43.9-70.4) and 29.2% (95%CI 8.6-64.5) respectively, with considerable heterogeneity (I2 = 75%, 87.1% and 92%). Only one study evaluated vitamin K deficiency. The pooled OR for vitamin D deficiency in CP cases compared with controls was 1.17 (95% CI 0.77-1.78). Sensitivity analyses showed lower prevalence of vitamin A and E, and higher prevalence of vitamin D deficiency in high-quality studies. The rate of pancreatic exocrine insufficiency did not seem affect the deficiency rates, while the use of different cut-offs influences results and heterogeneity for vitamin E, but not A. CONCLUSIONS: Fat-soluble vitamins deficiency is frequent in CP patients, with considerable heterogeneity. There is, however, no apparent increased risk of vitamin D deficiency in CP compared to controls. Larger, high-quality studies are necessary to better estimate the prevalence of fat-soluble vitamins deficiency, including vitamin K. PMID- 27681504 TI - Factors and outcomes associated with pancreatic duct disruption in patients with acute necrotizing pancreatitis. AB - BACKGROUND AND AIMS: Acute necrotizing pancreatitis (ANP) can affect main pancreatic duct (MPD) as well as parenchyma. However, the incidence and outcomes of MPD disruption has not been well studied in the setting of ANP. METHODS: This retrospective study investigated 84 of 465 patients with ANP who underwent magnetic resonance cholangiopancreatography and/or endoscopic retrograde cholangiopancreatography. The MPD disruption group was subclassified into complete and partial disruption. RESULTS: MPD disruption was documented in 38% (32/84) of the ANP patients. Extensive necrosis, enlarging/refractory pancreatic fluid collections (PFCs), persistence of amylase-rich output from percutaneous drainage, and amylase-rich ascites/pleural effusion were more frequently associated with MPD disruption. Hospital stay was prolonged (mean 55 vs. 29 days) and recurrence of PFCs (41% vs. 14%) was more frequent in the MPD disruption group, although mortality did not differ between ANP patients with and without MPD disruption. Subgroup analysis between complete disruption (n = 14) and partial disruption (n = 18) revealed a more frequent association of extensive necrosis and full-thickness glandular necrosis with complete disruption. The success rate of endoscopic transpapillary pancreatic stenting across the stricture site was lower in complete disruption (20% vs. 92%). Patients with complete MPD disruption also showed a high rate of PFC recurrence (71% vs. 17%) and required surgery more often (43% vs. 6%). CONCLUSIONS: MPD disruption is not uncommon in patients with ANP with clinical suspicion on ductal disruption. Associated MPD disruption may influence morbidity, but not mortality of patients with ANP. Complete MPD disruption is often treated by surgery, whereas partial MPD disruption can be managed successfully with endoscopic transpapillary stenting and/or transmural drainage. Further prospective studies are needed to study these items. PMID- 27681503 TI - Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature. AB - BACKGROUND: The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management. METHODS: A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015. RESULTS: MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five year survival after surgical resection of a malignant MCN is approximately 60%. CONCLUSIONS: Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs. PMID- 27681505 TI - New Algorithm and Software (BNOmics) for Inferring and Visualizing Bayesian Networks from Heterogeneous Big Biological and Genetic Data. AB - Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology-type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types-single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc. PMID- 27681506 TI - Increased interleukin-35 expression in tumor-infiltrating lymphocytes correlates with poor prognosis in patients with breast cancer. AB - Interleukin-35 (IL-35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL-35 expression in tumor-infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL-35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme-linked immunosorbent assay. IL-35 expression in the tissue specimens was analyzed by immunohistochemistry. It was shown that 39.1%, 43.6% and 17.3% of the 110 patients were absent, weak, and strong IL-35 expression in the TILs, respectively. Strong IL-35 expression in TILs was significantly associated with age >50years, tumor size >2cm, TNM stage III, and negative ER (All P<0.05). Patients with elevated IL-35 expression in TILs had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with weak or no IL-35 expression (All P<0.05). High plasma IL-35 levels were significantly associated with TNM stage III and lymph node metastasis (All P<0.05). Plasma IL-35 level and IL-35 expression in the TILs of breast cancer tissues may be a valuable biomarker in the development and prognosis of IDC. PMID- 27681507 TI - Radiofrequency Catheter Ablation Improves the Quality of Life Measured with a Short Form-36 Questionnaire in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The main purpose of performing radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients is to improve the quality of life (QoL) and alleviate AF-related symptoms. We aimed to determine the qualitative and quantitative effects of RFCA on the QoL in AF patients. METHODS: We performed a systemic review and meta-analysis using a random effects model. We searched for the studies that reported the physical component summary score (PCS) and mental component summary score (MCS) of the short form-36, a validated system to assess and quantify the QoL, before and after RFCA in AF patients. PCS and MCS are T scores with a mean of 50 and standard deviation of 10. RESULTS: Of the 470 studies identified through systematic search, we included 13 studies for pre-RFCA vs. the post-RFCA analysis and 5 studies for treatment success vs. AF recurrence analyses. In the pre-RFCA vs. post-RFCA analysis, RFCA was associated with a significant increase in both the PCS (weighted mean difference [WMD] = 6.33 [4.81 7.84]; p < 0.001) and MCS (WMD = 7.80 [6.15-9.44]; p < 0.001). The DeltaPCS (post RFCA PCS-pre-RFCA PCS) and DeltaMCS values were used for the treatment success vs. AF recurrence analysis. Patients with successful ablation had a higher DeltaPCS (WMD = 7.46 [4.44-10.49]; p < 0.001) and DeltaMCS (WMD = 7.59 [4.94 10.24]; p < 0.001). CONCLUSIONS: RFCA is associated with a significant increase in the PCS and MCS in AF patients. Patients without AF recurrence after RFCA had a better improvement in the PCS and MCS than patients who had AF recurrence. PMID- 27681509 TI - Engaging Patients and Families Beyond the Point of Care: An Emergent Model. PMID- 27681510 TI - Nurse Executives Wearing 2 Hats as Strategic Leaders. AB - Disruptions in healthcare are challenging nurse leaders to develop innovative care delivery strategies and make the space for nursing practice innovation at the point of care or service. These functions are interdependent and require strong nursing leadership to challenge the status quo thinking of our colleagues. The ultimate goal of disruptive innovation is to ensure that care innovations are aligned with changing consumer and payer expectations, while ensuring safety, reliability, and cost-effectiveness. PMID- 27681508 TI - Alternative Splice Variants Modulates Dominant-Negative Function of Helios in T Cell Leukemia. AB - The molecular defects which lead to multistep incidences of human T-cell leukemia have yet to be identified. The DNA-binding protein Helios (known as IKZF2), a member of the Ikaros family of Kruppel-like zinc-finger proteins, functions pivotally in T-cell differentiation and activation. In this study, we identify three novel short Helios splice variants which are T-cell leukemic specific, and demonstrate their dominant-negative function. We then test the cellular localization of distinct Helios isoforms, as well as their capability to form heterodimer with Ikaros, and the association with complexes comprising histone deacetylase (HDAC). In addition, the ectopic expression of T-cell leukemic Helios isoforms interferes with T-cell proliferation and apoptosis. The gene expression profiling and pathway analysis indicated the enrichment of signaling pathways essential for gene expression, translation, cell cycle checkpoint, and response to DNA damage stimulus. These data indicate the molecular function of Helios to be involved in the leukemogenesis and phenotype of T-cell leukemia, and also reveal Helios deregulation as a novel marker for T-cell leukemia. PMID- 27681511 TI - A Qualitative Study of Factors Facilitating Clinical Nurse Engagement in Emergency Department Catheter-Associated Urinary Tract Infection Prevention. AB - OBJECTIVE: The aim of this study was to explore the actions of nurse leaders that facilitated clinical nurses' active involvement in emergency department (ED) catheter-associated urinary tract infection (CAUTI) prevention programs. BACKGROUND: Hospitals face increasing financial pressures to reduce CAUTI. Urinary catheters, often inserted in the ED, expose patients to CAUTI risk. Nurses are the principal champions of ED CAUTI prevention programs. METHODS: This was a qualitative analysis from a multisite, comparative case study project. A total of 52 interviews and 9 focus groups were analyzed across 6 enrolled EDs. Using a conventional content analysis, members of the research team coded data and developed site summaries to describe themes that had emerged across transcripts. Subsequently, all codes and site summaries were reviewed to identify the actions of nurse leaders that facilitated clinical nurses' engagement in CAUTI prevention efforts. RESULTS: Nurse leaders were the principal champions of CAUTI prevention programs and successfully engaged clinical nurses in CAUTI prevention efforts by (1) reframing urinary catheters as a source of potential patient harm; (2) empowering clinical nurses to identify and address CAUTI improvement opportunities; (3) fostering a culture of teamwork, which facilitated interdisciplinary communication around urinary catheter appropriateness and alternatives; and (4) holding clinical nurses accountable for CAUTI process and outcome measures. CONCLUSIONS: The prevention of CAUTI is an important opportunity for nurse leaders to engage clinical nurses in meaningful improvement efforts. Clinical nurses are best positioned to examine urinary catheter insertion workflow and to suggest improvements in avoiding use and improving placement and maintenance. To engage clinical nurses in CAUTI prevention, nurse leaders should focus on how urinary catheters expose patients to potential harm, involve nurses in designing and implementing practice changes, and provide local data to show the impact of nursing practices on patient outcomes. PMID- 27681512 TI - Evidence-Based Practice and Job-Related Nurse Outcomes at Magnet(r)-Aspiring, Magnet-Conforming, and Non-Magnet University Hospitals in Finland: A Comparison Study. AB - OBJECTIVE: The aim of this study was to compare nurses' evidence-based practice (EBP) beliefs, EBP knowledge, and nurse workforce outcomes between Magnet(r) aspiring, Magnet-conforming, and non-Magnet university hospitals in Finland. BACKGROUND: The effect of Magnet designation on EBP and nursing workforce outcomes is well studied where Magnet hospitals exist. Less is known about it in countries where hospitals are embarking upon the initial Magnet journey. METHODS: A descriptive cross-sectional national survey was conducted at Finnish university hospitals with a convenience sample (n = 943) of practicing nurses. Data were analyzed using descriptive and inferential statistics. RESULTS: Although nurses' EBP beliefs were favorable and they were satisfied with their jobs, they reported low levels of EBP knowledge. Statistically significant differences were found between hospitals' Magnet journey status and nurses' levels of perceived EBP knowledge. CONCLUSIONS: Although nurses believed in the value of EBP and were satisfied with and likely to stay in their jobs and in nursing, they lacked the EBP knowledge required for integrating best evidence into clinical care. PMID- 27681513 TI - Advanced Practice Providers' Perceptions of Patient Workload: Results of a Multi Institutional Survey. AB - OBJECTIVE: This study examines data collected from a survey of advanced practice providers' (APPs') perceptions of reasonable versus actual APP-to-patient ratios and other factors that affect workload burden in both inpatient and outpatient clinical settings. BACKGROUND: Advanced practice providers provide accessible, cost-effective, and quality care in a growing number of specialty practices across multiple patient care settings. They are caring for higher volumes of patients and assuming more responsibilities while continuing to navigate highly complex healthcare systems. Limited evidence or benchmark data exist that would assist in determining optimal workload and staffing models that include APPs. METHODS: A group of advanced practice leaders developed and distributed a 43 question survey of workload factors to a highly diverse APP workforce. RESULTS: There were 1466 APPs across 37 areas of practice who responded to the survey distributed in 14 separate organizations. The perceived reasonable workload was lower than the actual workload for 22 specialty practice areas. The analysis included years of experience as an APP, work hours, on-call commitment, nonclinical responsibilities, and time spent in documentation, direct patient care, and performing procedures. CONCLUSIONS: There is a consensus among APPs, within their practice area, about what constitutes a reasonable patient assignment, despite the variability in APP experience, organizational culture, processes, and patient acuity. PMID- 27681514 TI - Beyond Magnet(r) Designation: Perspectives From Nurse Managers on Factors of Sustainability and High-Performance Programming. AB - OBJECTIVE: The aim of this study was to identify patterns of high-performing behaviors and nurse manager perceptions of the factors of Magnet(r) sustainability at a multidesignated Magnet organization. BACKGROUND: The Magnet program recognizes exemplary professional nursing practice and is challenging to achieve and sustain. Only 10% (n = 42) of Magnet hospitals sustained designation for 12 years or longer. This study explored the perspectives of Magnet nurse managers regarding high-performing teams and the sustainability of Magnet designation. METHODS: A qualitative study of nurse managers was conducted at 1 multidesignated Magnet organization (n = 13). Interview responses were analyzed using pattern recognition of Magnet model domains and characteristics of high performing teams and then related to factors of Magnet sustainability. RESULTS: Transformational leadership is both an essential factor for sustainability and a potential barrier to sustainability of Magnet designation. CONCLUSIONS: Transformational nursing leaders lead high-performing teams and should be in place at all levels as an essential factor in sustaining Magnet redesignation. PMID- 27681515 TI - Impact of Standardized New Medication Education Program on Postdischarge Patients' Knowledge and Satisfaction. AB - This study, implemented on 2 medical-surgical units, evaluated the impact of a standardized, evidence-based new medication education program. Outcomes evaluated included patient postdischarge knowledge of new medication purpose and side effects, patient satisfaction with new medication, and Medicare reimbursement earn-back potential. As a result, knowledge scores for new medication purpose and side effects were high post intervention. Patient satisfaction with new medication education increased. Value-based purchasing reimbursement earn-back potential improved. PMID- 27681516 TI - Nursing Peer Review Perceptions and Practices: A Survey of Chief Nurse Executives. AB - OBJECTIVE: This study sought to understand chief nurse executive perceptions of nursing peer review (NPR) and current NPR practices in their organizations to provide insights and recommendations for the path forward to a robust NPR approach nationally. BACKGROUND: Nursing peer review is a key component of professional nursing practice focused on self-regulation and improving quality and safety. Despite its known benefits, NPR is not broadly disseminated, and how it is currently used and perceived is not well understood. METHODS: A causal comparison study design was used. A 25-question, Web-based survey was administered to collect data variables. RESULTS: Chief nurse executives perceived NPR as important in improving quality and safety; however, its prevalence was low. Chief nurse executives also reported NPR practices not aligned with the American Nurses Association (ANA) NPR guidelines. CONCLUSIONS: Results suggest that knowledge gaps exist regarding NPR's purpose, outcomes, and alignment with the ANA peer review guidelines. Interventions are needed to address these gaps to further advance NPR adoption nationally. PMID- 27681518 TI - Estrogen receptor alpha gene ( ESR1) polymorphism can contribute to clinical findings in systemic lupus erythematosus patients. AB - Background Estrogens have a modulatory effect on several immune responses, many of which are correlated to autoimmune diseases. Estrogens act through binding to their receptors, and an overexpression of these receptors has been identified in patients with different autoimmune diseases. Here we analyzed the association of a putative functional genetic variant in the main estrogen receptor (ERalpha) gene ( ESR1), and the susceptibility to clinical findings and severity of SLE. Methods A total of 426 individuals (266 healthy controls and 160 SLE patients) were genotyped for the polymorphism rs2234693 in the ESR1 gene. Allele and genotype frequencies were calculated and analyzed between cases and controls using Unphased software. Results The SNP rs2234693 was not associated with SLE per se but the minor allele rs2234693-C was correlated with the presence of nephritis and discoid skin rash. On the other hand, the rs2234693-CC genotype was correlated with the absence of arthritis as well as anti-ANA and anti-RNP autoantibodies. The comprehensive clinical analysis of these patients revealed a more severe status of the disease, characterized by a younger age of onset and higher number of organs involved when compared to European populations. Conclusions Minor allele rs2234693-C was associated with renal and cutaneous involvement, as well as the absence of arthritis, anti-ANA and anti-RNP autoantibodies. PMID- 27681519 TI - Patients Presenting to the Emergency Unit with Gynaecological Lower Abdominal Pain, with and without Pathological Clinical Findings - Service Utilisation, Pain History, Implications. AB - Introduction: Few studies have evaluated the utilisation of emergency gynaecological services, although lower abdominal pain (LAP) is one of the most common symptoms prompting emergency presentation. Although such pain may be caused by potentially life-threatening gynaecological diseases, very often no clinical cause is found. The aim of this study was to describe the characteristics of emergency presentations in order to enable quicker identification of real emergencies in routine clinical practice. Materials and Methods: Standardised, so-called first aid cards of 1066 consecutive patients with LAP presenting acutely to one emergency unit were analysed in this retrospective, cross-sectional study. Results: Over one third of cases did not constitute actual medical emergencies on objective criteria, with investigations yielding "no pathological findings". Parameters were identified that more often lead to hospital admission, e.g. palpation of a mass/resistance or at least one pathological ultrasound finding. In addition, it was found that symptoms of longer duration (average 8 days), and not only acute LAP, were also often experienced by patients as emergencies. Conclusion: A diagnosis of "no pathological findings", which was common in our study, suggests a subjective experience of an emergency from the patient's point of view, although the possibility of unrecognised pathology has to be borne in mind. Apart from functional disorders, the origins of symptoms may include psychosomatic causes and psychosocial problems, which cannot be further defined in the emergency care setting. Also, the phenomenon of increased utilisation of emergency services parallel to the assumed opening hours of routine outpatient care facilities must be seen in a critical light. PMID- 27681517 TI - Applied statistical training to strengthen analysis and health research capacity in Rwanda. AB - BACKGROUND: To guide efficient investment of limited health resources in sub Saharan Africa, local researchers need to be involved in, and guide, health system and policy research. While extensive survey and census data are available to health researchers and program officers in resource-limited countries, local involvement and leadership in research is limited due to inadequate experience, lack of dedicated research time and weak interagency connections, among other challenges. Many research-strengthening initiatives host prolonged fellowships out-of-country, yet their approaches have not been evaluated for effectiveness in involvement and development of local leadership in research. METHODS: We developed, implemented and evaluated a multi-month, deliverable-driven, survey analysis training based in Rwanda to strengthen skills of five local research leaders, 15 statisticians, and a PhD candidate. Research leaders applied with a specific research question relevant to country challenges and committed to leading an analysis to publication. Statisticians with prerequisite statistical training and experience with a statistical software applied to participate in class-based trainings and complete an assigned analysis. Both statisticians and research leaders were provided ongoing in-country mentoring for analysis and manuscript writing. RESULTS: Participants reported a high level of skill, knowledge and collaborator development from class-based trainings and out-of class mentorship that were sustained 1 year later. Five of six manuscripts were authored by multi-institution teams and submitted to international peer-reviewed scientific journals, and three-quarters of the participants mentored others in survey data analysis or conducted an additional survey analysis in the year following the training. CONCLUSIONS: Our model was effective in utilizing existing survey data and strengthening skills among full-time working professionals without disrupting ongoing work commitments and using few resources. Critical to our success were a transparent, robust application process and time limited training supplemented by ongoing, in-country mentoring toward manuscript deliverables that were led by Rwanda's health research leaders. PMID- 27681520 TI - Osteopathy for Endometriosis and Chronic Pelvic Pain - a Pilot Study. AB - Introduction: Pelvic pain is a common problem in gynaecological practice. It is often unclear whether definite causality exists between reported symptoms and objective clinical findings of the female genital tract, and medical or operative treatments do not always achieve long-term resolution of symptoms. Methods: This pilot study investigated 28 patients (age 20-65, median 36.5 years) from a gynaecology practice whose only clinical finding was painful pelvic floor muscle tightness. Following standardised gynaecological and physiotherapist examination, all patients received osteopathic treatment. Pain had been present for a median of 3 years (range 1 month to 20 years). 14 patients had previously confirmed endometriosis. Treatment success was evaluated on consultation with patients in person or in writing. Results: 22 of the 28 participants completed the treatment according to plan. Overall, 17 reported symptom improvement, while 10 of the 14 patients with endometriosis did. Conclusion: Osteopathy is well received by women with painful pelvic floor muscle tightness and appears to be an effective treatment option. PMID- 27681521 TI - Efficacy and Effects of Parenteral Pethidine or Meptazinol and Regional Analgesia for Pain Relief during Delivery. A Comparative Observational Study. AB - Background: Peripartum anesthesia may consist of parenteral opioids and/or regional analgesia. There is only limited data in the literature comparing both methods in daily obstetric practice. This observational study investigated the opioids pethidine and meptazinol as well as regional analgesics with regard to their administration, efficacy, side effects and subjective maternal satisfaction with therapy. The rates of secondary regional analgesia administration after administration of the respective opioid served as a means of evaluating treatment. Methods: This study collected data on pain management during vaginal delivery in a German university hospital over a twelve month period. Severity of pain was measured intrapartum using a numerical rating scale. Maternal, neonatal and delivery-related data were obtained postpartum from the clinical records and from the mothers using a questionnaire. Results: The study is based on data obtained from 449 deliveries. Pain relief achieved by the administration of pethidine and meptazinol was similarly low; maternal satisfaction with the respective therapy was high. Meptazinol was usually administered intravenously (83 % vs. 6 %; p < 0.001), repeatedly (27 % vs. 6 %; p < 0.001) and closer to the birth (1.9 +/- 2.7 h vs. 2.6 +/- 2.8 h; p < 0.05) compared to pethidine. Secondary regional analgesia was more common after the administration of pethidine (16 % vs. 8 %; p < 0.05). Regional analgesia resulted in greater pain relief compared to opioid therapy (78 % vs. 24 % after 30 min; p < 0.001) and was associated with longer times to delivery (7.6 +/- 2.5 h vs. 5.7 +/- 2.5 h; p < 0.001) and higher levels of maternal satisfaction with therapy (6.1 +/- 1.2 vs. 4.8 +/- 1.6 on a 7-point scale; p < 0.001). Conclusion: In daily clinical practice, meptazinol can be adapted more readily to changes during birth and requires less secondary analgesia. Regional neuraxial analgesia was found to be an efficacious and safe way of managing labor pain. PMID- 27681522 TI - Differences in the Frequency of Use of Epidural Analgesia between Immigrant Women of Turkish Origin and Non-Immigrant Women in Germany - Explanatory Approaches and Conclusions of a Qualitative Study. AB - Introduction: The starting point of this study was the considerably lower rate of epidural analgesia use among women of Turkish origin in Germany compared to non immigrant women in the German Research Foundation (DFG)-funded study entitled "Perinatal Health and Migration Berlin". The study aimed to identify possible differences in the women's attitudes towards epidural analgesia. Methods: Exploratory study with semi-structured interviews, interviews lasting 17 minutes on average were conducted with 19 women of Turkish origin and 11 non-immigrant women at a Berlin hospital. The interviews were subjected to a qualitative content analysis. Results: Immigrant women of Turkish origin in Germany more frequently ascribe meaning to the pain associated with vaginal delivery. They more frequently categorically reject the use of epidural analgesia, 1) for fear of long-term complications such as paralysis and back pain and 2) based on the view that vaginal delivery with epidural analgesia is not natural. Information on epidural analgesia is frequently obtained from a variety of sources from their social setting, in particular, by word of mouth. The women in both groups stated that they would take the decision to use epidural analgesia independent of their partner's opinion. Discussion: The differences in epidural analgesia use rates observed correspond to the women's attitudes. For the immigrant women of Turkish origin in Germany, the attitude towards using epidural analgesia is based in part on misinformation. In order to enable the women to make an informed decision, epidural analgesia could receive a stronger focus during childbirth courses. PMID- 27681523 TI - Knowledge of Emergency Contraceptive Pills among Hungarian Women Presenting for Induced Abortion or Seeking Emergency Contraception. AB - Aim: To compare the differences in contraceptive characteristics and the knowledge of emergency contraception (ECP) among women who used ECP after unprotected intercourse and those who sought an abortion. Methods: A questionnaire survey was conducted in a Hungarian university hospital among women for whom ECP was prescribed after unprotected intercourse (n = 940) as well as women who presented for the termination of pregnancy (n = 1592) between January 1, 2005 and November 20, 2006. Their knowledge of ECP and their experience with and attitudes toward ECP use were targeted. Results: The availability of ECP was well known (87.9 %), but it was still greatly underutilized: applied by only 13 of the 1592 women who resorted to abortion. Primarily, the ECP group consisted of those who experienced a condom failure significantly more often (odds ratio [OR] = 4.1), followed by those cases where ECP applications was a consequence of not using any kind of contraception (OR = 3.8). Fewer than one third (32 %) of the abortion seekers had previously used ECP, and only one fifth knew how to obtain it. Appropriate awareness of ECP was influenced by information obtained from health-care providers (adjusted odds ratio [AOR] = 3.93) or school education (AOR = 1.82). Conclusions: More thorough education is needed to provide a deeper knowledge of ECP use during contraceptive counseling for women seeking abortion, including those contraceptive mishaps where unintended pregnancy can be prevented by ECP. PMID- 27681525 TI - Quantitative assessment of washout in hepatocellular carcinoma using MRI. AB - BACKGROUND: Arterial hyperenhancement and washout on computed tomography and magnetic resonance imaging (MRI) are described by all major guidelines as specific criteria for non-invasive diagnosis of hepatocellular carcinoma (HCC). However, publications on the quantitative assessment of washout in MRI are lacking. Therefore, we evaluated a method for quantitatively measuring and defining washout in MRI in order to determine a cutoff value that allows objective HCC diagnosis. METHODS: We analyzed all patients who underwent liver transplantation for cirrhosis or liver resection for HCC at our institution between 2003 and 2014. Washout was quantitatively investigated by placing a 25 mm2 region of interest (ROI) over each nodule and two 25-mm2 ROIs over adjacent liver parenchyma. The percentage signal ratio (PSR = 100 * ratio of signal intensity of adjacent liver to that of the lesion) was calculated for each series in both groups. Accordingly, this quantitative measurement was compared to a qualitative approach. RESULTS: A total of 16 hypervascularized non-HCC nodules and 69 HCC nodules were identified. Interobserver reliability was reasonably good for the measurement of PSRs and readers showed a substantial agreement for the qualitative assessment. In the HCC group, the median PSR was 116.2 at equilibrium and 112.9 in the delayed phase. In the non-HCC group, the median PSR was 93.8 at equilibrium and 96.0 in the delayed phase. Receiver operating characteristic analysis indicated areas under the curve of 0.902 (p < 0.001) and 0.873 (p < 0.001) at equilibrium and in the delayed phase. PSR values of 102 at equilibrium and 101.5 in the delayed phase led to the highest Youden's index of 0.82 and 0.77, respectively. These PSR cutoffs yielded sensitivities of 82 and 77 %, respectively, with specificities of 100 %. The sensitivity for the qualitative assessment of washout was 88 and 93 % and the specificity was 48 and 56 %. For the classification of HCC, sensitivity yielded 95 and 97 % and specificity was 68 and 56 %, respectively. CONCLUSION: Quantitatively measuring HCC washout in MRI is easy and reproducible. It can objectify and support diagnosis of HCC. However, the quantitative measurement of washout can only serve as one of several components of HCC assessment. PMID- 27681526 TI - Associations among height, body mass index and intelligence from age 11 to age 78 years. AB - BACKGROUND: Intelligence is related to both height and body mass index (BMI) at various stages of life. Several studies have demonstrated longitudinal relationships between these measures, but none has established whether height and intelligence, or BMI and intelligence are linked from childhood through to older age. METHODS: We assessed the relations between these measures over an interval of up to 67 years using data from the 36-Day Sample, an initially-representative sample of Scottish people born in 1936, assessed at age 11 years (N = 6,291) and again at 77-78 years (N = 722). This paper focuses on the 423 participants (6.7 % of the original sample) who provided relevant data in late adulthood. RESULTS: Height and intelligence were significantly positively associated in childhood (beta = .23) and late adulthood (beta = .21-.29). Longitudinal correlations also showed that childhood intelligence predicted late-adulthood height (beta = .20), and childhood height predicted late-adulthood cognitive ability (beta = .12-.14). We observed no significant relationship between BMI and intelligence either in childhood or in late adulthood, nor any longitudinal association between the two in this sample. CONCLUSIONS: Our results on height and intelligence are the first to demonstrate that their relationship spans almost seven decades, from childhood through to late adulthood, and they call for further investigation into the mechanisms underlying this lifelong association. PMID- 27681527 TI - Do not snare rectal polyps. PMID- 27681524 TI - Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review. AB - BACKGROUND: Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. METHODOLOGY AND PRINCIPAL FINDINGS: A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1,557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. CONCLUSIONS: Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans. PMID- 27681528 TI - Sumatriptan Nasal Powder: A Review in Acute Treatment of Migraine. AB - Sumatriptan nasal powder delivered by a breath powered delivery device (ONZETRA(r) Xsail(r)) is indicated for the acute treatment of migraine with or without aura in adults. This narrative review discusses the clinical use of sumatriptan nasal powder in this population and summarizes its pharmacological properties. In migraineurs, sumatriptan nasal powder treatment was associated with significantly greater rates of pain relief than placebo from 0.5-2 h postdose after a single treatment in the phase 3 TARGET trial, with these benefits sustained at 24 and 48 h postdose. Compared with oral sumatriptan, sumatriptan nasal powder was associated with significantly faster pain relief during the first 30 min after treatment in the phase 3 COMPASS trial assessing the treatment of up to five migraines in adults and better pain relief and pain freedom from 15 min to 1.5 h postdose. However, there were no between-group differences in pain relief at subsequent timepoints up to 48 h postdose. Sumatriptan nasal powder was generally well tolerated, with the majority of adverse events administration-site related and mild or moderate in severity. In conclusion, sumatriptan nasal powder is an effective and generally well tolerated treatment of migraine. With its novel breath powered nasal delivery resulting in a faster onset of action than oral sumatriptan, sumatriptan nasal powder provides a useful new option for the acute treatment of migraine with and without aura in adults. PMID- 27681529 TI - Spanish experience on the design of radon surveys based on the use of geogenic information. AB - One of the requirements of the recently approved EU-BSS (European Basic Safety Standards Directive, EURATOM, 2013) is the design and implementation of national radon action plans in the member states (Annex XVIII). Such plans require radon surveys. The analysis of indoor radon data is supported by the existing knowledge about geogenic radiation. With this aim, we used the terrestrial gamma dose rate data from the MARNA project. In addition, we considered other criterion regarding the surface of Spain, population, permeability of rocks, uranium and radium contain in soils because currently no data are available related to soil radon gas concentration and permeability in Spain. Given that, a Spanish radon map was produced which will be part of the European Indoor Radon Map and a component of the European Atlas of Natural Radiation. The map indicates geographical areas with high probability of finding high indoor radon concentrations. This information will support legislation regarding prevention of radon entry both in dwellings and workplaces. In addition, the map will serve as a tool for the development of strategies at all levels: individual dwellings, local, regional and national administration. PMID- 27681530 TI - [Osteoporosis detection using cone-beam computed tomography]. AB - BACKGROUND: Osteoporosis is still underdiagnosed in Germany. OBJECTIVES: Is it possible to detect osteoporosis on the basis of a cone-beam computed tomography image of the mandible and several measuring methods? MATERIALS AND METHODS: Sixteen cone-beam computed tomography (CBCT) images from patients of the dental clinic at the University of Ulm were reinvestigated. When the CBCT images were processed the subjects were at least 55 years old, and the mandible was completely mapped on the image. Furthermore, a dual-energy X-ray absorptiometry scan or a CT bone mineral density test was required for every subject. The subjects were divided into an osteoporosis group and a control group. The computed tomography mental index (CTMI), the computed tomography mandibular index superior (CTI[S]) and the computed tomography mandibular index inferior (CTI[I]) were deployed for comparison of the groups. In the first instance a comparison of the osteoporosis and control groups was made for both male and female subjects. Subsequently, only the images of the female subjects were compared to each other. RESULTS: A possibility for osteoporosis can be expressed at CTMI values located < 3.0 mm. As well for CTI(S) < 0.18 and CTI(I) < 0.23. There arises a 66.7 % sensitivity and 70 % specificity for the mixed subject group and an 80 % sensitivity and 57.1 % specificity for the female subject group for CTMI and CTI(S). Furthermore, there are 50.0 % sensitivity and 70 % specificity for the mixed subject group and 60.0 % sensitivity and 57.1 % specificity for the female subject group for the CTI(I). CONCLUSION: CTMI, CTI(S) and CTI(I) are only suitable for osteoporosis detection to a limited extent. PMID- 27681531 TI - Hyperfocusing as a dimension of adult attention deficit hyperactivity disorder. AB - Patients with Attention Deficit Hyperactivity Disorder (ADHD) suffer not only from inability to focus but also from inability to shift attention for events that trigger their interests. This phenomenon is called "hyperfocusing". Previous literature about hyperfocusing is scarce and relies mainly on case reports. The study aimed to investigate and compare the severity of hyperfocusing in adult ADHD with and without psycho-stimulant use. ADHD (DSM-IV-TR) patients either psycho-stimulant naive (n=53) or on psycho-stimulants (n=79) from two ADHD clinics were recruited. The control group (n=65) consisted of healthy university students. A socio-demographic form, the Beck Depression Inventory, the Wender Utah Rating Scale, the Adult ADHD Self- Report Scale and the Hyperfocusing Scale were applied to the participants. There was no difference between total Hyperfocusing Scale and Adult ADHD Self- Report Scale scores of two patient groups, but both have higher scores than controls (p<0.001). Hyperfocusing is higher in adult ADHD and there was no difference between stimulant-naive patients or patients on stimulants. Hyperfocusing can be defined as a separate dimension of adult ADHD. PMID- 27681532 TI - Skin sensitization risk assessment: Considering available data for weight of evidence assessments. PMID- 27681533 TI - Referral Patterns as a Contextual Variable in Pediatric Brain Injury: A Retrospective Analysis. AB - Purpose: Access to speech-language pathology (SLP) services is a critical variable in the rehabilitation of pediatric brain injury. In this study, we examined patterns of SLP referral and factors affecting referral during the acute period following brain injury in 2 large pediatric specialty hospitals. Method: In a retrospective, cohort chart review study, data collection focused on referrals made during the acute period using International Classification of Diseases, Ninth Revision, Clinical Modification codes for primary diagnoses of brain injury between 2007 and 2014 (Centers for Disease Control and Prevention [CDC], 2014). A total of 200 charts were reviewed. Data extraction included demographic and injury-related variables, referral for rehabilitation across disciplines, and plans of care following assessment. Results: Samples for both facilities were similar except for primary mechanism of traumatic brain injuries and severity. SLP referral rate at Hospital 1 was 36% and only 2% at Hospital 2. Regression revealed that individuals were less likely to receive an SLP referral if injury severity was classified as unknown or mild or if they were younger in age. Conclusion: SLP referral rates in the early acute period for children with brain injury were poor, creating a barrier to rehabilitation. This not only limits access to SLP services, but also may have broader and long-term impact. PMID- 27681534 TI - Preparation of chitosan-coated liposomes as a novel carrier system for the antiviral drug Triazavirin. AB - Novel method for the coating of positively charged liposomes with modified chitosan was elaborated. Liposomes were prepared by stepwise extrusion through inorganic membranes (Anotop) of 0.2 and 0.1 MUm pore sizes. Chitosan derivatives were synthesized via the Ugi multicomponent reaction. Several series of liposomal compositions were produced and their properties were compared in terms of particle size, polydispersity index (PDI), zeta potential and stability. The effect of various additives was investigated and the optimal composition of the lipid film was determined. The addition of the uncharged fatty esters allowed the diameter of the liposomes obtained by extrusion to be reduced to 145-150 nm with a PDI of 0.13-0.15. The prepared liposomes were loaded with the novel antiviral drug Triazavirin and used to determine the release profile. Triazavirin was included into liposome layer as a salt with biocompatible choline derivatives of limiting fatty acids. The appropriate lipid composition was used for the preparation of a larger quantity of liposomes coated by modified chitosan. It was shown that an appropriate combination of liposomes and polysaccharide layer potentially extended colloidal stability by up to 3 months and exhibited broad functional capabilities for surface modification. PMID- 27681537 TI - Inferior Vena Cava Filters in Trauma Patients-For Whom the Benefit Tolls? PMID- 27681536 TI - Dynamic Evaluation of the Cervical Spine and the Spinal Cord of Symptomatic Patients Using a Kinetic Magnetic Resonance Imaging Technique. AB - PURPOSE: The purpose of this study was to examine the movement of the spinal cord and its relationship to the spinal canal in patients with mild spondylosis using kinetic magnetic resonance imaging (kMRI). METHODS: Weight-bearing, multiposition kMRI was performed on symptomatic patients through a full range of flexion extension. A total of 52 study patients were selected based on the C2-C7 Cobb angle of sagittal alignment: lordotic (from 30 to 45 degrees). We evaluated dynamic changes in different parameters from flexion-extension: spinal canal diameter (CD), spinal cord diameter (SCD), space available for the cord, anterior space available for the cord (ASAC), posterior space available for the cord (PSAC), average distance between the anterior canal and the cord (d-value), and global angle for the spinal canal and cord. RESULTS: The CD tended to decrease from flexion to extension from C3/C4 to C6/C7, however, there were no significant differences at the proximal and distal levels, C2/C3 and C7/T1. There were no significant differences of SCD between different postures. The SCD tended to decrease from C2/C3 to C7/T1. The ASAC followed the same pattern as CD-values. The ASAC was narrowest at C4/C5 and C5/C6. The PSAC tended to increase from C2/C3 to C7/T1. The spinal cord shifted anteriorly with extension and posteriorly with flexion. In addition, the spinal cord maintained its curve with the movement. CONCLUSIONS: The kinematics of spinal cord motion may be associated with the pathogenesis of cervical spondylotic myelopathy. However, the spinal cord maintains its curve with position changes. Consequently, different motions of the cervical spine may affect spinal cord migration and cause changes in ASAC and PSAC. PMID- 27681535 TI - Posterior or Single-stage Combined Anterior and Posterior Approach Decompression for Treating Complex Cervical Spondylotic Myelopathy Coincident Multilevel Anterior and Posterior Compression. AB - STUDY DESIGN: A single-center, retrospective, longitudinal matched cohort clinical study of prospectively collected outcomes. OBJECTIVE: To compare retrospectively the clinical outcomes and complications of the posterior approach laminoplasty and single-stage anterior approach laminoplasty combined with anterior cervical corpectomy and fusion and anterior cervical discectomy and fusion for treating patients with cervical spondylotic myelopathy coincident multilevel anterior and posterior compression, known as complex cervical spondylotic myelopathy (cCSM) here. SUMMARY OF BACKGROUND DATA: The optimal surgical management of this type of cCSM remains controversial. METHODS: Sixty seven patients with multilevel cCSM underwent decompression surgery from 1996 to 2007. Among these patients, 31 underwent a single-stage combined approach with decompression (combined approach group) and 36 underwent laminoplasty for posterior approach (posterior approach group). Average operative duration, operative estimated blood loss, surgical costs, and cervical alignment were measured. RESULTS: Average operative duration, operative estimated blood loss, and surgical costs were significantly lower in the posterior approach group than those in the combined approach group (P<0.001). Visual analog scale and modified Japanese Orthopedic Association scale were insignificantly different at each data collection period (P>0.05). No statistical difference was observed in the preoperative Cobb angle (P>0.05), whereas a significant statistical difference was observed for the postoperative Cobb angle (P<0.05) and variation of Cobb angle (P<0.05) between the 2 groups. The surgical incidences of complications were 22.2% and 48.4% in the posterior and combined approach groups (P<0.05), respectively. CONCLUSIONS: For treating multilevel cCSM, both the posterior approach laminoplasty and single-stage combined approach led to significant neurological improvement and pain reduction in the majority of patients. Both approaches showed similar results in terms of decompression and neurological improvement. The posterior approach was superior to the combined approach in terms of surgical costs, surgical time, blood loss, and complication rate. PMID- 27681538 TI - Medical students' learning orientation regarding interracial interactions affects preparedness to care for minority patients: a report from Medical Student CHANGES. AB - BACKGROUND: There is a paucity of evidence on how to train medical students to provide equitable, high quality care to racial and ethnic minority patients. We test the hypothesis that medical schools' ability to foster a learning orientation toward interracial interactions (i.e., that students can improve their ability to successfully interact with people of another race and learn from their mistakes), will contribute to white medical students' readiness to care for racial minority patients. We then test the hypothesis that white medical students who perceive their medical school environment as supporting a learning orientation will benefit more from disparities training. METHODS: Prospective observational study involving web-based questionnaires administered during first (2010) and last (2014) semesters of medical school to 2394 white medical students from a stratified, random sample of 49 U.S. medical schools. Analysis used data from students' last semester to build mixed effects hierarchical models in order to assess the effects of medical school interracial learning orientation, calculated at both the school and individual (student) level, on key dependent measures. RESULTS: School differences in learning orientation explained part of the school difference in readiness to care for minority patients. However, individual differences in learning orientation accounted for individual differences in readiness, even after controlling for school-level learning orientation. Individual differences in learning orientation significantly moderated the effect of disparities training on white students' readiness to care for minority patients. Specifically, white medical students who perceived a high level of learning orientation in their medical schools regarding interracial interactions benefited more from training to address disparities. CONCLUSIONS: Coursework aimed at reducing healthcare disparities and improving the care of racial minority patients was only effective when white medical students perceived their school as having a learning orientation toward interracial interactions. Results suggest that medical school faculty should present interracial encounters as opportunities to practice skills shown to reduce bias, and faculty and students should be encouraged to learn from one another about mistakes in interracial encounters. Future research should explore aspects of the medical school environment that contribute to an interracial learning orientation. PMID- 27681540 TI - Online inferential and textual processing by adolescents with attention deficit/hyperactivity disorder during reading comprehension: Evidence from a probing method. AB - INTRODUCTION: Previous studies have demonstrated that students with attention deficit/hyperactivity disorder (ADHD) struggle particularly with grasping the implicit, inferential level of narratives that is crucial for story comprehension. However, these studies used offline tasks (i.e., after story presentation), used indirect measurements (e.g., identifying main ideas), and/or yielded inconclusive results using think-aloud techniques. Moreover, most studies were conducted with preschool or elementary school children with ADHD, using listening or televised story comprehension. In this study, we were interested in examining the spontaneous, immediate activation and/or suppression of forward predictive inferences, backward-explanatory inferences, and inference-evoking textual information, as they occur online during reading comprehension by adolescents with ADHD. METHOD: Participants with and without ADHD read short narrative texts, each of which included a predictive sentence, a bridging sentence that referred back to the predictive sentence via actualization of the predicted event, and two intervening sentences positioned between the predictive and bridging sentences that introduced a temporary transition from the main (predictive) episode. Activation and suppression of inferential and/or textual information were assessed using naming times of word probes that were implied by the preceding text, explicitly mentioned in it, or neither when following control texts. In some cases, a true-false inferential or textual question followed the probe. RESULTS: Naming facilitations were observed for the control but not for the ADHD group, in responding to inference probes that followed the predictive and bridging sentences, and to text probes that followed the predictive sentences. Participants with ADHD were accurate, albeit slower, than controls in answering the true-false questions. CONCLUSIONS: Adolescents with ADHD have difficulties in generating predictive and explanatory inferences and in retaining relevant textual information in working memory while reading, although they can answer questions after reading when texts are relatively short. These findings are discussed with regard to development of comprehension strategies for individuals with ADHD. PMID- 27681539 TI - Definition of Unfit for Standard Acute Myeloid Leukemia Therapy. AB - Determining who is fit or unfit for standard treatments among older adults with acute myeloid leukemia (AML) remains a challenge. However, available evidence can provide guidance on strategies to assess and categorize fitness. Evidence is strongest to guide identification of "frail" older adults at the time of diagnosis based on performance status, physical function, and comorbidity. Many older adults, with adequate performance status and comorbidity burden, however, may be better characterized as "vulnerable". These patients have subclinical impairments that limit resilience when stressed with intensive therapies. More sensitive assessment strategies are needed to differentiate fit and vulnerable older adults regardless of chronologic age. Research is ongoing to identify tools and approaches, such as geriatric assessment, that can enhance characterization of fitness for AML therapies. This review will highlight available evidence for assessment of fitness among older adults with AML and discuss implications for practice and research. PMID- 27681541 TI - Challenges in visceral leishmaniasis control and elimination in the developing countries: A review. AB - Leishmaniasis is a disease caused by an obligate intracellular protozoan that affects animals and human. Transmission is zoonotic and/or anthroponotic through the bite of an infected female sandfly. Control and elimination of visceral leishmaniasis (VL) require proper case detection, identification of reservoir hosts, and launching of effective vector control strategies in endemic areas. The aim of this review was to highlight the challenges in VL control in developing countries. Literatures pertaining to VL burden, diagnosis, prevention and control from the year 1969 to 2014 were systematically reviewed from PubMed, Scopus, Medline and Google scholar sources during July 2015. Poor vector control strategies, limited diagnostic services, drugs, treatments and lack of community awareness are the most important challenges in VL control and elimination especially in endemic areas. Absence of highly sensitive and specific tests, lack of trained man power, and community awareness are the major challenges in VL control. Therefore, proper case diagnosis, community mobilization and launching of effective vector control strategies in endemic areas are vital. PMID- 27681542 TI - Wolbachia: A biological control strategy against arboviral diseases. AB - Vector-borne diseases particularly those transmitted by mosquitoes like Dengue are among the leading causes of mortality and morbidity in human population. There are no effective vaccines or treatment against dengue fever till date and the control methods are limited. So, new approaches are urgently in need to reverse these trends. Vector control is currently the primary intervention tool. Strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. Wolbachia an endosymbiont of arthropod vectors is being explored as a novel ecofriendly control strategy. Studies in Drosophila have shown that Wolbachia can confer resistance to diverse RNA viruses and protect flies from virus-induced mortality. This review was focused on biology of the Wolbachia and its implication as a control measure for arboviral diseases mainly Dengue and Chikungunya. PMID- 27681543 TI - A reassessment of the artificial infection of three predominant mosquito species with Plasmodium vivax in Shandong Province, China. AB - BACKGROUND & OBJECTIVES: Under certain ecological circumstances, pathogens are able to rapidly adapt to new vectors. The great capacity of Plasmodium spp. to adapt to new anopheline mosquito vectors on different continents and the continuous ecological changes attributed to humans might promote their adaptation to culicine vectors, which are known to infect humans. Based on our current knowledge, it is difficult to predict whether such adaptations will occur. This study was aimed to determine the infection susceptibility of Anopheles sinensis, Culex tritaeniorhynchus and Cx. pipiens pallens to Plasmodium vivax in Shandong Province of China. METHODS: The susceptibility of the three predominant species of mosquitoes -An. sinensis, Cx. tritaeniorhynchus and Cx. pipiens pallens in Shandong Province was compared with a direct membrane feeding assay with 15 batches of Shandong strain mono-infected gametocyte-containing blood collected from Plasmodium vivax-infected patients. Infectivity was measured by dissecting the midguts and salivary glands of the mosquitoes. The presence of oocysts and sporozoites was determined by microscopy at 6 and 22 days post-blood feeding. RESULTS: From the 15 batches of mosquitoes that were fed infected blood, oocysts and sporozoites were detected only in 7th, 13th and 15th batches of infection for An. sinensis, and no oocysts or sporozoites were detected in Cx. tritaeniorhynchus or Cx. pipiens pallens. The positive rate of An. sinensis infection was 21.2, 13 and 36.3% in the three batches of mosquitoes, with an average infection rate of 23.5%. INTERPRETATION & CONCLUSION: The susceptibility of An. sinensis to P. vivax was very high in Shandong Province. Cx. tritaeniorhynchus and Cx. pipiens pallens failed to exhibit susceptibility to P. vivax. PMID- 27681544 TI - Impact of insecticide-treated bednet use on malaria prevalence in Benishangul Gumuz regional state, Ethiopia. AB - BACKGROUND & OBJECTIVES: In Ethiopia, nearly 10 million insecticide-treated bednets (ITNs) were distributed between 2004 and 2005; which touched 56 million in 2012. The study was aimed to determine the impact of these bednets on malaria prevalence, in Yaso district of Benishangul-Gumuz region, western Ethiopia. METHODS: A cross-sectional study was conducted during the peak malaria transmission season (October-November, 2014) in the Yaso district, Benishangul Gumuz region. Data on demographic variables, ITN ownership and malaria infection rates were collected using structured questionnaires and blood film tests and analyzed using SAS for windows software. The probability of getting infected (questionnaire and the blood film results) was regressed against groups of explanatory variables, like age, sex, bednet use etc. using multiple logistic regressions. RESULTS: The results revealed that about 40% of the study subjects (384) were positive for Plasmodium falciparum; while P. vivax, P. falciparum and mixed infections accounted for 74.5% of the study subjects. All the 384 study subjects possessed insecticide-treated bednets; 50.5% possessed one, 39.3% two and 10.2% more than two. According to the logistic regression, there was significant association between illness due to malaria and at least one of the explanatory variables (chi26= 271.9, p<0.0001). For all Plasmodium species, education level, and age appeared to be significant beneficial factors (OR<1 and negative beta-values). Occupation was a significant risk factor. Proper ITN utilization improved with increasing educational status. INTERPRETATION & CONCLUSION: Schools may be appropriate for creating awareness and distribution of ITN instead of the current mass campaign, which is less effective. Efforts of stakeholders (schools, community health workers, and the government) should be integrated. PMID- 27681545 TI - A study of spatial and meteorological determinants of dengue outbreak in Bhopal City in 2014. AB - BACKGROUND & OBJECTIVES: Dengue epidemics have been linked to various climatic and environmental factors. Dengue cases are often found in clusters; identification of these clusters in early phase of epidemic can help in efficient control by implementing suitable public health interventions. In year 2014, Bhopal City in Madhya Pradesh, India witnessed an outbreak of dengue with 729 recorded cases. This study reports spatial and meteorological determinants and, demographic and clinical characteristics of the dengue outbreak in Bhopal City. METHODS: A cross-sectional survey of all confirmed cases reported to District Unit of Integrated Disease Surveillance Programme (IDSP), Bhopal was carried out during June to December 2014. Data pertaining to clinical manifestations, health seeking and expenditure were collected by visiting patient's residence. Geographic locations were recorded through GPS enabled mobile phones. Meteorological data was obtained from Indian Meteorological Department website. Multiple linear regression analysis was used to test influence of meteorological variables on number of cases. Clustering was investigated using average nearest neighbour tool and hot-spot analysis or Getis- Ord Gi* statistic was calculated using ArcMap 10. RESULTS: The incidence of confirmed dengue as per IDSP reporting was 38/100,000 population (95% CI, 35.2- 40.7), with at least one case reported from 73 (86%) of the total 85 wards. Diurnal temperature variation, relative humidity and rainfall were found to be statistically significant predictors of number of dengue cases on multiple linear regressions. Statistically significant hot-spots and cold-spots among wards were identified according to dengue case density. INTERPRETATION & CONCLUSION: Seasonal meteorological changes and sustained vector breeding contributed to the dengue epidemic in the post-monsoon period. Cases were found in geographic clusters, and therefore, findings of this study reiterate the importance of spatial analysis for understanding the pace of outbreak and identification of hot-spots. PMID- 27681546 TI - Clinico-laboratory profile of dengue patients returning from tropical areas to Poland during 2010-15. AB - BACKGROUND & OBJECTIVES: Dengue is a mosquito-borne viral disease, incidences of which have increased rapidly in the past decade. About 400 million new infections are recorded annually worldwide, and 40% of the human population lives in the areas at risk of dengue transmission. In this study, the clinical and laboratory profile of dengue diagnosed patients returning to Poland from tropical areas has been analyzed. METHODS: This is a retrospective study of 65 patients based on clinical symptoms and serological tests conducted in the Department of Tropical Parasitology of Institute of Maritime and Tropical Medicine (IMTM) in Gdynia, Poland during 2010-15. The diagnosis of dengue virus (DENV) infection was based on the detection of specific immunoglobulin M (IgM) and IgA antibodies performed by specific ELISA assays. The samples were considered as positive, if the absorbance was >10% above the cut-off value. RESULTS: Among 65 persons with dengue selected for the analysis, 59 patients were admitted to the hospital because of clinical symptoms of the disease; the six persons initially asymptomatic were hospitalized due to routine control treatment returning from tropical regions. Patients reported various destinations, purpose and duration of their travels. All of them had returned from dengue endemic regions and were positive for IgM antibodies against DENV. Common clinical symptoms observed were fever (ranging from 38 to 40 degrees C in 43% of patients), weakness, headache and rash. Laboratory tests revealed elevated levels of transaminase activity, leukopenia and thrombocytopenia in 35.3, 24.6 and 20% of patients, respectively. INTERPRETATION & CONCLUSION: The number of Polish travelers to subtropics and tropics increases every year. As cases of fever and other symptoms appear to be increasingly in Polish people returning from tropical regions of Asia, America and Africa, their screening and management should be taken seriously. The study also suggests that the disease might be more widespread than it was known previously. PMID- 27681547 TI - Genetic characterization and molecular phylogeny of Aedes albopictus (Skuse) species from Sonitpur district of Assam, India based on COI and ITS1 genes. AB - BACKGROUND & OBJECTIVES: Aedes albopictus (Skuse) is one of the major vectors of dengue which is an emerging threat in Northeast part of India. The morphological characterisation of mosquitoes is time consuming and lacks accuracy for distinguishing closely related species. Hence, molecular methods of mosquito identification, genetic diversity and molecular phylogeny have gained increased importance. This study was aimed to identify and characterize the most abundant species of Aedes vectors collected from different breeding spots in Assam, Northeast India employing molecular as well as bioinformatics tools. METHODS: Ae. albopictus species was genetically characterized with internal transcribed spacer1 (ITS1) and cytochrome c oxidase subunit I (COI) genes and sequence analysis was carried out following molecular methods like PCR amplification, DNA sequencing and multiple sequence analysis. Maximum likelihood molecular phylogeny was reconstructed to define the evolutionary relationship among studied isolates and isolates from other parts of Southeast Asia. RESULTS: Molecular study revealed that all five subject specimens belonged to Ae. albopictus species as per both ITS1 and COI genes. Maximum likelihood tree based on ITS1 and COI genes showed that isolates were distinctly grouped into separate clusters. Almost similar pattern of amino acid frequencies in COI gene was found amongst the five studied isolates. However, amino acid frequency in ITS1 gene was found to be dissimilar, indicating polymorphisms in this gene, among the isolates. INTERPRETATION & CONCLUSION: This is the first report among the Northeastern states of India describing the genetic make-up of Ae. albopictus species by virtue of highly conserved mitochondrial (mt) DNA and ribosomal (r) DNA gene sequences. This study also illustrates that the sequence diversity of these two genes in this mosquito species differs geographically which differentiate a population and brings unique identity. PMID- 27681548 TI - Ecoepidemiological characteristics of a hypoendemic focus of zoonotic cutaneous leishmaniasis in north Iran (southeast of Caspian Sea). AB - BACKGROUND & OBJECTIVES: Leishmaniasis is an endemic parasitic disease reported sporadically throughout Iran. Golestan province is one of the 17 zoonotic cutaneous leishmaniasis (ZCL) foci. In this study, ecoepidemiological characteristics of ZCL were investigated in Gonbad-e Kavus County, Golestan province of Iran. METHODS: This cross-sectional study was carried out in three endemic villages and one ZCL-free village by exploiting a stratified random sampling methodology in 2013. To understand particular time-allocation and activity patterns, sandflies were entrapped twice per month using sticky traps from May to October 2013. Records of daily maximum and minimum temperatures ( degrees C) obtained from the meteorological station were used to calculate accumulated degree days (ADD) for Phlebotomus papatasi sandflies using an online software, viz. degree-day calculator, available from the website of Integrated Pest Management, University of California. The computational ADD and expected stage appearance for P. papatasi sandflies were evaluated along with the phenological events. Human infection indices were investigated in the study areas as well. RESULTS: In the entomological survey, a total of 13 different sandfly species were identified. Sergentomyia sintoni (66.8%) and P. papatasi (20%) were observed to be the most dominant species. Monthly activity of the different species of sandflies started from early May to mid-October, with two peaks observed in early July and mid- September, and the peak of hourly activity occurred at night (1900-2000 hrs). According to the phenological study, population dynamics of P. papatasi was completely in agreement with ADD required for the various stages of their growth. Epidemiologically, the highest incidence of ZCL was observed in the age group of 30-34 yr (29.4%). INTERPRETATION & CONCLUSION: Higher incidence of the disease was seen in the northern and the northeastern parts of the province bordered by Turkmenistan. The most effective alternative for controlling the disease in this hypoendemic focus is health education regarding personal protection from infected P. papatasi. The long-term studies are imperative for better understanding and estimation of the factors affecting ZCL transmission in the endemic areas. PMID- 27681549 TI - NRAMP1 gene polymorphisms and cutaneous leishmaniasis: An evaluation on host susceptibility and treatment outcome. AB - BACKGROUND & OBJECTIVES: Association between polymorphisms in the natural resistance associated macrophage protein 1 (NRAMP1) gene and susceptibility to cutaneous leishmaniasis (CL) has been demonstrated worldwide; however, the reported results were inconsistent. This study aimed to determine the association of NRAMP1 variants with susceptibility to CL infection and patients' response to treatment in Isfahan province of Iran. METHODS: Peripheral blood samples were collected from 150 patients with CL and 136 healthy controls. The CL patients were treated with intralesional injection of meglumine antimoniate. The polymorphic variants at NRAMP1 (A318V and D543N) were analyzed using PCR-RFLP. The chi-square test and Fisher's exact test were used to compare frequencies of alleles and genotypes of polymorphisms between patient and healthy control populations. RESULTS: There was a statistically significant difference in the D543N (rs17235409) polymorphism between the CL patients and healthy controls (p=0.008). However, no significant association was detected for A318V (rs201565523) polymorphism between groups (p=0.26). In addition, there was a lack of association between D543N and A318V genotypes with response to treatment (p=0.54 and p=0.31, respectively). INTERPRETATION & CONCLUSION: The results indicated that genetic variations of D543N (rs17235409) might be associated with susceptibility to CL infection. These data may be used for detection of sensitive individuals and prevention of CL in endemic areas. PMID- 27681550 TI - Role of An. culicifacies as a vector of malaria in changing ecological scenario of Northeastern states of India. AB - BACKGROUND & OBJECTIVES: Malaria has become endemic and subject of concern in most part of the India especially Northeastern states of India. Surveys before 2000 revealed that Anopheles minimus was major vector responsible for transmission of malaria in this region followed by An. dirus and An. fluviatilis. However, recent studies indicate replacement of An. minimus vector by An. culicifacies due to different ecological changes and change in landuse pattern etc. The objective of present study was to explore the vectorial role of An. culicifacies in transmission of malaria in four malaria endemic states, viz. Assam, Meghalaya, Manipur and Sikkim of India. METHODS: The seven surveys were conducted in 176 selected villages belonging to eight districts of the four states in both pre-monsoon (March-April) and post-monsoon (September-October) seasons from 2010 to 2013. However, in 2011 surveys could not be carried out due to public inconvenience in pre-monsoon season. For vectorial role of all vector species collected, ELISA and PCR were assayed. RESULTS: A total of 19,173 specimens belonging to 30 anopheline species were collected, out of which 4315 belonged to four established vector species. In total, 4183 specimens were processed through ELISA, out of which 236 specimens were found positive for circumsporozoite (CS) protein. Further, infectivity was confirmed by PCR in 35 samples, of which 12 samples were found positive for Plasmodium falciparum and three for P. vivax. Out of 12 Plasmodium falciparum positive samples, nine samples were positive for An. culicifacies, two for An. fluviatilis and one for An. minimus. While out of three Plasmodium vivax positive samples, two samples were positive for An. dirus and one sample was positive for An. culicifacies. INTERPRETATION & CONCLUSION: Anopheles culicifacies replaced the An. minimus, the vector of malaria in Northeastern states of India, as it was found to be highly infected with malaria parasite as compared to An. minimus by ELISA and PCR analysis, and thus playing a major role in malaria transmission in this region. The ecological changes like deforestation, development of irrigation channels and change in landuse pattern, have helped in evolution of An. culicifacies in the study area. Therefore, modified vector control strategies are required on urgent basis. PMID- 27681552 TI - Knowledge, attitude, behaviour and practices (KABP) of the community and resultant IEC leading to behaviour change about dengue in Jodhpur City, Rajasthan. AB - BACKGROUND & OBJECTIVES: In recent years dengue has been witnessed as an emerging public health problem. Therefore, the present study was undertaken in order to assess the knowledge, attitude, behaviour and practices (KABP) adopted by the society for its control and prevention. The changes in behaviour of community after imparting health education were also recorded to determine the effectiveness of information, education and communication (IEC) for dengue prevention and control in Jodhpur City of Rajasthan, India. METHODS: A threefold study was conducted in Jodhpur City regarding KABP about dengue fever amongst the community. Out of 106 cases of dengue reported from Jodhpur City in the year 2008, only 20 households (HHs) could be located. Therefore, nine HHs around one dengue positive household were selected so as to cover the sample size of 200 HHs for eliciting information through structured recorded interview-schedule. Health education as provided through audiovisuals and group discussion etc. and resultant change in KABP was recorded again through interview of respondents from 100 households. RESULTS: Prevention from dengue mosquito bites through mats and liquid vaporizer was known to 32 and 22% HHs respectively. Inhabitants of 87% HHs preferred to visit private health facility, 85% of HHs were not aware about the symptoms of dengue, while74% HHs stated that dengue mosquito breeds in dirty water. Awareness about source of mosquito breeding and source reduction was found to be very poor, i.e. 3 and 13% which improved to 78 and 88% respectively after undertaking IEC activities. INTERPRETATION & CONCLUSION: Being urban area, the economic condition and education level were somewhat similar and satisfactory in Jodhpur City. IEC resulted in significant improvement in knowledge about transmission, breeding habitats of mosquito transmitting dengue, source reduction and health treatment seeking behaviour at government facility. Through such mass awareness programmes in the communities, desired results in prevention and control of dengue transmission can be achieved. PMID- 27681551 TI - Influence of socioeconomic aspects on lymphatic filariasis: A case-control study in Andhra Pradesh, India. AB - BACKGROUND & OBJECTIVES: Lymphatic filariasis (LF) is a major public health problem in India. The objective of the study was to assess the impact of socioeconomic conditions on LF in Chittoor district of Andhra Pradesh, India. METHODS: A survey was carried out from 2004 to 2007 during which, an epidemiological and socioeconomic data were collected and analysed. The microfilaria (mf) positive samples were taken as cases and matched with control group by sex and age (1:1) for case-control study. Bivariate and multivariate logistic regression was used to identify the potential risk factors for filariasis. Using principal component analysis (PCA), a socioeconomic index was developed and the data/scores were classified into low, medium and high categories. RESULTS: In total 5,133 blood smears were collected, of which 77 samples were found positive for microfilaria (1.52%). Multivariate analysis showed that the risk of filariasis was higher in groups of people with income < ?1000 per month [OR = 2.752 (95%CI, 0.435-17.429)]; ? 1000-3000 per month [3.079 (0.923-0.275)]; people living in tiled house structure [1.641 (0.534-5.048)], with kutcha (uncemented) drainage system [19.427 (2.985- 126.410)], respondents who did not implemented mosquito avoidance measures [1.737 (0.563-5.358)]; and in people who were not aware about prevention and control of filariasis [1.042 (0.368-2.956)]. PCA showed that respondents with low (41.6%) and medium (33.8%) socioeconomic status are more prone to filariasis (p=0.036). INTERPRETATION & CONCLUSION: The cross sectional study showed that the population with low and medium socioeconomic status are at higher risk of filariasis. The identified socioeconomic risk factors can be used as a guideline for improving the conditions for effective management of filariasis. PMID- 27681554 TI - Neuro-invasion by a zoonotic arbovirus. PMID- 27681553 TI - Evaluation of ImmuneMed scrub typhus rapid test kit, for diagnosis of scrub typhus. PMID- 27681555 TI - Hyperparasitaemia and phagocytosis of Plasmodium falciparum in fatal cerebral malaria. PMID- 27681556 TI - Fluctuations in daily energy intake do not cause physiological stress in a Neotropical primate living in a seasonal forest. AB - Animals may face periods of nutritional stress due to short-term food shortage and/or low energy consumption associated with seasonal fluctuations in resource availability. We tested the hypothesis that periods of restricted macronutrient and energy intake result in energy deficits and physiological stress in wild black howler monkeys (Alouatta pigra) inhabiting seasonal tropical semi-deciduous forests. We conducted full-day follows of focal animals recording feeding rates, time spent feeding, and total amount of food ingested. We carried out nutritional analysis of foods collected from feeding trees and calculated the daily nutrient and energy intake of each focal individual. Fecal glucocorticoid metabolites (fGCM) of focal animals were used as an indicator of physiological stress. We found that fluctuations in daily energy intake across seasons did not have significant effects on fGCM of individuals. However, protein intake was negatively associated with fGCM, highlighting the interplay among macronutrients, metabolism, and the endocrine system. Fecal glucocorticoid metabolites were also positively related to fruit availability, but this relationship was most likely due to social stress associated with intergroup encounters and resource defense that occurred when preferred trees were fruiting. Behavioral strategies such as dietary shifts and nutrient mixing, and metabolic adaptations such as low energy expenditure allowed individuals to fulfill their minimum energy requirements even during periods of decreased resource availability and intake. The present study suggests that seasonal variations in food, macronutrient, and energy acquisition may have limited physiological costs for animals that exploit different types of plant resources such as howler monkeys. PMID- 27681557 TI - Assessment of the Psychosocial Adjustment of Well Elderly Residing in Retirement Communities. AB - Moving to a retirement community involves a major life transition that requires adjustment to a new way of life. The purpose of this study was to develop a tool to assess the psychosocial adjustment of residents. Using the Life Patterns Model as a conceptual framework, residents of 3 retirement communities (n = 240 residents) were surveyed. Median ages were ~84 years, Nearly 85% (202) reported that they feel good about themselves and most (92.5%; n = 221) have things to do that they enjoy. Health status was strongly associated with having nearby relatives (rs = -.232, p > .000, n = 239). A factor analysis supported the use of the conceptual framework. Findings indicate that the tool can used for the designed purpose. PMID- 27681558 TI - Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase. AB - Activation of the thick ascending limb (TAL) Na+-K+-2Cl- cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET levels (-56 +/- 3% for 5,6-EET, -50 +/- 3.4% for 11,12-EET, and -60 +/- 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 +/- 37%) and protein levels (+120 +/- 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 MUM 14,15-EET for 30 min reduced phosphorylation of NKCC2 at the AVP-sensitive threonine residues T96 and T101 ( 66 +/- 5%; P < 0.05), while 14,15-DHET had no effect. Concomitantly, isolated perfused cortical thick ascending limb pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symmetric chloride concentrations. In summary, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis. PMID- 27681559 TI - Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species. AB - There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with either l-NAME or l-NAME together with the superoxide scavenger Tempol, or together with l-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, theta) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 A). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of theta for Ficoll repeatedly during up to 2 h. l-NAME increased theta for Ficoll70A from 2.27 +/- 1.30 * 10-5 to 8.46 +/- 2.06 * 10-5 (n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed with l-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo by l-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo. PMID- 27681560 TI - Characterization and phosphoproteomic analysis of a human immortalized podocyte model of Fabry disease generated using CRISPR/Cas9 technology. AB - Fabry nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the main substrate of alpha-galactosidase A (alpha-Gal A), progressively accumulates within cells in a variety of tissues. Establishment of cell models has been useful as a tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Our podocytes lack detectable alpha-Gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of alpha-gal A deficiency, we used a high throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9 edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD. PMID- 27681562 TI - The nephron (pro)renin receptor: function and significance. AB - The (pro)renin receptor (PRR) is a multifunctional protein that is part of the renin-angiotensin system and is an important accessory molecule for the vacuolar H+-ATPase. The PRR is widely expressed in the kidney with relatively high abundance in the distal nephron. Determining the physiological relevance of the PRR has been challenging due to early lethality in whole animal and cell-specific PRR knockout models. Recently, viable renal cell-specific PRR knockout mice have been developed; these studies suggest that PRR in the nephron can modulate renal function via angiotensin II (ANG II)-dependent and -independent cell signaling pathways. In this mini-review, we highlight new developments in nephron PRR function in health and in pathophysiological conditions. PMID- 27681561 TI - Deletion of proton-sensing receptor GPR4 associates with lower blood pressure and lower binding of angiotensin II receptor in SFO. AB - Diets rich in grains and meat and low in fruits and vegetables (acid-producing diets) associate with incident hypertension, whereas vegetarian diets associate with lower blood pressure (BP). However, the pathways that sense and mediate the effects of acid-producing diets on BP are unknown. Here, we examined the impact of the deletion of an acid sensor GPR4 on BP. GPR4 is a proton-sensing G protein coupled receptor and an acid sensor in brain, kidney, and blood vessels. We found that GPR4 mRNA was higher in subfornical organ (SFO) than other brain regions. GPR4 protein was abundant in SFO and present in capillaries throughout the brain. Since SFO partakes in BP regulation through the renin-angiotensin system (RAS), we measured BP in GPR4-/- and GPR4+/+ mice and found that GPR4 deletion associated with lower systolic BP: 87 +/- 1 mmHg in GPR4-/- (n = 35) vs. 99 +/- 2 mmHg (n = 29) in GPR4+/+; P < 0.0001, irrespective of age and sex. Angiotensin II receptors detected by 125I-Sarthran binding were lower in GPR4-/- than GPR4+/+ mice in SFO and in paraventricular nucleus of hypothalamus. Circulating angiotensin peptides were comparable in GPR4-/- and GPR4+/+ mice, as were water intake and excretion, serum and urine osmolality, and fractional excretion of sodium, potassium, or chloride. A mild metabolic acidosis present in GPR4-/- mice did not associate with elevated BP, implying that deficiency of GPR4 may preclude the effect of chronic acidosis on BP. Collectively, these results posit the acid sensor GPR4 as a novel component of central BP control through interactions with the RAS. PMID- 27681564 TI - The Refugee Health Nurse Liaison: a nurse led initiative to improve healthcare for asylum seekers and refugees. AB - Asylum seekers and refugees experience a range of barriers to health service access and competent use. The Refugee Health Nurse Liaison initiative was piloted at a hospital in a high-settlement region of Victoria, Australia. This initiative aimed to build capacity within the health sector to more effectively respond to the needs of asylum seekers and refugees. A mixed-methods evaluation was undertaken to: describe issues encountered by asylum seekers and refugees within the hospital setting; capture the nature of the Refugee Health Nurse Liaison position; and document key outputs. Throughout the pilot period, 946 patients were referred to the role, of which 99% received an assessment of physical, mental, and social health. Refugee Health Nurse Liaisons effectively provided clinical support, advocacy, education, referrals, and both formal and informal capacity building. Learnings from this model are transferable to services in high settlement regions, and could have application in improving patient care more broadly. PMID- 27681563 TI - Structural determinants of NH3 and NH4+ transport by mouse Rhbg, a renal Rh glycoprotein. AB - Renal Rhbg is localized to the basolateral membrane of intercalated cells and is involved in NH3/NH4+ transport. The structure of Rhbg is not yet resolved; however, a high-resolution crystal structure of AmtB, a bacterial homolog of Rh, has been determined. We aligned the sequence of Rhbg to that of AmtB and identified important sites of Rhbg that may affect transport. Our analysis positioned three conserved amino acids, histidine 183 (H183), histidine 342 (H342), and tryptophan 230 (W230), within the hydrophobic pore where they presumably serve to control NH3 transport. A fourth residue, phenylalanine 128 (F128) was positioned at the upper vestibule, presumably contributing to recruitment of NH4+ We generated three mutations each of H183, H342, W230, and F128 and expressed them in frog oocytes. Immunolabeling showed that W230 and F128 mutants were localized to the cell membrane, whereas H183 and H342 staining was diffuse and mostly intracellular. To determine function, we compared measurements of NH3/NH4+ and methyl amine (MA)/methyl ammonium (MA+)-induced currents, intracellular pH, and surface pH (pHs) among oocytes expressing the mutants, Rhbg, or injected with H2O. In H183 and W230 mutants, NH4+-induced current and intracellular acidification were inhibited compared with that of Rhbg, and MA induced intracellular alkalinization was completely absent. Expression of H183A or W230A mutants inhibited NH3/NH4+- and MA/MA+-induced decrease in pHs to the level observed in H2O-injected oocytes. Mutations of F128 did not significantly affect transport of NH3 or NH4+ These data demonstrated that mutating H183 or W230 caused loss of function but not F128. H183 and H342 may affect membrane expression of the transporter. PMID- 27681565 TI - Non-intestinal type sinonasal cancers and exposure to occupational carcinogens: a case-control study. AB - BACKGROUND: Sinonasal cancers are rare, often fatal, tumors with a very high proportion of cases attributable to occupational exposures. The relevance of different carcinogens deeply varies among histological subtypes, with intestinal type adenocarcinomas (ITAC) characterized by a very large proportion of workers exposed to wood dust. The role of occupation in the etiology of other histotypes is less clear and more disputed, with authors questioning the possible occupational origin of non-ITAC cancers. METHODS: We conducted a hospital-based case-control study on 50 consecutives non-ITAC cancers and 50 controls, in Varese, Italy. Relative risks for previous exposure to carcinogens (any or single agent, i.e. wood/leather dust, solvents, metals) were calculated by multivariate logistic regression models adjusted for age, gender, smoking habits and residence (within or outside the Lombardy region). RESULTS: Having been exposed to any occupational carcinogen carried an OR of 3.04 (95%CI: 0.91-10.21). Considering single carcinogens, we observed no increased risk for wood dust exposure (OR=1.02, 95%CI: 0.21-4.94), while a large effect associated with previous exposure to other recognized carcinogens (leather dust, solvents or metals) appeared: OR=7.01 (95%CI: 1.51-32.8). DISCUSSION: Our results highlighted the importance of properly considering sinonasal cancers histological subtypes when investigating the role of occupational carcinogens. Grouping together all sinonasal cancers may end up in underestimating the role of wood in ITAC etiology as well as the relevance of other occupational exposures for non-ITAC tumors. All sinonasal cancers deserve a thorough investigation of the occupational history. PMID- 27681566 TI - Geographical patterns of mesothelioma incidence and asbestos exposure in Lombardy, Italy. AB - BACKGROUND: Measuring malignant mesothelioma (MM) occurrence is a useful means to monitor the impact of past asbestos exposure and possibly identify new sources of asbestos exposure. OBJECTIVES: Aim of this study is to describe the results of the MM registry of the Lombardy Region, North-West Italy, the most populated (currently, 10 million inhabitants) and industrialised Italian region. METHODS: We extracted from the Lombardy Region Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) database all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in 2000 through 2012. For each Province, we calculated crude and standardised incidence rates using Italy 2001, European, and world (Segi's) standard populations. To examine spatial patterns of MM occurrence across municipalities we drew maps of crude rates smoothed according to the Besag, York and Mollie (BYM) method. RESULTS: We recorded 4442 MM cases (2850 in men and 1592 in women), representing about one fourth of MM cases occurring in Italy. Occupational exposure was more frequent in men (73.6%) than in women (38.2%). The crude regional rates were 4.7 per 100,000 person-years in men and 2.5 per 100,000 person-years in women. The highest rates were observed in the Pavia Province (crude rates: 8.7 per 100,000 in men and 5.3 and per 100,000 person-years in women). CONCLUSIONS: This study documented high MM occurrence in both genders, attributable to extensive asbestos exposure in the past. PMID- 27681567 TI - Spinal load in nurses during emergency lifting of obese patients: preliminary results. AB - BACKGROUND: Nurses are exposed to the risk of injury while handling patients. This is particularly true for obese patients. OBJECTIVE: The goal of this paper is to estimate the spinal loads and the related risk of injury to nurses while lifting obese patients from the floor with a bariatric sheet during a hospital emergency. METHODS: Six male nurses participated in this study. The biomechanical analysis focused on the lifting strategy. Thirty obese in-patients were enrolled to take part in the experimental study and divided into three groups according to their Body Mass Index (BMI). Three-dimensional motion analysis was conducted using an optoelectronic system. The trunk kinematics and the loading on the spines of the operating nurses were computed. RESULTS: Our data showed that when the nurse was operating from the central handle, his trunk was more flexed at the end of the lift with a reduced range of motion. The values were higher when the nurse lifted patients with higher BMIs. All kinetic parameters and tension in the lumbar muscles at the end of the movement were characterised by lower values for the nurse placed beside the patient's head or feet if compared to the operator positioned beside the central handle in all patient groups. CONCLUSIONS: Our preliminary data suggest that only the reaction load on the spine of the nurse holding the central handle, closest to the patient's centre of mass, seems to exceed the recommended safety limits. PMID- 27681568 TI - From work-related stress evaluation to organizational wellbeing promotion: the case of an Italian pharmaceutical company. AB - BACKGROUND: Work-related stress evaluation is a legal requirement for companies that, in some cases, might be seen as an opportunity to examine wellbeing at work and the dimensions related to it, through the involvement of employees. To that end, this study considers the job demands-resources model as a theoretical framework. OBJECTIVES: The study has a twofold objective: a) to describe the process of subjective evaluation carried out in the Italian plant of a pharmaceutical company; and b) to show and discuss results of the analyses performed on variables, examining in detail the relationship between two outcomes (job satisfaction and emotional exhaustion) and some job demands (workload and job effort), job resources (safety climate, clarity of roles, clarity and applicability of procedures, supervisor relational justice and colleague support), and personal resources (internal locus of control and job-related self efficacy). METHODS: The research was conducted through focus groups and a self report questionnaire that involved all plant employees. Final respondents were 143 (85.1% of employees). RESULTS: The regression model, with job satisfaction as a dependent variable, showed a positive relationship with some organizational resources: clarity of roles, clarity and applicability of procedures, supervisor relational justice and colleague support. The regression model, with emotional exhaustion as a dependent variable, showed a positive relationship with two job demands, workload and job effort, and a negative relationship with job-related self-efficacy. CONCLUSIONS: The study confirmed how important it is to consider wellbeing at work, in its cognitive and emotional dimensions, and its relationship with job demands and resources, within subjective evaluation of work related stress. Starting from the study results, the research identified a plan of interventions designed for specific areas of improvement. PMID- 27681570 TI - National survey on workplace safety and prevention services: regional differences. AB - BACKGROUND: Occupational Safety and Health (OSH) Services, with inspections and support activities to workers and to enterprises, have a relevant role in the field of safety and health in the workplace. OBJECTIVES: The aim of this study, part of the INSuLa Project, is to realize a national survey about risk perception of OSH and awareness about OSH issues in the context of the Italian OSH legislative framework (Legislative Decree 81/08 and subsequent modifications and integrations) implementation, with involvement of the OSH Services operators. METHODS: The Survey involved a representative national sample of the OSH Services operators. After an analysis of background literature and a comparison with Operating Units involved in the Project, an ad hoc questionnaire was developed and administered to the sample to evaluate the topics of the Survey. RESULTS: The study has been conducted on a sample of 678 OSH Services operators. The Survey showed in Italy an important organizational and procedural inhomogeneity perceived by OSH Services operators. CONCLUSIONS: This study highlighted the relevance perceived by OSH Services operators to develop a system of safety culture dissemination to reduce accidents at work and improve the management of occupational risks (traditional and emerging). PMID- 27681569 TI - Psychosocial risks assessment at hospital: development of a French questionnaire. AB - BACKGROUND: In order to improve the well-being, health, and performance of hospital workers, it should be important to focus on the psychosocial risk (PSR) factors in the work environment and on job satisfaction. Although many epidemiological questionnaires are used to measure PSR among healthcare workers, no specific existing model can be applied to all categories of hospital workers. OBJECTIVE: To develop a short French self-administered instrument for measuring the PSR for hospital workers: the PSRH questionnaire. METHODS: The content of the PSRH questionnaire was partly derived from the well-known and standardized questionnaires (Karasek Job Content and Siegriest effort-reward imbalance questionnaires). The validation process was carried out in all the departments of a large public university hospital (Marseille, France). Eligible workers were adult employees present on the day of the assessment: healthcare, administrative, and technical workers. A total of 2203 subjects were included from September 2012 to October 2013. RESULTS: The PSRH contains 24 items describing 6 dimensions (Management, cooperation and hierarchical support; Requirements, constraints and autonomy related to work; Support and relationship with the team; Complexity of the work and unforeseen factors; Meaning of work and recognition; and Conciliation work - work out). The six-factor structure presented satisfactory internal consistency and scalability. All the scores showed significant correlations with a well-being score. Acceptability was high. CONCLUSION: The PSRH is a self-administered instrument assessing PSR at hospital that presents satisfactory psychometric properties. Future studies should identify factors that determine low- and high-risk workers in order to implement appropriate preventing strategies. PMID- 27681571 TI - From the addiction rehabilitation program to the return to work: results of an employment and social intervention among young adults with substance dependence. AB - INTRODUCTION: Substance dependence problems are considered to be a relevant issue for a large proportion of the working population and represent a huge health and occupational cost. However, few studies have examined the return to work after addiction problems. AIMS: This exploratory follow-up study aims to evaluate the return to work, in terms of employment outcomes, perceived work environment and physical and mental health of patients who have completed an addiction rehabilitation program and an employment and social intervention. METHODS: The sample includes 51 participants with a baseline diagnosis of substance abuse disorder who have completed a rehabilitation and a social-occupational intervention. Patients were assessed by means of self-report questionnaires referring to perceptions of the work environment, individual characteristics and mental and physical health. RESULTS: The results show that the majority of the sample (88.2%) is employed at follow-up and refers positive perceptions about the psychosocial work environment, the mental and physical health and the stabilization of the change. The factors that significantly influence job satisfaction are work ability (p=0.02), work engagement (p=0.04) and absence of desire (p=0.05). CONCLUSIONS: The present study shows that many patients some years after the rehabilitation program have kept their job with positive levels of individual and organizational well-being. Work is not perceived as a source of stress but it represents a protective factor for health, personal identity and social integration. PMID- 27681572 TI - STEPWISE - STructured lifestyle Education for People WIth SchizophrEnia: a study protocol for a randomised controlled trial. AB - BACKGROUND: People with schizophrenia are two to three times more likely to be overweight than the general population. The UK National Institute of Health and Care Excellence (NICE) recommends an annual physical health review with signposting to, or provision of, a lifestyle programme to address weight concerns and obesity. The purpose of this randomised controlled trial is to assess whether a group-based structured education programme can help people with schizophrenia to lose weight. METHODS: Design: a randomised controlled trial of a group-based structured education programme. SETTING: 10 UK community mental health trusts. PARTICIPANTS: 396 adults with schizophrenia, schizoaffective, or first-episode psychosis who are prescribed antipsychotic medication will be recruited. Participants will be overweight, obese or be concerned about their weight. INTERVENTION: participants will be randomised to either the intervention or treatment as usual (TAU). The intervention arm will receive TAU plus four 2.5-h weekly sessions of theory-based lifestyle structured group education, with maintenance contact every 2 weeks and 'booster' sessions every 3 months. All participants will receive standardised written information about healthy eating, physical activity, alcohol and smoking. OUTCOMES: the primary outcome is weight (kg) change at 1 year post randomisation. Secondary outcomes, which will be assessed at 3 and 12 months, include: the proportion of participants who maintained or reduced their weight; waist circumference; body mass index; objectively measured physical activity (wrist accelerometer); self-reported diet; blood pressure; fasting plasma glucose, lipid profile and HbA1c (baseline and 1 year only); health-related quality of life (EQ-5D-5L and RAND SF-36); (adapted) brief illness perception questionnaire; the Brief Psychiatric Rating Scale; the Client Service Receipt Inventory; medication use; smoking status; adverse events; depression symptoms (Patient Health Questionnaire-9); use of weight-loss programmes; and session feedback (intervention only). Outcome assessors will be blind to trial group allocation. Qualitative interviews with a subsample of facilitators and invention-arm participants will provide data on intervention feasibility and acceptability. Assessment of intervention fidelity will also be performed. DISCUSSION: The STEPWISE trial will provide evidence for the clinical and cost-effectiveness of a tailored intervention, which, if successful, could be implemented rapidly in the NHS. TRIAL REGISTRATION: ISRCTN19447796 , registered on 20 March 2014. PMID- 27681573 TI - Candida glabrata species complex prevalence and antifungal susceptibility testing in a culture collection: First description of Candida nivariensis in Argentina. AB - The presence of the cryptic species belonging to the Candida glabrata complex has not been studied in Argentina. We analyzed a collection of 117 clinical isolates of C. glabrata complex belonging to a National Culture Collection of Instituto Nacional de Microbiologia "Dr. Carlos G. Malbran" from Argentina (40 isolates from blood samples, 18 from other normally sterile sites, 20 from vagina, 14 from urine, 7 from oral cavity, 3 from catheter, 1 from a stool sample and 14 isolates whose clinical origin was not recorded). The aims of this work were to determine the prevalence of the cryptic species Candida nivariensis and Candida bracarensis and to evaluate the susceptibility profile of isolates against nine antifungal drugs. Identification was carried out by using classical phenotypic tests, CHROMagarTM Candida, PCR and MALDI-TOF. The minimal inhibitory concentrations of amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, voriconazole, ketoconazole, posaconazole, caspofungin and anidulafungin were determined according to the EDef 7.3 (EUCAST) reference document. Of the 117 isolates, 114 were identified as C. glabrata and three as C. nivariensis by using PCR and MALDI TOF. There were no major differences between C. nivariensis and C. glabrata susceptibility profiles. No resistant strains were found to echinocandins. We have found that the percentage of C. nivariensis in our culture collection was 2.56. This is the first description of C. nivariensis in Argentina, and data obtained could contribute to the knowledge of the epidemiology of this cryptic species. PMID- 27681574 TI - Dyslipidaemia: Balancing the benefits and risks of statin therapy. PMID- 27681576 TI - Enhancing the value of clinical trials: the role of data sharing. PMID- 27681575 TI - Bioresorbable vascular scaffolds - basic concepts and clinical outcome. AB - The introduction of percutaneous treatment of coronary artery stenosis with balloon angioplasty was the first revolution in interventional cardiology; the advent of metallic coronary stents (bare and drug-eluting) marked the second and third revolutions. However, the latest generation of drug-eluting stents is limited by several factors. Permanent vessel caging impairs arterial physiology, and the incidence of very late stent thrombosis - although lower with the second generation than with the first generation of drug-eluting stents - remains a major concern. This complication is mainly related to the presence of permanent metallic implants, chronic degeneration triggered by an inflammatory response to the coating polymer, and/or adverse effects of antiproliferative drugs on endothelial regeneration. In 2011, self-degrading coronary stents - the bioresorbable vascular scaffolds (BVS) - were introduced into clinical practice, showing good short-term results owing to their adequate strength. The advantage of these devices is the transient nature of vascular scaffolding, which avoids permanent vessel caging. In this Review, we summarize the latest research on BVS, with a particular emphasis on the implantation technique (which is different from that used with metallic stents) to outline the concept that BVS deployment methods have a major effect on procedural success and prognosis of patients with coronary artery stenosis. Furthermore, the clinical outcome of BVS in randomized clinical trials and in phase IV studies are discussed in different pathophysiological settings, such as stable or acute coronary disease. Finally, all the available data on the safety profile of BVS regarding scaffold thrombosis are discussed. PMID- 27681581 TI - Corrigendum. PMID- 27681579 TI - Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors. AB - PURPOSE: A capsule formulation of the tyrosine kinase inhibitor dovitinib (TKI258) was recently studied in a phase 3 renal cell carcinoma trial; however, tablets are the planned commercial formulation. Therefore, this randomized 2-way crossover study evaluated the bioequivalence of dovitinib tablet and capsule formulations in pretreated patients with advanced solid tumors, excluding breast cancer. METHODS: In this 2-part study, eligible patients received dovitinib 500 mg once daily on a 5-days-on/2-days-off schedule. During the 2-period bioequivalence phase, patients received their initial formulation (capsule or tablet) for 3 weeks before being switched to the alternative formulation in the second period. Patients could continue to receive dovitinib capsules on the same dosing schedule during the post-bioequivalence phase. RESULTS: A total of 173 patients were enrolled into the bioequivalence phase of the study (capsule -> tablet, n = 88; tablet -> capsule, n = 85), and 69 patients had evaluable pharmacokinetics (PK) for both periods. PK analyses showed similar exposure and PK profiles for the dovitinib capsule and tablet formulations and supported bioequivalence [geometric mean ratios: AUClast, 0.95 (90 % CI 0.88-1.01); C max, 0.98 (90 % CI 0.91-1.05)]. The most common adverse events, suspected to be study drug related, included diarrhea (60 %), nausea (53 %), fatigue (45 %), and vomiting (43 %). Of 168 patients evaluable for response, 1 achieved a partial response, and stable disease was observed in 32 % of patients. CONCLUSIONS: Dovitinib capsules and tablets were bioequivalent, with a safety profile similar to that observed in other dovitinib studies of patients with heavily pretreated advanced solid tumors. PMID- 27681580 TI - Transcriptional regulatory mechanism of alcohol dehydrogenase 1-deficient mutant of rice for cell survival under complete submergence. AB - BACKGROUND: Rice is the only crop that germinates and elongates the coleoptile under complete submergence. It has been shown that alcohol dehydrogenase 1 (ADH1) deficient mutant of rice with reduced alcohol dehydrogenase activity (rad) and reduced ATP level, is viable with much reduced coleoptile elongation under such condition. To understand the altered transcriptional regulatory mechanism of this mutant, we aimed to establish possible relationships between gene expression and cis-regulatory information content. FINDINGS: We performed promoter analysis of the publicly available differentially expressed genes in ADH1 mutant. Our results revealed that a crosstalk between a number of key transcription factors (TFs) and different phytohormones altered transcriptional regulation leading to the survival of the mutant. Amongst the key TFs identified, we suggest potential involvement of MYB, bZIP, ARF and ERF as transcriptional activators and WRKY, ABI4 and MYC as transcriptional repressors of coleoptile elongation to maintain metabolite levels for the cell viability. Out of the repressors, WRKY TF is most likely playing a major role in the alteration of the physiological implications associated with the cell survival. CONCLUSIONS: Overall, our analysis provides a possible transcriptional regulatory mechanism underlying the survival of the rad mutant under complete submergence in an energy crisis condition and develops hypotheses for further experimental validation. PMID- 27681582 TI - Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels. AB - The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-beta1. Hepatocytes are not generally thought of as significant producers of GFs-this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function. PMID- 27681577 TI - Update on hypertrophic cardiomyopathy and a guide to the guidelines. AB - Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM. PMID- 27681584 TI - Dermatological emergencies: evolution from 2008 to 2014 and perspectives. AB - BACKGROUND: Our dermatological department includes a dermatological emergency unit (DEU) whose activity has grown in recent years. OBJECTIVES: An audit to characterize the activity of our DEU and its evolution in terms of medical demographics of the area. METHODS: We collected the following data from administrative services: number of patients consulting each year in the DEU and in the general emergency unit (GEU) of our hospital between 2008 and 2014; daily and seasonal activity of the DEU; occurrence of a second event in the department and proportion of patients from the DEU who were hospitalized and why. From the medical charts of a random sample of patients consulting in the first 15 days of January and August 2014, we studied the epidemiological profile, time to consultation and diagnoses. Data related to medical demographics (number of general practitioners and dermatologists) between 2007 and 2014 and projections were obtained. RESULTS: The activity in the DEU increased by 67% between 2008 and 2014 but remained stable in the GEU over the same period. The activity was higher on Mondays and in the summer (+30%). More than 15% of the patients were seen a second time in outpatient consultation; 1.2% were hospitalized. Infectious dermatosis was the main reason for consultation; seasonal-disease consultations were more frequent in the summer. Less than 40% of patients consulted in the first week after disease onset. Medical demographics continually decreased since 2007 in Paris and suburbs and will continue to decrease in the next years. CONCLUSION: The increasing activity of our DEU parallels the decrease in medical demographics in Paris. The proportion of patients hospitalized was low, in part due to specific healthcare networks implemented for some life-threatening dermatoses independent of the DEU. A better coordination between hospital and private practitioners for managing dermatologic emergencies, taking into account the decrease in medical demographics, is warranted. PMID- 27681583 TI - Patterns of Use, Acute Subjective Experiences, and Motivations for Using Synthetic Cathinones ("Bath Salts") in Recreational Users. AB - Given the variety and potential toxicity of synthetic cathinones, clinicians and educators would benefit from information about patterns of and motivations for use, frequency of psychosocial consequences, and experience of acute subjective effects. We administered a comprehensive, web-based survey to 104 recreational users of synthetic cathinones. Sixty percent of respondents consumed synthetic cathinones once or more per month, usually snorting or swallowing these drugs, typically at home, usually with others, customarily during the evening and nighttime hours, and often in combination with another drug such as alcohol or marijuana. Acute subjective effects attributed to synthetic cathinones were similar to those of other psychostimulants, including increased energy, rapid heartbeat, racing thoughts, difficulty sleeping, euphoria, decreased appetite, open-mindedness, and increased sex drive. Reported reasons for using synthetic cathinones included its stimulating effects, curiosity, substitution for another drug, and being at a party/music event. Respondents had experienced an average of six negative consequences of using synthetic cathinones during the previous year (e.g., tolerance, neglecting responsibilities, personality change). In combination with previously published investigations, these findings increase our understanding of the reported rationales and outcomes of recreational use of synthetic cathinones. PMID- 27681585 TI - The 3D future of wound healing. PMID- 27681586 TI - Impact of surgical wound dehiscence on health-related quality of life and mental health. AB - OBJECTIVE: To assess the impact of surgical wound dehiscence on health-related quality of life and mental health. Dehiscence of surgical wounds is a serious postoperative complication associated with high morbidity and mortality. METHOD: Sixty-one adult patients, who had undergone neurological, general, colorectal, orthopaedic, gynaecological, plastic, cardiovascular, urological or neurological surgery in a university hospital in Brazil, were assessed between 30 and 180 days after surgery. Twenty participants who achieved complete wound healing were allocated to the control group and 41 participants who developed surgical wound dehiscence were allocated to the dehiscence group. Patients unable to complete the questionnaires because of cognitive impairment and those who declined to participate or died were excluded from the study. Data were collected using a questionnaire assessing sociodemographic and clinical characteristics of participants; the Medical Outcomes Study 36-Item Short Form Health Survey (SF 36); and the Beck Depression Inventory (BDI). RESULTS: Surgical wound dehiscences were 0.5-30 cm in length, 0.5-7 cm in depth, and located in the arms, legs or trunk. There were significant between-group differences in mean scores on the physical functioning (p<0.01), role physical (p<0.01), social functioning (p=0.01), and bodily pain (p=0.01) dimensions of the SF-36. Participants with wound dehiscence reported significantly higher BDI scores (more depressive symptoms) than controls (p=0.01). CONCLUSION: Surgical wound dehiscence had a negative impact on the physical functioning, role physical, social functioning, and bodily pain dimensions of health-related quality of life and on mental health. DECLARATION OF INTEREST: No conflict of interest to declare. PMID- 27681587 TI - The role of resilience in rebuilding lives of injured veterans. AB - : The aim of this commentary is to discuss potential clinical implications of introducing resilience-building interventions into care for veterans who are living with a war wound. Some war veterans are expected to live with a wound upon discharge from an active military role and also to fit into civilian life. These lifestyle adjustments can tax the person's coping abilities and in that context may hinder successful adaptation. The experience of living with a wound or wounds, either acute or chronic, is connected to losses, including loss of mobility, loss of financial capacity (unable to work at times) and losses attached to changed social roles. Psychological stress is also a common experience for veterans returning to civilian life. Psychological stress is associated with impaired wound healing. Modern health practice is centred on symptom reduction and working with pathology, however, working with people's adaptive behaviours such as resilience has not been considered. Using the resilience model as a conceptual framework health-care professionals can engage with veterans towards resilience within the context of their personal experience of ill health. Using this contemporary framework for considering these aspects of care has the potential to facilitate resistance to stressors associated with being injured, possibly preventing quality-of-life impairments. DECLARATION OF INTEREST: There are no declarations of interest. PMID- 27681588 TI - Antibacterial properties and reduction of MRSA biofilm with a dressing combining polyabsorbent fibres and a silver matrix. AB - OBJECTIVE: This study was designed to evaluate the antibacterial activity of a wound dressing which combines polyacrylate fibres and a silver lipido-colloid matrix (UrgoClean Ag, silver polyabsorbent dressing), against biofilm of methicillin-resistant Staphylococcus aureus (MRSA). METHOD: Samples of silver polyabsorbent dressing and the neutral form of this dressing (UrgoClean) were applied to biofilms of MRSA formed on a collagen I-coated surface, cultured for 24 hours. Different exposure times were tested (1, 2, 4 and 7 days) without dressing change. The biofilm reduction was quantified by using culture methods and by confocal laser scanning microscopy experiments. RESULTS: The application of the silver polyabsorbent dressing resulted in a significant decrease of the biofilm population by a log reduction of 4.6, after 24 hours of exposure. Moreover, the antibiofilm activity was maintained for 7 days with reduction values up to 4 log (reduction of biofilm superior to 99.99%). The application of the neutral dressing also induced a significant reduction of the concentration of sessile cells after 1 day (about 0.90 log). The results obtained with this neutral form of the dressing showed that the polyacrylate fibres were able to exert a mechanical disruption of the biofilm architecture. CONCLUSION: These in vitro experiments demonstrated that silver polyabsorbent dressing was able to strongly reduce the biofilm of MRSA. The antibiofilm mechanism of this dressing can be explained by a dual action of the polyabsorbent fibres (based on ammonium polyacrylate polymer around an acrylic core) which induced a mechanical disruption of the biofilm matrix and/or a sequestration of sessile cells, and the diffusion of silver ions which produced bactericidal activity. DECLARATION OF INTEREST: This study was supported by Laboratoires Urgo (Dijon). P. Janod is an employee of Laboratoires Urgo. The company had no influence on the experimental design and the interpretation of the results. PMID- 27681589 TI - Effectiveness of hyaluronic acid and its derivatives on chronic wounds: a systematic review. AB - OBJECTIVE: Hyaluronic acid (HA) and its derivatives are used for chronic wounds, but evidence of their effectiveness remains unclear. The aim of this study was to provide more updated evidence for the effectiveness of HA (or its derivatives) compared with placebo or other agents for promoting healing in chronic wounds. METHOD: The Cochrane Central Register of Controlled Trials, MEDLINE via Ovid Online, CINAHL and the EMBASE via EBSCO host databases were searched. Drug companies and experts in wounds were also contacted. Randomised controlled trials of HA (or its derivatives) compared with control were eligible for inclusion. RESULTS: We identified nine randomised controlled trials involving 865 participants with chronic wounds were included in the review. The reporting for mixed arterial and venous ulcers seems to be better quality than that for venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). Studies provided little evidence regarding the claimed effects of HA or its derivaties on healing of chronic wounds. However, there is some evidence on their effectiveness for reducing pain intensity for mixed arterial and venous ulcers, which involved 255 patients (MD=-6.78 [95% CI: -11.10 to -2.46]). CONCLUSION: Evidence to guide decisions regarding the use of HA or its derivatives to promote wound healing is still limited. More good-quality randomised controlled trials are warranted. PMID- 27681590 TI - Casein kinase 1 is recruited to nuclear speckles by FAM83H and SON. AB - In some fibroblasts, casein kinase 1alpha (CK1alpha) is localized to nuclear speckles, which are sub-nuclear compartments supplying splicing factors, whereas it is recruited on keratin filaments in colorectal cancer cells such as DLD1 cells. In order to obtain a deeper understanding of why CK1alpha is localized to these different subcellular sites, we herein elucidated the mechanisms underlying its localization to nuclear speckles. CK1alpha and FAM83H were localized to nuclear speckles in RKO and WiDr colorectal cancer cells, which do not express simple epithelial keratins, and in DLD1 cells transfected with siRNAs for type I keratins. The localization of FAM83H to nuclear speckles was also detected in colorectal cancer cells with a poorly organized keratin cytoskeleton in colorectal cancer tissues. Using an interactome analysis of FAM83H, we identified SON, a protein present in nuclear speckles, as a scaffold protein to which FAM83H recruits CK1alpha. This result was supported by the knockdown of FAM83H or SON delocalizing CK1alpha from nuclear speckles. We also found that CK1delta and epsilon are localized to nuclear speckles in a FAM83H-dependent manner. These results suggest that CK1 is recruited to nuclear speckles by FAM83H and SON in the absence of an intact keratin cytoskeleton. PMID- 27681591 TI - Proteolytic activity in some freshwater animals and associated microflora in a wide pH range. AB - Proteolytic activity in some freshwater animals (crustacean plankton, sandhopper Amphipoda sp., larvae of chironomids Chironomus sp., oligochaetes Oligohaeta sp., dreissena Dreissena polymorpha, roach Rutilus rutilus heckelii, rudd Scardinius erythrophthalmus, ruff Acerina cernua, and monkey goby Neogobius fluviatilis) prevailing within the food of fishes of various ecological groups as well as in their associated microflora in a wide pH range was investigated. It has been shown that the optimum pH of proteases in the animals' whole organism varies: 6.0 for sandhopper; 8.0 for chironomid larvae, oligochaetes, monkey goby, and ruff; 8.0-9.0 for zooplankton; and 10.0 for roach and rudd. The optimum pH of associated microflora proteases is 6.0 for monkey goby; 7.0 for sandhopper and roach and ruff ; 8.0-9.0 for oligochaetes; 9.0 for zooplankton; and 10.0 for chironomid larvae and rudd. The compensatory role of food items and enteric microbiota proteases in digestive processes in fish of different ecological groups at low pH is discussed. PMID- 27681592 TI - mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib. AB - The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S. PMID- 27681593 TI - The Staphylococcus aureus Protein IsdH Inhibits Host Hemoglobin Scavenging to Promote Heme Acquisition by the Pathogen. AB - Hemolysis is a complication in septic infections with Staphylococcus aureus, which utilizes the released Hb as an iron source. S. aureus can acquire heme in vitro from hemoglobin (Hb) by a heme-sequestering mechanism that involves proteins from the S. aureus iron-regulated surface determinant (Isd) system. However, the host has its own mechanism to recapture the free Hb via haptoglobin (Hp) binding and uptake of Hb-Hp by the CD163 receptor in macrophages. It has so far remained unclear how the Isd system competes with this host iron recycling system in situ to obtain the important nutrient. By binding and uptake studies, we now show that the IsdH protein, which serves as an Hb receptor in the Isd system, directly interferes with the CD163-mediated clearance by binding the Hb Hp complex and inhibiting CD163 recognition. Analysis of truncated IsdH variants including one or more of three near iron transporter domains, IsdHN1, IsdHN2, and IsdHN3, revealed that Hb binding of IsdHN1 and IsdHN2 accounted for the high affinity for Hb-Hp complexes. The third near iron transporter domain, IsdHN3, exhibited redox-dependent heme extraction, when Hb in the Hb-Hp complex was in the oxidized met form but not in the reduced oxy form. IsdB, the other S. aureus Hb receptor, failed to extract heme from Hb-Hp, and it was a poor competitor for Hb-Hp binding to CD163. This indicates that Hb recognition by IsdH, but not by IsdB, sterically inhibits the receptor recognition of Hb-Hp. This function of IsdH may have an overall stimulatory effect on S. aureus heme acquisition and growth. PMID- 27681594 TI - Bone-protective Functions of Netrin 1 Protein. AB - Netrin 1 was initially identified as an axon guidance factor, and recent studies indicate that it inhibits chemokine-directed monocyte migration. Despite its importance as a neuroimmune guidance cue, the role of netrin 1 in osteoclasts is largely unknown. Here we detected high netrin 1 levels in the synovial fluid of rheumatoid arthritis patients. Netrin 1 is potently expressed in osteoblasts and synovial fibroblasts, and IL-17 robustly enhances netrin 1 expression in these cells. The binding of netrin 1 to its receptor UNC5b on osteoclasts resulted in activation of SHP1, which inhibited VAV3 phosphorylation and RAC1 activation. This significantly impaired the actin polymerization and fusion, but not the differentiation of osteoclast. Strikingly, netrin 1 treatment prevented bone erosion in an autoimmune arthritis model and age-related bone destruction. Therefore, the netrin 1-UNC5b axis is a novel therapeutic target for bone destructive diseases. PMID- 27681595 TI - Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport. AB - In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system that mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A. ift122 mutant larvae show unexpectedly mild phenotypes, compared with those of mutants defective in IFT-B. ift122 mutants exhibit a slow onset of progressive photoreceptor degeneration mainly after 7 days post-fertilization. ift122 mutant larvae also develop cystic kidney but not curly body, both of which are typically observed in various ciliary mutants. ift122 mutants display a loss of cilia in the inner ear hair cells and nasal pit epithelia. Loss of ift122 causes disorganization of outer segment discs. Ectopic accumulation of an IFT-B component, ift88, is observed in the ift122 mutant photoreceptor cilia. In addition, pulse-chase experiments using GFP-opsin fusion proteins revealed that ift122 is required for the efficient transport of opsin and the distal elongation of outer segments. These results show that IFT-A is essential for the efficient transport of outer segment proteins, including opsin, and for the survival of retinal photoreceptor cells, rendering the ift122 mutant a unique model for human retinal degenerative diseases. PMID- 27681596 TI - Small Molecule Inhibition of the Ubiquitin-specific Protease USP2 Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in Colorectal Cancer and Mantle Cell Lymphoma Models. AB - Deubiquitinases are important components of the protein degradation regulatory network. We report the discovery of ML364, a small molecule inhibitor of the deubiquitinase USP2 and its use to interrogate the biology of USP2 and its putative substrate cyclin D1. ML364 has an IC50 of 1.1 MUm in a biochemical assay using an internally quenched fluorescent di-ubiquitin substrate. Direct binding of ML364 to USP2 was demonstrated using microscale thermophoresis. ML364 induced an increase in cellular cyclin D1 degradation and caused cell cycle arrest as shown in Western blottings and flow cytometry assays utilizing both Mino and HCT116 cancer cell lines. ML364, and not the inactive analog 2, was antiproliferative in cancer cell lines. Consistent with the role of cyclin D1 in DNA damage response, ML364 also caused a decrease in homologous recombination mediated DNA repair. These effects by a small molecule inhibitor support a key role for USP2 as a regulator of cell cycle, DNA repair, and tumor cell growth. PMID- 27681599 TI - Physical, Textural, and Antioxidant Properties of Extruded Waxy Wheat Flour Snack Supplemented with Several Varieties of Bran. AB - Wheat represents a ubiquitous commodity and although industries valorize 10% of wheat bran, most of this antioxidant-rich byproduct gets fed to livestock. The objective of this study was to incorporate wheat bran into an extruded snack. Bran samples from hard red spring, soft white club cv. Bruehl, and purple wheat lines were added to cv. Waxy-Pen wheat flour (Triticum aestivum L.) at replacement concentrations of 0%, 12.5%, 25%, and 37.5% (w/w; n = 10). Extrudates were evaluated for antioxidant capacity, color, and physical properties. Results showed that high fiber concentrations altered several pasting properties, reduced expansion ratios (P < 0.0001), and created denser products (P < 0.0001), especially for white bran supplemented extrudates. Purple bran supplemented extrudates produced harder products compared to white and red bran treatments (P < 0.0001). Extrudates produced with 37.5% (w/w) of each bran variety absorbed more water than the control with no added bran. The oxygen radical absorption capacity assay, expressed as Trolox Equivalents, showed that extrudates made with addition of red (37.5%) and purple (37.5%) bran had higher values compared to the other treatments; the control, red, and white bran treatments had less antioxidant activity after extrusion (P < 0.0001) compared to purple bran supplemented extrudates. Purple and red brans may serve as viable functional ingredients in extruded foods given their higher antioxidant activities. Future studies could evaluate how bran variety and concentration, extruded shape, and flavor influence consumer acceptance. PMID- 27681600 TI - Early surgical treatment of retinal hemangioblastomas. AB - PURPOSE: To evaluate the clinical course after early surgical treatment with excision of retinal hemangioblastomas (RHs) before development of major complications. METHODS: Interventional case series of four eyes (four patients) with a peripheral RH that had not yet been treated by laser or cryotherapy prior to surgery. All eyes underwent 23-gauge vitrectomy with lesion excision. One patient underwent ligation of the feeder vessel prior to lesion excision. Best corrected visual acuity and clinical course were assessed during a follow-up period of at least 4 years. RESULTS: Four patients (mean age 27.3 years; range 19 32) were included, of whom two had von Hippel-Lindau syndrome. Visual acuity improved in three patients (mean 4.8 lines; range 3-10) and remained stable at 0.0 logMAR in one patient. There were no intraoperative complications. Postoperative complications included transient mild vitreous haemorrhage (n = 2), and local epiretinal membrane formation at the excision location (n = 1). At 4 years postoperatively, there were no long-term complications. There was one case of a new lesion, which was effectively treated with laser. CONCLUSION: Vitrectomy with RH excision seems to be an effective approach for larger RHs and could be considered an early treatment option in selected cases. Postoperative complications were limited in scope of this case series. Important points to consider during vitrectomy are effective closure of feeder and draining vessels as well as complete removal of posterior hyaloid and epiretinal membranes in order to avoid postoperative vitreous haemorrhage and proliferative vitreoretinopathy. PMID- 27681597 TI - Deep Mutational Scans as a Guide to Engineering High Affinity T Cell Receptor Interactions with Peptide-bound Major Histocompatibility Complex. AB - Proteins are often engineered to have higher affinity for their ligands to achieve therapeutic benefit. For example, many studies have used phage or yeast display libraries of mutants within complementarity-determining regions to affinity mature antibodies and T cell receptors (TCRs). However, these approaches do not allow rapid assessment or evolution across the entire interface. By combining directed evolution with deep sequencing, it is now possible to generate sequence fitness landscapes that survey the impact of every amino acid substitution across the entire protein-protein interface. Here we used the results of deep mutational scans of a TCR-peptide-MHC interaction to guide mutational strategies. The approach yielded stable TCRs with affinity increases of >200-fold. The substitutions with the greatest enrichments based on the deep sequencing were validated to have higher affinity and could be combined to yield additional improvements. We also conducted in silico binding analyses for every substitution to compare them with the fitness landscape. Computational modeling did not effectively predict the impacts of mutations distal to the interface and did not account for yeast display results that depended on combinations of affinity and protein stability. However, computation accurately predicted affinity changes for mutations within or near the interface, highlighting the complementary strengths of computational modeling and yeast surface display coupled with deep mutational scanning for engineering high affinity TCRs. PMID- 27681598 TI - Heparin Binds Lamprey Angiotensinogen and Promotes Thrombin Inhibition through a Template Mechanism. AB - Lamprey angiotensinogen (l-ANT) is a hormone carrier in the regulation of blood pressure, but it is also a heparin-dependent thrombin inhibitor in lamprey blood coagulation system. The detailed mechanisms on how angiotensin is carried by l ANT and how heparin binds l-ANT and mediates thrombin inhibition are unclear. Here we have solved the crystal structure of cleaved l-ANT at 2.7 A resolution and characterized its properties in heparin binding and protease inhibition. The structure reveals that l-ANT has a conserved serpin fold with a labile N-terminal angiotensin peptide and undergoes a typical stressed-to-relaxed conformational change when the reactive center loop is cleaved. Heparin binds l-ANT tightly with a dissociation constant of ~10 nm involving ~8 monosaccharides and ~6 ionic interactions. The heparin binding site is located in an extensive positively charged surface area around helix D involving residues Lys-148, Lys-151, Arg-155, and Arg-380. Although l-ANT by itself is a poor thrombin inhibitor with a second order rate constant of 500 m-1 s-1, its interaction with thrombin is accelerated 90-fold by high molecular weight heparin following a bell-shaped dose-dependent curve. Short heparin chains of 6-20 monosaccharide units are insufficient to promote thrombin inhibition. Furthermore, an l-ANT mutant with the P1 Ile mutated to Arg inhibits thrombin nearly 1500-fold faster than the wild type, which is further accelerated by high molecular weight heparin. Taken together, these results suggest that heparin binds l-ANT at a conserved heparin binding site around helix D and promotes the interaction between l-ANT and thrombin through a template mechanism conserved in vertebrates. PMID- 27681601 TI - The effect of an educational pre-operative DVD on parents' and children's outcomes after a same-day surgery: a randomized controlled trial. AB - AIMS: To examine the effect of a pre-operative DVD on parents' knowledge, participation and anxiety and on children's distress, pain, analgesic requirements and length of recovery after same-day surgery. BACKGROUND: Very few parents are adequately prepared to participate in their child's care during a same-day surgery. An educational DVD was developed to educate parents on how to actively support their child in the recovery room. DESIGN: Single-blind, post test randomized controlled trial. Study is registered at ClinicalTrials.gov NCT02766452. METHODS: Between September 2011-September 2012, 123 parent-child dyads where the child underwent an ENT or dental same-day surgery were recruited in a Canadian paediatric hospital. Dyads were randomly assigned to either the intervention (DVD and standard preparation) or control group (standard preparation). Parents and children were videotaped in the recovery room where parental participation and anxiety and children's distress were measured. Data on parents' knowledge, children's postoperative pain, analgesic requirements and length of recovery were measured. Independent and paired t-tests, chi square and repeated measures anova were used to analyse the data. RESULTS: Parents in the intervention group gained greater knowledge of and used more positive reinforcement and distraction and relaxation methods than those in the control group. Children's postoperative pain in the day-care surgery unit was significantly lower among the intervention group compared with the control group. CONCLUSION: A pre-operative DVD can increase parents' participation in the recovery room and decrease children's postoperative pain. PMID- 27681602 TI - A novel machine learning-enabled framework for instantaneous heart rate monitoring from motion-artifact-corrupted electrocardiogram signals. AB - This paper proposes a novel machine learning-enabled framework to robustly monitor the instantaneous heart rate (IHR) from wrist-electrocardiography (ECG) signals continuously and heavily corrupted by random motion artifacts in wearable applications. The framework includes two stages, i.e. heartbeat identification and refinement, respectively. In the first stage, an adaptive threshold-based auto-segmentation approach is proposed to select out heartbeat candidates, including the real heartbeats and large amounts of motion-artifact-induced interferential spikes. Then twenty-six features are extracted for each candidate in time, spatial, frequency and statistical domains, and evaluated by a spare support vector machine (SVM) to select out ten critical features which can effectively reveal residual heartbeat information. Afterwards, an SVM model, created on the training data using the selected feature set, is applied to find high confident heartbeats from a large number of candidates in the testing data. In the second stage, the SVM classification results are further refined by two steps: (1) a rule-based classifier with two attributes named 'continuity check' and 'locality check' for outlier (false positives) removal, and (2) a heartbeat interpolation strategy for missing-heartbeat (false negatives) recovery. The framework is evaluated on a wrist-ECG dataset acquired by a semi-customized platform and also a public dataset. When the signal-to-noise ratio is as low as 7 dB, the mean absolute error of the estimated IHR is 1.4 beats per minute (BPM) and the root mean square error is 6.5 BPM. The proposed framework greatly outperforms well-established approaches, demonstrating that it can effectively identify the heartbeats from ECG signals continuously corrupted by intense motion artifacts and robustly estimate the IHR. This study is expected to contribute to robust long-term wearable IHR monitoring for pervasive heart health and fitness management. PMID- 27681603 TI - Some practical considerations in three-arm non-inferiority trial design. AB - Non-inferiority trials aim to demonstrate whether an experimental therapy is not unacceptably worse than an active reference therapy already in use. When applicable, a three-arm non-inferiority trial, including an experiment therapy, an active reference therapy, and a placebo, is often recommended to assess assay sensitivity and internal validity of a trial. In this paper, we share some practical considerations based on our experience from a phase III three-arm non inferiority trial. First, we discuss the determination of the total sample size and its optimal allocation based on the overall power of the non-inferiority testing procedure and provide ready-to-use R code for implementation. Second, we consider the non-inferiority goal of 'capturing all possibilities' and show that it naturally corresponds to a simple two-step testing procedure. Finally, using this two-step non-inferiority testing procedure as an example, we compare extensively commonly used frequentist p -value methods with the Bayesian posterior probability approach. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27681604 TI - Sixty seconds on . . . medical philanthropists. PMID- 27681605 TI - Small artery mechanobiology: Roles of cellular and non-cellular elements. AB - Small arteries and their component cellular and non-cellular elements are continually subjected to, and interact with, mechanical forces. Such interactions are key in both short- and long-term adaptation of the structure and function of the microcirculation to its local environment and metabolic requirements. Following this brief introduction is a series of papers presented as a symposium (Small Artery Mechanobiology: Roles of Cellular and Non-Cellular Elements) at the World Congress for Microcirculation, Kyoto 2015. PMID- 27681608 TI - Poststroke Rehabilitation: Assessment, Referral, and Patient Management. AB - This Quick Reference Guide for Clinicians contains highlights from Post-Stroke Rehabilitation, Clinical Practice Guideline No. 16, which was developed by a multidisciplinary, private-sector panel comprised of health care professionals and a consumer representative. The Quick Reference Guide for Clinicians is an example of how a clinician might implement the panel's findings and recommendations on the overall management of stroke patients who need poststroke rehabilitation programs or services before returning to a family or other living environment. Topics include medical management of patients, systematic assessment and evaluation of patients throughout acute care and rehabilitation, referring patients to appropriate rehabilitation programs, managing the rehabilitation process, discharging patients from rehabilitation programs, and reintegrating patients into family and community environments. PMID- 27681609 TI - Application of Motor Learning Principles to the Stroke Population. AB - The physical rehabilitation of patients with stroke is shifting from a medical model of treating neurophysiological impairment to an educational model that emphasizes the reeducation of patients in motor tasks. This greater focus on patient learning requires knowledge not only in how to assist patients in the restoration of efficient movement patterns, but also in how to help patients learn to create and modify movement strategies to solve the functional problems they encounter in daily tasks. This article provides an overview of principles to be considered when attempting to optimize the motor learning of stroke patients. A model of motor learning is presented, followed by a discussion of contemporary research and clinical issues in the areas of information processing and practice. It is proposed that only through the combination of clinical research and critical introspection of our treatment practices can we gain a more complete insight to the motor learning behavior of stroke patients. PMID- 27681606 TI - Enrichment of hydroxylated C24- and C26-acyl-chain sphingolipids mediates PIN2 apical sorting at trans-Golgi network subdomains. AB - The post-Golgi compartment trans-Golgi Network (TGN) is a central hub divided into multiple subdomains hosting distinct trafficking pathways, including polar delivery to apical membrane. Lipids such as sphingolipids and sterols have been implicated in polar trafficking from the TGN but the underlying mechanisms linking lipid composition to functional polar sorting at TGN subdomains remain unknown. Here we demonstrate that sphingolipids with alpha-hydroxylated acyl chains of at least 24 carbon atoms are enriched in secretory vesicle subdomains of the TGN and are critical for de novo polar secretory sorting of the auxin carrier PIN2 to apical membrane of Arabidopsis root epithelial cells. We show that sphingolipid acyl-chain length influences the morphology and interconnections of TGN-associated secretory vesicles. Our results uncover that the sphingolipids acyl-chain length links lipid composition of TGN subdomains with polar secretory trafficking of PIN2 to apical membrane of polarized epithelial cells. PMID- 27681610 TI - Linguistic-Specific Sentence Production Treatment for Agrammatic Aphasia. AB - This article describes an approach to treatment of agrammatic aphasic individuals' sentence production deficits. In this linguistic-specific sentence production treatment, sentences selected for treatment and the treatment itself are control led for their lexical and syntactic properties. Results derived from a series of studies using this approach have shown successful outcomes of treatment. Improved production of sentences targeted for training and generalization to untrained sentences that are linguistically similar to those trained have resulted from treatment. In addition, improvements in sentence production in discourse tasks have been noted. An overview of the theoretical foundation of linguistic-specific sentence production treatment, the results of our experiments investigating its efficacy, and clinical protocols is provided. PMID- 27681611 TI - Cardiac Complications during Inpatient Stroke Rehabilitation. PMID- 27681607 TI - Bacteroides intestinalis DSM 17393, a member of the human colonic microbiome, upregulates multiple endoxylanases during growth on xylan. AB - Many human diets contain arabinoxylan, and the ease of genome sequencing coupled with reduced cost have led to unraveling the arsenal of genes utilized by the colonic Bacteroidetes to depolymerize this polysaccharide. The colonic Bacteroidetes with potential to ferment arabinoxylans include Bacteroides intestinalis. In this study, we analyzed the hydrolytic activities of members of a xylan degradation cluster encoded on the genome of Bacteroides intestinalis DSM 17393. Here, it is demonstrated that a cocktail of the xylanolytic enzymes completely hydrolyze arabinoxylans found in human diets. We show that this bacterium and relatives have evolved and secrete a unique bifunctional endoxylanase/arabinofuranosidase in the same polypeptide. The bifunctional enzyme and other secreted enzymes attack the polysaccharides extracellularly to remove the side-chains, exposing the xylan backbone for cleavage to xylo oligosaccharides and xylose. These end products are transported into the cell where a beta-xylosidase cleaves the oligosaccharides to fermentable sugars. While our experiments focused on B. intestinalis, it is likely that the extracellular enzymes also release nutrients to members of the colonic microbial community that practice cross-feeding. The presence of the genes characterized in this study in other colonic Bacteroidetes suggests a conserved strategy for energy acquisition from arabinoxylan, a component of human diets. PMID- 27681612 TI - Computer-Mediated Information Technology for Practitioners. PMID- 27681614 TI - Letters to the Editors. PMID- 27681613 TI - From the Editor. PMID- 27681616 TI - Two subdivisions of macaque LIP process visual-oculomotor information differently. AB - Although the cerebral cortex is thought to be composed of functionally distinct areas, the actual parcellation of area and assignment of function are still highly controversial. An example is the much-studied lateral intraparietal cortex (LIP). Despite the general agreement that LIP plays an important role in visual oculomotor transformation, it remains unclear whether the area is primary sensory or motor-related (the attention-intention debate). Although LIP has been considered as a functionally unitary area, its dorsal (LIPd) and ventral (LIPv) parts differ in local morphology and long-distance connectivity. In particular, LIPv has much stronger connections with two oculomotor centers, the frontal eye field and the deep layers of the superior colliculus, than does LIPd. Such anatomical distinctions imply that compared with LIPd, LIPv might be more involved in oculomotor processing. We tested this hypothesis physiologically with a memory saccade task and a gap saccade task. We found that LIP neurons with persistent memory activities in memory saccade are primarily provoked either by visual stimulation (vision-related) or by both visual and saccadic events (vision saccade-related) in gap saccade. The distribution changes from predominantly vision-related to predominantly vision-saccade-related as the recording depth increases along the dorsal-ventral dimension. Consistently, the simultaneously recorded local field potential also changes from visual evoked to saccade evoked. Finally, local injection of muscimol (GABA agonist) in LIPv, but not in LIPd, dramatically decreases the proportion of express saccades. With these results, we conclude that LIPd and LIPv are more involved in visual and visual-saccadic processing, respectively. PMID- 27681615 TI - Repression of p63 and induction of EMT by mutant Ras in mammary epithelial cells. AB - The p53-related transcription factor p63 is required for maintenance of epithelial cell differentiation. We found that activated forms of the Harvey Rat Sarcoma Virus GTPase (H-RAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) oncogenes strongly repress expression of ?Np63alpha, the predominant p63 isoform in basal mammary epithelial cells. This regulation occurs at the transcriptional level, and a short region of the ?Np63 promoter is sufficient for repression induced by H-RasV12. The suppression of ?Np63alpha expression by these oncogenes concomitantly leads to an epithelial-to mesenchymal transition (EMT). In addition, the depletion of ?Np63alpha alone is sufficient to induce EMT. Both H-RasV12 expression and ?Np63alpha depletion induce individual cell invasion in a 3D collagen gel in vitro system, thereby demonstrating how Ras can drive the mammary epithelial cell state toward greater invasive ability. Together, these results suggest a pathway by which RAS and PIK3CA oncogenes induce EMT through regulation of ?Np63alpha. PMID- 27681618 TI - A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii. AB - The Gram-negative bacterial outer membrane fortifies the cell against environmental toxins including antibiotics. Unique glycolipids called lipopolysaccharide/lipooligosaccharide (LPS/LOS) are enriched in the cell-surface monolayer of the outer membrane and promote antimicrobial resistance. Colistin, which targets the lipid A domain of LPS/LOS to lyse the cell, is the last-line treatment for multidrug-resistant Gram-negative infections. Lipid A is essential for the survival of most Gram-negative bacteria, but colistin-resistant Acinetobacter baumannii lacking lipid A were isolated after colistin exposure. Previously, strain ATCC 19606 was the only A. baumannii strain demonstrated to subsist without lipid A. Here, we show that other A. baumannii strains can also survive without lipid A, but some cannot, affording a unique model to study endotoxin essentiality. We assessed the capacity of 15 clinical A. baumannii isolates including 9 recent clinical isolates to develop colistin resistance through inactivation of the lipid A biosynthetic pathway, the products of which assemble the LOS precursor. Our investigation determined that expression of the well-conserved penicillin-binding protein (PBP) 1A, prevented LOS-deficient colony isolation. The glycosyltransferase activity of PBP1A, which aids in the polymerization of the peptidoglycan cell wall, was lethal to LOS-deficient A. baumannii Global transcriptomic analysis of a PBP1A-deficient mutant and four LOS deficient A. baumannii strains showed a concomitant increase in transcription of lipoproteins and their transporters. Examination of the LOS-deficient A. baumannii cell surface demonstrated that specific lipoproteins were overexpressed and decorated the cell surface, potentially compensating for LOS removal. This work expands our knowledge of lipid A essentiality and elucidates a drug resistance mechanism. PMID- 27681619 TI - Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood. AB - The T-cell receptor (TCR) is required for maturation and function of regulatory T cells (Tregs), but the ligand specificities of Tregs outside the context of transgenic TCRs are largely unknown. Using peptide-MHC tetramers, we isolated rare specific Foxp3+ cells directly ex vivo from adult peripheral blood and defined their frequency and phenotype. We find that a proportion of circulating Tregs recognize foreign antigens and the frequency of these cells are similar to that of self-reactive Tregs in the absence of cognate infection. In contrast, the frequencies of Tregs that recognize some common microbial antigens are significantly reduced in the blood of most adults. Exposure to peripheral antigens likely has a major influence on the balance between Tregs and conventional T-cell subsets because a larger proportion of flu-specific T cells has a regulatory cell phenotype in the cord blood. Consistent with this finding, we show that lymphocytic choriomeningitis virus infection can directly modulate the ratio of virus-specific effectors and Tregs in mice. The resulting change in the balance within an antigen-specific T-cell population further correlates with the magnitude of effector response and the chronicity of infection. Taken together, our data highlight the importance of antigen specificity in the functional dynamics of the T-cell repertoire. Each specific population of CD4+ T cells in human peripheral blood contains a subset of Tregs at birth, but the balance between regulatory and effector subsets changes in response to peripheral antigen exposure and this could impact the robustness of antipathogen immunity. PMID- 27681617 TI - Mutant PFN1 causes ALS phenotypes and progressive motor neuron degeneration in mice by a gain of toxicity. AB - Mutations in the profilin 1 (PFN1) gene cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease caused by the loss of motor neurons leading to paralysis and eventually death. PFN1 is a small actin-binding protein that promotes formin-based actin polymerization and regulates numerous cellular functions, but how the mutations in PFN1 cause ALS is unclear. To investigate this problem, we have generated transgenic mice expressing either the ALS associated mutant (C71G) or wild-type protein. Here, we report that mice expressing the mutant, but not the wild-type, protein had relentless progression of motor neuron loss with concomitant progressive muscle weakness ending in paralysis and death. Furthermore, mutant, but not wild-type, PFN1 forms insoluble aggregates, disrupts cytoskeletal structure, and elevates ubiquitin and p62/SQSTM levels in motor neurons. Unexpectedly, the acceleration of motor neuron degeneration precedes the accumulation of mutant PFN1 aggregates. These results suggest that although mutant PFN1 aggregation may contribute to neurodegeneration, it does not trigger its onset. Importantly, these experiments establish a progressive disease model that can contribute toward identifying the mechanisms of ALS pathogenesis and the development of therapeutic treatments. PMID- 27681620 TI - Structure-guided enzymology of the lipid A acyltransferase LpxM reveals a dual activity mechanism. AB - Gram-negative bacteria possess a characteristic outer membrane, of which the lipid A constituent elicits a strong host immune response through the Toll-like receptor 4 complex, and acts as a component of the permeability barrier to prevent uptake of bactericidal compounds. Lipid A species comprise the bulk of the outer leaflet of the outer membrane and are produced through a multistep biosynthetic pathway conserved in most Gram-negative bacteria. The final steps in this pathway involve the secondary acylation of lipid A precursors. These are catalyzed by members of a superfamily of enzymes known as lysophospholipid acyltransferases (LPLATs), which are present in all domains of life and play important roles in diverse biological processes. To date, characterization of this clinically important class of enzymes has been limited by a lack of structural information and the availability of only low-throughput biochemical assays. In this work, we present the structure of the bacterial LPLAT protein LpxM, and we describe a high-throughput, label-free mass spectrometric assay to characterize acyltransferase enzymatic activity. Using our structure and assay, we identify an LPLAT thioesterase activity, and we provide experimental evidence to support an ordered-binding and "reset" mechanistic model for LpxM function. This work enables the interrogation of other bacterial acyltransferases' structure-mechanism relationships, and the assay described herein provides a foundation for quantitatively characterizing the enzymology of any number of clinically relevant LPLAT proteins. PMID- 27681621 TI - A ring-shaped conduit connects the mother cell and forespore during sporulation in Bacillus subtilis. AB - During spore formation in Bacillus subtilis a transenvelope complex is assembled across the double membrane that separates the mother cell and forespore. This complex (called the "A-Q complex") is required to maintain forespore development and is composed of proteins with remote homology to components of type II, III, and IV secretion systems found in Gram-negative bacteria. Here, we show that one of these proteins, SpoIIIAG, which has remote homology to ring-forming proteins found in type III secretion systems, assembles into an oligomeric ring in the periplasmic-like space between the two membranes. Three-dimensional reconstruction of images generated by cryo-electron microscopy indicates that the SpoIIIAG ring has a cup-and-saucer architecture with a 6-nm central pore. Structural modeling of SpoIIIAG generated a 24-member ring with dimensions similar to those of the EM-derived saucer. Point mutations in the predicted oligomeric interface disrupted ring formation in vitro and impaired forespore gene expression and efficient spore formation in vivo. Taken together, our data provide strong support for the model in which the A-Q transenvelope complex contains a conduit that connects the mother cell and forespore. We propose that a set of stacked rings spans the intermembrane space, as has been found for type III secretion systems. PMID- 27681622 TI - Suppression of NF-kappaB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. AB - Osteoarthritis (OA) is a major cause of disability and morbidity in the aging population. Joint injury leads to cartilage damage, a known determinant for subsequent development of posttraumatic OA, which accounts for 12% of all OA. Understanding the early molecular and cellular responses postinjury may provide targets for therapeutic interventions that limit articular degeneration. Using a murine model of controlled knee joint impact injury that allows the examination of cartilage responses to injury at specific time points, we show that intraarticular delivery of a peptidic nanoparticle complexed to NF-kappaB siRNA significantly reduces early chondrocyte apoptosis and reactive synovitis. Our data suggest that NF-kappaB siRNA nanotherapy maintains cartilage homeostasis by enhancing AMPK signaling while suppressing mTORC1 and Wnt/beta-catenin activity. These findings delineate an extensive crosstalk between NF-kappaB and signaling pathways that govern cartilage responses postinjury and suggest that delivery of NF-kappaB siRNA nanotherapy to attenuate early inflammation may limit the chronic consequences of joint injury. Therapeutic benefits of siRNA nanotherapy may also apply to primary OA in which NF-kappaB activation mediates chondrocyte catabolic responses. Additionally, a critical barrier to the successful development of OA treatment includes ineffective delivery of therapeutic agents to the resident chondrocytes in the avascular cartilage. Here, we show that the peptide-siRNA nanocomplexes are nonimmunogenic, are freely and deeply penetrant to human OA cartilage, and persist in chondrocyte lacunae for at least 2 wk. The peptide siRNA platform thus provides a clinically relevant and promising approach to overcoming the obstacles of drug delivery to the highly inaccessible chondrocytes. PMID- 27681623 TI - Concomitant emergence of the antisense protein gene of HIV-1 and of the pandemic. AB - Recent experiments provide sound arguments in favor of the in vivo expression of the AntiSense Protein (ASP) of HIV-1. This putative protein is encoded on the antisense strand of the provirus genome and entirely overlapped by the env gene with reading frame -2. The existence of ASP was suggested in 1988, but is still controversial, and its function has yet to be determined. We used a large dataset of ~23,000 HIV-1 and SIV sequences to study the origin, evolution, and conservation of the asp gene. We found that the ASP ORF is specific to group M of HIV-1, which is responsible for the human pandemic. Moreover, the correlation between the presence of asp and the prevalence of HIV-1 groups and M subtypes appeared to be statistically significant. We then looked for evidence of selection pressure acting on asp Using computer simulations, we showed that the conservation of the ASP ORF in the group M could not be due to chance. Standard methods were ineffective in disentangling the two selection pressures imposed by both the Env and ASP proteins-an expected outcome with overlaps in frame -2. We thus developed a method based on careful evolutionary analysis of the presence/absence of stop codons, revealing that ASP does impose significant selection pressure. All of these results support the idea that asp is the 10th gene of HIV-1 group M and indicate a correlation with the spread of the pandemic. PMID- 27681625 TI - Witnessing entanglement without entanglement witness operators. AB - Quantum mechanics predicts the existence of correlations between composite systems that, although puzzling to our physical intuition, enable technologies not accessible in a classical world. Notwithstanding, there is still no efficient general method to theoretically quantify and experimentally detect entanglement of many qubits. Here we propose to detect entanglement by measuring the statistical response of a quantum system to an arbitrary nonlocal parametric evolution. We witness entanglement without relying on the tomographic reconstruction of the quantum state, or the realization of witness operators. The protocol requires two collective settings for any number of parties and is robust against noise and decoherence occurring after the implementation of the parametric transformation. To illustrate its user friendliness we demonstrate multipartite entanglement in different experiments with ions and photons by analyzing published data on fidelity visibilities and variances of collective observables. PMID- 27681624 TI - MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis. AB - The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment. PMID- 27681626 TI - Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells. AB - Norovirus is the leading cause of acute gastroenteritis worldwide. Since the discovery of human norovirus (HuNoV), an efficient and reproducible norovirus replication system has not been established in cultured cells. Although limited amounts of virus particles can be produced when the HuNoV genome is directly transfected into cells, the HuNoV cycle of infection has not been successfully reproduced in any currently available cell-culture system. Those results imply that the identification of a functional cell-surface receptor for norovirus might be the key to establishing a norovirus culture system. Using a genome-wide CRISPR/Cas9 guide RNA library, we identified murine CD300lf and CD300ld as functional receptors for murine norovirus (MNV). The treatment of susceptible cells with polyclonal antibody against CD300lf significantly reduced the production of viral progeny. Additionally, ectopic CD300lf expression in nonsusceptible cell lines derived from other animal species enabled MNV infection and progeny production, suggesting that CD300lf has potential for dictating MNV host tropism. Furthermore, CD300ld, which has an amino acid sequence in the N terminal region of its extracellular domain that is highly homologous to that of CD300lf, also functions as a receptor for MNV. Our results indicate that direct interaction of MNV with two cell-surface molecules, CD300lf and CD300ld, dictates permissive noroviral infection. PMID- 27681628 TI - Innovation network. AB - Technological progress builds upon itself, with the expansion of invention in one domain propelling future work in linked fields. Our analysis uses 1.8 million US patents and their citation properties to map the innovation network and its strength. Past innovation network structures are calculated using citation patterns across technology classes during 1975-1994. The interaction of this preexisting network structure with patent growth in upstream technology fields has strong predictive power on future innovation after 1995. This pattern is consistent with the idea that when there is more past upstream innovation for a particular technology class to build on, then that technology class innovates more. PMID- 27681627 TI - Atomic lattice disorder in charge-density-wave phases of exfoliated dichalcogenides (1T-TaS2). AB - Charge-density waves (CDWs) and their concomitant periodic lattice distortions (PLDs) govern the electronic properties in several layered transition-metal dichalcogenides. In particular, 1T-TaS2 undergoes a metal-to-insulator phase transition as the PLD becomes commensurate with the crystal lattice. Here we directly image PLDs of the nearly commensurate (NC) and commensurate (C) phases in thin, exfoliated 1T-TaS2 using atomic resolution scanning transmission electron microscopy at room and cryogenic temperature. At low temperatures, we observe commensurate PLD superstructures, suggesting ordering of the CDWs both in and out-of-plane. In addition, we discover stacking transitions in the atomic lattice that occur via one-bond-length shifts. Interestingly, the NC PLDs exist inside both the stacking domains and their boundaries. Transitions in stacking order are expected to create fractional shifts in the CDW between layers and may be another route to manipulate electronic phases in layered dichalcogenides. PMID- 27681630 TI - Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel. AB - The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a channel with an array of membrane valves along its length, which allows mimicking active contractions of the colonic wall. Repeated contraction is shown to be crucial in maintaining a steady-state bacterial population in the device despite strong flow along the channel that would otherwise cause bacterial washout. Depending on the flow rate and the frequency of contractions, the bacterial density profile exhibits varying spatial dependencies. For a synthetic cross-feeding community, the species abundance ratio is also strongly affected by mixing and flow along the length of the device. Complex mixing dynamics due to contractions is described well by an effective diffusion term. Bacterial dynamics is captured by a simple reaction-diffusion model without adjustable parameters. Our results suggest that flow and mixing play a major role in shaping the microbiota of the colon. PMID- 27681632 TI - Bursts of activity in collective cell migration. AB - Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems. PMID- 27681635 TI - Li-Ion Conductivity and Phase Stability of Ca-Doped LiBH4 under High Pressure. AB - The effect of Ca doping on the Li-ion conductivity and phase stability of the rock-salt-type LiBH4 phase emerging under high pressures in the range of gigapascals has been investigated. In situ electrochemical measurements under high pressure were performed using a cubic-anvil-type apparatus. Ca doping drastically enhanced the ionic conductivity of the rock-salt-type phase: the ionic conductivity of undoped and 5 mol %Ca-doped LiBH4 was 2.2 * 10-4 and 1.4 * 10-2 S.cm-1 under 4.0 GPa at 220 degrees C, respectively. The activation volume of LiBH4-5 mol %Ca(BH4)2, at 3.2 cm3.mol-1, was comparable to that of other fast ionic conductors, such as lithium titanate and NASICONs. Moreover, Ca-doped LiBH4 showed lithium plating-stripping behavior in a cyclic voltammogram. These results indicate that the conductivity enhancement by Ca doping can be attributed to the formation of a LiBH4-Ca(BH4)2 solid solution; however, the solid solution decomposed into the orthorhombic LiBH4 phase and the orthorhombic Ca(BH4)2 phase after unloading the high pressure. PMID- 27681629 TI - Early somatic mosaicism is a rare cause of long-QT syndrome. AB - Somatic mosaicism, the occurrence and propagation of genetic variation in cell lineages after fertilization, is increasingly recognized to play a causal role in a variety of human diseases. We investigated the case of life-threatening arrhythmia in a 10-day-old infant with long QT syndrome (LQTS). Rapid genome sequencing suggested a variant in the sodium channel NaV1.5 encoded by SCN5A, NM_000335:c.5284G > T predicting p.(V1762L), but read depth was insufficient to be diagnostic. Exome sequencing of the trio confirmed read ratios inconsistent with Mendelian inheritance only in the proband. Genotyping of single circulating leukocytes demonstrated the mutation in the genomes of 8% of patient cells, and RNA sequencing of cardiac tissue from the infant confirmed the expression of the mutant allele at mosaic ratios. Heterologous expression of the mutant channel revealed significantly delayed sodium current with a dominant negative effect. To investigate the mechanism by which mosaicism might cause arrhythmia, we built a finite element simulation model incorporating Purkinje fiber activation. This model confirmed the pathogenic consequences of cardiac cellular mosaicism and, under the presenting conditions of this case, recapitulated 2:1 AV block and arrhythmia. To investigate the extent to which mosaicism might explain undiagnosed arrhythmia, we studied 7,500 affected probands undergoing commercial gene-panel testing. Four individuals with pathogenic variants arising from early somatic mutation events were found. Here we establish cardiac mosaicism as a causal mechanism for LQTS and present methods by which the general phenomenon, likely to be relevant for all genetic diseases, can be detected through single cell analysis and next-generation sequencing. PMID- 27681634 TI - Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in Neurospora crassa. AB - DNA methylation, heterochromatin protein 1 (HP1), histone H3 lysine 9 (H3K9) methylation, histone deacetylation, and highly repeated sequences are prototypical heterochromatic features, but their interrelationships are not fully understood. Prior work showed that H3K9 methylation directs DNA methylation and histone deacetylation via HP1 in Neurospora crassa and that the histone deacetylase complex HCHC is required for proper DNA methylation. The complex consists of the chromodomain proteins HP1 and chromodomain protein 2 (CDP-2), the histone deacetylase HDA-1, and the AT-hook motif protein CDP-2/HDA-1-associated protein (CHAP). We show that the complex is required for proper chromosome segregation, dissect its function, and characterize interactions among its components. Our analyses revealed the existence of an HP1-based DNA methylation pathway independent of its chromodomain. The pathway partially depends on CHAP but not on the CDP-2 chromodomain. CDP-2 serves as a bridge between the recognition of H3K9 trimethylation (H3K9me3) by HP1 and the histone deacetylase activity of HDA-1. CHAP is also critical for HDA-1 localization to heterochromatin. Specifically, the CHAP zinc finger interacts directly with the HDA-1 argonaute-binding protein 2 (Arb2) domain, and the CHAP AT-hook motifs recognize heterochromatic regions by binding to AT-rich DNA. Our data shed light on the interrelationships among the prototypical heterochromatic features and support a model in which dual recognition by the HP1 chromodomain and the CHAP AT hooks are required for proper heterochromatin formation. PMID- 27681636 TI - Borane-Catalyzed Transfer Hydrogenations of Pyridines with Ammonia Borane. AB - With the use of ammonia borane as a hydrogen source, a borane catalyzed metal free transfer hydrogenation of pyridines was successfully realized for the first time to furnish a variety of piperidines in 44-88% yields with moderate to excellent cis-selectivities. The ease in handling without requiring high pressure H2 makes this transfer hydrogenation practical and useful. PMID- 27681633 TI - Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection. AB - The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 A) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection. PMID- 27681631 TI - C-terminal domain of the RNA chaperone Hfq drives sRNA competition and release of target RNA. AB - The bacterial Sm protein and RNA chaperone Hfq stabilizes small noncoding RNAs (sRNAs) and facilitates their annealing to mRNA targets involved in stress tolerance and virulence. Although an arginine patch on the Sm core is needed for Hfq's RNA chaperone activity, the function of Hfq's intrinsically disordered C terminal domain (CTD) has remained unclear. Here, we use stopped flow spectroscopy to show that the CTD of Escherichia coli Hfq is not needed to accelerate RNA base pairing but is required for the release of dsRNA. The Hfq CTD also mediates competition between sRNAs, offering a kinetic advantage to sRNAs that contact both the proximal and distal faces of the Hfq hexamer. The change in sRNA hierarchy caused by deletion of the Hfq CTD in E. coli alters the sRNA accumulation and the kinetics of sRNA regulation in vivo. We propose that the Hfq CTD displaces sRNAs and annealed sRNA?mRNA complexes from the Sm core, enabling Hfq to chaperone sRNA-mRNA interactions and rapidly cycle between competing targets in the cell. PMID- 27681637 TI - Contact Electrification of Regolith Particles and Chloride Electrolysis: Synthesis of Perchlorates on Mars. AB - Contact electrification of chloride-impregnated martian regolith particles due to eolian agitation and moisture condensation on coalesced oppositely charged grains may lead to spontaneous electrolysis that generates hypochlorite, chlorite, chlorate, and perchlorate with a concomitant reduction of water to hydrogen. This process is not curtailed even if moisture condenses as ice because chloride ionizes on the surface of ice. Limitations dictated by potentials needed for electrolysis and breakdown electric fields enable estimation of the required regolith grain size. The estimated dimension turns out to be of the same order of magnitude as the expected median size of martian regolith, and a simple calculation yields the optimum rate of perchlorate production. Key Words: Mars oxidants-Perchlorate-Dust electrification-Electrolysis. Astrobiology 16, 811-816. PMID- 27681638 TI - MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma. AB - Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients' serum, tumor tissues and OS cell lines. Furthermore, we found that knockdown of miR-24 by its specific inhibitors significantly increased the therapeutic effect of doxorubicin (DOX) on OS cell lines (MG-63 and HOS). Moreover, miR-24 inhibitors resensitized the doxorubicin-resistant MG-63 cells (MG-63/R) and HOS cells (HOS/R) to DOX. As the gene of Bcl-2 interacting mediator of cell death (BIM) was proved to be a target of miR-24 in MG-63/R cells, we further observed that the miR-24 inhibitors promoted the DOX-induced apoptosis via mitochondrial pathway. In addition, results of immunoprecipitation showed the release of second mitochondria derived activator of caspase/ direct IAP binding protein with low pI (Smac/DIABLO) abolished the biological activity of X-linked inhibitor of apoptosis protein (XIAP) by binding with it, which subsequently induced the activation of caspase 9, 7 and 3. In summary, those results strongly suggest that the miR-24-BIM-Smac/DIABLO axis might be a novel target for the treatment of OS. PMID- 27681639 TI - Approach to death in the older emergency department patient. PMID- 27681640 TI - The family health, functioning, social support and child maltreatment risk of families expecting a baby. AB - AIMS AND OBJECTIVES: To describe the family health, functioning, social support and child maltreatment risk and associations between them in families expecting a baby. BACKGROUND: Finland was one of the first countries in banning corporal punishment against children over 30 years ago. Despite of this, studies have shown that parents physically abuse their children. In addition, professionals struggle in intervention of this phenomenon. Abusive parents should be recognised and helped before actual violent behaviour. DESIGN: A follow-up case-control study, with a supportive intervention in the case group (families with a heightened risk) in maternity and child welfare clinics. The baseline results of families are described here. METHODS: Child maltreatment risk in families expecting a baby was measured by Child Abuse Potential Inventory. The health and functioning was measured by Family Health, Functioning and Social Support Scale. Data included 380 families. RESULTS: A total of 78 families had increased risk for child maltreatment. Heightened risk was associated with partners' age, mothers' education, partners' father's mental health problems, mothers' worry about partners' drinking and mothers' difficulties in talking about the family's problems. Risk was associated with family functioning and health. Families with risk received a less support from maternity clinics. Families with child maltreatment risk and related factors were found. CONCLUSIONS: This knowledge can be applied for supporting families both during pregnancy and after the baby is born. Professionals working with families in maternity clinics need tools to recognise families with risk and aid a discussion with them about the family life situation. The Child Abuse Potential, as a part of evaluating the family life situation, seems to prove a useful tool in identifying families at risk. RELEVANCE TO CLINICAL PRACTICE: The results offer a valid and useful tool for recognising families with risk and provide knowledge about high-risk family situations. PMID- 27681642 TI - Foreword to Complementary Medicine in Andrology - special issue Andrologia. PMID- 27681643 TI - Review of local herbal compounds found in the Iranian traditional medicine known to optimise male fertility. AB - The male reproductive function can be influenced by many different factors, including genetic, environmental and socioeconomic parameters leading to a progressive decline. However, the cause of infertility cannot be found in a significant proportion of couples, and even with the presence of the sign of testicular dysfunction or obstructive azoospermia, the main aetiology is not identified. In the absence of knowledge about predisposing factor, targeted therapeutic modalities for male infertility may not be possible, and a wide variety of empiric drug approaches, even with low scientific evidence, have been utilised in current conventional medicine. According to the recently updated reports of the European Association of Urology guidelines on male infertility, the implication of previous recommendations and complementary alternative medicine based on the old literature has been suggested to improve a multifaceted integrative therapeutic approach for this disease. We have reviewed the potential herbal active compounds optimising male fertility, according to the principles of Iranian traditional medicine. PMID- 27681644 TI - An evidence-based approach to medicinal plants for the treatment of sperm abnormalities in traditional Persian medicine. AB - Infertility is defined as inability of a sexually active couple to conceive after 1 year of regular intercourse without contraception. Male factors account for 20% 50% of cases of infertility. The aim of this study was to review medicinal plants that proposed to improve sperm abnormalities in traditional Persian medicine. For this purpose, PubMed, Scopus, GoogleScholar and Cochrane library were explored for medicinal plants used in traditional Persian medicine for sperm abnormalities to obtain studies giving any evidence for their efficacy and pharmacological mechanisms related to male infertility. Data were collected for the years 1966 to March 2015. For some of them, including Chlorophytum borivilianum, Crocus sativus, Nigella sativa, Sesamum indicum, Tribulus terrestris, Mucuna pruriens and Withania somnifera, more reliable evidence was found. The mechanisms involved in the beneficial effects of medicinal plants in sperm abnormalities are antioxidant, anti-inflammatory, anti-oedematous and venotonic activity as well as containing precursors for sperm production and increasing blood testosterone level. Various phytochemical categories including saponins, phytosterols, carotenoids, oxygenated volatile compounds, phenolic compounds and alkaloids seem to be responsible for these beneficial effects. Further studies are recommended for obtaining more conclusive results about the efficacy and safety of the mentioned medicinal plants. PMID- 27681641 TI - The Blueprint of a Minimal Cell: MiniBacillus. AB - Bacillus subtilis is one of the best-studied organisms. Due to the broad knowledge and annotation and the well-developed genetic system, this bacterium is an excellent starting point for genome minimization with the aim of constructing a minimal cell. We have analyzed the genome of B. subtilis and selected all genes that are required to allow life in complex medium at 37 degrees C. This selection is based on the known information on essential genes and functions as well as on gene and protein expression data and gene conservation. The list presented here includes 523 and 119 genes coding for proteins and RNAs, respectively. These proteins and RNAs are required for the basic functions of life in information processing (replication and chromosome maintenance, transcription, translation, protein folding, and secretion), metabolism, cell division, and the integrity of the minimal cell. The completeness of the selected metabolic pathways, reactions, and enzymes was verified by the development of a model of metabolism of the minimal cell. A comparison of the MiniBacillus genome to the recently reported designed minimal genome of Mycoplasma mycoides JCVI-syn3.0 indicates excellent agreement in the information-processing pathways, whereas each species has a metabolism that reflects specific evolution and adaptation. The blueprint of MiniBacillus presented here serves as the starting point for a successive reduction of the B. subtilis genome. PMID- 27681645 TI - A review of the potential of medicinal plants in the management and treatment of male sexual dysfunction. AB - Male sexual dysfunction is a common disorder that appears to be a consequence of a wide range of physical and psychological conditions. Due to mental stress, insufficient physical exercise and various aetiological factors, human being's life is becoming less pleasant, which leads to incapability to have sexual pleasure. The allopathic drugs used for sexual dysfunction are believed to produce a variety of side effects and affect other physiological processes and, ultimately, general health. Therefore, the search for natural supplement from medicinal plants is being intensified probably because of less side effects availability and affordability. Ethnobotanical surveys have indicated a large number of plants traditionally used as aphrodisiacs but only few of them are scientifically validated for the management and treatment of male sexual dysfunction. This article has summarised the medicinal plants traditionally recommended and scientifically validated for the management and treatment of male sexual dysfunction. PMID- 27681646 TI - Indian folklore medicine in managing men's health and wellness. AB - India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders. PMID- 27681647 TI - Effects of aqueous root extract of Carpolobia alba G. Don on sexual behaviour in adult male rats. AB - Several lines say that a number of natural products, mostly plant based, have been claimed to cure male sexual dysfunction. One of such botanicals is Carpolobia alba G. Don which is used in Cameroon to treat erectile dysfunction and related male sexual debilities. However, the traditional claim has not been scientifically tested. Thirty adult male rats (five groups of six animals) were orally treated daily with distilled water, sildenafil citrate (positive control), 75, 150, 300 mg/kg of C. alba G. Don roots aqueous extract. The erection and ejaculation properties were recorded on the first, seventh and fourteenth day of treatment by following copulation settings: number of erections (NE), mount frequency (MF), intromission frequency (IF), ejaculation frequency (EF), mount latency (ML), intromission latency (IL), ejaculation latency (EL), average interval of copulation (AIC) and post-ejaculatory interval (PEI). The extract resulted in an improvement of copulation parameters through significant reduction (p < .001) of PEI, ML and IL and significant increase (p < .001) in the NE, MF, IF, EF, EL and AIC. These results indicate a pro-erectile and pro-ejaculatory potential of aqueous root extract of this plant in male rats. PMID- 27681648 TI - Effect of butanolic fraction of yellow and black maca (Lepidium meyenii) on the sperm count of adult mice. AB - Lepidium meyenii, known as maca, is a popular nutraceutical food which is grown over 4,000 m above sea level in the Peruvian central highlands. Maca contains alkaloids, but there are no studies on their biological effects. The butanol fraction obtained from methanol extract of maca hypocotyls contains alkaloids. The effects of butanol/aqueous fractions partitioned from methanol extract of yellow and black maca were examined. Total phenolic content (TPC) and antioxidant capacity by 2,2'-diphenyl-1-picrylhydrazyl were used to evaluate maca fractions in vitro. Daily sperm production and sperm count in epididymis and vas deferens in mice were determined as biological effect of maca extracts in vivo. Yellow maca (21.7%+/-0.69) had better antioxidant capacity than black maca (18.2% +/- 0.12; p < .01). Antioxidant activity was better in the methanolic fraction than in the aqueous fraction of yellow or black maca. TPC is higher in the aqueous fraction than in the methanolic extract of yellow or black maca. Black maca administration resulted in higher concentration of sperm count in epididymis and vas deferens compared to yellow maca. A higher biological effect was observed in methanolic extract and in aqueous extract than in the butanol fraction of maca. In conclusion, better biological effect was observed in the methanolic extract of maca than in its partitioned fractions. PMID- 27681650 TI - Effect of Lepidium meyenii (maca) on testicular function of mice with chemically and physically induced subfertility. AB - The aim of this study was to evaluate the effect of Lepidium meyenii (maca) in chemically and physically subfertile mice. After 35 days, the following groups of mice were evaluated: control, sham, chemical subfertility, chemical subfertility maca-supplemented, physical subfertility, physical subfertility-maca-supplemented and maca-supplemented only. Motility (32.36% +/- 5.34%) and sperm count (44.4 +/- 5.37 * 10(6) /ml) in the chemically and physically subfertile mice (11.81% +/- 4.06%, 17.34 +/- 13.07 * 10(6) /ml) decreased compared to the control (75.53% +/- 2.97% and 57.4 +/- 19.6 10(6) /ml) and sham (53.5% +/- 7.86% and 58.4 +/- 14.10 10(6) /ml). Maca was able to reverse the deleterious effect of motility (76.36 +/ 1.97) as well as sperm count (53.5 +/- 9.18 * 10(6) /ml) on chemical subfertility. In contrast, maca did not reverse the effects of induced physical subfertility nor motility (18.78% +/- 14.41%) or sperm count (20.17 +/- 11.20 * 10(6) /ml). The percentage of sperm DNA fragmentation in the physically subfertile mice increased (11.1% +/- 19.29%) compared to the control (0.84% +/- 0.85%). However, in the physically subfertile group, maca decreased sperm DNA fragmentation (2.29% +/- 2.30%) closer to the sham (1.04% +/- 0.62%) and the control (0.84% +/- 0.85%). The group supplemented only with maca showed 0.54% +/- 0.50% of spermatozoa with DNA fragmentation. Yet, the differences observed were statistically not significant. In conclusion, it appears that maca activates the cytochrome P450 system after chemically induced subfertility. However, it does not reverse the low mitochondrial membrane potential in spermatozoa compromised in the physical subfertility group. PMID- 27681649 TI - Red Maca (Lepidium meyenii) did not affect cell viability despite increased androgen receptor and prostate-specific antigen gene expression in the human prostate cancer cell line LNCaP. AB - We examined whether aqueous extract of Lepidium meyenii (red Maca) could inhibit growth, potentiate apoptotic activity of two anticancer drugs Taxol and 2 methoxyestradiol (2ME) or change mRNA expression for the androgen target genes, androgen receptor (Ar) and prostate-specific antigen (Psa) in the human prostate cancer cell line LNCaP. Red Maca aqueous extract at 0, 10, 20, 40 or 80 MUg/ml was added to LNCaP cells, and viability was evaluated by the MTS assay at 24 or 48 hr after treatment. Furthermore, LNCaP cells were treated with 80 MUg/ml of red Maca plus Taxol or 2ME 5 MUM and viability was assessed 48 hr later. Finally, LNCaP cells were treated with red Maca 0, 20, 40 or 80 MUg/ml, and 12 hr later, mRNA level for Ar or Psa was assessed by real-time PCR. Treatment with red Maca did not affect viability of LNCaP cells. Apoptotic activity induced by Taxol and 2ME in LNCaP cells was not altered with red Maca treatment. Relative expression of the mRNA for Ar and Psa increased with red Maca 20 and 40 MUg/ml, but not at 80 MUg/ml. We conclude that red Maca aqueous extract does not have toxic effects, but stimulates androgen signalling in LNCaP cells. PMID- 27681652 TI - Psychiatric comorbidities in children and adolescents with psoriasis: a population-based cohort study. PMID- 27681651 TI - Adalimumab for the treatment of actinic granuloma. PMID- 27681654 TI - Dynamic left ventricular changes in patients with gestational diabetes: A speckle tracking echocardiography study. AB - PURPOSE: The left ventricle (LV) undergoes physiologic remodeling in adaptation to the hemodynamic changes that occur in pregnancy. Speckle tracking echocardiography (STE) is a novel and reliable tool to evaluate subtle myocardial alterations that have been utilized to assess myocardial changes in patients with diabetes mellitus (DM) but not in patients with gestational DM (GDM). We seek to evaluate changes in LV function using STE in patients with GDM compared with women with normal pregnancy. METHODS: This was a single-center retrospective cohort study. A total of 312 pregnant patients that underwent transthoracic echocardiogram (TTE) between 2009 and 2014 were screened. After excluding patients with comorbidities or insufficient data, 90 women were included. TTE from the second and third trimester for each patient were then reviewed, and STE analysis was performed. RESULTS: Of the 90 subjects, 72 had normal pregnancies and 18 developed GDM. There was no difference in LV end-diastolic diameter (4.73 +/- 0.40 versus 4.60 +/- 0.56, p = 0.25), LV end-systolic diameter (3.12 +/- 0.35 versus 2.91 +/- 0.61, p = 0.152), or ejection fraction (62.26 +/- 4.12 versus 63.50 +/- 5.24, p = 0.314) between the two groups. Global longitudinal strain was lower (-19.8 +/- 3.34 versus -17.2 +/- 2.18, p < 0.001) in patients with GDM, while time-to-peak strain was greater (0.43 +/- 0.05 versus 0.50 +/- 0.06, p < 0.001). Circumferential and radial strains were preserved in both groups. CONCLUSIONS: Although conventional TTE variables show preserved LV size and function, LV longitudinal strain suggests subclinical myocardial dysfunction in patients with GDM. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:20-27, 2017. PMID- 27681653 TI - Interrelationship between family history of alcoholism and generational status in the prediction of alcohol dependence in US Hispanics. AB - BACKGROUND: Both a family history of alcoholism and migration-related factors like US v. foreign nativity increase the risk for developing alcohol use disorders in Hispanic Americans. For this study, we integrated these two lines of research to test whether the relationship between familial alcoholism and alcohol dependence changes with successive generations in the United States. METHOD: Data were from the waves 1 and 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Subjects self-identified Hispanic ethnicity (N = 4122; n = 1784 first, n = 1169 second, and n = 1169 third or later generation) and reported ever consuming ?12 drinks in a 1-year period. A family history of alcoholism was assessed in first- and second-degree relatives. Analyses predicting the number of alcohol dependence symptoms were path models. RESULTS: Alcohol dependence symptoms were associated with a stronger family history of alcoholism and later generational status. There was a significant interaction effect between familial alcoholism and generational status; the relationship of familial alcoholism with alcohol dependence symptoms increased significantly with successive generations in the United States, more strongly in women than men. Acculturation partially mediated the interaction effect between familial alcoholism and generational status on alcohol dependence, although not in the expected direction. CONCLUSIONS: Familial alcoholism interacted with generational status in predicting alcohol dependence symptoms in US Hispanic drinkers. This relationship suggests that heritability for alcoholism is influenced by a higher-order environmental factor, likely characterized by a relaxing of social restrictions on drinking. PMID- 27681656 TI - Reduced fetal brain fissures depth in fetuses with congenital heart diseases. AB - OBJECTIVE: To screen and detect cortex gyration in fetuses with congenital heart disease (CHD) using Ultrasonography (US) during routine obstetric scans. METHODS: The depth of the Sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine (CF) fissure were prospectively serially measured and compared in 45 fetuses with CHD and 45 normal fetuses. Cardiac hemodynamic parameters, including aortic valve diameter (AV), pulmonary valve diameter (PV), velocity time integral of the aortic valve (VTIav), and velocity time integral of the pulmonary valve (VTIpv), were recorded. Correlations between the fissure depths and the prenatal cardiac hemodynamic parameters and postnatal neurodevelopmental scores were assessed. RESULTS: SF, POF, and CF were decreased in CHD fetuses compared with the controls in late of pregnancy (P < 0.01). The diagnostic category was independently associated with smaller fissure depths in fetuses with CHD (adjusted R2 = 0.472 for SF, 0.465 for POF, and 0.425 for CF). Correlations were observed between small fissure depths and decreased left heart hemodynamic parameters (AV and VTIav) in fetuses with CHD. The SF depth was positively correlated with the neurodevelopmental scores (P < 0.01). CONCLUSIONS: US can be used to screen for abnormal fetal brain cortex development during routine obstetric scans and to evaluate the maturation progress during close follow-up. (c) 2016 John Wiley & Sons, Ltd. PMID- 27681655 TI - Marine Habitat Selection by Marbled Murrelets (Brachyramphus marmoratus) during the Breeding Season. AB - The marbled murrelet (Brachyramphus marmoratus) is a declining seabird that is well-known for nesting in coastal old-growth forests in the Pacific Northwest. Most studies of habitat selection have focused on modeling terrestrial nesting habitat even though marine habitat is believed to be a major contributor to population declines in some regions. To address this information gap, we conducted a 5-year study of marine resource selection by murrelets in Washington, which contains a population experiencing the steepest documented declines and where marine habitat is believed to be compromised. Across five years we tracked 157 radio-tagged murrelets during the breeding season (May to August), and used discrete choice models to examine habitat selection. Using an information theoretic approach, our global model had the most support, suggesting that murrelet resource selection at-sea is affected by many factors, both terrestrial and marine. Locations with higher amounts of nesting habitat (beta = 21.49, P < 0.001) that were closer to shore (beta = -0.0007, P < 0.001) and in cool waters (beta = -0.2026, P < 0.001) with low footprint (beta = -0.0087, P < 0.001) had higher probabilities of use. While past conservation efforts have focused on protecting terrestrial nesting habitat, we echo many past studies calling for future efforts to protect marine habitat for murrelets, as the current emphasis on terrestrial habitat alone may be insufficient for conserving populations. In particular, marine areas in close proximity to old-growth nesting habitat appear important for murrelets during the breeding season and should be priorities for protection. PMID- 27681657 TI - Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn's disease. AB - BACKGROUND: The prevention of relapse is a major issue in the management of Crohn's disease. Corticosteroids, the mainstay of treatment of acute exacerbations, are not effective for maintenance of remission and its chronic use is limited by numerous adverse events. Randomised controlled trials assessing the efficacy of oral 5-aminosalicylic acid (5-ASA) agents for maintenance of medically-induced remission in Crohn's disease have produced conflicting results. OBJECTIVES: To conduct a systematic review to evaluate the efficacy and safety of oral 5-ASA agents for the maintenance of medically-induced remission in Crohn's disease. SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL and the IBD Group Specialized Register from inception to 8 June 2016. We also searched reference lists and conference proceedings. SELECTION CRITERIA: We included randomised controlled trials that compared oral 5-ASA agents to either placebo or sulphasalazine in patients with quiescent Crohn's disease. The trials had to have a treatment duration of at least six months. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and performed the risk of bias assessment. Any disagreements were resolved by discussion and consensus. The primary outcome measure was the occurrence of relapse as defined by the primary studies. Secondary outcomes included time to relapse, adverse events, withdrawal due to adverse events and serious adverse events. We calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (95% CI) using a fixed-effect model. All data were analysed on an intention-to-treat basis and drop-outs were considered to be relapses. Sensitivity analyses included an available case analysis where drop-outs were ignored and using a random-effects model. We evaluated the overall quality of the evidence supporting the outcomes using the GRADE criteria. MAIN RESULTS: Twelve studies (2146 participants) that compared 5 ASA to placebo were included. We did not identify any studies that compared sulphasalazine to placebo. Seven studies were judged to be at low risk of bias. The other studies were judged to have an unclear risk of bias for various items due to insufficient details to allow for a judgement. There was no statistically significant difference in relapse rates at 12 months. Fifty-three per cent (526/998) of 5-ASA patients (dose 1.6 g to 4 g/day) relapsed at 12 months compared to 54% (544/1016) of placebo patients (RR 0.98, 95% CI 0.91 to 1.07; 11 studies; 2014 patients; moderate-quality evidence). Sensitivity analyses based on an available case analysis and a random-effects model had no impact on the results. One study found no difference in relapse rates at 24 months. Fifty-four per cent (31/57) of 5-ASA patients (dose 2 g/day) relapsed at 24 months compared to 58% (36/62) of placebo patients (RR 0.94, 95% CI 0.68 to 1.29, 119 patients; low-quality evidence). One paediatric study found no statistically significant difference in relapse rates at 12 months. Sixty-two per cent (29/47) of paediatric 5-ASA patients (dose 50 mg/kg/day) relapsed at 12 months compared to 64% (35/55) of paediatric placebo patients (RR 0.97, 95% CI 0.72 to 1.31; 102 patients; moderate-quality evidence). There was no statistically significant difference in the proportion of patients who experienced an adverse event, withdrawal due to adverse events or serious adverse events. Thirty-four per cent (307/900) of 5-ASA patients had at least one adverse event compared to 33% (301/914) of placebo patients (RR 1.05, 95% CI 0.95 to 1.17; 10 studies; 1814 patients). Fourteen per cent (127/917) of 5-ASA patients withdrew due to adverse events compared to 13% (119/916) of placebo patients (RR 1.11, 95% CI 0.88 to 1.38; 9 studies; 1833 patients). One per cent (3/293) of 5-ASA patients had a serious adverse event compared to 0.7% (2/283) of placebo patients (RR 1.43, 95% CI 0.24 to 2.83; 3 studies; 576 patients). Common adverse events reported in the studies included diarrhoea, nausea and vomiting, abdominal pain, headache and skin rash. AUTHORS' CONCLUSIONS: We found no evidence in this review to suggest that oral 5-ASA preparations are superior to placebo for the maintenance of medically-induced remission in patients with Crohn's disease. Additional randomised trials may not be justified. PMID- 27681658 TI - Challenges encountered in the conduct of Optimal Health: A patient-centered comparative effectiveness study of interventions for adults with serious mental illness. AB - BACKGROUND: The aim of patient-centered comparative effectiveness research is to conduct stakeholder-driven investigations that identify which interventions are most effective for which patients under specific circumstances. Conducting this research in real-world settings comes with unique experiences and challenges. We provide the study design, challenges confronted, and the solutions we devised for Optimal Health, a stakeholder-informed patient-centered comparative effectiveness study focused on the needs of seriously mentally ill individuals receiving case management services in community mental health centers across Pennsylvania. METHODS: Optimal Health, supported by the Patient-Centered Outcomes Research Institute, is a cluster-randomized trial of two evidence-based interventions for improving health and wellness across 11 provider sites. Participants were followed for 18-24 months, with repeated measurements of self-reported health status and activation in care and administrative measurements of primary and specialty health service utilization. Health-related quality of life, engagement in care, and service utilization are to be compared via random effects mixed models. Stakeholders were, and continue to be, engaged via focus groups, interviews, and stakeholder advisory board meetings. A learning collaborative model was used to support shared learning and implementation fidelity across provider sites. RESULTS: From 1 November 2013 through 15 July 2014, we recruited 1229 adults with serious mental illness, representing 85.1% of those eligible for study participation. Of these, 713 are in the Provider-Supported arm of the study and 516 in Patient Self-Directed Care. Across five data collection time points, we retained 86% and 83% of the participants in the Provider-Supported and Self Directed arms, respectively. LESSONS LEARNED: Lessons learned relate to estimation of the size of our study population, the value of multiple data sources, and intervention training and implementation. The use of historical claims data can lead to an overestimation of eligible participants and, subsequently, a reduced study sample and an imbalance between intervention arms. Disruptions in continuity of care in real-world settings can pose challenges to on-site self-report data collection, although the inclusion of multiple data sources in study design can improve data completeness. Geographic dispersion of rural provider sites and staff turnover can lead to training and intervention fidelity challenges that can be overcome with the use of a "train-the-trainer" model, "wellness champions," and the use of a Learning Collaborative approach. Stakeholder engagement in mitigating these challenges proved to be critical to study progress. CONCLUSION: Conducting real-world patient-centered comparative effectiveness research in healthcare systems that care for seriously mentally ill persons is an important yet challenging undertaking, one which requires flexibility in identifying potential adaptations within all major study phases. Advice from a wide range of stakeholders is critical in development of successful strategies. PMID- 27681659 TI - A system for the treatment of nocturnal enuresis in children. AB - BACKGROUND: This paper presents our findings related to the treatment of children with nocturnal enuresis using our own rehabilitation system. The basic three elements of the therapeutic process include: 1st stage: assessment of the way in which a child urinates; 2nd stage: treatment of bladder dysfunctions; 3rd stage: learning to wake up in order to urinate. METHODS: Medical records of 198 children were used in the study. Group 1: children with monosymptomatic nocturnal enuresis. Group 2: children with polisymptomatic nocturnal enuresis. Group 1 was treated with the use of alarm device (AD). The treatment in group 2 started with the urotherapy and pharamacotherapy of bladder dysfunctions, if the treatment was effective a therapy with the use of alarm device was recommended. RESULTS: A therapy with an AD was carried out in 122 children, 6 started to wake up without episodes of NE that would trigger the alarm, in 31 the ability to wake up in order to urinate developed in the first month of the therapy, 35 were cured after 2 months, in another 5 children the therapy was continued and was successfully completed in the 3rd month of using the AD. In total, 77 children (63.1%) treated using AD were considered as cured. CONCLUSIONS: The system for the treatment based on the functional division is effective both in children with normal bladder function and in patients with symptoms of urinary tract dysfunction. The treatment with AD is more effective in children with monosymptomatic than with polisymptomatic nocturnal enuresis. PMID- 27681660 TI - Health related quality of life after radical cystectomy in women: orthotopic neobladder versus ileal loop conduit and impact of incontinence. AB - BACKGROUND: Enough data about health related quality of life (HRQOL) after radical cystectomy (RC) and urinary diversion (UD) in women is still lacking. The objectives are to evaluate HRQOL in women after RC and orthotopic neobladder (ONB) versus ileal loop conduit (IC) and to assess the impact of urinary continence. METHODS: The study included 145 women who underwent RC and came for routine follow-up. HRQOL was assessed by two questionnaires (EORTC-QLQ-C30and FACT-Bl). ONB group was stratified to: totally continent, with nocturnal incontinence (NI) and patients in chronic urinary retention (CUR) and maintained on CIC. The orthotopic group (as a whole and its 3 subgroups) was compared to IC. RESULTS: ONB group included 22 continent women, 35 with NI and 27 in CUR and on CIC. There were no statistically significant differences between ONB and IC groups in all domains of the two questionnaires. However, continent women showed statistically significant better most of EORTC-QLQ-C30 scales and emotional well being, functional well-being, bladder cancer subscale and FACT-Bl total Score (P?0.05) than IC group. Similarly, women in CUR showed statistically significant better global health and physical functioning EORTC-QLQ-C30 scores (P values=0.0001, 0.01) and all domains of FACT-Bl. On the other hand, women with NI showed statistically significant lower values in all domains of the EORTC-QLQ-C30 and FACT-Bl than IC group. CONCLUSIONS: In women, HRQOL is better after ONB than IC as long as continence status is preserved. If incontinence is expected, IC may be a better option for UD. PMID- 27681662 TI - Postoperative cystographic findings as an independent predictor of urinary incontinence three months after radical prostatectomy. AB - BACKGROUND: Postoperative cystogram has been used to identify clinically significant leaks before catheter removal after radical prostatectomy (RP). The aim of the present study was to investigate the relationship between cystogram findings after RP and early urinary incontinence. METHODS: From January 2011 to February 2015, 417 patients who had undergone a cystography after RP at our hospital were retrospectively analyzed. The ratio dividing the length from the upper part of the pubic symphysis to the neck of the bladder with the length of the total pubic symphysis height (bladder neck pubic symphysis ratio [BNPSR]) was measured and urinary incontinence was assessed by the subjects' use of a pad. RESULTS: In the total patient sample, urinary incontinence 3 months after RP was 28.5%. The mean BNPSR for the group with urinary incontinence and the group without was 0.49+/-0.26 and 0.38+/-0.17, respectively (P<0.001). Additionally, the rate of urine leakage in the group with urinary incontinence and the group without was observed to be 14.3% and 6.4% on cystogram, respectively (P=0.012). Open vs. robotic surgeries resulted in urinary incontinence frequencies of 41.0% vs. 22.3% (P<0.001). In a multivariate logistic regression analysis, both a high BNPS ratio (Odds ratio [OR], 23.14; P<0.001) and surgical technique (OR=2.29; P<0.001) were shown to be independent predictive factors for urinary incontinence 3 months after surgery. CONCLUSIONS: BNPSR measured by cystogram after RP can be useful for predicting the occurrence of urinary incontinence and managing a patient's progress after RP. PMID- 27681663 TI - A prospective evaluation of the availability and utility of the Ambulance Call Record in the emergency department - ERRATUM. PMID- 27681664 TI - Mechanism of Conductivity Relaxation in Liquid and Polymeric Electrolytes: Direct Link between Conductivity and Diffusivity. AB - Combining broadband impedance spectroscopy, differential scanning calorimetry, and nuclear magnetic resonance we analyzed charge and mass transport in two polymerized ionic liquids and one of their monomeric precursors. In order to establish a general procedure for extracting single-particle diffusivity from their conductivity spectra, we critically assessed several approaches previously employed to describe the onset of diffusive charge dynamics and of the electrode polarization in ion conducting materials. Based on the analysis of the permittivity spectra, we demonstrate that the conductivity relaxation process provides information on ion diffusion and the magnitude of cross-correlation effects between ionic motions. A new approach is introduced which is able to estimate ionic diffusivities from the characteristic times of conductivity relaxation and ion concentration without any adjustable parameters. This opens the venue for a deeper understanding of charge transport in concentrated and diluted electrolyte solutions. PMID- 27681665 TI - Flow Injection Single Particle Inductively Coupled Plasma Mass Spectrometry: An Original Simple Approach for the Characterization of Metal-Based Nanoparticles. AB - In recent years, single-particle inductively coupled plasma mass spectrometry (spICPMS) has emerged as a reliable tool that can both count metal-containing nanoparticles and measure their mass, thereby allowing sizing if their shape, density, and composition are known. However, the methodology associated with the current spICPMS approach for mass determination requires determination of both the sample uptake rate and the sample introduction efficiency of the nebulization system. In this paper, the proof of concept of a novel approach based on flow injection (FI) analysis coupled to ICPMS, i.e., FI-spICPMS, is presented. Unlike the established technique, this method does not require a determination of the transport efficiency and of the sample uptake rate for the accurate measurement of particle mass. It also only requires a measurement of the transport efficiency for determination of the particle number. Unlike the traditional spICPMS approach, the measurement of transport efficiency by FI-spICPMS is not affected by changes in sample uptake rate. The efficiency of FI-spICPMS is demonstrated through accurate determination of the particle number and size of 60 nm citrate coated gold nanoparticles suspended in high-purity water. Despite being simpler, the method provides similar results to those obtained by the established spICPMS method. With a 5 ms dwell time and 200 MUs settling time, the size detection limit is 20 nm, i.e., the same as with spICPMS. PMID- 27681666 TI - Effect of Al2O3 Deposition on Performance of Top-Gated Monolayer MoS2-Based Field Effect Transistor. AB - Deposition of high-k dielectrics on two-dimensional MoS2 is an important process for successful application of the transition-metal dichalcogenides in electronic devices. Here, we show the effect of H2O reactant exposure on monolayer (1L) MoS2 during atomic layer deposition (ALD) of Al2O3. The results showed that the ALD Al2O3 caused degradation of the performance of 1L MoS2 field effect transistors (FETs) owing to the formation of Mo-O bonding and trapping of H2O molecules at the Al2O3/MoS2 interface. Furthermore, we demonstrated that reduced duration of exposure to H2O reactant and postdeposition annealing were essential to the enhancement of the performance of top-gated 1L MoS2 FETs. The mobility and on/off current ratios were increased by factors of approximately 40 and 103, respectively, with reduced duration of exposure to H2O reactant and with postdeposition annealing. PMID- 27681667 TI - Nonequilibrium Hybridization Enables Discrimination of a Point Mutation within 5 40 degrees C. AB - Detection of point mutations and single nucleotide polymorphisms in DNA and RNA has a growing importance in biology, biotechnology, and medicine. For the application at hand, hybridization assays are often used. Traditionally, they differentiate point mutations only at elevated temperatures (>40 degrees C) and in narrow intervals (DeltaT = 1-10 degrees C). The current study demonstrates that a specially designed multistranded DNA probe can differentiate point mutations in the range of 5-40 degrees C. This unprecedentedly broad ambient temperature range is enabled by a controlled combination of (i) nonequilibrium hybridization conditions and (ii) a mismatch-induced increase of equilibration time in respect to that of a fully matched complex, which we dub "kinetic inversion". PMID- 27681668 TI - The Effect of a Perinatal Breastfeeding Support Program on Breastfeeding Outcomes in Primiparous Mothers. AB - The purpose of this study was to examine the effect of a self-efficacy intervention on primiparous mothers' breastfeeding behaviors. Participants were recruited from an antenatal clinic at a university-affiliated hospital. Seventy five primiparous mothers were recruited from November 2013 to February 2014 for the control group, and 75 primiparous mothers were recruited from March to June 2014 for the intervention group. The intervention group participated in a 1-hr prenatal breastfeeding workshop and a 1-hr breastfeeding counseling session within 24 hr after delivery. The Breastfeeding Self-Efficacy Scale-Short Form and the infant feeding method were assessed at hospital discharge, as well as 4 and 8 weeks postpartum. The breastfeeding support program was found to be effective and beneficial to mothers. Nurses should incorporate breastfeeding self-efficacy interventions into their routine care to support new mothers and to increase their breastfeeding self-efficacy and the duration of their breastfeeding exclusivity. PMID- 27681669 TI - Polycystic Ovarian Syndrome - Issue 30.8. PMID- 27681671 TI - Synthesis of a Fluorescent Acridone using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence. AB - A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the acridone product of the synthesis are analyzed by common techniques available in most undergraduate chemistry laboratories, such as melting point, TLC, IR spectroscopy, UV-Vis spectroscopy, and fluorescence spectroscopy. Yields for each transformation in the synthesis are generally moderately low to good (20-90%) and nearly all of the students (>90%) who attempted the synthesis were able to produce the final acridone product. PMID- 27681673 TI - National Survey of Hospital Nursing Research, Part 2: Facilitators and Hindrances. PMID- 27681672 TI - Magnet(r) Culture and Leadership: Research and Empirical Outcomes. PMID- 27681670 TI - Nutrient sensing, signal transduction and immune responses. AB - Most cells in the body have a constant supply of nutrients, which are required to sustain cellular metabolism and functions. In contrast, cells of the immune system can encounter conditions with a limited nutrient supply during the course of an immune response. Cells of the immune system frequently operate in complex nutrient restricted microenvironments such as tumour or inflammatory sites. The concentrations of key nutrients such as glucose and certain amino acids, can be low at these sites, and this can have an impact upon immune cell function. Nutrient sufficiency is important to supply the metabolic and biosynthetic pathways of immune cells. In addition nutrients can also act as important cues that influence immunological signalling pathways to affect the function of immune cells. This review will describe the various nutrient sensing signalling pathways and discuss the evidence that nutrients are critical signals that shape immune responses. PMID- 27681674 TI - Nursing Research Fellowship: Building Nursing Research Infrastructure in a Hospital. PMID- 27681676 TI - Promoting Evidence-Based Practice Through a Research Training Program for Point of-Care Clinicians. PMID- 27681675 TI - Creative Approaches to Increasing Hospital-Based Nursing Research. PMID- 27681677 TI - Supporting Research Takes Leadership Commitment. PMID- 27681678 TI - Nurses' Research Capacity, Use of Evidence, and Research Productivity in Acute Care: Year 1 Findings From a Partnership Study. PMID- 27681679 TI - Fostering Clinical Nurse Research in a Hospital Context. PMID- 27681680 TI - Transforming Practice Through Publication: A Community Hospital Approach to the Creation of a Research-Intensive Environment. PMID- 27681681 TI - Creating Staff Confidence in Distinguishing Between Performance Improvement and Research Studies: A User-Friendly Worksheet. PMID- 27681682 TI - National Survey of Hospital Nursing Research, Part 1: Research Requirements and Outcomes. PMID- 27681684 TI - The Impairing Effect of Mental Fatigue on Visual Sustained Attention under Monotonous Multi-Object Visual Attention Task in Long Durations: An Event-Related Potential Based Study. AB - The impairing effects of mental fatigue on visual sustained attention were assessed by event-related potentials (ERPs). Subjects performed a dual visual task, which includes a continuous tracking task (primary task) and a random signal detection task (secondary task), for 63 minutes nonstop in order to elicit ERPs. In this period, the data such as subjective levels of mental fatigue, behavioral performance measures, and electroencephalograms were recorded for each subject. Comparing data from the first interval (0-25 min) to that of the second, the following phenomena were observed: the subjective fatigue ratings increased with time, which indicates that performing the tasks leads to increase in mental fatigue levels; reaction times prolonged and accuracy rates decreased in the second interval, which indicates that subjects' sustained attention decreased.; In the ERP data, the P3 amplitudes elicited by the random signals decreased, while the P3 latencies increased in the second interval. These results suggest that mental fatigue can modulate the higher-level cognitive processes, in terms of less attentional resources allocated to the random stimuli, which leads to decreased speed in information evaluating and decision making against the stimuli. These findings provide new insights into the question that how mental fatigue affects visual sustained attention and, therefore, can help to design countermeasures to prevent accidents caused by low visual sustained attention. PMID- 27681683 TI - Distribution of Human Norovirus in the Coastal Waters of South Korea. AB - The presence of human norovirus in the aquatic environment can cause outbreaks related to recreational activities and the consumption of norovirus-contaminated clams. In this study, we investigated the prevalence of norovirus genogroups I (GI) and II (GII) in the coastal aquatic environment in South Korea (March 2014 to February 2015). A total of 504 water samples were collected periodically from four coastal areas (total sites = 63), of which 44 sites were in estuaries (clam fisheries) and 19 were in inflow streams. RT-PCR analysis targeting ORF2 region C revealed that 20.6% of the water samples were contaminated by GI (13.3%) or GII (16.6%). The prevalence of human norovirus was higher in winter/spring than in summer/fall, and higher in inflow streams (50.0%) than in estuaries (7.9%). A total of 229 human norovirus sequences were identified from the water samples, and phylogenetic analysis showed that the sequences clustered into eight GI genotypes (GI.1, 2, 3, 4, 5, 6, 7, and 9) and nine GII genotypes (GII.2, 3, 4, 5, 6, 11, 13, 17, and 21). This study highlighted three issues: 1) a strong correlation between norovirus contamination via inflow streams and coastal areas used in clam fisheries; 2) increased prevalence of certain non-GII.4 genotypes, exceeding that of the GII.4 pandemic variants; 3) seasonal shifts in the dominant genotypes of both GI and GII. PMID- 27681685 TI - Desperately seeking consistency: Student nurses' experiences and expectations of academic supervision. AB - BACKGROUND: Academic supervision - the support available to students when writing assignments - is a fundamental element in the provision of support within nurse education. Not only can it underpin high levels of academic achievement, but it also has a role in enhancing the retention of students. Despite its importance, there is little investigation of undergraduate academic supervision within the nursing literature. OBJECTIVES: To explore students' experiences and expectations of academic supervision as part of an undergraduate programme of nurse education. DESIGN: A qualitative approach to explore student perceptions. SETTING: The research was undertaken at a Higher Education Institution in the United Kingdom. The institution offers undergraduate nurse education programmes to approximately 800 students. PARTICIPANTS: Eight pre-registration nursing students from a Bachelor of Science programme participated in a focus group interview. All were in the first semester of their final year. METHODS: Data were collected using focus group interviewing, based around a semistructured question framework. The focus groups explored students' expectations and previous experiences of academic supervision. The focus group was recorded, responses were transcribed and thematic analysis was undertaken to identify key findings. RESULTS: Three themes were identified from the data: relationship with supervisor, variation between supervisors, and the link between supervision and marking. Overall, students identified frustration with variability in the provision of academic supervision. CONCLUSIONS: Effective academic supervision depends on a strong relationship between student and supervisor - something that can be difficult to achieve if supervision is only for a short period of time. Equally, students crave a consistent approach to supervision, in terms of both the amount and content of feedback. Students are able to identify and articulate a clear link between effective supervision and academic achievement. PMID- 27681686 TI - Molecular features of bile salt hydrolases and relevance in human health. AB - BACKGROUND: Bile salt hydrolase (BSH) enzyme is responsible for the de conjugation of bile salts by commensal bacteria, thus playing a vital role in their colonization and survival in the mammalian intestine and determination of their probiotic potential. Further, bile deconjugation also leads to lowering of cholesterol and alterations in energy homeostasis, thus making BSH a clinically important enzyme. SCOPE OF THE REVIEW: Many recent observations have indicated that BSH may be involved in a multifaceted array of roles, directly or indirectly in the host and microbial physiology. BSH paralogues have now been found to occur in different microbes including free-living and pathogenic bacteria and Archaea. BSHs from various sources also show differential activity and substrate spectrum. Certain bacteria are known to possess multiple genes for BSH enzymes. BSHs have been reported to influence different metabolic phenomena, including bacterial pathogenesis and the maintenance of lipid and glucose homeostasis in the host. These observations necessitate an intense study into the biochemical, structural and regulatory features of BSH enzymes to better understand their role in regulating bacterial and host metabolism. MAJOR CONCLUSIONS: In this review, the available information on the characteristics of BSH enzymes have been organized in order to understand their interactions with a wide range of substrates and their myriad physiological roles, from bile resistance to signalling mechanisms. GENERAL SIGNIFICANCE: A detailed exploration of BSH architecture and regulation could provide insights into its evolution and a deeper appreciation of the multiple functions of this enzyme relevant to healthcare. PMID- 27681687 TI - Random Item Generation Is Affected by Age. AB - Purpose: Random item generation (RIG) involves central executive functioning. Measuring aspects of random sequences can therefore provide a simple method to complement other tools for cognitive assessment. We examine the extent to which RIG relates to specific measures of cognitive function, and whether those measures can be estimated using RIG only. Method: Twelve healthy older adults (age: M = 70.3 years, SD = 4.9; 8 women and 4 men) and 20 healthy young adults (age: M = 24 years, SD = 4.0; 12 women and 8 men) participated in this pilot study. Each completed a RIG task, along with the color Stroop test, the Repeatable Battery for the Assessment of Neuropsychological Status, and the Peabody Picture Vocabulary Test-Fourth Edition (Dunn & Dunn, 2007). Several statistical features extracted from RIG sequences, including recurrence quantification, were found to be related to the other measures through correlation, regression, and a neural-network model. Results: The authors found significant effects of age in RIG and demonstrate that nonlinear machine learning can use measures of RIG to accurately predict outcomes from other tools. Conclusions: These results suggest that RIG can be used as a relatively simple predictor for other tools and in particular seems promising as a potential screening tool for selective attention in healthy aging. PMID- 27681688 TI - Dysregulation of calcium channels decreases parasecretion in pancreatic beta cells in rats born small for gestational age. AB - OBJECTIVE: To investigate the role of intrauterine malnourishment in the development and function of pancreatic islet beta-cells. METHODS: Whole-cell patch clamping was used to record voltage-gated calcium channel (VGCC)-mediated currents. Insulin secretion was detected by measuring capacitance using a sequence of sine wave stimuli. VGCC currents and insulin secretion were measured in the small for gestational age (SGA) group treated with human recombinant growth hormone (hGH). RESULTS: The membrane capacitance in the SGA group (6.4 +/- 0.9 fF/Pf) was significantly reduced. Calcium current density and peak current density in the SGA group were also markedly decreased, whereas other measurements of calcium channels were unaltered. Treatment with hGH significantly rescued the membrane capacitance, whereas calcium channels were not affected. CONCLUSION: Our data suggest that decreased beta-cell secretion is caused by a decreased expression of calcium channels and reduced calcium currents. hGH restores beta cell secretion in SGA animals, possibly independently of VGCC. PMID- 27681690 TI - Breast Cancer Posttreatment Surveillance: Diagnosis and Management of Recurrent Disease. AB - There has been a steady decline in breast cancer mortality that has led to a significant increase in the number of patients surviving breast cancer. We will review in this manuscript the evidence and guidelines for posttreatment surveillance of patients with breast cancer as well as the management options for patients who are diagnosed with local-regional and distant recurrences. PMID- 27681691 TI - Sonographic Examination of The Fetus Vis-a-Vis Shoulder Dystocia: A Vexing Promise. AB - Since antepartum and intrapartum risk factors are poor at identifying women whose labor is complicated by shoulder dystocia, sonographic examination of the fetus holds promise. Though there are several measurements of biometric parameters to identify the parturient who will have shoulder dystocia, none are currently clinically useful. Three national guidelines confirm that sonographic measurements do not serve as appropriate diagnostic tests to identify women who will have shoulder dystocia with or without concurrent injury. In summary, biometric measurements of the fetus should not be used to alter clinical management with the aim of averting shoulder dystocia. PMID- 27681689 TI - An investigation of the antiplatelet effects of succinobucol (AGI-1067). AB - Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet-platelet and platelet-vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10-5-10-4 M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress. PMID- 27681692 TI - An Update on the Acute Management of Shoulder Dystocia. AB - Shoulder dystocia continues to challenge obstetrical providers and therefore the management must evolve. The available literature demonstrates clear value in both simulation training and having a clear algorithmic approach. Similarly, the available literature suggests that delivery of the posterior arm should be prioritized. Several new techniques such as the Menticoglou maneuver, Gaskin's maneuver, and the posterior axilla sling traction technique offer obstetrical choices after more traditional techniques have failed. PMID- 27681694 TI - Breast Cancer Epidemiology and Risk Factors. AB - Between the years 2010 and 2012, the lifetime probability of developing female breast cancer was 12.3%, or approximately 1 in 8. Worldwide, breast cancer is the most common cancer in women. Survival is increasing. Between 2005 and 2011, the 5 year relative survival was found to be 89%. This is thought to be due to both the increase in utilization of population-wide screening, as well as advances in treatment. Less than 10% of breast cancers can be attributed to an inherited genetic mutation. Breast cancer is more commonly associated with environmental, reproductive, and lifestyle factors, some of which are potentially modifiable. PMID- 27681693 TI - Pathologic High-risk Lesions, Diagnosis and Management. AB - Percutaneous imaging-guided core needle biopsy (CNB) is a less invasive and less expensive alternative to surgical biopsy for the evaluation of breast lesions. After a CNB the radiologist determine if there is concordance between the pathology, imaging, and clinical findings. Patient management after CNB diagnosis of high-risk breast lesion varies. Surgical excision is warranted for lesions yielding a CNB diagnosis of ADH; however controversy exists regarding the need for surgical excision after CNB diagnosis of radial scar, papillary lesion, atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). Repeat CNB or surgical excision is warranted if histologic findings and imaging findings are discordant. PMID- 27681695 TI - Foreword. PMID- 27681696 TI - Advances, Pauses, and Future Opportunity for the Prevention of Venous Thromboembolism in the Trauma Population. PMID- 27681697 TI - The fibrolytic potentials of vitamin D and thymoquinone remedial therapies: insights from liver fibrosis established by CCl4 in rats. AB - BACKGROUND: Vitamin D (VitD) and thymoquinone (TQ) are nutraceutical agents with well-known immunomodulatory and hepatoprotective properties. This study measured whether VitD and TQ, individually or combined, could have direct fibrolytic activities and/or enhanced performance during remedial treatment of liver fibrosis established by CCl4 in rats. METHODS: Eighty five male Wistar rats were used as 10 negative controls (NC) and the remainders were distributed equally into 5 groups: short (S-PC) and long (L-PC) positive controls, TQ, VitD and VitD/TQ groups. CCl4 was injected for 7 weeks followed by a week of no intervention. TQ and/or VitD were given orally (3 days/week) from week 9 and euthanasia was at week 17 for all groups except the S-PC was at week 9. Following histopathological and digital image analyses, TGF-beta1, IL-6, IL-10, IL-22 and MMP-9 were measured by ELISA in liver homogenates while the corresponding cytokine receptors were measured by immunohistochemistry. The mRNA expressions of all molecules were measured by quantitative RT-PCR. RESULTS: Fibrosis was evident in both PC-groups and was significantly more advanced in the L-PC than S-PC, reaching to cirrhosis. The concentrations of TGF-beta1, IL-6, IL-22 and their receptors were significantly higher (P < 0.05) simultaneously with significantly lower (P < 0.05) concentrations of MMP-9, IL-10 and IL-10 receptors in the S-PC and L-PC than the NC-group. TQ and VitD monotherapies showed significantly less fibrosis than L-PC but were similar to S-PC. Both remedial monotherapies also resulted in significant decreases of TGF-beta1, IL-6, IL-22 and their receptors together with significant increases of MMP-9 and IL-10 system compared with S-PC and L-PC groups. Interestingly, dual therapy resulted in the most significant improvement in fibrosis score and index, yet was significantly higher (P < 0.05) than the NC-group, and concurred with the utmost significant restorations of all candidate genes and proteins. CONCLUSIONS: VitD and TQ exhibited comparable anti fibrogenic effects and modulated several pro- and anti-fibrotic mediators. Additionally, VitD/TQ dual therapy alleviated the previously established liver fibrosis simultaneously with significantly enhanced actions at the molecular level. More studies are required to explorer the therapeutic value of TQ and VitD against liver fibrosis in human. PMID- 27681698 TI - Association between polymorphisms of OGG1, EPHA2 and age-related cataract risk: a meta-analysis. AB - BACKGROUND: Evidences have identified the correlation of 8-oxoguanine DNA glycosylase-1 (OGG1) and eph-receptor tyrosine kinase-type A2 (EPHA2) polymorphisms in age-related cataract (ARC) risk. However, the results were not consistent. The objective of this study was to examine the role of these two gene polymorphisms in ARC susceptibility. METHODS: Eligible case-control studies published between January 2000 and 2015 were searched and retrieved in the electronic databases. The odds ratio with 95 % confidence interval (CI) was employed to calculate the strength of the relationship. RESULTS: We totally screened out six articles, including 5971 cataract patients and 4189 matched controls. Three variants were contained (OGG1 rs1052133; EPHA2 rs7543472 and rs11260867). For OGG1 rs1052133, we detected a significant correlation between OGG1 polymorphism and ARC risk under the heterogenous model (CG vs. CC: OR = 1.34, 95 % CI = 1.06-1.70, P = 0.01) and dominant model (GG+CG vs. CC: OR = 1.45, 95 % CI = 1.16-1.81, P = 0.001), especially in patients with cortical cataract of subgroup analysis by phenotypes (P < 0.05). For EPHA2 rs7543472 and rs11260867, we did not find a positive association between these two mutations and ARC susceptibility in total cases. Subgroup analysis by phenotypes of cataract showed that only in cortical cataract, genotypes of rs7543472 under the allele model, homogenous model and recessive model; genotypes of rs11260867 under the heterogenous model and dominant model were associated with ARC risk. CONCLUSIONS: OGG1 rs1052133 (CG and CG+GG genotypes) might be risk factor for ARC, particularly in cortical cataract risk. EPHA2 rs7543472 (T allele and TT genotype) and rs11260867 (CG and GG+CG genotypes) might be associated with cortical cataract. PMID- 27681699 TI - Fatal Zika Virus Infection with Secondary Nonsexual Transmission. PMID- 27681700 TI - Profiles of Stimulus-Frequency Otoacoustic Emissions from 0.5 to 20 kHz in Humans. AB - The characteristics of human otoacoustic emissions (OAEs) have not been thoroughly examined above the standard audiometric frequency range (>8 kHz). This is despite the fact that deterioration of cochlear function often starts at the basal, high-frequency end of the cochlea before progressing apically. Here, stimulus-frequency OAEs (SFOAEs) were obtained from 0.5 to 20 kHz in 23 young, audiometrically normal female adults and three individuals with abnormal audiograms, using a low-to-moderate probe level of 36 dB forward pressure level (FPL). In audiometrically normal ears, SFOAEs were measurable at frequencies approaching the start of the steeply sloping high-frequency portion of the audiogram (~12-15 kHz), though their amplitudes often declined substantially above ~7 kHz, rarely exceeding 0 dB SPL above 8 kHz. This amplitude decline was typically abrupt and occurred at a frequency that was variable across subjects and not strongly related to the audiogram. In contrast, certain ears with elevated mid-frequency thresholds but regions of normal high-frequency sensitivity could possess surprisingly large SFOAEs (>10 dB SPL) above 7 kHz. When also measured, distortion-product OAEs (DPOAEs) usually remained stronger at higher stimulus frequencies and mirrored the audiogram more closely than SFOAEs. However, the high-frequency extent of SFOAE and DPOAE responses was similar when compared as a function of the response frequency, suggesting that middle ear transmission may be a common limiting factor at high frequencies. Nevertheless, cochlear factors are more likely responsible for complexities observed in high frequency SFOAE spectra, such as abrupt amplitude changes and narrowly defined response peaks above 10 kHz, as well as the large responses in abnormal ears. These factors may include altered cochlear reflectivity due to subtle damage or the reduced spatial extent of the SFOAE generation region at the cochlear base. The use of higher probe levels is necessary to further evaluate the characteristics and potential utility of high-frequency SFOAE measurements. PMID- 27681701 TI - Antimuscarinic Medication Use in Elderly Patients with Overactive Bladder. AB - BACKGROUND: Antimuscarinic medications are the first-line pharmacological treatment for overactive bladder (OAB); however, little is known about the utilization pattern of antimuscarinic agents in elderly patients with OAB. OBJECTIVE: This study examined the prevalence and predictors of antimuscarinic medication prescribing in elderly patients with OAB, using national ambulatory survey data. METHODS: This cross-sectional study utilized the 2009-2010 National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Medical Care Survey. The study included patients aged >=65 years diagnosed with OAB based on the International Classification of Diseases. Antimuscarinic medications were operationally defined using the American Hospital Formulary Service classification and identified using Multum Lexicon codes. Descriptive statistics using sampling weights were used to estimate the prevalence of antimuscarinic medication prescription, while multivariable logistic regression within the conceptual framework of the Anderson Behavioral Model was used to identify the factors associated with antimuscarinic medication prescription in elderly patients with OAB. RESULTS: According to the national surveys, 2.18 million (95 % confidence interval [CI] 1.62-2.75) elderly outpatient visits were made for OAB, of which 0.90 million (41.43 %) visits involved prescribing of antimuscarinic medications. The most frequently prescribed drugs were solifenacin (14.25 %), oxybutynin (10.50 %), and tolterodine (6.89 %). Multivariable analysis revealed that patients >=85 years of age (odds ratio [OR] 3.50, 95 % CI 1.23-9.92) were more likely to receive antimuscarinic medications, and the South region (OR 2.78, 95 % CI 1.01-7.66) increased the likelihood of receiving antimuscarinic medications in elderly patients with OAB. CONCLUSIONS: This study found that antimuscarinic medications are commonly prescribed for elderly patients with OAB and there is variation in antimuscarinic use across age and region. PMID- 27681703 TI - Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations. AB - Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol co-secretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries. While the prevalence of KCNJ5 mutations is approximately 40% in Western countries, 37 APA cases (78.7%) showed mutations: 26 with p.G151R and 11 with p.L168R. Although a significant gender difference has been reported in the frequency of KCNJ5 mutations in Europe, we did not find any gender difference. However, the phenotypes of Japanese patients with mutations were similar to those of patients in Western countries; patients were younger and had higher plasma aldosterone levels, lower potassium levels, and higher diastolic blood pressure. Reflecting these phenotypes, APAs with mutations had higher CYP11B2 mRNA levels. However, in contrast to APAs in Western countries, Japanese APAs with mutations showed lower CYP11B1, CYP17A1, and CYP11A1 mRNA levels. These findings demonstrated that Japanese APA patients may have distinct features including a higher prevalence of KCNJ5 mutations, no gender difference in the frequency of these mutations, and characteristics similar to the zona glomerulosa. PMID- 27681702 TI - Effects of Renal Impairment on Steady-State Plasma Concentrations of Rivastigmine: A Population Pharmacokinetic Analysis of Capsule and Patch Formulations in Patients with Alzheimer's Disease. AB - INTRODUCTION: The glomerular filtration rate (GFR), a measure of renal function, decreases by approximately 10 mL/min every 10 years after the age of 40 years, which could lead to the accumulation of drugs and/or renal toxicity. Pharmacokinetic studies of drugs excreted both renally and non-renally are desirable in patients with impaired renal function, defined by parameters including estimated GFR (eGFR) and creatinine clearance (CLCR). OBJECTIVE: We describe here a population pharmacokinetic analysis of the possible effects of renal impairment on steady-state plasma concentrations of rivastigmine and its metabolite NAP226-90 after rivastigmine patch (5 cm2 [4.6 mg/24 h], 10 cm2 [9.5 mg/24 h], 15 cm2 [13.3 mg/24 h], and 20 cm2 [17.4 mg/24 h]) and capsule (1.5, 3, 4.5, and 6 mg/12 h) treatment in patients with Alzheimer's disease. METHODS: The data used to conduct the current pharmacokinetic analysis were obtained from the pivotal phase III, 24-week, multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group study (IDEAL). One blood sample was collected from each patient at steady-state to measure plasma concentrations of rivastigmine and NAP226-90 using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The steady-state plasma concentrations of rivastigmine and NAP226-90 were plotted against CLCR and eGFR data, and boxplots were constructed after stratification by renal function. RESULTS: The two groups (mild/no renal impairment vs. moderate/severe/end-stage renal impairment) showed comparable demographic covariates for all patch sizes and capsule doses. No correlation was observed between CLCR or eGFR and plasma concentrations of rivastigmine or NAP226 90. Boxplots of concentrations of rivastigmine or NAP226-90 for each dose largely overlapped for patch and capsule. Additionally, model-based estimates of plasma concentrations adjusted for body weight yielded similar results. CONCLUSION: The results of this study show that renal function does not affect rivastigmine or NAP226-90 steady-state plasma concentrations, and no dose adjustment in patients with renal impairment is required. CLINICALTRIALS.GOV: NCT00099242. PMID- 27681704 TI - Usefulness of urinary glucose excretion after oral glucose tolerance testing to detect insulin secretion failure before the onset of diabetes mellitus. AB - Sodium-glucose cotransporter 2 inhibitors are commonly used to promote urinary glucose excretion (UGE). However, it remains unclear how UGE reflects glucose metabolism in the natural history of diabetes. Thus, we retrospectively reviewed the prediabetes medical records of 64 patients who had undergone 75-g oral glucose tolerance testing (OGTT) with measurements of UGE at 0 min, 60 min, and 120 min. The mean age and glycated hemoglobin levels were 46 +/- 10 years and 5.6 +/- 0.3%, respectively. The median UGE (60 min + 120 min) value was 16.8 mg ([interquartile range]: [10.5-150.0 mg]). Thus, we categorized 16 patients as having high UGE (>=150.0 mg) and 48 patients as having low UGE (<150.0 mg). As compared with the low UGE group, the high UGE group exhibited a significantly lower median insulinogenic index (0.23 [0.12-0.35] vs. 0.56 [0.31-1.06], p = 0.001) and homeostasis model assessment of beta-cell function value (46 [26-67] vs. 66 [41-85], p = 0.028). The log-transformed insulinogenic index exhibited a significant inverse association with log-transformed UGE (60 min + 120 min) (r = 0.50, p < 0.001). The association between higher UGE and lower insulinogenic index was also observed in a subgroup analysis of patients with plasma glucose levels of >=160 mg/dL during the OGTT. Therefore, UGE measurements after OGTT may provide a useful clinical marker for detecting insulin secretion failure and advancing preventive and therapeutic interventions among populations with a high risk of developing diabetes. PMID- 27681705 TI - ABO type and bleeding during adult ECMO. PMID- 27681707 TI - Adverse Events in Childhood as a Risk Factor for Elevated BMI among People with Schizophrenia and Bipolar Disorder. AB - Diseases of obesity have become a major cause of morbidity and mortality among people with schizophrenia and bipolar disorder. Childhood adversity has been associated with adult obesity in the general public, but has not been examined among people with mental illness. This study used a secondary analysis to examine childhood adversity and body mass index in people with schizophrenia and bipolar disorder. Among females, a history of physical abuse from parents or paternal emotional neglect was associated with an increased risk for obesity (OR = 3.34 and 2.44, respectively). PMID- 27681706 TI - Venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock post-cardiac arrest. AB - PURPOSE: To describe the characteristics, outcomes, and risk factors associated with poor outcome of venoarterial extracorporeal membrane oxygenation (VA-ECMO) treated patients with refractory shock post-cardiac arrest. METHODS: We retrospectively analyzed data collected prospectively (March 2007-January 2015) in a 26-bed tertiary hospital intensive care unit. All patients implanted with VA ECMO for refractory cardiogenic shock after successful resuscitation from cardiac arrest were included. Refractory cardiac arrest patients, given VA-ECMO under cardiopulmonary resuscitation, were excluded. RESULTS: Ninety-four patients received VA-ECMO for refractory shock post-cardiac arrest. Their hospital and 12 month survival rates were 28 and 27 %, respectively. All 1-year survivors were cerebral performance category 1. Multivariable analysis retained INR >2.4 (OR 4.9; 95 % CI 1.4-17.2), admission SOFA score >14 (OR 5.3; 95 % CI 1.7-16.5), and shockable rhythm (OR 0.3; 95 % CI 0.1-0.9) as independent predictors of hospital mortality, but not SAPS II, out-of-hospital cardiac arrest score, or other cardiac arrest variables. Only 10 % of patients with an admission SOFA score >14 survived, whereas 50 % of those with scores <=14 were alive at 1 year. Restricting the analysis to the 67 patients with out-of-hospital cardiac arrest of coronary cause yielded similar results. CONCLUSION: Among 94 patients implanted with VA-ECMO for refractory cardiogenic shock post-cardiac arrest resuscitation, the 24 (27 %) 1-year survivors had good neurological outcomes, but survival was significantly better for patients with admission SOFA scores <14, shockable rhythm, and INR <=2.4. VA-ECMO might be considered a rescue therapy for patients with refractory cardiogenic shock post-cardiac arrest resuscitation. PMID- 27681709 TI - Snowball Vs. House-to-House Technique for Measuring Annual Incidence of Kala-azar in the Higher Endemic Blocks of Bihar, India: A Comparison. AB - BACKGROUND: Visceral Leishmaniasis, commonly known as kala-azar, is widely prevalent in Bihar. The National Kala-azar Control Program has applied house-to house survey approach several times for estimating Kala-azar incidence in the past. However, this approach includes huge logistics and operational cost, as occurrence of kala-azar is clustered in nature. The present study aims to compare efficiency, cost and feasibility of snowball sampling approach to house-to-house survey approach in capturing kala-azar cases in two endemic districts of Bihar, India. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional study was conducted in two highly endemic Primary Health Centre (PHC) areas, each from two endemic districts of Bihar, India. Snowball technique (used to locate potential subjects with help of key informants where subjects are hard to locate) and house-to-house survey technique were applied to detect all the new cases of Kala-azar during a defined reference period of one year i.e. June, 2010 to May, 2011. The study covered a total of 105,035 households with 537,153 populations. Out of total 561 cases and 17 deaths probably due to kala-azar, identified by the study, snowball sampling approach captured only 221 cases and 13 deaths, whereas 489 cases and 17 deaths were detected by house-to-house survey approach. Higher value of McNemar's chi2 statistics (64; p<0.0001) for house-to-house survey approach than snowball sampling and relative difference (>1) indicates that most of the kala-azar cases missed by snowball sampling were captured by house-to house approach with 13% of omission. CONCLUSION/SIGNIFICANCE: Snowball sampling was not found sensitive enough as it captured only about 50% of VL cases. However, it captured about 77% of the deaths probably due to kala-azar and was found more cost-effective than house-to-house approach. Standardization of snowball approach with improved procedure, training and logistics may enhance the sensitivity of snowball sampling and its application in national Kala-azar elimination programme as cost-effective approach for estimation of kala-azar burden. PMID- 27681708 TI - A spatial model of Wild Poliovirus Type 1 in Kano State, Nigeria: calibration and assessment of elimination probability. AB - BACKGROUND: Since the launch of the Global Polio Eradication Initiative, all but three countries (Nigeria, Pakistan, and Afghanistan) have apparently interrupted all wild poliovirus (WPV) transmission, and only one of three wild serotypes has been reported globally since 2012. Countrywide supplemental immunization campaigns in Nigeria produced dramatic reduction in WPV Type 1 paralysis cases since 2010 compared to the 2000's, and WPV1 has not been observed in Nigeria since July 24, 2014. This article presents the development and calibration of a spatial metapopulation model of wild poliovirus Type 1 transmission in Kano State, Nigeria, which was the location of the most recent WPV1 case and 5 out of 6 of the reported WPV1 paralytic cases in Nigeria in 2014. METHODS: The model is calibrated to data on the case counts and age at onset of paralysis from 2003 2009. The features of the data drive model development from a simple susceptible exposed-infective-recovered (SEIR) model to a spatial metapopulation model featuring seasonal forcing and age-dependent transmission. The calibrated parameter space is then resampled, projected forward, and compared to more recent case counts to estimate the probability that Type 1 poliovirus has been eliminated in Kano state. RESULTS: The model indicates a 91 % probability that Type 1 poliovirus has been eliminated from Kano state as of October 2015. This probability rises to >99 % if no WPV1 paralysis cases are detected for another year. The other states in Nigeria have experienced even longer case-free periods (the only other state with a WPV1 case was Yobe, on April 19, 2014), and Nigeria is the last remaining country in Africa to experience endemic WPV1 transmission, so these results can be interpreted as an upper bound on the probability that WPV1 transmission is currently interrupted continent-wide. CONCLUSIONS: While the results indicate optimism that WPV1 transmission has been interrupted in Kano state, the model also assumes that frequent SIAs with high coverage continue to take place in Kano state through the end of the certification period. We conclude that though WPV1 appears to be on the brink of continent-wide elimination (WHO officially removed Nigeria from the list of polio-endemic countries on September 25, 2015), it is important for the polio program to maintain vigilance in surveillance and vaccination activities to prevent WPV1 resurgence through the WHO's 3-year eradication certification period. PMID- 27681710 TI - Do previous sports experiences influence the effect of an enrichment programme in basketball skills? AB - The aim of this study was to examine the effect of an enrichment programme in motor, technical and tactical basketball skills, when accounting for the age of youth sport specialisation. Seventy-six college students (age: M = 20.4, SD = 1.9) were allocated according to three different paths: (i) non-structured (n = 14), (ii) early specialisation (n = 34), and (iii) late specialisation (n = 28), according to information previously provided by the participants about the quantity and type of sporting activities performed throughout their sporting careers. Then, the participants of each path were randomly distributed across control and experimental groups. Variables under study included agility, technical skills circuit, as well as tactical actions performed in a 4-on-4 full court basketball game. The results indicated improvements in the early and late specialisation paths namely in the experimental training groups. However, the late specialisation path revealed larger benefits, in contrast with the non structured path, which showed less sensitivity to the enrichment programme, mostly sustained in physical literacy and differential learning. Higher improvements were observed in agility, and also in reducing the number of unsuccessful actions performed during the game. Overall, this study provided evidence of how early sports experiences affect basketball skill acquisition and contribute to adapt to new contexts with motor and technical-tactical challenges. In addition, a path supported by late specialisation might present several advantages in sport performance achievement. PMID- 27681711 TI - Adaptation of the Grasha Riechman Student Learning Style Survey and Teaching Style Inventory to assess individual teaching and learning styles in a quality improvement collaborative. AB - BACKGROUND: NIATx200, a quality improvement collaborative, involved 201 substance abuse clinics. Each clinic was randomized to one of four implementation strategies: (a) interest circle calls, (b) learning sessions, (c) coach only or (d) a combination of all three. Each strategy was led by NIATx200 coaches who provided direct coaching or facilitated the interest circle and learning session interventions. METHODS: Eligibility was limited to NIATx200 coaches (N = 18), and the executive sponsor/change leader of participating clinics (N = 389). Participants were invited to complete a modified Grasha Riechmann Student Learning Style Survey and Teaching Style Inventory. Principal components analysis determined participants' preferred learning and teaching styles. RESULTS: Responses were received from 17 (94.4 %) of the coaches. Seventy-two individuals were excluded from the initial sample of change leaders and executive sponsors (N = 389). Responses were received from 80 persons (25.2 %) of the contactable individuals. Six learning profiles for the executive sponsors and change leaders were identified: Collaborative/Competitive (N = 28, 36.4 %); Collaborative/Participatory (N = 19, 24.7 %); Collaborative only (N = 17, 22.1 %); Collaborative/Dependent (N = 6, 7.8 %); Independent (N = 3, 5.2 %); and Avoidant/Dependent (N = 3, 3.9 %). NIATx200 coaches relied primarily on one of four coaching profiles: Facilitator (N = 7, 41.2 %), Facilitator/Delegator (N = 6, 35.3 %), Facilitator/Personal Model (N = 3, 17.6 %) and Delegator (N = 1, 5.9 %). Coaches also supported their primary coaching profiles with one of eight different secondary coaching profiles. CONCLUSIONS: The study is one of the first to assess teaching and learning styles within a QIC. Results indicate that individual learners (change leaders and executive sponsors) and coaches utilize multiple approaches in the teaching and practice-based learning of quality improvement (QI) processes. Identification teaching profiles could be used to tailor the collaborative structure and content delivery. Efforts to accommodate learning styles would facilitate knowledge acquisition enhancing the effectiveness of a QI collaborative to improve organizational processes and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00934141 Registered July 6, 2009. Retrospectively registered. PMID- 27681712 TI - Correlation of Expression of Breast Biomarkers in Primary and Metastatic Breast Carcinomas: A Single-Institution Experience. AB - OBJECTIVE: Changes in the status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in metastatic breast carcinomas are frequently reported. We examined the change in the status of biomarkers in metastatic breast carcinomas. STUDY DESIGN: This study cohort was composed of 137 metastatic breast carcinomas (58 surgical and 79 cytological specimens) with existing primary tumors during a study period from 2013 to 2015. RESULTS: The overall change rates in metastases were 9, 21 and 6% for ER, PR and HER2, respectively. All changes were from positive in the primary tumor to negative in the metastases. The ER change rate was significantly higher in the cytological than in the surgical metastases. Six of 14 cytological metastases with positive HER2 in primary tumors showed a change in HER2 status, including 5 fluid specimens and 1 fine-needle aspiration (FNA); the other 8 had no change in HER2 status, and included 7 FNAs and 1 fluid specimen. CONCLUSION: The significant percentage of cases with a change in biomarker status supports the recommendation by the College of American Pathologists to test breast biomarkers in metastases. HER2 status change was mostly identified in fluid specimens; however, the small sample size in our cohort and the fact that HER2 fluorescence in situ hybridization was not performed may warrant further studies. PMID- 27681713 TI - Novel Diterpenoids from the Twigs of Podocarpus nagi. AB - Phytochemical investigation of the twigs of Podocarpus nagi (Podocarpaceae) led to the isolation of two new abietane-type diterpenoids, named 1beta,16 dihydroxylambertic acid (1) and 3beta,16-dihydroxylambertic acid (2), along with two new ent-pimarane-type diterpenoids, named ent-2beta,15,16,18 tetrahydroxypimar-8(14)-ene (3) and ent-15-oxo-2beta,16,18-trihydroxypimar-8(14) ene (4). Their respective structures were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, IR, CD, and HR-ESI-MS. This is the first time ent-pimarane-type diterpenoids from the genus Podocarpus has been reported. All four new compounds were tested for cytotoxic activity. The MTT assay results showed that compounds 3 and 4 significantly inhibited the proliferation of human cervical cancer Hela cells, human lung cancer A549 cells, and human breast cancer MCF-7 cells at a concentration of 10 MUM. Furthermore, using the lipopolysaccharide (LPS)-stimulated RAW264.7 cells, compounds 2 and 4 were found to significantly inhibit nitrogen oxide (NO) production with IC50 values of 26.5 +/- 6.1 and 17.1 +/- 1.5 MUM, respectively. PMID- 27681714 TI - Antiprotozoal and Antiglycation Activities of Sesquiterpene Coumarins from Ferula narthex Exudate. AB - The exudate of Ferula narthex Boiss. (Apiaceae) is widely used in the Indian subcontinent as a spice and because of its health effects. Six sesquiterpene coumarins have been isolated from this exudate: feselol, ligupersin A, asacoumarin A, 8'-O-acetyl-asacoumarin A, 10'R-karatavacinol and 10'R-acetyl karatavacinol. Based on its use in infectious and diabetic conditions, the isolated constituents were evaluated for antimicrobial and antiglycation activities. Some compounds showed activity against protozoal parasites, asacoumarin A being the most active one against Plasmodium falciparum K1 (IC50 1.3 MUM). With regard to antiglycation activity, in the BSA-glucose test, ligupersin A displayed the highest activity (IC50 0.41 mM), being more active than the positive control aminiguanidine (IC50 1.75 mM). In the BSA-MGO assay, the highest activity was shown by 8'-O-acetyl-asacoumarin A (IC50 1.03 mM), being less active than aminoguanidine (IC50 0.15 mM). Hence, the antiglycation activity of the isolated constituents was due to both oxidative and non-oxidative modes of inhibition. PMID- 27681715 TI - Acacetin Protects Mice from Staphylococcus aureus Bloodstream Infection by Inhibiting the Activity of Sortase A. AB - Staphylococcus aureus (S. aureus) is a major cause of infection in hospitals and communities. Widespread dissemination of multi-drug resistant S. aureus is a serious threat to the health of humans and animals. An anti-virulence strategy has been widely considered as an alternative therapeutic approach. Inhibitors of virulence factors are able to treat S. aureus infections without influencing the growth or viability of bacteria and rarely lead to bacterial resistance. Sortase A (SrtA) is a membrane-associated cysteine transpeptidase that catalyzes up to 25 surface proteins that covalently bind to cell wall peptidoglycans. In S. aureus, most of these surface proteins have been identified as important virulence factors that are vital in bacterial pathogenesis. In the present study, we show that acacetin, a natural flavonoid compound, inhibits the activity of SrtA in S. aureus (IC50 = 36.46 +/- 4.69 MUg/mL, 128 MUM) which affects the assembly of protein A (SpA) to cell walls and reduces the binding of S. aureus to fibrinogen (Fg). The mechanism of the interaction between acacetin and SrtA were preliminarily discussed using molecular dynamics simulations. The results suggested that acacetin adopted a compact conformation binding at the pocket of the SrtA via residues Arg-139 and Lys-140. By performing an animal infection model, we demonstrated that acacetin was able to protect mice from renal abscess formation induced by S. aureus and significantly increased survival rates. Taken together, these findings suggest that acacetin may be a promising candidate for the development of anti-S. aureus drugs. PMID- 27681716 TI - Terminamines K-S, Antimetastatic Pregnane Alkaloids from the Whole Herb of Pachysandra terminalis. AB - Nine new pregnane alkaloids (1-9), together with eight known alkaloids (10-17), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates were examined for their ability to inhibit the migration of MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Alkaloids 1, 5, 7, 9, 12, and 17 presented significant anti-metastasis activities compared with the positive reagent, LY294002. PMID- 27681717 TI - Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes. AB - To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPbetaA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs. The peptides were delivered into their cytosol. Administration of OVA-I-loaded MGlu-HPG-modified liposomes to mice bearing OVA expressing E.G7-OVA tumors induced the activation of OVA-specific CTLs much more efficiently than the administration of free OVA-I peptide did. Mice strongly rejected E.G7-OVA cells after immunization with OVA-I peptide-loaded MGlu-HPG liposomes, although mice treated with free OVA-I peptide only slightly rejected the cells. Furthermore, efficient suppression of tumor volume was observed when tumor-bearing mice were immunized with OVA-I-peptide-loaded liposomes. Immunization with OVA-II-loaded MGlu-HPG-modified liposomes exhibited much lower tumor-suppressive effects. Results indicate that MGlu-HPG liposomes might be useful for improvement of CTL-inducing peptides for efficient cancer immunotherapy. PMID- 27681718 TI - Effects of Sanguis Draconis on Perforator Flap Survival in Rats. AB - Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was carried out on 20 rats that were divided into two groups, a control group (n = 10) and an EESD group (n = 10). All the rats underwent a perforator flap surgery, after which post-operative abdominal compressions of EESD were given to the EESD group for seven days, while the control group received saline. Flap survival percentages were determined after seven days, and were found to be significantly higher in the EESD group than in the control group. Results of laser Doppler flowmetry (LDF) showed that perforator flaps in the EESD group had higher perfusion values than those of the control group. The flap tissues were stained with hematoxylin and eosin, followed by immunohistochemical evaluation. Superoxide dismutase (SOD) expression and micro-vessel development markedly increased in the EESD group, while malondialdehyde (MDA) levels decreased. This is the first study to investigate the effect of sanguis draconis on perforator flap survival. Our results demonstrate that sanguis draconis can improve perforator flap survival in rats by promoting microvessel regeneration and blood perfusion. PMID- 27681719 TI - Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma. AB - Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin, the most abundant flavonoid, has been shown to have anti-ulcer, anti-cancer, antioxidant, and anti-inflammatory properties. Latent Epstein-Barr virus (EBV) infection can lead to serious malignancies, such as, Burkitt's lymphoma, Hodgkin's disease and gastric carcinoma(GC), and (Epstein-Barr virus associated gastric carcinoma) EBVaGC is one of the most common EBV-associated cancers. In this study, the authors first examined the anti-cancer effects of quercetin and isoliquiritigenin in vivo xenograft animal models implanted with EBV(+) human gastric carcinoma (SNU719) or EBV(-) human gastric carcinoma (MKN74), and then explored the molecular mechanisms responsible for their anti-cancer activities. The results obtained showed that anti-cancer effect of quercetin was greater than isoliquiritigenin in mice injected with EBV(+) human gastric carcinoma (SNU719) cells. On the other hand, quercetin and isoliquiritigenin had similar anti-cancer effects in mice injected with EBV(-) human gastric carcinoma (MKN74) cells. Interestingly, quercetin inhibited EBV viral protein expressions, including EBNA 1 and LMP-2 proteins in tumor tissues from mice injected with EBV(+) human gastric carcinoma. Quercetin more effectively induced p53-dependent apoptosis than isoliquiritigenin in EBV(+) human gastric carcinoma, and this induction was correlated with increased expressions of the cleaved forms of caspase-3, -9, and Parp. In EBV(-)human gastric carcinoma (MKN74), both quercetin and isoliquiritigenin induced the expressions of p53, Bax, and Puma and the cleaved forms of caspase-3 and -9 and Parp at similar levels. PMID- 27681720 TI - The Structure-Antimicrobial Activity Relationships of a Promising Class of the Compounds Containing the N-Arylpiperazine Scaffold. AB - This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened against Mycobacterium avium subsp. paratuberculosis CIT03, M. smegmatis ATCC 700084, M. kansasii DSM 44162, M. marinum CAMP 5644, Staphylococcus aureus ATCC 29213, methicillin-resistant S. aureus 63718, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Candida albicans CCM 8261, C. parapsilosis CCM 8260 and C. krusei CCM 8271, respectively, by standardized microdilution methods. The eventual antiproliferative (cytotoxic) impact of those compounds was examined on a human monocytic leukemia THP-1 cell line, as a part of the biological study. Promising potential against M. kansasii was found for 1-[3-(3-ethoxyphenylcarbamoyl)oxy-2 hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride (MIC = 31.75 MUM), which was comparable to the activity of isoniazid (INH; MIC = 29.17 MUM). Moreover, 1-{2-hydroxy-3-(3-methoxyphenylcarbamoyl)oxy)propyl}-4-(4 fluorophenyl)piperazin-1-ium chloride was even more effective (MIC = 17.62 MUM) against given mycobacterium. Among the tested N-arylpiperazines, 1-{2-hydroxy-3 (4-methoxyphenylcarbamoyl)oxy)propyl}-4-(3-trifluorometh-ylphenyl)piperazin-1-ium chloride was the most efficient against M. marinum (MIC = 65.32 MUM). One of the common features of all investigated substances was their insignificant antiproliferative (i.e., non-cytotoxic) effect. The study discussed structure antimicrobial activity relationships considering electronic, steric and lipophilic properties. PMID- 27681721 TI - Nanoemulsion Formulations of Fungicide Tebuconazole for Agricultural Applications. AB - Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (RO/S) were evaluated in the range of 1-90 and 1-10 wt %, respectively. The study was carried out with an organic phase (OP) consisting of an acetone/glycerol mixture containing TBZ at a concentration of 5.4 wt % and Tween 80 (TW80) as a nonionic and Agnique BL1754 (AG54) as a mixture of nonionic and anionic surfactants. The process involved a large dilution of a bicontinuous microemulsion (ME) into an aqueous phase (AP). Pseudo-ternary phase diagrams of the OP//TW80//AP and OP//AG54//AP systems at T = 25 degrees C were determined to map ME regions; these were in the range of 0.49 0.90, 0.01-0.23, and 0.07-0.49 of OP, AP, and surfactant, respectively. Optical microscope images helped confirm ME formation and system viscosity was measured in the range of 25-147 cP. NEs with drop sizes about 9 nm and 250 nm were achieved with TW80 and AG54, respectively. An innovative low-energy method was used to develop nanopesticide TBZ formulations based on nanoemulsion (NE) technology. The surface tension of the studied systems can be lowered 50% more than that of pure water. This study's proposed low-energy NE formulations may prove useful in sustainable agriculture. PMID- 27681722 TI - MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer. AB - MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC. PMID- 27681725 TI - Fabrication and Mechanical Characterization of Hydrogel Infused Network Silk Scaffolds. AB - Development and characterization of porous scaffolds for tissue engineering and regenerative medicine is of great importance. In recent times, silk scaffolds were developed and successfully tested in tissue engineering and drug release applications. We developed a novel composite scaffold by mechanical infusion of silk hydrogel matrix into a highly porous network silk scaffold. The mechanical behaviour of these scaffolds was thoroughly examined for their possible use in load bearing applications. Firstly, unconfined compression experiments show that the denser composite scaffolds displayed significant enhancement in the elastic modulus as compared to either of the components. This effect was examined and further explained with the help of foam mechanics principles. Secondly, results from confined compression experiments that resemble loading of cartilage in confinement, showed nonlinear material responses for all scaffolds. Finally, the confined creep experiments were performed to calculate the hydraulic permeability of the scaffolds using soil mechanics principles. Our results show that composite scaffolds with some modifications can be a potential candidate for use of cartilage like applications. We hope such approaches help in developing novel scaffolds for tissue engineering by providing an understanding of the mechanics and can further be used to develop graded scaffolds by targeted infusion in specific regions. PMID- 27681724 TI - Interactions between Two Different G Protein-Coupled Receptors in Reproductive Hormone-Producing Cells: The Role of PACAP and Its Receptor PAC1R. AB - Gonadotropin-releasing hormone (GnRH) and gonadotropins are indispensable hormones for maintaining female reproductive functions. In a similar manner to other endocrine hormones, GnRH and gonadotropins are controlled by their principle regulators. Although it has been previously established that GnRH regulates the synthesis and secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH)-both gonadotropins-from pituitary gonadotrophs, it has recently become clear that hypothalamic GnRH is under the control of hypothalamic kisspeptin. Prolactin, which is also known as luteotropic hormone and is released from pituitary lactotrophs, stimulates milk production in mammals. Prolactin is also regulated by hypothalamic factors, and it is thought that prolactin synthesis and release are principally under inhibitory control by dopamine through the dopamine D2 receptor. In addition, although it remains unknown whether it is a physiological regulator, thyrotropin-releasing hormone (TRH) is a strong secretagogue for prolactin. Thus, GnRH, LH and FSH, and prolactin are mainly regulated by hypothalamic kisspeptin, GnRH, and TRH, respectively. However, the synthesis and release of these hormones is also modulated by other neuropeptides in the hypothalamus. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hypothalamic peptide that was first isolated from sheep hypothalamic extracts based on its ability to stimulate cAMP production in anterior pituitary cells. PACAP acts on GnRH neurons and pituitary gonadotrophs and lactotrophs, resulting in the modulation of their hormone producing/secreting functions. Furthermore, the presence of the PACAP type 1 receptor (PAC1R) has been demonstrated in these cells. We have examined how PACAP and PAC1R affect GnRH- and pituitary hormone-secreting cells and interact with their principle regulators. In this review, we describe our understanding of the role of PACAP and PAC1R in the regulation of GnRH neurons, gonadotrophs, and lactotrophs, which are regulated mainly by kisspeptin, GnRH, and TRH, respectively. PMID- 27681723 TI - The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury. AB - Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), triglyceride (TG), malondialdehyde (MDA), and decreased total protein (TP). Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage. PMID- 27681726 TI - Global Transcriptomic Analysis of Targeted Silencing of Two Paralogous ACC Oxidase Genes in Banana. AB - Among 18 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase homologous genes existing in the banana genome there are two genes, Mh-ACO1 and Mh-ACO2, that participate in banana fruit ripening. To better understand the physiological functions of Mh-ACO1 and Mh-ACO2, two hairpin-type siRNA expression vectors targeting both the Mh-ACO1 and Mh-ACO2 were constructed and incorporated into the banana genome by Agrobacterium-mediated transformation. The generation of Mh-ACO1 and Mh-ACO2 RNAi transgenic banana plants was confirmed by Southern blot analysis. To gain insights into the functional diversity and complexity between Mh-ACO1 and Mh-ACO2, transcriptome sequencing of banana fruits using the Illumina next-generation sequencer was performed. A total of 32,093,976 reads, assembled into 88,031 unigenes for 123,617 transcripts were obtained. Significantly enriched Gene Oncology (GO) terms and the number of differentially expressed genes (DEGs) with GO annotation were 'catalytic activity' (1327, 56.4%), 'heme binding' (65, 2.76%), 'tetrapyrrole binding' (66, 2.81%), and 'oxidoreductase activity' (287, 12.21%). Real-time RT-PCR was further performed with mRNAs from both peel and pulp of banana fruits in Mh-ACO1 and Mh-ACO2 RNAi transgenic plants. The results showed that expression levels of genes related to ethylene signaling in ripening banana fruits were strongly influenced by the expression of genes associated with ethylene biosynthesis. PMID- 27681727 TI - Disruption of Membranes of Extracellular Vesicles Is Necessary for ELISA Determination of Urine AQP2: Proof of Disruption and Epitopes of AQP2 Antibodies. AB - Aquaporin-2 (AQP2) is present in urine extracellular vesicles (EVs) and is a useful biomarker for water balance disorders. We previously found that pre treatment of urine with alkali/detergent or storage at -25 degrees C is required for enzyme-linked immunosorbent assay (ELISA) measurement. We speculated that disruptions of EVs membranes are necessary to allow for the direct contact of antibodies with their epitopes. Human urine EVs were prepared using an ultracentrifugation method. Urine EV samples were stored at different temperatures for a week. Electron microscopy showed abundant EVs with diameters of 20-100 nm, consistent with those of exosomes, in normal urine, whereas samples from alkali/detergent pre-treated urine showed fewer EVs with large swollen shapes and frequent membrane disruptions. The abundance and structures of EVs were maintained during storage at -80 degrees C, but were severely damaged at 25 degrees C. Binding and competitive inhibition assays showed that epitopes of monoclonal antibody and polyclonal antibody were the hydrophilic Loop D and C terminus of AQP2, respectively, both of which are present on the inner surface of EVs. Thus, urine storage at -25 degrees C or pre-treatment with alkali/detergent disrupt EVs membranes and allow AQP2 antibodies to bind to their epitopes located inside EVs. PMID- 27681728 TI - Strain Modal Analysis of Small and Light Pipes Using Distributed Fibre Bragg Grating Sensors. AB - Vibration fatigue failure is a critical problem of hydraulic pipes under severe working conditions. Strain modal testing of small and light pipes is a good option for dynamic characteristic evaluation, structural health monitoring and damage identification. Unique features such as small size, light weight, and high multiplexing capability enable Fibre Bragg Grating (FBG) sensors to measure structural dynamic responses where sensor size and placement are critical. In this paper, experimental strain modal analysis of pipes using distributed FBG sensors ispresented. Strain modal analysis and parameter identification methods are introduced. Experimental strain modal testing and finite element analysis for a cantilever pipe have been carried out. The analysis results indicate that the natural frequencies and strain mode shapes of the tested pipe acquired by FBG sensors are in good agreement with the results obtained by a reference accelerometer and simulation outputs. The strain modal parameters of a hydraulic pipe were obtained by the proposed strain modal testing method. FBG sensors have been shown to be useful in the experimental strain modal analysis of small and light pipes in mechanical, aeronautic and aerospace applications. PMID- 27681729 TI - Electrocardiogram Signal Denoising Using Extreme-Point Symmetric Mode Decomposition and Nonlocal Means. AB - Electrocardiogram (ECG) signals contain a great deal of essential information which can be utilized by physicians for the diagnosis of heart diseases. Unfortunately, ECG signals are inevitably corrupted by noise which will severely affect the accuracy of cardiovascular disease diagnosis. Existing ECG signal denoising methods based on wavelet shrinkage, empirical mode decomposition and nonlocal means (NLM) cannot provide sufficient noise reduction or well-detailed preservation, especially with high noise corruption. To address this problem, we have proposed a hybrid ECG signal denoising scheme by combining extreme-point symmetric mode decomposition (ESMD) with NLM. In the proposed method, the noisy ECG signals will first be decomposed into several intrinsic mode functions (IMFs) and adaptive global mean using ESMD. Then, the first several IMFs will be filtered by the NLM method according to the frequency of IMFs while the QRS complex detected from these IMFs as the dominant feature of the ECG signal and the remaining IMFs will be left unprocessed. The denoised IMFs and unprocessed IMFs are combined to produce the final denoised ECG signals. Experiments on both simulated ECG signals and real ECG signals from the MIT-BIH database demonstrate that the proposed method can suppress noise in ECG signals effectively while preserving the details very well, and it outperforms several state-of-the-art ECG signal denoising methods in terms of signal-to-noise ratio (SNR), root mean squared error (RMSE), percent root mean square difference (PRD) and mean opinion score (MOS) error index. PMID- 27681730 TI - A Novel Petri Nets-Based Modeling Method for the Interaction between the Sensor and the Geographic Environment in Emerging Sensor Networks. AB - The service of sensor device in Emerging Sensor Networks (ESNs) is the extension of traditional Web services. Through the sensor network, the service of sensor device can communicate directly with the entity in the geographic environment, and even impact the geographic entity directly. The interaction between the sensor device in ESNs and geographic environment is very complex, and the interaction modeling is a challenging problem. This paper proposed a novel Petri Nets-based modeling method for the interaction between the sensor device and the geographic environment. The feature of the sensor device service in ESNs is more easily affected by the geographic environment than the traditional Web service. Therefore, the response time, the fault-tolerant ability and the resource consumption become important factors in the performance of the whole sensor application system. Thus, this paper classified IoT services as Sensing services and Controlling services according to the interaction between IoT service and geographic entity, and classified GIS services as data services and processing services. Then, this paper designed and analyzed service algebra and Colored Petri Nets model to modeling the geo-feature, IoT service, GIS service and the interaction process between the sensor and the geographic enviroment. At last, the modeling process is discussed by examples. PMID- 27681731 TI - A Cluster-Based Dual-Adaptive Topology Control Approach in Wireless Sensor Networks. AB - Multi-Input Multi-Output (MIMO) can improve wireless network performance. Sensors are usually single-antenna devices due to the high hardware complexity and cost, so several sensors are used to form virtual MIMO array, which is a desirable approach to efficiently take advantage of MIMO gains. Also, in large Wireless Sensor Networks (WSNs), clustering can improve the network scalability, which is an effective topology control approach. The existing virtual MIMO-based clustering schemes do not either fully explore the benefits of MIMO or adaptively determine the clustering ranges. Also, clustering mechanism needs to be further improved to enhance the cluster structure life. In this paper, we propose an improved clustering scheme for virtual MIMO-based topology construction (ICV MIMO), which can determine adaptively not only the inter-cluster transmission modes but also the clustering ranges. Through the rational division of cluster head function and the optimization of cluster head selection criteria and information exchange process, the ICV-MIMO scheme effectively reduces the network energy consumption and improves the lifetime of the cluster structure when compared with the existing typical virtual MIMO-based scheme. Moreover, the message overhead and time complexity are still in the same order of magnitude. PMID- 27681732 TI - Real-Time Performance of Mechatronic PZT Module Using Active Vibration Feedback Control. AB - This paper proposes an innovative mechatronic piezo-actuated module to control vibrations in modern machine tools. Vibrations represent one of the main issues that seriously compromise the quality of the workpiece. The active vibration control (AVC) device is composed of a host part integrated with sensors and actuators synchronized by a regulator; it is able to make a self-assessment and adjust to alterations in the environment. In particular, an innovative smart actuator has been designed and developed to satisfy machining requirements during active vibration control. This study presents the mechatronic model based on the kinematic and dynamic analysis of the AVC device. To ensure a real time performance, a H2-LQG controller has been developed and validated by simulations involving a machine tool, PZT actuator and controller models. The Hardware in the Loop (HIL) architecture is adopted to control and attenuate the vibrations. A set of experimental tests has been performed to validate the AVC module on a commercial machine tool. The feasibility of the real time vibration damping is demonstrated and the simulation accuracy is evaluated. PMID- 27681734 TI - Design of a Piezoelectric Accelerometer with High Sensitivity and Low Transverse Effect. AB - In order to meet the requirements of cable fault detection, a new structure of piezoelectric accelerometer was designed and analyzed in detail. The structure was composed of a seismic mass, two sensitive beams, and two added beams. Then, simulations including the maximum stress, natural frequency, and output voltage were carried out. Moreover, comparisons with traditional structures of piezoelectric accelerometer were made. To verify which vibration mode is the dominant one on the acceleration and the space between the mass and glass, mode analysis and deflection analysis were carried out. Fabricated on an n-type single crystal silicon wafer, the sensor chips were wire-bonged to printed circuit boards (PCBs) and simply packaged for experiments. Finally, a vibration test was conducted. The results show that the proposed piezoelectric accelerometer has high sensitivity, low resonance frequency, and low transverse effect. PMID- 27681733 TI - Magnetic Particles Coupled to Disposable Screen Printed Transducers for Electrochemical Biosensing. AB - Ultrasensitive biosensing is currently a growing demand that has led to the development of numerous strategies for signal amplification. In this context, the unique properties of magnetic particles; both of nano- and micro-size dimensions; have proved to be promising materials to be coupled with disposable electrodes for the design of cost-effective electrochemical affinity biosensing platforms. This review addresses, through discussion of selected examples, the way that nano and micro-magnetic particles (MNPs and MMPs; respectively) have contributed significantly to the development of electrochemical affinity biosensors, including immuno-, DNA, aptamer and other affinity modes. Different aspects such as type of magnetic particles, assay formats, detection techniques, sensitivity, applicability and other relevant characteristics are discussed. Research opportunities and future development trends in this field are also considered. PMID- 27681735 TI - Effect of Nanoparticles on Modified Screen Printed Inhibition Superoxide Dismutase Electrodes for Aluminum. AB - A novel amperometric biosensor for the determination of Al(III) based on the inhibition of the enzyme superoxide dismutase has been developed. The oxidation signal of epinephrine substrate was affected by the presence of Al(III) ions leading to a decrease in its amperometric current. The immobilization of the enzyme was performed with glutaraldehyde on screen-printed carbon electrodes modifiedwith tetrathiofulvalene (TTF) and different types ofnanoparticles. Nanoparticles of gold, platinum, rhodium and palladium were deposited on screen printed carbon electrodes by means of two electrochemical procedures. Nanoparticles were characterized trough scanning electronic microscopy, X-rays fluorescence, and atomic force microscopy. Palladium nanoparticles showed lower atomic force microscopy parameters and higher slope of aluminum calibration curves and were selected to perform sensor validation. The developed biosensor has a detection limit of 2.0 +/- 0.2 MUM for Al(III), with a reproducibility of 7.9% (n = 5). Recovery of standard reference material spiked to buffer solution was 103.8% with a relative standard deviation of 4.8% (n = 5). Recovery of tap water spiked with the standard reference material was 100.5 with a relative standard deviation of 3.4% (n = 3). The study of interfering ions has also been carried out. PMID- 27681736 TI - Environmental Noise Annoyance and Mental Health in Adults: Findings from the Cross-Sectional German Health Update (GEDA) Study 2012. AB - The health implications of environmental noise, especially cardiovascular effects, have been studied intensively. Research on associations between noise and mental health, however, has shown contradictory results. The present study examined associations between individual levels of noise annoyance due to noise from various sources in the living environment and mental health of adults in Germany. It evaluated whether these associations persisted after adjusting for potential covariates. Data were obtained from the cross-sectional "German Health Update" study 2012 (GEDA 2012), a national health interview survey among adults in Germany conducted by the Robert Koch Institute (n = 19,294). Noise annoyance questions referred to overall noise and that from road traffic, neighbours, and air traffic. Mental health was measured with the five-item Mental Health Inventory. Bivariate analysis showed associations between high levels of noise annoyance and impaired mental health for all noise sources except air traffic. After adjusting for covariates (sociodemographic factors, chronic disease, and social support), both men and women who reported high overall noise annoyance showed more than doubled odds of impaired mental health compared to those who were not annoyed. The odds of impaired mental health in the highest noise annoyance category from road traffic and neighbours were also significantly increased. These findings indicate that high noise annoyance is associated with impaired mental health and that this association can vary with the source of environmental noise. Further research on covariates of this association is necessary. Particularly, longitudinal data are required to establish the direction of associations and to address questions of causality. PMID- 27681737 TI - Children's Exposure to Secondhand Smoke during Ramadan in Jakarta, Indonesia. AB - Secondhand smoke exposure (SHS) causes a disproportionate health burden for children, yet existing smoke-free laws are often poorly enforced. We monitored air quality while observing children and adult nonsmokers present in public venues during Ramadan, a period of Muslim religious observance marked by family and social gatherings, in Jakarta, Indonesia. A repeated-measures design was used to assess indoor air quality during and after Ramadan in 43 restaurants and in five smoke-free control venues. Fine particulate matter of 2.5 microns or less (PM2.5) was sampled. The average number of children and active smokers present in each venue was also observed. PM2.5 levels were significantly higher during Ramadan (mean 86.5 ug/m3) compared with post-Ramadan (mean 63.2 ug/m3) in smoking venues (p = 0.015). During Ramadan, there were more active smokers (p = 0.012) and children (p = 0.051) observed in venues where smoking occurred, compared with the same venues post-Ramadan. Poor enforcement of the smoke-free law in Jakarta has failed to protect children from SHS exposure in public venues during Ramadan. Collaboration between the government, NGOs (such as the Indonesian Cancer Foundation (YKI) and the Smoking Control Foundation (LM3)), religious leaders, and venue owners and managers must be developed to ensure that the comprehensive smoking bans apply to all venues, and that smoke-free laws are enforced. PMID- 27681739 TI - Botulinum Toxin A for Controlling Obesity. AB - Rapid growth of the overweight population and the number of obese individuals in recent decades suggests that current strategies based on diet, exercise, and pharmacological knowledge are not sufficient to address this epidemic. Obesity is the result of a high caloric intake and energy storage, not counterbalanced by an equally important energy expense. Botulinum toxin type A (BoNT-A) use is rapidly expanding to include treatment of a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, painful, and cosmetic disorders. Many studies evaluating the effect of BoNT-A in gastric antrum e/o fundus for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BoNT-A in laparatomized rats induced a significant reduction of food intake and body weight. These studies have been published yielding debated results. Differences in the selection of patients, the doses of BoNT-A, the method of administration of the toxin, and the instruments of evaluation of some parameters among these studies may be the cause. In this review, it will study the state-of-the-art use of BoNT-A in obesity basic science models and review the clinical evidence on the therapeutic applications of BoNT-A for obesity. PMID- 27681738 TI - The Role of Bioactive Dietary Components in Modulating miRNA Expression in Colorectal Cancer. AB - Colorectal cancer is the third most common cancer in the world and considered to be one of the most diet-related types of cancer. Extensive research has been conducted but still the link between diet and colorectal cancer is complex. Recent studies have highlight microRNAs (miRNAs) as key players in cancer-related pathways in the context of dietary modulation. MicroRNAs are involved in most biological processes related to tumor development and progression; therefore, it is of great interest to understand the underlying mechanisms by which dietary patterns and components influence the expression of these powerful molecules in colorectal cancer. In this review, we discuss relevant dietary patterns in terms of miRNAs modulation in colorectal cancer, as well as bioactive dietary components able to modify gene expression through changes in miRNA expression. Furthermore, we emphasize on protective components such as resveratrol, curcumin, quercetin, alpha-mangostin, omega-3 fatty acids, vitamin D and dietary fiber, with a focus on the molecular mechanisms in the context of prevention and even treatment. In addition, several bioactive dietary components that have the ability to re-sensitize treatment resistant cells are described. PMID- 27681741 TI - How to Start with a Clean Crop: Biopesticide Dips Reduce Populations of Bemisia tabaci (Hemiptera: Aleyrodidae) on Greenhouse Poinsettia Propagative Cuttings. AB - (1) Global movement of propagative plant material is a major pathway for introduction of Bemisia tabaci (Hemiptera: Aleyrodidae) into poinsettia greenhouses. Starting a poinsettia crop with high pest numbers disrupts otherwise successful biological control programs and widespread resistance of B. tabaci against pesticides is limiting growers' options to control this pest; (2) This study investigated the use of several biopesticides (mineral oil, insecticidal soap, Beauveria bassiana, Isaria fumosorosea, Steinernema feltiae) and combinations of these products as immersion treatments (cutting dips) to control B. tabaci on poinsettia cuttings. In addition, phytotoxicity risks of these treatments on poinsettia cuttings, and effects of treatment residues on mortality of commercial whitefly parasitoids (Eretmocerus eremicus and Encarsia formosa) were determined; (3) Mineral oil (0.1% v/v) and insecticidal soap (0.5%) + B. bassiana (1.25 g/L) were the most effective treatments; only 31% and 29%, respectively, of the treated B. tabaci survived on infested poinsettia cuttings and B. tabaci populations were lowest in these treatments after eight weeks. Phytotoxicity risks of these treatments were acceptable, and dip residues had little effect on survival of either parasitoid, and are considered highly compatible; (4) Use of poinsettia cutting dips will allow growers to knock-down B. tabaci populations to a point where they can be managed successfully thereafter with existing biocontrol strategies. PMID- 27681742 TI - Automated and Multiplexed Soft Lithography for the Production of Low-Density DNA Microarrays. AB - Microarrays are established research tools for genotyping, expression profiling, or molecular diagnostics in which DNA molecules are precisely addressed to the surface of a solid support. This study assesses the fabrication of low-density oligonucleotide arrays using an automated microcontact printing device, the InnoStamp 40((r)). This automate allows a multiplexed deposition of oligoprobes on a functionalized surface by the use of a MacroStamp(TM) bearing 64 individual pillars each mounted with 50 circular micropatterns (spots) of 160 um diameter at 320 um pitch. Reliability and reuse of the MacroStamp(TM) were shown to be fast and robust by a simple washing step in 96% ethanol. The low-density microarrays printed on either epoxysilane or dendrimer-functionalized slides (DendriSlides) showed excellent hybridization response with complementary sequences at unusual low probe and target concentrations, since the actual probe density immobilized by this technology was at least 10-fold lower than with the conventional mechanical spotting. In addition, we found a comparable hybridization response in terms of fluorescence intensity between spotted and printed oligoarrays with a 1 nM complementary target by using a 50-fold lower probe concentration to produce the oligoarrays by the microcontact printing method. Taken together, our results lend support to the potential development of this multiplexed microcontact printing technology employing soft lithography as an alternative, cost competitive tool for fabrication of low-density DNA microarrays. PMID- 27681740 TI - Polyamines as Snake Toxins and Their Probable Pharmacological Functions in Envenomation. AB - While decades of research have focused on snake venom proteins, far less attention has been paid to small organic venom constituents. Using mostly pooled samples, we surveyed 31 venoms (six elapid, six viperid, and 19 crotalid) for spermine, spermidine, putrescine, and cadaverine. Most venoms contained all four polyamines, although some in essentially trace quantities. Spermine is a potentially significant component of many viperid and crotalid venoms (<=0.16% by mass, or 7.9 umol/g); however, it is almost completely absent from elapid venoms assayed. All elapid venoms contained larger molar quantities of putrescine and cadaverine than spermine, but still at levels that are likely to be biologically insignificant. As with venom purines, polyamines impact numerous physiological targets in ways that are consistent with the objectives of prey envenomation, prey immobilization via hypotension and paralysis. Most venoms probably do not contain sufficient quantities of polyamines to induce systemic effects in prey; however, local effects seem probable. A review of the pharmacological literature suggests that spermine could contribute to prey hypotension and paralysis by interacting with N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptors, nicotinic and muscarinic acetylcholine receptors, gamma-Aminobutyric acid (GABA) receptors, blood platelets, ryanodine receptors, and Ca2+-ATPase. It also blocks many types of cation-permeable channels by interacting with negatively charged amino acid residues in the channel mouths. The site of envenomation probably determines which physiological targets assume the greatest importance; however, venom-induced liberation of endogenous, intracellular stores of polyamines could potentially have systemic implications and may contribute significantly to envenomation sequelae. PMID- 27681744 TI - Improving Head and Neck Cancer Outcomes: Technology, Used Wisely. PMID- 27681743 TI - The Clinical Diagnosis and Management of Kawasaki Disease: a Review and Update. AB - Kawasaki disease is an acute, self-limited vasculitis of childhood and has become the leading cause of acquired pediatric heart disease in the USA. Prompt treatment is essential in reducing cardiac-related morbidity and mortality. The underlying etiology remains unknown. The disease itself may be the characteristic manifestation of a common pathway of immune-mediated vascular inflammation in susceptible hosts. The characteristic clinical features of fever for at least 5 days with bilateral nonpurulent conjunctivitis, rash, changes in lips and oral cavity, changes in peripheral extremities, and cervical lymphadenopathy remain the mainstay of diagnosis. Supplementary laboratory criteria can aid in the diagnosis, particularly in cases of incomplete clinical presentation. Diagnosis of Kawasaki disease can be challenging as the clinical presentation can be mistaken for a variety of other pediatric illnesses. Standard of care consists of intravenous immune globulin and aspirin. Corticosteroids, infliximab, and cyclosporine A have been used as adjunct therapy for Kawasaki disease refractory to initial treatment. There is ongoing research into the use of these agents in the initial therapy of Kawasaki disease. PMID- 27681745 TI - The Radiation Oncology Job Market: The Economics and Policy of Workforce Regulation. AB - Examinations of the US radiation oncology workforce offer inconsistent conclusions, but recent data raise significant concerns about an oversupply of physicians. Despite these concerns, residency slots continue to expand at an unprecedented pace. Employed radiation oncologists and professional corporations with weak contracts or loose ties to hospital administrators would be expected to suffer the greatest harm from an oversupply. The reduced cost of labor, however, would be expected to increase profitability for equipment owners, technology vendors, and entrenched professional groups. Policymakers must recognize that the number of practicing radiation oncologists is a poor surrogate for clinical capacity. There is likely to be significant opportunity to augment capacity without increasing the number of radiation oncologists by improving clinic efficiency and offering targeted incentives for geographic redistribution. Payment policy changes significantly threaten radiation oncologists' income, which may encourage physicians to care for greater patient loads, thereby obviating more personnel. Furthermore, the implementation of alternative payment models such as Medicare's Oncology Care Model threatens to decrease both the utilization and price of radiation therapy by turning referring providers into cost-conscious consumers. Medicare funds the vast majority of graduate medical education, but the extent to which the expansion in radiation oncology residency slots has been externally funded is unclear. Excess physician capacity carries a significant risk of harm to society by suboptimally allocating intellectual resources and creating comparative shortages in other, more needed disciplines. There are practical concerns associated with a market-based solution in which medical students self-regulate according to job availability, but antitrust law would likely forbid collaborative self-regulation that purports to restrict supply. Because Congress is unlikely to create one central body to govern residency controls for all specialties, we recommend better reporting of program specific employment metrics and careful, intellectually honest re-evaluation of existing Accreditation Council for Graduate Medical Education accreditation standards. PMID- 27681746 TI - Masters of Our Destiny: From Jazz Quartet to Symphony Orchestra. PMID- 27681747 TI - Applicant Interview Experiences and Postinterview Communication of the 2016 Radiation Oncology Match Cycle. AB - PURPOSE: To characterize applicant interview experiences at radiation oncology residency programs during the 2016 match cycle and to assess applicant opinions regarding postinterview communication (PIC) after recent attention to gamesmanship noted in prior match cycles. METHODS AND MATERIALS: An anonymous, institutional review board-approved, 29-question survey was deployed following the rank order list deadline to all 2016 radiation oncology residency applicants applying to a single institution. RESULTS: Complete surveys were returned by 118 of 210 applicants, for a 56% response rate. Regarding possible match violation questions, 84% of respondents were asked at least once about where else they were interviewing (occurred at a median of 20% of program interviews); 51% were asked about marital status (6% of interviews); and 22% were asked about plans to have children (1% of interviews). Eighty-three percent of applicants wrote thank-you notes, with 55% reporting fear of being viewed unfavorably if such notes were not communicated. Sixty percent of applicants informed a program that they had ranked a program highly; 53% felt this PIC strategy would improve their standing on the rank order list, yet 46% reported feeling distressed by this obligation. A majority of applicants stated that they would feel relieved if programs explicitly discouraged PIC (89%) and that it would be preferable if programs prohibited applicants from notifying the program of their rank position (66%). CONCLUSIONS: Potential match violations occur at a high rate but are experienced at a minority of interviews. Postinterview communication occurs frequently, with applicants reporting resultant distress. Respondents stated that active discouragement of both thank-you notes/e-mails and applicants' notification to programs of their ranking would be preferred. PMID- 27681748 TI - Radiation Oncology and Online Patient Education Materials: Deviating From NIH and AMA Recommendations. AB - PURPOSE: Physicians encourage patients to be informed about their health care options, but much of the online health care-related resources can be beneficial only if patients are capable of comprehending it. This study's aim was to assess the readability level of online patient education resources for radiation oncology to conclude whether they meet the general public's health literacy needs as determined by the guidelines of the United States National Institutes of Health (NIH) and the American Medical Association (AMA). METHODS: Radiation oncology-related internet-based patient education materials were downloaded from 5 major professional websites (American Society for Radiation Oncology, American Association of Physicists in Medicine, American Brachytherapy Society, RadiologyInfo.org, and Radiation Therapy Oncology Group). Additional patient education documents were downloaded by searching for key radiation oncology phrases using Google. A total of 135 articles were downloaded and assessed for their readability level using 10 quantitative readability scales that are widely accepted in the medical literature. RESULTS: When all 10 assessment tools for readability were taken into account, the 135 online patient education articles were written at an average grade level of 13.7 +/- 2.0. One hundred nine of the 135 articles (80.7%) required a high school graduate's comprehension level (12th grade level or higher). Only 1 of the 135 articles (0.74%) met the AMA and NIH recommendations for patient education resources to be written between the third grade and seventh-grade levels. CONCLUSION: Radiation oncology websites have patient education material written at an educational level above the NIH and AMA recommendations; as a result, average American patients may not be able to fully understand them. Rewriting radiation oncology patient education resources would likely contribute to the patients' understanding of their health and treatment options, making each physician-patient interaction more productive and efficient. PMID- 27681750 TI - Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland. AB - PURPOSE: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology. However, the regulatory events of NAMPT in response to the irradiated salivary gland are unknown. METHODS AND MATERIALS: The cell viability of primary cultured submandibular gland cells was determined using the PrestoBlue assay. NAMPT expression was measured using reverse transcriptase polymerase chain reaction and Western blotting in vitro and in vivo. Silent information regulator 1 (SIRT1) and phosphorylated Akt protein levels were examined by Western blotting. The cellular locations of NAMPT and SIRT1 were detected by immunohistochemistry. NAMPT promoter activity was assessed using the luciferase reporter gene assay. RESULTS: NAMPT was mainly distributed in the cytoplasm of granular convoluted tubule cells and ductal cells in normal submandibular glands. mRNA and protein expression of NAMPT was downregulated after radiation but upregulated with phenylephrine pretreatment both in vivo and in vitro. Moreover, the protein expression of phosphorylated Akt and SIRT1 was decreased in irradiated glands, and phenylephrine pretreatment restored the expression of both. SIRT1 was mainly located in the cell nucleus and cytoplasm in the normal submandibular gland. Phenylephrine dramatically enhanced the expression of SIRT1, which was significantly reduced by radiation. Furthermore, phenylephrine induced a marked increase of NAMPT promoter activity. CONCLUSIONS: These findings reveal the regulatory mechanisms of NAMPT expression, which help to understand the mechanism of the cytoprotective role of phenylephrine on irradiated tissues. PMID- 27681749 TI - Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer. AB - PURPOSE: To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. METHODS AND MATERIALS: A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. RESULTS: The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. CONCLUSIONS: It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics. PMID- 27681751 TI - Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy. AB - PURPOSE: To examine the effect of radiation on in vitro drug activation and release of Promitil, a pegylated liposomal formulation of a mitomycin C (MMC) lipid-based prodrug; and examine the efficacy and toxicity of Promitil with concurrent radiation in colorectal cancer models. METHODS AND MATERIALS: Promitil was obtained from Lipomedix Pharmaceuticals (Jerusalem, Israel). We tested the effects of radiation on release of active MMC from Promitil in vitro. We next examined the radiosensitization effect of Promitil in vitro. We further evaluated the toxicity of a single injection of free MMC or Promitil when combined with radiation by assessing the effects on blood counts and in-field skin and hair toxicity. Finally, we compared the efficacy of MMC and Promitil in chemoradiotherapy using mouse xenograft models. RESULTS: Mitomycin C was activated and released from Promitil in a controlled-release profile, and the rate of release was significantly increased in medium from previously irradiated cells. Both Promitil and MMC potently radiosensitized HT-29 cells in vitro. Toxicity of MMC (8.4 mg/kg) was substantially greater than with equivalent doses of Promitil (30 mg/kg). Mice treated with human-equivalent doses of MMC (3.3 mg/kg) experienced comparable levels of toxicity as Promitil-treated mice at 30 mg/kg. Promitil improved the antitumor efficacy of 5-fluorouracil-based chemoradiotherapy in mouse xenograft models of colorectal cancer, while equitoxic doses of MMC did not. CONCLUSIONS: We demonstrated that Promitil is an attractive agent for chemoradiotherapy because it demonstrates a radiation-triggered release of active drug. We further demonstrated that Promitil is a well-tolerated and potent radiosensitizer at doses not achievable with free MMC. These results support clinical investigations using Promitil in chemoradiotherapy. PMID- 27681752 TI - The Involvement of Mitochondrial Membrane Potential in Cross-Resistance Between Radiation and Docetaxel. AB - PURPOSE: To understand the molecular mechanisms underlying cancer cell radioresistance, clinically relevant radioresistant (CRR) cells that continue to proliferate during exposure to 2 Gy/day X-rays for more than 30 days were established. A modified high-density survival assay for anticancer drug screening revealed that CRR cells were resistant to an antimicrotubule agent, docetaxel (DTX). The involvement of reactive oxygen species (ROS) from mitochondria (mtROS) in the cross-resistance to X-rays and DTX was studied. METHODS AND MATERIALS: Sensitivity to anticancer agents was determined by a modified high-density cell survival or water-soluble tetrazolium salt assay. DTX-induced mtROS generation was determined by MitoSOX red staining. JC-1 staining was used to visualize mitochondrial membrane potential. DTX-induced DNA double-strand breaks were determined by gamma-H2AX staining. To obtain mitochondrial DNA-lacking (rho(0)) cells, the cells were cultured for 3 to 4 weeks in medium containing ethidium bromide. RESULTS: Treatment with DTX increased mtROS in parental cells but not in CRR cells. DTX induced DNA double-strand breaks in parental cells. The mitochondrial membrane potential of CRR cells was lower in CRR cells than in parental cells. Depletion of mtDNA induced DTX resistance in parental cells. Treatment with dimethyl sulfoxide also induced DTX resistance in parental cells. CONCLUSIONS: The mitochondrial dysfunction observed in CRR cells contributes to X ray and DTX cross-resistance. The activation of oxidative phosphorylation in CRR cells may represent an effective approach to overcome radioresistant cancers. In general, the overexpression of beta-tubulin or multidrug efflux pumps is thought to be involved in DTX resistance. In the present study, we discovered another DTX resistant mechanism by investigating CRR cells. PMID- 27681753 TI - A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma. AB - PURPOSE: Local radiation therapy (RT) combined with systemic anti-cytotoxic T lymphocyte-associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. METHODS AND MATERIALS: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had >=1 nonirradiated metastasis measuring >=1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. RESULTS: Combination therapy was well tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32 65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8 activated T-cells and response. CONCLUSION: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT. PMID- 27681754 TI - Stroke After Radiation Therapy for Head and Neck Cancer: What Is the Risk? AB - PURPOSE: A retrospective population-based cohort study was conducted to determine the risk of ischemic stroke with respect to time, associated with curative radiation therapy in head and neck squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: On the basis of data from the Ontario Cancer Registry and regional cancer treatment centers, 14,069 patients were identified with diagnoses of squamous cell carcinoma of the oral cavity, larynx, and pharynx who were treated for cure between 1990 and 2010. Hazards of stroke and time to stroke were examined, accounting for the competing risk of death. Stroke risk factors identified through diagnostic and procedural administrative codes were adjusted for in the comparison between treatment regimens, which included surgery alone versus radiation therapy alone and surgery alone versus any exposure to radiation therapy. RESULTS: Overall, 6% of patients experienced an ischemic stroke after treatment, with 5% experiencing a stroke after surgery, 8% after radiation therapy alone, and 6% after any exposure to radiation therapy. The cause-specific hazard ratios of ischemic stroke after radiation therapy alone and after any exposure to radiation therapy compared with surgery were 1.70 (95% confidence interval [CI]: 1.41-2.05) and 1.46 (95% CI: 1.23-1.73), respectively, after adjustment for stroke risk factors, patient factors, and disease-related factors. CONCLUSIONS: Radiation therapy was associated with an increased risk of ischemic stroke compared with surgery alone: for both radiation therapy alone and after all treatment modalities that included any radiation treatment were combined. Because of a shift toward a younger HNSCC patient population, our results speak to the need for adequate follow-up and survivorship care among patients who have been treated with radiation therapy. Advances in treatment that minimize chronic morbidity also require further evaluation. PMID- 27681756 TI - Adjuvant Chemotherapy Is More Suitable Than Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer Patients Treated With Radical Chemoradiotherapy. PMID- 27681755 TI - Simultaneous Integrated Boost Volumetric Modulated Arc Therapy in the Postoperative Treatment of High-Risk to Intermediate-Risk Endometrial Cancer: Results of ADA II Phase 1-2 Trial. AB - PURPOSE: A prospective phase 1-2 clinical trial aimed at determining the recommended postoperative dose of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) in a large series of patients with high-risk and intermediate-risk endometrial cancer (HIR-EC) is presented. The study also evaluated the association between rate and severity of toxicity and comorbidities and the clinical outcomes. METHODS AND MATERIALS: Two SIB-VMAT dose levels were investigated for boost to the vaginal vault, whereas the pelvic lymph nodes were always treated with 45 Gy. The first cohort received a SIB-VMAT dose of 55 Gy in 25 consecutive 2.2-Gy fractions, and the subsequent cohort received higher doses (60 Gy in 2.4-Gy fractions). RESULTS: Seventy consecutive HIR-EC patients, roughly half of whom were obese (47.1%) or overweight (37.1%), with Charlson Age Comorbidity Index >2 (48.5%), were enrolled. Thirty-one patients (44.3%) were administered adjuvant chemotherapy before starting radiation therapy. All patients (n=35 per dose level) completed irradiation without any dose-limiting toxicity. Proctitis (any grade) was associated with radiation therapy dose (P=.001); not so enterocolitis. Grade >=2 gastrointestinal (GI) and genitourinary (GU) toxicity were recorded in 17 (24.3%) and 14 patients (20.0%), respectively, and were not associated with radiation dose. As for late toxicity, none of patients experienced late grade >=3 GI or grade >=2 GU toxicity. The 3-year late grade >=2 GI and GU toxicity-free survival were 92.8% and 100%, respectively, with no difference between the 2 dose levels. With a median follow-up period of 25 months (range, 4-60 months), relapse/progression of disease was observed in 10 of 70 patients (14.2%). The 3-year cumulative incidence of recurrence was 1.5% (95% confidence interval (CI): 0.2-10.7), whereas the 3-year disease-free survival was 81.3% (95% CI: 65.0-90.0). CONCLUSIONS: This clinical study showed the feasibility of this technique and its good profile in terms of acute and late toxicity at the recommended doses even in aged and frail patients. PMID- 27681758 TI - Prostate Brachytherapy Case Volumes by Academic and Nonacademic Practices: Implications for Future Residency Training. AB - PURPOSE: The use of prostate brachytherapy has continued to decline in the United States. We examined the national practice patterns of both academic and nonacademic practices performing prostate brachytherapy by case volume per year to further characterize the decline and postulate the effect this trend might have on training the next generation of residents. METHODS AND MATERIALS: Men diagnosed with prostate cancer who had undergone radiation therapy in 2004 to 2012 were identified. The annual brachytherapy case volume at each facility was determined and further categorized into <=12 cases per year (ie, an average of <=1 cases per month), 13 to 52 cases per year, and >=53 cases per year (ie, an average of >=1 cases per week) in academic practices versus nonacademic practices. RESULTS: In 2004 to 2012, academic practices performing an average of <=1 brachytherapy cases per month increased from 56.4% to 73.7%. In nonacademic practices, this percentage increased from 60.2% to 77.4% (P<.0001 for both). Practices performing an average of >=1 cases per week decreased among both academic practices (from 6.7% to 1.5%) and nonacademic practices (from 4.5% to 2.7%). CONCLUSIONS: Both academic and nonacademic radiation oncology practices have demonstrated a significant reduction in the use of prostate brachytherapy from 2004 to 2012. With the case volume continuing to decline, it is unclear whether we are prepared to train the next generation of residents in this critical modality. PMID- 27681759 TI - The Henri Mondor Procedure of Morbidity and Mortality Review Meetings: Prospective Registration of Clinical, Dosimetric, and Individual Radiosensitivity Data of Patients With Severe Radiation Toxicity. AB - PURPOSE: After radiation therapy (RT), various radiation-induced toxicities can develop in about one-fourth of patients. An international interest in using morbidity and mortality rates to monitor the quality of care and integrate morbidity and mortality review (MMR) meetings into organizations' governance processes has arisen. We report the first results of patients included in our MMR procedure that included biological assays for individual intrinsic radiosensitivity (IIRS). METHODS AND MATERIALS: Twenty-three patients were prospectively included in the MMR database. Twenty-two were evaluable for IIRS. Prostate (n=10) and breast (n=8) cancers were the most frequent disease types. The total dose delivered, determined according to the type of disease, ranged from 30 to 74 Gy. Our MMR procedure requires strict criteria: patients with unresolved toxicity of grade 3 or higher with availability of clinical (photographic) data, IIRS results obtained from skin biopsy assays, treatment modalities, and follow-up data. The RT technique and dosimetry were reviewed. RESULTS: Our prospective registration of toxicities showed mainly rectitis, occurring in 7 cases, and skin toxicities, occurring in 9. Of the 7 patients with rectitis, 5 received 66 Gy of post-prostatectomy RT with V50 (rectum volume receiving 50 Gy) ranging from 45% to 75% and a mean maximal dose of 66.5 Gy. For dermatitis and cystitis, the mean maximal doses were in the range of classical constraints without any overdosage or dose heterogeneity. No errors were found in the review of treatment planning and positioning. Conversely, all the patients were considered biologically as radiosensitive with genomic instability and ATM (ataxia telangiectasia mutated)-dependent DNA double-strand break repair impairments. CONCLUSIONS: The MMR review of files allowed clear answers for patients on the relationship between clinical events and their IIRS. Our procedure has allowed education of all our staff to monitor, identify, and document clinical, physical, and biological aspects of radiation-induced toxicities. Thus we recommend the introduction of the MMR procedure in RT departments. PMID- 27681757 TI - Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis-Free Survival and Prostate Cancer-Specific Mortality. AB - OBJECTIVES/BACKGROUND: To determine whether a 6-month posttreatment prostate specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). METHODS: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, and cumulative incidence was used to estimate PCSM. RESULTS: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA <=0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6 month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. CONCLUSIONS: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early salvage therapy on future clinical trials. PMID- 27681760 TI - Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy. AB - PURPOSE: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). METHODS AND MATERIALS: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. RESULTS: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10 year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with >=3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, >=3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). CONCLUSIONS: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with >=3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT. PMID- 27681761 TI - Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination. AB - PURPOSE: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. METHODS AND MATERIALS: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV56) were evaluated to identify the predictors for NTCP improvement. RESULTS: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV56 >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV56 >22% predicted benefit with C70 (P<.01). CONCLUSIONS: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the percentage of overlap of the PTV with organs at risk can predict which patients will benefit and inform future clinical trial design. PMID- 27681762 TI - Head and Neck Margin Reduction With Adaptive Radiation Therapy: Robustness of Treatment Plans Against Anatomy Changes. AB - PURPOSE: We set out to investigate loss of target coverage from anatomy changes in head and neck cancer patients as a function of applied safety margins and to verify a cone beam computed tomography (CBCT)-based adaptive strategy with an average patient anatomy to overcome possible target underdosage. METHODS AND MATERIALS: For 19 oropharyngeal cancer patients, volumetric modulated arc therapy treatment plans (2 arcs; simultaneous integrated boost, 70 and 54.25 Gy; 35 fractions) were automatically optimized with uniform clinical target volume (CTV) to-planning target volume margins of 5, 3, and 0 mm. We applied b-spline CBCT-to computed tomography (CT) deformable registration to allow recalculation of the dose on modified CT scans (planning CT deformed to daily CBCT following online positioning) and dose accumulation in the planning CT scan. Patients with deviations in primary or elective CTV coverage >2 Gy were identified as candidates for adaptive replanning. For these patients, a single adaptive intervention was simulated with an average anatomy from the first 10 fractions. RESULTS: Margin reduction from 5 mm to 3 mm to 0 mm generally led to an organ-at risk (OAR) mean dose (Dmean) sparing of approximately 1 Gy/mm. CTV shrinkage was mainly seen in the elective volumes (up to 10%), likely related to weight loss. Despite online repositioning, substantial systematic errors were present (>3 mm) in lymph node CTV, the parotid glands, and the larynx. Nevertheless, the average increase in OAR dose was small: maximum of 1.2 Gy (parotid glands, Dmean) for all applied margins. Loss of CTV coverage >2 Gy was found in 1, 3, and 7 of 73 CTVs, respectively. Adaptive intervention in 0-mm plans substantially improved coverage: in 5 of 7 CTVs (in 6 patients) to <2 Gy of initially planned. CONCLUSIONS: Volumetric modulated arc therapy head and neck cancer treatment plans with 5-mm margins are robust for anatomy changes and show a modest increase in OAR dose. Margin reduction improves OAR sparing with approximately 1 Gy/mm at the expense of target coverage in a subgroup of patients. Patients at risk of CTV underdosage >2 Gy in 0-mm plans may be identified early in treatment using dose accumulation. A single intervention with an average anatomy derived from CBCT effectively mitigates discrepancies. PMID- 27681763 TI - Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer. AB - PURPOSE: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with +/-3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with +/-3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. RESULTS: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. CONCLUSIONS: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. PMID- 27681764 TI - (18)F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy. AB - PURPOSE: We sought to investigate the ability of mid-treatment (18)F fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. METHODS AND MATERIALS: This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized (18)F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We used nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3 fold analyses. RESULTS: Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion. Symptom progression was predicted with an AUC of 0.75. Dose metrics performed poorly at classifying esophagitis (AUC of 0.52, grade 2 or higher mid treatment) or predicting symptom progression (AUC of 0.67). CONCLUSIONS: Normalized uptake can objectively, locally, and noninvasively quantify esophagitis during radiation therapy and predict eventual symptoms from asymptomatic patients. Normalized uptake may provide patient-specific dose response information not discernible from dose. PMID- 27681768 TI - In Regard to Vaidya et al. PMID- 27681767 TI - Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging. AB - PURPOSE: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)-induced damage to whole-brain WM bundles. METHODS AND MATERIALS: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Six DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. RESULTS: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. CONCLUSIONS: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT. PMID- 27681765 TI - Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography. AB - PURPOSE: To develop an imaging method to characterize and map marrow composition in the entire skeletal system, and to simulate differential targeted marrow irradiation based on marrow composition. METHODS AND MATERIALS: Whole-body dual energy computed tomography (DECT) images of cadavers and leukemia patients were acquired, segmented to separate bone marrow components, namely, bone, red marrow (RM), and yellow marrow (YM). DECT-derived marrow fat fraction was validated using histology of lumbar vertebrae obtained from cadavers. The fractions of RM (RMF = RM/total marrow) and YMF were calculated in each skeletal region to assess the correlation of marrow composition with sites and ages. Treatment planning was simulated to target irradiation differentially at a higher dose (18 Gy) to either RM or YM and a lower dose (12 Gy) to the rest of the skeleton. RESULTS: A significant correlation between fat fractions obtained from DECT and cadaver histology samples was observed (r=0.861, P<.0001, Pearson). The RMF decreased in the head, neck, and chest was significantly inversely correlated with age but did not show any significant age-related changes in the abdomen and pelvis regions. Conformity of radiation to targets (RM, YM) was significantly dependent on skeletal sites. The radiation exposure was significantly reduced (P<.05, t test) to organs at risk (OARs) in RM and YM irradiation compared with standard total marrow irradiation (TMI). CONCLUSIONS: Whole-body DECT offers a new imaging technique to visualize and measure skeletal-wide marrow composition. The DECT based treatment planning offers volumetric and site-specific precise radiation dosimetry of RM and YM, which varies with aging. Our proposed method could be used as a functional compartment of TMI for further targeted radiation to specific bone marrow environment, dose escalation, reduction of doses to OARs, or a combination of these factors. PMID- 27681766 TI - Fast Megavoltage Computed Tomography: A Rapid Imaging Method for Total Body or Marrow Irradiation in Helical Tomotherapy. AB - PURPOSE: Megavoltage computed tomographic (MVCT) imaging has been widely used for the 3-dimensional (3-D) setup of patients treated with helical tomotherapy (HT). One drawback of MVCT is its very long imaging time, the result of slow couch speeds of approximately 1 mm/s, which can be difficult for the patient to tolerate. We sought to develop an MVCT imaging method allowing faster couch speeds and to assess its accuracy for image guidance for HT. METHODS AND MATERIALS: Three cadavers were scanned 4 times with couch speeds of 1, 2, 3, and 4 mm/s. The resulting MVCT images were reconstructed using an iterative reconstruction (IR) algorithm with a penalty term of total variation and with a conventional filtered back projection (FBP) algorithm. The MVCT images were registered with kilovoltage CT images, and the registration errors from the 2 reconstruction algorithms were compared. This fast MVCT imaging was tested in 3 cases of total marrow irradiation as a clinical trial. RESULTS: The 3-D registration errors of the MVCT images reconstructed with the IR algorithm were smaller than the errors of images reconstructed with the FBP algorithm at fast couch speeds (2, 3, 4 mm/s). The scan time and imaging dose at a speed of 4 mm/s were reduced to 30% of those from a conventional coarse mode scan. For the patient imaging, faster MVCT (3 mm/s couch speed) scanning reduced the imaging time and still generated images useful for anatomic registration. CONCLUSIONS: Fast MVCT with the IR algorithm is clinically feasible for large 3-D target localization, which may reduce the overall time for the treatment procedure. This technique may also be useful for calculating daily dose distributions or organ motion analyses in HT treatment over a wide area. Automated integration of this imaging is at least needed to further assess its clinical benefits. PMID- 27681769 TI - In Reply to Park et al. PMID- 27681770 TI - In Regard to Takiar et al. PMID- 27681771 TI - In Regard to Boda-Heggemann et al. PMID- 27681772 TI - In Reply to Mansha. PMID- 27681773 TI - Micellar HPLC Method for Simultaneous Determination of Ethamsylate and Mefenamic Acid in Presence of Their Main Impurities and Degradation Products. AB - An eco-friendly sensitive, rapid and less hazardous micellar liquid chromatographic method was developed and validated for the simultaneous analysis of ethamsylate (ETM) and mefenamic acid (MFA) in the presence of hydroquinone (HQ) and 2,3-dimethylaniline (DMA) the main impurities of ETM and MFA, respectively. Good chromatographic separation was attained using Eclipse XDB-C8 column (150 mm * 4.6 mm, 5 MUm particle size) adopting UV detection at 300 nm with micellar mobile phase consisting of 0.12 M sodium dodecyl sulfate, 0.3% triethylamine and 15% 2-propanol in 0.02 M orthophosphoric acid (pH 7.0) at 1.0 mL/min. The analytes were well resolved in <6.0 min, ETM (tR = 1.55 min), HQ (tR = 1.95 min), MFA (tR = 4.55 min) and DMA (tR = 5.80 min). Different validation parameters were examined as recommended by international conference on harmonization (ICH) guidelines. The method was linear over the concentration ranges of 0.5-18.0, 0.5-20.0, 0.01-0.5 and 0.02-0.2 ug/mL with limits of detection of 0.118, 0.159, 0.005 and 0.005 ug/mL and limits of quantification of 0.358, 0.482, 0.014 and 0.015 ug/mL for ETM, MFA, HQ and DMA, respectively. The suggested method was successfully applied for the determination of the two drugs in their bulk powder, laboratory-prepared mixtures, single-ingredient and co formulated tablets. The obtained results were in accordance with those of the comparison method. The method can also detect trace amounts of HQ and DMA as the main impurities of ETM and MFA, respectively, within the BP limit (0.1%) for both impurities. Furthermore, it is a stability-indicating one for the determination of ETM in its pure form, single-component tablet and co-formulated tablets with other drugs. PMID- 27681774 TI - Development and Validation of Chiral HPLC Method for Quantification of 3-(S) Quinuclidinol in Pharmaceutically Important Precursor, 3-(R)-Quinuclidinol, by Precolumn Derivatization. AB - A sensitive and specific high-performance liquid chromatography (HPLC) method for the separation and quantification of 3-(S)-quinuclidinol in 3-(R)-quinuclidinol, precursor for active pharmaceutical ingredients (solifenacin, revatropate and talsaclidine), has been developed and validated by precolumn derivatization. Several chiral columns were tested in a normal phase system. Excellent enantioseparation with the resolution more than 11.4 was achieved on Chiralpak IC column using isocratic mobile phase consisting of n-hexane, ethanol, 2-propanol and diethylamine (80:8:12:0.4, v/v). The detection was carried out using UV detector at 230 nm. The influence of mobile phase composition, namely organic modifiers, additives, aliphatic alkanes and water content in mobile phase, on retention and enantioseparation was studied. Validation of the developed method including specificity, system suitability, limit of detection, limit of quantification, linearity, repeatability, intermediate precision, accuracy and solution stability was performed according to the International Conference on Harmonization guidelines. The advantage of the method is a good HPLC enantioseparation by precolumn derivatization using reaction mixture as sample, simpler UV detection, short analysis time (<30 min), and therefore this method is suitable option for routine quantification of 3-(S)-quinuclidinol in 3-(R) quinuclidinol. PMID- 27681775 TI - Separation of Isomers of JWH-122 on Porous Graphitic Carbon Stationary Phase with Non-Aqueous Mobile Phase Using Intelligent Software. AB - Cannabimimetic compounds have gained an increasing attention from the forensic community during the past few years. The present study was aimed to develop a liquid chromatographic separation method for the analysis of JWH-122 and its methyl isomers. In Hungary, JWH-122 is scheduled as a narcotic compound and its methyl isomers fall into the new psychoactive substance category, attracting significantly milder punishment than JWH-122 does. According to our best knowledge, gas chromatography or reversed phase liquid chromatography coupled with mass spectrometry could not be applied for separation and selective determination of methyl-naphthoyl indol isomers. In this study, we aimed to develop a high performance liquid chromatography method with UV and mass spectrometric detection for the separation of JWH-122 and all its possible isomers, depending on the position of methyl group on the naphthyl frame. Different reversed phase columns were used. Alkyl-modified silica with different selectivity and morphology with different mobile phase composition cannot be applied for separation of JWH-122 isomers. Porous graphitic carbon (PGC) column was used for separation of banned JWH-122 and each of its methyl isomers. In method development, a Quality by Design approach is presented for modeling the retention of the compounds. According to our knowledge, this is the first time reporting the use of intelligent software to estimate the retention on PGC material and using non-aqueous conditions. Retention times predicted by two program packages (STATISTICA(r) and DryLab(r)) are compared. The possibilities and limitations of the software modeling in the conditions described above are also evaluated. PMID- 27681776 TI - Quantitative In Silico Analysis of Retention of Nitrobenzofurazan-Amino Acids in Reversed-Phase Ion-Pair Liquid Chromatography. AB - The retention mechanisms of nitrobenzofurazan (NBD)-amino acids in reversed-phase ion-pair liquid chromatography were quantitatively analyzed in silico The most contributed interaction for the retention is the Lewis acid-base interaction between an aromatic ring of NBD-amino acids and hydroxyl-group hydrogen of tetra butyl-ammonium hydroxide coated on the hydrophobic phase. Solvent effects significantly improved the relation between the calculated molecular interaction (MI) energy values using a molecular mechanics program and log k values measured in chromatography. The correlation coefficient between the calculated MI energy values and the log k values was >0.95. PMID- 27681777 TI - [Endometriosis : An often unrecognized pain disorder]. AB - Endometriosis is a chronic disease of women during their reproductive age. The most typical symptoms are dysmenorrhoea, dyspareunia, dysuria, cyclical and acyclical pelvic pain, bleeding disorders and infertility. These symptoms lead to significant impairment of the quality of life and economic burden. The prevalence is estimated to be 2-20 % of all women in this age and due to this fact, it is one of the most frequently benign gynecological diseases. Not all women suffer from severe symptoms, but more than 50 % require ongoing treatment. Beside the severe physical impairment due to the pain, the high recurrence rate of 50-80 % also after surgical and/or hormonal treatment is problematic. The interval between onset of symptoms and diagnosis is approximately 6-8 years. These problems are a consequence of lack of knowledge about the pathogenesis of the disease and the pain mechanisms as well as the lack of awareness of physicians in this field. PMID- 27681778 TI - [Impact of attachment behavior on chronic and somatoform pain]. AB - In addition to being a risk factor for the course of chronic pain, the personality characteristics of the individual attachment style are also predictors for the success of medical and psychosocial interventions and aspects of the physician-patient relationship. Insecurely attached patients seem to be less able to sustain the positive effects of pain therapy. These results are especially relevant as insecure attachment patterns are overrepresented among chronic pain patients. As a result the attachment style can be seen as a psychosocial vulnerability factor for the chronification of acute pain. PMID- 27681780 TI - ? PMID- 27681779 TI - [Effect of oxytocin on human pain perception]. AB - BACKGROUND: Over the years the effect of the neuropeptide oxytocin and its possible utilization for pain management has been increasingly more investigated and discussed. Initial results emphasized the effects of oxytocin with respect to labor and breastfeeding. Diverse animals studies were also able to demonstrate the effectiveness of the peptide in attachment behavior and pain perception; however, it is still unclear how oxytocin affects pain perception in humans. The potential therapeutic effectiveness of oxytocin could be particularly important for primary and secondary treatment of pain patients because chronification of pain can occur more frequently in this area. METHODS: For this review the databases PubMed, Medline und PsycINFO were searched using the terms oxytocin, pain, human and analgesic. The search resulted in a total of 89 original articles after excluding articles regarding labor pain, breastfeeding and animal studies. Only those studies were included which were carried out between 1994 and 2015. A total of 17 articles remained for inclusion in this review and included 13 studies on the exogenous application of oxytocin and 4 on measurement of oxytocin levels in plasma. CONCLUSION: This review article gives a summary of the current state of research on oxytocin and its direct and indirect association with human pain perception and emphasizes its relevance for the multimodal management of pain. PMID- 27681781 TI - Echocardiographic consequences of smoking status in middle-aged subjects. AB - BACKGROUND: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy population. METHODS: Subjects (n=355) from a previous population-based respiratory questionnaire survey (never smokers, ex-smokers, and current smokers without significant chronic obstructive lung disease) were examined with echocardiography, and CI (L/min/m2 ) was calculated. RESULTS: Current smokers had a higher CI than never smokers 2.61+/-0.52 L/min/m2 vs. 2.42+/-0.49 L/min/m2 (P<.01). Ex-smokers had a nonsignificant, numerically higher value for CI than never smokers 2.54+/-0.54 L/min/m2 vs. 2.42+/-0.49 L/min/m2 (P>.05). Smoking status had no significant effect on other echocardiographic variables. CONCLUSION: We conclude that currents smokers without known cardiac disease or significant chronic obstructive lung disease show signs of slightly altered hemodynamics. PMID- 27681782 TI - The cancer vaccine resurgence. PMID- 27681783 TI - FDA eyes new diabetes end points. PMID- 27681784 TI - Merck &Co. drops osteoporosis drug odanacatib. PMID- 27681785 TI - Cardiovascular pipeline decline quantified. PMID- 27681786 TI - New vaccine coalition targets epidemics. PMID- 27681787 TI - Regulatory watch: Evaluating the potential for digital submission of expedited premarket safety reports to the FDA. PMID- 27681788 TI - Market watch: Upcoming market catalysts in Q4 2016. PMID- 27681789 TI - Michael Rosenblatt. PMID- 27681790 TI - Viral infection: New tricks to treat Ebola. PMID- 27681792 TI - Cancer: Tumour-specific ablation of Treg cells induces anticancer response. PMID- 27681791 TI - Antiparasitic drugs: Proteasome inhibition combats kinetoplastid infections. PMID- 27681793 TI - Analgesia: Screening for cleaner pain relief. PMID- 27681794 TI - Inflammatory diseases: Anti-CD1a antibody reduces inflammation in psoriasis. PMID- 27681795 TI - Muscle disorders: Preventing diaphragm dysfunction. PMID- 27681796 TI - Regenerative medicine: Inhibiting Hippo repairs tissue. PMID- 27681797 TI - Cancer: BMI1 inhibition reverses lung cancer. PMID- 27681798 TI - Stroke: Promoting neuronal recovery. PMID- 27681799 TI - Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial. AB - BACKGROUND: Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. METHODS/DESIGN: This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. DISCUSSION: The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. TRIAL REGISTRATION: The trial was registered at www.ClinicalTrials.gov on 18 November 2013. TRIAL REGISTRATION NUMBER: NCT01996579 . PMID- 27681804 TI - Intensive Clinical and Subjective Studies Introduction. PMID- 27681805 TI - Thinking about Things Differently: Commentary on Silverstein and Palumbo. PMID- 27681807 TI - Viable intact cryopreserved human placental membrane for a non-surgical approach to closure in complex wounds. AB - OBJECTIVE: Advances in wound treatment have yielded successful approaches to complex wound closure through plastic surgery or other staged surgical methods. However, not all patients or wounds are candidates for such increasingly rigorous levels of interventions. The exploration of non-surgical treatment options that promote anatomical and functional tissue replacement on an outpatient basis without donor site morbidity is necessary to maximise opportunities for patient mobility and rehabilitation. The native components found in human placental membranes may offer alternative properties for the clinical management of these complex wounds. METHOD: A 10-month, single-centre effectiveness review was conducted on the clinical outcomes in patients (n=12) treated with Grafix, a viable intact cryopreserved human placental membrane (vCPM), for complex wounds characterised by exposed bone, tendon, muscle, or hardware. Wounds were treated with routine standard of care in addition to weekly grafting with a vCPM. RESULTS: The average baseline wound area and duration at presentation were 17.5 cm2 and 11.2 weeks. All twelve cases resulted in granulation over the exposed structures followed by complete wound re-epithelialisation without the concomitant use of negative pressure wound therapy, hyperbaric oxygen therapy, or surgical intervention. The mean 4-week percentage area reduction was 62.5 %. The mean time to closure was 10 weeks with a mean graft use of 8.1 grafts. Of the wounds seven (58%) presented with exposed tendon associated with an actively moving joint, the functional integrity of which was maintained with a return to the previous range of motion upon wound closure. CONCLUSION: These outcomes illustrate that vCPM is a clinically effective option in the non-surgical management of complex wounds in the outpatient setting, contributing to timely definitive closure without the risk of associated donor site morbidity. DECLARATION OF INTEREST: Kazu Suzuki, DPM, CWS is a member of the Speakers' Bureau at Osiris Therapeutics Inc., Georgina Michael and Yeabsera Tamire belong to the Department of Medical Affairs at Osiris Therapeutics Inc. PMID- 27681806 TI - Treatment of large, complex, non-healing wounds with cryopreserved amniotic suspension allograft: a case series. AB - OBJECTIVE: Cryopreserved amniotic suspension allograft (CASA) is a regenerative tissue suspension containing amniotic membrane and amniotic fluid components used for soft-tissue repair, replacement, and reconstruction. The aim of this case series is to examine its effects in different wound types. METHOD: In a retrospective series CASA was applied to chronic non-healing wounds. All patients were treated at a single center between June 2013 and December 2014. The criterion for application of CASA was lack of progress toward wound healing despite standard treatments and adjuvant therapies. RESULTS: We assessed five patients aged between 39 to 86 years old. Three patients had surgical/radiation wounds, one had a sacral pressure ulcer, and one had a diabetic foot ulcer (DFU). All patients experienced progressive improvement in wound area and volume during treatment with CASA. One patient (postmastectomy tissue necrosis) required surgical closure in conjunction with removal of retained sutures. CASA applied topically and subcutaneously was particularly well suited to application in these wounds with large sinus tracts or undermining. All five patients experienced complete wound closure following one to two applications of CASA over 5 to 22 weeks. CONCLUSION: This series highlights the effective use of CASA in recalcitrant large soft-tissue wounds, DFUs, and deep wounds with tendon exposure. DECLARATION OF INTEREST: This study was supported by a grant from Derma Sciences (Princeton, NJ, US). PMID- 27681808 TI - Are chronic wounds, chronic infections? PMID- 27681803 TI - Rescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer's Model. AB - General DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with beta-amyloid load among persons with AD dementia, and PHFtau tangle density. Our results support a plausible causal role for the earliest amyloid beta accumulation to provoke DNA hypomethylation, influencing AD pathological outcomes. PMID- 27681809 TI - Microbiota is a primary cause of pathogenesis of chronic wounds. AB - OBJECTIVE: Diverse microorganisms present on the surface of chronic wounds have been established to constitute wound microbiota. The aims of this study were to quantify the viability of wound microbiota, classify dispersal of viable microbes from the wound, and determine if human wound microbiota can produce a chronic wound in an animal model. METHOD: Wound microbiotas as units (multiple microbial species acting as one infectious agent) were obtained from well-defined human chronic wounds and seeded onto mouse surgical excision wounds to produce chronically infected wounds that closely resembled the chronic wounds observed in the original hosts. RESULTS: We found the wound microbiota harvested from 35 out of 43 (81%) patients could produce similar chronic wounds (producing slough and exudate) in a murine chronic wound model. The top 30 species present in patient wounds were identified in the mouse wounds by molecular sequencing. Koch's postulates could therefore be applied to establish wound microbiota as the cause of the original human chronic wound infections. Evidence-based medicine criteria such as Hill's criteria for causation can all be satisfied by what is currently known about wound microbiota. CONCLUSION: This study demonstrates that wound microbiota actively disseminates from the chronic wound by forces and mechanisms intrinsic to the wound. Koch's postulates and Hill's criteria for causation together suggest chronic wound microbiota to be the main cause underlying the pathogenesis of chronic wounds. DECLARATION OF INTEREST: RW has an equity interest in PathoGenius Labs. No funding was received for this study. PMID- 27681810 TI - Thoracoabdominal necrotising soft tissue infection secondary to enterocutaneous fistulae: a case report. AB - OBJECTIVE: Necrotising soft tissue infection is a rare surgical emergency, which requires immediate and aggressive surgical debridement. Following control of the infection, patients are often left with large defects, with wound reconstruction and closure creating significant challenges. Here we describe a case of extensive thoracoabdominal necrotising soft tissue infection and provide a discussion on the standard of care and treatment based on a current literature review. METHOD: A 53-year-old female presented with bilious and feculent discharge from her surgical incision two weeks after a total abdominal hysterectomy. She was found to have two enterocutaneous fistulae and an extensive abdominal wall necrotising soft tissue infection extending to the lower thorax. Wide excision and debridement were performed, leaving a large triangular defect. Following serial washouts and debridements, a biologic mesh with openings for the enterocutaneous fistulae was used to cover the fascial defect Results: Postoperatively, the patient was discharged to a nursing facility where she remained on total parenteral nutrition due to high fistula output. She subsequently underwent fistulectomy nine months later followed by skin grafting. To date, she has not had any recurrent fistulae or infection. CONCLUSION: Necrotising soft tissue infection resulting in a large abdominal wall defect secondary to enterocutaneous fistulae poses a significant challenge for source control and abdominal wall reconstruction. After serial debridements, use of biologic mesh for temporary closure followed by staged resection of the bowel with abdominal wall reconstruction can be performed. DECLARATION OF INTEREST: The authors have no personal financial or institutional interest in any of the drugs, materials, or devices used. PMID- 27681811 TI - A comparative analysis of skin substitutes used in the management of diabetic foot ulcers. AB - OBJECTIVE: To compare the relative product cost and clinical outcomes of four skin substitutes used as adjunctive treatments for diabetic foot ulcers (DFUs). METHOD: Medicare claims data from 2011 to 2014 were used to identify beneficiaries with diabetes and foot ulcers. Patients treated with one of four types of skin substitute (Apligraf, Dermagraft, OASIS, and MatriStem) were identified. The skin substitutes were compared on episode length; amputation rate; skin substitute utilisation; and skin substitute costs. RESULTS: There were 13,193 skin substitute treatment episodes: Apligraf (HML) was used in 4926 (37.3%), Dermagraft (HSL) in 5530 (41.9%), OASIS (SIS) in 2458 (18.6%) and MatriStem (UBM) in 279 (2.1%). The percentage of DFUs that healed at 90 days were: UBM 62%; SIS 63%; HML 58%; and HSL 58%. Over the entire time, UBM was non inferior to SIS (p<0.001), and either was significantly better than HML or HSL (p<0.005 in all four tests). HML was marginally superior to HSL (p=0.025 unadjusted for multiple testing). Medicare reimbursements for skin substitutes per DFU episode for UBM ($1435 in skin substitutes per episode) and SIS ($1901) appeared to be equivalent to each other, although non-inferiority tests were not significant. Both were less than HML ($5364) or HSL ($14,424) (p<0.0005 in all four tests). HML was less costly than HSL (p<0.0005). CONCLUSION: Various types of skin substitutes appear to be able to confer important benefits to both patients with DFUs and payers. Analysis of the four skin-substitute types resulted in a demonstration that UBM and SIS were associated with both shorter DFU episode lengths and lower payer reimbursements than HML and HSL, while HML was less costly than HSL but equivalent in healing. DECLARATION OF INTEREST: MM and NM are health economic consultants who completed and authored this analysis. They have no financial interest in ACell, Inc. Their fees were not contingent on the outcome of this analysis. PMID- 27681812 TI - A multilevel nonvolatile magnetoelectric memory. AB - The coexistence and coupling between magnetization and electric polarization in multiferroic materials provide extra degrees of freedom for creating next generation memory devices. A variety of concepts of multiferroic or magnetoelectric memories have been proposed and explored in the past decade. Here we propose a new principle to realize a multilevel nonvolatile memory based on the multiple states of the magnetoelectric coefficient (alpha) of multiferroics. Because the states of alpha depends on the relative orientation between magnetization and polarization, one can reach different levels of alpha by controlling the ratio of up and down ferroelectric domains with external electric fields. Our experiments in a device made of the PMN-PT/Terfenol-D multiferroic heterostructure confirm that the states of alpha can be well controlled between positive and negative by applying selective electric fields. Consequently, two level, four-level, and eight-level nonvolatile memory devices are demonstrated at room temperature. This kind of multilevel magnetoelectric memory retains all the advantages of ferroelectric random access memory but overcomes the drawback of destructive reading of polarization. In contrast, the reading of alpha is nondestructive and highly efficient in a parallel way, with an independent reading coil shared by all the memory cells. PMID- 27681813 TI - Clinical comparison of oral administration and viscosupplementation of hyaluronic acid (HA) in early knee osteoarthritis. AB - PURPOSE: Osteoarthritis (OA) is a progressive, chronic and degenerative joint disease characterized by a loss of articular cartilage. Treatment of OA is largely palliative based on nonsteroidal anti-inflammatory drugs, opioids and injections of steroids. Regarding conservative treatment, intra-articular injections of hyaluronic acid (HA) can play a role in early symptomatic knee OA. MATERIALS AND METHODS: Between August 2015 and September 2015, sixty patients (32 males and 28 females) between 40 and 70 years old were randomly allocated into two groups: Half were treated with three weekly intra-articular injections of hyaluronic acid 1.6 % (group A), while the others were treated with Syalox 300 Plus(r) (hyaluronic acid 300 mg + Boswellia serrata extract 100 mg) 1 tab/die for 20 days and afterward Syalox 150(r) (hyaluronic acid 150 mg) 1 tab/die for other 20 days (group B). All patients were evaluated clinically with American Knee Society Score (AKSS) and visual analogue scale (VAS) for the pain before the treatment and after 3 months. RESULTS: AKSS of the patients in both groups was significantly increased by the treatment, and VAS score was significantly reduced. In both groups, two subgroups were created with patients older than 60 years and patients younger than 60 years. Better results are reported in younger patients of group A and older subjects in group B. CONCLUSIONS: Despite several limitations, the results of the study have shown that HA injection and oral administration may have beneficial therapeutic effects on patients with early osteoarthritis. Different outcomes in younger and older subject suggested a combined therapy first with local infiltrations and then with oral composition. PMID- 27681816 TI - Application of Freezing and Thawing in Apple (Malus domestica) Juice Extraction. AB - The paper presents the results of the research on the impact of enzymatic liquefaction, freezing and thawing on the efficiency of juice pressure extraction from apple pulp and quality of the obtained juices. The research was conducted using three types of pretreatment prior the pressing: crushing and enzymatic liquefaction in temperature of 25 degrees C, crushing and enzymatic liquefaction in temperature of 45 degrees C and crushing followed by freezing and thawing of the pulp. The study included three varieties of apples. The juice was obtained using a laboratory basket press. It was determined that the pretreatment of the pulp as well as the varietal characteristics of the fruits have a significant impact on the efficiency of the pressure extraction process. The enzymatic treatment of the pulp, irrespective of the temperature at which it was conducted, significantly increased the efficiency of the process. No effect of the temperature (25 or 45 degrees C) of enzymatic treatment on the efficiency of the pressure extraction process was found. Pretreatment of the pulp based on freezing and thawing contributes to the increase of efficiency of pressing in the case of two apple cultivars, that is, Idared and Red Delicious. It was showed that total phenolic content, antioxidant activity, the soluble solids content and juice acidity (pH) depend on the pretreatment of the pulp and the varietal characteristics of apples. Following the application of pretreatment of the pulp, an increase was observed in the content of polyphenols and in the antioxidant activity of the juices obtained. PMID- 27681815 TI - Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study. AB - The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men. PMID- 27681814 TI - Serologic and radiographic outcome of total hip arthroplasty with CoCr modular neck at mid-term follow-up. AB - PURPOSE: The aim of this study is a radiographic evaluation and to determine serologic values of chromium and cobalt in the blood and urine of patients who have been implanted with a Stryker(r) ABG II Modular Neck and see if there is correlation with the features of prosthesis and patients. METHODS: The study involves the collection of data from patients operated on for total hip model with the ABG II Modular Neck with a minimum follow-up of 1 year. RESULTS: We evaluated 22 patients who underwent implantation of a hip prosthesis with modular neck in CoCr. Of these, the average Cr in the blood was 0.63 MUgL-1 (range 0.1 2.15 MUgL-1), the average of Co in the blood was 3.50 MUgL-1 (range 0.62-7.78 MUgL-1), the average Cr in the urine was 1.24 MUgL-1 (range 0.48-2.21 MUgL-1), and the average Co in urine was 14.22 MUgL-1 (range 3.3-31.2 MUgL-1). None of these patients had undergone revision surgery. CONCLUSIONS: Our study seems to indicate that the restoration of offset and age are correlated with the release of metal ions, although the correlation is weak and needs better methodological studies and a greater number of patients to confirm this hypothesis. STUDY TYPE: Case series Level of Evidence 4. PMID- 27681818 TI - Understanding interprofessional collaboration in the context of chronic disease management for older adults living in communities: a concept analysis. AB - AIM: To report a concept analysis of interprofessional collaboration in the context of chronic disease management, for older adults living in communities. BACKGROUND: Increasing prevalence of chronic disease among older adults is creating significant burden for patients, families and healthcare systems. Managing chronic disease for older adults living in the community requires interprofessional collaboration across different health and other care providers, organizations and sectors. However, there is a lack of consensus about the definition and use of interprofessional collaboration for community-based chronic disease management. DESIGN: Concept analysis. DATA SOURCES: Electronic databases CINAHL, Medline, HealthStar, EMBASE, PsychINFO, Ageline and Cochrane Database were searched from 2000 - 2013. METHODS: Rodgers' evolutionary method for concept analysis. RESULTS: The most common surrogate term was interdisciplinary collaboration. Related terms were interprofessional team, multidisciplinary team and teamwork. Attributes included: an evolving interpersonal process; shared goals, decision-making and care planning; interdependence; effective and frequent communication; evaluation of team processes; involving older adults and family members in the team; and diverse and flexible team membership. Antecedents comprised: role awareness; interprofessional education; trust between team members; belief that interprofessional collaboration improves care; and organizational support. Consequences included impacts on team composition and function, care planning processes and providers' knowledge, confidence and job satisfaction. CONCLUSION: Interprofessional collaboration is a complex evolving concept. Key components of interprofessional collaboration in chronic disease management for community-living older adults are identified. Implications for nursing practice, education and research are proposed. PMID- 27681817 TI - Multiple imaging modalities for the detection of optic nerve head drusen: Is echography still mandatory? PMID- 27681819 TI - Intermittent pneumatic compression in laparoscopic surgery for prevention of deep vein thrombosis and cellular damage from iatrogenic compartment syndrome. AB - AIM: This study is aimed to evaluate the incidence of the postoperative deep vein thrombosis (DVT) and the cell damage from compartment iatrogenic syndrome, analyzing two groups of patients operated laparoscopically, one of which assisted with a Sequential Compression Device (SCD). MATERIAL OF STUDY: A patients' series submitted to laparoscopic surgery over a period at least 90 minutes. The venous flow in the lower limbs was detected with the Echo Colour Doppler method, and only one of the two groups was assisted with the SCD. RESULTS: Between November 2006 and October 2007, 35 patients were evaluated, 21 of them wew assisted with SDC and the remaining 14 patients were the control group. All patients had a follow-up was extended for 5 years at the interval of 7 days, 14 days, 30 days, 3 and 5 years. DISCUSSION: The results were confirmed that the application of SCD is able to neutralize the negative effect of the PNP reducing the possible risk of thromboembolic venous stasis and the improvement of lactic acid and of myoglobinemia are attributable to a reduction of preload. With the use of IPC, it decreases venous stasis, improves venous return and cardiac output increases, preventing cell damage by hypoperfusion. CONCLUSIONS: The use of a SCD applied to the lower limbs allows an increase in venous return from the lower limbs so reducing the risk of DVT. KEY WORDS: Cellular damage, DVT, Pneumoperitoneum. PMID- 27681820 TI - Estimating the reliability of repeatedly measured endpoints based on linear mixed effects models. A tutorial. AB - There are various settings in which researchers are interested in the assessment of the correlation between repeated measurements that are taken within the same subject (i.e., reliability). For example, the same rating scale may be used to assess the symptom severity of the same patients by multiple physicians, or the same outcome may be measured repeatedly over time in the same patients. Reliability can be estimated in various ways, for example, using the classical Pearson correlation or the intra-class correlation in clustered data. However, contemporary data often have a complex structure that goes well beyond the restrictive assumptions that are needed with the more conventional methods to estimate reliability. In the current paper, we propose a general and flexible modeling approach that allows for the derivation of reliability estimates, standard errors, and confidence intervals - appropriately taking hierarchies and covariates in the data into account. Our methodology is developed for continuous outcomes together with covariates of an arbitrary type. The methodology is illustrated in a case study, and a Web Appendix is provided which details the computations using the R package CorrMixed and the SAS software. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27681821 TI - Mesenchymal stem cells and vascular regeneration. AB - In recent years, MSCs have emerged as a promising therapeutic cell type in regenerative medicine. They hold great promise for treating cardiovascular diseases, such as myocardial infarction and limb ischemia. MSCs may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits to patients. The efficacy of MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Increasing our understanding of the mechanisms of MSC involvement in vascular regeneration will be beneficial in boosting present therapeutic approaches and developing novel ones to treat cardiovascular diseases. In this review, we aim to summarize current progress in characterizing the in vivo identity of MSCs, to discuss mechanisms involved in cell-based therapy utilizing MSCs, and to explore current and future strategies for vascular regeneration. PMID- 27681822 TI - Topographic generation of submesoscale centrifugal instability and energy dissipation. AB - Most of the ocean kinetic energy is contained in the large scale currents and the vigorous geostrophic eddy field, at horizontal scales of order 100 km. To achieve equilibrium the geostrophic currents must viscously dissipate their kinetic energy at much smaller scale. However, geostrophic turbulence is characterized by an inverse cascade of energy towards larger scale, and the pathways of energy toward dissipation are still in question. Here, we present a mechanism, in the context of the Gulf Stream, where energy is transferred from the geostrophic flow to submesoscale wakes through anticyclonic vertical vorticity generation in the bottom boundary layer. The submesoscale turbulence leads to elevated local dissipation and mixing outside the oceanic boundary layers. This process is generic for boundary slope currents that flow in the direction of Kelvin wave propagation. Topographic generation of submesoscale flows potentially provides a new and significant route to energy dissipation for geostrophic flows. PMID- 27681824 TI - Neuroanatomy and Neurophysiology: Implications for Swallowing. AB - Deglutition is a complicated neuromuscular process that requires a complex level of communication between the central and peripheral nervous systems, and which results in highly coordinated actions from the muscles of mouth, pharynx, larynx, and esophagus. The actions of the individual muscles involved in deglutition and their cranial nerve innervation for the oral and pharyngeal stages of the swallow are presented. This is followed by a discussion of the research relating to potential areas of breakdown, and the corresponding symptomology, associated with the oral and pharyngeal stages of swallowing following a stroke. PMID- 27681825 TI - Evaluating Swallowing Disorders: The Speech-Language Pathologist's Perspective. AB - A comprehensive evaluation of swallowing is critical for identifying the presence of a dysphagia, the stage of dysfunction, and the underlying cause of difficulty, as well as for determining the risk for aspiration. This article reviews the procedures of the evaluation, typically conducted by a speech-language pathologist. The evaluation includes a complete history of the problem, a clinical swallowing evaluation, and a video- fluorographic assessment (or other instrumental assessment) of the swallowing mechanism. The results of the evaluation al low the clinician to determine an appropriate individualized management plan. PMID- 27681823 TI - Single sample resolution of rare microbial dark matter in a marine invertebrate metagenome. AB - Direct, untargeted sequencing of environmental samples (metagenomics) and de novo genome assembly enable the study of uncultured and phylogenetically divergent organisms. However, separating individual genomes from a mixed community has often relied on the differential-coverage analysis of multiple, deeply sequenced samples. In the metagenomic investigation of the marine bryozoan Bugula neritina, we uncovered seven bacterial genomes associated with a single B. neritina individual that appeared to be transient associates, two of which were unique to one individual and undetectable using certain "universal" 16S rRNA primers and probes. We recovered high quality genome assemblies for several rare instances of "microbial dark matter," or phylogenetically divergent bacteria lacking genomes in reference databases, from a single tissue sample that was not subjected to any physical or chemical pre-treatment. One of these rare, divergent organisms has a small (593 kbp), poorly annotated genome with low GC content (20.9%) and a 16S rRNA gene with just 65% sequence similarity to the closest reference sequence. Our findings illustrate the importance of sampling strategy and de novo assembly of metagenomic reads to understand the extent and function of bacterial biodiversity. PMID- 27681826 TI - Treating Swallowing Disorders following Stroke. AB - The speech-language pathologist uses a combination of direct and indirect treatment techniques to manage dysphagia in the patient with a stroke. This article reviews a variety of these procedures, including patient and family education, sensory stimulation techniques such as modifications in bolus characteristics and thermal stimulation, compensatory postures and positioning, compensatory swallowing maneuvers, and physiotherapeutic techniques. General guidelines for selection of appropriate techniques based on clinical presentation and underlying symptoms are discussed. PMID- 27681827 TI - Dysphagia Resulting from Esophageal Problems. AB - Common symptoms, diagnostic techniques, and management methods for patients who have dysphagia of esophageal origin are reviewed. Esophageal problems are usually present premorbidly, but may manifest themselves after a stroke occurs. Esophageal abnormalities may mimic or exacerbate oropharyngeal symptoms of dysphagia. Therefore, the anatomy, physiology, and diagnostic tools to examine the esophagus must be appreciated in order to recognize symptoms and choose appropriate treatment strategies for esophageal disorders. Despite the high mortality and morbidity of some esophageal diseases, proper diagnosis and treatment may al low the stroke survivor to maintain adequate oral caloric intake without discomfort or nonoral feeding methods. PMID- 27681828 TI - Nutritional Considerations for the Stroke Patient with Dysphagia. AB - Dysphagia is a physical disability that negatively affects patients' abilities to meet their nutritional needs. Dysphagia may result in anorexia, weight loss, protein-energy malnutrition, and vitamin and mineral deficiencies. Dehydration is also a major risk. Swallowing abnormalities have been observed in 25% to 50% of patients following a stroke. The dietitian's role in assessingthe nutritional status of dysphagic patients and in working with the interdisciplinary team isessential to comprehensive patient care. A Nutrition Assessment Form is presented for stroke patients, and recommendations are made for dysphagic diets and feeding management for the interdisciplinary team. Increasing food consumption is critical to improving nutritional status and quality of life for those receiving rehabilitation services. PMID- 27681829 TI - Hemiplegia and Feeding: An Occupational Therapy Approach to Upper Extremity Management. AB - Stroke survivors with resulting hemiplegia may have difficulty performing feeding tasks independently. This article describes the occupational therapist's role in helping patients achieve improved functional performance during feeding. It provides an overview of motor abilities required for self-feeding, describes abnormal movements typically seen in stroke patients, and discusses assessments and therapeutic interventions commonly used in occupational therapy. A case study is presented to illustrate the use of these therapeutic interventions. PMID- 27681830 TI - Ethical Dilemmas in Dysphagia Practice. PMID- 27681831 TI - Foreword. PMID- 27681832 TI - 1-D "Platinum Wire" Stacking Structure Built of Platinum(II) Diimine Bis(sigma acetylide) Units with Luminescence in the NIR Region. AB - A square-planar platinum(II) complex, Pt(DiBrbpy)(C=CC6H4Et-4)2 (1) (DiBrbpy = 4,4-dibromo-2,2'-bipyridine), and crystals of its three solvated forms, namely, 1.DMSO, 1.1/2(CH3CN), and 1.1/8(CH2Cl2), were developed and characterized. 1.DMSO and 1.1/2(CH3CN) contain quasi-dimeric and dimeric structures with luminescence in the visible range, whereas 1.1/8(CH2Cl2) exhibits NIR luminescence at 1022 nm due to its intrinsic 1-D "platinum wire" stacking structure with strong Pt-Pt interactions. 1.1/8(CH2Cl2) represents the first compound based on platinum(II) diimine bis(sigma-acetylide) molecular units with the NIR luminescence beyond 1000 nm. 1 selectively responds to DMSO and CH3CN by changing its color and luminescence property and the three solvated forms can be reversibly converted to each other upon exposure to corresponding solvent vapors. Their desolvated forms, namely 1a, 1b, and 1c, obtained after heating 1.DMSO, 1.1/2(CH3CN), and 1.1/8(CH2Cl2), respectively, can also be restored to the original solvated forms upon exposure to corresponding solvent vapors. 1a and 1b emit NIR luminescence peaked at 998 and 1018 nm respectively, suggesting indirect synthetic methods as powerful alternatives to achieve NIR luminescence with long wavelength. In contrast, 1c exhibits a red luminescence with a broad unstructured emission band centered at 667 nm. All the responses to organic solvent vapors and heating are due to the structural transformations which result in the conversion of the lowest energy excited states between 3MLCT/3LLCT and 3MMLCT in solid-state as supported by time-dependent density functional theory (TD-DFT) calculations. PMID- 27681833 TI - Novel oral anticoagulants for atrial fibrillation. PMID- 27681834 TI - o-Naphthoquinone-Catalyzed Aerobic Oxidation of Amines to (Ket)imines: A Modular Catalyst Approach. AB - A modular aerobic oxidation of amines to imines has been achieved using an ortho naphthoquinone (o-NQ) catalyst. The cooperative catalyst system of o-NQ and Cu(OAc)2 enabled the formation of homocoupled imines from benzylamines, while the presence of TFA helped the formation of cross-coupled imines in excellent yields. The current mild aerobic oxidation protocol could also be applied to the oxidation of secondary amines to imines or ketimines with the help of cocatalyst, Ag2CO3, with excellent yields. PMID- 27681837 TI - Comparison of methods used to quantify general practice-type patients in the emergency department: A tertiary paediatric perspective. AB - OBJECTIVE: The aim of this study was to compare methods for quantifying general practice-type (GP-type) patients in a paediatric ED to determine the robustness of current identification methods. METHODS: Data was sourced from the ED Information System for 5 years (2010-2014) from the tertiary paediatric hospital in Perth, Western Australia, Australia. A further detailed analysis of 2014 presentations established an independent sample for valid statistical comparison of the three methods used to identify GP-type patients: Australian Institute of Health and Welfare, ACEM and the Diagnosis. RESULTS: A total of 348 020 patients presented in 2010-2014, with the percentage of GP-type patients identified varying from 38% to 68% by the three methods. Fewer GP-type presentations occurred over each consecutive year and had significantly lower median medical consultation times and ED length of stay when compared with the total presentation sample. GP-type presentations were evenly spread across the days and times of the week, with ACEM demonstrating only fewer presentations during office hours (P = 0.02). In 2014 there was only overlap in 36.6% cases for all three methods - 6.9% exclusively flagged by ACEM, 22.7% by Australian Institute of Health and Welfare and 0.2% by the Diagnosis method. CONCLUSIONS: We demonstrated that current models to quantify perceived GP-type presentations were inconsistent in paediatric patients. All methods flagged a high proportion of GP-type presentations, and although the reasons for these presentations are multifactorial and not easily explained by access to GP services alone, they do represent a significant workload in the paediatric ED. PMID- 27681839 TI - Health promotion among older adults in Austria: a qualitative study. AB - AIMS AND OBJECTIVES: To determine the types of attitudes to health promotion among older Austrians. BACKGROUND: Health promotion in old age becomes increasingly important in the current period of demographic transition. Interventions are likely to be successful if they take the attitude of older persons into consideration. There may be several types of attitudes to health promotion among older adults. DESIGN: Cross-sectional qualitative study. METHODS: Semi-structured interviews were conducted in a purposive sample consisting of 36 home-dwelling older persons from local communities in the federal province of Salzburg, Austria. Data were analysed using qualitative content analysis according to Mayring and subsequent construction of types. RESULTS: There are three main types of attitudes to health promotion. 'Health promoters through everyday activities' considered domestic work and walks to be sufficient in keeping up their health. Fitness-oriented persons practised sports of some type. Users of complementary methods practised such methods to some degree. These types of attitudes could be further differentiated according to their outcome expectations. In addition to benefits for health, socialising was also an important outcome. Physical decline may reduce a fitness-oriented attitude, whereas encouragement by others may trigger it. CONCLUSION: Older adults have various attitudes to health promotion, but these are not immutable. RELEVANCE TO CLINICAL PRACTICE: Health promotion programmes that are not restricted to a narrow focus on health but provide the opportunity to socialise may support older adults in maintaining a healthy lifestyle. PMID- 27681838 TI - Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury. AB - Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11.37 +/- 1.59 MUg/mL). Using bioactivity-guided fractionation, one new compound and 23 known compounds were identified. Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC50, 1.86 +/- 0.06 MUM). In a cell based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils. In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases. PMID- 27681841 TI - Relation between blood vitamin B12 levels with premature ejaculation: case control study. AB - The aim of this study was to investigate whether vitamin B12 levels are associated with premature ejaculation (PE). A total of 109 subjects (56 PE and 53 controls) were included in this study. PE was defined as self-reported intravaginal ejaculatory latency time (IELT) based on the Diagnostic and Statistical Manual of Mental Disorders IV criteria and those who had had an IELT of <2 min was considered as PE. All participants were evaluated using premature ejaculation diagnostic tool (PEDT), International Index of Erectile Function (IIEF) and Beck Depression Inventory (BDI). The vitamin 12 levels were measured in all subjects. The mean age between the PE and controls was comparable (p = .084). Mean IIEF and BDI scores between the two groups did not statistically differ. The mean IELT values in the PE group were significantly lower than in the control group (p < .0001). PE patients reported significantly lower vitamin B12 levels compared with the controls (213.14 vs. 265.89 ng ml-1 ; p < .001). The ROC analysis showed a significant correlation between the diagnosis of PE and lower vitamin B12 levels. This study has demonstrated that lower vitamin B12 levels are associated with the presence of PE. This work also shows a strong correlation between vitamin B12 levels and the PEDT scores as well as the IELT values. PMID- 27681843 TI - Follicular proliferation or basal cell carcinoma? The first prospective U.K. study of this histological challenge during Mohs surgery. PMID- 27681844 TI - Letter to the Editor: Bias in the measurement of bias. Letter regarding 'Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression'. PMID- 27681842 TI - Preoperative risk factors for intra-operative bleeding in pediatric liver transplantation. AB - This study analyzes the preoperative risk factors for intra-operative bleeding in our recent series of pediatric LTs. Between November 2009 and November 2014, 84 consecutive isolated pediatric LTs were performed in 81 children. Potential preoperative predictive factors for bleeding, amount of intra-operative transfusions, postoperative course, and outcome were recorded. Cutoff point for intra-operative HBL was defined as intra-operative RBC transfusions >=1 TBV. Twenty-six patients (31%) had intra-operative HBL. One-year patient survival after LT was 66.7% (CI 95%=[50.2-88.5]) in HBL patients and 83.8% (CI 95%=[74.6 94.1]) in the others (P=.054). Among 13 potential preoperative risk factors, three of them were identified as independent predictors of high intra-operative bleeding: abdominal surgical procedure(s) prior to LT, factor V level <=30% before transplantation, and ex situ parenchymal transsection of the liver graft. Based on these findings, we propose a simple score to predict the individual hemorrhagic risk related to each patient and graft association. This score may help to better anticipate intra-operative bleeding and improve patient's management. PMID- 27681840 TI - Regulation of divalent metal transporter-1 by serine phosphorylation. AB - Divalent metal transporter-1 (DMT1) mediates dietary iron uptake across the intestinal mucosa and facilitates peripheral delivery of iron released by transferrin in the endosome. Here, we report that classical cannabinoids (Delta9 tetrahydrocannabinol, Delta9-THC), nonclassical cannabinoids (CP 55,940), aminoalkylindoles (WIN 55,212-2) and endocannabinoids (anandamide) reduce 55Fe and 54Mn uptake by HEK293T(DMT1) cells stably expressing the transporter. siRNA knockdown of cannabinoid receptor type 2 (CB2) abrogated inhibition. CB2 is a G protein (GTP-binding protein)-coupled receptor that negatively regulates signal transduction cascades involving serine/threonine kinases. Immunoprecipitation experiments showed that DMT1 is serine-phosphorylated under basal conditions, but that treatment with Delta9-THC reduced phosphorylation. Site-directed mutation of predicted DMT1 phosphosites further showed that substitution of serine with alanine at N-terminal position 43 (S43A) abolished basal phosphorylation. Concordantly, both the rate and extent of 55Fe uptake in cells expressing DMT1(S43A) was reduced compared with those expressing wild-type DMT1. Among kinase inhibitors that affected DMT1-mediated iron uptake, staurosporine also reduced DMT1 phosphorylation confirming a role for serine phosphorylation in iron transport regulation. These combined data indicate that phosphorylation at serine 43 of DMT1 promotes transport activity, whereas dephosphorylation is associated with loss of iron uptake. Since anti-inflammatory actions mediated through CB2 would be associated with reduced DMT1 phosphorylation, we postulate that this pathway provides a means to reduce oxidative stress by limiting iron uptake. PMID- 27681845 TI - Adherence to recommended UK sampling protocols for detecting mast cell mediator release in perioperative anaphylaxis. AB - BACKGROUND: Sheffield National Adverse Reactions Consultancy Service (NARCOS) investigates and triages suspected perioperative anaesthetic reactions to allergy clinics, using serial tryptase samples, urinary methylhistamine and clinical information on a pro forma request. OBJECTIVE: To determine if current UK guidelines on serial tryptase samples are achieved and describe the patterns of tryptase release. METHOD: A retrospective review of 3455 NARCOS cases. Tryptase and clinical details were analysed. 1746 had sufficient clinical information to grade the reactions according to the Ring and Messmer scale. RESULTS: 98% provided two or more acute samples, but only 60% supplied clinical information. 308 patients never dropped within the reference range over three samples. CONCLUSIONS: Good compliance with UK guidelines for tryptase measurements is achievable in this long-term cohort, but obtaining clinical details at referral remains a challenge. Sample sequence labelling and apparent timing may be misleading. Baseline tryptase may frequently need to be rechecked in allergy clinics to estimate true peak-to-trough changes. PMID- 27681846 TI - How close are we to standardised extended RAS gene mutation testing? The UK NEQAS evaluation. AB - AIMS: Since 2008, KRAS mutation status in exon 2 has been used to predict response to anti-EGFR therapies. Recent evidence has demonstrated that NRAS status is also predictive of response. Several retrospective 'extended RAS' analyses have been performed on clinical trial material. Despite this, are we really moving towards such extended screening practice in reality? METHODS: Data were analysed from four consecutive UK National External Quality Assessment Service for Molecular Genetics Colorectal cancer External Quality Assessment schemes (during the period 2014-2016), with up to 110 laboratories (worldwide) participating in each scheme. Testing of four or five tumour samples is required per scheme. Laboratories provided information on which codons were routinely screened, and provided genotyping and interpretation results for each sample. RESULTS: At least 85% of laboratories routinely tested KRAS codons 12, 13 and 61. Over the four schemes, an increasing number of laboratories routinely tested KRAS codons 59, 117 and 146. Furthermore, more laboratories were introducing next generation sequencing technologies. The pattern of 'extended testing' was reassuringly similar for NRAS, although fewer laboratories currently test for mutations in this gene. Alarmingly, still only 36.1% and 24.1% of participating laboratories met the ACP Molecular Pathology and Diagnostics Group and American Society of Clinical Oncology guidelines, respectively, for extended RAS testing in the latest assessment. CONCLUSIONS: Despite recommendations in the UK and USA on extended RAS testing, there has clearly been, based on these results, a delay in implementation. Inadequate testing results in patients being subjected to harmful treatment regimens, which would not be the case, were routine practice altered, in line with evidence-based guidelines. PMID- 27681847 TI - Regression grading in neoadjuvant treated pancreatic cancer: an interobserver study. AB - AIM: Several regression grading systems have been proposed for neoadjuvant chemoradiation-treated pancreatic ductal adenocarcinoma (PDAC). This study aimed to examine the utility, reproducibility and level of concordance of three most frequently used grading systems. METHODS: Four gastrointestinal pathologists used the College of American Pathologists (CAP), Evans, MD Anderson Cancer Centre (MDA) regression grading systems to grade 14 selected cases (7-20 slides from each case) of neoadjuvant chemoradiation-treated PDAC. A postscoring discussion with each pathologist was conducted. The results were entered into a standardised data collection form and statistical analyses were performed. RESULTS: There was little concordance across the three systems. The Kendall coefficient of concordance agreement scores were: CAP: 2-poor, 2-fair; Evans: 1-fair, 1 moderate, 2-good; MDA: 1-poor, 2-moderate, 1-good. Interpretation in all three grades in the CAP grading system was a source of discrepancy. Furthermore, using fibrosis as a criterion to assess regression was contentious. In the Evans system, quantifying tumour destruction using arbitrary percentage cut-offs (ie, 9% vs 10%; 50% vs 51%, etc) was imprecise and subjective. Although the MDA system generated greatest concordance, this was due to 'oversimplification' surrounding wide, arbitrarily assigned thresholds of 5% of tumour. CONCLUSIONS: All systems lacked precision and clarity for accurate regression grading. Presently the clinical utility and impact of histological regression grading in patient management is questionable. There is a need to re-evaluate regression grading in the pancreas and establish a reproducible, clinically relevant grading system. PMID- 27681848 TI - Type 1 diabetes risk in children born to women with fertility problems: a cohort study in 1.5 million Danish children. AB - INTRODUCTION: While some studies have indicated that children born following fertility treatment are at an increased risk for insulin resistance and higher blood glucose levels, no study to date has investigated the risk of type 1 diabetes. In this large population-based cohort study we aim to assess the association between maternal fertility problems and the risk of type 1 diabetes in children. MATERIAL AND METHODS: Information on all children, born in Denmark from 1987 to 2010, was extracted from the Civil Registration System and linked with the Danish Infertility Cohort to identify maternal fertility status. Diabetes information was obtained from the National Patient Register and the Childhood Diabetes Register. A Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals. RESULTS: A total of 1 550 519 children made up the study cohort, of whom 110 393 (7.1%) were born to women with fertility problems. In all, 313 children born to women with fertility problems (0.36%) and 5176 children born to women without fertility problems (0.28%) were diagnosed with type 1 diabetes. The risk of type 1 diabetes was not affected by maternal fertility status (hazard ratio 1.01, 95% CI 0.90-1.13) when taking into account birth year, sex, history of parental diabetes, parental age and age at diagnosis. CONCLUSIONS: Our results showed no association between maternal fertility problems and risk of type 1 diabetes in children. PMID- 27681849 TI - Evaluation of Knee Pain in Athletes: A Radiologist's Perspective. AB - Lower limb injuries account for most of all injuries suffered by athletes and the knee joint accounts for over half of these. The etiology of knee pain is multifactorial; a good history focusing on the mechanism of injury and the chronicity of pain is extremely useful in correlating with radiologic findings and establishing a clinically meaningful diagnosis. This review article will discuss several important and common causes of acute and chronic knee pain in athletes, focusing on their mechanism of injury and site of pain as well as their salient imaging findings. PMID- 27681850 TI - Preoperative Imaging in Primary Hyperparathyroidism: Literature Review and Recommendations. PMID- 27681851 TI - Differing Isomerization Kinetics of Azobenzene-Functionalized Self-Assembled Monolayers in Ambient Air and in Vacuum. AB - Azobenzene-alkanethiols in self-assembled monolayers (SAMs) on Au(111) exhibit reversible trans-cis photoisomerization when diluted with alkanethiol spacers. Using these mixed SAMs, we show switching of the linear optical and second harmonic response. The effective switching of these surface optical properties relies on a reasonably large cross section and a high photoisomerization yield as well as a long lifetime of the metastable cis isomer. We quantified the switching process by X-ray absorption spectroscopy. The cross sections for the trans-cis and cis-trans photoisomerization with 365 and 455 nm light, respectively, are one order of magnitude smaller than in solution. In vacuum the 365 nm photostationary state comprises 50-74% of the molecules in the cis form, limited by their rapid thermal isomerization back to the trans state. In contrast, the 455 nm photostationary state contains nearly 100% trans-azobenzene. We determined time constants for the thermal cis-trans isomerization of only a few minutes in vacuum and in a dry nitrogen atmosphere, but of more than one day in ambient air. Our results suggest that adventitious water adsorbed on the SAM's surface stabilizes the polar cis configuration of azobenzene under ambient conditions. The back reaction rates differing by two orders of magnitude underline the huge influence of the environment and accordingly its importance when comparing various experiments. PMID- 27681852 TI - Emergency Preparedness for a Mass Gathering: the 2015 Papal Visit to Philadelphia. AB - In September 2015, Pope Francis visited Philadelphia, Pennsylvania, and led outdoor events over the course of 2 days. As a result, The Children's Hospital of Philadelphia (CHOP) was faced with the challenge of planning for and responding to a mass gathering that was anticipated to be one of the largest in US history. As a result of unprecedented traffic restrictions, it was anticipated that patients, staff, and vendors would have severe challenges accessing the hospital, along with impaired communications from widespread cell phone service disruption. Previous mass gatherings have proven a need for early, detailed planning with multidisciplinary stakeholders, but little has been published on the impact of mass gatherings on area hospitals. This lack of data makes it difficult to predict the extent to which demand for hospital services would be increased and which services would be most affected. Early, coordinated planning allowed CHOP leaders to delegate responsibilities to those with specific expertise, prioritize needs, prevent duplication of efforts, and ensure engagement and accountability from key stakeholders. Emergency preparedness-led efforts including housing almost 1000 employees for 3 consecutive nights and assisting families with access allowed our hospital to maintain operations. The planning strategies shared here will provide emergency preparedness planners with a blueprint for future mass gathering preparedness. (Disaster Med Public Health Preparedness. 2017;11:267 276). PMID- 27681853 TI - Comparative Assessment of Different RNA Tetranucleotides from the DFT-D3 and Force Field Perspective. AB - Classical force field (FF) molecular dynamics (MD) simulations of RNA tetranucleotides have substantial problems in reproducing conformer populations indicated by NMR experiments. To provide more information about the possible sources of errors, we performed quantum mechanical (QM, TPSS-D3/def2-TZVP) and molecular mechanics (MM, AMBER parm99bsc0+chiOL3) calculations of different r(CCCC), r(GACC), and r(UUUU) conformers obtained from explicit solvent MD simulations. Solvent effects in the static QM and MM calculations were mimicked using implicit solvent models (COSMO and Poisson-Boltzmann, respectively). The comparison of QM and MM geometries and energies revealed that the two methodologies provide qualitatively consistent results in most of the cases. Even though we found some differences, these were insufficient to indicate any systematic corrections of the RNA FF terms that could improve the performance of classical MD in simulating tetranucleotides. On the basis of these findings, we inferred that the overpopulation of intercalated conformers in the MD simulations of RNA tetramers, which were not observed experimentally, might be predominantly caused by imbalanced water-solvent and water-water interactions. Apart from the large-scale QM calculations performed to assess the performance of the AMBER FF, a representative spectrum of faster QM methods was tested. PMID- 27681854 TI - Spatio-Temporal Variation in Age Structure and Abundance of the Endangered Snail Kite: Pooling across Regions Masks a Declining and Aging Population. AB - While variation in age structure over time and space has long been considered important for population dynamics and conservation, reliable estimates of such spatio-temporal variation in age structure have been elusive for wild vertebrate populations. This limitation has arisen because of problems of imperfect detection, the potential for temporary emigration impacting assessments of age structure, and limited information on age. However, identifying patterns in age structure is important for making reliable predictions of both short- and long term dynamics of populations of conservation concern. Using a multistate superpopulation estimator, we estimated region-specific abundance and age structure (the proportion of individuals within each age class) of a highly endangered population of snail kites for two separate regions in Florida over 17 years (1997-2013). We find that in the southern region of the snail kite-a region known to be critical for the long-term persistence of the species-the population has declined significantly since 1997, and during this time, it has increasingly become dominated by older snail kites (> 12 years old). In contrast, in the northern region-a region historically thought to serve primarily as drought refugia-the population has increased significantly since 2007 and age structure is more evenly distributed among age classes. Given that snail kites show senescence at approximately 13 years of age, where individuals suffer higher mortality rates and lower breeding rates, these results reveal an alarming trend for the southern region. Our work illustrates the importance of accounting for spatial structure when assessing changes in abundance and age distribution and the need for monitoring of age structure in imperiled species. PMID- 27681855 TI - Fabrication of Polydiacetylene Liposome Chemosensor with Enhanced Fluorescent Self-Amplification and Its Application for Selective Detection of Cationic Surfactants. AB - Polydiacetylene (PDA) materials have been adopted as one of the powerful conjugated polymers for sensing applications due to their unique optical properties. In this paper, we present a new PDA liposome-based sensor system with enhanced fluorescent self-amplification by tuning a fluorophore fluorescence emission. In this system, a 1,8-naphthalimide derivative employed as a highly fluorescent fluorophore was incorporated into a PDA supermolecule. During the formation of blue PDA liposomes, the fluorescence emission of the fluorophore can be directly quenched, while thermal-induced phase transition of PDA liposomes from blue to red can readily restore this fluorescence emission. These phenomena could be ascribed to the tunable Forster energy transfer between the excited fluorophore and PDA conjugated framework. To demonstrate the sensing performance of this newly prepared PDA liposome-based sensor, the sensor with fluorescent self-amplification was successfully applied for the detection of cationic surfactants (CS). The results show that the PDA liposomes displayed a distinct color change and fluorescence restoration in the presence of cationic surfactant species, and allowed detection of cationic surfactants with high sensitivity and selectivity. The limit of detection for target CS, such as cetyltrimethylammonium bromide (CTAB), can reach as low as 184 nM. Compared to the traditional methods based on colorimetric PDA liposomes, this newly fabricated PDA sensor system was superior for sensitivity. Thus, our findings offer an avenue for the design and development of new types of PDA sensors with enhanced sensitivity. PMID- 27681856 TI - Small Gold Nanoparticles Interfaced to Electrodes through Molecular Linkers: A Platform to Enhance Electron Transfer and Increase Electrochemically Active Surface Area. AB - For the smallest nanostructures (<5 nm), small changes in structure can lead to significant changes in properties and reactivity. In the case of nanoparticle (NP)-functionalized electrodes, NP structure and composition, and the nature of the NP-electrode interface have a strong influence upon electrochemical properties that are critical in applications such as amperometric sensing, photocatalysis and electrocatalysis. Existing methods to fabricate NP functionalized electrodes do not allow for precise control over all these variables, especially the NP-electrode interface, making it difficult to understand and predict how structural changes influence NP activity. We investigated the electrochemical properties of small (dcore < 2.5 nm) gold nanoparticles (AuNPs) on boron doped diamond electrodes using three different electrode fabrication techniques with varying degrees of nanoparticle-electrode interface definition. Two methods to attach AuNPs to the electrode through a covalently bound molecular linker were developed and compared to NP functionalized electrodes fabricated using solution deposition methods (drop casting and physiadsorption of a monolayer). In each case, a ferrocene redox probe was tethered to the AuNP surface to evaluate electron transfer through the AuNPs. The AuNPs that were molecularly interfaced with the electrode exhibited nearly ideal, reproducible electrochemical behavior with narrow redox peaks and small peak separations, whereas the solution deposited NPs had broader redox peaks with large peak separations. These data suggest that the molecular tether facilitates AuNP-mediated electron transfer. Interestingly, the molecularly tethered NPs also had significantly more electrochemically active surface area than the solution deposited NPs. The enhanced electrochemical behavior of the molecularly interfaced NPs demonstrates the significant influence of the interface on NP-mediated electron transfer and suggests that similar modified electrodes can serve as versatile platforms for studies and applications of nanoparticles. PMID- 27681857 TI - Biomechanical Analysis of the Individual Ligament Contributions to Syndesmotic Stability. AB - BACKGROUND: Biomechanical data and contributions to ankle joint stability have been previously reported for the individual distal tibiofibular ligaments. These results have not yet been validated based on recent anatomic descriptions or using current biomechanical testing devices. METHODS: Eight matched-pair, lower leg specimens were tested using a dynamic, biaxial testing machine. The proximal tibiofibular joint and the medial and lateral ankle ligaments were left intact. After fixation, specimens were preconditioned and then biomechanically tested following sequential cutting of the tibiofibular ligaments to assess the individual ligamentous contributions to syndesmotic stability. Matched paired specimens were randomly divided into 1 of 2 cutting sequences: (1) anterior-to posterior: intact, anterior inferior tibiofibular ligament (AITFL), interosseous tibiofibular ligament (ITFL), deep posterior inferior tibiofibular ligament (PITFL), superficial PITFL, and complete interosseous membrane; (2) posterior-to anterior: intact, superficial PITFL, deep PITFL, ITFL, AITFL, and complete interosseous membrane. While under a 750-N axial compressive load, the foot was rotated to 15 degrees of external rotation and 10 degrees of internal rotation for each sectioned state. Torque (Nm), rotational position (degrees), and 3 dimensional data were recorded continuously throughout testing. RESULTS: Testing of the intact ankle syndesmosis under simulated physiologic conditions revealed 4.3 degrees of fibular rotation in the axial plane and 3.3 mm of fibular translation in the sagittal plane. Significant increases in fibular sagittal translation and axial rotation were observed after syndesmotic injury, particularly after sectioning of the AITFL and superficial PITFL. Sequential sectioning of the syndesmotic ligaments resulted in significant reductions in resistance to both internal and external rotation. Isolated injuries to the AITFL resulted in the most substantial reduction of resistance to external rotation (average of 24%). However, resistance to internal rotation was not significantly diminished until the majority of the syndesmotic structures had been sectioned. CONCLUSION: The ligaments of the syndesmosis provide significant contributions to rotary stability of the distal tibiofibular joint within the physiologic range of motion. CLINICAL RELEVANCE: This study defined normal motion of the syndesmosis and the biomechanical consequences of injury. The degree of instability was increased with each additional injured structure; however, isolated injuries to the AITFL alone may lead to significant external rotary instability. PMID- 27681860 TI - Asymmetric Synthesis of Dipropionate Derivatives through Catalytic Hydrogenation of Enantioenriched E-Ketene Heterodimers. AB - A highly diastereoselective approach to dipropionate derivatives through Pd/C catalyzed hydrogenation of enantioenriched E-ketene heterodimers is described. Catalytic hydrogenation of the E-isomer of ketene heterodimer beta-lactones (12 examples) provides access to syn,anti-beta-lactones (dipropionate derivatives) bearing up to three stereogenic centers (dr up to 49:1), and with excellent transfer of chirality (ee up to >99%). PMID- 27681861 TI - Radiographic signs of pathology determining removal of an impacted mandibular third molar assessed in a panoramic image or CBCT. AB - OBJECTIVES: To (1) compare pathological findings related to the mandibular third molar in panoramic images (PAN) and CBCT; (2) estimate the frequency of removals if pathological findings were indicative; and (3) assess factors in PAN associated with resorption and marginal bone loss at the second molar as observed in CBCT. METHODS: 379 mandibular third molars were examined with PAN and CBCT. Four observers registered resorption and marginal bone loss at the second molar and increased periodontal space at the third molar in both imaging modalities. Agreement between PAN and CBCT, frequency of removals based on pathological findings in either of the two modalities and interobserver reproducibility was calculated. Logistic regression analyses assessed factors in PAN, which could predict marginal bone loss and resorption observed in CBCT. RESULTS: Agreement between PAN and CBCT: resorption 54-74%; marginal bone loss 66-85%; and increased periodontal space 92-97%. Removals based on CBCT and PAN: 58-71% and 36-65%. Interobserver percentage accordance and kappa values ranged from 57 to 98% and 0.10-0.91 for PAN and 61-97% and 0.22-0.78 for CBCT, respectively. Mesioangulated/horizontally positioned third molars were associated with marginal bone loss [odds ratio (OR) = 7.0-31.3; p < 0.001] and resorption (OR = 2.9-35.6; p < 0.001) in CBCT. Overprojection between the third and the second molars in PAN predicted resorption observed in CBCT (OR = 5.6-21.2; p < 0.001). CONCLUSIONS: Pathology associated with the third molar is more often observed in CBCT than in PAN. More third molars would be removed if pathological findings are based on CBCT. Mesioangulated/horizontally positioned third molars overprojecting the cervical/root part of the second molar in PAN are strongly associated with pathology observed in CBCT. PMID- 27681862 TI - Propofol Pharmacodynamics and Bispectral Index During Key Moments of Awake Craniotomy. AB - BACKGROUND: During awake craniotomy, the patient's language centers are identified by neurological testing requiring a fully awake and cooperative patient. Hence, anesthesia aims for an unconscious patient at the beginning and end of surgery but an awake and responsive patient in between. We investigated the plasma (Cplasma) and effect-site (Ceffect-site) propofol concentration as well as the related Bispectral Index (BIS) required for intraoperative return of consciousness and begin of neurological testing. MATERIALS AND METHODS: In 13 patients, arterial Cplasma were measured by high-pressure liquid chromatography and Ceffect-site was estimated based on the Marsh and Schnider pharmacokinetic/dynamic (pk/pd) models. The BIS, Cplasma and Ceffect-site were compared during the intraoperative awakening period at designated time points such as return of consciousness and start of the Boston Naming Test (neurological test). RESULTS: Return of consciousness occurred at a BIS of 77+/-7 (mean+/-SD) and a measured Cplasma of 1.2+/-0.4 MUg/mL. The Marsh model predicted a significantly (P<0.001) higher Cplasma of 1.9+/-0.4 ug/mL as compared with the Schnider model (Cplasma=1.4+/-0.4 ug/mL) at return of consciousness. Neurological testing was possible as soon as the BIS had increased to 92+/-6 and measured Cplasma had decreased to 0.8+/-0.3 ug/mL. This translated into a time delay of 23+/-12 minutes between return of consciousness and begin of neurological testing. At begin of neurological testing, Cplasma according to Marsh (Cplasma=1.3+/-0.5 ug/mL) was significantly (P=0.002) higher as compared with the Schnider model (Cplasma=1.0+/-0.4 ug/mL). CONCLUSIONS: To perform intraoperative neurological testing, patients are required to be fully awake with plasma propofol concentrations as low as 0.8 ug/mL. Following our clinical setup, the Schnider pk/pd model estimates propofol concentrations significantly more accurate as compared with the Marsh model at this neurologically crucial time point. PMID- 27681863 TI - Validation of the German patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAETM). AB - BACKGROUND: Integrating the patient's perspective has become an increasingly important component of adverse event reporting. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAETM). This instrument has been translated into German and linguistically validated; however, its quantitative measurement properties have not been evaluated. PATIENTS AND METHODS: A German language survey that included 31 PRO-CTCAE items, as well as the EORTC QLQ-C30 and the Oral Mucositis Daily Questionnaire (OMDQ), was distributed at 10 cancer treatment settings in Germany and Austria. Item quality was assessed by analysis of acceptability and comprehensibility. Reliability was evaluated by using Cronbach's' alpha and validity by principal components analysis (PCA), multitrait-multimethod matrix (MTMM) and known groups validity techniques. RESULTS: Of 660 surveys distributed to the study centres, 271 were returned (return rate 41%), and data from 262 were available for analysis. Participants' median age was 59.7 years, and 69.5% of the patients were female. Analysis of item quality supported the comprehensibility of the 31 PRO-CTCAE items. Reliability was very good; Cronbach's' alpha correlation coefficients were >0.9 for almost all item clusters. Construct validity of the PRO-CTCAE core item set was shown by identifying 10 conceptually meaningful item clusters via PCA. Moreover, construct validity was confirmed by the MTMM: monotrait-heteromethod comparison showed 100% high correlation, whereas heterotrait-monomethod comparison indicated 0% high correlation. Known groups validity was supported; PRO-CTCAE scores were significantly lower for those with impaired versus preserved health-related quality of life. CONCLUSION: A set of 31 items drawn from the German PRO-CTCAE item library demonstrated favourable measurement properties. These findings add to the body of evidence that PRO-CTCAE provides a rigorous method to capture patient self-reports of symptomatic toxicity for use in cancer clinical trials. PMID- 27681865 TI - Targeted next-generation sequencing identifies molecular subgroups in squamous cell carcinoma of the head and neck with distinct outcome after concurrent chemoradiation. AB - BACKGROUND: Based on epidemiological (HPV status, smoking habits) and clinical risk factors (T/N stage), three subgroups of patients suffering from locally advanced oropharyngeal carcinoma with significantly different outcome after concurrent chemoradiation (cCRTX) can be distinguished. Mutational profiling by targeted next-generation sequencing (NGS) might further improve risk stratification. PATIENTS AND METHODS: Patients with stage IV squamous cell carcinoma of the oropharynx and hypopharynx who had been enrolled in a randomized phase III trial (ARO-0401) comparing two regimens of cCRTX and from whom archival tumor specimens were available were included. The HPV status was determined by p16 immunostaining and detection of HPV DNA. Targeted NGS covering 45 genes frequently altered in squamous cell carcinoma of the head and neck (SCCHN) was applied for detection of non-synonymous somatic and germline mutations. Interference of mutational profiles with cCRTX efficacy was determined. RESULTS: The prognostic value of the 'Ang' risk model could be confirmed in the total biomarker study cohort (N = 175) as well as the patient subgroup for which mutational profiles could be established (N = 97). Mutations in genes involved in phosphoinositide 3-kinase (PI3K), receptor tyrosine kinase (RTK), and p53 signaling pathways were significantly enriched in the low- (N = 7), intermediate- (N = 20), and high-risk group (N = 70), respectively. Mutations in TP53 identified a subgroup of high-risk patients with dismal outcome after cCRTX. No prognostic relevance was observed for mutations in PI3K and RTK signaling pathways in the low- and intermediate-risk groups, respectively. Mutated NOTCH1 and two functional KDR germline variants (rs2305948, rs1870377) were associated with improved outcome in all risk groups. All genetic markers (TP53, NOTCH1, KDR) remained independent prognosticators of OS in the multivariate model. CONCLUSION: A potential of targeted NGS for risk classification of SCCHN cases beyond HPV status and clinical factors was demonstrated. PMID- 27681867 TI - Muscle activation comparisons between elastic and isoinertial resistance: A meta analysis. AB - BACKGROUND: Elastic resistance has been commonly used in the therapeutic and fitness setting; however, the ability of elastic resistance to overload and activate muscles has been questioned because of linear increase in elastic resistance as the device is elongated. The purpose of this meta-analysis was to examine the available literature on muscle activation associated with isoinertial and elastic resistance exercises, and to provide a quantitative summary comparing the two resistance training modes. METHODS: In a random-effects model, the Hedge's g effect size was used to calculate the biased corrected standardized mean difference between the elastic and isoinertial resistance activation of prime movers (agonist), antagonists, assistant movers and stabilizer muscles. FINDINGS: There was a lack of significant difference with the prime movers (effect size=-0.037, confidence interval: -0.202 to 0.128, p=0.660), antagonists (effect size=0.089, confidence interval: -0.112 to 0.290, p=0.385), synergists (effect size=-0.133, confidence interval: -0.342 to 0.076, p=0.213) and stabilizer (effect size=0.142, confidence interval: -0.006 to 0.289, p=0.060) muscle electromyography activity recorded during similar exercises using elastic and isoinertial resistance. INTERPRETATION: Elastic resistance provides similar prime mover, antagonist, assistant movers and stabilizer muscle activation as isoinertial resistance; contradicting the traditional criticism that the elastic band would not elicit comparable levels of muscle activation as isoinertial resistance exercise. Since development of muscle strength is closely related to the duration of muscle tension, relatively equal muscle adaptations could be expected following the two modes of training provided that equal external resistance is employed between the two exercises. LEVEL OF EVIDENCE: 2a. PMID- 27681864 TI - Metformin as an adjuvant treatment for cancer: a systematic review and meta analysis. AB - BACKGROUND: Metformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented. PATIENTS AND METHODS: We systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer. Studies were assessed for design and quality, and a meta analysis was conducted to quantify the adjuvant effect of metformin on recurrence free survival (RFS), overall survival (OS) and cancer-specific survival (CSS), to inform future trial design. RESULTS: Of 7670 articles screened, 27 eligible studies were identified comprising 24 178 participants, all enrolled in observational studies. In those with early-stage colorectal cancer, metformin use was associated with a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47-0.85; OS HR 0.69, CI 0.58-0.83; CSS HR 0.58, CI 0.39-0.86]. For men with early-stage prostate cancer, metformin was associated with significant, or borderline significant, benefits in all outcomes (RFS HR 0.83, CI 0.69-1.00; OS HR 0.82, CI 0.73-0.93; CSS HR 0.58, CI 0.37-0.93); however, there was significant heterogeneity between studies. The data suggest that prostate cancer patients treated with radical radiotherapy may benefit more from metformin (RFS HR 0.45, CI 0.29-0.70). In breast and urothelial cancer, no significant benefits were identified. Sufficient data were not available to conduct analyses on the impact of metformin dose and duration. CONCLUSIONS: Our findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical radiotherapy, and randomised, controlled trials which investigate dose and duration, alongside efficacy, are advocated. PMID- 27681868 TI - Religion and family planning. AB - Religion is embedded in the culture of all societies. It influences matters of morality, ideology and decision making, which concern every human being at some point in their life. Although the different religions often lack a united view on matters such contraception and abortion, there is sometimes some dogmatic overlap when general religious principles are subject to the influence of local customs. Immigration and population flow add further complexities to societal views on reproductive issues. For example, present day Europe has recently faced a dramatic increase in refugee influx, which raises questions about the health care of immigrants and the effects of cultural and religious differences on reproductive health. Religious beliefs on family planning in, for example, Christianity, Judaism, Islam and Hinduism have grown from different backgrounds and perspectives. Understanding these differences may result in more culturally competent delivery of care by health care providers. This paper presents the teachings of the most widespread religions in Europe with regard to contraception and reproduction. PMID- 27681866 TI - A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC). AB - BACKGROUND: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with Child-Pugh (CP) score <=7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for >=6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes. CONCLUSION: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP <=7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation. CLINICALTRIALSGOV IDENTIFIER: NCT01029418. PMID- 27681869 TI - Investigating the inhibitory effect of cyanide, phenol and 4-nitrophenol on the activated sludge process employed for the treatment of petroleum wastewater. AB - In this work, the inhibitory effect of cyanide, phenol and 4-nitrophenol on the activated sludge process was investigated. The inhibition of the aerobic oxidation of organic matter, nitrification and denitrification were examined in batch reactors by measuring the specific oxygen uptake rate (sOUR), the specific ammonium uptake rate (sAUR) and the specific nitrogen uptake rate (sNUR) respectively. The tested cyanide, phenol and 4-nitrophenol concentrations were 0.2-1.7 mg/L, 4.8-73.1 mg/L and 8.2-73.0 mg/L respectively. Cyanide was highly toxic as it significantly (>50%) inhibited the activity of autotrophic biomass, heterotrophic biomass under aerobic conditions and denitrifiers even at relatively low concentrations (1.0-1.7 mgCN-/L). The determination of the half maximum inhibitory concentration (IC50) confirmed this, since for cyanide IC50 values were very low for the examined bioprocesses (<1.5 mg/L). On the other hand, the IC50 values for phenol and 4-nitrophenol were much higher (>25 mg/L) for the tested bioprocesses since appreciable concentrations were required to accomplish significant inhibition. The autotrophic bacteria were more sensitive to phenol than the aerobic heterotrophs. The denitrifiers were found to be very resistant to phenol. PMID- 27681870 TI - On the design and assessment of regional air quality plans: The SHERPA approach. AB - Although significant progress has been made in Europe regarding air quality, problems still remain acute for some pollutants, notably NO2 and Particulate Matter (fine and coarse fractions) in specific regions/cities. One issue regarding air quality management is governance, i.e. the selection of appropriate and cost effective strategies over the area controlled by policy makers. In this work we present a new approach to integrated assessment modelling focusing on regional and urban aspects. One of the key added values is spatial flexibility, namely the possibility to assess the contributions from different regions to air quality at any given location. The SHERPA tool is shown to be particularly helpful in addressing the following tasks: source allocation, governance and the assessment of scenario impacts. Application of the methodology over the London area for yearly averaged PM2.5 concentrations demonstrates these features. Given that it is possible to use the SHERPA interface with other types of data, SHERPA can also be seen as a means to foster harmonization in the field of model evaluation. PMID- 27681871 TI - Indoor radon and thoron concentrations in some towns of central and South Serbia. AB - This study presents the results of indoor radon and thoron activity concentrations of some municipalities in central and south part of Serbia: Krusevac, Brus, Blace and Kursumlija. Measurements were carried out in 60 dwellings during the winter season. Passive discriminative radon-thoron detectors known as UFO detectors were used. The mean values of indoor radon and thoron concentrations were 82 Bq m-3 and 42 Bq m-3, respectively. Population-weighted mean values were 76 Bq m-3 and 40 Bq m-3, respectively. 26.7% of dwellings had radon concentration higher than 100 Bq m-3 (one location had even more than 300 Bq m-3). There are no statistically significant correlations of indoor radon and thoron concentrations neither with the period of house construction, nor with the existence of a basement. The results of this study represent the first step of investigating radon and thoron levels in these parts of Serbia and therefore could be the basis for creating a radon map. PMID- 27681872 TI - EU effect: Exporting emission standards for vehicles through the global market economy. AB - Emission data from EDGAR (Emissions Database for Global Atmospheric Research), rather than economic data, are used to estimate the effect of policies and of the global exports of policy-regulated goods, such as vehicles, on global emissions. The results clearly show that the adoption of emission standards for the road transport sector in the two main global markets (Europe and North America) has led to the global proliferation of emission-regulated vehicles through exports, regardless the domestic regulation in the country of destination. It is in fact more economically convenient for vehicle manufacturers to produce and sell a standard product to the widest possible market and in the greatest possible amounts. The EU effect (European Union effect) is introduced as a global counterpart to the California effect. The former is a direct consequence of the penetration of the EURO standards in the global markets by European and Japanese manufacturers, which effectively export the standard worldwide. We analyze the effect on PM2.5 emissions by comparing a scenario of non-EURO standards against the current estimates provided by EDGAR. We find that PM2.5 emissions were reduced by more than 60% since the 1990s worldwide. Similar investigations on other pollutants confirm the hypothesis that the combined effect of technological regulations and their diffusion through global markets can also produce a positive effect on the global environment. While we acknowledge the positive feedback, we also demonstrate that current efforts and standards will be totally insufficient should the passenger car fleets in emerging markets reach Western per capita figures. If emerging countries reach the per capita vehicle number of the USA and Europe under current technological conditions, then the world will suffer pre-1990 emission levels. PMID- 27681873 TI - Derivation of ecological criteria for copper in land-applied biosolids and biosolid-amended agricultural soils. AB - The difference in availability between soil metals added via biosolids and soluble salts was not taken into account in deriving the current land-applied biosolids standards. In the present study, a biosolids availability factor (BAF) approach was adopted to investigate the ecological thresholds for copper (Cu) in land-applied biosolids and biosolid-amended agricultural soils. First, the soil property-specific values of HC5add (the added hazardous concentration for 5% of species) for Cu2+ salt amended were collected with due attention to data for organisms and soils relevant to China. Second, a BAF representing the difference in availability between soil Cu added via biosolids and soluble salts was estimated based on long-term biosolid-amended soils, including soils from China. Third, biosolids Cu HC5input values (the input hazardous concentration for 5% of species of Cu from biosolids to soil) as a function of soil properties were derived using the BAF approach. The average potential availability of Cu in agricultural soils amended with biosolids accounted for 53% of that for the same soils spiked with same amount of soluble Cu salts and with a similar aging time. The cation exchange capacity was the main factor affecting the biosolids Cu HC5input values, while soil pH and organic carbon only explained 24.2 and 1.5% of the variation, respectively. The biosolids Cu HC5input values can be accurately predicted by regression models developed based on 2-3 soil properties with coefficients of determination (R2) of 0.889 and 0.945. Compared with model predicted biosolids Cu HC5input values, current standards (GB4284-84) are most likely to be less protective in acidic and neutral soil, but conservative in alkaline non-calcareous soil. Recommendations on ecological criteria for Cu in land-applied biosolids and biosolid-amended agriculture soils may be helpful to fill the gaps existing between science and regulations, and can be useful for Cu risk assessments in soils amended with biosolids. PMID- 27681875 TI - Neuropeptide Y Overexpressing Female and Male Mice Show Divergent Metabolic but Not Gut Microbial Responses to Prenatal Metformin Exposure. AB - BACKGROUND: Prenatal metformin exposure has been shown to improve the metabolic outcome in the offspring of high fat diet fed dams. However, if this is evident also in a genetic model of obesity and whether gut microbiota has a role, is not known. METHODS: The metabolic effects of prenatal metformin exposure were investigated in a genetic model of obesity, mice overexpressing neuropeptide Y in the sympathetic nervous system and in brain noradrenergic neurons (OE-NPYDbetaH). Metformin was given for 18 days to the mated female mice. Body weight, body composition, glucose tolerance and serum parameters of the offspring were investigated on regular diet from weaning and sequentially on western diet (at the age of 5-7 months). Gut microbiota composition was analysed by 16S rRNA sequencing at 10-11 weeks. RESULTS: In the male offspring, metformin exposure inhibited weight gain. Moreover, weight of white fat depots and serum insulin and lipids tended to be lower at 7 months. In contrast, in the female offspring, metformin exposure impaired glucose tolerance at 3 months, and subsequently increased body weight gain, fat mass and serum cholesterol. In the gut microbiota, a decline in Erysipelotrichaceae and Odoribacter was detected in the metformin exposed offspring. Furthermore, the abundance of Sutterella tended to be decreased and Parabacteroides increased. Gut microbiota composition of the metformin exposed male offspring correlated to their metabolic phenotype. CONCLUSION: Prenatal metformin exposure caused divergent metabolic phenotypes in the female and male offspring. Nevertheless, gut microbiota of metformin exposed offspring was similarly modified in both genders. PMID- 27681876 TI - Absence of TolC Impairs Biofilm Formation in Actinobacillus pleuropneumoniae by Reducing Initial Attachment. AB - Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a major cause of economic loss in swine industry worldwide. TolC, the key component of multidrug efflux pumps and type I secretion systems, has been well-studied as an exit duct for numerous substances in many Gram negative bacteria. By contrast, little is known on the role of TolC in biofilm formation. In this study, a DeltatolC mutant was used to examine the importance of TolC in biofilm formation of A. pleuropneumoniae. Surface attachment assays demonstrated the essential role of TolC in initial attachment of biofilm cells. The loss of TolC function altered surface hydrophobicity, and resulted in greatly reduced autoaggregation in DeltatolC. Using both enzymatic treatments and confocal microscopy, biofilm composition and architecture were characterized. When compared against the wild-type strain, the poly-beta-1, 6-N-acetyl-D glucosamine (PGA), an important biofilm matrix component of A. pleuropneumoniae, was significantly reduced at the initial attachment stage in DeltatolC. These results were confirmed by mRNA level using quantitative RT-PCR. Additionally, defective secretion systems in DeltatolC may also contribute to the deficiency in biofilm formation. Taken together, the current study demonstrated the importance of TolC in the initial biofilm formation stage in A. pleuropneumoniae. These findings could have important clinical implications in developing new treatments against biofilm-related infections by A. pleuropneumoniae. PMID- 27681879 TI - Microparticle and mitochondrial release during extended storage of different types of platelet concentrates. AB - On activation, platelets release vesicles called microparticles (MPs). MPs are heterogeneous with regard to the presence or absence of mitochondria. We quantified MPs in platelet concentrates (PCs) taking their mitochondrial content into account. Platelet-rich plasma (PRP), buffy coat (BC) and apheresis (AP) PCs were tested through 7 days of storage. A combination of flow cytometry and spanning-tree progression analysis of density-normalized events (SPADE) was used to determine MP and mitochondrial release during storage. All the PC biochemical parameters complied with transfusion standards at all times. Platelet activation markers increased during storage and were higher for PRP than other types of PCs. Concentrations of MPs and extracellular mitochondria interpreted by SPADE algorithm were significantly higher in PRP than other in PCs and were stable throughout storage. The mode of preparation, rather than storage duration, impacts the release of MPs and mitochondria in PCs. PMID- 27681880 TI - Variation in Weight and Obesity Comorbidities After Open Roux-en-Y Gastric Bypass by Health Insurance: Medicaid vs Medicare vs Private vs Self-Pay in 4225 Bariatric Outcomes Longitudinal Database Patients. PMID- 27681881 TI - My Vision for Universal, Quality, Affordable Health Care. PMID- 27681877 TI - Community acquired respiratory virus infections in cancer patients-Guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology. AB - BACKGROUND: Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly. METHODS: A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus. RESULTS: CRV infections in cancer patients may lead to pneumonia in approximately 30% of the cases, with an associated mortality of around 25%. For diagnosis of a CRV infection, combined nasal/throat swabs or washes/aspirates give the best results and nucleic acid amplification based-techniques (NAT) should be used to detect the pathogen. Hand hygiene, contact isolation and face masks have been shown to be of benefit as general infection management. Causal treatment can be given for influenza, using a neuraminidase inhibitor, and respiratory syncytial virus, using ribavirin in addition to intravenous immunoglobulins. Ribavirin has also been used to treat parainfluenza virus and human metapneumovirus, but data are inconclusive in this setting. Cidofovir is used to treat adenovirus pneumonitis. CONCLUSIONS: CRV infections may pose a vital threat to patients with underlying malignancy. This guideline provides information on diagnosis and treatment to improve the outcome. PMID- 27681878 TI - Joint Engagement and Early Language in Young Children With Fragile X Syndrome. AB - Purpose: In this study, we examine joint engagement (JE) in young children with fragile X syndrome (FXS) and its relationship to language abilities and autism spectrum disorder symptomatology at 24 to 36 months (toddler period) and 59 to 68 months (child period). Method: Participants were 28 children with FXS (24 boys, four girls) and their mothers. Videotaped home observations were conducted during the toddler period and coded for JE. Language abilities were measured at both ages from a developmental assessment, a functional measure, and from a language sample. The Childhood Autism Rating Scale (Schopler, Reichler, & Renner, 1988) was completed at both ages. Results: Children with FXS spent more time in supported JE than in coordinated JE. Using a weighted JE variable, we found that children with FXS who had higher weighted JE scores also had more advanced expressive language skills at both the toddler and child periods. Weighted JE was negatively related to autism symptomatology in the toddler period. Conclusion: This study provides evidence that children with FXS who use more JE also have more advanced expressive language skills in early development. Therefore, existing early interventions that target JE behaviors may be effective for promoting language, social communication, and social interaction in this population. PMID- 27681883 TI - Changes in quality of life in patients with acromegaly after surgical remission - A prospective study using SF-36 questionnaire. AB - Patients with acromegaly have a compromised quality of life (QOL). Modern surgical techniques have improved the surgical cure rate. However, there are no prospective studies reporting postoperative changes in QOL among patients cured solely by surgery. The aim of the present study was to determine the effect of surgery on QOL using the 36-item short form health survey (SF-36) questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS). Included in this prospective cohort were 41 patients with acromegaly who underwent surgery alone and achieved postoperative normalization of insulin-like growth factor-1. All participants completed the SF-36 preoperatively and 1 year postoperatively. Preoperatively, RCS and 4 subscale scores (role physical, social functioning, role emotional, mental health) were below the set standards for the normal population. Postoperatively, the PCS and RCS scores did not change significantly, but the MCS score improved significantly (from 48.1 +/- 11.3 to 51.7 +/- 8.9, p=0.03). Further we compared the QOL of 26 patients whose nadir GH level was < 0.4 MUg/L during postoperative oral glucose tolerance testing (complete remission group) with that of 15 patients whose nadir GH level was >= 0.4 MUg/L (partial remission group). There were no significant differences between these groups in terms of PCS, MCS, RCS, or any subscale scores. In conclusion, surgical remission mostly improved the participants' mental condition. There was no difference in QOL between patients who achieved the new remission criteria and those who did not. PMID- 27681882 TI - Immunomodulatory effects of nicotine on interleukin 1beta activated human astrocytes and the role of cyclooxygenase 2 in the underlying mechanism. AB - BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) primarily functions through acetylcholine (ACh)-alpha7 nicotinic acetylcholine receptor (alpha7nAChR) interaction on macrophages to control peripheral inflammation. Interestingly, ACh can also bind alpha7nAChRs on microglia resulting in neuroprotective effects. However, ACh effects on astrocytes remain elusive. Here, we investigated the effects of nicotine, an ACh receptor agonist, on the cytokine and cholinesterase production of immunocompetent human astrocytes stimulated with interleukin 1beta (IL-1beta) in vitro. In addition, the potential involvement of prostaglandins as mediators of nicotine was studied using cyclooxygenase 2 (COX-2) inhibition. METHODS: Cultured human fetal astrocytes were stimulated with human recombinant IL-1beta and treated simultaneously with nicotine at different concentrations (1, 10, and 100 MUM). Cell supernatants were collected for cytokine and cholinesterase profiling using ELISA and MesoScale multiplex assay. alpha7nAChR expression on activated human astrocytes was studied using immunofluorescence. For the COX-2 inhibition studies, enzyme activity was inhibited using NS-398. One way ANOVA was used to perform statistical analyses. RESULTS: Nicotine treatment dose dependently limits the production of critical proinflammatory cytokines such as IL-6 (60.5 +/- 3.3, %inhibition), IL-1beta (42.4 +/- 1.7, %inhibition), and TNF-alpha (68.9 +/- 7.7, %inhibition) by activated human astrocytes. Interestingly, it also inhibits IL-8 chemokine (31.4 +/- 8.5, %inhibition), IL-13 (34.243 +/- 4.9, %inhibition), and butyrylcholinesterase (20.8 +/- 2.8, %inhibition) production at 100 MUM. Expression of alpha7nAChR was detected on the activated human astrocytes. Importantly, nicotine's inhibitory effect on IL-6 production was reversed with the specific COX-2 inhibitor NS-398. CONCLUSIONS: Activation of the cholinergic system through alpha7nAChR agonists has been known to suppress inflammation both in the CNS and periphery. In the CNS, earlier experimental data shows that cholinergic activation through nicotine inhibits microglial activation and proinflammatory cytokine release. Here, we report similar anti-inflammatory effects of cholinergic activation on human astrocytes, at least partly mediated through the COX-2 pathway. These results confirm the potential for cholinergic neuroprotection, which is looked upon as a promising therapy for neuroinflammation as well as neurodegenerative diseases and stroke. Our data implicates an important role for the prostaglandin system in cholinergic regulatory effects. PMID- 27681884 TI - Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]. AB - Steroid hormones are mainly produced in adrenal glands and gonads. Because steroid hormones play vital roles in various physiological processes, replacement of deficient steroid hormones by hormone replacement therapy (HRT) is necessary for patients with adrenal and gonadal failure. In addition to HRT, tissue regeneration using stem cells is predicted to provide novel therapy. Among various stem cell types, mesenchymal stem cells can be differentiated into steroidogenic cells following ectopic expression of nuclear receptor (NR) 5A subfamily proteins, steroidogenic factor-1 (also known as adrenal 4 binding protein) and liver receptor homolog-1, with the aid of cAMP signaling. Conversely, these approaches cannot be applied to pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, because of poor survival following cytotoxic expression of NR5A subfamily proteins. However, if pluripotent stem cells are first differentiated through mesenchymal lineage, they can also be differentiated into steroidogenic cells via NR5A subfamily protein expression. This approach offers a potential suitable cells for future regenerative medicine and gene therapy for diseases caused by steroidogenesis deficiencies. It represents a powerful tool to investigate the molecular mechanisms involved in steroidogenesis. This article highlights our own and current research on the induction of steroidogenic cells from various stem cells. We also discuss the future direction of their clinical application. PMID- 27681874 TI - Functional characterization of AMP-activated protein kinase signaling in tumorigenesis. AB - AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer. PMID- 27681885 TI - Prevalence and associated factors of vernal keratoconjunctivitis among children in Gondar city, Northwest Ethiopia. AB - BACKGROUND: Vernal keratoconjunctivitis (VKC) is a common cause of ocular morbidity in children in warm dry climates such as Sub-Saharan Africa and accounts for about 3 % of serious ophthalmic cases in tropical countries. The purpose of this study was to assess the prevalence and associated factors of vernal keratoconjunctivitis among children living in Gondar City, Ethiopia. METHODS: A Cross Sectional Design study was carried out in 737 children under the age of 18 years in Gondar City from April to May 2015. Basic ophthalmic examination was performed using a 3x magnifying loop and torch light and a pretested and structured questionnaire was completed. The association between vernal keratoconjunctivitis and factors such as socio-economic, demographic, and environmental status, and history of allergic disease in affected children and their family members was examined using logistic regression multivariate analysis. RESULTS: The prevalence of vernal keratoconjunctivitis was 5.8 % (95 % CI: 4.14, 7.53) (43/737) and mixed type VKC was the most frequent form which was found in 35 out of 43 cases (81.4 %). The following were positively associated with vernal keratoconjunctivitis: use of kerosene/firewood for cooking (AOR = 6.25 (95 % CI: 1.61, 25)), child dust exposure (AOR = 10.0 (95 % CI: 4.16, 20.0)), child history of non-ocular allergic diseases (AOR = 4.0 (95 % CI: 1.92, 8.33)), family history of non-ocular allergic diseases (AOR = 3.57(95 % CI: 1.39, 9.09). CONCLUSION: There is a high prevalence of vernal keratoconjunctivitis in this region. The use of kerosene/firewood for cooking, child dust exposure, and non-ocular allergic disease in the child or their family were statistically significant risk factors for vernal keratoconjunctivitis. PMID- 27681886 TI - Collaboration Needed: Pain Care and Opioid Abuse. PMID- 27681887 TI - Controlling Marangoni-induced instabilities in spin-cast polymer films: How to prepare uniform films. AB - In both research and industrial settings spincoating is extensively used to prepare highly uniform thin polymer films. However, under certain conditions, spincoating results in films with non-uniform surface morphologies. Although the spincoating process has been extensively studied, the origin of these morphologies is not fully understood and the formation of non-uniform spin-cast films remains a practical problem. Here we report on experiments demonstrating that the formation of surface instabilities during spincoating is dependent on temperature. Our results suggest that non-uniform spin-cast films form as a result of the Marangoni effect, which describes flow due to surface tension gradients. We find that both the wavelength and amplitude of the pattern increase with temperature. Finally, and most important from a practical viewpoint, the non uniformities in the film thickness can be entirely avoided simply by lowering the spin coating temperature. PMID- 27681888 TI - A Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Orally Administered Des-Aspartate Angiotensin I in Healthy Subjects. AB - Des-aspartate-angiotensin I (DAA-I) is an endogenous angiotensin peptide and a prototype angiotensin receptor agonist (ARA). It acts on the angiotensin AT1 receptor and antagonises the deleterious actions of angiotensin II. DAA-I attenuates animal models of human disease in which angiotensin II has been implicated, such as cardiac hypertrophy, neointima formation, arteriosclerosis, renal failure, post-infarction injuries, diabetes, viral infection, chemical induced inflammation, heat stroke, cancer, and gamma radiation lethality. DAA-I crosses Caco-2 cells and is effective at sub-nanomolar concentrations. These two properties are responsible for its oral efficacy. A single dose-escalation study was conducted to evaluate the safety, tolerability and pharmacokinetics of orally administered DAA-I in 18 healthy subjects. DAA-I was safe and well tolerated by the subjects, who were administered either 0.08, 0.70 or 1.50 mg/kg of the compound. The heart rate and systolic and diastolic blood pressures determined at each post-dose measurement remained within the clinically acceptable range. Across all cohorts, DAA-I had no substantial effect on blood pressures compared with placebo. Electrocardiographs (ECGs) were normal, and none of the subjects complained of chest discomfort. All clinical laboratory tests obtained before and after DAA-I and placebo treatment were normal. Pharmacokinetic analysis over a 12 h period following DAA-I administration did not show any increase of its level beyond basal concentration. This is in line with studies showing that intravenously administered DAA-I is rapidly metabolized and has a short half life. We postulate that, during its short systemic sojourn, DAA-I exerts its actions via biased agonism on the angiotensin AT1 receptor.The ClinicalTrial.gov assignment number for this study is NCT02666196. PMID- 27681890 TI - Cardiac monitoring for detection of atrial fibrillation after TIA: A systematic review and meta-analysis. AB - Background and purpose The detection rate of atrial fibrillation has not been studied specifically in transient ischemic attack (TIA) patients although extrapolation from ischemic stroke may be inadequate. We conducted a systematic review and meta-analysis to determine the rate of newly diagnosed atrial fibrillation using different methods of ECG monitoring in TIA. Methods A comprehensive literature search was performed following a pre-specified protocol the PRISMA statement. Prospective observational studies and randomized controlled trials were considered that included TIA patients who underwent cardiac monitoring for >12 h. Primary outcome was frequency of detection of atrial fibrillation >=30 s. Analyses of subgroups and of duration and type of monitoring were performed. Results Seventeen studies enrolling 1163 patients were included. The pooled atrial fibrillation detection rate for all methods was 4% (95% CI: 2 7%). Yield of monitoring was higher in selected (higher age, more extensive testing for arrhythmias before enrolment, or presumed cardioembolic/cryptogenic cause) than in unselected cohorts (7% vs 3%). Pooled mean atrial fibrillation detection rates rose with duration of monitoring: 4% (24 h), 5% (24 h to 7 days) and 6% (>7 days), respectively. Yield of non-invasive was significantly lower than that of invasive monitoring (4% vs. 11%). Significant heterogeneity was observed among studies (I2=60.61%). Conclusion This first meta-analysis of atrial fibrillation detection in TIA patients finds a lower atrial fibrillation detection rate in TIA than reported for IS and TIA cohorts in previous meta analyses. Prospective studies are needed to determine actual prevalence of atrial fibrillation and optimal diagnostic procedure for atrial fibrillation detection in TIA. PMID- 27681889 TI - Cognitive control exertion leads to reductions in peak power output and [Formula: see text] as well as increased perceived exertion on a graded exercise test to exhaustion. AB - We investigated effects of a brief (10.5 min) cognitively demanding task on graded exercise test performance. Untrained, university students (N = 15) completed two graded exercise tests in counterbalanced, randomised order. One test was preceded by restful viewing of a documentary video (control); the other by a stop-signal task. Cardiorespiratory functions and perceived exertion were monitored during exercise. Peak power output (W) was lower following the stop signal task (M = 240.03, SD = 53.37) compared to control (M = 246.03, SD = 52.60), P = 0.002, etaP2 = 0.493, as was [Formula: see text] (P = 0.042, Cohen's d = 0.55). Perceived exertion was significantly higher at 50% (d = 0.77) and 75% (d = 0.83) of iso-time following the cognitive task (Ps <= 0.01). Results are consistent with research showing negative carryover effects of cognitively demanding tasks on whole-body endurance performance. Results also support the psychobiological model of exercise as performance of the cognitive task did not affect perceived exertion when exercise task demands were lower, but lead to greater perceived exertion and earlier withdrawal of effort at higher levels of exercise task demand. Findings have implications for understanding psychological determinants of exercise performance and conditions that may lead to underestimation of [Formula: see text]. PMID- 27681891 TI - Primary stroke prevention needs overhaul. AB - There is compelling evidence from the Global Burden of Disease (GBD) Study that the burden of stroke and cardiovascular disease (CVD) has been increasing fast over the last two and half decades. These deficiencies are further highlighted by significant gender and ethnic disparities, and a trend towards more strokes in younger people. This suggests very strongly that currently used primary stroke and CVD prevention measures, which include high-risk (screening of the population for absolute CVD risk) and population-wide strategies, are not sufficiently effective. Identifying the causes of the failure in primary stroke and CVD prevention on individual and population levels and the most promising strategies to improve the situation is the first step in combating these leading causes of disease burden in the world. PMID- 27681892 TI - Erratum to: Surgical accuracy in high tibial osteotomy: coronal equivalence of computer navigation and gap measurement. PMID- 27681893 TI - Arthroscopic suture bridge fixation technique with multiple crossover ties for posterior cruciate ligament tibial avulsion fracture. AB - PURPOSE: This study examined the clinical outcomes of a newly developed technique, arthroscopic suture bridge fixation with crossover ties of PCL tibial avulsion fracture using two tibial tunnels and a posterior trans-septal portal. METHODS: Records were reviewed of 18 patients (median age 33.5 years, range 13-55 years) with PCL tibial avulsion fractures treated with an arthroscopic suture bridge technique. Knee function before surgery and at last follow-up was evaluated by Lysholm and Tegner scores. A KT-2000 arthrometer was used to evaluate knee stability, and fracture union was assessed by plain radiographs. RESULTS: Mean postoperative Lysholm (P < 0.001) and Tegner (P = 0.011) scores showed significant improvements compared with preoperative scores. Arthrometry showed that the mean side-to-side difference improved significantly, from 7.8 +/- 0.8 mm preoperatively to 3 +/- 1.2 mm postoperatively (P = 0.012). Radiographic evaluation showed solid union at the fracture site in all 18 patients at last follow-up. CONCLUSION: This new arthroscopic double-tunnel pull-out suture bridge fixation with multiple crossover ties and posterior trans-septal technique for PCL tibial avulsion fracture yielded good clinico-radiological outcomes, including satisfactory stability and fracture site healing. This technique can be a useful treatment option for PCL tibial avulsion fracture even with small comminuted fracture due to compression by the unique crossover configuration mesh of multiple fixation sutures. LEVEL OF EVIDENCE: IV. PMID- 27681894 TI - Erratum to: Clinical characteristics and outcomes of spontaneous bacterial peritonitis caused by Enterobacter species versus Escherichia coli: a matched case-control study. PMID- 27681896 TI - In Silico Analysis of a Novel Plasmid from the Coral Pathogen Vibrio coralliilyticus Reveals Two Potential "Ecological Islands". AB - As virulence often correlates with the presence of plasmid replicons in several Vibrio spp., this study investigated whether non-chromosomal DNA could be found in the coral pathogen, Vibrio coralliilyticus BAA-450. A circular plasmid, 26,631 bp in size, was identified. DNA sequence analysis indicated that the plasmid contained 30 open reading frames, six tRNA genes, 12 inverted repeats, three direct repeats and presented no continuous sequence identity to other replicons within the database. Consequently, these findings indicate that this is a novel, previously unidentified, plasmid. Two putative "ecological islands" were also identified and are predicted to encode for various factors that would facilitate growth and survival under different ecological conditions. In addition, two open reading frames may encode proteins that contribute to the pathogenicity of the organism. Functional cooperativity is also indicated between several plasmid- and chromosomally-encoded proteins, which, in a single instance, would allow a fully functioning nutrient uptake system to be established. PMID- 27681895 TI - Influence of pH Regulation Mode in Glucose Fermentation on Product Selection and Process Stability. AB - Mixed culture anaerobic fermentation generates a wide range of products from simple sugars, and is potentially an effective process for producing renewable commodity chemicals. However it is difficult to predict product spectrum, and to control the process. One of the key control handles is pH, but the response is commonly dependent on culture history. In this work, we assess the impact of pH regulation mode on the product spectrum. Two regulation modes were applied: in the first, pH was adjusted from 4.5 to 8.5 in progressive steps of 0.5 and in the second, covered the same pH range, but the pH was reset to 5.5 before each change. Acetate, butyrate, and ethanol were produced throughout all pH ranges, but there was a shift from butyrate at pH < 6.5 to ethanol at pH > 6.5, as well as a strong and consistent shift from hydrogen to formate as pH increased. Microbial analysis indicated that progressive pH resulted in dominance by Klebsiella, while reset pH resulted in a bias towards Clostridium spp., particularly at low pH, with higher variance in community between different pH levels. Reset pH was more responsive to changes in pH, and analysis of Gibbs free energy indicated that the reset pH experiments operated closer to thermodynamic equilibrium, particularly with respect to the formate/hydrogen balance. This may indicate that periodically resetting pH conforms better to thermodynamic expectations. PMID- 27681897 TI - Microbial Biofilm Community Variation in Flowing Habitats: Potential Utility as Bioindicators of Postmortem Submersion Intervals. AB - Biofilms are a ubiquitous formation of microbial communities found on surfaces in aqueous environments. These structures have been investigated as biomonitoring indicators for stream heath, and here were used for the potential use in forensic sciences. Biofilm successional development has been proposed as a method to determine the postmortem submersion interval (PMSI) of remains because there are no standard methods for estimating the PMSI and biofilms are ubiquitous in aquatic habitats. We sought to compare the development of epinecrotic (biofilms on Sus scrofa domesticus carcasses) and epilithic (biofilms on unglazed ceramic tiles) communities in two small streams using bacterial automated ribosomal intergenic spacer analysis. Epinecrotic communities were significantly different from epilithic communities even though environmental factors associated with each stream location also had a significant influence on biofilm structure. All communities at both locations exhibited significant succession suggesting that changing communities throughout time is a general characteristic of stream biofilm communities. The implications resulting from this work are that epinecrotic communities have distinctive shifts at the first and second weeks, and therefore the potential to be used in forensic applications by associating successional changes with submersion time to estimate a PMSI. The influence of environmental factors, however, indicates the lack of a successional pattern with the same organisms and a focus on functional diversity may be more applicable in a forensic context. PMID- 27681898 TI - Phage Inactivation of Listeria monocytogenes on San Daniele Dry-Cured Ham and Elimination of Biofilms from Equipment and Working Environments. AB - The anti-listerial activity of generally recognized as safe (GRAS) bacteriophage Listex P100 (phage P100) was demonstrated in broths and on the surface of slices of dry-cured ham against 5 strains or serotypes (i.e., Scott A, 1/2a, 1/2b, and 4b) of Listeria monocytogenes. In a broth model system, phage P100 at a concentration equal to or greater than 7 log PFU/mL completely inhibited 2 log CFU/cm2 or 3 log CFU/cm2 of L. monocytogenes growth at 30 degrees C. The temperature (4, 10, 20 degrees C) seemed to influence P100 activity; the best results were obtained at 4 degrees C. On dry-cured ham slices, a P100 concentration ranging from 5 to 8 log PFU/cm2 was required to obtain a significant reduction in L. monocytogenes. At 4, 10, and 20 degrees C, an inoculum of 8 log PFU/cm2 was required to completely eliminate 2 log L. monocytogenes/cm2 and to reach the absence in 25 g product according to USA food law. Conversely, it was impossible to completely eradicate L. monocytogenes with an inoculum of approximately of 3.0 and 4.0 log CFU/cm2 and with a P100 inoculum ranging from 1 to 7 log PFU/cm2. P100 remained stable on dry-cured ham slices over a 14-day storage period, with only a marginal loss of 0.2 log PFU/cm2 from an initial phage treatment of approximately 8 log PFU/cm2. Moreover, phage P100 eliminated free L. monocytogenes cells and biofilms on the machinery surfaces used for dry-cured ham production. These findings demonstrate that the GRAS bacteriophage Listex P100 at level of 8 log PFU/cm2 is listericidal and useful for reducing the L. monocytogenes concentration or eradicating the bacteria from dry-cured ham. PMID- 27681899 TI - Low Substrate Loading Limits Methanogenesis and Leads to High Coulombic Efficiency in Bioelectrochemical Systems. AB - A crucial aspect for the application of bioelectrochemical systems (BESs) as a wastewater treatment technology is the efficient oxidation of complex substrates by the bioanode, which is reflected in high Coulombic efficiency (CE). To achieve high CE, it is essential to give a competitive advantage to electrogens over methanogens. Factors that affect CE in bioanodes are, amongst others, the type of wastewater, anode potential, substrate concentration and pH. In this paper, we focus on acetate as a substrate and analyze the competition between methanogens and electrogens from a thermodynamic and kinetic point of view. We reviewed experimental data from earlier studies and propose that low substrate loading in combination with a sufficiently high anode overpotential plays a key-role in achieving high CE. Low substrate loading is a proven strategy against methanogenic activity in large-scale reactors for sulfate reduction. The combination of low substrate loading with sufficiently high overpotential is essential because it results in favorable growth kinetics of electrogens compared to methanogens. To achieve high current density in combination with low substrate concentrations, it is essential to have a high specific anode surface area. New reactor designs with these features are essential for BESs to be successful in wastewater treatment in the future. PMID- 27681901 TI - Metagenomic Analyses Reveal That Energy Transfer Gene Abundances Can Predict the Syntrophic Potential of Environmental Microbial Communities. AB - Hydrocarbon compounds can be biodegraded by anaerobic microorganisms to form methane through an energetically interdependent metabolic process known as syntrophy. The microorganisms that perform this process as well as the energy transfer mechanisms involved are difficult to study and thus are still poorly understood, especially on an environmental scale. Here, metagenomic data was analyzed for specific clusters of orthologous groups (COGs) related to key energy transfer genes thus far identified in syntrophic bacteria, and principal component analysis was used in order to determine whether potentially syntrophic environments could be distinguished using these syntroph related COGs as opposed to universally present COGs. We found that COGs related to hydrogenase and formate dehydrogenase genes were able to distinguish known syntrophic consortia and environments with the potential for syntrophy from non-syntrophic environments, indicating that these COGs could be used as a tool to identify syntrophic hydrocarbon biodegrading environments using metagenomic data. PMID- 27681900 TI - Molecular Ecology of Hypersaline Microbial Mats: Current Insights and New Directions. AB - Microbial mats are unique geobiological ecosystems that form as a result of complex communities of microorganisms interacting with each other and their physical environment. Both the microorganisms present and the network of metabolic interactions govern ecosystem function therein. These systems are often found in a range of extreme environments, and those found in elevated salinity have been particularly well studied. The purpose of this review is to briefly describe the molecular ecology of select model hypersaline mat systems (Guerrero Negro, Shark Bay, S'Avall, and Kiritimati Atoll), and any potentially modulating effects caused by salinity to community structure. In addition, we discuss several emerging issues in the field (linking function to newly discovered phyla and microbial dark matter), which illustrate the changing paradigm that is seen as technology has rapidly advanced in the study of these extreme and evolutionally significant ecosystems. PMID- 27681904 TI - Aspergillus oryzae-Saccharomyces cerevisiae Consortium Allows Bio-Hybrid Fuel Cell to Run on Complex Carbohydrates. AB - Consortia of Aspergillus oryzae and Saccharomyces cerevisiae are examined for their abilities to turn complex carbohydrates into ethanol. To understand the interactions between microorganisms in consortia, Fourier-transform infrared spectroscopy is used to follow the concentrations of various metabolites such as sugars (e.g., glucose, maltose), longer chain carbohydrates, and ethanol to optimize consortia conditions for the production of ethanol. It is shown that with proper design A. oryzae can digest food waste simulants into soluble sugars that S. cerevisiae can ferment into ethanol. Depending on the substrate and conditions used, concentrations of 13% ethanol were achieved in 10 days. It is further shown that a direct alcohol fuel cell (FC) can be coupled with these A. oryzae-enabled S. cerevisiae fermentations using a reverse osmosis membrane. This "bio-hybrid FC" continually extracted ethanol from an ongoing consortium, enhancing ethanol production and allowing the bio-hybrid FC to run for at least one week. Obtained bio-hybrid FC currents were comparable to those from pure ethanol-water mixtures, using the same FC. The A. oryzae-S. cerevisiae consortium, coupled to a bio-hybrid FC, converted food waste simulants into electricity without any pre- or post-processing. PMID- 27681902 TI - Extremophiles in an Antarctic Marine Ecosystem. AB - Recent attempts to explore marine microbial diversity and the global marine microbiome have indicated a large proportion of previously unknown diversity. However, sequencing alone does not tell the whole story, as it relies heavily upon information that is already contained within sequence databases. In addition, microorganisms have been shown to present small-to-large scale biogeographical patterns worldwide, potentially making regional combinations of selection pressures unique. Here, we focus on the extremophile community in the boundary region located between the Polar Front and the Southern Antarctic Circumpolar Current in the Southern Ocean, to explore the potential of metagenomic approaches as a tool for bioprospecting in the search for novel functional activity based on targeted sampling efforts. We assessed the microbial composition and diversity from a region north of the current limit for winter sea ice, north of the Southern Antarctic Circumpolar Front (SACCF) but south of the Polar Front. Although, most of the more frequently encountered sequences were derived from common marine microorganisms, within these dominant groups, we found a proportion of genes related to secondary metabolism of potential interest in bioprospecting. Extremophiles were rare by comparison but belonged to a range of genera. Hence, they represented interesting targets from which to identify rare or novel functions. Ultimately, future shifts in environmental conditions favoring more cosmopolitan groups could have an unpredictable effect on microbial diversity and function in the Southern Ocean, perhaps excluding the rarer extremophiles. PMID- 27681905 TI - The Opportunity for High-Performance Biomaterials from Methane. AB - Polyhydroxyalkanoate (PHA) biopolymers are widely recognised as outstanding candidates to replace conventional petroleum-derived polymers. Their mechanical properties are good and can be tailored through copolymer composition, they are biodegradable, and unlike many alternatives, they do not rely on oil-based feedstocks. Further, they are the only commodity polymer that can be synthesised intracellularly, ensuring stereoregularity and high molecular weight. However, despite offering enormous potential for many years, they are still not making a significant impact. This is broadly because commercial uptake has been limited by variable performance (inconsistent polymer properties) and high production costs of the raw polymer. Additionally, the main type of PHA produced naturally is poly 3-hydroxybutyrate (PHB), which has limited scope due to its brittle nature and low thermal stability, as well as its tendency to embrittle over time. Production cost is strongly impacted by the type of the feedstock used. In this article we consider: the production of PHAs from methanotrophs using methane as a cost effective substrate; the use of mixed cultures, as opposed to pure strains; and strategies to generate a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer (PHBV), which has more desirable qualities such as toughness and elasticity. PMID- 27681906 TI - Staphylococcus aureus in Animals and Food: Methicillin Resistance, Prevalence and Population Structure. A Review in the African Continent. AB - The interest about Staphylococcus aureus (S. aureus) and methicillin resistant S. aureus (MRSA) in livestock, and domestic and wild animals has significantly increased. The spread of different clonal complexes related to livestock animals, mainly CC398, and the recent description of the new mecC gene, make it necessary to know more about the epidemiology and population structure of this microorganism all over the world. Nowadays, there are several descriptions about the presence of S. aureus and/or MRSA in different animal species (dogs, sheep, donkeys, bats, pigs, and monkeys), and in food of animal origin in African countries. In this continent, there is a high diversity of ethnicities, cultures or religions, as well as a high number of wild animal species and close contact between humans and animals, which can have a relevant impact in the epidemiology of this microorganism. This review shows that some clonal lineages associated with humans (CC1, CC15, CC72, CC80, CC101, and CC152) and animals (CC398, CC130 and CC133) are present in this continent in animal isolates, although the mecC gene has not been detected yet. However, available studies are limited to a few countries, very often with incomplete information, and many more studies are necessary to cover a larger number of African countries. PMID- 27681907 TI - Carbapenem Resistance in Gram-Negative Bacteria: The Not-So-Little Problem in the Little Red Dot. AB - Singapore is an international travel and medical hub and faces a genuine threat for import and dissemination of bacteria with broad-spectrum resistance. In this review, we described the current landscape and management of carbapenem resistance in Gram-negative bacteria (GNB) in Singapore. Notably, the number of carbapenem-resistant Enterobacteriaceae has exponentially increased in the past two years. Resistance is largely mediated by a variety of mechanisms. Polymyxin resistance has also emerged. Interestingly, two Escherichia coli isolates with plasmid-mediated mcr-1 genes have been detected. Evidently, surveillance and infection control becomes critical in the local setting where resistance is commonly related to plasmid-mediated mechanisms, such as carbapenemases. Combination antibiotic therapy has been proposed as a last-resort strategy in the treatment of extensively drug-resistant (XDR) GNB infections, and is widely adopted in Singapore. The diversity of carbapenemases encountered, however, presents complexities in both carbapenemase detection and the selection of optimal antibiotic combinations. One unique strategy introduced in Singapore is a prospective in vitro combination testing service, which aids physicians in the selection of individualized combinations. The outcome of this treatment strategy has been promising. Unlike countries with a predominant carbapenemase type, Singapore has to adopt management strategies which accounts for diversity in resistance mechanisms. PMID- 27681909 TI - Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota. AB - As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D). Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders. PMID- 27681911 TI - Process Recovery after CaO Addition Due to Granule Formation in a CSTR Co Digester-A Tool to Influence the Composition of the Microbial Community and Stabilize the Process? AB - The composition, structure and function of granules formed during process recovery with calcium oxide in a laboratory-scale fermenter fed with sewage sludge and rapeseed oil were studied. In the course of over-acidification and successful process recovery, only minor changes were observed in the bacterial community of the digestate, while granules appeared during recovery. Fluorescence microscopic analysis of the granules showed a close spatial relationship between calcium and oil and/or long chain fatty acids. This finding further substantiated the hypothesis that calcium precipitated with carbon of organic origin and reduced the negative effects of overloading with oil. Furthermore, the enrichment of phosphate minerals in the granules was shown, and molecular biological analyses detected polyphosphate-accumulating organisms as well as methanogenic archaea in the core. Organisms related to Methanoculleus receptaculi were detected in the inner zones of a granule, whereas they were present in the digestate only after process recovery. This finding indicated more favorable microhabitats inside the granules that supported process recovery. Thus, the granule formation triggered by calcium oxide addition served as a tool to influence the composition of the microbial community and to stabilize the process after overloading with oil. PMID- 27681910 TI - Extensive Intestinal Resection Triggers Behavioral Adaptation, Intestinal Remodeling and Microbiota Transition in Short Bowel Syndrome. AB - Extensive resection of small bowel often leads to short bowel syndrome (SBS). SBS patients develop clinical mal-absorption and dehydration relative to the reduction of absorptive area, acceleration of gastrointestinal transit time and modifications of the gastrointestinal intra-luminal environment. As a consequence of severe mal-absorption, patients require parenteral nutrition (PN). In adults, the overall adaptation following intestinal resection includes spontaneous and complex compensatory processes such as hyperphagia, mucosal remodeling of the remaining part of the intestine and major modifications of the microbiota. SBS patients, with colon in continuity, harbor a specific fecal microbiota that we called "lactobiota" because it is enriched in the Lactobacillus/Leuconostoc group and depleted in anaerobic micro-organisms (especially Clostridium and Bacteroides). In some patients, the lactobiota-driven fermentative activities lead to an accumulation of fecal d/l-lactates and an increased risk of d encephalopathy. Better knowledge of clinical parameters and lactobiota characteristics has made it possible to stratify patients and define group at risk for d-encephalopathy crises. PMID- 27681908 TI - Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants. AB - Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics. PMID- 27681912 TI - Fed-Batch Production of Bacterial Ghosts Using Dielectric Spectroscopy for Dynamic Process Control. AB - The Bacterial Ghost (BG) platform technology evolved from a microbiological expression system incorporating the phiX174 lysis gene E. E-lysis generates empty but structurally intact cell envelopes (BGs) from Gram-negative bacteria which have been suggested as candidate vaccines, immunotherapeutic agents or drug delivery vehicles. E-lysis is a highly dynamic and complex biological process that puts exceptional demands towards process understanding and control. The development of a both economic and robust fed-batch production process for BGs required a toolset capable of dealing with rapidly changing concentrations of viable biomass during the E-lysis phase. This challenge was addressed using a transfer function combining dielectric spectroscopy and soft-sensor based biomass estimation for monitoring the rapid decline of viable biomass during the E-lysis phase. The transfer function was implemented to a feed-controller, which followed the permittivity signal closely and was capable of maintaining a constant specific substrate uptake rate during lysis phase. With the described toolset, we were able to increase the yield of BG production processes by a factor of 8-10 when compared to currently used batch procedures reaching lysis efficiencies >98%. This provides elevated potentials for commercial application of the Bacterial Ghost platform technology. PMID- 27681915 TI - Establishment of a Quality Management System Based on ISO 9001 Standard in a Public Service Fungal Culture Collection. AB - Collaborations between different Microbiological Resource Centres (mBRCs) and ethical sourcing practices are mandatory to guarantee biodiversity conservation, successful and sustainable preservation and fair share of benefits that arise from the use of genetic resources. Since microbial Culture Collections (CCs) are now engaged in meeting high quality operational standards, they are facing the challenge of establishing quality control criteria to certify their biological materials. The authentication/certification of strains is nowadays a demand from the bioeconomy sector for the global operation of mBRCs. The achievement of consistent quality assurance and trust within the mBRCs and microbial CCs context is a dynamic and never-ending process. A good option to facilitate that process is to implement a Quality Management System (QMS) based on the ISO 9001 standard. Here, we report a detailed description of all the steps taken for the QMS implementation at the Portuguese CC of filamentous fungi: Micoteca da Universidade do Minho (MUM). Our aim is to provide guidelines for the certification of other CCs, so that they can also enhance the search and choice of the most consistent, reliable, and effective operating methods, with assured procedures and validation of preservation; and guarantee trustworthy relations with all stakeholders. PMID- 27681913 TI - New Dimensions in Microbial Ecology-Functional Genes in Studies to Unravel the Biodiversity and Role of Functional Microbial Groups in the Environment. AB - During the past decades, tremendous advances have been made in the possibilities to study the diversity of microbial communities in the environment. The development of methods to study these communities on the basis of 16S rRNA gene sequences analysis was a first step into the molecular analysis of environmental communities and the study of biodiversity in natural habitats. A new dimension in this field was reached with the introduction of functional genes of ecological importance and the establishment of genetic tools to study the diversity of functional microbial groups and their responses to environmental factors. Functional gene approaches are excellent tools to study the diversity of a particular function and to demonstrate changes in the composition of prokaryote communities contributing to this function. The phylogeny of many functional genes largely correlates with that of the 16S rRNA gene, and microbial species may be identified on the basis of functional gene sequences. Functional genes are perfectly suited to link culture-based microbiological work with environmental molecular genetic studies. In this review, the development of functional gene studies in environmental microbiology is highlighted with examples of genes relevant for important ecophysiological functions. Examples are presented for bacterial photosynthesis and two types of anoxygenic phototrophic bacteria, with genes of the Fenna-Matthews-Olson-protein (fmoA) as target for the green sulfur bacteria and of two reaction center proteins (pufLM) for the phototrophic purple bacteria, with genes of adenosine-5'phosphosulfate (APS) reductase (aprA), sulfate thioesterase (soxB) and dissimilatory sulfite reductase (dsrAB) for sulfur oxidizing and sulfate reducing bacteria, with genes of ammonia monooxygenase (amoA) for nitrifying/ammonia-oxidizing bacteria, with genes of particulate nitrate reductase and nitrite reductases (narH/G, nirS, nirK) for denitrifying bacteria and with genes of methane monooxygenase (pmoA) for methane oxidizing bacteria. PMID- 27681914 TI - Microbiome, Metabolome and Inflammatory Bowel Disease. AB - Inflammatory Bowel Disease (IBD) is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn's Disease (CD) or Ulcerative Colitis (UC), two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis. PMID- 27681916 TI - A Look inside the Listeria monocytogenes Biofilms Extracellular Matrix. AB - Listeria monocytogenes is a foodborne pathogen able to persist in food industry and is responsible for a severe illness called listeriosis. The ability of L. monocytogenes to persist in environments is due to its capacity to form biofilms that are a sessile community of microorganisms embedded in a self-produced matrix of extracellular polymeric substances (EPS's). In this review, we summarized recent efforts performed in order to better characterize the polymeric substances that compose the extracellular matrix (ECM) of L. monocytogenes biofilms. EPS extraction and analysis led to the identification of polysaccharides, proteins, extracellular DNA, and other molecules within the listerial ECM. All this knowledge will be useful for increasing food protection, suggesting effective strategies for the minimization of persistence of L. monocytogenes in food industry environments. PMID- 27681917 TI - Highly Variable Bacterial Communities Associated with the Octocoral Antillogorgia elisabethae. AB - Antillogorgia elisabethae (synonymous with Pseudopterogorgia elisabethae) is a common branching octocoral in Caribbean reef ecosystems. A. elisabethae is a rich source of anti-inflammatory diterpenes, thus this octocoral has been the subject of numerous natural product investigations, yet relatively little is known regarding the composition, diversity and the geographic and temporal stability of its microbiome. To characterize the composition, diversity and stability of bacterial communities of Bahamian A. elisabethae populations, 17 A. elisabethae samples originating from five sites within The Bahamas were characterized by 16S rDNA pyrosequencing. A. elisabethae bacterial communities were less diverse and distinct from those of surrounding seawater samples. Analyses of alpha- and beta diversity revealed that A. elisabethae bacterial communities were highly variable between A. elisabethae samples from The Bahamas. This contrasts results obtained from a previous study of three specimens collected from Providencia Island, Colombia, which found A. elisabethae bacterial communities to be highly structured. Taxa belonging to the Rhodobacteriales, Rhizobiales, Flavobacteriales and Oceanospiralles were identified as potential members of the A. elisabethae core microbiome. PMID- 27681918 TI - Enrichment of Fusobacteria in Sea Surface Oil Slicks from the Deepwater Horizon Oil Spill. AB - The Deepwater Horizon (DWH) oil spill led to rapid microbial community shifts in the Gulf of Mexico, including the formation of unprecedented quantities of marine oil snow (MOS) and of a massive subsurface oil plume. The major taxa that bloomed in sea surface oil slicks during the spill included Cycloclasticus, and to a lesser extent Halomonas, Alteromonas, and Pseudoalteromonas-organisms that grow and degrade oil hydrocarbons aerobically. Here, we show that sea surface oil slicks at DWH contained obligate and facultative anaerobic taxa, including members of the obligate anaerobic phylum Fusobacteria that are commonly found in marine sediment environments. Pyrosequencing analysis revealed that Fusobacteria were strongly selected for when sea surface oil slicks were allowed to develop anaerobically. These organisms have been found in oil-contaminated sediments in the Gulf of Mexico, in deep marine oil reservoirs, and other oil-contaminated sites, suggesting they have putative hydrocarbon-degrading qualities. The occurrence and strong selection for Fusobacteria in a lab-based incubation of a sea surface oil slick sample collected during the spill suggests that these organisms may have become enriched in anaerobic zones of suspended particulates, such as MOS. Whilst the formation and rapid sinking of MOS is recognised as an important mechanism by which a proportion of the Macondo oil had been transported to the sea floor, its role in potentially transporting microorganisms, including oil-degraders, from the upper reaches of the water column to the seafloor should be considered. The presence of Fusobacteria on the sea surface-a highly oxygenated environment-is intriguing, and may be explained by the vertical upsurge of oil that provided a carrier to transport these organisms from anaerobic/micro-aerophilic zones in the oil plume or seabed to the upper reaches of the water column. We also propose that the formation of rapidly-sinking MOS may have re-transported these, and other microbial taxa, to the sediment in the Gulf of Mexico. PMID- 27681919 TI - Diagnostic Procedures to Detect Chlamydia trachomatis Infections. AB - The intracellular life style of chlamydia and the ability to cause persistent infections with low-grade replication requires tests with high analytical sensitivity to directly detect C. trachomatis (CT) in medical samples. Nucleic acid amplification tests (NAATs) are the most sensitive assays with a specificity similar to cell culture and are considered the method of choice for CT detection. In addition, NAATs can be performed on various clinical specimens that do not depend on specific transport and storage conditions, since NAATs do not require infectious bacteria. In the case of lower genital tract infections, first void urine and vaginal swabs are the recommended specimens for testing males and females, respectively. Infections of anorectal, oropharyngeal and ocular epithelia should also be tested by NAAT analysis of corresponding mucosal swabs. In particular, anorectal infections of men who have sex with men (MSM) should include evaluation of lymphogranuloma venereum (LGV) by identification of genotypes L1, L2 or L3. Detection of CT antigens by enzyme immunoassay (EIAs) or rapid diagnostic tests (RDTs) are unsuitable due to insufficient sensitivity and specificity. Recent PCR-based RDTs, however, are non-inferior to standard NAATs, and might be used at the point-of-care. Serology finds application in the diagnostic work-up of suspected chronic CT infection but is inappropriate to diagnose acute infections. PMID- 27681920 TI - Biofilms from Klebsiella pneumoniae: Matrix Polysaccharide Structure and Interactions with Antimicrobial Peptides. AB - Biofilm matrices of two Klebsiella pneumoniae clinical isolates, KpTs101 and KpTs113, were investigated for their polysaccharide composition and protective effects against antimicrobial peptides. Both strains were good biofilm producers, with KpTs113 forming flocs with very low adhesive properties to supports. Matrix exopolysaccharides were isolated and their monosaccharide composition and glycosidic linkage types were defined. KpTs101 polysaccharide is neutral and composed only of galactose, in both pyranose and furanose ring configurations. Conversely, KpTs113 polysaccharide is anionic due to glucuronic acid units, and also contains glucose and mannose residues. The susceptibility of the two strains to two bovine cathelicidin antimicrobial peptides, BMAP-27 and Bac7(1-35), was assessed using both planktonic cultures and biofilms. Biofilm matrices exerted a relevant protection against both antimicrobials, which act with quite different mechanisms. Similar protection was also detected when antimicrobial peptides were tested against planktonic bacteria in the presence of the polysaccharides extracted from KpTs101 and KpTs113 biofilms, suggesting sequestering adduct formation with antimicrobials. Circular dichroism experiments on BMAP-27 in the presence of increasing amounts of either polysaccharide confirmed their ability to interact with the peptide and induce an alpha-helical conformation. PMID- 27681921 TI - Immunoregulatory Effects Triggered by Lactic Acid Bacteria Exopolysaccharides: New Insights into Molecular Interactions with Host Cells. AB - Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions. In addition, we describe our studies using porcine intestinal epithelial cells (PIE cells) as a model to evaluate the molecular interactions of EPS from two immunobiotic LAB strains and the host cells. Our studies showed that EPS from immunobiotic LAB have anti-inflammatory capacities in PIE cells since they are able to reduce the production of inflammatory cytokines in cells challenged with the Toll-like receptor (TLR)-4-agonist lipopolysaccharide. The effects of EPS were dependent on TLR2, TLR4, and negative regulators of TLR signaling. We also reported that the radioprotective 105 (RP105)/MD1 complex, a member of the TLR family, is partially involved in the immunoregulatory effects of the EPS from LAB. Our work described, for the first time, that LAB and their EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependent manner. A continuing challenge for the future is to reveal more effector-receptor relationships in immunobiotic-host interactions that contribute to the beneficial effects of these bacteria on mucosal immune homeostasis. A detailed molecular understanding should lead to a more rational use of immunobiotics in general, and their EPS in particular, as efficient prevention and therapies for specific immune-related disorders in humans and animals. PMID- 27681922 TI - Chlamydia-Like Organisms (CLOs) in Finnish Ixodes ricinus Ticks and Human Skin. AB - Ticks carry several human pathogenic microbes including Borreliae and Flavivirus causing tick-born encephalitis. Ticks can also carry DNA of Chlamydia-like organisms (CLOs). The purpose of this study was to investigate the occurrence of CLOs in ticks and skin biopsies taken from individuals with suspected tick bite. DNA from CLOs was detected by pan-Chlamydiales-PCR in 40% of adult ticks from southwestern Finland. The estimated minimal infection rate for nymphs and larvae (studied in pools) was 6% and 2%, respectively. For the first time, we show CLO DNA also in human skin as 68% of all skin biopsies studied contained CLO DNA as determined through pan-Chlamydiales-PCR. Sequence analyses based on the 16S rRNA gene fragment indicated that the sequences detected in ticks were heterogeneous, representing various CLO families; whereas the majority of the sequences from human skin remained "unclassified Chlamydiales" and might represent a new family level lineage. CLO sequences detected in four skin biopsies were most closely related to "uncultured Chlamydial bacterium clones from Ixodes ricinus ticks" and two of them were very similar to CLO sequences from Finnish ticks. These results suggest that CLO DNA is present in human skin; ticks carry CLOs and could potentially transmit CLOs to humans. PMID- 27681924 TI - Coinfection of Chlamydiae and other Bacteria in Reactive Arthritis and Spondyloarthritis: Need for Future Research. AB - Reactive (inflammatory) arthritis has been known for many years to follow genital infection with the intracellular bacterial pathogen Chlamydia trachomatis in some individuals. Recent studies from several groups have demonstrated that a related bacterium, the respiratory pathogen Chlamydia pneumoniae, can elicit a similar arthritis. Studies of these organisms, and of a set of gastrointestinal pathogens also associated with engendering inflammatory arthritis, have been relatively extensive. However, reports focusing on coinfections with these and/or other organisms, and the effects of such coinfections on the host immune and other systems, have been rare. In this article, we review the extant data regarding infections by multiple pathogens in the joint as they relate to engendering arthritis, and we suggest a number of research areas that must be given a high priority if we are to understand, and therefore to treat in an effective manner, such arthritides. PMID- 27681925 TI - Correia Repeat Enclosed Elements and Non-Coding RNAs in the Neisseria Species. AB - Neisseria gonorrhoeae is capable of causing gonorrhoea and more complex diseases in the human host. Neisseria meningitidis is a closely related pathogen that shares many of the same genomic features and virulence factors, but causes the life threatening diseases meningococcal meningitis and septicaemia. The importance of non-coding RNAs in gene regulation has become increasingly evident having been demonstrated to be involved in regulons responsible for iron acquisition, antigenic variation, and virulence. Neisseria spp. contain an IS like element, the Correia Repeat Enclosed Element, which has been predicted to be mobile within the genomes or to have been in the past. This repeat, present in over 100 copies in the genome, has the ability to alter gene expression and regulation in several ways. We reveal here that Correia Repeat Enclosed Elements tend to be near non-coding RNAs in the Neisseria spp., especially N. gonorrhoeae. These results suggest that Correia Repeat Enclosed Elements may have disrupted ancestral regulatory networks not just through their influence on regulatory proteins but also for non-coding RNAs. PMID- 27681926 TI - Phylogenetic Characterization of Marine Benthic Archaea in Organic-Poor Sediments of the Eastern Equatorial Pacific Ocean (ODP Site 1225). AB - Sequencing surveys of microbial communities in marine subsurface sediments have focused on organic-rich, continental margins; the database for organic-lean deep sea sediments from mid-ocean regions is underdeveloped. The archaeal community in subsurface sediments of ODP Site 1225 in the eastern equatorial Pacific (3760 m water depth; 1.1 and 7.8 m sediment depth) was analyzed by PCR, cloning and sequencing, and by denaturant gradient gel electrophoresis (DGGE) of 16S rRNA genes. Three uncultured archaeal lineages with different depth distributions were found: Marine Group I (MG-I) within the Thaumarchaeota, its sister lineage Marine Benthic Group A (MBG-A), the phylum-level archaeal lineage Marine Benthic Group B (also known as Deep-Sea Archaeal Group or Lokiarchaeota), and the Deep-Sea Euryarchaeotal Group 3. The MG-I phylotypes included representatives of sediment clusters that are distinct from the pelagic members of this phylum. On the scale from fully oxidized, extremely organic carbon-depleted sediments (for example, those the South Pacific Gyre) to fully reduced, organic carbon-rich marine subsurface sediments (such as those of the Peru Margin), Ocean Drilling Program (ODP) Site 1225 falls into the non-extreme organic carbon-lean category, and harbors archaeal communities from both ends of the spectrum. PMID- 27681927 TI - Achromobacter Species Isolated from Cystic Fibrosis Patients Reveal Distinctly Different Biofilm Morphotypes. AB - Achromobacter species have attracted attention as emerging pathogens in cystic fibrosis. The clinical significance of Achromobacter infection is not yet fully elucidated; however, their intrinsic resistance to antimicrobials and ability to form biofilms renders them capable of establishing long-term chronic infections. Still, many aspects of Achromobacter biofilm formation remain uncharacterized. In this study, we characterized biofilm formation in clinical isolates of Achromobacter and investigated the effect of challenging the biofilm with antimicrobials and/or enzymes targeting the extracellular matrix. In vitro biofilm growth and subsequent visualization by confocal microscopy revealed distinctly different biofilm morphotypes: a surface-attached biofilm morphotype of small aggregates and an unattached biofilm morphotype of large suspended aggregates. Aggregates consistent with our in vitro findings were visualized in sputum samples from cystic fibrosis patients using an Achromobacter specific peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) probe, confirming the presence of Achromobacter biofilms in the CF lung. High antibiotic tolerance was associated with the biofilm phenotype, and biocidal antibiotic concentrations were up to 1000 fold higher than for planktonic cultures. Treatment with DNase or subtilisin partially dispersed the biofilm and reduced the tolerance to specific antimicrobials, paving the way for further research into using dispersal mechanisms to improve treatment strategies. PMID- 27681923 TI - Insights on the Horizontal Gene Transfer of Carbapenemase Determinants in the Opportunistic Pathogen Acinetobacter baumannii. AB - Horizontal gene transfer (HGT) is a driving force to the evolution of bacteria. The fast emergence of antimicrobial resistance reflects the ability of genetic adaptation of pathogens. Acinetobacter baumannii has emerged in the last few decades as an important opportunistic nosocomial pathogen, in part due to its high capacity of acquiring resistance to diverse antibiotic families, including to the so-called last line drugs such as carbapenems. The rampant selective pressure and genetic exchange of resistance genes hinder the effective treatment of resistant infections. A. baumannii uses all the resistance mechanisms to survive against carbapenems but production of carbapenemases are the major mechanism, which may act in synergy with others. A. baumannii appears to use all the mechanisms of gene dissemination. Beyond conjugation, the mostly reported recent studies point to natural transformation, transduction and outer membrane vesicles-mediated transfer as mechanisms that may play a role in carbapenemase determinants spread. Understanding the genetic mobilization of carbapenemase genes is paramount in preventing their dissemination. Here we review the carbapenemases found in A. baumannii and present an overview of the current knowledge of contributions of the various HGT mechanisms to the molecular epidemiology of carbapenem resistance in this relevant opportunistic pathogen. PMID- 27681928 TI - Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus. AB - Biofilms formed by Staphylococcus aureus is a serious complication to the use of medical implants. A central part of the pathogenesis relies on S. aureus' ability to adhere to host extracellular matrix proteins, which adsorb to medical implants and stimulate biofilm formation. Being coagulase positive, S. aureus furthermore induces formation of fibrin fibers from fibrinogen in the blood. Consequently, we hypothesized that fibrin is a key component of the extracellular matrix of S. aureus biofilms under in vivo conditions, and that the recalcitrance of biofilm infections can be overcome by combining antibiotic treatment with a fibrinolytic drug. We quantified S. aureus USA300 biofilms grown on peg-lids in brain heart infusion (BHI) broth with 0%-50% human plasma. Young (2 h) and mature (24 h) biofilms were then treated with streptokinase to determine if this lead to dispersal. Then, the minimal biofilm eradication concentration (MBEC) of 24 h old biofilms was measured for vancomycin and daptomycin alone or in combination with 10 ug/mL rifampicin in the presence or absence of streptokinase in the antibiotic treatment step. Finally, biofilms were visualized by confocal laser scanning microscopy. Addition of human plasma stimulated biofilm formation in BHI in a dose-dependent manner, and biofilms could be partially dispersed by streptokinase. The biofilms could be eradicated with physiologically relevant concentrations of streptokinase in combination with rifampicin and vancomycin or daptomycin, which are commonly used antibiotics for treatment of S. aureus infections. Fibronolytic drugs have been used to treat thromboembolic events for decades, and our findings suggest that their use against biofilm infections has the potential to improve the efficacy of antibiotics in treatment of S. aureus biofilm infections. PMID- 27681929 TI - Biofilm Forming Lactobacillus: New Challenges for the Development of Probiotics. AB - Probiotics are live bacteria, generally administered in food, conferring beneficial effects to the host because they help to prevent or treat diseases, the majority of which are gastrointestinal. Numerous investigations have verified the beneficial effect of probiotic strains in biofilm form, including increased resistance to temperature, gastric pH and mechanical forces to that of their planktonic counterparts. In addition, the development of new encapsulation technologies, which have exploited the properties of biofilms in the creation of double coated capsules, has given origin to fourth generation probiotics. Up to now, reviews have focused on the detrimental effects of biofilms associated with pathogenic bacteria. Therefore, this work aims to amalgamate information describing the biofilms of Lactobacillus strains which are used as probiotics, particularly L. rhamnosus, L. plantarum, L. reuteri, and L. fermentum. Additionally, we have reviewed the development of probiotics using technology inspired by biofilms. PMID- 27681930 TI - Adhesion Properties of Lactic Acid Bacteria on Intestinal Mucin. AB - Lactic acid bacteria (LAB) are Gram-positive bacteria that are natural inhabitants of the gastrointestinal (GI) tracts of mammals, including humans. Since Mechnikov first proposed that yogurt could prevent intestinal putrefaction and aging, the beneficial effects of LAB have been widely demonstrated. The region between the duodenum and the terminal of the ileum is the primary region colonized by LAB, particularly the Lactobacillus species, and this region is covered by a mucus layer composed mainly of mucin-type glycoproteins. The mucus layer plays a role in protecting the intestinal epithelial cells against damage, but is also considered to be critical for the adhesion of Lactobacillus in the GI tract. Consequently, the adhesion exhibited by lactobacilli on mucin has attracted attention as one of the critical factors contributing to the persistent beneficial effects of Lactobacillus in a constantly changing intestinal environment. Thus, understanding the interactions between Lactobacillus and mucin is crucial for elucidating the survival strategies of LAB in the GI tract. This review highlights the properties of the interactions between Lactobacillus and mucin, while concomitantly considering the structure of the GI tract from a histochemical perspective. PMID- 27681931 TI - Biotin Auxotrophy and Biotin Enhanced Germ Tube Formation in Candida albicans. AB - Due to the increased number of immunocompromised patients, infections with the pathogen Candida albicans have significantly increased in recent years. C. albicans transition from yeast to germ tubes is one of the essential factors for virulence. In this study we noted that Lee's medium, commonly used to induce filamentation, contained 500-fold more biotin than needed for growth and 40-fold more biotin than is typically added to growth media. Thus, we investigated the effects of excess biotin on growth rate and filamentation by C. albicans in different media. At 37 degrees C, excess biotin (4 uM) enhanced germ tube formation (GTF) ca. 10-fold in both Lee's medium and a defined glucose-proline medium, and ca. 4-fold in 1% serum. Two biotin precursors, desthiobiotin and 7 keto-8-aminopelargonic acid (KAPA), also stimulated GTF. During these studies we also noted an inverse correlation between the number of times the inoculum had been washed and the concentration of serum needed to stimulate GTF. C. albicans cells that had been washed eight times achieved 80% GTF with only 0.1% sheep serum. The mechanism by which 1-4 uM biotin enhances GTF is still unknown except to note that equivalent levels of biotin are needed to create an internal supply of stored biotin and biotinylated histones. Biotin did not restore filamentation for any of the four known filamentation defective mutants tested. C. albicans is auxotrophic for biotin and this biotin auxotrophy was fulfilled by biotin, desthiobiotin, or KAPA. However, biotin auxotrophy is not temperature dependent or influenced by the presence of 5% CO2. Biotin starvation upregulated the biotin biosynthetic genes BIO2, BIO3, and BIO4 by 11-, 1500-, and 150-fold, respectively, and BIO2p is predicted to be mitochondrion-localized. Based on our findings, we suggest that biotin has two roles in the physiology of C. albicans, one as an enzymatic cofactor and another as a morphological regulator. Finally, we found no evidence supporting prior claims that C. albicans only forms hyphae at very low biotin (0.1 nM) growth conditions. PMID- 27681933 TI - The impact of item-writing flaws and item complexity on examination item difficulty and discrimination value. AB - BACKGROUND: Failure to adhere to standard item-writing guidelines may render examination questions easier or more difficult than intended. Item complexity describes the cognitive skill level required to obtain a correct answer. Higher cognitive examination items promote critical thinking and are recommended to prepare students for clinical training. This study evaluated faculty-authored examinations to determine the impact of item-writing flaws and item complexity on the difficulty and discrimination value of examination items used to assess third year veterinary students. METHODS: The impact of item-writing flaws and item complexity (cognitive level I-V) on examination item difficulty and discrimination value was evaluated on 1925 examination items prepared by clinical faculty for third year veterinary students. RESULTS: The mean (+/- SE) percent correct (83.3 % +/- 17.5) was consistent with target values in professional education, and the mean discrimination index (0.18 +/- 0.17) was slightly lower than recommended (0.20). More than one item-writing flaw was identified in 37.3 % of questions. The most common item-writing flaws were awkward stem structure, implausible distractors, longest response is correct, and responses are series of true-false statements. Higher cognitive skills (complexity level III-IV) were required to correctly answer 38.4 % of examination items. As item complexity increased, item difficulty and discrimination values increased. The probability of writing discriminating, difficult examination items decreased when implausible distractors and all of the above were used, and increased if the distractors were comprised of a series of true/false statements. Items with four distractors were not more difficult or discriminating than items with three distractors. CONCLUSION: Preparation of examination questions targeting higher cognitive levels will increase the likelihood of constructing discriminating items. Use of implausible distractors to complete a five-option multiple choice question does not strengthen the discrimination value. PMID- 27681932 TI - DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. AB - BACKGROUND: Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC 159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. METHODOLOGY/PRINCIPAL FINDINGS: To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9 fold higher than moxifloxacin. Also the fluoroquinolone-mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. CONCLUSIONS/SIGNIFICANCE: The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC 159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans. PMID- 27681934 TI - Plasma Catestatin in Patients with Acute Coronary Syndrome. AB - OBJECTIVES: To measure plasma catestatin levels in patients with acute coronary syndrome and investigate whether there is an association between catestatin levels and long-term outcome. METHODS: Patients (n = 170) with suspected acute coronary syndrome who underwent emergency coronary angiography were enrolled, including 46 with acute ST-segment elevation myocardial infarction (STEMI), 89 with unstable angina pectoris (UAP), and 35 without coronary artery disease (CAD). All patients were followed for 2 years to measure the occurrence of major adverse cardiovascular events (MACEs), including death from a cardiovascular cause, recurrent acute myocardial infarction, or hospital admission for heart failure or revascularization. RESULTS: On average, the plasma catestatin levels in patients with STEMI (0.80 +/- 0.62 ng/ml) and UAP (0.99 +/- 0.63 ng/ml) were significantly lower than the levels seen in the control group with no evidence of CAD (1.38 +/- 0.98 ng/ml; p = 0.001). In multivariable linear regression, body mass index, presence of hypertension, and type of CAD were independently related to the plasma catestatin level. However, there were no significant differences in MACEs between patients with high and low levels of catestatin. CONCLUSIONS: The plasma catestatin levels in patients with STEMI and UAP were lower than the levels seen in patients without CAD. PMID- 27681935 TI - Postmenopausal osteoporosis. AB - Osteoporosis is a metabolic bone disorder that is characterized by low bone mass and micro-architectural deterioration of bone tissue. Fractures of the proximal femur, the vertebrae and the distal radius are the most frequent osteoporotic fractures, although most fractures in the elderly are probably at least partly related to bone fragility. The incidence of fractures varies greatly by country, but on average up to 50% of women >50 years of age are at risk of fractures. Fractures severely affect the quality of life of an individual and are becoming a major public health problem owing to the ageing population. Postmenopausal osteoporosis, resulting from oestrogen deficiency, is the most common type of osteoporosis. Oestrogen deficiency results in an increase in bone turnover owing to effects on all types of bone cells. The imbalance in bone formation and resorption has effects on trabecular bone (loss of connectivity) and cortical bone (cortical thinning and porosity). Osteoporosis is diagnosed using bone density measurements of the lumbar spine and proximal femur. Preventive strategies to improve bone health include diet, exercise and abstaining from smoking. Fractures may be prevented by reducing falls in high-risk populations. Several drugs are licensed to reduce fracture risk by slowing down bone resorption (such as bisphosphonates and denosumab) or by stimulating bone formation (such as teriparatide). Improved understanding of the cellular basis for osteoporosis has resulted in new drugs targeted to key pathways, which are under development. PMID- 27681936 TI - Bone Response of Loaded Periodontal Ligament. AB - The tooth-periodontal ligament-alveolar bone complex acts symbiotically to dissipate the mechanical loads incurred during mastication and/or orthodontic tooth movement. The periodontal ligament functions both in the tension and compression. At the molecular and celleular levels, the loads in the periodontal ligament trigger mechanobiological events in the alveolar bone, which leads to bone modeling and remodeling. The current review focuses on the bone response to mechanical loading of the periodontal ligament on the tension and pressure sides. Understanding the bone response has major implications for dentistry, including a better understanding of the different types of orthodontic tooth movement. PMID- 27681937 TI - Landscape-scale spatial heterogeneity in phytodetrital cover and megafauna biomass in the abyss links to modest topographic variation. AB - Sinking particulate organic matter (POM, phytodetritus) is the principal limiting resource for deep-sea life. However, little is known about spatial variation in POM supply to the abyssal seafloor, which is frequently assumed to be homogenous. In reality, the abyss has a highly complex landscape with millions of hills and mountains. Here, we show a significant increase in seabed POM % cover (by ~1.05 times), and a large significant increase in megafauna biomass (by ~2.5 times), on abyssal hill terrain in comparison to the surrounding plain. These differences are substantially greater than predicted by current models linking water depth to POM supply or benthic biomass. Our observed variations in POM % cover (phytodetritus), megafauna biomass, sediment total organic carbon and total nitrogen, sedimentology, and benthic boundary layer turbidity, all appear to be consistent with topographically enhanced current speeds driving these enhancements. The effects are detectable with bathymetric elevations of only 10 s of metres above the surrounding plain. These results imply considerable unquantified heterogeneity in global ecology. PMID- 27681940 TI - Candida infections in paediatrics: Results from a prospective single-centre study in a tertiary care children's hospital. AB - To describe the epidemiology of invasive Candida infection in a tertiary care paediatric hospital. Prospective single-centre survey on all Candida strains isolated from normally sterile fluids and urines in the period 2005-2015 . A total of 299 ICI were documented in 262 patients. Urinary tract infection represented the most frequent diagnosis (62%), followed by fungaemia (34%) and peritonitis (4%). Fungaemia was most frequent in children with cancer (59%) or in low birth weight neonates (61%), while urinary tract infections were more frequent in patients with urinary tract malformation. C.albicans was the most frequently isolated species (60%) compared with C. non-albicans, but differences were present according to the site of isolation and underlying conditions. Overall 90-day mortality was 7%, 13% in fungaemias, 8% in peritonitis and 2% in urinary tract infections. The rates of invasive Candida infection increased during the study period. Invasive Candida infection is diagnosed with increasing frequency in children. Site of isolation and aetiology are frequently related with the presence of underlying, favouring conditions. Mortality was not negligible, especially in the presence of more invasive infections and specific underlying conditions. PMID- 27681941 TI - When evidence of heat-related vulnerability depends on the contrast measure. AB - Many studies assessing which population subgroups are more vulnerable to heat related mortality and morbidity have been conducted in recent years. However, given the non-linear (U or J shaped) relationship of temperature with mortality and morbidity, they generally consider only a single contrast measure to report evidence of heat-related vulnerability, despite the possibility that vulnerability depends on the selected contrast measure. In this manuscript, we highlight the importance of considering such issue in further studies by providing evidence for and against heat-related vulnerability using two different temperature contrast measures. We conducted time series analyses to characterize the association between mortality and mean daily temperature in Montreal, Canada (1990-2010). We used age (>=65 vs. 0-64 years) as the effect modifier in stratified analyses. We assessed the presence of effect modification using Cochran Q tests. As contrast measures, we used (1) the percentage change in the outcome above 25 degrees C, obtained through spline functions showing a linear relationship after this threshold and (2) a comparison of two percentiles (26 vs. 20 degrees C) of the temperature. We found that evidence of effect modification depended on the contrast measure used. We encourage researchers aiming to identify populations more vulnerable to heat to perform sensitivity analyses using different contrast measures. PMID- 27681942 TI - How useful is thrombocytosis in predicting an underlying cancer in primary care? a systematic review. AB - BACKGROUND: Although the association between raised platelet count (thrombocytosis) and cancer has been reported in primary and secondary care studies, UK GPs are unaware of it, and it is insufficiently evidenced for laboratories to identify and warn of it. This systematic review aimed to identify and collate evidence from studies that have investigated thrombocytosis as an early marker of cancer in primary care. METHODS: EMBASE (OvidSP), Medline (Ovid), Web of Science and The Cochrane Library were searched for relevant studies. Eligible studies had reported estimates of the association between thrombocytosis and cancer, in adults aged >=40 in a primary care setting. Raw data from included studies were used to calculate positive predictive values and likelihood ratios (LRs) for cancer. RESULTS: Nine case-control studies were identified. Study quality was judged to be high. Included studies reported on the following cancer sites: colorectal, lung, ovary, bladder, kidney, pancreas, oesophago-gastric, uterus and breast. LRs indicated that thrombocytosis was a predictor of cancer in all sites except breast. In a consulting population, thrombocytosis is most highly predictive of lung and colorectal cancer. CONCLUSIONS: These results suggest that patients with thrombocytosis in primary care have an increased risk of cancer, and that some, but not all, cancers have raised platelets as an early marker. This finding is expected to be of use in primary care, for GPs receiving blood test results unexpectedly showing high platelet counts. Further research is needed to identify the cancers that are most strongly associated with thrombocytosis. PMID- 27681943 TI - Hexagonal Boron Nitride Tunnel Barriers Grown on Graphite by High Temperature Molecular Beam Epitaxy. AB - We demonstrate direct epitaxial growth of high-quality hexagonal boron nitride (hBN) layers on graphite using high-temperature plasma-assisted molecular beam epitaxy. Atomic force microscopy reveals mono- and few-layer island growth, while conducting atomic force microscopy shows that the grown hBN has a resistance which increases exponentially with the number of layers, and has electrical properties comparable to exfoliated hBN. X-ray photoelectron spectroscopy, Raman microscopy and spectroscopic ellipsometry measurements on hBN confirm the formation of sp2-bonded hBN and a band gap of 5.9 +/- 0.1 eV with no chemical intermixing with graphite. We also observe hexagonal moire patterns with a period of 15 nm, consistent with the alignment of the hBN lattice and the graphite substrate. PMID- 27681944 TI - Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial. AB - Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade >=3 treatment-related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF 1R, IGF-1, IGF-2 and EREG by quantitative real-time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p < 0.05) among patients with KRAS wild-type compared to those with KRAS exon 2 mutant tumours. No significant changes were found according to location of the primary tumour with only a trend towards lower expression of IGF-1 in colon compared to rectal cancers (p = 0.06). Albeit limited by the small sample size, this study does not appear to support a potential role for anti-IGF-1R agents in KRAS exon 2 mutant CRC. Data on IGF-1R, IGF-1 and IGF-2 expression here reported may be useful for patient stratification in future trials with inhibitors of the IGF pathway. PMID- 27681947 TI - Clinical recovery in linezolid-induced optic nerve toxicity. PMID- 27681946 TI - Survey: interpolation methods for whole slide image processing. AB - Evaluating whole slide images of histological and cytological samples is used in pathology for diagnostics, grading and prognosis . It is often necessary to rescale whole slide images of a very large size. Image resizing is one of the most common applications of interpolation. We collect the advantages and drawbacks of nine interpolation methods, and as a result of our analysis, we try to select one interpolation method as the preferred solution. To compare the performance of interpolation methods, test images were scaled and then rescaled to the original size using the same algorithm. The modified image was compared to the original image in various aspects. The time needed for calculations and results of quantification performance on modified images were also compared. For evaluation purposes, we used four general test images and 12 specialized biological immunohistochemically stained tissue sample images. The purpose of this survey is to determine which method of interpolation is the best to resize whole slide images, so they can be further processed using quantification methods. As a result, the interpolation method has to be selected depending on the task involving whole slide images. PMID- 27681949 TI - ? PMID- 27681945 TI - Genome-wide identification and characterization of tRNA-derived RNA fragments in land plants. AB - KEY MESSAGE: The manuscript by Alves et al. entitled "Genome-wide identification and characterization of tRNA-derived RNA fragments in land plants" describes the identification and characterization of tRNAderived sRNA fragments in plants. By combining bioinformatic analysis and genetic and molecular approaches, we show that tRF biogenesis does not rely on canonical microRNA/siRNA processing machinery (i.e., independent of DICER-LIKE proteins). Moreover, we provide evidences that the Arabidopsis S-like Ribonuclease 1 (RNS1) might be involved in the biogenesis of tRFs. Detailed analyses showed that plant tRFs are sorted into different types of ARGONAUTE proteins and that they have potential target candidate genes. Our work advances the understanding of the tRF biology in plants by providing evidences that plant and animal tRFs shared common features and raising the hypothesis that an interplay between tRFs and other sRNAs might be important to fine-tune gene expression and protein biosynthesis in plant cells. Small RNA (sRNA) fragments derived from tRNAs (3'-loop, 5'-loop, anti-codon loop), named tRFs, have been reported in several organisms, including humans and plants. Although they may interfere with gene expression, their biogenesis and biological functions in plants remain poorly understood. Here, we capitalized on small RNA sequencing data from distinct species such as Arabidopsis thaliana, Oryza sativa, and Physcomitrella patens to examine the diversity of plant tRFs and provide insight into their properties. In silico analyzes of 19 to 25-nt tRFs derived from 5' (tRF-5s) and 3'CCA (tRF-3s) tRNA loops in these three evolutionary distant species showed that they are conserved and their abundance did not correlate with the number of genomic copies of the parental tRNAs. Moreover, tRF-5 is the most abundant variant in all three species. In silico and in vivo expression analyses unraveled differential accumulation of tRFs in Arabidopsis tissues/organs, suggesting that they are not byproducts of tRNA degradation. We also verified that the biogenesis of most Arabidopsis 19-25 nt tRF-5s and tRF-3s is not primarily dependent on DICER-LIKE proteins, though they seem to be associated with ARGONAUTE proteins and have few potential targets. Finally, we provide evidence that Arabidopsis ribonuclease RNS1 might be involved in the processing and/or degradation of tRFs. Our data support the notion that an interplay between tRFs and other sRNAs might be important to fine tune gene expression and protein biosynthesis in plant cells. PMID- 27681948 TI - Theory-based self-management educational interventions on patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. AB - AIM: To synthesize the effects of theory-based self-management educational interventions on patients with type 2 diabetes (T2DM) in randomized controlled trials. BACKGROUND: Type 2 diabetes is a common chronic disease causing complications that put a heavy burden on society and reduce the quality of life of patients. Good self-management of diabetes can prevent complications and improve the quality of life of T2DM patients. DESIGN: Systematic review with meta analysis of randomized controlled trials following Cochrane methods. DATA RESOURCES: A literature search was carried out in the MEDLINE, EMBASE, CINAHL, PSYCINFO, and Web of Science databases (1980-April 2015). REVIEW METHODS: The risk of bias of these eligible studies was assessed independently by two authors using the Cochrane Collaboration's tool. The Publication bias of the main outcomes was examined. Statistical heterogeneity and random-effects model were used for meta-analysis. RESULTS: Twenty studies with 5802 participants met the inclusion criteria. The interventions in the studies were based on one or more theories which mostly belong to mid-range theories. The pooled main outcomes by random-effects model showed significant improvements in HbA1c, self-efficacy, and diabetes knowledge, but not in BMI. As for quality of life, no conclusions can be drawn as the pooled outcome became the opposite with reduced heterogeneity after one study was excluded. No significant publication bias was found in the main outcomes. CONCLUSION: To get theory-based interventions to produce more effects, the role of patients should be more involved and stronger and the education team should be trained beyond the primary preparation for the self-management education program. PMID- 27681951 TI - Cancer-associated fibroblasts are an infrequent finding in the microenvironment of proliferative verrucous leukoplakia-associated squamous cell carcinoma. AB - BACKGROUND: Cancer-associated fibroblasts (CAFs) are generally associated with negative prognostic factors. This study compares the clinicopathologic impact of CAFs in oral squamous cell carcinoma in patients with a history of proliferative verrucous leukoplakia (p-scca) and patients with conventional squamous cell carcinoma of the buccal mucosa, gingiva, and palate (c-scca). METHODS: A retrospective clinicopathologic and immunohistochemical analysis of 97 tumor specimens from 78 patients (13 patients with proliferative verrucous leukoplakia associated squamous cell carcinoma (n = 32) and conventional squamous cell carcinoma from the buccal mucosa, gingiva, and palate (n = 65) was conducted. Immunostaining with anti-alpha-smooth muscle actin (alpha-SMA) antibody was used to evaluate the presence of CAFs. RESULTS: alpha-SMA expression was an infrequent finding in p-scca and seen in only 6% of p-scca compared to 40% of c-scca (P < 0.0004). In the c-scca subgroup, alpha-SMA significantly correlated with tumor size (T) (P = 0.009), tumor thickness (P < 0.0009), perineural invasion (P = 0.009), and microscopic grade (P = 0.018). CONCLUSIONS: The presence of CAFs was an infrequent finding in our p-scca cohort which may contribute to its seemingly slower growing and less invasive growth pattern. In the cohort of c-scca patients, higher levels of CAFs correlated with microscopic invasiveness, tumor size, and perineural invasion. Practically, these are important observations as targeting strategies are being developed to combat carcinoma types where CAFs significance has been validated. PMID- 27681950 TI - [Pitfalls in the histopathological diagnostics of endometrial carcinoma and its precursors : Clinically relevant differential diagnoses, avoidance of false positive diagnoses]. AB - Making an incorrect histopathological diagnosis of an endometrial lesion may lead to unwanted loss of fertility and therapy-associated morbidity; therefore, endometrial carcinomas need to be correctly typed and differentiated from hyperplastic precursors, benign lesions and artifacts. Typical diagnostic pitfalls are described in this article. Misdiagnosing endometrial lesions can be avoided by paying thorough attention to gross as well as microscopic features and by taking crucial differential diagnoses into consideration. These are, in particular, well-differentiated endometrioid adenocarcinoma of the endometrium versus atypical endometrial hyperplasia, myoinvasive endometrioid adenocarcinoma versus atypical polypoid adenomyoma and endometrioid carcinoma versus serous carcinoma of the endometrium with a predominantly glandular pattern. It is also important to consider the possibility of a false positive diagnosis of atypical endometrial hyperplasia or carcinoma in cases of biopsy-induced artifacts. PMID- 27681952 TI - Surgical treatment of pseudotumor cerebri. AB - AIM: To share our experience with idiopathic intracranial hypertension. MATERIAL AND METHODS: All patients believed to have pseudotumor cerebri underwent a fundus oculi examination to confirm the existence of papillary stasis and lumbar puncture (LP) to measure cerebrospinal fluid (CSF) pressure. Patients who did not respond to medical treatment underwent fundus oculi examinations at 3-week intervals. Patients with CFS pressures exceeding 240 mm H2O underwent at least three LPs at 3-day intervals. Patients with higher CFS pressures were treated surgically. RESULTS: The mean patient age was 40.8 (range 31-58) years and the mean body mass index (BMI) was 30.9 (range 28.8-36.4) kg/m2. Papillary stasis was observed in 15 (46.8%) cases. The mean initial CSF pressure was 455.6 (range 360 560) mmHg, and after a mean of 4.3 (range 3-6) repeat measurements, this decreased to 213.4 (range 160-320) mmHg (Table I). Complications in our series included a lumbar pouch in three patients, and an abdominal pouch, meningitis, and abdominal migration in one patient each. DISCUSSION: Surgical treatment of idiopathic intracranial hypertension is necessary when the intracranial pressure does not decrease despite medical treatment and repeat LP. CONCLUSIONS: Idiopathic intracranial hypertension is a clinical syndrome of unclear pathogenesis that is closely related to obesity. KEY WORDS: Cerebrospinal fluid, Idiopathic intracranial hypertension, Pseudotumor cerebri, Obesity. PMID- 27681953 TI - Erratum to: Isolated cardiac sarcoidosis: A focused review of an under-recognized entity. PMID- 27681954 TI - Non-invasive imaging in suspected coronary artery disease: Choosing the right test from the first time. PMID- 27681955 TI - Stress myocardial blood flow correlates with ventricular function and synchrony better than myocardial perfusion reserve: A Nitrogen-13 ammonia PET study. AB - BACKGROUND: Cardiac PET quantifies stress myocardial blood flow (MBF) and perfusion reserve (MPR), while ECG-gated datasets can measure components of ventricular function simultaneously. Stress MBF seems to outperform MPR in the detection of significant CAD. However, it is uncertain which perfusion measurement is more related to ventricular function. We hypothesized that stress MBF correlates with ventricular function better than MPR in patients studied for suspected myocardial ischemia. METHODS: We studied 248 patients referred to a rest and adenosine-stress Nitrogen-13 ammonia PET. We performed a multivariate analysis using systolic function (left ventricular ejection fraction, LVEF), diastolic function (mean filling rate in diastole, MFR/3), and synchrony (Entropy) as the outcome variables, and stress MBF, MPR, and relevant covariates as the predictors. Secondarily, we repeated the analysis for the subgroup of patients with and without a previous myocardial infarction (MI). RESULTS: 166 male and 82 female patients (mean age 63 +/- 11 and 67 +/- 11 year, respectively) were included. 60% of the patients presented hypertension, 57% dyslipidemia, 21% type 2 diabetes mellitus, 45% smoking, and 34.7% a previous MI. Mean stress MBF was 1.99 +/- 0.75 mL/g/min, MPR = 2.55 +/- 0.89, LVEF = 61.6 +/- 15%, MFR/3 = 1.12 +/- 0.38 EDV/s, and Entropy = 45.6 +/- 11.3%. There was a significant correlation between stress MBF (P < .001) and ventricular function. This was stronger than the one for MPR (P = .063). Sex, age, diabetes, and extent of previous MI were also significant predictors. Results were similar for the analyses of the 2 subgroups. CONCLUSION: Stress MBF is better correlated with ventricular function than MPR, as evaluated by Nitrogen-13 ammonia PET, independently from other relevant cardiovascular risk factors and clinical covariates. This relationship between coronary vasodilatory capacity and ventricular function is sustained across groups with and without a previous MI. PMID- 27681956 TI - Clinical outcome and morbidity in pediatric patients with nasopharyngeal cancer treated with chemoradiotherapy. AB - OBJECTIVES: The aim of the study was to evaluate the outcome and treatment related morbidity in pediatric patients with nasopharyngeal carcinoma (NPC) treated with chemoradiotherapy. METHODS: We did a retrospective review of 41 pediatric patients diagnosed with NPC between 2000 and 2013. The majority of the patients were treated with neoadjuvant chemotherapy followed by concurrent chemoradiation with the dose of 70 Gy in 35 fractions. Eight patients were treated with intensity-modulated radiation therapy, while the remaining with three-dimensional conformal radiation therapy or two-dimensional simulation technique. RESULTS: The median age of the patients was 14 years (range 6-20 years). Most of the patients had locoregionally advanced disease (stage III/IVA/IVB). The histology of all the cases was undifferentiated carcinoma. Immunohistochemistry for the Epstein-Barr virus-Latent membrane protein 1 was positive in nine of the 13 tested cases. The median follow-up for all and the surviving patients was 26.6 months (range 2-140.8) and 51.2 months, respectively. The 3-year overall survival (OS) and event-free survival (EFS) rates were estimated at 83.7% (95% confidence interval [CI]: 64.8-93%) and 55.8% (95%CI: 38.7-69.8%), respectively. Distant metastases were the predominant pattern of failure. Treatment response showed an independent association with OS. T classification (T1/T2 vs. T3/T4) was significantly associated with EFS. Xerostomia, hypothyroidism, dental caries, neck fibrosis, trismus, and dysphagia were the common late effects in survivors. Radiation myelitis was observed in one patient. CONCLUSIONS: Treatment with neoadjuvant chemotherapy followed by concurrent chemoradiation provides good survival outcomes in pediatric NPC. The quality of life of the survivors is a pertinent area that necessitates consideration. PMID- 27681957 TI - Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load. AB - OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load. PMID- 27681959 TI - Accuracy of the serum intestinal fatty-acid-binding protein for diagnosis of acute intestinal ischemia: a meta-analysis. AB - Numerous studies have investigated the utility of serum intestinal fatty-acid binding protein (I-FABP) in differentiating acute intestinal ischemia from acute abdomen. However, the results remain controversial. The aim of this meta-analysis is to determine the overall accuracy of serum I-FABP in the diagnosis of acute intestinal ischemia. Publications addressing the accuracy of serum I-FABP in the diagnosis of ischemic bowel diseases were selected from databases. The values of true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The overall diagnostic performance was assessed using a summary receiver operating characteristic curve (SROC) and area under curve (AUC). Nine studies that collectively included 1246 patients met the eligible criteria. The pooled sensitivity, specificity, DOR, PLR, and NLR were 0.80 (95% CI: 0.72-0.86), 0.85 (95% CI: 0.73-0.93), 24 (95% CI: 9-65), 5.5 (95% CI: 2.8-10.8) and 0.23 (95% CI: 0.15-0.35), respectively. The AUC was 0.86 (95% CI: 0.83-0.89). The meta-analysis carried out in this report suggests that the I-FABP may be a useful diagnostic tool to confirm acute intestinal ischemia in acute abdomen, but better-designed trials are still required to confirm our findings. PMID- 27681958 TI - Confocal reference free traction force microscopy. AB - The mechanical wiring between cells and their surroundings is fundamental to the regulation of complex biological processes during tissue development, repair or pathology. Traction force microscopy (TFM) enables determination of the actuating forces. Despite progress, important limitations with intrusion effects in low resolution 2D pillar-based methods or disruptive intermediate steps of cell removal and substrate relaxation in high-resolution continuum TFM methods need to be overcome. Here we introduce a novel method allowing a one-shot (live) acquisition of continuous in- and out-of-plane traction fields with high sensitivity. The method is based on electrohydrodynamic nanodrip-printing of quantum dots into confocal monocrystalline arrays, rendering individually identifiable point light sources on compliant substrates. We demonstrate the undisrupted reference-free acquisition and quantification of high-resolution continuous force fields, and the simultaneous capability of this method to correlatively overlap traction forces with spatial localization of proteins revealed using immunofluorescence methods. PMID- 27681960 TI - Diabetes management - keeping up to date. PMID- 27681962 TI - The possible risks of proton pump inhibitors. PMID- 27681963 TI - Biosimilars in inflammatory bowel disease. PMID- 27681964 TI - No Jab, No Pay - no planning for migrant children. PMID- 27681965 TI - Central retinal venous pulsations. PMID- 27681966 TI - Neurofibromatosis of the tongue. PMID- 27681967 TI - Oral health: an important consideration in patient care. PMID- 27681969 TI - Being good. PMID- 27681968 TI - A medical student's first experience of theatre. PMID- 27681970 TI - Irritable bowel syndrome, dyspepsia and other chronic disorders of gastrointestinal function. PMID- 27681971 TI - The prevalence and clinical associations of HTLV-1 infection in a remote Indigenous community. AB - OBJECTIVE: Hospital and laboratory data indicate that human T-lymphotropic virus type 1 (HTLV-1) is endemic to central Australia, but no community-based studies of its prevalence or disease burden have been reported. We determined the prevalence rates of HTLV-1 infection and of HTLV-1-associated diseases in a remote Indigenous community. SETTING: A remote Northern Territory community. DESIGN: All residents were asked to complete a health survey and offered a limited clinical examination, together with serological tests for HTLV-1 and Strongyloides, and HTLV-1 proviral load (PVL) assessment. MAIN OUTCOME MEASURES: HTLV-1 seropositivity rates; HTLV-1 PVL (copies/105 peripheral blood leucocytes [PBL]); presentation with HTLV-1-related clinical disease. RESULTS: HTLV-1 serostatus was determined for 97 of 138 residents (70%). The prevalence of HTLV-1 infection was significantly higher among adults (30 of 74 people tested) than children (1 of 23; P = 0.001). Nine of 30 HTLV-1-positive adults had a clinical syndrome that was potentially attributable to HTLV-1 infection (chronic lung disease, seven; symptomatic strongyloidiasis, two). The median HTLV-1 PVL was significantly higher for adults with chronic lung disease than for those who were asymptomatic (chronic lung disease, 649 copies/105 PBL [IQR, 162-2220]; asymptomatic adults, 40 copies/105 PBL [IQR, 0.9-229]; P = 0.017). Ten of 72 adults tested were seropositive for Strongyloides (six of 28 HTLV-1-positive participants and four of 44 HTLV-1-negative participants; P = 0.17), as were three of 15 children tested; the three children were HTLV-1-negative. CONCLUSION: The prevalence of HTLV-1 infection and the rate of disease potentially attributable to HTLV-1 were high among adults in this remote community. PMID- 27681972 TI - Microgeographic factors and patterns of aeroallergen sensitisation. AB - OBJECTIVE: To examine patterns of airborne allergen (aeroallergen) sensitisation in the Greater Sydney area (Sydney), and their relationships with climate, coastal proximity and environment (urban v regional). DESIGN, SETTING, PARTICIPANTS: Retrospective cross-sectional study of patients who underwent aeroallergen skin prick testing at three Sydney allergy clinics, January 2001 - October 2014. MAIN OUTCOME MEASUREMENTS: Proportions of patients sensitised to specific aeroallergen types; relationships between sensitisation patterns and climate and geography. RESULTS: Of 1421 patients who met the selection criteria (mean age, 28.3 years [SD, 21.3]; 53.3% were female), 1092 (76.8%) were sensitised to at least one aeroallergen. Those living less than 15 km from the coast were less commonly sensitised to cockroach (< 15 km, 15.1%; 15-30 km, 40.0%; > 30 km, 39.7%; P < 0.001) and grass aeroallergens (< 15 km, 36.5%; 15-30 km, 52.2%; > 30 km, 58.1%; P < 0.001) than patients further inland; the same applied to mould, weed and tree aeroallergens. Subtropical grass sensitisation was more common in temperate/warm summer climates (about 50%) than in temperate/hot summer (27.1%) or subtropical climates (15%) (P < 0.001), and less common in urban (36.7%) than in regional areas (54%; P = 0.014). 72.4% of grass sensitised patients were co-sensitised to both temperate and subtropical grasses. A selected ten-aeroallergen skin prick test panel identified 98.5% of atopic patients in this Sydney sample. CONCLUSIONS: Environmental and geographic factors are associated with different patterns of allergic sensitisation in Sydney. Extensive co-sensitisation to subtropical and temperate grasses has implications for immunotherapy in Australia, where most currently available therapies are based on formulations directed at temperate grasses only. PMID- 27681973 TI - Gluten content of imported gluten-free foods: national and international implications. PMID- 27681974 TI - Barrett's oesophagus: epidemiology, diagnosis and clinical management. AB - Barrett's oesophagus is a condition characterised by partial replacement of the normal squamous epithelium of the lower oesophagus by a metaplastic columnar epithelium containing goblet cells (intestinal metaplasia). Barrett's oesophagus is important clinically because those afflicted are predisposed to oesophageal adenocarcinoma. Prevalence surveys suggest that up to 2% of the population may be affected; most will be unaware of their diagnosis. Risk factors include age, male sex, gastro-oesophageal acid reflux, central obesity and smoking. Helicobacter pylori infection confers a reduced risk of Barrett's oesophagus. Risks of cancer progression are lower than originally reported and are now estimated at 1-3 per 1000 patient-years for patients with non-dysplastic Barrett's oesophagus. Progression rates are higher for patients with long segment (>= 3 cm) and dysplastic Barrett's oesophagus. Australian guidelines have been developed to aid practitioners in managing patients with Barrett's oesophagus and early oesophageal adenocarcinoma. While generalised population screening for Barrett's oesophagus is not recommended, endoscopic surveillance of patients with confirmed Barrett's oesophagus is recommended, with surveillance intervals dependent on segment length and presence of dysplasia. New techniques such as endoscopic mucosal resection and endoscopic radiofrequency ablation are now available to treat patients with dysplasia and early oesophageal adenocarcinoma. New screening and surveillance technologies are currently under investigation; these may prove cost-effective in identifying and managing patients in the community. PMID- 27681975 TI - Primary amoebic meningoencephalitis in North Queensland: the paediatric experience. AB - Primary amoebic meningoencephalitis (PAM) is a fulminant, diffuse haemorrhagic meningoencephalitis caused by Naegleria fowleri, with an almost invariably fatal outcome. In Australia and the developed world, PAM remains a rare disease, although it is very likely that large numbers of cases go undetected in developing countries. N. fowleri is a thermophilic, free-living amoeba with a worldwide distribution. It is acquired when contaminated fresh water is flushed into the nose and penetrates the central nervous system via the cribriform plate. Clinical features are similar to those of bacterial meningitis, but it does not respond to standard therapy and rapid progression to death occurs in most cases. Some survivors have been reported; these patients received early treatment with amphotericin B in combination with a variety of other medications. Our review describes the local and worldwide experience of this disease and its clinical features, and discusses the associated diagnostic challenges. We hope that by detailing the local response to a recent case, and the outcomes of our public health campaign, we can improve the knowledge of this rare disease for doctors working in rural and remote Australia. PMID- 27681976 TI - Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's ageing population? AB - The incidence of type 2 diabetes is increasing in Australia's older adult population. Sarcopenia, the age-related decline in skeletal muscle mass, quality and function, may make a significant but under-appreciated contribution to increasing the risk of type 2 diabetes. As skeletal muscle is the largest insulin sensitive tissue in the body, low muscle mass in sarcopenia likely results in reduced capacity for glucose disposal. Age-related declines in muscle quality, including increased mitochondrial dysfunction and fat infiltration, are also implicated in skeletal muscle inflammation and subsequent insulin resistance. Prospective studies have shown that low muscle mass and strength are associated with increased risk of incident type 2 diabetes. Prevalent type 2 diabetes also appears to exacerbate progression of sarcopenia in older adults. Recently developed operational definitions and the inclusion of sarcopenia in the International classification of diseases, 10th revision, clinical modification, provide impetus for clinicians to diagnose and treat sarcopenia in older patients. Simple assessments to diagnose sarcopenia can potentially play a role in primary and secondary prevention of type 2 diabetes in older patients. Lifestyle modification programs for older adults with type 2 diabetes, particularly for those with sarcopenia, should incorporate progressive resistance training, along with adequate intakes of protein and vitamin D, which may improve both functional and metabolic health and prevent undesirable decreases in muscle mass associated with weight loss interventions. As some older adults with type 2 diabetes have a poor response to exercise, clinicians must ensure that lifestyle modification programs are appropriately prescribed, regularly monitored and modified if necessary. PMID- 27681977 TI - Using opioids in general practice for chronic non-cancer pain: an overview of current evidence. PMID- 27681978 TI - Using opioids in general practice for chronic non-cancer pain: an overview of current evidence. PMID- 27681979 TI - Using opioids in general practice for chronic non-cancer pain: an overview of current evidence. PMID- 27681980 TI - Surgical management of low back pain. PMID- 27681981 TI - Leslie Cowlishaw (1877-1943): the "bibliophile from the bush". PMID- 27681982 TI - How are tobacco smokers using e-cigarettes? Patterns of use, reasons for use and places of purchase in New South Wales. PMID- 27681983 TI - How are tobacco smokers using e-cigarettes? Patterns of use, reasons for use and places of purchase in New South Wales. PMID- 27681984 TI - Are we optimising outcomes in Australia's framework for the supply of plasma derived medicines? PMID- 27681985 TI - Synthesis, Properties, and Light-Emitting Electrochemical Cell (LEEC) Device Fabrication of Cationic Ir(III) Complexes Bearing Electron-Withdrawing Groups on the Cyclometallating Ligands. AB - The structure-property relationship study of a series of cationic Ir(III) complexes in the form of [Ir(C^N)2(dtBubpy)]PF6 [where dtBubpy = 4,4'-di-tert butyl-2,2'-bipyridine and C^N = cyclometallating ligand bearing an electron withdrawing group (EWG) at C4 of the phenyl substituent, i.e., -CF3 (1), -OCF3 (2), -SCF3 (3), -SO2CF3 (4)] has been investigated. The physical and optoelectronic properties of the four complexes were comprehensively characterized, including by X-ray diffraction analysis. All the complexes exhibit quasireversible dtBubpy-based reductions from -1.29 to -1.34 V (vs SCE). The oxidation processes are likewise quasireversible (metal + C^N ligand) and are between 1.54 and 1.72 V (vs SCE). The relative oxidation potentials follow a general trend associated with the Hammett parameter (sigma) of the EWGs. Surprisingly, complex 4 bearing the strongest EWG does not adhere to the expected Hammett behavior and was found to exhibit red-shifted absorption and emission maxima. Nevertheless, the concept of introducing EWGs was found to be generally useful in blue-shifting the emission maxima of the complexes (lambdaem = 484-545 nm) compared to that of the prototype complex [Ir(ppy)2(dtBubpy)]PF6 (where ppy = 2-phenylpyridinato) (lambdaem = 591 nm). The complexes were found to be bright emitters in solution at room temperature (PhiPL = 45-66%) with microsecond excited-state lifetimes (taue = 1.14-4.28 MUs). The photophysical properties along with density functional theory (DFT) calculations suggest that the emission of these complexes originates from mixed contributions from ligand-centered (LC) transitions and mixed metal-to-ligand and ligand-to-ligand charge transfer (LLCT/MLCT) transitions, depending on the EWG. In complexes 1, 3, and 4 the 3LC character is prominent over the mixed 3CT character, while in complex 2, the mixed 3CT character is much more pronounced, as demonstrated by DFT calculations and the observed positive solvatochromism effect. Due to the quasireversible nature of the oxidation and reduction waves, fabrication of light-emitting electrochemical cells (LEECs) using these complexes as emitters was possible with the LEECs showing moderate efficiencies. PMID- 27681987 TI - Application of Microextraction Techniques Including SPME and MESI to the Thermal Degradation of Polymers: A Review. AB - Here, we discuss the newly developed micro and solventless sample preparation techniques SPME (Solid Phase Microextraction) and MESI (Membrane Extraction with a Sorbent Interface) as applied to the qualitative and quantitative analysis of thermal oxidative degradation products of polymers and their stabilizers. The coupling of these systems to analytical instruments is also described. Our comprehensive literature search revealed that there is no previously published review article on this topic. It is shown that these extraction techniques are valuable sample preparation tools for identifying complex series of degradation products in polymers. In general, the number of products identified by traditional headspace (HS-GC-MS) is much lower than with SPME-GC-MS. MESI is particularly well suited for the detection of non-polar compounds, therefore number of products identified by this technique is not also to the same degree of SPME. Its main advantage, however, is its ability of (semi-) continuous monitoring, but it is more expensive and not yet commercialized. PMID- 27681986 TI - Age-dependent impact of inferior alveolar nerve transection on mandibular bone metabolism and the underlying mechanisms. AB - Aging is associated with peripheral nerve degradation and bone destruction. The aim of the study is to elucidate the influence of sensory denervation on bone metabolism in different age groups by establishing a modified unilateral inferior alveolar nerve transection (IANT) model. The rats, divided into young, middle aged and aged group, were sacrificed at 1, 2, 4 and 8 weeks after right IANT. The histological changes of mandibles were analyzed by fluorescent double labeling, micro-CT, HE, TRAP and anti-CGRP immunohistochemical staining. Molecular mechanisms underlying the changes were analyzed by qPCR and western blot. Differences between the test and control side were evaluated by paired-samples t test. The Friedman test and separate Wilcoxon signed-rank tests were applied to analyze age-dependent difference. The impact of IANT was the most intensive in developing bone, the most persistent in full grown bone and the faintest in the aged bone. The role of IAN in keeping homeostasis was closely related to the anabolic effect of CGRP, which suppressed the number of osteoclasts through OPG/RANKL ratio and controlled growth factors expression like BMP2. This study contributes to a better understanding of the molecular mechanisms of CGRP in vivo and the relationship among sensory nerve, bone metabolism and aging. PMID- 27681988 TI - Using Discrete Choice Experiments with Duration to Model EQ-5D-5L Health State Preferences. AB - BACKGROUND: Discrete choice experiments incorporating duration can be used to derive health state values for EQ-5D-5L. Yet, methodological issues relating to the duration attribute and the optimal way to select health states remain. The aims of this study were to: test increasing the number of duration levels and choice sets where duration varies (aim 1); compare designs with zero and non-zero prior values (aim 2); and investigate a novel, two-stage design to incorporate prior values (aim 3). METHODS: Informed by zero and non-zero prior values, two efficient designs were developed, each consisting of 120 EQ-5D-5L health profile pairs with one of six duration levels (aims 1 and 2). Another 120 health state pairs were selected, with one of six duration levels allocated in a second stage based on existing estimated utility of the states (aim 3). An online sample of 2,002 members of the UK general population completed 10 choice sets each. Differences across the regression coefficients from the three designs were assessed. RESULTS: The zero prior value design produced a model with coefficients that were generally logically ordered, but the non-zero prior value design resulted in a set of less ordered coefficients where some differed significantly. The two-stage design resulted in ordered and significant coefficients. The non zero prior value design may include more "difficult" choice sets, based on the proportions choosing each profile. CONCLUSIONS: There is some indication of compromised "respondent efficiency", suggesting that the use of non-zero prior values will not necessarily result in better overall precision. It is feasible to design discrete choice experiments in two stages by allocating duration values to EQ-5D-5L health state pairs based on estimates from prior studies. PMID- 27681989 TI - Understanding the Effects of Competition for Constrained Colonoscopy Services with the Introduction of Population-level Colorectal Cancer Screening. AB - BACKGROUND: Median wait times for gastroenterology services in Canada exceed consensus-recommended targets and have worsened substantially over the past decade. Meanwhile, efforts to control colorectal cancer have shifted their focus to screening asymptomatic, average-risk individuals. Along with increasing prevalence of colorectal cancer due to an aging population, screening programs are expected to add substantially to the existing burden on colonoscopy services, and create competition for limited services among individuals of varying risk. Failure to understand the effects of operational programmatic screening decisions may cause unintended harm to both screening participants and higher-risk patients, make inefficient use of limited health care resources, and ultimately hinder a program's success. METHODS: We present a new simulation model (Simulation of Cancer Outcomes for Planning Exercises, or SCOPE) for colorectal cancer screening which, unlike many other colorectal cancer screening models, reflects the effects of competition for limited colonoscopy services between patient groups and can be used to guide planning to ensure adequate resource allocation. We include verification and validation results for the SCOPE model. RESULTS: A discrete event simulation model was developed based on an epidemiological representation of colorectal cancer in a sample population. Colonoscopy service and screening modules were added to allow observation of screening scenarios and resource considerations. The model reproduces population based data on prevalence of colorectal cancer by stage, and mortality by cause of death, age, and sex, and attendant demand and wait times for colonoscopy services. CONCLUSIONS: The study model differs from existing screening models in that it explicitly considers the colonoscopy resource implications of screening activities and the impact of constrained resources on screening effectiveness. PMID- 27681990 TI - Extrapolation of Survival Curves from Cancer Trials Using External Information. AB - BACKGROUND: Estimates of life expectancy are a key input to cost-effectiveness analysis (CEA) models for cancer treatments. Due to the limited follow-up in Randomized Controlled Trials (RCTs), parametric models are frequently used to extrapolate survival outcomes beyond the RCT period. However, different parametric models that fit the RCT data equally well may generate highly divergent predictions of treatment-related gain in life expectancy. Here, we investigate the use of information external to the RCT data to inform model choice and estimation of life expectancy. METHODS: We used Bayesian multi parameter evidence synthesis to combine the RCT data with external information on general population survival, conditional survival from cancer registry databases, and expert opinion. We illustrate with a 5-year follow-up RCT of cetuximab plus radiotherapy v. radiotherapy alone for head and neck cancer. RESULTS: Standard survival time distributions were insufficiently flexible to simultaneously fit both the RCT data and external data on general population survival. Using spline models, we were able to estimate a model that was consistent with the trial data and all external data. A model integrating all sources achieved an adequate fit and predicted a 4.7-month (95% CrL: 0.4; 9.1) gain in life expectancy due to cetuximab. CONCLUSIONS: Long-term extrapolation using parametric models based on RCT data alone is highly unreliable and these models are unlikely to be consistent with external data. External data can be integrated with RCT data using spline models to enable long-term extrapolation. Conditional survival data could be used for many cancers and general population survival may have a role in other conditions. The use of external data should be guided by knowledge of natural history and treatment mechanisms. PMID- 27681991 TI - Disclosing the Uncertainty Associated with Prognostic Estimates in Breast Cancer. AB - BACKGROUND: Treatment decision making is often guided by evidence-based probabilities, which may be presented to patients during consultations. These probabilities are intrinsically imperfect and embody 2 types of uncertainties: aleatory uncertainty arising from the unpredictability of future events and epistemic uncertainty arising from limitations in the reliability and accuracy of probability estimates. Risk communication experts have recommended disclosing uncertainty. We examined whether uncertainty was discussed during cancer consultations and whether and how patients perceived uncertainty. METHODS: Consecutive patient consultations with medical oncologists discussing adjuvant treatment in early-stage breast cancer were audiotaped, transcribed, and coded. Patients were interviewed after the consultation to gain insight into their perceptions of uncertainty. RESULTS: In total, 198 patients were included by 27 oncologists. Uncertainty was disclosed in 49% (97/197) of consultations. In those 97 consultations, 23 allusions to epistemic uncertainty were made and 84 allusions to aleatory uncertainty. Overall, the allusions to the precision of the probabilities were somewhat ambiguous. Interviewed patients mainly referred to aleatory uncertainty if not prompted about epistemic uncertainty. Even when specifically asked about epistemic uncertainty, 1 in 4 utterances referred to aleatory uncertainty. When talking about epistemic uncertainty, many patients contradicted themselves. In addition, 1 in 10 patients seemed not to realize that the probabilities communicated during the consultation are imperfect. CONCLUSIONS: Uncertainty is conveyed in only half of patient consultations. When uncertainty is communicated, oncologists mainly refer to aleatory uncertainty. This is also the type of uncertainty that most patients perceive and seem comfortable discussing. Given that it is increasingly common for clinicians to discuss outcome probabilities with their patients, guidance on whether and how to best communicate uncertainty is urgently needed. PMID- 27681992 TI - Sensitivity Analysis in Sequential Decision Models. AB - BACKGROUND: Sequential decision problems are frequently encountered in medical decision making, which are commonly solved using Markov decision processes (MDPs). Modeling guidelines recommend conducting sensitivity analyses in decision analytic models to assess the robustness of the model results against the uncertainty in model parameters. However, standard methods of conducting sensitivity analyses cannot be directly applied to sequential decision problems because this would require evaluating all possible decision sequences, typically in the order of trillions, which is not practically feasible. As a result, most MDP-based modeling studies do not examine confidence in their recommended policies. METHOD: In this study, we provide an approach to estimate uncertainty and confidence in the results of sequential decision models. RESULTS: First, we provide a probabilistic univariate method to identify the most sensitive parameters in MDPs. Second, we present a probabilistic multivariate approach to estimate the overall confidence in the recommended optimal policy considering joint uncertainty in the model parameters. We provide a graphical representation, which we call a policy acceptability curve, to summarize the confidence in the optimal policy by incorporating stakeholders' willingness to accept the base case policy. For a cost-effectiveness analysis, we provide an approach to construct a cost-effectiveness acceptability frontier, which shows the most cost-effective policy as well as the confidence in that for a given willingness to pay threshold. We demonstrate our approach using a simple MDP case study. CONCLUSIONS: We developed a method to conduct sensitivity analysis in sequential decision models, which could increase the credibility of these models among stakeholders. PMID- 27681993 TI - Response to Re: The end of emergency medicine as we know it. PMID- 27681995 TI - Dyspnoea in an older woman. PMID- 27681994 TI - Accumulation of heavy metals and trace elements in fluvial sediments received effluents from traditional and semiconductor industries. AB - Metal accumulation in sediments threatens adjacent ecosystems due to the potential of metal mobilization and the subsequent uptake into food webs. Here, contents of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) and trace elements (Ga, In, Mo, and Se) were determined for river waters and bed sediments that received sewage discharged from traditional and semiconductor industries. We used principal component analysis (PCA) to determine the metal distribution in relation to environmental factors such as pH, EC, and organic matter (OM) contents in the river basin. While water PCA categorized discharged metals into three groups that implied potential origins of contamination, sediment PCA only indicated a correlation between metal accumulation and OM contents. Such discrepancy in metal distribution between river water and bed sediment highlighted the significance of physical-chemical properties of sediment, especially OM, in metal retention. Moreover, we used Se XANES as an example to test the species transformation during metal transportation from effluent outlets to bed sediments and found a portion of Se inventory shifted from less soluble elemental Se to the high soluble and toxic selenite and selenate. The consideration of environmental factors is required to develop pollution managements and assess environmental risks for bed sediments. PMID- 27681996 TI - Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion. AB - The purpose of this study was to examine potential long-term post-torsion changes that can occur in the histopathology, biochemistry and spermatogenesis of both torsioned and nontorsioned opposite testes. The study also determines the effect of zinc (Zn) administration on the testicular torsion/detorsion (T/D) damage on both testes. Forty-eight male rats, divided equally into eight groups: (SHAM), (SHAM+,Zn+), (T/D+, Zn- 1 month), (T/D+,Zn- 2 months), (T/D+,Zn- 3 months), (T/D+,Zn+ 1 months), (T/D+,Zn+ 2 months), (T/D+,Zn+ 3 months), have been used. Drug administration was carried out by adding 100 MUg (0.016 ml/rat) Zn per rat to drinking water in related groups. Testicular damage decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in the testis tissues of rats, while Zn administration increased SOD and GSH and decreased MDA in the testis tissues in comparison with the SHAM group. The beneficial effect of zinc sulphate was more evident on the nonrotated testis than the rotated testis. In the histopathological study, a significant decrease in torsion and detorsion injuries was observed in the treatment groups compared to the torsion and detorsion groups. We found a protective effect of zinc sulphate on oxidative stress as a result of T/D injuries in rats, especially for the nonrotated testis; results were supported histopathologically. PMID- 27681998 TI - Proceedings SaskVal 2015. PMID- 27681997 TI - Molecular and clinical features of KATP -channel neonatal diabetes mellitus in Japan. AB - BACKGROUND: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). OBJECTIVES: To elucidate the characteristics of Japanese patients with KATP-NDM. METHODS: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. RESULTS: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. CONCLUSION: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms. PMID- 27681999 TI - Uterine, but not ovarian, female reproductive organ involvement at presentation by diffuse large B-cell lymphoma is associated with poor outcomes and a high frequency of secondary CNS involvement. AB - Involvement of the internal female reproductive organs by diffuse large B-cell lymphoma (DLBCL) is uncommon, and there are sparse data describing the outcomes of such cases. In total, 678 female patients with DLBCL staged with positron emission tomography/computed tomography and treated with rituximab-containing chemotherapy were identified from databases in Denmark, Great Britain, Australia, and Canada. Overall, 27/678 (4%) had internal reproductive organ involvement: uterus (n = 14), ovaries (n = 10) or both (n = 3). In multivariate analysis, women with uterine DLBCL experienced inferior progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system (CNS) involvement (SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL) and 0/10 women with ovarian DLBCL without concomitant uterine involvement. In multivariate analysis adjusted for other risk factors for SCNS, uterine involvement by DLBCL remained strongly associated with SCNS (Hazard ratio 14.13, 95% confidence interval 5.09-39.25, P < 0.001). Because involvement of the uterus by DLBCL appears to be associated with a high risk of SCNS, those patients should be considered for CNS staging and prophylaxis. However, more studies are needed to determine whether the increased risk of secondary CNS involvement also applies to women with localized reproductive organ DLBCL. PMID- 27682000 TI - Symptoms of post-traumatic stress disorder, severe psychological distress, explosive anger and grief amongst partners of survivors of high levels of trauma in post-conflict Timor-Leste. AB - BACKGROUND: Little is known about the mental health of partners of survivors of high levels of trauma in post-conflict countries. METHOD: We studied 677 spouse dyads (n = 1354) drawn from a community survey (response 82.4%) in post-conflict Timor-Leste. We used culturally adapted measures of post-traumatic stress disorder (PTSD), psychological distress, explosive anger and grief. RESULTS: Latent class analysis identified three classes of couples: class 1, comprising women with higher trauma events (TEs), men with intermediate TEs (19%); class 2, including men with higher TEs, women with lower TEs (23%); and class 3, comprising couples in which men and women had lower TE exposure (58%) (the reference group). Men and women partners of survivors of higher TE exposure (classes 1 and 2) had increased symptoms of explosive anger and grief compared with the reference class (class 3). Women partners of survivors of higher TE exposure (class 2) had a 20-fold increased rate of PTSD symptoms compared with the reference class, a pattern that was not evident for men living with women exposed to higher levels of trauma (class 1). CONCLUSIONS: Men and women living with survivors of higher levels of trauma showed an increase in symptoms of grief and explosive anger. The manifold higher rate of PTSD symptoms amongst women living with men exposed to high levels of trauma requires replication. It is important to assess the mental health of partners when treating survivors of high levels of trauma in post-conflict settings. PMID- 27682002 TI - Oxidized LDL, insulin resistance and central blood pressure after gestational diabetes mellitus. AB - INTRODUCTION: Gestational diabetes mellitus (GDM) is an indicator of future cardiovascular disease. We investigated whether sensitive biomarkers of increased cardiovascular risk differ between women with and without a history of GDM few years after pregnancy, and whether obesity affects the results. MATERIAL AND METHODS: We studied two cohorts - 120 women with a history of GDM and 120 controls, on average 3.7 years after delivery. Circulating concentrations of oxidized low-density lipoprotein (oxLDL) were determined by ELISA. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to estimate insulin resistance. Central blood pressure (cBP) was measured noninvasively from a radial artery pulse wave. The primary outcomes were possible differences in oxLDL, HOMA-IR or cBP between the groups. Secondly, we investigated the influence of obesity on the results, also using adjusted multiple linear regression analyses. RESULTS: OxLDL concentrations or cBP did not differ between the two cohorts, but HOMA-IR was significantly higher in women with previous GDM than in controls, 1.3 +/- 0.9 (SD) and 1.1 +/- 0.9, respectively (p = 0.022). In subgroup analyses, HOMA-IR (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) cBP were significantly higher in obese subgroups compared with non-obese ones. Body mass index was an important determinant of HOMA-IR and cBP in multiple linear regression analyses. CONCLUSIONS: Over 3 years after delivery, women with GDM were still more insulin resistant than controls. Obesity turned out to be a more important determinant of insulin resistance and cBP compared with GDM. PMID- 27682003 TI - cTnI Exacerbates Myocardial Ischemia/Reperfusion Injury by Inducing Adhesion of Monocytes to VECs via TLR4/NF-kappaB-dependent Pathway. AB - Cardiac troponin I (cTnI), a biomarker for myocardial damage and risk stratification, may be involved in the pathogenesis of cardiovascular diseases, which was ascribed to the effect of cTnI auto-antibodies. Whether or not cTnI itself has a direct impact on acute myocardial injury is unknown. To exclude the influence of cTnI antibody on the cardiac infarct size, we studied the effect of cTnI shortly after myocardial ischemia-reperfusion (I/R) injury when cTnI antibodies were not elevated. Pretreatment with cTnI augmented the myocardial infarct size caused by I/R, accompanied by an increase in inflammatory markers in the blood and myocardium. Additional experiments using human umbilical vein endothelial cells (HUVECs) showed that the detrimental effect of cTnI was related to cTnI-induced increase in VCAM-1 expression and VCAM-1 mediated adhesion of human monocytes (THP-1) to HUVECs, which could be neutralized by VCAM-1 antibody. Both toll-like receptor 4 (TLR4) and NF-kappaB were involved in the signaling pathway, because blockade of either TLR4 or NF-kappaB inhibited the cTnI's effect on VCAM-1 expression and adhesion of monocytes to endothelial cells. Moreover, TLR4 inhibition reduced cTnI-augmented cardiac injury in rats with I/R injury. We conclude that cTnI exacerbates myocardial I/R injury by inducing the adhesion of monocytes to vascular endothelial cells via activation of the TLR4/NF-kappaB pathway. Inhibition of TLR4 may be an alternative strategy to reduce cTnI-induced myocardial I/R injury. PMID- 27682001 TI - Association between perfluorooctanoic acid exposure and degranulation of mast cells in allergic inflammation. AB - Perfluorooctanoic acid (PFOA) has wide applications, including as a raw material for converted paper and packaging products. With the widespread use of PFOA, concerns regarding its potential environmental and health impacts have increased. In spite of the known hepatotoxicity and genotoxicity of PFOA, correlation with PFOA and allergic inflammation is not well known. In this study, the effect of PFOA on the degranulation of mast cells and mast cell-mediated allergic inflammation in the presence of FcepsilonRI cross-linking was evaluated. In immunoglobulin (Ig) E-stimulated mast cells, PFOA increased the release of histamine and beta-hexosaminidase by the up-regulation of intracellular calcium levels. PFOA enhanced gene expression of several pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL 8 by the activation of nuclear factor (NF)-kappaB in IgE-stimulated mast cells. Also, PFOA exacerbated allergic symptoms via hypothermia, and an increase of serum histamine, TNF-alpha, IgE and IgG1 in the ovalbumin-induced systemic anaphylaxis. The present data indicate that PFOA aggravated FcERI-mediated mast cell degranulation and allergic symptoms. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27682004 TI - Nonconsecutive versus consecutive-day resistance training in recreationally trained subjects. AB - BACKGROUND: Previous studies have shown that total-body resistance training (RT) performed two to three alternating days per week has positive effects on muscle strength and body composition. However, no evidence exists to determine if total body RT workouts done on consecutive days (CD) are beneficial. Therefore, the purpose of this study was to compare the effects of a total-body RT program performed on three consecutive or nonconsecutive days (NCD) per week for 7 weeks on maximum strength and body composition in recreationally trained subjects. METHODS: Twenty-one men were randomly assigned to a 3NCD (N.=11) or 3CD group (N.=10). Prior and following training, anthropometric measures, and 1 repetition maximum values for leg press, and bench press were measured. RESULTS: Statistical analysis revealed a significant increase for leg press strength and bench press strength for both groups (P<0.01) from pre to post intervention. There was also a significant increase for arm and chest girth measures (P<0.05) on the 3 CD group. No significant differences between groups were observed. CONCLUSIONS: The results suggest that RT programs performed on three consecutive or nonconsecutive days per week determine similar effects on maximum strength, and body composition. PMID- 27682007 TI - Hierarchical Self-Assembly of Luminescent Tartrate-Bridged Chiral Binuclear Tb(III) Complexes in Ethanol. AB - A new family of supramolecular metalloamphiphiles carrying two metal centers is developed. They are formed by bridging two coordinatively unsaturated lipophilic Tb3+ complexes (TbL+) with chiral dicarboxylate anions. The formation of bridging coordination bonds is confirmed using UV spectroscopy, induced circular dichroism (ICD), increased luminescence intensity of TbL+, and electrospray ionization mass spectrometry (ESIMS) analysis. These supramolecular metalloamphiphiles hierarchically self-assemble in ethanol to give luminescent nanospheres, as observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The two hydroxyl groups introduced in the bridging ligands of [TbL]2(d-/l-tartrate) significantly promote self-assembly by increasing coherent forces via intermolecular hydrogen bonding. The observed self-assembly in ethanol also merits mention because such polar alcoholic media have been unfavorable for conventional molecular self-assemblies. The present approach offers a new molecular design strategy for composable metalloamphiphiles. PMID- 27682006 TI - Allogeneic Blood Transfusion Is a Significant Risk Factor for Surgical-Site Infection Following Total Hip and Knee Arthroplasty: A Meta-Analysis. AB - BACKGROUND: Blood loss occurs significantly more frequently during total hip and knee arthroplasty than among any other type of orthopedic operation, which can sometimes lead to requiring a blood transfusion. Although allogeneic blood transfusion has been identified as a risk factor for postoperative surgical-site infection following arthroplasty, results are inconclusive. The purpose of this study was to conduct a systematic meta-analysis to investigate whether having an allogeneic blood transfusion significantly increases the risk for surgical-site infection, particularly after total hip and knee arthroplasty. METHODS: We performed a systematic review and meta-analysis using random-effect models. Using an electronic database search, we selected 6 studies that included data on 21,770 patients and among these studies compared the postoperative infection rate between an allogeneic blood-transfusion exposure group and a nonexposure group. We calculated the pooled odds ratios and 95% confidence intervals for the groups. RESULTS: The prevalences of surgical-site infections in our pooled analyses were 2.88% and 1.74% for the transfusion and nontransfusion groups, respectively. The allogeneic blood transfusion group had a significantly higher frequency of surgical-site infections based on pooled analysis using a random-effect model (pooled odds ratio = 1.71, 95% confidence interval: 1.23-2.40, P = .002). CONCLUSION: Allogeneic blood transfusion is a significant risk factor for increasing the surgical-site infection rate after total hip and knee arthroplasty. PMID- 27682005 TI - Late Complications Following Elective Primary Total Hip and Knee Arthroplasty: Who, When, and How? AB - BACKGROUND: Improved pain management and early mobilization protocols have increased interest in the feasibility of short stay (<24 hours) or outpatient total hip (THA) and total knee (TKA) arthroplasty. However, concerns exist regarding patient safety and readmissions. The purposes of this study were to determine the incidence of in-hospital complications following THA/TKA, to create a model to identify comorbidities associated with the risk of developing major complications >24 hours postoperatively, and to validate this model against another consecutive series of patients. METHODS: We prospectively evaluated a consecutive series of 802 patients who underwent elective primary THA and TKA over a 9-month period. The mean age was 62.3 years. Demographic, surgical, and postoperative readmission data were entered into an arthroplasty database. RESULTS: Of the 802 patients, 382 experienced a complication postoperatively. Of these, 152 (19%) required active management. Multiple logistic regression analysis identified cirrhosis (odds ratio [OR], 5.89; 95% confidence interval [CI], 1.05-33.07; P = .044), congestive heart failure (OR, 3.12; 95% CI, 1.50 6.44; P = .002), and chronic kidney disease (OR, 3.85; 95% CI, 2.21-6.71; P < .001) as risk factors for late complications. One comorbidity was associated with a 77% probability of developing a major postoperative complication. This model was validated against an independent dataset of 1012 patients. CONCLUSION: With improved pain management and mobilization protocols, there is increasing interest in short stay and outpatient THA and TKA. Patients with cirrhosis, congestive heart failure, or chronic kidney disease should be excluded from early discharge total joint arthroplasty protocols. PMID- 27682009 TI - Density Functional Study of Stacking Structures and Electronic Behaviors of AnE PV Copolymer. AB - In this work, we report an in-depth investigation on the pi-stacking and interdigitating structures of poly(p-anthracene-ethynylene)-alt-poly(p-phenylene vinylene) copolymer with octyl and ethyl-hexyl side chains and the resulting electronic band structures using density functional theory calculations. We found that in the pi-stacking direction, the preferred stacking structure, determined by the steric effect of the branched ethyl-hexyl side chains, is featured by the anthracene-ethynylene units stacking on the phenylene-vinylene units of the neighboring chains and vice versa. This stacking structure, combined with the interdigitating structure where the branched side chains of the laterally neighboring chains are isolated, defines the energetically favorable structure of the ordered copolymer phase, which provides a good compromise between light absorption and charge-carrier transport. PMID- 27682008 TI - The Sewol Ferry Disaster: Experiences of a Community-Based Hospital in Ansan City. AB - The Sewol ferry disaster is one of the most tragic events in Korea's modern history. Among the 476 people on board, which included Danwon High School students (324) and teachers (14), 304 passengers died in the disaster (295 recovered corpses and 9 missing) and 172 survived. Of the rescued survivors, 72 were attending Danwon High School, located in Ansan City, and residing in a residence nearby. Because the students were young, emotionally susceptible adolescents, both the government and the parents requested the students be grouped together at a single hospital capable of appropriate psychiatric care. Korea University Ansan Hospital was the logical choice, as the only third-tier university-grade hospital with the necessary faculty and facilities within the residential area of the families of the students. We report the experiences and the lessons learned from the processes of preparing for and managing the surviving young students as a community-based hospital. (Disaster Med Public Health Preparedness. 2017;11:389-393). PMID- 27682010 TI - Copper-Catalyzed Hydroxylation of (Hetero)aryl Halides under Mild Conditions. AB - The combination of Cu(acac)2 and N,N'-bis(4-hydroxyl-2,6-dimethylphenyl)oxalamide (BHMPO) provides a powerful catalytic system for hydroxylation of (hetero)aryl halides. A wide range of (hetero)aryl chlorides bearing either electron-donating or -withdrawing groups proceeded well at 130 degrees C, delivering the corresponding phenols and hydroxylated heteroarenes in good to excellent yields. When more reactive (hetero)aryl bromides and iodides were employed, the hydroxylation reactions completed at relatively low temperatures (80 and 60 degrees C, respectively) at low catalytic loadings (0.5 mol % Cu). PMID- 27682011 TI - The T>A (rs11646213) gene polymorphism of cadherin-13 (CDH13) gene is associated with decreased risk of developing hypertension in Mexican population. AB - Hypertension is a major public health problem affecting about 30% of the adult population and is associated with an increased risk of developing metabolic and cardiovascular disease. Recent reports have shown that the T-cadherin receptor characteristically expressed on endothelial and vascular smooth muscle cells is involved in hypertension. The aim of the present study was to evaluate the role of cadherin-13 (CDH13) gene polymorphisms as susceptibility markers for hypertension in Mexican population. Six CDH13 polymorphisms (rs11646213, rs11646411, rs6563943, rs3096277, rs3784990 and rs254340) were genotyped by 5' exonuclease TaqMan assays in a group of 644 hypertensive and 765 non-hypertensive individuals. Under co-dominant, recessive, and additive models, the CDH13 T>A (rs11646213) polymorphism was associated with decreased risk of developing hypertension when compared to non-hypertensive individuals (OR=0.61, 95% CI: 0.42 0.89, Pco-dom=0.019; OR=0.63, 95% CI: 0.46-0.87, Pres=0.005; OR=0.80, 95% CI: 0.66-0.96, Padd=0.016, respectively). All models were adjusted by gender, age, body index mass, type II diabetes mellitus, alcohol consumption, dyslipidemia and smoking habit. Linkage disequilibrium analysis showed one haplotype (TCACGG) with decreased frequency in hypertensive when compared to non-hypertensive individuals (OR=0.52, 95% CI: 0.33-0.82, P=0.0053). In summary, our data suggests that the CDH13 T>A (rs11646213) polymorphism is associated with decreased risk of developing hypertension in the Mexican population. In addition, it was possible to distinguish one haplotype associated with decreased risk and two for increased risk of develop hypertension. PMID- 27682012 TI - Dipeptidyl peptidase 9 (DPP9) in human skin cells. AB - BACKGROUND: Dipeptidyl peptidase 9 (DPP9) is a relatively new member of the DPPIV family of prolyl dipeptidases which is ubiquitously expressed. Its role in regulation of immune responses and proliferation of epithelial carcinoma cells was reported. There is no data on possible role of DPP9 expressed in skin epithelial cells (keratinocytes) and in dermal fibroblasts. MATERIALS AND METHODS: Transcriptional and protein expression of DPP9 and DPPIV was examined in fibroblasts and keratinocytes isolated from normal human skin. Localization of DPP9 and its sub-localization in Golgi were determined by immunocytochemistry staining. DPPIV-like enzyme activity was determined in cell lysates and in isolated cell fractions containing membranes (M), cytosol (C) and content of organelles/endosomes/vesicles (V). Relative contribution of DPPIV and DPP8/9 enzyme activity in these fractions was determined by using selective inhibitors: sitagliptin (selective for DPPIV) and 1G244 (selective for DPP9 and a highly homologous DPP8). Possible roles of DPP8/9 via its enzyme activity were analysed by assessment of survival and proliferative capacity of fibroblasts and HaCaT cells of keratinocyte origin in the presence of the inhibitors. Possible role of DPP9 in cell migration and/or adhesion was analysed in fibroblasts and HaCaT cells after DPP9 gene silencing. RESULTS: Fibroblasts and keratinocytes exerted comparable level of DPP9 both at transcriptional and protein level. Fibroblasts strongly expressed DPPIV, whereas in keratinocytes DPPIV expression was low. DPP9 expression was found in cytosol and in perinuclear area of some fibroblasts, or in scattered pattern of keratinocytes, as well as in nuclei of some cells. Only low level of DPP9 sub-localization within Golgi was observed in fibroblasts and keratinocytes. DPPIV-like enzyme activity was about 5 times higher in lysates of fibroblasts than of HaCaT cells. In fibroblasts DPPIV-like enzyme activity was mainly (65%) found in the fraction containing cell membranes (M) and was predominantly (86.9%) due to DPPIV. In contrast, in HaCaT cells the DPPIV-like enzyme activity was mainly (84.2%) found in cytosol (C) and was predominantly (95.6%) due to DPP8/9. Survival and the proliferative capacity were significantly diminished in the presence of 10MUM 1G244, both in fibroblasts and in HaCaT cells, suggesting possible role of DPP8/9 enzyme activity in regulation of survival and proliferation of these cells. DPP9 gene silencing resulted in decreased adhesion of fibroblasts, as well as in decreased migration of fibroblasts and HaCaT cells. Accumulation of DPP9 on the edges of plasma membranes of fibroblasts and keratinocytes adhering to surface supports the idea of possible role of DPP9 in cell adhesion. CONCLUSIONS: This is the first study showing protein expression, sub-localization and possible biological roles of DPP9 expressed in isolated human skin cells. The data may be relevant for development of new drugs against skin diseases by targeting DPP9 expressed in the skin cells. PMID- 27682013 TI - Regulation of Siglec-8-induced intracellular reactive oxygen species production and eosinophil cell death by Src family kinases. AB - RATIONALE: Siglec-8 is a surface receptor predominantly expressed on human eosinophils where its ligation induces reactive oxygen species (ROS) formation and cell death. Since Siglec-8 has intracellular tyrosine-based motifs, we hypothesized that Src family kinases (SFKs) are involved in ROS formation and cell death induced by Siglec-8 engagement. METHODS: Human peripheral blood eosinophils were purified and incubated with anti-Siglec-8 monoclonal antibodies (mAb, agonist), IL-5, and SFK pharmacological inhibitors. We focused on Siglec-8 induced cell death in short-term IL-5-activated cells leading to a regulated necrosis-type cell death. ROS production was determined by dihydrorhodamine (DHR) 123 labeling and flow cytometry, or by chemiluminescence using Amplex red. Activation of SFK was determined using phospholuminex and Western blotting. RESULTS: In order to determine cellular localization of ROS production, we measured intra and extracellular ROS. While an ETosis stimulus (calcium ionophore A23187) led to extracellular ROS (ecROS) production, Siglec-8-engagement in short term IL-5 activated cells led to intracellular ROS (icROS) accumulation. Consistently, inhibition of extracellular ROS by catalase inhibited ETosis, but not IL-5-primed Siglec-8-induced cell death. In order to determine signaling events for Siglec-8, we performed Western blotting and found SFK phosphorylation in lysates from eosinophils stimulated with anti-Siglec-8 mAb+/-IL-5. In order to identify which SFKs were involved, we used the phospholuminex assay and found increased levels of phosphorylated Fgr in the cytoplasmic fraction of cells co stimulated with anti-Siglec-8 and IL-5 for 3 hours compared with cells stimulated with IL-5 alone. To test the involvement of SFKs in ROS production and cell death, we used SFK inhibitors PP2 and dasatinib, both of which completely inhibited eosinophil ROS production and cell death induced by anti-Siglec-8 and IL-5 co-stimulation. CONCLUSION: Siglec-8 engagement in short-term IL-5-activated eosinophils causes icROS production and SKF phosphorylation, and both are essential in mediating Siglec-8-induced cell death. PMID- 27682014 TI - Visualization of Neutrophil Extracellular Traps and Fibrin Meshwork in Human Fibrinopurulent Inflammatory Lesions: I. Light Microscopic Study. AB - Neutrophil extracellular traps (NETs) are extracellular fibrillary structures composed of degraded chromatin and granules of neutrophil origin. In fibrinopurulent inflammation such as pneumonia and abscess, deposition of fibrillar eosinophilic material is a common histopathological finding under hematoxylin-eosin staining. Expectedly, not only fibrin fibrils but also NETs consist of the fibrillar material. The aim of the present study is to analyze immunohistochemically how NETs are involved in the inflammatory process. Archival formalin-fixed, paraffin-embedded sections accompanying marked neutrophilic infiltration were the target of analysis. Neutrophil-associated substances (citrullinated histone H3, lactoferrin, myeloperoxidase and neutrophil elastase) were evaluated as NETs markers, while fibrinogen gamma chain was employed as a fibrin marker. Light microscopically, the fibrils were categorized into three types: thin, thick and clustered thick. Lactoferrin represented a good and stable NETs marker. Thin fibrils belonged to NETs. Thick fibrils are composed of either mixed NETs and fibrin or fibrin alone. Clustered thick fibrils were solely composed of fibrin. Neutrophils were entrapped within the fibrilllar meshwork of the thin and thick types. Apoptotic cells immunoreactive to cleaved caspase 3 and cleaved actin were dispersed in the NETs. In conclusion, NETs and fibrin meshwork were consistently recognizable by immunostaining for lactoferrin and fibrinogen gamma chain. PMID- 27682015 TI - Visualization of Neutrophil Extracellular Traps and Fibrin Meshwork in Human Fibrinopurulent Inflammatory Lesions: II. Ultrastructural Study. AB - Neutrophil extracellular traps (NETs) represent an extracellular, spider's web like structure resulting from cell death of neutrophils. NETs play an important role in innate immunity against microbial infection, but their roles in human pathological processes remain largely unknown. NETs and fibrin meshwork both showing fibrillar structures are observed at the site of fibrinopurulent inflammation, as described in our sister paper [Acta Histochem. Cytochem. 49; 109 116, 2016]. In the present study, immunoelectron microscopic study was performed for visualizing NETs and fibrin fibrils (thick fibrils in our tongue) in formalin fixed, paraffin-embedded sections of autopsied lung tissue of legionnaire's pneumonia. Lactoferrin and fibrinogen gamma chain were utilized as markers of NETs and fibrin, respectively. Analysis of immuno-scanning electron microscopy indicated that NETs constructed thin fibrils and granular materials were attached onto the NETs fibrils. The smooth-surfaced fibrin fibrils were much thicker than the NETs fibrils. Pre-embedding immunoelectron microscopy demonstrated that lactoferrin immunoreactivities were visible as dots on the fibrils, whereas fibrinogen gamma chain immunoreactivities were homogeneously observed throughout the fibrils. Usefulness of immunoelectron microscopic analysis of NETs and fibrin fibrils should be emphasized. PMID- 27682016 TI - p62 Regulates the Proliferation of Molecular Apocrine Breast Cancer Cells. AB - p62, also called sequestosome 1 (SQSTM1), is a multifunctional signaling molecule that affects cell proliferation. Recently, we found accumulation of p62 in apocrine carcinoma of the breast, however, the biological role of p62 expression in apocrine carcinoma still remains unclear. To investigate whether p62 might contribute to tumor cell proliferation in apocrine carcinomas, we used the MDA-MB 453 (androgen receptor-positive, HER2-type) and MFM223 (androgen receptor positive, triple-negative type) breast cancer cell lines as models of molecular apocrine carcinoma. Both MDA-MB-453 and MFM223 showed strong and d high p62 protein expression than MCF7 cells (androgen receptor-negative, luminal A type). Knockdown of p62 resulted in significant reduction of the cell proliferative activity in both MDA-MB-453 (P<0.01) and MFM223 (P<0.05). In conclusion, p62 could contribute to cell proliferation and represent a therapeutic target in apocrine carcinoma. PMID- 27682017 TI - Investigating the Effect of Gaze Cues and Emotional Expressions on the Affective Evaluations of Unfamiliar Faces. AB - People look at what they are interested in, and their emotional expressions tend to indicate how they feel about the objects at which they look. The combination of gaze direction and emotional expression can therefore convey important information about people's evaluations of the objects in their environment, and can even influence the subsequent evaluations of those objects by a third party, a phenomenon known as the emotional gaze effect. The present study extended research into the effect of emotional gaze cues by investigating whether they affect evaluations of the most important aspect of our social environment-other people-and whether the presence of multiple gaze cues enhances this effect. Over four experiments, a factorial within-subjects design employing both null hypothesis significance testing and a Bayesian statistical analysis replicated previous work showing an emotional gaze effect for objects, but found strong evidence that emotional gaze cues do not affect evaluations of other people, and that multiple, simultaneously presented gaze cues do not enhance the emotional gaze effect for either the evaluations of objects or of people. Overall, our results suggest that emotional gaze cues have a relatively weak influence on affective evaluations, especially of those aspects of our environment that automatically elicit affectively valenced reactions, including other humans. PMID- 27682019 TI - Heat Generation During Bone Drilling: A Comparison Between Industrial and Orthopaedic Drill Bits. AB - OBJECTIVES: Cortical bone drilling for preparation of screw placement is common in multiple surgical fields. The heat generated while drilling may reach thresholds high enough to cause osteonecrosis. This can compromise implant stability. Orthopaedic drill bits are several orders more expensive than their similarly sized, publicly available industrial counterparts. We hypothesize that an industrial bit will generate less heat during drilling, and the bits will not generate more heat after multiple cortical passes. METHODS: We compared 4 4.0 mm orthopaedic and 1 3.97 mm industrial drill bits. Three types of each bit were drilled into porcine femoral cortices 20 times. The temperature of the bone was measured with thermocouple transducers. The heat generated during the first 5 drill cycles for each bit was compared to the last 5 cycles. These data were analyzed with analysis of covariance. RESULTS: The industrial drill bit generated the smallest mean increase in temperature (2.8 +/- 0.29 degrees C) P < 0.0001. No significant difference was identified comparing the first 5 cortices drilled to the last 5 cortices drilled for each bit. The P-values are as follows: Bosch (P = 0.73), Emerge (P = 0.09), Smith & Nephew (P = 0.08), Stryker (P = 0.086), and Synthes (P = 0.16). The industrial bit generated less heat during drilling than its orthopaedic counterparts. The bits maintained their performance after 20 drill cycles. CONCLUSIONS: Consideration should be given by manufacturers to design differences that may contribute to a more efficient cutting bit. Further investigation into the reuse of these drill bits may be warranted, as our data suggest their efficiency is maintained after multiple uses. PMID- 27682020 TI - Use of Inlet-Obturator Oblique View (Leeds View) for Placement of Posterior Wall Screws in Acetabular Fracture Surgery. AB - Posterior wall (PW) fractures are the most common fractures requiring surgical fixation in acetabular surgery. Extra-articular screw placement must be confirmed intraoperatively. Herein we describe the use of the inlet and obturator oblique view (the Leeds view) for screw placement in elementary PW and in associated both column with PW fractures. We highlight our steps to ensure accurate placement in a small series of patients. PMID- 27682018 TI - Access to Emergency Contraception in the Over-the-Counter Era. AB - INTRODUCTION: After years of complex regulatory changes, levonorgestrel (LNG) emergency contraception (EC) is now approved for unrestricted sale in the United States. Timely access to EC pills is critical because they are more likely to work the sooner they are taken. This study assesses whether LNG EC is sold in accordance with current Food and Drug Administration regulations. METHODS: We distributed an online questionnaire through an EC-focused listserv for reproductive health professionals, asking data collectors to visit local stores and document product names, price, over-the-counter shelf availability, and misinformation about age restrictions. We used chi2 analysis to assess bivariate associations and t tests and Wilcoxon rank-sum tests to determine differences in means. RESULTS: We collected information about 220 stores. The majority (65%) stocked EC on over-the-counter shelves, although only 22% of these displayed it without a locked security enclosure. Chain pharmacies were more likely to shelf stock EC than independent pharmacies (77% vs. 5%; p = .000), but variation existed among stores within the same chain. Among stores that were asked, 40% incorrectly reported an age restriction for non-prescription purchase of LNG EC, whereas 95% correctly reported that men can buy LNG EC. The average price of branded and generic LNG EC was $49.64 and $40.05, respectively. CONCLUSIONS: Changes in the regulatory status of LNG EC have resulted in widespread confusion about how EC can be sold, and its high price contributes to access barriers. Retailers should ensure that consumers can access LNG EC quickly and easily by stocking the product on over-the-counter shelves and educating staff about current regulations. PMID- 27682021 TI - A Comparison of Sound Levels in Open Plan Versus Pods in a Neonatal Intensive Care Unit. AB - OBJECTIVE: The objective of this study was to compare the noise levels recorded in two different neonatal intensive care unit (NICU) settings: a pod and an open plan NICU located in the same hospital. BACKGROUND: The NICU is a busy environment with ambient noise levels that often exceed established recommendations. This noise deleteriously affects the physiological stability and developmental outcomes of sick and preterm infants. Pods have reduced numbers of cots (in this case, 6) compared to open plan NICUs (in this case, 11), yet the noise levels in pods have not been reported. METHOD: This study compared real time decibel (dB) levels in an A-weighted scale, captured continuously by sound dosimeters mounted in both NICU settings for a period of 4 weeks: a pod setting and an open plan NICU. Researchers also collected observational data. RESULTS: The average noise level recorded in the pod was 3 dBs less than in the open plan NICU. This result was statistically significant. However, dB recordings in both areas were over the recommended limits by 4-6 dBs, with isolated peaks between 74.5 dBs (NICU) and 75.9 dBs (pod). Observational data confirmed this correlation. CONCLUSIONS: Further research to evaluate interventions to decrease the noise levels in both settings are needed, especially during times of peak activity. Staff working in these settings need to be more aware that control of acoustic levels is important in the neuroprotection of neonates. Coupling this with careful consideration to structural components and evidence-based design planning may contribute to lowering dB levels in the NICU environment. PMID- 27682022 TI - Delivering risk information in a dynamic information environment: Framing and authoritative voice in Centers for Disease Control (CDC) and primetime broadcast news media communications during the 2014 Ebola outbreak. AB - OBJECTIVE: During a disease outbreak, media serve as primary transmitters of information from public health agencies to the public, and have been shown to influence both behavior and perception of risk. Differences in news frequency, framing and information source can impact the public's interpretation of risk messages and subsequent attitudes and behaviors about a particular threat. The media's framing of an outbreak is important, as it may affect both perception of risk and the ability to process important health information. METHODS: To understand how risk communication by the Centers for Disease Control and Prevention (CDC) during the 2014 Ebola outbreak was framed and delivered and to what extent primetime broadcast news media mirrored CDC's framing and authoritative voice, 209 CDC communications and primetime broadcast transcripts issued between July 24 and December 29, 2014 were analyzed and coded by thematic frame and authoritative voice. Dominant frame and voice were determined for each month and for overall period of analysis. RESULTS: Medical frame was dominant in CDC (60%), Anderson Cooper 360 (49%), The Rachel Maddow Show (47%) and All In with Chris Hayes (47%). The human interest frame was dominant in The Kelly File (45%), while The O'Reilly Factor coverage was equally split between sociopolitical and medical frames (28%, respectively). Primetime news media also changed dominant frames over time. Dominant authoritative voice in CDC communications was that of CDC officials, while primetime news dominantly featured local and federal (non-CDC) government officials and academic/medical experts. CONCLUSION: Differences in framing and delivery could have led the public to interpret risk in a different way than intended by CDC. Overall, public health agencies should consider adapting risk communication strategies to account for a dynamic news environment and the media's agenda. Options include adapting communications to short-form styles and embracing the concept of storytelling. PMID- 27682023 TI - Fear, vulnerability and sacrifice: Drivers of emergency department use and implications for policy. AB - Patients' existential fears of unknowns associated with illness and unusual bodily signs and symptoms are common, but unexamined drivers to the emergency department (ED). This paper examines a May 2015 case study of a 51-year-old low income, recently insured, African American man in Philadelphia (USA) who had two recent ED visits for evaluation of frequent headaches and described fear of being at risk for a stroke. Through ethnographic methods and anthropological analyses we find that fear of failing to fulfill social roles due to a potentially debilitating illness, and fear of burdening family members with medical bills resulting from doctor's visits affect this man's patterns of health-seeking behaviors. While current popular and policy discourses emphasize crowded EDs and ED "overuse," our analysis locates health-seeking behavior within a context of this man's social and medical history. We layer the impact of macrosocial forces with an analysis of his subjectivity to develop a robust understanding of how his patterns of seeking care reflect agency. In so doing, we reveal how this approach can inform policy interventions that could create entry points for patients to access the primary care they need in settings that are best suited to their condition, and leads researchers away from the unproductive binary of "appropriate" and "inappropriate" users that blames patients for seeking acute care. We suggest that institutions develop structural competency to address administrative "inattentional blindness" that erects barriers to care. Specifically, we recommend: increasing insurance coverage among individuals and across populations, and enacting place-based community-level care by employing community health workers. PMID- 27682024 TI - Bioinformatics analysis of gene expression profile data to screen key genes involved in pulmonary sarcoidosis. AB - BACKGROUND: Sarcoidosis is a multisystemic inflammatory and granulomatous disease that occurs in almost all populations and affects multiple organs. Meanwhile, its most common manifestation is pulmonary sarcoidosis. This study aimed to identify effective biomarkers for the diagnosis and therapy of pulmonary sarcoidosis. METHODS: GSE16538 was downloaded from Gene Expression Omnibus, including 6 pulmonary sarcoidosis samples and 6 normal lung samples. Then, differentially expressed genes (DEGs) were identified by limma package in R. After the expression values of the DEGs were extracted, hierarchical clustering analysis was performed for the DEGs using the pheatmap package in R. Subsequently, protein protein interaction (PPI) pairs among the DEGs were searched by STRING or REACTOME databases, and then PPI networks were visualized by Cytoscape software. Using DAVID and KOBAS, functional and pathway enrichment analyses separately were performed for the DEGs involved in the PPI network. RESULTS: Total 208 DEGs were identified in pulmonary sarcoidosis samples, including 179 up-regulated genes and 29 down-regulated genes. Hierarchical clustering showed that the DEGs could clearly distinguish the pulmonary sarcoidosis samples from the normal lung samples. In the PPI network constructed by STRING database, CXCL9, STAT1, CCL5, CXCL11 and GBP1 had higher degrees and betweenness values, and could interact with each other. Functional enrichment showed that CXCL9, CXCL11 and CCL5 were enriched in immune response. Moreover, STAT1 was enriched in pathways of chemokine signaling pathway and JAK-STAT signaling pathway. CONCLUSION: CXCL9, CXCL11, STAT1, CCL5 and GBP1 might be implicated in pulmonary sarcoidosis through interacting with each other. PMID- 27682025 TI - Short-Term Memory Performance in 7- and 8-Year-Old Children: The Relationship Between Phonological and Pitch Processing. AB - Purpose: The relationship between short-term memory for phonology and pitch was explored by examining accuracy scores for typically developing children for 5 experimental tasks: immediate nonword repetition (NWR), nonword repetition with an 8-s silent interference (NWRS), pitch discrimination (PD), pitch discrimination with an 8-s silent interference (PDS), and pitch matching (PM). Method: Thirty-six 7- and 8-year-old children (21 girls, 15 boys) with normal hearing, language, and cognition were asked to listen to and repeat nonsense words (NWR, NWRS), make a same versus different decision between 2 tones (PD, PDS), and listen to and then vocally reproduce a tone (PM). Results: Results showed no significant correlations between tasks of phonological memory and tests of pitch memory, that participants scored significantly better on nonword repetition tasks than PD and PM tasks, and that participants performed significantly better on tasks with no silent interference. Discussion: These findings suggest that, for typically developing children, pitch may be stored and rehearsed in a separate location than phonological information. Because of fundamental task differences, further research is needed to corroborate these data and determine the presence of developmental effects and neuroanatomical locations where a potential language/music overlap is occurring in children. PMID- 27682026 TI - Mathematical model of the post-ablation enhancement zone as a tissue-level oedematic response. AB - PURPOSE: A hyperdense rim is commonly observed at the periphery of ablation zones during post-ablation imaging (e.g. ultrasound) in tumours. A mathematical model has been developed here to investigate the occurrence of this enhanced rim, caused by the ablated cells, giving an indication of the location of the final ablation region. MATERIALS AND METHODS: The enhanced rim has been assumed here to be due to a tissue-level oedematic response of viable cells, which necessitated coupling multiple modelling elements in a spatially distributed system: thermal cell death, tissue-state dependent ion concentration dynamics, ion transport in the extracellular space, and osmotic cell volume regulation. RESULTS: In response to the imposed temperature function, an ablation zone was predicted, distinguishing the tissue state between 'dead' and 'alive'. A disturbance in intracellular/extracellular ion concentrations was induced due to ion redistribution, which acted as an osmotic stress and contributed to significant cell swelling in a thin rim at the periphery of the ablation zone. It was also found that the rim size only changed slightly with varying lesion size, in response to different temperature profiles. CONCLUSIONS: The study presents a novel mathematical model to understand the enhanced rim surrounding the ablation zone by assuming tissue-level cell oedema as the primary potential cause. The model links the direct response to thermal injury to an observable secondary response, which could be of clinical value in that the location of this bright ring could potentially be used for more accurate determination of the extent of the ablation zone. PMID- 27682027 TI - Prognostic significance of platelet count changes during hospitalization for community-acquired pneumonia. AB - The prognostic significance of platelet count (PC) changes during hospitalization for community-acquired pneumonia (CAP) has not been investigated. For 976 adults, clinical data during hospitalization for CAP and all-cause mortality following discharge were compared according to DeltaPC (PC on discharge minus PC on admission): groups A (declining PC, DeltaPC < -50 * 109/l), B (stable PC, DeltaPC +/- 50 * 109/l), and C (rising PC, DeltaPC >50 * 109/l), and according to the presence of thrombocytopenia, normal PC, and thrombocytosis on admission/discharge. Groups A, B, and C comprised 7.9%, 46.5%, and 45.6% of patients, respectively. On hospital admission/discharge, thrombocytopenia, normal PC, and thrombocytosis were observed in 12.8%/6.4%, 84.1%/84.4%, and 3.1%/9.2% of patients, respectively. The respective 90-day, 3-year, and total (median follow up of 54 months) mortality rates were significantly higher: in group A (40.3%, 63.6%, and 72.7%), compared to groups B (12.3%, 31.5%, and 39.0%) and C (4.9%, 17.3%, and 25.4%), p < 0.001; and in patients with thrombocytopenia at discharge (27.4%, 48.4%, and 51.6%), compared to those with normal PC (10.2%, 26.9%, and 35.4%) and thrombocytosis (8.9%, 17.8%, and 24.4%) at discharge (p < 0.001). Mortality rates were comparable among groups with thrombocytopenia, normal PC, and thrombocytosis at admission (p = 0.6). In the entire sample, each 100 * 109/l increment of DeltaPC strongly predicted lower mortality (p < 0.001, relative risk 0.73, 95% confidence interval 0.64-0.83). In conclusion, PC changes are common among CAP inpatients. Rising PC throughout hospitalization is a powerful predictor of better survival, while declining PC predicts poor outcome. Evaluation of PC changes during hospitalization for CAP may provide useful prognostic information. PMID- 27682028 TI - Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells. AB - Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol's effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event associated with alcohol-related peripheral neuropathy of an enhanced nociceptive response. PMID- 27682030 TI - Clinical Anatomy of the Cavotricuspid Isthmus and Terminal Crest. AB - The aim of this study was to provide useful information about the cavotricuspid isthmus (CTI) and surrounding areas morphology, which may help to plan CTI radio frequency ablation. We examined 140 autopsied human hearts from Caucasian individuals of both sexes (29.3% females) with a mean age of 49.1+/-17.2 years. We macroscopically investigated the lower part of the right atrium, the CTI, the inferior vena cava ostium and the terminal crest. The paraseptal isthmus (18.5+/ 4.0 mm) was significantly shorter than the central isthmus (p<0.0001), and the central isthmus (24.0+/-4.2 mm) was significantly shorter than the inferolateral isthmus (29.3+/-4.9 mm) (p<0.0001). Heart weight was positively correlated with all isthmus diameters. Three different sectors of CTI were distinguished: anterior, middle and posterior. The middle sector of the CTI presented a different morphology: trabeculae (N = 87; 62.1%), intertrabecular recesses (N = 35; 25.0%) and trabecular bridges (N = 18; 12.9%). A single sub-Eustachian recess was present in 48.6% of hearts (N = 68), and a double recess was present in 2.9% of hearts (N = 4) with mean depth = 5.6+/-1.8mm and diameter = 7.1+/-3.4mm. The morphology of the distal terminal crest was varied; 10 patterns of the distal terminal crest ramifications were noted. There were no statistically significant differences in any of the investigated CTI parameters between groups with different types of terminal crest ramifications. The presence of intertrabecular recesses (25.0%), trabecular bridges (12.9%) and sub-Eustachian recesses (48.6%) within the CTI can make ablation more difficult. We have presented the macroscopic patterns of final ramifications of the terminal crest within the quadrilateral CTI area. PMID- 27682029 TI - Investigating Teamwork in the Operating Room: Engaging Stakeholders and Setting the Agenda. PMID- 27682031 TI - Considerations for Developing a Zika Virus Vaccine. PMID- 27682032 TI - Fast-Track Zika Vaccine Development - Is It Possible? PMID- 27682033 TI - Predicting the Future - Big Data, Machine Learning, and Clinical Medicine. PMID- 27682035 TI - CLINICAL PRACTICE. Influenza Vaccination. PMID- 27682036 TI - IMAGES IN CLINICAL MEDICINE. Human Papillomavirus-Associated Oropharyngeal Squamous-Cell Carcinoma. PMID- 27682037 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 30-2016. A 63-Year-Old Woman with Bipolar Disorder, Cancer, and Worsening Depression. PMID- 27682034 TI - Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. AB - BACKGROUND: The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended spectrum prophylaxis in women undergoing nonelective cesarean section. METHODS: In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. RESULTS: The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63). CONCLUSIONS: Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .). PMID- 27682038 TI - Antibiotic Prophylaxis for Cesarean Delivery - When Broader Is Better. PMID- 27682039 TI - Limits to Personalized Cancer Medicine. PMID- 27682040 TI - Mitochondrial Mobility and Neuronal Recovery. PMID- 27682041 TI - Preventing Catheter-Associated Urinary Tract Infections. PMID- 27682042 TI - Preventing Catheter-Associated Urinary Tract Infections. PMID- 27682043 TI - Preventing Catheter-Associated Urinary Tract Infections. PMID- 27682044 TI - Preventing Catheter-Associated Urinary Tract Infections. PMID- 27682045 TI - Body-Mass Index in Adolescence and Cardiovascular Death in Adulthood. PMID- 27682046 TI - Body-Mass Index in Adolescence and Cardiovascular Death in Adulthood. PMID- 27682047 TI - Body-Mass Index in Adolescence and Cardiovascular Death in Adulthood. PMID- 27682048 TI - Sudden Cardiac Death in Children and Young Adults. PMID- 27682049 TI - Sudden Cardiac Death in Children and Young Adults. PMID- 27682050 TI - Ankylosing Spondylitis and Axial Spondyloarthritis. PMID- 27682051 TI - Ankylosing Spondylitis and Axial Spondyloarthritis. PMID- 27682052 TI - Ankylosing Spondylitis and Axial Spondyloarthritis. PMID- 27682054 TI - Stellar Quake. PMID- 27682053 TI - Viral Load Kinetics of MERS Coronavirus Infection. PMID- 27682055 TI - IMAGES IN CLINICAL MEDICINE. Lymphangitis on the Abdomen. PMID- 27682056 TI - Crystallopathies. PMID- 27682057 TI - Crystallopathies. PMID- 27682058 TI - Crystallopathies. PMID- 27682059 TI - New Lignans from Antidesma hainanensis Inhibit NO Production in BV2 Microglial Cells. AB - Two new lignans (7S,7'R,8S,8'R)-3,3'-dimethoxy-7,7'-epoxylignan-4,4',9-triol 4-O beta-D-glucopyranoside (1) and 9-O-formylaviculin (2) together with other thirteen known secondary metabolites were isolated from the leaves of Antidesma hainanensis. Their chemical structures were determined using NMR, electrospray ionization (ESI)-MS, circular dichroism (CD) spectroscopic methods, and as well as by comparison with those reported in the literature. Neuro-inflammatory activity of isolated compounds was evaluated by their inhibition on nitric oxide (NO) production in activated BV2 microglial cells. At concentration of 40 uM, compounds 1-3, 5, 7, 8, 9, 14, and 15 exhibited inhibitory effects over 50%, suggesting that they could be potential candidate drugs for the cure of neuro inflammation. In addition, compounds 1, 8, 14, and 15 significantly inhibited 16.23, 27.76, 21.23, and 29.44% NO production at diluted concentration as low as 2.5 uM. PMID- 27682060 TI - Brokering Community Engagement: Proactive Strategies for Supporting Indigenous Australians with Mental Health Problems. AB - This qualitative study explored the experiences of mental health employees working with Indigenous clients living with mental illness. Interviews were conducted with 20 mental health workers to identify strategies they adopt to facilitate community engagement with Indigenous clients. Using a thematic analysis approach, 'Brokering community engagement' was the umbrella theme from which two subthemes related to community engagement for the service and clients emerged (1) enabling connections -community and family; and (2) recovery and reconnecting with community. Participant insights enabled a deeper understanding of the role of community in the recovery process for Indigenous clients and highlight the importance of community engagement as a primary, yet multifaceted strategy used by mental health workers in the communities they serve. PMID- 27682062 TI - Drug resistant integrase mutants cause aberrant HIV integrations. AB - BACKGROUND: HIV-1 integrase is the target for three FDA-approved drugs, raltegravir, elvitegravir, and dolutegravir. All three drugs bind at the active site of integrase and block the strand transfer step of integration. We previously showed that sub-optimal doses of the anti-HIV drug raltegravir can cause aberrant HIV integrations that are accompanied by a variety of deletions, duplications, insertions and inversions of the adjacent host sequences. RESULTS: We show here that a second drug, elvitegravir, also causes similar aberrant integrations. More importantly, we show that at least two of the three clinically relevant drug resistant integrase mutants we tested, N155H and G140S/Q148H, which reduce the enzymatic activity of integrase, can cause the same sorts of aberrant integrations, even in the absence of drugs. In addition, these drug resistant mutants have an elevated IC50 for anti-integrase drugs, and concentrations of the drugs that would be optimal against the WT virus are suboptimal for the mutants. CONCLUSIONS: We previously showed that suboptimal doses of a drug that binds to the HIV enzyme integrase and blocks the integration of a DNA copy of the viral genome into host DNA can cause aberrant integrations that involve rearrangements of the host DNA. We show here that suboptimal doses of a second anti-integrase drug can cause similar aberrant integrations. We also show that drug-resistance mutations in HIV integrase can also cause aberrant integrations, even in the absence of an anti-integrase drug. HIV DNA integrations in the oncogenes BACH2 and MKL2 that do not involve rearrangements of the viral or host DNA can stimulate the proliferation of infected cells. Based on what is known about the association of DNA rearrangements and the activation of oncogenes in human tumors, it is possible that some of the deletions, duplications, insertions, and inversions of the host DNA that accompany aberrant HIV DNA integrations could increase the chances that HIV integrations could lead to the development of a tumor. PMID- 27682063 TI - The Molecular Epidemiology and Antimicrobial Resistance of Neisseria gonorrhoeae in Australia: A Nationwide Cross-Sectional Study, 2012. AB - BACKGROUND: Antimicrobial resistance (AMR) by Neisseria gonorrhoeae is considered a serious global threat. METHODS: In this nationwide study, we used MassARRAY iPLEX genotyping technology to examine the epidemiology of N. gonorrhoeae and associated AMR in the Australian population. All available N. gonorrhoeae isolates (n = 2452) received from Australian reference laboratories from January to June 2012 were included in the study. Genotypic data were combined with phenotypic AMR information to define strain types. RESULTS: A total of 270 distinct strain types were observed. The 40 most common strain types accounted for over 80% of isolates, and the 10 most common strain types accounted for almost half of all isolates. The high male to female ratios (>94% male) suggested that at least 22 of the top 40 strain types were primarily circulating within networks of men who have sex with men (MSM). Particular strain types were also concentrated among females: two strain types accounted for 37.5% of all isolates from females. Isolates harbouring the mosaic penicillin binding protein 2 (PBP2)-considered a key mechanism for cephalosporin resistance-comprised 8.9% of all N. gonorrhoeae isolates and were primarily observed in males (95%). CONCLUSIONS: This large scale epidemiological investigation demonstrated that N. gonorrhoeae infections are dominated by relatively few strain types. The commonest strain types were concentrated in MSM in urban areas and Indigenous heterosexuals in remote areas, and we were able to confirm a resurgent epidemic in heterosexual networks in urban areas. The prevalence of mosaic PBP2 harboring N. gonorrhoeae strains highlight the ability for new N. gonorrhoeae strains to spread and become established across populations. PMID- 27682064 TI - Home Environment as a Source of Life-Threatening Azole-Resistant Aspergillus fumigatus in Immunocompromised Patients. AB - A case of fatal aspergillosis due to a TR46/Y121F/T289A azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR46/Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis. PMID- 27682065 TI - Zika Virus Genital Tract Shedding in Infected Women of Childbearing age. PMID- 27682066 TI - Reply to Sullivan. PMID- 27682068 TI - A Randomized Study Evaluating Oral Fusidic Acid (CEM-102) in Combination With Oral Rifampin Compared With Standard-of-Care Antibiotics for Treatment of Prosthetic Joint Infections: A Newly Identified Drug-Drug Interaction. AB - BACKGROUND: Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described. METHODS: In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively. RESULTS: Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected. CONCLUSIONS: The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research. CLINICAL TRIALS REGISTRATION: NCT01756924. PMID- 27682069 TI - Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. AB - Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2002. Since then, there have been major developments in its diagnosis and management. Therefore, the CMV Drug Development Forum consisting of scientists, clinicians, regulators, and industry representatives has produced an updated version incorporating recent knowledge with the aim to support clinical research and drug development. The main changes compared to previous definitions are the introduction of a "probable disease" category and to incorporate quantitative nucleic acid testing in some end-organ disease categories. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts between scientists, regulators, and industry can provide a platform for this work. PMID- 27682067 TI - Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct Acting Antivirals Don't Change a Thing. AB - Currently, 380 000-400 000 occupational exposures to blood-borne pathogens occur annually in the United States. The management for occupational HIV or hepatitis B virus exposures includes postexposure prophylaxis (PEP) when necessary; however, PEP is not recommended for hepatitis C virus (HCV) exposures. Recent approval of HCV direct-acting antivirals (DAAs) has renewed discussions as to whether these therapies could be used to prevent infection after exposure. There are no published studies addressing this question, but the prescribing of DAAs for PEP has been reported. We will discuss the differences in transmission of the 3 most common blood-borne pathogens, the natural history of early HCV infection, and the scientific rationale for PEP. In particular, we will discuss how the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use. PMID- 27682070 TI - Measuring Appropriate Antimicrobial Use: Attempts at Opening the Black Box. AB - Indiscriminate antimicrobial use has plagued medicine since antibiotics were first introduced into clinical practice >70 years ago. Infectious diseases physicians and public health officials have advocated for preservation of these life-saving drugs for many years. With rising burden of antimicrobial-resistant organisms and Clostridium difficile infections, halting unnecessary antimicrobial use has become one of the largest public health concerns of our time. Inappropriate antimicrobial use has been quantified in various settings using numerous definitions; however, no established reference standard exists. With mounting national efforts to improve antimicrobial use, a consensus definition and standard method of measuring appropriate antimicrobial use is imperative. We review existing literature on systematic approaches to define and measure appropriate antimicrobial use, and describe a collaborative effort at developing standardized audit tools for assessing the quality of antimicrobial prescribing. PMID- 27682071 TI - Declining Interest in Infectious Diseases: An Economic Problem That Requires Economic Solutions. PMID- 27682072 TI - How anorexia nervosa patients with high and low autistic traits respond to group Cognitive Remediation Therapy. AB - BACKGROUND: The current study aimed to evaluate group Cognitive remediation therapy (CRT) inpatients with Anorexia Nervosa (AN). We aimed to examine the treatment response of group CRT in AN patients with high or low levels of autistic traits. METHODS: Thirty-five in patients with an AN diagnosis received group CRT intervention for 6 sessions in a national eating disorder unit. All participants completed self-report questionnaires on thinking styles and motivation before and after the intervention. RESULTS: Patients with low autistic traits had statistically significant medium size effect improvements in self reported thinking style scales as well as confidence (ability) to change. Patients with high autistic traits showed no statistically significant improvements in any outcome measure. CONCLUSIONS: The brief group format CRT intervention improves self-reported cognitive and motivational aspects in people with AN without autistic traits. For patients with higher autistic traits brief group CRT does not improve self-reported cognitive style or motivation. This finding suggests that brief group format CRT might not be the best suited format for individuals with elevated autistic traits and individual or more tailored CRT should be explored. PMID- 27682073 TI - Priorities in the Polish health care system. AB - Since 1999, Polish health policy has changed, the quality of services has increased, and also the level of financing, mainly from public benefits. Despite constant growth of indexes reflecting the health status of Polish society, such as life expectancy, quality of life, or decreasing index of deaths at birth, just as in the majority of European countries, in Poland the society is growing older, which implies the necessity to reorganize the system. In this paper, the author has described the most important factors that determine the operation of the health system in Poland, as well as presents the ways it was restructured over the last few years, taking into consideration the structural, legislative, financial, organizational, and quantitative aspects. Also, the latest trends in Polish health policy, which take into account new goals of the system, have been presented within. PMID- 27682075 TI - Identification of Multiple Bacteriocins in Enterococcus spp. Using an Enterococcus-Specific Bacteriocin PCR Array. AB - Twenty-two bacteriocin-producing Enterococcus isolates obtained from food and animal sources, and demonstrating activity against Listeria monocytogenes, were screened for bacteriocin-related genes using a bacteriocin PCR array based on known enterococcal bacteriocin gene sequences in the NCBI GenBank database. The 22 bacteriocin-positive (Bac+) enterococci included En. durans (1), En. faecalis (4), En. faecium (12), En. hirae (3), and En. thailandicus (2). Enterocin A (entA), enterocins mr10A and mr10B (mr10AB), and bacteriocin T8 (bacA) were the most commonly found structural genes in order of decreasing prevalence. Forty five bacteriocin genes were identified within the 22 Bac+ isolates, each containing at least one of the screened structural genes. Of the 22 Bac+ isolates, 15 possessed two bacteriocin genes, seven isolates contained three different bacteriocins, and three isolates contained as many as four different bacteriocin genes. These results may explain the high degree of bactericidal activity observed with various Bac+ Enterococcus spp. Antimicrobial activity against wild-type L. monocytogenes and a bacteriocin-resistant variant demonstrated bacteriocins having different modes-of-action. Mixtures of bacteriocins, especially those with different modes-of-action and having activity against foodborne pathogens, such as L. monocytogenes, may play a promising role in the preservation of food. PMID- 27682074 TI - Diagnostic and Prognostic Value of MicroRNA in Viral Diseases. AB - Virology is probably the most rapidly developing field within clinical laboratory medicine. Adequate diagnostic methods exist for the diagnostics of most acute viral infections. However, emergence of pathogenic viruses or virus strains and new disease associations of known viruses require the establishment of new diagnostic methods, sometimes very rapidly. In the field of chronic or persistent viral diseases, particularly those involving potential of malignant or fatal development, there is a constant need for improved differential diagnostics, monitoring, prognosis and risk assessment. Increasing understanding of disease pathogenesis also enables better patient management and personalized medicine, where companion diagnostics can offer precise and specific tools for individual care. Very often the new tools are offered by molecular diagnostic techniques, and this includes the detection of microRNAs (miRNAs). miRNAs are small regulatory RNA molecules, which regulate the expression of their target genes. They are encoded both by viruses and their host, and both can target either viral or cellular gene expression. In this review the diagnostic possibilities offered by miRNA will be discussed. The focus will be on selected viral and human miRNAs in viral diseases, and examples of miRNAs of putative diagnostic potential will be presented. PMID- 27682076 TI - Rapid Reactivation of Deep Subsurface Microbes in the Presence of C-1 Compounds. AB - Microorganisms in the deep biosphere are believed to conduct little metabolic activity due to low nutrient availability in these environments. However, destructive penetration to long-isolated bedrock environments during construction of underground waste repositories can lead to increased nutrient availability and potentially affect the long-term stability of the repository systems, Here, we studied how microorganisms present in fracture fluid from a depth of 500 m in Outokumpu, Finland, respond to simple carbon compounds (C-1 compounds) in the presence or absence of sulphate as an electron acceptor. C-1 compounds such as methane and methanol are important intermediates in the deep subsurface carbon cycle, and electron acceptors such as sulphate are critical components of oxidation processes. Fracture fluid samples were incubated in vitro with either methane or methanol in the presence or absence of sulphate as an electron acceptor. Metabolic response was measured by staining the microbial cells with fluorescent dyes that indicate metabolic activity and transcriptional response with RT-qPCR. Our results show that deep subsurface microbes exist in dormant states but rapidly reactivate their transcription and respiration systems in the presence of C-1 substrates, particularly methane. Microbial activity was further enhanced by the addition of sulphate as an electron acceptor. Sulphate- and nitrate-reducing microbes were particularly responsive to the addition of C-1 compounds and sulphate. These taxa are common in deep biosphere environments and may be affected by conditions disturbed by bedrock intrusion, as from drilling and excavation for long-term storage of hazardous waste. PMID- 27682077 TI - Fumaric Acid and Slightly Acidic Electrolyzed Water Inactivate Gram Positive and Gram Negative Foodborne Pathogens. AB - Sanitizing effectiveness of slightly acidic electrolyzed water (SAEW) and fumaric acid (FA) at different dipping temperatures (25-60 degrees C), times (1-5 min), and concentrations (5-30 ppm for SAEW and 0.125%-0.5% for FA) on pure cultures of two Gram positive pathogens Staphylococcus aureus (SA) and Listeria monocytogenes (LM) and two Gram negative pathogens Escherichia coli O157:H7 (EC) and Salmonella Typhimurium (ST) was evaluated. FA (0.25%) showed the strongest sanitizing effect, demonstrating complete inactivation of EC, ST, and LM, while SA was reduced by 3.95-5.76 log CFU/mL at 25-60 degrees C, respectively, after 1 min of treatment. For SAEW, the complete inactivation was obtained when available chlorine concentration was increased to 20 ppm at 40 degrees C for 3 and 5 min. Moreover, Gram positive pathogens have been shown to resist to all treatment trends more than Gram negative pathogens throughout this experiment. Regardless of the different dipping temperatures, concentrations, and times, FA treatment was more effective than treatment with SAEW for reduction of foodborne pathogens. This study demonstrated that application of FA in food systems may be useful as a method for inactivation of foodborne pathogens. PMID- 27682078 TI - Role of NAD+-Dependent Malate Dehydrogenase in the Metabolism of Methylomicrobium alcaliphilum 20Z and Methylosinus trichosporium OB3b. AB - We have expressed the l-malate dehydrogenase (MDH) genes from aerobic methanotrophs Methylomicrobium alcaliphilum 20Z and Methylosinus trichosporium OB3b as his-tagged proteins in Escherichia coli. The substrate specificities, enzymatic kinetics and oligomeric states of the MDHs have been characterized. Both MDHs were NAD+-specific and thermostable enzymes not affected by metal ions or various organic metabolites. The MDH from M. alcaliphilum 20Z was a homodimeric (2 * 35 kDa) enzyme displaying nearly equal reductive (malate formation) and oxidative (oxaloacetate formation) activities and higher affinity to malate (Km = 0.11 mM) than to oxaloacetate (Km = 0.34 mM). The MDH from M. trichosporium OB3b was homotetrameric (4 * 35 kDa), two-fold more active in the reaction of oxaloacetate reduction compared to malate oxidation and exhibiting higher affinity to oxaloacetate (Km = 0.059 mM) than to malate (Km = 1.28 mM). The kcat/Km ratios indicated that the enzyme from M. alcaliphilum 20Z had a remarkably high catalytic efficiency for malate oxidation, while the MDH of M. trichosporium OB3b was preferable for oxaloacetate reduction. The metabolic roles of the enzymes in the specific metabolism of the two methanotrophs are discussed. PMID- 27682079 TI - Experimental Horizontal Gene Transfer of Methylamine Dehydrogenase Mimics Prevalent Exchange in Nature and Overcomes the Methylamine Growth Constraints Posed by the Sub-Optimal N-Methylglutamate Pathway. AB - Methylamine plays an important role in the global carbon and nitrogen budget; microorganisms that grow on reduced single carbon compounds, methylotrophs, serve as a major biological sink for methylamine in aerobic environments. Two non orthologous, functionally degenerate routes for methylamine oxidation have been studied in methylotrophic Proteobacteria: Methylamine dehydrogenase and the N methylglutamate pathway. Recent work suggests the N-methylglutamate (NMG) pathway may be more common in nature than the well-studied methylamine dehydrogenase (MaDH, encoded by the mau gene cluster). However, the distribution of these pathways across methylotrophs has never been analyzed. Furthermore, even though horizontal gene transfer (HGT) is commonly invoked as a means to transfer these pathways between strains, the physiological barriers to doing so have not been investigated. We found that the NMG pathway is both more abundant and more universally distributed across methylotrophic Proteobacteria compared to MaDH, which displays a patchy distribution and has clearly been transmitted by HGT even amongst very closely related strains. This trend was especially prominent in well characterized strains of the Methylobacterium extroquens species, which also display significant phenotypic variability during methylamine growth. Strains like Methylobacterium extorquens PA1 that only encode the NMG pathway grew on methylamine at least five-fold slower than strains like Methylobacterium extorquens AM1 that also possess the mau gene cluster. By mimicking a HGT event through the introduction of the M. extorquens AM1 mau gene cluster into the PA1 genome, the resulting strain instantaneously achieved a 4.5-fold increase in growth rate on methylamine and a 11-fold increase in fitness on methylamine, which even surpassed the fitness of M. extorquens AM1. In contrast, when three replicate populations of wild type M. extorquens PA1 were evolved on methylamine as the sole carbon and energy source for 150 generations neither fitness nor growth rate improved. These results suggest that the NMG pathway permits slow growth on methylamine and is widely distributed in methylotrophs; however, rapid growth on methylamine can be achieved quite readily through acquisition of the mau cluster by HGT. PMID- 27682080 TI - Isolation and Taxonomic Identity of Bacteriocin-Producing Lactic Acid Bacteria from Retail Foods and Animal Sources. AB - Bacteriocin-producing (Bac+) lactic acid bacteria (LAB) were isolated from a variety of food products and animal sources. Samples were enriched in de Man, Rogosa, and Sharpe (MRS) Lactocilli broth and plated onto MRS agar plates using a "sandwich overlay" technique. Inhibitory activity was detected by the "deferred antagonism" indicator overlay method using Listeria monocytogenes as the primary indicator organism. Antimicrobial activity against L. monocytogenes was detected by 41 isolates obtained from 23 of 170 food samples (14%) and 11 of 110 samples from animal sources (10%) tested. Isolated Bac+ LAB included Lactococcus lactis, Lactobacillus curvatus, Carnobacterium maltaromaticum, Leuconostoc mesenteroides, and Pediococcus acidilactici, as well as Enterococcus faecium, Enterococcus faecalis, Enterococcus hirae, and Enterococcus thailandicus. In addition to these, two Gram-negative bacteria were isolated (Serratia plymuthica, and Serratia ficaria) that demonstrated inhibitory activity against L. monocytogenes, Staphylococcus aureus, and Enterococcus faecalis (S. ficaria additionally showed activity against Salmonella Typhimurium). These data continue to demonstrate that despite more than a decade of antimicrobial interventions on meats and produce, a wide variety of food products still contain Bac+ microbiota that are likely eaten by consumers and may have application as natural food preservatives. PMID- 27682081 TI - Genomics of Methylotrophy in Gram-Positive Methylamine-Utilizing Bacteria. AB - Gram-positive methylotrophic bacteria have been known for a long period of time, some serving as model organisms for characterizing the specific details of methylotrophy pathways/enzymes within this group. However, genome-based knowledge of methylotrophy within this group has been so far limited to a single species, Bacillus methanolicus (Firmicutes). The paucity of whole-genome data for Gram positive methylotrophs limits our global understanding of methylotrophy within this group, including their roles in specific biogeochemical cycles, as well as their biotechnological potential. Here, we describe the isolation of seven novel strains of Gram-positive methylotrophs that include two strains of Bacillus and five representatives of Actinobacteria classified within two genera, Arthrobacter and Mycobacterium. We report whole-genome sequences for these isolates and present comparative analysis of the methylotrophy functional modules within these genomes. The genomic sequences of these seven novel organisms, all capable of growth on methylated amines, present an important reference dataset for understanding the genomic basis of methylotrophy in Gram-positive methylotrophic bacteria. This study is a major contribution to the field of methylotrophy, aimed at closing the gap in the genomic knowledge of methylotrophy within this diverse group of bacteria. PMID- 27682082 TI - High Throughput Sequencing to Detect Differences in Methanotrophic Methylococcaceae and Methylocystaceae in Surface Peat, Forest Soil, and Sphagnum Moss in Cranesville Swamp Preserve, West Virginia, USA. AB - Northern temperate forest soils and Sphagnum-dominated peatlands are a major source and sink of methane. In these ecosystems, methane is mainly oxidized by aerobic methanotrophic bacteria, which are typically found in aerated forest soils, surface peat, and Sphagnum moss. We contrasted methanotrophic bacterial diversity and abundances from the (i) organic horizon of forest soil; (ii) surface peat; and (iii) submerged Sphagnum moss from Cranesville Swamp Preserve, West Virginia, using multiplex sequencing of bacterial 16S rRNA (V3 region) gene amplicons. From ~1 million reads, >50,000 unique OTUs (Operational Taxonomic Units), 29 and 34 unique sequences were detected in the Methylococcaceae and Methylocystaceae, respectively, and 24 potential methanotrophs in the Beijerinckiaceae were also identified. Methylacidiphilum-like methanotrophs were not detected. Proteobacterial methanotrophic bacteria constitute <2% of microbiota in these environments, with the Methylocystaceae one to two orders of magnitude more abundant than the Methylococcaceae in all environments sampled. The Methylococcaceae are also less diverse in forest soil compared to the other two habitats. Nonmetric multidimensional scaling analyses indicated that the majority of methanotrophs from the Methylococcaceae and Methylocystaceae tend to occur in one habitat only (peat or Sphagnum moss) or co-occurred in both Sphagnum moss and peat. This study provides insights into the structure of methanotrophic communities in relationship to habitat type, and suggests that peat and Sphagnum moss can influence methanotroph community structure and biogeography. PMID- 27682083 TI - Interactions of Methylotrophs with Plants and Other Heterotrophic Bacteria. AB - Methylotrophs, which can utilize methane and/or methanol as sole carbon and energy sources, are key players in the carbon cycle between methane and CO2, the two most important greenhouse gases. This review describes the relationships between methylotrophs and plants, and between methanotrophs (methane-utilizers, a subset of methylotrophs) and heterotrophic bacteria. Some plants emit methane and methanol from their leaves, and provide methylotrophs with habitats. Methanol utilizing methylotrophs in the genus Methylobacterium are abundant in the phyllosphere and have the ability to promote the growth of some plants. Methanotrophs also inhabit the phyllosphere, and methanotrophs with high methane oxidation activities have been found on aquatic plants. Both plant and environmental factors are involved in shaping the methylotroph community on plants. Methanotrophic activity can be enhanced by heterotrophic bacteria that provide growth factors (e.g., cobalamin). Information regarding the biological interaction of methylotrophs with other organisms will facilitate a better understanding of the carbon cycle that is driven by methylotrophs. PMID- 27682084 TI - Parallel and Divergent Evolutionary Solutions for the Optimization of an Engineered Central Metabolism in Methylobacterium extorquens AM1. AB - Bioengineering holds great promise to provide fast and efficient biocatalysts for methanol-based biotechnology, but necessitates proven methods to optimize physiology in engineered strains. Here, we highlight experimental evolution as an effective means for optimizing an engineered Methylobacterium extorquens AM1. Replacement of the native formaldehyde oxidation pathway with a functional analog substantially decreased growth in an engineered Methylobacterium, but growth rapidly recovered after six hundred generations of evolution on methanol. We used whole-genome sequencing to identify the basis of adaptation in eight replicate evolved strains, and examined genomic changes in light of other growth and physiological data. We observed great variety in the numbers and types of mutations that occurred, including instances of parallel mutations at targets that may have been "rationalized" by the bioengineer, plus other "illogical" mutations that demonstrate the ability of evolution to expose unforeseen optimization solutions. Notably, we investigated mutations to RNA polymerase, which provided a massive growth benefit but are linked to highly aberrant transcriptional profiles. Overall, we highlight the power of experimental evolution to present genetic and physiological solutions for strain optimization, particularly in systems where the challenges of engineering are too many or too difficult to overcome via traditional engineering methods. PMID- 27682085 TI - C1-Pathways in Methyloversatilis universalis FAM5: Genome Wide Gene Expression and Mutagenesis Studies. AB - Methyloversatilis universalis FAM5 utilizes single carbon compounds such as methanol or methylamine as a sole source of carbon and energy. Expression profiling reveals distinct sets of genes altered during growth on methylamine vs methanol. As expected, all genes for the N-methylglutamate pathway were induced during growth on methylamine. Among other functions responding to the aminated source of C1-carbon, are a heme-containing amine dehydrogenase (Qhp), a distant homologue of formaldehyde activating enzyme (Fae3), molybdenum-containing formate dehydrogenase, ferredoxin reductase, a set of homologues to urea/ammonium transporters and amino-acid permeases. Mutants lacking one of the functional subunits of the amine dehydrogenase (DeltaqhpA) or Deltafae3 showed no growth defect on C1-compounds. M. universalis FAM5 strains with a lesion in the H4 folate pathway were not able to use any C1-compound, methanol or methylamine. Genes essential for C1-assimilation (the serine cycle and glyoxylate shunt) and H4MTP-pathway for formaldehyde oxidation showed similar levels of expression on both C1-carbon sources. M. universalis FAM5 possesses three homologs of the formaldehyde activating enzyme, a key enzyme of the H4MTP-pathway. Strains lacking the canonical Fae (fae1) lost the ability to grow on both C1-compounds. However, upon incubation on methylamine the fae1-mutant produced revertants (Deltafae1(R)), which regained the ability to grow on methylamine. Double and triple mutants (Deltafae1(R)Deltafae3, or Deltafae1(R)Deltafae2 or Deltafae1(R)Deltafae2Deltafae3) constructed in the revertant strain background showed growth similar to the Deltafae1(R) phenotype. The metabolic pathways for utilization of methanol and methylamine in Methyloversatilis universalis FAM5 are reconstructed based on these gene expression and phenotypic data. PMID- 27682086 TI - Comparison of Microbiological and Probiotic Characteristics of Lactobacilli Isolates from Dairy Food Products and Animal Rumen Contents. AB - Lactobacilli are employed in probiotic food preparations and as feed additives in poultry and livestock, due to health benefits associated with their consumption. The objective of this study was to evaluate and compare the probiotic potential of ten lactobacilli strains isolated from commercial dairy food products and animal rumen contents in New Zealand. Genetic identification of the isolates revealed that all belonged to the genus Lactobacillus, specifically the species L. reuteri, L. rhamnosus and L. plantarum. All isolates did not show any haemolytic behaviour. Isolates of dairy origin showed better tolerance to low pH stress. On the other hand, rumen isolates exhibited a higher tolerance to presence of bile salts. All isolates exhibited resistance to aminoglycoside antibiotics, however most were sensitive to ampicillin. Isolates of rumen origin demonstrated a higher inhibitory effect on Listeria monocytogenes, Enterobacter aerogenes and Salmonella menston. Bacterial adherence of all isolates increased with a decrease in pH. This screening study on lactobacilli isolates has assessed and identified potential probiotic candidates for further evaluation. PMID- 27682089 TI - Generation of PHB from Spent Sulfite Liquor Using Halophilic Microorganisms. AB - Halophilic microorganisms thrive at elevated concentrations of sodium chloride up to saturation and are capable of growing on a wide variety of carbon sources like various organic acids, hexose and also pentose sugars. Hence, the biotechnological application of these microorganisms can cover many aspects, such as the treatment of hypersaline waste streams of different origin. Due to the fact that the high osmotic pressure of hypersaline environments reduces the risk of contamination, the capacity for cost-effective non-sterile cultivation can make extreme halophilic microorganisms potentially valuable organisms for biotechnological applications. In this contribution, the stepwise use of screening approaches, employing design of experiment (DoE) on model media and subsequently using industrial waste as substrate have been implemented to investigate the applicability of halophiles to generate PHB from the industrial waste stream spent sulfite liquor (SSL). The production of PHB on model media as well as dilutions of industrial substrate in a complex medium has been screened for by fluorescence microscopy using Nile Blue staining. Screening was used to investigate the ability of halophilic microorganisms to withstand the inhibiting substances of the waste stream without negatively affecting PHB production. It could be shown that neither single inhibiting substances nor a mixture thereof inhibited growth in the investigated range, hence, leaving the question on the inhibiting mechanisms open. However, it could be demonstrated that some haloarchaea and halophilic bacteria are able to produce PHB when cultivated on 3.3% w/w dry matter spent sulfite liquor, whereas H. halophila was even able to thrive on 6.6% w/w dry matter spent sulfite liquor and still produce PHB. PMID- 27682087 TI - Does the Gut Microbiota Contribute to Obesity? Going beyond the Gut Feeling. AB - Increasing evidence suggests that gut microbiota is an environmental factor that plays a crucial role in obesity. However, the aetiology of obesity is rather complex and depends on different factors. Furthermore, there is a lack of consensus about the exact role that this microbial community plays in the host. The aim of this review is to present evidence about what has been characterized, compositionally and functionally, as obese gut microbiota. In addition, the different reasons explaining the so-far unclear role are discussed considering evidence from in vitro, animal and human studies. PMID- 27682090 TI - Methane Oxidation and Molecular Characterization of Methanotrophs from a Former Mercury Mine Impoundment. AB - The Herman Pit, once a mercury mine, is an impoundment located in an active geothermal area. Its acidic waters are permeated by hundreds of gas seeps. One seep was sampled and found to be composed of mostly CO2 with some CH4 present. The delta(13)CH4 value suggested a complex origin for the methane: i.e., a thermogenic component plus a biological methanogenic portion. The relatively (12)C-enriched CO2 suggested a reworking of the ebullitive methane by methanotrophic bacteria. Therefore, we tested bottom sediments for their ability to consume methane by conducting aerobic incubations of slurried materials. Methane was removed from the headspace of live slurries, and subsequent additions of methane resulted in faster removal rates. This activity could be transferred to an artificial, acidic medium, indicating the presence of acidophilic or acid tolerant methanotrophs, the latter reinforced by the observation of maximum activity at pH = 4.5 with incubated slurries. A successful extraction of sterol and hopanoid lipids characteristic of methanotrophs was achieved, and their abundances greatly increased with increased sediment methane consumption. DNA extracted from methane-oxidizing enrichment cultures was amplified and sequenced for pmoA genes that aligned with methanotrophic members of the Gammaproteobacteria. An enrichment culture was established that grew in an acidic (pH 4.5) medium via methane oxidation. PMID- 27682091 TI - Temporal Study of the Microbial Diversity of the North Arm of Great Salt Lake, Utah, U.S. AB - We employed a temporal sampling approach to understand how the microbial diversity may shift in the north arm of Great Salt Lake, Utah, U.S. To determine how variations in seasonal environmental factors affect microbial communities, length heterogeneity PCR fingerprinting was performed using consensus primers for the domain Bacteria, and the haloarchaea. The archaeal fingerprints showed similarities during 2003 and 2004, but this diversity changed during the remaining two years of the study, 2005 and 2006. We also performed molecular phylogenetic analysis of the 16S rRNA genes of the whole microbial community to characterize the taxa in the samples. Our results indicated that in the domain, Bacteria, the Salinibacter group dominated the populations in all samplings. However, in the case of Archaea, as noted by LIBSHUFF for phylogenetic relatedness analysis, many of the temporal communities were distinct from each other, and changes in community composition did not track with environmental parameters. Around 20-23 different phylotypes, as revealed by rarefaction, predominated at different periods of the year. Some phylotypes, such as Haloquadradum, were present year-round although they changed in their abundance in different samplings, which may indicate that these species are affected by biotic factors, such as nutrients or viruses, that are independent of seasonal temperature dynamics. PMID- 27682092 TI - Tetrachloromethane-Degrading Bacterial Enrichment Cultures and Isolates from a Contaminated Aquifer. AB - The prokaryotic community of a groundwater aquifer exposed to high concentrations of tetrachloromethane (CCl4) for more than three decades was followed by terminal restriction fragment length polymorphism (T-RFLP) during pump-and-treat remediation at the contamination source. Bacterial enrichments and isolates were obtained under selective anoxic conditions, and degraded 10 mg.L(-1) CCl4, with less than 10% transient formation of chloroform. Dichloromethane and chloromethane were not detected. Several tetrachloromethane-degrading strains were isolated from these enrichments, including bacteria from the Klebsiella and Clostridium genera closely related to previously described CCl4 degrading bacteria, and strain TM1, assigned to the genus Pelosinus, for which this property was not yet described. Pelosinus sp. TM1, an oxygen-tolerant, Gram positive bacterium with strictly anaerobic metabolism, excreted a thermostable metabolite into the culture medium that allowed extracellular CCl4 transformation. As estimated by T-RFLP, phylotypes of CCl4-degrading enrichment cultures represented less than 7%, and archaeal and Pelosinus strains less than 0.5% of the total prokaryotic groundwater community. PMID- 27682093 TI - Copahue Geothermal System: A Volcanic Environment with Rich Extreme Prokaryotic Biodiversity. AB - The Copahue geothermal system is a natural extreme environment located at the northern end of the Cordillera de los Andes in Neuquen province in Argentina. The geochemistry and consequently the biodiversity of the area are dominated by the activity of the Copahue volcano. The main characteristic of Copahue is the extreme acidity of its aquatic environments; ponds and hot springs of moderate and high temperature as well as Rio Agrio. In spite of being an apparently hostile location, the prokaryotic biodiversity detected by molecular ecology techniques as well as cultivation shows a rich and diverse environment dominated by acidophilic, sulphur oxidising bacteria or archaea, depending on the conditions of the particular niche studied. In microbial biofilms, found in the borders of the ponds where thermal activity is less intense, the species found are completely different, with a high presence of cyanobacteria and other photosynthetic species. Our results, collected during more than 10 years of work in Copahue, have enabled us to outline geomicrobiological models for the different environments found in the ponds and Rio Agrio. Besides, Copahue seems to be the habitat of novel, not yet characterised autochthonous species, especially in the domain Archaea. PMID- 27682094 TI - Extremophiles in Mineral Sulphide Heaps: Some Bacterial Responses to Variable Temperature, Acidity and Solution Composition. AB - In heap bioleaching, acidophilic extremophiles contribute to enhanced metal extraction from mineral sulphides through the oxidation of Fe(II) and/or reduced inorganic sulphur compounds (RISC), such as elemental sulphur or mineral sulphides, or the degradation of organic compounds derived from the ore, biota or reagents used during mineral processing. The impacts of variable solution acidity and composition, as well as temperature on the three microbiological functions have been examined for up to four bacterial species found in mineral sulphide heaps. The results indicate that bacteria adapt to sufficiently high metal concentrations (Cu, Ni, Co, Zn, As) to allow them to function in mineral sulphide heaps and, by engaging alternative metabolic pathways, to extend the solution pH range over which growth is sustained. Fluctuating temperatures during start up in sulphide heaps pose the greatest threat to efficient bacterial colonisation. The large masses of ores in bioleaching heaps mean that high temperatures arising from sulphide oxidation are hard to control initially, when the sulphide content of the ore is greatest. During that period, mesophilic and moderately thermophilic bacteria are markedly reduced in both numbers and activity. PMID- 27682088 TI - Tackling Drug Resistant Infection Outbreaks of Global Pandemic Escherichia coli ST131 Using Evolutionary and Epidemiological Genomics. AB - High-throughput molecular screening is required to investigate the origin and diffusion of antimicrobial resistance in pathogen outbreaks. The most frequent cause of human infection is Escherichia coli, which is dominated by sequence type 131 (ST131)-a set of rapidly radiating pandemic clones. The highly infectious clades of ST131 originated firstly by a mutation enhancing conjugation and adhesion. Secondly, single-nucleotide polymorphisms occurred enabling fluoroquinolone-resistance, which is near-fixed in all ST131. Thirdly, broader resistance through beta-lactamases has been gained and lost frequently, symptomatic of conflicting environmental selective effects. This flexible approach to gene exchange is worrying and supports the proposition that ST131 will develop an even wider range of plasmid and chromosomal elements promoting antimicrobial resistance. To stop ST131, deep genome sequencing is required to understand the origin, evolution and spread of antimicrobial resistance genes. Phylogenetic methods that decipher past events can predict future patterns of virulence and transmission based on genetic signatures of adaptation and gene exchange. Both the effect of partial antimicrobial exposure and cell dormancy caused by variation in gene expression may accelerate the development of resistance. High-throughput sequencing can decode measurable evolution of cell populations within patients associated with systems-wide changes in gene expression during treatments. A multi-faceted approach can enhance assessment of antimicrobial resistance in E. coli ST131 by examining transmission dynamics between hosts to achieve a goal of pre-empting resistance before it emerges by optimising antimicrobial treatment protocols. PMID- 27682095 TI - Cold-Active, Heterotrophic Bacteria from the Highly Oligotrophic Waters of Lake Vanda, Antarctica. AB - The permanently ice-covered lakes of the McMurdo Dry Valleys, Antarctica are distinctive ecosystems that consist strictly of microbial communities. In this study, water samples were collected from Lake Vanda, a stratified Dry Valley lake whose upper waters (from just below the ice cover to nearly 60 m) are highly oligotrophic, and used to establish enrichment cultures. Six strains of psychrotolerant, heterotrophic bacteria were isolated from lake water samples from a depth of 50 or 55 m. Phylogenetic analyses showed the Lake Vanda strains to be species of Nocardiaceae, Caulobacteraceae, Sphingomonadaceae, and Bradyrhizobiaceae. All Lake Vanda strains grew at temperatures near or below 0 degrees C, but optimal growth occurred from 18 to 24 degrees C. Some strains showed significant halotolerance, but no strains required NaCl for growth. The isolates described herein include cold-active species not previously reported from Dry Valley lakes, and their physiological and phylogenetic characterization broadens our understanding of these limnologically unique lakes. PMID- 27682097 TI - Live Yeast and Yeast Cell Wall Supplements Enhance Immune Function and Performance in Food-Producing Livestock: A Review (?,)(?). AB - More livestock producers are seeking natural alternatives to antibiotics and antimicrobials, and searching for supplements to enhance growth performance, and general animal health and well-being. Some of the compounds currently being utilized and studied are live yeast and yeast-based products derived from the strain Saccharomyces cerevisiae. These products have been reported to have positive effects both directly and indirectly on the immune system and its subsequent biomarkers, thereby mitigating negative effects associated with stress and disease. These yeast-based products have also been reported to simultaneously enhance growth and performance by enhancing dry matter intake (DMI) and average daily gain (ADG) perhaps through the establishment of a healthy gastrointestinal tract. These products may be especially useful in times of potential stress such as during birth, weaning, early lactation, and during the receiving period at the feedlot. Overall, yeast supplements appear to possess the ability to improve animal health and metabolism while decreasing morbidity, thereby enhancing profitability of these animals. PMID- 27682096 TI - Pyruvate: A key Nutrient in Hypersaline Environments? AB - Some of the most commonly occurring but difficult to isolate halophilic prokaryotes, Archaea as well as Bacteria, require or prefer pyruvate as carbon and energy source. The most efficient media for the enumeration and isolation of heterotrophic prokaryotes from natural environments, from freshwater to hypersaline, including the widely used R2A agar medium, contain pyruvate as a key ingredient. Examples of pyruvate-loving halophiles are the square, extremely halophilic archaeon Haloquadratum walsbyi and the halophilic gammaproteobacterium Spiribacter salinus. However, surprisingly little is known about the availability of pyruvate in natural environments and about the way it enters the cell. Some halophilic Archaea (Halorubrum saccharovorum, Haloarcula spp.) partially convert sugars and glycerol to pyruvate and other acids (acetate, lactate) which are excreted to the medium. Pyruvate formation from glycerol was also shown during a bloom of halophilic Archaea in the Dead Sea. However, no pyruvate transporters were yet identified in the genomes of halophilic Archaea, and altogether, our understanding of pyruvate transport in the prokaryote world is very limited. Therefore, the preference for pyruvate by fastidious and often elusive halophiles and the empirically proven enhanced colony recovery on agar media containing pyruvate are still poorly understood. PMID- 27682099 TI - Quantitative Characterization of the Growth of Deinococcus geothermalis DSM 11302: Effect of Inoculum Size, Growth Medium and Culture Conditions. AB - Due to their remarkable resistance to extreme conditions, Deinococcaceae strains are of great interest to biotechnological prospects. However, the physiology of the extremophile strain Deinococcus geothermalis has scarcely been studied and is not well understood. The physiological behaviour was then studied in well controlled conditions in flask and bioreactor cultures. The growth of D. geothermalis type strains was compared. Among the strains tested, the strain from the German Collection of Microorganisms (Deutsche Sammlung von Mikroorganismen DSM) DSM-11302 was found to give the highest biomass concentration and growth rate: in a complex medium with glucose, the growth rate reached 0.75 h(-1) at 45 degrees C. Yeast extract concentration in the medium had significant constitutive and catalytic effects. Furthermore, the results showed that the physiological descriptors were not affected by the inoculum preparation steps. A batch culture of D. geothermalis DSM-11302 on defined medium was carried out: cells grew exponentially with a maximal growth rate of 0.28 h(-1) and D. geothermalis DSM 11302 biomass reached 1.4 g.L(-1) in 20 h. Then, 1.4 gDryCellWeight of biomass (X) was obtained from 5.6 g glucose (Glc) consumed as carbon source, corresponding to a yield of 0.3 CmolX.CmolGlc(-1); cell specific oxygen uptake and carbon dioxide production rates reached 216 and 226 mmol.CmolX(-1).h(-1), respectively, and the respiratory quotient (QR) value varied from 1.1 to 1.7. This is the first time that kinetic parameters and yields are reported for D. geothermalis DSM-11302 grown on a mineral medium in well-controlled batch culture. PMID- 27682098 TI - Assessment of the Factors Contributing to the Growth or Spoilage of Meyerozyma guilliermondii in Organic Yogurt: Comparison of Methods for Strain Differentiation. AB - In this work we analyze the spoiling potential of Meyerozyma guilliermondii in yogurt. The analysis was based on contaminated samples sent to us by an industrial laboratory over two years. All the plain and fruit yogurt packages were heavily contaminated by yeasts, but only the last ones, containing fermentable sugars besides lactose, were spoiled by gas swelling. These strains were unable to grow and ferment lactose (as the type strain); they did grow on lactate plus galactose, fermented glucose and sucrose, and galactose (weakly), but did not compete with lactic acid bacteria for lactose. This enables them to grow in any yogurt, although only those with added jam were spoiled due to the fermentation of the fruit sugars. Fermentation, but not growth, was strongly inhibited at 8 degrees C. In consequence, in plain yogurt as well as in any yogurt maintained at low temperature, yeast contamination would not be detected by the consumer. The risk could be enhanced because the species has been proposed for biological control of fungal infections in organic agriculture. The combination of the IGS PCR-RFLP (amplification of the intergenic spacer region of rDNA followed by restriction fragment length polymorphism analysis) method and mitochondrial DNA-RFLP makes a good tool to trace and control the contamination by M. guilliermondii. PMID- 27682100 TI - Role of Bacterial Exopolysaccharides as Agents in Counteracting Immune Disorders Induced by Herpes Virus. AB - Extreme marine environments, such as the submarine shallow vents of the Eolian Islands (Italy), offer an almost unexplored source of microorganisms producing unexploited and promising biomolecules for pharmaceutical applications. Thermophilic and thermotolerant bacilli isolated from Eolian vents are able to produce exopolysaccharides (EPSs) with antiviral and immunomodulatory effects against Herpes simplex virus type 2 (HSV-2). HSV-2 is responsible for the most common and continuously increasing viral infections in humans. Due to the appearance of resistance to the available treatments, new biomolecules exhibiting different mechanisms of action could provide novel agents for treating viral infections. The EPSs hinder the HSV-2 replication in human peripheral blood mononuclear cells (PBMC) but not in WISH (Wistar Institute Susan Hayflic) cells line, indicating that cell-mediated immunity was involved in the antiviral activity. High levels of Th1-type cytokines were detected in PBMC treated with all EPSs, while Th2-type cytokines were not induced. These EPSs are water soluble exopolymers able to stimulate the immune response and thus contribute to the antiviral immune defense, acting as immunomodulators. As stimulants of Th1 cell mediated immunity, they could lead to the development of novel drugs as alternative in the treatment of herpes virus infections, as well as in immunocompromised host. PMID- 27682101 TI - Novel Methanotrophs of the Family Methylococcaceae from Different Geographical Regions and Habitats. AB - Terrestrial methane seeps and rice paddy fields are important ecosystems in the methane cycle. Methanotrophic bacteria in these ecosystems play a key role in reducing methane emission into the atmosphere. Here, we describe three novel methanotrophs, designated BRS-K6, GFS-K6 and AK-K6, which were recovered from three different habitats in contrasting geographic regions and ecosystems: waterlogged rice-field soil and methane seep pond sediments from Bangladesh; and warm spring sediments from Armenia. All isolates had a temperature range for growth of 8-35 degrees C (optimal 25-28 degrees C) and a pH range of 5.0-7.5 (optimal 6.4-7.0). 16S rRNA gene sequences showed that they were new gammaproteobacterial methanotrophs, which form a separate clade in the family Methylococcaceae. They fell into a cluster with thermotolerant and mesophilic growth tendency, comprising the genera Methylocaldum-Methylococcus Methyloparacoccus-Methylogaea. So far, growth below 15 degrees C of methanotrophs from this cluster has not been reported. The strains possessed type I intracytoplasmic membranes. The genes pmoA, mxaF, cbbL, nifH were detected, but no mmoX gene was found. Each strain probably represents a novel species either belonging to the same novel genus or each may even represent separate genera. These isolates extend our knowledge of methanotrophic Gammaproteobacteria and their physiology and adaptation to different ecosystems. PMID- 27682104 TI - Effect of Lemongrass Essential Oil Vapors on Microbial Dynamics and Listeria monocytogenes Survival on Rocket and Melon Stored under Different Packaging Conditions and Temperatures. AB - The aim of the present study was to examine the effect of lemongrass essential oil vapors on the dynamics of surface microbiota and L. monocytogenes growth on rocket and melon under different packaging conditions and storage temperature. For that purpose, rocket and melon were placed on Expanded Polystyrene (EPS) trays, sprayed with L. monocytogenes to a population of 4.5-5.0 log CFU.g(-1), packaged using microperforated Oriented Polypropylene (OPP) film in either air or Microperforated Active Modified Atmosphere (MAMA) (initial atmosphere 5% O2, 10% CO2) including a Whatman paper containing the essential oil, without contact with the product, and stored at 0, 5, 10, and 15 degrees C. Application of lemongrass exhibited a bactericidal effect on enterococci and a fungistatic effect on yeast mould populations but only during air storage of rocket. The former took place at all temperatures and the latter only at 10 and 15 degrees C. No effect on shelf life of both products was recorded. However, an important effect on the sensorial properties was observed; during the first 4-5 days of storage both products were organoleptically unacceptable. Regarding MAMA packaging, it affected only Pseudomonas spp. population resulting in a reduction of 1-2 log CFU.g(-1) in both products. PMID- 27682102 TI - A Three-Component Microbial Consortium from Deep-Sea Salt-Saturated Anoxic Lake Thetis Links Anaerobic Glycine Betaine Degradation with Methanogenesis. AB - Microbial communities inhabiting the deep-sea salt-saturated anoxic lakes of the Eastern Mediterranean operate under harsh physical-chemical conditions that are incompatible with the lifestyle of common marine microorganisms. Here, we investigated a stable three-component microbial consortium obtained from the brine of the recently discovered deep-sea salt-saturated Lake Thetis. The trophic network of this consortium, established at salinities up to 240, relies on fermentative decomposition of common osmoprotectant glycine betaine (GB). Similarly to known extreme halophilic anaerobic GB-degrading enrichments, the initial step of GB degradation starts with its reductive cleavage to trimethylamine and acetate, carried out by the fermenting member of the Thetis enrichment, Halobacteroides lacunaris TB21. In contrast to acetate, which cannot be easily oxidized in salt-saturated anoxic environments, trimethylamine represents an advantageous C1-substrate for methylotrophic methanogenic member of the Thetis enrichment, Methanohalophilus sp. TA21. This second member of the consortium likely produces hydrogen via methylotrophic modification of reductive acetyl-CoA pathway because the initial anaerobic GB cleavage reaction requires the consumption of reducing equivalents. Ecophysiological role of the third member of the Thetis consortium, Halanaerobium sp. TB24, which lacks the capability of either GB or trimethylamine degradation, remains yet to be elucidated. As it is true for cultivated members of family Halanaerobiaceae, the isolate TB24 can obtain energy primarily by fermenting simple sugars and producing hydrogen as one of the end products. Hence, by consuming of TB21 and TA21 metabolites, Halanaerobium sp. TB24 can be an additional provider of reducing equivalents required for reductive degradation of GB. Description of the Thetis GB-degrading consortium indicated that anaerobic degradation of osmoregulatory molecules may play important role in the overall turnover of organic carbon in anoxic hypersaline biotopes. PMID- 27682105 TI - Evaluation of Potential Effects of NaCl and Sorbic Acid on Staphylococcal Enterotoxin A Formation. AB - The prophage-encoded staphylococcal enterotoxin A (SEA) is recognized as the main cause of staphylococcal food poisoning (SFP), a common foodborne intoxication disease, caused by Staphylococcus aureus. Studies on the production of SEA suggest that activation of the SOS response and subsequent prophage induction affect the regulation of the sea gene and the SEA produced, increasing the risk for SFP. The present study aims to evaluate the effect of NaCl and sorbic acid, in concentrations relevant to food production, on SOS response activation, prophage induction and SEA production. The impact of stress was initially evaluated on steady state cells for a homogenous cell response. NaCl 2% was found to activate the SOS response, i.e., recA expression, and trigger prophage induction, in a similar way as the phage-inducer mitomycin C. In contrast, sorbic acid decreased the pH of the culture to a level where prophage induction was probably suppressed, even when combined with NaCl stress. The impact of previous physiological state of the bacteria was also addressed on cells pre-exposed to NaCl, and was found to potentially affect cell response upon exposure to further stress. The results obtained highlight the possible SFP-related risks arising from the use of preservatives during food processing. PMID- 27682103 TI - The Effects of Perchlorates on the Permafrost Methanogens: Implication for Autotrophic Life on Mars. AB - The terrestrial permafrost represents a range of possible cryogenic extraterrestrial ecosystems on Earth-like planets without obvious surface ice, such as Mars. The autotrophic and chemolithotrophic psychrotolerant methanogens are more likely than aerobes to function as a model for life forms that may exist in frozen subsurface environments on Mars, which has no free oxygen, inaccessible organic matter, and extremely low amounts of unfrozen water. Our research on the genesis of methane, its content and distribution in permafrost horizons of different ages and origin demonstrated the presence of methane in permanently frozen fine-grained sediments. Earlier, we isolated and described four strains of methanogenic archaea of Methanobacterium and Methanosarcina genera from samples of Pliocene and Holocene permafrost from Eastern Siberia. In this paper we study the effect of sodium and magnesium perchlorates on growth of permafrost and nonpermafrost methanogens, and present evidence that permafrost hydogenotrophic methanogens are more resistant to the chaotropic agent found in Martian soil. In this paper we study the effect of sodium and magnesium perchlorates on the growth of permafrost and nonpermafrost methanogens, and present evidence that permafrost hydogenotrophic methanogens are more resistant to the chaotropic agent found in Martian soil. Furthermore, as shown in the studies strain M2(T) M. arcticum, probably can use perchlorate anion as an electron acceptor in anaerobic methane oxidation. Earth's subzero subsurface environments are the best approximation of environments on Mars, which is most likely to harbor methanogens; thus, a biochemical understanding of these pathways is expected to provide a basis for designing experiments to detect autotrophic methane-producing life forms on Mars. PMID- 27682106 TI - Membrane Association and Catabolite Repression of the Sulfolobus solfataricus alpha-Amylase. AB - Sulfolobus solfataricus is a thermoacidophilic member of the archaea whose envelope consists of an ether-linked lipid monolayer surrounded by a protein S layer. Protein translocation across this envelope must accommodate a steep proton gradient that is subject to temperature extremes. To better understand this process in vivo, studies were conducted on the S. solfataricus glycosyl hydrolyase family 57 alpha-Amylase (AmyA). Cell lines harboring site specific modifications of the amyA promoter and AmyA structural domains were created by gene replacement using markerless exchange and characterized by Western blot, enzyme assay and culture-based analysis. Fusion of amyA to the malAp promoter overcame amyAp-mediated regulatory responses to media composition including glucose and amino acid repression implicating action act at the level of transcription. Deletion of the AmyA Class II N-terminal signal peptide blocked protein secretion and intracellular protein accumulation. Deletion analysis of a conserved bipartite C-terminal motif consisting of a hydrophobic region followed by several charged residues indicated the charged residues played an essential role in membrane-association but not protein secretion. Mutants lacking the C terminal bipartite motif exhibited reduced growth rates on starch as the sole carbon and energy source; therefore, association of AmyA with the membrane improves carbohydrate utilization. Widespread occurrence of this motif in other secreted proteins of S. solfataricus and of related Crenarchaeota suggests protein association with membranes is a general trait used by these organisms to influence external processes. PMID- 27682108 TI - Fungal Biodiversity in the Alpine Tarfala Valley. AB - Biological soil crusts (BSCs) are distributed worldwide in all semiarid and arid lands, where they play a determinant role in element cycling and soil development. Although much work has concentrated on BSC microbial communities, free-living fungi have been hitherto largely overlooked. The aim of this study was to examine the fungal biodiversity, by cultural-dependent and cultural independent approaches, in thirteen samples of Arctic BSCs collected at different sites in the Alpine Tarfala Valley, located on the slopes of Kebnekaise, the highest mountain in northern Scandinavia. Isolated fungi were identified by both microscopic observation and molecular approaches. Data revealed that the fungal assemblage composition was homogeneous among the BSCs analyzed, with low biodiversity and the presence of a few dominant species; the majority of fungi isolated belonged to the Ascomycota, and Cryptococcus gilvescens and Pezoloma ericae were the most frequently-recorded species. Ecological considerations for the species involved and the implication of our findings for future fungal research in BSCs are put forward. PMID- 27682107 TI - Bioprotective Role of Yeasts. AB - The yeasts constitute a large group of microorganisms characterized by the ability to grow and survive in different and stressful conditions and then to colonize a wide range of environmental and human ecosystems. The competitive traits against other microorganisms have attracted increasing attention from scientists, who proposed their successful application as bioprotective agents in the agricultural, food and medical sectors. These antagonistic activities rely on the competition for nutrients, production and tolerance of high concentrations of ethanol, as well as the synthesis of a large class of antimicrobial compounds, known as killer toxins, which showed clearly a large spectrum of activity against food spoilage microorganisms, but also against plant, animal and human pathogens. This review describes the antimicrobial mechanisms involved in the antagonistic activity, their applications in the processed and unprocessed food sectors, as well as the future perspectives in the development of new bio-drugs, which may overcome the limitations connected to conventional antimicrobial and drug resistance. PMID- 27682109 TI - Alicyclobacillus spp.: New Insights on Ecology and Preserving Food Quality through New Approaches. AB - Alicyclobacillus spp. includes spore-forming and thermo-acidophilic microorganisms, usually recovered from soil, acidic drinks, orchards and equipment from juice producers. The description of the genus is generally based on the presence of omega-fatty acids in the membrane, although some newly described species do not possess them. The genus includes different species and sub-species, but A. acidoterrestris is generally regarded as the most important spoiler for acidic drinks and juices. The main goal of this review is a focus on the ecology of the genus, mainly on the species A. acidoterrestris, with a special emphasis on the different phenotypic properties and genetic traits, along with the correlation among them and with the primary source of isolation. Finally, the last section of the review reports on some alternative approaches to heat treatments (natural compounds and other chemical treatments) to control and/or reduce the contamination of food by Alicyclobacillus. PMID- 27682112 TI - How to Show the Real Microbial Biodiversity? A Comparison of Seven DNA Extraction Methods for Bacterial Population Analyses in Matrices Containing Highly Charged Natural Nanoparticles. AB - A DNA extraction that comprises the DNA of all available taxa in an ecosystem is an essential step in population analysis, especially for next generation sequencing applications. Many nanoparticles as well as naturally occurring clay minerals contain charged surfaces or edges that capture negatively charged DNA molecules after cell lysis within DNA extraction. Depending on the methodology of DNA extraction, this phenomenon causes a shift in detection of microbial taxa in ecosystems and a possible misinterpretation of microbial interactions. With the aim to describe microbial interactions and the bio-geo-chemical reactions during a clay alteration experiment, several methods for the detection of a high number of microbial taxa were examined in this study. Altogether, 13 different methods of commercially available DNA extraction kits provided by seven companies as well as the classical phenol-chloroform DNA extraction were compared. The amount and the quality of nucleic acid extracts were determined and compared to the amplifiable amount of DNA. The 16S rRNA gene fragments of several taxa were separated using denaturing gradient gel electrophoresis (DGGE) to determine the number of different species and sequenced to get the information about what kind of species the microbial population consists of. A total number of 13 species was detected in the system. Up to nine taxa could be detected with commercially available DNA extraction kits while phenol-chloroform extraction lead to three detected species. In this paper, we describe how to combine several DNA extraction methods for the investigation of microbial community structures in clay. PMID- 27682111 TI - Novel and Unexpected Microbial Diversity in Acid Mine Drainage in Svalbard (78 degrees N), Revealed by Culture-Independent Approaches. AB - Svalbard, situated in the high Arctic, is an important past and present coal mining area. Dozens of abandoned waste rock piles can be found in the proximity of Longyearbyen. This environment offers a unique opportunity for studying the biological control over the weathering of sulphide rocks at low temperatures. Although the extension and impact of acid mine drainage (AMD) in this area is known, the native microbial communities involved in this process are still scarcely studied and uncharacterized. Several abandoned mining areas were explored in the search for active AMD and a culture-independent approach was applied with samples from two different runoffs for the identification and quantification of the native microbial communities. The results obtained revealed two distinct microbial communities. One of the runoffs was more extreme with regards to pH and higher concentration of soluble iron and heavy metals. These conditions favored the development of algal-dominated microbial mats. Typical AMD microorganisms related to known iron-oxidizing bacteria (Acidithiobacillus ferrivorans, Acidobacteria and Actinobacteria) dominated the bacterial community although some unexpected populations related to Chloroflexi were also significant. No microbial mats were found in the second area. The geochemistry here showed less extreme drainage, most likely in direct contact with the ore under the waste pile. Large deposits of secondary minerals were found and the presence of iron stalks was revealed by microscopy analysis. Although typical AMD microorganisms were also detected here, the microbial community was dominated by other populations, some of them new to this type of system (Saccharibacteria, Gallionellaceae). These were absent or lowered in numbers the farther from the spring source and they could represent native populations involved in the oxidation of sulphide rocks within the waste rock pile. This environment appears thus as a highly interesting field of potential novelty in terms of both phylogenetic/taxonomic and functional diversity. PMID- 27682110 TI - The Gut Microbiota as a Therapeutic Target in IBD and Metabolic Disease: A Role for the Bile Acid Receptors FXR and TGR5. AB - The gut microbiota plays a crucial role in regulating many physiological systems of the host, including the metabolic and immune system. Disturbances in microbiota composition are increasingly correlated with disease; however, the underlying mechanisms are not well understood. Recent evidence suggests that changes in microbiota composition directly affect the metabolism of bile salts. Next to their role in digestion of dietary fats, bile salts function as signaling molecules for bile salt receptors such as Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5). Complementary to their role in metabolism, FXR and TGR5 are shown to play a role in intestinal homeostasis and immune regulation. This review presents an overview of evidence showing that changes in bile salt pool and composition due to changes in gut microbial composition contribute to the pathogenesis of inflammatory bowel disease and metabolic disease, possibly through altered activation of TGR5 and FXR. We further discuss how dietary interventions, such as pro- and synbiotics, may be used to treat metabolic disease and inflammatory bowel disease (IBD) through normalization of bile acid dysregulation directly or indirectly through normalization of the intestinal microbiota. PMID- 27682113 TI - Sulfur Oxygenase Reductase (Sor) in the Moderately Thermoacidophilic Leaching Bacteria: Studies in Sulfobacillus thermosulfidooxidans and Acidithiobacillus caldus. AB - The sulfur oxygenase reductase (Sor) catalyzes the oxygen dependent disproportionation of elemental sulfur, producing sulfite, thiosulfate and sulfide. Being considered an "archaeal like" enzyme, it is also encoded in the genomes of some acidophilic leaching bacteria such as Acidithiobacillus caldus, Acidithiobacillus thiooxidans, Acidithiobacillus ferrivorans and Sulfobacillus thermosulfidooxidans, among others. We measured Sor activity in crude extracts from Sb. thermosulfidooxidans DSM 9293(T). The optimum temperature for its oxygenase activity was achieved at 75 degrees C, confirming the "thermophilic" nature of this enzyme. Additionally, a search for genes probably involved in sulfur metabolism in the genome sequence of Sb. thermosulfidooxidans DSM 9293(T) was done. Interestingly, no sox genes were found. Two sor genes, a complete heterodisulfidereductase (hdr) gene cluster, three tetrathionate hydrolase (tth) genes, three sulfide quinonereductase (sqr), as well as the doxD component of a thiosulfate quinonereductase (tqo) were found. Seven At. caldus strains were tested for Sor activity, which was not detected in any of them. We provide evidence that an earlier reported Sor activity from At. caldus S1 and S2 strains most likely was due to the presence of a Sulfobacillus contaminant. PMID- 27682114 TI - Dynamic In Vitro Models of the Human Gastrointestinal Tract as Relevant Tools to Assess the Survival of Probiotic Strains and Their Interactions with Gut Microbiota. AB - The beneficial effects of probiotics are conditioned by their survival during passage through the human gastrointestinal tract and their ability to favorably influence gut microbiota. The main objective of this study was to use dynamic in vitro models of the human digestive tract to investigate the effect of fasted or fed state on the survival kinetics of the new probiotic Saccharomyces cerevisiae strain CNCM I-3856 and to assess its influence on intestinal microbiota composition and activity. The probiotic yeast showed a high survival rate in the upper gastrointestinal tract whatever the route of admistration, i.e., within a glass of water or a Western-type meal. S. cerevisiae CNCM I-3856 was more sensitive to colonic conditions, as the strain was not able to colonize within the bioreactor despite a twice daily administration. The main bacterial populations of the gut microbiota, as well as the production of short chain fatty acids were not influenced by the probiotic treatment. However, the effect of the probiotic on the gut microbiota was found to be individual dependent. This study shows that dynamic in vitro models can be advantageously used to provide useful insight into the behavior of probiotic strains in the human digestive environment. PMID- 27682115 TI - Carbon-Starvation Induces Cross-Resistance to Thermal, Acid, and Oxidative Stress in Serratia marcescens. AB - The broad host-range pathogen Serratia marcescens survives in diverse host and non-host environments, often enduring conditions in which the concentration of essential nutrients is growth-limiting. In such environments, carbon and energy source starvation (carbon-starvation) is one of the most common forms of stress encountered by S. marcescens. Related members of the family Enterobacteriaceae are known to undergo substantial changes in gene expression and physiology in response to the specific stress of carbon-starvation, enabling non-spore-forming cells to survive periods of prolonged starvation and exposure to other forms of stress (i.e., starvation-induced cross-resistance). To determine if carbon starvation also results in elevated levels of cross-resistance in S. marcescens, both log-phase and carbon-starved cultures, depleted of glucose before the onset of high cell-density stationary-phase, were grown in minimal media at either 30 degrees C or 37 degrees C and were then challenged for resistance to high temperature (50 degrees C), low pH (pH 2.8), and oxidative stress (15 mM H2O2). In general, carbon-starved cells exhibited a higher level of resistance to thermal stress, acid stress, and oxidative stress compared to log-phase cells. The extent of carbon-starvation-induced cross-resistance was dependent on incubation temperature and on the particular strain of S. marcescens. In addition, strain- and temperature-dependent variations in long-term starvation survival were also observed. The enhanced stress-resistance of starved S. marcescens cells could be an important factor in their survival and persistence in many non-host environments and within certain host microenvironments where the availability of carbon sources is suboptimal for growth. PMID- 27682118 TI - Movement of Salmonella serovar Typhimurium and E. coli O157:H7 to Ripe Tomato Fruit Following Various Routes of Contamination. AB - Salmonella serovars have been associated with the majority of foodborne illness outbreaks involving tomatoes, and E. coli O157:H7 has caused outbreaks involving other fresh produce. Contamination by both pathogens has been thought to originate from all points of the growing and distribution process. To determine if Salmonella serovar Typhimurium and E. coli O157:H7 could move to the mature tomato fruit of different tomato cultivars following contamination, three different contamination scenarios (seed, leaf, and soil) were examined. Following contamination, each cultivar appeared to respond differently to the presence of the pathogens, with most producing few fruit and having overall poor health. The Micro-Tom cultivar, however, produced relatively more fruit and E. coli O157:H7 was detected in the ripe tomatoes for both the seed- and leaf- contaminated plants, but not following soil contamination. The Roma cultivar produced fewer fruit, but was the only cultivar in which E. coli O157:H7 was detected via all three routes of contamination. Only two of the five cultivars produced tomatoes following seed-, leaf-, and soil- contamination with Salmonella Typhimurium, and no Salmonella was found in any of the tomatoes. Together these results show that different tomato cultivars respond differently to the presence of a human pathogen, and for E. coli O157:H7, in particular, tomato plants that are either contaminated as seeds or have a natural opening or a wound, that allows bacteria to enter the leaves can result in plants that have the potential to produce tomatoes that harbor internalized pathogenic bacteria. PMID- 27682117 TI - Thermus thermophilus as a Source of Thermostable Lipolytic Enzymes. AB - Lipolytic enzymes, esterases (EC 3.1.1.1) and lipases (EC 3.1.1.3), catalyze the hydrolysis of ester bonds between alcohols and carboxylic acids, and its formation in organic media. At present, they represent about 20% of commercialized enzymes for industrial use. Lipolytic enzymes from thermophilic microorganisms are preferred for industrial use to their mesophilic counterparts, mainly due to higher thermostability and resistance to several denaturing agents. However, the production at an industrial scale from the native organisms is technically complicated and expensive. The thermophilic bacterium Thermus thermophilus (T. thermophilus) has high levels of lipolytic activity, and its whole genome has been sequenced. One esterase from the T. thermophilus strain HB27 has been widely characterized, both in its native form and in recombinant forms, being expressed in mesophilic microorganisms. Other putative lipases/esterases annotated in the T. thermophilus genome have been explored and will also be reviewed in this paper. PMID- 27682119 TI - The Effect of Tellurite on Highly Resistant Freshwater Aerobic Anoxygenic Phototrophs and Their Strategies for Reduction. AB - Six fresh water aerobic anoxygenic phototrophs (Erythromicrobium ezovicum, strain E1; Erythromicrobium hydrolyticum, E4(1); Erythromicrobium ramosum, E5; Erythromonas ursincola, KR99; Sandaracinobacter sibiricus, RB 16-17; and Roseococcus thiosulfatophilus, RB3) possessing high level resistance to TeO3(2-) and the ability to reduce it to elemental Te were studied to understand their interaction with this highly toxic oxyanion. Tested organic carbon sources, pH, and level of aeration all had an impact on reduction. Physiological and metabolic responses of cells to tellurite varied among strains. In its presence, versus absence, cellular biomass either increased (KR99, 66.6% and E5, 21.2%) or decreased (RB3, 66.1%, E1, 57.8%, RB 16-17, 41.5%, and E4(1), 21.3%). The increase suggests a possible benefit from tellurite. Cellular ATP production was similarly affected, resulting in an increase (KR99, 15.2% and E5, 38.9%) or decrease (E4(1), 31.9%; RB 16-17, 48.8%; RB3, 55.9%; E1, 35.9%). Two distinct strategies to tellurite reduction were identified. The first, found in E4(1), requires de novo protein preparations as well as an undisturbed whole cell. The second strategy, in which reduction depended on a membrane associated constitutive reductase, was used by the remaining strains. PMID- 27682116 TI - Gut Microbiota and Host Reaction in Liver Diseases. AB - Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases. PMID- 27682120 TI - The Potential of the Yeast Debaryomyces hansenii H525 to Degrade Biogenic Amines in Food. AB - Twenty-six yeasts from different genera were investigated for their ability to metabolize biogenic amines. About half of the yeast strains produced one or more different biogenic amines, but some strains of Debaryomyces hansenii and Yarrowia lipolytica were also able to degrade such compounds. The most effective strain D. hanseniii H525 metabolized a broad spectrum of biogenic amines by growing and resting cells. Degradation of biogenic amines by this yeast isolate could be attributed to a peroxisomal amine oxidase activity. Strain H525 may be useful as a starter culture to reduce biogenic amines in fermented food. PMID- 27682121 TI - Bioactivities of Ketones Terpenes: Antifungal Effect on F. verticillioides and Repellents to Control Insect Fungal Vector, S. zeamais. AB - Maize is one the most important staple foods in the world. However, numerous pests, such as fungal pathogens, e.g., Fusarium verticillioides, and insects, such as Sitophlilus zeamais, attack maize grains during storage. Many F. verticillioides strains produce fumonisins, one of the most important mycotoxin that causes toxic effects on human and animal health. This situation is aggravated by the insect fungal vector, Sitophlilus zeamais, which contributes to the dispersal of fungal spores, and through feeding damage, provide entry points for fungal infections. The aim of this study was to evaluate in vitro bioassays, the antifungal activity on F. verticillioides M3125 and repellent effects against S. zeamais of ketone terpenes. In addition, we performed Quantitative structure activity relationship (Q-SAR) studies between physico-chemical properties of ketone terpenes and the antifungal effect. Thymoquinone was the most active compound against F. verticillioides (Minimum Inhibitory Concentration, MIC: 0.87) affecting the lag phase and the growth rate showing a total inhibition of growth at concentration higher than 2 mM (p < 0.05). The Q-SAR model revealed that the antifungal activity of ketone compounds is related to the electronic descriptor, Pi energy. Thymoquinone showed a strong repellent effect (-77.8 +/- 8.5, p < 0.001) against S. zeamais. These findings make an important contribution to the search for new compounds to control two stored pests of maize. PMID- 27682123 TI - The Microbial Resource Research Infrastructure MIRRI: Strength through Coordination. AB - Microbial resources have been recognized as essential raw materials for the advancement of health and later for biotechnology, agriculture, food technology and for research in the life sciences, as their enormous abundance and diversity offer an unparalleled source of unexplored solutions. Microbial domain biological resource centres (mBRC) provide live cultures and associated data to foster and support the development of basic and applied science in countries worldwide and especially in Europe, where the density of highly advanced mBRCs is high. The not for-profit and distributed project MIRRI (Microbial Resource Research Infrastructure) aims to coordinate access to hitherto individually managed resources by developing a pan-European platform which takes the interoperability and accessibility of resources and data to a higher level. Providing a wealth of additional information and linking to datasets such as literature, environmental data, sequences and chemistry will enable researchers to select organisms suitable for their research and enable innovative solutions to be developed. The current independent policies and managed processes will be adapted by partner mBRCs to harmonize holdings, services, training, and accession policy and to share expertise. The infrastructure will improve access to enhanced quality microorganisms in an appropriate legal framework and to resource-associated data in a more interoperable way. PMID- 27682124 TI - Susceptibility of Select Agents to Predation by Predatory Bacteria. AB - Select Agents are microorganisms and toxins considered to be exploitable as biological weapons. Although infections by many Select Agents can be treated by conventional antibiotics, the risk of an emerging or engineered drug resistant strain is of great concern. One group of microorganisms that is showing potential to control drug resistant Gram-negative bacteria are the predatory bacteria from the genera Bdellovibrio spp. and Micavibrio spp. In this study, we have examined the ability of Bdellovibrio bacteriovorus (B. bacteriovorus) strain 109J, HD100 and Micavibrio aeruginosavorus (M. aeruginosavorus) ARL-13 to prey on a variety of Select Agents. Our findings demonstrate that B. bacteriovorus and M. aeruginosavorus are able to prey efficiently on Yersinia pestis and Burkholderia mallei. Modest predation was also measured in co-cultures of B. bacteriovorus and Francisella tularensis. However, neither of the predators showed predation when Burkholderia pseudomallei and Brucella melitensis were used as prey. PMID- 27682122 TI - Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. AB - Hydrogen sulfide (H2S) is a Janus-faced molecule. On one hand, several toxic functions have been attributed to H2S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H2S delivery based clinical therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H2S has been found to have pleiotropic effects on physiology and health. H2S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addition to H2S production by mammalian cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), H2S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate reduction (DSR) pathway. In the gut, H2S regulates functions such as inflammation, ischemia/ reperfusion injury and motility. H2S derived from gut microbes has been found to be associated with gastrointestinal disorders such as ulcerative colitis, Crohn's disease and irritable bowel syndrome. This underscores the importance of gut microbes and their production of H2S on host physiology and pathophysiology. PMID- 27682126 TI - Assessment of Carbapenem Resistance in Enterobacteriaceae with the Rapid and Easy to-Use Chromogenic beta Carba Test. PMID- 27682125 TI - Metabolic Interactions in the Gastrointestinal Tract (GIT): Host, Commensal, Probiotics, and Bacteriophage Influences. AB - Life on this planet has been intricately associated with bacterial activity at all levels of evolution and bacteria represent the earliest form of autonomous existence. Plants such as those from the Leguminosae family that form root nodules while harboring nitrogen-fixing soil bacteria are a primordial example of symbiotic existence. Similarly, cooperative activities between bacteria and animals can also be observed in multiple domains, including the most inhospitable geographical regions of the planet such as Antarctica and the Lower Geyser Basin of Yellowstone National Park. In humans bacteria are often classified as either beneficial or pathogenic and in this regard we posit that this artificial nomenclature is overly simplistic and as such almost misinterprets the complex activities and inter-relationships that bacteria have with the environment as well as the human host and the plethora of biochemical activities that continue to be identified. We further suggest that in humans there are neither pathogenic nor beneficial bacteria, just bacteria embraced by those that tolerate the host and those that do not. The densest and most complex association exists in the human gastrointestinal tract, followed by the oral cavity, respiratory tract, and skin, where bacteria-pre- and post-birth-instruct the human cell in the fundamental language of molecular biology that normally leads to immunological tolerance over a lifetime. The overall effect of this complex output is the elaboration of a beneficial milieu, an environment that is of equal or greater importance than the bacterium in maintaining homeostasis. PMID- 27682127 TI - Accuracy of Automated Flow Cytometry-Based Leukocyte Counts To Rule Out Urinary Tract Infection in Febrile Children: a Prospective Cross-Sectional Study. AB - Automated flow cytometry of urine remains an incompletely validated method to rule out urinary tract infection (UTI) in children. This cross-sectional analytical study was performed to compare the predictive values of flow cytometry and a dipstick test as initial diagnostic tests for UTI in febrile children and prospectively included 1,106 children (1,247 episodes). Urine culture was used as the gold standard test for diagnosing UTI. The performance of screening tests to diagnose UTI were established using receiver operating characteristic (ROC) analysis. Among these 1,247 febrile episodes, 221 UTIs were diagnosed (17.7% [95% confidence interval {CI}, 15.6 to 19.8%]). The area under the ROC curve for flow cytometry white blood cell (WBC) counts (0.99 [95% CI, 0.98 to 0.99]) was significantly superior to that for red blood cell (0.74 [95% CI, 0.70 to 0.78]) and bacterial counts (0.89 [95% CI, 0.87 to 0.92]) (P < 0.001). Urinary WBC counts also had a significantly higher area under the ROC curve than that of the leukocyte esterase (LE) dipstick (0.92 [95% CI, 0.90 to 0.94]), nitrite dipstick (0.83 [95% CI, 0.80 to 0.87]), or the combination of positive LE and/or nitrite dipstick (0.91 [95% CI, 0.89 to 0.93]) test (P < 0.001). The presence of >=35 WBC/MUl of urine was the best cutoff point, yielding both a high sensitivity (99.5% [95% CI, 99 to 100%]) and an acceptable specificity (80.6% [95% CI, 78 to 83%]). Using this cutoff point would have reduced the number of samples sent to the laboratory for culture by 67%. In conclusion, the determination of urinary WBC counts by flow cytometry provides optimal performance as an initial diagnostic test for UTI in febrile children. PMID- 27682128 TI - Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis. AB - Current migratory movements require new strategies for rapidly tracking the transmission of high-risk imported Mycobacterium tuberculosis strains. Whole genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design PCRs to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally at separate institutions. In this study, we describe the urgent implementation of a system that integrates genomics and molecular tools in a genuine high-risk epidemiological alert involving 2 independent importations of extensively drug resistant (XDR) and pre-XDR Beijing M. tuberculosis strains from Russia into Spain. Both cases involved commercial sex workers with long-standing tuberculosis (TB). The system was based on strain-specific PCRs tailored from WGS data that were transferred to the local node that was managing the epidemiological alert. The optimized tests were available for prospective implementation in the local node 33 working days after receiving the primary cultures of the XDR strains and were applied to all 42 new incident cases. An interpretable result was obtained in each case (directly from sputum for 27 stain positive cases) and corresponded to the amplification profiles for strains other than the targeted pre-XDR and XDR strains, which made it possible to prospectively rule out transmission of these high-risk strains at diagnosis. PMID- 27682129 TI - Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Mycobacterium abscessus Subspecies According to Whole-Genome Sequencing. AB - This study was undertaken to evaluate the utility of matrix-assisted laser desorption ionization-time of flight mass spectrometry with the Vitek MS Plus system for identifying Mycobacterium abscessus subspecies in order to facilitate more rapid and appropriate therapy. A total of 175 clinical M. abscessus strains were identified by whole-genome sequencing analysis: 139 Mycobacterium abscessus subsp. abscessus and 36 Mycobacterium abscessus subsp. massiliense The research use-only (RUO) Saramis Knowledge Base database v.4.12 was modified accordingly by adding 40 M. abscessus subsp. abscessus and 19 M. abscessus subsp. massiliense reference spectra to construct subspecies SuperSpectra. A blind test, used to validate the remaining 116 isolates, yielded 99.1% (n = 115) reliability and only 0.9% (n = 1) error for subspecies identification. Among the two subspecies SuperSpectra, two specific peaks were found for M. abscessus subsp. abscessus and four specific peaks were found for M. abscessus subsp. massiliense Our study is the first to report differential peaks 3,354.4 m/z and 6,711.1 m/z, which were specific for M. abscessus subsp. massiliense Our research demonstrates the capacity of the Vitek MS RUO Saramis Knowledge Base database to identify M. abscessus at the subspecies level. Moreover, it validates the potential ease and accuracy with which it can be incorporated into the IVD system for the identification of M. abscessus subspecies. PMID- 27682130 TI - Use of a Molecular Panel To Aid in Diagnosis of Culture-Negative Meningitis. PMID- 27682132 TI - Do patient characteristics impact the relationship between anatomic prolapse and vaginal bulge symptoms? AB - INTRODUCTION AND HYPOTHESIS: Seeing or feeling a vaginal bulge is the most specific symptom for identifying prolapse. Bulge symptoms are becoming increasingly important as a surgical outcome measure. Our objectives were to identify patient characteristics associated with the symptom of a vaginal bulge and to determine whether those characteristics impact the relationship between symptoms and anatomic prolapse. METHODS: A cross-sectional analysis of new urogynecology patients was performed. Standardized history and examination forms were used. Patient characteristics associated with vaginal bulge at p <=0.10 were entered in logistic regression models. Interactions between patient characteristics and prolapse were tested to determine whether patient factors modified the association between anatomic prolapse and symptoms. RESULTS: We evaluated 685 patients with mean age of 58.5 years. Patients reporting a vaginal bulge were slightly older, more likely postmenopausal, and had greater parity and body mass index (BMI). They were more likely to report prior prolapse surgery (p <0.05) and more often previously underwent hysterectomy (p = 0.10). In multivariable analysis, prolapse, age group, and vaginal parity were associated with the bulge symptom. Receiver operating characteristic (ROC) area under the curve (AUC) was 0.87 [95 % confidence interval (CI) 0.84-0.90], suggesting good predictive value of maximum vaginal descent for a vaginal bulge symptom. The AUC for the youngest women was lower than for middle and older age groups (p < 0.01). The optimal cutoff for defining prolapse associated with a vaginal bulge symptom was the hymen. CONCLUSIONS: Age and vaginal parity were independently associated with the vaginal bulge symptom. The level of vaginal descent did not predict a bulge symptom as accurately in younger patients. PMID- 27682133 TI - 19 F NMR matrix-assisted DOSY: a versatile tool for differentiating fluorinated species in mixtures. AB - NMR is the most versatile tool for the analysis of organic compounds and, in combination with Diffusion-Ordered Spectroscopy ('DOSY'), can give information on compounds in complex mixtures without the need for physical separation. In mixtures where the components' diffusion coefficients are nearly identical, for example because of similar sizes, Matrix-Assisted DOSY ('MAD') can help separate the signals of different constituents, resolving their spectra. Unfortunately, DOSY (including MAD) typically fails where signals overlap, as is common in 1 H NMR. Using 19 F NMR avoids such problems, because the great sensitivity of the 19 F chemical shift to local environment leads to very well-dispersed spectra. Another advantage is the absence of any 19 F background signals from the matrices typically used, avoiding interference with the analyte signals. In this study, differentiation among fluorophenol and fluoroaniline isomers was evaluated using normal and reverse micelles-of sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and dioctyl sodium sulfosuccinate (AOT)-as matrices. These surfactants provide useful diffusion separation in these difficult mixtures, with all the solutes interacting with the matrices to different extents, in some cases leading to differences in diffusion coefficient of more than 30%. The best matrices for separating the signals of both acid and basic species were shown to be AOT and CTAB, which are useful over a wide range of surfactant concentration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27682131 TI - Treatment of vaginal stenosis with fasciocutaneous Singapore flap. AB - INTRODUCTION: Vaginal stenosis is an unfortunate complication that can occur after pelvic radiation therapy for gynecologic or colorectal malignancies. Treatment is challenging and can require significant reconstructive surgery. The objective of this video is to present a case of vaginal stenosis after radiation and describe vaginal reconstruction with a fasciocutaneous Singapore flap. METHODS: We describe the case of a 42-year-old woman with a history of stage 3 colorectal cancer who underwent partial colectomy, chemotherapy, and pelvic radiation. She subsequently developed a rectovaginal fistula requiring repair with a right-sided gracilis flap. When her stenosis recurred, she underwent vaginal reconstruction with a medial thigh flap. RESULTS: The Singapore flap is a pudendal thigh flap centered on the labial crural fold with a base at the perineal body. As the cutaneous innervation is spared, this flap is sensate. This technique is one option for patients with complex vaginal stenosis who have failed conservative management. However, it is imperative the patient perform vaginal dilation postoperatively and maintain close follow-up with her surgeon, as vaginal stenosis can recur. CONCLUSIONS: Postradiation vaginal stenosis is a complex condition to treat; however, vaginal reconstruction with a thigh flap can provide excellent cosmetic and functional results. PMID- 27682135 TI - Postmenopausal osteoporosis. PMID- 27682136 TI - Effect of Conjugated Linoleic Acid-enriched Butter After 24 hours of Intestinal Mucositis Induction. AB - Mucositis is the most common side effect due to chemotherapy or radiotherapy. It refers to the inflammation of intestinal mucous membranes, and it is associated with complications such as diarrhea, weight loss, and increased intestinal permeability (IP). This study was designed to evaluate the effect of diet containing conjugated linoleic acid (CLA)-enriched butter on intestinal damage and inflammatory response after 24 h of 5-fluorouracil (5-FU)-induced mucositis. Mice were divided into four groups: CTL; CLA; 5-FU, and CLA 5-FU, and they were fed for 31 days. On the 30th experimental day, mucositis was induced by unique injection of 300 mg/kg of 5-FU. After 24 h (31st experimental day), IP was evaluated; ileum and fecal material were collected to determine cytokine level and myeloperoxidase (MPO) activity and secretory immunoglobulin A (sIgA). The 5 FU group showed an increase in IP and MPO activity (CTL vs. 5-FU: P < 0.05). Additionally, increased levels of IP and MPO were observed in CLA 5-FU group compared to those in the test groups (P < 0.05). Animals in the CLA 5-FU group showed reduced concentrations of sIgA (CTL vs. CLA 5-FU: P < 0.05). CLA-enriched butter exacerbating the 5-FU-induced intestinal damage. Safety concerns regarding the use of CLA require further investigation. PMID- 27682137 TI - Short-term effects of meteorological factors on pediatric hand, foot, and mouth disease in Guangdong, China: a multi-city time-series analysis. AB - BACKGROUND: Literature shows inconsistency in meteorological effects on Hand, foot, and mouth disease (HFMD) in different cities. This multi-city study aims to investigate the meteorological effects on pediatric HFMD occurrences and the potential effect modification by geographic factors. METHODS: Based on daily time series data in eight major cities in Guangdong, China during 2009-2013, mixed generalized additive models were employed to estimate city-specific meteorological effects on pediatric HFMD. Then, a random-effect multivariate meta analysis was conducted to obtain the pooled risks and to explore heterogeneity explained by city-level factors. RESULTS: There were a total of 400,408 pediatric HFMD cases (children aged 0-14 years old) with an annual incidence rate of 16.6 cases per 1,000 children, clustered in males and children under 3 years old. Daily average temperature was positively associated with pediatric HFMD cases with the highest pooled relative risk (RR) of 1.52 (95 % CI: 1.30-1.77) at the 95th percentile of temperature (30.5 degrees C) as compared to the median temperature (23.5 degrees C). Significant non-linear positive effects of high relative humidity were also observed with a 13 % increase (RR = 1.13, 95 % CI: 1.00-1.28) in the risk of HFMD at the 99th percentile of relative humidity (86.9 %) as compared to the median value (78 %). The effect estimates showed geographic variations among the cities which was significantly associated with city's latitude and longitude with an explained heterogeneity of 32 %. CONCLUSIONS: Daily average temperature and relative humidity had non-linear and delayed effects on pediatric HFMD and the effects varied across different cities. These findings provide important evidence for comprehensive understanding of the climatic effects on pediatric HFMD and for the authority to take targeted interventions and measures to control the occurrence and transmission of HFMD. PMID- 27682134 TI - Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer. AB - INTRODUCTION: A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. MATERIALS AND METHODS: We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians. Comparison with prior molecular testing results, when available, was performed to assess concordance. RESULTS: We identified a RAS/RAF pathway mutation or amplification in 62% of cases, including samples harboring KRAS mutations outside of the codon 12/13 hotspot region in 6.4% of cases. Among cases with KRAS non-codon 12/13 alterations for which prior test results were available, 79 of 90 (88%) were not identified by focused testing. Of 1,644 RAS/RAF wild-type cases analyzed by CGP, 31% harbored a genomic alteration (GA) associated with resistance to anti-EGFR therapy in advanced CRC including mutations in PIK3CA, PTEN, EGFR, and ERBB2. We also identified other targetable GA, including novel kinase fusions, receptor tyrosine kinase amplification, activating point mutations, as well as microsatellite instability. CONCLUSION: Extended genomic profiling reliably detects alterations associated with lack of benefit to anti-EGFR therapy in advanced CRC, while simultaneously identifying alterations potentially important in guiding treatment. The use of CGP during the course of clinical care allows for the refined selection of appropriate targeted therapies and clinical trials, increasing the chance of clinical benefit and avoiding therapeutic futility. IMPLICATIONS FOR PRACTICE: Comprehensive genomic profiling (CGP) detects diverse genomic alterations associated with lack of benefit to anti-epidermal growth factor receptor therapy in advanced colorectal cancer (CRC), as well as targetable alterations in many other genes. This includes detection of a broad spectrum of activating KRAS alterations frequently missed by focused molecular hotspot testing, as well as other RAS/RAF pathway alterations, mutations shown to disrupt antibody binding, RTK activating point mutations, amplifications, and rearrangements, and activating alterations in downstream effectors including PI3K and MEK1. The use of CGP in clinical practice is critical to guide appropriate selection of targeted therapies for patients with advanced CRC. PMID- 27682139 TI - How many children and young people with life-limiting conditions are clinically unstable? A national data linkage study. AB - OBJECTIVE: To determine the clinical stage (stable, unstable, deteriorating or dying) for children and young people (CYP) aged 0-25 years in Scotland with life limiting conditions (LLCs). DESIGN: National cohort of CYP with LLCs using linked routinely collected healthcare data. SETTING: Scotland. PATIENTS: 20 436 CYP identified as having LLCs and resident in Scotland between 1 April 2009 and 31 March 2014. MAIN OUTCOME: Clinical stage based on emergency inpatient and intensive care unit admissions and date of death. RESULTS: Over 2200 CYP with LLCs in Scotland were unstable, deteriorating or dying in each year. Compared with 1-year-olds to 5-year-olds, children under 1 year of age had the highest risk of instability (OR 6.4, 95% CI 5.7 to 7.1); all older age groups had lower risk. Girls were more likely to be unstable than boys (OR 1.15, 95% CI 1.06 to 1.24). CYP of South Asian (OR 1.61, 95% CI 1.28 to 2.01), Black (OR 1.58, 95% CI 1.04 to 2.41) and Other (OR 1.33, 95% CI 1.02 to 1.74) ethnicity were more likely to experience instability than White CYP. Deprivation was not a significant predictor of instability. Compared with congenital abnormalities, CYP with most other primary diagnoses had a higher risk of instability; only CYP with a primary perinatal diagnosis had significantly lower risk (OR 0.23, 95% CI 0.19 to 0.29). CONCLUSIONS: The large number of CYP with LLCs who are unstable, deteriorating or dying may benefit from input from specialist paediatric palliative care. The age group under 1 and CYP of South Asian, Black and Other ethnicities should be priority groups. PMID- 27682138 TI - Rapid Electron Transfer within the III-IV Supercomplex in Corynebacterium glutamicum. AB - Complex III in C. glutamicum has an unusual di-heme cyt. c1 and it co-purifies with complex IV in a supercomplex. Here, we investigated the kinetics of electron transfer within this supercomplex and in the cyt. aa3 alone (cyt. bc1 was removed genetically). In the reaction of the reduced cyt. aa3 with O2, we identified the same sequence of events as with other A-type oxidases. However, even though this reaction is associated with proton uptake, no pH dependence was observed in the kinetics. For the cyt. bc1-cyt. aa3 supercomplex, we observed that electrons from the c-hemes were transferred to CuA with time constants 0.1-1 ms. The b-hemes were oxidized with a time constant of 6.5 ms, indicating that this electron transfer is rate-limiting for the overall quinol oxidation/O2 reduction activity (~210 e-/s). Furthermore, electron transfer from externally added cyt. c to cyt. aa3 was significantly faster upon removal of cyt. bc1 from the supercomplex, suggesting that one of the c-hemes occupies a position near CuA. In conclusion, isolation of the III-IV-supercomplex allowed us to investigate the kinetics of electron transfer from the b-hemes, via the di-heme cyt. c1 and heme a to the heme a3-CuB catalytic site of cyt. aa3. PMID- 27682140 TI - Therapeutic efficacy and safety of ACE inhibitors in the hypertensive paediatric population: a review. AB - PURPOSE: Since 1997, strong incentives have been introduced worldwide to improve access to safe and effective medicines addressing the therapeutic needs of children. ACE inhibitors, the most prescribed antihypertensive drugs in the paediatric population, are one of the prototype drugs targeted by the legislation initiatives. Our purpose in assembling this review is to evaluate and describe the current evidence for the efficacy and safety profile of ACE inhibitors in the paediatric population. METHODS: The authors made a descriptive review of the literature from 1980 to 2015 using the following search terms: hypertension, child, paediatric, ACE (inhibitors), renin-angiotensin aldosterone system, captopril, lisinopril, enalapril, ramipril and fosinopril. RESULTS: A total of 16 studies evaluating efficacy and safety of ACE inhibitors were included in this review. The included studies demonstrate that ACE inhibitors have the potency to decrease the systolic and/or diastolic blood pressure with an overall favourable safety profile in a short-term period. More importantly, the incentives resulted in an improvement of the overall availability of paediatric labelling, dosing and safety information for ACE inhibitors. However, they failed to fulfil several of paediatric needs: absence of long-term safety data on growth and maturation, absence of commercially available child-friendly formulations and incomplete evaluation of the entire paediatric hypertension population. CONCLUSION: Additional efforts are needed to close the gap between the availability of drugs that are labelled and indicated for paediatric use and the actual drug usage in children, especially in young children, neonates and children with severe hypertension, renal transplantation or severe renal impairment. PMID- 27682142 TI - Introduction to "Interviewing Eddie". PMID- 27682141 TI - KAP Surveys and Dengue Control in Colombia: Disentangling the Effect of Sociodemographic Factors Using Multiple Correspondence Analysis. AB - During the last few decades, several studies have analyzed and described knowledge, attitudes, and practices (KAP) of populations regarding dengue. However, few studies have applied geometric data analytic techniques to generate indices from KAP domains. Results of such analyses have not been used to determine the potential effects of sociodemographic variables on the levels of KAP. The objective was to determine the sociodemographic factors related to different levels of KAP regarding dengue in two hyper-endemic cities of Colombia, using a multiple correspondence analysis (MCA) technique. In the context of a cluster randomized trial, 3,998 households were surveyed in Arauca and Armenia between 2012 and 2013. To generate KAP indexes, we performed a MCA followed by a hierarchical cluster analysis to classify each score in different groups. A quantile regression for each of the score groups was conducted. KAP indexes explained 56.1%, 79.7%, and 83.2% of the variance, with means of 4.2, 1.4, and 3.2 and values that ranged from 1 to 7, 7 and 11, respectively. The highest values of the index denoted higher levels of knowledge and practices. The attitudes index did not show the same relationship and was excluded from the analysis. In the quantile regression, age (0.06; IC: 0.03, 0.09), years of education (0.14; IC: 0.06, 0.22), and history of dengue in the family (0.21; IC: 0.12, 0.31) were positively related to lower levels of knowledge regarding dengue. The effect of such factors gradually decreased or disappeared when knowledge was higher. The practices indexes did not evidence a correlation with sociodemographic variables. These results suggest that the transformation of categorical variables into a single index by the use of MCA is possible when analyzing knowledge and practices regarding dengue from KAP questionnaires. Additionally, the magnitude of the effect of socioeconomic variables on the knowledge scores varies according to the levels of knowledge, suggesting that other factors might be influencing higher levels of knowledge. PMID- 27682143 TI - Commentary on "Interviewing Eddie". PMID- 27682144 TI - Introduction. PMID- 27682145 TI - Pre-Implantation Genetic Screening Techniques: Implications for Clinical Prenatal Diagnosis. AB - Chromosomal aneuploidy is responsible for a significant proportion of pregnancy failures, whether conceived naturally or through in vitro fertilization (IVF). In an effort to improve the success rate of IVF, screening embryos for aneuploidy - or pre-implantation genetic screening (PGS) - has been proposed as a means of ensuring only euploid embryos are selected for transfer. Early PGS approaches were based on fluorescence in situ hybridization testing, and have been shown not to improve live birth rates. Recent developments in genetic testing technologies such as next-generation sequencing and quantitative polymerase chain reaction, coupled with embryo biopsy at the blastocyst stage - have shown promise in improving IVF outcomes, but they remain to be validated in adequately powered, prospective randomized trials. The extent to which IVF with PGS lowers the a priori risk of aneuploidy in ongoing pregnancies so conceived has been poorly described, rendering it difficult to incorporate the potential benefit of PGS into existing prenatal aneuploidy screening regimens such as cell-free DNA testing or conventional combined nuchal translucency and maternal biochemistry assessment. Further data on the sensitivity and specificity of various forms of molecular PGS testing would improve our understanding of the effectiveness and accuracy of these technologies. This, in addition to further research into methods of risk combination and assessment, would allow us to help our patients make better- informed decisions about whether or not to proceed with invasive diagnostic tests. PMID- 27682146 TI - A psychometric evaluation of the Gender Bias in Medical Education Scale. AB - BACKGROUND: Gender bias within medical education is gaining increasing attention. However, valid and reliable measures are needed to adequately address and monitor this issue. This research conducts a psychometric evaluation of a short multidimensional scale that assesses medical students' awareness of gender bias, beliefs that gender bias should be addressed, and experience of gender bias during medical education. METHODS: Using students from the University of Wollongong, one pilot study and two empirical studies were conducted. The pilot study was used to scope the domain space (n = 28). This initial measure was extended to develop the Gender Bias in Medical Education Scale (GBMES). For Study 1 (n = 172), confirmatory factor analysis assessed the construct validity of the three-factor structure (awareness, beliefs, experience) and enabled deletion of redundant items. Study 2 (n = 457) tested the generalizability of the refined scale to a new sample. Combining Study 1 and 2, invariance testing for program of study and gender was explored. The relationship of the GBMES to demographic and gender politics variables was tested. The results were analyzed in R using confirmatory factor analysis and Multiple-Indicator-Multiple-Indicator-Cause models. RESULTS: After analysis of the responses from the original 16-item GBMES (Study 1), a shortened measure of ten items fitted the data well (RMSEA = .063; CFI = .965; TLI = .951; Mean R-square of items = 58.6 %; reliability: .720-.910) and was found to generalize to a new sample in Study 2 (RMSEA = .068; CFI = .952; TLI = .933; Mean R-square of items = 55.9 %; reliability: .711-.892). The GBMES was found to be invariant across studies, gender, and program of study. Female students and those who supported gender equality had greater agreement for each of the factors. Likewise, postgraduate students reported higher scores on experience of gender bias than undergraduate students. CONCLUSION: The GBMES provides a validated short multidimensional measure for use in research and policy. Given its good reliability across different target populations and its concise length, the GBMES has much potential for application in research and education to assess students' attitudes towards gender bias. PMID- 27682147 TI - Top 10 Tips for Using Advance Care Planning Codes in Palliative Medicine and Beyond. AB - Although recommended for all persons with serious illness, advance care planning (ACP) has historically been a charitable clinical service. Inadequate or unreliable provisions for reimbursement, among other barriers, have spurred a gap between the evidence demonstrating the importance of timely ACP and recognition by payers for its delivery.1 For the first time, healthcare is experiencing a dramatic shift in billing codes that support increased care management and care coordination. ACP, chronic care management, and transitional care management codes are examples of this newer recognition of the value of these types of services. ACP discussions are an integral component of comprehensive, high quality palliative care delivery. The advent of reimbursement mechanisms to recognize these services has an enormous potential to impact palliative care program sustainability and growth. In this article, we highlight 10 tips to effectively using the new ACP codes reimbursable under Medicare. The importance of documentation, proper billing, and nuances regarding coding is addressed. PMID- 27682148 TI - Gastrointestinal Transit Assessment: Role of Scintigraphy: Where Are We Now? Where Are We Going? AB - OPINION STATEMENT: The diagnostic imaging evaluation of patients with suspected esophagogastrointestinal transit disorders is changing. Anatomical methods, e.g., barium studies, endoscopy, manometry, radiopaque markers, have long been the techniques available and used for diagnosis. The one exception has been gastric emptying, where radionuclide scintigraphy has been the standard for decades. Esophageal transit scintigraphy is an old and reliable methodology but probably underutilized. The diagnostic use of small and large intestinal transit scintigraphy is increasing, in part, because of the limitations of the other methods but, most importantly, because it is truly physiologic, i.e., the transit of radiolabeled food can be imaged and quantified from the mouth to rectum. Limitations to its wider use have been the lack of standardization, general availability, and reimbursement issues. Radionuclide methods are increasingly being used to evaluate esophagogastrointestinal transit in a single study, from top to bottom. PMID- 27682149 TI - Elevated CO2 increases energetic cost and ion movement in the marine fish intestine. AB - Energetic costs associated with ion and acid-base regulation in response to ocean acidification have been predicted to decrease the energy available to fish for basic life processes. However, the low cost of ion regulation (6-15% of standard metabolic rate) and inherent variation associated with whole-animal metabolic rate measurements have made it difficult to consistently demonstrate such a cost. Here we aimed to gain resolution in assessing the energetic demand associated with acid-base regulation by examining ion movement and O2 consumption rates of isolated intestinal tissue from Gulf toadfish acclimated to control or 1900 MUatm CO2 (projected for year 2300). The active marine fish intestine absorbs ions from ingested seawater in exchange for HCO3- to maintain water balance. We demonstrate that CO2 exposure causes a 13% increase of intestinal HCO3- secretion that the animal does not appear to regulate. Isolated tissue from CO2-exposed toadfish also exhibited an 8% higher O2 consumption rate than tissue from controls. These findings show that compensation for CO2 leads to a seemingly maladaptive persistent base (HCO3-) loss that incurs an energetic expense at the tissue level. Sustained increases to baseline metabolic rate could lead to energetic reallocations away from other life processes at the whole-animal level. PMID- 27682150 TI - Cultural perceptions and clinical experiences of nursing students in Eastern Turkey. AB - AIM: This study explored Turkish nursing students' perceptions of providing care to patients culturally different from themselves. BACKGROUND: Increasing migration will increase the need for nurses to provide care across cultural groups. METHODS: Twenty one students in the second year of a 4-year nursing programme participated in 3 focus groups. Data were analysed using directed content analysis. Research questions were based on Campinha-Bacote's model. RESULTS: Three themes were identified: perceived cultural barriers, perceived cultural facilitators and identifying culturally sensitive actions. Generally, students were able to define culture but were unable to say how culture would affect nursing practice. DISCUSSION: Students were unprepared to practice in a multicultural setting. Cultural awareness is insufficient for determining how to respond to cultural differences. LIMITATIONS: The study is limited by its restriction to a single school of nursing and a single curriculum. CONCLUSIONS: The multiple, ongoing political, religious and ethnic conflicts will require nurses to provide care to patients from other cultural groups, in some instances to people identified as adversaries to the group the nurse may represent. Understanding cultural differences is insufficient to do this effectively. IMPLICATIONS FOR NURSING EDUCATION: Learning culturally competent care requires opportunities to provide, be guided through and reflect on care to individuals from different cultural groups. IMPLICATIONS FOR ORGANIZATIONAL AND PUBLIC POLICIES: Standards for culturally competent care should be adopted by all care delivery settings. Public and organizational policies openly declaring healthcare settings as cultural safe zones, and explicit organizational commitment to culturally safe care, would set clear expectations for providers and help ensure a positive patient experience. PMID- 27682151 TI - Growth and characterization of V2 O5 thin film on conductive electrode. AB - Vanadium pentoxide V2 O5 thin films were grown at room temperature on ITO coated glass substrates by electrochemical deposition. The resulting films were annealed at 300, 400 and 500 degrees C for 1 h in ambient environment. The effect of heat treatment on the films properties such as surface morphology, crystal structure, optical absorption and photoluminescence were investigated. The x-ray diffraction study showed that the films are well crystallized with temperatures. Strong reflection from plane (400) indicated the film's preferred growth orientation. The V2 O5 films are found to be highly transparent across the visible spectrum and the measured photoluminescence quenching suggested the film's potential application in OPV device fabrication. PMID- 27682152 TI - Chemical Diversity and Antimicrobial Activity of Volatile Compounds from Zanthoxylum zanthoxyloides Lam. according to Compound Classes, Plant Organs and Senegalese Sample Locations. AB - The chemical diversity of Zanthoxylum zanthoxyloides growing wild in Senegal was studied according to volatile compound classes, plant organs and sample locations. The composition of fruit essential oil was investigated using an original targeted approach based on the combination of gas chromatography (GC) and liquid chromatography (LC) both coupled with mass spectrometry (MS). The volatile composition of Z. zanthoxyloides fruits exhibited relative high amounts of hydrocarbon monoterpenes (24.3 - 55.8%) and non-terpenic oxygenated compounds (34.5 - 63.1%). The main components were (E)-beta-ocimene (12.1 - 39%), octyl acetate (11.6 - 21.8%) and decanol (9.7 - 15.4%). The GC and GC/MS profiling of fruit essential oils showed a chemical variability according to geographical locations of plant material. The LC/MS/MS analysis of fruit oils allowed the detection of seven coumarins in trace content. The chemical composition of fruit essential oils was compared with volatile fractions of leaves and barks (root and trunk) from the same plant station. Hexadecanoic acid, germacrene D and decanal were identified as the major constituents of leaves whereas the barks (root and trunk) were dominated by pellitorine (85.8% and 57%, respectively), an atypic linear compound with amide group. The fruit essential oil exhibited interesting antimicrobial activities against Staphylococcus aureus and Candida albicans, particularly the alcohol fraction of the oil. PMID- 27682154 TI - Analysis of the impact of allergy and atopy on new onset of uveitis. AB - PURPOSE: The inappropriate immune response to harmless foreign and self-antigens is a common feature of allergy, atopy and autoimmune disease. The influence of environmental factors in the initiation of autoimmunity is not well understood. It is conceivable that immune responses to allergens may also serve as a trigger of bystander immune reactions, including autoimmunity such as uveitis. Therefore, we wanted to investigate the prevalence of allergies and atopy in patients with different types of uveitis in comparison to a control cohort. METHODS: In total, 530 consecutive patients with new-onset anterior, intermediate, posterior and panuveitis were compared to a non-uveitis control cohort consisting of 1.060 consecutive new-referral patients who attended our specialized outpatient clinics for other reasons than uveitis. Allergy and atopy status as well as demographic data (age, gender and ethnicity) were obtained by standardized interviewer assisted questionnaires. RESULTS: Uveitis case cohort and control cohort did not differ significantly in the allergy status (p = 0.910), such as the history of pollen allergy (p = 0.671), history of drug allergy (p = 0.920), history of food allergy (p = 0.941), history of house dust mite allergy (p = 0.197) or history of other allergens (p = 0.593), nor in the atopy status (p = 0.802), such as the history of atopic dermatitis (p = 0.365), history of asthma (p = 0.430) or history of allergic rhinitis (p = 0.115). CONCLUSIONS: Our results argue against a substantial influence of allergies and atopy on the onset of uveitis. PMID- 27682153 TI - Clinical-Pathological Conference Series from the Medical University of Graz : Case No 160: 33-year-old woman with tetraparesis on Easter Sunday. PMID- 27682155 TI - The potential for nurses to contribute to and lead improvement science in health care. AB - AIM: A discussion of how nurses can contribute to and lead improvement science activities in health care. BACKGROUND: Quality failures in health care have led to the urgent need for healthcare quality improvement. However, commonly quality improvement interventions proceed to practice implementation without rigorous methods or sufficient empirical evidence. This lack of evidence for quality improvement has led to the development of improvement science, which embodies quality improvement research and quality improvement practice. This paper discusses how the discipline of nursing and the nursing profession possesses many strengths that enable nurses to lead and to play an integral role in improvement science activities. However, we also discuss that there are insufficiencies in nursing education that require attention for nurses to truly contribute to and lead improvement science in health care. DESIGN: Discussion paper. DATA SOURCES: This paper builds on a collection of our previous work, a 12-month scoping review (March 2013-March 2014), baseline study on a quality improvement management system (Lean), interviews with nurses on quality improvement implementation and supporting literature. IMPLICATIONS FOR NURSING: This paper highlights how nurses have the philosophical, theoretical, political and ethical positioning to contribute to and lead improvement science activities. However up to now, the potential for nurses to lead improvement science activities has not been fully used. CONCLUSION: We suggest that one starting point is to include improvement science in nursing education curricula. Specifically, there needs to be increased focus on the nursing roles and skills needed to contribute to and lead healthcare improvement science activities. PMID- 27682157 TI - Assessment of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in benign and malignant salivary gland neoplasms. AB - BACKGROUND: The role of BRAF mutations in cancerogenesis has been demonstrated in several solid tumor types. However, in salivary gland tumors, this genetic alteration is very uncommon, and its role still remains unclear. Thus, the aim of this study was to analyze BRAF V600E (VE1) protein expression with BRAF mutation status in codon 600, in malignant and benign salivary gland tumors. METHODS: Studies were performed on archived formalin-fixed paraffin-embedded tissue sections derived from 95 patients who underwent surgery for tumors of the salivary gland. Immunohistochemical staining (IHC) on tissue microarray slides was performed for evaluation of BRAF V600E (VE1) protein expression, and the automatic molecular diagnostics platform was used for the evaluation of mutations in codon 600 of BRAF gene. RESULTS: IHC cytoplasmic expression of BRAF V600E (VE1) protein was found in two of 95 cases: one case of adenocarcinoma NOS (one of three; 33%) and one case of carcinoma ex pleomorphic adenoma (one of five; 20%). Although, in IHC studies, nuclear BRAF V600E (VE1) protein expression was found in 14 (15%) of the analyzed cases: nine of 28 (32%) cases of pleomorphic adenoma, three of five (60%) cases of ductal carcinoma, one of nine (11%) case of mucoepidermoid carcinoma, and in one of five (20%) case of carcinoma ex pleomorphic adenoma. All cases were negative for polymerase chain reaction PCR based analyses of BRAF mutations in codon 600. CONCLUSIONS: In studied salivary gland cancers, no PCR-based prove mutations of BRAF V600 were detected. Further molecular analyses are necessary to rapid molecular arrays for the identification of specific mutations, optimal for individualized targeted therapies. PMID- 27682158 TI - Reduction mammoplasty using oxidized regenerated cellulose as a filler in breast conservation surgery. AB - : Oncoplastic surgery of the breast has generated great excitement over the past years and has become an integrated component of the surgical treatment of breast cancer. Oncoplastic procedures (OPP) associate the best surgical oncologic principles to achieve wide tumor-free margins with the best principles of plastic surgery to optimize cosmetic outcomes. So, a number of conventional mammoplasty techniques have been adapted to allow reconstruction of resection defects with parenchymal flaps using a variety of different approaches. Thanks to these oncoplastic techniques, the role of breast conserving surgery (BCS) has been extended to include a group of patients who would otherwise require mastectomy to achieve adeguate tumor clearance. However, even with the use of therapeutic mammoplasties, cosmetic outcomes may result unsatisfying when a large volume of parenchyma has to be removed, particularly in medium size breasts and for tumor localized in unfavourable location as central, inner-upper and lower quadrants. Recently, it has been proposed the use of oxidized regenerated cellulose (ORC) as a reconstructive biomaterial to optimize the aesthetic results after OPP. The aim of this article is to describe the standard pattern of an innovative surgical oncoplastic technique with ORC, that we have called "QUORC" (QUadrantectomy with Oxidized Regenerated Cellulose), to improve cosmetic results and minimize the possible postoperative complications after therapeutic mammaplasties. KEY WORDS: Breast cancer, Cosmetic results, Oncoplastic surgery, Oxidized regenerated cellulose, QUORC technique. PMID- 27682159 TI - Spontaneous remission of congenital AML with skin involvement and t(1;11)(p32;q23). PMID- 27682160 TI - Atrioventricular depolarization differences identify coronary artery anomalies in Kawasaki disease. AB - BACKGROUND: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. Signal average electrocardiogram changes in patients during the acute phase of KD with coronary artery anomalies (CAA) include depolarization changes. We set out to determine if 12-lead-derived atrioventricular depolarization differences can identify CAA in patients with KD. METHODS: A blinded, retrospective case-control study of patients with KD was performed. Deep Q waves, corrected QT-intervals (QTc), spatial QRS-T angles, T-wave vector magnitudes (RMS-T), and a novel parameter for assessment of atrioventricular depolarization difference (the spatial PR angle) and a two dimensional PR angle were assessed. Comparisons between groups were performed to test for significant differences. RESULTS: One hundred one patients with KD were evaluated, with 68 having CAA (67.3%, mean age 3.6 +/- 3.0 years, 82.6% male), and 32 without CAA (31.7%, mean age 2.7 +/- 3.2 years, 70.4% male). The spatial PR angle significantly discriminated KD patients with CAA from those without, 59.7 degrees +/- 31.1 degrees versus 41.6 degrees +/- 11.5 degrees (p < .001). A spatial PR angle cutoff value of 56.9 degrees gave positive/negative predictive values and odds ratios of 93.8%, 43.5%, and 11.5% (95% confidence interval (CI) 2.6 52.2). The two dimensional PR angle either below 7 degrees or above 92 degrees gave positive/negative predictive values and odds ratios of 100.0%, 38.8%, and 21.1% (95% CI 1.2-362.8). No other parameters significantly differentiated the groups. CONCLUSION: Atrioventricular depolarization differences, measured by the spatial or two dimensional PR angle differentiate KD patients with CAA versus those without. PMID- 27682156 TI - The geographical distribution and prevalence of Echinococcus multilocularis in animals in the European Union and adjacent countries: a systematic review and meta-analysis. AB - BACKGROUND: This study aimed to provide a systematic review on the geographical distribution of Echinococcus multilocularis in definitive and intermediate hosts in the European Union (EU) and adjacent countries (AC). The relative importance of the different host species in the life-cycle of this parasite was highlighted and gaps in our knowledge regarding these hosts were identified. METHODS: Six databases were searched for primary research studies published from 1900 to 2015. From a total of 2,805 identified scientific papers, 244 publications were used for meta-analyses. RESULTS: Studies in 21 countries reported the presence of E. multilocularis in red foxes, with the following pooled prevalence (PP): low (<= 1 %; Denmark, Slovenia and Sweden); medium (> 1 % to < 10 %; Austria, Belgium, Croatia, Hungary, Italy, the Netherlands, Romania and the Ukraine); and high (> 10 %; Czech Republic, Estonia, France, Germany, Latvia, Lithuania, Poland, Slovakia, Liechtenstein and Switzerland). Studies from Finland, Ireland, the United Kingdom and Norway reported the absence of E. multilocularis in red foxes. However, E. multilocularis was detected in Arctic foxes from the Arctic Archipelago of Svalbard in Norway. CONCLUSIONS: Raccoon dogs (PP 2.2 %), golden jackals (PP 4.7 %) and wolves (PP 1.4 %) showed a higher E. multilocularis PP than dogs (PP 0.3 %) and cats (PP 0.5 %). High E. multilocularis PP in raccoon dogs and golden jackals correlated with high PP in foxes. For intermediate hosts (IHs), muskrats (PP 4.2 %) and arvicolids (PP 6.0 %) showed similar E. multilocularis PP as sylvatic definitive hosts (DHs), excluding foxes. Nutrias (PP 1.0 %) and murids (PP 1.1 %) could play a role in the life-cycle of E. multilocularis in areas with medium to high PP in red foxes. In areas with low PP in foxes, no other DH was found infected with E. multilocularis. When fox E. multilocularis PP was >3 %, raccoon dogs and golden jackals could play a similar role as foxes. In areas with high E. multilocularis fox PP, the wolf emerged as a potentially important DH. Dogs and cats could be irrelevant in the life-cycle of the parasite in Europe, although dogs could be important for parasite introduction into non-endemic areas. Muskrats and arvicolids are important IHs. Swine, insectivores, murids and nutrias seem to play a minor or no role in the life-cycle of the parasite within the EU and ACs. PMID- 27682161 TI - Engineering island-chain silicon nanowires via a droplet mediated Plateau Rayleigh transformation. AB - The ability to program highly modulated morphology upon silicon nanowires (SiNWs) has been fundamental to explore new phononic and electronic functionalities. We here exploit a nanoscale locomotion of metal droplets to demonstrate a large and readily controllable morphology engineering of crystalline SiNWs, from straight ones into continuous or discrete island-chains, at temperature <350 degrees C. This has been accomplished via a tin (Sn) droplet mediated in-plane growth where amorphous Si thin film is consumed as precursor to produce crystalline SiNWs. Thanks to a significant interface-stretching effect, a periodic Plateau-Rayleigh instability oscillation can be stimulated in the liquid Sn droplet, and the temporal oscillation of the Sn droplets is translated faithfully, via the deformable liquid/solid deposition interface, into regular spatial modulation upon the SiNWs. Combined with a unique self-alignment and positioning capability, this new strategy could enable a rational design and single-run fabrication of a wide variety of nanowire-based optoelectronic devices. PMID- 27682164 TI - Role of Ceramide in Apoptosis and Development of Insulin Resistance. AB - This review presents data on the functional biochemistry of ceramide, one of the key sphingolipids with properties of a secondary messenger. Molecular mechanisms of the involvement of ceramide in apoptosis in pancreatic beta-cells and its role in the formation of insulin resistance in pathogenesis of type 2 diabetes are reviewed. One of the main predispositions for the development of insulin resistance and diabetes is obesity, which is associated with ectopic fat deposition and significant increase in intracellular concentrations of cytotoxic ceramides. A possible approach to the restoration of tissue sensitivity to insulin in type 2 diabetes based on selective reduction of the content of cytotoxic ceramides is discussed. PMID- 27682163 TI - LcMCII-1 is involved in the ROS-dependent senescence of the rudimentary leaves of Litchi chinensis. AB - KEY MESSAGE: LcMCII - 1 is a type II metacaspase. Over-expression of LcMCII- 1 in Arabidopsis promoted ROS-dependent and natural senescence. Virus-induced LcMCII- 1 silencing delayed the ROS-dependent senescence of the rudimentary leaves of Litchi chinensis . Litchi is an evergreen woody fruit tree that is widely cultivated in subtropical and tropical regions. Its floral buds are mixed with axillary or apical panicle primordia, leaf primordia and rudimentary leaves. A low spring temperature is vital for litchi production as it promotes the abscission of the rudimentary leaves, which could otherwise prevent panicle development. Hence, climate change could present additional challenges for litchi production. We previously reported that reactive oxygen species (ROS) can substitute low-temperature treatment to induce the senescence of rudimentary leaves. We have now identified from RNA-Seq data a litchi type II metacaspase gene, LcMCII-1, that is responsive to ROS. Silencing LcMCII-1 by virus-induced gene silencing delayed ROS-dependent senescence. The ectopic over-expression of LcMCII-1 in transgenic Arabidopsis promoted ROS-dependent and natural senescence. Consistently, the transient expression of LcMCII-1 in tobacco leaf by agroinfiltration resulted in leaf yellowing. Our findings demonstrate that LcMCII 1 is positively involved in the regulation of rudimentary leaf senescence in litchi and provide a new target for the future molecular breeding of new cultivars that can set fruit in warmer climates. PMID- 27682165 TI - The Road to Optogenetics: Microbial Rhodopsins. AB - Optogenetics technology (using light-sensitive microbial proteins to control animal cell physiology) is becoming increasingly popular in laboratories around the world. Among these proteins, particularly important are rhodopsins that transport ions across the membrane and are used in optogenetics to regulate membrane potential by light, mostly in neurons. Although rhodopsin ion pumps transport only one charge per captured photon, channelrhodopsins are capable of more efficient passive transport. In this review, we follow the history of channelrhodopsin discovery in flagellate algae and discuss the latest addition to the channelrhodopsin family, channels with anion, rather than cation, selectivity. PMID- 27682166 TI - Nucleolar Methyltransferase Fibrillarin: Evolution of Structure and Functions. AB - Fibrillarin is one of the most studied nucleolar proteins. Its main functions are methylation and processing of pre-rRNA. Fibrillarin is a highly conserved protein; however, in the course of evolution from archaea to eukaryotes, it acquired an additional N-terminal glycine and arginine-rich (GAR) domain. In this review, we discuss the evolution of fibrillarin structure and its relation to the functions of the protein in prokaryotes and eukaryotes. PMID- 27682167 TI - AP Endonuclease 1 as a Key Enzyme in Repair of Apurinic/Apyrimidinic Sites. AB - Human apurinic/apyrimidinic endonuclease 1 (APE1) is one of the key participants in the DNA base excision repair system. APE1 hydrolyzes DNA adjacent to the 5' end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety. APE1 exhibits 3'-phosphodiesterase, 3'-5'-exonuclease, and 3'-phosphatase activities. APE1 was also identified as a redox factor (Ref-1). In this review, data on the role of APE1 in the DNA repair process and in other metabolic processes occurring in cells are analyzed as well as the interaction of this enzyme with DNA and other proteins participating in the repair system. PMID- 27682162 TI - Map-based Cloning and Characterization of the BPH18 Gene from Wild Rice Conferring Resistance to Brown Planthopper (BPH) Insect Pest. AB - Brown planthopper (BPH) is a phloem sap-sucking insect pest of rice which causes severe yield loss. We cloned the BPH18 gene from the BPH-resistant introgression line derived from the wild rice species Oryza australiensis. Map-based cloning and complementation test revealed that the BPH18 encodes CC-NBS-NBS-LRR protein. BPH18 has two NBS domains, unlike the typical NBS-LRR proteins. The BPH18 promoter::GUS transgenic plants exhibited strong GUS expression in the vascular bundles of the leaf sheath, especially in phloem cells where the BPH attacks. The BPH18 proteins were widely localized to the endo-membranes in a cell, including the endoplasmic reticulum, Golgi apparatus, trans-Golgi network, and prevacuolar compartments, suggesting that BPH18 may recognize the BPH invasion at endo membranes in phloem cells. Whole genome sequencing of the near-isogenic lines (NILs), NIL-BPH18 and NIL-BPH26, revealed that BPH18 located at the same locus of BPH26. However, these two genes have remarkable sequence differences and the independent NILs showed differential BPH resistance with different expression patterns of plant defense-related genes, indicating that BPH18 and BPH26 are functionally different alleles. These findings would facilitate elucidation of the molecular mechanism of BPH resistance and the identified novel alleles to fast track breeding BPH resistant rice cultivars. PMID- 27682168 TI - 35S Promoter Methylation in Kanamycin-Resistant Kalanchoe (Kalanchoe pinnata L.) Plants Expressing the Antimicrobial Peptide Cecropin P1 Transgene. AB - Transgenic kalanchoe plants (Kalanchoe pinnata L.) expressing the antimicrobial peptide cecropin P1 gene (cecP1) under the control of the 35S cauliflower mosaic virus 35S RNA promoter and the selective neomycin phosphotransferase II (nptII) gene under the control of the nopaline synthase gene promoter were studied. The 35S promoter methylation and the cecropin P1 biosynthesis levels were compared in plants growing on media with and without kanamycin. The low level of active 35S promoter methylation further decreases upon cultivation on kanamycin-containing medium, while cecropin P1 synthesis increases. PMID- 27682169 TI - Molecular Genetic Markers of Intra- and Interspecific Divergence within Starfish and Sea Urchins (Echinodermata). AB - A fragment of the mitochondrial COI gene from isolates of several echinoderm species was sequenced. The isolates were from three species of starfish from the Asteriidae family (Asterias amurensis and Aphelasterias japonica collected in the Sea of Japan and Asterias rubens collected in the White Sea) and from the sea urchin Echinocardium cordatum (family Loveniidae) collected in the Sea of Japan. Additionally, regions including internal transcribed spacers and 5.8S rRNA (ITS1 5.8S rDNA - ITS2) were sequenced for the three studied starfish species. Phylogenetic analysis of the obtained COI sequences together with earlier determined homologous COI sequences from Ast. forbesii, Ast. rubens, and Echinocardium laevigaster from the North Atlantic and E. cordatum from the Yellow and North Seas (GenBank) placed them into strictly conspecific clusters with high bootstrap support (99% in all cases). Only two exceptions - Ast. rubens DQ077915 sequence placed with the Ast. forbesii cluster and Aph. japonica DQ992560 sequence placed with the Ast. amurensis cluster - were likely results of species misidentification. The intraspecific polymorphism for the COI gene within the Asteriidae family varied within a range of 0.2-0.9% as estimated from the genetic distances. The corresponding intrageneric and intergeneric values were 10.4-12.1 and 21.8-29.8%, respectively. The interspecific divergence for the COI gene in the sea urchin of Echinocardium genus (family Loveniidae) was significantly higher (17.1-17.7%) than in the starfish, while intergeneric divergence (14.6 25.7%) was similar to that in asteroids. The interspecific genetic distances for the nuclear transcribed sequences (ITS1 - 5.8S rDNA - ITS2) within the Asteriidae family were lower (3.1-4.5%), and the intergeneric distances were significantly higher (32.8-35.0%), compared to the corresponding distances for the COI gene. These results suggest that the investigated molecular-genetic markers could be used for segregation and identification of echinoderm species. PMID- 27682170 TI - Plastid Genome of Seseli montanum: Complete Sequence and Comparison with Plastomes of Other Members of the Apiaceae Family. AB - This work reports the complete plastid (pt) DNA sequence of Seseli montanum L. of the Apiaceae family, determined using next-generation sequencing technology. The complete genome sequence has been deposited in GenBank with accession No. KM035851. The S. montanum plastome is 147,823 bp in length. The plastid genome has a typical structure for angiosperms and contains a large single-copy region (LSC) of 92,620 bp and a small single-copy region (SSC) of 17,481 bp separated by a pair of 18,861 bp inverted repeats (IRa and IRb). The composition, gene order, and AT-content in the S. montanum plastome are similar to that of a typical flowering plant pt DNA. One hundred fourteen unique genes have been identified, including 30 tRNA genes, four rRNA genes, and 80 protein genes. Of 18 intron containing genes found, 16 genes have one intron, and two genes (ycf3, clpP) have two introns. Comparative analysis of Apiaceae plastomes reveals in the S. montanum plastome a LSC/IRb junction shift, so that the part of the ycf2 (4980 bp) gene is located in the LSC, but the other part of ycf2 (1301 bp) is within the inverted repeat. Thus, structural rearrangements in the plastid genome of S. montanum result in an enlargement of the LSC region by means of capture of a large part of ycf2, in contrast to eight Apiaceae plastomes where the complete ycf2 gene sequence is located in the inverted repeat. PMID- 27682171 TI - Dioxygenases of Chlorobiphenyl-Degrading Species Rhodococcus wratislaviensis G10 and Chlorophenol-Degrading Species Rhodococcus opacus 1CP Induced in Benzoate Grown Cells and Genes Potentially Involved in These Processes. AB - Dioxygenases induced during benzoate degradation by the actinobacterium Rhodococcus wratislaviensis G10 strain degrading haloaromatic compounds were studied. Rhodococcus wratislaviensis G10 completely degraded 2 g/liter benzoate during 30 h and 10 g/liter during 200 h. Washed cells grown on benzoate retained respiration activity for more than 90 days, and a high activity of benzoate dioxygenase was recorded for 10 days. Compared to the enzyme activities with benzoate, the activity of benzoate dioxygenases was 10-30% with 13 of 35 substituted benzoate analogs. Two dioxygenases capable of cleaving the aromatic ring were isolated and characterized: protocatechuate 3,4-dioxygenase and catechol 1,2-dioxygenase. Catechol inhibited the activity of protocatechuate 3,4 dioxygenase. Protocatechuate did not affect the activity of catechol 1,2 dioxygenase. A high degree of identity was shown by MALDI-TOF mass spectrometry for protein peaks of the R. wratislaviensis G10 and Rhodococcus opacus 1CP cells grown on benzoate or LB. DNA from the R. wratislaviensis G10 strain was specifically amplified using specific primers to variable regions of genes coding alpha- and beta-subunits of protocatechuate 3,4-dioxygenase and to two genes of the R. opacus 1CP coding catechol 1,2-dioxygenase. The products were 99% identical with the corresponding regions of the R. opacus 1CP genes. This high identity (99%) between the genes coding degradation of aromatic compounds in the R. wratislaviensis G10 and R. opacus 1CP strains isolated from sites of remote location (1400 km) and at different time (20-year difference) indicates a common origin of biodegradation genes of these strains and a wide distribution of these genes among rhodococci. PMID- 27682172 TI - Cell Wall Glycopolymers of Type Strains from Three Species of the Genus Actinoplanes. AB - The structures of cell wall glycopolymers from the type strains of three Actinoplanes species were investigated using chemical methods, NMR spectroscopy, and mass spectrometry. Actinoplanes digitatis VKM Ac-649(T) contains two phosphate-containing glycopolymers: poly(diglycosyl-1-phosphate) ->6)-alpha-D GlcpNAc-(1-P-6)-alpha-D-GlcpN-(1-> and teichoic acid ->1)-sn-Gro-(3-P-3)-beta [beta-D-GlcpNAc-(1->2]-D-Galp-(1->. Two glycopolymers were identified in A. auranticolor VKM Ac-648(T) and A. cyaneus VKM Ac-1095(T): minor polymer - unsubstituted 2,3-poly(glycerol phosphate), widely abundant in actinobacteria (Ac 648(T)), and mannan with trisaccharide repeating unit ->2)-alpha-D-Manp-(1->2) alpha-D-Manp-(1->6)-alpha-D-Manp-(1-> (Ac-1095(T)). In addition, both microorganisms contain a teichuronic acid of unique structure containing a pentasaccharide repeating unit with two residues of glucopyranose and three residues of diaminouronic acids in D-manno- and/or D-gluco-configuration. Each of the strains demonstrates peculiarities in the structure of teichuronic acid with respect to the ratio of diaminouronic acids and availability and location of O methyl groups in glucopyranose residues. All investigated strains contain a unique set of glycopolymers in their cell walls with structures not described earlier for prokaryotes. PMID- 27682173 TI - Identification of Proteins Whose Interaction with Na+,K+-ATPase Is Triggered by Ouabain. AB - Prolonged exposure of different epithelial cells (canine renal epithelial cells (MDCK), vascular endothelial cells from porcine aorta (PAEC), human umbilical vein endothelial cells (HUVEC), cervical adenocarcinoma (HeLa), as well as epithelial cells from colon carcinoma (Caco-2)) with ouabain or with other cardiotonic steroids was shown earlier to result in the death of these cells. Intermediates in the cell death signal cascade remain unknown. In the present study, we used proteomics methods for identification of proteins whose interaction with Na+,K+-ATPase is triggered by ouabain. After exposure of Caco-2 human colorectal adenocarcinoma cells with 3 uM of ouabain for 3 h, the protein interacting in complex with Na+,K+-ATPase was coimmunoprecipitated using antibodies against the enzyme alpha1-subunit. Proteins of coimmunoprecipitates were separated by 2D electrophoresis in polyacrylamide gel. A number of proteins in the coimmunoprecipitates with molecular masses of 71-74, 46, 40-43, 38, and 33 35 kDa was revealed whose binding to Na+,K+-ATPase was activated by ouabain. Analyses conducted by mass spectroscopy allowed us to identify some of them, including seven signal proteins from superfamilies of glucocorticoid receptors, serine/threonine protein kinases, and protein phosphatases 2C, Src-, and Rho GTPases. The possible participation of these proteins in activation of cell signaling terminated by cell death is discussed. PMID- 27682174 TI - Interaction of Telomeric Retroelement HeT-A Transcripts and Their Protein Product Gag in Early Embryogenesis of Drosophila. AB - The telomere is a nucleoprotein complex at the ends of linear chromosomes that protects them from fusion and degradation. The telomere consists of telomeric DNA, a protective protein complex and telomeric RNA. Biogenesis of telomeric transcripts in development is still far from being understood. Drosophila telomeres are elongated by a transposition of specialized telomeric retrotransposons that encode proteins. Using transgenic constructs encoding tagged telomeric protein, we found that transcripts of Drosophila telomeric element HeT-A bind Gag-HeT-A protein encoded by these transcripts. Maternal HeT-A transcripts and Gag-HeT-A form ribonucleoprotein granules around centrosomes, centers of microtubule organization, during blastoderm formation, upon disruption of telomere silencing during oogenesis. The specific localization of HeT-A RNA is dependent on microtubules since disruption of microtubules caused delocalization of HeT-A transcripts. This transgenic system is a valuable model for the study of telomeric RNA biogenesis. PMID- 27682175 TI - Adverse drug reactions of botulinum neurotoxin type A in children with cerebral palsy: a pharmaco-epidemiological study in VigiBase. AB - AIM: The aim of this study was to assess the risk of adverse drug reactions (ADRs) with botulinum neurotoxin type A (BoNT-A) in children with cerebral palsy (CP) using the World Health Organization global individual case safety report (ICSR) database, VigiBase. METHOD: We extracted all children ICSRs for ADRs with BoNT-A used as anti-spastic drug in CP recorded between 1995 and 2015 in VigiBase. We also performed a case/non-case method (disproportionality analysis) to assess the link between exposure to BoNT-A and each ADR of interest in children and adults, calculating reporting odds ratios (RORs). RESULTS: In VigiBase, 162 ICSRs were registered. They involved mainly males (n=95, 59%) and mean (SD) age was 7 years 11 months (4y 4mo). The most frequent ADR was dysphagia (27 ICSRs, 17%) followed by asthenia and muscular weakness (25 ICSRs each, 16%). Nineteen ICSRs (12%) were lethal. There was a significant association between BoNT-A and death in children (ROR=11.1 95%, confidence interval [CI] 7.0-17.7) but not in adults. INTERPRETATION: In children with CP, most ADRs seem to be linked to a systemic spread of BoNT-A. Our study suggests a higher risk of ADRs with BoNT-A in children than in adults. PMID- 27682176 TI - Copper/Zinc-Directed Heterometallic Uranyl-Organic Polycatenating Frameworks: Synthesis, Characterization, and Anion-Dependent Structural Regulation. AB - By employing a multidentate ligand, 2,2'-bipyridine-5,5'-dicarboxylic acid (H2bpdc), with both O-donors and N-donors, five uranyl-Cu(II)/Zn(II) heterometallic coordination polymers, (UO2)Cu(MU4-bpdc)(MU3-bpdc) (1-Cu), (UO2)Zn(MU4-bpdc)(MU3-bpdc) (1'-Zn), (UO2)CuCl(MU3-bpdc)(MU2-Hbpdc)(H2O) (2-Cu), (UO2)2Cu2Cl2(MU3-bpdc)2(MU2-Hbpdc)2(H2O)3.2H2O (2-Cu'), and (UO2)2Zn(MU3-SO4)(MU4 bpdc)(MU3-bpdc)(H2O)3 (3-Zn), were prepared under hydrothermal conditions. Thermal stability and luminescent properties of 1-Cu, 1'-Zn, 2-Cu, and 3-Zn were also investigated. Isostructural compounds 1-Cu and 1'-Zn both have a three dimensional (3D) framework built by polycatenating of two sets of paralleling two dimensional (2D) grids with octahedral transition metal cations (Cu or Zn) as the cross-linking nodes. As far as we know, compounds 1-Cu and 1'-Zn are the first two cases that possess polycatenated networks in heterometallic uranyl-organic coordination polymers. Compound 2-Cu contains 3-fold interpenetrated 2D networks which are built by the connection of [(UO2)2(bpdc)2(Hbpdc)2]2- secondary building units and Cu(II). A one-dimensional tilted ladder-like structure in 2-Cu' is constructed by uranyl-bpdc chains connected by Cu(II) and Hbpdc-. Compound 3-Zn displays a layered-like 2D network contain an unusual [(UO2)2Zn(MU3-SO4)] unit. Interestingly, different anions could lead to the change of coordination sites of transition metal cations, resulting in structural diversity of heterometallic uranyl-organic frameworks. PMID- 27682177 TI - ? PMID- 27682178 TI - Hypatulins A and B, Meroterpenes from Hypericum patulum. AB - Two novel prenylated benzophenone related meroterpenes, hypatulins A (1) and B (2), were isolated from the leaves of Hypericum patulum. The structures of 1 and 2 were assigned by spectroscopic analysis, chemical conversion, and calculations of the ECD (electron circular dichroism) spectra. Hypatulin A (1) had a unique densely substituted tricyclic octahydro-1,5-methanopentalene core, while hypatulin B (2) possessed a bicyclo[3.2.1]octane moiety. Hypatulin A (1) exhibited antimicrobacterial activity against Bacillus subtilis. A possible biogenetic pathway of the new meroterpenes 1 and 2 from a prenylated benzophenone was presented. PMID- 27682180 TI - Frontmatter. PMID- 27682179 TI - Hardware Technologies and Probe Development in Light Microscopy Help Drive Discoveries in Cell Biology: Introduction to a Virtual Symposium in The Biological Bulletin. PMID- 27682181 TI - Quantitative lateral flow strip assays as User-Friendly Tools To Detect Biomarker Profiles For Leprosy. AB - Leprosy is a debilitating, infectious disease caused by Mycobacterium leprae. Despite the availability of multidrug therapy, transmission is unremitting. Thus, early identification of M. leprae infection is essential to reduce transmission. The immune response to M. leprae is determined by host genetics, resulting in paucibacillary (PB) and multibacillary (MB) leprosy associated with dominant cellular or humoral immunity, respectively. This spectral pathology of leprosy compels detection of immunity to M. leprae to be based on multiple, diverse biomarkers. In this study we have applied quantitative user friendly lateral flow assays (LFAs) for four immune markers (anti-PGL-I antibodies, IL-10, CCL4 and IP 10) for whole blood samples from a longitudinal BCG vaccination field-trial in Bangladesh. Different biomarker profiles, in contrast to single markers, distinguished M. leprae infected from non-infected test groups, patients from household contacts (HHC) and endemic controls (EC), or MB from PB patients. The test protocol presented in this study merging detection of innate, adaptive cellular as well as humoral immunity, thus provides a convenient tool to measure specific biomarker profiles for M. leprae infection and leprosy utilizing a field friendly technology. PMID- 27682183 TI - Genome divergence and diversification within a geographic mosaic of coevolution. AB - Despite substantial interest in coevolution's role in diversification, examples of coevolution contributing to speciation have been elusive. Here, we build upon past studies that have shown both coevolution between South Hills crossbills and lodgepole pine (Pinus contorta), and high levels of reproductive isolation between South Hills crossbills and other ecotypes in the North American red crossbill (Loxia curvirostra) complex. We used genotyping by sequencing to generate population genomic data and applied phylogenetic and population genetic analyses to characterize the genetic structure within and among nine of the ecotypes. Although genome-wide divergence was slight between ecotypes (FST = 0.011-0.035), we found evidence of relative genetic differentiation (as measured by FST ) between and genetic cohesiveness within many of them. As expected for nomadic and opportunistic breeders, we detected no evidence of isolation by distance. The one sedentary ecotype, the South Hills crossbill, was genetically most distinct because of elevated divergence at a small number of loci rather than pronounced overall genome-wide divergence. These findings suggest that mechanisms related to recent local coevolution between South Hills crossbills and lodgepole pine (e.g. strong resource-based density dependence limiting gene flow) have been associated with genome divergence in the face of gene flow. Our results further characterize a striking example of coevolution driving speciation within perhaps as little as 6000 years. PMID- 27682182 TI - Beneficial Effects of Exogenous Melatonin in Acute Staphylococcus aureus and Escherichia coli Infection-Induced Inflammation and Associated Behavioral Response in Mice After Exposure to Short Photoperiod. AB - The administration of melatonin during acute bacterial infection was evaluated in this study. Mice pre-exposed to normal photoperiodic (NP), short photoperiodic (SP), and long photoperiodic (LP) day lengths were infected separately with live Staphylococcus aureus (5 * 106 cells/ml) or Escherichia coli (2.5 * 107 colony forming units/ml) and treated with melatonin (10 mg/kg body weight). Behavioral studies were performed before bacterial infection and after melatonin administration. In mice pre-exposed to SP, exogenous melatonin administration resulted in better clearance of bacteria from blood and behavioral improvement. Reduced glutathione content and superoxide dismutase activities were increased, with concomitant decrease in lipid peroxidation content and catalase activities in the liver, brain, and spleen after exogenous melatonin administration. The overproduction of tumor necrosis factor-alpha, interferon-gamma, and interleukin 6 during acute bacterial infection in mice exposed to different photoperiods was probably regulated by the administration of exogenous melatonin, by reducing neutrophil recruitment to spleen, expression of inducible nitric oxide synthase and cyclooxygenase-2 in hypothalamus, and C-reactive protein in the serum, and was also associated with improved behavioral response. Photoperiodic variations in inflammatory and oxidative stress markers might be correlated to serum melatonin and corticosterone levels. This study suggests that the administration of melatonin during SP exposure is protective in infection-induced inflammation than NP and LP exposure. PMID- 27682184 TI - Tracing of zinc and iron in experimentally induced varicocele: correlation with oxidative, nitrosative and carbonyl stress. AB - This study was designed to evaluate how varicocele (VCL) can time dependently induce zinc (Zn) and iron (Fe) toxicity in testicular tissue and to analyse the relation between heavy metals toxicity and lipid peroxidation, sperm DNA damage, nitrosative and carbonyl stresses. Twenty-four mature male Wistar rats were divided into control-sham and test groups, which were then submitted to experimentally induced VCL. Non-VCL-induced rats were considered as control-sham. The test groups were subdivided into three groups based on the sample collecting date (2, 6 and 8 months after VCL induction). Zn and Fe distribution in testicles, DNA ladder for sperm DNA fragmentation, testicular total antioxidant capacity (TAC), malondialdehyde (MDA), nitrite oxide (NO) and carbonyl groups (CG) were analysed. A significant (p < .05) enhancement in the percentage of tubules with negative tubular repopulation, differentiation and spermiogenesis indices was revealed. The VCL increased Zn and Fe distribution in testicles. The VCL, time dependently, reduced sperm count, motility and enhanced sperm DNA damage (p < .05). The VCL downregulated the testicular TAC and enhanced the MDA, NO and CG contents. Our data showed that the VCL results in intensive Fe and Zn toxicities. Produced Zn- and Fe-mediated-oxidative stress increases sperm DNA damage associated with NO and CG-induced stresses. PMID- 27682185 TI - Merging Iron Catalysis and Biocatalysis-Iron Carbonyl Complexes as Efficient Hydrogen Autotransfer Catalysts in Dynamic Kinetic Resolutions. AB - A dual catalytic iron/lipase system has been developed and applied in the dynamic kinetic resolution of benzylic and aliphatic secondary alcohols. A detailed study of the Knolker-type iron complexes demonstrated the hydrogen autotransfer of alcohols to proceed under mild reaction conditions and allowed the combination with the enzymatic resolution. Different racemic alcohols were efficiently converted to chiral acetates in good yields and with excellent enantioselectivities. PMID- 27682186 TI - Twelve months monitoring of hair GHB decay following a single dose administration in a case of facilitated sexual assault. PMID- 27682188 TI - The impact of postpartum post-traumatic stress disorder symptoms on child development: a population-based, 2-year follow-up study. AB - BACKGROUND: Against the background of very limited evidence, the present study aimed to prospectively examine the impact of maternal postpartum post-traumatic stress disorder (PTSD) symptoms on four important areas of child development, i.e. gross motor, fine motor, communication and social-emotional development. METHOD: This study is part of the large, population-based Akershus Birth Cohort. Data from the hospital's birth record as well as questionnaire data from 8 weeks and 2 years postpartum were used (n = 1472). The domains of child development that were significantly correlated with PTSD symptoms were entered into regression analyses. Interaction analyses were run to test whether the influence of postpartum PTSD symptoms on child development was moderated by child sex or infant temperament. RESULTS: Postpartum PTSD symptoms had a prospective relationship with poor child social-emotional development 2 years later. This relationship remained significant even when adjusting for confounders such as maternal depression and anxiety or infant temperament. Both child sex and infant temperament moderated the association between maternal PTSD symptoms and child social-emotional development, i.e. with increasing maternal PTSD symptom load, boys and children with a difficult temperament were shown to have comparatively higher levels of social-emotional problems. CONCLUSIONS: Examining four different domains of child development, we found a prospective impact of postpartum PTSD symptoms on children's social-emotional development at 2 years of age. Our findings suggest that both boys and children with an early difficult temperament may be particularly susceptible to the adverse impact of postpartum PTSD symptoms. Additional studies are needed to further investigate the mechanisms at work. PMID- 27682187 TI - Characteristics and outcomes of patients with multiple myeloma aged 21-40 years versus 41-60 years: a multi-institutional case-control study. AB - We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0.04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0.007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0.001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0.001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0.001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM. PMID- 27682189 TI - Activity of cefquinome against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in neutropenic mouse thigh model. AB - Increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) is of clinical concern. The objective of our study was to examine the in vivo activity of cefquinome against ESBL producing K. pneumoniae strain using a neutropenic mouse thigh infection model. Cefquinome kinetics and protein binding in infected neutropenic mice were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Dose fractionation studies over a 24-h dose range of 2.5-320 mg/kg were administered every 3, 6, 12, or 24 h. The percentage of the dosing interval that the free-drug serum levels exceed the MIC (%fT > MIC) was the PK-PD index that best correlated with cefquinome efficacy (R2 = 86%). Using a sigmoid Emax model, the magnitudes of %fT > MIC producing net bacterial stasis, a 1-log10 kill and a 2-log10 kill over 24 h, were estimated to be 20.07%, 29.57%, and 55.12%, respectively. These studies suggest that optimal cefquinome PK/PD targets are not achieved in pigs, sheep, and cattle at current recommended doses (1~2 mg/kg). Further studies with higher doses in the target species are needed to ensure therapeutic concentration, if cefquinome is used for treatment of K. pneumoniae infection. PMID- 27682190 TI - Autophagy function and its relationship to pathology, clinical applications, drug metabolism and toxicity. AB - Autophagy is a cellular process that facilitates nutrient turnover and removal of expended macromolecules and organelles to maintain homeostasis. The recycling of cytosolic macromolecules and damaged organelles by autophagosomes occurs through the lysosomal degradation pathway. Autophagy can also be upregulated as a prosurvival pathway in response to stress stimuli such as starvation, hypoxia or cell damage. Over the last two decades, there has been a surge in research revealing the basic molecular mechanisms of autophagy in mammalian cells. A corollary of an advanced understanding of autophagy has been a concurrent expansion of research into understanding autophagic function and dysfunction in pathology. Recent studies have revealed a pivotal role for autophagy in drug toxicity, and for utilizing autophagic components as diagnostic markers and therapeutic targets in treating disease and cancer. In this review, advances in understanding the molecular basis of mammalian autophagy, methods used to induce and evaluate autophagy, and the diverse interactions between autophagy and drug toxicity, disease progression and carcinogenesis are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27682192 TI - Junior doctors lose legal challenge over contract imposition. PMID- 27682191 TI - Towards national comprehensive gestational diabetes screening - consequences for neonatal outcome and care. AB - INTRODUCTION: The change from risk-factor-based to nearly comprehensive screening of gestational diabetes (GDM) identifies more but milder cases of the disease. The main aim of this study was to evaluate the effect of this screening policy change on neonatal outcomes and care. MATERIAL AND METHODS: A population-based register study in Finland. GDM cases during risk-factor-based (year 2006, n = 5179) and comprehensive (2010, n = 6679) screenings were identified through the Medical Birth Register. All singletons without maternal GDM or prepregnancy diabetes served as controls (n = 51 746 and n = 52 386, respectively). The main outcomes were macrosomia, neonatal hypoglycemia and the need for care in a neonatal ward. RESULTS: In the GDM group, the mean birthweight decreased between the study years from 3660 g to 3595 g and the prevalence of macrosomia from 5.6 to 4.1% even after adjustment for maternal age, parity and prepregnancy body mass index. The adjusted mean difference in birthweight between GDM and control newborns decreased from 70 to 22 g between the study years. The prevalence of neonatal hypoglycemia increased from 18.0 to 22.1% in the GDM group. However, neonatal hypoglycemia was more often treated without care in a neonatal ward. The proportion of infants treated on a neonatal ward decreased in both the GDM and control groups between the study years. CONCLUSIONS: In newborns, comprehensive GDM screening led to decreased mean birthweight and macrosomia rates, but the prevalence of neonatal hypoglycemia increased. This places substantial demands for delivery hospitals and healthcare resources. PMID- 27682193 TI - Surfactant-Free Emulsions with Erasable Triggered Phase Inversions. AB - Complex emulsions including double emulsions and high-internal-phase emulsions (HIPEs) are wonderful templates for producing porous polymeric materials. Yet, surfactants and multiple emulsifications are generally needed. In this work, surfactant-free complex emulsions are successfully prepared using a CO2 responsive block copolymer through one-step emulsification. Phase inversion from HIPEs to double emulsions happens in one system upon the change in polymer amphiphilicity as a result of CO2 triggering. The one-step emulsification method offers great convenience for converting the block copolymer into porous 3D scaffolds and particles. Moreover, CO2 triggering is erasable so that the polymer can be repeatedly used for controllable complex emulsions as well as porous materials. PMID- 27682194 TI - Examination of Trifluoroethanol Interactions with Trp-Cage through MD Simulations and Intermolecular Nuclear Overhauser Effects. AB - Molecular dynamics simulations of the protein model Trp-cage in 42% 2,2,2 trifluoroethanol (TFE)-water at 318 K have been carried out with the goal of exploring solvent fluorine-peptide hydrogen nuclear spin cross-relaxation. TFE5 and TFE6 models of TFE developed in previous work from this laboratory were used with the TIP5PE model of water. System densities and component translational diffusion coefficients were well predicted by the simulations, as were many of the cross-relaxation parameters (SigmaHF) for which experimental values are available. However, the calculated SigmaHF values were too small for some hydrogens of the Trp6 indole ring and for amino acid hydrogens near this residue in the native structure. Simulations carried out with unfolded versions of Trp cage suggest that underestimates of SigmaHF are the result of insufficient sampling of conformational motions that expose these hydrogens to interactions with solvent molecules during simulations of the native peptide. Consideration of the relative amounts of TFE and water surrounding the Trp-cage structure indicates that the composition of the solvent mixture at distances beyond ~1.5 nm from the surface of the peptide is close to the composition of the bulk solvent, but, as observed by others, TFE tends to accumulate preferentially near the surface of the peptide. Both TFE and water molecules make contacts with the peptide surface; water molecules predominate in contacts with the peptide backbone atoms, and TFE molecules generally preferentially interact with side chains. Translational diffusion of solvent molecules appears to slow down near the surface of the peptide. PMID- 27682195 TI - Albumin-Binding Evans Blue Derivatives for Diagnostic Imaging and Production of Long-Acting Therapeutics. AB - One of the major design considerations for a drug is its pharmacokinetics: a drug with short blood half-life is less available at a target organ which in turn dictates treatment with either high or more frequent doses, and increases the likelihood of undesirable side effects. One method to improve drug pharmacokinetics is adding functional chemical groups to the drug molecule that can increase the half-life in the blood, hopefully, without significantly affecting its desired biological activity. Evans Blue (EB) dye reversibly binds to serum albumin with moderate affinity and has a long blood half-life. The binding of EB to albumin has been exploited to quantify protein leakage as an indicator of increased vascular permeability. Design of new chemical entities based on EB structure and coupling them to drugs, enables the usage of albumin as a reversible carrier in the blood and improves drug's half-life. This Topical Review summarizes the recent developments of various EB derivatives for molecular imaging and therapy applications. PMID- 27682197 TI - Functional Diversity and Microbial Activity of Forest Soils that Are Heavily Contaminated by Lead and Zinc. AB - The objective of this study was to assess the impact of metal contamination on microbial functional diversity and enzyme activity in forest soils. This study involved the evaluation of the influence of the texture, carbon content and distance to the source of contamination on the change in soil microbial activity, which did not investigate in previous studies. The study area is located in southern Poland near the city of Olkusz around the flotation sedimentation pond of lead and zinc at the Mining and Metallurgical Company "ZGH Boleslaw, Inc.". The central point of the study area was selected as the middle part of the sedimentation pond. The experiment was conducted over a regular 500 * 500-m grid, where 33 sampling points were established. Contents of organic carbon and trace elements (Zn, Pb and Cd), pH and soil texture were investigated. The study included the determination of dehydrogenase and urease activities and microbial functional diversity evaluation based on the community-level physiological profiling approach by Biolog EcoPlate. The greatest reduction in the dehydrogenase and urease activities was observed in light sandy soils with Zn content >220 mg . kg-1 and a Pb content > 100 mg . kg-1. Soils with a higher concentration of fine fraction, despite having the greatest concentrations of metals, were characterized by high rates of Biolog(r)-derived parameters and a lower reduction of enzyme activity. PMID- 27682196 TI - The Plasma Protein Binding Proteome of Ertapenem: A Novel Compound-Centric Proteomic Approach for Elucidating Drug-Plasma Protein Binding Interactions. AB - Ertapenem is an important first-line carbapenem antibiotic used for the treatment of aerobic Gram-negative bacterial infections. It is the only marketed carbapenem that is highly bound to plasma proteins and displays a concentration-dependent and saturable plasma protein binding profile. To date, the plasma components responsible for sequestering ertapenems antibacterial activity remain uncharacterized. In the present study, we have employed an orthogonal, multiplatform approach, including novel compound-centric displacement proteomics and surface plasmon resonance to characterize the plasma protein binding proteome of ertapenem. In proof-of-concept, the capacity of physiological cocktails of the identified plasma proteins to inhibit the antibacterial activity of ertapenem was assessed with in vitro microbiological assays. We show that fibrinogen, complement C4, haptoglobulin, alpha-1-antitrypsin, fibronectin, transferrin, immunoglobulin G, hemopexin, and humans serum albumin are responsible for the majority of the sequestering activity in plasma. No binding was observed to alpha 1-acid-glycoprotein. The findings of this study have broad reaching implications for antibiotic drug design and for dose tailoring to suit the plasma protein levels of individual patients in order to maximize the clinical efficacy of important first-line antibiotics such as ertapenem. PMID- 27682198 TI - Interaction Between Cadmium Stress and Sulphur Nutrition Level on Macronutrient Status of Sinapis alba L. AB - This study evaluated the possibility of improving the macronutrient status of Cd stressed white mustard 'Rota' using intensive S nutrition. Three S-SO4 (2, 6, 9 mM S) and four CdCl2 doses (0, 0.0002, 0.02, 0.04 mM Cd) in the Hoagland's nutrient solution were conducted for 14 days. High S supply (6 or 9 mM) appears, to some extent, to affect positively the macronutrient status of Cd-stressed mustard. It increased roots and shoots contents of K and S, without significant changes in P content. Simultaneously, Mg content in shoots and roots remained stable, but Mg bioaccumulation was elevated. Shoot Ca content at the lowest and medium Cd dose decreased, whilst was unaffected at the highest Cd treatment. Intensive S nutrition of Cd-stressed mustard increased root N content and accumulation at the highest Cd concentration, but the N content dropped in above ground parts. The bioaccumulation of remained macronutrients in general was substantially elevated together with enhanced Cd accumulation. Thus, the intensive S nutrition can enhance mustard tolerance to Cd stress by improvement macronutrients relations in plants, and S supplementation may be recommended for mustard cultivation on the Cd-contaminated areas. PMID- 27682199 TI - Cyclobutane Thymine Photodimerization Mechanism Revealed by Nonadiabatic Molecular Dynamics. AB - The formation of cyclobutane thymine dimers is one of the most important DNA carcinogenic photolesions induced by ultraviolet irradiation. The long debated question whether thymine dimerization after direct light excitation involves singlet or triplet states is investigated here for the first time using nonadiabatic molecular dynamics simulations. We find that the precursor of this [2 + 2] cycloaddition reaction is the singlet doubly pi2pi*2 excited state, which is spectroscopically rather dark. Excitation to the bright 1pipi* or dark 1npi* excited states does not lead to thymine dimer formation. In all cases, intersystem crossing to the triplet states is not observed during the simulated time, indicating that ultrafast dimerization occurs in the singlet manifold. The dynamics simulations also show that dimerization takes place only when conformational control happens in the doubly excited state. PMID- 27682200 TI - HRD Motif as the Central Hub of the Signaling Network for Activation Loop Autophosphorylation in Abl Kinase. AB - A number of structural factors modulate the activity of Abelson (Abl) tyrosine kinase, whose deregulation is often related to oncogenic processes. First, only the open conformation of the Abl kinase domain's activation loop (A-loop) favors ATP binding to the catalytic cleft. In this regard, the trans-autophosphorylation of the Y412 residue, which is located along the A-loop, favors the stability of the open conformation, in turn enhancing Abl activity. Another key factor for full Abl activity is the formation of active conformations of the catalytic DFG motif in the Abl kinase domain. Furthermore, binding of the SH2 domain to the N lobe of the Abl kinase was recently demonstrated to have a long-range allosteric effect on the stabilization of the A-loop open state. Intriguingly, these distinct structural factors imply a complex signal transmission network for controlling the A-loop's flexibility and conformational preference for optimal Abl function. However, the exact dynamical features of this signal transmission network structure remain unclear. Here, we report on microsecond-long molecular dynamics coupled with enhanced sampling simulations of multiple Abl model systems, in the presence or absence of the SH2 domain and with the DFG motif flipped in two ways (in or out conformation). Through comparative analysis, our simulations augment the interpretation of the existing Abl experimental data, revealing a dynamical network of interactions that interconnect SH2 domain binding with A-loop plasticity and Y412 autophosphorylation in Abl. This signaling network engages the DFG motif and, importantly, other conserved structural elements of the kinase domain, namely, the EPK-ELK H-bond network and the HRD motif. Our results show that the signal propagation for modulating the A loop spatial localization is highly dependent on the HRD motif conformation, which thus acts as the central hub of this (allosteric) signaling network controlling Abl activation and function. PMID- 27682201 TI - [What do the members of the Spanish Society of Geriatrics and Gerontology think about clinical practice guidelines in geriatrics?] PMID- 27682202 TI - Novel genotype of Ehrlichia canis detected in samples of human blood bank donors in Costa Rica. AB - This study focuses on the detection and identification of DNA and antibodies to Ehrlichia spp. in samples of blood bank donors in Costa Rica using molecular and serological techniques. Presence of Ehrlichia canis was determined in 10 (3.6%) out of 280 blood samples using polymerase chain reaction (PCR) targeting the ehrlichial dsb conserved gene. Analysis of the ehrlichial trp36 polymorphic gene in these 10 samples revealed substantial polymorphism among the E. canis genotypes, including divergent tandem repeat sequences. Nucleotide sequences of dsb and trp36 amplicons revealed a novel genotype of E. canis in blood bank donors from Costa Rica. Indirect immunofluorescence assay (IFA) detected antibodies in 35 (35%) of 100 serum samples evaluated. Thirty samples showed low endpoint titers (64-256) to E. canis, whereas five sera yielded high endpoint titers (1024-8192); these five samples were also E. canis-PCR positive. These findings represent the first report of the presence of E. canis in humans in Central America. PMID- 27682203 TI - Considering sex as a biological variable in preclinical research. AB - In June 2015, the National Institutes of Health (NIH) released a Guide notice (NOT-OD-15-102) that highlighted the expectation of the NIH that the possible role of sex as a biologic variable be factored into research design, analyses, and reporting of vertebrate animal and human studies. Anticipating these guidelines, the NIH Office of Research on Women's Health, in October 2014, convened key stakeholders to discuss methods and techniques for integrating sex as a biologic variable in preclinical research. The workshop focused on practical methods, experimental design, and approaches to statistical analyses in the use of both male and female animals, cells, and tissues in preclinical research. Workshop participants also considered gender as a modifier of biology. This article builds on the workshop and is meant as a guide to preclinical investigators as they consider methods and techniques for inclusion of both sexes in preclinical research and is not intended to prescribe exhaustive/specific approaches for compliance with the new NIH policy.-Miller, L. R., Marks, C., Becker, J. B., Hurn, P. D., Chen, W.-J., Woodruff, T., McCarthy, M. M., Sohrabji, F., Schiebinger, L., Wetherington, C. L., Makris, S., Arnold, A. P., Einstein, G., Miller, V. M., Sandberg, K., Maier, S., Cornelison, T. L., Clayton, J. A. Considering sex as a biological variable in preclinical research. PMID- 27682204 TI - The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages. AB - The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1beta, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately determine the phenotype of differentiated T cells, thus creating an immune environment that is conducive to sustaining chronic infection. We show that one of these molecules, FhHDM-1, a cathelicidin-like peptide secreted by the helminth parasite, Fasciola hepatica, inhibits the activation of the NLRP3 inflammasome resulting in reduced secretion of IL-1beta by macrophages. FhHDM-1 had no effect on the synthesis of pro-IL-1beta. Rather, the inhibitory effect was associated with the capacity of the peptide to prevent acidification of the endolysosome. The activation of cathepsin B protease by lysosomal destabilization was prevented in FhHDM-1 treated macrophages. By contrast, peptide derivatives of FhHDM-1 that did not alter the lysosomal pH did not inhibit secretion of IL-1beta. We propose a novel immune modulatory strategy used by F. hepatica, whereby secretion of the FhHDM-1 peptide impairs the activation of NLRP3 by lysosomal cathepsin B protease, which prevents the downstream production of IL-1beta and the development of protective T helper 1 type immune responses that are detrimental to parasite survival. Alvarado, R., To, J., Lund, M. E., Pinar, A., Mansell, A., Robinson, M. W., O'Brien, B. A., Dalton, J. P., Donnelly, S. The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages. PMID- 27682205 TI - Impact of endurance exercise training on adipocyte microRNA expression in overweight men. AB - Adipocytes are major regulators of metabolism, and endurance exercise training improves adipocyte function; however, the molecular mechanisms that regulate chronic adaptive responses remain unresolved. microRNAs (miRNAs) influence adipocyte differentiation and metabolism. Accordingly, we aimed to determine whether adipocyte miRNA expression is responsive to exercise training and to identify exercise-responsive miRNAs that influence adipocyte metabolism. Next generation sequencing was used to profile miRNA expression of adipocytes that were isolated from abdominal subcutaneous (ABD) and gluteofemoral (GF) adipose tissue of overweight men before and after 6 wk of endurance exercise training. Differentially expressed miRNAs were overexpressed or silenced in 3T3-L1 adipocytes, and lipid metabolism was examined. Next-generation sequencing identified 526 miRNAs in adipocytes, and there were no statistical differences in miRNA expression when comparing pre- and post-training samples for ABD and GF adipocytes. miR-10b expression was increased in ABD compared with GF adipocytes, whereas miR-204, miR-3613, and miR-4532 were more highly expressed in GF compared with ABD adipocytes. Blocking miR-10b in adipocytes suppressed beta-adrenergic lipolysis but generally had a minor effect on lipid metabolism. Thus, unlike their critical role in adipogenesis, stable changes in miRNA expression do not play a prominent role in the regulation of adipocyte function in response to endurance exercise training.-Tsiloulis, T., Pike, J., Powell, D., Rossello, F. J., Canny, B. J., Meex, R. C. R., Watt, M. J. Impact of endurance exercise training on adipocyte microRNA expression in overweight men. PMID- 27682206 TI - In vivo study of the role of alpha6-containing nicotinic acetylcholine receptor in retinal function using subtype-specific RDP-MII(E11R) toxin. AB - Although alpha6-contaning (alpha6*) nicotinic acetylcholine receptors (nAChRs) are densely expressed in the visual system, their role is not well known. We have characterized a family of toxins that are antagonists for alpha6beta2* receptors and used one of these [RDP-MII(E11R)] to localize alpha6* nAChRs and investigate their impact on retinal function in adult Long-Evans rats. The alpha6*nAChRs in retinal tissue were localized using either a fluorescently tagged [RDP-MII(E11R)] or anti-alpha6-specific antibodies and found to be predominantly at the level of the ganglion cell layer. After intraocular injection of RDP-MII(E11R) in one eye and vehicle or inactive MII in contralateral eyes as controls, we recorded flash electroretinograms (F-ERGs), pattern ERGs (P-ERGs), and cortical visual-evoked potential (VEPs). There was no significant difference in F-ERG between the RDP MII(E11R)-treated and control eyes. In contrast, P-ERG response amplitude was significantly reduced in the RDP-MII(E11R)-injected eye. Blocking alpha6* nAChRs at retinal level also decreased the VEP amplitude recorded in the visual cortex contralateral to the injected eye. Because both the cortical and inner retina output were affected by RDP-MII(E11R), whereas photoreceptor output was preserved, we conclude that the reduced visual response was due to an alteration in the function of alpha6* nAChRs present in the ganglion cell layer.-Barloscio, D., Cerri, E., Domenici, L., Longhi, R., Dallanoce, C., Moretti, M., Vilella, A., Zoli, M., Gotti, C., and Origlia, N. In vivo study of the role of alpha6 containing nicotinic acetylcholine receptor in retinal function using subtype specific RDP-MII(E11R) toxin. PMID- 27682207 TI - Long-term outcomes from training in self-management of chronic pain in an elderly population: a randomized controlled trial. AB - This study compares the outcomes, from pretreatment to 1-year follow-up, of an outpatient, CBT-based pain self-management program (PSM) that included exercises, pain education, and pain coping strategies, with a control condition (exercise attention control, EAC) that included exercises and a control for the attention of the treatment team. We previously reported short-term results (to 1-month follow-up) from the same study. This new paper considers the important issue of maintenance of treatment-related gains. The participants (n = 141) were a heterogeneous sample of ambulant, community-dwelling older adult patients with chronic pain (mean age: 73.90 [6.5] years [range: 65-87 years]). The long-term results indicate the pain self-management program group achieved and maintained significantly better results than the exercise-attention control group on the primary outcome, pain-related disability, as well as on usual pain, pain distress, depression, and fear-avoidance beliefs. The mean effect size for these gains by the pain self-management program group over the exercise-attention control group was 0.37 (range: 0.29-0.45), which is in the small effect size range. While statistically and clinically meaningful, these findings do indicate some weakening in effects over time but not to a significant degree. The study has implications for the provision of pain management interventions for community dwelling older adults with chronic pain. PMID- 27682208 TI - Racial and ethnic differences in experimental pain sensitivity: systematic review and meta-analysis. AB - Our objective was to describe the racial and ethnic differences in experimental pain sensitivity. Four databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO) were searched for studies examining racial/ethnic differences in experimental pain sensitivity. Thermal-heat, cold pressor, pressure, ischemic, mechanical cutaneous, electrical, and chemical experimental pain modalities were assessed. Risk of bias was assessed using the Agency for Healthcare Research and Quality guideline. Meta-analysis was used to calculate standardized mean differences (SMDs) by pain sensitivity measures. Studies comparing African Americans (AAs) and non-Hispanic whites (NHWs) were included for meta-analyses because of high heterogeneity in other racial/ethnic group comparisons. Statistical heterogeneity was assessed by subgroup analyses by sex, sample size, sample characteristics, and pain modalities. A total of 41 studies met the review criteria. Overall, AAs, Asians, and Hispanics had higher pain sensitivity compared with NHWs, particularly lower pain tolerance, higher pain ratings, and greater temporal summation of pain. Meta-analyses revealed that AAs had lower pain tolerance (SMD: -0.90, 95% confidence intervals [CIs]: -1.10 to -0.70) and higher pain ratings (SMD: 0.50, 95% CI: 0.30-0.69) but no significant differences in pain threshold (SMD: -0.06, 95% CI: -0.23 to 0.10) compared with NHWs. Estimates did not vary by pain modalities, nor by other demographic factors; however, SMDs were significantly different based on the sample size. Racial/ethnic differences in experimental pain sensitivity were more pronounced with suprathreshold than with threshold stimuli, which is important in clinical pain treatment. Additional studies examining mechanisms to explain such differences in pain tolerance and pain ratings are needed. PMID- 27682209 TI - A rodent model of HIV protease inhibitor indinavir induced peripheral neuropathy. AB - HIV-associated sensory neuropathy (HIV-SN) is the most frequent manifestation of HIV disease. It often presents with significant neuropathic pain and is associated with previous exposure to neurotoxic nucleoside reverse transcriptase inhibitors. However, HIV-SN prevalence remains high even in resource-rich settings where these drugs are no longer used. Previous evidence suggests that exposure to indinavir, a protease inhibitor commonly used in antiretroviral therapy, may link to elevated HIV-SN risk. Here, we investigated whether indinavir treatment was associated with the development of a "dying back" axonal neuropathy and changes in pain-relevant limb withdrawal and thigmotactic behaviours. After 2 intravenous injections of indinavir (50 mg/kg, 4 days apart), adult rats developed hind paw mechanical hypersensitivity, which peaked around 2 weeks post first injection (44% reduction from baseline). At this time, animals also had (1) significantly changed thigmotactic behaviour (62% reduction in central zone entries) comparing with the controls and (2) a significant reduction (45%) in hind paw intraepidermal nerve fibre density. Treatment with gabapentin, but not amitriptyline, was associated with a complete attenuation of hind paw mechanical hypersensitivity observed with indinavir treatment. Furthermore, we found a small but significant increase in microglia with the effector morphology in the lumbar spinal dorsal horn in indinavir-treated animals, coupled with significantly increased expression of phospho-p38 in microglia. In summary, we have reported neuropathic pain-related sensory and behavioural changes accompanied by a significant loss of hind paw skin sensory innervation in a rat model of indinavir-induced peripheral neuropathy that is suitable for further pathophysiological investigation and preclinical evaluation of novel analgesics. PMID- 27682211 TI - The time course of acute pain in hospitalized patients: exciting progress in data and methods. PMID- 27682210 TI - Differential expression of systemic inflammatory mediators in amputees with chronic residual limb pain. AB - Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Subjects included 36 recent active duty military traumatic amputees with chronic residual limb pain and 40 without clinically significant pain. Blood samples were obtained and plasma concentrations of an array of inflammatory mediators were analyzed. Residual limb pain intensity and pain catastrophizing were assessed to examine associations with inflammatory mediators. Pro-inflammatory mediators including tumor necrosis factor (TNF)-alpha, TNF-beta, interleukin (IL)-8, ICAM-1, Tie2, CRP, and SAA were elevated in patients with chronic residual limb pain. Across all patients, residual limb pain intensity was associated positively with levels of several proinflammatory mediators (IL-8, TNF-alpha, IL-12, TNF-beta, PIGF, Tie2, SAA, and ICAM-1), and inversely with concentrations of the anti-inflammatory mediator IL 13, as well as IL-2 and Eotaxin-3. Pain catastrophizing correlated positively with IL-8, IL-12, TNF-beta, PIGF, and ICAM-1, and inversely with IL-13. Significant associations between catastrophizing and residual limb pain intensity were partially mediated by TNF-alpha, TNF- beta, SAA, and ICAM-1 levels. Results suggest that chronic postamputation residual limb pain is associated with excessive inflammatory response to injury or to inadequate resolution of the postinjury inflammatory state. Impact of pain catastrophizing on residual limb pain may be because of part to common underlying inflammatory mechanisms. PMID- 27682213 TI - The management of neonatal acute and chronic renal failure: A review. AB - Most babies with chronic renal failure are identified antenatally, and over half that are treated with peritoneal dialysis receive kidney transplants before school age. Most infants that develop acute renal failure have hypotension following cardiac surgery, or multiple organ failure. Sometimes the falls in glomerular filtration and urine output are physiological and reversible, and sometimes due to kidney injury, but (illogically) it is now common to define them all as having 'acute kidney injury'. Contrary to widespread opinion, careful interpretation of the plasma creatinine concentrations can provide sensitive evidence of early acute renal failure. Conservative management frequently leads to under-nutrition or fluid overload. Acute peritoneal dialysis is often technically fraught in very small patients, and haemotherapies have been limited by vascular access and anticoagulation requirements, the need to blood-prime circuits, and serious limitations in regulating fluid removal. Newer devices, including the Nidus, have been specifically designed to reduce these difficulties. PMID- 27682212 TI - Current and developing therapies for the treatment of non-small cell lung cancer with ALK abnormalities: update and perspectives for clinical practice. AB - INTRODUCTION: The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1. Given that resistance occurs within approximately 12 months, in order to develop more potent inhibitors and to increase drug penetration to CNS, innovative ALK-inhibitors were developed. Second-generation ALK inhibitors Ceritinib (LDK378), Alectinib (CH5424802/RO5424802) and Brigatinib (AP26113) have shown significant clinical activity, and were rapidly approved by regulatory agencies. In addition, early clinical data demonstrated that 3rd generation ALK-inhibitors Lorlatinib (PF 06463922), Entrectinib (RxDx-101) and Ensartinib (X-398) provided promising advantages in terms of both clinical activity and safety. Areas covered: In this review, the efficacy and tolerability of Crizotinib for 1st and 2nd-line treatment, and the clinical and preclinical data that led to the development of innovative second and third generation ALK-inhibitors are described. Expert opinion: The better characterization of the mechanisms of resistance to Crizotinib led to the development of newest drugs, which are active both after Crizotinib failure and in patients naive from ALK-inhibitors. Tumor characterization at disease progression will allow to further personalize the treatment by establishing optimal sequences, which represent tough challenges for the future research in this field of cancer treatment. PMID- 27682214 TI - Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway. AB - Lung cancer has been a leading cause of cancer mortality worldwide and aerosol mediated gene therapy endows numerous advantages compared to other traditional modalities. Here, we reported a folic acid (FA)-modified hyperbranched polyspermine (HPSPE) with prominent biocompatibility for lung cancer cell targeted gene therapy. FA was decorated to the HPSPE via an amidation reaction and the physicochemical properties of nanoplexes formed with DNA were characterized. Gel electrophoresis study elucidated that the designed polymer was capable to condense DNA and protect it from degradation by DNase I. Cell viability and transfection efficiency assay in vitro and in vivo indicated its increased transfection performance with lower toxicity. Furthermore, reduced tumor numbers and down-regulation of Akt1 protein after aerosol treatment containing FA-HPSPE/shAkt1 complexes proved its therapeutic potential for lung cancer suppression. Results obtained in this study suggested that FA-HPSPE with highly biocompatibility and targeting capability while forming complexes with shAkt1 and administrated through noninvasive aerosol could be prospective for inhibiting lung tumorigenesis. PMID- 27682215 TI - One-step assembly of polymeric demethylcantharate prodrug/Akt1 shRNA complexes for enhanced cancer therapy. AB - This report demonstrated a one-step assembly for co-delivering chemotherapeutics and therapeutic nucleic acids, constructed by integrating drug molecules into a nucleic acid condensing polymeric prodrug through degradable linkages. Demethylcantharate was selected as the model drug and pre-modified by esterifying its two carboxylic groups with 2-hydroxyethyl acrylate. The synthesized demethylcantharate diacrylate was then used to polymerize with linear polyethyleneimine (PEI 423) through a one-step Michael-addition reaction. The obtained cationic polymeric demethylcantharate prodrug was used to pack Akt1 shRNA into complexes through a one-step assembly. The formed complexes could release the parent drug demethylcantharate and Akt1 shRNA through the hydrolysis of ester bonds. Cellular assays involving cell uptake, cytotoxicity, and cell migration indicated that demethylcantharate and Akt1 shRNA co-delivered in the present form significantly and synergistically suppress the growth and metastasis of three human cancer cells. This work suggests that incorporating drug molecules into a nucleic acid-packing cationic polymer as a polymeric prodrug in a degradable form is a highly convenient and efficient way to co-deliver drugs and nucleic acids for cancer therapy. PMID- 27682217 TI - Time-resolved fluorescence observation of di-tyrosine formation in horseradish peroxidase upon ultrasound treatment leading to enzyme inactivation. AB - The application of ultrasound to a solution can induce cavitional phenomena and generate high localised temperatures and pressures. These are dependent of the frequency used and have enabled ultrasound application in areas such as synthetic, green and food chemistry. High frequency (100kHz to 1MHz) in particular is promising in food chemistry as a means to inactivate enzymes, replacing the need to use periods of high temperature. A plant enzyme, horseradish peroxidase, was studied using time-resolved fluorescence techniques as a means to assess the effect of high frequency (378kHz and 583kHz) ultrasound treatment at equivalent acoustic powers. This uncovered the fluorescence emission from a newly formed species, attributed to the formation of di-tyrosine within the horseradish peroxidase structure caused by auto-oxidation, and linked to enzyme inactivation. PMID- 27682218 TI - Understanding the complexation of Eu3+ with potential ligands used for preferential separation of lanthanides and actinides in various stages of nuclear fuel cycle: A luminescence investigation. AB - A systematic photoluminescence based investigation was carried out to understand the complexation of Eu3+ with different ligands (TBP: tri-n-butyl phosphate, DHOA: di-n-hexyl octanamide, Cyanex 923: tri-n-alkyl phosphine oxide and Cyanex 272: Bis (2,4,4 trimethyl) pentyl phosphinic acid) used for preferential separation of lanthanides and actinides in various stages of nuclear fuel cycle. In case of TBP and DHOA complexes, 3 ligand molecules coordinated in monodentate fashion and 3 nitrate ion in bidentate fashion to Eu3+ to satisfy the 9 coordination of Eu. In case of Cyanex 923 and Cyanex 272 complexes, 3 ligand molecules, 3 nitrate ion and 3 water molecules coordinated to Eu3+ in monodentate fashion. The Eu complexes of TBP and DHOA were found to have D3h local symmetry while that for Cyanex 923 and Cyanex 272 were C3h. Judd-Ofelt analysis of these systems revealed that the covalency of EuO bond followed the trend DHOA>TBP>Cyanex 272>Cyanex 923. Different photophysical properties like radiative and non-radiative life time, branching ratio for different transitions, magnetic and electric dipole moment transition probabilities and quantum efficiency were also evaluated and compared for these systems. The magnetic dipole transition probability was found to be almost independent of ligand field perturbation while electric dipole transition probability for 5D0-7F2 transition was found to be hypersensitive with ligand field with a trend DHOA>TBP>Cyanex 272>Cyanex 923. PMID- 27682216 TI - Is Exposure to Macondo Oil Reflected in the Otolith Chemistry of Marsh-Resident Fish? AB - Genomic and physiological responses in Gulf killifish (Fundulus grandis) in the northern Gulf of Mexico have confirmed oil exposure of resident marsh fish following the Macondo blowout in 2010. Using these same fish, we evaluated otolith microchemistry as a method for assessing oil exposure history. Laser ablation inductively-coupled-plasma mass spectrometry was used to analyze the chemical composition of sagittal otoliths to assess whether a trace metal signature could be detected in the otoliths of F. grandis collected from a Macondo-oil impacted site in 2010, post-spill relative to pre-spill, as well as versus fish from areas not impacted by the spill. We found no evidence of increased concentrations of two elements associated with oil contamination (nickel and vanadium) in F. grandis otoliths regardless of Macondo oil exposure history. One potential explanation for this is that Macondo oil is relatively depleted of those metals compared to other crude oils globally. During and after the spill, however, elevated levels of barium, lead, and to a lesser degree, copper were detected in killifish otoliths at the oil-impacted collection site in coastal Louisiana. This may reflect oil contact or other environmental perturbations that occurred concomitant with oiling. For example, increases in barium in otoliths from oil-exposed fish followed (temporally) freshwater diversions in Louisiana in 2010. This implicates (but does not conclusively demonstrate) freshwater diversions from the Mississippi River (with previously recorded higher concentrations of lead and copper), designed to halt the ingress of oil, as a mechanism for elevated elemental uptake in otoliths of Louisiana marsh fishes. These results highlight the potentially complex and indirect effects of the Macondo oil spill and human responses to it on Gulf of Mexico ecosystems, and emphasize the need to consider the multiple stressors acting simultaneously on inshore fish communities. PMID- 27682220 TI - The gastrin receptor antagonist netazepide (YF476) in patients with type 1 gastric enterochromaffin-like cell neuroendocrine tumours: review of long-term treatment. AB - OBJECTIVE: Netazepide (YF476) is a recently developed, orally active gastrin receptor antagonist that, in short trials in patients with type 1 gastric enterochromaffin-like cell neuroendocrine tumours, has been shown to induce a significant reduction in the number and size of tumours as well as serum chromogranin A (CgA). The aim of this review is to evaluate the long-term effect and safety of netazepide. PATIENTS AND METHODS: Five patients previously treated with netazepide in an open-label trial were offered continuous treatment with netazepide 25 mg once daily. Upper endoscopy was performed every 6 months. The tumours were counted and measured, and tissue samples were obtained from the flat corpus mucosa. Enterochromaffin-like cell hyperplasia was classified according to Solcia and colleagues and volume density of CgA immunoreactive (IR) cells was calculated. Fasting serum CgA and fasting serum gastrin were measured every 3 months. RESULTS: All tumours regressed completely in three of five patients; time until total disappearance was 3, 9 and 12 months. In the other two patients, the number of tumours was reduced from 13 to 5 and from 14 to 3. Serum CgA showed a rapid and sustained decrease (P<0.001). The mean reduction in serum CgA was 4.1+/ 0.5 nmol/l. Similarly, volume density of CgA IR cells in the flat corpus mucosa decreased (P<0.001), with the mean change being 2.0+/-0.4%. Serum gastrin and volume density of gastrin IR cells in the antral part of the stomach remained unchanged (P=0.2 and 0.7, respectively). CONCLUSION: Long-term administration of netazepide is effective and safe. PMID- 27682221 TI - Association Between Postoperative Admission and Location of Hernia Surgery: A Matched Case-Control Study in the Veterans Administration. PMID- 27682222 TI - Characteristics of number transcoding errors of Chinese- versus English-speaking Alzheimer's disease patients. AB - Number processing disorder is an acquired deficit in mathematical skills commonly observed in Alzheimer's disease (AD), usually as a consequence of neurological dysfunction. Common impairments include syntactic errors (800012 instead of 8012) and intrusion errors (8 thousand and 12 instead of eight thousand and twelve) in number transcoding tasks. This study aimed to understand the characterization of AD-related number processing disorder within an alphabetic language (English) and ideographical language (Chinese), and to investigate the differences between alphabetic and ideographic language processing. Chinese-speaking AD patients were hypothesized to make significantly more intrusion errors than English-speaking ones, due to the ideographical nature of both Chinese characters and Arabic numbers. A simplified number transcoding test derived from EC301 battery was administered to AD patients. Chinese-speaking AD patients made significantly more intrusion errors (p = 0.001) than English speakers. This demonstrates that number processing in an alphabetic language such as English does not function in the same manner as in Chinese. The impaired inhibition capability likely contributes to such observations due to its competitive lexical representation in brain for Chinese speakers. PMID- 27682223 TI - Questionnaire-Based Development of an Educational Program of Traditional Japanese Kampo Medicine. AB - Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course's strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except "opportunities to learn about clinical cases" and "opportunities to practice involvement" were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study. PMID- 27682224 TI - Psychometric Properties of the Chinese Version of the Children's Resourcefulness Scale in Taiwanese Children. AB - This study reports the psychometric properties of a Chinese version of the Children's Resourcefulness Scale (C-CRS) for Taiwanese children. An instrument for assessing resourcefulness skills in children and adolescents, the CRS was translated into Mandarin Chinese, and a cross-sectional investigation was conducted with a convenience sample of 368 fifth and sixth graders recruited from three geographically diverse locations in Taiwan. Internal consistency statistics from the total sample and subgroups were between .57 and .71 with lower alphas for subgroups with disadvantaged socioeconomic status. Findings suggest that the C-CRS has the potential to assess children's resourcefulness skills in the Taiwanese population. PMID- 27682225 TI - Examining the specific dimensions of distress tolerance that prospectively predict perceived stress. AB - We examined five dimensions of distress tolerance (i.e. uncertainty, ambiguity, frustration, negative emotion, physical discomfort) as prospective predictors of perceived stress. Undergraduate students (N = 135) completed self-report questionnaires over the course of two assessment sessions (T1 and T2). Results of a linear regression in which the five dimensions of distress tolerance and covariates (i.e. T1 perceived stress, duration between T1 and T2) served as predictor variables and T2 perceived stress served as the outcome variable showed that intolerance of uncertainty was the only dimension of distress tolerance to predict T2 perceived stress. To better understand this prospective association, we conducted a post hoc analysis simultaneously regressing two subdimensions of intolerance of uncertainty on T2 perceived stress. The subdimension representing beliefs that "uncertainty has negative behavioral and self-referent implications" significantly predicted T2 perceived stress, while the subdimension indicating that "uncertainty is unfair and spoils everything" did not. Results support a growing body of research suggesting intolerance of uncertainty as a risk factor for a wide variety of maladaptive psychological outcomes. Clinical implications will be discussed. PMID- 27682226 TI - Iron Deficiency Anemia Coexists with Cancer Related Anemia and Adversely Impacts Quality of Life. AB - Cancer related anemia (CRA) adversely affects patient Quality of Life (QoL) and overall survival. We prospectively studied the prevalence, etiology and the impact of anemia on QoL in 218 Indian cancer patients attending a tertiary referral hospital. The study used the sTfR/log Ferritin index to detect iron deficiency anemia and assessed patient QoL using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) tool, standardized for language. Mean patient age was 51+/-13 years and 60% were female. The prevalence of cancer related anemia in this setting was 64% (n = 139). As expected, plasma ferritin did not differ significantly between anemic (n = 121) and non-anemic cancer patients (n = 73). In contrast, plasma sTfR levels were significantly higher in anemic cancer patients compared to non-anemic cancer patients (31 nmol/L vs. 24 nmol/L, p = 0.002). Among anemic cancer patients, using the sTfR/log Ferritin index, we found that 60% (n = 83) had iron deficiency anemia (IDA). Interestingly, plasma sTfR levels were significantly higher in cancer patients with CRA+IDA (n = 83) compared with patients having CRA (n = 38) alone (39 nmol/L vs. 20 nmol/L, p<0.001). There was a significant linear correlation between Hb and QoL (Spearman rho = 0.21; p = 0.001) and multivariate regression analysis revealed that every gram rise in Hb was accompanied by a 3.1 unit increase in the QoL score (95% CI = 0.19-5.33; p = 0.003). The high prevalence of anemia in cancer patients, a major portion of which is due to iron deficiency anemia, the availability of sensitive and specific biomarkers of iron status to detect IDA superimposed on anemia of inflammation, suggests an urgent need to diagnose and treat such patients. Despite the potential negative consequences of increasing metabolically available plasma iron in cancer, our clinical data suggest that detecting and treating IDA in anemic cancer patients will have important consequences to their QoL and overall survival. Clinical trials of iron therapy in these patients will be able to demonstrate the potential for benefit or harm. PMID- 27682228 TI - Ongoing increase in incidence and prevalence of multiple sclerosis in Newcastle, Australia: A 50-year study. AB - BACKGROUND: Since 1959, multiple sclerosis (MS) prevalence has been estimated for the east coast Australian city of Newcastle. Previous surveys, conducted in 1988 and 2003, have described an increase in the prevalence and incidence of MS. OBJECTIVES: In this study, we evaluated whether these trends continue and provide 50 years of MS epidemiological follow-up for this southern hemisphere city. METHODS: Expressed per 100,000 people, prevalence of MS in Newcastle was calculated for those with a confirmed diagnosis of MS on 9 August 2011 and incidence based on the number of cases with MS diagnosis made during the preceding decade. Data were age-standardised to the total Australian population. Statistical comparisons were undertaken using Poisson regression analysis. RESULTS: In 2011, the estimate of MS prevalence was 124.2, with female-to-male ratio reaching 3.1, a 53% increase in female predominance since 1996. MS incidence increased to 6.7, with a significantly higher proportion of new female cases since the previous survey. CONCLUSION: Prevalence of MS in Newcastle has risen linearly and is contributed to by a substantial increase in new cases over the preceding decade. Female predominance of MS cases continues to increase with a new diagnosis three times more likely in women. PMID- 27682227 TI - Baseline EDSS proportions in MS clinical trials affect the overall outcome and power: A cautionary note. AB - BACKGROUND: In randomized clinical trials, when treatments do not work equally effectively across stratifications of participants, observed event rates may differ from those hypothesized leading to deviations in estimated power. OBJECTIVES: To investigate the effect of distributions of baseline Expanded Disability Status Scale (EDSS) proportions in relapsing-remitting multiple sclerosis (RRMS) on the trial outcome, confirmed disability progression rate (CDPR), and power. METHODS: We reported CDPRs in the CombiRx trial by baseline EDSS and by groups (1st (0, 1), 2nd (1.5, 2), 3rd (2.5, 3), and 4th (?3.5)) and investigated the effect of different combinations of baseline EDSS proportions on the trial outcome and power. RESULTS: There were 244 (25.4%) participants in the 1st group, 368 (38.4%) in the 2nd group, 223 (23.3%) in the 3rd group, and 124 (12.9%) in the 4th group with CDPRs of 40.1%, 13.9%, 11.2%, and 16.9%, respectively. Both CDPR and power increased when the proportion of the 1st group increased in hypothetical trials with equal sample sizes in each arm, and a 10% increase in the 1st group led to a 5% increase in power. CONCLUSION: Various baseline EDSS proportions yielded different CDPRs and power, suggesting caution in interpretation of treatment effects across trials that enrolled participants with different proportions of baseline EDSS. PMID- 27682229 TI - Internet-based treatment for depression in multiple sclerosis: A randomized controlled trial. AB - BACKGROUND: Depression in multiple sclerosis (MS) patients is common but may stay untreated. Physical limitations impede face-to-face treatment. Internet-based treatment is therefore a promising tool for treating depression in MS. OBJECTIVES: To investigate effectiveness of a guided Internet-based problem solving treatment (IPST) for depressed MS patients. METHODS: MS patients with moderate or severe depressive symptoms were randomly assigned to IPST or a wait list control. Primary outcome was the change in depressive symptoms defined by a change in sum score on the Beck Depression Inventory Second Edition (BDI-II). Assessments took place at baseline (T0), within a week after the intervention (T1), and at 4 months follow-up (T2). Analyses were based on the intention-to treat principle. RESULTS: A total of 171 patients were randomized to IPST ( n = 85) or a wait list control ( n = 86). T1 was completed by 152 (89%) and T2 by 131 patients (77%). The IPST group and wait list control showed large significant improvements in depressive symptoms, but no differences were found between groups at T1 ( d = 0.23; 95% confidence interval (CI) = (-4.03, 1.08); p = 0.259) and T2 ( d = 0.01; 95% CI = (-2.80, 2.98); p = 0.953). CONCLUSION: We found no indication that IPST for MS patients with moderate or severe depression is effective in reducing depressive symptoms compared to a waiting list. Large improvements in the wait list control were unexpected and are discussed. PMID- 27682231 TI - Increased cerebrospinal fluid metalloproteinase-2 and interleukin-6 are associated with albumin quotient in neuromyelitis optica: Their possible role on blood-brain barrier disruption. AB - BACKGROUND: Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood-brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown. OBJECTIVE: We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO. METHODS: The concentrations 9 MMPs, 4 TIMPs, and 14 cytokines were measured by multiplex assay in CSF and serum samples from 29 NMO patients, 29 relapsing-remitting multiple sclerosis (MS) patients, and 27 patients with other neurological disorders. We also performed immunohistochemistry for MMP-2 and TIMP-1 expression in post-mortem brain tissues from NMO patients. RESULTS: NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF/serum albumin ratio, an index of BBB permeability, was most strongly correlated with CSF MMP-2 concentration, which in turn correlated with CSF interleukin-6 levels. Immunohistochemistry revealed MMP-2- and TIMP-1-positive cells surrounding vessels in NMO lesions. CONCLUSION: In NMO, increased CSF MMP-2, likely induced by interleukin-6 signaling, may disrupt the BBB and enable serum anti-AQP-4 antibodies migration into the central nervous system (CNS). PMID- 27682230 TI - Employment, disability pension and income for children with parental multiple sclerosis. AB - BACKGROUND: Little is known about the consequences of parental multiple sclerosis (MS) on offspring's socioeconomic circumstances. OBJECTIVE: To investigate employment, disability pension and income in offspring of parents with MS compared with matched reference persons in a nationwide register-based cohort study. METHODS: All Danish-born persons with onset of MS during 1950-1986 were retrieved from the Danish Multiple Sclerosis Registry. Their offspring were identified using the Civil Registration System. One random offspring from each sibship was matched by sex and year of birth with eight random reference persons. RESULTS: We included 2456 MS offspring and 19,648 reference persons. At age 30, employment was lower among MS offspring than reference children (odds ratio (OR): 0.89; 95% confidence interval (CI): 0.84-0.95; p = 0.0003), and they more often received disability pension (OR: 1.31; 95% CI: 1.15-1.50; p < 0.0001) at ages 30 and 40 but not at age 50. Although the mean income was not significantly lower for the MS offspring cohort, most of them attained an annual personal income below 250,000 DKK (Danish krone), that is, ~33,650 EUR (OR: 0.91; 95% CI: 0.84 0.99; p = 0.04). CONCLUSION: Having had a parent with MS may affect employment and increase the risk of disability pension and low income in adult life. PMID- 27682233 TI - The Science behind the Probiotic Strain Bifidobacterium animalis subsp. lactis BB 12((r)). AB - This review presents selected data on the probiotic strain Bifidobacterium animalis subsp. lactis BB-12((r)) (BB-12((r))), which is the world's most documented probiotic Bifidobacterium. It is described in more than 300 scientific publications out of which more than 130 are publications of human clinical studies. The complete genome sequence of BB-12((r)) has been determined and published. BB-12((r)) originates from Chr. Hansen's collection of dairy cultures and has high stability in foods and as freeze dried powders. Strain characteristics and mechanisms of BB-12((r)) have been established through extensive in vitro testing. BB-12((r)) exhibits excellent gastric acid and bile tolerance; it contains bile salt hydrolase, and has strong mucus adherence properties, all valuable probiotic characteristics. Pathogen inhibition, barrier function enhancement, and immune interactions are mechanisms that all have been demonstrated for BB-12((r)). BB-12((r)) has proven its beneficial health effect in numerous clinical studies within gastrointestinal health and immune function. Clinical studies have demonstrated survival of BB-12((r)) through the gastrointestinal tract and BB-12((r)) has been shown to support a healthy gastrointestinal microbiota. Furthermore, BB-12((r)) has been shown to improve bowel function, to have a protective effect against diarrhea, and to reduce side effects of antibiotic treatment, such as antibiotic-associated diarrhea. In terms of immune function, clinical studies have shown that BB-12((r)) increases the body's resistance to common respiratory infections as well as reduces the incidence of acute respiratory tract infections. PMID- 27682234 TI - Butyrolactone I Quantification from Lovastatin Producing Aspergillus terreus Using Tandem Mass Spectrometry-Evidence of Signalling Functions. AB - Aspergillus terreus is an industrially important filamentous fungus producing a wide spectrum of secondary metabolites, including lovastatin and itaconic acid. It also produces butyrolactone I which has shown potential as an antitumour agent. Additionally, butyrolactone I has been implicated to have a regulating role in the secondary metabolism and morphology of A. terreus. In this study, a quantitative time-course liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS-MS) analysis of butyrolactone I is reported for the first time in nine-day long submerged cultures of A. terreus. Butyrolactone I was fragmented in the mass analysis producing a reproducible fragmentation pattern of four main daughter ions (m/z 307, 331, 363 and 393) in all the samples tested. Supplementing the cultures with 100 nM butyrolactone I caused a statistically significant increase (up to two-fold) in its production, regardless of the growth stage but was constitutive when butyrolactone I was added at high cell density during the stationary phase. Furthermore, the extracellular butyrolactone I concentration peaked at 48 h post inoculation, showing a similar profile as has been reported for bacterial quorum sensing molecules. Taken together, the results support the idea of butyrolactone I as a quorum sensing molecule in A. terreus. PMID- 27682232 TI - Relationship between Body Composition and Pulmonary Function in Early Adult Life: A Cross-Sectional Analysis Nested in Two Birth Cohort Studies. AB - BACKGROUND: Overweight/obesity has been reported to worsen pulmonary function (PF). This study aimed to examine the association between PF and several body composition (BC) measures in two population-based cohorts. METHODS: We performed a cross-sectional analysis of individuals aged 18 and 30 years from two Pelotas Birth Cohorts in southern Brazil. PF was assessed by spirometry. Body measures that were collected included body mass index, waist circumference, skinfold thickness, percentages of total and segmented (trunk, arms and legs) fat mass (FM) and total fat-free mass (FFM). FM and FFM were measured by air-displacement plethysmography (BODPOD) and by dual-energy x-ray absorptiometry (DXA). Associations were verified through linear regressions stratified by sex, and adjusted for weight, height, skin color, and socioeconomic, behavioral, and perinatal variables. RESULTS: A total of 7347 individuals were included in the analyses (3438 and 3909 at 30 and 18 years, respectively). Most BC measures showed a significant positive association between PF and FFM, and a negative association with FM. For each additional percentage point of FM, measured by BOD POD, the forced vital capacity regression coefficient adjusted by height, weight and skin color, at 18 years, was -33 mL (95% CI -38, -29) and -26 mL (95% CI -30, -22), and -30 mL (95% CI -35, -25) and -19 mL (95% CI -23, -14) at 30 years, in men and women, respectively. All the BOD POD regression coefficients for FFM were the same as for the FM coefficients, but in a positive trend (p<0.001 for all associations). CONCLUSIONS: All measures that distinguish FM from FFM (skinfold thickness-FM estimation-BOD POD, total and segmental DXA measures-FM and FFM proportions) showed negative trends in the association of FM with PF for both ages and sexes. On the other hand, FFM showed a positive association with PF. PMID- 27682235 TI - Microorganisms-A Journal and a Unifying Concept for the Science of Microbiology. AB - The MDPI journal Microorganisms is still very young, having been launched in 2013, but the concept of the microorganism has been in use for at least a century as a unifying principle for the discipline of microbiology, which was cemented firmly by the intellectual work of Roger Stanier and colleagues in their Microbial World and other general microbiology textbooks and related articles from the 1950s to the 1970s [1,2]. Merging the idea of the microscopic and the very small with the older idea of an organism as a living entity or cell, the concept of a microorganism enabled a real appreciation of the microbial world as one that is amenable to study using similar tools and approaches even though representing distinctly different types of reproductive units and cell organizations. In the late 20th century following the work of Carl Woese and other molecular evolutionists, biologists came to appreciate the commonality among all organisms, all being comprised of cells that bear a remarkable similarity to one another and that share a common evolutionary ancestry, and consequently with major features of a largely shared genetic code and molecular biology. In this sense microbiology and biology as a whole became unified as they never had been before.[...]. PMID- 27682237 TI - Understanding how dogs encourage and motivate walking: cross-sectional findings from RESIDE. AB - BACKGROUND: Many people live with dogs but not all walk with them regularly. This study examines the demographic and behavioural factors that contribute towards owners reporting having a strong sense of encouragement and motivation to walk provided by their dogs, which we call 'the Lassie effect'. METHODS: Data was collected from 629 dog owners participating in the RESIDE cross-sectional survey in Perth, Western Australia. Multivariable logistic regression analyses of factors associated with two separate outcome survey items 'Dog encouragement to walk' (how often dog encouraged me to go walking in last month) and 'Dog motivation to walk' (Having a dog makes me walk more). RESULTS: Owning a larger dog; having an increased level of attachment to dog; knowing dog enjoys going for a walk; believing walking keeps dog healthy; and having high social support from family to go walking, were positively associated with both outcomes 'dog encouragement to walk' and 'dog motivation to walk'. Conversely, reporting the presence of children at home; that the child is the main person who walks with the dog; and perceiving dog-specific barriers to walking with dog daily; were negatively associated with both outcomes. In addition, 'Dog motivation to walk' only was positively associated with a belief walking reduces barking, and negatively with owning a dog that is overweight or a dog that is too old/sick. Reporting that the spouse/partner is main person who walks with the dog was also negatively associated with 'dog motivation to walk', as was increased perceived access to public open spaces with dog-supportive features. CONCLUSIONS: There are both dog and owner factors that are associated with an owner's sense of encouragement, and motivation to walk the dog, which in turn has been found to be associated with dog waking behaviour. These factors may be targeted in future interventions to increase and maintain physical activity levels of both people and pets. PMID- 27682238 TI - Serial Native T1 Mapping to Monitor Cardiac Response to Treatment in Light-Chain Amyloidosis. PMID- 27682236 TI - Implementing goals of care conversations with veterans in VA long-term care setting: a mixed methods protocol. AB - BACKGROUND: The program "Implementing Goals of Care Conversations with Veterans in VA LTC Settings" is proposed in partnership with the US Veterans Health Administration (VA) National Center for Ethics in Health Care and the Geriatrics and Extended Care Program Offices, together with the VA Office of Nursing Services. The three projects in this program are designed to support a new system wide mandate requiring providers to conduct and systematically record conversations with veterans about their preferences for care, particularly life sustaining treatments. These treatments include cardiac resuscitation, mechanical ventilation, and other forms of life support. However, veteran preferences for care go beyond whether or not they receive life-sustaining treatments to include issues such as whether or not they want to be hospitalized if they are acutely ill, and what kinds of comfort care they would like to receive. METHODS: Three projects, all focused on improving the provision of veteran-centered care, are proposed. The projects will be conducted in Community Living Centers (VA-owned nursing homes) and VA Home-Based Primary Care programs in five regional networks in the Veterans Health Administration. In all the projects, we will use data from context and barrier and facilitator assessments to design feedback reports for staff to help them understand how well they are meeting the requirement to have conversations with veterans about their preferences and to document them appropriately. We will also use learning collaboratives-meetings in which staff teams come together and problem-solve issues they encounter in how to get veterans' preferences expressed and documented, and acted on-to support action planning to improve performance. DISCUSSION: We will use data over time to track implementation success, measured as the proportions of veterans in Community Living Centers (CLCs) and Home-Based Primary Care (HBPC) who have a documented goals of care conversation soon after admission. We will work with our operational partners to spread approaches that work throughout the Veterans Health Administration. PMID- 27682239 TI - 1 H and 13 C NMR spectral assignments of flavone derivatives. PMID- 27682240 TI - Reward: Calculating error. PMID- 27682241 TI - Extraction of hermit crabs from their shells by white-faced capuchin monkeys (Cebus capucinus). AB - We observed two capuchin monkeys (Cebus capucinus) feeding on hermit crabs (Coenobita compressus) on the coast, and the tactics they used to extract this well-protected prey. The observations took place during the dry season at Playa Escondida beach, Puntarenas, Costa Rica. The capuchins descended from trees at the back edge of the beach to capture passing hermit crabs. Both capuchins extracted the hermit crabs from their protective shells by holding the shell with one hand and pulling the crab out with the other. Even though this was accomplished within seconds, the extraction of hermit crabs from their shells did not appear to be a straightforward task. Once the capuchins succeeded in pulling the crabs out of their shells, they consumed the soft abdomen and discarded the rest of the crab's body. To our knowledge, the consumption of hermit crabs has not been previously reported for any capuchin monkey (Cebus or Sapajus). Our observations provide a new example of extractive foraging by capuchins, and thus an additional natural context for which fine motor skills (which are highly developed in capuchins) are necessary. PMID- 27682242 TI - Dietary Patterns for Women With Triple-negative Breast Cancer and Dense Breasts. AB - Triple-negative breast cancer (TNBC) is a common subtype of breast cancer among women with dense breasts and is associated with a poor prognosis. Diet is a modifiable risk factor for breast cancer, but the association between the risk of TNBC and diet has not been studied. The present study investigated the hypothesis that a healthy dietary pattern was negatively associated with risk of TNBC in women with dense breasts (density types 3 and 4). After total mastectomy or breast conserving surgery, patients with TNBC (n = 38) and non-TNBC (n = 178) were recruited. The risk of TNBC was negatively associated with a healthy dietary pattern involving consumption of seafood and vegetables, and positively associated with a dietary pattern of consuming grains, meats, and eggs. Additionally, intake of animal fat, eggs, and meat was positively associated with the risk of TNBC, but intake of vegetable fats, nuts, and vegetables showed a negative association. Patients with TNBC had higher proportion of obesity or abdominal obesity than those with non-TNBC. The present study is the first to show a negative association between risk of TNBC and a healthy dietary pattern in women with dense breasts and suggests the importance of diet in the prevention of TNBC. PMID- 27682243 TI - Health services utilization in patients with eating disorders: evidence from a cohort study in Emilia-Romagna. AB - PURPOSE: To estimate the treated prevalence of eating disorders (ED) in Emilia Romagna, Italy, and to compare health services utilization among age groups and geographical areas. METHODS: The study cohort consists of patients aged 12-64 years with a primary or secondary ED diagnosis, treated in regional healthcare facilities in 2012. Patients were followed up for 1 year from the first contact. Data were extracted from regional administrative databases. RESULTS: The study cohort included 1550 cases, 36.8 % with anorexia nervosa, 21.9 % with bulimia nervosa and 41.3 % with ED not otherwise specified. Adolescents (12-17 years) were 18.6 %, young adults (18-30) 32.7 % and older adults (31-64) 48.7 %. The annual treated prevalence rate was 5.2/10,000 (13.3 for adolescents, 9.3 for young adults and 3.4 for older adults) and was highest among adolescent (24.6/10,000) and young adult females (17.1/10,000). Cases without a record for ED in the previous year were 46.8 %. Older adults displayed higher comorbidity and used more services including hospital-based care. Outpatient care greatly exceeded inpatient care across age groups. Variations in care patterns across regional areas were found. CONCLUSIONS: Our results indicate that the care pathway for ED varies among age groups and geographical areas, but is consistent with the regional care model that favors the use of outpatient services. Future perspectives include evaluating the integration among mental health services, specialty outpatient units and primary care. PMID- 27682244 TI - Regulation of aPKC activity by Nup358 dependent SUMO modification. AB - Atypical PKC (aPKC) family members are involved in regulation of diverse cellular processes, including cell polarization. aPKCs are known to be activated by phosphorylation of specific threonine residues in the activation loop and turn motif. They can also be stimulated by interaction with Cdc42~GTP-Par6 complex. Here we report that PKCzeta, a member of the aPKC family, is activated by SUMOylation. We show that aPKC is endogenously modified by SUMO1 and the nucleoporin Nup358 acts as its SUMO E3 ligase. Results from in vitro SUMOylation and kinase assays showed that the modification enhances the kinase activity of PKCzeta by ~10-fold. By monitoring the phosphorylation of Lethal giant larvae (Lgl), a downstream target of aPKC, we confirmed these findings in vivo. Consistent with the function of Nup358 as a SUMO E3 ligase for aPKC, depletion of Nup358 attenuated the extent of SUMOylation and the activity of aPKC. Moreover, overexpression of the C-terminal fragment of Nup358 that possesses the E3 ligase activity enhanced SUMOylation of endogenous aPKC and its kinase activity. Collectively, our studies reveal a role for Nup358-dependent SUMOylation in the regulation of aPKC activity and provide a framework for understanding the role of Nup358 in cell polarity. PMID- 27682248 TI - Hypocalcaemia after denosumab in older people following fracture. AB - : Hypocalcaemia following denosumab therapy can be observed in older adults. This is more common if their pre-treatment corrected serum calcium concentrations are less than 2.28 mmol/L. Denosumab remains a safe treatment in older people but we recommend a cautious approach in people at risk. INTRODUCTION: Previous studies have indicated that denosumab, an anti-RANK ligand (RANKL) monoclonal antibody, for treatment of osteoporosis is well-tolerated. There is little data specifically regarding its adverse effect profile in a hospitalised older person. Primarily, this study wished to determine the frequency of hypocalcaemia following denosumab administration in older people admitted to hospital following fracture. Secondarily, this study wished to determine any associations that may predict the development of hypocalcaemia. METHODS: This was a prospective study of 33 participants using a paired study design aged 70 years old or more with fragility fractures who were given denosumab in a rehabilitation hospital in Sydney. The primary outcome was the frequency of hypocalcaemia. Hypocalcaemia was defined as corrected serum concentration of less than 2.20 mmol/L on day 14 after denosumab administration. RESULTS: Of the 33 participants with a mean age of 84.6 +/- 1.2 years old, 5 participants (15.2 %) developed hypocalcaemia post injection. A paired t test showed a mean difference between the baseline and post injection calcium concentrations to be 0.059 mmol/L (95 %CI 0.020-0.098; t = 3.080, p = 0.004). Regression analysis showed that pre-denosumab serum calcium concentration correlated with the post-denosumab injection calcium concentration (R = 0.631, 95 %CI 0.288-0.977; p = 0.001). No other variables were significant. Further, a baseline serum calcium concentration of 2.28 mmol/L was able to predict post-denosumab hypocalcaemia with a sensitivity of 80 % and specificity of 86 %. CONCLUSIONS: Denosumab is a relatively safe treatment of osteoporosis. This study shows that hypocalcaemia following denosumab therapy can be observed in older adults. Clinicians should be aware of this adverse effect when using denosumab in the older people. PMID- 27682250 TI - Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib. AB - Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy. In this report, we describe a sustained response of an unresectable multifocal form of adult medulloblastoma to vismodegib. Molecular analysis in this case revealed mutations in TP53 and a cytogenetic abnormality, i17q, that is prevalent and most often associated with subgroup 4 rather than the SHH-activated form of medulloblastoma. Our findings indicate that vismodegib may also block alternate, non-canonical forms of downstream SHH pathway activation. These findings provide strong impetus for further investigation of vismodegib in clinical trials in the first-line setting for pediatric and adult forms of medulloblastoma. PMID- 27682249 TI - Higher serum sclerostin levels and insufficiency of vitamin D are strongly associated with vertebral fractures in hemodialysis patients: a case control study. AB - : In hemodialysis patients, vertebral fractures were associated with elevated sclerostin levels, suggesting that sclerostin could reflect bone fragility in these patients. INTRODUCTION: Fragility fractures are common in hemodialysis patients. The aims of our study were to determine the prevalence of vertebral fracture and analyze associations between sclerostin serum levels and vertebral fractures in hemodialysis patients. METHODS: Ninety-two hemodialysis patients and 100 controls matched for age and sex were studied. Bone mineral density was measured by ultrasonography at non-dominant heel. The markers of bone turnover included serum osteocalcin, C-terminal telopeptide, and sclerostin. All participants underwent radiography of the thoracic and lumbar spine to ascertain the presence of vertebral fractures. RESULTS: Bone ultrasound parameters at calcaneus were significantly lower in hemodialysis patients compared with controls; bone turnover markers and parathyroid hormone level were significantly higher, while serum of 25-OH-D3 was significantly lower in hemodialysis group. One or more moderate or severe vertebral fractures were found in 38 hemodialysis patients, whereas in control group, 10 patients had a vertebral fracture. In hemodialysis group, the comparison between patients with and without vertebral fractures showed that the patients with vertebral fractures had the serum sclerostin levels statistically higher than patients without vertebral, while serum levels of 25-OH-D3 was significantly lower in patients with vertebral fractures compared to the patients without vertebral fractures. Multivariate analysis disclosed that sclerostin levels were associated with an increased risk of vertebral fractures in hemodialysis patients after adjusting for multiple variables. CONCLUSIONS: Our data shows high prevalence of vertebral fractures in hemodialysis patients and that it is associated with elevated sclerostin levels, reflecting bone fragility in these patients. PMID- 27682251 TI - The impact of healthcare visit timing on reported pertussis cough duration: Selection bias and disease pattern from reported cases in Michigan, USA, 2000 2010. AB - BACKGROUND: Pertussis is a potentially serious respiratory illness characterized by cough of exceptionally long duration of up to approximately100 days. While macrolide antibiotics are an effective treatment, there is an ongoing debate whether they also shorten the length of cough symptoms. We investigated whether public health surveillance data for pertussis, in which cases are identified at diagnosis, are potentially affected by selection bias and the possible consequences for reported cough duration. METHODS: Data on 4,794 pertussis cases reported during 2000-2010 were extracted from the Michigan Disease Surveillance System, a statewide, web-based communicable disease reporting system, to specifically investigate increased duration of cough observed in pertussis patients with delayed initial healthcare visit. A simulated population of cases was derived from the observed surveillance data and truncated week-by-week to evaluate the effects of bias associated with stratification on timing of antibiotics. RESULTS: Cases presenting for medical evaluation later in the clinical course were more likely to have experienced delayed antibiotic therapy and longer average cough duration. A comparable magnitude of increasing cough duration was also observed in the simulated data. By stratifying on initial medical visit, selection bias effects based on timing of healthcare visit were demonstrated. CONCLUSIONS: Stratifying or controlling for the timing of the initial case identification and accompanying antibiotic treatment can create artificial patterns of observed cough duration. In surveillance data, differences in symptom duration may arise from selection bias and should not be presumed to be related to early antibiotic treatment. PMID- 27682252 TI - Expansion and Contraction of the Indo-Pacific Tropical Rain Belt over the Last Three Millennia. AB - The seasonal north-south migration of the intertropical convergence zone (ITCZ) defines the tropical rain belt (TRB), a region of enormous terrestrial and marine biodiversity and home to 40% of people on Earth. The TRB is dynamic and has been shown to shift south as a coherent system during periods of Northern Hemisphere cooling. However, recent studies of Indo-Pacific hydroclimate suggest that during the Little Ice Age (LIA; AD 1400-1850), the TRB in this region contracted rather than being displaced uniformly southward. This behaviour is not well understood, particularly during climatic fluctuations less pronounced than those of the LIA, the largest centennial-scale cool period of the last millennium. Here we show that the Indo-Pacific TRB expanded and contracted numerous times over multi decadal to centennial scales during the last 3,000 yr. By integrating precisely dated stalagmite records of tropical hydroclimate from southern China with a newly enhanced stalagmite time series from northern Australia, our study reveals a previously unidentified coherence between the austral and boreal summer monsoon. State-of-the-art climate model simulations of the last millennium suggest these are linked to changes in the structure of the regional manifestation of the atmosphere's meridional circulation. PMID- 27682253 TI - Studies on forensic nursing in Brazil: a systematic review of the literature. AB - AIM: To identify and synthesize the national and international literature on forensic nursing in Brazil. BACKGROUND: Forensic nursing is a new specialty to the nursing practice in Brazil, being recognized by the Federal Nursing Council of Brazil in 2011. In 2016, the first forensic nursing specialization programme was authorized in the country. INTRODUCTION: The implementation of forensic nursing specialty in Brazil marks new possibilities for the nursing practice, making it possible for nurses to develop additional skills to intervene in various situations under the Brazilian Unified Healthcare System. METHODS: A systematic search of the literature was conducted using the keyword 'Forensic nursing' in combination with 'Brazil'. LILACS, MEDLINE, EMBASE, Scopus and Web of Science databases were searched. Studies were also retrieved from the grey literature. Once literature had been identified, a thematic analysis was undertaken in order to extract themes, which were: establishment of the forensic nursing specialty and its contributions to Brazil and its practical implications. RESULTS: Eight manuscripts and 20 studies from the grey literature were included in the final review. Most studies (54%) were literature reviews that indicated forensic nursing as an emerging specialty in Brazil, addressing educational, instructional, communicative or contextual aspects of the specialty in the country. DISCUSSION: In the nursing profession in Brazil, few studies exist on forensic nursing and those are limited to short communications. Although most studies address the definition of forensic nursing, others present its implications in various situations such as intimate partner violence, domestic violence, sexual abuse and elder mistreatment. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Despite the study limitations, it provides evidence that forensic nursing has been silently implemented in the country with the need for more evidence-based studies to support its constitution as a specialty in Brazil. PMID- 27682255 TI - The burgeoning field of innate immune-mediated disease and autoinflammation. AB - Immune-mediated autoinflammatory diseases are occupying an increasingly prominent position among the pantheon of debilitating conditions that afflict humankind. This review focuses on some of the key developments that have occurred since the original description of autoinflammatory disease in 1999, and focuses on underlying mechanisms that trigger autoinflammation. The monogenic autoinflammatory disease range has expanded considerably during that time, and now includes a broad spectrum of disorders, including relatively common conditions such as cystic fibrosis and subsets of systemic lupus erythematosus. The innate immune system also plays a key role in the pathogenesis of complex inflammatory disorders. We have proposed a new nomenclature to accommodate the rapidly increasing number of monogenic disorders, which predispose to either autoinflammation or autoimmunity or, indeed, combinations of both. This new terminology also encompasses a wide spectrum of genetically determined autoinflammatory diseases, with variable clinical manifestations of immunodeficiency and immune dysregulation/autoimmunity. We also explore some of the ramifications of the breakthrough discovery of the physiological role of pyrin and the search for identifiable factors that may serve to trigger attacks of autoinflammation. The evidence that pyrin, as part of the pyrin inflammasome, acts as a sensor of different inactivating bacterial modification Rho GTPases, rather than interacting directly with these microbial products, sets the stage for a better understanding of the role of microorganisms and infections in the autoinflammatory disorders. Finally, we discuss some of the triggers of autoinflammation as well as potential therapeutic interventions aimed at enhancing autophagy and proteasome degradation pathways. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27682257 TI - On Dioxygen and Substrate Access to Soluble Methane Monooxygenases: An all-Atom Molecular Dynamics Investigation in Water Solution. AB - In a preliminary exploration of the dummy model for diiron proteins, random acceleration molecular dynamics (RAMD) revealed that a pure four-helix bundle structure, like hemerythrin, constitutes an efficient cage for dioxygen (O2 ), which can only leave from defined, albeit very broad, gates. However, this well ordered structure does not constitute an archetype on which to compare O2 permeation of other diiron proteins, like the complex of soluble methane monooxygenase hydroxylase with the regulatory protein (sMMOH-MMOB). The reason is that with this complex, unlike hemerythrin, the four helices of the four-helix bundle are heavily bent, and RAMD showed that most traps for O2 lie outside them. It was also observed that, in spite of a nearly identical van der Waals radius for O2 and the natural substrate CH4 , the latter behaves under RAMD as a bulkier molecule than O2 , requiring a higher external force to be brought out of sMMOH MMOB along trajectories of viable length. All that determined with sMMOH-MMOB multiple gates and multiple pathways to each of them through several binding pockets, for both O2 and CH4 . Of the two equally preferred pathways for O2 , at right angle with one another, one proved to be in accordance with the Xe-atom mapping for sMMOH. In contrast, none of the pathways identified for CH4 proved to be in accordance with such mapping, CH4 looking for more open avenues instead. PMID- 27682258 TI - Number of Grooming Partners Is Associated with Hookworm Infection in Wild Vervet Monkeys (Chlorocebus aethiops). AB - There are many known benefits of social grooming among primates, including maintenance of social relationships, removal of ectoparasites, and improved physiological condition. Recently, however, researchers have noted that social grooming and social contact may also present a significant cost by facilitating transmission of some parasites and pathogens. We investigated whether the number of social grooming partners varied based on infection status for gastrointestinal parasites. We used focal animal sampling and continuous recording to collect data on the number of grooming partners for known individual vervet monkeys (Chlorocebus aethiops). We collected non-invasive faecal samples and examined them using faecal flotation, faecal sedimentation, and immunofluorescence microscopy. We detected 6 parasites: Trichuris sp. (92%), hookworm (71%), spirurids (68%), Oesophagostomum sp. (84%), Strongyloides sp. (24%), and Entamoeba coli (92%). The number of grooming partners varied significantly based on infection with hookworm and sex. No significant relationships were detected for other parasites. Associations between host behavioural variation and some parasite taxa (specifically Trichuris, Oesophagostomum, and Entamoeba spp.) were impossible to explore due to an extremely high prevalence among hosts. This is the first report that we are aware of that has detected an association between social grooming behaviours and infection with hookworm. PMID- 27682259 TI - Medical students' perceptions towards research at a Sudanese University. AB - BACKGROUND: Inadequately designed curricula and barriers to research have not enabled students to realize the crucial importance of research to clinical practice. Several studies have reported variable results with regards to research training. The aim of this survey was to evaluate research training at a university in Sudan which had provided research training for 17 years. METHODS: A university-based survey design, using a self-administered questionnaire, was conducted among final year medical students who completed 2 years of research training. Descriptive frequency analysis and bivariate analysis were performed using IBM SPSS version 20. RESULTS: The response rate was 76 %. Ninety-five (91.3 %) perceived research important to medicine and 62 (59.6 %) perceived that it should be a requirement for partial fulfillment of the MBBS degree. Elevation of professional standing as a clinician was the prime reason for pursuing a career in research (18/68.2 %). Main reasons for not pursuing a career in research was research being time consuming (49/59.8 %) and focusing on clinical service being more important than clinical research (48/58.5 %). Fifty-five (56.1 %) believe that their supervisor gave them a positive attitude to research. Principle barriers to student research were lack of funding (75/72.1 %), insufficient time (71/68.3 %) and the demands of the curriculum (70/67.3 %). No significant differences were detected between gender and perceptions towards research. CONCLUSION: The curriculum should be revised to address the gaps in research training. A small group learning model should be adopted to train students in research and provide supervision to group research projects. This model would improve academic learning, skills acquisition, encourage student interest in research, reduce barriers to student research and make better use of limited resources. PMID- 27682256 TI - Impact of Heat Stress on Cellular and Transcriptional Adaptation of Mammary Epithelial Cells in Riverine Buffalo (Bubalus Bubalis). AB - The present study aims to identify the heat responsive genes and biological pathways in heat stressed buffalo mammary epithelial cells (MECs). The primary mammary epithelial cells of riverine buffalo were exposed to thermal stress at 42 degrees C for one hour. The cells were subsequently allowed to recover at 37 degrees C and harvested at different time intervals (30 min to 48 h) along with control samples (un-stressed). In order to assess the impact of heat stress in buffalo MECs, several in-vitro cellular parameters (lactate dehydrogenase activity, cell proliferation assay, cellular viability, cell death and apoptosis) and transcriptional studies were conducted. The heat stress resulted in overall decrease in cell viability and cell proliferation of MECs while induction of cellular apoptosis and necrosis. The transcriptomic profile of heat stressed MECs was generated using Agilent 44 K bovine oligonucleotide array and at cutoff criteria of >=3-or <=3 fold change, a total of 153 genes were observed to be upregulated while 8 genes were down regulated across all time points post heat stress. The genes that were specifically up-regulated or down-regulated were identified as heat responsive genes. The upregulated genes in heat stressed MECs belonged to heat shock family viz., HSPA6, HSPB8, DNAJB2, HSPA1A. Along with HSPs, genes like BOLA, MRPL55, PFKFB3, PSMC2, ENDODD1, ARID5A, and SENP3 were also upregulated. Microarray data revealed that the heat responsive genes belonged to different functional classes viz., chaperons; immune responsive; cell proliferation and metabolism related. Gene ontology analysis revealed enrichment of several biological processes like; cellular process, metabolic process, response to stimulus, biological regulation, immune system processes and signaling. The transcriptome analysis data was further validated by RT-qPCR studies. Several HSP (HSP40, HSP60, HSP70, HSP90, and HSPB1), apoptotic (Bax and Bcl2), immune (IL6, TNFalpha and NF-kbeta) and oxidative stress (GPX1 and DUSP1) related genes showed differential expression profile at different time points post heat stress. The transcriptional data strongly indicated the induction of survival/apoptotic mechanism in heat stressed buffalo MECs. The overrepresented pathways across all time points were; electron transport chain, cytochrome P450, apoptosis, MAPK, FAS and stress induction of HSP regulation, delta Notch signaling, apoptosis modulation by HSP70, EGFR1 signaling, cytokines and inflammatory response, oxidative stress, TNF-alpha and NF- kB signaling pathway. The study thus identified several genes from different functional classes and biological pathways that could be termed as heat responsive in buffalo MEC. The responsiveness of buffalo MECs to heat stress in the present study clearly suggested its suitability as a model to understand the modulation of buffalo mammary gland expression signature in response to environmental heat load. PMID- 27682260 TI - Open-angle glaucoma and Alzheimer's disease: a population-based 30-year follow-up study. PMID- 27682261 TI - CONSIDER - Core Outcome Set in IAD Research: study protocol for establishing a core set of outcomes and measurements in incontinence-associated dermatitis research. AB - AIM: This study protocol describes the methodology for the development of a core set of outcomes and a core set of measurements for incontinence-associated dermatitis. BACKGROUND: Incontinence is a widespread disorder with an important impact on quality of life. One of the most common complications is incontinence associated dermatitis, resulting from chemical and physical irritation of the skin barrier, triggering inflammation and skin damage. Managing incontinence associated dermatitis is an important challenge for nurses. Several interventions have been assessed in clinical trials, but heterogeneity in study outcomes complicates the comparability and standardization. To overcome this challenge, the development of a core outcome set, a minimum set of outcomes and measurements to be assessed in clinical research, is needed. DESIGN: A project team, International Steering Committee and panelists will be involved to guide the development of the core outcome set. The framework of the Harmonizing Outcomes Measures for Eczema roadmap endorsed by Cochrane Skin Group Core Outcomes Set Initiative, is used to inform the project design. METHODS: A systematic literature review, interviews to integrate the patients' perspective and a consensus study with healthcare researchers and providers using the Delphi procedure will be performed. The project was approved by the Ethics review Committee (April 2016). DISCUSSION: This is the first project that will identify a core outcome set of outcomes and measurements for incontinence-associated dermatitis research. A core outcome set will reduce possible reporting bias, allow results comparisons and statistical pooling across trials and strengthen evidence-based practice and decision-making. REGISTRATION: This project has been registered in the Core Outcome Measures in Effectiveness Trials (COMET) database and is part of the Cochrane Skin Group Core Outcomes Set Initiative (CSG-COUSIN). PMID- 27682262 TI - Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis. AB - BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. METHODS: We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status. RT-qPCR was applied in four selected genes (B4GALT1, BAG1, PKD1L2, and PPP2R5A) covered by rare alterations, also including three MA and four normal oral tissues. RESULTS: Fifty seven CNAs and cnLOH were observed in the ameloblastomas and six CNAs in the AC. Seven of the CNAs were rare (six in UA and one in MA), four of them encompassing genes (gains of 7q11.21, 1q32.3, and 9p21.1 and loss of 16q23.2). We found positive correlation between rare CNA gene dosage and the expression of B4GALT1, BAG1, PKD1L2, and PPP2R5A. The AC and 1 UA were BRAF wild-type; however, this UA showed rare genomic alterations encompassing genes associated with RAF/MAPK activation. CONCLUSION: Ameloblastomas show rare CNAs and cnLOH, presenting a specific genomic profile with no overlapping of the rare alterations among UA, MA, and AC. These genomic changes might play a role in tumor evolution and in BRAFV600E-negative tumors. PMID- 27682264 TI - Intraoperative neuromonitoring in thyroidectomy: the learning curve. AB - AIM: To evaluate the learning curve in the use of intraoperative neuromonitoring of recurrent laryngeal nerve and vagus in thyroid surgery. MATERIALS OF THE STUDY: We analyzed 140 pts treated consecutively for thyroid disease. All the patients were neuromonitored with Intraoperative neuromonitoring of recurrent laryngeal nerve and vagus. We divided these patients in 7 groups to collect the adverse events during our learning curve. RESULTS: We monitored consecutively 271 nerves. The incidence of transient paralysis was 0.73%.No significant differences were recorded in the groups about the calceium values,the mean operative time. Sensitivity was 100%, specificity 99%, Predictive positive value was 33%, negative predictive value was 100%. DISCUSSION: The recurrent laryngeal nerve injury is the most frequent adverse event in thyroid surgery. The causes of the lesion are different. The introduction of non-invasive monitoring devices that define the standard of IONM in thyroidectomy is increasing in the last period. In our study we performed the neuromonitoring in four times finding several benefits: avoid damage from excessive traction of the thyroid; early identification of RLN extra-laryngeal branches; identification and preservation of the parathyroid glands. CONCLUSION: The use of neuromonitoring in course of thyroidectomy helps the surgeon to early localization, identification, visualization and dissection of the RLN. It is important highlight that for the surgeon, especially the less experienced, the opportunity to immediately verify the absence of nerve structures and the presence of lesions is very important especially in education and research. We confirm that real learning curve requires at least 60 consecutive cases as reported by others in literature. KEY WORDS: Hypocalcaemia, Intraoperative neuromonitoring, Learning curve, Recurrent laryngeal nerve injury, Thyroid surgery. PMID- 27682265 TI - Biomaterial microarchitecture: a potent regulator of individual cell behavior and multicellular organization. AB - Insoluble cues from a cell's surrounding microenvironment have increasingly been shown to be important regulators of cell behavior. The microarchitecture of biomaterials used for 3D cell encapsulation, however, is often underappreciated as an important insoluble factor guiding cell activity. In this review, we illustrate that the subcellular physical features of a scaffold influence a range of cell behaviors, including morphology, cytoskeletal organization, migration, matrix remodeling, and long-range force transmission. We emphasize that the microarchitecture of stromal extracellular matrix (ECM)-specifically the fact that it consists of a network of long interconnecting fibers with micron and nanometer-sized diameters-is an important determinant of how cells naturally interact with their surrounding matrix and each other. Synthetic biomaterials with a microarchitecture similar to stromal ECM can support analogous cellular responses, suggesting that this fibrous microarchitecture is a key regulator of these cell behaviors. Drawing upon examples from in vitro, in silico, and in vivo studies, we compare these behaviors in fibrous matrices to those of cells cultured within nanoporous matrices (e.g., alginate and PEG gels) as well as macroporous scaffolds to highlight key differences in the cellular response to each type of microarchitecture. Understanding how microarchitecture affects cell behavior can lead to more efficient biomaterial selection when designing tissue engineered scaffolds for therapeutic applications. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 640-661, 2017. PMID- 27682266 TI - Amiloride modifies the progression of lithium-induced renal interstitial fibrosis. AB - AIM: Long-term administration of lithium has been associated with the development of a chronic interstitial fibrosis in addition to nephrogenic diabetes insipidus (NDI). Earlier studies have demonstrated that amiloride, by blocking the epithelial sodium channel ENaC and thus preventing lithium uptake into the principal cells of the collecting ducts, can partially reverse lithium-induced NDI. However, there are no long-term studies examining whether or not amiloride also modifies the progressive chronic interstitial fibrosis and tubular atrophy often evident with long-term lithium exposure. METHODS: Using an established animal model of lithium-induced chronic interstitial fibrosis, rats were treated with amiloride and lithium for 5 months following 1 month of exposure to lithium alone and compared with control animals and those given only lithium. RESULTS AND CONCLUSIONS: In this study, the 5 months of amiloride therapy partially mitigated the lithium-induced NDI and limited the further progression of lithium-induced kidney fibrosis. This improvement was associated with decreased expression of the pro-fibrotic connective tissue growth factor (CTGF), along with reduced myofibroblast infiltration and decreased collagen deposition around the distended cortical collecting ducts. This may, in part, be mediated by modifying lithium induced alterations in beta-catenin activity through its effects on GSK-3beta. PMID- 27682263 TI - Bioavailable Trace Metals in Neurological Diseases. AB - OPINION STATEMENT: Medical treatment in Wilson's disease includes chelators (D penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators' doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron. PMID- 27682268 TI - Quantized conductance doubling and hard gap in a two-dimensional semiconductor superconductor heterostructure. AB - Coupling a two-dimensional (2D) semiconductor heterostructure to a superconductor opens new research and technology opportunities, including fundamental problems in mesoscopic superconductivity, scalable superconducting electronics, and new topological states of matter. One route towards topological matter is by coupling a 2D electron gas with strong spin-orbit interaction to an s-wave superconductor. Previous efforts along these lines have been adversely affected by interface disorder and unstable gating. Here we show measurements on a gateable InGaAs/InAs 2DEG with patterned epitaxial Al, yielding devices with atomically pristine interfaces between semiconductor and superconductor. Using surface gates to form a quantum point contact (QPC), we find a hard superconducting gap in the tunnelling regime. When the QPC is in the open regime, we observe a first conductance plateau at 4e2/h, consistent with theory. The hard-gap semiconductor superconductor system demonstrated here is amenable to top-down processing and provides a new avenue towards low-dissipation electronics and topological quantum systems. PMID- 27682269 TI - The Golgi associated ERI3 is a Flavivirus host factor. AB - Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3'-5' RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3' UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication. PMID- 27682267 TI - Noncontiguous double-level unstable spinal injuries. AB - PURPOSE: Noncontiguous double-level unstable spinal injuries (NDUSI) are uncommon and have not been well described. In this study, we aimed to better understand the patterns of NDUSI, in order to recommend proper diagnostic and treatment methods, as well as to raise awareness among traumatologists about the possibility of these uncommon injuries. METHODS: A total of 710 consecutive patients with spine fractures were treated for >9 years since 2007 at a single regional trauma center. Of them, 18 patients with NDUSI were reviewed retrospectively. RESULTS: The incidence of NDUSI was 2.5 % of all spine fractures. In 17 of 18 patients (94.7 %), NDUSI was caused by a high-energy trauma. Nine patients (50.0 %) exhibited complete neurological deficit. Spinal cord injury occurred in the cranial injured region in all American Spinal Injury Association grade A cases. In one case, a second fracture was overlooked at the initial examination. CONCLUSION: NDUSI are common in cases of high-energy trauma and should be taken into consideration at the initial examination. A second fracture may be easily overlooked because of the high frequency of concomitant severe spinal cord injury in the cranial injured region and/or loss of consciousness due to associated injuries. To avoid overlooking injuries, full spine computed tomography is useful at the initial examination. Operative reduction and internal fixation with instrumentation through a posterior approach is recommendable for cases of NDUSI. In elderly patients, a very rapid stabilizing surgery should be planned before aspiration pneumonia occurs or the pulmonary condition worsens. PMID- 27682271 TI - Microcephaly risk with RUSC2. PMID- 27682272 TI - Cross-sectional and Prospective Examination of Weight Misperception and Depressive Symptoms Among Youth with Overweight and Obesity. AB - This study aims to determine the association between weight misperception (considering oneself average or underweight) and depressive symptoms among youth with overweight/obesity. Linear regression models (adjusted for age, BMI, parental education, percent poverty) were used to examine cross-sectional (wave II, 1996, n = 3898, M age = 15.9, SD = 0.13) and longitudinal (from wave II to IV, 1996-2008/2009, n = 2738, M age = 28.5, SD = 0.06) associations between weight misperception and depressive symptoms (Center for Epidemiologic Studies Depression Scale) in a subsample of White, Black, Asian, Hispanic, and Multi racial male and female youth with overweight/obesity participating in the National Longitudinal Study of Adolescent Health. Average BMI was 29.0 (0.16) at wave II and 35.7 (0.23) at wave IV. Thirty-two percent misperceived their weight status as average weight (n = 1151, 30 %) or underweight (n = 99, 3 %). In fully adjusted cross-sectional models, White (beta = -1.92, 95 % CI = -2.79, -1.06) and Multi-racial (beta = -4.43, 95 % CI = -6.90, -1.95) youth who perceived themselves as average weight had significantly lower depressive symptoms compared to accurate weight-perceivers. In fully adjusted longitudinal models, White youth (beta = -0.41, 95 % CI = -0.81, -0.004) who perceived themselves as average weight had significantly lower depressive symptoms 12 years later. Findings suggest that weight misperception may be protective against depression among White adolescents and young adults with overweight/obesity. Clinical and population interventions should consider potential harmful effects of correcting weight misperceptions on the mental health of youth with overweight/obesity. PMID- 27682270 TI - Oviposition ecology and species composition of Aedes spp. and Aedes aegypti dynamics in variously urbanized settings in arbovirus foci in southeastern Cote d'Ivoire. AB - BACKGROUND: Aedes mosquito-transmitted outbreaks of dengue and yellow fever have been reported from rural and urban parts of Cote d'Ivoire. The present study aimed at assessing Aedes spp. oviposition ecology in variously urbanized settings within arbovirus foci in southeastern Cote d'Ivoire. METHODS: Aedes spp. eggs were sampled using a standard ovitrap method from January 2013 to April 2014 in different ecosystems of rural, suburban and urban areas. Emerged larvae were reared until the adult stage for species identification. RESULTS: Aedes spp. oviposition ecology significantly varied from rural-to-urban areas and according to the ecozones and the seasons. Species richness of Aedes spp. gradually decreased from rural (eight species) to suburban (three species) and urban (one species) areas. Conversely, emerged adult Aedes spp. mean numbers were higher in the urban (1.97 Aedes/ovitrap/week), followed by the suburban (1.44 Aedes/ovitrap/week) and rural (0.89 Aedes/ovitrap/week) areas. Aedes aegypti was the only species in the urban setting (100 %), and was also the predominant species in suburban (85.5 %) and rural (63.3 %) areas. The highest Ae. aegypti mean number was observed in the urban (1.97 Ae. aegypti/ovitrap/week), followed by the suburban (1.20 Ae. aegypti/ovitrap/week) and rural (0.57 Ae. aegypti/ovitrap/week) areas. Aedes africanus (9.4 %), Ae. dendrophilus (8.0 %), Ae. metallicus (1.3 %) in the rural, and Ae. vittatus (6.5 %) and Ae. metallicus (1.2 %) in the suburban areas each represented more than 1 % of the total Aedes fauna. In all areas, Aedes species richness and abundance were higher in the peridomestic zones and during the rainy season, with stronger variations in species richness in the rural and in abundance in the urban areas. Besides, the highest Culex quinquefasciatus abundance was found in the urban areas, while Eretmapodites chrysogaster was restricted to the rural areas. CONCLUSIONS: Urbanization correlates with a substantially higher abundance in Aedes mosquitoes and a regression of the Aedes wild species towards a unique presence of Ae. aegypti in urban areas. Aedes wild species serve as bridge vectors of arboviruses in rural areas, while Ae. aegypti amplifies arbovirus transmission in urban areas. Our results have important ramifications for dengue and yellow fever vector control and surveillance strategies in arbovirus foci in southeastern Cote d'Ivoire. PMID- 27682274 TI - Variety in diagnosis and treatment of periprosthetic joint infections in Belgium and the Netherlands. AB - Recently, guidelines regarding diagnosis and treatment of periprosthetic joint infection (PJI) have been published, but it is unknown how well these are followed in the Netherlands and Belgium. Therefore, a survey study was performed in the Netherlands and Belgium. 81 orthopedic departments responded (54% in the Netherlands, 52% in Belgium). The majority used protocols for antibiotic and surgical treatment. To discriminate between early and late infection, differences in periods used were seen between respondents, and between countries. Empirical antibiotic treatment varied greatly. Debridement, antibiotics, irrigation and retention of the prosthesis (DAIR) is the -almost unanimous treatment of choice for early PJI. Guidelines are available, but seem not (yet) to be -followed accurately, and do not have answers to all possible treatment options. Perhaps, national guidelines might produce more standardized care, and -consequentially, easier comparison for research, more transparency for patients, and less health care costs. PMID- 27682273 TI - Exploring Couples' Processes of Change in the Context of SASA!, a Violence Against Women and HIV Prevention Intervention in Uganda. AB - There is now a growing body of research indicating that prevention interventions can reduce intimate partner violence (IPV); much less is known, however, about how couples exposed to these interventions experience the change process, particularly in low-income countries. Understanding the dynamic process that brings about the cessation of IPV is essential for understanding how interventions work (or don't) to reduce IPV. This study aimed to provide a better understanding of how couples' involvement with SASA!-a violence against women and HIV-related community mobilisation intervention developed by Raising Voices in Uganda-influenced processes of change in relationships. Qualitative data were collected from each partner in separate in-depth interviews following the intervention. Dyadic analysis was conducted using framework analysis methods. Study findings suggest that engagement with SASA! contributed to varied experiences and degrees of change at the individual and relationship levels. Reflection around healthy relationships and communication skills learned through SASA! activities or community activists led to more positive interaction among many couples, which reduced conflict and IPV. This nurtured a growing trust and respect between many partners, facilitating change in longstanding conflicts and generating greater intimacy and love as well as increased partnership among couples to manage economic challenges. This study draws attention to the value of researching and working with both women, men and couples to prevent IPV and suggests IPV prevention interventions may benefit from the inclusion of relationship skills building and support within the context of community mobilisation interventions. PMID- 27682275 TI - Acromioclavicular joint cyst in ASA 3-4 patients.Whether and how quickly it recurs after aspiration and steroid injection. AB - We observed the clinical course, in the short-medium term, of patients with voluminous type II acromio-clavicular (AC) joint cyst who underwent aspiration and steroid injection regarded as the only possible treatment to avoid possible skin complications. Four patients (7.4% of cases described in literature) (3F-1M ; mean age 83 years, range : 78-87 years) with a voluminous ( > 7 cm) oval, no mobile, no fluctuant cyst overlying the AC joint, were retrospectively observed. The patients, judged by the anesthesiologist as ASA 3-4 patients, were merely submitted to cyst aspiration and steroid injection. The content of the cyst was microscopically analysed. All patients were clinically evaluated on the day of aspiration and after 14-30 days and after 1 year. Shoulder function and pain intensity were analysed with Constant score and VAS. We were able to aspirate 80 150 ml of amorphous joint fluid. At the first follow-up, all patients had a recurrence of the cyst, a lower grade of tension of the skin overlying the cyst and also a very little decreasing of pain intensity. After a month from aspiration, the cysts of the 4 patients had the same size as that present before aspiration. The range of motion, the average value of VAS and Constant were similar to those recorded before aspiration. In no case signs of infection or draining sinus occurred. Aspiration is a useless practice. However it is still a motive for discussion if the reduced suffering of the skin overlying the cyst after the aspiration has avoided, or simply postponed, an imminent complication. PMID- 27682276 TI - Empty can and drop arm tests for cuff rupture : Improved specificity after subacromial injection. AB - : Shoulder disorders are common in the general population : they occur in about 25 of every 1000 patients per year. A rather large majority are caused by cuff disorders. Differentiating between impingement and cuff rupture is essential to adequate treatment. Clinical tests have been developed, but their accuracy is limited. This study was performed to improve clinical accuracy by combining single tests and adding a subacromial injection. We postulated that the empty can and drop arm tests would result in higher sensitivity and specificity after subacromial injection. METHOD: We prospectively assessed 49 patients with the empty can and drop arm tests and used ultrasound to compare the individual and combined results. RESULT: The ultrasound found six cuff ruptures. Specificity improved and sensitivity decreased after subacromial injection. CONCLUSION: Only specificity improved after subacromial injection. Combining the test results led to an increase in both sensitivity and specificity without injection. PMID- 27682277 TI - Radiological and clinical outcome of arthroscopic labral repair with all-suture anchors. AB - Purpose : The aim of this study was to assess radiological and clinical outcome after arthroscopic all--suture anchor labral repair. Method: 20 patients treated for anterior and superior labral instability (mean age 29, range 14-51 years) were assessed at a minimum follow-up time of 1 year (mean 19 months ; range, 12 28 months). Postoperative MRI scans were assessed by 3 independent radiologists. The radiological appearance of bone at the anchor-site was judged by the presence of cyst formation, tunnel widening (> 2 mm) or bone edema. Clinical outcome analysis included standard follow-up and the Disabilities of the Arm, Shoulder and Hand score (DASH), Constant Shoulder score and the Western Ontario Shoulder Instability Index (WOSI). result: All patients were available for follow-up. In total, 58 all-suture anchors were implanted. None of the patients displayed large cyst formation. Small cysts were found in two patients (2 anchors). Tunnel widening was apparent in 3 patients (3 anchors) with an average widening of 3.3 mm (range 3-4 mm). Bone edema at the anchor-site was seen in 6 patients (8 anchors). The remaining 9 patients (45 anchors) did not display reactive bone changes. Clinical outcomes showed a WOSI of 70.6, a DASH of 18.9 and a Constant score of 89.3, and no recurrence of instability. Conclusions : Satisfying radiological and clinical outcome was observed after arthroscopic instability surgery using all-suture anchors. Imaging revealed good labral healing without important bony reactions or the formation of large cysts at early follow-up. Level of evidence : IV Case series. PMID- 27682278 TI - Histological and biochemical evidence related to the collagen quality in torn rotator cuff tendons. AB - This study investigates the histological background of torn rotator cuff tendons, evaluates the stability of newly synthesized collagen by measuring the hydro xyproline content and attempts to correlate these findings with the clinical outcome after reconstruction of the rotator cuff. Sixty-one patients underwent reconstruction for a -rotator cuff tear. They were evaluated preoperatively with the Constant-Murley score, MRI and ultrasound. Biopsy samples were taken from chronic rotator cuff tears and histological analysis was performed. Hydroxyprolin presence was evaluated in various -tissues. Mean follow-up was 46 months. Histological analysis revealed collagen fragmentation and thinning (90.2% of patients), myxoid degeneration (88%), hyaline degeneration (50.8%), chondroid metaplasia (44.3%), calcification (24.7%), fatty infiltration (20.4%) and vascular proliferation (62.3%). Hydroxyproline was under-represented in newly synthesized collagen in 57% of patients. In the majority of the patients with a low hydroxyproline/collagen ratio the histological findings were abnormal. None of the findings was related to the clinical outcome with a statistical significance. Histological and biochemical findings reflected the poor quality of the tendon. The good clinical outcome did not depend on the histological or biochemical findings but rather on the meticulous surgical reconstruction and physical therapy. PMID- 27682279 TI - The necessity of strength evaluation in assessment of clinical outcome after shoulder surgery : follow-up data from patients with complex proximal humerus fractures treated by locking plate fixation. AB - In order to minimize the bias of Constant score we modified the allocation of strength subscore. One hundred and two patients with 3- and 4-part proximal humerus fractures were treated using locking plate fixation and followed up for > 1 year. The clinical outcomes were assessed by DASH score abbreviated Constant score (AbbCS strength item excluded) modified Constant score (ModCS with 12-pound strength) and original Constant score (CS with 25-pound strength). The satisfaction rate was determined for each scoring instrument. Compared to CS the satisfaction rate was significantly higher in DASH score AbbCS and ModCS (all p < 0.001) but the latter 3 groups did not show significant difference. ROC analysis showed that a > 7-pound shoulder strength was present in patients with satisfied outcome assessed by DASH score. In conclusion strength evaluation is necessary for the assessment of shoulder function but the over-allocated strength should be modified in Constant score. PMID- 27682280 TI - Avulsions of Triceps Brachii : associated injuries and surgical treatment ; a case series. AB - This study reports the clinical presentations, intra -operative findings, type of the treatments, outcome of the treatment and specially associated injuries in patients with the avulsion of the distal end of the triceps brachii (TB) tendon. We studied 6 patients with rupture or avulsion of the distal end of the TB tendon. The medical records, imaging files, clinical outcomes at the final follow up visit were reviewed. The clinical outcomes were assessed by Mayo Elbow Score at the final follow-up visit. All patients were male, 4 of them having injury in the left hand as the non-dominant hand. Mean age of them was 34.5 years. All cases had small bony fleck in the posterior of elbow in lateral radiograph. Three patients had associated injuries -including intra-articular fractures and medial collateral ligament rupture. In one case V-Y plasty of the distal TB was done. In 4 patients the results of surgery were excellent, one was good and one was fair. Although TB tendon rupture is rare, it should be -considered in differential diagnosis of the upper -extremity trauma and its associated injuries should be addressed properly. PMID- 27682281 TI - The value of manipulation of displaced distal radius fractures in the emergency department. AB - The aim of this study was to report the success of maintaining reduced distal radius fractures with cast immobilisation and analyse risk factors for redisplacement. A retrospective analysis of distal radius fracture manipulated between April 2011 and 2013 was conducted. Age, gender, fracture classification, ulna fracture, dorsal comminution and volar alignment were recorded. Reduction and redisplacement were measured using Sarmiento's modification of Lidstrom's system. 110 patients were included ; mean age 62.8 years and 83.4% female. The AO classification was used to grade initial fractures A2 (44%), A3 (25%), C1 (20%) and C2 (10%). 86.4% of cases were improved following manipulation, although 48.4% redisplaced and 27.4% required surgical intervention. The radial length (60%) was harder to maintain than dorsal alignment (44%) in cases of redisplacement. Successful alignment of the volar cortices was associated with a statistically significant reduction in redisplacement (p = 0.024). Manipulation of distal radius fractures is initially beneficial but half of cases redisplace. PMID- 27682282 TI - Scaphoid nonunion with carpal ligament injury - radiological, arthroscopical assessment and clinical results. AB - The purpose of this study was to review the clinical results of carpal ligaments injuries with scaphoid nonunion. We hypothesized that scaphoid nonunion with carpal ligament injury is associated with clinical result. We retrospectively reviewed 60 cases of -Herbert screw fixation with bone graft for scaphoid nonunions. Scapholunate (SL) and lunotriquetral (LT) ligaments lesions were confirmed by arthroscopy. Approximately half of the nonunion scaphoid cases had carpal ligaments injuries. At final follow-up evaluation, wrist function as evaluated by the Mayo wrist score was excellent in 34 patients, good in 16 patients, fair in 8 patients, and poor in 2 patients. Cases with both SL/LT ligaments injuries tended to have decreased wrist flexion-extension motion. Our results suggest that there is an indication for arthroscopy in scaphoid nonunion if surgical fixation is offered to avoid detrimental effects of an undiagnosed ligament tear. PMID- 27682283 TI - Non-Metastatic Pelvic Ewing's Sarcoma : oncologic outcomes and evaluation of prognostic factors. AB - We are reporting our experience on patients with -pelvic Ewing's Sarcoma treated in our unit. We retrospectively reviewed a series of patients with non-metastatic pelvic Ewing's sarcoma treated between 1977 and 2009. Patients were classified into three groups according to the local treatment received : Group 1. radiotherapy-chemo ; Group 2. surgery-chemo and Group 3. radiotherapy-surgery chemo. Recurrence free and overall survival rates were calculated using the Kaplan-Meier method. Influence of various factors (age at diagnosis, gender, tumour site and size, chemotherapy response, surgical margins and type of treatment) on survival was assessed with a logistic regression model. A total of 85 patients were treated with a mean follow-up of 65.8 months and mean -tumour volume of 435ml. The 5-year survival for all patients was 40.7% decreased to 36.2% at 10 years. A significant prognostic factor identified was chemotherapy response only. There was a trend for improved survival and local control rates for patients who had chemotherapy and surgery and the results were apparent for all tumours irrespective of size but not statistically significant. Currently, the optimal management of pelvic Ewing's sarcoma is contro-versial but our study shows a trend for improved -survival for patients treated with chemotherapy and surgery. PMID- 27682284 TI - The reliability and validity of the Unified Classification System of periprosthetic femoral fractures after hip arthroplasty. AB - The Unified Classification System has expanded and updated the Vancouver Classification System and applied treatment principles to all periprosthetic fractures. This study assessed the reliability and validity of the Unified Classification System for femur fractures after hip arthroplasty. Thirty-eight radiographs were finally evaluated by 6 observers, 3 consultants and 3 trainees. Each observer read the radiographs on 2 separate occasions, independently, at least 2 weeks apart. Interobserver and intraobserver agreement and validity were analyzed, using weighted kappa statistics. The mean kappa value for interobserver agreement was found to be 0.849 (0.838-0.871) for consultants (almost perfect agreement) and 0.761 (0.707-0.836) for the trainees (substantial agreement). Intraobserver kappa values ranged from 0.740 to 0.903, showing substantial to almost perfect agreement. Validity analysis of 23 type B cases revealed 79.710% agreement within B1, B2, and B3 subgroups with a mean kappa value of 0.694 (0.670 0.741) (substantial agreement). PMID- 27682285 TI - Augmentative compression plating versus exchanging reamed nailing for nonunion of femoral shaft fracture after intramedullary nailing : A retrospective cohort study. AB - Aim of the present study was to compare the outcomes between exchanging reamed nailing (ERN) and augmentative compression plating (ACP) in treatment of femoral shaft nonunion after intra-medullary nailing (IMN) retrospectively. A retrospective, multicentre study was performed with 188 patients (190 cases)with femoral shaft nonunion after IMN, who received therapy with either ERN (n = 92) for 44/92 (47.8%) cases of nonisthmal nonunions and 48/92 (52.2%) cases of isthmal nonunions or ACP (n = 98) for 48/98 (49%) cases of nonisthmal nonunions and 50/98 (51%) cases of isthmal nonunions. Operation time, intraoperative blood loss, time to union, union rate, postoperative draining volume and complication rate were compared between ERN and ACP group. After a mean follow-up of 4.6 years (range 1-8.1 years), the bone union occurred in 98/98 (100%) cases in -total ACP group versus 80/92 (87%) cases in total ERN group [odds ratio (OR) = 3.34, 95% confidence interval (CI) 0.8-1.6]. Twelve cases with re-nonunion in the total ERN group included 10/12 (83.3%) cases of nonisthmal nonunions and 2/12 (16.7%) cases of isthmal nonunion with cortical bone defect > 3 cm. The average time to union, the intraoperative blood loss and the complication rate in total ERN group were also both significantly more than that in total ACP group (p = 0.031, p = 0.042, p = 0.028). No -significant difference was found in the average operation time between the two total groups (p = 0.213). However, for nonisthmal nonunions, the mean operation time for ERN group was 126.8 +/- 19.6 min in -comparison to ACP group (88.6 +/- 15.2 min), significant difference was found between ERN group and ACP group (p = 0.021). ACP could obtain the higher bone union rate and shorter time to union than ERN in the treatment of femoral shaft nonunion after failed IMN. Especially for nonisthmal femoral shaft nonunions or isthmal. PMID- 27682286 TI - A posteromedial approach for open reduction and internal fixation of posteromedial tibial plateau fracture. AB - The aim of this study was to evaluate the clinical outcomes of patients with posteromedial tibial plateau fractures treated by open reduction and internal fixation (ORIF) through a posteromedial approach. Thirty-six patients with posteromedial tibial plateau fracture underwent ORIF through a posteromedial approach and were retrospectively analyzed. Pre-operative X-ray pictures and CT images were -obtained. And there were 11 cases of posteromedial tibial plateau fracture and 25 cases of posteromedial and posterolateral tibial plateau fracture. All the -patients were treated surgically with posteromedial approach. The clinical outcomes were assessed -according to the Rasmussen knee function grading system. The patients were followed-up for an average of 17.5 months (range, 12-32 months). All the fractures attained satisfactory reduction. No major complications were observed. According to the Rasmussen knee function grading system, the results were graded as excellent in 21 cases, good in 13 cases, fair in 2 cases. The rate of excellent and good results was 94.4%. The posteromedial approach in our opinion is the best option to treat the posteromedial tibial plateau fractures because it can provide direct visualization of the fracture site and avoid dissection of neurovascular bundle in the popliteal fossa area with minimal soft tissue injury. PMID- 27682287 TI - Postoperative pain relief and functional outcome following total knee arthroplasty - a prospective comparative audit of three analgesic regimes. AB - Pain control plays a key role in joint-replacement -surgery. As a surgeon the challenge is to reduce pain to an acceptable level in the post-operative period. The aim of the study was to assess the efficacy of bolus -local anaesthesia, infusion in to the surgical site and nerve blocks with femoral nerve catheter and its functional outcome. A prospective audit of 114 patients undergoing total knee arthroplasty were carried out.The patients were divided in to three groups : Group 1 (n = 27) received a bolus injection of 20 ml 0.25% levobupivacaine + 10 ml 0.25%bupivacaine + adrenaline + 30 ml saline. Group 2 (n = 39) received a bolus injection as on group 1 with 240 ml 0.25% bupivacaine infusion and 5 ml/hour using a Pain Buster pump. Group 3 (n = 48) received 30 ml 0.125% levobupivacaine to femoral (3-in-1) block with 30 ml 0.25% levobupivacaine to sciatic nerve and introduction of a femoral nerve catheter. All patients were prescribed paracetamol 1 g QDS, Oxycontin 20 mg BD and Ibuprofen post operatively. Pain was assessed with a Visual Analog Scale (VAS). The incidence of PONV was measured by PONY intensity score. The mean post-op VAS score for Group 3 was 4. The demand of oxynorm and NSAID were minimal in Group 3. The mean in patient stay for Group 3 was 3.1 days. The PONV intensity score was > 50 for 9 (36%) in Group 1, 15 (40%) in Group 2 and 9 (20%) in Group 3. There was loss of 20-30 degrees of flexion movements in Group 3 in the first 4 to 6 days post-op. Our study demonstrated that Regime 3 with the use of nerve blocks and femoral nerve catheter has given the maximum pain relief and good functional outcome following total knee replacement. PMID- 27682288 TI - Pedobarographic measurements after repair of Achilles tendon by minimal invasive surgery. AB - The aim of the current study was to assess the changes of plantar foot pressures with pedobarography in -patients with Achilles tendon repair by minimally invasive surgical technique. This retrospective study consisted of 15 consecutive patients who were treated for acute Achilles' tendon repair with minimally invasive technique in our clinic in a two year period between 2010 and 2012. All patients were male. The mean age was 28.7 years (24-42) and the mean follow-up time was 2.3 years (1.5- 3). All patients had sports related Achilles' tendon rupture and all had undergone surgery in 24-48 hours. After surgery, extremity was immobilized with short leg cast for 6 weeks. Peak and mean heel and forefoot pressures in injured extremity were measured by -pedobarograph and compared with noninvolved foot. There wasn't any complication associated with -surgery such as wound problems, re rupture or -neurologic injury. Only three patients had some numbness at the incision site. When we compare the mean foot pressures between the operated foot and the normal foot, there was no statistical difference about peak and mean heel and forefoot plantar pressure between involved site and non involved site. As a result, Achilles tendon repair with minimal invasive technique and early rehabilitation may prevent changes of plantar foot pressure distribution. PMID- 27682289 TI - Heel reconstruction with parallel fibular osteoseptocutaneous flap. AB - Reconstruction of heel defects can be challenging and requires careful consideration in restoring both the functional and aesthetic deficit. This study assessed the use of parallel fibular osteoseptocutaneous flap to repair composite heel defects. Follow-up of the 4 patients included in this study ranged from 24 months to 3 years after their operation. The flap survival rate was 100% in all patients, with good coverage of the heel defects. Postoperative complication was one -superficial wound infection. Union of the graft with the host bone was achieved in all patients at an average of 6 months (range : 5-10 m/onths). The parallel fibular osteoseptocutaneous flap is thus a reliable means of reconstruction of composite bone and soft-tissue -defect in the heel region. PMID- 27682290 TI - Evaluation of the metaphyseal ulnar shortening technique according to Sennwald. AB - : The outcome of a metaphyseal ulnar shortening osteotomy, reported by Sennwald as an alternative option for ulnar abutment syndrome, was evaluated with -regard to the functional results, pain relief and incidence of complications. METHOD: We conducted a review of 12 patients ; measured parameters were DASH score, PRWE, VAS for pain, grip force and wrist motion. RESULTS: Only disability improved significantly with a DASH score of 42 (p = 0.03). The function and pain assessment scores did not improve in 3 patients. We found no correlation between change in functional scores and other measured variables. Six patients were reoperated for prominent screw heads or new-onset distal radioulnar joint osteoarthritis. CONCLUSION: All osteomies healed fast and uneventfully and disability improved in most patients but 25% did not improve and 50% were re operated. Further investigation is needed to evaluate the value of the metaphyseal osteotomy as an alternative treatment for ulnar abutment syndrome. PMID- 27682291 TI - Gait analysis in tumor patients after distal femoral resection and implantation of a megaprosthesis. AB - We analysed nine patients who had had a megaprosthesis implanted into the distal femur and knee joint for treatment of sarcomas. Data obtained from the leg operated on were compared with those from the contralateral side and healthy volunteers. Gait data, kinematics, ground reaction forces and the EMG from five muscles around the knee joint were analysed by means of a video-based analysis system recording data from reflection markers ; a Kistler-plate recorded the GRF and a ten channel surface EMG the muscle activity. Muscle around the knee showed a cocontraction between the extensor and flexor muscles in the thigh and the calf in the operated leg as well as contralaterally. Gait characteristics exhibited a reduced speed, -cadence, and a shorter step. This correlated with a reduced flexion in the hip and knee joint. The GRF exhibited significant changes in the data representing the reduced gait dynamic. PMID- 27682292 TI - Bicondylar tibial plateau fractures involving the posteromedial fragment : morphology based fixation. AB - The aim of this study is to describe the morphology of the posteromedial fragment in the setting of bicondylar tibial plateau fractures and to use it as a base for selection of the method of fixation. Twenty two -patients with bicondylar tibial plateau fractures -involving the posteromedial fragment were included in this study. Plain X- ray and computed tomogram (CT) were performed in all patients. Thirteen patients were treated by dual plating while nine were treated by single lateral plate. The mean posteromedial fragment height was 39 mm. The cephalad surface area percentage of the posteromedial fragment relative to the entire tibial plateau ranged from 10% to 43%. with an average of 28%. The average knee motion at the final follow up was 110 degrees . Two cases were complicated by implant failure. Morphological study of the posteromedial fragment could help in selection of the proper method of fixation. PMID- 27682293 TI - Analysis of soft-tissue complications of volar plate fixation for managing distal radius fractures and clinical effect while preserving pronator quadratus. AB - The aim of the study was to analysis soft-tissue complications of volar plate fixation and it's prevention strategies along with exploring clinical effects of preserving pronator quadratus (PQ) muscle. From February 2011 to February 2013, sixty-five patients with distal radius fracture underwent open reduction and internal fixation with the volar locking palmar plates. The group with preserving PQ involved 30 patients and group with PQ repair involved 35 patients. Surgeons must took great care of not -letting drill pierce dorsal cortical bone rapidly and dorsal carpal tangential fluoroscopy was also taken in addition to lateral fluoroscopy to get accurate screw length. Volar plate must be placed not go beyond the watershed region of distal radius. The wrist pain, forearm range of motion, grip strength, wrist functional recovery score, X-ray and CT imaging were followed-up after surgery. Two groups were compared for Clinical efficacy. The minimum follow-up for the whole cohort was one year. The relevant post operative data were collected after 2 weeks, 6 weeks, 3 and 12 month respectively. Fractures healing after postoperative 3 months are significant in X -ray and CT imaging. Fixation position and stability were good, but each group had one case with a screw piercing the dorsal cortical. The -differences between the two groups were significant regarding the wrist pain, forearm range of motion, grip and strength at 2 and 6 weeks after operation, but not significant at 3 and 12 month after operation. The differences between the two groups were also significant regarding wrist functional scores at 6 weeks, but not significant at 3 and 12 month after operation. Drilling the dorsal cortical bone gently and accurate screws length can avoid extensor tendon injury. -Dorsal carpal tangential fluoroscopy is a useful supplement for accurate screws length besides lateral fluoroscopy. Volar plate's position not go beyond the watershed region of distal radius is the key factor in reducing the flexor tendon injury and preservation of the PQ muscle can also prevent the flexor tendon -injury, yield better early wrist function and shorten rehabilitation time. PMID- 27682294 TI - Morphological characteristics of olecranon fractures in adults : a Computed Tomography-based study. AB - The aim of this study was to identify the fragment's shape by evaluating olecranon fractures. We examined the CT images of 48 olecranon fractures (28 women and 20 men). Mean age was 59.9 years. On the olecranon's posterior surface, we measured the distance between the apex of the olecranon fragment and the radial edge of the flat spot on the short axis and the width of the flat spot on the same short axis. The tip radial ratio (i.e., the tip radial edge to the flat spot width) was derived from these parameters. The mean tip radial edge was 1.96 mm, and the flat spot width was 12.64 mm ; therefore, the tip radial ratio was 0.15 mm. Radial inclination on the articular surface was 30.55 degrees . Our findings confirmed our hypothesis that the fracture lines run from the proximal ulnar side to the distal radial side on the olecranon's posterior and articular surfaces. PMID- 27682295 TI - Does the implant make the difference ? - Prospective comparison of two different proximal femur nails. AB - The aim of this study was to compare two proximal femur nails with regard to the complication rate and midterm clinical outcome : the InterTAN nail (ITN) versus the third generation gamma nail (GN). 78 patients older than 60 years with an unstable intertrochanteric femoral fracture (AO/OTA 31 A2/A3) were randomised over a 20 month period into either ITN (n = 39) or GN (n = 39). The outcomes of interest were the perioperative implant-related complications and the functional status (Harris Hip Score) at 6 months postoperatively. In 14 of the ITN and in two of the GN procedures the surgeons rated the implant as cumbersome (p = 0.002). Functional outcome and complication rate did not differ between both groups. The mechanical failure correlated with the positioning of the lag screw independent on the used implant. The surgeon's technique (closed reduction, positioning of lag screw) and not implant configuration, is of crucial importance in achieving successful outcome. PMID- 27682296 TI - Four-corner arthrodesis using two headless compression screws. AB - We present the outcome of four-corner wrist arthrodesis using two headless compression screws for fixation. The study group consisted of 27 patients who underwent arthrodesis from 1998 through 2007. Data on demographic parameters, diagnosis, range of motion, pain and complications were collected from the medical files. A total of 77 series of anteroposterior, oblique, and lateral x rays were reviewed by three independent interpreters ; consensus of at least two was required for the bones to be considered fused. Fusion was achieved in 24/27 wrists. Overall, inter-observer agreement in identifying radiographic bony fusion was fair (kappa = 0.41). At the critical timing, 86 (SD 68) days postoperatively, when the decision regarding -fusion was made, inter-observer agreement was poor (kappa = 0.07). Our rates of fusion are consistent with -reports in the literature. Radiographs performed at 3 months after four-corner arthrodesis are not -reliable for the diagnosis of fusion. PMID- 27682297 TI - Arthroscopic treatment of the young degenerative shoulder joint ; is there a role for interpositioning arthroplasty ? AB - We evaluate our experience with arthroscopic interpositioning arthroplasty as a treatment of the young degenerative shoulder joint. Between 2007 and 2009 ten patients were treated with either a dermal allograft or a meniscal allograft. In seven patients the graft failed and within 13 months these were revised to a total shoulder arthroplasty. Three patients are still satisfied after 7 to 8 years follow-up. Biologic resurfacing of the glenoid may have a role in the management of glenohumeral arthritis in the young and active patient, but the optimal graft and pathology still need to be defined. PMID- 27682298 TI - Dynamic hip screw fixation of intertrochanteric fractures without using traction table. AB - To evaluate a new technique of Dynamic hip screw (DHS) fixation without using traction table. From july 2006 to july 2012, 328 patients undergoing DHS fixation using manual traction technique were evaluated in terms of Tip apex distance (TAD), -quality of fracture reduction, operation time, preoperative preparation time. In 97% cases good to moderate reduction could be achieved. The mean TAD was 19.2 millimeters, mean operation time 37 minutes and screw cutout rate was only 0.91%. This technique is easy, reproducible, cheap do not sacrifice reduction alignment, screw position and is extremely beneficial in polytrauma patients where multiple surgeries are to be done. PMID- 27682299 TI - Median nerve biodegradable wrapping : Clinical outcome of 10 patients. AB - Nerve wrap protectors are bioabsorbable synthetic materials made of collagen or extracellular matrix that provide a non-constricting encasement for injured peripheral nerves. They are designed to be used as an interface between the nerve and the surrounding tissue. After hydrated, they transform into a soft, pliable, nonfriable, easy to handle porous conduit. The wall of the nerve wrap has a longitudinal slit that allows to be placed around the injured nerve. Tauhis article presents the surgical technique for median nerve neurolysis and nerve coverage using a collagen or an extracellular matrix nerve wrap protector in 10 patients with recurrent or persistent carpal -tunnel syndrome. All patients had a mean of three previous open carpal tunnel operations, which were not successful. The mean follow-up was 3 years. -Under axillary nerve block anaesthesia with the use of -pneumatic tourniquet, a standard open carpal tunnel approach was done incorporating the previous incision. Scar tissue was excised in a healthy bed and the median nerve was thoroughly released with external neurolysis. An appropriate length of nerve wrap protector was cut longitudinally according to the length of nerve release. The nerve wrap was loosely sutured with separate polypropylene sutures No. 7-0. A volar splint was applied for a mean of 2 weeks followed by progressive passive and active range of motion rehabilitation exercises of the wrist and fingers. At the last follow-up, all patients showed improvement of clinical symptoms, static two-point discrimination test and median nerve conduction studies, and absence of Tinel sign. Differences in outcome and complications with respect to the nerve wrap materials used were not observed. PMID- 27682300 TI - Supplementary tibial fixation in anterior cruciate ligament reconstruction - Direct cortical fixation using spiked washer screw vs. post-tie using washer screw. AB - We compare clinical outcomes of two different supplementary tibial fixation in anterior cruciate ligament (ACL) reconstruction using free tendon Achilles allograft. Eighty subjects underwent ACL reconstruction using Endobutton CL for femoral fixation and Bio-interference screw for tibial fixation. Supplementary tibial fixation was performed as direct -cortical fixation using spiked washer screw (group I) or as post-tie using washer screw (group II). -Lachman test, pivot shift test, IKDC classification, Lysholm score, and side-to-side difference (SSD) were evaluated. Thirty six in group I and thirty five in group II could follow up for at least 2 years. At the last follow-up, 7 in group I and 1 in group II showed 2+ or 3+ in Lachman test (p = 0.027). Mean SSD was 2.4mm in group I and 1.4mm in group II (p = 0.048). Post-tie using washer screw was more effective than direct cortical fixation using spiked washer screw to restore stability. Level of evidence : Therapeutic Level I ; Randomized controlled clinical trial. PMID- 27682302 TI - Prospective mid-term results of a consecutive series of a short stem. AB - A large number of short stem prostheses for hip -arthroplasty have been introduced in the past years. Although there is a large increase of publications about short stems, there is still little data available about survival and revision rates. We report prospectively on the outcome of 84 consecutive NANOS(r) short stem prostheses in 81 patients. We have included 37 female patients and 44 male patients with an average age of 61.6 +/- 9.2 years. The main diagnoses were osteoarthritis in 67 patients, dysplastic osteoarthritis in 8 patients and avascular necrosis of the femoral head in 6 patients. Along with demographic data and co-morbidities, the Harris Hip Score was recorded preoperatively and at follow-up. The Harris Hip Score increased from 36.6 +/- 14.5 preoperatively to 94.5 +/- 8.8 at the final follow-up. During the main follow-up time (27.7 months +/- 5.7) none of the 84 stems were revised, intraoperatively three fissure fractures occurred. PMID- 27682301 TI - Outcomes of combined tibial tuberosity transfer and medial patellofemoral ligament reconstruction for recurrent patellar instability. AB - Patellofemoral instability is multifactorial and is associated with pathomechanics secondary to anatomical variance. Surgical management of this problem must be tailored to each patient and a thorough clinical and radiological assessment of the anatomical alignment should be carried out pre-operatively. The aim of this study is to assess the role of medial patellofemoral ligament reconstruction combined with tibial tuberosity transfer in patients with increased tibial tuberosity to trochlear groove (TT-TG) distance. Twenty-four patients (27 knees) over 2-years were operated on by a single surgeon, with standardised post-operative rehabilitation and follow up. Mean follow up was 31 months. Two patients had problems with recurrent instability, 1 had a -traumatic re-dislocation at 2 years and a total of 4 required further operation for complications. Mean post--operative Kujala scores were 87.4 (SD 9.8). Combined medial patellofemoral ligament reconstruction and tibial tuberosity transfer is an appropriate treatment for patients with increased TT-TG distance. PMID- 27682303 TI - Atypical femur fractures - Patient characteristics and results of intramedullary nailing for a series of 21 patients. AB - Atypical femoral fractures have been associated with long term use of bisphosphonates. Our study plan was to report the outcome of treatment for a series of -patients with an atypical femoral fracture and to compare the characteristics of those patients with a proximal femoral fracture. 21 atypical fractures were identified over a seven year period and these were compared with those of 2.547 hip fracture patients treated over the same time period at a single centre. The mean age of patients with an atypical fracture was on average nine years less than that for the hip fracture patients (72 as against 81 years, p = 0.002). Four (19.0%) of the patients with atypical fracture had no injury associated with the fracture and nine (42.9%) patients had pain prior to presentation at hospital for a mean of 31 days. Patients with atypical fractures were more likely to be smokers (9/21(42.9%) versus 319/2547 (12.5%), p = 0.0001) and more likely to be on long term oral steroid therapy (8/21 (38.1%) versus 131/2547 (5.1%), p < 0.0001) in comparison to other hip fracture patients. All the atypical fractures were treated by intramedullary nailing and healed uneventfully apart from one fracture that developed non-union requiring revision nailing. Residual pain at one year from injury was more prevalent for patients with atypical fractures. PMID- 27682304 TI - Long term results after bipolar radial head arthroplasty. AB - Radial head fractures are common injuries, occurring mostly in active young people 85%. Treatment of the more complex radial head fractures (Mason type III and IV), appear to be challenging and remain a subject of controversy. Replacement of the radial head with a metal prosthesis imitates the stabilizing role of the radial head and has been considered as the treatment of choice. However, long-term results are scarce. We report our mid to long-term (mean 9.4 year) clinical and radiographic results after insertion of a Judet Bipolar Radial Head prosthesis. 34 patients were treated with the Judet Bipolar Head prosthesis between 2000 and 2008. In this study, 21 patients were re-examined after a mean period of 113 months (range, 174-84), ie, 9.4 years (range, 14.5-7). Follow-up examinations included both the Mayo Elbow Performance Index (MEPI) and Dis- abilities of the arm, shoulder and hand (DASH) score. Range of motion was measured with a hand goniometer. X-rays were evaluated for peri-articular ossifications, radiolucent lines and signs of proximal erosion, capitellar erosion. Mean Mayo Elbow Performance Index was 88.6 (Range 100-50). According to the MEPI score we had 14 excellent, 1 good, 5 fair results and one poor result. One patient reported severe pain, 3 patients reported moderate pain, one patient reported mild pain and 16 patients reported no pain at all. Difference between pronation-suppination range was noted between primary or secondary indication of the radial head, no other significant differences were found. Mean DASH score was 23.1 degrees (Range 0-63) without difference between primary and secondary indication. Mean flexion was 121.8 degrees (Range : 110-140), mean extension deficit was 24.8 degrees (Range 15-40), mean pronation was 62.4 degrees (Range : 50-80) and suppination 58.8 degrees (Range : 45-80). Ten patients showed signs of ulnohumeral joint degenerative arthritis. One patient developed symptomatic ulna plus. One patient showed radiolucent lines surrounding the prosthesis with proximal bone erosion. There were no reports of dislocations of the prosthesis. One case of radiological signs of overlenghtening was noted. Mainly good clinical results are achieved with the -Judet bipolar radial head implant. Functional results after long term follow-up are, however less optimistic then the excellent results achieved after short- to mid-term follow-up. No clear link between radiological signs and functional results can be found. PMID- 27682306 TI - How often absence of palmaris longus and functional deficiencyof flexor digitorum superficialis occurs ? AB - This study was designed to find a possible correlation between the presence of the palmaris longus and function of the fifth flexor digitorum superficialis. We examined 300 participants to assess the absence of palmaris longus and flexor digitorum superficialis function by several clinical tests. Overall absence of palmaris longus, was seen in 157 participants (52.3%). Overall deficiency of flexor digitorum superficialis was noted in 100 participants (33.3%). In 15 participants (5%) we noted bilateral absence of palmaris longus and flexor digitorum superficialis deficiency. Five participants (1.7%) had unilateral absence of palmaris longus and flexor digitorum superficialis deficiency on the same, left or right hand. Bilaterally presence of these muscles we noted in 95 participants (31.7%). We believe that there is no connection between absent palmaris longus and absent function of flexor digitorum superficialis. We found a much higher prevalence of muscles absence individually and jointly than in other studies. PMID- 27682307 TI - Unilateral lumbar interbody fusion (ULIF). AB - Results and clinical outcome of a prospective multicenter clinical study involving 100 patients under-going a lumbar interbody fusion procedure using an unilateral approach to the spine to introduce a new surgical technique as a viable and less invasive alternative to standard posterior (PLIF) or transforaminal (TLIF) lumbar interbody fusion techniques : For certain indications clinical data show that unilateral lumbar interbody fusion (ULIF) offers the surgeon a considerable time advantage compared to standard lumbar interbody fusion techniques. PMID- 27682305 TI - Effectiveness and safety of collagenase Clostridium histolyticum in Dupuytren's disease : an observational study in Belgium. AB - Dupuytren's disease is a connective tissue disorder leading to contractures. It can be treated surgically or through injections of collagenase Clostridium histolyticum (CCH). Patients with Dupuytren's contracture (> 20 degrees ) and a palpable cord were included in this observational study, aiming to characterise the Belgian patient population and to assess the effectiveness and safety of CCH. Overall, 108 patients (114 joints) received at least one injection of CCH, and 104 patients completed the study. The percentages of joints achieving a degree of contracture of 5 degrees or less, or a relative contracture reduction of at least 50% after the extension procedure were 64.9% and 90.1%, respectively. The mean number of injections per cord was 1.0. The Unite Rhumatologique des Affections de la Main score decreased from 29.4 +/- 11.0 to 12.9 +/- 6.3 (mean +/ SD ; p < 0.0001). CCH was demonstrated to be effective, safe and able to increase quality of life. PMID- 27682308 TI - Combination of transpedicular enucleation and Plate-Rod System for single-stage correction of progressive hemivertebral scoliosis. AB - The purpose of this study is to report the effectiveness of transpedicular enucleation and Plate-Rod System for Scoliosis (PRSS) fixation for the treatment of hemivertebral (HV) scoliosis. 16 patients with progressive HV scoliosis underwent the combined procedure. The technique involves excision of cancellous bone to eliminate the blood supply of the cartilaginous endplate and destroy the superior and inferior vertebral end plates, followed by PRSS fixation to correct the main curve and compensatory curve. The mean age at operation was 8.125 +/- 1.82 years. The scoliosis curve was corrected from average 55.06 +/- 25.68 degrees preoperatively to 21.25 +/- 15.51 degrees postoperatively. At the latest follow-up, the Cobb angle was 24.38 +/- 16.44 degrees , and there was no significant -difference compared with immediate postoperative angle (P > 0.05). No surgical complication of neurological deficits occurred in any patients. Combined use of transpedicular enucleation and PRSS fixation is a safe and effective single-stage method for the management of HV scoliosis in growing children. PMID- 27682309 TI - Synthesis of a Sterically Demanding Dispiropiperidine and Its Application in Monoamidodialkyl Zincate Complexes. AB - The new sterically hindered piperidine analog, dispiro[cyclohexane-2,2' piperidine-6',2"-cyclohexane] (CPC(H), 2), and its N-methylated derivative CPC(Me) (3) were synthesized from commercially available starting materials in short steps. The N-lithiated amide LiCPC (4) was also isolated from 2 as a cyclictrimer in single crystals and showed slightly larger steric hindrance than that of lithium 2,2,6,6-tetramethylpiperidide (LiTMP) in the competitive methylation reaction with methyl trifluoromethanesulfonate. In addition, the heterobimetallic heteroleptic zincate complexes [Li(MU-NR2)(MU-Et)Zn(Et)] (NR2 = CPC, 5, and NR2 = TMP, 6) were obtained as THF- and TMEDA-coordinated monomer 5.(THF)2, 6.(THF)2, 5.TMEDA, and 6.TMEDA (THF = tetrahydrofuran, TMEDA = N,N,N',N'-tetramethylethylenediamine). These molecular structures bearing different amido ligands in single crystals showed little structural differences from crystallographic studies. Diffusion-ordered spectroscopy (DOSY) revealed that the solution structures of the zincate complexes 5.(THF)2 and 6.(THF)2 only differ in the number of coordination THF molecules. In the deprotonation reactions with tert-butyl 3-bromobenzoate, the zincate complexes containing the CPC ligand [Li(MU-CPC)(MU-R)Zn(R)] (R = Et (5), tBu) showed moderately improved regioselectivity for the 6 position in comparison to those containing the TMP ligand [Li(MU-TMP)(MU-R)Zn(R)] (R = Et (6), tBu). PMID- 27682310 TI - Synthesis of 5-Iodo-1,2,3,4-tetrahydropyridines by Rhodium-Catalyzed Tandem Nucleophilic Attacks Involving 1-Sulfonyl-1,2,3-triazoles and Iodides. AB - Sodium iodide is used for the first time as a nucleophile to trap an alpha-imino rhodium carbene, which triggers a tandem process involving intermolecular nucleophilic attack and intramolecular SN2 reaction. A series of 5-iodo-1,2,3,4 tetrahydropyridines are obtained in high yield, and the synthetic utility of the products is demonstrated in cross-coupling reactions and the construction of biorelated polycyclic compounds. PMID- 27682311 TI - Calculating Exclusive Breastfeeding Rates: Comparing Dietary "24-Hour Recall" with Recall "Since Birth" Methods. AB - BACKGROUND: Calculating exclusive breastfeeding (EBF) rates based on the previous day recall has been recommended by the World Health Organization to avoid the recall bias but it also may not accurately reflect the feeding pattern since birth and leads to overestimate of the proportion of exclusively breastfed infants. The objective of this study was to compare the (EBF) rates calculated by the 24-hour recall and since birth recall and their association with different sociodemographic and maternal data. SUBJECTS AND METHODS: Prospective descriptive study in Mansoura District including 1,102 mother-infant dyad attending primary healthcare centers for vaccination. One thousand ninety-one and 1,029 were followed up at 4 and 6 months during a period from January to October 2015. Sociodemographic data, maternal, antenatal, birth, and some infant related data were collected through interview. Questions about EBF using the 24-hour recall and since birth recall definitions were asked. RESULTS: This study shows consistent difference in breastfeeding pattern reported by 24-hour recall with recall since birth at all age intervals. At the age of 6 months 13.6% of infants were EBF as reported by 24-hour recall method versus 5.2% for recall since birth method. Different factors were associated with EBF practice reported using these different methods. CONCLUSIONS: The two recall methods describe the reality in different and incomplete ways. It is better to measure and report EBF rated using both methods so as to give a full picture of breastfeeding practice. And it is very important to distinguish between both methods and not to be used interchangeably with each other. PMID- 27682313 TI - 125 Iodine brachytherapy via a trans-superior vena cava approach in patients with metastases in middle mediastinal lymph nodes: a novel approach. AB - AIM: Certain metastasis-containing middle mediastinal lymph nodes cannot be approached by standard CT-guided brachytherapy. We here describe a novel trans superior vena cava approach for such nodes. The aim of this prospective study was to assess the safety and clinical value of 125 iodine (I) brachytherapy via a trans-superior vena cava approach in patients with metastases in middle mediastinal lymph nodes. METHODS: From February 2008 to October 2011, 32 patients with 43 pathologically confirmed metastasis-containing mediastinal middle lymph nodes underwent CT-guided percutaneous 125 I brachytherapy via a trans-superior vena cava approach. Their complications and treatment responses were analyzed. Variations in blood pressure, heart rate, hemoglobin concentration and oxyhemoglobin saturation before, during and after the procedure were recorded, as were complications, including hemorrhage, pneumothorax and development of Breuer's reflex. Treatment response was assessed according to the response evaluation criteria for solid tumors Version 1.1. RESULTS: According to follow-up CT examination after 6 months, 22 patients (68.75%) achieved complete responses and four (12. 5%) partial responses. One patient died of myocardial infarction. Overall response rate was 81.25%, with a local control rate of 87.5%. The median survival was 25.7 months, with progression-free survival of 19.74 +/- 0.81 months. The 1-year and 3-year overall survival rates were 53.13% and 28.13%. There were minimal immediate or delayed complications; no complications were severe. CONCLUSION: We consider this novel approach a safe means of treating certain mediastinal middle lymph node metastases. PMID- 27682312 TI - Diagnostic accuracy of coronary CT angiography using 3rd-generation dual-source CT and automated tube voltage selection: Clinical application in a non-obese and obese patient population. AB - PURPOSE: To investigate diagnostic accuracy of 3rd-generation dual-source CT (DSCT) coronary angiography in obese and non-obese patients. METHODS: We retrospectively analyzed 76 patients who underwent coronary CT angiography (CCTA) and invasive coronary angiography. Prospectively ECG-triggered acquisition was performed with automated tube voltage selection (ATVS). Patients were dichotomized based on body mass index in groups A (<30 kg/m2, n = 37) and B (>=30 kg/m2, n = 39) and based on tube voltage in groups C (<120 kV, n = 46) and D (120 kV, n = 30). Coronary arteries were assessed for significant stenoses (>=50 % luminal narrowing) and diagnostic accuracy was calculated. RESULTS: Per-patient overall sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy were 96.9 %, 95.5 %, 93.9 %, 97.7 % and 96.1 %, respectively. Sensitivity and NPV were lower in groups B and D compared to groups A and C, but no statistically significant differences were observed (group A vs. B: sensitivity, 100.0 % vs. 93.3 %, p = 0.9493; NPV, 100 % vs. 95.5 %, p = 0.9812; group C vs. D: sensitivity, 100.0 % vs. 92.3 %, p = 0.8462; NPV, 100.0 % vs. 94.1 %, p = 0.8285). CONCLUSION: CCTA using 3rd-generation DSCT and (ATVS) provides high diagnostic accuracy in both non-obese and obese patients. KEY POINTS: * Coronary CTA provides high diagnostic accuracy in non-obese and obese patients. * Diagnostic accuracy between obese and non-obese patients showed no significant difference. * <120 kV studies were performed in 44 % of obese patients. * Current radiation dose-saving approaches can be applied independent of body habitus. PMID- 27682314 TI - Temporal efficiency evaluation and small-worldness characterization in temporal networks. AB - Numerous real-world systems can be modeled as networks. To date, most network studies have been conducted assuming stationary network characteristics. Many systems, however, undergo topological changes over time. Temporal networks, which incorporate time into conventional network models, are therefore more accurate representations of such dynamic systems. Here, we introduce a novel generalized analytical framework for temporal networks, which enables 1) robust evaluation of the efficiency of temporal information exchange using two new network metrics and 2) quantitative inspection of the temporal small-worldness. Specifically, we define new robust temporal network efficiency measures by incorporating the time dependency of temporal distance. We propose a temporal regular network model, and based on this plus the redefined temporal efficiency metrics and widely used temporal random network models, we introduce a quantitative approach for identifying temporal small-world architectures (featuring high temporal network efficiency both globally and locally). In addition, within this framework, we can uncover network-specific dynamic structures. Applications to brain networks, international trade networks, and social networks reveal prominent temporal small world properties with distinct dynamic network structures. We believe that the framework can provide further insight into dynamic changes in the network topology of various real-world systems and significantly promote research on temporal networks. PMID- 27682316 TI - Antibacterial effects of volatiles produced by Bacillus strain D13 against Xanthomonas oryzae pv. oryzae. AB - Recent investigations have demonstrated that bacteria employ the volatile compounds they produce during interactions with other organisms, such as plants, fungi, nematodes and bacteria. However, studies focused on the antibacterial activity of plant growth-promoting rhizobacteria (PGPR) volatiles against bacterial phytopathogens are still rare. In this study, Bacillus strain D13, which is antagonistic to Xanthomonas oryzae pv. oryzae (Xoo), was isolated and screened. Volatile compounds emitted from strain D13 reduced the colony diameter and cell motility of Xoo cultured in divided Petri plates. Transmission electron micrograph analysis showed concentration in cytoplasm and altered surface morphology in the majority of Xanthomonas cells after co-cultivation with strain D13. Transcriptional expression of virulence-associated genes in Xoo was repressed. Based on gas chromatography/mass spectrometry (GC/MS) analysis, 12 volatile compounds specifically produced by strain D13 were identified. Among them, decyl alcohol and 3,5,5-trimethylhexanol inhibited the growth of Xoo at minimum inhibitory amounts of 0.48 and 2.4 mg, respectively. Furthermore, transcriptional expression of virulence-associated genes was also repressed by decyl alcohol and 3,5,5-trimethylhexanol. These results are useful for a better understanding of the biocontrol mechanisms of Bacillus. PMID- 27682315 TI - One-year Surveillance of Human Enteric Viruses in Raw and Treated Wastewaters, Downstream River Waters, and Drinking Waters. AB - Human enteric viruses are a major cause of waterborne diseases, and can be transmitted by contaminated water of all kinds, including drinking and recreational water. The objectives of the present study were to assess the occurrence of enteric viruses (enterovirus, norovirus, adenovirus, hepatitis A and E virus) in raw and treated wastewaters, in rivers receiving wastewater discharges, and in drinking waters. Wastewater treatment plants' (WWTP) pathogen removal efficiencies by adenovirus quantitative real-time PCR and the presence of infectious enterovirus, by cell culture assays, in treated wastewaters and in surface waters were also evaluated. A total of 90 water samples were collected: raw and treated wastewaters (treated effluents and ultrafiltered water reused for industrial purposes), water from two rivers receiving treated discharges, and drinking water. Nested PCR assays were used for the identification of viral DNA/RNA, followed by direct amplicon sequencing. All raw sewage samples (21/21), 61.9 % of treated wastewater samples (13/21), and 25 % of ultrafiltered water samples (3/12) were contaminated with at least one viral family. Multiple virus families and genera were frequently detected. Mean positive PCRs per sample decreased significantly from raw to treated sewage and to ultrafiltered waters. Moreover, quantitative adenovirus data showed a reduction in excess of 99 % in viral genome copies following wastewater treatment. In surface waters, 78.6 % (22/28) of samples tested positive for one or more viruses by molecular methods, but enterovirus-specific infectivity assays did not reveal infectious particles in these samples. All drinking water samples tested negative for all viruses, demonstrating the effectiveness of treatment in removing viral pathogens from drinking water. Integrated strategies to manage water from all sources are crucial to ensure water quality. PMID- 27682317 TI - Morphological and ultrastructural studies of human spermatogonial stem cells from patients with maturation arrest. AB - Destruction of spermatogonial stem cells (SSCs) along the chemotherapy and radiotherapy is one of the side effects of cancer treatments that lead to infertility. In vitro propagation of hSSCs is necessary to obtain an adequate number of cells for successful transplantation. In this study, hSSCs were isolated from testis biopsies of the patients with maturation arrest and proliferated in DMEM in the presence of LIF and bFGF for 5 weeks. The various types of human spermatogonia were identified in culture system and compared with testis tissue using morphological criteria at the ultrastructural level. The results showed that although many various types of spermatogonia were identified, but no remarkable difference was observed between spermatogonial cells in culture system and testis tissue. Electron and light microscopic studies of hSSC colonies did not show differentiated SSCs in the culture system. The results also showed that probably the suitable time for transplanting of SSCs in recipient testis is 2-3 weeks after culture. Because apoptosis which may affect the development of germ cells has not started in colony cells at this time and the population of apoptotic cells are low. PMID- 27682318 TI - Nitroxyl-Radical-Catalyzed Oxidative Coupling of Amides with Silylated Nucleophiles through N-Halogenation. AB - A nitroxyl-radical-catalyzed oxidative coupling reaction between amines with an N protecting electron-withdrawing group (EWG) and silylated nucleophiles was developed to furnish coupling products in high yields, thus opening up new frontiers in organocatalyzed reactions. This reaction proceeded through the activation of N-halogenated amides by a nitroxyl-radical catalyst, followed by carbon-carbon coupling with silylated nucleophiles. Studies of the reaction mechanism indicated that the nitroxyl radical activates N-halogenated amides, which are generated from N-EWG-protected amides and a halogenation reagent, to give the corresponding imines. PMID- 27682319 TI - Incidence of early childhood caries: A systematic review and meta-analysis. AB - The aim was to systemically review the incidence of early childhood caries (ECC). The addressed focused question was "What is the reported incidence of ECC?" Indexed databases were searched using various key words. Five studies were included and processed for data extraction. All studies were prospective and two studies were randomized clinical trials. The number of participants ranged between 96 and 1275 children. Two studies reported the mean age of children, that ranged between 1.8 and 2.5 years (range 0.5 to 5 years). In three studies, the follow-up duration was 2 years, and in two studies the participants were followed up till 3 and 5 years, respectively. Results from all studies reported that the incidence of ECC was significantly higher among children with caries at baseline compared with caries-free children. In conclusion, the incidence of ECC is significantly higher in children with a previous history of dental caries. PMID- 27682321 TI - Molecular pharmacology of G protein-coupled receptors. AB - This themed issue of the British Journal of Pharmacology stems from the eighth in the series of meetings on the Molecular Pharmacology of G protein coupled receptors (MPGPCR) held as part of a joint meeting with the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) in Melbourne Australia from 7 to 11 December 2014. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc. PMID- 27682320 TI - Effects of early life stress on depression, cognitive performance and brain morphology. AB - BACKGROUND: Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure. METHOD: This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus. RESULTS: Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects. CONCLUSIONS: Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression. PMID- 27682322 TI - Comparative pharmacokinetics of minocycline in foals and adult horses. AB - The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6- to 9-week old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells. After i.v. administration to foals, minocycline had a mean (+/-SD) elimination half-life of 8.5 +/- 2.1 h, a systemic clearance of 113.3 +/- 26.1 mL/h/kg, and an apparent volume of distribution of 1.24 +/- 0.19 L/kg. Pharmacokinetic variables determined after i.v. administration to adult horses were not significantly different from those determined in foals. Bioavailability was significantly higher in foals (57.8 +/- 19.3%) than in adult horses (32.0 +/- 18.0%). Minocycline concentrations in PELF were higher than in other body fluids. Oral minocycline dosed at 4 mg/kg every 12 h might be adequate for the treatment of susceptible bacterial infections in foals. PMID- 27682323 TI - Using Pseudomonas aeruginosa PAO1 to evaluate hydrogen peroxide as a biofouling control agent in membrane treatment systems. AB - : Hydrogen peroxide (H2 O2 ) is widely used in water treatment for biofouling control and, in conjunction with catalysts, as a powerful oxidant for contaminant destruction. H2 O2 could potentially serve as an antifouling agent in reverse osmosis systems in lieu of chlorine-based disinfectants. The dependence of the biocidal efficiency of H2 O2 on cell density, temperature and H2 O2 concentration by determining the growth, attachment and viability of the model bacterium Pseudomonas aeruginosa PAO1 was studied. For controlling growth of planktonic PAO1 cells, the minimally required H2 O2 concentration depends on the cell density and temperature. The effect of H2 O2 to remove the existing biofilm was found to be effective in the presence of a high concentration bicarbonate (8.4 g l-1 ), which forms peroxymonocarbonate, a strong oxidant and disinfectant. Treatment with H2 O2 -bicarbonate reduced the density of live PAO1 cells, removed extracellular polymeric substances and lowered the average biofilm thickness while maintaining the integrity of the membrane, suggesting that this type of treatment may be a suitable 'in-place-cleaning' procedure for biofouled membranes. SIGNIFICANCE AND IMPACT OF THE STUDY: H2 O2 is evaluated as a potential replacement for chlorine to control biofouling in membrane-based water treatment systems. The biocidal efficacy of H2 O2 was evaluated as a function of H2 O2 concentration, cell density and temperature using the model organism Pseudomonas aeruginosa PAO1. Results demonstrated that at low temperatures and low cell densities, bacterial growth and membrane biofouling can be prevented by low H2 O2 concentrations, and existing biofilms could be removed by H2 O2 bicarbonate mixtures. Findings suggested that H2 O2 could be used as a low cost agent for prevention and controlling biofouling in reverse osmosis applications. PMID- 27682324 TI - Trends in Incidence of Disability in Activities of Daily Living in Chinese Older Adults: 1993-2006. AB - OBJECTIVES: To investigate time trends in incidence of activity of daily living (ADL) disability of Chinese older adults and to explore factors potentially contributing to trends. DESIGN: Population-based prospective study using a multistage, randomized, cluster sampling process. SETTING: Nine provinces of China. PARTICIPANTS: Three consecutive cohorts of people aged 60 and older from the China Health and Nutrition Survey: cohort 1993-2000 (n = 831), cohort 1997 2004 (n = 1,091), cohort 2000-2006 (n = 1,152). MEASUREMENTS: Disability in ADLs was defined as inability to perform at least one of five self-care activities (transferring, dressing, toileting, bathing, feeding). Data were analyzed using Cox and generalized estimating equation models. RESULTS: The incidence (per 1,000 person-years) of ADL disability decreased significantly from 35.3 in 1993-2000 and 28.9 in 1997-2004 to 24.3 in 2000-2006 in Chinese older adults (Ptrend < .001). The incidence of ADL disability decreased significantly in men and women, in young-old adults (aged 60-74), and in those living in rural areas (all Ptrend <= .02) after controlling for multiple potential influential factors. Of the five ADL items, decline in incidence of disability was significant in transferring (Ptrend < .001) and bathing (Ptrend = .002) and marginally significant in toileting (Ptrend = .06) but stable in dressing (Ptrend = .38) and feeding (Ptrend = .26). CONCLUSION: The incidence of ADL disability decreased from 1993 to 2006 in older adults in China, especially in transferring and bathing, independent of sociodemographic, lifestyle, and chronic health conditions. PMID- 27682326 TI - Familial Horizontal Gaze Palsy With Progressive Scoliosis. PMID- 27682325 TI - Differences between serum polar lipid profiles of male and female rheumatoid arthritis patients in response to glucocorticoid treatment. AB - OBJECTIVE: As there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients. METHODS: Serum samples from 281 RA patients were analysed using a targeted lipidomics platform. The differences in GC use and gender on polar lipid profiles were cross sectionally examined by multiple linear regressions, while correcting for confounding factors. RESULTS: Differences in polar lipids between GC users and non-GC users in females and males were merely restricted to lysophospholipids (lysophosphatidylcholines and lysophosphatidylethanolamines). Lysophospholipids in female patients treated with GCs were significantly higher than female patients not treated with GCs (p = 6.0 E-6), whereas no significant difference was observed in male GC users versus non users (p = 0.397). CONCLUSION: The lysophospholipid profiles in response to GCs were significantly different between male and female RA patients, which may have implications for the cardiovascular risk of GC treatment. PMID- 27682327 TI - Long-term clinical outcomes of 'Prairie Epidemic Strain' Pseudomonas aeruginosa infection in adults with cystic fibrosis. AB - RATIONALE: Epidemic Pseudomonas aeruginosa (PA) plays an important role in cystic fibrosis (CF) lung disease. A novel strain, the 'Prairie Epidemic Strain' (PES), has been identified in up to 30% of patients in Prairie-based Canadian CF centres. OBJECTIVE: To determine the incidence, prevalence and long-term clinical impact of PES infection. METHODS: A cohort of adults with CF was followed from 1980 to 2014 where bacteria isolated from clinical encounters were prospectively collected. Strain typing was performed using pulse-field gel electrophoresis and multilocus sequence typing. Patients were divided into one of four cohorts: no PA, transient PA, chronic PA with unique strains and chronic PES. Proportional Cox hazard and linear mixed models were used to assess for CF-associated respiratory death or transplantation, and rates of %FEV1 and body mass index (BMI) decline. RESULTS: 274 patients (51.7% male) were analysed: 44--no PA, 29- transient PA, 137--unique PA, 64--PES. A total of 92 patients (33.6%) died or underwent lung transplantation (2423.0 patient-years). PES infection was associated with greater risk of respiratory death or lung transplant compared with the no PA group (aHR, 3.94 (95% CI 1.18 to 13.1); p=0.03) and unique PA group (aHR, 1.75 (95% CI 1.05 to 2.92) p=0.03). Rate of lung function decline (%FEV1 predicted) was greatest in the PES group (1.73%/year (95% CI 1.63% to 1.82%); p<0.001). BMI improved over time but at an attenuated rate in the PES group (p=0.001). CONCLUSIONS: Infection with PES was associated with increased patient morbidity through three decades and manifested in an increased risk of respiratory death and/or lung transplantation. PMID- 27682328 TI - Pulmonary endarterectomy for calcified amorphous tumour-related pulmonary hypertension. PMID- 27682329 TI - Large airways nodularity secondary to tracheobronchopathia osteochondroplastica. PMID- 27682332 TI - Molecular-Thermodynamic Modeling of Mixed Cationic/Anionic Vesicles. AB - Vesicles are widely used as model cells in biology and medicine and are also potentially useful as drug carriers and other industrial encapsulating devices. To facilitate the practical implementation of vesicles, as well as to gain a fundamental understanding of the process of vesicle formation, we have developed a molecular-thermodynamic theory to describe the formation of two-component mixed vesicles in aqueous solutions. The central quantity in this theory is the free energy of vesiculation, which is calculated by carefully modeling the various free-energy contributions to vesiculation. In particular, we (i) estimate the surfactant-tail packing free energy using a mean-field approach that accounts for the conformations of the surfactant tails in the vesicle hydrophobic region, (ii) adopt a more accurate equation of state in the calculation of the surfactant-head steric repulsions, and (iii) utilize the nonlinear Poisson-Boltzmann equation to calculate the electrostatic interactions in the case of mixed cationic/anionic charged vesicles. Particular attention has also been paid to issues such as the location of the outer and inner steric-repulsion surfaces in a vesicle and the curvature correction to the interfacial tensions at the outer and inner hydrocarbon/water vesicle interfaces. By knowing only the molecular structures of the surfactants involved in vesicle formation and the solution conditions, our theory can predict a wealth of vesicle properties, including vesicle size and composition distribution, surface potentials, surface charge densities, and compositions of vesicle leaflets. More importantly, this theory enables us to gain an understanding of (i) the underlying mechanisms of stabilization in mixed cationic/anionic vesicular systems, (ii) the effect of the interplay between the various intravesicular free-energy contributions on vesiculation, and (iii) the role of the distribution of surfactant molecules between the two vesicle leaflets in vesicle formation. As an illustration, the theory has been applied to describe vesicle formation in an aqueous mixture of cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS). In this system, the vesicles are found to be stabilized entropically, with a predicted mean radius of about 1200 A for a mixture containing 2 wt % surfactant and a CTAB/SOS weight ratio of 3/7, a value which compares well with the experimentally measured value of 1300 A. In addition, the predicted outer surface potential of -72 mV is consistent with the measured zeta potential value. The effect of added salt on vesicle properties has also been studied using this theory, and the predicted results conform well to experimental observations. PMID- 27682334 TI - Portuguese validation of the Short Health Anxiety Inventory: Factor structure, reliability, and factor invariance. AB - The Short Health Anxiety Inventory is a brief instrument to assess health anxiety widely used across countries; however, no validated version is available for Portuguese-speaking population. Factorial structure, reliability, and equivalency factor with the Spanish version were analyzed with Portuguese adolescents aged 14 18 years. A Portuguese adolescent cohort ( N = 629) and a comparative Spanish adolescent cohort ( N = 1502) were evaluated. The original two-factor version was the best fitting model for the Portuguese version. The reliability was excellent. Complete measurement invariance across both countries was supported. The Portuguese version of the Short Health Anxiety Inventory is a valid screening inventory to assess health anxiety in adolescents. PMID- 27682333 TI - The Effect of n vs. iso Isomerization on the Thermophysical Properties of Aromatic and Non-aromatic Ionic Liquids. AB - This work explores the n vs. iso isomerization effects on the physicochemical properties of different families of ionic liquids (ILs) with variable aromaticity and ring size. This study comprises the experimental measurements, in a wide temperature range, of the ILs' thermal behavior, heat capacities, densities, refractive indices, surface tensions, and viscosities. The results here reported show that the presence of the iso-alkyl group leads to an increase of the temperature of the glass transition, Tg. The iso-pyrrolidinium (5 atoms ring cation core) and iso-piperidinium (6 atoms ring cation core) ILs present a strong differentiation in the enthalpy and entropy of melting. Non-aromatic ILs have higher molar heat capacities due to the increase of the atomic contribution, whereas it was not found any significant differentiation between the n and iso alkyl isomers. A small increase of the surface tension was observed for the non aromatic ILs, which could be related to their higher cohesive energy of the bulk, while the lower surface entropy observed for the iso isomers indicates a structural resemblance between the IL bulk and surface. The significant differentiation between ILs with a 5 and 6 atoms ring cation in the n-alkyl series (where 5 atoms ring cations have higher surface entropy) is an indication of a more efficient arrangement of the non-polar region at the surface in ILs with smaller cation cores. The ILs constituted by non-aromatic piperidinium cation, and iso-alkyl isomers were found to be the most viscous among the studied ILs due to their higher energy barriers for shear stress. PMID- 27682335 TI - Exploring breast health practices of post-menopausal women: Implications to informed consent. AB - In light of the contention surrounding breast health practices, the research aimed to explore post-menopausal women's experiences of such practices. Semi structured interviews were conducted in July and August 2015 with 13 Australian women aged 54-74 years. Data were analysed thematically. Participants deemed their engagement with breast health practices as the 'right' thing. However, engaging in these 'right' practices appeared to be fostered by misconceptions. The findings suggest that women may not be making evidence-informed decisions to engage in breast screening; identify contemporary barriers to promoting informed decisions; and may inform information pertinent to breast screening policy, campaigns and decision aid designs. PMID- 27682331 TI - Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial. AB - BACKGROUND: Physiotherapy, and speech and language therapy are emerging non pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. METHODS: In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). FINDINGS: Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. INTERPRETATION: Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. TRIAL REGISTRATION NUMBER: UKCRN ID 10678 and ISRCTN 73039760; Results. PMID- 27682330 TI - Socio-economic inequalities in stage at diagnosis, and in time intervals on the lung cancer pathway from first symptom to treatment: systematic review and meta analysis. AB - : Cancer diagnosis at an early stage increases the chance of curative treatment and of survival. It has been suggested that delays on the pathway from first symptom to diagnosis and treatment may be socio-economically patterned, and contribute to socio-economic differences in receipt of treatment and in cancer survival. This review aimed to assess the published evidence for socio-economic inequalities in stage at diagnosis of lung cancer, and in the length of time spent on the lung cancer pathway. MEDLINE, EMBASE and CINAHL databases were searched to locate cohort studies of adults with a primary diagnosis of lung cancer, where the outcome was stage at diagnosis or the length of time spent within an interval on the care pathway, or a suitable proxy measure, analysed according to a measure of socio-economic position. Meta-analysis was undertaken when there were studies available with suitable data. Of the 461 records screened, 39 papers were included in the review (20 from the UK) and seven in a final meta-analysis for stage at diagnosis. There was no evidence of socio economic inequalities in late stage at diagnosis in the most, compared with the least, deprived group (OR=1.04, 95% CI=0.92 to 1.19). No socio-economic inequalities in the patient interval or in time from diagnosis to treatment were found. Socio-economic inequalities in stage at diagnosis are thought to be an important explanatory factor for survival inequalities in cancer. However, socio economic inequalities in stage at diagnosis were not found in a meta-analysis for lung cancer. PROSPERO PROTOCOL REGISTRATION NUMBER: CRD42014007145. PMID- 27682337 TI - Listening to both sides: A qualitative comparison between patients with hepatitis C and their healthcare professionals' perceptions of the facilitators and barriers to hepatitis C treatment adherence and completion. AB - This qualitative study compares and contrasts the perspectives of healthcare professionals who treat hepatitis C with those of patients in treatment. Comparative analysis of semi-structured interviews with 20 healthcare professionals and 20 patients undergoing treatment for hepatitis C concluded that patients and healthcare professionals disagreed on the source of communication breakdowns, but both felt that individualised clinical information improved adherence. Stigma was recognised as a barrier to treatment adherence by both patients and healthcare professionals. Limitations of the healthcare system, such as patients receiving inconsistent information and long wait times, negatively impacted both patients and providers. PMID- 27682336 TI - Nutritionism and the construction of 'poor choices' in families facing food insecurity. AB - The dominant research approach to both food insecurity and charitable meal provision is nutritionistic, deficit-orientated and ignores wider socio-economic issues. This reinforces existing power dynamics and overlooks the agency of people living food-insecure lives. We critique this dominant approach and draw on the everyday experiences of families facing food insecurity to ground an alternative approach that emphasises food as a social determinant of health. PMID- 27682338 TI - Locus of control and pain: Validity of the Form C of the Multidimensional Health Locus of Control scales when used with adolescents. AB - The objective of this study was to examine the factor structure, reliability, and validity of the Form C of the Multidimensional Health Locus of Control scales in adolescents. A confirmatory factor analysis indicated that adequate fit of a four factor model and the internal consistency of the scales were adequate. Criterion validity of the four scales of the Form C of the Multidimensional Health Locus of Control was also supported by significant correlations with measures of pain related self-efficacy, anxiety, and coping strategies. The results indicate that the four Form C of the Multidimensional Health Locus of Control scale scores are reliable and valid and therefore support their use to assess pain-related locus of control beliefs in adolescents. PMID- 27682339 TI - A qualitative exploration of the daily experiences and challenges faced by parents and caregivers of children with Tourette's syndrome. AB - Few studies address the daily challenges faced by parents of children diagnosed with Tourette's syndrome. This article reports on a qualitative interview study with 15 parents exploring their experiences, the challenges they face and the support mechanisms they have found to be most helpful. Thematic analysis identified four core categories which represented shared experiences of the participants: coping with children's challenging behaviours, misconceptions and lack of understanding of professionals and the lay public, negative experiences of their children's education and lack of support and services for families with Tourette's syndrome. The findings highlight the challenges of parenting a child with Tourette's syndrome, particularly with respect to family life and the child's schooling. PMID- 27682340 TI - Taking a hard look at the Heart Truth campaign in Canada: A discourse analysis. AB - The Canadian Heart and Stroke Foundation launched the Heart Truth campaign to increase women's awareness of heart disease. However, little is known about how such campaigns intersect with broader understandings of gender and health. This discourse analysis examined the construction of gender, risk, and prevention within campaign material. Two primary discourses emerged: one of acceptable femininity, which outlines whose risk, survivorship, and prevention matters, and another of selfless prevention. Women of diverse ethnic, sexual, and socio economic background were largely absent. Prevention was portrayed as a personal choice, eclipsing conversations about social determinants of health and the socio political context of heart disease. PMID- 27682341 TI - A qualitative content analysis of peer mentoring video calls in adolescents with chronic illness. AB - This article endeavored to determine the topics of discussion during open-ended peer mentoring between adolescents and young adults living with chronic illness. This study occurred alongside a study of the iPeer2Peer Program. Fifty-two calls (7 mentor-mentee pairings) were audio recorded, transcribed verbatim, and analyzed using inductive coding with an additional 30 calls (21 mentor-mentee pairings) coded to ensure representativeness of the data. Three categories emerged: (1) illness impact (e.g., relationships, school/work, self-identity, personal stories), (2) self-management (e.g., treatment adherence, transition to adult care, coping strategies), and (3) non-illness-related adolescent issues (e.g., post-secondary goals, hobbies, social environments). Differences in discussed topics were noted between sexes and by diagnosis. Peer mentors provided informational, appraisal, and emotional support to adolescents. PMID- 27682342 TI - Visible Light Photocatalysis for the Generation and Use of Reactive Azolyl and Polyfluoroaryl Intermediates. AB - Photocatalysis offers several mechanistically unique pathways that are not rivaled by mainstream catalysis. Primarily, the ability to convert photochemical energy into single electron oxidation and reduction events provides a new dimension for chemists to consider when choosing how to activate a molecule or approach a complex synthesis. Since most organic molecules do not absorb light in the visible region, they are impervious to direct visible light photochemistry, which provides an opportunity for photocatalysis in which a visible light absorbing compound can serve as a mediator. In this Account, we discuss the consequences of catalyst mediated, photoinduced electron transfer to several classes of reducible arenes. While the bulk of the work discussed within this Account utilizes iridium-based photocatalysts, in principle the chemistry is not limited to this class of photocatalyst, and the principles should be more general. Instead, this Account focuses largely on the consequences of single electron transfer to poly- and perfluorinated arenes and 2-halo azoles. Electron transfer converts these stable molecules into reactive intermediates whose behavior often depends entirely on the identity of the halogen that undergoes substitution. The result is both diverse chemistry and an alternative way of thinking about the chemical reactivity of these motifs. Specifically, we discuss our efforts and those of others to develop strategies for the generation of radicals or radical anions from perfluoroarenes and azoles and the behavior of these intermediates as implied by reactions in which they participate. The divergent pathway is illustrated by 2-bromoazoles, which yield azolyl radicals and can be utilized for addition to pi-bonds, while use of the 2-chloroazole substrate leads to an entirely different reaction profile. Under the appropriate reaction conditions, the reactive and transient intermediates are useful coupling partners and often provide unrivaled access to new chemical space. The odd electron species can form challenging bonds with minimal prefunctionalization of the coupling partner. For instance, some of the intermediates can be utilized for C-H functionalizations to selectively make crowded amines or to synthesize biarenes substituted at every ortho position. While photocatalysis is not the only manner of accomplishing electron transfer, the catalytic generation of the reactive species in which the concentration of the transient odd electron species is kept low, provides a synthetic handle that can be used to improve reaction outcomes. This is elegantly demonstrated in a number of examples in which redox sensitive groups located on substrates survive the reaction. In addition, the underlying basic concepts associated with radical anion fragmentation are reviewed and provide the backdrop for discussion throughout the Account. PMID- 27682343 TI - Five minutes with . . . John Ioannidis. PMID- 27682344 TI - Pathways for Arene Oxidation in Non-Heme Diiron Enzymes: Lessons from Computational Studies on Benzoyl Coenzyme A Epoxidase. AB - Oxygenation of aromatic rings using O2 is catalyzed by several non-heme carboxylate-bridged diiron enzymes. In order to provide a general mechanistic description for these reactions, computational studies were carried out at the ONIOM(B3LYP/BP86/Amber) level on the non-heme diiron enzyme benzoyl coenzyme A epoxidase, BoxB. The calculations revealed four possible pathways for attacking the aromatic ring: (a) electrophilic (2e-) attack by a bis(MU-oxo)-diiron(IV) species (Q pathway); (b) electrophilic (2e-) attack via the sigma* orbital of a MU-eta2:eta2-peroxo-diiron(III) intermediate (Psigma* pathway); (c) radical (1e-) attack via the pi*-orbital of a superoxo-diiron(II,III) species (Ppi* pathway); (d) radical (1e-) attack of a partially quenched bis(MU-oxo)-diiron(IV) intermediate (Q' pathway). The results allowed earlier work of de Visser on olefin epoxidation by diiron complexes and QM-cluster studies of Liao and Siegbahn on BoxB to be put into a broader perspective. Parallels with epoxidation using organic peracids were also examined. Specifically for the BoxB enzyme, the Q pathway was found to be the most preferred, but the corresponding bis(MU-oxo) diiron(IV) species is significantly destabilized and not expected to be directly observable. Epoxidation via the Psigma* pathway represents an energetically somewhat higher lying alternative; possible strategies for experimental discrimination are discussed. The selectivity toward epoxidation is shown to stem from a combination of inherent electronic properties of the thioacyl substituent and enzymatic constraints. Possible implications of the results for toluene monooxygenases are considered as well. PMID- 27682346 TI - Why are we still detecting food-related Salmonella outbreaks in Spain? PMID- 27682345 TI - Improving the Force Field Description of Tyrosine-Choline Cation-pi Interactions: QM Investigation of Phenol-N(Me)4+ Interactions. AB - Cation-pi interactions between tyrosine amino acids and compounds containing N,N,N-trimethylethanolammonium (N(CH3)3) are involved in the recognition of histone tails by chromodomains and in the recognition of phosphatidylcholine (PC) phospholipids by membrane-binding proteins. Yet, the lack of explicit polarization or charge transfer effects in molecular mechanics force fields raises questions about the reliability of the representation of these interactions in biomolecular simulations. Here, we investigate the nature of phenol-tetramethylammonium (TMA) interactions using quantum mechanical (QM) calculations, which we also use to evaluate the accuracy of the additive CHARMM36 and Drude polarizable force fields in modeling tyrosine-choline interactions. We show that the potential energy surface (PES) obtained using SAPT2+/aug-cc-pVDZ compares well with the large basis-set CCSD(T) PES when TMA approaches the phenol ring perpendicularly. Furthermore, the SAPT energy decomposition reveals comparable contributions from electrostatics and dispersion in phenol-TMA interactions. We then compared the SAPT2+/aug-cc-pVDZ PES obtained along various approach directions to the corresponding PES obtained with CHARMM, and we show that the force field accurately reproduces the minimum distances while the interaction energies are underestimated. The use of the Drude polarizable force field significantly improves the interaction energies but decreases the agreement on distances at energy minima. The best agreement between force field and QM PES is obtained by modifying the Lennard-Jones terms for atom pairs involved in the phenol-TMA cation-pi interactions. This is further shown to improve the correlation between the occupancy of tyrosine-choline cation-pi interactions obtained from molecular dynamics simulations of a bilayer-bound bacterial phospholipase and experimental affinity data of the wild-type protein and selected mutants. PMID- 27682348 TI - Erratum to "Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites" [Int. J. Parasitol. Drugs Drug Res. 5 (2015) 117-126]. PMID- 27682349 TI - HOUSTON, WE HAVE A PROBLEM: COMMENTARY ON PREVENTION AND MANAGEMENT OF INSULIN ASSOCIATED HYPOGLYCEMIA IN HOSPITALIZED PATIENTS. PMID- 27682347 TI - Polymorphism in ion channel genes of Dirofilaria immitis: Relevant knowledge for future anthelmintic drug design. AB - Dirofilaria immitis, a filarial parasite, causes cardiopulmonary dirofilariasis in dogs, cats and wild canids. The macrocyclic lactone (ML) class of drugs has been used to prevent heartworm infection. There is confirmed ML resistance in D. immitis and thus there is an urgent need to find new anthelmintics that could prevent and/or control the disease. Targeting ion channels of D. immitis for drug design has obvious advantages. These channels, present in the nematode nervous system, control movement, feeding, mating and respond to environmental cues which are necessary for survival of the parasite. Any new drug that targets these ion channels is likely to have a motility phenotype and should act to clear the worms from the host. Many of the successful anthelmintics in the past have targeted these ion channels and receptors. Knowledge about genetic variability of the ion channel and receptor genes should be useful information for drug design as receptor polymorphism may affect responses to a drug. Such information may also be useful for anticipation of possible resistance development. A total of 224 ion channel genes/subunits have been identified in the genome of D. immitis. Whole genome sequencing data of parasites from eight different geographical locations, four from ML-susceptible populations and the other four from ML-loss of efficacy (LOE) populations, were used for polymorphism analysis. We identified 1762 single nucleotide polymorphic (SNP) sites (1508 intronic and 126 exonic) in these 224 ion channel genes/subunits with an overall polymorphic rate of 0.18%. Of the SNPs found in the exon regions, 129 of them caused a non-synonymous type of polymorphism. Fourteen of the exonic SNPs caused a change in predicted secondary structure. A few of the SNPs identified may have an effect on gene expression, function of the protein and resistance selection processes. PMID- 27682350 TI - GLUCOCORTICOID REPLACEMENT IN CHRONIC ADRENAL INSUFFICIENCY: EVALUATING THE EVIDENCE FOR OPTIMAL THERAPY. PMID- 27682351 TI - INCREASED RATES OF SMOKING CESSATION OBSERVED AMONG TRANSGENDER WOMEN RECEIVING HORMONE TREATMENT. AB - OBJECTIVE: According to the Centers for Disease Control, while 68% of adult smokers nationally desire to quit, only 6.2% successfully quit in a given year. Transgender women seen for hormone therapy at Boston Medical Center (BMC) are strongly advised to quit smoking before the start of treatment, not only due to general health benefits, but also because of the concern for increased thromboembolic events with estrogen therapy. Transgender men are given the same recommendation regarding tobacco as any patient. METHODS: We retrospectively examined 156 patients' charts, 120 transgender women and 36 transgender men, from the Transgender Center at BMC. Thirty-five charts were excluded, as they did not contain smoking data (29 transgender women and 6 transgender men). RESULTS: Twenty-eight transgender women (31%) were current smokers when they began treatment. Of those, 64% quit smoking over the course of initiating treatment. Of the 30 transgender men included in this study, 8 (27%) were current smokers when they began treatment. Of those, 25% quit smoking over the course of initiating treatment. CONCLUSION: Although others report that discussing tobacco use with a healthcare provider can increase rates of smoking cessation as seen with transgender men at our center, the substantially increased rate of smoking cessation among our transgender women suggests that greater impact can be achieved when a life-changing event is leveraged. Further, while some physicians raise concern over morbidity from hormone therapy, in our experience, good health habits initiated with care in our system more than outweigh the modest risks currently described. Abbreviation: BMC = Boston Medical Center. PMID- 27682352 TI - PRIMARY ALDOSTERONISM IN THE PRIMARY CARE CLINIC: RIFE OR RARE? PMID- 27682353 TI - CLINICAL OUTCOMES AND SELF-REPORTED SYMPTOMS IN PATIENTS WITH ACROMEGALY: AN 8 YEAR FOLLOW-UP OF A LANREOTIDE STUDY. AB - OBJECTIVE: The aim of this study was to evaluate the proportion of patients with acromegaly who remained on long-term lanreotide depot after completion of an open label multicenter phase III clinical trial (SALSA: A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel), compare baseline and long-term follow-up symptoms scores, and correlate scores with individual longitudinal clinical outcomes. METHODS: Records of all subjects previously enrolled at the Massachusetts General Hospital site of SALSA were reviewed. Those who remained on lanreotide were interviewed and asked to complete a questionnaire that they had filled out in SALSA in 2007 regarding their current symptomatology and injection side effects, as well as to complete the Acromegaly Quality of Life Questionnaire. Furthermore, clinical, biochemical, and radiographic data related to acromegaly and its comorbidities were tracked throughout follow-up. RESULTS: Six out of 7 patients chose to remain on lanreotide, and 5 of them continued lanreotide depot through last follow-up, for up to 8 years or in 1 case until death. In all cases, lanreotide remained well tolerated, and insulin-like growth factor-1 levels and pituitary imaging remained well controlled on stable doses. While comorbidities persisted or developed, the self-reported symptom score after up to 8 years of therapy showed a significant decrease in frequency or resolution in symptoms that were reported at baseline. CONCLUSION: This study shows a significant decrease in frequency or resolution in self-reported symptoms in well-controlled patients receiving long-term lanreotide therapy. ABBREVIATIONS: AcroQoL = Acromegaly Quality of Life Questionnaire GH = growth hormone GI = gastrointestinal IGF-1 = insulin-like growth factor-1 SALSA = A Multi Center Open Label Study to Assess the Ability of Subjects With Acromegaly or Their Partners to Administer Somatuline Autogel. PMID- 27682354 TI - FREE AND BIOAVAILABLE 25-HYDROXYVITAMIN D LEVELS IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM. AB - OBJECTIVE: To evaluate free and bioavailable 25-hydroxyvitamin D (25[OH]D) levels in primary hyperparathyroidism (PHPT) patients. METHODS: Fifty PHPT patients and 50 healthy age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. Levels of 25(OH)D were determined by a radioimmunoassay and vitamin D binding protein (DBP) were determined by an enzyme-linked immunosorbent assay. Free and bioavailable 25(OH)D were calculated utilizing equations that use average binding coefficients for DBP and albumin. RESULTS: There was no significant difference in age and BMI between PHPT patients and controls (P>.05). Levels of 25(OH)D, DBP, and DBP-bound 25(OH)D were lower in PHPT patients compared to controls (P<.01). There was no significant difference in free and bioavailable 25(OH)D levels between PHPT patients and controls (P>.05). Levels of intact parathyroid hormone were inversely correlated with free (r = -0.217; P<.05) and bioavailable 25(OH)D levels (r = -0.296; P<.01). CONCLUSION: Serum total 25(OH)D levels were lower, while free and bioavailable 25(OH)D remained similar in patients with PHPT compared to controls. We suggest that low 25(OH)D levels might not reflect true vitamin D nutrition status in PHPT patients. ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D BMI = body mass index DBP = vitamin D-binding protein iPTH = intact parathyroid hormone PHPT = primary hyperparathyroidism. PMID- 27682355 TI - SURGICAL OUTCOMES OF PROLACTINOMAS IN RECENT ERA: RESULTS OF A HETEROGENOUS GROUP. AB - OBJECTIVE: Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. METHODS: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. RESULTS: Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P<=.001) or atypical (P = .003) adenomas. CONCLUSION: Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field. PMID- 27682356 TI - EVALUATION OF OUTCOMES AND COMPLICATIONS IN PATIENTS WHO EXPERIENCE HYPOGLYCEMIA AFTER CARDIAC SURGERY. AB - OBJECTIVE: The objective of the study was to elucidate 30-day and long-term outcomes in patients experiencing postoperative hypoglycemia. METHODS: We conducted a retrospective review of patients who underwent cardiac surgery between September 4, 2007, and April 30, 2011, at Northwestern Memorial Hospital who had intensive treatment of hyperglycemia postoperatively. Of 1,325 patients, 215 experienced a hypoglycemic episode (blood glucose <70 mg/dL) within the first 3 postoperative days. A total of 198 were propensity-score (PS) matched to 363 patients without hypoglycemia. The analysis consisted of a comparison of 30-day cardiac outcomes and long-term mortality between those who experienced a hypoglycemic event and those who did not. RESULTS: Between patients who experienced hypoglycemia compared to those that did not, there were no significant differences in mean glucose values while on insulin drips (119.8 +/- 33.5 mg/dL vs. 120.9 +/- 30.5 mg/dL; P = .69) or subcutaneous insulin (122.0 +/- 38.0 mg/dL vs. 127.2 +/- 35.5 mg/dL; P = .11) or postoperative surgical complication rates (30-day mortality: 3.5% vs. 1.7%; complications (any): 40% vs. 42%; 30-day re-admissions: 13% vs. 13%; all cardiac complications: 35% vs. 31%; and all infections: 8% vs. 5%). Over an average of 5.1 +/- 2.2 years following index surgery, there was higher all-cause mortality among those PS-matched who had experienced hypoglycemia compared to those who had not (log-rank P = .031), primarily due to those (n = 32) experiencing more than one episode of hypoglycemia. CONCLUSION: Postoperative hypoglycemia did not negatively impact immediate surgical complication rates but was associated with a significant risk of increased postoperative morbidity and long-term all-cause mortality in patients experiencing multiple episodes of hypoglycemia. ABBREVIATIONS: BG = blood glucose BMI = body mass index CARD = Cardiovascular Research Database HR = hazard rate PS = propensity score. PMID- 27682357 TI - Racecadotril May Reduce Diarrhoea in Microvillous Inclusion Disease. PMID- 27682358 TI - UPPS-P model impulsivity and marijuana use behaviors in adolescents: A meta analysis. AB - BACKGROUND: Impulsivity is often included as a risk factor in models of adolescent marijuana use behaviors; however, the magnitude of the association between impulsivity and marijuana use behaviors is variable across studies. The present study reviewed existent literature to 1) quantify the relationship between separable impulsivity-related traits and both marijuana use and negative marijuana consequences and 2) quantify the size of the effect of gender on these relationships. METHOD: Thirty-eight studies (41 independent samples) were meta analyzed using a random effects model to examine the relationship between impulsivity traits and marijuana use behaviors. RESULTS: Marijuana use was significantly related to all impulsivity-related traits except lack of perseverance (r's ranging from 0.13-0.23, p's<0.01). Negative marijuana consequences were only significantly related to sensation seeking, lack of planning, and positive urgency (r's ranging from 0.37-0.39, p's<0.01). Effects were small for marijuana use, but medium for negative marijuana consequences. Gender was not a significant moderator of any relationships. CONCLUSIONS: Impulsivity-related traits had more robust relationships with negative marijuana consequences than marijuana use, suggesting impulsivity-related traits are important in differentiating adolescents most likely to experience negative consequences from marijuana use. Few relationships examined gender and many of the impulsivity-related traits, other than sensation seeking. Data and trends suggest a more multi-dimensional approach to marijuana use and consequences is warranted. PMID- 27682359 TI - A review of computer-aided oral and maxillofacial surgery: planning, simulation and navigation. AB - INTRODUCTION: Currently, oral and maxillofacial surgery (OMFS) still poses a significant challenge for surgeons due to the anatomic complexity and limited field of view of the oral cavity. With the great development of computer technologies, he computer-aided surgery has been widely used for minimizing the risks and improving the precision of surgery. Areas covered: The major goal of this paper is to provide a comprehensive reference source of current and future development of computer-aided OMFS including surgical planning, simulation and navigation for relevant researchers. Expert commentary: Compared with the traditional OMFS, computer-aided OMFS overcomes the disadvantage that the treatment on the region of anatomically complex maxillofacial depends almost exclusively on the experience of the surgeon. PMID- 27682360 TI - Identification of cryptic Candida species by MALDI-TOF mass spectrometry, not all MALDI-TOF systems are the same: focus on the C. parapsilosis species complex. AB - Data about the performance of MALDI-TOF mass spectrometry against cryptic Candida species are limited. According to our findings within the C. parapsilosis species complex, microbiologists should be aware that the choice of the instrument is critical for accurate species identification due to the risk of misidentification in the clinical setting. PMID- 27682361 TI - Hypochlorite converts cysteinyl-dopamine into a cytotoxic product: A possible factor in Parkinson's Disease. AB - The dopamine oxidation product cysteinyl-dopamine has attracted attention as a contributor to the death of dopaminergic neurons in Parkinson's disease. Treatment of cysteinyl-dopamine with hypochlorite yields an even more cytotoxic product. This product has potent redox-cycling activity and initiates production of superoxide in PC12 cells. Taurine, which scavenges hypochlorite, protects PC12 cells from cysteinyl-dopamine but not from the hypochlorite product, suggesting that the product, not cysteinyl-dopamine itself, is toxic. Furthermore, rotenone, which enhances expression of the hypochlorite-producing enzyme myeloperoxidase, increases the cytotoxicity of cysteinyl-dopamine but not of the hypochlorite product. This suggests that dopamine oxidation to cysteinyl-dopamine followed by hypochlorite-dependent conversion to a cytotoxic redox-cycling product leads to the generation of reactive oxygen species and oxidative stress and may contribute to the death of dopaminergic neurons. PMID- 27682362 TI - 4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling. AB - We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including 4 Hydroxynonenal (4-HNE). 4-HNE is notorious for producing protein post-translation modification (PTM) via reactions with the amino acids: cysteine, histidine and lysine. Thus, we sought to determine if 4-HNE mediated post-translational modification of TRPV1 could account for dysfunctional TRPV1-mediated signaling observed in diabetes. Our initial studies demonstrate 4-HNE infusion decreases TRPV1-dependent coronary blood flow in C57BKS/J (WT) mice. Further, we found that TRPV1-dependent vasorelaxation was suppressed after 4-HNE treatment in isolated mouse coronary arterioles. Moreover, we demonstrate 4-HNE significantly inhibited TRPV1 currents and Ca2+ entry utilizing patch-clamp electrophysiology and calcium imaging respectively. Using molecular modeling, we identified potential pore cysteines residues that, when mutated, could restore TRPV1 function in the presence of 4-HNE. Specifically, complete rescue of capsaicin-mediated activation of TRPV1 was obtained following mutation of pore Cysteine 621. Finally, His tag pull-down of TRPV1 in HEK cells treated with 4-HNE demonstrated a significant increase in 4-HNE binding to TRPV1, which was reduced in the TRPV1 C621G mutant. Taken together these data suggest that 4-HNE decreases TRPV1-mediated responses, at both the in vivo and in vitro levels and this dysfunction can be rescued via mutation of the pore Cysteine 621. Our results show the first evidence of an amino acid specific modification of TRPV1 by 4-HNE suggesting this 4-HNE dependent modification of TRPV1 may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes. PMID- 27682364 TI - Renal transplant immunology in the last 20 years: A revolution towards graft and patient survival improvement. AB - To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969 * Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T. The mystique of organ transplantation. J Am Coll Surg 2005 Aug;201(2):160-170]. In fact, the first successful identical-twin kidney transplantation performed by Murray's team in December 1954 (Murray J et al. Renal homotransplantations in identical twins. Surg Forum 1955;6:432-436) was the example of an upside down translation medicine: Human clinical transplantation began and researchers tried to understand the underlying immune response and how to control the powerful rejection pathways through experimental models. In the last 20 years, we have witnessed an amazing progress in the knowledge of immunological mechanisms regarding alloimmune response and an outstanding evolution on the identification and characterization of major and minor histocompatibility antigens. This review presents an historical and clinical perspective of those important advances in kidney transplantation immunology in the last 20 years, which contributed to the improvement in patients' quality of life and the survival of end-stage renal patients. In spite of these significant progresses, some areas still need substantial progress, such as the definition of non-invasive biomarkers for acute rejection; the continuous reduction of immunosuppression; the extension of graft survival, and finally the achievement of real graft tolerance extended to HLA mismatch donor: recipient pairs. PMID- 27682365 TI - Low Gestational Weight Gain and Risk of Adverse Perinatal Outcomes in Obese and Severely Obese Women. AB - BACKGROUND: Our objective was to estimate associations between gestational weight gain z scores and preterm birth, neonatal intensive care unit admission, large- and small-for-gestational age birth, and cesarean delivery among grades 1, 2, and 3 obese women. METHODS: We included singleton infants born in Pennsylvania (2003 2011) to grade 1 (body mass index 30-34.9 kg/m, n = 148,335), grade 2 (35-39.9 kg/m, n = 72,032), or grade 3 (>=40 kg/m, n = 47,494) obese mothers. Total pregnancy weight gain (kg) was converted to gestational age-standardized z scores. Multivariable Poisson regression models stratified by obesity grade were used to estimate associations between z scores and outcomes. A probabilistic bias analysis, informed by an internal validation study, evaluated the impact of body mass index and weight gain misclassification. RESULTS: Risks of adverse outcomes did not substantially vary within the range of z scores equivalent to 40-week weight gains of -4.3 to 9 kg for grade 1 obese, -8.2 to 5.6 kg for grade 2 obese, and -12 to -2.3 kg for grade 3 obese women. As gestational weight gain increased beyond these z score ranges, there were slight declines in risk of small-for gestational age birth but rapid rises in cesarean delivery and large-for gestational age birth. Risks of preterm birth and neonatal intensive care unit admission were weakly associated with weight gain. The bias analysis supported the validity of the conventional analysis. CONCLUSIONS: Gestational weight gain below national recommendations for obese mothers (5-9 kg) may not be adversely associated with fetal growth, gestational age at delivery, or mode of delivery. PMID- 27682368 TI - Barriers to nursing home staff accessing CPD must be broken down. AB - A study on priorities for the professional development of registered nurses (RNs) in nursing homes published in Age and Ageing ( page 6 ) has identified that staff shortages, lack of access to NHS courses and lack of paid study time are the main reasons why RNs do not access continuing professional development (CPD) activities. Specialist gerontological education for care home nurses was, however, seen as a means to ensure that care home nursing attracts the best people. PMID- 27682363 TI - Polyamine- and NADPH-dependent generation of ROS during Helicobacter pylori infection: A blessing in disguise. AB - Helicobacter pylori is a Gram-negative bacterium that specifically colonizes the gastric ecological niche. During the infectious process, which results in diseases ranging from chronic gastritis to gastric cancer, the host response is characterized by the activation of the innate immunity of gastric epithelial cells and macrophages. These cells thus produce effector molecules such as reactive oxygen species (ROS) to counteract the infection. The generation of ROS in response to H. pylori involves two canonical pathways: 1) the NADPH-dependent reduction of molecular oxygen to generate O2*-, which can dismute to generate ROS; and 2) the back-conversion of the polyamine spermine into spermidine through the enzyme spermine oxidase, leading to H2O2 production. Although these products have the potential to affect the survival of bacteria, H. pylori has acquired numerous strategies to counteract their deleterious effects. Nonetheless, ROS mediated oxidative DNA damage and mutations may participate in the adaptation of H. pylori to its ecological niche. Lastly, ROS have been shown to play a major role in the development of the inflammation and carcinogenesis. It is the purpose of this review to summarize the literature about the production of ROS during H. pylori infection and their role in this infectious gastric disease. PMID- 27682366 TI - How Many Is Too Many? On the Relationship between Research Productivity and Impact. AB - Over the last few decades, the institutionalisation of quantitative research evaluations has created incentives for scholars to publish as many papers as possible. This paper assesses the effects of such incentives on individual researchers' scientific impact, by analysing the relationship between their number of articles and their proportion of highly cited papers. In other words, does the share of an author's top 1% most cited papers increase, remain stable, or decrease as his/her total number of papers increase? Using a large dataset of disambiguated researchers (N = 28,078,476) over the 1980-2013 period, this paper shows that, on average, the higher the number of papers a researcher publishes, the higher the proportion of these papers are amongst the most cited. This relationship is stronger for older cohorts of researchers, while decreasing returns to scale are observed for recent cohorts. On the whole, these results suggest that for established researchers, the strategy of publishing as many papers as possible did not yield lower shares of highly cited publications, but such a pattern is not always observed for younger scholars. PMID- 27682367 TI - Association Between Inferior Vena Cava Filter Insertion in Trauma Patients and In Hospital and Overall Mortality. AB - Importance: Trauma patients admitted to the hospital are at increased risk of bleeding and thrombosis. The use of inferior vena cava (IVC) filters in this population has been increasing, despite a lack of high-quality evidence to demonstrate their efficacy. Objective: To determine if IVC filter insertion in trauma patients affects overall mortality. Design, Setting, and Participants: This retrospective cohort study used stratified 3:1 propensity matching to select a control population similar to patients who underwent IVC filter insertion at Boston Medical Center (a level I trauma center at Boston University School of Medicine) between August 1, 2003, and December 31, 2012. Among patients with an IVC filter and matched controls, age, sex, race/ethnicity, and Injury Severity Score were entered into a multivariable logistic regression model to calculate a propensity score. Matching was stratified by the date of injury. Main Outcomes and Measures: Multivariable logistic regression was used to compare hospital mortality across both groups, adjusting for age, sex, race/ethnicity, Injury Severity Score, and brain injury severity using the head and neck Abbreviated Injury Score. To determine any significant difference in mortality, patient characteristics and mortality data from the National Death Index were analyzed in all patients and in those who survived 24, 48, and 72 hours after injury, as well as at hospital discharge. Results: Among 451 trauma patients with an IVC filter and 1343 matched controls without an IVC filter, the mean (SD) age was 47.4 (21.5) years. The median Injury Severity Score overall was 24 (range, 1-75). Based on a mean follow-up of 3.8 years (range, 0-9.4 years), there was no significant difference in overall mortality or cause of mortality in patients with vs without an IVC filter who survived more than 24 hours from the time of injury, independent of the presence or absence of deep vein thrombosis or pulmonary embolism at the time of IVC filter placement. Additional analyses at shorter intervals of 6 months and 1 year after discharge also showed no significant difference between the 2 groups of patients. Eight percent (38 of 451) of the IVC filters were removed at Boston Medical Center during the follow up period. Conclusions and Relevance: The research herein demonstrates no significant difference in survival in trauma patients with vs without placement of an IVC filter, whether in the presence or absence of venous thrombosis. The use of IVC filters in this population should be reexamined because filter removal rates are low and there is increased risk of morbidity in patients with filters that remain in place. PMID- 27682370 TI - Coalition to keep EU workers in UK. AB - A coalition of 29 health and social care organisations has been created to ensure there are enough nurses and other workers in place when the UK withdraws from the European Union (EU). PMID- 27682369 TI - Residential staff need more training in personal care. AB - Care home nurses need more access to training in personal care and dementia because they are being poorly prepared by undergraduate courses, a study has concluded. PMID- 27682372 TI - Funding cuts are leaving older and disabled people 'outside the system'. AB - Older people are bearing the brunt of cuts to social care and increasing numbers of care homes could go out of business, a new report warns. PMID- 27682371 TI - Story in numbers. AB - Parkinson's UK's 2015 audit on Parkinson's services. PMID- 27682373 TI - Care programme recruits nurses. AB - Senior nurses and allied health professionals (AHPs) in England are being encouraged to apply for places on a 1-year programme to improve care for older people. PMID- 27682374 TI - Picture of a 'broken' workforce. AB - The decline in district nurse numbers is well known. A 48% drop between 2000 and 2014 has seen numbers fall to fewer than 6,000 full-time roles in England. PMID- 27682377 TI - Delayed discharge. AB - Essential facts Delays in discharging older people from hospital cost the NHS L820 million a year, according to a report from the National Audit Office (NAO). PMID- 27682378 TI - Prevention is best strategy for Alzheimer's disease. AB - Most people with Alzheimer's disease have late onset disease in which genetic predisposition and environmental factors combine to contribute to its development. PMID- 27682380 TI - Depression is often undiagnosed in older people with cancer. AB - Depression is commonly associated with cancer, either as a pre-existing condition or as a consequence of the illness. Depression is also associated with adverse outcomes such as poor treatment compliance, short survival, long hospital stays, early functional decline, impaired quality of life and increased healthcare costs. PMID- 27682379 TI - How older people store and use food could increase listeriosis risk. AB - People with weakened immunity, including older adults, are known to be at increased risk of foodborne disease, in particular, listeriosis. Listeriosis is associated with the highest levels of hospitalisation and mortality of all foodborne pathogens in the UK. PMID- 27682381 TI - How care homes are becoming learning hubs. AB - For too long the care sector has received a disproportionate amount of negativity from the media and health professionals. PMID- 27682382 TI - More people behind bars nearing end of life. AB - As prisons and probation ombudsman, I investigate deaths in prison in England and Wales. Demand for my services has never been greater, with a record 304 deaths to investigate in 2015-16, 42% more than 5 years before. PMID- 27682385 TI - Oral health. AB - If the oral health problems of older people are left undetected or untreated, physical, psychological and social health can deteriorate ( Public Health England (PHE) 2015 ). PMID- 27682386 TI - Development of an activities care crew to support patients. AB - Improving care for people with dementia in acute hospitals is a priority in the UK. The Royal Berkshire Hospital in Reading has implemented a range of initiatives, including environmental changes to older people's care wards, development of workforce skills and knowledge, engagement with third sector providers, use of volunteers, and the development of an activities care crew. This article focuses on the work of the activities care crew. The care crew formation, using monies from vacant posts, has supported the provision of one-to one nursing and engagement of patients in meaningful activities. Overall, the initiatives have reduced the number of falls with serious harm, improved the experience of people with dementia and their families, and supported partnership working with patients, families and multidisciplinary teams. PMID- 27682387 TI - Developing a culture of relationship-centred care in a care home group. AB - This article outlines the development of a new way of working across a group of care homes in south east Wales, based on a philosophy of relationship-centred care and an ethos of empowerment for older people in the homes. The underpinning aim was to enable residents to have a good quality of life, reflecting recommendations made by the Older People's Commissioner for Wales in a 2014 review into the quality of life and care of older people living in care homes in the country. After the introduction of the new way of working, the care home group were approached by a university to take part in a collaborative project offering nursing students clinical placements in the care homes, mentored by registered nurses employed there. The collaboration between the university and the care homes meant that nursing students became enveloped in the person-centred culture, receiving positive exposure to nursing older people early in their careers. It is hoped that the clinical placements may encourage them to consider careers in the specialty. PMID- 27682388 TI - Culture change in care homes: development and facilitation. AB - This article is the second of a two-part series that explores a programme of culture change in care homes. In this article, the authors describe their independent development and facilitation of a flexible learning programme for care homes, designed to meet a quality improvement request made by a care home company. The two selected care homes' staff conducted a review of their care culture, as a precursor to their creation of a new care philosophy. These activities provided a firm foundation from which the homes could, in theory, become a Remedial Enterprise Active Learning care home. Although the learning programme was not completed due to unavoidable circumstances, the staff's experiences highlight some of the challenges and successes that may be experienced when seeking to improve care homes' learning culture and practice. PMID- 27682389 TI - A voice for older patients. AB - How did you become an older people's nurse? I have never seen it as a specialty, but as part of my job as a nurse. I work in the Bournemouth area, as nurse consultant intermediate care at Dorset HealthCare University NHS Foundation Trust, where we have a large older population. PMID- 27682390 TI - Bowel cancer screening. AB - Bowel cancer is the fourth most common cancer in England and the second highest cause of cancer deaths. PMID- 27682391 TI - Self-care among children. AB - Based on two systematic reviews and research into different self-care support programmes in the UK, this article in Nursing Children and Young People examines the evidence for self-care among children and young people with physical and mental health conditions. PMID- 27682392 TI - Guidelines for safe consumption of caffeine. AB - 'Guidelines for safe consumption of caffeine indicate that an intake of up to 400mg daily is safe for adults. Average tea consumption in the UK, at 2 to 3 servings daily, fits within this. Given the potential benefits of tea for health, consumption could rise to 8 servings daily and still be within safe limits'. PMID- 27682393 TI - Leadership styles. AB - Promoting the public health agenda has become a multidisciplinary enterprise, and strong partnerships between allied healthcare professionals and their social care counterparts are essential for successful outcomes. PMID- 27682394 TI - The Teaching Care Homes pilot programme. AB - 'The Teaching Care Homes pilot programme aims to create care centres that demonstrate excellence and innovation in nurse-led care, and learning environments that benefit staff and students'. PMID- 27682395 TI - Pneumocandin B0-imprinted Polymer Using Surface-imprinting Technique for Efficient Purification of Crude Product. AB - In this work, we prepared surface molecularly imprinted polymer (MIP) for selective recognition of pneumocandin B0 (PNB0). Methacrylic acid (MAA) was first grafted onto silica gel particles (SiO2) in the manner of "grafting from" by using 3-methacryloxypropyl trimethoxysilane as intermedium, and then PNB0 molecules were imprinted on the surface of the obtained particles in the presence of ethylene glycol diglycidyl ether as the cross-linker. The prepared MIP PMAA/SiO2 was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and thermo-gravimetric analysis, which confirmed the successful grafting of MAA onto SiO2 and the grafting degree was calculated to be 12.50 wt%. The binding properties of the products were investigated and it is found that the binding process of PNB0 followed the pseudo-second-order kinetic model. The as-prepared material also displays relatively quick adsorption kinetics and decent recognition affinity toward the template over its structurally related compound. PMID- 27682396 TI - Simultaneous Determinations of Eleven Bioactive Components in Suanzaoren Decoction Granules by High-Performance Liquid Chromatography and Its Application to the Quality Control in Productive Processes. AB - A simple and reliable method using high-performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA) was firstly established for the determinations of eleven bioactive compounds (neomangiferin, mangiferin, spinosin, liquiritin apioside, liquiritin, fumalic acid, 6'''-feruloylspinosin, senkyunolide I, isoliquiritin, glycyrrhizic acid and senkyunolide A) in Suanzaoren decoction (SZRD) extract and its granules. The chromatographic analysis was performed on a C18 column at 30 degrees C. Excellent linear behaviors over the investigated concentration ranges were observed with the values of R(2) being higher than 0.9990 for all analytes. The developed method showed good precision and accuracy with overall intra- and inter-day variations of less than 2.0%, and overall recoveries in the range of 97.2 - 102.1%. The validated method was successfully applied to the determination of eleven components in SZRD samples from different production batches, including SZRD extract, lab-made SZRD granules and clinical medicine. This accurate and reliable HPLC-PDA method will be helpful for improving the quality evaluation of SZRD granules and its quality control in productive processes. PMID- 27682397 TI - Selective Concentration of Ultra-trace Acetone in the Air by Cryogenic Temperature Programmed Desorption (cryo-TPD). AB - A gas analytical technique with compact size, low cost, sufficient sensitivity, and excellent reproducibility is required in many fields including exhaled breath analysis for medical monitoring. In the present study, we examined selective acetone concentration by quench condensation at cryogenic temperature followed by temperature programmed desorption (cryogenic temperature programmed desorption (cryo-TPD)) for possible applications to breath analysis for medical monitoring. The essence of cryo-TPD is rough mass selection by thermal desorption followed by quantification of certain species using mass spectrometry. The performance of cryo-TPD was investigated in the acetone concentration range below 1 * 10(-6) volume fraction (1 ppmv). It was found that acetone is selectively quench condensed on a tungsten substrate at 50 K without the major components of air, such as N2 and O2. The concentrated acetone gas was obtained by the following thermal desorption at around 151 K. Under conditions of condensation for 1 min and pressure of 1 * 10(-2) Pa, the lowest limit of detection reached well below 10 * 10(-9) volume fraction (10 ppbv). The relationship between the cetone intensity of cryo-TPD and the acetone concentration in the gas was almost linear in the ppbv range. The separation of acetone and propanal using the fragmentation pattern, which have almost the identical molecular mass, was also demonstrated in the present study. PMID- 27682398 TI - Combination of Microporous Hollow Carbon Spheres and Nafion for the Individual Metal-free Stripping Detection of Pb(2+) and Cd(2.). AB - Here, the combination of Nafion with microporous hollow carbon spheres (MHCS) is first proposed to fabricate a disposable metal-free electrode for heavy metal stripping sensing. The MHCS-Nafion composite film electrode is prepared by drop casting a mixture of MHCS and Nafion onto the lab-made screen-printed carbon electrode (SPCE(*)). Results demonstrate that the interfusion of MHCS into Nafion offers enhanced performance for the electro-enrichment and stripping of lead and cadmium over the only Nafion film: 1) abundant MHCS immobilized on the electrode surface serve as effective nucleation sites for metal ion reduction; 2) the mixing of MHCS into Nafion enlarges the active surface of negative-charged Nafion for the electrostatic adsorption of metal cations. The proposed MHCS Nafion/SPCE(*) provides linear responses for Pb(2+) and Cd(2+) in the range of 2 200 MUg/L, with a detection limit of 1.37 and 1.63 MUg/L, respectively. Practical applications of the sensor in water sample detection with good accuracy have also been confirmed. PMID- 27682399 TI - Fluorescence Resonance Energy Transfer-based Biosensor Composed of Nitrogen-doped Carbon Dots and Gold Nanoparticles for the Highly Sensitive Detection of Organophosphorus Pesticides. AB - The present article reports a novel biosensor for organophosphorus pesticides based on fluorescence resonance energy transfer (FRET) between nitrogen-doped carbon dots (NC-dots) and gold nanoparticles (AuNPs). The effective NC-dots/AuNPs assembly through the Au-N interaction results in good fluorescence quenching. Active acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylthiocholine into -SH containing thiocholine to replace the NC-dots and trigger the aggregation of AuNPs. In the presence of paraoxon, the activity of AChE is inhibited, and thus preventing the generation of thiocholine, causing fewer NC dots to be replaced. As a consequence, the fluorescence intensity gradually decreases with increasing amount of paraoxon. This biosensor does not require any complex synthesis or modification, and the results show a wide detection range of from 10(-4) to 10(-9) g/L with a detection limit of 1.0 * 10(-9) g/L (3.6 * 10( 12) mol/L). Two linear response regions have been reported with a turning point at about 10(-6) g/L and three different factors that would influence the response behavior. These phenomena discussed in detail so as to explain the special response mechanism. PMID- 27682400 TI - Arsenic Speciation and Cadmium Determination in Tobacco Leaves, Ash and Smoke. AB - The concentrations of arsenic (As) and cadmium (Cd) in the tobacco leaves, ash and smoke of 10 kinds of cigarettes collected from different countries worldwide were determined by ICP-MS after microwave-assisted digestion. Total As and Cd concentrations in the tobacco leaves ranged from 0.20 to 0.63 and 1.8 to 9.9 mg kg(-1), respectively. By the speciation analysis of As in tobacco leaves and ash by HPLC-ICP-MS following acid extraction, arsenite [As(III)] and arsenate [As(V)] were determined and trace amounts of monomethylarsonic acid (MMAA), dimethylarsinic acid (DMAA), trimethylarsine oxide (TMAO), tetramethylarsonium (TeMA) and some unidentified As species were also found. Arsenic speciation for smoke absorbed in an aqueous solution was carried out. The sum of the As species in tobacco leaves, ash and smoke was in good agreement with the result of total As determination in each sample, and the recoveries of speciation were 100 +/- 10%. The distributions and the behaviors of As species were clarified. PMID- 27682401 TI - Glucosylation Mediated Rolling Circle Amplification Combined with a qPCR Assay for the Detection of 5-Hydroxymethylcytosine. AB - The detection of 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic mark, is essential to its functional study. Here, an efficient and simple two step-amplification method to detect 5hmC mediated by glucosylation is reported, which combines rolling circle amplification (RCA) and a quantitative polymerase chain reaction (qPCR). In the first step RCA, the glucosylated 5hmC (5ghmC), but not 5hmC, 5-methylcytosine (5mC) or cytosine (C) bases, could directly and specifically inhibit the activity of phi29 DNA polymerase, resulting in less RCA product compared to that using C-/5mC-/5hmC-containing templates. Then, the second step qPCR is adopted to test and verify the difference of the product quantity of 5ghmC-related RCA. The results show that the delta cycle threshold, DeltaCt, obtained by subtracting the cycle threshold value (Ct) of C-related qPCR from that of each qPCR, of 5ghmC-related qPCR reaches 1.59 +/- 0.03, significantly different from that of C-/5mC-/5hmC-related qPCR (-0.00 +/- 0.09, 0.06 +/- 0.08 and -0.02 +/- 0.03, respectively). Meanwhile, a linear relationship is observed between the 5ghmC levels and the DeltaCt values. This suggests that the strategy has a potential application for 5hmC detection and quantification. PMID- 27682402 TI - Chromatographic Fingerprint-Bioactivity Relationships of the Antitumor Properties of Bufo bufo gargarizans Skin Extracts. AB - Statistical analyses of high-performance liquid chromatography (HPLC)-based chemical fingerprints of Bufo bufo gargarizans toad skin extracts were integrated with antitumor evaluations as a means to more effectively identify bioactive constituents. Specifically, chemical fingerprints of Bufo bufo gargarizans skin extract samples obtained from ten different regions in China were generated by HPLC, and then subjected to similarity analysis and principal component analysis (PCA). Concurrently, a MCF-7 breast cancer cell model was adopted to obtain the antitumor activity of different toad skin extracts. The chromatographic fingerprint-bioactivity relationships of the Bufo bufo gargarizans extracts were then evaluated by Pearson correlation analysis. The results demonstrated that all skin extract samples inhibited the proliferation of MCF-7 cells to some extent, and that there was a correlation between the chemical fingerprints and the anti proliferative activity. Bufotalin, bufalin, and cinobufagin, three known components of Bufo bufo gargarizans that were identified in the chemical fingerprints, were highlighted as constituents responsible for the observed bioactivity. The activity of cinobufagin was confirmed by cell viability and colony formation assays using MCF-7 cells. The approach documented here provides a more effective means to associate chemical information on medicinal extracts with the principle components responsible for their bioactivity, and to therefore expedite drug discovery. PMID- 27682403 TI - Preparation of Pb(II) Ion Imprinted Polymer and Its Application as the Interface of an Electrochemical Sensor for Trace Lead Determination. AB - An ion imprinted polymer (IIP) was synthesized by using Pb(II) as a template, methacrylic acid as a monomer, 8-hydoxyquinoline as a ligand, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, and azobisisobutyronitrile as initiator. It can be applied to prepare lead ion selective voltammetric sensor for Pb(II) adsorption and trace detection. The Pb(II)-IIP was characterized by FTIR spectra and SEM image. Under optimized conditions of polymerization, the Pb(II)-IIP showed good adsorption behavior toward Pb(II), with a magnitude of three times higher than that of the non imprinted polymer (NIP). Also, it exhibited a favorable selectivity for Pb(II), compared with other heavy metal ions of Hg(II), Cd(II), Cu(II), and a negligible adsorption to the other cations. The synthesized IIP was used to determine trace levels of Pb(II) in food and water samples, with a calibration linear range over Pb(II) concentrations of 0.05 - 60 MUM and a limit of detection at 0.01 MUM. PMID- 27682405 TI - Facile Synthesis of a Luminescent Material, PAN@{SiO2}n, Having a Simultaneous Binding Capacity of High and Low Oxidation States: HOMO and LUMO, Quantum mechanical Descriptor of Break-through Capacity. AB - A time-cost effective, chemically stable mesoporous resin (FSG-PAN), simultaneous binder of two different metal centers (both high (Cd(II)) and low (Tl(I)) oxidation states), has been synthesized by immobilizing azo-dye (1-(2-pyridylazo) 2-napthol: PAN) on functionalized silica gel (FSG). Its corresponding synthesized nano material possesses good luminescent properties, and has been utilized in fluoride sensing at trace levels (1.8 * 10(-6) - 7.2 * 10(-6) M). The composition ({Si[OSi]p=4[H2O]x=0.81}12[-Si(CH3)2-NH-C6H4-N=N-PAN]4..51H2O) and structure (tetrahedral) have been well assessed. Under the optimum extraction conditions, the soft extractor (etaFSG-PAN = 1.31 eV), FSG-PAN quantitatively extracts the soft metal centers Cd(II), followed by Tl(I) at its respective HOMO and LUMO by soft-soft interactions. The extractor possesses a high Brunauer-Emmett-Teller (BET) surface area (SABET) (374 m(2) g(-1)), high preconcentration factor (PF, 192), selective pore size and two kinds of break-through capacity (BTCHOMO, 945 MUmol g(-1); BTCLUMO, 120 MUmol g(-1)). BTC is spelled out as a function of the electron density over the ligand binding site as analyzed from a DFT calculation. PMID- 27682404 TI - Simultaneous Determination of Seven Neuroactive Steroids Associated with Depression in Rat Plasma and Brain by High Performance Liquid Chromatography Tandem Mass Spectrometry. AB - Sensitive and specific biomarkers are required for the diagnosis and treatment of depression because the existing diagnostic criteria are subjective and could produce false positives or negatives. Some endogenous neuroactive steroids that have shown either antidepressant effects or concentration changes in individuals with depression could provide potential biomarkers. In this study, a simple and specific method was developed to simultaneously determine seven endogenous neuroactive steroids in biological samples: cortisone, cortisol, dehydroepiandrosterone, estradiol, progesterone, pregnenolone, and testosterone. After liquid-liquid extraction, chromatographic separation was achieved on a C18 column with gradient elution using water-methanol at a flow rate of 300 MUL min( 1). Detection and quantitation were performed by tandem mass spectrometry with atmospheric pressure chemical ionization and selected reaction monitoring. Plasma and brain neuroactive steroid levels were then determined in control rats and rats exposed to forced swimming, a classical rodent model of depression. The results showed that the plasma concentrations of testosterone, pregnenolone, and progesterone significantly increased in rats exposed to the forced swimming test. In contrast, brain homogenate levels of cortisol, estradiol, and progesterone decreased, while pregnenolone levels were elevated in this model of depression. In conclusion, a new method to quantify neuroactive steroids was successfully developed and applied to their investigation in rat plasma and brain. The findings of this study indicated that plasma testosterone, pregnenolone, and progesterone levels could provide potential biomarkers for the diagnosis and treatment of depression. PMID- 27682406 TI - Fluorometric Determination of Epinephrine: A Green Approach. AB - Herein, a simple, sensitive and selective turn-on fluorescent method for the determination of epinephrine (EP), an important hormone and neurotransmitter, is described. The method is based on the interaction of EP with PEG6000 coated carbon nanoparticles (PCN) resulting in the fluorescence enhancement of PCN. A linear relationship was obtained between the fluorescence intensity and concentration of EP in the 9.90 * 10(-9) - 1.07 * 10(-7) M range; the detection limit being 7.59 * 10(-10) M. Furthermore, we demonstrated the application of the present approach in a synthetic urine sample, which suggested its great potential for diagnostic purposes. PMID- 27682407 TI - Effect of Long-time Heating for Polyvinyl Chloride and Polypropylene Resin Pellet Certified Reference Materials for Heavy Metal Analysis. AB - The effect of long-time heating for both polyvinyl chloride (PVC) and polypropylene (PP) resin pellet certified reference materials (CRMs) for heavy metal analysis, which contained Cd, Cr, Hg and Pb, was examined in the present study. The temperature of the drying oven was 80 degrees C, which was used for drying these CRMs before analysis, and the long-time heating was carried out for up to 480 h. As a result, a relative decrease in mass of ca. 0.3% was observed for both CRMs. Moreover, a decrease in concentration of ca. 10% was observed for Cr, even though the concentrations for other elements did not change during the long-time heating. Since the chemical form of Cr was an organometallic compound with lower melting point, it was considered that concentration decreased due to the heat. PMID- 27682408 TI - Direct Determination of Lead in Foods by Solid Sampling Electrothermal Vaporization Atomic Fluorescence Spectrometry. AB - A solid sampling method for the determination of lead in foods (including grains, vegetables and seafoods) using electrothermal vaporization atomic fluorescence spectrometry was established. The method introduced samples using electrothermal vaporization by quartz furnace and used on-line ashing and vaporization to remove matrix interferences for the specific trap of lead. It was proven by the certified reference material (CRM) and the recovery rate of the standards that the electrothermal vaporization was stable and there was no effect for sampling difference. The best operating program and parameters for the new method included ashing (850 degrees C, 160 s), vaporization and trap (1050 degrees C, 80 s; 800 degrees C, 10 s), release (800 degrees C, 10 s), and mixed Ar + H2 (85:15%, v/v) as carrier gas with flow rate of 500 mL/min. The relative standard deviations of repeated Pb measurements in CRMs were all below 5.0%, and the recovery rate ranged from 90.0 - 110.0%. The limit of detection (LOD) for the new method was 3.0 pg and the limit of quantification (LOQ) was 10.0 pg. The total time of analysis was less than 6 min. No significant differences existed between the results measured by the new method and microwave ICP-MS. PMID- 27682409 TI - Determination of Eicosapentaenoic, Docosahexaenoic, and Arachidonic Acids in Human Plasma by High-Performance Liquid Chromatography with Electrochemical Detection. AB - A high-performance liquid chromatography with electrochemical detection (HPLC ECD) system was developed for the simultaneous determination of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) in human plasma. In the present HPLC-ECD system, EPA, DHA, and AA were separated using a reverse-phase C30 column and detected based on the voltammetric reduction of 3,5 di-tert-butyl-1,2-benzoquinone (DBBQ). Chromatographic peak areas were proportional to the concentration of EPA, DHA, and AA from 0.75 MUM to 0.1 mM (r > 0.998). The concentrations of EPA, DHA, and AA in plasma from healthy human subjects after overnight fasting were determined, and the ratio of EPA to AA was obtained by the present HPLC-ECD method, which required 40 MUL of human plasma and a simple procedure of sample preparation using diethyl ether extraction. Moreover, changes in EPA, DHA, and AA concentrations in a human subject were monitored before and after fish oil supplement administration by the present HPLC ECD system. PMID- 27682410 TI - Evaluating the Translational Temperature of Molecules Laser-desorbed after Online Concentration Using Multiphoton Ionization Time-of-Flight Mass Spectrometry. AB - We describe a new technique for evaluating the translational temperature of molecules by applying online concentration via analyte adsorption/laser desorption, which is a sample-introduction technique for resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (REMPI-TOFMS). In the present study, analyte molecules were adsorbed via a narrowed capillary tip once, and then the flow of the carrier gas containing the analyte was stopped. After laser desorption, the ion signals induced by REMPI were monitored. Finally, the translational temperature could be calculated from the velocity distribution of the desorbed molecules by applying a Maxwell distribution. PMID- 27682411 TI - Extraction and Analysis of Disperse Dyes from Colored Polyester Single Fibers Using Liquid Chromatography/Linear Ion Trap Tandem Mass Spectrometry. AB - Nine disperse dyes extracted from colored polyester threads and single fibers of manufactory-supplied textiles by using centrifugal filtration were analyzed using liquid chromatography/linear ion trap tandem mass spectrometry (LC/LIT-MS(n)). Based on diode array detector data, dimethylformamide (DMF) was found to be a more effective extraction solvent than acetonitrile/water (4:3, v/v) or methanol/water (1:1, v/v) mixtures. The precursor, [M+H](+) ions, were detected for the dyes extracted using DMF. The MS(2) and MS(3) spectra also matched those of the standard disperse dyes. Without relying on comparison clothes, disperse dyes extracted from the single fibers (5 mm in length) were successfully identified by LC/LIT-MS(n) and the custom-built database. PMID- 27682412 TI - Design and Application of Multi-functional Electrogenerated Chemiluminescence Imaging Analyzer. AB - A multi-functional eletrogenerated chemiluminescence (ECL) imaging analyzer including both a photomultiplier tube and charged coupled device as detectors has been developed. The ECL imaging analyzer can effectively work for electrochemical study, ECL intensity detection at electrode array, and ECL imaging at bipolar electrodes or electrode array. As an ECL imaging example, an ECL biosensor for visual detection of matrix metalloproteinase 7 in the range from 0.05 to 1 ng/mL is demonstrated. PMID- 27682414 TI - A pH-responsive asymmetric lipid vesicle as drug carrier. AB - In order to increase the loading efficiency of drug carriers, here we demonstrated a microfluidic method to fabricate an asymmetric vesicle, which contains trichloro(1H,1H,2H,2H-perfluoroocty-l)silane (TPS) inner leaflet and lipid outer leaflet. The asymmetric vesicle was characterised by fluorescence microscopy and Fourier transform infra-red spectrum. In vitro cytotoxicity of the vesicles carrying 5-fluorouacil (5-FU) has also been studied. PMID- 27682415 TI - Overcoming procrastination: one-year follow-up and predictors of change in a randomized controlled trial of Internet-based cognitive behavior therapy. AB - Procrastination is a common self-regulatory failure that can have a negative impact on well-being and performance. However, few clinical trials have been conducted, and no follow-up has ever been performed. The current study therefore aimed to provide evidence for the long-term benefits and investigate predictors of a positive treatment outcome among patients receiving Internet-based cognitive behavior therapy (ICBT). A total of 150 self-recruited participants were randomized to guided or unguided ICBT. Self-report measures of procrastination, depression, anxiety, and quality of life were distributed at pre-treatment assessment, post-treatment assessment, and one-year follow-up. Mixed effects models were used to investigate the long-term gains, and multiple linear regression for predictors of a positive treatment outcome, using the change score on the Irrational Procrastination Scale as the dependent variable. Intention-to treat was implemented for all statistical analyses. Large within-group effect sizes for guided and unguided ICBT, Cohen's d = .97-1.64, were found for self report measures of procrastination, together with d = .56-.66 for depression and anxiety. Gains were maintained, and, in some cases, improved at follow-up. Guided and unguided ICBT did not differ from each other, mean differences -.31-1.17, 95% CIs [-2.59-3.22], and none of the predictors were associated with a better result, bs -1.45-1.61, 95% CIs [-3.14-4.26]. In sum, ICBT could be useful and beneficial in relation to managing procrastination, yielding great benefits up to one year after the treatment period has ended, with comparable results between guided and unguided ICBT. PMID- 27682418 TI - A simple technique for suppressor detection in Escherichia coli. AB - To study the viability of a gyrA S83 stop mutation found in an Escherichia coli J53 ciprofloxacin-resistant strain (J53 CipR27), a pBR322 derivative was constructed with a UAG mutation in the bla gene knocking out ampicillin resistance. Ampicillin resistance was restored, suggesting that the strain contains tRNA suppressor activity able to suppress the UAG codon gyrA and allow viability. The method was applied to 22 unique clinical E. coli isolates, and all were found to have low-level suppressor activity. PMID- 27682417 TI - DeaD contributes to Pseudomonas aeruginosa virulence in a mouse acute pneumonia model. AB - DExD/H box RNA helicases play essential roles in various biological processes in prokaryotes and eukaryotes. By screening Pseudomonas aeruginosa strains with mutations in various DExD/H box helicase genes, we identified that deaD was required for bacterial cytotoxicity and virulence in a mouse acute pneumonia model. Compared to a wild-type strain and its complementation strain, the deaD mutant induced less production of proinflammatory cytokines, neutrophil infiltration and lung damage during infection. We further found that the RNA helicase activity of DeaD was required for the expression of type III secretion system (T3SS) genes. Overexpression of ExsA, a master activator of the T3SS, restored the expression of T3SS genes as well as the virulence of the deaD mutant, suggesting that the attenuated virulence of the deaD mutant was mainly due to the defective T3SS. Overall, our results reveal a role of DeaD in the virulence of P. aeruginosa. PMID- 27682419 TI - Association of body mass index and waist circumference with severity of knee osteoarthritis. AB - AIM: The aim of the present study was to investigate the association of the body mass index (BMI) and waist circumference (WC) with the severity of radiographic severity of knee osteoarthritis (rKOA) Methods. A cross-sectional study had been applied during the research which included 150 patients diagnosed at the General Hospital in Uzice and Health Center in Arilje (Serbia). The study included patients over the age of 50 diagnosed with OA according to The European League Against Rheumatism (EULAR) criteria. Data on social-demographic characteristics, health habits, and personal and family histories of the participants were collected through a specific questionnaire designated for this research. The severity of the disease was assessed pursuant to radiological changes using the Kellgren-Lawrence grading scale (K-L). The state of nourishment was assessed according to the BMI and WC. RESULTS: According to multivariate logistic regression analyses, after adjustment on age, sex, marital status, formal education, present occupation, smoking, alcohol consumption and physical activity, higher grades of rKOA (grade III and grade IV) were significantly related to BMI (p = 0.038) and WC (p < 0.001). The association was much stronger for obesity defined as BMI >=30 kg/m2 (p = 0.002) and for abdominal obesity - WC > 102 cm in men and > 88 cm in women (p = 0.009). CONCLUSION: This study showed that obesity defined as BMI >=30 kg/m2 and abdominal obesity are strongly related to K-L of rKOA, the associations being of very similar extent. PMID- 27682421 TI - Bone: The concept of RANKL-independent osteoclastogenesis refuted. PMID- 27682420 TI - Understanding implementation of comprehensive geriatric care programs: a multiple perspective approach is preferred. AB - BACKGROUND: The Prevention and Reactivation Care Program (PReCaP) provides a novel approach targeting hospital-related functional decline among elderly patients. Despite the high expectations, the PReCaP was not effective in preventing functional decline (ADL and iADL) among older patients. Although elderly PReCaP patients demonstrated slightly better cognitive functioning (Mini Mental State Examination; 0.4 [95% confidence interval (CI) 0.2-0.6]), lower depression (Geriatric Depression Scale 15; -0.9 [95% -1.1 to -0.6]), and higher perceived health (Short-form 20; 5.6 [95% CI 2.8-8.4]) 1 year after admission than control patients, the clinical relevance was limited. Therefore, this study aims to identify factors impacting on the effectiveness of the implementation of the PReCaPand geriatric care 'as usual'. METHODS: We conducted semi-structured interviews with 34 professionals working with elderly patients in three hospitals, selected for their comparable patient case mix and different levels of geriatric care. Five non-participatory observations were undertaken during multidisciplinary meetings. Patient files (n = 42), hospital protocols, and care plans were screened for elements of geriatric care. Clinical process data were analysed for PReCaP components. RESULTS: The establishment of a geriatric unit and employment of geriatricians demonstrates commitment to geriatric care in hospital A. Although admission processes are comparable, early identification of frail elderly patients only takes place in hosptial A. Furthermore, nursing care in the hospital A geriatric unit excels with regard to maximizing patient independency, an important predictor for hospital-related functional decline. Transfer nurses play a key role in arranging post-discharge geriatric follow-up care. Geriatric consultations are performed by geriatricians, geriatric nurses, and PReCaP case managers in hospital A. Yet hospital B consultative psychiatric nurses provide similar consultation services. The combination of standardized procedures, formalized communication channels, and advanced computerization contributes significantly to geriatric care in hospital B. Nevertheless, a small size hospital (hospital C) provides informal opportunities for information sharing and decision making, which are essential in geriatric care, given its multidisciplinary nature. CONCLUSIONS: Geriatric care for patients with multimorbidity requires a multidisciplinary approach in a geriatric unit. Geriatric care, which integrates medical and reactivation treatment, by means of early screening of risk factors for functional decline, promotion of physical activity, and adequate discharge planning, potentially reduces the incidence of functional decline in elderly patients. Yet low treatment fidelity played a major role in the ineffective implementation of the PReCaP. Treatment fidelity issues are caused by various factors, including the complexity of projects, limited attention for implementation, and inadequate interdisciplinary communication. (c) 2016 The Authors The International Journal of Health Planning and Management Published by John Wiley & Sons Ltd. PMID- 27682423 TI - Fruit and Vegetables Consumption: A Pointer for Cholangiocarcinoma Prevention in Northeast Thailand, the Highest Incidence Area in the World. AB - Cholangiocarcinoma (CCA) caused by opisthorchiasis is a specific public health problem in the Greater Mekong subregional countries. The Northeast Thailand is considered a world's prime area of CCA. Many epidemiological studies found the association between fruit and vegetables consumption and CCA, but their results were inconclusive. Therefore, this meta-analysis aimed to investigate the relationship between fruit and vegetables consumption and CCA prevention in the Northeast Thailand. The authors conducted a comprehensive search of scholarships on MEDLINE, EMBASE, and SCOPUS published during 1990 and 2015. Selected studies about fruit and vegetables consumption and CCA were analyzed. The fixed-effect model was used to estimate pool odds ratios for the consumption vs. nonconsumption. Based on a meta-analysis, consumption of mixed fruit [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.65-0.96], mixed vegetables (OR = 0.61; 95% CI: 0.50-0.75), and combined fruit and vegetables (OR = 0.68; 95% CI: 0.57-0.80) was associated with the reduction of CCA risk statistically. These findings support that fruit and vegetables consumption is associated with CCA risk reduction. If implemented in a larger geographical area, the study will shed light on possibilities to future reduction of CCA. Educators can replicate the study to solve CCA or other types of cancer and discover the best practice. PMID- 27682422 TI - Nationwide Distribution of Bovine Influenza D Virus Infection in Japan. AB - Cattle are major reservoirs of the provisionally named influenza D virus, which is potentially involved in the bovine respiratory disease complex. Here, we conducted a serological survey for the influenza D virus in Japan, using archived bovine serum samples collected during 2010-2016 from several herds of apparently healthy cattle in various regions of the country. We found sero-positive cattle across all years and in all the prefectural regions tested, with a total positivity rate of 30.5%, although the positivity rates varied among regions (13.5-50.0%). There was no significant difference in positivity rates for Holstein and Japanese Black cattle. Positivity rates tended to increase with cattle age. The herds were clearly divided into two groups: those with a high positive rate and those with a low (or no) positive rate, indicating that horizontal transmission of the virus occurs readily within a herd. These data demonstrate that bovine influenza D viruses have been in circulation for at least 5 years countrywide, emphasizing its ubiquitous distribution in the cattle population of Japan. PMID- 27682425 TI - Nurses' perspectives on moral distress: A Q methodology approach. AB - BACKGROUND: Moral distress occurs when nurses experience ethical dilemmas. Issues related to these dilemmas are addressed in some nursing education courses. Nurses' reaction to dilemma such as moral distress is relatively less noticed. OBJECTIVE: This study aimed to identify and describe the various types of perceptions of moral distress exhibited by nurses. RESEARCH DESIGN: This study applied Q methodology to explore the perspectives of nurses regarding moral distress. Data were collected in two stages. First, in-depth interviews were conducted to collect nurses' opinions. Sentences that best fit the concepts of moral distress were extracted for the construction of Q statements. Second, nurses subjectively ranked these Q statements so that the relevant severity of moral distress could be determined using Q sorts. The study participants were nurses at a regional teaching hospital in northeast Taiwan. A total of 60 participants were invited to rank 40 moral distress Q statements. Ethical considerations: The study protocol was approved by the institutional review board of National Yang-Ming University Hospital. Only the participants who signed an informed consent form participated in the study. The respondents' right to withdraw from the study was respected. FINDINGS: Five types of responses were identified regarding the nurses' perspectives. These types were "conflict with personal values," "excessive of workload," "curbing of autonomy," "constraint engendered by organizational norms," and "self-expectation frustration." CONCLUSION: The findings regarding nurses' experiences of moral distress can be used to construct multifaceted policies and solutions and to incorporate ethical education in training programs. PMID- 27682424 TI - The Usefulness of the Delta Neutrophil Index for Predicting Superimposed Pneumonia in Patients with Acute Decompensated Heart Failure in the Emergency Department. AB - BACKGROUND: Although respiratory infections, such as pneumonia, have long been recognized as precipitators of exacerbation in patients with acute decompensated heart failure (ADHF), identifying signs of concomitant pneumonia in ADHF is a clinical diagnostic challenge. We evaluated the predictive value of the delta neutrophil index (DNI), a new indicator for immature granulocytes, for diagnosing superimposed pneumonia in patients presenting with ADHF in the emergency department (ED). METHODS: This was a retrospective and observational study of consecutive patients (>18 years old) diagnosed with an ADHF in the ED over a 7 month period. Patients were categorized into either the ADHF group or the ADHF with pneumonia group. DNI, serum white blood cell (WBC), C-reactive protein (CRP), and beta-natriuretic peptide (BNP) were measured upon ED arrival. RESULTS: The ADHF with pneumonia group included 30 patients (20.4%). Median initial DNI, WBC, and CRP were significantly higher in the ADHF with pneumonia group [0% vs. 1.8%, p<0.001, 8,200 cells/mL vs. 10,470 cells/mL, p<0.001, and 0.56 mg/dL vs. 6.10 mg/dL, p<0.001]. Multiple logistic regression analyses showed that only initial DNI significantly predicted the presence of superimposed pneumonia in patients with ADHF. In the receiver operating characteristic curves for initial DNI, WBC, and CRP for differentiating superimposed pneumonia in ADHF patients, the area under curve (AUC) of DNI (0.916 [95% confidence interval 0.859-0.955]) was good. AUC of DNI was significantly higher than AUC of CRP and WBC [0.828 and 0.715] (DNI vs. CRP, p = 0.047 and DNI vs. WBC, p<0.001). CONCLUSIONS: Initial DNI, which was measured upon ED arrival, was significantly higher in the ADHF with pneumonia group than in the ADHF group. The initial DNI's ability of prediction for ADHF with superimposed pneumonia in the ED was good and it was better than those of serum WBC and CRP. Therefore, DNI may serve as a convenient and useful marker for early diagnosis of superimposed pneumonia in patients with ADHF in the ED. PMID- 27682426 TI - Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. AB - The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naive infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials. PMID- 27682429 TI - Remarkable Anion-Dependent Spin-State Switching in Diiron(III) MU-Hydroxo Bisporphyrins: What Role do Counterions Play? AB - Addition of 2,4,6-trinitrophenol (HTNP) to an ethene-bridged diiron(III) MU-oxo bisporphyrin (1) in CH2 Cl2 initially leads to the formation of diiron(III) MU hydroxo bisporphyrin (2?TNP) with a phenolate counterion that, after further addition of HTNP or dissolution in a nonpolar solvent, converts to a diiron(III) complex with axial phenoxide coordination (3?(TNP)2 ). The progress of the reaction from MU-oxo to MU-hydroxo to axially ligated complex has been monitored in solution by using 1 H NMR spectroscopy because their signals appear in three different and distinct spectral regions. The X-ray structure of 2?TNP revealed that the nearly planar TNP counterion fits perfectly within the bisporphyrin cavity to form a strong hydrogen bond with the MU-hydroxo group, which thus stabilizes the two equivalent iron centers. In contrast, such counterions as I5 , I3 , BF4 , SbF6 , and PF6 are found to be tightly associated with one of the porphyrin rings and, therefore, stabilize two different spin states of iron in one molecule. A spectroscopic investigation of 2?TNP has revealed the presence of two equivalent iron centers with a high-spin state (S=5/2) in the solid state that converts to intermediate spin (S=3/2) in solution. An extensive computational study by using a range of DFT methods was performed on 2?TNP and 2+ , and clearly supports the experimentally observed spin flip triggered by hydrogen-bonding interactions. The counterion is shown to perturb the spin-state ordering through, for example, hydrogen-bonding interactions, switched positions between counterion and axial ligand, ion-pair interactions, and charge polarization. The present investigation thus provides a clear rationalization of the unusual counterion-specific spin states observed in the MU-hydroxo bisporphyrins that have so far remained the most outstanding issue. PMID- 27682428 TI - Older People's External Residential Assessment Tool (OPERAT): a complementary participatory and metric approach to the development of an observational environmental measure. AB - BACKGROUND: The potential for environmental interventions to improve health and wellbeing has assumed particular importance in the face of unprecedented population ageing. However, presently observational environmental assessment tools are unsuitable for 'all ages'. This article describes the development of the Older People's External Residential Assessment Tool (OPERAT). METHODS: Potential items were identified through review and consultation with an Expert Advisory Group. Items were ranked according the importance ascribed to them by older people who responded to a survey distributed by 50+ forum in Wales (N = 545). 40 highly ranked items were selected for the OPERAT pilot. An observational assessment was conducted in 405 postcodes in Wales. Items validated with data from a survey of older residents (N = 500) in the postcode areas were selected for statistical modelling (Kendall's Tau-b, p < .05). Data reduction techniques (exploratory factor analysis with Geomin rotation) identified the underlying factor structure of OPERAT. Items were weighted (Thurstone scaling approach) and scores calculated for each domain. Internal consistency: all items were tested for scale-domain total correlation (Spearman's rank). Construct validity: correlation analysis examined the associations between domains and the extent to which participants enjoyed living in the area, felt that it was a desirable place to live, or felt safe at night or during the day (Spearman's rank). Usability: analysis of variance compared mean OPERAT domain scores between neighbourhoods that were homogenous in terms of (a) deprivation (quintiles of the Townsend Index) and (b) geographic settlement type. Inter-rater reliability: Krippendorff's alpha was used to evaluate inter-rater consistency in ten postcode areas. RESULTS: A four factor model was selected as the best interpretable fit to the data. The domains were named Natural Elements, Incivilities and Nuisance; Navigation and Mobility; and Territorial Functioning. Statistical tests demonstrated good internal consistency, convergent validity, utility and inter rater reliability. CONCLUSIONS: Participatory approaches to research and robust statistical testing are not mutually exclusive. OPERAT can be used to assess the suitability of external residential environments for older people with different physical and cognitive capacities, living in rural or urban areas. OPERAT can be used to help plan residential environments that are friendly for all ages. PMID- 27682427 TI - Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: prospectively patient-reported outcome measures in breast cancer patients. AB - INTRODUCTION: This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy. METHOD: Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score. RESULTS: Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05). CONCLUSION: In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible. PMID- 27682431 TI - Closed head experimental traumatic brain injury increases size and bone volume of callus in mice with concomitant tibial fracture. AB - Concomitant traumatic brain injury (TBI) and long bone fracture are commonly observed in multitrauma and polytrauma. Despite clinical observations of enhanced bone healing in patients with TBI, the relationship between TBI and fracture healing remains poorly understood, with clinical data limited by the presence of several confounding variables. Here we developed a novel trauma model featuring closed-skull weight-drop TBI and concomitant tibial fracture in order to investigate the effect of TBI on fracture healing. Male mice were assigned into Fracture + Sham TBI (FX) or Fracture + TBI (MULTI) groups and sacrificed at 21 and 35 days post-injury for analysis of healing fractures by micro computed tomography (MUCT) and histomorphometry. MUCT analysis revealed calluses from MULTI mice had a greater bone and total tissue volume, and displayed higher mean polar moment of inertia when compared to calluses from FX mice at 21 days post injury. Histomorphometric results demonstrated an increased amount of trabecular bone in MULTI calluses at 21 days post-injury. These findings indicate that closed head TBI results in calluses that are larger in size and have an increased bone volume, which is consistent with the notion that TBI induces the formation of a more robust callus. PMID- 27682432 TI - Long bone histology of the subterranean rodent Bathyergus suillus (Bathyergidae): ontogenetic pattern of cortical bone thickening. AB - Patterns of bone development in mammals are best known from terrestrial and cursorial groups, but there is a considerable gap in our understanding of how specializations for life underground affect bone growth and development. Likewise, studies of bone microstructure in wild populations are still scarce, and they often include few individuals and tend to be focused on adults. For these reasons, the processes generating bone microstructural variation at intra- and interspecific levels are not fully understood. This study comprehensively examines the bone microstructure of an extant population of Cape dune molerats, Bathyergus suillus (Bathyergidae), the largest subterranean mammal endemic to the Western Cape of South Africa. The aim of this study is to investigate the postnatal bone growth of B. suillus using undecalcified histological sections (n = 197) of the femur, humerus, tibia-fibula, ulna and radius, including males and females belonging to different ontogenetic and reproductive stages (n = 42). Qualitative histological features demonstrate a wide histodiversity with thickening of the cortex mainly resulting from endosteal and periosteal bone depositions, whilst there is scarce endosteal resorption and remodeling throughout ontogeny. This imbalanced bone modeling allows the tissues deposited during ontogeny to remain relatively intact, thus preserving an excellent record of growth. The distribution of the different bone tissues observed in the cortex depends on ontogenetic status, anatomical features (e.g. muscle attachment structures) and location on the bone (e.g. anterior or lateral). The type of bone microstructure and modeling is discussed in relation to digging behavior, reproduction and physiology of this species. This study is the first histological assessment describing the process of cortical thickening in long bones of a fossorial mammal. PMID- 27682430 TI - [Iron deficiency, thrombocytosis and thromboembolism]. AB - Iron deficiency, the most common nutritional deficiency worldwide, is often associated with reactive thrombocytosis. Although secondary thrombocytosis is commonly considered to be harmless, there is accumulating evidence that elevated platelet counts, especially in the setting of iron deficiency, can lead to an increased thromboembolic risk in both arterial and venous systems. Here we present the mechanisms of iron deficiency-induced thrombocytosis and summarize its clinical consequences especially in patients with inflammatory bowel diseases, chronic kidney disease or cancer. We hypothesize that iron deficiency is an underestimated thromboembolic risk factor, and that iron replacement therapy can become an effective preventive strategy in a variety of clinical settings. PMID- 27682434 TI - Sleep duration and cognitive impairment in older adults. PMID- 27682433 TI - Impact of tooth loss on walking speed decline over time in older adults: a population-based cohort study. AB - BACKGROUND: Tooth loss has been linked to poor health such as chronic diseases and mobility limitations. Prospective evidence on the association between tooth loss and walking speed decline is however lacking. AIMS: To examine the impact of tooth loss on walking speed over time and explore whether inflammation may account for this association. METHODS: This study included 2695 persons aged 60 years and older, who were free from severe mobility limitation at baseline. Information on dental status was assessed through self-report during the nurse interview at baseline. Walking speed baseline and at 3- and 6-year follow-ups was assessed when participants walked at their usual pace. Covariates included age, sex, education, lifestyle-related factors, and chronic diseases. Blood samples were taken, and C-reactive protein (CRP) was tested. RESULTS: At baseline, 389 (13.1 %) participants had partial tooth loss and 204 (6.9 %) had complete tooth loss. Mixed-effects models showed that tooth loss was associated with a greater decline in walking speed over time after adjustment for lifestyle-related factors and chronic diseases (p = 0.001 for interaction between time and tooth loss on walking speed decline); however, when further adjusting for inflammation (CRP), the association was attenuated and no longer significant. CONCLUSION: Tooth loss was associated with an accelerated decline in walking speed in older adults. Inflammation may play a role in the association between tooth loss and walking speed decline. PMID- 27682435 TI - Gait speed response to aerobic versus resistance exercise training in older adults. AB - BACKGROUND: Little is known about the comparative effect of aerobic training (AT) versus resistance training (RT) on gait speed, a strong predictor of disability. AIMS: To compare the effect of AT versus RT on gait speed and other functional measures. METHODS: Overweight and obese [body mass index (BMI) >=27.0 kg/m2] sedentary men and women aged 65-79 years engaged in 5 months of either 4 days/weeks moderate-intensity treadmill walking, AT, (n = 44) or 3 days/weeks moderate-intensity RT (n = 56). Usual-pace gait speed, fast-pace gait speed and short physical performance battery (SPPB) were evaluated in all participants before and after training. Peak oxygen consumption (VO2peak) was assessed in AT participants only, and knee extensor strength was assessed in RT participants. RESULTS: Both AT and RT resulted in clinically significant improvements in usual pace gait speed (0.08 +/- 0.14 and 0.08 +/- 0.17 m/s, respectively, both p < 0.05) and SPPB (0.53 +/- 1.40 and 0.53 +/- 1.20 points, both p < 0.05) and chair rise time (-1.2 +/- 3.2 and -1.7 +/- 3.0 s, p < 0.05). Only AT improved fast-pace gait speed (0.11 +/- 0.10 m/s, p < 0.05). In the RT participants, lower baseline knee strength was associated with less improvement in usual-pace gait speed. In AT participants, lower baseline VO2peak was associated with less improvement in chair rise time and self-reported disability. DISCUSSION: While both AT and RT improved usual-pace gait speed, only AT improved fast-pace gait speed. Lower baseline fitness was associated with less improvement with training. CONCLUSION: Research to directly compare which mode of training elicits the maximum improvement in older individuals with specific functional deficits could lead to better intervention targeting. PMID- 27682436 TI - Photosynthetic activity and proteomic analysis highlights the utilization of atmospheric CO2 by Ulva prolifera (Chlorophyta) for rapid growth. AB - Free-floating Ulva prolifera is one of the causative species of green tides. When green tides occur, massive mats of floating U. prolifera thalli accumulate rapidly in surface waters with daily growth rates as high as 56%. The upper thalli of the mats experience environmental changes such as the change in carbon source, high salinity, and desiccation. In this study, the photosynthetic performances of PSI and PSII in U. prolifera thalli exposed to different atmospheric carbon dioxide (CO2 ) levels were measured. Changes in photosynthesis within salinity treatments and dehydration under different CO2 concentrations were also analyzed. The results showed that PSII activity was enhanced as CO2 increased, suggesting that CO2 assimilation was enhanced and U. prolifera thalli can utilize CO2 in the atmosphere directly, even when under moderate stress. In addition, changes in the proteome of U. prolifera in response to salt stress were investigated. Stress-tolerance proteins appeared to have an important role in the response to salinity stress, whereas the abundance of proteins related to metabolism showed no significant change under low salinity treatments. These findings may be one of the main reasons for the extremely high growth rate of free-floating U. prolifera when green tides occur. PMID- 27682437 TI - Weekday sunlight exposure, but not vitamin D intake, influences the association between vitamin D receptor genotype and circulating concentration 25 hydroxyvitamin D in a pan-European population: the Food4Me study. AB - SCOPE: Little is known about diet- and environment-gene interactions on 25 hydroxyvitamin D (25(OH)D concentration. This cross-sectional study aimed to investigate (i) predictors of 25(OH)D concentration and relationships with vitamin D genotypes and (ii) whether dietary vitamin D intake and sunlight exposure modified these relationships. METHODS AND RESULTS: Participants from the Food4Me study (n = 1312; age 18-79) were genotyped for vitamin D receptor (VDR) and vitamin D binding protein at baseline and a genetic risk score was calculated. Dried blood spot samples were assayed for 25(OH)D concentration and dietary and lifestyle information collected. Circulating 25(OH)D concentration was lower with increasing genetic risk score, lower in females than males, higher in supplement users than non-users and higher in summer than winter. Carriage of the minor VDR allele was associated with lower 25(OH)D concentration in participants with the least sunlight exposure. Vitamin D genotype did not influence the relationship between vitamin D intake and 25(OH)D concentration. CONCLUSION: Age, sex, dietary vitamin D intake, country, sunlight exposure, season, and vitamin D genetic risk score were associated with circulating 25(OH)D concentration in a pan-European population. The relationship between VDR genotype and 25(OH)D concentration may be influenced by weekday sunlight exposure but not dietary vitamin D intake. PMID- 27682438 TI - Malaria infection and anaemia in HIV-infected children in Mutengene, Southwest Cameroon: a cross sectional study. AB - BACKGROUND: Malaria is one of the leading causes of morbidity and mortality in children and HIV infection as well as other factors may worsen the situation. This study was aimed at determining the factors influencing malaria parasite prevalence and density as well as anaemia in HIV-infected children in Mutengene, Cameroon from November, 2012 to April, 2013. METHODS: A semi-structured questionnaire was used to record information on socio-demographic factors and use of preventive measures by caregivers of HIV-infected children aged 1-15 years and of both sexes. Venous blood was collected; blood films were prepared and Giemsa stained for parasite detection and speciation. Haemoglobin concentration was measured and the anaemic status determined. Data was analysed using Epi Info 7 software. RESULTS: A total of 234 children were studied. The overall malaria parasite prevalence was 24.8 % (58) and was significantly higher (31.9 %, P = 0 .004) in females, those who did not implement any preventive measure at all (66.7 %, P = 0.03) and children who used antiretroviral therapy (ART) (28.6 %, P = 0.02) when compared with their respective counterparts. Geometric mean parasite density (GMPD) was significantly higher (3098.4, P = 0.02) in children who presented with fever, had CD4 T cells >=500 cells/MUL (491.3, P = 0.003) and those with moderate anaemia (1658.8, P = 0.03) than their respective counterparts. Although there was no significant difference, GMPD was however higher in males (549.0); those not on ART (635.0) and highest in children <5 years old (633.0) than their respective counterparts. The overall prevalence of anaemia was 49.6 % (116). The value was significantly highest (58.3 %, P = 0.01) in the 11-15 years age group; those with CD4 T cell level 200-499 (72.7 %, P = 0.001) and children with fever (85.7 %, P = 0.01). CONCLUSION: Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anaemia on prescription of ART could likely improve the health conditions of HIV-infected children thus avoiding malaria-related morbidity and mortality. PMID- 27682439 TI - Reduced metabolic function and structural alterations in inherited retinal dystrophies: investigating the effect of peripapillary vessel oxygen saturation and vascular diameter on the retinal nerve fibre layer thickness. AB - PURPOSE: To evaluate the relationship between the peripapillary metabolic alterations [retinal vessel Oximetry (RO)] and the structural findings [retinal vessel diameter and retinal nerve fibre layer thickness (RNFL)] in patients with inherited retinal dystrophies (IRD). METHODS: Patients with IRD [24 patients with rod-cone dystrophy (RCD), 15 patients with cone-rod dystrophy, 13 patients with inherited maculopathy] and 18 age-matched controls, who underwent RO imaging and spectral domain optical coherence tomography, were included. The average and quadrant oxygen saturation in all four major peripapillary retinal arterioles (A SO2 ) and venules (V-SO2 ) were measured, and their difference (A-V SO2 ) was calculated. The corresponding retinal vessel diameter of these arterioles (D-A) and venules (D-V) was measured. The data were compared to the peripapillary RNFL thickness within the IRD subgroups and to the data obtained in the controls. RESULTS: In general, patients with IRD had higher average V-SO2 values when compared to controls (p <= 0.029). Rod-cone dystrophy (RCD) patients differed from controls, but also from patients with other IRDs, when the average and quadrant oxygen saturation values (A-SO2 and V-SO2 ) were evaluated (p <= 0.026). Within the RCD group, the correlations of RNFL thickness to V-SO2 , A-V SO2 , D-A and D-V were significant (p <= 0.030), thus indicating a different relationship between the RNFL thickness and the examined parameters, when compared to the other groups. CONCLUSION: It becomes evident from our combined metabolic structural approach that a prediction model, to identify which individual is at risk of developing a photoreceptor degeneration of RCD type, can be proposed. It will take into account the peripapillary retinal oxygen saturation, the retinal vessel diameter and the RNFL thickness values. PMID- 27682441 TI - Reversible Right Heart Failure in Scurvy Rediscovery of an Old Observation. PMID- 27682440 TI - Risk Factors for Incident Hospitalized Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women. AB - BACKGROUND: Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. METHODS AND RESULTS: We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. CONCLUSIONS: In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611. PMID- 27682443 TI - Spatial Overlap of Grey Seals and Fisheries in Irish Waters, Some New Insights Using Telemetry Technology and VMS. AB - Seals and humans often target the same food resource, leading to competition. This is of mounting concern with fish stocks in global decline. Grey seals were tracked from southeast Ireland, an area of mixed demersal and pelagic fisheries, and overlap with fisheries on the Celtic Shelf and Irish Sea was assessed. Overall, there was low overlap between the tagged seals and fisheries. However, when we separate active (e.g. trawls) and passive gear (e.g. nets, lines) fisheries, a different picture emerged. Overlap with active fisheries was no different from that expected under a random distribution, but overlap with passive fisheries was significantly higher. This suggests that grey seals may be targeting the same areas as passive fisheries and/or specifically targeting passive gear. There was variation in foraging areas between individual seals suggesting habitat partitioning to reduce intra-specific competition or potential individual specialisation in foraging behaviour. Our findings support other recent assertions that seal/fisheries interactions in Irish waters are an issue in inshore passive fisheries, most likely at the operational and individual level. This suggests that seal population management measures would be unjustifiable, and mitigation is best focused on minimizing interactions at nets. PMID- 27682444 TI - beta-defensin CNV is not associated with susceptibility to Candida albicans infections in Sardinian APS I patients. AB - OBJECTIVE: The aim of this study was to investigate whether a variation in the genomic copy number (CNV) of the beta-defensin cluster could be associated with the pre-disposition to chronic mucocutaneous candidiasis (CMC) in Sardinian APECED patients. SUBJECTS AND METHODS: The beta-defensin copy number variation was determined by MLPA analysis in 18 Sardinian APECED patients with CMC and in 21 Sardinian controls. Statistical analyses were performed with one-way ANOVA test. RESULTS: No statistically significant results were observed between the patients and controls groups. CONCLUSIONS: According to the results we have obtained, it appears that either beta-defensin genomic CNV is not a modifier locus for CMC susceptibility in APECED patients, or any effect is too small for it to be detected using such sample size. An extensive study on APECED patients from different geographical areas might reveal the real implication of the beta defensin CNV in the susceptibility to Candida albicans infections. PMID- 27682442 TI - PROTECT - trial: a multicentre prospective pragmatic RCT and health economic analysis of the effect of tailored repositioning to prevent pressure ulcers - study protocol. AB - AIM: The aims of this trial were as follows: (1) to compare the (cost-) effectiveness of a turning and repositioning system and an algorithm for a tailored repositioning vs. usual care to improve reposition frequency in patients at risk; and (2) to compare the (cost-) effectiveness of standardized incontinence care vs. usual care. BACKGROUND: Pressure ulcers are a serious and common problem for hospitalized patients. In many countries, pressure ulcers are recognized as a national health issue and governments designate pressure ulcers as one of the most important sentinel events for health care. International guidelines recommend the use of pressure redistributing support surfaces, systematic patient repositioning and preventive skin care to prevent pressure ulcers. Interventions should be patient-tailored and based on a thorough assessment of both the patient and contextual risk factors. There is a lack of rigorous research addressing the effectiveness of a turning and repositioning system and it is unclear how to tailor the frequency and posture to specific patient needs. DESIGN: Multicentre, cluster, three-arm, randomized, controlled pragmatic trial and a cost-effectiveness analysis. The ward is the unit of randomization. METHODS: Tailored repositioning, the use of a device to facilitate patient repositioning and an optimal procedure for incontinence care will be combined. Participating wards will be intensive care units, geriatric and rehabilitation wards. A sample size calculation was performed (80% power, alpha = 0.05). This study is approved by the Ethics Committee (February 2016). DISCUSSION: Data collection is currently ongoing. The results are expected to be obtained in March 2017. PMID- 27682445 TI - Spigelian hernia A series of cases and literature review. AB - AIM: The aim of this case series is to describe the pathophysiological, clinical, and radiological features of Spigelian hernias, and to describe their modern surgical management. MATERIAL OF STUDY: We describe the clinical management of four cases of Spigelian hernias, and we discuss the main issues and controversies in the current scientific literature. RESULTS: In all the cases the clinical suspect arouses during the clinical examination of the patients, and it was confirmed through imaging techniques. All cases were treated surgically by an open approach; no intraoperative or postoperative complications occurred, and no recurrences were registered. DISCUSSION: Our experience and the literature review that we carried out confirm that Spigelian hernia is a rare condition, and its diagnosis should always be based on a thorough clinical examination and possibly a ultrasound or computed tomography, which are important for the study of the exact anatomical features of the defect, and for the planning of the adequate operative approach. The laparoscopic technique is effective but used in few reference centers, both for the rarity of the disease and the long learning curve, whereas the open surgical correction is the most common approach, with excellent results, especially in cases where urgent repair is needed. CONCLUSION: The surgical treatment of Spigelian hernias has excellent results when a thorough clinical - radiological evaluation is carried out, and the appropriate surgical approach is chosen. KEY WORDS: Abdominal wall, Spigelian hernia, Surgery. PMID- 27682446 TI - Bioactive glass-based surfaces induce differential gene expression profiling of osteoblasts. AB - The ability of Biosilicate(r) with two crystalline phases (BioS-2P) to drive osteoblast differentiation encourages the investigation of the cellular mechanisms involved in this process. Then, the aim of our study was to analyze the large-scale gene expression of osteoblasts grown on BioS-2P compared with Bioglass(r) 45S5 (45S5). Osteoblasts differentiated from rat bone marrow mesenchymal stem cells were cultured under osteogenic conditions on BioS-2P, 45S5 and polystyrene (control). After 10 days, the expression of 23,794 genes was analyzed using mRNA Sequencing and the data were validated by real-time PCR. The BioS-2P exhibited 5 genes upregulated and 3 downregulated compared with 45S5. Compared with control, BioS-2P upregulated 15 and downregulated 11 genes, while 45S5 upregulated 25 and downregulated 21 genes. Eight genes were commonly upregulated and 4 downregulated by both bioactive glasses. In conclusion, our results demonstrated that bioactive glasses affect the gene expression profiling of osteoblasts. Most of the regulated genes by both BioS-2P and 45S5 are associated with the process of mineralization highlighting their osteostimulation property that is, at least in part, derived from the ability to modulate the intracellular machinery to promote osteoblast genotype expression. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 419-423, 2017. PMID- 27682447 TI - A qualitative synthesis of the positive and negative impacts related to delivery of peer-based health interventions in prison settings. AB - BACKGROUND: Peer interventions involving prisoners in delivering peer education and peer support in a prison setting can address health need and add capacity for health services operating in this setting. This paper reports on a qualitative synthesis conducted as part of a systematic review of prison-based peer interventions. One of the review questions aimed to investigate the positive and negative impacts of delivering peer interventions within prison settings. This covered organisational and process issues relating to peer interventions, including prisoner and staff views. METHODS: A qualitative synthesis of qualitative and mixed method studies was undertaken. The overall study design comprised a systematic review involving searching, study selection, data extraction and validity assessment. Studies reporting interventions with prisoners or ex-prisoners delivering education or support to prisoners resident in any type of prison or young offender institution, all ages, male and female, were included. A thematic synthesis was undertaken with a subset of studies reporting qualitative data (n = 33). This involved free coding of text reporting qualitative findings to develop a set of codes, which were then grouped into thematic categories and mapped back to the review question. RESULTS: Themes on process issues and wider impacts were grouped into four thematic categories: peer recruitment training and support; organisational support; prisoner relationships; prison life. There was consistent qualitative evidence on the need for organisational support within the prison to ensure smooth implementation and on managing security risks when prisoners were involved in service delivery. A suite of factors affecting the delivery of peer interventions and the wider organisation of prison life were identified. Alongside reported benefits of peer delivery, some reasons for non-utilisation of services by other prisoners were found. There was weak qualitative evidence on wider impacts on the prison system, including better communication between staff and prisoners. Gaps in evidence were identified. CONCLUSIONS: The quality of included studies limited the strength of the conclusions. The main conclusion is that peer interventions cannot be seen as independent of prison life and health services need to work in partnership with prison services to deliver peer interventions. More research is needed on long term impacts. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349 . PMID- 27682448 TI - "The Emperor's new clothes": discourse analysis on how the patient is constructed in the new Swedish Patient Act. AB - The Swedish welfare debate increasingly focuses on market liberal notions and its healthcare perspective aims for more patient-centered care. This article examines the new Swedish Patient Act describing and analyzing how the patient is constructed in government documents. This study takes a Foucauldian discourse analysis approach following Willig's analysis guide. The act contains an entitlement discourse for patients and a requirement discourse for healthcare personnel. These two discourses are governed by a values-based healthcare discourse. Neo-liberal ideology, in the form of New Public Management discourse, focusing on the value of efficiency and competition, is given a hegemonic position as laws and regulations are used to strengthen it. The new Swedish Patient Act seems to further strengthen this development. The Act underlines the increased entitlement for patients, but it is not legally binding as it offers patients only indirect entitlement to influence and control their care. To safeguard the patient's entitlement under the Patient Act, healthcare personnel should be made aware of the contents of the Act, so that they can contribute to the creation of systems and working methods that facilitate respect of the Act's provisions in daily healthcare work. PMID- 27682449 TI - Young asteroidal fluid activity revealed by absolute age from apatite in carbonaceous chondrite. AB - Chondritic meteorites, consisting of the materials that have formed in the early solar system (ESS), have been affected by late thermal events and fluid activity to various degrees. Determining the timing of fluid activity in ESS is of fundamental importance for understanding the nature, formation, evolution and significance of fluid activity in ESS. Previous investigations have determined the relative ages of fluid activity with short-lived isotope systematics. Here we report an absolute 207Pb/206Pb isochron age (4,450+/-50 Ma) of apatite from Dar al Gani (DaG) 978, a type ~3.5, ungrouped carbonaceous chondrite. The petrographic, mineralogical and geochemical features suggest that the apatite in DaG 978 should have formed during metamorphism in the presence of a fluid. Therefore, the apatite age represents an absolute age for fluid activity in an asteroidal setting. An impact event could have provided the heat to activate this young fluid activity in ESS. PMID- 27682450 TI - Extracting quantum coherence via steering. AB - As the precious resource for quantum information processing, quantum coherence can be created remotely if the involved two sites are quantum correlated. It can be expected that the amount of coherence created should depend on the quantity of the shared quantum correlation, which is also a resource. Here, we establish an operational connection between coherence induced by steering and the quantum correlation. We find that the steering-induced coherence quantified by such as relative entropy of coherence and trace-norm of coherence is bounded from above by a known quantum correlation measure defined as the one-side measurement induced disturbance. The condition that the upper bound saturated by the induced coherence varies for different measures of coherence. The tripartite scenario is also studied and similar conclusion can be obtained. Our results provide the operational connections between local and non-local resources in quantum information processing. PMID- 27682451 TI - Science Outside the Lab: Helping Graduate Students in Science and Engineering Understand the Complexities of Science Policy. AB - Helping scientists and engineers challenge received assumptions about how science, engineering, and society relate is a critical cornerstone for macroethics education. Scientific and engineering research are frequently framed as first steps of a value-free linear model that inexorably leads to societal benefit. Social studies of science and assessments of scientific and engineering research speak to the need for a more critical approach to the noble intentions underlying these assumptions. "Science Outside the Lab" is a program designed to help early-career scientists and engineers understand the complexities of science and engineering policy. Assessment of the program entailed a pre-, post-, and 1 year follow up survey to gauge student perspectives on relationships between science and society, as well as a pre-post concept map exercise to elicit student conceptualizations of science policy. Students leave Science Outside the Lab with greater humility about the role of scientific expertise in science and engineering policy; greater skepticism toward linear notions of scientific advances benefiting society; a deeper, more nuanced understanding of the actors involved in shaping science policy; and a continued appreciation of the contributions of science and engineering to society. The study presents an efficacious program that helps scientists and engineers make inroads into macroethical debates, reframe the ways in which they think about values of science and engineering in society, and more thoughtfully engage with critical mediators of science and society relationships: policy makers and policy processes. PMID- 27682452 TI - Relationship between venous drainage subtypes and sub-arachnoid hemorrhage subtypes: a meta-analysis. AB - BACKGROUND: To investigate whether associations exist between venous drainage subtypes (types I, II, and III) and the risk of subarachnoid hemorrhage subtypes. METHODS: Published case-control and case series from 2010 to 2014 which met all the inclusion criteria for the meta-analysis were selected and subjected to rigorous statistical analysis. RESULTS: A total of 11 studies with an overall patient population (case and controls) of 891 were involved in the study. Types I and II venous drainage had odds against peri-mesencephalic subarachnoid hemorrhage. The odds were in favor of type III venous drainage and peri mesencephalic sub-arachnoid hemorrhage and idiopathic sub-arachnoid hemorrhage (ISAH). CONCLUSIONS: Type I deep venous drainage may not be associated with the risks of peri-mesencephalic subarachnoid hemorrhage and ISAH, however, types II and III may be associated with high risk of peri-mesencephalic subarachnoid hemorrhage and ISAH, respectively. PMID- 27682453 TI - An Icosahedral Quasicrystal and Its 1/0 Crystalline Approximant in the Ca-Au-Al System. AB - A new icosahedral quasicrystalline phase, CaAu4.5-xAl1.5+x [0.11 <= x <= 0.40(6); CaAu4.4Al1.6, aQC = 5.383(4) A, and Pm3 5], and its lowest-order 1/0 cubic crystalline approximant phase, CaAu3+xAl1-x [0 <= x <= 0.31(1); a = 9.0766(5) 9.1261(8) A, Pa3 (No. 205), and Pearson symbol cP40], have been discovered in the Ca-poor region of the Ca-Au-Al system. In the crystalline approximant, eight [Au3 xAl1+x] tetrahedra fill the unit cell, and each tetrahedron is surrounded by four Ca atoms, thus forming a three-dimensional network of {Ca4/4[Au3-xAl1+x]} tetrahedral stars. A computational study of Au and Al site preferences concurs with the experimental results, which indicate a preference for near-neighbor Au Al interactions over Au-Au and Al-Al interactions. Analysis of the electronic density of states and the associated crystal orbital Hamilton population curves was used to rationalize the descriptions of CaAu4.5-xAl1.5+x [0.11 <= x <= 0.46(6)] and CaAu3+xAl1-x [0 <= x <= 0.31(1)] as polar intermetallic species, whereby Ca atoms engage in polar covalent bonding with the electronegative, electron-deficient [Au3-xAl1+x] tetrahedral clusters and the observed phase width of the crystalline approximant. PMID- 27682454 TI - Efficient Compact-Layer-Free, Hole-Conductor-Free, Fully Printable Mesoscopic Perovskite Solar Cell. AB - A compact-layer-free, hole-conductor-free, fully printable mesoscopic perovskite solar cell presents a power conversion efficiency of over 13%, which is comparable to that of the device with a TiO2 compact layer. The different wettability of the perovskite precursor solution on the surface of FTO and TiO2 possesses a significant effect on realizing efficient mesoscopic perovskite solar cell. This result shows a promising future in printable solar cells by further simplifying the fabrication process and lowering the preparation costs. PMID- 27682455 TI - Novel Swelling-Resistant Sodium Alginate Membrane Branching Modified by Glycogen for Highly Aqueous Ethanol Solution Pervaporation. AB - A novel carbohydrate chain cross-linking method of sodium alginate (SA) is proposed in which glycogen with the branched-chain structure is utilized to cross link with SA matrix by the bridging of glutaraldehyde (GA). The active layer of SA composite ceramic membrane modified by glycogen and GA for pervaporation (PV) demonstrates great advantages. The branched structure increases the chain density of the active layer, which compresses the free volume between the carbohydrate chains of SA. Large amounts of hydroxyl groups are consumed during the reaction with GA, which reduces the hydrogen bond formation between water molecules and the polysaccharide matrix. The two factors benefit the active layer with great improvement in swelling resistance, promoting the potential of the active layer for the dehydration of an ethanol-water solution containing high water content. Meanwhile, the modified active layer is loaded on the rigid alpha-Al2O3 ceramic membrane by dip-coating method with the enhancement of anti-deformation and controllable thickness of the active layer. Characterization techniques such as SEM, AFM, XRD, FTIR, XPS, and water contact angle are utilized to observe the composite structure and surface morphology of the composite membrane, to probe the free volume variation, and to determine the chemical composition and hydrophilicity difference of the active layer caused by the different glycogen additive amounts. The membrane containing 3% glycogen in the selective layer demonstrates the flux at 1250 g m-2 h-1 coupled with the separation factor of 187 in the 25 wt % water content feed solution at the operating temperature of 75 degrees C, reflecting superior pervaporation processing capacity compared with the general organic PV membranes in the same condition. PMID- 27682456 TI - First report of Setaria tundra in roe deer (Capreolus capreolus) from the Iberian Peninsula inferred from molecular data: epidemiological implications. AB - BACKGROUND: Filarioid nematode parasites are major health hazards with important medical, veterinary and economic implications. Recently, they have been considered as indicators of climate change. FINDINGS: In this paper, we report the first record of Setaria tundra in roe deer from the Iberian Peninsula. Adult S. tundra were collected from the peritoneal cavity during the post-mortem examination of a 2 year-old male roe deer, which belonged to a private fenced estate in La Alcarria (Guadalajara, Spain). Since 2012, the area has suffered a high roe deer decline rate (75 %), for unknown reasons. Aiming to support the morphological identification and to determine the phylogenetic position of S. tundra recovered from the roe deer, a fragment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene from the two morphologically identified parasites was amplified, sequenced and compared with corresponding sequences of other filarioid nematode species. Phylogenetic analyses revealed that the isolate of S. tundra recovered was basal to all other formely reported Setaria tundra sequences. The presence of all other haplotypes in Northern Europe may be indicative of a South to North outbreak in Europe. CONCLUSIONS: This is the first report of S. tundra in roe deer from the Iberian Peninsula, with interesting phylogenetic results, which may have further implications in the epidemiological and genetic studies of these filarioid parasites. More studies are needed to explore the reasons and dynamics behind the rapid host/geographic expansion of the filarioid parasites in Europe. PMID- 27682457 TI - S-Trifluoromethyl Sulfoximine as a Directing Group in Ortho-Lithiation Reaction toward Structural Complexity. AB - The first use of the NH S-trifluoromethyl sulfoximine as an ortho directing group is described for the functionalization of the aryl group bonded to the sulfur atom. Various electrophiles (halogen, carbon, oxygen, sulfur, boron, etc.) are introduced on the aromatic ring. Cyclic S-trifluoromethyl sulfoximines are synthesized either with properly chosen electrophiles or by structural adjustment of o-azido sulfoximines. Fluorinated analogues of prazosin are also prepared. PMID- 27682458 TI - Good Intention Is Not Enough: Intentional Action to Address Health Disparities in Breastfeeding. PMID- 27682460 TI - Eighth Annual Summit on Breastfeeding Agenda. PMID- 27682459 TI - Reaching the Global Target to Increase Exclusive Breastfeeding: How Much Will It Cost and How Can We Pay for It? AB - There is an urgent need for global action to increase the rates of exclusive breastfeeding. In 2012, the World Health Assembly (WHA) set a global target to increase the rate of exclusive breastfeeding in the first 6 months up to at least 50% by 2025. However, current investment levels are insufficient to drive the kind of progress that is needed to meet the target. Reaching the global nutrition target of increasing exclusive breastfeeding to 50% will require an average annual investment of $570 million over 10 years in addition to what is currently being spent. This investment is projected to result in an additional 105 million children being exclusively breastfed and at least 520,000 child deaths prevented over the next 10 years. This analysis was part of an investment framework developed by the World Bank, Results for Development Institute, and 1,000 Days to provide policy makers with a roadmap for how to reach four of the six WHA global nutrition targets: decreasing childhood stunting, decreasing childhood wasting, decreasing rates of anemia in women of reproductive age, and increasing exclusive breastfeeding in the first 6 months. PMID- 27682461 TI - Eighth Annual Summit on Breastfeeding Participants. PMID- 27682462 TI - Polymorphisms in Toll-like receptor 3 are associated with asthma-related phenotypes in the Chinese Han patients. AB - Toll-like receptor (TLR) 3 mediates antivirus immunity and is involved in asthma exacerbation and development. However, the genetic association between TLR3 and asthma remains unclear. This study aimed to evaluate the effects of polymorphisms within TLR3 on asthma risk and asthma-related phenotypes in the Chinese Han population. A total number of 462 unrelated adult patients with asthma and 398 healthy volunteers were enrolled in this study. The genotypes of tagging single nucleotide polymorphisms (SNPs) in TLR3 gene were determined using multiplex SNaPshot SNP genotyping assays. Case-control and case-only studies were used to assess any links with asthma and asthma-related phenotypes. The results showed that the genetic variants in TLR3 were associated with asthma-related phenotypes, including eosinophil counts, serum immunoglobulin E levels and lung function. However, there was no obvious association between the TLR3 SNPs and asthma susceptibility or asthma severity. TLR3 polymorphisms may play a considerable role in the pathogenesis of asthma. It will help in better understanding the pathogenesis of asthma and development of more effective strategies for the prevention, prediction and treatment of asthma. PMID- 27682463 TI - Towards a Definition of "Self-Neglect" in Psychiatric Patients: Descriptions of a Case Series. AB - Self-neglect, although frequently studied in geriatric populations, has received only limited attention in psychiatric populations. To address this gap, we utilize a behavioral framework to present a set of case examples in order to illustrate the complex relationship between self-neglect behaviors and conditions and various psychiatric illness. Cases are discussed with respect to ascending severity of presentations of self-neglect in adult non-geriatric inpatient psychiatric populations. Self-neglect is conceptualized as a range of behaviors, as well as an overall condition that affects an individual's functioning in several major domains. The concept of self-neglect in non-geriatric psychiatric patients warrants additional study, including development of a formal definition, as well as evaluation of its associated manifestations and implications for treatment and prognosis. PMID- 27682464 TI - Uncovering the essential links in online commercial networks. AB - Recommender systems are designed to effectively support individuals' decision making process on various web sites. It can be naturally represented by a user object bipartite network, where a link indicates that a user has collected an object. Recently, research on the information backbone has attracted researchers' interests, which is a sub-network with fewer nodes and links but carrying most of the relevant information. With the backbone, a system can generate satisfactory recommenda- tions while saving much computing resource. In this paper, we propose an enhanced topology-aware method to extract the information backbone in the bipartite network mainly based on the information of neighboring users and objects. Our backbone extraction method enables the recommender systems achieve more than 90% of the accuracy of the top-L recommendation, however, consuming only 20% links. The experimental results show that our method outperforms the alternative backbone extraction methods. Moreover, the structure of the information backbone is studied in detail. Finally, we highlight that the information backbone is one of the most important properties of the bipartite network, with which one can significantly improve the efficiency of the recommender system. PMID- 27682465 TI - Theoretical Insight into the Mechanisms and Regioselectivity of [4 + 3] and [4 + 1] Annulations of Enals with Azoalkenes Catalyzed by N-Heterocyclic Carbenes. AB - The reaction mechanisms on the NHC-catalyzed [4 + 3] and [4 + 1] annulations of enals with azoalkenes have been theoretically investigated with the aid of the density functional theory calculations. It is found that the additives play an important role in promoting proton transfer and dehydration. The impacts of catalysts (NHC-A and NHC-B) and substituent groups on the regioselectivity were rationalized. The origin of the regioselectivity involved in these reactions was probed by performing distortion-interaction analysis. For reaction A with NHC-A as the catalyst and Boc group as the substituent, the regioselectivity is predicted to be determined by the interaction energy of 3 with R2' in TS3A versus TS8A. For reaction B with NHC-B as the catalyst and Boc group as the substituent, the unstable boat-type conformation versus the stable chair-type conformation involved in the NHC-B moiety accounts for the regioselectivity. In reaction C with NHC-A as the catalyst and Ts group as the substituent, distortion energies of 3 and R2' in TS3C versus TS6C are found to be the major reason delivering regioselectivity even higher than that of reaction A. PMID- 27682466 TI - Developing strengths-based recovery systems through community connections. PMID- 27682467 TI - Porcine sperm vitrification I: cryoloops method. AB - The aims of this study were to evaluate porcine sperm vitrification in cryoloops, with and without two different cryoprotectants and assess two warming procedures. Extended (n = 3; r = 4) and raw (n = 5; r = 2) semen was diluted in media without and with cryoprotectants (4% dimethylformamide and 4% glycerol) to a final concentration of 20 * 106 spermatozoa ml-1 and vitrified using the cryoloops method. Two warming procedures were evaluated: rapid method (30 s at 37 degrees C) and an ultra-rapid method (7 s at 75 degrees C, followed by 30 s at 37 degrees C). Total motility (phase contrast), sperm viability (6-carboxifluorescein diacetate and propidium iodide stain), membrane function (hypo-osmotic swelling test), acrosome integrity (phase contrast), chromatin condensation (toluidine blue stain) and chromatin susceptibility to acid denaturation (acridine orange stain) were evaluated before and after vitrification and analysed using Friedman's test. In all media, the only seminal parameters that were maintained after vitrification were chromatin condensation and integrity. Vitrification of porcine spermatozoon using cryoloops, both in the presence or absence of cryoprotectants and independent of the warming procedure used, permits conservation of sperm chromatin condensation and integrity. It would be interesting to further verify this by producing porcine embryos using vitrified spermatozoon with intracytoplasmic sperm injection. PMID- 27682468 TI - Botryosphaeria dothidea: a latent pathogen of global importance to woody plant health. AB - : Botryosphaeria dothidea is the type species of Botryosphaeria (Botryosphaeriaceae, Botryosphaeriales). Fungi residing in this order are amongst the most widespread and important canker and dieback pathogens of trees worldwide, with B. dothidea one of the most common species on a large number of hosts. Its taxonomic circumscription has undergone substantial change in the past decade, making it difficult to interpret the large volume of literature linked to the name B. dothidea. This pathogen profile synthesizes the current understanding of B. dothidea pertaining to its distribution, host associations and role as a pathogen in managed and natural woody environments. The prolonged latent infection or endophytic phase is of particular importance, as it implies that the fungus can easily pass undetected by quarantine systems in traded living plants, fruits and other plant parts. Infections typically become obvious only under conditions of host stress, when disease symptoms develop. This study also considers the knowledge emerging from the recently sequenced B. dothidea genome, elucidating previously unknown aspects of the species, including mating and host infection strategies. Despite more than 150 years of research on B. dothidea, there is clearly much to be learned regarding this global tree pathogen. This is increasingly important given the stresses imposed on various woody hosts as a result of climate change. TAXONOMY: Botryosphaeria dothidea (Moug. ex Fr) Ces. & De Not, 1863. Kingdom Fungi, Phylum Ascomycota, Class Dothideomycetes, Order Botryosphaeriales, Family Botryosphaeriaceae, Genus Botryosphaeria, Species dothidea. HOST RANGE: Confirmed on more than 24 host genera, including woody plants, such as Acacia (= Vachellia), Eucalyptus, Vitis and Pistachio. DISEASE SYMPTOMS: Associated with twig, branch and stem cankers, tip and branch dieback, fruit rot, blue stain and plant death. USEFUL WEBSITES: The Botryosphaeria site for detailed morphological descriptions (http://www.crem.fct.unl.pt/botryosphaeria_site/); Systematic Mycology and Microbiology Laboratory Fungal Database for all literature and associated hosts (https://nt.ars-grin.gov/fungaldatabases/); TreeBASE link for the combined ITS and TEF-1alpha tree (http://purl.org/phylo/treebase/phylows/study/TB2:S18906); DOE Joint Genome Institute, JGI Mycocosm for the Botryosphaeria dothidea genome (http://genome.jgi.doe.gov/Botdo1_1/Botdo1_1.home.html). PMID- 27682469 TI - Predictors of mortality in pediatric urban firearm injuries. AB - BACKGROUND: Although firearms account for less than 5 % of all pediatric injuries, they have the highest associated case fatality rate. METHODS: The registry at a Level-1 trauma center was used to identify firearm injuries (<18 years of age) from 1991 to 2011. Descriptive statistics and risk-adjusted multivariate analyses (MVA) were performed. RESULTS: Overall, 1085 patients were identified. Immediate operations were performed in 33 % (n = 358) of patients with most having abdominal surgery (n = 214). Survival was 86 %, but higher for African Americans (OR = 1.92) than for Hispanics (p = 0.006). African Americans were more likely to sustain extremity (OR = 2.26) and less head (OR = 0.36) injuries than Hispanics (p < 0.001). Analysis by injury location showed that head (OR = 14.1) had the highest associated mortality. Other significant predictors included multiple major injury (defined by Abbreviated Injury Scale) with central nervous system involvement (OR = 7.30) and single injuries to the chest (OR = 2.68). These findings were compared to abdominal injuries as the baseline (p < 0.02). MVA demonstrated that Caucasian children had higher mortality (OR = 6.12) vs. Hispanics (p = 0.031). Children admitted with initial pH <= 7.15 (OR = 14.8), initial hematocrit <=30 (OR = 3.24), or Injury Severity Score (ISS) > 15 (OR = 1.08) had higher mortality rates (p < 0.05). CONCLUSION: Independent significant indicators of mortality include low initial pH or hematocrit, Caucasian race, high ISS, and those who sustain head injuries. PMID- 27682470 TI - Facile Synthesis of Black Phosphorus: an Efficient Electrocatalyst for the Oxygen Evolving Reaction. AB - Black phosphorus (BP) as a new 2D material has attracted extensive attention because of its unique electronic, optical, and structural properties. However, the difficulties associated with BP synthesis severely hinder the further development of BP for any potential applications. On the other hand, searching for other potential applications of BP is also a big challenge. A facile strategy was developed for preparation of BP supported on Ti foil (BP-Ti) in a thin-film form. Surprisingly, the as-prepared BP shows advanced electrocatalytic activity for the oxygen evolution reaction (OER). To improve the OER activity of the electrocatalyst, BP was grown on a carbon nanotube network (BP-CNT), showing even better activity. The results demonstrate that BP can be prepared by a facile method and may be applied as an electrocatalyst. PMID- 27682471 TI - Infraorbital nerve transposition to expand the endoscopic transnasal maxillectomy. AB - BACKGROUND: The infraorbital nerve (ION) is a terminal branch of the maxillary nerve (V2) providing sensory innervation to the malar skin. It is sometimes necessary to sacrifice the ION and its branches to obtain adequate maxillary sinus exposure for radical resection of sinonasal tumors. Consequently, patients suffer temporary or permanent paresthesia, hypoestesthia, and neuralgia of the face. We describe an innovative technique used for preservation of the ION while removing the anterior, superior, and lateral walls of the maxillary sinus through a medial endoscopic transnasal maxillectomy. METHODS: All patients who underwent transnasal endoscopic maxillectomy with ION transposition in our institute were retrospectively reviewed. RESULTS: Two patients were identified who had been treated for sinonasal cancers using this approach. No major complications were observed. Transient loss of ION function was observed with complete recovery of skin sensory perception within 6 months of surgery. One patient referred to a mild permanent anesthesia of the upper incisors. No diplopia or enophthalmos were encountered in any of the patients. CONCLUSION: The ION transposition is useful for selected cases of benign and malignant sinonasal tumors that do not infiltrate the ION itself but involve the surrounding portion of the maxillary sinus. Anatomic preservation of the ION seems to be beneficial to the postoperative quality of life of such patients. PMID- 27682472 TI - Immunity against influenza A(H1N1) infections is determined by age at the time of initial strain circulation. AB - We explored age-dependent patterns in haemagglutination inhibition (HI) titre to seasonal [1956 A(H1N1), 1977 A(H1N1), 2007 A(H1N1)] and pandemic [A(H1N1)pdm09] influenza strains using serological data collected from an adult French influenza cohort. Subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. We explored age-related differences between strain specific HI titres using 1053 serological samples collected over the study period from 398 unvaccinated subjects. HI titres against the tested seasonal and pandemic strains were determined using the HI technique. Geometric mean titres (GMTs) were estimated using regression models for interval-censored data. Generalized additive mixed models were fit to log-transformed HI estimates to study the relationship between HI titre and age (age at inclusion and/or age at initial strain circulation). GMT against one strain was consistently highest in the birth cohort exposed to that strain during childhood, with peak titres observed in subjects aged 7-8 years at the time of initial strain circulation. Our results complete previous findings on influenza A(H3N2) strains and identify a strain-dependent relationship between HI titre and age at initial strain circulation. PMID- 27682473 TI - Intergenerational solidarity: the paradox of reciprocity imbalance in ageing welfare states. AB - In this article a new theoretical framework is applied to a research field that is somewhat fragmented, namely that of intergenerational solidarity in ageing welfare states. Inspired by utilitarian considerations many scholars tend to problematize the lack of reciprocity characterizing intergenerational exchanges. As some generations are longer old and more numerous they may receive excessive state-administered support of the younger generations, especially in a democratic setting. However, in reality there is limited empirical evidence of intergenerational conflict and theoretical explanations of this paradox are rare. An integrated and dynamical approach that incorporates Durkheim's solidarity theory, Honneth's intersubjective recognition theory, and the current work on reciprocal exchange is necessary in order to understand the survival of intergenerational solidarity in ageing welfare states. According to this model reciprocal recognition leading to the empathization of exchanges is the driving force of intergenerational solidarity in a prefigurative and democratized culture where the status of the young has risen dramatically. Hence, we come to the paradoxical conclusion that attempts to preserve intergenerational solidarity by openly denouncing excessive transfers and trying to bypass them institutionally sometimes might be counterproductive because they may erode their empathic underpinnings. PMID- 27682475 TI - Corrigendum. PMID- 27682477 TI - DISCUSSION: PRACTICE-BASED EVALUATION AS A RESPONSE TO ADRESS INTERVENTION COMPLEXITY. AB - The aim of this special issue of the Canadian Journal of Program Evaluation was to present an overview of current practices in the field of evaluation of complex interventions. Seasoned evaluators described their approaches to these types of evaluation in the healthcare context. Building upon their contributions, this synthesis offers a cross-sectional reading of their experiences, highlighting the common and divergent features of their approaches as well as their most pressing concerns and interests. PMID- 27682476 TI - Caring for Older Adults with the Human Immunodeficiency Virus. AB - Increasing proportions of older adults are living with the human immunodeficiency virus (HIV). It is estimated that more than 50% of individuals with HIV in the United States are aged 50 and older. Part of this group consists of individuals who have aged with chronic HIV infection, but a large proportion also results from new HIV diagnosis, with approximately 17% of new HIV diagnoses in 2013 occurring in individuals aged 50 and older. Although many of the recommendations on management of HIV infection are not age-specific, individuals with HIV aged 50 and older differ from their younger counterparts in many aspects, including immune response to antiretroviral therapy, multimorbidity, antiretroviral toxicities, and diagnostic considerations. This article outline these differences, offers a strategy on how to care for this unique population, and provides special considerations for problem-based management of individuals with HIV aged 50 and older. PMID- 27682474 TI - Sevoflurane-Induced Endoplasmic Reticulum Stress Contributes to Neuroapoptosis and BACE-1 Expression in the Developing Brain: The Role of eIF2alpha. AB - Neonatal exposure to volatile anesthetics causes apoptotic neurodegeneration in the developing brain, possibly leading to neurocognitive deficits in adulthood. Endoplasmic reticulum (ER) stress might be associated with sevoflurane (sevo) induced neuroapoptosis. However, the signaling pathway regulating sevo-induced neuroapoptosis is not understood. We investigated the effects of neonatal sevo exposure on ER signaling pathway activation. Seven-day-old mouse pups were divided into control (C) and sevo (S; 3 % sevo exposure, 6 h) groups. ER stress marker [protein kinase RNA-like ER kinase (PERK), eukaryotic translation initiation factor 2alpha (eIF2alpha), activating transcription factor 4 (ATF4), CHOP, and caspase-12] levels were determined by western blotting. To understand the role of eIF2alpha in sevo-induced ER stress and caspase-3 activation, pups were pretreated with an eIF2alpha dephosphorylation inhibitor, salubrinal, and a potent and selective inhibitor of PERK, GSK2656157, before sevo exposure, and the effects on ER stress signaling and neuroapoptosis were examined. We investigated whether neonatal exposure to sevo increased beta-site APP-cleaving enzyme 1 (BACE 1) expression. Neonatal sevo exposure elevated caspase-3 activation. ER stress signaling was activated, along with increased PERK and eIF2alpha phosphorylation, and upregulation of proapoptotic proteins (ATF4 and CHOP) in the cerebral cortex of the developing brain. Pretreatment with salubrinal augmented sevo-induced eIF2alpha phosphorylation, which inhibited ER stress-mediated ATF4 and caspase-3 activation. Inhibition of PERK phosphorylation due to GSK2656157 pretreatment reduced the sevo-induced increase in eIF2alpha phosphorylation. Sevo increased BACE-1 expression, which was attenuated by GSK2656157 and salubrinal pretreatment. Our data suggested that neonatal sevo exposure-induced neuroapoptosis is mediated via the PERK-eIF2alpha-ATF4-CHOP axis of the ER stress signaling pathway. Modulation of eIF2alpha phosphorylation may play a key role in sevo-induced neurotoxicity in the developing brain. PMID- 27682479 TI - [Promoting the innovation and development of occupational health work with joint efforts]. PMID- 27682478 TI - Differences in vector-genome processing and illegitimate integration of non integrating lentiviral vectors. AB - A variety of mutations in lentiviral vector expression systems have been shown to generate a non-integrating phenotype. We studied a novel 12 base-pair U3-long terminal repeats (LTR) integrase (IN) attachment site deletion (U3-LTR att site) mutant and found similar physical titers to the previously reported IN catalytic core mutant IN/D116N. Both mutations led to a greater than two log reduction in vector integration; with IN/D116N providing lower illegitimate integration frequency, whereas the U3-LTR att site mutant provided a higher level of transgene expression. The improved expression of the U3-LTR att site mutant could not be explained solely based on an observed modest increase in integration frequency. In evaluating processing, we noted significant differences in unintegrated vector forms, with the U3-LTR att site mutant leading to a predominance of 1-LTR circles. The mutations also differed in the manner of illegitimate integration. The U3-LTR att site mutant vector demonstrated IN mediated integration at the intact U5-LTR att site and non-IN-mediated integration at the mutated U3-LTR att site. Finally, we combined a variety of mutations and modifications and assessed transgene expression and integration frequency to show that combining modifications can improve the potential clinical utility of non-integrating lentiviral vectors. PMID- 27682480 TI - [The role of transforming growth factor-beta1/connective tissue growth factor signaling pathway in paraquat-induced pulmonary fibrosis]. AB - Objective: To investigate the effects of Paraquat on human embryonic lung fibroblasts (MRC5) and explore the role of transforming growth factor beta1/connective tissue growth factor signaling pathway in paraquat-induced pulmonary fibrosis. Methods: MRC5 cells were cultured with different concentration of PQ (0, 12.5, 25, 50, 100, 200, 400 MUmol/L) for 24 h. The viability of cells was measured by MTT. The protein level of TGF-beta1 were analyzed by ELISA after PQ treatment (0, 25, 50, 100 MUmol/L) . To examine whether TGF-beta1/CTGF signaling pathway was involved in paraquat-induced cytotoxicity, cells was divided into 6 groups: (1) control; (2) 25 MUmol/L PQ group; (3) 50 MUmol/L PQ group; (4) 100 MUmol/L PQ group; (5) TGF-beta1 positive control group (50 MUmol/L rhTGF-beta1) ; (6) stimulate group (100 MUmol/L PQ+50 MUmol/L TGF-beta1) . The protein levels of p-Smad2, p-Smad3 and CTGF were assayed by western blot. The mRNA level of CTGF was assayed by real time RT-PCR. Results: MTT showed that cell viability decreased with increasing PQ concentration (P<0.05) . The protein expression of TGF-beta1 treated with PQ (25, 50, 100 MUmol/L) significantly increased compared with control in a dose-independent manner (P<0.05) . Exposure to PQ (25, 50, 100 MUmol/L) induced increase of protein levels of p-Smad2 and p-Smad3. Noteworthy, the expression of p-Smad2 and p-Smad3 were dramatically increased following PQ plus TGF-beta1 stimulation (P<0.05) . Exposure to PQ (50, 100MUmol/L) induced increase of CTGF protein expression and similar greatly increase following PQ plus TGF-beta1 stimulation (P<0.05) . Real time RT-PCR showed CTGF mRNA in all groups also significantly up regulated compared with control (P<0.05) . Conclusion: TGF-beta1 regulates the expression of target gene CTGF to exhibit its pro-fibrogenic effects by activating TGF-beta1/Smad signaling pathway in PQ-induced pulmonary fibrosis. PMID- 27682481 TI - [The role of BDNF pathway in lambda-cyhalothrin disrupting the promotion of 17beta-Estradiol on Post-synaptic Density 95 protein expression in HT22 cell]. AB - Objective: To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons. Methods: HT22 cell line were used to, treating with lambda-cyhalothrin (LCT, 50 MUmol/L) , 17beta-Estradiol (E2, 10 nmol/L) , LCT (50 MUmol/L) +TrkB FC (20 MUg/ml) , E2 (10 nmol/L) +TrkB FC (20 MUg/ml) , LCT (50 MUmol/L) +ICI182 780 (1 MUmol/L) , E2 (10 nmol/L) + ICI182 780 (1 MUmol/L) , LCT (50 MUmol/L) +E2 (10 nmol/L) for 24 h. MTT kit was used to detect cell viability. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell. Results: Campared to Sham, LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF (P<0.05) , campared to LCT, LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF (P<0.05) , campared to E2, E2+TrkB FC could reduce the expression of PSD95 and E2+ICI could reduce the expression of BDNF (P<0.05) , campared to E2, LCT+ E2 could reduce the expression of PSD95 and BDNF (P<0.05) . Conclusion: BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells. Although LCT alone has a similar effect on E2. LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway. PMID- 27682482 TI - [Application of benchmark dose on renal injury in people chronically exposed to lead]. AB - Objective: To screen sensitive indicators of renal injury in lead workers using benchmark dose method. Methods: Of the 486 subjects,116 did not occupationally contact to lead as a control. The blood lead was considered as exposure biomarker, while Ubeta2-MG and UNAG as effect biomarkers for renal injury. The BMD and BMDL of blood lead were estimated at the 10% benchmark response using BMDS Version 2.6. Results: There was statistical rise in blood lead between the lead group and control group (P<0.05) ; and the blood lead level was divided into four groups by quarterback spacing method, among which UNAG was statistically different (P<0.05) . There was an increased prevalence of abnormal rates of Ubeta2-MG and UNAG with increasing blood lead concentration (P<0.05) , after trend chi-square test. BMD and BMDL of UNAG and Ubeta2-MG were 602.784/431.838 MUg/L and 130.398/100.981 MUg/L caculated by Log-Probit model, respectively. Conclusions: Occupational lead exposure may cause kidney damage, and UNAG could be as a more sensitive marker for monitoring early renal injury than Ubeta2-MG. PMID- 27682483 TI - [Mental health research for new nurse during the standardized training period]. AB - Objective: To explore the mental health status for new nurse during the standardization training period and provide scientific basis for managers to formulate corresponding measures. Methods: Using eysenck personality questionnaire (EPQ) and symptom self-assessment scale (SCL-90) , understanding social support scale (PSSS) , trait coping style questionnaire (TCSQ) and other standardized psychological assessment tools and self designed general situation questionnaire, 141 nurses in our hospital before rotary department and 1 year later accepted the questionnaire survey while the control group accepted the same questionnaire. Results: Compared with before rotary department and the control group, the forced, anxiety and interpersonal sensitivity factor increased significantly in SCL-90 for rotary nurse and the differences were significant statistical significance (P<0.05) ; Pearson correlation analysis showed rotary nurse SCL-90 forcing factor scores and EPQ-E dimension scores, TCSQ negative coping scores were positively correlated (P<0.05; r1=0.537; r2=0.407; r3=0.701) , and were negatively correlated with EPQ-E dimension scores, PSSS scores and TCSQ active responding score (P<0.05; r1=-0.621; r2=-0.671; r3=-0.312) ; Anxiety was positively correlated with EPQ-N, PSSS scores and TCSQ negative responding score (P<0.05; r1=0.607; r2=0.409; r3=0.764) , was negatively correlated with EPQ-E dimension scores, PSSS scores and TCSQ positive responding score (P<0.05; r1= 0.569; r2=-0.723; r3= -0.418) ; Interpersonal sensitivity factor score was positively correlated with EPQ-N, P dimension scores and TCSQ negative coping scores (P<0.05; r1=0.611; r2=0.687; r3=0.773) , was negatively correlated with EPQ-E dimension scores, PSSS scores and TCSQ active responding score (P<0.05; r1= 0.506; r2=-0.693; r3=-0.307) . Conclusion: Rotary nurse mental health status was significantly lower than non-rotary nurse.Insufficient social support, negative coping style and instability personality characteristics are the main risk factors to affect the rotation nurses mental health. PMID- 27682484 TI - [Somewhere in tertiary hospital clinical laboratory in pursuance of personnel sharp injury incidence status investigation and relative factor analysis]. AB - Objective: Investigation in tertiary hospital clinical laboratory in pursuance of the current state of the sharp injury incidence and influencing factors, analyze the causes and discuss the control strategy. Methods: Application of cross sectional survey method, according to the unified investigation questionnaire investigation, with chi-square test and the multi-factor Logistic regression analysis methods to analyze research data. Results: The work environment exit contact with injection needles, glass and other sharps, contact with noise, contact with chemicals, contact the patient's blood and other biological specimens, high-risk groups, the patient and family to negative emotions, by patients and their families complain or abuse related influencing factors. In the organization and management factors, in order to work strength is insufficient for the most dissatisfied, protective equipment, medical staff personal cognitive factors of occupational exposure, failing to abide by the medical care standard operation and high incidence after exposure to failed to report. Somewhere in tertiary hospital clinical laboratory in pursuance of the incidence of sharps injuries associated with five factors: different jobs, working strength, protective equipment perfect or not, sharp instrument use and disposal of medical wastes. Conclusion: Tertiary hospital clinical laboratory in pursuance of the incidence of sharp injury related to many factors, Hospitals should formulate corresponding rules and regulations, improve the working environment, the standard safety operation, reduced the incidence of sharps injuries. PMID- 27682485 TI - [An analysis of the clinical and epidemiological characteristics of acute poisoning patients in a general hospital]. AB - Objective: To analyze the clinical and epidemiological characteristics of acute poisoning patients in a general hospital, then to provide a reference for the prevention and treatment of acute poisoning in the future. Methods: A retrospective analysis was made on the clinical data of 660 patients with acute poisoning admitted in emergency medical center of the First Affiliated Hospital of Wenzhou Medical University from July 2009 to May 2015. Results: More men than women in 660 cases with acute poisoning(the ratio of male to female was 1.36?1) ; >=30 years old was the high incidence age (78.79%) ; The top occupation was farmers (39.70%) ; Most were life poisoning (88.18%) , suicide was the main reason (62.42%) especially happened in women, and the main cause of suicide was family conflicts; Toxic species dominated by pesticide (67.58%) , most were severe poisoning (81.82%) ; The top two pesticide poisoning were organic phosphorus and paraquat, and the proportion of blood purification in paraquat was significantly higher (chi2=105.21, P=0.00) ; There were 212 cases with organ dysfunction, main were pesticide poisoning patients, and the proportionof organ dysfunction in paraquat was significantly higher than the rest allpesticide poisoning (chi2=45.09, P=0.00) ; The general fatal rate of acute poisoning was 2.27%, and the proportion in paraquat poisoning was .higher than the rest pesticide poisoning who were death and give up when discharged (chi2=56.83, P=0.00) . Conclusion: The focus of acute poisoning in the general hospital is still pesticide (especially organic phosphorus and paraquat) , and most were severe poisoning. PMID- 27682486 TI - [Research on the therapeutic effects of drugs on patients with pneumoconiosis in China]. AB - Objective: To review the clinical research on the main drugs which are used to treat pneumoconiosis in China, evaluate and analyze the efficacy, and give the suggestions on the study of pneumoconiosis treatment. Methods: The data of researches on the therapeutic effects of eight main drugs on patients with pneumoconiosis in China were retrieved from CNKI and Wanfang database before Jan. 1, 2016 including polyvinylpyridine, tetrandrine, piperaquine phosphate, hydroxypiperaquine phosphate, aluminium citrate, Xinin, Xifeining and N-acetyl cysteine (NAC) after consulting the related project files on the clinical treatment on the patients with pneumoconiosis, and a systematic analysis was made on the random control test (RCT) which conformed to the quality criteria in terms of five indices such as the improvement rate of respiratory system symptoms such as cough, expectoration, chest pain and dyspnea, the decrease of the respiratory system infection rate, the changes in FEV1.0% (forced expired volume in one second to forced vital capacity ratio) (DeltaFEV1.0%) , index of stability and improvement rate of chest X-ray, and adverse reactions as well as the summary of descriptive efficacy. Results: Nine RCTs in the 15 papers were included; 2 097 patients with pneumoconiosis were included with 1215 in the treatment group and 882 in the control group. The medication modes were divided into four categories, monotherapy (such as polyvinylpyridine, hydroxypiperaquine phosphate, Xifeining and Xinin) , combination of tetrandrine with other drugs, hydroxypiperaquine phosphate and aluminium citrate, and lung lavage (added medications) ; the analysis indicated that the patients in the treatment group were obviously superior to those in the control group in terms of the improvement rate of respiratory system symptoms, the decrease rate of the respiratory tract infection, DeltaFEV1.0%, the improvement rate of shadows as indicated in the X ray chest film and the index of stability (P<0.01) ; after the mean values of the control group were deducted, the improvement rate of symptoms of the respiratory system within the treatment period of the patients with pneumoconiosis increased by 34.6% (95% CI 32.9%, 36.3%) in average, the mean value of the decrease in the respiratory tract infection rate was 26.0% (95% CI 24.0%, 28.0%) , the mean value of DeltaFEV1.0% was 4.08 (95% CI 3.56, 4.60) , the improvement rate in X-ray chest film increased by 8.80% (95% CI 8.55%, 9.05%) in average, and the index of stability in the X-ray chest film increased by 10.6% (95% CI 9.18%, 12.0%) ; one way analysis of variance indicated the presence of statistical difference in terms of efficacy of four categories of medication modes (Fthe improvement rate of symptoms of the respiratory system=482.2, P<0.01; Fthe decrease in the respiratory tract infection rate=72.01, P<0.01; FDeltaFEV1.0%=246.6, P<0.01; Fthe index of stability in the X-ray chest film=212.9, P<0.01; Fthe improvement rate of X-ray chest film=466.6, P<0.01) . Conclusion: Drugs such as polyvinylpyridine, tetrandrine, hydroxypiperaquine phosphate, aluminium citrate, Xinin, Xifeining and NAC have some efficacy in the treatment of pneumoconiosis. It is suggested that, in accordance with the mechanism of pneumosilicosis onset and the action mechanism of drugs and on the basis of the research on the traditional drugs, the latest clinical study results and the management experiences on the idiopathic pulmonary interstitial fibrosis be constantly traced and borrowed to strengthen the research on the drugs which are used to treat the pneumoconiosis and the patient health management. PMID- 27682487 TI - [Health status of dust-exposed workers in a precision casting enterprise]. AB - Objective: To investigate the health status of workers exposed to zircon sand and silica dust in a precision casting enterprise, and to provide a basis for the development of prevention and control measures. Methods: Occupational health examination, questionnaire survey, and field investigation of occupational health were performed for 176 male workers (18 workers in the zirconium dust exposure group, 109 in the non-zirconium dust exposure group, and 49 in the non-dust exposure group) in a precision casting enterprise, and a statistical analysis was performed for the data obtained. Results: Dust and noise were major hazard factors for occupational diseases in this enterprise. The abnormal rate of physical examination was 71.02%. Compared with the non-zirconium dust exposure group, the zirconium dust exposure group had significantly higher detection rates of restrictive ventilatory dysfunction, increased immunoglobulin IgE, increased alanine aminotransferase, and increased alkaline phosphatase (ALP) (P<0.05) ; compared with the non-dust exposure group, the zirconium dust exposure group had a significantly higher detection rate of increased ALP (P<0.05) . Of all workers, 15 were found to have pneumoconiosis-like changes (11 had pneumoconiosis and 4 needed observation) , among whom 4 were in the zirconium dust exposure group (3 had pneumoconiosis and 1 needed observation) and 11 were in the non-zirconium dust exposure group (8 had pneumoconiosis and 3 needed observation) . The detection rate of pneumoconiosis-like changes showed no significant differences between the two groups (20.22% vs 10.09%) . Conclusions: There was a severe dust hazard in this enterprise. Inhalation of dust containing zirconium is associated with respiratory system injury, especially the development of pneumoconiosis, and it may also cause immune dysfunction and liver impairment. PMID- 27682488 TI - [Risk factors for pulmonary fibrosis in patients with paraquat poisoning]. AB - Objective: To investigate the risk factors for pulmonary fibrosis in patients with paraquat (PQ) poisoning. Methods: A total of 120 patients with PQ poisoning who were admitted from January 2012 to December 2014 were enrolled. According to the presence or absence of pulmonary fibrosis, the patients were divided into non pulmonary fibrosis group (67 patients) and pulmonary fibrosis group (53 patients) . The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was obtained on days 1 and 3 of poisoning. Routine blood test results, blood biochemical parameters, and radiological parameters were recorded, and the patients with PQ poisoning were followed up for survival and pulmonary fibrosis. Results: A total of 39 patients with PQ poisoning died, resulting in a mortality rate of 32.5%. There were 53 patients who developed pulmonary interstitial fibrosis, yielding an incidence rate of 44.2%. Compared with the non-pulmonary fibrosis group, the pulmonary fibrosis group had a significantly higher age, a significantly higher dose of PQ, and significantly higher APACHE II scores on days 1 and 3 of poisoning (P<0.01) , as well as significantly higher white blood cell (WBC) count and neutrophil count on day 1, significantly higher levels of urea nitrogen, creatinine, and blood glucose on days 1 and 3, and significantly higher activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01) . The logistic regression analysis showed that the dose of PQ, WBC count and neutrophil count on day 1, APACHE II scores on days 1 and 3 of poisoning, levels of urea nitrogen, creatinine, and blood glucose, and activities of AST and ALT were associated with the development of pulmonary fibrosis in patients with PQ poisoning. Conclusion: Oral dose of PQ, APACHE II scores on days 1 and 3 of poisoning, levels of urea nitrogen, creatinine, and blood glucose, activities of AST and ALT, and WBC count and neutrophil count on day 1 are risk factors for pulmonary fibrosis in patients with paraquat poisoning. PMID- 27682489 TI - [Influencing factors for trauma-induced tibial infection in underground coal mine]. AB - Objective: To investigate the influencing factors for trauma-induced tibial infection in underground coal mine. Methods: A retrospective analysis was performed for the clinical data of 1 090 patients with tibial fracture complicated by bone infection who were injured in underground coal mine and admitted to our hospital from January 1995 to August 2015, including the type of trauma, injured parts, severity, and treatment outcome. The association between risk factors and infection was analyzed. Results: Among the 1 090 patients, 357 had the clinical manifestations of acute and chronic bone infection, 219 had red and swollen legs with heat pain, and 138 experienced skin necrosis, rupture, and discharge of pus. The incidence rates of tibial infection from 1995 to 2001, from 2002 to 2008, and from 2009 to 2015 were 31%, 26.9%, and 20.2%, respectively. The incidence rate of bone infection in the proximal segment of the tibia was significantly higher than that in the middle and distal segments (42.1% vs 18.9%/27.1%, P<0.01) . As for patients with different types of trauma (Gustilo typing) , the patients with type III fracture had a significantly higher incidence rate of bone infection than those with type I/II infection (52.8% vs 21.8%/24.6%, P<0.01) . The incidence rates of bone infection after bone traction, internal fixation with steel plates, fixation with external fixator, and fixation with intramedullary nail were 20.7%, 43.5%, 21.4%, and 26.1%, respectively, suggesting that internal fixation with steel plates had a significantly higher incidence rate of bone infection than other fixation methods (P<0.01) . The multivariate logistic regression analysis showed that the position of tibial fracture and type of fracture were independent risk factors for bone infection. Conclusion: There is a high incidence rate of trauma-induced tibial infection in workers in underground coal mine. The position of tibial fracture and type of fracture are independent risk factors for bone infection. Vacuum sealing drainage and Ilizarov technique can achieve a satisfactory therapeutic effect. PMID- 27682490 TI - [The expression of serum miRNAs in pneumoconiosis complicated with pulmonary tuberculosis patients]. AB - Objective: To inquiry the changes of serum miRNAs expression in pneumoconiosis complicated with pulmonary tuberculosis patients. Methods: The study subjects (all subjects are male) were divided into three groups: Istage pneumoconiosis (38 cases) ,Pneumoconiosis complicated with pulmonary tuberculosis (12 cases) and healthy control (40cases) . The first two groups come from Tianjin worker's sanatorium and healthy control group came from a Hospital Health Screening Center. RT-qPCR was used to detect the expression levels of miR-21, miR-200c, miR 16, miR-204, miR-206, miR-155, let-7g, miR-30b, miR-192, miR-29a in serum. Results: Compared with the healthy control group, the expression levels of miR 204, miR-206, miR-21, miR-16, miR-29a, miR-155, miR-200c in other two groups are different (P<0.05) ; Compared with the Istage pneumoconiosis, the expression levels of miR-155 is significantly higher (P<0.05) and miR-29a is significantly lower (P<0.05) . Conclusion: Compared with the Istage pneumoconiosis, the expression levels of miR-155 and miR-29a are significantly different, suggesting that these two miRNAs may play a important role in the process of pneumoconiosis complicated with pulmonary tuberculosis. PMID- 27682491 TI - [Hospital costs and related influencing factors in patients with acute poisoning]. AB - Objective: To investigate the hospital costs and related influencing factors in patients with acute poisoning. Methods: A retrospective analysis was performed for the general status and hospital costs of 373 patients with acute poisoning who were admitted to The Second Affiliated Hospital of Wenzhou Medical College from January 2009 to March 2015. The questionnaires were completed, the data were entered into Excel forms, and SPSS 18.0 was used to perform statistical analysis. Results: Among the 373 patients, 44.8% committed suicide and 31.1% were poisoned by accidental contact; 42.6% were poisoned by pesticides, and 32.7% were poisoned by drugs. After treatment, 64.1% achieved improvements, whereas 1.3% died. The highest hospital cost reached 62 710.26 RMB, and the lowest was 64.64 RMB (median 4 328 RMB) . The patients with an older age and a longer length of hospital stay tended to have higher hospital costs; the patients who underwent catharsis, mechanical ventilation, and blood purification and were admitted to the intensive care unit had relatively high hospital costs. Conclusion: The patients with acute poisoning have high hospital costs. Poisoning caused by pesticides and drugs should be prevented and treated with priority, so as to reduce the heavy economic burden caused by acute poisoning. PMID- 27682492 TI - [Changes of microRNAs profiling in mesothelial cells exposed to multi-walled carbon nanotubes]. AB - Objective: To explore the cytotoxicities of MWCNT to the mesothelial cells and screen the changes of microRNA profile after exposure to MWCNT. Methods: A LDH method was used to test the cytotoxicities of MWCNT to MeT-5A cell lines. And then the differentially expressed miRNAs between mesothelioma cells and normal mesothelial cells were selected from previous work of research group. Among the significant expression changed miRNAs, 5 were verified by RT-qPCR in mesothelioma cells. The same five ones were further tested in MeT-5A cells exposed to 10 MUg/cm2 MWCNT for 8, 24, 48, 72 h by RT-qPCR. Target genes of 5 miRNAs were predicted using Targetscan and miRanda softwares. David6.7 was used to perform GO enrichment and KEGG pathway analysis of target genes. All the data were analyzed by one-way ANOVA and Dunnett-T test in SPSS17.0. Results: After 24 h exposure to MWCNT, cell proliferation was significantly suppressed at more than 20 MUg/cm2 concentration. Among the differentially expressed miRNAs, 5 were chosen to further vestified, namely hsa-miR-155 (up-regulated) , hsa-miR-30 d-5p, hsa-miR 34c-5p, hsa-miR-28-5p and hsa-miR-324-5p (down-regulated) , which were consistent with the miRNA array results. The 5 miRNAs also had the same expression changes in MeT-5A cells after exposure to 10 MUg/cm2 MWCNT for different time periods. The potential target genes of the 5 miRNAs may be AKAP13, CCND3, Twist and E Cadherin, which mainly involved in TGF-beta signal pathway, small cell lung cancer, etc. Conclusion: MWCNT could induce to MeT-5A cells, and also cause miRNA expression changes. The differential changed miRNAs may involve in cancer related signal pathways. PMID- 27682494 TI - [Clinical features of acute severe ammonia poisoning and its respiratory sequelae]. PMID- 27682493 TI - [Clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in treatment of acute paraquat poisoning]. AB - Objective: To investigate the clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in the treatment of acute paraquat poisoning. Methods: A total of 80 patients with acute paraquat poisoning who were admitted to our hospital were enrolled as study subjects and randomly divided into routine treatment group (38 patients) and traditional Chinese medicine (TCM) group (42 patients) . The patients in the TCM group were given compound monoammonium glycyrrhizinate and dandelion in addition to the treatment in the control group. Serum alanine aminotransferase (ALT) , total bilirubin (TBil) , blood urea nitrogen (BUN) , creatinine (Cr) , and arterial blood lactate (Lac) and partial pressure of oxygen (PaO2) during different time periods on day 3, 7, and 9 of treatment were observed in both groups, and ulceration of oral mucosa, pulmonary fibrosis, multiple organ dysfunction syndrome (MODS) , and mortality were compared between the two groups. Results: On days 3, 7, and 9 of treatment, the routine treatment group had significantly higher serum ALT, TBil, BUN, Cr, and arterial blood Lac than the TCM group. The routine treatment group had significantly lower arterial blood PaO2 than the TCM group, while the TCM group had significantly lower incidence rates of ulceration of oral mucosa, pulmonary fibrosis, and MODS and a significantly lower mortality rate than the routine treatment group (P<0.05) . Conclusion: In the treatment of patients with acute paraquat poisoning, compound monoammonium glycyrrhizinate combined with dandelion can effectively improve organ function, reduce the incidence of pulmonary fibrosis and MODS, improve the healing rate of oral ulcer, improve prognosis, and reduce mortality rate. PMID- 27682495 TI - [Solicosis with one micorscopic polyangitis case complicated]. PMID- 27682496 TI - [Nursing care of 13 cases of thumb reconstruction with acute occupational hand injury]. PMID- 27682497 TI - [A case report of chromate manufacturing workers with lung cancer]. PMID- 27682498 TI - [One case of eyes contact methanol induced toxic eyes disease]. PMID- 27682499 TI - [<>problems encountereal in the application]. PMID- 27682500 TI - [The wle of high mobility group protein B1(HMGB-1) on inflammatony responese and pulmonary fibrosis induced by silica dusty]. PMID- 27682501 TI - [Advances in detection methods for pyrethroid insecticides and their metabolites in human biological samples of human]. PMID- 27682502 TI - [Summary of studies on carcinogenicity of 1-bromopropane]. PMID- 27682503 TI - The Solvent-Exposed C-Terminus of the Cytolysin A Pore-Forming Toxin Directs Pore Formation and Channel Function in Membranes. AB - Pore-forming toxins (PFTs) bind to cell membranes and form nanoscale pores that allow leakage of cellular components, resulting in cell death. The water-soluble, monomeric form of these toxins shows a dramatic conformational change during pore formation, as exemplified by crystal structures of the monomer and functional pore of cytolysin A (ClyA). The solvent-exposed, C-terminal residues of the protein are essential for activity, but the mechanism by which this region regulates pore formation remains unknown. We show here that deletion of the C terminus of ClyA did not alter its ability to bind to the membrane or oligomerize in detergent. However, the truncated toxin lysed erythrocytes poorly, was more susceptible to proteolysis and thermal unfolding, and showed low calcein leakage from small unilamellar vesicles. Using fully atomistic molecular dynamics (MD) simulations, we find that deletion of C-terminal residues from the ClyA monomer significantly altered stability and unfolding trajectories in the transmembrane N terminal helix, a region that is pivotal in maintaining the structural integrity of the helical bundle. MD simulations of pores with or without the C-terminus showed minor differences, implying that if oligomerization could be induced prior to the addition to vesicles, then an active pore could be generated. Via generation of oligomers in a detergent prior to the addition to vesicles, the truncated toxin could induce calcein leakage from vesicles, albeit to a lower extent. Therefore, regions of pore-forming toxins, not directly involved in the pore structure, are not passive players but have important roles in undergoing the transition through intermediary steps leading to successful pore formation in a membrane environment. PMID- 27682504 TI - Optic nerve head slope-based quantitative parameters for identifying open-angle glaucoma on SPECTRALIS OCT images. AB - PURPOSE: To investigate monitoring slope-based features of the optic nerve head (ONH) cup as open-angle glaucoma (OAG) occurs. METHOD: A dataset of 46 retrospective OCT cases was acquired from the SPECTRALIS Heidelberg Engineering OCT device. A set of five parameters, which are based on the ONH cup-incline, are measured on the OAG and normal subjects in the dataset. Then, three new ONH cup shape indices were deduced. The ONH cup-incline parameters and ONH cup-shape indices are analyzed to estimate their clinical value. RESULTS: The statistical difference between measurements on normal and glaucoma eyes was remarkably significant for all of the analyzed parameters and indices (p value < 0.001). CONCLUSIONS: The geometric shape of the ONH cup can be transferred to numerical parameters and indices. The proposed ONH cup-incline parameters and ONH cup-shape indices have shown suggestive clinical value to identify the development of OAG. As OAG appears, the top ONH cup-incline parameters decrease while the bottom ONH cup-incline parameters increase. The ONH cup-shape indices suggest capability to discriminate OAG from normal eyes. PMID- 27682505 TI - Magnetic Circular Dichroism Evidence for an Unusual Electronic Structure of a Tetracarbene-Oxoiron(IV) Complex. AB - In biology, high valent oxo-iron(IV) species have been shown to be pivotal intermediates for functionalization of C-H bonds in the catalytic cycles of a range of O2-activating iron enzymes. This work details an electronic-structure investigation of [FeIV(O)(LNHC)(NCMe)]2+ (LNHC = 3,9,14,20-tetraaza-1,6,12,17 tetraazoniapenta-cyclohexacosane-1(23),4,6(26),10,12(25),15,17(24),21-octaene, complex 1) using helium tagging infrared photodissociation (IRPD), absorption, and magnetic circular dichroism (MCD) spectroscopy, coupled with DFT and highly correlated wave function based multireference calculations. The IRPD spectrum of complex 1 reveals the Fe-O stretching vibration at 832 +/- 3 cm-1. By analyzing the Franck-Condon progression, we can determine the same vibration occurring at 616 +/- 10 cm-1 in the E(dxy -> dxz,yz) excited state. Both values are similar to those measured for [FeIV(O)(TMC)(NCMe)]2+ (TMC = 1,4,8,11-tetramethyl-1,4,8,11 tetraazacyclotetradecane). The low-temperature MCD spectra of complex 1 exhibit three pseudo A-term signals around 12 500, 17 000, and 24 300 cm-1. We can unequivocally assign them to the ligand field transitions of dxy -> dxz,yz, dxz,yz -> dz2, and dxz,yz -> dx2-y2, respectively, through direct calculations of MCD spectra and independent determination of the MCD C-term signs from the corresponding electron donating and accepting orbitals. In comparison with the corresponding transitions observed for [FeIV(O) (SR-TPA)(NCMe)]2+ (SR-TPA = tris(3,5-dimethyl-4-methoxypyridyl-2-methy)amine), the excitations within the (FeO)2+ core of complex 1 have similar transition energies, whereas the excitation energy for dxz,yz -> dx2-y2 is significantly higher (~12 000 cm-1 for [FeIV(O)(SR-TPA)(NCMe)]2+). Our results thus substantiate that the tetracarbene ligand (LNHC) of complex 1 does not significantly affect the bonding in the (FeO)2+ unit but strongly destabilizes the dx2-y2 orbital to eventually lift it above dz2. As a consequence, this unusual electron configuration leads to an unprecedentedly larger quintet-triplet energy separation for complex 1, which largely rules out the possibility that the H atom transfer reaction may take place on the quintet surface and hence quenches two-state reactivity. The resulting mechanistic implications are discussed. PMID- 27682506 TI - Clinical characteristics of canine fibrocartilaginous embolic myelopathy (FCE): a systematic review of 393 cases (1973-2013). AB - Fibrocartilaginous embolic myelopathy (FCE) is common in dogs; however, there is conflicting information in the veterinary literature regarding clinical characteristics and data on recovery in severe cases is sparse. A systematic review of canine FCE was performed to delineate the natural history of this disease. 322 previously reported cases and 71 previously unreported cases were identified for inclusion. Source publications were identified via PubMed central search and by references from review articles. Previously unreported cases were identified via computerised medical records search at two veterinary institutions. FCE was most common in middle-aged large breed dogs (30 per cent); however, the miniature schnauzer was the most frequently reported individual breed and small breeds comprised 24 per cent of all reported cases. The most common neuroanatomical localisation was a T3-L3 myelopathy (33.1 per cent). Prognosis for recovery of ambulation was good to excellent with 85 per cent of cases regaining the ability to walk unassisted, most within 3 weeks. Persistent neurological deficits were common in patients that recovered ambulation (49.1 per cent). When nociception was absent in the affected limbs at initial presentation, rate of recovery was lower (10 per cent); however, this data is likely biased by limited follow-up in more severe cases. Future prospective studies should evaluate prognosis for more severely affected patients. PMID- 27682508 TI - Preparing for the unpredictable: The continuing need for pandemic influenza preparedness. PMID- 27682507 TI - Discovery of a Potent and Selective in Vivo Probe (GNE-272) for the Bromodomains of CBP/EP300. AB - The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0.02 MUM, BRET IC50 = 0.41 MUM, BRD4(1) IC50 = 13 MUM) that retained the best balance of cell potency, selectivity, and in vivo PK. Compound 59 showed a marked antiproliferative effect in hematologic cancer cell lines and modulates MYC expression in vivo that corresponds with antitumor activity in an AML tumor model. PMID- 27682509 TI - Prevalence of serum neutralizing antibodies to adenovirus type 5 (Ad5) and 41 (Ad41) in children is associated with age and sanitary conditions. AB - Neutralizing antibody (NAb) can dampen the immunogenicity of adenovirus (Ad) vector-based vaccine. Vector systems based on human adenovirus type 41 (Ad41) have been constructed and used to develop recombinant vaccines. Here, we attempted to study the seroprevalence of NAbs to Ad5 and Ad41 among children and adults in Qinghai province, China. The positive rates (titer?40) of Ad5 and Ad41 NAb in adults from Xining city were 75.7% and 94.7%, respectively. The moderate/high-positive rates (titer?160) of NAb were quite close between the two viruses in adults (70.4% for Ad5 and 73.5% for Ad41). Age-dependent increase of NAb seroprevalence was observed for both viruses in children. NAb-positive rate of Ad41 reached 50% at 3.3-4.6years of age for children from Chengxi district, Xining city, approximately 1.5years earlier than that of Ad5 did. Interestingly, NAb level was also associated with sanitary conditions among young children. For Ad5, 8-15% children (0.2-3.0years of age) from city or town, where the sanitations were relatively better, had moderate/high-positive NAb, while the same rate was 62% for children from villages. For Ad41, 22% children from city, 47% from town and 88% from villages possessed moderate/high-positive NAb. The possible influence of NAb titer distributions on the application of Ad41-vectored vaccines was discussed in detail. Our results suggested that children from places with poor sanitations should be included for comprehensive Ad NAb seroprevalence studies, and provided insights to the applications of Ad41 vectors. PMID- 27682511 TI - EGS_cbct: Simulation of a fan beam CT and RMI phantom for measured HU verification. AB - INTRODUCTION: A mathematical 3D model of an existing computed tomography (CT) scanner was created and used in the EGSnrc-based BEAMnrc and egs_cbct Monte Carlo codes. Simulated transmission dose profiles of a RMI-465 phantom were analysed to verify Hounsfield numbers against measured data obtained from the CT scanner. METHODS AND MATERIALS: The modelled CT unit is based on the design of a Toshiba Aquilion 16 LB CT scanner. As a first step, BEAMnrc simulated the X-ray tube, filters, and secondary collimation to obtain phase space data of the X-ray beam. A bowtie filter was included to create a more uniform beam intensity and to remove the beam hardening effects. In a second step the Interactive Data Language (IDL) code was used to build an EGSPHANT file that contained the RMI phantom which was used in egs_cbct simulations. After simulation a series of profiles were sampled from the detector model and the Feldkamp-Davis-Kress (FDK) algorithm was used to reconstruct transversal images. The results were tested against measured data obtained from CT scans. RESULTS: The egs_cbct code can be used for the simulation of a fan beam CT unit. The calculated bowtie filter ensured a uniform flux on the detectors. Good correlation between measured and simulated CT numbers was obtained. CONCLUSIONS: In principle, Monte Carlo codes such as egs_cbct can model a fan beam CT unit. After reconstruction, the images contained Hounsfield values comparable to measured data. PMID- 27682512 TI - A Clinical Prediction Algorithm to Stratify Pediatric Musculoskeletal Infection by Severity. AB - OBJECTIVE: There are currently no algorithms for early stratification of pediatric musculoskeletal infection (MSKI) severity that are applicable to all types of tissue involvement. In this study, the authors sought to develop a clinical prediction algorithm that accurately stratifies infection severity based on clinical and laboratory data at presentation to the emergency department. METHODS: An IRB-approved retrospective review was conducted to identify patients aged 0 to 18 who presented to the pediatric emergency department at a tertiary care children's hospital with concern for acute MSKI over a 5-year period (2008 to 2013). Qualifying records were reviewed to obtain clinical and laboratory data and to classify in-hospital outcomes using a 3-tiered severity stratification system. Ordinal regression was used to estimate risk for each outcome. Candidate predictors included age, temperature, respiratory rate, heart rate, C-reactive protein (CRP), and peripheral white blood cell count. We fit fully specified (all predictors) and reduced models (retaining predictors with a P-value <=0.2). Discriminatory power of the models was assessed using the concordance (c)-index. RESULTS: Of the 273 identified children, 191 (70%) met inclusion criteria. Median age was 5.8 years. Outcomes included 47 (25%) children with inflammation only, 41 (21%) with local infection, and 103 (54%) with disseminated infection. Both the full and reduced models accurately demonstrated excellent performance (full model c-index 0.83; 95% confidence interval, 0.79-0.88; reduced model 0.83; 95% confidence interval, 0.78-0.87). Model fit was also similar, indicating preference for the reduced model. Variables in this model included CRP, pulse, temperature, and an interaction term for pulse and temperature. The odds of a more severe outcome increased by 30% for every 10 U increase in CRP. CONCLUSIONS: Clinical and laboratory data obtained in the emergency department may be used to accurately differentiate pediatric MSKI severity. The predictive algorithm in this study stratifies pediatric MSKI severity at presentation irrespective of tissue involvement and anatomic diagnosis. Prospective studies are needed to validate model performance and clinical utility. LEVEL OF EVIDENCE: Level II prognostic study. PMID- 27682510 TI - PDGFRalpha Regulates Follicular Cell Differentiation Driving Treatment Resistance and Disease Recurrence in Papillary Thyroid Cancer. AB - Dedifferentiation of follicular cells is a central event in resistance to radioactive iodine and patient mortality in papillary thyroid carcinoma (PTC). We reveal that platelet derived growth factor receptor alpha (PDGFRalpha) specifically drives dedifferentiation in PTC by disrupting the transcriptional activity of thyroid transcription factor-1 (TTF1). PDGFRalpha activation dephosphorylates TTF1 consequently shifting the localization of this transcription factor from the nucleus to the cytoplasm. TTF1 is required for follicular cell development and disrupting its function abrogates thyroglobulin production and sodium iodide transport. PDGFRalpha also promotes a more invasive and migratory cell phenotype with a dramatic increase in xenograft tumor formation. In patient tumors we confirm that nuclear TTF1 expression is inversely proportional to PDGFRalpha levels. Patients exhibiting PDGFRalpha at time of diagnosis are three times more likely to exhibit nodal metastases and are 18 times more likely to recur within 5years than those patients lacking PDGFRalpha expression. Moreover, high levels of PDGFRalpha and low levels of nuclear TTF1 predict resistance to radioactive iodine therapy. We demonstrate in SCID xenografts that focused PDGFRalpha blockade restores iodide transport and decreases tumor burden by >50%. Focused PDGFRalpha inhibitors, combined with radioactive iodine, represent an additional avenue for treating patients with aggressive variants of PTC. PMID- 27682513 TI - A definitive blood test for post-infectious irritable bowel syndrome? PMID- 27682514 TI - Hepatocellular Carcinoma With Foamy Histiocyte-Like Component. PMID- 27682516 TI - Procalcitonin levels predict identification of bacterial strains in blood cultures of septic patients: effect measures of association. PMID- 27682515 TI - Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study. AB - OBJECTIVES: To investigate the cardiovascular safety of non-steroidal anti inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs. DESIGN: Nested case-control study. SETTING: Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom). PARTICIPANTS: Adult individuals (age >=18 years) who started NSAID treatment in 2000-10. Overall, 92 163 hospital admissions for heart failure were identified and matched with 8 246 403 controls (matched via risk set sampling according to age, sex, year of cohort entry). MAIN OUTCOME MEASURE: Association between risk of hospital admission for heart failure and use of 27 individual NSAIDs, including 23 traditional NSAIDs and four selective COX 2 inhibitors. Associations were assessed by multivariable conditional logistic regression models. The dose-response relation between NSAID use and heart failure risk was also assessed. RESULTS: Current use of any NSAID (use in preceding 14 days) was found to be associated with a 19% increase of risk of hospital admission for heart failure (adjusted odds ratio 1.19; 95% confidence interval 1.17 to 1.22), compared with past use of any NSAIDs (use >183 days in the past). Risk of admission for heart failure increased for seven traditional NSAIDs (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and two COX 2 inhibitors (etoricoxib and rofecoxib). Odds ratios ranged from 1.16 (95% confidence interval 1.07 to 1.27) for naproxen to 1.83 (1.66 to 2.02) for ketorolac. Risk of heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib used at very high doses (>=2 defined daily dose equivalents), although some confidence intervals were wide. Even medium doses (0.9-1.2 defined daily dose equivalents) of indomethacin and etoricoxib were associated with increased risk. There was no evidence that celecoxib increased the risk of admission for heart failure at commonly used doses. CONCLUSIONS: The risk of hospital admission for heart failure associated with current use of NSAIDs appears to vary between individual NSAIDs, and this effect is dose dependent. This risk is associated with the use of a large number of individual NSAIDs reported by this study, which could help to inform both clinicians and health regulators. PMID- 27682517 TI - Diabetes impairs heart mitochondrial function without changes in resting cardiac performance. AB - Diabetes is a chronic disease associated to a cardiac contractile dysfunction that is not attributable to underlying coronary artery disease or hypertension, and could be consequence of a progressive deterioration of mitochondrial function. We hypothesized that impaired mitochondrial function precedes Diabetic Cardiomyopathy. Thus, the aim of this work was to study the cardiac performance and heart mitochondrial function of diabetic rats, using an experimental model of type I Diabetes. Rats were sacrificed after 28days of Streptozotocin injection (STZ, 60mgkg-1, ip.). Heart O2 consumption was declined, mainly due to the impairment of mitochondrial O2 uptake. The mitochondrial dysfunction observed in diabetic animals included the reduction of state 3 respiration (22%), the decline of ADP/O ratio (~15%) and the decrease of the respiratory complexes activities (22-26%). An enhancement in mitochondrial H2O2 (127%) and NO (23%) production rates and in tyrosine nitration (58%) were observed in heart of diabetic rats, with a decrease in Mn-SOD activity (~50%). Moreover, a decrease in contractile response (38%), inotropic (37%) and lusitropic (58%) reserves were observed in diabetic rats only after a beta-adrenergic stimulus. Therefore, in conditions of sustained hyperglycemia, heart mitochondrial O2 consumption and oxidative phosphorylation efficiency are decreased, and H2O2 and NO productions are increased, leading to a cardiac compromise against a work overload. This mitochondrial impairment was detected in the absence of heart hypertrophy and of resting cardiac performance changes, suggesting that mitochondrial dysfunction could precede the onset of diabetic cardiac failure, being H2O2, NO and ATP the molecules probably involved in mitochondrion-cytosol signalling. PMID- 27682518 TI - Inhibition of endogenous thioredoxin-1 in the heart of transgenic mice does not confer cardioprotection in ischemic postconditioning. AB - Thioredoxin-1 maintains the cellular redox status and decreases the infarct size in ischemia/reperfusion injury. However, whether the increase of thioredoxin-1 expression or its lack of activity modifies the protection conferred by ischemic postconditioning has not been yet elucidated. The aim was to evaluate if the thioredoxin-1 overexpression enhances the posctconditioning protective effect, and whether the lack of the activity abolishes the reduction of the infarct size. Wild type mice hearts, transgenic mice hearts overexpressing thioredoxin-1, and a dominant negative mutant (C32S/C35S) of thioredoxin-1 were used. The hearts were subjected to 30min of ischemia and 120min of reperfusion (Langendorff) (I/R group) or to postconditioning protocol (PostC group). The infarct size in the Wt PostC group decreased in comparison to the Wt-I/R group (54.6+/-2.4 vs. 39.2+/ 2.1%, p<0.05), but this protection was abolished in DN-Trx1-PostC group (49.7+/ 1.1%). The ischemia/reperfusion and postconditioning in mice overexpressing thioredoxin-1 reduced infarct size at the same magnitude (35.9+/-2.1 and 38.4+/ 1.3%, p<0.05 vs. Wt-I/R). In Wt-PostC, Trx1-I/R and Trx1- PostC, Akt and GSK3beta phosphorylation increased compared to Wt-I/R, without changes in DN-Trx1 groups. In conclusion, given that the cardioprotection conferred by thioredoxin-1 overexpression and postconditioning, is accomplished through the activation of the Akt/GSK3beta survival pathway, no synergic effect was evidenced. Thioredoxin 1 plays a key role in the postconditioning, given that when this protein is inactive the cardioprotective mechanism was abolished. Thus, diverse comorbidities or situations modifying the thioredoxin activity, could explain the absence of this strong mechanism of protection in different clinical situations. PMID- 27682519 TI - Influence of P2X receptors on renal medullary circulation is not altered by angiotensin II pretreatment. AB - BACKGROUND: Purine P2X and P2Y receptors (P2-R) are involved in control of renal circulation, especially in the medulla, wherein they appear to interact with angiotensin II (Ang II). Our experimental approach enabled examination of interaction with Ang II per se, in the absence of blood pressure elevation. In this whole-kidney functional study we focused on the influence of P2X1-R on perfusion of the renal medulla. METHODS: Acute experiments were conducted with normal rats, untreated or subjected to two weeks' infusion of Ang II (osmotic minipumps). Urethane was used for anesthesia because in Ang II-treated rats it normalized elevated blood pressure. MRS2159, a P2X1-R inhibitor, was infused intravenously or directly into the medulla. Renal blood flow (RBF, Transonic renal artery probe), perfusion of the outer and inner medulla (OM-BF, IM-BF; laser-Doppler fluxes), and sodium and water excretion and urine osmolality (Uosm) were measured. RESULTS: In untreated rats intravenous MRS2159 unexpectedly decreased RBF by 12+/-4% (p<0.02) and IM-BF by 7+/-2% (p<0.05). In Ang II pretreated rats the inhibitor tended to increase RBF while OM-BF and IM-BF increased 14+/-5% and 12+/-2%, respectively (p<0.05 for both). Renal excretion was not affected, with or without Ang II treatment, while Uosm increased by about 150mosmol/kg H2O (p<0.05). Intramedullary MRS2159 increased IM-BF only, by 21+/ 5% in untreated and 16+/-3% in Ang II-treated rats (p<0.04 for both). CONCLUSIONS: Tonic activity of P2X1 receptors participates in control of renal medullary perfusion and of the tubular processes involved in urine concentration, neither effect is modified by Ang II pretreatment. PMID- 27682520 TI - X-ray diffraction analysis of spontaneously draining calcinosis in scleroderma patients. AB - OBJECTIVES: Calcium hydroxyapatite (HA) is reported to be the major constituent of soft tissue calcinosis in patients with scleroderma (systemic sclerosis, SSc). Mechanical stress and local tissue hypoxia are thought to be important in the pathogenesis of SSc calcinosis. We sought to analyse spontaneously draining material from calcinosis sites in SSc patients using X-ray diffraction (XRD). METHOD: With approval from our local Institutional Review Board (IRB), eligible SSc patients consented to submit their spontaneously draining calcinosis samples for XRD analysis. All patients met the American College of Rheumatology (ACR) criteria for definite SSc. XRD data were used to determine how much solid phase was present (e.g. HA vs. other calcium phosphate phases) and the percentage of crystalline components. Pertinent clinical data were collected. RESULTS: Draining calcinosis was submitted mostly from the hands of 10 female patients with advanced SSc, whose mean disease duration was 16 (range 9-29) years; six had diffuse cutaneous SSc and four had limited SSc. All 10 developed calcinosis later in their disease course; seven had extensive deposits affecting multiple sites. XRD confirmed that HA was the only crystalline material. However, HA was the minor component and most samples contained more than 50% organic material. Solid samples generally contained more HA and fluid samples contained HA in suspension. CONCLUSIONS: In this large series of SSc calcinosis analysis, XRD confirmed that HA was the only inorganic material that formed less than 50% of most draining samples. More research is needed to fully characterize and improve our understanding of calcinosis formation in SSc. PMID- 27682521 TI - Re: Does Exposure Prediction Bias Health-effect Estimation? The Relationship Between Confounding Adjustment and Exposure Prediction. PMID- 27682522 TI - Re: Modeling the Effects of E-cigarettes on Smoking Behavior: Implications for Future Adult Smoking Prevalence. PMID- 27682523 TI - The Authors Respond. PMID- 27682524 TI - Commentary: Multiple Causes of Death: The Importance of Substantive Knowledge in the Big Data Era. PMID- 27682526 TI - Advanced nursing scheme will give recognition where it's due. AB - What's your job title? Chances are it's one of the many traditional monikers, such as staff nurse, that the profession has used for decades. PMID- 27682527 TI - Funding cuts for CPD put NHS changes in danger. AB - Cuts to continuing professional development (CPD) funding for nurses in England could jeopardise the transformation of NHS services, academics have warned. PMID- 27682525 TI - Implications of the Definition of an Episode of Care Used in the Comprehensive Care for Joint Replacement Model. AB - Importance: Under the Comprehensive Care for Joint Replacement (CJR) model, hospitals are held accountable for nearly all Medicare payments that occur during the initial hospitalization until 90 days after hospital discharge (ie, the episode of care). It is not known whether unrelated expenditures resulting from this "broad" definition of an episode of care will affect participating hospitals' average episode-of-care payments. Objective: To compare the CJR program's broad definition of an episode of care with a clinically narrow definition of an episode of care. Design, Setting, and Participants: We identified Medicare claims for 23 251 patients in Michigan who were Medicare beneficiaries and who underwent joint replacement during the period from 2011 through 2013 at hospitals located in metropolitan statistical areas. Using specifications from the CJR model and the clinically narrow Hospital Compare payment measure, we constructed episodes of care and calculated 90-day episode payments. We then compared hospitals' average 90-day episode payments using the 2 definitions of an episode of care and fit linear regression models to understand whether payment differences were associated with specific hospital characteristics (average Centers for Medicare & Medicaid Services-hierarchical condition categories risk score, rural hospital status, joint replacement volume, percentage of Medicaid discharges, teaching hospital status, number of beds, percentage of joint replacements performed on African American patients, and median income of the hospital's county). We performed analyses from July 1 through October 1, 2015. Main Outcomes and Measures: The correlation and difference between average 90-day episode payments using the broad definition of an episode of care in the CJR model and the clinically narrow Hospital Compare definition of an episode of care. Results: We identified 23 251 joint replacements (ie, episodes of care). The 90-day episode payments using the broad definition of the CJR model ranged from $17 349 to $29 465 (mean [SD] payment, $22 122 [$2600]). Episode payments were slightly lower (mean payment, $21 670) when the Hospital Compare definition was used. Both methods were strongly correlated (r = 0.99, P < .001). The average payment difference between these 2 types of episodes of care was small (mean [SD], $452 [$177]; range, $73-$1006). In our multivariable analysis, we found that the hospital characteristics examined had a minimal impact or no impact on the payment differential. Conclusions and Relevance: The average 90-day episode payments determined by both definitions of an episode of care were strongly correlated, and there was a small payment differential for most hospitals. In the context of joint replacement bundled payments, these data suggest that hospital performance will be consistent whether a broad or clinically narrow definition of an episode of care is used. PMID- 27682529 TI - NHS England launches consultation on acceptable value of gifts to staff. AB - Nurses and other NHS staff will not be able to accept gifts worth more than L50 under new proposals about conflicts of interest. PMID- 27682528 TI - Pedometers. AB - Nursing students and trainee midwives at Edinburgh Napier University have been given pedometers to boost their health and fitness after research revealed nearly 70% of nurses in Scotland are overweight. PMID- 27682530 TI - Scheme will accredit advanced-level practice. AB - A scheme that offers accreditation to advanced nurse practitioners (ANPs) will be soft-launched this autumn, the RCN has revealed. PMID- 27682532 TI - HCAs do 'nursing on the cheap'. AB - Healthcare assistants (HCAs) are doing the jobs of nurses without the equivalent pay or education, according to a report from Unison. PMID- 27682533 TI - Trust dangles carrot of cheap rent for jobseekers. AB - An NHS trust is offering nurse recruits rent-free accommodation in a bid to attract 190 band 5 staff. PMID- 27682536 TI - You work in a neglected area of health, NHS chief tells community nurses. AB - Community nurses work in an often invisible part of the health service, says the head of NHS England. PMID- 27682537 TI - 'We need to step back and say losing the bursary could be the right way to change nurse numbers'. AB - It will take at least a decade to resolve the staffing crisis in nursing, according to a leading academic. PMID- 27682538 TI - Without reporting, FGM remains a hidden crime. AB - Though it has been illegal in the UK since 1985, no one has ever been prosecuted for FGM. Under laws rolled out last year in England and Wales, nurses, midwives, doctors and teachers have a mandatory duty to report FGM cases in under-18s to police. PMID- 27682541 TI - End of life care. AB - Essential facts In July, the government announced a new commitment to improve end of life care in England in response to What's Important to Me: A Review of Choice in End of Life Care. PMID- 27682542 TI - Whole brain radiotherapy 'has no effect' in patients whose lung cancer has spread. AB - Whole brain radiotherapy makes little or no difference to survival rates or quality of life in patients with non-small cell lung cancer (NSCLC) that has spread to the brain, say researchers. PMID- 27682543 TI - Exercise can offset the risks associated with alcohol intake. AB - Keeping to the weekly recommended level of physical activity may offset some of the lethal effects of high alcohol intake, international researchers suggest. PMID- 27682544 TI - Deliver twins at 37 weeks to give them the best chance. AB - Twins should be delivered at 37 weeks to minimise stillbirths and newborn deaths, say experts who analysed more than 35,000 twin pregnancies. PMID- 27682545 TI - Antipsychotics double risk of pneumonia in Alzheimer's. AB - Taking antipsychotic drugs increases the risk of pneumonia in people with Alzheimer's disease, say researchers from the University of Eastern Finland. PMID- 27682546 TI - Drug limits heart damage in childhood chemotherapy. AB - A cardioprotective drug could help prevent long-term heart damage in children who receive chemotherapy, researchers say. PMID- 27682547 TI - From nutrition to co-production. AB - 'These three fantastic examples illustrate the breadth of nursing innovation in London,' says RCN London regional director Bernell Bussue. PMID- 27682548 TI - Celebrating the nursing degree pioneers. AB - In 1961, teenager Sandra McSwein knew what she wanted to do with her life. Coming from a medical family, she was sure that nursing was for her. PMID- 27682549 TI - Staffing levels law will bolster the front line. AB - Sustaining a sufficient, well-educated nursing workforce that can meet growing healthcare needs is an important challenge in many countries. PMID- 27682550 TI - Shaping the future of regulation. AB - With the support of government ministers, the NMC can reform its legal framework to better reflect the regulator's range of responsibilities. PMID- 27682551 TI - How wages compare. AB - In the autumn, the NHS Pay Review Body (RB) will take evidence from government, employers and nurses' unions. It will then deliberate before making recommendations on what should be a pay rise in April 2017. But as NHS nurses know only too well, this supposedly independent system has been compromised by top down pay freezes initiated by the Westminster government as part of its 'austerity' measures. PMID- 27682552 TI - HIV: an integrated approach. AB - Last month, the National HIV Nurses Association (NHIVNA) produced guidelines on advanced nursing practice in HIV care, endorsed by the RCN. PMID- 27682555 TI - Clinical trial involvement. AB - In the past, hospital-based clinical trials were led by principal investigators who were either medics or scientists with PhDs or a post-doctoral qualification. PMID- 27682556 TI - Demise of district nursing. AB - Your article highlighting problems in district nursing is well overdue (September 14). PMID- 27682557 TI - Animal magic in tending the sick. AB - Most people are given grapes or flowers when they are ill. My friend got a dead magpie from her moggie Fergus. PMID- 27682558 TI - Readers' panel - Given the NHS funding crisis, will rationing become the norm? AB - Our experts consider a hot topic of the day. PMID- 27682560 TI - Constant Therapy. AB - Designed by scientists at Boston University, this speech therapy app aims to improve everyday skills, such as speech, memory and focus, for patients recovering from a traumatic brain injury or who have aphasia, dementia or a speech-language disorder. PMID- 27682562 TI - Student life - When laughter is the best medicine - and when it is not. AB - As you progress through your placements, you will witness the extremes of the human condition. PMID- 27682563 TI - Despite all my training, nothing prepared me for a patient's death. AB - On my first mental health placement, a tragic incident resulted in the death of a service user. With almost 5 years' experience as a support worker, this was something I hadn't faced before. PMID- 27682564 TI - Finding the right person. AB - The quest for a new job will lead many nurses to an assessment centre as part, or all, of the recruitment process. PMID- 27682565 TI - Meet award-winning HIV nurse specialist Gary Barker. AB - Since he volunteered with the St John Ambulance as a teenager, Gary Barker knew he wanted to be a nurse. PMID- 27682566 TI - 'Nursing is a privileged role'. AB - Since qualifying in 1990, major trauma nurse specialist Amanda Burston has spent her career working in emergency care. She is trauma co-ordinator for the emergency department at Royal Stoke University Hospital. She became Nursing Standard's Nurse of the Year 2015 for the Safer Steps programme, a service for victims of domestic violence. PMID- 27682567 TI - Non-suicidal self-injury: clinical presentation, assessment and management. AB - Non-suicidal self-injury is a common behaviour in adolescents and young adults, and may be associated with mental health disorders, risk of suicidal behaviour (ideation and attempts), and a need for clinical services. Nurses, in particular those working in emergency departments and mental health settings, have a crucial role in the assessment, treatment and care of individuals who have self-injured. It is essential for nurses to assess an individual's risk of more serious harm or accidental death, regardless of intent. It is also important to understand the variations in non-suicidal self-injurious behaviour in terms of its presentation, features and functions, to provide appropriate person-centred care. Nurses should assist individuals in identifying the triggers or cues for their behaviour, exploring treatment options, and monitoring their behaviour and risk in the long term. This article describes the profile of people who self-injure, and the issues related to assessment and management of such patients presenting in emergency departments. A description of who self-injures and why, and how people self-injure; developmental aspects of these behaviours, including short and long term outcomes; and the available treatments is presented. PMID- 27682568 TI - Fibromyalgia: clinical features, diagnosis and management. AB - Patients with fibromyalgia experience chronic widespread pain, with associated symptoms of fatigue, sleep disturbance and memory problems. There are many therapies which may be helpful in managing the symptoms of fibromyalgia; however, these often require a process of trial and error to establish optimum management using a combination of pharmacological and non-pharmacological approaches. Nurses can support patients with fibromyalgia using a biopsychosocial approach to symptom management. Understanding the nature of fibromyalgia and management options will enable nurses to deliver holistic patient-centred care. PMID- 27682569 TI - Neutropenic sepsis. AB - What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The article discussed the causes, signs and symptoms of neutropenic sepsis in adult patients after cancer treatment. It also explored the prevention and management of this condition. PMID- 27682570 TI - Compassionate care improved my physical and mental health. AB - I met Fiona Barrett-Gray, lead nurse in respiratory illnesses at the North Carlisle Medical Practice, more than 12 years ago and her professional and compassionate care has changed my life. I know of many other patients with respiratory illnesses who she has helped cope with loneliness and panic attacks. PMID- 27682571 TI - Online. AB - 'The nurses who showed me unconditional acceptance, irrespective of whether they agreed with what I was saying, were the ones with whom I developed strong therapeutic relationships'. PMID- 27682572 TI - UK nurses are needed overseas. AB - Could UK nurse volunteers working overseas be instrumental in reducing healthcare inequalities? Joao Marcal-Grilo, writing in Nursing Older People, is adamant that UK-trained nurses have the potential to eradicate poverty worldwide and should be offered opportunities to volunteer abroad and practise alongside colleagues in low and middle-income countries. Not only will this have a positive effect on older adults who are affected by a lack of qualified staff working in developing countries, UK-trained nurses can gain new skills that can benefit nursing practice in the UK. The article provides examples of current voluntary projects in older person care taking place in Sri Lanka and Nepal. PMID- 27682573 TI - Weight management for children with severe obesity. AB - In areas where weight management services are not established, an integrated approach is required to sustain results. This article in Primary Health Care suggests using a stepped care approach using a model such as SHINE (Self, Help, Independence, Nutrition and Exercise). This model can be used to provide a holistic and integrative care pathway for children and young people with severe obesity. PMID- 27682574 TI - Physical health screening for people with mental illness. AB - People with severe mental illness are at risk of chronic physical health conditions, but physical health screening for this patient group is rarely conducted at primary or mental healthcare facilities because of gaps in services. In this article in Mental Health Practice, Emerson and colleagues discuss a quality improvement project in the US that has been improving health outcomes for patients. PMID- 27682575 TI - Big picture. AB - 'This autumn, the US will choose a new president and, with this, a change in healthcare. But how will these changes affect US citizens? Considering that the goal of healthcare reform is to improve quality and access to care, does either presidential candidate completely support this goal?' PMID- 27682576 TI - Symbiosis Studies in Microbial Ecology. PMID- 27682577 TI - Magnetic nanogel polymer of bupivacaine for ankle block in rats. AB - INTRODUCTION: In an effort of designing an alternative method for local nerve block, we demonstrated the possibility of inducing ankle block in the rat with intravenous (IV) injection of magnetic nanoparticles conjugated bupivacaine and application of a magnet at the ankle. METHODS: The anaesthetic effect of magnet directed bupivacaine-associated MNPs (NIPAAM-MAA-bupivacaine) was tested in rat using paw withdrawal latencies from thermal stimuli on the hind paw. Thirteen (13) experimental animals were grouped into two; untreated left hind paw (control group) and test group with treated right hind paw. The morphology of the synthesised nanogel was analysed using scanning electron micrograph (SEM), chemical characterisation using Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) and finally the in vivo drug release using UV spectroscopy. RESULTS: UV spectroscopy result show that, at 37 degrees C a sharp increase was observed from 24-72 h (40-75%) cumulative drug release at pH 5.3, a steady increase from 21-60% and 20-40% at pH 6.8 and 7.4m respectively. At 43 degrees C, a steady increase was observed at the three pH, 37-72%, 20-35% and 10 19% at pH 5.3, 6.8 and 7.4, respectively. It was shown also that drug release at higher pH (6.8 and 7.4) does not become significantly faster when temperature is high, compared to the release at a pH of 5.3. This depicts that the decreasing pH has more impact on the speed of the release of drug than increasing temperature. NMR and FTIR results displayed a comparable chemical structure as expected. The NMR peak displayed high purity of the final product. Morphology using SEM showed that the nanocomposite size is slightly greater than that of the nanogel, and the nanocomposite particles are nearly mono dispersed. Paw withdrawal latency highest peak of 15% was observed for NG/PU/30 at 40hours, and lowest peak for NG/30 at 50 h for the left paw. Group BU0.15 at 30 h shows the highest peak (20%) and NG/30 at 120 h shows the lowest peak for the right treated paw, which is significantly difference from the untreated left paw group (p< 0.0001). However, there wasn't a significant difference amongst NG/30, NG/Pub/15, or NG/Pub/60. CONCLUSIONS: The current study verifies the findings that we can induce ankle block in rat through IV injection administration of NIPAAM-MAA-bupivacaine complexes and the application of magnet at the ankle. We however suggest a lower temperature and pH for optimum release of this nanoanaesthetics, there is a probability of translating this mechanism to clinical practise. PMID- 27682580 TI - Extra-articular rheumatoid arthritis imaged by [18F]FDG-PET/CT. PMID- 27682579 TI - Occupational safety measures and morbidity among welders in Vellore, Southern India. AB - BACKGROUND: Welders in the unorganized occupational sector in the economically developing world are exposed to respiratory, skin, eye, ear, and neurological problems exacerbated by non-usage of personal protective equipment (PPE). OBJECTIVE: To study the frequency of health problems and the usage of PPE among welders in unorganized welding units in Vellore, India. METHODS: A cross sectional survey was conducted among 150 welders to determine the frequency of skin, ear, eye, and respiratory morbidity and the usage of PPE. A group of 150 non-welders were chosen for comparison. RESULTS: Significant differences in the frequency of skin burns, redness, hyper pigmentation, itching, eye injuries, and sensorineural deafness were observed among the welders and non-welders (P < 0.001). Hypertension was noted in 12.6% of the welders as compared to 0.7% among the non-welders. None of the welders used appropriate PPE. For welders, low educational attainment was associated with an increased risk of eye injury (P < 0.05, OR = 0.29). There was also a significant difference between sensorineural deafness and a welder having less than 10 years of welding work experience (P < 0.001, OR = 18.18) which could probably be accounted for by the healthy worker effect. CONCLUSION: Welders in this sample experienced a significant skin, eye, and ear morbidity accentuated by the non-usage of PPE. All worked without formal training and were unaware of the safe working guidelines that exist, but are not implemented for the welders in India. PMID- 27682581 TI - Mucous Secretion and Cilia Beating Defend Developing Coral Larvae from Suspended Sediments. AB - Suspended sediments produced from dredging activities, or added to the sediment budget via river runoff, are a concern for marine resource managers. Understanding the impact of suspended sediments on critical life history stages of keystone species like corals is fundamental to effective management of coastlines and reefs. Coral embryos (Acropora tenuis and A. millepora) and larvae (A. tenuis, A. millepora and Pocillopora acuta) were subjected to a range of suspended sediment concentrations of different sediment types (siliciclastic and carbonate) to assess concentration-response relationships on ecologically relevant endpoints, including survivorship and ability to metamorphose. Embryos were subjected to short (12 h) suspended sediment exposures from ages of 3-12 hours old or a long (30 h) exposure at 6 hours old. Neither the survivorship nor metamorphosis function of embryos were significantly affected by realistic sediment exposures to ~1000 mg L-1. However, some embryos exhibited a previously undescribed response to dynamically suspended sediments, which saw 10% of the embryos form negatively buoyant cocoons at siliciclastic suspended sediment concentrations >=35 mg L-1. Scanning electron and optical microscopy confirmed the presence of a coating on these embryos, possibly mucus with incorporated sediment particles. Cocoon formation was common in embryos but not in larvae, and occurred more often after exposure to siliciclastic rather than carbonate sediments. Once transferred into sediment-free seawater, functional ~36-h-old embryos began emerging from the cocoons, coinciding with cilia development. Ciliated (> 36-h-old) larvae exposed to suspended sediments for 60 h were also observed to secrete mucus and were similarly unaffected by suspended sediment concentrations to ~800 mg L-1. This study provides evidence that mucous secretion and cilia beating effectively protect coral embryos and larvae from suspended sediment and that these mechanisms may enhance their chances of successful recruitment. PMID- 27682582 TI - Incidence and Risk Factors of Refeeding Syndrome in Head and Neck Cancer Patients An Observational Study. AB - This study aimed to determine the incidence rates of refeeding phenomena (defined as a decline in p-phosphate) and refeeding syndrome (RFS; defined as development of clinical symptoms in addition to a decline in p-phosphate) in head and neck cancer patients, and to identify risk factors. Fifty-four head and neck cancer patients referred for surgery were included. Forty-six potential risk factors were registered at the baseline, and p-phosphate was measured at Days 2, 4, and 7. Eleven patients (20%) developed RFS, and twenty-eight (52%) developed refeeding phenomena. At baseline, these patients presented a higher prevalence of head and neck pain, eating difficulties, higher p-phosphate levels, lower p transferrin levels, and, in men, lower b-hemoglobin levels. Patients who developed symptoms had a decline in p-phosphate >=0.22 mmol/l. At baseline, these patients had higher p-phosphate levels, higher alcohol consumption, and lower p transferrin and p-sodium levels, as well as a higher prevalence of eating difficulties, low handgrip strength (HGS), and a history of radiation therapy. The risk factors most strongly associated with the development of refeeding phenomena and RFS were pain, eating difficulties, low HGS, high alcohol intake, and previous radiation therapy. PMID- 27682578 TI - Progress does not just come in giant leaps: adapting techniques for the study of inflammation to novel applications. AB - INTRODUCTION: Discussion of the relevance of suitable experimental models for the effective translation of drug effects to clinical inflammatory diseases has a long history. Much emphasis is placed these days on genetically transformed mice, which may have developmental drawbacks. But are established models redundant? FINDINGS: Drawn from personal experience, examples are provided of the success of tinkering with technology in the context of inflammation. These include the use of specific dietary deficiency conditions, the development of new applications for established drugs and the introduction of a variety of readouts to assess outcome in studies on established disease models. Such approaches have been used to demonstrate inflammation-modulating effects of prostaglandin E, in the development of ebselen, for the introduction of immunomodulatory macrolide drugs and in new approaches to the therapy of multiple sclerosis. CONCLUSION: Fine tuning of experimental approaches and evaluation technologies can often still provide innovative, clinically relevant insights into the potential beneficial effects of drugs and pharmacological agents. PMID- 27682583 TI - Functional nanoscale coupling of Lyn kinase with IgE-FcepsilonRI is restricted by the actin cytoskeleton in early antigen-stimulated signaling. AB - The allergic response is initiated on the plasma membrane of mast cells by phosphorylation of the receptor for immunoglobulin E (IgE), FcepsilonRI, by Lyn kinase after IgE-FcepsilonRI complexes are cross-linked by multivalent antigen. Signal transduction requires reorganization of receptors and membrane signaling proteins, but this spatial regulation is not well defined. We used fluorescence localization microscopy (FLM) and pair-correlation analysis to measure the codistribution of IgE-FcepsilonRI and Lyn on the plasma membrane of fixed cells with 20- to 25-nm resolution. We directly visualized Lyn recruitment to IgE FcepsilonRI within 1 min of antigen stimulation. Parallel FLM experiments captured stimulation-induced FcepsilonRI phosphorylation and colocalization of a saturated lipid-anchor probe derived from Lyn's membrane anchorage. We used cytochalasin and latrunculin to investigate participation of the actin cytoskeleton in regulating functional interactions of FcepsilonRI. Inhibition of actin polymerization by these agents enhanced colocalization of IgE-FcepsilonRI with Lyn and its saturated lipid anchor at early stimulation times, accompanied by augmented phosphorylation within FcepsilonRI clusters. Ising model simulations provide a simplified model consistent with our results. These findings extend previous evidence that IgE-FcepsilonRI signaling is initiated by colocalization with Lyn in ordered lipid regions and that the actin cytoskeleton regulates this functional interaction by influencing the organization of membrane lipids. PMID- 27682584 TI - Arl13b regulates Shh signaling from both inside and outside the cilium. AB - The regulatory GTPase Arl13b localizes to primary cilia, where it regulates Sonic hedgehog (Shh) signaling. Missense mutations in ARL13B can cause the ciliopathy Joubert syndrome, while the mouse null allele is embryonic lethal. We used mouse embryonic fibroblasts as a system to determine the effects of Arl13b mutations on Shh signaling. We tested a total of seven different mutants, three JS-causing variants, two point mutants predicted to alter guanine nucleotide handling, one that disrupts cilia localization, and one that prevents palmitoylation and thus membrane binding, in assays of transcriptional and non-transcriptional Shh signaling. We found that mutations disrupting Arl13b's palmitoylation site, cilia localization signal, or GTPase handling altered the Shh response in distinct assays of transcriptional or non-transcriptional signaling. In contrast, JS causing mutations in Arl13b did not affect Shh signaling in these same assays, suggesting these mutations result in more subtle defects, likely affecting only a subset of signaling outputs. Finally, we show that restricting Arl13b from cilia interferes with its ability to regulate Shh-stimulated chemotaxis, despite previous evidence that cilia themselves are not required for this non transcriptional Shh response. This points to a more complex relationship between the ciliary and non-ciliary roles of this regulatory GTPase than previously envisioned. PMID- 27682585 TI - Perturbation of neddylation-dependent NF-kappaB responses in the intestinal epithelium drives apoptosis and inhibits resolution of mucosal inflammation. AB - Recent work has revealed a central role for neddylation (the conjugation of a Nedd8-moiety to Cullin proteins) in the fine tuning of the NF-kappaB response (via Cullin-1). In the present study, we investigated the contribution of Cullin 1 neddylation and NF-kappaB signaling to mucosal inflammatory responses in vitro and in vivo. Initial in vitro studies using cultured intestinal epithelial cells revealed that the neddylation inhibitor MLN4924 prominently induces the deneddylation of Cullin-1. Parallel western blot, luciferase reporter and gene target assays identified MLN4924 as a potent inhibitor of intestinal epithelial NF-kappaB. Subsequent studies revealed that MLN4924 potently induces epithelial apoptosis but only in the presence of additional inflammatory stimuli. In vivo administration of MLN4924 (3 mg/kg/d) in a TNBS-induce colitis model significantly accentuated disease severity. Indeed, MLN4924 resulted in worsened clinical scores and increased mortality early in the inflammatory response. Histologic analysis of the colon revealed that neddylation inhibition results in increased tissue damage and significantly increased mucosal apoptosis as determined by TUNEL and cleaved caspase-3 staining, particularly prominent within the epithelium. Extensions of these studies revealed that ongoing inflammation is associated with significant loss of deneddylase-1 (SENP8) expresssion. These studies reveal that intact Cullin-1 neddylation is central to resolution of acute inflammation. PMID- 27682586 TI - Neurite outgrowth is driven by actin polymerization even in the presence of actin polymerization inhibitors. AB - Actin polymerization is a universal mechanism to drive plasma membrane protrusion in motile cells. One apparent exception to this rule is continuing, or even accelerated outgrowth of neuronal processes in the presence of actin polymerization inhibitors. This fact together with a key role of microtubule dynamics in neurite outgrowth led to the concept that microtubules directly drive plasma membrane protrusion, either in the course of polymerization or motor driven sliding. Surprisingly, a possibility that unextinguished actin polymerization drives neurite outgrowth in the presence of actin drugs was not explored. We show that cultured hippocampal neurons treated with cytochalasin D or latrunculin B contained dense accumulations of branched actin filaments at ~50% of neurite tips at all tested drug concentrations (1-10 MUM). Actin polymerization was required for neurite outgrowth, because only low concentrations of either inhibitor increased the length and/or a number of neurites, whereas high concentrations inhibited neurite outgrowth. Importantly, neurites undergoing active elongation invariably contained a bright F-actin patch at the tip, whereas actin-depleted neurites never elongated, even though they still contained dynamic microtubules. Stabilization of microtubules by taxol treatment did not stop elongation of cytochalasin d-treated neurites. We conclude that actin polymerization is indispensable for neurite elongation. PMID- 27682587 TI - Molecular basis of Kar9-Bim1 complex function during mating and spindle positioning. AB - The Kar9 pathway promotes nuclear fusion during mating and spindle alignment during metaphase in budding yeast. How Kar9 supports the different outcome of these two divergent processes is an open question. Here, we show that three sites in the C-terminal disordered domain of Kar9 mediate tight Kar9 interaction with the C-terminal dimerization domain of Bim1 (EB1 orthologue). Site1 and Site2 contain SxIP motifs; however, Site3 defines a novel type of EB1-binding site. Whereas Site2 and Site3 mediate Kar9 recruitment to microtubule tips, nuclear movement and karyogamy, solely Site2 functions in spindle positioning during metaphase. Site1 in turn plays an inhibitory role during mating. Additionally, the Kar9-Bim1 complex is involved in microtubule-independent activities during mating. Together, our data reveal how multiple and partially redundant EB1 binding sites provide a microtubule-associated protein with the means to modulate its biochemical properties to promote different molecular processes during cell proliferation and differentiation. PMID- 27682588 TI - Tay-Sachs disease mutations in HEXA target the alpha chain of hexosaminidase A to endoplasmic reticulum-associated degradation. AB - Loss of function of the enzyme beta-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay-Sachs disease (TSD). It has been proposed that mutations in the alpha chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA alpha mutants, seeking to identify relevant cellular quality control mechanisms. The alpha mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type alpha. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA beta chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant alpha degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant alpha folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD. PMID- 27682589 TI - Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice. AB - Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria and a decrease in mature lysosomes. The few developed sperm had disrupted axonemes and some retained cytoplasmic lobe components on the flagella. ODF2 and SPAG16L, two sperm flagella proteins failed to be incorporated into sperm tails of the mutant mice, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of IFT-B complex, and IFT140, a component of IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components. PMID- 27682591 TI - Genomic Selection Improves Heat Tolerance in Dairy Cattle. AB - Dairy products are a key source of valuable proteins and fats for many millions of people worldwide. Dairy cattle are highly susceptible to heat-stress induced decline in milk production, and as the frequency and duration of heat-stress events increases, the long term security of nutrition from dairy products is threatened. Identification of dairy cattle more tolerant of heat stress conditions would be an important progression towards breeding better adapted dairy herds to future climates. Breeding for heat tolerance could be accelerated with genomic selection, using genome wide DNA markers that predict tolerance to heat stress. Here we demonstrate the value of genomic predictions for heat tolerance in cohorts of Holstein cows predicted to be heat tolerant and heat susceptible using controlled-climate chambers simulating a moderate heatwave event. Not only was the heat challenge stimulated decline in milk production less in cows genomically predicted to be heat-tolerant, physiological indicators such as rectal and intra-vaginal temperatures had reduced increases over the 4 day heat challenge. This demonstrates that genomic selection for heat tolerance in dairy cattle is a step towards securing a valuable source of nutrition and improving animal welfare facing a future with predicted increases in heat stress events. PMID- 27682593 TI - Synthesis of Triptycene-Substituted Azapentacene and Azahexacene Derivatives. AB - We describe the synthesis and characterization of novel iptycene-substituted azaacenes by using either a classic condensation route (diamine plus ortho quinone) and/or a Pd-catalyzed coupling of an aromatic diamine with an aromatic dihalide. The attachment of an iptycene unit leads to a significant blueshift (15 nm) in the UV/Vis spectra of these azaacenes. The iptycene unit stabilizes a hexaazahexacene with a lambdamax abs of 833 nm. By employing 5,6 diamino(benzothiadiazole) as a synthon for tetraaminobenzene, we could prepare the symmetrical bis-triptycene-substituted tetraazapentacene in high yields. PMID- 27682590 TI - Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein-coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, here we combine traditional biochemical approaches with superresolution microscopy methods. A novel interaction specific to PDAC is identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2). Although MOR and SSTR2 did not colocalize in healthy pancreatic cells or matching healthy patient tissues, the pair did significantly colocalize in pancreatic cancer cells, multicellular tumor spheroids, and cancerous patient tissues. Moreover, this association in pancreatic cancer cells correlated with functional cross-talk and increased metastatic potential of cells. Coactivation of MOR and SSTR2 in PDAC cells led to increased expression of mesenchymal markers and decreased expression of an epithelial marker. Together these results suggest that the MOR-SSTR2 heteromer may constitute a novel therapeutic target for PDAC. PMID- 27682595 TI - Stacking up Cav3.2 channels. PMID- 27682594 TI - Long Term Outcome after Application of the Angio-Seal Vascular Closure Device in Minipigs. AB - Minipigs are frequently used in (neuro-)interventional research. Longitudinal experiments may require repeated vessel access via the femoral artery. Anticoagulation and incompliance of the animals necessitates the use of a vascular closure device (VCD). The effects of the Angio-Seal VCD in minipigs were longitudinally assessed. Minipig (42+/-8.4 kg body weight) femoral arteries were sealed using the 8F (n = 6) or 6F (n = 7) Angio-Seal VCD. The pre-interventional femoral artery diameter was 5.1+/-0.4 mm (4.3-5.8 mm). Sealed puncture sites were analysed angiographically as well as by computed tomography angiography (CTA) for a mean period of 14.1+/-8.0 weeks (1-22 weeks). All animals were constantly treated with acetylsalicylic acid (ASS) (450 mg/d (n = 7) or 100 mg/d (n = 1)) and clopidogrel (75 mg/d (n = 8)). Non-instrumented (n = 2) and arteries sealed using the VCD (n = 2) were examined histologically. No postoperative hemorrhagic complications were observed. Three arteries were occluded after VCD placement (1 animal diagnosed after 4 weeks (8F), 2 animals after 1 week (6F)) and remained so until the end of the experiments after 22, 12 and 4 weeks, respectively. In one artery a 50% stenosis 8 weeks after application of a 6F Angio-Seal was detected. In 69.2% (n = 9) the VCD was applied without complications. Histopathological analysis of the sealed arterial segments showed subtotal obliteration of the vessel lumen, formation of collagenous tissue and partial damage of the internal elastic lamina. The Angio-Seal VCD prevents relevant hemorrhagic complications in minipigs treated with dual platelet inhibition, but is associated with increased vessel occlusion rates. PMID- 27682596 TI - Inhibition of transforming growth factor beta-activated kinase 1 prevents inflammation-related cartilage degradation in osteoarthritis. AB - Osteoarthritis (OA) is a common debilitating joint disorder, there's still no available disease-modifying drug for OA currently. This study aims to explore the role of TAK1 in OA pathogenesis and therapeutic efficiency of TAK1 inhibition for OA. The contribution of TAK1 to OA pathogenesis was investigated by intra articular injection of TAK1-encoding adenovirus in rats. TAK1 inhibitor 5Z-7 induced expression changes of extracellular matrix (ECM)-related genes were detected by real-time PCR. The protective effect of 5Z-7 against OA progression was evaluated in a post-traumatic OA rat model. Our results showed that intra articular injection of Ad-Tak1 induced cartilage destruction and OA-related cytokine secretion in rat joints. TAK1 inhibition by 5Z-7 efficiently blocked NF kappaB, JNK and p38 pathways activation in OA chondrocytes and synoviocytes, Meanwhile, 5Z-7 significantly decreased the expression of matrix-degrading enzymes and pro-inflammatory cytokine, while increased ECM protein expression, which are all crucial components in OA. 5Z-7 also ameliorated ECM loss in OA cartilage explants. More importantly, 5Z-7 significantly protected against cartilage destruction in a rat model of OA. In conclusion, our findings provide the first in vivo evidence that TAK1 contributes to OA by disrupting cartilage homeostasis, thus represents an ideal target for OA treatment, with 5Z-7 as a candidate therapeutic. PMID- 27682598 TI - Predictive Value of Triglyceride Glucose Index for the Risk of Incident Diabetes: A 4-Year Retrospective Longitudinal Study. AB - The Triglyceride Glucose Index (TyG index) is considered a surrogate marker of insulin resistance. The aim of this study is to investigate whether the TyG index has a predictive role in identifying individuals with a high risk of incident diabetes and to compare it with other indicators of metabolic health. A total 2900 non-diabetic adults who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital was divided into four subgroups using three methods: (1) baseline TyG index; (2) obesity status (body mass index >=25 kg/m2) and cutoff value of TyG index; (3) obesity status and metabolic health, defined as having fewer than two of the five components of high blood pressure, fasting blood glucose, triglyceride, low high-density lipoprotein cholesterol, and highest decile of homeostasis model assessment-insulin resistance. The development of diabetes was assessed annually using self-questionnaire, fasting glucose, and glycated hemoglobin. We compared the risk of incident diabetes using multivariate Cox analysis. During 11623 person-years there were 101 case of incident diabetes. Subjects with high TyG index had a high risk of diabetes. For TyG index quartiles, hazard ratios (HRs) of quartiles 3 and 4 were 4.06 (p = 0.033) and 5.65 (p = 0.006) respectively. When the subjects were divided by obesity status and cutoff value of TyG index of 8.8, the subgroups with TyG index >= 8.8 regardless of obesity had a significantly high risk for diabetes (HR 2.40 [p = 0.024] and 2.25 [p = 0.048]). For obesity status and metabolic health, the two metabolically unhealthy subgroups regardless of obesity had a significantly high risk for diabetes (HRs 2.54 [p = 0.024] and 2.73 [p = 0.021]). In conclusion, the TyG index measured at a single time point may be an indicator of the risk for incident diabetes. The predictive value of the TyG index was comparable to that of metabolic health. PMID- 27682597 TI - p120-Catenin Is Required for Dietary Calcium Suppression of Oral Carcinogenesis in Mice. AB - Previous studies have shown that dietary calcium suppresses oral carcinogenesis, but the mechanism is unclear. p120-catenin (p120) is a cytoplasmic protein closely associated with E-cadherin to form the E-cadherin-beta-catenin complex and may function as a tumor suppressor in the oral epithelium. To determine whether p120 is involved in the mechanism by which dietary calcium suppresses oral carcinogenesis, The normal, low, or high calcium diet was fed control mice (designated as floxed p120 mice) or mice in which p120 was specifically deleted in the oral squamous epithelium during the adult stage (designated as p120cKO mice). All mice were exposed to a low dose of oral cancer carcinogen 4 nitroquinoline 1-oxide and rates of oral squamous cell carcinoma (OSCC) and proliferation and differentiation in the cancerous and non-cancerous oral epithelium of these mice were examined. The results showed that the low calcium diet increased rates of OSCC and proliferation of the non-cancerous oral epithelium and decreased differentiation of the non-cancerous oral epithelium, but had no effect on cancerous oral epithelium. In contrast, the high calcium diet had opposite effects. However, the effect of the dietary calcium on the rates of OSCC, proliferation, and differentiation of the non-cancerous epithelium were not seen in p120cKO mice. Based on these results, we conclude that p120 is required for dietary calcium suppression of oral carcinogenesis and oral epithelial proliferation and dietary calcium induction of oral epithelial differentiation. J. Cell. Physiol. 232: 1360-1367, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27682599 TI - A Quasi-Solid-State Li-Ion Capacitor Based on Porous TiO2 Hollow Microspheres Wrapped with Graphene Nanosheets. AB - The quasi-solid-state Li-ion capacitor is demonstrated with graphene nanosheets prepared by an electrochemical exfoliation as the positive electrode and the porous TiO2 hollow microspheres wrapped with the same graphene nanosheets as the negative electrode, using a Li-ion conducting gel polymer electrolyte. This device may be the key to bridging the gap between conventional lithium-ion batteries and supercapacitors, meanwhile meeting the safety demands of electronic devices. PMID- 27682600 TI - Impact of pharmacist interventions on cost avoidance in an ambulatory cancer center. AB - Objective To provide a foundation to justify the presence of a full-time clinical pharmacist in the ambulatory cancer center in addition to an existing centralized pharmacist through cost avoidance calculation and patient and staff satisfaction surveys. Methods The prospective, pilot study took place in an ambulatory cancer center over four weeks in 2014. Cost avoidance values were assigned to interventions performed by a pharmacy resident, who was present in the ambulatory cancer center during clinic hours, along with a centralized oncology pharmacist routinely working with the cancer center. Anonymous patient and staff satisfaction surveys based on a 5-point Likert scale were distributed to assess the perceived benefit of a pharmacist located in the ambulatory cancer center. Results Data collection took place over approximately one month. After evaluation of 962 interventions from both pharmacists, the estimated cost avoidance was US$282,741 per pharmacist per year, yielding a net benefit of US$138,441. The most common interventions made by the resident included chemotherapy regimen review (n = 290, 69%) and patient counseling (n = 102, 24%), while the majority of the centralized pharmacist's interventions was chemotherapy regimen review (n = 525, 97%). Results from the anonymous patient and staff surveys revealed an overall positive perception of the pharmacy resident while in the ambulatory cancer center. Conclusion A full-time clinical pharmacist in an ambulatory cancer center is both financially beneficial and positively perceived by patients and staff. PMID- 27682601 TI - Erratum to: Low-dose brachytherapy for early stage penile cancer: a 20-year single-institution study (73 patients). PMID- 27682603 TI - Non-invasive imaging of retinal blood flow in myeloproliferative neoplasms. AB - PURPOSE: To study the circulation in the retinal vessels in patients with blood dyscrasia due to myeloproliferative neoplasms using non-invasive retinal imaging. METHODS: Prospective consecutive case series of seven treatment-naive patients with chronic myeloid leukaemia (n = 2), polycythemia vera (n = 4), essential thrombocytosis (n = 1) examined before and after cytoreductive treatment. We investigated retinal circulation with motion-contrast imaging, retinal oximetry and spectral-domain optical coherence tomography. RESULTS: Retinal venous blood velocity increased by 8.14% (CI95 3.67% to 12.6%, p = 0.004) and retinal arterial oxygen saturation increased by 7.23% (CI95 2.9% to 11.6%, p = 0.010) at follow-up (mean 12 weeks, range 5-14 weeks) where complete haematological remission had been achieved by cytoreductive treatment. Abnormal optical coherence tomography reflectivity patterns were present at baseline in patients with chronic myeloid leukaemia and were replaced by normal patterns at follow-up. Retinopathy, in the form of cotton-wool spots and retinal haemorrhages, was found at presentation in the two patients with chronic myeloid leukaemia and in one patient with polycythemia vera. The retinopathy had resolved at follow-up in all patients. CONCLUSION: With non-invasive retinal imaging, we were able to demonstrate increased retinal venous blood velocity, increased retinal arterial blood oxygenation and normalization of intravascular reflectivity patterns after successful treatment of myeloproliferative neoplasms. Larger prospective studies are needed to assess the prognostic value of these non-invasive imaging methods in predicting circulatory complications in myeloproliferative neoplasms. PMID- 27682604 TI - Xenopus laevis and Emerging Amphibian Pathogens in Chile. AB - Amphibians face an extinction crisis with no precedence. Two emerging infectious diseases, ranaviral disease caused by viruses within the genus Ranavirus and chytridiomycosis due to Batrachochytrium dendrobatidis (Bd), have been linked with amphibian mass mortalities and population declines in many regions of the globe. The African clawed frog (Xenopus laevis) has been indicated as a vector for the spread of these pathogens. Since the 1970s, this species has been invasive in central Chile. We collected X. laevis and dead native amphibians in Chile between 2011 and 2013. We conducted post-mortem examinations and molecular tests for Ranavirus and Bd. Eight of 187 individuals (4.3 %) tested positive for Ranavirus: seven X. laevis and a giant Chilean frog (Calyptocephallela gayi). All positive cases were from the original area of X. laevis invasion. Bd was found to be more prevalent (14.4 %) and widespread than Ranavirus, and all X. laevis Bd positive animals presented low to moderate levels of infection. Sequencing of a partial Ranavirus gene revealed 100 % sequence identity with Frog Virus 3. This is the first report of Ranavirus in Chile, and these preliminary results are consistent with a role for X. laevis as an infection reservoir for both Ranavirus and Bd. PMID- 27682602 TI - Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case control study. AB - BACKGROUND: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D. METHODS: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods. RESULTS: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age. CONCLUSIONS: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas. TRIAL REGISTRATION: Clinical-Trial.gov NCT02212522 . Registered August 6, 2014. PMID- 27682605 TI - Microbial Indicators, Opportunistic Bacteria, and Pathogenic Protozoa for Monitoring Urban Wastewater Reused for Irrigation in the Proximity of a Megacity. AB - In Latin America and the Caribbean, with a population of approximately 580 million inhabitants, less than 20 % of wastewater is treated. Megacities in this region face common challenges and problems related with water quality and sanitation, which require urgent actions, such as changes in the sustainable use of water resources. The Mexico City Metropolitan Area is one of the most populous urban agglomerations in the world, with over 20 million inhabitants, and is no exception to the challenges of sustainable water management. For more than 100 years, wastewater from Mexico City has been transported north to the Mezquital Valley, which is ranked as the largest wastewater-irrigated area in the world. In this study, bacteria and pathogenic protozoa were analyzed to determine the association between the presence of such microorganisms and water types (WTs) across sampling sites and seasons in Mexico City and the Mezquital Valley. Our results show a difference in microbiological water quality between sampling sites and WTs. There is no significant interaction between sampling sites and seasons in terms of bacterial concentration, demonstrating that water quality remains constant at each site regardless of whether it is the dry or the rainy season. The results illustrate the quantity of these microorganisms in wastewater, provide a current diagnosis of water quality across the area which could affect the health of residents in both Mexico City and the Mezquital Valley, and demonstrate the need to transition in the short term to treat wastewater from a local to a regional scale. PMID- 27682606 TI - Biological embedding: evaluation and analysis of an emerging concept for nursing scholarship. AB - AIM: The purpose of this paper was to report the analysis of the concept of biological embedding. BACKGROUND: Research that incorporates a life course perspective is becoming increasingly prominent in the health sciences. Biological embedding is a central concept in life course theory and may be important for nursing theories to enhance our understanding of health states in individuals and populations. Before the concept of biological embedding can be used in nursing theory and research, an analysis of the concept is required to advance it towards full maturity. DESIGN: Concept analysis. DATA SOURCES: PubMed, CINAHL and PsycINFO were searched for publications using the term 'biological embedding' or 'biological programming' and published through 2015. METHODS: An evaluation of the concept was first conducted to determine the concept's level of maturity and was followed by a concept comparison, using the methods for concept evaluation and comparison described by Morse. RESULTS: A consistent definition of biological embedding - the process by which early life experience alters biological processes to affect adult health outcomes - was found throughout the literature. The concept has been used in several theories that describe the mechanisms through which biological embedding might occur and highlight its role in the development of health trajectories. Biological embedding is a partially mature concept, requiring concept comparison with an overlapping concept - biological programming - to more clearly establish the boundaries of biological embedding. CONCLUSIONS: Biological embedding has significant potential for theory development and application in multiple academic disciplines, including nursing. PMID- 27682607 TI - Plasmadiafiltration ameliorating gut mucosal barrier dysfunction and improving survival in porcine sepsis models. AB - BACKGROUND: The object of this study is to explore whether the plasmadiafiltration (PDF) is more effective in improving the intestinal mucosal barrier function by removing more key large molecular inflammatory mediators and then prolonging the survival time. METHODS: Totally, 24 porcine sepsis models induced by cecal ligation and puncture (CLP) operation were randomly divided into three groups: PDF group, high-volume hemofiltration (HVHF) group, and control group, and received 8 h treatment, respectively. The expression of ZO-1 and occludin in intestinal mucosal epithelial cells were detected by immunohistochemistry, and apoptotic protein caspase-3-positive lymphocytes were signed in mesenteric lymph nodes by TUNEL staining. The hemodynamic parameters were measured by invasive cavity detection. The tumor necrosis factor alpha (TNFalpha) and high-mobility group protein 1 (HMGB1) were tested by ELISA method. And then, the survival curves with all-cause death were compared with three groups. RESULTS: PDF led to a superior reversal of sepsis-related hemodynamic impairment and serum biochemistry abnormalities and resulted in longer survival time compared with HVHF and control (p < 0.01). Definitive protection from excessive TNF-alpha and HMGB1 response were only achieved by PDF. A more regular distribution pattern of ZO-1 and occludin along the epithelium was found in PDF animals (p < 0.01). The presence of apoptotic lymphocytes was significantly reduced in the PDF animals (p < 0.01). CONCLUSIONS: PDF can effectively eliminate more pivotal inflammatory mediators of TNFalpha and HMGB1 and reduce the inflammation damage of the intestinal mucosal barrier and apoptosis of lymphocyte then improve the circulation function and prolong the survival time. PMID- 27682610 TI - Hyperthermic intraperitoneal chemotherapy as palliative treatment for malignant ascites A single-center experience and a review of the literature. AB - : Malignant ascites is an abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal cancer dissemination. This clinical condition could represent the terminal evolution of a lethal disease and could influence the prognosis, severely impairing the patients' quality of life. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk; diuretics, paracentesis, peritoneo-venous shunts and intraperitoneal biologic agents like anti-VEGF molecules, metalloproteinase inhibitors and immunomodulators are included. None of these approaches have been established as a standard of care because of their low efficacy or severe side effects. The last two decades saw the emergence of cytoreductive surgery with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) as a viable therapeutic approach resulting in an effective cure against refractory malignant ascites. The following describes our experiences with 3 cases together with a literature review. KEY WORDS: Chemotherapy, HIPEC, Laparoscopy, Malignant ascites. PMID- 27682609 TI - A comparative study of the effect of Bio-Oss(r) in combination with concentrated growth factors or bone marrow-derived mesenchymal stem cells in canine sinus grafting. AB - BACKGROUND: To compare the effects of Bio-Oss(r) in combination with concentrated growth factors (CGFs) and bone marrow-derived mesenchymal stem cells (BMSCs) on bone regeneration for maxillary sinus floor augmentation in beagle dogs. METHODS: Six beagle dogs received bilateral maxillary sinus floor augmentation. Venous blood drawn from dogs was collected and centrifuged to obtain CGFs. BMSCs derived from canine bone marrow were cultured using density gradient centrifugation. The suspension of BMSCs was added onto Bio-Oss(r) granules at a density of 2 * 106 cells/ml, and the BMSCs/Bio-Oss(r) constructs were incubated for an additional 4 h before use. Twelve sinuses were grafted with a mixture of CGFs/Bio-Oss(r) , BMSCs/Bio-Oss(r) construct, or Bio-Oss(r) alone. Six months later, the bone formation of bilateral sinuses was evaluated by Micro-CT, microhardness test, histological examination, and histomorphometry. RESULTS: No adverse effect was found in these dogs. The dome-shaped augmentation protruded into the sinus cavity. Micro-CT revealed that there was significant difference in BV/TV but not in Tb. N, between groups A, B, and C. The extent of microhardness in groups A and B was significantly higher than in group C. The proportion of newly formed bone in groups A and B showed significant difference when compared to group C (P <= 0.01). The amount of residual grafts in groups A and B was significantly lower than in group C. CONCLUSIONS: Grafting with Bio-Oss(r) in combination with CGFs can increase new bone formation more efficiently than using Bio-Oss(r) alone in a canine model. PMID- 27682608 TI - Dual effectiveness of Alternaria but not Fusarium mycotoxins against human topoisomerase II and bacterial gyrase. AB - Type II DNA-topoisomerases (topo II) play a crucial role in the maintenance of DNA topology. Previously, fungi of the Alternaria genus were found to produce mycotoxins that target human topo II. These results implied the question why a fungus should produce secondary metabolites that target a human enzyme. In the current work, the homology between human topo II and its bacterial equivalent, gyrase, served as basis to study a potential dual inhibition of both enzymes by mycotoxins. A total of 15 secondary metabolites produced by fungi of the genera Alternaria and Fusarium were assessed for their impact on topo II of human and bacterial origin in the decatenation and the supercoiling assay, respectively. In line with the theory of dual topo II inhibition, six of the tested Alternaria mycotoxins were active against both enzymes, the dibenzo-alpha-pyrones alternariol (AOH) and alternariol monomethyl ether (AME), as well as the perylene quinones altertoxin I (ATX I) and II (ATX II), alterperylenol (ALP) and stemphyltoxin III (STTX III). The Alternaria metabolites altersetin (ALN), macrosporin (MAC), altenusine (ALS) and pyrenophorol (PYR) impaired the function of human topo II, but did not show any effect on gyrase. The potency to inhibit topo II activity declined in the row STTX III (initial inhibitory concentration 10 uM) > AOH (25 uM) = AME (25 uM) = ALS (25 uM) = ATX II (25 uM) > ALN (50 uM) = ATX I (50 uM) > ALP (75 uM) = PYR (75 uM) > MAC (150 uM). Inhibition of gyrase activity was most pronounced for AOH and AME (initial inhibitory concentration 10 uM) followed by ATX II (25 uM) > ATX I = ALP = STTX III (50 uM). In contrast, none of the investigated Fusarium mycotoxins deoxynivalenol (DON), fumonisin B1, fusarin C and moniliformin, as well as the Alternaria metabolite tentoxin, had any impact on the activity of neither human nor bacterial topo II. PMID- 27682612 TI - Neonatal Bartter syndrome with cholelithiasis and hydrocephalus: Rare association. AB - Neonatal Bartter syndrome (NBS) is a rare autosomal recessive renal tubular disorder. This disease is characterized by hypokalemia, hypochloremia, and metabolic alkalosis that is often associated with failure to thrive and recurrent episodes of dehydration. The combination of BS and cholelithiasis in an infant is very rare. Herein, we report a premature male infant with NBS who developed cholelithiasis and hydrocephalus on clinical follow up. We recommend that periodic routine hepatobiliary ultrasonograpic screening for cholelithiasis should be performed in patients with NBS. PMID- 27682611 TI - Molecular evidence of high rates of asymptomatic P. vivax infection and very low P. falciparum malaria in Botswana. AB - BACKGROUND: Botswana is one of eight SADC countries targeting malaria elimination by 2018. Through spirited upscaling of control activities and passive surveillance, significant reductions in case incidence of Plasmodium falciparum (0.96 - 0.01) was achieved between 2008 and 2012. As part of the elimination campaign, active detection of asymptomatic Plasmodium species by a highly sensitive method was deemed necessary. This study was carried out to determine asymptomatic Plasmodium species carriage by nested PCR in the country, in 2012. METHOD: A cross-sectional study involving 3924 apparently healthy participants were screened for Plasmodium species in 14 districts (5 endemic: Okavango, Ngami, Tutume, Boteti and Bobirwa; and 9 epidemic: North East, Francistown, Serowe Palapye, Ghanzi, Kweneng West, Kweneng East, Kgatleng, South East, and Good Hope). Venous blood was taken from each participant for a nested PCR detection of Plasmodium species. RESULTS: The parasite rates of asymptomatic Plasmodium species detected were as follows: Plasmodium falciparum, 0.16 %; Plasmodium vivax, 4.66 %; Plasmodium malariae, (Pm) 0.16 %; Plasmodium ovale, 0 %, mixed infections (P. falciparum and P. vivax), 0.055 %; and (P. vivax and P. malariae), 0.027 %, (total: 5.062 %). The high proportion of asymptomatic reservoir of P. vivax was clustered in the East, South Eastern and Central districts of the country. There appeared to be a correlation between the occurrence of P. malariae infection with P. vivax infection, with the former only occurring in districts that had substantial P. vivax circulation. The median age among 2-12 year olds for P. vivax infection was 5 years (Mean 5.13 years, interquartile range 3-7 years). The odds of being infected with P. vivax decreased by 7 % for each year increase in age (OR 0.93, 95 % CI 0.87-1.00, p = 0.056). CONCLUSION: We have confirmed low parasite rate of asymptomatic Plasmodium species in Botswana, with the exception of P.vivax which was unexpectedly high. This has implication for the elimination campaign so a follow up study is warranted to inform decisions on new strategies that take this evidence into account in the elimination campaign. PMID- 27682613 TI - Prenatal diagnosis of Gaucher disease using next-generation sequencing. AB - In the prenatal diagnosis of Gaucher disease (GD), glucocerebrosidase (GBA) activity is measured with fetal cells, and gene analysis is performed when pathogenic mutations in GBA are identified in advance. Herein is described prenatal diagnosis in a family in which two children had GD. Although prior genetic information for this GD family was not obtained, next-generation sequencing (NGS) was carried out for this family because immediate prenatal diagnosis was necessary. Three mutations were identified in this GD family. The father had one mutation in intron 3 (IVS2 + 1), the mother had two mutations in exons 3 (I[-20]V) and 5 (M85T), and child 1 had all three of these mutations; child 3 had none of these mutations. On NGS the present fetus (child 3) was not a carrier of GD-related mutations. NGS may facilitate early detection and treatment before disease onset. PMID- 27682614 TI - Ecthyma gangrenosum in an infant after liver transplantation. AB - Ecthyma gangrenosum is a rare, necrotizing, bacterial infection of the skin most commonly caused by Pseudomonas aeruginosa. It has a characteristic clinical picture starting with maculopapular eruption followed by hemorrhagic vesicle and evolving into gangrenous ulcer. Although direct skin inoculation without septicemia is also probable, usually ecthyma gangrenosum is pathognomonic for Pseudomonas septicemia, which has a mortality rate of 38-96%. Herein, we report on the case of a 9-month-old male infant diagnosed with ecthyma gangrenosum who had undergone liver transplantation approximately 6 months previously and who was under immunosuppressive treatment, in order to highlight the importance of the early diagnosis and treatment of this disease. PMID- 27682616 TI - Pediatrician role in public health: Domestic animal-related injury alerts for neonates. PMID- 27682615 TI - Anti-myelin oligodendrocyte glycoprotein antibody neuritis optica following anti NMDA receptor encephalitis. PMID- 27682617 TI - Thorium-phosphorus triamidoamine complexes containing Th-P single- and multiple bond interactions. AB - Despite the burgeoning field of uranium-ligand multiple bonds, analogous complexes involving other actinides remain scarce. For thorium, under ambient conditions only a few multiple bonds to carbon, nitrogen, oxygen, sulfur, selenium and tellurium are reported, and no multiple bonds to phosphorus are known, reflecting a general paucity of synthetic methodologies and also problems associated with stabilising these linkages at the large thorium ion. Here we report structurally authenticated examples of a parent thorium(IV)-phosphanide (Th-PH2), a terminal thorium(IV)-phosphinidene (Th=PH), a parent dithorium(IV) phosphinidiide (Th-P(H)-Th) and a discrete actinide-phosphido complex under ambient conditions (Th=P=Th). Although thorium is traditionally considered to have dominant 6d-orbital contributions to its bonding, contrasting to majority 5f orbital character for uranium, computational analyses suggests that the bonding of thorium can be more nuanced, in terms of 5f- versus 6d-orbital composition and also significant involvement of the 7s-orbital and how this affects the balance of 5f- versus 6d-orbital bonding character. PMID- 27682618 TI - Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models. AB - RATIONALE: Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease, remain unresolved. In particular, it is not known whether all VSMCs proliferate and display plasticity or whether individual cells can switch to multiple phenotypes. OBJECTIVE: To assess whether proliferation and plasticity in disease is a general characteristic of VSMCs or a feature of a subset of cells. METHODS AND RESULTS: Using multicolor lineage labeling, we demonstrate that VSMCs in injury-induced neointimal lesions and in atherosclerotic plaques are oligoclonal, derived from few expanding cells. Lineage tracing also revealed that the progeny of individual VSMCs contributes to both alpha smooth muscle actin (aSma)-positive fibrous cap and Mac3-expressing macrophage-like plaque core cells. Costaining for phenotypic markers further identified a double-positive aSma+ Mac3+ cell population, which is specific to VSMC-derived plaque cells. In contrast, VSMC-derived cells generating the neointima after vascular injury generally retained the expression of VSMC markers and the upregulation of Mac3 was less pronounced. Monochromatic regions in atherosclerotic plaques and injury induced neointima did not contain VSMC-derived cells expressing a different fluorescent reporter protein, suggesting that proliferation-independent VSMC migration does not make a major contribution to VSMC accumulation in vascular disease. CONCLUSIONS: We demonstrate that extensive proliferation of a low proportion of highly plastic VSMCs results in the observed VSMC accumulation after injury and in atherosclerotic plaques. Therapeutic targeting of these hyperproliferating VSMCs might effectively reduce vascular disease without affecting vascular integrity. PMID- 27682619 TI - Deconstructing the Alcohol Harm Paradox: A Population Based Survey of Adults in England. AB - BACKGROUND: The Alcohol Harm Paradox refers to observations that lower socioeconomic status (SES) groups consume less alcohol but experience more alcohol-related problems. However, SES is a complex concept and its observed relationship to social problems often depends on how it is measured and the demographic groups studied. Thus this study assessed socioeconomic patterning of alcohol consumption and related harm using multiple measures of SES and examined moderation of this patterning by gender and age. METHOD: Data were used from the Alcohol Toolkit Study between March and September 2015 on 31,878 adults (16+) living in England. Participants completed the AUDIT which includes alcohol consumption, harm and dependence modules. SES was measured via qualifications, employment, home and car ownership, income and social-grade, plus a composite of these measures. The composite score was coded such that higher scores reflected greater social-disadvantage. RESULTS: We observed the Alcohol Harm Paradox for the composite SES measure, with a linear negative relationship between SES and AUDIT-Consumption scores (beta = -0.036, p<0.001) and a positive relationship between lower SES and AUDIT-Harm (beta = 0.022, p<0.001) and AUDIT-Dependence (beta = 0.024, p<0.001) scores. Individual measures of SES displayed different, and non-linear, relationships with AUDIT modules. For example, social-grade and income had a u-shaped relationship with AUDIT-Consumption scores while education had an inverse u-shaped relationship. Almost all measures displayed an exponential relationship with AUDIT-Dependence and AUDIT-Harm scores. We identified moderating effects from age and gender, with AUDIT-Dependence scores increasing more steeply with lower SES in men and both AUDIT-Harm and AUDIT Dependence scores increasing more steeply with lower SES in younger age groups. CONCLUSION: Different SES measures appear to influence whether the Alcohol Harm Paradox is observed as a linear trend across SES groups or a phenomenon associated particularly with the most disadvantaged. The paradox also appears more concentrated in men and younger age groups. PMID- 27682621 TI - Are Agricultural Soils Dumps for Microplastics of Urban Origin? PMID- 27682620 TI - Distribution and characteristics of rodent picornaviruses in China. AB - Rodents are important reservoir hosts of many important zoonotic viruses. The family Picornaviridae contains clinically important pathogens that infect humans and animals, and increasing numbers of rodent picornaviruses have recently been associated with zoonoses. We collected 574 pharyngeal and anal swab specimens from 287 rodents of 10 different species from eight representative regions of China from October 2013 to July 2015. Seven representative sequences identified from six rodent species were amplified as full genomes and classified into four lineages. Three lineage 1 viruses belonged to a novel genus of picornaviruses and was more closely related to Hepatovirus than to others genera of picornaviruses based on aa homology. Lineage 2, lineage 3, and lineage 4 viruses belonged to the genera Rosavirus, Hunnivirus, and Enterovirus, respectively, representing new species. According to both phylogenetic and identity analyses, Lineage 2 viruses had a close relationship with rosavirus 2 which was recovered from the feces of a child in Gambia and Lineage 3 viruses had a close relationship with domestic animal Hunnivirus. Lineage 4 viruses provide the first evidence of these enteroviruses and their evolution in rodent hosts in China. PMID- 27682624 TI - Facile Preparation of Wurtzite CuInE2 (E = S, Se) Nanoparticles Under Solvothermal Conditions. AB - In this work, the synthesis of nanoscale CuInS2 and CuInSe2 was developed using molecular precursors of the type [(Ph3P)2CuIn(ER)4] (E = S, Se) and solvothermal reactions. Various conditions were investigated including the use of different precursors, reaction temperatures, reaction times and the addition of a secondary chalcogen source to mixtures. After optimizing conditions, nanoparticles of CuInS2 and CuInSe2 were isolated with controlled sizes in the range of 2-5 nm (wurtzite structure), which ultimately tuned the band gap energies of the materials. Characterization methods including powder X-ray diffraction, electron microscopy, and optical spectroscopy were used to investigate their structures and photophysical properties. PMID- 27682622 TI - IL-1beta, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. AB - Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT and associated bacteria by neutrophils; bacteria are subsequently killed via neutrophil ROS. Using this pyroptosis model, we now show that the pro inflammatory cytokines IL-1beta and IL-18 and inflammatory lipid mediators termed eicosanoids are required for effective clearance of bacteria downstream of pyroptosis. We further show that IL-1beta, IL-18, and eicosanoids affect this in part by mediating neutrophil recruitment to the PIT. This is in addition to our prior findings that complement is also important to attract neutrophils. Thus, the PIT initiates a robust and coordinated innate immune response involving multiple mediators that attract neutrophils to efferocytose the PIT and its entrapped bacteria. PMID- 27682623 TI - Influence of R-CHOP Therapy on Immune System Restoration in Patients with B-Cell Lymphoma. AB - OBJECTIVE: To assess the immunosuppressive effect of R-CHOP in patients with B cell lymphoma at 2 years. METHODS: Parameters of humoral and cell-mediated immunity were assessed in 89 patients with diffuse large B-cell lymphoma or follicular lymphoma before and after 6-8 cycles of R-CHOP-14 or R-CHOP-21 regimen. RESULTS: Data on pre- and posttreatment serum IgG (sIgG) levels were available for all 89 patients, while the corresponding data on serum CD20+, CD3+, CD4+, and CD8+ lymphocyte counts were available in only 43. Median sIgG levels significantly decreased from 1,221 mg/dl (baseline) to 733 mg/dl (after chemotherapy) (p < 0.001). Although CD20+ and CD4+ cell counts decreased (p < 0.001), no significant effect of chemotherapy on CD3+ and CD8+ cell counts was observed. CD20+ cell counts were restored to baseline levels at the 12-month follow-up. sIgG levels and CD4+ cell counts were not completely restored at 24 months, indicating a sustained immunosuppressive effect of R-CHOP in these patients. The incidence of infections over the 2-year period was 16.3-23.6%. CONCLUSION: The immunosuppressive effect of R-CHOP in newly diagnosed cases of B cell lymphoma tends to persist for >2 years, although sIgG levels were restored more quickly than CD4+ cell counts. PMID- 27682626 TI - Coupled Cluster Method with Single and Double Excitations Tailored by Matrix Product State Wave Functions. AB - In the past decade, the quantum chemical version of the density matrix renormalization group (DMRG) method has established itself as the method of choice for calculations of strongly correlated molecular systems. Despite its favorable scaling, it is in practice not suitable for computations of dynamic correlation. We present a novel method for accurate "post-DMRG" treatment of dynamic correlation based on the tailored coupled cluster (CC) theory in which the DMRG method is responsible for the proper description of nondynamic correlation, whereas dynamic correlation is incorporated through the framework of the CC theory. We illustrate the potential of this method on prominent multireference systems, in particular, N2 and Cr2 molecules and also oxo Mn(Salen), for which we have performed the first post-DMRG computations in order to shed light on the energy ordering of the lowest spin states. PMID- 27682625 TI - The acceptability and feasibility of using the Adult Social Care Outcomes Toolkit (ASCOT) to inform practice in care homes. AB - BACKGROUND: The Adult Social Care Outcomes Toolkit (ASCOT) measures social care related quality of life (SCRQoL) and can be used to measure outcomes and demonstrate impact across different social care settings. This exploratory study built on previous work by collecting new inter-rater reliability data on the mixed-methods version of the toolkit and exploring how it might be used to inform practice in four case study homes. METHOD: We worked with two care home providers to agree an in-depth study collecting SCRQoL data in four case-study homes. Data was collected about residents' age, ethnicity, cognitive impairment, ability to perform activities of daily living and SCRQoL in the four homes. Feedback sessions with staff and managers were held in the homes two weeks after baseline and follow-up data collected three months later. Interviews with managers explored their views of the feedback and recorded any changes that had been made because of it. RESULTS: Participant recruitment was challenging, despite working in partnership with the homes. Resident response rates ranged from 23 to 54 % with 58 residents from four care homes taking part in the research. 53 % lacked capacity to consent. Inter-rater reliability for the ASCOT ratings of SCRQoL were good at time one (IRR = 0.72) and excellent at time two (IRR = 0.76). During the study, residents' ability to perform activities of daily living declined significantly (z = -2.67, p < .01), as did their expected needs in the absence of services (z = -2.41, p < .05). Despite these rapid declines in functionings, residents' current SCRQoL declined slightly but not significantly (Z = -1.49, p = .14). Staff responded positively to the feedback given and managers reported implementing changes in practice because of it. CONCLUSION: This exploratory study faced many challenges in the recruitment of residents, many of whom were cognitively impaired. Nevertheless, without a mixed-methods approach many of the residents living in the care homes would have been excluded from the research altogether or had their views represented only by a representative or proxy. The value of the mixed-methods toolkit and its potential for use by providers is discussed. PMID- 27682627 TI - Update: Routine screening for antibodies to human immunodeficiency virus, civilian applicants for U.S. military service and U.S. Armed Forces, active and reserve components, January 2011-June 2016. AB - This report contains an update through June 2016 of the results of routine screening for antibodies to the human immunodeficiency virus (HIV) among civilian applicants for military service and among members of the active and reserve components of the U.S. Armed Forces. During the surveillance period, annual seroprevalences among civilian applicants for military service peaked in 2015 (0.31 per 1,000 tested), up 29% from 2014 (0.24 per 1,000 tested). Seroprevalences among Marine Corps reservists, Navy active component service members, and Navy reservists also peaked in 2015. In the Army National Guard and the reserve component of the Marine Corps, full-year seroprevalences have trended upward since 2011. Overall (January 2011-June 2016) seroprevalences were highest for Army reservists, Army National Guard members, Navy active component members, and Navy reservists. Among active and reserve component service members, seroprevalences continue to be higher among Army and Navy members and males than their respective counterparts. PMID- 27682628 TI - Update: Diagnoses of overweight and obesity, active component, U.S. Armed Forces, 2011-2015. AB - Excessive weight and body fat among currently serving active component members have a detrimental effect on operational effectiveness and increase the risk of both acute and chronic health effects related to overweight and obesity. During 2011-2015, the number and prevalence of active component members who received at least one clinical overweight diagnosis increased steadily (2011: n=71,168; 4.5%; 2015: n=113,958; 7.8%). Annual prevalences of clinical overweight increased most rapidly between 2011 and 2013, then remained relatively stable for the remainder of the surveillance period. Continued emphasis on improving "nutritional fitness" as well as physical fitness should continue as a priority of military medical and line leaders at every level. PMID- 27682629 TI - Update: Osteoarthritis and spondylosis, active component, U.S. Armed Forces, 2010 2015. AB - During the 6-year surveillance period, a total of 56,935 incident diagnoses of osteoarthritis (OA) and 60,968 incident diagnoses of spondylosis were identified. Age-specific rates of OA and spondylosis increased markedly with age and were higher among Army members and those in armor/motor transport occupations, compared to their respective counterparts. Among service members aged 25 years or older, the rate of OA overall was higher among black, non-Hispanic than other race/ethnicity group members, and the rate of shoulder OA was higher among males than females. Among service members aged 35 years or older, rates of OA of the knee and pelvic region/thigh were higher among females than males. Age-specific rates of spondylosis were generally higher among white, non-Hispanic than other race/ethnicity group members. Crude overall incidence rates of spondylosis were generally similar between sexes for all anatomical locations except the cervical region (20% higher for females than males). Findings suggest a need for additional research to identify military-specific equipment and activities that increase risk of acute and chronic damage to joints. PMID- 27682630 TI - Abstracts from The Academy of Breastfeeding Medicine 21(st) Annual International Meeting Washington, DC October 13-16, 2016. PMID- 27682632 TI - CORR Insights(r): What Are the Risk Factors for Dislocation of Hip Bipolar Hemiarthroplasty Through the Anterolateral Approach? A Nested Case-control Study. PMID- 27682633 TI - Thermally induced crystallization in NbO2 thin films. AB - Niobium dioxide can exhibit negative differential resistance (NDR) in metal insulator-metal (MIM) devices, which has recently attracted significant interest for its potential applications as a highly non-linear selector element in emerging nonvolatile memory (NVM) and as a locally-active element in neuromorphic circuits. In order to further understand the processing of this material system, we studied the effect of thermal annealing on a 15 nm thick NbO2 thin film sandwiched inside a nanoscale MIM device and compared it with 180 nm thick blanket NbOx (x = 2 and 2.5) films deposited on a silicon dioxide surface as references. A systematic transmission electron microscope (TEM) study revealed a similar structural transition from amorphous to a distorted rutile structure in both cases, with a transition temperature of 700 degrees C for the NbO2 inside the MIM device and a slightly higher transition temperature of 750 degrees C for the reference NbO2 film. Quantitative composition analysis from electron energy loss spectroscopy (EELS) showed the stoichiometry of the nominal 15 nm NbO2 layer in the as-fabricated MIM device deviated from the target 1:2 ratio because of an interaction with the electrode materials, which was more prominent at elevated annealing temperature. PMID- 27682634 TI - Lower serum uric acid is associated with mild cognitive impairment in early Parkinson's disease: a 4-year follow-up study. AB - Cognitive deficits are common in Parkinson's disease (PD) and many patients eventually develop dementia; however, its occurrence is unpredictable. Serum uric acid (UA) has been proposed as a biomarker of PD, both in the preclinical and clinical phase of the disease. The aim of this pilot study was to evaluate relationships between baseline serum UA levels and occurrence of mild cognitive impairment (MCI) at 4-year follow-up in a cohort of early PD patients. Early PD patients, not presenting concomitant diseases, cognitive impairment or treatment possibly interfering with UA levels, underwent neuropsychological testing at baseline and 4-year follow-up. UA levels were determined in serum at baseline. MCI was found in 23 out of 42 PD patients completing 4-year follow-up. Patients presenting MCI had significantly higher age at onset and lower Frontal Assessment Battery scores at baseline as compared with patients cognitively intact. Logistic regression analysis showed that both serum UA levels (OR = 0.54, p = 0.044) and age (OR = 1.16, p = 0.009) contribute to the occurrence of MCI at 4-year follow up. Our pilot study suggests that lower levels of serum UA in the early disease stages are associated to the later occurrence of MCI. These results need to be confirmed by further studies on larger samples. PMID- 27682636 TI - Synthesis of 6,12-Epiminodibenzo[b,f][1,5]diazocines via an Ytterbium Triflate Catalyzed, AB2 Three-Component Reaction. AB - An efficient and selective procedure for the synthesis of epiminodibenzo[b,f][1,5]diazocines involving a AB2 three-component reaction is developed. Two equivalents of suitably substituted 2-aminoarylaldehydes reacted with arylamines in the presence of Yb(OTf)3 to afford the desired products in high yields. The reaction is highly atom-economic and waste-free, in addition to allowing the generation of two heterocyclic rings and four C-N bonds in a single operation. Significantly, this approach is complementary to the existing literature procedures, affording arylamine-derived products that could not be accessed previously. A plausible mechanism is proposed involving an imine formation-intermolecular annulation-intramolecular iminium ion cyclization sequence. PMID- 27682637 TI - Primary scalp alopecia: new histopathological tools, new concepts and a practical guide to diagnosis. AB - The diagnosis of primary scalp alopecia remains one of the most challenging fields in dermatopathology. In this review, we would like to connect the established classification of primary alopecia into scarring (cicatricial) and non-scarring (non-cicatricial) with current concepts. We introduce a simplified pathway for the diagnosis of the most common causes of alopecia, including a discussion of tissue processing techniques and use of immunohistochemistry. PMID- 27682635 TI - Effects of acute doses of methylphenidate on inflammation and oxidative stress in isolated hippocampus and cerebral cortex of adult rats. AB - Methylphenidate (MPH) is a stimulatory agent in brain with unknown long-term consequences. In this study, MPH-induced neurodegeneration in adult rat brain was assessed. Rats were acutely treated with different doses of MPH. Open Field Test was used to investigate anxiety and depression levels. Inflammatory factors and anti-oxidant activity were also evaluated in isolated hippocampus and cerebral cortex. MPH treated groups (10 and 20 mg/kg) demonstrated anxiety and depression like behavior in OFT. MPH significantly increased lipid peroxidation, GSSG level, IL-1beta and TNF-alpha in isolated tissues. In addition, MPH at the same doses (10 and 20 mg/kg) reduced GSH, superoxide dismutase, glutathione peroxidase and glutathione reductase activity significantly in hippocampus and cerebral cortex. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats. PMID- 27682638 TI - Influence of temperature and relative humidity on survival and fecundity of three tsetse strains. AB - BACKGROUND: Tsetse flies occur in much of sub-Saharan Africa where they are vectors of trypanosomes that cause human and animal African trypanosomosis. The sterile insect technique (SIT) is currently used to eliminate tsetse fly populations in an area-wide integrated pest management (AW-IPM) context in Senegal and Ethiopia. Three Glossina palpalis gambiensis strains [originating from Burkina Faso (BKF), Senegal (SEN) and an introgressed strain (SENbkf)] were established and are now available for use in future AW-IPM programmes against trypanosomes in West Africa. For each strain, knowledge of the environmental survival thresholds is essential to determine which of these strains is best suited to a particular environment or ecosystem, and can therefore be used effectively in SIT programmes. METHODS: In this paper, we investigated the survival and fecundity of three G. p. gambiensis strains maintained under various conditions: 25 degrees C and 40, 50, 60, and 75 % relative humidity (rH), 30 degrees C and 60 % rH and 35 degrees C and 60 % rH. RESULTS: The survival of the three strains was dependent on temperature only, and it was unaffected by changing humidity within the tested range. The BKF strain survived temperatures above its optimum better than the SEN strain. The SENbkf showed intermediate resistance to high temperatures. A temperature of about 32 degrees C was the limit for survival for all strains. A rH ranging from 40 to 76 % had no effect on fecundity at 25-26 degrees C. CONCLUSIONS: We discuss the implications of these results on tsetse SIT-based control programmes. PMID- 27682640 TI - Highly Diastereo- and Enantioselective Cu-Catalyzed Borylative Coupling of 1,3 Dienes and Aldimines. AB - A Cu-catalyzed diastereo- and enantioselective borylative coupling reaction of 1,3-dienes with imines was realized. Branched homoallylic amines are readily prepared in a syn-selective manner with high regio-, diastereo- and enantioselectivity. Moreover, these three-component coupling reactions feature good functional-group compatibility and easy access to the substrates and catalyst. PMID- 27682639 TI - Wolf population genetics in Europe: a systematic review, meta-analysis and suggestions for conservation and management. AB - The grey wolf (Canis lupus) is an iconic large carnivore that has increasingly been recognized as an apex predator with intrinsic value and a keystone species. However, wolves have also long represented a primary source of human-carnivore conflict, which has led to long-term persecution of wolves, resulting in a significant decrease in their numbers, genetic diversity and gene flow between populations. For more effective protection and management of wolf populations in Europe, robust scientific evidence is crucial. This review serves as an analytical summary of the main findings from wolf population genetic studies in Europe, covering major studies from the 'pre-genomic era' and the first insights of the 'genomics era'. We analyse, summarize and discuss findings derived from analyses of three compartments of the mammalian genome with different inheritance modes: maternal (mitochondrial DNA), paternal (Y chromosome) and biparental [autosomal microsatellites and single nucleotide polymorphisms (SNPs)]. To describe large-scale trends and patterns of genetic variation in European wolf populations, we conducted a meta-analysis based on the results of previous microsatellite studies and also included new data, covering all 19 European countries for which wolf genetic information is available: Norway, Sweden, Finland, Estonia, Latvia, Lithuania, Poland, Czech Republic, Slovakia, Germany, Belarus, Russia, Italy, Croatia, Bulgaria, Bosnia and Herzegovina, Greece, Spain and Portugal. We compared different indices of genetic diversity in wolf populations and found a significant spatial trend in heterozygosity across Europe from south-west (lowest genetic diversity) to north-east (highest). The range of spatial autocorrelation calculated on the basis of three characteristics of genetic diversity was 650-850 km, suggesting that the genetic diversity of a given wolf population can be influenced by populations up to 850 km away. As an important outcome of this synthesis, we discuss the most pressing issues threatening wolf populations in Europe, highlight important gaps in current knowledge, suggest solutions to overcome these limitations, and provide recommendations for science-based wolf conservation and management at regional and Europe-wide scales. PMID- 27682641 TI - Occurrence of human respiratory syncytial virus in summer in Japan. AB - In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature * relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ?28.2 degrees C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present. PMID- 27682642 TI - Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection. AB - BACKGROUND: Previous RCTs have failed to demonstrate the usefulness of combining energy devices with the conventional clamp crushing method to reduce blood loss during liver transection. Here, the combination of an ultrasonically activated device (UAD) and a bipolar vessel-sealing device (BVSD) with crush clamping was investigated. METHODS: Patients scheduled to undergo hepatectomy at the University of Tokyo Hospital or Nihon University Itabashi Hospital were eligible for this parallel-group, single-blinded randomized study. Patients were assigned to a control group (no energy device used), an UAD group or a BVSD group. The primary endpoint was the volume of blood loss during liver transection. Outcomes of the control group and the combined energy device groups (UAD plus BVSD) were first compared. Pairwise comparisons among the three groups were made for outcomes for which the combined energy device group was superior to the control group. RESULTS: A total of 380 patients were enrolled between July 2012 and May 2014; 116 patients in the control group, 122 in the UAD group and 123 in the BVSD group were included in the final analysis. Median blood loss during liver transection was lower in the combined energy device group (245 patients) than in the control group (116 patients): median 190 (range 0-3575) versus 230 (range 3 1570) ml (P = 0.048). Pairwise comparison revealed that blood loss was lower in the BVSD group than in the control group (P = 0.043). CONCLUSION: The use of energy devices combined with crush clamping reduced blood loss during liver transection. Registration number: C000008372 (www.umin.ac.jp/ctr/index.htm). PMID- 27682643 TI - Infant, Control Thyself: Infants' Integration of Multiple Social Cues to Regulate Their Imitative Behavior. AB - This study investigated 15-month-old infants' (N = 150) ability to self-regulate based on observing a social interaction between two adults. Infants were bystanders to a social exchange in which an Experimenter performed actions on objects and an Emoter expressed anger, as if they were forbidden acts. Next, the Emoter became neutral and her visual access to the infant was experimentally manipulated. The Emoter either: (a) left the room, (b) turned her back, (c) faced the infant but looked down at a magazine, or (d) faced and looked toward the infant. Infants were then presented with the test objects. When the previously angry Emoter was facing them, infants were hesitant to imitate the demonstrated acts in comparison to the other conditions. We hypothesize that infants integrated the emotional and visual-perceptual cues to determine whether the Emoter would get angry at them, and then regulated their behavior accordingly. Temperament was related to infants' self-regulation -infants with higher impulsivity scores were more likely to perform the forbidden acts. Taken together, these findings provide insight into the roots of executive functions in late infancy. PMID- 27682644 TI - Editorial: Spilled Over Emerging Infectious Diseases Necessitate an Accelerated Drug Design and Discovery Program: Some Comments with Special Reference to Chemoinformatics and the Current Zika Virus Crisis. PMID- 27682645 TI - Every caesarean section must count. AB - Caesarean section rates (CSR) have climbed over the last three decades but some authors have argued that there is no reason to count them, claiming that this practice may lead to inappropriate attempts to lower CSR. However, there are many adverse effects of CS and these are short, medium and long-term for both mother and baby. There is likely to be an optimal CSR which gives the best perinatal outcomes and unless each caesarean counts, and is counted, CSR will be higher than they need to be for best perinatal outcomes. PMID- 27682646 TI - Prophylactic total gastrectomy in the management of hereditary tumor syndromes. AB - PURPOSE: Germline mutations in several genes confer a relevant lifetime risk of gastric cancer. In this context, an increasing involvement of a surgeon can be seen, mainly with the question of performing a prophylactic operation. METHODS: Patients with hereditary tumor syndromes predisposing for gastric cancer who received care leading to prophylactic total gastrectomy in our Center for Hereditary Tumor Syndromes were analyzed. For each patient, the multidisciplinary decision-making process, the perioperative course, and the histopathologic findings were assessed. Short-term morbidity was evaluated based on the medical reports. RESULTS: The analysis includes nine patients (six female, three male) with a median age of 41.6 (range 23-60) years. Indication for prophylactic total gastrectomy was based on family history and genetic analysis (eight patients with a germline mutation of the CDH1 gene and one patient with a SMAD4 mutation). Removal of the entire gastric mucosa was documented intraoperatively by fresh frozen section examination. Extended (DII) lymphadenectomy was performed in four patients. Histopathologic examination of gastrectomy specimens revealed six patients (6/9, 67 %) with multifocal signet ring cell carcinomas. In our series, prophylactic total gastrectomy was a safe procedure without mortality and low morbidity. CONCLUSIONS: Patients with hereditary syndromes predisposing for gastric cancer should be evaluated for this curative procedure in a specialized center. Further research is necessary, and the implementation of nationwide registers including patients with prophylactic gastrointestinal operations due to hereditary tumor syndrome is advisable. PMID- 27682647 TI - Ileal pouch-anal anastomosis 20 years later: is it still a good surgical option for patients with ulcerative colitis? AB - PURPOSE: Short-term results after ileo-pouch anal anastomosis (IPAA) are well established; data are conflicting in long-standing patients. We retrospectively evaluated long-term complications and functional results after follow-up longer than 20 years. METHODS: Two hundred five patients with follow-up longer than 20 years have been identified out of 1112 IPAA performed in our institution; of these, 20 cases were lost at follow-up or decline to take part at the study. We evaluated long-term complications and failure rate also according to changes in histological diagnosis. Changes in functional results and quality of life (QoL) were analyzed at 5 and 20 years after IPAA. RESULTS: Pouch failure rate was 10.8 % (35 % due to misdiagnosed Crohn). Incidences of fistulas, anastomotic stenosis, chronic pouchitis, and pre-pouch ileitis were 17.3, 12.9, 28.6, and 7.6 %, respectively. Most of the patients reported good functional outcomes. Day-time evacuations at 5 and after 20 years were 4.3 and 4.8 (p = n.s.) while during night-time were 0.8 and 1.2 (p < 0.05). Urgency was 6 and 9.4 % (p = n.s.), respectively; need of antimotility drugs was 16 and 35 % (p < 0.001). Dietary limitations and work restrictions were similar over time. Only sexuality got worse during follow-up. Satisfaction for surgery was always high and it did not change over time. CONCLUSION: IPAA is still an excellent surgical option for UC with a low rate of pouch failure even after more than 20 years. Despite a slight worsening of functional results over time, the QoL remained high and most patients expressed satisfaction with the procedure and were willing to recommend it to others. PMID- 27682648 TI - Comparative diagnostic accuracy of hepatocyte-specific gadoxetic acid (Gd-EOB DTPA) enhanced MR imaging and contrast enhanced CT for the detection of liver metastases: a systematic review and meta-analysis. AB - PURPOSE: This systematic review evaluated the diagnostic accuracy and impact on patient management of hepatocyte-specific gadoxetic acid enhanced magnetic resonance imaging (GA-MRI) compared to contrast enhanced computed tomography (CE CT) in patients with liver metastases. METHOD: Four biomedical databases (PubMed, EMBASE, Cochrane Library, York CRD) were searched from January 1991 to February 2016. Studies investigating the accuracy or management impact of GA-MRI compared to CE-CT in patients with known or suspected liver metastases were included. Bias was evaluated using QUADAS-II. Univariate meta-analysis of sensitivity ratios (RR) were conducted in the absence of heterogeneity, calculated using I 2 , Tau values (tau) and prediction intervals. RESULTS: Nine diagnostic accuracy studies (537 patients with 1216 lesions) and four change in management studies (488 patients with 281 lesions) were included. Per-lesion sensitivity and specificity estimates for GA-MRI ranged from 86.9-100.0 % and 80.2-98.0 %, respectively, compared to 51.8-84.6 % and 77.2-98.0 % for CE-CT. Meta-analysis found GA-MRI to be significantly more sensitive than CE-CT (RR = 1.29, 95 % CI = 1.18-1.40, P < 0.001), with equivalent specificity (RR = 0.97, 95 % CI 0.910-1.042, P = 0.44). The largest difference was observed for lesions smaller than 10 mm for which GA MRI was significantly more sensitive (RR = 2.21, 95 % CI = 1.47-3.32, P < 0.001) but less specific (RR = 0.92, 95 % CI 0.87-0.98, P = 0.008). GA-MRI affected clinical management in 26 of 155 patients (16.8 %) who had a prior CE-CT; however, no studies investigated the consequences of using GA-MRI instead of CE CT. CONCLUSION: GA-MRI is significantly more sensitive than CE-CT for detecting liver metastases, which leads to a modest impact on patient management in the context of an equivocal CE-CT result. PMID- 27682650 TI - Differences in the association between high blood pressure and cognitive functioning among the general Japanese population aged 70 to 80 years old: methodological issues to avoid misinterpretation. PMID- 27682649 TI - Autoantibody to scaffold attachment factor B (SAFB): A novel connective tissue disease-related autoantibody associated with interstitial lung disease. AB - OBJECTIVE: To identify and characterize a novel connective tissue disease (CTD) related autoantibody (autoAb) directed against scaffold attachment factor B (SAFB). METHODS: AutoAb specificity was analyzed using RNA and protein immunoprecipitation assays. Autoimmune targets were affinity purified using patients' sera and subjected to liquid chromatography mass spectrometry. RESULTS: By immunoprecipitation assay, 10 sera reacted with a protein with a molecular weight of approximately 160 kDa. Liquid chromatography mass spectrometry of the partially purified autoantigen and additional immunoblot-based analyses revealed that the Ab specifically recognized SAFB. Anti-SAFB Abs were detected in 2 of 646 patients with systemic sclerosis (SSc) (0.3%), 1 of 1570 patients with polymyositis/dermatomyositis (0.06%), 4 of 270 patients with interstitial lung disease (ILD) (1.5%), 1 of 43 patients with overlap syndrome (2.3%) and 2 patients with other diseases including primary Raynaud's disease and eosinophilic pneumonia. Five patients with anti-SAFB Abs had Raynaud's phenomenon and 3 had nail fold punctate hemorrhage. Of note, 8 of the 10 patients (80%) suffered from ILD. None of the patients with anti-SAFB Abs had pulmonary arterial hypertension, heart disease, or renal involvement. CONCLUSIONS: Anti-SAFB Ab is a novel CTD related autoAb possibly associated with ILD. PMID- 27682651 TI - Seasonal variation in self-measured home blood pressure among patients on antihypertensive medications: HOMED-BP study. AB - Seasonal variation of blood pressure (BP) has been reported in small populations or by BP levels captured at only a few points in a year, for example, summer and winter. We aimed to investigate the multiyear seasonal variation in self-measured home BP among hypertensive patients receiving antihypertensive medications. We selected 1649 eligible patients receiving antihypertensive drug treatment, and weekly averaged home BPs were analyzed throughout the follow-up period. Systolic and diastolic home BPs were fitted with the cosine function: 'Variation+Other Effects+Intercept', in which the 'Variation' was expressed by a cosine curve with three parameters representing: (1) maximum-minimum difference of home BP in one cycle of the cosine curve; (2) time required for one cycle of the cosine curve for home BP variation; and (3) time at which home BP reached the maximum point. Maximum-minimum differences in home BP were 6.7/2.9 mm Hg, and the highest home BPs were observed in mid-to-late January. In the multivariable-adjusted model, a large maximum-minimum difference in home BP was associated with lower body mass index and older age, and larger differences were observed in men compared with women. Summer-winter difference in home BP was essentially similar every year, though it was marginally reduced by 0.14/0.04 mm Hg per year, under long-term antihypertensive treatment. Records of daily home BP measurements enable us to capture long-term factors such as seasonal variation. Home BP should therefore be carefully monitored, particularly in patients with increased BP in winter, to mitigate cardiovascular risk. PMID- 27682652 TI - Second derivative of the finger photoplethysmogram and cardiovascular mortality in middle-aged and elderly Japanese women. AB - The second derivative of the digital photoplethysmogram (SDPTG) is an indicator of arterial stiffness. The ratio of the height of the d wave to the a wave of the SDPTG (d/a) is associated with functional peripheral vascular tension and represents aortic-blood pressure (BP) augmented by reflection waves from the periphery. This longitudinal study aimed to investigate the relationship between SDPTG and cardiovascular mortality in middle-aged and elderly Japanese women. From 1998 to 2008, we recruited 4373 women (50-79 years old at baseline) who underwent medical check-ups and SDPTG measurement. The SDPTG index (d/a) was calculated from the wave component height, and was divided into quartiles (Q) according to the d/a value. The median follow-up period was 9.0 years. The d/a value was negatively associated with age and BP, and positively associated with heart rate and body height. Using the Cox proportional hazards model, the hazard ratios for cardiovascular mortality for Q2, Q3 and Q4 were significantly higher than that of Q1. In multivariate analysis, the hazard ratio was 2.30 for Q3 (95% confidence interval (CI): 1.06-4.99, P<0.05) and 2.60 for Q4 (95% CI: 1.21-5.60, P<0.05), after adjustment for age, height, body mass index, BP levels, heart rate and other atherosclerosis-related factors. The hazard ratios of cardiovascular mortality for Q3 and Q4 were significantly higher compared with the reference (Q1). Thus, the SDPTG d/a is an independent predictor of cardiovascular mortality in middle-aged and elderly Japanese women. PMID- 27682653 TI - Use of serum fibroblast growth factor 23 vs. plasma B-type natriuretic peptide levels in assessing the pathophysiology of patients with heart failure. AB - Recently, fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone, has been linked to the pathophysiology of heart failure (HF), thus encouraging us to examine which hemodynamic abnormalities of HF are linked to either serum FGF23 or plasma B-type natriuretic peptide (BNP) levels. We measured both the serum FGF23 and plasma BNP levels in 154 consecutive prospectively enrolled hospitalized HF patients, with an estimated glomerular filtration rate >40 ml min 1 1.73 m-2, who underwent heart catheterizations and an echocardiogram. The serum FGF23 levels correlated with the diameter of the inferior vena cava and its respiratory changes, whereas the plasma BNP levels did not. Both the plasma BNP and serum FGF23 levels were moderately correlated with the mean pulmonary artery (PA) pressure and pulmonary capillary wedge (PCW) pressure. Interestingly, in patients with an above-median right-atrial (RA) pressure (4 mm Hg), FGF23 levels were correlated with both PA and PCW pressures, but the levels were not correlated in patients with a below-median RA pressure. In contrast, the plasma BNP levels were correlated with both PA and PCW pressures. Finally, serum FGF23 levels, compared with the plasma BNP levels, were more strongly associated with the clinical outcomes in patients with above-median RA pressure. These findings suggested that serum FGF23 levels are predominantly correlated with clinical outcomes, may serve as a biomarker for HF in patients with higher RA pressure, may provide beneficial information for patients with right-sided HF and may represent different clinical information than that provided only by plasma BNP levels. PMID- 27682655 TI - Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. AB - Hypertensive disorders in pregnancy (HDP) represent some of the most important problems faced by public health because HDP is a major cause of maternal and prenatal morbidity and mortality. Several epidemiological studies have been performed to determine the prevalence and risk factors of HDP as well as its subtypes. The prevalences of HDP, gestational hypertension and preeclampsia are 5.2-8.2%, 1.8-4.4% and 0.2-9.2%, respectively. Body mass index, anemia and lower education appear to be modifiable risk factors for HDP. Maternal age, primiparous, multiple pregnancy, HDP in previous pregnancy, gestational diabetes mellitus, preexisting hypertension, preexisting type 2 diabetes mellitus, preexisting urinary tract infection and a family history of hypertension, type 2 diabetes mellitus and preeclampsia appear to be nonmodifiable risk factors. Genetic variants including a single-nucleotide polymorphism in the angiotensinogen gene have also been reported to be nonmodifiable risk factors. Epidemiological studies have recently examined the associations between a history of HDP and its subtypes and future risks of other diseases. These studies have reported associations between a history of HDP and a risk of coronary heart disease, heart failure, dysrhythmia, stroke, hypertension, diabetes mellitus, end stage renal dysfunction and cardiomyopathy. HDP is not associated with the future incidence of total cancer. In conclusion, HDP is not a rare complication of pregnancy and the influence of HDP remains for an extended duration. Physicians should consider the effects of HDP when treating chronic diseases in women. PMID- 27682656 TI - Left atrial dimension is related to blood pressure variability in newly diagnosed untreated hypertensive patients: methodological and statistical issues. PMID- 27682654 TI - The association of endothelin-1 with markers of oxidative stress in a biethnic South African cohort: the SABPA study. AB - Both endothelin-1 and oxidative stress have important roles in the development of cardiovascular diseases such as hypertension and atherosclerosis. Limited information is available on the interaction between oxidative stress, the glutathione system and endothelin-1 in humans. We aimed to investigate the association of endothelin-1 with markers of oxidative stress and the antioxidant capacity in a biethnic South African cohort. This cross-sectional study included 195 black and 198 white South Africans. Serum endothelin-1 levels and oxidative stress-related markers such as reactive oxygen species (measured as serum peroxides), glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase were measured. In single, partial and multiple regression analyses endothelin-1 correlated positively with glutathione reductase activity (adj. R2=0.10; beta=0.232; P=0.020) and negatively with antihypertension medication (P=0.02) and tended to correlate with glutathione reductase-to-glutathione peroxidase ratio (adj. R2=0.10; beta=0.19; P=0.057) in black men. In white men, endothelin-1 correlated positively with ROS (adj. R2=0.09; beta=0.26; P=0.01) and negatively with glutathione peroxidase activity (adj. R2=0.05; beta=-0.23; P=0.02). In black women, endothelin-1 correlated negatively with total glutathione (adj. R2=0.22; beta=-0.214; P=0.026). Endothelin-1 may contribute to glutathione reductase upregulation through increased reactive oxygen species production mediated via endothelin-1 in black men. In white men, we observed a negative association between glutathione peroxidase and endothelin-1, describing the expected physiological relationship between endothelin-1 and reactive oxygen species. Higher total glutathione levels may act as a counter-regulatory mechanism to protect against oxidative vascular damage attributed by endothelin-1 in black women. PMID- 27682657 TI - Successful rotational atherectomy over RG3 guidewire after failure of various techniques to deliver RotaWire. AB - Although performing rotational atherectomy (RA) requires guidewire exchange for the dedicated guidewire, RotaWire guidewire (Boston Scientific) exhibits much lower performance than conventional guidewire. Consequently, there are times when RotaWire cannot be advanced past the lesion independently or using a microcatheter exchange technique, rendering RA impossible. We present a case of a heavily calcified, device-uncrossable, and non-expansible chronic total occlusion lesion successfully revascularized with RA over RG3 guidewire (Asahi Intecc), which has a length of 330 cm, hydrophilic coating, and a 0.010-inch-long shaft. RG3 provided excellent cross-ability and RA could also be performed over RG3 without guidewire exchange for the RotaWire. PMID- 27682658 TI - Stepwise Simulation of 3,5-Dihydro-5-methylidene-4H-imidazol-4-one (MIO) Biogenesis in Histidine Ammonia-lyase. AB - A 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) electrophilic moiety is post translationally and autocatalytically generated in homotetrameric histidine ammonia-lyase (HAL) and other enzymes containing the tripeptide Ala-Ser-Gly in a suitably positioned loop. The backbone cyclization step is identical to that taking place during fluorophore formation in green fluorescent protein from the tripeptide Ser-Tyr-Gly, but dehydration, rather than dehydrogenation by molecular oxygen, is the reaction that gives rise to the mature MIO ring system. To gain additional insight into this unique process and shed light on some still unresolved issues, we have made use of extensive molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics calculations implementing the self-consistent charge density functional tight-binding method on a fully solvated tetramer of Pseudomonas putida HAL. Our results strongly support the idea that mechanical compression of the reacting loop by neighboring protein residues in the precursor state is absolutely required to prevent formation of inhibitory main-chain hydrogen bonds and to enforce proper alignment of donor and acceptor orbitals for bond creation. The consideration of the protein environment in our computations shows that water molecules, which have been mostly neglected in previous theoretical work, play a highly relevant role in the reaction mechanism and, more importantly, that backbone cyclization resulting from the nucleophilic attack of the Gly amide lone pair on the pi* orbital of the Ala carbonyl precedes side-chain dehydration of the central serine. PMID- 27682659 TI - [Current status of work-related musculoskeletal disorders in nurses in Xinjiang, China]. AB - Objective: To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in nurses in Xinjiang, China, to analyze the influencing factors for the development of WMSDs, and to provide a reference for the prevention and treatment of WMSDs in nurses. Methods: Stratified cluster sampling was used to randomly select 8 422 nurses in 8 tertiary hospitals and 4 secondary hospitals in Xinjiang from January to October, 2015. A questionnaire survey was performed to investigate the prevalence of WMSDs in nurses from departments of internal medicine, surgery, gynecology, pediatrics, emergency, and intensive care and operating rooms and analyze related influencing factors. Results: A total of 3 000 questionnaires were distributed, and 2 851 questionnaires were returned, resulting in a recovery rate of 95.00%. In the nurses who participated in the survey, the prevalence of WMSDs was 78.58%. As for different body parts, the prevalence of WMSDs was 63.36% in the waist, 61.79% in the neck, 52.52% in the shoulder, 41.83% in the back, 35.56% in the knees, 33.35% in the ankles, 26.02% in the wrists, 23.41% in the hip, and 17.62% in the elbows. There were significant differences in the prevalence of WMSDs across the nurses with different ages and working years (chi2=28.29 and 27.73, both P<0.01) , and the prevalence of WMSDs tended to increase with the increasing age and working years (chi2=22.94 and 17.56, both P<0.01) . The results of multivariate logistic regression analysis showed that sex, working years, intensive care/emergency, outpatient service, surgical anesthesia, weekly working hours, physical condition, and fatigue in work were risk factors for WMSDs in nurses. Conclusion: In the nurses in Xinjiang, the prevalence of WMSDs in the neck, shoulder, back, and waist is high, and nurses with different ages, working years, departments, sexes, physical conditions, and weekly working hours have varying degrees of risk of WMSDs. PMID- 27682660 TI - [An investigation of the application of hygienic standards for the design of industrial enterprises (GBZ 1-2010)]. AB - Objective: To study the applicability, the high frequency used content, the feasibility, and issues needed to be solved of the standard of GBZ 1-2010, aiming to provide technical evidence for the revision of GBZ1. Methods: In the study, the data were collected by referring to the literature database and the questionnaire from June 2013 to June 2015. There were 2 surveys carried out in the study, with methods including questionnaire survey and specific interview. The investigation methods include the paper version of the questionnaire by mail, the electronic version of the questionnaire by e-mail, and the online survey. And 111 questionnaires were collected. Results: In total, the applicability survey (the first survey) received 156 suggestions covering 76 items from 23 facilities, and 13 key technical issues were summarized to be solved as priorities. In the application survey (the second survey) , the leading three jobs using GBZ 1-2010 were the occupational hazards evaluation for constructive project (82.0%) , lecturing/training (65.8%) , occupational hazards monitoring (64.9%) , respectively. The high frequency used contents of GBZ 1-2010 were the sixth part "the basic hygienic requirements for workplace" (90.1%) , the fifth part "site selection, overall layout and workshop design" (87.4%) , the seventh part "the basic hygienic requirements for welfare room" (85.6%) , respectively. In the results of feasibility, scores of the fourth part "the general rules" , the fifth part "site selection, overall layout and workshop design" , the sixth part "the basic hygienic requirements for workplace" , the seventh part "the basic hygienic requirements for welfare room" , the eighth "emergency rescue" , annex A "the correct use instructions" , annex B "buffer zone standards for industrial enterprises" were 2.6, 3.1, 3.5, 3.8, 3.2, 3.3, 2.6, respectively. Among 111 questionnaires, the parts needed to be modified as priories were the fifth part "site selection, overall layout and workshop design" (51.4%) , and the sixth part "the basic hygienic requirements for workplace" (51.4%) . In results of the key technical issues needed to be modified of GBZ 1-2010, the contents needed to be added as priories were the occupational prevention and control requirements of biological factors (51.4%) , technical parameters of dust in workplace (48.7%) , technical parameters of hazardous agents in workplace (46.9%) , the quality and quantity requirements of fresh air (46.0%) , the setting conditions of the emergency rescue station (46.0%) , the hygienic design requirements of joint workshops and the evidence (45.1%) , and requirements for medical emergency rescue personnel equipped and qualified (45.1%) . Conclusion: GBZ 1-2010 is feasible and practical, mainly used by occupational health technical service organizations in the occupational hazards evaluation for constructive project, lecturing/training, occupational hazards monitoring, et al. GBZ 1 plays a directive role in government decision-making, control of constructive projects from the beginning, training and capacity building of occupational health professionals, and the prevention and treatment of occupational diseases in enterprises, needing to strengthen the implementation of GBZ 1. And on the basis of the above key technical issues to be revised, international cooperation and exchanges should be strengthened, so that it is adapted to the development of the modern enterprise system. PMID- 27682661 TI - [Association between musculoskeletal disorders in the lower limbs and occupational stress in bus drivers]. AB - Objective: To investigate the prevalence of work-related musculoskeletal disorders (MSDs) in the lower limbs and occupational stress in bus drivers, as well as the association between occupational stress and MSDs in the lower limbs, and to provide a reference for the prevention and control of MSDs in the lower limbs in bus drivers. Methods: Cluster sampling was used to collect 598 bus drivers from those who underwent physical examination in a hospital in Chengdu, China, from June to July, 2015. The data on demographic features and living habits were collected, and the Chinese version of effort-reward imbalance questionnaire and Nordic Standardized Questionnaires for Musculoskeletal Disorders were used to investigate occupational stress and the development of MSDs. Results: In these bus drivers, the prevalence of MSDs in the lower limbs was 51.2%, and that in the thigh/hip, ankle/foot, and knee was 36.8%, 32.2%, and 31.4%, respectively. The multivariate regression analysis showed that effort reward imbalance was the risk factor for MSDs in the lower limbs, and the OR values for the lower limbs, thigh/hip, knee, and ankle/foot were 3.96 (95% CI: 2.19~7.18) , 3.86 (95% CI: 2.05~7.28) , 2.47 (95% CI: 1.30~4.70) , and 2.45 (95% CI: 1.32~4.56) , respectively. Conclusion: Occupational stress is associated with an increased risk of MSDs in the lower limbs in bus drivers. PMID- 27682662 TI - [Application of three risk assessment models in occupational health risk assessment of dimethylformamide]. AB - Objective: To investigate the application of United States Environmental Protection Agency (EPA) inhalation risk assessment model, Singapore semi quantitative risk assessment model, and occupational hazards risk assessment index method in occupational health risk in enterprises using dimethylformamide (DMF) in a certain area in Jiangsu, China, and to put forward related risk control measures. Methods: The industries involving DMF exposure in Jiangsu province were chosen as the evaluation objects in 2013 and three risk assessment models were used in the evaluation. EPA inhalation risk assessment model: HQ=EC/RfC; Singapore semi-quantitative risk assessment model: Risk= (HR*ER) 1/2; Occupational hazards risk assessment index=2Health effect level*2exposure ratio*Operation condition level. Results: The results of hazard quotient (HQ>1) from EPA inhalation risk assessment model suggested that all the workshops (dry method, wet method and printing) and work positions (pasting, burdening, unreeling, rolling, assisting) were high risk. The results of Singapore semi quantitative risk assessment model indicated that the workshop risk level of dry method, wet method and printing were 3.5 (high) , 3.5 (high) and 2.8 (general) , and position risk level of pasting, burdening, unreeling, rolling, assisting were 4 (high) , 4 (high) , 2.8 (general) , 2.8 (general) and 2.8 (general) . The results of occupational hazards risk assessment index method demonstrated that the position risk index of pasting, burdening, unreeling, rolling, assisting were 42 (high) , 33 (high) , 23 (middle) , 21 (middle) and 22 (middle) . The results of Singapore semi-quantitative risk assessment model and occupational hazards risk assessment index method were similar, while EPA inhalation risk assessment model indicated all the workshops and positions were high risk. Conclusion: The occupational hazards risk assessment index method fully considers health effects, exposure, and operating conditions and can comprehensively and accurately evaluate occupational health risk caused by DMF. PMID- 27682663 TI - [HSP70 gene polymorphism on genetic susceptibility to the coal worker's penumoconiosis of han nationality in Xinjiang, China.] AB - Objective: To explore the influence of heat shock protein 70 (HSP70) gene genetic susceptibility of coal worker's pneumoconiosis among the han nationality in xinjiang. Methods: 156 coal worker's pneumoconiosis patients and 96 mine workers were randomly selected from the han coal worker's pneumoconiosis patients and attend the health check retirement mine workers from March to December, 2014 in Xinjiang Uygur Autonomous Region of Occupational Disease Hospital. Using TaqMan genotyping methods to detect HSP70 genotype distribution in the two groups. Results: The HSP70-1+190 loci GC genotype occurrence frequencies of coal worker's pneumoconiosis was significantly higher than the control group (chi2=6.75, P<0.05) , the risk of coal worker's pneumoconiosis armed with HSP70-1+190 GC genotype individual was 2.21 times of CC genotype individual (95%CI: 1.03~4.75) , and HSP70-2+1267 and HSP70-hom+2437 loci polymorphism were no significant difference between the two groups (HSP70-2+1267: chi2=3.30, P=0.19; HSP70 hom+2437: chi2=0.12, P=0.94) . Conclusion: HSP70-1+190 GC genotypes may be a susceptible genotype, the genotype individual may be more likely to suffer from coal worker's pneumoconiosis. PMID- 27682664 TI - [A survey of current status of noise hazard on offshore oil platforms]. AB - Objective: To investigate the noise distribution characteristics, workers' exposure to noise, and protective measures against noise on offshore oil platforms. Methods: Six offshore oil platforms with a similar scale of production from China National Offshore Oil Corporation were selected from June to October, 2015 to conduct a field investigation of occupational health and detection of risk factors for occupational diseases and to know the current status of noise hazard on offshore oil platforms. Results: Among the 373 sites for noise measurement, 69.7% had a noise level of >=80 dB (A) ; among the 196 sites for noise measurement in the area with noisy equipment, 86.7% had a noise level of >=80 dB (A) ; among the 177 sites for noise measurement in the area without noisy equipment, 50.8% had a noise level of >=80 dB (A) . The actual sound attenuation of earplugs used on platforms was 18.6 dB (A) , and if they were worn correctly, they had a maximum value of noise protection of 103.6 dB (A) . The workers engaged in indoor operation were exposed to noise for 0.5~1.0 hour per day, and the 40 h/week equivalent sound level (weekly noise exposure, LEX, w) met the requirements in GBZ 2.2-2007 Occupational exposure limits for hazardous agents in the workplace Part 2: Physical agents[85 dB (A) ]. The workers engaged in outdoor operation were exposed to noise for 6.0~8.0 hours per day, and the over-standard rate of LEX, w was 53.7%. The noise exposure level showed a significant difference between the two groups, and indoor operation workers had a significantly lower noise exposure level than outdoor operation workers[ (69.8+/ 3.4) dB (A) vs (85.5+/-3.5) dB (A) , P<0.05]. Conclusion: Noise sources on offshore oil platforms show the characteristic of centralized distribution, and noisy equipment have a great impact on the area without noisy equipment. The noise exposure level differs significantly between workers engaged in indoor and outdoor operation, and noise protection mainly relies on personal protective supplies. PMID- 27682665 TI - [An epidemiological study of occupational injuries in Xuzhou railway from 1975 to 2015]. AB - Objective: To investigate the epidemiological characteristics of occupational injuries in Xuzhou Railway, and to provide a scientific basis for the management of railway occupational safety and hygiene. Methods: From January to March, 2016, it was used the descriptive epidemiology research methods to collect the files of the professional injuries cases reported in Xuzhou railway from 1975 to 2015 to retrospectively survey and study and analyze the characteristics of professional injuries in the aspect of sociology, time, work, damage type and nature, etc. Results: From 1975 to 2015, the number of people in Xuzhou railway who had professional injuries, reached injure level and professionally died are 804, 558 and 4. The rate of occupational injuries was 0.070/00~5.870/00 and the occupational injuries rate of up to grade was 0.030/00~1.500/00. The annual average incidence rate was 0.790/00 and the annual average incidence rate of up to grade was 0.550/00. The mortality of occupational injuries was 3.95*10-30/00. The occurrence rate of occupational injuries showed a downward trend in wave mode. The proportion of occupational injuries of 26 to 30 years old and 11 to 15 working years workers was higher, respectively, 18.03% and 19.28%. The proportion of male occupational injuries (88.56%) was higher than that of female (11.44%) . The proportion of workers with low cultural level was higher. The time period of occupational injury was more concentrated in 2: 00~3: 00 and 16: 00~17: 00, and the proportion of occupational injuries was higher in August and the first quarter. The difference in occupational injuries rates of different years had the statistical significance (chi2=6 546.121, P=0.000) . The difference in the occupational injuries rates of up to grade of different years had the statistical significance (chi2=1 981.623, P=0.000) . The mainly departments and posts involved in occupational injuries were locomotive department (26.12%) and shunting operation (25.00%) . The most kinds was vehicles injury (37.31%) and most injury parts was upper limb (34.87%) . Fracture was the most common injure nature (46.89%) . The mild degree of injury was main injury degree (72.95%) . The main reasons causing occupational injuries were violations (47.64%) and weak safety awareness (28.36%) . Conclusion: The incidence of occupational injuries in Xuzhou railway shows a trend of wave-like reduction year by year. Violations and weak awareness of safety are the main reasons for the occurrence of occupational injuries. The departments in charge of railway occupational safety and hygiene management need to take effective measures to strengthen the intervention of occupational injuries in key positions and reduce or eliminate railway occupational injuries. PMID- 27682667 TI - [Comparison of the hearing assessment results between the new diagnosis of occupational noise-induced deafness and the old one]. PMID- 27682666 TI - [An investigation of mental health in migrant workers in an enterprise]. AB - Objective: To investigate the mental health status in migrant workers in a labor intensive enterprise and related influencing factors. Methods: Typical sampling was used to perform an investigation in 910 migrant workers in a large foreign funded labor-intensive enterprise in Shenzhen, China. All the respondents gave informed consent and completed the questionnaire independently and anonymously. The self-reported mental health status was evaluated using the Beck Anxiety Inventory, Beck Depression Inventory, and General Health Questionnaire. Results: Of all the migrant workers in this enterprise, 7.2% had a positive self-reported anxiety symptom, 25.4% had a moderate or severe self-reported depression symptom, and 76.4% had a poor self-reported general health status. Age had significant influence on the self-reported depression symptom (chi2=21.968, P<0.05) ; age did not have significant influence on the self-reported anxiety and general health status (chi2=6.616,12.498, both P>0.05) . The knowledge of occupational hazards had significant influence on mental health status (chi2Depression=47.289, chi2General health=21.087, both P<0.05) . The feeling of work had significant influence on self-reported depression and general health status (chi2Depression=52.406, chi2General health=17.327, both P<0.05) . Attention to self mental health had significant influence on self-reported depression (chi2=17.714, P<0.05) , and whether the person wanted to learn the knowledge of mental health had significant influence on self-reported anxiety (chi2= 6.145, P<0.05) . Conclusion: The self-reported mental health status in migrant workers is poor and is associated with age, worry about exposure to occupational hazard factors, emphasis on mental health knowledge, and a focus on personal mental health. Therefore, targeted occupational health education and occupational mental health education should be strengthened. PMID- 27682668 TI - [An investigation of prevalence of occupational diseases and treatment implementation in migrant workers in Hunan, China]. AB - Objective: To investigate the prevalence of occupational diseases and treatment implementation in migrant workers in Hunan, China, and to provide a scientific basis for related departments to develop preventive and treatment measures and social security system for migrant workers. Methods: A retrospective investigation was performed in 2015 to collect the information of occupational diseases in migrant workers, and age, type of work, type of occupational disease, and implementation of employment injury insurance for occupation diseases were analyzed. Results: The migrant workers with occupational diseases accounted for 50.43% (11 280/22 368) of all patients with occupational diseases in Hunan, among whom 99.4% (11 212/11 280) were male workers. The mean age of migrant workers with occupational diseases was 55 years. The types of occupational diseases involved 6 categories such as occupational pneumoconiosis and occupational skin diseases, totaling 42 legal occupational diseases; 98.31% of all migrant workers (11 089/11 280) had occupational pneumoconiosis. The main types of work were underground coal miners (62.42%) , heading drivers (29.79%) , and haulage workers (2.20%) in coal mines and non-coal mines. A total of 27.25% migrant workers with occupational diseases (2 072/7 605) enjoyed employment injury insurance, and 20.84% (1 585/7 605) did not receive any medical or life compensations. Conclusion: The occupational diseases in migrant workers in Hunan are mainly pneumoconiosis, and a large proportion of those with occupational diseases do not enjoy implementation of treatment. Coal mines and non-coal mines are the high risk areas for occupational diseases in migrant workers and should be the focus of prevention and control. PMID- 27682669 TI - [Trimethyltin chloride intoxication in China: a systematic review and meta analysis]. PMID- 27682670 TI - [Skin sensitization of 3, 4-bis (4'-aminofurazano-3') furoxan in mice evaluated by BrdU-ELISA local lymph node assay]. AB - Objective: To investigate skin sensitization of 3, 4-bis (4'-aminofurazano-3') furoxan (DATF) in mice using 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA) . Methods: A total of 30 specific pathogen-free BALB/C mice were randomly divided into high-, medium-, and low-dose DATF groups, positive control group, and solvent control group, with six mice in each group. The mice in the high-, medium-, and low-dose DATF groups were treated with 50%, 25%, and 10% (0.5, 0.25, and 0.10 g/ml) DATF solution, those in the positive control group were treated with 1% 2, 4-dinitrochlorobenzol (DNCB) , and those in the solvent control group were treated with acetone/olive oil (4?1) . After treatment, retroauricular lymph nodes were collected and cell suspension was prepared. ELISA was used to measure the level of cell proliferation after the addition of 5-bromo 2'-deoxyuridine (BrdU) , and the BrdU labeling index (LI) and test substance concentration at a stimulation index (SI) of 1.6 (EC1.6) were calculated. Results: There were no significant differences in auricular thickness between groups (P>0.05) , and DAFT did not have skin irritation. Compared with the solvent control group, the high-dose DATF group and the positive control group showed significant increases in the weight of lymph nodes (P<0.05) . Compared with the solvent control group, all the other groups showed significant increases in BrdU LI (P<0.01) . The low-, medium-, and high-dose DATF groups had SIs of 6.1, 8.8, and 12.1, respectively, and the EC1.6 of DATF was 2.2%, which suggested that DATF had strong sensitization. Conclusion: DATF has strong skin sensitization in mice, with reference to the guideline of Organization for Economic Co-operation and Development Item No. 442B (OECD TG 442B) . PMID- 27682671 TI - [Carpal canal ultrasound examination in patients with mild hand-arm vibration disease]. AB - Objective: To investigate the clinical value of ultrasound examination of carpal canal structure in patients with mild hand-arm vibration disease. Methods: A total of 29 patients (58 wrists) with mild hand-arm vibration disease who were treated in Shenzhen Prevention and Treatment Center for Occupational Diseases from May to December, 2015 were enrolled as observation group, and 20 healthy volunteers (40 wrists) were enrolled as the control group. Color Doppler ultrasound was used to observe the morphology and echo of the median nerve in the carpal canal and 9 muscle tendons and transverse carpal ligament. The thickness of transverse carpal ligament and diameter of the median nerve at the level of the hamulus of hamate bone were measured, as well as the cross-sectional area of the median nerve at the level of pisiform bone. Results: In the 29 patients with hand-arm vibration disease patients in the observation group, 8 experienced entrapment of the median nerve in the carpal canal, among whom 5 had entrapment in both wrists; there were 13 wrists (23%) with nerve entrapment and 45 wrists (77%) without nerve entrapment. Compared with the control group, the patients with hand-arm vibration disease and nerve entrapment in the observation group showed significant thickening of the transverse carpal ligament at the level of the hamulus of hamate bone and a significant increase in the cross-sectional area of the median nerve at the level of pisiform bone (P<0.05) , while there were no significant differences in the thickness of transverse carpal ligament at the level of the hamulus of hamate bone and the cross-sectional area of the median nerve at the level of pisiform bone (t=-9.397 and -4.385, both P>0.05) . Conclusion: Ultrasound examination can clearly show the radiological changes of carpal canal contents in patients with mild hand-arm vibration disease and has a certain diagnostic value in nerve damage in patients with hand-arm vibration disease. PMID- 27682672 TI - [An analysis on two cases of occupational brucellosis]. PMID- 27682673 TI - [Determination of tert-butyl alcohol in the air of the workplace by solvent desorption gas chromatography]. AB - Objective: To establish solvent desorption gas chromatographic method for determination of tert-butyl alcohol in the air of the workplace. Methods: After tert-butyl alcohol in the air of the workplace collected with activated carbon tube and desorbed with 2% 2-propanol in CS2, and then separated with DB-FFAP capillary column and detected with flame ionization detector. Results: The linearity ranges were 0.6~2 264.0 mg/L. The limit of quantification was 0.6 mg/L. The determination has a good reproducibility. The intraassay and interassay precisions were 2.8%~3.2% and 3.8%~5.7%. The desorption efficiencies were 93.9%~98.1%. Absorption efficiencies were 95.8%~100.0%. The breakthrough volume was above 7.1 mg in 100mg activated carbon. The samples in activated carbon tube could be stored for at least 14 days at ambient temperature. Conclusion: The method is feasible for determination of tert-butyl alcohol in the air of the workplace. PMID- 27682674 TI - [An investigation of ionizing radiation dose in a manufacturing enterprise of ion absorbing type rare earth ore]. AB - Objective: To investigate radioactive source term dose monitoring and estimation results in a manufacturing enterprise of ion-absorbing type rare earth ore and the possible ionizing radiation dose received by its workers. Methods: Ionizing radiation monitoring data of the posts in the control area and supervised area of workplace were collected, and the annual average effective dose directly estimated or estimated using formulas was evaluated and analyzed. Results: In the control area and supervised area of the workplace for this rare earth ore, alpha surface contamination activity had a maximum value of 0.35 Bq/cm2 and a minimum value of 0.01 Bq/cm2; beta radioactive surface contamination activity had a maximum value of 18.8 Bq/cm2 and a minimum value of 0.22 Bq/cm2. In 14 monitoring points in the workplace, the maximum value of the annual average effective dose of occupational exposure was 1.641 mSv/a, which did not exceed the authorized limit for workers (5 mSv/a) , but exceeded the authorized limit for general personnel (0.25 mSv/a) . The radionuclide specific activity of ionic mixed rare earth oxides was determined to be 0.9. Conclusion: The annual average effective dose of occupational exposure in this enterprise does not exceed the authorized limit for workers, but it exceeds the authorized limit for general personnel. We should pay attention to the focus of the radiation process, especially for public works radiation. PMID- 27682676 TI - [DRGs and standardization management of the occupational disease list and coding]. PMID- 27682675 TI - [Evaluation on the effect of dust control facilities in a stone processing factory]. PMID- 27682677 TI - [A case of acetone burn]. PMID- 27682678 TI - [Current progress and prospect in effects of PM2.5 on metabolic syndrome]. PMID- 27682679 TI - [Current status of health protection zone standards for industrial enterprises by noise]. PMID- 27682680 TI - 6-Hydroxydopamine Inhibits the Hepatitis C Virus through Alkylation of Host and Viral Proteins and the Induction of Oxidative Stress. AB - Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintricarboxylic acid (ATA), to examine their effects on viral replication. We found that 6-OHDA inhibited HCV replication; however, 6-OHDA was a less potent inhibitor of RISC than either SUR or ATA. By generating a novel chemical probe (6 OHDA-yne), we determined that 6-OHDA covalently modifies host and virus proteins. Moreover, 6-OHDA was shown to be an alkylating agent that is capable of generating adducts with a number of enzymes involved in the oxidative stress response. Furthermore, modification of viral enzymes with 6-OHDA and 6-OHDA-yne was found to inhibit their enzymatic activity. Our findings suggest that 6-OHDA is a probe for oxidative stress as well as protein alkylation, and these properties together contribute to the antiviral effects of this compound. PMID- 27682681 TI - Evidence of a Nitrene Tunneling Reaction: Spontaneous Rearrangement of 2-Formyl Phenylnitrene to an Imino Ketene in Low-Temperature Matrixes. AB - Triplet 2-formyl phenylnitrene was generated by photolysis of 2-formyl phenylazide isolated in Ar, Kr, and Xe matrixes and characterized by IR, UV-vis, and EPR spectroscopies. Upon generation at 10 K, the triplet nitrene spontaneously rearranges in the dark to singlet 6-imino-2,4-cyclohexadien-1 ketene on the time scale of several hours. The intramolecular [1,4] H atom shift from the nitrene to the imino ketene occurs by tunneling, on the triplet manifold, followed by intersystem crossing. This case constitutes the first direct evidence of a tunneling reaction involving a nitrene. PMID- 27682683 TI - Track B. Biomechanics and Orthopaedics. PMID- 27682682 TI - Track A. Biomaterials and Biocompatibility. PMID- 27682684 TI - Track C. Biomedical Instrumentation & Micro and Nano Systems. PMID- 27682685 TI - Track E. Bioprinting and Additive Manufacturing. PMID- 27682686 TI - Track F. Biosensors and Bioanalytics. PMID- 27682687 TI - Track G. Neural Signal Processing. PMID- 27682688 TI - Track H. Cardio Technology. PMID- 27682689 TI - Track I. Cellular-, Tissue- and Bioengineering. PMID- 27682691 TI - Track K. AIIC - Developments in clinical engineering in Europe. PMID- 27682690 TI - Track J. Clinical Engineering and Hospital Technology. PMID- 27682692 TI - Track L. Devices and Systems for Surgical lntervention. PMID- 27682693 TI - Track M. Drug Delivery Technology. PMID- 27682694 TI - Track N. Functional Electrical Stimulation and Neuroprostheses. PMID- 27682695 TI - Track O. Image Computing. PMID- 27682696 TI - Track P. Medical Implants / Implant Development. PMID- 27682697 TI - Track Q. Interoperabilitat fur eine einrichtungsubergreifende Patientenversorgung. PMID- 27682698 TI - Track R. Medical Device Management. PMID- 27682699 TI - Track S. Innovationmanagement in Medical Engineering & Scientific Writing. PMID- 27682700 TI - Track T. Modelling and Simulation - Cardio Technology. PMID- 27682701 TI - Track U. BrainLinks-BrainTools-Methods and tools for neural engineering. PMID- 27682702 TI - Track V. Patient Monitoring. PMID- 27682703 TI - Track W. Personalized Health. PMID- 27682704 TI - Track X. Prosthetics and Rehabilitation Engineering. PMID- 27682705 TI - Track Y. Smart Assistance Systems. PMID- 27682706 TI - Track Z. Training and Further Education for Engineers and Physicians. PMID- 27682707 TI - Severe malnutrition causing superior mesenteric artery syndrome in an adolescent with Triple A syndrome. AB - Triple A syndrome, formerly known as Allgrove syndrome (AS), is characterized by achalasia, alacrima and adrenal insufficiency. Here we report an adolescent male with adrenal insufficiency who developed severe malnutrition secondary to a delayed diagnosis of achalasia. The severe malnutrition in our patient led to superior mesenteric artery (SMA) obstruction syndrome. Severe malnutrition to the point of SMA syndrome has not been previously described in the literature in Triple A syndrome. PMID- 27682708 TI - The outcome of seven patients with hereditary tyrosinemia type 1. AB - BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is a rare, inborn error of tyrosine metabolism. It is a fatal disorder without treatment. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival. The aim of the present study is to describe the clinical, biochemical, imaging and follow-up of seven patients with HT1 and to define the consequences of the late and interrupted treatment. METHODS: A retrospective study was carried out with seven HT1 patients. RESULTS: The median age at onset of clinical symptoms was 11.2 months (range, 3-28 months) and the median age at diagnosis was 22 months (range, 6-58 months). Liver enzymes and coagulation parameters were back to normal in all symptomatic patients in about 2 weeks. Alfa-fetoprotein (AFP) levels were normalized within the first year of therapy. Hypoechoic nodule formation was detected in two of the seven patients despite drug treatment without an increase of AFP and any dysplastic changes in the biopsies. One patient died due to metastatic HCC because of the late diagnosis and the poor compliance of the follow-up. CONCLUSIONS: This study showed once again that adherence to the treatment and a follow-up schedule of the patients are very important. Also it should not be forgotten that nodule formation can occur despite nitisinone treatment without an increase of AFP. Despite nitisinone treatment, HT1 patients still carry the risk of HCC. HCC must be detected before metastasis to other organs otherwise, patients may lose the chance for liver transplantation. PMID- 27682709 TI - Endoglin and obestatin levels, cardiometabolic risk factors and subclinical atherosclerosis in children aged 10-18 years. AB - BACKGROUND: The aim of this study was to investigate the early signs of atherosclerosis and to evaluate serum endoglin and obestatin levels as predictors of subclinical atherosclerosis in obese children. METHODS: A total of 95 children (60 obese and 35 controls) aged 10-18 years were included in the study. Their endoglin and obestatin levels and biochemical parameters were measured. The carotid intima media thickness (cIMT) and brachial artery flow-mediated dilatation (FMD) responses were evaluated. RESULTS: The cIMT values were higher (p < 0.001) and FMD responses were lower (p = 0.003) in the obese group than in the control group. A logistic regression multivariate analysis revealed that cIMT was independently associated with the body mass index (BMI) Z-score (beta = 0.323, p = 0.003) and low density lipoprotein (LDL) (beta = 0.29, p = 0.008), while FMD % was independently associated with waist circumference (beta = -0.36, p = 0.002). The obese and control groups were similar in endoglin (p = 0.67) and obestatin levels (p = 0.70). The endoglin level was inversely correlated with the cholesterol and LDL levels (r = -0.23, p = 0.032; rho = -0.25, p = 0.019). CONCLUSIONS: The cIMT and brachial artery FMD response in obese children are significantly different compared to healthy controls. Circulating endoglin and obestatin levels are not predictive markers for subclinical atherosclerosis in obese children aged 10-18 years old. PMID- 27682710 TI - Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity. AB - Most inborn errors of metabolism (IEMs) are inherited in an autosomal recessive manner. IEMs are one of the major concerns in Iran due to its extensive consanguineous marriages. Herein, we report two patients with two co-existent IEMs: a girl affected by classic phenylketonuria (PKU) and maple syrup urine disease (MSUD) and a male patient affected with Sandhoff disease and PKU, where Sandhoff disease was suspected due to the presence of a cherry-red spot in the eyes at 6 months which is unrelated to PKU. Sequencing of candidate genes in the first patient revealed one novel and three recurrent compound heterozygous mutations of p.Ser231Pro and p.Ala300Ser in the PAH gene and p.Glu330Lys and p.Arg170Cys mutations in the BCKDHB gene. Genetic testing results in the second patient showed previously reported homozygous mutations of p.Arg261Gln in the PAH and p.Arg533Cys mutation in the HEXB gene. Genetic testing confirmed the clinical diagnosis of both diseases in both patients. To the best of our knowledge; this is the first report of the co-existence of two distinct genetic disorders in two individuals from Iran. Co-existent different IEMs in patients complicated the clinical diagnosis and management of the diseases. PMID- 27682711 TI - Genetic characteristics and long-term follow-up of 11 patients with congenital hyperinsulinism followed in a single center. AB - BACKGROUND: Congenital hyperinsulinism (CHI) is a rare disease with an estimated incidence of 1:40,000 live births. Here, we characterize 11 patients treated at Munich Children's Hospital Schwabing. METHODS: We analyzed data on birth, treatment and laboratory results including genetic testing and evaluated the long term course with a follow-up visit. RESULTS: All patients had severe, diazoxide (DZX)-resistant hypoglycemia, beginning immediately after birth. Two patients were treated by medical therapy, eight underwent subtotal pancreatectomy and one had a partial resection. Both patients who had medical therapy still suffer from occasional hypoglycemia. Six patients with subtotal pancreatectomy were affected by mild hypoglycemia. Seventy-five percent of patients who had surgical treatment developed diabetes mellitus (DM) at a median age of 10.5 (8-13) years. In 89% of patients with available genetic testing, mutations of the ABCC8 gene were detected. CONCLUSIONS: The majority of CHI-patients not responding to DZX underwent surgery. After subtotal pancreatectomy, patients typically developed diabetes around early puberty. PMID- 27682712 TI - An update on thyroid-associated ophthalmopathy in children and adolescents. AB - BACKGROUND: Risk of developing thyroid-associated ophthalmopathy (TAO) in children and adolescents is similar or may be even slightly higher than in adults. The aim of this article is to review and summarize current knowledge regarding diagnostic and therapeutic measures in pediatric TAO. CONTENT: MEDLINE and EMBASE papers were searched using the terms 'pediatric Graves' ophthalmopathy' 'pediatric Graves' orbitopathy', 'thyroid-associated ophthalmopathy in childhood and adolescence' from the year 1970 to December 2015. SUMMARY: TAO usually accompanies hyperthyreosis in Graves' disease, but may also occur in patients with hypothyreosis due to chronic lymphocytic thyroiditis (Hashimoto's disease) or in euthyroid patients. Current information regarding epidemiology, pathogenesis, symptoms and treatment of TAO in children and adolescents is presented. The course of the disease is usually mild, eye disturbances often regress after restoring euthyroidism and a 'wait and see' policy is appropriate in the majority of patients. In rare cases, sight threatening complications [dysthyroid optic neuropathy (DON) or corneal breakdown] may develop and immediate surgical intervention might become necessary. OUTLOOK: Close cooperation between pediatric endocrinologists and opthalmologists is extremely important to ensure best care and quality of life in patients with thyroid gland dysfunction. Further investigations on pathogenesis and course of TAO in children and adolescents should be performed for better management of this disease in this group of patients. PMID- 27682713 TI - A FACS-based screening strategy to assess sequence-specific RNA-binding of Pumilio protein variants in E. coli. AB - Sequence-specific and programmable binding of proteins to RNA bears the potential to detect and manipulate target RNAs. Applications include analysis of subcellular RNA localization or post-transcriptional regulation but require sequence-specificity to be readily adjustable to any target RNA. The Pumilio homology domain binds an eight nucleotide target sequence in a predictable manner allowing for rational design of variants with new specificities. We describe a high-throughput system for screening Pumilio variants based on fluorescence activated cell sorting of E. coli. Our approach should help optimizing variants obtained from rational design regarding folding and stability or identifying new variants with alternative binding modes. PMID- 27682714 TI - Diagnostics for assessing the linear noise and moment closure approximations. AB - Solving the chemical master equation exactly is typically not possible, so instead we must rely on simulation based methods. Unfortunately, drawing exact realisations, results in simulating every reaction that occurs. This will preclude the use of exact simulators for models of any realistic size and so approximate algorithms become important. In this paper we describe a general framework for assessing the accuracy of the linear noise and two moment approximations. By constructing an efficient space filling design over the parameter region of interest, we present a number of useful diagnostic tools that aids modellers in assessing whether the approximation is suitable. In particular, we leverage the normality assumption of the linear noise and moment closure approximations. PMID- 27682715 TI - Accounting for isotopic clustering in Fourier transform mass spectrometry data analysis for clinical diagnostic studies. AB - Mass spectrometry based clinical proteomics has emerged as a powerful tool for high-throughput protein profiling and biomarker discovery. Recent improvements in mass spectrometry technology have boosted the potential of proteomic studies in biomedical research. However, the complexity of the proteomic expression introduces new statistical challenges in summarizing and analyzing the acquired data. Statistical methods for optimally processing proteomic data are currently a growing field of research. In this paper we present simple, yet appropriate methods to preprocess, summarize and analyze high-throughput MALDI-FTICR mass spectrometry data, collected in a case-control fashion, while dealing with the statistical challenges that accompany such data. The known statistical properties of the isotopic distribution of the peptide molecules are used to preprocess the spectra and translate the proteomic expression into a condensed data set. Information on either the intensity level or the shape of the identified isotopic clusters is used to derive summary measures on which diagnostic rules for disease status allocation will be based. Results indicate that both the shape of the identified isotopic clusters and the overall intensity level carry information on the class outcome and can be used to predict the presence or absence of the disease. PMID- 27682716 TI - Alleviation of 5-fluorouracil-induced intestinal mucositis in rats by vitamin E via targeting oxidative stress and inflammatory markers. AB - BackgroundIntestinal mucositis is a major concern related with cancer therapy. It is well established that overproduction of reactive oxygen species and inflammatory mediators plays vital role in the pathogenesis of mucositis. The aim of the study was to investigate the modulatory effect of vitamin E (vit. E) on 5 fluorouracil (5-FU)-induced intestinal mucositis by targeting oxidative stress and inflammatory markers in rats. MethodsRats were randomly divided into four groups of six animals each. All four-group animals received normal standard diet and water throughout the experimental period which last up to 10 days. Rats were gavaged with vit. E (300 mg/kg b. wt.) daily for 10 days (day 1-10) and were given intraperitoneal injection of 5-FU (150 mg/kg b. wt.) or saline (control) on day 8 to induce mucositis. Results We found that vit. E supplementation ameliorated 5-FU-induced lipid peroxidation, myeloperoxidase activity, activation of nuclear factor kappaB, expression of cyclooxygenase-2, inducible nitric oxide synthase and mucin depletion. Vit. E administration also attenuated 5-FU-induced histological anomalies such as neutrophil infiltration, loss of cellular integrity, villus and crypt deformities. ConclusionsFindings of the study suggest that vit. E inhibits 5-FU-induced mucositis via modulation of oxidative stress, activation of redox sensitive transcription factor and its downstream targets. PMID- 27682717 TI - Bis-Michael Acceptors as Novel Probes to Study the Keap1/Nrf2/ARE Pathway. AB - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator that promotes the transcription of cytoprotective genes in response to oxidative/electrophilic stress. Various Michael-type compounds were designed and synthesized, and their potency to activate the Keap1/Nrf2/ARE pathway was evaluated. Compounds bearing two Michael-type acceptors proved to be the most active. Tether length and rigidity between the acceptors was crucial. This study will help to understand how this feature disrupts the interaction between Keap1 and Nrf2. PMID- 27682718 TI - Accuracy of staging of oral squamous cell carcinoma of the tongue: should incisional biopsy be done before or after magnetic resonance imaging? AB - Accurate staging of oral squamous cell carcinoma (oral SCC) is essential. Some clinicians delay diagnostic biopsy until after magnetic resonance imaging (MRI). We retrospectively studied the clinical records and histopathological databases of 58 patients with SCC of the tongue; 39 had biopsy before MRI and 19 afterwards. In the group who had the biopsy first, eight were up-staged, nine were down-staged, and in 22 the T stage was accurate. In those who had MRI first, the corresponding figures were two, six, and 11, respectively. The time between initial biopsy and excision was significantly longer in the MRI group (43 days), than in the biopsy group (16 days) (p<0.001). Differences in staging between the two groups were not significant. Whether the biopsy was taken before or after MRI does not seem to affect the accuracy of clinical staging, and to delay biopsy until after staging may be unnecessary. PMID- 27682719 TI - Tattoos: could they be used to advantage as a medical alert in oral and maxillofacial surgery? AB - Many publications have addressed the medical complications of tattoos, but to our knowledge there are no reports of their use to alert people in our field of potentially dangerous conditions. We present a new way to inform oral and maxillofacial colleagues about patients with a history of malignant hyperthermia (or any other life-threatening medical problem) and discuss the potential advantages and disadvantages of medical alert tattoos. PMID- 27682721 TI - A Win-Win Tool for Improving Local Public Health. PMID- 27682720 TI - Violence Is a Public Health Issue. PMID- 27682722 TI - A Timely Reflection on the Public Health Workforce. PMID- 27682723 TI - Succession Planning and Management Practice in Washington State Local Public Health Agencies. AB - CONTEXT: Turnover of top local public health officials is expected to be great, with 23% being 60 years of age or older, and another 42% being 50 to 59 years of age. Yet, we know little about the use of succession planning in public health agencies. OBJECTIVE: Describe succession planning practices in local public health agencies. DESIGN: We conducted a Web-based, cross-sectional survey of succession planning practices and followed the career paths of public health officials for 40 months. SETTING AND PARTICIPANTS: The top local public health officials from Washington State's 35 local governmental public health agencies. MAIN OUTCOME MEASURES: Twenty-five succession planning best practices. RESULTS: All 35 agencies responded, resulting in a 100% response rate. Our study found evidence of succession planning practices in Washington State local public health agencies: 85% of agencies selected high-performing high potential employees for development, 76% sent them to formal technical and management/leadership training, 70% used cross-functional team projects, and 67% used stretch assignments to develop their employees. Impetuses to implement succession planning were discovering that large percentages of employees were able to retire soon and that national accreditation requires workforce development plans. Barriers to implementing succession planning included other competing demands for time, belief that the agency's workforce was too small for a formal program, and concerns that there would be union barriers. In 2012, 50% of the officials surveyed said that it would be at least possible that they would leave their current jobs within 5 years. Forty months later, 12 (34%) had left their positions. CONCLUSIONS: We were encouraged by the level of succession planning in Washington State and recommend creating a greater sense of urgency by focusing on agency retirement profiles and emphasizing the need for workforce development plans for accreditation. Developing the public health leaders of tomorrow is too important to be left to chance. PMID- 27682724 TI - State Public Health Enabling Authorities: Results of a Fundamental Activities Assessment Examining Core and Essential Services. AB - CONTEXT: Public health enabling authorities establish the legal foundation for financing, organizing, and delivering public health services. State laws vary in terms of the content, depth, and breadth of these fundamental public health activities. Given this variance, the Institute of Medicine has identified state public health laws as an area that requires further examination. To respond to this call for further examination, the Centers for Disease Control and Prevention's Public Health Law Program conducted a fundamental activities legal assessment on state public health laws. OBJECTIVE: The goal of the legal assessment was to examine state laws referencing frameworks representing public health department fundamental activities (ie, core and essential services) in an effort to identify, catalog, and describe enabling authorities of state governmental public health systems. DESIGN: In 2013, Public Health Law Program staff compiled a list of state statutes and regulations referencing different commonly-recognized public health frameworks of fundamental activities. The legal assessment included state fundamental activities laws available on WestlawNext as of July 2013. The results related to the 10 essential public health services and the 3 core public health functions were confirmed and updated in June 2016. RESULTS: Eighteen states reference commonly-recognized frameworks of fundamental activities in their laws. Thirteen states have listed the 10 essential public health services in their laws. Eight of these states have also referenced the 3 core public health functions in their laws. Five states reference only the core public health functions. CONCLUSIONS: Several states reference fundamental activities in their state laws, particularly through use of the essential services framework. Further work is needed to capture the public health laws and practices of states that may be performing fundamental activities but without reference to a common framework. PMID- 27682725 TI - Wage Inequity: Within-Market Comparative Analysis of Salary for Public Health Nurses and Hospital Nurses. AB - The labor market perspective focuses on supply and demand for registered nurses (RNs) as employees. This perspective contrasts with beliefs in the public health sector that RNs working in local health departments (LHD) as public health nurses (PHNs) accept lower wages because of factors other than market demand. This study sought to describe the extent to which hourly wages of RNs working in LHDs are competitive with hospital RN wages within the same county market. A repeated measures survey design was used in collecting 2010 and 2014 data. The unit of analysis was the county, as an RN labor market for LHDs and hospitals. Survey questions captured factors common in human resources benefits and wage packages, such as differential pay, hourly rate pay based on years of experience, components of benefit packages (eg, sick and vacation leave), and reimbursement for education. Within each county, the LHD and all hospitals constituted a "market," yielding a potential 12 markets in our study sample. Human resources representatives from each of the 12 LHDs and from all hospitals within those 12 counties were invited to participate. We conducted comparisons with survey data using t test of mean differences on mean RN wages across years of experience. On average, LHDs paid significantly less than hospitals in their markets, at all levels of RN experience, and this gap increased with RN experience in the sample markets. Salary compression was evident in 2010 and worsened for PHNs in 2014, when compared with hospital RNs. In 2014, 100% of the sample LHDs offered reimbursements for continuing education for PHNs compared with 89% of hospitals providing this benefit. This study contributes to our understanding of the human resources challenges faced by LHDs and provides evidence elucidating resources issues that need to be addressed in order to improve recruitment and retention of PHNs. PMID- 27682726 TI - Assessment of National CLAS Standards in Rural and Urban Local Health Departments in Kentucky. AB - CONTEXT: Findings from the Centers for Disease Control and Prevention suggest that addressing persistent health disparities based on race and ethnicity must become a national priority. The field of cultural and linguistic competency has gained national attention by improving access to and quality of health care, patient-provider communication, health outcomes, and health equity for minority groups and other vulnerable or special needs populations. OBJECTIVES: (1) To measure how local health departments (LHDs) in Kentucky comply with the National Standards for Culturally and Linguistically Appropriate Services (CLAS); and (2) to provide policy recommendation based on the findings. This study is the first to assess a statewide public health system under the lens of CLAS. DESIGN: Analysis of cross-sectional survey. SETTING: Electronic surveys administered to LHD administrators in Kentucky. PARTICIPANTS: Public health directors, nurse leaders, and program managers. MAIN OUTCOME MEASURE: Levels of compliance with various CLAS standards were examined for rural and urban counties using a novel scoring method. RESULTS: A total of 159 LHD administrators received the survey. Response rate was 67% (106 participants). Rural and urban LHDs achieved moderate compliance on domains of plans and policies, quality monitoring and improvement for needs assessment, management information systems for clients, and staff training and development. Both geographic groups exhibited lesser compliance on domains of organizational governance, culturally inclusive health care environment for educational materials, and diversity of personnel recruitment. CONCLUSION: County and district LHDs in Kentucky have implemented activities and policies that comply with CLAS standards at levels that vary by domain. Areas requiring particular attention include organizational governance, culturally inclusive health care environment for educational materials, and diversity of personnel. Improvements in these areas may help LHDs better meet the needs of vulnerable populations, racial and ethnic minorities, and special needs groups. CLAS practices may allow organizations to adhere to national public health accreditation standards. PMID- 27682728 TI - A Century in the Life of the Control of Communicable Diseases Manual: 1917 to 2017. AB - The Control of Communicable Diseases Manual, a premier publication of the American Public Health Association, celebrates its centennial in 2017. The Control of Communicable Diseases Manual has evolved in format and content through 20 separate editions. This article is a follow-up to an earlier article, titled "Evolution of the Control of Communicable Disease Manual: 1917 to 2000," that appeared in the Journal of Public Health Management & Practice in 2001. Our update focuses on the period since the 17th edition, which is characterized by dramatic changes. The 20th edition (2014) added a few arboviral diseases (Banna, Cache Valley, Eyach, Heartland, severe fever with thrombocytopenia syndrome virus, Iquitos, and Me Tri), but mostly contracted, leaving 65 arboviral entries. Other categories of pathogens also declined in the most recent editions, indicating an apparent trend to make the manual less encyclopedic. We attempt to explain these and other changes and ask the reader to comment whether they are aware of other related facts or history based on personal experience. PMID- 27682729 TI - Building the Business Case for Public Health Information Systems. PMID- 27682730 TI - ASTHO President's Challenge-Health Is Community. PMID- 27682727 TI - Development and Usefulness of a District Health Systems Tool for Performance Improvement in Essential Public Health Functions in Botswana and Mozambique. AB - INTRODUCTION: This study describes the development of a self-audit tool for public health and the associated methodology for implementing a district health system self-audit tool that can provide quantitative data on how district governments perceive their performance of the essential public health functions. METHODS: Development began with a consensus-building process to engage Ministry of Health and provincial health officers in Mozambique and Botswana. We then worked with lists of relevant public health functions as determined by these stakeholders to adapt a self-audit tool describing essential public health functions to each country's health system. We then piloted the tool across districts in both countries and conducted interviews with district health personnel to determine health workers' perception of the usefulness of the approach. RESULTS: Country stakeholders were able to develop consensus around 11 essential public health functions that were relevant in each country. Pilots of the self-audit tool enabled the tool to be effectively shortened. Pilots also disclosed a tendency to upcode during self-audits that was checked by group deliberation. Convening sessions at the district enabled better attendance and representative deliberation. Instant feedback from the audit was a feature that 100% of pilot respondents found most useful. CONCLUSION: The development of metrics that provide feedback on public health performance can be used as an aid in the self-assessment of health system performance at the district level. Measurements of practice can open the door to future applications for practice improvement and research into the determinants and consequences of better public health practice. The current tool can be assessed for its usefulness to district health managers in improving their public health practice. The tool can also be used by the Ministry of Health or external donors in the African region for monitoring the district-level performance of the essential public health functions. PMID- 27682731 TI - A Look at Local Public Health Governance: Findings From the 2015 Local Board of Health National Profile. PMID- 27682732 TI - A Tribute to Dr Harrison Spencer. PMID- 27682733 TI - Response to Scanlan Concerning: Measurement of Health Disparities, Health Inequities, and Social Determinants of Health to Support the Advancement of Health Equity. PMID- 27682734 TI - Editor's Note. PMID- 27682735 TI - Implementing Health Impact Assessment Programs in State Health Agencies: Lessons Learned From Pilot Programs, 2009-2011. AB - CONTEXT: Health Impact Assessment (HIA) has emerged as a promising tool to integrate health considerations into decision making. The growth and success of HIA practice in the United States will be dependent on building the capacity of practitioners. OBJECTIVE: This article seeks to identify the role of state health agencies (SHAs) in building capacity for conducting HIAs and the key components of initiatives that produced effective HIAs and HIA programs. The authors proposed to answer 3 research questions: (1) What can be the role of the SHA in HIA? (2) What are the characteristics of successful state HIA programs? and (3) What are some effective strategies for building capacity for HIA in SHAs and local health departments? DESIGN: The authors reviewed program reports from the ASTHO's pilot state health agencies (California, Minnesota, Oregon, and Wisconsin) that, between 2009 and 2011, created HIA programs to provide HIA training, conduct HIAs, and build practitioner networks. MAIN OUTCOME MEASURES: Program reports were examined for shared themes on the role of SHAs in a statewide HIA initiative, the characteristics of successful programs, and effective strategies for building capacity. RESULTS: Despite differences among the programs, many shared themes existed. These include stressing the importance of a basic, sustained infrastructure for HIA practice; leveraging existing programs and networks; and working in partnership with diverse stakeholders. CONCLUSIONS: SHAs can build capacity for HIA, and SHAs can both lead and support the completion of individual HIAs. States and territories interested in starting comprehensive statewide HIA initiatives could consider implementing the strategies identified by the pilot programs. PMID- 27682738 TI - The future of multiple sclerosis treatments. AB - INTRODUCTION: There are not many conditions in which the last few decades have brought such a major change in the landscape of treatments as is the case of multiple sclerosis (MS). A number of disease modifying treatments (DMTs) are presently available for the treatment of the inflammatory phase of this disabling disease; however, the need for treating neurodegeneration and halting the progression of disability is still unmet. Areas covered: In this paper we review the available information on existing and emerging DMTs and we discuss their place within the context of different treatment strategies in MS, Expert commentary: The future of MS treatments should include the development of new treatment strategies tackling disease progression, together with a better understanding of the side-effects and the best sequential strategy of implementation of available and emerging drugs. PMID- 27682736 TI - Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone targeted contrast agent. AB - Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone targeted MR imaging contrast agent, Gd2-diethylenetriaminepentaacetate bis(alendronate) (Gd2-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pKa, complex constant, and T1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd2-DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd2-DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r1) of 7.613mM-1s-1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd2-DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd2 DTPA-BA. The signal intensity of Gd2-DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd2-DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd2-DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. PMID- 27682737 TI - Evaluation of antioxidant and stabilizing lipid peroxidation nature of Solanum xanthocarpum leaves in experimentally diethylnitrosamine induced hepatocellular carcinogenesis. AB - Solanum xanthocarpum Schrad. & Wendl, is a traditional edible leaves as a form of decoction, extracts used as a herbal medicine, and consumed for health promoting profiles. The present investigation was carried out to evaluate antioxidant status and lipid peroxidation level of anticancer activity of Solanum xanthocarpum (SXC) on Diethylnitrosamine (DEN) induced hepato carcinogenesis in male Wistar albino rats. Hepatic cancer was developed on the liver of Wistar rats treated by DEN or vehicle three times a week for 16 weeks. Tumour incidence, tumour volume, tumour burden, lipid peroxidation, antioxidant, liver marker enzymes and histopathological changes were assessed in DEN alone and in DEN+SXC leaves extract treated rats. Hundred percent tumour incidences with an imbalance in carcinogen metabolizing enzymes and cellular redox status were observed in rats treated with DEN alone. Oral administration of SXC aqueous leaves extract treatment at a dose of 150mg/kg b.w. to DEN treated rats were prevented tumour incidence and restored the elevated activities of liver marker enzymes and antioxidant status to near normal with decreased lipid peroxide levels. The biochemical consistent with histopathological observations suggesting marked hepatoprotective effect of the leaves extract in a dose dependent manner. These results clearly suggest that SXC aqueous leaves extract treatment prevents liver damage, lipid peroxidation, protects the antioxidant defense system and anti carcinogenic potential in DEN induced hepatic carcinogenesis. PMID- 27682739 TI - A systematic review of patient-practitioner communication interventions involving treatment decisions. AB - OBJECTIVES: To examine the: 1) methodological quality of interventions examining strategies to improve patient-practitioner communication involving treatment decisions; 2) effectiveness of strategies to improve patient-practitioner communication involving treatment decisions; and 3) types of treatment decisions (emergency/non-emergency) in the included studies. METHODS: Medline, PsychINFO, CINAHL, and Embase were searched to identify intervention studies. To be included, studies were required to examine patient-practitioner communication related to decision making about treatment. Study methodological quality was assessed using Cochrane's Effective Practice and Organisation of Care risk of bias criteria. Study design, sample characteristics, intervention details, and outcomes were extracted. RESULTS: Eleven studies met the inclusion criteria. No studies were rated low risk on all nine risk of bias criteria. Two of the three interventions aimed at changing patient behaviour, two of the five practitioner directed, and one of the three patient-practitioner directed interventions demonstrated an effect on decision-making outcomes. No studies examined emergency treatment decisions. CONCLUSIONS: Existing studies have a high risk of bias and are poorly reported. There is some evidence to suggest patient-directed interventions may be effective in improving decision-making outcomes. PRACTICE IMPLICATIONS: It is imperative that an evidence-base is developed to inform clinical practice. PMID- 27682740 TI - Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood brain barrier and targeted fluorescence imaging of glioma and tumor vasculature. AB - Delivery of imaging agents to brain glioma is challenging because the blood-brain barrier (BBB) functions as a physiological checkpoint guarding the central nervous system from circulating large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots (QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides (NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs. Our data showed that the NGR-PEG-QDs were nanoscale with less than 100 nm and were stable in various pH (4.0~8.0). These nanomaterials with non-toxic concentrations could cross the BBB and target CD13-overexpressing glioma and tumor vasculature in vitro and in vivo, contributing to fluorescence imaging of this brain malignancy. These achievements allowed groundbreaking technological advances in targeted fluorescence imaging for the diagnosis and surgical removal of glioma, facilitating potential transformation toward clinical nanomedicine. PMID- 27682741 TI - Pulmonary adenocarcinomas presenting as ground-glass opacities on multidetector CT: three-dimensional computer-assisted analysis of growth pattern and doubling time. AB - PURPOSE: We aimed to evaluate the growth pattern and doubling time (DT) of pulmonary adenocarcinomas exhibiting ground-glass opacities (GGOs) on multidetector computed tomography (CT). METHODS: The growth pattern and DT of 22 pulmonary adenocarcinomas exhibiting GGOs were retrospectively analyzed using three-dimensional semiautomatic software. Analysis of each lesion was based on calculations of volume and mass changes and their respective DTs throughout CT follow-up. Three-dimensional segmentation was performed by a single radiologist on each CT scan. The same observer and another radiologist independently repeated the segmentation at the baseline and the last CT scan to determine the variability of the measurements. The relationships among DTs, histopathology, and initial CT features of the lesions were also analyzed. RESULTS: Pulmonary adenocarcinomas presenting as GGOs exhibited different growth patterns: some lesions grew rapidly and some grew slowly, whereas others alternated between periods of growth, stability, or shrinkage. A significant increase in volume and mass that exceeded the coefficient of repeatability of interobserver variability was observed in 72.7% and 84.2% of GGOs, respectively. The volume-DTs and mass DTs were heterogeneous throughout the follow-up CT scan (range, -4293 to 21928 and -3113 to 17020 days, respectively), and their intra- and interobserver variabilities were moderately high. The volume-DTs and mass-DTs were not correlated with the initial CT features of GGOs; however, they were significantly shorter in invasive adenocarcinomas (P = 0.002 and P = 0.001, respectively). CONCLUSION: Pulmonary adenocarcinomas exhibiting GGOs show heterogeneous growth patterns with a trend toward a progressive increase in size. DTs may be useful for predicting tumor aggressiveness. PMID- 27682743 TI - Can Anal Sphincter Defects Be Identified by Palpation? AB - OBJECTIVES: The aim of this study was to correlate clinical findings of anal sphincter defects and function with a sonographic diagnosis of significant sphincter defects. METHODS: This is an observational cross-sectional study on women seen 6 to 10 weeks after primary repair of obstetric anal sphincter injuries (OASIs). All patients underwent a standardized interview including the St Mark incontinence score, a digital rectal examination, and 3-/4-dimensional transperineal ultrasound imaging. RESULTS: Two hundred forty-five patients were seen after primary repair of OASIs. Mean age was 29 (17-43) years. They were assessed at a median of 58 (15-278) days postpartum. One hundred fifty-seven (64%) delivered normal vaginally, 72 (29%) delivered by vacuum, and 16 (7%) delivered by forceps. A comparison of external anal sphincter (EAS) and internal anal sphincter ultrasound volume data and palpation was possible in 220 and 212 cases, respectively. Sphincter defects at rest and on contraction were both detected clinically in 17 patients. Significant abnormalities of the EAS were diagnosed on tomographic ultrasound imaging in 99 cases (45%), and significant abnormalities of the internal anal sphincter were diagnosed in 113 cases (53%). Agreement between digital and sonographic findings of sphincter defect was poor (k = 0.03-0.08). Women with significant EAS defects on ultrasound were found to have a lower resistance to digital insertion (P = 0.018) and maximum anal squeeze (P = 0.009) on a 6-point scale. The difference was however small. CONCLUSIONS: Digital rectal examination does not seem to be sufficiently sensitive to diagnose residual sphincter defects after primary repair of OASIs. Imaging is required for the evaluation of sphincter anatomy after repair. PMID- 27682742 TI - Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage. AB - OBJECTIVES: To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059). METHOD: Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated. RESULTS: The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score <= 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively. CONCLUSIONS: In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti TNF) therapy. MBDA scores were elevated in all patients with structural damage progression. PMID- 27682744 TI - Insurance Type and Major Complications After Hysterectomy. AB - OBJECTIVES: The aim of this study was to investigate the relationship between primary insurance type and major complications after hysterectomy. METHODS: A retrospective analysis was performed on women with Medicaid, Medicare, and private insurance who underwent hysterectomy from January 1, 2012, to July 1, 2014, and were included in the Michigan Surgical Quality Collaborative. Major complications within 30 days of surgery included the following: deep/organ space surgical site infection, deep venous and pulmonary thromboembolism, myocardial infarction or stroke, pneumonia or sepsis, blood transfusion, readmission, and death. Multivariable logistic regression was used to identify factors associated with major complications and characteristics associated with the Medicaid and Medicare groups. RESULTS: A total of 1577 women had Medicaid, 2103 had Medicare, and 11,611 had private insurance. The Medicaid and Medicare groups had a similar rate of major complications, nearly double that of the private insurance group (6.85% vs 7.85% vs 3.79%; P < .001). Compared with private insurance, women with Medicaid and Medicare had increased odds of major complications (Medicaid: odds ratio [OR], 1.60; 95% confidence interval [CI], 1.26-2.04; P < .001; Medicare: OR, 1.34; 95% CI, 1.04-1.73; P = .03). Women with Medicaid were more likely to be nonwhite, have a higher body mass index (BMI), report tobacco use in the last year and undergo an abdominal hysterectomy. Those with Medicare were more likely to be white, to have gynecologic cancer, and to be functionally dependent. Both groups had increased odds of American Society of Anesthesiology class 3 or higher and decreased odds of undergoing hysterectomy at large hospitals (>=500 beds). CONCLUSIONS: Women with Medicaid and Medicare insurance have increased odds of major complications after hysterectomy. Abdominal hysterectomy, BMI, and smoking are potentially modifiable risk factors for women with Medicaid. PMID- 27682745 TI - Effect of a New Risk Calculator on Patient Satisfaction With the Decision for Concomitant Midurethral Sling During Prolapse Surgery: A Randomized Controlled Trial. AB - OBJECTIVE: To determine whether use of a new personalized risk calculator increases patient satisfaction with the decision whether or not to have a prophylactic midurethral sling (MUS) during pelvic organ prolapse (POP) surgery. METHODS: We performed a randomized controlled trial involving English-speaking women without symptoms of stress urinary incontinence (SUI) with >= stage 2 POP who planned to undergo POP surgery with 1 of 4 fellowship-trained urogynecologists at a single academic center. Women with a history of prior POP or incontinence surgery, or who were pregnant, or unable to complete study forms were excluded. Participants were randomly assigned to standard preoperative counseling or preoperative counseling with the use of a validated, online risk calculator for de novo SUI after POP surgery. The primary outcome was patient satisfaction with the decision for prophylactic MUS placement during POP surgery at 3 months postoperative assessed using the Satisfaction with Decision Scale for Pelvic Floor Disorders. RESULTS: Sixty-three women were approached for participation. Forty-two agreed to participate, 41 underwent randomization, and 33 had POP surgery and completed 3-month follow-up. Of these 33, 17 were randomized to the risk calculator and 16 to standard counseling. The mean age was 61.2 +/- 9.1 years, and 41% (14/33) had a prophylactic MUS. At 3 months postoperative, there was no difference in Satisfaction with Decision Scale for Pelvic Floor Disorders scores between groups (4.67 +/- 0.46 [intervention] vs 4.78 +/- 0.34 [control]; P = 0.61). CONCLUSIONS: Use of the de novo SUI risk calculator did not increase patient satisfaction with the decision regarding MUS placement during POP surgery. PMID- 27682746 TI - Perioperative Complications and Cost of Vaginal, Open Abdominal, and Robotic Surgery for Apical Vaginal Vault Prolapse. AB - OBJECTIVES: To determine the rate of perioperative complications and cost associated with Mayo-McCall culdoplasty (MMC), open abdominal sacrocolpopexy (ASC), and robotic sacrocolpopexy (RSC) for posthysterectomy vaginal vault prolapse. METHODS: We retrospectively searched for the records of patients undergoing posthysterectomy apical vaginal prolapse surgery (MMC, ASC, or RSC) between January 1, 2000, and June 30, 2012, at our institution. For all patients identified, perioperative complications, length of hospital stay, and inpatient costs to patients were abstracted from the medical records and compared by procedure. Inverse-probability-of-procedure weighting using propensity scores was used to obtain less-biased comparisons of outcomes between procedures. RESULTS: A total of 512 patients met the inclusion criteria (174 MMC, 237 ASC, and 101 RSC). Using inverse-probability weighting, the MMC group had a significantly lower intraoperative complication rate (3.3% vs 11.6% for ASC, 3.4% vs 24.1% for RSC), median operative time (94 vs 217 min for ASC, 100 vs 228 min for RSC), and median cost (US $8,776 vs $12,695 for ASC, US $8,773 vs $13,107 for RSC) than the ASC and RSC groups (all P < 0.01). In addition, the MMC group had significantly fewer postoperative grade 3+ complications than the RSC group (1.1% vs 9.4%, P < 0.01). CONCLUSIONS: In the treatment of posthysterectomy vaginal vault prolapse, MMC is associated with decreased non-urinary tract infection, less perioperative morbidity, and lower cost to patients compared with sacrocolpopexy. PMID- 27682747 TI - Anatomical Relationships of Burch Colposuspension Sutures. AB - OBJECTIVES: The prevalent use of minimally invasive midurethral slings for the treatment of stress urinary incontinence in the last several decades has resulted in fewer Burch procedures being performed and diminished surgical experience in performing the Burch colposuspension. However, recent antimesh media has resulted in more patients requesting nonmesh anti-incontinence procedures and a subsequent need for surgeons to refamiliarize themselves with the Burch procedure and its relevant anatomy. The objective of this study was to evaluate the relationships of Burch sutures to surrounding neurovascular anatomic structures in the human cadaver. METHODS: The retropubic space of 11 unembalmed female cadavers was dissected, and a Burch procedure performed. The distance from the Burch sutures' location through both Cooper's ligament and the vagina to the obturator neurovascular bundle and external iliac vessels was measured. RESULTS: The mean distance from the most lateral stitch in Cooper's ligament to the obturator bundle was 25.9 +/- 7.6 mm and to the external iliac vessels was 28.9 +/- 9.3 mm, and in some instances, these structures were less than 1.5 cm away. CONCLUSIONS: The obturator bundle and external iliac lie, on average, within 3 cm of sutures placed during a Burch colposuspension. Knowledge of these anatomical relationships is valuable when dissecting the space of Retzius and placing sutures for a Burch to avoid injury. PMID- 27682748 TI - Voiding Function After Midurethral Slings With and Without Local Anesthetic: Randomized Controlled Trial. AB - OBJECTIVES: This study aimed to compare the effect of periurethral infiltration of bupivacaine versus normal saline on postoperative voiding function and pain in patients undergoing retropubic midurethral sling METHODS: A randomized double blind placebo-controlled study was performed at the University of Massachusetts from March 2012 to June 2015. Ninety patients were randomized to receive 0.5% bupivacaine with epinephrine or normal saline with epinephrine solution for periurethral hydrodissection. Postoperative pain was assessed at 2 to 3 and 6 to 7 hours using a visual analog scale. Voiding function was determined by the proportion of subjects passing or failing a voiding trial. Descriptive statistics and percentages were used to compare the rate of voiding dysfunction. A logistic regression analysis was performed adjusting for possible covariates. RESULTS: Ninety subjects enrolled and 45 were randomized to each group. Thirty-nine subjects received the normal saline and 41 received bupivacaine. The remaining 10 withdrew before the procedure. Pain scores at 2 to 3 hours did not differ between the groups (P = 0.837), but at 6 to 7 hours, patients who received bupivacaine had less pain (P = 0.028). There was no difference in voiding dysfunction between the study and placebo groups (17.9% and 24.4%, respectively; P = 0.481). Because of the unavailability of indigo carmine midway through the study, 36 of 80 subjects received preoperative phenazopyridine for the assessment of ureteral patency. Three (8%) of these subjects failed their voiding trial compared with 19 (30%) of the patients who did not receive phenazopyridine (P = 0.010). CONCLUSIONS: The use of bupivacaine did not affect postoperative voiding function but had lower pain scores at 6 to 7 hours postoperatively. Preoperative phenazopyridine may reduce postoperative urinary retention. PMID- 27682750 TI - ? AB - Nursing Practice has always sought to address issues relevant to practising nurses. Clinical grading is a subject which has attracted a lot of coverage in the nursing press; not least because of the dissatisfaction of many clinical nurses with their grading and subsequent delays in appeals. PMID- 27682751 TI - Health care research: Measuring health status. AB - The NHS White Paper working document entitled 'Contracts for services and the role of district health authorities' ( 1 ) emphasised the need for providers to guarantee appropriate care with optimum clinical outcome. One of the issues that will be increasingly topical is: what methods exist for evaluating the effectiveness, or outcome, of treatment or care? PMID- 27682749 TI - Association of Mechanism of Injury With Risk for Venous Thromboembolism After Trauma. AB - Importance: To date, no study has assessed whether the risk of venous thromboembolism (VTE) varies with blunt or penetrating trauma. Objective: To test whether the mechanism of injury alters risk of VTE after trauma. Design, Setting, and Participants: A retrospective database review was conducted of adults admitted to the intensive care unit of an American College of Surgeons-verified level I trauma center between August 1, 2011, and January 1, 2015, with blunt or penetrating injuries. Univariate and multivariable analyses identified independent predictors of VTE. Main Outcomes and Measures: Differences in risk factors for VTE with blunt vs penetrating trauma. Results: In 813 patients with blunt trauma (mean [SD] age, 47 [19] years) and 324 patients with penetrating trauma (mean [SD] age, 35 [15] years), the rate of VTE was 9.1% overall (104 of 1137) and similar between groups (blunt trauma, 9% [n = 73] vs penetrating trauma, 9.6% [n = 31]; P = .76). In the blunt trauma group, more patients with VTE than without VTE had abnormal coagulation results (49.3% vs 35.7%; P = .02), femoral catheters (9.6% vs 3.9%; P = .03), repair and/or ligation of vascular injury (15.1% vs 5.4%; P = .001), complex leg fractures (34.2% vs 18.5%; P = .001), Glasgow Coma Scale score less than 8 (31.5% vs 10.7%; P < .001), 4 or more transfusions (51.4% vs 17.6%; P < .001), operation time longer than 2 hours (35.6% vs 16.4%; P < .001), and pelvic fractures (43.8% vs 21.4%; P < .001); patients with VTE also had higher mean (SD) Greenfield Risk Assessment Profile scores (13 [6] vs 8 [4]; P <= .001). However, with multivariable analysis, only receiving 4 or more transfusions (odds ratio [OR], 3.47; 95% CI, 2.04-5.91), Glasgow Coma Scale score less than 8 (OR, 2.75; 95% CI, 1.53-4.94), and pelvic fracture (OR, 2.09; 95% CI, 1.23-3.55) predicted VTE, with an area under the receiver operator curve of 0.730. In the penetrating trauma group, more patients with VTE than without VTE had abnormal coagulation results (64.5% vs 44.4%; P = .03), femoral catheters (16.1% vs 5.5%; P = .02), repair and/or ligation of vascular injury (54.8% vs 25.3%; P < .001), 4 or more transfusions (74.2% vs 39.6%; P < .001), operation time longer than 2 hours (74.2% vs 50.5%; P = .01), Abbreviated Injury Score for the abdomen greater than 2 (64.5% vs 42.3%; P = .02), and were aged 40 to 59 years (41.9% vs 23.2%; P = .02); patients with VTE also had higher mean (SD) Greenfield Risk Assessment Profile scores (12 [4] vs 7 [4]; P < .001). However, with multivariable analysis, only repair and/or ligation of vascular injury (OR, 3.32; 95% CI, 1.37-8.03), Abbreviated Injury Score for the abdomen greater than 2 (OR, 2.77; 95% CI, 1.19-6.45), and age 40 to 59 years (OR, 2.69; 95% CI, 1.19-6.08) predicted VTE, with an area under the receiver operator curve of 0.760. Conclusions and Relevance: Although rates of VTE are the same in patients who experienced blunt and penetrating trauma, the independent risk factors for VTE are different based on mechanism of injury. This finding should be a consideration when contemplating prophylactic treatment protocols. PMID- 27682753 TI - A Charter for 'patients'. AB - The more often trains are delayed the less likely anybody is to rely on them. And although British Rail distributes a proliferation of timetables, regular commuters regard the published times with a healthy dose of scepticism. People have begun to expect a lower standard of service as the norm. PMID- 27682752 TI - Calcium alginate: A dressing trial. AB - Venous leg ulcers and pressure sores are common problems that afflict elderly, chronically ill, debilitated or paralysed patients. They cause considerable discomfort and distress to the patient and take up large amounts of nursing time, frequently resulting in long hospital stays. They are liable to become infected, necrotic and produce considerable amounts of exudate. PMID- 27682754 TI - 'Heavy tax demands' looming for HAs. AB - Health authorities could face 'substantial and unexpected demands' for back tax and national insurance contributions in the near future, tax experts have claimed. PMID- 27682755 TI - Proposed charter can offer improved care. AB - Nurses and midwives have strongly urged the Government to use the proposed Patient's Charter as a tool for 'active and responsive' primary health care. PMID- 27682756 TI - Nurses' pay. AB - As staff-side representatives prepare to submit their evidence to the Review Body on nurses' pay next week, independent experts have predicted that public service pay will rise by 7 per cent in 1992-93 at a cost to the Government of L2 billion more than estimated. PMID- 27682757 TI - ? AB - Life cycle: Amateur cyclists rode from Bath and Bristol to London last week in the Audi 100 charity bike ride to raise money for Action Research. PMID- 27682758 TI - Row over infection control guidelines. AB - NUPE is demanding to know why hospital Trusts are not obliged to obey new Health Department infection control guidelines on HIV and Hepatitis B. PMID- 27682759 TI - NHS down 80,000 nurses, says Cook. AB - Under the Conservative Government the National Health Service has lost more than 80,000 nurses and one in five beds, Labour Health Spokesman Robin Cook said last week. PMID- 27682761 TI - BPA set to investigate lack of paediatric ICUs. AB - The lack of paediatric intensive-care beds often results in children being cared for in adult intensive-care units (ICU) or on general children's wards, according to the British Paediatric Association (BPA). PMID- 27682762 TI - Toe-nail avulsion. AB - This trial compares the efficiency of Comfeel Ulcer Dressing (Coloplast Ltd), a hydrocolloid dressing, with a chlorhexidine acetate impregnated dressing on iatrogenic wounds produced by toe-nail avulsion followed by treatment with phenolisation of the germinal matrix and nail bed. PMID- 27682763 TI - No care provisions for elderly people. AB - Many health authorities have little or no provision for elderly people who need continuing care, says a new report from the charity Age Concern. PMID- 27682765 TI - Holistic nursing care praised. AB - Aromatherapy and alternative medicine can enhance what nurses do every day, Helen Passant, a clinical nurse specialist told a conference last week. PMID- 27682764 TI - Patients' views. AB - Users of health and local authority services need to be consulted more often, according to a new report from the National Council for Voluntary Organisations (NCVO). PMID- 27682766 TI - ? AB - Sisters Myfanwy Khan, left, Elizabeth Harris and Yvonne Sterenborg handed over their great-grandfather's medals to a representative of the Army Museum at RCN head office last week. The former Army surgeon won at least one of the medals for his work in the Crimea and named his daughter after Florence Nightingale. PMID- 27682767 TI - Health information act. AB - Nurses have welcomed legislation allowing patients greater freedom to see their medical records. PMID- 27682768 TI - Nursing practice. AB - The crucial Step in a nurse's development is the one from being a competent to a proficient practitioner, according to leading American author and researcher, Patricia Benner. PMID- 27682769 TI - Reasons for leaving among psychiatric nurses: A two-year prospective study. AB - Recruiting and retaining nursing staff has been increasingly identified by nurse managers and the media as a problem of 'crisis' proportions, but until recently there has been very little systematic research into what factors influence the nurse to leave. The present study addressed this issue and asks: 'Why do nurses leave?' and 'What happens to them once they do leave?' This study was a follow-up to an earlier one by Bamber ( 1 ) and aimed to generate new information which would either support or reject the findings of the earlier study. PMID- 27682770 TI - Nurse is suing for burns compensation. AB - A nurse who claims she suffered injury as a result of chemical exposure at Basildon and Orsett Hospitals in Essex is suing for compensation. PMID- 27682771 TI - Eye tests. AB - Pensioners and those on low incomes who find it difficult to get out to the optitians will soon be able to get their optitian to visit them. PMID- 27682772 TI - Declaration attacks HIV discrimination. AB - Nurses and doctors who refuse to care for people with HIV and AIDS should be struck off by their professional bodies, Jonathan Grimshaw told a press conference last week. PMID- 27682773 TI - Managing the patient with fractured femur. PMID- 27682774 TI - 'Secret plans' to cut London HAs alleged. AB - The four Thames Regional Health Authorities are drawing up secret plans to cut the number of health authorities in the capital from 28 to 11 over the next two and a half years, the pressure group London Health Emergency has claimed. PMID- 27682776 TI - Evaluating a change to primary nursing: Some methodological issues. AB - Research studies which have been designed to evaluate the introduction of primary nursing as a method of organising the delivery of care frequently use an 'experimental' research design. Experimental research studies use the terms 'independent variable' and 'dependent variable'. There is assumed to be a relationship between the independent variable and the dependent variable so that manipulation of the independent variable causes a change in the dependent variable. PMID- 27682777 TI - Music proves therapeutic to pain levels. AB - Music may reduce the experience of pain during minor surgical procedures. PMID- 27682778 TI - Meningitis outcome, symptom-duration link. AB - The duration of symptoms in children with bacterial meningitis might be an indicator of prognosis. PMID- 27682779 TI - Tattoo parlours in need of tighter control. AB - Registration and tighter controls on tattoo parlours by environmental health officers have been called for. PMID- 27682780 TI - Teeth under attack from savoury snacks. AB - Crisps and savoury snacks are not the best nibble to bridge the gap, at least as far as your teeth are concerned. PMID- 27682781 TI - Fat embolism risk from closed manipulation. AB - Massive fat embolism may be a rare but life-threatening complication of closed manipulation of bones, say researchers. PMID- 27682782 TI - Barley extract cream for pressure sores. AB - Vast numbers of elderly patients suffering from pressure sores may soon find relief from a cream based on barley extract. PMID- 27682783 TI - Postmenopausal risk of myocardial infarction. AB - Postmenopausal women taking tamoxifen for at least five years are less likely to the from myocardial infarction (MI), an Edinburgh research project suggests. PMID- 27682784 TI - Portable records are a help to the homeless. AB - Portable medical records can be used successfully by mentally ill homeless people, a major study has revealed. PMID- 27682785 TI - Relieving emetic side-effect of chemotherapy. AB - Two of the most distressing side-effects of chemotherapy, nausea and vomiting, can severely impair the quality of life of cancer sufferers and may result in non compliance with prescribed treatment. PMID- 27682786 TI - World news. AB - What's happening in nursing across the globe. PMID- 27682788 TI - Friend or foe? AB - He is popularly described as a maverick, a Conservative traditionalist, and a thorn in the side of the Government, especially after he cast his vote against the NHS reforms. He is man of strong views, passionate beliefs and single-minded determination. PMID- 27682787 TI - Informal carers of the dementing elderly: A study of relationships. AB - The role of informal carers in the UK has been a cause of considerable concern recently and has been highlighted by the Government's legislation of 1988 ( 1 ). PMID- 27682789 TI - Moral dilemmas in nursing research. AB - The aim of this paper is to address the complex issue of moral dilemmas which can exist in the realm of research using human subjects. Two such dangers of exploitation are breaching the confidentiality of the patient and not securing an informed consent ( 1 , 2 ). PMID- 27682790 TI - Orem and the nursing process: New directions for the 1990s. AB - Orem considers that the activities or operations of the nursing process involve both technical and professional aspects of nursing. The term technologic professional operations is now used as a general description of all the activities a nurse must present when performing nursing duties. These technologic professional operations form the basis of the nursing process and include the following steps: diagnostic, prescriptive, treatment/regulatory and case management. PMID- 27682792 TI - Losing all credibility. AB - After reading Derek Hand's article 'Equal only on paper' (Nursing Standard August 11), I still cannot believe that the NHS is any less committed to equal opportunities than any other employer. PMID- 27682791 TI - Ward placements should come free. AB - Everyone knows that nurse education is expensive. But has cost been ignored, or is it too difficult to quantify? Two years ago, nursing colleges tried to generate income by selling services to the independent sector. PMID- 27682793 TI - No support for prodigal nurses? AB - After a 15-year absence from hospital nursing, my mother, an RGN, returned to the profession at the age of 52. PMID- 27682794 TI - Correction. AB - Pauline Ford, Royal College of Nursing Advisor in Care of the Elderly, was incorrectly credited with writing the document 'The Role of the Nurse in Rehabilitation of Elderly People' (Nursing Standard August 28 - page 9 ). PMID- 27682795 TI - Information exchange. AB - We are a community hospital, caring mainly for the elderly, offering interim and rehabilitation care following an acute admission to a district general hospital. PMID- 27682796 TI - ? PMID- 27682797 TI - Points of View. AB - Are the NHS reforms really about providing a quality health care service? PMID- 27682798 TI - Accident and emergency nursing: A new approach Accident and emergency nursing: A new approach G Jones Faber 154pp L5.99 0-571-14319-9 [Formula: see text]. AB - Gary Jones's A&E book is one with a difference. He I begins with the development of the service and its emergence in nursing as a specialty, with a look forward to developing a philosophy for care. PMID- 27682799 TI - Primary Nursing in Perspective S Ersser Primary Nursing in Perspective and E Tutton Scutari Press 286pp L17.95 1-871364-36-3 [Formula: see text]. AB - Primary Nursing in Perspective is an extremely detailed analysis of not just the practice of primary nursing but the history and philosophy behind the concept. It's attractive and well-presented with clearly defined sections, each written by nurses, teachers and researchers involved in primary nursing. PMID- 27682800 TI - Critical Care Nursing of the Surgical Patient Critical Care Nursing of the Surgical Patient M Shekleton K Litwack W B Saunders 658pp L27.00 0-7126-3090-1 [Formula: see text]. AB - Critical Care Nursing of the Surgical Patient promises little and lives up to its promise. It's difficult for me to understand why, apparently, we need more books of this sort. I am always impressed by the amount of effort that goes into the writing, editing, referencing, indexing and production. I can forgive the ; failure to make any attempt to adapt the book for the British reader. More difficult to forget, as I read, is the gradually failing vision of the editors. PMID- 27682802 TI - Listings. AB - Nursing Standard regrets that owing to unprecedented demand we are no longer able to take listings over the telephone. We would like to remind our readers that the listings section is for use by charitable organisations, unions, professional organisations and health authorities to publicise forthcoming events. Your listings should contain all relevant details and be posted or faxed to Jo Barr, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow, Middlesex HA1 2AX (Fax 081-423 3867). PMID- 27682801 TI - Eye structure: A functional view. AB - In schools, universities and many colleges of nursing, the anatomy and physiology of the eye is taught from a very structured 'three coat' perspective. The existing knowledge of nurses undertaking post- basic courses is often based on this structural approach. PMID- 27682805 TI - Polysorbate-80-coated, polymeric curcumin nanoparticles for in vivo anti depressant activity across BBB and envisaged biomolecular mechanism of action through a proposed pharmacophore model. AB - Depression is a modern world epidemic. Its main causative factor is oxidative stress, as reported in study subjects. Natural products are yet to show significant therapeutic effects in comparison with synthetic drugs. Current study deals with the preparation of brain-targeted polysorbate-80-coated curcumin PLGA nanoparticles (PS-80-CUR-NP), and their characterisation via Spectral and optical methods. PS-80-CUR-NP were evaluated against the oxidative stress-mediated depressant (OSMD) activity via Force despair, Tail suspension tests and stress biomarker assay (SOD and catalase activity). A significant reduction in immobility (p < 0.01) in force despair and tail suspension test and a significant increase (p < 0.001 and p < 0.01) in SOD and catalase activity was found and compared with stress control, which confirmed the OSMD activity of PS-80-CUR-NP at 5 mg equivalent dose. Further, AUC(0.5-15 h) curve of brain homogenates estimated the curcumin concentration of 1.73 ng/g C max at T max 3 h via HPLC technique. PMID- 27682803 TI - Phylogenetic Identification, Phenotypic Variations, and Symbiotic Characteristics of the Peculiar Rhizobium, Strain CzR2, Isolated from Crotalaria zanzibarica in Taiwan. AB - Crotalaria zanzibarica is an exotic and widely distributed leguminous plant in Taiwan. The relationship between C. zanzibarica and its rhizobial symbionts has been suggested to contribute to its successful invasion. A rhizobial strain (designed as CzR2) isolated from the root nodules of C. zanzibarica and cultivated in standard YEM medium displayed pleomorphism, with cells ranging between 2 and 10 MUm in length and some branching. In the present study, we identified this rhizobial strain, investigated the causes of pleomorphism, and examined the nodules formed. The results of a multilocus sequence analysis of the atpD, dnaK, glnII, gyrB, recA, and rpoB genes revealed that CzR2 belongs to Bradyrhizobium arachidis, a peanut symbiont recently isolated from China. Cells of the strain were uniformly rod-shaped in basal HM medium, but displayed pleomorphism in the presence of yeast extract, mannitol, or fructose. These results indicate that the morphology of CzR2 in its free-living state is affected by nutrient conditions. Several highly pleomorphic bacteroids enclosed in symbiosomes were frequently detected in FM and TEM observations of sections of the indeterminate nodules induced by CzR2; however, no infection thread was identified. Flow cytometric analyses showed that CzR2 cells in YEM medium and in the nodules of C. zanzibarica had two or more than two peaks in relative DNA contents, respectively, suggesting that the elongated cells of CzR2 in its free living state occur due to a cell cycle-delayed process, while those in its symbiotic state are from genomic endo-reduplication. PMID- 27682806 TI - Does tranexamic acid improve outcomes in traumatic brain injury? PMID- 27682804 TI - In Situ Cultivation Allows for Recovery of Bacterial Types Competitive in Their Natural Environment. AB - Standard cultivation fails to grow most microorganisms, whereas in situ cultivation allows for the isolation of comparatively diverse and novel microorganisms. Information on similarities and differences in the physiological properties of isolates obtained from in situ cultivation and standard cultivation is limited. Therefore, we used the arctic sediment samples and compared two culture collections obtained using standard and novel cultivation techniques. Even though there was no temperature selection at the isolation step, isolates from each method showed different reactions to temperature. The results of the present study suggest that isolates from in situ cultivation are more competitive in their natural environment. PMID- 27682807 TI - Striatal mitochondria response to 3-nitropropionic acid and fish oil treatment. AB - BACKGROUND: Mitochondrial dysfunction is involved in neurodegenerative diseases, such as Huntington's disease (HD). 3-Nitropropionic acid (3-NP) is a mitochondrial toxin that specifically inhibits complex II of the electron transport chain (ETC) and is used to generate an experimental model of HD. OBJECTIVE: To study the effect of fish liver oil (FO) over the mitochondrial dysfunction induced via partial ETC inhibition by 3-NP. METHODS: This study was performed in rats and consisted of two phases: (i) administration of increasing doses of 3-NP and (ii) administration of FO for 14 days before to 3-NP. The rats' exploratory activity; complex I, II, III, and IV activities; and rearing behavior were observed. Additionally, the number of TUNEL-positive cells and various mitochondrial parameters, including oxygen consumption, transmembrane potential, adenosine triphosphate synthesis, and ETC activity, were measured. RESULTS: We observed that FO exerted a protective effect against the 3-NP-induced toxicity, although complex II inhibition still occurred. Instead, this effect was related to strengthened mitochondrial complex III and IV activities. DISCUSSION: Our results show that FO exerts a beneficial prophylactic effect against mitochondrial damage. Elucidating the mechanisms linking the effects of FO with its prevention of neurodegeneration could be the key to developing recommendations for FO consumption in neurological pathologies. PMID- 27682808 TI - Incidence and predictors of cardiovascular events in a cohort of patients with rheumatoid arthritis. AB - INTRODUCTION: An excess in cardiovascular (CV) morbidity and mortality has been recognized in Rheumatoid Arthritis (RA) patients when compared to the general population. Given the paucity of prospective data, our aim was to estimate the incidence of CV events and the contribution of traditional CVD risk factors and RA-related parameters to future events. METHODS: Incident fatal and non-fatal CV events (hospitalizations due to unstable angina, myocardial infarction, coronary artery revascularization procedures, stroke, or CV death) were assessed in a prospective cohort of RA women followed since 2007 and without CV events at cohort entry. The presence of traditional CV risk factors, disease characteristics, medication, carotid ultrasound, and biomarkers of inflammation and endothelial activation were evaluated at baseline. Univariate Cox proportional hazard models were used to identify risk factors for CV events. RESULTS: Among 106 women followed over 565 patient-years we identified 4 CV events (1 fatal stroke, 2 myocardial infarction and 1 unstable angina), which contributed to an incidence rate of 7 per 1000 person-years (95%CI 2.0- 13.9). Patients who developed CV events were older, but the distribution of other traditional CV risk factors was otherwise similar in both groups. Also, corticosteroid dosage and proportion of patients with carotid atherosclerotic plaques was higher in those with CV events. Erythrocyte sedimentation rate (ESR) (HR 1.036; 95%CI 1.005-1.067) and soluble intercellular adhesion molecule-1 (sICAM-1) serum levels (HR 1.002; 95%CI 1.000-1.003) significantly contributed to CV events. These results remained significant after adjusting for patients' age. CONCLUSION: We found an incidence of cardiovascular events in women with RA of 7 per 1000 patent-years. This value is similar to that found in other Portuguese cohort of RA patients1 and much higher than the incidence reported for the general Portuguese population. Markers of inflammation and endothelial activation contributed significantly to CV events, but the limited number of events prevents further analysis. PMID- 27682809 TI - Intrathecal baclofen withdrawal: A rare cause of reversible cardiomyopathy. AB - Baclofen is commonly used to treat spasticity of central etiology. Unfortunately, a potentially lethal withdrawal syndrome can complicate its use. This is especially true when the drug is administered intrathecally. There are very few cases of baclofen withdrawal leading to reversible cardiomyopathy described in the literature. The authors present a patient with a history of chronic intrathecal baclofen use who, in the setting of acute baclofen withdrawal, develops laboratory, electrocardiogram, and echocardiogram abnormalities consistent with cardiomyopathy. Upon reinstitution of intrathecal baclofen, the cardiomyopathy and associated abnormalities quickly resolve. Although rare, it is crucial to be aware of this reversible cardiomyopathy to ensure its prompt diagnosis and treatment. PMID- 27682811 TI - Steady-state equation of water vapor sorption for CaCl2-based chemical sorbents and its application. AB - Green CaCl2-based chemical sorbent has been widely used in sorption refrigeration, air purification and air desiccation. Methods to improve the sorption rate have been extensively investigated, but the corresponding theoretical formulations have not been reported. In this paper, a sorption system of solid-liquid coexistence is established based on the hypothesis of steady state sorption. The combination of theoretical analysis and experimental results indicates that the system can be described by steady-state sorption process. The steady-state sorption equation, MU = (eta - gammaT) , was obtained in consideration of humidity, temperature and the surface area. Based on engineering applications and this equation, two methods including an increase of specific surface area and adjustment of the critical relative humidity (gamma) for chemical sorbents, have been proposed to increase the sorption rate. The results indicate that the CaCl2/CNTs composite with a large specific surface area can be obtained by coating CaCl2 powder on the surface of carbon nanotubes (CNTs). The composite reached sorption equilibrium within only 4 h, and the sorption capacity was improved by 75% compared with pure CaCl2 powder. Furthermore, the addition of NaCl powder to saturated CaCl2 solution could significantly lower the solution's gamma. The sorption rate was improved by 30% under the same environment. PMID- 27682810 TI - Discovery of Novel Viruses in Mosquitoes from the Zambezi Valley of Mozambique. AB - Mosquitoes carry a wide variety of viruses that can cause vector-borne infectious diseases and affect both human and veterinary public health. Although Mozambique can be considered a hot spot for emerging infectious diseases due to factors such as a rich vector population and a close vector/human/wildlife interface, the viral flora in mosquitoes have not previously been investigated. In this study, viral metagenomics was employed to analyze the viral communities in Culex and Mansonia mosquitoes in the Zambezia province of Mozambique. Among the 1.7 and 2.6 million sequences produced from the Culex and Mansonia samples, respectively, 3269 and 983 reads were classified as viral sequences. Viruses belonging to the Flaviviridae, Rhabdoviridae and Iflaviridae families were detected, and different unclassified single- and double-stranded RNA viruses were also identified. A near complete genome of a flavivirus, tentatively named Cuacua virus, was obtained from the Mansonia mosquitoes. Phylogenetic analysis of this flavivirus, using the NS5 amino acid sequence, showed that it grouped with 'insect-specific' viruses and was most closely related to Nakiwogo virus previously identified in Uganda. Both mosquito genera had viral sequences related to Rhabdoviruses, and these were most closely related to Culex tritaeniorhynchus rhabdovirus (CTRV). The results from this study suggest that several viruses specific for insects belonging to, for example, the Flaviviridae and Rhabdoviridae families, as well as a number of unclassified RNA viruses, are present in mosquitoes in Mozambique. PMID- 27682812 TI - Intermolecular Amination of Unactivated C(sp3 )-H Bonds with Cyclic Alkylamines: Formation of C(sp3 )-N Bonds through Copper/Oxygen-Mediated C(sp3 )-H/N-H Activation. AB - The first example of intermolecular amination of unactivated C(sp3 )-H bonds by cyclic alkylamines mediated by Cu(OAc)2 /O2 is reported. This method avoids the use of benzoyloxyamines as the aminating reagent, which are normally prepared from alkylamines in extra steps. A variety of unnatural beta2, 2 -amino acid analogues are synthesized by this simple and efficient procedure. This approach offers a solution to the previous unmet challenge of C(sp3 )-H/N-H activation for the formation of C(sp3 )-N bonds. PMID- 27682813 TI - Diaphragmatic Dysfunction Is Characterized by Increased Duration of Mechanical Ventilation in Subjects With Prolonged Weaning. AB - BACKGROUND: Diaphragmatic dysfunction is often underdiagnosed and is among the risk factors for failed weaning. The purpose of this study was to determine the prevalence of diaphragmatic dysfunction diagnosed by B-mode ultrasonography and to determine whether prolonged weaning subjects with diaphragmatic dysfunction have increased duration of mechanical ventilation compared with those without diaphragmatic dysfunction. METHODS: This was a prospective observational study in mechanically ventilated subjects who failed >=3 spontaneous breathing trials or required >7 d of weaning after the first spontaneous breathing trial. Diaphragm thickness was measured in the zone of apposition using a 6-13-MHz ultrasound transducer during a spontaneous breathing trial. The diaphragmatic thickening fraction was calculated as a percentage from the formula: (Thickness at peak inspiration - thickness at end expiration)/thickness at end expiration. Intra observer and inter-observer reliability were also evaluated. RESULTS: Forty-one subjects (24 males; 62.2 +/- 15.9 y old) were included in the study. Of these, the prevalence of ultrasonographic diaphragmatic dysfunction (defined as diaphragmatic thickening fraction of <20% with inspiration) was 34.1% (n = 14). Subjects with diaphragmatic dysfunction had longer ventilation time after inclusion (293.4 +/- 194.8 vs 145.1 +/- 101.3 h, P = .02) and ICU stay (29.2 +/- 11.4 vs 22.4 +/- 7.7 d, P = .03) than subjects without diaphragmatic dysfunction. CONCLUSIONS: Diaphragmatic dysfunction as assessed by B-mode ultrasonography is common in subjects with prolonged weaning. Subjects with such diaphragmatic dysfunction show longer mechanical ventilation durations and ICU stays. PMID- 27682814 TI - Should the 6-Minute Walk Test Be Compared When Conducted by 2 Different Assessors in Subjects With COPD? AB - BACKGROUND: The 6-min walk test (6MWT) is an important tool in the assessment of functional capacity and prognosis in patients with COPD. However, especially in long-term follow-up in clinical settings, this test may be executed by a different assessor, and it is not well known whether 6MWT has an acceptable inter rater reliability. The aim of this study is to analyze the intra- and inter-rater reliability of the performance in 6MWT, its cardiorespiratory changes, and effort perception in subjects with COPD. METHODS: Thirty-two subjects with a diagnosis of COPD participated in the study, but 3 subjects did not appear on the second day of evaluation and therefore were included only in the intra-rater analysis; the first and second tests were executed by the same assessor with a 30-min interval between them, and the last was executed by a different assessor a week later. The intra-rater reliability was verified comparing the first and second 6MWT performance, and the inter-rater reliability was verified comparing the third test with the best performance of the first and second tests. RESULTS: The intraclass correlation coefficient values were >0.75 (P < .001) for the walked distance on the 6MWT; however, the limits of agreement, SE of measurement, and minimal detectable difference were higher than the minimum clinically important differences already mentioned in the literature (~25, 26, and 54 m), and the coefficient of variation was small in both intra- and inter-rater comparisons. CONCLUSIONS: The 6MWT showed excellent reliability for distance and perceived exertion and moderate to excellent for HR and SD as assessed by intra- and inter rater analysis. Thus, based on the main study outcomes, we concluded that the 6MWT can be compared when conducted by 2 different evaluators. PMID- 27682815 TI - Electrical Impedance Tomography During Mechanical Ventilation. AB - Electrical impedance tomography (EIT) is a noninvasive, non-radiologic imaging modality that may be useful for the quantification of lung disorders and titration of mechanical ventilation. The principle of operation is based on changes in electrical conductivity that occur as a function of changes in lung volume during ventilation. EIT offers potentially important benefits over standard imaging modalities because the system is portable and non-radiologic and can be applied to patients for long periods of time. Rather than providing a technical dissection of the methods utilized to gather, compile, reconstruct, and display EIT images, the present article seeks to provide an overview of the clinical application of this technology as it relates to monitoring mechanical ventilation and providing decision support at the bedside. EIT has been shown to be useful in the detection of pneumothoraces, quantification of pulmonary edema and comparison of distribution of ventilation between different modes of ventilation and may offer superior individual titration of PEEP and other ventilator parameters compared with existing approaches. Although application of EIT is still primarily done within a research context, it may prove to be a useful bedside tool in the future. However, head-to-head comparisons with existing methods of mechanical ventilation titration in humans need to be conducted before its application in general ICUs can be recommended. PMID- 27682816 TI - Is Extracorporeal Membrane Oxygenation Saving Lives, or Are We Just Using It in Healthier Patients? PMID- 27682818 TI - Editor's Commentary. PMID- 27682817 TI - Heated Humidified High-Flow Nasal Cannula: Impact on Neonatal Outcomes. PMID- 27682819 TI - The effect of perceived psychological stress on the immunogenicity of the quadrivalent human papillomavirus vaccine in males. AB - BACKGROUND: The human papillomavirus (HPV) vaccine is recommended for male and female recipients aged 9-26 years, and is effective in preventing HPV infection and cancer precursors. However, there is variability in immunogenicity among recipients as measured by anti-HPV geometric mean titers. In this study, we explored the effect of stress level on the immunogenicity of the HPV vaccine among college age males. METHODS: 220 males aged 18-25 y were randomly assigned to 6-month (0, 2, and 6) and 12-month (0, 2, and 12) dosing schedules. Antibody titers were measured before the first dose and 2-6 weeks following the final dose. We recorded participants' age and stress level, based on a 4-item Perceived Stress Scale (PSS-4) questionnaire. RESULTS: The average age of participants was 21.3 y old. Inspection of titers by quartile on the stress scale generally showed highest titers with highest stress. Spearman correlation coefficients revealed significant correlation between stress and titers for HPV-6, 16, and 18 but not for HPV-16 in the group of 6-month dosing schedule; no associations were found for the 12-month dosing schedule. For most strains, linear regression revealed significant (P > 0.05) associations on antibody titer for categorical age and dosing schedule but not stress. CONCLUSION: The evidence is mixed for an association between stress and HPV vaccine response for the 6-month dosing schedule, but no association was found for stress for the 12-month dosing schedule. Further investigations with larger and more diverse population groups are needed to explore the association between stress level and vaccine immunogenicity. PMID- 27682821 TI - Crystal structures of mono- and bi-specific diabodies and reduction of their structural flexibility by introduction of disulfide bridges at the Fv interface. AB - Building a sophisticated protein nano-assembly requires a method for linking protein components in a predictable and stable structure. Diabodies are engineered antibody fragments that are composed of two Fv domains connected by short peptide linkers. They are attractive candidates for mediators in assembling protein nano-structures because they can simultaneously bind to two different proteins and are rigid enough to be crystallized. However, comparison of previous crystal structures demonstrates that there is substantial structural diversity in the Fv interface region of diabodies and, therefore, reliable prediction of its structure is not trivial. Here, we present the crystal structures of ten mono- and bi-specific diabodies. We found that changing an arginine residue in the Fv interface to threonine greatly reduced the structural diversity of diabodies. We also found that one of the bispecific diabodies underwent an unexpected process of chain swapping yielding a non-functional monospecific diabody. In order to further reduce structural flexibility and prevent chain shuffling, we introduced disulfide bridges in the Fv interface regions. The disulfide-bridged diabodies have rigid and predictable structures and may have applications in crystallizing proteins, analyzing cryo-electron microscopic images and building protein nano assemblies. PMID- 27682822 TI - New Insights on the Regulation of Ca2+ -Activated Chloride Channel TMEM16A. AB - TMEM16A, also known as anoctamin 1, is a recently identified Ca2+ -activated chloride channel and the first member of a 10-member TMEM16 family. TMEM16A dysfunction is implicated in many diseases such as cancer, hypertension, and cystic fibrosis. TMEM16A channels are well known to be dually regulated by voltage and Ca2+ . In addition, recent studies have revealed that TMEM16A channels are regulated by many molecules such as calmodulin, protons, cholesterol, and phosphoinositides, and a diverse range of stimuli such as thermal and mechanical stimuli. A better understanding of the regulatory mechanisms of TMEM16A is important to understand its physiological and pathological role. Recently, the crystal structure of a TMEM16 family member from the fungus Nectria haematococcaten (nhTMEM16) is discovered, and provides valuable information for studying the structure and function of TMEM16A. In this review, we discuss the structure and function of TMEM16A channels based on the crystal structure of nhTMEM16A and focus on the regulatory mechanisms of TMEM16A channels. J. Cell. Physiol. 232: 707-716, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27682824 TI - Source of CpG Depletion in the HIV-1 Genome. AB - The dinucleotide CpG is highly underrepresented in the genome of human immunodeficiency virus type 1 (HIV-1). To identify the source of CpG depletion in the HIV-1 genome, we investigated two biological mechanisms: (1) CpG methylation induced transcriptional silencing and (2) CpG recognition by Toll-like receptors (TLRs). We hypothesized that HIV-1 has been under selective evolutionary pressure by these mechanisms leading to the reduction of CpG in its genome. A CpG depleted genome would enable HIV-1 to avoid methylation-induced transcriptional silencing and/or to avoid recognition by TLRs that identify foreign CpG sequences. We investigated these two hypotheses by determining the sequence context dependency of CpG depletion and comparing it with that of CpG methylation and TLR recognition. We found that in both human and HIV-1 genomes the CpG motifs flanked by T/A were depleted most and those flanked by C/G were depleted least. Similarly, our analyses of human methylome data revealed that the CpG motifs flanked by T/A were methylated most and those flanked by C/G were methylated least. Given that a similar CpG depletion pattern was observed for the human genome within which CpGs are not likely to be recognized by TLRs, we argue that the main source of CpG depletion in HIV-1 is likely host-induced methylation. Analyses of CpG motifs in over 100 viruses revealed that this unique CpG representation pattern is specific to the human and simian immunodeficiency viruses. PMID- 27682823 TI - Excitation of lateral habenula neurons as a neural mechanism underlying ethanol induced conditioned taste aversion. AB - KEY POINTS: The lateral habenula (LHb) has been implicated in regulation of drug seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. ABSTRACT: Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg-1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced the magnitude of lever press-evoked inhibition. Finally, firing rates were significantly higher during consumption of the devalued saccharin solution after CTA induction. Next, we studied sham- and LHb-lesioned rats in our operant CTA paradigm and found that LHb lesion significantly attenuated CTA effects in the operant task. Our data demonstrate the importance of LHb excitation in regulating expression of ethanol-induced aversion and suggest a mechanism for its role in modulating escalation of voluntary ethanol intake. PMID- 27682825 TI - Rapid and efficient enantioseparation of (S)-amlodipine by surface-imprinted core shell polymer microspheres. AB - We present a protocol for the preparation of surface-imprinted polymer microspheres by core-shell precipitation polymerization for the enantioseparation of (S)-amlodipine. In this work, submicron mesoporous silica microspheres were prepared with gemini cationic surfactant as soft template. Molecularly imprinted polymers were coated on the silica supports with a low level of crosslinking, and the thickness of the thin-walled imprinted shell was about 45 nm. The material showed fast binding kinetics for (S)-amlodipine (within only 20 min for complete equilibrium), and the saturation adsorption capacity reached 309.2 mg/g, indicating the good accessibility of binding sites and improved mass transfer for target molecule. The imprinted microspheres exhibited an appreciable enantiomeric excess of (S)-amlodipine of 11.3% when used as a glass chromatography column for the enantioseparation of (S)-amlodipine from amlodipine besylate without extra chiral additives. The surface-imprinted materials display potentially amplification for industrial enantioseparation of (S)-amlodipine. PMID- 27682826 TI - Predictors of Acute Vertebrobasilar Vasospasm following Tumor Resection in the Foramen Magnum Region. AB - OBJECTIVE: Cerebral vasospasm can occur after skull base tumor removal. Few studies concentrated on the posterior circulation vasospasm after tumor resection in the posterior fossa. We aimed to identify the risk factors associated with postoperative vertebrobasilar vasospasm after tumor resection in the foramen magnum. METHODS: We retrospectively reviewed the data of 62 patients with tumors in the foramen magnum at our institution from January 2010 to January 2015. The demographic data, tumor features, surgical characteristics were collected. Vertebrobasilar vasospasm was evaluated by bedside transcranial Doppler before surgery and on postoperative day 1, 3, 7. Univariate and multivariate analyses were performed to determine the predictors of postoperative vasospasm in the posterior circulation. RESULTS: Vertebrobasilar vasospasm was detected in 28 (53.8%) of the 62 patients at a mean time of 3.5 days after surgery. There were 5 (8%) patients with severe vasospasm according to the grading criteria. Age, tumor type, tumor size, vertebral artery encasement, and surgical time were significantly related to vasospasm in the univariate analysis. Further multivariate analysis demonstrated that only age and vertebral artery encasement were independent risk factors predicting the occurrence of postoperative vertebrobasilar vasospasm. CONCLUSIONS: The incidence of acute vertebrobasilar vasospasm is not uncommon after foramen magnum tumor resection. Age and vertebral artery encasement are significantly correlated with postoperative vasospasm. Close monitoring of vasospasm should be given to patients with younger age and the presence of vertebral artery encasement on the preoperative imaging to facilitate early diagnosis and intervention. PMID- 27682827 TI - Validity of aqueous flare measurement in predicting proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. AB - PURPOSE: To investigate aqueous flare as a preoperative predictor for later proliferative vitreoretinopathy (PVR) development in patients with rhegmatogenous retinal detachment (RD) and to determine the validity of this measurement in patients at low clinical risk for postoperative PVR. METHODS: This study included 100 eyes of 100 patients who underwent surgery for primary RD. Aqueous flare was determined preoperatively with a laser flare-cell meter (Kowa FM-500, Kowa Company Ltd, Tokyo, Japan). Patients were followed for at least 6 months postoperatively. Failures related to PVR were recorded for statistical analysis. RESULTS: Twenty eyes (20%) developed PVR postoperatively. Preoperative flare values in these eyes were significantly higher than in eyes with no redetachment (48.12 +/- 61.24 versus 17.74 +/- 29.63 photon counts per millisecond (pc/ms), p = 0.002). The odds ratio for PVR development with flare values >15 pc/ms was 12.3 (p < 0.0001, 95% confidence interval, 3.54-42.59). Of 54 eyes at low clinical risk for postoperative PVR, five developed PVR postoperatively. Flare values were significantly higher in these eyes (25.30 +/- 7.10 pc/ms) than in eyes with no redetachment (12.44 +/- 10.16 pc/ms, p = 0.008). Using logistic regression, the odds ratio of PVR redetachment risk increased by the factor 1.078 per 1 pc/ms of flare value (95% CI, 1.01-1.15). CONCLUSION: Preoperative aqueous flare is a strong predictive factor for PVR redetachment. The laser flare-cell meter provides a fast and safe tool to accurately identify patients at risk for postoperative PVR, especially when clinical examination did not predict this risk. PMID- 27682828 TI - Countries publishing in JAN. PMID- 27682820 TI - A central role for calcineurin in protein misfolding neurodegenerative diseases. AB - Accumulation of misfolded/unfolded aggregated proteins in the brain is a hallmark of many neurodegenerative diseases affecting humans and animals. Dysregulation of calcium (Ca2+) and disruption of fast axonal transport (FAT) are early pathological events that lead to loss of synaptic integrity and axonal degeneration in early stages of neurodegenerative diseases. Dysregulated Ca2+ in the brain is triggered by accumulation of misfolded/unfolded aggregated proteins in the endoplasmic reticulum (ER), a major Ca2+ storing organelle, ultimately leading to neuronal dysfunction and apoptosis. Calcineurin (CaN), a Ca2+/calmodulin-dependent serine/threonine phosphatase, has been implicated in T cells activation through the induction of nuclear factor of activated T cells (NFAT). In addition to the involvement of several other signaling cascades, CaN has been shown to play a role in early synaptic dysfunction and neuronal death. Therefore, inhibiting hyperactivated CaN in early stages of disease might be a promising therapeutic strategy for treating patients with protein misfolding diseases. In this review, we briefly summarize the structure of CaN, inhibition mechanisms by which immunosuppressants inhibit CaN, role of CaN in maintaining neuronal and synaptic integrity and homeostasis and the role played by CaN in protein unfolding/misfolding neurodegenerative diseases. PMID- 27682830 TI - The role of mutation analysis of the APC gene in the management of FAP patients. A controversial issue. AB - BACKGROUND: A correlation between the location of mutation in the adenomatous polyposis coli (APC) gene and clinical manifestations of familial adenomatous polyposis (FAP) has repeatedly been reported. Some Authors suggest the use of mutational analysis as a guide to select the best surgical option in FAP patients. However, data coming from studies on large series have raised questions on this issue. The aim of this study is to discuss the role of the genetic tests in the management of FAP. METHODS: A literature review was performed considering only peer-reviewed articles published between 1991-2015. All the studies examined the role of genetic as a guide for surgical management of FAP. RESULTS: Of 363 articles identified, 21 were selected for full-text review. We found different positions with regard the use of genetic tests to determine surgical management of FAP. In particular, while consistent correlations between the APC mutation site and FAP phenotype were observed in large series, 8 studies reported a wide variation of genotypephenotype correlation in patients with the same mutation and they recommended that decisions regarding surgical strategy should be based not only on genotype but also on the clinical factors and the will of the patient who must be fully informed. CONCLUSIONS: The decision on the type and the timing of surgery should be based on the assessment of many factors and genotype assessment should be used in combination with clinical data. KEY WORDS: Disease severity, Familial adenomatous polyposis, Genetic tests, Genotype-phenotype correlations, Surgical management. PMID- 27682831 TI - Occupational Justice: Moral Imagination, Critical Reflection, and Political Praxis. PMID- 27682829 TI - Transcriptome Analysis of the Response to NaCl in Suaeda maritima Provides an Insight into Salt Tolerance Mechanisms in Halophytes. AB - Although salt tolerance is a feature representative of halophytes, most studies on this topic in plants have been conducted on glycophytes. Transcriptome profiles are also available for only a limited number of halophytes. Hence, the present study was conducted to understand the molecular basis of salt tolerance through the transcriptome profiling of the halophyte Suaeda maritima, which is an emerging plant model for research on salt tolerance. Illumina sequencing revealed 72,588 clustered transcripts, including 27,434 that were annotated using BLASTX. Salt application resulted in the 2-fold or greater upregulation of 647 genes and downregulation of 735 genes. Of these, 391 proteins were homologous to proteins in the COGs (cluster of orthologous groups) database, and the majorities were grouped into the poorly characterized category. Approximately 50% of the genes assigned to MapMan pathways showed homology to S. maritima. The majority of such genes represented transcription factors. Several genes also contributed to cell wall and carbohydrate metabolism, ion relation, redox responses and G protein, phosphoinositide and hormone signaling. Real-time PCR was used to validate the results of the deep sequencing for the most of the genes. This study demonstrates the expression of protein kinase C, the target of diacylglycerol in phosphoinositide signaling, for the first time in plants. This study further reveals that the biochemical and molecular responses occurring at several levels are associated with salt tolerance in S. maritima. At the structural level, adaptations to high salinity levels include the remodeling of cell walls and the modification of membrane lipids. At the cellular level, the accumulation of glycinebetaine and the sequestration and exclusion of Na+ appear to be important. Moreover, this study also shows that the processes related to salt tolerance might be highly complex, as reflected by the salt-induced enhancement of transcription factor expression, including hormone-responsive factors, and that this process might be initially triggered by G protein and phosphoinositide signaling. PMID- 27682832 TI - Rett syndrome: a wide clinical and autonomic picture. AB - BACKGROUND: Rett Syndrome is a neurodevelopmental disorder almost exclusively affecting females, characterized by a broad clinical spectrum of signs and symptoms and a peculiar course. The disease affects different body systems: nervous, muscolo-skeletal, gastro-enteric. Moreover, part of the symptoms are related to the involvement of the autonomic nervous system. In the Tuscany Rett Center at Versilia Hospital, we collected data from 151 subjects with a clinical diagnosis of classical or variant RTT syndrome. For each subject, we assessed the severity of the condition with clinical-rating scales (ISS, PBZ), we quantified the performance of the autonomic nervous system, and we performed genetic analysis. We used multivariate statistical analysis of the data to evaluate the relation between the different clinical RTT forms, the cardiorespiratory phenotype, the different genetic mutations and the severity of the clinical picture. Individuals were classified according to existing forms: Classical RTT and three atypical RTT: Z-RTT, Hanefeld, Congenital. A correlation between C Terminal deletions and lower severity of the clinical manifestations was evident, in the previous literature, but, considering the analysis of autonomic behaviour, the original classification can be enriched with a more accurate subdivision of Rett subgroups, which may be useful for early diagnosis. RESULTS: Present data emphasize some differences, not entirely described in the literature, among RTT variants. In our cohort the Z-RTT variant cases show clinical features (communication, growth, epilepsy and development), well documented by specific ISS items, less severe, if compared to classical RTT and show autonomic disorders, previously not reported in the literature. In this form epilepsy is rarely present. In contrast, Hanefeld variant shows the constant presence of epilepsy which has an earlier onset In Hanefeld variant the frequency of apneas was rare and, among the cardiorespiratory phenotypes, the feeble type is lacking. CONCLUSION: A quantitative analysis of the different autonomic components reveals differences across typical and atypical forms of RTT that leads to a more accurate classification of the groups. In our cohort of RTT individuals, the inclusion of autonomic parameter in the classification leads to an improved diagnosis at earlier stages of development. PMID- 27682833 TI - Extreme weather events in developing countries and related injuries and mental health disorders - a systematic review. AB - BACKGROUND: Due to climate change, extreme weather events have an incremental impact on human health. Injuries and mental health disorders are a particular burden of disease, which is broadly investigated in high income countries. Most distressed populations are, however, those in developing countries. Therefore, this study investigates mental and physical health impacts arising from extreme weather events in these populations. METHOD: Post-traumatic Stress Disorder (PTSD), injury [primary outcomes], anxiety and depressive disorders [secondary outcomes], caused by weather extremes were systematically analyzed in people of developing countries. A systematic review of observational studies was conducted searching six databases, complemented by hand search, and utilizing two search engines. Review processing was done independently by two reviewers. Prevalence rates were analyzed in a pre/post design; an additional semi-structured search was conducted, to provide reference data for studies not incorporating reference values. RESULTS: All 17 identified studies (70,842 individuals) indicate a disease increase, compared to the reference data. Increase ranges from 0.7-52.6 % for PTSD, and from 0.3-37.3 % for injury. No studies on droughts and heatwaves were identified. All studies were conducted in South America and Asia. CONCLUSION: There is an increased burden of psychological diseases and injury. This finding needs to be incorporated into activities of prevention, preparedness and general health care of those developing countries increasingly experiencing extreme weather events. There is also a gap in research in Africa (in quantity and quality) of studies in this field and a predominant heterogeneity of health assessment tools. PROSPERO registration no.: CRD42014009109. PMID- 27682834 TI - Hemiatrophy of brain: antenatal ultrasonography and MRI/postnatal MRI diagnosis with the introduction of "shifted falx sign". AB - Dyke-Davidoff-Masson syndrome (DDMS) is an uncommon congenital/pediatric disorder diagnosed only with the help of imaging. Clinical features associated with it are hemiparesis, seizures, facial asymmetry, and mental retardation. We here present a case of DDMS diagnosed antenatally at 29 weeks gestational age during routine antenatal ultrasound examination. The patient was further evaluated and followed using both ultrasound and magnetic resonance imaging during antenatal and postnatal periods. The infant had unilateral hemiatrophy with the absence of anterior and middle cerebral arteries. We hereby also want to coin the term "shifted falx sign" as a diagnostic indicator for DDMS for the first time. To our knowledge, this is the earliest antenatally sonologically diagnosed case of the said pathology. PMID- 27682835 TI - Recurrent uterine artery pseudoaneurysm. PMID- 27682836 TI - Large optical nonlinearity of ITO nanorods for sub-picosecond all-optical modulation of the full-visible spectrum. AB - Nonlinear optical responses of materials play a vital role for the development of active nanophotonic and plasmonic devices. Optical nonlinearity induced by intense optical excitation of mobile electrons in metallic nanostructures can provide large-amplitude, dynamic tuning of their electromagnetic response, which is potentially useful for all-optical processing of information and dynamic beam control. Here we report on the sub-picosecond optical nonlinearity of indium tin oxide nanorod arrays (ITO-NRAs) following intraband, on-plasmon-resonance optical pumping, which enables modulation of the full-visible spectrum with large absolute change of transmission, favourable spectral tunability and beam-steering capability. Furthermore, we observe a transient response in the microsecond regime associated with slow lattice cooling, which arises from the large aspect ratio and low thermal conductivity of ITO-NRAs. Our results demonstrate that all optical control of light can be achieved by using heavily doped wide-bandgap semiconductors in their transparent regime with speed faster than that of noble metals. PMID- 27682837 TI - Technical note: how to determine the FDG activity for tumour PET imaging that satisfies European guidelines. AB - BACKGROUND: For tumour imaging with PET, the literature proposes to administer a patient-specific FDG activity that depends quadratically on a patient's body weight. However, a practical approach on how to implement such a protocol in clinical practice is currently lacking. We aimed to provide a practical method to determine a FDG activity formula for whole-body PET examinations that satisfies both the EANM guidelines and this quadratic relation. RESULTS: We have developed a methodology that results in a formula describing the patient-specific FDG activity to administer. A PET study using the NEMA NU-2001 image quality phantom forms the basis of our method. This phantom needs to be filled with 2.0 and 20.0 kBq FDG/mL in the background and spheres, respectively. After a PET acquisition of 10 min, a reconstruction has to be performed that results in sphere recovery coefficients (RCs) that are within the specifications as defined by the EANM Research Ltd (EARL). By performing reconstructions based on shorter scan durations, the minimal scan time per bed position (T min) needs to be extracted using an image coefficient of variation (COV) of 15 %. At T min, the RCs should be within EARL specifications as well. Finally, the FDG activity (in MBq) to administer can be described by [Formula: see text] with c a constant that is typically 0.0533 (MBq/kg(2)), w the patient's body weight (in kg), and t the scan time per bed position that is chosen in a clinical setting (in seconds). We successfully demonstrated this methodology using a state-of-the-art PET/CT scanner. CONCLUSIONS: We provide a practical method that results in a formula describing the FDG activity to administer to individual patients for whole-body PET examinations, taking into account both the EANM guidelines and a quadratic relation between FDG activity and patient's body weight. This formula is generally applicable to any PET system, using a specified image reconstruction and scan time per bed position. PMID- 27682839 TI - Thioflavin T behaves as an efficient fluorescent ligand for label-free ATP aptasensor. AB - Here, we for the first time demonstrated thioflavin T (ThT) as an efficient fluorescent ligand for 27-mer ATP-binding aptamer (ABA27), providing a novel signal readout mode for label-free selective ATP detection. ABA27 can promote the fluorescence emission of ThT with an unprecedentedly high efficiency, attributed to the specific structure of ABA27 rather than the G-tracts. Polyacrylamide gel electrophoresis, fluorescence spectroscopy, and fluorometric titration reveal that ThT interacts with ABA27 with a lower binding affinity (Kd ~89 MUM) than ATP, which allows ATP to easily compete with ThT for the DNA binder. In the presence of ThT, adding ATP induces ABA27 to undergo a structural change, thereby not favoring the binding to ThT, verified by circular dichroism and UV-Vis absorption spectroscopy. As a result, the fluorescence intensity of ThT decreases dramatically, enabling the sensitive detection of ATP with high selectivity over other analogs. Such a sensing strategy may make ThT able to serve as a facile signal reporter for DNA nanomechanical devices fueled with ATP. Graphical Abstract The principle of the displacement of ThT by ATP. PMID- 27682838 TI - A non-enzymatic urine glucose sensor with 2-D photonic crystal hydrogel. AB - A novel polymerized crystalline colloidal array (PCCA) sensing material for the detection of urine glucose was developed by embedding a two-dimensional (2-D) polystyrene crystalline colloidal array (CCA) in 3-acrylamidophenylboronic acid (3-APBA)-functionalized hydrogel. After adjusting the cross-linker concentration, this material showed significant sensitivity for glucose under lab conditions, the particle spacing of the PCCA changed from 917 to 824 nm (93 nm) within 3 min as the glucose concentration increased from 0 to 10 mM, and the structural color of the PCCA changed from red through orange, to green, and finally, to cyan. In further experiments, this material was used to semi-quantitatively detect glucose in 20 human urine (HU) samples. Compared with the traditional dry-chemistry method, which was applied widely in clinical diagnosis, the PCCA method was more accurate and cost-effective. Moreover, this method can efficiently avoid the errors induced by most of the urine-interfering elements like vitamin C and ketone body. With a homemade portable optical detector, this low-cost intelligent sensing material can provide a more convenient and efficient strategy for the urine glucose detection in clinical diagnosis and point-of-care monitoring. PMID- 27682841 TI - An Unbiased Chemical Proteomics Method Identifies FabI as the Primary Target of 6 OH-BDE-47. AB - Determination of the physical interactions of environmental chemicals with cellular proteins is important for characterizing biological and toxic mechanism of action. Yet despite the discovery of numerous bioactive natural brominated compounds, such as hydroxylated polybrominated diphenyl ethers (OH-PBDEs), their corresponding protein targets remain largely unclear. Here, we reported a systematic and unbiased chemical proteomics assay (Target Identification by Ligand Stabilization, TILS) for target identification of bioactive molecules based on monitoring ligand-induced thermal stabilization. We first validated the broad applicability of this approach by identifying both known and unexpected proteins bound by diverse compounds (anticancer drugs, antibiotics). We then applied TILS to identify the bacterial target of 6-OH-BDE-47 as enoyl-acyl carrier protein reductase (FabI), an essential and widely conserved enzyme. Using affinity pull-down and in vitro enzymatic assays, we confirmed the potent antibacterial activity of 6-OH-BDE-47 occurs via direct binding and inhibition of FabI. Conversely, overexpression of FabI rescued the growth inhibition of Escherichia coli by 6-OH-BDE-47, validating it as the primary in vivo target. This study documents a chemical proteomics strategy for identifying the physical and functional targets of small molecules, and its potential high-throughput application to investigate the modes-of-action of environmental compounds. PMID- 27682840 TI - Quantitative imaging of heterogeneous dynamics in drying and aging paints. AB - Drying and aging paint dispersions display a wealth of complex phenomena that make their study fascinating yet challenging. To meet the growing demand for sustainable, high-quality paints, it is essential to unravel the microscopic mechanisms underlying these phenomena. Visualising the governing dynamics is, however, intrinsically difficult because the dynamics are typically heterogeneous and span a wide range of time scales. Moreover, the high turbidity of paints precludes conventional imaging techniques from reaching deep inside the paint. To address these challenges, we apply a scattering technique, Laser Speckle Imaging, as a versatile and quantitative tool to elucidate the internal dynamics, with microscopic resolution and spanning seven decades of time. We present a toolbox of data analysis and image processing methods that allows a tailored investigation of virtually any turbid dispersion, regardless of the geometry and substrate. Using these tools we watch a variety of paints dry and age with unprecedented detail. PMID- 27682842 TI - Computational methods for trajectory inference from single-cell transcriptomics. AB - Recent developments in single-cell transcriptomics have opened new opportunities for studying dynamic processes in immunology in a high throughput and unbiased manner. Starting from a mixture of cells in different stages of a developmental process, unsupervised trajectory inference algorithms aim to automatically reconstruct the underlying developmental path that cells are following. In this review, we break down the strategies used by this novel class of methods, and organize their components into a common framework, highlighting several practical advantages and disadvantages of the individual methods. We also give an overview of new insights these methods have already provided regarding the wiring and gene regulation of cell differentiation. As the trajectory inference field is still in its infancy, we propose several future developments that will ultimately lead to a global and data-driven way of studying immune cell differentiation. PMID- 27682844 TI - Interplay of Cation Ordering and Ferroelectricity in Perovskite Tin Iodides: Designing a Polar Halide Perovskite for Photovoltaic Applications. AB - Owing to its ideal semiconducting band gap and good carrier-transport properties, the fully inorganic perovskite CsSnI3 has been proposed as a visible-light absorber for photovoltaic (PV) applications. However, compared to the organic inorganic lead halide perovskite CH3NH3PbI3, CsSnI3 solar cells display very low energy conversion efficiency. In this work, we propose a potential route to improve the PV properties of CsSnI3. Using first-principles calculations, we examine the crystal structures and electronic properties of CsSnI3, including its structural polymorphs. Next, we purposefully order Cs and Rb cations on the A site to create the double perovskite (CsRb)Sn2I6. We find that a stable ferroelectric polarization arises from the nontrivial coupling between polar displacements and octahedral rotations of the SnI6 network. These ferroelectric double perovskites are predicted to have energy band gaps and carrier effective masses similar to those of CsSnI3. More importantly, unlike nonpolar CsSnI3, the electric polarization present in ferroelectric (CsRb)Sn2I6 can effectively separate the photoexcited carriers, leading to novel ferroelectric PV materials with potentially enhanced energy conversion efficiency. PMID- 27682843 TI - Epidemiology and outcomes of acute kidney injury in elderly chinese patients: a subgroup analysis from the EACH study. AB - BACKGROUND: Information on acute kidney injury (AKI) in elderly hospitalized patients is limited. This study aims to assess the incidence, risk factors and outcomes of AKI in elderly Chinese patients. METHOD: The Epidemiology of AKI in Chinese Hospitalized adults (EACH) study is a multicenter, retrospective cohort study conducted in nine regional central hospitals across China. Patients aged more than 65 years were selected from the EACH study for this analysis. A novel approach with adjustment for frequency of serum creatinine was used to estimate the incidence of AKI in elderly patients. In-hospital outcomes, including mortality, renal recovery, length of stay and daily cost of elderly patients, were analyzed and compared with outcomes in younger patients. RESULTS: Of 144,232 adult patients in the EACH study, 42,737 (29.63 %) patients were 65 years or older, including 9773 very elderly patients (>=80 years old). The incidence of AKI was 15.44 % in patients 65-79 years old (community-acquired (CA) AKI of 3.89 % and hospital-acquired (HA) AKI of 11.55 %) and 22.22 % in the very elderly group (CA-AKI of 6.58 % and HA-AKI of 15.64 %). The mortality rate of AKI was 10.3 % in patients aged from 65 to 80 and 19.6 % in patients older than 80 years. AKI incidence, in-hospital mortality, percentage of patients requiring dialysis and percentage without renal recovery were higher in elderly patients than in younger patients. CONCLUSION: The incidence of AKI in elderly Chinese hospitalized patients is high, which becomes a substantial burden on medical care in China. PMID- 27682845 TI - Fossil Carder Bee's Nest from the Hominin Locality of Taung, South Africa. AB - The Buxton-Norlim Limeworks southwest of Taung, South Africa, is renowned for the discovery of the first Australopithecus africanus fossil, the 'Taung Child'. The hominin was recovered from a distinctive pink calcrete that contains an abundance of invertebrate ichnofauna belonging to the Coprinisphaera ichnofacies. Here we describe the first fossil bee's nest, attributed to the ichnogenus Celliforma, from the Plio-Pleistocene of Africa. Petrographic examination of a cell lining revealed the preservation of an intricate organic matrix lined with the calcitic casts of numerous plant trichomes-a nesting behaviour unique to the modern-day carder bees (Anthidiini). The presence of Celliforma considered alongside several other recorded ichnofossils can be indicative of a dry, savannah environment, in agreement with recent work on the palaeoenvironment of Plio-Pleistocene southern Africa. Moreover, the occurrence of ground-nesting bees provides further evidence that the pink calcrete deposits are of pedogenic origin, rather than speleogenic origin as has previously been assumed. This study demonstrates the potential value of insect trace fossils as palaeoenvironmental indicators. PMID- 27682846 TI - Calculated conjugated payload from immunoassay and LC-MS intact protein analysis measurements of antibody-drug conjugate. AB - AIM: Complex nature of bioconjugates require multiple bioanalytical approaches to support PK and absorption, distribution, metabolism and excretion characterization. For antibody-drug conjugate (ADC) bioanalysis both LC-MS and ligand-binding assays (LBAs) are employed. RESULTS: A method consisting of immunocapture extraction of ADC from biomatrices followed by LC-MS analysis of light and heavy chain is described. Drug antibody ratio (DAR) profiles of ADC Tras-mcVC-PF06380101 dosed at 0.3, 1 and 3 mg/kg in Sprague Dawley rats were obtained. Combined with total antibody (monoclonal antibody) measurement by LBA, conjugated payload concentration was calculated. CONCLUSION: PK profiles from LBA, ADC and calculated conjugated payload (DAR * monoclonal antibody) were in good agreement. We present a new tool for PK assessment of ADCs while also exploring ADC metabolism and DAR sensitivity of LBA ADC assay. PMID- 27682847 TI - Quantification of biofilm formation on silicone intranasal splints: An in vitro study. AB - OBJECTIVES: Biofilms are associated with persistent infections and resistant to conventional therapeutic strategies. The aim of this study was to investigate the quantity of biofilm produced on silicone intranasal splints. METHODS: Quantity of biofilm formation on silicone splints (SS) was tested on 15 strains of Staphylococcus aureus and Moraxella catarrhalis, respectively. Antimicrobial susceptibility testing was performed in accordance with European Committee on Antimicrobial Susceptibility Testing recommendations. RESULTS: All tested strains formed different amounts of biofilm on SS: 66.7% S. aureus and 93.3% M. catarrhalis were weak biofilm producers and 33.3% S. aureus and 6.7% M. catarrhalis were moderate biofilm producers. S. aureus formed significantly higher quantity of biofilm compared with M. catarrhalis (p < 0.05). Multidrug resistant S. aureus produced significantly higher amount of biofilm compared with non-multidrug resistant strains (p < 0.05). CONCLUSION: Quantity of biofilm on SS is highly dependent on bacterial species and their resistance patterns. Future studies are needed to ascertain another therapeutic option for prophylaxis prior to SS placement. PMID- 27682848 TI - DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis. AB - Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4+ (nTh) and CD8+ (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM. PMID- 27682849 TI - Banana fruits affected by Fusarium post-harvest disease as source of human fusariosis. PMID- 27682851 TI - Presumed LRP1-targeting transport peptide delivers beta-secretase inhibitor to neurons in vitro with limited efficiency. AB - Interfering with the activity of beta-secretase to reduce the production of Abeta peptides is a conceivable therapeutic strategy for Alzheimer's disease. However, the development of efficient yet safe inhibitors is hampered by secondary effects, usually linked to the indiscriminate inhibition of other substrates' processing by the targeted enzyme. Based on the spatial compartmentalization of the cleavage of the amyloid precursor protein by beta-secretase, we hypothesized that by exploiting the endocytosis receptor low-density lipoprotein receptor related protein it would be possible to direct an otherwise cell-impermeable inhibitor to the endosomes of neurons, boosting the drug's efficacy and importantly, sparing the off-target effects. We used the transport peptide Angiopep to build an endocytosis-competent conjugate and found that although the peptide facilitated the inhibitor's internalization into neurons and delivered it to the endosomes, the delivery was not efficient enough to potently reduce beta secretase activity at the cellular level. This is likely connected to the finding that in the cell lines we used, Angiopep's internalization was not mediated by its presumed receptor to a significant extent. Additionally, Angiopep exploited different internalization mechanisms when applied alone or when conjugated to the inhibitor, highlighting the impact that drug conjugation can have on transport peptides. PMID- 27682853 TI - Mandating influenza vaccinations for health care workers: analysing opportunities for policy change using Kingdon's agenda setting framework. AB - BACKGROUND: The consequences of annual influenza outbreaks are often underestimated by the general public. Influenza poses a serious public health threat around the world, particularly for the most vulnerable populations. Fortunately, vaccination can mitigate the negative effects of this common infectious disease. Although inoculating frontline health care workers (HCWs) helps minimize disease transmission, some HCWs continue to resist participating in voluntary immunization programs. A potential solution to this problem is government-mandated vaccination for HCWs; however, in practice, there are substantial barriers to the adoption of such policies. The purpose of this paper is to identify the likelihood of adopting a policy for mandatory immunization of HCWs in Ontario based on a historical review of barriers to the agenda setting process. METHODS: Documents from secondary data sources were analysed using Kingdon's agenda setting framework of three converging streams leading to windows of opportunity for possible policy adoption. RESULTS: The problems, politics, and policies streams of Kingdon's framework have converged and diverged repeatedly over an extended period (policy windows have opened and closed several times). In each instance, a technically feasible solution was available. However, despite the evidence supporting the value of HCW immunization, alignment of the three agenda setting streams occurred for very short periods of time, during which, opposition lobby groups reacted, making the proposed solution less politically acceptable. CONCLUSIONS: Prior to the adoption of any new policies, issues must reach a government's decision agenda. Based on Kingdon's agenda setting framework, this only occurs when there is alignment of the problems, politics, and policies streams. Understanding this process makes it easier to predict the likelihood of a policy being adopted, and ultimately implemented. Such learning may be applied to policy issues in other jurisdictions. In the case of mandatory influenza vaccinations for HCWs in Ontario, it seems highly unlikely that a new policy will be adopted until perception of the problem's importance is sufficient to overcome the political opposition to implementing a solution and thus, create a window of opportunity that is open long enough to support change. PMID- 27682852 TI - The Process of Retinal Vascularization after Anti-VEGF Treatment in Retinopathy of Prematurity: A Comparison Study between Ranibizumab and Bevacizumab. AB - PURPOSE: To compare the effects on the process of retinal vascularization of intravitreal ranibizumab (IVR) and intravitreal bevacizumab (IVB) in the treatment of severe retinopathy of prematurity. METHODS: The present study is a bi-centered retrospective study. While 44 eyes of 22 patients in group 1 were applied 0.625 mg bevacizumab, 46 eyes of 23 patients in group 2 were applied 0.25 mg ranibizumab. Retinal vascularization was evaluated clinically. RESULTS: The mean time for completion of vascularization was found to be postmenstrual 55.93 +/- 4.13 weeks in group 1 and 56.30 +/- 4.30 weeks in group 2. There were significant differences in the recurrence prevalence between the two groups. The prevalence of recurrence was found to be significantly higher in the ranibizumab group than in the bevacizumab group (p = 0.023). CONCLUSIONS: The study showed that after IVR or IVB treatment, vascularization could be completed with delay; there were no differences in this delay time between the ranibizumab and bevacizumab groups. Besides, avascular areas may remain in the peripheral retina, and additional treatment may be necessary after IVB or IVR treatment. When the treatment was applied as monotherapy, more recurrence was observed in the ranibizumab group. PMID- 27682854 TI - Cascade Reactions of Nitrones and Allenes for the Synthesis of Indole Derivatives. AB - Cascade reactions involving nitrones and allenes are known to facilitate the rapid synthesis of several indole derivatives. The chemoselectivity of these complicated transformations can be influenced by substrate functionalization, reaction conditions, and catalyst control. While seminal studies established primary reactivity patterns, recent work has illustrated the impact of these cascade reactions for creating diverse libraries, increased the breadth of these methods with facilitated access to challenging nitrones, and shown that these transformations can be controlled by asymmetric catalysis. PMID- 27682855 TI - Cryoballoon Ablation for Atrial Fibrillation: Double Jeopardy? PMID- 27682856 TI - Multiple clear cell acanthomas and a sebaceous lymphadenoma presenting in a patient with Cowden syndrome - a case report. AB - Cowden syndrome (CS) is an uncommon autosomal dominant multiorgan/system genodermatosis. It is characterized by the development of multiple hamartomas of endodermal, mesodermal and ectodermal origin, an increased lifetime risk of breast, thyroid, endometrial and other cancers and an identifiable germline mutation. Mucocutaneous hamartomas are the most common lesions seen and mainly include facial trichilemmomas, oral mucosal papillomas and benign acral keratoses. Herein, we report a case of a 63-year-old Caucasian male with a long established diagnosis of CS and history of thyroid cancer, colonic polyps, and innumerable trichilemmomas, seborrheic keratoses, squamous papillomas and non melanoma skin cancers excised in the past. He presented in four separate occasions with small skin-colored papulonodular lesions that upon excision revealed to be clear cell acanthomas. He also developed a tumor in the preauricular area that was completely resected and was found to be a sebaceous lymphadenoma (SLA) of the parotid gland. This is to our knowledge, the second report of clear cell acanthoma and also the second reported case of SLA in a patient with CS. PMID- 27682857 TI - Mediating patienthood-from an ethics of to an ethics with technology. AB - The changes that happen to healthcare services after the implementation of new assistive healthcare technologies (also called 'welfare technology' in the Nordic countries) concern more than increased efficiency and reducing healthcare expenditure. Of particular interest from an ethical point of view are the manners in which technologies shape the roles and identities of care receivers and healthcare personnel. The notion of 'patienthood' is explored in this paper as something that is both challenged by new technologies, and as something that is opened up for active and potentially positive reshaping when care receivers support their illness or frailty with assistive healthcare technologies. This dual effect of technologies (as both challenge and opportunity) requires a rethinking of ethics of technologies, which for most part have been preoccupied with ethical issues prior to the implementation of a new technology into a healthcare service. Ethics of technology should also contribute to the concrete efforts of care receivers to establish something approximating a 'good patienthood' in relation to a new technology, making it opportune to dub it, instead, an ethics with technology. This paper explores how assistive healthcare technologies impact on care receivers and the care situation, and in relation to the notion of patienthood, before turning to what this implies for an ethics that has as its goal to support care receivers to reach a life with the technology that is in line with their own notions of well-being and a good life. PMID- 27682858 TI - Estrogenic Receptor-Functionalized Magnetite Nanoparticles for Rapid Separation of Phytoestrogens in Plant Extracts. AB - With growing interests of phytoestrogens, many natural phytochemicals extracted from diverse plant species have been explored for their estrogenic-like activities and potential applications. In this work, a simple and rapid separation of phytoestrogenic compounds from crude plant extracts was purposed using magnetic nanoparticles (MNPs) of Fe3O4 immobilized with the ligand-binding domain (LBD) of estrogen receptor alpha (ERalpha). The recombinant LBD-ERalpha peptide of 40 kDa was produced and subsequently covalently linked to MNPs. One milligram of the LBD-ERalpha-immobilized MNPs demonstrated a specific binding to the standard 17beta-estradiol (E2) of 3.37 nmol and 91.3-100 % of the bound E2 were subsequently recovered. LBD-ERalpha-immobilized MNPs could separate phytoestrogens of 4.6 nmol E2-equivalent activity from a 1-mg crude extract of Asparagus racemosus. The produced MNPs showed no separation yield when were applied to the negative controls, the crude extract of radish (Raphanus sativus), and the standard progesterone (P4). Thin-layer chromatography demonstrated a single phytochemical band of the separated phytoestrogens, which exhibited the activity to promote MCF-7 cell proliferation at 4.7 folds greater than the crude A. racemosus extract. The results of this work demonstrated a simple method to specifically separate phytoestrogens from crude plant extracts via the LBD ERalpha-immobilized MNPs. PMID- 27682859 TI - Vine Trimming Shoots as Substrate for Ferulic Acid Esterases Production. AB - Ferulic acid esterases (FAE) possess a large variety of biotechnological applications mainly based on their ability to release ferulic acid from lignocellulosic matrixes. The use of vine trimming shoots (VTS), an agricultural waste, as substrate for the generation of this kind of esterases represents an attractive alternative to change the consideration of VTS from residue to resource. Furthermore, xylanase, cellobiase, and cellulase activities were quantified. Six microorganisms were screened for FAE production by solid-state fermentation, and the effects of the additional supplementation and substrate size were also tested. Finally, the process was scaled-up to a horizontal bioreactor where the influence of aeration in enzymatic activities was evaluated. Thus, the optimal FAE activity (0.44 U/g dry VTS) was attained by Aspergillus terreus CECT 2808, in non-additional supplementation media, using the larger particles size of substrate (<= 5 mm) and at a flow rate of 0.7 L/min. PMID- 27682860 TI - Addenbrooke's cognitive examination III: diagnostic utility for mild cognitive impairment and dementia and correlation with standardized neuropsychological tests. AB - BACKGROUND: Addenbrooke's Cognitive Examination III (ACE-III) is a screening test that was recently validated for diagnosing dementia. Since it assesses attention, language, memory, fluency, and visuospatial function separately, it may also be useful for general neuropsychological assessments. The aim of this study was to analyze the tool's ability to detect early stages of Alzheimer's disease and to examine the correlation between ACE-III scores and scores on standardized neuropsychological tests. METHODS: Our study included 200 participants categorized as follows: 25 healthy controls, 48 individuals with subjective memory complaints, 47 patients with amnestic mild cognitive impairment and 47 mild Alzheimer's disease, and 33 patients with other neurodegenerative diseases. RESULTS: The ACE-III memory and language domains were highly correlated with the neuropsychological tests specific to those domains (Pearson correlation coefficient of 0.806 for total delayed recall on the Free and Cued Selective Reminding Test vs. 0.744 on the Boston Naming Test). ACE-III scores discriminated between controls and patients with amnestic mild cognitive impairment (AUC: 0.906), and between controls and patients with mild Alzheimer's disease (AUC: 0.978). CONCLUSION: Our results suggest that ACE-III is a useful neuropsychological test for assessing the cognitive domains of attention, language, memory, and visuospatial function. It also enables detection of Alzheimer's disease in early stages. PMID- 27682861 TI - Optimal Behavior is Easier to Learn than the Truth. AB - We consider a reinforcement learning setting where the learner is given a set of possible models containing the true model. While there are algorithms that are able to successfully learn optimal behavior in this setting, they do so without trying to identify the underlying true model. Indeed, we show that there are cases in which the attempt to find the true model is doomed to failure. PMID- 27682862 TI - Cellular mysteries of plant sex. PMID- 27682863 TI - Chemokine CXCL1 may serve as a potential molecular target for hepatocellular carcinoma. AB - The purpose of this study was to screen for changes in chemokine and chemokine related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated. Finally, total serum samples were collected from HCC patients with HBV/cirrhosis (n = 16) or liver cirrhosis (n = 16) and from healthy controls (n = 16). The serum mRNA and protein expression levels of CXCL1 in primary liver cancer patients were detected by qRT-PCR and western blot analysis, respectively. Several genes were up regulated in tumor tissues during the progression period, including CXCL1, CXCL2, CXCL3, and IL-1beta, while CXCR1 expression was down-regulated. CBRH-7919 cells carrying CXCL1 siRNA resulted in decreased tumor growth in nude mice. The differences in serum CXCL1 mRNA and protein levels among the HCC, hepatic sclerosis (HS), and control groups were significant (P < 0.001). The mRNA and protein levels of CXCL1 in the HCC group were up-regulated compared with the HS group or the control group (P < 0.001). Several chemokine genes were identified that might play important roles in the tumor microenvironment of HCC. These results provide new insights into human HCC and may ultimately facilitate early HCC diagnosis and lead to the discovery of innovative therapeutic approaches for HCC. PMID- 27682866 TI - Editorial (Thematic Issue: Medicinal Chemistry Applied to Natural Products in Neglected Drug Discovery). PMID- 27682865 TI - Increased expression of ATP binding cassette transporter genes following exposure of Haemonchus contortus larvae to a high concentration of monepantel in vitro. AB - BACKGROUND: There is some evidence that ATP binding cassette (ABC) transporters play a role in resistance to anthelmintics, particularly against macrocyclic lactones. Some anthelmintics, including ivermectin (IVM), have been shown to induce transcription of multiple ABC transporters in nematodes; however, the effects of monepantel (MPL) on transcription of these transporter genes has not been studied. METHODS: Larvae of two MPL-susceptible isolates of Haemonchus contortus were exposed to MPL at two concentrations (2.5 and 250 MUg/ml) for periods of 3, 6 and 24 h. Transcription levels of sixteen ABC transporter genes were measured at the end of the incubation periods. The consequences of MPL exposure were examined by measuring rhodamine-123 efflux from the larvae, and their sensitivity to subsequent treatment with IVM or levamisole. RESULTS: Multiple ABC transporter genes showed significantly higher transcription in both worm isolates following exposure to MPL at 250 MUg/ml for 3, 6 or 24 h, particularly the P-glycoprotein (P-gp) genes pgp-11, pgp-12 and pgp-14. Of these, only pgp-11 maintained the elevated levels 24 h after the end of the drug exposure period. In contrast, there was only a single instance of low-level upregulation as a result of exposure to MPL at 2.5 MUg/ml. Larvae exposed to MPL at 250 MUg/ml showed an increased efflux of rhodamine-123 and a proportion of the larval population showed an ability to subsequently tolerate higher concentrations of IVM in migration assays. There was no increased tolerance to IVM following pre-exposure to MPL at 2.5 MUg/ml. CONCLUSIONS: Exposure of H. contortus larvae to 250 MUg/ml MPL results in increased transcription of multiple transporter genes and increased R-123 efflux. The subsequent ability of a proportion of the larvae to tolerate IVM suggests a protective role of ABC transporters across different chemical entities. However, these observations were only made at a concentration of MPL well above that experienced by parasitic life stages in vivo, and hence their significance remains unclear. PMID- 27682864 TI - Preoperative radiotherapy in the management of retroperitoneal liposarcoma. AB - BACKGROUND: Histological subtype influences both prognosis and patterns of treatment failure in retroperitoneal sarcoma. Previous studies on the efficacy of neoadjuvant radiotherapy (NRT) have incorporated multiple histological types with heterogeneous tumour biology. The survival impact of NRT specifically for patients with retroperitoneal liposarcoma is poorly defined. METHODS: Patients who underwent resection with curative intent for retroperitoneal liposarcoma and who received NRT or surgery alone were identified in the US National Cancer Data Base (2004-2013). Cox regression was used to identify co-variables associated with overall survival. NRT and surgery-alone cohorts were matched 1 : 1 by propensity scores based on the survival hazard on Cox modelling. Overall survival was compared by Kaplan-Meier estimates. RESULTS: A total of 2082 patients with retroperitoneal liposarcoma were identified; 1908 underwent surgery alone and 174 received NRT before surgical resection. Median tumour size was 22.0 cm and 34.9 per cent of tumours were high grade. In the unmatched cohort, NRT was not associated with improved overall survival (chi2 = 3.49, P = 0.062). In the propensity score-matched cohort, NRT was associated with an improvement in survival (median overall survival 129.2 versus 84.3 months; P = 0.046; hazard ratio (HR) 1.54, 95 per cent c.i. 1.01 to 2.36). This effect appeared most pronounced for tumours with adjacent organ invasion (median overall survival not reached versus 63.8 months; P = 0.044; HR 1.79, 1.01 to 3.19). CONCLUSION: NRT improved survival in patients undergoing surgery for retroperitoneal liposarcoma, particularly those with high-risk pathological features. PMID- 27682867 TI - Natural Products as a Source for Antileishmanial and Antitrypanosomal Agents. AB - Natural products are compounds extracted from plants, marine organisms, fungi or bacteria. Many researches for new drugs are based on these natural molecules, mainly by beneficial effects on health, health, efficacy, and therapeutic safety. Leishmaniosis, Chagas disease and African sleeping sickness are neglected diseases caused by the Leishmania and Trypanosoma ssp. parasites. These infections mainly affect population of developing countries; they have different symptoms, and may often lead to death. The therapeutic drugs available to treat these diseases are either obsolete, toxic, or have questionable efficacy, possibly through encountering resistance. Discovery of new, safe, effective, and affordable molecules is urgently needed. Natural organisms, as marine metabolites, alkaloids, flavonoids, steroids, terpene and coumarins provide innumerable molecules with the potential to treat these diseases. This study examines studies of natural bioactive compounds as antileishmanial and antitrypanosomal agents. PMID- 27682869 TI - Diamonds, Digital Health, and Drug Development: Optimizing Combinatorial Nanomedicine. AB - The field of nanomedicine has already seen substantial progress in the clinic, with multiple formulations being evaluated through clinical studies. From poly(lactic-co-glycolic acid) and cyclodextrin-based drug-delivery platforms to metallic nanoparticles for photothermal treatment and imaging, nanotechnology has enabled versatile strategies to treat and to diagnose a wide range of disorders. However, as the field as a whole pushes forward, barriers that have always challenged conventional drug development have already started to impact nanomedicine translation. These include exorbitant costs, substantial time to development, and the uncertainty of achieving major improvements in efficacy or safety. Of note, there has been, until recent advances, a virtual inability to identify optimal drug doses either as monotherapies or components of combination therapy. In this Nano Focus, we assess how the impact of nanotechnology in the clinic can be optimized through systematically designed combinatorial nanotherapy. In addition, we provide a clinical perspective on how a recently unveiled technology platform can substantially alter the landscape of combinatorial nanomedicine, drug development, as well as conventional drug development. PMID- 27682868 TI - Financial incentives to improve adherence to antipsychotic maintenance medication in non-adherent patients: a cluster randomised controlled trial. AB - BACKGROUND: Poor adherence to long-term antipsychotic injectable (LAI) medication in patients with psychotic disorders is associated with a range of negative outcomes. No psychosocial intervention has been found to be consistently effective in improving adherence. OBJECTIVES: To test whether or not offering financial incentives is effective and cost-effective in improving adherence and to explore patient and clinician experiences with such incentives. DESIGN: A cluster randomised controlled trial with economic and nested qualitative evaluation. The intervention period lasted for 12 months with 24 months' follow up. The unit of randomisation was mental health teams in the community. SETTING: Community teams in secondary mental health care. PARTICIPANTS: Patients with a diagnosis of schizophrenia, schizoaffective psychosis or bipolar illness, receiving <= 75% of their prescribed LAI medication. In total, 73 teams with 141 patients (intervention n = 78 and control n = 63) were included. INTERVENTIONS: Participants in the intervention group received L15 for each LAI medication. Patients in the control group received treatment as usual. MAIN OUTCOME MEASURES: PRIMARY OUTCOME: adherence to LAI medication (the percentage of received out of those prescribed). SECONDARY OUTCOMES: percentage of patients with at least 95% adherence; clinical global improvement; subjective quality of life; satisfaction with medication; hospitalisation; adverse events; and costs. Qualitative evaluation: semistructured interviews with patients in the intervention group and their clinicians. RESULTS: PRIMARY OUTCOME: outcome data were available for 131 patients. Baseline adherence was 69% in the intervention group and 67% in the control group. During the intervention period, adherence was significantly higher in the intervention group than in the control group (85% vs. 71%) [adjusted mean difference 11.5%, 95% confidence interval (CI) 3.9% to 19.0%; p = 0.003]. Secondary outcome: patients in the intervention group showed statistically significant improvement in adherence of at least 95% (adjusted odds ratio 8.21, 95% CI 2.00 to 33.67; p = 0.003) and subjective quality of life (difference in means 0.71, 95% CI 0.26 to 1.15; p = 0.002). Follow-ups: after incentives stopped, adherence did not differ significantly between groups, neither during the first 6 months (adjusted difference in means -7.4%, 95% CI -17.0% to 2.1%; p = 0.175) nor during the period from month 7 to month 24 (difference in means 5.7%, 95% CI -13.1% to 1.7%; p = 0.130). Cost-effectiveness: the average costs of the financial incentives was L303. Overall costs per patient were somewhat higher in the intervention group, but the difference was not significant. Semistructured interviews: the majority of patients and clinicians reported positive experiences with the incentives beyond their monetary value. These included improvement in the therapeutic relationship. The majority of both patients and clinicians perceived no negative impact after the intervention was stopped after 1 year. CONCLUSIONS: Financial incentives are effective in improving adherence to LAI medication. Health-care costs (including costs of the financial incentive) are unlikely to be increased substantially by this intervention. Once the incentives stop, the advantage is not maintained. The experiences of both patients and clinicians are largely, but not exclusively, positive. Whether or not financial incentives are effective for patients with more favourable background, those on oral mediation or for shorter or longer time periods remains unknown. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77769281. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 70. See the NIHR Journals Library website for further project information. PMID- 27682870 TI - Atmospheric Chemistry of Criegee Intermediates: Unimolecular Reactions and Reactions with Water. AB - Criegee intermediates are produced in the ozonolysis of unsaturated hydrocarbons in the troposphere, and understanding their fate is a prerequisite to modeling climate-controlling atmospheric aerosol formation. Although some experimental and theoretical rate data are available, they are incomplete and partially inconsistent, and they do not cover the tropospheric temperature range. Here, we report quantum chemical rate constants for the reactions of stabilized formaldehyde oxide (CH2OO) and acetaldehyde oxide (syn-CH3CHOO and anti-CH3CHOO) with H2O and for their unimolecular reactions. Our results are obtained by combining post-CCSD(T) electronic structure benchmarks, validated density functional theory potential energy surfaces, and multipath variational transition state theory with multidimensional tunneling, coupled-torsions anharmonicity, and high-frequency anharmonicity. We consider two different types of reaction mechanisms for the bimolecular reactions, namely, (i) addition-coupled hydrogen transfer and (ii) double hydrogen atom transfer (DHAT). First, we show that the MN15-L exchange-correlation functional has kJ/mol accuracy for the CH2OO + H2O and syn-CH3CHOO + H2O reactions. Then we show that, due to tunneling, the DHAT mechanism is especially important in the syn-CH3CHOO + H2O reaction. We show that the dominant pathways for reactions of Criegee intermediates depend on altitude. The results we obtain eliminate the discrepancy between experiment and theory under those conditions where experimental results are available, and we make predictions for the full range of temperatures and pressures encountered in the troposphere and stratosphere. The present results are an important cog in clarifying the atmospheric fate and oxidation processes of Criegee intermediates, and they also show how theoretical methods can provide reliable rate data for complex atmospheric processes. PMID- 27682871 TI - Role of Dicer as a prognostic predictor for survival in cancer patients: a systematic review with a meta-analysis. AB - OBJECTIVE: The role of Dicer in the prognosis of cancer patients remains controversial. This systematic review is attempted to assess the influence of Dicer as a prognostic predictor for survival in diverse types of cancers. METHODS: Studies were selected as candidates if they published an independent evaluation of Dicer expression level together with the correlation with prognosis in cancers. Random-effect model was applied in this meta-analysis. Heterogeneity between studies was assessed by Q-statistic with P < 0.10 to be statistically significant. Publication bias was investigated using funnel plot and test with Begg's and Egger's test. P < 0.05 was regarded as statistically significant. RESULTS: 24 of 44 articles revealed low Dicer status as a predictor of poor prognosis. The aggregate result of overall survival (OS) indicated that low Dicer expression level resulted in poor clinical outcomes, and subgroup of IHC and RT PCR method both revealed the same result. Overall analysis of progression-free survival (PFS) showed the same result as OS, and both the two subgroups divided by laboratory method revealed positive results. Subgroup analysis by tumor types showed low dicer levels were associated with poor prognosis in ovarian cancer (HR = 1.93, 95% CI: 1.19-3.15), otorhinolaryngological tumors (HR = 2.39, 95% CI: 1.70-3.36), hematological malignancies (HR = 2.45, 95% CI: 1.69-3.56) and neuroblastoma (HR = 4.03, 95% CI: 1.91-8.50). CONCLUSION: Low Dicer status was associated with poor prognosis in ovarian cancer, otorhinolaryngological tumors and ematological malignancies. More homogeneous studies with high quality are needed to further confirm our conclusion and make Dicer a useful parameter in clinical application. PMID- 27682872 TI - Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA. AB - Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment).We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B cells expressing regulatory genes may play an important role in the protective immunity against M.tb infection. Our results show that increased activation of B cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response. PMID- 27682873 TI - Haploinsufficiency in tumor predisposition syndromes: altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation. AB - Tumor suppressor genes and their effector pathways have been identified for many dominantly heritable cancers, enabling efforts to intervene early in the course of disease. Our approach on the subject of early intervention was to investigate gene expression patterns of morphologically normal "one-hit" cells before they become hemizygous or homozygous for the inherited mutant gene which is usually required for tumor formation. Here, we studied histologically non-transformed renal epithelial cells from patients with inherited disorders that predispose to renal tumors, including von Hippel-Lindau (VHL) disease and Tuberous Sclerosis (TSC). As controls, we studied histologically normal cells from non-cancerous renal epithelium of patients with sporadic clear cell renal cell carcinoma (ccRCC). Gene expression analyses of VHLmut/wt or TSC1/2mut/wt versus wild-type (WT) cells revealed transcriptomic alterations previously implicated in the transition to precancerous renal lesions. For example, the gene expression changes in VHLmut/wt cells were consistent with activation of the hypoxia response, associated, in part, with the "Warburg effect". Knockdown of any remaining VHL mRNA using shRNA induced secondary expression changes, such as activation of NFkappaB and interferon pathways, that are fundamentally important in the development of RCC. We posit that this is a general pattern of hereditary cancer predisposition, wherein haploinsufficiency for VHL or TSC1/2, or potentially other tumor susceptibility genes, is sufficient to promote development of early lesions, while cancer results from inactivation of the remaining normal allele. The gene expression changes identified here are related to the metabolic basis of renal cancer and may constitute suitable targets for early intervention. PMID- 27682874 TI - Elevated level of interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3. AB - IL-35 is a novel heterodimeric and inhibitory cytokine, composed of interleukin 12 subunit alpha (P35) and Epstein-Barr virus -induced gene 3 (EBI3). IL-35 has been reported to be produced by a range of cell types, especially regulatory T cells, and to exert immunosuppressive effects via the STATx signaling pathway. In this study, we demonstrated that IL-35 expression was elevated in both serum and tumors in patients with colorectal cancer. IL-35 mainly expressed in CD4+ T cells in human colorectal cancer tumors and adjacent tissues. Increased IL-35 expression in tumor-adjacent tissues was significantly associated with tumor metastasis. IL-35 inhibited the proliferation of CD4+CD25- T effector cells in vitro in a dose-dependent manner, and its suppression was partially reversed by applying IL-35-neutralizing antibodies. IL-35 treatment activated the phosphorylation of both STAT1 and STAT3 in human CD4+ T cells. Meanwhile, IL-35 induced a positive feedback loop to promote its own production. We observed that Tregs obtained from colorectal cancer patients were capable of inducing more IL 35 production. In addition, EBI3 promoter-driven luciferase activity was higher than that of the mock plasmid after IL-35stimulation. Thus, our study indicates that the high level of IL-35 in colorectal cancer promotes the production of IL 35 via STAT1 and STAT3, which suppresses T cell proliferation and may participate in tumor immunotolerance. PMID- 27682877 TI - Tumour suppressor gene (CDKNA2) status on chromosome 9p in resected renal tissue improves prognosis of localised kidney cancer. AB - BACKGROUND: Genetic alterations on chromosome 9p, including inactivation of the tumour suppressor gene, CDKN2A, result in cellular proliferation and growth of tumours. Our aim was to use microsatellite analysis and fluorescence in situ hybridization (FISH) to characterise the architecture of this region. RESULTS: Seventy-five out of 77 clear cell renal cell cancers (tumour/normal pairs) were interpretable for LOH analysis on chromosome 9p (two tumours were excluded, as all five primers were uninformative). Twenty out of 75 (26.6%) tumours showed LOH in at least one of the five primers employed. Most allelic deletions were detected, telomeric to the CDKN2A region at D9S916, with 11 out of 52 informative tumours (21%) displaying LOH. The LOH in the coding region of CDKN2A, at D9S974 and D9S942, was associated with a higher pT-stage (p = 0.004) and metastasis (p = 0.006, both markers). The rate of chromosome 9p deletion in ccRCC was 44% (35/80 cases) according to FISH. Somatic copy number loss of chromosome 9p was associated with a larger tumour size (p = 0.002), higher pathological tumour stage (p = 0.021), presence of tumour necrosis (p = 0.019) and microvascular invasion (p = 0.032). The cases with copy number loss, loss of heterozygosity and copy number neutral (n = 42) were at a higher risk of cancer-specific death when compared to tumours in category D (n = 32) (Log-rank: p = 0.001). Seventeen patients with localised ccRCC developed recurrence, and fourteen of those showed either LOH or somatic copy number loss at CDKN2A (Log-rank: p = 0.005). Multivariate analysis showed that LOH or copy number loss at CDKN2A retained its independent prognostic effect, improving the predictive accuracy of stage and SSIGN score by concordance Index C from 0.823 to 0.878 (p = 0.001). MATERIALS AND METHODS: Cytogenetics data, microsatellite analysis and FISH were acquired for a cohort of patients undergoing resection for clinically localised renal cancer between January 2001 and December 2005. Five microsatellite markers (D9S916, D9S1814, D9S974, D9S942 and D9S171) assessed loss of heterogeneity (LOH) using DNA samples and in the same cohort FISH analysis was accomplished on tissue microarray slides. The FISH data were scored by two observers blinded to the histological data of the patients. Cytogenetic aberrations were correlated with histological and clinical outcomes by univariate and multivariate analyses using different prognostic models. Disease specific and recurrence free survival based on cytogenetic changes were assessed by Kaplan Meier methods. CONCLUSIONS: A comprehensive cytogenetic analysis using microsatellite analysis and FISH of the CDKN2A region on chromosome 9p improves the predictive accuracy of known prognostic factors in clinically localised renal cell carcinoma undergoing surgical resection. PMID- 27682876 TI - Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-beta/IkappaBalpha/NFkappaB axis. AB - Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFkappaB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFkappaB pathway was stimulated. Pharmacological inhibition of the IKK-beta/IkappaBalpha/NFkappaB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem. PMID- 27682875 TI - Targeting cancer initiating cells by promoting cell differentiation and restoring chemosensitivity via dual inactivation of STAT3 and src activity using an active component of antrodia cinnamomea mycelia. AB - Cancer initiating cells (CICs) represent a subpopulation of cancer cells, which are responsible for tumor growth and resistance to chemotherapy. Herein, we first used a cell-based aldehyde dehydrogenase (ALDH) activity assay to identify that YMGKI-2 (also named as Ergone), an active component purified from Antrodia cinnamomea Mycelia extract (ACME), effectively abrogated the ALDH activity and abolished the CICs in head and neck squamous cell carcinoma cells (HNSCCs). Consequently, YMGKI-2 treatment suppressed self-renewal ability and expression of stemness signature genes (Oct-4 and Nanog) of sphere cells with enriched CICs. Moreover, YMGKI-2 treated sphere cells displayed reduction of CICs properties and promotion of cell differentiation, but not significant cytotoxicity. YMGKI-2 treatment also attenuated the tumorigenicity of HNSCC cells in vivo. Mechanistically, treatment of YMGKI-2 resulted in inactivation of STAT3 and Src. Lastly, combinatorial treatments with YMGKI-2 and standard chemotherapeutic drugs (cisplatin or Fluorouracil) restored the chemosensivity on sphere cells and cisplatin-resistant HNSCC cells. Together, we demonstrate that YMGKI-2 treatment effectively induces differentiation and reduces tumorigenicity of CICs. Further, combined treatment of YMGKI-2 and conventional chemotherapy can overcome chemoresistance. These results suggest that YMGKI-2 treatment may be used to improve future clinical responses in head and neck cancer treatment through targeting CICs. PMID- 27682879 TI - Supraclavicular and/or celiac lymph node metastases from thoracic esophageal squamous cell carcinoma did not compromise survival following neoadjuvant chemoradiotherapy and surgery. AB - This study is to evaluate the prognostic significance of supraclavicular and/or celiac lymph node (LN) metastases in locally advanced thoracic esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiotherapy (NACRT) and surgery. Among the total 199 patients, 75 (37.7%) had supraclavicular and/or celiac LN metastasis. Surgery was performed following NACRT in 168 patients (84.4%). After the median 18.7 (1.0-147.2) months' follow up, 2-year rates of progression-free survival (PFS) and overall survival (OS) in all patients were 48.1% and 65.7%, respectively. In multivariate analyses, negative surgical margin (p < 0.001), ypT0 stage (p = 0.004), and ypN0 stage (p = 0.020) were significantly favorable factors for PFS, and negative surgical margin (p < 0.001) was the only significantly favorable factor for OS. Metastasis to the supraclavicular and/or celiac LNs was significant factor neither for PFS (p = 0.311) nor OS (p = 0.515). Supraclavicular and/or celiac LN metastasis did not compromise the clinical outcomes following NACRT and surgery. PMID- 27682878 TI - The C-terminal domain of connexin43 modulates cartilage structure via chondrocyte phenotypic changes. AB - Chondrocytes in cartilage and bone cells population express connexin43 (Cx43) and gap junction intercellular communication (GJIC) is essential to synchronize cells for coordinated electrical, mechanical, metabolic and chemical communication in both tissues. Reduced Cx43 connectivity decreases chondrocyte differentiation and defective Cx43 causes skeletal defects. The carboxy terminal domain (CTD) of Cx43 is located in the cytoplasmic side and is key for protein functions. Here we demonstrated that chondrocytes from the CTD-deficient mice, K258stop/Cx43KO and K258stop/K258stop, have reduced GJIC, increased rates of proliferation and reduced expression of collagen type II and proteoglycans. We observed that CTD truncated mice were significantly smaller in size. Together these results demonstrated that the deletion of the CTD negatively impacts cartilage structure and normal chondrocyte phenotype. These findings suggest that the proteolytic cleavage of the CTD under pathological conditions, such as under the activation of metalloproteinases during tissue injury or inflammation, may account for the deleterious effects of Cx43 in cartilage and bone disorders such as osteoarthritis. PMID- 27682881 TI - Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers. AB - Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure-activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC50) typically below 5 nM, at least an order of magnitude better than the EC50 values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC50 > 400 MUM) and high ability to induce photodamage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT. PMID- 27682880 TI - Changes in the cellular immune system and circulating inflammatory markers of stroke patients. AB - This study was designed to investigate dynamic changes in the cellular immune system and circulating inflammatory markers after ischemic stroke. Blood was collected from 96 patients and 99 age-matched control subjects for detection of lymphocyte subpopulations and inflammatory markers. We observed decreases in B cells, Th cells, cytotoxic T cells, and NK cells and an increase in regulatory T (Treg) cells in stroke patients on days 1, 3, and 7. Serum levels of TNF-alpha, C reactive protein (CRP), IL-4, IL-6, IL-10, IL-17, IL-23, and TGF-beta increased, whereas serum level of IFN-gamma decreased at all time points after stroke. Stroke patients with infection exhibited a similar tendency toward changes in some lymphocyte subpopulations and inflammatory markers as stroke patients without infection. After controlling for NIH Stroke Scale (NIHSS), we observed no differences in lymphocyte subpopulations between patients with anterior circulation stroke and those with posterior circulation stroke at any time point. The splenic volume correlated positively with the percentages of B cells, Th cells, and cytotoxic T cells, but negatively with Treg cells on day 3 after stroke. Infections were associated with splenic volume, leukocyte counts, percentage of Treg cells, and serum levels of CRP, IL-10, and IFN-gamma on day 3. Lesion volume correlated positively with CRP, IL-6, and IL-23, but negatively with IFN-gamma on day 3. The NIHSS showed a positive relation with IL-6 and IL-10 on day 3. Ischemic stroke has a profound effect on the systemic immune system that might explain the increased susceptibility of stroke patients to infection. PMID- 27682883 TI - Distribution of Estimated 10-Year Risk of Recurrent Vascular Events and Residual Risk in a Secondary Prevention Population. AB - BACKGROUND: Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets. METHODS: The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents. RESULTS: The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%-28%), varying from <10% in 18% to >30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be <10% in 47% and >30% in 9% of the patients (median, 11%; interquartile range, 7%-17%). CONCLUSIONS: Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk <10%. These data suggest that even with optimal treatment, many patients with vascular disease will remain at >20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need. PMID- 27682882 TI - Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations. AB - Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. The extensive use of antifungal prophylaxis has reduced the infections from yeasts (e.g., candidemia) even though they are still associated with high mortality rates. This paper analyzes concurrent multiple predisposing factors that could favor the onset of fungal infections. Although neutropenia is common to almost all hematologic patients, other factors play a key role in specific patients, in particular in patients with AML or allogeneic HSCT recipients. Defining those patients at higher risk of IFIs may help to design the most appropriate diagnostic work-up and antifungal strategy. PMID- 27682884 TI - Risk Prediction: Are We There Yet? PMID- 27682887 TI - ? PMID- 27682885 TI - Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China). AB - BACKGROUND: The accurate assessment of individual risk can be of great value to guiding and facilitating the prevention of atherosclerotic cardiovascular disease (ASCVD). However, prediction models in common use were formulated primarily in white populations. The China-PAR project (Prediction for ASCVD Risk in China) is aimed at developing and validating 10-year risk prediction equations for ASCVD from 4 contemporary Chinese cohorts. METHODS: Two prospective studies followed up together with a unified protocol were used as the derivation cohort to develop 10 year ASCVD risk equations in 21 320 Chinese participants. The external validation was evaluated in 2 independent Chinese cohorts with 14 123 and 70 838 participants. Furthermore, model performance was compared with the Pooled Cohort Equations reported in the American College of Cardiology/American Heart Association guideline. RESULTS: Over 12 years of follow-up in the derivation cohort with 21 320 Chinese participants, 1048 subjects developed a first ASCVD event. Sex-specific equations had C statistics of 0.794 (95% confidence interval, 0.775-0.814) for men and 0.811 (95% confidence interval, 0.787-0.835) for women. The predicted rates were similar to the observed rates, as indicated by a calibration chi2 of 13.1 for men (P=0.16) and 12.8 for women (P=0.17). Good internal and external validations of our equations were achieved in subsequent analyses. Compared with the Chinese equations, the Pooled Cohort Equations had lower C statistics and much higher calibration chi2 values in men. CONCLUSIONS: Our project developed effective tools with good performance for 10-year ASCVD risk prediction among a Chinese population that will help to improve the primary prevention and management of cardiovascular disease. PMID- 27682888 TI - miR-548b inhibits the proliferation and invasion of malignant gliomas by targeting metastasis tumor-associated protein-2. AB - microRNAs (miRNAs) play important roles in cancer development and progression. In this study, we explored the expression and biological roles of miR-548b in human gliomas. The expression of miR-548b in human glioma tissues and cell lines was examined. Gain-of-function experiments were conducted to determine the roles of miR-548b in glioma cell growth, invasiveness, and tumorigenesis. Bioinformatic analysis and luciferase reporter assays were performed to identify direct target genes for miR-548b. miR-548b was underexpressed in human glioma tissues and cell lines. Re-expression of miR-548b significantly inhibited the proliferation and colony formation of U87 and U373 glioma cells. Enforced expression of miR-548b significantly impaired the invasiveness of glioma cells. Notably, metastasis tumor-associated protein-2 (MTA2) was a direct target of miR-548b. Overexpression of miR-548b negatively regulated endogenous MTA2 expression in U87 cells. Rescue experiments with an MTA2 construct lacking the 3'-untranslated region showed that enforced expression of MTA2 significantly restored cell proliferation and invasion in miR-548b-overexpressing cells. In-vivo studies confirmed that miR 548b overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of MTA2. In conclusion, miR-548b exerts its tumor-suppressive activity in glioma through repression of MTA2. Restoration of miR-548b may have therapeutic potential in glioma. PMID- 27682889 TI - Culture growth of testate amoebae under different silicon concentrations. AB - Testate amoebae with self-secreted siliceous shell platelets ("idiosomes") play an important role in terrestrial silicon (Si) cycles. In this context, Si dependent culture growth dynamics of idiosomic testate amoebae are of interest. Clonal cultures of idiosomic testate amoebae were analyzed under three different Si concentrations: low (50MUmolL-1), moderate/site-specific (150MUmolL-1) and high Si supply (500MUmolL-1). Food (Saccharomyces cerevisiae) was provided in surplus. (i) Shell size of four different clones of idiosomic testate amoebae either decreased (Trinema galeata, Euglypha filifera cf.), increased (E. rotunda cf.), or did not change (E. rotunda) under the lowest Si concentration (50MUmolSiL-1). (ii) Culture growth of idiosomic Euglypha rotunda was dependent on Si concentration. The more Si available in the culture medium, the earlier the entry into exponential growth phase. (iii) Culture growth of idiosomic Euglypha rotunda was dependent on origin of inoculum. Amoebae previously cultured under a moderate Si concentration revealed highest sustainability in consecutive cultures. Amoebae derived from cultures with high Si concentrations showed rapid culture growth which finished early in consecutive cultures. (iv) Si (diluted in the culture medium) was absorbed by amoebae and fixed in the amoeba shells resulting in decreased Si concentrations. PMID- 27682890 TI - Relationships between environmental conditions and the morphological variability of planktonic testate amoeba in four neotropical floodplains. AB - Planktonic testate amoebae in floodplains exhibit a broad-range of morphological variability. The variation size is already known, but it is necessary to know how this is for morphological variables. This study aimed to identify the relationships between testate amoebae morphology and environmental factors in four neotropical floodplains. We conducted detailed morphometric analyses on 27 common species of planktonic testate amoebae from genera Arcella, Centropyxis, Cucurbitella, Suiadifflugia, Difflugia, Lesquereusia and Netzelia. We sampled subsurface water from each lake in 72 lakes in four Brazilian floodplain lakes. Our goals were to assess: (1) the range of their morphological variability (a) over space within each floodplain, and (b) among the four floodplains, and (c) over time, and (2) which environmental factors explained this variation. Mean shell height and breadth varied considerably among the different floodplain lakes, especially in the Pantanal and Amazonian floodplains. The morphological variability of testate amoeba was correlated to environmental conditions (ammonia, nitrate, phosphate, chlorophyll-a, turbidity, temperature, and depth). Thus, understanding the morphological variation of the testate amoeba species can elucidate many questions involving the ecology of these organisms. Furthermore, could help molecular studies, bioindicator role of these organisations, environmental reconstruction, among others. PMID- 27682886 TI - Retinal Vessel Calibers in Predicting Long-Term Cardiovascular Outcomes: The Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events. METHODS: A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993-1995). RESULTS: During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08-1.18; HR, 1.18; 95% CI, 1.07-1.31; and HR, 1.10; 95% CI, 1.00-1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01-1.11; HR, 1.14; 95% CI, 1.03-1.26; and HR, 1.13; 95% CI, 1.03-1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction P=0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations-predicted 10-year atherosclerotic cardiovascular disease event risk <5% (overall risk, 3.9%), women in the narrowest arteriolar quartile had a 10-year event rate of 5.6% compared with 2.8% for women in the widest quartile (5.0% versus 3.4% for wider versus narrower venules). Retinal vessel caliber reclassified 21% of low-risk women (11% of all women) as intermediate risk (>5%). CONCLUSIONS: Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women. PMID- 27682891 TI - Diagnostic potential of extracellular RNA from biofluids. PMID- 27682892 TI - Implementation of Client Incentives within a Recovery Navigation Program. AB - OBJECTIVE: Multiple detoxification admissions among clients with substance use disorders (SUD) are costly to the health care system. This study explored the impact on behavior and cost outcomes of recovery support navigator (RSN) services delivered with and without a contingent incentive intervention. METHODS: New intakes at four detoxification programs were offered RSN-only (N=1116) or RSN plus incentive (RSN+I; N=1551) services. The study used a group-level cross-over design with the intervention in place at each clinic reversed halfway through the enrollment period. RSN+I clients could earn up to $240 in gift cards for accomplishing 12 different recovery-oriented target behaviors. All eligible clients entering the detoxification programs were included in the analyses, regardless of actual service use. RESULTS: Among RSN+I clients, 35.5% accessed any RSN services compared to 22.3% in the RSN-only group (p<.01). Of RSN+I clients, 19% earned one, 12% earned two and 18% earned three or more incentives; 51% did not earn any incentives. The majority of incentives earned were for meeting with the RSN either during or after detoxification. Adjusted average monthly health care costs among clients in the RSN-only and RSN+I groups increased at a similar rate over 12 months post-detoxification. DISCUSSION: Possible explanations for limited uptake of the incentive program discussed include features of the incentive program itself, navigator-client communication, organizational barriers and navigator bias. The findings provide lessons to consider for future design and implementation of multi-target contingency management interventions in real-world settings. PMID- 27682893 TI - Culturally Relevant Physical Activity through Elders in Motion: Physical Activity Programming for Older Aboriginal Adults in the Northwest Territories, Canada. AB - The 2011 National Household Survey found that the number of Aboriginal peoples in Canada aged 65 and over has increased by over 46 % since the 2006 Canadian Census (Statistics Canada 2011). Despite this dramatic increase in older Aboriginal peoples, there is a dearth of research concerning this cohort, especially regarding their engagement with physical activity. Using a case study methodology, this research sought to examine if the Northwest Territories (NWT) Recreation and Parks Association's (NWTRPA) Elders in Motion (EIM) program is culturally relevant for the participants. For this research we used a postcolonial theoretical framework since many of the participants in EIM are Aboriginal older adults and have experienced, and continue to experience, the effects of colonialism. To address this aim we conducted nine semi-structured interviews with EIM program leaders and NWTRPA staff, and supplemented these with archival research of EIM program documents. The findings show that the NWTRPA has adapted many EIM program documents for the participants and thus attempts to be culturally relevant for the participants. There are, however, aspects of the program that are not culturally relevant and actually reinforce colonialism, specifically with the program content (i.e. activities that are a part of EIM). In light of these findings, recommendations are offered for the NWTRPA on how the EIM program can become more culturally relevant for its Aboriginal participants. PMID- 27682894 TI - Interstitial lung disease in primary Sjogren's syndrome. AB - Interstitial lung disease (ILD) has been reported in 3 to 11% of patients with primary Sjogren's syndrome (pSS). The aims of this retrospective multicenter study were to: 1) analyze characteristics and outcome of ILD in pSS; and 2) evaluate predictive factors associated with ILD onset and deterioration. Twenty one of 263 patients with pSS (8%) developed ILD. ILD onset preceded pSS diagnosis (n=5), was concurrently identified in association with pSS (n=6) and developed after pSS onset (n=9). Presenting ILD manifestations were: acute/subacute (n=11) onset of ILD, symptomatic progressive onset of ILD (n=5), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT-scan (n=5). ILD therapy included: steroids (n=21), cyclophosphamide (n=1), azathioprine (n=4) and rituximab (n=1). The course of ILD was as follows: improvement (15.8%), stabilization (47.4%) or deterioration (36.8%). Predictive parameters of ILD onset were: older age (p=0.044), Raynaud's phenomenon (p=0.001) and esophageal involvement (p=0.001). Factors associated with ILD deterioration were: older age (p=0.038) and esophageal involvement (p=0.038). Thus, this study underscores the poor outcome of ILD during pSS; thus, systematic screening of pulmonary involvement is required in pSS patients, resulting in both diagnosis and management at early stage of ILD. We also suggest that patients presenting predictive factors of ILD deterioration may need a closer follow-up and a more aggressive therapy. PMID- 27682895 TI - Inducing bioactivity of dental ceramic/bioactive glass composites by Nd:YAG laser. AB - OBJECTIVES: Aims of this study were to investigate the optimal conditions of laser irradiation of a novel Bioactive Glass/Dental Ceramic-BP67 composite for acceleration of hydroxyapatite-HA formation and to assess cellular responses on the precipitated HA region. METHODS: BP67 (Bioactive Glass: 33.3%, Dental Ceramic: 66.7%) was fabricated by the sol-gel method. A laser assisted biomimetic LAB process was applied to BP67 sintered specimens immersed in 1.5-times concentrated simulated body fluid-1.5*-SBF. The effect of various energy densities of pulsed nanosecond Nd-YAG (1064nm) laser and irradiation exposure times (30min, 1 and 3h) were evaluated for HA precipitation. The HA film was characterized by FTIR, XRD, SEM and micro Raman techniques. ICP-AES was used for revealing changes in chemical composition of the 1.5*-SBF during irradiation. Cell viability and morphological characteristics of periodontal ligament fibroblasts-PDLFs, human gingival fibroblasts-HGFs and SAOS-2 osteoblasts on the HA surface were evaluated by MTT assays and SEM. RESULTS: At optimal energy fluence of 1.52J/cm2 and irradiation time for 3h followed by immersion in 1.5* SBF at 60 degrees C, a dense HA layer was formed on laser-irradiated BP67 within 7 days. The resulting HA film was tightly bonded to the underlying substrate and had mineral composition similar to cementum. MTT assay showed a consistent reduction of cell proliferation on the HA layer in comparison to conventional control ceramic and BP67 for all 3 cell lines studied. SIGNIFICANCE: These findings suggest LAB is an effective method for acceleration of HA formation on materials with low bioactivity, while cellular responses need further investigation. PMID- 27682896 TI - Measuring Users' Receptivity Toward an Integral Intervention Model Based on mHealth Solutions for Patients With Treatment-Resistant Schizophrenia (m-RESIST): A Qualitative Study. AB - BACKGROUND: Despite the theoretical potential of mHealth solutions in the treatment of patients with schizophrenia, there remains a lack of technological tools in clinical practice. OBJECTIVE: The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to a European integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m RESIST). METHODS: Before defining the system requirements, a qualitative study of the needs of outpatients with treatment-resistant schizophrenia was carried out in Spain, Israel, and Hungary. We analyzed the opinions of patients, informal carers, and clinicians concerning the services originally intended to be part of the solution. A total of 9 focus groups (72 people) and 35 individual interviews were carried out in the 3 countries, using discourse analysis as the framework. RESULTS: A webpage and an online forum were perceived as suitable to get both reliable information on the disease and support. Data transmission by a smart watch (monitoring), Web-based visits, and instant messages (clinical treatment) were valued as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions provided for improving the effectiveness of the solution. CONCLUSIONS: Positive receptivity toward m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact. PMID- 27682897 TI - Client Acceptability for Integrating Antiretroviral Therapy in Methadone Maintenance Therapy Clinics in Sichuan, China. AB - BACKGROUND: Using methadone maintenance therapy (MMT) clinics to deliver antiretroviral therapy (ART) has proven to be effective for promoting treatment initiation and adherence in drug users living with HIV. OBJECTIVES: The objective of this study was to investigate the HIV-positive client acceptability of integrated ART services and to identify the reasons for and factors associated with service acceptability. METHODS: A total of 86 HIV-positive MMT clients were recruited from 12 MMT clinics in Sichuan Province, China. They participated in a cross-sectional survey that queried their willingness to receive seven different types of MMT-based ART services. The reasons for their willingness/unwillingness to accept these services were documented. The association between service acceptability and background characteristics was examined. RESULTS: The most accepted integrated services were ART-related counseling (75.6%) and referral (73.2%). Concerns regarding the provider's lack of ART expertise and confidentiality issues were common barriers for the acceptance of MMT-based ART services. A trust relationship with MMT providers was a reason for service acceptance. Service acceptability was associated with a poorer perceived health status. Conclusions/Importance: ART-related services, based on the client perspective, can be delivered at MMT clinics. However, service provider training and the protection of confidentiality must be strengthened for the effective implementation of integrated service delivery. PMID- 27682898 TI - An Exact Solution for the Ground-level Gamma Dose Rate from a Spherical Gaussian Puff. AB - Analytical solutions of the absorbed dose rate integral for a spherically symmetric Gaussian puff were developed for both linear and Berger buildup approximations. Mathematically simpler solutions were also developed for the absorbed dose rate at the center of the puff. These solutions are valid for a ground-level receptor and both ground-level and elevated spherical puffs. Graphical solutions allow estimates of the ratio of the absorbed dose rate due to a puff to the absorbed dose rate for an infinite cloud with concentration equal to the maximum concentration at the center of the puff. Calculations also give the ratio of the absorbed dose rate integral due to photons from Compton scattering and secondary photons, assuming Berger buildup, to the absorbed dose rate integral using linear buildup for ranges of the Berger b parameter reported for air. PMID- 27682900 TI - Thoron Mitigation from Building Materials with Surface Barriers. AB - Thoron (Rn) exhalation from building materials has become increasingly recognized as a potential source for radiation exposure in dwellings. However, few studies have focused on mitigation strategies to reduce exposure from thoron and its progeny. Therefore, the purpose of this study is to (1) determine the reduction in thoron exhalation from building materials applied with regularly available surface barriers and (2) investigate the effects from surface roughness of the base material, barrier thickness, and surface cover on the thoron-retaining action of the surface barrier. The findings from this study demonstrate that regular surface barriers provide a potentially significant reduction in thoron exhalation, which can reach more than 90%. Despite this reduction, there are also materials that provide no reduction at all. Based on this work, no commonly available product property could be identified that provides good guidance on the barriers' performance to reduce thoron exhalation. PMID- 27682901 TI - Investigating Uranium Concentrations in Groundwaters in the State of Idaho Using Kinetic Phosphorescence Analysis and Inductively Coupled Plasma Mass Spectrometry. AB - The determination of uranium concentrations in natural water samples is of great interest due to the environmental consequences of this radionuclide. In this study, 380 groundwater samples from various locations within the state of Idaho were analyzed using two different techniques. The first method was Kinetic Phosphorescence Analysis (KPA), which gives the total uranium concentrations in water samples. The second analysis method was inductively coupled plasma mass spectrometry (ICP- MS). This method determines the total uranium concentration as well as the separate isotope concentrations of uranium. The U/U isotopic ratio was also measured for each sample to confirm that there was no depleted or enriched uranium present. The results were compared and mapped separately from each other. The study also found that in some areas of the state, natural uranium concentrations are relatively high. PMID- 27682899 TI - Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs. AB - The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to >=150 d) mitigated late effects in the lungs and kidneys after 12.5 Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 MUg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated. PMID- 27682902 TI - Modeling and Qualification of a Modified Emission Unit for Radioactive Air Emissions Stack Sampling Compliance. AB - A planned laboratory space and exhaust system modification to the Pacific Northwest National Laboratory Material Science and Technology Building indicated that a new evaluation of the mixing at the air sampling system location would be required for compliance to ANSI/HPS N13.1-2011. The modified exhaust system would add a third fan, thereby increasing the overall exhaust rate out the stack, thus voiding the previous mixing study. Prior to modifying the radioactive air emissions exhaust system, a three-dimensional computational fluid dynamics computer model was used to evaluate the mixing at the sampling system location. Modeling of the original three-fan system indicated that not all mixing criteria could be met. A second modeling effort was conducted with the addition of an air blender downstream of the confluence of the three fans, which then showed satisfactory mixing results. The final installation included an air blender, and the exhaust system underwent full-scale tests to verify velocity, cyclonic flow, gas, and particulate uniformity. The modeling results and those of the full-scale tests show agreement between each of the evaluated criteria. The use of a computational fluid dynamics code was an effective aid in the design process and allowed the sampling system to remain in its original location while still meeting the requirements for sampling at a well mixed location. PMID- 27682903 TI - Dynamic Radioactive Source for Evaluating and Demonstrating Time-dependent Performance of Continuous Air Monitors. AB - Evaluation of continuous air monitors in the presence of a plutonium aerosol is time intensive, expensive, and requires a specialized facility. The Radiation Protection Services Group at Los Alamos National Laboratory has designed a Dynamic Radioactive Source, intended to replace plutonium aerosol challenge testing. The Dynamic Radioactive Source is small enough to be inserted into the sampler filter chamber of a typical continuous air monitor. Time-dependent radioactivity is introduced from electroplated sources for real-time testing of a continuous air monitor where a mechanical wristwatch motor rotates a mask above an alpha-emitting electroplated disk source. The mask is attached to the watch's minute hand, and as it rotates, more of the underlying source is revealed. The measured alpha activity increases with time, simulating the arrival of airborne radioactive particulates at the air sampler inlet. The Dynamic Radioactive Source allows the temporal behavior of puff and chronic release conditions to be mimicked without the need for radioactive aerosols. The new system is configurable to different continuous air monitor designs and provides an in-house testing capability (benchtop compatible). It is a repeatable and reusable system and does not contaminate the tested air monitor. Test benefits include direct user control, realistic (plutonium) aerosol spectra, and iterative development of continuous air monitor alarm algorithms. Data obtained using the Dynamic Radioactive Source has been used to elucidate alarm algorithms and to compare the response time of two commercial continuous air monitors. PMID- 27682905 TI - Analysis of Natural and Anthropogenic Radionuclide Content in Palm Date Fruit of the United Arab Emirates: A Baseline Study. AB - The purpose of this study is to contribute to a wider effort of establishing an environmental radiation baseline for the United Arab Emirates (UAE) before the startup of the country's first nuclear reactor in 2017. An investigation of gamma emitting radionuclide concentrations in palm dates grown in the UAE was performed. Palm date samples of 10 varieties originating from several local commercial date palm farms of the UAE were collected and analyzed. The study targeted the naturally occurring radionuclides, such as U, Th, and K, in addition to any potential anthropogenic radionuclides, such as Cs and others. Gamma spectrometry revealed measured activity concentrations for U (Ra), Th (Ra), and K that ranged from 0.61 to 0.80 Bq kg, 0.10 to 0.23 Bq kg, and 191 to 362 Bq kg, respectively, on a dry-weight basis, and calculated activity concentrations on a wet basis ranged from 0.52 to 0.69 Bq kg, 0.09 to 0.22 Bq kg, and 168 to 297 Bq kg, respectively. No Cs or other anthropogenic radionuclides could be detected in this study. All measurements were performed using a coaxial HPGe detector with 40% relative efficiency quoted by the manufacturer. Efficiency calibration correction factors were calculated using Angle software. PMID- 27682904 TI - Early Intake of Radiocesium by Residents Living Near the TEPCO Fukushima Dai-Ichi Nuclear Power Plant after the Accident. Part 1: Internal Doses Based on Whole body Measurements by NIRS. AB - The Tokyo Electric Power Company's Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident in 2011 resulted in a release of radionuclides into the environment (I: 142.9 PBq, Cs:12.4 PBq). This study presents the results of internal doses to 174 residents living near the FDNPP at the time of the accident based on whole-body (WB) measurements performed by the National Institute of Radiological Sciences (NIRS) during the period between 27 June and 28 July 2011. The 174 subjects consisted of 125 adults (>=18-y) and 49 children (<18-y) and included 90 persons of Namie town, one of the municipalities heavily contaminated with the radionuclides. The number of subjects with significant detection of both Cs and Cs was relatively small: 28.8% for the adults and 4.1% for the children. A significant gender difference in the Cs detection rate (males > females) was observed in the adults but not the children. In this study, the committed effective dose (CED) from Cs and Cs was calculated based on individual WB contents (Cs) corrected against body size, the observed body content ratio of Cs to Cs, and the assumed intake scenario (namely, acute inhalation of Type F compounds on 12 March 2011 when the first explosive event occurred at the site of the FDNPP). The 90th-percentile CED value for the adults was around 0.1 mSv and the maximum CED (0.63 mSv) was found in an elderly male. Comparable CED results were obtained in other WB measurements subsequently performed by the Japan Atomic Energy Agency (JAEA) in a similar manner to that of the NIRS, suggesting that the contribution of ingestion to the WB content observed would be trivial for most of the JAEA subjects. The intake ratio of I to Cs was evaluated to be 3~5 based on the I thyroid measurement data of Tokonami et al. Using the average intake ratio of 3.8, the resulting median and maximum thyroid-equivalent doses to the adult subjects of this study were estimated at 3.5 mSv and 84 mSv, respectively. PMID- 27682906 TI - The Current Limits for Radionuclides in Food in Japan. AB - After the TEPCO Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, the current limits in Japan on the radionuclide contamination of food [100 Bq kg for general foods, 50 Bq kg for milk and infant foods, and 10 Bq kg for drinking water as radioactive cesium (Cs + Cs)] were established on the basis of an effective dose of 1 mSv y, consistent with international standards to mitigate the exposure of the general public to radiation. Measures that include recalling or restriction of food have been taken in cases when these limits were violated. As a result of these efforts, the actual effective doses of radioactive cesium (Cs + Cs) in foods approximately 1 y after the FDNPP accident were below 0.01 mSv y. However, there is little information on the current status of these limits in the literature, which necessitates a comprehensive review of the information that exists. In this paper, the concept behind the introduction of these limits, the methods by which they were derived, and the results of monitoring food accordingly, are reviewed. This information will be helpful in the case of a future accident, and it will also help to enhance the understanding of the current limits and to relieve the anxieties of the general public concerning radiation exposure from radionuclides in food. PMID- 27682911 TI - Qualified staff kept on low grades, says RCN. AB - Enrolled nurses who have successfully completed conversion courses are still being employed at grade C, according to RCN General Secretary Christine Hancock. PMID- 27682910 TI - Is money where his mouth is? AB - Prime Minister John Major paid nursing something of a compliment last week. With speculation about the date of the next General Election at fever pitch, he chose this year's Nursing Standard/BUP A Nursing Nurse 91 awards ceremony to make a major speech about health care in general and the profession in particular. PMID- 27682912 TI - Unions demand above-inflation rises. AB - Nursing unions have demanded an above-inflation pay rise and an end to phased increases in the next pay award. The Review Body has also been asked to move 'towards a fair rate of nursing pay' and ensure its recommendations cover staff in self-governing Trusts. PMID- 27682913 TI - Major promises 'named nurse' under Charter. AB - Every patient can expect a named nurse or midwife who will be responsible for their care 'from start to finish' under the forthcoming Patients' Charter, Prime Minister John Major pledged when he presented the Nursing Standard/BUPA Nursing Nurse 91 awards last week. PMID- 27682914 TI - Pink is sacked but speaks up for the whistleblowers. AB - Nursing can only move forward if the profession is prepared to speak out against poor standards, whistleblowing charge nurse Graham Pink warned last week after he was sacked by Stockport Health Authority for alleged gross misconduct. PMID- 27682915 TI - Ashworth inquiry. AB - Student nurse placements have been suspended at Ashworth Hospital in Merseyside until the public inquiry into allegations of patient abuse has ended. PMID- 27682916 TI - ? AB - Arthritis force: Celebrities who suffer from arthritis, including Dave Prowse, Darth Vader in Star Wars, joined children from the Bath Institute of Rheumatic Diseases to launch the Force Against Arthritis campaign in London. PMID- 27682917 TI - Health unions attack 'hire and fire' report. AB - Health unions have condemned a Department of Health commissioned report suggesting opted-out hospitals should get rid of permanent staff and take on contract workers to save money. PMID- 27682919 TI - Nursing Update pilot to be screened this week. AB - RCN Nursing Update - a system of continuing education broadcasting for Britain's 600,000 nurses - will take to the air in a special pilot edition on Friday. PMID- 27682918 TI - Mental health. AB - Nurses at the Royal Edinburgh Hospitalhave been told either to stop making 'destructive' comments about mental health services in Lothian or resign. PMID- 27682920 TI - Major organisations seek top discussions. AB - A coalition of major organisations involved in providing services for people with learning disabilities is seeking a meeting with Health Minister Stephen Dorrell to discuss issues arising from the Minister's policy statement on the development of better services. PMID- 27682921 TI - ? AB - A new guide on how the Children Act will affect NHS staff was launched by Health Minister Virginia Bottomley. PMID- 27682922 TI - Nursing audit. AB - Margaret Macdonald is to head the new Scottish Nursing Audit Development Project. The appointment was announced by Scottish Chief Nurse Yvonne Moores at a conference to launch the final report of the Scottish Nursing Standards Project, which Ms Macdonald has coordinated. She will lead a team of five nurses who will promote a practitioner- based approach to nursing audit. PMID- 27682923 TI - Dissatisfaction with redundancy measures. AB - Older nurses at two Shropshire hospitals which are about to close are angry at not being offered redundancy as younger nurses were. Sixty nurses at Shifnal and Beeches hospitals had applied for redundancy but only 28 were accepted. PMID- 27682924 TI - Government' foils to take ENs seriously'. AB - Statutory bodies are not representing the interests of enrolled nurses and must now be freed from Government interference, a COHSE, conference heard last week. PMID- 27682925 TI - ? AB - Values in Action, the national campaign group for people with learning disabilities, held gatherings at the gates of hospitals throughout the country last week, calling for the closure of mental handicap hospitals and demanding extra funding for community care. PMID- 27682928 TI - Care strategy helps sufferers. AB - Poor attention, little continuity in treatment and a lack of understanding has meant that sickle cell suffers endure more pain than they should, specialist nurses told a national sickle cell conference in Cardiff last week. PMID- 27682926 TI - Equal opportunities. AB - Four unions representing hospital ancillary staff have made a claim for better treatment of 102,000 women parttimers. NUPE, COHSE, GMB and TGWU are asking for time and a half pay for working Saturdays, paid bank holidays and paid overtime rates for working extra hours. Malcolm Wing, NUPE national secretary, said: 'Our claim is to win equality for women part-timers.' PMID- 27682927 TI - Nurses mistrust plans to cut night casualty. AB - Nurses have accused Leicestershire Health Authority of using inadequate staff security as an excuse for the planned night time closure of casualty units. PMID- 27682930 TI - Call for more community nurse services. AB - Children stay in hospital for longer than is necessary or are cared for by their parents at home without adequate support because of the shortage of paediatric community nursing services around the country, according to the Chief Nursing Officer for Wales. PMID- 27682929 TI - Nursing parents need 'teaching and support '. AB - Parents were able to take on the nursing care of their children in hospital for a wide range of conditions, provided they were carefully taught and supported, nurses in a Welsh scheme found. PMID- 27682931 TI - Asthma. AB - Childhood mortality rates from asthma are remaining constant, with about 40 deaths in the UK each year, despite the increasingly wide range of drugs available, delegates heard. PMID- 27682933 TI - Nurses retrained to stop spread of HIV. AB - Romanian nurses are being retrained in the proper use of needles, syringes and sterilisation techniques after researchers warned that current practices might be spreading HIV. PMID- 27682935 TI - Home visits best for adolescent asthmatics. AB - The best way to ensure that young people comply with asthma treatment is to see them in their own homes, school nurse Dorothy Orrell told a London meeting on teenagers and asthma last week. PMID- 27682934 TI - Doctors admit lethal doses administered. AB - Doctors admitted they had administered lethal drug doses at patients' requests in 1.8 per cent of deaths studied in a survey in the Netherlands. PMID- 27682937 TI - World news. AB - Austria Computer tomography is being used to measure the density of kidney stones in patients attending the urological clinic at Innsbruck Medical School. PMID- 27682938 TI - ? AB - World AIDS Day The World Health Organization has warned against widespread complacency, denial or cutbacks in AIDS funding in the light of new evidence showing progress in halting the spread of the pandemic. PMID- 27682939 TI - HIV-positive patients claim discrimination. AB - Refusal of a requested health service is a particularly common form of discrimination against people who are HIV positive, Italian researchers say. Anonymous questionnaires were completed by 86 in- and out-patients at one AIDS unit, of whom 63 were intravenous drug users, 11 heterosexual, nine homosexual and three had no known risk factors, Eighty- four were HIV-positive and the other two were at high risk of infection. PMID- 27682940 TI - Anticancer drug gets cells back in line. AB - American researchers have developed a new anticancer drug that 're-educates' cells instead of killing them. The drug, yet to be named, was developed from another compound, HMBA. The drawbacks of HMBA are the large doses required and the side-effects. PMID- 27682941 TI - Short-term success for otitis media antibiotics. AB - Antibiotics substantially improve the short-term outcome in children with mild otitis media, but do not seem to influence medium or long-term results. PMID- 27682942 TI - Pregnancy follows endometrial resection. AB - A tubal occlusive procedure prior to transcervical endometrial resection (TCER) might be prudent, researchers from Bournemouth say. PMID- 27682943 TI - 'Cold sores' and safer sex. AB - Safer sex campaigns should cover all aspects of herpes simplex virus (HSV) infectiousness, researchers say. PMID- 27682944 TI - Time for a fair deal. AB - Staff representatives revealed this week the evidence to be submitted to the Review Body for Nursing Staff, Midwives and Health Visitors in the run-up to the 1992 pay award, with demands for an immediate move 'towards a fair rate of nursing pay'. PMID- 27682945 TI - A project comes alive. AB - RCN Nursing Update, a unique project in continuing education for nurses, midwives and health visitors goes on air this week. The first pilot of this exciting venture is broadcast on BBC 1 at 1.1 5am on Friday September 27. This week's issue of Nursing Standard includes a special supplement to complement the programme. PMID- 27682946 TI - Assessment. AB - Assessment will be in two stages; the first stage is the assessment of knowledge about the subject of the unit of learning. Entry to assessment will be by application to the IANE, using an application form in the Nursing Standard supplement accompanied by the fee. PMID- 27682947 TI - Planning. AB - The educational responsibility for RCN Nursing Update rests with the Institute of Advanced Nursing Education (IANE). PMID- 27682948 TI - Take care when counselling. AB - I read Points of View (Nursing StandardAugust 14) with considerable concern and would like to challenge Barbara Eunson on three points: holistic nursing, other professionals' qualifications and counselling/psychotherapy. PMID- 27682949 TI - HIV patients should be equal. AB - I agree with landmark Director Jonathan Grimshaw's assertion that health professionals who refuse to treat patients with HIV ('Declaration attacks HIV discrimination', Nursing Standard News, September 4) should be sanctioned. PMID- 27682950 TI - Thank you and goodnight. AB - I agree with D D MacGregor's letter 'Out of fashion but fitting' (Nursing Standard August 14), expressing concern over unsuitable nightwear for hospital patients. PMID- 27682951 TI - Casualty update. AB - It was Jimmy's turn to cock it up (again), getting it wrong about whether or not to remove a burns casualty's clothing. PMID- 27682952 TI - Correction. AB - In Temperature taking - getting it right' (Nursing Standard December 12 1990), the author erroneously referred to TcmpaDOT thermometers as using liquid crystal indicators. They in fact function through a colour change, using a mix of two organic chemicals. PMID- 27682953 TI - Never too late to refresh. AB - It is upsetting that C Love's mother felt 'let down' at being offered a four month intensive course (Nursing Standard Letters, September 4). Surely, her spell back in nursing and her refresher course made her aware of the many ongoing changes in nursing and the benefits of further courses? PMID- 27682954 TI - Val Kavanagh. AB - Val Kavanagh, who worked as an enrolled nurse at Trevalyn Hospital, Rossett, Clwyd, died on August 9 1991. PMID- 27682955 TI - Information exchange. AB - I am a sister running a pre-admission assessment clinic, and am planning to write a dissertation on either a cost-benefit analysis of such a clinic or a comparative study with other such clinics that are hospital or community- based, run by doctors, nurses or a multidisciplinary team. PMID- 27682957 TI - Management comes clean. AB - The name's Health ... Nat Health, Special Investigator into Services that Care. PMID- 27682956 TI - Points of View. AB - 'Nurses required for World Student Games', the advertisement read. PMID- 27682958 TI - Nursing Care of the Burn-Injured Patient R B Trofino F A Davis Nursing Care of the Burn-Injured Patient 466pp L33-50 0-8036-8658-7 [Formula: see text]. AB - The foreword states 'a nursing text which emphasises nursing process and focuses on all aspects of burn care from emergency treatment through rehabilitation and all age groups should make a significant contribution to the care of these complex patients.' Nursing Care of the Burn-Injured Patient does precisely that. With a US audience in mind, it may not make quite the 'significant contribution' it should in the UK. PMID- 27682960 TI - Nursing A Perry and M Jolley Nursing editors Edward Arnold 352pp L13.95 0-340 51492-2 [Formula: see text]. AB - Nursing: A Knowledge Base for Practice, for pre- and post-registration levels, is a major contribution towards assisting such students to understand and appreciate the theoretical framework that supports the art and science of nursing. PMID- 27682961 TI - HIV roundup. AB - World AIDS Day The National AIDS Trust is co-ordinating UK activities for World AIDS Day on December 1. A newsletter, funded by the Health Education Authority, will be published monthly for four issues to inform everyone involved in planning, organising or running an event. PMID- 27682962 TI - Listings. PMID- 27682963 TI - Explaining socioeconomic inequalities in self-rated health: a systematic review of the relative contribution of material, psychosocial and behavioural factors. AB - BACKGROUND: Material, psychosocial and behavioural factors are important explanatory pathways for socioeconomic inequalities in health. The aim of this systematic review was to summarise the available evidence on empirical studies and to analyse the relative contribution of these factors for explaining inequalities in self-rated health. METHODS: The study was performed in compliance with PRISMA guidelines. The literature search was conducted in the electronic databases PubMed and Web of Science (1996-2016) as well as by screening of reference lists of obtained articles. Two reviewers performed the search and critical appraisal of the studies. All studies that focus on explaining socioeconomic inequalities in self-rated health, including at least 2 of the 3 main pathways and analysing the relative contribution of these approaches in separate and joint models, were included. RESULTS: Eleven publications were included. Separate analyses showed that material, psychosocial and behavioural factors contribute to the explanation of socioeconomic inequalities in self-rated health. However, the combined analyses revealed that material factors contributed most to differences in self-rated health because of their higher independent (direct) effect and additional shared (indirect) effect (through psychosocial and behavioural factors). These results were largely independent of age, gender and indicator of socioeconomic status. CONCLUSIONS: The evidence presented might be used for policymakers to identify and to justify prioritisation in terms of prevention and health promotion. The findings show that multiple factors are important for tackling social inequalities in health. Strategies for reducing these inequalities should focus on material/structural living conditions as they shape conditions of psychosocial resources and health behaviour. PMID- 27682964 TI - Stability study of sodium colistimethate-loaded lipid nanoparticles. AB - In the last decades, the encapsulation of antibiotics into nanoparticulate carriers has gained increasing attention for the treatment of infectious diseases. Sodium colistimethate-loaded solid lipid nanoparticles (Colist-SLNs) and nanostructured lipid carriers (Colist-NLCs) were designed aiming to treat the pulmonary infection associated to cystic fibrosis patients. The nanoparticles were freeze-dried using trehalose as cryoprotectant. The stability of both nanoparticles was analysed over one year according to the International Conference of Harmonisation (ICH) guidelines by determining the minimum inhibitory concentration (MIC) against clinically isolated Pseudomonas aeruginosa strains and by studying their physico-chemical characteristics. The results showed that Colist-SLNs lost their antimicrobial activity at the third month; on the contrary, the antibacterial activity of Colist-NLCs was maintained throughout the study within an adequate range (MIC <=16 MUg/mL). In addition, Colist-NLCs exhibited suitable physico-chemical properties at 5 degrees C and 25 degrees C/60% relative humidity over one year. Altogether, Colist-NLCs proved to have better stability than Colist-SLNs. PMID- 27682965 TI - Provider experiences with the large-scale 'Helping Babies Breathe' training programme in Tanzania. AB - OBJECTIVES: Worldwide, there has been renewed emphasis on reducing neonatal mortality in low-resource countries. The Helping Babies Breathe (HBB) programme has been shown to reduce newborn deaths. The aim of this study is to present provider-level perceptions and experiences of the HBB programme implemented at scale in Tanzania and identify key lessons learned for scalability in similar and other settings. METHODS: Focus group discussions with HBB-trained providers were conducted using a prospective longitudinal study design between October 2013 and May 2015. A semi-structured discussion guide was used to facilitate the focus groups which were held 4-6 weeks and 4-6 months post-HBB training. Data were managed using NVivo software and analysed thematically. RESULTS: A total of 222 focus group discussions were conducted in 252 trained facilities and involved 599 providers across 15 regions of Tanzania. Birth attendants reported that the training programme helped increase knowledge, skills and confidence, and that the provided equipment simplified resuscitation. Supportive supervision and regular follow-up visits were considered critical for skills retention. On the other hand, the brief 1-day training in Tanzania, small financal incentives, intra facility rotations of trained attendants, staff shortages, limited rescucitation spaces and mastery of the bag-and-mask were considered challenges to the HBB programme in Tanzania. DISCUSSION: The HBB programme was largely very well received during its first at-scale implementation in Tanzania. Addressing the main challenges cited by participants, particularly the training duration, may increase provider satisfaction with the HBB training programme. PMID- 27682966 TI - Human papillomavirus infection and cervical lesions in rheumatic diseases: a systematic review. AB - An association between immune-mediated diseases and cervical pre-malignant and malignant lesions is described, having the human papillomavirus (HPV) infection a causal role. Related studies have been generally focused on systemic lupus erythematosus (SLE) patients, but relatively to other diseases, such as rheumatoid arthritis (RA), Sjogren's syndrome (SS) and systemic sclerosis (SSc), data has not been systematically evaluated. We conducted a systematic review analysis of the literature in PubMed, including articles published until March of 2015, in patients with RA, SS, SLE and SSc, to evaluate the frequency of HPV infection, cervical dysplasia and cervical cancer, and associated factors, with particular interest on the role of glucocorticoids and immunosuppressive treatment. Moreover, safety and efficacy of HPV vaccines in these patients was investigated. Of 476 articles identified, 27 were finally included. The studies showed an increased prevalence of cervical dysplasia and cancer, with the HPV infection being an important associated factor, in particular in SLE patients. The data relatively to other rheumatic diseases was very scarse, but an increased prevalence of smear abnormalities was also found in RA. Patients exposed to glucocorticoids and to long-term immunosuppression, particularly cyclophosphamide, have increased risk of presenting more pre-malignant lesions than the general population. The available vaccines seem to be generally safe and immunogenic in the short- period evaluation, but long-term follow-up is required to evaluate the impact of the vaccine in the protection against HPV infection and occurrence of high-grade cervical lesions. PMID- 27682967 TI - Idiopathic nephrotic syndrome: the EBV hypothesis. AB - Steroid sensitive nephrotic syndrome is marked by a massive proteinuria and loss of podocytes foot processes. The mechanism of the disease remains debated but recent publications suggest a primary role of Epstein-Barr Virus (EBV). EBV replication in the peripheral blood is found in 50% of patients during the first flare of the disease. The genetic locus of steroid sensitive nephrotic syndrome was also identified as influencing antibodies directed against EBNA1. EBV is able to establish, latent benign infection in memory B cells that display phenotypes similar to antigen-selected memory B cells. Consistently, memory B cells reconstitution after rituximab infusion is a predictor of the relapse of proteinuria. We suggest that a specific anti-EBNA1 antibody internalized in the podocytes via the neonatal Fc receptor might cross-react with a major protein present in the same cell trafficking compartment. The diversion of this major podocyte protein in the urinary space and the subsequent depletion is supposed to result in podocyte damages with loss of foot processes and massive proteinuria. Immunosuppression of B cells and subsequent clearance of anti-EBNA1 antibodies would lead to a restoration of the normal level of the protein allowing recovery of proteinuria and of normal podocyte morphology. PMID- 27682969 TI - Bronchopulmonary dysplasia: new becomes old again! AB - Despite the many advances in neonatology, bronchopulmonary dysplasia (BPD) continues to be a frustrating disease of prematurity. BPD is a disease which is defined oddly by its treatment rather than its pathophysiology, leading to frequently changing nomenclature which has widespread implications on our ability to both understand and follow the progression of BPD. As various treatment modalities for BPD were developed and a larger number of extremely preterm infants survived, the "old" BPD based on lung injury from oxygen therapy and mechanical ventilation transitioned into a "new" BPD focused more on the interruption of normal development. However, the interruption of normal development does not solely apply to lung development. The effects of prematurity on vascular development cannot be overstated and pulmonary vascular disease has become the new frontier of BPD. As we begin to better understand the complex, multifactorial pathophysiology of BPD, it is necessary to again focus on appropriate, pathology-driven nomenclature that can effectively describe the multiple clinical phenotypes of BPD. PMID- 27682970 TI - Capillary electrophoresis/immunosubtraction as a better alternative to immunofixation for detecting and immunotyping serum monoclonal proteins in patients with immunoglobulin light chain (AL) amyloidosis. AB - Capillary electrophoresis/immunosubtraction (CE/IS) is a simple method for detecting and immunotyping serum or urine monoclonal proteins. To our knowledge, there are no previous reports of the use of CE/IS for characterizing patients with Immunoglobulin light chain (AL) amyloidosis, and there are no convincing data available to compare CE/IS with serum immunofixation electrophoresis (IFE) and free light chain (FLC) assay. The aim of this study was to evaluate the clinical utility of CE/IS in patients with AL amyloidosis as a diagnostic accuracy study. This study included 50 patients with AL amyloidosis (17 newly diagnosed and 33 undergoing treatment). Serum IFE identified monoclonal proteins in 15/50 (30%) of all cases and in 7/17 (41%) of newly diagnosed cases. CE/IS identified monoclonal proteins in 16/50 (32%) of all cases and in 7/17 (41%) of newly diagnosed cases. The FLC assay detected an abnormal ratio of kappa and lambda light chains in 26/50 (52%) of all cases and in 15/17 (88%) of newly diagnosed cases. IFE and CE/IS combined with FLC assay identified monoclonal proteins more sensitive than IFE alone and CE/IS alone, in newly diagnosed patients (p = 0.002 and 0.002, respectively) and in patients undergoing treatment (p = 0.031 and 0.016, respectively). CE/IS is an acceptable alternative to IFE. PMID- 27682974 TI - Measuring the Complex Optical Conductivity of Graphene by Fabry-Perot Reflectance Spectroscopy. AB - We have experimentally studied the dispersion of optical conductivity in few layer graphene through reflection spectroscopy at visible wavelengths. A laser scanning microscope (LSM) with a supercontinuum laser source measured the frequency dependence of the reflectance of exfoliated graphene flakes, including monolayer, bilayer and trilayer graphene, loaded on a Si/SiO2 Fabry-Perot resonator in the 545-700 nm range. The complex refractive index of few-layer graphene, n - ik, was extracted from the reflectance contrast to the bare substrate. It was found that each few-layer graphene possesses a unique dispersionless optical index. This feature indicates that the optical conductivity does not simply scale with the number of layers, and that inter layer electrodynamics are significant at visible energies. PMID- 27682975 TI - A persistent cough. PMID- 27682976 TI - One or two? PMID- 27682977 TI - Developments in the field of allergy mechanisms in 2015 through the eyes of Clinical & Experimental Allergy. AB - In the first of two papers we described the development in the field of allergy mechanisms as described by Clinical and Experimental Allergy in 2015. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered. A second paper will cover clinical aspects. PMID- 27682968 TI - Hirschsprung's disease: clinical dysmorphology, genes, micro-RNAs, and future perspectives. AB - On the occasion of the 100th anniversary of Dr. Harald Hirschsprung's death, there is a worldwide significant research effort toward identifying and understanding the role of genes and biochemical pathways involved in the pathogenesis as well as the use of new therapies for the disease harboring his name (Hirschsprung disease, HSCR). HSCR (aganglionic megacolon) is a frequent diagnostic and clinical challenge in perinatology and pediatric surgery, and a major cause of neonatal intestinal obstruction. HSCR is characterized by the absence of ganglia of the enteric nervous system, mostly in the distal gastrointestinal tract. This review focuses on current understanding of genes and pathways associated with HSCR and summarizes recent knowledge related to micro RNAs (miRNAs) and HSCR pathogenesis. While commonly sporadic, Mendelian patterns of inheritance have been described in syndromic cases with HSCR. Although only half of the patients with HSCR have mutations in specific genes related to early embryonic development, recent pathway-based analysis suggests that gene modules with common functions may be associated with HSCR in different populations. This comprehensive profile of functional gene modules may serve as a useful resource for future developmental, biochemical, and genetic studies providing insights into the complex nature of HSCR. PMID- 27682979 TI - Parents' confidence in recommended childhood vaccinations: Extending the assessment, expanding the context. AB - There has been significant and growing interest in vaccine hesitancy and confidence in the United States as well as across the globe. While studies have used confidence measures, few studies have provided in-depth assessments and no studies have assessed parents' confidence in vaccines in relationship to other frequently recommended health-related products for young children. This study used a nationally representative sample of 1000 US parents to identify confidence levels for recommended vaccinations, antibiotics, over-the-counter (OTC) medicines, and vitamins for children. The analyses examined associations between confidence ratings, vaccination behaviors and intentions, and trust in healthcare provider, along with associations between confidence ratings and use of the other health-related products. Parents' confidence in vaccines was relatively high and high relative to antibiotics, OTC medicines and vitamins. For all 4 health related products examined, past product experience and knowledge of bad or adverse outcomes negatively impacted parents' confidence levels. Confidence levels were associated with both trust in advice from their child's healthcare provider and acceptance of healthcare provider recommendations. Parents in some groups, such as those with lower income and education levels, were more likely to have less confidence not just in vaccines, but also in antibiotics and OTC medicines for children. Overall, the findings extend understanding of vaccine confidence, including by placing it into a broader context. PMID- 27682980 TI - Regulation of PCGEM1 by p54/nrb in prostate cancer. AB - PCGEM1 is a long non-coding RNA (lncRNA) that is often upregulated in prostate cancer. However, little is known how PCGEM1 is regulated. In the present study, we show transcriptional regulation of PCGEM1 in response to androgen deprivation by p54/nrb. While ectopic expression of p54/nrb increases, suppression of p54/nrb by RNAi or knockout (KO) reduces PCGEM1. Moreover, rescue experiments indicate that re-expression of p54/nrb in KO cells restores the ability to induce PCGEM1, leading to upregulation of the androgen receptor splice variant AR3 which has been shown to play a role in castration resistance. Finally, 3,3' Diindolylmethane (DIM), a known chemoprevention agent, is capable of suppressing PCGEM1 expression by preventing the interaction of p54/nrb with the PCGEM1 promoter. In particular, DIM reduces tumor growth by suppression of PCGEM1 and promoting apoptosis in the castrated xenograft mouse model. Together, these results demonstrate a novel mechanism of p54/nrb-mediated expression of PCGEM1 and AR3, contributing to castration resistance in prostate cancer. PMID- 27682983 TI - Consensus or Deadlock? Consequences of Simple Behavioral Rules for Coordination in Group Decisions. AB - Coordinated collective behaviors often emerge from simple rules governing the interactions of individuals in groups. We model mechanisms of coordination among ants during cooperative transport, a challenging task that requires a consensus on travel direction. Our goal is to determine whether groups following simple behavioral rules can reach a consensus using minimal information. Using deterministic and stochastic models, we investigate behavioral factors that affect coordination. We define and investigate three types of behavioral rules governing individual behavior that differ in the information available: individuals either 1) have no information, 2) can measure transport success, or 3) measure success while also knowing whether they are aligned with the majority. We find that groups break deadlocks only if individuals more readily give up when they are going against the majority, corresponding to rule type 3 -such groups are "informed." These behavioral rules succeed through positive and negative feedbacks that are implemented in our model via a single mechanism: individuals only need to measure the relative group sizes to make effective decisions. We also find that groups reach consensus more quickly if they have either a shared bias, high sensitivity to group behavior, or finely tuned persistence. Each of these is a potential adaptation for efficient cooperative transport. This flexibility makes the behavioral rules in the informed case relatively robust to deficiencies in the individuals' capabilities. While inspired by ants, our results are generalizable to other collective decisions with deadlocks, and demonstrate that groups of behaviorally simple individuals with no memory and extremely limited information can break symmetry and reach a consensus in a decision between two equal options. PMID- 27682981 TI - Identification of a Novel Human E-Cadherin Splice Variant and Assessment of Its Effects Upon EMT-Related Events. AB - Epithelial Cadherin (E-cadherin) is involved in calcium-dependent cell-cell adhesion and signal transduction. The E-cadherin decrease/loss is a hallmark of Epithelial to Mesenchymal Transition (EMT), a key event in tumor progression. The underlying molecular mechanisms that trigger E-cadherin loss and consequent EMT have not been completely elucidated. This study reports the identification of a novel human E-cadherin variant mRNA produced by alternative splicing. A bioinformatics evaluation of the novel mRNA sequence and biochemical verifications suggest its regulation by Nonsense-Mediated mRNA Decay (NMD). The novel E-cadherin variant was detected in 29/42 (69%) human tumor cell lines, expressed at variable levels (E-cadherin variant expression relative to the wild type mRNA = 0.05-11.6%). Stable transfection of the novel E-cadherin variant in MCF-7 cells (MCF7Ecadvar) resulted in downregulation of wild type E-cadherin expression (transcript/protein) and EMT-related changes, among them acquisition of a fibroblastic-like cell phenotype, increased expression of Twist, Snail, Zeb1, and Slug transcriptional repressors and decreased expression of ESRP1 and ESRP2 RNA binding proteins. Moreover, loss of cytokeratins and gain of vimentin, N-cadherin and Dysadherin/FXYD5 proteins was observed. Dramatic changes in cell behavior were found in MCF7Ecadvar, as judged by the decreased cell-cell adhesion (Hanging-drop assay), increased cell motility (Wound Healing) and increased cell migration (Transwell) and invasion (Transwell w/Matrigel). Some changes were found in MCF-7 cells incubated with culture medium supplemented with conditioned medium from HEK-293 cells transfected with the E-cadherin variant mRNA. Further characterization of the novel E-cadherin variant will help understanding the molecular basis of tumor progression and improve cancer diagnosis. J. Cell. Physiol. 232: 1368-1386, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27682982 TI - Molecular mechanisms of Slo2 K+ channel closure. AB - KEY POINTS: Intracellular Na+ -activated Slo2 potassium channels are in a closed state under normal physiological conditions, although their mechanisms of ion permeation gating are not well understood. A cryo-electron microscopy structure of Slo2.2 suggests that the ion permeation pathway of these channels is closed by a single constriction of the inner pore formed by the criss-crossing of the cytoplasmic ends of the S6 segments (the S6 bundle crossing) at a conserved Met residue. Functional characterization of mutant Slo2 channels suggests that hydrophobic interactions between Leu residues in the upper region of the S6 segments contribute to stabilizing the inner pore in a non-conducting state. Mutation of the conserved Met residues in the S6 segments to the negatively charged Glu did not induce constitutive opening of Slo2.1 or Slo2.2, suggesting that ion permeation of Slo2 channels is not predominantly gated by the S6 bundle crossing. ABSTRACT: Large conductance K+ -selective Slo2 channels are in a closed state unless activated by elevated [Na+ ]i . Our previous studies suggested that the pore helix/selectivity filter serves as the activation gate in Slo2 channels. In the present study, we evaluated two other potential mechanisms for stabilization of Slo2 channels in a closed state: (1) dewetting and collapse of the inner pore (hydrophobic gating) and (2) constriction of the inner pore by tight criss-crossing of the cytoplasmic ends of the S6 alpha-helical segments. Slo2 channels contain two conserved Leu residues in each of the four S6 segments that line the inner pore region nearest the bottom of the selectivity filter. To evaluate the potential role of these residues in hydrophobic gating, Leu267 and Leu270 in human Slo2.1 were each replaced by 15 different residues. The relative conductance of mutant channels was highly dependent on hydrophilicity and volume of the amino acid substituted for Leu267 and was maximal with L267H. Consistent with their combined role in hydrophobic gating, replacement of both Leu residues with the isosteric but polar residue Asn (L267N/L270N) stabilized channels in a fully open state. In a recent cryo-electron microscopy structure of chicken Slo2.2, the ion permeation pathway of the channel is closed by a constriction of the inner pore formed by criss-crossing of the S6 segments at a conserved Met. Inconsistent with the S6 segment crossing forming the activation gate, replacement of the homologous Met residues in human Slo2.1 or Slo2.2 with the negatively-charged Glu did not induce constitutive channel opening. PMID- 27682985 TI - Portable electronic vision enhancement systems in comparison with optical magnifiers for near vision activities: an economic evaluation alongside a randomized crossover trial. AB - PURPOSE: To determine the incremental cost-effectiveness of portable electronic vision enhancement system (p-EVES) devices compared with optical low vision aids (LVAs), for improving near vision visual function, quality of life and well-being of people with a visual impairment. METHODS: An AB/BA randomized crossover trial design was used. Eighty-two participants completed the study. Participants were current users of optical LVAs who had not tried a p-EVES device before and had a stable visual impairment. The trial intervention was the addition of a p-EVES device to the participant's existing optical LVA(s) for 2 months, and the control intervention was optical LVA use only, for 2 months. Cost-effectiveness and cost utility analyses were conducted from a societal perspective. RESULTS: The mean cost of the p-EVES intervention was L448. Carer costs were L30 (4.46 hr) less for the p-EVES intervention compared with the LVA only control. The mean difference in total costs was L417. Bootstrapping gave an incremental cost-effectiveness ratio (ICER) of L736 (95% CI L481 to L1525) for a 7% improvement in near vision visual function. Cost per quality-adjusted life year (QALY) ranged from L56 991 (lower 95% CI = L19 801) to L66 490 (lower 95% CI = L23 055). Sensitivity analysis varying the commercial price of the p-EVES device reduced ICERs by up to 75%, with cost per QALYs falling below L30 000. CONCLUSION: Portable electronic vision enhancement system (p-EVES) devices are likely to be a cost-effective use of healthcare resources for improving near vision visual function, but this does not translate into cost-effective improvements in quality of life, capability or well-being. PMID- 27682986 TI - Urinary incontinence and mortality among older adults residing in care homes. AB - AIM: To assess the association between baseline urinary incontinence and long term, all-cause mortality. BACKGROUND: Urinary incontinence is a common disorder among older institutionalised adults, with important consequences for morbidity and quality of life. Moreover, while it is a consistent mortality marker, the extent to which this association might be causal remains controversial. DESIGN: A cohort study. METHODS: We conducted a mortality follow-up study on a cohort of 675 nursing-home residents in the city of Madrid (Spain), from their 1998-1999 baseline interviews to September 2013. Study subjects or their caregivers were asked whether the resident had experienced any involuntary leakage of urine in the preceding 14 days, with subjects being subsequently defined as continent, mildly incontinent, or severely incontinent. Hazard ratios for all-cause mortality were estimated using Cox proportional hazards models. RESULTS: After a 4061 person-year follow-up (median/maximum of 4.6/15.2 years), 576 participants had died. In fully-adjusted models, urinary incontinence was associated with a 24 per cent increased risk of all-cause mortality. There was a graded relationship across severity levels, with hazard ratios 7% higher for mild and 44% higher for severe incontinence as compared with the continent group. The adjusted mortality fraction attributable to urinary incontinence was 11 per cent. CONCLUSION: It would appear that urinary incontinence is not only a marker but also a real determinant of survival in the institutionalized population. This finding, which seems plausible in a population of frail older adults, warrants further research into mechanisms that could help to elucidate this hypothesis. PMID- 27682984 TI - Proteomics insights into DNA damage response and translating this knowledge to clinical strategies. AB - Genomic instability is a critical driver in the process of cancer formation. At the same time, inducing DNA damage by irradiation or genotoxic compounds constitutes a key therapeutic strategy to kill fast-dividing cancer cells. Sensing of DNA lesions initiates a complex set of signalling pathways, collectively known as the DNA damage response (DDR). Deciphering DDR signalling pathways with high-throughput technologies could provide insights into oncogenic transformation, metastasis formation and therapy responses, and could build a basis for better therapeutic interventions in cancer treatment. Mass spectrometry (MS)-based proteomics emerged as a method of choice for global studies of proteins and their posttranslational modifications (PTMs). MS-based studies of the DDR have aided in delineating DNA damage-induced signalling responses. Those studies identified changes in abundance, interactions and modification of proteins in the context of genotoxic stress. Here we review ground-breaking MS based proteomics studies, which analysed changes in protein abundance, protein protein and protein-DNA interactions, phosphorylation, acetylation, ubiquitylation, SUMOylation and Poly(ADP-ribose)ylation (PARylation) in the DDR. Finally, we provide an outlook on how proteomics studies of the DDR could aid clinical developments on multiple levels. PMID- 27682988 TI - Congenital diaphragmatic hernia in 22q11.2 deletion syndrome. AB - We report the important association of congenital diaphragmatic hernia (CDH) and 22q11.2 deletion syndrome (22q11.2DS). The prevalence of CDH in our cohort of patients with 22q11.2DS is 0.8% (10/1246), which is greater than in the general population (0.025%). This observation suggests that 22q11.2DS should be considered when a child or fetus presents with CDH, in particular when other clinical findings associated with the 22q11.2DS are present, such as congenital cardiac defects. Furthermore, this finding may lead to the identification of an additional locus for diaphragmatic hernia in the general population. (c) 2016 Wiley Periodicals, Inc. PMID- 27682987 TI - Oxidative Stress in Wild Boars Naturally and Experimentally Infected with Mycobacterium bovis. AB - Reactive oxygen and nitrogen species (ROS-RNS) are important defence substances involved in the immune response against pathogens. An excessive increase in ROS RNS, however, can damage the organism causing oxidative stress (OS). The organism is able to neutralise OS by the production of antioxidant enzymes (AE); hence, tissue damage is the result of an imbalance between oxidant and antioxidant status. Though some work has been carried out in humans, there is a lack of information about the oxidant/antioxidant status in the presence of tuberculosis (TB) in wild reservoirs. In the Mediterranean Basin, wild boar (Sus scrofa) is the main reservoir of TB. Wild boar showing severe TB have an increased risk to Mycobacterium spp. shedding, leading to pathogen spreading and persistence. If OS is greater in these individuals, oxidant/antioxidant balance in TB-affected boars could be used as a biomarker of disease severity. The present work had a two-fold objective: i) to study the effects of bovine TB on different OS biomarkers (namely superoxide dismutase (SOD), catalasa (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and thiobarbituric acid reactive substances (TBARS)) in wild boar experimentally challenged with Mycobacterium bovis, and ii) to explore the role of body weight, sex, population and season in explaining the observed variability of OS indicators in two populations of free-ranging wild boar where TB is common. For the first objective, a partial least squares regression (PLSR) approach was used whereas, recursive partitioning with regression tree models (RTM) were applied for the second. A negative relationship between antioxidant enzymes and bovine TB (the more severe lesions, the lower the concentration of antioxidant biomarkers) was observed in experimentally infected animals. The final PLSR model retained the GPX, SOD and GR biomarkers and showed that 17.6% of the observed variability of antioxidant capacity was significantly correlated with the PLSR X's component represented by both disease status and the age of boars. In the samples from free-ranging wild boar, however, the environmental factors were more relevant to the observed variability of the OS biomarkers than the TB itself. For each OS biomarker, each RTM was defined as a maximum by one node due to the population effect. Along the same lines, the ad hoc tree regression on boars from the population with a higher prevalence of severe TB confirmed that disease status was not the main factor explaining the observed variability in OS biomarkers. It was concluded that oxidative damage caused by TB is significant, but can only be detected in the absence of environmental variation in wild boar. PMID- 27682989 TI - Takete and Maluma in Action: A Cross-Modal Relationship between Gestures and Sounds. AB - Despite Saussure's famous observation that sound-meaning relationships are in principle arbitrary, we now have a substantial body of evidence that sounds themselves can have meanings, patterns often referred to as "sound symbolism". Previous studies have found that particular sounds can be associated with particular meanings, and also with particular static visual shapes. Less well studied is the association between sounds and dynamic movements. Using a free elicitation method, the current experiment shows that several sound symbolic associations between sounds and dynamic movements exist: (1) front vowels are more likely to be associated with small movements than with large movements; (2) front vowels are more likely to be associated with angular movements than with round movements; (3) obstruents are more likely to be associated with angular movements than with round movements; (4) voiced obstruents are more likely to be associated with large movements than with small movements. All of these results are compatible with the results of the previous studies of sound symbolism using static images or meanings. Overall, the current study supports the hypothesis that particular dynamic motions can be associated with particular sounds. Building on the current results, we discuss a possible practical application of these sound symbolic associations in sports instructions. PMID- 27682990 TI - Reflux monitoring in children. AB - Recently, multichannel intraluminal impedance (MII) monitoring was added to the repertoire of tests to evaluate the (patho)physiology of gastroesophageal reflux (GER) in children. Its advantage above the sole monitoring of the esophageal pH lies in the ability of the detection of both acid and nonacid GER and to discern between liquid and gas GER. Currently, combined 24 h pH-MII monitoring is recommended for evaluation of gastro-esophageal reflux disease (GERD) and its relation to symptoms in infants and children, despite the lack of reference values in these age groups. There is new evidence in the current issue of this Journal supporting the role of pH-MII monitoring for the evaluation of children presenting with gastrointestinal symptoms suggestive of GERD and the prediction of the presence of reflux esophagitis. However, several issues should be taken into account when performing pH-MII clinically. PMID- 27682991 TI - Erratum. PMID- 27682992 TI - Radiative heat transfer exceeding the blackbody limit between macroscale planar surfaces separated by a nanosize vacuum gap. AB - Using Rytov's fluctuational electrodynamics framework, Polder and Van Hove predicted that radiative heat transfer between planar surfaces separated by a vacuum gap smaller than the thermal wavelength exceeds the blackbody limit due to tunnelling of evanescent modes. This finding has led to the conceptualization of systems capitalizing on evanescent modes such as thermophotovoltaic converters and thermal rectifiers. Their development is, however, limited by the lack of devices enabling radiative transfer between macroscale planar surfaces separated by a nanosize vacuum gap. Here we measure radiative heat transfer for large temperature differences (~120 K) using a custom-fabricated device in which the gap separating two 5 * 5 mm2 intrinsic silicon planar surfaces is modulated from 3,500 to 150 nm. A substantial enhancement over the blackbody limit by a factor of 8.4 is reported for a 150-nm-thick gap. Our device paves the way for the establishment of novel evanescent wave-based systems. PMID- 27682993 TI - Resonantly Enhanced Emission from a Luminescent Nanostructured Waveguide. AB - Controlling the characteristics of photon emission represents a significant challenge for both fundamental science and device technologies. Research on microcavities, photonic crystals, and plasmonic nanocavities has focused on controlling spontaneous emission by way of designing a resonant structure around the emitter to modify the local density of photonic states. In this work, we demonstrate resonantly enhanced emission using luminescent nanostructured waveguide resonance (LUNAR). Our concept is based on coupling between emitters in the luminescent waveguide and a resonant waveguide mode that interacts with a periodic nanostructure and hence outcouples via diffraction. We show that the enhancement of resonance emission can be controlled by tuning the design parameters. We also demonstrate that the enhanced emission is attributable to the accelerated spontaneous emission rate that increases the probability of photon emission in the resonant mode, accompanied by enhanced the local density of photonic states. This study demonstrates that nanostructured luminescent materials can be designed to exhibit functional and enhanced emission. We anticipate that our concept will be used to improve the performance of a variety of photonic and optical applications ranging from bio/chemical sensors to lighting, displays and projectors. PMID- 27682995 TI - Prader-Willi syndrome mental health research strategy workshop proceedings: the state of the science and future directions. AB - : This paper reports on the 'Prader-Willi Syndrome (PWS) Mental Health Research Strategy Workshop' that took place in March 2015. PWS is characterized by a complex phenotype affecting multiple systems with a high prevalence of maladaptive behaviours, and neuropsychiatric illness. Prader Willi syndrome results from the absence of paternally derived alleles located at the imprinted chromosomal locus, 15q11-13. The goal of the workshop was to highlight the state of the science of the mental health of people with this rare neurodevelopmental disorder. Mental ill health and maladaptive behaviors significantly impact quality of life for persons with PWS and their caregivers. Effective treatments and further research into this area are critically needed. METHODS: A multidisciplinary group of scientists and health care professionals were brought together to discuss the mental health and behavioral needs of people with PWS. The workshop strategy was to integrate established work on PWS with other relevant areas of study. The meeting also focused on two neurobiological systems that research had suggested were relevant to understanding the broader mental health aspects of PWS: the autonomic nervous system and oxytocin/vasopressin pathways. Other relevant topics were considered and recommendations made. RESULTS: The workshop presentations and working group discussions revealed that no one approach was sufficient to fully conceptualize the mental health challenges in PWS. Workshop discussions pointed to the need for theoretically informed studies focused on clinical characterization, measurement, and the probing of specific neurobiological systems through pharmaceutical or other interventions. Future studies in this area should explore the use of advanced neuroimaging protocols, as well as molecular studies using iPS cells in order to create more informed theories. CONCLUSIONS: Within this framework, workshop participants identified and prioritized key research questions, and highlighted current opportunities. Recommendations were made with respect to the development of specific resources and tools for furthering mental health research such as The Global PWS Registry, the development of effective endpoints, the use of animal models and iPS cells to aid understanding of the neurobiological underpinnings. Additionally, collaborative opportunities across disciplines and syndromes were highlighted and targeted research initiatives focused on psychological/behavioral interventions modified for use in PWS were recommended. PMID- 27682996 TI - Delayed gadolinium-enhanced MRI of meniscus (dGEMRIM) and cartilage (dGEMRIC) in healthy knees and in knees with different stages of meniscus pathology. AB - BACKGROUND: Lesions in the meniscus are risk factors for developing knee osteoarthritis (OA), not least because of the role of the meniscus in the pathological progression of OA. Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) has extensively been used to identify pre-radiographic cartilage changes in OA. In contrast, its counterpart with regard to examination of the meniscus, gadolinium enhanced MRI of meniscus (dGEMRIM), has been less utilized. In this study we use 3D dGEMRIM in patients with meniscus lesions and compare them with previous results of healthy individuals. METHODS: Eighteen subjects with MRI-verified posteromedial meniscus lesions and 12 healthy subjects with non injured and non-symptomatic knee joints, together 30 volunteers, were examined using 3D Look-Locker sequence after intravenous injection of Gd-DTPA2- (0.2 mmol/kg body weight). Relaxation time (T1) was measured in the posterior meniscus and femoral cartilage before and 60, 90, 120 and 180 min after injection. Relaxation rate (R1 = 1/T1) and change in relaxation rate (DeltaR1) were calculated. For statistical analyses, Student's t-test and Analysis of Variance (ANOVA) were used. RESULTS: The pre-contrast diagnostic MRI identified two sub cohorts in the 18 patients with regard to meniscus injury: 1) 11 subjects with MRI verified pathological intrameniscal changes (grade 2) in the posteromedial meniscus only and no obvious cartilage changes. The lateral meniscus showed no pathology. 2) 7 subjects with MRI verified pathological rupture (grade 3) of the posteromedial meniscus and pathological changes in the lateral meniscus and/or medial and lateral joint cartilage. Comparisons of pathological and healthy posteromedial meniscus revealed opposite patterns in both T1Gd and DeltaR1 values between pathological meniscus grade 2 and grade 3. The concentration of the contrast agent was lower than in healthy meniscus in grade 2 lesions (p = 0.046) but tended to increase in grade 3 lesions (p = 0.110). Maximum concentration of contrast agent was reached after 180 min in both cartilage and menisci (except for grade 3 menisci where the maximum concentration was reached after 90 min). CONCLUSION: dGEMRIM and dGEMRIC may be feasible to combine in vivo, preferably with one examination before and one 2 h after contrast injection. Possible different dGEMRIM patterns at different stages of meniscus lesions must be taken into account when evaluating meniscus pathology. PMID- 27682998 TI - Fluorescent Angiography Used to Evaluate the Perfusion Status of Anastomosis in Laparoscopic Anterior Resection. AB - BACKGROUND: Anastomotic leakage after gastrointestinal surgery is associated with significant morbidity and mortality.1 Insufficient vascular supply is one cause.2 Recent reports of using intraoperative indocyanine green (ICG) fluorescent angiography to evaluate whether perfusion of the anastomosis is adequate has yielded positive outcomes.3 - 6 The authors describe their use of ICG-enhanced fluorescence angiography in a laparoscopic anterior resection. METHODS: The patient was an 80-year-old with an upper rectal adenocarcinoma and significant cardiovascular risk factors. Fluorescence angiography with 0.4 mg/kg of ICG was administered intravenously just before the colorectal anastomosis was fashioned. A near-infrared (NIR) laparoscopic camera (KARLSTORZ, GmbH & Co. KG, Tuttlingen, Germany) was used to inspect the anastomosis. For this video, 0.4 mg/kg of ICG also was injected after ligation of the inferior mesenteric artery to demonstrate the appearance of a poorly perfused sigmoid bowel. RESULTS: Just before the staple was fired to fashion the colorectal anastomosis, an intravenous bolus of ICG was administered. Within seconds, vessels on both ends of the anastomosis turned fluorescent blue, indicating adequacy of perfusion. The use of ICG did not significantly lengthen the operative time (285 min) because its effect appeared within seconds after its administration. The patient recovered well and was discharged on postoperative day 5. Another four patients who also underwent intraoperative fluorescent angiography for left-sided colorectal lesions did not experience anastomotic leakage. CONCLUSION: The study showed that ICG fluorescent angiography is a simple and quick intraoperative tool for evaluating the perfusion of the anastomosis. The authors' experience with ICG fluorescent angiography has shown promising results, with a 0 % anastomotic leak rate. PMID- 27682997 TI - Lumican negatively controls the pathogenicity of murine encephalitic TH17 cells. AB - TH17 cells play an essential role in the development of both human multiple sclerosis and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, it is not well understood how the pathogenicity of TH17 cells is controlled in the autoimmune neuroinflammation. In vitro, we found Lumican (Lum), an extracellular matrix (ECM) protein, is selectively expressed by TH17 cells among tested murine TH subsets. Lum deficiency leads to earlier onset and enhanced severity of EAE. This enhanced disease in Lum-deficient mice is associated with increased production of IL-17 and IL-21 and decreased TH17 cell apoptosis. Dysregulation in cytokine production appears to be specific to TH17 cells as TH1 and TH2 cell polarization and/or cytokine production were unaltered. Furthermore, adoptive transfer of myelin oligodendrocyte glycoprotein specific TH17 cells derived from Lum-deficient mice led to earlier onset and increased severity of disease compared to controls highlighting a TH17-cell-intrinsic effect of Lum. Taken together, our results suggest that Lum negatively regulates encephalitic TH17 cells, implicating a potential therapeutic pathway in TH17 cell mediated autoimmune and inflammatory diseases. PMID- 27682999 TI - Laparoscopic Right Hepatectomy: Toward Protocolization and Simplification. AB - BACKGROUND: Major hurdles for laparoscopic right hepatectomy (LapRH) include difficulties in (1) mobilization and (2) applying hanging maneuver and (3) lack of experienced assistants. We discuss the protocolization of lapRH, introducing our simplified technique. METHODS: The procedure was disassembled into six steps: (1) curtailed mobilization of the right liver so as to align the resection plane with the laparoscopic camera view, (2) inflow vascular control, (3) setting up the parenchymal resection applying the rubber band retraction method, (4) parenchymal resection approaching the caudate lobe, (5) a lifting-up maneuver using a laparoscopic grasper or retractor instead of the hanging maneuver, and (6) completion of resection dividing the caudate lobe, right hepatic vein, and remaining ligament. RESULTS: Between March 2014 and August 2015, 13 LapRH surgeries were attempted. The patients consisted of eight males and five females with a mean age of 58.5 +/- 11.6 years. Final pathological diagnoses were hepatocellular carcinoma in seven patients, intrahepatic duct stone in 4, and colorectal liver metastasis in 2. The mean total operative time was 381 +/- 66 minutes, and the mean intraoperative estimated blood loss was 633 +/- 619 ml. One patient was converted to open surgery. There was no clinically significant complication, and the mean length of stay after surgery was 9.1 +/- 2.3 days. CONCLUSIONS: Protocolization and simplification of the procedure may allow professionals to better understand the respective process and determine appropriate port placements, resulting in safe and successful minimally invasive hepatectomy procedures. PMID- 27683000 TI - Auditory mechanics in a bush-cricket: direct evidence of dual sound inputs in the pressure difference receiver. AB - The ear of the bush-cricket, Copiphora gorgonensis, consists of a system of paired eardrums (tympana) on each foreleg. In these insects, the ear is backed by an air-filled tube, the acoustic trachea (AT), which transfers sound from the prothoracic acoustic spiracle to the internal side of the eardrums. Both surfaces of the eardrums of this auditory system are exposed to sound, making it a directionally sensitive pressure difference receiver. A key feature of the AT is its capacity to reduce the velocity of sound propagation and alter the acoustic driving forces at the tympanum. The mechanism responsible for reduction in sound velocity in the AT remains elusive, yet it is deemed to depend on adiabatic or isothermal conditions. To investigate the biophysics of such multiple input ears, we used micro-scanning laser Doppler vibrometry and micro-computed X-ray tomography. We measured the velocity of sound propagation in the AT, the transmission gains across auditory frequencies and the time-resolved mechanical dynamics of the tympanal membranes in C. gorgonensis Tracheal sound transmission generates a gain of approximately 15 dB SPL, and a propagation velocity of ca 255 m s-1, an approximately 25% reduction from free field propagation. Modelling tracheal acoustic behaviour that accounts for thermal and viscous effects, we conclude that reduction in sound velocity within the AT can be explained, among others, by heat exchange between the sound wave and the tracheal walls. PMID- 27683001 TI - Molecular stripping, targets and decoys as modulators of oscillations in the NF kappaB/IkappaBalpha/DNA genetic network. AB - Eukaryotic transcription factors in the NF-kappaB family are central components of an extensive genetic network that activates cellular responses to inflammation and to a host of other external stressors. This network consists of feedback loops that involve the inhibitor IkappaBalpha, numerous downstream functional targets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-kappaB becomes oscillatory, and temporal patterns of NF-kappaB pulses appear to govern the patterns of downstream gene expression needed for immune response. Understanding how the information from external stress passes to oscillatory signals and is then ultimately relayed to gene expression is a general issue in systems biology. Recently, in vitro kinetic experiments as well as molecular simulations suggest that active stripping of NF-kappaB by IkappaBalpha from its binding sites can modify the traditional systems biology view of NF-kappaB/IkappaBalpha gene circuits. In this work, we revise the commonly adopted minimal model of the NF kappaB regulatory network to account for the presence of the large number of binding sites for NF-kappaB along with dissociation from these sites that may proceed either by passive unbinding or by active molecular stripping. We identify regimes where the kinetics of target and decoy unbinding and molecular stripping enter a dynamic tug of war that may either compensate each other or amplify nuclear NF-kappaB activity, leading to distinct oscillatory patterns. Our finding that decoys and stripping play a key role in shaping the NF-kappaB oscillations suggests strategies to control NF-kappaB responses by introducing artificial decoys therapeutically. PMID- 27683002 TI - Active inference and robot control: a case study. AB - Active inference is a general framework for perception and action that is gaining prominence in computational and systems neuroscience but is less known outside these fields. Here, we discuss a proof-of-principle implementation of the active inference scheme for the control or the 7-DoF arm of a (simulated) PR2 robot. By manipulating visual and proprioceptive noise levels, we show under which conditions robot control under the active inference scheme is accurate. Besides accurate control, our analysis of the internal system dynamics (e.g. the dynamics of the hidden states that are inferred during the inference) sheds light on key aspects of the framework such as the quintessentially multimodal nature of control and the differential roles of proprioception and vision. In the discussion, we consider the potential importance of being able to implement active inference in robots. In particular, we briefly review the opportunities for modelling psychophysiological phenomena such as sensory attenuation and related failures of gain control, of the sort seen in Parkinson's disease. We also consider the fundamental difference between active inference and optimal control formulations, showing that in the former the heavy lifting shifts from solving a dynamical inverse problem to creating deep forward or generative models with dynamics, whose attracting sets prescribe desired behaviours. PMID- 27683003 TI - Optimizing dual energy cone beam CT protocols for preclinical imaging and radiation research. AB - OBJECTIVE: The aim of this work was to investigate whether quantitative dual energy CT (DECT) imaging is feasible for small animal irradiators with an integrated cone-beam CT (CBCT) system. METHODS: The optimal imaging protocols were determined by analyzing different energy combinations and dose levels. The influence of beam hardening effects and the performance of a beam hardening correction (BHC) were investigated. In addition, two systems from different manufacturers were compared in terms of errors in the extracted effective atomic numbers (Zeff) and relative electron densities (rhoe) for phantom inserts with known elemental compositions and relative electron densities. RESULTS: The optimal energy combination was determined to be 50 and 90 kVp. For this combination, Zeff and rhoe can be extracted with a mean error of 0.11 and 0.010, respectively, at a dose level of 60 cGy. CONCLUSION: Quantitative DECT imaging is feasible for small animal irradiators with an integrated CBCT system. To obtain the best results, optimizing the imaging protocols is required. Well-separated X ray spectra and a sufficient dose level should be used to minimize the error and noise for Zeff and rhoe. When no BHC is applied in the image reconstruction, the size of the calibration phantom should match the size of the imaged object to limit the influence of beam hardening effects. No significant differences in Zeff and rhoe errors are observed between the two systems from different manufacturers. Advances in knowledge: This is the first study that investigates quantitative DECT imaging for small animal irradiators with an integrated CBCT system. PMID- 27683004 TI - The oculomotor salience of flicker, apparent motion and continuous motion in saccade trajectories. AB - The aim of the present study was to investigate the impact of dynamic distractors on the time-course of oculomotor selection using saccade trajectory deviations. Participants were instructed to make a speeded eye movement (pro-saccade) to a target presented above or below the fixation point while an irrelevant distractor was presented. Four types of distractors were varied within participants: (1) static, (2) flicker, (3) rotating apparent motion and (4) continuous motion. The eccentricity of the distractor was varied between participants. The results showed that saccadic trajectories curved towards distractors presented near the vertical midline; no reliable deviation was found for distractors presented further away from the vertical midline. Differences between the flickering and rotating distractor were found when distractor eccentricity was small and these specific effects developed over time such that there was a clear differentiation between saccadic deviation based on apparent motion for long-latency saccades, but not short-latency saccades. The present results suggest that the influence on performance of apparent motion stimuli is relatively delayed and acts in a more sustained manner compared to the influence of salient static, flickering and continuous moving stimuli. PMID- 27683005 TI - Responses to affective pictures depicting humans: late positive potential reveals a sex-related effect in processing that is not present in subjective ratings. AB - We examined sex-related effects in the amplitudes of the late positive potential (LPP), an event-related potential elicited by the presentation of emotional stimuli. Sixteen females and 18 males viewed emotional pictures to perform a visual detection task. In female participants, viewing unpleasant pictures elicited larger LPP (550-900 ms) when the pictures contained humans (human pictures) than when they did not contain humans (non-human pictures). For male participants, the results were reversed, with smaller LPP for unpleasant human pictures. Subjective ratings of valence in both female and male participants showed that unpleasant human pictures were evaluated less negatively than unpleasant non-human pictures. The results indicate that greater LPP amplitude for human than for non-human pictures occurred in females irrespective of subjective evaluations. This suggests that relatively robust processes in females cause sex-related effects in sensitivity to human pictures. PMID- 27683008 TI - Appendicitis caused by the metastasis of HER2-positive breast cancer. AB - The appropriate therapy for metastatic breast cancer must be selected based on the immunohistochemical phenotype of the cancer. However, biopsy for metastatic lesions is difficult. We herein report a patient with incidental appendicitis caused by a metastatic breast cancer which was successfully treated with effective therapy chosen based on the pathological diagnosis obtained on resection. The patient was a 56-year-old female with right breast cancer and an immunohistochemical status of estrogen receptor (ER) (+), progesterone receptor (PgR) (+), human epidermal growth factor receptor 2 (HER2) (3+), and Ki67 40 %. She received epirubicin and cyclophosphamide therapy followed by docetaxel and trastuzumab, and total mastectomy with axillary dissection was performed. Thereafter, she received postmastectomy radiation, adjuvant trastuzumab, and adjuvant hormone therapy with letrozole. One year and 8 months after the operation, she developed right hydronephrosis and swollen para-aortic lymph nodes and her hormone therapy was changed to fulvestrant therapy. However, she additionally developed left hydronephrosis and multiple bone metastases, and pertuzumab, trastuzumab, and docetaxel therapy was started. After six cycles, her disease became well-controlled, and maintenance with pertuzumab and trastuzumab was introduced. However, after another 7 months, she developed new vertebral metastasis and acute appendicitis and laparoscopic appendectomy was performed. A pathological investigation of the resected appendix revealed some clusters of atypical cells in the subserosa and muscle layer, which showed an immunohistochemical status of ER (+), PgR (-), HER2 (3+), and E-cadherin (-). These findings led to the diagnosis as appendiceal metastasis of invasive lobular carcinoma (ILC) from the breast. Thereafter, she received trastuzumab-DM1 and her disease was well-controlled again. Appendicitis caused by breast cancer is very rare. However, ILC sometimes develops metastases in the abdominal cavity; an appendiceal tumor should therefore be included in the differential diagnosis. A pathological diagnosis of metastatic tumor could be very useful for selecting the effective therapy. PMID- 27683007 TI - Peroxynitrite formed during a transient episode of brain ischaemia increases endothelium-derived hyperpolarization-type dilations in thromboxane/prostaglandin receptor-stimulated rat cerebral arteries. AB - AIM: Increased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium-derived hyperpolarization (EDH). We investigated whether EDH-type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influence of peroxynitrite. METHODS: Vascular function was determined by wire myography after TP stimulation with the thromboxane A2 mimetic 9,11-dideoxy-9alpha, 11alpha -methano-epoxy prostaglandin F2alpha (U46619) in MCA of Sprague Dawley rats subjected to MCA occlusion (90 min)/reperfusion (24 h) or sham operation, and in non-operated (control) rats. Some rats were treated with saline or the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (20 mg kg-1 ). Protein expression was evaluated in MCA and in human microvascular endothelial cells submitted to hypoxia (overnight)/reoxygenation (24 h) (H/R) using immunofluorescence and immunoblotting. RESULTS: In U46619-pre-constricted MCA, EDH-type relaxation by the proteinase-activated receptor 2 agonist serine-leucine isoleucine-glycine-arginine-leucine-NH2 (SLIGRL) was greater in I/R than sham rats due to an increased contribution of small-conductance calcium-activated potassium channels (SKCa ), which was confirmed by the enlarged relaxation to the SKCa activator N-cyclohexyl-N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4 pyrimidinamine. I/R and H/R induced endothelial protein tyrosine nitration and filamentous-actin disruption. In control MCA, either cytochalasin D or peroxynitrite disrupted endothelial filamentous-actin and augmented EDH-type relaxation. Furthermore, peroxynitrite decomposition during I/R prevented the increase in EDH-type responses. CONCLUSION: Following TP stimulation in MCA, EDH type relaxation to SLIGRL is greater after I/R due to endothelial filamentous actin disruption by peroxynitrite, which prevents TP-induced block of SKCa input to EDH. These results reveal a novel mechanism whereby peroxynitrite could promote post-ischaemic brain injury. PMID- 27683006 TI - Mapping the visual brain areas susceptible to phosphene induction through brain stimulation. AB - Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique whose effects on neural activity can be uncertain. Within the visual cortex, phosphenes are a useful marker of TMS: They indicate the induction of neural activation that propagates and creates a conscious percept. However, we currently do not know how susceptible different areas of the visual cortex are to TMS-induced phosphenes. In this study, we systematically map out locations in the visual cortex where stimulation triggered phosphenes. We relate this to the retinotopic organization and the location of object- and motion-selective areas, identified by functional magnetic resonance imaging (fMRI) measurements. Our results show that TMS can reliably induce phosphenes in early (V1, V2d, and V2v) and dorsal (V3d and V3a) visual areas close to the interhemispheric cleft. However, phosphenes are less likely in more lateral locations (hMT+/V5 and LOC). This suggests that early and dorsal visual areas are particularly amenable to TMS and that TMS can be used to probe the functional role of these areas. PMID- 27683009 TI - Non-bacterial thrombotic endocarditis in the right atrium caused by pectus excavatum. AB - BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is an uncommon pathological situation, which involves the presence of bland, fibrin-platelet thrombi. It usually occurs at the endocardium of cardiac valves, in association with endothelial injury and a hypercoagulative state. However, NBTE on the endocardium at the right atrial free wall in a patient without any apparent hypercoagulative background is rarely reported. CASE PRESENTATION: A girl aged 4 years with severe pectus excavatum was referred to our hospital for treatment of a recurrent right atrial tumor. The tumor was removed concomitant with pectus excavatum repair. The tumor was revealed as recurrent thrombus. Pathological findings showed that NBTE caused by an operative scar on the endocardium of the right atrium and sustained rheological stress in the right atrium due to compression from pectus excavatum lead to recurrent thrombus formation. Three years after the discontinuation of anticoagulation therapy, no sign of thrombus formation was found. CONCLUSIONS: To our knowledge, this is the first report of NBTE related to an interaction between sustained rheological stress from cardiac compression and endocardial injury. In such patients, we recommend concomitant chest wall repair when the operative scar is present at the site of the rheological force. PMID- 27683010 TI - The effects of a genome-wide supported variant in the CACNA1C gene on cortical morphology in schizophrenia patients and healthy subjects. AB - Schizophrenia is a highly heritable disorder with multiple susceptibility genes. Previously, we identified CACNA1C rs2007044 as a new risk locus for schizophrenia, with the minor allele G as risk allele. This association was recently validated by a powerful genome-wide association study. However, the underlying neural mechanisms remain unclear. Therefore, we tested whether the risk allele has an influence on cortical surface area and thickness in a sample of schizophrenia patients and healthy controls. We found significant genotype by diagnosis interactions on cortical surface area, but not thickness, in the right dorsolateral prefrontal cortex and the left superior parietal cortex, both of which are key components of the central executive network. Moreover, the surface areas of both regions were inversely correlated with PANSS negative scores in AA homogeneous patients but not in G-carriers. This is the first study to describe the influence of the new genome-wide supported schizophrenia risk variant on cortical morphology. Our data revealed a significant genetic effect of cortical surface area in pivotal brain regions, which have been implicated in the pathophysiology of schizophrenia, possibly via their involvement in cognitive functions. These results yield new insights into the potential neural mechanisms linking CACNA1C to the risk of schizophrenia. PMID- 27683011 TI - Compliance, illiteracy and low-protein diet: multiple challenges in CKD and a case of self-empowerment. AB - BACKGROUND: Low-protein diets (LPD) are an important means of delaying the need for dialysis and attaining a stable metabolic balance in chronic kidney disease (CKD). Many authors consider a low educational level and illiteracy to be adverse features for a good dietary compliance. CASE PRESENTATION: We report the case of a 77-year old woman, illiterate, affected by advanced CKD (stage 4 according to KDIGO guidelines). She was initially ashamed of her problem and did not declare it, leading to an overzealous reduction in protein intake. However, with her daughter's help, who translated the dietary prescription into images, she overcame the barrier represented by illiteracy and was able to correctly follow the prescriptions, attaining good kidney function stability and preserving an adequate nutritional status. CONCLUSIONS: The case underlines the importance of a personalized approach to dietary prescriptions and suggests that it is possible to achieve a good compliance to the dietary treatment of CKD also in patients with relevant cultural barriers. PMID- 27683012 TI - Molecular Basis for Inhibition of the Na+/Citrate Transporter NaCT (SLC13A5) by Dicarboxylate Inhibitors. AB - The Na+/citrate transporter, NaCT (SLC13A5), is a therapeutic target for metabolic diseases. Citrate is an important signaling molecule that regulates the activity of lipid- and glucose-metabolizing enzymes in cells. Previous studies identified two compounds, PF-06649298 (compound 2: ) and PF-06678419 (compound 4: ), that inhibit human NaCT with high affinity, and one of the compounds demonstrated specificity relative to other SLC13 family members. Here we use molecular modeling and site-directed mutagenesis of hNaCT followed by transport characterization and cell-surface biotinylation to examine the residues involved in inhibitor binding and transport. The results indicate that residues located near the putative citrate binding site, G228, V231, V232, and G409, affect both citrate transport and inhibition of citrate uptake by compounds 2: and 4: V231 appears to distinguish between compounds 2: and 4: as inhibitors. Furthermore, residues located outside of the putative citrate binding site, Q77 and T86, may also play a role in NaCT inhibition by compounds 2: and 4: Our results provide new insight into the mechanism of transport and inhibition in NaCT and the SLC13 family. These findings should provide a basis for future drug design of SLC13 inhibitors. PMID- 27683013 TI - Role of the Second Extracellular Loop of the Adenosine A1 Receptor on Allosteric Modulator Binding, Signaling, and Cooperativity. AB - Allosteric modulation of adenosine A1 receptors (A1ARs) offers a novel therapeutic approach for the treatment of numerous central and peripheral disorders; however, despite decades of research, there is a relative paucity of structural information regarding the A1AR allosteric site and mechanisms governing cooperativity with orthosteric ligands. We combined alanine-scanning mutagenesis of the A1AR second extracellular loop (ECL2) with radioligand binding and functional interaction assays to quantify effects on allosteric ligand affinity, cooperativity, and efficacy. Docking and molecular dynamics (MD) simulations were performed using an A1AR homology model based on an agonist-bound A2AAR structure. Substitution of E172ECL2 for alanine reduced the affinity of the allosteric modulators PD81723 and VCP171 for the unoccupied A1AR. Residues involved in cooperativity with the orthosteric agonist NECA were different in PD81723 and VCP171; positive cooperativity between PD81723 and NECA was reduced on alanine substitution of a number of ECL2 residues, including E170ECL2 and K173ECL2, whereas mutation of W146ECL2 and W156ECL2 decreased VCP171 cooperativity with NECA. Molecular modeling localized a likely allosteric pocket for both modulators to an extracellular vestibule that overlaps with a region used by orthosteric ligands as they transit into the canonical A1AR orthosteric site. MD simulations confirmed a key interaction between E172ECL2 and both modulators. Bound PD81723 is flanked by another residue, E170ECL2, which forms hydrogen bonds with adjacent K168ECL2 and K173ECL2. Collectively, our data suggest E172ECL2 is a key allosteric ligand-binding determinant, whereas hydrogen bonding networks within the extracellular vestibule may facilitate the transmission of cooperativity between orthosteric and allosteric sites. PMID- 27683014 TI - Extracellular Loop 2 of the Adenosine A1 Receptor Has a Key Role in Orthosteric Ligand Affinity and Agonist Efficacy. AB - The adenosine A1 G protein-coupled receptor (A1AR) is an important therapeutic target implicated in a wide range of cardiovascular and neuronal disorders. Although it is well established that the A1AR orthosteric site is located within the receptor's transmembrane (TM) bundle, prior studies have implicated extracellular loop 2 (ECL2) as having a significant role in contributing to orthosteric ligand affinity and signaling for various G protein-coupled receptors (GPCRs). We thus performed extensive alanine scanning mutagenesis of A1AR-ECL2 to explore the role of this domain on A1AR orthosteric ligand pharmacology. Using quantitative analytical approaches and molecular modeling, we identified ECL2 residues that interact either directly or indirectly with orthosteric agonists and antagonists. Discrete mutations proximal to a conserved ECL2-TM3 disulfide bond selectively affected orthosteric ligand affinity, whereas a cluster of five residues near the TM4-ECL2 juncture influenced orthosteric agonist efficacy. A combination of ligand docking, molecular dynamics simulations, and mutagenesis results suggested that the orthosteric agonist 5'-N-ethylcarboxamidoadenosine binds transiently to an extracellular vestibule formed by ECL2 and the top of TM5 and TM7, prior to entry into the canonical TM bundle orthosteric site. Collectively, this study highlights a key role for ECL2 in A1AR orthosteric ligand binding and receptor activation. PMID- 27683016 TI - Spatial Prediction and Optimized Sampling Design for Sodium Concentration in Groundwater. AB - Sodium is an integral part of water, and its excessive amount in drinking water causes high blood pressure and hypertension. In the present paper, spatial distribution of sodium concentration in drinking water is modeled and optimized sampling designs for selecting sampling locations is calculated for three divisions in Punjab, Pakistan. Universal kriging and Bayesian universal kriging are used to predict the sodium concentrations. Spatial simulated annealing is used to generate optimized sampling designs. Different estimation methods (i.e., maximum likelihood, restricted maximum likelihood, ordinary least squares, and weighted least squares) are used to estimate the parameters of the variogram model (i.e, exponential, Gaussian, spherical and cubic). It is concluded that Bayesian universal kriging fits better than universal kriging. It is also observed that the universal kriging predictor provides minimum mean universal kriging variance for both adding and deleting locations during sampling design. PMID- 27683015 TI - Income and Technology as Drivers of Australian Healthcare Expenditures. AB - The roles of income and technology as the major determinants of aggregate healthcare expenditure (HEXP) continue to interest economists and health policy researchers. Concepts and measures of medical technologies remain complex; however, income (on the demand side) and technology (on the supply side) are important drivers of HEXP. This paper presents analysis of Australia's HEXP, using time-series econometrics modeling techniques applied to 1971-2011 annual aggregate data. Our work fills two important gaps in the literature. First, we model the determinants of Australia's HEXP using the latest and longest available data series. Second, this novel study investigates several alternative technology proxies (input and output measures), including economy-wide research and development expenditures, hospital research expenditures, mortality rate, and two technology indexes based on medical devices. We then apply the residual component method and the technology proxy approach to quantify the technology effects on HEXP. Our empirical results suggest that Australian aggregate healthcare is a normal good and a technical necessity with the income elasticity estimates ranging from 0.51 to 0.97, depending on the model. The estimated technology effects on HEXP falling in the 0.30-0.35 range and mimicking those in the literature using the US data, reinforce the global spread of healthcare technology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27683017 TI - Black veins: a case of minocycline-induced pigmentation post-sclerotherapy and a review of literature. AB - Minocycline-induced pigmentation (MIP) is an uncommon but well-described adverse effect of oral minocycline treatment. MIP is clinically and histopathologically distinct from post-sclerotherapy pigmentation. We report a case of a patient presenting with blackened skin overlying veins recently treated with endovenous laser and foam sclerotherapy. The patient was a 44-year-old male with systemic sclerosis who commenced minocycline for the treatment of rosacea 5 months prior. Histological examination of the discolored tissue and underlying vein revealed hemosiderin deposition in the dermis and pigmented macrophages within the sub endothelial layer of the vein wall with a staining pattern consistent with MIP. Venous tissue has not previously been reported in the literature as a target of minocycline pigmentation. Our patient preferred to control his rosacea by continuing to take minocycline. Follow-up ultrasound examinations revealed the treated vessels to be fully occluded with no evidence of recanalization, residual flow or ongoing thrombophlebitis. Despite a good sclerotherapy outcome, the pigmentation did not subside over 2 years. This case demonstrates that oral minocycline may induce significant and potentially long-term pigmentation in predisposed patients undergoing sclerotherapy. PMID- 27683018 TI - Feasibility and Acceptability of Smartphone Assessment in Older Adults with Cognitive and Emotional Difficulties. AB - OBJECTIVES: Ecological momentary assessment (EMA) has several advantages in clinical research yet little is known about the feasibility of collecting EMA data with mobile technologies in older adults, particularly those with emotional or cognitive difficulties. The aim of this feasibility study was to assess perceived acceptability, adherence rates, and reasons for non-adherence to smartphone-based EMA. METHOD: At two sites, participants (n=103) aged 65 years or older with a DSM-IV-defined anxiety or depressive disorder and cognitive concerns responded three times daily to smartphone-based EMA questions assessing clinical outcomes for two 10-day periods. Quantitative and qualitative measures assessed acceptability, adherence, and reasons for non-adherence following both 10-day EMA periods. RESULTS: Participants were moderately satisfied with and comfortable using smartphone-based EMA. Overall, 76% of participants completed surveys on >=10 of the 20 assessment days, and 70% of participants completed at least 30% of the total surveys. Reasons for non-adherence included technical (malfunction), logistical (competing demands), physiological (hearing difficulties), and cognitive (forgetting) issues. DISCUSSION: Smartphone-based EMA is feasible in older adults with cognitive and emotional difficulties. EMA tools should be responsive to the needs and preferences of participants to ensure adequate acceptability and adherence in this population. Our findings can inform the design, development, and implementation of mobile technologies in older adults in research and clinical contexts. PMID- 27683020 TI - The Impact of Case Finding on the Recruitment Yield for COPD Research in Primary Care: An Observational Study. AB - BACKGROUND: Recruiting patients for research in primary care is difficult with diseases that tend to remain underdiagnosed, such as chronic obstructive pulmonary disease (COPD). Researchers may consider introducing case finding into patient recruitment, but the impact on recruitment yield is largely unknown. OBJECTIVES: To assess the impact of case finding on recruitment yield and population characteristics in primary care-based COPD research. METHODS: For a cluster randomized controlled trial of COPD in primary care, an opportunistic case finding strategy was introduced into patient recruitment, in addition to recruiting patients with previously diagnosed COPD. The recruitment process and performance of the primary care physicians (PCPs) were analysed. The numbers and characteristics of patients identified by case finding were compared with those of patients with previously diagnosed COPD. RESULTS: Thirty-five PCPs approached 398 patients and successfully recruited 216 patients during 1 year. The mean number of patients recruited was 6.3 (range 0-16) per PCP. Case finding contributed 71 patients (32.9%) with significantly milder disease, with FEV1 % predicted +16.7 (95% CI: +11.3 to +22.0), a COPD Assessment Test difference of -4 points (95% CI: -2 to -6; p < 0.001), and fewer exacerbations resulting in a higher rate of GOLD class A (85.9 vs. 45.5%; p < 0.001). The smoking rate was significantly higher among patients with newly diagnosed COPD (70.4 vs. 48.6%; p = 0.002). CONCLUSION: Case finding increased the number of patients recruited by 50%. The COPD patients identified by case finding differed importantly from those with previously diagnosed COPD. Researchers should be aware of COPD underdiagnosis and the potential impact of case finding during patient recruitment. PMID- 27683019 TI - A new look at nursing home residents' depressive symptoms: the role of basic versus expanded everyday competence. AB - BACKGROUND: Depressive symptoms are highly prevalent in nursing home (NH) residents. The relationship between depressive symptoms and everyday competence in terms of basic (BaCo) and expanded everyday competence (ExCo; see Baltes et al., 2001) in the NH setting is, however, not clear. Applying Lewinsohn's depression model, we examined how residents' BaCo and ExCo relate to their depressive symptoms. Furthermore, we investigated the mediating role of perceived control. METHODS: Cross-sectional data from 196 residents (M age = 83.7 years, SD = 9.4 years) of two German NHs were analyzed. Study variables were assessed by the Geriatric Depression Scale-Residential (GDS-12R), maximal gait speed (BaCo), proxy ratings of residents' in-home activity participation, and self-initiated social contact done by staff (ExCo). Structural equation modeling (SEM) was used and a simulation study was included to determine power and potential estimation bias. RESULTS: At the descriptive level, one quarter of the residents showed symptoms of depression according to the GDS-12R cut-off criterion. Residents' BaCo and ExCo were independently and equally strongly associated with their depressive symptoms in the SEM analysis. These findings were affected neither by cognitive impairment, sex, nor age. Perceived control mediated between BaCo but not ExCo and depressive symptoms. CONCLUSION: Future research needs to follow the connection between residents' everyday competence and their depressive symptoms longitudinally to better understand the underlying mechanisms. PMID- 27683021 TI - Intervention for Diabetes with Education, Advancement and Support (IDEAS) study: protocol for a cluster randomised controlled trial. AB - BACKGROUND: The high market penetration of mobile phones has triggered an opportunity to combine mobile technology with health care to overcome challenges in today's health care setting. Although Malaysia has a high Internet and mobile penetration rate, evaluations of the efficacy of incorporating this technology in diabetes care is not common. We report the development of a telemonitoring coaching system, using the United Kingdom (UK) Medical Research Council (MRC) framework, for patients with type 2 diabetes mellitus. METHODS: The Intervention for Diabetes with Education, Technological Advancement and Support (IDEAS) study is a telemonitoring programme based on an empowerment philosophy to enable participants to be responsible for their own health decision and behaviour. An iterative cycle of development, piloting, and collating qualitative and quantitative data will be used to inform and refine the intervention. To increase compliance, the intervention will be designed to encourage self-management using simple, non-technical knowledge. The primary outcomes will be HbA1c, blood pressure, total cholesterol, and quality of life and diabetes self-efficacy. In addition, an economic analysis on health service utilisation will be collected. DISCUSSION: The mixed-method approach in this study will allow for a holistic overview of using telemonitoring in diabetes care. This design enables researchers to understand the effectiveness of telemonitoring as well as provide insights towards the receptiveness of incorporating information technology amongst type 2 diabetes patients in a community setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02466880 Registered 2 June 2015. PMID- 27683022 TI - Screening mammography: sparing the emperor's blushes. AB - Differing interpretations about evidence on benefits and harms of screening mammography has led to conflicting recommendations among different jurisdictions that range from intensive screening starting at age 40 to no screening at all. Despite broad attention of scientific and nonscientific media, evidence suggests substantial discrepancy between real and perceived benefits of screening mammography among women. In this commentary, underlying concept of mammographic screening, limitations in primary evidence, results from secondary evidence, and existing misunderstandings are underscored with a critical gaze at available information. PMID- 27683023 TI - Impact of hospital volume on risk-adjusted mortality following oesophagectomy in Japan. AB - BACKGROUND: Previous studies have reported that patients undergoing oesophagectomy in high-volume hospitals experience lower mortality rates. However, there has been ongoing discussion regarding the validity of evidence for this association. The purpose of this study was to investigate the relationship between hospital volume and risk-adjusted mortality following oesophagectomy in Japan, using a nationwide web-based database. METHODS: The study included patients registered in the database as having undergone oesophagectomy with reconstruction between 2011 and 2013. Outcome measures were 30-day and operative mortality rates. Logistic regression analysis was used to adjust for hospital volume, surgeon volume and risk factors for mortality after oesophagectomy. RESULTS: A total of 16 556 oesophagectomies at 988 hospitals were included; the overall unadjusted 30-day and operative mortality rates were 1.1 and 3.0 per cent respectively. The unadjusted operative mortality rate in hospitals performing fewer than ten procedures per year (5.1 per cent) was more than three times higher than that in hospitals conducting 30 or more procedures annually (1.5 per cent). Multivariable models indicated that hospital volume had a significant effect on 30-day (odds ratio 0.88 per 10-patient increase; P = 0.012) and operative (odds ratio 0.86 per 10-patient increase; P < 0.001) mortality. CONCLUSION: In Japan, high-volume hospitals had lower risk-adjusted 30-day and operative mortality rates following oesophagectomy compared with low-volume hospitals. PMID- 27683024 TI - Accumulation of Metals in Juvenile Carp (Cyprinus carpio) Exposed to Sublethal Levels of Iron and Manganese: Survival, Body Weight and Tissue. AB - Many oxbows are contaminated by Fe and Mn as a consequence of the elemental concentration of sediment and water originating from the Upper Tisza Region of Hungary. The phenomenon is partly caused by anthropogenic activities and mainly due to the geochemical characteristics of the region. The effects of Fe and Mn on the aquatic ecosystem of these wetlands were investigated in a model experiments in this study. Survival, individual body weight and the elemental concentrations of organs were determined in common carp (Cyprinus carpio) juveniles reared in Fe and Mn contaminated media (treatment 1: Fe 0.57 mg L-1, Mn 0.29 mg L-1, treatment 2: Fe 0.57 mg L-1, Mn 0.625 mg L-1, treatment 3: Fe 1.50 mg L-1, Mn 0.29 mg L-1, treatment 4: Fe 1.50 mg L-1, Mn 0.625 mg L-1 and control: Fe 0.005 mg L-1, Mn 0.003 mg L-1), for rearing time of 49 days. The treatment with Fe and Mn did not have any effect on the survival data and individual body weight in the levels tested. The highest concentration of Fe and Mn was found in the liver and brain of carp juveniles, while the lowest concentration of these elements occurred in the muscular tissue and gills. The treatment where Fe and Mn were applied in the highest concentrations resulted in a statistically higher level of these elements in the brain, grills and muscle tissues. The treatment where only Mn was present in the highest concentration caused increased level of Mn only in the liver. We found metal accumulation in almost every organ; however, the applied concentrations and exposure time did not affect the survival and average body weight of carp juveniles. PMID- 27683025 TI - Control of seizures by ketogenic diet-induced modulation of metabolic pathways. AB - Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy. PMID- 27683027 TI - Mobile real-time surveillance of Zika virus in Brazil. AB - The World Health Organization has declared Zika virus an international public health emergency. Knowledge of Zika virus genomic epidemiology is currently limited due to challenges in obtaining and processing samples for sequencing. The ZiBRA project is a United Kingdom-Brazil collaboration that aims to improve this situation using new sequencing technologies. PMID- 27683026 TI - [Childhood absence epilepsy: An update]. AB - Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome accounting for 10% of all pediatric epilepsies. The aim of this review is to provide an updated overview of this epilepsy syndrome to pediatricians. Most of the patients can be initially managed in private practice or in general pediatric settings. Absence seizures are the only seizure type observed at the time of diagnosis in these patients. An electroencephalogram recording and a clinical evaluation lead to the diagnosis. The underlying mechanisms are not yet fully understood. CAE is considered a self-limited epilepsy syndrome since most of the patients will become seizure free. Only a few patients (5-10%) have resistant CAE. However, CAE, as well as any pediatric epilepsy syndrome, should not be considered a "benign" epilepsy. Attention deficit is observed in about one third of the patients. There is also an increased risk of academic difficulties related to specific cognitive disorders. Therefore, the early detection of children at risk of developing neuropsychological problems can be helpful for preventing school underachievement and poor psychosocial outcome. Recently, several studies including a large randomized controlled trial indicated that ethosuximide should be considered as a first-line treatment and valproate as a second-line treatment. Cognitive side effects should be an important factor in the selection of the antiepileptic drug and should be specifically assessed during the follow-up. This review concludes by discussing the criteria that might lead to referring the patient to a specialist. PMID- 27683028 TI - Disseminated lung cancer presenting as a rectal mass. AB - Primary lung cancer is the leading cause of cancer-related deaths globally, and approximately 50% had metastatic disease at the time of diagnosis. A rectal mass and unintended weight loss are common manifestations of rectal cancer. Our case presented with a rectal mass, but workup revealed a metastatic lesion from lung cancer. Lung cancer metastases to the lower gastrointestinal tract imply reduced survival compared with the already poor mean survival of stage IV lung cancer. Despite relevant therapy, the patient died 5 months after referral. PMID- 27683029 TI - Transplantation of mature adipocyte-derived dedifferentiated fat cells for the treatment of vesicoureteral reflux in a rat model. AB - PURPOSE: Autologous cells potentially provide an ideal injectable substance for management in vesicoureteral reflux (VUR). The aim of this study is to examine the effects of mature adipocyte-derived dedifferentiated fat (DFAT) cell transplantation on VUR in a rat bladder pressurization-induced VUR model. METHODS: To create VUR, Sprague-Dawley rats underwent urethral clamping and placement of cystostomy followed by intravesical pressurization. Rat DFAT cells (1 * 106 cells, DFAT group, n = 5) or saline (control group, n = 5) was then injected into the bilateral vesicoureteral junctions. Two weeks later, VUR grade was evaluated on cystography. The number of apoptotic cells in the renal pelvic urothelium, the ureteral inner/outer diameter ratio and the area of connective tissue in the posterior bladder wall were measured. RESULTS: The reflux grade in the DFAT group was significantly lower than that in the control group. The number of apoptotic cells in the renal pelvic urothelium, ureteral inner/outer diameter ratio and connective tissue area in DFAT group were significantly lower in comparison with the control group. CONCLUSIONS: DFAT cell transplantation improved VUR and exerted nephroprotective effects in a rat VUR model. PMID- 27683030 TI - MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-beta pathway via targeting SMAD3. AB - MicroRNAs (miRNAs) are non-coding RNAs with functions of posttranscriptional regulation. The abnormally expressed miRNAs have been shown to be crucial contributors and may serve as biomarkers in many diseases. However, determining the biological function of miRNAs is an ongoing challenge. By combining miRNA targets prediction, miRNA and mRNA expression profiles in TCGA cancers, and pathway data, we performed a miRNA-pathway regulation inference by Fisher's exact test for enrichment analysis. Then we constructed a database to show the cancer related miRNA-pathway regulatory network (http://bioinfo.life.hust.edu.cn/miR_path). As one of the miRNAs targeting many cancer related pathways, miR-142-5p potentially regulates the maximum number of genes in TGF-beta signaling pathway. We experimentally confirmed that miR-142-5p directly targeted and suppressed SMAD3, a key component in TGF-beta signaling. Ectopic overexpression of miR-142-5p significantly promoted tumor cell proliferation and inhibited apoptosis, while silencing of miR-142-5p inhibited the tumor cell proliferation and promoted apoptosis in vitro. These findings indicate that miR-142-5p plays as a negative regulator in TGF-beta pathway by targeting SMAD3 and suppresses TGF-beta-induced growth inhibition in cancer cells. Our study proved the feasibility of miRNA regulatory pathway analysis and shed light on combining bioinformatics with experiments in the research of complex diseases. PMID- 27683033 TI - A novel co-drug of aspirin and ursolic acid interrupts adhesion, invasion and migration of cancer cells to vascular endothelium via regulating EMT and EGFR mediated signaling pathways: multiple targets for cancer metastasis prevention and treatment. AB - Metastasis currently remains the predominant cause of breast carcinoma treatment failure. The effective targeting of metastasis-related-pathways in cancer holds promise for a new generation of therapeutics. In this study, we developed an novel Asp-UA conjugate, which was composed of classical "old drug" aspirin and low toxicity natural product ursolic acid for targeting breast cancer metastasis. Our results showed that Asp-UA could attenuate the adhesion, migration and invasion of breast cancer MCF-7 and MDA-MB-231 cells in a more safe and effective manner in vitro. Molecular and cellular study demonstrated that Asp-UA significantly down-regulated the expression of cell adhesion and invasion molecules including integrin alpha6beta1, CD44 ,MMP-2, MMP-9, COX-2, EGFR and ERK proteins, and up-regulated the epithelial markers "E-cadherin" and "beta catenin", and PTEN proteins. Furthermore, Asp-UA (80 mg/kg) reduced lung metastasis in a 4T1 murine breast cancer metastasis model more efficiently, which was associated with a decrease in the expression of CD44. More importantly, we did not detect side effects with Asp-UA in mice such as weight loss and main viscera tissues toxicity. Overall, our research suggested that co-drug Asp-UA possessed potential metastasis chemoprevention abilities via influencing EMT and EGFR-mediated pathways and could be a more promising drug candidate for the prevention and/or treatment of breast cancer metastasis. PMID- 27683031 TI - The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis. AB - PURPOSE: To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. RESULTS: Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and 21% (95% CI: 16%-27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%-28%), 11% (95% CI: 8%-14%) and 20% (95% CI: 11%-32%) respectively. Tumor PD-L1 expression and patient smoking status might serve as biomarkers to predict response of anti-PD-1/PD-L1 antibody treatment. Compared to tumors with negative PD-L1 expression, tumors with positive PD-L1 expression had a significantly higher clinical response rate (41.4% versus 26.5%) with RR = 1.92 (95% CI: 1.53-2.41, P < 0.001). Smoker patients also showed a significantly higher response rate (33.7%) than patients who never smoked (4.2%) with RR = 6.02 (95% CI: 1.22-29.75, P = 0.028). Nivolumab and Pembrolizumab were associated with significantly increased response rate (RR = 2.89, 95% CI: 2.46-3.40, P < 0.001), reduced death risk (HR= 0.53; 95% CI: 0.48 0.57; P < 0.001), and decreased adverse effect rate (RR = 0.49, 95% CI: 0.30 0.80, P = 0.004) compared with other therapies. EXPERIMENTAL DESIGN: Clinical trials reporting response or safety of anti-PD-1/PD-L1 antibodies for advanced or refractory cancer patients published before January 31th 2016 were searched in PubMed and EMBASE database. Meta-analyses using random effects models were used to calculate the overall estimate. CONCLUSIONS: Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers. PMID- 27683034 TI - Intraglomerular crosstalk elaborately regulates podocyte injury and repair in diabetic patients: insights from a 3D multiscale modeling study. AB - Podocytes are mainly involved in the regulation of glomerular filtration rate (GFR) under physiological condition. Podocyte depletion is a crucial pathological alteration in diabetic nephropathy (DN) and results in a broad spectrum of clinical syndromes such as protein urine and renal insufficiency. Recent studies indicate that depleted podocytes can be regenerated via differentiation of the parietal epithelial cells (PECs), which serve as the local progenitors of podocytes. However, the podocyte regeneration process is regulated by a complicated mechanism of cell-cell interactions and cytokine stimulations, which has been studied in a piecemeal manner rather than systematically. To address this gap, we developed a high-resolution multi-scale multi-agent mathematical model in 3D, mimicking the in situ glomerulus anatomical structure and micro environment, to simulate the podocyte regeneration process under various cytokine perturbations in healthy and diabetic conditions. Our model showed that, treatment with pigment epithelium derived factor (PEDF) or insulin-like growth factor-1 (IGF-1) alone merely ameliorated the glomerulus injury, while co treatment with both cytokines replenished the damaged podocyte population gradually. In addition, our model suggested that continuous administration of PEDF instead of a bolus injection sustained the regeneration process of podocytes. Part of the results has been validated by our in vivo experiments. These results indicated that amelioration of the glomerular stress by PEDF and promotion of PEC differentiation by IGF-1 are equivalently critical for podocyte regeneration. Our 3D multi-scale model represents a powerful tool for understanding the signaling regulation and guiding the design of cytokine therapies in promoting podocyte regeneration. PMID- 27683032 TI - The role of SH3GL3 in myeloma cell migration/invasion, stemness and chemo resistance. AB - Multiple myeloma (MM) is an incurable cancer characterized by clonal expansion of malignant plasma cells in the bone marrow and their egress into peripheral blood. The mechanisms of myeloma cells migration/invasion have remained unclear. Herein, we found SH3GL3 was highly expressed in the CD138-negative (CD138-) myeloma cells. The migration/invasion capability of CD138- cells was significantly higher than that in the CD138-positive (CD138+) cells. Silencing SH3GL3 using shRNA reduced myeloma cells migration/invasion. Conversely, overexpression of SH3GL3 increased myeloma cells migration/invasion. Moreover, SH3GL3 is also associated with the stemness and chemo-resistance of CD138- myeloma cells. Elevated expression of stem cell and multi-drug resistant markers were seen in the myeloma cells with overexpressed SH3GL3; while knocking-down SH3GL3 reduced the expression of these markers. A marked increase in p-PI3K and p-FAK was observed in the cells with overexpressed SH3GL3. To test if FAK/PI3K signaling pathway was involved in the SH3GL3-mediated myeloma cells migration, the cells transfected w/wo SH3GL3 cDNA were treated with FAK inhibitor 14 and PI3K inhibitor LY294002. Inhibition of FAK and PI3K attenuated SH3GL3-mediated migration /invasion. Our findings indicate that SH3GL3 plays an important role in myeloma cell migration/invasion, stemness and chemo-resistance. The SH3GL3-mediated myeloma cell migration/invasion is mediated by FAK/PI3K signaling pathway. PMID- 27683035 TI - Perturbed hematopoietic stem and progenitor cell hierarchy in myelodysplastic syndromes patients with monosomy 7 as the sole cytogenetic abnormality. AB - The stem and progenitor cell compartments in low- and intermediate-risk myelodysplastic syndromes (MDS) have recently been described, and shown to be highly conserved when compared to those in acute myeloid leukemia (AML). Much less is known about the characteristics of the hematopoietic hierarchy of subgroups of MDS with a high risk of transforming to AML. Immunophenotypic analysis of immature stem and progenitor cell compartments from patients with an isolated loss of the entire chromosome 7 (isolated -7), an independent high-risk genetic event in MDS, showed expansion and dominance of the malignant -7 clone in the granulocyte and macrophage progenitors (GMP), and other CD45RA+ progenitor compartments, and a significant reduction of the LIN-CD34+CD38low/-CD90+CD45RA- hematopoietic stem cell (HSC) compartment, highly reminiscent of what is typically seen in AML, and distinct from low-risk MDS. Established functional in vitro and in vivo stem cell assays showed a poor readout for -7 MDS patients irrespective of marrow blast counts. Moreover, while the -7 clone dominated at all stages of GM differentiation, the -7 clone had a competitive disadvantage in erythroid differentiation. In azacitidine-treated -7 MDS patients with a clinical response, the decreased clonal involvement in mononuclear bone marrow cells was not accompanied by a parallel reduced clonal involvement in the dominant CD45RA+ progenitor populations, suggesting a selective azacitidine-resistance of these distinct -7 progenitor compartments. Our data demonstrate, in a subgroup of high risk MDS with monosomy 7, that the perturbed stem and progenitor cell compartments resemble more that of AML than low-risk MDS. PMID- 27683036 TI - Proteomic analysis uncovers common effects of IFN-gamma and IL-27 on the HLA class I antigen presentation machinery in human cancer cells. AB - IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-gamma, induces the expression of IL-18BP, IDO and PD L1 immune regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN-gamma display a broad overlap of functions on human ovarian cancer cells. Indeed, among 990 proteins modulated by either cytokine treatment in SKOV3 cells, 814 showed a concordant modulation by both cytokines, while a smaller number (176) were differentially modulated. The most up-regulated proteins were common to both IFN-gamma and IL-27. In addition, functional analysis of IL-27-regulated protein networks highlighted pathways of interferon signaling and regulation, antigen presentation, protection from natural killer cell-mediated cytotoxicity, regulation of protein polyubiquitination and proteasome, aminoacid catabolism and regulation of viral protein levels.Importantly, we found that IL-27 induced HLA class I molecule expression in human cancer cells of different histotypes, including tumor cells showing very low expression. IL-27 failed only in a cancer cell line bearing a homozygous deletion in the B2M gene. Altogether, these data point out to a broad set of activities shared by IL-27 and IFN-gamma, which are dependent on the common activation of the STAT1 pathway. These data add further explanation to the anti tumor activity of IL-27 and also to its dual role in immune regulation. PMID- 27683037 TI - Interaction of microtubules with the actin cytoskeleton via cross-talk of EB1 containing +TIPs and gamma-actin in epithelial cells. AB - Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cell cell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system. LSM, 3D-SIM, proximity ligation assay (PLA) and co-immunoprecipitation methods applied in combination with selective depletion of beta- or gamma-cytoplasmic actins revealed a selective interaction between microtubules and gamma-, but not beta-cytoplasmic actin via the microtubule +TIPs protein EB1. EB1-positive comet distribution analysis and quantification have shown more effective microtubule growth in the absence of beta-actin. Our data represent the first demonstration that microtubule +TIPs protein EB1 interacts mainly with gamma-cytoplasmic actin in epithelial cells. PMID- 27683038 TI - Regulation of tumor growth by circulating full-length chromogranin A. AB - Chromogranin A (CgA), a neuroendocrine secretory protein, and its fragments are present in variable amounts in the blood of normal subjects and cancer patients. We investigated whether circulating CgA has a regulatory function in tumor biology and progression. Systemic administration of full-length CgA, but not of fragments lacking the C-terminal region, could reduce tumor growth in murine models of fibrosarcoma, mammary adenocarcinoma, Lewis lung carcinoma, and primary and metastatic melanoma, with U-shaped dose-response curves. Tumor growth inhibition was associated with reduction of microvessel density and blood flow in neoplastic tissues. Neutralization of endogenous CgA with antibodies against its C-terminal region (residues 410-439) promoted tumor growth. Structure-function studies showed that the C-terminal region of CgA contains a bioactive site and that cleavage of this region causes a marked loss of anti-angiogenic and anti tumor potency. Mechanistic studies showed that full-length CgA could induce, with a U-shaped dose-response curve, the production of protease nexin-1 in endothelial cells, a serine protease inhibitor endowed of anti-angiogenic activity. Gene silencing or neutralization of protease nexin-1 with specific antibodies abolished both anti-angiogenic and anti-tumor effects of CgA. These results suggest that circulating full-length CgA is an important inhibitor of angiogenesis and tumor growth, and that cleavage of its C-terminal region markedly reduces its activity. Pathophysiological changes in CgA blood levels and/or its fragmentation might regulate disease progression in cancer patients. PMID- 27683039 TI - Clonal and microclonal mutational heterogeneity in high hyperdiploid acute lymphoblastic leukemia. AB - High hyperdiploidy (HD), the most common cytogenetic subtype of B-cell acute lymphoblastic leukemia (B-ALL), is largely curable but significant treatment related morbidity warrants investigating the biology and identifying novel drug targets. Targeted deep-sequencing of 538 cancer-relevant genes was performed in 57 HD-ALL patients lacking overt KRAS and NRAS hotspot mutations and lacking common B-ALL deletions to enrich for discovery of novel driver genes. One-third of patients harbored damaging mutations in epigenetic regulatory genes, including the putative novel driver DOT1L (n=4). Receptor tyrosine kinase (RTK)/Ras/MAPK signaling pathway mutations were found in two-thirds of patients, including novel mutations in ROS1, which mediates phosphorylation of the PTPN11-encoded protein SHP2. Mutations in FLT3 significantly co-occurred with DOT1L (p=0.04), suggesting functional cooperation in leukemogenesis. We detected an extraordinary level of tumor heterogeneity, with microclonal (mutant allele fraction <0.10) KRAS, NRAS, FLT3, and/or PTPN11 hotspot mutations evident in 31/57 (54.4%) patients. Multiple KRAS and NRAS codon 12 and 13 microclonal mutations significantly co-occurred within tumor samples (p=4.8x10-4), suggesting ongoing formation of and selection for Ras-activating mutations. Future work is required to investigate whether tumor microheterogeneity impacts clinical outcome and to elucidate the functional consequences of epigenetic dysregulation in HD-ALL, potentially leading to novel therapeutic approaches. PMID- 27683040 TI - Perioperative treatments for resected upper tract urothelial carcinoma: a network meta-analysis. AB - BACKGROUND: Perioperative treatments have been used to improve prognosis in patients with upper tract urothelial carcinoma (UTUC). However, optimal management remains unestablished. METHODS: We searched the Embase, Web of Science and Cochrane databases for studies published before June 20, 2015. All included studies were categorised into three groups on the basis of the outcome reported (overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS)). Relative hazard ratios (HRs) for death were calculated using random-effects Bayesian network meta-analysis methods. We also ranked the three different treatments in terms of three outcomes. RESULTS: A total of 31 trials with 8100 patients were included. Compared with the control, adjuvant chemotherapy (AC) could improve OS, DSS and RFS by 32% (HR 0.68, 95% CI 0.51 0.89), 29% (HR 0.71, 95% CI 0.54-0.89) and 51% (HR 0.49, 95% CI 0.23-0.85), respectively. We noted a marked prolongation of RFS in both intravesical chemotherapy (HR 0.32, 95% CI 0.09-0.69) as well as concurrent radiotherapy and intravesical chemotherapy (HR 0.32, 95% CI 0.03-0.97) than in the control. Neoadjuvant chemotherapy (NAC) showed a significant improvement in DSS relative to the control (HR 0.25, 95% CI 0.06-0.61) and a distinct advantage over AC (HR 0.36, 95% CI 0.08-0.90) or AR (HR 6.89, 95% CI 1.25-18.66). CONCLUSIONS: Our results showed that AC; intravesical chemotherapy; and concurrent radiotherapy and intravesical chemotherapy could improve the prognosis of UTUC patients. NAC was found to be more favourable for UTUC than AC in terms of DSS. PMID- 27683042 TI - Identification of miR-30b-3p and miR-30d-5p as direct regulators of androgen receptor signaling in prostate cancer by complementary functional microRNA library screening. AB - The Androgen Receptor (AR) plays a key role in prostate biology and in the progression of prostate cancer (PCa) to castration resistance. The role of microRNAs (miRNAs) in aberrant AR signaling have not been fully characterized. Here we screened a library of 810 miRNA mimics to identify miRNAs that alter AR activity in complementary functional assays including protein lysate microarray (LMA) quantification of AR and PSA protein levels, AR transcriptional reporter activity, and AR-positive PCa cell viability. Candidate AR-regulating miRNAs were verified through AR transcriptional reporter and cell viability assays. MiRNA binding sites were found within the AR 3'-untranslated region (UTR) and within the AR and AR-V7 coding regions. MiRNA activity was characterized by western blotting, 3'-UTR reporter assay, and AR-GFP and AR-V7-GFP reporter assays. Results uncovered miR-30 family members as direct AR inhibitors. Inhibition of endogenous miR-30b-3p and miR-30d-5p enhanced AR expression and androgen independent cell growth. Droplet digital RT-PCR quantification of miR-30c-5p and miR-30d-5p revealed significantly reduced levels in metastatic castration resistant PCa (CRPC), when compared to healthy prostate tissues. MiR-30d-5p levels were inversely correlated with AR activity, as measured by PSA mRNA, in metastatic CRPC. Collectively, these studies provide a comprehensive evaluation of AR-regulating miRNAs in PCa. PMID- 27683041 TI - Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. AB - Prostate cancer can be targeted by ligands to the prostate-specific membrane antigen (PSMA). We aimed to evaluate dosimetry, safety and efficacy of 177Lu-PSMA 617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).Fifteen patients each received two cycles of 3.7 GBq (n = 5) or 6.0 GBq (n = 10) 177Lu-PSMA-617 at an eight to ten weeks interval. For safety monitoring, each treatment was followed by dosimetry with serial quantitative SPECT as well as inpatient and outpatient recording of adverse events. Response to RLT was primarily determined by baseline to follow-up change in 68Ga-PSMA PET/CT (RECIST1.1), as well as change in prostate-specific antigen (PSA), quality of life (QoL, FACT-P scale), and pain (Brief Pain Inventory) as secondary endpoints.Radiation dose delivered to the tumor (6.1 Gy/GBq) was six to twelve-fold higher than to critical organs (kidney left/right 0.5/0.6 Gy/GBq each, salivary glands 1.0 Gy/GBq). Total radiation dose per kidney did not exceed 23 Gy in any patient. Three patients had sub-acute and latent grade 3 events, i.e. anemia, leukocytopenia, and nausea. No acute events, grade >=4 events or high grade events for salivary gland or kidney function were observed. After two RLT cycles, 4 (27%) patients had partial response, 6 (40%) had stable disease, and 5 (33%) had progressive disease according to RECIST. Any PSA decline was observed in 12/15 (80%) patients during RLT. Significant pain relief was documented in 7/10 (70%) symptomatic patients and QoL improved in 9/15 (60%) patients.177Lu-PSMA-617 therapy proved safe and indicated promising response rates for both objective and patient-reported outcomes in our small group of mCRPC patients. PMID- 27683044 TI - Blockade of C5 in Severe Acute Postinfectious Glomerulonephritis Associated With Anti-Factor H Autoantibody. AB - Activation of the complement cascade plays an important role in the pathogenesis of postinfectious glomerulonephritis. We report successful terminal complement pathway blockade using an anti-C5 monoclonal antibody (eculizumab) in an 8-year old child with severe acute postinfectious glomerulonephritis requiring hemodialysis. The child presented with clinical, serologic, and histopathologic criteria for diffuse crescentic postinfectious glomerulonephritis. Complement measurements showed low C3 and C4 levels, with increased SC5b-9 titers. The presence of a transient anti-factor H autoantibody was also identified. Eculizumab (600mg, 2 doses at a 1-week interval) was administered, with a striking recovery of kidney function. There were no additional hemodialysis sessions needed after the first dose of eculizumab, and glomerular filtration rate measured using inulin clearance at 12 months of follow-up was within the normal range (92mL/min/1.73m2). Prompt terminal complement blockade may have improved the outcome in this case of severe acute postinfectious glomerulonephritis. PMID- 27683045 TI - MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report. AB - Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT TL1 gene, which encodes the mitochondrial tRNALeu(UUR). Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney. PMID- 27683043 TI - Low-dose green tea intake reduces incidence of atrial fibrillation in a Chinese population. AB - The aim of the present study was to assessthe association between green tea intake and incidence of atrial fibrillation (AF) in a Chinese population. A total of 801 (mean age: 62 years; 56% male) subjects were enrolled: 401 AF patients and 400 controls. All subjects completed a questionnaire and the associations between their green tea drinking habits and incidence of AF were assessed using the odds ratio (OR) and binary logistic regression. After multivariate adjustment, green tea intake presented as a protective factor against the incidence of AF (OR: 0.349, 95% CI: 0.253-0.483, P < 0.001). The green tea protection showed downward trend with increasing green tea intake (P for the trend= 0.001). Low frequency, low concentration, short-term tea consumption was classified as low-dose green tea intake. Green tea intake decreased the incidence of both paroxysmal AF (OR: 0.307, 95% CI: 0.216-0.436, P < 0.001) and persistent AF (OR: 0.355, 95% CI: 0.261-0.482, P < 0.001) and may be associated with a decreased incidence of AF. This study suggests that low-dose green tea intake strongly protects against AF. PMID- 27683046 TI - Stereoselective Pharmacodynamics and Pharmacokinetics of Proton Pump Inhibitors. AB - BACKGROUND: Proton pump inhibitors (PPIs) are a group of gastric acid suppressing drugs, they work by irreversibly blocking the H+/K+ ATPase. The structure of PPIs is similar. They all have a similar core with a sulphur atom chiral center combined with different substituent groups. In relation to the sulphur atom chiral center, the pharmacodynamics, pharmacokinetics are diverse between the racemates and their stereoisomers. But there are no reviews outlining the stereoselective pharmacodynamics and pharmacokinetics in PPIs. This review aims to compare the differences between the stereoisomers of PPIs in their pharmacodynamics and pharmacokinetics parameters. And exploring the development directions of PPIs at present. METHODS: We undertook a search of PubMed databases for PPI research literature including reviews, clinical studies, letters and books, in recent 20 years. The citied papers were high quality, which were carefully screened by authors using standard tools. The data of the pharmacodynamics and pharmacokinetics parameters were selected from the retrieved papers, then making generalization and summary. RESULTS: Ninety-three papers were included in the review, mainly from East Asia, America and Europe. All these papers involved the reviews of PPIs, the pharmacodynamics studies of PPIs and the pharmacokinetics studies of PPIs. Finally, omeprazole, lansoprazole, pantoprazole, rebeprazole and pantoprazole with their enantiomers were discussed in this paper. CONCLUSION: The findings of this review confirm the differences of pharmacodynamics and pharmacokinetics in the racemates and the stereoisomer of PPIs. Providing longer duration, faster time of onset and better nocturnal gastric acid secretion control are the development directions of new generation PPIs. But, due to debate on the necessity and superiority of these new drugs, more validation studies are needed. PMID- 27683048 TI - [Infection-induced rheumatic diseases]. PMID- 27683049 TI - A multidisciplinary response to commercial sexual exploitation of children. AB - Commercial sexual exploitation of children (CSEC) is associated with child abuse, neglect, poverty, homelessness, and societal causes. Sex trafficking is the participation in commercial sex acts in which force, fraud, or coercion occur. This article discusses the scope of CSEC and sex trafficking, and the necessary identification skills and medical evaluations needed to help these patients. PMID- 27683047 TI - Elevated NLR in gallbladder cancer and cholangiocarcinoma - making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium. AB - BACKGROUND: Gallbladder and extrahepatic biliary malignancies are aggressive tumors with high risk of recurrence and death. We hypothesize that elevated preoperative Neutrophil-Lymphocyte Ratios (NLR) are associated with poor prognosis among patients undergoing resection of gallbladder or extrahepatic biliary cancers. METHODS: Patients who underwent complete surgical resection between 2000-2014 were identified from 10 academic centers (n=525). Overall (OS) and recurrence-free survival (RFS) were analyzed by stratifying patients with normal (<5) versus elevated (>5) NLR. RESULTS: Overall, 375 patients had NLR <5 while 150 patients had NLR >5. Median OS was 24.5 months among patients with NLR<5 versus 17.0 months among patients with NLR>5 (p<0.001). NLR was also associated with OS in subgroup analysis of patients with gallbladder cancer. In fact, on multivariable analysis, NLR>5, dyspnea and preoperative peak bilirubin were independently associated with OS in patients with gallbladder cancer. Median RFS was 26.8 months in patients with NLR<5 versus 22.7 months among patients with NLR>5 (p=0.030). NLR>5 was independently associated with worse RFS for patients with gallbladder cancer. CONCLUSIONS: Elevated NLR was associated with worse outcomes in patients with gallbladder and extrahepatic biliary cancers after curative-intent resection. NLR is easily measured and may provide important prognostic information. PMID- 27683050 TI - Genome-wide transcriptome profiling of black poplar (Populus nigra L.) under boron toxicity revealed candidate genes responsible in boron uptake, transport and detoxification. AB - Boron (B) is an essential nutrient for normal growth of plants. Despite its low abundance in soils, it could be highly toxic to plants in especially arid and semi-arid environments. Poplars are known to be tolerant species to B toxicity and accumulation. However, physiological and gene regulation responses of these trees to B toxicity have not been investigated yet. Here, B accumulation and tolerance level of black poplar clones were firstly tested in the current study. Rooted cutting of these clones were treated with elevated B toxicity to select the most B accumulator and tolerant genotype. Then we carried out a microarray based transcriptome experiment on the leaves and roots of this genotype to find out transcriptional networks, genes and molecular mechanisms behind B toxicity tolerance. The results of the study indicated that black poplar is quite suitable for phytoremediation of B pollution. It could resist 15 ppm soil B content and >1500 ppm B accumulation in leaves, which are highly toxic concentrations for almost all agricultural plants. Transcriptomics results of study revealed totally 1625 and 1419 altered probe sets under 15 ppm B toxicity in leaf and root tissues, respectively. The highest induction were recorded for the probes sets annotated to tyrosine aminotransferase, ATP binding cassette transporters, glutathione S transferases and metallochaperone proteins. Strong up regulation of these genes attributed to internal excretion of B into the cell vacuole and existence of B detoxification processes in black poplar. Many other candidate genes functional in signalling, gene regulation, antioxidation, B uptake and transport processes were also identified in this hyper B accumulator plant for the first time with the current study. PMID- 27683051 TI - Re: Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel to treat synchronous peritoneal carcinomatosis from gastric cancer: Results from a Chinese center, Eur J Surg Oncol (2016). PMID- 27683053 TI - Integrin-linked kinase regulates cadherin switch in bladder cancer. AB - Cadherin switch is specific of epithelial-mesenchymal transition (EMT) and is closely related to tumor cell invasion. However, the molecular mechanism that promotes the phenotypic changes remains unclear and elusive. We found that integrin-linked kinase (ILK) is a key factor involved in cadherin switch. The expression and activity of ILK are elevated in a variety of cancers but its mechanisms are not exactly understood. In this report, we studied the role and mechanism of ILK in EMT of human bladder cancer. We showed that silencing of ILK expression by small interfering RNA (siRNA) significantly abolished the nuclear translocation or the presence of markers associated with EMT like Snail, Twist, Zeb, and beta-catenin. ILK knockdown by siRNA suppressed N-cadherin expression and increased re-expression of E-cadherin in bladder cancer cells. We suggest that ILK is a major signaling factor involved in EMT. It is essential to understand the molecular mechanism of EMT in aim to possibly use it in search for new therapeutic targets. PMID- 27683054 TI - High mucin-7 expression is an independent predictor of adverse clinical outcomes in patients with clear-cell renal cell carcinoma. AB - Mucin-7 is a member of the secreted mucins family. Mucins might play a crucial role during tumor development and its aberrant expression was observed in several types of tumor. Our study aims to evaluate the prognostic significance of Mucin-7 expression in postoperative clear-cell renal cell carcinoma (ccRCC) patients. In this retrospective study, we enrolled 392 patients with ccRCC undergoing nephrectomy between 2008 and 2009 in a single center. The median follow-up was 73 months (range 39-74 months). Mucin-7 expression was evaluated by immunohistochemistry protocol on ccRCC specimens. Kaplan-Meier survival analysis was conducted to compare survival curves. Univariate and multivariate Cox regression models were applied to assess the impact of prognostic factors in overall survival (OS) and recurrence-free survival (RFS). A nomogram was then constructed based on the independent prognosticators identified on multivariate analysis. The results displayed that Mucin-7 expression was significantly associated with tumor size (p = 0.034), pT stage (p = 0.004), TNM stage (p = 0.008), and necrosis (p = 0.043). Patients with high Mucin-7 expression had significant worse outcomes in both OS (p < 0.001) and RFS (p < 0.001) compared to those with low Mucin-7 expression. MUC7 expression was considered as an independent predictive factor for OS (HR 2.286; 95 %CI 1.167-4.475; p = 0.016) and RFS (HR 2.055; 95 %CI 1.086-3.887; p = 0.027). A nomogram integrating Mucin-7 expression and other independent prognosticators was constructed. In summary, the high Mucin-7 expression is a potential prognosticator of adverse clinical outcome in ccRCC patients after surgery. PMID- 27683055 TI - The anticancer effects of Resina Draconis extract on cholangiocarcinoma. AB - Cholangiocarcinoma (CCA) is a relatively rare, heterogeneous malignant tumor with poor clinical outcomes. Because of high insensitivity to chemotherapy and radiotherapy, there are no effective treatment options. Efforts to identify and develop new agents for prevention and treatment of this deadly disease are urgent. Here, we assessed the apoptotic cytotoxicity of Resina Draconis extract (RDE) using in vitro and in vivo assays and identified the mechanisms underlying antitumor effects of RDE. RDE was obtained via vacuum distillation of Resina Draconis with 75 % ethanol. The ethanol extract could inhibit CCA cell proliferation and trigger apoptotic cell death in both QBC939 and HCCC9810 cell lines in a time- and concentration-dependent manner. RDE treatment resulted in intracellular caspase-8 and poly (ADP-ribose) polymerase protease activation. RDE significantly downregulated antiapoptotic protein survivin expression and upregulated proapoptotic protein Bak expression. RDE also inhibited CCA tumor growth in vivo. We observed that human CCA tissues had much higher survivin expression than did paired adjacent normal tissue. Taken together, the current data suggested that RDE has anticancer effects on CCA, and that RDE could function as a novel anticancer agent to benefit patients with CCA. PMID- 27683052 TI - Direct targeting of HGF by miR-16 regulates proliferation and migration in gastric cancer. AB - MicroRNAs (miRNAs) have been reported to be involved in each stage of tumor development in various types of cancers. We have previously showed that miR-16 is downregulated in cancer and acts as a tumor suppressor. Other studies indicated that hepatocyte growth factor (HGF)/c-Met is implicated in proliferation, migration, and other pathophysiological processes. However, little is known about the relationship between miR-16 and HGF/c-Met in gastric cancer (GC). In the present study, we used bioinformatics tools and related experiments to search for miRNAs targeting HGF. Here, we found that miR-16 suppressed HGF protein expression by directly targeting 3'-untranslated region (UTR) of HGF mRNA. Subsequently, it was illustrated the downregulation of miR-16 promotes, while overexpressed of miR-16 significantly inhibits cell proliferation and migration by negatively regulating HGF/c-Met pathway. Moreover, the biological role of HGF in GC cells was determined by using HGF siRNA and HGF-overexpressing plasmid, respectively. To conclude, our results provide a potential target by using miR-16 for the future clinical treatment of GC. PMID- 27683058 TI - Near-membrane electric field calcium ion dehydration. AB - The dehydration of ion-water complexes prior to ion channel transit has focused on channel protein-mediated dissociation of water. Ion dehydration by the membrane electric field has not previously been considered. Near membrane electric fields have previously been shown to cause the disassociation of non covalently bound small molecule-small molecule, small molecule-protein, and protein-protein complexes. It is well known that cosmotropic, structure making ions such as calcium and sodium significantly bind multiple water ions in solution. It is also known that these ions are often not hydrated as they pass through membrane ion channels. Using capillary electrophoresis, the range of electric fields needed to strip water molecules from calcium ions has been measured. Ion migration velocity is a linear function of the electric field. At low electric fields, the migration rate of calcium ion was shown to be linearly related to the applied electric field. Using a form of the Stoke's equation applicable to ion migration, the hydrated calcium radius was found to be 0.334nm, corresponding to a water hydration shell of 5.09 water molecules. At higher electric fields, the slope of the calcium migration velocity as a function of the electric field increased, which was modeled as a decrease in the radius of the migrating ion as the water was removed. Using a tanh function to model the transition of the ion from a hydrated to a stripped state, the transition had a midpoint at 446V/cm, and was 88% complete at 587V/cm with a correlation coefficient of 0.9996. The migration velocity of the stripped calcium ion was found to be a function of both the decrease in radius and an increase in the effective, electronic viscosity of the dipole medium through which the dehydrated ion moved. The size of the electric field needed to dehydrate calcium occurs 6 7nm from the cell membrane. Calcium ions within this distance from the membrane will be devoid of water molecules when they reach the calcium selective channel pore entrances, all known to be approximately 1-2nm from the membrane. No matter what the calcium pore structure, calcium ions reaching the channel entrance will be devoid of a water shell. PMID- 27683057 TI - MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1. AB - Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence, it is imperative to determine reliable biomarkers of lung cancer prognosis. MicroRNA-490-3p has been previously reported to be a positive prognostic biomarker for hepatocellular cancer. However, its role in human lung cancer has not yet been elucidated. Here, we report that hsa-miR-490-3p expression is significantly higher in human lung cancer tissue specimens and cell line. Gain- and loss-of-function studies of hsa-miR-490-3p showed that it regulates cell proliferation and is required for induction of in vitro migration and invasion the latter being a hallmark of epithelial to mesenchymal transition. In situ analysis revealed that hsa-miR-490-3p targets poly r(C)-binding protein 1 (PCBP1), which has been previously shown to be a negative regulator of lung cancer metastasis. Reporter assays confirmed PCBP1 as a bona fide target of miR 490-3p, and metagenomic analysis revealed an inverse relation between expression of miR-490-3p and PCBP1 in metastatic lung cancer patients. In fact, PCBP1 expression, as detected by immunohistochemistry, was undetectable in advanced stages of lung cancer patients' brain and lymph node tissues. Xenograft tail vein colonization assays proved that high expression of miR-490-3p is a prerequisite for metastatic progression of lung cancer. Our results suggest that hsa-miR-490 3p might be a potential biomarker for lung cancer prognosis. In addition, we can also conclude that the lung cancer cells have evolved refractory mechanisms to downregulate the expression of the metastatic inhibitor, PCBP1. PMID- 27683056 TI - Upregulation of miR-192 inhibits cell growth and invasion and induces cell apoptosis by targeting TCF7 in human osteosarcoma. AB - MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes and are involved in multiple processes in cancer development and progression. For example, miR-192 is dysregulated in multiple human cancers, including osteosarcoma (OS). However, the pathophysiological role of miR-192 and its relevance to OS cell growth and invasion has not yet been clarified. This study aimed to investigate the expression of miR-192 in OS and elucidate the molecular mechanisms by which miR-192 acts as a tumor suppressor in this disease. The qRT PCR data identified significant down-regulation of miR-192 in 20 OS tissue samples and two OS cell lines when compared with adjacent normal tissues and a human osteoblast cell line, respectively. Furthermore, Western blot analysis revealed overexpression of T cell-specific transcription factor (TCF) 7 protein in tumor tissues compared with matched adjacent normal tissues. Further in vitro studies demonstrated that enforced expression of miR-192 inhibited U2OS and MG63 cell proliferation, invasion, and migration and induced apoptosis. Finally, Western blot and Luciferase assays identified TCF7 as a target of miR-192. Collectively, these findings suggest an important role for miR-192 in regulating the proliferation, migration, invasion, and apoptosis of OS cells through the regulation of TCF7. PMID- 27683059 TI - Evaluating Patient Usability of an Image-Based Mobile Health Platform for Postoperative Wound Monitoring. AB - BACKGROUND: Surgical patients are increasingly using mobile health (mHealth) platforms to monitor recovery and communicate with their providers in the postdischarge period. Despite widespread enthusiasm for mHealth, few studies evaluate the usability or user experience of these platforms. OBJECTIVE: Our objectives were to (1) develop a novel image-based smartphone app for postdischarge surgical wound monitoring, and (2) rigorously user test it with a representative population of vascular and general surgery patients. METHODS: A total of 9 vascular and general surgery inpatients undertook usability testing of an internally developed smartphone app that allows patients to take digital images of their wound and answer a survey about their recovery. We followed the International Organization for Standardization (ISO) 9241-11 guidelines, focusing on effectiveness, efficiency, and user satisfaction. An accompanying training module was developed by applying tenets of adult learning. Sessions were audio recorded, and the smartphone screen was mirrored onto a study computer. Digital image quality was evaluated by a physician panel to determine usefulness for clinical decision making. RESULTS: The mean length of time spent was 4.7 (2.1 12.8) minutes on the training session and 5.0 (1.4-16.6) minutes on app completion. 55.5% (5/9) of patients were able to complete the app independently with the most difficulty experienced in taking digital images of surgical wounds. Novice patients who were older, obese, or had groin wounds had the most difficulty. 81.8% of images were sufficient for diagnostic purposes. User satisfaction was high, with an average usability score of 83.3 out of 100. CONCLUSION: Surgical patients can learn to use a smartphone app for postoperative wound monitoring with high user satisfaction. We identified design features and training approaches that can facilitate ease of use. This protocol illustrates an important, often overlooked, aspect of mHealth development to improve surgical care. PMID- 27683060 TI - Quantification of the Latent HIV-1 Reservoir Using Ultra Deep Sequencing and Primer ID in a Viral Outgrowth Assay. AB - BACKGROUND: In this study, we measured the latent HIV-1 reservoir harboring replication-competent HIV-1 in resting CD4 T cells in participants on highly active antiretroviral therapy, quantitating the frequency of latent infection through the use of a Primer ID-based Ultra Deep Sequencing Assay (UDSA), in comparison to the readout of the quantitative viral outgrowth assay (QVOA). METHODS: Viral RNA derived from culture wells of QVOA that scored as HIV-1 p24 capsid antigen positive were tagged with a specific barcode during cDNA synthesis, and the sequences within the V1-V3 region of the HIV-1 env gene were analyzed for diversity using the Primer ID-based paired-end MiSeq platform. We analyzed samples from a total of 19 participants, 2 initially treated with highly active antiretroviral therapy in acute infection and 17 treated during chronic infection. Phylogenetic trees were generated with all viral lineages detected from culture wells derived from each participant to determine the number of distinct viral lineages growing out in each well, thus capturing another level of information beyond the well being positive for viral antigen. The infectious units per million (IUPM) cell values estimated using a maximum likelihood approach, based on the number of distinct viral lineages detected (VOA-UDSA), were compared with those obtained from QVOA measured using limiting dilution. RESULTS: IUPM estimates determined by VOA-UDSA ranged from 0.14 to 3.66 and strongly correlated with the IUPM estimates determined by QVOA (r = 0.94; P < 0.0001). CONCLUSIONS: VOA-UDSA may be an alternative readout for that currently used for QVOA. PMID- 27683061 TI - Persistent iatrogenic atrial septal defects after pulmonary vein isolation: long term follow-up with contrast transesophageal echocardiography. AB - PURPOSE: Pulmonary vein isolation using cryoballoon ablation is an established approach to treating atrial fibrillation. The procedure involves insertion of a 15-Fr sheath into the left atrium across the interatrial septum. This creates an iatrogenic atrial septal defect, which may have important long-term clinical relevance, especially in younger patients. We sought to determine the long-term incidence of these defects and determine the direction of shunt using contrast transesophageal echocardiography. METHODS: Individuals who had undergone a single pulmonary vein isolation procedure were invited to attend for transesophageal echocardiography (TOE). Patients who had undergone more than one procedure involving puncture of the interatrial septum were excluded. The interatrial septum was interrogated using two-dimensional imaging, color flow Doppler, and microbubble contrast study. RESULTS: A total of 27 patients were recruited with a median follow-up time of 553 days from pulmonary vein isolation to TOE. Seven patients had persistent iatrogenic atrial septal defects with three demonstrating right to left shunt either at rest or with Valsalva. There were no reported adverse events during the study period. CONCLUSIONS: Persistent iatrogenic atrial septal defects are relatively common following cryoballoon ablation procedures. Right to left shunting can be observed using microbubble contrast in a subset of patients with iatrogenic atrial septal defect (iASD). Further studies that longitudinally assess shunt fraction, pulmonary artery pressure, and the incidence of paradoxical embolism are needed to better understand the clinical impacts of such defects. PMID- 27683063 TI - Psychometric properties of the Revised Fibromyalgia Impact Questionnaire (FIQR) - a contribution to the Portuguese validation of the scale. AB - BACKGROUND: Fibromyalgia (FM) remains a relatively misunderstood and clinically challenging condition that impact significantly in the individual's life, impairing global functioning and diminishing quality of life. Management is complex and frequently unsatisfactory, requiring personal tailoring and adaptation of interventions according to the fluctuations of the disease manifestations and their response to therapy. The use of comprehensive and quantified assessment tools constitutes, therefore, an essential component of the management of patients with FM. The Revised Fibromyalgia Impact Questionnaire (FIQR) is currently one of the most used and well validated instruments to assess functional (in)capacity and global impact of FM and associated symptoms. OBJECTIVES: To translate to Portuguese the FIQR and to study its psychometric properties. MATERIAL AND METHODS: The total sample comprised 103 women with fibromyalgia, defined according to the established criteria for FM. A self-report battery composed by the Revised Fibromyalgia Impact Questionnaire (FIQR), the Portuguese version of Beck Depression Inventory-II (BDI-II) and the Profile of Mood States (PoMS) was administered. The FIQR was re-administered to twenty-four participants, six weeks after the first evaluation. Internal reliability was assessed through Cronbach's alpha, corrected item-total score correlations and alpha if item deleted. Spearman and Pearson correlations along with repeated measures tests were computed to assess the temporal stability of the scale. Convergent and divergent validity were assessed via Spearman and Pearson correlations. RESULTS: The FIQR demonstrated a good to very good internal consistency (from alpha = 0.87 to alpha = 0.94). All items correlated to a good degree (above 0.30) to the total score and contributed significantly to the overall reliability. Moreover, FIQR presented a good temporal stability (from r = .617 to r = .886, p <= .001) and favorable convergent and discriminant validity with depressive symptoms (r > .289, p <= .01) and positive (r > -.186, p > .05) and negative affect (r > .206, p <= .05). CONCLUSIONS: The Portuguese version of the FIQR demonstrated good psychometric properties, which renders it a proper and valuable tool to be used in different settings. PMID- 27683062 TI - Efficacy and safety of the second-generation cryoballoons versus radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: a systematic review and meta-analysis. AB - PURPOSE: Currently, radiofrequency (RF) and cryoballoon are the most commonly used ablation technologies for atrial fibrillation (AF). We performed a meta analysis to assess the efficacy and safety of the second-generation cryoballoons (CB-2) compared with RF for paroxysmal atrial fibrillation (PAF) ablation. METHODS: The PubMed, Cochrane Library, and Embase databases were searched and qualified studies were identified. The primary clinical outcome was the recurrence rate of atrial tachyarrhythmia (AT), and the secondary clinical outcomes were procedure time, fluoroscopy time, and the complications that followed. RESULTS: Nine observational studies (2336 patients) with a mean follow up period ranging from 8.8 to 16.8 months were included. The CB-2 group was associated with a significantly lower recurrence rate of ATs (20.8 versus 29.8 %, p = 0.01). In subgroup analysis, compared with non-contact force sensing (NCF) catheter, using CB-2 showed significantly reduced incidence of ATs (22.0 versus 38.5 %, p < 0.00001). However, the difference became negligible in contrast with contact force sensing (CF) catheter. Moreover, the CB-2 group had a tendency to decrease procedure time (weighted mean difference -39.72 min, p = 0.0003), whereas fluoroscopy time was similar between the two groups. The total complication rate showed no statistical difference (8.8 versus 4.4 %, p = 0.08). Almost all the cases of phrenic nerve palsy occurred in the CB-2 group, whereas pericardial tamponade was seldom manifested in the CB-2 group. CONCLUSIONS: CB-2 tended to be more effective in comparison to NCF catheter and at least non inferior to CF catheter, with shorter procedure time and similar safety endpoint. PMID- 27683065 TI - All Photons Imaging Through Volumetric Scattering. AB - Imaging through thick highly scattering media (sample thickness ? mean free path) can realize broad applications in biomedical and industrial imaging as well as remote sensing. Here we propose a computational "All Photons Imaging" (API) framework that utilizes time-resolved measurement for imaging through thick volumetric scattering by using both early arrived (non-scattered) and diffused photons. As opposed to other methods which aim to lock on specific photons (coherent, ballistic, acoustically modulated, etc.), this framework aims to use all of the optical signal. Compared to conventional early photon measurements for imaging through a 15 mm tissue phantom, our method shows a two fold improvement in spatial resolution (4db increase in Peak SNR). This all optical, calibration free framework enables widefield imaging through thick turbid media, and opens new avenues in non-invasive testing, analysis, and diagnosis. PMID- 27683064 TI - PTHrP-Derived Peptides Restore Bone Mass and Strength in Diabetic Mice: Additive Effect of Mechanical Loading. AB - There is an unmet need to understand the mechanisms underlying skeletal deterioration in diabetes mellitus (DM) and to develop therapeutic approaches to treat bone fragility in diabetic patients. We demonstrate herein that mice with type 1 DM induced by streptozotocin exhibited low bone mass, inferior mechanical and material properties, increased bone resorption, decreased bone formation, increased apoptosis of osteocytes, and increased expression of the osteocyte derived bone formation inhibitor Sost/sclerostin. Further, short treatment of diabetic mice with parathyroid hormone related protein (PTHrP)-derived peptides corrected these changes to levels undistinguishable from non-diabetic mice. In addition, diabetic mice exhibited reduced bone formation in response to mechanical stimulation, which was corrected by treatment with the PTHrP peptides, and higher prevalence of apoptotic osteocytes, which was reduced by loading or by the PTHrP peptides alone and reversed by a combination of loading and PTHrP peptide treatment. In vitro experiments demonstrated that the PTHrP peptides or mechanical stimulation by fluid flow activated the survival kinases ERKs and induced nuclear translocation of the canonical Wnt signaling mediator beta catenin, and prevented the increase in osteocytic cell apoptosis induced by high glucose. Thus, PTHrP-derived peptides cross-talk with mechanical signaling pathways to reverse skeletal deterioration induced by DM in mice. These findings suggest a crucial role of osteocytes in the harmful effects of diabetes on bone and raise the possibility of targeting these cells as a novel approach to treat skeletal deterioration in diabetes. Moreover, our study suggests the potential therapeutic efficacy of combined pharmacological and mechanical stimuli to promote bone accrual and maintenance in diabetic subjects. (c) 2016 American Society for Bone and Mineral Research. PMID- 27683066 TI - Photonic Crystal Microchip Laser. AB - The microchip lasers, being very compact and efficient sources of coherent light, suffer from one serious drawback: low spatial quality of the beam strongly reducing the brightness of emitted radiation. Attempts to improve the beam quality, such as pump-beam guiding, external feedback, either strongly reduce the emission power, or drastically increase the size and complexity of the lasers. Here it is proposed that specially designed photonic crystal in the cavity of a microchip laser, can significantly improve the beam quality. Experiments show that a microchip laser, due to spatial filtering functionality of intracavity photonic crystal, improves the beam quality factor M2 reducing it by a factor of 2, and increase the brightness of radiation by a factor of 3. This comprises a new kind of laser, the "photonic crystal microchip laser", a very compact and efficient light source emitting high spatial quality high brightness radiation. PMID- 27683067 TI - Assessment of the interaction of Portland cement-based materials with blood and tissue fluids using an animal model. AB - Portland cement used in the construction industry improves its properties when wet. Since most dental materials are used in a moist environment, Portland cement has been developed for use in dentistry. The first generation material is mineral trioxide aggregate (MTA), used in surgical procedures, thus in contact with blood. The aim of this study was to compare the setting of MTA in vitro and in vivo in contact with blood by subcutaneous implantation in rats. The tissue reaction to the material was also investigated. ProRoot MTA (Dentsply) was implanted in the subcutaneous tissues of Sprague-Dawley rats in opposite flanks and left in situ for 3 months. Furthermore the material was also stored in physiological solution in vitro. At the end of the incubation time, tissue histology and material characterization were performed. Surface assessment showed the formation of calcium carbonate for both environments. The bismuth was evident in the tissues thus showing heavy element contamination of the animal specimen. The tissue histology showed a chronic inflammatory cell infiltrate associated with the MTA. MTA interacts with the host tissues and causes a chronic inflammatory reaction when implanted subcutaneously. Hydration in vivo proceeds similarly to the in vitro model with some differences particularly in the bismuth oxide leaching patterns. PMID- 27683068 TI - Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves. AB - Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea caused by trigeminal nerve damage, which leads to loss of corneal sensitivity, corneal epithelium breakdown, and poor healing. Though extremely uncommon, NK is increasingly recognized for its characteristics as a distinct and well-defined clinical entity rather than a rare complication of various diseases that can disrupt trigeminal innervation. Indeed, the defining feature of NK is loss of corneal sensitivity, and its clinical findings do not correlate with the wide range of systemic or ocular conditions that underlie trigeminal nerve damage. Despite increasing awareness of NK as a distinct condition, its management continues to be challenged by the lack of treatments that target nerve regeneration. This review focuses on the role of corneal nerves in maintaining ocular surface homeostasis, the consequences (such as alterations in neuromediators and corneal cell morphology/function) of impaired innervation, and advances in NK diagnosis and management. Novel therapeutic strategies should aim to improve corneal innervation in order support corneal renewal and healing. J. Cell. Physiol. 232: 717-724, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27683069 TI - PeptideTracker: A knowledge base for collecting and storing information on protein concentrations in biological tissues. PMID- 27683070 TI - Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds. AB - PURPOSE: To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes. METHODS: Chromatic pupillography was performed in 40 patients with advanced RP (visual acuity < 0.02 or visual field <=5 degrees , non-recordable ERGs) and 40 age-matched healthy subjects. Pupil responses to full-field red (605 nm) and blue (420 nm) stimuli of 28 lx corneal illumination were recorded and analysed for two stimulus durations (1 and 4 seconds). The perception threshold of phosphenes to transcorneal electrostimulation was ascertained and correlated to the pupil responses and visual acuity. RESULTS: Patients with RP showed significantly reduced pupil responses to red and blue stimuli compared with the controls. With red stimuli, pupillary escape could be observed; blue stimuli resulted in a well-preserved postillumination pupil response. Phosphene thresholds were significantly increased in patients with RP and correlated with the parameters of the pupil response if all subjects were considered. Within the RP group alone, this relationship was less pronounced and statistically not significant. CONCLUSIONS: Chromatic pupillography demonstrated a significant decrease in outer retinal photoreceptor responses but a persisting and disinhibited intrinsic photosensitive retinal ganglion cell function in advanced RP. These phenomena may be useful as an objective marker for the efficacy of any interventional treatment for hereditary retinal diseases as well as for the selection of suitable patients for an electronic retinal implant. PMID- 27683071 TI - Nurses', midwives' and key stakeholders' experiences and perceptions on requirements to demonstrate the maintenance of professional competence. AB - AIM: To present the qualitative findings from a study on the development of scheme(s) to give evidence of maintenance of professional competence for nurses and midwives. BACKGROUND: Key issues in maintenance of professional competence include notions of self- assessment, verification of engagement and practice hours, provision of an evidential record, the role of the employer and articulation of possible consequences for non-adherence with the requirements. Schemes to demonstrate the maintenance of professional competence have application to nurses, midwives and regulatory bodies and healthcare employers worldwide. DESIGN: A mixed methods approach was used. This included an online survey of nurses and midwives and focus groups with nurses and midwives and other key stakeholders. The qualitative data are reported in this study. METHODS: Focus groups were conducted among a purposive sample of nurses, midwives and key stakeholders from January-May 2015. A total of 13 focus groups with 91 participants contributed to the study. FINDINGS: Four major themes were identified: Definitions and Characteristics of Competence; Continuing Professional Development and Demonstrating Competence; Assessment of Competence; The Nursing and Midwifery Board of Ireland and employers as regulators and enablers of maintaining professional competence. CONCLUSION: Competence incorporates knowledge, skills, attitudes, professionalism, application of evidence and translating learning into practice. It is specific to the nurse's/midwife's role, organizational needs, patient's needs and the individual nurse's/midwife's learning needs. Competencies develop over time and change as nurses and midwives work in different practice areas. Thus, role-specific competence is linked to recent engagement in practice. PMID- 27683073 TI - Monophasic beta-TCP vs. biphasic HA/beta-TCP in two-stage sinus floor augmentation procedures - a prospective randomized clinical trial. AB - OBJECTIVES: To compare a monophasic (100% beta-TCP) and a biphasic (60% HA and 40% beta-TCP) bone substitute material (BSM) regarding biocompatibility, osteoconductivity and implant stability using histological, radiological and resonance frequency analysis. MATERIAL AND METHODS: Sixty-seven sinus floor elevations were performed in 60 patients. One patient group (monophasic bone substitute [MBS], 30 patients, 32 sinuses) was augmented by the use of the monophasic material (Bioresorb(r) , Sybron Implant Solutions, Bremen, Germany), while the second group (biphasic bone substitute (BBS), 30 patients, 35 sinuses) received a biphasic material (Maxresorb(r) , Botiss Biomaterials, Berlin, Germany). Cone beam CT images were taken immediately after augmentation and prior to implant placement after 6 months. Trephines were harvested, while the implant bed was prepared. Resonance frequency analysis was performed immediately after implant placement and 6 months later. Descriptive analysis was performed on all augmented sinus (n = 67). For statistical comparison of the groups, one sinus of each bilaterally treated patient was randomly excluded, resulting in 30 sinuses grafted with MBS and 30 sinuses grafted with BBS (n = 60). RESULTS: Histomorphometrical analysis of all sinuses displayed comparable results for both groups regarding new bone matrix (MBS 36.16 +/- 19.37%, BBS 38.42 +/- 12.61%), residual BSM (MBS 30.26 +/- 11.7%, BBS 32.66 +/- 12.57%) and non-mineralized tissue (MBS 34.29 +/- 18.32%, BBS 28.92 +/- 15.04) %) (P > 0.05, respectively). Radiological volume of BBS was significantly more stable (volume loss of 22.2% for MBS, 6.66% for BBS; P < 0.001), and homogeneity of the graft after 6 months was higher for BBS than that for MBS (P < 0.05). Resonance frequency analysis endorsed a higher implant stability quotient for BBS after 6 months than that for MBS (MBS 78.31 +/- 5.81, BBS 80.42 +/- 6.31; P < 0.05, Mann-Whitney U-test, respectively). CONCLUSION: Both monophasic and biphasic materials show good biocompatibility and osteoconductivity with satisfactory support on implant stability. BBS remains more stable in terms of volume maintenance and radiological graft homogeneity after a healing period of 6 months. PMID- 27683075 TI - Factors Affecting Communication Patterns between Oncology Staff and Family Members of Deceased Patients: A Cross-Sectional Study. AB - OBJECTIVE: Perceptions of the role of oncology medical staff in supporting bereaved families have evolved with the transition to interdisciplinary cancer care. We investigated the interactions between oncology professionals and bereaved families. METHODS: This cross-sectional study involved all oncology medical staff at the Davidoff Center. Participants were given a questionnaire relating to bereavement follow-up. Responses were measured using a 5-point Likert scale. RESULTS: Of 155 staff members, 107 filled questionnaires with <20% missing data and were included in the analysis (alpha = 0.799; corrected, alpha = 0.821). Respondents included physicians (35%), nurses (46%), social workers (7%), psychologists (4%), or unspecified (8%); 85% were Jewish, and 60% had >=10 years of oncology experience. Most respondents thought that contacting bereaved families was important (73%), and that it provided closure for staff (79%); 41% indicated that they contacted >50% of the families of their deceased patients. Contacting bereaved families was considered the responsibility of the physicians (90%), nurses (84%), or social workers (89%). The main barriers to contacting bereaved families were emotional overload (68%) and lack of time (63%); 60% indicated a need for additional communication tools for bereavement follow-up. In a multivariate analysis, profession (physician vs. nurse), primary workplace (outpatient setting vs. other), and self-defined religion were significant variables with respect to the perceived importance of contacting bereaved families and to actually contacting them. Other factors (e.g., age, gender) were non-significant. CONCLUSIONS: Perspectives regarding bereavement actions differ significantly across medical professions, work settings, and self-defined religions. Additional guidance and education regarding bereavement actions is warranted. PMID- 27683076 TI - The association between Ehlers-Danlos syndrome-hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study. AB - BACKGROUND: Patients with Ehlers-Danlos syndrome-hypermobility type (EDS-HT) have increased prevalence of gastrointestinal (GI) symptoms, particularly reflux and dyspepsia. EDS-HT is associated with dysautonomia, psychopathology, and chronic pain which can be associated with GI symptoms. The association between GI symptoms and EDS-HT in a 'non-patient' population and the effect of the above mentioned factors has never been studied. METHODS: In a cross sectional study, a hypermobility questionnaire was used to screen university students; further clinical examination established the diagnosis of EDS-HT. Validated questionnaires assessed for GI, somatic, pain and autonomic symptoms, psychopathology and quality of life (QOL). These were compared in students with and without EDS-HT; logistic regression analysis examined associations between EDS-HT, GI symptoms and other variables. KEY RESULTS: Of 1998 students screened, 162 were included: 74 EDS-HT (21.0 years, 53% female) vs 88 Non-EDS-HT (21.5 years, 65% female). Compared to non-EDS-HT students, EDS-HT students were more likely to have multiple GI symptoms (41.9% vs 27.3% P=.05), particularly postprandial fullness (34.4% vs 15.9%, P=.01) and early satiety (32% vs 17%, P=.03), greater autonomic (P<.001) and somatic symptoms (P=.04) but not psychopathology (P>.8). The association between EDS-HT and postprandial symptoms was dependent on autonomic factors but independent of pain and psychopathology. Pain-related QOL scores were reduced in the EDS-HT group (80 vs 90, P=.03). CONCLUSIONS AND INFERENCES: The previously described association between EDS-HT, dyspepsia, pain and autonomic symptoms in patients is also present in non-patient groups. Future studies are necessary to explore the etiological role of connective tissue in GI and extra intestinal symptoms. PMID- 27683074 TI - SDHA mutation with dominant transmission results in complex II deficiency with ocular, cardiac, and neurologic involvement. AB - Isolated defects of the mitochondrial respiratory complex II (succinate dehydrogenase, SDH) are rare, accounting for approximately 2% of all respiratory chain deficiency diagnoses. Here, we report clinical and molecular investigations of three family members with a heterozygous mutation in the large flavoprotein subunit SDHA previously described to cause complex II deficiency. The index patient presented with bilateral optic atrophy and ocular movement disorder, a progressive polyneuropathy, psychiatric involvement, and cardiomyopathy. Two of his children presented with cardiomyopathy and methylglutaconic aciduria in early childhood. The daughter deceased at the age of 7 months due to cardiac insufficiency. The 30-year old son presents with cardiomyopathy and developed bilateral optic atrophy in adulthood. Of the four nuclear encoded proteins composing complex II (SDHA, SDHB, SDHC, SDHD) and currently known assembly factors SDHAF1 and SDHAF2 mainly recessively inherited mutations have been described in SDHA, SDHB, SDHD, and SDHAF1 to be causative for mitochondrial disease phenotypes. This is the second report presenting autosomal dominant inheritance of a SDHA mutation.(c) 2016 Wiley Periodicals, Inc. PMID- 27683072 TI - Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies. AB - OBJECTIVE: To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016. STUDY SELECTION: Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years. METHODS: Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay. RESULTS: In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15). CONCLUSION: Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years. PMID- 27683077 TI - Highly tunable refractive index visible-light metasurface from block copolymer self-assembly. AB - The refractive index of natural transparent materials is limited to 2-3 throughout the visible wavelength range. Wider controllability of the refractive index is desired for novel optical applications such as nanoimaging and integrated photonics. We report that metamaterials consisting of period and symmetry-tunable self-assembled nanopatterns can provide a controllable refractive index medium for a broad wavelength range, including the visible region. Our approach exploits the independent control of permeability and permittivity with nanoscale objects smaller than the skin depth. The precise manipulation of the interobject distance in block copolymer nanopatterns via pattern shrinkage increased the effective refractive index up to 5.10. The effective refractive index remains above 3.0 over more than 1,000 nm wavelength bandwidth. Spatially graded and anisotropic refractive indices are also obtained with the design of transitional and rotational symmetry modification. PMID- 27683078 TI - The significance of routine biochemical markers in patients with major depressive disorder. AB - The aim of our study is to examine the levels of routine biochemical markers in patients with major depressive disorder (MDD), and combine multiple biochemical parameters to assess the discriminative power for patients with MDD. We used the Hamilton Depression (HAMD) score to evaluate the severity of depressive symptoms in 228 patients with MDD. The phase of depression severity was between moderate and severe in MDD patients. There were significant differences between MDD patients and healthy controls in alanine transaminase (ALT), urea nitrogen (UN), lactate dehydrogenase (LDH), uric acid (UA), total protein (TP), total bile acid (TBA), creatinine (Cr), total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil), high density lipoprotein-cholesterol (HDL-C), fasting blood-glucose (FBG) and fructosamine (SF). Multivariate analysis showed that UN, FBG, HDL-C, SF, TP, Cr and Tbil remained independently association with MDD. Further, a logit equation was established to identify patients with MDD. The composite markers exhibited an area under the curve of 0.810 with cut-off values of 0.410. Our results suggest the associations between UN, FBG, HDL-C, TP, Cr, Tbil, SF and MDD, use of these routine biochemical markers in combination may contribute to improve the complete management for patients with MDD. PMID- 27683079 TI - [Reduce sedentary behaviour among children - a systematic review]. AB - BACKGROUND AND OBJECTIVES: Sedentary behaviour is itself a health-related behaviour. This systematic review examines whether family-based interventions can reduce sitting time among children and adolescents and which variables moderate potential intervention effects. METHODS: Using a systematic literature search we identified family-based randomised controlled intervention studies that focus on sedentary behaviour in 3- to 18-year-old children and youth. The methodological quality of studies as well as the intervention effects according to different outcomes (screen-based vs. overall sitting) were analysed and evaluated for moderating effects. RESULTS: Of 29 studies, 17 reported significant effects and 11 studies showed positive trends for reduced sitting time. The content of interventions, the level of theoretical underpinning as well as the methodological quality of studies were heterogeneous. Most often, screen-based sitting and seldom overall sitting was examined. Concise characteristics of intervention success were not clearly apparent. The proportion of positive intervention effects was higher in reducing sitting in front of TVs compared to other outcomes. An analysis of moderators highlighted that intervention programs among pre-schoolers showed more often positive intervention effects. DISCUSSION: There are many promising opportunities to reduce sitting time using family-based approaches. Statements in terms of replication of interventions and explanations of the effective mechanisms within interventions are limited. Therefore, future interventions should use subjective as well as objective evaluation measures and consider overall sitting time. To strengthen the basis of interventional effort in this research field, a theoretical planning approach is recommended. PMID- 27683080 TI - Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection. AB - Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV) is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associated with increased RV-induced asthma exacerbation severity. We examined the contribution of T helper 1 cells to RV-induced airways inflammation using mice deficient in the transcription factor T-Box Expressed In T Cells (Tbet), a critical controller of T helper 1 cell differentiation. Using flow cytometry we showed that Tbet deficient mice lacked the T helper 1 response of wild type mice and instead developed mixed T helper 2/T helper 17 responses to RV infection, evidenced by increased numbers of GATA binding protein 3 (GATA-3) and RAR-related orphan receptor gamma t (RORgammat), and interleukin-13 and interleukin-17A expressing CD4+ T cells in the lung. Forkhead box P3 (FOXP3) and interleukin-10 expressing T cell numbers were unaffected. Tbet deficient mice also displayed deficiencies in lung Natural Killer, Natural Killer T cell and gammadeltaT cell responses, and serum neutralising antibody responses. Tbet deficient mice exhibited pronounced airways eosinophilia and mucus production in response to RV infection that, by utilising a CD4+ cell depleting antibody, were found to be T helper cell dependent. RV induction of T helper 2 and T helper 17 responses may therefore have an important role in directly driving features of allergic airways disease such as eosinophilia and mucus hypersecretion during asthma exacerbations. PMID- 27683081 TI - Modulating sphingosine 1-phosphate signaling with DOP or FTY720 alleviates vascular and immune defects in mouse sepsis. AB - Sepsis is a systemic inflammatory response to pathogens and a leading cause of hospital related mortality worldwide. Sphingosine 1-phosphate (S1P) regulates multiple cellular processes potentially involved in the pathogenesis of sepsis, including antigen presentation, lymphocyte egress, and maintenance of vascular integrity. We thus explored the impact of manipulating S1P signaling in experimental polymicrobial sepsis in mice. Administration of 4-deoxypyridoxine (DOP), an inhibitor of the S1P-degrading enzyme S1P-lyase, or of the sphingosine analog FTY720 that serves as an S1P receptor agonist after phosphorylation ameliorated morbidity, improved recovery from sepsis in surviving mice, and reduced sepsis-elicited hypothermia and body weight loss. Treated mice developed lymphopenia, leading to an accumulation of lymphocytes in peripheral lymph nodes, and reduced bacterial burden in liver, but not in blood. Sepsis-induced upregulation of mRNA expression of cytokines in spleen remained unchanged, but reduction of IL-6, TNF-alpha, MCP-1, and IL-10 in plasma was evident. DOP and FTY720 treatment significantly reduced levels of Evans blue leakage from blood into liver and lung, decreased hematocrit values, and lowered plasma levels of VEGF-A in septic mice. Collectively, our results indicate that modulation of S1P signaling showed a protective phenotype in experimental sepsis by modulating vascular and immune functions. PMID- 27683083 TI - Relaxation and contraction rates - underestimated parameters of vascular contractility? PMID- 27683082 TI - WEVOTE: Weighted Voting Taxonomic Identification Method of Microbial Sequences. AB - BACKGROUND: Metagenome shotgun sequencing presents opportunities to identify organisms that may prevent or promote disease. The analysis of sample diversity is achieved by taxonomic identification of metagenomic reads followed by generating an abundance profile. Numerous tools have been developed based on different design principles. Tools achieving high precision can lack sensitivity in some applications. Conversely, tools with high sensitivity can suffer from low precision and require long computation time. METHODS: In this paper, we present WEVOTE (WEighted VOting Taxonomic idEntification), a method that classifies metagenome shotgun sequencing DNA reads based on an ensemble of existing methods using k-mer-based, marker-based, and naive-similarity based approaches. Our evaluation on fourteen benchmarking datasets shows that WEVOTE improves the classification precision by reducing false positive annotations while preserving a high level of sensitivity. CONCLUSIONS: WEVOTE is an efficient and automated tool that combines multiple individual taxonomic identification methods to produce more precise and sensitive microbial profiles. WEVOTE is developed primarily to identify reads generated by MetaGenome Shotgun sequencing. It is expandable and has the potential to incorporate additional tools to produce a more accurate taxonomic profile. WEVOTE was implemented using C++ and shell scripting and is available at www.github.com/aametwally/WEVOTE. PMID- 27683084 TI - SPATA5 mutations cause a distinct autosomal recessive phenotype of intellectual disability, hypotonia and hearing loss. AB - We examined an extended, consanguineous family with seven individuals with severe intellectual disability and microcephaly. Further symptoms were hearing loss, vision impairment, gastrointestinal disturbances, and slow and asymmetric waves in the EEG. Linkage analysis followed by exome sequencing revealed a homozygous variant in SPATA5 (c.1822_1824del; p.Asp608del), which segregates with the phenotype in the family. Molecular modelling suggested a deleterious effect of the identified alterations on the protein function. In an unrelated family, we identified compound heterozygous variants in SPATA5 (c.[2081G > A];[989_991delCAA]; p.[Gly694Glu];[.Thr330del]) in a further individual with global developmental delay, infantile spasms, profound dystonia, and sensorineural hearing loss. Molecular modelling suggested an impairment of protein function in the presence of both variants.SPATA5 is a member of the ATPase associated with diverse activities (AAA) protein family and was very recently reported in one publication to be mutated in individuals with intellectual disability, epilepsy and hearing loss. Our results describe new, probably pathogenic variants in SPATA5 that were identified in individuals with a comparable phenotype. We thus independently confirm that bi-allelic pathogenic variants in SPATA5 cause a syndromic form of intellectual disability, and we delineate its clinical presentation. PMID- 27683085 TI - Chest closure without drainage after open patent ductus arteriosus ligation in Ugandan children: A non blinded randomized controlled trial. AB - BACKGROUND: There is clinical equipoise regarding post-operative management of patients with patent ductus arteriosus (PDA) without insertion of a chest drain. This study evaluated post operative outcomes of chest closure with or without a drain following Patent Ductus Arteriosus ligation among childen at Uganda Heart Instritute (UHI). METHODS: This was an open label randomized controlled trial of 62 children 12 years of age and below diagnosed with patent ductus arteriosus at Mulago National Teaching and Referral Hospital, Uganda. Participants were randomized in the ratio of 1:1 with surgical ligation of patent ductus arteriosus to either thoracotomy closure with a chest tube or without a chest tube. All participants received standard care and were monitored hourly for 24 hours then until hospital discharge. The combined primary endpoint consisted of significant pleural space accumulation of fluid or air, higher oxygen need or infection of the surgical site. Analysis was conducted by multivariable logistic regression analysis at 5 % significance level. RESULTS: We enrolled 62 participants, 46 (74 %) of whom were females. Their median age was 12 months (IQR: 8-36). Participants in the no-drain arm significantly had less post-operative complications compared to the drain arm (Unadjusted odds ratio [uOR]: 0.21, 95 % CI: 0.06-0.73, p = 0.015). This "protective effect" remained without statistical significance in the multivariable regression model (Adjusted odds ratio [aOR]: 0.07, 95 % CI: 0.00 2.50, p = 0.144). CONCLUSION: Children aged below 6 years with patent ductus arterious can safely and effectively have thoracotomy closure without using a drain in uncomplicated surgical ligation of the PDA. Chest drain was associated with post-operative complications. TRIAL REGISTRATION: The trial was registered in the Pan African Clinical Trials registry on 1st/July/2012, retrospectively registered. Identifier number PACTR201207000395469 . PMID- 27683086 TI - Correlates of Enhanced Sexual Pleasure from Condom Use: A Study of Young Black Men Who Have Sex with Men in the United States. AB - This study of young Black MSM (YBMSM) explored the correlates and outcomes of enhanced sexual pleasure from condom-protected sex. Six-hundred YBMSM were enrolled from an sexually transmitted infection clinic in the southern United States. Men completed a computer-assisted self-interview. A 3-item scale assessed perceptions related to condoms enhancing sexual pleasure. Nine of 14 correlates met the screening level of significance and were tested in a regression model. Three obtained multivariable significance: (1) Men discussing condom use with sex partners had greater odds (AOR = 1.67, 95 % CI 1.20-2.34) of experiencing enhanced pleasure; (2) Insertive-partners had lower odds (AOR = 0.63, 95 % CI 0.44-0.91) of experiencing enhanced pleasure; and (3) men scoring higher in internalized homophobia had lower odds (AOR = 0.66, 95 % CI 0.47-0.93) of experiencing enhanced pleasure. Also, men experiencing enhanced pleasure were less likely to report any condomless anal sex. The experience of enhanced sexual pleasure during condom-protected sex may be an important "target" of behavioral intervention efforts. PMID- 27683088 TI - Mapping Dual-Degree Programs in Social Work and Public Health: Results From a National Survey. AB - Dramatic changes in the health system due to national health reform are raising important questions regarding the educational preparation of social workers for the new health arena. While dual-degree programs in public health and social work can be an important response to what is needed educationally, little is known about them. The National MSW/MPH Programs Study surveyed MSW/MPH program administrators to better understand the prevalence, models, structure, and challenges of these dual-degree programs. Forty-two programs were identified, and 97.6% of those contacted participated (n=41). Findings indicate that MSW/MPH programs are popular, increasing, geographically dispersed, and drawing talented students interested in trans-disciplinary public health social work practice. Challenges for these programs include the need for greater institutional support, particularly funding, and a general lack of best practices for MSW/MPH education. While findings from this study suggest graduates appear especially well-prepared for leadership and practice in the new health environment, additional research is needed to assess their particular contributions and career trajectories. PMID- 27683089 TI - Symposium Introduction: Papers on 'Modeling National Health Expenditures'. AB - Significant contributions have been made since the World Health Organization published Brian Abel-Smith's pioneering comparative study of national health expenditures more than 50 years ago. There have been major advances in theories, model specifications, methodological approaches, and data structures. This introductory essay provides a historical context for this line of work, highlights four newly published studies that move health economics research forward, and indicates several important areas of challenging but potentially fruitful research to strengthen future contributions to the literature and make empirical findings more useful for evaluating health policy decisions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27683087 TI - Identity information content depends on the type of facial movement. AB - Facial movements convey information about many social cues, including identity. However, how much information about a person's identity is conveyed by different kinds of facial movements is unknown. We addressed this question using a recent motion capture and animation system, with which we animated one avatar head with facial movements of three types: (1) emotional, (2) emotional in social interaction and (3) conversational, all recorded from several actors. In a delayed match-to-sample task, observers were best at matching actor identity across conversational movements, worse with emotional movements in social interactions, and at chance level with emotional facial expressions. Model observers performing this task showed similar performance profiles, indicating that performance variation was due to differences in information content, rather than processing. Our results suggest that conversational facial movements transmit more dynamic identity information than emotional facial expressions, thus suggesting different functional roles and processing mechanisms for different types of facial motion. PMID- 27683090 TI - A population pharmacokinetic model to predict oxypurinol exposure in patients on haemodialysis. AB - PURPOSE: The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS: Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not receiving dialysis were used to develop a population pharmacokinetic model in NONMEM. Deterministic simulations were used to predict the steady-state area under the oxypurinol plasma concentration time curve over 1 week (AUC7days). RESULTS: The pharmacokinetics of oxypurinol were best described by a one-compartment model with a separate parameter for dialytic clearance. Allopurinol 100 mg daily produced an AUC7days of 279 MUmol/L h in dialysis patients, a value 50-75 % lower than the AUC7days predicted for patients with normal renal function taking 200 to 400 mg daily (427-855 MUmol/L h). Dosing pre dialysis resulted in about a 25-35 % reduction in exposure compared to post dialysis. CONCLUSIONS: Oxypurinol is efficiently removed by dialysis. The population dialytic and total (non-dialytic) clearance of oxypurinol were found to be 8.23 and 1.23 L/h, standardised to a fat-free mass of 70 kg and creatinine clearance of 6 L/h, respectively. Our results suggest that if the combination of low-dose allopurinol and haemodialysis does not result in sustained urate lowering below treatment targets (serum urate <=0.36 mmol/L), then allopurinol doses may be increased to optimise oxypurinol exposure. PMID- 27683091 TI - Linear trichilemmomas on the ankle of a 28-year-old female. AB - Trichilemmomas are benign cutaneous proliferations derived from the outer root sheath of the hair follicle. They most often occur on the head and neck region and show a female predominance. When multiple, they are associated with Cowden syndrome (CS), a rare disorder due to an autosomal dominant germline mutation in PTEN (phosphatase and tensin homolog on chromosome 10), a tumor suppressor gene. Trichilemmomas outside of the head and neck region are rare, and as such, the association with CS is not clear. A 28-year-old healthy female with no significant family history of cancer presented to her dermatologist with multiple erythematous papules on the left anterior ankle, starting at birth. A shave biopsy confirmed the diagnosis of trichilemmoma with focal desmoplastic features (or desmoplastic trichilemmoma). A PTEN immunohistochemical study showed patchy (but not complete) loss of staining of the lesional cells. After shave removal, the trichilemmomas recurred 1-2 months later. PMID- 27683093 TI - Bronchial artery aneurysm: a rare, undescribed cause of Horner syndrome. PMID- 27683094 TI - Replication stress as a source of telomere recombination during replicative senescence in Saccharomyces cerevisiae. AB - Replicative senescence is triggered by short unprotected telomeres that arise in the absence of telomerase. In addition, telomeres are known as difficult regions to replicate due to their repetitive G-rich sequence prone to secondary structures and tightly bound non-histone proteins. Here we review accumulating evidence that telomerase inactivation in yeast immediately unmasks the problems associated with replication stress at telomeres. Early after telomerase inactivation, yeast cells undergo successive rounds of stochastic DNA damages and become dependent on recombination for viability long before the bulk of telomeres are getting critically short. The switch from telomerase to recombination to repair replication stress-induced damage at telomeres creates telomere instability, which may drive further genomic alterations and prepare the ground for telomerase-independent immortalization observed in yeast survivors and in 15% of human cancer. PMID- 27683092 TI - Double overexpression of DREB and PIF transcription factors improves drought stress tolerance and cell elongation in transgenic plants. AB - Although a variety of transgenic plants that are tolerant to drought stress have been generated, many of these plants show growth retardation. To improve drought tolerance and plant growth, we applied a gene-stacking approach using two transcription factor genes: DEHYDRATION-RESPONSIVE ELEMENT-BINDING 1A (DREB1A) and rice PHYTOCHROME-INTERACTING FACTOR-LIKE 1 (OsPIL1). The overexpression of DREB1A has been reported to improve drought stress tolerance in various crops, although it also causes a severe dwarf phenotype. OsPIL1 is a rice homologue of Arabidopsis PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), and it enhances cell elongation by activating cell wall-related gene expression. We found that the OsPIL1 protein was more stable than PIF4 under light conditions in Arabidopsis protoplasts. Transactivation analyses revealed that DREB1A and OsPIL1 did not negatively affect each other's transcriptional activities. The transgenic plants overexpressing both OsPIL1 and DREB1A showed the improved drought stress tolerance similar to that of DREB1A overexpressors. Furthermore, double overexpressors showed the enhanced hypocotyl elongation and floral induction compared with the DREB1A overexpressors. Metabolome analyses indicated that compatible solutes, such as sugars and amino acids, accumulated in the double overexpressors, which was similar to the observations of the DREB1A overexpressors. Transcriptome analyses showed an increased expression of abiotic stress-inducible DREB1A downstream genes and cell elongation-related OsPIL1 downstream genes in the double overexpressors, which suggests that these two transcription factors function independently in the transgenic plants despite the trade-offs required to balance plant growth and stress tolerance. Our study provides a basis for plant genetic engineering designed to overcome growth retardation in drought-tolerant transgenic plants. PMID- 27683095 TI - Human transcription factors in yeast: the fruitful examples of P53 and NF-kB. AB - The observation that human transcription factors (TFs) can function when expressed in yeast cells has stimulated the development of various functional assays to investigate (i) the role of binding site sequences (herein referred to as response elements, REs) in transactivation specificity, (ii) the impact of polymorphic nucleotide variants on transactivation potential, (iii) the functional consequences of mutations in TFs and (iv) the impact of cofactors or small molecules. These approaches have found applications in basic as well as applied research, including the identification and the characterisation of mutant TF alleles from clinical samples. The ease of genome editing of yeast cells and the availability of regulated systems for ectopic protein expression enabled the development of quantitative reporter systems, integrated at a chosen chromosomal locus in isogenic yeast strains that differ only at the level of a specific RE targeted by a TF or for the expression of distinct TF alleles. In many cases, these assays were proven predictive of results in higher eukaryotes. The potential to work in small volume formats and the availability of yeast strains with modified chemical uptake have enhanced the scalability of these approaches. Next to well-established one-, two-, three-hybrid assays, the functional assays with non-chimeric human TFs enrich the palette of opportunities for functional characterisation. We review ~25 years of research on human sequence-specific TFs expressed in yeast, with an emphasis on the P53 and NF-kB family of proteins, highlighting outcomes, advantages, challenges and limitations of these heterologous assays. PMID- 27683096 TI - Sudden onset of parathyroid hormone-independent severe hypercalcemia from reversal of tumoral calcinosis in a dialysis patient. AB - BACKGROUND: Tumoral calcinosis is a rare manifestation of extraskeletal calcification, featuring large calcified cystic masses in the periarticular regions of large joints. In chronic kidney disease (CKD), this disorder is thought to evolve through a chronically elevated calcium-phosphorus solubility product leading to calcium precipitation in soft tissue. Treating tumoral calcinosis in these patients involves interventions to lower the calcium phosphorus product such as reduction in vitamin D therapy and intensive hemodialysis regimens. CASE PRESENTATION: We report the case of a 54-year old woman with polycystic kidney disease on peritoneal dialysis with widespread tumoral calcinosis in the context of hypercalcemic tertiary hyperparathyroidism who had been on long-term alfacalcidol therapy. After withdrawal of the vitamin D analogue and initiation of daily hemodialysis, there was rapid dissolution of her tumoral calcium deposits with the abrupt onset of parathyroid hormone (PTH) independent transient hypercalcemia that resolved once the soft tissue deposits disappeared. CONCLUSIONS: Resorption of soft tissue calcific deposits may result in transient parathyroid hormone (PTH)-independent hypercalcemia. In CKD patients, this hypercalcemia causes a decrease in the PTH level, distinguishing it from tertiary hyperparathyroidism, though PTH may not be totally suppressed, the way it is seen in PTH-independent hypercalcemia in non-CKD patients. PMID- 27683097 TI - Erratum to: Radiation Engineering of Multifunctional Nanogels. PMID- 27683098 TI - Semiconductor Quantum Dots with Photoresponsive Ligands. AB - Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer. PMID- 27683099 TI - Geraniol suppresses prostate cancer growth through down-regulation of E2F8. AB - Geraniol, an acyclic dietary monoterpene, has been found to suppress cancer survival and growth. However, the molecular mechanism underlying the antitumor action of geraniol has not been investigated at the genome-wide level. In this study, we analyzed the microarray data obtained from geraniol-treated prostate cancer cells. Geraniol potently altered a gene expression profile and primarily down-regulated cell cycle-related gene signatures, compared to linalool, another structurally similar monoterpene that induces no apparent phenotypic changes. Master regulator analysis using the prostate cancer-specific regulatory interactome identified that the transcription factor E2F8 as a specific target molecule regulates geraniol-specific cell cycle signatures. Subsequent experiments confirmed that geraniol down-regulated E2F8 expression and the knockdown of E2F8 was sufficient to suppress cell growth by inducing G2 /M arrest. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. Therefore, our study provides insight into the role of E2F8 in prostate cancer biology and therapeutics. PMID- 27683100 TI - The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results. AB - BACKGROUND: The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala. METHODS: Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Munster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy. RESULTS: From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5-year event-free survival and overall survival estimates ( +/- standard error) were 56.2% +/- 2.1% and 64.1% +/- 2.1%, respectively, with a 5-year cumulative incidence of relapse of 28.9% +/- 2.0%. Twenty-one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt-related transcription factor 1 (ETV6/RUNX1) fusion. CONCLUSIONS: A well organized center in a low-middle-income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436-448. (c) 2016 American Cancer Society. PMID- 27683102 TI - Collective synchrony increases prosociality towards non-performers and outgroup members. AB - Previous research has found that behavioural synchrony between people leads to greater prosocial tendencies towards co-performers. In this study, we investigated the scope of this prosocial effect: does it extend beyond the performance group to an extended ingroup (extended parochial prosociality) or even to other people in general (generalized prosociality)? Participants performed a simple rhythmic movement either in time (synchrony condition) or out of time (asynchrony condition) with each other. Before and during the rhythmic movement, participants were exposed to a prime that made salient an extended ingroup identity. After the task, half of the participants had the opportunity to help an extended ingroup member; the other half had the opportunity to help an outgroup member. We found a main effect of our synchrony manipulation across both help targets suggesting that the prosocial effects of synchrony extend to non performers. Furthermore, there was a significantly higher proportion of participants willing to help an outgroup member after moving collectively in synchrony. This study shows that under certain intergroup contexts synchrony can lead to generalized prosociality with performers displaying greater prosociality even towards outgroup members. PMID- 27683104 TI - Iatrogenic Menopause After Treatment for Cervical Cancer. AB - The ever-improving prognosis of women diagnosed with cervical cancer has meant that survivorship and treatment-related sequelae are being brought more into the spotlight in an attempt to try to reduce morbidity and improve women's long-term health. However, there are many issues surrounding an iatrogenic menopause in cervical cancer, a variety of potential management options and barriers to treatment. Women who have become menopausal under the age of 45 years as a result of cervical cancer are significantly less likely to start hormone replacement therapy (HRT) or continue it long term as compared with those who have undergone a surgical menopause for a benign reason. High profile media reports raising concerns about the safety of HRT use have left many women reluctant to consider HRT as a therapeutic option for menopausal symptoms and many are seeking to use complementary/alternative medicine, including non-pharmacological interventions, to alleviate symptoms. The benefits of HRT in this population have been shown to reduce these effects, although adherence to treatment regimens is a challenge due to poor compliance, which is in part due to the fear of a second malignancy. The development of non-HRT-based interventions to ameliorate menopausal symptoms and reduce the long-term health consequences are needed for women who choose not to take HRT. PMID- 27683101 TI - An Amphotericin B Derivative Equally Potent to Amphotericin B and with Increased Safety. AB - Amphotericin B is the most potent antimycotic known to date. However due to its large collateral toxicity, its use, although long standing, had been limited. Many attempts have been made to produce derivatives with reduced collateral damage. The molecular mechanism of polyene has also been closely studied for this purpose and understanding it would contribute to the development of safe derivatives. Our study examined polyene action, including chemical synthesis, electrophysiology, pharmacology, toxicology and molecular dynamics. The results were used to support a novel Amphotericin B derivative with increased selectivity: L-histidine methyl ester of Amphotericin B. We found that this derivative has the same form of action as Amphotericin B, i.e. pore formation in the cell membrane. Its reduced dimerization in solution, when compared to Amphotericin B, is at least partially responsible for its increased selectivity. Here we also present the results of preclinical tests, which show that the derivative is just as potent as Amphotericin B and has increased safety. PMID- 27683105 TI - Medicine shortages: a commentary on causes and mitigation strategies. AB - Shortages of medicines and vaccines have been reported in countries of all income levels in recent years. Shortages can result from one or multiple causes, including shortages of raw materials, manufacturing capacity problems, industry consolidation, marketing practices, and procurement and supply chain management. Existing approaches to mitigate shortages include advance notice systems managed through medicine regulatory authorities, special programmes that track medicines, and interventions to improve efficiency of the medicine supply chain. Redistribution of supplies at the national level can mitigate some shortages in the short term. International redistribution and exceptional regulatory approvals may be used in limited circumstances, with the understanding that such approaches are complex and may introduce cost and quality risks. If it is necessary to prioritise patients to receive a medicine that is in shortage, evidence-based practice should be used to ensure optimal allocation. Important steps in reducing medicine shortages and their impact include identifying medicines that are most at risk, developing reporting systems to share information on current and emerging shortages, and improving data from medicine supply chains. PMID- 27683103 TI - Population-Based External Validation of the Updated 2012 Partin Tables in Contemporary North American Prostate Cancer Patients. AB - OBJECTIVE: To externally validate the updated 2012 Partin Tables in contemporary North American patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa) at community institutions. MATERIALS AND METHODS: We examined records of 25,254 patients treated with RP and pelvic lymph node dissection (PLND) between 2010 and 2013, within the surveillance, epidemiology, and end results database. The ROC derived AUC assessed discriminant properties of the updated 2012 Partin Tables of organ confined disease (OC), extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI). Calibration plots focused on calibration between predicted and observed rates. RESULTS: Proportions of OC, ECE, SVI, and LNI at RP were 69.8%, 18.4%, 7.4%, and 4.4%, respectively. Accuracy for prediction of OC, ECE, SVI, and LNI was 70.4%, 59.9%, 72.9%, and 77.1%, respectively. In subgroup analyses in patients with nodal yield >10, accuracy for LNI prediction was 76.0%. Subgroup analyses in elderly patients and in African American patients revealed decreased accuracy for prediction of all four endpoints. Last but not least, SVI and LNI calibration plots showed excellent agreement, versus good agreement for OC (maximum underestimation of 10%) and poor agreement for ECE (maximum overestimation of 12%). CONCLUSION: Taken together, the updated 2012 Partin Tables can be unequivocally endorsed for prediction of OC, SVI, and LNI in community-based patients with localized PCa. Conversely, ECE predictions failed to reach the minimum accuracy requirements of 70%. Prostate 77:105-113, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27683106 TI - Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection. AB - As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA 1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 +/- 0.98 vs. 1.48 +/- 0.22; p=0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection. PMID- 27683107 TI - Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases. AB - Phosphodiesterase 4D7 was recently shown to be specifically over-expressed in localized prostate cancer, raising the question as to which regulatory mechanisms are involved and whether other isoforms of this gene family (PDE4D) are affected under the same conditions.We investigated PDE4D isoform composition in prostatic tissues using a total of seven independent expression datasets and also included data on DNA methylation, copy number and AR and ERG binding in PDE4D promoters to gain insight into their effect on PDE4D transcription.We show that expression of PDE4D isoforms is consistently altered in primary human prostate cancer compared to benign tissue, with PDE4D7 being up-regulated while PDE4D5 and PDE4D9 are down regulated. Disease progression is marked by an overall down-regulation of long PDE4D isoforms, while short isoforms (PDE4D1/2) appear to be relatively unaffected. While these alterations seem to be independent of copy number alterations in the PDE4D locus and driven by AR and ERG binding, we also observed increased DNA methylation in the promoter region of PDE4D5, indicating a long lasting alteration of the isoform composition in prostate cancer tissues.We propose two independent metrics that may serve as diagnostic and prognostic markers for prostate disease: (PDE4D7 - PDE4D5) provides an effective means for distinguishing PCa from normal adjacent prostate, whereas PDE4D1/2 - (PDE4D5 + PDE4D7 + PDE4D9) offers strong prognostic potential to detect aggressive forms of PCa and is associated with metastasis free survival. Overall, our findings highlight the relevance of PDE4D as prostate cancer biomarker and potential drug target. PMID- 27683108 TI - Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations. AB - The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics. PMID- 27683109 TI - Pseudoexons provide a mechanism for allele-specific expression of APC in familial adenomatous polyposis. AB - Allele-specific expression (ASE) of the Adenomatous Polyposis Coli (APC) gene occurs in up to one-third of families with adenomatous polyposis (FAP) that have screened mutation-negative by conventional techniques. To advance our understanding of the genomic basis of this phenomenon, 54 APC mutation-negative families (21 with classical FAP and 33 with attenuated FAP, AFAP) were investigated. We focused on four families with validated ASE and scrutinized these families by sequencing of the blood transcriptomes (RNA-seq) and genomes (WGS). Three families, two with classical FAP and one with AFAP, revealed deep intronic mutations associated with pseudoexons. In all three families, intronic mutations (c.646-1806T>G in intron 6, c.1408+729A>G in intron 11, and c.1408+731C>T in intron 11) created new splice donor sites resulting in the insertion of intronic sequences (of 127 bp, 83 bp, and 83 bp, respectively) in the APC transcript. The respective intronic mutations were absent in the remaining polyposis families and the general population. Premature stop of translation as the predicted consequence as well as co-segregation with polyposis supported the pathogenicity of the pseudoexons. We conclude that next generation sequencing on RNA and genomic DNA is an effective strategy to reveal and validate pseudoexons that are regularly missed by traditional screening methods and is worth considering in apparent mutation-negative polyposis families. PMID- 27683110 TI - Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells. AB - Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-alpha and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth. PMID- 27683111 TI - miR-135a promotes gastric cancer progression and resistance to oxaliplatin. AB - Resistance to oxaliplatin (OXA)-based chemotherapy regimens continues to be a major cause of gastric cancer (GC) recurrence and metastasis. We analyzed GC samples and matched non-tumorous control stomach tissues from 280 patients and found that miR-135a was overexpressed in GC samples relative to control tissues. Tumors with high miR-135a expression were more likely to have aggressive characteristics (high levels of carcino-embryonic antigen, vascular invasion, lymphatic metastasis, and poor differentiation) than those with low levels. Patients with greater tumoral expression of miR-135a had shorter overall survival times and times to disease recurrence. Furthermore, miR-135a, which promotes the proliferation and invasion of OXA-resistant GC cells, inhibited E2F transcription factor 1 (E2F1)-induced apoptosis by downregulating E2F1 and Death-associated protein kinase 2 (DAPK2) expression. Our results indicate that higher levels of miR-135a in GC are associated with shorter survival times and reduced times to disease recurrence. The mechanism whereby miR-135a promotes GC pathogenesis appears to be the suppression of E2F1 expression and Sp1/DAPK2 pathway signaling. PMID- 27683113 TI - ESM1 mediates NGFR-induced invasion and metastasis in murine oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (OSCC) is a highly invasive and metastatic malignancy. The nerve growth factor receptor (NGFR) has been observed to be expressed on a subset of cells in OSCC, and NGFR+ cells have greater tumor initiating capacity in vivo. Further, inhibition of NGFR reduces tumor growth, indicating a functional role of this receptor; however, the mechanisms by which NGFR confers enhanced tumor formation are not known. Here, we used an established murine model of OSCC and gene expression array analysis to identify ESM1 as a downstream target gene of NGFR, critical for tumor invasion and metastasis. ESM1 encodes a protein called endocan, which has the property of regulating proliferation, differentiation, migration, and adhesion of different cell types. Incubation of NGFR+ murine OSCC cells with nerve growth factor resulted in increased expression of ESM1. Importantly, ESM1 overexpression conferred an enhanced migratory, invasive, and metastatic phenotype, similar to what has been correlated with NGFR expression. Conversely, shRNA knockdown of ESM1 in NGFR overexpressing OSCC cells abrogated the tumor growth kinetics and the invasive and metastatic properties associated with NGFR. Together, our data indicate that NGFR plays an important role in the pathogenesis and progression of OSCC via regulation of ESM1. PMID- 27683112 TI - Glutathione-mediated antioxidant response and aerobic metabolism: two crucial factors involved in determining the multi-drug resistance of high-risk neuroblastoma. AB - Neuroblastoma, a paediatric malignant tumor, is initially sensitive to etoposide, a drug to which many patients develop chemoresistance. In order to investigate the molecular mechanisms responsible for etoposide chemoresistance, HTLA-230, a human MYCN-amplified neuroblastoma cell line, was chronically treated with etoposide at a concentration that in vitro mimics the clinically-used dose. The selected cells (HTLA-Chr) acquire multi-drug resistance (MDR), becoming less sensitive than parental cells to high doses of etoposide or doxorubicin. MDR is due to several mechanisms that together contribute to maintaining non-toxic levels of H2O2. In fact, HTLA-Chr cells, while having an efficient aerobic metabolism, are also characterized by an up-regulation of catalase activity and higher levels of reduced glutathione (GSH), a thiol antioxidant compound. The combination of such mechanisms contributes to prevent membrane lipoperoxidation and cell death. Treatment of HTLA-Chr cells with L-Buthionine-sulfoximine, an inhibitor of GSH biosynthesis, markedly reduces their tumorigenic potential that is instead enhanced by the exposure to N-Acetylcysteine, able to promote GSH synthesis.Collectively, these results demonstrate that GSH and GSH-related responses play a crucial role in the acquisition of MDR and suggest that GSH level monitoring is an efficient strategy to early identify the onset of drug resistance and to control the patient's response to therapy. PMID- 27683114 TI - Methylation of RAD51B, XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory signature in squamous cell carcinoma of the head and neck, lung and cervix. AB - Immune checkpoints are emerging treatment targets, but mechanisms underlying checkpoint expression are poorly understood. Since alterations in DNA repair genes have been connected to the efficacy of checkpoint inhibitors, we investigated associations between methylation of DNA repair genes and CTLA4 and CD274 (PD-L1) expression.A list of DNA repair genes (179 genes) was selected from the literature, methylation status and expression of inflammation-associated genes (The Cancer Genome Atlas data) was correlated in head and neck squamous cell carcinoma (HNSCC), cervical and lung squamous cell carcinoma.A significant positive correlation of the methylation status of 15, 3 and 2 genes with checkpoint expression was identified, respectively. RAD51B methylation was identified in all cancer subtypes. In HNSCC and cervical cancer, there was significant enrichment for homologous recombination genes. Methylation of the candidate genes was also associated with expression of other checkpoints, ligands, MHC- and T-cell associated genes as well as an interferon-inflammatory immune gene signature, predictive for the efficacy of PD-1 inhibition in HNSCC.Homologous recombination deficiency might therefore be mediated by DNA repair gene hypermethylation and linked to an immune-evasive phenotype in SCC. The methylation status of these genes could represent a new predictive biomarker for immune checkpoint inhibition. PMID- 27683115 TI - CD8+/FOXP3+ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer. AB - Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). The present study investigated the prognostic values of programmed death-ligand 1 (PD L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p < 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p < 0.001). Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC. PMID- 27683116 TI - Targeting endogenous DLK1 exerts antitumor effect on hepatocellular carcinoma through initiating cell differentiation. AB - Cancer stem cells (CSCs) are responsible for tumor initiation and progression. We previously showed that Delta-like homolog 1 (DLK1) may be a therapeutic target against the CSCs of human hepatocellular carcinoma (HCC). However, the therapeutic efficacy and underlying mechanism remain unclear. Here we demonstrated that knockdown of DLK1 using a tet-inducible short hairpin RNA (shRNA) system significantly inhibited proliferation, spheroid formation and in vivo xenograft tumor growth of human HCC cells. Furthermore, in an orthotopic xenograft mouse model, adenovirus-mediated DLK1 knockdown could significantly reduce tumor size, as shown by in vivo imaging approach. Subsequently, an adenoviral vector harboring mouse Dlk1 shRNA was applied. The results showed that Dlk1 knockdown also could inhibit tumor progression in a diethylnitrosamine (DEN) induced mouse HCC model. At cellular mechanism, DLK1 knockdown delayed the cell cycle G1-S transition, along with the decreased expression of cyclin E1 and D1. Significantly, DLK1 knockdown resulted in the decrease of molecular markers such as AFP and EpCAM for hepatic progenitor cells, but the increase of KRT18 and KRT19 for the differentiated hepatocytes. The collective data indicated that targeting endogenous DLK1 may exert antitumor effect on HCCs possibly through initiating cell differentiation. PMID- 27683117 TI - Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway. AB - OBJECTIVE: To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics. METHODS: Pathologic grade and expressions of glial fibrillary acidic protein (GFAP), Ki67 (proliferation marker), and FMRP were determined in astrocytoma specimens from 74 patients. Kaplan-Meier survival analysis was undertaken. Pathologic grade and protein levels of FMRP were determined in 24 additional patients with astrocytoma and 6 controls (cerebral trauma). In cultured U251 and U87 cell lines, the effects of FMRP knock-down on cell proliferation, AKT/mTOR/GSK-3beta and MEK/ERK signaling were studied. The effects of FMRP knock-down on the volumes and weights of U251 cell-derived orthotopic tumors in mice were investigated. RESULTS: In patients, FMRP expression was increased in grade IV (5.1-fold, P<0.01) and grade III (3.2-fold, P<0.05) astrocytoma, compared with controls. FMRP and Ki67 expressions were positively correlated (R2=0.877, P<0.001). Up-regulation of FMRP was associated with poorer survival among patients with FMRP integrated optical density >30 (P<0.01). In astrocytoma cell lines, FMRP knock-down slowed proliferation (P<0.05), inhibited total MEK levels P<0.05, and reduced phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204) (P<0.05). In mice with orthotopic tumors, FMRP knock-down decreased FMRP and Ki67 expressions, and reduced tumor volume and weight (36.3% or 61.5% on day 15, both P<0.01). Also, phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204), and total MEK in xenografts were decreased in sh-FMRP xenografts compared with non-transfected ones (all P<0.05). CONCLUSION: Enhanced FMRP expression in astrocytoma may promote proliferation through activation of MEK/ERK signaling. PMID- 27683118 TI - Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells. AB - Beclin 1 has emerged as a haploinsufficient tumor suppression gene in a variety of human carcinomas. In order to clarify the role of Beclin 1 in thyroid cancer, Beclin 1 was knockdown in thyroid cancer cell lines. The current study demonstrated that knockdown of Beclin 1 resulted in morphological and molecular changes of thyroid cancer cells consistent with epithelial-mesenchymal transition (EMT), a morphogenetic procedure during which cells lose their epithelial characteristics and acquire mesenchymal properties concomitantly with gene expression reprogramming. In addition, the current study presented evidence demonstrating that Beclin 1 knockdown triggered this prometastatic process via stabilization of the EMT inducer ZEB1 mRNA through upregulation of AU-binding factor 1 (AUF1), which is recruited to the 3'-untranslated region (UTR) of the ZEB1 mRNA and decreases its degradation. We also found a negative correlation of Beclin 1 with AUF1 or ZEB1 in thyroid cancer tissues. These results indicated that at least some tumor suppressor functions of Beclin 1 were mediated through posttranscriptional regulation of ZEB1 via AUF1 in thyroid cancers. PMID- 27683119 TI - Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models. AB - Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet. Earlier studies from our laboratory revealed that decreased tissue levels of Profilin-1 (PFN1) are correlated with BC progression to muscle invasive disease. Herein, we describe a comprehensive analysis of PFN1 silencing via shRNA, in vitro (by employing T24M cells) and in vivo [(with T24M xenografts in non-obese diabetic severe combined immunodeficient mice (NOD/SCID) mice]. A combination of phenotypic and molecular assays, including migration, proliferation, adhesion assays, flow cytometry and total mRNA sequencing, as well as immunohistochemistry for investigation of selected findings in human specimens were applied. A decrease in BC cell adhesion and tumor growth in vivo following PFN downregulation are observed, likely associated with the concomitant downregulation of Fibronectin receptor, Endothelin-1, and Actin polymerization. A decrease in the levels of multiple key members of the non canonical Wnt/Ca2+ signaling pathway is also detected following PFN1 suppression, providing the groundwork for future studies, addressing the specific role of PFN1 in Ca2+ signaling, particularly in the muscle invasive disease. PMID- 27683120 TI - Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested. AB - Abnormal methylation of certain cancer related genes strongly predicts a diagnosis of head and neck cancer (HNC), while the predictive power of methylation of other DNA markers for HNC remains unclear. To systemically assess the diagnostic value of DNA methylation patterns for HNC and the effect of methylation platform techniques and sample types, we performed a PubMed search for studies of the correlation between DNA methylation and HNC completed before July 2016, and extracted the sensitivity and specificity for methylated biomarkers. Across these studies, DNA methylation showed high sensitivity for diagnosing HNC in solid tissue (0.57), and high specificity in saliva (0.89). Area under the curve (AUC) from summary receiver operating characteristic (SROC) curves revealed that DNA methylation had more diagnostic power in solid tissue (AUC = 0.82) than saliva (AUC = 0.80) or blood (AUC = 0.77). Combinations of multiple methylated genes were more sensitive diagnostic markers than single methylated genes. Our results suggest that the diagnostic accuracy of methylated biomarkers for HNC varied by sample type and were most accurate when results from multiple sample types were considered. PMID- 27683121 TI - Long non-coding RNAs LOC285194, RP11-462C24.1 and Nbla12061 in serum provide a new approach for distinguishing patients with colorectal cancer from healthy controls. AB - Colorectal cancer (CRC) is currently the most prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for CRC screening. Accumulating evidence reveals that long non-coding RNAs (lncRNAs) detectable in serum are associated with the genesis and development of various types of cancer. Therefore, we examined the diagnostic ability of lncRNAs in blood samples from patients with CRC by evaluating the levels of 17 CRC- or gastrointestinal cancer related lncRNAs in serum samples from 71 CRC patients and 70 healthy individuals using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We detected 13 lncRNAs in serum, three of which displayed significantly different levels between CRC patients and healthy controls. A three-lncRNA signature (LOC285194, RP11-462C24.1 and Nbla12061) identified via stepwise regression analysis showed potential as a diagnostic marker for CRC. The area under the receiver operating characteristic curve of this signature for distinguishing CRC patients from healthy individuals was 0.793 (95% CI: 0.709 to 0.861). The diagnostic ability of this marker was much higher than that of conventional blood biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125) and carbohydrate antigen 724 (CA724). Combining this novel marker with conventional biomarkers produced even greater diagnostic ability. Furthermore, the levels of the three lncRNAs decreased after the patients underwent surgical resection. The results of this study suggest an additional marker for CRC screening and provide new directions for further investigation. PMID- 27683122 TI - Different growth and metastatic phenotypes associated with a cell-intrinsic change of Met in metastatic melanoma. AB - A dynamic phenotypic change contributes to the metastatic progression and drug resistance in malignant melanoma. Nevertheless, mechanisms for a phenotypic change have remained to be addressed. Here, we show that Met receptor expression changes in a cell-autonomous manner and can distinguish phenotypical differences in growth, as well as in metastatic and drug-resistant characteristics. In metastatic melanoma, the cells are composed of Met-low and Met-high populations. Met-low populations have stem-like gene expression profiles, are resistant to chemotherapeutic agents, and have shown abundant angiogenesis and rapid tumor growth in subcutaneous inoculation. Met-high populations have a differentiated phenotype, are relatively resistant to B-RAF inhibitor, and are highly metastatic to the lungs. Met plays a definitive role in lung metastasis because the lung metastasis of Met-high cells requires Met, and treatment of mice with the Met containing exosomes from Met-high cells facilitates lung metastasis by Met-low cells. Clonal cell fate analysis showed the hierarchical phenotypical changes from Met-low to Met-high populations. Met-low cells either showed self-renewal or changed into Met-high cells, whereas Met-high cells remained Met-high. Clonal transition from Met-low to Met-high cells accompanied changes in the gene expression profile, in tumor growth, and in metastasis that were similar to those in Met-high cells. These findings indicate that malignant melanoma has the ability to undergo phenotypic change by a cell-intrinsic/autonomous mechanism that can be characterized by Met expression. PMID- 27683124 TI - Development of a selected reaction monitoring mass spectrometry-based assay to detect asparaginyl endopeptidase activity in biological fluids. AB - Cancer Biomarkers have the capability to improve patient outcomes. They have potential applications in diagnosis, prognosis, monitoring of disease progression and measuring response to treatment. This type of information is particularly useful in the individualisation of treatment regimens. Biomarkers may take many forms but considerable effort has been made to identify and quantify proteins in biological fluids. However, a major challenge in measuring protein in biological fluids, such as plasma, is the sensitivity of the assay and the complex matrix of proteins present. Furthermore, determining the effect of proteases in disease requires measurement of their activity in biological fluids as quantification of the protein itself may not provide sufficient information. To date little progress has been made towards monitoring activity of proteases in plasma. The protease asparaginyl endopeptidase has been implicated in diseases such as breast cancer, leukaemia and dementia. Here we describe a new approach to sensitively and in a targeted fashion quantify asparaginyl endopeptidase activity in plasma using a synthetic substrate peptide protected from nonspecific hydrolysis using D amino acids within the structure. Our selected reaction monitoring approach enabled asparaginyl endopeptidase activity to be measured in human plasma with both a high dynamic range and sensitivity. This manuscript describes a paradigm for future development of assays to measure protease activities in biological fluids as biomarkers of disease. PMID- 27683123 TI - The changing 50% inhibitory concentration (IC50) of cisplatin: a pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemoresistance in ovarian cancer. AB - Inconsistencies in the half-maximal (50%) inhibitory concentration (IC50) data for anticancer chemotherapeutic agents have yielded irreproducible experimental results and thus reciprocally contradictory theories in modern cancer research. The MTT assay is currently the most extensively used method for IC50 measurements. Here, we dissected the critical reasons behind MTT-dependent IC50 inconsistencies. We showed that IC50 errors caused by the technical deficiencies of the MTT assay are large and not adjustable (range: 300-11,000%). To overcome severe MTT artifacts, we developed an unbiased direct IC50 measurement method, the limiting dilution assay. This detection technique led us to the discovery of the inherent density-dependent chemoresistance variation of cancer cells, which is manifold and unpredictable in its forms. The subsequent intracellular signaling pathway analysis indicated that pAkt and p62 expression levels correlated with alterations in the IC50 values for cisplatin in ovarian cancer, providing an explainable mechanism for this property. An in situ pAkt-and-p62 based immunohistochemical (IHCpAkt+p62) scoring system was thereby established. Both the limiting dilution assay and the IHCpAkt+p62 scoring system accurately predicted the primary chemoresistance against cisplatin in ovarian cancer patients. Furthermore, two distinct chemoresistant recurrence patterns were uncovered using these novel detection tools, which were linked to two different forms of density-chemoresistance relationships (positively vs. negatively correlated), respectively. An interpretation was given based on the cancer evolution theory. We concluded that the density-related IC50 uncertainty is a natural property of the cancer cells and that the precise measurement of the density-dependent IC50 spectrum can benefit both basic and clinical cancer research fields. PMID- 27683125 TI - Reduced argininosuccinate synthetase expression in refractory sarcomas: Impacts on therapeutic potential and drug resistance. AB - BACKGROUND: Treating drug-resistant sarcomas remains a major challenge. The present study aimed to identify a novel therapy for drug-resistant sarcomas based on metabolic errors involving argininosuccinate synthetase1 (ASS1). RESULTS: ASS1 expression was reduced in Dox-resistant sarcoma cells. Immunohistochemistry and real-time PCR showed an inverse correlation between ASS1 and P-gp expressions. The inhibition of cellular proliferation with G1-arrest was shown to lead to autophagy with arginine deprivation. In addition, the combination of an autophagy inhibitor plus arginine deprivation was more effective than arginine deprivation alone. In cells with suppressed ASS1 expression, P-gp expression was upregulated as compared to that in negative controls. DISCUSSION: These results indicate that the reduced ASS1 expression in Dox-resistant sarcomas may contribute to drug resistance in association with the expression of P-gp. ASS1 deficiency is a potential target for novel drug therapies. The combination of arginine deprivation therapy and an autophagy inhibitor may have anti-tumor effects in refractory sarcomas. METHODS: We assessed the expressions of ASS1 and P glycoprotein (P-gp) in clinical specimens and cell lines of osteosarcoma (KHOS), doxorubicin (Dox)-resistant osteosarcoma (KHOSR2), epithelioid sarcomas (ES-X and VAESBJ) and alveolar soft part sarcoma (ASPS-KY). Each cell line was cultured in arginine-containing and arginine-free media. Cell growth was assessed using an XTT assay and flow cytometry. We analyzed the induction of autophagy in arginine free medium. Moreover, we assessed the expression of P-gp after suppressing ASS1 in Dox-sensitive cells (MCF-7 and KHOS) and after transfecting ASS1 into Dox resistant cells (ES-X, VAESBJ, ASPS-KY and KHOSR2). PMID- 27683126 TI - Hydroxychloroquine potentiates carfilzomib toxicity towards myeloma cells. AB - Cells degrade proteins either by proteasomes that clinically are targeted by for example bortezomib or carfilzomib, or by formation of autophagosomes and lysosomal degradation that can be inhibited by hydroxychloroquine (HCQ). Multiple myeloma is unique among cancers because proteasomal inhibition has good clinical effects. However, some multiple myeloma patients display intrinsic resistance to the treatment and most patients acquire resistance over time. We hypothesized that simultaneous targeting both arms of protein degradation could be a way to improve treatment of multiple myeloma. Here we tested the combined effects of the lysosomal inhibitor HCQ and clinically relevant proteasome inhibitors on myeloma cell lines and primary cells. Carfilzomib and bortezomib both induced immunoglobulin-containing aggregates in myeloma cells. HCQ significantly potentiated the effect of carfilzomib in both cell lines and in primary myeloma cells. In contrast, HCQ had little or no effects on the toxicity of bortezomib. Furthermore, cells adapted to tolerate high levels of carfilzomib could be re sensitized to the drug by co-treatment with HCQ. Thus, we show that inhibition of lysosomal degradation can overcome carfilzomib resistance, suggesting that the role of autophagy in myeloma cells is dependent on type of proteasome inhibitor. In conclusion, attempts should be made to combine HCQ with carfilzomib in the treatment of multiple myeloma. PMID- 27683127 TI - High-efficacy targeting of colon-cancer liver metastasis with Salmonella typhimurium A1-R via intra-portal-vein injection in orthotopic nude-mouse models. AB - Liver metastasis is the main cause of colon cancer-related death and is a recalcitrant disease. We report here the efficacy and safety of intra-portal-vein (iPV) targeting of Salmonella typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. Nude mice with HT29 human colon cancer cells, expressing red fluorescent protein (RFP) (HT29-RFP), growing in the liver were administered S. typhimurium A1-R by either iPV (1*104 colony forming units (CFU)/100 MUl) or, for comparison, intra-venous injection (iv; 5*107 CFU/100 MUl). Similar amounts of bacteria were delivered to the liver with the two doses, indicating that iPV delivery is 5*103 times more efficient than iv delivery. Treatment efficacy was evaluated by tumor fluorescent area (mm2) and total fluorescence intensity. Tumor fluorescent area and fluorescence intensity highly correlated (p<0.0001). iPV treatment was more effective compared to both untreated control and iv treatment (p<0.01 and p<0.05, respectively with iPV treatment with S. typhimurium arresting metastatic growth). There were no significant differences in body weight between all groups. The results of this study suggest that S. typhimurium A1-R administered iPV has potential for peri operative adjuvant treatment of colon cancer liver metastasis. PMID- 27683130 TI - Foreword: Seminars in Research 2014 Joint Experiences in Rheumatology and Dermatology. PMID- 27683129 TI - Nebulized C1-Esterase Inhibitor does not Reduce Pulmonary Complement Activation in Rats with Severe Streptococcus Pneumoniae Pneumonia. AB - Complement activation plays an important role in the pathogenesis of pneumonia. We hypothesized that inhibition of the complement system in the lungs by repeated treatment with nebulized plasma-derived human C1-esterase inhibitor reduces pulmonary complement activation and subsequently attenuates lung injury and lung inflammation. This was investigated in a rat model of severe Streptococcus pneumoniae pneumonia. Rats were intra-tracheally challenged with S. pneumoniae to induce pneumonia. Nebulized C1-esterase inhibitor or saline (control animals) was repeatedly administered to rats, 30 min before induction of pneumonia and every 6 h thereafter. Rats were sacrificed 20 or 40 h after inoculation with bacteria. Brochoalveolar lavage fluid and lung tissue were obtained for measuring levels of complement activation (C4b/c), lung injury and inflammation. Induction of pneumonia was associated with pulmonary complement activation (C4b/c at 20 h 1.24 % [0.56-2.59] and at 40 h 2.08 % [0.98-5.12], compared to 0.50 % [0.07-0.59] and 0.03 % [0.03-0.03] in the healthy control animals). The functional fraction of C1 INH was detectable in BALF, but no effect was found on pulmonary complement activation (C4b/c at 20 h 0.73 % [0.16-1.93] and at 40 h 2.38 % [0.54-4.19]). Twenty hours after inoculation, nebulized C1-esterase inhibitor treatment reduced total histology score, but this effect was no longer seen at 40 h. Nebulized C1 esterase inhibitor did not affect other markers of lung injury or lung inflammation. In this negative experimental animal study, severe S. pneumoniae pneumonia in rats is associated with pulmonary complement activation. Repeated treatment with nebulized C1-esterase inhibitor, although successfully delivered to the lungs, does not affect pulmonary complement activation, lung inflammation or lung injury. PMID- 27683131 TI - The effect of etanercept on vascular endothelial growth factor production by cutaneous mesenchymal stem cells from patients with psoriasis. AB - OBJECTIVE: To evaluate prospectively the effect of etanercept (a tumour necrosis factor [TNF]-alpha inhibitor) on vascular endothelial growth factor (VEGF) production by mesenchymal stem cells (MSC) from patients with psoriasis. METHODS: MSCs from lesional and perilesional skin were isolated, cultured and characterized. VEGF production was evaluated at baseline and after 12 weeks' etanercept treatment. RESULTS: Etanercept treatment resulted in significant reductions in VEGF production compared with baseline in both lesional MSCs (256.42 +/- 3.07 pg/ml per 106 cells at baseline vs 27.66 +/- 2.03 pg/ml per 106 cells after treatment) and perilesional MSCs (235.03 +/- 2.52 pg/ml per 106 cells vs 41.65 +/- 4.72 pg/ml per 106 cells). CONCLUSIONS: Etanercept reduces the production of VEGF in MSCs, which may modulate angiogenesis and contributes towards preventing the start of the "psoriatic march". PMID- 27683132 TI - Salivary interleukin-1beta: Oral inflammatory biomarker in patients with psoriasis. AB - OBJECTIVE: To evaluate salivary interleukin (IL)-1beta levels in patients with psoriasis, before and after treatment with tumour necrosis factor (TNF)-alpha inhibitors. METHODS: In this pilot study, salivary secretions were collected from patients with psoriasis and untreated healthy control subjects at baseline, and from patients after 12 weeks' treatment with TNF-alpha inhibitors. IL-1beta levels were determined in saliva samples via enzyme-linked immunosorbent assays, undertaken before and after TNF-alpha inhibitor treatment. Psoriasis-specific analysis of disease severity and activity were also undertaken. RESULTS: At baseline, patients (n = 25) had significantly higher salivary IL1beta levels than controls (n = 20). In patients with psoriasis, TNF-alpha inhibitor treatment resulted in significantly reduced IL1beta levels compared with baseline, but IL1beta levels remained significantly higher than in control subjects even after treatment. There was a positive correlation between IL-1beta levels, psoriasis activity and disease index score after TNF-alpha inhibitor treatment. CONCLUSION: Saliva is a valid noninvasive tool for monitoring inflammation in psoriasis. TNF alpha inhibitor treatments appear to interfere with the oral inflammatory process in patients with psoriasis. PMID- 27683133 TI - Synovial fluid from patients with rheumatoid arthritis modulates monocyte cell surface phenotype. AB - OBJECTIVES: To investigate the ability of synovial fluid from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) to modulate cell-surface phenotype, function and viability of monocytes. METHODS: Monocytes from healthy donors were incubated with synovial fluid from patients with RA or OA. These were then cultured with autologous healthy CD4+ T-cells. Immunoglobulin-like transcript 4 (ILT4) and CD86 were evaluated on stimulated monocytes and CD4+ T cells via fluorescence activated cell sorting. RESULTS: Monocytes incubated with synovial fluid from patients with RA (SF-RA; n = 12) had significantly lower ILT4 and higher CD86 levels than those incubated with synovial fluid from patients with OA (SF-OA; n = 12) or medium alone. In patients with RA, there was a significant negative correlation between ILT4 and disease activity score (DAS; r = -0.699), and a positive correlation between CD86 and DAS (r = 0.626). T-cells costimulated with monocytes cultured with SF-RA produced significantly more interferon-gamma and tumour necrosis factor-alpha than those costimulated with monocytes cultured with SF-OA or controls. CONCLUSIONS: Soluble mediators in SF RA could contribute to modulating inflammation and local effectiveness of the immune response. PMID- 27683134 TI - Expression of immunoglobulin-like transcript 4 as an inhibitory receptor in patients with psoriatic arthritis. AB - OBJECTIVES: To investigate the presence of immunoglobulin-like transcript (ILT)4 and costimulatory proteins (CD40, CD80 and CD86), as well as tumour necrosis factor (TNF)-alpha production in antigen-presenting cells (APCs) from patients with psoriatic arthritis, before and after treatment with the antitumour necrosis factor-alpha therapy, adalimumab. METHODS: Peripheral blood monocytes from patients with psoriatic arthritis and healthy controls were cultured with CD40 ligand (CD40L) to stimulate differentiation to APCs. Cell-surface phenotype was analysed via fluorescence-activated cell sorting. RESULTS: CD40L-stimulation resulted in significantly more ILT4+ monocytes in cultures from control subjects (n = 21) than those from patients (n = 20). ILT4-positivity on CD40L-stimulated monocytes was negatively correlated with disease activity in patients. Adalimumab treatment resulted in significant increases from baseline in ILT4-positivity, and in decreases in CD40, CD80 and CD86-positivity in monocytes from patients. CONCLUSION: The effect of adalimumab on monocyte surface phenotype may be due to modification of the inflammatory milieu associated with therapy-induced reduction of disease activity in psoriatic arthritis. PMID- 27683136 TI - S100A8/A9 in psoriatic plaques from patients with psoriatic arthritis. AB - OBJECTIVE: To evaluate levels of the calcium-binding proteins S100A8 and S100A9 in the skin of patients with psoriatic arthritis. METHODS: Skin punch biopsies were obtained from patients with psoriatic arthritis and healthy control subjects. S100A8/A9 were semiquantified via immunohistochemistry and semiquantitative polymerase chain reaction. RESULTS: The study included biopsies from nine patients with psoriatic arthritis and nine control subjects. S100A8 and S100A9 were present at visibly higher levels in psoriatic plaques compared with normal skin samples. S100A8 and S100A9 RNA levels were significantly higher in the peripheral region of plaques compared with the central region. CONCLUSION: Both S100A8 and S100A9 may represent good therapeutic targets in psoriasis and psoriatic arthritis. PMID- 27683135 TI - Effective tumour necrosis factor-blocking therapy reduces reactive oxygen metabolite level in rheumatoid arthritis. AB - OBJECTIVE: To assess circulating levels of derived reactive oxygen metabolites (ROMs) in patients with active rheumatoid arthritis (RA), before and during antitumour necrosis factor (TNF)-alpha therapy. METHODS: Patients with active RA and failed previous treatment with disease-modifying antirheumatic drugs received subcutaneous anti-TNF-alpha for 52 weeks. Circulating hydrogen peroxide was quantified as a marker of oxidative stress at baseline and at 24 and 52 weeks. RESULTS: The study included 40 patients. Circulating dROM levels were significantly reduced compared with baseline after 24 and 52 weeks' of anti-TNF alpha treatment (33.2 +/- 10.0 mgH2O2/dl, 29.5 +/- 7.0 mgH2O2/dl and 29.3 +/- 9.0 mgH2O2/dl, respectively). There was a significant direct correlation between disease activity score and ROM levels. CONCLUSION: TNF-alpha inhibition can control disease activity and reduce circulating levels of reactive oxygen species in patients with RA. PMID- 27683137 TI - How the immune system responds to therapeutic biological agents. AB - Biological agents target disease mechanisms and have modified the natural history of several immune-mediated disorders. Biological agents are structurally immunogenic, and therefore usually elicit a minor, subclinical and transient phenomenon. Occasionally, however, these drugs induce complete cellular and humoral immune responses, with the main clinical consequences being hypersensitivity reactions or loss of treatment response. This article considers the relative pathogenic mechanisms influencing immunogenicity in biological agents and discusses mechanisms of tolerance and adaptive immune response, including adaptive T-regulatory cell induction and immune response induction. Methods of determining cellular and humoral immune response to biological agents are identified and examined. Assays to detect antidrug antibodies and their isotypes can assist in monitoring immunogenicity and in preventing adverse events. Such strategies also enable resource conservation and may provide regulatory authorities with new insights that can be useful during the process of approving new biological or biosimilar agents. PMID- 27683138 TI - Cardiovascular risk evaluation through heart rate variability analysis in psoriatic patients before and after 24 weeks of etanercept therapy: Prospective study. AB - OBJECTIVE: To assess the influence of etanercept, an anti-tumour necrosis factor (TNF)-alpha agent, on autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. METHODS: Patients with psoriasis underwent 5-min electrocardiogram (ECG) recordings before and after 24 weeks of etanercept therapy. Linear heart rate variability (HRV) analysis was performed. RESULTS: The study recruited 19 patients. Frequency domain analysis showed a significant decrease in oscillatory components attributable to sympathetic activity (LF%) and a significant decrease in low frequency/high frequency (LF/HF) ratio following etanercept therapy. CONCLUSION: Treatment with etanercept in patients with moderate-to-severe psoriasis could affect cardiovascular autonomic regulation, and subsequently reduce cardiovascular risk. PMID- 27683139 TI - Long-term treatment with adalimumab in psoriatic arthritis: serum adalimumab concentration, immunogenicity and the link with clinical response. AB - OBJECTIVES: An observational study to evaluate the relationship between serum concentrations of adalimumab and disease activity in patients receiving long-term adalimumab treatment for psoriatic arthritis. METHODS: Serum adalimumab and adalimumab antidrug antibodies were quantified by enzyme linked immunosorbent assay. Disease activity was assessed using Disease Activity Score (44 joint measures). Serum C-reactive protein was quantified using standard methods. RESULTS: A total of 30 patients were recruited. There were significant inverse correlations between serum adalimumab concentration and serum C-reactive protein (CRP) concentration [r = -0.43], the number of tender joints (r = -0.4), and Disease Activity Score (DAS44)-CRP (r = -0.36). Mean serum adalimumab levels were significantly higher in patients with DAS44-CRP <1.6 than in patients with DAS44 CRP >=1.6. CONCLUSIONS: Serum adalimumab could be an important tool that may improve the management of psoriatic arthritis in patients responding to long-term treatment. PMID- 27683128 TI - Circulating and disseminated tumor cells: diagnostic tools and therapeutic targets in motion. AB - Enumeration of circulating tumor cells (CTCs) in peripheral blood with the gold standard CellSearchTM has proven prognostic value for tumor recurrence and progression of metastatic disease. Therefore, the further molecular characterization of isolated CTCs might have clinical relevance as liquid biopsy for therapeutic decision-making and to monitor disease progression. The direct analysis of systemic cancer appears particularly important in view of the known disparity in expression of therapeutic targets as well as epithelial-to mesenchymal transition (EMT)-based heterogeneity between primary and systemic tumor cells, which all substantially complicate monitoring and therapeutic targeting at present. Since CTCs are the potential precursor cells of metastasis, their in-depth molecular profiling should also provide a useful resource for target discovery. The present review will discuss the use of systemically spread cancer cells as liquid biopsy and focus on potential target antigens. PMID- 27683140 TI - Serological markers associated with disease activity in patients with rheumatoid arthritis treated with rituximab. AB - OBJECTIVE: To evaluate prospectively serological markers at baseline and during treatment in patients with rheumatoid arthritis (RA) initiating rituximab treatment, following failure of antitumour necrosis factor (TNF)-alpha therapy. METHODS: Patients with RA and healthy control subjects were recruited. Plasma complement (C)3, C4, rheumatoid factor (RF), anticitrullinated protein antibody (ACPA), immunoglobulin (Ig)M, A and G, disease activity scores (DAS) and therapeutic response were recorded at baseline and at 6, 12 and 18 months. RESULTS: Patients (n = 35) had significantly higher C3 and C4 levels than controls (n = 30). At 12 months after initiation of rituximab, C3 and C4 levels were significantly lower in patients who responded to treatment, compared with nonresponders. There were direct correlations between C3 levels and DAS at 12 months in the study population as a whole, and between IgM levels and DAS in responding patients after 6, 12 and 18 months' treatment. CONCLUSIONS: C3 and IgM levels may represent potentially useful serological markers of disease activity during rituximab treatment in patients with RA. PMID- 27683141 TI - Long-term safety of etanercept in psoriasis: Retrospective study focused on infections. AB - OBJECTIVE: Retrospective study to evaluate the incidence of infectious adverse events in patients with psoriasis treated with etanercept. METHODS: Patients with psoriasis or psoriatic arthritis who were treated with etanercept (50 mg, administered weekly via subcutaneous injection) for >=48 weeks were retrospectively enrolled. Patients were screened for occult infections before treatment commenced, and then every 12 months thereafter. Minor (not requiring hospitalization and/or discontinuation of treatment) and major (requiring hospitalization and/or discontinuation of treatment) infectious events were recorded. RESULTS: The study included 50 patients. Minor infectious events included self-limiting upper respiratory tract infections (six patients), lower urinary tract infections (one patient) and recurrent herpes simplex labialis (two patients). Major infections occurred in only two cases. CONCLUSION: These data support the good safety profile of etanercept in patients with psoriasis or psoriatic arthritis. PMID- 27683142 TI - Suicide risk and psychiatric comorbidity in patients with psoriasis. AB - OBJECTIVES: To examine the occurrence of stressful life events, psychological comorbidity and suicide risk in patients with psoriasis or other dermatological conditions. METHODS: Consecutive adult outpatients with psoriasis or other dermatological conditions completed a sociodemographic questionnaire and the Hamilton scales for depression and anxiety. RESULTS: The study included 157 patients (91 with psoriasis; 66 with other conditions [melanoma; allergy]). Patients with psoriasis were significantly more likely to have experienced major life events in the 12 months before diagnosis, have had a psychiatric diagnosis and to have experienced past suicidal ideation than patients with other dermatological conditions. CONCLUSIONS: Patients with psoriasis have an increased risk of psychiatric comorbidities, suicidal ideation, and long-term course of the disease compared with patients who have other dermatological conditions. Psychiatric assessment is highly recommended in patients with psoriasis. PMID- 27683143 TI - Treatment of psoriasis with etanercept in immunocompromised patients: Two case reports. AB - Tumour necrosis factor (TNF)-alpha blocking agents have revolutionized the treatment of psoriasis and psoriatic arthritis. Concerns remain about increased susceptibility to infection and onset of malignancies, and the use of TNF-alpha agents in patients with HIV infection or undergoing immunosuppressant treatment is debated. We report cases of severe plaque psoriasis in a patient with HIV infection and in a liver transplant recipient who were successfully treated with etanercept, an anti-TNF-alpha agent, without notable side-effects. PMID- 27683144 TI - Influence of body mass index and weight on etanercept efficacy in patients with psoriasis: A retrospective study. AB - AIM: To investigate the role of body mass index (BMI) and weight in the long-term efficacy of etanercept in patients with psoriasis. METHODS: Medical records were retrospectively analysed. Extracted data included weight, BMI, comorbidities and psoriasis area severity index (PASI). Patients were stratified by weight (<80 kg or >=80 kg) and BMI (healthy, BMI 22 - 24.99 kg/m2; overweight, BMI 25 - 29.99 kg/m2; obese, BMI >=30 kg/m2). RESULTS: The study included 66 patients. Body weight had no effect on etanercept efficacy. There was a significant reduction in etanercept efficacy in obese patients (n = 12) compared with healthy weight (n = 33) or overweight (n = 21) patients. CONCLUSION: Obesity has a negative effect on the efficacy of etanercept in psoriasis. PMID- 27683145 TI - Asymmetric dimethylarginine and arterial stiffness in patients with rheumatoid arthritis: A case-control study. AB - OBJECTIVE: To investigate whether levels of asymmetric dimethylarginine (ADMA), as a measure of endothelial dysfunction, are higher in patients with rheumatoid arthritis compared with healthy control subjects. The relationships between ADMA and surrogate measures of arterial stiffness were evaluated. METHODS: Patients with rheumatoid arthritis and healthy control subjects were recruited. ADMA was quantified via enzyme-linked immunosorbent assay. Arterial stiffness was evaluated using pulse wave analysis. RESULTS: There was no significant difference in plasma ADMA concentration between patients with rheumatoid arthritis (n = 30) and healthy controls (n = 30). Aortic augmentation pressure was significantly higher in patients than in controls. C-reactive protein and Health Assessment Questionnaire score were independent predictors of arterial stiffness in patients. There was no relationship between ADMA concentration and aortic augmentation pressure in the study population as a whole. CONCLUSIONS: Arterial stiffness appears to be increased in rheumatoid arthritis and independently associated with systemic inflammation and physical disability. ADMA concentration was not increased in this small group of patients with rheumatoid arthritis compared with healthy controls; nor was it associated with arterial stiffness. PMID- 27683146 TI - Post-translational modifications in rheumatoid arthritis and atherosclerosis: Focus on citrullination and carbamylation. AB - Coronary heart disease is the main cause of mortality in patients with rheumatoid arthritis (RA), a disease known to be associated with accelerated atherosclerosis. The role of inflammation and immunity in atherosclerotic process offers possible explanations for the increased cardiovascular risk in patients with RA. The immune response to citrullinated peptides has been extensively studied in RA; antibodies directed to citrullinated peptides are now a cornerstone for RA diagnosis. However, few studies have investigated the response to citrullinated peptides and the development of atherosclerotic plaque. Antibodies to carbamylated proteins can be detected before the clinical onset of RA, suggesting a potential predictive role for these antibodies; on the other hand, carbamylation of lipoproteins has been described in patients with cardiovascular disease. This review examines the role of citrullination and carbamylation, two post-translational protein modifications that appear to be involved in the pathogenesis of both RA and atherosclerosis, expanding the similarities between these two diseases. Further investigation on the role of the immune response to modified proteins may contribute to a better comprehension of cardiovascular disease in patients with RA. PMID- 27683147 TI - Beneficial effects of long-term treatment with bosentan on the development of pulmonary arterial hypertension in patients with systemic sclerosis. AB - OBJECTIVE: To investigate the effects of long-term treatment with bosentan on pulmonary arterial hypertension (PAH) in patients with systemic sclerosis. METHODS: Patients with systemic sclerosis were followed between 2003 and 2014; those who developed digital ulcers were treated with standard regimens of bosentan. Patients were assessed at baseline and every 12 months using transthoracic Doppler echocardiography, 6-min walking distance test, Borg dyspnoea index and monitoring of plasma levels of 76-amino-acid N-terminal probrain natriuretic peptide. Patients who developed PAH underwent right heart catheterization to confirm the diagnosis. RESULTS: Sixty-nine patients with systemic sclerosis were enrolled in the study. Of these, 25 developed digital ulcers and received treatment with bosentan; the remaining 44 comprised the control group. None of the patients treated with bosentan developed PAH during the follow-up period. Furthermore, in these patients the mean +/- SD systolic pulmonary arterial pressure significantly decreased from 33.64 +/- 2.91 mmHg at baseline to 26.20 +/- 1.78 mmHg at the end of the follow-up period. In contrast, in the control group, seven patients developed PAH during the follow-up period, with the mean +/- SD systolic pulmonary arterial pressure significantly increasing from 33.57 +/- 2.75 mmHg at baseline to 39.41 +/- 4.11 mmHg at the end of the follow-up period. CONCLUSION: Long-term treatment with bosentan reduces the risk of developing PAH in patients with systemic sclerosis. PMID- 27683148 TI - Remission and low disease activity in a cohort of real-life patients with rheumatoid arthritis treated with first-line antitumour necrosis factor. AB - OBJECTIVES: This retrospective study used various indices to evaluate remission and low disease activity in 'real life' patients with rheumatoid arthritis (RA), given antitumour necrosis factor (anti-TNF) as a first-line treatment; changes in concomitant steroid and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment were also assessed. METHODS: Remission and low disease activity were analysed in patients with RA treated with anti-TNF using the 28 joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). Remission and low disease activity were recorded after 6 months, 1 year and 2 years, along with concomitant prednisone and csDMARD treatment. RESULTS: A total of 271 patients with RA were included in the study. After 6 months, remission rates were 18.0%, 20.3% and 23.0% as assessed by CDAI, SDAI and DAS28, respectively. After 1 year and 2 years, respectively, remission rates were 18.4% and 15.9% using CDAI, 21.8% and 17.3% using SDAI, and 22.1% and 17.3% using DAS28. Low disease activity was achieved in 30-40% of patients, depending on the indices used. There was a significant reduction in the number of patients on prednisone and csDMARDs during anti-TNF treatment. CONCLUSION: Remission with first-line anti-TNF treatment is an achievable goal in clinical practice, allowing a reduction in concomitant csDMARD and prednisone treatment. PMID- 27683149 TI - From patients' needs to treatment outcomes in psoriasis: Results from the 'pSORRIDI' experience. AB - OBJECTIVE: To evaluate results of the 'pSORRIDI' experience (which is a prevention campaign to evaluate the prevalence of comorbidities, multidisciplinary needs and appropriateness of the therapeutic approach for comorbidities) in patients already being treated for psoriasis. METHODS: Telephone interviews were conducted in patients with psoriasis, who then underwent comprehensive evaluation and investigation of comorbidities. If necessary, patients were referred to specialist cardiology, endocrinology and/or rheumatology services. RESULTS: Overall, 72.0% (54/75) of patients required a multidisciplinary consultation. Among patients referred to cardiology, therapeutic adjustment was needed in 33.3% (five of 15) patients and a redefined diagnosis in 26.7% (four of 15) cases. Among patients undergoing endocrinology evaluations, therapeutic adjustment and a redefined diagnosis were needed in 61.1% (11/18) and 33.3% (six of 18) patients, respectively; for rheumatology evaluations, therapeutic adjustment and a redefined diagnosis were needed in 76.2% (16/21) and 19.0% (four of 21) of patients, respectively. CONCLUSIONS: Among patients with psoriasis, there may be a need for an improvement in the diagnosis of underlying comorbid conditions, and in disease management of both psoriasis and any comorbid conditions. PMID- 27683150 TI - Combination therapy with etanercept in psoriasis: Retrospective analysis of efficacy and safety outcomes from real-life practice. AB - OBJECTIVE: To investigate the efficacy and safety outcomes of combination therapy used to optimize etanercept treatment in patients with psoriasis treated in real life clinical practice. METHODS: Data from patients presenting with psoriasis, treated initially with etanercept monotherapy, were analysed retrospectively. Patients subsequently treated with combination therapy were further analysed. The Psoriasis Area and Severity Index (PASI) score was recorded for all patients receiving comedication; a subjective pain score was recorded in those with psoriatic arthritis receiving comedication after 12, 24 and 48 weeks' treatment and thereafter at 6-month intervals. RESULTS: From the database of 400 patients treated with etanercept, 37 patients (18 male; 19 female; mean age 59.43 years) underwent combination therapy due to lack of efficacy. Patients received mostly short-term (range 4-34 weeks) comedication with corticosteroids, cyclosporine, methotrexate, nonsteroidal anti-inflammatory drugs, acitretin or sulphasalazine. There were significant reductions in the mean PASI score from baseline at all timepoints. There were also significant reductions in the mean pain VAS score from baseline at all timepoints in patients with psoriatic arthritis. The drug survival rate was 59.6% over a mean duration of 323 weeks of etanercept treatment. The safety profile of combination therapy was satisfactory. CONCLUSIONS: Short-term comedication in combination with etanercept may optimize treatment options and improve long-term drug survival in patients with psoriasis. PMID- 27683151 TI - Glomerular filtration rate in patients with psoriasis treated with etanercept. AB - OBJECTIVE: To estimate the prevalence of chronic kidney disease (CKD) and evaluate renal function in patients with moderate-to-severe chronic plaque psoriasis treated with etanercept (an anti-tumour necrosis factor-alpha drug). METHODS: This retrospective cohort study included patients with moderate-to severe chronic plaque psoriasis. Kidney function was evaluated using estimated glomerular filtration rate (EGFR). RESULTS: The prevalence of CKD at baseline was 3.9% (two of 51 patients). EGFR was unaffected by etanercept therapy (83.6 +/- 23.9 at baseline vs 82.2 +/- 21.6 ml/min per 1.73 m2 after 6 months). CONCLUSION: EGFR was unaffected by 6 months' etanercept treatment. Physicians should be aware of the risk of CKD when providing comprehensive care to patients with moderate-to severe psoriasis. PMID- 27683152 TI - Long-term efficacy of high doses of intravenous immunoglobulins in generalized scleromyxoedema: Case report. AB - Scleromyxoedema is a rare disease with a progressive and disabling course involving dermal deposition of mucin and fibroblast proliferation; it is characterized clinically by a diffuse papular eruption, skin thickening, oedema and decreased skin flexibility, especially of the face and hands. Current therapy options are based on evidence from a limited number of case reports. The clinical manifestations and treatment of a 64-year-old man affected by scleromyxoedema with severe skin involvement of the face, arms and hands, decreased mouth opening and hypomotility of the fingers are reported. Dysphagia, asthenia and immunoglobulin G lambda monoclonal gammopathy were also present. Previous treatment with topical and systemic corticosteroids, psoralen plus ultraviolet A radiation therapy, plasmapheresis, extracorporeal photochemotherapy, hydroxychloroquine and cyclophosphamide had been unsuccessful. Treatment with intravenous immunoglobulins at a dosage of 2 g/kg monthly was started. Considerable improvements were observed after seven cycles of therapy, with recovery of skin elasticity, an increase in facial mimic movement, restoration of joint function and improvement in the modified Rodnan score. There were no observed side-effects. The patient remains in remission on monthly maintenance intravenous immunoglobulins, 2 years after initial treatment. PMID- 27683154 TI - Speckled variance optical coherence tomography for the assessment of nail involvement in acrodermatitis continua of Hallopeau: A case study. AB - Noninvasive techniques for nail imaging would be useful for confirming diagnosis and monitoring treatment response at the microscopic level in patients with nail psoriasis. However, the use of ultrasound and high-resolution magnetic resonance imaging in nail evaluation is limited. Optical coherence tomography (OCT) produces high-resolution images of transversal tissue sections and represents an optimal approach to the study of the nail. This study used a multibeam OCT instrument to produce speckled variance OCT (SV-OCT) blood-flow images, which were used to measure the degree of change over successive scans. Nail changes, inflammation and response to therapy were evaluated in a 75-year-old female patient with psoriasis who had severe acrodermatitis continua of Hallopeau of the hands, treated for 4 weeks with 40 mg adalimumab (administered subcutaneously every other week) and 25 mg prednisone (administered orally, daily). SV-OCT provided a detailed assessment of the nail structures in relation to inflammation of psoriatic tissues. Restoration of the normal anatomy of the nail apparatus was apparent following adalimumab treatment; SV-OCT evaluation correlated with clinical appearance. SV-OCT may have a diagnostic role and provide an objective tool to assess clinical and subclinical inflammation in nail psoriasis. PMID- 27683153 TI - The role of methotrexate as combination therapy with etanercept in rheumatoid arthritis: Retrospective analysis of a local registry. AB - OBJECTIVE: In a real-life setting, to analyse retrospectively the effects of different methotrexate regimens on etanercept efficacy during the first year of treatment for rheumatoid arthritis (RA). METHODS: Demographic characteristics, clinical parameters and treatment data from patients with RA receiving the first line biological disease-modifying antirheumatic drug, etanercept, as monotherapy or in combination with methotrexate were analysed at baseline and after 6 and 12 months. The study population was stratified into three groups according to the level of concomitant methotrexate therapy: no methotrexate, low-dose methotrexate (<= 10 mg/week) or high-dose methotrexate (>10 mg/week). RESULTS: Clinical response at 6 and 12 months and clinical outcome at 12 months were significantly better in patients concomitantly treated with high-dose methotrexate. Furthermore, this regimen was associated with the lowest discontinuation rate, suggesting a favourable safety profile. CONCLUSION: These data confirm, in a real life setting, the importance of methotrexate as a combination therapy with etanercept and suggest that the minimal effective dose of methotrexate is >10 mg/week. PMID- 27683155 TI - Exploration of pathomechanisms triggered by a single-nucleotide polymorphism in titin's I-band: the cardiomyopathy-linked mutation T2580I. AB - Missense single-nucleotide polymorphisms (mSNPs) in titin are emerging as a main causative factor of heart failure. However, distinguishing between benign and disease-causing mSNPs is a substantial challenge. Here, we research the question of whether a single mSNP in a generic domain of titin can affect heart function as a whole and, if so, how. For this, we studied the mSNP T2850I, seemingly linked to arrhythmogenic right ventricular cardiomyopathy (ARVC). We used structural biology, computational simulations and transgenic muscle in vivo methods to track the effect of the mutation from the molecular to the organismal level. The data show that the T2850I exchange is compatible with the domain three dimensional fold, but that it strongly destabilizes it. Further, it induces a change in the conformational dynamics of the titin chain that alters its reactivity, causing the formation of aberrant interactions in the sarcomere. Echocardiography of knock-in mice indicated a mild diastolic dysfunction arising from increased myocardial stiffness. In conclusion, our data provide evidence that single mSNPs in titin's I-band can alter overall muscle behaviour. Our suggested mechanisms of disease are the development of non-native sarcomeric interactions and titin instability leading to a reduced I-band compliance. However, understanding the T2850I-induced ARVC pathology mechanistically remains a complex problem and will require a deeper understanding of the sarcomeric context of the titin region affected. PMID- 27683156 TI - Prediction and validation of protein-protein interactors from genome-wide DNA binding data using a knowledge-based machine-learning approach. AB - The ability to accurately predict the DNA targets and interacting cofactors of transcriptional regulators from genome-wide data can significantly advance our understanding of gene regulatory networks. NKX2-5 is a homeodomain transcription factor that sits high in the cardiac gene regulatory network and is essential for normal heart development. We previously identified genomic targets for NKX2-5 in mouse HL-1 atrial cardiomyocytes using DNA-adenine methyltransferase identification (DamID). Here, we apply machine learning algorithms and propose a knowledge-based feature selection method for predicting NKX2-5 protein : protein interactions based on motif grammar in genome-wide DNA-binding data. We assessed model performance using leave-one-out cross-validation and a completely independent DamID experiment performed with replicates. In addition to identifying previously described NKX2-5-interacting proteins, including GATA, HAND and TBX family members, a number of novel interactors were identified, with direct protein : protein interactions between NKX2-5 and retinoid X receptor (RXR), paired-related homeobox (PRRX) and Ikaros zinc fingers (IKZF) validated using the yeast two-hybrid assay. We also found that the interaction of RXRalpha with NKX2-5 mutations found in congenital heart disease (Q187H, R189G and R190H) was altered. These findings highlight an intuitive approach to accessing protein protein interaction information of transcription factors in DNA-binding experiments. PMID- 27683158 TI - Low calcium and vitamin D intake in Korean women over 50 years of age. AB - Inadequate calcium and vitamin D intake is a possible risk factor of osteoporosis. Our purposes were to estimate calcium and vitamin D intake in Korean women, and to determine associated risk factors for low calcium and vitamin D intake. This is a multicenter, hospital-based, and cross-sectional study on osteoporosis. In this study, 1516 women of 50 years or older were involved. Dietary calcium and vitamin D intake were evaluated using the self reporting KCAT questionnaire. Average daily calcium intake was 662.8 +/- 473.8 mg, and vitamin D intake 9.5 +/- 10.7 MUg. In multivariate analysis, older age (OR 1.02, 95 % CI 1.00-1.04, p = 0.001), and rural residence (OR 2.43, 95 % CI 1.34-4.43, p = 0.004) were significant risk factors for lower calcium intake, and older age (OR 1.03, 95 % CI 1.02-1.04, p < 0.001), and rural residence (OR 1.85, 95 % CI 1.10-3.11, p < 0.001) were significant risk factors for lower vitamin D intake. About 70 % of women aged 50 years or older had calcium and vitamin D intake below the recommended dietary intake. Older age and rural residence were significant risk factors for lower calcium and vitamin D intake in Korean women. PMID- 27683157 TI - Challenging perspectives on the cellular origins of lymphoma. AB - Both B and T lymphocytes have signature traits that set them apart from other cell types. They actively and repeatedly rearrange their DNA in order to produce a unique and functional antigen receptor, they have potential for massive clonal expansion upon encountering antigen via this receptor or its precursor, and they have the capacity to be extremely long lived as 'memory' cells. All three of these traits are fundamental to their ability to function as the adaptive immune response to infectious agents, but concurrently render these cells vulnerable to transformation. Thus, it is classically considered that lymphomas arise at a relatively late stage in a lymphocyte's development during the process of modifying diversity within antigen receptors, and when the cell is capable of responding to stimulus via its receptor. Attempts to understand the aetiology of lymphoma have reinforced this notion, as the most notable advances to date have shown chronic stimulation of the antigen receptor by infectious agents or self antigens to be key drivers of these diseases. Despite this, there is still uncertainty about the cell of origin in some lymphomas, and increasing evidence that a subset arises in a more immature cell. Specifically, a recent study indicates that T-cell lymphoma, in particular nucleophosmin-anaplastic lymphoma kinase-driven anaplastic large cell lymphoma, may originate in T-cell progenitors in the thymus. PMID- 27683161 TI - Your views on leader visibility. PMID- 27683159 TI - Regional tau deposition measured by [18F]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer's disease. AB - BACKGROUND: The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([18F]THK5317-PET) and metabolism ([18F]FDG-PET) with concomitant cognitive function in patients with probable Alzheimer's disease (AD). METHODS: Nine patients diagnosed with AD dementia and 11 with prodromal AD (mild cognitive impairment, amyloid-positive on [11C]PiB-PET) were included in this study. All patients underwent PET scans using each tracer, as well as episodic memory and global cognition assessment. Linear models were used to investigate the association of regional [18F]THK5317 retention and [18F]FDG uptake with cognition. The possible mediating effect of local metabolism on the relationship between tau deposition and cognitive performance was investigated using mediation analyses. RESULTS: Significant negative associations were found between [18F]THK5317 regional retention, mainly in temporal regions, and both episodic memory and global cognition. Significant positive associations were found between [18F]FDG regional uptake and cognition. The association of [18F]FDG with global cognition was regionally more extensive than that of [18F]THK5317, while the opposite was observed with episodic memory, suggesting that [18F]THK5317 retention might be more sensitive than [18F]FDG regional uptake to early cognitive impairment. Finally, [18F]FDG uptake had a mediating effect on the relationship between [18F]THK5317 retention in temporal regions and global cognition. CONCLUSIONS: These findings suggest a mediating role for local glucose metabolism in the observed association between in vivo tau deposition and concomitant cognitive impairment in AD. PMID- 27683162 TI - Nursing practice remediation: Administration and regulation. PMID- 27683163 TI - Better outcomes through "rooming-in". PMID- 27683164 TI - The value of free clinics. PMID- 27683165 TI - Seven strategies for partnering with risk managers. PMID- 27683166 TI - Leadership, defined: What's your style, and how's it actually perceived? PMID- 27683167 TI - The mindful nurse leader: Advancing executive nurse leadership skills through participation in action learning. AB - In this second installment of a three-part series on mindfulness, we describe the process of producing video vignettes to illustrate how clinical nurses draw on the power of mindfulness to build their own resiliency while delivering compassionate care. PMID- 27683168 TI - Improve manager competency with experiential learning. PMID- 27683169 TI - Leadership Q&A. PMID- 27683171 TI - Outcomes in Premature Acute Coronary Syndrome: Has the Sex Gap Closed? PMID- 27683170 TI - Molecular analysis of the hexon, penton base, and fiber-2 genes of Korean fowl adenovirus serotype 4 isolates from hydropericardium syndrome-affected chickens. AB - Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome (HPS), a highly pathogenic disease in poultry. In the present study, hexon, penton base, and fiber-2 genes encoding major capsid proteins were analyzed in four FAdV-4 isolates from HPS-affected chickens in Korea. Nucleotide sequences of the entire hexon (2811 bases), penton base (1578 bases), and fiber-2 (1425 bases) genes from the Korean isolates were 97.5-99.3, 99.1-99.7, and 95.5 99.0 % identical, respectively, to those of foreign FAdV-4 isolates. In the N terminal tail region of fiber-2, the KRP motif predicted to be the nuclear localization signal was identified in the Korean isolates, whereas KRP/A was detected in other isolates. The VYPF motif in fiber-2, which is known to interact with the penton base, was present in the same region of all FAdV-4 isolates that were compared. Amino acid variations in fiber-2 for HPS and non-HPS isolates revealed that D219 and T300 were conserved among ten HPS isolates from five countries, including Korea. T380 in fiber-2, previously found in HPS isolates, corresponded to A380 in the Korean isolates, indicating that T380 is not relevant for increased virulence. Phylogenetic analysis showed that the four Korean FAdV-4 isolates were more related to MX-SHP95, a Mexican FAdV-4 isolate of HPS origin, than to FAdV-4 isolates of Indian and Chinese origin, suggesting that the genetic relationship among FAdV-4 isolates is independent of geographic distribution. The molecular features of these genes will provide valuable information for vaccine development against HPS in the future. PMID- 27683172 TI - Sex Differences in Clinical Outcomes After Premature Acute Coronary Syndrome. AB - BACKGROUND: Over past decades, the incidence of acute coronary syndrome (ACS) has increased in young women, and greater mortality rates after discharge were observed among young women vs men. We revisited this issue with contemporary data from the Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome (GENESIS-PRAXY), a multicentre prospective cohort study. METHODS: One thousand two hundred thirteen patients were enrolled in GENESIS-PRAXY from 26 centres across Canada, the United States, and Switzerland between January 2009 and April 2013. We assessed major adverse cardiac events (MACE) and mortality over 12 months after ACS. The role of sex as a predictor of outcomes was determined with Cox proportional hazard regression analysis. RESULTS: We included 1163 patients with complete data. The occurrence of MACE was 9% and 8% in women and men, respectively (P = 0.75), and 1% of women and men died during follow-up. In adjusted models, there was no sex difference in the risk of MACE or mortality. The proportion of patients with all-cause rehospitalization was higher in women (13%) compared with men (9%; P = 0.006), but cardiac rehospitalization rates were similar in both sexes regardless of ACS type. Among first rehospitalizations, the majority was classified as cardiac related (69%), with chest pain or angina (28%) and myocardial infarction (19%) reported as the most common reasons for first rehospitalization. CONCLUSIONS: Women were more likely than men to be rehospitalized for all causes but not for a cardiac cause. In contrast to earlier studies, men and women had similar mortality and MACE outcomes at 1 year. PMID- 27683173 TI - Investigating Sociodemographic Factors and HIV Risk Behaviors Associated With Social Networking Among Adolescents in Soweto, South Africa: A Cross-Sectional Survey. AB - BACKGROUND: Internet access via mobile phones and computers facilitates interaction and potential health communication among individuals through social networking. Many South African adolescents own mobile phones and can access social networks via apps. OBJECTIVE: We investigated sociodemographic factors and HIV risk behaviors of adolescent social networking users in Soweto, South Africa. METHODS: We conducted an interviewer-administered, cross-sectional survey of adolescents aged 14-19 years. Independent covariates of social networking were assessed by multivariate logistic regression analysis. RESULTS: Of 830 adolescents, 57% (475/830) were females and the median age was found to be 18 years (interquartile range 17-18). Social networking was used by 60% of adolescents (494/830); more than half, that is, 87% (396/494) accessed social networks through mobile phones and 56% (275/494) spent more than 4 hours per day using their mobile phones. Social networking was independently associated with mobile usage 2-4 hours (adjusted odds ratio [AOR]: 3.06, CI: 1.69-5.51) and more than 4 hours per day (AOR: 6.16, CI: 3.46-10.9) and one (AOR: 3.35, CI: 1.79 6.27) or more sexual partner(s) (AOR: 2.58, CI: 1.05-6.36). CONCLUSIONS: Mobile phone-based social networking is prevalent among sexually active adolescents living in Soweto and may be used as an entry point for health promotion and initiation of low-cost adolescent health interventions. PMID- 27683174 TI - Inducible cardiomyocyte-specific deletion of CaM kinase II protects from pressure overload-induced heart failure. AB - CaM kinase II (CaMKII) has been suggested to drive pathological cardiac remodeling and heart failure. However, the evidence provided so far is based on inhibitory strategies using chemical compounds and peptides that also exert off target effects and followed exclusively preventive strategies. Therefore, the aim of this study was to investigate whether specific CaMKII inhibition after the onset of cardiac stress delays or reverses maladaptive cardiac remodeling and dysfunction. Combined genetic deletion of the two redundant CaMKII genes delta and gamma was induced after the onset of overt heart failure as the result of pathological pressure overload induced by transverse aortic constriction (TAC). We used two different strategies to engineer an inducible cardiomyocyte-specific CaMKIIdelta/CaMKIIgamma double knockout mouse model (DKO): one model bases on tamoxifen-inducible mER/Cre/mER expression under control of the cardiac-specific alphaMHC promoter; the other strategy bases on overexpression of Cre recombinase via cardiac-specific gene transfer through adeno-associated virus (AAV9) under control of the cardiac-specific myosin light chain promoter. Both models led to a substantial deletion of CaMKII in failing hearts. To approximate the clinical situation, CaMKII deletion was induced 3 weeks after TAC surgery. In both models of DKO, the progression of cardiac dysfunction and interstitial fibrosis could be slowed down as compared to control animals. Taken together, we show for the first time that "therapeutic" CaMKII deletion after cardiac damage is sufficient to attenuate maladaptive cardiac remodeling and to reverse signs of heart failure. These data suggest that CaMKII inhibition is a promising therapeutic approach to combat heart failure. PMID- 27683175 TI - Inhibition of cardiac CaMKII to cure heart failure: step by step towards translation? PMID- 27683176 TI - Oral Bisphosphonates and Improved Survival of Breast Cancer. AB - Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96, P = 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684-9. (c)2016 AACR. PMID- 27683178 TI - Anti-PD1-Induced Pneumonitis: Capturing the Hidden Enemy. AB - Anti-PD1 antibodies have led to a therapeutic shift in cancer treatment. Although classically described as "well tolerated," these drugs can lead to severe immune related adverse events. Using CT scan imaging, Nishino and colleagues describe different radiologic patterns and their possible relation to severity of several cases of anti-PD1-induced pneumonitis. Clin Cancer Res; 22(24); 5956-8. (c)2016 AACRSee related article by Nishino et al., p. 6051. PMID- 27683177 TI - Liver Microvascular Injury and Thrombocytopenia of Antibody-Calicheamicin Conjugates in Cynomolgus Monkeys-Mechanism and Monitoring. AB - Purpose: Adverse reactions reported in patients treated with antibody calicheamicin conjugates such as gemtuzumab ozogamicin (Mylotarg) and inotuzumab ozogamicin include thrombocytopenia and sinusoidal obstruction syndrome (SOS). The objective of this experimental work was to investigate the mechanism for thrombocytopenia, characterize the liver injury, and identify potential safety biomarkers.Experimental Design: Cynomolgus monkeys were dosed intravenously at 6 mg/m2/dose once every 3 weeks with a nonbinding antibody-calicheamicin conjugate (PF-0259) containing the same linker-payload as gemtuzumab ozogamicin and inotuzumab ozogamicin. Monkeys were necropsied 48 hours after the first administration (day 3) or 3 weeks after the third administration (day 63).Results: PF-0259 induced acute thrombocytopenia (up to 86% platelet reduction) with nadirs on days 3 to 4. There was no indication of effects on megakaryocytes in bone marrow or activation of platelets in peripheral blood. Microscopic evaluation of liver from animals necropsied on day 3 demonstrated midzonal degeneration and loss of sinusoidal endothelial cells (SECs) associated with marked platelet accumulation in sinusoids. Liver histopathology on day 63 showed variable endothelial recovery and progression to a combination of sinusoidal capillarization and sinusoidal dilation/hepatocellular atrophy, consistent with early SOS. Among biomarkers evaluated, there were early and sustained increases in serum hyaluronic acid (HA) that correlated well with serum aspartate aminotransferase and liver microscopic changes, suggesting that HA may be a sensitive diagnostic marker of the liver microvascular injury.Conclusions: These data support the conclusion that target-independent damage to liver SECs may be responsible for acute thrombocytopenia (through platelet sequestration in liver sinusoids) and development of SOS. Clin Cancer Res; 23(7); 1760-70. (c)2016 AACR. PMID- 27683179 TI - A Potent In Vivo Antitumor Efficacy of Novel Recombinant Type I Interferon. AB - Purpose: Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the in vitro and in vivo antitumorigenic activities of a novel recombinant IFN termed sIFN-I.Experimental Design: We compared primary and tertiary structures of sIFN-I with its parental human IFNalpha-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK-STAT signaling and expression of the IFN1 stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models.Results: sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNalpha-2b, sIFN-I induced JAK-STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8+ T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice.Conclusions: These findings define sIFN I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. Clin Cancer Res; 23(8); 2038-49. (c)2016 AACR. PMID- 27683181 TI - Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma. AB - Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor-stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1-5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies. Clin Cancer Res; 23(4); 1060-7. (c)2016 AACR. PMID- 27683180 TI - Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors. AB - Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors.Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs.Results: WES revealed TP53 mutations involving p53's DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53-mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53-coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant.Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852-61. (c)2016 AACR. PMID- 27683183 TI - RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. AB - Purpose: Aberrations in genetic sequences encoding the tyrosine kinase receptor RET lead to oncogenic signaling that is targetable with anti-RET multikinase inhibitors. Understanding the comprehensive genomic landscape of RET aberrations across multiple cancers may facilitate clinical trial development targeting RETExperimental Design: We interrogated the molecular portfolio of 4,871 patients with diverse malignancies for the presence of RET aberrations using Clinical Laboratory Improvement Amendments-certified targeted next-generation sequencing of 182 or 236 gene panels.Results: Among diverse cancers, RET aberrations were identified in 88 cases [1.8% (88/4, 871)], with mutations being the most common alteration [38.6% (34/88)], followed by fusions [30.7% (27/88), including a novel SQSTM1-RET] and amplifications [25% (22/88)]. Most patients had coexisting aberrations in addition to RET anomalies [81.8% (72/88)], with the most common being in TP53-associated genes [59.1% (52/88)], cell cycle-associated genes [39.8% (35/88)], the PI3K signaling pathway [30.7% (27/88)], MAPK effectors [22.7% (20/88)], or other tyrosine kinase families [21.6% (19/88)]. RET fusions were mutually exclusive with MAPK signaling pathway alterations. All 72 patients harboring coaberrations had distinct genomic portfolios, and most [98.6% (71/72)] had potentially targetable coaberrations with either an FDA-approved or an investigational agent. Two cases with lung (KIF5B-RET) and medullary thyroid carcinoma (RET M918T) that responded to a vandetanib (multikinase RET inhibitor) containing regimen are shown.Conclusions:RET aberrations were seen in 1.8% of diverse cancers, with most cases harboring actionable, albeit distinct, coexisting alterations. The current report suggests that optimal targeting of patients with RET anomalies will require customized combination strategies. Clin Cancer Res; 23(8); 1988-97. (c)2016 AACR. PMID- 27683184 TI - Ultrasound for the rheumatologist - Subcutaneous Sarcoidosis. PMID- 27683182 TI - A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer. AB - Purpose: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride.Experimental Design: Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose dutasteride (3.5 mg daily) was added. Patients continued therapy until study withdrawal or radiographic progression. Repeat metastasis biopsy was obtained at progression. The primary endpoint was to assess mechanisms of resistance. Serum hormone and abiraterone levels were assessed. Tissue was assessed for androgen receptor (AR) and AR splice variant-7 (ARV7) expression.Results: Forty patients were enrolled. Sixty percent (n = 24) achieved a >=50% reduction in prostate-specific antigen (PSA). The median time to radiographic progression was 11 months. Nearly all baseline (n = 29 of 31) and posttreatment (n = 16 of 16) tumors tested for AR nuclear expression were positive. Of those tested, ARV7 expression was present in 48% (n = 10 of 21) of baseline and 42% (n = 5 of 12) of treatment discontinuation specimens. Compared with patients with higher serum abiraterone levels at treatment discontinuation, patients with lower levels had higher circulating androgens.Conclusions: Despite increased androgen synthesis inhibition, we demonstrate that tumor AR axis remains important in disease progression. We highlight that abiraterone metabolism and pharmacokinetics may play a role in resistance. The noncomparative design limits conclusions on the efficacy of dual therapy with abiraterone and dutasteride, but the results support development of further multifaceted approaches toward AR inhibition. Clin Cancer Res; 23(4); 935 45. (c)2016 AACR. PMID- 27683185 TI - Association Between Single Gene Polymorphisms and Bone Biomarkers and Response to Calcium and Vitamin D Supplementation in Young Adults Undergoing Military Training. AB - Initial military training (IMT) is associated with increased stress fracture risk. In prior studies, supplemental calcium (Ca) and vitamin D provided daily throughout IMT reduced stress fracture incidence, suppressed parathyroid hormone (PTH), and improved measures of bone health compared with placebo. Data were analyzed from a randomized, double-blind, placebo-controlled trial to determine whether single-nucleotide polymorphisms (SNPs) in Ca and vitamin D-related genes were associated with circulating biomarkers of bone metabolism in young adults entering IMT, and whether responses to Ca and vitamin D supplementation were modulated by genotype. Associations between SNPs, including vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-alpha-hydroxylase (CYP27B1), and circulating biomarkers were measured in fasting blood samples from volunteers (n = 748) starting IMT. Volunteers were block randomized by race and sex to receive Ca (2000 mg) and vitamin D (1000 IU) or placebo daily throughout Army or Air Force IMT (7 to 9 weeks). Total Ca and vitamin D intakes were calculated as the sum of supplemental intake based on intervention compliance and dietary intake. Relationships between SNPs, Ca, and vitamin D intake tertile and change in biomarkers were evaluated in trial completers (n = 391). At baseline, the minor allele of a DBP SNP (rs7041) was positively associated with both 25OHD (B = 4.46, p = 1.97E-10) and 1,25(OH)2 D3 (B = 9.63, p < 0.001). Combined genetic risk score (GRS) for this SNP and a second SNP in the VDR gene (rs1544410) was inversely associated with baseline 25OHD (r = -0.28, p < 0.001) and response to Ca and vitamin D intake differed by GRS (p < 0.05). In addition, presence of the minor allele of a second VDR SNP (rs2228570) was associated with lower P1NP (B = -4.83, p = 0.04) and osteocalcin (B = -0.59, p = 0.03). These data suggest that VDR and DBP SNPs are associated with 25OHD status and bone turnover and those with the highest GRS require the greatest vitamin D intake to improve 25OHD during IMT. (c) 2016 American Society for Bone and Mineral Research. PMID- 27683186 TI - Combined Influence of Genetic Polymorphism and DNA Methylation on ABCB1 Expression and Function in Healthy Chinese Males. AB - BACKGROUND AND OBJECTIVES: It is well known that the expression and function of ATP-binding cassette transporter B1 (ABCB1) show high interindividual variability, but the reasons have not yet been fully elucidated. In this study, combined influence of genetic polymorphism and DNA methylation on ABCB1 mRNA expression and digoxin pharmacokinetics in healthy Chinese males was analyzed. METHODS: A total of 93 subjects who were homozygous for the ABCB1 1236-2677-3435 TTT or CGC haplotype were enrolled in this study. DNA methylation status of the ABCB1 promoter and ABCB1 mRNA expression level in exfoliated intestinal epithelial cells were analyzed using bisulfite sequencing PCR and real-time PCR. The pharmacokinetics of digoxin in subjects were investigated after administration of a single oral dose of digoxin 0.5 mg. RESULTS: The DNA methylation levels of ABCB1 promoter showed no significant difference between TTT/TTT and CGC/CGC carriers (P = 0.54). Subjects with TTT/TTT haplotype pair and high methylation status (TTT/TTT-HM) showed a significantly lower ABCB1 mRNA level compared to other subjects. Compared with TTT/TTT-HM subgroup, the area under the plasma concentration-time curve from time zero to 72 h (AUC0-72) of digoxin was decreased by 26.9 %, the maximum plasma concentration (C max) was decreased by 25 % and the apparent oral clearance (CL/F) was increased by 21.2 % in CGC/CGC-LM subgroup. The values of time to maximum concentration (t max) and terminal elimination half-life (t 1/2) showed no significant difference. CONCLUSIONS: Both genetic polymorphism and DNA methylation variation should be taken into consideration to explain the interindividual variability in ABCB1 expression and function more clearly. PMID- 27683188 TI - Sonographic depiction of non-palpable uterine papillary serous carcinoma metastasis embedded within the abdominal wall. PMID- 27683189 TI - Acquiring and processing ultrafast biomolecular 2D NMR experiments using a referenced-based correction. AB - Thanks to their special spatiotemporal encoding/decoding scheme, ultrafast (UF) NMR sequences can deliver arbitrary 2D spectra following a single excitation. Regardless of their nature, these sequences have in common their tracing of a path in the [Formula: see text]-[Formula: see text] plane, that will deliver the spectrum being sought after a 1D Fourier transformation versus [Formula: see text]. This need to simultaneously digitize two domains, tends to impose bandwidth limitations along all spectral axes. Along the [Formula: see text]/[Formula: see text] dimension this problem is exacerbated by the fact that odd and even time points are not equispaced, and by additional artifacts such as time shifts between time points sampled while under the action of positive and negative decoding gradients. As a result, odd and even [Formula: see text] points are typically Fourier transformed separately, halving the potential spectral width along this dimension. While this halving of the [Formula: see text] span can be overcome by an interlaced Fourier transform, this post-processing is seldom used because of its sensitivity to hardware inaccuracies requiring even finer corrections of the even/odd [Formula: see text] data points. These corrections have so far been done manually, but are challenging to implement when dealing with low signal-to-noise ratio signals like those associated with biomolecular NMR experiments. This study introduces an algorithm for an automatic correction of all even/odd ultrafast NMR inconsistencies, based on the acquisition of a reference scan on the solvent. This algorithm was verified experimentally using an [Formula: see text]-[Formula: see text] UF-HSQC variant on ubiquitin at 600 MHz. Features of this method as well as of the interlaced Fourier transformation in general, are discussed. PMID- 27683190 TI - Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density. AB - Desferrioxamine (DFO) is a clinically approved, high affinity iron chelator used for the treatment of iron overload. Due to its short half-life and toxicity, DFO is administered for 8-12 h per day, 5-7 d per week. In this manuscript, the influence of molecular properties of hyperbranched polyglycerol (HPG)-DFO conjugates on their iron binding by isothermal titration calorimetry, iron removal efficiency from ferritin in presence and absence of a low molecular weight (MW) iron chelator, and protection against iron mediated oxidation of proteins is reported. The iron binding properties of HPG-DFO are slightly altered with size and DFO density of conjugates. The lower MW conjugate shows greater iron removal efficiency at room temperature, however, the efficacy of high MW conjugates increases at physiological temperature. The iron removal from ferritin by HPG-DFO conjugates increases significantly in presence of a low MW chelator, suggesting the potential of combination therapy. The molecular properties of the polymer scaffold also have influence on the prevention of iron mediated oxidation of proteins by the conjugates. The results therefore help to define the iron binding thermodynamics of HPG-DFO and their dependence on MW, and can be extended to improve the general understanding of polymeric chelator-iron interactions in situ. PMID- 27683187 TI - Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects. AB - Curcumin is a natural product with many interesting pharmacological properties. However, these are offset by the particularly poor biopharmaceutical properties. The oral bioavailability of curcumin in humans is very low, mainly due to low solubility, poor stability, and extensive metabolism. This has led to multiple approaches to improve bioavailability, including administration of curcumin with metabolism inhibitors, formulation into nanoparticles, modification of the curcumin structure, and development of curcumin prodrugs. In this paper, we focus on the pharmacokinetic outcomes of these approaches. Pharmacokinetic parameters of curcumin after release from prodrugs are dependent on the linker between curcumin and the promoiety, and the release itself may depend on the physiological and enzymatic environment at the site of cleavage. This is an area in which more data are required for rational design of improved linkers. Cytotoxicity of curcumin prodrugs seems to correlate well with cellular uptake in vitro, but the in vivo relevance is uncertain. We conclude that improved experimental and theoretical models of absorption of curcumin prodrugs, development of accurate analytical methods for simultaneous measurement of plasma levels of prodrug and released curcumin, and acquisition of more pharmacokinetic data in animal models for dose prediction in humans are required to facilitate movement of curcumin prodrugs into clinical trials. PMID- 27683192 TI - Home- or self-tonometry to the follow-up of intraocular pressure in glaucoma. PMID- 27683191 TI - The prognosis of liver resection for patients with four or more colorectal liver metastases has not improved in the era of modern chemotherapy. AB - BACKGROUND AND OBJECTIVES: The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for >=4 CRLM. METHODS: Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with >=4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan. RESULTS: There were 50 and 144 patients with >=4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of >=20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of >=100 U/ml (P = 0.018), and a primary colorectal cancer N factor of >=N2 (P = 0.023). CONCLUSIONS: The prognosis of patients with >=4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959 965. (c) 2016 Wiley Periodicals, Inc. PMID- 27683193 TI - Gender and socio-economic inequalities in health and living conditions among co resident informal caregivers: a nationwide survey in Spain. AB - AIMS: To explore the associations between social determinants, caregiver's network support, burden of care and their consequences in health and living conditions of informal caregivers. BACKGROUND: The socio-demographic trends regarding population ageing and changes in family models trigger an increased demand for care. DESIGN: Cross-sectional study based on the 2008 edition of the National Disability, Independence and Dependency Situations Survey (DIDSS-2008) conducted by the National Statistics Institute in Spain. METHODS: Analyses focused on persons identified as primary caregivers who co-reside with the dependent person. The associations between social determinants of caregivers, burden of care, support network and problems attributed to informal care (impaired health, depression, professional, economic and personal issues) were estimated by fitting robust Poisson regression models. Analyses were conducted separately for women and men. RESULTS: The study sample included 6923 caregivers, 73% of women and 27% of men. Gender and socio-economic inequalities were found in assumption of responsibilities and burden of caring for dependents, which tend to fall more on women and persons of lower socio-economic level, who in turn have less access to formal support. These aspects translate into a higher prevalence of health, professional, economic and personal problems. CONCLUSIONS: The study highlights gender and socio-economic inequalities in informal caregiving and its negative consequences. These findings may be useful in the design of policies and support programmes targeting the most affected groups of informal caregivers. PMID- 27683194 TI - Comparison of early osseointegration of SLA(r) and SLActive(r) implants in maxillary sinus augmentation: a pilot study. AB - OBJECTIVE: To assess the impact of a hydrophilic implant surface (SLActive(r) ) placed into augmented maxillary sinuses on bone-to-implant contact (BIC) and surrounding tissue composition when compared to a hydrophobic surface (SLA(r) ). MATERIAL AND METHODS: Four sheep underwent bilateral sinus augmentation. Each sinus received anorganic bovine bone mineral + autogenous bone (ABBM + AB). Sixteen implants were subsequently placed 12 weeks postgrafting with each sinus receiving a control (SLA(r) ) and test implant (SLActive(r) ). Two animals were sacrificed at 2 weeks and another two animals were sacrificed at 4 weeks postimplantation. The eight sinuses and 16 implants were processed for histomorphometry, which assessed bone-to-implant contact (%BIC) and tissue elements (woven bone - WB, lamellar bone - LB, soft tissue - ST) in the interthread region of implants within the augmented sinus. RESULTS: There was a statistically significant increase in %BIC at week 4 compared to the week 2 animals in both test (P < 0.005) and control (P < 0.005) groups. There was a statistically significant greater %BIC around test implants when compared to control implants in both week 2 (P < 0.05) and week 4 animals (P < 0.05). Greater %WB (11.17% +/-6.82) and %LB (11.06% +/-3.67) were seen in the test implants when compared to the control implants independent of time. This was only statistically significant for %LB (P < 0.05). A statistically significant reduction of 16.78% (+/-6.19) in %ST was noted in test implants when compared to control implants (P < 0.05) independent of time. CONCLUSION: Both time and the use of hydrophilic implant surface had a positive impact on %BIC around implants placed into augmented maxillary sinuses. Hydrophilic implant surfaces also had a positive impact on surrounding tissue composition. Larger trials are needed to better assess and detect differences between these two surfaces in augmented maxillary sinuses. PMID- 27683195 TI - First evidence of Smith-Magenis syndrome in mother and daughter due to a novel RAI mutation. AB - Smith-Magenis syndrome (SMS) is a complex genetic disorder caused by interstitial 17p11.2 deletions encompassing multiple genes, including the retinoic acid induced 1 gene-RAI1-or mutations in RAI1 itself. The clinical spectrum includes developmental delay, cognitive impairment, and behavioral abnormalities, with distinctive physical features that become more evident with age. No patients have been reported to have had offspring. We here describe a girl with developmental delay, mainly compromising the speech area, and her mother with mild intellectual disabilities and minor dysmorphic features. Both had sleep disturbance and attention deficit disorder, but no other atypical behaviors have been reported. In both, CGH-array analysis detected a 15q13.3 interstitial duplication, encompassing CHRNA7. However, the same duplication has been observed in several, apparently healthy, maternal relatives. We, thus, performed a whole exome sequencing analysis, which detected a frameshift mutation in RAI1, de novo in the mother, and transmitted to her daughter. No other family members carried this mutation. This is the first report of an SMS patient having offspring. Our experience confirms the importance of searching for alternative causative genetic mechanisms in case of confounding/inconclusive findings such as a CGH-array result of uncertain significance. (c) 2016 Wiley Periodicals, Inc. PMID- 27683196 TI - Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options. AB - BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) represents the most severe form of gastrointestinal dysmotility with debilitating and potentially lethal consequences. Symptoms can be non-specific, and result in this condition being diagnosed incorrectly or too late with consequences for morbidity and even mortality. PURPOSE: The present article aims to provide pediatric and adult gastroenterologists with an up to date review about clinical features, diagnosis and therapeutic options for CIPO. Although pediatric and adult CIPO share many clinical aspects distinctive features can be identified. There is no single diagnostic test or pathognomonic finding of CIPO, thus a stepwise approach including radiology, endoscopy, laboratory, manometry, and histopathology should be considered in the diagnostic work-up. Treatment of patients with CIPO is challenging and requires a multidisciplinary effort with participation of appropriately experienced gastroenterologists, pathologists, dieticians, surgeons, psychologists, and other subspecialists based on the presence of comorbidities. Current treatment options invariably involve surgery and specialized nutritional support, especially in children. Medical therapies are mainly aimed to avoid complications such as sepsis or intestinal bacterial overgrowth and, where possible, restore intestinal propulsion. More efficacious therapeutic options are eagerly awaited for such difficult patients. PMID- 27683197 TI - Observational evidence that maladaptive gene flow reduces patch occupancy in a wild insect metapopulation. AB - Theory predicts that dispersal throughout metapopulations has a variety of consequences for the abundance and distribution of species. Immigration is predicted to increase abundance and habitat patch occupancy, but gene flow can have both positive and negative demographic consequences. Here, we address the eco-evolutionary effects of dispersal in a wild metapopulation of the stick insect Timema cristinae, which exhibits variable degrees of local adaptation throughout a heterogeneous habitat patch network of two host-plant species. To disentangle the ecological and evolutionary contributions of dispersal to habitat patch occupancy and abundance, we contrasted the effects of connectivity to populations inhabiting conspecific host plants and those inhabiting the alternate host plant. Both types of connectivity should increase patch occupancy and abundance through increased immigration and sharing of beneficial alleles through gene flow. However, connectivity to populations inhabiting the alternate host plant species may uniquely cause maladaptive gene flow that counters the positive demographic effects of immigration. Supporting these predictions, we find the relationship between patch occupancy and alternate-host connectivity to be significantly smaller in slope than the relationship between patch occupancy and conspecific-host connectivity. Our findings illustrate the ecological and evolutionary roles of dispersal in driving the distribution and abundance of species. PMID- 27683198 TI - Workload pressures are leading to unsafe hospital discharges, say MPs. PMID- 27683199 TI - A Novel Colonial Ciliate Zoothamnium ignavum sp. nov. (Ciliophora, Oligohymenophorea) and Its Ectosymbiont Candidatus Navis piranensis gen. nov., sp. nov. from Shallow-Water Wood Falls. AB - Symbioses between ciliate hosts and prokaryote or unicellular eukaryote symbionts are widespread. Here, we report on a novel ciliate species within the genus Zoothamnium Bory de St. Vincent, 1824, isolated from shallow-water sunken wood in the North Adriatic Sea (Mediterranean Sea), proposed as Zoothamnium ignavum sp. nov. We found this ciliate species to be associated with a novel genus of bacteria, here proposed as "Candidatus Navis piranensis" gen. nov., sp. nov. The descriptions of host and symbiont species are based on morphological and ultrastructural studies, the SSU rRNA sequences, and in situ hybridization with symbiont-specific probes. The host is characterized by alternate microzooids on alternate branches arising from a long, common stalk with an adhesive disc. Three different types of zooids are present: microzooids with a bulgy oral side, roundish to ellipsoid macrozooids, and terminal zooids ellipsoid when dividing or bulgy when undividing. The oral ciliature of the microzooids runs 11/4 turns in a clockwise direction around the peristomial disc when viewed from inside the cell and runs into the infundibulum, where it makes another 3/4 turn. The ciliature consists of a paroral membrane (haplokinety), three adoral membranelles (polykineties), and one stomatogenic kinety (germinal kinety). One circular row of barren kinetosomes is present aborally (trochal band). Phylogenetic analyses placed Z. ignavum sp. nov. within the clade II of the polyphyletic family Zoothamniidae (Oligohymenophorea). The ectosymbiont was found to occur in two different morphotypes, as rods with pointed ends and coccoid rods. It forms a monophyletic group with two uncultured Gammaproteobacteria within an unclassified group of Gammaproteobacteria, and is only distantly related to the ectosymbiont of the closely related peritrich Z. niveum (Hemprich and Ehrenberg, 1831) Ehrenberg, 1838. PMID- 27683200 TI - A Qualitative Approach to the Intersection of Sexual, Ethnic, and Gender Identities. AB - In this paper we report on a new qualitative instrument designed to study the intersection of identities related to sexuality and race/ethnicity, and how people who hold those identities interact with social contexts. Researchers often resort to using separate measures to assess race/ethnicity, sexual orientation, and other target identities. But this approach can miss elements of a self-system that stem from the intersection of identities, the interactions between identities and social contexts, related shifts in identity over time, and related changes in the prominence and valence of identities. Using a small sub-sample, we demonstrate how our instrument can help researchers overcome these limitations. Our instrument was also designed for economy in administration and analysis, so that it could be used as a qualitative complement in large survey research. PMID- 27683201 TI - [Rare combination of causes in thoracic inlet syndrome]. PMID- 27683202 TI - Evolving Health Expenditure Landscape of the BRICS Nations and Projections to 2025. AB - Global health spending share of low/middle income countries continues its long term growth. BRICS nations remain to be major drivers of such change since 1990s. Governmental, private and out-of-pocket health expenditures were analyzed based on WHO sources. Medium-term projections of national health spending to 2025 were provided based on macroeconomic budgetary excess growth model. In terms of per capita spending Russia was highest in 2013. India's health expenditure did not match overall economic growth and fell to slightly less than 4% of GDP. Up to 2025 China will achieve highest excess growth rate of 2% and increase its GDP% spent on health care from 5.4% in 2012 to 6.6% in 2025. Russia's spending will remain highest among BRICS in absolute per capita terms reaching net gain from $1523 PPP in 2012 to $2214 PPP in 2025. In spite of BRICS' diversity, all countries were able to significantly increase their investments in health care. The major setback was bold rise in out-of-pocket spending. Most of BRICS' growing share of global medical spending was heavily attributable to the overachievement of People's Republic of China. Such trend is highly likely to continue beyond 2025. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27683204 TI - Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy. AB - OBJECTIVES: Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. METHODS: We conducted a prospective cohort study of 122 HSV 2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. RESULTS: At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. CONCLUSION: Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. PMID- 27683203 TI - The Structure of Treponema pallidum Tp0751 (Pallilysin) Reveals a Non-canonical Lipocalin Fold That Mediates Adhesion to Extracellular Matrix Components and Interactions with Host Cells. AB - Syphilis is a chronic disease caused by the bacterium Treponema pallidum subsp. pallidum. Treponema pallidum disseminates widely throughout the host and extravasates from the vasculature, a process that is at least partially dependent upon the ability of T. pallidum to interact with host extracellular matrix (ECM) components. Defining the molecular basis for the interaction between T. pallidum and the host is complicated by the intractability of T. pallidum to in vitro culturing and genetic manipulation. Correspondingly, few T. pallidum proteins have been identified that interact directly with host components. Of these, Tp0751 (also known as pallilysin) displays a propensity to interact with the ECM, although the underlying mechanism of these interactions remains unknown. Towards establishing the molecular mechanism of Tp0751-host ECM attachment, we first determined the crystal structure of Tp0751 to a resolution of 2.15 A using selenomethionine phasing. Structural analysis revealed an eight-stranded beta barrel with a profile of short conserved regions consistent with a non-canonical lipocalin fold. Using a library of native and scrambled peptides representing the full Tp0751 sequence, we next identified a subset of peptides that showed statistically significant and dose-dependent interactions with the ECM components fibrinogen, fibronectin, collagen I, and collagen IV. Intriguingly, each ECM interacting peptide mapped to the lipocalin domain. To assess the potential of these ECM-coordinating peptides to inhibit adhesion of bacteria to host cells, we engineered an adherence-deficient strain of the spirochete Borrelia burgdorferi to heterologously express Tp0751. This engineered strain displayed Tp0751 on its surface and exhibited a Tp0751-dependent gain-of-function in adhering to human umbilical vein endothelial cells that was inhibited in the presence of one of the ECM-interacting peptides (p10). Overall, these data provide the first structural insight into the mechanisms of Tp0751-host interactions, which are dependent on the protein's lipocalin fold. PMID- 27683207 TI - RETRACTED ARTICLE: Genetic Structure and Diversity Analysis Revealed by AFLP Markers on Different Glycyrrhiza glabra L. an Endangered Medicinal Species from South of Iran and Implications for Conservation. PMID- 27683206 TI - Subconjunctival gentamicin-induced macular toxicity following sutureless 25-gauge vitrectomy. PMID- 27683205 TI - Uncoupling associations of risk alleles with endophenotypes and phenotypes: insights from the ApoB locus and heart-related traits. AB - Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogeneous, age-related traits driven by the elusive role of evolution in their properties. We analyzed in detail the associations of rs693 and rs562338 polymorphisms representing the Apolipoprotein B locus with endophenotypes (total cholesterol [TC] and high-density lipoprotein cholesterol) and phenotypes (myocardial infarction [MI] and survival) in four large-scale studies, which include 20 748 individuals with 2357 MI events. We showed that a strong, robust predisposition of rs693 and rs562338 to TC (beta = 0.72, P = 7.7 * 10-30 for rs693 and beta = -1.08, P = 9.8 * 10-42 for rs562338) is not translated into a predisposition to MI and survival. The rs693_A allele influences risks of MI and mortality after MI additively with lipids. This allele shows antagonistic effects-protecting against MI risks (beta = -0.18, P = 1.1 * 10-5 ) or increasing MI risks (beta = 0.15, P = 2.8 * 10-3 ) and mortality after MI, in different populations. Paradoxically, increased TC concentrations can be protective against MI for the rs693_A allele carriers. Our results uncouple the influences of the same alleles on endophenotypes and phenotypes despite potential causal relationships among the latter. Our strategy reveals virtually genomewide significance for the associations of rs693 with MI (P = 5.5 * 10-8 ) that is contrasted with a weak estimate following the traditional, sample-size-centered GWAS strategy (P = 0.16) in the same sample. These results caution against the use of the traditional GWAS strategy for gaining profound insights into genetic predisposition to healthspan and lifespan. PMID- 27683208 TI - The full blood count as a biomarker of outcome and toxicity in ipilimumab-treated cutaneous metastatic melanoma. AB - Ipilimumab produces durable responses in some metastatic melanoma patients. Neutrophil, platelet, and eosinophil to lymphocyte ratios (NLR, PLR, and ELR) may be associated with the immune response in cancer thereby acting as biomarkers of toxicity and efficacy in ipilimumab-treated patients. Data were collected on clinical characteristics and lactate dehydrogenase (LDH), NLR, PLR, and ELR at baseline, post cycle 2 and at the end of treatment for 183 patients treated with ipilimumab between 2008 and 2015 at the Princess Margaret Cancer Centre. Associations between clinical characteristics, LDH, NLR, PLR, and ELR with toxicity or survival outcomes of progression-free (PFS) and overall survival (OS) were assessed using univariable and multivariable analysis. Prognostic models of outcome at each time point were determined. Of the 183 patients included, the median age was 58, 85% had M1c disease, 58% were performance status 1, and 64% received ipilimumab as second line therapy. Median follow up was 7.5 months (range: 0.3-49.5), median PFS was 2.8 months (95% confidence intervals (CI): 2.8 3.2), and median OS was 9.6 months (95% CI: 7.9-13.2). Prognostic factors for OS by multivariable analysis were LDH and NLR at all-time points. Prognostic models using LDH (* 2 upper limit of normal) and NLR 4) differentiated patients into high, moderate, and low risk of death prior to or on ipilimumab treatment (P < 0.0001 for each model). No factors were associated with toxicity. Prognostic models based on NLR and LDH values at baseline and on treatment differentiate patients into good, intermediate, and poor prognostic groups and may be relevant in patient management. PMID- 27683209 TI - The association between mammographic calcifications and breast cancer prognostic factors in a population-based registry cohort. AB - BACKGROUND: Mammographic calcifications can be a marker of malignancy, but their association with prognosis is less well established. In the current study, the authors examined the relationship between calcifications and breast cancer prognostic factors in the population-based Carolina Mammography Registry. METHODS: The current study included 8472 invasive breast cancers diagnosed in the Carolina Mammography Registry between 1996 and 2011 for which information regarding calcifications occurring within 2 years of diagnosis was reported. Calcification-specific Breast Imaging Reporting and Data System (BI-RADS) assessments were reported prospectively by a radiologist. Tumor characteristic data were obtained from the North Carolina Central Cancer Registry and/or pathology reports. Multivariable-adjusted associations between the presence of calcifications in the breast affected by cancer and tumor characteristics were estimated using logistic regression. Statistical tests were 2-sided. RESULTS: The presence of calcifications was found to be positively associated with tumors that were high grade (vs low grade: odds ratio [OR], 1.43; 95% confidence interval [95% CI], 1.10-1.88) or had an in situ component (vs without: OR, 2.15; 95% CI, 1.81-2.55). Calcifications were found to be inversely associated with hormone receptor-negative status (vs positive status: OR, 0.73; 95% CI, 0.57-0.93), size >35 mm (vs <=8 mm: OR, 0.47; 95% CI, 0.37-0.61), and lobular tumors (vs ductal: OR, 0.39; 95% CI, 0.22-0.69). The association between the presence of calcifications and an in situ component was limited to BI-RADS category 4 and 5 calcifications and was absent for BI-RADS category 2 or 3 calcifications (P for heterogeneity <.01). The association with tumor size was found to be strongest for BI-RADS categories 3 and 4 (P for heterogeneity <.01). CONCLUSIONS: Calcifications were found to be associated with both unfavorable (high grade) and favorable (small size, hormone receptor positivity) prognostic factors. Detailed analysis of the biological features of calcifications is necessary to understand the mechanisms driving these associations. Cancer 2017;123:219-227. (c) 2016 American Cancer Society. PMID- 27683210 TI - A novel self-cleavable tag Zbasic-?I-CM and its application in the soluble expression of recombinant human interleukin-15 in Escherichia coli. AB - Soluble expression of recombinant therapeutic proteins in Escherichia coli (E. coli) has been a challenging task in biopharmaceutical development. In this study, a novel self-cleavable tag Zbasic-intein has been constructed for the soluble expression and purification of a recombinant cytokine, human interleukin 15 (IL-15). We screened several solubilizing tags fused with the self-cleavable Mycobacterium tuberculosis recA mini-intein ?I-CM and demonstrated that Zbasic tag can significantly improve the solubility of the product with correspondent to the intein activity. The fusion protein "Zbasic-?I-CM-IL-15" was expressed with high solubility and easily enriched by the cost-effective cation-exchange chromatography. The self-cleavage of the fusion tag Zbasic-?I-CM was then induced by a pH shift, with an activation energy of 7.48 kcal/mol. The mature IL-15 with natural N-terminus was released and further purified by hydrophobic interaction and anion-exchange chromatography. High-resolution reverse-phase high-performance liquid chromatography and mass spectrometry analysis confirmed that the product was of high purity and correct mass. With a CTLL-2 cell proliferation-based assay, the EC50 was evaluated to be of about 0.126 ng/mL, similar to the product in clinical trials. By avoiding the time-consuming denaturing-refolding steps in previously reported processes, the current method is efficient and cost effective. The novel tag Zbasic-?I-CM can be potentially applied to large-scale manufacturing of recombinant human cytokines as well as other mammalian-sourced proteins in E. coli. PMID- 27683211 TI - Characterization and genome sequencing of a Citrobacter freundii phage CfP1 harboring a lysin active against multidrug-resistant isolates. AB - Citrobacter spp., although frequently ignored, is emerging as an important nosocomial bacterium able to cause various superficial and systemic life threatening infections. Considered to be hard-to-treat bacterium due to its pattern of high antibiotic resistance, it is important to develop effective measures for early and efficient therapy. In this study, the first myovirus (vB_CfrM_CfP1) lytic for Citrobacter freundii was microbiologically and genomically characterized. Its morphology, activity spectrum, burst size, and biophysical stability spectrum were determined. CfP1 specifically infects C. freundii, has broad host range (>85 %; 21 strains tested), a burst size of 45 PFU/cell, and is very stable under different temperatures (-20 to 50 degrees C) and pH (3 to 11) values. CfP1 demonstrated to be highly virulent against multidrug-resistant clinical isolates up to 12 antibiotics, including penicillins, cephalosporins, carbapenems, and fluroquinoles. Genomically, CfP1 has a dsDNA molecule with 180,219 bp with average GC content of 43.1 % and codes for 273 CDSs. The genome architecture is organized into function-specific gene clusters typical for tailed phages, sharing 46 to 94 % nucleotide identity to other Citrobacter phages. The lysin gene encoding a predicted D-Ala-D-Ala carboxypeptidase was also cloned and expressed in Escherichia coli and its activity evaluated in terms of pH, ionic strength, and temperature. The lysine optimum activity was reached at 20 mM HEPES, pH 7 at 37 degrees C, and was able to significantly reduce all C. freundii (>2 logs) as well as Citrobacter koseri (>4 logs) strains tested. Interestingly, the antimicrobial activity of this enzyme was performed without the need of pretreatment with outer membrane destabilizing agents. These results indicate that CfP1 lysin is a good candidate to control problematic Citrobacter infections, for which current antibiotics are no longer effective. PMID- 27683212 TI - Bacterial communities involved in sulfur transformations in wastewater treatment plants. AB - The main sulfate-reducing (SRB) and sulfur-oxidizing bacteria (SOB) in six wastewater treatment plants (WWTPs) located at southern Brazil were described based on high-throughput sequencing of the 16S rDNA. Specific taxa of SRB and SOB were correlated with some abiotic factors, such as the source of the wastewater, oxygen content, sample type, and physical chemical attributes of these WWTPs. When the 22 families of SRB and SOB were clustered together, the samples presented a striking distribution, demonstrating grouping patterns according to the sample type. For SOB, the most abundant families were Spirochaetaceae, Chromatiaceae, Helicobacteriaceae, Rhodospirillaceae, and Neisseriaceae, whereas, for SRB, were Syntrophaceae, Desulfobacteraceae, Nitrospiraceae, and Desulfovibriaceae. The structure and composition of the major families related to the sulfur cycle were also influenced by six chemical attributes (sulfur, potassium, zinc, manganese, phosphorus, and nitrogen). Sulfur was the chemical attribute that most influenced the variation of bacterial communities in the WWTPs (lambda = 0.14, p = 0.008). The OTUs affiliated to Syntrophus showed the highest response to the increase of total sulfur. All these findings can contribute to improve the understanding in relation to the sulfur-oxidizing and sulfate-reducing communities in WWTPs aiming to reduce H2S emissions. PMID- 27683213 TI - Number of Unfavorable Intermediate-Risk Factors Predicts Pathologic Upstaging and Prostate Cancer-Specific Mortality Following Radical Prostatectomy: Results From the SEARCH Database. AB - BACKGROUND: To validate and further improve the stratification of intermediate risk prostate cancer into favorable and unfavorable subgroups for patients undergoing radical prostatectomy. MATERIALS AND METHODS: The SEARCH database was queried for IR patients undergoing radical prostatectomy without adjuvant radiotherapy. UIR disease was defined any patient with at least one unfavorable risk factor (URF), including primary Gleason pattern 4, 50% of more biopsy cores containing cancer, or multiple National Comprehensive Cancer Network IR factors. RESULTS: One thousand five hundred eighty-six patients with IR prostate cancer comprised the study cohort. Median follow-up was 62 months. Patients classified as UIR were significantly more likely to have pathologic high-risk features, such as Gleason score 8 - 10, pT3-4 disease, or lymph node metastases, than FIR patients (P < 0.001). Furthermore, UIR patients had significantly higher rates of PSA-relapse (PSA, hazard ratio [HR] = 1.89, P < 0.001) and distant metastasis (DM, HR = 2.92, P = 0.001), but no difference in prostate cancer-specific mortality (PCSM) or all-cause mortality in multivariable analysis. On secondary analysis, patients with >=2 URF had significantly worse PSA-RFS, DM, and PCSM than those with 0 or 1 URF. Moreover, 40% of patients with >=2 URF had high-risk pathologic features. CONCLUSIONS: Patients with UIR prostate cancer are at increased risk of PSA relapse, DM, and pathologic upstaging following prostatectomy. However, increased risk of PCSM was only detected in those with >=2 URF. This suggests that further refinement of the UIR subgroup may improve risk stratification. Prostate Prostate 77:154-163, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27683214 TI - Persistency, medication prescribing patterns, and medical resource use associated with multiple sclerosis patients receiving oral disease-modifying therapies: a retrospective medical record review. AB - BACKGROUND: In the US, the approved multiple sclerosis (MS) oral disease modifying therapies (ODMTs) are fingolimod (FTY), teriflunomide (TFN), and dimethyl fumarate (DMF). FTY and TFN are recommended with once-daily doses with no up-titration, whereas DMF treatment is recommended twice-daily (BID) and is initiated with a 7-day starter dose of 120 mg BID before up-titration to the maintenance dose of 240 mg BID. Limited information exists regarding real-world ODMT prescribing patterns to aid physician/patient decision-making. METHODS: Eligible patients for this retrospective medical record review were >=18 years, had one visit related to ODMT initiation (index visit), and >=1 visit within 12 months before and after the index visit. Primary objectives were to assess post index ODMT persistency (i.e., discontinuation), prescribing patterns (medication switching, dose up-titrations, dose reduction, re-starts, and add-ons) and medical resource utilization (office-visits, MRI procedures, and mobility indicators) at distinct time windows of 3, 6, 9, and 12 months. Chi-square or Wilcoxon Rank Sum tests were used for 3-way ODMT group comparisons. RESULTS: Medical records of 293 MS-diagnosed patients using ODMTs were abstracted from 19 US-based neurology clinics between December 31, 2010 and June 30, 2014 (FTY: 101; DMF: 133; TFN: 59). Persistency rates among ODMT groups were similar. MS-related medication switching, dose reduction, re-starts, and add-ons were infrequently observed and were similar across ODMT groups. Of DMF patients with a confirmed starting dose of 120 mg BID with >=12 months follow-up (n = 26), the percentage who were prescribed dose up-titrations to the recommended maintenance DMF dose was 23.1 % at 1-3 months, 26.9 % at 4-6 months, 42.3 % at 7-9 months, and 0 % at 10-12 months. There were no significant differences at any time window among the ODMT groups in the number of office visits or percent of patients receiving MRIs. Mobility indicator patterns (proportion of patients with abnormal gait, wheelchair use, etc.) were consistent over time. CONCLUSIONS: There was no difference in persistency, prescribing patterns (medication switching, dose reduction, re-starts, and add-ons) or medical resource utilization (office visits, MRI procedures, and mobility indicators) among the ODMTs. However, in a small sub-group of patients, delays of up to 9 months in DMF dose-up titration to the recommended maintenance dose were observed. PMID- 27683215 TI - Limited Clinical Significance of Dimeric Form of Pyruvate Kinase as a Diagnostic and Prognostic Biomarker in Non-small Cell Lung Cancer. AB - Metabolism of tumor tissue differs from the normal one by the intensity of protein synthesis and glycolysis. The dimeric pyruvate kinase (PKM2) is a specific enzyme for tumor glycolysis. The aim of this study was to determine the relationship between the activity of PKM2 and the type and stage of non-small cell lung cancer (NSCLC). A second objective was to compare the expression of PKM2 with disease progression and prognosis. We studied 65 patients divided into two groups: 45 patients with lung cancer and 20 non-cancer healthy subjects taken as control. The serum activity of PKM2 was assessed spectrophotometrically. We found that PKM2 activity was greater, on average, by 136 % for adenocarcinoma and for 126 % for squamous cell carcinoma compared with that present in control subjects. The higher PKM2 activity was associated only with Stage III of cancer (p < 0.001). Sensitivity of PKM2 as a cancer marker was 79 % for adenocarcinoma and 81 % for squamous cell carcinoma and specificity was 50 % for both cancer types. We conclude that PKM2 activity is higher in patients with NSCLC than in healthy subjects. The level of PKM2 activity is associated with advanced stage of cancer. Nonetheless, low specificity of PKM2 assessment makes it of limited utility in NSCLC diagnosis or evaluation of cancer progression. PMID- 27683216 TI - Food-Web Complexity in Guaymas Basin Hydrothermal Vents and Cold Seeps. AB - In the Guaymas Basin, the presence of cold seeps and hydrothermal vents in close proximity, similar sedimentary settings and comparable depths offers a unique opportunity to assess and compare the functioning of these deep-sea chemosynthetic ecosystems. The food webs of five seep and four vent assemblages were studied using stable carbon and nitrogen isotope analyses. Although the two ecosystems shared similar potential basal sources, their food webs differed: seeps relied predominantly on methanotrophy and thiotrophy via the Calvin-Benson Bassham (CBB) cycle and vents on petroleum-derived organic matter and thiotrophy via the CBB and reductive tricarboxylic acid (rTCA) cycles. In contrast to symbiotic species, the heterotrophic fauna exhibited high trophic flexibility among assemblages, suggesting weak trophic links to the metabolic diversity of chemosynthetic primary producers. At both ecosystems, food webs did not appear to be organised through predator-prey links but rather through weak trophic relationships among co-occurring species. Examples of trophic or spatial niche differentiation highlighted the importance of species-sorting processes within chemosynthetic ecosystems. Variability in food web structure, addressed through Bayesian metrics, revealed consistent trends across ecosystems. Food-web complexity significantly decreased with increasing methane concentrations, a common proxy for the intensity of seep and vent fluid fluxes. Although high fluid fluxes have the potential to enhance primary productivity, they generate environmental constraints that may limit microbial diversity, colonisation of consumers and the structuring role of competitive interactions, leading to an overall reduction of food-web complexity and an increase in trophic redundancy. Heterogeneity provided by foundation species was identified as an additional structuring factor. According to their biological activities, foundation species may have the potential to partly release the competitive pressure within communities of low fluid-flux habitats. Finally, ecosystem functioning in vents and seeps was highly similar despite environmental differences (e.g. physico chemistry, dominant basal sources) suggesting that ecological niches are not specifically linked to the nature of fluids. This comparison of seep and vent functioning in the Guaymas basin thus provides further supports to the hypothesis of continuity among deep-sea chemosynthetic ecosystems. PMID- 27683217 TI - Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways. AB - The selection of 3? splice sites (3?ss) is an essential early step in mammalian RNA splicing reactions, but the processes involved are unknown. We have used single molecule methods to test whether the major components implicated in selection, the proteins U2AF35 and U2AF65 and the U2 snRNP, are able to recognize alternative candidate sites or are restricted to one pre-specified site. In the presence of adenosine triphosphate (ATP), all three components bind in a 1:1 stoichiometry with a 3?ss. Pre-mRNA molecules with two alternative 3?ss can be bound concurrently by two molecules of U2AF or two U2 snRNPs, so none of the components are restricted. However, concurrent occupancy inhibits splicing. Stoichiometric binding requires conditions consistent with coalescence of the 5? and 3? sites in a complex (I, initial), but if this cannot form the components show unrestricted and stochastic association. In the absence of ATP, when complex E forms, U2 snRNP association is unrestricted. However, if protein dephosphorylation is prevented, an I-like complex forms with stoichiometric association of U2 snRNPs and the U2 snRNA is base-paired to the pre-mRNA. Complex I differs from complex A in that the formation of complex A is associated with the loss of U2AF65 and 35. PMID- 27683219 TI - Rev1 is a base excision repair enzyme with 5'-deoxyribose phosphate lyase activity. AB - Rev1 is a member of the Y-family of DNA polymerases and is known for its deoxycytidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. In light of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cells treated with a base excision repair-inducing agent, we questioned whether Rev1 could also be involved in base excision repair (BER). Here, we uncovered a weak 5' deoxyribose phosphate (5'-dRP) lyase activity in mouse Rev1 and demonstrated the enzyme can mediate BER in vitro The full-length Rev1 protein and its catalytic core domain are similar in their ability to support BER in vitro The dRP lyase activity in both of these proteins was confirmed by NaBH4 reduction of the Schiff base intermediate and kinetics studies. Limited proteolysis, mass spectrometry and deletion analysis localized the dRP lyase active site to the C-terminal segment of Rev1's catalytic core domain. These results suggest that Rev1 could serve as a backup polymerase in BER and could potentially contribute to AID initiated antibody diversification through this activity. PMID- 27683222 TI - 2016 update of the PRIDE database and its related tools. PMID- 27683218 TI - Methylation at position 32 of tRNA catalyzed by TrmJ alters oxidative stress response in Pseudomonas aeruginosa. AB - Bacteria respond to environmental stresses using a variety of signaling and gene expression pathways, with translational mechanisms being the least well understood. Here, we identified a tRNA methyltransferase in Pseudomonas aeruginosa PA14, trmJ, which confers resistance to oxidative stress. Analysis of tRNA from a trmJ mutant revealed that TrmJ catalyzes formation of Cm, Um, and, unexpectedly, Am. Defined in vitro analyses revealed that tRNAMet(CAU) and tRNATrp(CCA) are substrates for Cm formation, tRNAGln(UUG), tRNAPro(UGG), tRNAPro(CGG) and tRNAHis(GUG) for Um, and tRNAPro(GGG) for Am. tRNASer(UGA), previously observed as a TrmJ substrate in Escherichia coli, was not modified by PA14 TrmJ. Position 32 was confirmed as the TrmJ target for Am in tRNAPro(GGG) and Um in tRNAGln(UUG) by mass spectrometric analysis. Crystal structures of the free catalytic N-terminal domain of TrmJ show a 2-fold symmetrical dimer with an active site located at the interface between the monomers and a flexible basic loop positioned to bind tRNA, with conformational changes upon binding of the SAM analog sinefungin. The loss of TrmJ rendered PA14 sensitive to H2O2 exposure, with reduced expression of oxyR-recG, katB-ankB, and katE These results reveal that TrmJ is a tRNA:Cm32/Um32/Am32 methyltransferase involved in translational fidelity and the oxidative stress response. PMID- 27683220 TI - AKAP12 mediates PKA-induced phosphorylation of ATR to enhance nucleotide excision repair. AB - Loss-of-function in melanocortin 1 receptor (MC1R), a GS protein-coupled receptor that regulates signal transduction through cAMP and protein kinase A (PKA) in melanocytes, is a major inherited melanoma risk factor. Herein, we report a novel cAMP-mediated response for sensing and responding to UV-induced DNA damage regulated by A-kinase-anchoring protein 12 (AKAP12). AKAP12 is identified as a necessary participant in PKA-mediated phosphorylation of ataxia telangiectasia mutated and Rad3-related (ATR) at S435, a post-translational event required for cAMP-enhanced nucleotide excision repair (NER). Moreover, UV exposure promotes ATR-directed phosphorylation of AKAP12 at S732, which promotes nuclear translocation of AKAP12-ATR-pS435. This complex subsequently recruits XPA to UV DNA damage and enhances 5' strand incision. Preventing AKAP12's interaction with PKA or with ATR abrogates ATR-pS435 accumulation, delays recruitment of XPA to UV damaged DNA, impairs NER and increases UV-induced mutagenesis. Our results define a critical role for AKAP12 as an UV-inducible scaffold for PKA-mediated ATR phosphorylation, and identify a repair complex consisting of AKAP12-ATR-pS435-XPA at photodamage, which is essential for cAMP-enhanced NER. PMID- 27683224 TI - Antisense oligonucleotides delivered to the amniotic cavity in utero modulate gene expression in the postnatal mouse. AB - Congenital diseases account for a large portion of pediatric illness. Prenatal screening and diagnosis permit early detection of many genetic diseases. Fetal therapeutic strategies to manage disease processes in utero represent a powerful new approach for clinical care. A safe and effective fetal pharmacotherapy designed to modulate gene expression ideally would avoid direct mechanical engagement of the fetus and present an external reservoir of drug. The amniotic cavity surrounding the fetus could serve as an ideal drug reservoir. Antisense oligonucleotides (ASOs) are an established tool for the therapeutic modulation of gene expression. We hypothesize that ASOs administered to the amniotic cavity will gain entry to the fetus and modulate gene expression. Here, we show that an ASO targeting MALAT1 RNA, delivered by transuterine microinjection into the mouse amniotic cavity at embryonic day 13-13.5, reduces target RNA expression for up to 4 weeks after birth. A similarly delivered ASO targeting a causal splice site mutation for Usher syndrome corrects gene expression in the inner ear, a therapeutically relevant target tissue. We conclude that intra-amniotic delivery of ASOs is well tolerated and produces a sustained effect on postnatal gene expression. Transuterine delivery of ASOs is an innovative platform for developing fetal therapeutics to efficaciously treat congenital disease. PMID- 27683225 TI - Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis. AB - By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (>=18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis. PMID- 27683226 TI - Mechanical thrombectomy in patients with tumour-related ischaemic stroke. AB - Ischaemic stroke is a common cause of death and incapacity and is related in most cases to vascular disease. Intracranial vessel occlusion due to tumour emboli is a rare entity and adequate treatment for this condition is not defined. The use of mechanical thrombectomy devices is considered the treatment of choice for major intracranial vessel occlusion; however, no recommendation can be made in the case of tumour thrombembolia. This report describes two cases who presented with a middle cerebral artery occlusion due to tumour emboli and that were treated using the Solitaire thrombectomy device. PMID- 27683223 TI - Chtop (Chromatin target of Prmt1) auto-regulates its expression level via intron retention and nonsense-mediated decay of its own mRNA. AB - Chtop (chromatin target of Prmt1) regulates various aspects of gene expression including transcription and mRNA export. Despite these important functions, the regulatory mechanism underlying Chtop expression remains undetermined. Using Chtop-expressing human cell lines, we demonstrate that Chtop expression is controlled via an autoregulatory negative feedback loop whereby Chtop binds its own mRNA to retain intron 2 during splicing; a premature termination codon present at the 5' end of intron 2 leads to nonsense-mediated decay of the mRNA. We also show that Chtop interacts with exon 2 of Chtop mRNA via its arginine glycine-rich (RG) domain, and with intron 2 via its N-terminal (N1) domain; both are required for retention of intron 2. In addition, we show that hnRNP H accelerates intron 2 splicing of Chtop mRNA in a manner dependent on Chtop expression level, suggesting that Chtop and hnRNP H regulate intron 2 retention of Chtop mRNA antagonistically. Thus, the present study provides a novel molecular mechanism by which mRNA and protein levels are constitutively regulated by intron retention. PMID- 27683227 TI - Psychopathic personality traits in 5 year old twins: the importance of genetic and shared environmental influences. AB - There is limited research on the genetic and environmental bases of psychopathic personality traits in children. In this study, psychopathic personality traits were assessed in a total of 1189 5-year-old boys and girls drawn from the Preschool Twin Study in Sweden. Psychopathic personality traits were assessed with the Child Problematic Traits Inventory, a teacher-report measure of psychopathic personality traits in children ranging from 3 to 12 years old. Univariate results showed that genetic influences accounted for 57, 25, and 74 % of the variance in the grandiose-deceitful, callous-unemotional, and impulsive need for stimulation dimensions, while the shared environment accounted for 17, 48 and 9 % (n.s.) in grandiose-deceitful and callous-unemotional, impulsive-need for stimulation dimensions, respectively. No sex differences were found in the genetic and environmental variance components. The non-shared environment accounted for the remaining 26, 27 and 17 % of the variance, respectively. The three dimensions of psychopathic personality were moderately correlated (0.54 0.66) and these correlations were primarily mediated by genetic and shared environmental factors. In contrast to research conducted with adolescent and adult twins, we found that both genetic and shared environmental factors influenced psychopathic personality traits in early childhood. These findings indicate that etiological models of psychopathic personality traits would benefit by taking developmental stages and processes into consideration. PMID- 27683229 TI - Rapamycin suppresses hypoxia/reoxygenation-induced islet injury by up-regulation of miR-21 via PI3K/Akt signalling pathway. AB - OBJECTIVES: Increasing evidences indicate that microRNAs may play a critical role in the regulation of hypoxia/reoxygenation (H/R) injury, and their expression is associated with mTORC activity. We propose that rapamycin modulates H/R-induced islets injury by regulating microRNA expression. MATERIALS AND METHODS: We investigated whether rapamycin treatment could alter the expression profile of miRNAs in islets. Furthermore, we assessed the islet apoptosis and function after H/R or syngeneic islet transplantation. RESULTS: We found that rapamycin treatment significantly decreased H/R-induced islet apoptosis, and improved islet function in vivo and in vitro, and that miR-21 gene transcription is controlled by rapamycin. When the PI3k/Akt signalling pathways was blocked by wortmannin, the up-regulative effects of rapamycin on miR-21 expression were inhibited in vitro. Furthermore, our study clearly demonstrates that miR-21 is essential for the rapamycin-mediated protection islets against H/R injury. DISCUSSION: Our findings indicate that up-regulation of miR-21 function in islets by treatment with rapamycin or overexpression of the miR-21 could represent a potential new therapy for the treatment of H/R injury. CONCLUSION: The results of this study clearly suggest that rapamycin exerts its inhibitory effects on islets H/R injury by inducing miR-21 expression via PI3K/Akt. PMID- 27683228 TI - Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats. AB - Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1beta was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1beta. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons. PMID- 27683230 TI - Effects of Gadodiamide on cell proliferation and collagen production in cultured human dermal fibroblasts. AB - Nephrogenic systemic fibrosis (NSF) is a disease characterized by fibrosis of the systemic organs in patients with renal failure. Following the findings of recent epidemiological studies and the finding of gadolinium (Gd) in the skin tissue of NSF patients, it is now definitely known that the use of Gd contrast agents can trigger NSF. To date, however, the exact mechanism underlying the induction of fibrosis in various organs by Gd remains unexplained. This study was undertaken to evaluate the influence of Gd on the proliferation activity and collagen production of cultured fibroblasts. Normal human dermis-derived fibroblasts were incubated in the presence of gadodiamide (GA) in the concentration range of 5 * 10-7 to 5 * 10-3 M. The proliferation activity of the cells was assessed on the basis of the cell counts in the fibroblast growth curve and the DNA-synthetic activity of the cells (indicator; level of 3H-thymidine uptake by cells). The collagen production was evaluated by densitometric measurement of the quantity of collagen through electrophoresis and fluorography after incorporation of 3H proline into the procollagens. Furthermore, the expression levels of the genes for type I and III collagen were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. The cell count tended to be higher when the fibroblasts were incubated in medium containing GA in the concentration range of 5 * 10-7 to 5 * 10-4M as compared to that in the GA-free control cultures; furthermore, the DNA-synthetic activity also rose in a concentration-dependent manner in the GA-treated group as compared to that in the control group. No significant changes in either the collagen production or the collagen gene expression levels were noted in cultures containing GA at concentrations between 5 * 10-7 and 5 * 10-3 M. These results suggest that the formation of sclerosing lesions in patients with NSF may be attributable to the effect of GA of enhancing the growth activity of fibroblasts. PMID- 27683231 TI - Nano-Bio Engineered Carbon Dot-Peptide Functionalized Water Dispersible Hyperbranched Polyurethane for Bone Tissue Regeneration. AB - The present study delves into a combined bio-nano-macromolecular approach for bone tissue engineering. This approach relies on the properties of an ideal scaffold material imbued with all the chemical premises required for fostering cellular growth and differentiation. A tannic acid based water dispersible hyperbranched polyurethane is fabricated with bio-nanohybrids of carbon dot and four different peptides (viz. SVVYGLR, PRGDSGYRGDS, IPP, and CGGKVGKACCVPTKLSPISVLYK) to impart target specific in vivo bone healing ability. This polymeric bio-nanocomposite is blended with 10 wt% of gelatin and examined as a non-invasive delivery vehicle. In vitro assessment of the developed polymeric system reveals good osteoblast adhesion, proliferation, and differentiation. Aided by this panel of peptides, the polymeric bio-nanocomposite exhibits in vivo ectopic bone formation ability. The study on in vivo mineralization and vascularization reveals the occurrence of calcification and blood vessel formation. Thus, the study demonstrates carbon dot/peptide functionalized hyperbranched polyurethane gel for bone tissue engineering application. PMID- 27683232 TI - Detection of Kayser-Fleischer ring using Scheimpflug imaging. PMID- 27683233 TI - Should nurses be role models for healthy lifestyles? Results from a modified Delphi study. AB - AIM: To explore the expectation that nurses should be role models for healthy behaviours. BACKGROUND: Nurses are expected to be role models for healthy behaviours. Whether this is a realistic and acceptable expectation has not been explored. DESIGN: Modified Policy Delphi study with two rounds of data collection. METHOD: Purposive sampling was used to explore areas of agreement and disagreement among six stakeholder groups who influence nursing roles: practising nurses, nursing students, service users, policy makers, workforce development leads and stakeholders working in nurse education. Two rounds of a modified Policy Delphi study were conducted between February - June 2015. The first round used telephone interviews for an open exploration of opinions. The second round used attitude statements to explore convergence and divergence of opinions across stakeholder groups. Responses were analysed thematically. RESULTS: Policy and professional discourse that asserts that nurses should be healthy role models was seen as unrealistic and unhelpful. Contrary to the view that nurses should epitomize and demonstrate healthy behaviours to encourage patients and to be credible in advice, stakeholders agreed that it was more important to be seen as 'human' and understand the challenges of health behaviour change. Student and practising nurses did not see role modelling healthy behaviours as a reasonable professional expectation. CONCLUSIONS: The findings challenge the assumptions underpinning the argument that nurses be healthy role models. Further research is needed to understand the views of frontline nurses and to further explore avenues by which health services staff health can be improved. PMID- 27683234 TI - In memoriam: Donald H. Gilden, M.D. PMID- 27683237 TI - Mutation analysis of FGFR1-3 in 11 Japanese patients with syndromic craniosynostoses. AB - Syndromic craniosynostoses usually occur as single gene disorders. In this study, we analyzed FGFR1-3 genes in four patients with Crouzon syndrome (CS), four patients with Pfeiffer syndrome type 2 (PS-2), one patient with Jackson-Weiss syndrome (JWS), and two patients (sisters) with Muenke syndrome (MS). FGFR2 and FGFR3 mutations were identified in 10 of the 11 patients. Notably, we found a novel FGFR2 p.Asn549Thr mutation in a patient with CS, and a novel FGFR2 p.Ser347Cys mutation in a patient with JWS (thus, this patient was turned out to have an FGFR2-related PS-variant). We also identified an FGFR2 p.Ser252Leu mutation in a phenotypically normal father of a daughter with CS, and an FGFR3 p.Pro250Arg mutation in a mildly macrocephalic father of sisters with MS. These findings, together with previous data, imply that the same FGFR2 mutations can be associated with a wide range of phenotypes including clinically different forms of syndromic craniosynostosis and apparently normal phenotype, depending on other (epi)genetic and environmental factors. Thus, genetic studies are recommended not only for obviously affected individuals but also for family members with apparently normal phenotype or non-specific subtle abnormal phenotype, to allow for pertinent genetic counseling. (c) 2016 Wiley Periodicals, Inc. PMID- 27683238 TI - Sleep disturbances in irritable bowel syndrome: a systematic review. AB - BACKGROUND: Sleep disturbances are well-documented among persons with irritable bowel syndrome (IBS). Difficulty in falling asleep, shorter sleep time, frequent arousal and awakenings, or non-restorative sleep are the most common manifestations. Sleep disturbances are also related to a higher risk of having IBS. Some researchers have provided evidence of a positive association between poorer subjective sleep quality and increased severity and frequency in gastrointestinal (GI) symptoms in those with IBS. However, findings from studies using objective sleep and activity measures, such as polysomnography and actigraphy, are inconclusive. PURPOSE: This systematic review of the literature between 1990 and 2015 evaluates the evidence of sleep disturbances in adults with IBS and their relationship with GI symptoms. PMID- 27683235 TI - Induction of varicella zoster virus DNA replication in dissociated human trigeminal ganglia. AB - Varicella zoster virus (VZV), a human neurotropic alphaherpesvirus, becomes latent after primary infection and reactivates to produce zoster. To study VZV latency and reactivation, human trigeminal ganglia removed within 24 h after death were mechanically dissociated, randomly distributed into six-well tissue culture plates and incubated with reagents to inactivate nerve growth factor (NGF) or phosphoinositide 3-kinase (PI3-kinase) pathways. At 5 days, VZV DNA increased in control and PI3-kinase inhibitor-treated cultures to the same extent, but was significantly more abundant in anti-NGF-treated cultures (p = 0.001). Overall, VZV DNA replication is regulated in part by an NGF pathway that is PI3-kinase-independent. PMID- 27683239 TI - Gene duplications circumvent trade-offs in enzyme function: Insect adaptation to toxic host plants. AB - Herbivorous insects and their adaptations against plant toxins provide striking opportunities to investigate the genetic basis of traits involved in coevolutionary interactions. Target site insensitivity to cardenolides has evolved convergently across six orders of insects, involving identical substitutions in the Na,K-ATPase gene and repeated convergent gene duplications. The large milkweed bug, Oncopeltus fasciatus, has three copies of the Na,K-ATPase alpha-subunit gene that bear differing numbers of amino acid substitutions in the binding pocket for cardenolides. To analyze the effect of these substitutions on cardenolide resistance and to infer possible trade-offs in gene function, we expressed the cardenolide-sensitive Na,K-ATPase of Drosophila melanogaster in vitro and introduced four distinct combinations of substitutions observed in the three gene copies of O. fasciatus. With an increasing number of substitutions, the sensitivity of the Na,K-ATPase to a standard cardenolide decreased in a stepwise manner. At the same time, the enzyme's overall activity decreased significantly with increasing cardenolide resistance and only the least substituted mimic of the Na,K-ATPase alpha1C copy maintained activity similar to the wild-type enzyme. Our results suggest that the Na,K-ATPase copies in O. fasciatus have diverged in function, enabling specific adaptations to dietary cardenolides while maintaining the functionality of this critical ion carrier. PMID- 27683240 TI - Protein Crystallization in an Actuated Microfluidic Nanowell Device. AB - Protein crystallization is a major bottleneck of structure determination by X-ray crystallography, hampering the process by years in some cases. Numerous matrix screening trials using significant amounts of protein are often applied, while a systematic approach with phase diagram determination is prohibited for many proteins that can only be expressed in small amounts. Here, we demonstrate a microfluidic nanowell device implementing protein crystallization and phase diagram screening using nanoscale volumes of protein solution per trial. The device is made with cost-effective materials and is completely automated for efficient and economical experimentation. In the developed device, 170 trials can be realized with unique concentrations of protein and precipitant established by gradient generation and isolated by elastomeric valving for crystallization incubation. Moreover, this device can be further downscaled to smaller nanowell volumes and larger scale integration. The device was calibrated using a fluorescent dye and compared to a numerical model where concentrations of each trial can be quantified to establish crystallization phase diagrams. Using this device, we successfully crystallized lysozyme and C-phycocyanin, as visualized by compatible crystal imaging techniques such as bright-field microscopy, UV fluorescence, and second-order nonlinear imaging of chiral crystals. Concentrations yielding observed crystal formation were quantified and used to determine regions of the crystallization phase space for both proteins. Low sample consumption and compatibility with a variety of proteins and imaging techniques make this device a powerful tool for systematic crystallization studies. PMID- 27683241 TI - Sex dependent alterations in mitochondrial electron transport chain proteins following neonatal rat cerebral hypoxic-ischemia. AB - Males are more susceptible to brain mitochondrial bioenergetic dysfunction following neonatal cerebral hypoxic-ischemia (HI) than females. Mitochondrial biogenesis has been implicated in the cellular response to HI injury, but sex differences in biogenesis following HI have not been described. We tested the hypothesis that mitochondrial biogenesis or the expression of mitochondrial electron transport chain (ETC) proteins are differentially stimulated in the brains of 8 day old male and female rats one day following HI, and promoted by treatment with acetyl-L-carnitine (ALCAR). There were no sex differences in mitochondrial mass, as reflected by the ratio of mitochondrial to nuclear DNA (mtDNA/nDNA) and citrate synthase enzyme activity present one day following HI or sham surgery. There was an increase in mtDNA/nDNA, however, in the hypoxic and ischemic (ipsilateral) hemisphere after HI in both male and female brains at one day post-injury, which was suppressed by ALCAR. Citrate synthase activity was increased in the ipsilateral hemisphere of ALCAR treated male and female brain. Most importantly, the levels of representative mitochondrial proteins present in ETC complexes I, II and IV increased substantially one day following HI in female, but not male brain. This sex difference is consistent with the increase in the mitochondrial biogenesis-associated transcription factor NRF-2/GABPalpha following HI in females, in contrast to the decrease observed with males. In conclusion, the female sex-selective increase in ETC proteins following HI may at least partially explain the relative female resilience to mitochondrial respiratory impairment and neuronal death that occur after HI. PMID- 27683243 TI - The Role of Policy and Institutions on Health Spending. AB - This paper investigates the impact of policies and institutions on health expenditures for a large panel of Organisation for Economic Co-operation and Development countries for the period of 2000-2010. A set of 20 policy and institutional indicators developed by the Organisation for Economic Co-operation and Development are integrated into a theoretically motivated econometric framework, alongside control variables related to demographic (dependency ratio) and non-demographic (income, prices and technology) drivers of health expenditures per capita. Although a large share of cross-country differences in public health expenditures can be explained by demographic and economic factors (around 71%), cross-country variations in policies and institutions also have a significant influence, explaining most of the remaining difference in public health spending (23%). Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27683242 TI - Kinetic and mutational studies of the adenosine diphosphate ribose hydrolase from Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis represents one of the world's most devastating infectious agents - with one third of the world's population infected and 1.5 million people dying each year from this deadly pathogen. As part of an effort to identify targets for therapeutic intervention, we carried out the kinetic characterization of the product of gene rv1700 of M. tuberculosis. Based on its sequence and its structure, the protein had been tentatively identified as a pyrophosphohydrolase specific for adenosine diphosphate ribose (ADPR), a compound involved in various pathways including oxidative stress response and tellurite resistance. In this work we carry out a kinetic, mutational and structural investigation of the enzyme, which provides a full characterization of this Mt ADPRase. Optimal catalytic rates were achieved at alkaline pH (7.5-8.5) with either 0.5-1 mM Mg2+ or 0.02-1 mM Mn2+. K m and k cat values for hydrolysis of ADPR with Mg2+ ions are 200 +/- 19 MUM and 14.4 +/- 0.4 s-1, and with Mn2+ ions are 554 +/- 64 MUM and 28.9 +/- 1.4 s-1. Four residues proposed to be important in the catalytic mechanism of the enzyme were individually mutated and the kinetics of the mutant enzymes were characterized. In the four cases, the K m increased only slightly (2- to 3-fold) but the k cat decreased significantly (300 to 1900-fold), confirming the participation of these residues in catalysis. An analysis of the sequence and structure conservation patterns in Nudix ADPRases permits an unambiguous identification of members of the family and provides insight into residues involved in catalysis and their participation in substrate recognition in the Mt-ADPRase. PMID- 27683246 TI - Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta analysis. AB - OBJECTIVE: To examine the effect of transcatheter aortic valve implantation (TAVI) versus surgical replacement of an aortic valve (SAVR) in patients with severe aortic stenosis at low and intermediate risk of perioperative death. DESIGN: Systematic review and meta-analysis DATA SOURCES: Medline, Embase, and Cochrane CENTRAL. STUDY SELECTION: Randomized trials of TAVI compared with SAVR in patients with a mean perioperative risk of death <8%. REVIEW METHODS: Two reviewers independently extracted data and assessed risk of bias for outcomes important to patients that were selected a priori by a parallel guideline committee, including patient advisors. We used the GRADE system was used to quantify absolute effects and quality of evidence. RESULTS: 4 trials with 3179 patients and a median follow-up of two years were included. Compared with SAVR, transfemoral TAVI was associated with reduced mortality (risk difference per 1000 patients: -30, 95% confidence interval -49 to -8, moderate certainty), stroke ( 20, -37 to 1, moderate certainty), life threatening bleeding (-252, -293 to -190, high certainty), atrial fibrillation (-178, -150 to -203, moderate certainty), and acute kidney injury (-53, -39 to -62, high certainty) but increased short term aortic valve reintervention (7, 1 to 21, moderate certainty), permanent pacemaker insertion (134, 16 to 382, moderate certainty), and moderate or severe symptoms of heart failure (18, 5 to 34, moderate certainty). Compared with SAVR, transapical TAVI was associated higher mortality (57, -16 to 153, moderate certainty, P=0.015 for interaction between transfemoral versus transapical TAVI) and stroke (45, -2 to 125, moderate certainty, interaction P=0.012). No study reported long term follow-up, which is particularly important for structural valve deterioration. CONCLUSIONS: Many patients, particularly those who have a shorter life expectancy or place a lower value on the risk of long term valve degeneration, are likely to perceive net benefit with transfemoral TAVI versus SAVR. SAVR, however, performs better than transapical TAVI, which is of interest to patients who are not candidates for transfemoral TAVI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016042879. PMID- 27683245 TI - Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans. AB - Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro oxidants, antioxidants can both lengthen and shorten lifespan, dependent on concentration, genotypes, and conditions. The effects of antioxidants thus reveal an inverted U-shaped dose-response relationship between ROS levels and lifespan. In addition, we observed that RSV can act additively to both NAC and paraquat, to dramatically increase lifespan. This suggests that the effect of compounds that modulate ROS levels can be additive when their loci of action or mechanisms of action are sufficiently distinct. PMID- 27683247 TI - Mobility, balance and frailty in community-dwelling older adults: What is the best 1-year predictor of falls? AB - AIM: The present study aimed, first, to compare the ability to predict falls over 12 months for three measures - mobility, balance and frailty. Second, among the three domains of frailty - physical, psychological and social - we investigated what is the strongest predictor of falls. METHODS: A total of 192 community dwelling older adults (age 73.0 +/- 6.2 years; 62% women) were involved in this longitudinal study. The Timed Up and Go (TUG) test, One Leg Standing (OLS) test and the Tilburg Frailty Indicator (TFI) were respectively used to measure mobility, balance and frailty. The TFI is a questionnaire based on a multidimensional conceptualization of frailty consisting of 15 items in three domains (physical, psychological and social). Falls were self-reported during the 12-month follow up. Logistic regression models, adjusted for interesting variables, were carried out to predict the risk of falls. RESULTS: History of falls and chronic conditions were the indicators more strongly related with falls over 12 months. The TFI resulted as a stronger predictor of falls when compared with the TUG and OLS tests. The explained variance of the three models was 31.2%, 22.4% and 22.2%, respectively. The TFI was significantly associated with falls (P < 0.001), whereas the TUG and the OLS were not (P > 0.05). Among the three frailty domains, physical (P < 0.001) and psychological (P = 0.041) domains were significant predictors of falls. CONCLUSIONS: The findings showed that the TFI might be an effective tool for predicting falls at 12 months in aged populations, probably because it is able to capture the multifactorial facets that can lead to falls. Geriatr Gerontol Int 2017; 17: 1463-1469. PMID- 27683248 TI - The Arrival of Homo sapiens into the Southern Cone at 14,000 Years Ago. AB - The Arroyo Seco 2 site contains a rich archaeological record, exceptional for South America, to explain the expansion of Homo sapiens into the Americas and their interaction with extinct Pleistocene mammals. The following paper provides a detailed overview of material remains found in the earliest cultural episodes at this multi-component site, dated between ca. 12,170 14C yrs B.P. (ca. 14,064 cal yrs B.P.) and 11,180 14C yrs B.P. (ca. 13,068 cal yrs B.P.). Evidence of early occupations includes the presence of lithic tools, a concentration of Pleistocene species remains, human-induced fractured animal bones, and a selection of skeletal parts of extinct fauna. The occurrence of hunter-gatherers in the Southern Cone at ca. 14,000 cal yrs B.P. is added to the growing list of American sites that indicate a human occupation earlier than the Clovis dispersal episode, but posterior to the onset of the deglaciation of the Last Glacial Maximum (LGM) in the North America. PMID- 27683249 TI - AhpA is a peroxidase expressed during biofilm formation in Bacillus subtilis. AB - Organisms growing aerobically generate reactive oxygen species such as hydrogen peroxide. These reactive oxygen molecules damage enzymes and DNA, potentially causing cell death. In response, Bacillus subtilis produces at least nine potential peroxide-scavenging enzymes; two belong to the alkylhydroperoxide reductase (Ahp) class of peroxidases. Here, we explore the role of one of these Ahp homologs, AhpA. While previous studies demonstrated that AhpA can scavenge peroxides and thus defend cells against peroxides, they did not clarify when during growth the cell produces AhpA. The results presented here show that the expression of ahpA is regulated in a manner distinct from that of the other peroxide-scavenging enzymes in B. subtilis. While the primary Ahp, AhpC, is expressed during exponential growth and stationary phase, these studies demonstrate that the expression of ahpA is dependent on the transition-state regulator AbrB and the sporulation and biofilm formation transcription factor Spo0A. Furthermore, these results show that ahpA is specifically expressed during biofilm formation, and not during sporulation or stationary phase, suggesting that derepression of ahpA by AbrB requires a signal other than those present upon entry into stationary phase. Despite this expression pattern, ahpA mutant strains still form and maintain robust biofilms, even in the presence of peroxides. Thus, the role of AhpA with regard to protecting cells within biofilms from environmental stresses is still uncertain. These studies highlight the need to further study the Ahp homologs to better understand how they differ from one another and the unique roles they may play in oxidative stress resistance. PMID- 27683251 TI - Intraprostatic Reflux of Urine Induces Inflammation in a Rat. AB - BACKGROUND: We examined whether urine reflux into the prostate can induce prostatic inflammation in a rat and evaluated the effect of alpha1-adrenoreceptor antagonist. METHODS: Experiment 1: Male Sprague-Dawley rats were injected with 500 ul of Evans Blue through the urethral orifice. Intravesical pressure was measured, and the prostate was excised to evaluate urine reflux. Experiment 2: Rats were injected with 500 ul urine or saline (control) from the urethral orifice. Silodosin (200 ug/kg/day) was administered to the silodosin group. We evaluated histopathology, the expression of proinflammatory cytokines and oxidative stress markers of the prostate on day 7, after assessing the prostatic microcirculation and cystometrogram. RESULTS: Experiment 1: The histopathology showed that Evans Blue instilled through the urethral orifice entered the prostatic ducts. Intravesical pressure during Evans Blue instillation was 47.7 +/ 1.6 cmH2 O (mean +/- standard error). Experiment 2: On day 7 after urine instillation through the urethral orifice, histopathology showed infiltrated inflammatory cells in the peri-glandular stroma. Inflammation-associated proteins (IL-1alpha, IL-1beta, IL-6, and TNFalpha) were upregulated in the urine-instilled rats but not in the silodosin group. Erythrocyte speed on the prostatic surface, immunostaining for hypoxyprobe, and quantification of oxidative stress markers (MDA and HIF-1alpha) demonstrated prostatic hypoxia in the urine-instilled rats, which was ameliorated in the silodosin group. Cystometrogram revealed a shorter intercontraction interval in the urine-instilled rats, which was prolonged in the silodosin group. CONCLUSIONS: Urine reflux into the prostatic duct induces abacterial prostatitis. Silodosin relieved prostatic inflammation and bladder overactivity by increasing microcirculation in the prostate. Prostate 77:164-172, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27683252 TI - Visual Interpretation of Biomedical Time Series Using Parzen Window-Based Density Amplitude Domain Transformation. AB - This study proposes a new method suitable for the visual analysis of biomedical time series that is based on the examination of biomedical signals in the density amplitude domain. Toward this goal, we employed two publicly available datasets. In the first stage of the study, density coefficients were computed separately by using the Parzen Windowing method for each class of raw attribute data. Then, differences between classes were determined visually by using density coefficients and their related amplitudes. Visual interpretation of the processed data gave more successful classification results compared with the raw data in the first stage. Next the density-amplitude representations of the raw data were classified using classifiers (SVM, KNN and Naive Bayes). The raw data (time amplitude) and their frequency-amplitude representation were also classified using the same classification methods. The statistical results showed that the proposed method based on the density-amplitude representation increases the classification success up to 55% compared with methods using the time-amplitude domain and up to 75% compared with methods based on the frequency-amplitude domain. Finally, we have highlighted several statistical analysis suggestions as a result of the density-amplitude representation. PMID- 27683250 TI - Human metapneumovirus Induces Reorganization of the Actin Cytoskeleton for Direct Cell-to-Cell Spread. AB - Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. In contrast, inhibition of actin polymerization or alterations to Rho GTPase signaling pathways significantly decreased cell-to-cell spread. Furthermore, viral proteins and viral RNA were detected in intercellular extensions, suggesting direct transfer of viral genetic material to new target cells. While roles for paramyxovirus matrix and fusion proteins in membrane deformation have been previously demonstrated, we show that the HMPV phosphoprotein extensively co-localized with actin and induced formation of cellular extensions when transiently expressed, supporting a new model in which a paramyxovirus phosphoprotein is a key player in assembly and spread. Our results reveal a novel mechanism for HMPV direct cell-to cell spread and provide insights into dissemination of respiratory viruses. PMID- 27683255 TI - An Approach for Zika Virus Inhibition Using Homology Structure of the Envelope Protein. AB - To find an effective drug for Zika virus, it is important to understand how numerous proteins which are critical for the virus' structure and function interact with their counterparts. One approach to inhibiting the flavivirus is to deter its ability to bind onto glycoproteins; however, the crystal structures of envelope proteins of the ever-evolving viral strains that decipher glycosidic or drug-molecular interactions are not always available. To fill this gap, we are reporting a holistic, simulation-based approach to predict compounds that will inhibit ligand binding onto a structurally unresolved protein, in this case the Zika virus envelope protein (ZVEP), by developing a three-dimensional general structure and analyzing sites at which ligands and small drug-like molecules interact. By examining how glycan molecules and small-molecule probes interact with a freshly resolved ZVEP homology model, we report the susceptibility of ZVEP to inhibition via two small molecules, ZINC33683341 and ZINC49605556-by preferentially binding onto the primary receptor responsible for the virus' virulence. Antiviral activity was confirmed when ZINC33683341 was tested in cell culture. We anticipate the results to be a starting point for drug discovery targeting Zika virus and other emerging pathogens. PMID- 27683253 TI - Relationship of specific MRI findings to treatment outcomes in patients receiving transforaminal epidural steroid injections. AB - OBJECTIVES: To determine whether specific MRI findings are related to outcomes after lumbar transforaminal epidural steroid injections (TFESI) and to assess the inter-rater reliability of imaging diagnosis. MATERIALS AND METHODS: A prospective outcomes study on 156 consecutive patients with 1-month follow-up outcomes data and MRI within 3 months of TFESI was conducted. Pain levels (numerical rating scale) (NRS) were recorded prior to injection. Overall 'improvement' was determined using the Patients Global Impression of Change (PGIC) scale and NRS data were collected at three time points post injection. Two radiologists independently evaluated all images blinded to treatment outcome for reliability of diagnosis. The Chi-square test compared MRI findings for the senior radiologist to 'improvement'. NRS change scores were compared to MRI findings with the unpaired t-test or ANOVA. Kappa and percent agreement assessed inter-rater agreement of diagnosis. RESULTS: The only abnormality linked to 'improvement' (p = 0.03) and higher NRS change scores (p = 0.0001) at 1 month was the disc herniation morphology 'protrusion + sequestration'. Patients with degeneration by osteophytes (p = 0.034), grade 3 foraminal nerve root compression (p = 0.01) and foraminal/extraforaminal location of herniation (p = 0.014) also had higher 1 month NRS change scores. Reliability of diagnosis was 'fair' to 'substantial' depending on MRI findings. CONCLUSIONS: Patients with disc protrusion plus sequestration were significantly more likely to report overall improvement and more pain reduction at 1 month. Higher pain reduction was noted in patients with degeneration by osteophytes, grade 3 foraminal nerve root compression, or foraminal/extraforaminal disc herniation location. PMID- 27683254 TI - RARS2 Mutations: Is Pontocerebellar Hypoplasia Type 6 a Mitochondrial Encephalopathy? AB - Mutations in the mitochondrial arginyl tRNA synthetase (RARS2) gene are associated with Pontocerebellar Hypoplasia type 6 (PCH6). Here we report two patients, compound heterozygous for RARS2 mutations, presenting with early onset epileptic encephalopathy and (progressive) atrophy of both supra- and infratentorial structures. Early pontocerebellar hypoplasia was virtually absent and respiratory chain (RC) defects could not be detected in muscle biopsies. Both patients carried a novel missense mutation c.1544A>G (p.(Asp515Gly)) in combination with either a splice site (c.297+2T>G) or a frameshift (c.452_454insC) mutation. The splice site mutation induced skipping of exon 4.These two patients expand the phenotypical spectrum associated with RARS2 mutations beyond the first report of PCH6 by Edvardson and colleagues. We propose to classify RARS2-associated phenotypes as an early onset mitochondrial encephalopathy, since this is more in agreement with both clinical presentation and underlying genetic cause. PMID- 27683256 TI - Minipig-BMSCs Combined with a Self-Setting Calcium Phosphate Paste for Bone Tissue Engineering. AB - Calcium phosphate cements (CPCs) are a new generation of bone repair materials with good biocompatibility for various stem cells. The minipig is a recommended large animal model for bone engineering research. This study aimed to evaluate the feasibility of utilizing CPC scaffolds for the adhesion, proliferation, and osteogenic differentiation of minipig's bone marrow mesenchymal stem cells (pBMSCs). Passage 3 pBMSCs were seeded on the CPC scaffold and cultured with osteogenic culture medium (osteogenic group) or normal medium (control group). The density of viable cells increased in both groups, and pBMSCs firmly attached and spread well on the CPC scaffold. The alkaline phosphatase (ALP) activity in the osteogenic group had significantly increased on day 7 (D7) and peaked on D14. qRT-PCR revealed that mRNA levels of ALP and three osteogenic marker genes were significantly higher on D4, D7, and D14 in the osteogenic group. Alizarin Red S staining showed a significantly higher degree of bone mineralization from D7, D14 to D21 in the osteogenic group. These results indicated that pBMSCs can attach, proliferate well on CPC scaffold, and be successfully induced to differentiate into osteogenic cells. Our findings may be helpful for bone tissue engineering and the studies of bone regeneration. PMID- 27683257 TI - Global Budget Payment: Proposing the CAP Framework. AB - To control ever-increasing costs, global budget payment has gained attention but has unclear impacts on health care systems. We propose the CAP framework that helps navigate 3 domains of difficult design choices in global budget payment: Constraints in resources (capitation vs facility-based budgeting; hard vs soft budget constraints), Agent-principal in resource allocation (individual vs group providers in resource allocation; single vs multiple pipes), and Price adjustment. We illustrate the framework with empirical examples and draw implications for policy makers. PMID- 27683258 TI - In vitro and in silico characterization of angiogenic inhibitors from Sophora interrupta. AB - Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 MUg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 MUg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 MUg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract. The antioxidative activity of SEA extract at IC50 (200 +/- 0.6 MUg/mL) is equal to that of ascorbic acid at IC50 (50 +/- 0.6 MUg/mL), and the anti-inflammatory activity of SEA extract at IC50 (150 +/- 0.2 MUg/mL) was inhibited significantly by nitric oxide (NO) production. The SEA extract significantly reduced the sprouting of new blood vessels at ID50 500 +/- 0.13 MUg/mL in the CAM assay. Gas chromatography-mass spectrometry analysis of the SEA extract detected 34 secondary metabolites, of which 6a,12a-dihydro-6H (1,3)dioxolo(5,6)benzofuro(3,2-c)chromen-3-ol (maackiain) and funiculosin formed strong hydrogen bond interactions with Lys 920, Thr 916 and Cys 919 (2H), as well as Glu 917 of VEGFR2, and these interactions were similar to those of the anti angiogenic compound axitinib. Significant findings in all the assays performed indicate that SEA extract has potential anti-angiogenic compounds that may interfere with VEGF-induced cancer malignancy. PMID- 27683259 TI - Optoelectronic properties of naphtho[2, 1-b:6, 5-b']difuran derivatives for photovoltaic application: a computational study. AB - Some important optoelectronic properties of naphtho[2,1-b:6,5-b']difuran (DPNDF) and its two derivatives have been limelighted by applying the density functional theory (DFT). Due to their low cost, high stability and earth abundance, the DPNDF and its derivatives are considered as potential organic semiconductor materials for their optoelectronics applications. Highly proficient derivatives are obtained systematically by attaching -CN (cyanide) to DPNDF at various sites. Our calculations indicate that DPNDF has a wide and direct band gap with an energy gap of 3.157 eV. Whereas the band gaps of its derivatives are found to be decreased by 88 meV for derivative "a" and 300 meV for derivative "b" as a consequence of p orbitals present in C and N atoms in derivative structures. The narrowing of the energy gap and density of states for the derivatives of DPNDF in the present investigation suggest that energy gap can be engineered for desirable optoelectronic applications via derivatives designing. Furthermore, their obtained results for optical parameters such as the dielectric and conductivity functions, reflectivity, refractive index, and the extinction coefficients endorses their aptness for optoelectronic applications. Graphical Abstract Real part of dielectric function for derivative "b". PMID- 27683261 TI - Risk factors for overnight respiratory events following sedation for magnetic resonance imaging in children with sleep apnea. AB - PURPOSE: Children with sleep apnea may be at increased risk for overnight respiratory events (ORE) following anesthesia. We sought to identify ORE risk factors in sleep apnea patients sedated for magnetic resonance imaging (MRI). METHODS: One thousand four hundred seven hospitalizations for children with sleep apnea (by ICD-9 code) occurred at our institution from 5/1/2011 to 2/1/2015. One hundred twenty-seven (9 %) encounters were solely for post-MRI observation representing 96 unique patients. The first post-MRI admission for each patient underwent chart review. ORE was defined as sustained oxygen saturation <90 % with need for increased oxygen or adjustment of respiratory support after release from recovery. Characteristics of patients with and without ORE were compared by chi squared analysis or independent samples t test. Logistic regression identified associations with ORE. RESULTS: Ten out of 96 (10.4 %) patients had ORE. The average time following sedation to ORE was 10.25 h. ORE patients were hospitalized longer (median 2 vs. 1 day, p < 0.001). Overall, patients were 55 % male, 60 % Hispanic, with median age of 5 years [IQR 2-10] and median body mass index (BMI) of 17.9 [IQR 15.2-24]. On logistic regression, apnea-hypopnea index (AHI; OR 1.007 [95 % CI 1.002-1.011]), anesthesia complication (OR 1.13 [95 % CI 1.01-1.28]), and home non-invasive positive pressure ventilation (NIV; OR 6.08 [95 % CI 1.57-26.17]) were associated with ORE. CONCLUSION: Ninety percent of children with sleep apnea admitted for overnight observation following sedated MRI did not have an ORE. AHI, anesthesia complications, and NIV use may help target higher-risk patients and avoid unnecessary hospitalizations. PMID- 27683260 TI - Synchrotron Imaging Assessment of Bone Quality. AB - Bone is a complex hierarchical structure, and its principal function is to resist mechanical forces and fracture. Bone strength depends not only on the quantity of bone tissue but also on the shape and hierarchical structure. The hierarchical levels are interrelated, especially the micro-architecture, collagen and mineral components; hence, analysis of their specific roles in bone strength and stiffness is difficult. Synchrotron imaging technologies including micro-CT and small/wide angle X-ray scattering/diffraction are becoming increasingly popular for studying bone because the images can resolve deformations in the micro architecture and collagen-mineral matrix under in situ mechanical loading. Synchrotron cannot be directly applied in vivo due to the high radiation dose but will allow researchers to carry out systematic multifaceted studies of bone ex vivo. Identifying characteristics of aging and disease will underpin future efforts to generate novel devices and interventional therapies for assessing and promoting healthy aging. With our own research work as examples, this paper introduces how synchrotron imaging technology can be used with in situ testing in bone research. PMID- 27683262 TI - Hypoxic Stress Forces Irreversible Differentiation of a Majority of Mouse Trophoblast Stem Cells Despite FGF4. AB - Hypoxic, hyperosmotic, and genotoxic stress slow mouse trophoblast stem cell (mTSC) proliferation, decrease potency/stemness, and increase differentiation. Previous reports suggest a period of reversibility in stress-induced mTSC differentiation. Here we show that hypoxic stress at 0.5% O2 decreased potency factor protein by ~60%-90% and reduced growth to nil. Hypoxia caused a 35-fold increase in apoptosis at Day 3 and a 2-fold increase at Day 6 above baseline. The baseline apoptosis rate was only 0.3%. Total protein was never less than baseline during hypoxic treatment, suggesting 0.5% O2 is a robust, nonmorbid stressor. Hypoxic stress induced ~50% of trophoblast giant cell (TGC) differentiation with a simultaneous 5- to 6-fold increase in the TGC product antiluteolytic prolactin family 3, subfamily d, member 1 (PRL3D1), despite the presence of fibroblast growth factor 4 (FGF4). Hypoxia-induced TGC differentiation was also supported by potency and differentiation mRNA marker analysis. FGF4 removal at 20% O2 committed cell fate towards irreversible differentiation at 2 days, with similar TGC percentages after an additional 3 days of culture under potency conditions when FGF4 was readded or under differentiation conditions without FGF4. However, hypoxic stress required 4 days to irreversibly differentiate cells. Runted stem cell growth, forced differentiation of fewer cells, and irreversible differentiation limit total available stem cell population. Were mTSCs to respond to stress in a similar mode in vivo, miscarriage might occur as a result, which should be tested in the future. PMID- 27683263 TI - SMAD3 Activation: A Converging Point of Dysregulated TGF-Beta Superfamily Signaling and Genetic Aberrations in Granulosa Cell Tumor Development? AB - Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human. However, our understanding of the role of cell signaling in GCT development is far from complete. Increasing lines of evidence highlight the importance of TGF-beta (TGFB) superfamily signaling in the pathogenesis of GCTs. This review draws on findings using genetically modified mouse models and human patient specimens and cell lines to reveal SMAD3 activation as a potentially key converging point of dysregulated TGFB superfamily signaling and genetic aberrations in GCT development. It is anticipated that deciphering the role of TGFB superfamily signaling cascades in ovarian tumorigenesis will help develop new therapeutic approaches for GCTs by targeting core signaling elements essential for tumor initiation, growth, and progression. PMID- 27683264 TI - Apelin (APLN) and Apelin Receptor (APLNR) in Human Ovary: Expression, Signaling, and Regulation of Steroidogenesis in Primary Human Luteinized Granulosa Cells. AB - Apelin (APLN) is a recently discovered adipokine involved in the regulation of various metabolic functions. Its receptor, APLNR, is expressed in reproductive tissues, however, its role in human ovarian cells is unknown. In this study, we identified APLN and APLNR in human ovarian follicles and analyzed their expression in granulosa cells and follicular fluid obtained from obese and nonobese patients, with or without polycystic ovary syndrome (PCOS). We also investigated the effect of APLN on steroidogenesis in cultured human luteinized granulosa cells (hGCs) from nonobese patients without PCOS. Using RT-PCR and immunoblotting, we found that APLN and APLNR were expressed in hGCs and cumulus and theca cells. We confirmed these data immunohistochemically and observed that APLNR and APLN are present in human oocytes at different stages of follicular development. In patients with PCOS, we observed that follicular fluid APLN concentration and granulosa cell APLN and APLNR mRNA expression was higher than that observed in control patients. In cultured hGCs from nonobese patients without PCOS, insulin-like growth factor 1 (IGF1) increased APLNR expression, and recombinant human APLN (APLN-13 and APLN-17) increased both basal and IGF1 induced steroid secretion. These effects on steroid production were reversed when cultured in the presence of ML221, an APLNR antagonist, which was associated with an increased 3beta-hydrosteroid dehydrogenase (HSD3B) protein concentration. We showed that these effects were dependent on the activation of the AKT and MAPK3/1 pathways using pharmacological inhibitors. Our results show that APLN and APLNR are present in human ovarian cells and APLN increases IGF1-induced steroidogenesis in granulosa cells through an increase in HSD3B protein expression and activation of the MAPK3/1 and Akt pathways. Therefore, APLN and APLNR may play a role in human follicular development and the pathogenesis of PCOS. PMID- 27683266 TI - Rosiglitazone Improves Stallion Sperm Motility, ATP Content, and Mitochondrial Function. AB - Media used for equine sperm storage often contain relatively high concentrations of glucose, even though stallion spermatozoa preferentially utilize oxidative phosphorylation (OXPHOS) over glycolysis to generate ATP and support motility. Rosiglitazone is an antidiabetic compound that enhances metabolic flexibility and glucose utilization in various cell types, but its effects on sperm metabolism are unknown. This study investigated the effects of rosiglitazone on stallion sperm function in vitro, along with the possible role of AMP-activated protein kinase (AMPK) in mediating these effects. Spermatozoa were incubated with or without rosiglitazone, GW9662 (an antagonist of peroxisome proliferator activating receptor-gamma), and compound C (CC; an AMPK inhibitor). Sperm motility, viability, reactive oxygen species production, mitochondrial membrane potential (mMP), ATP content, and glucose uptake capacity were measured. Samples incubated with rosiglitazone displayed significantly higher motility, percentage of cells with normal mMP, ATP content, and glucose uptake capacity, while sperm viability was unaffected. The percentage of spermatozoa positive for mitochondrial ROS was also significantly lower in rosiglitazone-treated samples. AMPK localized to the sperm midpiece, and its phosphorylation, was increased in rosiglitazone-treated spermatozoa. CC decreased sperm AMPK phosphorylation and reduced sperm motility, and successfully inhibited the effects of rosiglitazone. Inclusion of rosiglitazone in a room temperature sperm storage medium maintained sperm motility above 60% for 6 days, attaining significantly higher motility than sperm stored in control media. The ability of rosiglitazone to substantially alleviate the time-dependent deterioration of stallion spermatozoa by diverting metabolism away from OXPHOS and toward glycolysis has novel implications for the long-term, functional preservation of these cells. PMID- 27683265 TI - Spatial Characterization of Bioenergetics and Metabolism of Primordial to Preovulatory Follicles in Whole Ex Vivo Murine Ovary. AB - Previous work characterizing ovarian bioenergetics has defined follicular metabolism by measuring metabolic by-products in culture media. However, culture conditions perturb the native state of the follicle, and these methods do not distinguish between metabolism occurring within oocytes or granulosa cells. We applied the phasor approach to fluorescence lifetime imaging microscopy (phasor FLIM) at 740-nm two-photon excitation to examine the spatial distribution of free and protein-bound nicotinamide adenine dinucleotide hydride (NADH) during primordial through preovulatory stages of follicular development in fresh ex vivo murine neonatal and gonadotropin stimulated prepubertal ovaries. We obtained subcellular resolution phasor FLIM images of primordial through primary follicles and quantified the free/bound NADH ratio (relative NADH/NAD+) separately for oocyte nucleus and oocyte cytoplasm. We found that dynamic changes in oocyte nucleus free/bound NADH paralleled the developmental maturation of primordial to primary follicles. Immunohistochemistry of NAD+-dependent deacetylase SIRTUIN 1 (SIRT1) in neonatal ovary revealed that increasing SIRT1 expression in oocyte nuclei was inversely related to decreasing free/bound NADH during the primordial to primary follicle transition. We characterized oocyte metabolism at these early stages to be NADH producing (glycolysis/Krebs). We extended the results of prior studies to show that cumulus and mural granulosa cell metabolism in secondary through preovulatory follicles is mainly NADH producing (glycolysis/Krebs cycle), while oocyte metabolism is mainly NADH consuming (oxidative phosphorylation). Taken together, our data characterize dynamic changes in free/bound NADH and SIRT1 expression during early follicular development and confirm results from previous studies defining antral and preovulatory follicle metabolism in culture. PMID- 27683267 TI - Effects of Daily Exposure to Saccharin and Sucrose on Testicular Biologic Functions in Mice. AB - Saccharin sodium consumption is considered safe and beneficial, owing to its very intense sweetness without any associated calories, but supporting scientific data remain sparse and controversial. Herein, we demonstrate that dose-response relationships existed with regard to administration of saccharin or sucrose to mice for 35 days, and this association involved testis-expressed sweet-tasting molecules (taste receptor type 1 subunit 3 [T1R3]; G protein alpha-gustducin [Galpha]). Mouse body weights and testis weights in middle- and low-dose saccharin-treated groups were increased with up-expressions of molecules involved in testicular sweet taste and steroidogenic (middle saccharin: steroidogenic acute regulatory protein [StAR]; P450 cholesterol side-chain cleavage enzyme [CYP11A1]; 17-alpha-hydroxylase/C17,20-lyase [CYP17A1]; low saccharin: StAR). Moreover, a high-dose saccharin-related decline in reproductive hormone levels and injuries to testis and sperm were observed to be associated with suppression of testicular T1R3 and Galpha, as well as steroidogenic-related factors (StAR; 3 beta-hydroxysteroid dehydrogenase [3-beta-HSD]; CYP11A1; CYP17A1; 17-beta hydroxysteroid dehydrogenase [17-beta-HSD]), and activation of cleaved caspase-3. However, abnormalities of the testis and sperm in high- and middle-dose sucrose exposed mice were related to the increased-cleaved caspase-3, but independent of T1R3 and/or Galpha. Collectively, our results clearly suggest that saccharin induced physiologic effects on testis are associated with testicular T1R3 and Galpha, which differed from sucrose. We hence call for a reassessment of the excessive use of sweeteners in daily life, especially artificial ones, considering their potential side effects. PMID- 27683268 TI - Risk factors for post-partum hemorrhage following vacuum assisted vaginal delivery. AB - OBJECTIVE: To identify risk factors for post-partum hemorrhage (PPH) following vacuum assisted vaginal delivery (VAVD). STUDY DESIGN: A retrospective study of all women with singleton pregnancies who underwent VAVD in a tertiary hospital (2012-2014). PPH was defined as any of the following: >=500 ml estimated blood loss, hemoglobin drop >=3 g/dl (difference between pre- and post-VAVD hemoglobin levels) or the need for blood products transfusion. Characteristics of women with PPH following VAVD were compared to those of women with no PPH following VAVD. RESULTS: Of 1,154 VAVDs, 295 (25.6 %) had PPH. Women in the PPH group were more often nulliparous (83.1 vs. 70.5 %, p = 0.001) and had higher rate of hypertensive disorders (4.4 vs. 1.4 %, p = 0.001). The rate of episiotomy (87.8 vs. 81.6 %, p = 0.01) was higher in the PPH group. In multivariate analysis, risk factors for PPH were (Odds Ratio, 95 % Confidence Interval) hypertensive disorders (2.40, 1.03-5.58, p = 0.04), induction of labor (1.42, 1.01-2.10, p = 0.04) and longer second (1.003, 1.001-1.006, p = 0.03) and 3rd (1.02, 1.01-1.04, p = 0.004) stages of labor. CONCLUSION: Risk factors for PPH following VAVD can be identified and should be taken into consideration at the immediate post-partum period. PMID- 27683269 TI - Identification of genetic variation in the lncRNA HOTAIR associated with HPV16 related cervical cancer pathogenesis. AB - PURPOSE: Previously, over-expression of the long noncoding RNA (lncRNA) HOTAIR has been found to be associated with the invasive and metastatic capacities of several epithelial cancers, including cervical cancer (CaCx). Here, we aimed at identifying functionally relevant genetic variants that may be employed to differentiate between clinically distinct CaCx subtypes, i.e., those exhibiting high HOTAIR levels and molecular signatures of metastasis and those lacking such signatures in the presence of low HOTAIR expression levels. METHODS: Genomic DNA isolated from various cervical tissue samples (characterized by histopathology and HPV status) was used for HOTAIR amplicon sequencing, followed by validation of the findings by Sanger sequencing. The impact of the genetic variants found on the secondary structure of HOTAIR and the concomitant alterations in miRNA binding sites were determined through in silico analysis, followed by miRNA expression analysis by quantitative real-time PCR and confirmation of miRNA binding using a luciferase reporter assay. RESULTS: We found that rs2366152C was over-represented [ORage-adjusted = 2.58 (1.23-5.57); p = 0.014] in low HOTAIR expressing HPV positive CaCx cases compared to HPV negative controls. This genetic variant showed the propensity of a secondary structure alteration and gain of a miR-22 binding site in HOTAIR, which was found to be concordant with miR-22 over-expression in low HOTAIR CaCx cases compared to controls. We found that miR-22 expression negatively correlated with HOTAIR and E7 expression in HPV16 positive cases and in an E7 transfected HPV negative CaCx-derived cell line (C33A), but was not altered in high HOTAIR cases compared to controls. Reduced luciferase activity of a HOTAIR rs2366152C expression plasmid in C33A cells through miR-22 co-transfection confirmed the ability of miR-22 to specifically target rs2366152C-harbouring HOTAIR lncRNA in CaCx cells, ultimately leading to its down-regulation. CONCLUSIONS: Our data indicate that rs2366152C not only has the potential to serve as a marker for singling out CaCx cases lacking metastatic molecular signatures, but also to explain the functional inactivation of HOTAIR in these cases, including the mechanism of its down-regulation. PMID- 27683270 TI - Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy. AB - Background: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. Methods: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). Results: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. Conclusions: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN. PMID- 27683272 TI - Plasma sodium measurements by direct ion selective methods in laboratory and point of care may not be clinically interchangeable. AB - An estimated 25 % of indirect ion selective electrode (ISE) ICU plasma sodium measurements differ from corresponding direct ISE values by at least 4 mmol/L, the dominant factor being indirect ISE over-estimation driven by hypoproteinemia. Since direct measurements are considered unaffected by protein concentrations, we investigated whether direct ISE plasma sodium measurements in the laboratory and at point of care in ICU show sufficient agreement to be clinically interchangeable. From a 5 year clinical chemistry database, 9910 ICU plasma samples were assessed for agreement between direct ISE sodium measurements in ICU (ABL 700) and in the central laboratory (Vitros Fusion). The relationship between differences in paired plasma sodium measurements (Vitros-ABL) and total plasma protein concentrations was evaluated by generalized estimating equation linear regression. Patients were hypo-proteinemic [mean (SD) total protein concentration 56.9 (9.04) g/L]. Mean (SD) paired Vitros-ABL sodium measurements was -0.087 (1.74) mmol/L, range -14 to +10 mmol/L. Disagreement at >=|4|mmol/L, >=|3|mmol/L and >=|2|mmol/L was present in 409 (4.1 %), 1333 (13.4 %) and 3591 (36.2 %) pairs respectively. Test-retest disagreement estimates within either source alone were substantially lower. Small negative Vitros-ABL differences associated with low plasma protein concentrations were reversed at high protein concentrations. Disagreement between plasma sodium concentrations monitored by two common direct ISE analyzers was substantially less than reported between direct and indirect ISE devices, although a protein influence of low clinical importance persisted. Disagreement was sufficient to jeopardize safe interchangeable interpretation in situations with a low tolerance for imprecision, such as hyponatremia correction. PMID- 27683273 TI - Activation of Checkpoint Kinase Chk1 by Reactive Oxygen Species Resulting from Disruption of wat1/pop3 in Schizosaccharomyces pombe. AB - DNA double-strand breaks are critical lesions that can lead to chromosomal aberrations and genomic instability. In response to DNA damage, Chk1, a serine/threonine kinase, is responsible for cell cycle arrest to prevent damaged cells from progressing through the cell cycle. Here, we report that the disruption of wat1, a WD repeat-containing protein, leads to the phosphorylation of Chk1. The double-deletion of chk1 and wat1 had a grave effect on the survival of fission yeast cells, and the spontaneous recombination rate was also high upon double-deletion of wat1 and chk1, as compared to the single-mutant. In the absence of wat1, the cells exhibited a high level of nuclear fragmentation that resulted in the accumulation of Rad22 yellow fluorescent protein foci. Furthermore, we show that wat1 is required for the regulation of the oxidative stress response. We observed elevated levels of reactive oxygen species (ROS) generation in wat1-null mutant that led to a high degree of propidium iodide staining at nonpermissive temperature. Based on the results presented here, we hypothesize that ROS production in wat1-null mutant cells generates DNA fragmentation that could trigger a checkpoint response and that, in the absence of checkpoint kinase Chk1, the cells exhibit severe growth defects leading to a synthetic lethal phenotype. PMID- 27683274 TI - Reconstructing Demography and Social Behavior During the Neolithic Expansion from Genomic Diversity Across Island Southeast Asia. AB - Archaeology, linguistics, and increasingly genetics are clarifying how populations moved from mainland Asia, through Island Southeast Asia, and out into the Pacific during the farming revolution. Yet key features of this process remain poorly understood, particularly how social behaviors intersected with demographic drivers to create the patterns of genomic diversity observed across Island Southeast Asia today. Such questions are ripe for computer modeling. Here, we construct an agent-based model to simulate human mobility across Island Southeast Asia from the Neolithic period to the present, with a special focus on interactions between individuals with Asian, Papuan, and mixed Asian-Papuan ancestry. Incorporating key features of the region, including its complex geography (islands and sea), demographic drivers (fecundity and migration), and social behaviors (marriage preferences), the model simultaneously tracks a full suite of genomic markers (autosomes, X chromosome, mitochondrial DNA, and Y chromosome). Using Bayesian inference, model parameters were determined that produce simulations that closely resemble the admixture profiles of 2299 individuals from 84 populations across Island Southeast Asia. The results highlight that greater propensity to migrate and elevated birth rates are related drivers behind the expansion of individuals with Asian ancestry relative to individuals with Papuan ancestry, that offspring preferentially resulted from marriages between Asian women and Papuan men, and that in contrast to current thinking, individuals with Asian ancestry were likely distributed across large parts of western Island Southeast Asia before the Neolithic expansion. PMID- 27683276 TI - Direct oral anticoagulants in the elderly: systematic review and meta-analysis of evidence, current and future directions. AB - BACKGROUND: Concerns regarding the use of direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban, rivaroxaban) in the elderly persist owing to the lack of randomised controlled trials targeting this age group. OBJECTIVES: The aim of this study was to assess the efficacy and safety of DOACs in elderly patients (aged 75 years or more) with atrial fibrillation or venous thromboembolism (VTE), based on already published large randomised trials. METHODS: EMBASE, MEDLINE and the Cochrane Library were searched from inception to June 2015 for phase III trials. Pooled odds ratios with 95% confidence intervals were calculated for the target population using the fixed effect model. Heterogeneity between trials was assessed using the I2 Higgins test. RESULTS: A total of 30 655 participants aged 75 or older from eight studies (two apixaban, one dabigatran, two edoxaban, three rivaroxaban) were included in the statistical evaluation. Pooled analysis revealed that treatment with a DOAC was associated with a statistically significant odds reduction for stroke and embolism in elderly patients with atrial fibrillation. Also, DOACs significantly reduced the number of recurrent VTE events or VTE-related deaths in the participants aged 75 years or more with VTE. There was no statistically significant difference in safety outcome for both indications with DOAC compared with vitamin K antagonists although some differences in safety profiles between the DOACs were apparent. CONCLUSION: DOACs show the same or greater efficacy than vitamin K antagonists in elderly patients with atrial fibrillation and VTE. Individual differences between DOACs in terms of safety profile cannot be excluded on the basis of current evidence. Direct head-to-head comparisons are needed to investigate possible divergence in pharmacological profiles between DOACs. Additionally, further studies conducted in real-word settings and in the frail elderly are ongoing and it would be interesting to target this particular patient group. PMID- 27683275 TI - Short-Term Memory Effects on Crossing the Boundary: Discrimination between Large and Small Quantities in Angelfish (Pterophyllum scalare). AB - Rudimentary quantification abilities are found in numerous animal species and in human infants all demonstrating the ability to discriminate between quantities differing in numerical size. An open question is whether individuals rely on different underlying systems to discriminate between large (analogue magnitude system (AMS) for number of items exceeding 3) and small quantities (object-file system (OFS) for number of items below 4), or they use only one system (AMS) for the entire number range. The two-system hypothesis has been supported by finding reduced ability to discriminate between quantities that cross the large-small boundary in several species. Recently, the role of cognitive representation, i.e., memory, in quantity discrimination has also been recognized. Here, we investigated whether angelfish can discriminate quantities across the boundary under two memory conditions. In a binary choice test, single angelfish were allowed to see groups (shoals) of conspecifics of different numerical size on the two sides of their test tank. In Experiment 1, their choice was recorded after a 2-sec retention interval during which shoal size information was unavailable. Angelfish were able to discriminate the larger shoal across the boundary when the shoals differed by a 2:1 or higher ratio, but not when the ratio was lower. In Experiment 2, however, with a 15-sec retention interval, angelfish could only detect a four-fold difference in ratio but failed to detect a three- or a two fold difference across the boundary. These results suggest that angelfish can remember smaller differences for a short (2 sec) but not for a longer (15 sec) period. Together with previous findings, the current results support the idea that angelfish use two distinct systems for representing quantity, but they may recruit the AMS even for the small number range under some circumstances, e.g., when higher memory demand is imposed by a greater retention interval. PMID- 27683277 TI - Peripheral Blood Leukocyte Production of BDNF following Mitogen Stimulation in Early Onset and Regressive Autism. AB - Brain-derived neurotrophic factor (BDNF) is critical for neuronal differentiation and synaptic development. BDNF is also implicated in the development of psychological disorders including depression, bipolar disorder and schizophrenia. Previously, elevated BDNF levels were observed in neonatal blood samples from infants who were later diagnosed with autism when compared with children who developed normally, suggesting that BDNF may be involved in the development of autism. BDNF is produced by activated brain microglial cells, a cellular phenotype that shares several features with peripheral macrophages, suggesting an important role for the immune system in BDNF production. We hypothesized that under mitogenic stimulation, peripheral blood mononuclear cells obtained from children with autism may have altered BDNF production compared with age-matched typically developing control subjects. In addition, we examined the differences between the production of BDNF in classic/early-onset autism and children who had a regressive form of autism. We show here that plasma levels of BDNF levels are increased in children with autism, especially in early onset autism subjects. Furthermore, under mitogenic stimulation with PHA and LPS, BDNF production is significantly increased in children with autism compared with typically developing subjects. However, stimulation with tetanus toxoid results in a decreased response in children with autism. This data suggest that immune cell derived production of BDNF could be an important source for the increased BDNF that is detected in some subjects with autism. As a neurotrophic factor produced by immune cells, BDNF could help elucidate the role of the immune system in neurodevelopment and neuronal maintenance, which may be dysregulated in autism. PMID- 27683278 TI - First Report of the Human-Pathogenic Enterocytozoon bieneusi from Red-Bellied Tree Squirrels (Callosciurus erythraeus) in Sichuan, China. AB - Enterocytozoon bieneusi is a common opportunistic pathogen causing diarrhea and enteric disease in a variety of animal hosts. Although it has been reported in many animals, there is no published information available on the occurrence of E. bieneusi in red-bellied tree squirrels. To understand the occurrence, genetic diversity, and zoonotic potential of E. bieneusi in red-bellied tree squirrels, 144 fecal specimens from Sichuan province, China, were examined by PCR amplification and sequencing of the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene of E. bieneusi. The overall infection rate of E. bieneusi 16.7% (24/144) was observed in red-bellied tree squirrels. Altogether five genotypes of E. bieneusi were identified: three known genotypes D (n = 18), EbpC (n = 3), SC02 (n = 1) and two novel genotypes CE01, CE02 (one each). Multilocus sequence typing (MLST) analysis employing three microsatellite (MS1, MS3, MS7) and one minisatellite (MS4) revealed 16, 14, 7 and 14 positive specimens were successfully sequenced, and identified eight, three, three and two genotypes at four loci, respectively. In phylogenetic analysis, the three known genotypes D, EbpC, and SC02 were clustered into group 1 with zoonotic potential, and the two novel genotypes CE01 and CE02 were clustered into group 6. The present study firstly reported the occurrence of E. bieneusi in red-bellied tree squirrels in China, and the E. bieneusi genotypes D and EbpC were found in humans previously. These results indicate that red-bellied tree squirrels may play a potential role in the transmission of E. bieneusi to humans. PMID- 27683279 TI - High extent of O-GlcNAcylation in breast cancer cells correlates with the levels of HAS enzymes, accumulation of hyaluronan, and poor outcome. AB - PURPOSE: Obesity and oversupply of glucose, e.g., due to nutritional factors may shape the tumor microenvironment favorable for tumor progression. O GlcNAcylation, a reversible modification of intracellular proteins, influences on several cellular functions and is connected to many diseases including cancer. Glycosaminoglycan hyaluronan (HA) enhances tumor progression and in breast cancer HA accumulation associates strongly with poor outcome. In vitro studies have suggested that O-GlcNAcylation may enhance HA synthesis. The aim of this study was to investigate the correlations between O-GlcNAcylation, HA-related parameters, and disease outcome in a clinical breast cancer material consisting of 278 breast cancer cases. METHODS: In microscopic analyses, O-GlcNAc staining of the breast carcinoma cells was evaluated in several randomly picked high-power fields of each section. The extent of cytoplasmic O-GlcNAc staining was graded as either low or high according to the intensity of the staining and the percentage of stained cells. The extent of nuclear O-GlcNAc staining was categorized as either low or high according to the percentage of stained nuclei. RESULTS: A high extent of both cytoplasmic and nuclear O-GlcNAcylation correlated with an increased relapse rate, development of distant metastases, and poor outcome. A high extent of cytoplasmic O-GlcNAcylation correlated also with the accumulation of all hyaluronan synthase (HAS1-3) proteins and with a large amount of HA in the tumor stroma. In addition, a high extent of nuclear O-GlcNAcylation associated with obesity. CONCLUSIONS: The results suggest a mechanistic association between increased O-GlcNAcylation and HA synthesis, leading to a HA-rich microenvironment favorable for breast cancer progression. PMID- 27683280 TI - The prognosis of women diagnosed with breast cancer before, during and after pregnancy: a meta-analysis. AB - OBJECTIVE: Previous meta-analyses have examined the prognosis of women with pregnancy-associated breast cancer (PABC) as well as pregnancy that follows breast cancer diagnosis. Since then, many additional studies have been performed. We conducted an updated meta-analysis to examine the prognosis for women who become pregnant before, during and after a diagnosis of breast cancer. We also performed analyses on the various subgroups within PABC such as pregnancy and postpartum cases, as well as on time periods postpartum. METHODS: We identified studies that reported on overall (OS) and disease-free survival (DFS) in patients diagnosed with breast cancer during pregnancy or up to 5 years postpartum from four electronic databases. We also identified studies that reported on OS and DFS where pregnancy up to 5 years occurred after a breast cancer diagnosis. RESULTS: 41 studies met our inclusion criteria (cases = 4929; controls = 61,041) for pregnancy occurring during or before breast cancer diagnosis. There was an overall increased risk of death amongst patients compared to non-pregnant controls [HR 1.57; 95 % CI 1.35-1.82]. Subgroup analysis indicated poor survival outcomes for those diagnosed either during pregnancy or postpartum (PABC) [HR 1.46; 95 % CI 1.17-1.82] as well as those diagnosed during pregnancy alone [HR 1.47; 95 % CI 1.04-2.08]. Those diagnosed postpartum had the poorest overall survival [HR 1.79; 95 % CI 1.39-2.29]. Similarly, patients with PABC had decreased DFS compared to controls [HR 1.51; 95 % CI 1.22-1.88]. Those diagnosed postpartum were the most at risk of disease progression or relapse [HR 1.86; 95 % CI 1.17-2.93]. 19 studies met our inclusion criteria (cases = 1829; controls = 21,907) for pregnancy following breast cancer diagnosis. Such women had a significantly reduced risk of death compared to those who did not become pregnant [pHR 0.63; 95 % CI 0.51-0.79]. A subgroup analysis to account for the "healthy mother effect" generated similar results [pHR 0.65; 95 % CI 0.52-0.81]. CONCLUSION: Pregnancy that occurs before or concurrently with a diagnosis of breast cancer is more likely to result in death and decreased disease-free survival. On the other hand, pregnancy occurring after a breast cancer diagnosis reduces the risk of death. PMID- 27683283 TI - Duration of untreated psychosis in an Egyptian sample: Sociodemographic and clinical variables. AB - BACKGROUND: Duration of untreated psychosis (DUP) has been considered as a poor prognostic factor for psychotic disorder. Several studies have been investigating different predictors of DUP in Western countries, while in Egypt only a few studies have examined various predictors of DUP. AIMS: To study DUP in Egyptian patients with psychotic disorders and to investigate how certain illnesses, patient, socio-cultural risk factors and help-seeking behaviour are correlated with prolonged DUP. METHOD: The sample included 100 patients with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) diagnosis of psychotic disorder were selected and interviewed to assess DUP. They were interviewed using the Structured Clinical Interview for DSM-IV axis I disorders (SCID-I), Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scale. RESULTS: Mean (+/-standard deviation ( SD)) of DUP was found to be 36.93(+/-45.27) months. DUP was correlated with various sociodemographic and clinical variables. Following log transformation of DUP, correlation with PANSS scores was done and revealed highly significant statistical relation of DUP to PANSS negative and PANSS positive scores. In linear regression analysis, it was found that age of patients, the age of onset, residence, being illiterate, the insidious mode of onset, negative family history of psychiatric disorder and the severity of illness as indicated by PANSS are among DUP predictors. CONCLUSION: Longer DUP results from multiple patient- and illness-related factors. This has many implications in targeting early intervention with specific consideration to cultural factors. PMID- 27683281 TI - Prediction of coronary artery calcium progression by FDG uptake of large arteries in asymptomatic individuals. AB - PURPOSE: The purpose of this study is to evaluate whether fluorodeoxyglucose (FDG) uptake of the large arteries can predict coronary artery calcium (CAC) progression in asymptomatic individuals. METHODS: Ninety-six asymptomatic individuals who underwent FDG positron emission tomography (PET) and CAC scoring on the same day for health screening and follow-up CAC scoring >=1 year after baseline studies (mean 4.3 years) were included. Vascular FDG uptake was measured and corrected for blood pool activity to obtain peak and average target-to-blood pool ratios (TBRpeak and TBRavg, respectively) for the carotid arteries, and ascending and abdominal aorta. CAC scores at baseline and follow-up of each individual were measured and absolute CAC change (DeltaCAC), annual CAC change (DeltaCAC/year), and annual CAC change rate (DeltaCAC%/year) were calculated. CAC progression was defined as DeltaCAC >0 for individuals with negative baseline CAC; DeltaCAC/year >=10 for those with baseline CAC of 0=10 % for those with baseline CAC >=100. Vascular FDG uptake and other clinical risk factors were compared between CAC-progressors and non-CAC-progressors. Multivariate analysis was performed to evaluate whether vascular FDG uptake can independently predict CAC progression. RESULTS: Thirty-one subjects showed CAC progression. CAC-progressors showed significantly higher TBRpeak and TBRavg as compared to non-CAC-progressors for all three arteries. TBRpeak of the abdominal aorta was significantly associated with CAC progression in multivariate analysis, with age and baseline CAC. A higher TBRpeak of the abdominal aorta (>=2.11) was associated with CAC progression among subjects with negative baseline CAC only. In subjects with positive baseline CAC, only the amount of baseline CAC was significantly associated with CAC progression. However, the positive predictive value of the TBRpeak of the abdominal aorta was <40 % when age was <58 or baseline CAC was negative. CONCLUSIONS: Higher FDG uptake of the large arteries is associated with an increased risk of CAC progression in asymptomatic subjects with negative baseline CAC. But its clinical application needs further validation. PMID- 27683282 TI - Comparison of 300,000 and 600,000 IU Oral Vitamin-D Bolus for Vitamin-D Deficiency in Young Children. AB - OBJECTIVE: To compare the efficacy and safety of 300,000 and 600,000 IU vitamin-D single-oral dose for the treatment of vitamin-D deficiency (VDD) in young children (3 mo - 3 y). METHODS: This double-blind randomized control trial (Clinical Trail Registration-CTRI/2012/05/002621) was conducted in the Pediatric out-patient department (OPD) at a tertiary-care referral hospital. Children (3 mo - 3 y) with clinical/radiological features suggestive of VDD were screened; those found to be having 25(OH)D below 15 ng/ml and meeting inclusion and exclusion criteria's were enrolled after taking informed consent. They were randomized into two groups, one receiving 600,000 and other 300,000 IU vitamin-D orally stat (Stoss-therapy). Primary outcome measure was proportion of children developing hypercalcemia/and hypercalciuria at day 7-10 post-therapy. Secondary outcome measures were proportion of children with hypercalciuria at day 3-5, hypercalcemia/and hypercalciuria at day 25-30 and 25(OH)D sufficiency at day 25 30 post-therapy. RESULTS: Sixty children, 30 in each group were randomized to two study groups. Baseline variables were comparable in two groups. Primary outcome measure (proportion of children with hypercalcemia/and hypercalciuria at 7 - 10th d) were 18.5 % (5/27) in 600,000 and 10.7 % (3/28) in 300,000 IU group (P = 0.47). Secondary outcome measures were - i) Proportion of children with hypercalciuria (3-5th d) were 18.5 % (5/27) in 600,000 and 7 % (2/28) in 300,000 group (P = 0.25). ii) Proportion of children with hypercalcemia/and hypercalciuria (25-30th d) were 18.5 % (5/27) in 600,000 and 11 % (3/28) in 300,000 group (P = 0.47). iii) All children in both groups had 25(OH)D levels in sufficiency range (25-30th d). With this sample size no significant difference in any of the group could be established. CONCLUSIONS: The superiority of 300,000 over 600,000 IU vitamin-D single-dose oral therapy for VDD in children (3 mo - 3 y) in terms of safety could not be established with this sample size, although the prevalence of hypercalcemia/and hypercalciuria was observed more with 600,000 IU group. Both the regimens were effective for treating VDD at 25-30th d post therapy. PMID- 27683284 TI - 1. Prenatal Diagnosis of Chromosomal Disorders - Molecular Aspects. PMID- 27683286 TI - 3. Risk Assessment. PMID- 27683285 TI - 2. Post-Natal Molecular Diagnosis of Inherited Diseases. PMID- 27683287 TI - 4. Global Approach to Biomedicine: Functional Genomics and Proteomics. PMID- 27683288 TI - 5. Pharmacogenomics and Personalized Medicine. PMID- 27683289 TI - 6. Dose Adjustments Based on Pharmacogenetics of CYP450 Enzymes. PMID- 27683290 TI - 7. Pharmacogenetics of Drug Receptors. PMID- 27683291 TI - 8. Application of Pharmacogenetics in Dose Individualization in Diabetes, Psychiatry, Cancer and Cardiology. PMID- 27683292 TI - 9. Point-of-Care Molecular Diagnosis: A Near Future? PMID- 27683295 TI - 12. Ethics and Legal Issue of Genetic Testing. PMID- 27683294 TI - 11. European Quality Assessment Networks in Molecular Diagnostics. PMID- 27683293 TI - 10. Circulating Nucleic Acids as Diagnostic Tool. PMID- 27683296 TI - Glossary: Definitions Useful in Understanding Pharmacogenetics. PMID- 27683298 TI - Cluster Correspondence Analysis. AB - A method is proposed that combines dimension reduction and cluster analysis for categorical data by simultaneously assigning individuals to clusters and optimal scaling values to categories in such a way that a single between variance maximization objective is achieved. In a unified framework, a brief review of alternative methods is provided and we show that the proposed method is equivalent to GROUPALS applied to categorical data. Performance of the methods is appraised by means of a simulation study. The results of the joint dimension reduction and clustering methods are compared with the so-called tandem approach, a sequential analysis of dimension reduction followed by cluster analysis. The tandem approach is conjectured to perform worse when variables are added that are unrelated to the cluster structure. Our simulation study confirms this conjecture. Moreover, the results of the simulation study indicate that the proposed method also consistently outperforms alternative joint dimension reduction and clustering methods. PMID- 27683297 TI - Immediate versus delayed aggressive physical therapy following buccal fat pad interposition in oral submucous fibrosis-a prospective study in Central India. AB - PURPOSE: Oral submucous fibrosis is a disease of an Indian subcontinent with obscure aetiology and poorly treated with varying signs and symptoms. OSMF occurs at any age but is most commonly seen in teenagers and adults in the age ranging between 16 and 35 years. A number of surgical treatments have been used for the treatment of oral submucous fibrosis with unpredictable results. PATIENTS AND METHOD: In this study, 220 patients were randomly divided into two groups with mouth opening less than 16 mm and evaluated with immediate and delayed aggressive physiotherapy with buccal fat pad interposition after fibrotomy. Group A (n = 110) patients underwent aggressive mouth opening exercise from the next postoperative day while in group B (n = 110), patients underwent physiotherapy 7th day postoperatively. Pain and discomfort, mucosalization, infection, flap dehiscence and necrosis were noted. Patients were followed for 1 year on a regular interval basis. RESULTS: At the end of 1-year follow up, the post operative mean mouth opening in group A was 38.63 mm and 34.19 mm in group B. In group A, the immediate physiotherapy results in mild to moderate pain and discomfort to the patients as compared to no apparent pain in the group B. The mean mucosalization time in group A and group B was 4.2 and 5.1 weeks, respectively. Postoperatively, all patients achieve satisfactory mouth opening. CONCLUSION: Immediate aggressive physiotherapy yields a comparatively superior result than delayed physiotherapy with respect to mouth opening in 1 year of follow-up. PMID- 27683299 TI - The one-leg standing radiograph: An improved technique to evaluate the severity of knee osteoarthritis. AB - OBJECTIVES: The purpose of this study was to compare the joint space width between one-leg and both-legs standing radiographs in order to diagnose a primary osteoarthritis of the knee. METHODS: Digital radiographs of 100 medial osteoarthritic knees in 50 patients were performed. The patients had undergone one-leg standing anteroposterior (AP) views by standing on the affected leg while a both-legs standing AP view was undertaken while standing on both legs. The severity of the osteoarthritis was evaluated using the joint space width and Kellgren-Lawrence (KL) radiographic classification. The t-test was used for statistical analysis. RESULTS: The mean medial joint space width found in the one leg and in the both-legs standing view were measured at 1.8 mm and 2.4 mm, respectively (p < 0.001, 95% CI 0.5 to 0.7). 33%, 47.4% and 23.1% of the knees diagnosed with a KL grade of I, II and III in the both-legs standing views were changed to KL grade II, III and IV in the one-leg standing views, respectively. No changes for KL IV osteoarthritis diagnoses have been found between both- and one-leg standing views. CONCLUSIONS: One-leg standing radiographs better represent joint space width than both-legs standing radiographs. 32% of both-legs standing radiographs have changed the KL grading to a more severe grade than that in the one-leg standing radiographs.Cite this article: P. Pinsornsak, K. Naratrikun, S. Kanitnate, T. Sangkomkamhang. The one-leg standing radiograph: An improved technique to evaluate the severity of knee osteoarthritis. Bone Joint Res 2016;5:436-441. DOI: 10.1302/2046-3758.59.BJR-2016-0049.R1. PMID- 27683300 TI - Catamnesis results of an inpatient neuro-otologic and psychosomatic tinnitus therapy 1-5 years after discharge. AB - Treating tinnitus with the resources offered in hospitals can become necessary for patients suffering from complex tinnitus if a high symptom severity, usually accompanied by a corresponding psychosomatic comorbidity, is present. For such costly therapies, for example, the neuro-otologic psychosomatic tinnitus therapy (NPT) examined here, the long-term effect is particularly important; however, reliable catamnesis studies for inpatient treatments are not yet available. Data from 169 (from a total of 327 contacted) inpatients suffering from complex tinnitus were analysed here. To assess the tinnitus stress, the Mini-Tinnitus Questionnaire (Mini-TF12-In German language) according to Hiller and Goebel [1], and for the assessment of the anxiety and depression element, the German version of the Hospitality Anxiety and Depression Score (HADS) [2] were analysed at the start of the therapy, at the end of the therapy and at the earliest 1 year (up to 5 years) after discharge from inpatient treatment. The data were correlated with the current hearing status. In addition, the subjectively perceived effect factors of the therapy as well as the therapies continued outside of hospital were queried. On average, the therapy lasted 39.3 days (SD 13.6) = 5.6 weeks, and the mean of the follow-up time was 38.5 months (12-70 months) (SD 18). The therapy focused on daily neuro-otologic counselling, the improvement of the concrete hearing ability, an audio-therapy as well as frequent individual and group psychotherapy based on neuro-otology. 53.8 % of patients experienced relevant hearing loss (according to WHO criteria) which needed to be treated in addition to tinnitus. Both at the end of the therapy and the follow-up consultation, a significant improvement of the tinnitus stress and a continuing significant improvement of the depression and anxiety element could be achieved in the HADS with high effect levels ranging from 1 to 2.5. Patients who did not improve (n = 7) or even deteriorated (n = 2) demonstrated increased hearing impairment, requiring hearing aids. During the therapy, particularly, the neuro otologic counselling, the psychotherapy, and the audio-therapy were experienced as effective. After discharge from hospital, especially, the progressive muscle relaxation according to Jacobsen was continued, as well as psychotherapy. With the corresponding symptomatic suffering, an inpatient hospitalisation and tinnitus therapy with neuro-otologic and psychosomatic alignment can achieve medium-to-high-grade therapeutic effects. This requires a disorder-specific approach, which also includes the elements of neuro-otologic counselling, psychotherapy as well as audio-therapy, and the possibility of providing hearing aids and an approach which aims at the continuation of the therapies experienced as helpful. PMID- 27683303 TI - eJIFCC Special Issue on Laboratory Reference Intervals. PMID- 27683301 TI - Double nasoseptal flap technique for endonasal pituitary surgery. AB - Endoscopic endonasal approach has been successfully used for the management of pituitary tumors; however, the loss of septal mucosa especially around sphenoethmoidal recess and posterior nasal septum might be a disadvantage of this technique. The aim of this study is to describe a variation of the endonasal approach, "double nasoseptal flap" technique in endoscopic transsphenoidal pituitary surgery, and to evaluate its outcomes. The technique depends on fully harvested bigger nasoseptal flap on one side and smaller on the other. Thirty patients were included. Functional results were assessed by preoperative and postoperative first month visual analogue scale (VAS), and morphology was evaluated by achieving intact septum from the sphenoid ostium to the columella. Sphenoid sinusitis, the presence of synechia and crusting in the sphenoethmoidal recess was also assessed. Mean VAS was 71 and 67 mm preoperatively and postoperatively, respectively (p > 0.01). There were no septal perforations, synechia, and sphenoid sinusitis postoperatively. Three patients had (10 %) crusts on sphenoethmoidal recess on first month postoperatively. Double nasoseptal flap technique has advantages, such as wider exposure during surgery; prepared flaps could be used if needed, better morphological and functional outcomes postoperatively. The technique is safe without any perforations and minimal crusting. PMID- 27683304 TI - Reference Intervals: Practical Aspects. PMID- 27683302 TI - Creative ways to well-being: Reappraisal inventiveness in the context of anger evoking situations. AB - Neuroscientific studies in the field of creativity mainly focused on tasks drawing on basic verbal divergent thinking demands. This study took a step further by investigating brain mechanisms in response to other types of creative behavior, involving more "real-life" creativity demands in the context of emotion regulation and well-being. Specifically, functional patterns of EEG alpha activity were investigated while participants were required to generate as many and as different ways as possible to reappraise presented anger-eliciting situations in a manner that reduces their anger. Cognitive reappraisal involves some of the same cognitive processes as in conventional verbal creativity tasks, inasmuch as it requires an individual to inhibit or disengage from an emotional event, to shift attention between different perspectives, and to flexibly adopt new solutions. To examine whether alpha oscillations during cognitive reappraisal are different from those during conventional creative ideation, the EEG was also assessed during performance of the Alternative Uses task, requiring individuals to generate as many and as original uses of an object as possible. While cognitive reappraisal was associated with a similar pattern of alpha power as observed in conventional verbal creative ideation, the former yielded significantly stronger alpha power increases at prefrontal sites, along with lower alpha increases at more posterior cortical sites, indicating higher cognitive control and less spontaneous imaginative thought processes in the generation of effective strategies to regulate an ongoing negative emotional state. PMID- 27683305 TI - "Are my Laboratory Results Normal?" Considerations to be Made Concerning Reference Intervals and Decision Limits. AB - This paper looks at the topic of reference intervals from the point of view of the patient or the clinician. The differences between the concepts of reference intervals (biological characteristic of a well defined population) and the various types of decision limits are illustrated and discussed. Decision limits can be defined in different ways: based on a Bayesian approach, on epidemiological studies or on clinical experience, but differ from reference intervals because, while the latter deals with physiology, decision limits are related to some kind of disease or risk of developing it. PMID- 27683306 TI - 3. Pediatric Reference Intervals: Critical Gap Analysis and Establishment of a National Initiative. PMID- 27683308 TI - Accurate Reference Intervals are Required for Accurate Diagnosis and Monitoring of Patients. PMID- 27683307 TI - Bone Health in Childhood: Usefulness of Biochemical Biomarkers. AB - Development of the human skeleton begins in early embryonic life and continues through childhood into early adulthood. The acquisition of peak bone mass during these vulnerable periods may impact on skeletal fragility in later adult years. Once the skeleton has reached maturity, bone remodelling continues with periodic replacement of old bone with new at the same location. Bone biomarkers are specifically derived biomarkers that reflect both formation by osteoblasts and resorption by osteoclasts. Children have significantly higher concentrations of bone biomarkers than adults due to both skeletal growth and rapid bone turnover during childhood and adolescence. Biochemical assessment of markers of bone turnover may be important in the diagnosis, prognosis and management of metabolic bone disease. This review will discuss the various serum bone markers used for assessing bone health and the factors that influence their utility. PMID- 27683309 TI - You Are What you Eat: a Metabolomics Approach to Understanding Prey Responses to Diet-Dependent Chemical Cues Released by Predators. AB - Prey responses to predator cues are graded in intensity in accordance with the degree of threat presented by the predator. In systems in which prey gather information on predators by using chemicals, prey often respond more to the odor of predators that have consumed conspecifics, as opposed to heterospecifics. We investigated the response of a prey species, the mud crab, Panopeus herbstii, to urine of blue crab, Callinectes sapidus, fed mud crabs or oysters. Behavioral analysis was combined with metabolomics to characterize bioactive deterrents in the urine of predators fed different diets. Urine from blue crabs fed oysters or mud crabs depressed mud crab foraging when presented singly, with the urine derived from a mud crab diet being more potent. The magnitude of foraging depression increased with urine concentration. When urine from blue crabs fed oysters or mud crabs was combined, response to the urine mixture was no different from that to urine derived only from a mud crab diet. Metabolomics analysis indicated diet-dependent differences were related to a set of shared spectral features that differed in concentration in the respective urines, likely consisting of aromatic compounds, amino acids, and lipids. Taken together, these results suggest mud crabs distinguish diet of, and therefore the risk imposed by, predators through detection of a suite of compounds that together represent what the predator has recently consumed. PMID- 27683312 TI - Proteomics - A New Approach in Biomedical Studies. PMID- 27683310 TI - Mice lacking sialyltransferase ST3Gal-II develop late-onset obesity and insulin resistance. AB - Sialyltransferases are a family of 20 gene products in mice and humans that transfer sialic acid from its activated precursor, CMP-sialic acid, to the terminus of glycoprotein and glycolipid acceptors. ST3Gal-II (coded by the St3gal2 gene) transfers sialic acid preferentially to the three positions of galactose on the Galbeta1-3GalNAc terminus of gangliosides GM1 and GD1b to synthesize GD1a and GT1b, respectively. Mice with a targeted disruption of St3gal2 unexpectedly displayed late-onset obesity and insulin resistance. At 3 months of age, St3gal2-null mice were the same weight as their wild type (WT) counterparts, but by 13 months on standard chow they were visibly obese, 22% heavier and with 37% greater fat/lean ratio than WT mice. St3gal2-null mice became hyperglycemic and displayed impaired glucose tolerance by 9 months of age. They had sharply reduced insulin responsiveness despite equivalent pancreatic islet morphology. Analyses of insulin receptor (IR) tyrosine kinase substrate IRS 1 and downstream target Akt revealed decreased insulin-induced phosphorylation in adipose tissue but not liver or skeletal muscle of St3gal2-null mice. Thin-layer chromatography and mass spectrometry revealed altered ganglioside profiles in the adipose tissue of St3gal2-null mice compared to WT littermates. Metabolically, St3gal2-null mice display a reduced respiratory exchange ratio compared to WT mice, indicating a preference for lipid oxidation as an energy source. Despite their altered metabolism, St3gal2-null mice were hyperactive. We conclude that altered ganglioside expression in adipose tissue results in diminished IR sensitivity and late-onset obesity. PMID- 27683313 TI - Applications of Two-Dimensional Electrophoresis Technology to the Study of Atherosclerosis. AB - Atherosclerosis is a multifactorial disease in which hypertension, diabetes, hyperlipidemia and other risk factors are thought to play a role. However, the molecular processes underlying plaque formation and progression are not yet completely known. In the last years some researchers applied proteomics technologies for the comprehension of biochemical pathways of atherogenesis and to search new cardiovascular biomarkers to be utilized either as early diagnostic traits or as targets for new drug therapies. Due to its intrinsic complexity, the problem has been approached by different strategies, all of which have some limitations. In this review, we summarize the most common critical experimental variables in two-dimensional electrophoresis-based techniques and recent data obtained by applying proteomic approaches in the study of atherosclerosis. PMID- 27683314 TI - Multi-Marker Approach with the Use of Biochip Cardiac Array Technology for Early Diagnosis in Patients with Acute Coronary Syndromes. AB - INTRODUCTION: Diagnosis of acute coronary syndrome (ACS) is frequently a challenging task while immediate risk stratification remains crucial for the prompt implementation of appropriate therapy in this setting. The prolonged release pattern of both CK-MB mass and cardiac troponins makes it difficult to identify the origin of recent chest pain, thus a combination of early and later biomarkers might further facilitate the differential diagnosis. The study was designed to evaluate the efficacy of multi-marker approach using biochip array technology in identifying ACS shortly after the symptom onset. MATERIAL AND METHODS: The study group consisted of 42 patients suspected for ACS. Subjects were diagnosed as presenting with unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI). Biomarkers in the serum were determined twice: on admission (<=6 hours from the chest pain onset) and after next 6 hours. Cardiac troponin I was measured by routine sensitive automated assay (STAT cTnI) while other 6 cardiac markers (heart-fatty acid binding protein - H-FABP, myoglobin, glycogen phosphorylase BB, cTn I, CK-MB mass and carbonic anhydrase III) were assessed using biochip array technology. RESULTS: STAT cTnI concentrations within 6 hours from the symptom onset were elevated over the 99(th) percentile for reference population in 83.3% of subjects but none reached the cut-off value for myocardial infarction. Instead, H-FABP demonstrated a very good efficacy in early detection of ACS (90.5%), better than myoglobin and CK-MB mass. Sensitivity of H-FABP calculated for NSTEMI/STEMI subjects reached 100%. The diagnostic efficacy of troponin, myoglobin and CK-MB mass assay markedly increased within 12 hours. It was only for the patients with UA that the cardiac panel was not efficient in the early stratification of risk. CONCLUSIONS: A multi-marker strategy with H-FABP and highly sensitive troponin included enhances the early diagnosis and decision making process in patients with ACS. A new biochip cardiac array technology may serve as a powerful tool for ACS detection in the clinical practice. PMID- 27683316 TI - Polymorphic Variations in 5-HT2A, 5-HTT and DISC 1 in First Episode Schizophrenia Patients. PMID- 27683315 TI - Adiponectin and Metabolic Syndrome in Women at Menopause. AB - Obesity is associated with premature atherosclerosis, as well as with many metabolic alterations including insulin resistance, dyslipidemia and hypertension. Visceral fat accumulation, particularly, is closely associated with the development of metabolic syndrome. The menopause transition, as well as the early postmenopausal period, is associated with increase in total and central obesity. Among adipocytokines secreted by the adipose tissue adiponectin is the only one that has a protective role in the development of obesity-related disorders, such as type 2 diabetes and cardiovascular disease. This review aims to present a role that adiponectin may play during the progress of menopause in relation to development of menopausal metabolic syndrome. PMID- 27683318 TI - Measures of Diagnostic Accuracy: Basic Definitions. AB - Diagnostic accuracy relates to the ability of a test to discriminate between the target condition and health. This discriminative potential can be quantified by the measures of diagnostic accuracy such as sensitivity and specificity, predictive values, likelihood ratios, the area under the ROC curve, Youden's index and diagnostic odds ratio. Different measures of diagnostic accuracy relate to the different aspects of diagnostic procedure: while some measures are used to assess the discriminative property of the test, others are used to assess its predictive ability. Measures of diagnostic accuracy are not fixed indicators of a test performance, some are very sensitive to the disease prevalence, while others to the spectrum and definition of the disease. Furthermore, measures of diagnostic accuracy are extremely sensitive to the design of the study. Studies not meeting strict methodological standards usually over- or under-estimate the indicators of test performance as well as they limit the applicability of the results of the study. STARD initiative was a very important step toward the improvement the quality of reporting of studies of diagnostic accuracy. STARD statement should be included into the Instructions to authors by scientific journals and authors should be encouraged to use the checklist whenever reporting their studies on diagnostic accuracy. Such efforts could make a substantial difference in the quality of reporting of studies of diagnostic accuracy and serve to provide the best possible evidence to the best for the patient care. This brief review outlines some basic definitions and characteristics of the measures of diagnostic accuracy. PMID- 27683317 TI - Bone Turnover Markers and Osteoprotegerin in Uncomplicated Pregnancy. AB - Although calcium metabolism during pregnancy is well described the mechanisms involved in bone metabolism are not quite clear. Increase of osteoprotegerin (OPG) with elevated bone turnover is supposed to be a homeostatic mechanism limiting bone loss. The aim of the study was to assess bone turnover in pregnancy in relation to serum osteoprotegerin level. Osteocalcin (OC), beta-crosslaps (CTx), OPG, vitamin 25 OH D3, parathormone (PTH), and calcium (Ca) were determined in 30 healthy women at 1(st) and at 3(rd) trimester of pregnancy and 27 healthy age-matched non pregnant women. In pregnant women average OPG, CTx and serum calcium concentrations were found to be highly elevated. During pregnancy OPG and bone resorption significantly rised whereas only slight increase in OC level was found with concomitant decrease in serum calcium. OPG correlated positively with OC and Ca only at 1(st) trimester. Serum CTx and OPG at 1(st) trimester seemed to be the only parameters to differentiate between elevated and normal bone turnover among pregnant women. In pregnancy bone turnover increases mainly due to enhanced bone resorption. The determination of osteocalcin at the beginning of pregnancy seems to be of limited clinical use, whereas measuring bone resorption markers such as CTx and/or osteoprotegerin may have a good predictive value for later pregnancy-associated bone loss. PMID- 27683320 TI - The Eight EFCC Continuous Postgraduate Course in Clinical Chemistry: New Trends in Classification, Diagnosis and Management of Kidney Diseases. PMID- 27683321 TI - 1. Pathophysiology and Classification of Kidney Diseases. PMID- 27683311 TI - The role of hydrogen sulfide in aging and age-related pathologies. AB - When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the 'hallmarks of aging'. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H2S) in the regulation of aging. Nowadays, H2S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H2S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies. PMID- 27683322 TI - 2. Inflammation, Cytokines and Chemokines in Chronic Kidney Disease. PMID- 27683323 TI - 3. Podocyte Injury in Glomerular Diseases. PMID- 27683324 TI - 4. Kidneys and Autoimmune Disease. PMID- 27683325 TI - 5. Hereditary Kidney Disorders. PMID- 27683327 TI - 7. Drug-Induced Kidney Injury. PMID- 27683326 TI - 6. Diabetic Nephropathy. PMID- 27683328 TI - 8. Dyslipidemia at Chronic Renal Failure. PMID- 27683329 TI - 9. GFR - Where are We Now? PMID- 27683330 TI - 10. Cardiovascular Risk in Chronic Kidney Disease. PMID- 27683331 TI - 11. Laboratory Standards in the Diagnosis and Monitoring of Therapy. PMID- 27683332 TI - 12. The Urinary Proteomics: A Tool to Discover New and Potent Biomarkers for Kidney Damage. PMID- 27683333 TI - 13. Point-of-Care Creatinine Testing in High-Risk Patients. PMID- 27683334 TI - 14. Recent Approaches to Therapy: Is There Real Progress? PMID- 27683335 TI - Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application. AB - Iron uptake, utilisation, release and storage occur at the gene level. Individuals with variant forms of genes involved in iron metabolism may have different requirements for iron and are likely to respond differently to the same amount of iron in the diet, a concept termed nutrigenetics. Iron deficiency, iron overload and the anemia of inflammation are the commonest iron-related disorders. While at least four types of hereditary iron overload have been identified to date, our knowledge of the genetic basis and consequences of inherited iron deficiency remain limited. The importance of genetic risk factors in relation to iron overload was highlighted with the identification of the HFE gene in 1996. Deleterious mutations in this gene account for 80-90% of inherited iron overload and are associated with loss of iron homeostasis, alterations in inflammatory responses, oxidative stress and in its most severe form, the disorder hereditary haemochromatosis (HH). Elucidation of the genetic basis of HH has led to rapid clinical benefit through drastic reduction in liver biopsies performed as part of the diagnostic work-up of affected patients. Today, detection of a genetic predisposition in the presence of high serum ferritin and transferrin saturation levels is usually sufficient to diagnose HH, thereby addressing the potential danger of inherited iron overload which starts with the same symptoms as iron deficiency, namely chronic fatigue. This review provides the scientific back-up for application of pathology supported genetic testing, a new test concept that is well placed for optimizing clinical benefit to patients with regard to iron status. PMID- 27683336 TI - Hepcidin and Its Role in Iron Homeostasis. AB - Hepcidin, a small peptide secreted mainly by the liver, plays a central role in iron status regulation. The experiments on hepcidin seemed very promising and gave new life to understanding iron metabolism. Many authors suggest that hepcidin measurement can be used as a clinical tool for the diagnosis and management of a wide range of iron-related disorders. The current review presents data concerning hepcidin, especially its biology, mechanism of action and its role in pathomechanism of many diseases. PMID- 27683337 TI - The Impact of Sex and Age on Serum Prohepcidin Concentration in Healthy Adults. AB - INTRODUCTION: Within the last 8 years, it has become evident that hepcidin has a diagnostic and therapeutic potential. Therefore, it is a great need to establish the reference interval for hepcidin and its precursor. The aim of this study was to assess the impact of age and sex on serum prohepcidin concentration in healthy adults. MATERIAL AND METHODS: 100 healthy volunteers were enrolled during the 18 months of the study - 56 males and 44 females, mean age 34.8+/-10.1 yrs. Serum prohepcidin, ferritin, soluble transferring receptor (sTfR) and plasma erythropoietin were examined by enzyme-linked immunosorbent assay (ELISA) kits. Serum iron and unsaturated iron binding capacity were determined on ARCHITECT ci8200 (Abbott Diagnostics) according to the manufacturer's instructions. RESULTS: Serum prohepcidin concentrations ranged from 74.9 ng/ml to 300.4 ng/ml in healthy adults of both sexes. However, prohepcidin levels were significantly higher in males (median value 145.7 ng/ml) than in females (median 127.3 ng/ml) (p=0.0016). Serum prohepcidin was not associated with age in the group of healthy adults. CONCLUSIONS: Serum prohepcidin concentrations were found to be related to sex. Significantly lower prohepcidin levels were observed in females compared with males. PMID- 27683338 TI - Determination of Serum Ferritin Glycosylation in Hyperferritinemia Associated to Iron Overload and Inflammation. AB - BACKGROUND: Serum ferritin is a commonly used clinical biochemical parameter and hyperferritinemia is used as a surrogate marker for iron overload, acute or chronic inflammation, malignancy or cell death. The aim of the present study was to develop purification strategies of ferritin from sera to determine if micro heterogeneity of serum ferritin can be used to differentiate the underlying cause of the hyperferritinemia. PATIENTS MATERIALS AND METHODS: Sera from patients with hemochromatosis, rheumatologic diseases, aceruloplasminemia, ferroportin disease or iron loading anemia have been collected and stored and ferritin purified by negative affinity followed by ion exchange and size exclusion chromatography. Purified serum ferritin was analyzed by western blotting and MALDI TOF mass spectrometry and the spectra compared with the results from ferritin isolated from human liver, spleen and placenta. RESULTS: By Western blotting a major band of 19kD has been found in most sera, suggesting that the L-ferritin is the predominant isoform present in serum regardless of the cause of hyperferritinemia. Multistep chromatography can be used for significant enrichment and purification of ferritin from serum, which can be further analyzed by MALDI TOF MS. Tryptic digestion and peptide mass finger-printing by MALDI TOF MS of ferritin purified from human tissues shows differential spectra. DISCUSSION AND CONCLUSIONS: Analysis of ferritin micro-heterogeneity by MALDI TOF allows determination of the tissue origin of ferritin, which could be applied in the differential diagnostic workup of hyperferritinemia. PMID- 27683339 TI - Standardization in Clinical Enzymology. AB - The goal of standardization in Laboratory Medicine is to achieve comparable results in human samples, independent of the reagent kits, instruments, and laboratory where the assay is carried out. To pursue this objective in clinical enzymology, the IFCC has established reference measurement systems for the most important clinical enzymes. These systems are based on the following requirements: a) reference methods, well described in procedures that are extensively evaluated; b) suitable reference materials; and c) reference laboratories operating in a highly controlled manner. Using these reference systems and the manufacturer's standing procedures, industry can assign traceable values to commercial calibrators. Clinical laboratories, which use routine procedures with validated calibrators to measure enzymes in human specimens, can finally obtain values which are traceable to higher-order reference procedures. These reference systems constitute the structure of the traceability chain to which the enzyme routine methods can be linked via an appropriate calibration process, provided that they have a comparable specificity (i.e. they are measuring the same quantity). PMID- 27683340 TI - Standardization in Clinical Enzymology - Results of a Survey Performed in 2008 in Big Hospital Laboratories in Poland. AB - The survey was performed in December 2008 in 21 big hospital laboratories in Poland. The purpose of this survey was to estimate how the IFCC standardization in clinical enzymology is recognized and followed in medical laboratories. Each participant received a short questionnaire in an electronic version consisting of 5 questions dealing with the main features for the Reference Procedures for measurement of catalytic activity concentrations of CK, LDH, GGTP, AST and ALT. Measurement temperature for all enzyme assays in question was 37 degrees C and wavelenght was 340 nm for LDH, ALT, AST and CK in all but one lab. Most of laboratories (80%) performed GGTP assay according to the reference procedure. Surprisingly, the methods used for the LDH measurement were discordant with the IFCC reference procedure in respect to reaction principle in 50% of laboratories. On the other hand, methods for measurements of catalytic activity concentration of ALT and AST were incompatible with the IFCC reference procedures in respect to reaction mixture composition in 55% of laboratories. PMID- 27683341 TI - Government stewardship of the for-profit private health sector in Afghanistan. AB - Background: Since 2003, Afghanistan's largely unregulated for-profit private health sector has grown at a rapid pace. In 2008, the Ministry of Public Health (MoPH) launched a long-term stewardship initiative to oversee and regulate private providers and align the sector with national health goals. Aim: We examine the progress the MoPH has made towards more effective stewardship, consider the challenges and assess the early impacts on for-profit performance. Methods: We reviewed publicly available documents, publications and the grey literature to analyse the development, adoption and implementation of strategies, policies and regulations. We carried out a series of key informant/participant interviews, organizational capacity assessments and analyses of hospital standards checklists. Using a literature review of health systems strengthening, we proposed an Afghan-specific definition of six key stewardship functions to assess progress towards MoPH stewardship objectives. Results: The MoPH and its partners have achieved positive results in strengthening its private sector stewardship functions especially in generating actionable intelligence and establishing strategic policy directions, administrative structures and a legal and regulatory framework. Progress has also been made on improving accountability and transparency, building partnerships and applying minimum required standards to private hospitals. Procedural and operational issues still need resolution and the MoPH is establishing mechanisms for resolving them. Conclusions: The MoPH stewardship initiative is notable for its achievements to date under challenging circumstances. Its success is due to the focus on developing a solid policy framework and building institutions and systems aimed at ensuring higher quality private services, and a rational long-term and sustainable role for the private sector. Although the MoPH stewardship initiative is still at an early stage, the evidence suggests that enhanced stewardship functions in the MoPH are leading to a more efficient and effective for-profit private sector. These successful early efforts offer high-leverage potential to rapidly scale up going forward. PMID- 27683343 TI - Molecular Classification of Breast Cancer Tumours from Patients Treated with Doxorubicin and Docetaxel. AB - It is known that four main molecular breast cancer subtypes have different prognoses and different responses to therapy. Luminal A tumours have a better prognosis and they tend to be sensitive to anti-estrogen drugs. Luminal B tumours have incomplete sensitivity to endocrine therapy. Her2 tumours, which have an aggressive natural history, are sensitive to trastuzumab. Finally, basal-like tumours might be eligible for chemotherapy. The aim of this study was to evaluate the chemosensitivity to docetaxel and doxorubicin of breast cancer subtypes. Patients with locally advanced breast cancer were randomized to receive 4 cycles of full dose doxorubicin (75 mg/m2) or docetaxel (100 mg/m2). After the fourth cycle, patients were submitted to surgery to ascertain pathological response. Treatment response was assessed according to Symmans classification. Among 130 samples analysed most ER positive tumours were luminal subtype. 41% of Her2 positive tumours assessed by immunohistochemistry and FISH were Her2 according to the gene expression profile. Luminal A and normal-like tumours have low expression of proliferation genes as well as ki67, whereas Her2 and basal-like tumours are highly proliferative. Both treatments have the same efficiency (20% of responses). However, basal tumours have the poorest outcome in the doxorubicin branch (0% of responses) while they are the most sensitive to docetaxel (50% of responses). Luminal and normal-like tumours have the poorest responses to both treatments. Finally, Her2 tumours had similar outcome in both branches (20% of responses). Genomic classification may assist the physician to choose a specific treatment based on the sub-type of tumour. This study provides the basis for building individualized neoadjuvant therapies for breast cancer. PMID- 27683342 TI - Rational Laboratory Diagnostics of Antiphospholipid Antibodies: Anti-Cardiolipin, Anti-beta2-Glycoprotein I, Anti-Prothrombin and Anti-Annexin V Antibodies. AB - A possible co-appearance of anticardiolipin (aCL), anti-beta2-glycoprotein I (anti-beta2-GPI), anti-prothrombin (aPT) and anti-annexin V (aANXV) antibodies of IgG, IgM and IgA class were studied in 58 patients with SLE alone and 32 patients APS in the view of rational laboratory diagnostics. The presence of anti phospholipid antibodies (aPL) were defined by our in-house ELISA methods. Out of 17 aCL negative SLE patients 6 had other antigenically defined aPL antibodies. In 13 patients only IgA but not IgG and IgM anti-beta2GPI were detected. Different combinations of aPL subsets were equally distributed in APS and SLE groups. The prevalence of aANXV were similar in APS and SLE patients which was not the case with other aPL. Our findings support the idea of measuring additional subsets of aPL (aPT and aANXV) in unclear cases. IgA (either aCL or anti-beta2-GPI) improved neither the diagnostic specificity nor diagnostic sensitivity, but only increased the frequency of the total anti-beta2-GPI. PMID- 27683344 TI - Multiplex Immunoassays: Chips and Beads. AB - Multiplex analysis is intended to simultaneously look for multiple targets in one sample. This approach has been largely adopted in genomics and progressively expands to various domains of laboratory investigation. In protein analysis, immunoassays are the fundamental methods and their multiplexing and miniaturization is of great applicability to both basic and applied research. Furthermore, the potential of these high-throughput methodologies can be foreseen in the field of clinical diagnostics. The following text describes planar and bead-based arrays, two main strategies of immunoassay multiplexing. Principles, detection methods and strengths of each are shortly discussed. Finally, we mention several challenges linked with the integration of these methods to diagnostics. PMID- 27683345 TI - Production of Cystatin C Wild Type and Stabilized Mutants. AB - Cystatin C is produced in all nucleated cells. It has various functions and biological activities. Researchers are focused on its role in kidney diseases as a marker of glomerular filtration but also as a very important link in development of amyloid diseases. This work describes expression and purification of both wild type (wt) and stabilized form (stab 1 and 2) of wt cystatin C and amyloid-forming L68Q mutant of cystatin C. The recombinant cystatin C can be used in projects requiring pure cystatin C to examine models of dimerization and fibrils formation as well as a standard in clinical tests. PMID- 27683346 TI - Dihydrochalcomycin Production and Glycosyltransferase from Streptomyces SP. KCTC 0041BP. AB - The dihydrochalcomycin (GERI) synthetic gene cluster from Streptomyces sp. KCTC 0041BP has been isolated. Two open reading frames (ORFs), designated gerT1 and gerT2 as glycosyltransferase genes, has been identified by sequence analysis. GerT1 encodes for the protein function as dTDP-deoxyallosyltransferase and it is responsible to the attachment of dTDP-allose to the macrolide ring. Similarly, gerT2 encodes for peptide named as dTDP-chacosyltransferase which can transfers the dTDP-4,6-dideoxyglucose to macrolactone core. During process of compound isolation, a new compound has been isolated with molecular weight m/z 755 [M+Na+]. This compound could be the dihydrochalcomycin derivative. The compound has been shown the same antibacterial activity as GERI compound. PMID- 27683347 TI - Challenges of Endocrine Function Testing in Resource Poor Settings. PMID- 27683348 TI - Does sports participation (including level of performance and previous injury) increase risk of osteoarthritis? A systematic review and meta-analysis. AB - BACKGROUND: To assess the relationship between sport and osteoarthritis (OA), and specifically to determine whether previous participation, in terms of level (elite or non-elite), type of sport, intensity or previous injury, was associated with OA. METHODS: This systematic review was developed using PRISMA guidelines. Databases were searched (to May 2016). Narrative review and meta-analysis (with risk ratio (RR) and 95% CIs) approaches were undertaken where appropriate. Study quality was assessed using GRADE. RESULTS: 46 studies were included. Narratively, 31 studies reported an increased risk of OA, with 19 demonstrating an increased risk in elite athletes. There was an increased risk after sports exposure (irrespective of type; RR 1.37; 95% CI 1.14 to 1.64; 21 studies). It remained uncertain whether there was a difference in risk of OA between elite and non elite athletes (RR 1.37; 95% CI 0.84 to 2.22; 17 studies). The risk was higher in soccer (RR 1.42; 95% CI 1.14 to 1.77; 15 studies) but lower in runners (RR 0.86; 95% CI 0.53 to 1.41; 12 studies). 9 studies showed an association with the intensity of sport undertaken and OA. 5 studies demonstrated a higher prevalence of OA following meniscectomies and anterior cruciate ligament tears. Overall, the evidence was of GRADE 'very low' quality. CONCLUSIONS: There was very low-quality evidence to support an increased relationship between sports participation and OA in elite participants. It is unclear whether there is a difference in risk between elite and non-elite participants with further prospective studies needed to evaluate this. Pooled findings suggested that significant injuries were associated with OA in soccer players. PMID- 27683349 TI - National Football League concussion lawsuit: what it means for other sports and observations from Singapore Rugby. PMID- 27683351 TI - The Interaction of Apolipoprotein E and Angiotensin I-Converting Enzyme Dna Polymorphisms with Hypertension on Early Ischemic Stroke Risk. AB - Combinations of multiple predisposing polymorphisms and their interactions with modifiable factors may result in synergistic effects on early ischemic stroke risk. We evaluated the potential interaction of apolipoprotein (apo) E and angiotensin I-converting enzyme (ACE) gene polymorphisms and hypertension on early ischemic stroke risk in Serbian population. We analyzed 65 stroke patients (mean age 35 yrs) and age- and body mass index matched 330 controls. ACE genotypes were determined by polymerase chain method (PCR) and apoE genotypes by PCR appended by HhaI restriction fragment-length polymorphism/MADGE analysis. Odds ratios (ORs) for stroke were 1.35 (95% confidence interval (CI) 0.50-3.62) in subjects with one studied polymorphism and 3.78 (95% CI, 1.28-11.18) in those with two. Compared with nonhypertensive subjects bearing no polymorphisms, ORs were 2.73 (95% CI 0.32-17.55) and 4.80 (95% CI 0.50-28.12) for nonhypertensive subjects with one and two polymorphisms, 8.53 (95% CI 1.04-62.47) and 30.00 (95% CI 3.21-186.45) for hypertensive. These data suggest a gene-dose effect of the examined gene variants and a synergistic effect of these polymorphisms and hypertension in the pathogenesis of early ischemic stroke. PMID- 27683350 TI - Use of Biomarkers in Screening for Cancer. AB - BACKGROUND: Screening for premalignant lesions or early invasive disease has the potential to reduce mortality from cancer. Potential screening tests for malignancy include measurement of (bio)markers. CONTENT: The literature relevant to the use of biomarkers as screening tests for cancer was reviewed with particular attention given to systematic reviews, prospective randomised trials and guidelines published by Expert Panels. Because of their ease of measurement, several biomarkers have been evaluated or are currently undergoing evaluation as screening tests for early malignancy. These include the use of vanillymandelic acid and homovanillic acid in screening for neuroblastoma in newborn infants, AFP in screening for hepatocellular cancer in high-risk subjects, CA 125 in combination with transvaginal ultrasound (TVU) in screening for ovarian cancer, PSA in screening for prostate cancer and fecal occult blood testing (FOBT) in screening for CRC. Of these markers, only the use of FOBT in screening for CRC has been shown to reduce mortality from cancer. Large randomized prospective trials are currently in progress aimed at evaluating the potential value of PSA screening in reducing mortality from prostate cancer and CA 125 in combination with TVU in reducing mortality form ovarian cancer. CONCLUSION: Although biomarkers have many attractions as screening tests, inadequate sensitivity and specificity, when combined with the low prevalence of cancer in asymptomatic subjects, limit their value for the early detection of malignancy. Screening has been defined as the systematic application of a test to identify subjects at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action, among persons who have not sought medical attention on account of symptoms of that disorder (1). To be of value, screening must detect disease earlier and result in an efficacious treatment and the earlier use of efficacious treatment must lead to better outcome compared to treatment available at the onset of symptoms (2). Screening differs from diagnosis in that the aim is to detect disease or a predisease state when subjects are asymptomatic. Currently, only a small number of screening tests have been shown to reduce mortality from cancer. These include mammography in screening for breast cancer (especially in women >50 years of age), the Papanicalaou (PAP) test in screening for cervical cancer and fecal occult blood testing (FOBT) in screening for colorectal cancer (CRC) (for review, see refs. 2,3). Compared to procedures such as radiology, cytology and endoscopy, the use of biomarkers as cancer screening tests have several advantages (4). These advantages include: Biomarkers can be measured in biological fluids such as blood and urine that can be obtained with minimal inconvenience to subjects undergoing screening. This in turn should lead to high compliance rates.For many biomarkers, automated assays are available, thus allowing the processing of large numbers of samples in a relatively short period of time.Tests for biomarkers provide quantitative results with objective endpoints.Assays for biomarkers are relatively cheap.In practice however, lack of sensitivity for early invasive disease or premalignant lesions and lack of specificity for malignancy limit the use of existing biomarkers in screening asymptomatic subjects for early malignancy (4,5). This lack of sensitivity and specificity when combined with the low prevalence of cancers in the general population means that most biomarkers, if used alone, have a low positive predictive value in screening asymptomatic populations. Indeed, it is the low prevalence of cancer in the general population that prohibits most biomarkers from being used alone, in screening for cancer (4,5). Despite these limitations, a number of biomarkers have either undergone or are currently undergoing evaluation as potential cancer screening tests. These markers include the use of vanillymandelic acid (VMA) and homovanillic acid (HVA) in screening for neuroblastoma in newborns, AFP in screening for hepatocellular cancer in high risk subjects, CA 125 in combination with transvaginal ultrasound (TVU) in screening for ovarian cancer, PSA in screening for prostate cancer and fecal occult blood testing (FOBT) in screening for CRC. The aim of this article is to critically review the role of these biomarkers in screening normal-risk asymptomatic subjects for early cancer. Screening subjects with a genetic predisposition to cancer will not be discussed. PMID- 27683352 TI - Antioxidant Effects of Lycopene and Ubiquinol-10 on the Oxidative Stress in Rat Hepatocytes Induced by Tert-Buthyl Hydroperoxide. AB - Free radicals especially reactive oxygen metabolites can damage DNA, protein, enzymes, and membrane lipids. Lipid peroxidation in hepatocyte membrane may be involved in hepatic diseases. Antioxidants may inhibit this reaction. Due to oxidant-antioxidant imbalance, free radicals may cause destructive effects. For several years, scientists tried to find antioxidant compounds. In this study, the effects of lycopene and ubiquinol-10 on the oxidative stress in rat hepatocytes induced by t-buthyl hydroperoxide was determined. First, rat hepatocytes were isolated and then incubated in the presence of tert-buthyl hydroperoxide and the amount of malondialdehyde, as a marker of lipid peroxidation, was determined. Then, this reaction was performed in the presence of various concentrations of each lycopene and ubiquinol-10, and the malondialdehyde level was determined. The results of this study showed that in the presence of various concentrations of lycopene and ubiquinol-10 the levels of lipid peroxidation products significantly decreased (P<0.05). Thus, lycopene and ubiquinol-10 have inhibitory effects on lipid peroxidation reaction. This study showed the potential utility of lycopene and ubiquinol-10 in prevention of hepatic dysfunction. PMID- 27683353 TI - The Study of Hemodialysis Effectiveness on the Change Rate of Lipid Peroxidation and L-Carnitine Level in Hemodialysis Patients. AB - Carnitine is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in beta-oxidation of fatty acids. Carnitine is a scavenger of oxygen free radicals in mammalian tissues. Lack of carnitine in a hemodialysis patient can lead to carnitine deficiency. Oxidation of fatty acids and lipid metabolism are severly affected by carnitine deficiency. Oxidative stress is defined as imbalance between formation of free radicals and antioxidative defense mechanisms. It has been proposed to play a role in many disease states. In hemodialysis patients multiple factors can lead to a a high susceptibility to oxidative stress. The aim of this study was to determine hemodialysis effectiveness on the change rate of serum L-carnitine and lipid peroxidation. 27 patients with chronic renal failure (24-80 yrs) who undergo hemodialysis for 6-12 months were selected (M= 17, F= 10). Malondialdehyde (MDA), as an indicator of lipid peroxidation was measured colorimetrically with a standard thiobarbituric acid (TBA) method. L-carnitine was measured with enzymatic UV method (ROCHE, Spectronic Genesis 2, 340 nm). The weight mean of L carnitine before and after hemodialysis was 7.67+/-3.6 mg/l and 2.07+/-1.6 mg/l, respectively (P<0.001). The weight mean of pre-hemodialysis MDA was 4.17+/-1.24 umol/l, following hemodialysis -4.98+/-1.2 umol/l (P<0.001). Results showed that 55.6% of patients suffered from carnitine defciency. Serum carnitine was found to be decreased markedly after hemodialysis (P<0.001). Our findings indicated that oxidative stress in these patients is further exacerbated by hemodialysis, as evidenced by increased lipid peroxidation. The relationship between serum L carnitine and MDA before and after hemodialysis was observed (r=0.82; p<0.001; r=0.75; p<0.001). PMID- 27683354 TI - Early Origins of Adult Cancer Risk Among Men and Women: Influence of Childhood Misfortune? AB - OBJECTIVE: To examine the effect of five childhood misfortune domains-parental behavior, socioeconomic status, infectious diseases, chronic diseases, and impairments-on all-site and selected site-specific cancer prevalence and all-site cancer incidence. METHOD: Panel data from the Health and Retirement Study (2004 2012) were used to investigate cancer risk among adults above the age of 50. RESULTS: Risky parental behavior and impairment in childhood were associated with higher odds of all-site cancer prevalence, and childhood chronic disease was associated with prostate cancer, even after adjusting for adult health and socioeconomic factors. Moreover, having one infectious disease in childhood lowered the odds of colon cancer. Cancer trends varied by race and ethnicity, most notably, higher prostate cancer prevalence among Black men and lower all site cancer among Hispanic adults. DISCUSSION: These findings underscore the importance of examining multiple domains of misfortune because the type and amount of misfortune influence cancer risk in different ways. PMID- 27683356 TI - About Diode Laser Stapedotomy. PMID- 27683355 TI - Highlights from the Current Issue: October 2016. PMID- 27683357 TI - Laboratory Medicine Specialization Teaching and Training in Italy with a Glance to Some European and Non-European Countries. AB - The Italian Ministry of Education, University and Research has recently reformed the medical schools of specialization in accordance with a series of EC Directives. Four different curricula have been defined into the class of "Diagnostics and Laboratory Medicine", respectively: Anatomic Pathology, Clinical Biochemistry, Clinical Pathology, and Microbiology & Virology. Each curriculum is based on a scheme of 300 credits, that includes formal educational activities) and practical activities distributed on a five years' period. The four curricula share a common course of either formal or practical activities. Main training and professional objectives are in favour of: a) the principles of appropriateness and of evidence based medicine, b) the acquisition of either on-the-bench experience and practice, or skills in organizing and managing the laboratory activities and personnel c) the understanding of data and phenomena relevant to the patients in a clinically oriented vision, d) the ability to translate research results into diagnostic advantages, e) the values of humanism and ethics. When comparing the Italian curriculum with some European and non-European curricula in Laboratory Medicine, many similarities are apparent: above all, the medical pertinence of the profession is increasingly affirmed in favour of a consultancy role to be played by the specialist in Laboratory Medicine at the clinical level. MAIN CONCLUSIONS: a) the education, skill and expertise required for laboratory specialists regard now a broad variety of issues, b) these embrace not only technical, scientific and organizational aspects, but even the ability to develop consultative capacities in different diagnostic areas, c) moreover the implicit translational aspects in the profession require the adoption of innovative and multifaceted curricula. PMID- 27683358 TI - Registration of Medical Laboratory Technologist Qualified Abroad. PMID- 27683359 TI - Current Pre- and Post-Graduate Vocational Education and Training in Laboratory Medicine and Microbiology in Poland. AB - The status of Polish medical laboratories in continuously changing. Since 2001 the legal framework was established for the clinical chemists employed in medical and microbiological laboratories. Since that time, the job performance by clinical chemists is limited only to the specialist, member of the Polish Chamber of Laboratory Diagnosticians. According to that legal act, graduate in laboratory medicine is certified to perform the professional activities in medical or microbiological laboratories without further vocational training. After graduating from biology, chemistry, pharmacy or veterinary medicine, a person can perform the job only under supervision of a certified clinical chemist. Several Medical Universities have organized the system of post-graduation education for such graduates. The main courses taught are basic pathology, internal medicine, hematology, immunology, and clinical chemistry. In addition, the Ministry of Health and Chamber of Laboratory Diagnosticians are organizing and supervising the higher level of post-graduate education for clinical chemists, the education and vocational training which leads to the title of specialist in clinical chemistry or similar area in laboratory medicine. The professional qualification of such person are evaluated during the final exam at the national level. The specialist is eligible to act as director of clinical laboratories. PMID- 27683360 TI - Education in Medical Biochemistry in Serbia. AB - Medical biochemistry is the usual name for clinical biochemistry or clinical chemistry in Serbia. Medical biochemistry laboratories and medical biochemists as a profession are part of Health Care System and are regulated through: the Health Care Law and rules issued by the Chamber of Medical Biochemists of Serbia. The first continuous and organized education for Medical Biochemists in Serbia dates from 1945, when Department of Medical Biochemistry was established at Pharmaceutical Faculty in Belgrade. In 1987 at the same Faculty a five years undergraduate branch was established, educating Medical Biochemists under a special program. Since 2006 the new five year undergraduate (according to Bologna Declaration) and postgraduate program of four-year specialization according to EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine has been established. The Ministry of Education and Ministry of Public Health accredits the programs. There are four requirements for practicing medical biochemistry in the Health Care System: University Diploma of the Faculty of Pharmacy (Medical Biochemistry), successful completion of the profession exam at the Ministry of Health after completion of one additional year of obligatory practical training in medical laboratories, membership in the Serbian Chamber of Medical Biochemists and licence for skilled work issued by Serbian Chamber of Medical Biochemists. PMID- 27683362 TI - Male courtship decisions are influenced by light environment and female receptivity. AB - The appearance of animal colour signals depends jointly upon the ambient light spectrum and the signal's reflectance spectra. Light environment heterogeneity might, therefore, allow individuals to enhance their signal by signalling in an environment that increases signal efficacy. We tested this hypothesis by providing male guppies (Poecilia reticulata), a choice of three light environments in which to display their colour signal to females: green, lilac, and clear. We paired males with both receptive and non-receptive females to test whether female response might affect male behavioural decisions. Males preferred the clear environment in all trials and this environment also resulted in males having the highest average visual contrast. Sexual behaviour was influenced by complex interactions between female receptivity, light environment, and male colour pattern contrast. Males spent significantly more time in the environment in which their colour signal had the highest contrast, but only when paired with receptive females. Significant interactions between light environment and individual male colour components were also seen only in receptive trials. Our results suggest that males use light environment to enhance their colour pattern, but only in the presence of receptive females. PMID- 27683361 TI - Phenotypic innovation through recombination in genome-scale metabolic networks. AB - Recombination is an important source of metabolic innovation, especially in prokaryotes, which have evolved the ability to survive on many different sources of chemical elements and energy. Metabolic systems have a well-understood genotype-phenotype relationship, which permits a quantitative and biochemically principled understanding of how recombination creates novel phenotypes. Here, we investigate the power of recombination to create genome-scale metabolic reaction networks that enable an organism to survive in new chemical environments. To this end, we use flux balance analysis, an experimentally validated computational method that can predict metabolic phenotypes from metabolic genotypes. We show that recombination is much more likely to create novel metabolic abilities than random changes in chemical reactions of a metabolic network. We also find that phenotypic innovation is more likely when recombination occurs between parents that are genetically closely related, phenotypically highly diverse, and viable on few rather than many carbon sources. Survival on a new carbon source preferentially involves reactions that are superessential, that is, essential in many metabolic networks. We validate our observations with data from 61 reconstructed prokaryotic metabolic networks. Our systematic and quantitative analysis of metabolic systems helps understand how recombination creates innovation. PMID- 27683363 TI - Reconstructing the emergence of a lethal infectious disease of wildlife supports a key role for spread through translocations by humans. AB - There have been few reconstructions of wildlife disease emergences, despite their extensive impact on biodiversity and human health. This is in large part attributable to the lack of structured and robust spatio-temporal datasets. We overcame logistical problems of obtaining suitable information by using data from a citizen science project and formulating spatio-temporal models of the spread of a wildlife pathogen (genus Ranavirus, infecting amphibians). We evaluated three main hypotheses for the rapid increase in disease reports in the UK: that outbreaks were being reported more frequently, that climate change had altered the interaction between hosts and a previously widespread pathogen, and that disease was emerging due to spatial spread of a novel pathogen. Our analysis characterized localized spread from nearby ponds, consistent with amphibian dispersal, but also revealed a highly significant trend for elevated rates of additional outbreaks in localities with higher human population density-pointing to human activities in also spreading the virus. Phylogenetic analyses of pathogen genomes support the inference of at least two independent introductions into the UK. Together these results point strongly to humans repeatedly translocating ranaviruses into the UK from other countries and between UK ponds, and therefore suggest potential control measures. PMID- 27683364 TI - An aquatic vertebrate can use amino acids from environmental water. AB - Conventional food-web theory assumes that nutrients from dissolved organic matter are transferred to aquatic vertebrates via long nutrient pathways involving multiple eukaryotic species as intermediary nutrient transporters. Here, using larvae of the salamander Hynobius retardatus as a model system, we provide experimental evidence of a shortcut nutrient pathway by showing that H. retardatus larvae can use dissolved amino acids for their growth without eukaryotic mediation. First, to explore which amino acids can promote larval growth, we kept individual salamander larvae in one of eight different high concentration amino acid solutions, or in control water from which all other eukaryotic organisms had been removed. We thus identified five amino acids (lysine, threonine, serine, phenylalanine, and tyrosine) as having the potential to promote larval growth. Next, using 15N-labelled amino acid solutions, we demonstrated that nitrogen from dissolved amino acids was found in larval tissues. These results suggest that salamander larvae can take up dissolved amino acids from environmental water to use as an energy source or a growth-promoting factor. Thus, aquatic vertebrates as well as aquatic invertebrates may be able to use dissolved organic matter as a nutrient source. PMID- 27683365 TI - A touch of sleep: biophysical model of contact-mediated dormancy of archaea by viruses. AB - The canonical view of the interactions between viruses and their microbial hosts presumes that changes in host and virus fate requires the initiation of infection of a host by a virus. Infection may lead to the death of the host cell and release of viruses, to the elimination of the viral genome through cellular defence mechanisms or the integration of the viral genome with the host as a chromosomal or extrachromosomal element. Here, we revisit this canonical view, inspired by recent experimental findings in which the majority of target host cells can be induced into a dormant state when exposed to either active or deactivated viruses, even when viruses are present at low relative titre. We propose that both the qualitative phenomena and the quantitative timescales of dormancy induction are consistent with the hypothesis that cellular physiology can be altered by contact on the surface of host cells rather than strictly by infection In order to test this hypothesis, we develop and study a biophysical model of contact-mediated dynamics involving virus particles and target cells. We show how virus particles can catalyse cellular transformations among many cells, even if they ultimately infect only one (or none). We also find that population scale dormancy is robust to variation in the representation of model dynamics, including cell growth, death and recovery. PMID- 27683366 TI - Evolution of transgenerational immunity in invertebrates. AB - Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host-parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produce both philopatric and dispersing individuals, it may pay to have a plastic allocation strategy with a higher transgenerational immunity investment in philopatric offspring because they are more likely to encounter locally adapted pathogens. We review all experimental studies published to date, comprising 21 invertebrate species in nine different orders, and we show that, as expected, longevity and dispersal correlate with the transfer of immunity to offspring. The validity of our prediction regarding the plasticity of investment in transgenerational immunity remains to be tested in invertebrates, but also in vertebrate species. We discuss the implications of our work for the study of the evolution of immunity, and we suggest further avenues of research to expand our knowledge of the impact of transgenerational immune protection in host-parasite interactions. PMID- 27683367 TI - One fly to rule them all-muscid flies are the key pollinators in the Arctic. AB - Global change is causing drastic changes in the pollinator communities of the Arctic. While arctic flowers are visited by a wide range of insects, flies in family Muscidae have been proposed as a pollinator group of particular importance. To understand the functional outcome of current changes in pollinator community composition, we examined the role of muscids in the pollination of a key plant species, the mountain avens (Dryas). We monitored the seed set of Dryas across 15 sites at Zackenberg, northeast Greenland, and used sticky flower mimics and DNA barcoding to describe the flower-visiting community at each site. To evaluate the consequences of shifts in pollinator phenology under climate change, we compared the flower visitors between the early and the late season. Our approach revealed a diverse community of insects visiting Dryas, including two thirds of all insect species known from the area. Even against this diverse background, the abundance of muscid flies emerged as a key predictor for seed set in Dryas, whereas overall insect abundance and species richness had little or no effect. With muscid flies as the main drivers of the pollinating function in the High Arctic, a recently observed decline in their abundances offers cause for concern. PMID- 27683369 TI - Convergent evolution of ramified antennae in insect lineages from the Early Cretaceous of Northeastern China. AB - Antennae are important, insect sensory organs that are used principally for communication with other insects and the detection of environmental cues. Some insects independently evolved ramified (branched) antennae, which house several types of sensilla for motion detection, sensing olfactory and chemical cues, and determining humidity and temperature levels. Though ramified antennae are common in living insects, occasionally they are present in the Mesozoic fossil record. Here, we present the first caddisflies with ramified antennae, the earliest known fossil sawfly, and a scorpionfly also with ramified antennae from the mid-Lower Cretaceous Yixian Formation of Northeastern China, dated at 125 million years ago (Ma). These three insect taxa with ramified antennae consist of three unrelated lineages and provide evidence for broad structural convergence that historically has been best demonstrated by features such as convergent mouthparts. In addition, ramified antennae in these Mid-Mesozoic lineages likely do not constitute a key innovation, as they are not associated with significantly increased diversification compared with closely related lineages lacking this trait, and nor are they ecologically isolated from numerous, co-occurring insect species with unmodified antennae. PMID- 27683368 TI - Hybridization as a facilitator of species range expansion. AB - Explaining the evolution of species geographical ranges is fundamental to understanding how biodiversity is distributed and maintained. The solution to this classic problem in ecology and evolution remains elusive: we still do not fully know how species geographical ranges evolve and what factors fuel range expansions. Resolving this problem is now more crucial than ever with increasing biodiversity loss, global change and movement of species by humans. Here, we describe and evaluate the hypothesis that hybridization between species can contribute to species range expansion. We discuss how such a process can occur and the empirical data that are needed to test this hypothesis. We also examine how species can expand into new environments via hybridization with a resident species, and yet remain distinct species. Generally, hybridization may play an underappreciated role in influencing the evolution of species ranges. Whether-and to what extent-hybridization has such an effect requires further study across more diverse taxa. PMID- 27683370 TI - Host coevolution alters the adaptive landscape of a virus. AB - The origin of new and complex structures and functions is fundamental for shaping the diversity of life. Such key innovations are rare because they require multiple interacting changes. We sought to understand how the adaptive landscape led to an innovation whereby bacteriophage lambda evolved the new ability to exploit a receptor, OmpF, on Escherichia coli cells. Previous work showed that this ability evolved repeatedly, despite requiring four mutations in one virus gene. Here, we examine how this innovation evolved by studying six intermediate genotypes of lambda isolated during independent transitions to exploit OmpF and comparing them to their ancestor. All six intermediates showed large increases in their adsorption rates on the ancestral host. Improvements in adsorption were offset, in large part, by the evolution of host resistance, which occurred by reduced expression of LamB, the usual receptor for lambda. As a consequence of host coevolution, the adaptive landscape of the virus changed such that selection favouring four of the six virus intermediates became stronger after the host evolved resistance, thereby accelerating virus populations along the path to using the new OmpF receptor. This dependency of viral fitness on host genotype thus shows an important role for coevolution in the origin of the new viral function. PMID- 27683371 TI - Evolution of a butterfly dispersal syndrome. AB - The existence of dispersal syndromes contrasting disperser from resident phenotypes within populations has been intensively documented across taxa. However, how such suites of phenotypic traits emerge and are maintained is largely unknown, although deciphering the processes shaping the evolution of dispersal phenotypes is a key in ecology and evolution. In this study, we created artificial populations of a butterfly, in which we controlled for individual phenotypes and measured experimentally the roles of selection and genetic constraints on the correlations between dispersal-related traits: flight performance and wing morphology. We demonstrate that (i) trait covariations are not due to genetic correlations, (ii) the effects of selection are sex-specific, and (iii) both divergent and stabilizing selection maintain specific flight performance phenotypes and wing morphologies. Interestingly, some trait combinations are also favoured, depending on sex and fitness components. Moreover, we provide evidence for the role of (dis)assortative mating in the evolution of these dispersal-related traits. Our results suggest that dispersal syndromes may have high evolutionary potential, but also that they may be easily disrupted under particular environmental conditions. PMID- 27683373 TI - Laboratory Medicine as a Profession and Clinical Science - How to Perform Both of them well? PMID- 27683372 TI - Maternal stress has divergent effects on gene expression patterns in the brains of male and female threespine stickleback. AB - Maternal stress can have long-term effects on neurodevelopment that can influence offspring performance and population evolutionary trajectories. To examine the mechanistic basis for these neurodevelopmental effects of maternal stress, we used RNA-seq to assess differential gene expression across the brain transcriptome of adult male and female threespine stickleback (Gasterosteus aculeatus) from stressed and unstressed mothers. We identified sexually divergent effects of maternal stress on the brain transcriptome. In males, genes that were upregulated by maternal stress were enriched for processes involved in synaptic function and organization and steroid hormone-mediated signalling pathways, whereas in females genes that were upregulated by maternal stress were enriched for processes involved in protein translation and metabolic functions. The expression of several genes involved in the hypothalamic-pituitary-interrenal response to stress and epigenetic processes such as the regulation of DNA methylation patterns and miRNAs increased in males and not in females. These data suggest that maternal stress has markedly different effects on cellular pathways in the brains of male and female offspring of mothers that are exposed to stress, which could have important implications when assessing the long-term ecological and evolutionary impacts of stress across generations. PMID- 27683374 TI - Laboratory Medicine in the Scope of Proteomics and Genomics. AB - Advances in technology, especially in molecular biology, allow for a fast expansion of diagnostic methods in routine clinical practice. New proteomics and genomics technologies could be used for disease specific biomarker discovery and to monitor patient response to the therapy. Genomics and proteomics may also help to establish new, molecular classification of the disease. Applying genomic and proteomic methods to body fluids (serum, cerebrospinal fluid, urine, etc) and tissue extracts would place valuable objective analytical power in the hands of the clinician however validation of those methods is an important issue. The rapid expansion of the diagnostic tools based on developments in proteomic and genomic technologies can be fundamental for the development of personalized medicine. PMID- 27683375 TI - Non-HDL Cholesterol and Evaluation of Cardiovascular Disease Risk. AB - Cardiovascular disease (CVD), such as coronary heart disease (CHD), is the most frequent cause of death worldwide, especially in developed countries. The latest recommendations of European and American Cardiological Associations emphasize the role of non-HDL cholesterol (non-HDL-C) in evaluating the risk of CVD. Although this parameter has a lot of advantages, it is rarely used by general practitioners in lipid profile assessment. The aim of this article is to present the recent informations on the usage of non-HDL-C in the primary prevention of cardiovascular disease and to compare its diagnostic value to traditional and new CVD risk factors. PMID- 27683376 TI - Serum Adiponectin and Indices of Cardiovascular Risk in Young Women with Excessive Body Mass. AB - Adiponectin reduces oxidative stress, the release of C-reactive protein and influences on the process of atherogenesis reducing lipid accumulation in the blood vessels. The findings on the association of adiponectin with cardiovascular risk are contradictory. This study aimed to assess the relationship between adiponectin and indices of cardiovascular risk in women with excessive body mass. Adiponectin, hsCRP and lipids were measured in blood samples obtained from normoglycemic women with excessive body mass (n=52;BMI>=25 kg/m(2)) aged 25-40 yrs and age-matched healthy controls (n=36; BMI<25kg/m(2)). All subjects underwent blood pressure examination and anthropometric measurements. Median concentration of adiponectin in the serum in women with excessive body mass was significantly lower than in women with normal weight (10,8 vs 15,5 ug/ml; p<0,01). Similarly, median serum concentration of triglycerides, hsCRP and blood pressure values were significantly higher and HDL-cholesterol significantly lower in women with BMI>=25 kg/m(2) in comparison to these with normal BMI, however only HDL-C and hsCRP were found to be beyond widely accepted cut-offs. Hypoadiponectinemia in women with excessive body mass (adiponectin concentration below the 5(th) percentile in the control group) was associated predominantly with abnormally increased median values of hsCRP and blood pressure. Concentrations of total cholesterol, non-HDL-C and LDL-C were also significantly higher in women with excessive body mass and hypoadiponectinemia, however still within the reference range. Our results suggest that adiponectin may be used as a prognostic marker of cardiovascular risk in women with excessive body mass. PMID- 27683377 TI - Letter to the Editor: Unlikeliness Limits Estimation. PMID- 27683379 TI - Comparison of Apolipoprotein Concentrations and Values of APOB:APOAI with Traditional Lipid Measures in Women Diagnosed with Acute Cornonary Syndromes - A Preliminary Report. AB - BACKGROUND: Acute coronary syndromes (ACS) are the leading cause of hospitalization and death in the modern world. Reliable indicators of risk assessment could be useful in clinical investigation. Results from recent studies suggest that apolipoprotein measurement and apoB:apoI ratio are superior to traditional lipids in the estimation of coronary risk. We compared apolipoprotein concentrations and apoB:apoAI index with traditional lipid measures in ACS patients. METHODS: A study group consisted of 94 women diagnosed with ACS (STEMI=21, NSTEMI=25 and UA=48). Clinically healthy volunteers (n=30) served as controls. Measurements of serum cardiac TnI, lipid profile, high sensitivity C reactive protein, apolipoprotein AI and apoB100 concentrations were performed and apoB:apoAI ratio was calculated. RESULTS: ACS patients had significantly decreased median HDL-cholesterol, increased atherogenic indexes TC:HDL-C, apoB:apoAI and abnormally high CRP compared to controls. Median LDL-cholesterol and apoAI concentrations, although significantly higher in ACS patients, remained within the normal range. Comparison of atherogenic indexes in ACS patients has shown increased TC:HDL-C (>4) and apoB:apoAI (>0,3) in 60,4% and 96,8% of which 55,4% had moderate and high risk (>0,6). ApoB:apoAI ratio was of good diagnostic utility for discrimination between ACS cases and non-ACS controls (AUC=0,715), and little better than TC:HDL-C. In both groups similar percentage of increased LDL-C and triglycerides was observed whereas increased apoB concentration was three times more likely in ACS cases. The highest apoB:apoAI was observed predominantly in STEMI cases (49%) whereas the lowest in UA and NSTEMI (30%). CONCLUSIONS: Determination of apolipoproteins and assessment of apoB:apoAI ratio seems to be useful and better tool than traditional lipid measures in assessing risk of acute coronary syndromes in women. PMID- 27683378 TI - Thrombomodulatory Effect of Anti-B2-Glycoprotein I Antibodies on Crystalline Annexin A5 on Phospholipid Bilayers, as Observed by Atomic Force Microscopy. AB - Antibodies against beta2-glycoprotein I are a subset of very heterogeneous family of antiphospholipid antibodies. It is well recognised that anti-beta2 glycoprotein I antibodies are the main pathogenic players in the autoimmune disease known as antiphospholipid syndrome. Many mechanisms have been proposed through which these autoantibodies could cause microplacental, arterial or venous thrombosis. One of the suggested mechanisms is an antiphospholipid antibody mediated disruption of annexin A5 protective crystalline shield on negatively charged phospholipid membranes. In current report the study of beta2-glycoprotein I, anti-beta2-glycoprotein I antibodies and annexin A5 interactions was performed on in vitro model of planar solid-supported phospholipid bilayers and visualized by atomic force microscopy. Planar phospholipid bilayers comprised 30 % L-alpha phosphatidylserine and 70 % L-alpha-phosphatidylcholine. For the study of interactions 10 mg/l annexin A5, 0.15 g/l beta2-glycoprotein I, 10 g/l of IgG fraction from healthy blood donor, 10 g/l of IgG fraction from a patient with anti-beta2-glycoprotein I antibodies and 0.4 g/l of isolated IgG anti-beta2 glycoprotein I antibodies from the same patients in Hepes buffered saline with 1.5 mM Ca2+ were used. We confirmed the clustering of beta2-glycoprotein I on planar phospholipid bilayers. We also found that in the presence of annexin A5, beta2-glycoprotein I does not bind to planar phospholipid bilayers. However, when adding the anti-beta2-glycoprotein I antibodies, the growth of beta2-glycoprotein I-anti-beta2-glycoprotein I antibodies complexes in the presence of incompletely crystallized annexin A5 on planar phospholipid bilayers was observed. Results confirm the possible thrombomodulatory activity of anti-beta2-glycoprotein antibodies through their effect on crystalline annexin A5. In addition, the hypothesis that the presence of possibly pathologic antigen-antibody pair itself is not sufficient to start the pathological process is confirmed and visualized for the first time. PMID- 27683380 TI - Occurrence of Vitamin 25(OH)D3 Insufficiency in Young Women with Metabolic Syndrome. AB - Vitamin D insufficiency is prevalent and may be associated with higher risk for metabolic syndrome. Low serum 25-hydroxyvitamin D3 is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in the pathogenesis of obesity and type 2 diabetes. This study examined the vitamin 25(OH)D3 concentration and its relationship with the metabolic syndrome among 52 young women aged 20-40 yrs with overweight and obese. As defined by revised International Diabetes Federation (IDF 2005) criteria, 27 of the 52 women had the metabolic syndrome (52%). Women with MS had significantly lower mean concentration of vitamin 25(OH)D3. Vitamin D insufficiency was more prevalent in women with MS, compared with those who did not fulfill the criteria for this syndrome (63% vs 37%, respectively) as well as among women with metabolic syndrome mild deficiency occurred much more frequently than in without MS (58% vs 26%, respectively). When serum concentrations of 25(OH)D3 were categorized in tertiles, there was a decreasing prevalence of MS in women with increasing concentrations of 25(OH)D3. The study findings suggest that insufficiency of vitamin 25(OH)D3 is more common in women with excessive body weight and metabolic syndrome than in women with excessive body weight without metabolic syndrome. PMID- 27683382 TI - Trace Technology for Assays of Novel Biomarkers. AB - The availability of an easily measurable specific marker for diagnosis of a disease is an important but not always reachable objective. Emergency area is an area where decisions must be taken as quick as possible, and sometimes it is not clear if the patient is well enough to be treated as an outpatient or must be hospitalized. During last few years many new biomarkers and techniques for their measurement have been developed, and surely some others will appear. The aim of this report was to present TRACE technology for specific assays such as: copeptin, proadrenomedullin and proatrial natriuretic peptide. Ongoing research is being done to decide in which diseases they might be useful and if they will be needed for diagnosis, prognosis or treatment monitoring. Results are not conclusive yet, but in the future some of these markers could be used in routine laboratory work if their utility is documented by new data. PMID- 27683383 TI - Call for Enrolling More Professionals in the IFCC Project on Laboratory Errors and Patient Safety. AB - Patient safety is the foundation of good care. In the last decades, a body of evidence has been accumulated to demonstrate that pre- and post-analytical phase are more vulnerable to errors in laboratory medicine than the analytical phase. Aims of the project of the IFCC Working Group on "Laboratory Errors and Patient Safety" (WG-LEPS) are: a) to develop a series of Quality Indicators (QIs), specifically designed for clinical laboratories, b) to create a common reporting system for clinical laboratories based on standardized data collection, and c) to define state-of the-art and Quality Specifications (QSs) for each QI Preliminary results demonstrate that a Model of Quality Indicators can serve as a tool to monitor and control the pre-, intra- and post-analytical activities. However, only after enrolling a more consistent number of clinical laboratories, it should be possible to assure consistency to the data collected and reliability to the QIs identified and to related QSs. PMID- 27683381 TI - Angiotensin I - Converting Enzyme Gene Polymorphism and Activity in Patients with Ischemic Stroke. AB - The possible association of ACE polymorphism with ischemic stroke (IS) was evaluated in 65 patients with IS and 330 age and BMI-matched controls. ACE genotypes were determined by polymerase chain reaction (PCR). There was no significant difference in ACE genotype/allele frequencies between case and control group (p>0.05). Patients with D allele had 4,7 times higher risk for large vessel IS than healthy persons D allele possessors. Persons with D allele had 9.2 times higher risk for large vessel disease than small vessel disease. These data suggest a possible association of ACE gene polymorphism with pathogenesis of large vessel IS. PMID- 27683384 TI - The Cardiac Markers and Oxidative Stress Parameters in Advanced Non-Small Cell Lung Cancer Patients Receiving Cisplatin-Based Chemotherapy. AB - INTRODUCTION: Cardiotoxicity is a well known long-term consequence of lung cancer chemotherapy, however little is known about early subclinical changes in cardiac function. AIM: The goal of the study was to assess early cardiotoxic effects of cisplatin-containing chemotherapy in stage III and IV lung cancer patients, measuring serum levels of selected cardiac markers in relation to oxidant effects. METHODS: We quantified the immediate impact of chemotherapy on cardiac troponin T (TnT), creatine kinase-myocardial band (CK-MB) and N- terminal pro brain natriuretic peptide (NT-proBNP) in blood samples obtained from 12 non-small cell lung cancer (NSCLC) patients. All markers were measured using commercially available immunoassays. To investigate the oxidant effects of cisplatin containing chemotherapy, we evaluated reduced glutathione (GSH), nitrite (NO2), derivatives of reactive oxygen metabolites (d-ROMs) and thiols (SH). Samples were collected prior to chemotherapy and 1 day after the first cycle of cisplatin administration. RESULTS: Chemotherapy did not cause statistically significant elevations in serum CK-MB. Serum TnT levels were undetectable at both time points in 11 out of 12 patients with a threshold of 0.01 ng/ml. In the single patient with undetectable TnT at the baseline, after the first infusion TnT level reversibly rose to 0.03 ng/ml. The pre-treatment value of NT-proBNP was slightly elevated in 7 out of 12 lung cancer patients. In 1 case NT-proBNP level significantly increased after chemotherapy (from 221.8 to 1489.0 pg/ml p<0.001), in the remaining 11 patients it was stable Cisplatin-based combination chemotherapy induced significant nitrite production in 5 patients (p<0.05). The other measured oxidative stress parameters remained unchanged after the first infusion. CONCLUSION: This pilot study demonstrated occasional elevations of cardiac biomarkers during cisplatin administration. Administration of cisplatin containing chemotherapy caused significant nitroxidative stress in some patients. The relevance of cardiovascular complications in cancer patients and identification individual risk factors of developing cardiovascular toxicity merit further evaluation. PMID- 27683385 TI - Gender Associated Lipid and Apolipoprotein Profile in Patients with Age-Related Macular Degeneration. AB - The role of lipid parameters disorder in the development of age-related macular degeneration (AMD) is unclear. The aim of this study was to analyze lipid profile in these patients and to test the influence of gender on lipid profile of AMD patients, especially in the early and late form of the disease. 82 patients with AMD (mean age 70.3 yrs) and 80 age-matched control subjects were included in this study. Serum lipid and apolipoproteiin levels were determined using standardized methods. AMD patients had significantly higher values of total cholesterol (P=0.000), HDL-cholesterol (P=0.0003) and LDL-cholesterol (P=0.000) compared to control group. Significantly higher values of apo A1 (P=0.039), apo E (P=0.002), total-cholesterol (P=0.000), LDL-chol. (P=0.026), total HDL-chol (P=0.000), HDL3 chol. (P=0.005) and non-HDL-cholesterol (P=0.029) were found in female AMD patients compared to males with AMD. Females with the advanced form of the disease had significantly higher total cholesterol (P=0.006), HDL-C (P=0.004), non HDL-C (P=0.05) and apo E (P=0.014) compared to males with the same form of the disease. There is a significant disorder of lipid parameters in AMD patients especially in females. More severe forms of AMD are followed by the increase of atherogenic lipoproteins and apolipoproteins, and females have higher values of these parameters compared to males with the same form of AMD. PMID- 27683386 TI - Procalcitonin and Other Biomarkers of Sepsis in Newborns in the Intensive Care Unit. AB - Neonatal sepsis is one of the most significant causes of mortality and morbidity in infants. Among numerous parameters available to confirm the presence of sepsis in newborns procalcitonin (PCT) has been chosen. The aim of this study was the determination of PCT, C-reactive protein (CRP) serum amyloid A (SAA), plasminogen, protein C, antithrombin III (AT III) and white blood cell count (WBC) in blood sample obtained by puncture of the umbilical vein. Sixty two newborn infants were included in the study: 31 with suspected bacterial infection and 31 healthy babies Serum procalcitonin was measured using Kryptor analyzer (Brahms Aktiengesellschaft, Germany); serum hsCRP and SAA on the Behring Nephelometer II (Dade Behring Diagnostics GmbH, Marburg, Germany); plasma plasminogen, protein C and AT III on BCT Coagulation system, (Dade Behring Diagnostics GmbH, Marburg, Germany); and WBC count was determined in the whole blood using hematological analyzer ADVIA 120 Hematology System (Bayer, Germany). The obtained mean values of PCT, hsCRP, SAA, WBC, plasminogen, AT III, protein C in newborn's samples with suspected bacterial infection/healthy newborns were: 0.188 ng/L / 0.121 ng/L; 1.20 mg/L / 1.30 mg/L, 1.28% / 1.70%; 16.0 x 10(9)/L/12.0 x 10(9) / L, 61.0% / 59.0%, 52.0% / 64.5%, 39.0% / 41.0%, respectively. Neonates with bacterial infection had significantly higher values of PCT (p <0.001), WBC (p <0.001) and CRP (p <0.05) compared to healthy babies. Based on these results, it may be concluded that procalcitonin is useful for early diagnosis of sepsis in newborns. PMID- 27683387 TI - Vitamin D - Analyte of the Millennium. PMID- 27683388 TI - Why are Chlamydia and HPV Major Public Health Problems? PMID- 27683389 TI - Association Between Vitamin D Deficiency and Allergic Diseases. AB - Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor. PMID- 27683391 TI - Letter to the Editor: Measured Values Incompatible with Human Life. PMID- 27683390 TI - Effect of Oxidative Stress in Hemodialysed Patients. AB - AIMS SUBJECTS AND METHODS: Markers of oxidative stress and inflammatory activation of endothelium, as well as the adipose tissue secreted adipokines, e.g. adiponectin show altered pattern in renal failure. However, their internal relations have not been fully evaluated in this special patient population. In our cross sectional study, beside the routine clinical and biochemical parameters, plasma malondialdehyde, glutathione (GSH), catalase, total peroxidase, as well as serum E-selectin and adiponectin were measured in 70 hemodialysed (HD) patients. RESULTS: GSH showed negative correlations with systolic and diastolic blood pressure (BP) values, while a positive one with HDL cholesterol level, as expected. Interestingly, the level of sE-selectin was inversely correlated only with the age. In multiple regression analyses where anthropometric, BP and laboratory parameters were included and sE-selectin was the dependent variable, the inverse association between the age and level of sE Selectin turned out being an independent factor. CONCLUSIONS: In HD kidney failure patients of the biochemical cardiovascular risk markers those related to oxidative stress, endothelial dysfunction, or altered adipokine homeostasis are not necessarily strongly associated. Larger studies may be needed to confirm our novel observation, a negative and independent correlation of age to sE-Selectin level. PMID- 27683392 TI - Pediatric Intestinal Failure-Associated Liver Disease: Challenges in Identifying Clinically Relevant Biomarkers. AB - BACKGROUND: Intestinal failure-associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug-induced liver injury (DILI), those diagnostic criteria could potentially be used in this population. Using a preexisting database of children treated for IFALD, our aim was to determine if a similar composite biomarker could be applied to this population. STUDY DESIGN: Adult DILI criteria were applied at baseline, when treatment for IFALD (ie, direct bilirubin >=2.0 mg/dL) was initiated. RESULTS: A total of 214 patients with IFALD treated at Boston Children's Hospital were identified; 168 patients were eligible for analysis. Most patients analyzed were male (61%) and preterm (87%). Alkaline phosphatase (ALP) >=2* upper limit of normal (ULN) captured the least amount of DILI (11%), while gamma glutamyltransferase (GGT) >=1* ULN accounted for the most (62%). Using adult DILI criteria, 60 (39%) patients with IFALD were found to have DILI. Substituting GGT >=1* ULN for ALP >=2* ULN improved the sensitivity, with 105 (69%) of patients meeting at least 1 criterion for DILI. CONCLUSION: Numerous challenges made it difficult to apply the DILI criteria to children with IFALD. Direct bilirubin, fractionated ALP, and perhaps GGT may be more suitable. Given its complex etiology and the age-based differences due to hepatic immaturity and growth, a more suitable composite marker needs to be developed to assess IFALD in this population. PMID- 27683393 TI - Vitamin D Status: Current Opinion on Critical Levels for Plasma Calcium and Bone Mineral Homeostasis. AB - Currently there is an unprecedented level of interest regarding the purported wide-ranging beneficial effects of an adequate vitamin D status translating into marked increases in test requests for clinical laboratories. The well characterised endocrine pathway of vitamin D metabolism and action is solely responsible for vitamin D regulating plasma calcium and phosphate homeostasis. A large body of data confirm that vitamin D exerts activities within each of the major bone cells and that these same cells are capable of synthesising the active metabolite, 1,25-dihydroxyvitamin D from 25-hydroxyvitamin D. Such data arising from in vitro studies, animal models and clinical sources are consistent with a paradigm that local metabolism of vitamin D by bone cells to form 1,25 dihydroxyvitamin D and its consequent local actions within bone cells exerts an anabolic effect to increase bone mineral status. The data reviewed here provide plausible mechanisms for both catabolic and anabolic actions of vitamin D on bone depending on dietary calcium intake. PMID- 27683394 TI - The Reference Level of Serum S-100B Protein for Poor Prognosis in Patients with Intracranial Extracerebral Hematoma. AB - BACKGROUND: S-100B protein, blood-brain barrier permeability marker, is one of a few biochemical indicators useful in the evaluation of traumatic brain injury. Our aim was to correlate serum concentration of S-100B with clinical condition and CT head scan findings as well as to estimate the level of the protein significant for clinical outcome prediction. METHODS: The cohort of 41 subjects underwent clinical examination by the neurosurgeon, consciousness was evaluated with Glasgow Coma Scale (GCS). Diagnosis was established on the basis of CT head scans. Venous blood samples were collected before surgery. Serum concentration of S-100B protein was estimated using electrochemiluminesce immunoassays (ECLIA) on Cobas 6000 Analyzer (Roche Diagnostics). Clinical outcome was measured applying Glasgow Outcome Scale (GOS). Finally, data were analyzed with Statistica, v. 8.0 (StatSoft, Inc. 2007). RESULTS: The average S-100B concentration was 0.95 +/- 1.75 MUg/L. Statistical analysis revealed significant correlation between S-100B and GCS, GOS and dimers-D concentration (p<0.001, Spearman correlation test). There were statistically significant differences in the S-100B concentration depending on the presence of brain oedema (1.29+/-2.02 vs. 0.06+/-0.03; p<0.01, Mann-Whitney test) or contusion foci (1.37+/-1.77 vs. 0.72+/-1.92; p<0.01) in CT scans. The S-100B concentration of 0.288 MUg/L was determined as a cut-off point for unfavorable clinical outcome prediction (ROC, p<0.001). CONCLUSIONS: Association between serum S-100B concentration and clinical, radiological or laboratory findings prove its usefulness as a diagnostic marker for assessment of brain trauma severity. The concentration of the protein >0.288 MUg/L is associated with poor prognosis. PMID- 27683395 TI - The Role of IL-33 in the Inflammation Process of Asthma and Atherosclerosis. AB - Interleukin-33 (IL-33) is a newly found cytokine of the interleukin-1 (IL-1) family. It's mainly expressed by epithelial and endothelial cells. This expression is upregulated by pro-inflammatory stimulation, thus has an important role in inflammatory responses, such as hypersensitive diseases (asthma), autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (heart failure) and neurodegenerative diseases (Alzheimer). Several studies explored the complicated mechanism of IL-33 action in asthma and atherosclerosis, as this IL is significantly increased in these pathologies, and suggested its potential use in the therapeutic procedures. PMID- 27683396 TI - Shell We Date? ESR Dating Sangamon Interglacial Episode Deposits at Hopwood Farm, IL. AB - During the Sangamon Episode, North America occasionally experienced warm climates. At Hopwood Farm, IL, a small kettle lake filled with sediment after the Illinois Episode glaciers retreated from southern Illinois. To date those deposits, 14 mollusc samples newly collected with associated sediment from three depths at Hopwood Farm were dated by standard electron spin resonance (ESR) dating. ESR can date molluscs from ~0.5 ka to >2 Ma in age with 5-10% precision, by comparing the accumulated radiation dose with the total radiation dose rate from the mollusc and its environment. Because all molluscs contained <=0.6 ppm U, their ages do not depend on the assumed U uptake model. Using five different species, ESR analyses for 14 mollusc subsamples from Hopwood Farm showed that Unit 3, a layer rich in lacustrine molluscs, dates at 102 +/- 7 ka to 90 +/- 6 ka, which correlates with Marine (Oxygen) Isotope Stage 5c-b. Thus, the period with the highest non-arboreal pollen at Hopwood also correlates with the European Brorup, Dansgaard-Oeschger Event DO 23, a time period when climates were cooling and drying somewhat over the same period. PMID- 27683398 TI - Pentraxin 3 as a Novel Marker in Cardiovascular Diseases? AB - Pentraxin 3 (also known as TNFAIP5, TSG-14) belongs to the superfamily of proteins characterized by cyclic multimeric structure. Pentraxin 3 (PTX3) is synthesized locally at the inflammatory sites by endothelial and smooth muscle cells upon exposure to inflammatory signals such as IL-1beta, TNF-alpha or ox LDL, but not IL-6. Furthermore, PTX3 is highly expressed in vascular cells and myocardial cells in patients with cardiomyopathy. These data suggest that pentraxin 3 may be a useful biomarker for local vascular inflammation and cardiovascular system disorders. PMID- 27683399 TI - Prevalence of Helicobacter Pylori in Different Surgical Diseases: A Preliminary Report. AB - The aim of this study was to explore the prevalence of Helicobacter pylori infection in different surgical diseases in patients with six different cancer types. We analyzed sixty consecutive patients with malignancy (gastric cancer, pancreatic cancer, hepatocellular cancer, intestinal cancer, colon cancer, rectal cancer). Detection of specific IgA and IgG antibodies to Helicobacter pylori in human serum was determined by Enzygnost Anti-Helicobacter pylori II/IgA (IgG) using ELISA processor (Siemens, Germany). This study confirmed statistically significant association between Helicobacter pylori seropositivity and all types of cancer included in the study. All patients had elevated levels of Helicobacter pylori IgA and IgG antibodies. Patients with examined cancer types that underwent abdominal surgery exibited a strong antibody reaction to Helicobacter pylori. PMID- 27683397 TI - Nanoparticles: Is Toxicity a Concern? AB - Nanotechnology involving manipulation of atoms and molecules at the nanoscale is one of the frontier areas of research in modern science. During the last few years, nanotechnology has witnessed breakthroughs in the fields of medicine, environment, therapeutics, drug development and biotechnology. This is due to the unique properties of nanomaterials (e.g. chemical, mechanical, optical, magnetic, and biological) which make them desirable for commercial and medical applications. Considering the theory and practice of using nanoparticles, nanotechnology has a great potential in improving treatment of various disorders and in vitro diagnostics. However, there is not much information available on the toxicity of nanoparticles in relation to human health. Toxic effect of nanomaterials on humans is the primary concern of the health industry. Nanomaterials are able to cross biological membranes and access cells, tissues and organs that larger-sized particles normally cannot. Nanomaterials can gain access to the blood stream via inhalation or ingestion. This may lead to both genotoxicity and biochemical toxicity. In this review we try to show which types, sizes and concentrations of nanoparticles are safe for human use and this will help in developing diagnostic, prognostic and therapeutic models using nanoparticles. PMID- 27683400 TI - Thyroid-Stimulating Hormone Within Normal Range Does Not Affect Bone Turnover in Euthyroid Postmenopausal Women with Osteoporotic Fracture - A Preliminary Report. AB - BACKGROUND: Pathogenic role of TSH suppression in the damaged bone tissue, in contrast to increased concentrations of thyroid hormones is still unknown. The aim of study was to evaluate the relationship between serum TSH and biochemical bone turnover markers in postmenopausal women with normal thyroid function and to answer whether the differences in TSH concentration within reference range may affect bone metabolism. MATERIAL AND METHODS: 34 women (60-93 years old) admitted to the hospital after osteoporotic fracture participated in the study. Serum propeptide of type 1 procollagen (P1NP) as a bone formation marker and crosslinked C-terminal telopeptides (CTX-I), as a bone resorption marker and TSH were assayed. RESULTS: Median P1NP (p=0,05) was significantly higher in the 1st tertile of TSH values (0,35-1,88 mlU/mL). In the 3rd tertile of TSH concentrations (3,42-4,94 mlU/mL), the highest CTX-I value was found that exceed the reference range for age. No differences were found in bone markers between a group of euthyroid and a group of subjects with TSH<0,35 mlU/mL. No relationship was observed between TSH and bone formation and resorption markers in the whole group of euthyroid postmenopausal women, however bone formation was found to be in the lower reference range for age in the euthyroid subjects as well as in these with decreased TSH. Weight and BMI correlated negatively with CTX (r=-0,68 p<0,03) in fractured women in the 1st tertile of TSH. CONCLUSION: We found no consistent evidence that TSH concentrations within reference range was associated with changes in bone turnover markers. PMID- 27683401 TI - Significance of K(L/V)WX(I/L/V)P Epitope of the B2Gpi in Its (Patho)Physiologic Function. AB - beta2-glycoprotein I (beta2GPI) is a major autoantigen of autoimmune thrombophilia, known as the antiphospholipid syndrome. The exact mechanism underlying the beta2GPI's involvement in the disease is not fully elucidated, as it is not its physiological role. We used random phage peptide library to identify sequences binding to beta2GPI. Obtained K(L/V)WX(I/L/V)P motif, primarily designated as target unrelated, was confirmed as the selective binder of beta2GPI. Based on this motif we confirmed the previously suggested role of polar residues in beta2GPI interactions, and identified some already known and some new putative beta2GPI binding proteins. The latter can help to further elucidate beta2GPI's (patho)physiological role. PMID- 27683402 TI - Severe Hyponatremia with Hypouricemia in a Patient with Medullary Hemorrhage: A Case Report. AB - Hyponatremia is the commonest electrolyte abnormality in hospitalized patients and occurs due to various causes. Here we present a case of SIADH who was diagnosed using commonly available biochemical tests. This case report also discusses the interaction of the laboratory physician with the treating clinician and the approach needed to arrive at a correct diagnosis. It highlights the importance of serum uric acid and fractional excretion of urinary uric acid in the diagnosis of SIADH. It also discusses the approach needed to distinguish SIADH from Cerebral Salt wasting syndrome, where the presenting feature is also hyponatremia. PMID- 27683403 TI - Reference Intervals of Common Clinical Chemistry Analytes for Adults in Hong Kong. AB - BACKGROUND: Defining reference intervals is a major challenge because of the difficulty in recruiting volunteers to participate and testing samples from a significant number of healthy reference individuals. Historical literature citation intervals are often suboptimal because they're be based on obsolete methods and/or only a small number of poorly defined reference samples. METHODS: Blood donors in Hong Kong gave permission for additional blood to be collected for reference interval testing. The samples were tested for twenty-five routine analytes on the Abbott ARCHITECT clinical chemistry system. Results were analyzed using the Rhoads EP evaluator software program, which is based on the CLSI/IFCC C28-A guideline, and defines the reference interval as the 95% central range. RESULTS: Method specific reference intervals were established for twenty-five common clinical chemistry analytes for a Chinese ethnic population. The intervals were defined for each gender separately and for genders combined. Gender specific or combined gender intervals were adapted as appropriate for each analyte. CONCLUSION: A large number of healthy, apparently normal blood donors from a local ethnic population were tested to provide current reference intervals for a new clinical chemistry system. Intervals were determined following an accepted international guideline. Laboratories using the same or similar methodologies may adapt these intervals if deemed validated and deemed suitable for their patient population. Laboratories using different methodologies may be able to successfully adapt the intervals for their facilities using the reference interval transference technique based on a method comparison study. PMID- 27683404 TI - The Effect Size: Beyond Statistical Significance. PMID- 27683405 TI - Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention. AB - OBJECTIVE: Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI), although the exact mechanisms are unclear. We explored the effects of nitrite on reperfusion-induced inflammation, by assessing the levels of specific pro-inflammatory mediators, chemokines and adhesion molecules in plasma and circulating cell subtypes as exploratory end points in the NITRITE-AMI cohort. METHODS: Peripheral blood leucocyte subsets, cell adhesion molecules, high-sensitivity C reactive protein (hs-CRP), the monocyte and neutrophil chemoattractants CCL2 and CXCL1, CXCL5, respectively were measured in the blood of patients who received either intracoronary sodium nitrite (N=40) or placebo (N=40) during PPCI for AMI. Major adverse cardiac events were recorded at 3 years post-PPCI. RESULTS: In the placebo-treated patients, total circulating neutrophil numbers and levels of hs-CRP were raised postreperfusion and then decreased over time; in nitrite-treated patients these changes were suppressed compared with placebo up to 6 months post-PPCI (p<0.01). This effect was associated with reduced expression of neutrophil CD11b, plasma CXCL1, CXCL5 and CCL2 levels (p<0.05). There were no differences in the number of other any other leucocyte population measured (monocytes and lymphocytes) or activation markers expressed by these cells between the treatment groups. These effects were associated with a reduction in both microvascular obstruction and infarct size. CONCLUSIONS: Important reductions in neutrophil numbers and activation post-PPCI in patients with ST elevated myocardial infarction were associated with nitrite treatment, an effect we propose likely underlies, at least in part, the beneficial effects of nitrite upon infarct size. TRIAL REGISTRATION NUMBER: NCT01584453. PMID- 27683406 TI - Impedance to retrograde and forward flow in chronic mitral regurgitation and the physiology of a double outlet ventricle. AB - OBJECTIVE: Mitral regurgitation (MR) is generally characterised as exhibiting a 'low impedance leak into the left atrium'. This notion is widely accepted without measured impedance data. The aim of this study was to define the impedance to retrograde and forward blood flow and to examine hydraulic (pressure-volume) and mechanical (stress-shortening) function in chronic severe MR. METHODS: A mathematical model of a double outlet ventricle was developed and the ratio of retrograde to forward impedance was plotted over a wide range of regurgitant fraction (RF). The model predicts that an impedance ratio >1 indicates that the impedance to retrograde flow exceeds that of forward flow. Left ventricular (LV) systolic pressure/flow rate was used as an index of impedance (mm Hg/mL/s). Data from 10 patients with severe MR were used to assess the clinical applicability of the model. All patients had degenerative valve disease with partial flail leaflet, an RF >50% and an ejection fraction (EF) >0.60. There were seven males and three females, aged 59+/-10. LV volumes as well as retrograde and forward flow rates were determined with echocardiographic and Doppler techniques. RESULTS: The model indicates that the impedance ratio is >1 when the RF ranges from zero to 57%. Clinical data: end-diastolic volume=184+/-47 mL; EF=0.63+/-3%; RF=53+/-4%. Values for retrograde and forward impedance were 0.77+/-0.17 and 0.63+/-0.12 (p=0.003); the impedance ratio was 1.22+/-0.19. Total impedance to LV emptying was low (0.35+/-0.06). The ratio of systolic wall stress to EF (580+/-81 g/cm2) was normal. Data are mean+/-SD. CONCLUSIONS: The model, supported by clinical data, indicates that the impedance to retrograde flow exceeds the impedance to forward flow in chronic severe MR. These findings refute the notion of a low impedance leak into the left atrium. The double outlet of an enlarged ventricle provides a mechanism for low total impedance to ejection in the presence of a normal stress-shortening relation. PMID- 27683407 TI - Estimating cancer risk from invasive cardiac procedures in children. PMID- 27683408 TI - Role of Social Media and the Internet in Education. AB - Since the advent of the Internet, and in particular the development of the interactive version of the web, Web 2.0, use of Social Media has developed into a major strategy for businesses and organizations such as the IFCC to use for the purposes of Public Relations and Education. The early Internet 'Web 1.0' was a largely static environment which did not allow interaction between organizations and their customers and/or members and as such was mainly used as an information repository rather than a dynamic environment for the exchange of ideas and active marketing and education. Since the development of Web 2.0 we have seen a massive increase in web based traffic which could be loosely called 'social networking' which initially was mainly networking between individuals but more recently has developed into a major marketing resource allowing networking between organizations and individuals on the web. It follows then that by developing a Social Media presence on platforms such as Facebook, LinkedIn, Twitter and other social media sites organizations can use this networking for the purposes of marketing, public relations, and in the case of IFCC, education of members and other interested individuals across the globe. PMID- 27683409 TI - Critical Appraisal of Microbiology Guidelines Endorsed by two Professional Organisations: Societe Francaise De Microbiologie (SFM) and American Society of Microbiology (ASM). AB - Medical practice guidelines (GLs) being tools that are mainly designed to evaluate medical professionals, it sounds logical, and fair, that professionals should in turn evaluate GLs. Microbiology being a medical discipline, we used the AGREE instrument, i.e. an established evaluation tool for GLs, in order to evaluate the quality of two major microbiology guidelines, i.e. the SFM GLs and the ASM GLs). Both guidelines remain sub-optimal in their levels of quality, and obtain scores that are not very different from the average scores obtained by many other guidelines in various medical disciplines. We therefore believe that both guidelines need to be modified before they can be recommended without provisos. A higher degree of multi-disciplinary work, including a more formal implication of methodologists, as well as of infectious disease clinicians, and of economists, might perhaps enable future editions of these guidelines to reach higher levels of quality. PMID- 27683410 TI - Pitfalls in the Measurements and Assesment of Glomerular Filtration Rate and How to Escape them. PMID- 27683412 TI - Congenital Hyperferritinemia Diagnosed in A 2 Month Old-A Case Report from India. AB - BACKGROUND: In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. METHOD: We report a case of congenital hyperferritinemia with serum iron within reference range, along with bronchopneumonia, acyanotic congenital heart disease, anemia, hypocalcaemia and dysmorphism in a 2 month old baby. Symptomatic treatment was given. RESULT: The baby was discharged after 7 days. In a stable condition and having gained some weight.He was diagnosed as a case of congenital hyperferritinemia as C reactive protein levels normalized but ferritin levels remained high and A37C mutation within the iron-responsive element of L-ferritin was detected. He was born to consanguineous parents, there was history of cataract in the family and his mother also had high serum ferritin levels. CONCLUSION: This case is an example of the detection of a rare genetic disorder in a child admitted with apparently innocuous symptoms of fever and inflammation. Our case underlines the importance of monitoring ferritin levels, along with other signs of inflammation in order to differentiate congenital hyperferritinemia from inflammatory cause. PMID- 27683411 TI - Potential Markers in Cardiac Hypertrophy? AB - Cardiomyopathies are diagnosed based on medical history of patient (symptoms and family history), physical examination, results of echocardiogram and in some situations additionally ECG or chest-X-ray results. Currently used non-invasive diagnostic methods, could be complemented by biochemical tests. In this review some emerging potential biomarkers such as: osteopontin, ST-2 receptor, osteoprotegerin, neopterin, urocortins, growth differentiation factor 15 and urotensin II are described. In current article human and non human investigations have been reviewed, since rat is most commonly used model in experimental cardiology and gives important foundations to clinical knowledge. PMID- 27683413 TI - The Laboratory's Role in Opioid Pain Medication Monitoring. AB - Opioid analgesics are the most potent pain medications therefore they are often used for the treatment of chronic malignant and non-malignant pain. Their strong addictive potential requires close monitoring of patients on opioid therapy for possible non-compliance with prescriptions, for drug diversion, and for proof of avoidance of non-prescribed or illicit opioids. Monitoring can be performed by urine drug screens or qualitative or quantitative drug confirmation assays. Natural, semi-synthetic and synthetic opioids have dissimilar chemical structures and they undergo extensive metabolism. Phase one metabolic reactions of opioids can produce other opioids with similar structures to other, non-prescribed medications. Only detailed and concurrent analysis of parent drugs and metabolites can provide accurate clinical information regarding patient compliance. Traditional immunoassays, often used for urine drug screening, react with only a small number of opioids or only with a single medication and they exhibit variable cross reactivity with their phase two metabolites. Additionally the limit of detection of these immunoassays may not be sufficient for medical purposes, therefore clinical interpretation of immunoassay test results can be challenging. Recently liquid chromatography, mass spectrometry (LCMSMS) based assays have been adapted by many clinical laboratories. These LCMSMS tests can provide information about the presence of several opioids and their metabolites in a single sample at clinically meaningful detection limits, allowing accurate assessment of patient compliance. This review article will investigate in details the various opioids, their metabolism and the challenges the testing laboratories and ordering clinicians face. PMID- 27683414 TI - The EMT transcription factor Zeb2 controls adult murine hematopoietic differentiation by regulating cytokine signaling. AB - Epithelial-to-mesenchymal-transition (EMT) is critical for normal embryogenesis and effective postnatal wound healing, but is also associated with cancer metastasis. SNAIL, ZEB, and TWIST families of transcription factors are key modulators of the EMT process, but their precise roles in adult hematopoietic development and homeostasis remain unclear. Here we report that genetic inactivation of Zeb2 results in increased frequency of stem and progenitor subpopulations within the bone marrow (BM) and spleen and that these changes accompany differentiation defects in multiple hematopoietic cell lineages. We found no evidence that Zeb2 is critical for hematopoietic stem cell self-renewal capacity. However, knocking out Zeb2 in the BM promoted a phenotype with several features that resemble human myeloproliferative disorders, such as BM fibrosis, splenomegaly, and extramedullary hematopoiesis. Global gene expression and intracellular signal transduction analysis revealed perturbations in specific cytokine and cytokine receptor-related signaling pathways following Zeb2 loss, especially the JAK-STAT and extracellular signal-regulated kinase pathways. Moreover, we detected some previously unknown mutations within the human Zeb2 gene (ZFX1B locus) from patients with myeloid disease. Collectively, our results demonstrate that Zeb2 controls adult hematopoietic differentiation and lineage fidelity through widespread modulation of dominant signaling pathways that may contribute to blood disorders. PMID- 27683417 TI - Microfluidic Chips for Semen Analysis. AB - The gold standard of semen analysis is still an manual method, which is time consuming, labour intensive and needs thorough quality control. Microfluidics can also offer advantages for this application. Therefore a first step in the development of a microfluidic chip has been made, which enables the man the semen analysis at home. In this article recent efforts to determine the concentration and motility using a microfluidic chip are summarized. PMID- 27683415 TI - C1q and HMGB1 reciprocally regulate human macrophage polarization. AB - A healthy immune system results from a balance of stimulatory and inhibitory pathways that allow effective responses to acute insults, without descending into chronic inflammation. Failed homeostasis is characteristic of autoimmune diseases such as systemic lupus erythematosus. Although HMGB1 induces proinflammatory M1 like macrophage differentiation, we describe a mechanism by which C1q modulates this activity and collaborates with HMGB1 to induce the differentiation of monocytes to anti-inflammatory M2-like macrophages. These anti-inflammatory macrophages are unresponsive to dendritic cell induction factors, effectively removing them from participation in an adaptive immune response. This pathway is mediated through a complex with RAGE and LAIR-1 and depends on relative levels of C1q and HMGB1. Importantly, these data provide insight into a homeostatic mechanism in which C1q and HMGB1 can cooperate to terminate inflammation, and which may be impaired in C1q-deficient patients with autoimmune disease. PMID- 27683418 TI - Miniaturization for Point-of-Care Analysis: Platform Technology for Almost Every Biomedical Assay. AB - Platform technologies for the changing need of diagnostics are one of the main challenges in medical device technology. From one point-of-view the demand for new and more versatile diagnostic is increasing due to a deeper knowledge of biomarkers and their combination with diseases. From another point-of-view a decentralization of diagnostics will occur since decisions can be made faster resulting in higher success of therapy. Hence, new types of technologies have to be established which enables a multiparameter analysis at the point-of-care. Within this review-like article a system called Fraunhofer ivD-platform is introduced. It consists of a credit-card sized cartridge with integrated reagents, sensors and pumps and a read-out/processing unit. Within the cartridge the assay runs fully automated within 15-20 minutes. Due to the open design of the platform different analyses such as antibody, serological or DNA-assays can be performed. Specific examples of these three different assay types are given to show the broad applicability of the system. PMID- 27683419 TI - Recent Developments in Miniaturized PCR-Microchips, Microarrays and Microdroplets. AB - Microminiaturization of assays and lab-on-a-chip devices hold considerable promise for the future of analysis, especially in point-of-care testing. This article focuses on developments that have occurred during the last five years in the specific area of microchip PCR and miniaturized PCR in arrays of reaction vessels and droplets. Although, this area continues to be an active focus of research and development and the variety and ingenuity of microchip PCR and integrated microchip PCR devices continue to increase, commercialization lags behind the progress being made in digital PCR and arrays for real-time PCR. PMID- 27683416 TI - Prolyl-4-hydroxylase 2 and 3 coregulate murine erythropoietin in brain pericytes. AB - A classic response to systemic hypoxia is the increased production of red blood cells due to hypoxia-inducible factor (HIF)-mediated induction of erythropoietin (EPO). EPO is a glycoprotein hormone that is essential for normal erythropoiesis and is predominantly synthesized by peritubular renal interstitial fibroblast like cells, which express cellular markers characteristic of neuronal cells and pericytes. To investigate whether the ability to synthesize EPO is a general functional feature of pericytes, we used conditional gene targeting to examine the von Hippel-Lindau/prolyl-4-hydroxylase domain (PHD)/HIF axis in cell expressing neural glial antigen 2, a known molecular marker of pericytes in multiple organs. We found that pericytes in the brain synthesized EPO in mice with genetic HIF activation and were capable of responding to systemic hypoxia with the induction of Epo. Using high-resolution multiplex in situ hybridization, we determined that brain pericytes represent an important cellular source of Epo in the hypoxic brain (up to 70% of all Epo-expressing cells). We furthermore determined that Epo transcription in brain pericytes was HIF-2 dependent and cocontrolled by PHD2 and PHD3, oxygen- and 2-oxoglutarate-dependent prolyl-4 hydroxylases that regulate HIF activity. In summary, our studies provide experimental evidence that pericytes in the brain have the ability to function as oxygen sensors and respond to hypoxia with EPO synthesis. Our findings furthermore suggest that the ability to synthesize EPO may represent a functional feature of pericytes in the brain and kidney. PMID- 27683420 TI - Future Prospects in Breast Cancer Research - Cancer Stem Cells. AB - Breast cancer is one of the leading causes of cancer deaths among women. Although significant advances in the prevention, diagnosis and management are made, still every year half a million women die of breast cancer. Personalised treatment has the potential to increase treatment efficacy, and hence decrease mortality rates. Moreover, understanding cancer biology and translating this knowledge to the clinic, will improve the breast cancer therapy regime tremendously. Recently, it has been proposed that cancer stem cells (CSC) play an important role in tumour biology. CSC have the ability for self-renewal and are pivotal in setting the heterogeneous character of a tumour. Additionally, CSC possess several characteristics that make them resistant and more aggressive to the conventional chemo- and radiotherapy. Nowadays, breast cancer therapy is focused on killing the differentiated tumour cells, leaving the CSC unharmed, potentially causing recurrence of the disease and metastasis. Specific targeting of the CSC will improve the disease-free survival of breast cancer patients. In this article, two methods are described, aiming at specifically attacking the differentiated tumour cells ('Apoptosis chip') and the cancer stem cell. For this, microfluidics is used. PMID- 27683422 TI - Biomarkers Beyond the Natriuretic Peptides for Chronic Heart Failure: Galectin-3 and Soluble ST2. AB - B-type natriuretic peptide (BNP) and NT-proBNP are widely used plasma biomarkers for the diagnosis of acute decompensated heart failure and prognosis for future cardiac disease. The clinical performance of these tests for management of chronic heart failure is somewhat limited by the markers' high biological variation. Biomarkers such as galectin-3 and soluble ST2 that reflect ongoing remodeling via cardiac fibrosis of the heart may provide complementary information to the natriuretic peptides in the management of chronic heart failure with regards to risk stratification for future adverse cardiac events (death, myocardial infarction, and need for heart transplantation). However, implementation of these biomarkers into routine clinical practice requires documentation that these tests will enable therapeutic decisions that can be made to improve clinical outcomes, and the availability of commercial assays. This report will discuss the need for novel heart failure biomarkers, ideal characteristics of assays, and review and compare the clinical performance of assays for galectin-3 and sST2 for chronic heart failure disease management. PMID- 27683421 TI - Metastasis and Circulating Tumor Cells. AB - Cancer is a prominent cause of death worldwide. In most cases, it is not the primary tumor which causes death, but the metastases. Metastatic tumors are spread over the entire human body and are more difficult to remove or treat than the primary tumor. In a patient with metastatic disease, circulating tumor cells (CTCs) can be found in venous blood. These circulating tumor cells are part of the metastatic cascade. Clinical studies have shown that these cells can be used to predict treatment response and their presence is strongly associated with poor survival prospects. Enumeration and characterization of CTCs is important as this can help clinicians make more informed decisions when choosing or evaluating treatment. CTC counts are being included in an increasing number of studies and thus are becoming a bigger part of disease diagnosis and therapy management. We present an overview of the most prominent CTC enumeration and characterization methods and discuss the assumptions made about the CTC phenotype. Extensive CTC characterization of for example the DNA, RNA and antigen expression may lead to more understanding of the metastatic process. PMID- 27683423 TI - A Complement for the WHO Laboratory Manual for the Examination and Processing of Human Semen (First Edition, 2010). PMID- 27683424 TI - Risk Factors for Graft Loss in Pediatric Renal Transplant Recipients After Transfer of Care. AB - BACKGROUND: Improvements in transplantation have increased the survival of children after kidney transplantation. These patients have complex needs, and the current medical system is not prepared to effectively transfer the care of these individuals from pediatric to adult health-care systems. Too often, transfer occurs during moments of crisis and is associated with poor outcomes. OBJECTIVE: The aim of this study was to use a national database, the Scientific Registry of Transplant Recipients, to test the hypothesis that the increased risk of graft loss after transfer of care (from pediatric to adult services) for young adult kidney transplant recipients over a 2- to 3-year posttransfer follow-up period was related to these posttransfer risk factors (medication noncompliance, acute rejection, insurance status). DESIGN: A retrospective, longitudinal, correlational design using secondary data was used to evaluate the transfer of care of 250 kidney transplant recipients (ages 16-25). RESULTS: Seventy-seven (30.8%) individuals lost their graft within 3 years after transfer of care. Medication noncompliance, acute rejection, and serum creatinine >2.0 mg/dL at transfer were significant predictors of graft loss after accounting for multiple other factors. CONCLUSION: These individuals are at risk for graft loss after transfer of care and may benefit from increased personalized care during this risky period. PMID- 27683426 TI - Flow Cytometry in the Diagnosis of Myelodysplastic Syndromes. AB - Myelodysplastic syndromes are clonal hematopoietic stem cell disorders. Their exact etiology is unknown. Myelodysplastic syndromes cause progressive bone marrow failure resulting in pancytopenia and refractory, transfusion-dependent anemia. One can observe typical morphological alterations in the erythroid, myeloid and/or megakaryocytic cell lineage. Blast counts may also be increased. The pathologic cells are genetically unstable, and a myelodysplastic syndrome might transform into acute myeloid leukemia. The overall survival of these diseases range between few months to around ten years. Correct diagnosis and accurate prognostic classification is essential. In the past decades several scoring systems were established beginning with the French-American-British classification to the most recent Revised International Prognostic Scoring System. In all of these classifications bone marrow morphology is still the most important factor, though nowadays the genetic aberrations and flow cytometry findings are also included. The diagnosis and prognostic classification of myelodysplastic syndromes remain a great challenge for hematologists. PMID- 27683425 TI - Brain activation for spontaneous and explicit false belief tasks overlaps: new fMRI evidence on belief processing and violation of expectation. AB - There is extensive discussion on whether spontaneous and explicit forms of ToM are based on the same cognitive/neural mechanisms or rather reflect qualitatively different processes. For the first time, we analyzed the BOLD signal for false belief processing by directly comparing spontaneous and explicit ToM task versions. In both versions, participants watched videos of a scene including an agent who acquires a true or false belief about the location of an object (belief formation phase). At the end of the movies (outcome phase), participants had to react to the presence of the object. During the belief formation phase, greater activity was found for false vs true belief trials in the right posterior parietal cortex. The ROI analysis of the right temporo-parietal junction (TPJ), confirmed this observation. Moreover, the anterior medial prefrontal cortex (aMPFC) was active during the outcome phase, being sensitive to violation of both the participant's and agent's expectations about the location of the object. Activity in the TPJ and aMPFC was not modulated by the spontaneous/explicit task. Overall, these data show that neural mechanisms for spontaneous and explicit ToM overlap. Interestingly, a dissociation between TPJ and aMPFC for belief tracking and outcome evaluation, respectively, was also found. PMID- 27683427 TI - Prediction of Therapy Response and Prognosis in Leukemias by Flow Cytometric MDR Assays. AB - Multidrug resistance (MDR) is an unwanted phenomenon, that may cause therapy failure in several neoplasms including hematological malignancies. The purpose of any type of laboratory MDR assay is to reliably identify such patients and to provide useful data to clinicians with a relatively short turnaround time. MDR can be multicausal and several previous data identified a group of transmembrane proteins - the ATP-binding casette (ABC) proteins - that may be involved in MDR in various hematological malignancies. The prototype of these proteins is the P glycoprotein (Pgp, MDR1, ABCB1) that is a seven-membrane spanning transmembrane protein capable of extruding several cytotoxic drugs that are of key importance in the treatment of hematological disorders. Similarly other ABC proteins - Multidrug resistance associated protein 1 (ABCC1) and breast cancer resistance protein (ABCG2) are both capable of pumping out cytotoxic drugs. Here, we present flow cytometric methods to identify MDR proteins by antigen and activity assays. The advantage of flow technology is the short turnaround time and its relative easiness compared to nucleic acid based technologies. However, for the activity assays, it should be noted, that these functional tests require live cells, thus adequate results can only be provided if the specimen transport can be completed within 6 hours of sample collection. Identification of MDR proteins provides prognostic information and may modulate therapy, thus signifies a clinically useful information in the evaluation of patients with leukemias. PMID- 27683428 TI - Flow Cytometric Investigation of Classical and Alternative Platelet Activation Markers. AB - Platelets show a substantial role in the maintenance of vascular integrity when these cells after a rapid activation adhere to the vessel wall lesion, aggregate with other platelets and leukocytes resulting in an arterial thrombosis. Analysis of in vivo platelet activation at an early time point is crucial in the detection of developing thrombotic events. In addition, the forecast of future complications as well as the evaluation of the efficacy of anti- platelet medication are also essential in a large group of patients. Changes in the levels of platelet receptors or alteration in other surface properties due to intra- and extracellular responses to a stimulus can be measurable primarily by flow cytometry with specific antibodies via the assessment of classical and alternative platelet activation markers. Some of these biomarkers have been already used in routine laboratory settings in many cases, while others still stand in the phase of research applications. Deficiency in platelet receptors is also accessible with this technique for the diagnosis of certain bleeding disorders. We here describe the most important types of platelet activation markers, and give an overview how the levels of these markers are altered in different diseases. PMID- 27683429 TI - Measurement of Soluble Biomarkers by Flow Cytometry. AB - Microparticle based flow cytometric assays for determination of the level of soluble biomarkers are widely used in several research applications and in some diagnostic setups. The major advantages of these multiplex systems are that they can measure a large number of analytes (up to 500) at the same time reducing assay time, costs and sample volume. Most of these assays are based on antigen antibody interactions and work as traditional immunoassays, but nucleic acid alterations - by using special hybridization probes -, enzyme- substrate or receptor-ligand interactions can be also studied with them. The applied beads are nowadays provided by the manufacturers, but cheaper biological microbeads can be prepared by any user. One part of the systems can be used on any research or clinical cytometers, but some companies provide dedicated analyzers for their multiplex bead arrays. Due to the high standardization of the bead production and the preparation of the assay components the analytical properties of these assays are quite reliable with a wide range of available applications. Cytokines, intracellular fusion proteins, activated/phosphorylated components of different signaling pathways, transcription factors and nuclear receptors can be identified and quantitated. The assays may serve the diagnostics of autoimmune disorders, different viral and bacterial infections, as well as genetic alterations such as single nucleotide polymorphisms, small deletions/insertions or even nucleotide triplet expansions can be also identified. The most important principles, technical details and applications of these systems are discussed in this short review. PMID- 27683430 TI - Calcium Influx Characteristics During T Lymphocyte Activation Measured with Flow Cytometry. AB - T lymphocytes are of paramount importance in many intercellular reactions, such as the regulation of the inflammatory response and immune reactivity. Until the recent past, single-cell techniques were used for the investigation of calcium influx during T lymphocyte activation. Therefore, over the recent years we have created a novel approach that allows simultaneous recording of calcium influx in several lymphocyte subsets using flow cytometry. Our research group developed a robust algorithm (FacsKin) for the evaluation of the acquired data that fits functions to median values of the fluorescent marker of interest and calculates relevant parameters describing each function. Over the recent years, we have investigated calcium influx characteristics applying this method in a number of autoimmune disorders and under different physiological conditions (such as the neonatal period and pregnancy). In this review, we aim to give a brief summary of our findings and of the common characteristics of calcium influx in the investigated disorders, namely: multiple sclerosis (MS), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), ankylosing spondylitis (AS), and preeclampsia (PE). Based on our results, a number of dominant features were identified that were present in most of the investigated autoimmune diseases. PMID- 27683431 TI - Advances in Oral Coagulants. AB - This article reviews current and future treatment practices concerning oral anticoagulants. In the second decade of the 21st millennium clinicians can finally treat thrombotic disease with long-awaited new oral anticoagulant medications. In addition, improvements have been made in managing warfarin, the traditional but far from obsolete medication. The first part of this review will cover current advances with warfarin treatment. The second portion will discuss specific active coagulation factor inhibitors, the new oral anticoagulants. PMID- 27683432 TI - Education & Training in Laboratory Medicine in the United States. PMID- 27683433 TI - A Review of Bachelor's Degree Medical Laboratory Scientist Education and Entry Level Practice in the United States. AB - The baccalaureate degree is generally the degree that provides the laboratory professional with the greatest level of general scientific background, training, job flexibility, and advancement opportunities. It is widely considered the requirement for entry-level work in the field of medical laboratory science, especially for those that covet work in management or specialty areas. This paper focuses on the educational models and levels of practice for MLS professionals including the entry level competencies of new professionals at the baccalaureate level. The accreditation of MLS programs and professional certification serve as important quality management systems to ensure program quality and professional competency prior to the start of entry level work. PMID- 27683434 TI - Post-Baccalaureate Laboratory Specialist Certifications and Master's Degrees in Laboratory Medicine. AB - Opportunities to advance one's knowledge and position are available within the clinical laboratory arena. By obtaining a specialist credential in chemistry, hematology or microbiology, a laboratorian has demonstrated advance knowledge and ability in their respective discipline. These specialist certifications open doors within and outside the laboratory profession and may lead to promotion. The specialist in blood banking credential is unique in that accredited training programs are available, some of which are affiliated with universities and graduate credit is granted for program completion. Other avenues available include pathologist assistants programs, diplomats in laboratory management and Master of Science degrees in clinical laboratory science. There are a number of choices available to achieve your professional goal. PMID- 27683435 TI - Postdoctoral Professional Fellowships in Laboratory Medicine. AB - Doctoral level scientists often pursue a traditional academic route, focusing their efforts on research and education. However, additional options exist for those that are interested in using their laboratory and research skills in a clinical setting. Clinical laboratory directors serve as the interface between the clinical laboratory and the users of laboratory test results. This article describes these career paths options for PhD scientists. Clinical laboratory directors are primarily trained via one of two routes: physicians that have been trained in clinical pathology or non-physician doctoral scientists that have completed professional fellowship training. This article will focus on the latter of these 2 routes. In the United States, completing a postdoctoral fellowship in laboratory-specific professional fields qualifies non-physician doctoral scientists as laboratory directors and consultants. Their expert consultation provides invaluable insight into testing procedures such as possible sources of interference or inaccurate test results, preferred testing for specific clinical situations, and confirmatory methods. They must also be knowledgeable about current instrumentation, assay limitations, and the newest available technologies. One of the older and more developed professional fellowships in the United States, clinical chemistry, encompasses many laboratory disciplines and will be highlighted in detail. Training information specific to clinical immunology, clinical microbiology, and clinical genetics is also discussed. PMID- 27683436 TI - An Overview of United States Physician Training, Certification, and Career Pathways in Clinical Pathology (Laboratory Medicine). AB - Clinical Pathology (CP) - also known as Laboratory Medicine - is a rewarding and yet under-recognized career option for United States (U.S.) and international medical school graduates. The present article outlines the training pathway toward becoming a clinical pathologist in the U.S, including undergraduate, graduate, and post-graduate phases of training. As the current state of CP residency training in the U.S. is the result of decades of curriculum reform, that progression is briefly reviewed to provide context for the shift toward competency-based education during residency and beyond. Options for fellowship training in CP subspecialties, as well as the current emphasis on Maintenance of Certification (MOC) and Maintenance of Licensure (MOL) are also discussed. This article concludes with a general overview of career pathways and options for those with CP training. PMID- 27683437 TI - The Development of the Doctorate in Clinical Laboratory Science in the U.S. AB - In the United States, a new post-baccalaureate degree has been introduced in the medical laboratory sciences profession whose hallmark is advanced clinical practice beyond that of the entry level generalist. After more than a decade of exploring the most appropriate level of education and training in laboratory medicine to meet the demands of a changing health care system, the first Doctorate of Clinical Laboratory Science (DCLS) program is now offered. This article discusses the collaborative effort among professional organizations and stakeholders to develop the framework for the DCLS degree. In addition, the roles, responsibilities and justification for need of the DCLS are presented along with accreditation standards for DCLS programs and future challenges for this new member of the health care delivery team. PMID- 27683438 TI - Cell Culture Models and Pharmacological Perspective for the Study of Breast Cancer Markers. AB - Among the most prevalent neoplasias, breast cancer shows an astonishing tendency. Unfortunately this cancer has a high mortality worldwide, requiring sustained management of all actors involved in public health in order to get an early diagnosis and treatment. The methods associated with conventional cytogenetics and molecular cell culture, besides early detection of gene expression patterns associated with cancer susceptibility, have contributed to identify inherited genes and metabolic disorders related to obesity, which are also involved in breast cancer. In any case, a broad study of the above mentioned factors can give a predictive value to support the design of public health models to determine cancer risk in order to decrease the mortality from this disease. (1) Cell cultures offers a wide range of scientific approach for the study of breast cancer, including the analysis of biological function of several compounds in search of increasingly effective treatments with fewer side effects against this malignancy. (2). PMID- 27683439 TI - Establishment of Biological Reference Intervals and Reference Curve for Urea by Exploratory Parametric and Non-Parametric Quantile Regression Models. AB - BACKGROUND: The validity of the entire renal function tests as a diagnostic tool depends substantially on the Biological Reference Interval (BRI) of urea. Establishment of BRI of urea is difficult partly because exclusion criteria for selection of reference data are quite rigid and partly due to the compartmentalization considerations regarding age and sex of the reference individuals. Moreover, construction of Biological Reference Curve (BRC) of urea is imperative to highlight the partitioning requirements. MATERIALS AND METHODS: This a priori study examines the data collected by measuring serum urea of 3202 age and sex matched individuals, aged between 1 and 80 years, by a kinetic UV Urease/GLDH method on a Roche Cobas 6000 auto-analyzer. RESULTS: Mann-Whitney U test of the reference data confirmed the partitioning requirement by both age and sex. Further statistical analysis revealed the incompatibility of the data for a proposed parametric model. Hence the data was non-parametrically analysed. BRI was found to be identical for both sexes till the 2(nd) decade, and the BRI for males increased progressively 6(th) decade onwards. Four non-parametric models were postulated for construction of BRC: Gaussian kernel, double kernel, local mean and local constant, of which the last one generated the best-fitting curves. CONCLUSION: Clinical decision making should become easier and diagnostic implications of renal function tests should become more meaningful if this BRI is followed and the BRC is used as a desktop tool in conjunction with similar data for serum creatinine. PMID- 27683440 TI - Cystatin C in Acute Coronary Syndrome. AB - Cystatin C has been regarded as a novel sensitive marker for the assessment of renal function, and the role of cystatin C as a predictor of cardiovascular events in patients with impaired renal function has been confirmed in clinical studies. In this study we assessed the association between cystatin C and Coronary artery disease [CAD] in a consecutive series of patients with normal kidney function in order to avoid the well-known effect of overt renal insufficiency on coronary atherosclerosis, and evaluate whether cystatin C has an ability to identify individuals at a higher risk for CAD among patients belonging to a low-risk category according to estimated glomerular filtration rate .The current study and review of literature demonstrated that serum levels of cystatin C, were independently associated with the development of CAD. PMID- 27683442 TI - Pharmacogenomics and Theranostics in Practice: A summary of the Euromedlab-ESPT (The European Society of Pharmacogenomics and Theranostics) satellite symposium, May 2013. PMID- 27683441 TI - NT-proBNP: A Guide to Improve the Management of Patients with Heart Failure. AB - N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a versatile biomarker, that has been extensively studied in large cohorts of individuals in the general population, in subjects at risk for developing left ventricular dysfunction and cardiovascular events, and in patients with chronic or acutely decompensated heart failure (HF). In this paper, the pros and cons of using natriuretic peptide testing to manage patients with HF are presented and discussed over 3 broad areas: (1) dyspnea triage in the emergency room, (2) natriuretic peptide-guided treatment of chronic HF, and (3) management of patients with HF in primary care and nursing homes. PMID- 27683443 TI - Platelet Function Testing-Guided Antiplatelet Therapy. AB - Cardiovascular diseases are the leading cause of death in the Western world. Several factors have led to the increase in vascular disorders, including the aging population, unhealthy lifestyles, increasing rates of diabetes and raised lipids, and further risk factors resulting in inflammation and calcification of the vascular endothelium. Activated platelets in damaged blood vessels can trigger arterial thrombus formation, leading to vascular occlusion with subsequent organ hypoperfusion and clinical manifestation of myocardial infarction, stroke, or peripheral artery disease. Platelet inhibitors such as aspirin and clopidogrel (Plavix((r)) and generics) are prescribed as primary or secondary prevention to attenuate chronic platelet activation. However, a significant proportion of patients do not respond adequately to uniform antiplatelet treatment. These 'non-responders' have an increased risk for stent thrombosis, stroke, and other ischemic complications. Platelet function (PF) tests can identify these patients thus enabling physicians to offer personalized and alternative treatment strategies. Recent alternatives to clopidogrel include prasugrel (Efient((r))) and ticagrelor (Brilique((r))) - that are both more potent than clopidogrel but also more expensive and associated with a higher risk of bleeding complications. Given these drawbacks, PF testing might help clinicians to prescribe optimal antiplatelet agent to maximize patient safety and efficacy while minimizing costs. While randomized studies using different test systems have left clinicians puzzled about the medical value of tailored antiplatelet therapy, accumulated evidence from recent studies on tailored antiplatelet therapies and the association with improved outcomes have now resulted in a consensus expert opinion for the specific adoption of PF diagnostics into clinical practice. PMID- 27683444 TI - Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Emergence of the Solution to an Important Unmet Need. AB - Alzheimer's Disease (AD) represents an increasing problem as the overall population ages. The identification of reliable biomarkers of AD has, therefore, become increasingly important. This is not only for risk prediction and diagnosis in order to provide appropriate care, but also to identify those patients at high risk of AD development who may be eligible for inclusion in clinical trials of novel therapies. Treatment in the early stages of the disease are urgently needed, as these are expected to yield the greatest benefits. The cerebrospinal fluid biomarkers amyloid beta (1-42), hyperphosphorylated Tau and total Tau have been most extensively evaluated. Their combination has been shown to be valuable in identifying AD patients, including those who will progress to AD among a wider group of subjects with only subjective memory complaints or in very early disease stages. While commercially available diagnostic tests for these biomarkers are available, implementation in clinical practice is associated with a number of problems, such as absorption of amyloid beta (1-42) to laboratory tubes, a high degree of batch-to-batch variation with the current test, and the lack of certified reference material. Therefore, there is a need for increased automation and implementation on routine diagnostic platforms in order to support the cost effective and reliable introduction of the tests on a wider scale. As the use of these biomarkers in research and in clinical practice continues to expand, extensive standardisation efforts are being put in place to address the challenges associated with the use of these biomarkers. Together with the development of additional biomarkers for early and differential diagnosis, this casts good foresight to serve the needs of an increasing patient population. PMID- 27683445 TI - Clinical Application of Pharmacogenetics: Where are We Now? AB - Pharmacogenetic (PGx) testing has the potential to improve drug therapy in an individual by informing appropriate drug dosing or drug selection in order to maximize efficacy and safety. Although multiple studies have illustrated the potential benefits of such testing when applied to specific drugs across a broad range of therapy areas, the uptake of PGx testing in routine clinical practice has been relatively limited. Implementation appears to be hampered by the absence of sufficiently strong evidence linking the results of testing with actionable benefits in terms of clinical outcomes. Meanwhile, there are now adequate data to allow dosing recommendations as have been developed by bodies including the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) in several settings, including TPMT/thiopurines, CYP2C19/clopidogrel, CYP2D6/codeine, VKORC1-CYP2C9/warfarin, HLA-B*5701/abacavir, SLCO1B1/simvastatin and HLAB*5801/allopurinol. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) have also recently initiated surveys in order to better understand the extent of, and the role played by, PGx testing in clinical practice. This should help identify where further training and education may be beneficial. To this end, in collaboration with ESPT, the IFCC Pharmacogenetic Laboratory Network has now been formed, with the aim of improving the uptake and quality of PGx testing. PMID- 27683447 TI - Between-Subject Variation of the Within-Subject Biological Variation. PMID- 27683446 TI - The Advance of Personalized and Stratified Therapies in Bronchial Asthma: Phenotypes - Endotypes - Biomarkers. AB - Bronchial asthma (BA) is a chronic inflammatory condition with increasing incidence and prevalence worldwide. BA is currently the most prevalent chronic disease in pediatric patients. The majority of BA patients are therapeutically well controlled with guideline based anti-inflammatory therapies; however, there is also a clinically recognized proportion of patients who do not benefit from currently available medication for several reasons. This is the starting point for further investigation into the complexity of the inflammatory phenotype of BA. Recently, the heterogeneity in terms of cellular and molecular pathways underlying BA has been recognized and established. These different pathogenic mechanisms are defined as 'endotypes'. The best studied endotype so far is the association with T-helper type 2 (TH2) cell eosinophilic airway inflammation. Recently, a number of different therapeutic strategies have been clinically explored which target certain mediators of this pathway, including the interleukins IL-4, IL-5 and IL-13. It is now clear that patients with the TH2 endotype largely benefit from novel biologicals in this area. However, the challenge for diagnostics is to identify patients exhibiting this endotype, and this is the starting point for the search for new biomarkers. One biomarker that has recently been selected based on differential gene expression analysis, and which seems to be strongly associated with the TH2 endotype, is periostin. In this article we will provide a state of the art update on the definition of clinical phenotypes, pathogenetic endotypes and biomarker development for improving BA treatment. PMID- 27683448 TI - Iron Indices in Patients with Functional Anemia in Chronic Kidney Disease. AB - BACKGROUND: Despite high ferritin level, HDCKD patients may have functional iron deficiency even after intravenous iron (iv) therapy. The aim of this study was to test the hypothesis that lowered serum transferrin level may contribute to functional anemia and erythropoietin hypo responsiveness by the failure to transport accumulated tissue iron to the relevant target tissue. MATERIALS AND METHODS: The study subjects were divided into four groups. Group-A: HDCKD Patients receiving iv iron (n=290). Group-B: Patients not initiated on to hemodialysis (NDCKD), and received oral iron (n=38). Group-C: HDCKD patients with erythropoietin hypo responsiveness (n=9). Group-D: Healthy controls (n=36). The group-A, patients were sub-divided into five groups (A-1 to A-5) based on their serum ferritin levels. RESULTS: Serum ferritin and tissue iron levels in group-A and C patients were significantly greater than the group-D(p<0.0001) and group-B patients(p<0.001). Transferrin level of group-A and C showed lowered values and consequently a higher %TSAT when compared to group-D. The percent of patients with iron overload was 2.6%, 31%, and 44% in group-B, group-A and group-C respectively. Serum transferrin level significantly correlated with TIBC in group A and B patients (p<0.0001;p<0.05 respectively). Transferrin level significantly correlated with TIBC in all subgroups of HDCKD(p<0.05) with the exception in subgroup-A2 and with hemoglobin in subgroups A3 (p<0.05) and A5(p<0.01) respectively. CONCLUSIONS: The lowered transferrin level prevents the proper transport of the iron to the hematopoietic sites, which may be a reason for the low hemoglobin synthesis and also for the development of erythropoietin hypo responsiveness in some of the dialysis patients. PMID- 27683449 TI - Stroke-induced blood-brain barrier breakdown along the vascular tree - No preferential affection of arteries in different animal models and in humans. AB - Stroke-induced blood-brain barrier breakdown promotes complications like cerebral edema and hemorrhagic transformation, especially in association with therapeutical recanalization of occluded vessels. As arteries, capillaries and veins display distinct functional and morphological characteristics, we here investigated patterns of blood-brain barrier breakdown for each segment of the vascular tree in rodent models of embolic, permanent, and transient middle cerebral artery occlusion, added by analyses of human stroke tissue. Twenty-four hours after ischemia induction, loss of blood-brain barrier function towards FITC albumin was equally observed for arteries, capillaries, and veins in rodent brains. Noteworthy, veins showed highest ratios of leaky vessels, whereas capillaries exhibited the most and arteries the least widespread perivascular tracer extravasation. In contrast, human autoptic stroke tissue exhibited pronounced extravasations of albumin around arteries and veins, while the pericapillary immunoreactivity appeared only faint. Although electron microscopy revealed comparable alterations of the arterial and capillary endothelium throughout the applied animal models, structural loss of arterial smooth muscle cells was only observed in the translationally relevant model of embolic middle cerebral artery occlusion. In light of the so far available concepts of stroke treatment, the consideration of a differential vascular pathophysiology along the cerebral vasculature is likely to allow development of novel effective treatment strategies. PMID- 27683450 TI - Incidence, hemodynamic, and electrical characteristics of spreading depolarization in a swine model are affected by local but not by intravenous application of magnesium. AB - The aim was to characterize the effects of magnesium sulfate, using i.v. bolus and local administration, using intrinsic signal imaging, and on electrocorticographic activity during the induction and propagation of spreading depolarizations in the gyrencephalic porcine brain. Local application of magnesium sulfate led to a complete inhibition of spreading depolarizations. One hour after washing out the topical magnesium sulfate, re-incidence of the spreading depolarizations was observed in 50% of the hemispheres. Those spreading depolarizations showed attenuation in hemodynamic characteristics and speed in intrinsic optical signal imaging. The electrical amplitude decreased through electrocorticographic activity. Intravenous magnesium therapy showed no significant effects on spreading depolarization incidence and characteristics. PMID- 27683453 TI - One in five with bowel cancer diagnosed as emergency had previous "red flag" symptoms. PMID- 27683451 TI - Effects of voluntary exercise on structure and function of cortical microvasculature. AB - Aerobic activity has been shown highly beneficial to brain health, yet much uncertainty still surrounds the effects of exercise on the functioning of cerebral microvasculature. This study used two-photon fluorescence microscopy to examine cerebral hemodynamic alterations as well as accompanying geometric changes in the cortical microvascular network following five weeks of voluntary exercise in transgenic mice endogenously expressing tdTomato in vascular endothelial cells to allow visualization of microvessels irrespective of their perfusion levels. We found a diminished microvascular response to a hypercapnic challenge (10% FiCO2) in running mice when compared to that in nonrunning controls despite commensurate increases in transcutaneous CO2 tension. The flow increase to hypercapnia in runners was 70% lower than that in nonrunners (p = 0.0070) and the runners' arteriolar red blood cell speed changed by only half the amount seen in nonrunners (p = 0.0085). No changes were seen in resting hemodynamics or in the systemic physiological parameters measured. Although a few unperfused new vessels were observed on visual inspection, running did not produce significant morphological differences in the microvascular morphometric parameters, quantified following semiautomated tracking of the microvascular networks. We propose that voluntary running led to increased cortical microvascular efficiency and desensitization to CO2 elevation. PMID- 27683452 TI - Measuring vascular reactivity with resting-state blood oxygenation level dependent (BOLD) signal fluctuations: A potential alternative to the breath holding challenge? AB - Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 +/- 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R2 = 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical. PMID- 27683454 TI - An Emerging Role of TEX101 Protein as a Male Infertility Biomarker. AB - Infertility is an important aspect of human reproduction. It affects up to 15% of couples, with the male factor contributing to approximately 50% of all cases. Azoospermia is one of the most severe forms of male infertility, which is characterized by the absence of sperm in semen. The mechanisms underlying male infertility remain unknown. Currently, clinicians rely on semen analysis to predict the reproductive potential of a male, and testicular biopsy is the only reliable method to diagnose different subtypes of azoospermia. Recently, advances in proteomics encouraged the search for novel male infertility biomarkers in seminal plasma. In this review, we focus on TEX101, a testicular germ cell specific protein, one of the most promising male infertility biomarkers. We discuss its role in spermatogenesis and fertilization and summarize our current knowledge about this new potential biomarker. PMID- 27683455 TI - Genetic and Epigenetic Changes After Spermatogonial Stem Cell Culture and Transplantation. AB - Men with testicular failure, either primary or secondary, have been shown to be interested in fertility preservation. Spermatogonial stem cell (SSC) transplantation is currently being investigated as a treatment for this. Currently this experimental technique consists of cryopreservation of a testicular biopsy prior to cancer treatment, followed by optional in vitro expansion of SSCs and auto transplantation after cancer treatment. This technique may restore the pool of SSCs resulting in restoration of spermatogenesis. While this technique has not been applied to humans due to its highly experimental nature and concerns of malignant contamination, animal studies have been successful. While the offspring obtained from SSCs appear to be healthy in rodent models, there is relatively little data on any genetic and epigenetic changes that occur in either the transplanted SSCs or offspring. In humans, male germ cells undergo unique and extensive chromatin and epigenetic remodeling soon after their destiny as a spermatocyte has been secured. Errors in this remodeling may cause altered genetic information to be transmitted to offspring, resulting in abnormalities. This is particularly pertinent for cancer patients as SSCs obtained from these men may have a predisposition for genetic instability even prior to starting gonadotoxic therapies. In this article, landmarks in the evolution of SSC transplantation are reviewed, along with presently known genetic, epigenetic, and imprinting abnormalities that may occur after in vitro propagation and transplantation. PMID- 27683456 TI - Mechanisms of Androgen-Independent Prostate Cancer. AB - Prostate cancer is the second leading cause of cancer-related deaths among men in North America. Almost all prostate cancers begin in an androgen-dependent state, so androgen deprivation therapy is administered and results in improved clinical outcomes. However, over time, some cancerous cells are able to survive and grow during this treatment, resulting in androgen-independent prostate cancer. At this point, the disease is fatal, as there are no effective targeted therapies available. Most prostate cancer tumors require androgen receptor (AR) signalling for survival. During the progression to androgen-independence, this signalling cascade has been found to be altered at many levels within prostate cancers. Mechanisms that enhance AR signalling during androgen deprivation include: AR gene amplifications, AR gene mutations, changes in expression of AR co-regulatory proteins, changes in expression of steroid-generating enzymes, ligand-independent activation of AR via 'outlaw' pathways, and AR-independent pathways that become activated, termed 'bypass' pathways. One or more of these aforementioned changes can lead to prostate cancer cells to gain androgen-independent properties. Understanding the molecular alterations that occur during this process will allow for improved therapeutic strategies to target key molecules and pathways important for this progression. PMID- 27683457 TI - Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa). AB - PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of (~)50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID- 27683458 TI - miRNA in Prostate Cancer: New Prospects for Old Challenges. AB - Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men but has limited prognostic biomarkers available for follow up. MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression of their target genes. Accumulating experimental evidence reports differential miRNA expression in PCa, and that miRNAs are actively involved in the pathogenesis and progression of PCa. miRNA and androgen receptor signaling cross-talk is an established factor in PCa pathogenesis. Differential miRNA expression was found between patients with high versus low Gleason scores, and was also observed in patients with biochemical failure, hormone-resistant cancer and in metastasis. Metastasis requires epithelial-mesenchymal transition which shares many cancer stem cell biological characteristics and both are associated with miRNA dysregulation. In the era of personalized medicine, there is a broad spectrum of potential clinical applications of miRNAs. These applications can significantly improve PCa management including their use as diagnostic and/or prognostic markers, or as predictive markers for treatment efficiency. Preliminary evidence demonstrates that miRNAs can also be used for risk stratification. Circulatory miRNAs can serve as non-invasive biomarkers in urine and/or serum of PCa patients. More recently, analysis of miRNAs and circulating tumor cells are gaining significant attention. Moreover, miRNAs represent an attractive new class of therapeutic targets for PCa. Here, we summarize the current knowledge and the future prospects of miRNAs in PCa, their advantages, and potential challenges as tissue and circulating biomarkers. Prostate cancer (PCa) is the most commonly diagnosed cancer among men in western populations. The American Cancer Society estimated 239, 590 new cases and 29, 720 expected deaths in the USA in 2013. One in every six men are at risk of developing PCa during their lifetime (1). Currently, the standard biomarker for PCa diagnosis is prostate-specific antigen (PSA), which has its limitations, leading to the risks of PCa over diagnosis and harmful overtreatment. The prognostic value of PSA is also questionable (2). Stepping into the new epoch of personalized medicine, molecular markers are urgently needed to improve the different aspects of PCa management (3). miRNAs represent an attractive class of emerging biomarkers that can help in this regard (4;5). PMID- 27683460 TI - Estimation of Alert and Change Limits of Haematological Quantities and its Application in the Plausibility Control. AB - INTRODUCTION: In the process of quality assurance of the measured values of the clinical laboratory, one of the purposes is to perform the validation of patients' measured values in the most objective way. This validation process is called plausibility control which may be defined as the set of procedures used to decide if a patient's measured value is valid according to established clinical and biological criteria. The aim of this study is to propose a model to estimate alert and change limits of measured values of the blood cell count, to be applied to detect doubtful patients' measured values. METHODS: Some alert and change limits were estimated from the emergency laboratory database of the year 2010 using different percentiles. A verification of the suitability of the proposed model was also performed. RESULTS: Most of the fractions of the measured values excluded by the alert and change limits were according to the theoretical expected. The overall fraction of the number of doubtful clinical laboratory reports ranged between 0.6 and 47.6 %. CONCLUSIONS: The proposed model helps, improves and standardizes the process of detection of doubtful measured values since they are produced objectively. These limits can also be configured in a laboratory information system letting the clinical laboratory professional staff to save time and efforts. PMID- 27683462 TI - Risk Management for Point-of-Care Testing. AB - Point-of-care testing (POCT) is growing in popularity, and with this growth comes an increased chance of errors. Risk management is a way to reduce errors. Originally developed for the manufacturing industry, risk management principles have application for improving the quality of test results in the clinical laboratory. The Clinical and Laboratory Standards Institute (CLSI), EP23-A Laboratory Quality Control based on Risk Management guideline, introduces risk management to the clinical laboratory and describes how to build and implement a quality control plan for a laboratory test. A simple, unit-use blood gas analyzer is utilized as an example for developing a laboratory quality control plan. The US Centers for Medicare and Medicaid Services (CMS) has revised the Clinical and Laboratory Improvement Amendments (CLIA) interpretive guidelines to provide a new quality control option, individualized quality control plans (IQCP), for decreasing the frequency of analyzing liquid controls from two levels each day of testing to manufacturer recommended frequencies in conjunction with a device's built-in internal control processes and the risk of error when testing with that device. IQCPs have the advantage of allowing laboratories the flexibility to adopt alternative control processes in concert with traditional liquid controls to improve efficiency and cost effectiveness while providing optimal quality POCT results for patient care. PMID- 27683463 TI - Virtual Support of a Point of Care Testing Network. PMID- 27683459 TI - Urothelial Bladder Cancer Urinary Biomarkers. AB - Urothelial bladder cancer is the fourth most prevalent male malignancy in the United States and also one of the ten most lethal. Superficial or non-muscle invasive bladder cancer has a high rate of recurrence and can progress to muscle invasive disease. Conventional surveillance requires regular cystoscopy and is used often with urinary cytology. Unfortunately, the cystoscopy procedure is invasive for patients and costly for health care providers. Urinary biomarkers have the potential to improve bladder cancer diagnosis, the efficiency and also the cost-effectiveness of follow up. It may also be possible for urinary biomarkers to help prognosticate particularly for patients with high-grade bladder cancer who may want enhanced assessment of their risk of disease progression. In this review the important historical urinary biomarkers and the newly emerging biomarkers are discussed. As will be presented, although many of the tests have good performance characteristics, unfortunately no single test can fulfill all the roles currently provided by cystoscopy and cytology. It is likely that in the future, urinary biomarker testing will be used selectively in a personalized manner to try and improve prognostication or reduce the necessity for invasive cystoscopy in patients understanding the limits of the test. PMID- 27683461 TI - Principles of Point of Care Culture, the Spatial Care PathTM, and Enabling Community and Global Resilience: Enabling Community and Global Resilience. AB - GOALS: This article a) defines point of care (POC) culture; b) presents seven underlying fundamental principles; c) describes the importance of needs assessment; d) introduces a new innovation, the spatial care pathTM; and e) illustrates how POC testing that properly fulfills needs and spatial care pathsTM enable community and global resilience. OBSERVATIONS: Often, POC testing supplants the conventional clinical laboratory, which may be too distant, prohibitively expensive, or simply not available in limited-resource settings. New POC technologies "fit" future medical problem solving. Screening and testing directly in the home or primary care facilitate rapid diagnosis, monitoring, and treatment. In contrast to the past where attention has been placed on emergency departments, hospitals, and referral centers, the spatial care pathTM starts with the patient and guides him or her through an efficient strategy of care in small world networks (SWNs) defined by local geography and topology, long-standing customs, public health jurisdictions, and geographic information systems (GIS). CONCLUSIONS: POC testing needs in limited-resource settings are striking. Fulfillment is best guided by thorough understanding of POC culture. Quick feedback and fast decision-making by patients and physicians alike yield significant value that motivates changes in patient lifestyles and physician interactions. Culturally sensitive technology assimilation addresses leadership challenges in nations adapting to increasing populations of young and old, despite scarcity of resources. The spatial care pathTM facilitates an essential balance of prevention and intervention in public health and shifts future focus to the patient, empowerment, and primary care within the context of POC culture. PMID- 27683464 TI - Recent Advances in Point-of-Care Diagnostics for Cardiac Markers. AB - National and international cardiology guidelines have recommended a 1-hour turnaround time for reporting results of cardiac troponin to emergency department personnel, measured from the time of blood collection to reporting. Use of point of-care testing (POCT) can reduce turnaround times for cardiac markers, but current devices are not as precise or sensitive as central laboratory assays. The gap is growing as manufacturers of mainframe immunoassay instruments have or will release troponin assays that are even higher than those currently available. These assays have analytical sensitivity that enables detection of nearly 100% of all healthy subjects which is not possible for current POCT assays. Use of high sensitivity troponin results in a lower value for the 99(th) percentile of a healthy population. Clinically, this enables for the detection of more cases of myocardial injury. In order to compete analytically, next generation POCT assays will to make technologic advancements, such as the use of microfluidic to better control sample delivery, nanoparticles or nanotubes to increase the surface-to volume ratios for analytes and antibodies, and novel detection schemes such as chemiluminescence and electrochemical detectors to enhance analytical sensitivity. Multi-marker analysis using POCT is also on the horizon for tests that complement cardiac troponin. PMID- 27683465 TI - Glucose Meter Use in the Intensive Care Unit: Much Ado About Something. AB - Glucose meters are a fast and convenient way to measure circulating blood glucose. Like many technologies in healthcare, the use of glucose meters within the hospital has evolved significantly over the last few decades. This change has been driven predominantly by changes in the approach to glycemic control for critically ill patients. Both glycemic control in the intensive care unit (ICU), and use of glucose meters to manage insulin dosing during glycemic control, are likely to remain controversial topics in the years to come. This review will elaborate on the evidence for and against use of glucose meters in the ICU to monitor glucose concentrations during glycemic control, and provide some tips for point of care programs on how to evaluate glucose monitors for this purpose. PMID- 27683466 TI - Infection Transmission Associated with Point of Care Testing and the Laboratory's Role in Risk Reduction. AB - Lack of knowledge and confusion exists regarding safe and appropriate use of blood glucose monitoring equipment. Increasing numbers of diabetics, and exponential growth in blood glucose monitoring presents increased opportunities for infection transmission between patients. Diabetics have increased exposure to blood and blood borne pathogens from frequent blood glucose monitoring. Risk factors have been identified in infectious outbreaks and by analysis of testing practice. Point of care blood glucose meters are frequently contaminated by blood. Bacterial and viral organisms survive on surfaces and in dried blood. Instrumentation is shared between patients, and is heavily utilized in institutional settings, so that serial testing is performed on multiple patients within a short timeframe. Hand hygiene, glove changes and meter disinfection between testing events has been found to be inconsistent. Time pressure for meter usage competes with proper cleaning and disinfection procedures. Meter storage areas are frequently contaminated by blood. Multi-use lancets, improperly used for serial patient blood sampling, are a source for infection transmission. Test strips in vials, frequently contaminated by bacterial organisms, present potential hazard. The responsibility of the clinical laboratory is to insure successful implementation of practices that insure patient safety. Risk reduction strategies include single-use auto-disabling skin puncture devices for blood sampling; hand hygiene and glove change for every testing event; effective meter cleaning and disinfection for every testing event; meter use restriction to a single patient; safe practices for glucose meter storage; infection control practices to reduce contamination of blood glucose test strips or changes in test strip packaging and test strip dispensing. PMID- 27683467 TI - Primary Hypoparathyroidism Misdiagnosed as Epilepsy - A Case Report: Seizures, hypocalcemia and cerebral calcification. AB - Absent or inappropriately low intact parathyroid hormone along with hypocalcemia is the diagnostic criterion of hypoparathyroidism. Clinically, hypoparathyroidism manifests predominantly as neuromuscular dysfunction caused by hypocalcemia. We present here a case of hypoparathyroidism wrongly and ineffectively treated as epilepsy for four years prior to reporting to our hospital. Hypoparathyroidism was diagnosed in our patient on the basis of low serum calcium (ionized and total), high phosphate and very low IPTH levels in face of normal magnesium levels along with radiological evidence of cerebral calcification. The authors stress on the need to include hypoparathyroidism in the differential diagnosis of seizures and the need to treat with 1, 25 dihydroxycholecalciferol. PMID- 27683468 TI - Polish Code of Ethics of a Medical Laboratory Specialist. AB - Along with the development of medicine, increasingly significant role has been played by the laboratory diagnostics. For over ten years the profession of the medical laboratory specialist has been regarded in Poland as the autonomous medical profession and has enjoyed a status of one of public trust. The process of education of medical laboratory specialists consists of a five-year degree in laboratory medicine, offered at Medical Universities, and of a five-year Vocational Specialization in one of the fields of laboratory medicine such as clinical biochemistry, medical microbiology, medical laboratory toxicology, medical laboratory cytomorphology and medical laboratory transfusiology. An important component of medical laboratory specialists' identity is awareness of inherited ethos obtained from bygone generations of workers in this particular profession and the need to continue its further development. An expression of this awareness is among others Polish Code of Ethics of a Medical Laboratory Specialist (CEMLS) containing a set of values and a moral standpoint characteristic of this type of professional environment. Presenting the ethos of the medical laboratory specialist is a purpose of this article. Authors focus on the role CEMLS plays in areas of professional ethics and law. Next, they reconstruct the Polish model of ethos of medical diagnostic laboratory personnel. An overall picture consists of a presentation of the general moral principles concerning execution of this profession and rules of conduct in relations with the patient, own professional environment and the rest of the society. Polish model of ethical conduct, which is rooted in Hippocratic medical tradition, harmonizes with the ethos of medical laboratory specialists of other European countries and the world. PMID- 27683470 TI - Peer Review in Scientific Publications: Benefits, Critiques, & A Survival Guide. AB - Peer review has been defined as a process of subjecting an author's scholarly work, research or ideas to the scrutiny of others who are experts in the same field. It functions to encourage authors to meet the accepted high standards of their discipline and to control the dissemination of research data to ensure that unwarranted claims, unacceptable interpretations or personal views are not published without prior expert review. Despite its wide-spread use by most journals, the peer review process has also been widely criticised due to the slowness of the process to publish new findings and due to perceived bias by the editors and/or reviewers. Within the scientific community, peer review has become an essential component of the academic writing process. It helps ensure that papers published in scientific journals answer meaningful research questions and draw accurate conclusions based on professionally executed experimentation. Submission of low quality manuscripts has become increasingly prevalent, and peer review acts as a filter to prevent this work from reaching the scientific community. The major advantage of a peer review process is that peer-reviewed articles provide a trusted form of scientific communication. Since scientific knowledge is cumulative and builds on itself, this trust is particularly important. Despite the positive impacts of peer review, critics argue that the peer review process stifles innovation in experimentation, and acts as a poor screen against plagiarism. Despite its downfalls, there has not yet been a foolproof system developed to take the place of peer review, however, researchers have been looking into electronic means of improving the peer review process. Unfortunately, the recent explosion in online only/electronic journals has led to mass publication of a large number of scientific articles with little or no peer review. This poses significant risk to advances in scientific knowledge and its future potential. The current article summarizes the peer review process, highlights the pros and cons associated with different types of peer review, and describes new methods for improving peer review. PMID- 27683471 TI - Ethics in Online Publications. AB - Journals have been publishing the results of scientific investigations since the founding of Philosophical Transactions in 1665. Since then we have witnessed a massive expansion in the number of journals to the point that there are now approximately 28,000 active, peer reviewed journals collectively publishing more than 1.8 million articles per year. Before the mid-1990s, these journals were only available on paper but by the end of the 20th century, most journals had moved to online platforms. Online publication has also served as the impetus for the move to 'open-access' to the information contained in journals. The fact that a publication is 'on-line' and 'open-access' does not negate the responsibility of the author and the publisher to publish in an ethical way. [1] The document produced by the IFCC Ethics Task Force (TF-E) on publication ethics states that 'Ethics in Science at its broadest level encompasses research ethics, medical ethics, publication ethics, conflicts of interest, ethical responsibilities as educator, plus many other areas.' Thus publication ethics is a continuum from the first step of research design through to the information being read by the reader. In general terms 'publication ethics' includes the ethical behaviour of the authors in writing and submitting a scientific manuscript to a publisher for the purpose of publication, thus any discussion of publication ethics must include the role of the authors, referees, publisher and reader and the issues of authorship (and the use of 'ghosts'), plagiarism, duplicate publication (including in different languages), image manipulation (particularly in the era of digitisation), and conflict of interest [2]. To aid the authors, and others involved in the process of publication, a number of resources are now available particularly those from the Committee on Publication Ethics (COPE) [3] and the World Association of Medical Editors (WAME) [4]. More recently the issue of 'publisher ethics' has also been raised, particularly with the sudden increase of what could be termed 'predatory' publishers utilising the open access model to publish low quality articles, which often do not adhere to the guidelines mentioned above, utilising an author-pays model of open-access publishing for their own profit [5]. PMID- 27683469 TI - KLK-targeted Therapies for Prostate Cancer. AB - Alternative treatments are urgently needed for prostate cancer, especially to address the aggressive metastatic castration-resistant disease. Proteolytic enzymes are involved in cancer growth and progression. The prostate produces several proteases, the most abundant ones being two members of the kallikrein related peptidase (KLK) family, prostate-specific antigen (PSA) and KLK2. Despite the wide use of PSA as a clinical marker, the function(s) of PSA and other KLKs in prostate cancer are poorly known. Hypothetic roles of KLKs in prostate cancer include activities that may both promote and inhibit cancer growth and metastasis, including the antiangiogenic activity of PSA. Thus it may be possible to control prostate cancer growth by modulating the proteolytic activities of KLKs. PSA and KLK2 are especially attractive targets for prostate cancer treatment because of their proposed roles in tumor development and inhibition of angiogenesis in combination with their prostate selective expression. So far the number of molecules affecting selectively the activity of KLKs is limited and none of these are used to treat prostate cancer. Prodrugs that, after cleavage of the peptide part by PSA or KLK2, release active drug molecules, and PSA-targeted therapeutic vaccines have already been tested clinically in humans and the first results have been encouraging. Although KLKs are attractive targets for prostate cancer treatment, much remains to be done before their potential can be fully elucidated. The objective of this review is to address the current state of the KLKs as novel therapeutic targets for prostate cancer treatment. PMID- 27683472 TI - Open Access Publishing in the Electronic Age. AB - The principle of open-access (OA) publishing is more and more prevalent also on the field of laboratory medicine. Open-access journals (OAJs) are available online to the reader usually without financial, legal, or technical barriers. Some are subsidized, and some require payment on behalf of the author. OAJs are one of the two general methods for providing OA. The other one is self-archiving in a repository. The electronic journal of the IFCC (eJIFCC) is a platinum OAJ- i.e. there is no charge to read, or to submit to this journal. Traditionally, the author was required to transfer the copyright to the journal publisher. Publishers claimed this was necessary in order to protect author's rights. However, many authors found this unsatisfactory, and have used their influence to affect a gradual move towards a license to publish instead. Under such a system, the publisher has permission to edit, print, and distribute the article commercially, but the author(s) retain the other rights themselves. An OA mandate is a policy adopted by a research institution, research funder, or government which requires researchers to make their published, peer-reviewed journal articles and conference papers OA by self-archiving their peer-reviewed drafts in a repository ("green OA") or by publishing them in an OAJ ("gold OA"). Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. The free, easy-to-use copyright licenses provide a simple, standardized way to give the public permission to share and use creative work. CC licenses let you easily change your copyright terms from the default of "all rights reserved" to "some rights reserved." OA publishing also raises a number of new ethical problems (e.g. predatory publishers, fake papers). Laboratory scientists are encouraged to publish their scientific results OA (especially in eJIFCC). They should, however, be aware of their rights, institutional mandate, the procedures of publishing and post-printing, and the potential risks of OAP. Recent research shows that OA articles are wider seen, and are just starting to be better cited than equivalent papers published in traditional subscription journals. PMID- 27683473 TI - How to Write a Scientific Paper: Practical Guidelines. AB - Precise, accurate and clear writing is essential for communicating in health sciences, as publication is an important component in the university criteria for academic promotion and in obtaining funding to support research. In spite of this, the development of writing skills is a subject infrequently included in the curricula of faculties of medicine and allied health sciences. Therefore clinical investigators require tools to fill this gap. The present paper presents a brief historical background to medical publication and practical guidelines for writing scientific papers for acceptance in good journals. PMID- 27683474 TI - Kallikrein-Related Peptidases in Prostate Cancer: From Molecular Function to Clinical Application. AB - Prostate cancer is a leading contributor to male cancer-related deaths worldwide. Kallikrein-related peptidases (KLKs) are serine proteases that exhibit deregulated expression in prostate cancer, with KLK3, or prostate specific antigen (PSA), being the widely-employed clinical biomarker for prostate cancer. Other KLKs, such as KLK2, show promise as prostate cancer biomarkers and, additionally, their altered expression has been utilised for the design of KLK targeted therapies. There is also a large body of in vitro and in vivo evidence supporting their role in cancer-related processes. Here, we review the literature on studies to date investigating the potential of other KLKs, in addition to PSA, as biomarkers and in therapeutic options, as well as their current known functional roles in cancer progression. Increased knowledge of these KLK-mediated functions, including degradation of the extracellular matrix, local invasion, cancer cell proliferation, interactions with fibroblasts, angiogenesis, migration, bone metastasis and tumour growth in vivo, may help define new roles as prognostic biomarkers and novel therapeutic targets for this cancer. PMID- 27683475 TI - Estimating the need for palliative care at the population level: A cross-national study in 12 countries. AB - BACKGROUND: To implement the appropriate services and develop adequate interventions, detailed estimates of the needs for palliative care in the population are needed. AIM: To estimate the proportion of decedents potentially in need of palliative care across 12 European and non-European countries. DESIGN: This is a cross-sectional study using death certificate data. SETTING/PARTICIPANTS: All adults (?18 years) who died in 2008 in Belgium, Czech Republic, France, Hungary, Italy, Spain (Andalusia, 2010), Sweden, Canada, the United States (2007), Korea, Mexico, and New Zealand ( N = 4,908,114). Underlying causes of death were used to apply three estimation methods developed by Rosenwax et al., the French National Observatory on End-of-Life Care, and Murtagh et al., respectively. RESULTS: The proportion of individuals who died from diseases that indicate palliative care needs at the end of life ranged from 38% to 74%. We found important cross-country variation: the population potentially in need of palliative care was lower in Mexico (24%-58%) than in the United States (41%-76%) and varied from 31%-83% in Hungary to 42%-79% in Spain. Irrespective of the estimation methods, female sex and higher age were independently associated with the likelihood of being in need of palliative care near the end of life. Home and nursing home were the two places of deaths with the highest prevalence of palliative care needs. CONCLUSION: These estimations of the size of the population potentially in need of palliative care provide robust indications of the challenge countries are facing if they want to seriously address palliative care needs at the population level. PMID- 27683476 TI - Palliative care for Parkinson's disease: Patient and carer's perspectives explored through qualitative interview. AB - BACKGROUND: Palliative care is recommended for non-malignant illnesses, including Parkinson's disease. However, past research with healthcare workers highlights unmet palliative needs in this population and referral rates to Specialist Palliative Care are low. Some healthcare workers perceive a 'fear' in their patients about introducing palliative care. However, less is known about the views of people with Parkinson's disease and their carers about palliative care. AIM: (1) To explore the palliative care and related issues most affecting people with Parkinson's disease and their families and (2) to examine perceptions about/understanding of palliative care. DESIGN: This was a qualitative study; semi-structured interviews were conducted, transcribed and analysed using thematic analysis. SETTING/PARTICIPANTS: A total of 31 people participated, both people with Parkinson's disease ( n = 19) and carers ( n = 12), across three Movement Disorder Clinics in the Republic of Ireland. RESULTS: People with Parkinson's disease and their carers were unfamiliar with the term palliative care. When informed of the role of palliative care, most felt that they would benefit from this input. People with Parkinson's disease and carers experienced a high illness burden and wanted extra support. Crises requiring Specialist Palliative Care involvement may occur at diagnosis and later, with advancing illness. Participants wanted more information about palliative care and especially further supports to address their psychosocial needs. CONCLUSION: A holistic palliative care approach could address the complex physical and psychosocial symptoms experienced by people with Parkinson's disease and their carers, and people with Parkinson's disease and their carers are open to palliative care. Further research needs to explore how palliative care can be introduced into the routine care for people with Parkinson's disease. PMID- 27683477 TI - Diagnostic Errors and Laboratory Medicine - Causes and Strategies. AB - While the frequency of laboratory errors varies greatly, depending on the study design and steps of the total testing process (TTP) investigated, a series of papers published in the last two decades drew the attention of laboratory professionals to the pre- and post-analytical phases, which currently appear to be more vulnerable to errors than the analytical phase. In particular, a high frequency of errors and risk of errors that could harm patients has been described in both the pre-pre- and post-post-analytical steps of the cycle that usually are not under the laboratory control. In 2008, the release of a Technical Specification (ISO/TS 22367) by the International Organization for Standardization played a key role in collecting the evidence and changing the perspective on laboratory errors, emphasizing the need for a patient-centred approach to errors in laboratory testing. PMID- 27683478 TI - Towards Better Test Utilization - Strategies to Improve Physician Ordering and Their Impact on Patient Outcomes. AB - Laboratory medicine is the single highest volume medical activity in healthcare and demand for laboratory testing is increasing disproportionately to medical activity. It has been estimated that $6.8 billion of medical care in the US involves unnecessary testing and procedures that do not improve patient care and may even harm the patient. Physicians face many challenges in accurately, efficiently and safely ordering and interpreting diagnostic tests. In order to improve patient outcomes, laboratory tests must be appropriately ordered, properly conducted, reported in a timely manner, correctly interpreted and affect a decision for future diagnosis and treatment of the patient. PMID- 27683479 TI - Collaborating with International Clinical Organizations. AB - The provision of quality laboratory services for patient care to improve healthcare outcomes is at the centre of the work of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). However the day to day work of laboratory medicine practitioners largely does not involve direct contact with patients. The IFCC Executive Board has therefore included in its strategic plan activities to highlight collaboration with clinical organizations. PMID- 27683480 TI - The Impact for Patient Outcomes of Failure to Follow Up on Test Results. How Can We Do Better? AB - BACKGROUND: The World Health Organization-World Alliance for Patient Safety has identified test result management as a priority area. Poor test result follow-up can have major consequences for the quality of care, including missed diagnoses and suboptimal patient outcomes. Over the last three decades there has been considerable growth in the number of requests for pathology and radiology services which has added to the complexity of how patient care is delivered and test results are managed. This can contribute to a lack of clarity about where and with whom responsibility for test follow-up should reside: a problem that is compounded by a lack of clear definitions about what are critical, unexpected or significantly abnormal results. AIM OF THIS PAPER: This paper will present a narrative review highlighting key issues related to the problem of failure to follow up laboratory test results, and outline potential solutions. CONCLUSIONS: Information technology (IT) has the potential to enhance the performance and safety of test result management processes. Effective solutions must engage all stakeholders, including consumers, in arriving at decisions about who needs to receive results, how and when they are communicated, and how they are acknowledged and acted upon and the documentation of these actions. PMID- 27683482 TI - Evaluating Biomarkers for Guiding Treatment Decisions. AB - The genetic revolution is expected to lead to improved targeting of new and existing forms of treatment. Rather than a one-size-fits-all blockbuster strategy in battling disease with drugs and other interventions, a more precise approach is becoming available, one in which treatment is only offered to those likely to benefit. The identification of those likely to benefit from treatment could be based on one or more biomarkers, but in an era where medical decisions aim to be evidence-based, the use of treatment selection markers should not just be based on hope and optimism, but on solid data from sound research. The performance of the treatment selection marker should be expressed in quantitative terms, similar to the way we express the clinical performance of diagnostic markers, or the performance of prognostic markers. PMID- 27683481 TI - The Clinical and Health Economic Value of Clinical Laboratory Diagnostics. AB - The ultimate goal of diagnostic testing is to guide disease management in order to improve patient outcomes and patient well-being. Patient populations are rarely homogenous and accurate diagnostic tests can dissect the patient population and identify those patients with similar symptoms but very different underlying pathophysiology that will respond differently to different treatments. This stratification of patients can direct patients to appropriate treatment and is likely to result in clinical benefits for patients and economic benefits for the healthcare system. In this article we look at the clinical and economic benefits afforded by clinical laboratory diagnostics in three disease areas that represent substantial clinical and healthcare burdens to society; heart failure, Alzheimer's disease and asthma. PMID- 27683483 TI - Clinical Characterization, Genetics, and Long-Term Follow-up of a Large Cohort of Patients With Agenesis of the Corpus Callosum. AB - To gain a better understanding of the clinical and genetic features associated with agenesis of corpus callosum, we enrolled and characterized 162 patients with complete or partial agenesis of corpus callosum. Clinical and genetic protocols allowed us to categorize patients as syndromic subjects, affected by complex extra-brain malformations, and nonsyndromic subjects without any additional anomalies. We observed slight differences in sex ratio (56% males) and agenesis type (52% complete). Syndromic agenesis of corpus callosum subjects were prevalent (69%). We detected associated cerebral malformations in 48% of patients. Neuromotor impairment, cognitive and language disorders, and epilepsy were frequently present, regardless of the agenesis of corpus callosum subtype. Long-term follow-up allowed us to define additional indicators: syndromic agenesis of corpus callosum plus patients showed the most severe clinical features while isolated complete agenesis of corpus callosum patients had the mildest symptoms, although we observed intellectual disability (64%) and epilepsy (15%) in both categories. We achieved a definitive (clinical and/or genetic) diagnosis in 42% of subjects. PMID- 27683486 TI - Testosterone Deficiency - Establishing A Biochemical Diagnosis. AB - Testosterone deficiency is a common and often unrecognized disorder impacting the lives of many men. Symptoms related to low testosterone are relatively non specific and clinicians must therefore ensure that a patients' symptomatology is supported by a biochemical profile suggestive of testosterone deficiency. There are many options available to determine a patient's testosterone level and laboratories will vary in the type of biochemical assessment they provide. In assessing patients with suspected low testosterone, the presence of symptoms and a low total testosterone is usually sufficient to initiate therapy. In equivocal cases, measurement of free or bioavailable testosterone with a reliable assay can further clarify the clinical picture. By understanding the differences between total, free and bioavailable testosterone, and the accuracy and reliability of their measurement, clinicians can better interpret their patients' biochemical testosterone profile. PMID- 27683484 TI - Prostate Cancer Genetics: A Review. AB - Over the past decades, research has focussed on identifying the genetic underpinnings of prostate cancer. It has been recognized that a number of forms of genetic changes coupled with epigenetic and gene expression changes can increase the prediction to develop prostate cancer. This review outlines the role of somatic copy number alterations (SCNAs), structural rearrangements, point mutations, and single nucleotide polymorphisms (SNPs) as well as miRNAs. Identifying relevant genetic changes offers the ability to develop novel biomarkers to allow early and accurate detection of prostate cancer as well as provide risk stratification of patients following their diagnosis. The concept of personalized or individualized medicine has gained significant attention. Therefore, a better understanding of the genetic and metabolic pathways underlying prostate cancer development offers the opportunity to explore new therapeutic interventions with the possibility of offering patient-specific targeted therapy. PMID- 27683485 TI - Metabolomics and its Application to the Development of Clinical Laboratory Tests for Prostate Cancer. AB - INTRODUCTION: There is a critical need to develop clinical laboratory assays that provide risk assessment for men at elevated risk for prostate cancer, and once diagnosed, could further identify those men with clinically significant disease. METHODS: Recent advancements in analytical instrumentation have enabled mass spectrometry-based metabolomics methodologies. Further advancements in chromatographic techniques have facilitated high throughput, quantitative assays for a broad spectrum of biochemicals. RESULTS: Screening metabolomics techniques have been applied to biospecimens from large cohorts of men comparing those individuals with prostate cancer to those with no evidence of malignancy. Work beginning in tissues has identified biochemical profiles that correlate with disease and disease severity, including tumor grade and stage. Some of these metabolic abnormalities, such as dramatic elevations in sarcosine, have been found to translate into biological fluids, especially blood and urine, which can be sampled in a minimally invasive manner. DISCUSSION: The differential abundances of these tumor-associated metabolites have been found to improve the performance of clinical prognostic/diagnostic tools. CONCLUSION: The outlook is bright for metabolomic technology to address clinical diagnostic needs for prostate cancer patient management. Early validation of specific clinical tests provides a preview of further successes in this area. Metabolomics has shown its utility to complement and augment traditional clinical approaches as well as emerging genomic, transcriptomic and proteomic methodologies, and is expected to play a key role in the precision medicine-based management of the prostate cancer patient. PMID- 27683488 TI - Organization of the POCT Unit. AB - Point-of-care testing (POCT) has evolved as an important part of laboratory medicine by virtue of its compactness, portability, and the feasibility of operation by nonlaboratory personnel, where fast and accurate testing methods are a primary concern and, as a result, improving the patient care. To successfully achieve POCT quality in networks, a multidisciplinary organizational approach is required. A clearly defined organizational structure should be put in place for proper functioning and optimum utilization of each POCT unit. The POCT unit must include designated authority, responsibility, and accountability. PMID- 27683489 TI - Physical activity programme reduces major disability in elderly people, study shows. PMID- 27683487 TI - Clinical Relevance of Trace Bands on Serum Electrophoresis in Patients Without a History of Gammopathy. AB - Serum protein electrophoresis (SPE) and immunofixation is commonly used to screen for plasma cell dyscrasias. Interpretation of these tests is qualitative by nature and can yield trace, faint, or scarcely visible immunoglobulin bands (TFS), which can be difficult to classify. Whether these bands should be reported at all is challenging given their unknown clinical significance. In the present study, we retrospectively analyzed 14,036 physician-ordered protein SPE and immunofixation electrophoresis (IFE) tests on serum and urine specimens (from 4,091 patients) during the period of 2000-2010. We found that 17% of all IFE results evaluated for the presence of monoclonal gammopathies (2,389 out of 14,036) contained TFS bands, representing 4.2% (173 out of 4091) of all patients evaluated. Sixty of these patients (42%) had no previous history of gammopathy, and were clinically evaluated over a mean period of up to five years from the original diagnosis of plasma cell pathology. None of these patients had progressed to multiple myeloma, lymphoplasmacytic lymphoma, plasmacytoma, or leukemia. The remaining 82 patients (58%) had a previous history of gammopathy, but had not progressed to any symptomatic plasma cell dyscrasia. Evaluation of these patients was followed for a median period of 4.3 years, with a mean of 21.5 IFE tests per individual. These data suggest that for patients without a previous history of gammopathy, the presence of TFS bands on serum protein electrophoresis does not warrant frequent follow up investigation as commonly practiced. Routine follow up of patients with a prior history of gammopathy, conversely, are warranted and may contribute to overall survival with multiple treatment options now available. For those interpreting IFE results, it may be worth considering these data when composing comments regarding suggested repeat testing frequency by SPE/IFE or alternate test methods. PMID- 27683490 TI - Are Guidelines Guiding us on How to Utilize Laboratory Tests? AB - Increasing patient risks and costs associated with the delivery of health care services have been related to inappropriate and uncontrolled use of biomarkers which make evidence-based guideline recommendations for best practice increasingly important. The translation of basic scientific discoveries into clinically meaningful studies and then to evidence-based clinical practice guidelines (CPGs) or health policy is, however, not straightforward. CPGs are potentially the most influential publications as they aim to guide clinical decisions and impact patient outcomes; hence, current approaches to their development often fail scientific publication standards. Critical appraisal of CPGs has revealed that many do not involve laboratory professionals in formulating recommendations on the use of tests; the composition of the panel could influence the scope of guidelines and over-represent certain stakeholders' views; numerous CPGs do not have rigorous evidence-based methodology and miss essential information important for the correct interpretation and application of laboratory results. PMID- 27683491 TI - Defining the Path Forward: Guidance for Laboratory Medicine Guidelines. AB - The National Academy of Clinical Biochemistry (NACB) has developed consensus based guidelines for the laboratory evaluation and monitoring of patients with specified disorders for two decades. In 1997, the NACB recognized the need to standardize the process of guideline development and promulgated its first Standard Operating Procedure (SOP) for this purpose. In 2010, the American Association of Clinical Chemistry (AACC) and NACB created the Evidence-Based Laboratory Medicine Committee (EBLMC). Among other roles, this group was given responsibility to provide oversight of clinical practice guideline development in accordance with SOP guidance and using currently accepted good practices. In 2011, the U.S. Institute of Medicine (IOM) published two reports of relevance: 'Clinical Practice Guidelines We Can Trust' and 'Finding What Works in Health Care - Standards for Systematic Reviews.' These reports were created as part of a response to a legislative mandate from the U.S. Congress requesting that steps be taken to implement recommendations from lOM's report on 'Knowing What Works in Health Care' (2008). The latest revision of the laboratory medicine practice guidelines (LMPG) SOP was in part driven by these reports. NACB continues to develop LMPGs at a rate of roughly one per year through standard processes detailed in its 2014 revision of the SOP. This article describes the NACB and EBLMC experience in developing LMPGs with a focus on the evolution and use of the latest SOP. AACC and NACB have established a solid track record in collaboratively working with many clinical societies and professional organizations on clinical practice guideline development. Presently, three LMPG's are in various stages of development and all with the collaboration of other clinical/professional groups. The practices and tools being used for current LMPGs in progress are also highlighted in the context of the challenges that presently exist for effective clinical practice guideline development in the U.S. PMID- 27683492 TI - Grading Evidence for Laboratory Test Studies Beyond Diagnostic Accuracy: Application to Prognostic Testing. AB - BACKGROUND: Evidence-based guideline development requires transparent methodology for gathering, synthesizing and grading the quality and strength of evidence behind recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) project has addressed diagnostic test use in many of their publications. Most of the work has been directed at diagnostic tests and no consensus has been reached for prognostic biomarkers. AIM OF THIS PAPER: The GRADE system for rating the quality of evidence and the strength of a recommendation is described. The application of GRADE to diagnostic testing is discussed and a description of application to prognostic testing is detailed. Some strengths and limitations of the GRADE process in relation to clinical laboratory testing are presented. CONCLUSIONS: The GRADE system is applicable to clinical laboratory testing and if correctly applied should improve the reporting of recommendations for clinical laboratory tests by standardising the style of recommendation and by encouraging transparent reporting of the actual guideline process. PMID- 27683493 TI - Evidence and Cost Effectiveness Requirements for Recommending New Biomarkers. PMID- 27683495 TI - Quality Management Systems in the Clinical Laboratories in Latin America. AB - The implementation of management systems in accordance with standards like ISO 9001:2008 (1,2) in the clinical laboratories has conferred and added value of reliability and therefore a very significant input to patient safety. As we know the ISO 9001:2008 (1) a certification standard, and ISO 15189:2012 (2) an accreditation standard, both, at the time have generated institutional memory where they have been implemented, the transformation of culture focused on correct execution, control and following, evidence needed and the importance of register. PMID- 27683494 TI - How Useful are Laboratory Practice Guidelines? AB - Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists are involved, CPGs can provide practical information which supports local laboratories as well as clinicians in the implementation and appropriate use of recommendations. Implementation of CPGs is an often neglected area that needs attention and thought. There are many barriers to successful implementation, which may vary at local level. These need to be identified early if CPGs are to be successfully adhered to. The effectiveness of CPGs also needs to be audited using process and health outcome indicators. Clinical audit is an effective tool for assessing adherence to recommendations and for measuring the impact and success of the CPG. PMID- 27683496 TI - External Quality Assessment Schemes in Latin America. AB - As professionals of the clinical laboratory we must generate clinically useful results, products and services for the patients' health care. Laboratories must participate in one or more proficiency testing (PT) or external quality assessment (EQA) programs as part of routine quality assurance. Nevertheless participating per se is not enough. There are critical factors to take into consideration when selecting a PT or EQA providers. In most cases the survey's providers offer assigned values obtained from consensus of results provided by the participants for comparison, it is critical to evaluate consistency of the comparison group before interpretation and decision-making. PMID- 27683497 TI - Laboratory Accreditation in Argentina. AB - Laboratory accreditation is an essential element in the healthcare system since it contributes substantially to decision-making, in the prevention, diagnosis, treatment and follow-up of the health status of the patients, as well as in the organization and management of public healthcare. Therefore, the clinical biochemistry professional works continuously to provide reliable results and contributes to the optimization of operational logistics and integration of a laboratory into the health system. ISO 15189 accreditation, ensures compliance of the laboratory to minimize instances of error through the planning, prevention, implementation, evaluation and improvement of its procedures, which provides skill areas that involve both training undergraduate and graduate professionals in clinical biochemistry. PMID- 27683498 TI - The Accreditation Experience of Clinical Laboratories and Blood Banks in Mexico. AB - The accreditation of clinical laboratories and blood banks based on ISO 15189 is now being consolidated in Mexico, and is coordinated by the Mexican accreditation entity innovative strategies, A.C. (ema) and supported by the activities of the committee of clinical laboratories and blood banks. The active participation in working groups formed by the technical committee of clinical laboratories and blood banks in specific areas, has contributed to the formulation of technical documents and criteria of evaluation that strengthen the current accreditation scheme. The national registry of evaluation (PNE) consists of technical experts and evaluators from different disciplines of clinical laboratory; the evaluators actively participate in accreditation assessment, with an ultimate goal to receive training and feedback for continuous improvement of its own performance. PMID- 27683499 TI - Experience of Implementing ISO 15189 Accreditation at a University Laboratory. AB - The present article summarizes the authors' experience with the implementation of a quality management system based on ISO 17025 and ISO 15189 standards at university laboratories. The accreditation of the analytical procedures at the Universidad Mariano Galvez represented a challenge due to the unique nature of an educational institution and the difference in nature to the standards implemented. Sample handling and care of the patient were combined to achieve an integrated management system. We explain the development of the management system, the obstacles and benefits of the system and concluding that it is possible to design a management system based on ISO 15189 for the university lab that allowed delivering results assuring technical competence to patient care and welfare. PMID- 27683500 TI - Quality Control in Screening for Infectious Diseases at Blood Banks. Rationale and Methodology. AB - Quality control procedures are indispensable to ensure the reliability of the results provided by laboratories responsible for serological screening in blood banks. International recommendations on systems of quality management classify as a top component the inclusion of two types of control: (a) internal quality control (IQC) and (b) external quality control (EQC). In EQC it is essential to have, at least, a monthly frequency of laboratory assessment. On the other hand, IQC involves the daily use of low-reactivity control sera, which should be systematically added in all run, carried out in the laboratory for each parameter. Through the IQC analysis some variations in the criteria of run acceptance and rejection may be revealed, but it is of paramount importance to ensure the previous definition of these criteria and even more importantly, the adherence to them; and that corresponds to the validation of analytical runs of each test. Since 2010 this has been, for instance, the experience of the PNCQ*, developing external quality control programmes on serology for blood banks. These programmes use samples of lyophilized sera well-characterized for the reactivity related to the parameters used for the serological screening of blood donors. The programmes have used blind panels of six samples for monthly assessments. In the last 50 assessments, which involved 68 blood banks in Brazil, a significant number of instances of non-compliance were observed in all monthly assessments. These results provide strong support to the recommendation of systematic monthly assessments. (*) National Quality Control Programme (PNCQ). PMID- 27683501 TI - Harmonization of Clinical Laboratory Test Results. AB - Clinical laboratory testing is now a global activity with laboratories no longer working in isolation but as regional and national networks, and often at international levels. We now have all of the electronic gadgetry via internet technology at our fingertips to rapidly and accurately measure and report on laboratory testing but are our test results harmonized? PMID- 27683503 TI - Harmonization Initiatives in Europe. AB - INTRODUCTION: Modern medicine is more and more based on protocols and guidelines; clinical laboratory data play very often a relevant role in these documents and for this reason the need for their harmonization is increasing. To achieve harmonized results the harmonization process must not be limited to only the analytical part, but has to include the pre- and the post-analytical phases. RESULTS: To fulfill this need the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has started several initiatives. A Working Group on harmonization of the total testing process (WG-H) has been created with the aims of: 1) surveying and summarizing national European and pan European harmonization initiatives; 2) promoting and coordinating the dissemination of especially promising harmonization initiatives among the EFLM member societies; and 3) taking initiatives to harmonize nomenclature, units and reference intervals at a European level. The activity of the WG started this year with a questionnaire targeted at surveying the status of various harmonization activities, especially those in the pre- and post-analytical phase categories, among the European laboratory medicine societies. CONCLUSIONS: Based on the results of the questionnaire, some activities promoting the dissemination of best practice in blood sampling, sample storage and transportation, in collaboration with WG on the pre-analytical phase, will be promoted, and initiatives to spread to all the European countries the use of SI units in reporting, will be undertaken. Moreover, EFLM has created a Task and Finish Group on standardization of the color coding for blood collection tube closures that is actively working to accomplish this difficult task through collaboration with manufacturers. PMID- 27683502 TI - Harmonization of Clinical Laboratory Information - Current and Future Strategies. AB - According to a patient-centered viewpoint, the meaning of harmonization in the context of laboratory medicine is that the information should be comparable irrespective of the measurement procedure used and where and/or when a measurement is made. Harmonization represents a fundamental aspect of quality in laboratory medicine as its ultimate goal is to improve patient outcomes through the provision of an accurate and actionable laboratory information. Although the initial focus has to a large extent been to harmonize and standardize analytical processes and methods, the scope of harmonization goes beyond to include all other aspects of the total testing process (TTP), such as terminology and units, report formats, reference intervals and decision limits, as well as tests and test profiles request and criteria for interpretation. Two major progresses have been made in the area of harmonization in laboratory medicine: first, the awareness that harmonization should take into consideration not only the analytical phase but all steps of the TTP, thus dealing with the request, the sample, the measurement, and the report. Second, as the processes required to achieve harmonization are complicated, a systematic approach is needed. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has played a fundamental and successful role in the development of standardized and harmonized assays, and now it should continue to work in the field through the collaboration and cooperation with many other stakeholders. PMID- 27683504 TI - The International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR) - A Pathway for Harmonization. AB - Results from clinical laboratory measurement procedures must be equivalent to enable effective use of clinical guidelines for disease diagnosis and patient management. Analytical results that are harmonized and independent of the measurement system, time, and location of testing is essential for providing adequate patient care. The key to generating harmonized results is establishing traceability to an accepted reference standard where available. Awareness of the benefits of having traceable measurement results that are harmonized has increased along with efforts to develop approaches to enable and facilitate the implementation of harmonization. Although several organizations are addressing harmonization of test procedures, centralized and cooperative global oversight is needed to ensure that the most important tests are being addressed and resources are optimally used. Working with its domestic and international partners, the American Association for Clinical Chemistry (AACC) has created an International Consortium for Harmonization of Clinical Laboratory Results. Advances in this area will improve the quality of patient care. PMID- 27683505 TI - Harmonization of Clinical Laboratory Test Results: The Role of the IVD Industry. AB - At the start of the 21st century, a dramatic change occurred in the clinical laboratory community. Concepts from Metrology, the science of measurement, began to be more carefully applied to the in vitro diagnostic (IVD) community, that is, manufacturers. A new appreciation of calibrator traceability evolved. Although metrological traceability always existed, it was less detailed and formal. The In Vitro Diagnostics Directive (IVDD) of 2003 required manufacturers to provide traceability information, proving assays were anchored to internationally accepted reference materials and/or reference methods. The intent is to ensure comparability of patient test results, regardless of the analytical system used to generate them. Results of equivalent quality allows for the practical use of electronic health records (EHRs) capture a patient's complete laboratory test history and allow healthcare providers to diagnose and treat patients, confident the test results are suitable for correct interpretation, i.e., are "fit for purpose" and reflect a real change in a patient's condition and not just "analytical noise." The healthcare benefits are obvious but harmonization of test systems poses significant challenges to the IVD Industry. Manufacturers must learn the theory of metrological traceability and apply it in a practical manner to assay calibration schemes. It's difficult to effect such a practical application because clinical laboratories do not test purified analytes using reference measurement procedures but instead deal with complex patient samples, e.g., whole blood, serum, plasma, urine, etc., using "field methods." Harmonization in the clinical laboratory is worth the effort to achieve optimal patient care. PMID- 27683506 TI - Opinion Paper: Deriving Harmonised Reference Intervals - Global Activities. AB - Harmonisation of reference intervals (RIs) refers to use of the same or common RI across different platforms and /or assays for a specified analyte. It occurs optimally for those analytes where there is sound calibration and traceability in place and evidence from a between-method comparison shows that bias would not prevent the use of a common RI. The selection of the RI will depend on various sources of information including local formal RI studies, published studies from the literature, laboratory surveys, manufacturer's product information, relevant guidelines, and mining of databases. Pre-analytical and partitioning issues, significant figures and flagging rates, are assessed for each analyte. Several countries and regions including the Nordic countries, United Kingdom, Japan, Turkey, and Australasia are using common RIs that have been determined either by direct studies or by a consensus process. In Canada, the Canadian Society of Clinical Chemists Taskforce is assessing the feasibility of establishing common reference values using the CALIPER (Canadian Laboratory Initiative on Pediatric Reference Intervals) and CHMS (The Canadian Health Measures Survey) databases as the basis. Development of platform-specific common reference values for each of the major analytical systems may be a more practical approach especially for the majority of analytes that are not standardised against a primary reference method and are not traceable to a primary or secondary reference material. We encourage laboratories to consider adopting reference intervals consistent with those used by other laboratories in your region where it is possible and appropriate for your local population. Local validation of the adopted reference interval is also recommended as per CLSI guidelines. PMID- 27683507 TI - Critical Risk Results - An Update on International Initiatives. AB - Direct communication of significant (often life-threatening) results is a universally acknowledged role of the pathology laboratory, and an important contributor to patient safety. Amongst the findings of a recent survey of 871 laboratories from 30 countries by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), only 3 tests were noted to be common to 90% of alert lists, and only 48% of laboratories consulted clinicians in developing these alert lists despite ISO15189 recommendations to do so. These findings are similar to previous national surveys demonstrating significant variation worldwide in how critical risk results are managed and also in how these protocols are developed. In order to promote "best practice" and harmonization of critical risk results management, guidelines and recommendations have been published, most recently by Clinical and Laboratory Standards Institute (CLSI) and Australasian Association of Clinical Biochemists (AACB). These statements in particular have placed strong emphasis on patient risk and risk assessment in the management of critical risk results. This focus has resulted in recommendations to adopt new terminology, the consideration of risk assessment when compiling alert tables, consultative involvement of laboratory users in setting up protocols, and the need for outcome-based evidence to support our practices. With time it is expected that emerging evidence and technological improvements will facilitate the advancement of laboratories down this path to harmonization, best practice, and improve patient safety. PMID- 27683508 TI - Using Agency Nurses to Fill RN Vacancies Within Specialized Hospice and Palliative Care. AB - The use of agency nurses offers flexibility in filling registered nurse (RN) openings during times of shortage, yet little is known about their use in specialized palliative care. In an effort to fill this knowledge gap, this study determined whether significant relationships existed between full-time and part time RN vacancies and the use of agency RNs within specialized hospices that deliver perinatal end-of-life care to women and their families in the event of miscarriage, ectopic pregnancy, or other neonatal complications resulting in death. This study used data from the 2007 National Home and Hospice Care Survey and multivariate regression methods to estimate the association between RN vacancies and agency RNs use. Approximately 13% of perinatal hospices in 2007 used agency nurses. Increases in full-time RN vacancies are associated with a significant increase in the use of agency RNs, while part-time RN vacancies are associated with a significant decrease in agency RNs. These results suggest that full-time agency RNs were used as a supplemental workforce to fill vacancies until the full-time position is recruited. However, for part-time vacancies, the responsibilities of those positions shifted onto existing staff and the position was not filled. PMID- 27683510 TI - Herbal medicine (Gyejibongneyong-hwan) for treating primary dysmenorrhoea: a protocol for a systematic review of randomised controlled trials. AB - INTRODUCTION: Gyejibongneyong-hwan (GBH), also known as Guizhi Fuling formula, and is widely used for uterine fibroids in East Asian countries. Many clinical trials assessing the efficacy and safety of GBH formula for the treatment of dysmenorrhoea have been reported. This review will assess the clinical evidence for and against the use of GBH formula as a treatment for dysmenorrhoea. It will also discuss the proposed mechanism(s) that could link herbal medicine to improvements in dysmenorrhoea. METHODS AND ANALYSIS: Fourteen databases will be searched until September 2016. We will include randomised controlled trials (RCTs) examining GBH decoctions for any type of dysmenorrhoea. All RCTs of decoctions or modified decoctions will be included. The methodological qualities of the RCTs will be assessed using the Cochrane Collaboration tool for assessing risk of bias. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. It will be updated to inform and guide healthcare practices. TRIAL REGISTRATION NUMBER: CRD42015023419. PMID- 27683511 TI - When are clinical trials beneficial for study patients and future patients? A factorial vignette-based survey of institutional review board members. AB - OBJECTIVE: The ethicists believe that the goal of clinical research is to benefit future and not current (trial) patients. Many clinicians believe that the clinical trial enrolment offers best management for their patients. The objective of our study was to identify the situations when a clinical trial is beneficial for the patients enrolled in the trial and future patients. DESIGN: Factorial vignette-based cross-sectional survey via the internet. PARTICIPANTS: Institutional review board (IRB) members of the US Medical Schools. MAIN OUTCOME MEASURES: Each participant was invited to review 9 clinical vignettes related to (1) study approval and (2) the assessment if the study is designed to help future or current patients more. RESULTS: A total of 232 IRB members from 42 institutions participated. When considering approval of the trial, we found that uncertainty about treatment effects (OR=1.13; 95% CI 1.08 to 1.19) and requirement for continuation of standard therapy (OR=3.84; 95% CI 2.7 to 5.55) were the only statistically significant factors affecting IRB members' decisions to approve the study. The odds of IRB members approving a trial increased when a trial proposed to enrol patients with life-threatening versus chronic debilitating disease (OR=2.04; 95% CI 1.47 to 2.86). We also found that similar factors affected judgements related to the assessment whether the trial will benefit future or current patients more-(1) future patients: uncertainty (OR=1.27; 95% CI 1.18 to 1.37); continuation of standard treatment (OR=1.66; 95% CI 1.07 to 2.56); seriousness of condition (OR=1.78; 95% CI 1.15 to 2.28); (2) current patients: uncertainty (OR=1.54; 95% CI 1.4 to 1.7); continuation of standard therapy (OR=2.17; 95% CI 1.39 to 3.44). CONCLUSIONS: IRB members view the proposed studies to be beneficial for current patients and future patients if there is uncertainty regarding treatment effects and if studies do not require stopping the current treatment. This finding supports the design and use of pragmatic trials which may reduce therapeutic misconception and improve trial enrolment, speeding up therapeutic discoveries. PMID- 27683509 TI - The National Early Warning Score (NEWS) for outcome prediction in emergency department patients with community-acquired pneumonia: results from a 6-year prospective cohort study. AB - OBJECTIVE: To investigate the accuracy of the National Early Warning Score (NEWS) to predict mortality and adverse clinical outcomes for patients with community acquired pneumonia (CAP) compared to standard risk scores such as the pneumonia severity index (PSI) and CURB-65. DESIGN: Secondary analysis of patients included in a previous randomised-controlled trial with a median follow-up of 6.1 years. SETTINGS: Patients with CAP included on admission to the emergency departments (ED) of 6 tertiary care hospitals in Switzerland. PARTICIPANTS: A total of 925 patients with confirmed CAP were included. NEWS, PSI and CURB-65 scores were calculated on admission to the ED based on admission data. MAIN OUTCOME MEASURE: Our primary outcome was all-cause mortality within 6 years of follow-up. Secondary outcomes were adverse clinical outcome defined as intensive care unit (ICU) admission, empyema and unplanned hospital readmission all occurring within 30 days after admission. We used regression models to study associations of baseline risk scores and outcomes with the area under the receiver operating curve (AUC) as a measure of discrimination. RESULTS: 6-year overall mortality was 45.1% (n=417) with a stepwise increase with higher NEWS categories. For 30 day and 6-year mortality prediction, NEWS showed only low discrimination (AUC 0.65 and 0.60) inferior compared to PSI and CURB-65. For prediction of ICU admission, NEWS showed moderate discrimination (AUC 0.73) and improved the prognostic accuracy of a regression model, including PSI (AUC from 0.66 to 0.74, p=0.001) and CURB-65 (AUC from 0.64 to 0.73, p=0.015). NEWS was also superior to PSI and CURB-65 for prediction of empyema, but did not well predict rehospitalisation. CONCLUSIONS: NEWS provides additional prognostic information with regard to risk of ICU admission and complications and thereby improves traditional clinical-risk scores in the management of patients with CAP in the ED setting. TRIAL REGISTRATION NUMBER: ISRCTN95122877; Post-results. PMID- 27683512 TI - Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study. AB - OBJECTIVE: A modified version of the Joint British Societies (JBS3) 'heart age' tool was introduced online to broaden access to personalised risk assessment to the general population and encourage participation in the National Health Service (NHS) Health Check programme. This study reports on its early uptake and the profiles of those who used the self-assessment tool to determine their own cardiovascular risk. DESIGN: Observational, retrospective analysis of online tool use. SETTING: Between February and July 2015, user data collected from the NHS Choices website, where the tool was hosted, were analysed anonymously using standard analytic packages. RESULTS: The online tool landing page was viewed 1.4 million times in the first 5 months, with increased activity following limited media coverage. Of the 575 782 users completing the data journey with a valid 'heart age' result, their demographic and risk factor profiles broadly resembled the population of England, although both younger users and males (60%) were over represented. Almost 50% and 79% did not know or enter their blood pressure or total cholesterol values, respectively. Estimated heart age was higher than chronological age for 79% of all users, and also for 69% of younger users under 40 years who are at low 10-year risk and not invited for NHS Health Checks. CONCLUSIONS: These data suggest a high level of public interest in self assessment of cardiovascular risk when an easily understood metric is used, although a large number of users lack awareness of their own risk factors. The heart age tool was accessed by a group not easily reached by conventional approaches yet is at high cardiovascular risk and would benefit most from early and sustained risk reduction. These are both important opportunities for interventions to educate and empower the public to manage better their cardiovascular risk and promote population-level prevention. PMID- 27683513 TI - Effects of universally offered parenting interventions for parents with infants: a systematic review. AB - OBJECTIVES: From a developmental perspective, infancy is a critical stage of life. Early childhood interventions aim to support caretakers, but the effects of universal interventions for parents with infants are unknown. The objective is to determine the effects of universal parenting interventions offered to parents with infants 0-12 months on measures of child development and parent-child relationship. DESIGN: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We extracted publications from 10 databases in June 2013, January 2015 and June 2016 and supplemented with grey and hand search. Risk of bias was assessed, and effect sizes were calculated. PARTICIPANTS: Inclusion criteria are: (1) randomised controlled trials of structured, psychosocial interventions offered to a universal population of parents with infants 0-12 months old in western OECD countries, (2) interventions that include a minimum of 3 sessions with at least half of the sessions delivered postnatally and (3) programme outcomes reported for child development or parent child relationship. RESULTS: 14 papers representing 7 studies are included. There were no statistically significant effects of the intervention for the majority of the primary outcomes across the studies. CONCLUSIONS: The findings of this review are mixed. No clear conclusions can be drawn regarding the effects of universally offered parenting interventions on child development and parent-child relationship for this age group. PMID- 27683514 TI - Predictive value of miR-210 as a novel biomarker for pre-eclampsia: a systematic review protocol. AB - INTRODUCTION: Pre-eclampsia (PE) is a serious condition affecting 3-5% of all pregnancies worldwide. However, underlying molecular pathogenesis of this disease has largely remained unknown. Recently, several studies have indicated the possibility role of microRNAs, especially miR-210, in the aetiology of PE. The aim of this systematic review is to assess the possible role of miR-210 as a novel biomarker for the prediction of PE. METHODS AND ANALYSIS: Using a combination of mesh terms 'preeclampsia', 'microRNA' and their equivalents, an electronic search will be performed for all observational studies (cross sectional, case-control and cohort) in PubMed, Web of Science, Scopus, Embase, Cochrane, LILACS and OvidSP MEDLINE from January 2005 to December 2015. Furthermore, other sources are searched, including grey literature, reference lists of relevant primary studies as well as key journals. Study selection, data extraction and quality assessment of studies will be performed independently by 2 reviewers, and any disagreement will be resolved by consensus. If sufficient data are available, it will be combined by either fixed or random effects models. We will investigate the source)s(and degree of heterogeneity using 'Heterogeneity chi2' and I2. Heterogeneity would be investigated through either subgroup analysis or metaregression. Stata V.11.1 will be used for data analysis. ETHICS AND DISSEMINATION: The results of this study are disseminated in peer-reviewed journal articles and academic presentations. Formal ethical approval is not required, since the secondary data will be collected. TRIAL REGISTRATION NUMBER: CRD42015032345. PMID- 27683515 TI - Investigation of social, demographic and health variations in the usage of prescribed and over-the-counter medicines within a large cohort (South Yorkshire, UK). AB - OBJECTIVES: Prescribed and over-the-counter (non-prescribed) medicine usage has increased in recent years; however, there has been less investigation of the socioeconomic predictors of use. This has been due to a lack of data, especially for over-the-counter medicines. Our study aims to understand how prescribed and over-the-counter medicine patterns vary by demographic, social and health characteristics within a large population cohort. DESIGN: Cross-sectional data analysis. SETTING: South Yorkshire, UK. PARTICIPANTS: 27 806 individuals from wave 1 of the Yorkshire Health Study (2010-2012). MEASURES: Individuals self reported each medicine they were taking and whether each was prescribed or not. The medicines were grouped into 14 categories (eg, cardiovascular system, infection, contraception). Negative binomial regression models were used to analyse the count of medicine usage. We included demographic (age, gender, ethnicity), social (education), health-related (body mass index, smoking, alcohol consumption, physical activity) factors and chronic health conditions (eg, stroke, anxiety and heart disease) in our analyses. RESULTS: 49% of men and 62% of women were taking medicine with the majority of this prescribed (88% and 83%, respectively). Health conditions were found to be positively associated with prescribed medicine usage, but mixed in their associated with over-the-counter medicines. Educational attainment was negatively associated with prescribed and positively associated with over-the-counter usage. CONCLUSIONS: Our study addresses a dearth of evidence to provide new insights into how behaviours in medicine usage vary by demographic, social and health-related factors. Differences in over-the-counter medicine usage by educational attainment may help our understanding of the determinants of health inequalities. PMID- 27683516 TI - Extent and pattern of burden of care and its associated factors among Eritrean families of persons living with schizophrenia: a cross-sectional study. AB - PURPOSE: To assess the caregiving burden and its associated factors among Eritrean families of persons living with schizophrenia. METHODS: A cross sectional study was conducted for 146 caregivers with their respective known patients with schizophrenia of Saint Mary's Neuropsychiatric National Referral Hospital (SMNNRH). Data were collected using Pai and Kapur's Family Burden Interview Schedule (FBIS), the Positive and Negative Syndrome Scale (PANSS) and self-prepared sociodemographic sheet. Data were analysed using SPSS V.21. Descriptive statistics, independent t-tests, one-way analysis of variance (ANOVA) and multiple regression analysis was employed to analyse the data. RESULTS: In this study, 84 (57.5%) were males and 62 (42.5%) were females. The mean age was 33.96+10.37 (median=31) for the patients and 46.76+13.96 (median=48) for the caregivers. Total mean objective score was 29.47+6.67. Family caregivers who were single (F=3.224, p<0.005, effect size (ES)=0.064), had educational level at elementary (F=5.647 p=0.001, ES=0.11), had low monthly income (t=7.727, p<0.001, ES=0.01) and were dissatisfied with family support (t=2.889, p<0.01, ES=0.01) experienced greater burden relative to the counterparts. Caregiver's age (beta=0.156; p<0.05), duration of caregiving (beta=0.131; p<0.05), monthly household family income (beta=-0.298; p<0.001), history of self-injury (beta=0.151; p=0.05), positive scale (beta=0.344; p<0.001), negative scale (beta=0.278; p<0.001) and general psychopathological scale (beta=0.146; p<0.01) emerged as significant predictors of objective burden. CONCLUSIONS: Family caregivers of a person living with schizophrenia experience a significant burden of care. Our findings highlight that there is a need of strengthening social and psychological support to reduce the caregiving burden. PMID- 27683517 TI - Decisional support for young people who self-harm: protocol for a feasibility trial. AB - INTRODUCTION: Self-harm is common in adolescents, and it is the strongest predictor of suicide. Young people who self-harm are often unsure of how and where to get help. Decision aids (DAs) have been shown to help with decisional conflict where there is uncertainty around different options. We have developed an online DA to support young people in help-seeking for self-harm. A feasibility trial will examine the acceptability of the online intervention and the ability to recruit and follow-up participants within a school setting. METHODS AND ANALYSIS: In this parallel arm, single-blind feasibility trial, 60 participants aged 12-18 years who have self-harmed in the past 12 months, will be randomised to either (1) a group receiving the online DA or (2) a control group receiving general information about feelings and emotions. Both groups will complete measures assessing decision-making and help-seeking behaviour. The school counsellor will be notified of any participants who have been randomised to ensure safeguarding for the young person. Participants in both groups will be followed up at 4 weeks, and the measures will be repeated. Qualitative interviews will be conducted with a subset of participants to explore their views and experiences of the DA and of participation in the study. ETHICS AND DISSEMINATION: Ethical approval was granted by King's College London (KCL) College Research Ethics Committee. Results of this study will help to clarify if we can recruit and administer an online decisional support intervention within a school setting for young people who self-harm. The study will inform the design and implementation of a larger randomised controlled trial to test the effectiveness of the DA. Dissemination of the study findings will target publication in peer-reviewed journals of general and special interest. The funder will be sent a report outlining the major findings of the study. TRIAL REGISTRATION NUMBER: ISRCTN11230559. PMID- 27683518 TI - Adherence to the Tobacco Control Act, 2007: presence of a workplace policy on tobacco use in bars and restaurants in Nairobi, Kenya. AB - INTRODUCTION: Despite extensive knowledge about effective tobacco control interventions, the prevalence of tobacco use in many middle- and low-income countries continues to rise. In these countries, public appreciation of levels of protection provided by laws and regulations on tobacco use and exposure to tobacco smoke is limited. After ratification of the Framework Convention on Tobacco Control, Kenya enacted the Tobacco Control Act, 2007, banning smoking in public places except in designated smoking areas. OBJECTIVE: To assess adherence to the Tobacco Control Act, 2007 by determining the presence of a workplace policy on tobacco use in bars and restaurants. METHODS: A survey of 176 liquor licensed bars and restaurants in Nairobi County was carried out. Their managers were asked about the presence of a workplace policy governing smoking of tobacco, and observations made on provisions that determine adherence to the Tobacco Control Act, 2007. RESULTS: Smoking took place in almost all bars and restaurants (150 (85%)). Half the establishments (86 (49%)) had a workplace policy governing tobacco use among employees, although a difference between bars (11 (23%)) and restaurants (75 (58%)) was recorded (p<0.001). Establishments at which managers had lower levels of education were less likely to have a workplace policy (p<0.001) and less likely to have 'no smoking' signs and designated smoking areas (p<0.005). CONCLUSIONS AND RECOMMENDATIONS: Kenya's implementation of the Tobacco Control Act, 2007 does not provide sufficient protection of patrons and workers in bars and restaurants. It is important to sensitise hospitality workers to the dangers of tobacco smoke. Bar and restaurants managers should have a minimum post secondary education level. The Tobacco Control Act, 2007 requires strengthening to ensure that bars and restaurants have a smoke-free environment. PMID- 27683519 TI - Patient-controlled hospital admission for patients with severe mental disorders: study protocol for a nationwide prospective multicentre study. AB - INTRODUCTION: Patient-controlled hospital admission for individuals with severe mental disorders is a novel approach in mental healthcare. Patients can admit themselves to a hospital unit for a short stay without being assessed by a psychiatrist or contacting the emergency department. Previous studies assessing the outcomes of patient-controlled hospital admission found trends towards reduction in the use of coercive measures and length of hospital stay; however, these studies have methodological shortcomings and small sample sizes. Larger studies are needed to estimate the effect of patient-controlled hospital admission on the use of coercion and of healthcare services. DESIGN AND METHODS: We aim to recruit at least 315 patients who are offered a contract for patient controlled hospital admissions in eight different hospitals in Denmark. Patients will be followed-up for at least 1 year to compare the use of coercive measures and of healthcare services, the use of medications and suicidal behaviour. Descriptive statistics will be used to investigate hospitalisations, global assessment of functioning (GAF) and patient satisfaction with treatment. To minimise selection bias, we will match individuals using patient-controlled hospital admission and controls with a 1:5 ratio via a propensity score based on the following factors: sex, age group, primary diagnosis, substance abuse as secondary diagnosis, coercion, number of psychiatric bed days, psychiatric history, urbanity and suicidal behaviour. Additionally, a historical control study will be undertaken in which patients serve as their own control group prior to index date. ETHICS AND DISSEMINATION: The study has been approved by The Danish Health and Medicines Authority (j.nr.: 3-3013-934/1/) and by The Danish Data Protection Agency (j.nr.: 2012-58-0004). The study was categorised as a register study by The Danish Health Research Ethics Committee and therefore no further approval was needed (j.nr.: H-2-2014-FSP70). Findings will be disseminated through scientific publications, presentations and in a PhD thesis. PMID- 27683520 TI - School restrictions on outdoor activities and weight status in adolescent children after Japan's 2011 Fukushima Nuclear Power Plant disaster: a mid-term to long-term retrospective analysis. AB - OBJECTIVE: Radiation fears following Japan's 2011 Fukushima nuclear disaster affected levels of physical activity in local children. We assessed the postdisaster versus predisaster weight status in school children and evaluated to what extent school restrictions on outdoor activities that were intended to reduce radiation exposure risk affected child weight. PARTICIPANTS: We considered children aged 13-15 years from 4 of the 5 secondary schools in Soma City (n=1030, 99.1% of all children in the city), located in 35-50 km from the Fukushima nuclear plant, postdisaster (2012 and 2015) and predisaster (2010). METHODS: Weight status, in terms of body mass index (BMI), percentage of overweight (POW) and incidence of obesity and underweight (defined as a POW >=20% and <=-20%, respectively) were examined and compared predisaster and postdisaster using regression models. We also constructed models to assess the impact of school restrictions on outdoor activity on weight status. RESULTS: After adjustment for covariates, a slight decrease in mean BMI and POW was detected in females in 2012 (-0.37, 95% CI -0.68 to -0.06; and -1.97, 95% CI -3.57 to -0.36, respectively). For male children, obesity incidence increased in 2012 (OR for obesity: 1.45, 95% CI 1.02 to 2.08). Compared with predisaster weight status, no significant weight change was identified in 2015 in either males or females. School restrictions on outdoor activities were not significantly associated with weight status. CONCLUSIONS: 4 years following the disaster, weight status has recovered to the predisaster levels for males and females; however, a slight decrease in weight in females and a slight increase in risk of obesity were observed in males 1 year following the disaster. Our findings could be used to guide actions taken during the early phase of a radiological disaster to manage the postdisaster health risks in adolescent children. PMID- 27683522 TI - The Hungarian Society of Laboratory Medicine - Serving Patients for 70 Years. PMID- 27683521 TI - Impacts of the 2011 Fukushima nuclear accident on emergency medical service times in Soma District, Japan: a retrospective observational study. AB - OBJECTIVE: To assess the influence of the 3.11 triple disaster (earthquake, tsunami and nuclear accident) on the emergency medical service (EMS) system in Fukushima. METHODS: Total EMS time (from EMS call to arrival at a hospital) was assessed in the EMS system of Soma district, located 10-40 km north of the nuclear plant, from 11 March to 31 December 2011. We defined the affected period as when total EMS time was significantly extended after the disasters compared with the historical control data from 1 January 2009 to 10 March 2011. To identify risk factors associated with the extension of total EMS time after the disasters, we investigated trends in 3 time segments of total EMS time; response time, defined as time from an EMS call to arrival at the location, on-scene time, defined as time from arrival at the location to departure, and transport time, defined as time from departure from the location to arrival at a hospital. RESULTS: For the affected period from week 0 to week 11, the median total EMS time was 36 (IQR 27-52) minutes, while that in the predisaster control period was 31 (IQR 24-40) min. The percentage of transports exceeding 60 min in total EMS time increased from 8.2% (584/7087) in the control period to 22.2% (151/679) in the affected period. Among the 3 time segments, there was the most change in transport time (standardised mean difference: 0.41 vs 0.13-0.17). CONCLUSIONS: EMS transport was significantly delayed for ~3 months, from week 1 to 11 after the 3.11 triple disaster. This delay may be attributed to malfunctioning emergency hospitals after the triple disaster. PMID- 27683523 TI - Biochemical Markers of Myocardial Damage. AB - Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid 1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in clinical practice. PMID- 27683524 TI - Non-Invasive Assessment of Viability in Human Embryos Fertilized in Vitro. AB - Human reproduction is a relatively inefficient process and therefore the number of infertile couples is high. Assisted reproductive technologies (ART) have facilitated the birth of over five million children worldwide. ART, however, superimposes its own relative inefficiency on the preexisting inefficiency of normal reproduction. The efficiency (expressed as pregnancy rate) is generally not more than 30%. Modern reproductive medicine is gradually moving from multiple embryo transfer to the transfer of a single embryo, mainly because of obvious and unwanted side effects of multiple embryo transfer (e.g. "epidemic" multiple pregnancies). This concept, however, requires a fast, professional selection of the most viable embryo during the first few days of ART. Thus the aim of a modern ART is the safe transfer of a healthy, viable, single embryo. Accurate and rapid methods of quantifying embryo viability are needed to reach this goal. Methodological advances have the potential to make an important contribution, and there has been a drive to develop alternative non-invasive methods to better meet clinical needs. Metabolic and genetic profiling of spent embryo culture (SEC) media should offer an exceptional opportunity for the assessment of embryo viability. The current review focuses on the latest non-invasive diagnostic approaches for pre-implantation viability assessment of in vitro fertilized embryos. PMID- 27683525 TI - The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders. AB - The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender specific reference ranges. PMID- 27683528 TI - Clinical Laboratories - Production Factories or Specialized Diagnostic Centers. AB - Since a large proportion of medical decisions are based on laboratory results, clinical laboratories should meet the increasing demand of clinicians and their patients. Huge central laboratories may process over 10 million tests annually; they act as production factories, measuring emergency and routine tests with sufficient speed and accuracy. At the same time, they also serve as specialized diagnostic centers where well-trained experts analyze and interpret special test results. It is essential to improve and constantly monitor this complex laboratory service, by several methods. Sample transport by pneumatic tube system, use of an advanced laboratory information system and point-of-care testing may result in decreased total turnaround time. The optimization of test ordering may result in a faster and more cost-effective laboratory service. Autovalidation can save time for laboratory specialists, when the analysis of more complex results requires their attention. Small teams of experts responsible for special diagnostic work, and their interpretative reporting according to predetermined principles, may help to minimize subjectivity of these special reports. Although laboratory investigations have become so diversely developed in the past decades, it is essential that the laboratory can provide accurate results relatively quickly, and that laboratory specialists can support the diagnosis and monitoring of patients by adequate interpretation of esoteric laboratory methods. PMID- 27683530 TI - Alan McGlennan: Happy despite appearances. PMID- 27683527 TI - Interpretation of Blood Microbiology Results - Function of the Clinical Microbiologist. AB - The proper use and interpretation of blood microbiology results may be one of the most challenging and one of the most important functions of clinical microbiology laboratories. Effective implementation of this function requires careful consideration of specimen collection and processing, pathogen detection techniques, and prompt and precise reporting of identification and susceptibility results. The responsibility of the treating physician is proper formulation of the analytical request and to provide the laboratory with complete and precise patient information, which are inevitable prerequisites of a proper testing and interpretation. The clinical microbiologist can offer advice concerning the differential diagnosis, sampling techniques and detection methods to facilitate diagnosis. Rapid detection methods are essential, since the sooner a pathogen is detected, the better chance the patient has of getting cured. Besides the gold standard blood culture technique, microbiologic methods that decrease the time in obtaining a relevant result are more and more utilized today. In the case of certain pathogens, the pathogen can be identified directly from the blood culture bottle after propagation with serological or automated/semi-automated systems or molecular methods or with MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass spectrometry). Molecular biology methods are also suitable for the rapid detection and identification of pathogens from aseptically collected blood samples. Another important duty of the microbiology laboratory is to notify the treating physician immediately about all relevant information if a positive sample is detected. The clinical microbiologist may provide important guidance regarding the clinical significance of blood isolates, since one-third to one-half of blood culture isolates are contaminants or isolates of unknown clinical significance. To fully exploit the benefits of blood culture and other (non- culture based) diagnoses, the microbiologist and the clinician should interact directly. PMID- 27683531 TI - Foreword of the Editor. PMID- 27683526 TI - Deficiencies of the Natural Anticoagulants - Novel Clinical Laboratory Aspects of Thrombophilia Testing. AB - Venous thrombosis is a typical common complex disease as acquired and genetic causes play a role in its development. The different "loss of function" mutations of the natural anticoagulant system lead to antithrombin (AT), protein C (PC) and protein S (PS) deficiencies. Since thrombophilia testing has high cost and it has several methodological issues (analytical, pre-analytical), which makes the interpretation of results difficult, considerations should be made on the indications of testing, on the parameters that are measured and on the best available method to use. The latest guideline on clinical and laboratory management of thrombophilia kept the relatively old laboratory recommendations unchanged. This is partly because of the existence of unresolved problems with the laboratory tests used for diagnosis. Based on the literature and our previous research here we discuss the unresolved problems, the recently raised questions and issues concerning AT, PC and PS laboratory diagnosis and summarize the recent findings in molecular genetic investigations. PMID- 27683529 TI - Adding Value in the Postanalytical Phase. AB - Apart from maintaining the highest quality of analytical test results, laboratories are now getting more focused on how to achieve the greatest impact of laboratory results on their patient's outcome. Laboratory professionals are now in the learning phase of implementing new practices at different steps of the extra-analytical phases of the testing process where laboratories used to contribute seldom, only sporadically. Recently, the achievable levels of harmonization and responsible contributors at various steps of the testing process have also been proposed. Based on this proposal some tasks of the extra analytical phase should become primarily the responsibility of laboratories with the involvement of clinicians, like additive testing, individualized interpretative commenting and reporting results with clinical urgency in postanalytical (PA) phase. These tasks can be good targets to start with or to increase patient outcome-oriented extra-analytical activities of laboratories. The status of the present practice of the PA activities for which laboratories proposed to be primarily responsible in the testing process - laboratory-driven PA tasks - will be reviewed below. In addition, approaches of quality assessment (QA) with quality specifications of these laboratory-driven PA tasks and the available best practice recommendations in the light of the achievable level of harmonization will be discussed. Laboratory professionals are encouraged to improve their methodological, theoretical and communicational skills and take the lead and participate in the discussed PA activities that can assist in translating laboratory test results into clinical meaning and thereby lead to better clinical utilization of laboratory test results. PMID- 27683532 TI - The World is Changing - Are We Ready? PMID- 27683534 TI - Can Natriuretic Peptides be Used to Guide Therapy? AB - Over the last 15 years, the hypothesis that intensified treatment directed at reducing natriuretic peptide (NP) concentrations may improve the outcomes of patients with heart failure (HF) has been scrutinized in several prospective clinical trials, with conflicting results. Collectively, however, the data suggest that NP concentrations may be useful in guiding HF management and improving HF-related morbidity and mortality. In this review, we summarize the existing data investigating the use of NPs as targets for outpatient HF therapy. We focus on the information gathered in randomized clinical trials and comprehensive meta-analyses, and also on the recommendations of international guidelines (primarily guidelines from the European Society of Cardiology and the American College of Cardiology/American Heart Association). Although the results for this approach are promising overall, additional well-designed prospective randomized controlled trials (e.g., the GUIDE-IT trial) are necessary to confirm or refute the utility of NP-guided outpatient HF management. PMID- 27683533 TI - Analytical Issues with Natriuretic Peptides - has this been Overly Simplified? AB - Natriuretic peptides (NPs) were first described as cardiac biomarkers more than two decades ago. Since that time, numerous studies have confirmed NPs' diagnostic and prognostic utilities as biomarkers of myocardial function. However, we must now admit that despite the NPs' relatively long period of use in clinical practice, our understanding of the biochemistry and the variety of circulating forms of NPs, as well as of their potential as biomarkers, remains far from being complete and comprehensive. The highly complex nature and wide diversity of circulating forms of NPs make their accurate measurements in plasma far more complex than initially believed. A highly simplistic view of the NPs' use is that elevated values of NPs indicate the severity of heart failure and thus reflect the prognosis. However, as shown by a variety of studies, deep understanding of how the NP system works will be required for correct interpretation of test results in routine practice of cardiovascular disease. In this review, we summarize the recent advances in understanding of the complexity of the NP system and discuss related analytical issues, which open new horizons, as well as challenges for clinical diagnostics. PMID- 27683535 TI - High Sensitivity Cardiac Troponin Assays - How to Implement them Successfully. AB - High sensitivity troponin (hsTn) assays provide an unprecedented opportunity to improve the detection and treatment of cardiac injury from coronary and non coronary causes. They may also play a role in guiding the primary and secondary prevention of cardiovascular disease. However, to derive maximal benefit from their use, careful planning for the implementation of these new assays is required. In this manuscript, we will discuss actions that can be taken during hsTn pre-implementation, implementation and post-implementation phases. Key concepts for consideration in the pre-implementation phase include: the establishment of a multi-disciplinary implementation team; development of quality control procedures; education of clinical staff; modification of existing clinical workflow and provision of computerized decision support. Strategies for ensuring successful implementation and post-implementation phases will also be discussed. PMID- 27683536 TI - Soluble ST2 and Galectin-3: What We Know and Don't Know Analytically. AB - The proteins soluble ST2 (sST2) and galectin-3 are currently gaining mounting interest as candidate biomarkers in cardiac disease. Both, sST2 and galectin-3 have been included in the 2013 ACCF/AHA guideline for additive risk stratification of patients with acute and chronic heart failure. The aim of this review is to provide information on analytical considerations of measuring circulating sST2 and galectin-3 including knowledge on in vitro stability, biological variation and reference ranges of both analytes. PMID- 27683538 TI - Emerging and Disruptive Technologies. AB - Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home testing formats), new types of specimens (e.g., cell free DNA), big biology/data (e.g., million genome projects), and new regulations (e.g., for laboratory developed tests). In addition, there are many emerging technologies (e.g., planar arrays, mass spectrometry) that might find even broader application in the future and therefore also disrupt current practice. One interesting source of disruptive technology may prove to be the Qualcomm Tricorder XPrize, currently in its final stages. PMID- 27683537 TI - ST2 and Galectin-3: Ready for Prime Time? AB - ST2 and galectin-3 are emerging biomarkers in the field of heart failure and have been extensively studied, and that whether they provide additional prognostic value on top of the clinical models and the gold standard in HF, (NT-pro)BNP. Our aim was to provide a comprehensive review of these emerging HF-related biomarkers in chronic, acute and incident heart failure. Regardless of the type of heart failure, both biomarkers seem to have an additional effect on top of the clinical model including natriuretic peptides. Strategies that combine multiple biomarkers may ultimately prove to be beneficial in the guidance of HF therapy in the future. However, additional prognostic value appears to be limited, and what we need is to prospectively test the consistent observations, which then might lead to the implementation of ST2 and galectin-3 in heart failure algorithms. PMID- 27683539 TI - Converting Multi-Shell and Diffusion Spectrum Imaging to High Angular Resolution Diffusion Imaging. AB - Multi-shell and diffusion spectrum imaging (DSI) are becoming increasingly popular methods of acquiring diffusion MRI data in a research context. However, single-shell acquisitions, such as diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI), still remain the most common acquisition schemes in practice. Here we tested whether multi-shell and DSI data have conversion flexibility to be interpolated into corresponding HARDI data. We acquired multi-shell and DSI data on both a phantom and in vivo human tissue and converted them to HARDI. The correlation and difference between their diffusion signals, anisotropy values, diffusivity measurements, fiber orientations, connectivity matrices, and network measures were examined. Our analysis result showed that the diffusion signals, anisotropy, diffusivity, and connectivity matrix of the HARDI converted from multi-shell and DSI were highly correlated with those of the HARDI acquired on the MR scanner, with correlation coefficients around 0.8~0.9. The average angular error between converted and original HARDI was 20.7 degrees at voxels with signal-to-noise ratios greater than 5. The network topology measures had less than 2% difference, whereas the average nodal measures had a percentage difference around 4~7%. In general, multi-shell and DSI acquisitions can be converted to their corresponding single-shell HARDI with high fidelity. This supports multi-shell and DSI acquisitions over HARDI acquisition as the scheme of choice for diffusion acquisitions. PMID- 27683540 TI - Synapse-Centric Mapping of Cortical Models to the SpiNNaker Neuromorphic Architecture. AB - While the adult human brain has approximately 8.8 * 10(10) neurons, this number is dwarfed by its 1 * 10(15) synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows 4* more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously. PMID- 27683541 TI - Extracellularly Recorded Somatic and Neuritic Signal Shapes and Classification Algorithms for High-Density Microelectrode Array Electrophysiology. AB - High-density microelectrode arrays (HDMEA) have been recently introduced to study principles of neural function at high spatial resolution. However, the exact nature of the experimentally observed extracellular action potentials (EAPs) is still incompletely understood. The soma, axon and dendrites of a neuron can all exhibit regenerative action potentials that could be sensed with HDMEA electrodes. Here, we investigate the contribution of distinct neuronal sources of activity in HDMEA recordings from low-density neuronal cultures. We recorded EAPs with HDMEAs having 11,011 electrodes and then fixed and immunostained the cultures with beta3-tubulin for high-resolution fluorescence imaging. Immunofluorescence images overlaid with the activity maps showed EAPs both at neuronal somata and distal neurites. Neuritic EAPs had mostly narrow triphasic shapes, consisting of a positive, a pronounced negative peak and a second positive peak. EAPs near somata had wide monophasic or biphasic shapes with a main negative peak, and following optional positive peak. We show that about 86% of EAP recordings consist of somatic spikes, while the remaining 14% represent neuritic spikes. Furthermore, the adaptation of the waveform shape during bursts of these neuritic spikes suggested that they originate from axons, rather than from dendrites. Our study improves the understanding of HDMEA signals and can aid in the identification of the source of EAPs. PMID- 27683542 TI - The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells. AB - N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma 1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain. PMID- 27683545 TI - Construction and Operation of a High-Speed, High-Precision Eye Tracker for Tight Stimulus Synchronization and Real-Time Gaze Monitoring in Human and Animal Subjects. AB - Measurements of the fast and precise movements of the eye-critical to many vision, oculomotor, and animal behavior studies-can be made non-invasively by video oculography. The protocol here describes the construction and operation of a research-grade video oculography system with ~0.1 degrees precision over the full typical viewing range at over 450 Hz with tight synchronization with stimulus onset. The protocol consists of three stages: (1) system assembly, (2) calibration for both cooperative, and for minimally cooperative subjects (e.g., animals or infants), and (3) gaze monitoring and recording. PMID- 27683543 TI - How to Evaluate Phase Differences between Trial Groups in Ongoing Electrophysiological Signals. AB - A growing number of studies endeavor to reveal periodicities in sensory and cognitive functions, by comparing the distribution of ongoing (pre-stimulus) oscillatory phases between two (or more) trial groups reflecting distinct experimental outcomes. A systematic relation between the phase of spontaneous electrophysiological signals, before a stimulus is even presented, and the eventual result of sensory or cognitive processing for that stimulus, would be indicative of an intrinsic periodicity in the underlying neural process. Prior studies of phase-dependent perception have used a variety of analytical methods to measure and evaluate phase differences, and there is currently no established standard practice in this field. The present report intends to remediate this need, by systematically comparing the statistical power of various measures of "phase opposition" between two trial groups, in a number of real and simulated experimental situations. Seven measures were evaluated: one parametric test (circular Watson-Williams test), and three distinct measures of phase opposition (phase bifurcation index, phase opposition sum, and phase opposition product) combined with two procedures for non-parametric statistical testing (permutation, or a combination of z-score and permutation). While these are obviously not the only existing or conceivable measures, they have all been used in recent studies. All tested methods performed adequately on a previously published dataset (Busch et al., 2009). On a variety of artificially constructed datasets, no single measure was found to surpass all others, but instead the suitability of each measure was contingent on several experimental factors: the time, frequency, and depth of oscillatory phase modulation; the absolute and relative amplitudes of post-stimulus event-related potentials for the two trial groups; the absolute and relative trial numbers for the two groups; and the number of permutations used for non-parametric testing. The concurrent use of two phase opposition measures, the parametric Watson-Williams test and a non-parametric test based on summing inter-trial coherence values for the two trial groups, appears to provide the most satisfactory outcome in all situations tested. Matlab code is provided to automatically compute these phase opposition measures. PMID- 27683544 TI - Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation. AB - Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF's effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF's function. PMID- 27683546 TI - Bumblebees Perform Well-Controlled Landings in Dim Light. AB - To make a smooth touchdown when landing, an insect must be able to reliably control its approach speed as well as its body and leg position-behaviors that are thought to be regulated primarily by visual information. Bumblebees forage and land under a broad range of light intensities and while their behavior during the final moments of landing has been described in detail in bright light, little is known about how this is affected by decreasing light intensity. Here, we investigate this by characterizing the performance of bumblebees, B. terrestris, landing on a flat platform at two different orientations (horizontal and vertical) and at four different light intensities (ranging from 600 lx down to 19 lx). As light intensity decreased, the bees modified their body position and the distance at which they extended their legs, suggesting that the control of landing in these insects is visually mediated. Nevertheless, the effect of light intensity was small and the landings were still well controlled, even in the dimmest light. We suggest that the changes in landing behavior that occurred in dim light might represent adaptations that allow the bees to perform smooth landings across the broad range of light intensities at which they are active. PMID- 27683549 TI - What pediatric nonprogressors and natural SIV hosts teach us about HIV. AB - A subset of HIV-infected children shows an unusually benign course of infection that recapitulates key immunological aspects of the natural SIV infection of sooty mangabeys (Muenchhoff et al.). PMID- 27683548 TI - Behavioral and TMS Markers of Action Observation Might Reflect Distinct Neuronal Processes. AB - Transcranial magnetic stimulation (TMS) studies have shown that observing an action induces muscle-specific changes in corticospinal excitability. From a signal detection theory standpoint, this pattern can be related to sensitivity, which here would measure the capacity to distinguish between two action observation conditions. In parallel to these TMS studies, action observation has also been linked to behavioral effects such as motor priming and interference. It has been hypothesized that behavioral markers of action observation could be related to TMS markers and thus represent a potentially cost-effective mean of assessing the functioning of the action-perception system. However, very few studies have looked at possible relationships between these two measures. The aim of this study was to investigate if individual differences in sensitivity to action observation could be related to the behavioral motor priming and interference effects produced by action observation. To this end, 14 healthy participants observed index and little finger movements during a TMS task and a stimulus-response compatibility task. Index muscle displayed sensitivity to action observation, and action observation resulted in significant motor priming+interference, while no significant effect was observed for the little finger in both task. Nevertheless, our results indicate that the sensitivity measured in TMS was not related to the behavioral changes measured in the stimulus-response compatibility task. Contrary to a widespread assumption, the current results indicate that individual differences in physiological and behavioral markers of action observation may be unrelated. This could have important impacts on the potential use of behavioral markers in place of more costly physiological markers of action observation in clinical settings. PMID- 27683547 TI - Causal Interactions between Frontal(theta) - Parieto-Occipital(alpha2) Predict Performance on a Mental Arithmetic Task. AB - Many neuroimaging studies have demonstrated the different functional contributions of spatially distinct brain areas to working memory (WM) subsystems in cognitive tasks that demand both local information processing and interregional coordination. In WM cognitive task paradigms employing electroencephalography (EEG), brain rhythms such as theta and alpha have been linked to specific functional roles over given brain areas, but their functional coupling has not been extensively studied. Here we analyzed an arithmetic task with five cognitive workload levels (CWLs) and demonstrated functional/effective coupling between the two WM subsystems: the central executive located over frontal (F) brain areas that oscillates on the dominant theta rhythm (Frontal(theta)/F(theta)) and the storage buffer located over parieto-occipital (PO) brain areas that operates on the alpha2 dominant brain rhythm (Parieto Occipital(alpha2)/PO(alpha2)). We focused on important differences between and within WM subsystems in relation to behavioral performance. A repertoire of brain connectivity estimators was employed to elucidate the distinct roles of amplitude, phase within and between frequencies, and the hierarchical role of functionally specialized brain areas related to the task. Specifically, for each CWL, we conducted a) a conventional signal power analysis within both frequency bands at F(theta) and PO(alpha2), b) the intra- and inter-frequency phase interactions between F(theta) and PO(alpha2), and c) their causal phase and amplitude relationship. We found no significant statistical difference of signal power or phase interactions between correct and wrong answers. Interestingly, the study of causal interactions between F(theta) and PO(alpha2) revealed frontal brain region(s) as the leader, while the strength differentiated between correct and wrong responses in every CWL with absolute accuracy. Additionally, zero time lag between bilateral F(theta) and right PO(a2) could serve as an indicator of mental calculation failure. Overall, our study highlights the significant role of coordinated activity between F(theta) and PO(alpha2) via their causal interactions and the timing for arithmetic performance. PMID- 27683551 TI - Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation. AB - De novo lipogenesis (DNL), the conversion of glucose and other substrates to lipids, is often associated with ectopic lipid accumulation, metabolic stress, and insulin resistance, especially in the liver. However, organ-specific DNL can also generate distinct lipids with beneficial metabolic bioactivity, prompting a great interest in their use for the treatment of metabolic diseases. Palmitoleate (PAO), one such bioactive lipid, regulates lipid metabolism in liver and improves glucose utilization in skeletal muscle when it is generated de novo from the obese adipose tissue. We show that PAO treatment evokes an overall lipidomic remodeling of the endoplasmic reticulum (ER) membranes in macrophages and mouse tissues, which is associated with resistance of the ER to hyperlipidemic stress. By preventing ER stress, PAO blocks lipid-induced inflammasome activation in mouse and human macrophages. Chronic PAO supplementation also lowers systemic interleukin-1beta (IL-1beta) and IL-18 concentrations in vivo in hyperlipidemic mice. Moreover, PAO prevents macrophage ER stress and IL-1beta production in atherosclerotic plaques in vivo, resulting in a marked reduction in plaque macrophages and protection against atherosclerosis in mice. These findings demonstrate that oral supplementation with a product of DNL such as PAO can promote membrane remodeling associated with metabolic resilience of intracellular organelles to lipid stress and limit the progression of atherosclerosis. These findings support therapeutic PAO supplementation as a potential preventive approach against complex metabolic and inflammatory diseases such as atherosclerosis, which warrants further studies in humans. PMID- 27683550 TI - Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection. AB - Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naive children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults. PMID- 27683552 TI - Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial. AB - Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm(3)/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors. PMID- 27683553 TI - Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria. AB - Cerebral malaria is a leading cause of global morbidity and mortality. Interventions targeting the underlying pathophysiology of cerebral malaria may improve outcomes compared to treatment with antimalarials alone. Microvascular leak plays an important role in the pathogenesis of cerebral malaria. The angiopoietin (Ang)-Tie-2 system is a critical regulator of vascular function. We show that Ang-1 expression and soluble Tie-2 expression were associated with disease severity and outcome in a prospective study of Ugandan children with severe malaria and in a preclinical murine model of experimental cerebral malaria. Ang-1 was necessary for maintenance of vascular integrity and survival in a mouse model of cerebral malaria. Therapeutic administration of Ang-1 preserved blood-brain barrier integrity and, in combination with artesunate treatment, improved survival beyond that with artesunate alone. These data define a role for dysregulation of the Ang-Tie-2 axis in the pathogenesis of cerebral malaria and support the evaluation of Ang-Tie-2-based interventions as potential adjunctive therapies for treating severe malaria. PMID- 27683555 TI - The Dissociation between Polarity, Semantic Orientation, and Emotional Tone as an Early Indicator of Cognitive Impairment. AB - The present study aims to identify early cognitive impairment through the efficient use of therapies that can improve the quality of daily life and prevent disease progress. We propose a methodology based on the hypothesis that the dissociation between oral semantic expression and the physical expressions, facial gestures, or emotions transmitted in a person's tone of voice is a possible indicator of cognitive impairment. Experiments were carried out with phrases, analyzing the semantics of the message, and the tone of the voice of patients through unstructured interviews in healthy people and patients at an early Alzheimer's stage. The results show that the dissociation in cognitive impairment was an effective indicator, arising from patterns of inconsistency between the analyzed elements. Although the results of our study are encouraging, we believe that further studies are necessary to confirm that this dissociation is a probable indicator of cognitive impairment. PMID- 27683556 TI - Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy. AB - : We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy. SIGNIFICANCE: It is unclear whether hypermutated glioblastomas are susceptible to checkpoint blockade in adults. Herein, we provide proof of principle that glioblastomas with DNA-repair defects treated with checkpoint blockade may result in CNS immune activation, leading to clinically and immunologically significant responses. These patients may represent a genomically stratified group for whom immunotherapy could be considered. Cancer Discov; 6(11); 1230-6. (c)2016 AACR.See related commentary by Snyder and Wolchok, p. 1210This article is highlighted in the In This Issue feature, p. 1197. PMID- 27683559 TI - Changes of Femoral Photolethysmographic Waveform Characteristics in Anesthetized Dogs with Increased Blood Pressure Induced by Epinephrine. AB - BACKGROUND: Blood pressure (BP) has been proven to play an important role in changes of the morphology of a pulse waveform. However, the extent of change of the morphology because of BP signaling has yet to be accurately confirmed. OBJECTIVES: This study aims to disclose the accurate effect of BP on the changes in the morphology of the pulse waveform. METHODS: Two dogs' invasive intraventricular BP (varied by ejecting different doses of epinephrine) and their femoral arterial pulse waveform (FAPW) signals were synchronously recorded. For each BP increase, a normalized single cardiac beat pulse from the FAPW signal was fitted by five Gaussian curves and the changes in the Gaussian parameters (height, peak position, and time support) were observed. RESULTS: The height parameter increased while the position and time support parameters decreased with increasing systolic BP (SBP). The height ratio and the peak intervals between the first two components decreased with increasing SBP. CONCLUSIONS: These results may contribute to the better understanding of the underlying changes of arterial pulse properties at different BP levels and demonstrate the potential application value of the Gaussian fitting method for clinically assessing pulse morphology and evaluating the well-being of artery system. PMID- 27683557 TI - TGFbeta1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer. AB - : Programmed death-1 (PD-1) is a coinhibitory receptor that downregulates the activity of tumor-infiltrating lymphocytes (TIL) in cancer and of virus-specific T cells in chronic infection. The molecular mechanisms driving high PD-1 expression on TILs have not been fully investigated. We demonstrate that TGFbeta1 enhances antigen-induced PD-1 expression through SMAD3-dependent, SMAD2 independent transcriptional activation in T cells in vitro and in TILs in vivo The PD-1hi subset seen in CD8+ TILs is absent in Smad3-deficient tumor-specific CD8+ TILs, resulting in enhanced cytokine production by TILs and in draining lymph nodes and antitumor activity. In addition to TGFbeta1's previously known effects on T-cell function, our findings suggest that TGFbeta1 mediates T-cell suppression via PD-1 upregulation in the tumor microenvironment (TME). They highlight bidirectional cross-talk between effector TILs and TGFbeta-producing cells that upregulates multiple components of the PD-1 signaling pathway to inhibit antitumor immunity. SIGNIFICANCE: Engagement of the coinhibitory receptor PD-1 or its ligand, PD-L1, dramatically inhibits the antitumor function of TILs within the TME. Our findings represent a novel immunosuppressive function of TGFbeta and demonstrate that TGFbeta1 allows tumors to evade host immune responses in part through enhanced SMAD3-mediated PD-1 expression on TILs. Cancer Discov; 6(12); 1366-81. (c)2016 AACRThis article is highlighted in the In This Issue feature, p. 1293. PMID- 27683554 TI - Toward an Integration of Deep Learning and Neuroscience. AB - Neuroscience has focused on the detailed implementation of computation, studying neural codes, dynamics and circuits. In machine learning, however, artificial neural networks tend to eschew precisely designed codes, dynamics or circuits in favor of brute force optimization of a cost function, often using simple and relatively uniform initial architectures. Two recent developments have emerged within machine learning that create an opportunity to connect these seemingly divergent perspectives. First, structured architectures are used, including dedicated systems for attention, recursion and various forms of short- and long term memory storage. Second, cost functions and training procedures have become more complex and are varied across layers and over time. Here we think about the brain in terms of these ideas. We hypothesize that (1) the brain optimizes cost functions, (2) the cost functions are diverse and differ across brain locations and over development, and (3) optimization operates within a pre-structured architecture matched to the computational problems posed by behavior. In support of these hypotheses, we argue that a range of implementations of credit assignment through multiple layers of neurons are compatible with our current knowledge of neural circuitry, and that the brain's specialized systems can be interpreted as enabling efficient optimization for specific problem classes. Such a heterogeneously optimized system, enabled by a series of interacting cost functions, serves to make learning data-efficient and precisely targeted to the needs of the organism. We suggest directions by which neuroscience could seek to refine and test these hypotheses. PMID- 27683558 TI - Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues. AB - This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration "Botanical Guidance." The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain. PMID- 27683560 TI - Contribution of Post-translational Phosphorylation to Sarcomere-Linked Cardiomyopathy Phenotypes. AB - Secondary shifts develop in post-translational phosphorylation of sarcomeric proteins in multiple animal models of inherited cardiomyopathy. These signaling alterations together with the primary mutation are predicted to contribute to the overall cardiac phenotype. As a result, identification and integration of post translational myofilament signaling responses are identified as priorities for gaining insights into sarcomeric cardiomyopathies. However, significant questions remain about the nature and contribution of post-translational phosphorylation to structural remodeling and cardiac dysfunction in animal models and human patients. This perspective essay discusses specific goals for filling critical gaps about post-translational signaling in response to these inherited mutations, especially within sarcomeric proteins. The discussion focuses primarily on pre clinical analysis of animal models and defines challenges and future directions in this field. PMID- 27683561 TI - MYBPC1, an Emerging Myopathic Gene: What We Know and What We Need to Learn. AB - Myosin Binding Protein-C (MyBP-C) comprises a family of accessory proteins that includes the cardiac, slow skeletal, and fast skeletal isoforms. The three isoforms share structural and sequence homology, and localize at the C-zone of the sarcomeric A-band where they interact with thick and thin filaments to regulate the cycling of actomyosin crossbridges. The cardiac isoform, encoded by MYBPC3, has been extensively studied over the last several decades due to its high mutational rate in congenital hypertrophic and dilated cardiomyopathy. It is only recently, however, that the MYBPC1 gene encoding the slow skeletal isoform (sMyBP-C) has gained attention. Accordingly, during the last 5 years it has been shown that MYBPC1 undergoes extensive exon shuffling resulting in the generation of multiple slow variants, which are co-expressed in different combinations and amounts in both slow and fast skeletal muscles. The sMyBP-C variants are subjected to PKA- and PKC-mediated phosphorylation in constitutive and alternatively spliced sites. More importantly, missense, and nonsense mutations in MYBPC1 have been directly linked with the development of severe and lethal forms of distal arthrogryposis myopathy and muscle tremors. Currently, there is no mammalian animal model of sMyBP-C, but new technologies including CRISPR/Cas9 and xenografting of human biopsies into immunodeficient mice could provide unique ways to study the regulation and roles of sMyBP-C in health and disease. PMID- 27683562 TI - A Descriptive Study of Feelings of Arrested Escape (Entrapment) and Arrested Anger in People Presenting to an Emergency Department Following an Episode of Self-Harm. AB - BACKGROUND AND OBJECTIVES: To explore the role of elevated feelings of anger and desires to escape (fight/flight), which are experienced as inhibited, blocked, and arrested (i.e., arrested anger and arrested flight/escape leading to feelings of entrapment). This descriptive study developed measures of arrested anger and arrested flight and explored these in the context of a recent self-harm event in people presenting to a Hospital's Emergency Department (ED). METHODS: Fifty-eight individuals presenting to an ED following an act of self-harm were recruited. Participants completed newly developed measures of arrested flight, arrested anger and anger with self in regard to self-harm, and suicide intent and depression. RESULTS: Ninety-three percent of participants presented after self poisoning. The majority (95%) reported having experienced high escape motivation that felt blocked (arrested flight) with 69% reporting feeling angry with someone but unable to express it (arrested anger). For many participants (53.7%), strong desires to escape from current situations and/or to express anger did not diminish immediately after the act. LIMITATIONS: As with many studies, a select group of participants agreed to take part and we did not keep records of how many refused. There are no other validated measures of arrested escape and arrested anger and so for this study, our short item-focused measures rely on face validity. CONCLUSION: Arrested defenses of fight and flight, and self-criticism are common in those who have self-harmed and may continue after acts of self harm. Many participants revealed that talking about their experiences of escape motivation and blocked anger (using our measures) was helpful to them. PRACTICE POINTS: Feelings of entrapment and arrested anger are common in people who self harmClinicians could benefit from increased awareness and measures of arrested flight and arrested angerDiscussing these concepts and experiences appears to be useful to people who have self-harmedFurther research is needed on how best to help people with such experiences. PMID- 27683564 TI - A Comprehensive Evaluation of a Lifelong Learning Program: Program 60. AB - Lifelong learning programs meet older adults' educational needs and further support their health and well-being leading to more successful aging. In particular, university-based lifelong learning programs have provided older adults with opportunities to not only develop skills and knowledge but also expand new social networks with people of different ages. This study evaluated a university-based lifelong learning program, Program 60, to identify the relationships between participants' experiences in the program and their quality of life. An online survey was employed, and 107 participants completed the self report survey. The participants reported that classes helped increase their emotional satisfaction and that they enjoyed taking classes with younger students. Their experiences in the program reliably predicted psychological and social elements of their quality of life ( p = .004 and p = .019, respectively). Study results provide helpful information for the development of lifelong learning programs that are responsive to the increasing demands of older adults. PMID- 27683565 TI - High-School Teachers' Beliefs about Effort and Their Attitudes toward Struggling and Smart Students in a Confucian Society. AB - Previous studies conducted in Western societies showed that instructors' beliefs about intellectual ability affected their attitudes toward students. However, in many East Asian societies influenced by Confucian culture, teachers not only hold beliefs of ability but also two kinds of beliefs about effort: obligation oriented belief (i.e., believing that effort-making is a student's role obligation) and improvement-oriented belief (i.e., believing that effort can conquer the limitations of one's ability). This study aimed to investigate the relationships between teachers' effort beliefs and their attitudes toward favoritism, praise, and expectations toward struggling and smart students. The participants were 151 Taiwanese high-school teachers. Results of Structure Equation Modeling showed that (1) teachers' obligation-oriented belief about effort was positively correlated with their favoritism, praise, short-term and long-term expectations of struggling students, but negatively correlated with their favoritism and praise of smart students, (2) teachers' improvement orientated belief about effort was negatively correlated with their short-term expectation of smart students and favoritism of struggling students, but positively correlated with their praise of smart students, and (3) the entity theory of intelligence was negatively correlated with favoritism and praise of struggling students, but positively correlated with favoritism of smart students. The theoretical and cultural implications are discussed. PMID- 27683563 TI - Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals. AB - Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes. PMID- 27683566 TI - Contribution of Visuospatial and Motion-Tracking to Invisible Motion. AB - People experience an object's motion even when it is occluded. We investigate the processing of invisible motion in three experiments. Observers saw a moving circle passing behind an invisible, irregular hendecagonal polygon and had to respond as quickly as possible when the target had "just reappeared" from behind the occluder. Without explicit cues allowing the end of each of the eight hidden trajectories to be predicted (length ranging between 4.7 and 5 deg), we found as expected, if visuospatial attention was involved, anticipation errors, providing that information on pre-occluder motion was available. This indicates that the observers, rather than simply responding when they saw the target, tended to anticipate its reappearance (Experiment 1). The new finding is that, with a fixation mark indicating the center of the invisible trajectory, a linear relationship between the physical and judged occlusion duration is found, but not without it (Experiment 2) or with a fixation mark varying in position from trial to trial (Experiment 3). We interpret the role of central fixation in the differences in distinguishing trajectories smaller than 0.3 deg, by suggesting that it reflects spatiotemporal computation and motion-tracking. These two mechanisms allow visual imagery to form of the point symmetrical to that of the disappearance, with respect to fixation, and then for the occluded moving target to be tracked up to this point. PMID- 27683567 TI - Emotion Regulation in Schema Therapy and Dialectical Behavior Therapy. AB - Schema therapy (ST) and dialectical behavior therapy (DBT) have both shown to be effective treatment methods especially for borderline personality disorder. Both, ST and DBT, have their roots in cognitive behavioral therapy and aim at helping patient to deal with emotional dysregulation. However, there are major differences in the terminology, explanatory models and techniques used in the both methods. This article gives an overview of the major therapeutic techniques used in ST and DBT with respect to emotion regulation and systematically puts them in the context of James Gross' process model of emotion regulation. Similarities and differences of the two methods are highlighted and illustrated with a case example. A core difference of the two approaches is that DBT directly focusses on the acquisition of emotion regulation skills, whereas ST does seldom address emotion regulation directly. All DBT-modules (mindfulness, distress tolerance, emotion regulation, interpersonal effectiveness) are intended to improve emotion regulation skills and patients are encouraged to train these skills on a regular basis. DBT assumes that improved skills and skills use will result in better emotion regulation. In ST problems in emotion regulation are seen as a consequence of adverse early experiences (e.g., lack of safe attachment, childhood abuse or emotional neglect). These negative experiences have led to unprocessed psychological traumas and fear of emotions and result in attempts to avoid emotions and dysfunctional meta-cognitive schemas about the meaning of emotions. ST assumes that when these underlying problems are addressed, emotion regulation improves. Major ST techniques for trauma processing, emotional avoidance and dysregulation are limited reparenting, empathic confrontation and experiential techniques like chair dialogs and imagery rescripting. PMID- 27683569 TI - Learning from the Past-The Need for Empirical Evidence on the Transfer Effects of Computer Programming Skills. PMID- 27683568 TI - Impaired Self-Monitoring of Inner Speech in Schizophrenia Patients with Verbal Hallucinations and in Non-clinical Individuals Prone to Hallucinations. AB - BACKGROUND: Previous research has shown that various memory errors reflecting failure in the self-monitoring of speech were associated with auditory/verbal hallucinations in schizophrenia patients and with proneness to hallucinations in non-clinical individuals. METHOD: We administered to 57 schizophrenia patients and 60 healthy participants a verbal memory task involving free recall and recognition of lists of words with different structures (high-frequency, low frequency, and semantically organisable words). Extra-list intrusions in free recall were tallied, and the response bias reflecting tendency to make false recognitions of non-presented words was computed for each list. RESULTS: In the male patient subsample, extra-list intrusions were positively associated with verbal hallucinations and inversely associated with negative symptoms. In the healthy participants the extra-list intrusions were positively associated with proneness to hallucinations. A liberal response bias in the recognition of the high-frequency words was associated with verbal hallucinations in male patients and with proneness to hallucinations in healthy men. Meanwhile, a conservative response bias for these high-frequency words was associated with negative symptoms in male patients and with social anhedonia in healthy men. CONCLUSION: Misattribution of inner speech to an external source, reflected by false recollection of familiar material, seems to underlie both clinical and non clinical hallucinations. Further, both clinical and non-clinical negative symptoms may exert on verbal memory errors an effect opposite to that of hallucinations. PMID- 27683570 TI - How Math Anxiety Relates to Number-Space Associations. AB - Given the considerable prevalence of math anxiety, it is important to identify the factors contributing to it in order to improve mathematical learning. Research on math anxiety typically focusses on the effects of more complex arithmetic skills. Recent evidence, however, suggests that deficits in basic numerical processing and spatial skills also constitute potential risk factors of math anxiety. Given these observations, we determined whether math anxiety also depends on the quality of spatial-numerical associations. Behavioral evidence for a tight link between numerical and spatial representations is given by the SNARC (spatial-numerical association of response codes) effect, characterized by faster left-/right-sided responses for small/large digits respectively in binary classification tasks. We compared the strength of the SNARC effect between high and low math anxious individuals using the classical parity judgment task in addition to evaluating their spatial skills, arithmetic performance, working memory and inhibitory control. Greater math anxiety was significantly associated with stronger spatio-numerical interactions. This finding adds to the recent evidence supporting a link between math anxiety and basic numerical abilities and strengthens the idea that certain characteristics of low-level number processing such as stronger number-space associations constitute a potential risk factor of math anxiety. PMID- 27683571 TI - Profiles of Perfectionism and School Anxiety: A Review of the 2 * 2 Model of Dispositional Perfectionism in Child Population. AB - The 2 * 2 model of dispositional perfectionism has been very well received by researchers of the topic, leading to the creation of new studies that have analyzed the way in which the four proposed subtypes are distinctly associated with measures of adaptation and maladjustment. The goal of this study was to determine the possible existence of four profiles of child perfectionism that are congruent with the subtypes proposed by the 2 * 2 model, and whether these subtypes are associated with school anxiety, in accordance with the hypotheses established by the model. The sample was composed of 2157 students from Spanish Primary Education aged between 8 and 11 years (M = 9.60, SD = 1.24). The Child and Adolescent Perfectionism Scale was used to assess Socially Prescribed Perfectionism and Self-Oriented Perfectionism, and the School Anxiety Inventory for Primary Education was used to measure school anxiety. The results of cluster analysis identified four differential groups of perfectionists similar to the subtypes defined by the 2 * 2 model: Non-Perfectionism, Pure Personal Standards Perfectionism (Pure PSP), Pure Evaluative Concerns Perfectionism (Pure ECP), and Mixed Perfectionism. The four groups presented a differentiable pattern of association with school anxiety, with the exception of Pure PSP and Pure ECP, which showed no significant differences. Participants classified as Non perfectionists presented the most adaptive outcomes, whereas subjects included in the Mixed Perfectionism group scored significantly higher on school anxiety than the three remaining groups. To conclude, the results partially supported the hypotheses of the 2 * 2 model, questioning the consideration of Self-Oriented Perfectionism as a positive manifestation of perfectionism and showing that it is the combination of high scores in both perfectionist dimensions, Self-Oriented Perfectionism and Socially Prescribed Perfectionism that implies higher levels of school anxiety. These findings should be taken into account when generalizing the 2 * 2 model to child population. PMID- 27683572 TI - Stress at School? A Qualitative Study on Illegitimate Tasks during Teacher Training. AB - What do I expect when stating that "I am going to be a teacher"? Social roles, including professional roles, often become part of people's identity and thus, of the self. As people typically strive for maintaining a positive sense of self, threats to one's role identity are likely to induce stress. In line with these considerations, Semmer et al. recently (e.g., Semmer et al., 2007, 2015) introduced "illegitimate tasks" as a new concept of stressors. Illegitimate tasks, which are defined as unnecessary or unreasonable tasks, threaten the self because they signal a lack of appreciation regarding one's professional role. Teacher training is a phase of role transition in which the occurrence of illegitimate tasks becomes likely. A holistic understanding of these tasks, however, has been missing up to now. Is there already a professional role identity during teacher training that is vulnerable to threats like the illegitimacy of tasks? What are typical illegitimate tasks in the context of teacher training? In order to close this research gap, 39 situations taken from 16 interviews with teaching trainees were analyzed in the present study on the basis of qualitative content analysis. Seminars and standing in to hold lessons for other teachers were identified as most prevalent illegitimate tasks. More specifically, unnecessary tasks could be classified as sub challenging, inefficient and lacking in organization (e.g., writing reports about workshops no one will ever read). Unreasonable tasks appeared overextending, fell outside responsibility, and lacked supervisory support. Training interventions focusing upon task design and supervisory behavior are suggested for improvement. PMID- 27683574 TI - Transcription Profiling Analysis of Mango-Fusarium mangiferae Interaction. AB - Malformation caused by Fusarium mangiferae is one of the most destructive mango diseases affecting the canopy and floral development, leading to dramatic reduction in fruit yield. To further understand the mechanism of interaction between mango and F. mangiferae, we monitored the transcriptome profiles of buds from susceptible mango plants, which were challenged with F. mangiferae. More than 99 million reads were deduced by RNA-sequencing and were assembled into 121,267 unigenes. Based on the sequence similarity searches, 61,706 unigenes were identified, of which 21,273 and 50,410 were assigned to gene ontology categories and clusters of orthologous groups, respectively, and 33,243 were mapped to 119 KEGG pathways. The differentially expressed genes of mango were detected, having 15,830, 26,061, and 20,146 DEGs respectively, after infection for 45, 75, and 120 days. The analysis of the comparative transcriptome suggests that basic defense mechanisms play important roles in disease resistance. The data also show the transcriptional responses of interactions between mango and the pathogen and more drastic changes in the host transcriptome in response to the pathogen. These results could be used to develop new methods to broaden the resistance of mango to malformation, including the over-expression of key mango genes. PMID- 27683573 TI - Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog. AB - While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270(T) and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidans (T), the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied. First, the effect on biofilm formation of a synthetic AHL tetrazolic analog, tetrazole 9c, known for its agonistic QS activity, was assessed by fluorescence and electron microscopy. A fast adherence of A. ferrooxidans (T) cells on sulfur coupons was observed. Then, tetrazole 9c was used in DNA microarray experiments that allowed the identification of genes regulated by quorum sensing signaling, and more particularly, those involved in early biofilm formation. Interestingly, afeI gene, encoding the AHL synthase, but not the A. ferrooxidans quorum sensing transcriptional regulator AfeR encoding gene, was shown to be regulated by quorum sensing. Data indicated that quorum sensing network represents at least 4.5% (141 genes) of the ATCC 23270(T) genome of which 42.5% (60 genes) are related to biofilm formation. Finally, AfeR was shown to bind specifically to the regulatory region of the afeI gene at the level of the palindromic sequence predicted to be the AfeR binding site. Our results give new insights on the response of A. ferrooxidans to quorum sensing and on biofilm biogenesis. PMID- 27683575 TI - Activation of Langerhans-Type Dendritic Cells Alters Human Cytomegalovirus Infection and Reactivation in a Stimulus-Dependent Manner. AB - Oral mucosal Langerhans cells (LC) are likely to play important roles in host defense against infection by human cytomegalovirus (CMV). We previously showed that in vitro-differentiated immature LC (iLC) populations contain smaller amounts of infected cells but produce higher yields than mature LC (mLC) cultures, obtained by iLC stimulation with fetal bovine serum (FBS), CD40 ligand (CD40L) and lipopolysaccharide (LPS). Here, we sought to determine if exposure to select stimuli can improve LC permissiveness to infection, if specific components of the mLC cocktail are responsible for lowering viral yields, if this is due to defects in progeny production or release, and if these restrictions are also effective against reactivated virus. None of the stimuli tested extended the proportion of infected cells to 100%, suggesting that the block to infection onset cannot be fully removed. While CD40L and FBS exerted positive effects on viral progeny production per cell, stimulation with LPS alone or in combination with CD40L was detrimental. Reductions in viral titers were not due to defects in progeny release, and the permissive or restrictive intracellular environment established upon exposure to each stimulus appeared to act in a somewhat similar way toward lytic and latent infections. PMID- 27683576 TI - Mineral vs. Organic Amendments: Microbial Community Structure, Activity and Abundance of Agriculturally Relevant Microbes Are Driven by Long-Term Fertilization Strategies. AB - Soil management is fundamental to all agricultural systems and fertilization practices have contributed substantially to the impressive increases in food production. Despite the pivotal role of soil microorganisms in agro-ecosystems, we still have a limited understanding of the complex response of the soil microbiota to organic and mineral fertilization in the very long-term. Here, we report the effects of different fertilization regimes (mineral, organic and combined mineral and organic fertilization), carried out for more than a century, on the structure and activity of the soil microbiome. Organic matter content, nutrient concentrations, and microbial biomass carbon were significantly increased by mineral, and even more strongly by organic fertilization. Pyrosequencing revealed significant differences between the structures of bacterial and fungal soil communities associated to each fertilization regime. Organic fertilization increased bacterial diversity, and stimulated microbial groups (Firmicutes, Proteobacteria, and Zygomycota) that are known to prefer nutrient-rich environments, and that are involved in the degradation of complex organic compounds. In contrast, soils not receiving manure harbored distinct microbial communities enriched in oligotrophic organisms adapted to nutrient limited environments, as Acidobacteria. The fertilization regime also affected the relative abundances of plant beneficial and detrimental microbial taxa, which may influence productivity and stability of the agroecosystem. As expected, the activity of microbial exoenzymes involved in carbon, nitrogen, and phosphorous mineralization were enhanced by both types of fertilization. However, in contrast to comparable studies, the highest chitinase and phosphatase activities were observed in the solely mineral fertilized soil. Interestingly, these two enzymes showed also a particular high biomass-specific activities and a strong negative relation with soil pH. As many soil parameters are known to change slowly, the particularity of unchanged fertilization treatments since 1902 allows a profound assessment of linkages between management and abiotic as well as biotic soil parameters. Our study revealed that pH and TOC were the majors, while nitrogen and phosphorous pools were minors, drivers for structure and activity of the soil microbial community. Due to the long-term treatments studied, our findings likely represent permanent and stable, rather than transient, responses of soil microbial communities to fertilization. PMID- 27683577 TI - Is Quorum Sensing Interference a Viable Alternative to Treat Pseudomonas aeruginosa Infections? AB - Quorum sensing (QS) coordinates the expression of multiple virulence factors in Pseudomonas aeruginosa; hence its inhibition has been postulated as a new alternative to treat its infections. In particular, QS interference approaches claim that they attenuate bacterial virulence without directly decreasing bacterial growth and suggest that in vivo the immune system would control the infections. Moreover, since in vitro experiments performed in rich medium demonstrate that interfering with QS decreases the production of virulence factors without affecting bacterial growth it was assumed than in vivo therapies will minimize the selection of resistant strains. Therefore, the underlying assumptions toward an effective implementation of a successful Quorum sensing interference (QSI) therapy for treating P. aeruginosa infections are that (i) QS only exerts important effects in the regulation of virulence genes but it does not affect metabolic processes linked to growth, (ii) the expression of virulence factors is only positively regulated by QS, (iii) inhibition of virulence factors in vivo do not affect bacterial growth, (iv) the immune system of the infected patients will be able to get rid of the infections, and (v) the therapy will be effective in the strains that are actively producing the infections. Nevertheless, for QSI in P. aeruginosa, substantial experimental evidence against the validity of most of these assumptions has accumulated during the past years, suggesting that a far better understanding of its virulence and its behavior during infections is needed in order to design truly solid QSI therapeutic alternatives to combat this remarkable pathogen. PMID- 27683578 TI - Features of Memory-Like and PD-1(+) Human NK Cell Subsets. AB - Human NK cells are distinguished into CD56(bright)CD16(-) cells and CD56(dim)CD16(+) cells. These two subsets are conventionally associated with differential functional outcomes and are heterogeneous with respect to the expression of KIR and CD94/NKG2 heterodimers that represent the two major types of HLA-class I-specific receptors. Recent studies indicated that immature CD56(bright) NK cells, homogeneously expressing the inhibitory CD94/NKG2A receptor, are precursors of CD56(dim) NK cells that, in turn, during their process of differentiation, lose expression of CD94/NKG2A and subsequentially acquire inhibitory KIRs and LIR-1. The terminally differentiated phenotype of CD56(dim) cells is marked by the expression of the CD57 molecule that is associated with poor responsiveness to cytokine stimulation, but retained cytolytic capacity. Remarkably, this NKG2A(-)KIR(+)LIR-1(+)CD57(+)CD56(dim) NK cell subset when derived from individuals previously exposed to pathogens, such as human cytomegalovirus (HCMV), may contain "memory-like" NK cells. These cells are generally characterized by an upregulation of the activating receptor CD94/NKG2C and a downregulation of the inhibitory receptor Siglec-7. The "memory like" NK cells are persistent over time and display some hallmarks of adaptive immunity, i.e., clonal expansion, more effective antitumor and antiviral immune responses, longevity, as well as given epigenetic modifications. Interestingly, unknown cofactors associated with HCMV infection may induce the onset of a recently identified fully mature NK cell subset, characterized by marked downregulation of the activating receptors NKp30 and NKp46 and by the unexpected expression of the inhibitory PD-1 receptor. This phenotype correlates with an impaired antitumor NK cell activity that can be partially restored by antibody mediated disruption of PD-1/PD-L interaction. PMID- 27683581 TI - Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. AB - The era of big data is coming, and evidence-based medicine is attracting increasing attention to improve decision making in medical practice via integrating evidence from well designed and conducted clinical research. Meta analysis is a statistical technique widely used in evidence-based medicine for analytically combining the findings from independent clinical trials to provide an overall estimation of a treatment effectiveness. The sample mean and standard deviation are two commonly used statistics in meta-analysis but some trials use the median, the minimum and maximum values, or sometimes the first and third quartiles to report the results. Thus, to pool results in a consistent format, researchers need to transform those information back to the sample mean and standard deviation. In this article, we investigate the optimal estimation of the sample mean for meta-analysis from both theoretical and empirical perspectives. A major drawback in the literature is that the sample size, needless to say its importance, is either ignored or used in a stepwise but somewhat arbitrary manner, e.g. the famous method proposed by Hozo et al. We solve this issue by incorporating the sample size in a smoothly changing weight in the estimators to reach the optimal estimation. Our proposed estimators not only improve the existing ones significantly but also share the same virtue of the simplicity. The real data application indicates that our proposed estimators are capable to serve as "rules of thumb" and will be widely applied in evidence-based medicine. PMID- 27683580 TI - Tr1-Like T Cells - An Enigmatic Regulatory T Cell Lineage. AB - The immune system evolved to respond to foreign invaders and prevent autoimmunity to self-antigens. Several types of regulatory T cells facilitate the latter process. These include a subset of Foxp3(-) CD4(+) T cells able to secrete IL-10 in an antigen-specific manner, type 1 regulatory (Tr1) T cells. Although their suppressive function has been confirmed both in vitro and in vivo, their phenotype remains poorly defined. It has been suggested that the surface markers LAG-3 and CD49b are biomarkers for murine and human Tr1 cells. Here, we discuss these findings in the context of our data regarding the expression pattern of inhibitory receptors (IRs) CD49b, TIM-3, PD-1, TIGIT, LAG-3, and ICOS on Tr1-like human T cells generated in vitro from CD4(+) memory T cells stimulated with alphaCD3 and alphaCD28 antibodies. We found that there were no differences in IR expression between IL-10(+) and IL-10(-) T cells. However, CD4(+)IL-10(+) T cells isolated ex vivo, following a short stimulation and cytokine secretion assay, contained significantly higher proportions of TIM-3(+) and PD-1(+) cells. They also expressed significantly higher TIGIT mRNA and showed a trend toward increased TIM-3 mRNA levels. These data led us to conclude that large pools of IRs may be stored intracellularly; hence, they may not represent ideal candidates as cell surface biomarkers for Tr1-like T cells. PMID- 27683582 TI - Floral Initiation in Response to Planting Date Reveals the Key Role of Floral Meristem Differentiation Prior to Budding in Canola (Brassica napus L.). AB - In Brassica napus, floral development is a decisive factor in silique formation, and it is influenced by many cultivation practices including planting date. However, the effect of planting date on floral initiation in canola is poorly understood at present. A field experiment was conducted using a split plot design, in which three planting dates (early, 15 September, middle, 1 October, and late, 15 October) served as main plot and five varieties differing in maturity (1358, J22, Zhongshuang 11, Zheshuang 8, and Zheyou 50) employed as subplot. The purpose of this study was to shed light on the process of floral meristem (FM) differentiation, the influence of planting date on growth period (GP) and floral initiation, and silique formation. The main stages of FM developments can be divided into four stages: first, the transition from shoot apical meristem to FM; second, flower initiation; third, gynoecium and androecium differentiation; and fourth, bud formation. Our results showed that all genotypes had increased GPs from sowing to FM differentiation as planting date was delayed while the GPs from FM differentiation to budding varied year by year except the very early variety, 1358. Based on the number of flowers present at the different reproductive stages, the flowers produced from FM differentiation to budding closely approximated the final silique even though the FM differentiated continuously after budding and peaked generally at the middle flowering stage. The ratio of siliques to maximum flower number ranged from 48 to 80%. These results suggest that (1) the period from FM differentiation to budding is vital for effective flower and silique formation although there was no significant correlation between the length of the period and effective flowers and siliques, and (2) the increased number of flowers from budding were generally ineffective. Therefore, maximizing flower numbers prior to budding will improve silique numbers, and reducing FM degeneration should also increase final silique formation. From the results of our study, we offer guidelines for planting canola varieties that differ in maturity in order to maximize effective flower numbers. PMID- 27683579 TI - T-Cell-Based Immunotherapy for Osteosarcoma: Challenges and Opportunities. AB - Even though combining surgery with chemotherapy has significantly improved the prognosis of osteosarcoma patients, advanced, metastatic, or recurrent osteosarcomas are often non-responsive to chemotherapy, making development of novel efficient therapeutic methods an urgent need. Adoptive immunotherapy has the potential to be a useful non-surgical modality for treatment of osteosarcoma. Recently, alternative strategies, including immunotherapies using naturally occurring or genetically modified T cells, have been found to hold promise in the treatment of hematologic malignancies and solid tumors. In this review, we will discuss possible T-cell-based therapies against osteosarcoma with a special emphasis on combination strategies to improve the effectiveness of adoptive T cell transfer and, thus, to provide a rationale for the clinical development of immunotherapies. PMID- 27683583 TI - Selenium Biofortification in Radish Enhances Nutritional Quality via Accumulation of Methyl-Selenocysteine and Promotion of Transcripts and Metabolites Related to Glucosinolates, Phenolics, and Amino Acids. AB - Two selenium (Se) fertilization methods were tested for their effects on levels of anticarcinogenic selenocompounds in radish (Raphanus sativus), as well as other nutraceuticals. First, radish was grown on soil and foliar selenate applied 7 days before harvest at 0, 5, 10, and 20 mg Se per plant. Selenium levels were up to 1200 mg Se/kg DW in leaves and 120 mg Se/kg DW in roots. The thiols cysteine and glutathione were present at 2-3-fold higher levels in roots of Se treated plants, and total glucosinolate levels were 35% higher, due to increases in glucoraphanin. The only seleno-aminoacid detected in Se treated plants was Se methyl-SeCys (100 mg/kg FW in leaves, 33 mg/kg FW in roots). The levels of phenolic aminoacids increased with selenate treatment, as did root total nitrogen and protein content, while the level of several polyphenols decreased. Second, radish was grown in hydroponics and supplied with 0, 5, 10, 20, or 40 MUM selenate for 1 week. Selenate treatment led to a 20-30% increase in biomass. Selenium concentration was 242 mg Se/kg DW in leaves and 85 mg Se/kg DW in roots. Cysteine levels decreased with Se in leaves but increased in roots; glutatione levels decreased in both. Total glucosinolate levels in leaves decreased with Se treatment due to repression of genes involved in glucosinolates metabolism. Se methyl-SeCys concentration ranged from 7-15 mg/kg FW. Aminoacid concentration increased with Se treatment in leaves but decreased in roots. Roots of Se treated plants contained elevated transcript levels of sulfate transporters (Sultr) and ATP sulfurylase, a key enzyme of S/Se assimilation. No effects on polyphenols were observed. In conclusion, Se biofortification of radish roots may be achieved via foliar spray or hydroponic supply. One to ten radishes could fulfill the daily human requirement (70 MUg) after a single foliar spray of 5 mg selenate per plant or 1 week of 5-10 MUM selenate supply in hydroponics. The radishes metabolized selenate to the anticarcinogenic compound Se-methyl-selenocysteine. Selenate treatment enhanced levels of other nutraceuticals in radish roots, including glucoraphanin. Therefore, Se biofortification can produce plants with superior health benefits. PMID- 27683585 TI - Prediction of Host-Derived miRNAs with the Potential to Target PVY in Potato Plants. AB - Potato virus Y has emerged as a threatening problem in all potato growing areas around the globe. PVY reduces the yield and quality of potato cultivars. During the last 30 years, significant genetic changes in PVY strains have been observed with an increased incidence associated with crop damage. In the current study, computational approaches were applied to predict Potato derived miRNA targets in the PVY genome. The PVY genome is approximately 9 thousand nucleotides, which transcribes the following 6 genes:CI, NIa, NIb-Pro, HC-Pro, CP, and VPg. A total of 343 mature miRNAs were retrieved from the miRBase database and were examined for their target sequences in PVY genes using the minimum free energy (mfe), minimum folding energy, sequence complementarity and mRNA-miRNA hybridization approaches. The identified potato miRNAs against viral mRNA targets have antiviral activities, leading to translational inhibition by mRNA cleavage and/or mRNA blockage. We found 86 miRNAs targeting the PVY genome at 151 different sites. Moreover, only 36 miRNAs potentially targeted the PVY genome at 101 loci. The CI gene of the PVY genome was targeted by 32 miRNAs followed by the complementarity of 26, 19, 18, 16, and 13 miRNAs. Most importantly, we found 5 miRNAs (miR160a-5p, miR7997b, miR166c-3p, miR399h, and miR5303d) that could target the CI, NIa, NIb-Pro, HC-Pro, CP, and VPg genes of PVY. The predicted miRNAs can be used for the development of PVY-resistant potato crops in the future. PMID- 27683584 TI - Proteomic Profiling of the Interactions of Cd/Zn in the Roots of Dwarf Polish Wheat (Triticum polonicum L.). AB - Cd and Zn have been shown to interact antagonistically or synergistically in various plants. In the present study of dwarf polish wheat (DPW)roots, Cd uptake was inhibited by Zn, and Zn uptake was inhibited by Cd, suggesting that Cd and Zn interact antagonistically in this plant. A study of proteomic changes showed that Cd, Zn, and Cd+Zn stresses altered the expression of 206, 303, and 190 proteins respectively. Among these, 53 proteins were altered significantly in response to all these stresses (Cd, Zn, and Cd+Zn), whereas 58, 131, and 47 proteins were altered in response to individual stresses (Cd, Zn, and Cd+Zn, respectively). Sixty-one differentially expressed proteins (DEPs) were induced in response to both Cd and Zn stresses; 33 proteins were induced in response to both Cd and Cd+Zn stresses; and 57 proteins were induced in response to both Zn and Cd+Zn stresses. These results indicate that Cd and Zn induce differential molecular responses, which result in differing interactions of Cd/Zn. A number of proteins that mainly participate in oxidation-reduction and GSH, SAM, and sucrose metabolisms were induced in response to Cd stress, but not Cd+Zn stress. This result indicates that these proteins participate in Zn inhibition of Cd uptake and ultimately cause Zn detoxification of Cd. Meanwhile, a number of proteins that mainly participate in sucrose and organic acid metabolisms and oxidation reduction were induced in response to Zn stress but not Cd+Zn stress. This result indicates that these proteins participate in Cd inhibition of Zn uptake and ultimately cause the Cd detoxification of Zn. Other proteins induced in response to Cd, Zn, or Cd+Zn stress, participate in ribosome biogenesis, DNA metabolism, and protein folding/modification and may also participate in the differential defense mechanisms. PMID- 27683586 TI - Mitochondrial ROS and the Effectors of the Intrinsic Apoptotic Pathway in Aging Cells: The Discerning Killers! AB - It has become clear that mitochondrial reactive oxygen species (mtROS) are not simply villains and mitochondria the hapless targets of their attacks. Rather, it appears that mitochondrial dysfunction itself and the signaling function of mtROS can have positive effects on lifespan, helping to extend longevity. If events in the mitochondria can lead to better cellular homeostasis and better survival of the organism in ways beyond providing ATP and biosynthetic products, we can conjecture that they act on other cellular components through appropriate signaling pathways. We describe recent advances in a variety of species which promoted our understanding of how changes of mtROS generation are part of a system of signaling pathways that emanate from the mitochondria to impact organism lifespan through global changes, including in transcriptional patterns. In unraveling this, many old players in cellular homeostasis were encountered. Among these, maybe most strikingly, is the intrinsic apoptotic signaling pathway, which is the conduit by which at least one class of mtROS exercise their actions in the nematode Caenorhabditis elegans. This is a pathway that normally contributes to organismal homeostasis by killing defective or otherwise unwanted cells, and whose various compounds have also been implicated in other cellular processes. However, it was a surprise that that appropriate activation of a cell killing pathway can in fact prolong the lifespan of the organism. In the soma of adult C. elegans, all cells are post-mitotic, like many of our neurons and possibly some of our immune cells. These cells cannot simply be killed and replaced when showing signs of dysfunction. Thus, we speculate that it is the ability of the apoptotic pathway to pull together information about the functional and structural integrity of different cellular compartments that is the key property for why this pathway is used to decide when to boost defensive and repair processes in irreplaceable cells. When this process is artificially stimulated in mutants with elevated mtROS generation or with drug treatments it leads to lifespan prolongations beyond the normal lifespan of the organism. PMID- 27683587 TI - Cyclophilin D Is Involved in the Regulation of Autophagy and Affects the Lifespan of P. anserina in Response to Mitochondrial Oxidative Stress. AB - The mitochondrial permeability transition pore plays a key role in programmed cell death and the induction of autophagy. Opening of the pore is regulated by the mitochondrial peptidyl prolyl-cis, trans-isomerase cyclophilin D (CYPD). Previously it was shown in the aging model organism Podospora anserina that PaCYPD abundance increases during aging and that PaCypD overexpressors are characterized by accelerated aging. Here, we describe a role of PaCYPD in the regulation of autophagy. We found that the accelerated aging phenotype observed in a strain overexpressing PaCypD is not metacaspase-dependent but is accompanied by an increase of general autophagy and mitophagy, the selective autophagic degradation of mitochondria. It thus is linked to what has been defined as "autophagic cell death" or "type II" programmed cell death. Moreover, we found that the previously demonstrated age-related induction of autophagy in wild-type aging depends on the presence of PaCYPD. Deletion of PaCypD leads to a decrease in autophagy in later stages of age and under paraquat-mediated oxidative stress. Finally, we report that PaCYPD is also required for mitohormesis, the beneficial effect of mild mitochondrial stress. Thus, PaCYPD plays a key role in the context dependent regulation of pathways leading to pro-survival and pro-death effects of autophagy. PMID- 27683588 TI - Aspirating and Nonaspirating Swallow Sounds in Children: A Pilot Study. AB - BACKGROUND: Cervical auscultation (CA) may be used to complement feeding/swallowing evaluations when assessing for aspiration. There are no published pediatric studies that compare the properties of sounds between aspirating and nonaspirating swallows. AIM: To establish acoustic and perceptual profiles of aspirating and nonaspirating swallow sounds and determine if a difference exists between these 2 swallowing types. METHODS: Aspiration sound clips were obtained from recordings using CA simultaneously undertaken with videofluoroscopic swallow study. Aspiration was determined using the Penetration Aspiration Scale. The presence of perceptual swallow/breath parameters was rated by 2 speech pathologists who were blinded to the type of swallow. Acoustic data between groups were compared using Mann Whitney U-tests, while perceptual differences were determined by a test of 2 proportions. Combinations of perceptual parameters of 50 swallows (27 aspiration, 23 no aspiration) from 47 children (57% male) were statistically analyzed using area under a receiver operating characteristic (aROC), sensitivity, specificity, and positive and negative predictive values to determine predictors of aspirating swallows. RESULTS: The combination of post-swallow presence of wet breathing and wheeze and absence of GRS and normal breathing was the best predictor of aspiration (aROC = 0.82, 95% CI, 0.70-0.94). There were no significant differences between these 2 swallow types for peak frequency, duration, and peak amplitude. CONCLUSION: Our pilot study has shown that certain characteristics of swallow obtained using CA may be useful in the prediction of aspiration. However, further research comparing the acoustic swallowing sound profiles of normal children to children with dysphagia (who are aspirating) on a larger scale is required. PMID- 27683590 TI - An Infertile Patient with Abnormal Thyroid-Stimulating Hormone. PMID- 27683591 TI - Commentary. PMID- 27683592 TI - Commentary. PMID- 27683593 TI - Correction. PMID- 27683594 TI - Increased C3 Acylcarnitine Concentration in a Newborn. PMID- 27683595 TI - Three Patients with an Unusual Pattern on Urine Immunofixation. PMID- 27683596 TI - An Abrupt Hepatitis B Seroconversion. PMID- 27683597 TI - Where Has All the Hemoblobin A1c Gone? PMID- 27683598 TI - Interpretation of Jo Ractliffe's Drying fish on the beach at Ilha in Pen and Ink. PMID- 27683589 TI - Less is more: Nutrient limitation induces cross-talk of nutrient sensing pathways with NAD+ homeostasis and contributes to longevity. AB - Nutrient sensing pathways and their regulation grant cells control over their metabolism and growth in response to changing nutrients. Factors that regulate nutrient sensing can also modulate longevity. Reduced activity of nutrient sensing pathways such as glucose-sensing PKA, nitrogen-sensing TOR and S6 kinase homolog Sch9 have been linked to increased life span in the yeast, Saccharomyces cerevisiae, and higher eukaryotes. Recently, reduced activity of amino acid sensing SPS pathway was also shown to increase yeast life span. Life span extension by reduced SPS activity requires enhanced NAD+ (nicotinamide adenine dinucleotide, oxidized form) and nicotinamide riboside (NR, a NAD+ precursor) homeostasis. Maintaining adequate NAD+ pools has been shown to play key roles in life span extension, but factors regulating NAD+ metabolism and homeostasis are not completely understood. Recently, NAD+ metabolism was also linked to the phosphate (Pi)-sensing PHO pathway in yeast. Canonical PHO activation requires Pi starvation. Interestingly, NAD+ depletion without Pi-starvation was sufficient to induce PHO activation, increasing NR production and mobilization. Moreover, SPS signaling appears to function in parallel with PHO signaling components to regulate NR/NAD+ homeostasis. These studies suggest that NAD+ metabolism is likely controlled by and/or coordinated with multiple nutrient sensing pathways. Indeed, cross-regulation of PHO, PKA, TOR and Sch9 pathways was reported to potentially affect NAD+ metabolism; though detailed mechanisms remain unclear. This review discusses yeast longevity-related nutrient sensing pathways and possible mechanisms of life span extension, regulation of NAD+ homeostasis, and cross-talk among nutrient sensing pathways and NAD+ homeostasis. PMID- 27683599 TI - Botanical Books, Taxonomy, and the Art of Georgia O'Keeffe. PMID- 27683601 TI - Why we should care about the mysteries of pulmonary hypertension. PMID- 27683600 TI - Molecular Imaging of Angiogenesis in Cardiac Regeneration. AB - PURPOSE OF REVIEW: Myocardial infarction (MI) leading to heart failure displays an important cause of death worldwide. Adequate restoration of blood flow to prevent this transition is a crucial factor to improve long-term morbidity and mortality. Novel regenerative therapies have been thoroughly investigated within the past decades. RECENT FINDINGS: Increased angiogenesis in infarcted myocardium has shown beneficial effects on the prognosis of MI; therefore, the proangiogenic capacity of currently tested treatments is of specific interest. Molecular imaging to visualize formation of new blood vessels in vivo displays a promising option to monitor proangiogenic effects of regenerative substances. SUMMARY: Based on encouraging results in preclinical models, molecular angiogenesis imaging has recently been applied in a small set of patients. This article reviews recent literature on noninvasive in vivo molecular imaging of angiogenesis after MI as an integral part of cardiac regeneration. PMID- 27683602 TI - Integration of complex data sources to provide biologic insight into pulmonary vascular disease (2015 Grover Conference Series). AB - The application of complex data sources to pulmonary vascular diseases is an emerging and promising area of investigation. The use of -omics platforms, in silico modeling of gene networks, and linkage of large human cohorts with DNA biobanks are beginning to bear biologic insight into pulmonary hypertension. These approaches to high-throughput molecular phenotyping offer the possibility of discovering new therapeutic targets and identifying variability in response to therapy that can be leveraged to improve clinical care. Optimizing the methods for analyzing complex data sources and accruing large, well-phenotyped human cohorts linked to biologic data remain significant challenges. Here, we discuss two specific types of complex data sources-gene regulatory networks and DNA linked electronic medical record cohorts-that illustrate the promise, challenges, and current limitations of these approaches to understanding and managing pulmonary vascular disease. PMID- 27683606 TI - A systematic review and meta-analysis of trials using statins in pulmonary arterial hypertension. AB - Statins improve pulmonary vascular remodeling and right ventricular hypertrophy in animal models of pulmonary arterial hypertension (PAH). However, clinical trials assessing the efficacy of statins in patients with PAH have reported mixed results. In this systematic review and meta-analysis, we assess the efficacy of statins in patients with PAH. We included randomized controlled clinical trials (RCTs) that evaluated the efficacy of statins in patients with PAH. Primary outcomes were mortality and change in 6-minute walk distance (6MWD). Data are presented as odds ratio (OR) and weighted mean difference (WMD), with 95% confidence intervals (CIs), for binary and continuous variables, respectively. We included 4 RCTs of high quality. The mean age of participants was 42 +/- 13 years, and 70% were women. The statins used were simvastatin at 40-80 mg in two trials, atorvastatin 10 mg in one trial, and rosuvastatin 10 mg in the other. In the pooled-data analysis, there was no statistically significant improvement in mortality (OR: 0.75 [95% CI: 0.32-1.74]), 6MWD (WMD: -9.27 [95% CI: -27.73 to 9.20]), or cardiac index (WMD: 0.11 [95% CI: -0.04 to 0.27]) with statin therapy when compared to placebo. There was no difference in adverse events leading to withdrawal of therapy between statin and placebo groups. These data suggest that statins are not beneficial in the treatment of PAH. There is a need for large, well-conducted clinical trials assessing the effects of statins in patients with PAH. Future trials should include homogeneous patient populations and should be long-term, event-driven trials with combined morbidity and mortality end points. PMID- 27683604 TI - The emerging role of epigenetics in pulmonary arterial hypertension: an important avenue for clinical trials (2015 Grover Conference Series). AB - Epigenetics is an emerging field of research and clinical trials in cancer therapy that also has applications for pulmonary arterial hypertension (PAH), as there is evidence that epigenetic control of gene expression plays a significant role in PAH. The three types of epigenetic modification include DNA methylation, histone modification, and RNA interference. All three have been shown to be involved in the development of PAH. Currently, the enzymes that perform these modifications are the primary targets of neoplastic therapy. These targets are starting to be explored for therapies in PAH, mostly in animal models. In this review we summarize the basics of each type of epigenetic modification and the known sites and molecules involved in PAH, as well as current targets and prospects for clinical trials. PMID- 27683603 TI - Role of oxidized lipids in pulmonary arterial hypertension. AB - Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID- 27683605 TI - Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series). AB - The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16alpha-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin's effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer like phenotype are being explored. Extracellular signal-regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype. PMID- 27683607 TI - Clinical classification in pediatric pulmonary arterial hypertension associated with congenital heart disease. AB - Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore whether this classification accurately reflects patient/disease characteristics and survival. All children with CHD from a contemporary cohort of consecutive pediatric PAH patients followed in three major referral centers (Denver, New York, the Netherlands) were characterized and classified on the basis of the latest proposed clinical classification for PAH-CHD (World Symposium on Pulmonary Hypertension, Nice, 2013). According to this classification, 24% of 134 children were classified into group 1, 14% into group 2, 19% into group 3, and 30% into group 4; 11% could not be classified. Types of CHD and hemodynamic profile differed between groups, with the highest right atrial pressure in group 4 (P < 0.040). Group 3 children had Down syndrome less frequently (P = 0.011) but other (un)defined syndromes most frequently (P = 0.063) and received most intense PAH targeted therapy (P = 0.003). With 15 deaths and one lung transplant (12%; median follow-up: 4.3 years), survival differences could not be demonstrated between the groups in the Nice CHD classification. Pediatric PAH-CHD is a heterogeneous condition frequently associated with extracardiac, developmental factors that are believed to affect disease development. The Nice CHD classification identifies groups with specific patient/disease characteristics. However, a substantial proportion of children could not be classified. Group 3 forms a distinct disease entity. Its prognostic value could not be determined because of the low number of events. The Nice CHD classification supports clinical characterization of PAH CHD; however, further refinement is needed to classify all children with PAH-CHD. PMID- 27683609 TI - Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension. AB - Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects. PMID- 27683608 TI - Hemodynamic evidence of vascular remodeling in combined post- and precapillary pulmonary hypertension. AB - Although commonly encountered, patients with combined postcapillary and precapillary pulmonary hypertension (Cpc-PH) have poorly understood pulmonary vascular properties. The product of pulmonary vascular resistance and compliance, resistance-compliance (RC) time, is a measure of pulmonary vascular physiology. While RC time is lower in postcapillary PH than in precapillary PH, the RC time in Cpc-PH and the effect of pulmonary wedge pressure (PWP) on RC time are unknown. We tested the hypothesis that Cpc-PH has an RC time that resembles that in pulmonary arterial hypertension (PAH) more than that in isolated postcapillary PH (Ipc-PH). We analyzed the hemodynamics of 282 consecutive patients with PH referred for right heart catheterization (RHC) with a fluid challenge from 2004 to 2013 (cohort A) and 4,382 patients who underwent RHC between 1998 and 2014 for validation (cohort B). Baseline RC time in Cpc-PH was higher than that in Ipc-PH and lower than that in PAH in both cohorts (P < 0.001). In cohort A, RC time decreased after fluid challenge in patients with Ipc-PH but not in those with PAH or Cpc-PH (P < 0.001). In cohort B, the inverse relationship of pulmonary vascular compliance and resistance, as well as that of RC time and PWP, in Cpc-PH was similar to that in PAH and distinct from that in Ipc-PH. Our findings demonstrate that patients with Cpc-PH have pulmonary vascular physiology that resembles that of patients with PAH more than that of Ipc-PH patients. Further study is warranted to identify determinants of vascular remodeling and assess therapeutic response in this subset of PH. PMID- 27683610 TI - An observational study of inhaled-treprostinil respiratory-related safety in patients with pulmonary arterial hypertension. AB - Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory-related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory-related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)-approved PAH therapies. This was a long-term, prospective, observational study. All respiratory-related AEs were recorded during the study. The number of PAH patients enrolled was 1,333, 666 treated with inhaled treprostinil and 667 controls (treated with an FDA-approved PAH therapy other than inhaled treprostinil), for a total of 958 and 1,094 patient-years of exposure, respectively. In the inhaled-treprostinil group, 1,281 respiratory-related AEs were reported in 403 patients (61%), and in the control group, 1,295 respiratory related AEs were reported in 388 patients (58%). Cough, throat irritation, nasal discomfort, and hemoptysis were the most common respiratory-related AEs (occurring in >=2% of patients in either treatment group) that demonstrated a higher number of events per patient-year of exposure in the inhaled-treprostinil group than in the control group (risk ratio [95% confidence interval]: 1.487 [1.172-1.887], 3.777 [2.050-6.956], 2.039 [1.072-3.879], and 1.957 [1.024-3.741], respectively). Overall, inhaled treprostinil was well tolerated by PAH patients in routine clinical care, with respiratory-related AEs consistent with the known safety profile (trial registration: clinicaltrials.gov identifier: NCT01266265). PMID- 27683611 TI - An international physician survey of pulmonary arterial hypertension management. AB - We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients' New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%-21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID- 27683612 TI - Versican accumulates in vascular lesions in pulmonary arterial hypertension. AB - Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [(35)S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID- 27683615 TI - Pregnancy as a possible trigger for heritable pulmonary arterial hypertension. AB - It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID- 27683613 TI - Cyp2c44 gene disruption exacerbated pulmonary hypertension and heart failure in female but not male mice. AB - Epoxyeicosatrienoicacids (EETs), synthesized from arachidonic acid by epoxygenases of the CYP2C and CYP2J gene subfamilies, contribute to hypoxic pulmonary vasoconstriction (HPV) in mice. Despite their roles in HPV, it is controversial whether EETs mediate or ameliorate pulmonary hypertension (PH). A recent study showed that deficiency of Cyp2j did not protect male and female mice from hypoxia-induced PH. Since CYP2C44 is a functionally important epoxygenase, we hypothesized that knockout of the Cyp2c44 gene would protect both sexes of mice from hypoxia-induced PH. We tested this hypothesis in wild-type (WT) and Cyp2c44 knockout (Cyp2c44 (-/-)) mice exposed to normoxia (room air) and hypoxia (10% O2) for 5 weeks. Exposure of WT and Cyp2c44 (-/-) mice to hypoxia resulted in pulmonary vascular remodeling, increased pulmonary artery resistance, and decreased cardiac function in both sexes. However, in female Cyp2c44 (-/-) mice, compared with WT mice, (1) pulmonary artery resistance and right ventricular hypertrophy were greater, (2) cardiac index was lower, (3) left ventricular and arterial stiffness were higher, and (4) plasma aldosterone levels were higher, but (5) there was no difference in levels of EET in lungs and heart. Paradoxically and unexpectedly, we found that Cyp2c44 disruption exacerbated hypoxia-induced PH in female but not male mice. We attribute exacerbated PH in female Cyp2c44 (-/-) mice to elevated aldosterone and as-yet-unknown systemic factors. Therefore, we suggest a role for the human CYP2C genes in protecting women from severe PH and that this could be one of the underlying causes for a better 5-year survival rate in women than in men. PMID- 27683616 TI - Chronic thromboembolic pulmonary hypertension, pregnancy, and a pulmonary endarterectomy: a rare challenge. AB - It is well described that patients with group 1 forms of pulmonary arterial hypertension have a high risk of mortality during pregnancy and in the early postpartum period. However, to the authors' knowledge, the diagnosis and management of group 4 pulmonary hypertension due to chronic thromboembolic pulmonary hypertension (CTEPH) during pregnancy with early postpartum pulmonary endarterectomy (PEA) has not been previously reported. We report the case of a 28 year-old woman who received a diagnosis of CTEPH during her pregnancy, was managed as an inpatient by a multidisciplinary team throughout the pregnancy and early postpartum period, and underwent PEA 6 weeks after delivery. While the management of acute pulmonary embolus in pregnancy is well described, this unique case of CTEPH diagnosed during pregnancy illustrates several challenging management issues. PMID- 27683614 TI - Sphingosine-1-phosphate is involved in the occlusive arteriopathy of pulmonary arterial hypertension. AB - Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH. To test this hypothesis, we used plasma samples and lung tissue from patients with idiopathic PAH (IPAH) and the Sugen5416/hypoxia/normoxia rat model of occlusive PAH. Our study revealed an increase in the plasma concentration of S1P in patients with IPAH and in early and late stages of PAH in rats. We observed increased expression of both SphK1 and SphK2 in the remodeled pulmonary arteries of patients with IPAH and PAH rats. Exogenous S1P stimulated the proliferation of cultured rat pulmonary arterial endothelial and smooth-muscle cells. We also found that 3 weeks of treatment of late-stage PAH rats with an SphK1 inhibitor reduced the increased plasma levels of S1P and the occlusive pulmonary arteriopathy. Although inhibition of SphK1 improved cardiac index and the total pulmonary artery resistance index, it did not reduce right ventricular systolic pressure or right ventricular hypertrophy. Our study supports that S1P is involved in the pathogenesis of occlusive arteriopathy in PAH and provides further evidence that S1P signaling may be a novel therapeutic target. PMID- 27683618 TI - Postural tachycardia syndrome is not caused by deconditioning. PMID- 27683617 TI - NADPH oxidase 4 is not involved in hypoxia-induced pulmonary hypertension. PMID- 27683621 TI - Myocardial Mitochondria at the Intersection of Health and Disease. PMID- 27683622 TI - Chorioamniotic Separation Found on Obstetric Ultrasound and Perinatal Outcome. AB - Objective This study aims to evaluate pregnancy outcomes in patients with spontaneous and iatrogenic chorioamniotic separation diagnosed by ultrasound after 17 weeks. Methods This is a retrospective cohort study of women with a singleton pregnancy who were diagnosed with chorioamniotic separation (n = 106) after 17 weeks' gestation from January 2000 to January 2013. Patients with chorioamniotic separation were compared with a group of patients who had obstetric ultrasounds without a diagnosis of chorioamniotic separation. Those without chorioamniotic separation were matched (1:1) on gestational age on the date of the ultrasound ( +/- 2 weeks) (n = 106). The primary outcome was preterm delivery (< 37 weeks). Secondary outcomes included intrauterine growth restriction, stillbirth, and neonatal morbidity. Results The rate of preterm delivery was significantly higher for those with chorioamniotic separation than for those without (57.5 vs. 17.1%, p < 0.0001). There were no significant differences in the rate of aneuploidy, intrauterine growth restriction, stillbirth, or neonatal demise. The rate of stillbirth was significantly higher among those with chorioamniotic separation diagnosed before 24 weeks as compared with those diagnosed after 24 weeks (9.7 vs. 0%, p = 0.03). Conclusions Chorioamniotic separation is associated with preterm delivery. If diagnosed before 24 weeks, the rate of stillbirth is significantly higher. PMID- 27683623 TI - Differences between Men and Women Enrolling in Smoking Cessation Programs Using Yoga as a Complementary Therapy. AB - This study compares the characteristics of men and women, respectively, participating in two randomized controlled pilot studies whose primary aims were to test the feasibility of yoga as a complementary therapy for smoking cessation. Participants were aged 18-65, generally healthy and were daily smokers. Analysis of variance (ANOVA) and chi-square tests examined gender differences in smoking rate, potential treatment mediators, and covariates (e.g., smoking history, health status, weight concerns, mood, and prior withdrawal symptoms). A total of 55 women and 38 men participated in the study. Differences between men and women at enrollment included: women reported significantly greater withdrawal (p<0.005), anxiety (p=0.032), and depression (p=0.027) symptoms than men. More women than men (91% vs. 66%) reported having been told by their doctor to quit smoking (p=0.003), had an existing smoking-related illness (33% vs. 13%; p=0.032), and reported smoking for weight control (15% vs. 0%; p=0.014). Results showed good feasibility for recruiting both men and women into a study using yoga as a complementary therapy for smoking cessation. Results also indicate that interventions may need to be tailored to meet different needs (e.g., addressing co-morbid depression) between men and women. PMID- 27683624 TI - Cell Phone Use and Child and Adolescent Reading Proficiency. AB - This study examined the association between cell phone use, including minutes spent talking and number of text messages sent, and two measures of children's reading proficiency - tests of word decoding and reading comprehension - in the United States. Data were drawn from the Child Development Supplement to the Panel Study of Income Dynamics, a nationally representative survey of 1,147 children 10 18 in 2009. Children whose parents were better educated, who had higher family incomes, who had fewer siblings, and who lived in urban areas were more likely to own or share a cell phone. Among those with access to a phone, children who spent more time talking on the phone were less proficient at word decoding, whereas children who spent more time sending text messages had greater reading comprehension. Although girls spent more time texting than did boys, there were no gender differences in the association between time spent talking or number of text messages sent with achievement. In spite of racial/ethnic differences in cell phone use levels, there were no racial/ethnic differences in the association between cell phone use and reading proficiency. PMID- 27683620 TI - BSN723T Prevents Atherosclerosis and Weight Gain in ApoE Knockout Mice Fed a Western Diet. AB - OBJECTIVE: This study tests the hypothesis that BSN723T can prevent the development of hyperlipidemia and atherosclerosis in ApoE-/- knockout mice fed a Western (high fat, high cholesterol, and high sucrose) diet. BSN723T is a combination drug therapy consisting of D-tagatose and dihydromyricetin (BSN723). BACKGROUND: D-tagatose has an antihyperglycemic effect in animal and human studies and shows promise as a treatment for type 2 diabetes and obesity. Many claims regarding BSN723's pharmacological activities have been made including anti-cancer, anti-diabetic, anti-hypertensive, anti-inflammatory, and anti atherosclerotic effects. To our knowledge this is the first study that combines D tagatose and BSN723 for the treatment of hyperlipidemia and the prevention of atherosclerosis. METHODS: ApoE-deficient mice were randomized into five groups with equivalent mean body weights. The mice were given the following diets for 8 weeks: Group 1 - Standard diet; Group 2 - Western diet; Group 3 - Western diet formulated with D-tagatose; Group 4 - Western diet formulated with BSN723; Group 5 - Western diet formulated with BSN723T. Mice were measured for weight gain, tissue and organ weights, total serum cholesterol and triglycerides and formation of atherosclerosis. RESULTS: The addition of D-tagatose, either alone or in combination with BSN723, prevented the increase in adipose tissue and weight gain brought on by the Western diet. Both D-tagatose and BSN723 alone reduced total cholesterol and the formation of atherosclerosis in the aorta compared to mice on the Western diet. Addition of BSN723 to D-tagatose (BSN723T) did not increase efficacy in prevention of increases in cholesterol or atherosclerosis compared to D-tagatose alone. CONCLUSION: Addition of either D-tagatose or BSN723 alone to a Western diet prevented weight gain, increases in total serum cholesterol and triglycerides, and the formation of atherosclerosis. However, there was no additive or synergistic effect on the measured parameters with the combination BSN723T treatment. PMID- 27683619 TI - The Contrary Impact Of Diabetes And Exercise On Endothelial Nitric Oxide Synthase Function. PMID- 27683626 TI - Deceased organ donation for transplantation: Challenges and opportunities. AB - Organ transplantation saves thousands of lives every year but the shortage of donors is a major limiting factor to increase transplantation rates. To allow more patients to be transplanted before they die on the wait-list an increase in the number of donors is necessary. Patients with devastating irreversible brain injury, if medically suitable, are potential deceased donors and strategies are needed to successfully convert them into actual donors. Multiple steps in the process of deceased organ donation can be targeted to increase the number of organs suitable for transplant. In this review, after describing this process, we discuss current challenges and potential strategies to expand the pool of deceased donors. PMID- 27683625 TI - Association of Increasing GFR with Change in Albuminuria in the General Population. AB - BACKGROUND AND OBJECTIVES: Hyperfiltration at the single-nephron level has been proposed as an early stage of kidney dysfunction of different origins. Evidence supporting this hypothesis in humans is lacking, because there is no method of measuring single-nephron GFR in humans. However, increased whole-kidney GFR in the same individual implies an increased single-nephron GFR, because the number of nephrons does not increase with age. We hypothesized that an increase in GFR would be associated with an increased albumin-to-creatinine ratio in a cohort of the general population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured GFR by iohexol clearance at baseline in 2007-2009 and follow-up after 5.6 years in a representative sample of 1246 persons (aged 50-62 years) who were nondiabetic from the general population of Tromso, northern Norway. Participants were without cardiovascular disease, kidney disease, or diabetes at baseline. We investigated the association between change in GFR and change in albumin-to creatinine ratio. Increased GFR was defined as a positive change in GFR (change in GFR>0 ml/min) from baseline to follow-up. An albumin-to-creatinine ratio >30 mg/g was classified as albuminuria. RESULTS: Change in GFR was positively associated with a change in albumin-to-creatinine ratio in the entire cohort in the multiple linear regression. The albumin-to-creatinine ratiofollow-up-to albumin-to-creatinine ratiobaseline ratio increased by 8.0% (95% confidence interval, 1.4 to 15.0) per SD increase in change in GFR. When participants with increased GFR (n=343) were compared with those with a reduced GFR (n=903), the ratio increased by 16.3% (95% confidence interval, 1.1 to 33.7). The multivariable adjusted odds ratio for incident albuminuria (n=14) was 4.98 (95% confidence interval, 1.49 to 16.13) for those with an increased GFR (yes/no). CONCLUSIONS: Increasing GFR is associated with an increase in albumin-to creatinine ratio and incident albuminuria in the general nondiabetic population. These findings support single-nephron hyperfiltration as a risk factor for albuminuria in the general population. PMID- 27683627 TI - Cryptosporidium infection in solid organ transplantation. AB - Diarrhea is a common complication in solid organ transplant (SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population. PMID- 27683629 TI - Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders. AB - Post-transplant lymphoproliferative disorder (PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma (PT-DLBCL), Burkitt lymphoma (PT-BL) and plasmablastic lymphoma (PT-PBL) occur most frequently. However, in many studies various EBV(+) and EBV(-) PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials. PMID- 27683632 TI - Hemodynamic monitoring in heart failure and pulmonary hypertension: From analog tracings to the digital age. AB - Hemodynamic monitoring has long formed the cornerstone of heart failure (HF) and pulmonary hypertension diagnosis and management. We review the long history of invasive hemodynamic monitors initially using pulmonary artery (PA) pressure catheters in the hospital setting, to evaluating the utility of a number of implantable devices that can allow for ambulatory determination of intracardiac pressures. Although the use of indwelling PA catheters has fallen out of favor in a number of settings, implantable devices have afforded clinicians an opportunity for objective determination of a patient's volume status and pulmonary pressures. Some devices, such as the CardioMEMS and thoracic impedance monitors present as part of implantable cardiac defibrillators, are supported by a body of evidence which show the potential to reduce HF related morbidity and have received regulatory approval, whereas other devices have failed to show benefit and, in some cases, harm. Clearly these devices can convey a considerable amount of information and clinicians should start to familiarize themselves with their use and expect further development and refinement in the future. PMID- 27683631 TI - Genetic barriers in transplantation medicine. AB - The successful of transplantation is determined by the shared human leukocyte antigens (HLAs) and ABO blood group antigens between donor and recipient. In recent years, killer cell receptor [i.e., killer cell immunoglobulin-like receptor (KIR)] and major histocompatibility complex (MHC) class I chain-related gene molecule (i.e., MICA) were also reported as important determinants of transplant compatibility. At present, several different genotyping techniques (e.g., sequence specific primer and sequence based typing) can be used to characterize blood group, HLA, MICA and KIR and loci. These molecular techniques have several advantages because they do not depend on the availability of anti sera, cellular expression and have greater specificity and accuracy compared with the antibody-antigen based typing. Nonetheless, these molecular techniques have limited capability to capture increasing number of markers which have been demonstrated to determine donor and recipient compatibility. It is now possible to genotype multiple markers and to the extent of a complete sequencing of the human genome using next generation sequencer (NGS). This high throughput genotyping platform has been tested for HLA, and it is expected that NGS will be used to simultaneously genotype a large number of clinically relevant transplantation genes in near future. This is not far from reality due to the bioinformatics support given by the immunogenetics community and the rigorous improvement in NGS methodology. In addition, new developments in immune tolerance based therapy, donor recruitment strategies and bioengineering are expected to provide significant advances in the field of transplantation medicine. PMID- 27683630 TI - Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach. AB - Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID- 27683633 TI - Current techniques for AB0-incompatible living donor liver transplantation. AB - For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients' graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0i LDLT is a feasible option today and almost free of severe complications. PMID- 27683634 TI - Tregs and kidney: From diabetic nephropathy to renal transplantation. AB - Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs. PMID- 27683635 TI - Updates on antibody-mediated rejection in intestinal transplantation. AB - Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation. PMID- 27683636 TI - Pharmacological Tie2 activation in kidney transplantation. AB - AIM: To investigate the therapeutic potential of vasculotide (VT) - a Tie2 activating therapeutic - in kidney transplantation. METHODS: We performed a murine MHC-mismatched renal transplant model (C57Bl/6 male into Balb/c female) with 60 min cold and 30 min warm ischemia time. 500 ng VT was administered i.p. to donor mice 1 h before organ removal. In addition, recipients received 500 ng VT i.p. directly and 3 d after surgery. Survival was monitored and remaining animals were sacrificed 28 d after transplantation. In this model, we analyzed: (1) organ function; (2) Kaplan-Meier survival; (3) organ damage (periodic acid Schiff staining) via semi-quantitative scoring [0-4 (0 = no injury/inflammation to 4 = very severe injury/inflammation)]; (4) expression of renal endothelial adhesion molecules (ICAM-1) via immunofluorescence (IF) staining, immunoblotting and qPCR; (5) infiltration of inflammatory cells (IF Gr-1, F4/80); and (6) fibrosis via staining of alpha-smooth muscle actin (alphaSMA), Sirius red staining and immunoblotting of SMAD3 activation. RESULTS: Exogenous activation of Tie2 with VT resulted in diminished expression of peritubular and glomerular endothelial adhesion molecules. Consequently, infiltration of inflammatory cells (analyzed as ICAM-1, Gr-1 and F4/80 positive cells) was reduced in VT-treated mice compared to controls. Additionally, VT was protective against fibrogenesis after kidney transplantation. Trends towards lower serum creatinine (vehicle: 142 +/- 17 MUmol/L vs VT: 94 +/- 23 MUmol/L), urea (vehicle: 76 +/- 5 mmol/L vs VT: 60 +/- 8 mmol/L) and lactate dehydrogenase (vehicle: 1288 +/- 383 iU vs VT: 870 +/- 275 iU) were observed on day 6 after transplantation. Kaplan-Meier survival analysis showed improved survival rates in the VT-treated mice that did not reach statistical significance (27% vs 54%, P = 0.24, n = 11 per group). Exogenous activation of Tie2 via VT might reduce infiltration of inflammatory cells into renal tissue thereby protecting the transplant from early graft dysfunction potentially affecting long-term function. CONCLUSION: Protection of the endothelial microvasculature via the Tie2 axis in the early transplant setting might hold promise as a therapeutic target. PMID- 27683638 TI - Underutilization of palliative care services in the liver transplant population. AB - AIM: To evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant. METHODS: Evaluated were end stage liver disease patients who were removed from the liver transplant wait-list or died prior to transplant at a single transplant center over a 2-year period. Those who were removed due to noncompliance or ultimately transplanted elsewhere were excluded from this study. Patient characteristics associated with palliative care consultation were assessed using logistic regression analysis. RESULTS: Six hundred and eighty-three patients were listed for liver transplant in 2013-2014 with 107 (16%) dying (n = 62) or removed for clinical decompensation prior to liver transplant (n = 45): Median age was 58 years, and the majority were male (66%), Caucasian (53%), had Child C cirrhosis (61%) or hepatocellular carcinoma (52%). The palliative care team was consulted in only 18 of the 107 patients (17%) who died or were removed, 89% of which occurred as inpatients. Half of these consultations occurred within 72 h of death. In univariable analysis, patients of younger age, white race, and higher end-stage liver disease scores at time of listing and delisting were more likely to receive palliative care services. Only younger age [Odds ratio (OR) = 0.92; P = 0.02] and Caucasian race (OR = 4.90; P = 0.02) were still associated with integration of palliative care services through multivariable analysis. CONCLUSION: Palliative care services are grossly underutilized in older, non-white patients with cirrhosis on the liver transplant wait-list. We encourage early integration of these services into clinical decision-making in the transplant population, with further studies aimed at understanding barriers to consultation. PMID- 27683637 TI - Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation. AB - AIM: To describe the thromboelastography (TEG) "reference" values within a population of liver transplant (LT) candidates that underline the differences from healthy patients. METHODS: Between 2000 and 2013, 261 liver transplant patients with a model for end-stage liver disease (MELD) score between 15 and 40 were studied. In particular the adult patients (aged 18-70 years) underwent to a first LT with a MELD score between 15 and 40 were included, while all patients with acute liver failure, congenital bleeding disorders, and anticoagulant and/or antiplatelet drug use were excluded. In this population of cirrhotic patients, preoperative haematological and coagulation laboratory tests were collected, and the pretransplant thromboelastographic parameters were studied and compared with the parameters measured in a previously studied population of 40 healthy subjects. The basal TEG parameters analysed in the cirrhotic population of liver candidates were as follows: Reaction time (r), coagulation time (k), Angle-Rate of polymerization of clot (alpha Angle), Maximum strenght of clot (MA), Amplitudes of the TEG tracing at 30 min and 60 min after MA is measured (A30 and A60), and Fibrinolysis at 30 and 60 min after MA (Ly30 and Ly60). The possible correlation between the distribution of the reference range and the gender, age, MELD score (higher or lower than 20) and indications for transplantation (liver pathology) were also investigated. In particular, a MELD cut-off value of 20 was chosen to verify the possible correlation between the thromboelastographic reference range and MELD score. RESULTS: Most of the TEG reference values from patients with end-stage liver disease were significantly different from those measured in the healthy population and were outside the suggested normal ranges in up to 79.3% of subjects. Wide differences were found among all TEG variables, including r (41.5% of the values), k (48.6%), alpha (43.7%), MA (79.3%), A30 (74.4%) and A60 (80.9%), indicating a prevailing trend to hypocoagulability. The differences between the mean TEG values obtained from healthy subjects and the cirrhotic population were statistically significant for r (P = 0.039), k (P < 0.001), MA (P < 0.001), A30 (P < 0.001), A60 (P < 0.001) and Ly60 (P = 0.038), indicating slower and less stable clot formation in the cirrhotic patients. In the cirrhotic population, 9.5% of patients had an r value shorter than normal, indicating a tendency for faster clot formation. Within the cirrhotic patient population, gender, age and the presence of hepatocellular carcinoma or alcoholic cirrhosis were not significantly associated with greater clot firmness or enhanced whole blood clot formation, whereas greater clot strength was associated with a MELD score < 20, hepatitis C virus and cholestatic-related cirrhosis (P < 0.001; P = 0.013; P < 0.001). CONCLUSION: The range and distribution of TEG values in cirrhotic patients differ from those of healthy subjects, suggesting that a specific thromboelastographic reference range is required for liver transplant candidates. PMID- 27683639 TI - Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era? AB - AIM: To characterize major determinants of 20-year survival after liver transplantation (LT). METHODS: This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease (labMELD)-score and the Eurotransplant Donor Risk Index (ET-DRI) to unravel their impact on 20-year survival after LT. RESULTS: Twenty-year survivors were significantly younger (44 vs 50 years, P = 0.001), more likely to be female (49% vs 36%, P = 0.03) and less likely to be obese at the time of LT (19% vs 32%, P = 0.011). Mean labMELD-score (P = 0.156), rate of high-urgency LT (P = 0.210), cold-ischemia time (P = 0.994), rate of retransplantation (P = 0.12) and average donor age (28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors (P = 0.007). ET-DRI > 1.4 (P = 0.020) and donor age >= 30 years (P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labMELD-score categories (P = 0.263). CONCLUSION: LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs. PMID- 27683640 TI - Incidence and Risk Factors of Hypomagnesemia in Head and Neck Cancer Patients Treated with Cetuximab. AB - BACKGROUND: Hypomagnesemia is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the incidence and risk factors of hypomagnesemia in head and neck cancer patients treated with Cmab. METHODS: We retrospectively reviewed 131 head and neck cancer patients who received Cmab containing therapy. Main eligibility criteria were >=3 Cmab administrations, no prior EGFR-directed therapy, and no prophylactic Mg supplementation. RESULTS: Median baseline serum Mg level and number of Cmab administrations were 2.2 mg/dl and 8, respectively. Overall incidence of hypomagnesemia was 50.4% (grade 1, 46.6%; grade 2, 3.1%; grade 3, 0%; and grade 4, 0.8%) and differed between patients treated with palliative chemotherapy and bioradiation (Cmab and radiation) (63 versus 24%; P < 0.01). Independent risk factors were low baseline serum Mg [odds ratio (OR) 161.988, 95% confidence interval (CI) 9.436-2780.895], >=7 Cmab administrations (OR 3.56, 95% CI 1.16-13.98), and concurrent administration of platinum (cisplatin; OR 23.695, 95% CI 5.219-107.574, carboplatin; OR 5.487, 95% CI 1.831-16.439). Respective incidence of hypomagnesemia in patients in high- (concurrent platinum and >=7 Cmab administrations) and low-risk (no concurrent platinum and <7 Cmab administrations) groups was 66.0 and 6.6% (P < 0.001, OR 28.0). CONCLUSION: Cmab is associated with a significant risk of hypomagnesemia in patients with head and neck cancer with longer term administration and concurrent platinum therapy. High risk patients should be treated with particular care. PMID- 27683628 TI - BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection. AB - Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research. PMID- 27683642 TI - Dry needling in patients with chronic heel pain due to plantar fasciitis: A single-blinded randomized clinical trial. AB - BACKGROUND: This study examined the effects of dry needling on chronic heel pain due to plantar fasciitis. METHODS: During this single-blinded clinical trial, 20 eligible patients were randomized into two groups: A case group treated with dry needling and a control group. Patients' plantar pain severity, (using modified visual analog scale [VAS] scoring system), range of motion of ankle joint in dorsiflexion [ROMDF] and plantar extension[ROMPE] and foot function index (using standard questionnaires of SEM5 and MDC7) were assessed at baseline, four weeks after intervention and four weeks after withdrawing treatment. Independent sample t-test, Mann-Whitney U test, paired t-test, Wilcoxon signed rank tests, and chi square test were used for data analysis. RESULTS: The mean VAS scores in the case group was significantly lower than the control group after four weeks of intervention (p<0.001). Comparison of the ROMDF and ROMPE did not reveal any significant changes after four weeks of intervention in the case and control groups (p=0.7 and p=0.65, respectively). The mean of MDC7 and SEM5 scores in the case group were significantly lower than the control group following four weeks of intervention (p<0.001). CONCLUSION: Despite the insignificant effect on ROMDF and ROMPE, trigger point dry needling, by improving the severity of heel pain, can be used as a good alternative option before proceeding to more invasive therapies of plantar fasciitis. PMID- 27683643 TI - Concise, intensive or longitudinal medical education courses, which is more effective in perceived self-efficacy and development of faculty members? AB - BACKGROUND: Teachers' self-efficacy and development may be conceptualized as their beliefs in their own ability to plan, organize and carry out activities that are required to attain educational goals. In this study, we examined the effect of different medical education training courses (six-day, one- month short term and sixmonth long- term courses) on perceived self-efficacy and development. METHODS: This before-after quasi-experimental study was performed on 39 faculty members of Tehran University of Medical Sciences who participated in faculty development courses in 2013. We used valid and reliable scales to measure their perceived self-efficacy and empowerment. RESULTS: The results revealed a significant increase in faculty members' perceived self-efficacy in pre and posttests in one-month and six-month courses, but no significant difference was found in the six-day course (p=0.004, p<0.001 and p=0.235, respectively). These results were the same for perceived empowerment (p<0.001, p<0.001 and p=0.716 for one-month, six-month and six-day courses, respectively). A significant difference was detected in perceived self-efficacy and participant empowerment components based on the training course (p=0.005; Wilk's Lambda=0.345, Partial eta2=0.413). CONCLUSION: This study revealed that long- term courses were more effective than the short- term ones. Thus, longitudinal courses are recommended for more effectiveness. PMID- 27683641 TI - Chicken gga-miR-19a Targets ZMYND11 and Plays an Important Role in Host Defense against Mycoplasma gallisepticum (HS Strain) Infection. AB - Mycoplasma gallisepticum (MG), one of the most pathogenic Mycoplasmas, can cause chronic respiratory disease (CRD) in chickens. It has been suggested that micro ribonucleic acids (miRNAs) are involved in microbial pathogenesis. However, little is known about the roles of miRNAs in MG infection. Previously, we found by deep sequencing that gga-miR-19a was significantly up-regulated in the lungs of MG-infected chicken embryos. In this work, we confirmed that gga-miR-19a was up-regulated in both MG-infected chicken embryonic lungs and MG-infected DF-1 (chicken embryo fibroblast) cells. At 72 h post-transfection, we found that the over-expression of gga-miR-19a significantly enhanced the proliferation of MG infected DF-1 cells by promoting the transition from the G1 phase to the S and G2 phases, while a gga-miR-19a inhibitor repressed the proliferation of MG-infected DF-1 cells by arresting the cell cycle in the G1 phase. Moreover, we found that gga-miR-19a regulated the expression of the host zinc-finger protein, MYND-type containing 11 (ZMYND11), through binding to its 3' untranslated region (3'-UTR). DAVID analysis revealed that ZMYND11 could negatively regulate the NF-kappaB (NF kappaB) signaling pathway in chickens (Gallus gallus). Upon MG infection, gga-miR 19a, NF-kappaB, MyD88, and TNF-alpha were all up-regulated, whereas ZMYND11 was down-regulated. The over-expression of gga-miR-19a in the DF-1 cells did not affect the above gene expression patterns, and gga-miR-19a inhibitor repressed the expression of NF-kappaB, MyD88, and TNF-alpha, but enhanced the expression of ZMYND11. In conclusion, gga-miR-19a might suppress the expression of ZMYND11 in MG-infected chicken embryonic lungs and DF-1 cells, activate the NF-kappaB signaling pathway, and promote pro-inflammatory cytokines expression, the cell cycle progression and cell proliferation to defend against MG infection. PMID- 27683644 TI - Contextualization and validation of the interprofessional collaborator assessment rubric (ICAR) through simulation: Pilot investigation. AB - BACKGROUND: Simulation can be used for educating, evaluating and assessing psychometric properties of an instrument. The aim of this study was to contextualize and assess the validity and reliability of the Interprofessional Collaborative Assessment tool (ICAR) in an Iranian context using simulation. METHODS: In this descriptive study, contextualization of the ICAR was assessed through several steps. Firstly, validity assessment was approved through expert panels and Delphi rounds. Secondly, reliability assessment was done by arranging a simulation video and assessing reproducibility, test-retest (ICC), internal consistency (Cronbach's Alpha) and inter-rater reliability (Kappa).The participants included 26 experts, 27 students and 6 staff of the Standardized Simulation Office of Teheran University of Medical Sciences. RESULTS: Contextualization and validity of the ICAR were approved in an Iranian context. The reliability of the tool was computed to be 0.71 according to Cronbach's Alpha. The test-retest was calculated to be 0.76. CONCLUSION: The Iranian ICAR can be a useful tool for evaluating interprofessional collaborative competencies. The development of the instrument through a simulation scenario has been a positive prospect for researchers. PMID- 27683645 TI - Does outsourcing paramedical departments of teaching hospitals affect educational status of the students? AB - BACKGROUND: There is an increasing trend of outsourcing public departments. Teaching hospitals also outsourced some of their departments to private sectors. The aim of this study was to investigate and compare the educational status of students in public and outsourced departments of teaching hospitals affiliated to Iran University of Medical Sciences. METHODS: This study was conducted in six teaching hospitals of Iran University of Medical Sciences, which had public and outsourced teaching departments in 2015. One hundred fifty students from the departments of radiology, physiotherapy and laboratory participated in this study and their perceptions about their educational status were assessed. A valid and reliable questionnaire was used; participation in the study was voluntary. Descriptive statistics such as mean (SD), t-test and Kolmogorov-Smirnov were used. RESULTS: No difference was detected between the educational status of students in public and outsourced departments of radiology, physiotherapy and laboratory (p>0.05). CONCLUSION: Based on the students' perception, the private sectors could maintain the educational level of the teaching departments similar to the public departments. It is recommended to involve all the stakeholders such as hospital administrators, academic staff and students in the decision- making process when changes in teaching environments are being considered. PMID- 27683646 TI - Sensitivity to nitazoxanide among metronidazole resistant Helicobacter pylori strains in patients with gastritis. AB - BACKGROUND: In this study, the efficacy of nitazoxanide in the treatment of Helicobacter pylori isolates, which were resistant to metronidazole, was examined. METHODS: One hundred twenty two patients who underwent endoscopy examinations at Kasra and Laleh hospitals in Tehran from November 2014 to July 2015 were enrolled. Helicobacter pylori strains were isolated from the patients' endoscopy biopsies by bacteriological culture. Those bacterial isolates resistant to metronidazole were examined for susceptibility to nitazoxanide. Serial agar dilution method was utilized to determine the minimum inhibitory concentrations for the antibiotics. RESULTS: From 122 gastric biopsy specimens, 55 H. pylori isolates were recovered (45%); of which, 40 (72.7%) were resistant to metronidazole. Comparing the MIC values of nitazoxanide with metronidazole revealed significant differences (p<0.05). The MIC50 and MIC90 values for nitazoxanide and metronidazole were 8 and >=8MUg/ml, and 32 and 64MUg/ml, respectively. CONCLUSION: The high levels of metronidazole resistance suggest that this medication may not be beneficial for first-line therapy in Iran. However, considering the relative effectiveness of nitazoxanide, it may be considered a suitable alternative for patients in Iran. PMID- 27683647 TI - The effect of educational programs based on the theory of planned behavior on parental supervision in students' television watching. AB - BACKGROUND: Excessive and uncontrolled television watching by children predisposes them to some risks such as developmental, social and psychological disorders. Parents play an important role in nurturing their children and controlling the factors affecting their health. The aim of this study was to determine the impact of health education programs on parents' supervision skills to control their children's television watching habits based on the theory of planned behavior. METHODS: One hundred twenty parents of the students at the first and fifth grades of primary school were randomly divided into an intervention and a control group. Data were collected by a self-report questionnaire at the beginning of and one month after intervention. An educational intervention was implemented for the case group parents, who were divided into four 15-member groups, in the form of three 45-60 minute sessions with focus group discussions. Moreover, the parents were provided with children and television booklet. Data were entered into SPSS-16 and were analyzed using Chi-square, paired t test, Mann-Whitney and Wilcoxon tests. RESULTS: After the intervention, significant changes were detected in the intervention group with respect to the mean hours of watching television (from 6.74+/-2.02 to 4.28+/ 2.40; p= 0.039), knowledge scores (from 5.8+/-2.1 to 7.7+/-1.9; p= 0.001), attitude towards less television watching (from 35.5+/-11.5 to 48.4+/-8.9; p=0.003), subjective norms (from 11.8+/-8.1 to 24.5+/-8.6; p>0.001) and behavioral intention (from 18.6+/-7.4 to 31.8+/-5.1; p=0.001). CONCLUSION: The results revealed that educational interventions based on the theory of planned behavior are capable of changing knowledge, attitude, subjective norm and intention of parents towards controlling and monitoring their children's television watching and can improve the performance of parental control and reduce the hours of TV watching by children. Therefore, this pattern is suggested for reforming the nurturing skills of parents about other behavioral problems of their children. PMID- 27683648 TI - Designing a national plan for improving sexual health in Iran: An experience of an Islamic country. AB - BACKGROUND: Prevalence of sexual dysfunction varies from 20% to 40% in men and women in different studies in Iran. Despite its high prevalence, it seems that this issue has been neglected, particularly in Islamic countries. The aim of this study was to assess sexual health in Iran. This was a mixed method study. METHODS: Data were collected through evaluating country's sexual health programs and literature review. Sexual health status was drafted and formed following a sound analysis by stakeholders. After conducting interviews and focus group discussions, the main points of the meetings, influencing factors of the present status and oncoming strategies were obtained upon experts' opinions. RESULTS: Review of general policies and the literature showed that although there is adequate support for improving sexual health status in the country, sexual health status has been decreased in the last decade. Based on Iranian sexual health indicators and experts' opinions, the focus points could be divided into the following groups: Structural and functional -political, legal-behavior, and cultural. CONCLUSION: Breaking the taboo of sexual health issues would require attention from the policy makers especially in Islamic nations to facilitate the steps on the road to sexual health. In this regard, clarified vision, strategic goals and interventional policies are proposed. An inter-sectional cooperation is needed to implement interventions to promote sexual health status. PMID- 27683649 TI - How to integrate social care services into primary health care? An experience from Iran. AB - BACKGROUND: Social issues have prominent effects on the peoples' physical and mental health and on the health risk factors. In Iran, many organizations provide social care services to their target population. This study aimed to explore the roles and functions of Primary Health Care (PHC) system in providing social care services in Iran. METHODS: This was a qualitative study, for which data were collected via three sources: A review of the literature, in-depth interviews and focus group discussions with experts and stakeholders. The main objective was to find a way to integrate social care into the Iranian PHC system. A conventional content analysis was performed to explore the data. RESULTS: Overall, 20 experts were interviewed and the acquired data were classified into four major categories including priorities, implementation, requirements and stewardship. The main challenges were the existing controversies in the definition of social care, social service unit disintegration, multiple stewards for social care services, weaknesses of rules and regulations and low financing of the public budget. Social care services can be divided into two categories: Basic and advanced. Urban and rural health centers, as the first level of PHC, could potentially provide basic social care services for their defined population and catchment areas such as detecting social harms in high risk individuals and families and providing counseling for people in need. They can also refer the individuals to receive advanced services. CONCLUSION: Iran has a successful history of establishing the PHC System especially in rural areas. This network has an invaluable capacity to provide social health services. Establishing these services needs some prerequisites such as a reform PHC structure, macro support and technical intersectoral collaboration. They should also be piloted and evaluated before they could be implemented in the whole country. PMID- 27683650 TI - Effective factors in expansion of medical tourism in Iran. AB - BACKGROUND: Medical tourism (MT) refers to circumstances in which people travel for medical treatments. The present study focuses on determining factors affecting MT in Iran. METHODS: The study uses a mixed method approach. Initially, through a qualitative study, 12 experts were interviewed deeply; then, 22 participants in three equal focus groups expressed their ideas about growth and development of MT in Iran. Based on the expressed ideas, 120 factors were identified and accordingly a structured questionnaire was developed. Some members from the focus groups confirmed the questionnaire's face and content validity. The reliability of pertinent items was confirmed using Cronbach's alpha=0.8. Afterwards, 61 eligible subjects filled out this questionnaire. RESULTS: The findings showed that "healthcare quality" and "high level of expertise" are two most attractive factors in MT. However, other factors such as "healthcare costs", and "visa facilities" are among key factors as well. Also, the role of "the healthcare providers" was found to be more prominent than the roles of "the government" and "the general tourist services". CONCLUSION: Although some attractive MT factors are present currently, MT expansion to a desirable level in Iran requires a comprehensive plan of which its factors were discussed in this paper. PMID- 27683651 TI - Manipulation of IL-10 gene expression by Toxoplasma gondii and its products. AB - BACKGROUND: This study was designed to evaluate whether or not T. gondii and its derivatives can change the gene expression level of IL-10 in murine leukocytes in vivo. METHODS: Fifty BALB/c mice were divided into 5 groups, four of which received the excretory/secretory product (ESP) from cell culture medium, the ESP from cell free medium, the Toxoplasma lysate product (TLP) and the active tachyzoites, respectively. The fifth group was considered as control and received PBS. The peritoneal leukocytes from the mice were collected. Their total RNA were extracted and converted to cDNA and the gene expression levels of IL-10 in the samples were evaluated by quantitative real time-PCR using the REST-2009 software. RESULTS: The findings showed a decrease in the expression level of IL 10 in the TLP group (p=0.004). Moreover, the IL-10 gene expression level was upregulated in the group of the ESP from cell culture medium (p=0.04) and the active tachyzoite group (p=0.04). The expression of IL-10 gene in the group of ESP from cell-free medium was not significant compared to the control one (p=0.45). CONCLUSION: T. gondii and its derivatives are able to increase (the active T. gondii tachyzoite and the ESP from cell culture medium) and decrease (the TLP) the gene expression level of IL-10 in a murine model. The question remains to be examined in further study about which molecules are involved in this process. PMID- 27683652 TI - Atypical Manifestation of LPS-Responsive Beige-Like Anchor Deficiency Syndrome as an Autoimmune Endocrine Disorder without Enteropathy and Immunodeficiency. AB - Monogenic primary immunodeficiency syndromes can affect one or more endocrine organs by autoimmunity during childhood. Clinical manifestations include type 1 diabetes mellitus, hypothyroidism, adrenal insufficiency, and vitiligo. Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency was described in 2012 as a novel primary immunodeficiency, predominantly causing immune dysregulation and early onset enteropathy. We describe the heterogeneous clinical course of LRBA deficiency in two siblings, mimicking an autoimmune polyendocrine disorder in one of them in presence of the same underlying genetic mutation. The third child of consanguineous Egyptian parents (Patient 1) presented at 6 months of age with intractable enteropathy and failure to thrive. Later on, he developed symptoms of adrenal insufficiency, autoimmune hemolytic anemia, thrombocytopenia, and infectious complications due to immunosuppressive treatment. The severe enteropathy was non-responsive to the standard treatment and led to death at the age of 22 years. His younger sister (Patient 2) presented at the age of 12 to the endocrinology department with decompensated hypothyroidism, perioral vitiligo, delayed pubertal development, and growth failure without enteropathy and immunodeficiency. Using whole exome sequencing, we identified a homozygous frameshift mutation (c.6862delT, p.Y2288MfsX29) in the LRBA gene in both siblings. To our knowledge, our patient (Patient 2) is the first case of LRBA deficiency described with predominant endocrine phenotype without immunodeficiency and enteropathy. LRBA deficiency should be considered as underlying disease in pediatric patients presenting with autoimmune endocrine symptoms. The same genetic mutation can manifest with a broad phenotypic spectrum without genotype-phenotype correlation. The awareness for disease symptoms among non-immunologists might be a key to early diagnosis. Further functional studies in LRBA deficiency are necessary to provide detailed information on the origin of autoimmunity in order to develop reliable predictive biomarkers for affected patients. PMID- 27683653 TI - Antibody Drug Conjugates Differentiate Uptake and DNA Alkylation of Pyrrolobenzodiazepines in Tumors from Organs of Xenograft Mice. AB - Pyrrolobenzodiazepine (PBD)-dimer is a DNA minor groove alkylator, and its CD22 THIOMAB antibody drug conjugate (ADC) demonstrated, through a disulfide linker, an efficacy in tumor reduction for more than 7 weeks with minimal body weight loss in xenograft mice after a single 0.5-1 mg/kg i.v. dose. The DNA alkylation was investigated here in tumors and healthy organs of mice to understand the sustained efficacy and tolerability. The experimental procedures included the collection of tumors and organ tissues of xenograft mice treated with the ADC followed by DNA isolation/hydrolysis/quantitation and payload recovery from reversible DNA alkylation. PBD-dimer formed a considerable amount of adducts with tissue DNA, representing approximately 98% (at 24 hours), and 99% (at 96 hours) of the total PBD-dimer in tumors, and 78-89% in liver and lung tissues, suggesting highly efficient covalent binding of the released PBD-dimer to tissue DNA. The amount of PBD-DNA adducts in tumor tissues was approximately 24-fold (at 24 hours) and 70-fold (at 96 hours) greater than the corresponding amount of adducts in liver and lung tissues. In addition, the DNA alkylation levels increased 3-fold to 4-fold from 24 to 96 hours in tumors [41/106 base pairs (bp) at 96 hours] but remained at the same level (1/106 bp) in livers and lungs. These results support the typical target-mediated cumulative uptake of ADC into tumors and payload release that offers an explanation for its sustained antitumor efficacy. In addition, the low level of DNA alkylation in normal tissues is consistent with the tolerability observed in mice. PMID- 27683654 TI - Things I wish I'd known: desiderata for early career psychiatrists. AB - OBJECTIVE: The objective of this study was to disseminate advice imparted to early career psychiatrists by a panel of senior colleagues at a Royal Australian and New Zealand College of Psychiatrists symposium, reflecting on things they wished they had known at the earlier stage in their careers. METHODS: Key themes were extracted from notes taken at the symposium, where opinions were expressed by three senior psychiatrists. RESULTS: There are components in building a sustainable career as a psychiatrist, which include considering one's work environment and relationships with colleagues; self-care, mentorship and reflective practice; and seeking opportunities to teach and research for career progression. CONCLUSIONS: The mentorship and advice from senior colleagues can be highly influential. In order to sustain a career that has reward, meaning and longevity, psychiatrists would do well to pay attention to aspects of self-care, stay connected to their loved ones, seek an optimal work-life balance and take an interest in their long term career plans. PMID- 27683655 TI - Mental health services planning for G20 summit in Brisbane and assessment of impact. AB - OBJECTIVE: The objective of this study was to inform planning for similar events, our aim was to describe planning undertaken by Brisbane Mental Health Services for the 2014 G20 Summit and the impact of the Summit on service use. METHODS: We analysed routinely collected service data comparing presentations and discharges for the same time period in two consecutive years. RESULTS: While presentations to mental health services increased from the previous year across a five-month period (including the month of G20), the week of the G20 Summit showed little change. CONCLUSIONS: Our findings will be useful to other services that prepare for major events, such as G20. Our experience shows that, with detailed planning and extra resources, the G20 Summit passed without any major mental health incidents or major increase for mental health presentations. PMID- 27683657 TI - Methylphenidate in the treatment of an adolescent female with obsessive compulsive disorder and attention deficit hyperactivity disorder: a case report. AB - OBJECTIVES: We describe a case whereby a 15-year-old female with treatment resistant obsessive-compulsive disorder (OCD) was treated with methylphenidate for co-morbid attention deficit hyperactivity disorder (ADHD). The ADHD-OCD co morbidity has often been overlooked clinically due to conflicting opinions about their underlying neurobiology and treatment options. CONCLUSIONS: In this adolescent with co-morbid ADHD and OCD, we observed that the adjunctive use of methylphenidate resulted in enhanced treatment response to both psychological and pharmacological interventions for OCD. This case highlights the need to identify and treat co-morbid ADHD in OCD cases where progress has stalled. PMID- 27683656 TI - Effectiveness of a single day induction programme in changing medical students' attitudes towards the speciality of forensic psychiatry. AB - OBJECTIVES: We aimed to investigate the effectiveness of a day visit in changing attitudes towards a high-security forensic psychiatric hospital, with regard to the current recruitment difficulties in psychiatry. METHODS: Broadmoor Hospital, a UK high-security psychiatric hospital, runs day visits for medical students, led by doctors. At the beginning and the end of the day students wrote their responses to the question, 'What do you think of Broadmoor?' Attitudes and themes were identified, and their prevalence was analysed. RESULTS: The responses of 296 students were initially analysed; however, 19 responses had to be excluded because they were illegible or incomplete. Before the visit, 15 responses were rated as positive, 169 neutral and 93 negative. After the visit, 205 responses were positive, 69 neutral and three negative. The themes that changed markedly following the visit were those indicating a change to favourable attitude. CONCLUSIONS: A single day visit was shown to be effective in altering the attitudes of medical students towards forensic psychiatry within a high-security psychiatric hospital. PMID- 27683658 TI - Value Chains of Public and Private Health-care Services in a Small EU Island State: A SWOT Analysis. AB - The global financial and macroeconomic crisis of 2008/2009 and the ensuing recessions obliged policy makers to maximize use of resources and cut down on waste. Specifically, in health care, governments started to explore ways of establishing collaborations between the public and private health-care sectors. This is essential so as to ensure the best use of available resources, while securing quality of delivery of care as well as health systems sustainability and resilience. This qualitative study explores complementary and mutual attributes in the value creation process to patients by the public and private health-care systems in Malta, a small European Union island state. A workshop was conducted with 28 professionals from both sectors to generate two separate value chains, and this was followed by an analysis of strengths, weaknesses, opportunities, and threats (SWOT). The latter revealed several strengths and opportunities, which can better equip health-policy makers in the quest to maximize provision of health-care services. Moreover, the analysis also highlighted areas of weaknesses in both sectors as well as current threats of the external environment that, unless addressed, may threaten the state's health-care system sustainability and resilience to macroeconomic shocks. The study goes on to provide feasible recommendations aimed at maximizing provision of health-care services in Malta. PMID- 27683659 TI - DGK-theta: Structure, Enzymology, and Physiological Roles. AB - Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Merida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al., 2011; Tu-Sekine et al., 2013) among others]. We now know there are ten mammalian DGKs that are organized into five classes. DGK-theta is the lone member of the Type V class of DGKs and remains as one of the least studied. This review focuses on our current understanding of the structure, enzymology, regulation, and physiological roles of this DGK and suggests some future areas of research to understand this DGK isoform. PMID- 27683660 TI - Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1. AB - The budding yeast Candida albicans is one of the most significant fungal pathogens worldwide. It proliferates in two distinct cell types: blastopores and filaments. Only cells that are able to transform from one cell type into the other are virulent in mouse disease models. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We now provide evidence that suggests that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Finally, our genetic data suggests that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1. PMID- 27683661 TI - "Don't Believe Your Eyes" Ipratropium Induced Mydriasis: A Case Report and Review of the Literature. AB - Unilateral fixed mydriasis can be an ominous sign; however in many cases, it is benign and represents pharmacologic mediated action on the iris dilator or sphincter. Differentiation between pharmacologic mediated anisocoria and physiologic anisocoria can be challenging but may save on costly imaging. An 83 year-old woman was admitted with critical limb ischemia and subsequently developed respiratory failure treated with positive pressure ventilation and ipratropium nebulizers. She was noted to have left unilateral mydriasis without other neurologic deficits. Brain magnetic resonance imaging with MR angiography showed no evidence for a mass lesion or posterior communicating artery aneurysm. Her anisocoria self-resolved within 36 hours after nebulizer treatments were stopped. Ipratropium bromide is one of the most common medications used in the hospital setting and should be consider as a possible etiology when examining patients with unilateral mydriasis in the absence of other neurologic findings. PMID- 27683662 TI - Does community-based suicide prevention decrease suicide attempts? Strategies for reaching zero suicide. PMID- 27683663 TI - Using Electronic Health Record Data to Identify Prostate Cancer Patients That May Qualify for Active Surveillance. AB - INTRODUCTION: The introduction of the protein-specific antigen (PSA) test in care means that prostate cancer (PCa) is being detected earlier and more frequently. The result of increased screening using PSA, digital rectal examination and awareness of prostate was an increase in the number of men with low risk cancers. Active surveillance has become a viable alternative to immediate treatment with surgery, radiation and other forms of localized treatment. Evidence suggests that there is no significant difference in mortality rates between AS and surgery. In addition, patients may potentially delay other complications associated with surgery, radiation or deprivation therapy. METHODS: This quality improvement study using a delivery system science framework describes the electronic identification of AS candidates given an evidence-based identification criteria based upon national guidelines and clinical judgement. The study population (n=649) was drawn from health records of all patients who received a prostate biopsy (n=1731) at Intermountain Healthcare from 1/1/2013 to 12/31/2014. Automated and manual abstraction was performed. Receiver operating characteristic (ROC) analysis was used to compare AS-eligible patients to the actual treatment received to identify potential care improvement opportunities. Among those with complete data, 24.7% of this population (n=160) met "AS-eligible" criteria. 39.1% of the population had not received surgery, radiation or androgen deprivation therapy and were considered as being treated using an AS approach. 9% of AS eligible patients did not receive AS; 27% of patients who did not meet AS eligible criteria received AS. Estimated guideline adherence measured using area under the curve was 0.70 (95% CI: 0.66-0.73). Modest variation in criteria parameters for identifying AS-eligible patients did not significantly change estimated adherence levels. CONCLUSION: Implementation of evidence-based criteria for detection of AS candidates is feasible using electronic health record data and provides a reasonable basis for delivery system evaluation of practice patterns and for quality improvement. PMID- 27683664 TI - Using Machine Learning and Natural Language Processing Algorithms to Automate the Evaluation of Clinical Decision Support in Electronic Medical Record Systems. AB - INTRODUCTION: As the number of clinical decision support systems (CDSSs) incorporated into electronic medical records (EMRs) increases, so does the need to evaluate their effectiveness. The use of medical record review and similar manual methods for evaluating decision rules is laborious and inefficient. The authors use machine learning and Natural Language Processing (NLP) algorithms to accurately evaluate a clinical decision support rule through an EMR system, and they compare it against manual evaluation. METHODS: Modeled after the EMR system EPIC at Maine Medical Center, we developed a dummy data set containing physician notes in free text for 3,621 artificial patients records undergoing a head computed tomography (CT) scan for mild traumatic brain injury after the incorporation of an electronic best practice approach. We validated the accuracy of the Best Practice Advisories (BPA) using three machine learning algorithms-C Support Vector Classification (SVC), Decision Tree Classifier (DecisionTreeClassifier), k-nearest neighbors classifier (KNeighborsClassifier) by comparing their accuracy for adjudicating the occurrence of a mild traumatic brain injury against manual review. We then used the best of the three algorithms to evaluate the effectiveness of the BPA, and we compared the algorithm's evaluation of the BPA to that of manual review. RESULTS: The electronic best practice approach was found to have a sensitivity of 98.8 percent (96.83-100.0), specificity of 10.3 percent, PPV = 7.3 percent, and NPV = 99.2 percent when reviewed manually by abstractors. Though all the machine learning algorithms were observed to have a high level of prediction, the SVC displayed the highest with a sensitivity 93.33 percent (92.49-98.84), specificity of 97.62 percent (96.53 98.38), PPV = 50.00, NPV = 99.83. The SVC algorithm was observed to have a sensitivity of 97.9 percent (94.7-99.86), specificity 10.30 percent, PPV 7.25 percent, and NPV 99.2 percent for evaluating the best practice approach, after accounting for 17 cases (0.66 percent) where the patient records had to be reviewed manually due to the NPL systems inability to capture the proper diagnosis. DISCUSSION: CDSSs incorporated into EMRs can be evaluated in an automatic fashion by using NLP and machine learning techniques. PMID- 27683665 TI - Framework for Deploying a Virtualized Computing Environment for Collaborative and Secure Data Analytics. AB - INTRODUCTION: Large amounts of health data generated by a wide range of health care applications across a variety of systems have the potential to offer valuable insight into populations and health care systems, but robust and secure computing and analytic systems are required to leverage this information. FRAMEWORK: We discuss our experiences deploying a Secure Data Analysis Platform (SeDAP), and provide a framework to plan, build and deploy a virtual desktop infrastructure (VDI) to enable innovation, collaboration and operate within academic funding structures. It outlines 6 core components: Security, Ease of Access, Performance, Cost, Tools, and Training. CONCLUSION: A platform like SeDAP is not simply successful through technical excellence and performance. It's adoption is dependent on a collaborative environment where researchers and users plan and evaluate the requirements of all aspects. PMID- 27683666 TI - A Focus Group Exploration of Automated Case-Finders to Identify High-Risk Heart Failure Patients Within an Urban Safety Net Hospital. AB - BACKGROUND: Leveraging "big data" as a means of informing cost-effective care holds potential in triaging high-risk heart failure (HF) patients for interventions within hospitals seeking to reduce 30-day readmissions. OBJECTIVE: Explore provider's beliefs and perceptions about using an electronic health record (EHR)-based tool that uses unstructured clinical notes to risk-stratify high-risk heart failure patients. METHODS: Six providers from an inpatient HF clinic within an urban safety net hospital were recruited to participate in a semistructured focus group. A facilitator led a discussion on the feasibility and value of using an EHR tool driven by unstructured clinical notes to help identify high-risk patients. Data collected from transcripts were analyzed using a thematic analysis that facilitated drawing conclusions clustered around categories and themes. RESULTS: From six categories emerged two themes: (1) challenges of finding valid and accurate results, and (2) strategies used to overcome these challenges. Although employing a tool that uses electronic medical record (EMR) unstructured text as the benchmark by which to identify high-risk patients is efficient, choosing appropriate benchmark groups could be challenging given the multiple causes of readmission. Strategies to mitigate these challenges include establishing clear selection criteria to guide benchmark group composition, and quality outcome goals for the hospital. CONCLUSION: Prior to implementing into practice an innovative EMR-based case-finder driven by unstructured clinical notes, providers are advised to do the following: (1) define patient quality outcome goals, (2) establish criteria by which to guide benchmark selection, and (3) verify the tool's validity and reliability. Achieving consensus on these issues would be necessary for this innovative EHR based tool to effectively improve clinical decision-making and in turn, decrease readmissions for high-risk patients. PMID- 27683667 TI - v3NLP Framework: Tools to Build Applications for Extracting Concepts from Clinical Text. AB - INTRODUCTION: Substantial amounts of clinically significant information are contained only within the narrative of the clinical notes in electronic medical records. The v3NLP Framework is a set of "best-of-breed" functionalities developed to transform this information into structured data for use in quality improvement, research, population health surveillance, and decision support. BACKGROUND: MetaMap, cTAKES and similar well-known natural language processing (NLP) tools do not have sufficient scalability out of the box. The v3NLP Framework evolved out of the necessity to scale-up these tools up and provide a framework to customize and tune techniques that fit a variety of tasks, including document classification, tuned concept extraction for specific conditions, patient classification, and information retrieval. INNOVATION: Beyond scalability, several v3NLP Framework-developed projects have been efficacy tested and benchmarked. While v3NLP Framework includes annotators, pipelines and applications, its functionalities enable developers to create novel annotators and to place annotators into pipelines and scaled applications. DISCUSSION: The v3NLP Framework has been successfully utilized in many projects including general concept extraction, risk factors for homelessness among veterans, and identification of mentions of the presence of an indwelling urinary catheter. Projects as diverse as predicting colonization with methicillin-resistant Staphylococcus aureus and extracting references to military sexual trauma are being built using v3NLP Framework components. CONCLUSION: The v3NLP Framework is a set of functionalities and components that provide Java developers with the ability to create novel annotators and to place those annotators into pipelines and applications to extract concepts from clinical text. There are scale-up and scale-out functionalities to process large numbers of records. PMID- 27683668 TI - Leadership Perspectives on Operationalizing the Learning Health Care System in an Integrated Delivery System. AB - INTRODUCTION: Healthcare leaders need operational strategies that support organizational learning for continued improvement and value generation. The learning health system (LHS) model may provide leaders with such strategies; however, little is known about leaders' perspectives on the value and application of system-wide operationalization of the LHS model. The objective of this project was to solicit and analyze senior health system leaders' perspectives on the LHS and learning activities in an integrated delivery system. METHODS: A series of interviews were conducted with 41 system leaders from a broad range of clinical and administrative areas across an integrated delivery system. Leaders' responses were categorized into themes. FINDINGS: Ten major themes emerged from our conversations with leaders. While leaders generally expressed support for the concept of the LHS and enhanced system-wide learning, their concerns and suggestions for operationalization where strongly aligned with their functional area and strategic goals. DISCUSSION: Our findings suggests that leaders tend to adopt a very pragmatic approach to learning. Leaders expressed a dichotomy between the operational imperative to execute operational objectives efficiently and the need for rigorous evaluation. Alignment of learning activities with system-wide strategic and operational priorities is important to gain leadership support and resources. Practical approaches to addressing opportunities and challenges identified in the themes are discussed. CONCLUSION: Continuous learning is an ongoing, multi-disciplinary function of a health care delivery system. Findings from this and other research may be used to inform and prioritize system-wide learning objectives and strategies which support reliable, high value care delivery. PMID- 27683669 TI - Using a Patient Portal to Transmit Patient Reported Health Information into the Electronic Record: Workflow Implications and User Experience. AB - INTRODUCTION: This project implemented an integrated patient self-reported screening tool in a patient portal and assessed clinical workflow and user experience in primary care practices. METHODS: An electronic health risk assessment based on the CMS Annual Wellness Visit (AWV) was developed to integrate self-reported health information into the patient's electronic health record (EHR). Patients enrolled in care coordination tested the implementation. The evaluation plan included quantitative and qualitative measures of patient adoption, provider adoption, workflow impact, financial impact, and technology impact. FINDINGS: Seventy-two patients completed the sample AWV, and 80% of the questionnaires had clinical findings that required provider follow-up. Patients expressed satisfaction with the portal, as it enabled them to view their health record and enter information. Implementation did not reduce office staff time. Providers and office staff agreed that an electronic system for adding information to their record would increase patient satisfaction, but they expressed concern with the need to promptly review the information and the time involved to accomplish this prior to an office visit. DISCUSSION: Despite satisfaction among patients, portal adoption is still low, due to technological limitations and to the lack of adaptability to primary care practice workflow. Notwithstanding those barriers, the use of the portal for completion of repetitive tasks, such as screening tools, should be encouraged. CONCLUSIONS: Patients can effectively use portals to complete the patient reported section of the CMS AWV. However, if the information is not completed during the same day of the office visit, the time required to address health findings outside of a regular office visit is uncompensated, and diminished the enthusiasm for this process among primary care practice staff. PMID- 27683670 TI - Introduction of an Area Deprivation Index Measuring Patient Socioeconomic Status in an Integrated Health System: Implications for Population Health. AB - INTRODUCTION: Intermountain Healthcare is a fully integrated delivery system based in Salt Lake City, Utah. As a learning healthcare system with a mission of performance excellence, it became apparent that population health management and our efforts to move towards shared accountability would require additional patient-centric metrics in order to provide the right care to the right patients at the right time. Several European countries have adopted social deprivation indices in measuring the impact that social determinants can have on health. Such indices provide a geographic, area-based measure of how socioeconomically deprived residents of that area are on average. Intermountain's approach was to identify a proxy measure that did not require front-line data collection and could be standardized for our patient population, leading us to the area deprivation index or ADI. This paper describes the specifications and calculation of an ADI for the state of Utah. Results are presented along with introduction of three use cases demonstrating the potential for application of an ADI in quality improvement in a learning healthcare system. CASE DESCRIPTION: The Utah ADI shows promise in providing a proxy for patient-reported measures reflecting key socio economic indicators useful for tailoring patient interventions to improve health care delivery and patient outcomes. Strengths of this approach include a consistent standardized measurement of social determinants, use of more granular block group level measures and a limited data capture burden for front-line teams. While the methodology is generalizable to other communities, results of this index are limited to block groups within the state of Utah and will differ from national calculations or calculations for other states. The use of composite measures to evaluate individual characteristics must also be approached with care. Other limitations with the use of U.S. Census data include use of estimates and missing data. CONCLUSION: Initial applications in three meaningfully different areas of an integrated health system provide initial evidence of its broad applicability in addressing the impact of social determinants on health. The variation in socio-economic status by quintile also has potential for clinical significance, though more research is needed to link variation in ADI with variation in health outcomes overall and by disease type. PMID- 27683671 TI - Concordium 2015: Strategic Uses of Evidence to Transform Delivery Systems. AB - In September 2015 the EDM Forum hosted AcademyHealth's newest national conference, Concordium. The 11 papers featured in the eGEMs "Concordium 2015" special issue successfully reflect the major themes and issues discussed at the meeting. Many of the papers address informatics or methodological approaches to natural language processing (NLP) or text analysis, which is indicative of the importance of analyzing text data to gain insights into care coordination and patient-centered outcomes. Perspectives on the tools and infrastructure requirements that are needed to build learning health systems were also recurrent themes. PMID- 27683673 TI - Parent & Child Perceptions of Child Health after Sibling Death. AB - BACKGROUND: Understanding children's health after a sibling's death and what factors may affect it is important for treatment and clinical care. This study compared children's and their parents' perceptions of children's health and identified relationships of children's age, gender, race/ethnicity, anxiety, and depression and sibling's cause of death to these perceptions at 2 and 4 months after sibling death. METHODS: 64 children and 48 parents rated the child's health "now" and "now vs before" the sibling's death in an ICU or ER or at home shortly after withdrawal of life-prolonging technology. Children completed the Child Depression Inventory and Spence Children's Anxiety Scale. Sibling cause of death was collected from hospital records. RESULTS: At 2 and 4 months, 45% to 54% of mothers' and 53% to 84% of fathers' ratings of their child's health "now" were higher than their children's ratings. Child health ratings were lower for: children with greater depression; fathers whose children reported greater anxiety; mothers whose child died of a chronic condition. Children's ratings of their health "now vs before" their sibling's death did not differ significantly from mothers' or fathers' ratings at 2 or 4 months. Black fathers were more likely to rate the child's health better "now vs before" the death; there were no significant differences by child gender and cause of death in child's health "now vs before" the death. CONCLUSIONS: Children's responses to a sibling's death may not be visually apparent or become known by asking parents. Parents often perceive their children as healthier than children perceive themselves at 2 and 4 months after sibling death, so talking with children separately is important. Children's perceptions of their health may be influenced by depression, fathers' perceptions by children's anxiety, and mother's perceptions by the cause of sibling death. PMID- 27683672 TI - Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging. AB - Hypertension is nearly universal yet poorly controlled in the elderly despite proven benefits of intensive treatment. Mice lacking mineralocorticoid receptors in smooth muscle cells (SMC-MR-KO) are protected from rising blood pressure (BP) with aging, despite normal renal function. Vasoconstriction is attenuated in aged SMC-MR-KO mice, thus they were used to explore vascular mechanisms that may contribute to hypertension with aging. MicroRNA (miR) profiling identified miR 155 as the most down-regulated miR with vascular aging in MR-intact but not SMC MR-KO mice. The aging-associated decrease in miR-155 in mesenteric resistance vessels was associated with increased mRNA abundance of MR and of predicted miR 155 targets Cav1.2 (L-type calcium channel (LTCC) subunit) and angiotensin type-1 receptor (AgtR1). SMC-MR-KO mice lacked these aging-associated vascular gene expression changes. In HEK293 cells, MR repressed miR-155 promoter activity. In cultured SMCs, miR-155 decreased Cav1.2 and AgtR1 mRNA. Compared to MR-intact littermates, aged SMC-MR-KO mice had decreased systolic BP, myogenic tone, SMC LTCC current, mesenteric vessel calcium influx, LTCC-induced vasoconstriction and angiotensin II-induced vasoconstriction and oxidative stress. Restoration of miR 155 specifically in SMCs of aged MR-intact mice decreased Cav1.2 and AgtR1 mRNA and attenuated LTCC-mediated and angiotensin II-induced vasoconstriction and oxidative stress. Finally, in a trial of MR blockade in elderly humans, changes in serum miR-155 predicted the BP treatment response. Thus, SMC-MR regulation of miR-155, Cav1.2 and AgtR1 impacts vasoconstriction with aging. This novel mechanism identifies potential new treatment strategies and biomarkers to improve and individualize antihypertensive therapy in the elderly. PMID- 27683676 TI - Spine surgery in Nepal: the 2015 earthquake. AB - At noon on Saturday, 25 April 2015, a 7.8 magnitude earthquake struck Nepal. It was centered in the Himalaya northwest of Kathmandu, the capital of over 1 million people. The violent tremors were felt as far away as New Delhi, India 1,000 km from the epicenter, but the worst of its destructive force was experienced in the heavily populated Kathmandu valley and in the remote mountainous villages of the Himalaya. Ancient temples crumbled; poorly constructed buildings collapsed; men, women, and children were trapped and injured, sometimes fatally. Avalanches killed mountain climbers, Sherpa guides, and porters at Everest base camp (EBC). The death toll to date exceeds 8,600 with as many as 20,000 injured. Spinal Health International (SHI), a nonprofit volunteer organization, has been active in Nepal in past years and responded to requests by Nepali spine surgeons for assistance with traumatic spine injury victims following the earthquake. SHI volunteers were present during the 2(nd) major earthquake of magnitude 7.3 on 12 May 2015. Past and current experiences in Nepal will be presented. PMID- 27683675 TI - Systematic reviews and meta-analyses in spine surgery, neurosurgery and orthopedics: guidelines for the surgeon scientist. AB - The research evidence in the realm of surgery is expanding at a rapid pace, and thus corresponds with an increasing need to critically appraise and synthesize the available literature. Particularly in fields such as spine surgery, neurosurgery and orthopedics which traditionally have little Class I randomized clinical data, reviews are important to pool the available evidence on clinical questions which are otherwise difficult to answer. Whilst systematic reviews and meta-analyses have the potential to provide critical and updated surgical evidence to guide clinical decisions, poorly performed analyses and misinterpretation of such reviews may have a detrimental effect on patient care and outcomes. We present a summary of the critical steps in performing a systematic review and meta-analysis, allowing the surgeon scientist to better interpret and perform their own systematic reviews and meta-analyses. PMID- 27683674 TI - Lumbar interbody fusion: techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF/ATP, LLIF and ALIF. AB - Degenerative disc and facet joint disease of the lumbar spine is common in the ageing population, and is one of the most frequent causes of disability. Lumbar spondylosis may result in mechanical back pain, radicular and claudicant symptoms, reduced mobility and poor quality of life. Surgical interbody fusion of degenerative levels is an effective treatment option to stabilize the painful motion segment, and may provide indirect decompression of the neural elements, restore lordosis and correct deformity. The surgical options for interbody fusion of the lumbar spine include: posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), minimally invasive transforaminal lumbar interbody fusion (MI-TLIF), oblique lumbar interbody fusion/anterior to psoas (OLIF/ATP), lateral lumbar interbody fusion (LLIF) and anterior lumbar interbody fusion (ALIF). The indications may include: discogenic/facetogenic low back pain, neurogenic claudication, radiculopathy due to foraminal stenosis, lumbar degenerative spinal deformity including symptomatic spondylolisthesis and degenerative scoliosis. In general, traditional posterior approaches are frequently used with acceptable fusion rates and low complication rates, however they are limited by thecal sac and nerve root retraction, along with iatrogenic injury to the paraspinal musculature and disruption of the posterior tension band. Minimally invasive (MIS) posterior approaches have evolved in an attempt to reduce approach related complications. Anterior approaches avoid the spinal canal, cauda equina and nerve roots, however have issues with approach related abdominal and vascular complications. In addition, lateral and OLIF techniques have potential risks to the lumbar plexus and psoas muscle. The present study aims firstly to comprehensively review the available literature and evidence for different lumbar interbody fusion (LIF) techniques. Secondly, we propose a set of recommendations and guidelines for the indications for interbody fusion options. Thirdly, this article provides a description of each approach, and illustrates the potential benefits and disadvantages of each technique with reference to indication and spine level performed. PMID- 27683677 TI - Foraminal height measurement techniques. AB - BACKGROUND: One of the proposed advantages of anterior lumbar interbody fusion (ALIF) is restoration of disc height and hence an indirect foraminal height restoration. While this proposed advantage is often quoted in the literature, there are few robust studies demonstrating restoration of foraminal volume. Thus, this study aimed to review the literature and discuss the progression and development of foramen measurement techniques. METHODS: A review of the literature was performed to identify studies which reported foraminal height and dimensions following fusion surgery in cadaveric models or patients. RESULTS: Techniques in prior studies used to quantify foraminal dimensions before and after fusion operations include analysis from plain radiographs, computed tomography (CT) scans and magnetic resonance imaging (MRI) scans. Recent studies have attempted to standardize foraminal dimension measurements with the use of orthogonal software, accelerator-based measurements and the use of multiple images for three-dimensional reconstruction of the foramen volume. CONCLUSIONS: Consistent results have demonstrated significant increases in foraminal area and height following anterior lumbar interbody distraction, providing evidence that ALIF can indirectly increase foraminal height. Future studies should use standardized measurement approaches such as the Pedicle-to-Pedicle technique with CT or MRI images to determine changes in foraminal dimensions. PMID- 27683678 TI - Technical note: microdiscectomy and translaminar approach. AB - Lumbar disk herniation (LDH) is a degenerative pathology. Although LDH generally occurs without migration of the fragment to the levels above or below, in 10% of the cases, this circumstance might happen. In these cases, the standard interlaminar approach, described by Caspar cannot be performed without laminotomies, interlaminectomies, or partial or total facetectomies. The translaminar approach is the only "tissue-sparing" technique viable in cases of cranially migrated LDH encroaching on the exiting nerve root in the preforaminal zones, for the levels above L2-L3, and in the preforaminal and foraminal zones, for the levels below L3-L4 (L5-S1 included, if a total microdiscectomy is unnecessary). This approach is more effective than the standard one, because it resolves the symptoms; it is associated with less postoperative pain and faster recovery times without the risk of iatrogenic instability, and it can also be used in cases with previous signs of radiographic instability. The possibility to spare the flavum ligament is one of the main advantages of this technique. For these reasons, the translaminar approach is a valid technique in terms of safety and efficacy. In this article the surgical technique will be extensively analyzed and the tips and tricks will be highlighted. PMID- 27683680 TI - Rural neurosurgical and spinal laboratory setup. AB - BACKGROUND: Increasing focus has been placed on the use of simulation in neurosurgical and spinal surgical training worldwide, with the establishment of many surgical laboratories dedicated to such purpose. So far, the opportunities for hands-on cadaveric training in the areas of neurosurgery and spine surgery remain limited in Australia, owing to various factors, including the abolition of dissection in many medical schools, high maintenance requirements and widespread geographical distribution of surgical trainees. METHODS: We established a cadaver based neurosurgical laboratory based at the medical school of the University of New England in Armidale, Australia, which is used by the surgical dissection course for junior surgical trainees offered by the university. We reported our experiences in setting up a neurosurgical research laboratory, and explored the feasibility of establishing a cost-effective anatomical research facility in a rural setting in Australia. RESULTS: We found that Genelyn(TM)-fixed cadavers had limited movements of the head as required for adequate surgical positioning and exposure. Furthermore, we discovered that bodies embalmed via the femoral vein had poorly perfused heads after surgical exposure, and thus decapitation had to be performed unfortunately for our purpose. Cadaver samples and surgical equipment were sourced from various veterinary practices and commercial companies. Using human and animal cadavers, this laboratory provided trainees with hands-on opportunities to improve their surgical skills and neuroanatomical knowledge, as well as develop familiarity with highly specialized surgical equipment. CONCLUSIONS: We demonstrated the feasibility of establishing a cost effective neurosurgical research laboratory in Australia and discussed various aspects of its maintenance. PMID- 27683681 TI - Surgery for spinal tuberculosis: a multi-center experience of 582 cases. AB - BACKGROUND: Tuberculosis (TB) of the spine is a common site of osseous TB, accounting for 50%-60% of cases. Spinal TB still occurs in both developed and developing countries. The diagnosis of spinal TB is difficult and it commonly presents at an advanced stage. Delays in establishing diagnosis and management result in complications such as spinal cord compression and spinal deformity. METHODS: A total of 582 patients with TB of the cervical, thoracic and lumbar spine with moderate to severe cord compression were studied. Variable degrees of neurological deficit with deformity were treated from January, 2003 to July, 2014. Thoracotomy along with anterolateral decompression and autogenous strut bone grafting with simultaneous fixation by screws and rods were performed in 113 cases. Posterior decompression, posterior interbody and posterolateral fusion by bone graft with stabilization by transpedicular screws and rods were done in the remaining 469 cases. Appropriate anti-TB drugs were given to all patients for 18 24 months. The follow-up period was 3 months to 10 years. RESULTS: The average age was 32.5 years. All patients survived surgery. There were 7 cases of superficial infections (1.2%) whilst there were 4 cases (0.7%) of deep infections. Revision surgery was performed in 6 patients (1.0%). Implant failure occurred in 4 cases (0.7%) whilst malposition of screws occurred in 12 cases (2.1%). Perioperative bleeding complications were reported for 4 patients (0.7%). Neurological improvement occurred in all patients except for 2 cases (0.3%). Preoperatively, the majority of patients (n=221, 38%) were classified with Class A on the American Spinal Injury Association (ASIS) neurological impairment scale. This was significantly reduced postoperatively to 0.4%. CONCLUSIONS: For patients with spinal TB anterior debridement, auto graft bone fusion, anterior or posterior fixation appears to be effective in arresting disease, correcting kyphotic deformity and maintaining correction until solid spinal fusion. PMID- 27683679 TI - The outcome of pedicle screw instrumentation removal for ongoing low back pain following posterolateral lumbar fusion. AB - BACKGROUND: Our aim was to determine whether patients derived benefit from removal of pedicle screw instrumentation for axial pain without other cause using our surgical technique and patient selection. A secondary aim was to investigate factors that were associated with poorer outcomes for this procedure as well as complication rate in this cohort. METHODS: Theater records from a single spinal surgeon's practice were reviewed to identify patients that had undergone lumbar fusion for discogenic back pain with subsequent pedicle screw instrumentation removal (Expedium, DePuy Synthes) in the preceding 3 years with a minimum of 18 months follow-up. Inclusion criteria were persisting midline axial back pain with computed tomography (CT)-confirmed solid fusion with non-radicular symptoms and nil other potential causes found, e.g., infection. Case note review along with pre- and post-operative Oswestry disability index (ODI) questionnaires and visual analog scores (VAS) were assessed for all patients. Surgical technique included re-use of previous midline posterior incision and the Wiltse approach with removal of implants, confirmation of a solid fusion mass, washout and bone grafting of removal sites. RESULTS: From 50 consecutive patients who underwent removal of posterolateral instrumentation for an index elective lumbar fusion for discogenic back pain, 34 patients were identified that met the criteria with a mean follow-up of 25 months (range, 18-36 months). The VAS and ODI improved in 22/34 (65%) of participants. The mean cohort VAS score was 6.6 pre-surgery and 4.3 post-surgery (P=0.04). Preoperative and postoperative mean Oswestry disability scores were 64 and 41, respectively (P=0.05). There was a statistically significant difference in the proportion of patients with poorer compared to satisfactory outcomes with regards to compensable status, preoperative grade II opioid use and shorter time between fusion and removal procedure. Complications were one postoperative hematoma and one superficial wound infection, both of which settled without re-operation. CONCLUSIONS: Approximately two thirds of patients were satisfied with removal of instrumentation for treatment of residual low back pain (LBP) following elective lumbar fusion and recorded reduced VAS and grade II opioid use. A subset of patients remained that did not derive benefit and were associated with compensable status, preoperative grade II opioid use and a shorter time between fusion and removal procedure. A prospective cohort study with preoperative diagnostic injections and standardized imaging and microscopic techniques would strengthen future studies. However, this study suggests that removal of instrumentation is safe and provides modest benefit as a palliative procedure for a subset of patients with significant disability from chronic LBP without an underlying cause following lumbar fusion. PMID- 27683683 TI - Treatment of symptomatic thoracic disc herniations with lateral interbody fusion. AB - BACKGROUND: Symptomatic thoracic herniated discs have historically been treated using open exposures (i.e., thoracotomy), posing a clinical challenge given the approach related morbidity. Lateral interbody fusion (LIF) is one modern minimally disruptive alternative to thoracotomy. The direct lateral technique for lumbar pathologies has seen a sharp increase in procedural numbers; however application of this technique in thoracic pathologies has not been widely reported. METHODS: This study presents the results of three cases where LIF was used to treat symptomatic thoracic disc herniations. Indications for surgery included thoracic myelopathy, radiculopathy and discogenic pain. Patients were treated with LIF, without supplemental internal fixation, and followed for 24 months postoperatively. RESULTS: Average length of hospital stay was 5 days. One patient experienced mild persistent neuropathic thoracic pain, which was managed medically. At 3 months postoperative all patients had returned to work and by 12 months all patients were fused. From preoperative to 24-month follow-up there were mean improvements of 83.3% in visual analogue scale (VAS), 75.3% in Oswestry Disability Index (ODI), and 79.2% and 17.4% in SF-36 physical (PCS) and mental component scores (MCS), respectively. CONCLUSIONS: LIF is a viable minimally invasive alternative to conventional approaches in treating symptomatic thoracic pathology without an access surgeon, rib resection, or lung deflation. PMID- 27683682 TI - Anterior cervical disc arthroplasty (ACDA) versus anterior cervical discectomy and fusion (ACDF): a systematic review and meta-analysis. AB - BACKGROUND: Surgical approaches are usually required in cases of severe cervical disc disease. The traditional method of anterior cervical disc fusion (ACDF) has been associated with reduced local mobility and increased occurrence of adjacent segment disease. The newer method of anterior cervical disc arthroplasty (ACDA) relies upon artificial discs of various products. Current literature is inconsistent in the comparative performance of these methods with regards to clinical, radiological and patient outcomes. METHODS: Electronic databases, including OVID Medline, PubMed, Scopus, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, were comprehensively searched to retrieve studies comparing the treatment outcomes of ACDF and ACDA. Baseline characteristics and outcome data were extracted from eligible articles. RESULTS: Two hundred and fifty five articles were identified through the database searches, and after screening 28 studies were included in the systematic review and meta-analysis. A total of 4,070 patients were included (2156 ACDA, 1914 ACDF). There was no significant difference between the two groups in operation time, blood loss during operation, long-term all-complication rate and reoperation rate at the level of injury. The ACDA group had significantly better neurological outcomes, as well as a significantly lower rate of adjacent segment diseases. CONCLUSIONS: Compared with ACDF, the ACDA procedure is associated with improved reoperation rate and reduction in neurological deficits amongst previously demonstrated benefits. There is heterogeneity in ACDA devices; future studies are required to investigate the impact of this technique on treatment outcomes. PMID- 27683685 TI - Malignant paraganglioma, a rare presentation with foot drop: a case report. AB - Paragangliomas (or extra-adrenal paragangliomas) are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. This is in contrast to pheochromocytomas, where tumors occur in the adrenal gland. Malignant paraganglioma is a very rare presentation. We present a case report of a 56-year old woman with acute foot drop with no previous significant background history. To the best of our knowledge, the current case represents the first case of malignant paraganglioma with acute foot drop presentation. PMID- 27683684 TI - Granular cell tumors of the spinal canal: intramedullary case report and a review of the literature. PMID- 27683687 TI - From small seeds grow big trees. PMID- 27683686 TI - Axial interbody arthrodesis of the L5-S1 segment: a systematic review of the literature. PMID- 27683688 TI - Comparison of ALIF vs. XLIF for L4/5 interbody fusion: pros, cons, and literature review. AB - The incidence of lumbar fusion for the treatment of various degenerative lumbar spine diseases has increased dramatically over the last twenty years. Many lumbar fusion techniques have been developed and popularized, each with its own advantages and disadvantages. Anterior lumbar interbody fusion (ALIF) initially introduced in the 1930's, has become a common and widely accepted technique for lumbar fusions over the last decade offering several advantages over standard posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (TLIF). More recently, the lateral trans-psoas approach termed extreme, direct or lateral lumbar interbody fusion (XLIF, DLIF, LLIF) is gaining widespread popularity. The aim of this paper is to compare the approaches, advantages and disadvantages of ALIF and XLIF for L4/5 interbody fusion based on relevant literature. PMID- 27683689 TI - Bone morphogenetic protein in pediatric spine fusion surgery. AB - BACKGROUND: There is a paucity of literature describing the use of bone graft substitutes to achieve fusion in the pediatric spine. Outcomes and complications involving the off-label use of bone morphogenetic protein 2 (BMP-2) in the pediatric spine are not clearly defined. The purpose of this study is to review the existing literature with respect to reported outcomes and complications involving the use of low-dose BMP-2 in pediatric patients. METHODS: A Medline and PubMed literature search was conducted using the words bone morphogenetic protein, BMP, rh-BMP-2, bone graft substitutes, and pediatric spine. RESULTS: To date, there are few published reports on this topic. Complications and appropriate BMP-2 dosage application in the pediatric spine remain unknown. CONCLUSIONS: This report describes the potential for BMP-2 to achieve successful arthrodesis of the spine in pediatric patients. Usage should be judicious as complications and long-term outcomes of pediatric BMP-2 usage remain undefined in the existing literature. PMID- 27683690 TI - Third-generation percutaneous vertebral augmentation systems. AB - Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting((r)) (VBS), OsseoFix((r)) and Spine Jack((r)). VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix((r)) and Spine Jack((r)) are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix((r)) has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting((r)) and Spine Jack((r)), the OsseoFix((r)) has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack((r)) is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors. PMID- 27683691 TI - Surgical treatment of far lateral lumbar disc herniation: a safe and simple approach. AB - Lumbar discectomy is one of the most commonly performed neurosurgical procedure. Far lateral disc herniations (FLDH) make up a minor portion of the total discectomy workload for spine surgeons. Due to their lower incidence, as well as their different anatomical positioning compared to the more common para-median disc herniation, the surgical procedures involved in releasing the neural compression caused by FLDHs are often challenging and at times frustrating to most spine surgeons, resulting in suboptimal outcomes for the patient related to the higher risk of spinal instability from facet joint disruption and may even be associated with nerve root injury. We discuss here a safe and simple approach to tackle FLDH. PMID- 27683692 TI - Comparison of surgical outcomes after anterior cervical discectomy and fusion: does the intra-operative use of a microscope improve surgical outcomes. AB - BACKGROUND: The primary aim of this study was to assess and compare the complications profile as well as long-term clinical outcomes between patients undergoing an Anterior Cervical Discectomy and Fusion (ACDF) procedure with and without the use of an intra-operative microscope. METHODS: One hundred and forty adult patients (non-microscope cohort: 81; microscope cohort: 59) undergoing ACDF at a major academic medical center were included in this study. Enrollment criteria included available demographic, surgical and clinical outcome data. All patients had prospectively collected patient-reported outcomes measures and a minimum 2-year follow-up. Patients completed the neck disability index (NDI), short-form 12 (SF-12) and visual analog pain scale (VAS) before surgery, then at 3, 6, 12, and 24 months after surgery. Clinical outcomes and complication rates were compared between both patient cohorts. RESULTS: Baseline characteristics were similar between both cohorts. The mean +/- standard deviation duration of surgery was longer in the microscope cohort (microscope: 169+/-34 minutes vs. non microscope: 98+/-42 minutes, P<0.001). There was no significant difference between cohorts in the incidence of nerve root injury (P=0.99) or incidental durotomy (P=0.32). At 3 months post-operatively, both cohorts demonstrated similar improvement in VAS-neck pain (P=0.69), NDI (P=0.86), SF-12 PCS (P=0.84) and SF-12 MCS (P=0.75). At 2-year post-operatively, both the microscope and non microscope cohorts demonstrated similar improvement from base line in NDI (microscope: 13.52+/-25.77 vs. non-microscope: 19.51+/-27.47, P<0.18), SF-12 PCS (microscope: 4.15+/-26.39 vs. non-microscope: 11.98+/-22.96, P<0.07), SF-12 MCS (microscope: 9.47+/-32.38 vs. non-microscope: 16.19+/-30.44, P<0.21). Interestingly at 2 years, the change in VAS neck pain score was significantly different between cohorts (microscope: 2.22+/-4.00 vs. non-microscope: 3.69+/ 3.61, P<0.02). CONCLUSIONS: Our study demonstrates that the intra-operative use of a microscope does not improve overall surgery-related outcomes, nor does it lead to superior long-term outcomes in pain and functional disability, 2 years after index surgery. PMID- 27683693 TI - Interspinous process spacers versus traditional decompression for lumbar spinal stenosis: systematic review and meta-analysis. AB - BACKGROUND: Interspinous spacers are used in selected patients for the treatment of lumbar spinal stenosis. The uses of interspinous devices are still debated, with reports of significantly higher reoperation rates and unfavourable cost effectiveness compared to traditional decompression techniques. METHODS: Six electronic databases were searched from their date of inception to December 2015. Relevant studies were identified using specific eligibility criteria and data was extracted and analyzed based on predefined primary and secondary endpoints. RESULTS: Eleven comparative studies were obtained for qualitative and quantitative assessment, data extraction and analysis. There was no significant difference in VAS back pain, leg pain or ODI scores for standalone interspinous process device (IPD) vs. bony decompression. However, standalone IPD was associated with lower surgical complications (4% vs. 8.7%, P=0.03) but higher long-term reoperation rates (23.7% vs. 8.5%, P<0.00001). IPD as an adjunct to decompression had comparable patient-reported scores, complications and reoperation rates to decompression alone. CONCLUSIONS: Current evidence indicates no superiority for mid- to long-term patient-reported outcomes for IPD compared with traditional bony decompression, with lesser surgical complications but at the risk of significantly higher reoperation rates and costs. PMID- 27683694 TI - Cervical spine immobilization in the elderly population. AB - BACKGROUND: Immobilization of the cervical spine is a cornerstone of spinal injury management. In the context of suspected cervical spine injury, patients are immobilized in a 'neutral position' based on the head and trunk resting on a flat surface. It is hypothesized that the increased thoracic kyphosis and loss of cervical lordosis seen in elderly patients may require alternative cervical immobilization, compared with the 'neutral position'. METHODS: To investigate this, an audit of pan-scan CT performed on consecutive major trauma patients aged over 65 years was carried out over a 6-month period. Utilizing the pan-CT's localizing scout film, a novel measurement, the 'chin-brow horizontal' angle was independently measured by a senior spine surgeon (RJM) and a neurosurgeon (PJR) with the gantry used as a horizontal zero- degree reference. The benefit of the 'chin-brow horizontal' angle in the trauma setting is it can be assessed from the bedside whilst the patient is immobilized against a flat surface. RESULTS: During the 6-month study period, 58 patients were identified (30 male, 28 female), with an average age of 77.6 years (minimum 65, maximum 97). Results showed that 'chin brow horizontal' angles varied widely, between +15.8 degrees in flexion to -30.5 degrees in extension (mean -12.4 degrees in extension, standard deviation 9.31 degrees. The interobserver correlation was 0.997 (95% CI: 0.995-0.998). CONCLUSIONS: These findings suggest that, due to degenerative changes commonly seen in elderly patients, the routine use of the 'neutral position' adopted for cervical spine immobilization may not be appropriate in this population. We suggest that consideration be taken in cervical spine immobilization, with patients assessed on an individual basis including the fracture morphology, to minimize the risk of fracture displacement and worsened neurological deficit. PMID- 27683695 TI - Independent predictors of reliability between full time employee-dependent acquisition of functional outcomes compared to non-full time employee-dependent methodologies: a prospective single institutional study. AB - BACKGROUND: The prospective acquisition of reliable patient-reported outcomes (PROs) measures demonstrating the effectiveness of spine surgery, or lack thereof, remains a challenge. The aims of this study are to compare the reliability of functional outcomes metrics obtained using full time employee (FTE) vs. non-FTE-dependent methodologies and to determine the independent predictors of response reliability using non FTE-dependent methodologies. METHODS: One hundred and nineteen adult patients (male: 65, female: 54) undergoing one- and two-level lumbar fusions at Duke University Medical Center were enrolled in this prospective study. Enrollment criteria included available demographic, clinical and baseline functional outcomes data. All patients were administered two similar sets of baseline questionnaires-(I) phone interviews (FTE-dependent) and (II) hardcopy in clinic (patient self-survey, non-FTE dependent). All patients had at least a two-week washout period between phone interviews and in-clinic self-surveys to minimize effect of recall. Questionnaires included Oswestry disability index (ODI) and Visual Analog Back and Leg Pain Scale (VAS-BP/LP). Reliability was assessed by the degree to which patient responses to baseline questionnaires differed between both time points. RESULTS: About 26.89% had a history an anxiety disorder and 28.57% reported a history of depression. At least 97.47% of patients had a High School Diploma or GED, with 49.57% attaining a 4-year college degree or post-graduate degree. 29.94% reported full-time employment and 14.28% were on disability. There was a very high correlation between baseline PRO's data captured between FTE-dependent compared to non-FTE-dependent methodologies (r=0.89). In a multivariate logistic regression model, the absence of anxiety and depression, higher levels of education (college or greater) and full-time employment, were independently associated with high response reliability using non-FTE-dependent methodologies. CONCLUSIONS: Our study suggests that capturing health-related quality of life data using non-FTE-dependent methodologies is highly reliable and maybe a more cost-effective alternative. Well-educated patients who are employed full-time appear to be the most reliable. PMID- 27683696 TI - Decompression versus decompression and fusion for degenerative lumbar stenosis: analysis of the factors influencing the outcome of back pain and disability. AB - BACKGROUND: The objective of this study is to evaluate the factors influencing the outcome of back pain and disability in patients operated for lumbar stenosis without instability and deformity using two classical surgical techniques: decompression alone and decompression plus fusion. METHODS: This is a retrospective cohort study of patients who underwent lumbar surgery with standard posterior decompression or standard posterior decompression plus pedicle screw fixation for degenerative lumbar stenosis without deformity, spondylolisthesis or instability at our department from June 2010 to January 2014. They were divided into two groups: decompression group (D) and decompression-fusion group (F). We analyzed the following factors: age, gender, levels of stenosis, pre-surgical "micro-instability", and post-surgical "micro-instability". RESULTS: A total of 174 patients were enrolled in the study. Both Graphic Rating Scale (GRS) and Oswestry Disability Index (ODI) scores were significantly decreased after surgery (P<0.001). Female patients appeared to have lesser improvements from surgery, for both D and F groups. An analysis of variance using the decrease of pain (GRS pre post) as dependent variable and type of surgery, age, gender and their interaction as factors showed that the main effects of type of surgery and gender were significant. The analysis of variance for the decrease of pain (GRS) and disability (ODI) according to the levels of stenosis showed a significant interaction for GRS scores. Female patients that underwent fixation surgery reported the least improvement in disability. A significant interaction was found on the one-way analysis of variance for the D group without pre-surgical micro instability using post-surgical micro-instability as factor. CONCLUSIONS: Our study supports posterior decompression alone as the gold standard option as treatment for lumbar stenosis without instability and deformity. Additional fusion should be considered only to prevent post-surgical instability. The "micro instability" is a radiological finding that has its clinical surrogate but is not able to guide the choice of the type of surgery. Moreover the significance of "micro-instability" is still unclear. We suggest a prospective study following patients with asymptomatic micro-instability to definitively understand the clinical history. PMID- 27683698 TI - Kyphotic deformity after laminectomy surgery for a gunshot wound to the spine: a case report. AB - Spinal kyphotic deformity after spinal laminectomy or laminoplasty is more common in pediatric patients than adults. Laminectomy can lead to decreased cartilage growth, anterior wedging and posterior spinal muscle insufficiency which can result in kyphotic deformity. Herein we outline a case report of a child presenting with kyphotic deformity after receiving a spinal laminectomy to treat a penetrating spinal trauma. The 8-year-old male presented with penetrating spinal trauma following a gunshot wound and subsequently underwent L1 laminectomy and thecal sac decompression to remove the foreign body. In a follow-up examination approximately one month after surgery, imaging revealed kyphotic deformity and the patient was referred to the Rasoul-e-Akram Hospital. The patient then underwent surgical reconstruction. The postoperative computed tomography (CT) scan showed appropriate repair of sagittal balance and the patient's symptoms gradually improved. Post-laminectomy kyphosis is a notable concern and complication in the pediatric population and can occur shortly after surgery. The following interventions can decrease the likelihood of post laminectomy kyphosis: minimal muscle dissection and bone removal during laminectomy, avoidance of facet disruption, use of laminoplasty rather than laminectomy, postoperative immobilization/bracing and regular follow-up for early detection and treatment of any deformity. PMID- 27683697 TI - Far lateral microdiscectomy: a minimally-invasive surgical technique for the treatment of far lateral lumbar disc herniation. AB - Lumbar disc herniation arises when the annulus fibrosus of the vertebral disc fails, thus allowing displacement of the nucleus pulposus and other tissue. The term far lateral is used variably in the literature and usually refers to an extraforaminal displacement in the peridiscal zone peripheral to the sagittal plane of the most lateral part of the pedicle at the same level. Non-surgical treatments of far lateral disc herniation include physical therapy, anti inflammatory medication, and corticosteroid injections. Where these conservative measures fail, surgical intervention may be required. Several surgical techniques for the treatment of far lateral herniations have been investigated, including total or medial facetectomy, laminectomy, hemilaminectomy, approaches through the pars interarticularis, and lateral approaches between the transverse processes via the intertransverse muscle and ligament. We present our far lateral microdiscectomy technique which involves accessing the nerve root lateral to the foramen through a small paramedian incision and use of an operating microscope. Far lateral microdiscectomy offers the prospect of better long-term results than other surgical techniques because of less extensive muscle dissection and preservation of the integrity of the facet joint. PMID- 27683699 TI - Acute hemorrhagic paraplegia in a thoracic spinal hemangioblastoma after free diving. PMID- 27683700 TI - Scoliosis associated with idiopathic lumbosacral epidural lipomatosis. AB - There are very few reports of spinal epidural lipomatosis (SEL) in association with scoliosis. A 49-year-old man presented with persistent back pain and right hip lump. The lumbar spine X-rays showed scoliosis (Lenke classification 5BN). Lumbar MRI demonstrated circumferential epidural fat deposit from L1 to lower S2 level. There was no obvious etiology of SEL except mild increased body mass index (BMI). The patient was managed with conservative treatment. After 6 months medication (limaprost and ginkgo), his symptoms were relieved. PMID- 27683701 TI - Neurotropic cutaneous malignant melanoma with contiguous spread to spinal cord, an extremely rare presentation. AB - Neurotropic melanoma (NM) is a rare variant of cutaneous melanomas. Compared with conventional melanoma, NM is more locally aggressive with an increased tendency for local recurrence but less likely for nodal or distant metastases. The often amelanotic, benign appearance may lead to treatment issues such as late presentation, diagnostic delay, misdiagnosis, insufficient surgical margins, and recurrence with resulting poor outcome. To our knowledge, this is the first case report of NM with contiguous spread to the spinal cord. We present a case report of a 73-year-old male with gradual decline in mobility over the period of few months. He deteriorated very rapidly whilst inpatient with progressive myelopathy, loss of sphincter function and dysphonia with dysphagia due to involvement of lower cranial nerves. The neurotropic nature of the disease and prevalence in the head and neck region results in perineural and neural invasion with resulting neuropathies. Patient underwent posterior cervical decompression and resection of the higher cervical intramedullary spinal cord NM lesion. He recovered well with improvement of his limb weakness as well as bulbar function. Wide local excision (WLE) with adjuvant radiotherapy where indicated remains the current practice for treatment, with chemotherapy predominately being reserved as a salvage treatment for patients with disseminated disease. PMID- 27683702 TI - Adjacent segment degeneration and disease following cervical arthroplasty: a systematic review and meta-analysis. PMID- 27683703 TI - Percutaneous resolution of lumbar facet joint cysts as an alternative treatment to surgery: a meta-analysis. PMID- 27683704 TI - Surgery for spinal stenosis: more thought, less metal? PMID- 27683706 TI - Anterior cervical discectomy and fusion (ACDF) autograft versus graft substitutes: what do patients prefer?-A clinical study. AB - BACKGROUND: Patient dissatisfaction with donor site morbidity has led to the search for alternative grafting options and techniques. This report compares patient satisfaction rates between autograft and graft substitutes for anterior cervical discectomy and fusion (ACDF). METHODS: This study was performed with the approval of the local area health network ethics committee. Over a 9-year period, the author performed 574 ACDF procedures (697 levels). Of these, 22 patients had previous surgery with autograft, with a subsequent ACDF procedure performed using a graft substitute. Patients rated their satisfaction with pain, recovery, and preference of autograft versus a bone graft substitute. Graft substitutes used include: tricalcium phosphate/hydroxyapatite (TCP/HA) composite and iFactor placed within a polyetheretherketone (PEEK) cage. RESULTS: Results demonstrated that 21/22 patients achieved a solid fusion with the graft substitute. A total of 20/22 patients rated the autograft incision more painful than the anterior cervical incision, and 21/22 preferred the graft substitute. Three patients had adjacent segment disc replacement performed after autograft/ACDF. All patients reported preference for the total disc replacement (TDR) procedure in terms of recovery and postoperative pain. CONCLUSIONS: Patient satisfaction with bone graft substitutes is very high compared with autograft with all but one (21/22) preferring the graft substitute option. The author questions the traditional recommendation that autograft is the "gold standard" for ACDF. In modern age of graft substitutes, autograft should not be considered the gold standard, but an index option between other options for comparison. PMID- 27683705 TI - Minimally invasive surgery in adult degenerative scoliosis: a systematic review and meta-analysis of decompression, anterior/lateral and posterior lumbar approaches. AB - BACKGROUND: Minimally invasive approaches for the treatment of adult degenerative scoliosis have been increasingly implemented. However, little data exists regarding the safety and complication profiles of minimally invasive lumbar interbody fusion (LIF) for adult degenerative scoliosis. This study aimed to greater understand different minimally invasive surgical approaches for adult degenerative scoliosis with respect to clinical outcomes, changes in radiographic measurements, and complication profiles via meta-analytical techniques. METHODS: A systematic search of six databases from inception to September 2015 was performed by two independent reviewers. Relevant studies were those that described the safety and/or effectiveness of minimally invasive anterior or lateral LIF (LLIF), transforaminal LIF (TLIF), and decompression only. Meta analytical techniques and meta-regression were used to pool overall rates, and compare the different techniques. There was no financial funding or conflict of interest. RESULTS: A total of 29 studies (1,228 patients) were included in this meta-analysis. Total pooled fusion rate was 95.9% (95% CI: 92.7-98.2%) for the anterior/lateral approach. The pooled construct or hardware-related complications was 4.3%, and was similar among anterior/lateral (4.4%) and posterior (5.2%) techniques. The total pooled pseudoarthrosis rate was 4.3% for the lateral approach. The overall pooled rate of motor deficit was 2.7% (95% CI: 1.7-4.0%). Subgroup meta-regression demonstrated that the anterior/lateral approach had the highest rate of motor deficits (3.6% LLIF vs. 0.7% TLIF vs. 0.5% decompression, P=0.004). The overall pooled rate of sensory deficit was 2.4%, highest for the anterior/lateral technique (3.3%) compared to TLIF (0.7%) and decompression (0.5%). The infection rate, dural tears/CSF leak, cardiac and pulmonary events were similar among the techniques, with a pooled value of 2.6%, 3.9%, 1.7%, and 1.4%, respectively. Similarly satisfactory radiological outcomes were obtained amongst the different approaches. CONCLUSIONS: Minimally invasive spine technologies may be used for the surgical treatment of lumbar degenerative scoliosis with acceptable complication rates, functional and radiological outcome. Future studies, specifically multi-centered longitudinal, examining the adequacy of minimally invasive spine surgery is warranted to compare long-term outcomes with the traditional procedure. PMID- 27683708 TI - Percutaneous thoracolumbar decompression combined with percutaneous pedicle screw fixation and fusion: a method for treating spinal degenerative pain in a biplane angiography suite with the avoidance of general anesthesia. AB - BACKGROUND: Spondylytic degeneration of the axial lumbar spine is a major cause of pain and disability. Recent advances in spinal surgical instrumentation, including percutaneous access and fusion techniques, have made possible the performance of instrumented fusion through small incisions. By blending strategies of interventional pain management, neuroradiology, and conventional spine surgery, it is now feasible to treat spinal axial pain using permanent fixation techniques and local anesthesia in the setting of a fluoroscopy suite using mild sedation and local anesthesia. METHODS: The author presents a series of percutaneous thoracolumbar fusion procedures performed in a biplane neuroangiographic suite and without general anesthesia for the treatment of spondylytic pain. All procedures utilized pedicle screw fixation, harvesting of local bone autograft, and application of bone fusion material. RESULTS: In this series of 13 patients, a statistically significant reduction of pain was seen at both the 2-week post-operative timepoint, as well as at the time of longest follow-up (mean 40 weeks). DISCUSSION: The advanced and rapid imaging capabilities afforded by a neuroangiographic suite can be safely combined with percutaneous fusion techniques so as to allow for fusion therapies to be applied to patients where the avoidance of general anesthesia is desirable. PMID- 27683707 TI - Effects of cement augmentation on the mechanical stability of multilevel spine after vertebral compression fracture. AB - BACKGROUND: Studies on the effects of cement augmentation or vertebroplasty on multi-level spine after vertebral compression fractures are lacking. This paper seeks to establish a 3-vertebrae ovine model to determine the impact of compression fracture on spine biomechanics, and to discover if cement augmentation can restore mechanical stability to fractured spine. METHODS: Five lumbar spine segments (L1-L3) were obtained from 5-year-old female Merino sheep. Standardized wedge-compression fractures were generated in each L2 vertebra, and then augmented with polymethyl methacrylate (PMMA) cement mixed with 30% barium sulphate powder. Biomechanical pure moment testing in axial rotation (AR), flexion/extension (FE) and lateral bending (LB) was carried out in the intact, fractured and repaired states. Range of motion (ROM) and neutral zone (NZ) parameters were compared, and plain radiographs taken at every stage. RESULTS: Except for a significant increase in ROM between the intact and fractured states in AR between L1 and L2 (P<0.05), there were no other significant differences in ROM or NZ between the other groups. There was a trend towards an increase in ROM and NZ in all directions after fracture, but this did not reach significance. Normal biomechanics was only minimally restored after augmentation. CONCLUSIONS: Results suggest that cement augmentation could not restore mechanical stability of fractured spine. Model-specific factors may have had a role in these findings. Caution should be exercised when applying these results to humans. PMID- 27683710 TI - Cervical disc herniation as a trigger for temporary cervical cord ischemia. AB - BACKGROUND: Disc herniations are only reported in few case reports as a rare cause of acute spinal ischemia. A surgical treatment has not been described so far in these reports with analysis of diffusion weighted magnetic resonance imaging (DWI/MRI) before and after surgery. The aim of our study is to report a case of cervical spinal cord ischemia caused by cervical disc herniation and discuss the literature concerning diagnostic and treatment options. METHODS: A 72 year-old female patient developed an acute progressive tetraparesis with emphasis on the upper extremities. MRI showed a disc herniation at the cervical segment 5/6 (C5/6) with consecutive spinal canal stenosis and additional signs of spinal cord ischemia in T2-weighted imaging (T2WI) and DWI reaching from C3 to C5 level. With the MRI being highly suggestive for anterior spinal cord ischemia, we hypothesized that this might be caused by compression of the anterior spinal artery through the significant disc herniation. Therefore, we decided to perform an anterior discectomy and fusion at C5/6 level. RESULTS: Following surgery, the patient's symptoms showed immediate regression with complete recovery after two months in correspondence with the normalization in the control MRI scan of cervical cord. CONCLUSIONS: Assumedly our patient suffered from a partial anterior spinal artery syndrome, possibly caused by a disc herniation-related compression that was reversible following surgery. This was accompanied by a complete resolution of spinal cord signal abnormalities in T2WI and DWI. PMID- 27683709 TI - Variables associated with remission in spinal surgical site infections. AB - BACKGROUND: There is few medical literature regarding factors associated with remission after surgical and medical treatment of postoperative spine infections. METHODS: Single-centre case-control study 2007-2014. Cluster-controlled Cox regression model with emphasis on surgical and antibiotic-related parameters. RESULTS: Overall, we found 66 episodes in 48 patients (49 episodes with metalwork) who had a median follow-up of 2.6 years (range, 0.5 to 6.8 years). The patients had a median of two surgical debridements. The median duration of antibiotic therapy was 8 weeks, of which 2 weeks parenteral. Clinical recurrence after treatment was noted in 13 episodes (20%), after a median interval of 2 months. In 53 cases (80%), the episodes were considered as in remission. By multivariate analyses, no variable was associated with remission. Especially, the following factors were not significantly related to remission: number of surgical interventions [hazard ratio (HR) 0.9; 95% confidence interval (CI), 0.8-1.1]; infection due to Staphylococcus aureus (HR 0.9; 0.8-1.1), local antibiotic therapy (HR 1.2; 0.6-2.4), and, duration of total (HR 1.0; 0.99-1.01) (or just parenteral) (HR 1.0; 0.99-1.01) antibiotic use. CONCLUSIONS: In patients with post-operative spine infections, remission is achieved in 80%. The number of surgical debridement or duration of antibiotic therapy shows no association with recurrence, suggesting that individual risk factors might be more important than the duration of antibiotic administration. PMID- 27683711 TI - Clinical presentation and surgical outcomes of an intramedullary C2 spinal cord cavernoma: a case report and review of the relevant literature. AB - BACKGROUND: The spinal cord intramedullary cavernoma (SCIC) is a rare form of hemangioma that typically behaves as a space-occupying lesion resulting in neurological symptoms, including bladder and bowel dysfunction. To date, there have been few reports characterizing the clinical presentations and surgical outcomes of cavernomas at the C2 spinal level or the potential for resolution of bladder and bowel symptoms postoperatively. This case details the clinical course of a patient with a C2 cavernoma with an atypical neurological presentation and rapid improvement in both bladder and bowel function postoperatively. This case reviews the relevant literature and describes the patient's clinical presentation, radiological and pathological findings and post-surgical progress. METHODS: A 56-year-old male presented with sensory changes in his right hand, which rapidly progressed over ensuing weeks to bilateral sensory changes in the upper and lower limbs, gait imbalance, urinary and faecal incontinence and loss of temperature perception. He subsequently developed significant weakness in the upper limbs. A MRI identified a hematoma in the cervical cord at the C2 level. Given his rapid neurological decline and the social and clinical implications of his bladder and bowel instability, a surgical approach to therapy was adopted. RESULTS: Postoperatively, there was steady improvement in motor and sensory function and a complete return of bladder and bowel function. CONCLUSIONS: Intramedullary spinal cord cavernomas, although rare, can cause significant neurological deficits and morbidity. Surgical excision can provide significant benefits, including restoration of bladder and bowel function. PMID- 27683712 TI - Fusion in degenerative spondylolisthesis: how to reconcile conflicting evidence. PMID- 27683713 TI - Point of view: a randomized, controlled trial of fusion surgery for lumbar spinal stenosis-lessons learnt and practical considerations. PMID- 27683714 TI - A novel strategy of non-fusion instrumentation with coflex interlaminar stabilization after decompression for lumbar spinal stenosis. PMID- 27683715 TI - Fusion surgery for lumbar spinal stenosis? PMID- 27683726 TI - Systemic resistance in citrus to Tetranychus urticae induced by conspecifics is transmitted by grafting and mediated by mobile amino acids. AB - Recent research suggests that systemic signalling and communication between roots and leaves plays an important role in plant defence against herbivores. In the present study, we show that the oviposition of the two-spotted spider mite Tetranychus urticae in the systemic leaves of citrus rootstock Citrus aurantium (sour orange) was reduced by 50% when a lower leaf was previously infested with conspecifics. Metabolomic and gene expression analysis of the root efflux revealed a strong accumulation of glutamic acid (Glu) that triggered the expression of the citrus putative glutamate receptor (GRL) in the shoots. Additionally, uninfested sour orange systemic leaves showed increased expression of glutamate receptors and higher amounts of jasmonic acid (JA) and 12-oxo phytodienoic acid in plants that were previously infested. Glu perception in the shoots induced the JA pathway, which primed LOX-2 gene expression when citrus plants were exposed to a second infestation. The spider mite-susceptible citrus rootstock Cleopatra mandarin (C. unshiu) also expressed systemic resistance, although the resistance was less effective than the resistance in sour orange. Surprisingly, the mobile signal in Cleopatra mandarin was not Glu, which suggests a strong genotype-dependency for systemic signalling in citrus. When the cultivar Clemenules (C. clementina) was grafted onto sour orange, there was a reduction in symptomatic leaves and T. urticae populations compared to the same cultivar grafted onto Cleopatra mandarin. Thus, systemic resistance is transmitted from the roots to the shoots in citrus and is dependent on rootstock resistance. PMID- 27683729 TI - Effects of curcumin in experimental diabetic nephropathy. AB - Diabetic nephropathy (DN) is currently well established as the most common cause of end-stage renal disease in most parts of the world. Notwithstanding the expanding basic and clinical research in this field, the pathogenesis remains far from clear and hence the treatment of DN remains suboptimal. There is a critical need for the development of newer therapeutic strategies including alternative and complementary therapies. One of the natural products that was extensively studied in cancer and other chronic disease states such as diabetes is curcumin, an active ingredient in turmeric, a spice extensively used in India. In this manuscript, we present a critical review of the experimental and clinical evidence that supports the use of curcumin and its analogs in DN as well as the various proposed mechanisms for its biological actions in health and disease states. PMID- 27683727 TI - The role of OsPT8 in arsenate uptake and varietal difference in arsenate tolerance in rice. AB - Arsenic (As) contamination in paddy soil can cause phytotoxicity and elevated As accumulation in rice grain. Rice varieties vary in As uptake and tolerance, but the underlying mechanisms remain unclear. In this study, the aus variety Kasalath was found to be more tolerant to arsenate [As(V)] than the japonica variety Nipponbare, but the two varieties showed similar arsenite [As(III)] tolerance. Nipponbare took up more phosphate (Pi) and As(V) than Kasalath. The expression of genes for Pi transporters or Pi homeostasis regulation was quantified. Nipponbare showed 2- to 3-fold higher expression of the Pi transporter genes OsPT2 and OsPT8 than Kasalath. Two ospt8 mutants were isolated from the Kasalath background and compared with an ospt8 mutant in the Nipponbare background. Mutation in OsPT8 in both backgrounds decreased As(V) uptake by 33-57%, increased As(V) tolerance assayed by root elongation by >100-fold, and abolished the varietal differences in As(V) uptake and tolerance. The results show that OsPT8 plays a key role in As(V) uptake and that As(V) uptake mediated by OsPT8 exerts a profound toxic effect on root elongation. The results also suggest that differential OsPT8 expression explains the varietal differences in As(V) uptake and tolerance between Kasalath and Nipponbare. PMID- 27683730 TI - Opponent's comments. PMID- 27683728 TI - Interaction between RNA helicase ROOT INITIATION DEFECTIVE 1 and GAMETOPHYTIC FACTOR 1 is involved in female gametophyte development in Arabidopsis. AB - ROOT INITIATION DEFECTIVE 1 (RID1) is an Arabidopsis DEAH/RHA RNA helicase. It functions in hypocotyl de-differentiation, de novo meristem formation, and cell specification of the mature female gametophyte (FG). However, it is unclear how RID1 regulates FG development. In this study, we observed that mutations to RID1 disrupted the developmental synchrony and retarded the progression of FG development. RID1 exhibited RNA helicase activity, with a preference for unwinding double-stranded RNA in the 3' to 5' direction. Furthermore, we found that RID1 interacts with GAMETOPHYTIC FACTOR 1 (GFA1), which is an integral protein of the spliceosome component U5 small nuclear ribonucleoprotein (snRNP) particle. Substitution of specific RID1 amino acids (Y266F and T267I) inhibited the interaction with GFA1. In addition, the mutated RID1 could not complement the seed-abortion phenotype of the rid1 mutant. The rid1 and gfa1 mutants exhibited similar abnormalities in pre-mRNA splicing and down-regulated expression of some genes involved in FG development. Our results suggest that an interaction between RID1 and the U5 snRNP complex regulates essential pre-mRNA splicing of the genes required for FG development. This study provides new information regarding the mechanism underlying the FG developmental process. PMID- 27683731 TI - Opponent's comments. PMID- 27683737 TI - Pandemic Preparedness: Nationally-Led Simulation to Test Hospital Systems. PMID- 27683738 TI - Psychosocial Factors, Knowledge and Attitudes Influencing Skin and Heart Valve Donation among Healthcare Professionals in Singapore. AB - INTRODUCTION: In Singapore, tissue donation is covered under the Medical (Therapy, Education and Research) Act. The objective of this study is to review the demographic and psychosocial factors, which may cause hesitation/unwillingness amongst healthcare professionals towards tissue donation. MATERIALS AND METHODS: A survey comprising 18-items was conducted at the Singapore General Hospital and National Heart Centre Singapore. A total of 521 individuals participated in the survey. Descriptive statistics were performed for the demographic profiles of participants, the factors leading to the support of tissue donation, reasons for hesitation/reluctance to donate tissue and motivating factors to discuss tissue donation with next-of-kin. Pearson's chi square and Fisher's exact tests were employed to assess possible association between various factors and support towards tissue donation. Analyses were performed using Statistical Package for Social Sciences V.21.0 software. RESULTS: A total of 64.9% of participants had heard about skin donation; 48.9% had heard about heart valve donation; 4.5% were tissue pledgers. The primary reason for pro donation was the altruism of "improving someone's quality of life". However, a majority stated they "can decide this in the later part of life" as their main reason for hesitation; 82.3% were willing to discuss their tissue donation wish with next-of-kin, while 53.1% were likely to make the decision of donation on behalf of their deceased next-of-kin. CONCLUSION: RESULTS highlighted important psychosocial and professional factors that influence the hesitation/ reluctance towards donation. Hence, there is a need to re-strategise educational efforts in accordance with the target audiences and address specific misconceptions and concerns. PMID- 27683739 TI - Impact of Direct Cardiovascular Laboratory Activation by Emergency Physicians on False-Positive Activation Rates. AB - INTRODUCTION: Door-to-balloon (DTB) time is critical to ST elevation myocardial infarction (STEMI) patients' survival. Although DTB time is reduced with direct cardiovascular laboratory (CVL) activation by emergency physicians, concerns regarding false-positive activation remain. We evaluate false-positive rates before and after direct CVL activation and factors associated with false-positive activations. MATERIALS AND METHODS: This is a retrospective single centre study of all emergency CVL activation 3 years before and after introduction of direct activation in July 2007. False-positive activation is defined as either: 1) absence of culprit vessel with coronary artery thrombus or ulceration, or 2) presence of chronic total occlusion of culprit vessel, with no cardiac biomarker elevations and no regional wall abnormalities. All false-positive cases were verified by reviewing their coronary angiograms and patient records. RESULTS: A total of 1809 subjects were recruited; 84 (4.64%) identified as false-positives. Incidence of false-positive before and after direct activation was 4.1% and 5.1% respectively, which was not significant (P = 0.315). In multivariate logistic regression analysis, factors associated with false-positive were: female (odds ratio (OR): 2.104 [1.247-3.548], P = 0.005), absence of chest pain (OR: 5.369 [3.024-9.531], P <0.0001) and presence of only left bundle branch block (LBBB) as indication for activation (OR: 65.691 [19.870-217.179], P <0.0001). CONCLUSION: Improvement in DTB time with direct CVL activation by emergency physicians is not associated with increased false-positive activations. Factors associated with false-positive, especially lack of chest pain or LBBB, can be taken into account to optimise STEMI management. PMID- 27683740 TI - Focal Nodular Hashimoto's Thyroiditis: Comparison of Ultrasonographic Features with Malignant and Other Benign Nodules. AB - INTRODUCTION: Hashimoto's thyroiditis (HT) can present as focal nodular disease. This study aimed to determine the distinguishing sonographic features of nodules in biopsy-proven focal HT. MATERIALS AND METHODS: The study included 388 thyroid nodules from 310 patients who underwent ultrasound-guided fine-needle aspiration biopsy (FNAB). There were 28 focal HT, 27 malignant and 333 other benign nodules. Sonographic features of focal HT nodules on prebiopsy ultrasound were compared with malignant nodules and other benign nodules using multinomial logistic regression adjusting for the correlation between multiple nodules obtained from the same patient. RESULTS: Most focal HT nodules were purely solid (92.8%), iso hyperechoic (70.4%), had regular margins (75.0%) and central vascularity (85.7%). Hypoechogenicity (29.6% vs 42.3%; P = 0.017) and microcalcifications (3.6% vs 44.4%; P = 0.003) were significantly less common in focal HT than malignant nodules. None of the focal HT nodules demonstrated marked hypoechogenicity, irregular margins or cervical lymphadenopathy, which are traditionally associated with malignancy. Compared to other benign nodules, focal HT nodules were significantly more likely to be purely solid (92.8% vs 49.0%; P = 0.016), ill defined (25.0% vs 7.0%; P = 0.004) and lack comet-tail artefacts (92.9% vs 66.1%; P = 0.012), which in combination were 17.9% sensitive and 94.6% specific for focal HT. CONCLUSION: Awareness of the above-described sonographic appearances of focal HT may aid in differentiating them from malignant nodules and risk-stratify for FNAB. While there is substantial overlap with other benign nodules, a combination of the above-mentioned 3 ultrasound features is highly specific for focal HT and can prompt further serological evaluation in clinically unsuspected HT. PMID- 27683733 TI - Pediatric low-grade gliomas: implications of the biologic era. AB - For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management. Molecular-targeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown. PMID- 27683741 TI - Use of Prediction Models for Risk Analysis and Decision-Making in Public Health The Catch-22 Conundrum. PMID- 27683742 TI - Reply to "Use of Prediction Models for Risk Analysis and Decision-Making in Public Health-The Catch-22 Conundrum". PMID- 27683743 TI - Comparison of the Haemodynamic Parameters of Venous and Arterial Coronary Artery Bypass Conduits. PMID- 27683744 TI - Circulating Microparticle Double-Stranded Deoxyribonucleic Acid in Systemic Lupus Erythematosus. PMID- 27683745 TI - Lumbar Radiculopathy - Incremental Value of Magnetic Resonance Neurography over Non-Contributory Magnetic Resonance Imaging. PMID- 27683746 TI - Diffuse Indurated Skin. PMID- 27683747 TI - Detection of obstructive uropathy and assessment of differential renal function using two functional magnetic resonance urography tools. A comparison with diuretic renal scintigraphy in infants and children. AB - AIM: After detection of obstructive uropathy (OU), the indication for or against surgery is primarily based on the differential renal function (DRF). This is to compare functional magnetic resonance urography (fMRU) with dynamic renal scintigraphy (DRS) to assess OU and DRF in infants and children. PATIENTS, METHODS: Retrospective analysis in 30 patients (female: 16; male: 14; median age: 5.5 years [0.2-16.5]), divided into subgroup A (age: 0-2 years; n = 16) and B (> 2-17 years; n = 14). fMRU was assessed by measuring renal transit time (RTT) and volumetric DRF with CHOP fMRU tool (CT) and ImageJ MRU plug-in (IJ). OU detection by fMRU was compared with DRS (standard of reference) using areas under the curves (AUC) in ROC analyses. Concordant DRF was assumed if absolute deviation between fMRU and DRS was <= 5 %. RESULTS: DRS confirmed fixed OU in 4/31 kidneys (12.9 %) in subgroup A. AUC of CT was 0.94 compared with 0.93 by IJ. Subgroup B showed fixed OU in 1/21 kidneys (4.8 %) with AUCs of 0.98 each. RTT measured neither by CT nor by IJ in confirmed fixed OU was < 1200 s - resulting in negative predictive values of 1.0 each. In subgroup A, DRF was concordant in 81.3 % of the kidneys for CT and DRS compared with 75.0 % for IJ and DRS. In subgroup B, CT and DRS were concordant in 91.7 %, and IJ and DRS in 45.8 % of the kidneys. CONCLUSION: fMRU accurately excluded fixed OU in infants and children, independent from the software used for quantification. However, assessment of DRF with fMRU deviated from DRS especially in infants who may profit most from early intervention. Thus, fMRU cannot fully replace DRS as primary functional examination. If, for clinical reasons, fMRU is performed in first place and it cannot exclude fixed OU, it should be followed by DRS for validation and DRF quantification. PMID- 27683749 TI - IL-10-Modulated Human Dendritic Cells for Clinical Use: Identification of a Stable and Migratory Subset with Improved Tolerogenic Activity. AB - Dendritic cells (DCs) are key regulators of protective immune responses and tolerance to (self-)Ags. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of allergies, autoimmunity, and transplantation medicine is strong. In this study, we analyzed the tolerogenic capacity of IL-10-modulated DC (IL-10DC) subpopulations to identify a DC subset that combines potent immunosuppressive activities with valuable immune properties for clinical implementation. IL-10DCs consist of two phenotypically distinct subpopulations: CD83highCCR7+ IL-10DCs and CD83lowCCR7- IL-10DCs. Suppressor assays with activated effector T cells revealed that CD4+ regulatory T cells generated by CD83high IL-10DCs (iTreg+) exhibited a significantly higher suppressive capacity compared with CD4+ regulatory T cells generated by CD83low IL-10DCs (iTreg-). In this context, iTreg+ displayed a more activated phenotype (proliferation, cytokine production) compared with iTreg- In contrast to CD83low IL-10DCs, CD83high IL-10DCs exerted a strong migratory capacity toward the secondary lymphoid organ chemokine CCL21 and retained a functionally stable phenotype under inflammatory conditions. In addition, CD83high IL-10DCs expressed significantly higher levels of surface and soluble CD25. Functional analysis demonstrated that IL-10DC-related soluble CD25 efficiently inhibited the proliferation of activated T cells and that blockade of CD25 function abolished the induction of regulatory T cells by IL-10DCs, indicating a critical role for IL-10DC-related CD25 in shifting the immune response toward an iTreg- controlled tolerance reaction. In conclusion, the selective use of the CD83high IL-10DC subset may result in a higher efficacy of tolerance induction in vivo and may support the development of novel DC vaccination strategies for transplantations, as well as for allergic and autoimmune diseases. PMID- 27683748 TI - Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance. AB - Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80+CD11b+ cells overlaps with other leukocytes and that CD45+CD64+ is specific for ATM. The expression of core dendritic cell genes was enriched in CD11c+CD64- cells (ATDC), whereas core macrophage genes were enriched in CD45+CD64+ cells (ATM). CD11c+CD64- ATDCs expressed MHC class II and costimulatory receptors, and had similar capacity to stimulate CD4+ T cell proliferation as ATMs. ATDCs were predominantly CD11b+ conventional dendritic cells and made up the bulk of CD11c+ cells in adipose tissue with moderate high-fat diet exposure. Mixed chimeric experiments with Ccr2-/- mice demonstrated that high-fat diet-induced ATM accumulation from monocytes was dependent on CCR2, whereas ATDC accumulation was less CCR2 dependent. ATDC accumulation during obesity was attenuated in Ccr7-/- mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45+CD64+ ATM and CD45+CD64-CD11c+ ATDCs were identified in human obese adipose tissue and ATDCs were increased in s.c. adipose tissue compared with omental adipose tissue. These results support a revised strategy for unambiguous delineation of ATM and ATDC, and suggest that ATDCs are independent contributors to adipose tissue inflammation during obesity. PMID- 27683751 TI - A Tetravalent Formulation Based on Recombinant Nucleocapsid-like Particles from Dengue Viruses Induces a Functional Immune Response in Mice and Monkeys. AB - Despite the considerable effort that has been invested in elucidating the mechanisms of protection and immunopathogenesis associated with dengue virus infections, a reliable correlate of protection against the disease remains to be found. Neutralizing Abs, long considered the prime component of a protective response, can exacerbate disease severity when present at subprotective levels, and a growing body of data is challenging the notion that their titers are positively correlated with disease protection. Consequently, the protective role of cell-mediated immunity in the control of dengue infections has begun to be studied. Although earlier research implicated cellular immunity in dengue immunopathogenesis, a wealth of newer data demonstrated that multifunctional CD8+ T cell responses are instrumental for avoiding the more severe manifestations of dengue disease. In this article, we describe a new tetravalent vaccine candidate based on recombinant dengue virus capsid proteins, efficiently produced in Escherichia coli and purified using a single ion-exchange chromatography step. After aggregation to form nucleocapsid-like particles upon incubation with an oligodeoxynucleotide containing immunostimulatory CpG motifs, these Ags induce, in mice and monkeys, an IFN-gamma-secreting cell response that significantly reduces viral load after challenge without the contribution of antiviral Abs. Therefore, this new vaccine candidate may not carry the risk for disease enhancement associated with Ab-based formulations. PMID- 27683750 TI - High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5alpha-Restrictive Macaques. AB - We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env) specific Ab, but it did decrease the expression of the gut-homing receptor alpha4beta7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env specific IgA (p = 0.01) and IgG (p < 0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus macaques subgrouped by tripartite motif-containing protein 5alpha (TRIM5alpha) genotypes that are restrictive or permissive for infection by the challenge virus SIVsmE660. Eight of nine TRIM5alpha-restrictive animals receiving no or the lowest dose (1 * 105 PFU) of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5alpha-permissive group, only 1 of 12 animals resisted all 12 challenges. In the TRIM5alpha-restrictive animals, but not in the TRIM5alpha permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r = +0.6) and IgA (r = +0.6), the avidity of Env-specific serum IgG (r = +0.5), and Ab dependent cell-mediated virus inhibition (r = +0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that 1) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of TRIM5alpha restriction, 2) nonneutralizing Ab responses contribute to protection against SIVsmE660 in TRIM5alpha-restrictive animals, and 3) high doses of codelivered MVA/GM-CSF inhibit mucosal Ab responses and the protection elicited by MVA expressing noninfectious SIV macaque 239 virus like particles. PMID- 27683752 TI - Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcgamma Receptors. AB - Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcgammaRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcgammaRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. PMID- 27683754 TI - Use of aspirin as sole oral antiplatelet therapy in acute flow diversion for ruptured dissecting aneurysms. AB - Subarachnoid hemorrhage secondary to rupture of a circumferential dissecting aneurysm continues to be a treatment dilemma. Vessel sacrifice, when possible, continues to be the safest option but in certain cases this is not possible due to lack of collateral supply. In such cases, coil assisted endovascular flow diversion has become a potential option but the requirement for dual antiplatelet therapy in an unsecured intracranial aneurysm continues to raise concern.We present a 48-year-old man with a World Federation of Neurological Surgeons grade 5 subarachnoid hemorrhage, secondary to a ruptured intradural left vertebral artery dissecting aneurysm, who was treated successfully with a pipeline embolization device with Shield technology using aspirin and a single intravenous loading dose of abciximab. To our knowledge, this is the first case of an acute flow diversion performed using only aspirin as the sole oral antiplatelet agent. PMID- 27683753 TI - IL-33 Precedes IL-5 in Regulating Eosinophil Commitment and Is Required for Eosinophil Homeostasis. AB - Eosinophils are important in the pathogenesis of many diseases, including asthma, eosinophilic esophagitis, and eczema. Whereas IL-5 is crucial for supporting mature eosinophils (EoMs), the signals that support earlier eosinophil lineage events are less defined. The IL-33R, ST2, is expressed on several inflammatory cells, including eosinophils, and is best characterized for its role during the initiation of allergic responses in peripheral tissues. Recently, ST2 expression was described on hematopoietic progenitor subsets, where its function remains controversial. Our findings demonstrate that IL-33 is required for basal eosinophil homeostasis, because both IL-33- and ST2-deficient mice exhibited diminished peripheral blood eosinophil numbers at baseline. Exogenous IL-33 administration increased EoMs in both the bone marrow and the periphery in wild type and IL-33-deficient, but not ST2-deficient, mice. Systemic IL-5 was also increased under this treatment, and blocking IL-5 with a neutralizing Ab ablated the IL-33-induced EoM expansion. The homeostatic hypereosinophilia seen in IL-5 transgenic mice was significantly lower with ST2 deficiency despite similar elevations in systemic IL-5. Finally, in vitro treatment of bone marrow cells with IL-33, but not IL-5, led to specific early expansion of IL-5Ralpha expressing precursor cells. In summary, our findings establish a basal defect in eosinophilopoiesis in IL-33- and ST2-deficient mice and a mechanism whereby IL-33 supports EoMs by driving both systemic IL-5 production and the expansion of IL 5Ralpha-expressing precursor cells. PMID- 27683755 TI - Remote aspiration thrombectomy in large vessel acute ischemic stroke. AB - The use of balloon guide catheters in acute ischemic stroke intervention has been associated with improved reperfusion rates and clinical outcomes. This technique acts by promoting flow arrest and subsequent reversal to capture the thrombus debris that may be generated during the clot retrieval process. However, to the best of our knowledge, the use of BGC to remotely aspirate and remove intracranial thrombus has not been previously described. We report a three case series of patients with acute ischemic stroke from supraclinoidal internal carotid artery occlusions treated with remote aspiration thrombectomy through a BGC placed at the cervical internal carotid artery, leading to complete reperfusion without the need for intracranial catheterization. Remote thrombectomy in the setting of intracranial internal carotid artery occlusion may constitute a relatively fast and inexpensive initial thrombectomy maneuver. Further investigation is warranted. PMID- 27683757 TI - Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment. AB - Platelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA<1 month patients. Platelets obtained from ASA>2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1-independent mechanism. PMID- 27683756 TI - Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults. AB - Protein Z (PZ) is a vitamin K-dependent plasma protein that exhibits both pro- and anticoagulant properties. Both low and high PZ levels have been linked to ischaemic stroke. Although PZ-lowering gene variants have been found to be less common in ischaemic stroke, the relationship remains unclear. We investigated PZ levels and PROZ variants in a multi-ethnic case-control study of unexplained stroke in participants aged 18 to 64. Plasma PZ was measured in cases (>=2 months post-stroke) and controls. PZ polymorphisms G79A (rs3024735) and A13G (2273971) were genotyped. A combined genetic score (0-4 minor alleles) was created assuming additive effects. A total of 715 individuals (1:1.4 cases:controls) was included. Analyses revealed evidence of a non-linear association. After adjusting for demographic and clinical covariates, PZ levels >2.5 ug/ml (90th %ile) were significantly associated with cryptogenic stroke (OR 2.41 [95 % CI 1.34, 4.34]) as compared with lower levels. Higher genetic score was related to progressively lower levels of PZ, and the presence of four minor alleles was associated with lower odds of stroke (adjusted OR 0.26 [95 % CI 0.07, 0.96]) versus 0 minor alleles. In this multi-ethnic study of young and middle-aged adults, there was evidence of a non-linear positive association between PZ level and unexplained stroke, with a directionally consistent association for genetic variants related to PZ levels and cryptogenic stroke. These findings support elevated PZ levels as a risk factor for cryptogenic stroke. PMID- 27683759 TI - A novel platelet-type von Willebrand disease mutation (GP1BA p.Met255Ile) associated with type 2B "Malmo/New York" von Willebrand disease. AB - Interaction between von Willebrand factor (VWF) and platelet GPIbalpha is required for primary haemostasis. Lack or loss-of-function in the ligand-receptor pair results in bleeding complications. Paradoxically, gain-of-function mutations in VWF or GPIbalpha also result in bleeding complications as observed in type 2B von Willebrand disease (VWD) and platelet-type- (PT-) VWD, respectively. A similar phenotype is observed with increased ristocetin-induced platelet agglutination and disappearance of the highest molecular weight multimers of VWF. We evaluated a patient with a bleeding disorder and a biological presentation compatible with type 2B VWD. VWF and platelet functional assays, sequencing of the VWF and GP1BA genes, and expression studies in HEK cells were performed. Sequencing of the VWF gene in the propositus revealed a heterozygous p.Pro1266Leu mutation previously found in type 2B VWD Malmo/New York. These variants are characterised by a mild phenotype and a normal VWF multimer composition suggesting the presence of a second mutation in our propositus. Sequencing of the GP1BA gene revealed a heterozygous c.765G>A substitution changing Met at position 255 of GPIbalpha to Ile. This new mutation is located in the beta-switch domain where five other gain-of-function mutations have been reported in PT-VWD. Expression of GPIbalpha Ile255 in HEK GPIb-IX cells resulted in enhanced VWF binding compared to wild-type, similar to known PT-VWD mutations (p.Val249, p.Ser249 and p.Val255) indicating that it contributes to the propositus defects. This first report associating PT- with type 2B VWD illustrates the importance of combining biological assays with genetic testing to better understand the clinical phenotype. PMID- 27683760 TI - Pathophysiological relevance of macrophage subsets in atherogenesis. AB - Macrophages are highly heterogeneous and plastic cells. They were shown to play a critical role in all stages of atherogenesis, from the initiation to the necrotic core formation and plaque rupture. Lesional macrophages primarily derive from blood monocyte, but local macrophage proliferation as well as differentiation from smooth muscle cells have also been described. Within atherosclerotic plaques, macrophages rapidly respond to changes in the microenvironment, shifting between pro- (M1) or anti-inflammatory (M2) functional phenotypes. Furthermore, different stimuli have been associated with differentiation of newly discovered M2 subtypes: IL-4/IL-13 (M2a), immune-complex (M2b), IL-10/glucocorticoids (M2c), and adenosine receptor agonist (M2d). More recently, additional intraplaque macrophage phenotypes were also recognized in response to CXCL4 (M4), oxidized phospholipids (Mox), haemoglobin/haptoglobin complexes (HA-mac/M(Hb)), and heme (Mhem). Such macrophage polarization was described as a progression among multiple phenotypes, which reflect the activity of different transcriptional factors and the cross-talk between intracellular signalling. Finally, the distribution of macrophage subsets within different plaque areas was markedly associated with cardiovascular (CV) vulnerability. The aim of this review is to update the current knowledge on the role of macrophage subsets in atherogenesis. In addition, the molecular mechanisms underlying macrophage phenotypic shift will be summarised and discussed. Finally, the role of intraplaque macrophages as predictors of CV events and the therapeutic potential of these cells will be discussed. PMID- 27683758 TI - Combination therapy for inhibitor reversal in haemophilia A using monoclonal anti CD20 and rapamycin. AB - Development of antibodies (inhibitors) against coagulation factor VIII (FVIII) is a major complication of intravenous replacement therapy in haemophilia A (HA). Current immune tolerance induction (ITI) regimens are not universally effective. Rituximab, a B cell-depleting antibody against CD20, has shown mixed results for inhibitor reversal in patients. This study aims to develop a combinatorial therapy for inhibitor reversal in HA, using anti-murine CD20 (anti-mCD20) antibody and rapamycin, which targets both B and T cell responses. Additionally, it extensively characterises the role of the IgG backbone in B cell depletion by anti-CD20 antibodies. For this, inhibitors were generated in BALB/c-HA mice by weekly IV injection of FVIII. Subsequently, anti-mCD20 (18B12) with IgG2a or IgG1 backbone was injected IV in two doses three weeks apart and B cell depletion and recovery was characterised. Rapamycin was administered orally 3x/week (for 1 month) while continuing FVIII injections. Altering the IgG backbone of anti-mCD20 from IgG2a to IgG1 reduced overall depletion of B cells (including memory B cells), and marginal zone, B-10, and B-1b cells were specifically unaffected. While neither antibody was effective alone, in combination with rapamycin, anti mCD20 IgG2a but not IgG1 was able to reverse inhibitors in HA mice. This regimen was particularly effective for starting titres of ~10 BU. Although IgG1 anti mCD20 spared potentially tolerogenic B cell subsets, IgG2a directed sustained hyporesponsiveness when administered in conjunction with rapamycin. This regimen represents a promising treatment for inhibitor reversal in HA, as both of these compounds have been extensively used in human patients. PMID- 27683761 TI - Young platelets out-of-control. PMID- 27683762 TI - A simplified table for staging embryos of the pipid frog Pipa arrabali. AB - Pipa is a Neotropical genus of frogs that dwell in freshwater environments. It includes four species that lack free-swimming larvae (P. aspera, P. arrabali, P. pipa, and P. snethlageae) and three with tadpoles (P. carvalhoi, P. myersi, and P. parva). Developmental tables such as the one proposed by Nieuwkoop and Faber might be useful for Pipa species with tadpoles. However, for the other Pipa species, to determine stages by this table or by any of the tables already prepared for frogs without tadpoles (e.g., Crinia nimbus, Eleutherodactylus coqui, and Oreobates barituensis) is impossible. By using embryonic, juvenile, and subadult specimens, we generated a staging table for P. arrabali, from the moment limb buds were first observed until birth, based on diagnostic features such as snout-vent length; growth, morphology, and reabsorption of the external tail; growth and differentiation of fore and hind limbs; development of intestine and vent tube; position of the angle of the mouth relative to nostrils and eyes; and color of preserved individuals. Based on these observations, we discuss some noteworthy traits (e.g., posture of hands and feet). We also compare the pattern of development of P. arrabali with that of other anuran species (with and without tadpoles). PMID- 27683763 TI - The effects of forest-savanna-grassland gradients on bird communities of Chiquitano Dry Forests domain, in western Brazil. AB - Different vegetation types are distributed in mountains according to altitude, topography and soil. The composition and structure of bird communities in these areas can change in relation to the vegetation gradient, with particular communities occupying each habitat type. In this study we present the changes in composition, species richness and bird abundance over the gradient of forests, savannas and altitudinal grasslands of Macico do Urucum, a mountainous region located in the Chiquitano Dry Forests domain in western Brazil. We recorded 165 bird species through qualitative and quantitative methods. Forested savannas, riparian forests and submontane forests presented the highest richness and abundance of birds, while arboreal savannas and altitudinal grasslands had intermediate and low values, respectively. The bird composition was similar between riparian and submontane forests, while other vegetation types present more dissimilar bird communities. Our results show differences in composition, richness and bird abundance among the vegetation types present at Macico do Urucum, and highlight an important function of vegetation gradients for the conservation of bird communities in mountains. Additionally, this is the first study of the bird communities in the Brazilian Chiquitano Dry Forests, an important domain in the west of Brazil which has been poorly studied. PMID- 27683764 TI - THE IMPORTANCE OF BRAZILIAN SOCIETY OF METABOLIC AND BARIATRIC SURGERY AND ITS INTERACTION WITH THE XXI WORLD CONGRESS OF IFSO IN BRAZIL. PMID- 27683765 TI - IMPROVEMENT IN OXIDATIVE STRESS AFTER DUODENOJEJUNOSTOMY IN AN EXPERIMENTAL MODEL OF TYPE 2 DIABETES MELLITUS. AB - Background:: Type 2 Diabetes Mellitus is a multifactorial syndrome with severe complications. Oxidative stress is accepted as a causal factor of chronic complications. Aim:: To demonstrate alterations in oxidative stress after metabolic surgery. Methods:: Twenty-four 2-day-old Wistar rats were used. In 16, Type 2 Diabetes Mellitus was induced by 100 mg/kg streptozotocin injection. The development of diabetes was confirmed after 10 weeks using an oral glucose tolerance test. Eight diabetic rats composed the diabetic surgical group; the remaining eight composed the diabetic group. Eight animals in which diabetes was not induced formed the clinical control group. The Marchesini technique was used in the diabetic surgical group. After 90 days, the rats were sacrificed, and the oxidative stress markers were measured. Results:: Thiobarbituric acid reactive substances, superoxide dismutase and catalase were significantly reduced in the diabetic surgical group compared to the diabetic group. Conclusion:: The duodenojejunostomy was effective in controlling the exacerbated oxidative stress present in diabetic rats. Racional:: Diabete melito tipo 2 e sindrome multifatorial com complicacoes graves. O estresse oxidativo e aceito como um fator causal de complicacoes cronicas. Objetivo:: Demonstrar alteracoes no estresse oxidativo apos a cirurgia metabolica. Metodos:: Foram utilizados 24 ratos Wistar de dois dias de idade. Em 16, diabete melito tipo 2 foi induzida por 100 mg/kg de injecao de estreptozotocina. O desenvolvimento do diabete foi confirmado apos 10 semanas, utilizando teste oral de tolerancia a glucose. Oito ratos diabeticos compuseram o grupo cirurgico diabetico; os oito restantes constituiram o grupo diabetico. Oito animais em que nao foi induzido o diabete formaram o grupo controle clinico. A tecnica de Marchesini foi utilizada no grupo cirurgico diabetico. Apos 90 dias, os ratos foram sacrificados, e os marcadores de estresse oxidativo foram medidos. Resultados:: Acido tiobarbiturico, superoxido dismutase e catalase foram significativamente reduzidos no grupo cirurgico diabetico quando comparado ao grupo diabetico. Conclusao:: O duodenojejunostomia foi eficaz no controle do estresse oxidativo exacerbado presente em ratos diabeticos. PMID- 27683766 TI - LINEA ALBA COLLAGEN ASSESSMENT IN MORBIDLY OBESE PATIENTS. AB - Background:: The evaluation of collagen in the abdominal wall has been increasingly studied because of the relevance on collagen in the healing process after laparotomy. Aim:: To evaluate the amount of collagen in the linea alba of patients undergoing laparotomic bariatric surgery and comparing with non-obese cadavers. Methods:: Were evaluated 88 samples of aponeurosis from abdominal linea alba of 44 obese patients (obesity group) and 44 non-obese cadavers (control group). The samples were collected in 2013 and 2104, and were sorted according to age (18-30, 31-45 and 46-60), gender, BMI, waist and cervical circumference, and subcutaneous tissue thickness. Material for biopsy was collected from the supraumbilical region of the linea alba for immunohistochemical analysis differentiating collagen type 1 and type 3 and the 1/3 ratio. Image-Pro Plus pixel counting software was used to measure the amount of collagen. Results:: The obesity group evidenced mean age 44.11+/-9.90 years; 18-30 age group had three (6.8%) obese individuals; 31-45 had 22 (50%) and 46-60 had 19 (43.1%). Females were present in 81.8% (n=36); BMI (kg/m2) was 48.81+/-6.5; waist circumference (cm) was 136.761+/-13.55; subcutaneous tissue thickness (cm) 4.873+/-0.916. Considering age groups, gender and BMI, there were statistical differences in all tests when compared with the cadavers. Conclusion:: The amount of collagen in the linea alba above the umbilical region in the morbidly obese patients was smaller than in the non-obese cadavers in the same age group. Racional:: A avaliacao do colageno na parede abdominal e cada vez mais estudada, em virtude da relevancia dele no processo cicatricial apos laparotomia. Objetivo:: Avaliar a quantidade de colageno na linha alba de pacientes submetidos a cirurgia bariatrica e compara-la com a de cadaveres nao-obesos. Metodo:: Foram avaliados dois grupos com total de 88 amostras da aponeurose da linha alba abdominal, divididas em 44 de pacientes obesos (grupo obesidade) com indicacao de cirurgia bariatrica e 44 de cadaveres nao-obesos (grupo controle). As amostras foram retiradas da linha alba abdominal no periodo de 2013 a 2014 e inicialmente foram separadas conforme faixas etarias (18-30, 31-45 e 46-60), genero, medidas de IMC, circunferencia abdominal e cervical e espessura do subcutaneo do individuo. Foi coletado material para biopsia da linha alba supraumbilical para analise imunoistoquimica, diferenciando o colageno tipo I e III e sua relacao de tipo I/III. Utilizou-se o programa de contagem de pixels Image-Pro Plus(r), que mensurou a quantidade do colageno. Resultados:: O grupo obesidade teve idade 44,11+/-9,90 anos, Na faixa etaria de 18-30 anos foram incluidos tres (6,8%) obesos; na de 31-45 anos 22 (50%) e na de 46-60 anos 19 (43,1%). O genero feminino apresentou predominio, com 36 (81,8%) pacientes. O IMC (kg/m2) foi de 48,81+/-6,5; a circunferencia abdominal (cm) foi de 136,761+/-13,55; a espessura do subcutaneo (cm) foi de 4,873+/-0,916. A quantidade de colageno tipo I foi de 134.683,3+/-206.657,4; a de colageno tipo III foi de 413.137,2+/-283.656,1; a razao do colageno tipo I/III foi 0,419+/ 0,636. Considerando-se faixas de idade, genero e IMC, foram constatadas diferencas estatisticas em todas as analises quando comparadas com as dos cadaveres. Conclusao:: Os obesos morbidos apresentaram quantidade de colageno na linha alba supraumbilical menor que a do grupo controle de cadaveres nao-obesos na mesma faixa etaria. PMID- 27683768 TI - EFFECT OF SIZE OF INTESTINAL DIVERSIONS IN OBESE PATIENTS WITH METABOLIC SYNDROME SUBMITTED TO GASTRIC BYPASS. AB - Background:: There is no consensus on the ideal size of intestinal loops in gastric bypass of bariatric surgeries. Aim:: To evaluate the metabolic outcome of patients submitted to gastric bypass with alimentary and biliopancreatic loops of different sizes. Methods: : Was conducted a retrospective cohort study in diabetic obese patients (BMI>=35 kg/m2) with metabolic syndrome submitted to gastric bypass. The patients were divided into three groups according to the size of the intestinal loop: group 1, biliopancreatic limb 50 cm length and alimentary limb 100 cm length; group 2 , biliopancreatic limb 50 cm length and alimentary limb 150 cm length; and group 3, biliopancreatic limb 100 cm length and alimentary limb 150 cm length. The effect of gastric bypass with different sizes of intestinal loops in relation to the parameters that define metabolic syndrome was determined. Results: : Sixty-three patients were evaluated, and they had a mean age of 44.7+/-9.4 years. All were diabetics, with 62 (98.4%) being hypertensive and 51 (82.2%) dyslipidemic. The three groups were homogeneous in relation to the variables. In 24 months, there was a remission of systemic arterial hypertension in 65% of patients in group 1, 62.5% in group 2 and 68.4% in group 3. Remission of diabetes occurred in 85% of patients in group 1, 83% in group 2 and 84% in group 3. There was no statistical difference in %LEW between the groups, and waist measurements decreased in a homogeneous way in all groups. The size of loops also had no influence on the improvement in dyslipidemia. Conclusion: : Variation in size of intestinal loops does not appear to influence improvement in metabolic syndrome in this group of patients. Racional:: Nao ha consenso sobre o tamanho ideal das alcas intestinais no bypass gastrico em Y-de Roux em cirurgias bariatricas. Objetivo:: Avaliar os desfechos metabolicos de pacientes submetidos ao bypass gastrico com alca intestinal alimentar e biliopancreatica de tamanhos diferentes. Metodos: : Realizou-se coorte retrospectiva em pacientes obesos (IMC>=35 kg/m2) diabeticos com sindrome metabolica submetidos ao bypass gastrico em Y-de-Roux. Foram divididos em tres grupos conforme a dimensao das alcas intestinais: grupo 1, alca biliopancreatica de 50 cm e alca alimentar de 100 cm; grupo 2, alca biliopancreatica de 50 cm e alca alimentar de 150 cm e grupo 3, alca biliopancreatica de 100 cm e alca alimentar de 150 cm. Foram avaliados os parametros que compoem a sindrome metabolica. Resultados: : Incluiram-se 63 pacientes, com media de idade de 44.7+/ 9.4 anos. Todos eram diabeticos, 62 (98.4%) hipertensos e 51 (82.2%) dislipidemicos. Os tres grupos eram homogeneos em relacao as variaveis estudadas. Em 24 meses houve remissao da hipertensao arterial sistemica em 65% do grupo 1, 62.5% no grupo 2 e 68.4% no grupo 3. A remissao do diabete melito tipo 2 ocorreu em 85% dos pacientes do grupo 1, 83% no grupo 2, e 84% no grupo 3. Nao houve diferenca estatistica na porcentagem de perda do excesso de peso entre os grupos e as medidas da cintura abdominal reduziram de forma homogenea em todos os grupos. A dimensao das alcas tambem nao influenciou na melhora da dislipidemia. Conclusao: : A variacao da dimensao das alcas intestinais nao influenciou na melhora da sindrome metabolica neste grupo de pacientes. PMID- 27683767 TI - COMPLICATIONS RELATED TO GASTRIC BYPASS PERFORMED WITH DIFFERENT GASTROJEJUNAL DIAMETERS. AB - Background:: Among the options for surgical treatment of obesity, the most widely used has been the Roux-en-Y gastric bypass. The gastrojejunal anastomosis can be accomplished in two ways: handsewn or using circular and linear stapled. The complications can be divided in early and late. Aim:: To compare the incidence of early complications related with the handsewn gastrojejunal anastomosis in gastric bypass using Fouchet catheter with different diameters. Method:: The records of 732 consecutive patients who had undergone the bypass were retrospectively analyzed and divided in two groups, group 1 with 12 mm anastomosis (n=374), and group 2 with 15 mm (n=358). Results:: The groups showed anastomotic stenosis with rates of 11% and 3.1% respectively, with p=0.05. Other variables related to the anastomosis were also analyzed, but without statistical significance (p>0.05). Conclusion:: The diameter of the anastomosis of 15 mm was related with lower incidence of stenosis. It was found that these patients had major bleeding postoperatively and lower surgical site infection, and in none was observed presence of anastomotic leak. Racional: : Entre as opcoes para o tratamento cirurgico da obesidade, o mais utilizado e o bypass gastrico em Y-de Roux. A anastomose gastrojejunal dele pode ser realizada de duas maneiras, manualmente ou utilizando grampeador linear e circular, e as complicacoes sao dividas em precoces e tardias. Objetivo:: Comparar a incidencia de complicacoes precoces relacionadas com a confeccao manual da anastomose gastrojejunal no bypass gastrico utilizando sonda de Fouchet com calibres diferentes. Metodos:: Foi realizada analise retrospectiva transversal com 732 pacientes submetidos ao procedimento, divididos em dois grupos, grupo 1 com anastomose de 12 mm (n=374), e grupo 2 de 15 mm (n=358). Resultados:: Os grupos apresentaram taxas de estenose de anastomose de 11% e 3,1% respectivamente, com p=0,05. Outras variaveis relacionadas a anastomose tambem foram analisadas, porem sem significancia estatistica (p>0,05). Conclusao:: O diametro da anastomose de 15 mm esteve relacionado a menor ocorrencia de estenoses. Verificou-se, contudo, que estes pacientes apresentaram maior sangramento no pos-operatorio e menor infeccao de sitio cirurgico. Nao ocorreram fistulas na presente casuistica. PMID- 27683769 TI - EFFECTS OF LONG-TERM ROUX-EN-Y GASTRIC BYPASS ON BODY WEIGHT AND CLINICAL METABOLIC COMORBIDITIES IN BARIATRIC SURGERY SERVICE OF A UNIVERSITY HOSPITAL. AB - Background:: Due to the high failure rate observed in the clinical treatment of morbid obesity an increase in bariatric surgery indications, as an alternative for the control of obesity and comorbidities, is noticeable. Aim:: To evaluate the performance of type 2 diabetes mellitus, high blood pressure and dyslipidemia in patients submitted to Roux-en-Y gastric bypass in late follow-up. Methods:: Retrospective analysis of 59 patients included in the bariatric surgery program. Anthropometric (height and body weight) and laboratory (LDLc, HDLc, VLDLc, triglyceride -TG - and glucose) data were collected on pre- and postoperative stages, through medical records. Results:: Among the patients, 86% were female aged 43+/-11, of whom 52% had attended high school. The average postoperative time was 7+/-3 years. During the postoperative period, there were decreases of weight and body mass index, respectively (133+/-06 kg vs 91+/-04 kg p<0.05 e 49+/ 74 kg/m2 vs 33+/-79 kg/m2, p<0.05). In comparison to the preoperative stage, lower concentrations of glucose (101.00+/-26.99 vs 89,11+/-15.19, p=0.014), total cholesterol rates (179.00+/-37,95 vs 167.48+/-28,50, p=0.016), LDLc (104.30+/ 33.12 vs 91.46+/-24.58, p=0.016), VLDLc (25.40+/-11,12 vs 15.68+/-7.40, p<0.01), and TG (143.35+/-86.35 vs 82.45+/-37.39, p<0.01) and higher concentrations of HDLc (43.53+/-8.23 vs 57.90+/-15.60, p<0.01) were identified in the postoperative stage. 40% of hypertensive patients were still undergoing high blood pressure treatment during the postoperative stage. There was remission of type 2 diabetes mellitus and dyslipidemia on 81% and 94% of the cases, respectively. Conclusion:: Roux-en-Y gastric bypass has proven itself to be an effective long term procedure, promoting weight loss, remission of DM2 and dyslipidemia. Racional:: Em funcao do alto grau de falencia que se observa no tratamento clinico da obesidade morbida, observa-se um aumento da procura pela cirurgia bariatrica como alternativa para o controle da obesidade e comorbidades. Objetivo:: Avaliar a evolucao do diabete melito tipo 2, da hipertensao arterial sistemica e da dislipidemia em pacientes submetidos a gastroplastia redutora em Y-de-Roux no periodo de pos-operatorio tardio. Metodos:: Analise retrospectiva de 59 pacientes inseridos em programa de cirurgia bariatrica. Foram coletados dados antropometricos (altura e peso corporal) e laboratoriais (LDLc, HDLc, VLDLc, triglicerideo -TG - e glicose) nos periodos pre e pos-operatorio por meio de prontuarios medicos. Resultados:: Entre os pacientes, 86% eram mulheres com idade de 43+/-11 anos e 52% tinham cursado o ensino medio. O tempo medio de pos operatorio foi de 7+/-3 anos. Houve reducao no peso e no indice de massa corporal no pos-operatorio, respectivamente (133+/-06 kg vs 91+/-04 kg p<0,05 e 49+/-74 kg/m2 vs 33+/-79 kg/m2, p<0,05). Observou-se concentracoes inferiores no pos operatorio, comparado com o pre-operatorio, da glicose (101,00+/-26,99 vs 89,11+/ 15,19, p=0,014), colesterol total (179,00+/-37,95 vs 167,48+/-28,50, p=0,016), LDLc (104,30+/-33,12 vs 91,46+/-24,58, p=0,016), VLDLc (25,40+/-11,12 vs 15,68+/ 7,40, p<0,01), e TG (143,35+/-86,35 vs 82,45+/-37,39, p<0,01) e maiores de HDLc (43,53+/-8,23 vs 57,90+/-15,60, p<0,01 ). No pos-operatorio 40% dos pacientes hipertensos ainda estavam em tratamento para hipertensao arterial sistemica. Houve remissao do diabete melito tipo 2 e da dislipidemia em 81% e 94% dos casos, respectivamente. Conclusao:: A gastroplastia redutora em Y-de-Roux mostrou ser procedimento eficaz em longo prazo, com resultados persistentes na perda de peso, remissao do DM2 e da dislipidemia. PMID- 27683770 TI - INTESTINAL MALROTATION IN PATIENTS UNDERGOING BARIATRIC SURGERY. AB - Background:: Intestinal malrotation is a rare congenital anomaly. In adults is very difficult to recognize due to the lack of symptoms. Diagnosis is usually incidental during surgical procedures or at autopsy. Aim:: To review the occurrence and recognition of uneventful intestinal malrotation discovered during regular cases of bariatric surgeries. Methods:: Were retrospectively reviewed the medical registry of 20,000 cases undergoing bariatric surgery, from January 2002 to January 2016, looking for the occurrence of intestinal malrotation and consequences in the intraoperative technique and immediate evolution of the patients. Results:: Five cases (0,025%) of intestinal malrotation were found. All of them were males, aging 45, 49, 37,52 and 39 years; BMI 35, 42, 49, 47 and 52 kg/m2, all of them with a past medical history of morbid obesity. The patient with BMI 35 kg/m2 suffered from type 2 diabetes also. All procedures were completed by laparoscopic approach, with no conversions. In one patient was not possible to move the jejunum to the upper abdomen in order to establish the gastrojejunostomy and a sleeve gastrectomy was performed. In another patient was not possible to fully recognize the anatomy due to bowel adhesions and a single anastomosis gastric bypass was preferred. No leaks or bleeding were identified. There were no perioperative complications. All patients were discharged 72 h after the procedure and no immediate 30-day complications were reported. Conclusion:: Patients with malrotation can successfully undergo laparoscopic bariatric surgery. May be necessary changes in the surgical original strategy regarding the malrotation. Surgeons must check full abdominal anatomical condition prior to start the division of the stomach. Racional: : Ma-rotacao intestinal e rara anomalia congenita em adultos de dificil reconhecimento devido a falta de sintomas. O diagnostico e feito geralmente incidentalmente durante procedimentos cirurgicos ou durante autopsia. Objetivo:: Verificar a ocorrencia e reconhecimento nao eventual da ma-rotacao intestinal durante operacoes bariatricas sequenciais. Metodo:: Retrospectivamente foram analisados os prontuarios medicos de 20.000 casos de operacoes bariatricas de janeiro 2002 a janeiro de 2016, procurando por ocorrencia de ma-rotacao intestinal, sua interferencia na tecnica operatoria aplicada e a evolucao imediata no pos operatorio. Resultados:: Foram encontrados cinco casos (0.025%) de ma-rotacao intestinal em homens com idades de 37, 39, 45, 49 e 52 anos e IMC de 35, 42, 49, 47 e 52 kg/m2. O paciente com IMC de 35 kg/m2 tambem sofria de diabete melito tipo 2. Todos os procedimentos foram realizados atraves de laparoscopia, sem conversoes. Em um paciente nao foi possivel mover o jejuno para o abdome superior a fim de realizar gastrojejunostomia; foi, entao, realizada gastrectomia vertical. Em outro paciente, nao foi possivel reconhecer totalmente a anatomia devido as aderencias intestinais e foi decidido realizar bypass gastrico com anastomose unica. Nenhum vazamento ou sangramento foi identificado. Nao houve nenhuma complicacao pos-operatoria. Todos os pacientes foram liberados 72 h apos o procedimento e nenhuma complicacao foi notificada nos primeiros 30 dias. Conclusoes:: A cirurgia bariatrica laparoscopica pode ser realizada com sucesso em pacientes com ma-rotacao. Mudancas talvez sejam necessarias com relacao a anomalia. Os cirurgioes devem verificar toda a condicao anatomica abdominal antes de iniciar a seccao gastrica. PMID- 27683771 TI - PSYCHOLOGICAL PROFILE OF PATIENTS ELIGIBLE FOR BARIATRIC SURGERY. AB - Background: : The psychologist who works in bariatric surgery has a role to receive, evaluate, prepare and educate the patient who will undergo the surgical procedure. Psychological evaluation becomes important in so far as allows us to obtain data on personal and familiar history and allow tracing of possible psychopathology. Aim: : To collect data on psychological evaluations of patients in a bariatric surgery service of a public hospital in order to describe the psychological profile of patients in this service. Method: : Data were collected from 827 patients between 2001 and 2015, using data from an interview, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Binge Eating Scale (BES). Results: : The mean age of patients before surgery was 39 years+/- 10, the mean BMI was 51 kg/m2+7, and most patients (81%) were female. The average score on the BDI was 14.8+8 and women had significantly higher scores than men. On the BAI the average score was 11+8 and on the ECAP was 14+8, both with no difference between groups. Conclusions: : Psychosocial characteristics of the patients points to the significant presence of indicators of depression, with low levels of anxiety and binge eating. Racional:: O psicologo que atua na area da cirurgia bariatrica tem papel de acolher, avaliar, preparar e conscientizar o paciente que vai ser submetido ao procedimento cirurgico. A avaliacao psicologica reveste-se de importancia na medida em que obtem dados sobre historia pessoal e familiar, alem do rastreio de possiveis alteracoes psicopatologicas. Objetivo: : Analisar as avaliacoes psicologicas dos pacientes de um servico de cirurgia bariatrica de um hospital publico, buscando tracar o perfil psicologico dos pacientes deste servico. Metodos: : Foram coletados dados de 827 pacientes entre 2001 e 2015, utilizando-se dados de uma entrevista, Inventario Beck de Depressao (BDI), Inventario Beck de Ansiedade (BAI) e Escala de Compulsao Alimentar Periodica (ECAP). Resultados: : A idade media dos pacientes antes da operacao foi 39 anos+10 e o IMC medio foi 51 kg/m2+7, sendo a maioria (81%) do genero feminino. A pontuacao media no BDI foi 14,8+8 e as mulheres tiveram pontuacao significativamente maior que os homens. No BAI a pontuacao media foi 11+ 8 e no ECAP 14+ 8, ambos sem diferenca entre os grupos. Conclusao: : A caracterizacao psicossocial dos pacientes avaliados aponta para a presenca significativa de indicadores de depressao, com baixos niveis de ansiedade e de compulsao alimentar. PMID- 27683772 TI - INFLAMMATORY DISORDERS ASSOCIATED WITH HELICOBACTER PYLORI IN THE ROUX-EN-Y BYPASS GASTRIC POUCH. AB - Background: : The prevalence of Helicobacter pylori in obese candidates for bariatric surgery and its role in the emergence of inflammatory lesions after surgery has not been well established. Aim: : To identify the incidence of inflammatory lesions in the stomach after bariatric surgery and to correlate it with H. pylori infection. Methods: : This is a prospective study with 216 patients undergoing Roux-en-Y gastric bypass. These patients underwent histopathological endoscopy to detect H. pylori prior to surgery. Positive cases were treated with antibiotics and a proton inhibitor pump followed by endoscopic follow-up in the 6th and 12th month after surgery. Results: : Most patients were female (68.1%), with grade III obesity (92.4%). Preoperative endoscopy revealed gastritis in 96.8%, with H. pylori infection in 40.7% (88/216). A biopsy was carried out in 151 patients, revealing H. pylori in 60/151, related to signs of inflammation in 90% (54/60). In the 6th and 12th month after surgery, the endoscopy and the histopathological exam showed a normal gastric pouch in 84% of patients and the incidence of H. pylori was 11% and 16%, respectively. The presence of inflammation was related to H. pylori infection (p<0,001). Conclusion:: H. pylori has a similar prevalence in both obese patients scheduled to undergo bariatric surgery and the general population. There is a low incidence of it in the 6th and 12th months after surgery, probably owing to its eradication when detected prior to surgery. When inflammatory disease is present in the new gastric reservoir it is directly related to H. pylori infection. Racional: : Helicobacter pylori e responsavel por varias doencas gastrointestinais. Com o aumento de cirurgia bariatrica no pais, ha poucos estudos sobre a prevalencia desta bacteria em obesos com indicacao cirurgica e o seu papel no surgimento de lesoes inflamatorias no pos-operatorio. Objetivo - : Identificar a incidencia de lesoes inflamatorias no estomago pos-cirurgia bariatrica e correlacionar com a infeccao por H. pylori. Metodos - : Estudo prospectivo com dois grupos de pacientes. Em ambos os grupos verificou-se a prevalencia do H. pylori no pre operatorio atraves de histopatologia, mas em apenas um dos grupos, nos casos de H. pylori positivo realizou-se o tratamento com antibioticoterapia e inibidor de bomba de proton com realizacao de nova endoscopia no 6 degrees e 12 degrees mes pos-operatorio. Resultados: : Avaliou-se 216 pacientes, com as seguintes caracteristicas: sexo feminino (68,1%), faixa etaria entre 30-40 anos, com 31,9% e 31%, respectivamente. De acordo com o IMC, 17,6% apresentavam obesidade moderada, 82,4% obesidade severa/morbida e 9,7% superobesidade. Nos pacientes submetidos a endoscopia, a positividade do H. pylori se manifestou em 40,7%, sendo responsavel pela atividade inflamatoria na mucosa gastrica (p<0,001). No pos-operatorio, investigou-se a mucosa gastrica atraves de endoscopia e histopatologia no 6 degrees e 12 degrees mes, que demonstrou normalidade no neorreservatorio gastrico em 84% dos pacientes, e a incidencia de H. pylori foi 11% aos seis meses e 16% aos 12 meses, sendo a presenca de processo inflamatorio relacionado com a infeccao pela bacteria (p<0,001). Conclusao: - H. pylori apresenta prevalencia similar tanto em obesos que irao submeter-se a cirurgia bariatrica quanto a populacao em geral; ha baixa incidencia dele no 6 degrees e 12 degrees mes apos a operacao e isto deve-se provavelmente a sua erradicacao quando detectado no pre-operatorio; quando presente a doenca inflamatoria no neorreservatorio gastrico possui relacao direta com a infeccao por H. pylori. PMID- 27683773 TI - GASTRIC AND JEJUNAL HISTOPATHOLOGICAL CHANGES IN PATIENTS UNDERGOING BARIATRIC SURGERY. AB - Background:: Morbid obesity is a multifactorial disease that increasingly is being treated by surgery. Aim: : To evaluate gastric histopathological changes in obese, and to compare with patients who underwent gastrojejunal bypass and the jejunal mucosa after the surgery. Methods:: This is an observational study performed at a tertiary public hospital, evaluating endoscopic biopsies from 36 preoperative patients and 35 postoperative. Results:: In the preoperative group, 80.6% had chronic gastritis, which was active in 38.9% (77.1% and 20.1%, respectively, in the postoperative). The postoperative group had a significant reduction in H. pylori infection (p=0.0001). A longer length of the gastric stump and a time since surgery of more than two years were associated with Helicobacter pylori infection. The jejunal mucosa was normal in 91.4% and showed slight nonspecific chronic inflammation in 8.6%. Conclusion:: There was a reduction in the incidence of Helicobacter pylori infection in the postoperative group. A longer length of the gastric stump and longer time elapsed since surgery were associated with Helicobacter pylori infection. The jejunal mucosa was considered normal in an absolute majority of patients. Racional: : A obesidade morbida e doenca multifatorial cujo tratamento cirurgico e cada vez mais indicado. Objetivo: : Avaliar alteracoes histopatologicas gastricas em obesos e comparar com os submetidos a bypass gastrojejunal e a mucosa jejunal apos a operacao. Metodo:: Estudo observacional realizado em hospital publico terciario avaliando biopsias endoscopicas de 36 pacientes no pre-operatorio e 35 no pos-operatorio. Resultados:: No pre-operatorio 80,6% apresentaram gastrite cronica, 38,9% em atividade (77,1% e 20,1%, respectivamente, no pos-operatorio). O grupo pos operatorio apresentou diminuicao significativa na infeccao por Helicobacter pylory (p=0,0001). Maior comprimento do coto gastrico e tempo de operacao superior a dois anos associaram-se a infeccao por Helicobacter pylori. A mucosa jejunal foi normal em 91,4% e apresentava leve inflamacao cronica inespecifica em 8,6%. Conclusao:: Houve diminuicao da infeccao por Helicobacter pylori apos a operacao. Maior comprimento do coto gastrico e do tempo de operacao associaram-se a infeccao por Helicobacter pylori. A mucosa jejunal foi considerada normal na maioria absoluta dos pacientes do grupo pos-operatorio. PMID- 27683774 TI - EVALUATION OF THE THORACOABDOMINAL MOBILITY OF OBESE SUBJECTS IN PRE-BARIATRIC SURGERY. AB - Background:: Obesity can affect the thorax, diaphragm, and alterations in respiratory function even if the lungs are within normality. The respiratory compliance is very reduced by the increase in fat mass. Aim:: To evaluate the effect of the physical therapeutic respiratory exercises on the thoracoabdominal mobility of obese individuals in pre-bariatric surgery. Methods:: Cross-sectional and descriptive study, which used the cirtometry (axillary, xiphoid and abdominal) to evaluate the mobility of 74 individuals, 27 men and 47 women, in pre-bariatric surgery, assisted by the team EMAD, after eight weeks of physiotherapy, following a protocol of exercises, reevaluating and compared the measures pre and post intervention. Results:: Had positive correlation abdominal mobility in the total volume of all participants (p=0.010) and also for all the measures in the measurement of residual volume in three levels (p=0.000). Comparing genders, in total volume, cirtometry abdominal greater for women (p=0.015) when compared to men and residual volume, significance for either men or women in all measurements (p=0.000). Conclusion:: Obese patients that underwent the physiotherapeutic treatment during the preoperative period, had pre respiratory dynamics improved by the increase in the mobility of the chest cavity and by the improvement of respiratory conscience. Racional: : A obesidade pode afetar o torax e o diafragma, determinando alteracoes na funcao respiratoria, mesmo quando os pulmoes se apresentam dentro da normalidade. A complacencia respiratoria e muito reduzida pelo aumento de massa gordurosa. Objetivo:: Avaliar o efeito de exercicios fisioterapeuticos respiratorios sobre a mobilidade toracica de individuos obesos no pre-operatorio de cirurgia bariatrica. Metodo:: Estudo transversal e descritivo, que utilizou a cirtometria (axilar, xifoide e abdominal) para avaliar a mobilidade de 74 individuos, 27 homens e 47 mulheres, em pre-operatorio de cirurgia bariatrica, assistidos pela equipe EMAD, apos oito semanas de fisioterapia, seguindo um protocolo de exercicios, reavaliando e comparado as medidas pre e pos a intervencao. Resultado:: Apresentaram correlacao positiva a mobilidade abdominal no volume total de todos os participantes (p=0,010) e tambem para todas as medidas na mensuracao do volume residual nos tres niveis (p=0,000). Comparando os sexos, no volume total, a cirtometria abdominal maior das mulheres (p=0,015) quando comparada a dos homens e no volume residual, significancia tanto para os homens quanto para as mulheres em todas as mensuracoes (p=0,000). Conclusao:: Obesos que se submeteram ao tratamento fisioterapeutico durante o periodo pre-operatorio, tiveram dinamica respiratoria melhorada pelo aumento da mobilidade da caixa toracica e pela melhora da consciencia respiratoria. PMID- 27683775 TI - POSTOPERATIVE EFFECT OF PHYSICAL THERAPY RELATED TO FUNCTIONAL CAPACITY AND RESPIRATORY MUSCLE STRENGTH IN PATIENTS SUBMITTED TO BARIATRIC SURGERY. AB - Background: : Respiratory physiotherapy plays an important role preventing complications in bariatric surgery. Aim: : To assess the effects of out-patient physiotherapy during post-operative period through respiratory pressures and functional capacity in individuals submitted to bariatric surgery. Method: : A prospective longitudinal and controlled study was done in adults with body mass index (BMI) equal or greater than 40 kg/m2, who have been submitted to bariatric surgery. They were divided into two groups: intervention-group, who performed out patient physiotherapy twice a week, from thirty to sixty days after surgery; and the control-group, who only followed home instructions. Both groups were evaluated before surgery and sixty days after surgery through manovacuometry, six minute walk test and the Borg Scale of perceived exertion. Results:: Twenty participants were included the intervention-group and twenty-three in the control group. Both groups had significant and similar weight loss after surgery. The manovacuometry presented no differences comparing pre- and post-surgery and in the comparison between the groups. The result of the six-minute walk test for the intervention-group increased by 10.1% in the post-operative period in relation to pre-. The Borg scale of perceived exertion in the intervention-group in pre surgery decreased by 13.5% in the post-surgery compared to pre-surgery. In the control-group there was no difference comparing pre- and post-operative values, as in the comparison with the intervention-group. Conclusion: : The low-intensity exercise program, carried out between the 30th and the 60th day after bariatric surgery provided better functional capacity; did not change respiratory muscle strength; and improved the perceived exertion rate. Racional: : A fisioterapia respiratoria tem papel importante na prevencao das complicacoes da cirurgia bariatrica. Objetivo: : Avaliar os efeitos da fisioterapia ambulatorial no pos operatorio atraves das pressoes respiratorias e da capacidade funcional dos individuos submetidos a cirurgia bariatrica. Metodo: : Estudo prospectivo, longitudinal, randomizado e controlado, em adultos com IMC>=40 kg/m2, que se submeteram a cirurgia bariatrica, Foram divididos em dois grupos: grupo intervencao, que realizou fisioterapia ambulatorialmente, duas vezes por semana, do trigesimo ao sexagesimo dia de pos-operatorio; e grupo controle, que seguiu orientacoes domiciliares. Ambos os grupos foram avaliados no pre-operatorio e apos 60 dias da operacao atraves das pressoes respiratorias com a manovacuometria, do teste da caminhada de 6 min e do indice de percepcao de esforcos pela escala de Borg. Resultados: : Foram incluidos 20 participantes no grupo intervencao e 23 no grupo controle, ambos com perda de peso significativa e similar no pos-operatorio. A manovacuometria nao demonstrou diferencas nas pressoes respiratorias na comparacao entre o pre-operatorio e o pos-operatorio e na comparacao entre os grupos. O resultado do teste da caminhada de 6 min para o grupo intervencao aumentou em 10,1% no pos-operatorio em relacao ao pre operatorio. A percepcao de esforco pela escala de Borg no grupo intervencao reduziu em 13,5% no pos-operatorio comparado ao pre. No grupo controle nao foi observada diferenca entre o pre e o pos-operatorio bem como na comparacao com o grupo intervencao. Conclusao: : O programa de exercicios de baixa intensidade realizado entre o 30o e o 60o dia de pos-operatorio de cirurgia bariatrica promoveu melhor capacidade funcional; nao modificou a forca muscular respiratoria; e melhorou o indice de percepcao de esforco. PMID- 27683776 TI - SURFACE ELECTROMYOGRAPHY OF MASSETER AND TEMPORAL MUSCLES WITH USE PERCENTAGE WHILE CHEWING ON CANDIDATES FOR GASTROPLASTY. AB - Background:: Surface electromyography identifies changes in the electrical potential of the muscles during each contraction. The percentage of use is a way to treat values enabling comparison between groups. Aim:: To analyze the electrical activity and the percentage of use of masseter and temporal muscles during chewing in candidates for gastric bypass. Methods:: It was used Surface Electromyography Miotool 200,400 (Miotec (r), Porto Alegre/RS, Brazil) integrated with Miograph 2.0 software, involving patients between 20-40 years old. Were included data on electrical activity simultaneously and in pairs of temporal muscle groups and masseter at rest, maximum intercuspation and during the chewing of food previously classified. Results:: Were enrolled 39 patients (59 women), mean age 27.1+/-5.7. The percentage of use focused on temporal muscle, in a range of 11-20, female literacy (n=11; 47.82) on the left side and 15 (65.21) on the right-hand side. In the male, nine (56.25) at left and 12 (75.00) on the right hand side. In masseter, also in the range of 11 to 20, female literacy (n=10; 43.48) on the left side and 11 (47.83) on the right-hand side. In the male, nine (56.25) at left and eight (50.00) on the right-hand side. Conclusion:: 40-50% of the sample showed electrical activity in muscles (masseter and temporal) with variable values, and after processing into percentage value, facilitating the comparison of load of used electrical activity between the group, as well as usage percentage was obtained of muscle fibers 11-20% values involving, representing a range that is considered as a reference to the group studied. The gender was not a variable. Racional:: A eletromiografia de superficie identifica variacoes dos potenciais eletricos dos musculos durante cada contracao realizada. O percentual de uso e uma forma de tratar valores possibilitando comparacao entre grupos. Objetivo:: Analisar a atividade eletrica e o percentual de uso dos musculos masseteres e temporais durante a mastigacao em candidatos a gastroplastia. Metodos:: Utilizado Eletromiografo de Superficie Miotool 200/400 (Miotec(r), Porto Alegre/RS, Brasil) integrado ao software Miograph 2.0 em pacientes entre 20-40 anos candidatos a gastroplastia. Foram incluidos dados relativos a atividade eletrica simultanea e em pares dos grupos musculares temporais e masseteres em repouso, maxima intercuspidacao habitual e durante mastigacao de alimento previamente classificado. Resultados:: Foram analisados 39 pacientes (59% feminino), media de idade de 27,1+5,7. O percentual de uso se concentrou em musculatura temporal, em faixa de 11-20% no sexo feminino (n=11; 47,82%) referente a lateral esquerda e 15 (65,21%) na lateral direita. No masculino, nove (56,25%) na lateral esquerda e 12 (75,00%) na lateral direita. Em masseteres, tambem na faixa de 11-20% no sexo feminino (n=10; 43,48%) referente a lateral esquerda e 11 (47,83%) na lateral direita. No masculino, nove (56,25%) na lateral esquerda e oito (50,00%) na lateral direita. Conclusao:: Entre 40-50% da amostra houve variacao na atividade eletrica em masseteres e temporais, e, apos transformacao em valor percentual, facilitou-se a comparacao da carga de atividade eletrica utilizada entre o grupo, bem como obteve-se percentual de uso de fibras musculares envolvendo valores de 11-20%, representando uma faixa que se considera como referencial para o grupo estudado. O genero nao constituiu variavel em pacientes obesos morbidos. PMID- 27683777 TI - MASTICATORY FUNCTION OF OBESE CANDIDATES TO BARIATRIC SURGERY FROM DISTINCT SOCIOECONOMIC CLASSES. AB - Background:: Obesity and metabolic syndrome can be labeled as worldwide outbreak; thus, both have led to serious public health problem. Oral health can be worsened by both, obesity and metabolic syndrome. Tooth loss harms masticatory function, essential status to whom will be submitted to bariatric surgery. Aim:: Assess masticatory function of obese candidates to bariatric surgery, who belong to distinct socioeconomic class range, in order to recognize hazard factors and the bias of socioeconomic factor in this context. Methods:: Observational cross section study, with samples comprised by two groups of patients, with distinct socioeconomic class range, one of them belonging to public health system (SUSG) and the other to private clinic (CPG), candidates to bariatric surgery. Were assessed anthropometric data, comorbidities and medicines usage, blood tests, habits and the number of dental functional units. Results:: The groups SUSG and CPG were homogeneous taking into account gender (p=0,890) and age range (p=0,170). The number of dental functional units was higher in the private group (p<0.001). The impaired masticatory function was rather present among public group (p<0.001) and female gender (p<0,001). Regarded as blood tests, fasting glucose was higher in female in SUSG (p<0,001). The following hazard factors have corroborated to have patients rated as impaired masticatory function: belong to public service (OR: 8.420, p=0.003), higher age (OR: 1.186, p<0.001), female gender (OR: 0.153, p=0.029), diabetes mellitus (OR: 2.545, p=0.045) and smokers (OR: 2.951, p=0.043). Conclusion:: The general health and masticatory function of female SUSG were worse, highlighting the socioeconomic condition as hazard factor. Racional:: Obesidade e sindrome metabolica sao graves problemas de saude publica, com caracteristicas de epidemia mundial. A saude bucal e agravada por ambas as condicoes. Perda dentaria prejudica funcao mastigatoria, condicao essencial para o paciente que sera submetido a cirurgia bariatrica. Objetivo:: Avaliar a funcao mastigatoria de pacientes obesos candidatos a cirurgia bariatrica pertencentes a dois servicos de saude com padroes socioeconomicos distintos, afim de identificar fatores de risco e a influencia do fator socioeconomico nesta condicao. Metodos:: Estudo observacional transversal, com amostra constituida por dois grupos de pacientes obesos, com condicoes socioeconomicas distintas, um pertencente ao sistema publico de saude (GSUS) e outro a clinica privada (GCP), candidatos a cirurgia bariatrica. Foram analisados dados antropometricos, comorbidades e uso de medicamentos para seu controle, exames laboratoriais, habitos e o numero de unidades funcionais dentarias presentes. Resultados:: Os grupos GSUS e GCP foram homogeneos quanto ao genero (p=0,890) e faixa etaria (p=0,170). A media de unidades funcionais dentarias foi maior no grupo privado (p<0,001). A funcao mastigatoria prejudicada foi mais presente no grupo GSUS e no genero feminino (p<0,001). Quanto aos exames laboratoriais: glicemia de jejum esteve mais alterada em mulheres do GSUS (p<0,001). Foram fatores de risco independentes para ter funcao mastigatoria prejudicada: ter origem no servico publico de saude (OR: 8,420 - p=0,003), maior idade (OR: 1,186 - p<0,001), ser do genero feminino (OR: 0,153 - p=0,029), portador de diabete melito (OR: 2,545 - p=0,045) e tabagista (OR: 2,951 - p=0,043). Conclusao:: A saude geral e funcao mastigatoria de mulheres do GSUS foram piores, ressaltando a condicao socioeconomica como fator de risco. PMID- 27683778 TI - ASSESSMENT OF BODY FAT IN OBESE PATIENTS PREOPERATIVELY FOR BARIATRIC SURGERY. AB - Background: : The study of body composition in patient candidates for bariatric surgery is directly related to the increase and distribution of body fat in the development of cardiovascular disease. Aim: : To correlate anthropometric indicators and bioelectrical impedance in the assessment of body fat in female candidates for bariatric surgery. Methods:: Cross-sectional, observational study of 88 women. The weight, height, body mass index and waist circumference data were evaluated in the anthropometric analysis. The body fat was determinate by bioelectrical impedance conducted according to the manufacturer's recommended technique with a specific severe obesity formula. The patients were divided into two subgroups according to the average waist circumference and body mass index for better analysis of the results. Results:: The group had a mean age of 39.7 years (+/-7.2), average weight of 125.6 kg (+/-16.2), mean body mass index of 48.7 kg/m2 (+/-6.4) and the mean waist circumference 137.6 cm (+/-12.4). Negative and significant relationship between BMI values waist circumference and resistance obtained by bioelectrical impedance were found. By analyzing the two groups the mean BMI and waist circumference, a significant relationship was observed, ie, the higher the degree of obesity less resistance was obtained by bioelectrical impedance. The higher is the obesity the lower is value found for resistance. Conclusion:: The increase of anthropometric indicators (BMI and waist circumference) determined reduction in resistance and reactance obtained by bioelectrical impedance analysis in obese women candidates to bariatric surgery. Racional:: O estudo da composicao corporal em pacientes candidatas a cirurgia bariatrica tem relacao direta com o aumento e distribuicao da gordura corporal e no desenvolvimento de doencas cardiovasculares. Objetivo:: Estudar a correlacao entre indicadores antropometricos e da bioimpedancia eletrica na avaliacao da gordura corporal em mulheres candidatas a cirurgia bariatrica. Metodos:: Estudo transversal, observacional com 88 pacientes. Na analise antropometrica foram avaliados os dados de peso, altura, IMC e circunferencia da cintura. Para bioimpedancia eletrica utilizou-se a tecnica recomendada pelo fabricante do aparelho e formula especifica para obeso grave na determinacao da gordura corporal. Para melhor analise dos resultados as pacientes foram divididas em dois subgrupos de acordo com a media de circunferencia da cintura e IMC. Resultados: : O grupo apresentou media de idade 39,7 anos (+/-7,2), media de peso 125,6 kg (+/ 16,2), media de IMC 48,7 kg/m2 (+/-6,4) e media de circunferencia da cintura 137,6 cm (+/-12,4). Foram encontradas relacoes negativas e significativas entre os valores de IMC, circunferencia da cintura e a resistencia obtida atraves da bioimpedancia eletrica. Ao analisar os dois subgrupos de valores medios de IMC e circunferencia da cintura, observou-se relacao significativa, ou seja, quanto maior o grau de obesidade menor e a resistencia obtida atraves da bioimpedancia eletrica. Conclusao:: O aumento dos indicadores antropometricos (IMC e circunferencia da cintura) determinaram reducao nas variaveis resistencia e reatancia obtidas pela bioimpedancia eletrica em mulheres candidatas a cirurgia bariatrica. PMID- 27683779 TI - SERUM VITAMIN B12, IRON AND FOLIC ACID DEFICIENCIES IN OBESE INDIVIDUALS SUBMITTED TO DIFFERENT BARIATRIC TECHNIQUES. AB - Background:: Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Aim:: Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. Methods:: A retrospective analysis was performed using the electronic charts of patients submitted to bariatric surgery involving adjustable gastric banding and Roux-en-Y gastric bypass at the Sao Joao Hospital Center in the city of Porto, Portugal, between 2005 and 2010. The following data were collected: surgical technique, sex, age, marital status, serum concentrations of vitamin B12, iron and folic acid and postoperative lifestyle. A 5% significance level was used for the statistical analysis (p<0.05). Results:: Among 286 individuals evaluated, females accounted for 90.9% of the overall sample (both techniques). Gastric banding was performed more (68.9%), but greater nutrient deficiencies were found following gastric bypass. Iron was the most prevalent deficiency (21.3%), followed by vitamin B12 (16.9%) and folic acid (4.5%). Mild to moderate alcohol intake, adherence to the diet and the use of multivitamins reduced the frequency, but did not avoid micronutrient deficiency. Conclusion: : Vitamin B12, iron and folic acid deficiencies were found in the first and second year following the two bariatric techniques analyzed and were more frequent among individuals submitted to gastric bypass. Racional:: As diferentes tecnicas da cirurgia da obesidade combinam ma absorcao com procedimentos restritivos e podem levar a complicacoes metabolicas, entre as quais se destacam as deficiencias de micronutrientes. Objetivo:: Avaliar a deficiencia de vitamina B12, ferro e acido folico e fatores associados ao estilo de vida de obesos submetidos a diferentes tecnicas cirurgicas. Metodos:: Analise retrospectiva dos prontuarios eletronicos de pacientes submetidos a cirurgia bariatrica pelas tecnicas de banda gastrica ajustavel e bypass gastrico em Y-de Roux, no Centro Hospitalar de Sao Joao, E.P.E., Porto - Portugal, no periodo de 2005-2010. Foram coletadas: tecnica cirurgica, sexo, idade, estado civil, concentracoes sericas de vitamina B12, ferro e acido folico e o estilo de vida no pos-operatorio. Para analise estatistica foi utilizado nivel de significancia de 5% (p< 0,05). Resultados:: Dentre os 286 individuos avaliados, houve predominio do sexo feminino (90,9%) em ambas as tecnicas cirurgicas, sendo a banda gastrica a mais realizada (68,9%); no entanto maiores deficiencias de micronutrientes foram detectadas apos o bypass gastrico. A deficiencia de micronutriente mais prevalente foi a de ferro (21,3%), seguida da vitamina B12 (16,9%) e do acido folico (4,5%). A ingestao de bebida alcoolica de leve-moderada, a adesao a dieta e o uso de polivitaminicos reduziu a frequencia, mas nao evitou a carencia de micronutrientes. Conclusao: : A deficiencia de vitamina B12, ferro e acido folico foi observada durante o primeiro e o segundo anos apos as duas tecnicas avaliadas, sendo mais frequente nos pacientes submetidos ao bypass gastrico. PMID- 27683780 TI - PRE- AND POSTOPERATIVE IN BARIATRIC SURGERY: SOME BIOCHEMICAL CHANGES. AB - Background:: The bariatric surgery may cause some nutritional deficiencies. Aim: : To compare the serum levels of biochemical markers, in iimmediate post-surgical patients who were submitted to bariatric surgery. Methods: : Non-concurrent prospective cross-sectional study. The analysis investigated data in medical charts of pre-surgical and immediate post-surgical patients who were submitted to bariatric surgery, focusing total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C reactive protein, vitamin B12 levels, folic acid, homocysteine values, iron and serum calcium at the referred period. Results: : Twenty-nine patients of both genders were evaluated. It was observed weight loss from 108.53 kg to 78.69 kg after the procedure. The variable LDL-c had a significant difference, decreasing approximately 30.3 mg/dl after the surgery. The vitamin B12 serum average levels went from 341.9 pg/ml to 667.2 pg/ml. The triglycerides values were in a range of 129.6 mg/dl-173.3 mg/dl, and 81.9 mg/dl-105.3 mg/dl at the pre- and postoperative respectively. CRP levels fall demonstrated reduction of inflammatory activity. The variable homocysteine was tested in a paired manner and it did not show a significant changing before or after, although it showed a strong correlation with LDL cholesterol. Conclusion: : Eligible patients to bariatric surgery frequently present pre-nutritional deficiencies, having increased post-surgical risks when they don't follow an appropriate nutritional follow-up. Racional: : A cirurgia bariatrica pode causar deficiencias nutricionais. Objetivo: : Comparar os niveis sericos bioquimicos de pacientes submetidos a cirurgia bariatrica no pre e pos-operatorio precoce. Metodos: : Estudo transversal, retrospectivo nao concorrente. A analise considerou a investigacao de prontuarios de pacientes submetidos a gastroplastia no periodo pre-operatorio e pos-operatorio precoce, analisando resultado bioquimicos de colesterol total, HDL colesterol, LDL colesterol, triglicerides, proteina C reativa, dosagens de vitamina B12, acido folico, valores de homocisteina, ferro e calcio sericos, no referido periodo. Resultados: : Compuseram a amostra 29 pacientes de ambos os sexos. Houve reducao de peso apos o procedimento cirurgico com media de 108,53 kg para 78,69 kg. A variavel LDL-c apresentou diferenca significativa com diminuicao de aproximadamente 30,3 mg/dl apos a gastroplastia. Com relacao a media de niveis sericos de vitamina B12 ela passou de 341,9 pg/ml para 667,2 pg/ml. Os valores de triglicerides encontravam-se na faixa de 129,6 mg/dl-173,3 mg/dl, e 81,9 mg/dl-105,3 mg/dl no pre e pos-cirurgico, respectivamente. Foi evidenciada reducao da atividade inflamatoria verificada mediante queda dos niveis de PCR. A variavel homocisteina foi avaliada de maneira pareada e nao apresentou mudanca significativa no antes e depois, havendo, contudo, forte correlacao com o LDL-colesterol. Conclusao: : Pacientes candidatos a cirurgia bariatrica frequentemente apresentam deficiencias nutricionais anteriores ao procedimento com riscos aumentados no periodo pos-cirurgico quando nao aderem ao acompanhamento nutricional adequado. PMID- 27683781 TI - EARLY POSTOPERATIVE COMPLICATIONS IN ROUX-EN-Y GASTRIC BYPASS. AB - Background: : Roux-en-Y gastric bypass is one of the most common bariatric surgery and leads to considerable weight loss in the first months. Aim: : To quantify the main early postoperative complications in patients submitted to the gastric bypass. Method: : Observational retrospective cohort. Data of 1051 patients with class II obesity associated with comorbidities or class III obesity submitted to the gastric bypass with 30 days of follow-up starting from the date of the surgery. Results:: The age average was 36 years with a predominance of females (81.1%). The mean preoperative body mass index was 43 kg/m2. The major complication was fistula (2.3%), followed by intestinal obstruction (0.5%) and pulmonary embolism (0.5%). Death occurred in 0.6% of the cases. Conclusion:: In the period of 30 days after surgery the overall complication rate was 3.8%; reoperation was necessary in 2.6% and death occurred in 0.6%. Fistula was the main complication and the leading cause of hospitalization in intensive care unit, reoperation and death. Racional:: Bypass gastrico em Y-de-Roux e uma das operacoes bariatricas mais comuns e leva a perdas consideraveis de peso ja nos primeiros meses. Objetivo:: Quantificar as principais complicacoes pos operatorias precoces em pacientes submetidos ao bypass gastrico. Metodo:: Coorte retrospectiva observacional. Amostra de 1051 pacientes portadores de obesidade grau II associada a comorbidades ou grau III submetidos ao bypass gastrico com acompanhamento de 30 dias a partir da data da operacao. Resultados:: A idade media dos pacientes foi de 36 anos com predominancia de mulheres (81,1%). O indice de massa corporal pre-operatorio medio foi de 43 kg/m2. A principal complicacao foi fistula (2,3%), seguida de obstrucao intestinal (0,5%) e tromboembolismo pulmonar (0,5%). Obito ocorreu em 0,6% dos casos. Conclusao:: No periodo de 30 dias de pos-operatorio a taxa geral de complicacoes foi de 3,8%; a de reoperacao de 2,6% e obito em 0,6%. A fistula foi a principal complicacao e a principal causa de internamento em unidade de terapia intensiva, de reoperacao e de obito. PMID- 27683782 TI - KNEE ARTHROSCOPIC VISIBILITY ALTERATIONS IN OBESE AND NON-OBESE PATIENTS. AB - Background:: Obesity is a chronic disease and has become the most prevalent public health problem worldwide. The impact of obesity on knee is strong and the BMI is correlated with the different alterations. Aim:: Compare surgical visualization of arthroscopic field in partial meniscectomy in obese and non obese. Method:: Sixty patients were selected, 30 obese and 30 non-obese who underwent arthroscopic partial meniscectomy. The arthroscopic surgical procedures were recorded and analyzed. For the analysis of visualization was used the Johnson's classification (2000). Results:: Were analyzed 48 men and 12 women, the average age was 42.9 years with BMI between 21.56 to 40.14 kg/m2. The distribution of visibility of the surgical field according to the classification was: grade 1 - 38/60 (63.3%); grade 2 - 13/60 (21.6%); grade 3 - 6/60 (10%); grade 4 - 3/60 (5%). Conclusion:: Knee arthroscopy did not show a significant difference in the visibility of arthroscopic field in obese and non-obese patients. Thus, it should not be indicated as the preferred method of diagnostic evaluation of joint changes in these patients. Racional: : A obesidade e doenca cronica e tem se tornado o problema de saude publica mais prevalente em todo mundo. O impacto dela no joelho e grande e o IMC esta correlacionado com as diferentes alteracoes existentes. Objetivo: : Comparar a visualizacao do campo videoartroscopico na meniscectomia parcial de joelho em pacientes obesos e nao obesos. Metodo: : Foram selecionados 60 pacientes, sendo 30 obesos e 30 nao obesos que realizaram meniscectomia parcial videoartroscopica. Os procedimentos videoartroscopicos foram gravados e posteriormente analisados. Foi utilizada na analise a classificacao de visibilidade do campo videoartroscopico de Johnson (2000). Resultados: : Foram analisados 48 homens e 12 mulheres com idade media de 42,9 anos e IMC de 21,56 a 40,14 kg/m2. A distribuicao da visibilidade do campo cirurgico foi: grau 1 - 38/60 (63,3%); grau 2 - 13/60 (21,6%); grau 3 - 6/60 (10%); grau 4 - 3/60 (5%). Conclusao:: A artroscopia de joelho nao demonstrou diferenca significativa quanto a visualizacao do campo videoartroscopico em pacientes obesos e nao obesos. Desta forma, nao deve ser indicada como metodo preferencial de avaliacao diagnostica das alteracoes articulares nesses pacientes. PMID- 27683783 TI - SAFETY AND EFFECTIVENESS OF SINGLE ANASTOMOSIS DUODENAL SWITCH PROCEDURE: PRELIMINARY RESULT FROM A SINGLE INSTITUTION. AB - Background:: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) was introduced into bariatric surgery by Sanchez-Pernaute et al. as an advancement of the biliopancreatic diversion with duodenal switch. Aim:: To evaluate the SADI-S procedure with regard to weight loss, comorbidity resolution, and complication rate in the super obese population. Methods: : A retrospective chart review was performed on initial 72 patients who underwent laparoscopic or robot-assisted laparoscopic SADI-S between December 17th, 2013 and July 29th, 2015. Results: : A total of 48 female and 21 male patients were included with a mean age of 42.4+/-10.0 years (range, 22-67). The mean body mass index (BMI) at the time of procedure was 58.4+/-8.3 kg/m2 (range, 42.3-91.8). Mean length of hospital stay was 4.3+/-2.6 days (range, 3-24). Thirty-day readmission rate was 4.3% (n=3), due to tachycardia (n=1), deep venous thrombosis (n=1), and viral gastroenteritis (n=1). Thirty-day reoperation rate was 5.8% (n=4) for perforation of the small bowel (n=1), leakage (n=1), duodenal stump leakage (n=1), and diagnostic laparoscopy (n=1). Percentage of excess weight loss (%EWL) was 28.5+/ 8.8 % (range, 13.3-45.0) at three months (n=28), 41.7+/-11.1 % (range, 19.6-69.6) at six months (n=50), and 61.6+/-12.0 % (range, 40.1-91.2) at 12 months (n=23) after the procedure. A total of 18 patients (26.1%) presented with type II diabetes mellitus at the time of surgery. Of these patients, 9 (50.0%) had their diabetes resolved, and six (33.3%) had it improved by 6-12 months after SADI-S. Conclusions: : SADI-S is a feasible operation with a promising weight loss and diabetes resolution in the super-obese population. Racional: : Anastomose unica em bypass duodenoileal com gastrectomia vertical (SADI-S) foi introduzida na cirurgia bariatrica por Sanchez-Pernaute et al. como um avanco da derivacao biliopancreatica com switch duodenal. Objetivo:: Avaliar o procedimento SADI-S no que diz respeito a perda de peso, resolucao de comorbidades e taxa de complicacoes na populacao de superobesos. Metodos:: Estudo retrospectivo com 72 pacientes iniciais que foram submetidos a laparoscopia ou por robo-assistida SADI S laparoscopica entre 17 de dezembro de 2013 e 29 de Julho de 2015. Resultados:: Foram incluidos 48 pacientes do sexo feminino e 21 do masculino com media idade de 42,4+/-10,0 anos (variacao, 22-67). O indice de massa corporal (IMC) no momento do procedimento foi de 58,4+/-8,3 kg/m2 (42,3-91,8). O tempo medio de permanencia hospitalar foi de 4,3+/-2,6 dias (3-24). A taxa de readmissao em 30 dias foi de 4,3% (n=3), devido a taquicardia (n=1), trombose venosa profunda (n=1), e gastroenterite viral (n=1). A taxa de reoperacao em 30 dias foi de 5,8% (n=4) para a perfuracao do intestino delgado (n=1), fistula (n=1), deiscencia do coto duodenal (n=1), e laparoscopia de diagnostico (n=1). Percentagem de excesso de perda de peso (% PEP) foi de 28,5+/-8,8% (13,3-45,0) em tres meses (n=28), 41,7+/-11,1% (19,6-69,6) em seis meses (n=50), e 61,6+/-12,0% (40,1-91,2) aos 12 meses (n=23) apos o procedimento. Um total de 18 pacientes (26,1%) apresentou-se com diabete melito tipo 2, no momento da operacao. Desses, nove (50,0%) tiveram seu diabete resolvido, e seis (33,3%) tinham melhorado em 6-12 meses apos SADI-S. Conclusoes:: SADI-S e operacao viavel com promissora perda de peso e de resolucao do diabete melito na populacao de superobesos. PMID- 27683785 TI - SIMPLIFIED LAPAROSCOPIC GASTRIC BYPASS WITH GASTROJEJUNAL LINEAR MECHANICAL ANASTOMOSIS: TECHNICAL ASPECTS. AB - Background:: Gastric bypass is a restrictive and malabsorptive surgery. The restrictive part consists in the creation of a small gastric pouch. The gastrointestinal bypass serves as the malabsorptive element. Aim: : To describe a simplified gastric bypass approach for morbid obese patients, showing our results, and also remarking the importance of this technique for reducing the learning curve. Method:: The patient is positioned in a split legs position and carefully strapped to the operating room table, with the surgeon between the patient's legs. Five trocars are inserted after pneumoperitoneum at the umbilicus. Dissection of the esophagogastric angle and lesser curvature is mandatory before the gastric pouch manufacturing. This pouch is done with two blue load staplers. Using a blue load linear stapler inserted only half way into the hole in the pouch is used to perform the gastrojejunal anastomosis and in order to create an anastomosis that is about 2 cm in length. A side-to-side jejunojejunostomy is done with a white load linear stapler. The last step of the gastric bypass consists in the cut of the jejunum between the two anastomosis with a white load linear stapler. Blue test is performed in order to detect leaks. Results: : From January 2012 to December 2015, 415 simplified RYGB were performed. Gender: 67% female and 33 % males. Average of BMI 44.7. Mean age was 42 years old. Mean operative time 79 min. 39 % of this sample had T2 diabetes. Regarding complications were observed, one fistula, one gastrojejunal stenosis and one obstruction due to a bezoar. Conclusion: : The described technique is a simplified approach in which all the anastomosis are performed in the upper part of the abdomen, allowing the surgeons to be more systematized and avoiding them to make mistakes in the confection of the Roux-en-Y anastomosis. This simplified gastric bypass is a safe and reproducible technique. Racional: : Bypass gastrico e cirurgia restritiva e malabsortiva. A parte restritiva consiste na criacao de uma pequena bolsa gastrica. O bypass gastrointestinal serve como o elemento malabsortivo. Objetivo: : Descrever uma abordagem de bypass gastrico simplificado para pacientes obesos morbidos, mostrando os resultados, e tambem destacando a importancia desta tecnica para reduzir a curva de aprendizagem. Metodo: : O paciente e posicionado em posicao de pernas abertas e cuidadosamente amarrado a mesa da sala de operacao com o cirurgiao entre as pernas. Cinco trocarteres sao inseridos apos pneumoperitonio no umbigo. Disseccao do angulo esofagogastrico e curvatura menor e obrigatoria antes da realizacao da bolsa gastrica. Esta bolsa e feita com dois grampeadores de carga azuis. Usando um grampeador carga linear azul inserido apenas a meio caminho para dentro do orificio na bolsa e executada a anastomose gastrojejunal a fim de criar anastomose de cerca de 2 cm de comprimento. Jejunojejunostomia laretolateral e feita com um grampeador carga linear branca. A ultima etapa do bypass gastrico consiste no corte do jejuno entre as duas anastomoses com um grampeador carga linear branco. Teste de azul e realizado de modo a detectar vazamentos. Resultados: : De janeiro de 2012 a dezembro de 2015, foram realizadas 415 RYGB simplificadas. Genero: 67% homens e 33% mulheres. A media do IMC foi de 44,7 e a de idade 42 anos. A media de tempo operatorio foi de 79 min. 39% desta amostra tinha diabete melito tipo 2. Quanto as complicacoes foram observadas uma fistula, uma estenose gastrojejunal e uma obstrucao devido a bezoar. Conclusao: : A tecnica descrita e uma abordagem simplificada, na qual todas as anastomoses sao realizadas na parte superior do abdome, permitindo aos cirurgioes serem mais sistematizados e evitando cometerem erros na confeccao da anastomose em Y-de-Roux. Este bypass gastrico simplificado e tecnica segura e reprodutivel. PMID- 27683784 TI - SADI-S WITH RIGHT GASTRIC ARTERY LIGATION: TECHNICAL SYSTEMATIZATION AND EARLY RESULTS. AB - Background:: Bariatric surgery is performed all over the world with close to 500.000 procedures per year. The most performed techniques are Roux-en-Y gastric bypass and sleeve gastrectomy. Despite this data, the most effective procedure, biliopancreatic diversion with or without duodenal switch, represents only no more than 1.5% of the procedures. Technical complexity, morbidity, mortality, and severe nutritional adverse effects related to the procedure are the main fears that prevent most universal acceptance. Aim:: To explain the technical aspects and the benefits of the SADI-S with right gastric artery ligation as an effective simplification from the original duodenal switch. Methods:: Were included all patients undergoing this procedure from the November 2014 to May 2016, describing and analysing aspects of this technique, the systematization and early complications associated with the procedure. Results:: A series of 67 patients were operated; 46 were women (68.7%); mean age of the group was 44 years old (33 56); and an average BMI of 53.5 kg/m2 (50-63.5). Surgical time was 115 min (80 180). A total of five patients (7.5%) had any complication and two (2.9%) had to be reoperated. There were two patients with leak, one at the duodenal stump and other at the esophagogastric angle. There was no mortality. Patients stayed at the hospital a median of 2.5 days (1-25). Conclusions:: SADI-S with right gastric artery ligation is a safe procedure with few preliminary complications. The technical variations introduced to the classical duodenal switch are reproducible and may allow this procedure to be more popular. All the complications in this series were not related to the ligation of the right gastric artery. Racional:: Cerca de 500.000 cirurgias bariatricas sao realizadas a cada ano em todo o mundo. As tecnicas mais realizadas sao o bypass gastrico em Y-de-Roux e a gastrectomia vertical. A derivacao biliopancreatica, com ou sem duodenal switch, e considerada tecnica mais eficaz no tratamento cirurgico do paciente obeso morbido; entretanto, representa nao mais do que 1,5% dos procedimentos na atualidade, pois sua complexidade tecnica, morbimortalidade e graves efeitos adversos nutricionais impedem aceitacao mais universal. Objetivo:: Descrever os aspectos tecnicos e os beneficios do SADI-S com ligadura da arteria gastrica direita como um modo simplificado do duodenal switch original. Metodos:: Foram incluidos todos os pacientes submetidos a este procedimento entre novembro 2014 e maio de 2016. Alem da descricao da sistematizacao da tecnica operatoria, foram analisadas as complicacoes precoces associadas ao procedimento. Resultados:: Uma serie de 67 pacientes foi operada no periodo analisado; 46 eram mulheres (68,7%) e a media de idade foi de 44 anos (33-56). O IMC medio foi de 53,5 kg/m2 (50-63,5). O tempo cirurgico medio foi de 115 min (80-180) e a permanencia hospitalar media foi de 2,5 dias (1-25). Complicacoes foram observadas em cinco pacientes (7,5%) e dois (2,9%) tiveram de ser reoperados. Duas pacientes evoluiram com fistula, uma no coto duodenal e outra na juncao esofagogastrica. Nao houve mortalidade. Conclusao:: SADI-S com ligadura da arteria gastrica direita e procedimento seguro com poucas complicacoes precoces. A simplificacao tecnica em relacao ao duodenal switch classico pode permitir que este procedimento se torne mais popular. Todas as complicacoes observadas nesta serie nao estavam relacionadas com a ligadura da arteria gastrica direita. PMID- 27683786 TI - ENDOSCOPIC SLEEVE GASTROPLASTY - MINIMALLY INVASIVE THERAPY FOR PRIMARY OBESITY TREATMENT. AB - Background: : Less invasive and complex procedures have been developed to treat obesity. The successful use of Endoscopic Sleeve Gastroplasty using OverStitch(r) (Apollo Endosurgery, Austin, Texas, USA) has been reported in the literature. Aim: : Present technical details of the procedure and its surgical/ endoscopic preliminary outcome. Method: : The device was used to perform plications along the greater curvature of the stomach, creating a tubulization similar to a sleeve gastrectomy. Result:: A male patient with a BMI of 35.17 kg/m2 underwent the procedure, with successful achievement of four plications, and preservation of gastric fundus. The procedure was successfully performed in 50 minutes, time without bleeding or other complications. The patient presented mild abdominal pain and good acceptance of liquid diet. Conclusions: : The endoscopic gastroplasty procedure was safe, with acceptable technical viability, short in duration and without early complications. Racional: : Procedimentos menos invasivos e complexos tem sido desenvolvidos para o tratamento da obesidade. A gastroplastia vertical endoscopica com uso de OverStitch(r) (Apollo Endosurgery, Austin, TX, EUA) ja foi relatada com sucesso na literatura. Objetivo: : Apresentar detalhes tecnicos do procedimento e seu resultado cirurgico/endoscopico preliminar. Metodo: : O equipamento foi utilizado para realizar plicaturas ao longo da grande curvatura gastrica, objetivando tubulizacao do estomago semelhante a gastrectomia vertical. Resultado: : O metodo foi aplicado em paciente com IMC 35,17 kg/m2, sendo realizadas quatro plicaturas, preservando o fundo gastrico. O procedimento foi realizado com sucesso em 50 min, sem sangramento ou outras complicacoes. O paciente evoluiu com dor abdominal leve, e teve boa aceitacao de dieta liquida. Conclusao: : A realizacao da gastroplastia endoscopica foi segura, com viabilidade tecnica aceitavel e reprodutivel, com curto tempo de procedimento, sem complicacoes precoces. PMID- 27683787 TI - PROPOSAL OF A REVISIONAL SURGERY TO TREAT SEVERE NUTRITIONAL DEFICIENCY POST GASTRIC BYPASS. AB - Background: The gastric bypass has nutritional and electrolyte disturbances rate of approximately 17%. The most common deficits are protein malnutrition, ferric and zinc, in addition to the vitamin. Although rare, some malnutrition stages reach such severity that ends up being necessary hospitalization and sometimes revisional or reversal surgical procedures. Aim: : To present a proposal of surgical revision for treatment of severe malnutrition after bariatric surgery. Methods: : The procedure is to reconstitute the food transit through the duodenum and proximal jejunum, keeping the gastric bypass restrictive component. As an additional strategy, the gastric fundus resection is performed, aiming to intensify the suppression of the greline and avoiding excessive weight regain. Results: : After initial stabilization, nutritional and electrolytic support, the procedure was performed in two patients as definitive treatment of malnutrition status. Good results were observed at one year follow up. Conclusion: : As improvement option and/or resolution of the nutritional alterations, surgical therapy is one of the alternatives. There is still no consensus on the surgical technique to be performed. This procedure is based on pathophysiological factors for the treatment of this condition, with good initial results, without significant clinical alterations. Longer follow-up will determine its effectiveness. Racional: : O bypass gastrico consta com taxa de disturbios nutricionais e eletroliticos de aproximadamente 17%. Os deficits mais frequentes sao a desnutricao proteica, ferrica e de zinco, alem das vitaminicas. Apesar de raros, alguns quadros de desnutricao atingem tal gravidade que acaba sendo indicada internacao e, por vezes, procedimentos cirurgicos revisionais ou de reversao. Objetivo: : Apresentar proposta de cirurgia revisional para tratamento de desnutricao severa apos bypass gastrico. Metodos: : O procedimento consiste em reconstituir o transito alimentar pelo duodeno e jejuno proximal, mantendo o componente restritivo do bypass gastrico. Como estrategia adicional, e realizada resseccao do fundo gastrico, visando intensificar a supressao da grelina e evitando reganho excessivo de peso. Resultado: : Apos estabilizacao inicial com suporte hidroeletrlitico e nutricional, o procedimento foi realizado em dois pacientes como tratamento definitivo do quadro de desnutricao. Bons resultados foram observados em seguimento de um ano. Conclusao: : Como opcao de melhora e/ou resolucao da defasagem nutricional, a terapia cirurgica e uma das alternativas. Ainda nao ha consenso quanto a tecnica a ser utilizada. O procedimento aqui apresentado e baseado em fatores fisiopatologicos para o tratamento desta condicao, com bons resultados iniciais, sem efeitos colaterais significativos. Seguimento de mais longo prazo e necessario para determinacao de sua eficacia. PMID- 27683788 TI - THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I AND TYPE 2 DIABETES NOT CONTROLLED CLINICALLY. AB - Introduction: Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. Objective: : To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. Method: : Research was conducted in Pubmed, Medline, Pubmed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetes mellitus. In addition, representatives of the societies involved, as an expert panel, issued opinions. Results: : Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMI<35 kg/m2; Safety of metabolic surgery in patients with BMI<35 kg/m2; Long-term effects of surgery in patients with baseline BMI<35 kg/m2 and Proposal for a Metabolic Risk Score. Conclusion: : Metabolic surgery has well-defined mechanisms of action both in experimental and human studies. Gastrointestinal interventions in T2DM patients with IMC<=35 kg/m2 has similar safety and efficacy when compared to groups with greater BMIs, leading to the improvement of diabetes in a superior manner than clinical treatment and lifestyle changes, in part through weight loss independent mechanisms . There is no correlation between baseline BMI and weight loss in the long term with the success rate after any surgical treatment. Gastrointestinal surgery treatment may be an option for patients with T2DM without adequate clinical control, with a BMI between 30 and 35, after thorough evaluation following the parameters detailed in Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Introducao:: Mesmo considerando o avanco do tratamento clinico ocorrido nos ultimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda sao desanimadores quanto ao controle da obesidade e da diabete melito tipo 2 (DMT2),com grande parcela de doentes em tratamento clinico ficando fora da meta desejada de controle. Objetivo:: Apresentar proposta de Escore de Risco Metabolico para melhor orientar a indicacao cirurgica do diabete em pacientes com indice de massa corporea (IMC) mais baixo nos quais o uso de procedimento cirurgico para obesidade ainda e controverso. Metodo:: Foi realizada pesquisa nas bases de dados Pubmed, Medline, Pubmed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabolica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opinioes em pontos nos quais nao existia na literatura trabalhos com graus de evidencia elevados. Resultados:: Foram encontrados 45 artigos relacionados que foram analisados pelos criterios da medicina baseada em evidencias. As opinioes agrupadas procuraram responder as seguintes questoes: Porque cirurgia metabolica e nao bariatrica?; Mecanismos envolvidos no controle glicemico; IMC como criterio isolado de indicacao cirurgica para o DMT2 nao controlado; Resultados de estudos de cirurgia metabolica em IMC<35 kg/m2; Seguranca da cirurgia metabolica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabolico. Conclusao:: A cirurgia metabolica tem mecanismos de acao bem definidos tanto em estudos experimentais quanto em seres humanos. As intervencoes gastrointestinais em diabeticos com IMC<=35 kg/m2 possuem seguranca e eficacia semelhantes aos grupos com IMCs maiores, levando a melhora do diabete de forma superior aos tratamentos clinicos e mudancas de estilo de vida, em parte atraves de mecanismos independentes da perda ponderal. Nao ha correlacao entre o IMC inicial e perda ponderal em longo prazo com os indices de sucesso do tratamento cirurgico. O tratamento cirurgico e opcao para os pacientes portadores de DMT2 sem adequado controle clinico, com IMC entre 30 e 35, apos minuciosa avaliacao seguindo os parametros dispostos no Escore de Risco Metabolico aqui proposto. DGYR e a tecnica indicada para os pacientes selecionados no Escore, existindo a possibilidade de indicacao da gastrectomia vertical para os casos em que exista contraindicacao para ela. O paciente deve ser avaliado por equipe multiprofissional envolvida na indicacao, preparo e acompanhamento apos as operacoes e acompanhados com monitorizacao de complicacoes micro e macrovasculares. PMID- 27683791 TI - PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENTOF DUMPING SYNDROME AND ITS RELATION TO BARIATRIC SURGERY. AB - Introduction: The dumping syndrome is frequent in bariatric surgery. It is probably the most common syndrome following partial or complete gastrectomy. Its prevalence in partial gastrectomy can reach up to 50%, thus it can be a significant complication arising from some types of bariatric surgeries. Objective: : Critical analysis on dumping syndrome, its pathophysiology, diagnosis and treatment. Methods: : A literature review was performed using the key words: 'dumping syndrome', 'bariatric surgery' and 'rapid dumping syndrome'. Inclusion criteria were: books, original works, case reports and meta-analyzes, and the exclusion criterion was literature review. Concerning the publication time, articles were screened between 1960 and May 2015. Results: : The dumping syndrome is complication arising from obesity surgeries, but also can be a result of vagus nerve damage. Diagnosis is done primarily through the use of questionnaires based on scores. Conclusion: : The Sigstad score and Arts survey are valid means for assessing the dumping syndrome. Initial therapy consists in the adoption of dietary measures, short acting drugs administration. Introducao: : A sindrome de dumping e frequente apos operacoes bariatricas. E, provavelmente, a mais comum das sindromes que sucedem gastrectomias parciais ou completas. Sua prevalencia, em gastrectomias parciais pode chegar a ate 50%, tornando-se assim complicacao significante em alguns tipos de operacoes bariatricas. Objetivo: : Realizar analise critica sobre a sindrome de dumping em sua fisiopatologia, diagnostico e tratamento. Metodos: : Foi realizada revisao bibliografica utilizando os descritores: 'sindrome de dumping', 'cirurgia bariatrica' e 'sindrome do esvaziamento rapido'. Os criterios de inclusao foram: livros, trabalhos originais, relatos de caso e metanalises; excluiram-se as revisoes bibliograficas. Quanto ao tempo de publicacao, foram selecionados artigos entre 1960 e maio de 2015. Resultados: : A sindrome de dumping e complicacao gastrointestinal oriunda de operacoes para obesidade, mas tambem pode ocasionar se como consequencia de danos no nervo vago. Seu diagnostico e realizado primordialmente atraves da aplicacao de questionarios baseados em pontuacoes. Conclusao: : O escore de Sigstad e questionario de Arts sao meios validos para avaliacao da sindrome de dumping. A terapia inicial consiste na adocao de medidas dieteticas, ou farmacos administraveis de acao curta. PMID- 27683789 TI - TENDINOPATHY AND OBESITY. AB - Introduction: : Tendinopathies and tendon tears account for over 30% of all musculoskeletal consultations. Obesity, which is becoming one of the world's most prevalent public health issues, may be associated with this condition. Objective: : To review the literature about tendinopathies and obesity association. Methods: : This is a descriptive exploratory study using the portal Medline. Literature in English language from 2006 to 2014 were reviewed. Results: : The pathogenesis of tendinopathies includes inflammatory, regenerative and degenerative processes that happen simultaneously from early to late phases of the disease. Mechanical stress upon tendons seems to be one of the most important factors to initiate the inflammatory response, but it's not the only one that can deflagrate it: there are other extrinsic, genetic and metabolic factors that may be involved. Therefore, tendinopathies in obese patients can be due to tendon overload because of the excess of weight, but also because of increased production of pro inflammatory mediators related to fat tissue such as adipokines. This pro inflammatory state that obese people can suffer is known as adiposopathy, or sick fat syndrome. Weight loss is associated with decrease in adipokines and improvement of musculoskeletal symptoms. Conclusion: : The relation of obesity and tendinopathies is supported by evidences of recent studies, exemplified in this review of literature. Introducao: : As tendinopatias e as fissuras em tendoes respondem por 30% de todas as consultas medicas. A obesidade, que esta se tornando um dos problemas de saude publica mais prevalentes no mundo, pode estar associada com esta condicao. Objetivo: Revisar a literatura acerca da associacao entre obesidade e tendinopatias. Metodos: : Este e um estudo exploratorio e descritivo utilizando artigos em lingua inglesa do portal medico Medline, do periodo de 2006 a 2014. Resultados: : Na patogenese das tendinopatias incluem-se elementos inflamatorios, regenerativos e degenerativos que aparecem de maneira simultanea em todos os estagios da doenca. O estresse mecanico sobre os tendoes parece ser um dos mais importantes na promocao do processo inflamatorio inicial. Todavia nao e o unico. Existem fatores ambientais, geneticos e metabolicos atuando de maneira ativa. Portanto, as tendinopatias em individuos obesos podem se dever a sobrecarga mecanica pelo excesso de peso, mas, tambem, pelo aumento na producao de mediadores pro-inflamatorios relacionados ao tecido adiposo, como as adipocinas. O estado pro-inflamatorio existente no individuo obeso e conhecido como adiposopatia ou sindrome da "gordura doente". A perda de peso esta associada com decrescimo das adipocinas e diminuicao da sintomatologia musculoesqueletica. Conclusao: : A associacao da obesidade com tendinopatias tem sido fundamentada em estudos recentes como os desta revisao de literatura. PMID- 27683790 TI - THE ALCOHOL CONSUMPTION IS AMENDED AFTER BARIATRIC SURGERY? AN INTEGRATIVE REVIEW. AB - Background: Bariatric surgery has been an alternative when conservative methods of weight loss fail. Patients undergoing bariatric surgery have an increased risk of up to 6.5% of problems related to alcohol. Objective: : Integrative review out to analyze the change of alcohol consumption in this public. Method: : Database was accessed from June of 2015 to January of 2016 by searching "bariatric surgery" AND "alcoholism", and their Portuguese equivalents. ScienceDirect, PubMed, Lilacs and Medline, besides manual search, were searched. To be included, the paper should have been published between 2005-2016 and related to bariatric surgery and alcoholism. Theses, dissertations, unpublished papers, case reports and theoretical studies were excluded, and a database was subsequently composed. Results: : In 2005 there was only a review of change in alcohol metabolism in patients undergoing bariatric surgery. There were no publications in 2006. In 2007, only one study was published, and it did not meet the inclusion criteria. In 2010, there was an increase of 13% in publications and of 20% in 2012, reaching 40% in 2013. Conclusion: : The prevalence and incidence of alcohol consumption in relation to the postoperative time was six months to three years with higher incidence for follow-up treatment by men. Roux-en-Y gastric bypass showed greater association with increased consumption of alcohol during the postoperative period. Alcohol consumption proved to be essential to be faced in bariatric surgery. Introducao: A cirurgia bariatrica tem-se mostrado alternativa para o insucesso dos metodos conservadores de emagrecimento. Pacientes submetidos a ela tem 6,5% aumento do risco de terem problemas relacionados ao alcool. Objetivo: : Realizar revisao integrativa para verificar alteracao do consumo de alcool neste publico. Metodo: : A base de dados Science Direct, PubMed, Lilacs, Medline e busca manual foram acessadas entre os meses de junho de 2015 a janeiro de 2016 com os descritores "cirurgia bariatrica" e "alcoolismo" e equivalentes em ingles Os criterios de inclusao foram publicacoes entre junho de 2005 a janeiro de 2016 relacionadas a cirurgia bariatrica e ao consumo de alcool. Foram excluidas teses, dissertacoes, trabalhos nao publicados, relatos de casos e estudos teoricos. Resultados: : No ano de 2005 houve somente uma revisao relacionada a alteracao do metabolismo do alcool em pacientes submetidos a cirurgia bariatrica. Nao houve publicacoes em 2006. Em 2007, houve uma publicacao fora dos criterios desta revisao. Em 2010, observou-se aumento de 13% e 20% em 2012, atingindo 40% em 2013. Conclusao: : A prevalencia e a incidencia do consumo de alcool em relacao ao tempo de pos-operatorio foi de seis meses a tres anos com maior seguimento do tratamento por homens. O bypass gastrico em Y-de-Roux apresentou maior associacao com o aumento do consumo de alcool durante o pos operatorio. O consumo de alcool e problema que deve ser enfrentado na realizacao da cirurgia bariatrica. PMID- 27683792 TI - IMPACT OF VITAMIN D AND CALCIUM DEFICIENCY IN THE BONES OF PATIENTS UNDERGOING BARIATRIC SURGERY: A SYSTEMATIC REVIEW. AB - Introduction: : Bariatric surgery is considered the most effective tool in the control and treatment of severe obesity, but patients undergoing this procedure are at increased risk of developing nutritional deficiencies by limiting the intake and absorption of many nutrients. Objective: : To assess the impact of vitamin D deficiency and calcium in bone in patients after gastric bypass in Roux en-Y, pointing directly at the type of administration, doses and effects after surgery. Method: : Was conducted a systematic review with articles related to the topic of the last 10 years searched in PubMed (US National Library of Medicine National Institutes of Health, Medline, Lilacs, Scielo and Cochrane using the headings "bariatric surgery", "bone", "obesity", "vitamin D '', "calcium" AND "absorption". Exclusion criteria to research on animals, smokers, pregnant women and patient treated with bisphosphonates. Results: : Five articles were included in this review. All refer that bariatric surgery can lead to nutritional deficiencies and poor absorption of fats and fat-soluble vitamins and other micronutrients such as calcium. Conclusion: : Patients submitted to RYGB should make use of multivitamins and minerals especially vitamin D and calcium to prevent bone fractures. Monitoring, treatment and control of risk factors are essential to prevent complications after this operation. Introducao: : A cirurgia bariatrica e considerada o tratamento mais eficaz no controle e tratamento da obesidade severa; porem, individuos submetidos a este procedimento apresentam maior risco de desenvolver deficiencias nutricionais pela limitacao na ingestao e absorcao de muitos nutrientes. Objetivo: : Avaliar o impacto da deficiencia de vitamina D e do calcio osseo de pacientes apos gastroplastia em Y-de-Roux, relacionando tipo de administracao, dose e efeito pos-cirurgico. Metodo: : Realizou-se revisao sistematica com artigos relacionados ao tema dos ultimos 10 anos e pesquisados na PubMed (US National Library of Medicine National Institutes of Health, Medline, Lilacs, Scielo e Cochrane usando os descritores "bariatric surgery", "bone", "obesity", " vitamin D'', "calcium'' AND "absortion". Foram excluidos os estudos em animais, fumantes, gravidas ou gestantes e individuos que ingeriram bisfosfonatos. Resultados: : Foram incluidos ao final cinco artigos. Todos referem que a cirurgia bariatrica pode levar a deficiencias nutricionais como ma absorcao de gorduras, vitaminas lipossoluveis, micronutrientes e calcio. Conclusao: : Os pacientes submetidos ao RYGB devem fazer uso de polivitaminicos e minerais principalmente a vitamina D e o calcio para evitar fraturas osseas. Monitoramento, tratamento e controle dos fatores de risco sao essenciais para prevenir estas complicacoes apos a operacao. PMID- 27683793 TI - SLEEVE GASTRECTOMY IN PATIENTS WITH MORBID OBESITY AND HIV. AB - Introduction:: It is estimated that there are nearly 40 million people with the human immunodeficiency virus (HIV) worldwide. Due to the advent of antiretroviral drugs, it has been observed increasing in obesity and metabolic rates among patients undergoing treatment. Thus, numerous surgical therapies for weight loss are proposed for continuous improvement in health of patients with HIV, being the vertical gastrectomy an option for intact intestinal transit. Objective:: To evaluate the applicability of the vertical gastrectomy in patients with morbid obesity and HIV. Methods:: Was conducted a systematic review of the literature, in the electronic databases Scopus, Pubmed, Cinahl, Scielo, Cochrane and Lilacs, from 1998 to 2015. MeSH headings used in data collection were "Gastrectomy" and "Morbid obesity" being combined with the descriptor "HIV". Were found 2148 articles in Scopus, 1234 in PubMed and 784 in Cinahl. The articles were analyzed by the Jadad Quality Scale, being reduced to 40 articles, subsequently reassessed using an elaborated form by the Critical Appraisal Skills Programme (CASP), reaching 12 articles in the end. Conclusion:: It was found that vertical gastrectomy constitutes a safe and effective method, with low mortality and low rate of postoperative complications, being recommended as surgical technique in patients with obesity, HIV and comorbidities. Introducao:: Estima-se que haja quase 40 milhoes de pessoas com o virus da imunodeficiencia adquirida (HIV) no mundo. Com o advento dos antirretrovirais, observou-se aumento da obesidade e de taxas metabolicas nos pacientes em tratamento. Assim, inumeras terapias cirurgicas para a perda de peso estao sendo estudadas para a melhoria continua da saude dos pacientes com HIV, sendo a gastrectomia vertical uma opcao de transito integro. Objetivo:: Avaliar a aplicabilidade da gastrectomia vertical em pacientes com obesidade morbida e HIV. Metodos:: Foi realizada revisao sistematica de literatura, de artigos publicados nas bases eletronicas de dados Scopus, Pubmed, Cinahl, Scielo, Cochrane e Lilacs, no periodo de 1998 a 2015. Os descritores do MeSH utilizados na coleta dos dados foram "Gastrectomia" e "Obesidade morbida", sendo combinados com o descritor "HIV". Resultados: : Foram encontrados 2.148 artigos na Scopus, 1.234 no Pubmed e 784 na Cinahl. Os artigos foram analisados pela Escala de Qualidade de Jadad, reduzindo para um total de 40 artigos, os quais foram posteriormente reavaliados, utilizando um formulario elaborado pelo Critical Appraisal Skills Programme (CASP), chegando ao montante de 12 artigos ao final. Conclusao:: Verificou-se que a gastrectomia vertical constitui metodo seguro e eficaz, apresentando baixa morbimortalidade e baixo indice de complicacoes pos-operatorias, sendo tecnica cirurgica segura para uso em pacientes com obesidade, HIV e comorbidades. PMID- 27683795 TI - Misadventure during laparoscopic sleeve gastrectomy: why it happened? how to prevent and recover from it? PMID- 27683794 TI - FROM COMPLEX EVOLVING TO SIMPLE: CURRENT REVISIONAL AND ENDOSCOPIC PROCEDURES FOLLOWING BARIATRIC SURGERY. AB - Background: Roux-en-Y gastric bypass (RYGB) is a standard therapy in bariatric surgery. Sleeve gastrectomy and gastric banding, although with good results in the literature, are showing higher rates of treatment failure to reduce obesity associated morbidity and body weight. Other problems after bariatric may occur, as band erosion, gastroesophageal reflux disease and might be refractory to medication. Therefore, a laparoscopic conversion to a RYGB can be an effective alternative, as long as specific indications for revision are fulfilled. Objective: The objective of this study was to analyse own and literature data on revisional bariatric procedures to evaluate best alternatives to current practice. Methods: Institutional experience and systematic review from the literature on revisional bariatric surgery. Results: Endoscopic procedures are recently applied to ameliorate failure and complications of bariatric procedures. Therapy failure following RYGB occurs in up to 20%. Transoral outlet reduction is currently an alternative method to reduce the gastrojejunal anastomosis. The diameter and volume of sleeve gastrectomy can enlarge as well, which can be reduced by endoscopic full-thickness sutures longitudinally. Dumping syndrome and severe hypoglycemic episodes (neuroglycopenia) can be present in patients following RYGB. The hypoglycemic episodes have to be evaluated and usually can be treated conventionally. To avoid partial pancreatectomy or conversion to normal anatomy, a new laparoscopic approach with remnant gastric resection and jejunal interposition can be applied in non-responders alternatively. Hypoglycemic episodes are ameliorated while weight loss is sustained. Conclusion: Revisional and endoscopic procedures following bariatric surgery in patients with collateral symptomatic or treatment failure can be applied. Conventional non-surgical approaches should have been applied intensively before a revisional surgery will be indicated. Former complex surgical revisional procedures are evolving to less complicated endoscopic solutions. PMID- 27683796 TI - Laparoscopic re-sleeve gastrectomy for weight regain after modified laparoscopic sleeve gastrectomy: first case report and surgery in South America. PMID- 27683797 TI - GASTRIC RESERVOIR NECROSIS POST GASTRO-JEJUNAL BYPASS. THE IMPORTANCE OF CLINICAL EVALUATION IN THE DECISION MAKING PROGRESS: CASE REPORT. PMID- 27683798 TI - Long-term Efficacy of Vedolizumab for Crohn's Disease. AB - Background and Aims: Vedolizumab is a gut-selective alpha4beta7 integrin antagonist therapy for ulcerative colitis and Crohn's disease. The GEMINI long term safety [LTS] trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn's disease. Methods: Patients from the C13004, GEMINI 2 and GEMINI 3 studies and vedolizumab-naive patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks. Data were collected from May 22, 2009 to June 27, 2013. Outcomes of clinical response and remission, defined by the Harvey-Bradshaw Index, and health-related quality of life [HRQL] were assessed for up to 152 weeks of treatment in the efficacy population. Results: Among patients with response at week 6 in GEMINI 2 who received vedolizumab continuously, 83% [n=100/120] and 89% [n=62/70] of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks [GEMINI 2] to every 4 weeks [GEMINI LTS] improved outcomes in patients who had withdrawn early from GEMINI 2, with 47% [n=27/57] experiencing clinical response and 32% [n=18/57] in remission at week 52 of GEMINI LTS [up from 39% and 4% before the dose increase]. Similar improvements were observed regardless of prior tumour necrosis factor [TNF] antagonist exposure. Long-term benefits of HRQL were also observed. Conclusions: The clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. Increased dosing frequency might improve outcomes in patients who lose response to conventional 8-weekly dosing. PMID- 27683799 TI - Development and Validation of Risk Matrices for Crohn's Disease Outcomes in Patients Who Underwent Early Therapeutic Interventions. AB - Introduction: The establishment of prognostic models for Crohn's disease [CD] is highly desirable, as they have the potential to guide physicians in the decision making process concerning therapeutic choices, thus improving patients' health and quality of life. Our aim was to derive models for disabling CD and reoperation based solely on clinical/demographic data. Methods: A multicentric and retrospectively enrolled cohort of CD patients, subject to early surgery or immunosuppression, was analysed in order to build Bayesian network models and risk matrices. The final results were validated internally and with a multicentric and prospectively enrolled cohort. Results: The derivation cohort included a total of 489 CD patients [64% with disabling disease and 18% who needed reoperation], while the validation cohort included 129 CD patients with similar outcome proportions. The Bayesian models achieved an area under the curve of 78% for disabling disease and 86% for reoperation. Age at diagnosis, perianal disease, disease aggressiveness and early therapeutic decisions were found to be significant factors, and were used to construct user-friendly matrices depicting the probability of each outcome in patients with various combinations of these factors. The matrices exhibit good performance for the most important criteria: disabling disease positive post-test odds = 8.00 [2.72-23.44] and reoperation negative post-test odds = 0.02 [0.00-0.11]. Conclusions: Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management. PMID- 27683800 TI - Long-term Efficacy of Vedolizumab for Ulcerative Colitis. AB - Background and Aims: The GEMINI long-term safety [LTS] study is a continuing phase 3 trial investigating the safety and efficacy of vedolizumab, an alpha4beta7 integrin antagonist for ulcerative colitis [UC] and Crohn's disease. We provide an interim analysis of efficacy in patients with UC. Methods: Patients from the C13004 and GEMINI 1 studies and a cohort of vedolizumab-naive patients received open-label vedolizumab every 4 weeks. Interim data were collected from May 22, 2009 to June 27, 2013. Clinical response and remission, evaluated using partial Mayo scores, and health-related quality of life [HRQL] were assessed for up to 152 weeks of cumulative treatment in the efficacy population. Results: As of June 27, 2013, 63% of the efficacy population [n = 532/845] were continuing treatment. Among patients who responded to vedolizumab induction and had data available, 88% [n = 120/136] were in remission after 104 weeks of exposure (96% [n = 70/73] after 152 weeks). Among patients who withdrew from every-8-week vedolizumab maintenance in GEMINI 1 [n = 32] before week 52, increased dosing to every 4 weeks in GEMINI LTS resulted in response and remission rates of 41% and 28%, respectively, after 52 weeks, an increase from 19% and 6%, respectively, from before the dose increase. Similar benefits were demonstrated regardless of prior tumour necrosis factor-antagonist exposure. Durable benefits on HRQL were also observed. Conclusions: Patients with UC experienced clinical and HRQL improvements with continued vedolizumab treatment. Increased dosing frequency to every 4 weeks was beneficial in patients who had loss of response to 8-weekly dosing. PMID- 27683801 TI - Cell-specific Activation of the Nrf2 Antioxidant Pathway Increases Mucosal Inflammation in Acute but Not in Chronic Colitis. AB - Background and Aims: The transcription factor Nrf2 is a major modulator of the cellular antioxidant response. Oxidative burst of infiltrating macrophages leads to a massive production of reactive oxygen species in inflamed tissue of inflammatory bowel disease patients. This oxidative burst contributes to tissue destruction and epithelial permeability, but it is also an essential part of the antibacterial defence. We therefore investigated the impact of the Nrf2 orchestrated antioxidant response in both acute and chronic intestinal inflammation. Methods: To study the role of Nrf2 overexpression in mucosal inflammation, we used transgenic mice conditionally expressing a constitutively active form of Nrf2 [caNrf2] either in epithelial cells or in the myeloid cell lineage. Acute colitis was induced by dextran sulphate sodium [DSS] in transgenic and control animals, and changes in gene expression were evaluated by genome-wide expression studies. Long-term effects of Nrf2 activation were studied in mice with an IL-10-/- background. Results: Expression of caNrf2 either in epithelial cells or myeloid cells resulted in aggravation of DSS-induced acute colitis. Aggravation of inflammation by caNrf2 was not observed in the IL-10-/- model of spontaneous chronic colitis, where even a trend towards reduced prolapse rate was observed. Conclusions: Our findings show that a well-balanced redox homeostasis is as important in epithelial cells as in myeloid cells during induction of colitis. Aggravation of acute DSS colitis in response to constitutive Nrf2 expression emphasises the importance of tight regulation of Nrf2 during the onset of intestinal inflammation. PMID- 27683802 TI - Ano-genital Granulomatosis and Crohn's Disease: A Case Series of Males Presenting with Genital Lymphoedema. AB - Background and Aims: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease and optimal methods of treatment are poorly understood. Methods: A retrospective casenote review of 25 male patients with ano-genital granulomatosis presenting with genital lymphoedema was performed to determine the clinical and histopathological features of this condition and its relationship to intestinal Crohn's disease. Results: A combination of penile and scrotal oedema was reported at presentation in 80% of patients; 40% of patients had associated intestinal Crohn's disease. The average time from symptom onset to diagnosis was 52.7 months. Half of cutaneous biopsies contained non-caseating granulomas and 14% contained intralymphatic granulomas. In all, 72% of patients responded to oral steroids initially but recurrence was common. Complete or partial response was achieved in 60% of patients treated with azathioprine. Three of six patients responded to anti-tumour necrosis factor [TNF] therapy. A small proportion of patients required circumcision or de-bulking surgery for more debilitating disease. Conclusions: Ano-genital granulomatosis is a rare condition that presents with genital lymphoedema, and there is frequently a protracted delay in diagnosis. There is a very strong association with intestinal Crohn's disease. Genital lymphoedema associated with gastrointestinal symptoms should prompt careful evaluation to exclude both ano-genital granulomatosis and Crohn's disease. PMID- 27683803 TI - African Americans and Short-Term Outcomes after Surgery for Crohn's Disease: An ACS-NSQIP Analysis. AB - Background: Previous reports on racial disparities in the treatment of Crohn's disease [CD] in African American [AA] patients have shown differences in both medical and surgical treatments in this population. No study thus far has examined the effect of AA race on outcomes after surgery for CD. Methods: Utilizing the National Surgical Quality Improvement Program [NSQIP] Participant User File [PUF] for the years 2005-2013, we examined the effect of AA race on postoperative complications in patients with CD undergoing intestinal surgery. Results: AA patients had a significantly higher rate of complications overall compared to non-AA patients [23.5% vs 18.9%, p = 0.002]. Postoperative sepsis [10.9% vs 6.6%, p < 0.001] and surgical site infection [17.6% vs 14.8%, p = 0.037] were most significant. After adjustment for age, sex, preoperative disease severity and lifestyle factors [smoking], race remained a statistically significant factor in postoperative complication rate. Only after additional adjustment was made for comorbidities and American Society of Anesthesiologists class did race lose significance within our model. Conclusion: African Americans experience a greater amount of postoperative complications following surgery for Crohn's disease. Preoperative disease management, addressing smoking status and control of comorbid disease are important factors in addressing the racial disparities in the surgical treatment of Crohn's disease. PMID- 27683804 TI - Storage of Calophyllum brasiliense Cambess. seeds. AB - Calophyllum brasiliense is a species native to Brazil and has potential for use in the timber industry, in the reforestation of degraded areas, besides having medicinal properties. Its propagation is mainly by seeds which, depending on their recalcitrant characteristics, leads to difficulty in conservation, due to changes in its physiological potential during storage. Aiming to contribute to the expansion of its cultivation, rational use and conservation, the objective of this study was to investigate the behavior of C. brasiliense seeds during storage. Different packings (paper, aluminum and polyethylene) and environmental conditions (room temperature and cold chamber) were quarterly tested over 12 months, by evaluating germination viability and vigor. Based on the results, it was concluded that packaging in polyethylene and freezer storage provided the best conditions for the conservation of seeds, keeping them viable for a period of nine months. PMID- 27683805 TI - Seasonal variation of limnological features and trophic state index of two oligotrophic reservoirs of southeast Brazil. AB - Limnological features of two reservoirs were studied in dry (August 2013) and rainy (January 2014) periods to evaluate the water quality that supply the city of Guarulhos, southeast Brazil. Water samples were collected in three depths and the following characteristics were measured: alkalinity, dissolved O2, free and total CO2, HCO3, soluble reactive silica, dissolved and total nitrogen and phosphorus, and chlorophyll-a. Water transparency was also measured and temperature, pH and electric conductivity profiles were obtained. Great seasonal and low spatial variability of the water characteristics occurred in the reservoirs. High values of water transparency, free CO2 availability, and low of pH, soluble reactive silica and total and dissolved nutrients values were recorded at the dry period, and different conditions were found at the rainy season. The two reservoirs were characterized by low nutrients, chlorophyll-a and turbidity, and high transparency, these features being typical of oligotrophic systems. The two reservoirs still remain under low anthropogenic impact conditions, and are presently considered reference systems for the SPMR, Sao Paulo Metropolitan Region. The need for actions that will reduce the input of nutrients from the neighboring cities and the main tributaries of the hydrographic basin is emphasized to maintain the ecological quality of the reservoirs and their reference conditions among the SPRM reservoirs. PMID- 27683806 TI - Thermal and photo-stability of the antioxidant potential of Spirulina platensis powder. AB - This work aimed to evaluate the thermal and photo stability of the antioxidant potential (AP) of the Spirulina platensis biomass. Thermal stability was established at 25oC, 40oC and 50oC for 60 days, in the dark, protected from light. Photo stability was evaluated using UV (15 W, lambda = 265 nm) and fluorescent (20 W, 0.16 A, power factor FP > 0.5, 50/60 Hz, 60 lm/w, 1200 lm) light for 90 days in capsules, glass and Petri dishes, at room temperature. The AP of the biomass in these conditions was determined at intervals (every 7 and 30 days in the studies of thermal and photo stability, respectively) using the induction of the oxidation of a lipid system by heat and aeration. In this lipid system, the biomass submitted to degradation was used as an antioxidant. The kinetics of the reaction was determined by the Arrhenius method. Thermal degradation was found to follow zero order kinetics, whereas photo degradation followed first order kinetics. The AP decreased 50% after 50 days at 25 degrees C. At 40 degrees C and 50 degrees C, the AP decreased more than 50% after 35 and 21 days of exposition, respectively. The decrease of the AP of Spirulina was more sensible to UV and fluorescence light. After 30 days of exposition, the AP decreased more than 50% in all storage conditions tested. The antioxidant potential of Spirulina platensis is easily degraded when the biomass is exposed to heat and light, indicating the need for care to be taken in its storage. PMID- 27683807 TI - Host-parasite relationship between Biomphalaria amazonica (Paraense, 1966) and Schistosoma mansoni (Sambon, 1907). AB - Biomphalaria amazonica is a planorbid species considered a potential host of Schistosoma mansoni. It is widely distributed in the Neotropical zone, particularly in the North and Centre-West of Brazil and in the North of Bolivia. The aim of the present study was to determine the host-parasite relationship between B. amazonica and S. mansoni (BH and SJ strains). Specimens of B. amazonica and their snail-conditioned water were examined in terms of their ability to attract miracidia. The infectivity of the mollusks was determined by exposing them to 20 miracidia of both strains. Sporocyst development and amebocyte reactions were studied after each mollusk specimen was exposed to 100 miracidia. Although no cercariae were eliminated, specimens of B. amazonica proved capable of attracting 77% of the miracidia they were exposed to. Viable sporocysts with no amebocyte reaction were found 96 hours after the exposure to miracidia. These results indicate the susceptibility of B. amazonica to the BH and SJ strains of S. mansoni, and therefore demonstrate the importance of this planorbid species as a potential vector of the trematode in the areas where it occurs. PMID- 27683808 TI - The efficacy of clove oil as an anaesthetic and in euthanasia procedure for small sized tropical fishes. AB - Clove oil is used as a fish anesthetic because it is a natural and inexpensive product with low toxicity risks. The goal of the present study was to determine the appropriate concentration of clove oil for small-sized tropical fish to be used in mark-recapture studies or when individuals are to be sacrificed. We applied three different clove oil concentrations (D1=0.05 mL, D2=0.10 mL and D3=0.20 mL per 500 mL of water) on three small-sized fish species. We found a negative relationship between induction time and treatment for two species (Hyphessobrycon sp.1 and Hemigrammus sp.), while concentration was unrelated to recovery time. Fish body length was positively related to induction time in the D2 treatment for Hemigrammus sp., and negatively for Hyphessobrycon sp.1 in the D1 treatment, but was unrelated to recovery time for three species and treatments. Mortality rates varied across treatments, but higher rates were observed with higher clove oil concentrations. We conclude that 0.05 mL of clove oil per 500 mL of water is the most efficient dose for studies where fish will be released back to their natural habitats, while 0.20 mL of clove oil is recommended for studies that require fish euthanization for further laboratory analyses. PMID- 27683809 TI - Susceptibility of Biomphalaria glabrata submitted to concomitant infection with Angiostrongylus costaricensis and Schistosoma mansoni. AB - The easy adaptation of Angiostrongylus costaricensis, nematode responsible for abdominal angiostrongyliasis to several species of terrestrial and freshwater molluscs and the differences observed in the interactions of trematodes with their intermediate hosts have induced us to study the concomitant infection of Biomphalaria glabrata with Schistosoma mansoni and A. costaricensis. Prior exposure of B. glabrata to A. costaricensis (with an interval of 48 hours), favored the development of S. mansoni, observing higher infection rate, increased release of cercariae and increased survival of molluscs, when compared to molluscs exposed only to S. mansoni. Prior exposure of B. glabrata to A. costaricensis and then to S. mansoni also enabled the development of A. costaricensis since in the ninth week of infection, higher amount of A. costaricensis L3 larvae was recovered (12 larvae / mollusc) while for molluscs exposed only to A. costaricensis, the number of larvae recovered was lower (8 larvae / mollusc). However, pre-exposure of B. glabrata to S. mansoni (with an interval of 24 hours), and subsequently exposure to A. costaricensis proved to be very harmful to B. glabrata, causing extensive mortality of molluscs, reduced pre patent period to release cercariae and greater recovery of L3 A. costaricensis larvae. PMID- 27683810 TI - Distribution and genetic diversity of the human polyomaviruses JC and BK in surface water and sewage treatment plant during 2009 in Porto Alegre, Southern Brazil. AB - The human polyomaviruses JC and BK (JCPyV and BKPyV) are ubiquitous, species specific viruses that belong to the family Polyomaviridae. These viruses are known to be excreted in human urine, and they are potential indicators of human wastewater contamination. In order to assess the distribution of both JCPyV and BKPyV in urban water samples collected from a sewage treatment plant (STP) and from a canalized water stream of Porto Alegre, Brazil, two nested-PCR assays were optimized and applied to the samples collected. The amplicons obtained were submitted to sequencing, and the sequences were analyzed with sequences of human polyomaviruses previously deposited in GenBank. Twelve out of 30 water samples (40%) were JCPyV positive, whereas six samples (20%) were BKPyV positive. The sequencing results confirmed the presence of JCPyV subtypes 1 and 3, whereas only BKPyV Ia and Ib were found. This study shows for the first time the presence of human polyomaviruses in surface water and in samples collected in a sewage treatment plant in southern Brazil. PMID- 27683811 TI - Assessment of the impact of changes in temperature in Biomphalaria glabrata (Say, 1818) melanic and albino variants infected with Schistosoma mansoni (Sambon, 1907). AB - Fluctuations in population density of planorbid hosts of S. mansoni are influenced by climatic factors. The knowledge about interference from changes in water temperature in these populations is an important aspect of the epidemiology of schistosomiasis. In this experiment, it is explored the influence of different temperatures on the development of Schistosoma mansoni in Biomphalaria glabrata melanic and albino variants. The results indicated an intrinsic relationship between temperature and development of the parasite in the intramollusc phase, independent of the pigmentation of the mantle of the molluscs. The higher the temperature, the shorter the period necessary for the development of the parasite was while the higher the mortality of infected mollusks. It is concluded that, in the presence of climate change, the increasement of temperature in cold and flooded regions may encourage the establishment of new foci of transmission of schistosomiasis by changing the geographic extent and extending the epidemiological transmission potential. In warm climates, higher temperatures, however, could compromise the transmission of the disease because of biological stress suffered by parasite and host. Under these conditions, it can result in the death of the parasite or a change in their ability to infect new host species of molluscs in new areas. Mantle pigmentation patterns in molluscs have not shown significant interference in the development of the parasite. PMID- 27683812 TI - High species richness of native pollinators in Brazilian tomato crops. AB - Pollinators provide an essential service to natural ecosystems and agriculture. In tomatoes flowers, anthers are poricidal, pollen may drop from their pore when flowers are shaken by the wind. However, bees that vibrate these anthers increase pollen load on the stigma and in fruit production. The present study aimed to identify the pollinator richness of tomato flowers and investigate their morphological and functional traits related to the plant-pollinator interaction in plantations of Central Brazil. The time of anthesis, flower duration, and the number and viability of pollen grains and ovules were recorded. Floral visitors were observed and collected. Flower buds opened around 6h30 and closed around 18h00. They reopened on the following day at the same time in the morning, lasting on average 48 hours. The highest pollen availability occurred during the first hours of anthesis. Afterwards, the number of pollen grains declined, especially between 10h00 to 12h00, which is consistent with the pollinator visitation pattern. Forty bee species were found in the tomato fields, 30 of which were considered pollinators. We found that during the flowering period, plants offered an enormous amount of pollen to their visitors. These may explain the high richness and amount of bees that visit the tomato flowers in the study areas. The period of pollen availability and depletion throughout the day overlapped with the bees foraging period, suggesting that bees are highly effective in removing pollen grains from anthers. Many of these grains probably land on the stigma of the same flower, leading to self-pollination and subsequent fruit development. Native bees (Exomalopsis spp.) are effective pollinators of tomato flowers and are likely to contribute to increasing crop productivity. On the other hand, here tomato flowers offer large amounts of pollen resource to a high richness and amount of bees, showing a strong plant-pollinator interaction in the study agroecosystem. PMID- 27683813 TI - Nematodes associated with Iguana iguana (Linnaeus, 1758) (Squamata, Iguanidae) in Semi-arid areas of Northeastern Brazil. AB - Nematodes were analyzed in Iguana iguana, a large lizard Iguanidae that is widely distributed throughout the Americas. The aims of the study were investigate the helminths associated with the lizard, I. iguana in semi-arid areas of northeastern Brazil and analyze the parasitological indices (prevalence, and mean intensity of infection). A total of 18 specimens of I. iguana were examined (8 males and 10 females). The overall prevalence of infection was 66.6% (12/18), while in males, it was 75% (6/8) and in females, 60% (6/10). Iguana iguana was identified as a new host for Physaloptera sp., Atractis sp., Piratuba sp. and Subulura sp. This registered contributes to the knowledge of helminth diversity associated with this host. PMID- 27683814 TI - The impact of edge effect on termite community (Blattodea: Isoptera) in fragments of Brazilian Atlantic Rainforest. AB - Habitat fragmentation is considered to be one of the biggest threats to tropical ecosystem functioning. In this region, termites perform an important ecological role as decomposers and ecosystem engineers. In the present study, we tested whether termite community is negatively affected by edge effects on three fragments of Brazilian Atlantic Rainforest. Termite abundance and vegetation structure were sampled in 10 transects (15 * 2 m), while termite richness, activity, and soil litter biomass were measured in 16 quadrants (5 * 2 m) at forest edge and interior of each fragment. Habitat structure (i.e. number of tree, diameter at breast height and soil litter biomass) did not differ between forest edge and interior of fragments. Termite richness, abundance and activity were not affected by edge effect. However, differences were observed in the beta diversity between forest edge and interior as well as in the fragments sampled. The beta diversity partitioning indicates that species turnover is the determinant process of termite community composition under edge effect. Our results suggest that conservation strategies should be based on the selection of several distinct sites instead of few rich sites (e.g. nesting). PMID- 27683815 TI - First record of Scobina poeciloides (Ashmead, 1895) (Hymenoptera: Argidae) for Brazil and update of geographical distribution of three species of Scobina Lepeletier & Serville, 1828 for the State of Rio Grande do Sul. AB - It is recorded for the first time in the state of Rio Grande do Sul the occurrence of Scobina melanocephala (Lepeletier, 1823), Scobina thoracica (Jorgensen, 1913) and Scobina poeciloides (Ashmead, 1895), being this last the first record for Brazil. Scobina melanopyga (Klug, 1834) and Scobina torquata (Konow, 1903) were also found in the study. The analyzed material was collected utilizing Malaise traps in tobacco (Nicotiana tabacum L.) fields and is deposited at the Entomological Collection of Santa Cruz do Sul. PMID- 27683816 TI - Phosphoglycerate Kinase-A Novel Streptococcal Factor Involved in Neutrophil Activation and Degranulation. AB - BACKGROUND: Neutrophils have been proposed as important contributors to the hyperinflammatory responses that are associated with severe invasive Streptococcus pyogenes infections. In particular, streptococcal surface proteins have been implicated as potent neutrophil activators. Here we explore the impact of streptococcus-secreted factors on neutrophil activation and degranulation. METHODS: Primary human neutrophils were exposed to supernatants prepared from cultures of invasive S. pyogenes strains of varying serotypes in the stationary growth phase. Neutrophil activation was assessed by measurement of secreted resistin, an azurophilic granule marker, and by determination of the secretome profile, using mass spectrometry. RESULTS: Marked variation in resistin release and the neutrophil secretome profile were observed following exposure to different strains. A high resistin response was triggered exclusively by SpeB negative strains, suggesting that at least 1 stimulatory factor is susceptible to SpeB proteolytic degradation. Further analysis, including proteomics and stimulation analyses, identified phosphoglycerate kinase as a stimulatory factor for neutrophils. CONCLUSIONS: Taken together, results of this study reveal a novel secreted streptococcal factor that, in the absence of SpeB, can trigger neutrophil activation and degranulation. This finding is of interest in light of reports of hypervirulent SpeB-negative S. pyogenes variants present during invasive infections. PMID- 27683818 TI - Adeno-Associated Virus Serotype 9-Expressed ZMapp in Mice Confers Protection Against Systemic and Airway-Acquired Ebola Virus Infection. AB - Adeno-associated viral vectors can be used as a platform for delivering biological countermeasures against pandemic and biological threats. We show that vector delivery of two antibody components of the ZMapp product is effective in mice against systemic and airway challenge with a mouse-adapted strain of Ebola virus. This platform provides a generic manufacturing solution and overcomes some of the delivery challenges associated with repeated administration of the protective protein. PMID- 27683817 TI - CD36 Provides Host Protection Against Klebsiella pneumoniae Intrapulmonary Infection by Enhancing Lipopolysaccharide Responsiveness and Macrophage Phagocytosis. AB - Klebsiella pneumoniae remains an important cause of intrapulmonary infection and invasive disease worldwide. K. pneumoniae can evade serum killing and phagocytosis primarily through the expression of a polysaccharide capsule, but its pathogenicity is also influenced by host factors. We examined whether CD36, a scavenger receptor that recognizes pathogen and modified self ligands, is a host determinant of K. pneumoniae pathogenicity. Despite differences in serum sensitivity and virulence of 3 distinct K. pneumoniae (hypermucoviscous K1, research K2, and carbapenemase-producing ST258) strains, the absence of CD36 significantly increased host susceptibility to acute intrapulmonary infection by K. pneumoniae, regardless of strain. We demonstrate that CD36 enhances LPS responsiveness to K. pneumoniae to increase downstream cytokine production and macrophage phagocytosis that is independent of polysaccharide capsular antigen. Our study provides new insights into host determinants of K. pneumoniae pathogenicity and raises the possibility that functional mutations in CD36 may predispose individuals to K. pneumoniae syndromes. PMID- 27683820 TI - Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study. AB - We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had >=1 CSF HIV RNA load of >20 copies/mL (23% had >=1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips. PMID- 27683821 TI - Direct-Acting Antiviral-Induced Hepatitis C Virus Clearance Does Not Completely Restore the Altered Cytokine and Chemokine Milieu in Patients With Chronic Hepatitis C. AB - BACKGROUND: Persistent infection with hepatitis C virus (HCV) causes profound alterations of the cytokine and chemokine milieu in peripheral blood. However, it is unknown to what extend these alterations affect the progression of liver disease and whether HCV clearance normalizes soluble inflammatory mediators. METHODS: We performed multianalyte profiling of 50 plasma proteins in 28 patients with persistent HCV infection and advanced stages of liver fibrosis or cirrhosis and 20 controls with fatty liver disease. The patients were treated for 24 weeks with sofosbuvir and ribavirin and underwent sampling longitudinally. Ten patients experienced viral relapse after treatment cessation. RESULTS: The cytokine and chemokine expression pattern was markedly altered in patients with chronic HCV infection as compared to healthy controls and patients with nonalcoholic steatohepatitis. Distinct soluble factors were associated with the level of fibrosis/cirrhosis, viral replication, or treatment outcome. The baseline expression level of 10 cytokines distinguished patients with a sustained viral response from those who experienced viral relapse. While the majority of upregulated analytes declined during and after successful therapy, HCV clearance did not lead to a restoration of parameters that were suppressed. CONCLUSIONS: Chronic HCV infection appears to disrupt the milieu of soluble inflammatory mediators even after viral clearance. Thus, HCV cure does not lead to complete immunological restitution. PMID- 27683819 TI - MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor kappaB Activation and p53-Mediated Apoptotic Signaling. AB - BACKGROUND: This study examined the effect of microRNA-125b (miR-125b) on sepsis induced cardiac dysfunction. METHODS: Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) 7 days before cecal ligation and puncture (CLP)-induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n = 6/group). Survival was monitored following CLP induced sepsis (n = 12/group). RESULTS: LmiR-125b transfection significantly attenuated cardiac dysfunction due to CLP-induced sepsis. Fractional shortening and ejection fraction values were significantly (P < .05) higher in the LmiR-125b treated CLP group than in the untreated CLP group. Survival outcome in LmiR-125b transfected septic mice was markedly improved, compared with mice with CLP induced sepsis. Transfection of LmiR-125b into the heart significantly suppressed the expression of ICAM-1 and VCAM-1, decreased the accumulation of macrophages and neutrophils in the myocardium, and decreased serum levels of tumor necrosis factor alpha and interleukin 1beta by targeting tumor necrosis factor receptor associated factor 6 (TRAF6)-mediated nuclear factor kappaB (NF-kappaB) activation. In addition, sepsis-induced myocardial apoptosis was markedly attenuated by LmiR-125b transfection through suppression of p53, Bax, and Bak1 expression. In vitro transfection of endothelial cells with miR-125b mimics attenuate LPS-induced ICAM-1 and VCAM-1 expression by suppressing TRAF6 and NF kappaB activation. CONCLUSIONS: Increased myocardial miR-125b expression attenuates sepsis-induced cardiac dysfunction and improves survival. miR-125b may be a target for septic cardiomyopathy. PMID- 27683824 TI - NICE clinical guideline NG39: Major trauma: assessment and initial management. PMID- 27683823 TI - Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China. AB - Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose >=30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI. PMID- 27683825 TI - COA7 (C1orf163/RESA1) mutations associated with mitochondrial leukoencephalopathy and cytochrome c oxidase deficiency. AB - BACKGROUND: Assembly of cytochrome c oxidase (COX, complex IV, cIV), the terminal component of the mitochondrial respiratory chain, is assisted by several factors, most of which are conserved from yeast to humans. However, some of them, including COA7, are found in humans but not in yeast. COA7 is a 231aa-long mitochondrial protein present in animals, containing five Sel1-like tetratricopeptide repeat sequences, which are likely to interact with partner proteins. METHODS: Whole exome sequencing was carried out on a 19 year old woman, affected by early onset, progressive severe ataxia and peripheral neuropathy, mild cognitive impairment and a cavitating leukodystrophy of the brain with spinal cord hypotrophy. Biochemical analysis of the mitochondrial respiratory chain revealed the presence of isolated deficiency of cytochrome c oxidase (COX) activity in skin fibroblasts and skeletal muscle. Mitochondrial localization studies were carried out in isolated mitochondria and mitoplasts from immortalized control human fibroblasts. RESULTS: We found compound heterozygous mutations in COA7: a paternal c.410A>G, p.Y137C, and a maternal c.287+1G>T variants. Lentiviral-mediated expression of recombinant wild-type COA7 cDNA in the patient fibroblasts led to the recovery of the defect in COX activity and restoration of normal COX amount. In mitochondrial localization experiments, COA7 behaved as the soluble matrix protein Citrate Synthase. CONCLUSIONS: We report here the first patient carrying pathogenic mutations of COA7, causative of isolated COX deficiency and progressive neurological impairment. We also show that COA7 is a soluble protein localized to the matrix, rather than in the intermembrane space as previously suggested. PMID- 27683826 TI - Oropharyngeal dysphagia and related factors in post-cardiac surgery: a systematic review. AB - Purpose: To identify the main factors associated with oropharyngeal dysphagia following cardiac surgery through a systematic review of the literature. Methods: A bibliographic search was conducted in the PubMed and ScienceDirect databases using the following keywords: "cardiac surgery", "deglutition disorders", and "dysphagia". Selection criteria: Articles published in Portuguese, English, or Spanish addressing oropharyngeal dysphagia following cardiac surgery were selected with no time limitation. Only studies available in full were included. Data analysis: First, articles were screened for title and abstract. Subsequently, they were submitted to full assessment by two blinded referees. The following data were extracted: authors, year of publication, study design, sample size, variables evaluated, and main results. Results: The main factors related to oropharyngeal dysphagia in post-cardiac surgery were advanced age, presence of comorbidities and other diseases, intubation time, and surgical conditions. Conclusion: The studies showed high heterogeneity, demonstrating that individuals who undergo cardiac surgical procedures, especially the elderly, present several factors related to oropharyngeal dysphagia postoperatively, such as cardiopulmonary bypass, transesophageal echocardiography, associated comorbidities, development of postoperative sepsis, and previous heart conditions. PMID- 27683822 TI - Cigarette Smoking and Inflammation, Monocyte Activation, and Coagulation in HIV Infected Individuals Receiving Antiretroviral Therapy, Compared With Uninfected Individuals. AB - Smoking may affect cardiovascular disease risk more strongly in human immunodeficiency virus (HIV)-infected individuals than HIV-uninfected individuals. We hypothesized that an interaction at the level of the immune system may contribute to this increased risk. We assessed soluble markers of inflammation (high-sensitivity C-reactive protein [hsCRP]), immune activation (soluble [s]CD14 and sCD163), and coagulation (D-dimer) in HIV-infected and uninfected never, former, and current smokers. Smoking was independently associated with higher hsCRP levels and lower sCD163 levels and was borderline significantly associated with higher sCD14 and D-dimer levels. We found no evidence of a differential effect of smoking in HIV-infected individuals as compared to uninfected individuals. PMID- 27683827 TI - Relationship between perception of tongue position and measures of tongue force on the teeth. AB - Purpose: To verify whether there are differences of tongue force on the teeth at rest and during swallowing between individuals who report appropriate tongue position and those who report tongue thrust. Methods: Tongue forces on the teeth were evaluated in 28 participants aged 19 to 31 years. To this end, a Flexiforce(r) resistive sensor was fixed to the palatal surface of the maxillary right central incisor (tooth 8) and was connected to an amplifier circuit, a data acquisition board, and a computer. Measurements were taken at rest and during saliva swallowing. Participants were asked about their habitual tongue position and where the apex of tongue touched when they swallowed. The Mann Whitney test was used for statistical analysis at 5% significance level. Results: At habitual position, tongue force on the teeth was 0.00 N both for participants that reported tongue touch and for those who did not. At directed swallowing, tongue force was 0.34 N for the group of individuals whose tongues touch the teeth and 0.08 N for the group of individuals whose tongues do not touch the teeth. This difference was significant. Conclusion: No significant difference was found between the tongue forces of participants of both groups at habitual position. However, participants with tongue thrust during directed swallowing presented greater force than those whose tongues do not touch the teeth during this task. PMID- 27683829 TI - Performance of children at risk for reading difficulties submitted to an intervention program. AB - Purpose: To assess the applicability of an intervention program to children at risk for reading disabilities. Methods: This experimental study compared 10 children at risk for reading difficulty submitted to a phonological decoding intervention program (study group) with 10 other children at risk for reading difficulty not submitted to the program (control group). The intervention program was based on two international studies. It comprised 24 sessions: the first 12 sessions were conducted with groups of two to three children, whereas the others were performed individually. The sessions lasted 50 minutes and were held twice a week. Statistical analysis was conducted using the Student's t-test and the Wilcoxon Signed-Rank test. Results: Children at risk for reading difficulties submitted to the phonological decoding intervention program showed statistically significant improvement at post-assessment in the performance of the following skills: letter naming; phoneme-grapheme relationship; phonological awareness; phonological working memory for non-words; phonological working memory for digits in direct order; alphabet recognition in sequence; writing under dictation of words and pseudowords; reading of words and pseudowords. Conclusion: The phonological decoding intervention program showed applicability to improve the prerequisite skills of reading and writing of children at risk for reading disabilities. PMID- 27683828 TI - Primary care health professionals' perception and knowledge on notification of noise-induced hearing loss in Curitiba - Parana. AB - Objective: The article aims to analyze the perception and knowledge of health professionals working in primary health care networks in the Municipality of Curitiba - Parana, regarding the compulsory notification of Induced Hearing Loss Noise (NIHL) in the National Notifiable Diseases Information System (SINAN). Methods: We performed a transversal cohort study in Curitiba, analyzing perception and knowledge of health professionals working in the primary health care networks in the Municipality of Curitiba, regarding the compulsory notification of NIHL in SINAN, from 2007 to 2014, featuring the reported cases and exploring the situational analysis of the NIHL notification, through a questionnaire and a structured news conference. Results: The primary care professionals' survey showed that 50% were doctors and the predominant age group was 26-30 years, with 56.2% reported as being able to identify health problems related to work, but only 43.7% feel able to identify cases of NIHL. Conclusion: It was found that health professionals know the features and feel able to identify cases of NIHL, but still do not report suspected NIHL cases and do not consider occupational health an institutionalized program that is part of the service. PMID- 27683830 TI - Cultural adaptation of the Test of Narrative Language (TNL) into Brazilian Portuguese. AB - Purpose: To accomplish the translation and cultural adaptation of the Test of Narrative Language (TNL) into Brazilian Portuguese. Methods: The TNL is a formal instrument which assesses narrative comprehension and oral narration of children between the ages of 5-0 and 11-11 (years-months). The TNL translation and adaptation process had the following steps: (1) translation into the target language; (2) summary of the translated versions; (3) back-translation; (4) checking of the conceptual, semantics and cultural equivalence process and (5) pilot study (56 children within the test age range and from both genders). Results: The adapted version maintained the same structure as the original version: number of tasks (both, three comprehension and oral narration), narrative formats (no picture, sequenced pictures and single picture) and scoring system. There were no adjustments to the pictures. The "McDonald's Story" was replaced by the "Snack Bar History" to meet the semantic and experiential equivalence of the target population. The other stories had semantic and grammatical adjustments. Statistically significant difference was found when comparing the raw score (comprehension, narration and total) of age groups from the adapted version. Conclusion: Adjustments were required to meet the equivalence between the original and the translated versions. The adapted version showed it has the potential to identify differences in oral narratives of children in the age range provided by the test. Measurement equivalence for validation and test standardization are in progress and will be able to supplement the study outcomes. PMID- 27683831 TI - Letter to the editors. PMID- 27683832 TI - Effects of rapid maxillary expansion in cleft patients resulting from the use of two different expanders. AB - Objective:: The aim of this study was to evaluate the skeletal and dental effects of rapid maxillary expansion (RME) in cleft patients using two types of expanders. Methods:: Twenty unilateral cleft lip and palate patients were randomly divided into two groups, according to the type of expander used: (I) modified Hyrax and (II) inverted Mini-Hyrax. A pretreatment cone-beam computed tomographic image (T0) was taken as part of the initial orthodontic records and three months after RME, for bone graft planning (T1). Results:: In general, there was no significant difference among groups (p > 0.05). Both showed a significant transverse maxillary expansion (p < 0.05) and no significant forward and/or downward movement of the maxilla (p > 0.05). There was greater dental crown than apical expansion. Maxillary posterior expansion tended to be larger than anterior opening (p < 0.05). Cleft and non-cleft sides were symmetrically expanded and there was no difference in dental tipping between both sides (p > 0.05). Conclusions:: The appliances tested are effective in the transverse expansion of the maxilla. However, these appliances should be better indicated to cleft cases also presenting posterior transverse discrepancy, since there was greater expansion in the posterior maxillary region than in the anterior one. PMID- 27683833 TI - Risk of falls in Brazilian elders with and without low back pain assessed using the Physiological Profile Assessment: BACE study. AB - Background: Low back pain (LBP) is a common musculoskeletal condition among elders and is associated with falls. However, the underlying biological risk factors for falling among elders with LBP has been poorly investigated. The Physiological Profile Assessment (PPA) is a validated fall-risk assessment tool that involves the direct assessment of sensorimotor abilities and may contribute to the understanding of risk factors for falls among elders with LBP. Objective: To assess fall risk using the PPA in elders with and without LBP. Method: This is an observational, comparative, cross-sectional study with elders aged >=65 years. The present study was conducted with a subsample of participants from the Back Complaints in the Elders (BACE) - Brazil study. Fall risk was assessed using the PPA, which contains five tests: visual contrast sensitivity, hand reaction time, quadriceps strength, lower limb proprioception, and postural sway. Results: Study participants included 104 individuals with average age of 72.3 (SD=4.0) years, divided into two groups: GI) 52 participants with LBP; GII) 52 participants without LBP. The participants with LBP had a significantly higher fall risk (1.10 95% CI 0.72 to 1.48), greater postural sway (49.78 95% CI 13.54 to 86.01), longer reaction time (58.95 95% CI 33.24 to 84.65), and lower quadriceps strength (-4.42 95% CI -8.24 to -0.59) compared to asymptomatic participants. There was no significant difference for vision and proprioception tests between LBP and non LBP participants. Conclusion: Elders with LBP have greater risk for falls than those without LBP. Our results suggest fall-risk screening may be sensible in elders with LBP. PMID- 27683834 TI - Is handgrip strength normalized to body weight a useful tool to identify dynapenia and functional incapacity in post-menopausal women? AB - Objective: To investigate whether handgrip strength normalized to body weight could be a useful clinical tool to identify dynapenia and assess functional capacity in post-menopausal women. Method: A total of 136 postmenopausal women were recruited. Body composition (Dual Energy X-ray Absorptiometry [DEXA], Bio electrical Impedence Analysis [BIA]), grip strength (dynamometer) and functional capacity (senior fitness tests) were evaluated. Dynapenia was established according to a handgrip strength index (handgrip strength divided by body weight (BW) in Kg/KgBW) obtained from a reference population of young women: Type I dynapenic (<0.44 kg/KgBW) and type II dynapenic (<0.35 kg/KgBW). Results: The results show a positive correlation between handgrip strength index (in kg/KgBW) and alternate-step test (r=0.30, p<0.001), chair-stand test (r=0.25, p<0.005) and one-leg stance test (r=0.335, p<0.001). The results also showed a significant difference in non-dynapenic compared to type I dynapenic and type II dynapenic for the chair-stand test (Non-dynapenic: 12.0+/-3.0; Type I: 11.7+/-2.5; Type II: 10.3+/-3.0) (p=0.037 and p=0.005, respectively) and the one-leg stance test (Non dynapenic: 54.2+/-14.2; Type I: 43.8+/-21.4; Type II: 35.0+/-21.8) (p=0.030 and p=0.004, respectively). Finally, a significant difference was observed between type II dynapenic and non-dynapenic for the chair-stand test (p=0.032), but not with type I dynapenic. Conclusion: The results showed that handgrip strength was positively correlated with functional capacity. In addition, non-dynapenic women displayed a better functional status when compared to type I and type II dynapenic women. Thus, the determination of the handgrip strength thresholds could be an accessible and affordable clinical tool to identify people at risk of autonomy loss. PMID- 27683835 TI - Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life. AB - Objective: To compare the profiles of patients with chronic obstructive pulmonary disease (COPD) considered physically active or inactive according to different classifications of the level of physical activity in daily life (PADL). Method: Pulmonary function, dyspnea, functional status, body composition, exercise capacity, respiratory and peripheral muscle strength, and presence of comorbidities were assessed in 104 patients with COPD. The level of PADL was quantified with a SenseWear Armband activity monitor. Three classifications were used to classify the patients as physically active or inactive: 30 minutes of activity/day with intensity >3.2 METs, if age >=65 years, and >4 METs, if age <65 years; 30 minutes of activity/day with intensity >3.0 METs, regardless of patient age; and 80 minutes of activity/day with intensity >3.0 METs, regardless of patient age. Results: In all classifications, when compared with the inactive group, the physically active group had better values of anthropometric variables (higher fat-free mass, lower body weight, body mass index and fat percentage), exercise capacity (6-minute walking distance), lung function (forced vital capacity) and functional status (personal care domain of the London Chest Activity of Daily Living). Furthermore, patients classified as physically active in two classifications also had better peripheral and expiratory muscle strength, airflow obstruction, functional status, and quality of life, as well as lower prevalence of heart disease and mortality risk. Conclusion: In all classification methods, physically active patients with COPD have better exercise capacity, lung function, body composition, and functional status compared to physically inactive patients. PMID- 27683836 TI - Ultrasound imaging in women's arm flexor muscles: intra-rater reliability of muscle thickness and echo intensity. AB - Background: Different ultrasound parameters have been frequently used to assess changes associated with training, aging, immobilization, and neuromuscular diseases. However, an exploratory reliability analysis of the echo intensity (EI) and muscle thickness (MT) of the forearm flexors is scarce, especially in women. Objective: The purpose of the present study was to determine the intra-rater reliability of MT and EI assessed by ultrasound in young women. Method: Ultrasonographic MT and EI were acquired in the forearm flexors of 41 young women (22+/-2 yrs). Reliability was calculated using intraclass correlation coefficient (ICC2,1), standard error of measurement (SEM), coefficient of variation (CV), smallest detectable change (SDC), and Bland and Altman plot analysis. Results: ICC values for MT and EI were 0.88 (95% CI: 0.78-0.93). The SEM and CV values were lower than 10%. Bland and Altman analysis revealed that ultrasound mean differences were 0.27 mm (Limits of Agreement - LOA 95%: - 2.6 to 3.2 mm) and 0.09 a.u. (LOA 95%: - 10.9 to 10.7 a.u.). Conclusion: MT and EI assessed by ultrasonography in young women appear to be reliable and may be used to monitor changes in muscle mass induced by strength training when these changes exceed the precision of ultrasound. PMID- 27683837 TI - Effects of functional and analytical strength training on upper-extremity activity after stroke: a randomized controlled trial. AB - Objective: To investigate the effects of functional strengthening (using functional movements) and analytical strengthening (using repetitive movements) on level of activity and muscular strength gain in patients with chronic hemiparesis after stroke. Method: A randomized, assessor-blinded trial was conducted in a therapist-supervised home rehabilitation program. Twenty-seven patients with chronic stroke were randomly allocated one of two groups: functional strengthening (FS) (n=13) and analytical strengthening (AS) (n=14). Each group received a five-week muscle strengthening protocol (30 minutes per day, three times per week) including functional movements or analytical movements, respectively. Pre-, post-, and ten-month follow-up outcomes included the Upper-Extremity Performance Test (primary outcome), Shoulder and Grip Strength, Active Shoulder Range of Motion (ROM), the Fugl-Meyer Assessment, and the Modified Ashworth Scale (MAS) (secondary outcomes). Results: There was significant improvement in the Upper-Extremity Performance Test for the combined unilateral and bilateral task scores in the FS Group (mean difference 2.4; 95% CI=0.14 to 4.6) in the 10-month follow-up. No significant difference was observed between groups in the other outcomes (p>0.05). Conclusion: A five-week home-based functional muscle strengthening induced positive results for the upper-extremity level of activity of patients with moderate impairment after chronic stroke. PMID- 27683838 TI - Factors associated with attitudes and beliefs of elders with acute low back pain: data from the study Back Complaints in the Elders (BACE). AB - Background: The attitudes and beliefs that older people have about acute low back pain (LBP) may influence the coping mechanisms and the adoption of treatment strategies in this population. Objective: The aim of this study was to identify the factors associated with the attitudes and beliefs of elderly patients with acute low back pain using the Back Beliefs Questionnaire. Method: This is a cross sectional study with a subsample of the study "Back Complaints in the Elders" (BACE), composed of 532 older Brazilians of both genders with acute LBP. We investigated sociodemographic and clinical aspects, self-perceived health, psychosocial and emotional state, falls, and functional capacity. Multiple regression models were constructed to measure possible associations. Results: The percentage of female participants was 85.7% and the mean age was 69.04 (SD=6.2). Disability, symptoms of depression, and expectation of return to activities were independently associated with attitudes and beliefs concerning LBP. Conclusion: Screening of psychosocial factors is essential to the prevention of persistent and recurrent LBP. Early signs of these factors can help identify symptoms and behaviors for effective interventions. PMID- 27683839 TI - Effectiveness of a healthy lifestyle intervention for low back pain and osteoarthritis of the knee: protocol and statistical analysis plan for two randomised controlled trials. AB - Background: These trials are the first randomised controlled trials of telephone based weight management and healthy lifestyle interventions for low back pain and knee osteoarthritis. This article describes the protocol and statistical analysis plan. Method: These trials are parallel randomised controlled trials that investigate and compare the effect of a telephone-based weight management and healthy lifestyle intervention for improving pain intensity in overweight or obese patients with low back pain or knee osteoarthritis. The analysis plan was finalised prior to initiation of analyses. All data collected as part of the trial were reviewed, without stratification by group, and classified by baseline characteristics, process of care and trial outcomes. Trial outcomes were classified as primary and secondary outcomes. Appropriate descriptive statistics and statistical testing of between-group differences, where relevant, have been planned and described. Conclusions: A protocol for standard analyses was developed for the results of two randomised controlled trials. This protocol describes the data, and the pre-determined statistical tests of relevant outcome measures. The plan demonstrates transparent and verifiable use of the data collected. This a priori protocol will be followed to ensure rigorous standards of data analysis are strictly adhered to. PMID- 27683841 TI - Parasites of marine, freshwater and farmed fishes of Portugal: a review. AB - An extensive literature review is made of the parasites in marine and freshwater fish in mainland Portugal, the Portuguese archipelagos of the Azores and Madeira, as well as in farmed fish. The host(s) of each parasite species, its location in the host, site of capture of the host, whenever possible, and all the available bibliographic references are described. The economic importance of some parasites and the zoonotic relevance of some parasitic forms are discussed. A general overview of the data is provided, and some research lines are suggested in order to increase and complement the current body of knowledge about the parasites of fish from Portugal. PMID- 27683840 TI - Acute effects of Expiratory Positive Airway Pressure (EPAP) on different levels in ventilation and electrical activity of sternocleidomastoid and parasternal muscles in Chronic Obstructive Pulmonary Disease (COPD) patients: a randomized controlled trial. AB - Objective: To investigate the acute effects of EPAP on the activity of sternocleidomastoid (SCM), parasternal muscles and ventilatory parameters in COPD patients. Method: Twenty-four patients with COPD were studied using surface electromyography (sEMG) and a ventilometer. Patients were randomly assigned to EPAP 10 cmH2O-EPAP10 or 15 cmH2O-EPAP15 for 20 minutes. Results: The parasternal muscle sEMG activity increased during EPAP10 and EPAP15; however, a greater and significant increase was observed with EPAP10 (mean between-group difference: 12.5% RMS, 95% CI: 9.5 to 15.4, p<0.001). In relation to the baseline, at 10 and 20 minutes and upon recovery, respectively parasternal activity increased by 23.9%, 28.9% and 19.1% during EPAP10 and by 10.7% at 10 and 20 minutes and upon recovery, respectively, 11.4% and 6.9% during EPAP15 at 10 and 20 minutes and upon recovery, respectively. The sEMG activity of SCM muscle showed an opposite pattern, increasing with EPAP15 and decreasing with EPAP10 (mean between-group difference: 15.5% RMS, 95% CI: 12.6 to 18.4, p<0.001). SCM muscle activity during EPAP15, increased by 4.8% and 6.1% at 10 and 20 minutes and decreased by -4.0% upon recovery compared to decreases of -5.6%, -20.6% and -21.3% during EPAP10 at 10, 20 minutes, and recovery. Ventilation at both EPAP intensities promoted significant reductions in respiratory rate (RR) and dyspnea, more pronounced in EPAP15: RR (mean between-group difference: -3,8bpm, 95%CI: -7,5 to -0,2, p=0,015) and dyspnea (mean between-group difference: -1.01, 95%CI: -1.4 to -0.53, p=0.028) . Conclusion: In COPD patients, the use of EPAP10 was more effective in reducing accessory inspiratory activity and increasing parasternal activity, which was accompanied by an improvement in ventilation and a reduction in dyspnea. PMID- 27683842 TI - Post-immunization immunohistochemical expression of Caspase 3 and p53 apoptotic markers in experimental hydatidosis. AB - The aim of this study was to investigate post-immunization apoptotic changes in experimental hydatidosis, using Caspase 3 and p53 immunohistochemical markers. Two groups of rabbits were immunized with a crude antigen (group 1) or a partially purified antigen (group 2) and were compared to an infected non immunized control group. More effective immune responses were obtained in group 2 than group 1, signified by fewer and smaller cystic lesions and more severe destructive changes. Normal growth of cysts was attained in the control group, with no expression of apoptotic markers. Significantly higher expression of Caspase 3 and p53 were observed in group 1 compared to group 2, as indicated by OD and area percentage, respectively (Group 1 Caspase 3: 0.89+/-0.21, 93.5%+/ 6.2; Group 1 p53: 0.46+/-0.18, 53.26%+/-11.6; Group 2 Caspase 3: 0.52+/-0.15, 49.23%+/-11.7; Group 2 p53: 0.19+/-0.4, 18.17%+/-7.3). Vaccine-induced immune responses and cellular damage may underlie the expression of apoptotic markers that appeared to result in a degenerative and atrophic course of action upon immunization. The results of the current study emphasize the importance of immunization for the stimulation of protective immune responses and in preventing mechanisms of evasion to ensure normal cell growth. A cost/benefit control program that implements proper vaccine preparations should be further assessed for complete elimination of severe infections in endemic areas. PMID- 27683843 TI - Neurologic involvement in patients with atypical Chediak-Higashi disease. PMID- 27683844 TI - Switching generic antiepileptic drug manufacturer not linked to seizures: A case crossover study. AB - OBJECTIVE: With more antiepileptic drugs (AED) becoming available in generic form, we estimated the risk of seizure-related events associated with refilling generic AEDs and the effect of switching between different manufacturers of the same generic drug. METHODS: We designed a population-based case-crossover study using the Medicaid Analytic eXtract and a US commercial health insurance database. We identified 83,001 generic AED users who experienced a seizure related hospital admission or emergency room visit between 2000 and 2013 and assessed whether they received a refill of the same AED from the same manufacturer or a different manufacturer. Patients served as their own controls and conditional logistic regression was used to compare exposure to a refill during the hazard period, defined as days 2-36 preceding the seizure-related event, to exposure during the control period, defined as days 51-85 preceding the seizure-related event. RESULTS: Generic AED refilling was associated with an 8% increase in the odds of seizure-related events (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.06-1.11). The OR following a switch to a different manufacturer of the same AED was 1.09 (95% CI 1.03-1.15); however, after adjusting for the process of refilling, there was no association between switching and seizure-related hospital visits (OR 1.00; 95% CI 0.94-1.07). CONCLUSIONS: Among patients on a generic AED, refilling the same AED was associated with an elevated risk of seizure-related event; however, there was no additional risk from switching during that refill to a different manufacturer. Generic AEDs available to US patients, with Food and Drug Administration validated bioequivalence, appear to be safe clinical choices. PMID- 27683845 TI - Prevalence of polyneuropathy in the general middle-aged and elderly population. AB - OBJECTIVE: To determine the prevalence of chronic polyneuropathy in an unselected community-dwelling population of middle-aged and elderly people. METHODS: The current study was embedded in the prospective, population-based Rotterdam Study. Between June 2013 and October 2015, 1,310 participants (mean age 70 years, 55% female) were screened for the presence of polyneuropathy. This screening consisted of a questionnaire, neurologic examination, and nerve conduction studies. Polyneuropathy was diagnosed by a consensus panel that categorized participants into no, possible, probable, or definite polyneuropathy, depending on the level of abnormality of the screening. Medical records were scrutinized to evaluate whether the disorder was diagnosed before and laboratory investigations were performed to determine the presence of associated risk factors. RESULTS: Prevalence of definite polyneuropathy was 5.5% (95% confidence interval 4.4-6.9), age-standardized to the population of the Netherlands 4.0% (3.1-5.3). Prevalence was higher in male participants (6.7% compared to 4.5%) and increased with age. When combining probable and definite polyneuropathy, age-standardized prevalence was 9.4% (7.9-11.1). Almost half of the polyneuropathies (49%) were newly diagnosed. The majority of polyneuropathies were idiopathic (46%). Diabetes, present in 31% of participants with polyneuropathy, was the most commonly found risk factor. CONCLUSIONS: Prevalence of polyneuropathy in the general middle-aged and elderly population is at least 4%, and increases with age. Almost half of the cases were newly diagnosed, indicating that the presence of polyneuropathy is underreported or underdiagnosed. Currently, almost half of the polyneuropathies are idiopathic. Future prospective cohort studies should focus on identifying new determinants of polyneuropathy. PMID- 27683848 TI - Charter on Physician Professional Flourishing. AB - Medical care delivery has adapted to scientific and societal change in the past. However, today's advancing scientific accomplishments and care capabilities, in the context of current societal and economic developments and our emerging digital age, are challenging physician resilience and endurance and trust in the medical profession. Why has this happened and can these characteristics and perceptions of physicians be reversed? The Charter on Physician Professional Flourishing is a method designed to restore the promise of the medical profession and trust in it. It describes a process to reinvigorate patient-centered care from the caregiving physician's perspective. It integrates discipline ethics, behavioral character ethics, and optimized physician-patient dialogue, while considering past, current, and predicted future context and professional sustainability. Its primary outcomes are enhanced quality of care and cost containment and the ability to reassert the voice of the patient in health care planning negotiations. PMID- 27683846 TI - Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study. AB - OBJECTIVE: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. METHODS: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg.kg-1.d-1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg.kg-1.d-1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases >=40% and increasing seizure rates. RESULTS: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and >=75% responders demonstrated a consistent response over time. Few patients had a dosage increase >=40% associated with an increase in seizure rates. CONCLUSIONS: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. CLINICALTRIALSGOV IDENTIFIER: NCT00518713 and NCT01160770. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID- 27683847 TI - Cognitive reserve in frontotemporal degeneration: Neuroanatomic and neuropsychological evidence. AB - OBJECTIVE: To evaluate if cognitive reserve (CR) contributes to interindividual differences in frontal gray matter density (GMD) and executive impairment that underlie heterogeneity in the disease course of confirmed frontotemporal lobar degeneration (FTLD) pathology. METHODS: Fifty-five patients with autopsy confirmation or a pathogenic mutation consistent with underlying tau (FTLD-tau) or TDP-43 (FTLD-TDP) pathology and 90 demographically comparable healthy controls were assessed with T1 MRI and neuropsychological measures (Mini-Mental State Examination, letter fluency, forward digit span, Rey complex figure, and Boston Naming Test). CR was indexed using a composite measure of education and occupation. We used t tests to identify reduced GMD in patients with FTLD relative to controls, regression analyses to relate reduced GMD to CR index, and correlations to relate regions of GMD associated with CR to performance on neuropsychological measures. RESULTS: Patients with FTLD demonstrated impairment on neuropsychological measures. Patients with FTLD exhibited reduced bilateral frontotemporal GMD relative to controls, consistent with the known anatomic distribution of FTLD pathology. Higher CR index was associated with superior letter fluency and with GMD in right dorsolateral prefrontal cortex, orbitofrontal cortex, rostral frontal cortex, and inferior frontal gyrus. Furthermore, we found that higher GMD in frontal regions associated with CR was associated with superior letter fluency. CONCLUSIONS: Executive control and verbal ability assessed by letter fluency in FTLD is mediated in part by CR and frontal GMD. The identification of factors influencing cognitive and anatomic heterogeneity in FTLD suggests that CR should be considered in symptom detection, prognosis, and treatment. PMID- 27683849 TI - More data on the safety of generic substitution: Yes, the blue tablet is OK? PMID- 27683850 TI - Relative effect of APOE epsilon4 on neuroimaging biomarker changes across the lifespan. AB - OBJECTIVE: To provide a comprehensive understanding of APOE epsilon4 effects across the lifespan on the 3 main neuroimaging biomarkers. METHODS: Two hundred seven community-dwelling, cognitively normal APOE epsilon4 carriers and noncarriers aged 20-87 years were involved in this study. They underwent structural MRI, fluorodeoxyglucose-PET, and florbetapir-PET scans. The effects of APOE, age, and APOE * age interaction were assessed voxel-wise for each modality. RESULTS: There was no significant effect of APOE or APOE * age interaction on gray matter volume and glucose metabolism, although decreases with age tended to be stronger in noncarriers than in carriers. In contrast, beta-amyloid (Abeta) deposition was significantly higher in carriers compared with noncarriers in a largely distributed network, and there was a significant APOE * age interaction such that Abeta deposition increased nonlinearly with age in APOE epsilon4 carriers only. CONCLUSIONS: Our findings highlight a differential effect of APOE epsilon4 on amyloid vs neurodegeneration biomarkers. APOE epsilon4 mainly influences Abeta deposition, while the effects on gray matter volume and glucose metabolism are at best subtle. CLINICALTRIALSGOV IDENTIFIER: NCT01638949. PMID- 27683851 TI - Posterior interosseous neuropathy: Supinator syndrome vs fascicular radial neuropathy. AB - OBJECTIVE: To investigate the spatial pattern of lesion dispersion in posterior interosseous neuropathy syndrome (PINS) by high-resolution magnetic resonance neurography. METHODS: This prospective study was approved by the local ethics committee and written informed consent was obtained from all patients. In 19 patients with PINS and 20 healthy controls, a standardized magnetic resonance neurography protocol at 3-tesla was performed with coverage of the upper arm and elbow (T2-weighted fat-saturated: echo time/repetition time 52/7,020 milliseconds, in-plane resolution 0.27 * 0.27 mm2). Lesion classification of the radial nerve trunk and its deep branch (which becomes the posterior interosseous nerve) was performed by visual rating and additional quantitative analysis of normalized T2 signal of radial nerve voxels. RESULTS: Of 19 patients with PINS, only 3 (16%) had a focal neuropathy at the entry of the radial nerve deep branch into the supinator muscle at elbow/forearm level. The other 16 (84%) had proximal radial nerve lesions at the upper arm level with a predominant lesion focus 8.3 +/- 4.6 cm proximal to the humeroradial joint. Most of these lesions (75%) followed a specific somatotopic pattern, involving only those fascicles that would form the posterior interosseous nerve more distally. CONCLUSIONS: PINS is not necessarily caused by focal compression at the supinator muscle but is instead frequently a consequence of partial fascicular lesions of the radial nerve trunk at the upper arm level. Neuroimaging should be considered as a complementary diagnostic method in PINS. PMID- 27683852 TI - Physical activity and the incidence of multiple sclerosis. AB - OBJECTIVE: To study whether physical activity during adulthood or early life is associated with multiple sclerosis (MS) incidence in 2 prospective cohorts of women. METHODS: Women in the Nurses' Health Study (NHS) (n = 81,723; 1986-2004) and NHS II (n = 111,804; 1989-2009) reported recent physical activity at baseline and in selected follow-up questionnaires. Using this information, we calculated total metabolic equivalent hours of physical activity per week, a measure of energy expenditure. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. To estimate relative rates (RRs) and 95% confidence intervals (CIs), we used Cox proportional hazards models, adjusting for age, latitude of residence at age 15, ethnicity, smoking, supplemental vitamin D, and body mass index at age 18. RESULTS: Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS (RRpooled = 0.73, 95% CI 0.55-0.98; p-trend 0.08); this trend was not present in 6-year lagged analyses. Change in physical activity analyses suggested that women reduced activity before onset of MS symptoms. In NHS and NHS II, higher strenuous activity at ages 18-22 years was weakly associated with a decreased MS rate. However, in NHS II, total early-life activity at ages 12-22 was not associated with MS. CONCLUSIONS: Though higher physical activity at baseline was weakly associated with lower MS risk, this may have been due to women reducing physical activity in response to subclinical MS. PMID- 27683854 TI - The uses of history and of philosophy within psychiatry. PMID- 27683853 TI - The urgent need for contemporary clinical trials in patients with asymptomatic carotid stenosis. AB - Asymptomatic extracranial internal carotid artery atherosclerotic stenosis increases with age and is more common in men. Studies performed more than 2 decades ago showed that carotid endarterectomy reduced the rate of stroke in carefully selected patients with asymptomatic carotid stenosis compared with medical therapy in the long term. Those trials were completed more than 20 years ago and with advances in the treatment of atherosclerotic disease, the question has been raised to as to whether endarterectomy is still of value for patients with asymptomatic narrowing. Perioperative risk of carotid revascularization procedures has also declined. Due to improvements in both medical and surgical treatments for carotid artery stenosis, it is timely to reevaluate the efficacy of carotid intervention relative to medical treatment for patients with asymptomatic stenosis. PMID- 27683855 TI - John Cade and the biographer's art. PMID- 27683856 TI - RANZCP Advocacy and the New Fellows. PMID- 27683857 TI - Developing leadership competencies among medical trainees: five-year experience at the Cleveland Clinic with a chief residents' training course. AB - OBJECTIVES: Challenges in healthcare demand great leadership. In response, leadership training programs have been developed within academic medical centers, business schools, and healthcare organizations; however, we are unaware of any well-developed programs for physicians-in-training. METHODS: To address this gap, we developed a two-day leadership development course for chief residents (CRs) at the Cleveland Clinic, framed around the concept of emotional intelligence. This paper describes our five-year experience with the CRs leadership program. RESULTS: Since inception, 105 CRs took the course; 81 (77%) completed before-and after evaluations. Participants indicated that they had relatively little prior knowledge of the concepts that were presented and that the workshop greatly enhanced their familiarity with leadership competencies. Qualitative analysis of open-ended responses indicated that attendees valued the training, especially in conflict resolution and teamwork, and indicated specific action plans for applying these skills. Furthermore, the workshop spurred some participants to express plans to learn more about leadership competencies. CONCLUSIONS: This study extends prior experience in offering an emotional intelligence-based leadership workshop for CRs. Though the program is novel, further research is needed to more fully understand the impact of leadership training for CRs and for the institutions and patients they serve. PMID- 27683858 TI - Critical appraisal. PMID- 27683860 TI - Smoke-free acute psychiatric settings are a safe and ethical public health intervention. PMID- 27683861 TI - Context matters: communicating the need for biomarkers for mental illnesses to the general public. PMID- 27683863 TI - From the President. PMID- 27683865 TI - Talking with Dr Philip Mosley. PMID- 27683862 TI - Drug and alcohol management in Australia. PMID- 27683869 TI - SNAP-Ed (Supplemental Nutrition Assistance Program-Education) Increases Long-Term Food Security among Indiana Households with Children in a Randomized Controlled Study. AB - BACKGROUND: Food insecurity is negatively associated with US children's dietary intake and health. The Supplemental Nutrition Assistance Program-Education (SNAP Ed) aims to alleviate food insecurity by offering nutrition, budgeting, and healthy lifestyle education to low-income individuals and families. OBJECTIVE: The objective of this study was to evaluate the long-term impact of the Indiana SNAP-Ed on food security among households with children. METHODS: A randomized, controlled, parallel study design with SNAP-Ed as an intervention was carried out during a 4- to 10-wk intervention period. Intervention group participants received the first 4 Indiana SNAP-Ed curriculum lessons. Study participants (n = 575) were adults aged >=18 y from low-income Indiana households with >=1 child living in the household. Both treatment groups completed an assessment before and after the intervention period and 1 y after recruitment. The 18-item US Household Food Security Survey Module was used to classify the primary outcomes of food security for the household and adults and children in the household. A linear mixed model was used to compare intervention with control group effects over time on food security. RESULTS: Mean +/- SEM changes in household food security score and food security score among household adults from baseline to 1-y follow-up were 1.2 +/- 0.4 and 0.9 +/- 0.3 units lower, respectively, in the intervention group than in the control group (P < 0.01). The mean change in food security score from baseline to 1-y follow-up among household children was not significantly different in the intervention group compared with the control group. CONCLUSIONS: SNAP-Ed improved food security over a longitudinal time frame among low-income Indiana households with children in this study. SNAP-Ed may be a successful intervention to improve food security. PMID- 27683868 TI - Stunting in Infancy Is Associated with Decreased Risk of High Body Mass Index for Age at 8 and 12 Years of Age. AB - BACKGROUND: Effects of early-life stunting on adiposity development later in childhood are not well understood, specifically with respect to age in the onset of overweight and obesity. OBJECTIVES: We analyzed associations of infant stunting with prevalence of, incidence of, and reversion from high body mass index-for-age z score (BMIZ) later in life. We then estimated whether associations of infant stunting with BMIZ varied by sex, indigenous status, and rural or urban residence. METHODS: Data were collected from 1942 Peruvian children in the Young Lives cohort study at ages 1, 5, 8, and 12 y. Multivariable generalized linear models estimated associations of stunting (height-for-age z score <-2) at age 1 y with risk of BMIZ > 1 and BMIZ > 2 prevalence, incidence (moving above a BMIZ threshold between ages), and reversion (moving below a BMIZ threshold between ages) at later ages. RESULTS: After adjustment for covariates, stunting at age 1 y was associated with a lower prevalence of BMIZ > 1 at age 8 y (RR: 0.81; 95% CI: 0.66, 1.00; P = 0.049) and 12 y (RR: 0.75; 95% CI: 0.61, 0.91; P = 0.004), as well as a lower prevalence of BMIZ > 2 at age 8 y. Stunting was not associated with incident risk of BMIZ > 1 or BMIZ > 2. Stunting was positively associated at age 5 y with risk of reversion from BMIZ > 1 (RR: 1.22; 95% CI: 1.05, 1.42; P = 0.008) and BMIZ > 2. We found evidence that the association of stunting with prevalent and incident BMIZ > 1 was stronger for urban children at ages 5 and 8 y, and for nonindigenous children at age 8 y. CONCLUSIONS: Stunting predicted a lower risk of prevalent BMIZ > 1 and BMIZ > 2, even after controlling for potential confounders. This finding may be driven in part by a higher risk of reversion from BMIZ > 1 by age 5 y. Our results contribute to an understanding of how nutritional stunting in infancy is associated with BMIZ later in life. PMID- 27683870 TI - Retinol Isotope Dilution Is Applied during Restriction of Vitamin A Intake to Predict Individual Subject Total Body Vitamin A Stores at Isotopic Equilibrium. AB - BACKGROUND: Retinol isotope dilution (RID) equations are used to determine vitamin A status and the efficacy of vitamin A intervention programs. Recent work related to RID methods has focused on modifying the "Olson equation" to improve the accuracy of predictions of vitamin A total body stores (TBS) in individual subjects. OBJECTIVE: We investigated the hypothesis that short-term restriction of vitamin A intake would result in accurate RID prediction of vitamin A TBS in individuals. METHODS: We applied model-based compartmental analysis to a 6 component model derived from published retinol kinetic studies on 12 individuals with a wide range of vitamin A stores and determined vitamin A TBS in the steady state. Then we simulated the impact of eliminating or strictly limiting vitamin A intake at the time of isotope administration, while maintaining plasma retinol homeostasis, on retinol specific activity in plasma (SAp; fraction of dose/MUmol retinol) and stores, and we calculated TBS using the simplified RID equation TBS = 0.75 * 1/SAp, where the fractional absorption of tracer was set at 0.75 and SAp was simulated 5 d after dosing. RESULTS: When vitamin A intake was zero or strictly limited (0.25 MUmol/d), mean TBS predicted by the equation at 5 d after dose administration divided by TBS determined by using the model was 1.00 (range: 0.959-1.04) or 1.02 (range: 0.983 - 1.06), respectively. CONCLUSIONS: By eliminating or strictly limiting vitamin A input, isotopic equilibrium was reached by 5 d. At isotopic equilibrium, SAp is the same as that in the body's exchangeable vitamin A pools; under these conditions, SAp may be measured at any time from 5 d on and used to calculate TBS. PMID- 27683871 TI - A Dietary Supply of Docosahexaenoic Acid Early in Life Is Essential for Immune Development and the Establishment of Oral Tolerance in Female Rat Offspring. AB - BACKGROUND: The early postnatal period is critical for immunity, and feeding docosahexaenoic acid (DHA) has been demonstrated to affect immune development. OBJECTIVE: The objective of this study was to determine the importance of feeding DHA during suckling and/or weaning on immune function and oral tolerance (OT). METHODS: Sprague-Dawley rats were randomly assigned to 1 of 2 nutritionally adequate diets throughout lactation (21 d): a control (n = 12, 0% DHA) diet or a DHA (n = 8, 0.9% DHA) diet. At 11 d, suckled pups from each dam were randomly assigned to a mucosal OT challenge: placebo or ovalbumin. At week 5, all pups systemically received ovalbumin + adjuvant to induce systemic immunization. At 21 d, pups from each dam were randomly assigned to 1 of the 2 diets for 21 d in a factorial design after which immune function and OT were assessed. RESULTS: Feeding dams DHA during lactation resulted in a 40-60% higher splenocyte production of interleukin (IL)-10 when stimulated with concanavalin A, lipopolysaccharide (LPS), or ovalbumin and a 100% higher production of interferon (IFN)-gamma with LPS (P < 0.05) than feeding the control diet to the pups. In comparison with pups fed the control diet, feeding DHA at weaning resulted in a 25% lower type 1 T helper (IL-1beta) and type 2 T helper (IL-6) response by splenocytes after LPS stimulation and a 33% lower plasma concentration of ovalbumin-specific immunoglobulin (Ig) G (P < 0.05). Pups that did not receive additional DHA during the study had a 70% higher plasma concentration of ovalbumin-specific IgE than did the pups that received DHA at suckling and/or weaning (P < 0.05). CONCLUSIONS: Feeding additional DHA during suckling had a beneficial programming effect on the ability of immune cells to produce IFN-gamma and IL-10, and feeding DHA during weaning resulted in a lower inflammatory response. Providing no dietary DHA in either of the critical periods of immune development prevented the establishment of OT in female rat offspring. PMID- 27683872 TI - Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25 Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults. AB - BACKGROUND: Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation. OBJECTIVE: This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial. METHODS: Eligible older adults who were not vitamin D deficient [serum 25(OH)D >=12 ng/mL] were randomly assigned in a modified 2 * 2 factorial design to 1 of 4 groups: daily 1000 IU cholecalciferol, 1200 mg Ca as carbonate, both, or placebo. Women could elect 2-group (calcium +/- cholecalciferol) random assignment. In secondary analyses, we used multivariable models to assess factors associated with serum 25(OH)D concentrations in all enrollees (n = 2753) and with relative changes in serum 25(OH)D after 1 y cholecalciferol supplementation among those randomly assigned (n = 2187). RESULTS: In multivariable models, 8 factors accounted for 50% of the variability of proportional change in serum 25(OH)D after cholecalciferol supplementation. Larger increases were associated with being female (34.5% compared with 20.5%; P < 0.001) and with lower baseline serum 25(OH)D (P < 0.0001), optimal adherence to study pill intake (P = 0.0002), wearing long pants and sleeves during sun exposure (P = 0.0002), moderate activity level (P = 0.01), use of extra vitamin D containing supplements during the trial (P = 0.03), and seasons of blood draw (P <= 0.002). Several genetic polymorphisms were associated with baseline serum 25(OH)D and/or serum response, but these did not substantially increase the models' R2 values. Other factors, including body mass index, were associated with serum 25(OH)D at baseline but not with its response to supplemental cholecalciferol. CONCLUSIONS: The factors that most affected changes in serum 25(OH)D concentrations in response to cholecalciferol supplementation included sex, baseline serum 25(OH)D, supplement intake adherence, skin-covering clothes, physical activity, and season. Genetic factors did not play a major role. This trial was registered at www.clinicaltrials.gov as NCT00153816. PMID- 27683873 TI - Maternal Dietary Patterns during Pregnancy Are Associated with Child Growth in the First 3 Years of Life. AB - BACKGROUND: Child obesity is a major problem in the United States. Identifying early-life risk factors is necessary for prevention. Maternal diet during pregnancy is a primary source of fetal energy and might influence risk of child obesity. OBJECTIVE: We prospectively investigated the influence of maternal dietary patterns during pregnancy on child growth in the first 3 y of life in 389 mother-child pairs from the Pregnancy, Infection, and Nutrition study. METHODS: Dietary patterns were derived with the use of latent class analysis (LCA) based on maternal diet, collected with the use of a food-frequency questionnaire at 26 29 wk gestation. Associations between maternal dietary patterns and child body mass index (BMI)-for-age z score and overweight or obesity were assessed with the use of linear regression and log-binomial regression, respectively. We used linear mixed models to estimate childhood growth patterns in relation to maternal dietary patterns. RESULTS: Three patterns were identified from LCA: 1) fruits, vegetables, refined grains, red and processed meats, pizza, french fries, sweets, salty snacks, and soft drinks (latent class 1); 2) fruits, vegetables, baked chicken, whole-wheat bread, low-fat dairy, and water (latent class 2); and 3) white bread, red and processed meats, fried chicken, french fries, and vitamin C rich drinks (latent class 3). In crude analyses, the latent class 3 diet was associated with a higher BMI-for-age z score at 1 and 3 y of age and a higher risk of overweight or obesity at 3 y of age than was the latent class 2 diet. These associations were not detectable after adjustment for confounding factors. We observed an inverse association between the latent class 3 diet and BMI-for age z score at birth after adjustment for confounding factors that was not evident in the crude analysis (latent class 3 compared with latent class 2-beta: 0.41; 95% CI: -0.79, -0.03). CONCLUSION: In this prospective study, a less healthy maternal dietary pattern was associated with early childhood weight patterns. PMID- 27683875 TI - Subjective health complaints, work-related stress and self-efficacy in Norwegian aircrew. AB - Background: The European civilian aviation industry has undergone major changes in the last decade. Despite this, there is little knowledge about work-related stress and subjective health complaints (SHCs) affecting Norwegian aircrew. Aims: To investigate the relationships between work-related stress, self-efficacy and SHCs in commercial aircrew in Norway and to explore differences between cockpit and cabin crew. Methods: Aircrew members from the three major airlines operating from Norway completed an electronically distributed questionnaire. Linear regression analyses were used to investigate the association between work-related stress, self-efficacy and SHCs. Results: There was a 21% response rate. Among the 843 study subjects, tiredness, sleep problems, bloating, low back pain, headaches and neck pain were the most prevalent SHCs. Cabin crew reported significantly higher numbers, prevalences and mean values for all SHCs compared with cockpit crew (P < 0.05). In total, 20% reported high stress levels. High levels of work related stress were significantly associated with all SHC factors in both groups. Self-efficacy partly moderated the relationship between stress and psychological complaints in both cockpit and cabin crew, and for musculoskeletal complaints in cockpit crew. The model explained 23 and 32% of the variance in psychological complaints for cockpit and cabin crew, respectively. Conclusions: Commercial aircrew in Norway reported high numbers of SHCs, and high levels of work-related stress were associated with high numbers of SHC. More knowledge is needed on the physical, organizational and psychosocial stressors affecting cockpit and cabin crew in order to create a healthier work environment for these groups. PMID- 27683876 TI - Anti-Sulfoglucuronosyl Paragloboside Antibody: A Potential Serologic Marker of Amyotrophic Lateral Sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC). Anti-SGPG antibodies were found in the sera of 13.3% ALS patients (15 out of 113). The highest titer reached 1:1600. The presence of anti-SGPG antibodies in the serum samples was also confirmed by immuno-TLC. Importantly, a multiple logistic regression analysis showed that the presence of anti-SGPG antibody was positively correlated with age (p < .01) and negatively correlated with ALS Functional Rating Scale score (p < .05). Moreover, the localization of SGPG-immunoreactivity on the motor neurons of rat spinal cord and a mouse motor neuronal cell line, NSC-34 was observed by an immunofluorescence method. These data suggest that SGPG could represent a specific pathogenic antigen in those ALS patients. The presence of anti-SGPG antibodies in the serum of ALS patients should represent a diagnostic biomarker of ALS, and it could reflect the severity of the disease. PMID- 27683874 TI - Cocoa Flavanol Intake and Biomarkers for Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Cocoa flavanols may improve cardiometabolic health. Evidence from small short-term randomized clinical trials (RCTs) remains inconsistent, and large long-term RCTs testing the efficacy of cocoa flavanols are still lacking. OBJECTIVE: We performed a systematic review and meta-analysis of RCTs to quantify the effect of cocoa flavanol intake on cardiometabolic biomarkers. METHODS: We searched PubMed, Web of Science, and the Cochrane Library for RCTs that evaluated the effects of cocoa flavanols on biomarkers relevant to vascular disease pathways among adults. Data were extracted following a standardized protocol. We used DerSimonian and Laird random-effect models to compute the weighted mean differences (WMDs) and 95% CIs. We also examined potential modification by intervention duration, design, age, sex, comorbidities, and the form and amount of cocoa flavanol intake. RESULTS: We included 19 RCTs that comprised 1131 participants, and the number of studies for a specific biomarker varied. The amount of cocoa flavanols ranged from 166 to 2110 mg/d, and intervention duration ranged from 2 to 52 wk. Cocoa flavanol intake significantly improved insulin sensitivity and lipid profile. The WMDs between treatment and placebo were -0.10 mmol/L (95% CI: -0.16, -0.04 mmol/L) for total triglycerides, 0.06 mmol/L (95% CI: 0.02, 0.09 mmol/L) for HDL cholesterol, -2.33 MUIU/mL (95% CI: -3.47, -1.19 MUIU/mL) for fasting insulin, -0.93 (95% CI: -1.31, -0.55) for the homeostatic model assessment of insulin resistance, 0.03 (95% CI: 0.01, 0.05) for the quantitative insulin sensitivity check index, 2.54 (95% CI: 0.63, 4.44) for the insulin sensitivity index, -0.83 mg/dL (95% CI: -0.88, -0.77 mg/dL) for C reactive protein, and 85.6 ng/mL (95% CI: 16.0, 155 ng/mL) for vascular cell adhesion molecule 1. No significant associations were found for other biomarkers. None of the modifiers seemed to qualitatively modify the effects of cocoa flavanol intake. CONCLUSIONS: Our study suggests that cocoa flavanol intake has favorable effects on select cardiometabolic biomarkers among adults. These findings support the need for large long-term RCTs to assess whether cocoa flavanol intake reduces the risk of diabetes and cardiovascular events. PMID- 27683877 TI - Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy. AB - Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNbeta) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2). Intranasal administration of human recombinant IFNbeta occurred 2 hr after HIE and infarct volume, body weight, neurobehavioral tests, histology, immunohistochemistry, brain water content, blood-brain barrier permeability, enzyme-linked immunosorbent assay, and Western blot were all used to evaluate various parameters. The results showed that both IFNbeta and the Type 1 interferon receptor expression decreases after HIE. Intranasal administration of human recombinant IFNbeta was able to be detected in the central nervous system and was able to reduce brain infarction volumes and improve neurological behavior tests 24 hr after HIE. Western blot analysis also revealed that human recombinant IFNbeta treatment stimulated Stat3 and Bcl-2 expression leading to a decrease in cleaved caspase-3 expression after HIE. Positive Fluoro-Jade C staining also demonstrated that IFNbeta treatment was able to decrease neuronal apoptosis. Furthermore, the beneficial effects of IFNbeta treatment were reversed when a Stat3 inhibitor was applied. Also an intraperitoneal administration of human recombinant IFNbeta into the systemic compartment was unable to confer the same protective effects as intranasal IFNbeta treatment. PMID- 27683878 TI - Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice. AB - The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS) myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191), results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191null), we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro To determine whether the loss of myelin seen in Zfp191null mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP) is deficient. Interestingly, Mbpshi (shiverer) mice had far fewer transcripts perturbed with the loss of myelin alone. This study demonstrates that the loss of ZFP191 disrupts expression of genes involved in oligodendrocyte maturation and myelination, largely independent from the loss of myelin. Nevertheless, hypomyelination in both mouse mutants results in the perturbation of lipid synthesis pathways, suggesting that oligodendrocytes have a feedback system that allows them to regulate myelin lipid synthesis depending on their myelinating state. The data presented are of potential clinical relevance as the human orthologs of the Zfp191 and MBP genes reside on a region of Chromosome 18 that is deleted in childhood leukodystrophies. PMID- 27683879 TI - Enhanced Histochemical Detection of Iron in Paraffin Sections of Mouse Central Nervous System Tissue: Application in the APP/PS1 Mouse Model of Alzheimer's Disease. AB - Histochemical methods of detecting iron in the rodent brain result mainly in the labeling of oligodendrocytes, but as all cells utilize iron, this observation suggests that much of the iron in the central nervous system goes undetected. Paraffin embedding of tissue is a standard procedure that is used to prepare sections for microscopic analysis. In the present study, we questioned whether we could modify the iron histochemical procedure to enable a greater detection of iron in paraffin sections. Indeed, various modifications led to the widespread labeling of iron in mouse brain tissue (for instance, labeling of neurons and neuropil). Sites of focal concentrations, such as cytoplasmic punctate or nucleolar staining, were also observed. The modified procedures were applied to paraffin sections of a mouse model (APP/PS1) of Alzheimer's disease. Iron was revealed in the plaque core and rim. The plaque rim had a fibrillary or granular appearance, and it frequently contained iron-labeled cells. Further analysis indicated that the iron was tightly associated with the core of the plaque, but less so with the rim. In conclusion, modifications to the histochemical staining revealed new insights into the deposition of iron in the central nervous system. In theory, the approach should be transferrable to organs besides the brain and to other species, and the underlying principles should be incorporable into a variety of staining methods. PMID- 27683880 TI - Is diesel equipment in the workplace safe or not? AB - OBJECTIVES: Recently, diesel motor exhaust (DME) has been classified as a known human carcinogen. We used data from epidemiological studies of diesel exposures to perform a quantitative risk assessment to calculate DME exposure levels, expressed as elemental carbon (EC), corresponding to acceptable risk (AR) and maximum tolerable risk (MTR) levels of 4 to 10-5 and 4 to 10-3 for the lifetime excess probability of dying from lung cancer. METHODS: Previously published slope estimates (n=14) of the exposure-response curve (ERC) for EC exposure and lung cancer were used in life-table analyses to calculate EC exposure levels corresponding to the specified AR and MTR levels. RESULTS: Considered ERC slope factors ranged from 0.00060 to 0.0012 natural logarithm of the relative rate (InRR) per MUg/m3 years based on different selections of studies and study specific risk estimates. Exposure limits based on these slope factors were between 0.009-0.017 and 0.85-1.67 MUg/m3 EC for the AR and MTR, respectively. CONCLUSIONS: Derived exposure limits based on the AR and MTR are around or well below 1 MUg/m3 EC. Such limits are below current occupational exposure levels, and in some instances even below environmental exposure levels. Although uncertainties exist in the exact slope factors, these results indicate that an acceptable excess lung cancer mortality risk can only be achieved at very low DME exposure levels, suggesting that diesel engines using older technologies should be removed from the workplace when possible or emissions strictly controlled. PMID- 27683882 TI - The response of the vestibulosympathetic reflex to linear acceleration in the rat. AB - The vestibulosympathetic reflex (VSR) increases blood pressure (BP) upon arising to maintain blood flow to the brain. The optimal directions of VSR activation and whether changes in heart rate (HR) are associated with changes in BP are still not clear. We used manually activated pulses and oscillatory linear accelerations of 0.2-2.5 g along the naso-occipital, interaural, and dorsoventral axes in isoflurane-anesthetized, male Long-Evans rats. BP and HR were recorded with an intra-aortic sensor and acceleration with a three-dimensional accelerometer. Linear regressions of BP changes in accelerations along the upward, downward, and forward axes had slopes of ~3-6 mmHg . g-1 (P < 0.05). Lateral and backward accelerations did not produce consistent changes in BP. Thus upward, downward, and forward translations were the directions that significantly altered BP. HR was unaffected by these translations. The VSR sensitivity to oscillatory forward backward translations was ~6-10 mmHg . g-1 at frequencies of ~0.1 Hz (0.2 g), decreasing to zero at frequencies above 2 Hz (1.8 g). Upward, 70 degrees tilts of an alert rat increased BP by 9 mmHg . g-1 without changes in HR, indicating that anesthesia had not reduced the VSR sensitivity. The similarity in BP induced in alert and anesthetized rats indicates that the VSR is relatively insensitive to levels of alertness and that the VSR is likely to cause changes in BP through modification of peripheral vascular resistance. Thus the VSR, which is directed toward the cardiovascular system, is in contrast to the responses in the alert state that can produce sweating, alterations in BP and HR, and motion sickness. PMID- 27683881 TI - Effects of high-frequency stimulation of the internal pallidal segment on neuronal activity in the thalamus in parkinsonian monkeys. AB - Deep brain stimulation of the internal globus pallidus (GPi) is a major treatment for advanced Parkinson's disease. The effects of this intervention on electrical activity patterns in targets of GPi output, specifically in the thalamus, are poorly understood. The experiments described here examined these effects using electrophysiological recordings in two Rhesus monkeys rendered moderately parkinsonian through treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after sampling control data in the same animals. Analysis of spontaneous spiking activity of neurons in the basal ganglia-receiving areas of the ventral thalamus showed that MPTP-induced parkinsonism is associated with a reduction of firing rates of segments of the data that contained neither bursts nor decelerations, and with increased burst firing. Spectral analyses revealed an increase of power in the 3- to 13-Hz band and a reduction in the gamma-range in the spiking activity of these neurons. Electrical stimulation of the ventrolateral motor territory of GPi with macroelectrodes, mimicking deep brain stimulation in parkinsonian patients (bipolar electrodes, 0.5 mm intercontact distance, biphasic stimuli, 120 Hz, 100 MUs/phase, 200 MUA), had antiparkinsonian effects. The stimulation markedly reduced oscillations in thalamic firing in the 13- to 30-Hz range and uncoupled the spiking activity of recorded neurons from simultaneously recorded local field potential (LFP) activity. These results confirm that oscillatory and nonoscillatory characteristics of spontaneous activity in the basal ganglia receiving ventral thalamus are altered in MPTP induced parkinsonism. Electrical stimulation of GPi did not entrain thalamic activity but changed oscillatory activity in the ventral thalamus and altered the relationship between spikes and simultaneously recorded LFPs. PMID- 27683883 TI - Persistence of reduced neuromotor noise in long-term motor skill learning. AB - It is well documented that variability in motor performance decreases with practice, yet the neural and computational mechanisms that underlie this decline, particularly during long-term practice, are little understood. Decreasing variability is frequently examined in terms of error corrections from one trial to the next. However, the ubiquitous noise from all levels of the sensorimotor system is also a significant contributor to overt variability. While neuromotor noise is typically assumed and modeled as immune to practice, the present study challenged this notion. We investigated the long-term practice of a novel motor skill to test whether neuromotor noise can be attenuated, specifically when aided by reward. Results showed that both reward and self-guided practice over 11 days improved behavior by decreasing noise rather than effective error corrections. When the challenge for obtaining reward increased, subjects reduced noise even further. Importantly, when task demands were relaxed again, this reduced level of noise persisted for 5 days. A stochastic learning model replicated both the attenuation and persistence of noise by scaling the noise amplitude as a function of reward. More insight into variability and intrinsic noise and its malleability has implications for training and rehabilitation interventions. PMID- 27683884 TI - Transmission of auditory sensory information decreases in rate and temporal precision at the endbulb of Held synapse during age-related hearing loss. AB - Age-related hearing loss (ARHL) is largely attributed to structural changes and functional declines in the peripheral auditory system, which include synaptopathy at the inner hair cell/spiral ganglion cell (SGC) connection and the loss of SGCs. However, functional changes at the central terminals of SGCs, namely the auditory nerve synapses in the cochlear nucleus, are not yet fully understood during ARHL. With the use of young (1-3 mo) and old (25-30 mo) CBA/CaJ mice, this study evaluated the intrinsic properties of the bushy neurons postsynaptic to the endbulb of Held synapses, and the firing properties of these neurons to direct current injections as well as to synaptic inputs from the auditory nerve. Results showed that bushy neurons in old mice are more excitable and are able to fire spikes at similar rate and timing to direct current injections as those in young mice. In response to synaptic inputs, however, bushy neurons from old mice fired spikes with significantly decreased rate and reduced temporal precision to stimulus trains at 100 and 400 Hz, with the drop in firing probability more profound at 400 Hz. It suggests that transmission of auditory information at the endbulb is declined in both rate and timing during aging, which signifies the loss of sensory inputs to the central auditory system under ARHL. The study proposes that, in addition to damages at the peripheral terminals of SGCs as well as the loss of SGCs, functional decline at the central terminals of surviving SGCs is also an essential component of ARHL. PMID- 27683885 TI - Neuron-glia cross talk revealed in reverberating networks by simultaneous extracellular recording of spikes and astrocytes' glutamate transporter and K+ currents. AB - Astrocytes uptake synaptically released glutamate with electrogenic transporters (GluT) and buffer the spike-dependent extracellular K+ excess with background K+ channels. We studied neuronal spikes and the slower astrocytic signals on reverberating neocortical cultures and organotypic slices from mouse brains. Spike trains and glial responses were simultaneously captured from individual sites of multielectrode arrays (MEA) by splitting the recorded traces into appropriate filters and reconstructing the original signal by deconvolution. GluT currents were identified by using dl-threo-beta-benzyloxyaspartate (TBOA). K+ currents were blocked by 30 MUM Ba2+, suggesting a major contribution of inwardly rectifying K+ currents. Both types of current were tightly correlated with the spike rate, and their astrocytic origin was tested in primary cultures by blocking glial proliferation with cytosine beta-d-arabinofuranoside (AraC). The spike-related, time-locked inward and outward K+ currents in different regions of the astrocyte syncytium were consistent with the assumptions of the spatial K+ buffering model. In organotypic slices from ventral tegmental area and prefrontal cortex, the GluT current amplitudes exceeded those observed in primary cultures by several orders of magnitude, which allowed to directly measure transporter currents with a single electrode. Simultaneously measuring cell signals displaying widely different amplitudes and kinetics will help clarify the neuron glia interplay and make it possible to follow the cross talk between different cell types in excitable as well as nonexcitable tissue. PMID- 27683887 TI - Neurons as oscillators. AB - Regularly spiking neurons can be described as oscillators. In this article we review some of the insights gained from this conceptualization and their relevance for systems neuroscience. First, we explain how a regularly spiking neuron can be viewed as an oscillator and how the phase-response curve (PRC) describes the response of the neuron's spike times to small perturbations. We then discuss the meaning of the PRC for a single neuron's spiking behavior and review the PRCs measured from a variety of neurons in a range of spiking regimes. Next, we show how the PRC can be related to a number of common measures used to quantify neuronal firing, such as the spike-triggered average and the peristimulus histogram. We further show that the response of a neuron to correlated inputs depends on the shape of the PRC. We then explain how the PRC of single neurons can be used to predict neural network behavior. Given the PRC, conduction delays, and the waveform and time course of the synaptic potentials, it is possible to predict neural population behavior such as synchronization. The PRC also allows us to quantify the robustness of the synchronization to heterogeneity and noise. We finally ask how to combine the measured PRCs and the predictions based on PRC to further the understanding of systems neuroscience. As an example, we discuss how the change of the PRC by the neuromodulator acetylcholine could lead to a destabilization of cortical network dynamics. Although all of these studies are grounded in mathematical abstractions that do not strictly hold in biology, they provide good estimates for the emergence of the brain's network activity from the properties of individual neurons. The study of neurons as oscillators can provide testable hypotheses and mechanistic explanations for systems neuroscience. PMID- 27683886 TI - Learning the trajectory of a moving visual target and evolution of its tracking in the monkey. AB - An object moving in the visual field triggers a saccade that brings its image onto the fovea. It is followed by a combination of slow eye movements and catch up saccades that try to keep the target image on the fovea as long as possible. The accuracy of this ability to track the "here-and-now" location of a visual target contrasts with the spatiotemporally distributed nature of its encoding in the brain. We show in six experimentally naive monkeys how this performance is acquired and gradually evolves during successive daily sessions. During the early exposure, the tracking is mostly saltatory, made of relatively large saccades separated by low eye velocity episodes, demonstrating that accurate (here and now) pursuit is not spontaneous and that gaze direction lags behind its location most of the time. Over the sessions, while the pursuit velocity is enhanced, the gaze is more frequently directed toward the current target location as a consequence of a 25% reduction in the number of catch-up saccades and a 37% reduction in size (for the first saccade). This smoothing is observed at several scales: during the course of single trials, across the set of trials within a session, and over successive sessions. We explain the neurophysiological processes responsible for this combined evolution of saccades and pursuit in the absence of stringent training constraints. More generally, our study shows that the oculomotor system can be used to discover the neural mechanisms underlying the ability to synchronize a motor effector with a dynamic external event. PMID- 27683888 TI - Trial-to-trial adaptation in control of arm reaching and standing posture. AB - Classical theories of motor learning hypothesize that adaptation is driven by sensorimotor error; this is supported by studies of arm and eye movements that have shown that trial-to-trial adaptation increases with error. Studies of postural control have shown that anticipatory postural adjustments increase with the magnitude of a perturbation. However, differences in adaptation have been observed between the two modalities, possibly due to either the inherent instability or sensory uncertainty in standing posture. Therefore, we hypothesized that trial-to-trial adaptation in posture should be driven by error, similar to what is observed in arm reaching, but the nature of the relationship between error and adaptation may differ. Here we investigated trial-to-trial adaptation of arm reaching and postural control concurrently; subjects made reaching movements in a novel dynamic environment of varying strengths, while standing and holding the handle of a force-generating robotic arm. We found that error and adaptation increased with perturbation strength in both arm and posture. Furthermore, in both modalities, adaptation showed a significant correlation with error magnitude. Our results indicate that adaptation scales proportionally with error in the arm and near proportionally in posture. In posture only, adaptation was not sensitive to small error sizes, which were similar in size to errors experienced in unperturbed baseline movements due to inherent variability. This finding may be explained as an effect of uncertainty about the source of small errors. Our findings suggest that in rehabilitation, postural error size should be considered relative to the magnitude of inherent movement variability. PMID- 27683889 TI - Reduced temporal processing in older, normal-hearing listeners evident from electrophysiological responses to shifts in interaural time difference. AB - Previous electrophysiological studies of interaural time difference (ITD) processing have demonstrated that ITDs are represented by a nontopographic population rate code. Rather than narrow tuning to ITDs, neural channels have broad tuning to ITDs in either the left or right auditory hemifield, and the relative activity between the channels determines the perceived lateralization of the sound. With advancing age, spatial perception weakens and poor temporal processing contributes to declining spatial acuity. At present, it is unclear whether age-related temporal processing deficits are due to poor inhibitory controls in the auditory system or degraded neural synchrony at the periphery. Cortical processing of spatial cues based on a hemifield code are susceptible to potential age-related physiological changes. We consider two distinct predictions of age-related changes to ITD sensitivity: declines in inhibitory mechanisms would lead to increased excitation and medial shifts to rate-azimuth functions, whereas a general reduction in neural synchrony would lead to reduced excitation and shallower slopes in the rate-azimuth function. The current study tested these possibilities by measuring an evoked response to ITD shifts in a narrow-band noise. Results were more in line with the latter outcome, both from measured latencies and amplitudes of the global field potentials and source-localized waveforms in the left and right auditory cortices. The measured responses for older listeners also tended to have reduced asymmetric distribution of activity in response to ITD shifts, which is consistent with other sensory and cognitive processing models of aging. PMID- 27683890 TI - Electrosensory processing in Apteronotus albifrons: implications for general and specific neural coding strategies across wave-type weakly electric fish species. AB - Understanding how the brain processes sensory input to generate behavior remains an important problem in neuroscience. Towards this end, it is useful to compare results obtained across multiple species to gain understanding as to the general principles of neural coding. Here we investigated hindbrain pyramidal cell activity in the weakly electric fish Apteronotus albifrons We found strong heterogeneities when looking at baseline activity. Additionally, ON- and OFF-type cells responded to increases and decreases of sinusoidal and noise stimuli, respectively. While both cell types displayed band-pass tuning, OFF-type cells were more broadly tuned than their ON-type counterparts. The observed heterogeneities in baseline activity as well as the greater broadband tuning of OFF-type cells were both similar to those previously reported in other weakly electric fish species, suggesting that they constitute general features of sensory processing. However, we found that peak tuning occurred at frequencies ~15 Hz in A. albifrons, which is much lower than values reported in the closely related species Apteronotus leptorhynchus and the more distantly related species Eigenmannia virescens In response to stimuli with time-varying amplitude (i.e., envelope), ON- and OFF-type cells displayed similar high-pass tuning curves characteristic of fractional differentiation and possibly indicate optimized coding. These tuning curves were qualitatively similar to those of pyramidal cells in the closely related species A. leptorhynchus In conclusion, comparison between our and previous results reveals general and species-specific neural coding strategies. We hypothesize that differences in coding strategies, when observed, result from different stimulus distributions in the natural/social environment. PMID- 27683892 TI - Developmental experience-dependent plasticity in the first synapse of the Drosophila olfactory circuit. AB - Evidence accumulating over the past 15 years soundly refutes the dogma that the Drosophila nervous system is hardwired. The preponderance of studies reveals activity-dependent neural circuit refinement driving optimization of behavioral outputs. We describe developmental, sensory input-dependent plasticity in the brain olfactory antennal lobe, which we term long-term central adaption (LTCA). LTCA is evoked by prolonged exposure to an odorant during the first week of posteclosion life, resulting in a persistently decreased response to aversive odors and an enhanced response to attractive odors. This limited window of early use, experience-dependent plasticity represents a critical period of olfactory circuit refinement tuned by initial sensory input. Consequent behavioral adaptations have been associated with changes in the output of olfactory projection neurons to higher brain centers. Recent studies have indicated a central role for local interneuron signaling in LTCA presentation. Genetic and molecular analyses have implicated the mRNA-binding fragile X mental retardation protein and ataxin-2 regulators, Notch trans-synaptic signaling, and cAMP signal transduction as core regulatory steps driving LTCA. In this article, we discuss the structural, functional, and behavioral changes associated with LTCA and review our current understanding of the molecular pathways underlying these developmental, experience-dependent changes in the olfactory circuitry. PMID- 27683893 TI - Integration of motion energy from overlapping random background noise increases perceived speed of coherently moving stimuli. AB - The perception of visual motion can be profoundly influenced by visual context. To gain insight into how the visual system represents motion speed, we investigated how a background stimulus that did not move in a net direction influenced the perceived speed of a center stimulus. Visual stimuli were two overlapping random-dot patterns. The center stimulus moved coherently in a fixed direction, whereas the background stimulus moved randomly. We found that human subjects perceived the speed of the center stimulus to be significantly faster than its veridical speed when the background contained motion noise. Interestingly, the perceived speed was tuned to the noise level of the background. When the speed of the center stimulus was low, the highest perceived speed was reached when the background had a low level of motion noise. As the center speed increased, the peak perceived speed was reached at a progressively higher background noise level. The effect of speed overestimation required the center stimulus to overlap with the background. Increasing the background size within a certain range enhanced the effect, suggesting spatial integration. The speed overestimation was significantly reduced or abolished when the center stimulus and the background stimulus had different colors, or when they were placed at different depths. When the center- and background-stimuli were perceptually separable, speed overestimation was correlated with perceptual similarity between the center- and background-stimuli. These results suggest that integration of motion energy from random motion noise has a significant impact on speed perception. Our findings put new constraints on models regarding the neural basis of speed perception. PMID- 27683895 TI - Specialized Regulatory T Cells for Optimal Suppression of T Cell Responses in GN. PMID- 27683891 TI - Callosal dysfunction explains injury sequelae in a computational network model of axonal injury. AB - Mild traumatic brain injury (mTBI) often results in neurobehavioral aberrations such as impaired attention and increased reaction time. Diffusion imaging and postmortem analysis studies suggest that mTBI primarily affects myelinated axons in white matter tracts. In particular, corpus callosum, mediating interhemispheric information exchange, has been shown to be affected in mTBI. Yet little is known about the mechanisms linking the injury of myelinated callosal axons to the neurobehavioral sequelae of mTBI. To address this issue, we devised and studied a large, biologically plausible neuronal network model of cortical tissue. Importantly, the model architecture incorporated intra- and interhemispheric organization, including myelinated callosal axons and distance dependent axonal conduction delays. In the resting state, the intact model network exhibited several salient features, including alpha-band (8-12 Hz) collective activity with low-frequency irregular spiking of individual neurons. The network model of callosal injury captured several clinical observations, including 1) "slowing down" of the network rhythms, manifested as an increased resting-state theta-to-alpha power ratio, 2) reduced response to attention-like network stimulation, manifested as a reduced spectral power of collective activity, and 3) increased population response time in response to stimulation. Importantly, these changes were positively correlated with injury severity, supporting proposals to use neurobehavioral indices as biomarkers for determining the severity of injury. Our modeling effort helps to understand the role played by the injury of callosal myelinated axons in defining the neurobehavioral sequelae of mTBI. PMID- 27683894 TI - Visual sensitivity of frontal eye field neurons during the preparation of saccadic eye movements. AB - Primate vision is continuously disrupted by saccadic eye movements, and yet this disruption goes unperceived. One mechanism thought to reduce perception of this self-generated movement is saccadic suppression, a global loss of visual sensitivity just before, during, and after saccadic eye movements. The frontal eye field (FEF) is a candidate source of neural correlates of saccadic suppression previously observed in visual cortex, because it contributes to the generation of visually guided saccades and modulates visual cortical responses. However, whether the FEF exhibits a perisaccadic reduction in visual sensitivity that could be transmitted to visual cortex is unknown. To determine whether the FEF exhibits a signature of saccadic suppression, we recorded the visual responses of FEF neurons to brief, full-field visual probe stimuli presented during fixation and before onset of saccades directed away from the receptive field in rhesus macaques (Macaca mulatta) We measured visual sensitivity during both epochs and found that it declines before saccade onset. Visual sensitivity was significantly reduced in visual but not visuomotor neurons. This reduced sensitivity was also present in visual neurons with no movement-related modulation during visually guided saccades and thus occurred independently from movement-related activity. Across the population of visual neurons, sensitivity began declining ~80 ms before saccade onset. We also observed a similar presaccadic reduction in sensitivity to isoluminant, chromatic stimuli. Our results demonstrate that the signaling of visual information by FEF neurons is reduced during saccade preparation, and thus these neurons exhibit a signature of saccadic suppression. PMID- 27683896 TI - Genetically Encoded Voltage Indicators: Opportunities and Challenges. AB - A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. SIGNIFICANCE STATEMENT: Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions. PMID- 27683897 TI - Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter. AB - The impact of aging on CNS white matter (WM) is of general interest because the global effects of aging on myelinated nerve fibers are more complex and profound than those in cortical gray matter. It is important to distinguish between axonal changes created by normal aging and those caused by neurodegenerative diseases, including multiple sclerosis, stroke, glaucoma, Alzheimer's disease, and traumatic brain injury. Using three-dimensional electron microscopy, we show that in mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicker myelin, and are characterized by longer and thicker mitochondria, which are associated with altered levels of mitochondrial shaping proteins. These structural alterations in aging mitochondria correlate with lower ATP levels and increased generation of nitric oxide, protein nitration, and lipid peroxidation. Moreover, mitochondria-smooth endoplasmic reticulum interactions are compromised due to decreased associations and decreased levels of calnexin and calreticulin, suggesting a disruption in Ca(2+) homeostasis and defective unfolded protein responses in aging axons. Despite these age-related modifications, axon function is sustained in aging WM, which suggests that age dependent changes do not lead to irreversible functional decline under normal conditions, as is observed in neurodegenerative diseases. SIGNIFICANCE STATEMENT: Aging is a common risk factor for a number of neurodegenerative diseases, including stroke. Mitochondrial dysfunction and oxidative damage with age are hypothesized to increase risk for stroke. We compared axon-myelin-node mitochondrion-smooth endoplasmic reticulum (SER) interactions in white matter obtained at 1 and 12 months. We show that aging axons have enlarged volume, thicker myelin, and elongated and thicker mitochondria. Furthermore, there are reduced SER connections to mitochondria that correlate with lower calnexin and calreticulin levels. Despite a prominent decrease in number, elongated aging mitochondria produce excessive stress markers with reduced ATP production. Because axons maintain function under these conditions, our study suggests that it is important to understand the process of normal brain aging to identify neurodegenerative changes. PMID- 27683898 TI - Neural Signatures of Value Comparison in Human Cingulate Cortex during Decisions Requiring an Effort-Reward Trade-off. AB - Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT: The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization. PMID- 27683900 TI - Shared Neural Mechanisms for the Evaluation of Intense Sensory Stimulation and Economic Reward, Dependent on Stimulation-Seeking Behavior. AB - Why are some people strongly motivated by intense sensory experiences? Here we investigated how people encode the value of an intense sensory experience compared with economic reward, and how this varies according to stimulation seeking preference. Specifically, we used a novel behavioral task in combination with computational modeling to derive the value individuals assigned to the opportunity to experience an intense tactile stimulus (mild electric shock). We then examined functional imaging data recorded during task performance to see how the opportunity to experience the sensory stimulus was encoded in stimulation seekers versus stimulation-avoiders. We found that for individuals who positively sought out this kind of sensory stimulation, there was common encoding of anticipated economic and sensory rewards in the ventromedial prefrontal cortex. Conversely, there was robust encoding of the modeled probability of receiving such stimulation in the insula only in stimulation-avoidant individuals. Finally, we found preliminary evidence that sensory prediction error signals may be positively signed for stimulation-seekers, but negatively signed for stimulation avoiders, in the posterior cingulate cortex. These findings may help explain why high intensity sensory experiences are appetitive for some individuals, but not for others, and may have relevance for the increased vulnerability for some psychopathologies, but perhaps increased resilience for others, in high sensation seeking individuals. SIGNIFICANCE STATEMENT: People vary in their preference for intense sensory experiences. Here, we investigated how different individuals evaluate the prospect of an unusual sensory experience (electric shock), compared with the opportunity to gain a more traditional reward (money). We found that in a subset of individuals who sought out such unusual sensory stimulation, anticipation of the sensory outcome was encoded in the same way as that of monetary gain, in the ventromedial prefrontal cortex. Further understanding of stimulation-seeking behavior may shed light on the etiology of psychopathologies such as addiction, for which high or low sensation-seeking personality has been identified as a risk factor. PMID- 27683902 TI - Field Potential Oscillations in the Bed Nucleus of the Stria Terminalis Correlate with Compulsion in a Rat Model of Obsessive-Compulsive Disorder. AB - The bed nucleus of the stria terminalis (BNST) is implicated in anxiety and reward processing, both of which are associated with obsessive-compulsive disorder (OCD). Specific neuronal groups in the BNST related to anxiety and reward have been identified, but quantitative data about the information carried by local field potential (LFP) signals in this area during obsession/compulsion are lacking. Here we investigate the BNST LFP in the schedule-induced polydipsia, an animal model of OCD. We implanted electrodes bilaterally in the BNST and random control brain regions in 32 male Wistar rats, and recorded corresponding LFP during compulsive and noncompulsive behavior. We first applied high-frequency (100 Hz) electrical stimulation through the implanted electrodes and analyzed its effects on compulsive behavior. We then performed time-frequency analysis of LFPs and statistically compared the normalized power of delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and lower gamma (30-45 Hz) bands between different groups. Our data showed that the normalized delta, beta, and gamma powers in the right BNST were specifically correlated with compulsive behaviors. delta and gamma oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas beta increased after compulsion stopped. Moreover, the effect of BNST electrical stimulation, in terms of suppression of compulsion, was significantly correlated with the percentage change of these bands during compulsion. Our research reveals potential biomarkers and underlying neurophysiological mechanisms of compulsion and warrants further assessment of the use of LFP for closed-loop neuromodulation in OCD. SIGNIFICANCE STATEMENT: Although specific neuronal groups in the bed nucleus of the stria terminalis (BNST) related to anxiety and reward circuitries have been identified, psychopathological information carried by local field potentials in the BNST has not yet been described. We discovered that normalized powers of the right BNST delta, beta, and gamma oscillations were highly correlated with compulsion. Specifically, delta and gamma oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas beta increased after compulsion stopped. Such correlations were not found in other parts of the brain during compulsion, or in the BNST during noncompulsive behavior. Current findings reveal real-time neurophysiological biomarkers of compulsion and warrant further assessment of the use of local field potentials for closed-loop neuromodulation for OCD. PMID- 27683899 TI - Partial Adaptation of Obtained and Observed Value Signals Preserves Information about Gains and Losses. AB - Given that the range of rewarding and punishing outcomes of actions is large but neural coding capacity is limited, efficient processing of outcomes by the brain is necessary. One mechanism to increase efficiency is to rescale neural output to the range of outcomes expected in the current context, and process only experienced deviations from this expectation. However, this mechanism comes at the cost of not being able to discriminate between unexpectedly low losses when times are bad versus unexpectedly high gains when times are good. Thus, too much adaptation would result in disregarding information about the nature and absolute magnitude of outcomes, preventing learning about the longer-term value structure of the environment. Here we investigate the degree of adaptation in outcome coding brain regions in humans, for directly experienced outcomes and observed outcomes. We scanned participants while they performed a social learning task in gain and loss blocks. Multivariate pattern analysis showed two distinct networks of brain regions adapt to the most likely outcomes within a block. Frontostriatal areas adapted to directly experienced outcomes, whereas lateral frontal and temporoparietal regions adapted to observed social outcomes. Critically, in both cases, adaptation was incomplete and information about whether the outcomes arose in a gain block or a loss block was retained. Univariate analysis confirmed incomplete adaptive coding in these regions but also detected nonadapting outcome signals. Thus, although neural areas rescale their responses to outcomes for efficient coding, they adapt incompletely and keep track of the longer-term incentives available in the environment. SIGNIFICANCE STATEMENT: Optimal value based choice requires that the brain precisely and efficiently represents positive and negative outcomes. One way to increase efficiency is to adapt responding to the most likely outcomes in a given context. However, too strong adaptation would result in loss of precise representation (e.g., when the avoidance of a loss in a loss-context is coded the same as receipt of a gain in a gain-context). We investigated an intermediate form of adaptation that is efficient while maintaining information about received gains and avoided losses. We found that frontostriatal areas adapted to directly experienced outcomes, whereas lateral frontal and temporoparietal regions adapted to observed social outcomes. Importantly, adaptation was intermediate, in line with influential models of reference dependence in behavioral economics. PMID- 27683901 TI - A Critical Period in Purkinje Cell Development Is Mediated by Local Estradiol Synthesis, Disrupted by Inflammation, and Has Enduring Consequences Only for Males. AB - Identifying and understanding critical periods in brain development is essential to decoding the long-term impact of widespread, poorly defined, and frequently occurring insults such as inflammation. Using the laboratory rat Rattus norvegicus, we have discovered a narrowly constrained critical period in Purkinje neuron development subject to dysregulation by inflammation. The onset and offset of heightened vulnerability are attributed to a tightly orchestrated gene expression profile present only during the second postnatal week and not the first or third weeks. Genes expressed during this time code for enzymes and receptors which are critical not only for prostaglandin production and activity but also for estradiol production via the aromatase enzyme and estradiol action via the alpha isoform of the estrogen receptor. The two synthetic pathways are connected by prostaglandin E2 (PGE2) activation of the aromatase enzyme, as we reported previously (Dean et al., 2012b) and confirm here. Dysregulation of the PGE2-estradiol pathway during the second week by treatment with PGE2 or lipopolysaccharides produces enduring consequences as a result of reduced growth of Purkinje dendritic trees and impaired juvenile social play behavior, but only in males. The deleterious consequences of inflammation locally in the cerebellum are prevented by peripheral treatment with the cyclooxygenase inhibitor nimesulide or the aromatase inhibitor formestane. These findings highlight a novel regulatory pathway that creates a critical period in brain development vulnerable to dysregulation by inflammation. SIGNIFICANCE STATEMENT: The cerebellum is increasingly appreciated for its role in social, emotional, and cognitive behaviors. It is consistently and severely affected in neuropsychiatric disorders originating during development, such as autism spectrum disorder and schizophrenia. We have identified a critical period in rat development during the second week of life that is dysregulated by inflammatory insults. An intrinsic program of gene expression determines the critical period. The enduring consequences of inflammation during the second postnatal week are stunted dendrites of the cerebellum's principal neurons, Purkinje cells, and impairments in later social behavior. These changes are not evident if inflammation occurs during the first or third week, highlighting the importance of fine-grained analyses of developmental processes and the factors that influence them. PMID- 27683903 TI - Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span. AB - Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. SIGNIFICANCE STATEMENT: Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However, it remains unclear whether this flexibly functional reconfiguration is intrinsic and occurs in the absence of an overt task. In this study, we propose a probabilistic framework to quantify the functional flexibility of each brain region using resting-state fMRI. We identify regions showing high flexibility mainly in the higher-order association cortex. In contrast, primary and unimodal visual and sensory areas show low flexibility. On the other hand, our findings reveal dissociable changes of frontal and parietal cortices in terms of inherent functional flexibility over the life span. PMID- 27683905 TI - Multivariate Pattern Analysis Reveals Category-Related Organization of Semantic Representations in Anterior Temporal Cortex. AB - The neural substrates of semantic representation have been the subject of much controversy. The study of semantic representations is complicated by difficulty in disentangling perceptual and semantic influences on neural activity, as well as in identifying stimulus-driven, "bottom-up" semantic selectivity unconfounded by top-down task-related modulations. To address these challenges, we trained human subjects to associate pseudowords (TPWs) with various animal and tool categories. To decode semantic representations of these TPWs, we used multivariate pattern classification of fMRI data acquired while subjects performed a semantic oddball detection task. Crucially, the classifier was trained and tested on disjoint sets of TPWs, so that the classifier had to use the semantic information from the training set to correctly classify the test set. Animal and tool TPWs were successfully decoded based on fMRI activity in spatially distinct subregions of the left medial anterior temporal lobe (LATL). In addition, tools (but not animals) were successfully decoded from activity in the left inferior parietal lobule. The tool-selective LATL subregion showed greater functional connectivity with left inferior parietal lobule and ventral premotor cortex, indicating that each LATL subregion exhibits distinct patterns of connectivity. Our findings demonstrate category-selective organization of semantic representations in LATL into spatially distinct subregions, continuing the lateral-medial segregation of activation in posterior temporal cortex previously observed in response to images of animals and tools, respectively. Together, our results provide evidence for segregation of processing hierarchies for different classes of objects and the existence of multiple, category-specific semantic networks in the brain. SIGNIFICANCE STATEMENT: The location and specificity of semantic representations in the brain are still widely debated. We trained human participants to associate specific pseudowords with various animal and tool categories, and used multivariate pattern classification of fMRI data to decode the semantic representations of the trained pseudowords. We found that: (1) animal and tool information was organized in category-selective subregions of medial left anterior temporal lobe (LATL); (2) tools, but not animals, were encoded in left inferior parietal lobe; and (3) LATL subregions exhibited distinct patterns of functional connectivity with category-related regions across cortex. Our findings suggest that semantic knowledge in LATL is organized in category-related subregions, providing evidence for the existence of multiple, category-specific semantic representations in the brain. PMID- 27683904 TI - Kinetics of Inhibitory Feedback from Horizontal Cells to Photoreceptors: Implications for an Ephaptic Mechanism. AB - Inhibitory feedback from horizontal cells (HCs) to cones generates center surround receptive fields and color opponency in the retina. Mechanisms of HC feedback remain unsettled, but one hypothesis proposes that an ephaptic mechanism may alter the extracellular electrical field surrounding photoreceptor synaptic terminals, thereby altering Ca(2+) channel activity and photoreceptor output. An ephaptic voltage change produced by current flowing through open channels in the HC membrane should occur with no delay. To test for this mechanism, we measured kinetics of inhibitory feedback currents in Ambystoma tigrinum cones and rods evoked by hyperpolarizing steps applied to synaptically coupled HCs. Hyperpolarizing HCs stimulated inward feedback currents in cones that averaged 8 9 pA and exhibited a biexponential time course with time constants averaging 14 17 ms and 120-220 ms. Measurement of feedback-current kinetics was limited by three factors: (1) HC voltage-clamp speed, (2) cone voltage-clamp speed, and (3) kinetics of Ca(2+) channel activation or deactivation in the photoreceptor terminal. These factors totaled ~4-5 ms in cones meaning that the true fast time constants for HC-to-cone feedback currents were 9-13 ms, slower than expected for ephaptic voltage changes. We also compared speed of feedback to feedforward glutamate release measured at the same cone/HC synapses and found a latency for feedback of 11-14 ms. Inhibitory feedback from HCs to rods was also significantly slower than either measurement kinetics or feedforward release. The finding that inhibitory feedback from HCs to photoreceptors involves a significant delay indicates that it is not due to previously proposed ephaptic mechanisms. SIGNIFICANCE STATEMENT: Lateral inhibitory feedback from horizontal cells (HCs) to photoreceptors creates center-surround receptive fields and color-opponent interactions. Although underlying mechanisms remain unsettled, a longstanding hypothesis proposes that feedback is due to ephaptic voltage changes that regulate photoreceptor synaptic output by altering Ca(2+) channel activity. Ephaptic processes should occur with no delay. We measured kinetics of inhibitory feedback currents evoked in photoreceptors with voltage steps applied to synaptically coupled HCs and found that feedback is too slow to be explained by ephaptic voltage changes generated by current flowing through continuously open channels in HC membranes. By eliminating the proposed ephaptic mechanism for HC feedback regulation of photoreceptor Ca(2+) channels, our data support earlier proposals that synaptic cleft pH changes are more likely responsible. PMID- 27683906 TI - Hypocretin/Orexin Peptides Alter Spike Encoding by Serotonergic Dorsal Raphe Neurons through Two Distinct Mechanisms That Increase the Late Afterhyperpolarization. AB - Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons. Intracellular phospholipase C inhibition (U73122) blocked the entire oeAHP, but neither component was sensitive to PKC inhibition or altered PKA signaling, unlike classical sAHPs. The enhanced SK current did not depend on IP3 mediated Ca(2+) release but resulted from A-current inhibition and the resultant spike broadening, which increased Ca(2+) influx and Ca(2+)-induced-Ca(2+) release, whereas the slower component was insensitive to these factors. Functionally, the oeAHP slowed and stabilized orexin-induced firing compared with firing produced by a virtual orexin conductance lacking the oeAHP. The oeAHP also reduced steady-state firing rate and firing fidelity in response to stimulation, without affecting the initial rate or fidelity. Collectively, these findings reveal a new orexin action in serotonergic raphe neurons and suggest that, when orexin is released during arousal and reward, it enhances the spike encoding of phasic over tonic inputs, such as those related to sensory, motor, and reward events. SIGNIFICANCE STATEMENT: Orexin peptides are known to excite neurons via slow postsynaptic depolarizations. Here we elucidate a significant new orexin action that increases and prolongs the postspike afterhyperpolarization (AHP) in 5-HT dorsal raphe neurons and other arousal-system neurons. Our mechanistic studies establish involvement of two distinct Ca(2+)-dependent AHP currents dependent on phospholipase C signaling but independent of IP3 or PKC. Our functional studies establish that this action preserves responsiveness to phasic inputs while attenuating responsiveness to tonic inputs. Thus, our findings bring new insight into the actions of an important neuropeptide and indicate that, in addition to producing excitation, orexins can tune postsynaptic excitability to better encode the phasic sensory, motor, and reward signals expected during aroused states. PMID- 27683907 TI - The Neurotrophic Factor Receptor p75 in the Rat Dorsolateral Striatum Drives Excessive Alcohol Drinking. AB - Brain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) keeps alcohol intake in moderation. For example, activation of the BDNF receptor tropomyosin receptor kinase B (TrkB) in the DLS reduces intake in rats that consume moderate amounts of alcohol. Here, we tested whether long-term excessive consumption of alcohol produces neuroadaptations in BDNF signaling in the rat DLS. We found that BDNF was no longer able to gate alcohol self administration after a history of repeated cycles of binge alcohol drinking and withdrawal. We then elucidated the possible neuroadaptations that could block the ability of BDNF to keep consumption of alcohol in moderation. We report that intermittent access to 20% alcohol in a two-bottle choice paradigm that models excessive alcohol drinking produces a mobilization of DLS p75 neurotrophin receptor (p75NTR), whose activities oppose those of the Trk receptors, including TrkB. These neuroadaptations were not observed in the DLS of rats exposed to continuous access to 10% alcohol or in rats consuming sucrose. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of the p75NTR gene in the DLS, as well as intra-DLS infusion or systemic administration of the p75NTR modulator, LM11A-31, significantly reduced binge drinking of alcohol. Together, our results suggest that excessive alcohol consumption produces a change in BDNF signaling in the DLS, which is mediated by the recruitment of p75NTR. Our data also imply that modulators of p75NTR signaling could be developed as medications for alcohol abuse disorders. SIGNIFICANCE STATEMENT: Neuroadaptations gate or drive excessive, compulsive alcohol drinking. We previously showed that brain-derived neurotrophic factor and its receptor, TrkB, in the dorsolateral striatum (DLS), are part of an endogenous system that keeps alcohol drinking in moderation. Here, we show that a history of excessive alcohol intake produces neuroadaptations in the DLS that preclude BDNF's ability to gate alcohol self-administration in rats by the recruitment of the low-affinity neurotrophin receptor, p75NTR, whose activities opposes those of the Trk receptors. Finally, we show that the administration of the p75NTR modulator, LM11A-31, significantly reduces excessive alcohol intake suggesting that the drug may be developed as a new treatment for alcohol abuse disorders. PMID- 27683908 TI - Inhibition of YAP/TAZ Activity in Spinal Cord Suppresses Neuropathic Pain. AB - Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development. Signaling of the representative activated molecule Wnt thus becomes a trigger for the development of neuropathic pain and is a potential therapeutic target. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the beta-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status in rats. Peripheral nerve injury causes rapid-onset and long-lasting nuclear accumulation of YAP/TAZ/beta-catenin in the spinal dorsal horn. Spinal inhibition or knock down of either YAP or TAZ suppresses mechanical allodynia induced by nerve injury or the pain initiators lysophosphatidic acid and Wnt3a. Promoting the nuclear accumulation of YAP/TAZ leads to mechanical hypersensitivity in naive animals. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/beta catenin and can greatly suppress neuropathic pain and the associated neurochemical alterations. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening for potent analgesics for the treatment of neuropathic pain. SIGNIFICANCE STATEMENT: Mechanisms that underlie neuropathic pain remain elusive. We have demonstrated recently that nerve injury can activate Wnt signaling, which becomes a trigger for the development of neuropathic pain. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the beta-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/beta-catenin and can greatly suppress neuropathic pain. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening of potent analgesics for the treatment of neuropathic pain. PMID- 27683910 TI - Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear. AB - The amygdala serves as emotional center to mediate innate fear behaviors that are reflected through neuronal responses to environmental aversive cues. However, the molecular mechanism underlying the initial neuron responses is poorly understood. In this study, we monitored the innate defensive responses to aversive stimuli of either elevated plus maze or predator odor in juvenile mice and found that glutamatergic neurons were activated in amygdala. Loss of EphB2, a receptor tyrosine kinase expressed in amygdala neurons, suppressed the reactions and led to defects in spine morphogenesis and fear behaviors. We further found a coupling of spinogenesis with these threat cues induced neuron activation in developing amygdala that was controlled by EphB2. A constitutively active form of EphB2 was sufficient to rescue the behavioral and morphological defects caused by ablation of ephrin-B3, a brain-enriched ligand to EphB2. These data suggest that kinase dependent EphB2 intracellular signaling plays a major role for innate fear responses during the critical developing period, in which spinogenesis in amygdala glutamatergic neurons was involved. SIGNIFICANCE STATEMENT: Generation of innate fear responses to threat as an evolutionally conserved brain feature relies on development of functional neural circuit in amygdala, but the molecular mechanism remains largely unknown. We here identify that EphB2 receptor tyrosine kinase, which is specifically expressed in glutamatergic neurons, is required for the innate fear responses in the neonatal brain. We further reveal that EphB2 mediates coordination of spinogenesis and neuron activation in amygdala during the critical period for the innate fear. EphB2 catalytic activity plays a major role for the behavior upon EphB-ephrin-B3 binding and transnucleus neuronal connections. Our work thus indicates an essential synaptic molecular signaling within amygdala that controls synapse development and helps bring about innate fear emotions in the postnatal developing brain. PMID- 27683909 TI - Genetic Restoration of Plasma ApoE Improves Cognition and Partially Restores Synaptic Defects in ApoE-Deficient Mice. AB - Alzheimer's disease (AD) is the most common form of dementia in individuals over the age of 65 years. The most prevalent genetic risk factor for AD is the epsilon4 allele of apolipoprotein E (ApoE4), and novel AD treatments that target ApoE are being considered. One unresolved question in ApoE biology is whether ApoE is necessary for healthy brain function. ApoE knock-out (KO) mice have synaptic loss and cognitive dysfunction; however, these findings are complicated by the fact that ApoE knock-out mice have highly elevated plasma lipid levels, which may independently affect brain function. To bypass the effect of ApoE loss on plasma lipids, we generated a novel mouse model that expresses ApoE normally in peripheral tissues, but has severely reduced ApoE in the brain, allowing us to study brain ApoE loss in the context of a normal plasma lipid profile. We found that these brain ApoE knock-out (bEKO) mice had synaptic loss and dysfunction similar to that of ApoE KO mice; however, the bEKO mice did not have the learning and memory impairment observed in ApoE KO mice. Moreover, we found that the memory deficit in the ApoE KO mice was specific to female mice and was fully rescued in female bEKO mice. Furthermore, while the AMPA/NMDA ratio was reduced in ApoE KO mice, it was unchanged in bEKO mice compared with controls. These findings suggest that plasma lipid levels can influence cognition and synaptic function independent of ApoE expression in the brain. SIGNIFICANCE STATEMENT: One proposed treatment strategy for Alzheimer's disease (AD) is the reduction of ApoE, whose epsilon4 isoform is the most common genetic risk factor for the disease. A major concern of this strategy is that an animal model of ApoE deficiency, the ApoE knock-out (KO) mouse, has reduced synapses and cognitive impairment; however, these mice also develop dyslipidemia and severe atherosclerosis. Here, we have shown that genetic restoration of plasma ApoE to wild-type levels normalizes plasma lipids in ApoE KO mice. While this does not rescue synaptic loss, it does completely restore learning and memory in the mice, suggesting that both CNS and plasma ApoE are independent parameters that affect brain health. PMID- 27683913 TI - Putative Cell Adhesion Membrane Protein Vstm5 Regulates Neuronal Morphology and Migration in the Central Nervous System. AB - During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporation in utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics. SIGNIFICANCE STATEMENT: Neuronal migration and morphogenesis play critical roles in brain development and function. In this study, we demonstrate for the first time that V-set and transmembrane domain-containing protein 5 (Vstm5), a putative cell adhesion membrane protein, modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Vstm5 is also one of the target genes responsible for variations in patient responses to treatments for major depressive disorder. Our results provide the first evidence that Vstm5 is a novel factor involved in the modulation of the neuronal membrane and a critical element in normal neural circuit formation during mammalian brain development. PMID- 27683912 TI - Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking. AB - The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues. SIGNIFICANCE STATEMENT: The ventromedial prefrontal cortex (vmPFC) projection to the nucleus accumbens shell is important for extinction of cocaine seeking, but its anatomical proximity to the relapse promoting projection from the dorsomedial prefrontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activity in one pathway or the other using traditional pharmacotherapy (e.g., systemically administered drugs). Viral-mediated gene delivery of an activating Gq-DREADD to vmPFC and/or vmPFC projections to the nucleus accumbens shell allows the chemogenetic exploitation of this extinction neural circuit to reduce cocaine seeking and was particularly effective against relapse triggered by cocaine reminder cues. PMID- 27683914 TI - Transfer after Dual n-Back Training Depends on Striatal Activation Change. AB - The dual n-back working memory (WM) training paradigm (comprising auditory and visual stimuli) has gained much attention since studies have shown widespread transfer effects. By including a multimodal dual-task component, the task is demanding to the human cognitive system. We investigated whether dual n-back training improves general cognitive resources or a task-specific WM updating process in participants. We expected: (1) widespread transfer effects and the recruitment of a common neuronal network by the training and the transfer tasks and (2) narrower transfer results and that a common activation network alone would not produce transfer, but instead an activation focus on the striatum, which is associated with WM updating processes. The training group showed transfer to an untrained dual-modality WM updating task, but not to single-task versions of the training or the transfer task. They also showed diminished neuronal overlap between the training and the transfer task from pretest to posttest and an increase in striatal activation in both tasks. Furthermore, we found an association between the striatal activation increase and behavioral improvement. The control groups showed no transfer and no change in the amount of activation overlap or in striatal activation from pretest to posttest. We conclude that, instead of improving general cognitive resources (which would have required a transfer effect to all transfer tasks and that a frontal activation overlap between the tasks produced transfer), dual n-back training improved a task-specific process: WM updating of stimuli from two modalities. SIGNIFICANCE STATEMENT: The current study allows for a better understanding of the cognitive and neural effects of working memory (WM) training and transfer. It shows that dual n-back training mainly improves specific processes of WM updating, and this improvement leads to narrow transfer effects to tasks involving the same processes. On a neuronal level this is accompanied by increased neural activation in the striatum that is related to WM updating. The current findings challenge the view that dual n-back training provokes a general boosting of the WM system and of its neural underpinnings located in frontoparietal brain regions. Instead, the findings imply the relevance of task-specific brain regions which are involved in important cognitive processes during training and transfer tasks. PMID- 27683911 TI - Impact of Sex and Menopausal Status on Episodic Memory Circuitry in Early Midlife. AB - Cognitive neuroscience of aging studies traditionally target participants age 65 and older. However, epidemiological surveys show that many women report increased forgetfulness earlier in the aging process, as they transition to menopause. In this population-based fMRI study, we stepped back by over a decade to characterize the changes in memory circuitry that occur in early midlife, as a function of sex and women's reproductive stage. Participants (N = 200; age range, 45-55) performed a verbal encoding task during fMRI scanning. Reproductive histories and serologic evaluations were used to determine menopausal status. Results revealed a pronounced impact of reproductive stage on task-evoked hippocampal responses, despite minimal difference in chronological age. Next, we examined the impact of sex and reproductive stage on functional connectivity across task-related brain regions. Postmenopausal women showed enhanced bilateral hippocampal connectivity relative to premenopausal and perimenopausal women. Across women, lower 17beta-estradiol concentrations were related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task, strongly implicating sex steroids in the regulation of this circuitry. Finally, subgroup analyses revealed that high performing postmenopausal women (relative to low and middle performers) exhibited a pattern of brain activity akin to premenopausal women. Together, these findings underscore the importance of considering reproductive stage, not simply chronological age, to identify neuronal and cognitive changes that unfold in the middle decades of life. In keeping with preclinical studies, these human findings suggest that the decline in ovarian estradiol production during menopause plays a significant role in shaping memory circuitry. SIGNIFICANCE STATEMENT: Maintaining intact memory function with age is one of the greatest public health challenges of our time, and women have an increased risk for memory disorders relative to men later in life. We studied adults early in the aging process, as women transition into menopause, to identify neuronal and cognitive changes that unfold in the middle decades of life. Results demonstrate regional and network-level differences in memory encoding-related activity as a function of women's reproductive stage, independent of chronological age. Analyzing data without regard to sex or menopausal status obscured group differences in circuit-level neural strategies associated with successful memory retrieval. These findings suggest that early changes in memory circuitry are evident decades before the age range traditionally targeted by cognitive neuroscience of aging studies. PMID- 27683917 TI - Active immunotherapy may delay disability in progressive MS. PMID- 27683915 TI - Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus. AB - Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. SIGNIFICANCE STATEMENT: Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at the level of the lateral lemniscus, and to long-lasting presynaptic and postsynaptic structural and molecular effects at the endbulb of the Held synapse. Knowledge of the structural and molecular changes associated with decreased sensory experience, along with their potential reversibility, is important for the treatment of hearing deficits, such as hyperacusis and chronic otitis media with effusion, which is prevalent in young children with language acquisition or educational disabilities. PMID- 27683916 TI - Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis. AB - OBJECTIVE: To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy. METHODS: The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted. RESULTS: For the EDSS 3-6, 4-6 and 6-6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92-1.11) and postbaseline (2.15-2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58-3.07; p<0.001). A greater proportion of each epoch treated with higher efficacy therapies was associated with lower risk of reaching the outcome disability step (HRs 0.72-0.91 per 25%; p<=0.02). 3 sensitivity analyses confirmed these results. CONCLUSIONS: Disease progression during moderately advanced and advanced MS is highly variable and amnesic to prior disease activity. Lower relapse rates and greater time on higher efficacy immunomodulatory therapy after reaching EDSS steps 3, 4 and 6 are associated with a decreased risk of accumulating further disability. Highly effective immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced relapse-onset MS. PMID- 27683918 TI - Clinical features of functional (psychogenic) eye movement disorders. PMID- 27683919 TI - Too fast: rare neuropathic pain state associated with easy activation of NaV1.9. PMID- 27683946 TI - Quantum Scattering Calculations of Transport Properties for the H-N2 and H-CH4 Collision Pairs. AB - Transport properties for collisions of hydrogen atoms with molecular nitrogen and methane were calculated through close-coupling quantum scattering calculations. For these calculations, potential energy surfaces for the interaction of H atoms with these molecules, with their geometries fixed at the respective equilibrium structures, were obtained with a coupled cluster method that included single, double, and (perturbatively) triple excitations [RCCSD(T)]. The computed transport properties for H-N2 were found to be similar in magnitude to those computed in a previous study but significantly different from those obtained through the conventional approach that employs isotropic Lennard-Jones (LJ) (12 6) potentials. The differences in the transport properties for H-CH4 computed in this work and those estimated with isotropic LJ potentials are somewhat smaller. PMID- 27683920 TI - Selective subcortical contributions to gait impairments in males with the FMR1 premutation. PMID- 27683947 TI - Stranski-Krastanov and Volmer-Weber CVD Growth Regimes To Control the Stacking Order in Bilayer Graphene. AB - Aside from unusual properties of monolayer graphene, bilayer has been shown to have even more interesting physics, in particular allowing bandgap opening with dual gating for proper interlayer symmetry. Such properties, promising for device applications, ignited significant interest in understanding and controlling the growth of bilayer graphene. Here we systematically investigate a broad set of flow rates and relative gas ratio of CH4 to H2 in atmospheric pressure chemical vapor deposition of multilayered graphene. Two very different growth windows are identified. For relatively high CH4 to H2 ratios, graphene growth is relatively rapid with an initial first full layer forming in seconds upon which new graphene flakes nucleate then grow on top of the first layer. The stacking of these flakes versus the initial graphene layer is mostly turbostratic. This growth mode can be likened to Stranski-Krastanov growth. With relatively low CH4 to H2 ratios, growth rates are reduced due to a lower carbon supply rate. In addition bi-, tri , and few-layer flakes form directly over the Cu substrate as individual islands. Etching studies show that in this growth mode subsequent layers form beneath the first layer presumably through carbon radical intercalation. This growth mode is similar to that found with Volmer-Weber growth and was shown to produce highly oriented AB-stacked materials. These systematic studies provide new insight into bilayer graphene formation and define the synthetic range where gapped bilayer graphene can be reliably produced. PMID- 27683949 TI - Depression and anxiety were low amongst virally suppressed, long-term treated HIV infected individuals enrolled in a public sector antiretroviral program in Thailand. AB - HIV/AIDS and anxiety/depression are interlinked. HIV-infected patients suffering from depression may be at risk for poor adherence which may contribute to HIV disease progression. Additionally, an HIV diagnosis and/or using certain antiretroviral agents may trigger symptoms of anxiety/depression. The objective of the study was to assess the prevalence and factors associated with anxiety and depression in HIV-infected patients from the Thai National HIV Treatment Program. This cross-sectional study was performed from January 2012 to December 2012 in HIV-infected out-patients, aged >=18 years, from three HIV referral centers. Symptoms of anxiety and depression were measured using the Thai-validated Hospital Anxiety and Depression Scale (HADS). A score of >=11 was defined as having anxiety and depression. Associated factors were assessed by multivariate logistic regression. Totally 2023 (56% males) patients were enrolled. All patients received antiretroviral therapy (ART) for a mean duration of 7.7 years. Median CD4 was 495 cells/mm3. Ninety-five percent had HIV-RNA < 50 copies/ml. Thirty-three percent were currently on efavirenz (EFV)-based ART. The prevalence of anxiety and depression were 4.8% and 3.1%, respectively. About 1.3% had both anxiety and depression. In multivariate logistic models, the female sex [OR = 1.6(95%CI 1.1-2.3), p = .01], having adherence <90% [OR = 2.2(95%CI 1.5-3.4), p < .001], fair/poor quality of life (QOL) [OR = 7.2 (95%CI 3.6-14.2), p < .001] and EFV exposure [OR = 1.6(95%CI 1.1-2.3), p = .01], were independently associated with having anxiety or depression. Our findings demonstrated that prevalence of depression and anxiety was low amongst virally suppressed, long-term antiretroviral-treated HIV-infected individuals. Some key characteristics such as the female sex, poor adherence, poor/fair QOL and EFV exposure are associated with anxiety and depression. These factors can be used to distinguish who would need a more in-depth evaluation for these psychiatric disorders. PMID- 27683951 TI - Number Density Distribution of Small Particles around a Large Particle: Structural Analysis of a Colloidal Suspension. AB - Some colloidal suspensions contain two types of particles-small and large particles-to improve the lubricating ability, light absorptivity, and so forth. Structural and chemical analyses of such colloidal suspensions are often performed to understand their properties. In a structural analysis study, the observation of the number density distribution of small particles around a large particle (gLS) is difficult because these particles are randomly moving within the colloidal suspension by Brownian motion. We obtain gLS using the data from a line optical tweezer (LOT) that can measure the potential of mean force between two large colloidal particles (PhiLL). We propose a theory that transforms PhiLL into gLS. The transform theory is explained in detail and tested. We demonstrate for the first time that LOT can be used for the structural analysis of a colloidal suspension. LOT combined with the transform theory will facilitate structural analyses of the colloidal suspensions, which is important for both understanding colloidal properties and developing colloidal products. PMID- 27683950 TI - Pediatric traumatic brain injury affects multisensory integration. AB - OBJECTIVE: To investigate the impact of pediatric traumatic brain injury (TBI) on multisensory integration in relation to general neurocognitive functioning. METHOD: Children with a hospital admission for TBI aged between 6 and 13 years (n = 94) were compared with children with trauma control (TC) injuries (n = 39), while differentiating between mild TBI without risk factors for complicated TBI (mildRF-; n = 19), mild TBI with >=1 risk factor (mildRF+; n = 45), and moderate/severe TBI (n = 30). We measured set-shifting performance based on visual information (visual shift condition) and set-shifting performance based on audiovisual information, requiring multisensory integration (audiovisual shift condition). Effects of TBI on set-shifting performance were traced back to task strategy (i.e., boundary separation), processing efficiency (i.e., drift rate), or extradecisional processes (i.e., nondecision time) using diffusion model analysis. General neurocognitive functioning was measured using estimated full scale IQ (FSIQ). RESULTS: The TBI group showed selectively reduced performance in the audiovisual shift condition (p = .009, Cohen's d = -0.51). Follow-up analyses in the audiovisual shift condition revealed reduced performance in the mildRF+ TBI group and moderate/severe TBI group (ps <= .025, ds <= -0.61). These effects were traced back to lower drift rate (ps <= .048, ds <= -0.44), reflecting reduced multisensory integration efficiency. Notably, accuracy and drift rate in the audiovisual shift condition partially mediated the relation between TBI and FSIQ. CONCLUSION: Children with mildRF+ or moderate/severe TBI are at risk for reduced multisensory integration efficiency, possibly contributing to decreased general neurocognitive functioning. (PsycINFO Database Record PMID- 27683952 TI - Epidemiology of football (soccer) injuries in the 2012/2013 and 2013/2014 seasons of the Italian Serie A. AB - Epidemiological studies on football (soccer) injuries are needed to assess both the magnitude of the problem and the effectiveness of preventive programmes. However, few data are available for Italy, which hosts one of the main football leagues in Europe. In this study, we aimed to describe the epidemiology of football injuries in the 2012/2013 and 2013/2014 seasons of the Italian Serie A. Information about injury location, type, date of occurrence and duration of absence was obtained from www.football-lineups.com , a free collaborative international database on football. Overall, 363 injuries occurred throughout the two seasons affecting 286 players. The most commonly reported injuries were thigh strain and knee injury, which accounted for 42% and 19% of all injuries, respectively. Injury incidence increased with age and was particularly higher from August to October. Results suggest that injury prevention strategies should be introduced from the preseason to reduce the risk of injuries, especially muscle strains. PMID- 27683953 TI - Downregulation of lysosomal and further gene expression characterization in lung cancer patients with bone metastasis. AB - Molecular and functional mechanisms of bone metastases were poorly understood. This study was to screen out differentially expressed genes (DEGs) and functional proteins in bone metastases from lung for better understanding of the molecular and functional mechanisms. Our results suggested CTSS, CTSD, MX1, NKX2-1 might play a decisive role in bone metastasis. Collectively, these results demonstrated that bone metastasis from lung cancer would lead to changes in lysosome function, which may affect the decomposition and elimination of old bone matrix, thus affecting bone turnover. In addition, our findings provided new insights into the prediction and treatment of bone metastases. PMID- 27683955 TI - Evidence of Coupling between the Motions of Water and Peptides. AB - Studies of protein dynamics at low temperatures are generally performed on hydrated powders and not in biologically realistic solutions of water because of water crystallization. However, here we avoid the problem of crystallization by reducing the size of the biomolecules. We have studied oligomers of the amino acid l-lysine, fully dissolved in water, and our dielectric relaxation data show that the glass transition-related dynamics of the oligomers is determined by the water dynamics, in a way similar to that previously observed for solvated proteins. This implies that the crucial role of water for protein dynamics can be extended to other types of macromolecular systems, where water is also able to determine their conformational fluctuations. Using the energy landscape picture of macromolecules, the thermodynamic criterion for such solvent-slaved macromolecular motions may be that the macromolecules need the entropy contribution from the solvent to overcome the enthalpy barriers between different conformational substates. PMID- 27683954 TI - Novel model of double transgenic mouse results in autoimmune diabetes in males. AB - Identifying the type of diabetogenic CD8+ T cells that initiate autoimmune diabetes (AID) is a critical step in designing appropriate strategies for the early detection of beta cell-directed autoimmunity and its progression to diabetes. We generated a novel double transgenic (Tg) mouse model on the naturally diabetes resistant C57Bl/6 background, co-expressing two transgenes including a specific TCR anti-lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) carried by CD8+ T cells and LCMV-NP (as neo-self antigen) expressed by pancreatic beta cells. The resulting double Tg mouse showed partial thymic deletion of the NP-specific CD8+ T cells. The escaping autoreactive NP-specific CD8+ T cells joining the periphery were activated and gained effector functions. Both male and female mice mounted anti-NP antibodies, but only one-fourth adult males spontaneously developed AID. Significant upregulation of the CD44 and CD122 markers as compared to healthy male and female mice characterized the phenotype of diabetogenic CD8+ T cells in diabetic male mice. We also show that only 10% of these CD8+ T cells expressed programmed death 1 receptor (PD-1). Together, these results suggest that in our double Tg mouse model, Ag-specific effector CD44+CD122+PD-1-CD8+ T cell subpopulation is associated with the pathogenesis of AID. PMID- 27683956 TI - Emotional prosody effects on verbal memory in older and younger adults. AB - Prosody, or the way things are said, can modify the meaning of utterances making qualitatively different affective prosodies useful for understanding how auditory affective information is processed and remembered. In this study, we collected behavioral data from 225 younger (M age = 20.8 years, SD = 2.5 years; 119 males) and 225 older adults (M age = 71.6 years, SD = 6.5 years; 119 males) in order to examine age differences in emotional prosody effects on verbal memory. Participants were randomly divided into three subgroups according to different prosody listening conditions (positive, negative, and neutral) and prosody effects on a yes-no recognition memory task were investigated. The results showed how older adults who listened to the story read with a neutral prosody remembered more words than those who listened to the same story with a positive or negative prosody. Younger adults showed no valence effects. Our findings highlighted an age and affective prosody interaction that affects remembering in older adults alone. PMID- 27683957 TI - Effect of the binding interaction of an emissive niacin derivative on the conformation and activity of a model plasma protein: A spectroscopic and simulation-based approach. AB - The present work demonstrates a detailed photophysics of bio-active drug-like acid viz., 2-hydroxynicotinic acid (2-HNA) and its interaction with a model plasma protein Bovine Serum Albumin (BSA). The drug which is in essence a vitamin B3 derivative, is capable of exhibiting ultrafast lactim-lactam cross-over response and thereby the modulation of the lactam emission within the bio environment of the protein has been depicted spectroscopically to reveal the drug protein interaction. Apart from evaluating the binding constant, the probable location of the neutral drug molecule within the protein cavity (hydrophobic subdomain IIIA) has been explored by AutoDock-based blind docking simulation technique. In this microheterogeneous medium, slow solvent reorientation time with respect to the emissive lifetime of the drug explicate the Red Edge Effect (REE). To complement the findings about the binding process, chaotrope-induced protein denaturation has also been inspected. The probe also illustrates a perceptible difference in rotational relaxation time in confined medium than in aqueous medium which strengthen our verdict. Unfolding of the protein in the presence of the drug molecule has been probed by the decrease of the alpha helical content, obtained via circular dichroism (CD) spectroscopy, which is also supported by the gradual slaughter of the esterase activity of the protein in the presence of the drug molecule. PMID- 27683958 TI - An overview of drug delivery vehicles for cancer treatment: Nanocarriers and nanoparticles including photovoltaic nanoparticles. AB - Cancer is a complicated disease for which finding a cure presents challenges. In recent decades, new ways to treat cancer are being sought; one being nanomedicine, which manipulates nanoparticles to target a cancer and release drugs directly to the cancer cells. A number of cancer treatments based on nanomedicine are under way and mostly are in preclinical trials owing to challenges in administration, safety, and effectiveness. One alternative method for drug delivery is the use of photovoltaic nanoparticles, which has the potential to deliver drugs via light activation. The concepts are based on standard photovoltaic cell that holds opposite charges on its surfaces and releases drugs when charge intensity or polarity changes upon photo-stimulation such as from a laser source or sunlight. This review will cover some recent progress in cancer treatment using nanoparticles, including photovoltaic nanoparticles. PMID- 27683960 TI - In Vivo Gene Transfer to Schwann Cells in the Rodent Sciatic Nerve by Electroporation. AB - The formation of the myelin sheath by Schwann cells (SCs) is essential for rapid conduction of nerve impulses along axons in the peripheral nervous system. SC selective genetic manipulation in living animals is a powerful technique for studying the molecular and cellular mechanisms of SC myelination and demyelination in vivo. While knockout/knockin and transgenic mice are powerful tools for studying SC biology, these methods are costly and time consuming. Viral vector-mediated transgene introduction into the sciatic nerve is a simpler and less laborious method. However, viral methods have limitations, such as toxicity, transgene size constraints, and infectivity restricted to certain developmental stages. Here, we describe a new method that allows selective transfection of myelinating SCs in the rodent sciatic nerve using electroporation. By applying electric pulses to the sciatic nerve at the site of plasmid DNA injection, genes of interest can be easily silenced or overexpressed in SCs in both neonatal and more mature animals. Furthermore, this in vivo electroporation method allows for highly efficient simultaneous expression of multiple transgenes. Our novel technique should enable researchers to efficiently manipulate SC gene expression, and facilitate studies on SC development and function. PMID- 27683959 TI - Multifaceted Assessment of Health Literacy in People Receiving Dialysis: Associations With Psychological Stress and Quality of Life. AB - Health literacy (HL) refers to a person's ability to engage effectively with health information and services. We aimed to describe the HL of people receiving dialysis and the factors associated with it. A cross-sectional design was used, with demographic and clinical data as predictors. Participants were people receiving dialysis at a metropolitan health service in Melbourne, Australia. Health consumers with conditions not requiring dialysis were included for comparison. The Health Literacy Questionnaire, Kidney Disease Quality of Life-36, and Depression Anxiety Stress Scales-21 were administered. Participants (M age = 68.2 +/- 13.7 years; n = 57 males) were 76 people receiving hemodialysis within a dialysis unit, 16 people receiving home peritoneal dialysis, and 8 people receiving home hemodialysis. Participants scored higher on the HL domains social support for health and engagement with health care providers but lower on active management of health than the comparison group (n = 813). Hierarchical cluster analysis revealed 2 clusters within the dialysis sample representing higher (n = 43) and lower (n = 57) profiles of HL. The higher HL cluster reported better quality of life across 4 of 5 domains of the Kidney Disease Quality of Life-36, fewer symptoms of depression and anxiety, and higher serum albumin (mean difference = 2.06 g/L, p = .04) than the lower HL cluster. These results show that people receiving dialysis feel better supported and informed about their health than other health consumers but are less active in managing it. Higher HL is associated with better mental health and quality of life. Identifying HL characteristics may help direct specific interventions to improve patient education and support. PMID- 27683961 TI - "Phagosome Closure Assay" to Visualize Phagosome Formation in Three Dimensions Using Total Internal Reflection Fluorescent Microscopy (TIRFM). AB - Phagocytosis is a mechanism used by specialized cells to internalize and eliminate microorganisms or cellular debris. It relies on profound rearrangements of the actin cytoskeleton that is the driving force for plasma membrane extension around the particle. In addition, efficient engulfment of large material relies on focal exocytosis of intracellular compartments. This process is highly dynamic and numerous molecular players have been described to have a role during phagocytic cup formation. The precise regulation in time and space of all of these molecules, however, remains elusive. In addition, the last step of phagosome closure has been very difficult to observe because inhibition by RNA interference or dominant negative mutants often results in stalled phagocytic cup formation. We have set up a dedicated experimental approach using total internal reflection fluorescence microscopy (TIRFM) combined with epifluorescence to monitor step by step the extension of pseudopods and their tips in a phagosome growing around a particle loosely bound to a coverslip. This method allows us to observe, with high resolution the very tips of the pseudopods and their fusion during closure of the phagosome in living cells for two different fluorescently tagged proteins at the same time. PMID- 27683964 TI - Remission of Marginal Zone Lymphoma After HCV Eradication With New Direct Antiviral Agents. PMID- 27683962 TI - An obesity paradox: an inverse correlation between body mass index and atherosclerosis of the aorta. AB - BACKGROUND AND AIMS: Morbid obesity generally has been associated with higher morbidity and mortality for a variety of diseases. However, a number of exceptions to this have been reported and referred to as the "obesity paradox." The purpose of the present study was to obtain objective data on aortic atherosclerosis and its relationship to body mass index (BMI, kg/m2), based on autopsy findings in a large cohort of overweight and obese decedents. METHODS: Decedents were >=18 years who had autopsies between 2003 and 2014, a subset of whom were morbidly obese (BMI>=40). Autopsy findings were reviewed and compared to a control group (BMI<40) who had consecutive autopsies performed between January 2013 and June 2014. Atherosclerosis was assessed by gross pathologic examination using a semiquantitative grading scale (from 0 to 3), and for statistical analysis, the scores were stratified into two groups: nonsevere (<2) or severe (>=2). RESULTS: There were 304 decedents in the study: 66 were morbidly obese (BMI>=40), 94 were either Class I or II obese (BMI 30-40), 127 were either overweight (BMI 25.0-29.9) or normal weight (BMI 20-24.9), and 17 were underweight (BMI<20). Decedents with mild atherosclerosis were significantly younger than those with severe disease (55.2 vs. 67.3, P<.0001). Decedents were further stratified by age and BMI. Univariate analysis revealed that decedents >60 years were more likely to have severe atherosclerosis than those <=60 years (61% vs. 30%, P<.0001). There was a highly significant (P=.008) inverse relationship between severe aortic atherosclerosis and BMI. Twenty of 66 decedents (30%) with a BMI>=40 had severe atherosclerosis vs. 122 of 238 decedents (51%) with BMIs<40 (P=.001). As BMI increased, the probability of developing severe disease decreased. Hypertension increased the probability of having severe atherosclerosis (54% vs. 33%, P=.007). After adjusting for other covariates, multivariable analysis revealed that age and hypertension were still positively correlated with the severity of atherosclerosis (P=.014 and 0.028, respectively), and the inverse relationship between BMI and atherosclerosis remained (adjusted relative risk of BMI>=40 vs. <40=0.64, 95% confidence interval: 0.4-1; P=.03). CONCLUSIONS: Our data extend the previously described obesity paradox to another disease entity, atherosclerosis of the aorta. Morbid obesity appeared to have a protective effect for developing severe aortic atherosclerosis, for the reasons for which are yet to be determined. However, the mean age at death of decedents with BMIs>=40 was younger than those with BMIs in the 20-30 range (55.9 vs. 63.2 years, P=.001), confirming that morbid obesity was not associated with increased longevity. PMID- 27683963 TI - The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis. AB - BACKGROUND: Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. METHODS: Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. RESULTS: Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. CONCLUSIONS: Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention. PMID- 27683965 TI - Endoscopic Management of Recurrent Dysphagia in a Patient With Allgrove Syndrome. PMID- 27683966 TI - Sport psychiatry and psychotherapeutic intervention, circa 2016. AB - The focus of this paper is to provide an update on the use of psychotherapy as a treatment in sport psychiatry, and the use of this approach to address common psychiatric issues encountered with this population. Specifically, family therapy, individual therapy, and group psychotherapy prescribed alone, or in combination with medication, will be examined as methods to manage issues/disorders often associated with athletes. These include obsessive compulsive rituals and perfectionism, and aggressive and risky behaviours, such as gambling, infidelity, substance use, and suicidal ideation, narcissism, and aggression in the context of individual and team competitive sports. PMID- 27683967 TI - Adult separation anxiety disorder in complicated grief: an exploratory study on frequency and correlates. AB - INTRODUCTION: Complicated grief (CG) has been the subject of increasing attention in the past decades but its relationship with separation anxiety disorder (SEPAD) is still controversial. The aim of the current study was to explore the prevalence and clinical significance of adult SEPAD in a sample of help-seeking individuals with CG. METHODS: 151 adults with CG, enrolled in a randomized controlled trial comparing the effectiveness of (CG) treatment to that of interpersonal therapy, were assessed by means of the Inventory of Complicated Grief (ICG), the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression (HAM-D), the Work and Social Adjustment Scale (WSAS), the Adult Separation Anxiety Questionnaire (ASA-27), the Grief Related Avoidance Questionnaire (GRAQ), the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), and the Impact of Events Scale (IES). RESULTS: 104 (68.9%) individuals with CG were considered to have SEPAD (ASA-27 score >=22). Individuals with SEPAD were more likely to have reported a CG related to the loss of another close relative or friend (than a parent, spouse/partner or a child) (p=.02), as well as greater scores on the ICG (p=<.001), PDEQ (p=.004), GRAQ (p<.001), intrusion (p<.001) and avoidance (p=<.001) IES subscales, HAM-D (p<.001) and WSAS (p=.006). ASA-27 total scores correlated with ICG (p<.0001), PDEQ (p<.001) GRAQ (p<.0001) scores and both the IES intrusion (p<.0001) and IES avoidance (p<.0001) subscale scores. People with SEPAD had higher rates of lifetime post-traumatic stress disorder (PTSD) (p=.04) and panic disorder (PD) (p=.01). CONCLUSIONS: SEPAD is highly prevalent among patients with CG and is associated with greater symptom severity and impairment and greater comorbidity with PTSD and PD. Further studies will help to confirm and generalize our results and to determine whether adult SEPAD responds to CG treatment and/or moderates CG treatment response. PMID- 27683968 TI - Synergistic effect of PEGylation and pentoxifylline addition on immunoprotection of pancreatic islets. AB - In this study, a method is proposed to reduce immunological response of immune system against Langerhans islets by PEGylation of islets combined with adjuvant therapy. For this purpose, the best composition for a mixture of succinimidyl valeric acid activated mPEG (mPEG-SVA) with different molecular weights (MWs) and for a mixture of succinimidyl carbonate activated mPEG (mPEG-SC) with different MWs was determined separately. Then, the effect of pentoxifylline (PTX) as an adjuvant drug on immunological response against PEGylated islets at best mPEG composition was studied. The extent of mPEGs reaction, the amount of interlukin-2 (IL-2) and perforin secretion, and the viability of lymphocytes and islets in homo and co-cultures in the presence of PTX at different concentrations were considered for the in vitro evaluation of the proposed method. It was found, that a mixture of mPEG-SVA with MWs of 10 and 5 kDa at a composition of 75 and 25%, respectively, was the best formulation. Also, the addition of PTX drug to co culture medium increased the protection of PEGylated islets against immune system and a concentration of 75 MUg mL-1 of PTX was suitable for islet protection with no adverse effect on immune cells. PMID- 27683969 TI - Metabolic demand and muscle damage induced by eccentric cycling of knee extensor and flexor muscles. AB - : The aim of this study was to examine the metabolic demand and extent of muscle damage of eccentric cycling targeting knee flexor (FLEX) and knee extensor (EXT) muscles. METHODS: Eight sedentary men (23.3 +/- 0.7 y) underwent two eccentric cycling sessions (EXT and FLEX) of 30 min each, at 60% of the maximum power output. Oxygen consumption (VO2), heart rate (HR) and rated perceived exertion (RPE) were measured during cycling. Countermovement and squat jumps (CMJ and SJ), muscle flexibility, muscle soreness and pain pressure threshold (PPT) of knee extensor and flexor muscles were measured before, immediately after and 1-4 days after cycling. RESULTS: FLEX showed greater VO2 (+23%), HR (+14%) and RPE (+18%) than EXT. CMJ and SJ performance decreased similarly after cycling. Muscle soreness increased more after EXT than FLEX and PPT decreased in knee extensor muscles after EXT and decreased in knee flexor muscles after FLEX. Greater loss of muscle flexibility in knee flexor muscles after FLEX was observed. CONCLUSION: Eccentric cycling of knee flexor muscles is metabolically more demanding than that of knee extensors, however muscle damage induced is similar. Knee flexors experienced greater loss of muscle flexibility possibly due to increased muscle stiffness following eccentric contractions. PMID- 27683970 TI - Effects of Semont maneuver on benign paroxysmal positional vertigo: a meta analysis. AB - BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most common type of peripheral vertigo. This study aimed to evaluate the effects of the Semont maneuver (SM) for BPPV treatment, compared with other methods. METHODS: Studies were selected in relevant databases under pre-defined criteria up to June 2015. The Cochrane evaluation system was used to assess the quality of the studies. Effect size was indicated as a risk-ratio (RR) with corresponding 95% confidential interval (CI). Statistical analysis was conducted under a randomized or fixed-effects model. Sub-group analysis was performed. RESULTS: Ten studies were included in the meta-analysis. All of the studies presented a low attrition bias, but a high selection and reporting bias. SM had a much higher recovery rate (SM vs no treatment: RR = 2.60, 95% CI = 1.97-3.44, p < 0.01; SM vs sham: RR = 4.89, 95% CI = 3.01-7.94, p < 0.01), and lower recurrence rate than those from controls (SM vs no treatment: RR = 0.11, 95% CI = 0.04-0.31, p < 0.01). Overall, SM had similar outcomes with Epley maneuver (EM) and Brandt-Daroff exercise (BDE) in terms of recovery rate, recurrence rate, and side-effects. CONCLUSION: SM is as effective as EM and BDE for BPPV treatment. PMID- 27683971 TI - Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma. AB - We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma. PMID- 27683972 TI - Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography. AB - Membrane proteins (MPs) are essential components of cellular membranes and primary drug targets. Rational drug design relies on precise structural information, typically obtained by crystallography; however MPs are difficult to crystallize. Recent progress in MP structural determination has benefited greatly from the development of lipidic cubic phase (LCP) crystallization methods, which typically yield well-diffracting, but often small crystals that suffer from radiation damage during traditional crystallographic data collection at synchrotron sources. The development of new-generation X-ray free-electron laser (XFEL) sources that produce extremely bright femtosecond pulses has enabled room temperature data collection from microcrystals with no or negligible radiation damage. Our recent efforts in combining LCP technology with serial femtosecond crystallography (LCP-SFX) have resulted in high-resolution structures of several human G protein-coupled receptors, which represent a notoriously difficult target for structure determination. In the LCP-SFX technique, LCP is recruited as a matrix for both growth and delivery of MP microcrystals to the intersection of the injector stream with an XFEL beam for crystallographic data collection. It has been demonstrated that LCP-SFX can substantially improve the diffraction resolution when only sub-10 um crystals are available, or when the use of smaller crystals at room temperature can overcome various problems associated with larger cryocooled crystals, such as accumulation of defects, high mosaicity and cryocooling artifacts. Future advancements in X-ray sources and detector technologies should make serial crystallography highly attractive and practicable for implementation not only at XFELs, but also at more accessible synchrotron beamlines. Here we present detailed visual protocols for the preparation, characterization and delivery of microcrystals in LCP for serial crystallography experiments. These protocols include methods for conducting crystallization experiments in syringes, detecting and characterizing the crystal samples, optimizing crystal density, loading microcrystal laden LCP into the injector device and delivering the sample to the beam for data collection. PMID- 27683973 TI - Monosomal karyotype is not a predictor of dismal outcome in childhood de novo acute myeloid leukemia. AB - Monosomal karyotype (MK) is known as a far end of the unfavorable cytogenetics in adult acute myeloid leukemia (AML), while available data in childhood AML is scarce. In this study, we investigated the prevalence and prognostic value of MK with retrospectively analyzed 119 patients newly diagnosed with childhood de novo AML. Ten patients (8.4%) revealed to have MK. All MK-positive (MK(+)) AML were associated with complex cytogenetic abnormalities and belonged to the cytogenetic adverse-risk group. Nine of MK(+) patients (90%) achieved complete remission. The event-free survival (EFS) and overall survival (OS) of MK(+) adverse group were comparable to the ESF and OS of MK-negative non-adverse group (EFS 60.0+/-15.5% vs 59.0+/-5.1%, P=0.925; OS 70.0+/-14.5% vs 58.1+/-5.3%, P=0.696). In multivariate analysis, MK was not an independent adverse prognostic factor for EFS (hazard ratio 0.45, 95% C.I. 0.13-1.50, P=0.194). In addition, 7 of 9 MK(+) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) survived event-free, with a median follow-up of 64 months. In conclusion, MK did not act as an adverse prognostic factor in childhood de novo AML. Allogeneic HSCT might have contributed to the excellent outcome of MK(+) childhood de novo AML. PMID- 27683975 TI - Multifidus Muscle Atrophy Not Observed Following Two-segment Anterior Interbody Fusion: A Rabbit Model Study With a 12-Month Follow-up. AB - STUDY DESIGN: Experimental study evaluated magnetic resonance imaging (MRI) and histologic changes in the multifidus muscle after anterior spinal fusion. OBJECTIVE: To determine the effect of spinal fusion on the multifidus muscle in an anterior rabbit model through the use of MRI and histologic evaluation. SUMMARY OF BACKGROUND DATA: Retraction and splitting approach are known to be important factors in postoperative injury and atrophy of the multifidus muscle. The effect and possible mechanism of spinal fusion as an independent factor remains unknown. METHODS: Thirty-six New Zealand white rabbits were divided into two groups. Animals in the fusion group underwent two-level anterior spinal fusion whereas those in the control group underwent similar surgery without spinal fusion. The status of the multifidus muscle was evaluated with MRI and histological analysis at preoperative, 3 weeks, 6 weeks, 3 months, 6 months, and 12 months postoperatively. RESULTS: All rabbits in the fusion group achieved solid fusion. The mean T1-weighted and T2-weighted signal intensity ratios of gross multifidus to psoas muscles were all approximately 1.0 postoperatively, with no remarkable difference between the groups. The mean lesser diameter of myofibrils in either group did not significantly differ between the preoperative and postoperative specimens. There was no significant fibrotic change or fatty degeneration for either group. Decrease in acetylcholine activity or granular degeneration of the neuromuscular junction were not observed, and normal shape and size were found in nearly all samples at all time points in both groups (P > 0.05). CONCLUSION: After two-segment anterior spinal fusion, multifidus atrophy was not observed throughout a 12-month follow up. The rabbit model of anterior fusion is better suited to study the effect of fusion alone on the status of the multifidus muscle. LEVEL OF EVIDENCE: 3. PMID- 27683974 TI - Cross-resistance and synergy with bendamustine in chronic lymphocytic leukemia. AB - Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant. In contrast, some resistant CLL cells retained moderate sensitivity to dADO/PEN. Like FLU and CLB, BEN induced apoptosis through both the mitochondrial and death receptor pathways. There was a greater increase in DNA double-strand breaks (DSB) following FLU, as compared to BEN and CLB. Synergistic cytotoxicity was seen on combining BEN or CLB with FLU or dADO/PEN, but not when combining BEN with CLB. These results demonstrate that BEN acts as an alkylating agent, demonstrates cross-resistance to CLB and FLU and resistance to cells with a del 17p. Synergistic cytotoxic activity was seen between BEN and dADO/PEN suggesting that the combination of BEN and PEN should be evaluated in the clinic. PMID- 27683976 TI - Increased Total Anesthetic Time Leads to Higher Rates of Surgical Site Infections in Spinal Fusions. AB - STUDY DESIGN: A retrospective review of a consecutive series of spinal fusions comparing patient and procedural characteristics of patients who developed surgical site infections (SSIs) after spinal fusion. OBJECTIVE: It is known that increased surgical time (incision to closure) is associated with a higher rate of postoperative SSIs. We sought to determine whether increased total anesthetic time (intubation to extubation) is a factor in the development of SSIs as well. SUMMARY AND BACKGROUND DATA: In spine surgery for deformity and degenerative disease, SSI has been associated with operative time, revealing a nearly 10-fold increase in SSI rates in prolonged surgery. Surgical time is associated with infections in other surgical disciplines as well. No studies have reported whether total anesthetic time (intubation to extubation) has an association with SSIs. METHODS: Surgical records were searched in a retrospective fashion to identify all spine fusion procedures performed between January 2010 and July 2012. All SSIs during that timeframe were recorded and compared with the list of cases performed between 2010 and 2012 in a case-control design. RESULTS: There were 20 (1.7%) SSIs in this fusion cohort. On univariate analyses of operative factors, there was a significant association between total anesthetic time (Infection 7.6 +/- 0.5 hrs vs. no infection -6.0 +/- 0.1 hrs, P < 0.001) and increasing operative time (infection 5.5 +/- 0.4 hrs vs. no infection - 4.4 +/- 0.06 hrs, P < 0.01) with infections, whereas level of pathology and emergent surgery were not significant. On multivariate logistic analysis, BMI and total anesthetic time remained independent predictors of SSI whereas ASA status and operative time did not. CONCLUSION: Increasing BMI and total anesthetic time were independent predictors of SSIs in this cohort of over 1000 consecutive spinal fusions. LEVEL OF EVIDENCE: 3. PMID- 27683977 TI - Anterior Spinal Overgrowth Is the Result of the Scoliotic Mechanism and Is Located in the Disc. AB - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To investigate the presence and magnitude of anterior spinal overgrowth in neuromuscular scoliosis and compare this with the same measurements in idiopathic scoliosis and healthy spines. SUMMARY OF BACKGROUND DATA: Anterior spinal overgrowth has been described as a potential driver for the onset and progression of adolescent idiopathic scoliosis (AIS). Whether this anterior overgrowth is specific for AIS or also present in nonidiopathic scoliosis has not been reported. METHODS: Supine computed tomography (CT) scans of thirty AIS patients (thoracic Cobb 21-81 degrees ), thirty neuromuscular (NM) scoliotic patients (thoracic Cobb 19-101 degrees ) and 30 nonscoliotic controls were used. The difference in length in per cents between the anterior and posterior side {[(DeltaA-P)/P]*100%, abbreviated to A-P%} of each vertebral body and intervertebral disc, and between the anterior side of the spine and the spinal canal (A-C%) were determined. RESULTS: The A-P% of the thoracic curves did not differ between the AIS (+1.2 +/- 2.2%) and NM patients (+0.9 +/- 4.1%, P = 0.663), both did differ, however, from the same measurements in controls (-3.0 +/- 1.6%; P < 0.001) and correlated linearly with the Cobb angle (AIS r = 0.678, NM r = 0.687). Additional anterior length was caused by anterior elongation of the discs (AIS: A-P% disc +17.5 +/- 12.7% vs. A-P% body 2.5 +/- 2.6%; P < 0.001, NM: A-P% disc +19.1 +/- 18.0% vs. A-P% body -3.5 +/- 5.1%; P < 0.001). The A-C% T1-S1 in AIS and NM patients were similar (+7.9 +/- 1.8% and +8.7 +/- 4.0%, P = 0.273), but differed from the controls (+4.2 +/- 3.3%; P < 0.001). CONCLUSION: So called anterior overgrowth has been postulated as a possible cause for idiopathic scoliosis, but apparently it occurs in scoliosis with a known origin as well. This suggests that it is part of a more generalized scoliotic mechanism, rather than its cause. The fact that the intervertebral discs contribute more to this increased anterior length than the vertebral bodies suggests an adaptation to altered loading, rather than a primary growth disturbance. LEVEL OF EVIDENCE: 4. PMID- 27683979 TI - ? AB - The Royal Air Force recently sacked an enrolled nurse who had given five years service. Her sin? She was a lesbian. Nothing else. Her nursing skills weren't open to question, there was no sudden drop in the standard of care she gave to patients. In fact, the RAF was willing to invest in her future and she was undertaking a conversion course. PMID- 27683978 TI - Potentiodynamic Corrosion Testing. AB - Different metallic materials have different polarization characteristics as dictated by the open circuit potential, breakdown potential, and passivation potential of the material. The detection of these electrochemical parameters identifies the corrosion factors of a material. A reliable and well-functioning corrosion system is required to achieve this. Corrosion of the samples was achieved via a potentiodynamic polarization technique employing a three-electrode configuration, consisting of reference, counter, and working electrodes. Prior to commencement a baseline potential is obtained. Following the stabilization of the corrosion potential (Ecorr), the applied potential is ramped at a slow rate in the positive direction relative to the reference electrode. The working electrode was a stainless steel screw. The reference electrode was a standard Ag/AgCl. The counter electrode used was a platinum mesh. Having a reliable and well functioning in vitro corrosion system to test biomaterials provides an in expensive technique that allows for the systematic characterization of the material by determining the breakdown potential, to further understand the material's response to corrosion. The goal of the protocol is to set up and run an in vitro potentiodynamic corrosion system to analyze pitting corrosion for small metallic medical devices. PMID- 27683980 TI - ? AB - Abracadahra: a young visitor to the new children's out-patient department at Airedale General Hospital in Yorkshire enjoys the magic created by Paul Sunderland, one of the performers who provided entertainment at the official opening recently. The clinic is staffed by experienced children's nurses and nursery nurses. PMID- 27683982 TI - School nurse cleared by council over sex lessons. AB - The school nurse accused of giving over-explicit sex education to children in Leeds, has been vindicated by the official inquiry into the affair. PMID- 27683981 TI - Lesbian nurse sacked by RAF. AB - The Royal Air Force has sacked an enrolled nurse after a colleague revealed she was a lesbian. Jeanette Smith has vowed to fight the decision to terminate her military career after she became a victim of the latest purge of homosexuals from the armed forces. PMID- 27683983 TI - Panel decides on Ralph grievance. AB - The panel investigating complaints against embattled UKCC Registrar Colin Ralph was understood to have upheld the grievance taken out against him by senior staff, as Nursing Standard went to press. PMID- 27683984 TI - South Tees to vote on 8.8% offer. AB - Unions at South Tees Acute Hospitals NHS Trust are to ballot members on local trust contracts on whether to accept an 8.8 per cent pay package. PMID- 27683985 TI - Evidence lacking' on water births. AB - The case of a full term baby boy who became ill after being delivered in a birthing tub at North Middlesex Hospital in London is highlighted in a British Medical Journal report which says reliable evidence is lacking about water births. PMID- 27683986 TI - Hospital faces probe over disciplinary delay. AB - The UKCC is likely to question the hospital which dismissed a nurse over an unsigned drug sheet as to why it took four months to report the matter to the Professional Conduct Committee. PMID- 27683987 TI - Pay schemes based on trust performance are inadequate. AB - A shift in Government thinking away from individual performance-related pay schemes for nurses in favour of deals based on their trust's wider performance has been dismissed by the RCN as inadequate. PMID- 27683988 TI - Singing nurse to contest suspension. AB - A community nurse who greeted an elderly patient by singing the 1960s Cher hit 'Bang! Bang! you shot me down', is now fighting a suspension after being reported to managers by a colleague. PMID- 27683989 TI - Massive coverage for re-admission survey. AB - Widespread national and local media coverage followed the publication of the results of Nursing Standard's joint survey with BBC TV's Here and Now' programme on patient readmission rates. PMID- 27683990 TI - RCN and DoH set to clash on confidentiality guidelines. AB - The Department of Health and the professional bodies' joint working party on patient confidentiality appear to be headed for a major clash over the Government's newly-released draft guidelines on confidentiality. PMID- 27683991 TI - New report out on inspectors. AB - Teams inspecting private nursing homes and hospitals are 'seriously' understaffed and underresourced, says an RCN report to he launched tomorrow. PMID- 27683993 TI - ? AB - Home and garden: the Hyde Nursing Home, officially opened in Cheshire last week, includes a garden dedicated to Mary Seacole, the black nurse who worked with Florence Nightingale. Pictured, left to right, are: Staff nurse Lynn Pritchard, home manager Hazel Shaw and care assistant Sandra Harrison. PMID- 27683995 TI - Jobs boost for students. AB - A Shropshire trust has offered qualified nursing jobs to all its students who finished training this year because it does not want to waste its investment in their education. PMID- 27683992 TI - HVs concerned over guidance on smacking. AB - Health visitors have expressed concern over reports that the Government may give parents and childminders freedom to smack. PMID- 27683996 TI - Demand for investment in MH training. AB - Government investment in staff training was demanded by the Royal College of Nursing last week in the wake of a report which claimed 13 murders carried out by mentally ill people could have been avoided. PMID- 27683997 TI - New book on workers' stress. AB - Examples of workers whose mental and physical health has been damaged by stress at work have been published in a book by the London Hazards Centre. PMID- 27683998 TI - Derbyshire nurses hit back. AB - Derbyshire nurses have hit back after accusations in recent press reports that they ignored a male patient who claimed he had to ring the ward on his mobile phone to get attention. PMID- 27683999 TI - Extra time for school nurses. AB - The Royal College of Nursing has won an important victory for school nurses carrying out the Government's national measles immunisation campaign, buying them extra time to complete work which was forced aside. PMID- 27684000 TI - ? AB - In the frame: Nurse Shantie Mohammed, currently a student on an RGN conversion course, was one of the entrants in an art competition organised at the Royal Hospitals NHS Trust in London. The contest was the first event organised by the hospital's new art support group and attracted paintings and sculpture from staff including nurses, doctors and porters, as well as patients. PMID- 27684001 TI - All-in-one baby vaccine launched. AB - A 'quadruple' vaccine which could help nurses reduce the number of injections needed by babies under the national immunisation programme was launched by Lederle-Praxis last week. PMID- 27684003 TI - Report suggests private health deals would increase union membership. AB - The Labour Party must be prepared to embrace the concept of private health care providers working in tandem with the NHS if it is to maintain a 'credible' health agenda, a report by the Independent Healthcare Association has warned. PMID- 27684004 TI - Education the key to family planning. AB - Nurses providing information on contraception and family planning in deprived Third World countries should be aware of their clients' educational levels, a report on contraception from the World Health Organization has said. PMID- 27684005 TI - US nurses back new bill in Congress. AB - The President of the American Nurses Association, Virginia Trotter Betts, has formally backed the troubled bill which would provide all Americans with universal health care coverage. PMID- 27684006 TI - Summer school welcomes Swaziland nurse. AB - A Swazi nurse made her first ever trip to a western country to attend the 14th International Summer School run by the RCN and Michigan State University's College of Nursing held in London recently. PMID- 27684007 TI - Nurse prescribing study sites announced. AB - The two colleges where nurses will study in preparation for the introduction of nurse prescribing pilot sites have been announced as the countdown to the scheme's introduction continues. PMID- 27684008 TI - RCN to establish advice group on travel and health. AB - A national travel health group to help nurses increase awareness of health risks abroad will be launched by the Royal College of Nursing in September. PMID- 27684009 TI - Child's needs not affected by state of parents' marriage. AB - The level to which the needs of children are met is not affected by the state of their parents' marriage, a US study claims. PMID- 27684011 TI - Japan's high-rise living linked to miscarriages. AB - Women living on the fifth floor and above in tower blocks are more than twice as likely to suffer a miscarriage, a Japanese study has claimed. PMID- 27684010 TI - Doctors fail to recognise distress signs in cancer patients. AB - Doctors are failing to identify areas where breast cancer sufferers are most profoundly affected, the results of a recent study in Devon have suggested. PMID- 27684012 TI - Diabetes care too patchy, claims report. AB - A shortage of diabetes specialist nurses and inadequate education of practice nurses has led to wide variations across the UK in the care of people with diabetes, a government commissioned report has claimed. PMID- 27684013 TI - Survival of people with cerebral palsy. AB - Survival rates of mild and moderately disabled children with cerebral palsy are not much lower than those for unaffected children, Liverpool researchers say. PMID- 27684014 TI - Suicide prevention called into doubt. AB - It is doubtful hat effect We suicide prevention strategies can be implemented either in primary care or mental health services, Scottish researchers report. PMID- 27684015 TI - Treatment for problem menopausal hot flushes. AB - Postmenopausal women unable to take oestrogens because they have breast cancer might gain relief from hot flushes by taking megestrol. PMID- 27684017 TI - Pink, Hands, red faces: UKCC bites back. AB - I thought that your readers may be interested to note that the UKCC's 'ostentatious' and 'expensive' office accommodation costs the UKCC a peppercorn rent of L250 pier annum. PMID- 27684016 TI - One-off injection to protect against 'flu? AB - The days of annual vaccinations to protect vulnerable groups against influenza might be numbered if trials of a new compound prove successful. PMID- 27684018 TI - Funny money for the ex-army mummies. AB - I welcome the news that Fiona Boag, the former nurse who seriously injured her back lifting a patient, was awarded a decent sum in compensation (L205,000 for back injury, News, July 27). PMID- 27684019 TI - There are too many hours in the day. AB - During my recent time as chair of Guy's Hospital Student Nurse Council, the most oft-repeated concern from students was that of the 10-12 hour shift. PMID- 27684020 TI - Missing: about 6,000 RCN members. AB - Your assistance is required in solving a mystery. There are reputedly over 6,000 Greater Glasgow Branch RCN members, but unfortunately the majority have not been seen at the branch meetings. Have they been kidnapped? Are they lost? PMID- 27684021 TI - Trust me, I'm a member of staff. AB - It might be of interest to health service managers to know that a colleague and myself co-ordinated a six- month project in which we led a group of eight staff providing counselling to all those working within our trust. PMID- 27684022 TI - The hippy, hippy shake-up. AB - I think I may have discovered the answer to the growing list of complaints about NI IS waiting lists under this Tory Government. Make sure you live in an area which has a Labour MP. PMID- 27684023 TI - How is it for you? AB - ... Unsupportive managers, job insecurity, an ever-changing working environment? PMID- 27684025 TI - Information exchange. AB - I am an enrolled nurse undertaking an open learning course and working on an elderly care unit. As part of my study I am revising our pain management/assessment practices and plan to introduce pain assessment tools to the unit. I would like any information on pain management or anyone's experience of using pain assessment tools on elderly care units. PMID- 27684024 TI - Please, have Mercy upon us. AB - Thank you very much to Nursing Standard for advertising the Mercy House Foundation last year when we needed new volunteers. Now we are having to raise L350,000 to provide a family respite centre for clients and families affected by HIV/AIDS. PMID- 27684026 TI - Nursing and social policy: care in context Nursing and social policy: care in context Gough P Maslin-Prothero S and Masterson A , Butterworth/Heinemann 304pp L14.95 0-7506-1872-8. AB - Nursing and Social Policy: Care in Context is written primarily for those students engaged on Project 2000 courses. Its catchment, however, is likely to be broader, perhaps, across the undergraduate areas in nursing and allied health care, as well as those new to management in nursing and those engaged in policy related work. PMID- 27684028 TI - Violence and Health Care Professionals Til Wykes , editor Chapman & Hall 266pp L14.99 0-412-46170-6. AB - Violence and Health Care Professionals is a logical, concise and detailed book adopting a multidisciplinary approach to this problem which affects every health care professional. PMID- 27684027 TI - Urological nursing Urological nursing C Laker Scutari Press 362pp L24.99 1 -871 364-84-1 [Formula: see text]. AB - Urological Nursing is a multicontributed book edited by Clive Laker. PMID- 27684029 TI - News from the society. AB - This supplement to Nursing Standard provides an important conduit for the Tissue Viability Society (TVS) because it reaches all those who are most involved in the maintenance of skin integrity. The effective working relationship between the Society, through its current and previous supplement editors, and Nursing Standard staff has now existed for over six years and I hope that it will continue to develop. PMID- 27684031 TI - DoH report focuses on leg ulcer research. AB - A report commissioned by the Department of Health containing a review of research into leg ulcer management was launched earlier this summer. PMID- 27684032 TI - New wound management package keeps nurses up-to-date. AB - A comprehensive teaching package for nurses involved in wound management has been launched. PMID- 27684030 TI - More pressure sore prevention research needed. AB - Comments by a top nurse at the Scottish Office that research into prevention of pressure sores had 'been done to death' have sparked controversy. PMID- 27684033 TI - Aspirin could improve ulcer healing rate. AB - The healing rate of chronic venous leg ulcers could be speeded up by aspirin, according to a study published in The Lancet. PMID- 27684035 TI - Listings. PMID- 27684034 TI - Wound care in three European countries. AB - With the advent of the Single European Act in 1987, it was envisaged that there should be greater co-operation within the European Union (EU). This has led to the need for nurses to communicate and work with their colleagues in other European countries. With this changing climate, it is therefore vital that nurses broaden their vision of nursing, and become aware of what is happening in hospitals in other countries. PMID- 27684036 TI - Laparoscopic pyelolithotomy versus percutaneous nephrolithotomy for treatment of large renal pelvic calculi (diameter >2 cm): a meta-analysis. AB - OBJECTIVE: To systematically assess the efficacy and safety of laparoscopic pyelolithotomy (LP) versus percutaneous nephrolithotomy (PCNL) for the treatment of renal pelvic calculi >2 cm. METHODS: We searched PubMed, Embase, Cochrane Library, and Google Scholar about LP and PCNL for the treatment of renal stones. The retrieval time ended in September 2015. Two reviewers independently assessed the quality of all included studies. The available data in the studies were analyzed using the RevMan 5.2 software. RESULTS: Four randomized controlled trials (RCTs) and nine Non-Randomized Concurrent Controlled Trials (NRCCTs) were included, involving a total of 766 patients. This meta-analysis showed that LP has a statistically higher stone-free rate than PCNL [I2 = 0, OR = 0.26 (95% CI 0.10-0.64), p = 0.003], lower drop in hemoglobin level [I2 = 0, difference in mean drop = -0.83 (95% CI -1.05 to -0.61), p < 0.00001] and lower postoperation fever [I2 = 0, OR = 0.36 (95% CI 0.14-0.89), p = 0.03], and PCNL is associated with a lower length of hospital stay [I2 = 74%, difference in mean of hospital stay = 0.72 (95% CI 0.04-1.40), p = 0.04]. CONCLUSION: LP is an alternative for the treatment of large solitary renal stone. LP may have a higher stone-free rate, lesser blood loss, lower postoperation fever rate, while PCNL may have a lower length of hospital stay. However, further well designed and large volume randomized controlled trials are needed to confirm these findings. PMID- 27684038 TI - Response to Calgani et al. PMID- 27684037 TI - Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial. AB - PURPOSE: Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. METHODS: In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. RESULTS: A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). CONCLUSION: A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456. PMID- 27684039 TI - Congenital heart defects in Noonan syndrome and RIT1 mutation. PMID- 27684040 TI - Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells. AB - Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG(-/-) recipients) are reconstituted with naive CD4(+) T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen. To study the potential role of antigen presenting cells (APCs) in the disease process, it is helpful to have an antigen-driven disease model, in which a defined commensal-derived antigen leads to colitis. An antigen driven-colitis model has hence been developed. In this model OT-II CD4(+) T cells, that can recognize only specific epitopes in the OVA protein, are transferred into RAG(-/ ) hosts challenged with CFP-OVA-expressing E. coli. This model allows the examination of interactions between APCs and T cells in the lamina propria. PMID- 27684042 TI - Nucleus-associated actin in Amoeba proteus. AB - The presence, spatial distribution and forms of intranuclear and nucleus associated cytoplasmic actin were studied in Amoeba proteus with immunocytochemical approaches. Labeling with different anti-actin antibodies and staining with TRITC-phalloidin and fluorescent deoxyribonuclease I were used. We showed that actin is abundant within the nucleus as well as in the cytoplasm of A. proteus cells. According to DNase I experiments, the predominant form of intranuclear actin is G-actin which is associated with chromatin strands. Besides, unpolymerized actin was shown to participate in organization of a prominent actin layer adjacent to the outer surface of nuclear envelope. No significant amount of F-actin was found in the nucleus. At the same time, the amoeba nucleus is enclosed in a basket-like structure formed by circumnuclear actin filaments and bundles connected with global cytoplasmic actin cytoskeleton. A supposed architectural function of actin filaments was studied by treatment with actin-depolymerizing agent latrunculin A. It disassembled the circumnuclear actin system, but did not affect the intranuclear chromatin structure. The results obtained for amoeba cells support the modern concept that actin is involved in fundamental nuclear processes that have evolved in the cells of multicellular organisms. PMID- 27684041 TI - Interstitial Lung Disease in India. Results of a Prospective Registry. AB - RATIONALE: Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. OBJECTIVES: To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. METHODS: Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's kappa was used to assess reliability of interobserver agreement. MEASUREMENTS AND MAIN RESULTS: A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's kappa: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. CONCLUSIONS: Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide. PMID- 27684043 TI - High-resolution tide projections reveal extinction threshold in response to sea level rise. AB - Sea-level rise will affect coastal species worldwide, but models that aim to predict these effects are typically based on simple measures of sea level that do not capture its inherent complexity, especially variation over timescales shorter than 1 year. Coastal species might be most affected, however, by floods that exceed a critical threshold. The frequency and duration of such floods may be more important to population dynamics than mean measures of sea level. In particular, the potential for changes in the frequency and duration of flooding events to result in nonlinear population responses or biological thresholds merits further research, but may require that models incorporate greater resolution in sea level than is typically used. We created population simulations for a threatened songbird, the saltmarsh sparrow (Ammodramus caudacutus), in a region where sea level is predictable with high accuracy and precision. We show that incorporating the timing of semidiurnal high tide events throughout the breeding season, including how this timing is affected by mean sea-level rise, predicts a reproductive threshold that is likely to cause a rapid demographic shift. This shift is likely to threaten the persistence of saltmarsh sparrows beyond 2060 and could cause extinction as soon as 2035. Neither extinction date nor the population trajectory was sensitive to the emissions scenarios underlying sea-level projections, as most of the population decline occurred before scenarios diverge. Our results suggest that the variation and complexity of climate-driven variables could be important for understanding the potential responses of coastal species to sea-level rise, especially for species that rely on coastal areas for reproduction. PMID- 27684044 TI - Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema. AB - Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among the most important players in the development and evolution of stroke-evoked brain edema is the hormone arginine-vasopressin and its receptors, V1a and V2. Recently, the V1a and V2 receptor blocker conivaptan has been attracting attention as a potential drug to reduce brain edema after stroke. However, animal models which involve conivaptan applications in stroke research need to be modified based on feasible routes of administration. Here the outcomes of 48 hr continuous intravenous (IV) are compared with intraperitoneal (IP) conivaptan treatments after experimental stroke in mice. We developed a protocol in which middle cerebral artery occlusion was combined with catheter installation into the jugular vein for IV treatment of conivaptan (0.2 mg) or vehicle. Different cohorts of animals were treated with 0.2 mg bolus of conivaptan or vehicle IP daily. Experimental stroke-evoked brain edema was evaluated in mice after continuous IV and IP treatments. Comparison of the results revealed that the continuous IV administration of conivaptan alleviates post-ischemic brain edema in mice, unlike the IP administration of conivaptan. We conclude that our model can be used for future studies of conivaptan applications in the context of stroke and brain edema. PMID- 27684045 TI - Long-term Analysis of Lip Augmentation With Superficial Musculoaponeurotic System (SMAS) Tissue Transfer Following Biplanar Extended SMAS Rhytidectomy. AB - Importance: To our knowledge, long-term, objective results of lip augmentation using superficial musculoaponeurotic system (SMAS) tissue transfer beyond 1 year have not been previously described. Objective: To evaluate the efficacy, longevity, and safety of lip augmentation using SMAS tissue transfer. Design, Setting, and Participants: A retrospective single-blind cohort study was designed to evaluate all patients who underwent surgical lip augmentation using SMAS following rhytidectomy between January 1, 2000, and November, 16, 2015, at a private facial plastic surgery practice in Birmingham, Alabama. Preoperative photographs of each patient served as controls and were compared with postoperative photographs at 3 months, 1 year, and 5 years after lip augmentation. A total of 104 images (from 26 individual patients) were reviewed by 12 blinded observers using a validated lip augmentation grading scale. Exposures: Lip augmentation using SMAS. Main Outcomes and Measures: Median lip volumes of all patients at each postoperative interval (3 months, 1 year, and 5 years) compared with preoperative lip volumes. Secondary outcome measures included postoperative complications. Results: A total of 423 patients were identified who underwent surgical lip augmentation using SMAS. Sixty patients with approximately 5 years or more of postoperative photographs were reviewed for complications. Twenty-six patients had 3-month, 1-year, and 5-year postoperative follow-up photographs and were included in the photographic evaluation. The mean age of these patients at the time of surgery was 54.6 years (range, 41.2-80.6 years. Fifty-nine of the 60 patients (98.3%) were female. Two of 60 patients (3.3%) with 5 years or more of postoperative follow-up developed complications requiring intervention. Both the superior lip and the inferior lip showed statistically significant increases in volume at 3 months, 1 year, and 5 years (P <= .004 for the superior lip after 5 years; P <= .001 for all other comparisons) after SMAS lip augmentation. The greatest median increase was observed in the superior lip at 3 months, while the smallest median increase was observed for the inferior lip at 5 years. The degree of increase in median volume seemed to weaken slightly over time, but remained statistically significant even at 5 years. Conclusions and Relevance: SMAS lip augmentation is an effective and safe method for lip augmentation that can yield natural, long-lasting results with minimal risk. The degree of augmentation tends to fade slightly over time, but remains significant for at least 5 years postoperatively. Level of Evidence: 3. PMID- 27684047 TI - Update on second-trimester surgical abortion. AB - PURPOSE OF REVIEW: To review the recent literature on surgical second-trimester abortion, with specific attention to cervical preparation techniques. RECENT FINDINGS: Confirming previous studies, a recent retrospective observational cohort study, including 54 911 abortions, estimated the total abortion-related complication rate to be 0.41% for second-trimester or later procedures. Cervical preparation is known to reduce risks associated with second-trimester dilation and evacuation (D&E). When considering adjuncts to osmotic dilators for cervical preparation prior to D&E after 16 weeks, both misoprostol and mifepristone are effective alone and in combination or as adjuncts to osmotic dilators. Misoprostol consistently has been shown to cause more pain and cramping than placebo, but is an effective adjunct to osmotic dilators after 16 weeks. Although mifepristone has fewer side-effects, at its current price, it may not be as cost effective as misoprostol. SUMMARY: Second-trimester abortion is safe. The use of mifepristone and misoprostol for second-trimester abortion has improved safety and efficacy of medical and surgical methods when used alone or in combination and as adjuncts to osmotic dilators. An important aspect of D&E, cervical preparation, is not a one-size-fits-all practice; the approach and methods are contingent on patient, provider and setting and should consider all the evidence based options. PMID- 27684046 TI - West Nile virus transmission: results from the integrated surveillance system in Italy, 2008 to 2015. AB - In Italy a national Plan for the surveillance of imported and autochthonous human vector-borne diseases (chikungunya, dengue, Zika virus disease and West Nile virus (WNV) disease) that integrates human and veterinary (animals and vectors) surveillance, is issued and revised annually according with the observed epidemiological changes. Here we describe results of the WNV integrated veterinary and human surveillance systems in Italy from 2008 to 2015. A real time data exchange protocol is in place between the surveillance systems to rapidly identify occurrence of human and animal cases and to define and update the map of affected areas i.e. provinces during the vector activity period from June to October. WNV continues to cause severe illnesses in Italy during every transmission season, albeit cases are sporadic and the epidemiology varies by virus lineage and geographic area. The integration of surveillance activities and a multidisciplinary approach made it possible and have been fundamental in supporting implementation of and/or strengthening preventive measures aimed at reducing the risk of transmission of WNV trough blood, tissues and organ donation and to implementing further measures for vector control. PMID- 27684048 TI - Burkholderia cenocepacia K56-2 trimeric autotransporter adhesin BcaA binds TNFR1 and contributes to induce airway inflammation. AB - Chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). CF pathogens acquire antibiotic resistance, overcome host defenses, and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. Among the multiple CF-associated pathogens, Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria have become prominent contributors of disease progression. Here, we demonstrate that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B. cenocepacia K56-2, is a tumor necrosis factor receptor 1-interacting protein able to regulate components of the tumor necrosis factor signaling pathway and ultimately leading to a significant production of the proinflammatory cytokine IL-8. Notably, this study is the first to demonstrate that a protein belonging to the TAA family is involved in the induction of the inflammatory response during B. cenocepacia infections, contributing to the success of the pathogen. Moreover, our results reinforce the relevance of the TAA BcaA as a multifunctional protein with a major role in B. cenocepacia virulence. PMID- 27684051 TI - Stable Red-Emissive Cationic Dithienotropylium Dyes. AB - A series of thiophene-fused tropylium ions, containing various electron-donating amino groups at the terminal positions, was synthesized. The fusion of the thiophene rings, as well as the presence of the terminal amino groups endows the cationic tropylium ion with excellent stability and high pKR+ values. X-ray crystallographic analysis of these compounds revealed a pronounced quinoidal character for the amino-substituted dithienotropylium skeletons. These compounds exhibit attractive photophysical properties such as strong absorption in the visible region combined with red fluorescence. Theoretical calculations suggested that the 3,3'-bithiophene substructure should be crucial for attaining these photophysical properties. PMID- 27684052 TI - Mitochondria-Targeted Antioxidants and Uncouplers of Oxidative Phosphorylation in Treatment of the Systemic Inflammatory Response Syndrome (SIRS). AB - Systemic inflammatory response syndrome (SIRS) development is accompanied by mitochondrial dysfunction and excessive ROS production. Mitochondrial dysfunctions also occur in many SIRS-related diseases and may be critical for their pathogenesis; therefore, a use of mitochondria-targeted drugs is a promising trend in SIRS research and therapy. Here, we review recent studies concerning the application of the mitochondria-targeted antioxidants and uncouplers of oxidative phosphorylation in animal models of SIRS and related diseases. We propose that a new class of uncouplers of oxidative phosphorylation, lipophilic cations could be a base for a new generation of drugs for SIRS treatment. J. Cell. Physiol. 232: 904-912, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27684050 TI - Effect of feeder free poly(lactide-co-glycolide) scaffolds on morphology, proliferation, and pluripotency of mouse embryonic stem cells. AB - The aim of the study has been to evaluate the morphology, proliferation, and pluripotency maintenance of mouse embryonic stem cells (mESCs) cultivated on poly(lactic-co-glycolic acid) scaffolds. The scaffolds were hydrolyzed with NaOH (treated) and nonhydrolyzed (untreated). Morphological and mechanical characterization of the scaffolds was performed. mESC were evaluated for cell viability, cytotoxicity, expression of pluripotency markers, colony morphology, and overall distribution. The treatment generated a reduction in the hydrophobic characteristics of the scaffolds, leading to a higher wettability compared to the untreated group. The viability, cytotoxicity, number of colonies, and the thickness of the cell layer presented similar results between the scaffold groups. The viability test showed that it was possible to cultivate the mESCs on the scaffolds. The cytotoxicity analysis showed that the PLGA scaffolds were not harmful for the cells. The cells maintained the expression of the pluripotency markers Oct4 and Sox2. The number of colonies and the thickness of the cell layer on the scaffold showed that they were not able to colonize the entire volume of the scaffolds. The area occupied by the mESCs was the same between the treated and untreated groups after 14 days in culture. It is possible to conclude that both conditions are equally suitable for maintaining mESC culture. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 424-432, 2017. PMID- 27684053 TI - Outcomes of Open vs Laparoscopic Rectal Cancer Resection. PMID- 27684049 TI - An orally administered butyrate-releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium-induced murine colitis. AB - BACKGROUND AND PURPOSE: Butyrate has shown benefits in inflammatory bowel diseases. However, it is not often administered orally because of its rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS). EXPERIMENTAL APPROACH: Male 10 week-old BALB/c mice received DSS (2.5%) in drinking water (for 5 days) followed by DSS-free water for 7 days (DSS group). Oral FBA administration (42.5 mg.kg-1 ) was started 7 days before DSS as preventive (P FBA), or 2 days after DSS as therapeutic (T-FBA); both treatments lasted 19 days. One DSS-untreated group received only tap water (CON). KEY RESULTS: FBA treatments reduced colitis symptoms and colon damage. P-FBA and T-FBA significantly decreased polymorphonuclear cell infiltration score compared with the DSS group. FBA reversed the imbalance between pro- and anti-inflammatory cytokines (reducing inducible NOS protein expression, CCL2 and IL-6 transcripts in colon and increasing TGFbeta and IL-10). Morever, P-FBA and T-FBA limited neutrophil recruitment (by expression and localization of the neutrophil granule protease Ly-6G), restored deficiency of the butyrate transporter and improved intestinal epithelial integrity, preventing tight-junction impairment (zonulin-1 and occludin). FBA, similar to its parental compound sodium butyrate, inhibited histone deacetylase-9 and restored H3 histone acetylation, exerting an anti inflammatory effect through NF-kappaB inhibition and the up-regulation of PPARgamma. CONCLUSIONS AND IMPLICATIONS: FBA reduces inflammatory intestinal damage in mice indicating its potential as a postbiotic derivative without the problems associated with the oral administration of sodium butyrate. LINKED ARTICLES: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. PMID- 27684054 TI - High glucose concentration abrogates sevoflurane post-conditioning cardioprotection by advancing mitochondrial fission but dynamin-related protein 1 inhibitor restores these effects. AB - AIM: Hyperglycaemia-induced cell injury is a primary cause of cardiovascular complications in patients with diabetes. In vivo studies demonstrated that sevoflurane post-conditioning (SpostC) was cardioprotective against ischaemia/reperfusion injury, which was blocked by hyperglycaemia. This study investigated whether high glucose concentration abrogated SpostC cardioprotection in vitro by advancing mitochondrial fission and whether mitochondrial division inhibitor-1 (Mdivi-1) restored SpostC cardioprotection in cultured primary neonatal rat cardiomyocytes (NCMs). METHODS: Primary cultured NCMs in low and high glucose concentrations were subjected to hypoxia/reoxygenation (H/R) injury. SpostC was carried out by adding 2.4% sevoflurane to the cells at the beginning of reoxygenation for 15 min. Cell viability, lactate dehydrogenase (LDH) level, cell death, mitochondrial morphology, mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening level, as well as fission- and fusion-related proteins, were measured after H/R injury. Mdivi-1 treatment was performed 40 min before hypoxia to inhibit DRP1. RESULTS: SpostC protected cultured cardiomyocytes by increasing cell viability and reducing the LDH level and cell death following H/R, but high glucose concentration eliminated the cardioprotective effect. High glucose concentration abrogated SpostC cardioprotection via mitochondrial fragmentation (evidenced by decreased mitochondrial interconnectivity and elongation) and facilitation of mPTP opening. Decreased mitochondrial membrane potential was investigated with increased DRP1, FIS1 and MFN2 and decreased MFN1 and OPA1 expressions. Mdivi-1 (100 MUmol L-1 ) inhibited excessive mitochondrial fission and restored the cardioprotective effect of SpostC in high glucose conditions. CONCLUSION: SpostC-induced cardioprotection against H/R injury was impaired under high glucose concentrations, but the inhibition of excess mitochondrial fission restored these effects. PMID- 27684055 TI - Hydroxido-Supported and Carboxylato Bridge-Driven Aggregation for Discrete [Ni4] and Interconnected [Ni2]n Complexes. AB - Four different carboxylato bridges have been efficiently utilized for growth of three tetranuclear nickel(II) complexes [Ni4(MU3-H2L)2(MU3-OH)2(MU1,3 CH3CO2)2](ClO4)2 (1), [Ni4(MU3-H2L)2(MU3-OH)2(MU1,3-C2H5CO2)2](ClO4)2.1/2H2O (2), and [Ni4(MU3-H2L)2(MU3-OH)2(MU1,3-O2C-C6H4-pNO2)2](ClO4)(p-NO2-C6H4-CO2).DMF.5H2O (3) and one dinuclear nickel(II)-based chain complex {[Ni2(MU-H2L)(MU1,3 O2CCH2Ph)2(H2O)](ClO4).1/2(CH3OH)}n (4). These were obtained via the reaction of Ni(ClO4)2.6H2O with H3L [2,6-bis((2-(2-hydroxyethylamino)ethylimino)methyl)-4 methylphenol] and RCO2Na (R = CH3,C2H5, p-NO2C6H4, and PhCH2). This family of complexes is developed from {Ni2(MU-H2L)}3+ fragments following self-aggregation. The complexes were characterized by X-ray crystallography and magnetic measurements. The changes from acetate, propionate, and p-nitrobenzoate to phenylacetate groups resulted in two different types of coordination aggregation. These compounds are new examples of [Ni4] and [Ni2]n complexes where organization of the building motifs are guided by the type of the carboxylate groups responsible for in-situ generation and utilization of HO- bridges with alteration in the aggregation process within the same ligand environment. Studies on the magnetic behavior of the compounds reveal that the exchange coupling within 1-4 is predominantly antiferromagnetic in nature. PMID- 27684056 TI - Successful strategy to treat a solitary cystic melanoma brain metastasis. PMID- 27684057 TI - Proteomic Profiling Reveals the Induction of UPR in Addition to DNA Damage Response in HeLa Cells Treated With the Thiazolo[5,4-b]Quinoline Derivative D3ClP. AB - 9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinolone (D3ClP) is a bioisostere of N-(4-(acridin-9-ylamino)-3 methoxyphenyl)methanesulfonamide (m-AMSA) a DNA topoisomerase II inhibitor with proven cytotoxic activity and known to induce DNA damage and apoptotic cell death in K562 cells. However, recent evidence is not consistent with DNA topoisomerase II (DNA TOP2) as the primary target of D3ClP, in contrast to m-AMSA. We provide evidence of histone gammaH2AX phosphorylation at Ser135 in HeLa cells treated with D3ClP, a marker of DNA double strand repair through Mre11-Rad50-Nbs1 (MRN) pathway. Using two-dimensional gel electrophoresis and mass spectrometry, the upregulation of the protein GRP78, the cleavage of Cytokeratin 18, and the downregulation of prothymosine, calumenin, and the alpha chain of the nascent polypeptide associated complex were observed in HeLa cells treated with D3ClP. An increase in GRP78 has been related with the onset and progression of the unfolded protein response (UPR), a process aimed to reduce endoplasmic reticulum (ER) stress and protein misfolding. The IRE1-alpha dependent splicing of mRNA encoding X-box binding protein 1 was detected. Microtubule-associated Proteins 1A/1B, Light Chain 3-II (LC3b-II) accumulation was observed, and suggest some involvement of autophagy. The production of the pro-apoptotic protein DNA-damage inducible protein 153 (GADD-153) was also detected. These results, are consistent with the induction of the UPR and the DNA-Damage Response in D3ClP-treated HeLa cells, and are also consistent with a concurrent apoptotic cell death. J. Cell. Biochem. 118: 1164-1173, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27684058 TI - Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis. AB - Pseudoarthrosis is a relatively frequent complication of fractures, in which the lack of mechanical stability and biological stimuli results in the failure of bone union, most frequently in humerus and tibia. Treatment of recalcitrant pseudoarthrosis relies on the achievement of satisfactory mechanical stability combined with adequate local biology. Herein we present two cases of atrophic pseudoarthrosis that received a tissue-engineering product (TEP) composed of autologous bone marrow-derived mesenchymal stromal cells (BM-MSC) combined with deantigenized trabecular bone particles from a tissue bank. The feasibility of the treatment and osteogenic potential of the cell-based medicine was first demonstrated in an ovine model of critical size segmental tibial defect. Clinical grade autologous BM-MSC were produced following a good manufacturing practice compliant bioprocess. Results were successful in one case, with pseudoarthrosis resolution, and inconclusive in the other one. The first patient presented atrophic pseudoarthrosis of the humeral diaphysis and was treated with osteosynthesis and TEP resulting in satisfactory consolidation at month 6. The second case presented a recalcitrant pseudoarthrosis of the proximal tibia and the Masquelet technique was followed before filling the defect with the TEP. This patient presented a neuropathic pain syndrome unrelated to the treatment that forced the amputation of the extremity 3 months later. In this case, the histological analysis of the tissue formed at the defect site provided evidence of neovascularization but no overt bone remodelling activity. It is concluded that the use of expanded autologous BM-MSC to treat pseudoarthrosis was demonstrated to be feasible and safe, provided that no clinical complications were reported, and early signs of effectiveness were observed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27684059 TI - Arthroscopy of the Dorsal and Plantar Pouches of the Tarsocrural Joint for the Treatment of Osteochondritis Dissecans in the Horse: Clinical Features and Follow Up. AB - OBJECTIVE: To describe the clinical details and pathology within the dorsal and plantar pouches of the tarsocrural joint of a population of horses that underwent arthroscopic surgery for tarsocrural osteochondritis dissecans (OCD). STUDY DESIGN: Retrospective cohort study. ANIMALS: Horses referred for arthroscopic treatment of tarsocrural OCD between 2005 and 2013 (102 horses; 144 joints). METHODS: Case records of all horses that had tarsocrural arthroscopy for OCD at Rossdales Equine Hospital, Newmarket, United Kingdom were included. Cases from 3 ECVS Diplomates were included, 1 of whom routinely examined 70 plantar pouches concurrently with routine dorsal pouch investigation. A structured questionnaire was used to obtain follow-up data alongside examination of racing records where appropriate. Descriptive data and 95% CI were calculated. RESULTS: Of the 70 joints that had both dorsal and plantar pouches examined, there was cartilage erosion/degeneration in 22 dorsal pouches (31.4%), cartilage wear lines in 32 plantar pouches (45.7%), and fragments were removed at the time of surgery from 7 plantar pouches (10.0%). Of the plantar pouches with wear lines, 18 (25.7%) had no evidence of cartilage abnormalities (separate from the OCD lesion) within the dorsal pouch. From the 102 horses with available follow-up, 34 horses (66.7%) achieved their intended use postsurgery. CONCLUSION: Routine plantar pouch investigation is warranted in cases of tarsocrural OCD to provide further information on the health of the joint and allows for removal of fragments from the plantar pouch that may not have been identified by routine diagnostic radiography. PMID- 27684060 TI - Boldness, Aggression, and Shoaling Assays for Zebrafish Behavioral Syndromes. AB - A behavioral syndrome exists when specific behaviors interact under different contexts. Zebrafish have been test subjects in recent studies and it is important to standardize protocols to ensure proper analyses and interpretations. In our previous studies, we have measured boldness by monitoring a series of behaviors (time near surface, latency in transitions, number of transitions, and darts) in a 1.5 L trapezoidal tank. Likewise, we quantified aggression by observing bites, lateral displays, darts, and time near an inclined mirror in a rectangular 19 L tank. By dividing a 76 L tank into thirds, we also examined shoaling preferences. The shoaling assay is a highly customizable assay and can be tailored for specific hypotheses. However, protocols for this assay also must be standardized, yet flexible enough for customization. In previous studies, end chambers were either empty, contained 5 or 10 zebrafish, or 5 pearl danios (D. albolineatus). In the following manuscript, we present a detailed protocol and representative data that accompany successful applications of the protocol, which will allow for replication of behavioral syndrome experiments. PMID- 27684061 TI - Influence of the State of the Subarachnoid Space of the Cranial Base in Hydrocephalus Resolution after Endoscopy. AB - Objective To compare the resolution rate of hydrocephalus after endoscopy (predominantly endoscopic third ventriculostomy [ETV]) using flexible endoscopes during a 5-year period in patients with a permeable and a nonpermeable subarachnoid space (SAS). Material and Methods We conducted a retrospective cohort study of the videos and records of 150 hydrocephalic patients chosen randomly who underwent ETV (and other endoscopic procedures) with a flexible endoscope. The patients were classified into two groups based on the neuroendoscopic findings. The first group included patients with a permeable SAS, and the second group included patients with a nonpermeable SAS. A normal SAS or one with slight arachnoiditis was considered permeable. Adhesive arachnoiditis and immature or mechanically obliterated SASs were considered nonpermeable. Results We found a success rate of 70% in patients with a permeable SAS versus 33% in patients with a nonpermeable SAS. The baseline characteristics of both groups were homogeneous. We obtained a statistically significant difference (p < 0.0001) with hazard ratio (HR) 3.42 (95% confidence interval [CI], 1.88-6.22). Another important factor involved was age that showed a statistically significant difference (p < 0.0018) with HR 3.28 (95% CI, 1.55-6.93). Conclusion The permeability of the SAS is an important prognostic factor in the resolution rate of hydrocephalus after ETV (and other endoscopic procedures) using flexible neuroendoscopes. Therefore we recommend that the characteristics of the SAS be examined following every endoscopic procedure for hydrocephalus to identify patients at risk of recurrence. PMID- 27684062 TI - Genotyping Oral Commensal Bacteria to Predict Social Contact and Structure. AB - Social network structure is a fundamental determinant of human health, from infectious to chronic diseases. However, quantitative and unbiased approaches to measuring social network structure are lacking. We hypothesized that genetic relatedness of oral commensal bacteria could be used to infer social contact between humans, just as genetic relatedness of pathogens can be used to determine transmission chains of pathogens. We used a traditional, questionnaire survey based method to characterize the contact network of the School of Public Health at a large research university. We then collected saliva from a subset of individuals to analyze their oral microflora using a modified deep sequencing multilocus sequence typing (MLST) procedure. We examined micro-evolutionary changes in the S. viridans group to uncover transmission patterns reflecting social network structure. We amplified seven housekeeping gene loci from the Streptococcus viridans group, a group of ubiquitous commensal bacteria, and sequenced the PCR products using next-generation sequencing. By comparing the generated S. viridans reads between pairs of individuals, we reconstructed the social network of the sampled individuals and compared it to the network derived from the questionnaire survey-based method. The genetic relatedness significantly (p-value < 0.001) correlated with social distance in the questionnaire-based network, and the reconstructed network closely matched the network derived from the questionnaire survey-based method. Oral commensal bacterial are thus likely transmitted through routine physical contact or shared environment. Their genetic relatedness can be used to represent a combination of social contact and shared physical space, therefore reconstructing networks of contact. This study provides the first step in developing a method to measure direct social contact based on commensal organism genotyping, potentially capable of unmasking hidden social networks that contribute to pathogen transmission. PMID- 27684063 TI - Pulsed Light Stimulation Increases Boundary Preference and Periodicity of Episodic Motor Activity in Drosophila melanogaster. AB - There is considerable interest in the therapeutic benefits of long-term sensory stimulation for improving cognitive abilities and motor performance of stroke patients. The rationale is that such stimulation would activate mechanisms of neural plasticity to promote enhanced coordination and associated circuit functions. Experimental approaches to characterize such mechanisms are needed. Drosophila melanogaster is one of the most attractive model organisms to investigate neural mechanisms responsible for stimulation-induced behaviors with its powerful accessibility to genetic analysis. In this study, the effect of chronic sensory stimulation (pulsed light stimulation) on motor activity in w1118 flies was investigated. Flies were exposed to a chronic pulsed light stimulation protocol prior to testing their performance in a standard locomotion assay. Flies responded to pulsed light stimulation with increased boundary preference and travel distance in a circular arena. In addition, pulsed light stimulation increased the power of extracellular electrical activity, leading to the enhancement of periodic electrical activity which was associated with a centrally generated motor pattern (struggling behavior). In contrast, such periodic events were largely missing in w1118 flies without pulsed light treatment. These data suggest that the sensory stimulation induced a response in motor activity associated with the modifications of electrical activity in the central nervous system (CNS). Finally, without pulsed light treatment, the wild-type genetic background was associated with the occurrence of the periodic activity in wild type Canton S (CS) flies, and w+ modulated the consistency of periodicity. We conclude that pulsed light stimulation modifies behavioral and electrophysiological activities in w1118 flies. These data provide a foundation for future research on the genetic mechanisms of neural plasticity underlying such behavioral modification. PMID- 27684066 TI - Household Knowledge of Antimicrobials and Antimicrobial Resistance in the Wake of an Accredited Drug Dispensing Outlet (ADDO) Program Rollout in Tanzania. AB - INTRODUCTION: Private sector drug shops are an important source of medicines in Tanzania. In 2003, the government introduced the accredited drug dispensing outlet (ADDO) program to improve access to good-quality medicines in rural and peri-urban areas that have frequent drug shortages in public health facilities and few or no registered pharmacies. However, increasing access may also contribute to antimicrobial resistance (AMR) due to the potential overuse and misuse of drugs. METHODS: We conducted a cross-sectional household survey in four regions in mainland Tanzaniato characterize consumer care-seeking habits and medicines use and to determine the extent to which members of the community are knowledgeable about antimicrobials and AMR. Within the regions, we applied a multistage cluster sampling design, cascading from districts, wards, and villages to households. Multivariate logistic analysis was done to determine variables influencing knowledge of antimicrobials and AMR, while controlling for confounding factors. Variables included age, occupation, level of education, membership in an insurance scheme, and wealth status. RESULTS AND DISCUSSION: We revealed that communities in four Tanzanian regions have low levels of knowledge of the concepts of antimicrobials and their use and AMR. Level of public understanding rose with wealth status and education. Only one-third of 1,200 respondents (33.6%) had ever heard of a medicine called an antimicrobial, and 5 15% could name at least one antimicrobial spontaneously. Some thought other medicines, such as paracetamol were antimicrobial (7.5%). People were equally likely to agree that pneumonia should be treated with an antimicrobial (21.4%) as well as common cold (28.4%). Understanding of AMR risks was better, particularly related to HIV and AIDS (32.2%) and malaria (38.6%)-most likely due to information campaigns focused on those two diseases. The level of knowledge decreased the further away respondents lived from an ADDO (p = 0.0001) and where ADDO density was lower (p = 0.001), which supports the use of ADDO dispensers as sources of community information and change agents for more appropriate medicine use. CONCLUSION: Lack of knowledge about antimicrobials and AMR in Tanzanian communities needs to be addressed through multi-pronged strategies that focus on prescribers and the public-especially those who are poorer and less educated. PMID- 27684065 TI - The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis. AB - Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group. We determined total and differential leukocyte count, erythrocyte sedimentation rate and plasma abundance of cytokines and chemokines as markers for systemic inflammation and scored chest X-rays to assess lung involvement in TB subjects. Most disease parameters segregated independently of the CARD9 haplotypes. In contrast to multifactorial chronic inflammation, selected genetic variants in the CARD9 gene leave host responses apparently unaffected in TB, at least in the population analyzed here. PMID- 27684067 TI - The Relationship between Behavioural Changes, Cognitive Symptoms, and Functional Disability in Primary Progressive Aphasia: A Longitudinal Study. AB - BACKGROUND: The contribution of behavioural changes to functional decline is yet to be explored in primary progressive aphasia (PPA). OBJECTIVES: (1) investigate functional changes in two PPA variants [semantic (svPPA) and non-fluent (nfvPPA)], at baseline and after 12 months; (2) investigate baseline differences in behavioural changes between groups, and (3) explore predictors of functional decline after a 12-month period. METHODS: A longitudinal study involving 29 people with PPA (18 svPPA; 11 nfvPPA) seen annually in Sydney/Australia was conducted. A total of 114 functional and behavioural assessments were included for within-group (repeated-measures ANOVA; annual rate of change; multiple regression analyses) and between-group analyses (pairwise comparisons). RESULTS: Functional profiles in svPPA and nfvPPA were similar in people with up to 5 years of disease duration. Behavioural changes were marked in svPPA patients (stereotypical behaviour and apathy) but did not predict annual rate of change of functional abilities; global cognitive scores at baseline did. Despite mild behavioural changes in nfvPPA (disinhibition, apathy), these were significant predictors of annual rate of functional change. CONCLUSIONS: The presentation and interplay of behavioural changes and functional disability differ in svPPA and nfvPPA. These varying factors should be taken into account when considering prognosis, disease management, and selection of outcome measures for interventions. PMID- 27684064 TI - Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. AB - Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse. PMID- 27684070 TI - Morphological Characterization of Papillary Renal Cell Carcinoma Type 1, the Efficiency of Its Surgical Treatment. AB - AIM: Papillary renal cell carcinoma type 1 (pRCC1) represents the second most common type of malignant renal epithelial tumour. The origin of its characteristic appearance, its growth mechanism, and the long-term efficiency of its surgical treatment remain uncertain. Our aim was to determine typical characteristics of surgically treated pRCC1. METHODS: pRCC1 was verified in 83 of 1,629 (5.1%) kidney tumours surgically treated in the period of January 2007 January 2016. The clinical and radiological characteristics, type of surgery, histopathology results and follow up data were recorded. Spearman correlation, Kruskal-Wallis analysis of variance, Fisher's exact, and chi-square test were used to analyse appropriate variables. The overall survival rate was evaluated using the Gehan-Wilcoxon test and the Cox proportional hazards model. RESULTS: The mean tumour size was 52.0 mm (15-180); 98.8% of the tumours showed a spherical shape and in 82.1%, exophytic growth was observed. Partial nephrectomy was performed in 80.7%. A majority (81.9%) were classified as pT1. Tumours, 89.2% of them, belonged to Fuhrman grade 1 or 2. The mean follow-up was 46.8 months. The overall survival was associated with pT category (p <= 0.0001). CONCLUSIONS: Typical signs of pRCC1 are a spherical shape, exophytic growth and low Fuhrman's grade. More than three-fourths of pRCC1 could be treated by the nephron-sparing surgery. PMID- 27684068 TI - Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues. AB - OBJECTIVE: IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. METHODS: Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. RESULTS: Our results show that IL 15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro inflammatory mediators in their adipose tissues. CONCLUSIONS: Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome. PMID- 27684069 TI - Microscale In Vitro Assays for the Investigation of Neutral Red Retention and Ethoxyresorufin-O-Deethylase of Biofuels and Fossil Fuels. AB - Only few information on the potential toxic effectiveness of biofuels are available. Due to increasing worldwide demand for energy and fuels during the past decades, biofuels are considered as a promising alternative for fossil fuels in the transport sector. Hence, more information on their hazard potentials are required to understand the toxicological impact of biofuels on the environment. In the German Cluster of Excellence "Tailor-made Fuels from Biomass" design processes for economical, sustainable and environmentally friendly biofuels are investigated. In an unique and interdisciplinary approach, ecotoxicological methods are applied to gain information on potential adverse environmental effects of biofuels at an early phase of their development. In the present study, three potential biofuels, ethyl levulinate, 2-methyltetrahydrofuran and 2 methylfuran were tested. Furthermore, we investigated a fossil gasoline fuel, a fossil diesel fuel and an established biodiesel. Two in vitro bioassays, one for assessing cytotoxicity and one for aryl hydrocarbon receptor agonism, so called dioxin-like activity, as measured by Ethoxyresorufin-O-Deethylase, were applied using the permanent fish liver cell line RTL-W1 (Oncorhynchus mykiss). The special properties of these fuel samples required modifications of the test design. Points that had to be addressed were high substance volatility, material compatibility and low solubility. For testing of gasoline, diesel and biodiesel, water accommodated fractions and a passive dosing approach were tested to address the high hydrophobicity and low solubility of these complex mixtures. Further work has to focus on an improvement of the chemical analyses of the fuel samples to allow a better comparison of any effects of fossil fuels and biofuels. PMID- 27684071 TI - Arterio-Venous Fistula: Is it Critical for Prolonged Survival in the over 80's Starting Haemodialysis? AB - BACKGROUND: Dialysis in elderly patients (>80-years-old) carries a poor prognosis, but little is known about the most effective vascular access method in this age group. An arteriovenous fistula (AVF) is both time-consuming and initially expensive, requiring surgical insertion. A central venous catheter (CVC) is initially a cheaper alternative, but carries a higher risk of infection. We examined whether vascular access affected 1-year and 2-year mortality in elderly patients commencing haemodialysis. METHODS: Initial vascular access, demographic and survival data for elective haemodialysis patients >80-years was collated using regional databases. A cohort of conservatively managed patients was included for comparison. A log-rank test was used to compare survival between groups and a chi-square test was used to compare 1-year and 2-year survival. RESULTS: 167 patients (61% male) were included: CVC (101), AVF (25) and conservative management (41). Mean age (median) of starting haemodialysis (eGFR <=10mL/min/1.73m2): CVC; 83.4 (2.3) and AVF; 82.3 (1.8). Mean age of conservatively managed patients reaching an eGFR <=10mL/min/1.73m2 was 85.8 (3.6). Mean (median) survival on dialysis was 2.2 (1.8) years for AVF patients, 2.1 (1.2) for CVC patients, and 1.5 (0.9) for conservatively managed patients (p = 0.107, controlling for age/sex p = 0.519). 1-year and 2-year mortality: AVF (28%/52%); CVC (49%/57%), and conservative management (54%/68%). There was no significant difference between the groups at 1-year (p = 0.108) or 2-years (p = 0.355). CONCLUSION: These results suggest that there is no significant survival benefit over a 2-year period when comparing vascular access methods. In comparison to conservative management, survival benefit was marginal. The decision of whether and how (choice of their vascular access method) to dialysis the over 80s is multifaceted and requires a tailored, multidisciplinary approach. PMID- 27684072 TI - Tenure Track Policy Increases Representation of Women in Senior Academic Positions, but Is Insufficient to Achieve Gender Balance. AB - Underrepresentation of women in senior positions is a persistent problem in universities worldwide, and a wide range of strategies to combat this situation is currently being contemplated. One such strategy is the introduction of a tenure track system, in which decisions to promote scientific staff to higher ranks are guided by a set of explicit and transparent criteria, as opposed to earlier situations in which decisions were based on presumably more subjective impressions by superiors. We examined the effect of the introduction of a tenure track system at Wageningen University (The Netherlands) on male and female promotion rates. We found that chances on being promoted to higher levels were already fairly equal between men and women before the tenure track system was introduced, and improved-more for women than for men-after the introduction of the tenure track system. These results may partly be explained by affirmative actions, but also by the fact that legacy effects of historical discrimination have led to a more competitive female population of scientists. In spite of these outcomes, extrapolations of current promotion rates up to 2025 demonstrate that the equal or even higher female promotion rates do not lead to substantial improvement of the gender balance at higher levels (i.e., associate professor and higher). Since promotion rates are small compared to the total amount of staff, the current distribution of men and women will, especially at higher levels, exhibit a considerable degree of inertia-unless additional affirmative action is taken. PMID- 27684075 TI - Relative Importance of Climate Variables to Population Vital Rates: A Quantitative Synthesis for the Lesser Prairie-Chicken. AB - Climate change is expected to affect temperature and precipitation means and extremes, which can affect population vital rates. With the added complexity of accounting for both means and extremes, it is important to understand whether one aspect is sufficient to predict a particular vital rate or if both are necessary. To compare the predictive ability of climate means and extremes with geographic, individual, and habitat variables, we performed a quantitative synthesis on the vital rates of lesser prairie-chickens (Tympanuchus pallidictinus) across their geographic range. We used an information theoretic approach to rank models predicting vital rates. We were able to rank climate models for three vital rates: clutch size, nest success, and subadult/adult seasonal survival. Of these three vital rates, a climate model was never the best predictor even when accounting for potentially different relationships between climate variables and vital rates between different ecoregions. Clutch size and nest success were both influenced by nesting attempt with larger clutches and greater success for first nesting attempts than second nesting attempts. Clutch size also increased with latitude for first nesting attempts but decreased with latitude for second nesting attempts. This resulted in similar clutch sizes for first and second nest attempts at southern latitudes but larger clutches for first nest attempts than second nest attempts at northern latitudes. Survival was greater for subadults than adults, but there were few estimates of subadult survival for comparison. Our results show that individual characteristics and geographic variables are better for predicting vital rates than climate variables. This may due to low samples sizes, which restricted our statistical power, or lack of precision in climate estimates relative to microclimates actually experienced by individuals. Alternatively, relationships between climate variables and vital rates may be constrained by time lags or local adaptation. PMID- 27684074 TI - Toward achieving harmonization in a nano-cytotoxicity assay measurement through an interlaboratory comparison study. AB - Development of reliable cell-based nanotoxicology assays is important for evaluation of potentially hazardous engineered nanomaterials. Challenges to producing a reliable assay protocol include working with nanoparticle dispersions and living cell lines, and the potential for nano-related interference effects. Here we demonstrate the use of a 96-well plate design with several measurement controls and an interlaboratory comparison study involving five laboratories to characterize the robustness of a nanocytotoxicity MTS cell viability assay based on the A549 cell line. The consensus EC50 values were 22.1 mg/L (95% confidence intervals 16.9 mg/L to 27.2 mg/L) and 52.6 mg/L (44.1 mg/L to 62.6 mg/L) for positively charged polystyrene nanoparticles for the serum-free and serum conditions, respectively, and 49.7 MUmol/L (47.5 MUmol/L to 51.5 MUmol/L) and 77.0 MUmol/L (54.3 MUmol/L to 99.4 MUmol/L) for positive chemical control cadmium sulfate for the serum-free and serum conditions, respectively. Results from the measurement controls can be used to evaluate the sources of variability and their relative magnitudes within and between laboratories. This information revealed steps of the protocol that may need to be modified to improve the overall robustness and precision. The results suggest that protocol details such as cell line ID, media exchange, cell handling, and nanoparticle dispersion are critical to ensure protocol robustness and comparability of nanocytotoxicity assay results. The combination of system control measurements and interlaboratory comparison data yielded insights that would not have been available by either approach by itself. PMID- 27684076 TI - Experimental Study of a Reference Model Vertical-Axis Cross-Flow Turbine. AB - The mechanical power, total rotor drag, and near-wake velocity of a 1:6 scale model (1.075 m diameter) of the US Department of Energy's Reference Model vertical-axis cross-flow turbine were measured experimentally in a towing tank, to provide a comprehensive open dataset for validating numerical models. Performance was measured for a range of tip speed ratios and at multiple Reynolds numbers by varying the rotor's angular velocity and tow carriage speed, respectively. A peak power coefficient CP = 0.37 and rotor drag coefficient CD = 0.84 were observed at a tip speed ratio lambda0 = 3.1. A regime of weak linear Re dependence of the power coefficient was observed above a turbine diameter Reynolds number ReD ~ 106. The effects of support strut drag on turbine performance were investigated by covering the rotor's NACA 0021 struts with cylinders. As expected, this modification drastically reduced the rotor power coefficient. Strut drag losses were also measured for the NACA 0021 and cylindrical configurations with the rotor blades removed. For lambda = lambda0, wake velocity was measured at 1 m (x/D = 0.93) downstream. Mean velocity, turbulence kinetic energy, and mean kinetic energy transport were compared with results from a high solidity turbine acquired with the same test apparatus. Like the high solidity case, mean vertical advection was calculated to be the largest contributor to near-wake recovery. However, overall, lower levels of streamwise wake recovery were calculated for the RM2 case-a consequence of both the relatively low solidity and tapered blades reducing blade tip vortex shedding responsible for mean vertical advection-and lower levels of turbulence caused by higher operating tip speed ratio and therefore reduced dynamic stall. Datasets, code for processing and visualization, and a CAD model of the turbine have been made publicly available. PMID- 27684073 TI - Quantitative imaging reveals real-time Pou5f3-Nanog complexes driving dorsoventral mesendoderm patterning in zebrafish. AB - Formation of the three embryonic germ layers is a fundamental developmental process that initiates differentiation. How the zebrafish pluripotency factor Pou5f3 (homologous to mammalian Oct4) drives lineage commitment is unclear. Here, we introduce fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy to assess the formation of Pou5f3 complexes with other transcription factors in real-time in gastrulating zebrafish embryos. We show, at single-cell resolution in vivo, that Pou5f3 complexes with Nanog to pattern mesendoderm differentiation at the blastula stage. Later, during gastrulation, Sox32 restricts Pou5f3-Nanog complexes to the ventrolateral mesendoderm by binding Pou5f3 or Nanog in prospective dorsal endoderm. In the ventrolateral endoderm, the Elabela / Aplnr pathway limits Sox32 levels, allowing the formation of Pou5f3-Nanog complexes and the activation of downstream BMP signaling. This quantitative model shows that a balance in the spatiotemporal distribution of Pou5f3-Nanog complexes, modulated by Sox32, regulates mesendoderm specification along the dorsoventral axis. PMID- 27684077 TI - The Prognostic Role of the Platelet-Lymphocytes Ratio in Gastric Cancer: A Meta Analysis. AB - BACKGROUND: Systemic inflammatory parameters, such as the elevator PLR (platelet lymphocyte ratio), the NLR (neutrophil-lymphocyte ratio) and the platelet count (PLT), have been found to be associated with the prognosis in gastric cancer; however, these results, especially those relating to the PLR, remain inconsistent. So we aimed to evaluate the prognostic role of the PLR in gastric cancer by conducting and presenting the findings of this meta-analysis. METHODS: We conducted a systematic literature search in PubMed, Embase and the Cochrane Library to evaluate the prognostic value of the PLR in gastric cancer. The quality of the included studies was evaluated using the Newcastle Ottawa Quality Assessment Scale (NOS). The hazard ratio (HR) /Odds Ratio (OR) and its 95% confidence were pooled using a random effects model. A funnel plot based on overall survival was used to evaluate the publication bias. RESULTS: It total, 8 studies comprising 4513 patients with gastric cancer met the pre-setting inclusion criteria. In comparison to the normal PLR, an elevated PLR was correlated with a higher risk of lymph node metastasis with an OR of 1.50 (95% Cl:1.24-1.82; I2 = 17%) and serosal invasion (T3 +T4) risk with an OR of 2.01 (95% Cl: 1.49-2.73; I2 = 55%), and an elevated PLR also increased the advanced stage (III +IV) risk with an OR of 1.99 (95% Cl: 1.60-2.46; I2 = 28%). An elevated PLR was not a reliable predictor for OS with an HR of 0.99 (95% CI: 0.9 1.1; I2 = 12%). CONCLUSIONS: An elevated PLR was correlated with a higher risk of lymph node metastasis, serosal invasion and advanced stage (III +IV) risk in gastric cancer; however, the PLR may not act as a negative predictor for the overall survival of gastric cancer. PMID- 27684078 TI - Treatment of Massive Irreparable Rotator Cuff Tears: A Cost-effectiveness Analysis. AB - Massive irreparable rotator cuff tears cause significant shoulder pain and dysfunction. Physical therapy (PT), arthroscopic debridement with biceps tenotomy (AD-BT), and hemiarthroplasty (HA) are treatments shown to reduce pain and improve quality of life. Reverse total shoulder arthroplasty (RTSA) is a newer surgical treatment option that may offer improved function. A cost-effectiveness analysis of these interventions has never been performed, and no head-to-head comparative effectiveness trials currently exist. A Markov decision analytic model was used to compare RTSA, HA, AD-BT, and PT as treatments for elderly patients with massive irreparable rotator cuff tears. Probabilities for complications, perioperative death, conversion procedures, and reoperations were derived from the literature, and costs were determined by average Medicare reimbursement rates from 2011. Reverse total shoulder arthroplasty yielded the most quality-adjusted life years (QALY) with 7.69, but greater benefits came at higher costs compared with other treatments. Sensitivity analyses showed that PT was the most cost-effective intervention at a health utility of 0.75 or greater (QALY 7.35). The health utility of RTSA was 0.72 or less (QALY 7.48) or RTSA probability of no complications was 0.83 or less (QALY 7.48 at cost of $23,830). Reverse total shoulder arthroplasty yielded benefits at a cost considered good value for money compared with other treatments. Reverse total shoulder arthroplasty is the preferred and most cost-effective treatment option for elderly patients with massive irreparable rotator cuff tears. For patients seeking pain relief without functional gains, AD-BT can be considered a cost effective and cheaper alternative. The cost-effectiveness analysis approach can help guide clinical practice as well as the policies of health care systems and insurers. [Orthopedics. 2017; 40(1):e65-e76.]. PMID- 27684079 TI - Treatment of Atypical Compartment Syndrome Due to Proteus Infection. AB - Compartment syndrome is an orthopedic emergency with a multitude of etiologies. Although it is most commonly associated with trauma to the extremity, hematoma and infection are 2 rare etiologies of insidious compartment syndrome. Proteus mirabilis is an opportunistic gram-negative species that can infect the respiratory tract, urinary tract, and open wounds. The authors present the case of a 69-year-old woman who developed tissue necrosis and compartment syndrome secondary to an untreated hematoma infected by P mirabilis. This case involves an atypical presentation caused by an untreated infected hematoma, emphasizing the need for a high index of suspicion. Current literature supports immediate surgical intervention in the clinical scenario of fulminant compartment syndrome, regardless of compartment pressure findings. The probability of compartment syndrome in the patient presenting with pain, paresthesias, paresis, and pain with passive stretch, all of which were positive findings in this patient, has been reported to be 98%. Thus, Doppler evaluation and intercompartmental pressures were considered but forgone to expedite operative treatment. Emergent 4 compartment fasciotomies, with excision and debridement of nonviable tissue, are potentially limb-saving procedures, intended to limit loss of function and obviate the need for lower extremity amputation. The decision was made to perform a dual-incision fasciotomy to avoid contamination of the uninvolved compartments with a standard single-incision approach. To date, this represents the first report in the English literature of the insidious onset of tissue necrosis secondary to a Proteus-infected hematoma, highlighting a unique etiology of atypical compartment syndrome. [Orthopedics. 2017; 40(1):e176-e178.]. PMID- 27684080 TI - Acquired Upper Extremity Growth Arrest. AB - This study reviewed the clinical history and management of acquired growth arrest in the upper extremity in pediatric patients. The records of all patients presenting from 1996 to 2012 with radiographically proven acquired growth arrest were reviewed. Records were examined to determine the etiology and site of growth arrest, management, and complications. Patients with tumors or hereditary etiology were excluded. A total of 44 patients (24 boys and 20 girls) with 51 physeal arrests who presented at a mean age of 10.6 years (range, 0.8-18.2 years) were included in the study. The distal radius was the most common site (n=24), followed by the distal humerus (n=8), metacarpal (n=6), distal ulna (n=5), proximal humerus (n=4), radial head (n=3), and olecranon (n=1). Growth arrest was secondary to trauma (n=22), infection (n=11), idiopathy (n=6), inflammation (n=2), compartment syndrome (n=2), and avascular necrosis (n=1). Twenty-six patients (59%) underwent surgical intervention to address deformity caused by the physeal arrest. Operative procedures included ipsilateral unaffected bone epiphysiodesis (n=21), shortening osteotomy (n=10), lengthening osteotomy (n=8), excision of physeal bar or bone fragment (n=2), angular correction osteotomy (n=1), and creation of single bone forearm (n=1). Four complications occurred; 3 of these required additional procedures. Acquired upper extremity growth arrest usually is caused by trauma or infection, and the most frequent site is the distal radius. Growth disturbances due to premature arrest can be treated effectively with epiphysiodesis or osteotomy. In this series, the specific site of anatomic growth arrest was the primary factor in determining treatment. [Orthopedics. 2017; 40(1):e95-e103.]. PMID- 27684081 TI - Effects of Tumor Necrosis Factor Inhibitor on Stress-Shielded Tendons. AB - Mechanical stress plays an important role in preserving the integrity of bone and ligament. Stress shielding reduces mechanical load on bone or tendons, resulting in tissue degradation. Previous studies showed that deterioration of the tendon structure during stress shielding is associated with elevated expression of tumor necrosis factor (TNF)-alpha. This study examined the therapeutic potential of the TNF inhibitor etanercept in preventing morphologic deterioration of the Achilles tendon after stress shielding. Rats (N=48) were exposed to stress shielding of the left Achilles tendon and treated with etanercept or phosphate-buffered saline for 2 or 4 weeks. The right Achilles tendons were used as controls. After 2 or 4 weeks, stress-shielded tendons appeared less smooth than control tendons, and the stress-shielded tendons formed adhesions with surrounding tissues. Transmission electron microscopy also showed disarray of the collagen fibrils and a significant increase in the number of small-diameter collagen fibrils. These changes were associated with increased expression of TNF-alpha, matrix metalloproteinase (MMP)-13, MMP-3, collagen I, and collagen III. Treatment with 2 weeks of etanercept injection reduced morphologic changes in collagen organization and structure induced by stress shielding. Etanercept treatment also attenuated upregulation of MMP-13, MMP-3, and collagen III levels. However, no significant difference was observed between the etanercept group and the phosphate-buffered saline group after 4 weeks of treatment. The current findings show that TNF-alpha inhibition can protect against the early stages of tendon tissue remodeling induced by stress shielding, but additional interventions may be necessary to prevent tendon degeneration with long-term stress shielding. [Orthopedics. 2017; 40(1):49-55.]. PMID- 27684082 TI - Intraobserver Reliability and Interobserver Agreement in Radiographic Classification of Heterotopic Ossification. AB - The most widely used radiologic classification system for heterotopic ossification after total hip arthroplasty (THA) is the Brooker scale. In 2002, Della Valle et al proposed a modified rating system for heterotopic ossification to increase intraobserver reliability and interobserver agreement. To date, no study comparing these 2 classification systems has been conducted. Moreover, these studies were grossly underpowered. In the current study, 3 clinicians reviewed the charts of 236 patients with documented radiographic heterotopic ossification at least 2 months after THA and independently graded the amount of heterotopic ossification according to the Brooker and Della Valle classification systems. Then the intraobserver reliability and the interobserver agreement of each classification system were calculated with Cohen's kappa (kappa) coefficient of agreement. The Brooker scale showed moderate to substantial intraobserver reliability (0.43<=kappa<0.71), and the Della Valle classification system showed substantial intraobserver reliability (0.65<=kappa<0.77). Both classification systems showed moderate interobserver agreement (0.40<=kappa<0.60). Della Valle grade C (ie, presence of bone spurs from the pelvis or femur leaving less than 1 cm between opposing surfaces and apparent bone ankylosis) and Brooker grade IV had the best interobserver agreement. The best interobserver agreement for any grade was seen with grade C of the Della Valle classification system, which showed substantial interobserver reliability (0.60<=kappa<0.80). The Della Valle classification system may be slightly better in patients with large amounts of heterotopic ossification, but both classification systems lack sufficient clarity and are open to significant subjective interpretation. [Orthopedics. 2017; 40(1):e54-e58.]. PMID- 27684083 TI - Visibility of Tinted Chlorhexidine Gluconate Skin Preparation on Varied Skin Pigmentations. AB - Preoperative skin preparation with antimicrobial agents decreases the risk of surgical site infection, but concerns have been raised about the visibility of a common surgical preparatory agent (ChloraPrep; Becton, Dickinson & Co, Franklin Lakes, New Jersey), depending on skin pigmentation. Poor visibility may lead to failure to identify inadequately prepared skin, increasing the risk of surgical site infection. This study was conducted to determine whether different tints of ChloraPrep and different skin pigmentations affect the ability of orthopedic surgeons to identify the adequacy of skin preparation. The forearms of volunteers in 4 skin pigmentation categories (fair, medium-fair, medium-dark, and dark) were prepared with Hi-Lite Orange and Scrub Teal ChloraPrep, with 1 forearm prepared adequately and 1 prepared inadequately. Videos showing the forearms were obtained and compiled into a survey that was sent to orthopedic surgeons, who were asked to assess the adequacy of skin preparation. When the 4 pigmentation categories were aggregated, no difference was noted between Hi-Lite Orange and Scrub Teal tints in rates of correct identification of adequate skin preparation by respondents. When the preparation tint was not controlled for, respondents correctly identified the adequacy of skin preparation for fair and medium-fair pigmentations, but not for medium-dark and dark skin pigmentations. The Hi-Lite Orange tint was significantly easier to identify on fair and medium-fair skin pigmentations, and the Scrub Teal tint was easier to identify on medium-dark and dark skin pigmentations. To reduce the risk of surgical site infection, surgeons should use Hi-Lite Orange on patients whose skin is fair or medium-fair and Scrub Teal on patients whose skin is medium-dark or dark. [Orthopedics. 2017; 40(1):e44 e48.]. PMID- 27684084 TI - Spondylolysis and End Plate Arthrosis at L5-S1: A Cadaveric Study. AB - This study examined the effect of bilateral and unilateral L5 pars defects on the degree of disk degeneration at the L5-S1 level in cadaveric specimens. An observational study was performed of 690 cadaveric specimens selected at random. These specimens represent individuals who died between 1893 and 1938. The study included 558 male and 132 female cadavers. Of the 120 specimens with L5 spondylolysis, 95 cases were bilateral and 25 were unilateral. The remaining 544 specimens were used as the control cohort. Degenerative disk disease was measured by the classification of Eubanks et al. According to this classification, degenerative disk disease was graded from no arthrosis (grade 0) to complete ankylosis (grade IV). Linear regression analysis corrected for age, sex, and race showed that subjects with bilateral spondylolysis at L5 had a statistically significant increase in the amount of disk degeneration (P=.02) compared with those with unilateral lesions. Student's t tests showed significant differences (P<.001 and P=.002, respectively) in the amount of degeneration seen with both bilateral and unilateral spondylolysis above what would be predicted in the normal control population. A positive correlation was found between the number of pars defects at L5 and the degree of disk degeneration at L5-S1. These results support the idea that individuals with spondylolysis at these levels may be at increased risk for development of low back pain and reduced quality of life. [Orthopedics. 2017; 40(1):e59-e64.]. PMID- 27684085 TI - Preliminary Trial of Intra-articular LMWF-5A for Osteoarthritis of the Knee. AB - This study was conducted to investigate the safety and efficacy of 3 intraarticular injections of the low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) administered every 2 weeks for knee pain as a result of osteoarthritis. This single-center, randomized, vehicle-controlled, double-blind, phase II study was designed to ensure the safety of multiple intra-articular injections of LMWF-5A and to explore its efficacy in reducing pain as a result of knee osteoarthritis. Patients were randomized 1:1 to receive 3 biweekly intra articular knee injections of either 4 mL LMWF-5A or vehicle control (saline), administered at weeks 0 (baseline), 2, and 4. Safety was examined as the incidence and severity of adverse events. Efficacy was assessed by the mean (SD) change between treatment groups in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 20. A total of 40 patients were randomized and received treatment. No drug-related serious adverse events and no deaths were reported. Adverse events were similar in patients who received saline (18, 90%) and LMWF-5A (19, 95%). Those treated with LMWF-5A had a significant decrease in pain at 20 weeks compared with the saline group (-1.41 [SD, 0.81] vs -0.85 [SD, 0.64], P=.02), corresponding to improvement in pain at week 20 of 64% with LMWF-5A compared with 40% with saline. This preliminary clinical trial showed that repeated intra-articular injections of LMWF-5A are safe when administered at 2-week intervals and are effective in providing relief of the pain of osteoarthritis of the knee at 20 weeks. [Orthopedics. 2017; 40(1):e49-e53.]. PMID- 27684086 TI - Serum Cartilage Biomarkers and Shoulder Instability. AB - Differences in cartilage biomarkers have been noted in patients with anterior cruciate ligament tears, but little is known about any similar relationship with shoulder instability. This study evaluated the relationship between serum cartilage biomarkers and shoulder instability. The authors present a prospective cohort study of young athletes followed from 2006 to 2010. A nested case-control analysis was conducted within this cohort to evaluate the association between preinjury collagen type II cleavage (a marker for type II collagen cleavage) and procollagen II carboxy propeptide (a marker of cartilage synthesis) and the subsequent likelihood of shoulder instability during the 4-year follow-up period. Preinjury collagen type II cleavage and procollagen II carboxy propeptide levels in 51 subjects who had shoulder instability were compared with levels in 210 subjects without documented anterior cruciate ligament or shoulder instability (control group) with commercially available enzyme-linked immunosorbent assay kits. Mean preinjury collagen type II cleavage levels in patients who subsequently had shoulder instability were significantly lower than those in the control group (73.91 vs 79.24 pg/mL, P=.03). No significant difference was found in preinjury procollagen II carboxy propeptide levels compared with the control group (359.94 vs 396.37, P=.24). This study is the first to examine the relationship between baseline collagen biomarkers and subsequent shoulder instability. The finding of lower baseline collagen type II cleavage levels in patients with subsequent shoulder instability may represent a genetic predisposition or a compensatory mechanism by which cartilage degradation is decreased in those who are more likely to have instability. [Orthopedics. 2017; 40(1):34-36.]. PMID- 27684087 TI - Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1. AB - Macrophages are phagocytic cells that play a major role at the crossroads between innate and specific immunity. They can be infected by the human immunodeficiency virus (HIV)-1 and because of their resistance to its cytopathic effects they can be considered to be persistent viral reservoirs. In addition, HIV-infected macrophages exhibit defective functions that contribute to the development of opportunistic diseases. The exact mechanism by which HIV-1 impairs the phagocytic response of macrophages was unknown. We had previously shown that the uptake of various particulate material by macrophages was inhibited when they were infected with HIV-1. This inhibition was only partial and phagosomes did form within HIV infected macrophages. Therefore, we focused on analyzing the fate of these phagosomes. Phagosome maturation is accompanied by migration of these compartments towards the cell center, where they fuse with lysosomes, generating phagolysosomes, responsible for degradation of the ingested material. We used IgG opsonized Sheep Red Blood Cells as a target for phagocytosis. To measure the speed of centripetal movement of phagosomes in individual HIV-infected macrophages, we used a combination of bright field and fluorescence confocal microscopy. We established a method to calculate the distance of phagosomes towards the nucleus, and then to calculate the velocity of the phagosomes. HIV infected cells were identified thanks to a GFP-expressing virus, but the method is applicable to non-infected cells or any type of infection or treatment. PMID- 27684088 TI - Ordering Single Cells and Single Embryos in 3D Confinement: A New Device for High Content Screening. AB - Biological cells are usually observed on flat (2D) surfaces. This condition is not physiological, and phenotypes and shapes are highly variable. Screening based on cells in such environments have therefore serious limitations: cell organelles show extreme phenotypes, cell morphologies and sizes are heterogeneous and/or specific cell organelles cannot be properly visualized. In addition, cells in vivo are located in a 3D environment; in this situation, cells show different phenotypes mainly because of their interaction with the surrounding extracellular matrix of the tissue. In order to standardize and generate order of single cells in a physiologically-relevant 3D environment for cell-based assays, we report here the microfabrication and applications of a device for in vitro 3D cell culture. This device consists of a 2D array of microcavities (typically 10(5) cavities/cm(2)), each filled with single cells or embryos. Cell position, shape, polarity and internal cell organization become then normalized showing a 3D architecture. We used replica molding to pattern an array of microcavities, 'eggcups', onto a thin polydimethylsiloxane (PDMS) layer adhered on a coverslip. Cavities were covered with fibronectin to facilitate adhesion. Cells were inserted by centrifugation. Filling percentage was optimized for each system allowing up to 80%. Cells and embryos viability was confirmed. We applied this methodology for the visualization of cellular organelles, such as nucleus and Golgi apparatus, and to study active processes, such as the closure of the cytokinetic ring during cell mitosis. This device allowed the identification of new features, such as periodic accumulations and inhomogeneities of myosin and actin during the cytokinetic ring closure and compacted phenotypes for Golgi and nucleus alignment. We characterized the method for mammalian cells, fission yeast, budding yeast, C. elegans with specific adaptation in each case. Finally, the characteristics of this device make it particularly interesting for drug screening assays and personalized medicine. PMID- 27684090 TI - Rotational Spectrum, Structure, and Interaction Energy of the Trifluoroethylene...Carbon Dioxide Complex. AB - Rotational spectra for four isotopologues of the 1:1 weakly bound complex between trifluoroethylene (HFC?CF2) and carbon dioxide (CO2) were recorded using 480 MHz bandwidth chirped-pulse and resonant cavity Fourier transform microwave spectroscopy between 5.0 and 18.5 GHz. Two planar forms are possible: experimental rotational constants, planar moments, and dipole moment components are consistent with the form in which CO2 is positioned at the CHF end of the TFE subunit and is approximately perpendicular to the C?C bond; the other form, with CO2 aligned roughly parallel to the C?C bond, is not observed, consistent with ab initio relative energy predictions. Symmetry-adapted perturbation theory (SAPT) calculations provided interaction energies for possible structural forms of this complex, and comparisons are made with this and other members of the series of carbon dioxide complexes with fluorinated ethylenes (vinyl fluoride, 1,1 difluoroethylene, cis- and trans-1,2-difluoroethylene, and trifluoroethylene). PMID- 27684089 TI - High-Throughput, Multi-Image Cryohistology of Mineralized Tissues. AB - There is an increasing need for efficient phenotyping and histopathology of a variety of tissues. This phenotyping need is evident with the ambitious projects to disrupt every gene in the mouse genome. The research community needs rapid and inexpensive means to phenotype tissues via histology. Histological analyses of skeletal tissues are often time consuming and semi-quantitative at best, regularly requiring subjective interpretation of slides from trained individuals. Here, we present a cryohistological paradigm for efficient and inexpensive phenotyping of mineralized tissues. First, we present a novel method of tape stabilized cryosectioning that preserves the morphology of mineralized tissues. These sections are then adhered rigidly to glass slides and imaged repeatedly over several rounds of staining. The resultant images are then aligned either manually or via computer software to yield composite stacks of several layered images. The protocol allows for co-localization of numerous molecular signals to specific cells within a given section. In addition, these fluorescent signals can be quantified objectively via computer software. This protocol overcomes many of the shortcomings associated with histology of mineralized tissues and can serve as a platform for high-throughput, high-content phenotyping of musculoskeletal tissues moving forward. PMID- 27684091 TI - Sequential Deprotonation-Alkylation of Binaphthyloxy-Substituted Phosphonochalcogenoates: Chiral Tri- and Tetrasubstituted Carbon Centers Adjacent to a Phosphorus Atom. AB - Sequential deprotonation and alkylation of 1,1'-binaphthyloxy-substituted phosphonoselenoates and phosphonates resulted in the diastereoselective formation of chiral tri- and tetrasubstituted carbon centers adjacent to a phosphorus atom. PMID- 27684092 TI - An Innovative Running Wheel-based Mechanism for Improved Rat Training Performance. AB - This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity for reducing the severity of the effects of the stroke in rats. This system provides more effective animal exercise training than commercially available systems such as treadmills and motorized running wheels (MRWs). In contrast to an MRW that can only achieve speeds below 20 m/min, rats are permitted to run at a stable speed of 30 m/min on a more spacious and high-density rubber running track supported by a 15 cm wide acrylic wheel with a diameter of 55 cm in this work. Using a predefined adaptive acceleration curve, the system not only reduces the operator error but also trains the rats to run persistently until a specified intensity is reached. As a way to evaluate the exercise effectiveness, real-time position of a rat is detected by four pairs of infrared sensors deployed on the running wheel. Once an adaptive acceleration curve is initiated using a microcontroller, the data obtained by the infrared sensors are automatically recorded and analyzed in a computer. For comparison purposes, 3 week training is conducted on rats using a treadmill, an MRW and a PRW. After surgically inducing middle cerebral artery occlusion (MCAo), modified neurological severity scores (mNSS) and an inclined plane test were conducted to assess the neurological damages to the rats. PRW is experimentally validated as the most effective among such animal mobility systems. Furthermore, an exercise effectiveness measure, based on rat position analysis, showed that there is a high negative correlation between the effective exercise and the infarct volume, and can be employed to quantify a rat training in any type of brain damage reduction experiments. PMID- 27684093 TI - Unimolecular Micelles of Amphiphilic Cyclodextrin-Core Star-Like Copolymers with Covalent pH-Responsive Linkage of Anticancer Prodrugs. AB - Multifunctional stable and stimuli-responsive drug delivery systems are important for efficient cancer treatment due to their advantages such as enhanced cancer targeting efficiency, improved pharmacokinetics, minimized drug leaching, and reduced undesirable side effects. Here we report a robust and pH-responsive anticancer drug delivery system based on unimolecular micelles of star-like amphiphilic copolymers. The polymers (denoted as CPOFs) were facilely synthesized via one-step atom transfer radical polymerization of functionalizable benzoaldehyde and hydrophilic poly[(oligo ethylene glycol) methyl ether methacrylate] as comonomers from the core of heptakis [2,3,6-tri-o-(2-bromo-2 methyl propionyl]-beta-cyclodextrin as the initiator. Doxorubicin (DOX) as an anticancer drug was covalently linked to the benzoaldehyde groups of CPOFs through pH-sensitive Schiff-base bonds. The DOX-conjugated polymers, denoted as CPOF-DOX, formed robust unimolecular micelles with an average diameter of 18 nm in aqueous media. More importantly, these unimolecular micelles showed higher drug loading capacity and more controllable drug release characteristics, compared to our previous unimolecular micelles of beta-cyclodextrin-poly(lactic acid)-b-poly[(oligo ethylene glycol) methyl ether methacrylates] that physically encapsulated DOX via hydrophobic interaction. Moreover, the CPOF-DOX unimolecular micelles could be internalized by human cervical cancer HeLa cells in a stepwise way and showed less cytotoxicity compared to carrier-free DOX. We foresee that CPOF-DOX would provide a promising robust and controllable anticancer drug delivery system for future animal study and clinical trials for cancer treatment. PMID- 27684095 TI - Charge Transfer to Solvent Dynamics at the Ambient Water/Air Interface. AB - Electron-transfer reactions at ambient aqueous interfaces represent one of the most fundamental and ubiquitous chemical reactions. Here the dynamics of the charge transfer to solvent (CTTS) reaction from iodide was probed at the ambient water/air interface by phase-sensitive transient second-harmonic generation. Using the three allowed polarization combinations, distinctive dynamics assigned to the CTTS state evolution and to the subsequent solvating electron-iodine contact pair have been resolved. The CTTS state is asymmetrically solvated in the plane of the surface, while the subsequent electron solvation dynamics are very similar to those observed in the bulk, although slightly faster. Between 3 and 30 ps, a small phase shift distinguishes an electron bound in a contact pair with iodine and a free hydrated electron at the water/air interface. Our results suggest that the hydrated electron is fully solvated in a region of reduced water density at the interface. PMID- 27684094 TI - Working with Auditory HEI-OC1 Cells. AB - HEI-OC1 is one of the few mouse auditory cell lines available for research purposes. Originally proposed as an in vitro system for screening of ototoxic drugs, these cells have been used to investigate drug-activated apoptotic pathways, autophagy, senescence, mechanism of cell protection, inflammatory responses, cell differentiation, genetic and epigenetic effects of pharmacological drugs, effects of hypoxia, oxidative and endoplasmic reticulum stress, and expression of molecular channels and receptors. Among other several important markers of cochlear hair cells, HEI-OC1 cells endogenously express prestin, the paradigmatic motor protein of outer hair cells. Thus, they can be very useful to elucidate novel functional aspects of this important auditory protein. HEI-OC1 cells are very robust, and their culture usually does not present big complications. However, they require some special conditions such as avoiding the use of common anti-bacterial cocktails containing streptomycin or other antibiotics as well as incubation at 33 degrees C to stimulate cell proliferation and incubation at 39 degrees C to trigger cell differentiation. Here, we describe how to culture HEI-OC1 cells and how to use them in some typical assays, such as cell proliferation, viability, death, autophagy and senescence, as well as how to perform patch-clamp and non-linear capacitance measurements. PMID- 27684096 TI - Taste-Guided Isolation of Bitter Lignans from Quercus petraea and Their Identification in Wine. AB - Quercoresinosides A and B (1 and 2), two new lignans, were isolated from a toasted Quercus petraea heartwood extract along with a known compound, 3-methoxy 4-hydroxyphenol 1-O-beta-d-(6'-O-galloyl)glucopyranoside (3). The purification protocol was based on a taste-guided approach that sought to reveal new bitter compounds released from oak wood into wines and spirits. HRMS and NMR data were used to establish that compounds 1 and 2 are lignan derivatives bearing a glucosyl unit and a galloyl unit at the same positions. Hydrolysis of these compounds showed that they could be distinguished by the absolute configuration of their respective lyoniresinol genin as determined by chiral LC-HRMS in comparison with (+)- and (-)-lyoniresinol standards. Sensory analyses were performed in a non-oaked wine on the pure compounds 1-3. The three molecules exhibited a bitter taste at 2 mg/L that was particularly intense for compounds 2 and 3. Finally, LC-HRMS demonstrated the occurrence of compounds 1-3 in oaked wine and brandy, which supports the hypothesis of their contributions to the increase in bitterness during oak aging. PMID- 27684097 TI - Characterizing Multiscale Mechanical Properties of Brain Tissue Using Atomic Force Microscopy, Impact Indentation, and Rheometry. AB - To design and engineer materials inspired by the properties of the brain, whether for mechanical simulants or for tissue regeneration studies, the brain tissue itself must be well characterized at various length and time scales. Like many biological tissues, brain tissue exhibits a complex, hierarchical structure. However, in contrast to most other tissues, brain is of very low mechanical stiffness, with Young's elastic moduli E on the order of 100s of Pa. This low stiffness can present challenges to experimental characterization of key mechanical properties. Here, we demonstrate several mechanical characterization techniques that have been adapted to measure the elastic and viscoelastic properties of hydrated, compliant biological materials such as brain tissue, at different length scales and loading rates. At the microscale, we conduct creep compliance and force relaxation experiments using atomic force microscope-enabled indentation. At the mesoscale, we perform impact indentation experiments using a pendulum-based instrumented indenter. At the macroscale, we conduct parallel plate rheometry to quantify the frequency dependent shear elastic moduli. We also discuss the challenges and limitations associated with each method. Together these techniques enable an in-depth mechanical characterization of brain tissue that can be used to better understand the structure of brain and to engineer bio inspired materials. PMID- 27684098 TI - Outbreak of trichinellosis related to eating imported wild boar meat, Belgium, 2014. AB - Trichinellosis is a rare parasitic zoonosis caused by Trichinella following ingestion of raw or undercooked meat containing Trichinella larvae. In the past five years, there has been a sharp decrease in human trichinellosis incidence rates in the European Union due to better practices in rearing domestic animals and control measures in slaughterhouses. In November 2014, a large outbreak of trichinellosis occurred in Belgium, related to the consumption of imported wild boar meat. After a swift local public health response, 16 cases were identified and diagnosed with trichinellosis. Of the 16 cases, six were female. The diagnosis was confirmed by serology or the presence of larvae in the patients' muscle biopsies by histology and/or PCR. The ensuing investigation traced the wild boar meat back to Spain. Several batches of imported wild boar meat were recalled but tested negative. The public health investigation allowed us to identify clustered undiagnosed cases. Early warning alerts and a coordinated response remain indispensable at a European level. PMID- 27684100 TI - Pre-clinical Orthotopic Murine Model of Human Prostate Cancer. AB - To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model. PMID- 27684099 TI - Different modalities of entry in a large urban clinic in Uganda and impact on outcomes of patients assessing HIV care and treatment. AB - In resource-limited settings, a number of patients do not receive continuous HIV care. In this analysis, we compared outcomes in patients who entered care by different modality of entry. This was a retrospective analysis of all patients started on antiretroviral treatment (ART) at a large urban center in Uganda from 2005 to 2012. Patients were categorized into three groups (1) Front door: started on ART without interruption during follow-up; (2) drop-out side door: restarted on ART after having an interruption >6 months and (3) transfer-in side door: transferred-in after being started on ART somewhere else. We compared characteristics at enrollment in the three groups and investigated the following outcomes: (1) retention in care (2) switch to second line. In the study period 11,528 (87.2%) were enrolled through the front door, 1159 (8.7%) resumed ART after dropping out, while 527 (4%) patients were transferred in on ART. The three groups were generally comparable, although patients transferred in were sicker. A larger proportion of patients entered through the drop-out side door died or was lost to follow-up (37.3%), as compared to patients in the front door group (24.9%) and transferred-in side door group (17.7%). More patients in the front door group (32.1%) were transferred out during the follow-up. The highest probability of switching to second line was found in the transferred-in group. Patients who re-enter our program after dropping out are at higher risk of dropping out of care and often need to be switched to second-line ART. The high demand for second-line therapy among patients in transfer-in side door reflects failure in management of complicated patients who are usually require "up transfer" to better treatment centers. In future understanding, the different modes of entry into HIV care will be key in reshaping the general cascade of HIV care. PMID- 27684101 TI - Polychelated cryogels: hemoglobin adsorption from human blood. AB - The separation and purification methods are extremely important for the hemoglobin (Hb) which is a crucial biomolecule. The adsorption technique is popular among these methods and the cryogels have been used quite much due to their macropores and interconnected flow channels. In this study, the Hb adsorption onto the Cu(II) immobilized poly(2-hydroxyethyl methacrylate-glycidyl methacrylate), poly(HEMA-GMA)-Cu(II), cryogels was investigated under different conditions (pH, interaction time, initial Hb concentration, temperature and ionic strength) to optimize adsorption conditions. The swelling test, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), surface area (BET), elemental and ICP-OES analysis were performed for the characterization of cryogels. Polyethyleneimine (PEI) molecule was used as a Cu(II)-chelating ligand. The Hb adsorption capacity of cryogels was determined as 193.8 mg Hb/g cryogel. The isolation of Hb from human blood was also studied under optimum adsorption conditions determined and the Hb (124.5 mg/g cryogel) was isolated. The adsorption model was investigated in the light of Langmuir and Freundlich adsorption isotherm models and it was determined to be more appropriate to the Langmuir adsorption isotherm model. PMID- 27684102 TI - Psilocybin for treating substance use disorders? AB - INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions. Areas covered: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size. PMID- 27684104 TI - Feeling blue at the end of life: Trajectories of depressive symptoms from a distance-to-death perspective. AB - This article examines the end-of-life development of depressive symptoms and characterizes prototypical groups following the same depressive symptoms development. We modeled time-to-death-related trajectories of depressive symptoms (Center for Epidemiologic Studies Depression Scale), applying a latent class growth analysis to deceased older adults from the English Longitudinal Study of Aging (Waves 1 to 5; NTime 1 (T1) = 2,219; MAge(T1) = 73.9 years, SDAge(T1) = 9.4 years; 51% male, 1% non-White). Four prototypical trajectories of depressive symptoms were identified at the end of life: a stably nondepressed group (31.2%); 2 groups with an exponential terminal symptom increase, of which 1 was nondepressed and 1 low depressed (8.3% and 38.4%, respectively); and a stably depressed group (22.2%). Using a combination of growth curve models and individual level and slope values as predictor variables showed that individuals suffering from increasing sensory, mobility, or overall health problems or decreasing quality of life were more likely to have an increase in symptoms of depression in their last years of life. Men were more likely to be stably nondepressed and women more likely to be chronically depressed. We conclude that a group-based analysis of end-of-life depressive symptoms is useful in adding to the understanding of distance-to-death psychology at large as well as pointing to preventive and intervention strategies when it comes to late-life depressive mood. (PsycINFO Database Record PMID- 27684105 TI - Risk taking across the life span: A comparison of self-report and behavioral measures of risk taking. AB - Aging has long been thought to be associated with changes in risk-taking propensity. But do different measures converge in showing similar age-related patterns? We conducted a study to investigate the convergent validity of different self-report and behavioral assessments of risk taking across adulthood (N = 902). Individuals between 18 and 90 years of age answered a self-report item and completed 2 incentivized behavioral tasks: a gambles task and the Balloon Analogue Risk Task. Our results indicate that although all measures show some patterns indicative of an age reduction in risk taking, the correlations between measures are small. Moreover, age differences in behavioral paradigms seem to emerge as a function of specific task characteristics, such as learning and computational demands. We discuss the importance of understanding how specific task characteristics engender age differences in risk taking and the need for future work that disentangles task demands from true age-related changes in risk taking propensity. (PsycINFO Database Record PMID- 27684106 TI - Longitudinal purpose in life trajectories: Examining predictors in late midlife. AB - Research shows midlife adults consistently report higher purpose in life (PIL) than older adults. However, less is known about the changes in PIL during the transition from midlife to older adulthood. This study examined 5-year changes of PIL among late-midlife adults in the Foley Longitudinal Study of Adulthood (n = 163, MAge = 56.37). Results showed that most midlife adults reported higher stable PIL whereas some of them showed lower-stable PIL, with trait conscientiousness and race being significant predictors of PIL. Future studies should investigate when PIL tends to stabilize and how personality and racial experiences influence the development of PIL. (PsycINFO Database Record PMID- 27684103 TI - Daily events are important for age differences in mean and duration for negative affect but not positive affect. AB - Across midlife and into old age, older adults often report lower levels of negative affect and similar if not higher levels of positive affect than relatively younger adults. Researchers have offered a simple explanation for this result: Age is related to reductions in stressors and increases in pleasurable activities that result in higher levels of well-being. The current study examines subjective reports of emotional experience assessed across 8 days in a large sample of adults (N = 2,022) ranging from 35 to 84 years old. By modeling age differences before and after adjusting for daily positive uplifts and negative stressors, this article assesses the extent to which daily events account for age differences in positive and negative affect reports. Consistent with previous research, the authors found that older age is related to lower mean levels and shorter duration of a negative emotional experience in a model only adjusting for gender, education, and ethnicity. After adjusting for daily events, however, the linear age-related effects were no longer significant. For positive affect, adjusting for daily events did not alter age-related patterns of experiencing higher mean levels and longer positive experience duration, suggesting that other factors underlie age-related increases in positive affect. (PsycINFO Database Record PMID- 27684108 TI - Living with transversal upper limb reduction deficiency: limitations experienced by young adults during their transition to adulthood. AB - INTRODUCTION: During transition to adulthood young adults with disabilities are at risk of experiencing limitations due to changing physical and social requirements. PURPOSE: To determine whether young adults with transversal upper limb reduction deficiency (tULRD) have experienced limitations in various domains of participation during transition to adulthood and how they dealt with these limitations. PARTICIPANTS: Fifteen participants (mean age 21.4 years) with tULRD. METHODS: A qualitative study was performed using a semi-structured interview based on the Rotterdam Transition Profile to identify the limitations experienced in participation domains. RESULTS: Almost all the participants reported difficulties in finding a suitable study or job. Most young adults were convinced they were suitable for almost any study or job, but their teachers and potential employers were more reserved. Few difficulties were reported on the domains leisure activities, intimate relationships/sexuality, housing/housekeeping and transportation. Participants preferred to develop their own strategies for dealing with limitations. Various aids, adaptations and prostheses were used to overcome limitations. Rehabilitation teams were infrequently consulted for advice in solving transitional problems. CONCLUSION: Young adults with tULRD experience limitations mainly in choosing and finding a suitable study or job. Rehabilitation teams may play a more extensive role in supporting individuals with transitional problems. Implications for rehabilitation Most young adults with transversal upper limb reduction deficiency (tULRD) experience limitations in study and job selection during transition to adulthood, but they do not consult the rehabilitation team. Assessment of abilities in relation to job interests and practicing job specific bimanual activities may be helpful for young adults with a tULRD. How the rehabilitation teams can meet the needs of young adults with tULRD during transitional phases, when autonomy is of growing importance, should be investigated further. PMID- 27684107 TI - Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis. AB - An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (~60 70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG. PMID- 27684109 TI - Speech rhythm alterations in Spanish-speaking individuals with Alzheimer's disease. AB - Rhythm is the speech property related to the temporal organization of sounds. Considerable evidence is now available for suggesting that dementia of Alzheimer's type is associated with impairments in speech rhythm. The aim of this study is to assess the use of an automatic computerized system for measuring speech rhythm characteristics in an oral reading task performed by 45 patients with Alzheimer's disease (AD) compared with those same characteristics among 82 healthy older adults without a diagnosis of dementia, and matched by age, sex and cultural background. Ranges of rhythmic-metric and clinical measurements were applied. The results show rhythmic differences between the groups, with higher variability of syllabic intervals in AD patients. Signal processing algorithms applied to oral reading recordings prove to be capable of differentiating between AD patients and older adults without dementia with an accuracy of 87% (specificity 81.7%, sensitivity 82.2%), based on the standard deviation of the duration of syllabic intervals. Experimental results show that the syllabic variability measurements extracted from the speech signal can be used to distinguish between older adults without a diagnosis of dementia and those with AD, and may be useful as a tool for the objective study and quantification of speech deficits in AD. PMID- 27684110 TI - Lessons learned in global family medicine education from a Besrour Centre capacity-building workshop. AB - At a global level, institutions and governments with remarkably different cultures and contexts are rapidly developing family medicine centred health and training programmes. Institutions with established family medicine programmes are willing to lend expertise to these global partners but run the risk of imposing a postcolonial, directive approach when providing consultancy and educational assistance. Reflecting upon a series of capacity building workshops in family medicine developed by the Besrour Centre Faculty Development Working Group, this paper outlines approaches to the inevitable challenges that arise between healthcare professionals and educators of differing contexts when attempting to share experience and expertise. Lessons learned from the developers of these workshops are presented in the desire to help others offer truly collaborative, context-centred faculty development activities that help emerging programmes develop their own clinical and educational family medicine frameworks. Established partner relationships, adequate preparation and consultation, and adaptability and sensitivity to partner context appear to be particularly significant determinants for success. PMID- 27684111 TI - Improving Prevention Curricula: Lessons Learned Through Formative Research on the Youth Message Development Curriculum. AB - This article describes formative research (a pilot study, interviews, and focus groups) conducted as part of a feasibility test of 2 versions (Analysis vs. Planning) of a brief media literacy intervention titled Youth Message Development (YMD). The intervention targets high school student alcohol use with activities to understand persuasion strategies, increase counter-arguing, and then apply these new skills to ad analysis or a more engaging ad poster planning activity. Based on the theory of active involvement (Greene, 2013), the Planning curriculum is proposed to be more effective than the Analysis curriculum. Overall, results of the formative research indicated that students (N = 182) and mentors/teachers (N = 53) perceived the YMD Planning curriculum as more interesting, involving, and novel, and these ratings were associated with increased critical thinking about the impact of advertising, lower alcohol use intentions, and fewer positive expectations about the effects of alcohol use. Qualitative feedback indicated a need to supplement alcohol-focused ad stimuli with ads targeting other advertising images, use incentives and competition-based activities to further enhance student motivation, and provide flexibility to enhance the appropriateness of the curriculum to various settings. These concerns led to the development of a revised curriculum and plans for further study. PMID- 27684112 TI - The Effect of Limited Health Literacy on How Internet Users Learn About Diabetes. AB - The Internet continues to be an important supplemental health information resource for an increasing number of U.S. adults, especially for those with a new or existing chronic condition. Here we examine how people use the Internet to learn about Type 2 diabetes and how health literacy (HL) influences this information-seeking behavior. We analyzed the searches of approximately 2 million people who queried for diabetes-related information on Microsoft's Bing search engine. The HL of searchers was imputed through a community-based HL score. Topics searched were categorized and subsequent websites were assessed for readability. Overall, diabetes information-seeking strategies via the Internet are similar among adults with limited and adequate HL skills. However, people with limited HL take a longer time to read pages that are quickly read by people with adequate HL and vice versa. Information seeking among the former is terminated prematurely, as is evident from a Hidden Markov Model of the search process. Our findings indicate that the reading level required to understand the majority of diabetes-related information is high. Especially on government websites, more than 80% of information requires a reading level corresponding to 7th grade or higher. Our results indicate that individuals with lower HL may disproportionately struggle with Internet searches and fail to get an equivalent benefit from this information resource compared to users with greater HL. Future interventions should target the quality and ease of navigation of health care websites and find ways to leverage other relevant professionals to encourage and promote successful information access on the Web. PMID- 27684114 TI - Editorial. AB - When the chips are down you find out who your friends are. And nurses certainly found foes and unusual allies among the newspaper leader writers and columnists following the RCN's decision to proceed to ballot on removing its rule which prohibits industrial action. Many ethically-challenged journalists dished up a scandalous misrepresentation of the nurses' case, usually under banner headlines about 'fallen angels'. It's a measure of how worried the government is over the pay dispute that the Tory press went all out to dent the public image of nurses. It's a dangerous tack for newspapers, especially when their biased political opinions may not always find favour with readers. Many nurses are among the Daily Mail's readership for instance. After Lynda Lee Potter's outrageous drivel (see letters, page 41 ) one can only wonder how many nurses will continue to buy that newspaper. And there is also a clear gap between the views of informed media commentators and the opinion writers as our round-up of views shows (see features, page 18-21 ). But if nurses have fallen from their angelic status that's no bad thing. It's not an image nurses ever wanted, the irony is that the sections of the press which created and lived off that stereotype are now realising they may have got it wrong. PMID- 27684113 TI - The lives and sexual risk behaviours of rural, closeted men who have sex with men living in Montana. AB - The current study investigated the role of the rural environment in shaping men's decisions to remain closeted about their same-sex sexual activity and the cognitive, affective and behavioural consequences of that decision. In-depth qualitative interviews were conducted with 45 self-identified closeted men who have sex with men living in Montana. Because of the difficulty of finding closeted men, recruitment occurred using the Internet. Interviews were analysed to elicit overall themes influencing men's lives. An Outness Inventory was administered to determine men's perceived level of being 'out' to others. Men reported high levels of stress related to their need to live a double life in an attempt to conform to perceptions of masculinity within the rural cultural environment. Fear of being outed led men to seek out-of-town or out-of-state sexual partners indicating widespread sexual networks and increased risk for HIV infection. While men felt they were able to interact with their communities on a superficial level, many stressed their desire for a deeper sense of connection and social support. The majority of men in this study dreamed of a day when they could express their whole identity without fear. PMID- 27684115 TI - ? AB - There's mortar nursing: student nurses at the Bede, Newcastle and Northumbria College of Health Studies celebrate the college's merger with the University of Northumbria in Newcastle-upon-Tyne. PMID- 27684116 TI - Danish nurses' strike declared illegal. AB - Nurses in Denmark were ordered to end their three-week pay strike last week, after the government passed a law to make the strike illegal. More than 12,000 nurses held the biggest strike rally seen in Denmark for 10 years as the legislation was passed. The government will now set up a commission to investigate pay, working conditions and to propose changes. It is due to report back before October this year. PMID- 27684117 TI - UKCC calls on employers to develop a clear policy on sexual harrassment. AB - The UK Central Council has expressed concern over the number of cases of sexual harassment reported to its professional conduct committee. PMID- 27684118 TI - Yorkshire nurse first at the scene of light aircraft crash. AB - Within minutes of a light aircraft crashing in Yorkshire last week a nurse was hunting through the debris in a desperate bid to find survivors. PMID- 27684119 TI - RCN breaks with other unions over pay. AB - Fragile unity between the health unions shattered last week when the RCN broke away from union talks. PMID- 27684120 TI - Morale sinking in London. AB - Morale among nurses in London has sunk to 'rock bottom', claims a report launched last week by the pressure group London Health Emergency. PMID- 27684121 TI - Specialist training needed to deal with incontinence. AB - A major report on the causes and management of incontinence has recommended better training for nurses in both preregistration and post-basic courses. PMID- 27684122 TI - Differing levels of sick leave in NHS. AB - Health service staff take widely differing amounts of sick leave, a survey has shown. PMID- 27684124 TI - Back pain out. AB - A poster campaign aimed at preventing back pain has been launched by the British Safety Council. It urges employers to train employees in lifting techniques. Meanwhile, the National Back Pain Association has published an information booklet on avoiding and coping with back pain. Copies are available by sending a L2 donation to: Information, NBPA, 16 Elm tree Road, Teddington TW11 8ST. PMID- 27684125 TI - RCN concerned about closure plans. AB - Plans to close six colleges of nursing in Northern Ireland and replace them with two educational institutes by the end of June have sparked concerns from the RCN. The Northern Ireland National Board claims the restructuring is due to the decline in student numbers. PMID- 27684126 TI - Trusts facing merger must involve staff. AB - Trusts and health authorities facing merger must involve nurses and other staff in developing the aims of the new organisation, says an Audit Commission report. Dozens of trusts are believed to be considering merger, which, the report claims, causes anxiety among staff who fear for their future. PMID- 27684127 TI - Nurses must fight to get on new boards. AB - Nurses will have to 'fight their corner' in each area of the UK if they want to be represented on the new health authority boards, an NHS management expert has said. PMID- 27684128 TI - Unison condemns sacking. AB - A nurse was sacked to stop him taking forward a grievance against the managers of his unit, Unison has claimed. PMID- 27684129 TI - Bassetlaw nurse remanded in custody. AB - Amanda Jenkinson, the nurse charged with murdering a patient in the intensive care unit of Bassetlaw Hospital, was remanded in custody until June 21 by Worksop magistrates. PMID- 27684130 TI - ? AB - Winners of the Florence Nightingale awards line-up at the recent awards ceremony at the Mansion House in the City of London. Front row, from left: Julia Gilroy, Suzanne Hargreaves, Anthea Major and Shirley Dougherty'; back row; Leslie Chambers, Caroline Birtles, Marion Woan. Donna Morely, Helene Smith, Denise Morris, Margaret Colder and Maggi Jarvis. PMID- 27684131 TI - Fighting childhood asthma. AB - Community nurses, youth dub leaders and major childcare agencies met in London last week to set up an initiative to fight childhood asthma anti improve the well being of children with the condition. PMID- 27684132 TI - Nurse loses court compensation claim. AB - A nurse who claimed she seriously injured her back while giving a lecture called 'Look after yourself has lost her High Court claim for compensation. PMID- 27684133 TI - Survey pinpoints health neurosis. AB - Women, people living alone, those living in urban rented accommodation and the unemployed are the most likely to be neurotic, a major survey of the nation's mental health has found. PMID- 27684134 TI - Collaboration set to tackle wound care problems in nursing homes. AB - A wound care research unit at Guy's Hospital and a private nursing home company have joined forces to tackle the problem area of chronic wound care for older people in long-term nursing homes. PMID- 27684135 TI - ? AB - David Nunn, who with Maura Buchanan, Linda Bailey and Rod Thompson was elected to the Congress agenda committee, which will agree motions for the 1996 Congress in Bournemouth. PMID- 27684136 TI - Means testing of older people firmly rejected. AB - A retired nurse who joined the NITS at its founding told Congress of her sense of betrayal at the means testing of care for elderly people. PMID- 27684137 TI - Nurses used to spy on suspect mothers. AB - Nurses are being used to gather criminal evidence against mothers suspected of abusing their children, a job which should be left to the police, a Congress fringe event heard. PMID- 27684138 TI - Macho culture blamed for poor health statistics of men. AB - The macho male culture prevents many men from owning up to their ill health and seeking treatment, Congress heard. PMID- 27684140 TI - RCN to reconsider policy on cautions after heated debate. AB - RCN Council is to look again at College policy on whether cautions imposed on nurses by the UK Central Council for professional misconduct should be revealed on request to employers. A heated Congress debate agreed to refer the matter to RCN Council due to the complexity of the issues involved. PMID- 27684139 TI - Self-harm treatment often misunderstood by carers. AB - Nurses who care for people who deliberately self-harm are still viewed by many as providing a 'suicide watch', Julie Owens, senior clinical nurse in the Personalities Disorders Department at Ashworth Hospital on Merseyside, told a Congress fringe event. PMID- 27684141 TI - ? AB - Very Important Bear: A non-voting member from the West Midlands Region attempts to raise a point of order and a procedural motion at the same time, no doubt to the displeasure of the Congress chair. PMID- 27684142 TI - Ward managers under pressure. AB - The ward manager's role is pivotal but undervalued, especially in financial terms, a meeting on the RCN Nursing Leadership Project heard. PMID- 27684143 TI - Children's nurses not specialists, seminar told. AB - The health and well-being of children and other client groups would be at risk if nurse education was remodelled as a generic education with specialist add-on qualifications. PMID- 27684145 TI - A hormone predictor of premature labour? AB - Australian researchers believe they have found a hormone which acts as a marker for premature labour. PMID- 27684144 TI - Guidance fills training gaps on ethical issues. AB - Nurses and doctors face the same ethical issues when caring for older people, was the message to a seminar held to mark the launch of The Older Person - Consent and Care, a joint publication from the British Medical Association and the RCN. PMID- 27684146 TI - Increasing compliance with self medication. AB - Self-medication programmes for older people result in significantly higher levels of compliance and understanding after hospital discharge. PMID- 27684147 TI - Viral infections and asthma exacerbations. AB - The majority of exacerbations of asthma in school age children are associated with upper respiratory tract viral infections, new research suggests. PMID- 27684148 TI - Rubber allergy and hepatitis vaccination. AB - Patients should be asked if they have a history of contact allergy to rubber before receiving hepatitis B vaccination. PMID- 27684149 TI - New society promotes Welsh for nurses. AB - Nurses in Wales have formed a new society to promote the Welsh language in their work. The chair of the new society, Eira Rowley, professional adviser to the Welsh National Board for Nursing, said with up to 80 per cent of patients in some areas speaking Welsh as their first language, it is important to speak Welsh wherever possible. Ms Rowley said some patients were penalised because they were not so familiar with English as their mother tongue. PMID- 27684151 TI - ? AB - Public support for the nurses is holding firm, if the reaction of people at Euston station last Tuesday is anything to go by. PMID- 27684150 TI - Attitudes can change. AB - Teamwork and flexibility are vital for nurses aiming to involve patients, a new report says. Five teams at nursing development units have told the authors of a King's Fund publication how they have tried to give patients a greater say in their care. PMID- 27684152 TI - That was the week that was. AB - As the Royal College of Nursing Congress drew to a close in Harrogate members were in no doubt their national pay campaign had gathered momentum. It was no longer just about a 3 per cent pay rise for every nurse in the country, but about the future of the NHS itself. PMID- 27684154 TI - ? AB - If you believe the rhetoric of government ministers and NHS managers, a reason for the introduction of local pay is the opportunity it offers to both sides to negotiate deals which reflect local circumstances. Philip Hunt, director of the National Association of Health Authorities and Trusts, made this point at a press conference at the recent RCN Congress. PMID- 27684153 TI - ...and mixed messages from the media. AB - The decision by RCN Congress to ballot on its no-strike rule prompted a spate of newspaper headlines saying 'angels fall from grace'. PMID- 27684155 TI - In and out of pocket. AB - About half of the UK's 500 trusts had still not made official pay offers to nurses last week. The Royal College of Nursing has called on its members to 'expose employers who persist in dragging their feet on pay offers'. PMID- 27684156 TI - Challenging stress. AB - In November 1994, senior social worker John Walker won a High Court battle for compensation for stress leading to a second mental breakdown. It was the first time anyone had successfully sued an employer in such a case. PMID- 27684157 TI - Rule 12 debate was what it is all about. AB - I have just come out of the rule 12 debate. I am shaking and sweating. The result was historic. It reiterated the purpose of nursing: to care for people enough to safeguard the service in which that care is delivered. I write to say thank you to the Association of Nursing Students for giving me the privilege of attending, and thank you to voting members for giving me a future. PMID- 27684158 TI - We must turn our feelings into votes. AB - Congress has given Council approval for balloting the membership on amending rule 12 of our constitution: an overwhelming 99 per cent in favour! PMID- 27684159 TI - Mail spread was a misrepresentation. AB - I feel I must reply to a double page spread in the Daily Mail (May 20) under the title 'Was this the week our nursing Angels fell from grace?' PMID- 27684160 TI - Family ties between Bugsy and Gerald? AB - I was greatly angered, as indeed was everyone else in the auditorium, when Christine Hancock read out the letter from health minister Gerald Malone. PMID- 27684161 TI - Don't let us fall into strike action trap. AB - The strike weapon is a blunt instrument and there is no strike action that will not in some way affect patients. PMID- 27684162 TI - Are we adventurers or ostriches? AB - One reason why I love the RCN is our amazing capacityto be adventurous one minute, and ostrich-like the next. PMID- 27684163 TI - Are student nurses part of pay picture? AB - Every week in Nursing Standard I read about the fight for the 3 per cent pay rise. As I agree with this wholeheartedly. PMID- 27684164 TI - I wanted to hear members' views. AB - Before Congress, an RCN spokesperson stated in Nursing Standard that Council had decided to hold a questions and discussion panel instead of a ministerial address. This was to stop ministers using Congress for major announcements and to hear more of members' views. I dug in and waited to see before making up my mind about this new system. PMID- 27684165 TI - ? AB - I was at Congress to hear the debate on rule 12, which would allow nurses to take legal industrial action - not strike action. No nurse would take action which would be detrimental to patient care. PMID- 27684166 TI - Spotlight on Irish was very welcome. AB - I was delighted to see the health needs of elderly Irish people highlighted at the breakfast seminar 'Delivering health gain messages to people from black and minority ethnic communities'. PMID- 27684167 TI - Recommending a staff charter. AB - It was suggested by the proposer of a resolution at Congress that with so many other charters around it was time to have a staff charter. PMID- 27684168 TI - Nurses' role in good health services for all. AB - The race and ethnicity subcommittee's breakfast meeting attracted 30 members from a range of backgrounds and clinical specialisms. PMID- 27684169 TI - Time to take stand on non-meat eating. AB - I agree with the points raised by Lynn Sawyer (Letters, May 10) regarding meat eating, BSE and the adoption of a vegan diet. How refreshing to see the issue raised positively. PMID- 27684170 TI - This year was much kinder to the trees. AB - Thank you. Thank you. Last year I wrote a letter about the amount of paper being handed out at Congress. PMID- 27684171 TI - Not everyone had access to congress. AB - May I highlight the fact that some of our members with disabilities were unable to attend Congress events this year because of stairs and other obstacles. Even at the steward's dinner, one member was left in the hallway because there was not enough room for a wheelchair to pass between the tables. PMID- 27684172 TI - Information exchange. AB - I am a staff nurse involved in a quality improvement team looking at integrated casenotes and collaborative care planning. I would welcome any information Amanda Jones, ward 8, Surgical Unit, Yshyty Gian Clwyd Bodeluyddon, Clwyd. PMID- 27684173 TI - Criticism of A&E services was unfair. AB - May I respond to Andrea Martin's 'Your guide to A&E services' (Healthy Debate, May 3). PMID- 27684174 TI - UKCC cannot correct 'abuse' by managers. AB - As an elected member of the UKCC, I applauded the inclusion of the resolution on preceptorship on the agenda as anything which raises the profile of the UKCC and encourages debate is welcome However, after listening to the debate a disquiet began to settle over me. PMID- 27684175 TI - Student view vital in education debate. AB - I want to express my dismay and upset at the events revolving around motion 13 'Standards of nurse education'. How can standards of nurse education be discussed if student nurses and particularly members of the ANS executive sitting on Council, are prevented from voicing the student viewpoint? PMID- 27684176 TI - Readers Panel-How will you vote? AB - Our experts consider a hot topic of the day. PMID- 27684177 TI - Careering ahead through training and development. AB - A new era in neurosurgical care begins in July when the clinical services previously provided by the Brook and Maudsley Hospitals in South London are consolidated with the existing research facilities at King's Healthcare. PMID- 27684178 TI - Listings. AB - August 4-5 Third International Conference on Nurse Practitioner Practice - Cafe Royal, London, UK. Fee: RCN members/NS subscribers L188, non-members L235. Details: Nicola Fulton, Conference and Exhibition Unit, Nursing Standard, Viking House, 17-19 I Peterborough Road, Harrow, Middlesex HA1 2AX. Tel 0181 423 1066. PMID- 27684179 TI - Unusual presentation of trocar site hernia after Roux-en-Y gastric bypass: case report. AB - INTRODUCTION: The exponential increase of bariatric surgery has resulted in a new diagnostic field of postoperative complications. One of the possibly serious complications is trocar site hernia. CASE REPORT: We present a rare case of trocar site hernia, in particular herniation of the blind loop of the jejunojejunostomy in a patient previously operated for laparoscopic gastric bypass. CONCLUSION: In patients with intermittent epigastric pain and regurgitation or nausea after RYGB, the differential diagnosis should include internal herniation and cholecystitis. Besides that, incarcerated trocar site hernia should also be considered. If obstructive symptoms are lacking, this might indicate Richter's hernia or herniation of the blind loop of the jejunojejunostomy. Due to the vague symptoms and the potentially late presentation, diagnosis can be challenging. However, this is a dangerous complication possibly leading to bowel strangulation and perforation, requiring urgent surgical repair. PMID- 27684180 TI - Investigation of resectability degree for adenoidal surgery in OSA children with the method of computational fluid dynamics. AB - CONCLUSION: From aspect of fluid dynamics, expanding patients' nasopharyngeal coronal-sectional area to 48.3-54.7% of normal area will bring the airflow velocity back to normal in adenoidal hypertrophy children. It might provide a suggestion for adenoidectomy range selection and whether total resection is necessary. OBJECTIVES: To evaluate the nasopharyngeal airflow characteristics in pediatric OSA patients with adenoidal hypertrophy, and to explore the proper resection range for adenoidectomy Method: Nine OSA patients and four normal children were recruited. The CT scans of their upper airway were collected and used to construct three dimensional models for fluid dynamics analysis. Using computational fluid dynamics, indices such as velocity, pressure, and coronal sectional area were calculated. RESULTS: Compared with the normal, the OSA children showed three characteristics in nasopharyngeal: the airflow velocity was significantly higher (p < 0.05), the coronal-sectional area was significantly smaller (p < 0.01), while pressure showed no difference (p > 0.05). In a study of the relationship between velocity and coronal-sectional area, this study investigates different coronal-sectional areas from 30-300 mm2. It was found that, when patients' nasopharyngeal coronal-sectional area was expanded over 155 170 mm2, namely 48.3-54.7% of normal area, airflow velocity in nasopharyngeal showed no difference than normal. PMID- 27684182 TI - Welcoming STAR Methods. PMID- 27684181 TI - Influence of hospital characteristics on quality of care in patients with community-acquired pneumonia. AB - PRINCIPLES: In-hospital care of patients with community-acquired pneumonia (CAP) varies across hospitals. Understanding of the underlying factors is the basis for tailored quality improvements. Using data from a randomised controlled Swiss-wide multicentre trial, we compared length of stay (LOS) and other patient outcomes according to (A) the use of a procalcitonin (PCT)-based antibiotic stewardship protocol, (B) institution type (university vs non-university), and (C) historical time period in relation to the introduction of Diagnosis Related Group (DRG) reimbursement (2012). METHODS: We included 784 patients hospitalised with CAP from six institutions into this secondary analysis. We used multivariable regression models adjusted for age, comorbidities and disease severity to determine the influence of institution characteristics on LOS and patient outcomes. FINDINGS: LOS was significantly shorter in the institution using a PCT based antibiotic stewardship protocol (9.2 vs 5.3 days; adjusted mean difference 3.92 days; 95% confidence interval [CI] 5.16-2.68) with shorter antibiotic treatment. There was no difference in LOS in university vs non-university hospitals, but antibiotic courses in university-type hospitals were longer (11.0 vs 8.3 days; adjusted mean difference 2.59 days; 95% CI, 1.69-3.49). No significant difference in LOS was found when comparing the time period before and after the introduction of the DRG system in Switzerland. CONCLUSIONS: We found differences in LOS associated with theuse of a PCT-based antibiotic stewardship protocol, which remained robust after multivariable adjustment. Importantly, the type of institution and model of reimbursement did not influence LOS in our CAP cohort. More health services research studies are needed to establish causal effects. PMID- 27684183 TI - Principles of Systems Biology, No. 9. AB - Deep study of the microbiome, virome, and genetic code headline this month's Cell Systems call (Cell Systems 1, 307). PMID- 27684184 TI - Bringing Functional Genomics into Focus. AB - Styles et al. develop an optimized method that combines high-content microscopy and automated phenotypic analysis with genome-wide yeast genetics to identify genes in DNA damage repair. PMID- 27684185 TI - DNA Structure Helps Predict Protein Binding. AB - Incorporating information about DNA structure can increase the reliability of predictions of transcription factor binding sites. PMID- 27684186 TI - Deconvolution of the Human Endothelial Transcriptome. AB - A systems approach deconvolutes genes specific to and enriched in endothelium from whole-organ transcriptome data, with applications to other cell types and tissues. PMID- 27684188 TI - Measuring Influenza Neuraminidase Inhibition Antibody Titers by Enzyme-linked Lectin Assay. AB - Antibodies to neuraminidase (NA), the second most abundant surface protein on influenza virus, contribute toward protection against influenza. Traditional methods to measure NA inhibiting (NI) antibody titers are not practical for routine serology. This protocol describes the enzyme-linked lectin assay (ELLA), a practical alternative method to measure NI titers that is performed in 96 well plates coated with a large glycoprotein substrate, fetuin. NA cleaves terminal sialic acids from fetuin, exposing the penultimate sugar, galactose. Peanut agglutinin (PNA) is a lectin with specificity for galactose and therefore the extent of desialylation can be quantified using a PNA-horseradish peroxidase conjugate, followed by addition of a chromogenic peroxidase substrate. The optical density that is measured is proportional to NA activity. To measure NI antibody titers, serial dilutions of sera are incubated at 37 degrees C O/N on fetuin-coated plates with a fixed amount of NA. The reciprocal of the highest serum dilution that results in >=50% inhibition of NA activity is designated as the NI antibody titer. The ELLA provides a practical format for routine evaluation of human antibody responses following influenza infection or vaccination. PMID- 27684189 TI - Comparison of the effects of mini-implant and traditional anchorage on patients with maxillary dentoalveolar protrusion. AB - OBJECTIVE: To compare the treatment effects of mini-implants as anchor units with conventional methods of anchorage reinforcement in maxillary dentoalveolar protrusion patients in terms of skeletal, dental, and soft tissue changes. MATERIALS AND METHODS: We searched the databases of the Cochrane Library, PubMed, OVIDSP, CBM, VIP, WanFang Data, and CNKI covering December 1966 to March 2016 for randomized controlled trials (RCTs) and clinical controlled trials that compared the treatment effects of mini-implants with conventional anchorage reinforcement in maxillary dentoalveolar protrusion patients. Literature filtering, data extraction, and methodological quality evaluation were finished independently by two researchers and disagreements were solved by discussion. Meta-analysis was performed when possible; otherwise descriptive assessment was done. RESULTS: Through a predefined search strategy, we finally included 14 eligible studies. Eight outcomes were evaluated in this study: maxillary incisor retraction, maxillary molar movement, U1-SN, SNA, SN-MP, UL-E Plane, NLA and G-Sn-Pg. CONCLUSIONS: Mini-implant anchorage was more effective in retracting the anterior teeth, produced less anchorage loss, and had a greater effect on SN-MP for the high-angle patients than did traditional anchorage. Both mini-implants and traditional anchorage underwent decreases in on U1-SN and SNA. More qualified RCTs are required to make reliable recommendations about the anchorage capacity of mini-implant and traditional anchorage in patients with maxillary dentoalveolar protrusion, especially on the UL-E plane, NLA, and G-Sn-Pg. PMID- 27684187 TI - Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in beta-Catenin-Active Cancers. AB - Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches. We interrogated 177 genes that we classified as essential for the proliferation of cancer cells exhibiting constitutive beta-catenin activity and integrated data for each of the candidates, derived from orthogonal short hairpin RNA (shRNA) knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated gene editing knockout screens, to yield 69 validated genes. We then characterized the relationships between sets of these genes using complementary assays: medium throughput stable isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry, yielding 3,639 protein-protein interactions, and a CRISPR mediated pairwise double knockout screen, yielding 375 combinations exhibiting greater- or lesser-than-additive phenotypic effects indicating genetic interactions. These studies identify previously unreported regulators of beta catenin, define functional networks required for the survival of beta-catenin active cancers, and provide an experimental strategy that may be applied to define other signaling networks. PMID- 27684190 TI - Eruption rates of lower second premolars at different development stages evaluated with cone-beam computed tomography. AB - OBJECTIVE: To evaluate and compare the eruption rates of lower second premolars (LPm2) at different developmental stages using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Retrospectively, 31 individuals (9.77 +/- 1.25 years) had their LPm2 scored according to the Demirjian method, and afterwards they were split into three groups according to developmental stage, as follows: D = complete-formed crowns; E = root length less than crown height; and F = root length greater than or equal to crown height. Linear distances from the LPm2 crown tip to the anatomical reference line (ARL) and to the occlusal plane line (OPL) were measured in paired CBCT scans (T1, T2), taken with an average interval of 8.6 months between them. Eruption rates (mm/y) were calculated and then compared between groups. RESULTS: Eruption rates were greater for LPm2 at stage F than at stages D or E (P < .01) regardless of whether they were measured from the ARL (D = 2.84 mm/y; E = 2.55 mm/y; F = 5.38 mm/y) or from the OPL (D = 1.82 mm/y; E = 2.02 mm/y; F = 5.26 mm/y). Eruption rates evaluated from the ARL and the OPL had no statistically significant differences (P = .052), and a positive correlation (r = .79, P < .001) between them was observed. CONCLUSIONS: LPm2 at Demirjian stage F showed greater eruption rates than at stages D or E, regardless of whether rates were measured from the ARL or the OPL. Faster eruption is expected for LPm2 at stage F. Evaluation of the LPm2's developmental stage using CBCT can aid in clinical decision making regarding the correct timing for intervention. PMID- 27684191 TI - Anti-Inflammatory Potential of Hecogenin in Experimental Animals: Possible Involvement of Inflammatory Cytokines and Myeloperoxidase. AB - Hecogenin is a steroidal sapogenin plays important role in treatment of variety of inflammatory diseases. We have investigated the anti-inflammatory effects of Hecogenin (50 ug/animal) (HG), Fluticasone (50 ug/animal) (FC) and Hecogenin+Fluticasone (HG+FC) combination (25 ug/animal, each) on various inflammatory models. The anti-inflammatory effect of HG, FC and HG+FC combination was studied on % inhibition of dry weight of granuloma tissue, Delta ear weight, myeloperoxidase assay, serum pro-inflammatory cytokines, colon weight to length ratio, macroscopic lesions, adhesion score, diarrhoea score and histopathological analysis of ear and colon tissue on Cotton pellets induced granuloma in rats, Croton oil induced ear edema in mice and TNBS induced granuloma in rats. Topical administration of HG and its combination with FC showed significant decrease (p<0.001) in the % inhibition of dry weight of granuloma tissue, Delta ear weight, myeloperoxidase level, serum pro-inflammatory cytokines levels, colon weigh to length ratio as compared with Cotton pellets treated with acetone groups and Croton oil treated animals. Further histopathological analysis of ear tissue showed significant decrease in dermal thickness and epidermal hyperplasia and colon tissue showed reduction of edema, infiltration of inflammatory cells and normalization of crypt structure compared to DC animals. Thus, the findings of present study suggest the possible role of HG in the treatment of inflammation by reducing the dose of FC in combination with HG. PMID- 27684192 TI - Co-inhibition of Notch and NF-kappaB Signaling Pathway Decreases Proliferation through Downregulating IkappaB-alpha and Hes-1 Expression in Human Ovarian Cancer OVCAR-3 Cells. AB - Background: Ovarian cancer is one of the most lethal gynecological malignancies and numerous changes in signaling cascades are involved in the initiation and progression of ovarian cancerous cells. Here, we investigated the role of NF kappaB and Notch pathways inhibition on human ovarian cancer OVCAR-3 cells proliferation and IkappaB-alpha and Hes-1 expression as 2 key genes in these pathways regulation. Methods: The effects of Bay 11-7085 and DAPT, NF-kappaB and Notch pathways specific inhibitors, on cell proliferation were evaluated using MTT assay. In addition, the cells were transfected by Notch and IKK-beta siRNAs. mRNA and protein levels of target genes were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot after 48 h incubation with inhibitors and siRNAs. Results: Bay 11-7085 and DAPT significantly decreased the cell proliferation OVCAR-3. IkappaB-alpha and Hes-1 mRNA levels decreased to 5 or 3% and 6% or 2% after treatment with Bay 11-7085 or DAPT, respectively (p<0.05). We also found that combination treatment exert a more potent effects on the expression of these gene (p<0.05). Moreover, siRNA transfection caused a significant reduction in IkappaB-alpha and Hes-1 mRNA levels (p<0.05). In the protein level, OVCAR-3 cell treatment with both chemichal inhibitors and specific siRNA cause a significant decrease in the expression of target genes (p<0.05) Conclusion: Our findings suggest that inhibition of NF kappaB and Notch signaling pathways can effectively reduce OVCAR-3 cells proliferation. Therefore, pharmacological targeting of the NF-kappaB and Notch signaling pathway could be a promising future treatment of ovarian cancer. PMID- 27684193 TI - EPA Method 1615. Measurement of Enterovirus and Norovirus Occurrence in Water by Culture and RT-qPCR. II. Total Culturable Virus Assay. AB - A standardized method is required when national studies on virus occurrence in environmental and drinking waters utilize multiple analytical laboratories. The U.S Environmental Protection Agency's (USEPA) Method 1615 was developed with the goal of providing such a standard for measuring Enterovirus and Norovirus in these waters. Virus is concentrated from water using an electropositive filter, eluted from the filter surface with beef extract, and then concentrated further using organic flocculation. Herein we present the protocol from Method 1615 for filter elution, secondary concentration, and measurement of total culturable viruses. A portion of the concentrated eluate from each sample is inoculated onto ten replicate flasks of Buffalo Green Monkey kidney cells. The number of flasks demonstrating cytopathic effects is used to quantify the most probable number (MPN) of infectious units per liter. The method uses a number of quality controls to increase data quality and to reduce interlaboratory and intralaboratory variation. Laboratories must meet defined performance standards. Method 1615 was evaluated by examining virus recovery from reagent-grade and ground waters seeded with Sabin poliovirus type 3. Mean poliovirus recoveries with the total culturable assay were 111% in reagent grade water and 58% in groundwaters. PMID- 27684195 TI - Ring Expansion of Donor-Acceptor Cyclopropane via Substituent Controlled Selective N-Transfer of Oxaziridine: Synthetic and Mechanistic Insights. AB - A distinctive N-substituent controlled electrophilic N-transfer of oxaziridines with donor-acceptor cyclopropanes in the presence of MgI2 is reported. Contrary to earlier reports, the oxaziridine having bulkier N-substituents can also give N transferred product instead of the O-transferred one. Interestingly, the oxaziridines having alpha-H containing N-substituents lead to the pyrrolidine derivatives through [3 + 2] cycloaddition. A mechanistic reasoning for this divergent reactivity is depicted by density functional theory calculations and validated through energy decomposition analysis. PMID- 27684194 TI - Ferric Chloride-induced Murine Thrombosis Models. AB - Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and chronic autoimmune rheumatologic disorders. Thrombi are the cause of most heart attacks, strokes and extremity loss, making thrombosis an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation and subsequent coagulation, targeting these systems therapeutically has important clinical significance for developing safer treatments. Due to the complexities of the hemostatic system, in vitro experiments cannot replicate the blood-to-vessel wall interactions; therefore, in vivo studies are critical to understand pathological mechanisms of thrombus formation. To this end, various thrombosis models have been developed in mice. Among them, ferric chloride (FeCl3) induced vascular injury is a widely used model of occlusive thrombosis that reports platelet activation and aggregation in the context of an aseptic closed vascular system. This model is based on redox induced endothelial cell injury, which is simple and sensitive to both anticoagulant and anti-platelets drugs. The time required for the development of a thrombus that occludes blood flow gives a quantitative measure of vascular injury, platelet activation and aggregation that is relevant to thrombotic diseases. We have significantly refined this FeCl3-induced vascular thrombosis model, which makes the data highly reproducible with minimal variation. Here we describe the model and present representative data from several experimental set ups that demonstrate the utility of this model in thrombosis research. PMID- 27684196 TI - Novel Production Protocol for Small-scale Manufacture of Probiotic Fermented Foods. AB - A novel dried bacterial consortium of Lactobacillus rhamnosus yoba 2012 and Streptococcus thermophilus C106 is cultured in 1 L of milk. This fresh starter can be used for the production of fermented milk and other fermented foods either at home or at small-scale in rural settings. For the fresh starter, 1 L of milk is pasteurized in a pan that fits into a larger pan containing water, placed on a source of heat. In this water bath, the milk is heated and incubated at 85 degrees C for 30 min. Thereafter, the milk is cooled down to 45 degrees C, transferred to a vacuum flask, inoculated with the dried bacteria and left for at least 16 hr between 30 degrees C and 45 degrees C. For the purpose of frequent home production, the fresh starter is frozen into ice cubes, which can be used for the production of small volumes of up to 2 L of fermented milk. For the purpose of small-scale production in resource-poor countries, pasteurization of up to 100 L of milk is conducted in milk cans that are placed in a large sauce pan filled with water and heated on a fire at 85 degrees C for 30 min, and subsequently cooled to 45 degrees C. Next, the 100 L batch is inoculated with the 1 L freshly prepared starter mentioned before. To assure an effective fermentation at a temperature between 30 and 45 degrees C, the milk can is covered with a blanket for 12 hr. For the production of non-dairy fermented foods, the fresh starter is left in a cheese cloth for 12 hr, and the drained-off whey can be subsequently used for the inoculation of a wide range of food raw materials, including vegetables and cereal-based foods. PMID- 27684197 TI - Improving the Intracellular Drug Concentration in Lung Cancer Treatment through the Codelivery of Doxorubicin and miR-519c Mediated by Porous PLGA Microparticle. AB - Porous PLGA microparticle for the coencapsulation of doxorubicin and miR-519c was successfully constructed through the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. It has been characterized with high porous surface, adaptive aerodynamic diameter (<10 MUm), favorable drug loading, and sustained release profile. The release supernatant exhibited a higher inhibition of cell proliferation than those from porous PLGA microparticles harboring a single component (doxorubicin or miR-519c), attributing to the enhanced induction of cell apoptosis and cell cycle arrest at S phase. Finally, the improved intracellular concentration of doxorubicin was elucidated by flow cytometry and liquid chromatography with tandem mass spectrometry, owing to the knockdown of drug transporter ABCG2 by miR-519c. Overall, the porous PLGA microparticle combining chemotherapy and gene therapy could facilitate the antitumor efficacy and reduce the side effects, and thus, it is potential to be used as a sustained release system for lung cancer treatment via pulmonary administration. PMID- 27684199 TI - The Penetrated Delivery of Drug and Energy to Tumors by Lipo-Graphene Nanosponges for Photolytic Therapy. AB - Delivery of drug and energy within responsive carriers that effectively target and accumulate in cancer cells promises to mitigate side effects and to enhance the uniquely therapeutic efficacy demanded for personalized medicine. To achieve this goal, however, these carriers, which are usually piled up at the periphery of tumors near the blood vessel, must simultaneously overcome the challenges associated with low tumor penetration and the transport of sufficient cargos to deep tumors to eradicate whole cancer cells. Here, we report a sponge-like carbon material on graphene nanosheet (graphene nanosponge)-supported lipid bilayers (lipo-GNS) that doubles as a photothermal agent and a high cargo payload platform and releases a burst of drug/energy (docetaxel (DTX) and gasified perfluorohexane (PFH)) and intense heat upon near-infrared irradiation. Ultrasmall lipo-GNS (40 nm) modified with a tumor-targeting protein that penetrates tumor spheroids through transcytosis exhibited a 200-fold increase in accumulation relative to a 270 nm variant of the lipo-GNS. Furthermore, a combination of therapeutic agents (DTX and PFH) delivered by lipo-GNS into tumors was gasified and released into tumor spheroids and successfully ruptured and suppressed xenograft tumors in 16 days without distal harm when subjected to a single 10 min near-infrared laser treatment. Moreover, no tumor recurrence was observed over 60 days post treatment. This sophisticated lipo-GNS is an excellent delivery platform for penetrated, photoresponsive, and combined gasification/chemo-thermotherapy to facilitate tumor treatment and for use in other biological applications. PMID- 27684200 TI - Identification of the First Elementary Step in the Photocatalytic Reduction of Nitrobenzenethiols on a Metallic Surface. AB - Reduction of nitrobenzene is widely used for the assessment of the catalytic activities of nanoparticles, yet its mechanism is still largely unverified. Here, using the surface-enhanced Raman scattering (SERS), we have identified an intermediate of the first step in the photocatalytic reduction of nitrobenzenethiols (NBTs) on a metallic surface. The formation of the intermediate is identified by a fast red-shift of the NO2 symmetric-stretching peak of the SERS spectra of reacting NBTs, prior to the slow intensity decay. On the basis of the laser power dependences of the rates of spectral changes, electrochemical SERS, and quantum chemical calculations, we conclude that the intermediate is the anion radical of nitrobenzenethiol that is formed by the metal-to-molecule single-electron transfer reaction. The subsequent intensity decay of the peak, which is the rate-determining step of the whole reduction reaction, corresponds to another single-electron reduction of the anion radical into dihydroxyaminobenzenethiol or dianion of NBT. PMID- 27684198 TI - A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication. AB - Understanding the early heterotypic interactions between cancer cells and the surrounding non-cancerous stroma is important in elucidating the events leading to stromal activation and establishment of the tumor microenvironment (TME). Several in vitro and in vivo models of the TME have been developed; however, in general these models do not readily permit isolation of individual cell populations, under non-perturbing conditions, for further study. To circumvent this difficulty, we have employed an in vitro TME model using a cell growth substrate consisting of a permeable microporous membrane insert that permits simple generation of highly enriched cell populations grown intimately, yet separately, on either side of the insert's membrane for extended co-culture times. Through use of this model, we are capable of generating greatly enriched cancer-associated fibroblast (CAF) populations from normal diploid human fibroblasts following co-culture (120 hr) with highly metastatic human breast carcinoma cells, without the use of fluorescent tagging and/or cell sorting. Additionally, by modulating the pore-size of the insert, we can control for the mode of intercellular communication (e.g., gap-junction communication, secreted factors) between the two heterotypic cell populations, which permits investigation of the mechanisms underlying the development of the TME, including the role of gap-junction permeability. This model serves as a valuable tool in enhancing our understanding of the initial events leading to cancer-stroma initiation, the early evolution of the TME, and the modulating effect of the stroma on the responses of cancer cells to therapeutic agents. PMID- 27684201 TI - Phage-Mediated Immuno-PCR for Ultrasensitive Detection of Cry1Ac Protein Based on Nanobody. AB - The widespread use of Cry proteins in transgenic plants for insect control has raised concerns about the environment and food safety in the public. An effective detection method for introduced Cry proteins is of significance for environmental risk assessment and product quality control. This paper describes a novel phage mediated immuno-PCR (iPCR) for the ultrasensitive determination of Cry proteins based on nanobodies. Three nanobodies against Cry1Ac protein were obtained from a naive phage displayed nanobody library without animal immunization process and were applied to the iPCR assay for Cry1Ac. The phage-mediated iPCR for Cry1Ac based on nanobodies showed a dynamic range of 0.001-100 ng/mL and a limit detection of 0.1 pg/mL. Specific measurement of this established method was performed by testing cross-reativity of other Cry1Ac analogues, and the result showed negligible cross-reactivity with other test Cry proteins (Cry1Ab, Cry1F, Cry3B). Furthermore, the phage-mediated iPCR based on nanobody should be easily applicable to the detection of many other Cry proteins. PMID- 27684202 TI - Curacin E from the Brittle Star Ophiocoma scolopendrina. AB - Bioassay-guided fractionation of the extract of the brittle star Ophiocoma scolopendrina afforded curacin E (1), a congener of curacin A (2). Curacin A (2) is an antimitotic agent of cyanobacterial origin. The structure of curacin E was studied by interpretation of NMR data and the ECD spectrum. Curacin E has an ethylcarbonyl terminus in its side chain and inhibits the proliferation of P388 cells. PMID- 27684203 TI - How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases. AB - Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed. PMID- 27684205 TI - Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells. AB - A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in which the liver has been repopulated with functional human hepatocytes, could serve as a useful tool for investigating human hepatic cell biology, drug metabolism, and other preclinical applications. One of the key factors required for successful transplantation of human hepatocytes into mice is the elimination of the endogenous hepatocytes to prevent competition with the human cells and provide a suitable space and microenvironment for promoting human donor cell expansion and differentiation. To date, two major liver injury mouse models utilizing fumarylacetoacetate hydrolase (Fah) and uroplasminogen activator (uPA) mice have been established. However, Fah mice are used mainly with mature hepatocytes and the application of the uPA model is limited by decreased breeding. To overcome these limitations, Alb-toxin receptor mediated cell knockout (TRECK)/SCID mice were used for in vivo differentiation of immature human hepatocytes and humanized liver generation. Human hepatic stem cells (HpSCs) successfully repopulated the livers of Alb-TRECK/SCID mice that had developed lethal fulminant hepatic failure following diphtheria toxin (DT) treatment. This model of a humanized liver in Alb TRECK/SCID mice will have functional applications in studies involving drug metabolism and drug-drug interactions and will promote other in vivo and in vitro studies. PMID- 27684206 TI - Antibacterial efficacy of silver nanoparticles synthesized employing Terminalia arjuna bark extract. AB - In the present investigation, we have explored simple, robust, inexpensive, and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using Terminalia arjuna bark extract (TA-AgNPs). Various parameters dictating the biosynthesis of TA-AgNPs such as time and temperature of reaction, concentration of AgNO3, and T. arjuna extract amount were investigated. Characterization of TA AgNPs was done via UV-vis spectroscopy along with FT-IR, XRD, SEM and dynamic light scattering. The antimicrobial activity of TA-AgNPs was investigated against Escherichia coli. Comparable zone of inhibition was exhibited by TA-AgNPs. This study suggests that TA-AgNPs possesses significant antibacterial properties. PMID- 27684207 TI - On the Occasion of an Important Anniversary. PMID- 27684204 TI - Community-wide outbreak of haemolytic uraemic syndrome associated with Shiga toxin 2-producing Escherichia coli O26:H11 in southern Italy, summer 2013. AB - In summer 2013, an excess of paediatric cases of haemolytic uraemic syndrome (HUS) in a southern region of Italy prompted the investigation of a community wide outbreak of Shiga toxin 2-producing Escherichia coli (STEC) O26:H11 infections. Case finding was based on testing patients with HUS or bloody diarrhoea for STEC infection by microbiological and serological methods. A case control study was conducted to identify the source of the outbreak. STEC O26 infection was identified in 20 children (median age 17 months) with HUS, two of whom reported severe neurological sequelae. No cases in adults were detected. Molecular typing showed that two distinct STEC O26:H11 strains were involved. The case-control study showed an association between STEC O26 infection and consumption of dairy products from two local plants, but not with specific ready to-eat products. E.coli O26:H11 strains lacking the stx genes were isolated from bulk milk and curd samples, but their PFGE profiles did not match those of the outbreak isolates. This outbreak supports the view that infections with Stx2 producing E. coli O26 in children have a high probability of progressing to HUS and represent an emerging public health problem in Europe. PMID- 27684209 TI - The ability of an electrocardiogram to predict fatal and non-fatal cardiac events in asymptomatic middle-aged subjects. AB - INTRODUCTION: The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. MATERIALS AND METHODS: A total of 9511 middle-aged subjects (mean age 43 +/- 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. RESULTS: Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1-2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1-1.5, p < 0.001). Model discrimination measured with the C-index showed only a minor improvement with the inclusion of ECG abnormalities: 0.851 versus 0.853 and 0.742 versus 0.743 for 10- and 30-year follow-up, respectively. ECG did not predict non fatal cardiac events after 10-years or 30-years of follow-up. DISCUSSION: Major ECG abnormalities are associated with an increased risk of short and long-term cardiac mortality in middle-aged subjects. However, the improvement in discrimination between subjects with and without fatal cardiac events was marginal with abnormal ECG. KEY MESSAGES: Abnormalities observed on 12-lead electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects. PMID- 27684210 TI - In vitro assessment of the roles of drug transporters in the disposition and drug drug interaction potential of olaparib. AB - 1. In vitro assessments were conducted to examine interactions between olaparib (a potent oral inhibitor of poly[ADP-ribose] polymerase) and drug transporters. 2. Olaparib showed inhibition of the hepatic drug uptake transporters OATP1B1 (IC50 values of 20.3 MUM and 27.1 MUM) and OCT1 (IC50 37.9 MUM), but limited inhibition of OATP1B3 (25% at 100 MUM); inhibition of the renal uptake transporters OCT2 (IC50 19.9 MUM) and OAT3 (IC50 18.4 MUM), but limited inhibition of OAT1 (13.5% at 100 MUM); inhibition of the renal efflux transporters MATE1 and MATE2K (IC50s 5.50 MUM and 47.1 MUM, respectively); inhibition of the efflux transporter MDR1 (IC50 76.0 MUM), but limited inhibition of BCRP (47% at 100 MUM) and no inhibition of MRP2. At clinically relevant exposures, olaparib has the potential to cause pharmacokinetic interactions via inhibition of OCT1, OCT2, OATP1B1, OAT3, MATE1 and MATE2K in the liver and kidney, as well as MDR1 in the liver and GI tract. Olaparib was found to be a substrate of MDR1 but not of several other transporters. 3. Our assessments indicate that olaparib is a substrate of MDR1 and may cause clinically meaningful inhibition of MDR1, OCT1, OCT2, OATP1B1, OAT3, MATE1 and MATE2K. PMID- 27684211 TI - Can probation officers identify remorse among male adolescent offenders? AB - Judgments about a youth's level of remorse are frequently used to make important decisions in the juvenile justice system that can have serious consequences to the person. Unfortunately, little is known about these ratings and what factors may influence them. In a sample of 325 1st-time youth offenders who were arrested for offenses of moderate severity, we tested whether probation officers' ratings of an adolescent's remorse soon after arrest were associated with the youth's self-report of showing a callous and unemotional interpersonal style, being arrested for a violent offense, and several demographic and background characteristics (e.g., age, race, socioeconomic status [SES], and intelligence). Our analyses indicated that both arrest for a violent offense and the adolescent's self-reported level of callous-unemotional (CU) traits were associated with probation officers' ratings of remorse. Further, youth age, SES, and intelligence neither were associated with these judgments nor moderated the association between CU traits and probation officers' ratings of remorse. However, youth race or ethnicity did moderate the association between CU traits and judgments of remorse, such that Latino youth who were high on CU traits showed a very low probability of being rated as remorseful. (PsycINFO Database Record PMID- 27684212 TI - Bactericidal, quorum quenching and anti-biofilm nanofactories: a new niche for nanotechnologists. AB - Despite several conventional potent antibacterial therapies, bacterial infections pose a significant threat to human health because they are emerging as the leading cause of death worldwide. Due to the development of antibiotic resistance in bacteria, there is a pressing demand to discover novel approaches for developing more effective therapies to treat multidrug-resistant bacterial strains and biofilm-associated infections. Therefore, attention has been especially devoted to a new and emerging branch of science "nanotechnology" to design non-conventional antimicrobial chemotherapies. A range of nanomaterials and nano-sized carriers for conventional antimicrobial agents have fully justified their potential to combat bacterial diseases by reducing cell viability, by attenuating quorum sensing, and by inhibiting/or eradicating biofilms. This communication summarizes emerging nano-antimicrobial therapies in treating bacterial infections, particularly using antibacterial, quorum quenching, and anti-biofilm nanomaterials as new approaches to tackle the current challenges in combating infectious diseases. PMID- 27684213 TI - It just feels weird!: a qualitative study of how children aged 10-18 years describe neuropathic pain. AB - PURPOSE: The aim of this study was to explore how children aged 10-18 years describe their neuropathic pain (NP). METHOD: This is a qualitative descriptive study using inductive content analysis. Semi-structured interviews were conducted with eight children, aged 10-18 years with varying diagnoses, who were experiencing NP. RESULTS: All children were able to describe their NP using a variety of strategies, including use of literal and figurative language. While some sensory descriptors commonly reported by adults were used, descriptions of NP pattern and impact were also integral to their narratives. Children were able to differentiate NP from nociceptive pain. Parents clarified and gave context to pain reports. CONCLUSIONS: NP is a complex experience necessitating consideration of the different ways that children describe their symptoms. Involvement of parents is invaluable to the process of taking a pain history with a child who is being screened for NP. Implications for Rehabilitation The findings of the study may inform the screening process for NP in children to facilitate earlier identification. Clinicians should consider the variety of ways that children may express their NP symptoms and the resulting impact. Clinicians should probe further when children report that symptoms are hard to describe or "weird". Presence of a parent during the child's pain assessment may assist with gathering a more complete picture. PMID- 27684214 TI - What has passed is prolog: new cellular and physiological roles of G6PD. AB - G6PD deficiency has been the most pervasive inherited disorder in the world since having been discovered. G6PD has an antioxidant role by functioning as a major nicotinamide adenine dinucleotide phosphate (NADPH) provider to reduce excessive oxidative stress. NADPH can produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) mediated by NADPH oxidase (NOX) and nitric oxide synthase (NOS), respectively. Hence, G6PD also has a pro-oxidant role. Research in the past has focused on the enhanced susceptibility of G6PD-deficient cells or individuals to oxidative challenge. The cytoregulatory role of G6PD has largely been overlooked. By using a metabolomic approach, it is noted that upon oxidant challenge, G6PD-deficient cells will reprogram the GSH metabolism from regeneration to synthesis with exhaustive energy consumption. Recently, new cellular/physiologic roles of G6PD have been discovered. By using a proteomic approach, it has been found that G6PD plays a regulatory role in xenobiotic metabolism possibly via NOX and the redox-sensitive Nrf2-signaling pathway to modulate the expression of xenobiotic-metabolizing enzymes. Since G6PD is a key regulator responsible for intracellular redox homeostasis, G6PD deficiency can alter redox balance leading to many abnormal cellular effects such as the cellular inflammatory and immune response against viral infection. G6PD may play an important role in embryogenesis as G6PD-knockdown mouse cannot produce offspring and G6PD-deficient C. elegans with defective egg production and hatching. This array of findings indicates that the cellular and physiologic roles of G6PD, other than the classical role as an antioxidant enzyme, deserve further attention. PMID- 27684215 TI - Philosophical reflections on the mission of the European College of Sport Science: Challenges and opportunities. AB - The European College of Sport Science (ECSS) was established in part to promote the integrated study of sports and related phenomena from multi- and interdisciplinary perspectives. There are significant and enduring philosophical, epistemological and professional challenges and opportunities that arise from this integrationist perspective. In this article, we reflect upon the challenges that have arisen in the development of sport sciences in the attempt to realize the ECSS mission. We identify three paradigmatic approaches to sports science: (1) the mechanistic; (2) the hermeneutic and (3) the critical. We critically evaluate these paradigms and their potential within the broad framework of integrationist ambitions for sports science as a scientific field. PMID- 27684217 TI - ? AB - Virginia Bottomley and Stephen Dorrell switched roles last week. The job swap couldn't have been more timely, with the health department stuck in the now protracted pay dispute and the looming prospect of yet more discontent with GPs over 'out of hours' payments. A new face at the top of the department could certainly signal some movement on both fronts. PMID- 27684218 TI - ? AB - Anne Picking, chair of Unison's health sector, at the launch of her union's latest poster campaign. PMID- 27684216 TI - The role of older siblings in the sexual and reproductive health of Mexican origin young women in immigrant families. AB - In the USA, young people of Mexican-origin are more economically disadvantaged and experience higher birth rates than many other Latino groups. In this paper, we examine the influence of older siblings on the sexual and reproductive health of Mexican-origin immigrant women. Qualitative data were drawn from life history interviews with 21 first- and second-generation Mexican-origin women, aged 27-41 years old, resident in the Metro Denver area. Data suggest that older siblings may protect younger sisters from risky sexual behaviours through older siblings' responsibility and care for younger siblings, close and supportive sibling relationships, older siblings' advice about both sexual health and academic success, and sibling modelling. These mechanisms appear particularly protective due to the social and economic hardships immigrant families often face. Implications include fostering healthy sibling relationships and involving older siblings more fully in the sexuality education of younger siblings. PMID- 27684219 TI - Appointment of Dorrell welcomed. AB - Nursing unions have welcomed the replacement of Virginia Bottomley by Stephen Dorrell as health secretary. PMID- 27684220 TI - RB posts set to face Nolan test. AB - New ways of appointing members of the nurses' pay Review Body are being considered by the government in a bid to ensure the system is as stringent as possible. PMID- 27684222 TI - RCN accuses Unison of smear campaign. AB - The RCN has accused some Unison stewards of attempting to smear the College in pay campaign leaflets which it has called 'a dossier of shame'. PMID- 27684221 TI - Hancock urges Dorrell to set deadline for no-offer trusts. AB - The Royal College of Nursing has written to new health secretary Stephen Dorrell urging him to set a final deadline of August 9 for the 41 trusts who have not yet made pay offers. PMID- 27684223 TI - Widespread criticism of league tables. AB - The government published its second set of hospital league tables last week amid wide criticism from nursing unions and opposition parties, who said they failed to take into account quality of care. PMID- 27684224 TI - Initiative on young people's health welcomed by unions. AB - The health of young people is the focus of a new government initiative launched last week by former health secretary Virginia Bottomley. PMID- 27684225 TI - Clinical supervision 'fundamental'. AB - Nurses need to convince managers that clinical supervision is fundamental to the future of nursing practice and nurses' personal development, chief nursing officer Yvonne Moores said last week. PMID- 27684226 TI - DoH approves launch of guidelines. AB - The health department has approved the launch of the first in a series of clinical guidelines for cost-effective practice. PMID- 27684227 TI - Major drive to help reduce hospital-acquired infections. AB - New research showing nearly one in ten of all inpatients in acute hospitals become infected after admission is set to lead to a major government drive aimed at reducing hospital- acquired infections. PMID- 27684228 TI - Protecting the nurse's right to whistleblow. AB - The UK Central Council has called on purchasers and providers to write into nurses' contracts the right to blow the whistle if they have concerns about care standards. PMID- 27684229 TI - RCN issues writs to pension firms. AB - The RCN has issued more than 20 writs against life assurance companies for mis selling personal pensions to nurses. PMID- 27684231 TI - The fight for our profession. AB - American nursing is facing its greatest threat ever as individual states attempt to implement healthcare changes following the collapse of President Bill Clinton's federal-wide health reforms, the American Nurses' Association's house of delegates heard last week. PMID- 27684232 TI - ? AB - Coretta Scott King (centre), widow of 1960s civil rights campaigner Martin Luther King, was a guest speaker at a special fund-raising dinner in support of a new campaign 'Nurses Challenge Violence'. Hillary Clinton sent a special message to the American Nurses' Foundation dinner saying she hoped the campaign would 'resonate throughout the nation and encourage others to participate'. Also pictured are the ANA's president, Virginia Trotter Betts (right), and executive director, Geri Marullo. PMID- 27684233 TI - Division over degree-based nurse education. AB - The conference was divided on the issue of implementing degree-based nurse education, with many delegates stressing that funding and access to baccalaureate nursing degrees was limited. PMID- 27684234 TI - A 'single payer' mechanism for health funding is endorsed. AB - The concept of a 'single payer' mechanism for funding health care was given overwhelming endorsement by the ANA, with the rider that other funding schemes should not be ruled out. PMID- 27684235 TI - ENB to scrap student/teacher ratios. AB - Recent proposals made by the English National Board to stop recommending a ratio of staff to students in regulations for approving nursing and midwifery courses received harsh criticism from UKCC council last week. PMID- 27684236 TI - References to be put under review. AB - Character references are causing concern among student practitioners and principals of nurse and midwifery education institutions, Council heard last week. PMID- 27684237 TI - Employers get PREP requirements wrong. AB - Enrolled nurses are being wrongly informed by their employers that they have to convert to registered nurse status in order to meet the UKCC's post-registration education and practice (PREP) requirements, the Council heard last week. PMID- 27684238 TI - Practice-based general nurse 'not in interests of public safety', says Council. AB - A generalist practice nurse cannot perform the combined roles of a health visitor, district nurse and community psychiatric nurse, UKCC member Alison Norman claimed at the meeting last week. PMID- 27684239 TI - Resistance to paying for travel vaccines. AB - Many patients would forgo travel vaccination if they had to pay more than a standard prescription charge for it, according to recently published research. PMID- 27684240 TI - Women get raw deal in angina investigation. AB - Women get raw deal in angina investigation Women with treated angina are half as likely as men to be referred for hospital investigation, although the severity of their angina is similar. PMID- 27684241 TI - HPV testing improves cervical screening. AB - Testing for human papilloma virus (HPV) might be a useful adjunct to routine cervical cytology in young women, according to new research. PMID- 27684242 TI - Suspect laundry in infection outbreaks. AB - Infection control teams should take laundering services very seriously in outbreaks that seem to have no obvious cause. PMID- 27684243 TI - Auxiliaries have a very valuable role. AB - With reference to the article 'Qualified nurses under threat from NVQs?' (Viewpoint June 21), I would point out that a nursing home is, after all, a home for clients who need a service. If this service is, in the main, provided by just one person, who may eventually become a friend and confidant, then surely this is less confusing to an elderly person. PMID- 27684244 TI - Keep supervision issues separate. AB - Your recent coverage on clinical supervision 'Introducing clinical supervision: a guide' (Clinical, June 28) has provided a good insight into the difficulties of introducing it to our work settings. It is this implementation which has been a real concern to mental health groups in the Royal College of Nursing. PMID- 27684245 TI - Not everyone shuns P2000 students. AB - I was saddened to read of Neil Starkie's experience of negative attitudes towards Project 2000 students (Viewpoint June 28), but would like to reassure him that not all 'traditionally trained' nurses view them its incompetent. PMID- 27684246 TI - Who is really in cloud cuckoo land? AB - I am writing in reply to Lis Hughes' letter 'Wake up! You're living in cloud cuckoo land' (Viewpoint June 28). PMID- 27684248 TI - Information exchange. AB - I am a third year student nurse writing my final summative essay entitled 'Improving the role of the nurse in the nutritional support of hospitalised patients aged 18 + '. I would appreciate any notes concerning the history of the nutrition nurse specialist. PMID- 27684247 TI - No need to feel threatened by NVQs. AB - Qualified nurses should not feel threatened by NVQs in care. Carol Dimon (Viewpoint June 21) rightly states that qualified nurses are trained to national standards. Well so are NVQ candidates. They have a Care qualification. PMID- 27684249 TI - Is quality being sold out to economy? AB - I am becoming increasingly worried about trends in the award of contracts for nursing education courses. PMID- 27684250 TI - Readers panel - Should wards be single sex? AB - Our experts consider a hot topic of the day. PMID- 27684252 TI - New this month. PMID- 27684251 TI - The spirit of care David Stoter M Mosby L9.95 168pp 0-723-41955-8 0723419558 [Formula: see text]. AB - What constitutes spiritual care? This question has been the subject of much discussion in recent years. While it is generally accepted that meaningful care has to cater for the whole person, there is great confusion over what constitutes spiritual care. PMID- 27684254 TI - New this month. PMID- 27684253 TI - Health and Culture:beyond the Western Paradigm Health and Culture:beyond the Western Paradigm O Collins Airhihenbuwa SAGE 152pp L15.50 0-8039-7157-5 0803971575 [Formula: see text]. AB - No doubt there is an increasing need for nursing texts which explain how health and illness are viewed from non-Western viewpoints. Anyone who has experienced severe illness in a vastly foreign culture will know how alarmingly disorientating it can be. PMID- 27684255 TI - Social caring The Individual in Society Bob Hallawell and Richard Brittle Scutari Press 227pp L14.99 1-871364-99-X 187136499X [Formula: see text]. AB - So now we are all holistic practitioners, and never again will anybody be referred to as 'the kidney in bed seven'. Everyone slips up sometimes, however, and this book aims to help establish a sociological grounding among P2000 common foundation students in the wider aspects of health care. PMID- 27684256 TI - Life Changes: Conversations, Stories and Poems Life Changes: Conversations, Stories and Poems Action Factory Community Arts L3 93pp 1-899-30010-4 1899300104. AB - You could read this book easily inside 35 minutes, if you were a compulsive devourer of people's anecdotes. Life Changes is a fascinating collection of life events and memories, based on interviews with more than 2,000 residents in CrestaCare homes in England, the Isle of Man and Northern Ireland. PMID- 27684257 TI - Ethical foundations of health care Jane Singleton Ethical foundations of health care Susan McLaren Mushy 202pp L9-95 0-7234-1873-X 072341873X. AB - If you ever considered ethics a dry subject, then this book should help change your mind. The authors, Jane Singleton in particular, speak to readers from the page. In simple language, Singleton explains complex concepts, poses questions and used real-life examples to illustrate arguments. PMID- 27684258 TI - Acute medical illness in old age Alan Sinclair Acute medical illness in old age Ken Woodhouse Editors Chapman & Hall 281pp L45 (h/b) 0-412-56920-5 0412569205 [Formula: see text]. AB - The content of Acute Medical Illness in Old Age is not aimed specifically at those specialising in the care of elderly people. Other areas in which elderly people are encountered are covered and problems which need to be considered by physicians working in these areas arc described. PMID- 27684259 TI - Research appreciation: an initial guide for nurses and health care professionals Paula McGee Research appreciation: an initial guide for nurses and health care professionals Joy Notter Qnay Books 149pp L11 -95 1-85642-026-4 1856420264. AB - When writing an introductory book on any subject, a balance has to be struck between simplicity and complexity. This text moves uncomfortably between the two. PMID- 27684260 TI - New this month. PMID- 27684261 TI - Understanding nursing research Nancy burns and Susan grove WB Saunders Understanding nursing research nancy burns and susan grove 585pp L20 0-7216-4436 8 0721644368 [Formula: see text]. AB - This is an excellent resource book on nursing research and readers should not be deterred by the fact that it is written by two American professors. It is packed with interesting and informative discussion on all aspects of research. PMID- 27684262 TI - Survey doubts. AB - Do patient satisfaction surveys really tell the whole story? In the light of doubts about the validity of conventional survey methods, Nottingham University has launched a new Nursing Policy Studies publication outlining a less structured, more interview-based approach to patients' views about outpatient services. PMID- 27684264 TI - Cardiology ROM. AB - I Healthcare students can now learn about cardiology using the latest CD-Rom teaching technology. PMID- 27684263 TI - HRT conspiracy? AB - Is hormone replacement therapy a conspiracy? Author Sandra Coney claims in her book The Menopause Industry that menopausal women are being targeted by drugs companies and the medical profession to create a new growth industry. PMID- 27684266 TI - New this month. PMID- 27684265 TI - Assessing patients. AB - A new American video on assessing patients 'head-to- toe' has been launched by the Springhouse Corporation. PMID- 27684267 TI - Galling video. AB - Patients can get a televised preview of their own gallbladder operations, thanks to a new video, narrated by Tomorrow's World presenter, Judith Hann. PMID- 27684268 TI - Age Concern update. AB - Age Concern has released updated second editions of two books explaining the impact of HIV and AIDS on older people. A Crisis of Silence - HIV, AIDS and Older People sets out comprehensive recommendations for caring professionals working with older people. The latest edition, priced L5, contains new facts and figures on the numbers of older people affected by HIV and AIDS. PMID- 27684269 TI - Listings. AB - As there is such a huge demand for the publication of free listings, readers may wish to take advantage of a new service being launched by Nursing Standard. For further details please see the coupon on page 69 or contact Veronica Brown, telephone 0181 423 1066. PMID- 27684270 TI - The expanding role of the bile acid receptor farnesoid X in the intestine and its potential clinical implications. AB - Knowledge about the role of farnesoid X receptor (FXR) in the intestine is rapidly expanding. In pre-clinical animal models of inflammatory bowel disease and bile duct ligation, FXR activation has proven to directly target the three pillars of intestinal homeostasis: intestinal permeability, inflammation and bacterial translocation. The protective role of FXR-ligands on this homeostasis has implications for many intestinal pathologies like inflammatory bowel disease, ischemia reperfusion injury, the metabolic syndrome, colon cancer and even diarrhea. In this review, we summarize the mechanisms by which FXR-activation exerts these protective effects and we discuss its potential clinical applications. PMID- 27684272 TI - Varicella prevention - a lifelong and challenging affair. PMID- 27684271 TI - Facial reanimation using hypoglossal-facial nerve anastomosis after schwannoma removal. AB - CONCLUSION: In this series, the split type hypoglossal-facial nerve anastomosis resulted in more favorable outcomes in terms of both facial function and tongue atrophy. OBJECTIVE: This study compared surgical techniques for hypoglossal facial nerve anastomosis after schwannoma removal and evaluated which technique achieves better facial outcomes and less tongue morbidity. METHOD: This study included 14 patients who underwent hypoglossal-facial nerve anastomosis after schwannoma removal and were followed for more than 1 year. Three surgical techniques were performed: end-to-end, end-to-side, and split anastomoses. Facial palsy and tongue atrophy after anastomosis were evaluated using the scales suggested by House-Brackmann and Martins, respectively. Tumor volume and the time to surgery were also evaluated, and the effects on facial outcomes were analyzed. RESULTS: Overall, nine of 14 (64.3%) patients had favorable facial outcomes, and eight of 14 (57.1%) had favorable tongue outcomes. Regarding facial palsy, five of seven (71.4%) end-to-end, three of four (75%) split, and only one of three (33.3%) end-to-side patients had favorable facial function. Regarding tongue atrophy, all three (100%) end-to-side, three of four (75%) split, and two of seven (28.6%) end-to-end patients had favorable tongue outcomes. The effects of tumor volume and time to surgery on facial outcome were not significant. PMID- 27684273 TI - Efficient Sporulation of Saccharomyces cerevisiae in a 96 Multiwell Format. AB - During times of nutritional stress, Saccharomyces cerevisiae undergoes gametogenesis, known as sporulation. Diploid yeast cells that are starved for nitrogen and carbon will initiate the sporulation process. The process of sporulation includes meiosis followed by spore formation, where the haploid nuclei are packaged into environmentally resistant spores. We have developed methods for the efficient sporulation of budding yeast in 96 multiwell plates, to increase the throughput of screening yeast cells for sporulation phenotypes. These methods are compatible with screening with yeast containing plasmids requiring nutritional selection, when appropriate minimal media is used, or with screening yeast with genomic alterations, when a rich presporulation regimen is used. We find that for this method, aeration during sporulation is critical for spore formation, and have devised techniques to ensure sufficient aeration that are compatible with the 96 multiwell plate format. Although these methods do not achieve the typical ~80% level of sporulation that can be achieved in large volume flask based experiments, these methods will reliably achieve about 50-60% level of sporulation in small-volume multiwell plates. PMID- 27684274 TI - Utility of Macrophage-activated Marker CD163 for Diagnosis and Prognosis in Pulmonary Tuberculosis. AB - RATIONALE: Among infectious diseases, tuberculosis (TB) is a leading cause of death worldwide. Accumulated knowledge has revealed that macrophages are deeply involved in the progression and pathogenesis of TB. We hypothesized that the evaluation of a macrophage activation marker may be useful in the diagnosis and assessment of pulmonary TB. OBJECTIVES: To examine the utility of the macrophage activation marker soluble CD163 (sCD163) as a diagnostic tool and measure of disease severity for pulmonary TB and tuberculous pleurisy. METHODS: We compared the concentration of sCD163 in serum samples of 180 patients with active pulmonary TB with concentrations in serum samples of 45 age- and sex-matched control subjects. We also measured sCD163 in pleural fluid samples of 100 patients with pleural disease, including 31 patients with tuberculous pleurisy. MEASUREMENTS AND MAIN RESULTS: We found increased serum concentrations of sCD163 in patients with active pulmonary TB compared with those of control subjects (1,643 +/- 1,737 ng/ml vs. 533.9 +/- 49.3 ng/ml; P < 0.0001). sCD163 levels were also higher in pleural fluid samples of patients with pulmonary TB than in those of patients with non-TB pleurisy (5,239 +/- 2,436 ng/ml vs. 2,877 +/- 1,191 ng/ml; P < 0.0001). The levels of sCD163 in pleural effusions were significantly higher than serum levels obtained simultaneously from the same patients, particularly for patients with tuberculous pleurisy. Patients with a serum level of sCD163 above 1,300 ng/ml, had a mortality rate that was five times higher than that of patients with a lower sCD163 level (44.6% vs. 6.6%; P < 0.0001 by log rank test). Microscopic examination of lung and pleural tissue samples showed concordance of enhanced CD163 expression with the presence of caseating granulomas in tissue obtained from patients with TB. CONCLUSIONS: The macrophage activation marker CD163 was increased in patients with active pulmonary TB compared with age- and sex-matched control subjects. Increased levels of sCD163 were associated with increased mortality in patients with pulmonary TB. sCD163 also showed promise as a diagnostic tool for tuberculous pleurisy. These results warrant further study of sCD163 as a potentially useful biomarker for the diagnosis and assessment of pulmonary TB. Clinical trial registered with www.umin.ac.jp/ctr/index-j.htm (UMIN000003400). PMID- 27684275 TI - Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy. AB - Small RNA therapies targeting post-integration steps in the HIV-1 replication cycle are among the top candidates for gene therapy and have the potential to be used as drug therapies for HIV-1 infection. Post-integration inhibitors include ribozymes, short hairpin (sh) RNAs, small interfering (si) RNAs, U1 interference (U1i) RNAs and RNA aptamers. Many of these have been identified using transient co-transfection assays with an HIV-1 expression plasmid and some have advanced to clinical trials. In addition to measures of efficacy, small RNAs have been evaluated for their potential to affect the expression of human RNAs, alter cell growth and/or differentiation, and elicit innate immune responses. In the protocols described here, a set of transient transfection assays designed to evaluate the efficacy and toxicity of RNA molecules targeting post-integration steps in the HIV-1 replication cycle are described. We have used these assays to identify new ribozymes and optimize the format of shRNAs and siRNAs targeting HIV 1 RNA. The methods provide a quick set of assays that are useful for screening new anti-HIV-1 RNAs and could be adapted to screen other post-integration inhibitors of HIV-1 replication. PMID- 27684277 TI - Psychosocial interventions for psychostimulant misuse. AB - BACKGROUND: Psychostimulant misuse is a continuously growing medical and social burden. There is no evidence proving the efficacy of pharmacotherapy. Psychosocial interventions could be a valid approach to help patients in reducing or ceasing drug consumption. OBJECTIVES: To assess the effects of psychosocial interventions for psychostimulant misuse in adults. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive); Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Web of Science and PsycINFO, from inception to November 2015. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. SELECTION CRITERIA: We included randomised controlled trials comparing any psychosocial intervention with no intervention, treatment as usual (TAU) or a different intervention in adults with psychostimulant misuse or dependence. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included a total of 52 trials (6923 participants).The psychosocial interventions considered in the studies were: cognitive behavioural therapy (19 studies), contingency management (25 studies), motivational interviewing (5 studies), interpersonal therapy (3 studies), psychodynamic therapy (1 study), 12-step facilitation (4 studies).We judged most of the studies to be at unclear risk of selection bias; blinding of personnel and participants was not possible for the type of intervention, so all the studies were at high risk of performance bias with regard to subjective outcomes; the majority of studies did not specify whether the outcome assessors were blind. We did not consider it likely that the objective outcomes were influenced by lack of blinding.The comparisons made were: any psychosocial intervention versus no intervention (32 studies), any psychosocial intervention versus TAU (6 studies), and one psychosocial intervention versus an alternative psychosocial intervention (13 studies). Five of included studies did not provide any useful data for inclusion in statistical synthesis.We found that, when compared to no intervention, any psychosocial treatment: reduced the dropout rate (risk ratio (RR): 0.83, 95% confidence interval (CI) 0.76 to -0.91, 24 studies, 3393 participants, moderate quality evidence); increased continuous abstinence at the end of treatment (RR: 2.14, 95% CI 1.27 to -3.59, 8 studies, 1241 participants, low quality evidence); did not significantly increase continuous abstinence at the longest follow-up (RR: 2.12, 95% CI 0.77 to -5.86, 4 studies, 324 participants, low quality evidence); significantly increased the longest period of abstinence: (standardised mean difference (SMD): 0.48, 95% CI 0.34 to 0.63, 10 studies, 1354 participants, high quality evidence). However, it should be noted that the in the vast majority of the studies in this comparison the specific psychosocial treatment assessed in the experimental arm was given in add on to treatment as usual or to another specific psychosocial or pharmacological treatment which was received by both groups. So, many of the control groups in this comparison were not really untreated. Receiving some amount of treatment is not the same as not receiving any intervention, so we could argue that the overall effect of the experimental psychosocial treatment could be smaller if given in add on to TAU or to another intervention than if given to participants not receiving any intervention; this could translate to a smaller magnitude of the effect of the psychosocial intervention when it is given in add on.When compared to TAU, any psychosocial treatment reduced dropout rate (RR: 0.72, 95% CI 0.59 to 0.89, 6 studies, 516 participants, moderate quality evidence), did not increase continuous abstinence at the end of treatment (RR: 1.27, 95% CI 0.94 to 1.72, 2 studies, 224 participants, low quality evidence), did not increase longest period of abstinence (MD -3.15 days, 95% CI -10.35 to 4.05, 1 study, 110 participants, low quality evidence). No studies in this comparison assessed the outcome of continuous abstinence at longest follow-up.There were few studies comparing two or more psychosocial interventions, with small sample sizes and considerable heterogeneity in terms of the types of interventions assessed. None reported significant results.None of the studies reported harms related to psychosocial interventions. AUTHORS' CONCLUSIONS: The addition of any psychosocial treatment to treatment as usual (usually characterised by group counselling or case management) probably reduces the dropout rate and increases the longest period of abstinence. It may increase the number of people achieving continuous abstinence at the end of treatment, although this might not be maintained at longest follow up. The most studied and the most promising psychosocial approach to be added to treatment as usual is probably contingency management. However, the other approaches were only analysed in a few small studies, so we cannot rule out the possibility that the results were not significant because of imprecision. When compared to TAU, any psychosocial treatment may improve adherence, but it may not improve abstinence at the end of treatment or the longest period of abstinence.The majority of the studies took place in the United States, and this could limit the generalisability of the findings, because the effects of psychosocial treatments could be strongly influenced by the social context and ethnicity. The results of our review do not answer the most relevant clinical question, demonstrating which is the most effective type of psychosocial approach.Further studies should directly compare contingency management with the other psychosocial approaches. PMID- 27684276 TI - Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors. AB - As our understanding of the driver mutations necessary for initiation and progression of cancers improves, we gain critical information on how specific molecular profiles of a tumor may predict responsiveness to therapeutic agents or provide knowledge about prognosis. At our institution a tumor genotyping program was established as part of routine clinical care, screening both hematologic and solid tumors for a wide spectrum of mutations using two next-generation sequencing (NGS) panels: a custom, 33 gene hematological malignancies panel for use with peripheral blood and bone marrow, and a commercially produced solid tumor panel for use with formalin-fixed paraffin-embedded tissue that targets 47 genes commonly mutated in cancer. Our workflow includes a pathologist review of the biopsy to ensure there is adequate amount of tumor for the assay followed by customized DNA extraction is performed on the specimen. Quality control of the specimen includes steps for quantity, quality and integrity and only after the extracted DNA passes these metrics an amplicon library is generated and sequenced. The resulting data is analyzed through an in-house bioinformatics pipeline and the variants are reviewed and interpreted for pathogenicity. Here we provide a snapshot of the utility of each panel using two clinical cases to provide insight into how a well-designed NGS workflow can contribute to optimizing clinical outcomes. PMID- 27684278 TI - Measurements and Predictions of Binary Component Aerosol Particle Viscosity. AB - Organic aerosol particles are known to often absorb/desorb water continuously with change in gas phase relative humidity (RH) without crystallization. Indeed, the prevalence of metastable ultraviscous liquid or amorphous phases in aerosol is well-established with solutes often far exceeding bulk phase solubility limits. Particles are expected to become increasingly viscous with drying, a consequence of the plasticizing effect of water. We report here measurements of the variation in aerosol particle viscosity with RH (equal to condensed phase water activity) for a range of organic solutes including alcohols (diols to hexols), saccharides (mono-, di-, and tri-), and carboxylic acids (di-, tri-, and mixtures). Particle viscosities are measured over a wide range (10-3 to 1010 Pa s) using aerosol optical tweezers, inferring the viscosity from the time scale for a composite particle to relax to a perfect sphere following the coalescence of two particles. Aerosol measurements compare well with bulk phase studies (well within an order of magnitude deviation at worst) over ranges of water activity accessible to both. Predictions of pure component viscosity from group contribution approaches combined with either nonideal or ideal mixing reproduce the RH-dependent trends particularly well for the alcohol, di-, and tricarboxylic acid systems extending up to viscosities of 104 Pa s. By contrast, predictions overestimate the viscosity by many orders of magnitude for the mono-, di-, and trisaccharide systems, components for which the pure component subcooled melt viscosities are ?1012 Pa s. When combined with a typical scheme for simulating the oxidation of alpha-pinene, a typical atmospheric pathway to secondary organic aerosol (SOA), these predictive tools suggest that the pure component viscosities are less than 106 Pa s for ~97% of the 50,000 chemical products included in the scheme. These component viscosities are consistent with the conclusion that the viscosity of alpha-pinene SOA is most likely in the range 105 to 108 Pa s. Potential improvements to the group contribution predictive tools for pure component viscosities are considered. PMID- 27684279 TI - Iridium-Catalyzed Asymmetric Addition of Thiophenols to Oxabenzonorbornadienes. AB - A highly efficient asymmetric ring addition reaction of oxabenzonorbornadienes with thiophenols using an iridium/(S)-xyl-binap catalyst is developed. This catalyst system overcomes catalyst poisoning and background reactions and allows the formation of exclusive thiol addition products in high yields (up to 97% yield) with excellent enantioselectivities (up to 98% ee). Particularly noteworthy is that no competitive ring-opened side products are observed. X-ray crystal structure analysis confirmed the adduct is solely in the exo configuration. PMID- 27684280 TI - Genetic Engineering of an Unconventional Yeast for Renewable Biofuel and Biochemical Production. AB - Yarrowia lipolytica is a non-pathogenic, dimorphic and strictly aerobic yeast species. Owing to its distinctive physiological features and metabolic characteristics, this unconventional yeast is not only a good model for the study of the fundamental nature of fungal differentiation but is also a promising microbial platform for biochemical production and various biotechnological applications, which require extensive genetic manipulations. However, genetic manipulations of Y. lipolytica have been limited due to the lack of an efficient and stable genetic transformation system as well as very high rates of non homologous recombination that can be mainly attributed to the KU70 gene. Here, we report an easy and rapid protocol for the efficient genetic transformation and for gene deletion in Y. lipolytica Po1g. First, a protocol for the efficient transformation of exogenous DNA into Y. lipolytica Po1g was established. Second, to achieve the enhanced double-crossover homologous recombination rate for further deletion of target genes, the KU70 gene was deleted by transforming a disruption cassette carrying 1 kb homology arms. Third, to demonstrate the enhanced gene deletion efficiency after deletion of the KU70 gene, we individually deleted 11 target genes encoding alcohol dehydrogenase and alcohol oxidase using the same procedures on the KU70 knockout platform strain. It was observed that the rate of precise homologous recombination increased substantially from less than 0.5% for deletion of the KU70 gene in Po1g to 33% 71% for the single gene deletion of the 11 target genes in Po1g KU70Delta. A replicative plasmid carrying the hygromycin B resistance marker and the Cre/LoxP system was constructed, and the selection marker gene in the yeast knockout strains was eventually removed by expression of Cre recombinase to facilitate multiple rounds of targeted genetic manipulations. The resulting single-gene deletion mutants have potential applications in biofuel and biochemical production. PMID- 27684282 TI - Omnidirectionally Stretchable and Transparent Graphene Electrodes. AB - Stretchable and transparent electrodes have been developed for applications in flexible and wearable electronics. For customer-oriented practical applications, the electrical and optical properties of stretchable electrodes should be independent of the directions of the applied stress, and such electrodes are called omnidirectionally stretchable electrodes. Herein, we report a simple and cost-effective approach for the fabrication of omnidirectionally stretchable and transparent graphene electrodes with mechanical durability and performance reliability. The use of a Fresnel lens-patterned electrode allows multilayered graphene sheets to achieve a concentric circular wavy structure, which is capable of sustaining tensile strains in all directions. The as-prepared electrodes exhibit high optical transparency, low sheet resistance, and reliable electrical performances under various deformation (e.g., bending, stretching, folding, and buckling) conditions. Furthermore, computer simulations have also been carried out to investigate the response of a Fresnel lens-patterned structure on the application of mechanical stresses. This study can be significant in a large variety of potential applications, ranging from stretchable devices to electronic components in various wearable integrated systems. PMID- 27684281 TI - Murine Flexor Tendon Injury and Repair Surgery. AB - Tendon connects skeletal muscle and bone, facilitating movement of nearly the entire body. In the hand, flexor tendons (FTs) enable flexion of the fingers and general hand function. Injuries to the FTs are common, and satisfactory healing is often impaired due to excess scar tissue and adhesions between the tendon and surrounding tissue. However, little is known about the molecular and cellular components of FT repair. To that end, a murine model of FT repair that recapitulates many aspects of healing in humans, including impaired range of motion and decreased mechanical properties, has been developed and previously described. Here an in-depth demonstration of this surgical procedure is provided, involving transection and subsequent repair of the flexor digitorum longus (FDL) tendon in the murine hind paw. This technique can be used to conduct lineage analysis of different cell types, assess the effects of gene gain or loss-of function, and to test the efficacy of pharmacological interventions in the healing process. However, there are two primary limitations to this model: i) the FDL tendon in the mid-portion of the murine hind paw, where the transection and repair occur, is not surrounded by a synovial sheath. Therefore this model does not account for the potential contribution of the sheath to the scar formation process. ii) To protect the integrity of the repair site, the FT is released at the myotendinous junction, decreasing the mechanical forces of the tendon, likely contributing to increased scar formation. Isolation of sufficient cells from the granulation tissue of the FT during the healing process for flow cytometric analysis has proved challenging; cytology centrifugation to concentrate these cells is an alternate method used, and allows for generation of cell preparations on which immunofluorescent labeling can be performed. With this method, quantification of cells or proteins of interest during FT healing becomes possible. PMID- 27684283 TI - Solvatochromic Probes Displaying Unprecedented Organic Liquids Discriminating Characteristics. AB - Four highly fluorescent derivatives of bis(phenyl-ethynyl-)-2-naphthyl (BPEN) with push-pull structures were designed and synthesized, of which azetidine was adopted as an electron-donating unit. For the electron withdrawing moiety, it varies from hydrogen, to formyl, then to the 2-ethoxyethyl derivative of dicyanovinyl, and finally to dicyanovinyl itself, and the corresponding fluorophores are denoted as A1, A2, A3, and A4, respectively. To enhance the solubility of the compounds, two n-hexadecyl residues were grafted onto the side positions of BPEN. Interestingly, introduction of azetidine not only improves the fluorescence quantum yield and enlarges the Stoke's shift of the parent compound but also endows them, in particular A2 and A4, exceptional capability to distinguish structurally relevant organic liquids, such as ethylbenzene and its isomers (o-xylenes, m-xylenes, and p-xylenes), monoalkyl-substituted benzene derivatives, gasolines of different grades, and other organic liquids. Theoretical calculation and Lippert-Mataga equation-based tests revealed the intramolecular charge transfer (ICT) nature of the solvatochromic properties of the compounds. Further quantitative analysis of the data obtained from studies of the probes/n-hexane-dioxane systems revealed the big differences in the dipole moments between the excited and ground states of A1, A2, A3, and A4, which are about 23, 29, 43, and 38 D, respectively. Moreover, the four novel fluorophores possess exceptional photochemical stability as demonstrated by the fact that more than 2 h of UV light illumination did not result in detectable reduction in the fluorescence emission of the fluorophores. It is the long wavelength absorption (>380, ~400, >410, and >430 nm), large molar absorption coefficient (>59 000, >52 000, >39 000, and >34 000 cm-1 M-1), great color change (400-620 nm), and good solubility in common organic liquids that makes the as developed compounds, in particular A2 and A4, very competitive solvatochromic probes. PMID- 27684285 TI - New Generation of Gold Nanoshell-Coated Esophageal Stent: Preparation and Biomedical Applications. AB - Esophageal cancer is one of the six most common cancers in the world, constituting ~7% of the gastrointestinal cancers. Esophageal stents can be inserted into the esophagus to open the pathway as a palliative treatment for advanced esophageal cancer. For the treatment of esophageal cancer, a series of anticancer drug-loaded stents such as paclitaxel or 5-fluorouracil/esophageal stent combinations have been prepared by covering a nitinol stent with a polymer or hydrogel shell. For the first time, we developed a gold nanoshell (AuNS) coated stent with high photothermal efficiency and used in the repetitive photothermal therapy of esophageal cancer. The functionalized stent was prepared by using surface-coated polydopamine as the Au3+ anchor and template. The thickness of the AuNS can be easily adjusted by controlling the reaction time and amount of Au3+. The AuNS-coated stent efficiently increased the temperature of pork and porcine intestines irradiated with a near-infrared (NIR) laser. The deep penetration of the NIR laser and excellent stability of the stent provide opportunity for the clinical applications of the newly functionalized stent. In vitro toxicity experiments showed excellent biocompatibility and safety of this device. Compared with bare metal stent, AuNS-modified stent exhibits great potential to open the duct passageway and suppress tumor growth in future clinical applications. PMID- 27684284 TI - Inflammasome-Derived Exosomes Activate NF-kappaB Signaling in Macrophages. AB - Exosomes are secreted small vesicles that mediate various biological processes, such as tumorigenesis and immune response. However, whether the inflammasome signaling leads to the change of constituent of exosomes and its roles in immune response remains to be determined. We isolated the exosomes from macrophages with treatment of mock, endotoxin, or endotoxin/nigericin. A label-free quantification method by MS/MS was used to identify the components of exosomes. In total, 2331 proteins were identified and 513 proteins were exclusively detected in exosomes with endotoxin and nigericin treatment. The differentially expressed proteins were classified by Gene Ontology and KEGG pathways. The immune response-related proteins and signaling pathways were specifically enriched in inflammasome derived exosomes. Moreover, we treated macrophages with the exosomes from different stimulation. We found that inflammasome-derived exosomes directly activate NF-kappaB signaling pathway, while the control or endotoxin-derived exosomes have no effect. The inflammatory signaling was amplified in neighbor cells in an exosome-dependent way. The inflammasome-derived exosomes might be used to augment the immune response in disease treatment, and preventing the transfer of these exosomes might ameliorate autoimmune diseases. PMID- 27684287 TI - Erratum for Euro Surveill. 2015;20(45). PMID- 27684286 TI - Preparation of Single-cohort Colonies and Hormone Treatment of Worker Honeybees to Analyze Physiology Associated with Role and/or Endocrine System. AB - Honeybee workers are engaged in various tasks related to maintaining colony activity. The tasks of the workers change according to their age (age-related division of labor). Young workers are engaged in nursing the brood (nurse bees), while older workers are engaged in foraging for nectar and pollen (foragers). The physiology of the workers changes in association with this role shift. For example, the main function of the hypopharyngeal glands (HPGs) changes from the secretion of major royal jelly proteins (MRJPs) to the secretion of carbohydrate metabolizing enzymes. Because worker tasks change as the workers age in typical colonies, it is difficult to discriminate the physiological changes that occur with aging from those that occur with the role shift. To study the physiological changes in worker tissues, including the HPGs, in association with the role shift, it would be useful to manipulate the honeybee colony population by preparing single-cohort colonies in which workers of almost the same age perform different tasks. Here we describe a detailed protocol for preparing single-cohort colonies for this analysis. Six to eight days after single-cohort colony preparation, precocious foragers that perform foraging tasks earlier than usual appear in the colony. Representative results indicated role-associated changes in HPG gene expression, suggesting role-associated HPG function. In addition to manipulating the colony population, analysis of the endocrine system is important for investigating role-associated physiology. Here, we also describe a detailed protocol for treating workers with 20-hydroxyecdysone (20E), an active form of ecdysone, and methoprene, a juvenile hormone analogue. The survival rate of treated bees was sufficient to examine gene expression in the HPGs. Gene expression changes were observed in response to 20E- and/or methoprene-treatment, suggesting that hormone treatments induce physiological changes of the HPGs. The protocol for hormone treatment described here is appropriate for examining hormonal effects on worker physiology. PMID- 27684288 TI - Nematicidal Stemona Alkaloids from Stemona parviflora. AB - Eight new alkaloids, 3beta-n-butylstemonamine (1), 8-oxo-3beta-n-butylstemonamine (2), 3-n-butylneostemonine (3), 10-epi-3-n-butylneostemonine (4), 8-oxo oxymaistemonine (5) protostemonine N4-oxide (6), (19S)-hydroxy-21 methoxystemofoline (7), and parvistemonine A (8), were isolated from the roots of Stemona parviflora, together with 17 known alkaloids. The structures of the new alkaloids were elucidated based on a comprehensive spectroscopic data analysis. The absolute configurations of 1-4 were determined by the ECD exciton chirality method and quantum ECD calculations. Protostemonine (10) and stemofoline (12) showed strong nematicidal activity against Panagrellus redivevus, with IC50 values of 0.10 and 0.46 MUM, respectively. PMID- 27684289 TI - Does the use of HIV testing and counseling services influence condom use among low-paid female sex workers in Guangxi, China? AB - HIV testing and counseling (HTC) are increasingly used in China during routine medical care visits to health facilities. However, limited data are available regarding the association between the utilization of HTC services and condom use among low-paid female sex workers (FSWs) who are at high risk of HIV infection but are hard to reach. A cross-sectional study was conducted among 794 low-paid FSWs in a city of Guangxi Zhuang Autonomous Region in 2011. Results showed that 71.7% of low-paid FSWs had utilized HTC services in the previous year and 65.7% reported having used a condom during the last sexual intercourse with their clients. Multivariate logistic regression analysis showed that utilizing HTC services was significantly and positively associated with the condom use. It also indicated that low-paid FSWs who were older, married, had higher education, earned less money, had high number of clients, had a history of sexually transmitted diseases, or had little or no HIV knowledge were less likely to use a condom during the last sexual encounter. The study suggests that HTC services need to be scaled up and made more accessible for this vulnerable population. PMID- 27684290 TI - Evaluation of the Relationship Between Pharmacokinetics and the Safety of Aripiprazole and Its Cardiovascular Effects in Healthy Volunteers. AB - AIMS: The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval. METHODS: The study population comprised 157 healthy volunteers from 6 bioequivalence clinical trials. Subjects were administered a single 10-mg oral dose of each formulation separated by a 28-day washout period. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. Blood pressure was measured at the following times: predose and 0.5, 2, 4, 6, and 8 hours postdose. An electrocardiogram was recorded at predose, 4, and 8 hours postdose. RESULTS: Area under the curve (AUC), maximum plasma concentration, half-life, and distribution volume corrected for weight were higher in women. Aripiprazole treatment produced a decrease of BP (9.3 mm Hg on systolic and 6.2 mm Hg on diastolic pressure) and an increase in HR (12.1 beats per minute) and QTc interval (9.1 milliseconds). There were sex differences in BP, HR, and QTc interval. Women and subjects with higher AUC and maximum plasma concentration values were more prone to experience adverse drug reactions and gastrointestinal adverse reactions. The AUC was related with systolic BP and diastolic BP decrease and HR increase but there was no relationship between aripiprazole concentrations and QTc increase. CONCLUSIONS: Aripiprazole decreases BP and increases HR and QTc interval. Pharmacokinetics, pharmacodynamics, and safety of aripiprazole are affected by sex. There is a directly proportional relationship between pharmacokinetic parameters and adverse drug reactions and effect on BP and HR. PMID- 27684292 TI - Statistics Commentary Series: Commentary No. 17-Validity. PMID- 27684291 TI - Selective Serotonin Reuptake Inhibitors and Operative Bleeding Risk: A Review of the Literature. AB - OBJECTIVE: This study aimed to review the data on the effect of selective serotonin reuptake inhibitors (SSRIs) on bleeding during or after operative procedures and to offer guidelines for clinical management. DATA SOURCES: Search of PubMed and MEDLINE for all articles in English from 1990-2016 with key words depression, antidepressants, bleeding, platelets, and operation. STUDY SELECTION: Studies were included if they reported information on bleeding complications during operative or childbirth procedures in patients taking antidepressants. DATA EXTRACTION: Because of the limited number and heterogeneity of studies with respect to the range of operative procedures and definition of bleeding complications, a qualitative approach was taken to summarize results rather than abstracting and aggregating data. RESULTS: The weight of the evidence is that SSRI use increases the risk of bleeding complications during and immediately after surgery. However, given the limited data, we cannot estimate the risk for a given patient having a given procedure. CONCLUSIONS: Clinicians must consider the risk-to-benefit ratio of discontinuing an SSRI before an elective operative procedure. Discontinuing SSRI medications may result in discontinuation syndrome, symptom recrudescence, or relapse of depression, whereas continuing an SSRI during surgery exposes patients to significant bleeding risks. Antidepressant prescribers must be cognizant of and take responsibility for discussing this potential problem and considering different options. This issue must also be the responsibility of the doctor performing the procedure, but, frequently, it will be the prescribing physician who alerts the surgeon to the potential bleeding risk associated with SSRIs. PMID- 27684293 TI - Cataract surgery and age-related macular degeneration. AB - PURPOSE OF REVIEW: The following review describes the recent evidence regarding the effect of cataract surgery on age-related macular degeneration (AMD). RECENT FINDINGS: For patients with both visually significant cataracts and AMD, recent evidence supports the role of cataract surgery with reports demonstrating improved visual acuity, absence of significant disease progression, and improved quality of life. SUMMARY: Recent evidence does not find cataract surgery to cause or worsen AMD. PMID- 27684294 TI - Immediately sequential bilateral cataract surgery: advantages and disadvantages. AB - PURPOSE OF REVIEW: The number of cataract surgeries performed globally will continue to rise to meet the needs of an aging population. This increased demand will require healthcare systems and providers to find new surgical efficiencies while maintaining excellent surgical outcomes. Immediately sequential bilateral cataract surgery (ISBCS) has been proposed as a solution and is increasingly being performed worldwide. The purpose of this review is to discuss the advantages and disadvantages of ISBCS. RECENT FINDINGS: When appropriate patient selection occurs and guidelines are followed, ISBCS is comparable with delayed sequential bilateral cataract surgery in long-term patient satisfaction, visual acuity and complication rates. In addition, the risk of bilateral postoperative endophthalmitis and concerns of poorer refractive outcomes have not been supported by the literature. ISBCS is cost-effective for the patient, healthcare payors and society, but current reimbursement models in many countries create significant financial barriers for facilities and surgeons. SUMMARY: As demand for cataract surgery rises worldwide, ISBCS will become increasingly important as an alternative to delayed sequential bilateral cataract surgery. Advantages include potentially decreased wait times for surgery, patient convenience and cost savings for healthcare payors. Although they are comparable in visual acuity and complication rates, hurdles that prevent wide adoption include liability concerns as ISBCS is not an established standard of care, economic constraints for facilities and surgeons and inability to fine-tune intraocular lens selection in the second eye. Given these considerations, an open discussion regarding the advantages and disadvantages of ISBCS is important for appropriate patient selection. PMID- 27684295 TI - An Easy Method for Plant Polysome Profiling. AB - Translation of mRNA to protein is a fundamental and highly regulated biological process. Polysome profiling is considered as a gold standard for the analysis of translational regulation. The method described here is an easy and economical way for fractionating polysomes from various plant tissues. A sucrose gradient is made without the need for a gradient maker by sequentially freezing each layer. Cytosolic extracts are then prepared in a buffer containing cycloheximide and chloramphenicol to immobilize the cytosolic and chloroplastic ribosomes to mRNA and are loaded onto the sucrose gradient. After centrifugation, six fractions are directly collected from the bottom to the top of the gradient, without piercing the ultracentrifugation tube. During collection, the absorbance at 260 nm is read continuously to generate a polysome profile that gives a snapshot of global translational activity. Fractions are then pooled to prepare three different mRNA populations: the polysomes, mRNAs bound to several ribosomes; the monosomes, mRNAs bound to one ribosome; and mRNAs that are not bound to ribosomes. mRNAs are then extracted. This protocol has been validated for different plants and tissues including Arabidopsis thaliana seedlings and adult plants, Nicotiana benthamiana, Solanum lycopersicum, and Oryza sativa leaves. PMID- 27684296 TI - Determination of Colistin and Colistimethate Levels in Human Plasma and Urine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry. AB - BACKGROUND: Colistin is a polypeptide antibiotic from the polymyxin E group used for the treatment of infections caused by multidrug-resistant gram-negative bacteria. The main constituents, accounting for approximately 85% of this mixture, are colistin A (polymyxin E1) and colistin B (polymyxin E2). The aim of this study was to develop and validate new and fast methods of quantification of colistin A and B and its precursors [colistin methanesulfonate sodium (CMS) A and B] by ultraperformance liquid chromatography-tandem mass spectrometry in plasma and urine with short pretreatment and run times. METHODS: Chromatography was performed on an Acquity UPLC-MS/MS system (WATERS) with a WATERS Acquity UPLC C18 column (4.6 * 150 mm, 3.5 MUm particle size). The pretreatment of samples consists of precipitation and extraction into microcolumns plate and HLB 96-well plate 30 MUm-30 mg (OASIS) with a Positive Pressure-96 (WATERS). RESULTS: Quantification was performed using a multiple reaction monitoring of the following transitions: m/z 390.9 -> 385.1 for colistin A, m/z 386.2 -> 101.0 for colistin B, and m/z 602.4 -> 241.1 for polymyxin B1 sulfate. In plasma and urine, calibration curves were linear from 30 to 6000 ng/mL for colistin A and from 15 to 3000 ng/mL for colistin B. With an acceptable accuracy and precision, the lower limit of quantification were set at 24.0 ng/mL and 12.0 ng/mL for colistin A and B in plasma, and at 18.0 ng/mL and 9.0 ng/mL for colistin A and B in urine. CONCLUSIONS: These LC-MS/MS methods of quantification for colistin A and B and its precursors (CMS A and B) in plasma and urine are fast, simple, specific, sensitive, accurate, precise, and reliable. Furthermore, they are linear and repeatable. These procedures were successfully applied to a pharmacokinetic study of a critically ill patient suffering from ventilator-associated pneumonia, who was treated with nebulized CMS. PMID- 27684297 TI - Extent of Resection and Survival in Glioblastoma Multiforme. PMID- 27684299 TI - A Young Man With Hypercalcemia. PMID- 27684298 TI - Upregulation of miR-9 and Let-7a by nanoencapsulated chrysin in gastric cancer cells. AB - Chrysin, as a flavone, has showed cancer chemopreventive activity. The present study utilized the PLGA-PEG-chrysin to evaluate the expression of miR-9 and Let 7a in human gastric cells. The structure of nanoparticles and encapsulated chrysin was evaluated using 1H NMR, FT-IR, and SEM. MTT assay was used for the evaluation of cytotoxicity effect of nanoencapsulated chrysin. Expression levels of miR-9 and Let7-a were studied by real-time PCR. The results demonstrated that chrysin-PLGA-PEG nanoparticles are more effective than pure chrysin in upregulation of miR-9 and Let-7a due to enhanced uptake by cells. Therefore, PLGA PEG could be a superior carrier for this kind of hydrophobic agent. PMID- 27684300 TI - Are 12-lead ECG findings associated with the risk of cardiovascular events after ischemic stroke in young adults? AB - INTRODUCTION: Ischemic stroke (IS) in a young patient is a disaster and recurrent cardiovascular events could add further impairment. Identifying patients with high risk of such events is therefore important. The prognostic relevance of ECG for this population is unknown. MATERIALS AND METHODS: A total of 690 IS patients aged 15-49 years were included. A 12-lead ECG was obtained 1-14 d after the onset of stroke. We adjusted for demographic factors, comorbidities, and stroke characteristics, Cox regression models were used to identify independent ECG parameters associated with long-term risks of (1) any cardiovascular event, (2) cardiac events, and (3) recurrent stroke. RESULTS: Median follow-up time was 8.8 years. About 26.4% of patients experienced a cardiovascular event, 14.5% had cardiac events, and 14.6% recurrent strokes. ECG parameters associated with recurrent cardiovascular events were bundle branch blocks, P-terminal force, left ventricular hypertrophy, and a broader QRS complex. Furthermore, more leftward P wave axis, prolonged QTc, and P-wave duration >120 ms were associated with increased risks of cardiac events. No ECG parameters were independently associated with recurrent stroke. CONCLUSION: A 12-lead ECG can be used for risk prediction of cardiovascular events but not for recurrent stroke in young IS patients. KEY MESSAGES ECG is an easy, inexpensive, and useful tool for identifying young ischemic stroke patients with a high risk for recurrent cardiovascular events and it has a statistically significant association with these events even after adjusting for confounding factors. Bundle branch blocks, P-terminal force, broader QRS complex, LVH according to Cornell voltage duration criteria, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms are predictors for future cardiovascular or cardiac events in these patients. No ECG parameters were independently associated with recurrent stroke. PMID- 27684301 TI - Reliability of a Seven-Segment Foot Model with Medial and Lateral Midfoot and Forefoot Segments During Walking Gait. AB - In-vitro and invasive in-vivo studies have reported relatively independent motion in the medial and lateral forefoot segments during gait. However, most current surface-based models have not defined medial and lateral forefoot or midfoot segments. The purpose of the current study was to determine the reliability of a 7-segment foot model that includes medial and lateral midfoot and forefoot segments during walking gait. Three-dimensional positions of marker clusters located on the leg and 6 foot segments were tracked as 10 participants completed 5 walking trials. To examine the reliability of the foot model, coefficients of multiple correlation (CMC) were calculated across the trials for each participant. Three-dimensional stance time series and range of motion (ROM) during stance were also calculated for each functional articulation. CMCs for all of the functional articulations were >= 0.80. Overall, the rearfoot complex (leg calcaneus segments) was the most reliable articulation and the medial midfoot complex (calcaneus-navicular segments) was the least reliable. With respect to ROM, reliability was greatest for plantarflexion/dorsiflexion and least for abduction/adduction. Further, the stance ROM and time-series patterns results between the current study and previous invasive in-vivo studies that have assessed actual bone motion were generally consistent. PMID- 27684302 TI - Effect of Bronsted acids on the thiophenol-mediated radical addition translocation-cyclization process for the preparation of pyrrolidine derivatives. AB - A thiophenol-mediated method for the conversion of propargylamines to pyrrolidines under acidic conditions is described. This cascade reaction involves addition of a thiyl radical to the terminal alkyne followed by a 1,5-hydrogen transfer (radical translocation) and a rapid cyclization affording the pyrrolidine ring. Our studies reveal that complete protonation of the tertiary amine with 10 equivalents of trifluoroacetic acid avoids undesired hydrogen atom abstractions by the thiyl radicals. PMID- 27684303 TI - Subjective meanings of 'unintended' pregnancy: interviews from understanding fertility management in contemporary Australia. AB - Unintended pregnancy can be difficult to identify and conceptualise. We aimed to understand how unintended pregnancies are constructed, explained and situated in a reproductive life. A total of 41 women and 7 men aged 20-50 years were interviewed in depth. Transcripts were analysed using iterative hermeneutic techniques informed by narrative theory. Of 34 participants who had been pregnant or had a partner in pregnancy, 12 women and 1 man described 23 'unintended' pregnancies, about half of which ended in abortion. Their accounts reveal that an unintended pregnancy is identified subjectively, that the same pregnancy may be identified by one partner in the pregnancy as unintended and by the other as intended, and that a researcher's supposedly objective assessment of an unintended pregnancy may be inconsistent with the assessment of the woman who experienced it. A pejorative discourse was evident, predominantly among participants who did not report having an unintended pregnancy: women use an 'unintended' pregnancy to entrap men. Accounts from five participants reporting an unintended pregnancy were selected for illustration. An appreciation of the role such a pregnancy might play in an individual life requires a nuanced understanding of the complexity of human experience and a resistance to simple binary categorisation. PMID- 27684304 TI - Deliberate and spontaneous sensations of disembodiment: capacity or flaw? AB - INTRODUCTION: Hallucinations that involve shifts in the subjectively experienced location of the self, have been termed "out-of-body experiences" (OBEs). Early psychiatric accounts cast OBEs as a specific instance of depersonalisation and derealisation disorder (DPD-DR). However, during feelings of alienation and lack of body realism in DPD-DR the self is experienced within the physical body. Deliberate forms of "disembodiment" enable humans to imagine another's visuo spatial perspective taking (VPT), thus, if a strong relationship between deliberate and spontaneous forms of disembodiment could be revealed, then uncontrolled OBEs could be "the other side of the coin" of a uniquely human capacity. METHODS: We present a narrative review of behavioural and neuroimaging work emphasising methodological and theoretical aspects of OBE and VPT research and a potential relationship. RESULTS: Results regarding a direct behavioural relationship between VPT and OBE are mixed and we discuss reasons by pointing out the importance of using realistic tasks and recruiting genuine OBEers instead of general DPD-DR patients. Furthermore, we review neuroimaging evidence showing overlapping neural substrates between VPT and OBE, providing a strong argument for a relationship between the two processes. CONCLUSIONS: We conclude that OBE should be regarded as a necessary implication of VPT ability in humans, or even as a necessary and potentially sufficient condition for the evolution of VPT. PMID- 27684306 TI - Understanding Texts with the Help of Experimentation: The Example of Cupellation in Arabic Scientific Literature. AB - The article aims to show how experimentation can help us understand historical texts, by focusing on the specific case of cupellation in Arabic scientific literature. It also provides new information about cupellation in the Arab-Muslim Middle Ages. The article consists of translations of three of the most detailed accounts of cupellation: Hamdani's Kitab al-jawharatayn al-'atiqatayn (first half of the fourth/tenth century), Maslama b. Qasim al-Qurtubi, Rutbat al-hakim (339 342/950-953), and Mansur b. Ba'ra, Kitab kashf al-asrar al-'ilmiyya bi-dar al darb al-misriyya (615-635/1218-1238). These are accompanied by commentaries based on a series of experiments carried out in the course of archaeological research on cupellation, which are here used to shed new light on the medieval texts and resolve several problems in interpreting them. PMID- 27684305 TI - The epidemiology of PTSD and depression in refugee minors who have resettled in developed countries. AB - BACKGROUND: With an increasing number of refugees migrating across continents, the crisis is very apparent. AIM: A literature review of patterns, risk factors and effects of post-traumatic stress disorder (PTSD) and depression in refugee minors was carried out involving those who have resettled in different developed countries. METHODS: Papers were narrowed down by reading the abstracts and methods to ascertain whether the refugee children had resettled in developed countries and to ensure that they had not just been internally displaced. RESULTS: High incidences of PTSD and depression were found in refugee minors and poorer mental health was correlated with increased exposure to violence. Factors such as social support and family security were important in reducing the rates of PTSD and depression, whereas the implications of age and gender were unclear. Long-term effects from these mental illnesses indicated scholastic issues, but no further worsening of symptoms. CONCLUSIONS: Further research is needed regarding the follow-up of refugee minors with PTSD and depression to allow the establishment of more effective support systems, as long-term outcomes become more clearly understood. Few papers discuss the influence of religion, which may be an interesting line of future research as refugees move to more secular societies. PMID- 27684307 TI - Clinical neuropsychology practice and training in Canada. AB - OBJECTIVE: This invited paper provides information about professional neuropsychology issues in Canada and is part of a special issue addressing international perspectives on education, training, and practice in clinical neuropsychology. METHOD: Information was gathered from literature searches and personal communication with other neuropsychologists in Canada. RESULTS: Canada has a rich neuropsychological history. Neuropsychologists typically have doctoral level education including relevant coursework and supervised practical experience. Licensure requirements vary across the 10 provinces and there are regional differences in salary. While training at the graduate and internship level mirrors that of our American colleagues, completion of a two-year postdoctoral fellowship in neuropsychology is not required to obtain employment in many settings and there are few postdoctoral training programs in this country. The majority of neuropsychologists are employed in institutional settings (e.g. hospitals, universities, rehabilitation facilities), with a growing number entering private practice or other settings. There are challenges in providing neuropsychological services to the diverse Canadian population and a need for assessment measures and normative data in multiple languages. CONCLUSIONS: Canadian neuropsychologists face important challenges in defining ourselves as distinct from other professions and other psychologists, in maintaining funding for high-quality training and research, in establishing neuropsychology-specific training and practice standards at the provincial or national level, and ensuring the clinical care that we provide is efficient and effective in meeting the needs of our patient populations and consumers, both within and outside of the publically funded health care system. PMID- 27684311 TI - CORRIGENDUM: The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. PMID- 27684308 TI - Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia. AB - OBJECTIVES: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. METHODS: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. RESULTS: HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% +/- 0.12% with linagliptin/metformin (n = 132) and -2.02% +/- 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c >=9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to 0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference 0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. CONCLUSION: Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT01512979. PMID- 27684312 TI - The architecture of prions: how understanding would provide new therapeutic insights. AB - Compelling evidence from the last three decades clearly shows that transmissible spongiform encephalopathies (TSEs) develop as a result of a poorly understood misfolding event that converts the cellular prion protein (PrPC) to an isoform known as PrPSc which is aggregated, protease resistant and able to impose its aberrant conformation onto PrPC, leading to its accumulation in the central nervous system. Despite all the knowledge gathered in more than thirty years of research and the general understanding of the pathological processes, the molecular mechanisms remain elusive, making it difficult to develop rational therapeutic strategies for this group of incurable diseases. In this review article, we give an overview of what is known about prion architecture and how the limited structural information available has been used in the quest for remedies for these devastating disorders. PMID- 27684314 TI - Co-composting of two-phase olive-mill pomace and poultry manure with tomato harvest stalks. AB - In this study, two-phase olive-mill pomace with poultry manure and chopped tomato harvest stalks were composted at different initial carbon/nitrogen (C/N) ratios with fixed free air space of 35%. Composting experiment was carried out in the 15 aerobic reactors made of stainless steel and was monitored for 28 days. During the composting process, temperature, moisture content, organic matter (OM), pH, electrical conductivity, oxygen and carbon dioxide concentrations, total carbon, total nitrogen, ammonium nitrogen ([Formula: see text]), nitrate nitrogen ([Formula: see text]), and total phosphorus were monitored. Compost mass and volume changes were determined at the beginning, during remixings, and at the end of composting. While the stabilization period took less time for the mixtures containing a high amount of poultry manure, the mixtures having the high portion of two-phase olive-mill pomace took a longer time due to the structure of olive stone and its lignin content. Dry matter loss (range: 18.1-34.0%.) in the mixtures increased with an increase in the share of poultry manure and tomato stalks in the initial mixture. OM loss (range: 21.7-46.1%) for tomato stalks (measured separately) during composting increased due to an increase in the ratio of poultry manure in the initial mixtures. PMID- 27684315 TI - Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter. AB - The plant circadian clock allows the anticipation of daily changes to the environment. This anticipation aids the responses to temporally predictable biotic and abiotic stress. Conversely, disruption of circadian timekeeping severely compromises plant health and reduces agricultural crop yields. It is therefore imperative that we understand the intricate regulation of circadian rhythms in plants, including the factors that affect motion of the transcriptional clockwork itself. Testing circadian defects in the model plant Arabidopsis thaliana (Arabidopsis) traditionally involves crossing specific mutant lines to a line rhythmically expressing firefly luciferase from a circadian clock gene promoter. This approach is laborious, time-consuming, and could be fruitless if a mutant has no circadian phenotype. The methodology presented here allows a rapid initial assessment of circadian phenotypes. Protoplasts derived from mutant and wild-type Arabidopsis are isolated, transfected with a rhythmically expressed luminescent reporter, and imaged under constant light conditions for 5 days. Luminescent traces will directly reveal whether the free-running period of mutant plants is different from wild-type plants. The advantage of the method is that any Arabidopsis line can efficiently be screened, without the need for generating a stably transgenic luminescent clock marker line in that mutant background. PMID- 27684316 TI - Wearable In-Ear Encephalography Sensor for Monitoring Sleep. Preliminary Observations from Nap Studies. AB - RATIONALE: To date, EEG is the only quantifiable measure of the neural changes that define sleep. Although it is used widely for clinical testing, scalp electrode EEG is costly and is poorly tolerated by sleeping patients. OBJECTIVES: This was a pilot study to assess the agreement between EEG recordings obtained from a new ear-EEG sensor and those obtained simultaneously from standard scalp electrodes. METHODS: Participants were four healthy men, 25 to 36 years of age. During naps, EEG tracings were recorded simultaneously from the ear sensor and from standard scalp electrodes. A clinical expert, blinded to the data collection, analyzed 30-second epochs of recordings from both devices, using standardized criteria. The agreement between scalp- and ear-recordings was assessed. MEASUREMENTS AND MAIN RESULTS: We scored 360 epochs (scalp-EEG and ear EEG), of which 254 (70.6%) were scored as non-REM sleep using scalp-EEG. The ear EEG sensor had a sensitivity of 0.88 (95% confidence interval [CI], 0.82-0.92) and a specificity of 0.78 (95% CI, 0.70-0.84) in detecting N2/N3 sleep. The kappa coefficient between the scalp- and the ear-EEG was 0.65 (95% CI, 0.58-0.73). As a sleep monitor (all non-REM sleep stages vs. wake), the in-ear sensor had a sensitivity of 0.91 (95% CI, 0.87-0.94) and a specificity of 0.66 (95% CI, 0.56 0.75). The kappa coefficient was 0.60 (95% CI, 0.50-0.69). CONCLUSIONS: Substantial agreement was observed between recordings derived from a new ear-EEG sensor and conventional scalp electrodes on four healthy volunteers during daytime naps. PMID- 27684318 TI - Kinetics and Mechanism of Bioactivation via S-Oxygenation of Anti-Tubercular Agent Ethionamide by Peracetic Acid. AB - The kinetics and mechanism of the oxidation of the important antitubercular agent, ethionamide, ETA (2-ethylthioisonicotinamide), by peracetic acid (PAA) have been studied. It is effectively a biphasic reaction with an initial rapid first phase of the reaction which is over in about 5 s and a second slower phase of the reaction which can run up to an hour. The first phase involves the addition of a single oxygen atom to ethionamide to form the S-oxide. The second phase involves further oxidation of the S-oxide to desulfurization of ETA to give 2-ethylisonicotinamide. In contrast to the stability of most organosulfur compounds, the S-oxide of ETA is relatively stable and can be isolated. In conditions of excess ETA, the stoichiometry of the reaction was strictly 1:1: CH3CO3H + Et(C5H4)C(?S)NH2 -> CH3CO2H + Et(C5H4)C(?NH)SOH. In this oxidation, it was apparent that only the sulfur center was the reactive site. Though ETA was ultimately desulfurized, only the S-oxide was stable. Electrospray ionization (ESI) spectral analysis did not detect any substantial formation of the sulfinic and sulfonic acids. This suggests that cleavage of the carbon-sulfur bond occurs at the sulfenic acid stage, resulting in the formation of an unstable sulfur species that can react further to form more stable sulfur species. In this oxidation, no sulfate formation was observed. ESI spectral analysis data showed a final sulfur species in the form of a dimeric sulfur monoxide species, H3S2O2. We derived a bimolecular rate constant for the formation of the S-oxide of (3.08 +/- 0.72) * 102 M-1 s-1. Oxidation of the S-oxide further to give 2 ethylisonicotinamide gave zero order kinetics. PMID- 27684317 TI - Measurement of Vibration Detection Threshold and Tactile Spatial Acuity in Human Subjects. AB - Tests that allow the precise determination of psychophysical thresholds for vibration and grating orientation provide valuable information about mechanosensory function that are relevant for clinical diagnosis as well as for basic research. Here, we describe two psychophysical tests designed to determine the vibration detection threshold (automated system) and tactile spatial acuity (handheld device). Both procedures implement a two-interval forced-choice and a transformed-rule up and down experimental paradigm. These tests have been used to obtain mechanosensory profiles for individuals from distinct human cohorts such as twins or people with sensorineural deafness. PMID- 27684319 TI - Cooperative Palladium/Proline-Catalyzed Direct alpha-Allylic Alkylation of Ketones with Alkynes. AB - The cooperative palladium/l-proline-catalyzed direct alpha-allylic alkylation of ketones with alkynes is achieved. This reaction exhibits high atom economy since a leaving group is not liberated and a stoichiometric amount of extra oxidant is not needed. A broad range of functional groups are tolerated, and the reaction scope could be further expanded to aldehydes. PMID- 27684320 TI - Outcomes for family carers of a nurse-delivered hospital discharge intervention for older people (the Further Enabling Care at Home Program): Single blind randomised controlled trial. AB - BACKGROUND: Hospital discharge of older people receiving care at home offers a salient opportunity to identify and address their family caregivers' self identified support needs. OBJECTIVES: This study tested the hypothesis that the extent to which family caregivers of older people discharged home from hospital felt prepared to provide care at home would be positively influenced by their inclusion in the new Further Enabling Care at Home program. DESIGN: This single blind randomised controlled trial compared outcomes from usual care alone with those from usual care plus the new program. The program, delivered by a specially trained nurse over the telephone, included: support to facilitate understanding of the patient's discharge letter; caregiver support needs assessment; caregiver prioritisation of urgent needs; and collaborative guidance, from the nurse, regarding accessing supports. SETTING AND PARTICIPANTS: Dyads were recruited from the medical assessment unit of a Western Australian metropolitan public hospital. Each dyad comprised a patient aged 70 years or older plus an English speaking family caregiver. METHODS: The primary outcome was the caregiver's self-reported preparedness to provide care for the patient. Data collection time points were designated as: Time 1, within four days of discharge; Time 2, 15-21days after discharge; Time 3, six weeks after discharge. Other measures included caregivers' ratings of: their health, patients' symptoms and independence, caregiver strain, family well-being, caregiver stress, and positive appraisals of caregiving. Data were collected by telephone. RESULTS: Complete data sets were obtained from 62 intervention group caregivers and 79 controls. Groups were equivalent at baseline. Needs prioritised most often by caregivers were: to know whom to contact and what to expect in the future and to access practical help at home. Support guidance included how to: access help, information, and resources; develop crisis plans; obtain referrals and services; and organise legal requirements. Compared to controls, preparedness to care improved in the intervention group from Time 1 to Time 2 (effect size=0.52; p=0.006) and from Time 1 to Time 3 (effect size=0.43; p=0.019). These improvements corresponded to a change of approximately 2 points on the Preparedness for Caregiving instrument. Small but significant positive impacts were also observed in other outcomes, including caregiver strain. CONCLUSIONS: These unequivocal findings provide a basis for considering the Furthering Enabling Care at Home program's implementation in this and other similar settings. Further testing is required to determine the generalisability of results. PMID- 27684321 TI - Speaking up behaviours (safety voices) of healthcare workers: A metasynthesis of qualitative research studies. AB - BACKGROUND: A critical characteristic of effective teams in any setting is when each member is willing to speak up to share thoughts and ideas to improve processes. In spite of attempts by healthcare systems to encourage employees to speak up, employee silence remains a common cause of communication breakdowns, contributing to errors and suboptimal care delivery. Nurses in particular have reported low confidence in their communication abilities, and cite the belief that speaking up will not make a difference. OBJECTIVE: To develop an understanding of how nurses and other healthcare workers relate to safety voice behaviors and how this might influence clinical practice. DATA SOURCES: A search of the PubMed, CINAHL, and Academic Search Premier databases was conducted using keywords employee, nurse, qualitative, speak up, silence, safety, voice, and safety voice identified 372 articles with 11 retained after a review of the abstracts. Studies took place in Australia, Bulgaria, Canada, Hong Kong, East Africa, Ireland, Korea, New Zealand, Sweden, Switzerland, and the United States representing 504 healthcare workers including 354 nurses. METHODS: This interpretive meta-synthesis of 11 qualitative articles published from 2005 to 2015 was conducted using a social constructivist approach with thematic analysis. RESULTS: The four themes identified are: 1) hierarchies and power dynamics negatively affect safety voice, 2) open communication is unsafe and ineffective, 3) embedded expectations of nurse behavior affect safety voice, and 4) nurse managers have a powerful positive or negative affect on safety voice. CONCLUSIONS: Healthcare workers worldwide report multiple social and hierarchy related fears surrounding the utilization of safety voice behaviors. Hesitance to speak up is pervasive among nurses, as is low self-efficacy related to safety voice. The presence of caring leaders, peer support, and an organizational commitment to safe, open cultures, may improve safety voice utilization among nurses and other healthcare workers. PMID- 27684322 TI - Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells. AB - Eukaryotic cells sense and move towards a chemoattractant gradient, a cellular process referred as chemotaxis. Chemotaxis plays critical roles in many physiological processes, such as embryogenesis, neuron patterning, metastasis of cancer cells, recruitment of neutrophils to sites of inflammation, and the development of the model organism Dictyostelium discoideum. Eukaryotic cells sense chemo-attractants using G protein-coupled receptors. Visual chemotaxis assays are essential for a better understanding of how eukaryotic cells control chemoattractant-mediated directional cell migration. Here, we describe detailed methods for: 1) real-time, high-resolution monitoring of multiple chemotaxis assays, and 2) simultaneously visualizing the chemoattractant gradient and the spatiotemporal dynamics of signaling events in neutrophil-like HL60 cells. PMID- 27684323 TI - Lung motion estimation by robust point matching and spatiotemporal tracking for 4D CT. AB - We propose a deformable registration approach to estimate patient-specific lung motion during free breathing for four-dimensional (4D) computed tomography (CT) based on point matching and tracking between images in different phases. First, a robust point matching (RPM) algorithm coarsely aligns the source phase image onto all other target phase images of 4D CT. Scale-invariant feature transform (SIFT) is introduced into the cost function in order to accelerate and stabilize the convergence of the point matching. Next, the temporal consistency of the estimated lung motion model is preserved by fitting the trajectories of the points in the respiratory phase using L1 norm regularization. Then, the fitted positions of a point along the trajectory are used as the initial positions for the point tracking. Spatial mean-shift iteration is employed to track points in all phase images. The tracked positions in all phases are used to perform RPM again. These steps are repeated until the number of updated points is smaller than a given threshold sigma. With this method, the correspondence between the source phase image and other target phase image is established more accurately. Trajectory fitting ensures the estimated trajectory does not fluctuate violently. We evaluated our method by using the public DIR-lab, POPI-model, CREATIS and COPDgene lung datasets. In the experimental results, the proposed method achieved satisfied accuracy for image registration. Our method also preserved the topology of the deformation fields well for image registration with large deformation. PMID- 27684324 TI - Computer-Aided Detection (CADx) for Plastic Deformation Fractures in Pediatric Forearm. AB - Bowing fractures are incomplete fractures of tubular long bones, often observed in pediatric patients, where plain radiographic film is the non-invasive imaging modality of choice in routine radiological workflow. Due to weak association between bent bone and distinct cortex disruption, bowing fractures may not be diagnosed properly while reading plain radiography. Missed fractures and dislocations are common in accidents and emergency practice, particularly in children. These missed injuries can result in more complicated treatment or even long-term disability. The most common reason for missed fractures is that junior radiologists or physicians lack expertise in pediatric skeletal injury diagnosis. Not only is additional radiation exposure inevitable in the case of misdiagnosis, but other consequences include the patient's prolonged uncomfortableness and possible unnecessary surgical procedures. Therefore, a computerized image analysis system, which would be secondary to the radiologists' interpretations, may reduce adverse effects and improve the diagnostic rates of bowing fracture (detection and quantification). This system would be highly desirable and particularly useful in emergency rooms. To address this need, we investigated and developed a new Computer Aided Detection (CADx) system for pediatric bowing fractures. The proposed system has been tested on 226 cases of pediatric forearms with bowing fractures with respect to normal controls. Receiver operation characteristic (ROC) curves show that the sensitivity and selectivity of the developed CADx system are satisfactory and promising. A clinically feasible graphical user interface (GUI) was developed to serve the practical needs in the emergency room as a diagnostic reference. The developed CADx system also has strong potential to train radiology residents for diagnosing pediatric forearm bowing fractures. PMID- 27684325 TI - Laboratory Production of Biofuels and Biochemicals from a Rapeseed Oil through Catalytic Cracking Conversion. AB - The work is based on a reported study which investigates the processability of canola oil (bio-feed) in the presence of bitumen-derived heavy gas oil (HGO) for production of transportation fuels through a fluid catalytic cracking (FCC) route. Cracking experiments are performed with a fully automated reaction unit at a fixed weight hourly space velocity (WHSV) of 8 hr(-1), 490-530 degrees C, and catalyst/oil ratios of 4-12 g/g. When a feed is in contact with catalyst in the fluid-bed reactor, cracking takes place generating gaseous, liquid, and solid products. The vapor produced is condensed and collected in a liquid receiver at 15 degrees C. The non-condensable effluent is first directed to a vessel and is sent, after homogenization, to an on-line gas chromatograph (GC) for refinery gas analysis. The coke deposited on the catalyst is determined in situ by burning the spent catalyst in air at high temperatures. Levels of CO2 are measured quantitatively via an infrared (IR) cell, and are converted to coke yield. Liquid samples in the receivers are analyzed by GC for simulated distillation to determine the amounts in different boiling ranges, i.e., IBP-221 degrees C (gasoline), 221-343 degrees C (light cycle oil), and 343 degrees C+ (heavy cycle oil). Cracking of a feed containing canola oil generates water, which appears at the bottom of a liquid receiver and on its inner wall. Recovery of water on the wall is achieved through washing with methanol followed by Karl Fischer titration for water content. Basic results reported include conversion (the portion of the feed converted to gas and liquid product with a boiling point below 221 degrees C, coke, and water, if present) and yields of dry gas (H2 C2's, CO, and CO2), liquefied petroleum gas (C3-C4), gasoline, light cycle oil, heavy cycle oil, coke, and water, if present. PMID- 27684326 TI - Interconnected Nanoflake Network Derived from a Natural Resource for High Performance Lithium-Ion Batteries. AB - Numerous natural resources have a highly interconnected network with developed porous structure, so enabling directional and fast matrix transport. Such structures are appealing for the design of efficient anode materials for lithium ion batteries, although they can be challenging to prepare. Inspired by nature, a novel synthesis route from biomass is proposed by using readily available auricularia as retractable support and carbon coating precursor to soak up metal salt solution. Using the swelling properties of the auricularia with the complexation of metal ions, a nitrogen-containing MnO@C nanoflake network has been easily synthesized with fast electrochemical reaction dynamics and a superior lithium storage performance. A subsequent carbonization results in the in situ synthesis of MnO nanoparticles throughout the porous carbon flake network. When evaluated as an anode material for lithium-ion batteries, an excellent reversible capacity is achieved of 868 mA h g-1 at 0.2 A g-1 over 300 cycles and 668 mA h g-1 at 1 A g-1 over 500 cycles, indicating a high tolerance to the volume expansion. The approach investigated opens up new avenues for the design of high performance electrodes with highly cross-linked nanoflake structures, which may have great application prospects. PMID- 27684327 TI - Use of a Low-flow Digital Anesthesia System for Mice and Rats. AB - A traditional vaporizer depends on flowing gas and atmospheric pressure for passive anesthetic vaporization. Newly developed direct injection vaporizers utilize a syringe pump to directly administer volatile anesthetics into a gas stream. Unlike a traditional vaporizer, it can be used at very low flow rates, making it ideal for use on mice and rats. The equipment's capability to use low flow rates could result in a substantial cost savings due to the reduced need for anesthetic agents, compressed gas, and charcoal scavenging filters(1). A lower flow rate means less waste of anesthetic gas and likely reduces the risk of anesthetic exposure to laboratory personnel. Thus, the high levels of precision and safety associated with direct injection vaporizers, along with a reduced need for anesthetic agents, compressed gas, and charcoal filters are beneficial for research requiring small animal anesthesia. The goal of this protocol is to demonstrate the use of a syringe-driven direct injection vaporizer as part of a digital, low-flow anesthesia system. The direct injection vaporizer is capable of accurately delivering anesthesia at very low flow rates compared to a traditional vaporizer, making it a promising alternative for controlled gas anesthetic delivery to rodents. PMID- 27684328 TI - Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency. AB - Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters. Much of the estrogenic potency of wastewater treatment plant (WWTP) effluents can be attributed to the discharge of steroid estrogens including estradiol (E2), EE2 and E1 due to incomplete removal of these substances at the treatment plant. An evaluation of the efficacy of wastewater treatment processes requires the quantitative determination of individual substances most often undertaken using chemical analysis methods. Most frequently used methods include Gas Chromatography-Mass Spectrometry (GCMS/MS) or Liquid Chromatography-Mass Spectrometry (LCMS/MS) using multiple reaction monitoring (MRM). Although very useful for regulatory purposes, targeted chemical analysis can only provide data on the compounds (and specific metabolites) monitored. Ecotoxicology methods additionally ensure that any by-products produced or unknown estrogenic compounds present are also assessed via measurement of their biological activity. A number of in vitro bioassays including the Yeast Estrogen Screen (YES) are available to measure the estrogenic activity of wastewater samples. Chemical analysis in conjunction with in vivo and in vitro bioassays provides a useful toolbox for assessment of the efficacy and suitability of wastewater treatment processes with respect to estrogenic endocrine disrupting compounds. This paper utilizes a battery of chemical and ecotoxicology tests to assess conventional, advanced and emerging wastewater treatment processes in laboratory and field studies. PMID- 27684329 TI - Epidemiological and molecular investigation of a rubella outbreak, Romania, 2011 to 2012. AB - We describe a rubella outbreak that occurred in Romania between September 2011 and December 2012. During this period 24,627 rubella cases, 41.1% (n=10,134) of which female, were notified based on clinical criteria, and a total of 6,182 individuals were found serologically positive for IgM-specific rubella antibody. The median age of notified cases was 18 years (range: <1-65) and the most affected age group 15 to 19 years (n=16,245 cases). Of all notified cases, 24,067 cases (97.7%) reported no history of vaccination. Phylogenetic analysis of 19 sequences (739 nucleotides each), from 10 districts of the country revealed that the outbreak was caused by two distinct rubella virus strains of genotype 2B, which co-circulated with both temporal and geographical overlap. In addition to the 6,182 IgM-positive rubella cases, 28 cases of congenital rubella syndrome (CRS) were identified, including 11 neonatal deaths and one stillbirth. The outbreak underscores the need to encourage higher vaccination uptake in the population, particularly in women of reproductive age, and to strengthen epidemiological and laboratory investigations of suspected rubella cases. Genetic characterisation of wild-type rubella virus is an essential component to enhance surveillance and here we report rubella virus sequences from Romania. PMID- 27684330 TI - In Situ Synthesis of Fluorescent Carbon Dots/Polyelectrolyte Nanocomposite Microcapsules with Reduced Permeability and Ultrasound Sensitivity. AB - Designing and fabricating multifunctional nanocomposite microcapsules are considerable interests in both academic and industrial research aspects. This work first reports an innovative approach to in situ synthesize and assemble fluorescent carbon dots (CDs) into polyelectrolyte microcapsules, obtaining highly biocompatible nanocomposite microcapsules with excellent luminescence that facilitate imaging and identification in vitro, yet with the feasibility to load small molecules and ultrasound responsiveness to trigger their release. CDs are produced in situ in (PAH/PSS)4 microcapsule shells by carbonization of dextran molecules under relatively mild hydrothermal treatment. Compared with the collapsed and film-like (PAH/PSS)4 microcapsules, the novel composite microcapsules show a free-standing structure, smaller size, and thicker shell. CDs are proven to be fabricated and embedded in PAH/PSS multilayers, and the formed PAH/PSS/CD microcapsules are endowed with strong luminescence, as verified by the transmission electron microscopy, fluorescence spectra, and confocal laser scanning microscopy results. The in situ formation of CDs in capsule shells also empowers these capsules with ultrasound responsiveness and reduced permeability. The feasibility of encapsulation of small molecules (rhodamine B) and ultrasound triggered release is also shown. Most importantly, due to the intrinsic biocompatible property and photostability of CDs, these fluorescent PAH/PSS/CD microcapsules show negligible cell toxicity and low photobleaching, which are impossible for capsules composited with conventional organic dyes and semiconductor quantum dots. PMID- 27684331 TI - Time to take sexually transmitted infections seriously. PMID- 27684332 TI - Yellow fever vaccination coverage heterogeneities in Luanda province, Angola. PMID- 27684333 TI - An international registry for women exposed to Zika virus during pregnancy: time for answers. PMID- 27684334 TI - Ceftazidime-avibactam in ceftazidime-resistant infections. PMID- 27684335 TI - Ceftazidime-avibactam in ceftazidime-resistant infections. PMID- 27684336 TI - Plasmid-mediated colistin resistance in a patient infected with Klebsiella pneumoniae. PMID- 27684337 TI - Strategies of hospital antimicrobial stewardship associated with different health outcomes. PMID- 27684338 TI - Economic value of procalcitonin guidance. PMID- 27684339 TI - Influenza vaccine for international mass gatherings. PMID- 27684340 TI - Global burden of cutaneous leishmaniasis. PMID- 27684342 TI - The Middle East and hepatitis C virus infection: does it need special attention? PMID- 27684343 TI - Reconstruction of the hepatitis C virus epidemic in the USA. PMID- 27684341 TI - Further evidence to support the individualised treatment of gonorrhoea with ciprofloxacin. PMID- 27684344 TI - New data back early hypothesis for infectious microcephaly. PMID- 27684345 TI - Progress and pitfalls in prevention at AIDS 2016. PMID- 27684346 TI - Starting from scratch-the unique neglect of mycetoma. PMID- 27684352 TI - Non-destructive imaging of fragments of historical beeswax seals using high contrast X-ray micro-radiography and micro-tomography with large area photon counting detector array. AB - Historical beeswax seals are unique cultural heritage objects. Unfortunately, a number of historical sealing waxes show a porous structure with a strong tendency to stratification and embrittlement, which makes these objects extremely prone to mechanical damage. The understanding of beeswax degradation processes therefore plays an important role in the preservation and consequent treatment of these objects. Conventional methods applied for the investigation of beeswax materials (e.g. gas chromatography) are of a destructive nature or bring only limited information about the sample surface (microscopic techniques). Considering practical limitations of conventional methods and ethical difficulties connected with the sampling of the historical material, radiation imaging methods such as X ray micro-tomography presents a promising non-destructive tool for the onward scientific research in this field. In this contribution, we present the application of high-contrast X-ray micro-radiography and micro-tomography for the investigation of beeswax seal fragments. The method is based on the application of the large area photon-counting detector recently developed at our institute. The detector combines the advantages of single-photon counting technology with a large field of view. The method, consequently, enables imaging of relatively large objects with high geometrical magnification. In the reconstructed micro tomographies of investigated historical beeswax seals, we are able to reveal morphological structures such as stratification, micro-cavities and micro fractures with spatial resolution down to 5MUm non-destructively and with high imaging quality. The presented work therefore demonstrates that a combination of state-of-the-art hybrid pixel semiconductor detectors and currently available micro-focus x-ray sources makes it possible to apply X-ray micro-radiography and micro-tomography as a valuable non-destructive tool for volumetric beeswax seal morphological studies. PMID- 27684351 TI - Adductomics Pipeline for Untargeted Analysis of Modifications to Cys34 of Human Serum Albumin. AB - An important but understudied class of human exposures is comprised of reactive electrophiles that cannot be measured in vivo because they are short-lived. An avenue for assessing these meaningful exposures focuses on adducts from reactions with nucleophilic loci of blood proteins, particularly Cys34 of human serum albumin, which is the dominant scavenger of reactive electrophiles in serum. We developed an untargeted analytical scheme and bioinformatics pipeline for detecting, quantitating, and annotating Cys34 adducts in tryptic digests of human serum/plasma. The pipeline interrogates tandem mass spectra to find signatures of the Cys34-containing peptide, obtains accurate masses of putative adducts, quantitates adduct levels relative to a "housekeeping peptide", and annotates modifications based on a combination of retention time, accurate mass, elemental composition, and database searches. We used the adductomics pipeline to characterize 43 adduct features in archived plasma from healthy human subjects and found several that were highly associated with smoking status, race, and other covariates. Since smoking is a strong risk factor for cancer and cardiovascular disease, our ability to discover adducts that distinguish smokers from nonsmokers with untargeted adductomics indicates that the pipeline is suitable for use in epidemiologic studies. In fact, adduct features were both positively and negatively associated with smoking, indicating that some adducts arise from reactions between Cys34 and constituents of cigarette smoke (e.g., ethylene oxide and acrylonitrile) while others (Cys34 oxidation products and disulfides) appear to reflect alterations in the serum redox state that resulted in reduced adduct levels in smokers. PMID- 27684353 TI - Autoxidation Products of Betulonaldehyde. AB - Three major degradation products resulted from the exposure of betulonaldehyde (1) to air in solution at room temperature. From HRMS and NMR data, the products, which were isolated by preparative supercritical fluid chromatography (SFC), were identified as betulonic acid (2) and C-17 hydroperoxide epimers 3 (beta-OOH) and 4 (alpha-OOH). For 3 and 4, the H-18 multiplet pattern of the isolated products established the configuration at C-17. PMID- 27684354 TI - Cost-utility analysis of physician-pharmacist collaborative intervention for treating hypertension compared with usual care. AB - OBJECTIVE: To estimate long-term costs and outcomes attributable to a physician pharmacist collaborative intervention compared with physician management alone for treating essential hypertension. METHODS: A Markov model cohort simulation with a 6-month cycle length to predict acute coronary syndrome, stroke, and heart failure throughout lifetime was performed. A cohort of 399 patients was obtained from two prospective, cluster randomized controlled clinical trials implementing physician-pharmacist collaborative interventions in community-based medical offices in the Midwest, USA. Framingham risk equations and other algorithms were used to predict the vascular diseases. SBP reduction due to the interventions deteriorated until 5 years. Direct medical costs using a payer perspective were adjusted to 2015 dollar value, and the main outcome was quality-adjusted life years (QALYs); both were discounted at 3%. The intervention costs were estimated from the trials, whereas the remaining parameters were from published studies. A series of sensitivity analyses including changing patient risks of vascular diseases, probabilistic sensitivity analysis, and a cost-effectiveness acceptability curve were performed. RESULTS: The lifetime incremental costs were $26 807.83 per QALY (QALYs gained = 0.14). The intervention provided the greatest benefit for the high-risk patients, moderate benefit for the trial patients, and the lowest benefit for the low-risk patients. If a payer is willing to pay $50 000 per QALY gained, in 48.6% of the time the intervention would be cost effective. CONCLUSION: Team-based care such as a physician-pharmacist collaboration appears to be a cost-effective strategy for treating hypertension. The intervention is most cost-effective for high-risk patients. PMID- 27684355 TI - Assays for the Degradation of Misfolded Proteins in Cells. AB - Protein misfolding and aggregation are associated with various neurodegenerative diseases. Cellular mechanisms that recognize and degrade misfolded proteins may serve as potential therapeutic targets. To distinguish degradation of misfolding prone proteins from other mechanisms that regulate their levels, one important method is to measure protein half-life in cells. However, this can be challenging because misfolding-prone proteins may exist in different forms, including the native form and misfolded forms of distinct characteristics. Here we describe assays to examine the half-life of misfolded proteins in mammalian cells using a highly aggregation-prone protein, Ataxin-1 with an extended polyglutamine (polyQ) stretch, and a conformationally unstable luciferase mutant as models. Cycloheximide chase is combined with cell fractionation to examine the turnover rate of misfolding-prone proteins in various cellular fractions. We further depict a fluorescence-based assay using an enhanced green fluorescence protein (EGFP)-fusion of the luciferase mutant, which can be adapted for high throughput screening on a microplate-reader. PMID- 27684357 TI - Systemic vasculitis and the gut. AB - PURPOSE OF REVIEW: Gastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed. RECENT FINDINGS: Diagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield. There are conflicting reports on the association of antineutrophilic cytoplasmic antibodies (ANCA) type with the frequency of gastrointestinal involvement in ANCA-associated vasculitis. Pancreatitis is a rare but serious complication of ANCA-associated vasculitis. Terminal ileitis may be observed in immunoglobulin A vasculitis and can be hard to distinguish from Crohn's disease. High fecal calprotectin levels can indicate active gastrointestinal involvement in both immunoglobulin A vasculitis and Behcet's syndrome. Refractory gastrointestinal involvement in Behcet's syndrome can be treated with thalidomide and/or TNF-alpha antagonists. The outcome of mesenteric vasculitis in systemic lupus erythematosus can be improved with high-dose glucocorticoids and cyclophosphamide or rituximab. SUMMARY: Gastrointestinal system can be commonly involved in immunoglobulin A vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, and Behcet's syndrome and can be an important cause of morbidity and mortality. Treatment depends on the type of vasculitis and is usually with high-dose corticosteroids and immunosuppressives. PMID- 27684358 TI - Behcet's syndrome in nonendemic regions. AB - PURPOSE OF REVIEW: Behcet's syndrome is more common in certain geographic regions, however, can be seen outside of these areas and need to be included in the differential diagnosis of many patients, as it has overlapping features with many rheumatologic conditions. RECENT FINDINGS: Especially in regions with immigrant populations, there seem to be similarities to originating countries in Behcet's prevalence, but the syndrome is not limited to those from certain backgrounds and can be seen in others also. There is emerging evidence that even though the prevalence of Behcet's may be similar to that of endemic areas, in nonendemic regions the condition may be less severe, suggesting potential environment agents in determining the severity of the disease. In addition, women seem to be overrepresented in nonendemic areas and may explain part of the reason for less severe symptoms, as Behcet's tends to be more severe in men. SUMMARY: The somewhat different presentation of Behcet's syndrome in nonendemic areas needs to be considered when thinking about Behcet's in the differential diagnosis of patients. Research into potentially less severe form of the disease in nonendemic areas may provide new clues to the pathogenesis of this condition. PMID- 27684359 TI - Extent of Resection and Survival in Glioblastoma Multiforme. PMID- 27684356 TI - A Comprehensive Review of Topical Odor-Controlling Treatment Options for Chronic Wounds. AB - The process of wound healing is often accompanied by bacterial infection or critical colonization, resulting in protracted inflammation, delayed reepithelization, and production of pungent odors. The malodor produced by these wounds may lower health-related quality of life and produce psychological discomfort and social isolation. Current management focuses on reducing bacterial activity within the wound site and absorbing malodorous gases. For example, charcoal-based materials have been incorporated into dressing for direct adsorption of the responsible gases. In addition, multiple topical agents, including silver, iodine, honey, sugar, and essential oils, have been suggested for incorporation into dressings in an attempt to control the underlying bacterial infection. This review describes options for controlling malodor in chronic wounds, the benefits and drawbacks of each topical agent, and their mode of action. We also discuss the use of subjective odor evaluation techniques to assess the efficacy of odor-controlling therapies. The perspectives of employing novel biomaterials and technologies for wound odor management are also presented. PMID- 27684360 TI - Chemical treatment and chitosan coating of yeast cells to improve the encapsulation and controlled release of bovine serum albumin. AB - We investigate the encapsulation of bovine serum albumin (BSA) in chemical treated and chitosan-coated yeast cells, Saccharomyces cerevisiae (S. cerevisiae), for the controlled release of BSA. The chemical treatment can sufficiently enlarge the small-sized cell-wall cavities and/or break the integrity for the entrance of BSA to the interior of yeast cells, and the additional chitosan coating can well prevent the rapid release of encapsulated BSA from the yeast-derived microcapsules. The sodium hydroxide pretreated S. cerevisiae gives a maximum encapsulation yield of (10.1 +/- 0.2)% for BSA. An additional coating of S. cerevisiae with chitosan can reduce the initial burst release of BSA and extend the release period from 24 h in the chitosan-free case to 48 h in phosphate buffer at pH 7.4. The prepared microcapsules can well keep the shapes and sizes of yeast cells and thus show uniform sizes of 3.85 +/- 0.81 MUm. The encapsulated BSA well retains its pristine ultraviolet spectroscopic and chromatographic behaviors. The present microencapsulation protocol has the advantages of convenient and mild operation, high encapsulation efficiency, and organic solvent-free nature, which is of reference value for establishing high performance controllable biomacromolecule-delivery systems. PMID- 27684361 TI - Prosthetic Voice Rehabilitation Following Laryngectomy: It's the Archer Not the Arrow. PMID- 27684362 TI - Preemptive strikes: Fear, hope, and defensive aggression. AB - Preemptive strikes are costly and harmful. Existing models of defensive aggression focus narrowly on the role fear plays in motivating preemptive strikes. Theoretically integrating the literatures on conflict, decision making, and emotion, the current research investigated how specific emotions associated with certainty or uncertainty, including fear, anger, disgust, hope, and happiness, influence preemptive strikes. Study 1 demonstrated that hope negatively predicts defensive exits from relationships in choice dilemmas. Studies 2 and 3 experimentally manipulated risk of being attacked in an incentivized, interactive decision making task-the Preemptive Strike Game. Risk of being attacked fueled preemptive strikes; reduced feelings of hope partially mediated this effect in Study 3. Studies 4 and 5 investigated preemptive strikes under uncertainty (rather than risk). In Study 4, reasoning about the factors that make one trustful of others curbed preemptive strikes; cogitating about the factors that underlie discrete emotions, however, did not influence defensive aggression. Study 5 demonstrated that the valence and uncertainty appraisals of incidental emotions interact in shaping preemptive strikes. Specifically, recalling an autobiographical emotional experience that produced hope significantly decreased attack rates relative to fear, happiness, and a control condition. Fear, anger, disgust, and happiness were either unrelated to preemptive strikes or showed inconsistent relationships with preemptive strikes across the 5 studies. These findings shed light on how emotions shape defensive aggression, advance knowledge on strategic choice under risk and uncertainty, and demonstrate hope's positive effects on social interactions and relationships. (PsycINFO Database Record PMID- 27684363 TI - Romantic relationships in the ecosystem: Compassionate goals, nonzero-sum beliefs, and change in relationship quality. AB - According to the egosystem-ecosystem theory of social motivation, people with ecosystem motivation believe their interpersonal relationships work in nonzero sum ways. A longitudinal study of individuals in romantic relationships and a study of romantic couples who had a conflict discussion in the laboratory both showed that compassionate goals predict increased nonzero-sum beliefs through increased responsiveness and perceptions of partner's responsiveness and that nonzero-sum beliefs uniquely predict increased relationship quality through increased optimism that relationship problems can be overcome. The results support the view that motivational orientations shape people's lay theories that their relationship works in zero-sum or nonzero-sum ways, and further show that nonzero-sum beliefs are an important and unique predictor of change in relationship quality independent of responsiveness or perceived partner responsiveness. (PsycINFO Database Record PMID- 27684364 TI - Influence of indirect information on interpersonal trust despite direct information. AB - Trust is integral to successful relationships. The development of trust stems from how one person treats others, and there are multiple ways to learn about someone's trust-relevant behavior. The present research captures the development of trust to examine if trust-relevant impressions and behavior are influenced by indirect behavioral information (i.e., descriptions of how a person treated another individual)-even in the presence of substantial direct behavioral information (i.e., self-relevant, first-hand experience with a person). Participants had repeated interpersonal exchanges with a partner who was trustworthy or untrustworthy with participants' money. The present studies vary the frequency with which (Studies 1 & 2), the order in which (Study 3) and the number of people for whom (Study 4) indirect information (i.e., brief vignettes describing trustworthy or untrustworthy behavior) were presented. As predicted, across 4 studies, we observed a robust effect of indirect-information despite the presence of substantial direct information. Even after dozens of interactions in which a partner betrayed (or not), a brief behavioral description of a partner influenced participants' willingness to actually trust the partner with money, memory-based estimates of partner-behavior, and impressions of the partner. These effects were observed even though participants were also sensitive to partners' actual trust behavior, and even when indirect behavioral descriptions were only presented a single time. Impressions were identified as a strong candidate mechanism for the effect of indirect-information on behavior. We discuss implications of the persistence of indirect information for impression formation, relationship development, and future studies of trust. (PsycINFO Database Record PMID- 27684365 TI - Exercise cardiac power and the risk of coronary heart disease and cardiovascular mortality in men. AB - PURPOSE: The aim of this study was to examine the relationship of exercise cardiac power (ECP), defined as a ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, with the risk of mortality from coronary heart diseases (CHD) and cardiovascular diseases (CVD). DESIGN: Population-based cohort study with an average follow-up of 25 years from eastern Finland. About 2358 men at baseline participated in exercise stress test and 182 CHD and 302 CVD deaths occurred. RESULTS: Men with low ECP (< 8.7 mL/mmHg, lowest quartile) had a 3.5-fold (95% CI 2.1-5.8, p < 0.0001) risk of CHD mortality as compared with men with high ECP (>16.4 mL/mmHg, highest quartile) after adjusting for age and examination year. Low ECP was associated with a 2.8 fold risk of CHD and 2.4-fold for CVD mortality after additional adjustment for conventional risk factors. After further adjustment for leisure time physical activity, the results hardly changed (HR 2.5, 95% CI 1.71-3.67, p < 0.001). CONCLUSION: ECP provides non-invasive and easily available measure for the prediction of CHD and CVD mortality. One of the most potential explanation for the association between ECP and the risk of CHD and CVD mortality is an elevated afterload and peripheral resistance indicated by hypertension. Key messages Index of exercise cardiac power defined as the ratio of directly measured maximal oxygen uptake (VO2max) with peak systolic blood pressure gives prognostic information in coronary heart disease (CHD) and CVD mortality risk stratification. ECP provides non-invasive and easily available measure for the prediction of CHD and CVD mortality. One of the most potential explanation for the association between ECP and the risk of CHD and CVD mortality is an elevated afterload and peripheral resistance indicated by hypertension. PMID- 27684366 TI - Chronic subdural haematomas in elderly population. Neurosurgical aspects and focus on the single-burr hole technique performed under assisted local anaesthesia. AB - OBJECTIVE: Chronic subdural haematomas (CSDH) is a common pathology that usually affects the elderly population. The incidence of CSDH has recently been increasing with the expansion of the aging population. The objective of our study was to evaluate the outcome following surgical drainage of CSDH in elderly patients. MATERIALS AND METHODS: We performed a retrospective analysis of 455 consecutive patients with CSDHs over a 5-year period. Among them, all 121 patients older than 80-year old were included in the study. Clinical status, comorbidities, type of surgical technique and outcome were analyzed. Outcome at last follow-up was measured using the Markwalder grading score and the Glasgow outcome scale. RESULTS: Patients ranged from 80- to 94-year old with a median age of 84 years (range 80-94). Ninety-eight percent of patients were surgically treated by a small burr hole under assisted local anaesthesia. About 69.2% of patients improved post-operatively. The mortality rate was 6.8%. CONCLUSION: CSDH is a common pathology in the elderly population. Patients with CSDHs often have comorbodities that need to be considered in deciding whether surgical treatment is indicated. When surgery is elected, small craniostomy techniques performed under assisted local anesthesia is safe and should be favored in this frail population. PMID- 27684367 TI - RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila. AB - Neuronal computation underlying detection of visual motion has been studied for more than a half-century. In Drosophila, direction-selective T4/T5 neurons show supralinear signal amplification in response to stimuli moving in their preferred direction, in agreement with the prediction made by the Hassenstein-Reichardt detector. Nevertheless, the molecular mechanism explaining how the Hassenstein Reichardt model is implemented in T4/T5 cells has not been identified yet. In the present study, we utilized cell type-specific transcriptome profiling with RNA seq to obtain a complete gene expression profile of T4/T5 neurons. We analyzed the expression of genes that affect neuronal computational properties and can underlie the molecular implementation of the core features of the Hassenstein Reichardt model to the dendrites of T4/T5 neurons. Furthermore, we used the acquired RNA-seq data to examine the neurotransmitter system used by T4/T5 neurons. Surprisingly, we observed co-expression of the cholinergic markers and the vesicular GABA transporter in T4/T5 neurons. We verified the previously undetected expression of vesicular GABA transporter in T4/T5 cells using VGAT LexA knock-in line. The provided gene expression dataset can serve as a useful source for studying the properties of direction-selective T4/T5 neurons on the molecular level. PMID- 27684368 TI - Indication of Horizontal DNA Gene Transfer by Extracellular Vesicles. AB - The biological relevance of extracellular vesicles (EV) in intercellular communication has been well established. Thus far, proteins and RNA were described as main cargo. Here, we show that EV released from human bone marrow derived mesenchymal stromal cells (BM-hMSC) also carry high-molecular DNA in addition. Extensive EV characterization revealed this DNA mainly associated with the outer EV membrane and to a smaller degree also inside the EV. Our EV purification protocol secured that DNA is not derived from apoptotic or necrotic cells. To analyze the relevance of EV-associated DNA we lentivirally transduced Arabidopsis thaliana-DNA (A.t.-DNA) as indicator into BM-hMSC and generated EV. Using quantitative polymerase chain reaction (qPCR) techniques we detected high copy numbers of A.t.-DNA in EV. In recipient hMSC incubated with tagged EV for two weeks we identified A.t.-DNA transferred to recipient cells. Investigation of recipient cell DNA using quantitative PCR and verification of PCR-products by sequencing suggested stable integration of A.t.-DNA. In conclusion, for the first time our proof-of-principle experiments point to horizontal DNA transfer into recipient cells via EV. Based on our results we assume that eukaryotic cells are able to exchange genetic information in form of DNA extending the known cargo of EV by genomic DNA. This mechanism might be of relevance in cancer but also during cell evolution and development. PMID- 27684370 TI - Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology. AB - Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice. PMID- 27684369 TI - Testing the Role of Dorsal Premotor Cortex in Auditory-Motor Association Learning Using Transcranical Magnetic Stimulation (TMS). AB - Interactions between the auditory and the motor systems are critical in music as well as in other domains, such as speech. The premotor cortex, specifically the dorsal premotor cortex (dPMC), seems to play a key role in auditory-motor integration, and in mapping the association between a sound and the movement used to produce it. In the present studies we tested the causal role of the dPMC in learning and applying auditory-motor associations using 1 Hz repetitive Transcranical Magnetic Stimulation (rTMS). In this paradigm, non-musicians learn a set of auditory-motor associations through melody training in two contexts: first when the sound to key-press mapping was in a conventional sequential order (low to high tones mapped onto keys from left to right), and then when it was in a novel scrambled order. Participant's ability to match the four pitches to four computer keys was tested before and after the training. In both experiments, the group that received 1 Hz rTMS over the dPMC showed no significant improvement on the pitch-matching task following training, whereas the control group (who received rTMS to visual cortex) did. Moreover, in Experiment 2 where the pitch key mapping was novel, rTMS over the dPMC also interfered with learning. These findings suggest that rTMS over dPMC disturbs the formation of auditory-motor associations, especially when the association is novel and must be learned rather explicitly. The present results contribute to a better understanding of the role of dPMC in auditory-motor integration, suggesting a critical role of dPMC in learning the link between an action and its associated sound. PMID- 27684371 TI - Personality Traits Are Associated with Research Misbehavior in Dutch Scientists: A Cross-Sectional Study. AB - BACKGROUND: Personality influences decision making and ethical considerations. Its influence on the occurrence of research misbehavior has never been studied. This study aims to determine the association between personality traits and self reported questionable research practices and research misconduct. We hypothesized that narcissistic, Machiavellianistic and psychopathic traits as well as self esteem are associated with research misbehavior. METHODS: Included in this cross sectional study design were 535 Dutch biomedical scientists (response rate 65%) from all hierarchical layers of 4 university medical centers in the Netherlands. We used validated personality questionnaires such as the Dark Triad (narcissism, psychopathy, and Machiavellianism), Rosenberg's Self-Esteem Scale, the Publication Pressure Questionnaire (PPQ), and also demographic and job-specific characteristics to investigate the association of personality traits with a composite research misbehavior severity score. FINDINGS: Machiavellianism was positively associated (beta 1.28, CI 1.06-1.53) with self-reported research misbehavior, while narcissism, psychopathy and self-esteem were not. Exploratory analysis revealed that narcissism and research misconduct were more severe among persons in higher academic ranks (i.e., professors) (p<0.01 and p<0.001, respectively), and self-esteem scores and publication pressure were lower (p<0.001 and p<0.01, respectively) as compared to postgraduate PhD fellows. CONCLUSIONS: Machiavellianism may be a risk factor for research misbehaviour. Narcissism and research misbehaviour were more prevalent among biomedical scientists in higher academic positions. These results suggest that personality has an impact on research behavior and should be taken into account in fostering responsible conduct of research. PMID- 27684372 TI - Distribution and Outcomes of a Phenotype-Based Approach to Guide COPD Management: Results from the CHAIN Cohort. AB - RATIONALE: The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. OBJECTIVE: We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. METHODS: We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. RESULTS: Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1+/-8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. CONCLUSIONS: There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use. PMID- 27684373 TI - How Nectar-Feeding Bats Localize their Food: Echolocation Behavior of Leptonycteris yerbabuenae Approaching Cactus Flowers. AB - Nectar-feeding bats show morphological, physiological, and behavioral adaptations for feeding on nectar. How they find and localize flowers is still poorly understood. While scent cues alone allow no precise localization of a floral target, the spatial properties of flower echoes are very precise and could play a major role, particularly at close range. The aim of this study is to understand the role of echolocation for classification and localization of flowers. We compared the approach behavior of Leptonycteris yerbabuenae to flowers of a columnar cactus, Pachycereus pringlei, to that to an acrylic hollow hemisphere that is acoustically conspicuous to bats, but has different acoustic properties and, contrary to the cactus flower, present no scent. For recording the flight and echolocation behaviour we used two infrared video cameras under stroboscopic illumination synchronized with ultrasound recordings. During search flights all individuals identified both targets as a possible food source and initiated an approach flight; however, they visited only the cactus flower. In experiments with the acrylic hemisphere bats aborted the approach at ca. 40-50 cm. In the last instant before the flower visit the bats emitted a long terminal group of 10 20 calls. This is the first report of this behaviour for a nectar-feeding bat. Our findings suggest that L. yerbabuenae use echolocation for classification and localization of cactus flowers and that the echo-acoustic characteristics of the flower guide the bats directly to the flower opening. PMID- 27684374 TI - Vascular Dysfunction in Horses with Endocrinopathic Laminitis. AB - Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10-9-10-5M) and 5-hydroxytryptamine (5HT; 10-9-10-5M) and the vasodilator acetylcholine (10-9-10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 +/- 94.1% v EL 90.8 +/- 4.4%, P = 0.01, laminar veins 129.4 +/- 14.8% v EL 71.2 +/- 4.1%, P = 0.005 and facial skin arteries 182.0 +/- 40.7% v EL 91.4 +/- 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof. PMID- 27684375 TI - Alternative Isoform Analysis of Ttc8 Expression in the Rat Pineal Gland Using a Multi-Platform Sequencing Approach Reveals Neural Regulation. AB - Alternative isoform regulation (AIR) vastly increases transcriptome diversity and plays an important role in numerous biological processes and pathologies. However, the detection and analysis of isoform-level differential regulation is difficult, particularly in the face of complex and incompletely-annotated transcriptomes. Here we have used Illumina short-read/high-throughput RNA-Seq to identify 55 genes that exhibit neurally-regulated AIR in the pineal gland, and then used two other complementary experimental platforms to further study and characterize the Ttc8 gene, which is involved in Bardet-Biedl syndrome and non syndromic retinitis pigmentosa. Use of the JunctionSeq analysis tool led to the detection of several novel exons and splice junctions in this gene, including two novel alternative transcription start sites which were found to display disproportionately strong neurally-regulated differential expression in several independent experiments. These high-throughput sequencing results were validated and augmented via targeted qPCR and long-read Pacific Biosciences SMRT sequencing. We confirmed the existence of numerous novel splice junctions and the selective upregulation of the two novel start sites. In addition, we identified more than 20 novel isoforms of the Ttc8 gene that are co-expressed in this tissue. By using information from multiple independent platforms we not only greatly reduce the risk of errors, biases, and artifacts influencing our results, we also are able to characterize the regulation and splicing of the Ttc8 gene more deeply and more precisely than would be possible via any single platform. The hybrid method outlined here represents a powerful strategy in the study of the transcriptome. PMID- 27684376 TI - A study of physical activity comparing people with Charcot-Marie-Tooth disease to normal control subjects. AB - PURPOSE: Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. METHODS: We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. RESULTS: Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. CONCLUSION: The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: * People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. * Compared to healthy controls, people with Charcot-Marie-Tooth disease had a lower step count over seven days, but exhibited more frequent transitions from sedentary to active behaviors * High Body Mass Index and increased time spent sedentary were related factors that have implications for general health status. * Understanding the profile of physical activity and behavior can allow targeting of rehabilitation interventions to address mobility and fitness. PMID- 27684377 TI - Impact of Reed Canary Grass Cultivation and Mineral Fertilisation on the Microbial Abundance and Genetic Potential for Methane Production in Residual Peat of an Abandoned Peat Extraction Area. AB - This study examined physiochemical conditions and prokaryotic community structure (the bacterial and archaeal 16S rRNA genes and mcrA gene abundances and proportions), and evaluated the effect of reed canary grass cultivation and mineral fertilisation on these factors, in the 60 cm thick residual peat layer of experimental plots located on an abandoned peat extraction area. The archaeal proportion was 0.67-39.56% in the prokaryotic community and the methanogens proportion was 0.01-1.77% in the archaeal community. When bacterial abundance was higher in the top 20 cm of peat, the archaea were more abundant in the 20-60 cm layer and methanogens in the 40-60 cm layer of the residual peat. The bacterial abundance was significantly increased, but archaeal abundance was not affected by cultivation. The fertiliser application had a slight effect on peat properties and on archaeal and methanogen abundances in the deeper layer of cultivated peat. The CH4 emission was positively related to mcrA abundance in the 20-60 cm of the bare peat, while in case of reed canary grass cultivation these two parameters were not correlated. Reed canary grass cultivation mitigated CH4 emission, although methanogen abundance remained approximately the same or even increased in different layers of residual peat under cultivated sites over time. This study supports the outlook of using abandoned peat extraction areas to produce reed canary grass for energy purposes as an advisable land-use practice from the perspective of atmospheric impact in peatland-rich Northern Europe. PMID- 27684378 TI - Obstructive Sleep Apnea Is Associated with Elevated High Sensitivity C-Reactive Protein Levels Independent of Obesity: Korean Genome and Epidemiology Study. AB - Obstructive sleep apnea syndrome (OSA) has been recognized as a common health problem, and increasing obesity rates have led to further remarkable increases in the prevalence of OSA, along with more prominent cardiovascular morbidities. Though previous studies have reported an independent relationship between elevated high sensitivity C-reactive protein (hsCRP) levels and OSA, the issue remains controversial owing to inadequate consideration of obesity and various confounding factors. So far, few population based studies of association between OSA and hsCRP levels have been published. Therefore, the purpose of the present study was to investigate whether OSA is associated with increased hsCRP levels independent of obesity in a large population-based study. A total of 1,835 subjects (968 men and 867 women) were selected from a larger cohort of the ongoing Korean Genome and Epidemiology Study (KoGES). Overnight polysomnography was performed on each participant. All participants underwent anthropometric measurements and biochemical analyses, including analysis of lipid profiles and hsCRP levels. Based on anthropometric data, body mass index (BMI) and waist hip ratio (WHR) were calculated and fat mass (FM) were measured by means of multi frequency bioelectrical impedance analysis (BIA). Mild OSA and moderate to severe OSA were defined by an AHI >5 and >=15, respectively. The population was sub divided into 3 groups based on the tertile cut-points for the distribution of hsCRP levels. The percentage of participants in the highest tertile of hsCRP increased dose-dependently according to the severity of OSA. After adjustment for potential confounders and obesity-related variables (BMI, WHR, and body fat) in a multiple logistic model, participants with moderate to severe OSA had 1.73-, 2.01 , and 1.61-fold greater risks of being in the highest tertile of hsCRP levels than participants with non-OSA, respectively. Interaction between obesity (BMI >=25kg/m2) and the presence of moderate-to-severe OSA was significant on the middle tertile levels of hsCRP (OR = 2.4), but not on the highest tertile, compared to the lowest tertile. OSA is independently associated with elevated hsCRP levels and may reflect an increased risk for cardiovascular morbidity. However, we found that OSA and obesity interactively contribute to individuals with general levels of hsCRP (<1.01 mg/dl). The short-term and long-term effects of elevated hsCRP levels on cardiovascular risk in the context of OSA remain to be defined in future studies. PMID- 27684380 TI - Is it really good to talk? Testing the impact of providing concurrent verbal protocols on driving performance. AB - Questions have been raised regarding the impact that providing concurrent verbal protocols has on task performance in various settings; however, there has been little empirical testing of this in road transport. The aim of this study was to examine the impact of providing concurrent verbal protocols on driving performance. Participants drove an instrumented vehicle around a set route, twice whilst providing a concurrent verbal protocol, and twice without. A comparison revealed no differences in behaviour related to speed, braking and steering wheel angle when driving mid-block, but a significant difference in aspects of braking and acceleration at roundabouts. When not providing a verbal protocol, participants were found to brake harder on approach to a roundabout and accelerate more heavily coming out of roundabouts. It is concluded that providing verbal protocols may have a positive effect on braking and accelerating. Practical implications related to driver training and future research are discussed. Practitioner Summary: Verbal protocol analysis is used by ergonomists to understand aspects of cognition and decision-making during complex tasks such as driving and control room operation. This study examines the impact that it has on driving performance, providing evidence to support its continued use in ergonomics applications. PMID- 27684381 TI - Bilingual advantage, bidialectal advantage or neither? Comparing performance across three tests of executive function in middle childhood. AB - When bilinguals speak, both fluent language systems become activated in parallel and exert an influence on speech production. As a consequence of maintaining separation between the two linguistic systems, bilinguals are purported to develop enhanced executive control functioning. Like bilinguals, individuals who speak two dialects must also maintain separation between two linguistic systems, albeit to a lesser degree. Across three tests of executive function, we compared bilingual and bidialectal children's performance to that of a monolingual control group. No evidence for a bidialectal advantage was found. However, in line with a growing number of recent partial and failed replications, we observed a significant bilingual advantage only in one measure in one task. This calls the robustness of the bilingual advantage into question. A comprehensive review of studies investigating advantages of inhibitory control and cognitive flexibility in bilingual children reveals that the bilingual advantage is likely to be both task and sample specific, and the interaction between these factors makes qualification of the effect challenging. These findings highlight the importance of tracking the impact of dual linguistic systems across the lifespan using tasks calibrated for difficulty across different ages. PMID- 27684379 TI - Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. AB - BACKGROUND: To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood. METHODS: Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml. RESULTS: In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml. DISCUSSION: The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre emptive therapy. PMID- 27684383 TI - Role of self-reported hearing disability and measured hearing sensitivity in understanding participation restrictions and health-related quality of life: a study with hundred and three older adults with hearing loss. PMID- 27684382 TI - Assessing the real-world effect of laparoscopic bariatric surgery on the management of obesity-related comorbidities: A retrospective matched cohort study using a US Claims Database. AB - AIMS: To evaluate the real-world effect of laparoscopic bariatric surgery, comprising adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG), on the management of obesity-related comorbidities. METHODS: Patients who underwent laparoscopic bariatric surgeries between 2006 and 2013 were identified from the Optum Clinformatics administrative claims database. Those surgical patients were matched to medically managed patients (controls) on selected patient characteristics. Comorbidity management was assessed every 6 months up to 5 years after the surgery or an assigned index date for control subjects (follow-up), by evaluating the number of medication classes used to treat type 2 diabetes, hypertension and dyslipidaemia, as well as by evaluating the percentages of patients free of medications for these comorbidities. RESULTS: Patients who underwent LAGB (n = 4208, mean age 46.3 years), LRYGB (n = 4308, mean age 46.4 years) or LSG (n = 545, mean age 45.1 years) and patients in the control cohort (n = 9061, mean age 46.4 years) were similar in age, and the majority of patients in each study cohort were female (69.4%-75.8%). Compared with control subjects, patients who had laparoscopic bariatric surgery had significantly lower medication usage for obesity-related comorbidities, a trend that was evident at 6 months and that continued for up to 5 years of follow-up. Sub-analyses of changes in selected laboratory test values over follow-up corroborated the primary analyses. CONCLUSIONS: Patients who had laparoscopic bariatric surgery used fewer medications for type 2 diabetes, hypertension and dyslipidaemia and had significant improvement in cardiometabolic risk factors for up to 5 years of follow-up compared with matched control subjects. PMID- 27684384 TI - High Pneumocystis jirovecii colonization rate among haemodialysis patients. AB - Haemodialysis patients have been found to have an increased risk of developing Pneumocystis pneumonia (PcP) compared to the control population. To the best of our knowledge, no data are available on pulmonary colonization with Pneumocystis jirovecii in haemodialysis patients; therefore, the aim of this study was to determine the prevalence of pulmonary colonization with P. jirovecii in haemodialysis patients, and to find the related risk factors. Induced sputa of 62 haemodialysis patients were investigated using quantitative polymerase chain reaction for the presence of P. jirovecii. 20.9% of the patients were colonized with P. jirovecii and 46.2% of whom had CD4 cell counts below 400/MUl. There was no significant correlation between colonization and time on dialysis treatment. As haemodialysis patients seem to be at higher risk of PcP than the general population, doctors should be aware of the high rate of P. jirovecii colonization amongst them. Furthermore, colonized patients remain a potential source of transmission of P. jirovecii to other patients or to health care workers. PMID- 27684385 TI - Identification of pneumococcal proteins that are functionally linked to penicillin-binding protein 2b (PBP2b). AB - The oval shape of pneumococci results from a combination of septal and lateral peptidoglycan synthesis. The septal cross-wall is synthesized by the divisome, while the elongasome drives cell elongation by inserting new peptidoglycan into the lateral cell wall. Each of these molecular machines contains penicillin binding proteins (PBPs), which catalyze the final stages of peptidoglycan synthesis, plus a number of accessory proteins. Much effort has been made to identify these accessory proteins and determine their function. In the present paper we have used a novel approach to identify members of the pneumococcal elongasome that are functionally closely linked to PBP2b. We discovered that cells depleted in PBP2b, a key component of the elongasome, display several distinct phenotypic traits. We searched for proteins that, when depleted or deleted, display the same phenotypic changes. Four proteins, RodA, MreD, DivIVA and Spr0777, were identified by this approach. Together with PBP2b these proteins are essential for the normal function of the elongasome. Furthermore, our findings suggest that DivIVA, which was previously assigned as a divisomal protein, is required to correctly localize the elongasome at the negatively curved membrane region between the septal and lateral cell wall. PMID- 27684386 TI - Postoperative radiotherapy for non-small cell lung cancer. AB - BACKGROUND: The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) was not clear. A systematic review and individual participant data meta-analysis was undertaken to evaluate available evidence from randomised controlled trials (RCTs). These results were first published in Lung Cancer in 2013. OBJECTIVES: To evaluate the effects of PORT on survival and recurrence in patients with completely resected NSCLC. To investigate whether predefined patient subgroups benefit more or less from PORT. SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1965 to 8 July 2016) with information from trial registers, handsearching of relevant meeting proceedings and discussion with trialists and organisations. SELECTION CRITERIA: We included trials of surgery versus surgery plus radiotherapy, provided they randomised participants with NSCLC using a method that precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. We sought data on all participants from those responsible for the trial. We obtained updated individual participant data (IPD) on survival and date of last follow-up, as well as details on treatment allocation, date of randomisation, age, sex, histological cell type, stage, nodal status and performance status. To avoid potential bias, we requested information on all randomised participants, including those excluded from investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. MAIN RESULTS: We identified 14 trials evaluating surgery versus surgery plus radiotherapy. Individual participant data were available for 11 of these trials, and our analyses are based on 2343 participants (1511 deaths). Results show a significant adverse effect of PORT on survival, with a hazard ratio of 1.18, or an 18% relative increase in risk of death. This is equivalent to an absolute detriment of 5% at two years (95% confidence interval (CI) 2% to 9%), reducing overall survival from 58% to 53%. Subgroup analyses showed no differences in effects of PORT by any participant subgroup covariate.We did not undertake analysis of the effects of PORT on quality of life and adverse events. Investigators did not routinely collect quality of life information during these trials, and it was unlikely that any benefit of PORT would offset the observed survival disadvantage. We considered risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS: Results from 11 trials and 2343 participants show that PORT is detrimental to those with completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. Results of ongoing RCTs will clarify the effects of modern radiotherapy in patients with N2 tumours. PMID- 27684387 TI - The incorporation of fluoride and strontium in hydroxyapatite affects the composition, structure, and mechanical properties of human cortical bone. AB - Strontium ranelate and fluoride salts are therapeutic options to reduce fracture risk in osteoporosis. Incorporation of these elements in the physiological hydroxyapatite matrix of bone is accompanied by changes in bone remodeling, composition, and structure. However, a direct comparison of the effectiveness of strontium and fluoride treatment in human cortical bone with a focus on the resulting mechanical properties remains to be established. Study groups are composed of undecalcified specimens from healthy controls, treatment-naive osteoporosis cases, and strontium ranelate or fluoride-treated osteoporosis cases. Concentrations of both elements were determined using instrumental neutron activation analysis (INAA). Backscattered electron imaging was carried out to investigate the calcium content and the cortical microstructure. In comparison to osteoporotic patients, fluoride and strontium-treated patients have a lower cortical porosity indicating an improvement in bone microstructure. Mechanical properties were assessed via reference point indentation as a measure of bone's resistance to deformation. The strontium-incorporation led to significantly lower total indentation distance values compared to osteoporotic cases; controls have the highest resistance to indentation. In conclusion, osteoporosis treatment with strontium and fluoride showed positive effects on the microstructure and the mechanical characteristics of bone in comparison to treatment-naive osteoporotic bone. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 433-442, 2017. PMID- 27684388 TI - Healthcare-seeking behaviour in relation to sexual and reproductive health among Thai-born women in Sweden: a qualitative study. AB - Thailand is one of the most common countries of origin among immigrants in Sweden and Thai immigrants comprise the immigrant group most frequently diagnosed with HIV. Little is known about their healthcare-seeking behaviour and views on HIV prevention. This study explored Thai women's healthcare-seeking behaviour in relation to sexual and reproductive health and their views on HIV prevention. Nineteen in-depth interviews were conducted with Thai-born women in the Stockholm area. Three themes were identified: (1) poor access to healthcare in Sweden, preferring to seek care in Thailand; (2) partners playing a key role in women's access to healthcare; (3) no perceived risk of HIV, but a positive attitude towards prevention. Despite expressing sexual and reproductive healthcare needs, most women had not sought this type of care, except for the cervical cancer screening programme to which they had been invited. Identified barriers for poor access to healthcare were lack of knowledge about the healthcare system and language difficulties. To achieve 'healthcare on equal terms', programmes and interventions must meet Thai women's healthcare needs and consider what factors influence their care-seeking behaviour. Integrating HIV prevention and contraceptive counselling into the cervical screening programme might be one way to improve access. PMID- 27684389 TI - Equity and Justice in Developmental Science: Discrimination, Social Exclusion, and Intergroup Attitudes. AB - In this article, the authors assert that (a) the topics of equity and justice reflect important areas of developmental science theory and research which have not yet been recognized as central areas of research in child development and developmental science, (b) a concern for social inequalities serves as a common thread binding equity and justice research across different areas in developmental science, and (c) equity and justice research can inform policies and practices that are designed to improve the lives of all children (including those who are members of stigmatized groups) reduce prejudice and bias, and create programs to rectify social inequalities. For this special section of Child Development, the authors provide the context for this research, and highlight the articles in this special section to demonstrate cutting-edge research in developmental science regarding equity and justice. The authors review current research and make recommendations for new lines of inquiry. PMID- 27684390 TI - Trajectories of Discrimination Across Adolescence: Associations With Academic, Psychological, and Behavioral Outcomes. AB - The authors explored trajectories of perceived discrimination over a 6-year period (five assessments in 6th-11th grade) in relation to academic, behavioral, and psychological adjustment in 8th and 11th grades. They distinguished discrimination from adults versus peers in addition to overt versus covert discrimination from peers. The sample included 226 African American, White, Dominican, Puerto Rican, and Chinese adolescents (ages 11-12 at Time 1) recruited in sixth grade from six public schools in New York City. All forms of discrimination increased during middle school and decreased during high school. The frequency with which adolescents reported different sources and types of discrimination varied across ethnicity/race, but not gender. Initial levels and rates of change in discrimination predicted academic, behavioral, and psychological adjustment in 8th and 11th grades, albeit in complex ways. PMID- 27684391 TI - Minority Adolescents in Ethnically Diverse Schools: Perceptions of Equal Treatment Buffer Threat Effects. AB - Can perceptions of equal treatment buffer the negative effects of threat on the school success of minority students? Focusing on minority adolescents from Turkish and Moroccan heritage in Belgium (Mage = 14.5; N = 735 in 47 ethnically diverse schools), multilevel mediated moderation analyses showed: (a) perceived discrimination at school predicted lower test performance; (b) experimentally manipulated stereotype threat decreased performance (mediated by increased disengagement); (c) perceived equal treatment at school predicted higher performance (mediated by decreased disengagement); and (d) personal and peer perceptions of equal treatment buffered negative effects of discrimination and stereotype threat. Thus, (situational) stereotype threat and perceived discrimination at school both undermine minority student success, whereas perceived equal treatment can provide a buffer against such threats. PMID- 27684392 TI - Neighborhood Characteristics and Expectations of Racially Discriminatory Experiences Among African American Adolescents. AB - This study examined how youth's neighborhood characteristics informed their expectations of racial discrimination concurrently and longitudinally. Secondary analyses were conducted on data from Waves 1, 3, 4, 5, and 6 of the Maryland Adolescent Development in Context Study, which permitted the examination of neighborhood influences among a socioeconomically diverse sample of African American parents and adolescents (n = 863; Mage = 12.29). Youth exposed to more neighborhood disadvantage in seventh grade reported more negative concurrent neighborhood perceptions, which, in turn, predicted greater expectations of racial discrimination in eighth grade; youth's expectations remained stable into adulthood. Thus, support was found for the mediating role of youth's subjective neighborhood perceptions in the longitudinal relation between neighborhood structure and expectations of racial discrimination. PMID- 27684393 TI - Race-Based Humor and Peer Group Dynamics in Adolescence: Bystander Intervention and Social Exclusion. AB - Adolescents' evaluations of discriminatory race-based humor and their expectations about peer responses to discrimination were investigated in 8th- (Mage = 13.80) and 10th-grade (Mage = 16.11) primarily European-American participants (N = 256). Older adolescents judged race-based humor as more acceptable than did younger adolescents and were less likely to expect peer intervention. Participants who rejected discrimination were more likely to reference welfare/rights and prejudice and to anticipate that peers would intervene. Showing awareness of group processes, adolescents who rejected race based humor believed that peers who intervened would be more likely to be excluded. They also disapproved of exclusion more than did participants who supported race-based humor. Results expose the complexity of situations involving subtle discrimination. Implications for bullying interventions are discussed. PMID- 27684394 TI - Perceived Peer and Parent Out-Group Norms, Cultural Identity, and Adolescents' Reasoning About Peer Intergroup Exclusion. AB - Cultural group identity and group norms are significantly related to social exclusion evaluations (Bennett, ). This study examined 241 Jewish-American mid (M = 14.18 years, SD = 0.42) to late (M = 17.21 years, SD = 0.43; MageTOTAL = 15.54 years, SD = 1.57) adolescents' cultural identities and contextually salient perceived group norms in relation to their evaluations of Arab-American inclusion and exclusion across two contexts (peers vs. family at home). Results suggest that perceived group norms are related to the context in which they are applied: parents in the home and peers in the peer context. Peers remained a significant source of perceived group norms in the home context. Significant interactions emerged between perceived parent group norms and cultural identity. Findings highlight the need to address group-specific norms by context to ensure maximum effectiveness for intergroup interventions. PMID- 27684395 TI - Race Essentialism and Social Contextual Differences in Children's Racial Stereotyping. AB - The authors explored the differential emergence and correlates of racial stereotyping in 136 children ages 4-11 years across two broad social contexts: Hawai'i and Massachusetts. Children completed measures assessing race salience, race essentialism, and in-group and out-group stereotyping. Results indicated that the type of racial stereotypes emerging with age was context dependent. In both contexts in-group stereotyping increased with age. In contrast, there was only an age-related increase in out-group stereotyping in Massachusetts. Older children in Massachusetts reported more essentialist thinking (i.e., believing that race cannot change) than their counterparts in Hawai'i, which explained their higher out-group stereotyping. These results provide insight into the factors that may shape contextual differences in racial stereotyping. PMID- 27684396 TI - Development of Expectancies About Own- and Other-Gender Group Interactions and Their School-Related Consequences. AB - This study examined children's expectancies about interactions with own- and other-gender peers. Goals were to examine expectancies about the outcomes related to own- versus other-gender group interactions, assess cohort and temporal changes in expectancies, and assess the effect of expectancies on school-related outcomes. Students in second and fourth grades (N = 412, 47% girls, Mage = 7.15 and 9.10 years, respectively) were followed longitudinally for 1 year. Results supported hypotheses that social costs and inclusion-enjoyment that children expect in interactions with own- and other-gender peers represent four constructs. Expectancies varied by gender, age, and differentially predicted school outcomes with inclusion expectancies more strongly relating to outcomes than cost expectancies. Implications of children's expectancies about gendered contexts are discussed. PMID- 27684397 TI - How School Norms, Peer Norms, and Discrimination Predict Interethnic Experiences Among Ethnic Minority and Majority Youth. AB - This research tests how perceived school and peer norms predict interethnic experiences among ethnic minority and majority youth. With studies in Chile (654 nonindigenous and 244 Mapuche students, M = 11.20 and 11.31 years) and the United States (468 non-Hispanic White and 126 Latino students, M = 11.66 and 11.68 years), cross-sectional results showed that peer norms predicted greater comfort in intergroup contact, interest in cross-ethnic friendships, and higher contact quality, whereas longitudinal results showed that school norms predicted greater interest in cross-ethnic friendships over time. Distinct effects of school and peer norms were also observed for ethnic minority and majority youth in relation to perceived discrimination, suggesting differences in how they experience cross ethnic relations within school environments. PMID- 27684398 TI - Ethnic Attitudes and Social Projection in the Classroom. AB - This research examined the process and conditions of social projection of biased ethnic attitudes to classmates in two samples of Grades 4-6 children (n = 342, Mage = 10.75, SD = 0.98; 49% girls; and n = 525, Mage = 10.49 years, SD = 0.96; 51% girls). Children reported on the ethnic group norm in their classroom and on their own ethnic attitudes. Multilevel analyses showed that ethnic majority (Studies 1 and 2) and ethnic minority (Study 2) children's norm perceptions were partly accurate as they not only reflected the aggregated attitudes in each classroom but also related to children's unique attitudes that indicated social projection. Projection was stronger for the most disadvantaged minority group and for children with less depressed affect. PMID- 27684399 TI - Developmental Dynamics of Intergroup Contact and Intergroup Attitudes: Long-Term Effects in Adolescence and Early Adulthood. AB - Intergroup contact represents a powerful way to improve intergroup attitudes and to overcome prejudice and discrimination. However, long-term effects of intergroup contact that consider social network dynamics have rarely been studied at a young age. Study 1 validated an optimized social network approach to investigate intergroup contact (N = 6,457; Mage = 14.91 years). Study 2 explored the developmental trajectories of intergroup contact by applying this validated network approach in a cross-sequential design (four-cohort-four-wave; N = 3,815; 13-26 years). Accelerated growth curve models showed that contact predicts the development of attitudes in adolescence, whereas acquired attitudes buffer against decreasing contact in adulthood. Findings highlight the potential of social network analysis and the developmental importance of early intergroup contact experiences. PMID- 27684402 TI - Corrigendum: Correction to Supporting Information. PMID- 27684400 TI - Growing Up Amid Ethno-Political Conflict: Aggression and Emotional Desensitization Promote Hostility to Ethnic Outgroups. AB - Ethno-political violence impacts thousands of youth and is associated with numerous negative outcomes. Yet little research examines adaptation to ethno political violence over time or across multiple outcomes simultaneously. This study examines longitudinal patterns of aggressive behavior and emotional distress as they co-occur among Palestinian (n = 600) youth exposed to ethno political violence over 3 years in three age cohorts (starting ages: 8, 11, and 14). Findings indicate distinct profiles of aggressive behavior and emotional distress, and unique joint patterns. Furthermore, youth among key joint profiles (e.g., high aggression-emotional desensitization) are more likely to endorse normative beliefs about aggression toward ethnic outgroups. This study offers a dynamic perspective on emotional and behavioral adaptation to ethno-political violence and the implications of those processes. PMID- 27684401 TI - Commentary: The Role of Race/Ethnicity in a Developmental Science of Equity and Justice. AB - This commentary makes a case for the role of school racial/ethnic diversity in a new developmental science of equity and justice with a focus on intergroup attitudes, discrimination, and social exclusion. Creative ways to conceptualize and measure ethnic diversity as a multifaceted, dynamic, and fluid construct that changes across time and space are discussed. The commentary concludes with policy implications of this approach for improving the lives of children growing up in an increasingly multiracial/multiethnic society. PMID- 27684403 TI - Modulation of MMP-2 and MMP-9 through connected pathways and growth factors is critical for extracellular matrix balance of intra-articular ligaments. AB - The healing mechanism of cruciate ligaments is not well elucidated. Crosstalk between adjacent tissues in the knee joint plays an important role in wound healing and tissue regeneration, but the gelatinase modulation in posterior cruciate ligament fibroblasts (PCLfs) and synovial cells (SCs) based on co culture is still elusive. The present study sought to systematically elucidate the gelatinase modulation in both PCLfs and SCs based on in vitro co-culture and in a rabbit PCL-injury model in vivo. It was found that injured PCLfs and SCs can secrete high gelatinases after co-culture. Cytokines promote greater gelatinase secretion by both injured PCLfs and SCs in the form of monomers and dimers. Pathway inhibitors can reduce injury-induced gelatinase activities, but the presence of cytokines restores the higher activity. Inhibitor cocktails can reduce gelatinase expression to a normal level even in the presence of cytokines. Growth factors promote wound healing of the injured PCL by enhancing cell migration, proliferation and collagen synthesis, but also upregulate gelatinases. Modified inhibitor cocktails containing growth factor can also reduce gelatinase expression to a normal level. This gelatinase modulation was also verified in a rabbit PCL injury model in vivo. Together, the results aids understanding of the mechanism of gelatinase modulation in injured PCL ligament post-crosstalk with synovium and infers that the gelatinases could be a potential as a therapeutic target for acute ligament injury. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27684404 TI - Bullous drug eruption to Nigella sativa oil: Consideration of the use of a herbal medicine - clinical report and review of the literature. PMID- 27684405 TI - Internet-Based Psychotherapy for Adult Depression: What About the Mechanisms of Change? AB - INTRODUCTION: Internet-based cognitive behavioral therapy for depression (iCBT) has been advanced as a valuable alternative treatment option, generating promising results. However, little is known about its underlying mechanisms of change. OBJECTIVE: We aimed to provide an overview of the state of the art regarding the mechanisms of iCBT for adult depression, in the context of iCBT efficacy. METHOD: We conducted a systematic qualitative review of 37 randomized clinical trials, assessed the risk of bias in the included studies, and used a systematic evaluative framework to establish the scientific status of iCBT, based on evidence regarding clinical efficacy and mechanisms of change. RESULTS: Findings indicated that iCBT mechanisms of change are clearly underinvestigated, although iCBT is relatively efficacious, at least in the short term. The quality of iCBT randomized clinical trials proved to be suboptimal. CONCLUSIONS: The iCBT theory should be clearly specified and adequately investigated to design and implement highly efficacious therapeutic packages. Without considering the iCBT mechanisms of change along with iCBT efficacy, the extent to which iCBT is an empirically validated treatment remains questionable. PMID- 27684407 TI - Conservative Management of Unilateral Fractures of the Mandibular Rami in Horses. AB - OBJECTIVE: To report the outcome of conservative management of unilateral fractures of the mandibular rami in horses. STUDY DESIGN: Retrospective case series. ANIMALS: 24 client-owned horses with unilateral mandibular fractures METHODS: Medical records (January 2000-January 2014) of horses with unilateral mandibular ramus fractures were retrieved. Only conservatively managed horses with follow-up information were included. Follow-up information on clinical outcome was retrieved from the medical records (n=11) or obtained by telephone interviews with the owners or trainers (n=13). RESULTS: Twenty-three horses (96%) returned to their previous or intended use and had no clinically evident masticatory or fracture healing-related problems at the time of follow-up. The owner of 1 horse (4%) reported it had tooth loosening, feed impaction, and masticatory problems. CONCLUSION: Conservative management of unilateral fractures of the mandibular rami is a treatment option in horses. PMID- 27684406 TI - Altered whole-brain connectivity in albinism. AB - Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27684408 TI - The profession of neuropsychology in Spain: results of a national survey. AB - OBJECTIVE: To examine the current status of professional neuropsychology in Spain, with particular focus on the areas of professional training, current work situation, evaluation and diagnostic practice, rehabilitation, teaching, and research. METHODS: Three hundred and thirty-nine self-identified professionals in neuropsychology from Spain completed an online survey between July and December of 2013. Respondents had an average age of 35.8 years and 77% were women. RESULTS: Ninety-seven percent of the respondents identified as psychologists; 82% of the sample had a master's degree, and 33% a doctoral degree. The majority (91%) received their neuropsychological training at a graduate level; 88% engaged in neuropsychological evaluation, 59% in rehabilitation, 50% in research, and 40% in teaching. Average number of hours per week dedicated to work in neuropsychology was 29.7, with 28% of the respondents reporting working in hospitals, 17% in not-for-profit rehabilitation centers, 15% in universities, and 14% in private clinics. Clinicians primarily work with individuals with stroke, traumatic brain injury, and dementia. The top perceived barriers to development of neuropsychology in Spain included lack of clinical and academic training opportunities, and negative attitude toward professional collaboration. CONCLUSIONS: The field of neuropsychology in Spain is young and rapidly growing. There is a need to regulate professional neuropsychology, improve graduate curricula, enhance existing clinical training, develop professional certification programs, validate and create normative data for existing neuropsychological tests, and create new, culturally relevant instruments. PMID- 27684409 TI - Pre-transplant bone marrow myeloma cells: less is better. PMID- 27684410 TI - Corrigendum. PMID- 27684411 TI - Oncogenic Actions of SKP2 Involves Deregulation of CDK1 Turnover Mediated by FOXM1. AB - Cyclin-dependent kinases (cdks) are central catalytic units of cell division cycle. Among the cdk family members, cdk1 has critical roles in multiple phases of the cell cycle. Aberrant expression or hyper-actions of cdk1 are tumorigenic and yet the complex oncogenic network that regulates its turnover is poorly understood. We found a hitherto unexplored functional connection between skp2 and cdk1 turn over. In vitro knockdown or overexpression of skp2 in cultured cells reduced or induced cdk1 expression indicating skp2 as a positive driver for cdk1. A partial inhibitory role for p27 was identified in this context. Interestingly, concurrent overexpression of skp2 and p27 favored cdk1 upregulation in vitro, which correlated well with similar observations in clinical tumor samples. We found that the transcription factor FOXM1 may play a central role in the skp2 cdk1 loop. Additional molecular involvement in the skp2-cdk1 loop was also explored. In conclusion, our results revealed hitherto unexplored p27 independent molecular mechanisms for skp2 driven tumor progression. Our results support the previous findings that skp2 may be a potential therapeutic target for the management of tumors. J. Cell. Biochem. 118: 797-807, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27684412 TI - Lipid effects of switching from prescription EPA+DHA (omega-3-acid ethyl esters) to prescription EPA only (icosapent ethyl) in dyslipidemic patients. AB - OBJECTIVES: Residual cardiovascular risk and persistently elevated triglycerides (TGs) may remain despite statin therapy in patients with dyslipidemia. Prescription omega-3 fatty acid formulations containing docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) have been shown to reduce TGs and may potentially lower residual cardiovascular risk. However, DHA may raise low density lipoprotein cholesterol (LDL-C) and compromise treatment goals. Icosapent ethyl (Vascepa(r)), a high-purity prescription EPA formulation, has been shown to lower TGs and other lipid parameters without raising LDL-C. There are no prospective, randomized, controlled trials of the effects of switching patients from omega-3-acid ethyl esters (Lovaza(r)), a prescription formulation containing EPA+DHA, to icosapent ethyl. METHODS: This retrospective chart review included records of high-risk patients aged >=18 years receiving stable statin therapy for dyslipidemia who had been switched from prescription omega-3-acid ethyl esters 4 g/day to prescription icosapent ethyl 4 g/day and had available laboratory lipid profiles after receiving each for >=2 months. Lipid assessments were conducted by local laboratories. Patient records were excluded if there were changes in medication or health condition that could affect lipid parameters. RESULTS: The records of 8 patients (6 women and 2 men; 54-83 years) met eligibility criteria. Following the switch to icosapent ethyl, LDL-C changes ranged from +3.2% to 69.1% (reduced in 7 patients), total cholesterol was reduced in all patients ( 3.5% to -44.3%), and TG changes ranged from +32.4% to -59.0% (reduced in 6 patients). Decreases or no changes in non-high-density lipoprotein cholesterol were observed; changes in high-density lipoprotein cholesterol varied. No adverse events related to either product were reported. CONCLUSION: In this real-world retrospective analysis, switching high-risk statin-treated patients from omega-3 acid ethyl esters to icosapent ethyl resulted in favorable lipid changes. The analysis was limited by the small patient numbers, but lipid results were consistent with randomized controlled trials and previous case series. PMID- 27684414 TI - Prognostic accuracy of antenatal neonatology consultation. AB - OBJECTIVE: Neonatologists provide antenatal counseling to support shared decision making for complicated pregnancies. Poor or ambiguous prognostication can lead to inappropriate treatment and parental distress. We sought to evaluate the accuracy of antenatal prognosticaltion. STUDY DESIGN: A retrospective cohort was assembled from a prospectively populated database of all outpatient neonatology consultations. On the basis of the written consultation, fetuses were characterized by diagnosis groups (multiple anomalies or genetic disorders, single major anomaly and obstetric complications), assigned to five prognostic categories (I=survivable, IIA=uncertain but likely survivable, II=uncertain, IIB=uncertain but likely non-survivable, III non-survivable) and two final outcome categories (fetal demise/in-hospital neonatal death or survival to hospital discharge). When possible, status at last follow-up was recorded for those discharged from the hospital. Prognostic accuracy was assessed using unweighted, multi-level likelihood ratios (LRs). RESULTS: The final cohort included 143 fetuses/infants distributed nearly evenly among the three diagnosis groups. Over half (64%) were assigned an uncertain prognosis, but most of these could be divided into 'likely survivable' or 'likely non-survivable' subgroups. Overall survival for the entire cohort was 62% (89/143). All but one of the fetuses assigned a non-survivable prognosis suffered fetal demise or died before hospital discharge. The neonatologist's antenatal prognosis accurately predicted the probability of survival by prognosis group (LR I=4.56, LR IIA=10.53, LR II=4.71, LR IIB=0.099, LR III=0.040). The LRs clearly differentiated between fetuses with high and low probability of survival. Eleven fetuses (7.7%) had misalignment between the predicted prognosis and outcome. Five died before discharge despite being given category I or IIA prognoses, whereas six infants with category IIB or III prognoses survived to discharge, though some of these were discharged to hospice care. CONCLUSIONS: The neonatologist's antenatal prognosis accurately predicted fetal-neonatal outcome. Infants with non survivable or uncertain but likely poor prognoses had a very low probability of survival, whereas those with good or uncertain prognoses had a high probability of survival. There were few cases of prognostic failure with most occurring in fetuses with one major or multiple anomalies. The few cases of prognostic failure suggest a need for caution. Honest disclosure of prognostic uncertainty and shared decision-making with families utilizing their personal values is critical in the antenatal encounter. PMID- 27684413 TI - Characteristics of neonatal transports in California. AB - OBJECTIVE: To describe the current scope of neonatal inter-facility transports. STUDY DESIGN: California databases were used to characterize infants transported in the first week after birth from 2009 to 2012. RESULTS: Transport of the 22 550 neonates was classified as emergent 9383 (41.6%), urgent 8844 (39.2%), scheduled 2082 (9.2%) and other 85 (0.4%). In addition, 2152 (9.5%) were initiated for delivery attendance. Most transports originated from hospitals without a neonatal intensive care unit (68%), with the majority transferred to regional centers (66%). Compared with those born and cared for at the birth hospital, the odds of being transported were higher if the patient's mother was Hispanic, <20 years old, or had a previous C-section. An Apgar score <3 at 10 min of age, cardiac compressions in the delivery room, or major birth defect were also risk factors for neonatal transport. CONCLUSION: As many neonates receive transport within the first week after birth, there may be opportunities for quality improvement activities in this area. PMID- 27684415 TI - Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure (BP-CPAP) following CPAP failure in infants <1250 g: a pilot randomized controlled trial. AB - OBJECTIVE: Non-invasive high-frequency ventilation (NIHFV), a relatively new modality, is gaining popularity despite limited data. We sought to evaluate the effectiveness of NIHFV versus bi-phasic continuous positive airway pressure (BP CPAP) in preterm infants failing CPAP. STUDY DESIGN: Infants with BW<1250 g on CPAP were randomly assigned to NIHFV or BP-CPAP if they met pre-determined criteria for CPAP failure. Infants were eligible for randomization after 72 h age and until 2000 g. Guidelines for adjustment of settings and criteria for failure of assigned mode were implemented. The primary aim was to assess feasibility of a larger trial. In addition, failure of assigned non-invasive respiratory support (NRS) mode, invasive mechanical ventilation (MV) 72 h and 7 days post randomization, and bronchopulmonary dysplasia (BPD) were assessed. RESULTS: Thirty-nine infants were randomized to NIHFV (N=16) or BP-CPAP (N=23). There were no significant differences in mean (s.d.) postmenstrual age (28.6 (1.5) versus 29.0 (2.3) weeks, P=0.47), mean (s.d.) weight at randomization (965.0 (227.0) versus 958.1 (310.4) g, P=0.94) or other baseline demographics between the groups. Failure of assigned NRS mode was lower with NIHFV (37.5 versus 65.2%, P=0.09), although not statistically significant. There were no differences in rates of invasive MV 72 h and 7 days post-randomization or BPD. CONCLUSION: NIHFV was not superior to BP-CPAP in this pilot study. Effectiveness of NIHFV needs to be proven in larger multi-center, appropriately powered trials before widespread implementation. PMID- 27684416 TI - Analysis of circulating human and viral microRNAs in patients with congenital cytomegalovirus infection. AB - OBJECTIVE: Cytomegalovirus (CMV) is the most common cause of congenital infection and can cause neurodevelopmental disabilities, although a majority of patients are asymptomatic. Biomarkers associated with disease severity would be desirable to distinguish asymptomatic from mildly symptomatic patients who may benefit from antiviral treatment. MicroRNAs (miRNAs) are noncoding RNAs that may have the potential to serve as biomarkers. STUDY DESIGN: Thirteen infants with congenital CMV infection were enrolled, and plasma levels of 11 human- and 3 CMV-encoded miRNAs were quantitated by real-time PCR. Plasma levels of miRNAs and their associations with clinical features were evaluated. RESULTS: The levels of miR 183-5p and miR-210-3p were significantly higher in patients with congenital CMV infection than in control infants, whereas no significant associations between levels of miRNAs and clinical features of congenital CMV infection were observed. CONCLUSION: Plasma miRNAs could be associated with the pathogenesis of congenital CMV infection and could be used as disease biomarkers. PMID- 27684417 TI - Identification of bacterial invasion in necrotizing enterocolitis specimens using fluorescent in situ hybridization. AB - OBJECTIVE: Investigation of bacterial invasion into the intestinal wall in necrotizing enterocolitis (NEC) specimens. STUDY DESIGN: We compared 43 surgical NEC specimens with 43 age-matched controls. We used fluorescent in situ hybridization (FISH), a universal bacterial probe together with species-specific probes for Clostridium spp., Enterobacteriaceae, bacteroides and enterococci/lactobacilli. We used a FISH scoring system to reveal invasion of the intestinal wall, in which 1 represented no colonies and 4 invasion of the intestinal wall. RESULTS: We observed invasion of the intestinal wall in 22/43 of the most affected NEC tissue samples as compared with 16/43 in the least affected NEC tissue samples (P=0.03). A FISH score of 4 was reached in 7/43 control cases. Enterobacteriaceae dominated the NEC specimens. Clostridium spp. were detected occasionally in NEC samples. CONCLUSION: Bacterial invasion of the intestinal wall is more present in most affected NEC tissue samples compared with least affected NEC tissue samples or controls. Enterobacteriaceae are prevalent in advanced NEC. PMID- 27684418 TI - Improving fortification with weekly analysis of human milk for VLBW infants. AB - OBJECTIVE: To track individual mother's macronutrient variability in preterm human milk (HM) over 6 weeks of lactation. STUDY DESIGN: This was a prospective, observational study of mother's own milk from women who delivered a very low birth weight infant (<1500 g). A single, random maternal breast milk sample was collected and analyzed weekly for 6 consecutive weeks. Analysis was by mid infrared spectroscopy. RESULTS: Twenty women consented to provide at least one milk sample. Fat, protein and energy content varied widely among mothers and by week of lactation. Energy content ranged from 9.5 to 30.4 kcal oz-1 across the study period. Twenty-five percent of all samples had an energy content <17 kcal oz-1. Protein content ranged from 1.1 to 2.8 g dl-1 in the first week. Sixty three percent of all samples had a protein content <1.5 g dl-1. Fat and energy showed trends of increasing concentrations, whereas protein showed the expected decline over time. Lactose showed little variability by woman or by week of lactation. CONCLUSION: HM fat and protein content varied widely by individual woman over time. Week-to-week variability in fat and protein can impact growth. The ability to analyze HM is helpful to improve fortification of HM. PMID- 27684419 TI - Prospective economic evaluation alongside the non-invasive ventilation trial. AB - OBJECTIVE: To determine the cost-effectiveness of nasal continuous positive pressure (nCPAP) compared with nasal intermittent positive pressure ventilation (NIPPV) in the context of the reported randomized clinical trial. STUDY DESIGN: Using patient-level data from the clinical trial, we undertook a prospectively planned economic evaluation. We measured costs, from a third-party payer perspective in all patients, and from a societal perspective in a subgroup with a time horizon through the earlier of discharge, death or 44 weeks post-menstrual age. RESULTS: From the third-party payer perspective, the mean cost of hospitalization per infant was statistically similar, $143 745 in the NIPPV group compared to $140 403 in the nCPAP group. Cost-effectiveness evaluation revealed a 61% probability that NIPPV is more expensive and less effective than nCPAP. Similar results were found in subgroup analysis from a societal perspective. CONCLUSION: In addition to being clinically equivalent, economic evaluation confirms that NIPPV, as employed in this trial, is also not economically favorable. PMID- 27684420 TI - Sexual partner testing for HIV to eliminate mother-to-child HIV transmission: a needs assessment in an urban hospital community clinic. AB - OBJECTIVE: To characterize pregnant patients' knowledge, attitudes and preferences regarding antenatal HIV testing for themselves and their sexual partners. STUDY DESIGN: Observational, mixed methods study of HIV-negative pregnant women from a university-based urban clinic. Participants completed an anonymous survey about HIV testing for themselves and their partners. Descriptive statistics, bivariable analyses, multivariable logistic regression and qualitative thematic analysis were utilized. RESULTS: One hundred and forty-two patients (mean age 28.6+/-5.5 years) participated. A majority (57.7%) were married or partnered, and 92.9% reported having at least one current sexual partner. Although a majority (62.8%) reported their partner had a prior HIV test, and 93.0% of these women were aware of test results, only 20.7% reported partner testing had occurred in the past 6 months. Women who had a prior HIV test, who were older or who were non-white were more likely to be aware of their partner's HIV status. A majority (66.9%) of women desired knowledge of their partner's current status and 76.0% believed their partners would like to know his HIV status; in addition, 74% were interested in receiving partner testing at the site of prenatal care. Qualitative analysis demonstrated that health concerns and believing HIV knowledge is important to the relationship were motivators for desiring partner testing. CONCLUSIONS: In this urban community, a majority of pregnant women do not know HIV test results of their sexual partner during the current pregnancy. Women desired to know their partner's HIV status and were receptive to partner testing at the site of prenatal care or other locations. Partner testing may be a critical step toward elimination of seroconversion during pregnancy and maternal-to-child HIV transmission. PMID- 27684421 TI - Clinically significant cardiopulmonary events and the effect of definition standardization on apnea of prematurity management. AB - OBJECTIVE: To define the impact of care standardization on caffeine and cardiorespiratory monitoring at neonatal intensive care unit (NICU) discharge. STUDY DESIGN: Electronic records were abstracted for infants aged 24-36 weeks gestation with birth weights appropriate for gestational age. Infants who died, transferred prior to discharge, had major pulmonary anomalies, required a home monitor for mechanical ventilation or had a family history of sudden infant death syndrome were excluded. Data and records were used to indicate when the new definition of clinically significant cardiopulmonary events (CSCPEs) and concurrent education was implemented. Preimplementation and postimplementation cohorts were compared. RESULTS: Incidence fell from 74% diagnosed with apnea of prematurity at baseline to 49% diagnosed with CSCPE postimplementation (P<0.001). Infants discharged on caffeine reduced from 17% to 5% (P<0.001), and home monitor use also fell from 54% to 16% (P<0.001). CONCLUSION: Standardizing definitions and treatments reduced the use of caffeine and cardiorespiratory monitors upon NICU dismissal. PMID- 27684422 TI - Preparedness of pediatric residents for fellowship: a survey of US neonatal perinatal fellowship program directors. AB - OBJECTIVE: To evaluate the preparedness of pediatric residents entering accredited neonatal-perinatal medicine (NPM) fellowships in the United States. STUDY DESIGN: A multi-domain, validated survey was distributed to Program Directors (PDs) of US NPM fellowship programs. The 47-item survey explored 5 domains: professionalism, independent practice, psychomotor ability, clinical evaluation, and academia. A systematic, qualitative analysis on free-text comments was also performed. RESULTS: Sixty-one PDs completed the survey, for a response rate of 62% (61/98). For entering fellows, PDs assessed performance in professionalism positively, including 76% as communicating effectively with parents and 90% treating residents/house-staff with respect. In contrast, most PDs rated performance in psychomotor abilities negatively, including 59% and 79% as deficient in bag-and-mask ventilation and neonatal endotracheal intubation, respectively. Although 62% of PDs assessed entering fellows positively for genuine interest in academic projects, fewer than 10% responded positively that entering fellows understood research protocol design, basic statistics, or were capable of writing a cohesive manuscript well. Thematic clustering of qualitative data revealed deficits in psychomotor ability and academia/scholarship. CONCLUSIONS: On the basis of the perspective of front line educators, graduating pediatric residents are underprepared for subspecialty fellowship training in NPM. To provide the best preparation for pediatric graduates who pursue advanced training, changes to residency education to address deficiencies in these important competencies are warranted. PMID- 27684423 TI - Do serum and urinary concentrations of kidney injury molecule-1 in healthy newborns depend on birth weight, gestational age or gender? AB - OBJECTIVE: The aim of work was to establish the normal levels of serum and urinary kidney injury molecule-1 (sKIM-1 and uKIM-1) in healthy full-term newborns. STUDY DESIGN: The study included 88 healthy full-term neonates from normal, uncomplicated pregnancies. The serum and urinary concentrations of KIM-1 in the material obtained in the first or second day of life were determined with a commercially available enzyme-linked immunosorbent assay kits. In addition, uKIM-1 was normalized for urinary creatinine concentration. RESULTS: Male and female newborns, as well as children in whom the samples were obtained in the first or second day of life, did not differ significantly in terms of their sKIM 1 and uKIM-1 levels. Gestational age correlated inversely with sKIM-1 and positively with uKIM-1, but not with uKIM-1/cr. No correlation was found with birth weight and gender. CONCLUSION: This is the first report of sKIM-1 and uKIM 1 levels in healthy full-term newborns during the first postnatal days. The data from healthy newborns may serve as the reference values for future studies in the youngest children. PMID- 27684424 TI - Photoplethysmographic waveform characteristics of newborns with coarctation of the aorta. AB - OBJECTIVE: Fetal echocardiography, physical examination and pulse oximetry detect only half of coarctation of aorta (CoA) cases. We aimed to quantify delayed arrival and diminished amplitude of lower extremity photoplethysmographic (PPG) pulses relative to the right hand in affected patients. STUDY DESIGN: We studied 8 CoA infants and 32 healthy controls. The pulse arrival time difference between foot and hand (f-hTD) and pulse amplitude ratio (F/H) were measured on PPG signal waveforms by digitally-determining maxima and minima of systolic decrease of light transmission. Mann-Whitney test was used for group comparisons. RESULTS: In comparison to healthy newborns, CoA infants' PPG waveforms demonstrated prolonged f-hTD (mean+/-s.d. of 73.2+/-26.6 versus 35.2+/-8.3 ms, P<0.001) and lower F/H (0.57+/-0.26 versus 0.99+/-0.58, P=0.014). CONCLUSIONS: F-hTD and F/H are quantifiable from hand- and foot-derived PPG waveforms and are significantly different in CoA versus healthy newborns. Larger studies are needed to validate PPG for improved critical congenital heart disease screening. PMID- 27684427 TI - Prolonged impairment of deglutition in supratentorial ischaemic stroke: the predictive value of Parramatta Hospitals' Assessment of Dysphagia. AB - BACKGROUND: Up to 50% of ischaemic stroke patients show initial dysphagia, which may persist for months. Guidelines recommend switching nasogastric (NG) to percutaneous endoscopic gastrostomy (PEG) tube feeding at the second week after the stroke if impaired deglutition is expected for another 4 weeks. Precise prognostic criteria are lacking. We hypothesised that the Parramatta Hospitals' Assessment of Dysphagia (PAHD) performed 8 to 10 days after the stroke predicts impaired deglutition for another 4 weeks. METHODS: After a first dysphagia assessment (buccolingual motor function, liquid and semisolid swallow tests, "two out-of-six" scale) within 48 hours of onset, patients with a first hemispheric stroke and risk of aspiration, defined as a two-out-of-six scale score of >=2 (dysphonia, dysarthria, abnormal gag reflex, abnormal volitional cough, cough / voice change after swallowing) were included and were assessed by a blinded rater using the PHAD. The same dysphagia assessments were repeated 8 to 10 days after the stroke (second assessment) and patients remained in the study if the two-out of-six scale score remained >=2. At a final evaluation by telephone after 4 weeks, impaired deglutition was assessed with the Bogenhausen dysphagia score (BODS-2). Exclusion criteria were infratentorial or recurrent stroke and pre existing dysphagia. The primary objective was to define a threshold score and value of the PHAD at second assessment that predicted impaired deglutition as assessed with the BODS-2 (score >=4) at the final evaluation. The secondary objective was to explore the value of the PHAD assessed within 48 hours to predict impaired deglutition (BODS-2 >=4) at final evaluation. To evaluate the predictive value of the PHAD score assessed 8 to 10 days after stroke onset for impaired deglutition for another 4 weeks, we determined the area under the receiver operating curve (ROC AUC). RESULTS: Over a 1-year period, 29 out of 252 assessed patients remained at risk of aspiration after the second assessment. In these patients, ROC analysis of PHAD recorded 8 to 10 days after the stroke showed excellent accuracy with an AUC of 0.971 (cut-off 71.5) predicting a BODS-2 score of >=4 at final evaluation. The accuracy of ROC analysis of the PHAD score assessed within 48 hours of stroke onset to predict prolonged impairment of deglutition was poor (AUC 0.685). CONCLUSIONS: In a selected population at risk of aspiration, the PHAD with a threshold of 70 assessed in the second week after stroke onset may be a valuable tool to predict prolonged impairment of deglutition for another 4 weeks and to guide the decision about switching from NG to PEG tube feeding after supratentorial ischaemic stroke. PMID- 27684425 TI - Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieu. AB - OBJECTIVE: Oral colostrum priming (OCP) after birth in preterm infants is associated with improved weight gain and modification of the oral immunomicrobial environment. We hypothesized that OCP would modify salivary immune peptides and the oral microbiota in preterm infants. STUDY DESIGN: We conducted a prospective, randomized clinical trial to determine the effects of OCP on salivary immune peptide representation in preterm infants (<32 weeks completed gestation at birth). Saliva samples were collected before and after OCP. Salivary immune peptide representation was determined via mass spectroscopy. Oral microbiota representation was determined via sequencing of the 16S rRNA gene. RESULTS: Neonates who received OCP (n=48) had a 16-day reduction in the median length of hospitalization as compared with infants who did not receive OCP (n=51). No differences in salivary immune peptide sequence representation before OCP between groups were found. Longitudinal changes in peptides were detected (lysozyme C, immunoglobulin A, lactoferrin) but were limited to a single peptide difference (alpha-defensin 1) between primed and unprimed infants after OCP. We found no difference in microbial diversity between treatment groups at any time point, but diversity decreased significantly over time in both groups. OCP treatment marginally modified oral taxa with a decline in abundance of Streptococci in the OCP group at 30 days of life. CONCLUSIONS: OCP had neither an effect on the salivary peptides we examined nor on overall oral bacterial diversity and composition. Infants who received OCP had a reduced length of hospitalization and warrants further investigation. PMID- 27684426 TI - Opportunities for maternal transport for delivery of very low birth weight infants. AB - OBJECTIVE: To assess frequency of very low birth weight (VLBW) births at non level III hospitals. STUDY DESIGN: Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models. RESULTS: Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively. CONCLUSION: Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients. PMID- 27684428 TI - An Acute Retinal Model for Evaluating Blood Retinal Barrier Breach and Potential Drugs for Treatment. AB - A low-cost, easy-to-use and powerful model system is established to evaluate potential treatments that could ameliorate blood retinal barrier breach. An inflammatory factor, histamine, is demonstrated to compromise vessel integrity in the cultured retina through positive staining of IgG outside of the blood vessels. The effects of histamine itself and those of candidate drugs for potential treatments, such as lipoxin A4, are assessed using three parameters: blood vessel leakage via IgG immunostaining, activation of Muller cells via GFAP staining and change in neuronal dendrites through staining for MAP2. Furthermore, the layered organization of the retina allows a detailed analysis of the processes of Muller and ganglion cells, such as changes in width and continuity. While the data presented is with swine retinal culture, the system is applicable to multiple species. Thus, the model provides a reliable tool to investigate the early effects of compromised retinal vessel integrity on different cell types and also to evaluate potential drug candidates for treatment. PMID- 27684431 TI - Different Conformations of 2'-Deoxycytidine in the Gas and Solid Phases: Competition between Intra- and Intermolecular Hydrogen Bonds. AB - Computational results have been reported for 2'-deoxycytidine (dC), its gas phase isomers, tautomers, and their conformers, as well as for the crystalline phase. In addition to the neutral gas phase molecules, we have also considered associated radical anions and cations. The structural calculations were performed at the density functional and MP2 levels of theory. Vertical electron ionization energies and excess electron binding energies were determined using electron propagator theory. The alpha-anomer proved to be more stable by a fraction of kcal/mol than the biologically relevant canonical beta-anomer. The conformational space of canonical dC has been systematically probed. dC in the crystalline phase or DNA structures favors canonical anti conformations. These structures were used in past computational studies to model gas phase characteristics of dC. Our findings indicate, however, that the gas phase dC favors syn conformations. It has repercussions for earlier interpretations of gas phase experimental results based on these computational results. The thermodynamic dominance of syn conformations results from the formation of an intramolecular O5'-H13...O2 hydrogen bond. The IR spectra of the most stable syn and anti canonical conformers differ markedly in the region of frequencies corresponding to NH/OH stretching modes. The MP2 value of deprotonation enthalpy of dC of 1411.7 kJ/mol is in very good agreement with the experimental value of 1409 +/- 2.5 kJ/mol. The most stable valence anions are characterized by electron vertical detachment energies (VDE) in the 0.8-1.0 eV range, in good agreement with the experimental VDE of 0.87 eV. The barrier for the glycosidic bond cleavage is significant in the neutral canonical dC, 40.0 kcal/mol, and it is reduced to 22 and 16 kcal/mol for the anionic and cationic radicals of dC, respectively. The cleavage reaction is exothermic by 4 kcal/mol for dC- and endothermic by 7 and 9 kcal/mol for dC+ and dC, respectively. We decomposed the crystal cohesive energy into repulsive one-body terms associated with the syn-anti conformational changes, and the attractive intermolecular interaction term. We exposed that the syn-anti conformational changes are very favorable for intermolecular interactions; in particular they make the imino-amino side of the cytosine residue accessible to intermolecular interactions. PMID- 27684430 TI - Experimental Protocol to Investigate Particle Aerosolization of a Product Under Abrasion and Under Environmental Weathering. AB - The present article presents an experimental protocol to investigate particle aerosolization of a product under abrasion and under environmental weathering, which is a fundamental element to the approach of nanosafety-by-design of nanostructured products for their durable development. This approach is basically a preemptive one in which the focus is put on minimizing the emission of engineered nanomaterials' aerosols during the usage phase of the product's life cycle. This can be attained by altering its material properties during its design phase without compromising with any of its added benefits. In this article, an experimental protocol is presented to investigate the nanosafety-by-design of three commercial nanostructured products with respect to their mechanical solicitation and environmental weathering. The means chosen for applying the mechanical solicitation is an abrasion process and for the environmental weathering, it is an accelerated UV exposure in the presence of humidity and heat. The eventual emission of engineered nanomaterials is studied in terms of their number concentration, size distribution, morphology and chemical composition. The purpose of the protocol is to study the emission for test samples and experimental conditions which are corresponding to real life situations. It was found that the application of the mechanical stresses alone emits the engineered nanomaterials' aerosols in which the engineered nanomaterial is always embedded inside the product matrix, thus, a representative product element. In such a case, the emitted aerosols comprise of both nanoparticles as well as microparticles. But if the mechanical stresses are coupled with the environmental weathering, the experimental protocol reveals then the eventual deterioration of the product, after a certain weathering duration, may lead to the emission of the free engineered nanomaterial aerosols too. PMID- 27684432 TI - Multicomponent Coupling Reactions of Two N-Tosyl Hydrazones and Elemental Sulfur: Selective Denitrogenation Pathway toward Unsymmetric 2,5-Disubstituted 1,3,4 Thiadiazoles. AB - A copper-mediated, three-component reaction between two different N-Ts hydrazones and elemental sulfur was developed, leading to a series of unsymmetric 2,5 disubstituted 1,3,4-thiadiazoles in moderate yields with good functional group compatibility. This procedure features the employment of elemental sulfur and the selective denitrogenation between aryl and alkyl aldehyde N-tosyl hydrazones, allowing rapid access to unsymmetric 2,5-disubstituted 1,3,4-thiadiazoles frameworks with chemical diversity and complexity. PMID- 27684429 TI - Respiratory Effects of Indoor Heat and the Interaction with Air Pollution in Chronic Obstructive Pulmonary Disease. AB - RATIONALE: There is limited evidence of the effect of exposure to heat on chronic obstructive pulmonary disease (COPD) morbidity, and the interactive effect between indoor heat and air pollution has not been established. OBJECTIVES: To determine the effect of indoor and outdoor heat exposure on COPD morbidity and to determine whether air pollution concentrations modify the effect of temperature. METHODS: Sixty-nine participants with COPD were enrolled in a longitudinal cohort study, and data from the 601 participant days that occurred during the warm weather season were included in the analysis. Participants completed home environmental monitoring with measurement of temperature, relative humidity, and indoor air pollutants and simultaneous daily assessment of respiratory health with questionnaires and portable spirometry. MEASUREMENTS AND MAIN RESULTS: Participants had moderate to severe COPD and spent the majority of their time indoors. Increases in maximal indoor temperature were associated with worsening of daily Breathlessness, Cough, and Sputum Scale scores and increases in rescue inhaler use. The effect was detected on the same day and lags of 1 and 2 days. The detrimental effect of temperature on these outcomes increased with higher concentrations of indoor fine particulate matter and nitrogen dioxide (P < 0.05 for interaction terms). On days during which participants went outdoors, increases in maximal daily outdoor temperature were associated with increases in Breathlessness, Cough, and Sputum Scale scores after adjusting for outdoor pollution concentrations. CONCLUSIONS: For patients with COPD who spend the majority of their time indoors, indoor heat exposure during the warmer months represents a modifiable environmental exposure that may contribute to respiratory morbidity. In the context of climate change, adaptive strategies that include optimization of indoor environmental conditions are needed to protect this high risk group from the adverse health effects of heat. PMID- 27684433 TI - 1,3-Oxazole derivatives as potential anticancer agents: Computer modeling and experimental study. AB - Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the microtubule assemblies has emerged as one of the most promising cancer treatment strategies. Predictive QSAR models were built on a series of selective inhibitors of the tubulin were performed by using Associative Neural Networks (ANN). To overcome the problem of data overfitting due to the descriptor selection, a 5-fold cross-validation with variable selection in each step of the analysis was used. All developed QSAR models showed excellent statistics on the training (total accuracy: 0.96-0.97) and test sets (total accuracy: 0.95-97). The models were further validated by 11 synthesized 1,3-oxazole derivatives and all of them showed inhibitory effect on the Hep-2 cancer cell line. The most promising compound showed inhibitory activity IC50=60.2MUM. In order to hypothesize their mechanism of action the top three compounds were docked in the colchicine binding site of tubulin and showed reasonable docking scores as well as favorable interactions with the protein. PMID- 27684434 TI - Individual and developmental differences in preschoolers' categorization biases and vocabulary across tasks. AB - This study bridges prior research on young children's use of taxonomic versus thematic relations to categorize objects with prior research on their use of shared shape versus shared function to categorize artifacts. Specifically, this research examined associations in children's categorization tendencies across these two dichotomies, including assessments of individual differences, developmental trends, and vocabulary level. Preschoolers (3- to 5-year-olds) completed a receptive vocabulary assessment and two match-to-sample tasks: one pitting (superordinate) taxonomic and thematic relations against each other and one pitting shape and function similarity against each other. The results revealed individual and developmental variation in children's cross-task categorization biases, with a predominant tendency to focus on both thematic and function relations that became increasingly stronger with age. In 3- and 5-year olds, function-based categorization was also positively associated with verb vocabulary. These findings demonstrate an emerging tendency to focus on relational information during the preschool years that, among other learning effects, may benefit verb acquisition. The results are discussed in terms of the real-time processing and developmental factors that might contribute to the development of strategies for learning about objects and categories during early childhood. PMID- 27684436 TI - Study of the Relationship between Boundary Slip and Nanobubbles on a Smooth Hydrophobic Surface. AB - Surface nanobubbles, which are nanoscopic or microscopic gaseous domains forming at the solid/liquid interface, have a strong impact on the interface by changing the two-phase contact to a three-phase contact. Therefore, they are believed to affect the boundary condition and liquid flow. However, there are still disputes in the theoretical studies as to whether the nanobubbles can increase the slip length effectively. Furthermore, there are still no direct experimental studies to support either side. Therefore, an intensive study on the effective slip length for flows over bare surfaces with nanobubbles is essential for establishing the relation between nanobubbles and slip length. Here, we study the effect of nanobubbles on the slippage experimentally and theoretically. Our experimental results reveal an increase from 8 to 512 nm in slip length by increasing the surface coverage of nanobubbles from 1.7 to 50.8% and by decreasing the contact angle of nanobubbles from 42.8 to 16.6 degrees . This is in good agreement with theoretical results. Our results indicate that nanobubbles could always act as a lubricant and significantly increase the slip length. The surface coverage, height, and contact angle are key factors for nanobubbles to reduce wall friction. PMID- 27684435 TI - In-depth Physiological Analysis of Defined Cell Populations in Acute Tissue Slices of the Mouse Vomeronasal Organ. AB - In most mammals, the vomeronasal organ (VNO) is a chemosensory structure that detects both hetero- and conspecific social cues. Vomeronasal sensory neurons (VSNs) express a specific type of G protein-coupled receptor (GPCR) from at least three different chemoreceptor gene families allowing sensitive and specific detection of chemosensory cues. These families comprise the V1r and V2r gene families as well as the formyl peptide receptor (FPR)-related sequence (Fpr-rs) family of putative chemoreceptor genes. In order to understand the physiology of vomeronasal receptor-ligand interactions and downstream signaling, it is essential to identify the biophysical properties inherent to each specific class of VSNs. The physiological approach described here allows identification and in depth analysis of a defined population of sensory neurons using a transgenic mouse line (Fpr-rs3-i-Venus). The use of this protocol, however, is not restricted to this specific line and thus can easily be extended to other genetically modified lines or wild type animals. PMID- 27684438 TI - Joint acute and endocrine disruptive toxicities of malathion, cypermethrin and prochloraz to embryo-larval zebrafish, Danio rerio. AB - It remains a daunting challenge to determine ecotoxicological risks of exposure to mixtures of endocrine disrupting chemicals (EDCs) in environmental toxicology. In the present study, we investigated acute and endocrine disruptive toxicities of cypermethrin (CPM), malathion (MAL), prochloraz (PRO) and their binary mixtures of MAL + CPM and MAL + PRO to the early life stages of zebrafish. In the acute lethal toxicity test, three pesticides exhibited different levels of toxicity to zebrafish larvae, and the order of toxicity was as follows: CPM > PRO > MAL. The binary mixture of MAL + CPM displayed a synergistic effect on zebrafish larvae after exposure for 24, 48, 72 and 96 h. However, binary mixture of MAL + PRO showed an antagonistic effect. To evaluate the estrogenic effect, the expression of genes in the hypothalamic-pituitary-gonadal axis was assessed after zebrafish embryos were exposed to CPM, MAL, PRO and their binary mixtures from blastula stage (1 h post-fertilization, 1 hpf) to 14 dpf (14 d post fertilization). Our data indicated that the transcription patterns of many key genes (vtg1, vtg2, era, erbeta1, erbeta2, cyp19a1a and cyp19a1b) were affected in hatched zebrafish after exposure to CPM, MAL and PRO. Moreover, following exposure to binary mixtures of 1000 MUg/L MAL +4 MUg/L CPM and 1000 MUg/L MAL +900 MUg/L PRO, the gene expressions were significantly changed compared with the individual pesticides. Our data provided a better understanding of bidirectional interactions of toxic response induced by these pesticides. PMID- 27684437 TI - Actinobacteria: Current research and perspectives for bioremediation of pesticides and heavy metals. AB - Actinobacteria exhibit cosmopolitan distribution since their members are widely distributed in aquatic and terrestrial ecosystems. In the environment they play relevant ecological roles including recycling of substances, degradation of complex polymers, and production of bioactive molecules. Biotechnological potential of actinobacteria in the environment was demonstrated by their ability to remove organic and inorganic pollutants. This ability is the reason why actinobacteria have received special attention as candidates for bioremediation, which has gained importance because of the widespread release of contaminants into the environment. Among organic contaminants, pesticides are widely used for pest control, although the negative impact of these chemicals in the environmental balance is increasingly becoming apparent. Similarly, the extensive application of heavy metals in industrial processes lead to highly contaminated areas worldwide. Several studies focused in the use of actinobacteria for cleaning up the environment were performed in the last 15 years. Strategies such as bioaugmentation, biostimulation, cell immobilization, production of biosurfactants, design of defined mixed cultures and the use of plant-microbe systems were developed to enhance the capabilities of actinobacteria in bioremediation. In this review, we compiled and discussed works focused in the study of different bioremediation strategies using actinobacteria and how they contributed to the improvement of the already existing strategies. In addition, we discuss the importance of omic studies to elucidate mechanisms and regulations that bacteria use to cope with pollutant toxicity, since they are still little known in actinobacteria. A brief account of sources and harmful effects of pesticides and heavy metals is also given. PMID- 27684439 TI - Fast Pyrolysis of Biomass Residues in a Twin-screw Mixing Reactor. AB - Fast pyrolysis is being increasingly applied in commercial plants worldwide. They run exclusively on woody biomass, which has favorable properties for conversion with fast pyrolysis. In order to increase the synergies of food production and the energetic and/or material use of biomass, it is desirable to utilize residues from agricultural production, e.g., straw. The presented method is suitable for converting such a material on an industrial scale. The main features are presented and an example of mass balances from the conversion of several biomass residues is given. After conversion, fractionated condensation is applied in order to retrieve two condensates - an organic-rich and an aqueous-rich one. This design prevents the production of fast pyrolysis bio-oil that exhibits phase separation. A two phase bio-oil is to be expected because of the typically high ash content of straw biomass, which promotes the production of water of reaction during conversion. Both fractionated condensation and the use of biomass with high ash content demand a careful approach for establishing balances. Not all kind of balances are both meaningful and comparable to other results from the literature. Different balancing methods are presented, and the information that can be derived from them is discussed. PMID- 27684441 TI - Hospitalisations with Hidradenitis Suppurativa: An Increasing Problem That Deserves Closer Attention. AB - BACKGROUND/AIMS: Hidradenitis suppurativa (HS), a chronic inflammatory skin disease of the hair follicle, can lead to scarring and disability. With an estimated European prevalence of 1%, few epidemiological studies of HS have been performed, and none focused on hospitalisations. We aimed to study the time trends of HS hospitalisations and to evaluate the demographic characteristics, hospital incidence rate, readmissions, length of stay, comorbidities and risk factors of hospitalised HS patients. METHODS: We performed a retrospective observational study using a national administrative database in Portugal, with discharges between 2000 and 2014. All the inpatients aged 5 years or more with a diagnosis of HS were included. Variables analysed were age, sex, admission and discharge date, discharge outcome and diagnoses. RESULTS: A total of 1,177 patients were hospitalised in this time period (48 were aged 18 years or younger) with a male-to-female ratio of 1:1.17. There was a hospital incidence rate of 0.83 patients with HS per 100,000 person-years (95% CI = 0.78-0.88). The age group with the highest incidence rate was 20-29 years among women and 40-49 years among men. We recorded an increasing trend in the number of new hospitalised patients and in the hospital incidence rate of HS. Tobacco was the most common comorbidity/risk factor. Eighty-three percent of our population underwent HS surgery. CONCLUSION: This hospital-based incidence study showed that admission for HS is increasing and that the majority of the HS inpatients were surgical cases. In the future, prospective studies will be important to assess risk factors for hospitalisations and complications. PMID- 27684442 TI - Characterization of Heterocoagulation with Oppositely Charged Polymer Colloid Particles through Online Tracking of Light Transmittance. AB - Heterocoagulation of colloid particles with opposite surface charge has been used for the preparation of composite microspheres with specifically designed suprastructure, such as those with raspberry-like surface morphology and core shell microspheres, which are difficult to achieve through other techniques. Here we report our investigation on the heterocoagulation of cationic polystyrene (PS) particles with anionic poly(methyl methacrylate) (PMMA) particles by a novel technique, i.e., by following online the evolution of the light transmittance in the process with practically no disturbance of the dispersion and no post treatment for the samples. Different heterocoagulations were conducted with PS and PMMA latexes with different latex mixing regimes and different particle sizes for both latexes. The evolution of the light transmittance in all of these processes, mainly with addition of anionic latex to cationic latex, was followed online. By combining TEM to detect the morphology of the composite microspheres formed and light scattering to follow the size evolution in the heterocoagulation, this work gives a clear picture of the heterocoagulation process. In addition, a set of mathematical equations are established in order to estimate the number ratio of the particles with opposite charge and the surface coverage percent of the large primary particle with the small ones. Results show that the particle size plays a key role in the process. The mechanism of the heterocoagulation process is discussed. PMID- 27684440 TI - An Open-Label Pilot Study of Metformin as a Concomitant Therapy on Patients with Prostate Cancer Undergoing Androgen Deprivation Treatment. AB - PURPOSE: The study aimed to evaluate the effects of metformin on insulin, C peptide and body weight in Chinese men undergoing androgen deprivation therapy (ADT). METHODS: Between March 2013 and June 2014, 62 newly diagnosed patients of prostate cancer (PCa) due to receive ADT were recruited from 7 hospitals in Shanghai. Patients were randomized to respectively receive ADT (n = 31) and ADT + metformin (n = 31) for 6 months. Fasting and postprandial serum levels of insulin and C-peptide, blood glucose, prostate specific antigen, body mass index (BMI) and waist circumference (WC) were measured at the beginning and end of 6-month treatment. RESULTS: Baseline characteristics were comparable between the 2 groups. Controlling for baseline levels, the ADT group had significantly higher levels of fasting glucose (p = 0.01) and higher WC (p = 0.04) than the ADT + metformin group. The levels of insulin, C-peptide and BMI did not differ significantly. CONCLUSIONS: Metformin may be potentially efficient as a concomitant therapy on patients with PCa undergoing androgen deprivation treatment. PMID- 27684443 TI - Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition. AB - Competitive exclusion can occur in microbial communities when, for example, an inhibitor-producing strain outcompetes its competitor for an essential nutrient or produces antimicrobial compounds that its competitor is not resistant to. Here we describe a deferred growth inhibition assay, a method for assessing the ability of one bacterium to inhibit the growth of another through the production of antimicrobial compounds or through competition for nutrients. This technique has been used to investigate the correlation of nasal isolates with the exclusion of particular species from a community. This technique can also be used to screen for lantibiotic producers or potentially novel antimicrobials. The assay is performed by first culturing the test inhibitor-producing strain overnight on an agar plate, then spraying over the test competitor strain and incubating again. After incubation, the extent of inhibition can be measured quantitatively, through the size of the zone of clearing around the inhibitor-producing strain, and qualitatively, by assessing the clarity of the inhibition zone. Here we present the protocol for the deferred inhibition assay, describe ways to minimize variation between experiments, and define a clarity scale that can be used to qualitatively assess the degree of inhibition. PMID- 27684444 TI - Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability. AB - The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data are scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict Fub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18Fub. The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0.11 0.14), and acids (MAE 0.14-0.17). A consensus model had the highest accuracy across both pharmaceuticals (MAE 0.151-0.155) and environmentally relevant chemicals (MAE 0.110-0.131). The inclusion of the majority of the ToxCast test sets within the AD of the consensus model, coupled with high prediction accuracy for these chemicals, indicates the model provides a QSAR for Fub that is broadly applicable to both pharmaceuticals and environmentally relevant chemicals. PMID- 27684445 TI - Plasmon-Enhanced Sub-Bandgap Photocatalysis via Triplet-Triplet Annihilation Upconversion for Volatile Organic Compound Degradation. AB - This study demonstrates the first reported photocatalytic decomposition of an indoor air pollutant, acetaldehyde, using low-energy, sub-bandgap photons harnessed through sensitized triplet-triplet annihilation (TTA) upconversion (UC). To utilize low-intensity noncoherent indoor light and maximize photocatalytic activity, we designed a plasmon-enhanced sub-bandgap photocatalyst device consisting of two main components: (1) TTA-UC rubbery polymer films containing broad-band plasmonic particles (Ag-SiO2) to upconvert sub-bandgap photons, and (2) nanodiamond (ND)-loaded WO3 as a visible-light photocatalyst composite. Effective decomposition of acetaldehyde was achieved using ND/WO3 (Eg = 2.8 eV) coupled with TTA-UC polymer films that emit blue photons (lambdaEm = 425 nm, 2.92 eV) upconverted from green photons (lambdaEx = 532 nm, 2.33 eV), which are wasted in most environmental photocatalysis. The overall photocatalytic efficiency was amplified by the broad-band surface plasmon resonance of AgNP-SiO2 particles incorporated into the TTA-UC films. PMID- 27684448 TI - Efficient Blue Electroluminescence Using Quantum-Confined Two-Dimensional Perovskites. AB - Solution-processed hybrid organic-inorganic lead halide perovskites are emerging as one of the most promising candidates for low-cost light-emitting diodes (LEDs). However, due to a small exciton binding energy, it is not yet possible to achieve an efficient electroluminescence within the blue wavelength region at room temperature, as is necessary for full-spectrum light sources. Here, we demonstrate efficient blue LEDs based on the colloidal, quantum-confined 2D perovskites, with precisely controlled stacking down to one-unit-cell thickness (n = 1). A variety of low-k organic host compounds are used to disperse the 2D perovskites, effectively creating a matrix of the dielectric quantum wells, which significantly boosts the exciton binding energy by the dielectric confinement effect. Through the Forster resonance energy transfer, the excitons down-convert and recombine radiatively in the 2D perovskites. We report room-temperature pure green (n = 7-10), sky blue (n = 5), pure blue (n = 3), and deep blue (n = 1) electroluminescence, with record-high external quantum efficiencies in the green to-blue wavelength region. PMID- 27684447 TI - Effectiveness of the live attenuated and the inactivated influenza vaccine in two year-olds - a nationwide cohort study Finland, influenza season 2015/16. AB - Although widely recommended, influenza vaccination of children is part of the national vaccination programme only in few countries. In addition to Canada and the United States (US), in Europe Finland and the United Kingdom have introduced live attenuated influenza vaccine (LAIV) for healthy children in their programmes. On 22 June 2016, the US Advisory Committee on Immunizations Practices, voted against further use of LAIV due to no observed vaccine effectiveness (VE) over three consecutive influenza seasons (2013/14 to 2015/16). We summarise the results of a nationwide, register-based cohort study (N=55,258 of whom 8,086 received LAIV and 4,297 TIV); all outcome (laboratory-confirmed influenza), exposure (vaccination) and confounding variable data were retrieved from four computerised national health registers, which were linked via a unique personal identity code assigned to all permanent Finnish residents regardless of nationality. Our study provides evidence of moderate effectiveness against any laboratory-confirmed influenza of the quadrivalent LAIV vaccine (VE: 51%; 95% confidence interval (CI): 28-66%) as well as the inactivated trivalent vaccine (VE: 61%; 95% CI: 31-78%) among two-year-olds during the influenza season 2015/16 in Finland. Based on these data, Finland will continue using LAIV for young children in its National Immunisation Programme this coming influenza season. PMID- 27684446 TI - In Vitro Transcription Assays and Their Application in Drug Discovery. AB - In vitro transcription assays have been developed and widely used for many years to study the molecular mechanisms involved in transcription. This process requires multi-subunit DNA-dependent RNA polymerase (RNAP) and a series of transcription factors that act to modulate the activity of RNAP during gene expression. Sequencing gel electrophoresis of radiolabeled transcripts is used to provide detailed mechanistic information on how transcription proceeds and what parameters can affect it. In this paper we describe the protocol to study how the essential elongation factor NusA regulates transcriptional pausing, as well as a method to identify an antibacterial agent targeting transcription initiation through inhibition of RNAP holoenzyme formation. These methods can be used a as platform for the development of additional approaches to explore the mechanism of action of the transcription factors which still remain unclear, as well as new antibacterial agents targeting transcription which is an underutilized drug target in antibiotic research and development. PMID- 27684449 TI - Consistent and cumulative effects of syntactic experience in children's sentence production: Evidence for error-based implicit learning. AB - Error-based implicit learning models (e.g., Chang, Dell, & Bock, 2006) propose that a single learning mechanism underlies immediate and long-term effects of experience on children's syntax. We test two key predictions of these models: That individual experiences of infrequent structures should yield both immediate and long-term facilitation, and that such learning should be consistent in individual speakers across time. Children (and adults) described transitive events in two picture-matching games, held a week apart. In both sessions, the experimenter's immediately preceding syntax (active vs. passive) dynamically influenced children's (and adults') syntactic choices in an individually consistent manner. Moreover, children showed long-term facilitation, through an increased likelihood to produce passives in Session 2, with speakers who were most likely to immediately repeat passives in Session 1 being most likely to produce passives in Session 2. Our results are consistent with an error-based syntactic learning mechanism that operates across the lifespan. PMID- 27684450 TI - Brightly Luminescent and Kinetically Inert Lanthanide Bioprobes Based on Linear and Preorganized Chelators. AB - The synthesis, photophysical properties, and kinetic stability of a series of water-soluble, highly emissive Tb(III) and Eu(III) complexes featuring triethylenetetraamine hexaacetic acid (TTHA) and cyclohexyl triethylenetetraamine hexaacetic acid (cyTTHA) chelator scaffolds and carbostyril sensitizers are reported. The unique and modular design of the chelators gives rise to striking quantum yields of emission in aqueous solutions (up to 54%) as well as the characteristic lanthanides' photophysical properties (long excited-state lifetimes, large effective Stokes shifts, and narrow emission peaks). Furthermore, the preorganized chelators (L3, L4, and L6) bind metal within minutes at ambient temperature yet exhibit substantial resistance to transchelation in the presence of a challenge solution (EDTA, 1 mM). Moreover, the Eu(III) complex of L4 remains stably luminescent in HeLa cells over hours, demonstrating the suitability of these compounds for live-cell imaging applications. Representative chelators suitable for derivatization and protein bioconjugation were also prepared that were functionalized with clickable azide and alkyne moieties, biotin, and trimethoprim (TMP). With exceptional long wavelength brightness, enhanced kinetic inertness, and an adaptable synthetic route, the reported lanthanide complexes are promising probes and labels for time gated bioanalysis, biosensing, and optical microscopy. PMID- 27684451 TI - Multi-pass Monte Carlo simulation method in nuclear transmutations. AB - Monte Carlo methods, in their direct brute simulation incarnation, bring realistic results if the involved probabilities, be they geometrical or otherwise, remain constant for the duration of the simulation. However, there are physical setups where the evolution of the simulation represents a modification of the simulated system itself. Chief among such evolving simulated systems are the activation/transmutation setups. That is, the simulation starts with a given set of probabilities, which are determined by the geometry of the system, the components and by the microscopic interaction cross-sections. However, the relative weight of the components of the system changes along with the steps of the simulation. A natural measure would be adjusting probabilities after every step of the simulation. On the other hand, the physical system has typically a number of components of the order of Avogadro's number, usually 1025 or 1026 members. A simulation step changes the characteristics for just a few of these members; a probability will therefore shift by a quantity of 1/1025. Such a change cannot be accounted for within a simulation, because then the simulation should have then a number of at least 1028 steps in order to have some significance. This is not feasible, of course. For our computing devices, a simulation of one million steps is comfortable, but a further order of magnitude becomes too big a stretch for the computing resources. We propose here a method of dealing with the changing probabilities, leading to the increasing of the precision. This method is intended as a fast approximating approach, and also as a simple introduction (for the benefit of students) in the very branched subject of Monte Carlo simulations vis-a-vis nuclear reactors. PMID- 27684452 TI - Determination of 137Cs half-life with an ionization chamber. AB - The half-life of 137Cs was measured with an ionization chamber by following the decay of 5 sources over a 30 years period between 1983 and 2013. The ratio between the ionization chamber current for the cesium sources and 226Ra source was used for the half-life calculation. The value found for the 137Cs half-life is 10,955.2+/-10.7 days, where the uncertainty evaluation combines type A and B for one standard deviation. PMID- 27684453 TI - Study of the elemental composition of saliva of smokers and nonsmokers by X-ray fluorescence. AB - Cigarette smoking is a serious public health problem. According to data from the World Health Organization, it is estimated that currently more than 1.2 billion people worldwide do tobacco use and that smoking-related diseases are responsible for about 6 million deaths each. With attention to this, it is necessary to seek preventive and prognostic of trying to reduce these numbers and alert the public in general about the danger and the harm caused by its use. Thus, the objective of the research work undertaken was to evaluate and compare the chemical composition of collected saliva samples of smokers and nonsmokers by X-ray Fluorescence analyses. 32 individuals were selected, 16 of which used cigarette on a daily basis and the other 16 had never smoked. Saliva was collected with the help of a (sterile) disposable Pasteur pipette and samples sent to the Applied Nuclear Physics Laboratory at UNISO (LAFINAU), where analyzes were carried out. Individuals who agreed to participate in the study answered a questionnaire to define their profile of inclusion and signed an informed consent form (CEP Protocol no. 831.753 of 09/10/2014). The results clearly showed that there are differences in the concentrations of chemical elements in the saliva of smokers and non-smokers. The biggest discrepancies were found at concentrations of the chemical elements Sulfur, Phosphorus, Chlorine and Potassium, and smaller differences in the concentration of the elements Calcium, Manganese, Iron, Copper, Titanium, Vanadium and Nickel. In only one saliva sample, and in quite low amounts, arsenic was detected. The results indicate that smoking produces more significant changes in the saliva of women than in men, increasing the concentration of some elements in the saliva of female smokers, much more than in the male smokers. The cigarette usage time also appears to exert a greater influence on the composition of the saliva of women than in men, indicating that the damage caused by cigarette use may in fact be higher in women than in men. PMID- 27684454 TI - A parameterization of the chemistry-normality dependence of bulk etch rate in a CR-39 detector. AB - An empirical relationship describing the bulk etch rate is formulated. The equation involves two free fitting parameters, which reproduce the bulk etch rate for CR-39 by alpha particles at different normalities of the etching solution. The values of the fitting parameters were obtained from the experimental data. This relationship is used to predict the bulk etch rate at different normalities. PMID- 27684455 TI - Durable Response of Metastatic Squamous Cell Carcinoma of the Skin to Ipilimumab Immunotherapy. AB - A 72-year-old male patient was receiving second-line chemotherapy for metastatic squamous cell carcinoma of the skin (SCCS) when he was diagnosed with concurrent metastatic melanoma (BRAF mutant). Chemotherapy was ceased and he was treated with 4 cycles of ipilimumab immunotherapy. The patient experienced clinical benefit and durable remission in both malignancies and remains free of cancer progression 8 months after the last cycle of ipilimumab. Response of SCCS to ipilimumab has not been previously described, however this case and recent reports of pembrolizumab efficacy confirm the critical role of the immune system in SCCS pathogenesis and suggest further exploration of checkpoint immunotherapy for the treatment of this disease. PMID- 27684456 TI - Sit-to-stand-and-walk from 120% Knee Height: A Novel Approach to Assess Dynamic Postural Control Independent of Lead-limb. AB - Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: STW). Thus, in clinical rehabilitation separation of sit-to-stand and gait initiation - termed sit-to-stand-and-walk (STSW) - is usual. However, a standardized STSW protocol with a clearly defined analytical approach suitable for pathological assessment has yet to be defined. Hence, a goal-orientated protocol is defined that is suitable for healthy and compromised individuals by requiring the rising phase to be initiated from 120% knee height with a wide base of support independent of lead limb. Optical capture of three-dimensional (3D) segmental movement trajectories, and force platforms to yield two-dimensional (2D) center of-pressure (COP) trajectories permit tracking of the horizontal distance between COP and whole-body-center-of-mass (BCOM), the decrease of which increases positional stability but is proposed to represent poor dynamic postural control. BCOM-COP distance is expressed with and without normalization to subjects' leg length. Whilst COP-BCOM distances vary through STSW, normalized data at the key movement events of seat-off and initial toe-off (TO1) during steps 1 and 2 have low intra and inter subject variability in 5 repeated trials performed by 10 young healthy individuals. Thus, comparing COP-BCOM distance at key events during performance of an STSW paradigm between patients with upper motor neuron injury, or other compromised patient groups, and normative data in young healthy individuals is a novel methodology for evaluation of dynamic postural stability. PMID- 27684457 TI - Effect of Bevacizumab Plus Temozolomide-Radiotherapy for Newly Diagnosed Glioblastoma with Different MGMT Methylation Status: A Meta-Analysis of Clinical Trials. AB - BACKGROUND MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. MATERIAL AND METHODS Data were extracted from publications in PubMed, Embase, and The Cochrane Library, with the last search performed March 23, 2016. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained. RESULTS Data from 3 clinical trials for a total of 1443 subjects were used for this meta-analysis. MGMT methylated and unmethylated patients showed improved PFS in the BV group (pooled HRs, 0.769, 95% CIs 0.604-0.978, P=0.032; 0.675, 95%CIs 0.466-0.979, P=0.038). For patients with either type of GBM, BV did not improve the OS based on the pooled HRs 1.132 (95% CIs 0.876-1.462; P=0.345) for methylated and 1.018 (95% CIs 0.879-1.179; P=0.345) for unmethylated. CONCLUSIONS Bevacizumab combined with temozolomide-radiotherapy correlated with improved PFS for treatment of patients with different MGMT methylation status of newly diagnosed GBM. There was insufficient evidence to determine the synergistic effects of combining BV with TMZ and RT on improving survival in patients with different MGMT methylation status. PMID- 27684458 TI - Effects of Combined Photodynamic Therapy and Topical Bevacizumab Treatment on Corneal Neovascularization in Rabbits. AB - PURPOSE: To evaluate the effects of combined photodynamic therapy (PDT) and topical bevacizumab treatment on corneal neovascularization in rabbits. METHODS: Corneal neovascularization was induced by placing a suture for 7 days in both eyes of 15 rabbits. After suture removal, the right eyes of the rabbits were divided into 3 treatment groups (n = 5 each): group 1, 5 mg/mL bevacizumab eye drops; group 2, PDT at 150 J/cm; and group 3, combined PDT and topical bevacizumab treatment. All 15 left eyes formed a control group. After 2 weeks of treatment, digital photographs were obtained and analyzed to determine the area of corneal neovascularization. The rabbits were then killed to measure vascular endothelial growth factor (VEGF) levels in corneal tissues. RESULTS: The corneal neovascularization area after treatment was significantly smaller in the 3 treatment groups compared with that in the control group. A significant difference was observed between groups 1 and 2 and group 3, but not between groups 1 and 2. VEGF levels were significantly lower in groups 1 and 3 than in the control group. Although group 2 exhibited relatively higher VEGF levels compared with the control group, the difference was not significant. CONCLUSIONS: Our results suggest that combined PDT and topical bevacizumab treatment is significantly more effective than monotherapy for the treatment of corneal neovascularization in rabbits. Such quantitative comparison in the laboratory is believed to provide the theoretical basis for clinical application of combined PDT and topical bevacizumab treatment. PMID- 27684459 TI - Surgical Drainage of Lymphangiectasia Haemorrhagica Conjunctivae. AB - PURPOSE: To report a case of nonresolving lymphangiectasia haemorrhagica conjunctivae (LHC) successfully treated with surgical drainage. METHODS: Retrospective case report. RESULTS: A 17-year-old white girl presented with a history of a large red lesion affecting her right eye. Approximately 1 year earlier, she had noticed a small painless "red spot" affecting the inferior aspect of the conjunctiva of her right eye. Three months before presentation, she noticed a sudden increase in the size of the lesion. There was no history of trauma, and she was not a contact lens wearer. Her medical history was remarkable for a remote seizure disorder which had been stable on levetiracetam. Magnetic resonance imaging/magnetic resonance angiography of the brain and orbits was unremarkable. Anterior segment fluorescein angiography did not show any flow in the lesion, indicating a lymphatic origin of channels. Surgical drainage of the lesion was performed while sparing the affected conjunctiva resulting in an excellent cosmetic outcome. Incisional biopsy confirmed the diagnosis of LHC. The patient remained free of recurrence 6 months after the procedure. CONCLUSIONS: Nonresolving LHC can be managed successfully with conjunctival sparing surgical drainage with an excellent cosmetic outcome. PMID- 27684460 TI - Association Between Conjunctival and Corneal Calcification and Atherosclerotic Changes in the Carotid Artery in Maintenance Hemodialysis Patients. AB - PURPOSE: We aimed to investigate the association between atherosclerotic changes in the common carotid artery (CA) and conjunctival and corneal calcification (CCC) in maintenance hemodialysis (MHD) patients. METHODS: Fifty eyes of MHD patients with the highest CCC scores were enrolled. CCCs were scored according to the method described by Tokuyama et al. The eyes with the highest CCC scores were selected for further analysis. According to their CCC scores, the patients were classified into 3 groups: mild (0-2 score), moderate (3-5), and severe (6-10 score). Atherosclerosis of the common CA was evaluated by determination of intima media thickness (IMT), peak systolic (PSV) and end diastolic (EDV) flow velocities, pulsatility index, and resistive index values by using Doppler ultrasonography. RESULTS: The mean IMT of the CA was 0.61 +/- 0.09 mm in the mild group, 0.82 +/- 0.16 mm in the moderate group, and 1.21 +/- 0.32 mm in the severe group (P < 0.001). The PSV and EDV were significantly higher in the severe group than in the mild and moderate groups (all, P < 0.001). The CCC score was positively correlated with the duration of hemodialysis, ocular surface disease index score, IMT, PSV, EDV, lymphocyte, calcium, and sedimentation rate. In multiple stepwise linear regression analysis, IMT was the best predictive factor for the CCC score (R = 0.812, beta = 9.526 +/- 1.05, and P < 0.001). CONCLUSIONS: Our results suggest that chronic ocular ischemia due to atherosclerotic changes may have a role in the formation or progression of CCC in MHD patients. PMID- 27684461 TI - Factors Influencing the Quality of the Donor Cornea. PMID- 27684462 TI - Extent of Resection and Survival in Glioblastoma Multiforme-Reply. PMID- 27684463 TI - Prognostic value of circulating microRNA-21 for breast cancer: a systematic review and meta-analysis. AB - BACKGROUND: There is an urgent need for novel noninvasive prognostic molecular tumor marker for monitoring the recurrence of breast cancer. MicroRNA-21 (miR-21) play a crucial role in the progression and aggressiveness of breast cancer, but its prognostic significance for patients with breast cancer remains inconclusive. The aim of this meta-analysis is to summarize the role of circulating miR-21 as a molecular marker in patients with breast cancer. MATERIAL AND METHODS: Eligible studies were searched from the PubMed, EMBASE and Web of Science databases. The chi2 and I2 tests were used to evaluate heterogeneity between studies. The pooled hazard ratios (HR) with 95% confidence interval (CI) were calculated by a fixed effects model, if no heterogeneity existed. If there was heterogeneity, a random effects model was applied. The meta-analysis was conducted using the Review Manager 5 software. RESULTS: A total of 7 articles which included 1629 cases were selected for the meta-analysis. Elevated miR-21 expression was significantly predictive of poor overall survival (HR = 1.51, 95%CI 1.15-1.98, p = 0.003). The subgroup analysis consisted of in tissue sample (HR = 1.66, 95%CI 1.03-2.67, p = 0.04) and serum sample (HR = 1.73, 95%CI 1.22-2.46, p = 0.002). The association between miR-21 expression level and lymph node metastasis was statistically significant (OR = 2.36, 95%CI 1.04-4.78, p = 0.03). CONCLUSION: Our findings suggest that the circulating miR-21 expression level can predict poor prognosis in patients with breast cancer. PMID- 27684464 TI - Device Life of the Tracheoesophageal Voice Prosthesis Revisited. AB - Importance: Voice prosthesis (VP) device life is a limiting factor of tracheoesophageal (TE) voice restoration that drives patient satisfaction, health care costs, and overall burden. Historic data suggest that TE VPs have an average device life of generally 3 to 6 months, but these data are typically derived from small samples using only 1 or 2 devices. Objective: To reexamine current device life in a large, contemporary cancer hospital in the United States that uses a wide assortment of VPs. Design, Setting, and Participants: This retrospective observational study included 390 laryngectomized patients with a tracheoesophageal puncture (TEP) who had VP management at MD Anderson Cancer Center between July 1, 2003, and December 31, 2013. Main Outcomes and Measures: Tracheoesophageal voice-related outcomes were: (1) device life duration to VP removal, and (2) treatment-related and prosthetic-related factors influencing device failure. Primary independent variables included treatment history (extent of surgery and radiation history), VP type (indwelling vs nonindwelling, size, specialty features), and reason for removal (leakage, complication, other). Duration was examined using Kaplan-Meier analysis. Disease, treatment, and patient-specific factors were analyzed as predictors of duration. Results: Overall, 3648 VPs were placed in the 390 patients (median [range] age, 62 [34-92] years). Indwelling prostheses accounted for more than half (56%) of the devices placed (55%, 20-Fr diameter; 33%, 8-mm length). More than two-thirds (69%) of prostheses were removed because of leakage, while the rest were removed for other reasons. Median device life was 61 days for all prostheses. Indwelling and nonindwelling VPs had median device lives of 70 and 38 days, respectively. There was no significant difference between specialty prostheses compared with standard devices (median duration, 61 vs 70 days, respectively). The Provox ActiValve (Atos Medical) had the longest life. Neither radiation therapy nor extent of surgery had a meaningful impact on device life. Conclusions and Relevance: Our data suggest that VP duration demonstrates a lower durability than historically reported. This may reflect the intensification of treatment regimens that complicate TEP management in an era of organ preservation; however, further investigation is needed. PMID- 27684465 TI - Brain-computer interface for individuals after spinal cord injury. AB - PURPOSE/OBJECTIVE: To investigate the feasibility of brain-computer interface (BCI) with patients on an inpatient spinal cord injury (SCI) unit. Research Method/Design: This study included 25 participants aged 18-64 who sustained traumatic or nontraumatic SCI and did not have severe cognitive or psychiatric impairment. Participants completed a variety of screening measures related to cognition, psychological disposition, pain, and technology experience/interest. The Emotiv electroencephalography system was used in conjunction with a cube rotation and manipulation game presented on a laptop computer. RESULTS: The majority of participants successfully completed the BCI game and reported enjoyment of the experience. Outside of a mild trend of lower performance among participants with a past or present head injury, there were no demographic variables, injury variables or screening measures significantly associated with BCI performance. CONCLUSIONS/IMPLICATIONS: The BCI paradigm demonstrated feasibility and safety across participant age range, educational and vocational background, and level of injury. Despite the rapid integration of technology into rehabilitation health care settings, there are few evidence-based studies regarding the feasibility of technology with specific inpatient populations. Clinical implications and challenges of using this technology in a rehabilitation setting are discussed. (PsycINFO Database Record PMID- 27684466 TI - Reply to letter by Beyan and Beyan. PMID- 27684467 TI - Corrigendum. PMID- 27684469 TI - The effect of vildagliptin relative to sulfonylurea as dual therapy with metformin (or as monotherapy) in Muslim patients with type 2 diabetes fasting during Ramadan in the Middle East: the VIRTUE study. AB - OBJECTIVE: To assess the effect of vildagliptin relative to sulfonylurea (SU) on hypoglycemic events, in Muslim patients from the Middle East with type 2 diabetes who fast during Ramadan. The primary endpoint was the proportion of patients with at least one hypoglycemic event (HE) during the fasting period. Secondary endpoints included change in weight, HbA1c levels, treatment adherence and overall safety. DESIGN AND METHODS: This multicenter, prospective, observational cohort study enrolled Muslim adult T2DM patients from Middle Eastern countries who received treatment with vildagliptin or SU as add on to metformin or monotherapy. During a ~16 week observation period, data was collected up to 6 weeks before and 6 weeks after Ramadan fasting. RESULTS: A total of 584 patients from the Middle East enrolled in the study; 308 patients received vildagliptin and 265 received SU. Significantly fewer vildagliptin patients reported at least one HE (3.7% vildagliptin vs. 25.5% SU; p < .001). No grade 2 HEs were reported in vildagliptin patients versus two in SU patients (p = .128). Mean change in HbA1c at the end of study showed -0.18% between treatment difference in favor of vildagliptin, p = .001. Mean body weight change at the end of study showed -0.68 kg between treatment difference in favor of vildagliptin, p < .001. Treatment exposure and adherence were high and similar in both cohorts. There were 4.3% adverse events reported in vildagliptin compared to 25.3% in the SU cohort, with hypoglycemia being the most experienced event in both cohorts. LIMITATIONS: Being observational and not mandating HE confirmation with blood glucose measurement (though it was done in a large number of patients) were key limitations. CONCLUSION: Anti-hyperglycemic treatment with vildagliptin led to significantly fewer hypoglycemia events compared to sulfonylurea treatment among Muslim diabetic patients who fast during Ramadan. Good glycemic control, weight control and safety results supported this outcome. PMID- 27684470 TI - What's in a name? Intolerance of uncertainty, other uncertainty-relevant constructs, and their differential relations to worry and generalized anxiety disorder. AB - A number of studies have examined the association of intolerance of uncertainty (IU) to trait worry and generalized anxiety disorder (GAD). However, few studies have examined the extent of overlap between IU and other psychological constructs that bear conceptual resemblance to IU, despite the fact that IU-type constructs have been discussed and examined extensively within psychology and other disciplines. The present study investigated (1) the associations of IU, trait worry, and GAD status to a negative risk orientation, trait curiosity, indecisiveness, perceived constraints, self-oriented and socially prescribed perfectionism, intolerance of ambiguity, the need for predictability, and the need for order and structure and (2) whether IU is a unique correlate of trait worry and of the presence versus absence of Probable GAD, when overlap with other uncertainty-relevant constructs is accounted for. N = 255 adults completed self report measures of the aforementioned constructs. Each of the constructs was significantly associated with IU. Only IU, and a subset of the other uncertainty relevant constructs were correlated with trait worry or distinguished the Probable GAD group from the Non-GAD group. IU was the strongest unique correlate of trait worry and of the presence versus absence of Probable GAD. Indecisiveness, self-oriented perfectionism and the need for predictability were also unique correlates of trait worry or GAD status. Implications of the findings are discussed, in particular as they pertain to the definition, conceptualization, and cognitive-behavioral treatment of IU in GAD. PMID- 27684471 TI - Effects of dietary methionine on performance, egg quality and glutathione redox system in egg-laying ducks. AB - In this study, 6 dietary DL-methionine (Met) levels (2.5, 3.0, 3.5, 4.0, 4.5 and 5.0 g/kg) were tested to estimate the dietary Met requirements of Longyan ducks from 19 to 46 weeks of age, and to investigate its effect on the glutathione redox system. In total, 1080 Longyan ducks aged 19 weeks were allocated randomly to the 6 dietary treatments, where each treatment comprised 6 replicate pens with 30 ducks per pen. Met had no effects on egg production, yolk weight, yolk colour or the glutathione redox system, but the egg weight, egg mass and feed conversion ratio (FCR) were improved significantly by dietary Met supplementation. As the dietary Met concentration increased, the eggshell thickness and breaking strength decreased significantly, whereas the albumen weight increased significantly. According to broken-line regression analysis, the optimum Met requirements for egg weight, egg mass, FCR and albumen weight are 686, 661, 658 and 731 mg/bird/d, respectively, with a dietary crude protein level of 170 g/kg. PMID- 27684473 TI - Alarmin high mobility group box-1 in maternal serum as a potential biomarker of chorioamnionitis-associated preterm birth. AB - Chorioamnionitis is associated with an increased risk of spontaneous preterm birth. The aim of this study was to investigate the serum levels of high mobility group box-1 (HMGB1) in pregnancies with histological chorioamnionitis (HCA) associated preterm labor (PTL) with intact membranes or preterm premature rupture of membranes (PPROM), and to access the role of serum HMGB1 in HCA and HCA associated PTL. A total of 190 pregnant women were enrolled in this study: PLT patients with (n = 28) or without HCA (n = 36), PPROM patients with (n = 26) or without HCA (n = 65), and non-HCA PTL controls (n = 35). Maternal serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay. Serum HMGB1 levels were significantly higher in PTL or PPROM patients than in control group (p < 0.01, respectively). The PPROM patients also exhibited higher serum HMGB1 levels compared to PTL patients (p = 0.015). HCA patients were characterized by significantly increased levels of serum HMGB1 when compared with non-HCA patients (p < 0.01). Therefore, maternal serum HMGB1 may become a potential biomarker of HCA and HCA-associated PTL. PMID- 27684474 TI - A pragmatic implementation of a 6-day physiotherapy service in a mixed inpatient rehabilitation unit. AB - PURPOSE: This study determined the impact of a pragmatic 6-day physiotherapy service on length of stay, functional independence, gait and balance in people undergoing inpatient rehabilitation, compared to a 5-day service. METHOD: A prospective cohort study with historical comparison was undertaken in a mixed inpatient rehabilitation unit. Intervention period participants (2011) meeting inclusion criteria were eligible for a 6-day physiotherapy service. All other participants, including the historical cohort (2010) received usual care (5-day physiotherapy). Length of stay, functional independence, gait and balance performance were measured. RESULTS: A total of 536 individuals participated in this study; 270 in 2011 (60% received 6-day physiotherapy) and 266 in 2010. Participants in 2011 showed a trend for reduced length of stay (1.7 days, 95%CI 0.53 to 3.92) compared to 2010. Other measures showed no significant differences between cohorts. In 2011, those receiving 6-day physiotherapy were more dependent, but showed significantly improved functional independence and balance compared to those receiving 5-day physiotherapy (p < 0.040) without impacting length of stay. CONCLUSION: Implementing a 6-day physiotherapy service in a "real world" rehabilitation setting demonstrated a trend towards reduced length of stay, and improved functional gains. This service could lead to cost-savings for hospitals and improved patient flow. Implications for Rehabilitation "Real-world" implementation of a 6-day physiotherapy service in rehabilitation shows a trend for reducing length of stay. This reduction in length of stay may lead to cost savings for the hospital system, and improve patient flow into rehabilitation. Patients receiving 6-day physiotherapy made significant gains in balance and functional independence compared to patients receiving 5-day physiotherapy services in the rehabilitation setting. PMID- 27684472 TI - Genomic Analysis Reveals Novel Diversity among the 1976 Philadelphia Legionnaires' Disease Outbreak Isolates and Additional ST36 Strains. AB - Legionella pneumophila was first recognized as a cause of severe and potentially fatal pneumonia during a large-scale outbreak of Legionnaires' disease (LD) at a Pennsylvania veterans' convention in Philadelphia, 1976. The ensuing investigation and recovery of four clinical isolates launched the fields of Legionella epidemiology and scientific research. Only one of the original isolates, "Philadelphia-1", has been widely distributed or extensively studied. Here we describe the whole-genome sequencing (WGS), complete assembly, and comparative analysis of all Philadelphia LD strains recovered from that investigation, along with L. pneumophila isolates sharing the Philadelphia sequence type (ST36). Analyses revealed that the 1976 outbreak was due to multiple serogroup 1 strains within the same genetic lineage, differentiated by an actively mobilized, self-replicating episome that is shared with L. pneumophila str. Paris, and two large, horizontally-transferred genomic loci, among other polymorphisms. We also found a completely unassociated ST36 strain that displayed remarkable genetic similarity to the historical Philadelphia isolates. This similar strain implies the presence of a potential clonal population, and suggests important implications may exist for considering epidemiological context when interpreting phylogenetic relationships among outbreak-associated isolates. Additional extensive archival research identified the Philadelphia isolate associated with a non-Legionnaire case of "Broad Street pneumonia", and provided new historical and genetic insights into the 1976 epidemic. This retrospective analysis has underscored the utility of fully assembled WGS data for Legionella outbreak investigations, highlighting the increased resolution that comes from long-read sequencing and a sequence type matched genomic data set. PMID- 27684476 TI - Relationship between Healthy Lifestyle and Sociodemographic Factors in Adolescents in Catalonia: Application of VISA-TEEN Questionnaire. AB - INTRODUCTION: There is a clear relationship between the way of life and the health of individuals, and therefore, we can speak of healthy and unhealthy lifestyles. There are different surveys and questionnaires that evaluate the lifestyles of adolescents, but none of them offers a final score that can quantify the healthfulness of an adolescent's lifestyle. It was with this goal that the VISA-TEEN questionnaire is developed and validated. The objective of this study is to apply the questionnaire to a sample of adolescents who attend school in Catalonia to evaluate the healthfulness of their lifestyles and to relate the scores obtained to different sociodemographic variables. METHODS: Cross-sectional study. A total of 2,832 students from 25 schools in Catalonia responded to the questionnaire. A descriptive analysis was performed, calculating the mean (Standard deviation), median (p25, p75), and confidence interval. The results were calculated for the total population, factoring according to gender, age, urban/rural population, origin (native/immigrant), and family wealth, which was based on the Family Affluence Scale (FAS II). The significance of the difference was calculated for each factor with the appropriate statistical test. RESULTS: For the total score of healthy lifestyle, the youngest students and those with the highest family wealth obtained higher scores. With respect to eating habits, girls scored higher than boys, and higher scores were observed in natives and those with high family wealth. For physical activity, boys scored higher, as well as younger individuals, natives, and those from rural areas. With respect to substance abuse, the worst scores were found in older individuals, students from rural areas, and natives. The rational use of leisure technology was only associated with age (worsening scores with older age). Lastly, hygiene was better with girls, decreased with age, and was worse with natives than immigrants. PMID- 27684477 TI - Exome Sequencing and Prediction of Long-Term Kidney Allograft Function. AB - Current strategies to improve graft outcome following kidney transplantation consider information at the human leukocyte antigen (HLA) loci. Cell surface antigens, in addition to HLA, may serve as the stimuli as well as the targets for the anti-allograft immune response and influence long-term graft outcomes. We therefore performed exome sequencing of DNA from kidney graft recipients and their living donors and estimated all possible cell surface antigens mismatches for a given donor/recipient pair by computing the number of amino acid mismatches in trans-membrane proteins. We designated this tally as the allogenomics mismatch score (AMS). We examined the association between the AMS and post-transplant estimated glomerular filtration rate (eGFR) using mixed models, considering transplants from three independent cohorts (a total of 53 donor-recipient pairs, 106 exomes, and 239 eGFR measurements). We found that the AMS has a significant effect on eGFR (mixed model, effect size across the entire range of the score: 19.4 [-37.7, -1.1], P = 0.0042, chi2 = 8.1919, d.f. = 1) that is independent of the HLA-A, B, DR matching, donor age, and time post-transplantation. The AMS effect is consistent across the three independent cohorts studied and similar to the strong effect size of donor age. Taken together, these results show that the AMS, a novel tool to quantify amino acid mismatches in trans-membrane proteins in individual donor/recipient pair, is a strong, robust predictor of long-term graft function in kidney transplant recipients. PMID- 27684478 TI - Single Plant Derived Nanotechnology for Synergistic Antibacterial Therapies. AB - Multiple new approaches to tackle multidrug resistant infections are urgently needed and under evaluation. One nanotechnology-based approach to delivering new relevant therapeutics involves silicon accumulator plants serving as a viable silicon source in green routes for the fabrication of the nanoscale drug delivery carrier porous silicon (pSi). If the selected plant leaf components contain medicinally-active species as well, then a single substance can provide not only the nanoscale high surface area drug delivery carrier, but the drug itself. With this idea in mind, porous silicon was fabricated from joints of the silicon accumulator plant Bambuseae (Tabasheer) and loaded with an antibacterial extract originating from leaves of the same type of plant (Bambuseae arundinacea). Preparation of porous silicon from Tabasheer includes extraction of biogenic silica from the ground plant by calcination, followed by reduction with magnesium in the presence of sodium chloride, thereby acting as a thermal moderator that helps to retain the mesoporous structure of the feedstock. The purified product was characterized by a combination of scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), and low temperature nitrogen gas adsorption measurements. Antimicrobial activity and minimum inhibitory concentration of a leaf extract of Bambuseae arundinacea was tested against the bacteria Escherichia Coli (E. Coli) and Staphylococcus aureus (S. Aureus), along with the fungus Candida albicans (C. Albicans). A S. aureus active ethanolic leaf extract was loaded into the above Tabasheer-derived porous silicon. Initial studies indicate sustained in vitro antibacterial activity of the extract-loaded plant derived pSi (25 wt %, TGA), as measured by disk diffusion inhibitory zone assays. Subsequent chromatographic separation of this extract revealed that the active antimicrobial species present include stigmasterol and 2,6-dimethoxy-p benzoquinone. PMID- 27684475 TI - Cell-Free Systems Based on CHO Cell Lysates: Optimization Strategies, Synthesis of "Difficult-to-Express" Proteins and Future Perspectives. AB - Nowadays, biotechnological processes play a pivotal role in target protein production. In this context, Chinese Hamster Ovary (CHO) cells are one of the most prominent cell lines for the expression of recombinant proteins and revealed as a safe host for nearly 40 years. Nevertheless, the major bottleneck of common in vivo protein expression platforms becomes obvious when looking at the production of so called "difficult-to-express" proteins. This class of proteins comprises in particular several ion channels and multipass membrane proteins as well as cytotoxic proteins. To enhance the production of "difficult-to-express" proteins, alternative technologies were developed, mainly based on translationally active cell lysates. These so called "cell-free" protein synthesis systems enable an efficient production of different classes of proteins. Eukaryotic cell-free systems harboring endogenous microsomal structures for the synthesis of functional membrane proteins and posttranslationally modified proteins are of particular interest for future applications. Therefore, we present current developments in cell-free protein synthesis based on translationally active CHO cell extracts, underlining the high potential of this platform. We present novel results highlighting the optimization of protein yields, the synthesis of various "difficult-to-express" proteins and the cotranslational incorporation of non-standard amino acids, which was exemplarily demonstrated by residue specific labeling of the glycoprotein Erythropoietin and the multimeric membrane protein KCSA. PMID- 27684479 TI - Spatial Variations of the Methanogenic Communities in the Sediments of Tropical Mangroves. AB - Methane production by methanogens in mangrove sediments is known to contribute significantly to global warming, but studies on the shift of methanogenic community in response to anthropogenic contaminations were still limited. In this study, the effect of anthropogenic activities in the mangrove sediments along the north and south coastlines of Singapore were investigated by pyrosequencing of the mcrA gene. Our results showed that hydrogenotrophic, acetoclastic and methylotrophic methanogens coexist in the sediments. The predominance of the methylotrophic Methanosarcinales reflects the potential for high methane production as well as the possible availability of low acetate and high methylated C-1 compounds as substrates. A decline in the number of acetoclastic/methylotrophic methanogens in favor of hydrogenotrophic methanogens was observed along a vertical profile in Sungei Changi, which was contaminated by heavy metals. The diversity of methanogens in the various contaminated stations was significantly different from that in a pristine St. John's Island. The spatial variation in the methanogenic communities among the different stations was more distinct than those along the vertical profiles at each station. We suggest that the overall heterogeneity of the methanogenic communities residing in the tropical mangrove sediments might be due to the accumulated effects of temperature and concentrations of nitrate, cobalt, and nickel. PMID- 27684480 TI - Responsive upper limb and cognitive fatigue measures during light precision work: an 8-hour simulated micro-pipetting study. AB - Many contemporary occupations are characterised by long periods of low loads. These lower force levels, which are relevant to the development of work-related musculoskeletal disorders, are usually not the focus of fatigue studies. In studies that did measure fatigue in light manual or precision work, within and between measurement responses were inconsistent. The aim of this study was to identify fatigue measures that were responsive at lower force levels (<10% MVC) over the course of an 8-h period. A complementary set of fatigue measures, reflecting both neuromuscular and cognitive mechanisms, was measured during a light precision micro-pipetting task performed by 11 participants. Nine measures were found to be significantly responsive over the 8-h period, including: ratings of perceived fatigue, postural tremor, blink frequency and critical flicker fusion frequency threshold. Common field measures, specifically electromyography RMS amplitude and maximum voluntary contractions, did not lead to extraordinary time effects. Practitioner summary: The findings provide insight towards the responsiveness of a complementary set of field usable fatigue measures at low work intensities Although commonly used measures did not reveal significant increases in fatigue, nine alternative measures were significantly responsive over the 8-h period. PMID- 27684482 TI - Feed presentation options in Swine early fattening mitigates Salmonella shedding and specifically modulates the faecal microbiota. AB - AIMS: The object of this study was to determine the impact of only modifying the processing and/or particle size of pig feed on Salmonella shedding and faecal microbiota. METHODS AND RESULTS: Pigs were fed a diet that varied only by their processing (pellet or mash) and their particle size (500, 750 or 1250 MUm) for 21 days. Salmonella detection in faeces and seroconversion were determined. Faecal microbiota was assessed by Ion Torrent amplicon sequencing and real-time PCR. Significantly fewer pigs (P < 0.05) shed Salmonella in the groups fed mash 500 (1) and mash or pellet 1250 (5 each) compared to the commercial reference group (15) fed pellet 500. Both mash processing and large particle size raised the proportion and number of bacteria from the Bifidobacterium genus in the faecal microbiota of the pigs. Thirteen other taxa significantly varied (P < 0.0005) with feed presentation. CONCLUSION: Mash processing and/or large particle size in pig feed reduces Salmonella shedding prevalence and promotes beneficial populations of digestive microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to demonstrate a difference in Salmonella shedding through only modifying pig feed presentation and is the first to extensively describe modifications of faecal microbiota. PMID- 27684483 TI - 24-month durability after crossover to the prostatic urethral lift from randomised, blinded sham. AB - OBJECTIVE: To evaluate the 24-month effectiveness of the prostatic urethral lift (PUL) procedure in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) assessed through a crossover study. PATIENTS AND METHODS: In all, 53 patients underwent a sham procedure as part of the blinded, randomised L.I.F.T. (Luminal Improvement Following prostatic Tissue approximation for the treatment of LUTS secondary to BPH) study at 19 centres and elected to enrol in this crossover study. The crossover procedure involved placement of permanent implants (UroLift(r) system) into the prostatic lateral lobes. Patients were followed for 3 months after the sham procedure and then for 24 months after crossover to PUL, with assessments of urinary symptom relief, quality of life (QoL), urinary flow rate, sexual function, and adverse events. RESULTS: At 24 months after crossover to PUL, the International Prostate Symptom Score (IPSS), QoL, BPH Impact Index, and maximum urinary flow rate improved 36%, 40%, 54%, and 77% from baseline, respectively. Each IPSS parameter on average improved significantly from baseline (P < 0.005) and remained stable throughout follow-up. Symptom response after the sham procedure indicated initial improvement at 1 month with significant decay by 3 months. Adverse events were typically mild to moderate and patients returned rapidly to normal activity. Four patients (8%) required intervention with transurethral resection of the prostate and one patient required additional PUL implants within the 24-month period. There were no reported instances of de novo sustained erectile or ejaculatory dysfunction. CONCLUSIONS: The PUL procedure is associated with rapid symptom relief, increased urinary flow rate and QoL improvement that remain stable over 24 months. Morbidity is low and sexual function is preserved. PMID- 27684484 TI - Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical. AB - Dietary isothiocyanates abundant as glucosinolate precursors in many edible cruciferous vegetables are effective for prevention of cancer in chemically induced and transgenic rodent models. Some of these agents, including phenethyl isothiocyanate (PEITC), have already advanced to clinical investigations. The primary route of isothiocyanate metabolism is its conjugation with glutathione (GSH), a reaction catalyzed by glutathione S-transferase (GST). The pi class GST of subunit type 1 (hGSTP1) is much more effective than the alpha class GST of subunit type 1 (hGSTA1) in catalyzing the conjugation. Here, we report the crystal structures of hGSTP1 and hGSTA1 each in complex with the GSH adduct of PEITC. We find that PEITC also covalently modifies the cysteine side chains of GST, which irreversibly inhibits enzymatic activity. PMID- 27684485 TI - Incidence of underlying congenital cholesteatoma in 28 patients with persistent unilateral otitis media with effusion. PMID- 27684481 TI - Quantitative Proteomics of Sleep-Deprived Mouse Brains Reveals Global Changes in Mitochondrial Proteins. AB - Sleep is a ubiquitous, tightly regulated, and evolutionarily conserved behavior observed in almost all animals. Prolonged sleep deprivation can be fatal, indicating that sleep is a physiological necessity. However, little is known about its core function. To gain insight into this mystery, we used advanced quantitative proteomics technology to survey the global changes in brain protein abundance. Aiming to gain a comprehensive profile, our proteomics workflow included filter-aided sample preparation (FASP), which increased the coverage of membrane proteins; tandem mass tag (TMT) labeling, for relative quantitation; and high resolution, high mass accuracy, high throughput mass spectrometry (MS). In total, we obtained the relative abundance ratios of 9888 proteins encoded by 6070 genes. Interestingly, we observed significant enrichment for mitochondrial proteins among the differentially expressed proteins. This finding suggests that sleep deprivation strongly affects signaling pathways that govern either energy metabolism or responses to mitochondrial stress. Additionally, the differentially expressed proteins are enriched in pathways implicated in age-dependent neurodegenerative diseases, including Parkinson's, Huntington's, and Alzheimer's, hinting at possible connections between sleep loss, mitochondrial stress, and neurodegeneration. PMID- 27684487 TI - US long-haul truck driver work organization and the association with cardiometabolic disease risk. AB - Work organization, including long working hours, irregular work schedules, and job stress, has been associated with increased cardiometabolic disease (CMD) risk for numerous working populations. The purpose of this study was to examine the associations between work hours, work schedules, job stress, and CMD risk for a sample of US long-haul truck drivers (LHTDs). A nonexperimental, descriptive, cross-sectional design was employed to collect survey and anthropometric data from 260 US LHTDs at a major truck stop. The mean BMI was 33.40 kg/m2 and mean waist circumference was 114.77 cm. Using logistic regression, researchers found longer work hours, especially greater than 11 hours daily, were associated with increased odds for an extremely high risk of CMD. Results support comprehensive and integrated approaches that address work organization, and in particular long working hours, to reduce drivers' CMD risk. PMID- 27684486 TI - Arg126 and Asp49 Are Essential for the Catalytic Function of Microsomal Prostaglandin E2 Synthase 1 and Ser127 Is Not. AB - INTRODUCTION: Prostaglandins are signaling molecules that regulate different physiological processes, involving allergic and inflammatory responses and cardiovascular control. They are involved in several pathophysiological processes, including inflammation and cancer. The inducible terminal enzyme, microsomal prostaglandin E synthase 1 (MPGES1), catalyses prostaglandin E2 production during inflammation. MPGES1 has therefore been intensively studied as a pharmaceutical target and many competitive inhibitors targeting its active site have been developed. However, little is known about its catalytic mechanism. AIM: The objective of this study was to investigate which amino acids play a key role in the catalytic mechanism of MPGES1. MATERIALS AND METHODS: Based on results and predictions from previous structural studies, the amino acid residues Asp49, Arg73, Arg126, and Ser127 were chosen and altered by site-directed mutagenesis. The mutated enzyme variants were cloned and expressed in both the E. coli and the Baculovirus expression systems. Their catalytic significance was evaluated by activity measurements with prostanoid profiling. RESULTS AND CONCLUSIONS: Our study shows that Arg126 and Asp49 are absolutely required for the catalytic activity of MPGES1, as when exchanged, the enzyme variants loose activity. Ser127 and Arg73 on the other hand, don't seem to be central to the catalytic mechanism because when exchanged, their variants retain considerable activity. Our finding that the Ser127Ala variant retains activity was surprising since high-resolution structural data supported a role in glutathione activation. The close proximity of Ser127 to the active site is, however, supported since the Ser127Cys variant displays 80% lowered activity. PMID- 27684488 TI - Infective endocarditis in haemodialysis patients: lower complications and same mortality rate as in non-haemodialysis patients. PMID- 27684490 TI - Immunotoxicological Evaluation of Genetically Modified Rice Expressing Cry1Ab/Ac Protein (TT51-1) by a 6-Month Feeding Study on Cynomolgus Monkeys. AB - The present study was performed to evaluate the food safety of TT51-1, a new type of genetically modified rice that expresses the Cry1Ab/Ac protein (Bt toxin) and is highly resistant to most lepidopteran pests. Sixteen male and 16 female cynomolgus monkeys were randomly divided into four groups: conventional rice (non genetically modified rice, non-GM rice), positive control, 17.5% genetically modified rice (GM rice) and 70% GM rice. Monkeys in the non-GM rice, positive control, and GM rice groups were fed on diets containing 70% non-GM rice, 17.5% GM rice or 70% GM rice, respectively, for 182 days, whereas animals in the positive group were intravenously injected with cyclophosphamide every other day for a total of four injections before the last treatment. Six months of treatment did not yield abnormal observations. Specifically, the following parameters did not significantly differ between the non-GM rice group and GM rice groups: body weight, food consumption, electrocardiogram, hematology, immuno-phenotyping of lymphocytes in the peripheral blood, mitogen-induced peripheral blood lymphocyte proliferation, splenocyte proliferation, KLH-T cell-dependent antibody response, organ weights and ratios, and histological appearance (p>0.05). Animals from the GM rice group differed from animals in the non-GM rice group (p<0.05) in several parameters: specifically, their body temperatures and serum alanine aminotransferase (ALT) levels were higher, whereas their levels of serum K+, Cl- and cytokines (IL-2, IL-4 and IL-5) were lower. Because dose- or time-dependent changes were not observed in this study and animals appeared histologically normal, the aforementioned differences were not considered to be adverse or related to the treatment with GM rice. In conclusion, a 6-month feeding study of TT51-1 did not show adverse immunotoxicological effects on cynomolgus monkeys. PMID- 27684491 TI - Adherence to Treatment and Factors Affecting Adherence of Epileptic Patients at Yirgalem General Hospital, Southern Ethiopia: A Prospective Cross-Sectional Study. AB - BACKGROUND: Non adherence of epileptic patients to antiepileptic medication often leads to an increased risk of seizures and worsening of disease, death and increased health care costs. OBJECTIVE: to assess adherence to treatment and factors affecting adherence of epileptic patients at Yirgalem General Hospital, Southern Ethiopia. METHODS AND MATERIALS: We conducted a cross-sectional study on epileptic patients from February 9 to 22, 2015. Data were collected from patients >=18 years old. Adherence was measured using the eight-item Morisky's medication adherence scale. All consecutive patients coming to epilepsy clinic during the study period were interviewed until the calculated sample size (210) was obtained. We collected patient demographics, perception about epilepsy and adherence to medication(s). We used chi-square tests and a binary logistic regression model for statistical analysis. Statistical significance was considered at P<0.05. RESULTS: out of a total of 210 participants, 194 were willing to participate and were studied. Of the 194 participants, 109 (56.2%) were males. The mean age of the participants was 33.62+/-11.44 years; range 18 to 66 years. The majority, 123(63.41%), of the participants were taking two antiepileptic medications. Sixty two (32%) of the participants were adherent to their treatment. The most common reported reasons for non-adherence were forgetfulness 49(75.4%) and run out of pills 7(10.8%). Factors that affect medication adherence are epilepsy treatment for <1 year (P = 0.011), epilepsy treatment for 1-3 years (P = 0.002), epilepsy treatment for 3-5 years (P = 0.007), being married (P = 0.006), grade 9-12 education (P = 0.028), college or university education (P = 0.002) and absence of co-morbidity (P = 0.008). CONCLUSIONS: The rate of adherence observed in this study was low. The most common reason for non- adherence was forgetfulness. Therefore, the hospital should devise strategies to improve adherence of epileptic patients at the hospital. PMID- 27684492 TI - Pregabalin for pain in fibromyalgia in adults. AB - BACKGROUND: This review updates part of an earlier Cochrane review on 'Pregabalin for acute and chronic pain in adults' (Moore 2009), and considers only fibromyalgia pain.Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is an antiepileptic drug also used in management of chronic pain conditions, including fibromyalgia. Pain response with pregabalin is associated with major benefits for other symptoms, and improved quality of life and function in people with chronic painful conditions. OBJECTIVES: To assess the analgesic efficacy and adverse events of pregabalin for pain in fibromyalgia in adults, compared with placebo or any active comparator. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE for randomised controlled trials from inception to May 2009 for the original review and to 16 March 2016 for this update. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. SELECTION CRITERIA: We included randomised, double-blind trials of eight weeks' duration or longer, comparing pregabalin with placebo or another active treatment for relief of pain in fibromyalgia, and reporting on the analgesic effect of pregabalin, with subjective pain assessment by the participant. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with moderate pain relief (at least 30% pain relief over baseline or much or very much improved on Patient Global Impression of Change scale (PGIC)) or substantial pain relief (at least 50% pain relief over baseline or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and number needed to treat (NNT), using standard methods. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. MAIN RESULTS: Our searches identified two new published studies with classic design, and one new published study with an enriched enrolment randomised withdrawal (EERW) design.We included eight studies. Five (3283 participants) had a classic design in which participants were randomised at the start of the study to pregabalin (150, 300, 450, or 600 mg daily) or placebo, with assessment after 8 to 13 weeks of stable treatment. No studies included active comparators. Studies had low risk of bias, except that the last observation carried forward (LOCF) imputation method used in analyses of the primary outcomes could overestimate treatment effect.Pregabalin increased the number of participants experiencing substantial benefit (at least 50% pain intensity reduction after 12 or 13 weeks' stable treatment (450 mg: RR 1.8, 95% CI 1.4 to 2.1, 1874 participants, 5 studies, high quality evidence)). Substantial benefit with pregabalin 300 to 600 mg was experienced by about 14% of participants with placebo, but about 9% more with pregabalin 300 to 600 mg (22% to 24%) (high quality evidence). Pregabalin increased the number of participants experiencing moderate benefit (at least 30% pain intensity reduction after 12 or 13 weeks' stable treatment) (450 mg: RR 1.5, 95% CI (1.3 to 1.7), 1874 participants, 5 studies, high quality evidence). Moderate benefit with pregabalin 300 to 600 mg was experienced by about 28% of participants with placebo, but about 11% more with pregabalin 300 to 600 mg (39% to 43%) (high quality evidence). A similar magnitude of effect was found using PGIC of 'very much improved' and 'much or very much improved'. NNTs for these outcomes ranged between 7 and 14 (high quality evidence).A small study (177 participants) compared nightly with twice-daily pregabalin, and concluded there was no difference in effect.Two studies (1492 participants began initial dose titration, 687 participants randomised) had an EERW design in which those with good pain relief after titration were randomised, double blind, to continuing the effective dose (300 to 600 mg pregabalin daily) or a short down-titration to placebo for 13 or 26 weeks. We calculated the outcome of maintained therapeutic response (MTR) without withdrawal, equivalent to a moderate benefit. Of those randomised, 40% had MTR with pregabalin and 20% with placebo (high quality evidence). The NNT was 5, but normalised to the starting population tested it was 12. About 10% of the initial population would have achieved the MTR outcome, similar to the result from studies of classic design. MTR had no imputation concerns.The majority (70% to 90%) of participants in all treatment groups experienced adverse events. Specific adverse events were more common with pregabalin than placebo, in particular dizziness, somnolence, weight gain, and peripheral oedema, with number needed to harm of 3.7, 7.4, 18, and 19 respectively for all doses combined (high quality evidence). Serious adverse events did not differ between active treatment groups and placebo (very low quality evidence). Withdrawals for any reason were more common with pregabalin than placebo only with the 600 mg dose in studies of classic design. Withdrawals due to adverse events were about 10% higher with pregabalin than placebo, but withdrawals due to lack of efficacy were about 6% lower (high quality evidence). AUTHORS' CONCLUSIONS: Pregabalin 300 to 600 mg produces a major reduction in pain intensity over 12 to 26 weeks with tolerable adverse events for a small proportion of people (about 10% more than placebo) with moderate or severe pain due to fibromyalgia. The degree of pain relief is known to be accompanied by improvements in other symptoms, quality of life, and function. These results are similar to other effective medicines in fibromyalgia (milnacipran, duloxetine). PMID- 27684489 TI - Immunoproteomic analysis of house dust mite antigens reveals distinct classes of dominant T cell antigens according to function and serological reactivity. AB - BACKGROUND: House dust mite (HDM) allergens are a common cause of allergy and allergic asthma. A comprehensive analysis of proteins targeted by T cells, which are implicated in the development and regulation of allergic disease independent of their antibody reactivity, is still lacking. OBJECTIVE: To comprehensively analyse the HDM-derived protein targets of T cell responses in HDM-allergic individuals, and investigate their correlation with IgE/IgG responses and protein function. METHODS: Proteomic analysis (liquid chromatography-tandem mass spectrometry) of HDM extracts identified 90 distinct protein clusters, corresponding to 29 known allergens and 61 novel proteins. Peripheral blood mononuclear cells (PBMC) from 20 HDM-allergic individuals were stimulated with HDM extracts and assayed with a set of ~2500 peptides derived from these 90 protein clusters and predicted to bind the most common HLA class II types. 2D immunoblots were made in parallel to elucidate IgE and IgG reactivity, and putative function analyses were performed in silico according to Gene Ontology annotations. RESULTS: Analysis of T cell reactivity revealed a large number of T cell epitopes. Overall response magnitude and frequency was comparable for known and novel proteins, with 15 antigens (nine of which were novel) dominating the total T cell response. Most of the known allergens that were dominant at the T cell level were also IgE reactive, as expected, while few novel dominant T cell antigens were IgE reactive. Among known allergens, hydrolase activity and detectable IgE/IgG reactivity are strongly correlated, while no protein function correlates with immunogenicity of novel proteins. A total of 106 epitopes accounted for half of the total T cell response, underlining the heterogeneity of T cell responses to HDM allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Herein, we define the T cell targets for both known allergens and novel proteins, which may inform future diagnostics and immunotherapeutics for allergy to HDM. PMID- 27684494 TI - Triggering of apoptosis in osteosarcoma cells by graphene/single-walled carbon nanotube hybrids via the ROS-mediated mitochondrial pathway. AB - Carbon nanomaterials are increasingly significant in the biological and medical fields, especially becoming promising candidates in treating difficult and complicated disease. Graphene/single-walled carbon nanotubes (G/SWCNT) hybrids is 3D structure which has been constructed by combining 1D single-walled carbon nanotubes (SWCNTs) and 2D graphene. However, the effects of the nanomaterial on biological systems are limited. In this study, we report a systematic investigation of the cytotoxicity and in vivo biodistribution of G/SWCNT hybrids on osteosarcoma cells (HOS and U2OS). The CCK-8, neutral red, and lactic dehydrogenase assays demonstrated that the cytotoxicity of G/SWCNT hybrids exhibits a dose-dependent behavior on osteosarcoma cells. In our conditions, the hybrids were less cytotoxic than graphene and single-walled carbon nanotubes. The results also showed the apoptosis of osteosarcoma cells induced by G/SWCNT hybrids was through the increase of intracellular reactive oxygen species, the decrease of mitochondrial membrane potential, the alternation of apoptosis related proteins, and then triggered the ROS-mediated mitochondrial pathway. Moreover, the in vivo biodistribution of G/SWCNT hybrids was observed by histological analysis of major organs in mice, and showed that organs were neither damaged nor inflammatory. This study demonstrated that G/SWCNT hybrids could serve as a potential platform in anticancer therapy. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 443-453, 2017. PMID- 27684493 TI - Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells. AB - Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), which controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. The surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the observed effect of Corexit-EC9527A in the cell. PMID- 27684495 TI - Discourses of masculinity, femininity and sexuality in Uganda's Stand Proud, Get Circumcised campaign. AB - This paper analyses discourses of masculinity, femininity and sexuality in Stand Proud, Get Circumcised, a public health campaign promoting circumcision as an HIV prevention strategy in Uganda. The campaign includes posters highlighting the positive reactions of women to circumcised men, and is intended to support the national rollout of voluntary medical male circumcision. We offer a critical discourse analysis of representations of masculinity, femininity and sexuality in relation to HIV prevention. The campaign materials have a playful feel and, in contrast to ABC (Abstain, Be faithful, Use condoms) campaigns, acknowledge the potential for pre-marital and extra-marital sex. However, these posters exploit male anxieties about appearance and performance, drawing on hegemonic masculinity to promote circumcision as an idealised body aesthetic. Positioning women as the campaign's face reasserts a message that women are the custodians of family health and simultaneously perpetuates a norm of estrangement between men and their health. The wives' slogan, 'we have less chance of getting HIV', is misleading, because circumcision only directly prevents female-to-male HIV transmission. Reaffirming hegemonic notions of appearance- and performance-based heterosexual masculinity reproduces existing unsafe norms about masculinity, femininity and sexuality. In selling male circumcision, the posters fail to promote an overall HIV-prevention message. PMID- 27684497 TI - Anti-p200/laminin gamma1 pemphigoid associated with metastatic oesophageal cancer. PMID- 27684496 TI - Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus. AB - Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks' gestation. There was a statistically significant prevalence of the HHEX rs5015480 CC genotype and C allele among women with GDM (C vs T allele, p = 0.021, odds ratio OR = 1.40, 95% CI: 1.05-1.87). Statistically significant higher increase of body mass and BMI during pregnancy was found in women with the HHEX rs5015480 CC genotype. The results of our study suggest an association between the HHEX gene rs5015480 polymorphism and risk of GDM. The HHEX gene rs5015480 C allele may be a risk allele of GDM that is associated with increased BMI during pregnancy. PMID- 27684498 TI - Using Family-Based Exposure With Response Prevention to Treat Obsessive Compulsive Disorder in Young Children: A Case Study. AB - Cognitive-behavioral therapy (CBT) using exposure with response prevention (ERP) is the treatment of choice for obsessive-compulsive disorder (OCD); however, developmental modifications should be considered when treating young children. This article presents a case study illustrating family-based CBT using ERP with a 7-year-old boy. The delivery of ERP for this case was guided by 3 main principles: (a) family involvement with a focus on reducing family accommodation, (b) understanding the functional relation between the client's obsessions and compulsions, and (c) creating conditions to facilitate habituation during exposure. Outcomes for this case indicate significant improvement in functioning and OCD symptoms. Results highlight the importance of family involvement and the applicability of using a function-based habituation framework when delivering ERP to this unique population. PMID- 27684499 TI - Discrete capacity limits and neuroanatomical correlates of visual short-term memory for objects and spatial locations. AB - Working memory is responsible for keeping information in mind when it is no longer in view, linking perception with higher cognitive functions. Despite such crucial role, short-term maintenance of visual information is severely limited. Research suggests that capacity limits in visual short-term memory (VSTM) are correlated with sustained activity in distinct brain areas. Here, we investigated whether variability in the structure of the brain is reflected in individual differences of behavioral capacity estimates for spatial and object VSTM. Behavioral capacity estimates were calculated separately for spatial and object information using a novel adaptive staircase procedure and were found to be unrelated, supporting domain-specific VSTM capacity limits. Voxel-based morphometry (VBM) analyses revealed dissociable neuroanatomical correlates of spatial versus object VSTM. Interindividual variability in spatial VSTM was reflected in the gray matter density of the inferior parietal lobule. In contrast, object VSTM was reflected in the gray matter density of the left insula. These dissociable findings highlight the importance of considering domain specific estimates of VSTM capacity and point to the crucial brain regions that limit VSTM capacity for different types of visual information. Hum Brain Mapp 38:767-778, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27684500 TI - Frequency of Undetected Glove Perforation and Associated Risk Factors in Equine Surgery. AB - OBJECTIVE: To estimate the frequency of undetected perforations in surgical gloves during equine surgery and to identify risk factors associated with occurrence. STUDY DESIGN: Observational cohort study. SAMPLE POPULATION: Surgical gloves-292 pairs. METHODS: Water leak tests were performed on gloves after equine surgery to detect perforations. Fifty pairs of unused gloves were also tested. Potential risk factors were recorded. Logistic regression was used to explore associations between putative risk factors and perforation. RESULTS: No perforations were detected in the unused gloves. Of 292 pairs of used gloves tested, 80 (27%) had at least one glove perforation per pair. The frequency of perforations was not different between surgery diplomates and residents (P=.69). The length and type of surgery were significantly associated with the likelihood of undetected glove perforation with surgeries longer than 60 minutes approximately 2.5 times more likely to result in glove perforation (P=.005). Surgery classified as soft tissue, orthopedic or exploratory celiotomy was 3 times more likely to result in glove perforation than minimally invasive surgery. The perforations occurred significantly more frequently in the nondominant hand (19%) than the dominant hand (11%) (P=.009). CONCLUSION: There is a high occurrence of undetected glove perforation in equine surgery. Precautions can be suggested based on this study although further investigation is required to assess whether glove perforations are associated with surgical site infections. PMID- 27684501 TI - The practice of clinical neuropsychology in Australia. AB - OBJECTIVE: This paper describes the development and practice of clinical neuropsychology in Australia. METHOD: Clinical Neuropsychology has shown rapid growth in Australia over the past three decades. Comprehensive and specialized training programs are producing high quality graduates who are employed in a broad range of settings or private practice. RESULTS: Australia now has a substantial number of clinical neuropsychologists with specialist training. Whilst the majority of Australian clinical neuropsychologists still undertake assessment predominantly, there are growing opportunities for clinical neuropsychologists in rehabilitation and in a broad range of research contexts. Cultural issues relating to the assessment of Indigenous Australians and immigrants from many countries present significant challenges. Some major contributions have been made in the realms of test development and validation across various age groups. Australian clinical neuropsychologists are also contributing significantly to research in the fields of traumatic brain injury, aging and dementias, epilepsy, memory assessment, rehabilitation, substance abuse, and other psychiatric disorders. CONCLUSION: Expansion of roles of clinical neuropsychologists, in domains such as rehabilitation and research is seen as essential to underpin continuing growth of employment opportunities for the profession. PMID- 27684502 TI - Frequency of temporomandibular disorder signs and symptoms among call center employees. AB - OBJECTIVE: The current study aimed to investigate the frequency of signs and symptoms of temporomandibular disorders (TMD) among call center employees. METHODS: Workers from four call centers (CC) were invited to participate in this study. The examination was based on the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD). The tenderness of the masticator muscles was assessed on both sides by bilateral palpation. The mobility of the mandible was measured with a plastic millimeter ruler on opening, lateral excursions, and protrusion. RESULTS: In total, 124 call center employees with a mean age of 28.61 +/- 4.71 (between 22 and 47 years of age) were enrolled in this study. There was no statistically significant relation between the numbers of calls answered in a day and teeth clenching, teeth grinding, earache, tinnitus, or pain on yawning/chewing. Only protrusive movement pain and joint noise were significantly higher among employees who answered more than 140 calls/day (p < 0.01). An evaluation of the TMD signs and symptoms in relation to job stress level revealed that job stress level significantly affected the incidence of headaches among call center employees (p < 0.01). CONCLUSION: The present study demonstrated no statistically significant relation between TMD signs and symptoms and call center employees except protrusive movement pain and joint noise. This relation was seen only in the employees who answered more than 140 calls per day. Headache, teeth clenching, and TMJ noise were the signs and symptoms encountered most often in this study. Multicentered studies in different geographic locations should be conducted to eliminate the limitation of this study. PMID- 27684503 TI - Reply to letter to the editor. PMID- 27684504 TI - Risk profile and health vulnerability of female workers who pick cotton by organanochlorine pesticides from southern Punjab, Pakistan. AB - The present study was conducted to highlight the existing level of organochlorine pesticides (OCPs) from human milk (n = 45) and blood serum (n = 40) of female workers who pick cotton in Khanewal District, southern Punjab, Pakistan. Source apportionment, congener-specific analysis, and risk surveillance of OCPs are reported from human milk and blood samples. Levels of OCPs in milk and blood serum samples ranged from 15.7 ppb to 538.3 ppb and from 16.4 ppb to 747.1 ppb, respectively, and were lower than previously published reports from other regions of the globe. Congener-specific analysis revealed that DDTs were predominant, followed by hexachlorocyclohexane, chlordane, and hexachlorobenzene. Calculated results for source apportionment analysis suggested that contamination load was a new input of DDTs as well as the historic use of lindane in the study area. Levels of OCPs in milk and blood serum were significantly (p < 0.05) correlated with age, time period of picking cotton, and number of children. Health risk revealed that female workers had risk of cancer among 1 per million; however, noncarcinogenic risks were not considerable. Environ Toxicol Chem 2017;36:1193 1201. (c) 2016 SETAC. PMID- 27684505 TI - Turn up the lysosome. AB - Lysosomes are digestive organelles of the endocytic and autophagic pathways. Increasing lysosome enzyme activities could help to clear pathological cellular waste. A recent study shows that lysosomal digestive functions can be promoted in isolated cells and mice by pharmacologically stimulating the autophagy- and lysosome-regulating transcription factors TFEB and ZKSCAN3 through previously unrecognized mTORC1-independent pathways acting via PKC. PMID- 27684507 TI - Erratum: Sex hormones establish a reserve pool of adult muscle stem cells. PMID- 27684506 TI - Regional tumour glutamine supply affects chromatin and cell identity. AB - Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of alpha-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy-resistant state of the tumour cells. PMID- 27684508 TI - Prognostic value of sentinel lymph node biopsy in melanomas of different Breslow's thickness. AB - BACKGROUND: Although sentinel lymph node biopsy (SLNB) is the most sensitive and accurate investigative modality for establishing regional node status in patients with melanoma, its role and benefit in melanoma of different Breslow's thickness is still controversial. OBJECTIVE: The current study aimed mainly to evaluate the effects of SLNB results on important outcome parameters in primary melanomas with different Breslow's thicknesses. METHODS: In a retrospective cohort (1990 to 2014), all cases of single, primary localised cutaneous melanoma tumours were evaluated. Data collected consisted of tumour location, tumour type, ulceration, Breslow's thickness and SLNB result. In addition, locoregional recurrence, distant metastases, disease-free and overall survival were used as the important parameters to compare outcome among the various groups in the current study. RESULTS: A total of 1111 patients (527 female, 584 male; mean age 64.33 +/- 15.44 years) were considered in the analyses in this study, with mean follow-up of 22 77.3 days. The multivariate Cox analysis showed that age, ulceration, Breslow's depth and SLNB result significantly decreased disease-free survival. This analysis also demonstrated that age, gender, ulceration, Breslow's depth and SLNB result significantly affected overall survival. Furthermore, the Kaplan-Meier method showed that the patients with negative SLNB had longer disease-free survival than the patients with positive SLNB in thin, intermediate and thick melanomas (p <0.001, p <0.001 and p = 0.008, respectively). Additionally, in the patients with intermediate melanomas significant better overall survival outcome was observed in those with negative SLNB (p <0.001). Despite worse mean overall survival of the patients with thin or thick melanomas and positive SLNB compared with the patients with negative SLNB, this difference was not statistically significant (p = 0.077 and p = 0.13, respectively). CONCLUSION: Sentinel lymph node biopsy of melanomas provides important prognostic information and the outcome provides additional information for the management and treatment of the patient. PMID- 27684510 TI - A Fluorescence-based Assay of Phospholipid Scramblase Activity. AB - Scramblases translocate phospholipids across the membrane bilayer bidirectionally in an ATP-independent manner. The first scramblase to be identified and biochemically verified was opsin, the apoprotein of the photoreceptor rhodopsin. Rhodopsin is a G protein-coupled receptor localized in rod photoreceptor disc membranes of the retina where it is responsible for the perception of light. Rhodopsin's scramblase activity does not depend on its ligand 11-cis-retinal, i.e., the apoprotein opsin is also active as a scramblase. Although constitutive and regulated phospholipid scrambling play an important role in cell physiology, only a few phospholipid scramblases have been identified so far besides opsin. Here we describe a fluorescence-based assay of opsin's scramblase activity. Opsin is reconstituted into large unilamellar liposomes composed of phosphatidylcholine, phosphatidylglycerol and a trace quantity of fluorescent NBD labeled PC (1-palmitoyl-2-{6-[7-nitro-2-1,3-benzoxadiazole-4-yl)amino]hexanoyl} sn-glycero-3-phosphocholine). Scramblase activity is determined by measuring the extent to which NBD-PC molecules located in the inner leaflet of the vesicle are able to access the outer leaflet where their fluorescence is chemically eliminated by a reducing agent that cannot cross the membrane. The methods we describe have general applicability and can be used to identify and characterize scramblase activities of other membrane proteins. PMID- 27684512 TI - A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products. AB - The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist's toolbox. PMID- 27684514 TI - Preparation of alpha-Acyloxy Ketones via Visible-Light-Driven Aerobic Oxo Acyloxylation of Olefins with Carboxylic Acids. AB - We developed a visible-light driven oxo-acyloxylation of aryl alkenes with carboxylic acids and molecular oxygen. A metal-free photoredox system, consisting of an acridinium photocatalyst, an organic base, and molecular sieve (MS) 4 A, promotes chemoselective aerobic photooxidation of aryl alkenes. This approach may provide a green, practical, and metal-free protocol for a wide range of alpha acyloxy ketones. PMID- 27684513 TI - Direct Observation of a Dark State in the Photocycle of a Light-Driven Molecular Motor. AB - Controlling the excited-state properties of light driven molecular machines is crucial to achieving high efficiency and directed functionality. A key challenge in achieving control lies in unravelling the complex photodynamics and especially in identifying the role played by dark states. Here we use the structure sensitivity and high time resolution of UV-pump/IR-probe spectroscopy to build a detailed and comprehensive model of the structural evolution of light driven molecular rotors. The photodynamics of these chiral overcrowded alkene derivatives are determined by two close-lying excited electronic states. The potential energy landscape of these "bright" and "dark" states gives rise to a broad excited-state electronic absorption band over the entire mid-IR range that is probed for the first time and modeled by quantum mechanical calculations. The transient IR vibrational fingerprints observed in our studies allow for an unambiguous identification of the identity of the "dark" electronic excited state from which the photon's energy is converted into motion, and thereby pave the way for tuning the quantum yield of future molecular rotors based on this structural motif. PMID- 27684515 TI - Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling. AB - Identifying the molecular target(s) of small molecules is a challenging but necessary step towards understanding their mechanism of action. While several target identification methods have been developed and used to successfully elucidate the binding proteins of a variety of small molecules, these techniques have drawbacks that make them unsuitable for detecting certain types of small molecule-target interactions. In particular, non-covalent interactions that depend on native cellular conditions, such as those of membrane proteins whose structures may be perturbed upon cell lysis, are often not amenable to affinity based target identification methods. Here, we demonstrate a method wherein a probe containing a photolabile group is used to covalently crosslink to the small molecule binding protein within the environment of the live cell, allowing the detection and isolation of the target protein without the need for maintenance of the interaction after cell lysis. This technique is a valuable tool for studying biologically interesting small molecules with unknown mechanisms, both in the context of basic biology as well as drug discovery. PMID- 27684511 TI - Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline. AB - RATIONALE: Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically indicated lung biopsy specimens obtained during a period of persistent decline. OBJECTIVES: To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy. METHODS: Six adolescents with CF (mean age, 16.2 y; mean FEV1, 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV1 decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-beta (TGF-beta, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and alpha-smooth muscle actin (to identify myofibroblasts). MEASUREMENTS AND MAIN RESULTS: All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-beta-dependent process) was prominent in specimens with significant airway remodeling. CONCLUSIONS: Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-beta-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease. PMID- 27684516 TI - Improved Polymerase Chain Reaction-restriction Fragment Length Polymorphism Genotyping of Toxic Pufferfish by Liquid Chromatography/Mass Spectrometry. AB - An improved version of a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method for genotyping toxic pufferfish species by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) is described. DNA extraction is carried out using a silica membrane-based DNA extraction kit. After the PCR amplification using a detergent-free PCR buffer, restriction enzymes are added to the solution without purifying the reaction solution. A reverse-phase silica monolith column and a Fourier transform high resolution mass spectrometer having a modified Kingdon trap analyzer are employed for separation and detection, respectively. The mobile phase, consisting of 400 mM 1,1,1,3,3,3-hexafluoro-2-propanol, 15 mM triethylamine (pH 7.9) and methanol, is delivered at a flow rate of 0.4 ml/min. The cycle time for LC/ESI-MS analysis is 8 min including equilibration of the column. Deconvolution software having an isotope distribution model of the oligonucleotide is used to calculate the corresponding monoisotopic mass from the mass spectrum. For analysis of oligonucleotides (range 26-79 nucleotides), mass accuracy was 0.62 +/- 0.74 ppm (n = 280) and excellent accuracy and precision were sustained for 180 hr without use of a lock mass standard. PMID- 27684517 TI - Association between serum adropin level and burden of coronary artery disease in patients with non-ST elevation myocardial infarction. AB - OBJECTIVE: Previous studies revealed the relationship between stable coronary artery disease (CAD) and serum adropin level, but this relationship has not been investigated in patients with non-ST segment elevation myocardial infarction (NSTEMI). The present study is an analysis of the relationship between adropin and severity of CAD assessed based on SYNTAX score in patients with NSTEMI. METHODS: A total of 109 participants, 80 patients with NSTEMI and 29 healthy individuals, were prospectively enrolled in the study. Patients with NSTEMI were divided to 2 groups: high SYNTAX score (>=32) (35 patients) and low SYNTAX score (<32) (45 patients). Adropin level was measured from blood serum samples using enzyme-linked immunosorbent assay test. RESULTS: Patients with NSTEMI and high SYNTAX score had significantly lower serum adropin level (2357.30 pg/mL+/-821.58) compared to NSTEMI patients with low SYNTAX score (3077.00 pg/mL+/-912.86) and control group (3688.00+/-956.65). Adropin cut-off value for predicting high SYNTAX score on receiver-operating characteristic curve analysis was determined to be 2759 pg/mL, with a sensitivity of 63% and a specificity of 57%. Adropin was an independent predictor for high SYNTAX score (odds ratio=0.999; 95% confidence interval: 0.998-1.000; p=0.007). CONCLUSION: Adropin could be an alternative blood sample value for predicting severity of CAD. PMID- 27684519 TI - Comparison of application of 2013 ACC/AHA guideline and 2011 European Society of Cardiology guideline for the management of dyslipidemias for primary prevention in a Turkish cohort. AB - OBJECTIVE: Atherosclerotic cardiovascular disease is a major global cause of death. The common approach in primary prevention of cardiovascular disease is to identify patients at high risk for cardiovascular disease. This article analyzes and compares the application of 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline and the 2011 European Society of Cardiology (ESC) guideline for the management of dyslipidemias for primary prevention in Turkish population. METHODS: The study included 833 patients (482 women and 351 men). Risk scores were calculated according to both guidelines and indications for statin treatment were determined according to sex and age group. Variables are presented as mean+/-SD or median with interquartile range for continuous data and as proportions for categorical data. Variables were analyzed by unpaired t test, Mann-Whitney U test, chi-square or Fischer's exact test as appropriate. RESULTS: The ACC/AHA would suggest statin treatment in 415 patients out of 833 (49.5%), while ESC would recommend statin for 193 patients out of 833 (23.1%)(p<0.001). Statins would be recommended for 40.4% of women and 62.6% of men for primary prevention by the ACC/AHA, while this figure was 12% for women and 38.4% for men according to the ESC guideline (p<0.001 for both). CONCLUSION: When compared to the ESC guideline, the ACC/AHA guideline suggests augmented statin treatment for primary prevention in Turkish population. PMID- 27684520 TI - Flexible, Highly Sensitive, and Wearable Pressure and Strain Sensors with Graphene Porous Network Structure. AB - A mechanical sensor with graphene porous network (GPN) combined with polydimethylsiloxane (PDMS) is demonstrated by the first time. Using the nickel foam as template and chemically etching method, the GPN can be created in the PDMS-nickel foam coated with graphene, which can achieve both pressure and strain sensing properties. Because of the pores in the GPN, the composite as pressure and strain sensor exhibit wide pressure sensing range and highest sensitivity among the graphene foam-based sensors, respectively. In addition, it shows potential applications in monitoring or even recognize the walking states, finger bending degree, and wrist blood pressure. PMID- 27684518 TI - The impact of protein oxidation on sustained and white coat hypertension. AB - OBJECTIVE: The present study compared the unfavorable effects of protein oxidation and deoxyribonucleic acid damage on patients with white coat hypertension (WCH), sustained hypertension (HT), and normotensives. METHODS: Participants were allocated into 3 groups: 40 healthy controls, 36 patients with WCH, and 40 patients with sustained HT. Patients with risk factors for atherosclerosis, endocrine diseases, alcoholism, or masked hypertension were excluded. Plasma level of protein carbonyl (PCO), ischemia modified albumin (IMA), total thiol (T-SH), prooxidant-antioxidant balance (PAB), advanced protein oxidation products (AOPPs), and urinary level of 8-hydroxy-2'-deoxyguanosine (8 OHdG) were measured and relationship between these oxidative stress parameters and WCH and sustained HT was analyzed. RESULTS: Ambulatory 24-hour, daytime and night-time systolic and diastolic blood pressure readings of sustained HT group were significantly higher than those of WCH and control groups (p<0.001, all). AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher in HT group than WCH and control groups (p<0.001, all). Additionally, T-SH level was significantly lower in HT group than WCH and control groups (p<0.001). A similar statistically significant relationship was detected between WCH and control groups. CONCLUSION: Results indicate that increased level of AOPPs, PCO, IMA, 8 OHdG, PAB, and decreased level of T-SH are likely to be indicators of oxidative stress, which may play a key role both in WCH and sustained HT. PMID- 27684521 TI - Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice. AB - Despite global coverage of intradermal BCG vaccination, tuberculosis remains one of the most prevalent infectious diseases in the world. Preclinical data have encouraged pulmonary tuberculosis vaccines as a promising strategy to prevent pulmonary disease, which is responsible for transmission. In this work, we describe the methodology used to demonstrate in the mouse model the benefits of intranasal BCG vaccination when compared to subcutaneous. Our data revealed greater protective efficacy following intranasal BCG administration. In addition, our results indicate that pulmonary vaccination triggers a higher immune response in lungs, including Th1 and Th17 responses, as well as an increase of immunoglobulin A (IgA) concentration in respiratory airways. Our data show correlation between protective efficacy and the presence of IL17-producing cells in lungs post-Mycobacterium tuberculosis challenge, suggesting a role for this cytokine in the protective response conferred by pulmonary vaccination. Finally, we detail the global workflow we have developed to study respiratory vaccination in the mouse model, which could be extrapolated to other tuberculosis vaccines, apart from BCG, targeting the mucosal response or other pulmonary routes of administration such as the intratracheal or aerosol. PMID- 27684522 TI - Effectiveness of the Language Intervention Programme for Preschool Children. AB - OBJECTIVE: This paper investigates the effectiveness of the Language Intervention Programme for the treatment of 14 preschool-aged children with primary language impairment. PATIENTS AND METHODS: We used a waiting list control design, in which half the sample (7 children) received immediate intervention with the Language Intervention Programme, whereas the remaining children received treatment after a 4-week delay. The intervention consisted of 8 individual biweekly sessions. Outcome measures of language ability (receptive semantic and morphosyntactic, expressive semantic and morphosyntactic, and metalinguistic) were taken before and after intervention. RESULTS: After 4 weeks of intervention, the experimental group showed significant improvements in language (receptive, expressive and metalinguistic skills), but no differences were found for those in the waiting control group. After 4 weeks of intervention for the control group, significant progress in language was also observed. CONCLUSION: The Language Intervention Programme was found to be effective in treating language skills of children with language impairment, providing clinical evidence for speech and language therapists to employ this programme for the treatment of preschool children with language disorders. PMID- 27684523 TI - QSAR Model of Unbound Brain-to-Plasma Partition Coefficient, Kp,uu,brain: Incorporating P-glycoprotein Efflux as a Variable. AB - We report development and prospective validation of a QSAR model of the unbound brain-to-plasma partition coefficient, Kp,uu,brain, based on the in-house data set of ~1000 compounds. We discuss effects of experimental variability, explore the applicability of both regression and classification approaches, and evaluate a novel, model-within-a-model approach of including P-glycoprotein efflux prediction as an additional variable. When tested on an independent test set of 91 internal compounds, incorporation of P-glycoprotein efflux information significantly improves the model performance resulting in an R2 of 0.53, RMSE of 0.57, Spearman's Rho correlation coefficient of 0.73, and qualitative prediction accuracy of 0.8 (kappa = 0.6). In addition to improving the performance, one of the key advantages of this approach is the larger chemical space coverage provided indirectly through incorporation of the in vitro, higher throughput data set that is 4 times larger than the in vivo data set. PMID- 27684524 TI - Predictive Model Development for Aviation Black Carbon Mass Emissions from Alternative and Conventional Fuels at Ground and Cruise. AB - The first order approximation (FOA3) currently employed to estimate BC mass emissions underpredicts BC emissions due to inaccuracies in measuring low smoke numbers (SNs) produced by modern high bypass ratio engines. The recently developed Formation and Oxidation (FOX) method removes the need for and hence uncertainty associated with (SNs), instead relying upon engine conditions in order to predict BC mass. Using the true engine operating conditions from proprietary engine cycle data an improved FOX (ImFOX) predictive relation is developed. Still, the current methods are not optimized to estimate cruise emissions nor account for the use of alternative jet fuels with reduced aromatic content. Here improved correlations are developed to predict engine conditions and BC mass emissions at ground and cruise altitude. This new ImFOX is paired with a newly developed hydrogen relation to predict emissions from alternative fuels and fuel blends. The ImFOX is designed for rich-quench-lean style combustor technologies employed predominately in the current aviation fleet. PMID- 27684525 TI - Insect-machine Hybrid System: Remote Radio Control of a Freely Flying Beetle (Mercynorrhina torquata). AB - The rise of radio-enabled digital electronic devices has prompted the use of small wireless neuromuscular recorders and stimulators for studying in-flight insect behavior. This technology enables the development of an insect-machine hybrid system using a living insect platform described in this protocol. Moreover, this protocol presents the system configuration and free flight experimental procedures for evaluating the function of the flight muscles in an untethered insect. For demonstration, we targeted the third axillary sclerite (3Ax) muscle to control and achieve left or right turning of a flying beetle. A thin silver wire electrode was implanted on the 3Ax muscle on each side of the beetle. These were connected to the outputs of a wireless backpack (i.e., a neuromuscular electrical stimulator) mounted on the pronotum of the beetle. The muscle was stimulated in free flight by alternating the stimulation side (left or right) or varying the stimulation frequency. The beetle turned to the ipsilateral side when the muscle was stimulated and exhibited a graded response to an increasing frequency. The implantation process and volume calibration of the 3 dimensional motion capture camera system need to be carried out with care to avoid damaging the muscle and losing track of the marker, respectively. This method is highly beneficial to study insect flight, as it helps to reveal the functions of the flight muscle of interest in free flight. PMID- 27684526 TI - South-east Asian Zika virus strain linked to cluster of cases in Singapore, August 2016. AB - Zika virus (ZIKV) is an ongoing global public health emergency with 70 countries and territories reporting evidence of ZIKV transmission since 2015. On 27 August 2016, Singapore reported its first case of local ZIKV transmission and identified an ongoing cluster. Here, we report the genome sequences of ZIKV strains from two cases and find through phylogenetic analysis that these strains form an earlier branch distinct from the recent large outbreak in the Americas. PMID- 27684528 TI - Correction to "Synthesis of 2-Thiocarbohydrates and Their Binding to Concanavalin A". PMID- 27684527 TI - The effect of protonation of cytosine and adenine on their interactions with carbon nanotubes. AB - Placing electrical charges on nanomaterials is a means to extend their functional capabilities in nanoelectronics and sensoring applications. This paper explores the effect of charging nitrogen bases cytosine (Cyt) and adenine (Ade) via protonation on their noncovalent interaction with carbon nanotubes (CNT) using quantum chemical calculations performed at the M05-2X/6-31++G** level of theory alongside with a molecular graphics method. It is shown that the protonation of the bases causes threefold increase of the interaction energy in the CNT.Cyt.H+ and SNT.Ade.H+ complexes as compared to the CNT complexes formed with neutral bases. There is also some shortening of the base-CNT distance by ca 0.13A. The visualization of the electrostatic potential distribution with the molecular graphics reveals that the positive potential due to the protonated bases extends to a cylindrical domain of the nanotube segment adjacent to the base binding site. Furthermore, subtraction of the electrostatic potential maps of the protonated bases from the maps of their complexes with CNTs reveals an area of negative potential on the CNT surface, which reflects the location of the adsorbed base. The positive charge transfer of ca 0.3 e from the protonated bases to the CNT strengthens the interaction in the CNT.Cyt.H+ and SNT.Ade.H+ complexes. The analysis of the frontier orbitals shows that the LUMOs of the complexes mainly reside on the CNT, while the HOMOs spread over both components of each complex. The observed effects may facilitate the design of nanomaterials involving nitrogen bases and CNTs. PMID- 27684529 TI - Lower limb joint stiffness and muscle co-contraction adaptations to instability footwear during locomotion. AB - Unstable shoes (US) continually perturb gait which can train the lower limb musculature, but muscle co-contraction and potential joint stiffness strategies are not well understood. A shoe with a randomly perturbing midsole (IM) may enhance these adaptations. This study compares ankle and knee joint stiffness, and ankle muscle co-contraction during walking and running in US, IM and a control shoe in 18 healthy females. Ground reaction forces, three-dimensional kinematics and electromyography of the gastrocnemius medialis and tibialis anterior were recorded. Stiffness was calculated during loading and propulsion, derived from the sagittal joint angle-moment curves. Ankle co-contraction was analysed during pre-activation and stiffness phases. Ankle stiffness reduced and knee stiffness increased during loading in IM and US whilst walking (ankle, knee: p=0.008, 0.005) and running (p<0.001; p=0.002). During propulsion, the opposite joint stiffness re-organisation was found in IM whilst walking (both joints p<0.001). Ankle co-contraction increased in IM during pre-activation (walking: p=0.001; running: p<0.001), and loading whilst walking (p=0.003), not relating to ankle stiffness. Results identified relative levels of joint stiffness change in unstable shoes, providing new evidence of how stability is maintained at the joint level. PMID- 27684531 TI - Does physical exercise improve quality of life of advanced cancer patients? AB - PURPOSE OF REVIEW: We discuss the principal issues about physical activity in advanced cancer patients through the analyses of the last articles and our experience in this field. RECENT FINDINGS: The efficacy of exercise training intervention could improve quality of life (QOL), fatigue and well being in advanced cancer patients. Several published studies have included, nevertheless, patients with early stage of disease and more recently, populations of patients with local advanced tumors of the breast, rectum and lung, who are undergoing neoadjuvant therapy. Despite the insufficient sample of patients in these studies, physical exercise is considered to improve both cardiopulmonary function and physical muscle fitness. Cancer-related fatigue is a devastating symptom in advanced cancer patients that implies loss of mobility and independence. SUMMARY: Physical exercise could be a treatment to increase skeletal muscle endurance and improve well being. In palliative medicine, physical activity could be applied to medical assistance or to design prospective and controlled trials so as to evaluate possible usefulness. PMID- 27684530 TI - Fabrication of Inverted Colloidal Crystal Poly(ethylene glycol) Scaffold: A Three dimensional Cell Culture Platform for Liver Tissue Engineering. AB - The ability to maintain hepatocyte function in vitro, for the purpose of testing xenobiotics' cytotoxicity, studying virus infection and developing drugs targeted at the liver, requires a platform in which cells receive proper biochemical and mechanical cues. Recent liver tissue engineering systems have employed three dimensional (3D) scaffolds composed of synthetic or natural hydrogels, given their high water retention and their ability to provide the mechanical stimuli needed by the cells. There has been growing interest in the inverted colloidal crystal (ICC) scaffold, a recent development, which allows high spatial organization, homotypic and heterotypic cell interaction, as well as cell extracellular matrix (ECM) interaction. Herein, we describe a protocol to fabricate the ICC scaffold using poly (ethylene glycol) diacrylate (PEGDA) and the particle leaching method. Briefly, a lattice is made from microsphere particles, after which a pre-polymer solution is added, properly polymerized, and the particles are then removed, or leached, using an organic solvent (e.g., tetrahydrofuran). The dissolution of the lattice results in a highly porous scaffold with controlled pore sizes and interconnectivities that allow media to reach cells more easily. This unique structure allows high surface area for the cells to adhere to as well as easy communication between pores, and the ability to coat the PEGDA ICC scaffold with proteins also shows a marked effect on cell performance. We analyze the morphology of the scaffold as well as the hepatocarcinoma cell (Huh-7.5) behavior in terms of viability and function to explore the effect of ICC structure and ECM coatings. Overall, this paper provides a detailed protocol of an emerging scaffold that has wide applications in tissue engineering, especially liver tissue engineering. PMID- 27684532 TI - Adults with One or More Functional Disabilities - United States, 2011-2014. AB - Nearly 40 million persons in the United States have a disability, as defined by responses to six questions recommended by the U.S. Department of Health and Human Services as the national standard for identifying disabilities in population based health surveys (1). Although these questions have been used to estimate prevalence of functional disabilities overall, as well as types of functional disabilities (disability type), no study has yet investigated the characteristics of U.S. adults by number of disability types. Knowing the characteristics of persons living with multiple disability types is important for understanding the overall functional status of these persons. CDC analyzed data from the family component of the National Health Interview Survey (NHIS) for the years 2011-2014 to estimate the percentage of adults aged 18-64 years with one, two, three, or four or more disability types, by selected demographic and socioeconomic characteristics. Overall, 22.6 million (11.9%) working-age adults were found to have any disability, and in this population, most (12.8 million) persons had only one disability type. A generally consistent pattern between increasing indicators of low socioeconomic status and the number of disability types was observed. Understanding the demographic and socioeconomic characteristics of working-age adults with disabilities, including those with multiple disability types, might help to further the inclusion of persons with disabilities in public health programs and policies. PMID- 27684534 TI - An update clinical application of amniotic fluid-derived stem cells (AFSCs) in cancer cell therapy and tissue engineering. AB - Recent studies have elucidated that cell-based therapies are promising for cancer treatments. The human amniotic fluid stem (AFS) cells are advantageous cells for such therapeutic schemes that can be innately changed to express therapeutic proteins. HAFSCs display a natural tropism to cancer cells in vivo. They can be useful in cancer cells targeting. Moreover, they are easily available from surplus diagnostic samples during pregnancy and less ethical and legal concern are associated with the collection and application than other putative cells are subjected. This review will designate representatives of amniotic fluid and stem cell derived from amniotic fluid. For this propose, we collect state of human AFS cells data applicable in cancer therapy by dividing this approach into two main classes (nonengineered and engineered based approaches). Our study shows the advantage of AFS cells over other putative cells types in terms differentiation ability to a wide range of cells by potential and effective use in preclinical studies for a variety of diseases. This study has shown the elasticity of human AFS cells and their favorable potential as a multipotent cell source for regenerative stem cell therapy and capable of giving rise to multiple lineages including such as osteoblasts and adipocyte. PMID- 27684535 TI - Sensory Topography of Oral Structures. AB - Importance: Sensory function in the oral cavity and oropharynx is integral to effective deglutition and speech production. The main hurdle to evaluation of tactile consequences of upper aerodigestive tract diseases and treatments is access to a reliable clinical tool. We propose a rapid and reliable procedure to determine tactile thresholds using buckling monofilaments to advance care. Objective: To develop novel sensory testing monofilaments and map tactile thresholds of oral cavity and oropharyngeal structures. Design, Setting, and Participants: A prospective cross-sectional study of 37 healthy adults (12 men, 25 women), specifically without a medical history of head and neck surgery, radiation, or chemotherapy, was carried out in an academic tertiary medical center to capture normative data on tactile sensory function in oral structures. Interventions: Cheung-Bearelly monofilaments were constructed by securing nylon monofilament sutures (2-0 through 9-0) in the lumen of 5-French ureteral catheters, exposing 20 mm for tapping action. Main Outcomes and Measures: Buckling force consistency was evaluated for 3 lots of each suture size. Sensory thresholds of 4 oral cavity and 2 oropharyngeal subsites in healthy participants (n = 37) were determined by classical signal detection methodology (d-prime >=1). In 21 participants, test-retest reliability of sensory thresholds was evaluated. Separately in 16 participants, sensory thresholds determined by a modified staircase method were cross-validated with those obtained by classical signal detection. Results: Buckling forces of successive suture sizes were distinct (P < .001), consistent (Cronbach alpha, 0.99), and logarithmically related (r = 0.99, P < .001). Test-retest reliability of sensory threshold determination was high (Cronbach alpha, >0.7). The lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P < .001). Threshold determination by classical signal detection and modified staircase methods were highly correlated (r = 0.93, P < .001). Growth of perceptual intensity was logarithmically proportional to stimulus strength (P < .01). Conclusions and Relevance: Topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory and growth of perceptual intensity at all subsites is log-linear. Cheung-Bearelly monofilaments are accessible, disposable, and consistent esthesiometers. This novel clinical tool is deployable for quantitative sensory function assessment of oral cavity and oropharyngeal structures. PMID- 27684533 TI - RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial. AB - Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents. Design, Setting, and Participants: The neoadjuvant NeoALTTO trial randomized 455 women with HER2 positive early-stage breast cancer to trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The present substudy, which was planned in the NeoALTTO main protocol, evaluated the association of pretreatment gene expression levels defined using RNA sequencing with pCR and event-free survival (EFS). Main Outcomes and Measures: Gene expression-based biomarkers using RNA sequencing were examined for their association with response to anti-HER2 therapy and long-term outcome. Results: Sequencing data were available for 254 (56%) of the NeoALTTO participants (mean [SD] age of substudy participants, 48.8 [11.2] years). The expression of ERBB2/HER2 was the most significant predictor of pCR, followed by HER2-enriched subtype, ESR1, treatment arm, ER immunohistochemical analysis scores, Genomic Grade Index, immune, proliferation, and AKT/mTOR GSs. Adjusting for clinicopathological variables and treatment arms, ERBB2/HER2, HER2-enriched subtype, ESR1, and Genomic Grade Index remained significant. Immune GSs were associated with higher pCR only in the combination arm (odds ratio, 2.1; 95% CI, 1.2-4.0; interaction test P = .01), while the stroma GSs were significantly associated with higher pCR in the single arms and with lower pCR in the combination arm (odds ratio, 0.46; 95% CI, 0.25-0.84; P = .009). None of the evaluated variables was associated with EFS after correction for multiple testing, but this analysis was underpowered. Conclusions and Relevance: High levels of ERBB2/HER2 and low levels of ESR1 were associated with pCR in all treatment arms. In the combination arm, high expression of immune and stroma GSs were significantly associated with higher and lower pCR rates, respectively, and should be further explored as candidate predictive markers. Trial Registration: clinicaltrials.gov Identifier: NCT00553358. PMID- 27684536 TI - The role of colorism in explaining African American females' suspension risk. AB - African American female students' elevated suspension risk has received national attention. Despite a number of studies documenting racial/ethnic disparities in African American females' school suspension risk, few investigations have attempted to explain why these disparities occur. The purpose of this study was to examine the role of colorism in explaining suspension risk using a nationally representative sample of adolescent females. Controlling for individual- and school-level characteristics associated with school discipline such as student teacher relationships, prior discipline history, school size and type, the results indicate that colorism was a significant predictor of school suspension risk. African American female adolescents with darker complexions were almost twice as likely to receive an out-of-school suspension as their White female peers. This finding was not found for African American female students with lighter skin complexions. Implications for adopting a colorist framework for understanding school discipline outcomes and future research for advancing the field in this area are discussed. (PsycINFO Database Record PMID- 27684537 TI - Evaluating a computer flash-card sight-word recognition intervention with self determined response intervals in elementary students with intellectual disability. AB - A concurrent multiple-baseline across-tasks design was used to evaluate the effectiveness of a computer flash-card sight-word recognition intervention with elementary-school students with intellectual disability. This intervention allowed the participants to self-determine each response interval and resulted in both participants acquiring previously unknown words across all word sets. Discussion focuses on the need to evaluate and compare computer flash-card sight word recognition interventions with fixed and self-determined response intervals across students and dependent variables, including rates of inappropriate behavior and self-determination in students with intellectual disability. (PsycINFO Database Record PMID- 27684539 TI - Single measure and gated screening approaches for identifying students at-risk for academic problems: Implications for sensitivity and specificity. AB - Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state test scores with data collected during fall screening periods to identify at-risk students. In addition, the benefit of using previous state test scores in conjunction with data from a separate measure to identify at-risk students has not been explored. The diagnostic accuracy of 3 types of screening approaches were tested to predict proficiency on end-of-year high-stakes assessments: state test data obtained during the previous year, data from a different measure administered in the fall, and both measures combined (i.e., a gated model). Extant reading and math data (N = 2,996) from 10 schools in the Midwest were analyzed. When used alone, both measures yielded similar sensitivity and specificity values. The gated model yielded superior specificity values compared with using either measure alone, at the expense of sensitivity. Implications, limitations, and ideas for future research are discussed. (PsycINFO Database Record PMID- 27684538 TI - Observer and student ratings of the class environment: A preliminary investigation of convergence. AB - The present study examined the relationship between student and observer ratings of the class environment. More specifically, class responses on the Responsive Environmental Assessment for Classroom Teaching (REACT; Theodore J. Christ & Colleagues, 2015) were compared with observer ratings on the Classroom Strategies Assessment System-Observer Form (Reddy, Fabiano, & Dudek, 2013). This study included 38 teachers and 582 students from 5 high-poverty schools. Observational data were reported as discrepancy scores, which reflect the difference between the recommended frequency and observed frequency of specific instructional and behavioral management strategies for classroom teachers. Pearson correlations were used to evaluate the relationship between the 6 subscales included on the REACT and the 9 subscales included on the CSAS-O. Results provide preliminary evidence for the relationship between observer and student ratings of the class environment. More specifically, as discrepancy scores decreased, student ratings of the class environment tended to be more positive. The relationship between the REACT and the CSAS-O differed across subscales; however, in general, subscales that were conceptually similar tended to demonstrate stronger relationships than subscales that were conceptually distinct. Thus, the observed results also provide preliminary evidence that students are capable of discriminating between the quality of different components of the class environment. The potential use of both observer and student ratings of the class environment to provide teachers with a more robust and comprehensive reference for professional development purposes is discussed within the context of a tiered model of support. (PsycINFO Database Record PMID- 27684540 TI - Intravitreal anti-VEGF drug use in industrialized nations: why are newly introduced medications causing us to inject more and not less? PMID- 27684541 TI - Online attention modification for social anxiety disorder: replication of a randomized controlled trial. AB - Social anxiety disorder (SAD) models posit vigilance for external social threat cues and exacerbated self-focused attention as key in disorder development and maintenance. Evidence indicates a modified dot-probe protocol may reduce symptoms of SAD; however, the efficacy when compared to a standard protocol and long-term maintenance of treatment gains remains unclear. Furthermore, the efficacy of such protocols on SAD-related constructs remains relatively unknown. The current investigation clarified these associations using a randomized control trial replicating and extending previous research. Participants with SAD (n = 113; 71% women) were randomized to complete a standard (i.e. control) or modified (i.e. active) dot-probe protocol consisting of 15-min sessions twice weekly for four weeks. Self-reported symptoms were measured at baseline, post-treatment, and 4 month and 8-month follow-ups. Hierarchical linear modeling indicated significant self-reported reductions in symptoms of social anxiety, fear of negative evaluation, trait anxiety, and depression, but no such reductions in fear of positive evaluation. Symptom changes did not differ based on condition and were maintained at 8-month follow-up. Attentional biases during the dot-probe task were not related to symptom change. Overall, our results replicate support for the efficacy of both protocols in reducing symptoms of SAD and specific related constructs, and suggest a role of exposure, expectancy, or practice effects, rather than attention modification, in effecting such reductions. The current results also support distinct relationships between fears of negative and positive evaluation and social anxiety. Further research focused on identifying the mechanisms of change in attention modification protocols appears warranted. PMID- 27684542 TI - Protection of cumulus cells following dehydroepiandrosterone supplementation. AB - BACKGROUND: Growing studies have demonstrated that dehydroepiandrosterone (DHEA) may improve fertility outcomes in poor ovarian responders (PORs). The aim of this study was to compare clinical outcomes and cumulus cell (CC) expression before and after DHEA treatment in PORs undergoing in vitro fertilization (IVF) cycles. METHODS: Six patients with poor ovarian response were enrolled in the study according to Bologna criteria. DHEA was supplied at least 2 months before patients entered into the next IVF cycle. Expression of apoptosis-related genes in CCs was determined by quantitative real-time PCR. Mitochondrial dehydrogenase activity of CCs was assessed by cell counting kit-8 assay. RESULTS: Metaphase II oocytes, maturation rate, embryos at Day 3, and fertilization rate significantly increased following DHEA treatment. Expression of cytochrome c, caspase 9, and caspase 3 genes in CCs were significantly reduced after DHEA therapy. Additionally, increased mitochondrial activity of CCs was observed following DHEA supplementation. CONCLUSIONS: DHEA supplementation may protect CCs via improved mitochondrial activity and decreased apoptosis, leading to better clinical outcomes in PORs. PMID- 27684543 TI - The role of empowerment and quality of life in depression severity among unemployed people with affective disorders receiving mental healthcare. AB - PURPOSE: Sick leave and unemployment are highly prevalent among people with affective disorders. Their depression severity is disabling and inversely related to having employment. No evidence-based vocational rehabilitation exists for this target group. Knowledge is therefore needed to understand the psychosocial factors that affect depression severity in order to develop new rehabilitation interventions. This study examined relationships between depression severity and empowerment, working life aspirations, occupational engagement, and quality of life in unemployed people with affective disorders receiving mental healthcare. METHOD: In this cross-sectional study of 61 participants, instruments on psychosocial factors and questions on descriptive sociodemographic and clinical characteristics were administered. Descriptive, correlation, and regression statistics were applied. RESULTS: Correlation and regression analyses showed significant inverse relations between depression severity and empowerment and quality of life. The odds for more severe depression decreased with higher empowerment and quality of life. However, neither extent of engagement in daily life nor working life aspiration was related to depression severity. CONCLUSIONS: An empowerment approach and strategies, which support the quality of life, are needed in development of vocational rehabilitation interventions, and bridging of mental healthcare and vocational services. Implications for Rehabilitation Enhancing empowerment and quality life in the return to work process can decrease depression severity in unemployed people with affective disorder. There is a need to address work issues in addition to symptom reduction in primary and mental healthcare. Bridging the service and time gap between vocational rehabilitation and healthcare is recommended for mitigating long-term unemployment for people with affective disorders who want to work. PMID- 27684544 TI - A novel chemometric classification for FTIR spectra of mycotoxin-contaminated maize and peanuts at regulatory limits. AB - The rapid identification of mycotoxins such as deoxynivalenol and aflatoxin B1 in agricultural commodities is an ongoing concern for food importers and processors. While sophisticated chromatography-based methods are well established for regulatory testing by food safety authorities, few techniques exist to provide a rapid assessment for traders. This study advances the development of a mid infrared spectroscopic method, recording spectra with little sample preparation. Spectral data were classified using a bootstrap-aggregated (bagged) decision tree method, evaluating the protein and carbohydrate absorption regions of the spectrum. The method was able to classify 79% of 110 maize samples at the European Union regulatory limit for deoxynivalenol of 1750 ug kg-1 and, for the first time, 77% of 92 peanut samples at 8 ug kg-1 of aflatoxin B1. A subset model revealed a dependency on variety and type of fungal infection. The employed CRC and SBL maize varieties could be pooled in the model with a reduction of classification accuracy from 90% to 79%. Samples infected with Fusarium verticillioides were removed, leaving samples infected with F. graminearum and F. culmorum in the dataset improving classification accuracy from 73% to 79%. A 500 ug kg-1 classification threshold for deoxynivalenol in maize performed even better with 85% accuracy. This is assumed to be due to a larger number of samples around the threshold increasing representativity. Comparison with established principal component analysis classification, which consistently showed overlapping clusters, confirmed the superior performance of bagged decision tree classification. PMID- 27684545 TI - Assessment of food safety using a new real-time PCR assay for detection and quantification of virulence factors of enterococci in food samples. AB - AIMS: Development of Taqman MGB real-time PCR (q-PCR) assays for the quantitative detection of virulence factor genes in pure culture and food samples with regard to food safety assessment. METHODS AND RESULTS: New Taqman primers and probes were designed for the ace, esp and gelE genes based on the determinants of virulence profiles of enterococcal strains from GenBank. The high specificity and accuracy of the Taqman probe assay was confirmed. The limit of detection for the different virulence genes was 102 CFU ml-1 or CFU g-1 for pure culture and meat samples, and 103 CFU g-1 for cheese samples. CONCLUSION: This method provides the specific and rapid detection and quantification of ace, esp and gelE genes compared to conventional PCR assays, thus allowing the rapid and direct safety assessment of Enterococcus genus in food samples. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents efficient methods that can be used directly on food products for the rapid quantification and tracing of virulence genes, regarding food safety assessment. Moreover, this is the first study to quantify these virulence factors using a specific Taqman q-PCR assay in food samples. PMID- 27684546 TI - E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation. AB - RNF12/RLIM is a RING domain-containing E3 ubiquitin ligase whose function has only begun to be elucidated recently. Although RLIM was reported to play important roles in some biological processes such as imprinted X-chromosome inactivation and regulation of TGF-beta pathway etc., other functions of RLIM are largely unknown. Here, we identified RLIM as a novel E3 ubiquitin ligase for c Myc, one of the most frequently deregulated oncoproteins in human cancers. RLIM associates with c-Myc in vivo and in vitro independently of the E3 ligase activity of RLIM. Moreover, RLIM promotes the polyubiquitination of c-Myc protein independently of Ser62 and Thr58 phosphorylation of c-Myc. However, RLIM-mediated ubiquitination does not affect c-Myc stability. Instead, RLIM inhibits the transcriptional activity of c-Myc through which RLIM restrains cell proliferation. Our results suggest that RLIM may function as a tumor suppressor by controlling the activity of c-Myc oncoprotein. PMID- 27684547 TI - Parents' perceptions of counselling following prenatal diagnosis of congenital anomalies of the kidney and urinary tract: a qualitative study. AB - OBJECTIVES: To explore parents' experiences of counselling after prenatal diagnosis of congenital anomalies of the kidney and urinary tract. SUBJECTS AND METHODS: Parents of a child born between September 2012 and March 2015 with posterior urethral valves (PUV) or multicystic dysplastic kidney (MCDK) completed a semi-structured telephone interview, demographic survey, and the 21-item self report Depression, Anxiety and Stress Scales questionnaire. Qualitative data were analysed thematically using NVivo10 software. RESULTS: In all, 17 parents (PUV, eight; MCDK, nine) participated (response rate 40%), and most were offered counselling during pregnancy (14/17). Parents described feelings of shock, fear and uncertainty after diagnosis, and desired early information on all aspects of their child's condition. Most participants were satisfied with the information received; however, unmet information needs relating to treatment and prognosis were identified, particularly amongst fathers and parents in the PUV group. Some parents felt relieved after counselling (12/17); however, emotional distress often persisted long after diagnosis. Parents described a need for written and web-based information resources, specialised psychological services, and parent support groups. CONCLUSION: While parents valued counselling, many continued to report unmet informational and psychological needs. Early counselling addressing topics important to parents and provision of additional resources and support services may improve parents' adjustment to their baby's diagnosis. PMID- 27684548 TI - Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection. AB - AIMS AND OBJECTIVES: Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia reperfusion injury and the corollary renal dysfunction. METHODS: Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2MUg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. RESULTS: Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-alpha levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. CONCLUSION: The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications. PMID- 27684550 TI - Chronic alcoholics retain dyspeptic symptoms, pan-enteric dysmotility, and autonomic neuropathy before and after abstinence. AB - OBJECTIVE: To carry out a comprehensive study on gastrointestinal symptoms, motility and autonomic neuropathy in chronic alcoholics before and one year after abstinence. METHODS: Dyspeptic symptoms (questionnaires), fasting and postprandial gallbladder and gastric motility (ultrasonography), oro-cecal transit time (lactulose H2 -breath test), stool form score (indirect marker of colonic transit), and autonomic neuropathy (sweat spot test, R-R ratio) were assessed at baseline in 268 subjects (136 chronic alcoholics and 132 healthy controls). A subgroup of 39 patients was re-evaluated after 12 months of abstinence. RESULTS: Chronic alcoholics had increased dyspepsia, delayed gastric emptying and oro-cecal transit time but faster gallbladder emptying, with slightly accelerated colonic transit. Sympathetic, but not parasympathetic, autonomic dysfunction was found. Dyspeptic symptoms and functional alterations of gastric emptying and oro-cecal transit tests were still present after 12-month abstinence, whereas gallbladder motility, stool form score and sympathetic function improved. CONCLUSIONS: Chronic alcoholics exhibit combined and interdependent presence of dyspeptic symptoms, impaired motility at different levels of the gastrointestinal tract, with sympathetic dysfunction. Only a few of these abnormalities improve after one year of abstinence from alcohol. PMID- 27684549 TI - Structural Details of Ufd1 Binding to p97 and Their Functional Implications in ER Associated Degradation. AB - The hexameric ATPase p97 has been implicated in diverse cellular processes through interactions with many different adaptor proteins at its N-terminal domain. Among these, the Ufd1-Npl4 heterodimer is a major adaptor, and the p97 Ufd1-Npl4 complex plays an essential role in endoplasmic reticulum-associated degradation (ERAD), acting as a segregase that translocates the ubiquitinated client protein from the ER membrane into the cytosol for proteasomal degradation. We determined the crystal structure of the complex of the N-terminal domain of p97 and the SHP box of Ufd1 at a resolution of 1.55 A. The 11-residue-long SHP box of Ufd1 binds at the far-most side of the Nc lobe of the p97 N domain primarily through hydrophobic interactions, such that F225, F228, N233 and L235 of the SHP box contact hydrophobic residues on the surface of the p97 Nc lobe. Mutating these key interface residues abolished the interactions in two different binding experiments, isothermal titration calorimetry and co-immunoprecipitation. Furthermore, cycloheximide chase assays showed that these same mutations caused accumulation of tyrosinase-C89R, a well-known ERAD substrate, thus implying decreased rate of protein degradation due to their defects in ERAD function. Together, these results provide structural and biochemical insights into the interaction between p97 N domain and Ufd1 SHP box. PMID- 27684552 TI - Paul Broca's search for Basque skulls: The full story. AB - Paul Broca surmised that the short and broad-brachycephalic-skulls of the earliest European settlers had become longer and narrower-dolichocephalic-in modern populations due to the blending of different races. Swedish anatomist Anders Retzius had two brachycephalic skulls said to be from contemporary Basque individuals, a claim suited to test Broca's hypothesis. Broca worked with fellow anatomist and surgeon Pedro Gonzalez Velasco, the founding father of Spanish anthropology, to gather a large number of Basque skulls. In its time, this was the most fascinating collection owned by the Anthropological Society of Paris. This article explains how Broca and Velasco were able to gather such a sizeable array of specimens, which they had collected at a location known at first by the code name of "Z." Although Broca finally concluded that the origin of the Retzius skulls could not be determined, his research was to spark anthropologists' interest in the language and origins of the Basque people. PMID- 27684556 TI - English Pig Farmers' Knowledge and Behaviour towards African Swine Fever Suspicion and Reporting. AB - African swine fever (ASF) is a notifiable, virulent swine disease, and is a major threat to animal health and trade for many European Union (EU) countries. Early detection of the introduction of ASF virus is of paramount importance to be able to limit the potential extent of outbreaks. However, the timely and accurate reporting of ASF primary cases strongly depends on how familiar pig farmers are with the clinical signs, and their motivation to report the disease. Here, an online questionnaire survey was conducted between December 2014 and April 2015 to investigate English pig farmers' knowledge and behaviour towards ASF in terms of clinical suspicion and reporting. Multivariable logistic regression analysis was used to identify factors influencing the two variables of interest: 1) farmers who "would immediately suspect ASF" if they observed clinical signs of fever, lethargy, reduced eating and high mortality on their farm and 2) farmers who "would immediately report ASF" if they suspected ASF on their farm. The questionnaire was completed by 109 pig farmers. Results indicate that pig farmers having poor knowledge about ASF clinical signs and limited concern about ASF compared with other pig diseases are less likely to consider the possibility of an outbreak of ASF on their farm. In addition, pig farmers lacking awareness of outbreaks in other countries, having a perception of the negative impact on them resulting from false positive reporting and the perceived complexity of reporting procedures are less likely to report an ASF suspicion. These findings indicate important areas for educational campaigns targeted at English pig farmers to focus on in an attempt to increase the likelihood of a rapid response in the event of an ASF outbreak. PMID- 27684555 TI - Single Synonymous Mutations in KRAS Cause Transformed Phenotypes in NIH3T3 Cells. AB - Synonymous mutations in the KRAS gene are clustered at G12, G13, and G60 in human cancers. We constructed 9 stable NIH3T3 cell lines expressing KRAS, each with one of these synonymous mutations. Compared to the negative control cell line expressing the wild type human KRAS gene, all the synonymous mutant lines expressed more KRAS protein, grew more rapidly and to higher densities, and were more invasive in multiple assays. Three of the cell lines showed dramatic loss of contact inhibition, were more refractile under phase contrast, and their refractility was greatly reduced by treatment with trametinib. Codon usage at these glycines is highly conserved in KRAS compared to HRAS, indicating selective pressure. These transformed phenotypes suggest that synonymous mutations found in driver genes such as KRAS may play a role in human cancers. PMID- 27684557 TI - Early risk indicators for hand, foot and mouth disease clusters in China. PMID- 27684558 TI - Long-Term Correlation between Influenza Vaccination Coverage and Incidence of Influenza-Like Illness in 14 European Countries. AB - We aimed to examine the long-term correlation between influenza vaccination coverage and the incidence of influenza-like illness (ILI) in the total and elderly populations of European countries for which data was available on at least six consecutive influenza seasons. We graphically visualised vaccination coverage and ILI incidence trends and calculated Spearman rank correlation coefficients. Additionally, we fitted a negative binomial regression model to estimate the change in ILI incidence per percentage point change in vaccination coverage. We found significant negative correlations for the total population of the Netherlands (rho = -0.60, p-value = 0.003) and for the elderly populations of England (rho = -0.80, p-value < 0.001) and Germany (rho = -0.57, p-value = 0.04). However, results were not consistent, and for some countries we observed significant positive correlations. Only for the elderly in England was there a significant decline in incidence rate per percentage point increase in vaccination coverage (incidence rate ratio = 0.93; 95% confidence interval 0.88 0.99). Based on this ecological study it is not possible to provide evidence for a negative correlation between influenza vaccination coverage and ILI incidence. For future, aetiological studies to assess impact of influenza vaccinations on the population, there is a need for high quality data over long periods of time, on proportion of ILI caused by influenza virus infection, on severe outcome measures such as hospitalisation for influenza, and on other factors that potentially affect influenza transmission. PMID- 27684559 TI - The epithelial barrier and immunoglobulin A system in allergy. AB - Airway and intestinal epithelial layers represent first-line physical barriers, playing a key role in mucosal immunity. Barrier dysfunction, characterized by alterations such as disruption of cell-cell apical junctions and aberrant epithelial responses, probably constitutes early and key events for chronic immune responses to environmental antigens in the skin and in the gut. For instance, barrier dysfunction drives Th2 responses in atopic disorders or eosinophilic esophagitis. Such epithelial impairment is also a salient feature of allergic asthma and growing evidence indicates that barrier alterations probably play a driving role in this disease. IgA has been identified as the most abundant immunoglobulin in mucosa, where it acts as an active barrier through immune exclusion of inhaled or ingested antigens or pathogens. Historically, it has been thought to represent the serum factor underlying reaginic activity before IgE was discovered. Despite several studies about regulation and major functions of IgA at mucosal surfaces, its role in allergy remains largely unclear. This review aims at summarizing findings about epithelial functions and IgA biology that are relevant to allergy, and to integrate the emerging concepts and the recent developments in mucosal immunology, and how these could translate to clinical observations in allergy. PMID- 27684560 TI - Methods of milk expression for lactating women. AB - BACKGROUND: Breastfeeding is important, however not all infants can feed at the breast and methods of expressing milk need evaluation. OBJECTIVES: To assess acceptability, effectiveness, safety, effect on milk composition, contamination and costs of methods of milk expression. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 March 2016), handsearched relevant journals and conference proceedings, and contacted experts in the field to seek additional published or unpublished studies. We also examined reference lists of all relevant retrieved papers. SELECTION CRITERIA: Randomised and quasi randomised trials comparing methods at any time after birth. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: This updated review includes 41 trials involving 2293 participants, with 22 trials involving 1339 participants contributing data for analysis. Twenty-six of the trials referred to mothers of infants in neonatal units (n = 1547) and 14 to mothers of healthy infants at home (n = 730), with one trial containing mothers of both neonatal and healthy older infants (n = 16). Eleven trials compared one or more types of pump versus hand expression and 14 studies compared one type of pump versus another type of pump, with three of these studies comparing both hand expression and pump types. Twenty studies compared a specific protocol or adjunct behaviour including sequential versus simultaneous pumping protocols, pumping frequency, provision of an education and support intervention, relaxation, breast massage, combining hand expression with pumping and a breast cleansing protocol.Due to heterogeneity in participants, interventions, and outcomes measured or reported, we were unable to pool findings for most of the specified outcomes. It was not possible therefore to produce a 'Summary of findings' table in this update. Most of the included results were derived from single studies. Trials took place in 14 countries under a variety of circumstances and were published from 1982 to 2015. Sixteen of the 30 trials that evaluated pumps or products had support from the manufacturers. The risk of bias of the included studies was variable. Primary outcomesOnly one of the 17 studies examining maternal satisfaction/acceptability with the method or adjunct behaviour provided data suitable for analysis. In this study, self-efficacy was assessed by asking mothers if they agreed or disagreed with the following statement: 'I don't want anyone to see me (hand expressing/pumping)'. The study found that mothers who were using the electric pump were more likely to agree with the statement compared to mothers hand expressing, (mean difference (MD) 0.70, 95% confidence interval (CI) 0.15 to 1.25; P = 0.01, participants = 68). Mothers who were hand expressing reported that the instructions for expression were clearer compared to the electric pump, (MD -0.40, 95% CI -0.75 to -0.05; P = 0.02, participants = 68). Descriptive reporting of satisfaction in the other studies varied in the measures used, did not indicate a clear preference for one pump type, although there was satisfaction with some relaxation and support interventions.We found no clinically significant differences between methods related to contamination of the milk that compared any type of pump to hand expression (risk ratio (RR) 1.13, 95% CI 0.79 to 1.61; P = 0.51, participants = 28), manual pump compared to hand expression, (MD 0.20, 95% CI -0.18 to 0.58; P = 0.30, participants = 142) a large electric pump compared to hand expression (MD 0.10, 95% CI -0.29 to 0.49; P = 0.61, participants = 123), or a large electric pump compared to a manual pump (MD -0.10, 95% CI -0.46 to 0.26; P = 0.59, participants = 141).The level of maternal breast or nipple pain or damage was similar in comparisons of a large electric pump to hand expression (MD 0.02, 95% CI -0.67 to 0.71; P = 0.96, participants = 68). A study comparing a manual and large electric pump, reported sore nipples in 7% for both groups and engorgement in 4% using a manual pump versus 6% using an electric pump; and in one study no nipple damage was reported in the hand expression group, and one case of nipple damage in each of the manual pump and the large electric pump groups.One study examined adverse effects on infants, however as the infants did not all receive their mothers' expressed milk, we have not included the results. Secondary outcomesThe quantity of expressed milk obtained was increased, in some studies by a clinically significant amount, in interventions involving relaxation, music, warmth, massage, initiation of pumping, increased frequency of pumping and suitable breast shield size. Support programmes and simultaneous compared to sequential pumping did not show a difference in milk obtained. No pump consistently increased the milk volume obtained significantly.In relation to nutrient quality, hand expression or a large electric pump were found to provide higher protein than a manual pump, and hand expression provided higher sodium and lower potassium compared to a large electric pump or a manual pump. Fat content was higher with breast massage when pumping; no evidence of difference was found for energy content between methods.No consistent effect was found related to prolactin change or effect on oxytocin release with pump type or method. Economic aspects were not reported. AUTHORS' CONCLUSIONS: The most suitable method for milk expression may depend on the time since birth, purpose of expression and the individual mother and infant. Low-cost interventions including initiation of milk expression sooner after birth when not feeding at the breast, relaxation, massage, warming the breasts, hand expression and lower cost pumps may be as effective, or more effective, than large electric pumps for some outcomes. Variation in nutrient content across methods may be relevant to some infants. Small sample sizes, large standard deviations, and the diversity of the interventions argue caution in applying these results beyond the specific method tested in the specific settings. Independently funded research is needed for more trials on hand expression, relaxation and other techniques that do not have a commercial potential. PMID- 27684554 TI - Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model. AB - While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model. Using a stochastic model of fiber repair, it is assumed that mechanically damaged fibers are repaired longer, whereas proteolytically damaged fibers are repaired shorter, relative to their pre-damage length. To study adaptation of tendon properties to applied load, our model musculotendon unit is a simplified three-component Hill-type model of the human Achilles-soleus unit. Our model results demonstrate that the geometric equilibrium state of the Achilles tendon can coincide with minimization of the total metabolic cost of muscle activation. The proposed tendon model independently predicts rates of collagen fiber turnover that are in general agreement with in vivo experimental measurements. While the computational model here only represents a first step in a new approach to understanding the complex process of tendon remodeling in vivo, given these findings, it appears likely that the proposed framework may itself provide a useful theoretical foundation for developing valuable qualitative and quantitative insights into tendon physiology and pathology. PMID- 27684561 TI - Effect of Polyaryl Hydrocarbons on Cytotoxicity in Monocytic Cells: Potential Role of Cytochromes P450 and Oxidative Stress Pathways. AB - BACKGROUND: Benzo(a)pyrene (BaP), naphthalene (NPh), phenanthrene (Phe), benzo(a)antharacene (BeA), and benzo(b)fluoranthene (BeF) are known carcinogenic polyaryl hydrocarbons (PAHs) present in cigarette smoke. This study was designed to examine the relative effect of these constituents on the cytotoxicity of monocytic cells and the possible mechanism of PAH-mediated cytotoxicity. METHODS: We examined the acute (6-24 hours) and chronic (7 days) effects of these PAHs on the expression of cytochromes P450 (CYPs), oxidative stress, and cytotoxicity. The treated cells were examined for mRNA and protein levels of CYPs (1A1 and 3A4) and antioxidants enzymes (AOEs) superoxide dismutase-1 (SOD1) and catalase. Further, we assessed the levels of reactive oxygen species (ROS), caspase-3 cleavage activity, and cell viability. We performed these experiments in U937 and/or primary monocytic cells. RESULTS: Of the five PAHs tested, after chronic treatment only BaP (100 nM) showed a significant increase in the expression of CYP1A1, AOEs (SOD1 and catalase), ROS generation, caspase-3 cleavage activity, and cytotoxicity. However, acute treatment with BaP showed only an increase in the mRNA expression of CYP1A1. CONCLUSIONS: These results suggest that of the five PAHs tested, BaP is the major contributor to the toxic effect of PAHs in monocytic cells, which is likely to occur through CYP and oxidative stress pathways. PMID- 27684562 TI - Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication. AB - Prions are the infectious agents causing transmissible spongiform encephalopathies (TSE), progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD) of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to prion disease. This phenomenon raises the question whether such antibodies induce infectious prions de novo. Here we exposed cerebellar organotypic cultured slices (COCS) to the neurotoxic antibody, POM1. We then inoculated COCS homogenates into tga20 mice, which overexpress PrPC and are commonly utilized as sensitive indicators of prion infectivity. None of the mice inoculated with COCS-derived lysates developed any signs of disease, and all mice survived for at least 200 days post-inoculation. In contrast, all mice inoculated with bona fide prions succumbed to TSE after 55-95 days. Post-mortem analyses did not reveal any signs of prion pathology in mice inoculated with POM1-COCS lysates. Also, lysates from POM1-exposed COCS were unable to convert PrP by quaking. Hence, anti-GD antibodies do not catalyze the generation of prion infectivity. These data indicate that prion replication can be separated from prion toxicity, and suggest that anti-GD antibodies exert toxicity by acting downstream of prion replication. PMID- 27684563 TI - Formulation and in vitro and in vivo evaluation of a new osteoprotegerin-chitosan gel for bone tissue regeneration. AB - The osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. The study aimed to determine the physicochemical properties and biocompatibility of a newly formulated OPG chitosan gel. The OPG-chitosan gel was formulated using human OPG protein and water-soluble chitosan. The physicochemical properties were determined using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Gel morphology was determined using scanning electron microscopy (SEM) and then it was subjected to a protein release assay and biodegradability test. An in vitro cytotoxicity test on normal human periodontal ligament (NHPL) fibroblasts and normal human (NH) osteoblasts was carried out using the AlamarBlue assay. In vivo evaluation in a rabbit model involved creating critical-sized defects in calvarial bone, filling with the OPG chitosan gel and sacrificing at 12 weeks. In vitro results demonstrated that the 25 kDa OPG-chitosan gel had the highest rate of protein release and achieved 90% degradation in 28 days. At 12 weeks, the defects filled with 25 kDa OPG-chitosan gel showed significant (p < 0.05) new bone formation and the highest expression of osteocalcin and osteopontin compared to controls. Thus, the 25 kDa OPG chitosan gel could be a promising new biomaterial for tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 398-407, 2017. PMID- 27684564 TI - Gang masculinity and high-risk sexual behaviours. AB - High-risk sexual behaviours include practices such as relationship violence and substance use, which often cluster together among young people in high-risk settings. Youth gang members often show high rates of such behaviours, substance use and relationship violence. This paper draws on data from in-depth interviews with male and female gang members from six different gangs to explore the role of powerful socialising peer groups that set gender, sexual and relationship roles and expectations for their male and female members. High-risk sexual behaviours among gang members included sex with multiple partners and group sex. Gang norms included the belief that male members were sexually insatiable with multiple sexual partners and that female gang members should be sexually available to male members. Alcohol and drugs were seen to have a large influence on sexual desire and the inability to use condoms. Much sexual behaviour with gangs, such as group sex, was viewed with ambivalence and seen as somewhat coercive. Finally, gendered sexual expectations (boys as sexually insatiable and girls as sexually available) made forming long-term romantic relationships problematic for gang members. The influence of gang norms such as these must be addressed in future programmes and interventions with gang members. PMID- 27684565 TI - Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum. AB - Mutations in GLE1 cause two recessive subtypes of arthrogryposis multiplex congenita (AMC), a condition characterized by joint contractures at birth, and all previously reported patients died in the perinatal period. GLE1 related AMC has been almost exclusively reported in the Finnish population and is caused by a relatively common pathogenic splicing mutation in that population. Here, we report two non-Finnish brothers with novel compound heterozygous splicing mutations in GLE1, one of whom has survived to 12 years of age. We also demonstrate low levels of residual wild type transcript in fibroblasts from the surviving brother, suggesting that this residual wild-type transcript may contribute to the relatively longer-term survival in this family. We provide a detailed clinical report on the surviving patient, providing the first insight into the natural history of this rare neuromuscular disease. We also suggest that lethal congenital contracture syndrome 1 (LCCS1) and lethal arthrogryposis with anterior horn disease (LAAHD), the two AMC subtypes related to GLE1, do not have sufficient clinical or molecular differentiation to be considered allelic disorders. Rather, GLE1 mutations cause a variable spectrum of AMC severity including a non-lethal variant described herein. PMID- 27684568 TI - Scanning electron microscopy of the adhesion of Treponema pallidum subspecies pallidum (Nichol strain) to human brain microvascular endothelial cells in vitro. PMID- 27684566 TI - Adiponectin and pro-inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus. AB - AIMS/INTRODUCTION: Adipose tissue-derived hormones are associated with metabolic disorders including type 2 diabetes mellitus. The present study investigated the levels of adiponectin and pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and IL-10 in Vietnamese patients with type 2 diabetes mellitus, and their correlations with clinical parameters of overweight and type 2 diabetes mellitus. MATERIALS AND METHODS: Based on body mass index, 73 patients with type 2 diabetes mellitus were categorized either as overweight or non-overweight. As healthy controls, 57 overweight and non-overweight individuals without type 2 diabetes mellitus were included. The adiponectin, TNF-alpha, IL-1beta and IL-10 levels were measured in the sera samples in all study participants by enzyme-linked immunosorbent assay and were correlated with clinical parameters. RESULTS: The adiponectin levels were lower in patients with type 2 diabetes mellitus (2.5 +/- 1.5 MUg/mL) compared with controls (16 +/- 18.6 MUg/mL; P < 0.0001), and were decreased in overweight individuals compared with those who were not overweight. The TNF-alpha and IL-1beta levels were increased, whereas the IL-10 levels were decreased in patients with type 2 diabetes mellitus and in overweight controls compared with non-overweight controls (P < 0.0001). The adiponectin levels were correlated with the TNF-alpha, IL-1beta, IL-10 levels, and the clinical parameters of overweight and type 2 diabetes mellitus. The quantitative insulin sensitivity check index and homeostasis model assessment insulin resistance indexes were correlated with the relative ratios of adiponectin/TNF-alpha, adiponectin/IL-1beta, adiponectin/IL-10, TNF-alpha/IL-10 and IL-1beta/IL-10. CONCLUSIONS: Adiponectin and pro-inflammatory cytokines are associated with type 2 diabetes mellitus, and might serve as a prognostic marker and a therapeutic intervention for overweight related type 2 diabetes mellitus. PMID- 27684567 TI - Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants. METHODS: A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated. RESULTS: Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80% 30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR. CONCLUSION: NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination. PMID- 27684570 TI - Hyperbaric oxygen therapy promotes wound repair in ischemic and hyperglycemic conditions, increasing tissue perfusion and collagen deposition. AB - The treatment of chronic wounds remains inconsistent and empirical. Hyperbaric oxygen therapy (HBOT) is a promising method to improve wound repair but there is still a lack of understanding of its mechanisms of action and its indications are not yet clearly defined. We studied the effects of HBOT in four different wound conditions by inflicting bilateral wounds on the dorsal aspect of the feet of nonischemic or ischemic limbs in normoglycemic or hyperglycemic rats. To create an ischemic condition, arterial resection was performed unilaterally. Forty-four animals received HBOT five times a week until complete wound closure. Wound repair was compared with 44 rats receiving standard dressing only. HBOT increased blood flow and accelerated wound closure in ischemic and hyperglycemic wounds, most significantly when the two conditions were combined. Wound contraction and reepithelialization were similarly stimulated by HBOT. The acceleration of wound contraction was not associated with increased myofibroblasts expression, nor fibroblast recruitment or higher cell count in the granulation tissue. Of note, we observed a significant increase in collagen deposition in early time points in ischemic wounds receiving HBOT. This data emphasizes that an early application of HBOT might be crucial to its efficacy. We concluded that wounds where ischemia and hyperglycemia are combined, as it is often the case in diabetic patients, have the best chance to benefit from HBOT. PMID- 27684569 TI - Three Dimensional Human Neuro-Spheroid Model of Alzheimer's Disease Based on Differentiated Induced Pluripotent Stem Cells. AB - The testing of candidate drugs to slow progression of Alzheimer's disease (AD) requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuro-spheroid from induced pluripotent stem cells (iPSC) derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture. We characterized neuronal markers of our 3D neurons by immunocytochemical staining to validate the differentiation status. To block the generation of pathologic amyloid beta peptides (Abeta), the 3D-differentiated AD neurons were treated with inhibitors targeting beta-secretase (BACE1) and gamma secretases. As predicted, both BACE1 and gamma-secretase inhibitors dramatically decreased Abeta generation in iPSC-derived neural cells derived from all five AD patients, under standard two-dimensional (2D) differentiation conditions. However, BACE1 and gamma-secretase inhibitors showed less potency in decreasing Abeta levels in neural cells differentiated under 3D culture conditions. Interestingly, in a single subject AD1, we found that BACE1 inhibitor treatment was not able to significantly reduce Abeta42 levels. To investigate underlying molecular mechanisms, we performed proteomic analysis of 3D AD human neuronal cultures including AD1. Proteomic analysis revealed specific reduction of several proteins that might contribute to a poor inhibition of BACE1 in subject AD1. To our knowledge, this is the first iPSC-differentiated 3D neuro-spheroid model derived from AD patients' blood. Our results demonstrate that our 3D human neuro spheroid model can be a physiologically relevant and valid model for testing efficacy of AD drug. PMID- 27684571 TI - Effect of Dose on Intra-Articular Amikacin Sulfate Concentrations Following Intravenous Regional Limb Perfusion in Horses. AB - OBJECTIVE: To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. STUDY DESIGN: Randomized crossover experiment. ANIMALS: Six adult horses. METHODS: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and >=14 days washout period). Amikacin concentrations were quantified in synovial fluid collected from the middle carpal and metacarpophalangeal joints at 25 minutes, and 24, 36, and 48 hours after IVRLP. Minimum inhibitory concentrations (MIC) were determined from equine bacterial isolates and ability to reach target amikacin concentrations were compared. RESULTS: Overall, middle carpal joint amikacin concentrations were higher following IVRLP with 3 g amikacin compared to 2 g (P=.031), with significant differences at 25 minutes (P=.002) and 24 hours (P=.021). No differences were observed between doses in the metacarpophalangeal joint (P=.267). Target amikacin concentrations for Staphylococcus aureus and coagulase-negative staphylococci were achieved in middle carpal and metacarpophalangeal joints at 25 minutes with both dosages and for Escherichia coli and Actinobacillus spp. in the middle carpal joint at 25 minutes with 3 g. Target concentrations were not achieved for Enterococcus spp, Pseudomonas spp, or Streptococcus equi ssp. zooepidemicus. CONCLUSION: A 3 g amikacin dose is not justified in the majority of distal limb injuries, but should be reserved for isolates with an MIC higher than that achievable with a 2 g dose. Daily IVRLP may be necessary based on our results. PMID- 27684572 TI - Development and application of neuropsychology in Hong Kong: implications of its value and future advancement. AB - OBJECTIVE: To review the development, application, and value of neuropsychology, and the standard education and training pathway for neuropsychologists or clinical neuropsychologists in Hong Kong. METHOD: The information provided here was gathered via a literature review of the status of neuropsychology and the validity of commonly adopted neuropsychological tests in Hong Kong. Additional details were acquired via the internet about local tertiary education curricula and the related requirements, the availability of professional associations for licensure or board certification, and relevant statistics/surveys conducted by the government. Some information about the clinical practice of neuropsychology was collected through personal communication with local clinical psychologists. RESULTS: The development of neuropsychology in Hong Kong over the past 20 years is rapid and productive, given the increasing application of advanced neuroimaging techniques, neuropsychological tests, and opportunities for exchanging up-to-date neuropsychological knowledge and professional training through international conferences, workshops, and seminars. Given that neuropsychology services are often provided by clinical psychologists who are master's degree graduates in clinical psychology, the relatively limited training in neuropsychological knowledge and skills and the lack of division for membership or mandatory registration as a neuropsychologist/clinical neuropsychologist may have an impact on the quality of clinical neuropsychological services and the development of this specialty. CONCLUSIONS: These findings signify a need for further improvement or refinement of educational and training pathways for neuropsychologist or clinical neuropsychologist along with the recognition of its value in clinical practice through registration of different disciplines of psychology in Hong Kong. PMID- 27684573 TI - Optimizing Trial Designs for Targeted Therapies. AB - An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment is tested in an overall population and/or in a pre-specified subpopulation. Based on a decision theoretic framework we derive optimized trial designs by maximizing utility functions. Features to be optimized include the sample size and the population in which the trial is performed (the full population or the targeted subgroup only) as well as the underlying multiple test procedure. The approach accounts for prior knowledge of the efficacy of the drug in the considered populations using a two dimensional prior distribution. The considered utility functions account for the costs of the clinical trial as well as the expected benefit when demonstrating efficacy in the different subpopulations. We model utility functions from a sponsor's as well as from a public health perspective, reflecting actual civil interests. Examples of optimized trial designs obtained by numerical optimization are presented for both perspectives. PMID- 27684574 TI - Prevalence of bruxism in undergraduate students. AB - OBJECTIVE: The aim of this study was to determine the prevalence of bruxism in students at the Federal University of the Jequitinhonha and Mucuri Valleys in Brazil. The secondary objectives were to identify the factors associated with bruxism; prevalence of dental wear; and to distinguish the signs and symptoms of temporomandibular dysfunction when present, and verify its relationship with bruxism. METHODS: Two hundred fifty-three students (106 males, 147 females) were clinically examined and answered a questionnaire. Trained researchers performed the dental wear evaluation. The incisal edge and occlusal surface were classified as follows: no wear, wear into enamel, wear into dentin, and extensive wear into dentin. Demographic data and factors related to bruxism were obtained by a questionnaire. The participants who presented dental wear and habit of clenching/grinding teeth were classified as bruxers. The data were analyzed by the SPSS program (p < 0.05). RESULTS: The results showed that 31.6% of the students had bruxism. Of the 7084 teeth evaluated, 376 (5.3%) had some type of facet wear. The teeth that had the highest prevalence of wear facets were the canines. Stress, muscle pain, temporomandibular joint (TMJ) pain, and TMJ noise were significantly associated with bruxism (p < 0.001). CONCLUSION: The prevalence of bruxism was 31.6% in this population. The factors most associated with bruxism were stress, muscle pain, TMJ pain, and TMJ noise. PMID- 27684575 TI - Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS 4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab. AB - The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS 4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL. PMID- 27684576 TI - Effect of liming on nickel bioavailability and toxicity to oat and soybean grown in field soils containing aged emissions from a nickel refinery. AB - Remediation of soils elevated in trace metals so that the soils may provide ecosystems services is typically achieved through pH adjustment or addition of sorbents. The present study aimed to generate higher-tier in situ toxicity data for elevated nickel (Ni) in soils with and without lime addition and to explore the effect of liming on soil chemistry and bioavailability of Ni to plants. A multiyear study of agronomic yield of field-grown oat and soybean occurred in 3 adjacent fields that had received air emissions from a Ni refinery for 66 yr. The soil Ni concentration in the plots ranged between 1300 mg/kg and 4900 mg/kg, and each field was amended with either 50 Mg/ha, 10 Mg/ha, or 0 Mg/ha (or tonnes/ha) of crushed dolomitic limestone. As expected, liming raised the pH of the soils and subsequently reduced the plant availability of Ni. Toxicity thresholds (effective concentrations causing 50% reduction in growth) for limed soils supported the hypothesis that liming reduces toxicity. Relationships were found between relative yield and soil cation exchange capacity and between relative yield and soil pH, corroborating findings of the European Union Risk Assessments and the Metals in Asia studies, respectively. Higher tier ecotoxicity data such as these are a valuable contribution to risk assessment for Ni in soils. Environ Toxicol Chem 2017;36:1110-1119. (c) 2016 SETAC. PMID- 27684577 TI - Micro-Magellan: open-source, sample-adaptive, acquisition software for optical microscopy. PMID- 27684578 TI - The NIH Protein Capture Reagents Program (PCRP): a standardized protein affinity reagent toolbox. PMID- 27684580 TI - Genomics in 3D and 4D. PMID- 27684579 TI - DoCM: a database of curated mutations in cancer. PMID- 27684581 TI - Young blood for old hands? A recent anti-ageing trial prompts ethical questions. PMID- 27684582 TI - Learning to listen in primary care: some educational challenges. AB - Effective clinician listening and communicating directly affects patients' health, satisfaction with healthcare, and complaints. This influences healthcare policy and clinician training/assessment. Listening skills and consultation frameworks underpin training but are often poorly used in everyday clinical work. Primary care doctors provide continuity of care using listening skills to develop long term relationships. Additionally, they listen to patients and colleagues in other ways such as surveys, participation groups, and significant event reviews. All these factors challenge educators to offer systematic training which ensures that future primary care clinicians/leaders develop conscious competence in listening at different levels and in differing contexts. PMID- 27684583 TI - Emergency contraception: a survey of 1773 women. AB - OBJECTIVES: The aim of the study was to retrieve data on the characteristics and profile of women attending an emergency service (ES) to receive a prescription (mandatory until May 2015) for emergency contraception (EC). METHODS: In a retrospective study the following data were collected for all women requesting EC between January 2014 and June 2015: demographic characteristics, time between unprotected sexual intercourse (USI) and arrival at the ES, time between the last menstrual period and the USI, and type of EC prescribed. In a prospective study starting January 2015, a questionnaire was administered requesting the following information: reasons for requiring EC, previous EC use, source of knowledge about EC, prior contraception and age at first intercourse. RESULTS: During the whole study period, 1773 women requested EC: their mean age was 26.0 years; 78.5% were Italian; 91.5% were unmarried; 55.2% were still studying and 51.9% had high school education; 61.2% reached the ES within 12 h of the USI; and 42.4% had a USI during days 9-16 of their menstrual cycle. Levonorgestrel was prescribed in 81.4% of women and ulipristal acetate in 17.7%. In the prospective part of the study (382 women), the majority (57.9%) requested EC for condom rupture; 49.5% reported previous use of EC; and 41.6% received information on the subject through friends. The vast majority (83.8%) reported prior use of contraception; in 25.4% the reason for not using it was the absence of a relationship. CONCLUSION: An exact profile of women requesting EC can help women in their choice of permanent contraception, and help clinicians in counselling women on appropriate contraception. PMID- 27684584 TI - Preparation of Extracellular Matrix Protein Fibers for Brillouin Spectroscopy. AB - Brillouin spectroscopy is an emerging technique in the biomedical field. It probes the mechanical properties of a sample through the interaction of visible light with thermally induced acoustic waves or phonons propagating at a speed of a few km/sec. Information on the elasticity and structure of the material is obtained in a nondestructive contactless manner, hence opening the way to in vivo applications and potential diagnosis of pathology. This work describes the application of Brillouin spectroscopy to the study of biomechanics in elastin and trypsin-digested type I collagen fibers of the extracellular matrix. Fibrous proteins of the extracellular matrix are the building blocks of biological tissues and investigating their mechanical and physical behavior is key to establishing structure-function relationships in normal tissues and the changes which occur in disease. The procedures of sample preparation followed by measurement of Brillouin spectra using a reflective substrate are presented together with details of the optical system and methods of spectral data analysis. PMID- 27684586 TI - Infrared Spectroscopy of NaCl(CH3OH)n Complexes in Helium Nanodroplets. AB - Infrared (IR) spectra of complexes between NaCl and methanol have been recorded for the first time. These complexes were formed in liquid helium nanodroplets by consecutive pick-up of NaCl and CH3OH molecules. For the smallest NaCl(CH3OH)n, complexes where n = 1-3, the IR data suggest that the lowest-energy isomer is the primary product in each case. The predominant contribution to the binding comes from ionic hydrogen bonds between the OH in each methanol molecule and the chloride ion in the NaCl, as established by the large red shift of the OH stretching bands compared with the isolated CH3OH molecule. For n >= 4, there is a dramatic shift from discrete vibrational bands to very broad absorption envelopes, suggesting a profound change in the structural landscape and, in particular, access to multiple low-energy isomers. PMID- 27684585 TI - Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS). AB - Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed. PMID- 27684587 TI - Understanding the Inter-relationship Between Periodontitis and Diabetes: Current Evidence and Clinical Implications. AB - Periodontal disease can impact systemic health through both direct and indirect mechanisms. Of the numerous periodontal-systemic inter-relationships studied, diabetes mellitus has been perhaps the most extensively evaluated. This article discusses the evidence and implications of periodontitis related to type 2 diabetes, focusing on the epidemiology of periodontal disease and diabetes as well as the periodontitis- diabetes continuum. PMID- 27684588 TI - The Evolution and Revolution in Prosthodontics Continues. AB - The rate of innovations in prosthodontics has been picking up considerable momentum and products have emerged, demonstrating superb strength and high esthetics. Trends indicate a preference for metal-free restorations, as the offerings of zirconia products have become more nuanced. Also, innovative scanning systems provide dental teams a greater flexibility and enhanced productivity. PMID- 27684589 TI - Measuring Spray Droplet Size from Agricultural Nozzles Using Laser Diffraction. AB - When making an application of any crop protection material such as an herbicide or pesticide, the applicator uses a variety of skills and information to make an application so that the material reaches the target site (i.e., plant). Information critical in this process is the droplet size that a particular spray nozzle, spray pressure, and spray solution combination generates, as droplet size greatly influences product efficacy and how the spray moves through the environment. Researchers and product manufacturers commonly use laser diffraction equipment to measure the spray droplet size in laboratory wind tunnels. The work presented here describes methods used in making spray droplet size measurements with laser diffraction equipment for both ground and aerial application scenarios that can be used to ensure inter- and intra-laboratory precision while minimizing sampling bias associated with laser diffraction systems. Maintaining critical measurement distances and concurrent airflow throughout the testing process is key to this precision. Real time data quality analysis is also critical to preventing excess variation in the data or extraneous inclusion of erroneous data. Some limitations of this method include atypical spray nozzles, spray solutions or application conditions that result in spray streams that do not fully atomize within the measurement distances discussed. Successful adaption of this method can provide a highly efficient method for evaluation of the performance of agrochemical spray application nozzles under a variety of operational settings. Also discussed are potential experimental design considerations that can be included to enhance functionality of the data collected. PMID- 27684590 TI - Temperature-Switch Cytometry-Releasing Antibody on Demand from Inkjet-Printed Gelatin for On-Chip Immunostaining. AB - Complete integration of all sample preparation steps in a microfluidic device greatly benefits point-of-care diagnostics. In the most simplistic approach, reagents are integrated in a microfluidic chip and dissolved upon filling with a sample fluid by capillary force. This will generally result in at least partial reagent wash-off during sample inflow. However, many applications, such as immunostaining-based cytometry, strongly rely on a homogeneous reagent distribution across the chip. The concept of initially preventing release (during inflow), followed by a triggered instantaneous and complete release on demand (after filling is completed) represents an elegant and simple solution to this problem. Here, we realize this controlled release by embedding antibodies in a gelatin layer integrated in a microfluidic chamber. The gelatin/antibody layer is deposited by inkjet printing. Maturation of this layer during the course of several weeks, due to the ongoing physical cross-linking of gelatin, slows down the antibody release, thereby reducing antibody wash-off during inflow, and consequently helping to meet the requirement for a homogeneous antibody distribution in the filled chamber. After inflow, complete antibody release is obtained by heating the gelatin layer above its sol-gel transition temperature, which causes the rapid dissolution of the entire gelatin/antibody layer at moderate temperatures. We demonstrate uniform and complete on-chip immunostaining of CD4 positive (CD4+) T-lymphocytes in whole blood samples, which is critical for accurate cell counts. The sample preparation is realized entirely on-chip, by applying temperature-switched antibody release from matured gelatin/antibody layers. PMID- 27684591 TI - Taste Preference Assay for Adult Drosophila. AB - Olfactory and gustatory perception of the environment is vital for animal survival. The most obvious application of these chemosenses is to be able to distinguish good food sources from potentially dangerous food sources. Gustation requires physical contact with a chemical compound which is able to signal through taste receptors that are expressed on the surface of neurons. In insects, these gustatory neurons can be located across the animal's body allowing taste to play an important role in many different behaviors. Insects typically prefer compounds containing sugars, while compounds that are considered bitter tasting are avoided. Given the basic biological importance of taste, there is intense interest in understanding the molecular mechanisms underlying this sensory modality. We describe an adult Drosophila taste assay which reflects the preference of the animals for a given tastant compound. This assay may be applied to animals of any genetic background to examine the taste preference for a desired soluble compound. PMID- 27684592 TI - Preparation of gold- and chlorine-impregnated bead-type activated carbon for a mercury sorbent trap. AB - This study aimed to develop a mercury (Hg) adsorption trap, which can be used to measure the concentration of elemental Hg in emissions from a Hg discharge facility, and evaluate its adsorption efficiency. The Hg spiking efficiency was compared by impregnating metallic and halogen materials that have high affinity for Hg into activated carbon (AC) to determine an accurate spiking method for Hg on AC. The Hg spiking efficiency was compared according to the type and content of the impregnated substances. AC impregnated with Cl and Au had a 15-20% higher Hg spiking efficiency compared to virgin AC. For Au impregnation at weight ratios of 0-20 wt% of adsorbent, spiking efficiencies of over 97% were observed under certain conditions. The Hg adsorption properties of the above adsorbent were determined experimentally, and the results were used to test the adsorption performance of Hg adsorption traps. PMID- 27684593 TI - Depletion of pentachlorophenol in soil microcosms with Byssochlamys nivea and Scopulariopsis brumptii as detoxification agents. AB - Pentachlorophenol (PCP) is a toxic compound which is widely used as a wood preservative product and general biocide. It is persistent in the environment and has been classified as a persistent organic pollutant to be reclaimed in many countries. Fungal bioremediation is an emerging approach to rehabilitating areas fouled by recalcitrant xenobiotics. In the present study, we isolated two fungal strains from an artificially PCP-contaminated soil during a long-term bioremediation study and evaluated their potential as bioremediation agents in depletion and detoxification of PCP in soil microcosms. The two fungal strains were identified as: Byssochlamys nivea (Westling, 1909) and Scopulariopsis brumptii (Salvanet-Duval, 1935). PCP removal and toxicity were examined during 28 days of incubation. Bioaugmented microcosms revealed a 60% and 62% PCP removal by B. nivea and S. brumptii, respectively. Co-inoculation of B. nivea and S. brumptii showed a synergetic effect on PCP removal resulting in 95% and 80% PCP decrease when initial concentrations were 12.5 and 25 mg kg-1, respectively. Detoxification in bioaugmented soil and the efficient role of fungi in the rehabilitation of PCP contaminated soil were experimentally proven by toxicity assays. A decrease in inhibition of bioluminescence of Escherichia coli HB101 pUCD607 and an increase of germination index of mustard (Brassica alba) seeds were observed in the decontaminated soils. PMID- 27684594 TI - Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay. AB - Retinoic acid (RA) is an important developmental morphogen that coordinates anteroposterior and dorsoventral axis patterning, somitic differentiation, neurogenesis, patterning of the hindbrain and spinal cord, and the development of multiple organ systems. Due to its chemical nature as a small amphipathic lipid, direct detection and visualization of RA histologically remains technically impossible. Currently, methods used to infer the presence and localization of RA make use of reporter systems that detect the biological activity of RA. Most established reporter systems, both transgenic mice and cell lines, make use of the highly potent RA response element (RARE) upstream of the RAR-beta gene to drive RA-inducible expression of reporter genes, such as beta-galactosidase or luciferase. The transgenic RARE-LacZ mouse is useful in visualizing spatiotemporal changes in RA signaling especially during embryonic development. However, it does not directly measure overall RA levels. As a reporter system, the F9 RARE-LacZ cell line can be used in a variety of ways, from simple detection of RA to quantitative measurements of RA levels in tissue explants. Here we describe the quantitative determination of relative RA levels generated in embryos and neurosphere cultures using the F9 RARE-LacZ reporter cell line. PMID- 27684595 TI - Measuring Granulocyte and Monocyte Phagocytosis and Oxidative Burst Activity in Human Blood. AB - The granulocyte and monocyte phagocytosis and oxidative burst (OB) activity assay can be used to study the innate immune system. This manuscript provides the necessary methodology to add this assay to an exercise immunology arsenal. The first step in this assay is to prepare two aliquots ("H" and "F") of whole blood (heparin). Then, dihydroethidium is added to the H aliquot, and both aliquots are incubated in a warm water bath followed by a cold water bath. Next, Staphylococcus aureus (S. aureus) is added to the H aliquot and fluorescein isothiocyanate-labeled S. aureus is added to the F aliquot (bacteria:phagocyte = 8:1), and both aliquots are incubated in a warm water bath followed by a cold water bath. Then, trypan blue is added to each aliquot to quench extracellular fluorescence, and the cells are washed with phosphate-buffered saline. Next, the red blood cells are lysed, and the white blood cells are fixed. Finally, a flow cytometer and appropriate analysis software are used to measure granulocyte and monocyte phagocytosis and OB activity. This assay has been used for over 20 years. After heavy and prolonged exertion, athletes experience a significant but transient increase in phagocytosis and an extended decrease in OB activity. The post-exercise increase in phagocytosis is correlated with inflammation. In contrast to normal weight individuals, granulocyte and monocyte phagocytosis is chronically elevated in overweight and obese participants, and is modestly correlated with C-reactive protein. In summary, this flow cytometry-based assay measures the phagocytosis and OB activity of phagocytes and can be used as an additional measure of exercise- and obesity-induced inflammation. PMID- 27684596 TI - Renal sympathetic stimulation in patients with controlled hypertension and paroxysmal atrial fibrillation. PMID- 27684597 TI - Takotsubo Syndrome: Does it matter if you have diabetes mellitus? PMID- 27684598 TI - Low ankle brachial index is associated with the magnitude of impaired walking endurance in patients with heart failure. AB - BACKGROUND: Measurement of the ankle brachial index (ABI) is a simple, noninvasive means of diagnosing peripheral arterial disease, and has been shown to be associated with mortality rate. Here, we examined the association between ABI and physical function in patients with heart failure (HF). METHODS: The study population consisted of 524 admitted patients (67.2+/-13.9years, 343 males) with HF. Blood pressure and the ABI were determined by oscillometry. Prior to hospital discharge, ABI, 6-minute walking distance, walking velocity, handgrip strength, quadriceps isometric strength, and standing balance were determined. The 524 patients were divided according to ABI as follows: ABI<=0.90 (low ABI), ABI 0.91 to 0.99 (borderline ABI), and ABI 1.00 to 1.40 (normal ABI). RESULTS: Lower ABI values were associated with shorter 6-minute walking distance (p trend=0.001), slower walking velocity (p trend=0.023), and poorer standing balance (p trend=0.048). There were no significant associations between ABI and handgrip strength or quadriceps isometric strength. After adjusting for potential confounders, patients with ABI<=0.90 had shorter 6-minute walking distance compared to those with ABI 1.00 to 1.40 (adjusted mean value: 344m vs. 395m, respectively, p<0.001). There were no significant differences in any of the other physical function parameters examined. CONCLUSIONS: In patients with HF, low ABI is associated with the magnitude of impairment in walking endurance. PMID- 27684599 TI - Kounis syndrome due to antibiotics: A global overview from pharmacovigilance databases. AB - BACKGROUND: Kounis syndrome (KS) is characterized by concurrent presence of anaphylactic and cardiac components. Available evidence suggests that antibiotics are frequently associated to KS. We therefore analyzed KS cases associated with antibiotics use from the two largest pharmacovigilance databases. METHODS: Two pharmacovigilance databases, EudraVigilance and VigiLyze, were searched for cases reporting the adverse reaction "Kounis Syndrome" with antibiotics as suspected active substance. We analyzed the period from December 1st, 2001 to February 16th, 2016. For the most reported active substance, proportional reporting ratio (PRR) was calculated. RESULTS: A total of 10 cases of KS associated with antibiotic use were retrieved from EudraVigilance database. Mean patients' age was 58.2years and 70% were male. The most frequently reported suspected antibiotic was the combination amoxicillin/clavulanic acid (four cases). VigiLyze database reported 13 KS cases associated to antibiotics. Mean age was 56years and 61% of patients were male. The most frequently reported antibiotic was again the combination amoxicillin/clavulanic acid (five cases). Seven duplicate cases were identified, leaving a total of 16 cases of KS, with six of them associated to amoxicillin/clavulanic acid use. The PRR value for amoxicillin/clavulanic acid against other kinds of antibiotics was 2.62 considering EudraVigilance data and 1.61 considering VigiLyze data. CONCLUSIONS: This analysis provided a complete picture of the cases of KS associated with antibiotic use and identified a possible association between amoxicillin/clavulanic acid and KS. Since the number of cases is low, especially considering its wide use, further analyses are needed to confirm the association. PMID- 27684600 TI - Effects of Sulfidation, Magnetization, and Oxygenation on Azo Dye Reduction by Zerovalent Iron. AB - Applications of zerovalent iron (ZVI) for water treatment under aerobic conditions include sequestration of metals (e.g., in acid mine drainage) and decolorization of dyes (in wastewaters from textile manufacturing). The processes responsible for contaminant removal can be a complex mixture of reduction, oxidation, sorption, and coprecipitation processes, which are further complicated by the dynamics of oxygen intrusion, mixing, and oxide precipitation. To better understand such systems, the removal of an azo dye (Orange I) by micron-sized granular ZVI at neutral pH was studied in open (aerobic) stirred batch reactors, by measuring the kinetics of Orange I decolorization and changes in "geochemical" properties (DO, Fe(II), and Eh), with and without two treatments that might improve the long-term performance of this system: sulfidation by pretreatment with sulfide and magnetization by application of a weak magnetic field (WMF). The results show that the changes in solution chemistry are coupled to the dynamics of oxygen intrusion, which was modeled as analogous to dissolved oxygen sag curves. Both sulfidation and magnetization increased Orange I removal rates 2.4 71.8-fold, but there was little synergistic benefit to applying both enhancements together. Respike experiments showed that the enhancement from magnetization carries over from magnetization to sulfidation, but not the reverse. PMID- 27684601 TI - Ocean acidification affects parameters of immune response and extracellular pH in tropical sea urchins Lytechinus variegatus and Echinometra luccunter. AB - The rising concentration of atmospheric CO2 by anthropogenic activities is changing the chemistry of the oceans, resulting in a decreased pH. Several studies have shown that the decrease in pH can affect calcification rates and reproduction of marine invertebrates, but little attention has been drawn to their immune response. Thus this study evaluated in two adult tropical sea urchin species, Lytechinus variegatus and Echinometra lucunter, the effects of ocean acidification over a period of 24h and 5days, on parameters of the immune response, the extracellular acid base balance, and the ability to recover these parameters. For this reason, the phagocytic capacity (PC), the phagocytic index (PI), the capacity of cell adhesion, cell spreading, cell spreading area of phagocytic amebocytes in vitro, and the coelomic fluid pH were analyzed in animals exposed to a pH of 8.0 (control group), 7.6 and 7.3. Experimental pH's were predicted by IPCC for the future of the two species. Furthermore, a recovery test was conducted to verify whether animals have the ability to restore these physiological parameters after being re-exposed to control conditions. Both species presented a significant decrease in PC, in the pH of coelomic fluid and in the cell spreading area. Besides that, Echinometra lucunter showed a significant decrease in cell spreading and significant differences in coelomocyte proportions. The recovery test showed that the PC of both species increased, also being below the control values. Even so, they were still significantly higher than those exposed to acidified seawater, indicating that with the re establishment of the pH value the phagocytic capacity of cells tends to restore control conditions. These results demonstrate that the immune system and the coelomic fluid pH of these animals can be affected by ocean acidification. However, the effects of a short-term exposure can be reversible if the natural values are re-established. Thus, the effects of ocean acidification could lead to consequences for pathogen resistance and survival of these sea urchin species. PMID- 27684602 TI - Content of biogenic amines in Lemna minor (common duckweed) growing in medium contaminated with tetracycline. AB - Aquatic plants are continuously exposed to a variety of stress factors. No data on the impact of antibiotics on the biogenic amines in duckweed (Lemna minor) have been available so far, and such data could be significant, considering the ecological role of this plant in animal food chains. In the tissues of control (non-stressed) nine-day-old duckweed, the following biogenic amines were identified: tyramine, putrescine, cadaverine, spermidine and spermine. Based on the tetracycline contents and the computed EC values, the predicted toxicity units have been calculated. The obtained results demonstrated phytoxicity caused by tetracycline in relation to duckweed growth rate, yield and the contents of chlorophylls a and b. The carotenoid content was not modified by tetracycline. It was found that tetracycline as a water pollutant was a stress factor triggering an increase in the synthesis of amines. Tetracycline at 19, 39 and 78MUM concentrations increased biogenic amine synthesis by 3.5 times. Although the content of tyramine increased fourteen times with the highest concentration of the drug (and of spermidine - only three-fold) the increase of spermidine was numerically the highest. Among the biogenic amines the most responsive to tetracycline were spermine and tyramine, while the least affected were putrescine and spermidine. Despite putrescine and spermidine being the least sensitive, their sum of contents increased five-fold compared to the control. These studies suggest that tetracycline in water reservoirs is taken up by L. minor as the antibiotic clearly modifies the metabolism of this plant and it may likely pose a risk. PMID- 27684604 TI - Genetic analysis of emerging risk factors in coronary artery disease. AB - BACKGROUND AND AIMS: Type 2 diabetes (T2D), low-density lipoprotein-cholesterol (LDL-c), body mass index (BMI), blood pressure and smoking are established risk factors that play a causal role in coronary artery disease (CAD). Numerous common genetic variants associating with these and other risk factors have been identified, but their association with CAD has not been comprehensively examined in a single study. Our goal was to comprehensively evaluate the associations of established and emerging risk factors with CAD using genetic variants identified from Genome-wide Association Studies (GWAS). METHODS: We tested the effect of 60 traditional and putative risk factors with CAD, using summary statistics obtained in GWAS. We approximated the regression of a response variable onto an additive multi-SNP genetic risk score in the Coronary Artery DIsease Genomewide Replication And Meta-analysis (CARDIoGRAM) consortium dataset weighted by the effect of the SNP on the risk factors. RESULTS: The strongest association with risk of CAD was for LDL-c SNPs (p = 3.96E-34). For non-established CAD risk factors, we found significant CAD associations for coronary artery calcification (CAC), Lp(a), LP-PLA2 activity, plaque, vWF and FVIII. In an attempt to identify independent associations between risk factors and CAD, only SNPs with an effect on the target trait were included. This identified CAD associations for Lp(a)(p = 1.77E-21), LDL-c (p = 4.16E-06), triglycerides (TG) (p = 1.94E-05), height (p = 2.06E-05), CAC (p = 3.13E-23) and carotid plaque (p = 2.08E-05). CONCLUSIONS: We identified SNPs associated with the emerging risk factors Lp(a), TG, plaque, height and CAC to be independently associated with risk of CAD. This provides further support for-ongoing clinical trials of Lp(a) and TG, and suggests that CAC and plaque could be used as surrogate markers for CAD in clinical trials. PMID- 27684603 TI - Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end of-season results. AB - The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17. PMID- 27684606 TI - Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies. AB - BACKGROUND AND AIMS: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years). METHODS: Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique. RESULTS: We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%); and ten were replicated in ULSAM (p < 0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease. CONCLUSIONS: The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability. PMID- 27684605 TI - Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes. AB - BACKGROUND AND AIMS: We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. METHODS: In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. RESULTS: We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels >= 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], pfor trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT >= 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). CONCLUSIONS: Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. PMID- 27684607 TI - Probing the influence of unconscious fear-conditioned visual stimuli on eye movements. AB - Efficient threat detection from the environment is critical for survival. Accordingly, fear-conditioned stimuli receive prioritized processing and capture overt and covert attention. However, it is unknown whether eye movements are influenced by unconscious fear-conditioned stimuli. We performed a classical fear conditioning procedure and subsequently recorded participants' eye movements while they were exposed to fear-conditioned stimuli that were rendered invisible using interocular suppression. Chance-level performance in a forced-choice-task demonstrated unawareness of the stimuli. Differential skin conductance responses and a change in participants' fearfulness ratings of the stimuli indicated the effectiveness of conditioning. However, eye movements were not biased towards the fear-conditioned stimulus. Preliminary evidence suggests a relation between the strength of conditioning and the saccadic bias to the fear-conditioned stimulus. Our findings provide no strong evidence for a saccadic bias towards unconscious fear-conditioned stimuli but tentative evidence suggests that such an effect may depend on the strength of the conditioned response. PMID- 27684608 TI - How "mere" is the mere ownership effect in memory? Evidence for semantic organization processes. AB - Memory is better for items arbitrarily assigned to the self than for items assigned to another person (mere ownership effect, MOE). In a series of six experiments, we investigated the role of semantic processes for the MOE. Following successful replication, we investigated whether the MOE was contingent upon semantic processing: For meaningless stimuli, there was no MOE. Testing for a potential role of semantic elaboration using meaningful stimuli in an encoding task without verbal labels, we found evidence of spontaneous semantic processing irrespective of self- or other-assignment. When semantic organization was manipulated, the MOE vanished if a semantic classification task was added to the self/other assignment but persisted for a perceptual classification task. Furthermore, we found greater clustering of self-assigned than of other-assigned items in free recall. Taken together, these results suggest that the MOE could be based on the organizational principle of a "me" versus "not-me" categorization. PMID- 27684609 TI - When the dissolution of perceived body boundaries elicits happiness: The effect of selflessness induced by a body scan meditation. AB - Drawing on the Self-centeredness/Selflessness Happiness Model (SSHM), we hypothesized that a reduction in the salience of perceived body boundaries would lead to increase optimal emotional experience. These constructs were assessed by means of self-report measures. Participants (n=53) were randomly assigned to either the selflessness (induced by a body scan meditation) condition or the control condition. As expected, the reduction in perceived body salience was greater in the body scan meditation condition than in the control condition. The change in perceived body salience was accompanied by a change in happiness and anxiety. Participants in the body-scan meditation condition reported greater happiness and less anxiety than participants in the control condition. Happiness increased when the salience of body boundaries decreased. Mediation analyses reveal that the change in happiness was mediated by the change in perceived body boundaries, which suggests that selflessness elicits happiness via dissolution of perceived body boundaries. PMID- 27684611 TI - Health Informatics in the Public Health 3.0 Era: Intelligence for the Chief Health Strategists. PMID- 27684610 TI - Life priorities in the HIV-positive Asians: a text-mining analysis in young vs. old generation. AB - HIV/AIDS is one of the most urgent and challenging public health issues, especially since it is now considered a chronic disease. In this project, we used text mining techniques to extract meaningful words and word patterns from 45 transcribed in-depth interviews of people living with HIV/AIDS (PLWHA) conducted in Taipei, Beijing, Shanghai, and San Francisco from 2006 to 2013. Text mining analysis can predict whether an emerging field will become a long-lasting source of academic interest or whether it is simply a passing source of interest that will soon disappear. The data were analyzed by age group (45 and older vs. 44 and younger). The highest ranking fragments in the order of frequency were: "care", "daughter", "disease", "family", "HIV", "hospital", "husband", "medicines", "money", "people", "son", "tell/disclosure", "thought", "want", and "years". Participants in the 44-year-old and younger group were focused mainly on disease disclosure, their families, and their financial condition. In older PLWHA, social supports were one of the main concerns. In this study, we learned that different age groups perceive the disease differently. Therefore, when designing intervention, researchers should consider to tailor an intervention to a specific population and to help PLWHA achieve a better quality of life. Promoting self management can be an effective strategy for every encounter with HIV-positive individuals. PMID- 27684612 TI - Control of the Public Health IT Physical Infrastructure: Findings From the 2015 Informatics Capacity and Needs Assessment Survey. AB - BACKGROUND: Despite improvements in information technology (IT) infrastructure in public health, there is still much that can be done to improve the adoption of IT in state and local health departments, by better understanding the impact of governance and control structures of physical infrastructure. OBJECTIVE: To report out the current status of the physical infrastructure control of local health departments (LHDs) and to determine whether there is a significant association between an LHD's governance status and control of the physical infrastructure components. DESIGN: Data came from the 2015 Informatics Capacity and Needs Assessment Survey, conducted by Georgia Southern University in collaboration with the National Association of County and City Health Officials. PARTICIPANTS: A total of 324 LHDs from all 50 states completed the survey (response rate: 50%). MAIN OUTCOME MEASURE(S): Outcome measures included control of LHD physical infrastructure components. Predictors of interest included LHD governance category. RESULTS: The majority of the control of the physical infrastructure components in LHDs resides in external entities. The type of governance structure of the LHD is significantly associated with the control of infrastructure. CONCLUSIONS: Additional research is needed to determine best practices in IT governance and control of physical infrastructure for public health. PMID- 27684614 TI - Electronic Health Records and Meaningful Use in Local Health Departments: Updates From the 2015 NACCHO Informatics Assessment Survey. AB - BACKGROUND: Electronic health records (EHRs) are evolving the scope of operations, practices, and outcomes of population health in the United States. Local health departments (LHDs) need adequate health informatics capacities to handle the quantity and quality of population health data. PURPOSE: The purpose of this study was to gain an updated view using the most recent data to identify the primary storage of clinical data, status of data for meaningful use, and characteristics associated with the implementation of EHRs in LHDs. METHODS: Data were drawn from the 2015 Informatics Capacity and Needs Assessment Survey, which used a stratified random sampling design of LHD populations. Oversampling of larger LHDs was conducted and sampling weights were applied. Data were analyzed using descriptive statistics and logistic regression in SPSS. RESULTS: Forty-two percent of LHDs indicated the use of an EHR system compared with 58% that use a non-EHR system for the storage of primary health data. Seventy-one percent of LHDs had reviewed some or all of the current systems to determine whether they needed to be improved or replaced, whereas only 6% formally conducted a readiness assessment for health information exchange. Twenty-seven percent of the LHDs had conducted informatics training within the past 12 months. LHD characteristics statistically associated with having an EHR system were having state or centralized governance, not having created a strategic plan related to informatics within the past 2 years throughout LHDs, provided informatics training in the past 12 months, and various levels of control over decisions regarding hardware allocation or acquisition, software selection, software support, and information technology budget allocation. CONCLUSION: A focus on EHR implementation in public health is pertinent to examining the impact of public health programming and interventions for the positive change in population health. PMID- 27684615 TI - Strengthening Local Health Department Informatics Capacity Through Advocacy, Education, and Workforce Development. PMID- 27684613 TI - Clinical Data Systems to Support Public Health Practice: A National Survey of Software and Storage Systems Among Local Health Departments. AB - CONTEXT: Numerous software and data storage systems are employed by local health departments (LHDs) to manage clinical and nonclinical data needs. Leveraging electronic systems may yield improvements in public health practice. However, information is lacking regarding current usage patterns among LHDs. OBJECTIVE: To analyze clinical and nonclinical data storage and software types by LHDs. DESIGN: Data came from the 2015 Informatics Capacity and Needs Assessment Survey, conducted by Georgia Southern University in collaboration with the National Association of County and City Health Officials. PARTICIPANTS: A total of 324 LHDs from all 50 states completed the survey (response rate: 50%). MAIN OUTCOME MEASURES: Outcome measures included LHD's primary clinical service data system, nonclinical data system(s) used, and plans to adopt electronic clinical data system (if not already in use). Predictors of interest included jurisdiction size and governance type, and other informatics capacities within the LHD. Bivariate analyses were performed using chi and t tests. RESULTS: Up to 38.4% of LHDs reported using an electronic health record (EHR). Usage was common especially among LHDs that provide primary care and/or dental services. LHDs serving smaller populations and those with state-level governance were both less likely to use an EHR. Paper records were a common data storage approach for both clinical data (28.9%) and nonclinical data (59.4%). Among LHDs without an EHR, 84.7% reported implementation plans. CONCLUSIONS: Our findings suggest that LHDs are increasingly using EHRs as a clinical data storage solution and that more LHDs are likely to adopt EHRs in the foreseeable future. Yet use of paper records remains common. Correlates of electronic system usage emerged across a range of factors. Program- or system-specific needs may be barriers or facilitators to EHR adoption. Policy makers can tailor resources to address barriers specific to LHD size, governance, service portfolio, existing informatics capabilities, and other pertinent characteristics. PMID- 27684616 TI - Interoperability of Information Systems Managed and Used by the Local Health Departments. AB - BACKGROUND: In the post-Affordable Care Act era marked by interorganizational collaborations and availability of large amounts of electronic data from other community partners, it is imperative to assess the interoperability of information systems used by the local health departments (LHDs). OBJECTIVES: To describe the level of interoperability of LHD information systems and identify factors associated with lack of interoperability. DATA AND METHODS: This mixed methods research uses data from the 2015 Informatics Capacity and Needs Assessment Survey, with a target population of all LHDs in the United States. A representative sample of 650 LHDs was drawn using a stratified random sampling design. A total of 324 completed responses were received (50% response rate). Qualitative data were used from a key informant interview study of LHD informatics staff from across the United States. Qualitative data were independently coded by 2 researchers and analyzed thematically. Survey data were cleaned, bivariate comparisons were conducted, and a multivariable logistic regression was run to characterize factors associated with interoperability. RESULTS: For 30% of LHDs, no systems were interoperable, and 38% of LHD respondents indicated some of the systems were interoperable. Significant determinants of interoperability included LHDs having leadership support (adjusted odds ratio [AOR] = 3.54), control of information technology budget allocation (AOR = 2.48), control of data systems (AOR = 2.31), having a strategic plan for information systems (AOR = 1.92), and existence of business process analysis and redesign (AOR = 1.49). CONCLUSION: Interoperability of all systems may be an informatics goal, but only a small proportion of LHDs reported having interoperable systems, pointing to a substantial need among LHDs nationwide. PMID- 27684617 TI - Local Health Departments' Partners and Challenges in Electronic Exchange of Health Information. AB - BACKGROUND: Unprecedented amounts of data are produced by the health care and other sectors, presenting opportunities for local health departments (LHDs) to access these data. LHDs will need to participate in health information exchange (HIE) with a number of partners in order to benefit from these data resources. LHDs' participation in HIEs with specific partners has not been studied. OBJECTIVES: To describe the level of and challenges in LHD participation in HIE with other partners, and variation by LHD population size and governance type. DATA AND METHODS: This research uses data from the 2015 Informatics Capacity and Needs Assessment Survey, with a target population of all LHDs in the United States. A representative sample of 650 LHDs was drawn using a stratified random sampling design. A total of 324 completed responses were received with a 50% response rate. Survey data were cleaned, and bivariate comparisons were conducted using chi and Somer's D. RESULTS: Substantial variation existed in LHDs' participation in HIE by type of exchange partner. Although 71% participated in HIE with the state departments of health, only 12% with jail/correctional health, 14% with health or county-based purchasing plans, and 15% with home health agencies. Compared with large LHDs (jurisdiction populations of >=500 000), smaller LHDs were more likely to participate in HIE with state departments of health, but less likely with other exchange partners. The challenges to HIE participation were technological, and organizational/interorganizational in nature and variation existed by LHDs' population size and governance structure with respect to state authority. CONCLUSIONS: Local public health agencies more commonly participate in HIE with some partners, but may need to improve HIE with many others. National strategies targeting an increase in HIE of LHDs may use our findings to focus those initiatives. PMID- 27684618 TI - Assessing Skills and Capacity for Informatics: Activities Most Commonly Performed by or for Local Health Departments. AB - OBJECTIVE: To describe the informatics activities performed by and for local health departments. DESIGN: Analysis of data from the 2015 Informatics Capacity and Needs Assessment Survey of local health departments conducted by the Jiann Ping Hsu College of Public Health at Georgia Southern University in collaboration with the National Association of County & City Health Officials. PARTICIPANTS: 324 local health departments. MAIN OUTCOME MEASURE(S): Informatics activities performed at or for local health departments in use and analysis of data, system design, and routine use of information systems. RESULTS: A majority of local health departments extract data from information systems (69.5%) and use and interpret quantitative (66.4%) and qualitative (55.1%) data. Almost half use geographic information systems (45.0%) or statistical or other analytical software (39.7%). Local health departments were less likely to perform project management (35.8%), business process analysis and redesign (24.0%), and developing requirements for informatics system development (19.7%). Local health departments were most likely to maintain or modify content of a Web site (72.1%). A third of local health departments (35.8%) reported acting as "super users" for their information systems. A significantly higher proportion of local health departments serving larger jurisdictions (500 000+) and those with shared governance reported conducting informatics activities. CONCLUSION: Most local health department informatics activities are completed by local health department staff within each department or a central department, but many state health departments also contribute to informatics at the local level. Larger local health departments and those with shared governance were more likely to perform informatics activities. Local health departments need effective leadership, a skilled workforce, strong partnerships, and policies that foster implementation of health information systems to successfully engage in informatics. Local health departments also face important training needs, including data analytics, project management, and geographical information systems, so they can adapt to the increasing availability of electronic data and changes in technology. PMID- 27684619 TI - Public Health Staff Development Needs in Informatics: Findings From a National Survey of Local Health Departments. AB - CONTEXT: Public health practice is information-intensive and information-driven. Public health informatics is a nascent discipline, and most public health practitioners lack necessary skills in this area. OBJECTIVE: To describe the staff development needs of local health departments (LHDs) related to informatics. DESIGN: Data came from the 2015 Informatics Capacity and Needs Assessment Survey, conducted by Georgia Southern University in collaboration with the National Association of County & City Health Officials. PARTICIPANTS: A total of 324 LHDs from all 50 states completed the survey (response rate: 50%). MAIN OUTCOME MEASURE(S): Outcome measures included LHDs' specific staff development needs related to informatics. Predictors of interest included jurisdiction size and governance type. RESULTS: Areas of workforce development and improvement in informatics staff of LHDs included using and interpreting quantitative data, designing and running reports from information systems, using and interpreting qualitative data, using statistical or other analytical software, project management, and using geographical information systems. Significant variation in informatics training needs exists depending on the size of the LHD population and governance type. CONCLUSION: Substantial training needs exist for LHDs across many areas of informatics ranging from very basic to specialized skills and are related to the size of LHD population and governance type. PMID- 27684620 TI - Urgent Challenges for Local Public Health Informatics. PMID- 27684621 TI - Investigating Informatics Activity, Control, and Training Needs in Large, Medium, and Small Health Departments. AB - INTRODUCTION: A recent National Association of City & County Health Officials survey shed light on informatics workforce development needs. Local health departments (LHDs) of various jurisdictional sizes and control over informatics may differ on training needs and activity. Understanding the precise nature of this variation will allow stakeholders to appropriately develop workforce development tools to advance the field. OBJECTIVE: To understand the informatics training needs for LHDs of different jurisdictional sizes. METHODS: Survey responses were analyzed by comparing training needs and LHD population size. RESULTS: Larger health departments consistently reported having greater informatics-related capacity and informatics-related training needs. Quantitative data analysis was identified as a primary need for large LHDs. In addition, LHDs that report higher control of informatics/information technology were able to engage in more informatics activities. CONCLUSION: Smaller LHDs need additional resources to improve informatics-related capacity and engagement with the field. PMID- 27684622 TI - Assessment of Local Health Department Utility of Syndromic Surveillance: Results of the 2015 Biosurveillance Needs Assessment Survey. PMID- 27684623 TI - Workforce Competencies in Syndromic Surveillance Practice at Local Health Departments. AB - CONTEXT: As the science and practice of syndromic surveillance (SyS) evolve, it has increasing utility for public health surveillance at the local level. Local health departments (LHDs) require specific organizational and workforce capabilities to use SyS data. In 2013, more than half of the LHDs reported using SyS, although little has been reported about LHD workforce capabilities in SyS. OBJECTIVE: To conduct an assessment of self-reported knowledge and skills in SyS tasks to effectively target technical assistance to different levels of LHD need. DESIGN, SETTING, AND PARTICIPANTS: A stratified sampling design based on LHD jurisdiction population and SyS status was employed. Data were drawn from the 2015 Biosurveillance Needs Assessment Survey, which captured variables related to LHD use of SyS, management of systems, and self-reported proficiencies in a typology of SyS functionalities developed by a workgroup of subject matter experts in SyS. Respondents were US-based LHD public health practitioners. Estimation weights were applied during analysis to determine the national representation of the responses. MAIN OUTCOME MEASURES: Respondents self-reported proficiency in 26 SyS tasks within 5 categories, analyzed by LHD jurisdiction size and respondents' years of SyS experience. RESULTS: SyS expertise varied widely across LHDs. Less than 50% of workers who have access to SyS demonstrated overall proficiency within any of the task areas: communication, data use, data analysis, quality monitoring and assurance, and system design and development. SyS users were strongest in data use tasks. Proficiency in SyS practice corresponded directly with respondents' years of SyS experience and the LHD jurisdiction size. CONCLUSION: SyS practitioners display a wide range of proficiencies both within and across SyS tasks. Considerable gaps in proficiencies of all areas of SyS practice indicate a need for technical assistance and knowledge dissemination to improve SyS practice as an important component of an LHD surveillance strategy. PMID- 27684625 TI - Informatics as a Strategic Priority and Collaborative Processes to Build a Smarter, Forward-Looking Health Department. PMID- 27684624 TI - Accomplishments and Opportunities in Biosurveillance. PMID- 27684626 TI - Using Information Systems to Improve a Mid-Sized Local Health Department's Effectiveness in a Time of Rapid Change. AB - BACKGROUND: Informatics capacity building is resource and personnel intensive. Many local health departments (LHDs) face tradeoffs between using their resources to carry out existing mandates and using resources to build their capacity, for example, through informatics, to deliver essential services in a more effective and efficient manner. OBJECTIVE: The purpose of this case study is to describe how a mid-sized LHD built and used information systems to support its strategic objectives, clinical services, and surveillance. METHODS: The mid-sized LHD described here was chosen for its "best practices" in informatics capacity building and use by NACCHO's study advisory committee. To conduct the case study, authors reviewed departmental documents and conducted semistructured interviews with key informants in the agency. Interviews were recorded, transcribed, thematically coded, and analyzed. RESULTS AND CONCLUSIONS: Findings from the case study suggest that including capacity building in informatics as a strategic priority is one of the most effective ways to ensure that informatics are assessed, updated, and included in resource decisions. Leadership at all levels is critical to the successful implementation of informatics as is proactive partnership with community partners who have overlapping goals. The efficiency and effectiveness of LHDs rely on informatics capacity, especially when resources are challenged. PMID- 27684627 TI - The Methods Behind 2015 Informatics Capacity and Needs Assessment Study. AB - The 2015 Informatics Needs and Capacity of Local Health Departments (LHDs) survey is the most recent comprehensive source of quantitative data on LHD informatics. Conducted by the National Association of County & City Health Officials (NACCHO), this is the third nationally representative quantitative study of LHD informatics since 2009. The previous 2 comprehensive quantitative assessments were conducted by NACCHO in 2009-2010 and 2011. Given that public health informatics is rapidly evolving, the 2015 Informatics survey is a much-needed country-wide assessment of the current informatics needs and capacities of LHDs. This article outlines detailed methodology used in the 2015 Informatics survey, including instrument development, pretesting, sampling design and sample size, survey administration, and sampling weights. A 9-member advisory committee representing federal, state, and local health agency representatives guided the design and implementation of this study. The survey instrument was organized into 6 topic areas: demographics, physical infrastructure, skills and capacity available, public health workforce development needs, electronic health records, and health information exchange. The instrument was pretested with a sample of 20 LHDs and subsequently pilot tested with 30 LHDs. The survey was administered via the Qualtrics survey software to the sample of 650 LHDs, selected using stratified random sampling. The survey was fielded for approximately 8 weeks and 324 usable responses were received, constituting a response rate of 50%. Statistical weights were developed to account for 3 factors: (a) disproportionate response rate by population size (using 7 population strata), (b) oversampling of LHDs with larger population sizes, and PMID- 27684628 TI - An Iterative, Low-Cost Strategy to Building Information Systems Allows a Small Jurisdiction Local Health Department to Increase Efficiencies and Expand Services. AB - OBJECTIVE AND METHODS: The objective of this case study was to describe the process and outcomes of a small local health department's (LHD's) strategy to build and use information systems. The case study is based on a review of documents and semi-structured interviews with key informants in the Pomperaug District Health Department. Interviews were recorded, transcribed, coded, and analyzed. RESULTS AND CONCLUSIONS: The case study here suggests that small LHDs can use a low-resource, incremental strategy to build information systems for improving departmental effectiveness and efficiency. Specifically, we suggest that the elements for this department's success were simple information systems, clear vision, consistent leadership, and the involvement, training, and support of staff. PMID- 27684629 TI - Factors Influencing Quality of Life Six Months after a First-Ever Ischemic Stroke: Focus on Thrombolyzed Patients. AB - OBJECTIVE: This prospective follow-up study aimed to identify sociodemographic and clinical factors that may affect the quality of life (QoL) of patients with acute ischemic stroke during a 6-month follow-up. PATIENTS AND METHODS: In the acute phase, sociodemographic and clinical data were collected using the National Institute of Health Stroke Scale, Barthel Index, and modified Rankin Scale. QoL was assessed with the Stroke and Aphasia Quality of Life Scale-39 6 months after stroke. RESULTS: QoL was evaluated in 64 patients (aged 45-81 years) with a first ever ischemic stroke. Thrombolytic therapy was given to 80% of the patients. Stroke severity, dependence in activities of daily living, degree of handicap, and length of hospitalization were associated with QoL. QoL was not associated with age, gender, marital status, or years of education. CONCLUSION: In this study, most patients were treated with thrombolysis, and QoL results resembled those of earlier studies on patients without thrombolysis. Despite good physical recovery, the patients reported impairments in QoL. QoL assessments can give clinicians a more holistic picture of stroke recovery from the patient's perspective. PMID- 27684630 TI - Co-culture of Living Microbiome with Microengineered Human Intestinal Villi in a Gut-on-a-Chip Microfluidic Device. AB - Here, we describe a protocol to perform long-term co-culture of multi-species human gut microbiome with microengineered intestinal villi in a human gut-on-a chip microphysiological device. We recapitulate the intestinal lumen-capillary tissue interface in a microfluidic device, where physiological mechanical deformations and fluid shear flow are constantly applied to mimic peristalsis. In the lumen microchannel, human intestinal epithelial Caco-2 cells are cultured to form a 'germ-free' villus epithelium and regenerate small intestinal villi. Pre cultured microbial cells are inoculated into the lumen side to establish a host microbe ecosystem. After microbial cells adhere to the apical surface of the villi, fluid flow and mechanical deformations are resumed to produce a steady state microenvironment in which fresh culture medium is constantly supplied and unbound bacteria (as well as bacterial wastes) are continuously removed. After extended co-culture from days to weeks, multiple microcolonies are found to be randomly located between the villi, and both microbial and epithelial cells remain viable and functional for at least one week in culture. Our co-culture protocol can be adapted to provide a versatile platform for other host-microbiome ecosystems that can be found in various human organs, which may facilitate in vitro study of the role of human microbiome in orchestrating health and disease. PMID- 27684631 TI - The Value of Traditions New and Old. PMID- 27684632 TI - The Effect of Warm Water Intake on Bowel Movements in the Early Postoperative Stage of Patients Having Undergone Laparoscopic Cholecystectomy: A Randomized Controlled Trial. AB - This study was aimed at determining the effect of oral administration of warm water during the postoperative initial stage on the time of first flatus in patients who had undergone laparoscopic cholecystectomy. In the literature, it is emphasized that warm water has favorable effects on intestinal movements such as "reliving gastrointestinal spasms and helping peristalsis return." This randomized controlled trial and experimental study was conducted in a university hospital between May and December 2011. In the study sample, we included a total of 60 patients; 30 were in the experimental group (drank warm water), while the other 30 composed the control group. Patients were randomized through a simple random sampling method. The experimental group was provided with 200 ml of warm water at 98.6 degrees F (37 degrees C) in the fourth postoperative hour and were made to drink it within 15 minutes. Patients received no oral intake other than warm water until the eighth postoperative hour. The oral feeding of both groups started in the eighth postoperative hour with fluids and soft food. They shifted to the normal diet as tolerated. In the analysis of the data and percentage numbers, chi-square test and Fisher's exact test, Student's t test, Mann-Whitney U test, Kruskal-Wallis variance, and correlation analysis were used. The results of the data were considered reliable and statistically significant when they were in the reliability interval of 95% and p < .05. No significant differences were found between the patients in the experimental and control groups in terms of demographic features, bowel habits, surgery durations, postoperative applications, nausea/vomiting conditions, and initial mobilization times (p > .05). Groups were homogeneously distributed. Flatus expulsion in the experimental group was 11 +/- 4.2 hours and was determined to be 18.6 +/- 6 hours for patients in the control group (p < .05); in contrast, no significant difference was detected in terms of the times of stool defecation (p > .05). It was determined that warm water intake in the fourth postoperative hour significantly decreased the first flatus expulsion period and had a favorable impact on intestinal movements. PMID- 27684633 TI - Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn. AB - This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific. PMID- 27684634 TI - The Effects of a Self-Care Program on the Severity of Symptoms and Quality of Life of Patients With Irritable Bowel Syndrome. AB - Irritable bowel syndrome (IBS) is a chronic disease that needs special self-care strategies. The current study aimed at determining the effects of a self-care program on the severity of symptoms and quality of life of patients with IBS. In this randomized controlled clinical trial, 119 patients were randomly assigned to the experimental (n = 60) and control (n = 59) groups. Patients in both groups received the usual treatment of IBS by a gastroenterologist. The control group did not receive any intervention, whereas the experimental group was trained in the self-care program. The process of implementing the self-care program included designing and determining the content validity of the self-care training package, individual training, the first follow-up call, group training, and the second follow-up call. The instruments for collecting data were IBS-Quality of Life and IBS-Symptom Severity Scale. Two sets of evaluations (before and 2 months after the intervention) were done for both groups. The data were analyzed using SPSS software, Version 16. The results showed that there was not a significant difference between the two groups in the severity of symptoms and quality of life before the intervention (p > .05); however, the 2 groups were significantly different after the intervention (p < .0001). Implementation of the self-care program resulted in the improvement of quality of life and reduction in the symptom severity in the experimental group after the intervention (p < .0001), whereas no significant changes were observed in the control group (p > .05). Hence, the data supports that self-care program was effective in improving the quality of life and reducing the severity of symptoms in patients with IBS. PMID- 27684635 TI - Supportive Communication to Facilitate Chinese Patients' Adaptation to a Permanent Colostomy: A Qualitative Case Study Approach. AB - This study, which is a part of action research, aims to explore how supportive communication can impact individuals' adaptation to a permanent colostomy in a Chinese cultural context. Two Chinese rectal cancer patients with complexity and difficulty in living with a permanent colostomy were selected using a qualitative case study approach. The researcher (H.T.) interacted with the participants along their journey from the preoperative period until the third postoperative month after discharge via face-to-face or telephone interviews. Content analysis was applied. Supportive communication was characterized by "communication as a supportive tool," which consisted of 4 elements: respect, description, empathy, and empowerment. The nursing strategies included (1) developing a collaborative relationship with patients and families; (2) understanding patients' concerns and problems; (3) discussing potential solutions; (4) encouraging patients to take action; (5) bringing out emotional expression; (6) normalizing negative emotions; and (7) protecting hope. The findings of this study informed that supportive communication is a valuable tool for nurses to provide informational and emotional support to Chinese patients in order to enhance their adaptation to living with a permanent colostomy. Developing an operational manual to enhance supportive communication for patients with colostomy is suggested. PMID- 27684636 TI - Clinical Application of Prophylactic Ethanol Lock Therapy in Pediatric Patients With Intestinal Failure. AB - Patients with intestinal failure have an increased risk for catheter-related bloodstream infections that can necessitate central venous line replacement and result in morbidity, prolonged hospitalization, or mortality. For pediatric patients with intestinal failure, the severe loss of intestinal absorptive ability leads to reliance on parenteral nutrition to meet minimal needs required for growth and development. Reliance on parenteral nutrition, in turn, forces dependency on central venous lines. Recent research concentrating on the pediatric population with intestinal failure indicates that prophylactic ethanol lock therapy can reduce the rate of catheter-related bloodstream infections and decrease central venous line removal rates in this high-risk population. Prevention of catheter-related bloodstream infections is critical for patients with intestinal failure. Ethanol lock therapy policies and protocols are increasingly being developed in healthcare institutions. Despite these efforts, no standard guidelines currently exist for ethanol lock therapy, and research in this area, specifically involving the pediatric population, is limited. This article presents the evidence to date as a means for assisting nursing professionals to make informed clinical decisions regarding the use of ethanol lock therapy for pediatric patients with intestinal failure. PMID- 27684637 TI - Evaluation of a Self-Management Program for Gastroesophageal Reflux Disease in China. AB - Gastroesophageal reflux disease is a chronic disease with a high incidence worldwide. The various symptoms have substantial impact on the quality of life of affected individuals. A long-term self-management program can increase the ability of patients to make behavioral changes, and health outcomes can improve as a consequence. This study's aim was to evaluate the effectiveness of a self management program for gastroesophageal reflux disease. A total of 115 patients with gastroesophageal reflux disease were allocated to the experimental group and the control group. The former received self-management intervention along with conventional drug therapy, whereas the latter received standard outpatient care and conventional drug therapy. After the clinical trial, the control group also received the same self-management intervention. The levels of self-management behaviors, self-efficacy, gastroesophageal reflux disease symptoms, and psychological condition were compared. Those in the experimental group demonstrated significantly higher self-efficacy for managing their illness, showed positive changes in self-management behaviors, and had comparatively better remission of symptoms and improvement in psychological distress. The program helped patients with gastroesophageal reflux disease self-manage their illness as possible. PMID- 27684638 TI - GASTROINTESTINAL STROMAL TUMOR IN A YOUNG MAN WITH SEVERE HEMATEMESIS: A CASE STUDY. PMID- 27684639 TI - ENDOSCOPIC OR SURGICAL INTERVENTION FOR PAINFUL OBSTRUCTIVE CHRONIC PANCREATITIS. PMID- 27684640 TI - STANDARDS OF INFECTION PREVENTION IN REPROCESSING FLEXIBLE GASTROINTESTINAL ENDOSCOPES. PMID- 27684642 TI - Influenza Vaccination Coverage Among Health Care Personnel - United States, 2015 16 Influenza Season. AB - The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all health care personnel to reduce influenza-related morbidity and mortality among both health care personnel and their patients (1-4). To estimate influenza vaccination coverage among U.S. health care personnel for the 2015-16 influenza season, CDC conducted an opt-in Internet panel survey of 2,258 health care personnel during March 28-April 14, 2016. Overall, 79.0% of survey participants reported receiving an influenza vaccination during the 2015-16 season, similar to the 77.3% coverage reported for the 2014-15 season (5). Coverage in long-term care settings increased by 5.3 percentage points compared with the previous season. Vaccination coverage continued to be higher among health care personnel working in hospitals (91.2%) and lower among health care personnel working in ambulatory (79.8%) and long-term care settings (69.2%). Coverage continued to be highest among physicians (95.6%) and lowest among assistants and aides (64.1%), and highest overall among health care personnel who were required by their employer to be vaccinated (96.5%). Among health care personnel working in settings where vaccination was neither required, promoted, nor offered onsite, vaccination coverage continued to be low (44.9%). An increased percentage of health care personnel reporting a vaccination requirement or onsite vaccination availability compared with earlier influenza seasons might have contributed to the overall increase in vaccination coverage during the past 6 influenza seasons. PMID- 27684643 TI - The Trade-off Between Speed and Safety in Drug Approvals. PMID- 27684644 TI - Identified key genes related to carotid atheroma plaque from gene expression chip. AB - As one of the leading reason in morbidity and death in the world, atherosclerosis is usually associated with vessel stenosis, ulceration, and inflammatory cell infiltration. However, the formation mechanism of atheroma plaque is unknown. In this research, we have used bioinformatics tools to identify 118 differential expression genes from a GEO dataset. Besides, we also revealed KYNU as a crucial gene in atheroma plaque development. PMID- 27684645 TI - Investing Wisely in Health Care Capital. PMID- 27684646 TI - Experience theory, or How desserts are like losses. AB - Although many experiments have explored risk preferences for money, few have systematically assessed risk preferences for everyday experiences. We propose a conceptual model and provide convergent evidence from 7 experiments to suggest that, in contrast to a typical "zero" reference point for choices on money, reference points for choices of experiences are set at more extreme outcomes, leading to concave utility for negative experiences but convex utility for positive experiences. As a result, people are more risk-averse for negative experiences such as disgusting foods-as for monetary gains-but more risk-seeking for positive experiences such as desserts-as for monetary losses. These risk preferences for experiences are robust to different methods of elicitation. (PsycINFO Database Record PMID- 27684647 TI - From disruptive to standard - making next-generation sequencing reliable: an interview with Christophe Roos. PMID- 27684649 TI - Emotion regulation strategies in daily life: mindfulness, cognitive reappraisal and emotion suppression. AB - Most empirical studies of emotion regulation have relied on retrospective trait measures, and have not examined the link between daily regulatory strategies and every day emotional well-being. We used a daily diary methodology with multilevel modelling data analyses (n = 187) to examine the influence of three emotion regulation strategies (mindfulness, cognitive reappraisal and emotion suppression) on the experience of daily negative and positive affect. Our results suggested that daily mindfulness was associated with lower negative and higher positive affect whereas the converse pattern was found for daily emotion suppression; cognitive reappraisal was related to daily positive, but not negative affect. When daily mindfulness, suppression and reappraisal were included in the same models, these strategies predicted unique variance in emotional well-being. Random slope analyses revealed substantial variability in the utility of these strategies. Indeed the presumably "adaptive" cognitive reappraisal strategy seemed to confer no benefit to the regulation of negative affect in approximately half the sample. Additional analyses revealed that age moderates the effect of cognitive reappraisal on daily negative affect: Higher use of reappraisal was associated with more negative affect for adolescents (aged 17 to 19) but became associated with less negative affect with increasing age. We interpret these results in line with a contextual view of emotion regulation where no strategy is inherently "good" or "bad". PMID- 27684648 TI - Multicenter immunoassay validation of cerebrospinal fluid neurofilament light: a biomarker for neurodegeneration. AB - AIM: Neurofilament light (NfL) chain, a putative cerebrospinal fluid biomarker, can support neurodegenerative disease diagnosis and indicate disease severity and prognosis. Universal validation protocols when used to measure biomarkers can reduce pre and analytical laboratory variation, thus increasing end-user confidence in the consistency of validation data across sites. METHODOLOGY: Here, a commercially available NfL ELISA (UmanDiagnostics, Umea, Sweden) was validated in a multicentered setting using comprehensive newly developed standard operating procedures. RESULTS: The data showed good assay sensitivity and intra and interassay precision. Interlaboratory precision was, however, suboptimal. CONCLUSION: The UmanDiagnostics assay is suitable for the quantification of NfL in human cerebrospinal fluid. However, sources of interlaboratory variation in the data require further investigation. PMID- 27684651 TI - Triangulated Proxy Reporting: a technique for improving how communication partners come to know people with severe cognitive impairment. AB - PURPOSE: This paper explains and demonstrates the pilot application of Triangulated Proxy Reporting (TPR); a practical technique for enhancing communication around people who have severe cognitive impairment (SCI). METHODS AND RESULTS: An introduction explains SCI and how this impacts on communication; and consequently on quality of care and quality of life. This is followed by an explanation of TPR and its origins in triangulation research techniques. An illustrative vignette explicates its utility and value in a group home for a resident with profound multiple disabilities. The Discussion and Conclusion sections propose the wider application of TPR for different cohorts of people with SCIs, their communication partners and service providers. CONCLUSIONS: TPR presents as a practical technique for enhancing communication interactions with people who have SCI. The paper demonstrates the potential of the technique for improving engagement amongst those with profound multiple disabilities, severe acquired brain injury and advanced dementia and their partners in and across different care settings. Implications for Rehabilitation Triangulated Proxy Reporting (TPR) shows potential to improve communications between people with severe cognitive impairments and their communication partners. TPR can lead to improved quality of care and quality of life for people with profound multiple disabilities, very advanced dementia and severe acquired brain injury, who otherwise are very difficult to support. TPR is a relatively simple and inexpensive technique that service providers can incorporate into practice to improving communications between clients with severe cognitive impairments, their carers and other support professionals. PMID- 27684650 TI - Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis. AB - Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-alpha, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERbeta remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality. PMID- 27684652 TI - Diffusible signal factor-dependent quorum sensing in pathogenic bacteria and its exploitation for disease control. AB - Cell-to-cell signals of the diffusible signal factor (DSF) family are cis-2 unsaturated fatty acids of differing chain length and branching pattern. DSF signalling has been described in diverse bacteria to include plant and human pathogens where it acts to regulate functions such as biofilm formation, antibiotic tolerance and the production of virulence factors. DSF family signals can also participate in interspecies signalling with other bacteria and interkingdom signalling such as with the yeast Candida albicans. Interference with DSF signalling may afford new opportunities for the control of bacterial disease. Such strategies will depend in part on detailed knowledge of the molecular mechanisms underlying the processes of signal synthesis, perception and turnover. Here, I review both recent progress in understanding DSF signalling at the molecular level and prospects for translating this knowledge into approaches for disease control. PMID- 27684655 TI - 'All the evidence points to a severe nursing shortage, but still government departments insist there is no crisis'. AB - Personnel managers in three NHS regions have set up taskforces to tackle the recruitment crisis which has hit the nursing profession. Birmingham went on 'yellow alert' last month, not because of a shortage of money or beds, but because there weren't enough nurses. Successive reports throughout the year have highlighted the need for skilled staff in intensive care, theatres and neonatal care. It is now estimated that some L8 million is spent in trying to recruit nurses.'All the evidence points to a severe nursing shortage, hut still government departments insist there is no crisis.' PMID- 27684654 TI - Premorbid adjustment in individuals at ultra-high risk for developing psychosis: a case-control study. AB - AIM: Deterioration in premorbid adjustment is related to ultra-high risk (UHR) individuals developing psychosis, but it has not been examined how UHR individuals' development differs compared to healthy controls. This study investigates differences in premorbid adjustment between UHR individuals and a healthy control group. METHOD: A total of 48 UHR individuals and 50 healthy controls matched on group level for age, gender and parents' socio-economic status were included in the study. Both groups were assessed with the Premorbid Adjustment Scale (PAS). Based on the PAS scores, composite social and academic scales were computed. RESULTS: Compared to the healthy controls the UHR individuals' social and academic premorbid adjustment declined across age periods. Social premorbid adjustment declined particularly between late adolescence and adulthood. Academic premorbid adjustment declined particularly between childhood and early adolescence. The UHR individuals had more premorbid adjustment difficulties on both the social and academic scale, and on the individual PAS scales. CONCLUSION: From childhood UHR individuals have lower levels of social and academic premorbid adjustment compared to healthy controls, and the difficulties increase with age. As such, social and academic premorbid adjustment could be an important focus for early intervention. PMID- 27684653 TI - When to perform preoperative chest computed tomography for renal cancer staging. AB - OBJECTIVES: To provide objective criteria for preoperative staging chest computed tomography (CT) in patients diagnosed with renal cell carcinoma (RCC) because, in the absence of established indications, the decision for preoperative chest CT remains subjective. PATIENTS AND METHODS: A total of 1 946 patients undergoing surgical treatment of RCC, whose data were collected in a prospective institutional database, were assessed. The outcome of the study was presence of pulmonary metastases at staging chest CT. A multivariable logistic regression model predicting positive chest CT was fitted. Predictors consisted of preoperative clinical tumour (cT) and nodal (cN) stage, presence of systemic symptoms and platelet count (PLT)/haemoglobin (Hb) ratio. RESULTS: The rate of positive chest CT was 6% (n = 119). At multivariable logistic regression, >=cT1b, cN1, systemic symptoms and Hb/PLT ratio were all associated with higher risk of positive chest CT (all P < 0.001). After 2000-sample bootstrap validation, the concordance index was found to be 0.88. At decision-curve analysis, the net benefit of the proposed strategy was superior to the select-all and select-none strategies. Accordingly, if chest CT had been performed when the risk of a positive result was >1%, a negative chest CT would have been spared in 37% of the population and a positive chest CT would have been missed in 0.2% of the population only. CONCLUSIONS: The proposed strategy estimates the risk of positive chest CT at RCC staging with optimum accuracy and the results were statistically and clinically relevant. The findings of the present study support a recommendation for chest CT in patients with >=cT1b, cN1, systemic symptoms or anaemia and thrombocythemia. Conversely, in patients with cT1a, cN0 without systemic symptoms, anaemia and thrombocythemia, chest CT could be omitted. PMID- 27684656 TI - ? AB - Sign of the times: a temporary staff agency in London's Oxford Street responds to recent evidence that nurses are leaving the profession to take up administrative posts. PMID- 27684657 TI - Dorrell says pay dispute worthwhile. AB - Health secretary Stephen Dorrell insists the nine month 1995 pay dispute was worth the effort, despite almost all nurses receiving exactly the same increase. PMID- 27684658 TI - Nurse shortages across the UK as holiday season approaches. AB - Trusts are bracing themselves for a new year of nursing shortages as recruitment problems spread from specialties into general nursing and from London to the rest of the UK. PMID- 27684660 TI - Concern over increase in injuries due to wheelie bins. AB - Nurses in West Yorkshire are dealing with a new health hazard - fractures caused by the use of wheelie bins. PMID- 27684661 TI - Cumberlege criticises TV programme for 'alarmist' report on cot death. AB - Junior health minister Baroness Cumberlege has slammed the TV programme The Cook Report as 'alarmist' after experts found no link between cot deaths and the emission of toxic gases from cot mattresses. PMID- 27684662 TI - ? AB - The Health Education Authority has launched a campaign aimed at encouraging women not to smoke during pregnancy after its researchers found 29 per cent of pregnant women do not give up. PMID- 27684663 TI - Industrial action closer as Scottish trust insists on changes to grades. AB - Nurses ac a community and mental health trust were preparing for a Christmas dispute over management plans to make sweeping changes to grades and staffing. PMID- 27684664 TI - Unions meet government over final details of 1995 pay deal. AB - A consensus to end the prolonged negotiations over the 1995 nurses' pay award was being discussed as Nursing Standard went to press. PMID- 27684665 TI - ? AB - Walking tall: Two casualties of land-mines in Afghanistan learning to walk with artificial limbs, pictured in the The State of the World's Children, the 50th anniversary report of UNICEF. More than I million people have been killed by exploding landmines since 1975, with 800 civilians dying each month. PMID- 27684667 TI - RCN tells 'Scrooge' trusts to pay up. AB - The Royal College of Nursing has accused 'Scrooge' trusts of spoiling Christmas for nurses by refusing to offer them a fair pay award. PMID- 27684668 TI - Plans to cut spending on red tape receive mixed response. AB - Government plans to slash L130 million from the health service management bill have received a mixed welcome from nursing unions. PMID- 27684669 TI - Liberal democrats claim health cuts are likely. AB - Government claims to have increased health spending for 1995-6 by 0.6 per cent 'in real terms', in line with the Conservatives' 1992 manifesto pledge, are misleading, the Liberal Democrats have said. PMID- 27684670 TI - NHS employers' bodies to change. AB - The two main organisations representing NHS employers are set to be disbanded and replaced by two new bodies. PMID- 27684671 TI - Patient deaths in mental hospitals 'not investigated'. AB - A third of the deaths of patients detained under the Mental Health Act are never investigated, a report from the Mental Health Foundation charity claims. PMID- 27684674 TI - Primary care nurses' role in continence. AB - Brief training for primary care nurses in assessment and management of incontinence can have long term benefits for women, researchers report. PMID- 27684672 TI - Efficacy of smoking cessation strategies. AB - Neither high-dose nicotine replacement therapy nor intensive counselling seem to increase smoking cessation rates beyond those of lower doses and brief counselling. PMID- 27684673 TI - Stress adversely affects wound healing. AB - Psychological stress can adversely affect wound healing, which could have important clinical implications, according to researchers from Ohio. PMID- 27684675 TI - Nurses' stress caring for organ donors. AB - Nurses caring for organ donors and their families want stress debriefing sessions and more education on grief and coping theories, according to a nurse researcher. PMID- 27684676 TI - Review of the year 1995. PMID- 27684677 TI - Traumas and tests in the great outdoors. AB - There I was, abseiling down a 60ft: cliff to rescue a critically injured geologist while three RAF fighter jets screamed overhead - and I was earning 30 Continuing Education points at the same time. PMID- 27684678 TI - Express delivery. AB - It is against the law in this country for anyone other than a midwife or a registered medical practitioner to contract with a woman to deliver her baby ( 1 ). It is not unknown, however, for babies to arrive suddenly, without allowing enough time for the midwife to arrive or the woman to get to a hospital in time for the contract to be fulfilled. It is only in a case of sudden or urgent necessity' that an exception is made. PMID- 27684679 TI - The challenge of change. AB - The Nursing Update learning unit and six weekly articles in the Continuing Education series which comprise the third Clinical Practice and Management Awards series are all on management topics and are presented in relation to clinical cameos. The aim is to help nurses in clinical practice understand management, an approach which enables nurses and managers to work together to achieve the best practice within the available resources. PMID- 27684680 TI - How to use instant relaxation methods. AB - Nurses are only too familiar with the stress component of illness. The need to soothe a patient's fears and relieve the anxiety which invariably accompanies illness of any sort is well recognised. Many nurses have also studied methods of relieving stress including cognitive restructuring, social skills and relaxation training. PMID- 27684681 TI - Introducing training for care assistants. AB - National vocational qualifications (NVQs) are based upon national standards determined by representatives from employer organisations, unions, and education and training providers. The framework for NVQs is centred on the assumption that students gain knowledge and experience which makes them competent to carry out their role. NVQs are, therefore, composed of a number of units of competence. The units contain performance criteria against which the candidate is assessed and they also outline the knowledge that the candidate is expected to demonstrate. PMID- 27684682 TI - Bionursing: signs 3 of iron deficiency. AB - In the ninth article in our series on bionursing, the authors explain bow an undo standing of physiology can help nurses to identify the common signs and symptoms of iron deficiency and ensure patients receive prompt and appropriate treatment. PMID- 27684684 TI - Happy in a challenging job. AB - Many articles in the nursing press focus on dissatisfaction. But I am in the fortunate position of enjoying my job. I work as a research nurse for an intensive care unit specialising in areas such as acute liver failure, liver transplant, acute renal failure, paediatrics and acute respiratory distress syndrome. PMID- 27684683 TI - Time for some real answers on flu jab. AB - Is anyone else concerned about the flu vaccine and its promotion? PMID- 27684685 TI - Principles behind good communication. AB - Every nurse appreciates the importance of good communication. The job relies on it. Not long ago it was about building relationships with colleagues, patients and their relatives to ensure good care. Now the advent of the purchaser/provider arrangement and the marketing of service in the NHS has changed that. PMID- 27684686 TI - Running a nursing home - hard work and little money. AB - What an excellent article 'Nursing home nightmare' was (Viewpoint November 22). What a shame the author preferred to remain anonymous. It is true that market competition means nursing home owners do not confide in each other or leak information to the lcxal press, but it is high time they did. PMID- 27684687 TI - Freemasons are good citizens too. AB - In his letter 'Masonry viewed as anti-Christian' (Letters November 15), Dr Killey shows that he does not know much about Freemasonry. PMID- 27684688 TI - Don't misrepresent counsellors. AB - I would like to protest at the way counselling and counsellors are sometimes portrayed. A case in point was the November 15 cover of Nursing Standard. PMID- 27684689 TI - Consultants must begin to change. AB - I agree with your article about nurses and junior doctors' hours when it says consultants must change (Beat the Clock, Features December 6). PMID- 27684690 TI - Nursing standard a hit among younger readers! AB - Since the age of two my daughter Lynette has shown a great interest in my work as a staff nurse and enjoyed coming to visit me at my work as much as possible. PMID- 27684691 TI - First aid, not life support. AB - I was disappointed by 'Training which saves lives' (Newsfile November 29), in which the writer portrays Andrew Kent as a pioneer in training firefighters in advanced life support. How can this man, in a matter of days, train anyone in advanced life support? PMID- 27684693 TI - Down memory lane. AB - Doing battle with the off-duty - and the staff who all want to work the same shifts. PMID- 27684692 TI - Round the reforms. PMID- 27684694 TI - The gospel truth. AB - Christmas proved something of a public relations disaster for King I lerod. For 2,000 years his reaction to news of the birth of the King of the Jews has been condemned as impetuous and a trifle excessive. PMID- 27684695 TI - Conference characters. AB - The nursing' conference has become a year- round fixture. At one time, conferences were limited to that slot in summer known as the 'sillyseason'. Now you can go to one every week. The titles cover every subject known to nursing, from acupressure to underwater birthing, from politics to esoteric nursing theory, but there are a number of features common to all. For example, there are the conference titles. No organiser likes to limit the speakers and this leads to noncommittal conference titles, such as Nursing Towards 2000 and Health Care: The Way Forward. PMID- 27684696 TI - Fair provision. AB - With winter's arrival my thoughts turn to those affected by sickle cell disorders. One of the most common problems for people suffering from this inherited blood disorder is the painful 'crisis' that accounts for over 90 per cent of their admissions to hospital and which can be triggered by cold weather. PMID- 27684697 TI - Help yourself. AB - Christmas is a time for celebrations, feasting and rejoicing. It's a time when over indulgence in rich food is accepted as the norm. My thoughts at this time turn towards the Asian diabetic patient for whom religious festivities are common and where sweet and rich foods form an important part of what is eaten. PMID- 27684698 TI - Equal access. AB - As nurse coordinator at Manchester's Chinese Health Information Centre, Mary Tso Kam Ha believes permanent mainstream funding is essential if she is to achieve her goal of a stable, well orientated service for this long established community. PMID- 27684699 TI - The great quest for leadership. AB - There is certainly a new imperative for leadership, not just in nursing or in the United Kingdom. The greatest call in business and politics throughout the western world is one for leadership. Even the NHS is slowly waking up to the need for less management and more leadership. So what makes a good leader? The professional literature is disappointingly sparse on the issue but there are massive amounts from industry, academia, the media and business - especially from the United States. The following attributes are by no means exhaustive but they come up again and again in the literature. PMID- 27684700 TI - A programme for nursing leadership. AB - Two years ago, the Royal College of Nursing set up a 'Nurses in Leadership' project to address the fact that despite many calls to develop and encourage nurse leaders, nurses continue to be under-represented in senior positions compared with other disciplines. PMID- 27684702 TI - Listing. PMID- 27684701 TI - Leadership: the hidden dangers. AB - Irrespective of the reasons for assuming a leadership role, the responsibility will have a significant impact on everyday life, sometimes beneficial and sometimes detrimental. The positive effects of occupying a leadership position are easy to see. Nothing breeds success like success, which in turn gives rise to increased enthusiasm and contentment. Others may experience the energy, pride and satisfaction and most will derive pleasure from their contribution to success, with a consequent increase in motivation. The success may be accompanied by public acclaim such as awards, publications and recognition within the organisation. PMID- 27684703 TI - Testing the status-legitimacy hypothesis: A multilevel modeling approach to the perception of legitimacy in income distribution in 36 nations. AB - The status-legitimacy hypothesis was tested by analyzing cross-national data about social inequality. Several indicators were used as indexes of social advantage: social class, personal income, and self-position in the social hierarchy. Moreover, inequality and freedom in nations, as indexed by Gini and by the human freedom index, were considered. Results from 36 nations worldwide showed no support for the status-legitimacy hypothesis. The perception that income distribution was fair tended to increase as social advantage increased. Moreover, national context increased the difference between advantaged and disadvantaged people in the perception of social fairness: Contrary to the status legitimacy hypothesis, disadvantaged people were more likely than advantaged people to perceive income distribution as too large, and this difference increased in nations with greater freedom and equality. The implications for the status-legitimacy hypothesis are discussed. PMID- 27684704 TI - Correction: Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice. AB - [This corrects the article DOI: 10.1371/journal.pone.0153835.]. PMID- 27684707 TI - Development of a decision aid for children faced with the decision to undergo dental treatment with sedation or general anaesthesia. AB - BACKGROUND: Decision aids are tools used to help individuals faced with difficult healthcare decisions. They help patients further understand the treatment options available and encourage the sharing of information between patients and clinicians. AIM: To develop a decision aid for young patients faced with the decision to undergo dental treatment with inhalation sedation, intravenous sedation, or general anaesthesia (GA). DESIGN: Qualitative interviews with dental patients (aged 10-16 years), and their parents/guardians were used to inform the content of a draft decision aid. Following further revisions, a pilot evaluation of the decision aid was conducted. Patients referred for dental treatment with sedation or GA were recruited from a UK dental hospital. Patients (n = 15) and parents/guardians (n = 13) assigned to the intervention group received the decision aid and routine clinical counselling, whereas patients (n = 17) and parents/guardians (n = 13) in the control group only received routine clinical counselling. Participants completed measures of knowledge, decisional conflict, and dental anxiety. RESULTS: Knowledge scores were significantly higher for participants who received the decision aid when compared to standard care. There were no other significant differences between groups. CONCLUSIONS: A decision aid was successfully developed, and initial findings suggest such tools could be beneficial to dental sedation or GA patients and their parents/guardians. Further research is required on the use of such tools in primary care settings, with particular attention to the impact of the decision aid on attendance and completion rates of treatment. PMID- 27684706 TI - Shark Conservation: An Educational Approach Based on Children's Knowledge and Perceptions toward Sharks. AB - Shark conservation has become a focus of current international conservation efforts. However, the misunderstanding of sharks and their negative public portrayal may hinder their conservation. More importantly, the consumption of shark fin, which is very common in Chinese cultures, poses a significant threat to sharks. Hong Kong has long been the world's largest shark fin trading center. Shark conservation would become more sustainable if public understanding of this predatory fish and an appreciation of its ecological significance could be promoted. It is possible that the demand for fins could be effectively managed through long-term educational efforts targeted at younger generations. To provide essential baseline data for planning of these educational efforts, this project investigated the perceptions of 11 to 12 year-old primary school students in Hong Kong about sharks, and their understanding of ecological concepts and shark related knowledge. The findings indicate that these students lack sufficient knowledge and possess misconceptions about sharks and their ecological significance in the marine ecosystem. The students' conceptual understanding level is strongly correlated with their perceptions. Correlational analyses further demonstrated a positive association between formal education and perceptions toward shark conservation. The students who favoured shark fin consumption did so because of its tastiness, whereas concerns about shark population decline and the cruelty of shark hunting were the main reasons for not favoring shark fin consumption. This pilot study provides preliminary but important insights into primary school education regarding the conservation of sharks. PMID- 27684708 TI - Myasthenia Gravis Manifesting As Head Drop in an Elderly Adult with Parkinson's Disease. PMID- 27684705 TI - "Obesity Paradox" in Acute Respiratory Distress Syndrome: Asystematic Review and Meta-Analysis. AB - BACKGROUND: It is unclear whether an "obesity paradox" exists in the respiratory system, especially in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Previous studies have postulated a causal relation between obesity and ARDS/ALI but have lacked power to form a definitive conclusion. OBJECTIVE: To investigate the relationships between obesity, ARDS/ALIrisk, and mortality. METHODS: A systematic search current to April 2016 was performed in Pubmed, EMBASE, Medline, Cochrane databases to find relevant studies. All studies that estimate the effect of obesity in the morbidity and mortality of ARDS/ALI were included. RESULTS: A total of 24 studies including 9,187,248 subjects were analyzed. The combined results from 16 studies that examined the effect of obesity in morbidity of ARDS/ALI showed an89% increase in odds ratio(pooled odds ratios (OR) 1.89, 95% confidence intervals (CI) 1.45 to 2.47). In subgroup analysis, compared to normal weight, obesity was associated with an increased risk of ARDS/ALI (OR1.57, 95% CI 1.30-1.90 for obese (BMI30-39.9kg/m2); OR1.75, 95% CI 1.42-2.15 for obese(BMI>=30kg/m2); OR1.67, 95% CI 1.04-2.68 for morbid obese(BMI>=40kg/m2)). The combined results from 9 studies that examined the effect of obesity in mortality of ARDS/ALI had a pooled odds ratio(pooled OR 0.63, 95% CI 0.41 to 0.98). Inversely, obesity was significantly associated with reduced risk of ARDS/ALI mortality(OR0.88, 95% CI 0.78-1.00 for overweight(BMI<=18.5m2); OR0.74, 95% CI 0.64-0.84 for obese (BMI30 39.9kg/m2);OR0.84, 95% CI 0.75-0.94 for 60days mortality; OR0.38, 95% CI 0.22 0.66 for 90days mortality). CONCLUSIONS: Our data identify obesity as an important risk factor for the development of ARDS/ALI; however, ARDS/ALI outcomes are improved in this population when compared to individuals with a normal body mass index. This meta-analysis results supported ''obesity paradox" in ARDS/ALI. PMID- 27684710 TI - Incidence of and Risk Factors for Pediatric Metachronous Contralateral Inguinal Hernia: Analysis of a 17-Year Nationwide Database in Taiwan. AB - BACKGROUND: Previous prospective, retrospective, and meta-analysis studies revealed that the overall incidence of metachronous contralateral inguinal hernia (MCIH) ranges from 5.76% to 7.3%, but long-term follow-up postoperative data are scant. We identified the incidence and risk factors of MCIH in pediatric patients during the follow-up using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: Between 1996/01/01 and 2008/12/31, all pediatric patients with primary unilateral inguinal hernia repair who were born after 1996/01/01 were collected via ICD-9 diagnostic and procedure codes recorded in NHIRD. Patients with another operation during the same admission, complicated hernia, or laparoscopic procedure were excluded. Several reported risk factors, including age, sex, preterm birth, low body weight, and previous ventriculoperitoneal shunt placement, were used for analysis. The primary endpoint was the repairmen of MCIH following the initial surgery. All patients were followed until 2013/12/31 or withdrawal from national health insurance. RESULTS: A total of 31,100 pediatric patients underwent unilateral inguinal hernia repair, and 111.76 months of median follow-up data were collected. The overall rate of MCIH was 12.3%. Among the 31,100 patients who had the hernia repair, 63.6% had MCIH within 2 years and 91.5% had MCIH within 5 years. After initial surgery, the incidence of MCIH gradually and significantly decreased with age up to approximately 6 years. Multivariable analysis showed that age <4 y and girls were risk factors for subsequent MCIH. CONCLUSIONS: After 17 years of follow-up, the overall MCIH rate was 12.3%, and 91.7% of patients needed repair for MCIH within the first 5 years after initial surgery. Age <4 years and girls were risk factors for MCIH. The contralateral exploration for inguinal hernia should be considered among these patients. PMID- 27684709 TI - Arabidopsis CaM1 and CaM4 Promote Nitric Oxide Production and Salt Resistance by Inhibiting S-Nitrosoglutathione Reductase via Direct Binding. AB - Salt is a major threat to plant growth and crop productivity. Calmodulin (CaM), the most important multifunctional Ca2+ sensor protein in plants, mediates reactions against environmental stresses through target proteins; however, direct proof of the participation of CaM in salt tolerance and its corresponding signaling pathway in vivo is lacking. In this study, we found that AtCaM1 and AtCaM4 produced salt-responsive CaM isoforms according to real-time reverse transcription-polymerase chain reaction analyses; this result was verified based on a phenotypic analysis of salt-treated loss-of-function mutant and transgenic plants. We also found that the level of nitric oxide (NO), an important salt responsive signaling molecule, varied in response to salt treatment depending on AtCaM1 and AtCaM4 expression. GSNOR is considered as an important and widely utilized regulatory component of NO homeostasis in plant resistance protein signaling networks. In vivo and in vitro protein-protein interaction assays revealed direct binding between AtCaM4 and S-nitrosoglutathione reductase (GSNOR), leading to reduced GSNOR activity and an increased NO level. Overexpression of GSNOR intensified the salt sensitivity of cam4 mutant plants accompanied by a reduced internal NO level, whereas a gsnor deficiency increased the salt tolerance of cam4 plants accompanied by an increased internal NO level. Physiological experiments showed that CaM4-GSNOR, acting through NO, reestablished the ion balance to increase plant resistance to salt stress. Together, these data suggest that AtCaM1 and AtCaM4 serve as signals in plant salt resistance by promoting NO accumulation through the binding and inhibition of GSNOR. This could be a conserved defensive signaling pathway in plants and animals. PMID- 27684711 TI - Phylogeny of Elatinaceae and the Tropical Gondwanan Origin of the Centroplacaceae(Malpighiaceae, Elatinaceae) Clade. AB - The flowering plant family Elatinaceae is a widespread aquatic lineage inhabiting temperate and tropical latitudes, including ~35(-50) species. Its phylogeny remains largely unknown, compromising our understanding of its systematics. Moreover, this group is particularly in need of attention because the biogeography of most aquatic plant clades has yet to be investigated, resulting in uncertainty about whether aquatic plants show histories that deviate from terrestrial plants. We inferred the phylogeny of Elatinaceae from four DNA regions spanning 59 accessions across the family. An expanded sampling was used for molecular divergence time estimation and ancestral area reconstruction to infer the biogeography of Elatinaceae and their closest terrestrial relatives, Malpighiaceae and Centroplacaceae. The two genera of Elatinaceae, Bergia and Elatine, are monophyletic, but several traditionally recognized groups within the family are non-monophyletic. Our results suggest two ancient biogeographic events in the Centroplacaceae(Malpighiaceae, Elatinaceae) clade involving western Gondwana, while Elatinaceae shows a more complicated biogeographic history with a high degree of continental endemicity. Our results indicate the need for further taxonomic investigation of Elatinaceae. Further, our study is one of few to implicate ancient Gondwanan biogeography in extant angiosperms, especially significant given the Centroplacaceae(Malpighiaceae, Elatinaceae) clade's largely tropical distribution. Finally, Elatinaceae demonstrates long-term continental in situ diversification, which argues against recent dispersal as a universal explanation commonly invoked for aquatic plant distributions. PMID- 27684712 TI - Mixture of PLA-PEG and biotinylated albumin enables immobilization of avidins on electrospun fibers. AB - The application of nanotechnology in biomedical field has enormous potential in basic and applied research. Micro or nanofibers produced by electrospinning technique offer excellent properties because of large specific surface area, high porosity, and ability to incorporate functional additives. Here we embedded biotinylated bovine serum albumin into polylactic acid (PLA)-polyethylene glycol (PEG) fibers, which enabled specific immobilization of fluorescently labelled avidin. An alkaline phosphatase enzyme was immobilized via biotin-streptavidin interaction on the hybrid nanofibers, demonstrating the suitability of the material for biosensing applications. These functional nanofibers provide a promising platform for development of biosensors and other biofunctional materials utilizing avidin-biotin as a generic and robust immobilization method. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 356-362, 2017. PMID- 27684713 TI - Understanding the meaning of marital relationship quality among couples in peri urban Ethiopia. AB - This study explores the meaning of marital relationship quality (MRQ) among couples in peri-urban Ethiopia. We examined the factor structure of MRQ by assessing the reliability and validity of four validated Western scales capturing domains of trust, commitment, satisfaction and communication through exploratory factor analysis. Although most of the items of the original Western scales were relevant for the study population, the domains did not mirror the original Western scales and varied by gender. Interestingly, while the domains of commitment and trust followed the Western scales and were very similar across gender, the third domain, which we labelled conflict differed by gender. For women, items from the constructive communication scale seemed relevant, indicating an interest in resolving conflicts, whereas for men, items from the satisfaction scale appeared more important, indicating a desire to avoid or reduce conflict in their relationships. Our study highlights the usefulness of adapting existing validated scales in a new context after assessing their psychometric properties. Such applications provide opportunities for broadening understanding of fundamental MRQ domains that may universally be shared cross culturally. PMID- 27684714 TI - Paraptosis-like cell death in Wistar rat granulosa cells. AB - Follicular atresia, a common process present in all mammals, involves apoptotic and autophagic cell death. However, the participation of paraptosis, a type of caspase-independent cell death, during follicular atresia is unknown. This study found swollen endoplasmic reticulum in the granulosa cells of adult Wistar rats. Calnexin was used as a marker of the endoplasmic reticulum at the ultrastructural and optical levels. The cells with swelling of the endoplasmic reticulum were negative to the TUNEL assay and active caspase-3 immunodetection, indicating that this swelling is not part of any apoptotic or autophagic process. Additionally, immunodetection of the CHOP protein was used as a marker of endoplasmic reticulum stress, and this confirmed the presence of the paraptosis process. These data suggest that paraptosis-like cell death is associated with the death of granulosa cells during follicular atresia in adult Wistar rats. PMID- 27684715 TI - Large Genomic Imbalances in Brugada Syndrome. AB - PURPOSE: Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. METHODS: 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). RESULTS: The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. CONCLUSION: CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes. PMID- 27684716 TI - Planning for the worst: estimates of obesity and comorbidities in school-age children in 2025. AB - BACKGROUND: Member states of the World Health Organization have adopted resolutions aiming to achieve 'no increase on obesity levels' by 2025 (based on 2010 levels) for infants, adolescents and adults. OBJECTIVES: We aimed to assess the scale of the problem facing health planners and service providers. METHODS AND RESULTS: Using data prepared by the Global Burden of Disease collaborative for 2000 and 2013, we have estimated that by 2025 some 268 million children aged 5-17 years may be overweight, including 91 million obese, assuming no policy interventions have proven effective at changing current trends. We have also estimated the likely numbers of children in 2025 with obesity-related comorbidities: impaired glucose tolerance (12 million), type 2 diabetes (4 million), hypertension (27 million) and hepatic steatosis (38 million). A supplemental table provides estimates for each of 184 nations. CONCLUSION: The 2025 targets are unlikely to be met, and health service providers will need to plan for a significant increase in obesity-linked comorbidities. PMID- 27684717 TI - Why quality of life measurement is important in dermatology clinical practice: An expert-based opinion statement by the EADV Task Force on Quality of Life. AB - The aim of this study was to describe the many ways in which quality of life (QoL) measurement may potentially be advantageous in routine clinical dermatology practice. Thirteen members of the EADV Task Force on Quality of Life, eight dermatologists, three health psychologists, one epidemiologist and one pharmacoepidemiologist, independently listed all of the ways they thought this may be advantageous. A total of 108 different ways of using QoL information in clinical practice were suggested (median per participant = 8, range = 4-15), and were classified into 20 descriptive groups. These were sorted into the following five categories: inform clinical decisions, clinician-patient communication, awareness of skin disease burden, informing the consultation and clinical service administration. The wide range of potential benefits identified may not only encourage clinicians to use these measures but also highlights many areas requiring evidence to establish the true value of routine use of QoL measures. PMID- 27684718 TI - Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. AB - Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1beta, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC/BPS research. PMID- 27684719 TI - Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma. AB - OBJECTIVES: Epstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18 5p as well as BamHI-W DNA as biomarkers. MATERIALS AND METHODS: Serums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients. RESULTS: The sensitivity/specificity of circulating BamHI-W DNA, miR BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100 / 100, 85 / 85, 60 / 95, and 25 / 100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors. CONCLUSION: The copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17 5p is a potential biomarker of a poor prognosis. PMID- 27684720 TI - Biodegradable and plasma-treated electrospun scaffolds coated with recombinant Olfactomedin-like 3 for accelerating wound healing and tissue regeneration. AB - Three-dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM-related protein Olfactomedin-like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4-fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in-growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds. PMID- 27684721 TI - Assessing the attractive/repulsive force balance in axial cyclohexane C-Hax ...Yax contacts: A combined computational analysis in monosubstituted cyclohexanes. AB - The interactions of axial substituents in monosubstituted cyclohexane rings are studied in this work using an array of different computational techniques. Additionally, the anomalous axial preference for some bulky substituents is related to stabilizing dispersion interactions. We find that the C-Hax ...Yax contacts for various substituents with distances ranging from 2 to ~5 A may include attractive dispersion forces that can affect the conformational equilibrium; these forces co-exist with Pauli repulsive forces effected by Yax group due to van der Waals sphere penetration. At distances between 2 and 3 A stabilizing electron transfer interactions were calculated and the combination of natural bond orbital and QTAIM analysis showed that, in certain cases, Yax = t Bu, Cax -O or Cax = O or Sax = O or Cax = S this interaction can be characterized as an improper H-bond. DFT-D3 and non-covalent interactions calculations (NCIs) in cyclohexane derivatives with Yax = SiOR3 including HYax ...Hcy surfaces at distances ranging between 4 and 6 A suggest that dispersion has a clear effect on the experimentally observed stabilization of the axial conformer. NCIs computed from the reduced density gradient help to visually identify and analyze these interactions. (c) 2016 Wiley Periodicals, Inc. PMID- 27684722 TI - FISH-Based Analysis of Clonally Derived CHO Cell Populations Reveals High Probability for Transgene Integration in a Terminal Region of Chromosome 1 (1q13). AB - A basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. Here, we constructed engineered Chinese hamster ovary cell lines (CHO-S) with a pCHO-hVR1 vector that carried an extracellular domain of a VEGF receptor (VR) fusion gene. Forty-five clones with high hVR1 expression were selected for karyotype analysis. Using fluorescence in situ hybridization (FISH) and G-banding, we found that pCHO hVR1 was integrated into three chromosomes, including chromosomes 1, Z3 and Z4. Four clones were selected to evaluate their productivity under non-fed, non optimized shake flask conditions. The results showed that clones 1 and 2 with integration sites on chromosome 1 revealed high levels of hVR1 products (shake flask of approximately 800 mg/L), whereas clones 3 and 4 with integration sites on chromosomes Z3 or Z4 had lower levels of hVR1 products. Furthermore, clones 1 and 2 maintained their productivity stabilities over a continuous period of 80 generations, and clones 3 and 4 showed significant declines in their productivities in the presence of selection pressure. Finally, pCHO-hVR1 localized to the same region at chromosome 1q13, the telomere region of normal chromosome 1. In this study, these results demonstrate that the integration of exogenous hVR1 gene on chromosome 1, band q13, may create a high protein producing CHO-S cell line, suggesting that chromosome 1q13 may contain a useful target site for the high expression of exogenous protein. This study shows that the integration into the target site of chromosome 1q13 may avoid the problems of random integration that cause gene silencing or also overcome position effects, facilitating exogenous gene expression in CHO-S cells. PMID- 27684723 TI - Trueness and Precision of Four Intraoral Scanners in Oral Implantology: A Comparative in Vitro Study. AB - PURPOSE: The aim of this study was to compare the trueness and precision of four intraoral scanners used in oral implantology. METHODS: Two stone models were prepared, representing a partially and a totally edentulous maxilla, with three and six implant analogues, respectively, and polyether-ether-ketone (PEEK) cylinders screwed on. The models were digitized with an industrial scanner (IScan D104I(r)) used as a reference, and with four intraoral scanners (Trios(r); CS 3500(r); Zfx Intrascan(r); Planscan(r)). Five scans were taken for each model, using each different intraoral scanner. All datasets were loaded into reverse engineering software (Geomagics 2012(r)), where intraoral scans were superimposed on the reference model, to evaluate general trueness, and superimposed on each other within groups, to evaluate general precision. General trueness and precision of any scanner were compared by model type, through an ANOVA model including scanner, model and their interaction. Finally, the distance and angles between simulated implants were measured in each group, and compared to those of the reference model, to evaluate local trueness. RESULTS: In the partially edentulous maxilla, CS 3500(r) had the best general trueness (47.8 MUm) and precision (40.8 MUm), followed by Trios(r) (trueness 71.2 MUm, precision 51.0 MUm), Zfx Intrascan(r) (trueness 117.0 MUm, precision 126.2 MUm), and Planscan(r) (trueness 233.4 MUm, precision 219.8 MUm). With regard to general trueness, Trios(r) was significantly better than Planscan(r), CS 3500(r) was significantly better than Zfx Intrascan(r) and Planscan(r), and Zfx Intrascan(r) was significantly better than Planscan(r); with regard to general precision, Trios(r) was significantly better than Zfx Intrascan(r) and Planscan(r), CS 3500(r) was significantly better than Zfx Intrascan(r) and Planscan(r), and Zfx Intrascan(r) was significantly better than Planscan(r). In the totally edentulous maxilla, CS 3500(r) had the best performance in terms of general trueness (63.2 MUm) and precision (55.2 MUm), followed by Trios(r) (trueness 71.6 MUm, precision 67.0 MUm), Zfx Intrascan(r) (trueness 103.0 MUm, precision 112.4 MUm), and Planscan(r) (trueness 253.4 MUm, precision 204.2 MUm). With regard to general trueness, Trios(r) was significantly better than Planscan(r), CS 3500(r) was significantly better than Zfx Intrascan(r) and Planscan(r), and Zfx Intrascan(r) was significantly better than Planscan(r); with regard to general precision, Trios(r) was significantly better than Zfx Intrascan(r) and Planscan(r), CS 3500(r) was significantly better than Zfx Intrascan(r) and Planscan(r), and Zfx Intrascan(r) was significantly better than Planscan(r). Local trueness values confirmed these results. CONCLUSIONS: Although no differences in trueness and precision were found between partially and totally edentulous models, statistically significant differences were found between the different scanners. Further studies are required to confirm these results. PMID- 27684724 TI - Neuropsychology in Finland - over 30 years of systematically trained clinical practice. AB - OBJECTIVE: The aim of this invited paper for a special issue of international practice in The Clinical Neuropsychologist is to provide information on training models, clinical practice, and professional issues within neuropsychology in Finland. METHOD: Relevant information was gathered via literature searches, a survey by the Neuropsychology Working Group of the Finnish Psychological Association, archives of the Finnish Neuropsychological Society, and personal communication with professionals in Finland. RESULTS: The roots of Finnish neuropsychology are linked to the early German tradition of experimental psychology. Since the 1970s, it has been strongly influenced by both the psychometric approach in the U.S. and the qualitative approach by Luria. Systematic specialization training program began in Finland in 1983. It was first organized by the Finnish Neuropsychological Society and since 1997 by Finnish universities. At present, around 260 neuropsychologists have completed this training. According to the survey by the Finnish Psychological Association in 2014, 67% of Finnish neuropsychologists work in the public sector, 36% in the private sector, and 28% reported that they had private practice. Work includes assessments for 90% of the respondents, rehabilitation for 74%, and many are involved in teaching and research. Of the respondents, 20% worked both with adults and children, 44% with adults only and 36% with children only. Within test development, pediatric neuropsychology is an especially prominent field. CONCLUSIONS: A unique blend of approaches and a solid systematic training tradition has led to a strong position of neuropsychologists as distinguished experts in the Finnish health care system. PMID- 27684726 TI - Pathways of Acetyl-CoA Metabolism Involved in the Reversal of Palmitate-Induced Glucose Production by Metformin and Salicylate. AB - The pathways through which fatty acids induce insulin resistance have been the subject of much research. We hypothesise that by focussing on the reversal of insulin resistance, novel insights can be made regarding the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered during the prevention of palmitate-induced glucose production in hepatocytes using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075 mM, 48 h) with or without metformin (0.25 mM) and sodium salicylate (2 mM) in the final 24 h of palmitate treatment, and effects on glucose production were determined. RNA microarray measurements followed by gene set enrichment analysis were performed to investigate pathway regulation. Lipidomic analysis and measurement of secreted bile acids and cholesterol were also performed. Reversal of palmitate-induced glucose production by metformin and sodium salicylate was characterised by co ordinated down-regulated expression of pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. All 20 enzymes that regulate the conversion of acetyl-CoA to cholesterol were reduced following metformin and sodium salicylate. Selected findings were confirmed using primary mouse hepatocytes. Although total intracellular levels of diacylglycerol, triacylglycerol and cholesterol esters increased with palmitate, these were not, however, further altered by metformin and sodium salicylate. 6 individual diacylglycerol, triacylglycerol and cholesterol ester species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. These results implicate acetyl-CoA metabolism and C18 lipid species as modulators of hepatic glucose production that could be targeted to improve glucose homeostasis. PMID- 27684725 TI - Markers of Subclinical Cardiovascular Disease in Nonfunctional Adrenal Incidentaloma Patients without Traditional Cardiovascular Risk Factors. AB - Introduction: Data regarding cardiovascular risk in patients with non-functional adrenal incidentaloma (NFAI) are limited. The objectives of this study are to investigate markers of subclinical cardiovascular disease like carotid intima media thickness (CIMT), pulse wave velocity (PWV), augmentation index (AIx), soluble CD40 ligand (sCD40L) and leptin levels in NFAI patients without traditional cardiovascular risk factors and healthy control group. Methods: This study involved 35 patients with NFAI (11 males, 24 females; mean age, 52.4+/-7.7 years) and 35 healthy subjects as control group (11 males, 24 females; mean age, 51.8+/-7.2 years). CIMT was evaluated by ultrasonographical methods. PWV and AIx were measured with TensioClinic arteriograph system. Serum leptin and sCD40L levels were measured by ELISA. Results: In NFAI patients group; CIMT (p<0.001), PWV (p<0.001), AIx brachial (p<0.001) and AIx aorta (p=0.008) were found higher than the control group. Cortisol levels after 1mg dexamethasone suppression test (DST) were higher (p=0.006) and DHEASO4 levels were lower (p=0.008) in NFAI patients than control group. We found that CIMT had positive correlation with age (r=0.484, p<0.005), triglycerides (r=0.378, p<0.005) and cortisol level after 1 mg DST (r=0.346, p<0.005); PWV had positive correlation with total cholesterol (r=0.338, p<0.005) triglycerides (r=0.335, p<0.05) and insulin levels (r=0.426, p<0.005); AIx brachial had a positive correlation with triglycerides (r=0414, p<0.05) and negative correlation with DHEASO4 (r=-0.380, p<0.005); leptin levels had a positive correlation with body mass index (r=0.541, p<0.001) and HOMA-IR index. Conclusion: We showed that subjects with NFAI without traditional cardiovascular risk factors featured several disturbances (CIMT, PWV and AIx) compared to the control group that could be attributable to increased cardiovascular risk. PMID- 27684727 TI - A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics. AB - The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is also a valuable model system to test, and to evaluate therapeutics and drugs that negate maladaptive remodeling in the vessel. The injury, or barotrauma, in the vessel lumen caused by an inflated balloon via an inserted catheter induces subsequent neointimal growth, often leading to hyperplasia or thickening of the vessel wall that narrows, or obstructs the lumen. The method described here is sufficiently sensitive, and the results can be obtained in relatively short time (2 weeks after the surgery). The efficacy of the drug or therapeutic against the induced remodeling can be evaluated either by the post-mortem pathological and histomorphological analysis, or by ultrasound sonography in live animals. In addition, this model system has also been used to determine the therapeutic window or the time course of the administered drug. These studies can leadto the development of a better administrative strategy and a better therapeutic outcome. The procedure described here provides a tool for translational studies that bring drug and therapeutic candidates from bench research to clinical applications. PMID- 27684728 TI - Should the diagnosis of COPD be based on a single spirometry test? AB - Clinical guidelines indicate that a chronic obstructive pulmonary disease (COPD) diagnosis is made from a single spirometry test. However, long-term stability of diagnosis based on forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) ratio has not been reported. In primary care subjects at risk for COPD, we investigated shifts in diagnostic category (obstructed/non-obstructed). The data were from symptomatic 40+ years (ex-)smokers referred for diagnostic spirometry, with three spirometry tests, each 12+/-2 months apart. The obstruction was based on post-bronchodilator FEV1/FVC < lower limit of normal (LLN) and <0.70 (fixed ratio). A total of 2,352 subjects (54% male, post bronchodilator FEV1 76.5% predicted) were studied. By LLN definition, 32.2% were obstructed at baseline, but 32.2% of them were no longer obstructed at years 1 and/or 2. By fixed ratio, these figures were 46.6 and 23.8%, respectively. Overall, 14.3% of subjects changed diagnostic category by 1 year and 15.4% by 2 years when applying the LLN cut-off, and 15.1 and 14.6% by fixed ratio. Change from obstructed to non-obstructed was more likely for patients with higher body mass index (BMI) and baseline short-acting bronchodilator (SABA) users, and less likely for older subjects, those with lower FEV1% predicted, baseline inhaled steroid users, and current smokers or SABA users at year 1. Change from non obstructed to obstructed was more likely for males, older subjects, current smokers and patients with lower baseline FEV1% predicted, and less likely for those with higher baseline BMI. Up to one-third of symptomatic (ex-)smokers with baseline obstruction on diagnostic spirometry had shifted to non-obstructed when routinely re-tested after 1 or 2 years. Given the implications for patients and health systems of a diagnosis of COPD, it should not be based on a single spirometry test. PMID- 27684730 TI - Labile plasma iron, more practical and more sensitive to iron overload in myelodysplastic syndromes. AB - OBJECTIVES: In order to gain an insight into labile plasma iron (LPI) in iron metabolism microenvironment in MDS. METHODS: We performed ELISA, quantitative real-time polymerase chain reaction, flow cytometry, MRI T2* assays to test LPI, iron biochemical parameters, and liver iron concentration (LIC) among 22 MDS patients. RESULTS: LPI has a statistical difference (P < 0.001 by analysis of variance (ANOVA)), which decreased gradually, among three groups, while no difference was found in adjusted serum ferritin (ASF) (P = 0.086 by ANOVA). After DFO treatment, serum hepcidin expression increased from 301.26 +/- 59.78 to 340.33 +/- 49.78 ug/l (P = 0.032), while hepcidin/ASF was upregulated gradually from 0.16 +/- 0.08 to 0.22 +/- 0.03 (P = 0.045). APAF-1 expression (P = 0.047) and erythroid apoptosis rate (P = 0.009) decreased significantly, respectively. No statistical difference was found in EPO (P = 0.247) and GDF15 expression (P = 0.172). LIC dropped from 9.83 +/- 4.84 to 6.28 +/- 4.01 mg/g dry weight (P < 0.001). No significant difference was found in cardiac T2* (P = 0.594). LPI has a closer connection to LIC than ASF (r = 0.739, P < 0.001 vs. r = 0.321, P = 0.034). DISCUSSION: LPI seems to be a real-time indicator which reflects body iron loading status instantaneously. Despite the limited knowledge available on LPI speciation in different types and degrees of IO, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens. PMID- 27684729 TI - Recording Gamma Band Oscillations in Pedunculopontine Nucleus Neurons. AB - Synaptic efferents from the PPN are known to modulate the neuronal activity of several intralaminar thalamic regions (e.g., the centrolateral/parafascicular; Cl/Pf nucleus). The activation of either the PPN or Cl/Pf nuclei in vivo has been described to induce the arousal of the animal and an increment in gamma band activity in the cortical electroencephalogram (EEG). The cellular mechanisms for the generation of gamma band oscillations in Reticular Activating System (RAS) neurons are the same as those found to generate gamma band oscillations in other brains nuclei. During current-clamp recordings of PPN neurons (from parasagittal slices from 9 - 25 day-old rats), the use of depolarizing square steps rapidly activated voltage-dependent potassium channels that prevented PPN neurons from being depolarized beyond -25 mV. Injecting 1 - 2 sec long depolarizing current ramps gradually depolarized PPN membrane potential resting values towards 0 mV. However, injecting depolarizing square pulses generated gamma-band oscillations of membrane potential that showed to be smaller in amplitude compared to the oscillations generated by ramps. All experiments were performed in the presence of voltage-gated sodium channels and fast synaptic receptors blockers. It has been shown that the activation of high-threshold voltage-dependent calcium channels underlie gamma-band oscillatory activity in PPN neurons. Specific methodological and pharmacological interventions are described here, providing the necessary tools to induce and sustain PPN subthreshold gamma band oscillation in vitro. PMID- 27684731 TI - GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact. AB - To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL. PMID- 27684732 TI - Why do captive pied tamarins give birth during the day? AB - Diurnal primates typically give birth at night, when it is presumed that they are safer at a very vulnerable time, and this is reflected in an overwhelmingly nocturnal pattern of delivery in most species of Callitrichidae. However, over half (51.1%) of 88 births to pied tamarins (Saguinus bicolor) at Durrell Wildlife Park occurred during the day (0800-1700), almost always in the afternoon. Nearly three quarters of breeding females (17/23) had at least one diurnal birth, including females from all generations in captivity from wild-caught to fifth captive-born generation, and from all six matrilines represented at Durrell. The proportion of diurnal births has remained relatively stable over time despite management changes. We used generalized linear mixed modeling to investigate several factors that we hypothesized could affect time of birth: maternal experience, season, female rearing history, and whether or not the group was on public display. We fitted all possible models to the data, but none explained more than 7.5% of the variation. Daytime delivery had few statistically significant detrimental effects, although infant survival was somewhat lower and parental rejection increased in diurnal births. Pied tamarins do not seem to fit any of the hypotheses previously put forward to explain exceptions to the typical primate circadian pattern of delivery. Zoo Biol. 35:487-494, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27684733 TI - Increased serum leptin and visfatin levels in patients with diffuse idiopathic skeletal hyperostosis: a comparative study. PMID- 27684734 TI - Best Practices for Genomic Assay Testing in Early-Stage Breast Cancer: Clinical and Medicolegal Perspectives. PMID- 27684736 TI - Analyse qualitative data. PMID- 27684735 TI - Integrated High-Performance Infrared Phototransistor Arrays Composed of Nonlayered PbS-MoS2 Heterostructures with Edge Contacts. AB - Molybdenum disulfide (MoS2) has attracted a great deal of attention in optoelectronic applications due to its high mobility, low off-state current and high on/off ratio. However, its intrinsic large bandgap limits its application in infrared detection. Here, we have developed a high-performance infrared photodetector by integrating nonlayered PbS and layered MoS2 nanostructures via van der Waals epitaxy. Density functional theory (DFT) calculations indicate that PbS nanoplates are in contact with MoS2 edges through strong chemical hybridization, which is expected to offer a fast transmission path for carriers that enhances the response speed. The phototransistor exhibits a fast response (taurising = taudecay = 7.8 ms) as well as high photoresponsivity (4.5 * 104 A.W 1) and Ilight/Idark (1.3 * 102) in the near-infrared spectral region at room temperature. In particular, the detectivity (D*) is as high as 3 * 1013 Jones, which is even better than that of commercial Si and InGaAs photodetectors. Furthermore, by controlling the growth and microfabrication patterning, periodic device arrays of PbS-MoS2 that are capable of infrared detection are achieved on Si/SiO2 substrates. Our work provides a possible method for the integration of photodetector arrays on Si-based electronic devices and lays a solid foundation for the practical applications of MoS2-based devices in the future. PMID- 27684737 TI - "Restorative Leadership" in the Digital Era of Implantology. PMID- 27684739 TI - Suppression of abnormal morphology and extracytoplasmic function sigma activity in Bacillus subtilis ugtP mutant cells by expression of heterologous glucolipid synthases from Acholeplasma laidlawii. AB - Glucolipids in Bacillus subtilis are synthesized by UgtP processively transferring glucose from UDP-glucose to diacylglycerol. Here we conclude that the abnormal morphology of a ugtP mutant is caused by lack of glucolipids, since the same morphology arises after abolition of glucolipid production by disruption of pgcA and gtaB, which are involved in UDP-glucose synthesis. Conversely, expression of a monoglucosyldiacylglycerol (MGlcDG) produced by 1,2 diacylglycerol 3-glucosyltransferase from Acholeplasma laidlawii (alMGS) almost completely suppressed the ugtP disruptant phenotype. Activation of extracytoplasmic function (ECF) sigmas (SigM, SigV, and SigX) in the ugtP mutant was decreased by alMGS expression, and was suppressed to low levels by MgSO4 addition. When alMGS and alDGS (A. laidlawii 1,2-diacylglycerol-3-glucose (1-2) glucosyltransferase producing diglucosyldiacylglycerol (DGlcDG)) were simultaneously expressed, SigX activation was repressed to wild type level. These observations suggest that MGlcDG molecules are required for maintenance of B. subtilis cell shape and regulation of ECF sigmas, and DGlcDG regulates SigX activity. PMID- 27684738 TI - Soil Lysimeter Excavation for Coupled Hydrological, Geochemical, and Microbiological Investigations. AB - Studying co-evolution of hydrological and biogeochemical processes in the subsurface of natural landscapes can enhance the understanding of coupled Earth system processes. Such knowledge is imperative in improving predictions of hydro biogeochemical cycles, especially under climate change scenarios. We present an experimental method, designed to capture sub-surface heterogeneity of an initially homogeneous soil system. This method is based on destructive sampling of a soil lysimeter designed to simulate a small-scale hillslope. A weighing lysimeter of one cubic meter capacity was divided into sections (voxels) and was excavated layer-by-layer, with sub samples being collected from each voxel. The excavation procedure was aimed at detecting the incipient heterogeneity of the system by focusing on the spatial assessment of hydrological, geochemical, and microbiological properties of the soil. Representative results of a few physicochemical variables tested show the development of heterogeneity. Additional work to test interactions between hydrological, geochemical, and microbiological signatures is planned to interpret the observed patterns. Our study also demonstrates the possibility of carrying out similar excavations in order to observe and quantify different aspects of soil-development under varying environmental conditions and scale. PMID- 27684741 TI - Searching new targets to counter drug resistance - GTPase-Obg mRNA expression analysis in Mycobacterium under stress and in silico docking with GTPase inhibitors. PMID- 27684740 TI - Effects of an extended flexible regimen of an oral contraceptive pill containing 20 MUg ethinylestradiol and 3 mg drospirenone on menstrual-related symptoms: a randomised controlled trial. AB - OBJECTIVES: The aim of the study was to assess the efficacy for menstrual-related symptoms of an extended flexible regimen of an oral contraceptive pill containing 20 MUg ethinylestradiol and 3 mg drospirenone in comparison with a 24/4 d cyclical regimen of the same formulation. METHODS: This randomised, non inferiority, open-label, multicentre study was conducted in women aged 18-39 years. Their menstrual-related symptoms were assessed using the Penn Daily Symptom Rating (DSR17). Participants were randomised to use an extended flexible regimen of 20 MUg ethinylestradiol and 3 mg drospirenone (EE/DRSPe.flex), comprising 168 consecutive days with a 4-d hormone-free interval (HFI, allowing for management of unexpected bleeding) or a conventional 24/4 cyclical regimen of the same pill (EE/DRSP24/4). The primary measure of efficacy was the percentage change in DSR17 total score from baseline to cycle 6. The secondary measures of efficacy were the percentage changes in DSR17 total score from baseline after each 28-d interval throughout the entire study and in the scores for individual DSR17 symptoms. RESULTS: The primary analysis demonstrated that EE/DRSPe.flex was not inferior to EE/DRSP24/4 (Mean DSR17 score 9.1; 95% confidence interval (CI) - 2.5, 20.6; p = 0.123). Analysis at intervals throughout the entire evaluation period showed greater reduction in DSR17 total score for EE/DRSPe.flex than for the 24/4 regimen (p < 0.001). The decreases in individual scores for the symptoms 'poor coordination' and 'depression/feeling sad/down or blue' were greater for the extended flexible regimen than for the cyclical regimen (p < 0.05). CONCLUSION: The extended flexible regimen was not inferior to the 24/4 cyclical regimen in terms of the primary endpoint. It significantly improved symptoms in the interval analysis, and the effects on specific DSR17 symptoms, compared with the cyclical regimen. PMID- 27684742 TI - Production of Materials with Spatially-Controlled Cross-Link Density via Vat Photopolymerization. AB - We describe an efficient method to produce objects comprising spatially controlled and graded cross-link densities using vat photopolymerization additive manufacturing (AM). Using a commercially available diacrylate-based photoresin, 3D printer, and digital light processing (DLP) projector, we projected grayscale images to print objects in which the varied light intensity was correlated to controlled cross-link densities and associated mechanical properties. Cylinder and bar test specimens were used to establish correlations between light intensities used for printing and cross-link density in the resulting specimens. Mechanical testing of octet truss unit cells in which the properties of the crossbars and vertices were independently modified revealed unique mechanical responses from the different compositions. From the various test geometries, we measured changes in mechanical properties such as increased strain-to-break in inhomogeneous structures in comparison with homogeneous variants. PMID- 27684743 TI - Proceedings of the Canadian Society for Exercise Physiology Annual General Meeting - From Health to High Performance / Compte rendu du congres annuel de la Societe canadienne de physiologie de l'exercice - " From Health to High Performance ". PMID- 27684744 TI - Assaying Predatory Feeding Behaviors in Pristionchus and Other Nematodes. AB - This protocol provides multiple methods for the analysis and quantification of predatory feeding behaviors in nematodes. Many nematode species including Pristionchus pacificus display complex behaviors, the most striking of which is the predation of other nematode larvae. However, as these behaviors are absent in the model organism Caenorhabditis elegans, they have thus far only recently been described in detail along with the development of reliable behavioral assays (1). These predatory behaviors are dependent upon phenotypically plastic but fixed mouth morphs making the correct identification and categorization of these animals essential. In P. pacificus there are two mouth types, the stenostomatous and eurystomatous morphs (2), with only the wide mouthed eurystomatous containing an extra tooth and being capable of killing other nematode larvae. Through the isolation of an abundance of size matched prey larvae and subsequent exposure to predatory nematodes, assays including both "corpse assays" and "bite assays" on correctly identified mouth morph nematodes are possible. These assays provide a means to rapidly quantify predation success rates and provide a detailed behavioral analysis of individual nematodes engaged in predatory feeding activities. In addition, with the use of a high-speed camera, visualization of changes in pharyngeal activity including tooth and pumping dynamics are also possible. PMID- 27684745 TI - Differing Causes of Lactic Acidosis and Deep Breathing in Cerebral Malaria and Severe Malarial Anemia May Explain Differences in Acidosis-Related Mortality. AB - Lactic acidosis (LA) is a marker for mortality in severe malaria, but the mechanisms that lead to LA in the different types of severe malaria and the extent to which LA-associated mortality differs by type of severe malaria are not well described. We assessed the frequency of LA in children admitted to Mulago Hospital, Kampala, Uganda with cerebral malaria (CM, n = 193) or severe malarial anemia (SMA, n = 216). LA was compared to mortality and measures of parasite biomass and sequestration (P. falciparum histidine-rich protein-2 (PfHRP2) concentration, platelet count), and to a measure of systemic tissue oxygen delivery (hemoglobin level). LA was more frequent in children with SMA than CM (SMA, 47.7%, CM, 34.2%, P = 0.006), but mortality was higher in children with CM (13.0%) than SMA (0.5%, P<0.0001). In CM, LA was associated with increased PfHRP2 concentration and decreased platelet count but was not associated with hemoglobin level. In contrast, in SMA, LA was associated with a decreased hemoglobin level, but was not associated with PfHRP2 concentration or platelet count. LA was related to mortality only in CM. In multivariable regression analysis of the effect PfHRP2 and hemoglobin levels on LA and DB, only PfHRP2 level increased risk of LA and DB in CM, while in SMA, elevated hemoglobin strongly decreased risk of LA and DB, and PfHRP2 level modestly increased risk of LA. The study findings suggest that LA in CM is due primarily to parasite sequestration, which currently has no effective adjunctive therapy, while LA in SMA is due primarily to anemia, which is rapidly corrected with blood transfusion. Differing etiologies of LA in CM and SMA may explain why LA is associated with mortality in CM but not SMA. PMID- 27684746 TI - Transplantation Into the Mouse Ovarian Fat Pad. AB - Orthotopic transplantation assays in mice are invaluable for studies of cell regeneration and neoplastic transformation. Common approaches for orthotopic transplantation of ovarian surface and tubal epithelia include intraperitoneal and intrabursal administration of cells. The respective limitations of these methods include poorly defined location of injected cells and limited space volume. Furthermore, they are poorly suited for long-term structural preservation of transplanted organs. To address these challenges, we have developed an alternative approach, which is based on the introduction of cells and tissue fragments into the mouse fat pad. The mouse ovarian fat pad is located in the immediate vicinity of the ovary and uterine tube (aka oviduct, fallopian tube), and provides a familiar microenvironment for cells and tissues of these organs. In our approach fluorescence-labeled mouse and human cells, and fragments of the uterine tube are engrafted by using minimally traumatic dorsal incision surgery. Transplanted cells and their outgrowths are easily located in the ovarian fat pad for over 40 days. Long-term transplantation of the entire uterine tube allows correct preservation of all principle tissue components, and does not result in adverse side effects, such as fibrosis and inflammation. Our approach should be uniquely applicable for answering important biological questions such as differentiation, regenerative and neoplastic potential of specific cell populations. Furthermore, it should be suitable for studies of microenvironmental factors in normal development and cancer. PMID- 27684747 TI - High-throughput Screening of Carbohydrate-degrading Enzymes Using Novel Insoluble Chromogenic Substrate Assay Kits. AB - Carbohydrates active enzymes (CAZymes) have multiple roles in vivo and are widely used for industrial processing in the biofuel, textile, detergent, paper and food industries. A deeper understanding of CAZymes is important from both fundamental biology and industrial standpoints. Vast numbers of CAZymes exist in nature (especially in microorganisms) and hundreds of thousands have been cataloged and described in the carbohydrate active enzyme database (CAZy). However, the rate of discovery of putative enzymes has outstripped our ability to biochemically characterize their activities. One reason for this is that advances in genome and transcriptome sequencing, together with associated bioinformatics tools allow for rapid identification of candidate CAZymes, but technology for determining an enzyme's biochemical characteristics has advanced more slowly. To address this technology gap, a novel high-throughput assay kit based on insoluble chromogenic substrates is described here. Two distinct substrate types were produced: Chromogenic Polymer Hydrogel (CPH) substrates (made from purified polysaccharides and proteins) and Insoluble Chromogenic Biomass (ICB) substrates (made from complex biomass materials). Both CPH and ICB substrates are provided in a 96-well high-throughput assay system. The CPH substrates can be made in four different colors, enabling them to be mixed together and thus increasing assay throughput. The protocol describes a 96-well plate assay and illustrates how this assay can be used for screening the activities of enzymes, enzyme cocktails, and broths. PMID- 27684748 TI - Choosing a President. AB - This campaign season has set new bars-both high and low. PMID- 27684749 TI - Should Health Care Providers Support Electronic Cigarettes for Smoking Cessation? AB - Evidence on safety and effectiveness isn't yet conclusive. PMID- 27684750 TI - Mentoring New Nurses. PMID- 27684751 TI - Palliative Nursing. PMID- 27684752 TI - The Demise of Consented Autopsy. PMID- 27684753 TI - Improving Safety in Older Drivers. AB - Nurses can educate families and help assess older adults at risk for unsafe driving. PMID- 27684755 TI - Five Variables Predict Whether Newly Licensed Nurses Stay on a Unit or Transfer. AB - Variety and autonomy top a list that includes job satisfaction and a BSN or higher degree. PMID- 27684758 TI - Britain Honors Mary Seacole with a Memorial. AB - Is the statue stealing the spotlight from the Lady with a Lamp? Some say yes. PMID- 27684759 TI - Analysis Finds About 20 Veterans Died Daily from Suicide Between 2001 and 2014. AB - The VA is launching aggressive measures aimed at prevention. PMID- 27684761 TI - Little Evidence for Routine Visual Screening for Skin Cancer, Says the USPSTF. AB - The statement refers only to asymptomatic adults with no history of skin cancer. PMID- 27684762 TI - Helping Elders 'Age in Place'. AB - With community commitment, older adults can remain healthy, independent, and in their own homes. PMID- 27684765 TI - Nursing, Health Care, and the 2016 Presidential Race. AB - Nurses, whatever their political leanings, can influence the public conversation on health care. PMID- 27684766 TI - Stronger Warning for Two Diabetes Drugs. PMID- 27684767 TI - Loperamide Abuse or Misuse Triggers Cardiac Events. PMID- 27684772 TI - For Advanced Cancer, What Treatment Is Next? AB - This article is the second in a series on palliative care developed in collaboration with the Hospice and Palliative Nurses Association (HPNA; http://hpna.advancingexpertcare.org). The HPNA aims to guide nurses in preventing and relieving suffering and in giving the best possible care to patients and families, regardless of the stage of disease or the need for other therapies. The HPNA offers education, certification, advocacy, leadership, and research. PMID- 27684768 TI - New Drug Treats All Genotypes of Chronic HCV. PMID- 27684773 TI - Seeing Potential: The Joys of Teaching Nursing. AB - Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely-and often more personal perspectives on professional, policy, and clinical issues. Best of the Blog will be a regular column to bring AJN readers recent posts that we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com. PMID- 27684774 TI - Determining When an Activity Is or Is Not Research. AB - Practical and ethical considerations for nurses engaged in QI and other projects. PMID- 27684775 TI - Nurse-Led Intervention Helps Improve Infant Sleep. PMID- 27684776 TI - Acupressure Reduces Breast Cancer-Related Fatigue. PMID- 27684777 TI - Undiagnosed Valvular Heart Disease is Common in Older Adults. PMID- 27684778 TI - Rotating Night-Shift Work is Associated With Increased CHD Risk in Female RNS. PMID- 27684779 TI - Adjuvant Corticosteroid Therapy for Acute Bacterial Meningitis. AB - Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. PMID- 27684780 TI - Teaching Children to Be Health Educators. AB - : A nursing school, an elementary school, and several local organizations initiated a pilot project to address hypertension in rural Hawaii. Their goal was to help increase awareness of hypertension in the community by partnering with sixth-grade students as health educators. As part of their pediatric clinical rotation, nursing students developed a curriculum and taught the elementary school students to take and record blood pressures. The sixth graders learned to use blood pressure monitors and took and recorded over 1,500 of their friends' and family members' blood pressures. The students were also able to correctly identify elevated findings. This pilot project is an example of how children can be taught to participate in a community collaboration to promote health care in their community. PMID- 27684781 TI - Speaking Up to Save a Life. AB - A nurse's advocacy alters the path of a patient with locked-in syndrome. PMID- 27684782 TI - The Traumatized Patient. AB - An irredeemable pain lies beneath some patients' nonspecific symptoms. PMID- 27684783 TI - Lack of virological and serological evidence for continued circulation of highly pathogenic avian influenza H5N8 virus in wild birds in the Netherlands, 14 November 2014 to 31 January 2016. AB - In 2014, H5N8 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage emerged in poultry and wild birds in Asia, Europe and North America. Here, wild birds were extensively investigated in the Netherlands for HPAI H5N8 virus (real-time polymerase chain reaction targeting the matrix and H5 gene) and antibody detection (haemagglutination inhibition and virus neutralisation assays) before, during and after the first virus detection in Europe in late 2014. Between 21 February 2015 and 31 January 2016, 7,337 bird samples were tested for the virus. One HPAI H5N8 virus-infected Eurasian wigeon (Anas penelope) sampled on 25 February 2015 was detected. Serological assays were performed on 1,443 samples, including 149 collected between 2007 and 2013, 945 between 14 November 2014 and 13 May 2015, and 349 between 1 September and 31 December 2015. Antibodies specific for HPAI H5 clade 2.3.4.4 were absent in wild bird sera obtained before 2014 and present in sera collected during and after the HPAI H5N8 emergence in Europe, with antibody incidence declining after the 2014/15 winter. Our results indicate that the HPAI H5N8 virus has not continued to circulate extensively in wild bird populations since the 2014/15 winter and that independent maintenance of the virus in these populations appears unlikely. PMID- 27684784 TI - Tetracycline absorbed onto nitrilotriacetic acid-functionalized magnetic graphene oxide: Influencing factors and uptake mechanism. AB - A novel magnetic nanomaterial was synthesized by grafting nitrilotriacetic acid to magnetic graphene oxide (NDMGO), which was applied as an adsorbent for removing tetracycline (TC) from aqueous solutions. The nanomaterial was characterized using TG-DTA, SEM, TEM, XRD, VSM, XPS, Raman, BET surface area and zeta potential measurements. Several experimental conditions (solution pH, adsorption time, temperature, ionic strength and foreign ions) affecting the adsorption process were investigated. The results showed that the TC adsorption capacity could be affected by solution pH. The adsorption capacity of TC increased rapidly in the initial 20min and finally reached equilibrium was about 600min. The pseudo-second-order kinetics provided the better correlation for the experiment data. Various thermodynamic parameters indicated that the adsorption was a spontaneous and endothermic process. The presence of NaCl and background electrolytes in the solution had a slight influence on TC adsorption. Hydrogen bonds, amidation reaction, pi-pi and cation-pi interaction between NDMGO and TC could be used to explain the adsorption mechanism. The regeneration experiment demonstrated that this nanomaterial possessed an excellent regeneration performance. Based on the experimental results and comparative analysis with other adsorbents, the NDMGO was a high-efficiency and reusable adsorbent for TC pollution control. PMID- 27684785 TI - A polyoxometalate-based supramolecular chemosensor for rapid detection of hydrogen sulfide with dual signals. AB - Hydrogen sulfide (H2S) has been verified as an important biological mediator in human physiological activities, but its rapid and accurate detection is remaining a challenge. Based on our early work, Eu-containing polyoxometalate/ionic liquid type gemini surfactant hybrid nanoparticles fabricated by EuW10O36.32H2O (Eu-POM) and 1,2-bis(3-hexadecylimidazolium-1-yl) ethane bromide ([C16-2-C16im]Br2) via ionic self-assembly (ISA) strategy, we modified the hybrids with copper (II) ion and used them as a novel turn-off supramolecular fluorescence probe for H2S immediate response. Although copper (II) ions can cause decrease of the fluorescence intensity, the probe with moderate amount of copper (II) still has a high performance in emission property. The copper (II) ion-modified supramolecular sensor (CSS) shows dual signals in the fluorescence intensity and absorbance for H2S detection, and the detection limit is about1.25MUM. Furthermore, CSS displays high selectivity for H2S in the presence of other anions and species (e.g. Cl-, Br-, I-, SO42-, SO32-, S2O32-, AC-, H2O2, HCO3-, l cysteine, homocysteine and l-glutathione), and also have potential for preferential imaging in vivo. Besides, the fluorescence quenching mechanism of CSS in the presence of H2S was explored. CuS generated by the reaction between Cu2+ and H2S was testified to act as a quencher, and the nonradiative resonance energy transfer mechanism was speculated to be responsible for fluorescence quenching. It is anticipated that the as-prepared CSS will be used as an efficient chemosensor for the rapid detection of H2S, which is critical for the diagnosis of some diseases, e.g. Alzhermer's disease, Down's syndrome, and diabetes, etc. PMID- 27684786 TI - Poly-l-lysine/heparin multilayer coatings prevent blood protein adsorption. AB - The adsorption of blood proteins, serum albumin (BSA), immunoglobulin G (IgG) and fibrinogen (FGN), onto model SiO2 planar surfaces coated with poly-l lysine/heparin multilayers (PLL/HEP) has been investigated by means of ellipsometry and quartz crystal microbalance with dissipation. Aiming at the development of low fouling coatings, this study has been focused on the effects that the number of layers and the type of polyelectrolyte present on the topmost layer have on the adsorption of these proteins. The three proteins interact with PLL-ended coatings whereas HEP-ended coatings prevent the adsorption of both BSA and IgG and induce a decrease in the adsorbed amount of FGN, down to 0.4mg/m2 for three bilayers, as the number of PLL/HEP bilayers increases. These results suggest that heparin-ended multilayers prevent protein adsorption, which is an indicative of good blood compatibility. As a consequence we propose that PLL/HEP coatings could be used for the development of vascular medical devices. PMID- 27684787 TI - Synthesis and characterization of plasmonic and magnetically separable Ag/AgCl Bi2WO6@ Fe3O4@SiO2 core-shell composites for visible light-induced water detoxification. AB - A magnetic photocatalyst composite (Ag/AgCl-Bi2WO6) was proposed and investigated. Magnetic Bi2WO6 was hydrothermally loaded onto silica-coated Fe3O4 which was synthesized by coprecipitation in addition to a modified Stober process. Ag nanoparticles were then photoreduced on the surface of Bi2WO6. The prepared samples were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible light diffuse reflectance spectroscopy. Magnetic properties were investigated using a superconducting quantum interface magnetometer, with samples exhibiting quasi-superparamagnetic behaviour. The visible light-induced photocatalytic activities were evaluated by degrading a model dye, RhB, as well as a colourless aromatic organic compound, phenol. Samples found to possess an excellent performance in terms of detoxification. Pathways and mechanisms for the photocatalytic degradation of organic compounds in the presence of Ag/AgCl-(M) Bi2WO6 were also investigated and proposed. PMID- 27684788 TI - Averaging of nuclear modulation artefacts in RIDME experiments. AB - The presence of artefacts due to Electron Spin Echo Envelope Modulation (ESEEM) complicates the analysis of dipolar evolution data in Relaxation Induced Dipolar Modulation Enhancement (RIDME) experiments. Here we demonstrate that averaging over the two delay times in the refocused RIDME experiment allows for nearly quantitative removal of the ESEEM artefacts, resulting in potentially much better performance than the so far used methods. The analytical equations are presented and analyzed for the case of electron and nuclear spins S=1/2,I=1/2. The presented analysis is also relevant for Double Electron Electron Resonance (DEER) and Chirp-Induced Dipolar Modulation Enhancement (CIDME) techniques. The applicability of the ESEEM averaging approach is demonstrated on a Gd(III) Gd(III) rigid ruler compound in deuterated frozen solution at Q band (35GHz). PMID- 27684789 TI - Bioactive Sesquiterpenes from the Edible Mushroom Flammulina velutipes and Their Biosynthetic Pathway Confirmed by Genome Analysis and Chemical Evidence. AB - Twelve putative sesquiterpene synthases genes were found in clades along with enzymes with 1,6-, 1,10-, and 1,11-cyclase activities in the genome of Flammulina velutipes. Chemistry investigation of F. velutipes led to the identification of two seco-cuparane sesquiterpenes, flammufuranone A (1) and B (2); 13 new sesquiterpenes with nor-eudesmane, spiroaxane, cadinane, and cuparane skeletons (3-14, 16); as well as two new ergosterol derivatives (17 and 18). Sesquiterpenes (3-14) derived from 1,10-cyclizing enzyme were first reported from this mushroom. The absolute configurations in 1 (3R,7S) and 2 (3R,7R) were assigned by electronic circular dichroism (ECD) calculation. The absolute configuration in 3 was confirmed by X-ray diffraction analysis. The absolute configurations in the 1,2-diol moiety of 13, and in the 1,3-diol moiety of 17 and 18 were determined using Snatzke's method. Among these compounds, 3, 5, 13, and 14 were found to inhibit the HMG-CoA reductase with IC50 of 114.7, 77.6, 55.5, and 87.1 MUM, respectively. Compounds 5, 6, 7, 10, 13, and 14 showed DPP-4 inhibitory activity with IC50 of 75.9, 83.7, 70.9, 79.7, 80.5, and 74.8 MUM, respectively. The biosynthesis for sesquiterpenes in F. velutipes was also discussed. PMID- 27684790 TI - Examining the interplay between depression, motivation, and antiretroviral therapy adherence: a social cognitive approach. AB - A large body of research identifies depressive symptoms as a barrier to optimal antiretroviral therapy (ART) adherence, whereas treatment motivation has been characterized as a facilitator. There is evidence, however, that these patterns may not hold for some ART patients despite the widespread use of motivational techniques aimed at promoting adherence. Little is known about how the interplay between different levels of depressive symptoms and variations in the types and levels of motivation may influence ART adherence. The purpose of this study was to examine the relationship between depressive symptoms, two types of motivation, and adherence, with self-efficacy as a mediator. The sample consisted of 121 ART patients who reported various levels of depressive symptoms (mean age = 41 years; 84% African-American; and 68% female). Path analysis revealed that self-efficacy fully mediated the relationship between the three predictor variables (depressive symptoms, intrinsic motivation, and extrinsic motivation) and adherence, chi2(3, N = 121) = .78, RMSEA = .00, SRMR = .02, CFI = 1.00, NNFI = 1.06. Findings suggest that interventions using motivational techniques to build adherence among patients with varying levels of depressive symptoms should address the role of treatment self-efficacy to improve their effectiveness. PMID- 27684791 TI - Comparison of vitrification and conventional slow freezing for cryopreservation of ovarian tissue with respect to the number of intact primordial follicles: A meta-analysis. AB - BACKGROUND: Vitrification is the standard method for cryopreserving human oocytes and embryos, but its effects on ovarian tissue are uncertain. The purpose of this meta-analysis was to compare the proportion of intact primordial follicles in ovarian tissue cryopreserved with vitrification versus slow freezing. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until November 11, 2014 using combinations of the search terms: ovarian tissue, cryopreservation, vitrification, follicle, follicles. Inclusion criteria were randomized controlled trails, two-arm prospective studies, and retrospective studies in which ovarian tissues were preserved by vitrification or conventional slow freezing. The primary outcome was the proportion of intact primordial follicles. RESULTS: Six studies were included in the meta-analysis. The number of patients ranged from 3 to 20, and age ranged from 20 to 43 years. Total number of morphologically intact follicles ranged from 14 to 2058, among which 6 to 724 were primordial. The pooled odds ratio (OR) showed no significant difference in the proportion of intact primordial follicles after slow freezing or vitrification (OR = 1.228, 95% confidence interval [CI]: 0.769-1.961, P = 0.390). Sensitivity analysis using the leave-one-out approach indicated no considerable changes in the direction and magnitude of the pooled estimates when individual studies were excluded one at a time, indicating good reliability of the current analysis. CONCLUSIONS: Vitrification and slow freezing produce equivalent results with respect to intact primordial follicles for the cryopreservation of human ovarian tissue. However, the included studies varied in the cryopreservation protocols used. PMID- 27684792 TI - Halitosis and helicobacter pylori infection: A meta-analysis. AB - BACKGROUND: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to define the correlation between H pylori infection and halitosis. OBJECTIVES: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication therapy will help relieve halitosis. METHODS: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Screening of titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done using Review Manager 5.2 software. RESULTS: A total of 115 articles were identified, 21 of which met the inclusion criteria and presented data that could be used in the analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis negative patients was 4.03 (95% CI: 1.41-11.50; P = 0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative patients was 2.85 (95% CI: 1.40-5.83; P = 0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected halitosis-positive patients was 0.17 (95% CI: 0.08-0.39; P <0.0001), compared with those patients without successful H pylori eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45-15.80; P = 0.01), compared with after successful H pylori eradication therapy. CONCLUSIONS: There is clear evidence that H pylori infection correlates with halitosis. H pylori infection might be important in the pathophysiological mechanism of halitosis, and H pylori eradication therapy may be helpful in those patients with refractory halitosis. PMID- 27684793 TI - Association of genetic variants in the receptor for advanced glycation end products gene with diabetic retinopathy: A meta-analysis. AB - BACKGROUND: Diabetic retinopathy (DR) is a major sight-threatening diabetic complication. Previous studies have examined the association of DR with multiple genetic variants in the receptor for advanced glycation end products (RAGE) gene, with inconsistent results. OBJECTIVE: To perform a systematic literature search and conduct meta-analyses to examine the association of genetic variants in RAGE with DR. DATA SOURCES: PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Studies were on human subjects; the studies were case-control ones and included subjects who had DR and those who did not have DR; and the studies provided genotype data for genetic variants in RAGE, separately for subjects who had and did not have DR, or provided odds ratios (ORs) and the 95% confidence intervals (CIs), or provided sufficient data for the calculation of OR and the 95% CI. STUDY APPRAISAL AND SYNTHESIS METHODS: We used OR as a measure of association, and used random effects model in all the meta-analyses. Between-study heterogeneity was assessed using I, and publication bias was evaluated using Egger test. RESULTS: A total of 13 studies met the eligibility criteria and were included in our analyses. We found that Gly82Ser was significantly associated with DR (OR = 2.40, 95% CI: 1.46 3.97; P = 0.001) using a recessive model. -374T/A also showed significant association with DR under a dominant model (OR = 1.21, 95% CI: 1.03-1.43; P = 0.023). We did not find a significant association of DR with other genetic variants in RAGE. LIMITATIONS: The number of included studies is small for some genetic variants; duration of diabetes varied across studies; most studies were conducted in Asia; and it is not clear whether the observed association can be generalized to other ethnicities; and we could not control for other potential confounding factors. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: We found that Gly82Ser in RAGE showed significant association with DR. More studies with larger sample sizes that control for important risk factors, such as duration of diabetes, are needed to validate our findings. PMID- 27684794 TI - Lack of increased signal intensity in the dentate nucleus after repeated administration of a macrocyclic contrast agent in multiple sclerosis: An observational study. AB - Recently, several studies reported increased signal intensity (SI) in the dentate nucleus (DN) after repeated application of gadolinium-based contrast agents (GBCAs), suggesting a deposition of gadolinium in this location. Patients with relapsing-remitting multiple sclerosis (RRMS) frequently show increased permeability of the blood-brain barrier as part of the inflammatory process in the brain parenchyma, which theoretically might increase the risk of gadolinium deposition. In this retrospective study, we investigated a possible increasing SI in the DN after repeated administrations of the macrocyclic contrast agent gadoterate meglumine.Forty-one RRMS patients (33 women, mean age 38 years) with at least 6 prior gadolinium-enhanced examinations (single dose gadoterate meglumine) were identified. A total of 279 unenhanced T1-weighted examinations were analyzed.SI ratio differences did not differ between the first and last MRI examination, neither for the DN-to-pons ratio (P = 0.594) nor for the DN-to cerebellum ratio (P = 0.847). There was no correlation between the mean DN-to pons, or between the mean DN-to-cerebellum SI ratio and the number of MRI examinations (P = 0.848 and 0.891), disease duration (P = 0.676 and 0.985), and expanded disability status scale (EDSS) (P = 0.639 and 0.945).We found no signal increases in the DN after a minimum of 6 injections of the macrocyclic GBCA gadoterate meglumine in RRMS patients. This warrants further investigations in regard to the true pathophysiologic basis of intracerebral gadolinium deposition. PMID- 27684795 TI - Risk assessment of obstructive sleep apnea syndrome in pediatric patients with vitamin D deficiency: A questionnaire-based study. AB - The aim of the following study is to evaluate the risk of obstructive sleep apnea syndrome (OSAS) in subjects with vitamin D deficiency.Prospective and comparative study.We enrolled 240 subjects into the study. The participants were divided into 2 groups based on 25-hydroxyvitamin D (25[OH]D) levels: low level of 25(OH)D (<20 ng/mL) group (n = 120) and control (>20 ng/mL) group (n = 120). Subjects were classified as being at a high or low risk of developing OSAS by using the Berlin Questionnaire. Risk of developing OSAS, gender, age, and body mass index (BMI) z score were assessed by comparing the low level of 25(OH)D group and control group.No statistically significant difference was observed between the low level of 25(OH)D group and control group in terms of gender, age, and BMI z-score distributions; P = 0.323, P = 0.387, and P = 0.093, respectively. There were 24 subjects with high risk of developing OSAS in 2 groups (17 subjects in the low level of 25[OH]D group and 7 subjects in the control group). In the low level of 25(OH)D group, the risk of developing OSAS was found to be significantly higher than the control group (P = 0.030). BMI z-score was found significantly higher in high-risk groups than low-risk groups (P = 0.034 for low-level 25[OH]D group and P = 0.023 for control group).The findings revealed that low level of 25(OH)D increases the risk of developing OSAS. PMID- 27684796 TI - Signal intensity ratio on magnetic resonance imaging as a prognostic factor in patients with cervical compressive myelopathy. AB - Patients with intramedullary signal intensity (SI) changes have a poor prognosis after surgical decompression in cervical compressive myelopathy (CCM); however, some patients show no clear relationship between the SI and postsurgical prognosis. This discrepancy may be because no comprehensive and proper quantitative evaluation exists to assess SI on magnetic resonance imaging (MRI). The purpose of this study was prospectively to evaluate the correlation between the clinical features, neurological outcome of patients with CCM, and the quantitative assessment of SI changes preoperatively and postoperatively, and the correlation with SI severity.A total of 112 patients with CCM at 1 or 2 levels underwent anterior cervical discectomy and fusion. We quantitatively analyzed MR signal changes on T1-weighted MR images (T1WI), gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) contrast-enhanced T1WI, and T2 weighted MR images (T2WI) using the signal intensity ratio (SIR). We evaluated the correlations between various variables and neurological outcome using the Japanese Orthopedic Association (JOA) scale, and the severity of SI change by grade (i.e., grade 0 ["none"], grade 1 ["light"], and grade 2 ["bright on T2WI"]).Significant differences between the 3 grades existed in symptom duration, preoperative JOA score, SIR on T2WI, and JOA recovery ratio. The JOA recovery ratio was negatively correlated with symptom duration and the SIR on T2WI, and positively correlated with the preoperative JOA score and cord compression ratio, but not with the SIR on T1WI and contrast-enhanced T1WI. On the postoperative 12 month follow-up MRI, the JOA recovery ratio and SIR on T2WI of the SI reversal patients were better than those of the nonreversal patients. On multiple regression analysis, the SIR on T2WI was the main significant prognostic factor of surgical outcome.The grading system on T2WI provided reliable predictive information for neurological outcome. Quantitative alterations in the SI on preoperative and postoperative T2WI, but not T1WI or contrast-enhanced T1WI, reflected the clinical features, surgical outcomes, and the correlation with SI severity. The patients with a longer duration of symptoms, lower cord compression ratio, severe myelopathy, intense signal change (i.e., grade 2) on the spinal cord, and an SIR greater than 1.55 had a poor recovery after a surgical operation. PMID- 27684797 TI - The value of 3-dimensional longitudinal strain in the evaluation of complex coronary lesions in non-ST-segment elevation acute coronary syndrome patient. AB - The aim of this study is to investigate the value of 3-dimensional global peak longitudinal strain (GPLS) derived from the 3-dimensional speckle-tracking echocardiography (3D-STE) in the diagnosis of the complex non-ST-segment elevation acute coronary syndromes (NSTE-ACS) by comparing GPLS to the synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score.A total of 59 inpatients with NSTE-ACS in our hospital between October 2014 and January 2015 were enrolled into our study. All these subjects underwent the coronary angiography (CAG) and 3D-STE examination. The results of CAG were used to calculate the SYNTAX scores in each subject. The GPLS was assessed with speckle-tracking analysis using the dedicated software developed by GE Healthcare (Horten, Norway).We grouped all subjects according to the SYNTAX scores. A total of 23 patients (39%) were grouped as complex NSTE-ACS in our experiment. In our analysis, the values of GPLS significantly decreased from low SYNTAX scores to intermediate or high SYNTAX scores (-14.0 +/- 2.7% and -9.5 +/- 2.8%, respectively, P < 0.001). Multivariate regression analysis showed that GPLS and diabetes mellitus were independent predictors for complex NSTE-ACS. The area under the receiver operator characteristic curve (AUC) for GPLS to evaluate patients with complex NSTE-ACS was 0.882 (95% confidence interval [CI], 0.797 0.967, P < 0.001) with an optimal cutoff value of -11.76% (sensitivity 82.6% and specificity 83.3%). The evaluative value of the adjusted AUC for evaluating patients with complex NSTE-ACS improved after inclusion of GPLS (C statistics, 0.827-0.948, P < 0.001).The value of GPLS is significantly associated with the complexity of coronary artery lesions, according to SYNTAX score. Therefore, our study indicates that GPLS could be reproducible and efficient to evaluate the complex coronary artery disease in NSTE-ACS patients. PMID- 27684798 TI - Association of obstructive sleep apnea plus hypertension and prevalent cardiovascular diseases: A cross-sectional study. AB - Current study sought to evaluate the associations of obstructive sleep apnea (OSA) plus hypertension (HTN) and prevalent cardiovascular diseases (CVD).This was a cross-sectional study and a total of 1889 subjects were enrolled. The apnea hypopnea index (AHI) was measured by polysomnography and OSA degree was classified as mild (AHI 5-14.9) and moderate-severe (AHI >= 15), and AHI < 5 was considered no-OSA. Mean and lowest oxyhemoglobin saturation (SaO2) was detected by pulse oximetry. Between-group differences were assessed and logistic regression analysis was used to analyze the association of OSA plus HTN and prevalent CVD.Compared to normotensive subjects, hypertensive subjects were older and had higher body mass index (BMI), neck girth, waist-hip ratio, AHI, and low density lipoprotein cholesterol (LDL-C) level. Conversely, mean and lowest SaO2 levels were significantly lower. Logistic regression analysis showed that in an unadjusted model, compared to subjects with no-OSA and no-HTN (reference group), the association of HTN plus moderate-severe-OSA and prevalent CVD was the most prominent (odds ratio [OR]: 2.638 and 95% confidence interval [CI]: 1.942-3.583). In normotensive subjects, after adjusted for potential covariates, the associations of OSA (regardless of severity) and prevalent CVD were attenuated to nonsignificant. In hypertensive subjects, however, the associations remained significant but were reduced. Further adjusted for mean and lowest SaO2, the associations remained significant in HTN plus no-OSA (OR: 1.808, 95% CI: 1.207 2.707), HTN plus mild-OSA (OR: 2.003, 95% CI: 1.346-2.980), and HTN plus moderate severe OSA (OR: 1.834, 95% CI: 1.214-2.770) groups.OSA plus HTN is associated with prevalent CVD, and OSA may potentiate the adverse cardiovascular effects on hypertensives patients but not normotensives. PMID- 27684799 TI - Cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus: A case report. AB - BACKGROUND: Hypertrophic pachymeningitis (HP) is a chronic disease characterized by inflammatory hypertrophy and fibrosis of dura mater. It can be divided into cranial and spinal forms depending on the location of the lesion. HP involving 2 separate sites simultaneously is quite uncommon. CASE SUMMARY: This study presents a case of a 49-year-old woman with pathologically confirmed cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus (SLE), which is a rare etiology of HP. She experienced persistent numbness and pain of the left lower limb, followed by headache and seizures. In laboratory tests, levels of erythrocyte sedimentation rate and C-reactive protein were elevated, and antinuclear antibodies and anti-double-strand deoxyribonucleic acid (DNA) antibodies were detected. Magnetic resonance imaging revealed dural thickening with homogenous gadolinium enhancement both at lumbosacral level and over cerebral convexities. Histology suggested chronic inflammation in spinal dura mater with extensive fibrosis, dense lymphoplasmacytic infiltrate, and focal vasculitis. Treatment with corticosteroids and cyclophosphamide was started with significant clinical and radiological improvement. CONCLUSION: HP is etiologically heterogeneous. Despite its rarity, SLE should be considered in the differential diagnosis of HP. Early recognition and therapy may provide an optimal outcome. PMID- 27684800 TI - Impact of early life adversity on EMG stress reactivity of the trapezius muscle. AB - Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID- 27684801 TI - Adaptation and validation of an adverse drug reaction preventability score for bleeding due to vitamin K antagonists. AB - Although drug therapy is inherently associated with the risk of adverse drug reactions (ADRs), some of these events are preventable. The estimated proportion of preventable ADRs varies from one study or clinical context to another. Bleeding caused by antithrombotic agents (and particularly vitamin K antagonists, VKAs) constitutes one of the most frequent causes of ADR-related hospitalization.Hence, the objective of the present study was to adapt and validate an ADR preventability score for bleeding due to VKAs and evaluate the preventability of bleeding in 906 consecutive hospitalized, VKA-treated adult patients with a risk of major bleeding (defined as an international normalized ratio >=5) over a 2-year period. A specific preventability scale for VKA associated bleeding was developed by adapting a published tool.Overall, 241 of the 906 patients in the study experienced at least 1 VKA-associated bleeding event. The scale's reliability was tested by 2 different evaluators. The inter rater reliability (evaluated by calculation of Cohen's kappa) ranged from "good" to "excellent." Lastly, the validated scale was used to assess the preventability of the VKA-associated bleeding. We estimated that bleeding was preventable or potentially preventable in 109 of the 241 affected patients (45.2%).We have developed a useful, reliable tool for evaluating the preventability of VKA associated bleeding. Application of the scale in a prospective study revealed that a high proportion of VKA-associated bleeding events in hospitalized, at-risk adult patients were preventable or potentially preventable. PMID- 27684802 TI - The optimal dose of dexmedetomidine added to an sufentanil-based analgesic regimen for postoperative pain control in spine surgery: A probit analysis study. AB - Postoperative spinal patients remain a challenge for provision of postoperative analgesia. Patient-controlled intravenous analgesia (PCIA) is a major method in reducing the severe pain after the surgery in our institution, but some adverse effects prevent the use of adequate dosage opioids.This study was determined using the probit analysis to investigate the optimal dose of dexmedetomidine (DEX) infusion for postoperative analgesia combined with sufentanil (SUF) in spine surgery.The dose of DEX needed to produce satisfactory analgesia conditions following combination of 3.0 MUg/kg SUF in PCIA pump, which was diluted to 250 mL with a 4 mL/h as background infusion. Patients were recruited with age 35 to 65 years. The satisfactory criteria of postoperative analgesia were determined with a average satisfaction level of pain control, sedation, self-satisfaction, and adverse effects, among others. The dose of DEX was determined using the modified Dixon's up-and-down method (0.5 MUg/kg as a step size). The first patient was test at 3.0 MUg/kg DEX. The patient was assessed at 6, 12, 36 hours, and termination of PCIA following the continuous infusion of DEX-SUF mixture in PCIA after surgery.Twenty-five patients were enrolled by predetermined criteria. The optimal dose of DEX required for satisfactory analgesic was 4.33 (SD, 0.38) MUg/kg combined with 3.0 MUg/kg SUF via a PCIA volume of 250 mL by background infusion of 4 mL/h. Using probit analysis, the ED50 of DEX was 4.12 MUg/kg (95% confidence limits 3.74-4.52 MUg/kg) for satisfactory postoperative analgesic in spine surgery, the ED95 of DEX was 4.85 MUg/kg (95% confidence limits 4.48-7.13 MUg/kg). There was no report of somnolence or respiratory depression, relevant bradycardia or hypotension, or over sedation in this study.The optimal dose of DEX was 4.33 (0.38) MUg/kg combined with 3.0 MUg/kg SUF diluted to 250 mL with a background infusion of 4 mL/h for satisfactory analgesic after spine surgery. From probit analysis, ED50 and ED95 of DEX were 4.12 MUg/kg (95% confidence limits 3.74-4.52 MUg/kg) and 4.85 MUg.kg (95% confidence limits 4.48-7.13 MUg/kg), respectively. PMID- 27684803 TI - Cervicogenic headache alleviation after cervical coblation nucleoplasty: A prospective cohort study. AB - A degenerative cervical disc is a pain generator for headaches, and headaches can benefit from cervical prolapse surgery. However, as an alternative intervention for open cervical surgery, no study has reported whether headaches can benefit from cervical nucleoplasty.The objective of this study was to evaluate the efficacy of cervical coblation nucleoplasty in the treatment of cervicogenic headaches.In a prospective cohort study performed between December 2013 and August 2015, 20 patients with cervicogenic headaches undergoing cervical nucleoplasty for shoulder-arm pain were recruited into group C, and 20 patients with cervicogenic headaches undergoing lumbar nucleoplasty for low back pain, matched for age and sex, were recruited into group L. Cervicogenic pain was diagnosed according to the International Headache Society criteria. During the 24 month follow-up, pain visual analog scale (VAS) scores were collected as the primary outcomes, and significant pain relief rate, Neck Disability Index (NDI) headache scores, and Patients Satisfaction Index (PSI) scores were recorded as secondary outcomes to evaluate headache severity and physical function postoperatively.During the 24-month follow-up, a significant decrease in headache VAS scores was observed in group C but not in group L. NDI and PSI scores in group C were better than those in group L. In comparison with the final follow up, no significant differences in the NDI and PSI scores were found in all observations after surgery. In comparison to group L, >=50% pain relief was significantly better in group C. No serious complications were observed except for <=20% of ecchymoma at the needle insertion site.This prospective study indicated that cervicogenic headaches may benefit from nucleoplasty. PMID- 27684804 TI - A case report of pancreatic metastasis from synovial sarcoma successfully treated by metastasectomy with adjuvant chemotherapy. AB - INTRODUCTION: Synovial sarcoma is a malignant soft tissue sarcoma which arises near joints. The most frequent metastasis sites of synovial sarcoma are the lungs, lymph nodes, and bone. Pancreatic metastasis is quite rare; only 3 cases have been reported worldwide to date. We herein present the 4th case of pancreatic metastasis from synovial sarcoma. METHODS AND RESULTS: A 32-year-old man underwent extended excision of synovial sarcoma in the left pelvis and femur in 2009. In 2013, follow-up contrast-enhanced computed tomography revealed a 35 mm heterogeneously enhanced mass in the pancreas body. Endoscopic ultrasound guided fine needle aspiration of the mass revealed a diffuse proliferation of atypical spindle cells in a fascicular arrangement. Because the histology was quite similar to the resected specimen of synovial sarcoma in 2009, the mass was suspected to be a metastasis from synovial sarcoma. Laparoscopic distal pancreatectomy with adjuvant adriamycin/ifosfamide chemotherapy was subsequently performed. Synovial sarcoma-specific SS18-SSX1 (synovial sarcoma translocation, chromosome 18-synovial sarcoma X1) or SS18-SSX2 chimera mRNA was detected in the resected specimen, confirming the diagnosis of metastasis from synovial sarcoma. The patient did well for 30 months without recurrence. CONCLUSION: This case suggests that pancreatic metastasis from synovial sarcoma can be successfully treated by metastasectomy with adjuvant chemotherapy. PMID- 27684806 TI - Chemotherapy with or without estramustine for treatment of castration-resistant prostate cancer: A systematic review and meta-analysis. AB - BACKGROUND: Recently, increasing relevant studies researched the efficacy of castration resistant prostate cancer (CRPC) patients using chemotherapy with or without estramustine, in order to assess the efficacy and toxicity of combining estramustine with chemotherapy for the treatment of CRPC. METHODS: Relevant randomized clinical trials were systematically searched from the databases Pubmed, Embase, and Web of science up to April 1, 2016. Data were centrally extracted and analyzed from the previous studies by 2 independent reviewers. The primary endpoint was overall survival (OS) with pooled hazard ratios. Secondary endpoints were prostate-specific antigen (PSA) response and grade 3 or 4 toxicity using pooled odds ratios. Stata version 12.0 software was used for statistical analysis. RESULTS: Overall, this meta-analysis identified 9 eligible articles, including a total of 956 patients, who had been accrued between January 1, 1993 and December 1, 2010 and randomly divided into chemotherapy with estramustine and without estramustine. Chemotherapy (with or without estramustine) consisted of docetaxel, paclitaxel, ixabepilone, epirubicin, and vinblastine. Patients who received chemotherapy with estramustine had a better improvement in PSA response rate, comparing those without estramustine (OR = 1.84, 95% CI = 1.20-2.80). However, OS between the 2 groups indicated no significant differences (HR = 0.90, 95% CI = 0.77-1.05). Besides, these results of meta-analysis showed no obvious differences between these 2 groups in grade 3 or 4 adverse effects, including anemia (OR = 0.78, 95% CI = 0.38-1.57), neutropenia (OR = 0.91, 95% CI = 0.59 1.43), thrombocytopenia (OR = 0.68, 95% CI = 0.19-2.42), nausea (OR = 2.34, 95% CI = 0.81-6.72), vomiting (OR = 2.43, 95% CI = 0.69-8.51), diarrhea (OR = 3.45, 95% CI = 0.93-12.76), fatigue (OR = 0.67, 95% CI = 0.32-1.41), neuropathy (OR = 0.54, 95% CI = 0.21-1.44), allergic reaction (OR = 1.60, 95% CI = 0.37-6.84), thromboembolic event (OR = 2.18, 95% CI = 0.86-5.51), and edema (OR = 1.02, 95% CI = 0.18-5.95). CONCLUSIONS: This meta-analysis indicated chemotherapy with additional estramustine increased the PSA response rate. However, OS and grade 3 or 4 toxicity were not improved for these patients with CRPC. PMID- 27684805 TI - Reversible splenial lesion syndrome associated with lobar pneumonia: Case report and review of literature. AB - BACKGROUND: Reversible splenial lesion syndrome (RESLES) is a rare clinico radiological disorder with unclear pathophysiology. Clinically, RESLES is defined as reversible isolated splenial lesions in the corpus callosum, which can be readily identified by magnetic resonance imaging (MRI) and usually resolve completely over a period of time. RESLES could be typically triggered by infection, antiepileptic drugs (AEDs), poisoning, etc. More factors are increasingly recognized. METHODS AND RESULTS: We reported herein an 18-year-old female patient with lobar pneumonia who developed mental abnormalities during hospitalization. An isolated splenial lesion in the corpus callosum was found by head MRI and the lesion disappeared 15 days later. Based on her clinical manifestations and radiological findings, she was diagnosed with lobar pneumonia associated RESLES. We further summarize the up-to-date knowledge about the etiology, possible pathogenesis, clinical manifestations, radiological features, treatment, and prognosis of RESLES. CONCLUSION: This report contributes to the clinical understanding of RESLES which may present with mental abnormalities after infection. The characteristic imaging of reversible isolated splenial lesions in the corpus callosum was confirmed in this report. The clinical manifestations and lesions on MRI could disappear naturally after 1 month without special treatment. PMID- 27684807 TI - Early risk prognosis of free-flap transplant failure by quantitation of the macrophage colony-stimulating factor in patient plasma using 2-dimensional liquid chromatography multiple reaction monitoring-mass spectrometry. AB - Although great success of microvascular free-flap transplantation surgery has been achieved in recent years, between 1.5% and 15% of flaps are still lost due to vascular occlusion. The clinical challenge remains to salvage a transplant in the case of vascular complications. Since flap loss is devastating for the patient, it is of utmost importance to detect signs of complications or of conspicuities as soon as possible. Rescue success rates highly depend on early revision. In this study, we collected blood samples during transplantation surgery from either the contributory artery or the effluent vein of the flap and applied a targeted mass spectrometry-based approach to quantify 24 acute phase proteins, cytokines, and growth factors in 63 plasma samples from 21 hospitalized patients, generating a dataset with 9450 protein concentration values. Biostatistical analyses of the targeted plasma protein concentrations in all 63 plasma samples showed that venous concentrations of macrophage colony-stimulating factor (M-CSF) provided the highest accuracy for discriminating patients with either clinical conspicuities or complications from control individuals. Using 21.33 ng/mL of M-CSF as the diagnostic threshold when analyzing venous blood plasma samples, the assay obtained a sensitivity of 0.93 and a specificity of 0.85 with an area under the curve value of 0.902 in the receiver operating characteristic analysis. Overall, our results indicate that M-CSF is a potential molecular marker for early risk prognosis of free-flap transplant failure. PMID- 27684808 TI - Performance of obesity indices for screening elevated blood pressure in pediatric population: Systematic review and meta-analysis. AB - BACKGROUND: Hypertension is closely related with obesity in pediatric population. Obesity indices were used for screening elevated blood pressure (BP) in children and adolescents. The present study was to perform a meta-analysis to assess the performance of obesity indices, body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), for identifying elevated BP in children and adolescents. METHODS: Data sources were PubMed, EMBASE, Web of Science, Cochrane, and SCOPUS up to May 2016. Studies providing measures of diagnostic performance of obesity indices and using age-, sex-, and height-specific BP 95% as reference standard (the definition of United State Fourth Report) were included. We extracted available data on true-positive, false-positive, true-negative, and false-negative to construct a 2 * 2 contingency table and computed the pooled summary statistics for the sensitivities and specificities to estimate the diagnostic performance. RESULTS: Nine eligible studies that evaluated 25,424 children and adolescents aged 6 to 18 years were included in the meta-analysis. The pooled sensitivities were 42% (BMI), 42% (WC), and 43% (WHtR). The pooled specificities were 80% (BMI), 75% (WC), and 77% (WHtR). The areas under the curve (AUCs) of obesity indices were 0.7780 (BMI), 0.7181 (WC), and 0.6697 (WHtR), respectively. In this meta-analysis, the BP measurements were based on 3 visits in only 1 study. The prevalence of hypertension may be overestimated in these studies. CONCLUSIONS: The present meta-analysis showed that the performance of obesity indices for identifying elevated BP was poor. Our findings do not support the performance of WC and WHtR is superior to BMI to help identify children with elevated BP. PMID- 27684809 TI - Polidocanol versus glucose in the treatment of telangiectasia of the lower limbs (PG3T): Protocol for a randomized, controlled clinical trial. AB - BACKGROUND: Telangiectasias are defined as small venules abnormally dilated, located in the intradermal portion of the skin, of reddish or bluish tinge, their diameter not exceeding 1 mm; they are classified by the American Venous Forum as mild venous disease CEAP C1. Conventional treatment consists of chemical sclerotherapy, considered a minimally invasive technique with rapid clinical recovery. A wide variety of sclerosing solutions can be used for this purpose. METHODS/DESIGN: This project intends to include 96 patients that will be randomized to a triple-blind study. Inclusion criteria are women between 18 and 65 years, with telangiectasia on the lateral thigh. Male patients, female patients with chronic venous disease CEAP 2 to 6, women with allergies, pregnant, breastfeeding, with any type of skin problems or any decompensated clinical disease will be excluded. All patients included will be submitted to venous ultrasound mapping in order to rule out venous disease not clinically visible, deep venous system insufficiency, and insufficiency of the ostial valve of the great saphenous vein. One group will be treated with glucose 75% solution and the other will receive polidocanol 0.2% diluted in glucose 70%. Each patient will receive only 1 treatment session in 1 single member. The volume of sclerosing solution will not exceed 5 mL and the treatment area will be limited to a region of 150 cm on the lateral thigh. Clinical follow-up will be: 1 initial visit, when the clinical report will be filled; photographic record and treatment with sclerotherapy (D0); follow-up visits after 7 and 60 days (D7 and D60, respectively), always with clinical and photographic documentation. DISCUSSION: The project intends to evaluate the efficacy and safety of sclerotherapy in eliminating telangiectasia in a predetermined area in order to establish efficacy and safety parameters for the treatments presented. CONCLUSION: This protocol for clinical trial will provide date to determine the efficacy and safety of sclerotherapy with the solutions presented. TRIAL REGISTRATION IDENTIFIER: ClinicalTrial.gov NCT02657252 Date: 01/12/2016 (retrospectively registered). PMID- 27684810 TI - Patterns of lymph node metastasis in locally advanced cervical cancer. AB - The aim of this study was to investigate patterns and locations of lymph node metastasis in locally advanced cervical cancers.A total of 244 consecutive patients with stage IIb cervical cancer were retrospectively evaluated. Contrast enhanced CT scans were used for lymph node grading. Lymph nodes with the shortest axis (>1 cm) were categorized as positive and those between 0.5 and 1 cm were categorized as suspicious. All lymph nodes (LNs) were also classified by their anatomic locations.Nine hundred thirty-one LNs (136 positive and 795 suspicious) were identified. Sixty-three (25.8%) patients had positive LNs, and 153 (62.7%) patients had only suspicious LNs. The metastatic pattern was predictable traveling from level 1 (external iliac, internal iliac, obturator, and mesorectum groups) through level 2 (common iliac and presacral groups) to level 3 (para aortic groups). In most groups, LNs were located within 1.0 cm of main blood vessels. Our novel findings were: presacral LNs metastases were rare (2/244, 0.82%); the left common iliac group (LCI) had significantly more enlarged nodes than the right common iliac group (P = 0.00); the LCI and left down-para-aortic group were further away from blood vessels than expected (1.2 cm and 1.4 cm, respectively); no additional margin was needed in anterolateral direction for external iliac groups.The lymph node metastatic patterns are relatively predicable. Different expansions from vessels should be used to include LNs for different groups. Presacral nodes metastases are rare, and further study is warranted to see whether this region can be excluded from nodal CTV. PMID- 27684811 TI - Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT: A retrospective diagnostic accuracy study. AB - This study proposed to determine whether in vivo iodine concentration measurement by single-source dual energy (SSDE) CT can improve differentiation between benign and malignant thyroid nodules. In total, 53 patients presenting with thyroid nodules underwent SSDE CT scanning. Iodine concentrations were measured for each nodule and normal thyroid tissue using the GSI-viewer image analysis software. A total of 26 thyroid nodules were malignant in 26 patients and confirmed by surgery; 33 nodules from 27 patients were benign, with 10 confirmed by surgery and others after follow-up. Iodine concentrations with plain CT were significantly lower in malignant than benign nodules (0.47 +/- 0.20 vs 1.17 +/- 0.38 mg/mL, P = 0.00). Receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.93; with a cutoff of 0.67, iodine concentration showed 92.3% sensitivity and 88.5% specificity in diagnosing malignancy. Iodine concentration obtained by enhanced and plain CT were significantly higher in malignant than benign nodules (9.05 +/- 3.35 vs 3.46 +/- 2.24 mg/mL, P = 0.00). ROC curve analysis showed an AUC of 0.93; with a cutoff value of 3.37, iodine concentration displayed 78% sensitivity, 95% specificity in diagnosing malignancy. Combining unenhanced with enhanced iodine concentrations, the diagnostic equation was: Y = -8.641 * unenhanced iodine concentration + 0.663 * iodine concentration. ROC curve showed an AUC of 0.98 (95% CI, 0.94, 1.00). With Y >= -2 considered malignancy, diagnostic sensitivity and specificity were 96%, 96.3%, respectively. This study concluded that SSDE CT can detect the differences in iodine uptake and blood supply between benign and malignant thyroid lesions. PMID- 27684812 TI - The relationships among Dermatophagoides pteronyssinus exposure, exhaled nitric oxide, and exhaled breath condensate pH levels in atopic asthmatic children. AB - This study examined seasonal changes in indoor Dermatophagoides pteronyssinus 1 (Der p 1)/Blattella germanica 1 (Bla g 1) antigen concentrations in the homes of atopic asthmatic and atopic nonasthmatic children. Possible associations between environmental allergen exposure and levels of exhaled breath indices were also evaluated.A total of 38 atopic children were recruited for this cross-sectional study: 22 were asthmatic and 16 were nonasthmatic. Home visits were conducted for indoor air and dust sampling each season. Exhaled nitric oxide (eNO)/spirometric measurements were taken and exhaled breath condensate (EBC) was collected after sampling of the domestic environment.The highest Der p 1 concentrations were on the top of mattresses in the homes of recruited children. The floors of kitchens and living rooms had the highest Bla g 1 concentrations in the homes of atopic asthmatic children. A positive correlation was found between Der p 1 exposure of mattress, bedroom floor, and living room floor and eNO levels in the atopic asthmatic children. The Der p 1 concentrations on the surfaces of mattress and bedroom floor were positively related to high eNO levels in the atopic asthmatic children after adjusting for season. No association was found between Der p 1 exposure and EBC pH values in the recruited children.A positive correlation was found between Der p 1 exposure and high eNO levels in atopic asthmatic children, especially in Der p 1 exposure of mattress and bedroom floor. PMID- 27684813 TI - Training on an inexpensive tablet-based device is equally effective as on a standard laparoscopic box trainer: A randomized controlled trial. AB - BACKGROUND: The aim of the study was to assess whether an inexpensive tablet based box trainer (TBT) is at least equally effective compared with a standard box trainer (SBT) to learn basic laparoscopic skills (BLS). BLS training outside the operating room has been shown to be beneficial for surgical residency. However, simulation trainers are expensive and are not consistently available in all training centers. Therefore, TBT and other homemade box trainers were developed. METHODS: Medical students were randomized to either a TBT or an SBT and trained 4 fundamentals of laparoscopic surgery (FLS) tasks for 1 hour twice a week for 4 weeks. A baseline test before the training period and a posttraining test were performed. All students then completed a questionnaire to assess their assigned box trainer. The primary outcome measure was the improvement in total test scores. Improvement in the scores for the 4 individual FLS tasks was chosen as a secondary outcome measure. RESULTS: Thirty-two medical students were recruited. Baseline test scores did not differ significantly between the groups. BLS improved significantly in both groups for the total score and for all 4 tasks separately. Participants in the TBT group showed a greater improvement of total scores than those in the SBT group, although this did not reach statistical significance; noninferiority of the TBT compared with the SBT concerning the improvement of total scores could be demonstrated. Regarding the individual FLS tasks, noninferiority of the TBT could be shown for the pattern cutting and the suturing with intracorporeal knot-tying task. The acceptance of the TBT by the trainees was very good. CONCLUSION: Learning BLS on a homemade TBT is at least equally effective as on an SBT, with the advantage of being very cost saving. Therefore, this readily available box trainer may be used as an effective, flexible training device outside the operating room to improve accessibility to simulation training. PMID- 27684814 TI - Undiagnosed connective tissue diseases: High prevalence in pulmonary arterial hypertension patients. AB - Among different subgroups of pulmonary arterial hypertension (PAH), those associated with connective tissue diseases (CTDs) have distinct hemodynamic and prognostic features; a correct etiologic diagnosis is thus mandatory.To estimate frequency and prognosis of previously undiagnosed CTDs in a suspect idiopathic (i) PAH cohort.Consecutive patients with PAH confirmed by right heart catheterization referred at the Cardiology Division of our Hospital without a previous rheumatological assessment or the occurrence of other conditions explaining PAH were checked for CTD by a clinical, laboratory, and instrumental evaluation. Survival in each group has also been analyzed.In our study 17 of 49 patients were classified as CTD-PAH, corresponding to a prevalence (95% CI) of 34.7% (21.7-49.6%). ANA positivity had 94% (71.3-99.9%) sensitivity and 78.1% (60 90.7%) specificity for a diagnosis of CTD-PAH; Raynaud phenomenon (RP) showed 83.3% (51.6-97.9%) sensitivity and 100% (90.5-100%) specificity for the diagnosis of Systemic Sclerosis (SSc)-PAH. At diagnosis, SSc patients were older and had a lower creatinine clearance compared with iPAH and other CTD-PAH. After a median follow-up of 44 (2-132) months, 18 of 49 (36.7%) patients died: 31.2% in the iPAH group, 20% in the CTD-, and 58.3% in the SSc-PAH group. Mortality was significantly higher in SSc-PAH (HR 3.32, 1.11-9.95, P <0.05) versus iPAH.We show a high prevalence of undiagnosed CTDs in patients with iPAH without a previous rheumatological assessment. All patients with RP were diagnosed with SSc. Our data stress the importance of a rheumatological assessment in PAH, especially because of the unfavorable prognostic impact of an associated SSc. PMID- 27684815 TI - Rapid onset of radiation maculopathy after whole-brain radiation therapy: A case report. AB - BACKGROUND: Radiation maculopathy is a phenomenon that occurs after radiation exposure. The rapid onset of unilateral macular atrophy without peripheral retinopathy after radiation has rarely been described. METHODS: A case report and literature review. RESULTS: We report a case of stage 4 non-small cell lung cancer under targeted therapy using Gefitinib who presented with severely impaired visual acuity related to rapid onset of unilateral macular atrophy and diminished photoreceptor inner segment/outer segment (IS/OS) junction 1 month after whole-brain radiation therapy. The fundus fluorescein angiography revealed an enlarged diamond-shaped clear-cut foveal avascular zone in the macula without peripheral retinal vascular changes that differed from typical radiation retinopathy. We confirmed the diagnosis by evaluating the total radiation dosage and by excluding target therapy-induced maculopathy based on a review of the medical literature. CONCLUSION: Current therapeutic interventions for macular atrophy after radiation therapy remain a challenge. Vasodilators or antiplatelet medication may be beneficial; however, long-term follow-up is needed. Further studies are required to support the use of early aggressive therapy for the prevention of radiation retinopathy. PMID- 27684816 TI - Tc-99m-ECD SPECT as the measure for therapeutic response in patients with cobalamin deficiency: Two case reports. AB - BACKGROUND: Cobalamin (Cbl) is an essential vitamin for human health. While an increasing body of evidence supports the negative impact of Cbl deficiency on cognition, the causality has yet to be determined, and the reported therapeutic responses after Cbl supplement therapy have been inconsistent. Besides, few reports have described neuroimaging characteristics associated with the therapeutic response. METHODS: To describe and compare technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT) findings in 2 patients with Cbl deficiency with distinct therapeutic responses. RESULTS: Case 1 scored 12/30 in the mini-mental state examination (MMSE) and 34/100 in the cognitive abilities screening instrument (CASI). Profound deficits in mental manipulation, drawing, short-term/long-term memory, and verbal fluency were noted. Case 2 scored 24/30 in the MMSE and 78/100 in the CASI, mainly due to impaired mental manipulation, abstract thinking, and borderline performance in short-term memory and verbal fluency. While both cases showed widespread hypoperfusion within bilateral frontotemporal regions and thalamus on Tc-99m-ECD SPECT, Case 2 demonstrated relatively preserved radio-uptake in the frontal regions, especially the anterior cingulate cortex (ACC) and prefrontal cortex (PFC), consistent with the better therapeutic response (Case 1: 12/30 to 11/30 in the MMSE; Case 2: 24/30 to 28/30 in the MMSE). CONCLUSION: Given that the ACC integrates the limbic system and frontosubcortical circuits and the PFC governs executive function, the extent and severity of hypofrontality may be responsible for the worse prognosis. Our Tc-99m-ECD SPECT observations revealed that the negative impact on cerebral metabolic tone is relevant to the severity of Cbl deficiency, and the functional integrity of the ACC and PFC is highly associated with the preservation of global cognitive function in our cases with Cbl deficiency. PMID- 27684817 TI - Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His. AB - Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aalpha chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS-PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aalpha chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen. PMID- 27684818 TI - Chest CT with iterative reconstruction algorithms for airway stent evaluation in patients with malignant obstructive tracheobronchial diseases. AB - The aim of the study was to investigate the image quality of low-dose CT images with different reconstruction algorithms including filtered back projection (FBP), hybrid iterative reconstruction (HIR), and iterative model reconstruction (IMR) algorithms by comparison of routine dose images with FBP reconstruction, in patients with malignant obstructive tracheobronchial diseases.In total, 60 patients (59 +/- 9.3 years, 37 males) with airway stent who are randomly assigned into 2 groups (routine-dose [RD] and low-dose [LD] group, 30 for each) underwent chest CT on a 256-slice CT (RD-group 120 kV, 250 mAs, LD-group 120 kV, 120 mAs). Images were reconstructed with filtered back projection (FBP) algorithm in the RD group, whereas with FBP, HIR and IMR algorithms in the LD group. Effective radiation dose of both groups was recorded. Image-quality assessment was performed by 2 radiologists according to structure demarcation near stents, artifacts, noise, and diagnostic confidence using a 5-point scale (1 [poor] to 5 [excellent]). Image noise and CNR were measured.The effective radiation dose of LD group was reduced 52.7% compared with the RD group (10.8 mSv +/- 0.58 vs 5.1 mSv +/- 0.26, P = 0.00). LD-IMR images enabled lowest image noise and best subjective image quality scores of all 4 indices, when compared with RD images reconstructed with FBP (RD-FBP) images (all P < 0.05). LD images reconstructed with and with HIR (LD-HIR) images enabled higher score in subjective image quality of artifacts (P < 0.05), whereas it showed no difference in the other subjective image-quality indices and image noise. Significant higher image noise and lower score of subjective image quality were observed in LD-FBP images (all P < 0.05).Both IMR and HIR improved image quality of low-dose chest CT by comparison of routine dose images reconstructed with FBP. Meanwhile, IMR allows further image quality improvement than HIR. PMID- 27684820 TI - 3-Dimensional shear wave elastography of breast lesions: Added value of color patterns with emphasis on crater sign of coronal plane. AB - Color patterns of 3-dimensional (3D) shear wave elastography (SWE) is a promising method in differentiating tumoral nodules recently. This study was to evaluate the diagnostic accuracy of color patterns of 3D SWE in breast lesions, with special emphasis on coronal planes.A total of 198 consecutive women with 198 breast lesions (125 malignant and 73 benign) were included, who underwent conventional ultrasound (US), 3D B-mode, and 3D SWE before surgical excision. SWE color patterns of Views A (transverse), T (sagittal), and C (coronal) were determined. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were calculated.Distribution of SWE color patterns was significantly different between malignant and benign lesions (P = 0.001). In malignant lesions, "Stiff Rim" was significantly more frequent in View C (crater sign, 60.8%) than in View A (51.2%, P = 0.013) and View T (54.1%, P = 0.035). AUC for combination of "Crater Sign" and conventional US was significantly higher than View A (0.929 vs 0.902, P = 0.004) and View T (0.929 vs 0.907, P = 0.009), and specificity significantly increased (90.4% vs 78.1%, P = 0.013) without significant change in sensitivity (85.6% vs 88.0%, P = 0.664) as compared with conventional US.In conclusion, combination of conventional US with 3D SWE color patterns significantly increased diagnostic accuracy, with "Crater Sign" in coronal plane of the highest value. PMID- 27684821 TI - Patients with end-stage renal disease were at an increased risk of hospitalization for acute diverticulitis. AB - Patients with end-stage renal disease (ESRD) show a high incidence of bacterial translocation and impaired gastrointestinal motility. The intestinal tract is believed to be the most crucial source of translocated bacteria. To evaluate the risk of colonic diverticulitis in patients with ESRD, we conducted a nationwide population-based cohort study. Patients who met the following 3 criteria were defined as patients with ESRD: patients diagnosed with ESRD who received regular hemodialysis between 2000 and 2005, patients who received hemodialysis for more than 90% of the time during the observation period (2000-2011), and patients with no prior history of hemodialysis between 1997 and 1999. We matched every patient with ESRD with 1 matched control on the basis of propensity scores. The first diagnosis of diverticulitis (ICD-9-CM codes 562.11 and 562.13) within the follow up period was defined as the primary endpoint. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated using the patients in the control group as the reference. We included 32,547 and 32,547 patients in the ESRD and matched control cohorts, respectively. The 12-year cumulative incidence of acute colonic diverticulitis for patients with ESRD was significantly higher than that for the controls (P < 0.001). After adjustment for age, sex, comorbidities, and medication use, the HR of acute colonic diverticulitis in the ESRD cohort was 11.20 times greater than that in the control cohort (95% CI: 8.14-15.42). The results indicated that patients with ESRD are at an increased risk for acute colonic diverticulitis. PMID- 27684819 TI - Impact of alcohol consumption and body mass index on mortality from nonneoplastic liver diseases, upper aerodigestive tract cancers, and alcohol use disorders in Korean older middle-aged men: Prospective cohort study. AB - Alcohol use is a leading risk factor for the global disease burden including liver diseases. However, the combined effect of alcohol use and body mass index (BMI) on alcohol-related diseases has seldom been examined. We examined whether alcohol consumption and BMI could act together to increase mortality from nonneoplastic liver diseases, upper aero-digestive tract (UADT) cancers, and alcohol use disorders (AUD) in middle-aged Korean men.107,735 men (mean age, 58.8 years) participated in a postal survey in 2004 and were followed until 2010, by linkage to national death records. Hazard ratios (HRs) of cause-specific death were calculated after adjustment for confounders.Each 5-drink (approximately 45 g alcohol) higher weekly alcohol consumption was associated with increased mortality, by approximately 70% for nonneoplastic liver disease mortality (HR = 1.70, P < 0.001), approximately 60% for UADT cancer mortality (HR = 1.64, P < 0.001), and approximately 70% for AUD mortality (HR = 1.71, P < 0.001). Generally, BMI was inversely associated with these alcohol-related diseases (HR per each 5 kg/m higher BMI = 0.18-0.46, P < 0.001 for each cause), while, in participants with BMI >=25 kg/m, each 5 kg/m higher BMI was also associated with an elevated mortality from nonneoplastic liver diseases of approximately 150% (HR = 2.52, P = 0.001). Men with BMI < 21 kg/m and weekly alcohol consumption >=14 drinks showed markedly higher mortality from nonneoplastic liver diseases (HR = 5.7), alcoholic liver diseases (HR = 9.3), UADT cancers (HR = 10.5), and esophageal cancer (HR = 15.5), compared to men drinking less than 1 drink/wk with BMI >=25 kg/m. The combined effect of low BMI and high weekly alcohol consumption was 2.25- to 3.29-fold greater than the additive effect of each factor for these alcohol-related diseases (P < 0.05 for each cause).Alcohol consumption and low BMI were related to deaths from nonneoplastic liver diseases, UADT cancers, and AUD, with evidence of a supra-additive combined effect of both factors. High BMI was also related to deaths from nonneoplastic liver diseases. Men with a low BMI (<23 kg/m) are suggested to be prone to the harmful effects of alcohol. PMID- 27684822 TI - Disseminated cysticercosis: clinical spectrum, Toll-like receptor-4 gene polymorphisms and role of albendazole: A prospective follow-up of 60 cases with a review of 56 published cases. AB - In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India.Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available.There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment.Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in 27 patients. Of the 4 deaths recorded, 3 had a heavy parasitic load and died after praziquantel therapy.Toll-like receptor-4 gene polymorphisms are associated with an increased susceptibility to disseminated cysticercosis, in the Indian population. Albendazole treatment seems to reduce the lesion load and improve symptoms. PMID- 27684823 TI - Clinical evaluation of deep anterior lamellar keratoplasty using glycerol cryopreserved corneal tissues for refractory herpetic stromal keratitis: An observational study. AB - The study aimed to evaluate the therapeutic effects of deep anterior lamellar keratoplasty (DALK) using glycerol-cryopreserved corneal tissues (GCCTs) in patients with refractive herpes simplex keratitis (HSK). This article was a retrospective, noncomparative, and interventional case series. Patients with HSK underwent DALK using GCCTs at Shanghai Tongji Hospital from 2012 to 2015. The best spectacle corrected visual acuity, recurrent inflammation, graft status, postoperative central graft thickness, and pre/postoperative complications were detected. The follow-up ranged from 24.4 +/- 5.6 months (range: 16-38 months). Overall, the best spectacle corrected visual acuity was increased from HM/10 cm to 0.15 before surgery to 0.41 +/- 0.14 (range: 0.1-0.8; P < 0.05) at 12 months postoperatively. Intraoperative microperforation occurred in 4 eyes (14.81%), and rejection episodes were encountered in 3 of 27 eyes (11.1%), and all of the eyes reversed. HSK recurred in 2 eyes (7.41%), 1 eye with repeated recurring HSK, and eventually led to perpetual corneal opacity and the patient refused a retransplantation. The mean entire corneal thickness was 0.519 +/- 0.018 mm (range: 0.5-0.56 mm) and the mean graft thickness was 0.405 +/- 0.033 mm (range: 0.35-0.47 mm) in the final follow-up. The DALK using GCCTs was proven to be an effective and safe therapy in treating refractory HSK. PMID- 27684824 TI - Diagnostic performance of gadoxetic acid (Primovist)-enhanced MR imaging versus CT during hepatic arteriography and portography for small hypervascular hepatocellular carcinoma. AB - To compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI) with that of computed tomography (CT) during hepatic arteriography and arterial portography (CT HA/AP) for detecting hepatocellular carcinoma (HCC) from small hypervascular nodules.This retrospective study included 38 patients with 131 hypervascular nodules (<=2 cm) who had underwent MRI and CT HA/AP within a 2-week interval. Two observers analyzed MRI while other 2 observers analyzed CT HA/AP. Thereafter, MRI observers reviewed the CT HA/AP and magnetic resonance (MR) images again using both modalities. HCC was diagnosed by pathologic or imaging studies according to American Association for the Study of Liver Diseases (AASLD) criteria. Alternative free-response receiver operating characteristic (ROC) analysis was performed on a lesion-by-lesion basis. Diagnostic accuracy (area under the ROC curve [Az]), sensitivity, specificity, and positive and negative predictive values were calculated.The pooled Az was significantly higher for the combined modalities (0.946) than for MRI alone (0.9, P = 0.004), and for MRI than for CT HA/AP alone (0.827, P = 0.0154). Subgroup analysis for HCC <=1 cm showed the sensitivity of the combined modalities (79.4%) was significantly higher than for MRI (52.9%) and CT HA/AP alone (50%) (both, P < 0.005). The specificity of the combined modalities was not different from MRI alone (98.8% vs. 97.3%, P = 0.5), but was significantly higher than for CT HA/AP alone (98.8% vs. 92.5%, P = 0.022).Hypervascular HCCs >1 to 2 cm can be diagnosed sufficiently by MRI. The combined modalities increased the diagnostic accuracy of HCCs <=1 cm, compared with MRI or CT HA/AP alone. PMID- 27684825 TI - Atorvastatin inhibits insulin synthesis by inhibiting the Ras/Raf/ERK/CREB pathway in INS-1 cells. AB - BACKROUND: Type 2 diabetes has become a global epidemic disease. Atorvastatin has become a cornerstone in the prevention and treatment of atherosclerosis. However, increasing evidence showed that statins can dose-dependently increase the risk of diabetes mellitus. The mechanism is not clear. OBJECTIVE: The Ras complex pathway (Ras/Raf/extracellular signal-regulated kinase [ERK]/cAMP response element binding protein [CREB]) is the major pathway that regulates the gene transcription. Except for the inhibition of cholesterol synthesis by inhibiting the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-COA) reductase, statins can also downregulate the phosphorylation of a series of downstream substrates including the key proteins of the Ras complex pathway, therefore may inhibit the insulin syntheses in pancreatic beta cells. In our study, we investigated the inhibitory effect and the underlying mechanism of atorvastatin on insulin synthesis in rat islets. METHODS: Islets were isolated from Wistar rats and cultured in Roswell Park Memorial Institute (RPMI)-1640 medium. The insulin content in the medium was measured by radioimmunoassay before and after the treatment of 50 MUM atorvastatin. Effect of atorvastatin on the expression of insulin message Ribonucleic acid (mRNA) in pancreatic islet beta cells was also detected using quantitative real-time polymerase chain reaction. Western blotting was used to explore the possible role of the Ras complex pathway (Ras/Raf/ERK/CREB) in atorvastatin-inhibited insulin synthesis. The effects of atorvastatin on the binding of nuclear transcription factor p-CREB with CRE in INS-1 cells were examined via chromatin immunoprecipitation assay. RESULTS: Compared with the control group, the insulin level decreased by 27.1% at 24 hours after atorvastatin treatment. Atorvastatin inhibited insulin synthesis by decreasing insulin mRNA expression of pancreatic islet beta cells. The activities of Ras, Raf-1, and p-CREB in the Ras complex pathway were inhibited by 50 MUM atorvastatin in INS-1 cells in vitro. Moreover, 50 MUM atorvastatin reduced the binding of p-CREB with deoxyribonucleic acid (DNA) in INS-1 cells in vitro. CONCLUSION: Atorvastatin inhibits insulin synthesis in beta cells by inhibiting the activation of the Ras complex pathway. PMID- 27684826 TI - In vivo expansion and activation of gammadelta T cells as immunotherapy for refractory neuroblastoma: A phase 1 study. AB - INTRODUCTION: CD3+ gammadelta+ T cells comprise 2% to 5% of circulating T cells with Vgamma9Vdelta2+ cells the dominant circulating subtype. Vgamma9Vdelta2+ cells recognize non-peptide phosphoantigens and stress-associated NKG2D ligands expressed on malignant cells. Strategies that incorporate the tumoricidal properties of gammadelta T cells represent a promising immunotherapeutic strategy for treatment of solid malignancies including neuroblastoma (NB). In this prospective, non-randomized Phase I trial, we assessed whether circulating Vgamma9Vdelta2+ cells could be safely expanded using intravenous ZOL (Zoledronate [Zometa]) and subcutaneous Interleukin-2 (IL-2) in patients with refractory NB. METHODS: Patients 2 to 21 years of age with refractory neuroblastoma with no known curative therapeutic options received ZOL on day 1, and IL-2 on days 1 to 5 and 15 to 19 of each 28-day cycle (n = 4). Lymphocyte immunophenotyping was assessed weekly. Immunophenotyping studies from the treatment group were compared with healthy pediatric controls (n = 16; range, 5y-15y) and of untreated NB disease controls (n = 9; range, 4m-18y). RESULTS: Treatment was well tolerated with no unexpected grade 3 and 4 toxicities. Lymphocyte subset counts did not differ significantly between volunteers and disease controls with the exception of gammadelta+ T cell counts that were significantly higher in healthy volunteers (212 + 93 vs. 89 + 42, P = 0.05). Study patients showed increases in circulating gammadelta+ T cell count (3-10 fold) after the first week, increasing into the range seen in healthy volunteers (125 + 37, P = 0.1940). Interestingly, all ZOL + IL-2 treated patients showed significant increases in CD3+CD4+CD27CD127 T cells that rose weekly in 2 patients throughout the 4 weeks of observation (maximum 41% and 24% of total CD3+CD4+ T cells, respectively). CONCLUSIONS: In summary, combined ZOL and IL-2 is well tolerated and restored gammadelta+ T cell counts to the normal range with a moderate expansion of Natural Killer cells. Progressive increases in circulating CD4+ T cells with a regulatory phenotype cells may offset beneficial effects of this therapy. PMID- 27684827 TI - Motives of Dutch men who have sex with men for daily and intermittent HIV pre exposure prophylaxis usage and preferences for implementation: A qualitative study. AB - Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV negative men having sex with men (MSM).Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach.Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients' medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support.To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling. PMID- 27684828 TI - Pulmonary arterial hypertension in idiopathic inflammatory myopathies: Data from the French pulmonary hypertension registry and review of the literature. AB - Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients.All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH.Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment.By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06).Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone.Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement, peripheral microangiopathy, and anti-SSA positivity. The best therapeutic strategy for IIM-PAH remains to be defined. PMID- 27684829 TI - GABA+ levels in postmenopausal women with mild-to-moderate depression: A preliminary study. AB - BACKGROUND: It is increasingly being recognized that alterations of the GABAergic system are implicated in the pathophysiology of depression. This study aimed to explore in vivo gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and posterior-cingulate cortex (PCC) of postmenopausal women with depression using magnetic resonance spectroscopy (H MRS). METHODS: Nineteen postmenopausal women with depression and thirteen healthy controls were enrolled in the study. All subjects underwent H-MRS of the ACC/mPFC and PCC using the "MEGA Point Resolved Spectroscopy Sequence" (MEGA-PRESS) technique. The severity of depression was assessed by 17-item Hamilton Depression Scale (HAMD). Quantification of MRS data was performed using Gannet program. Differences of GABA+ levels from patients and controls were tested using one-way analysis of variance. Spearman correlation coefficients were used to evaluate the linear associations between GABA+ levels and HAMD scores, as well as estrogen levels. RESULTS: Significantly lower GABA+ levels were detected in the ACC/mPFC of postmenopausal women with depression compared to healthy controls (P = 0.002). No significant correlations were found between 17-HAMD/14-HAMA and GABA+ levels, either in ACC/mPFC (P = 0.486; r = 0.170/P = 0.814; r = -0.058) or PCC (P = 0.887; r = 0.035/ P = 0.987; r = -0.004) in the patients; there is also no significant correlation between GABA+ levels and estrogen levels in patients group (ACC/mPFC: P = 0.629, r = -0.018; PCC: P = 0.861, r = 0.043). CONCLUSION: Significantly lower GABA+ levels were found in the ACC/mPFC of postmenopausal women with depression, suggesting that the dysfunction of the GABAergic system may also be involved in the pathogenesis of depression in postmenopausal women. PMID- 27684830 TI - Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma: A retrospective matched case-control study. AB - To evaluate the treatment efficacies and toxicities of concurrent cetuximab-based bioradiotherapy (BRT) or cisplatin-based chemoradiotherapy (CRT) in locally advanced nasopharyngeal carcinoma. :Patients with previously untreated locally advanced nasopharyngeal carcinoma were matched into pairs, and enrolled into the study. All patients were given either BRT or CRT. Survival outcomes, toxicities, and prognostic factors were evaluated. :A total of 112 patients were enrolled. The 5-year overall survival was 79.3% and 79.5% in CRT and BRT arm, respectively (P = 0.797) and the 5-year DFS was 73.5% and 74.6%, respectively (P = 0.953). In toxicity analysis, CRT arm had more significant decrease in white blood cell, platelet, hemoglobin, and severe vomiting, while more severe skin reactions and mucositis were shown in BRT arm. :BRT was not less efficacious than traditional CRT. They lead to different aspects of toxicities. If patients cannot stand more severe toxicities caused by CRT, BRT could be an ideal alternative. PMID- 27684831 TI - Length to width ratio of the ductus venosus in simple screening for fetal congenital heart diseases in the second trimester. AB - Antenatal diagnosis of congenital heart disease (CHD) is still low even though screening was first introduced over 25 years ago. The purpose of our study was to determine the efficacy of a second-trimester prenatal ultrasonographic method of screening for CHD.From September 2012 to September 2013, the length and width of the fetal ductus venosus were measured sonographically in 1006 singleton fetuses, and the ratio of length to width was calculated. The accuracy of each fetal measurement and Doppler ultrasonography were determined. The standard fetal echocardiographic evaluations including 2-dimensional gray-scale imaging, color, and Doppler color flow mapping were performed. The transducer was aligned to the long axis of the fetal trunk to view the ductus venosus in its full length, including the inlet (isthmus) and outlet portions of the vessel. The diameters of the vessel inner wall and mid-point of the ductus venosus were measured using calipers. All scans and fetal measurements were conducted by a registered sonographer with more than 20 years of perinatal ultrasound screening experience.Of the 1006 singleton fetuses between 19 and 28 weeks' gestation, 36 had CHD. The ductus venosus length/width ratio (DVR) for the first CHD screening was extremely sensitive at 88.90%, with a specificity of 99.10% for the cardiac abnormalities included in this study. Chromosomal anomalies accompanied CHD in 0.4% (4/1006) of all cases and 11.11% (4/36) of the CHD cases.The DVR differed significantly between fetuses with CHD and normal fetuses during the second trimester. Careful assessment of the ratio should be a part of the sonographic examination of every fetus. In the case of a small DVR, advanced echocardiography and karyotype analysis should be performed. The ratio is a helpful tool for screening CHD abnormalities prenatally in the Chinese population. PMID- 27684832 TI - Abdominal obesity and structure and function of the heart in healthy male Koreans: The ARIRANG study. AB - Although central obesity is a more powerful predictor of cardiovascular disease (CVD) than general obesity, there is limited information on structural and functional changes of the heart in central obesity. Therefore, we evaluated the association between abdominal obesity and geometric and functional changes of the heart in healthy males. A total of 1460 healthy males aged 40 to 70 years without known CVD from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population were included. All individuals underwent conventional 2-dimensional echocardiography and tissue Doppler imaging to measure left atrial (LA) and left ventricle (LV) geometry and function. Increasing tertiles of waist circumference (WC) were associated with stepwise increases in LA volume, LV end-diastolic dimension, LV mass to height, deceleration time of E wave, and lower E/A ratio (all P trends <0.001). In multivariable logistic regression models, the odds ratios for LA enlargement, LV hypertrophy, LV enlargement, and diastolic dysfunction comparing the upper tertile of WC (>89 cm) to the lowest tertile (<82 cm) were 2.81 (95% confidence interval [CI] 2.24-3.54), 3.65 (95% CI 2.54-5.26), 4.23 (95% CI 2.61-6.87), and 1.75 (95% CI 1.37-2.22), respectively. LV ejection fraction and relative wall thickness were not increased with increasing WC. The association between WC and LA enlargement, LV enlargement, and diastolic dysfunction persisted after stratification by body mass index tertiles. Central obesity may be a stronger predictor than general obesity of geometric and functional changes in the LV and LA. PMID- 27684833 TI - Use of the GlideScope video laryngoscope for intubation during ex utero intrapartum treatment in a fetus with a giant cyst of the 4th branchial cleft: A case report. AB - INTRODUCTION: In fetuses who are predicted to be at risk of catastrophic airway obstruction at delivery, the ex utero intrapartum treatment (EXIT) procedure is useful for securing the fetal airway while maintaining fetal oxygenation via placental circulation. Factors, including poor posture of the fetus and physician, narrow visual field, and issues of contamination in the aseptic surgical field, make fetal intubation during the EXIT procedure difficult. Herein, we report our experience of the usefulness of the GlideScope video laryngoscope (GVL) for intubation during the EXIT procedure. SYMPTOMS AND CLINICAL FINDINGS: A 28-year-old woman presented with a fetus having a cystic neck mass diagnosed on prenatal ultrasound at 25 weeks of gestation. We planned the EXIT procedure in conjunction with cesarean delivery at 38 weeks of gestation, as the mass enlarged to 4.9 cm * 3.2 cm, protruded externally at the neck, and subsequently resulted in polyhydramnios. THERAPEUTIC INTERVENTION AND OUTCOMES: After induction of anesthesia using intravenous thiopental (300 mg), adequate uterine relaxation was achieved with sevoflurane (2.0-3.0 vol%) combined with continuous intravenous infusion of nitroglycerin (0.5-1.0 MUg/kg/min) for maintaining uteroplacental circulation. After hysterotomy, the head and right upper limb of the fetus were partially delivered, and fetal heart tones were monitored with a sterile Doppler probe. After oropharyngeal suctioning to improve the visual field, the fetus was intubated successfully using a sterile GVL by an anesthesiologist, and the passage of the endotracheal tube beyond the vocal cords was confirmed on the screen of the GVL system. Immediately after the fetal airway was definitely secured, the fetus was fully delivered with umbilical cord clamping. After delivery, nitroglycerine administration was ceased and sevoflurane administration was reduced to 0.5 minimum alveolar concentration. Additionally, oxytocin (10 units) and carbetocin (100 MUg) were administered for recovery of uterine contraction. Cesarean delivery was successfully performed without any problems, and the neonate successfully underwent surgery for removal of the neck mass under general anesthesia on the 7th day after delivery. The neonate is developing normally. CONCLUSION: The GVL approach may be a useful noninvasive approach for establishing a clear fetal airway during the EXIT procedure. PMID- 27684834 TI - Neutrophils assist the metastasis of circulating tumor cells in pancreatic ductal adenocarcinoma: A new hypothesis and a new predictor for distant metastasis. AB - During our research on circulating tumor cells (CTCs) derived from tumor-adjacent vessels in pancreatic ductal adenocarcinoma (PDAC), we found that CTCs are sometimes surrounded by white blood cells (WBCs) in blood. We hypothesize that such interaction between WBCs and CTCs in blood is a mechanism by which WBCs assist in the metastasis of CTCs. We present our laboratory finding, with our evaluation of the association between the neutrophil-to-lymphocyte ratio (NLR, the most investigated clinical parameter of WBCs) and distant metastasis after curative surgery in PDAC. The laboratory finding was presented through immunofluorescence. In the clinical segment, we performed a retrospective study on PDAC patients with distant metastasis after curative surgery who were referred to Peking University Third Hospital between 2005 and 2014. The data on the possible clinical factors were collected by a retrospective review of the patients' records. Immunofluorescence results showed that CTCs are surrounded by WBCs in tumor-adjacent vessels of PDAC patients. In the clinical segment, 112 (70%) of a total of 160 PDAC patients were found to have developed distant metastases after surgery; among the 112 patients, only 89 had entire data and were enrolled for further analysis (84.3% patients had liver metastasis). No significant association was found between the NLR and overall survival (hazard ratio [HR] = 1.027, 95% confidence interval [CI] 0.723-1.459, P = 0.88); however, a significant relationship between the NLR and distant metastasis after curative surgery was found on the univariate (HR = 1.641, 95% CI 1.058-2.545, P = 0.027) and multivariate analyses (HR = 2.15, 95% CI 1.279-3.615, P = 0.004). Neutrophils might assist in distant metastasis through interaction with CTCs in blood. Moreover, NLR is an effective predictor for distant metastasis after curative surgery for PDAC. PMID- 27684835 TI - Efficacy and tolerability of oxycodone versus fentanyl for intravenous patient controlled analgesia after gastrointestinal laparotomy: A prospective, randomized, double-blind study. AB - BACKGROUND: It has been suggested that oxycodone is effective in relieving acute postoperative pain. The aim of this study was to investigate the efficacy and tolerability of oxycodone (O) versus fentanyl (F), and the adequate potency ratio of oxycodone and fentanyl in patients with intravenous patient-controlled analgesia after gastric laparotomy. METHODS: In this double-blinded, randomized, controlled study, 60 patients undergoing elective gastric laparotomy were allocated to receive either oxycodone or fentanyl for postoperative intravenous patient-controlled analgesia (potency ratio 60:1). The patients received ketorolac 60 mg before the end of anesthesia and then continued with patient controlled analgesia for 48 hours postsurgery. Pain severity, side effects and respiration rate were recorded 30 minutes, 3, 6, 12, 24, and 48 hours after the surgery. Cumulative opioid requirements and patient satisfaction were also measured. RESULTS: The median consumption more than 48 hours after operation of oxycodone was 50 mg (range: 40.0-62.4 mg) and fentanyl was 0.8 mg (range: 0.6-1.1 mg), and the percentage of patients requiring rescue medication was not statistically significant. Numeric rating scores at rest and upon movement were significantly lower in group O than in F (P < 0.05). Whereas the incidences of adverse events were similar between the groups (33.3% vs 27.6%, P = 0.64), a significant higher sedation scores were found in patients given fentanyl at 30 minutes after the surgery (P = 0.04). CONCLUSION: Oxycodone was comparable to fentanyl in the relief of postoperative pain following gastric laparotomy. Oxycodone not only provides better postoperative pain relief and less sedation, but also there was a tendency toward more side effects with oxycodone. PMID- 27684837 TI - Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: A meta-analysis. AB - BACKGROUND: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. METHODS: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. RESULTS: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P < 0.00001) and an 18% reduction in RR (RR 0.82, 95% CI [0.73, 0.93], P = 0.002) in the subgroup without renal transplant recipients and patients undergoing regular hemodialysis separately. For the fatal stroke incidences, intensive-dose statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. CONCLUSION: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID- 27684836 TI - Postoperative adverse outcomes among physicians receiving major surgeries: A nationwide retrospective cohort study. AB - Outcomes after surgeries involving physicians as patients have not been researched. This study compares postoperative adverse events between physicians as surgical patients and nonhealth professional controls.Using reimbursement claims data from Taiwan's National Health Insurance Program, we conducted a matched retrospective cohort study of 7973 physicians as surgical patients and 7973 propensity score-matched nonphysician controls receiving in-hospital major surgeries between 2004 and 2010. We compared postoperative major complications, length of hospital stay, intensive care unit (ICU), medical expenditure, and 30 day mortality.Compared with nonphysician controls, physicians as surgical patients had lower adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of postoperative deep wound infection (OR 0.63, 95% CI 0.40-0.99; P < 0.05), prolonged length of stay (OR 0.68, 95% CI 0.62-0.75; P < 0.0001), ICU admission (OR 0.74, 95% CI 0.66-0.83; P < 0.0001), and increased medical expenditure (OR 0.80, 95% CI 0.73-0.88; P < 0.0001). Physicians as surgical patients were not associated with 30-day in-hospital mortality after surgery. Physicians working at medical centers (P < 0.05 for all), dentists (P < 0.05 for all), and those with fewer coexisting medical conditions (P < 0.05 for all) had lower risks for postoperative prolonged length of stay, ICU admission, and increased medical expenditure.Although our study's findings suggest that physicians as surgical patients have better outcomes after surgery, future clinical prospective studies are needed for validation. PMID- 27684839 TI - Comparison of minimally invasive plate osteosynthesis and conventional plate osteosynthesis for humeral shaft fracture: A meta-analysis. AB - BACKGROUND: The objective of this meta-analysis was to compare the efficacy and safety of minimally invasive plate osteosynthesis (MIPO) and conventional plate osteosynthesis (CPO) for humeral shaft fracture. METHODS: Potential academic articles were identified from the Cochrane Library, Medline (1966-2016.3), PubMed (1966-2016.3), Embase (1980-2016.3), and ScienceDirect (1966-2016.3). Gray studies were identified from the references of the included literature. Randomized controlled trials (RCTs) and non-RCT involving MIPO and CPO for humeral shaft fracture were included. Two independent reviewers performed independent data abstraction. I statistic was used to assess heterogeneity. Fixed or random effects model was used for meta-analysis. RESULTS: Two RCTs and 3 non RCTs met the inclusion criteria. There was a lower incidence of iatrogenic radial nerve palsy in patients with MIPO (P = 0.006). There was no statistically significant difference in in the risk of developing nonunion, delay union, malformation, screw loosening, infection, operation time, UCLA, and MEPS function score between the 2 groups. CONCLUSION: MIPO decreased incidence of iatrogenic radial nerve palsy and is an efficacy and safety technique for humeral shaft fracture. Due to the limited quality and data of the evidence currently available, more high-quality RCTs are required. PMID- 27684838 TI - Uncommon liver tumors: Case report and literature review. AB - BACKGROUND: Beside hepatocellular carcinoma, metastasis, and cholangiocarcinoma, the imaging findings of other relatively uncommon hepatic lesions are less discussed in the literature. Imaging diagnosis of these lesions is a daily challenge. In this article, we review the imaging characteristics of these neoplasms. METHODS: From January 2003 to December 2014, 4746 patients underwent liver biopsy or hepatic surgical resection in our hospital. We reviewed the pathological database retrospectively. Imaging of these lesions was reviewed. RESULTS: Imaging findings of uncommon hepatic lesions vary. We discuss the typical imaging characteristics with literature review. Clinical and pathological correlations are also described. Primary hepatic lymphoma consists only of 1% of the extranodal non-Hodgkin lymphoma, and is defined as the one involving only the liver and perihepatic lymph nodes within 6 months after diagnosis. Combined hepatocellular and cholangiocarcinoma (cHCC-CC) shares some overlapping imaging characteristics with both HCC and cholangiocarcinoma because of being an admixture of them. Angiosarcoma is the most common hepatic mesenchymal tumor and is hypervascular in nature. Inflammatory pseudotumor is often heterogeneous on ultrasonography and with enhanced septations and rims in the portovenous phase after contrast medium. Angiomyolipoma (AML) typically presents with macroscopic fat components with low signal on fat-saturated magnetic resonance imaging (MRI) and presence of drainage vessels. Intraductal papillary neoplasm of the bile duct (IPNB) is thought of as a counterpart to the pancreatic intraductal papillary mucinous neoplasm. Most of the IPNBs secrete mucin and cause disproportional dilatation of the bile ducts. Mucinous cystic neoplasm (MCN) contains proteinaceous and colloidal components without ductal communication and characterizes with hyperintensity on T1-weighted imaging. Other extremely rare lesions, including epithelioid hemangioendothelioma and inflammatory pseudotumor like follicular dendritic cell sarcoma, are also discussed. Hepatoblastoma and mesenchymal hamartoma, mostly in children, are also briefly reviewed as well. CONCLUSION: It is important for radiologists to be familiar with the typical imaging features of the uncommon hepatic neoplasms. If imaging findings are not typical or diagnostic, further biopsy is required. PMID- 27684840 TI - Association of CD14 -159 (-260C/T) polymorphism and asthma risk: an updated genetic meta-analysis study. AB - BACKGROUND: It has been reported that the cluster of differentiation 14 (CD14) gene -159C/T variant may be associated with asthma risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was designed to assess the precise association. METHODS: A systematic search in PubMed, Embase (Ovid), China National Knowledge Internet (CNKI), and Wan fang databases was conducted up to August 15, 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to pool the effect size. We used I to assess heterogeneity, and a funnel plot and Egger test to assess publication bias. RESULTS: In total, 34 studies involving 15,641 subjects were included in this meta-analysis. There was a statistically significant association between CD14 159C/T polymorphism and asthma risk observed in dominant model (TT+TC vs CC: OR = 0.86, 95% CI = 0.77-0.97, P = 0.012) and codominant model (TC vs CC: OR = 0.88, 95% CI = 0.78-0.99, P = 0.035) in adults. However, there may be no significant association between CD14 159C/T and atopic and nonatopic asthma risk. CONCLUSION: In summary, the overall results suggested that the CD14 -159C/T variant may decrease the risk of asthma susceptibility in adults. However, no significant association between CD14 159C/T and atopic and nonatopic asthma susceptibility was identified. More studies with larger sample size are needed to validate the findings from this study. PMID- 27684841 TI - The effectiveness and safety of tranexamic acid in bilateral total knee arthroplasty: A meta-analysis. AB - OBJECTIVE: A meta-analysis was performed to investigate the effectiveness and safety of tranexamic acid (TXA) for the treatment of blood loss after a bilateral total knee arthroplasty (TKA). METHODS: Patients prepared for bilateral TKA and intervention including TXA versus placebo were comprehensively retrieved from MEDLINE (PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from the time of the establishment of these databases to January 2016. The outcomes were all calculated by Stata 12.0 software. The continuous endpoints (total blood loss and blood loss in drainage) were calculated as mean difference (MD) and 95% confidence intervals (CIs). Binary variables (the need for transfusion, and the occurrence of deep venous thrombosis [DVT]) were calculated as relative risk (RR) with 95% CIs. RESULTS: Pooled results revealed that treatment with TXA associated with less need for transfusion (P = 0.000) and the value of Hb drop postoperatively (P = 0.290) after bilateral TKA. The results also indicated that TXA can decrease the total blood loss and blood loss in drainage after bilateral TKA (P < 0.05). Meanwhile, TXA can decrease the blood units transfused per patient by 1.23 U (P = 0.001). There is no statistically significant difference in terms of the occurrence of DVT between the 2 groups (P = 0.461). CONCLUSION: Based on the current evidence, TXA can decrease the need for transfusion and the total blood loss without increasing the occurrence of DVT, and its administration is recommended routinely in bilateral TKA. PMID- 27684842 TI - Uterus-like mass: A very rare and elusive entity a case report. AB - BACKGROUND: Uterus-like mass (ULM) is an extremely rare lesion. Gross morphology of ULM resembling a uterus. It can occur in various organs in the abdominal cavity, even in the spinal cord. The histogenesis of ULM remains uncertain. A number of hypotheses have been proposed including metaplasia, congenital anomaly, and heterotopia theory. METHODS: We describe a case of 43-year-old male presented with a complaint of acute low abdominal pain. Pelvic ultrasound found a large pelvic mass embedded in the broad ligament. RESULTS: The mass contains a variable thickness smooth muscle layer lined with endometrial glands and stroma which resembling a uterus. Eventually, the patient was diagnosed as ULM by histopathological examination. CONCLUSION: Except hypomenorrhea, the patient did not have any other associated abnormalities. We suggest this case supports the metaplasia theory that ULM is a benign mass formed by the proliferation of ectopic endometrial stromal cells or pluripotent mesenchymal cells of the 2nd Mullerian system. PMID- 27684843 TI - An association of platelet indices with blood pressure in Beijing adults: Applying quadratic inference function for a longitudinal study. AB - The quadratic inference function (QIF) method becomes more acceptable for correlated data because of its advantages over generalized estimating equations (GEE). This study aimed to evaluate the relationship between platelet indices and blood pressure using QIF method, which has not been studied extensively in real data settings.A population-based longitudinal study was conducted in Beijing from 2007 to 2012, and the median of follow-up was 6 years. A total of 6515 cases, who were aged between 20 and 65 years at baseline and underwent routine physical examinations every year from 3 Beijing hospitals were enrolled to explore the association between platelet indices and blood pressure by QIF method. The original continuous platelet indices were categorized into 4 levels (Q1-Q4) using the 3 quartiles of P25, P50, and P75 as a critical value. GEE was performed to make a comparison with QIF.After adjusting for age, usage of drugs, and other confounding factors, mean platelet volume was negatively associated with diastolic blood pressure (DBP) (Equation is included in full-text article.)in males and positively linked with systolic blood pressure (SBP) (Equation is included in full-text article.). Platelet distribution width was negatively associated with SBP (Equation is included in full-text article.). Blood platelet count was associated with DBP (Equation is included in full-text article.)in males.Adults in Beijing with prolonged exposure to extreme value of platelet indices have elevated risk for future hypertension and evidence suggesting using some platelet indices for early diagnosis of high blood pressure was provided. PMID- 27684844 TI - Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma. AB - BACKGROUND & OBJECTIVES: Telomere plays a critical role in the maintenance of genomic stability in eukaryotic chromosomes. More and more findings have shown that alteration in telomere length may involve in normal somatic cells and some diseases, however, whether the telomere length is associated with the development and/or progression of hepatic diseases remains poorly understood. METHODS: A case control study was employed to illustrate the correlation of relative telomere length (RTL) with chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). In this study, 152 patients with HCC, 212 patients with CHB, and 184 healthy controls were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood leukocytes, and fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect telomere repeated numbers and 36B4 copy numbers. The RTL was calculated by telomere repeat copy number to single-copy gene number ratio in each sample compared with a reference DNA sample. RESULTS: We found that the RTL in HCC group was the longest, followed by CHB group, and healthy control group was the shortest, showing significant statistical differences. When participants were categorized into longer and shorter group according to medium value in healthy controls, individuals who had longer RTL had a significant increased risk of CHB (odds ratio [OR]: 1.83, 95% confidence interval [CI]: 1.22-2.73) when the healthy control was used as the reference groups; furthermore, longer RTL also showed higher incidence of HCC (OR: 3.22, 95% CI: 2.01-5.17; OR: 1.58, 95% CI:1.03-2.41) when healthy control and CHB were used as the reference groups, respectively. When participants were categorized further into 4 groups according to quartile values of RTL in healthy controls, it showed that the longest RTL was also associated with an increased risk of CHB (OR: 2.09, 95% CI: 1.17-3.74) and HCC (OR: 4.31, 95% CI: 2.18-8.52; OR: 2.86, 95% CI: 1.53-5.34) when control and control/CHB group were used as the reference groups, respectively. CONCLUSION: Our results suggest that the alteration of telomere length in peripheral leukocytes might be involved in the hepatitis B virus infection and HCC events, and RTL might be a potential useful predictor of CHB and HCC. PMID- 27684845 TI - The prevalence and factors associate with vocal nodules in general population: Cross-sectional epidemiological study. AB - The purpose of this study was to analyze the prevalence of vocal nodules and to identify factors related with an increased risk for vocal nodules.This study was conducted using data from the Korean National Health and Nutrition Examination Survey 2008 to 2011. The subjects consisted of 19,636 men and women aged >=19 years. Related factors such as age, marital status, incomes, and education level were assessed in individual interviews, and health-related behaviors including smoking, alcohol, and activity were assessed with self-administered questionnaires. Also, examination survey such as laryngoscopy examination, basic physical examination, and blood sampling was conducted.The prevalence of vocal nodules was 1.31% (n = 258). Among variable factors, age, education level, and voice disorder were related with the presence of vocal nodules (P < 0.05). Other factors including sex, alcohol, smoking, physical activities, hypertension, obesity, waist circumference and metabolic syndrome, hypercholesterolemia, serum calcium, and vitamin D did not show any meaningful relationship with the presence of vocal nodules.This result may help reduce the incidence of vocal nodules and offer proper management for patients with vocal nodules, and may also facilitate efficient allocation of public health resources. PMID- 27684846 TI - Clinical significance of hyperhomocysteinemia in infective endocarditis: A case control study. AB - Blood coagulation plays a key role in the pathogenesis of infective endocarditis (IE). Conditions associated with thrombophilia could enhance IE vegetation formation and promote embolic complications.In this study, we assessed prevalence, correlates, and clinical consequences of hyper-homocysteinemia (h Hcy) in IE.Homocysteine (Hcy) plasma levels were studied in 246 IE patients and 258 valvular heart disease (VHD) patients, as well as in 106 healthy controls.IE patients showed Hcy levels comparable to VHD patients (14.9 [3-81] vs 16 [5-50] MUmol/L, respectively; P = 0.08). H-Hcy was observed in 48.8% of IE patients and 55.8% of VHD (P = 0.13). Vegetation size and major embolic complications were not related to Hcy levels. IE patients with h-Hcy had a higher prevalence of chronic kidney disease and a higher 1-year mortality (19.6% vs 9.9% in those without h Hcy; OR 2.21 [1.00-4.89], P = 0.05). However, at logistic regression analysis, h Hcy was not an independent predictor of 1-year mortality (OR 1.87 [95% CI 0.8 4.2]; P = 0.13).Our data suggest h-Hcy in IE is common, is related to a worse renal function, and may be a marker of cardiac dysfunction rather than infection. H-Hcy does not appear to favor IE vegetation formation or its symptomatic embolic complications. PMID- 27684847 TI - Dental arch dimensional changes after adenoidectomy or tonsillectomy in children with airway obstruction: A meta-analysis and systematic review under PRISMA guidelines. AB - BACKGROUND: Children with severe airway obstruction tend to have a vertical direction of growth, class II malocclusion, and narrow arches. Adenoidectomy and tonsillectomy were recommended for the promotion of balanced dentition growth in these children.The aim of this study was to determine the effect of adenoidectomy and tonsillectomy on the growth of dental morphology in children with airway obstruction. METHODS: A comprehensive search of the Medline, Embase, Web of science, and OVID databases for studies published through to January 17, 2016 was conducted. Prospective, comparative, clinical studies assessing the efficacy of adenoidectomy, or tonsillectomy in children with airway obstruction were included. The weighted mean difference (WMD) and 95% confidence interval (CI) were used for continuous variables. Forest plots were drawn to demonstrate effects in the meta-analyses. RESULTS: Eight papers were included in our study. We found that adenoidectomy and tonsillectomy led to a significant change in nasal-breathing in children with airway obstruction. Children with airway obstruction had a significantly narrower posterior maxillary dental arch than children without airway obstruction (WMD = -0.94, 95% CI [-1.13, -0.76]; P < 0.001). After surgery, these children still had a significantly narrower dental arch than the nasal-breathing children (WMD = -0.60, 95% CI [-0.79, -0.42]; P < 0.001). In terms of dental arch width, malocclusion, palatal height, overjet, overbite, dental arch perimeter, and arch length, a tendency toward normalization was evident following adenoidectomy or tonsillectomy, with no significant differences evident between the surgical group and the normal group. The small number of studies and lack of randomized controlled trials were the main limitations of this meta-analysis. CONCLUSIONS: Following adenoidectomy and tonsillectomy, the malocclusion and narrow arch width of children with airway obstruction could not be completely reversed. Therefore, other treatments such as functional training or orthodontic maxillary widening should be considered after removing the obstruction in the airway. PMID- 27684848 TI - Cross-sectional pupillographic evaluation of relative afferent pupillary defect in age-related macular degeneration. AB - To evaluate, using pupillography, the difference between eyes affected by age related macular degeneration and their contralateral normal eyes with regard to the mean relative afferent pupillary defect (RAPD) score. Also, to ascertain any correlations between this difference in RAPD score and differences in visual acuity or age-related macular degeneration (AMD) dimensions. Measurements were made using the RAPDx pupillographer (Konan Medical, Nishinomiya, Japan), which analyzes pupil response to light stimulation. Both best corrected visual acuity (converted to logMAR) and greatest linear dimension (GLD; calculated on the basis of fluorescence angiography images) were measured. The correlations between RAPD difference and logMAR difference, and GLD difference were then analyzed. The study included 32 patients (18 men, 14 women; mean age = 74.8 +/- 9.7 years) who had AMD in 1 eye and a normal fundus in the contralateral eye. Mean resting pupil diameter, mean latency onset of constriction, mean velocity of constriction, and recovery were not significantly different in AMD eyes compared with normal eyes. The mean amplitude of constriction was smaller (P = 0.028), and the mean latency of maximum constriction was shorter (P = 0.0013) in AMD eyes than in normal eyes. Regarding RAPD scores, there was a significant correlation between visual acuity difference and RAPD score differences of both amplitude (P < 0.001, r = 0.53) and latency (P = 0.034, r = 0.33). GLD difference was also significantly correlated with differences in both amplitude (P = 0.021, r = 0.36) and latency (P = 0.033, r = 0.33) scores. RAPD outcomes were correlated with visual acuity and AMD dimension. Automated pupillography may be a useful tool in monitoring the progression of AMD and assessing changes in retinal function that result from novel interventions. PMID- 27684849 TI - Elastic stable intramedullary nailing for severely displaced distal tibial fractures in children. AB - Elastic stable intramedullary nailing (ESIN) has became a well-accepted method of osteosynthesis of diaphyseal fractures in the skeletally immature patient for many advantages, the purpose of this study is to evaluate the preliminary results of this minimally invasive treatment for severely displaced distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures.This study was carried out over a 6-year period. Twenty-one severely displaced DTDMJ fractures treated using ESIN were evaluated clinically and radiographically. Complications were assessed: the patients were evaluated with regard to nonunion, malunion, infection, growth arrest, leg length discrepancy, implant irritation, and joint function.Mean age at the time of surgery was 7.8 years (range between 5.3 and 14.8 years), mean body weight 34.1 kg, all fractures were transverse or mild oblique type, including 3 open fractures, 5 multifragmented fractures, and 4 fractures associated with polytrauma; 6 cases were treated with antegrade ESIN of tibia while 15 cases need combined retrograde fibula and antegrade tibia fixation treatments. Follow-ups were ranging from 11 to 36 months, 19 fractures showed both clinical and radiographic evidence of healing within 5 months; all cases had full range motion of knee and ankle with symmetrical foot progress angle. Nail removal was at a mean 7.1 months, at final follow-up, no growth arrest or disturbances occurred. Five patients had complications; leg length discrepancy had decreased yet affected 2 patients, 2 cases showed delayed union, and 1 case developed restricted dorsal extension at the metatarsophalangeal joint of the hallux.ESIN is the treatment of choice for pediatric severely displaced DTDMJ fractures that cannot be reduced by closed reduction or ones that cannot be casted. The advantages include faster fracture healing, excellent functional and cosmetic results, safe and reliable surgical technique, and lower severe complication rate. PMID- 27684850 TI - Barbed versus conventional 2-layer continuous running sutures for laparoscopic vaginal cuff closure. AB - We compared results using unidirectional barbed sutures and conventional sutures for vaginal cuff closure during total laparoscopic hysterectomy (TLH).The electronic medical records and surgical videos of 170 patients who underwent TLH between January 2013 and March 2015 at Uijeong-bu St. Mary's Hospital of Catholic University of Korea were reviewed. Vaginal cuffs were closed using the 2-layer continuous running technique with unidirectional barbed sutures (V-Loc; Covidien, Mansfield, MA) in 64 patients and with polycolic acid Vicryl; Ethicon, Somerville, NJ sutures in 106 patients. Procedure time, clinical characteristics, and postoperative complications were compared between the 2 study groups. There were no differences in clinical characteristics (age, body mass index, and demographic data) between groups. The mean suturing time was significantly reduced in the barbed group (7.2 vs 12.2 minutes; P < 0.001), although the mean number of stitches was greater than in the Vicryl group (14.1 vs 12.3, P < 0.001). Perioperative complications, including episodes of vaginal bleeding, vaginal cuff cellulitis, and postoperative fever, did not differ between groups. There were no instances of vaginal cuff dehiscence in either group. Unidirectional barbed sutures can be used safely to reduce procedure time and surgical difficulty relative to conventional sutures in laparoscopic vaginal cuff closure. PMID- 27684851 TI - FDG PET/CT response in diffuse large B-cell lymphoma: Reader variability and association with clinical outcome. AB - F-18-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is essential for monitoring response to treatment in patients with diffuse large B-cell lymphoma (DLBCL) and qualitative interpretation is commonly applied in clinical practice. We aimed to evaluate the interobserver agreements of qualitative PET/CT response in patients with DLBCL and the predictive value of PET/CT results for clinical outcome.PET/CT images were obtained for patients with DLBCL 3 times: at baseline, after 3 cycles of first-line chemotherapy (interim), and after completion of chemotherapy. Two nuclear medicine physicians (with 3 and 8 years of experience with PET/CT) retrospectively assessed response to chemotherapy blinded to the clinical outcome using International Harmonization Project (IHP) criteria and Deauville 5-point score. The associations between PET/CT results and progression-free survival (PFS) and overall survival (OS) were assessed using Cox regression analysis.A total of 112 PET/CT images were included from 59 patients with DLBCL (36 male, 23 female; mean age 53 +/- 14 years). Using the IHP criteria, interobserver agreement was substantial (Cohen kappa = 0.76) with absolute agreement consistency of 89%. Using the Deauville score, interobserver agreement was moderate (Cohen weighted kappa = 0.54) and absolute consistency was 62%. The most common cause of disagreements was discordant interpretation of residual tumor uptake. With median follow-up period of 60 months, estimated 5-year PFS and OS were 81% and 92%, respectively. Neither interim nor posttreatment PET/CT results by both readers were significantly associated with PFS. Interim PET/CT result by the more experienced reader using Deauville score was a significant factor for OS (P = 0.019).Moderate-to substantial interobserver agreement was observed for response assessments according to qualitative PET/CT criteria, and interim PET/CT result could predict OS in patients with DLBCL. Further studies are necessary to further standardize the PET/CT-based response criteria for more consistent interpretation. PMID- 27684852 TI - Preoperative evaluation value of aortic arch lesions by multidetector computed tomography angiography in type A aortic dissection. AB - The purpose of this study was to preoperatively evaluate the value of aortic arch lesions by multidetector computed tomography (MDCT) angiography in type A aortic dissection (AD).From January 2013 to December 2015, we enrolled 42 patients with type A AD who underwent MDCT angiography in our hospital. The institutional database of patients was retrospectively reviewed to identify MDCT angiography examinations for type A AD. Surgical corrections were conducted in all patients to confirm diagnostic accuracy.In this study, the diagnostic accuracy of MDCT angiography was 100% in all 42 patients. The intimal tear site locations that were identified in patients included the ascending aorta (n = 25), aortic arch (n = 12), and all other sites (n = 5). Compared with the control group, there were significant differences in the aortic arch anatomy among the cases. Regarding the distance between the left common carotid and left subclavian arteries, compared with the control group, most cases with type A AD had a significant variation.MDCT angiography plays an important role in detecting aortic arch lesions of type A AD, especially in determining the location of the intimal entry site and change of branch blood vessels. Surgeons can formulate an appropriate operating plan, according to the preoperative MDCT diagnosis information. PMID- 27684854 TI - A nationwide survey of clinical characteristics, management, and outcomes of acute kidney injury (AKI) - patients with and without preexisting chronic kidney disease have different prognoses. AB - Acute kidney injury (AKI) is a common complication in hospitalized patients. The International Society of Nephrology implemented the "0 by 25" initiative aimed at preventing deaths from treatable AKI worldwide by 2025 and conducted a global snapshot survey in 2014. We joined in the project and conducted this study to compare the epidemiology, risk factors, and prognosis between patients with pure AKI and those with acute-on-chronic kidney disease (ACKD). In this study, we prospectively collected demographic parameters and data on clinical characteristics, baseline comorbidities, management, and outcomes of 201 AKI patients in 18 hospitals in Taiwan from September 2014 to November 2014. The in hospital mortality rate was 16%. AKI was mostly attributed to sepsis (52%). Multivariate logistic regression indicated that oliguria was a positive independent predictor of in-hospital mortality, whereas preexisting CKD and exposure to nephrotoxic agents were negative independent predictors. The prevalence of vasopressor use, intensive care unit care, and mortality were significantly higher in pure AKI patients than in ACKD patients. Moreover, serum creatinine (SCr) levels significantly increased within 7 days after AKI diagnosis in nonsurvivors but not in survivors in the pure AKI group. By contrast, SCr levels were persistently lower in nonsurvivors than in survivors in the ACKD group during the same period. We thus determined that the prognosis of ACKD patients differed from that of pure AKI patients. Considering the CKD history in the future AKI staging system may improve prognosis prediction. PMID- 27684855 TI - Estimating the costs of supporting safety-net transformation into patient centered medical homes in post-Katrina New Orleans. AB - There is a need to understand the costs associated with supporting, implementing, and maintaining the system redesign of small and medium-sized safety-net clinics. The authors aimed to understand the characteristics of clinics that transformed into patient-centered medical homes and the incremental cost for transformation.The sample was 74 clinics in Greater New Orleans that received funds from the Primary Care Access and Stabilization Grant program between 2007 and 2010 to support their transformation. The study period was divided into baseline (September 21, 2007-March 21, 2008), transformation (March 22, 2008 March 21, 2009), and maintenance (March 22, 2009-September 20, 2010) periods, and data were collected at 6-month intervals. Baseline characteristics for the clinics that transformed were compared to those that did not. Fixed-effect models were conducted for cost estimation, controlling for baseline differences, using propensity score weights.Half of the 74 primary care clinics achieved transformation by the end of the study period. The clinics that transformed had higher total cost, more clinic visits, and a larger female patient proportion at baseline. The estimated incremental cost for clinics that underwent transformation was $37.61 per visit per 6 months, and overall it cost $24.86 per visit per 6 months in grant funds to support a clinic's transformation.Larger sized clinics and those with a higher female proportion were more likely to transform. The Primary Care Access and Stabilization Grant program provided approximately $24.86 per visit over the 2 and 1/2 years. This estimated incremental cost could be used to guide policy recommendations to support primary care transformation in the United States. PMID- 27684853 TI - Comparison between adrenal venous sampling and computed tomography in the diagnosis of primary aldosteronism and in the guidance of adrenalectomy. AB - In our series of patients with primary aldosteronism, we compared diagnostic concordance and clinical outcomes after adrenalectomy between adrenal venous sampling (AVS) and computed tomography (CT) imaging.Our retrospective analysis included 886 patients with primary aldosteronism diagnosed in our hospital between 2005 and 2014. Of them, 269 patients with CT unilateral adrenal disease were included in the analysis on the diagnostic concordance and 126 patients with follow-up data in the analysis on clinical outcomes after adrenalectomy. Hypertension was considered cured if systolic/diastolic blood pressure (BP) was controlled (<140/90 mm Hg) without medication and improved if BP was controlled with a reduced number of antihypertensive drugs.In 269 patients with CT unilateral adrenal disease, the overall concordance rate between AVS and CT was 50.5% for lateralization on the same side. The concordance rate decreased with increasing age, with highest rate of 61% in patients aged <30 years (n = 16). In 126 patients with follow-up data after adrenalectomy, the AVS- (n = 96) and CT guided patients (n = 30) had similar characteristics before adrenalectomy. After andrenalectomy, the AVS-guided patients had a significantly higher serum potassium concentration (4.3 +/- 0.3 vs 4.0 +/- 0.5 mmol/L, P = 0.04) and rate of cured and improved hypertension (98% vs 87%, P = 0.03). The AVS-guided patients (n = 50) had slightly higher cured rate than the CT-guided patients (n = 11) in those older than 50 years (26.0% vs 18.2%, P = 0.72). The age below which the cured rate in the CT-guided patients was 100% was 30 years.AVS guidance had moderate concordance with CT and slightly improved clinical outcomes after adrenalectomy. The age below which CT unilateralization achieved 100% cured rate was approximately 30 years. PMID- 27684856 TI - Successful treatment of cutaneous squamous cell carcinoma with intralesional cryosurgery: Case report. AB - BACKGROUND: Wide excision or Mohs surgery is the standard treatment of skin squamous cell carcinoma (SCC). Superficial SCC or tumor smaller than 1 cm has been treated successfully with open spray cryosurgery. Larger tumor may not be as effective because tissue destruction is usually superficial. Intralesional cryosurgery (IC) may provide a deeper and better cell killing effect in larger tumors. We investigated the safety and efficacy of treating nodular SCC in 4 patients with IC. METHODS: Four patients with nodular SCC/keratoacanthoma (tumor size, 1-2.5 cm, average 1.48 cm) on the face and extremity were treated with IC. An 18-ga needle was connected to a cryogun and inserted into the center of the tumor after local anesthesia. The tumors were treated with 2 freeze-thaw cycles with a 5- to 10-mm free margin. Additional IC or open spray cryosurgery was applied if residual tumor was noted during monthly follow-up. RESULTS: No patient required analgesics or experienced wound infection after the procedures. After IC, all tumors reduced 40% to 75% in size within 1 week. Two patients received 1 additional spray cryosurgery. Complete remission was noted in all tumors (100%) in 2 months. No recurrence was noted during follow-up (average 5.1 years). All patients were satisfied with the results. CONCLUSION: Our observation suggests that IC can be simple and effective alternative treatment for SCC patients whose condition is not suitable for or who refused operation. PMID- 27684857 TI - The role of radiofrequency ablation for treatment of metachronous isolated hepatic metastasis from colorectal cancer. AB - We investigated recurrence pattern and oncologic outcomes after treatment of metachronous isolated liver metastases from colorectal cancer according to treatment modality.We retrospectively analyzed 123 patients treated with hepatic resection and 82 patients treated with radiofrequency ablation (RFA) for metachronous isolated hepatic metastasis from colorectal cancer (HMCRC). We compared clinicopathological data, recurrence pattern, and recurrence-free survival (RFS) rates after the treatment of hepatic metastasis between patients treated with RFA and resection.The patients in the 2 groups were similar in gender, location of primary tumor, disease-free interval to hepatic metastasis, pathologic stage of primary tumor, and number of hepatic metastasis. The age was older in RFA group but it was not statistically different. The mean diameter of the largest hepatic mass was greater in the resection group than in the RFA group (3.1 vs 1.9 cm, P < 0.001). Chemotherapy after the treatment of hepatic metastasis was more commonly given in hepatic resection group (76.4% vs 62.2%, P = 0.04). Recurrence after the treatment of hepatic metastasis was not significantly different between the 2 groups (54.5% vs 65.9% in the resection and RFA groups). However, intrahepatic recurrence without extra-hepatic metastases was more common in the RFA group than in the resection group (47.5% vs 12.1%, P < 0.001). The RFS rate after the treatment of hepatic metastasis was significantly higher in resection group (48.6% vs 33.7%, P = 0.015). The size and number of hepatic metastasis, primary tumor stage, disease-free interval to hepatic metastasis, and the modality of treatment (RFA vs resection) for hepatic metastasis were confirmed as associated factors with re-recurrence after the treatment of hepatic metastasis. Among patients with solitary hepatic metastases of <=3 cm, marginal recurrence was higher in the RFA group (3% vs 17.2%) and re RFA was performed to achieve comparable recurrence rate (3% vs 5.2%, P = 0.662), the RFS rate was not different between the resection and RFA group (52.4% vs 53.4%, P = 0.491).Surgical resection for HMCRC showed higher RFS. However, the RFS rate in patients with a solitary hepatic metastasis of <=3 cm was similar between the resection and RFA groups. PMID- 27684858 TI - Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis. AB - Serum albumin (S-Alb) is a widely used biomarker of nutritional status and disease severity in patients with autoimmune diseases. We investigated the correlation between S-Alb and the severity of myasthenia gravis (MG).A total number of 166 subjects were recruited in the study. Subjects were divided into 3 groups (T1 to T3) by S-Alb levels: T1: 21.1 to 38.4 g/L, T2: 38.5 to 41.5 g/L, T3: 41.6 to 48.9 g/L. Regression analysis was performed to determine the correlation of initial albumin concentrations and the severity of disease of MG.Lower levels of S-Alb were observed in subjects with increased disease severity than those with slight disease severity, meanwhile, incidence of myasthenia crisis increased in the lower albumin tertiles (P < 0.001). The disease severity assessment was performed according to the criteria established by the Myasthenia Gravis Foundation of America. After adjusting for age, sex, body mass index (BMI), and duration of disease, it showed that higher S-Alb concentrations were associated with lower disease severity. Odds ratios (ORs) of T2 to T3 were 0.241 (95% CI: 0.103-0.566, P < 0.001), 0.140 (95% CI: 0.054-0.367, P < 0.001) when compared with subjects in the T1, respectively. When subjects were stratified into hypoalbuminemia and normal albumin groups, we found that the association between S-Alb and MG remained significant in the hypoalbuminemia group only (OR: 0.693, 95% CI: 0.550-0.874, P = 0.002) after further adjustment for age, sex, BMI, and duration of disease.This is the first study to demonstrate that S-Alb was independently associated with MG severity. In patients with low S Alb, S-Alb concentration could be a potential biomarker for MG disability. PMID- 27684859 TI - Serum fibroblast growth factor 19 is decreased in patients with overt hypothyroidism and subclinical hypothyroidism. AB - As a newly emerging metabolic regulator, accumulating evidence suggests that the circulating fibroblast growth factor 19 (FGF19) level correlated with lipid and glucose metabolism. Several independent groups have found that FGF19 was highly likely associated with multiple metabolic disorders. Thyroid dysfunction is believed to be associated with metabolism diseases. However, to date, few studies have investigated the role of FGF19 in patients with thyroid dysfunctions. For this purpose, a cross-sectional study was done to estimate the role of FGF19 in patients with different thyroid functions. Compared with the healthy control, the present study revealed that serum FGF19 levels were significantly decreased in overt hypothyroidism patients (78.7 [52.7-121.2] vs 292.4 [210.2-426.5] pg/mL, P <0.001). FGF19 concentration was also lower in the subclinical hypothyroidism group than it was in the healthy control group (95.8 [71.7-126.3] vs 292.4 [210.2 426.5] pg/mL, P <0.001). However, there was no significant difference in FGF19 level between the isolated thyroid autoantibody positive group and the healthy control group (252.0 [205.9-353.5] vs 292.4 [210.2-426.5] pg/mL, P >0.05). Also, serum thyroid stimulating hormone (TSH) was an independent predictor of FGF19. In conclusion, thyroid insufficiency but not thyroid autoimmunity may have impacted serum FGF19 concentrations. As the role of FGF19 is becoming more and more important in the pathogenesis of many metabolic diseases, we proposed that the thyroid hormone level should be taken into account when the serum concentration is explained. Further studies are needed to elucidate the role of FGF19 in the development of hypothyroidism. PMID- 27684860 TI - Pedunculated carcinoma ex pleomorphic adenoma of the nasal cavity: A unique case report. AB - BACKGROUND: A carcinoma ex pleomorphic adenoma (CXPA) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma. The parotid gland is the most common location of CXPAs. Minor salivary gland CXPAs of the nasal cavity are exceedingly rare, with only 6 documented in the literature. METHODS AND RESULT: We present a 7th case: an unusual pedunculated intranasal CXPA, which had a favorable outcome after a wide endoscopic excision and the longest follow-up period reported to date. The clinical features, immunohistochemical characteristics, treatment choices, and disease outcomes of the intranasal CXPAs reported in previous studies are also reviewed. CONCLUSION: This case demonstrates the importance of considering the possibility of CXPA in the differential diagnosis of minor salivary gland malignancies in the nasal cavity. PMID- 27684861 TI - Longitudinal association between early atopic dermatitis and subsequent attention deficit or autistic disorder: A population-based case-control study. AB - Atopic dermatitis (AD) is one of the common allergic diseases in children. The presence of allergic diseases was found to have association with the risk of developing attention-deficit hyperactivity disorder (ADHD) or autistic spectrum disorder (ASD) in children, but it is still inconclusive. This study was to investigate the longitudinal relationship between AD developed during toddlerhood and subsequent development of ADHD or ASD in later childhood. Toddlers born between 1998 and 2008 and diagnosed with AD at the age younger than 3 years and older than 1 month were retrieved from Taiwan's National Health Insurance Research Database. Age- and gender-matched toddlers with no lifetime AD were enrolled as the control group. All enrolled toddlers were followed until 2011 to identify the development of ADHD or ASD. Multivariate Cox regression analysis was performed to analyze the hazard ratios (HRs). The risks associated with allergic comorbidities were analyzed. A total of 18,473 toddlers were enrolled into the AD group. The presence of AD significantly increased the risk of developing ADHD (HR = 2.92, 95% confidence interval [CI] = 2.48-3.45) or ASD (HR = 8.90, 95% CI = 4.98-15.92) when aged 3 years or older. Children from the AD group with 3 comorbidities together, namely, allergic rhinitis, allergic conjunctivitis, and asthma, had the greatest risk of developing ADHD and ASD (ADHD: HR = 4.67, 95% CI = 3.81-5.43; ASD: HR = 16.65, 95% CI = 8.63-30.60). In conclusion, toddlers who suffer from AD at the age younger than 3 years are at a higher risk of developing ADHD and ASD during later childhood. Pediatricians taking care of toddlers with AD should have knowledge of this increased risk of developing ADHD and ASD later in life, especially when children have certain comorbidities such as allergic rhinitis, allergic conjunctivitis, and asthma. PMID- 27684862 TI - Comparison of soft tissue balancing, femoral component rotation, and joint line change between the gap balancing and measured resection techniques in primary total knee arthroplasty: A meta-analysis. AB - BACKGROUND: This meta-analysis was designed to compare the accuracy of soft tissue balancing and femoral component rotation as well as change in joint line positions, between the measured resection and gap balancing techniques in primary total knee arthroplasty. METHODS: Studies were included in the meta-analysis if they compared soft tissue balancing and/or radiologic outcomes in patients who underwent total knee arthroplasty with the gap balancing and measured resection techniques. Comparisons included differences in flexion/extension, medial/lateral flexion, and medial/lateral extension gaps (LEGs), femoral component rotation, and change in joint line positions. Finally, 8 studies identified via electronic (MEDLINE, EMBASE, and the Cochrane Library) and manual searches were included. All 8 studies showed a low risk of selection bias and provided detailed demographic data. There was some inherent heterogeneity due to uncontrolled bias, because all included studies were observational comparison studies. RESULTS: The pooled mean difference in gap differences between the gap balancing and measured resection techniques did not differ significantly (-0.09 mm, 95% confidence interval [CI]: -0.40 to +0.21 mm; P = 0.55), except that the medial/LEG difference was 0.58 mm greater for measured resection than gap balancing (95% CI: -1.01 to -0.15 mm; P = 0.008). Conversely, the pooled mean difference in femoral component external rotation (0.77 degrees , 95% CI: 0.18 degrees to 1.35 degrees ; P = 0.01) and joint line change (1.17 mm, 95% CI: 0.82 to 1.52 mm; P < 0.001) were significantly greater for the gap balancing than the measured resection technique. CONCLUSION: The gap balancing and measured resection techniques showed similar soft tissue balancing, except for medial/LEG difference. However, the femoral component was more externally rotated and the joint line was more elevated with gap balancing than measured resection. These differences were minimal (around 1 mm or 1 degrees ) and therefore may have little effect on the biomechanics of the knee joint. This suggests that the gap balancing and measured resection techniques are not mutually exclusive. PMID- 27684863 TI - Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review. AB - Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab.A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb associated aHUS (82,000 AU/mL) without CFHR gene mutations was established.He received Rituximab 375 mg/m (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39).Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion. PMID- 27684864 TI - Minimal change disease in a patient with myasthenia gravis: A case report. AB - BACKGROUND: Myasthenia gravis superimposed with proteinuria is a very rare disorder with only 39 cases reported so far. Of these cases, the most commonly associated disorder is minimal change disease. Myasthenia gravis and minimal change disease are both related to the dysfunction of T lymphocytes and hence the 2 disorders may be connected. METHODS: Here we report the first case on a patient diagnosed with myasthenia gravis concurrently with the minimal change disease, and it was presented in the absence of thymoma or thymic hyperplasia. RESULTS: Treatment for myasthenia gravis also lowered proteinuria of minimal change disease. He ever experienced good control for myasthenia gravis and minimal change disease. However, pneumonia related septic shock occurred to him and finally he was dead. Minimal change disease is generally considered to occur subsequent to the onset of myasthenia gravis with causal association. After extensive literature review, we noted only 47.8% minimal change disease had occurred after the onset of myasthenia gravis. CONCLUSION: Minimal change disease mostly occurs in children and if diagnosed in adults, clinicians should search for a potential cause such as myasthenia gravis and other associated thymic disorders. PMID- 27684865 TI - Injury of the dorsolateral prefronto-thalamic tract in a patient with depression following mild traumatic brain injury: A case report. AB - BACKGROUND: Depression, a prevalent psychiatric disorder, is associated with abnormality in the prefrontal cortex, particularly the left dorsolateral prefrontal cortex. In this study, we report on a patient with severe depression who showed injury of the dorsolateral prefronto-thalamic tract following mild traumatic brain injury, which was demonstrated by diffusion tensor tractography (DTT). METHODS AND RESULTS: A 63-year-old female patient suffered an in-car accident. The patient lost consciousness for approximately 10 minutes and experienced posttraumatic amnesia approximately 30 minutes from the time of the accident. Her Glasgow Coma Scale score was 15. No specific lesion was observed on the conventional brain magnetic resonance imaging. Since the onset of head trauma, she had shown continuous depression and on 32 month evaluation, she exhibited severe depression (Beck Depression Inventory-II: 42 [full score: 63 score] and Patient Health Questionnaire-9: 24 [full score: 27 score]). RESULTS: On 32-month DTT, partical tearing of the dorsolateral prefronto-thalamic tract was observed in the right hemisphere and thinning in the left hemisphere. CONCLUSION: Injury of the dorsolateral prefronto-thalamic tract was demonstrated in a patient with depression following mild traumatic brain injury, using DTT. We believe that injury of the dorsolateral prefronto-thalamic tract might be a pathogenetic mechanism of depression in patients with brain injury. PMID- 27684866 TI - Transsacrococcygeal approach to ganglion impar block for treatment of chronic coccygodynia after spinal arachnoid cyst removal: A case report. AB - BACKGROUND: Coccygodynia is a pain in the region of the coccyx that radiates to the sacral, perineal area. The cause of the pain is often unknown. Coccygodynia is diagnosed through the patient's past history, a physical examination, and dynamic radiographic study, but the injection of local anesthetics or a diagnostic nerve blockade are needed to distinguish between somatic, neuropathic, and combined pain. Ganglion impar is a single retroperitoneal structure made of both paravertebral sympathetic ganglions. Although there are no standard guidelines for the treatment of coccygodynia, ganglion impar blockade is one of the effective options for treatment. METHODS: Here, we report a 42-year-old female patient presenting with severe pain in the coccygeal area after spinal arachnoid cyst removal. RESULTS: Treatment involved neurolysis with absolute alcohol on the ganglion impar through the transsacrococcygeal junction. Pain was relieved without any complications. CONCLUSION: Our case report offers the ganglion impar blockade using the transsacrococcygeal approach with absolute alcohol can improve intractable coccydynia. PMID- 27684867 TI - Spontaneously removed biliary stent drainage versus T-tube drainage after laparoscopic common bile duct exploration. AB - Several studies have shown the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) as a minimally invasive treatment options for choledocholithiasis. Use of T-tube or biliary stent drainage tube placement after laparoscopic choledochotomy for common bile duct (CBD) stones is still under debate. This study tried to confirm the safety of spontaneously removable biliary stent in the distal CBD after LCBDE to allow choledochus primary closure. A total of 47 patients with choledocholithiasis underwent LCBDE with primary closure and internal drainage using a spontaneously removable biliary stent drainage tube (stent group, N = 22) or T-tube (T-tube group, N = 25). Operative parameters and outcomes are compared. Surgical time, intraoperative blood loss, length of hospital stay, drainage tube removal time, postoperative intestinal function recovery, and cost of treatment were all significantly lower in the stent group as compared to that in the T-tube group (P < 0.05 for all). Otherwise, Bile leakage between the two groups had no significant difference (P > 0.05). The biliary stent drainage tube was excreted spontaneously 4 to 14 days after surgery with the exception of one case, where endoscopic removal of biliary tube was required due to failure of its spontaneous discharge. LCBDE with primary closure and use of spontaneously removable biliary stent drainage showed advantage over the use of traditional T-tube drainage in patients with choledocholithiasis. PMID- 27684868 TI - Long-term remission after low dose radiotherapy in patient with extensive squamous cell carcinoma of the hand: A case report. AB - RATIONALE FOR CASE REPORT: Cutaneous Squamous Cell Carcinoma (cSCC) of the hand is uncommon and tends to have poorer outcomes. Surgical resection with wide margins around the tumor is recommended as the treatment of choice, and radiotherapy is considered second-line treatment. Nodal evaluation involves dissection necessitating some morbidity. The role of less invasive modalities of nodal evaluation is not well established. CASE PRESENTATION: We report a case of locally advanced case of hand cSCC. Positron emission tomography-computed tomography (PET-CT) showed disease involving full thickness of the hand as well as the ipsilateral axillary node. To achieve adequate surgical margins would have necessitated amputation at the wrist, which the patient did not consent to. Instead, he was given a two-and-a-half week course radiotherapy to the hand without axillary radiation. With the radiotherapy treatment, he managed to achieve complete remission of disease while retaining full function of the hand, which was maintained at 22 months post-treatment. MAIN LESSONS: CSCC of the hand is uncommon and challenging to treat. Radiotherapy is a highly effective treatment modality which is able to achieve functional preservation. Care should be taken when evaluating nodal status using PET-CT. PMID- 27684869 TI - Hemopericardium caused by a mobile retained epicardial pacing wire after ventricular septal defect repair: A case report. AB - BACKGROUND: Epicardial pacing wires (EPWs) are commonly employed for diagnosis and treatment of arrhythmia in the acute phase after cardiac surgery. Although rare, retained EPWs may cause mild-to-catastrophic complications. The present case demonstrates hemopericardium caused by a mobile retained EPW. METHODS: A 49 year-old woman presented to our emergency department with clinical signs of impending cardiac tamponade. She had undergone ventricular septal defect repair 7 years before this admission. An initial computed tomography (CT) scan revealed hemopericardium with suspicion of a possible intracardiac lesion. Review of the first and second CT scans, however, revealed a mobile retained EPW penetrating the pericardium in the first scan, which had moved out of the pericardium in the second scan. RESULTS: Because cardiac injury by the EPW was suspected, the patient was transferred to another medical center for further treatment. CONCLUSION: According to our experience with this case, diagnosis may be incorrect if CT is unable to obtain decisive images of the mobile EPW at the correct time. Multiplanar reconstruction and volume rendering can increase diagnostic accuracy. In conclusion, if hemopericardium is present without clear etiology in a patient with a retained EPW, a nearby mobile EPW may be the cause. PMID- 27684870 TI - Coreceptor usage of Chinese HIV-1 and impact of X4/DM transmission clusters among recently infected men who have sex with men. AB - To characterize the current frequency of HIV-1 coreceptor usage in China and assess the candidacy of CCR5 antagonists for treatment of HIV infections. In addition, we aimed to evaluate the potential of X4/DM virus transmission in recently infected men who have sex with men (MSM) individuals.Viral tropism testing was performed on samples from 399 MSM individuals and on 2408 available Chinese HIV-1 V3 sequences downloaded from the Los Alamos database using Geno2pheno and WebPSSM in combination. The transmission clusters were evaluated using pol sequences from 291 recently infected MSM with a maximum likelihood, maximum pairwise distance, and Bayesian inference.A higher prevalence of X4/DM viruses was observed in individuals infected with CRF01_AE strains than with subtype B (27.8% vs 12.2%, P < 0.001) and CRF07_BC/CRF08_BC/C (27.8% vs 1.0%, P < 0.001). Seven clusters containing only X4/DM viruses were detected in 40 transmission clusters. No significant difference in proportions between clustered X4/DM viruses and R5 viruses was found (P = 0.683).The high proportion of CXCR4 usage for CRF01_AE strains may result in the loss of susceptibility to maraviroc since CRF01_AE has become the most prevalent strains in China. The high prevalence of X4/DM viruses among recently CRF01_AE-infected individuals may be attributed to the stochasticity of HIV transmission, which implied that the early viral tropism screening and treatment would be the key for controlling the epidemic of CRF01_AE strains in China. PMID- 27684871 TI - Efficacy of ultrasound-guided fascia iliaca compartment block after hip hemiarthroplasty: A prospective, randomized trial. AB - BACKGROUND: The fascia iliaca compartment block (FICB) provides an analgesic effect in patients with femur fractures. However, the postoperative pain after hip surgery is different from that after femur fracture, because of the difference in the degree and location of tissue trauma. Whether FICB provides effective postoperative analgesia in patients undergoing total hip arthroplasty is not well understood. Moreover, there is no prospective randomized study to evaluate FICB as a postoperative analgesia in hemiarthroplasty. Therefore, we performed a randomized and prospective study to determine the effect of FICB after hemiarthroplasty. The objective of this study was to compare the opioid consumption between patients who received intravenous patient-controlled analgesia (PCA) with and without FICB. METHODS: Twenty-two patients aged 70 to 90 years who underwent bipolar hemiarthroplasty for femoral neck fracture were recruited and allocated randomly into 2 groups: FICB group (n = 11) and Non-FICB group (n = 11). All patients received spinal anesthesia with 10 mg of 0.5% hyperbaric bupivacaine. After surgery, the FICB was conducted using a modified technique with 0.2% ropivacaine (40 mL) under ultrasonographic guidance, and the intravenous PCA was administered to patients in both groups in the separate block room. The PCA was set up in the only bolus mode with no continuous infusion. The visual analog scale (VAS) and the opioid consumption were noted at 4, 8, 12, 24, and 48 hours postoperatively. RESULTS: The VAS was similar in both groups. The fentanyl requirement at 4, 8, and 12 hours was low in the FICB group. The total amount of fentanyl required in the first 24 hours was 246.3 MUg in the FICB group and 351.4 MUg in the Non-FICB group. No patient developed any residual sensory motor deficit during the postoperative period. Patients in the Non-FICB group had nausea (n = 2), and pruritus (n = 1), and 1 patient had nausea in the FICB group during postoperative 2 days. CONCLUSION: The FICB has a significant opioid sparing effect in first 24 hours after hemiarthroplasty. This suggests that FICB is an effective way for multimodal analgesia in hip surgery. PMID- 27684873 TI - Risk factors for "late-to-test" HIV diagnosis in Riverside County, California. AB - Patients diagnosed late in the course of HIV infection are at an increased risk of negative health outcomes and are more likely to transmit HIV to others. Using the CDC's definition for AIDS, we analyzed case report data from persons diagnosed with AIDS within 12 months of an HIV diagnosis ("late-to-test") in Riverside County, CA, between 2009 and 2014. Of 1385 HIV cases, 422 (30.5%) were late-to-test. Factors associated with late-to-test were: having no insurance (P = 0.005), being Hispanic (P = 0.002) and being between 45 and 64 years of age (P < 0.001). Females (P = 0.013) and those in the eastern region of Riverside County (P = 0.002) were less likely to be late-to-test. In the absence of universal HIV testing, interventions to decrease late testing are needed. PMID- 27684872 TI - Increased Enterococcus faecalis infection is associated with clinically active Crohn disease. AB - This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID- 27684874 TI - Predictive factors for anti-HBs status after 1 booster dose of hepatitis B vaccine. AB - In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (?10 mIU/mL) or protective postbooster anti-HBs status (?100 mIU/mL).We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (?10 mIU/mL, model 1) and protective postbooster anti-HBs status (?100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex.Twenty-four students got positive postbooster anti HBs status (10-100 mIU/mL) and 50 students got protective postbooster anti-HBs status (?100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (?10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (?100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence interval between 1.552 and 2.959, and the P value was less than 0.001.Prebooster anti-HBs level can be the powerful predictive factor for positive postbooster anti-HBs status (?10 mIU/mL) and protective postbooster anti-HBs status (?100 mIU/mL). According to the result of this study, if someone received complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels around 2 decades later, 1 booster dose of HBV vaccine could help him or her to regain positive postbooster anti-HBs status (?10 mIU/mL) under the strong predictive factor of prebooster anti-HBs level higher than 1 mIU/mL. The other 2 HBV vaccines could be saved and the case could also save money and time. PMID- 27684876 TI - EIF2AK4 mutation in pulmonary veno-occlusive disease: A case report and review of the literature. AB - BACKGROUND: Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of pulmonary arterial hypertension with a non-specific clinical presentation and a relatively specific presentation in high-resolution thoracic CT scan images. Definitive diagnosis is made by histological examination in previous. According to the 2015 ESC/ERS Guidelines, detection of a mutation in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) without histological confirmation is recommended to validate the diagnosis of PVOD. METHODS: We report the case of a 27-year-old man who was admitted for persistent cough and dyspnea that had lasted for 5 months and had developed and experienced progressive dyspnea for the last 2 months. The echocardiogram and right heart catheterization without vasodilator challenge confirmed the diagnosis of pulmonary arterial hypertension. Other tests, such as high-resolution thoracic CT scan, V/Q scan, pulmonary function test with diffusion capacity, and blood tests, excluded other associated diseases which could have caused pulmonary hypertension. RESULTS: The initial diagnosis at admission was idiopathic pulmonary arterial hypertension and an oral vasodilator (sildenafil) was given. However, the dyspnea subsequently worsened, and the patient was transferred to a regional lung transplant center, where he died of heart failure 1 week later. Using exome sequencing, we found an EIF2AK4 mutation, which was sufficient to confirm the diagnosis of PVOD. CONCLUSION: This is the first reported case of EIF2AK4 mutation in PVOD in a Chinese patient population. We found the frameshift EIF2AK4 mutation c.1392delT (p.Arg465fs) in this case. Up to now, there has been a paucity of data on this rare disease, and the exact role of EIF2AK4 loss-of function mutations in the pathogenesis of PVOD is still unknown. More investigations should be conducted in the future. PMID- 27684875 TI - Risk factors for early mortality after hepatectomy for hepatocellular carcinoma. AB - Despite advances in surgical technique and medical care, liver resection for hepatocellular carcinoma (HCC) remains a high-risk major operation. The present study evaluated the risk factors for early mortality after hepatectomy.We retrospectively reviewed records of patients undergoing liver resection for HCC between 1983 and 2015. A point score (Risk Assessment for early Mortality (RAM) score) for hepatectomy was developed based on multivariate analyses.Three hundred eighty-three patients (11.3%) expired within 6 months after the operation. Logistic regression analyses identified that operative duration >270 minutes and blood loss >800 cc were significant predictors of major surgical complications (P = 0.013 and 0.002, respectively). On the other hand, diabetes mellitus, albumin <=3.5 g/dL, alpha-fetoprotein (AFP) >200 ng/mL, major surgical procedure, blood loss >800 cc, and major surgical complications were independent risk factors for early mortality after hepatectomy (P = 0.019, <0.001, <0.001, 0.006, 0.018, and <0.001, respectively). Risk Assessment for early Mortality score (RAM score) identified 3 subgroups of patients with distinct 6-month mortality rate, with Class III (score 10) having highest risk of early mortality.Our study demonstrated that meticulous surgical techniques to minimize blood loss and avoid prolonged operative time may help decrease the occurrence of major surgical complications. In addition to major surgical complications, diabetes mellitus, hypoalbuminemia, high AFP, massive blood loss, and major surgical procedure are also associated with early mortality after liver resection. Further study is warranted to validate the utility of RAM score as a bedside scoring system to predict postoperative outcome. PMID- 27684877 TI - Prevalence and risk factors of sepsis-induced cardiomyopathy: A retrospective cohort study. AB - The aim of the study is to evaluate the epidemiology and clinical features of sepsis-induced cardiomyopathy (SICM).A retrospective cohort study was conducted.A total of 210 adult patients with sepsis or septic shock admitted to a Japanese tertiary care hospital from January 1, 2013, to December 31, 2015, who underwent transthoracic echocardiography (TTE) on admission.The definition of SICM was ejection fraction (EF) < 50% and a >=10% decrease compared to the baseline EF which recovered within 2 weeks, in sepsis or septic shock patients.Our primary outcome was the incidence rate of SICM. Our secondary outcomes were the in hospital mortality rate and length of intensive care unit (ICU) stay according to the presence or absence of SICM. In total, 29 patients (13.8%) were diagnosed with SICM. The prevalence rate of SICM was significantly higher in male than in female (P = 0.02). Multivariate logistic regression analyses revealed that the incidence of SICM was associated with younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95-0.99), higher lactate level on admission (OR, 1.18; 95% CI, 1.05-1.32) and history of heart failure (HF) (OR, 3.77; 95% CI, 1.37-10.40). There were no significant differences in the in-hospital and 30-day mortality between patients with and without SICM (24.1% vs 12.7%, P = 0.15; 20.7% vs 12.1%, P = 0.23). Lengths of hospital and ICU stay were significantly longer in patients with SICM than in those without SICM (median, 43 vs 26 days, P = 0.04; 9 vs 5 days, P < 0.01).SICM developed in 13.8% of patients with sepsis and septic shock. A younger age, higher lactate levels on admission and history of HF were risk factors. PMID- 27684879 TI - Laminoplasty with lateral mass screw fixation for cervical spondylotic myelopathy in patients with athetoid cerebral palsy: A retrospective study. AB - Although several studies report various treatment solutions for cervical spondylotic myelopathy in patients with athetoid cerebral palsy, long-term follow up studies are very rare. None of the reported treatment solutions represent a gold standard for this disease owing to the small number of cases and lack of long-term follow-up. This study aimed to evaluate the outcomes of laminoplasty with lateral mass screw fixation to treat cervical spondylotic myelopathy in patients with athetoid cerebral palsy from a single center.This retrospective study included 15 patients (9 male patients and 6 female patients) with athetoid cerebral palsy who underwent laminoplasty with lateral mass screw fixation for cervical spondylotic myelopathy at our hospital between March 2006 and June 2010. Demographic variables, radiographic parameters, and pre- and postoperative clinical outcomes determined by the modified Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and visual analog scale (VAS) scores were assessed.The mean follow-up time was 80.5 months. Developmental cervical spinal canal stenosis (P = 0.02) and cervical lordosis (P = 0.04) were significantly correlated with lower preoperative modified JOA scores. The mean modified JOA scores increased from 7.97 preoperatively to 12.1 postoperatively (P < 0.01). The mean VAS score decreased from 5.30 to 3.13 (P < 0.01), and the mean NDI score decreased from 31.73 to 19.93 (P < 0.01). There was a significant negative correlation between developmental cervical spinal canal stenosis and recovery rate of the modified JOA score (P = 0.01).Developmental cervical spinal canal stenosis is significantly related to neurological function in patients with athetoid cerebral palsy. Laminoplasty with lateral mass screw fixation is an effective treatment for cervical spondylotic myelopathy in patients with athetoid cerebral palsy and developmental cervical spinal canal stenosis. PMID- 27684878 TI - Effect of sex differences in remifentanil requirements for the insertion of a laryngeal mask airway during propofol anesthesia: A prospective randomized trial. AB - BACKGROUND: Remifentanil can improve insertion of a laryngeal mask airway (LMA) during induction with propofol. Recently, it has been suggested that there is a sex difference in opioid requirements for this procedure. The purposes of this study were to determine the effective effect-site concentration (Ce) of remifentanil for the facilitation of LMA insertion in male and female patients during propofol anesthesia without neuromuscular blockade and to evaluate whether there are sex differences in the Ce of remifentanil required for successful LMA insertion. METHODS: Forty-eight patients (24 male, 24 female) with American Society of Anesthesiologists physical status 1 or 2, aged 20 to 60 years, scheduled for minor orthopedic surgery under general anesthesia were enrolled. Anesthesia was induced by target-controlled infusion (TCI) of propofol and remifentanil. The target Ce of propofol was 5 MUg/mL initially and was reduced to 3.5 MUg/mL after loss of consciousness. The Ce of remifentanil given to each patient was determined by the response of the previously tested patient using 0.5 ng/mL as a step size. The 1st patient was tested at a Ce of 3.0 ng/mL of remifentanil. Successful LMA insertion was defined as smooth insertion without patient movement or significant resistance to mouth opening. RESULTS: The effective Ce of remifentanil required for successful LMA insertion on 50% of occasions (effective effect-site concentration for 50% [EC50]) as estimated by Dixon method was significantly lower in women (2.18 +/- 0.35 ng/mL) than in men (2.82 +/- 0.53 ng/mL) (P = 0.02). Using the isotonic regression method, the effective Ce of remifentanil required for successful LMA insertion on 95% of occasions (EC95) (95% confidence interval [CI]) was significantly lower in women (3.38 [3.0-3.48] ng/mL) than in men (3.94 [3.80-3.98] ng/mL). CONCLUSION: The Ce of remifentanil required to facilitate successful LMA insertion is higher during propofol induction by TCI in men than in women. When using remifentanil for LMA insertion, patient sex should be taken into account for appropriate dosing. PMID- 27684880 TI - Interleukin-8 gene polymorphism -251T>A contributes to Alzheimer's disease susceptibility. AB - BACKGROUND: Published association studies have investigated the correlation between interleukin-8 (IL-8) gene polymorphism -251T>A and susceptibility to Alzheimer's disease (AD); however, the results are conflicting. Thus, we conducted the meta-analysis to reassess the effect of IL-8 gene -251T>A variant on the risk of AD. METHODS: Relevant studies regarding this association were electronically searched and identified from the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. The odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs) were pooled to calculate the strength of this association. RESULTS: Nine studies with a total of 1406 cases and 2152 controls were included in the meta-analysis. Overall, a significant association of IL-8 gene -251T>A polymorphism with increased risk of AD was observed in several genetic models (allele, A vs T: OR=1.32, 95%CI=1.16-1.50; homozygous, AA vs TT: OR=1.70, 95%CI=1.21-2.21; heterozygous, TA vs TT: OR=1.37, 95%CI=1.12-1.69; recessive, AA vs TA+TT: OR=1.40, 95%CI=1.12-1.75). Similarly, such association was also revealed both in Asian and European populations in the subgroup analysis by ethnicity. CONCLUSION: The current study suggested that IL-8 gene polymorphism -251T>A may contribute to the susceptibility to AD. PMID- 27684881 TI - Lymph nodes metastasis of gastric cancer: Measurement with multidetector CT oblique multiplanar reformation-correlation with histopathologic results. AB - The aim of this study was to retrospectively evaluate the ability of multidetector computed tomography (MDCT) oblique multiplanar reformation (MPR) for differentiating metastatic lymph nodes (LNs) in patients with gastric cancer.Seventy-nine patients with gastric cancer underwent preoperative computed tomography (CT). One-to-one correlation of LN was made between CT oblique multiplanar reformation and histopathologic slides. Long diameters, short diameters, and short-to-long axis ratios of LNs were evaluated to differentiate metastasis.Short diameters of nodes performed better for diagnosing metastasis than long diameters and short-to-long ratios. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve of short diameter were 57.8%, 74.7%, 68.2%, and 0.713, respectively. With different thresholds of short diameters of nodes (No. 8 group >6 mm and other groups >4 mm), total sensitivity, specificity, and accuracy can reach 57.2%, 79.0%, and 70.3%, respectively.MDCT oblique MPR images have certain reference value to distinguish metastasis of LNs in gastric cancer. The diagnostic power for LN metastasis of gastric cancer can be improved by using different threshold for No. 8 group LNs and other groups. PMID- 27684882 TI - Crohn's disease mistaken for long-standing idiopathic mesenteric panniculitis: A case report and management algorithm. AB - BACKGROUND: Mesenteric panniculitis (MP) is mostly an associated sign of an intra abdominal or systemic inflammatory primary disease. Nevertheless, etiological and differential diagnosis of idiopathic MP can be challenging when an associate primary cause is not in the foreground. METHODS: We report here the case of an isolated small bowel Crohn's disease, long time considered as idiopathic MP. RESULTS: This patient presented to our department with a 10-year history of acute abdominal symptoms evolving with flare-up and remission. A diagnosis of idiopathic MP was made based on compatible CT-scan features along with normal laboratory tests and upper and lower bowel endoscopies. As symptoms recurred, a steroid course was proposed which dramatically improved his condition for years. Finally, an explorative laparoscopy was performed because of concern of malignancy when he returned to our unit with a steroid refractory flare-up and weight loss, along with MP nodes growing up to 10 mm. Crohn's disease was eventually diagnosed, based on histopathological middle-gut bowel resection and numerous granulomas in mesenteric nodes without necrosis. CONCLUSION: This case emphasizes the importance of excluding inflammatory intestinal lesions before making the diagnosis of idiopathic MP (fecal calprotectin, magnetic resonance enterography, wireless capsule endoscopy). PMID- 27684883 TI - Competitive Transplants to Evaluate Hematopoietic Stem Cell Fitness. AB - The gold standard definition of a hematopoietic stem cell (HSC) is a cell that when transferred into an irradiated recipient will have the ability to reestablish blood cell production for the lifespan of the recipient. This protocol explains how to set up a functional assay to compare the HSC capacities of two different populations of cells, such as bone marrow from mice of two different genotypes, and how to analyze the recipient mice by flow cytometry. The protocol uses HSC equivalents rather than cell sorting for standardization and discusses the advantages and disadvantages of both approaches. We further discuss different variations to the basic protocol, including serial transplants, limiting dilution assays, homing assays and non-competitive transplants, including the advantages and preferred uses of these varied approaches. These assays are central for the study of HSC function and could be used not only for the investigation of fundamental HSC intrinsic aspects of biology but also for the development of preclinical assays for bone marrow transplant and HSC expansion in culture. PMID- 27684884 TI - Synchronous Low-grade Appendiceal Mucinous Neoplasm and Primary Peritoneal Low grade Serous Carcinoma: A First Description of These 2 Neoplasms Presenting Together as Suspected Peritoneal Carcinomatosis. AB - Low-grade appendiceal mucinous neoplasm is a neoplasm typically of appendiceal origin, which is characterized by diffuse peritoneal involvement by pools of mucin with mucinous epithelium lacking high-grade cytologic atypia, and clinically presents as suspected peritoneal carcinomatosis. A similar clinical presentation can sometimes be seen with disseminated low-grade serous carcinomas of the peritoneum, fallopian tubes, or ovaries; however, this neoplasm is histologically characterized by tubal-type epithelium and invasive or confluent growth. In this case report, we describe a patient presenting with a clinical examination and radiologic features suggestive of peritoneal carcinomatosis and a prominent pelvic mass; however, after pathologic review, the patient was proven to have peritoneal involvement by both low-grade appendiceal mucinous neoplasm of appendiceal origin and a low-grade peritoneal primary serous carcinoma. In short, we present the first description of low-grade appendiceal mucinous neoplasm and serous carcinoma of the peritoneum presenting synchronously, providing morphologic characterization and immunohistochemical studies supporting the diagnosis, and illustrating a rare instance in which 2 neoplastic processes are underlying clinically suspected peritoneal carcinomatosis. PMID- 27684885 TI - Primary Ovarian Malignant PEComa: A Case Report. AB - Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm characterized by expression of both melanocytic and smooth muscle markers. PEComas are rarely encountered in the female genital tract. We report a case of malignant primary PEComa of the ovary, and discuss the differential diagnosis. This represents the first case of primary typical malignant PEComa of the ovary. PMID- 27684886 TI - Local Mosquito-Borne Transmission of Zika Virus - Miami-Dade and Broward Counties, Florida, June-August 2016. AB - During the first 6 months of 2016, large outbreaks of Zika virus disease caused by local mosquito-borne transmission occurred in Puerto Rico and other U.S. territories, but local mosquito-borne transmission was not identified in the continental United States (1,2). As of July 22, 2016, the Florida Department of Health had identified 321 Zika virus disease cases among Florida residents and visitors, all occurring in either travelers from other countries or territories with ongoing Zika virus transmission or sexual contacts of recent travelers.* During standard case investigation of persons with compatible illness and laboratory evidence of recent Zika virus infection (i.e., a specimen positive by real-time reverse transcription-polymerase chain reaction [rRT-PCR], or positive Zika immunoglobulin M [IgM] with supporting dengue serology [negative for dengue IgM antibodies and positive for dengue IgG antibodies], or confirmation of Zika virus neutralizing antibodies by plaque reduction neutralization testing [PRNT]) (3), four persons were identified in Broward and Miami-Dade counties whose infections were attributed to likely local mosquito-borne transmission. Two of these persons worked within 120 meters (131 yards) of each other but had no other epidemiologic connections, suggesting the possibility of a local community-based outbreak. Further epidemiologic and laboratory investigations of the worksites and surrounding neighborhood identified a total of 29 persons with laboratory evidence of recent Zika virus infection and likely exposure during late June to early August, most within an approximate 6-block area. In response to limited impact on the population of Aedes aegypti mosquito vectors from initial ground based mosquito control efforts, aerial ultralow volume spraying with the organophosphate insecticide naled was applied over a 10 square-mile area beginning in early August and alternated with aerial larviciding with Bacillus thuringiensis subspecies israelensis (Bti), a group biologic control agent, in a central 2 square-mile area. No additional cases were identified after implementation of this mosquito control strategy. No increases in emergency department (ED) patient visits associated with aerial spraying were reported, including visits for asthma, reactive airway disease, wheezing, shortness of breath, nausea, vomiting, or diarrhea. Local and state health departments serving communities where Ae. aegypti, the primary vector of Zika virus, is found should continue to actively monitor for local transmission of the virus.(?). PMID- 27684887 TI - Highlights in Gastrointestinal (Colorectal) Cancer Treatment: The Primary Tumor Sidedness Debate and Advances in Immunotherapy. PMID- 27684888 TI - A Zero-Dimensional Model and Protocol for Simulating Patient-Specific Pulmonary Hemodynamics From Limited Clinical Data. AB - In pulmonary hypertension (PH) diagnosis and management, many useful functional markers have been proposed that are unfeasible for clinical implementation. For example, assessing right ventricular (RV) contractile response to a gradual increase in pulmonary arterial (PA) impedance requires simultaneously recording RV pressure and volume, and under different afterload/preload conditions. In addition to clinical applications, many research projects are hampered by limited retrospective clinical data and could greatly benefit from simulations that extrapolate unavailable hemodynamics. The objective of this study was to develop and validate a 0D computational model, along with a numerical implementation protocol, of the RV-PA axis. Model results are qualitatively compared with published clinical data and quantitatively validated against right heart catheterization (RHC) for 115 pediatric PH patients. The RV-PA circuit is represented using a general elastance function for the RV and a three-element Windkessel initial value problem for the PA. The circuit mathematically sits between two reservoirs of constant pressure, which represent the right and left atriums. We compared Pmax, Pmin, mPAP, cardiac output (CO), and stroke volume (SV) between the model and RHC. The model predicted between 96% and 98% of the variability in pressure and 98-99% in volumetric characteristics (CO and SV). However, Bland Altman plots showed the model to have a consistent bias for most pressure and volumetric parameters, and differences between model and RHC to have considerable error. Future studies will address this issue and compare specific waveforms, but these initial results are extremely promising as preliminary proof of concept of the modeling approach. PMID- 27684889 TI - Implementation of the Four-Category Classification of Cesarean Section Urgency in Clinical Practice. A Prospective Study. AB - PURPOSE: This study is aimed at investigating the clinical efficacy of the 4 category classification of urgent cesarean section. METHODS: Women giving birth from September 2012 to December 2014 were prospectively investigated. Urgency C section categories were color-coded: red - maternal/fetal life threat; yellow - maternal/fetal compromise, not life-threatening; and green - early delivery necessary. Results were audited. RESULTS: A total of 4,754 women gave birth in the period considered, 1,313 (27.6%) with C-section of which 867 were urgent. The code was red in 0.98% of women, and 91.5% of newborns were delivered <=30'; yellow in 5.1%; and green in 11.7%. The mean decision-to-delivery interval (DDI) +/- SD was 19.6 +/- 9.5 min, 36.6 +/- 15.3 (p < 0.01), and 80.3 +/- 52.8 (p < 0.01), respectively; and mean umbilical pH was 7.24 +/- 0.10, 7.29 +/- 0.08 (p < 0.05), and 7.33 +/- 0.04 (p < 0.01) in the red, yellow, and green groups, respectively. Two (4.2%) red and 4 (2.2%) yellow newborns were acidotic. Mean DDI +/- SD decreased from 21.7 +/- 9.7 min in the period September 2012 to February 2013 to 17.4 +/- 9.7 min in the period February to December 2014 (p = NS). CONCLUSIONS: Four-category classification led to achieving the target time in >90% of category 1 emergency C-sections, and stratified newborns with significantly different acidosis levels. PMID- 27684891 TI - Effects of Functional Training and Calf Stretching on Risk of Falls in Older People: A Pilot Study. AB - This study aimed to determine the effects of a functional training and ankle stretching program in triceps surae torque, passive stiffness index, and in the risk for fall indicators in older adults. Twenty women (73.4 +/- 7.3 years) were allocated into an intervention or control group. The 12-week intervention consisted of functional training and calf stretching exercises performed twice a week. Measurements of peak passive and active torque, passive stiffness, maximum dorsiflexion angle, and indexes of risk for falls (Timed Up and Go, functional reach test, QuickScreen-test) were collected. There were no significant differences for all variables, except the maximum dorsiflexion angle, which increased in the intervention group from 33.78 +/- 8.57 degrees to 38.89 +/- 7.52 degrees . The exercise program was not sufficient to enhance performance on functional tests and decrease the risk for falls in older adults. The significant increase in the maximum dorsiflexion indicates a positive impact of stretching exercises. PMID- 27684890 TI - Involvement of the caudate nucleus head and its networks in sporadic amyotrophic lateral sclerosis-frontotemporal dementia continuum. AB - We investigated common structural and network changes across the sporadic amyotrophic lateral sclerosis (ALS)-frontotemporal dementia (FTD) continuum. Based on cluster analysis using the frontotemporal assessment battery, 51 patients with sporadic ALS were subdivided into three groups: 25 patients with ALS with cognitive deficiency (ALS-CD); seven patients who satisfied FTD criteria (ALS-FTD), and 19 patients with ALS with normal cognitive function (ALS-NC). Compared with the controls, gray matter images from patients with ALS-FTD showed atrophic changes in the following order of severity: caudate head, medial frontal gyrus, thalamus, amygdala, putamen, and cingulate gyrus (peak level, uncorrected p < 0.001). The caudate head was significant at the cluster level using FWE correction (p < 0.05). Diffusion tensor imaging with tract-based spatial statistics revealed white matter changes in the areas surrounding the caudate head, the internal capsule, and the anterior horn of the lateral ventricle in the ALS-CD and ALS-FTD. Probabilistic diffusion tractography showed a significant decrease in structural connectivity between the caudate head and the dorsomedial frontal cortex and the lateral orbitofrontal cortex, even in the ALS-NC. Our results indicated that the caudate head and its networks were the most vulnerable to lesion in sporadic ALS-FTD-spectrum patients associated with cognitive decline with FTD features. PMID- 27684892 TI - Activities of daily living in people with lower limb amputation: outcomes of an intervention to reduce dependence in pre-prosthetic phase. AB - PURPOSE: The main objective was to assess the change in the functional independence in basic activities of daily living (ADL) following a pre-prosthetic intervention in people with lower-limb amputation (LLA). Secondary objectives were to identify the factors contributing to the success of this intervention, and to analyze the effects on the presence of unmet needs for home adaptation. METHOD: The ADL intervention was early and pre-prosthetic; it was focused on six self-care activities. Fifty-two adults with LLA, who required assistance in self care, were included. Functional independence (Barthel) was assessed at baseline and after intervention (T2). Successful intervention was defined as independent performance of all self-care activities. RESULTS: There was a significant improvement in Barthel scores between baseline and T2 in toileting (p < 0.001), bed-chair transfers (p < 0.001), dressing (p < 0.001), bathing/showering (p < 0.001), and feeding (p = 0.025). The proportion of homes with an unmet need for adaptation decreased significantly in bathroom (p = 0.008) and other internal areas (p = 0.031). Intervention was successful for 61.5% of participants. In a multivariate model, age was significantly associated with successful intervention (OR 0.66, 95%CI 0.52-0.83). CONCLUSIONS: A short and pre-prosthetic ADL intervention improves functional independence and reduces the need for home adaptation. ADL programs should be included in rehabilitation strategies. Implications for Rehabilitation Because basic activities of daily living (ADL) can be seriously compromised after a lower-limb amputation, it is important for this population to improve or maintain their level of independence. A short and pre-prosthetic ADL intervention is an effective method for an early recovery of functional independence in self-care activities and promotes home adaptation. Age is an important determinant of functional recovery, and most subjects can achieve independence in basic ADL regardless of the level of amputation. A pre-prosthetic ADL program should be included in rehabilitation strategies for adults with lower limb amputation. PMID- 27684894 TI - Targeted expression of HvHMA2 increases the mineral content of the inner endosperm in barley. AB - Cereals are a major source of dietary energy and protein but are nutritionally poor in micronutrients. Zinc (Zn) biofortification of staple crops has been proposed as a promising strategy to combat the global challenge of human Zn deficiency. The aim of this study was to improve the Zn content in the edible part of the barley (Hordeum vulgare L.) grain by enhancing Zn translocation into the developing seeds. We demonstrate that the barley plasma membrane P-type ATPase Zn transporter, HvHMA2 is an efficient candidate for mineral biofortification of crops. Following a cisgenic approach to produce transgenic homozygous barley line over-expressing HvHMA2 in the transfer cells of the grain, resulted in a doubling of a wide range of nutrients including Zn, iron (Fe), and magnesium (Mg) in the inner endosperm. This article is protected by copyright. All rights reserved. PMID- 27684893 TI - Pathogenic Escherichia coli and enteric viruses in biosolids and related top soil improvers in Italy. AB - AIMS: To investigate the presence of genomic traits associated with a set of enteric viruses as well as pathogenic Escherichia coli in top soil improvers (TSI) from Italy. METHODS AND RESULTS: Twenty-four TSI samples originating from municipal sewage sludges, pig manure, green and household wastes were analysed by real time PCR for the presence of hepatitis E virus (HEV), porcine and human adenovirus (HuAdV), norovirus, rotavirus and diarrhoeagenic E. coli. None of the samples was found positive for HEV or rotavirus. Four samples were positive for the presence of nucleic acids from human norovirus, two of them being also positive for HuAdV. Real time PCR screening gave positive results for many of the virulence genes characteristic of diarrhoeagenic E. coli in 21 samples. These included the verocytotoxin-coding genes, in some cases associated with intimin coding gene, and markers of enteroaggregative, enterotoxigenic and enteroinvasive E. coli. CONCLUSIONS: These results provide evidence that enteric viruses and pathogenic E. coli may be released into the environment through the use of sludge derived TSI. SIGNIFICANCE AND IMPACT OF THE STUDY: The results highlight that the TSI-related environmental risk for the food chain should be more deeply assessed. PMID- 27684896 TI - Editorial. AB - There is a new and healthy drive in the NHS to ensure that research underpins all activity. The health secretary put his stamp of approval on the research priority last week when he delivered the opening address at a scientific health conference. Stephen Dorrell declared that research should be undertaken and implemented to improve patient care. Mr Dorrell wants an 'effectiveness index' readily available to practitioners to ensure the best research underpins clinical care and treatment. And while the health department has invested in research and development and is pushing evidence based practice, it does appear that research is not research in the government's eyes if the findings are contrary to its policies. In the week that Mr Dorrell preached about evidence based practice, the health department itself was found wanting in disseminating a research report which was politically embarrassing. PMID- 27684895 TI - Scleroderma overlap syndromes. PMID- 27684897 TI - Report endorses patient-focused care. AB - Nurses working in patient- focused care hospitals fear they will be given low status tasks unwanted by other professionals, a government commissioned report has found. PMID- 27684898 TI - Twelve hour shifts bad for patient care. AB - Patient care suffers when nurses are made to switch from eight hour to 12 hour shifts, a new study has shown. PMID- 27684899 TI - Purchasers uncertain of practice nurses' role. AB - Practice nurses see their wide range of work as a strength, while health authorities and trusts can view it as a problem, the Scientific Basis of Health Services conference heard. PMID- 27684900 TI - Ex-patient returns to train at hospital. AB - A woman is to train to be a nurse at the hospital which saved her life. PMID- 27684901 TI - Back injury nurse wins case. AB - A district nurse who won L50,000 compensation for a back injury has encouraged fellow nurses to pursue claims. PMID- 27684904 TI - ? AB - An image from pressure group Baby Milk Action's 1996 calendar, published last week. Copies available from Baby Milk Action, 23 St Andrew's Street, Cambridge CB2 3AX. PMID- 27684902 TI - Bar codes used on ward tasks. AB - Researchers brought supermarket technology on to the wards to help nurses assess the best way to use their time, last week's Scientific Basis of Health Services conference heard. PMID- 27684905 TI - Tender delay sparks fears for Scottish nurse teachers' jobs. AB - Nurse teachers in Scotland are facing an uncertain future I because the Scottish Office has delayed an announcement about I who will run their colleges. PMID- 27684908 TI - Every hospital will be linked to information superhighway. AB - Labour leader Tony Blair has promised to link the entire National Health Service to the information superhighway. PMID- 27684907 TI - Doomed hospital has soaring sickness rate. AB - Nurse sickness rates at a doomed north London hospital have soared, sparking fears for patient safety, an RCN officer claimed last week. PMID- 27684909 TI - Labour will scrap gagging clauses in NHS contracts. AB - Labour has pledged to fight moves to turn the NHS into a second-rate 'safety net' service for the poor. PMID- 27684911 TI - Private firms' contracts will be honoured. AB - Calls for a Labour government to cancel contracts which allow private firms to run NHS hospitals have been resisted by the party's health team. PMID- 27684910 TI - Talk to midwives as well as GPs says RCM. AB - Labour health planners have been urged to pay less attention to doctors and more to midwives when developing maternity service policies. PMID- 27684912 TI - Professor says research must provide evidence for changes. AB - The survival of nursing will depend on a coherent research strategy in which innovation is preceded by evidence to support change, the audience at the annual Winifred Raphael Memorial Lecture was told. PMID- 27684913 TI - Swedish nurses are likely to strike in support of pay claim. AB - Swedish nurses have threatened to go on strike if their bosses fail to offer them a pay rise of at least 11 per cent this year. PMID- 27684914 TI - Economics course leads to ward sisters' efficiency project. AB - Nurses in Sweden are helping their health service save thousands of pounds and making the healthcare system more efficient, according to a report in a Swedish newspaper. PMID- 27684916 TI - Cholesterol predicts CHD risk in women. AB - The association between high total cholesterol and mortality from coronary heart disease is comparable in men and women, according to a major research study from The Netherlands. PMID- 27684915 TI - RCN announces new Council members for 1995 to 1999. AB - The Royal College of Nursing has announced the new line up of its ruling Council following the election of members for 1995 to 1999. PMID- 27684917 TI - Vitamin A for common cause of blindness? AB - Large doses of vitamin A might help prevent age related macular degeneration (ARMD) and blindness, American researchers think. PMID- 27684918 TI - HCV carriers and risk of spread to family. AB - Preventive measures against the spread of hepatitis C (HCV) might not be necessary in close contacts of symptomless carriers, researchers from Rome report. PMID- 27684919 TI - Scarring reduced by new gel formula. AB - A gel developed by a Manchester researcher holds out the promise of reduced scarring. PMID- 27684920 TI - Capital calls. AB - Where would you go to hire an elephant? No, this is not the first line of a corny joke but a genuine enquiry to Capital Radio's helpline. The London radio station has been fielding such questions, and rather more serious ones, since 1994, as a service to its listeners. PMID- 27684921 TI - Football stars a welcome sight for health promotion. AB - How refreshing to see a photograph of the much maligned, but also adulated, Eric Cantona on the news pages (October 4). PMID- 27684923 TI - Bags of urine don't have to be on display. AB - Thank you for your excellent CE article on care of urinary catheters, (Nursing Standard September 27) but I must point out a glaring omission from the text. Nowhere did it say 'In order to preserve patient privacy and dignity if at all possible either conceal the bag under bedclothes, or at the very least hang it opaque side out'. PMID- 27684922 TI - Mental illness bias must be stopped. AB - I would like to say how true and interesting I found Mike Lehane's article 'Mental illness can damage your career', I (Viewpoint September 27). PMID- 27684924 TI - One Minute Wisdom. AB - For many years waiting lists have been top of the politicians' agenda. Often we hear political parties quoting waiting lists statistics to either indicate good or poor management of the National Health Service. PMID- 27684925 TI - Clinical reference amendment. AB - In the article 'A critical appraisal of preceptorship' (Nursing Standard. 1995. 9, 45, 25-28), the author cited reference number 23 incorrectly. The correct reference should read: Kershaw B. Clinical credibility and nurse teachers. Nursing Standard. 1990.4, 51,46-47. PMID- 27684926 TI - One rule for them, another for nurses. AB - The article 'employers resist a national pay deal' (News September 27) states that Ipswich Hospital has awarded nurses 3 per cent. PMID- 27684927 TI - Will nurses fork out for PREP training? AB - I see a survey by the MSF and Leeds University says women are more likely to pay for their own training (News October 4). PMID- 27684928 TI - Sensible footwear can avoid litigation. AB - In response to the letter 'Some parts of the uniform don't fit' (Letters September 12) the writer states she hates wearing duty shoes and tights and feels the hierarchy makes her wear them for insurance purposes. PMID- 27684929 TI - Information exchange. PMID- 27684931 TI - Listings. PMID- 27684930 TI - protecting the patient or just playing politics? AB - Our experts consider a hot topic of the day. PMID- 27684932 TI - Body posture and gender impact neural processing of power-related words. AB - Judging others' power facilitates successful social interaction. Both gender and body posture have been shown to influence judgments of another's power. However, little is known about how these two cues interact when they conflict or how they influence early processing. The present study investigated this question during very early processing of power-related words using event-related potentials (ERPs). Participants viewed images of women and men in dominant and submissive postures that were quickly followed by dominant or submissive words. Gender and posture both modulated neural responses in the N2 latency range to dominant words, but for submissive words they had little impact. Thus, in the context of dual-processing theories of person perception, information extracted from both behavior (i.e., posture) and from category membership (i.e., gender) are recruited side-by-side to impact word processing. PMID- 27684933 TI - Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO. AB - BACKGROUND: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from urinary incontinence and decreased sexual health after surgery. MATERIAL AND METHODS: We prospectively collected data from a non-selected group of men undergoing radical prostatectomy in 14 centers between 2008 and 2011. Before surgery, we asked about preparedness for surgery-induced urinary problems and decreased sexual health. One year after surgery, we asked about bother caused by urinary incontinence and erectile dysfunction. As a measure of the association between preparedness and bothersomeness we modeled odds ratios (ORs) by means of logistic regression. RESULTS: Altogether 1372 men had urinary incontinence one year after surgery as well as had no urinary leakage or a small urinary dribble before surgery. Among these men, low preparedness was associated with bother resulting from urinary incontinence [OR 2.84; 95% confidence interval (CI) 1.59 5.10]. In a separate analysis of 1657 men we found a strong association between preparedness for decreased sexual health and experiencing bother from erectile dysfunction (OR 5.92; 95% CI 3.32-10.55). CONCLUSION: In this large-sized prospective trial, we found that preparedness before surgery for urinary problems or sexual side effects decreases bother from urinary incontinence and erectile dysfunction one year after surgery. PMID- 27684936 TI - Correction: Efficient Removal of Co2+ from Aqueous Solution by 3 Aminopropyltriethoxysilane Functionalized Montmorillonite with Enhanced Adsorption Capacity. AB - [This corrects the article DOI: 10.1371/journal.pone.0159802.]. PMID- 27684935 TI - An Elderly Woman with Tongue Ischemia. PMID- 27684934 TI - Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases. AB - Uracil-DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil-DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis. Within this family the enzymes of poxviruses are unique and most remarkable in terms of amino acid sequences, characteristic motifs and more importantly for their novel non-enzymatic function in DNA replication. UNG of vaccinia virus, also known as D4, is the most extensively characterized UNG of the poxvirus family. D4 forms an unusual heterodimeric processivity factor by attaching to a poxvirus-specific protein A20, which also binds to the DNA polymerase E9 and recruits other proteins necessary for replication. D4 is thus integrated in the DNA polymerase complex, and its DNA-binding and DNA scanning abilities couple DNA processivity and DNA base excision repair at the replication fork. The adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three-dimensional structure of D4. An overview of the current state of the knowledge on the structure-function relationship of D4 is provided here. PMID- 27684937 TI - Image analysis of neutrophil nuclear morphology: Learning about phenotypic range and its reliable analysis from patients with pelger-Huet-anomaly and treated with colchicine. AB - The nuclear morphology of neutrophils depends on different endogenous and exogenous factors, which can lead to hypo- or hypersegmentation of the normally 2 4 segmented nucleus. Hyposegmentation can be due to mutations in the LBR-gene (Pelger-Huet-Anomaly) or can be induced, for example, by colchicine treatment. The range of this phenotypic variation is known as "norm of reaction," which can be of major relevance for clinical diagnosis and therapeutic intervention. In this project, we studied the norm of reaction in 26 subjects with 0-3 wild type LBR alleles. In addition, the phenotypic variation was analyzed in 3 patients with Familial Mediterranean Fever (FMF), before and after colchicine treatment. We measured the phenotype nuclear segmentation of neutrophils based on two conventional qualitative methods, the "rule of threads" and the "rule of thirds." In addition, we tested a morphometric quantitative approach, the "circularity index." The circularity index was superior in cases with hyposegmentation; the rule of thirds with respect to hypersegmentation. Approximately 65% of the observed phenotypic variance was explainable by the number of LBR wild type alleles. The gene-dosage effect followed a non-additive, hysteresis-like characteristic with lower and upper plateaus. Colchicine treatment had a clear, although minor phenotypic effect compared to the number of LBR wild type genes or the mutation type. Thus, the nuclear morphology of granulocytes and its norm of reaction can be regarded as an excellent model both for detailing the interplay between endogenous and exogenous factors and for clinical diagnostic purposes. (c) 2016 International Clinical Cytometry Society. PMID- 27684939 TI - 'We go to the bush to prove that we are also men': traditional circumcision and masculinity in the accounts of men who have sex with men in township communities in South Africa. AB - In predominantly isiXhosa-speaking township communities in South Africa, men who have sex with men negotiate their identities and sexual practices alongside heteronormative cultural scripts of what it means to be a man. Such idealised notions of masculinity are predicated on the selective appropriation of cultural practices that preserve (heterosexual) male privilege and power. In this paper, we explore the identity work done by men who have sex with men, with particular reference to male circumcision as a cultural practice widely drawn on to inform and regulate normative masculinity. Through a narrative-discursive analysis of the accounts provided by men who have sex with men from township communities, we highlight how participants' dissident sexualities are constructed as compromising their masculine identities. Participating in cultural practices such as traditional circumcision aligns participants to the idealised forms of masculinity that afford men full citizenship in their communities. Study findings suggest that sexual dissidence is less troubling to participants than deviating from gendered markers of hegemonic masculinity, and point to ways in which marginalised men might have an interest in maintaining the dominant gendered order. We conclude with implications for research and programmatic work with gay, bisexual and other men who have sex with men. PMID- 27684938 TI - CD147 and Prostate Cancer: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Prostate cancer is one of the most common non-cutaneous malignancies in men. We aimed to systemically evaluate the relationship between the expression of CD147 in tissues and the clinicopathological features of prostate cancer. METHODS AND FINDINGS: PubMed (1966-2016), EMBASE (1980-2016), the Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and the WanFang databases (1988-2016) were searched. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Meta analysis was performed by using Review Manager 5.3 and Stata 13.0. A total of 12591 prostate cancer patients from 14 studies were included. The results of the meta-analysis showed that there were significant differences in the positive expression rate in the following comparisons: prostatic cancer tissues vs. normal prostate tissues (odds ratio [OR] = 26.93, 95% confidence interval [CI] 7.95 91.20, P < 0.00001), prostatic cancer tissues vs. benign prostatic hyperplasia tissues (OR = 20.54, 95% CI 8.20-51.44, P < 0.00001), high Gleason score vs. low Gleason score (OR = 2.39, 95% CI 1.33-4.27, P = 0.03), TNM III to IV vs. TNM I to II (OR = 9.95, 95% CI 4.96-19.96, P < 0.00001), low or moderate differentiation vs. high differentiation (OR = 8.12, 95% CI 3.69-17.85, P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 4.31, 95% CI 1.11-16.71, P = 0.03), and distant metastasis vs. non-distant metastasis (OR = 8.90, 95% CI 3.24 24.42, P < 0.00001). CONCLUSION: The CD147 positive expression rate was closely related to the clinical characteristics of prostate cancer, but more research is needed to confirm the findings owing to the results of the subgroups. PMID- 27684941 TI - Two poles of the Th 17-cell-mediated disease spectrum: Analysis of a case series of 21 patients with concomitant lupus erythematosus and psoriasis. PMID- 27684940 TI - Gene Polymorphisms of FABP2, ADIPOQ and ANP and Risk of Hypertriglyceridemia and Metabolic Syndrome in Afro-Caribbeans. AB - OBJECTIVES: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities and cardiovascular risk factors that are highly heritable and polygenic. We investigated the association of allelic variants of three candidate genes, rs1799883-FABP2, rs1501299-ADIPOQ and rs5065-ANP with MetS and its components, individually and in combination, using a genetic risk score. METHODS: A cross sectional study was conducted in 462 Afro-Caribbeans subjects without cardiovascular complications or lipid-lowering medications. Cardiovascular risk factors and MetS components (NCEP-ATPIII criteria) were recorded. The 3 SNPs were genotyped. The genetic risk score was calculated by summing the number of risk alleles at each locus. Logistic regressions were used. RESULTS: Fifty-eight participants (12.6%) were diabetics and 116 (25.1%) had a MetS. In a dominant model, rs1799883 was associated with hypertriglyceridemia (OR 2.22; P = 0.014) and hypertriglyceridemic waist (HTGW), (P = 0.014) but not significantly with overweight (P = 0.049), abdominal obesity (P = 0.033) and MetS (P = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (P = 0.028) and 2.19 (P = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (P = 0.075). The genetic risk score was significantly associated with MetS. Subjects carrying 4-5 risk alleles (18.8%) had a nearly 2.5-fold-increased risk of MetS compared to those carrying 0-1 risk allele (24.3%): OR 2.31; P = 0.025. CONCLUSIONS: This study supports the association of FABP2, ANP and ADIPOQ gene variants with MetS or its components in Afro-Caribbeans and suggests a cumulative genetic influence of theses variants on this syndrome and a potential effect on lipid metabolism. PMID- 27684942 TI - Drosophila Adaptation to Viral Infection through Defensive Symbiont Evolution. AB - Microbial symbionts can modulate host interactions with biotic and abiotic factors. Such interactions may affect the evolutionary trajectories of both host and symbiont. Wolbachia protects Drosophila melanogaster against several viral infections and the strength of the protection varies between variants of this endosymbiont. Since Wolbachia is maternally transmitted, its fitness depends on the fitness of its host. Therefore, Wolbachia populations may be under selection when Drosophila is subjected to viral infection. Here we show that in D. melanogaster populations selected for increased survival upon infection with Drosophila C virus there is a strong selection coefficient for specific Wolbachia variants, leading to their fixation. Flies carrying these selected Wolbachia variants have higher survival and fertility upon viral infection when compared to flies with the other variants. These findings demonstrate how the interaction of a host with pathogens shapes the genetic composition of symbiont populations. Furthermore, host adaptation can result from the evolution of its symbionts, with host and symbiont functioning as a single evolutionary unit. PMID- 27684943 TI - The Efficacy of Natalizumab versus Fingolimod for Patients with Relapsing Remitting Multiple Sclerosis: A Systematic Review, Indirect Evidence from Randomized Placebo-Controlled Trials and Meta-Analysis of Observational Head-to Head Trials. AB - BACKGROUND: Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). METHODS AND FINDINGS: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect = 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). CONCLUSIONS: Indirect analyses of RCT data and head-to head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation. PMID- 27684944 TI - PB2-Q591K Mutation Determines the Pathogenicity of Avian H9N2 Influenza Viruses for Mammalian Species. AB - BACKGROUND: Influenza A subtype H9N2 is widespread and prevalent in poultry. It has repeatedly transmitted zoonotically to cause mild influenza-like illness in humans and is regarded as a potential pandemic candidate. In additon, the six internal genes of H7N9 and H10N8 viruses which caused infection in human in China as well as some of the highly pathogenic H5N1 strains are origined from H9N2. Previous studies have shown that the mammalian adaptation PB2-Q591K contributes to the pathogenicity of H5N1 and H7N9 viruses. However, the role of the PB2-Q591K mutation in H9N2 subtype is still not well understood. METHODS: To define and compare the individual role of PB2-Q591K substitution in the PB2 gene segment of H9N2 in relation to polymerase activity, replication competence and the pathogenicity using in vitro and in vivo models. RESULTS: The PB2-Q591K mutation in H9N2 virus enhanced the polymerase activity and virus replication in human NHBE cells when compared to the wild type strain. Mice infected with the PB2 mutant showed significant weight loss, higher virus replication and immune responses in the lungs. CONCLUSIONS: Our evidences suggest that the PB2-Q591K, in addition to the -E627K mutation in H9N2 enhanced the pathogenicity in mammalian host. PMID- 27684945 TI - Oral administration of antioxidants improves skin wound healing in diabetic mice. AB - Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b+ and Ly6G+ cells) and reduced levels of KC, TNF-alpha, IL-1beta, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG+ /CD206- macrophages whereas CD206+ /MIG- macrophages were decreased. Cytokines IL-12p40, TNF-alpha, IL-1beta, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia. PMID- 27684947 TI - Interactions of Aqueous Imidazolium-Based Ionic Liquid Mixtures with Solid Supported Phospholipid Vesicles. AB - Despite the environmentally friendly reputation of ionic liquids (ILs), their safety has been recently questioned given their potential as cytotoxic agents. The fundamental mechanisms underlying the interactions between ILs and cells are less studied and by far not completely understood. Biomimetic films are here important biophysical model systems to elucidate fundamental aspects and mechanisms relevant for a large range of biological interaction ranging from signaling to drug reception or toxicity. Here we use dissipative quartz crystal microbalance QCM-D to examine the effect of aqueous imidazolium-based ionic liquid mixtures on solid-supported biomimetic membranes. Specifically, we assess in real time the effect of the cation chain length and the anion nature on a supported vesicle layer of the model phospholipid DMPC. Results indicate that interactions are mainly driven by the hydrophobic components of the IL, which significantly distort the layer and promote vesicle rupture. Our analyses evidence the gradual decrease of the main phase transition temperature upon increasing IL concentration, reflecting increased disorder by weakening of lipid chain interactions. The degree of rupture is significant for ILs with long hydrophobic cation chains and large hydrophobic anions whose behavior is reminiscent of that of antimicrobial peptides. PMID- 27684948 TI - Past, present, and future of neuropsychology in Argentina. AB - OBJECTIVE: To describe the history, current situation, and future challenges of Argentinian neuropsychology. METHOD: A brief historical description highlighting the most representative authors and publications is made. In addition, a survey was administered to a sample of 135 neuropsychologists practicing neuropsychology in Argentina. The survey explored the current neuropsychological practices among the respondents. RESULTS: Results show that most Argentinian neuropsychologists are: psychologists, women, and work in the clinical field in the country's major cities. Besides, the practice of neuropsychology is mostly unregulated with few training opportunities. CONCLUSIONS: Argentinian neuropsychology emerged from neurology in the early twentieth century and slowly progressed until the 1960s when the first organized research groups were created. Since then, a substantial and steady progress followed. However, more training opportunities and a better regulation of the discipline are needed. No similar studies have been conducted in the past, thus becoming one of the first to describe the development of neuropsychology in Argentina. PMID- 27684950 TI - Letter to the Editor to the article: The Effects of a Transition to Minimalist Shoe Running on Intrinsic Foot Muscle Size. PMID- 27684946 TI - Maternal obesity and neurodevelopmental and psychiatric disorders in offspring. AB - There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. (c) 2016 John Wiley & Sons, Ltd. PMID- 27684949 TI - Development and Application of the Remote Food Photography Method to Measure Food Intake in Exclusively Milk Fed Infants: A Laboratory-Based Study. AB - BACKGROUND: Accurate methods of assessing food intake in infants are needed to assess the relationship between infant feeding practices and risk of childhood obesity. Current methods are either subjective or have limited ability for use beyond clinical research settings. OBJECTIVE: To assess the accuracy of the RFPM to evaluate simulated milk intake including energy, macronutrient, and micronutrient intake compared to direct weighing within a controlled study. METHODS: Individuals were recruited to prepare three 2 fl oz, 4 fl oz, 6 fl oz, and 8 fl oz servings of infant formula and to capture photographs at different stages of preparation (dry powdered formula, prepared formula, and liquid waste) using the SmartIntake(r) application. Gram weights of the bottles were obtained by the RFPM and direct weighing. Using the United States Department of Agriculture National Nutrient Database for Standard Reference, energy, macronutrient, and micronutrient values were generated from gram weights. RESULTS: Intake of formula prepared from powder measured by the RFPM was equivalent to weighed intake within 7.5% equivalence bounds among all servings and each serving size. The mean difference between methods varied among servings sizes with the RFPM underestimating intake by 1.6 +/- 0.4 kcals in 2 fl oz servings, 4.8 +/- 0.6 kcals in 4 fl oz servings, and 6.2 +/- 1.0 kcals in 6 fl oz servings, and overestimating intake by 0.1 +/- 1.2 kcals in 8 fl oz servings. Bland-Altman analysis showed that the RFPM overestimated intake at lower levels food intake and underestimated intake at higher levels. Considering photographs of only the prepared formula bottle and the bottle with formula waste to simulate ready-to-feed formula and human breast milk, intake estimated by the RFPM was equivalent to the directly weighed intake within 7.5% for all servings. CONCLUSIONS: The RFPM has higher accuracy than subjective methods and similar accuracy as compared to the objective methods in estimating simulated intake of milk and formula with lower burden to caregivers. The RFPM is a viable method for measuring intake in exclusively milk fed infants by caregivers in a controlled environment with potential for widespread use in research and clinical practice. PMID- 27684951 TI - Response to the Letter to the Editor for article: The Effects of a Transition to Minimalist Shoe Running on Intrinsic Foot Muscle Size. PMID- 27684952 TI - A Step by Step Protocol for Subretinal Surgery in Rabbits. AB - Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in adults in industrially developed countries. RPE transplantation appears to be a promising therapy, as it may replace dysfunctional RPE, restore its function, and thereby vision. Here we describe a method for transplanting a cultured RPE monolayer on a scaffold into the subretinal space (SRS) of rabbits. After vitrectomy xenotransplants were delivered into the SRS using a custom made shooter consisting of a 20-gauge metallic nozzle with a polytetrafluoroethylene (PTFE) coated plunger. The current technique evolved in over 150 rabbit surgeries over 6 years. Post-operative follow-up can be obtained using non-invasive and repetitive in vivo imaging such as spectral domain optical coherence tomography (SD-OCT) followed by perfusion-fixed histology. The method has well-defined steps for easy learning and high success rate. Rabbits are considered a large eye animal model useful in preclinical studies for clinical translation. In this context rabbits are a cost-efficient and perhaps convenient alternative to other large eye animal models. PMID- 27684954 TI - Appropriate use of inhaled corticosteroids in COPD: the candidates for safe withdrawal. AB - International guidance on chronic obstructive pulmonary disease (COPD) management recommends the use of inhaled corticosteroids (ICS) in those patients at increased likelihood of exacerbation. In spite of this guidance, ICS are prescribed in a large number of patients who are unlikely to benefit. Given the evidence of the risks associated with ICS and the limited indications for their use, there is interest in understanding the effects of withdrawing ICS when prescribed inappropriately. In this review, we discuss the findings of large ICS withdrawal trials, with primary focus on the more recent trials using active comparators. Data from these trials indicate that ICS may be withdrawn without adverse impact on exacerbation risk and patient-reported outcomes in patients with moderate COPD and no history of frequent exacerbations. Considering the safety concerns associated with ICS use, these medications should be withdrawn in patients for whom they are not recommended, while maintaining adequate bronchodilator therapy. PMID- 27684955 TI - G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay. AB - Forster resonance energy transfer (FRET)-based studies have become increasingly common in the investigation of GPCR signaling. Our research group developed an intra-molecular FRET sensor to detect the interaction between Galpha subunits and GPCRs in live cells following agonist stimulation. Here, we detail the protocol for detecting changes in FRET between the beta2-adrenergic receptor and the Galphas C-terminus peptide upon treatment with 100 uM isoproterenol hydrochloride as previously characterized(1). Our FRET sensor is a single polypeptide consisting serially of a full-length GPCR, a FRET acceptor fluorophore (mCitrine), an ER/K SPASM (systematic protein affinity strength modulation) linker, a FRET donor fluorophore (mCerulean), and a Galpha C-terminal peptide. This protocol will detail cell preparation, transfection conditions, equipment setup, assay execution, and data analysis. This experimental design detects small changes in FRET indicative of protein-protein interactions, and can also be used to compare the strength of interaction across ligands and GPCR-G protein pairings. To enhance the signal-to-noise in our measurements, this protocol requires heightened precision in all steps, and is presented here to enable reproducible execution. PMID- 27684953 TI - Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells. AB - Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer. PMID- 27684956 TI - The SNARC Effect in Chinese Numerals: Do Visual Properties of Characters and Hand Signs Influence Number Processing? AB - The SNARC effect refers to an association of numbers and spatial properties of responses that is commonly thought to be amodal and independent of stimulus notation. We tested for a horizontal SNARC effect using Arabic digits, simple form Chinese characters and Chinese hand signs in participants from Mainland China. We found a horizontal SNARC effect in all notations. This is the first time that a horizontal SNARC effect has been demonstrated in Chinese characters and Chinese hand signs. We tested for the SNARC effect in two experiments (parity judgement and magnitude judgement). The parity judgement task yielded clear, consistent SNARC effects in all notations, whereas results were more mixed in magnitude judgement. Both Chinese characters and Chinese hand signs are represented non-symbolically for low numbers and symbolically for higher numbers, allowing us to contrast within the same notation the effects of heavily learned non-symbolic vs. symbolic representation on the processing of numbers. In addition to finding a horizontal SNARC effect, we also found a robust numerical distance effect in all notations. This is particularly interesting as it persisted when participants reported using purely visual features to solve the task, thereby suggesting that numbers were processed semantically even when the task could be solved without the semantic information. PMID- 27684957 TI - beta-Catenin Accumulation Is Associated With Increased Expression of Nanog Protein and Predicts Maintenance of MSC Self-Renewal. AB - Human mesenchymal stem cells (hMSCs) are self-renewing cells with the ability to differentiate into organized, functional network of cells. Recent studies have revealed that activation of the Wnt/beta-catenin pathway by a glycogen synthase kinase (GSK)-3-specific pharmacological inhibitor, Bio, results in the maintenance of self-renewal in both mouse and human ES cells. The molecular mechanism behind the maintenance of hMSCs by these factors, however, is not fully understood. We found that rEGF enhances the level of beta-catenin, a component of the Wnt/beta-catenin signaling pathway. Furthermore, it was found that beta catenin upregulates Nanog. EGF activates the beta-catenin pathway via the Ras protein and also increased the Nanog protein and gene expression levels 2 h after rEGF treatment. These results suggest that adding EGF can enhance beta-catenin and Nanog expression in MSCs and facilitate EGF-mediated maintenance of MSC self renewal. EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population and thus did not induce differentiation. Thus, EGF not only can be used to expand MSC in vitro but also be utilized to autologous transplantation of MSCs in vivo. PMID- 27684959 TI - Erythromelalgia in patients with essential thrombocythemia and polycythemia vera. PMID- 27684958 TI - MetaPhinder-Identifying Bacteriophage Sequences in Metagenomic Data Sets. AB - Bacteriophages are the most abundant biological entity on the planet, but at the same time do not account for much of the genetic material isolated from most environments due to their small genome sizes. They also show great genetic diversity and mosaic genomes making it challenging to analyze and understand them. Here we present MetaPhinder, a method to identify assembled genomic fragments (i.e.contigs) of phage origin in metagenomic data sets. The method is based on a comparison to a database of whole genome bacteriophage sequences, integrating hits to multiple genomes to accomodate for the mosaic genome structure of many bacteriophages. The method is demonstrated to out-perform both BLAST methods based on single hits and methods based on k-mer comparisons. MetaPhinder is available as a web service at the Center for Genomic Epidemiology https://cge.cbs.dtu.dk/services/MetaPhinder/, while the source code can be downloaded from https://bitbucket.org/genomicepidemiology/metaphinder or https://github.com/vanessajurtz/MetaPhinder. PMID- 27684960 TI - Effect of platelet-rich plasma on degeneration change of rotator cuff muscles: In vitro and in vivo evaluations. AB - Atrophy with fatty degeneration is often seen in rotator cuff muscles with torn tendons. PRP has been reported to enhance tissue repair processes after tendon ruptures. However, the effect of PRP on atrophy and fatty degeneration of the muscle is not yet known. The aim of this study is to examine the effect of PRP on degeneration change of rotator cuff muscles in vitro and in vivo. A murine myogenic cell line and a rat rotator cuff tear model were used in this study and PRP was administrated into subacromial space which is widely used in clinical practice. In in vitro study, administration of PRP to C2C12 cells stimulated cell proliferation while inhibited both myogenic and adipogenic differentiation. In in vivo study, administration of PRP suppressed Oil Red-O positive lipid droplet formation. The expression of adipogenic genes was also decreased by PRP administration. In conclusion, PRP promoted proliferation of myoblast cells, while inhibiting adipogenic differentiation of myoblast cells and suppressing fatty degeneration change in rat torn rotator cuff muscles. Further investigations are needed to determine the clinical applicability of the PRP. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1806-1815, 2017. PMID- 27684961 TI - Association of the IKZF1 5' UTR variant rs1456896 with lupus nephritis in a northern Han Chinese population. AB - OBJECTIVES: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. METHOD: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls. Replication was conducted in an independent cohort comprising 798 LN patients and 704 healthy controls. Using the ENCODE (Encyclopedia of DNA Elements) databases, functional annotations and differential gene expression data were evaluated. RESULTS: A significant association between the single nuclear polymorphism (SNP) rs1456896 and susceptibility to LN was observed in the two different cohorts (p = 9.32 * 10-3 and p = 3.00 * 10-2) and reinforced in combination (p = 1.36 * 10-3). In silico analysis indicates that rs1456896 is a regulatory variant and lower mRNA expressions of IKZF1 were observed in both peripheral blood mononuclear cells (PBMCs) and renal biopsies from SLE patients compared to normal controls. Although patients with the protective genotype AA of rs1456896 seemed to have more pronounced clinical manifestations and a lower ratio of histological classes III and IV, no significant associations between rs1456896 genotypes and sub-phenotypes of LN were detected. CONCLUSIONS: Our results suggest that the rs1456896 A allele is associated with protective susceptibility to LN. However, this association did not seem to be implicated in the disease and histopathological severity of LN in the current population. PMID- 27684962 TI - Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging. AB - Long-term in vivo imaging of cells is crucial for the understanding of cellular fate in biological processes in cancer research, immunology, or in cell-based therapies such as beta cell transplantation in type I diabetes or stem cell therapy. Traditionally, cell labeling with the desired contrast agent occurs ex vivo via spontaneous endocytosis, which is a variable and slow process that requires optimization for each particular label-cell type combination. Following endocytic uptake, the contrast agents mostly remain entrapped in the endolysosomal compartment, which leads to signal instability, cytotoxicity, and asymmetric inheritance of the labels upon cell division. Here, we demonstrate that these disadvantages can be circumvented by delivering contrast agents directly into the cytoplasm via vapor nanobubble photoporation. Compared to classic endocytic uptake, photoporation resulted in 50 and 3 times higher loading of fluorescent dextrans and quantum dots, respectively, with improved signal stability and reduced cytotoxicity. Most interestingly, cytosolic delivery by photoporation prevented asymmetric inheritance of labels by daughter cells over subsequent cell generations. Instead, unequal inheritance of endocytosed labels resulted in a dramatic increase in polydispersity of the amount of labels per cell with each cell division, hindering accurate quantification of cell numbers in vivo over time. The combined benefits of cell labeling by photoporation resulted in a marked improvement in long-term cell visibility in vivo where an insulin producing cell line (INS-1E cell line) labeled with fluorescent dextrans could be tracked for up to two months in Swiss nude mice compared to 2 weeks for cells labeled by endocytosis. PMID- 27684963 TI - How can educators support general practice (GP) trainees to develop resilience to prevent burnout? AB - CONTEXT: Burnout impacts adversely on professional and personal life, and holds implications for patient care. Current research on burnout mainly focuses on established general practitioners but it is unclear how early the signs of burnout really start. This work seeks to identify whether specific GP trainee groups are particularly at risk of burnout and the aspects of training they find stressful. METHODS: A longitudinal cohort study, collecting qualitative and quantitative data through a single mode of data collection (questionnaire) took place with trainees from all GP training years (ST1-3), across a vocational training scheme (n = 48). Data gathered included the Oldenburg Burnout Inventory (OLBI). RESULTS: Higher than anticipated levels of burnout were displayed by all trainees. A sub-group self reporting higher levels of burnout comprised all female, UK-trained-at-undergraduate GP trainees, with a partner but no children. Top reported stressors included knowledge/uncertainty, workload/time pressures and ePortfolio. Less than 50% of trainees perceived their burnout levels to be as high as their OLBI showing potential lack of insight. CONCLUSIONS: This research demonstrates that high levels of burnout are experienced in GP trainees as early as the first year of training. Early identification of burnout amongst trainees is essential by GP educators to help protect the future GP workforce. PMID- 27684965 TI - Imaging Cell Viability on Non-transparent Scaffolds - Using the Example of a Novel Knitted Titanium Implant. AB - Intervertebral disc degeneration and disc herniation is one of the major causes of lower back pain. Depletion of extracellular matrix, culminating in nucleus pulposus (NP) extrusion leads to intervertebral disc destruction. Currently available surgical treatments reduce the pain but do not restore the mechanical functionality of the spine. In order to preserve mechanical features of the spine, total disc or nucleus replacement thus became a wide interest. However, this arthroplasty era is still in an immature state, since none of the existing products have been clinically evaluated. This study intends to test the biocompatibility of a novel nucleus implant made of knitted titanium wires. Despite all mechanical advantages, the material has its limits for conventional optical analysis as the resulting implant is non-transparent. Here we present a strategy that describes in vitro visualization, tracking and viability testing of osteochondro-progenitor cells on the scaffold. This protocol can be used to visualize the efficiency of the cleaning protocol as well as to investigate the biocompatibility of these and other non-transparent scaffolds. Furthermore, this protocol can be used to show adherence pattern of cells as well as cell viability and proliferation rates on/in the scaffold. This in vitro biocompatibility testing assay provides a propitious tool to analyze cell-material interaction in non-transparent and opaque scaffolds. PMID- 27684964 TI - Attentional biases in children of depressed mothers: An event-related potential (ERP) study. AB - Although a number of studies have reported that children of depressed, compared to nondepressed, parents exhibit biased attention to sad facial stimuli, the direction of this bias remains unclear; some studies find evidence of preferential attention toward sad faces whereas others find evidence of attention avoidance. In the current study, we used event-related potentials (ERPs) to assess children's attention to emotional stimuli using a spatial cueing task. Across all indices of attention bias (N2pc and sustained posterior contralateral negativity [SPCN] time locked to face onset, P3b time locked to probe onset, reaction times [RTs] to probes), children of mothers with a history of major depressive disorder (MDD) during the child's life exhibited less attention to sad faces than children of never depressed mothers. For two of these indices (SPCN and RTs), the attention biases for the offspring of depressed mothers was not specific to sadness and was observed for all emotional expressions. Group differences in the ERP indices were maintained when controlling for the influence of mothers' and children's current symptoms of depression and anxiety, mothers' history of anxiety disorders, and children's history of MDD and anxiety disorders, suggesting that the results are specific to mothers' history of MDD. (PsycINFO Database Record PMID- 27684966 TI - Intestinal immunostimulatory activity of neutral polysaccharide isolated from traditionally fermented Korean brown rice vinegar. AB - In this study, diverse intestinal immunostimulatory activities were demonstrated for polysaccharides (KBV-CP) isolated from Korean brown rice vinegar. Monosaccharide composition analysis indicated that KBV-CP was composed mainly of neutral sugar units, primarily glucose and mannose. In vitro, KBV-CP significantly augmented the productions of immunoglobulin A (IgA) and IgA-related cytokines such as interleukin-6 (IL-6) and transforming growth factor-beta (TGF beta) in a dose-dependent manner. Furthermore, results of an in vitro co-culture system of intestinal Caco-2 cells and RAW 264.7 macrophage cells suggested that KBV-CP is not only cytotoxic to Caco-2 cells but also capable of being transported across the small intestinal barrier. Oral administration of KBV-CP every other day for 20 days induced the IgA production by Peyer's patch cells as well as in intestinal fluid and fecal extract. In addition, the production of IgA related cytokines such as TGF-beta and IL-6, and granulocyte macrophage colony stimulating factor was triggered. PMID- 27684968 TI - A Second Look at Pathology Reports and Slides. PMID- 27684967 TI - delta-MnO2-Mn3O4 Nanocomposite for Photochemical Water Oxidation: Active Structure Stabilized in the Interface. AB - Pure phase manganese oxides have been widely studied as water oxidation catalysts, but further improvement of their activities is much challenging. Herein, we report an effective method to improve the water oxidation activity by fabricating a nanocomposite of Mn3O4 and delta-MnO2 with an active interface. The nanocomposite was achieved by a partial reduction approach which induced an in situ growth of Mn3O4 nanoparticles from the surface of delta-MnO2 nanosheets. The optimum composition was determined to be 38% Mn3O4 and 62% delta-MnO2 as confirmed by X-ray photoelectron spectra (XPS) and X-ray absorption spectra (XAS). The delta-MnO2-Mn3O4 nanocomposite is a highly active water oxidation catalyst with a turnover frequency (TOF) of 0.93 s-1, which is much higher than the individual components of delta-MnO2 and Mn3O4. We consider that the enhanced water oxidation activity could be explained by the active interface between two components. At the phase interface, weak Mn-O bonds are introduced by lattice disorder in the transition of hausmannite phase to birnessite phase, which provides active sites for water oxidation catalysis. Our study illustrates a new view to improve water oxidation activity of manganese oxides. PMID- 27684970 TI - In Reply. PMID- 27684969 TI - Cross-reactivity of Anti-Treponema Immunohistochemistry With Non-Treponema Spirochetes: A Simple Call for Caution. PMID- 27684971 TI - Constructing Comments in a Pathology Report: Advice for the Pathology Resident. PMID- 27684972 TI - Contributions From the University of Michigan New Frontiers in Pathology 2015 Conference. PMID- 27684973 TI - Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification. AB - Molecular and morphologic interrogation has driven a much-needed reexamination of renal cell carcinoma (RCC). Indeed, the recently released 2016 World Health Organization classification now recognizes 12 distinct RCC subtypes, as well as several other emerging/provisional RCC entities. From a clinical perspective, accurate RCC classification may have important implications for patients and their families, including prognostic risk stratification, targeted therapeutics selection, and identification for genetic testing. In this review, we provide a conceptual framework for approaching RCC diagnosis and classification by categorizing RCCs as tumors with clear cytoplasm, papillary architecture, and eosinophilic (oncocytic) cytoplasm. The currently recognized 2016 World Health Organization classification for RCC subtypes is briefly discussed, including new diagnostic entities (clear cell papillary RCC, hereditary leiomyomatosis and RCC associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, and acquired cystic disease-associated RCC) and areas of evolving RCC classification, such as transcription elongation factor B subunit 1 (TCEB1)-mutated RCC/RCC with angioleiomyoma-like stroma/RCC with leiomyomatous stroma, RCC associated with anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement, thyroidlike follicular RCC, and RCC in neuroblastoma survivors. For each RCC subtype, relevant clinical, molecular, gross, and microscopic findings are reviewed, and ancillary studies helpful for its differential diagnosis are presented, providing a practical approach to modern RCC classification. PMID- 27684974 TI - Cytologic and Immunohistochemical Evaluation of Low-Grade Spindle Cell Lesions of the Gastrointestinal Tract. AB - Spindle cell lesions of the gastrointestinal tract are relatively uncommon compared with the frequency of their epithelial counterparts. Although gastrointestinal stromal tumors and leiomyomas are the most commonly encountered spindle cell lesions in the stomach and esophagus, respectively, there are other less common diagnostic entities that should be considered for accurate diagnoses as well as appropriate patient treatment and clinical follow-up. Given the morphologic overlap of low-grade spindle cell lesions on cytologic preparations, ancillary studies play a key role in differentiating these lesions from one another. PMID- 27684975 TI - Atypical Apocrine Adenosis: Diagnostic Challenges and Pitfalls. AB - Apocrine change in the breast is an extremely common finding. In most cases, the benign or malignant nature of the lesion is easily recognized. Apocrine adenosis is used to describe sclerosing adenosis with apocrine change. The term apocrine atypia is used when there is significant cytologic atypia in apocrine cells, characterized by a 3-fold nuclear enlargement, prominent/multiple nucleoli, and hyperchromasia. Atypical apocrine adenosis is diagnosed when apocrine adenosis and apocrine atypia are superimposed. However, there are no definite criteria to distinguish atypical apocrine adenosis from apocrine ductal carcinoma in situ. Immunohistochemical markers can be confounding and may lead to erroneous diagnoses. Atypical apocrine features in sclerosing lesions may be misinterpreted as invasive carcinoma if the underlying lesion is not recognized. In the absence of definite features of malignancy, the diagnosis of apocrine ductal carcinoma in situ may be extremely difficult. In the present article, we review atypical apocrine adenosis focusing on diagnostic challenges and their implications on clinical management. PMID- 27684976 TI - Papillary Lesions of the Breast: A Practical Approach to Diagnosis. AB - Papillary lesions of the breast span the spectrum of benign, atypical, and malignant. Subclassification of these lesions may be diagnostically challenging, especially with limited sampling via core biopsy. This review outlines the features of papillary lesions of the breast and provides a practical approach to distinguishing diagnostically challenging lesions by using key morphologic features and, when helpful, immunohistochemical studies. PMID- 27684977 TI - Blood and Bone Marrow Evaluation for Eosinophilia. AB - Evaluation of peripheral blood and bone marrow for an indication of persistent eosinophilia can be a challenging task because there are many causes of eosinophilia and the morphologic differences between reactive and neoplastic causes are often subtle or lack specificity. The purpose of this review is to provide an overview of the differential diagnosis for eosinophilia, to recommend specific steps for the pathologist evaluating blood and bone marrow, and to emphasize 2 important causes of eosinophilia that require specific ancillary tests for diagnosis: myeloproliferative neoplasm with PDGFRA rearrangement and lymphocyte-variant hypereosinophilic syndrome. PMID- 27684978 TI - Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective. AB - CONTEXT: -Intraductal tubulopapillary neoplasm (ITPN) is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management. OBJECTIVE: -To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options. DATA SOURCES: -Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials. CONCLUSIONS: -Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options. PMID- 27684979 TI - Plasmablastic Lymphoma: A Review of Clinicopathologic Features and Differential Diagnosis. AB - Plasmablastic lymphoma (PBL) is a challenging diagnosis given its rarity and lack of expression of markers that are usually used by pathologists in establishing hematopoietic lineage. However, knowledge of the characteristic clinical setting, sites of involvement, and morphologic features of plasmablastic lymphoma can aid in the correct diagnosis of a suspected large cell lymphoma that is negative for B-cell- and T-cell-specific antigens. Herein, we review the clinical and pathologic features of plasmablastic lymphoma with an emphasis on the differential diagnosis of hematolymphoid neoplasms with immunoblastic morphology and/or evidence of plasmacytic differentiation by immunophenotype. PMID- 27684980 TI - A Historical Perspective and Expose on Serrated Polyps of the Colorectum. AB - This article offers a historical perspective on the discovery of 3 types of serrated colorectal polyps recognized in the past 60 years. The first to be discovered was the hyperplastic polyp, which is still the most commonly encountered serrated polyp. In the past 20 years, the carcinoma-associated sessile serrated adenoma/polyp has been recognized, but its diagnosis can be difficult owing to overlapping histologic features with hyperplastic polyps. Less is known about the third type, the traditional serrated adenoma, because it is far less common than the other 2 types, and its association with cancer is currently under investigation. PMID- 27684981 TI - Survey of Irradiation Practice for the Prevention of Transfusion-Associated Graft versus-Host Disease. AB - CONTEXT: -Transfusion-associated graft-versus-host disease is a rare, often fatal complication of cellular blood product transfusion. The requirement that at-risk groups receive irradiated products reduces the incidence of transfusion associated graft-versus-host disease. A comprehensive survey of irradiation practices has not been performed since 1989; meanwhile, new indications for irradiation have emerged. OBJECTIVE: -To assess current irradiation practices at College of American Pathologists member institutions. Changes in irradiation practice indicated by comparing results of a survey of irradiation practices in 1989 with those of a survey performed in 2014 may reveal how the field has developed and what areas (if any) remain to be improved. DESIGN: -A supplemental College of American Pathologists survey was sent out with questions regarding irradiation practices for specific conditions and circumstances. The questions included conditions for which irradiation is generally considered required for the prevention of transfusion-associated graft-versus-host disease as well as those not considered to be a special risk. RESULTS: -An average of 2100 organizations responded to each question regarding their irradiation practices. Irradiation for transfusion from blood relatives, human leukocyte antigen-matched products, preterm infants, and Hodgkin disease were the most common indications cited. A few organizations had universal irradiation, whereas others irradiated products by floor/unit or by service. CONCLUSIONS: -For some at-risk populations irradiation of cellular blood products is more common than in 1989, whereas for others this practice has been reduced. Although gains have been made since the last national survey of irradiation practices, work remains to eliminate the possibility of transfusion-associated graft-versus-host disease from known at risk populations. PMID- 27684982 TI - Physician Satisfaction With Clinical Laboratory Services: A College of American Pathologists Q-Probes Study of 81 Institutions. AB - CONTEXT: -Assessment of customer satisfaction is a vital component of the laboratory quality improvement program. OBJECTIVE: -To survey the level of physician satisfaction with hospital clinical laboratory services. DESIGN: Participating institutions provided demographic information and survey results of physician satisfaction, with specific features of clinical laboratory services individually rated on a scale of 5 (excellent) to 1 (poor). RESULTS: -Eighty-one institutions submitted 2425 surveys. The median overall satisfaction score was 4.2 (10th percentile, 3.6; 90th percentile, 4.6). Of the 16 surveyed areas receiving the highest percentage of excellent/good ratings (combined scores of 4 and 5), quality of results was highest along with test menu adequacy, staff courtesy, and overall satisfaction. Of the 4 categories receiving the lowest percentage values of excellent/good ratings, 3 were related to turnaround time for inpatient "STAT" (tests performed immediately), outpatient STAT, and esoteric tests. The fourth was a new category presented in this survey: ease of electronic order entry. Here, 11.4% (241 of 2121) of physicians assigned below-average (2) or poor (1) scores. The 5 categories deemed most important to physicians included quality of results, turnaround times for inpatient STAT, routine, and outpatient STAT tests, and clinical report format. Overall satisfaction as measured by physician willingness to recommend their laboratory to another physician remains high at 94.5% (2160 of 2286 respondents). CONCLUSIONS: -There is a continued trend of high physician satisfaction and loyalty with clinical laboratory services. Physician dissatisfaction with ease of electronic order entry represents a new challenge. Test turnaround times are persistent areas of dissatisfaction, representing areas for improvement. PMID- 27684983 TI - Automated Bright-Field Dual-Color In Situ Hybridization for MDM2: Interobserver Reproducibility and Correlation With Fluorescence In Situ Hybridization in a Series of Soft Tissue Consults. AB - CONTEXT: -Atypical lipomatous tumors/well-differentiated liposarcomas contain alterations in the 12q13-15 region resulting in amplification of MDM2 and nearby genes. Identifying MDM2 amplification is a useful ancillary test, as the histologic mimics of atypical lipomatous tumors/well-differentiated liposarcomas have consistently shown a lack of MDM2 amplification. OBJECTIVE: -To assess the interobserver reproducibility of a bright-field assay for MDM2 amplification (dual-color, dual-hapten in situ hybridization [DDISH]) among reviewers with varying degrees of experience with the assay and to assess the concordance of MDM2 DDISH with MDM2 fluorescence in situ hybridization (FISH). DESIGN: -In total, 102 cases were assessed in parallel for MDM2 by FISH and DDISH. MDM2 amplification was defined as an MDM2 to chromosome 12 ratio of 2.0 or greater, whereas an MDM2 to chromosome 12 ratio of less than 2 was nonamplified. Fluorescence in situ hybridization was scored in the routine clinical laboratory and DDISH was evaluated by 3 different pathologists blinded to the final diagnosis and FISH results. RESULTS: -Fluorescence in situ hybridization categorized 27 cases (26%) as MDM2 amplified and 75 cases (74%) as nonamplified; the consensus DDISH diagnosis was 98% concordant with FISH. Agreement between MDM2 DDISH by each reviewer and MDM2 FISH was highly concordant (99%, 98%, and 98%, respectively, for reviewers 1, 2 and 3). The kappa agreement of the 3 reviewers scoring DDISH was excellent (kappa = 0.949, 0.95, and 0.95, respectively, for reviewers 1, 2, and 3). CONCLUSIONS: -This study highlights excellent concordance between DDISH and FISH in MDM2 copy number assessment. Moreover, excellent interobserver reproducibility of the DDISH assay was found among reviewers with varying levels of experience evaluating bright-field assays. PMID- 27684984 TI - Application of the Bethesda Classification for Thyroid Fine-Needle Aspiration: Institutional Experience and Meta-analysis. AB - CONTEXT: -Fine-needle aspiration (FNA) biopsies have been an important component in the preoperative evaluation of thyroid nodules. Until the introduction of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) in 2008, individual institutions had developed their own diagnostic categories. The BSRTC proposed 6 categories in an attempt to standardize reporting of thyroid FNA. OBJECTIVE: -To present a 15-year experience of thyroid FNA at one institution, including data before and after introduction of the BSRTC. The risk of malignancy is compared with the meta-analysis of high-quality published data. DATA SOURCES: -Data sources were PubMed, a manual search of references, and institutional data. CONCLUSIONS: -The diagnostic categories developed at our institution were similar to those proposed by the BSRTC, with best fit into the 6 categories easily accomplished and reported in the final 2 years of the study. Significant differences were noted in the frequencies of cases in diagnostic categories Benign (II; P = .003), Suspicious for follicular neoplasm/Follicular neoplasm (IV; P < .001), and Malignant (VI; P = .003) after the introduction of the BSRTC. Eighteen published articles met the criteria for inclusion in the meta-analysis. The risk of malignancy in each category in our institution was similar to that determined in the meta-analysis, except for Insufficient for diagnosis (I; 20% versus 9%-14%). Meta-analysis showed an overlapping 95% CI of risk of malignancy between Atypia of undetermined significance/Follicular lesion of undetermined significance (III; 11%-23%) and Suspicious for follicular neoplasm/Follicular neoplasm (IV; 20%-29%), suggesting similar risks of malignancy. The use of newer molecular tests for these indeterminate cases may further refine risk assessment. PMID- 27684985 TI - Infantile Digital Fibroma: A Rare Fibromatosis. AB - Infantile digital fibroma is a rare benign lesion that usually occurs during the first 2 years of life. It can be multiple, but it is usually a single lesion. If it grows large enough it can cause joint deformities or interfere with everyday activities. Microscopically, the neoplastic cells usually have inclusion bodies that are best highlighted with a Masson trichrome stain but can often be seen on hematoxylin-eosin staining. Treatment for this entity is usually watchful waiting because of its ability to spontaneously regress, but excision is recommended if the lesion is symptomatic. More recently, fluorouracil or injectable steroids have shown great promise in inducing regression without the complications that accompany surgery. PMID- 27684986 TI - Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review. AB - Mixed adenoneuroendocrine carcinomas (MANECs) are composite neoplasms with areas of adenocarcinoma or squamous cell carcinoma intermingled with neuroendocrine carcinoma or neuroendocrine tumor, each composing at least 30% of the neoplasm. MANECs are very infrequent overall, and they are more commonly diagnosed in the appendix, colon, and stomach. Biliary MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are seldom identified in the normal biliary tract. They can show one of the 3 different architectural patterns described in Lewin's original classification: collision tumors, combined lesions, or amphicrine neoplasms. The neuroendocrine component is usually of a high grade, with small or large cell cytomorphology, whereas the adenocarcinoma component is either an intestinal or biliary type. Clinical presentation is characterized by locally advanced disease at the time of initial diagnosis. Recent studies suggest that treatment should be guided by the most aggressive histologic component. PMID- 27684988 TI - Fluency tasks generate beta-gamma activity in language-related cortical areas of patients during stereo-EEG monitoring. AB - A quantitative method was developed to map cortical areas responsive to cognitive tasks during intracerebral stereo-EEG recording sessions in drug-resistant patients candidate for epilepsy surgery. Frequency power changes were evaluated with a computer-assisted analysis in 7 patients during phonemic fluency tasks. All patients were right-handed and were explored with depth electrodes in the dominant frontal lobe. We demonstrate that fluency tasks enhance beta-gamma frequencies and reduce background activities in language network regions of the dominant hemisphere. Non-reproducible changes were observed in other explored brain areas during cognitive tests execution. PMID- 27684987 TI - Sulfate Separation by Selective Crystallization with a Bis-iminoguanidinium Ligand. AB - A simple and effective method for selective sulfate separation from aqueous solutions by crystallization with a bis-guanidinium ligand, 1,4-benzene bis(iminoguanidinium) (BBIG), is demonstrated. The ligand is synthesized as the chloride salt (BBIG-Cl) by in situ imine condensation of terephthalaldehyde with aminoguanidinium chloride in water, followed by crystallization as the sulfate salt (BBIG-SO4). Alternatively, BBIG-Cl is synthesized ex situ in larger scale from ethanol. The sulfate separation ability of the BBIG ligand is demonstrated by selective and quantitative crystallization of sulfate from seawater. The ligand can be recycled by neutralization of BBIG-SO4 with aqueous NaOH and crystallization of the neutral bis-iminoguanidine, which can be converted back into BBIG-Cl with aqueous HCl and reused in another separation cycle. Finally, (35)S-labeled sulfate and beta liquid scintillation counting are employed for monitoring the sulfate concentration in solution. Overall, this protocol will instruct the user in the necessary skills to synthesize a ligand, employ it in the selective crystallization of sulfate from aqueous solutions, and quantify the separation efficiency. PMID- 27684989 TI - Effect of fly ash on properties of crushed brick and reclaimed asphalt in pavement base/subbase applications. AB - Fly Ash (FA), an abundant by-product with no carbon footprint, is a potential stabilizer for enhancing the physical and geotechnical properties of pavement aggregates. In this research, FA was used in different ratios to stabilize crushed brick (CB) and reclaimed asphalt pavement (RAP) for pavement base/subbase applications. The FA stabilization of CB and RAP was targeted to improve the strength and durability of these recycled materials for pavement base/subbase applications. The Unconfined Compressive Strength (UCS) and resilient modulus (MR) development of the stabilized CB and RAP aggregates was studied under room temperature and at an elevated temperatures of 40 degrees C, and results compared with unbound CB and RAP. Analysis of atomic silica content showed that when the amount of silica and alumina crystalline was increased, the soil structure matrix deteriorated, resulting in strength reduction. The results of UCS and MR testing of FA stabilized CB and RAP aggregates indicated that FA was a viable binder for the stabilization of recycled CB and RAP. CB and RAP stabilized with 15% FA showed the highest UCS results at both room temperature and at 40 degrees C. Higher temperature curing was also found to result in higher strengths. PMID- 27684990 TI - Nanosized zero-valent iron as Fenton-like reagent for ultrasonic-assisted leaching of zinc from blast furnace sludge. AB - Ultrasonic-assisted sulphuric acid leaching combined with a Fenton-like process, utilizing nanoscale zero-valent iron (nZVI), was investigated to enhance the leaching of zinc from the blast furnace sludge (BFS). The leaching of iron (Fe) and zinc (Zn) from the sludge was investigated using Milli-Q water/BFS ratio of 10 and varying the concentration of hydrogen peroxide, sulphuric acid, the temperature, the input energy for ultrasound irradiation, and the presence or absence of nZVI as a Fenton reagent. The results showed that with 1g/l addition of nZVI and 0.05M of hydrogen peroxide, the kinetic rate of Zn leaching increased with a maximum dissolution degree of 80.2%, after 5min treatment. In the absence of nZVI, the maximum dissolution degree of Zn was 99.2%, after 15min treatment with 0.1M of hydrogen peroxide. The rate of Zn leaching at several concentrations of hydrogen peroxide is accelerated in the presence of nZVI although a reduction in efficiency was observed. The loss of Fe was no more than 3%. On the basis of these results, the possible route for BFS recycling has been proposed (BFS slurry mixed with sulphuric acid and hydrogen peroxide is recirculated under ultrasonic irradiation then separated). PMID- 27684991 TI - Procedure for Adaptive Laboratory Evolution of Microorganisms Using a Chemostat. AB - Natural evolution involves genetic diversity such as environmental change and a selection between small populations. Adaptive laboratory evolution (ALE) refers to the experimental situation in which evolution is observed using living organisms under controlled conditions and stressors; organisms are thereby artificially forced to make evolutionary changes. Microorganisms are subject to a variety of stressors in the environment and are capable of regulating certain stress-inducible proteins to increase their chances of survival. Naturally occurring spontaneous mutations bring about changes in a microorganism's genome that affect its chances of survival. Long-term exposure to chemostat culture provokes an accumulation of spontaneous mutations and renders the most adaptable strain dominant. Compared to the colony transfer and serial transfer methods, chemostat culture entails the highest number of cell divisions and, therefore, the highest number of diverse populations. Although chemostat culture for ALE requires more complicated culture devices, it is less labor intensive once the operation begins. Comparative genomic and transcriptome analyses of the adapted strain provide evolutionary clues as to how the stressors contribute to mutations that overcome the stress. The goal of the current paper is to bring about accelerated evolution of microorganisms under controlled laboratory conditions. PMID- 27684992 TI - A Method of Targeted Cell Isolation via Glass Surface Functionalization. AB - One of the limiting factors to the adoption and advancement of personalized medicine is the inability to develop diagnostic tools to probe individual nuances in expression from patient to patient. Current methodologies that try to separate cells to fill this niche result in disruption of physiological expression, making the separation technique useless as a diagnostic tool. In this protocol, we describe the functionalization and optimization of a surface for the cellular capture and release. This functionalized surface integrates biotinylated antibodies with a glass surface functionalized with an aminosilane (APTES), desthiobiotin and streptavidin. Cell release is facilitated through the introduction of biotin, allowing the recollection and purification of cells captured by the surface. This release is done through the targeting of the secondary moiety desthiobiotin, which results in a much more gentle release paradigm. This reduction in harsh reagents and shear forces reduces changes in cellular expression. The functionalized surface captures up to 80% of cells in a single cell mixture and has demonstrated 50% capture in a dual-cell mixture. Applications of this technology to xenografts and cancer separation studies are investigated. Quantification techniques for surface verification such as plate reader and ImageJ analyses are described as well. PMID- 27684993 TI - Mesenteric Tumor Deposits in Midgut Small Intestinal Neuroendocrine Tumors Are a Stronger Indicator Than Lymph Node Metastasis for Liver Metastasis and Poor Prognosis. AB - Mesenteric tumor deposits (MTDs) are not included in the American Joint Committee on Cancer (AJCC) staging system for midgut small intestinal neuroendocrine tumors (NETs). We examined the prognostic significance of MTDs associated with midgut NETs. Hematoxylin and eosin slides from 132 resected jejunal/ileal NETs were reviewed for AJCC tumor stage, lymph node (LN) metastasis, MTDs, and hepatic metastases. MTDs were defined as discrete irregular mesenteric tumor nodules discontinuous from the primary tumor. Clinical or pathologic evidence of metastases and survival data were abstracted from electronic medical records. The cohort included 72 male and 60 female patients with a median age of 60 years. LN metastasis, MTDs, and liver metastasis were present in 80%, 68%, and 58% of patients, respectively. Female sex and presence of MTDs were independent predictors of liver metastasis. The odds ratio for hepatic metastasis in the presence of MTDs was 16.68 (95% confidence interval [CI], 4.66-59.73) and 0.81 (95% CI, 0.20-3.26) for LN metastasis. Age, MTDs, and hepatic metastasis were associated with disease-specific survival (DSS) in univariate analysis. Primary tumor histologic grade, pT3/T4 stage, and LN metastasis were not associated with DSS. Multivariate analysis of liver metastasis-free survival stratified by tumor grade showed that MTDs were associated with adverse outcomes. The hazard ratio for MTDs was 4.58 (95% CI, 1.89-11.11), compared with 0.98 (95% CI, 0.47-2.05) for LN metastasis. MTDs, but not LN metastasis, in midgut NETs are a strong predictor for hepatic metastasis and are associated with poor DSS. PMID- 27684994 TI - Optimization of breathing instructions and timing of late arterial phase acquisition on gadobutrol-enhanced MRI of the liver. AB - PURPOSE: To compare a protocol with higher concentration macrocyclic gadolinium based contrast agent (GBCA) [study group] to the traditional protocol with lower concentration linear GBCAs [control group] for breath-held arterial phase magnetic resonance imaging. MATERIAL AND METHODS: A total of 136 patients were quantitatively evaluated for image quality (IQ), breathing artifacts (BA), and timing of the arterial phase (Tap). Quantitative analysis was also performed. RESULTS: No significant differences in IQ, BA and Tap (P>.05). Study group exhibited less enhancement of the aorta (P=.0091) and smaller standard deviation for the portal vein enhancement (P=.0173). CONCLUSION: Similar arterial-phase image quality can be achieved with a macrocyclic GBCA compared to traditional linear GBCA. PMID- 27684995 TI - Applicability and discriminative value of a semiautomatic three-dimensional spherical volume for the assessment of the apparent diffusion coefficient in suspicious breast lesions-feasibility study. AB - INTRODUCTION: To evaluate the feasibility and accuracy of a semiautomatic, three dimensional volume of interest (3D sphere) for measuring the apparent diffusion coefficient (ADC) in suspicious breast lesions compared to conventional single slice two-dimensional regions of interest (2D ROIs). METHOD: This institutional review-board-approved study included 56 participants with Breast Imaging Reporting and Data System 4/5 lesion. All received diffusion-weighted imaging magnetic resonance imaging prior to biopsy (b=0-1500 s/mm2). ADC values were measured in the lesions with both methods. Reproducibility and accuracies were compared. RESULTS: Area under the curve was 0.93 [95% confidence interval (CI) 0.86-0.99] for the 3D sphere and 0.91 (95% CI 0.84-0.98) for the 2D ROIs without significantly differing reproducibility (P=.45). CONCLUSION: A semiautomatic 3D sphere could reliably estimate ADC values in suspicious breast lesions without significant difference compared to conventional 2D ROIs. PMID- 27684996 TI - Evaluation of aqueductal cerebrospinal fluid flow dynamics with phase-contrast cine magnetic resonance imaging in normal pediatric cases. AB - PURPOSE: This study aimed to determine differences according to age groups and gender in the parameters of aqueductal cerebrospinal fluid (CSF) flow in childhood using phase-contrast cine magnetic resonance imaging (MRI) method. MATERIALS AND METHODS: This prospective study included 47 boys and 36 girls for a total of 83 healthy children. The cases were divided into three groups depending on age as infants (1-12 months), children (12-120 months), and adolescents (120 204 months). To quantitatively evaluate CSF flow, images in the transverse plane were taken at the cerebral aqueduct level using the phase-contrast MR angiography technique in a 1.5-T MR unit. Peak and average velocity (cm/s), cranial direction, caudal direction and net volume (ml), and aqueduct area (mm2) were calculated. To assess differences between the groups, a one-way analysis of variance and least significant difference tests were used. RESULTS: A statistically significant difference was determined between children and adolescents in peak velocity and caudal direction volume (P=.012 and P=.039, respectively) and between infants and children in cranial direction volume (P=.036). Peak velocity, cranial direction, and net volume were higher in boys (P=.050, P=.016, and P=.029, respectively). There were no differences by age and gender in the aqueduct area. CONCLUSION: In conclusion, this study determined the normal values for the CSF flow parameters of velocity, volume, and aqueduct area using phase-contrast MRI in healthy children. Velocity and volume parameters varied according to age and sex and were not affected in the aqueductal area. PMID- 27684997 TI - Nd3+-Sensitized Upconversion Nanostructure as a Dual-Channel Emitting Optical Probe for Near Infrared-to-Near Infrared Fingerprint Imaging. AB - Lanthanide upconversion nanophosphors (Ln-UCNPs) have attracted great attention in a variety of fields, benefiting from low background fluorescence interference and a high signal-to-noise ratio of upconversion luminescence. However, the establishment of Ln-UCNPs with dual near-infrared (NIR) emission channels still remains challenging. Herein, we report the design and synthesis of Nd3+ sensitized NaYbF4:Tm@NaYF4:Yb@NaNdF4:Yb hierarchical-structured nanoparticles that emit NIR luminescence at 696 and 980 nm under excitation at 808 nm. The sensitizer-rich NaYbF4 core promotes efficient energy transfer to Tm3+. The interlayer of NaYF4:Yb effectively prevents the cross-relaxation process from Tm3+ to Nd3+ and thus enhances the luminescence emission. The introduction of Nd3+ ion as the sensitizer transforms the excitation wavelength from 980 to 808 nm, which subtly averts the laser-induced thermal effect and offers a new pathway for the NIR emission channel at 980 nm. The as-prepared nanoparticles were further applied in developing latent and blood fingerprint images, which exhibited high signal-to-noise ratio and distinguishable details under 808 nm excitation with negligible thermal damage to the sample. Our work provides a promising strategy to realize NIR-to-NIR dual-channel emissions in Ln-UCNPs. With further functionalization, such nanoparticles are expected to have great potential in forensic and biological sciences. PMID- 27684999 TI - Decreased effectiveness of the influenza A(H1N1)pdm09 strain in live attenuated influenza vaccines: an observational bias or a technical challenge? PMID- 27684998 TI - Transition to Parenthood and HIV Infection in Rural Zimbabwe. AB - BACKGROUND: The relationship between the risk of acquiring human immunodeficiency virus (HIV) infection and people's choices about life course events describing the transition to parenthood-sexual debut, union (in the form of marriage, cohabitation, or long-term relationship), and parenthood-is still unclear. A crucial role in shaping this relationship may be played by the sequence of these events and by their timing. This suggests the opportunity to focus on the life courses in their entirety rather than on the specific events, thus adopting a holistic approach that regards each individual's life course trajectory as a whole. METHODS: We summarise the individual life courses describing the transition to parenthood using ordered sequences of the three considered events. We aim to (i) investigate the association between the sequences and HIV infection, and (ii) understand how these sequences interact with known mechanisms for HIV transmission, such as the length of sexual exposure and the experience of non-regular sexual partnerships. For this purpose, we use data from a general population cohort study run in Manicaland (Zimbabwe), a Sub-Saharan African area characterised by high HIV prevalence. RESULTS: For both genders, individuals who experienced either premarital or delayed childbearing have higher HIV risk compared to individuals following more standard transitions. This can be explained by the interplay of the sequences with known HIV proximate determinants, e.g., a longer exposure to sexual activity and higher rates of premarital sex. Moreover, we found that people in the younger birth cohorts experience more normative and safer sequences. CONCLUSIONS: The shift of younger generations towards more normative transitions to parenthood is a sign of behaviour change that might have contributed to the observed reduction in HIV prevalence in the area. On the other hand, for people with less normative transitions, targeted strategies are essential for HIV prevention. PMID- 27685000 TI - Multiscale Simulations on Spectral Tuning and the Photoisomerization Mechanism in Fluorescent RNA Spinach. AB - Fluorescent RNA aptamer Spinach can bind and activate a green fluorescent protein (GFP)-like chromophore (an anionic DFHBDI chromophore) displaying green fluorescence. Spectroscopic properties, spectral tuning, and the photoisomerization mechanism in the Spinach-DFHBDI complex have been investigated by high-level QM and hybrid ONIOM(QM:AMBER) methods (QM method: (TD)DFT, SF BHHLYP, SAC-CI, LT-DF-LCC2, CASSCF, or MS-CASPT2), as well as classical molecular dynamics (MD) simulations. First, our benchmark calculations have shown that TD DFT and spin-flip (SF) TD-DFT (SF-BHHLYP) failed to give a satisfactory description of absorption and emission of the anionic DFHBDI chromophore. Comparatively, SAC-CI, LT-DF-LCC2, and MS-CASPT2 can give more reliable transition energies and are mainly used to further study the spectra of the anionic DFHBDI chromophore in Spinach. The RNA environmental effects on the spectral tuning and the photoisomerization mechanism have been elucidated. Our simulations show that interactions of the anionic cis-DFHBDI chromophore with two G-quadruplexes as well as a UAU base triple suppress photoisomerization of DFHBDI. In addition, strong hydrogen bonds between the anionic cis-DFHBDI chromophore and nearby nucleotides facilitate its binding to Spinach and further inhibit the cis-trans photoisomerization of DFHBDI. Solvent molecules, ions, and loss of key hydrogen bonds with nearby nucleotides could induce dissociation of the anionic trans-DFHBDI chromophore from the binding site. These results provide new insights into fluorescent RNA Spinach and may help rational design of other fluorescent RNAs. PMID- 27685001 TI - Classification and quantification of palm oil adulteration via portable NIR spectroscopy. AB - Short wave near infrared spectroscopy (NIR) method was used to detect the presence of lard adulteration in palm oil. MicroNIR was set up in two different scan modes to study the effect of path length to the performance of spectral measurement. Pure and adulterated palm oil sample were classified using soft independent modeling class analogy (SIMCA) algorithm with model accuracy more than 0.95 reported for both transflectance and transmission modes. Additionally, by employing partial least square (PLS) regression, the coefficient of determination (R2) of transflectance and transmission were 0.9987 and 0.9994 with root mean square error of calibration (RMSEC) of 0.5931 and 0.6703 respectively. In order to remove the uninformative variables, variable selection using cumulative adaptive reweighted sampling (CARS) has been performed. The result of R2 and RMSEC after variable selection for transflectance and transmission were improved significantly. Based on the result of classification and quantification analysis, the transmission mode has yield better prediction model compared to the transflectance mode to distinguish the pure and adulterated palm oil. PMID- 27685002 TI - Spectroscopic investigation on porphyrins nano-assemblies onto gold nanorods. AB - The interaction between gold nanorods (Au NRs), synthesized by a conventional seeded growth protocol, and the anionic tetrakis-(4-sulfonatophenyl)porphyrin (TPPS4) has been investigated through various spectroscopic techniques. At neutral pH, the formation of H-aggregates and the inclusion of porphyrin monomers in CTAB micelles covering the nanorods have been evidenced. Under mild acidic conditions (pH=3) a nano-hybrid assembly of porphyrin J-aggregates and Au NRs has been revealed. For the sake of comparison, Cu(II) and Zn(II) metal porphyrin derivatives as well as a cationic porphyrin have been studied in the same experimental conditions, showing that: i) CuTPPS4 forms porphyrin H-dimers onto the Au NRs; ii) ZnTPPS4 undergoes to demetallation, followed by acidification of the central core and eventually aggregation onto Au NRs; iii) cationic porphyrin does not interact with Au NRs. PMID- 27685003 TI - Resonance Raman spectroscopy study of protonated porphyrin. AB - Resonance Raman microscopy was used to study the resonance Raman scattering of the diacid (diprotonated form) of free-base porphyrin (21H,23H-porphine) in a crystal powder and KBr pellets. Intensive lines in the spectral range between 100/1000cm-1 have been detected and assigned as spectral manifestation of out-of plane modes. The Raman spectra were simulated by means of DFT methods and compared with the experimental data. It is evident from experimental and theoretical results that the activation of out-of-plane modes arises from saddle distortion of the porphyrin macrocycle upon formation of its diprotonated form. PMID- 27685004 TI - Pre-resonance enhancement of exceptional intensity in Aggregation-Induced Raman Optical Activity (AIROA) spectra of lutein derivatives. AB - Recently reported new phenomenon of Aggregation-Induced Raman Optical Activity is demonstrated here for the first time in the pre-resonance conditions for lutein diacetate and 3'-epi-lutein supramolecular self-assembles. We demonstrate that minor alterations in the lutein structure (e.g. acetylation of hydroxyl groups or different configuration at one of the chiral center) can lead to definitely different spectral profiles and optical properties due to formation of aggregates of different structure and type. Lutein forms only H-aggregates, lutein diacetate only J-aggregates, while 3'-epi-lutein can occur in both forms simultaneously. Variety of aggregates' structures is so large that not only the type of aggregation is different, but also their chirality. It is remarkable that even in the pre-resonance conditions, aggregation of lutein derivatives can lead to the intense ROA signal, and moreover, 3'-epi-lutein demonstrated the highest resonance ROA CID ratio that has ever been reported. PMID- 27685005 TI - Changes in healthcare access and utilization among participants in a public housing relocation program in Atlanta, Georgia. AB - Using survey data from participants in a public housing relocation program in Atlanta, Georgia, we examine post-relocation changes in healthcare access (having a usual source of care, having an unmet need) and utilization (receiving a medical exam). Although participants moved to safer, less impoverished neighborhoods, some participants experienced improvements in access and utilization whereas others experienced declines. The supply of healthcare providers in the new neighborhood and having health insurance were associated with improvements in access for this population. Future relocation efforts may seek to assist individuals with choosing a new neighborhood that has accessible healthcare resources for low-income populations. PMID- 27685006 TI - Unexpected, Latent Radical Reaction of Methane Propagated by Trifluoromethyl Radicals. AB - Thorough mechanistic studies and DFT calculations revealed a background radical pathway latent in metal-catalyzed oxidation reactions of methane at low temperatures. Use of hydrogen peroxide with TFAA generated a trifluoromethyl radical (*CF3), which in turn reacted with methane gas to selectively yield acetic acid. It was found that the methyl carbon of the product was derived from methane, while the carbonyl carbon was derived from TFAA. Computational studies also support these findings, revealing the reaction cycle to be energetically favorable. PMID- 27685007 TI - Corrigendum. PMID- 27685008 TI - Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men. AB - INTRODUCTION/PURPOSE: Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 +/- 4 yr; VO2max, 48 +/- 2 mL.kg.min) after repeated prolonged exercise). METHODS: A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. VO2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. RESULTS: The daily duration of exercise was 10 h and 31 +/- 37 min, and the mean intensity was 53% +/- 1% of VO2max. Body weight remained unchanged. VO2max and maximal fat oxidation rate decreased by 6% +/- 2% (P = 0.04) and 32% +/- 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 +/- 77 MUmol.L to 160 +/- 38 MUmol.L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and beta-hydroxy-acyl-CoA dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. CONCLUSIONS: Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise. PMID- 27685009 TI - Effect of Dry Needling on Thigh Muscle Strength and Hip Flexion in Elite Soccer Players. AB - PURPOSE: Increase in muscle force, endurance, and flexibility is desired in elite athletes to improve performance and to avoid injuries, but it is often hindered by the occurrence of myofascial trigger points. Dry needling (DN) has been shown effective in eliminating myofascial trigger points. METHODS: This randomized controlled study in 30 elite youth soccer players of a professional soccer Bundesliga Club investigated the effects of four weekly sessions of DN plus water pressure massage on thigh muscle force and range of motion of hip flexion. A group receiving placebo laser plus water pressure massage and a group with no intervention served as controls. Data were collected at baseline (M1), treatment end (M2), and 4 wk follow-up (M3). Furthermore, a 5-month muscle injury follow-up was performed. RESULTS: DN showed significant improvement of muscular endurance of knee extensors at M2 (P = 0.039) and M3 (P = 0.008) compared with M1 (M1:294.6 +/- 15.4 N.m.s, M2:311 +/- 25 N.m.s; M3:316.0 +/- 28.6 N.m.s) and knee flexors at M2 compared with M1 (M1:163.5 +/- 10.9 N.m.s, M2:188.5 +/- 16.3 N.m.s) as well as hip flexion (M1: 81.5 degrees +/- 3.3 degrees , M2:89.8 degrees +/- 2.8 degrees ; M3:91.8 degrees +/- 3.8 degrees ). Compared with placebo (3.8 degrees +/- 3.8 degrees ) and control (1.4 degrees +/- 2.9 degrees ), DN (10.3 degrees +/- 3.5 degrees ) showed a significant (P = 0.01 and P = 0.0002) effect at M3 compared with M1 on hip flexion; compared with nontreatment control (-10 +/- 11.9 N.m), DN (5.2 +/- 10.2 N.m) also significantly (P = 0.049) improved maximum force of knee extensors at M3 compared with M1. During the rest of the season, muscle injuries were less frequent in the DN group compared with the control group. CONCLUSION: DN showed a significant effect on muscular endurance and hip flexion range of motion that persisted 4 wk posttreatment. Compared with placebo, it showed a significant effect on hip flexion that persisted 4 wk posttreatment, and compared with nonintervention control, it showed a significant effect on maximum force of knee extensors 4 wk posttreatment in elite soccer players. PMID- 27685010 TI - Exercise and Transversus Abdominis Muscle Atrophy after 60-d Bed Rest. AB - PURPOSE: This study aimed to investigate atrophy in the deep abdominal muscles, spinal extensors, and the effect of high-load resistive exercise with and without whole-body vibration after 60 d of strict bed rest. METHODS: Twenty-four subjects underwent 60 d of head-down tilt bed rest and performed either resistive vibration exercise (RVE), resistive exercise only (RE), or no exercise control (2nd Berlin BedRest Study). The thickness of the transversus abdominis, internal oblique, and erector spinae muscles and the area of the multifidus muscle were measured bilaterally via real-time ultrasound. Intention-to-treat analysis was implemented, and P values were adjusted by the false discovery rate method. RESULTS: At the end of the bed rest, transversus abdominis thickness was reduced by 18.3% in the inactive group (P = 0.00011) with no significant change in the RVE (-4.0%; P = 0.014 vs control) or RE (-5.0%; P = 0.10 vs control) groups. In the inactive subjects, internal oblique thickness reduced by 10.6% (P = 0.0025) and by 7% (P > 0.05) in each of the training groups. The lengthening of the lumbar spine was greatest on day 1 (+7.4%, P = 0.004) and day 2 (+6.3%, P = 0.004; day 54: +4.1%, P = 0.023). A 4.7% reduction of multifidus area was observed on day 1 of bed rest (P = 0.0049) and a 4.2% reduction of erector spinae thickness was observed on day 2 (P = 0.0011). Extensor atrophy and spinal lengthening was not affected by exercise. No significant difference was seen between RVE and RE. CONCLUSION: Bed rest leads to atrophy of the transversus abdominis and internal oblique muscles. The exercise program, which implemented lower-limb and back extension exercises against shoulder restraints, was able to reduce atrophy seen in transversus abdominis in bed rest. PMID- 27685011 TI - Evidence for Direct Transmetalation of AuIII-F with Boronic Acids. AB - The underlying reactivity of AuIII-F species with aryl boronic acids has been studied in detail taking advantage of four novel, stable difluoro-[(C^N)AuF2], arylmonofluoro-[(C^N)AuArF], and alkylmonofluoro-[(C^N)AuAlkF] gold(III) complexes, prepared and isolated in monomeric form. We provide the first experimental evidence for a direct AuIII-F/B transmetalation preceding the Csp2 Csp2 or Csp3-Csp2 bond formation. PMID- 27685012 TI - Fluorescence Activated Cell Sorting (FACS) and Gene Expression Analysis of Fos expressing Neurons from Fresh and Frozen Rat Brain Tissue. AB - The study of neuroplasticity and molecular alterations in learned behaviors is switching from the study of whole brain regions to the study of specific sets of sparsely distributed activated neurons called neuronal ensembles that mediate learned associations. Fluorescence Activated Cell Sorting (FACS) has recently been optimized for adult rat brain tissue and allowed isolation of activated neurons using antibodies against the neuronal marker NeuN and Fos protein, a marker of strongly activated neurons. Until now, Fos-expressing neurons and other cell types were isolated from fresh tissue, which entailed long processing days and allowed very limited numbers of brain samples to be assessed after lengthy and complex behavioral procedures. Here we found that yields of Fos-expressing neurons and Fos mRNA from dorsal striatum were similar between freshly dissected tissue and tissue frozen at -80 oC for 3 - 21 days. In addition, we confirmed the phenotype of the NeuN-positive and NeuN-negative sorted cells by assessing gene expression of neuronal (NeuN), astrocytic (GFAP), oligodendrocytic (Oligo2) and microgial (Iba1) markers, which indicates that frozen tissue can also be used for FACS isolation of glial cell types. Overall, it is possible to collect, dissect and freeze brain tissue for multiple FACS sessions. This maximizes the amount of data obtained from valuable animal subjects that have often undergone long and complex behavioral procedures. PMID- 27685013 TI - Knee rotationplasty: motion of the body centre of mass during walking. AB - Knee rotationplasty (KRP) is a type of surgery in which the rotated ankle serves as a new knee after being removed for bone tumor. Although this limb salvage surgery is rarely indicated in properly selected patients, it may offer functional advantages over transfemoral amputation, and more durable results compared with a prosthesis. The walking mechanics of adult patients after KRP is believed to be close to that of below-knee amputees. In this study, we evaluated steady-state walking of KRP patients from the viewpoint of the overall muscle power needed to keep the body centre of mass in motion. Three adult patients after KRP, all athletes, were evaluated. Ground reactions during walking were recorded during six subsequent strides on a force treadmill. The positive mechanical work and power sustaining the motion of the centre of mass and the recovery of muscle energy due to the pendulum-like mechanism of walking were computed and compared with those obtained in previous studies from above-knee, below-knee amputees and healthy individuals. In KRP patients, walking was sustained by a muscle power output which was 1.4-3.6 times lower during the step performed on the rotated limb than on the subsequent step. The recovery of muscle energy was slightly lower (0.9) or higher (1.3-1.4 times) on the affected side. In two out of the three KRP patients, our findings were more similar to those from above-knee amputees than to those from below-knee amputees. After KRP, the rotated limb does not necessarily provide the same power provided by below-knee amputation. This may have a relevance for the paralympic classification of KRP athletes. PMID- 27685014 TI - Notes from the Field: Measles Outbreak of Unknown Source - Shelby County, Tennessee, April-May 2016. AB - On April 15, 2016, local public health officials in Shelby County, Tennessee, were notified of a positive measles immunoglobulin M (IgM) test for a male aged 18 months (patient A). On April 18, 2016, a second positive measles IgM test was reported for a man aged 50 years (patient B). Both patients had rash onset on April 9, 2016. The Shelby County Health Department initiated an investigation, and confirmatory testing for measles virus on oropharyngeal swabs by polymerase chain reaction (PCR) at CDC was positive for both patients. On April 21, 2016, public health officials were notified of a third suspected measles case in a female aged 7 months (patient C) who had developed a rash on April 14; PCR testing was positive. Genotyping conducted at CDC identified genotype B3 measles virus in all three cases. Genotype B3 is known to be circulating globally and has previously been associated with imported cases in the United States (1). PMID- 27685015 TI - Optical Coherence Tomographic Angiography in Acute Macular Neuroretinopathy. AB - Importance: Acute macular neuroretinopathy (AMN) is a rare, yet increasingly recognized, entity identified predominantly in young healthy females with acute onset of paracentral scotomas. The exact pathophysiology is unknown but an underlying vascular process is suspected. This study used optical coherence tomographic angiography (OCTA) to assess for any evidence of vascular flow abnormality in the retina or choroid in this elusive disease. Observations: Three eyes from 2 young female patients with classic features of AMN are presented. Multimodal imaging testing, including near-infrared reflectance, spectral-domain OCT, and OCTA (Carl Zeiss Meditec), were performed. Near-infrared reflectance identified typical hyporeflective tear-drop parafoveal lesions, which corresponded to OCTA flow deficits at the level of the choriocapillaris. Conclusions and Relevance: Recognizing that these findings are based only on 3 eyes from 2 patients, lesions in AMN may result from a vascular insult in the choriocapillaris. The evaluation of OCTA was with the knowledge of the AMN diagnosis, which may have biased the interpretation. PMID- 27685016 TI - One cell model establishment to inhibit CaMKIIgamma mRNA expression in the dorsal root ganglion neuron by RNA interfere. AB - CaMKIIgamma in dorsal root ganglion neurons is closely related to the neuropathic pain, neuron injury induced by local anesthetics. To get great insight into the function of CaMKIIgamma in dorsal root ganglion neurons, we need one cell model to specially inhibit the CaMKIIgamma mRNA expression. The present study was aimed to establish one cell model to specially inhibit the CaMKIIgamma mRNA expression. We designed the CaMKIIgamma shRNA sequence and connected with pYr-1.1 plasmid. The ligation product of the CaMKIIgammashRNA and pYr-1.1 plasmid was recombined with pAd/PL-DEST vector into pAD-CaMKIIgamma-shRNA. adenovirus vector. pAD CaMKIIgamma-shRNA. adenovirus vector infected the dorsal root ganglion neuron to inhibit the CaMKIIgamma mRNA expression in vitro. The pAD-CaMKIIgamma-shRNA adenovirus vector was verified to be correct by the digestion, sequence. And pAD CaMKIIgamma-shRNA. adenovirus vector can infect the DRG cells to inhibit the CaMKIIgamma mRNA or protein expression by the real-time polymerase chain reaction (PCR) or western blotting. Those results showed that we successfully constructed one adenovirus vector that can infect the dorsal root ganglion neuron to inhibit the CaMKIIgamma mRNA and protein expression. That will supply with one cell model for the CaMKIIgamma function study. PMID- 27685017 TI - A Computational Efficient Method to Assess the Sensitivity of Finite-Element Models: An Illustration With the Hemipelvis. AB - Assessing the sensitivity of a finite-element (FE) model to uncertainties in geometric parameters and material properties is a fundamental step in understanding the reliability of model predictions. However, the computational cost of individual simulations and the large number of required models limits comprehensive quantification of model sensitivity. To quickly assess the sensitivity of an FE model, we built linear and Kriging surrogate models of an FE model of the intact hemipelvis. The percentage of the total sum of squares (%TSS) was used to determine the most influential input parameters and their possible interactions on the median, 95th percentile and maximum equivalent strains. We assessed the surrogate models by comparing their predictions to those of a full factorial design of FE simulations. The Kriging surrogate model accurately predicted all output metrics based on a training set of 30 analyses (R2 = 0.99). There was good agreement between the Kriging surrogate model and the full factorial design in determining the most influential input parameters and interactions. For the median, 95th percentile and maximum equivalent strain, the bone geometry (60%, 52%, and 76%, respectively) was the most influential input parameter. The interactions between bone geometry and cancellous bone modulus (13%) and bone geometry and cortical bone thickness (7%) were also influential terms on the output metrics. This study demonstrates a method with a low time and computational cost to quantify the sensitivity of an FE model. It can be applied to FE models in computational orthopaedic biomechanics in order to understand the reliability of predictions. PMID- 27685019 TI - Confidence in forced-choice recognition: What underlies the ratings? AB - Two-alternative forced-choice recognition tests are commonly used to assess recognition accuracy that is uncontaminated by changes in bias. In such tests, participants are asked to endorse the studied item out of 2 presented alternatives. Participants may be further asked to provide confidence judgments for their recognition decisions. It is often assumed that both recognition decisions and confidence judgments in 2-alternative forced-choice recognition tests depend on participants' assessments of a difference in strength of memory evidence supporting the 2 alternatives-the relative account. In the present study we focus on the basis of confidence judgments and we assess the relative account of confidence against the absolute account of confidence, by which in assigning confidence participants consider only strength of memory evidence supporting the chosen alternative. The results of the study show that confidence in 2 alternative forced-choice recognition decisions is higher when memory evidence is stronger for the chosen alternative and also when memory evidence is stronger for the unchosen alternative. These patterns of results are consistent with the absolute account of confidence in 2-alternative forced-choice recognition but they are inconsistent with the relative account. (PsycINFO Database Record PMID- 27685018 TI - The role of long-term memory in a test of visual working memory: Proactive facilitation but no proactive interference. AB - We report 4 experiments examining whether associations in visual working memory are subject to proactive interference from long-term memory (LTM). Following a long-term learning phase in which participants learned the colors of 120 unique objects, a working memory (WM) test was administered in which participants recalled the precise colors of 3 concrete objects in an array. Each array in the WM test consisted of 1 old (previously learned) object with a new color (old mismatch), 1 old object with its old color (old-match), and 1 new object. Experiments 1 to 3 showed that WM performance was better in the old-match condition than in the new condition, reflecting a beneficial contribution from LTM. In the old-mismatch condition, participants sometimes reported colors associated with the relevant shape in LTM, but the probability of successful recall was equivalent to that in the new condition. Thus, information from LTM only intruded in the absence of reportable information in WM. Experiment 4 tested for, and failed to find, proactive interference from the preceding trial in the WM test: Performance in the old-mismatch condition, presenting an object from the preceding trial with a new color, was equal to performance with new objects. Experiment 5 showed that long-term memory for object-color associations is subject to proactive interference. We conclude that the exchange of information between LTM and WM appears to be controlled by a gating mechanism that protects the contents of WM from proactive interference but admits LTM information when it is useful. (PsycINFO Database Record PMID- 27685021 TI - Orthographic neighborhood effects in recognition and recall tasks in a transparent orthography. AB - The number of orthographic neighbors of a word influences its probability of being retrieved in recognition and free recall memory tests. Even though this phenomenon is well demonstrated for English words, it has yet to be demonstrated for languages with more predictable grapheme-phoneme mappings than English. To address this issue, 4 experiments were conducted to investigate effects of number of orthographic neighbors (N) and effects of frequency of occurrence of orthographic neighbors (NF) on memory retrieval of Brazilian Portuguese words. One hundred twenty-four Brazilian Portuguese speakers performed first a lexical decision task (LDT) on words that were factorially manipulated according to N and NF, and intermixed with either nonpronounceable nonwords without orthographic neighbors (Experiments 1A and 2A), or with pronounceable nonwords with a large number of orthographic neighbors (Experiments 1B and 2B). The words were later used as probes on either recognition (Experiments 1A and 1B) or recall tests (Experiments 2A and 2B). Words with 1 orthographic neighbor were consistently better remembered than words with several orthographic neighbors in all recognition and recall tests. Notably, whereas in Experiment 1A higher false alarm rates were yielded for words with several rather than 1 orthographic neighbor, in Experiment 1B higher false alarm rates were yielded for words with 1 rather than several orthographic neighbors. Effects of NF, on the other hand, were not consistent among memory tasks. The effects of N on the recognition and recall tests conducted here are interpreted in light of dual process models of recognition. (PsycINFO Database Record PMID- 27685020 TI - The effect of semantic transparency on the processing of morphologically derived words: Evidence from decision latencies and event-related potentials. AB - Decomposition theories of morphological processing in visual word recognition posit an early morpho-orthographic parser that is blind to semantic information, whereas parallel distributed processing (PDP) theories assume that the transparency of orthographic-semantic relationships influences processing from the beginning. To test these alternatives, the performance of participants on transparent (foolish), quasi-transparent (bookish), opaque (vanish), and orthographic control words (bucket) was examined in a series of 5 experiments. In Experiments 1-3 variants of a masked priming lexical-decision task were used; Experiment 4 used a masked priming semantic decision task, and Experiment 5 used a single-word (nonpriming) semantic decision task with a color-boundary manipulation. In addition to the behavioral data, event-related potential (ERP) data were collected in Experiments 1, 2, 4, and 5. Across all experiments, we observed a graded effect of semantic transparency in behavioral and ERP data, with the largest effect for semantically transparent words, the next largest for quasi-transparent words, and the smallest for opaque words. The results are discussed in terms of decomposition versus PDP approaches to morphological processing. (PsycINFO Database Record PMID- 27685023 TI - Conflict and bias in heuristic judgment. AB - Conflict has been hypothesized to play a key role in recruiting deliberative processing in reasoning and judgment tasks. This claim suggests that changing the task so as to add incorrect heuristic responses that conflict with existing heuristic responses can make individuals less likely to respond heuristically and can increase response accuracy. We tested this prediction in experiments involving judgments of argument strength and word frequency, and found that participants are more likely to avoid heuristic bias and respond correctly in settings with 2 incorrect heuristic response options compared with similar settings with only 1 heuristic response option. Our results provide strong evidence for conflict as a mechanism influencing the interaction between heuristic and deliberative thought, and illustrate how accuracy can be increased through simple changes to the response sets offered to participants. (PsycINFO Database Record PMID- 27685022 TI - Looking inward and back: Real-time monitoring of visual working memories. AB - Confidence in our memories is influenced by many factors, including beliefs about the perceptibility or memorability of certain kinds of objects and events, as well as knowledge about our skill sets, habits, and experiences. Notoriously, our knowledge and beliefs about memory can lead us astray, causing us to be overly confident in eyewitness testimony or to overestimate the frequency of recent experiences. Here, using visual working memory as a case study, we stripped away all these potentially misleading cues, requiring observers to make confidence judgments by directly assessing the quality of their memory representations. We show that individuals can monitor the status of information in working memory as it degrades over time. Our findings suggest that people have access to information reflecting the existence and quality of their working memories, and furthermore, that they can use this information to guide their behavior. (PsycINFO Database Record PMID- 27685024 TI - The use of echocardiography for the non-invasive evaluation of coronary artery disease. AB - In the Western world, there are now millions of patients who undergo clinical procedures that evaluate coronary artery status each year. Methods span from direct imaging using angiography, computerized tomography, to nuclear magnetic imaging as well as to functional studies, such as positron emission tomography. These techniques have provided significant information to physicians, but there is still need for an improved accessibility. Angiographic methods are expensive and expose the patient to significant amounts of radiation, undesirable in younger patients. Among the novel technologies for coronary diagnostics, transthoracic echocardiography (TTE) of coronary arteries has provided an important alternative, particularly in everyday practice. Diagnostic arterial TTE can allow determination of the coronary wall lumen in at least three major coronary segments (left main [LM], left arterial descending [LAD] and right coronary artery [RCA]). Coronary wall thickness using the LAD has been preliminarily shown to be related to the risk of coronary events. Since it is well ascertained that coronary lesions found in any location indicate that at least 80% of the coronary tree is affected, this is very important clinical information. Evaluation of coronary status by TTE is a novel technology providing important information in ischemic syndromes, in cases of coronary malformations and other coronary diseases. KEY MESSAGES Coronary evaluation can be carried out by a variety of both invasive and non-invasive methods, many requiring radiation exposure or patient immobility. Transthoracic echocardiography (TTE) of the coronaries can, in particular, evaluate the coronary wall thickness, and this may be directly related to the coronary disease risk. TTE is a useful method for the monitoring of coronary flow reserve and can allow the detection of coronary malformations. PMID- 27685025 TI - ALSUntangled No. 36: Accilion. PMID- 27685026 TI - Small at Birth, but How Small? The Definition of SGA Revisited. PMID- 27685027 TI - Pharmacoepigenetics of the role of DNA methylation in MU-opioid receptor expression in different human brain regions. AB - AIM: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of MU-opioid receptor expression across the brain. METHODS: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, MU-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein. RESULTS & CONCLUSION: While high or low MU opioid receptor expression significantly correlated with local OPRM1 mRNA levels, there was no corresponding association with OPRM1 methylation status. Additional experiments in human cell lines showed that changes in DNA methylation associated with changes in MU-opioid expression were an order of magnitude greater than differences in brain. Hence, different degrees of DNA methylation associated with chronic opioid exposure are unlikely to exert a major role in the region specificity of MU-opioid receptor expression in the human brain. PMID- 27685028 TI - The experience of transitioning from relapsing remitting to secondary progressive multiple sclerosis: views of patients and health professionals. AB - PURPOSE: The majority of people with multiple sclerosis (pwMS) initially present with discreet periods of relapses followed by partial remission of symptoms (RRMS). Over time, most pwMS transition to secondary progressive MS (SPMS), characterized by a gradual accumulation of disability. This study aimed to explore the experiences, coping and needs associated with transitioning from RRMS to SPMS. METHOD: Data were collected via semi-structured interviews with nine pwMS and seven specialist MS health professionals (HPs). Thematic analysis was used to analyze the data. RESULTS: Four major themes were identified: "Is this really happening?"; "Becoming a reality"; "A life of struggle"; and "Brushing oneself off and moving on." Findings suggested a process of moving from uncertainty towards confirmation of one's diagnostic label. Being reclassified with SPMS served as a turning point for many, and was accompanied by a range of cognitive, emotional and behavioral responses. The value of adequate information and support surrounding the transition, and the potential benefit of education and support for health professionals in relation to the transition were indicated. CONCLUSIONS: Understanding pwMS' experiences of the transition is essential if clinicians are to provide pwMS with appropriate support during the transition. Implications for Rehabilitation The timing and delivery of preparatory education for patients about the transition to SPMS should be carefully considered. Sufficient information and follow-up support following the reclassification of SPMS is crucial but sometimes lacking. The importance of sensitive communication of the reclassification of SPMS was highlighted. MS Specialist health professionals may potentially benefit from training and support around communication of the reclassification of SPMS. Given the potential negative psychological impact of the transition, the psychological wellbeing of the patients during the transition to SPMS should be monitored and responded to appropriately. PMID- 27685030 TI - UV-B radiation reduces in vitro germination of Metarhizium anisopliae s.l. but does not affect virulence in fungus-treated Aedes aegypti adults and development on dead mosquitoes. AB - AIMS: Control of diurnal Aedes aegypti with mycoinsecticides should consider the exposure of fungus-treated adults to sunlight, and especially to UV-B radiation that might affect activity of conidia applied on the mosquito's surface. METHODS AND RESULTS: Germination of Metarhizium anisopliae s.l. IP 46 conidia on SDAY medium was not affected at the lowest level of radiation with UV-B, 0.69 kJ m-2 , but was retarded and reduced at higher 2.075 and 4.15 kJ m-2 , and completely inhibited at >=8.3 kJ m-2 . In contrast, germination of conidia applied onto fibreglass nettings and exposed from 0 to 16.6 kJ m-2 did not differ significantly among levels of irradiance exposure and the controls. There was also no significant impact of UV-B up to 16.6 kJ m-2 on the adulticidal activity of IP 46 and on the subsequent conidiogenesis on cadavers. The Quaite-weighted UV B irradiance in the laboratory (1152 mW m-2 ) was higher than the natural sunlight irradiance observed in the city of Goiania in Central Brazil on midday (706 mW m-2 in August to 911 mW m-2 in October 2015). CONCLUSIONS: UV-B does not impair the activity of IP 46 conidia applied previously to radiation on A. aegypti adults. SIGNIFICANCE AND IMPACT OF THE STUDY: Findings contribute to a better understanding of the effectiveness of M. anisopliae against day-active A. aegypti and its potential for biological mosquito control. PMID- 27685033 TI - 'It is the systems imposed on trusts rather than the people who are to blame for the inefficiencies'. AB - News that health secretary Stephen Dorrell has pledged to reduce NHS bureaucracy is welcome, albeit that it is an extraordinary about turn for the government. Long forgotten presumably is the fact that the increase in administration and paperwork was as a direct result of the NHS reforms. But better later than never. PMID- 27685032 TI - Polyethyleneimine-Coated Gold Nanoparticles: Straightforward Preparation of Efficient DNA Delivery Nanocarriers. AB - A novel one-pot method for the synthesis of polyethyleneimine (PEI)-coated gold nanoparticles (AuPEI-NPs) that combines the reductant-stabilizer properties of PEI with microwave irradiation starting from hydrogen tetrachloroaurate acid (HAuCl4 ) and branched PEI 25 kDa (b25kPEI) was explored. The method was straightforward, green, and low costing, for which the Au/PEI ratio (1:1 to 1:128 w/w) was a key parameter to modulate their capabilities as DNA delivery nanocarriers. Transfection assays in CHO-k1 cells demonstrated that AuPEI-NPs with 1:16 and 1:32 w/w ratios behaved as effective DNA gene vectors with improved transfection efficiencies (twofold) and significantly lower toxicity than unmodified b25kPEI and Lipofectamine 2000. The transfection mediated by these AuPEI-NP-DNA polyplexes preferentially used the caveolae-mediated route for intracellular internalization, as shown by studies performed by using specific internalization inhibitors as well as colocalization with markers of clathrin- and caveolae-dependent pathways. The AuPEI-NP polyplexes preferentially used the more efficient caveolae internalization pathway to promote transfection, a fact that supports their higher transfection efficiency relative to that of Lipofectamine 2000. In addition, intracellular trafficking of the AuPEI-NPs was studied by transmission electron microscopy. PMID- 27685035 TI - ? AB - Royal London hospital nurses Nicola Eccersley, left, and Cathy Green laid a wreath List week at the statue of nurse Edith Cavell to mark the 80th anniversary' of her death. She was executed in 1915 after helping allied troops escape from occupied Belgium during World War 1. PMID- 27685034 TI - Unions seem certain to accept pay deal. AB - The nurses' pay dispute seems certain to be resolved next week after Unison members voted in favour of a framework agreement which will allow trusts to negotiate local deals this year. PMID- 27685036 TI - RCN members will be asked to approve rise in subscriptions. AB - Royal College of Nursing members will be asked to approve a L3.50 increase in subscriptions for 1996 at the RCN's annual general meeting in Edinburgh today. PMID- 27685038 TI - Theatre nurses congress told timing of consent from patients is important. AB - Asking patients to consent to treatment weeks before they undergo surgery could present problems if their minds or circumstances change in the period between the granting of consent and their operation, the National Association of Theatre Nurses' (NATN) annual congress heard. PMID- 27685039 TI - Inferiority complex is stopping nurse managers developing a strategic role. AB - Nurse managers undersell their abilities because they are more concerned with just doing the job, a report from the King's Fund has found. PMID- 27685040 TI - Doctors receive guidance on being polite to patients. AB - Doctors have been told they must be polite to patients and respect their opinions under new guidelines published last week by their regulatory body, the General Medical Council. PMID- 27685041 TI - Call for inquiry into 'spread of freemasonry' in nursing. AB - One of the contestants in this week's election for the chair of the RCN Council has written to fellow council members following revelations that he is a freemason. PMID- 27685042 TI - Award to help health authorities become crystal clear. AB - The Plain English Campaign is set to launch a new award to encourage health authorities to stop talking and writing in impenetrable jargon and gobbledygook. PMID- 27685044 TI - Hancock tells Dorrell nurses should be on new boards. AB - RCN general secretary Christine Hancock left health secretary Stephen Dorrell in no doubt at nurses' anger over their widespread exclusion from the new health authorities when the two met at a conference fringe meeting. PMID- 27685043 TI - External chair for inquiry into death of baby Ryan. AB - An external chair has been appointed to direct the inquiry into the circumstances surrounding the death of baby Ryan Smith, aged 11 months. The chair will select a GP and a senior nurse to join the inquiry. PMID- 27685045 TI - Cautious welcome for plans to reduce NHS bureaucracy. AB - Government attempts to cut bureaucracy in the health service must reduce the burden on nurses and other clinical staff, the Royal College of Nursing has insisted. PMID- 27685046 TI - Health secretary unrecognised but still disliked. AB - Only one in twelve voters recognise health secretary, Stephen Dorrell and most people think he's a liability to the government, a Gallup poll for the Daily Telegraph found. PMID- 27685047 TI - Delegate says community care is failing her dying son. AB - Health secretary Stephen Dorrell has asked an anxious mother for details of how community care has failed to provide adequate cover for her son who is dying of motor neurone disease. PMID- 27685049 TI - Thousands of nurses sacked as turmoil over pay continues in South Africa. AB - At least 7,000 nurses have been sacked for going on strike in the Eastern Cape as turmoil grows over pay in South Africa. PMID- 27685048 TI - Health service staff support French public sector strike. AB - French nurses supported the public sector strike which brought the country to a standstill last week, but few actually took action. PMID- 27685050 TI - Swedish midwife begins legal fight over right to equal pay. AB - A Swedish midwife who believes she would earn more if she were a man could be about to make legal history in her quest for a better salary. PMID- 27685052 TI - Neonatal nurses and medication workload. AB - A significant amount of neonatal nurses' time is spent on medication-related activities which might in part be undertaken by a pharmacy service. PMID- 27685051 TI - Criticism as European drive to fight cancer makes no mention of nurses. AB - A nurse has criticised a new European campaign to fight cancer because it makes no mention of nurses. PMID- 27685053 TI - Cirrhosis deaths cut by urgent drugs. AB - Early administration of terlipressin plus glyceryl trinitrate to people with gastrointestinal bleeding associated with cirrhosis reduces mortality, French researchers report. PMID- 27685055 TI - Detecting tuberculosis from the breath. AB - A device which can detect Mycobacterium tuberculosis in breath is under development in America. PMID- 27685054 TI - Serious MRSA infection in the community. AB - Serious methicillin-resistant Staphylococcus aureus (MRSA) infection might occur outside hospitals, following acquisition in the community and patients misusing drugs might be at increased risk. PMID- 27685056 TI - ? AB - Normal toileting is not simply a matter of learning to respond to bladder and bowel pressures by relaxing, but rather is a complex operant and social learning process that has been hindered by a reduced learning capacity and by institutionalisation ( 1 ). PMID- 27685057 TI - Coming up roses for ENs in wales. AB - After reading the article about Rose McLoughlin 'An EN by any other name....' (News August 30) I realise how fortunate we are in Wales for the recognition given to the value of ENs. PMID- 27685058 TI - Nurses' promotion project is a big hit with shoppers. AB - The slogan 'The menopause: be aware you can prepare' was used on a recent health promotion campaign when five student nurses from the University of Portsmouth went to Cascades Shopping Centre in Portsmouth to give help and advice to women on the menopause. PMID- 27685060 TI - Some celebrities more apt than others. AB - With regard to Emily Biggins letter 'Football stars a welcome sight for health promotion', (Viewpoint Letters) I do get Emily's drift about the good celebrities can do in promoting health, but surely some are more fit for the job than others. I mean how healthy is a kung fu kick to the head? PMID- 27685059 TI - Health visitors find success on abuse. AB - Having read the excellent article (Clinical September 13) about 'Helping adults cope with abuse as children' by Janet Jones, psychological therapist, we would like to inform you about a similar programme we have been involved with over the last years in Somerset. PMID- 27685061 TI - Labour right about ungagging NHS staff. AB - I was pleased to see Labour plans to scrap the' gagging clause in NHS staff contracts (News October 1). PMID- 27685062 TI - Inclined to agree with tabloid opinions. AB - 'Bring back real nurses' read the Daily Mail headline on its letters page. Sadly nursing has changed. PMID- 27685063 TI - Once bitten, twice shy of some A&Es. AB - After suffering a dog bite I attended the A&E department of my local teaching hospital. PMID- 27685064 TI - One minute wisdom. AB - During a recent holiday in America I was invited to a local 'health fair'. Curious about what to expect took my family along. PMID- 27685065 TI - Information exchange. AB - We are trying to arrange a 20-year nurses' reunion. The group commenced nursing in September 1976 at the Royal Liverpool Hospital College. PMID- 27685067 TI - Student of the year winner. AB - Susan Berwick is the winner of this year's ANS/Nursing Standardstudent nurse of the year award. PMID- 27685066 TI - Editorial. AB - Having been practising now for a year, I realise nursing in the real world can be a tough proposition. PMID- 27685069 TI - Testicular cancer campaign promotes self examination. AB - The Department of Health is running a new campaign to encourage testicular self examination among young men, aimed in particular at schools and colleges. PMID- 27685068 TI - Scottish student is youngest Lib Dem councillor. AB - Claire Hamblen, 21, a student nurse and Scotland's youngest local Liberal Democrat councillor, was recently featured in Cosmopolitan magazine. PMID- 27685070 TI - Drink campaign targets students. AB - A student alcohol awareness campaign was launched last month to raise awareness of the harm excess alcohol can cause. PMID- 27685073 TI - Students left with no supervision. AB - The increased use of bank and agency staff combined with the growth of short-term contracts are endangering the quality of clinical supervision on wards. PMID- 27685072 TI - Stress survival guide. AB - A survival guide aimed at helping students cope with the stress of student life is now available from the mental health charity MIND. PMID- 27685071 TI - Rent rise rooms in poor condition. AB - Student nurses at Guy's Hospital in London arc living in appalling conditions despite rents having risen from L50 to L151, a nurse has claimed. PMID- 27685074 TI - Sabbatical officer to urge students to 'get involved'. AB - Erica Forth, sabbatical student officer for the north of England will be encouraging nurse students to get involved in the life and organisation of their colleges. PMID- 27685075 TI - Reed to promote constructive criticism of college courses. AB - 'Get motivated,' says jenni Reed, ANS sabbatical officer responsible for encouraging RCN recruitment and organisation in the south. She wants to increase membership of the college believing it has a great deal to offer students. PMID- 27685076 TI - On a bursary so I can't get a loan. AB - I am a student nurse starting my branch programme at Christ Church College, Canterbury. PMID- 27685078 TI - Listing. PMID- 27685077 TI - Am the only lesbian nurse? AB - Prior to entering nursing I encountered many nurses who were lesbians. Now that I am here I can hear closet doors slamming all around me. PMID- 27685079 TI - Attachment to God, religious tradition, and firm attributes in workplace commitment. AB - Research on organizational commitment suggests there is an association between American theists' emotional attachment to God and their emotional commitment to the workplace. A sense of divine calling has been shown to partially mediate this association but, beyond that, little is known. The purpose of this study is to shed further light on the relationship between secure attachment to God and affective organizational commitment. I do so by testing whether the employee's religious tradition is associated with affective organizational commitment and whether the employee's firm attributes moderate the relationship between attachment to God and organizational commitment. Results suggest that: 1) Catholics evince higher levels of organizational commitment than Evangelicals, and 2) firm size significantly moderates the relationship between attachment to God and organizational commitment across religious affiliations. PMID- 27685080 TI - Communication between patients with obstructive sleep apnoea syndrome and healthcare personnel during the initial visit to a continuous positive airway pressure clinic. AB - AIMS AND OBJECTIVES: To describe facilitators and barriers from a patient perspective in communications between patients with obstructive sleep apnoea syndrome and healthcare personnel during the first meeting when continuous positive airway pressure is initiated. BACKGROUND: Adherence to continuous positive airway pressure treatment tends to be poor, especially at the initial phase of treatment. Communication between the patient and healthcare personnel has not been studied from the patient perspective, as either a barrier or facilitator for adherence. METHODS: A descriptive design using qualitative content analysis was used. Interviews with 25 patients with obstructive sleep apnoea syndrome took place after their initial visit at four continuous positive airway pressure clinics. A deductive analysis based on The 4 Habits Model (i.e. emphasise the importance of investing in the beginning of the consultation, elicit the patient's perspective, demonstrate empathy and invest in the end of the consultation) was conducted. RESULTS: Building confidence (i.e. structure building, information transfer, commitment) or hindering confidence (i.e. organisational insufficiency, stress behaviour, interaction deficit) was associated with investing in the beginning. Motivating (i.e. situational insight, knowledge transfer, practical training) or demotivating (i.e. expectations, dominance and power asymmetry, barriers) was associated with eliciting the patient's perspective. Building hope (i.e. awareness, sensitivity, demonstration of understanding) or hindering hope (i.e. unprepared, uncommitted, incomprehension) was associated with showing empathy. Agreement (i.e. confirmation, responsibilities, comprehensive information) or disagreement (i.e. structural obscurity, irresponsibility, absent-mindedness) was associated with investing in the end. CONCLUSIONS: Understanding of facilitators and barriers, as described by patients, can be used to improve contextual conditions and communication skills among healthcare personnel. RELEVANCE TO CLINICAL PRACTICE: A patient-centred communication technique should be used in relation to all stages of The 4 Habits Model to facilitate shared decision-making and improve adherence to continuous positive airway pressure treatment. PMID- 27685081 TI - Management of Major Bleeding Related to Novel Oral Anticoagulant Agents Use in Frail Elderly Adults. PMID- 27685082 TI - Chemical Composition and Allelopathic Potential of Essential Oils from Citharexylum spinosum L. Grown in Tunisia. AB - Citharexylum spinosum L. (Verbenaceae) also known as Citharexylum quadrangulare Jacq. or Citharexylum fruticosum L. is an exotic tree introduced many years ago in Tunisia, specially used as a street and park ornamental tree. Essential oils (EOs) were obtained by hydrodistillation of the different parts (roots, stems, leaves, flowers and fruits; drupes) collected from trees grown in the area of Monastir (Tunisia). In total, 84 compounds, representing 90.1 - 98.4% of the whole oil composition, were identified by GC-FID and GC/MS analyses. The root EO was distinguished by its high content in monoterpene hydrocarbons (alpha phellandrene; 30.8%) whereas that obtained from stems was dominated by sesquiterpene hydrocarbons (cuparene; 16.4%). The leaf oil was rich in an apocarotenoid derivative (hexahydrofarnesylacetone; 26%) and an aliphatic hydrocarbon (nonadecane; 14.5%). Flowers oil was rich in esters (2-phenylethyl benzoate; 33.5%). Finally, drupes oil was rich in oxygenated sesquiterpenes (beta eudesmol; 33.1%). Flowers oil showed a significant phytotoxic effect against lettuce seeds germination, it induces a total inhibition when tested at 1 mg/ml. Root and shoot elongation seemed to be more affected than germination. The inhibition of the shoot length varied from 3.6% to 100% and that of the root from 16.1% to 100%. The highest inhibition of 100% was detected for flower oil tested at 1 mg/ml. Our in vitro studies suggest a possible and new alternative use of C. spinosum EOs in herbicidal formulations, further experiments involving field conditions are necessary to confirm its herbicidal potential. PMID- 27685083 TI - Beyond love: a qualitative analysis of factors associated with teenage pregnancy among young women with pregnancy experience in Bolgatanga, Ghana. AB - Globally, an estimated 16 million young women aged 15 to 19 years give birth every year. Most teenage pregnancies are unintended and being pregnant or delivering a baby as a teenager can have serious adverse consequences. Knowledge of the environmental factors and social cognitive determinants influencing young women's failure to protect against unintended pregnancy is necessary to address the high rate of teenage pregnancies. We conducted semi-structured in-depth interviews with 21 young women, who had experience of pregnancy, in Bolgatanga, Ghana. The interview protocol included themes (relationships, sex, pregnancy, family planning) and determinants (knowledge, attitudes, self-efficacy, norms, risk perceptions) derived from empirical studies and theories related to sexuality behaviour. Findings show that young women's motivations for sexual relationships are mostly 'beyond love' and seem to focus on economic factors. The main means of sexual protection seems to be condom use. Other forms of contraception were believed to be linked to infertility. Sexuality remains a largely taboo topic for open discussion and sex education in schools seems limited to abstinence-only messages. The need for more open communication on matters of sexuality with young people and the provision of a more comprehensive sexuality education in school to address teenage pregnancies in Ghana, is discussed. PMID- 27685084 TI - Influence of pH on the structure and stability of the sweet protein MNEI. AB - MNEI is a single-chain derivative of the sweet protein monellin that, in recent years, has become an accepted model for studying protein dynamic properties such as folding and aggregation. Although MNEI is very resistant at acidic pH, exposure to neutral or alkaline pH strongly affects its stability. We have performed a thorough NMR study of the dynamic properties of MNEI at different pHs. The results demonstrate that, at physiological temperature, exposure to higher pH increases MNEI flexibility. The changes, originating from a well defined region in the protein, are transmitted to the whole structure and are likely to be the key for triggering unfolding processes. PMID- 27685085 TI - Pseudoangiomatous Xanthelasmoid Mastocytosis - a new histopathological entity. PMID- 27685086 TI - Fungal Super Glue: The Biofilm Matrix and Its Composition, Assembly, and Functions. PMID- 27685087 TI - Quantitative Expression Analysis in Brassica napus by Northern Blot Analysis and Reverse Transcription-Quantitative PCR in a Complex Experimental Setting. AB - Analysis of gene expression is one of the major ways to better understand plant reactions to changes in environmental conditions. The comparison of many different factors influencing plant growth challenges the gene expression analysis for specific gene-targeted experiments, especially with regard to the choice of suitable reference genes. The aim of this study is to compare expression results obtained by Northern blot, semi-quantitative PCR and RT-qPCR, and to identify a reliable set of reference genes for oilseed rape (Brassica napus L.) suitable for comparing gene expression under complex experimental conditions. We investigated the influence of several factors such as sulfur deficiency, different time points during the day, varying light conditions, and their interaction on gene expression in oilseed rape plants. The expression of selected reference genes was indeed influenced under these conditions in different ways. Therefore, a recently developed algorithm, called GrayNorm, was applied to validate a set of reference genes for normalizing results obtained by Northern blot analysis. After careful comparison of the three methods mentioned above, Northern blot analysis seems to be a reliable and cost-effective alternative for gene expression analysis under a complex growth regime. For using this method in a quantitative way a number of references was validated revealing that for our experiment a set of three references provides an appropriate normalization. Semi-quantitative PCR was prone to many handling errors and difficult to control while RT-qPCR was very sensitive to expression fluctuations of the reference genes. PMID- 27685088 TI - Pneumococcal Serotypes Colonise the Nasopharynx in Children at Different Densities. AB - Prevalence of pneumococcal serotypes in carriage and disease has been described but absolute serotype colonisation densities have not been reported. 515 paediatric nasal swab DNA extracts were subjected to lytA qPCR and molecular serotyping by microarray. Absolute serotype densities were derived from total pneumococcal density (qPCR cycle threshold and standard curve) and relative abundance (microarray) and varied widely. Compared to all serotype densities observed, the strongest evidence of differences was seen for serotypes 21 and 35B (higher) and 3, 38 and non-typeables (lower) (p<0.05) with a similar hierarchy when only a single serotype carriage was assessed. There was no evidence of any overall density differences between children with single or multiple serotypes detected but serotypes with mid-range densities were more prevalent. The hierarchy of distinct pneumococcal serotype carriage densities described here for the first time, may help explain the dynamics of transmission between children. PMID- 27685089 TI - Effects of low-frequency pulsed electromagnetic fields on plateau frostbite healing in rats. AB - Plateau frostbite (PF) treatments have remained a clinical challenge because this condition injures tissues in deep layers and affected tissues exhibit unique pathological characteristics. For instance, low-frequency pulsed electromagnetic field (PEMF) can affect tissue restoration and penetrate tissues. Therefore, the effect of PEMF on PF healing should be investigated. This study aimed to evaluate the effects of low-frequency PEMF on PF healing systematically. Ninety-six Sprague-Dawley rats were randomly and equally divided into three groups: normal control, partial thickness plateau frostbite (PTPF), and PTPF with low-frequency PEMF exposure (PTPF + PEMF). PTPF wounds were induced in the dorsum of the rats. The PTPF + PEMF group was exposed to low-frequency PEMF daily. During PF healing, wound microcirculation in each group was monitored through contrast ultrasonography. Wound appearance, histological observation, and wound tensile strength were also evaluated. Results showed that the rate of the microcirculation restoration of the PTPF + PEMF group was nearly 25% faster than that of the PTPF group, and wound appearance suggested that the healing of the PTPF group was slower than that of the PTPF + PEMF group. Histological observation revealed that PEMF accelerated the growth of different deep tissues, as confirmed by tensile strength examination. Low-frequency PEMF could penetrate PF tissues, promote their restoration, and provide a beneficial effect on PF healing. Therefore, this technique may be a potential alternative to treat PF. PMID- 27685090 TI - Comparative proteome profiling of bleomycin-induced lung toxicity in rats by 2D nano-LC-MS/MS and spectral counting. AB - The mechanisms involved in bleomycin-induced lung toxicity have not been fully understood to date. This work aimed to compare the proteome profiling of bleomycin-induced lung toxicity by using 2D-nano-LC-MS/MS and spectral counting. By comparing the spectral counts of identified proteins between control and bleomycin-treated groups, we noted that 102 proteins were upregulated and 28 proteins were downregulated in the bleomycin-treated group. Among these differently expressed proteins, five proteins were chosen for validation by Western blot analysis. The levels of these five proteins were consistent with proteomic results. These potential mediators can facilitate the translation of the underlying mechanisms of bleomycin-induced lung toxicity to molecular targets in the clinical arena. PMID- 27685092 TI - Comparative Metagenomics Reveal Phylum Level Temporal and Spatial Changes in Mycobiome of Belowground Parts of Crocus sativus. AB - Plant-fungal associations have been explored by routine cultivation based approaches and cultivation based approaches cannot catalogue more than 5% of fungal diversity associated with any niche. In the present study, an attempt has been made to catalogue fungal diversity associated with belowground parts i.e. rhizosphere and cormosphere, of Crocus sativus (an economically important herb) during two growth stages, using cultivation independent ITS gene targeted approach, taking bulk soil as reference. The 454 pyrosequencing sequence data analysis suggests that the fungal diversity was niche and growth stage specific. Fungi diversity, in the present case, was not only different between the two organs (roots and corm) but the dominance pattern varies between the cormosphere during two growth stages. Zygomycota was dominant fungal phylum in the rhizosphere whereas Basidiomycota was dominant in cormosphere during flowering stage. However in cormosphere though Basidiomycota was dominant phylum during flowering stage but Zygomycota was dominant during dormant stage. Interestingly, in cormosphere, the phyla which was dominant at dormant stage was rare at flowering stage and vice-versa (Basidiomycota: Flowering = 93.2% Dormant = 0.05% and Zygomycota: Flowering = 0.8% Dormant = 99.7%). At genus level, Rhizopus was dominant in dormant stage but was rare in flowering stage (Rhizopus: Dormant = 99.7% Flowering = 0.55%). This dynamics is not followed by the bulk soil fungi which was dominated by Ascomycota during both stages under study. The genus Fusarium, whose species F. oxysporum causes corm rot in C. sativus, was present during both stages with slightly higher abundance in roots. Interestingly, the abundance of Rhizopus varied a great deal in two stages in cormosphere but the abundance of Fusarium was comparable in two growth stages (Bulk soil Flowering = 0.05%, Rhizosphere Flowering = 1.4%, Cormosphere Flowering = 0.06%, Bulk soil Dormant = 2.47% and cormosphere dormant = 0.05%). This is the first report on the fungal diversity associated with the root of Crocus sativus and first report on the fungi associated with corm of any plant with the temporal and spatial variation in the fungal community structure. PMID- 27685091 TI - NUCLEAR FACTOR Y, Subunit C (NF-YC) Transcription Factors Are Positive Regulators of Photomorphogenesis in Arabidopsis thaliana. AB - Recent reports suggest that NF-Y transcription factors are positive regulators of skotomorphogenesis in Arabidopsis thaliana. Three NF-YC genes (NF-YC3, NF-YC4, and NF-YC9) are known to have overlapping functions in photoperiod dependent flowering and previous studies demonstrated that they interact with basic leucine zipper (bZIP) transcription factors. This included ELONGATED HYPOCOTYL 5 (HY5), which has well-demonstrated roles in photomorphogenesis. Similar to hy5 mutants, we report that nf-yc3 nf-yc4 nf-yc9 triple mutants failed to inhibit hypocotyl elongation in all tested light wavelengths. Surprisingly, nf-yc3 nf-yc4 nf-yc9 hy5 mutants had synergistic defects in light perception, suggesting that NF-Ys represent a parallel light signaling pathway. As with other photomorphogenic transcription factors, nf-yc3 nf-yc4 nf-yc9 triple mutants also partially suppressed the short hypocotyl and dwarf rosette phenotypes of CONSTITUTIVE PHOTOMORPHOGENIC 1 (cop1) mutants. Thus, our data strongly suggest that NF-Y transcription factors have important roles as positive regulators of photomorphogenesis, and in conjunction with other recent reports, implies that the NF-Y are multifaceted regulators of early seedling development. PMID- 27685093 TI - Oral Cooling and Carbonation Increase the Perception of Drinking and Thirst Quenching in Thirsty Adults. AB - Fluid ingestion is necessary for life, and thirst sensations are a prime motivator to drink. There is evidence of the influence of oropharyngeal stimulation on thirst and water intake in both animals and humans, but how those oral sensory cues impact thirst and ultimately the amount of liquid ingested is not well understood. We investigated which sensory trait(s) of a beverage influence the thirst quenching efficacy of ingested liquids and the perceived amount ingested. We deprived healthy individuals of liquid and food overnight (> 12 hours) to make them thirsty. After asking them to drink a fixed volume (400 mL) of an experimental beverage presenting one or two specific sensory traits, we determined the volume ingested of additional plain, 'still', room temperature water to assess their residual thirst and, by extension, the thirst-quenching properties of the experimental beverage. In a second study, participants were asked to drink the experimental beverages from an opaque container through a straw and estimate the volume ingested. We found that among several oro-sensory traits, the perceptions of coldness, induced either by cold water (thermally) or by l-menthol (chemically), and the feeling of oral carbonation, strongly enhance the thirst quenching properties of a beverage in water-deprived humans (additional water intake after the 400 ml experimental beverage was reduced by up to 50%). When blinded to the volume of liquid consumed, individual's estimation of ingested volume is increased (~22%) by perceived oral cold and carbonation, raising the idea that cold and perhaps CO2 induced-irritation sensations are included in how we normally encode water in the mouth and how we estimate the quantity of volume swallowed. These findings have implications for addressing inadequate hydration state in populations such as the elderly. PMID- 27685094 TI - Postdoctoral training in clinical neuropsychology in America: how did we get here and where do recent applicants suggest we go next? AB - OBJECTIVE: The United States appears to be the only country which typically requires completion of a two-year postdoctoral fellowship for one to be considered competent to practice clinical neuropsychology. We review the history of how this came to be in the United States. Further, we describe obstacles that postdoctoral trainees face during this stage of training. METHOD: We first describe the most significant events leading to the requirement of a two-year fellowship in clinical neuropsychology. Next, we describe factors that trainees face when selecting and completing postdoctoral training. Finally, we review the results of the most recent annual survey of applicants for postdoctoral training to measure their experiences. RESULTS: Postdoctoral training in the United States is a relatively recent requirement in neuropsychology. Trainees face many obstacles when obtaining a postdoctoral position some of which can be addressed by the field. CONCLUSIONS: Training in Clinical Neuropsychology in the United States has evolved considerably over at least the last 45 or so years to the point that a two-year postdoctoral fellowship is now required for one to be a candidate for board certification through the American Board of Clinical Neuropsychology. We review many of the challenges that postdoctoral trainees face and provide survey data to describe their experiences and preferences. PMID- 27685095 TI - [Sporadic Lymphangioleiomyomatosis (sLAM) and Tuberous Sclerosis Complex (TSC) - Pulmonary Manifestations]. PMID- 27685096 TI - Visualization of Vascular and Parenchymal Regeneration after 70% Partial Hepatectomy in Normal Mice. AB - A modified silicone injection procedure was used for visualization of the hepatic vascular tree. This procedure consisted of in-vivo injection of the silicone compound, via a 26 G catheter, into the portal or hepatic vein. After silicone injection, organs were explanted and prepared for ex-vivo micro-CT (uCT) scanning. The silicone injection procedure is technically challenging. Achieving a successful outcome requires extensive microsurgical experience from the surgeon. One of the challenges of this procedure involves determining the adequate perfusion rate for the silicone compound. The perfusion rate for the silicone compound needs to be defined based on the hemodynamic of the vascular system of interest. Inappropriate perfusion rate can lead to an incomplete perfusion, artificial dilation and rupturing of vascular trees. The 3D reconstruction of the vascular system was based on CT scans and was achieved using preclinical software such as HepaVision. The quality of the reconstructed vascular tree was directly related to the quality of silicone perfusion. Subsequently computed vascular parameters indicative of vascular growth, such as total vascular volume, were calculated based on the vascular reconstructions. Contrasting the vascular tree with silicone allowed for subsequent histological work-up of the specimen after uCT scanning. The specimen can be subjected to serial sectioning, histological analysis and whole slide scanning, and thereafter to 3D reconstruction of the vascular trees based on histological images. This is the prerequisite for the detection of molecular events and their distribution with respect to the vascular tree. This modified silicone injection procedure can also be used to visualize and reconstruct the vascular systems of other organs. This technique has the potential to be extensively applied to studies concerning vascular anatomy and growth in various animal and disease models. PMID- 27685097 TI - Resolving macromolecular structures from electron cryo-tomography data using subtomogram averaging in RELION. AB - Electron cryo-tomography (cryo-ET) is a technique that is used to produce 3D pictures (tomograms) of complex objects such as asymmetric viruses, cellular organelles or whole cells from a series of tilted electron cryo-microscopy (cryo EM) images. Averaging of macromolecular complexes found within tomograms is known as subtomogram averaging, and this technique allows structure determination of macromolecular complexes in situ. Subtomogram averaging is also gaining in popularity for the calculation of initial models for single-particle analysis. We describe herein a protocol for subtomogram averaging from cryo-ET data using the RELION software (http://www2.mrc-lmb.cam.ac.uk/relion). RELION was originally developed for cryo-EM single-particle analysis, and the subtomogram averaging approach presented in this protocol has been implemented in the existing workflow for single-particle analysis so that users may conveniently tap into existing capabilities of the RELION software. We describe how to calculate 3D models for the contrast transfer function (CTF) that describe the transfer of information in the imaging process, and we illustrate the results of classification and subtomogram averaging refinement for cryo-ET data of purified hepatitis B capsid particles and Saccharomyces cerevisiae 80S ribosomes. Using the steps described in this protocol, along with the troubleshooting and optimization guidelines, high-resolution maps can be obtained in which secondary structure elements are resolved subtomogram. PMID- 27685098 TI - A simple approach for measuring FRET in fluorescent biosensors using two-photon microscopy. AB - Genetically encoded fluorescent protein (FP)-based biosensor probes are useful tools for monitoring cellular events in living cells and tissues. Because these probes were developed for one-photon excitation approaches, their broad two photon excitation (2PE) and poorly understood photobleaching characteristics have made their implementation in studies using two-photon laser-scanning microscopy (TPLSM) challenging. Here we describe a protocol that simplifies the use of Forster resonance energy transfer (FRET)-based biosensors in TPLSM. First, the TPLSM system is evaluated and optimized using FRET standards expressed in living cells, which enables the determination of spectral bleed-through (SBT) and the confirmation of FRET measurements from the known standards. Next, we describe how to apply the approach experimentally using a modified version of the A kinase activity reporter (AKAR) protein kinase A (PKA) biosensor as an example-first in cells in culture and then in hepatocytes in the liver of living mice. The microscopic imaging can be accomplished in a day in laboratories that routinely use TPLSM. PMID- 27685099 TI - Separation and parallel sequencing of the genomes and transcriptomes of single cells using G&T-seq. AB - Parallel sequencing of a single cell's genome and transcriptome provides a powerful tool for dissecting genetic variation and its relationship with gene expression. Here we present a detailed protocol for G&T-seq, a method for separation and parallel sequencing of genomic DNA and full-length polyA(+) mRNA from single cells. We provide step-by-step instructions for the isolation and lysis of single cells; the physical separation of polyA(+) mRNA from genomic DNA using a modified oligo-dT bead capture and the respective whole-transcriptome and whole-genome amplifications; and library preparation and sequence analyses of these amplification products. The method allows the detection of thousands of transcripts in parallel with the genetic variants captured by the DNA-seq data from the same single cell. G&T-seq differs from other currently available methods for parallel DNA and RNA sequencing from single cells, as it involves physical separation of the DNA and RNA and does not require bespoke microfluidics platforms. The process can be implemented manually or through automation. When performed manually, paired genome and transcriptome sequencing libraries from eight single cells can be produced in ~3 d by researchers experienced in molecular laboratory work. For users with experience in the programming and operation of liquid-handling robots, paired DNA and RNA libraries from 96 single cells can be produced in the same time frame. Sequence analysis and integration of single-cell G&T-seq DNA and RNA data requires a high level of bioinformatics expertise and familiarity with a wide range of informatics tools. PMID- 27685100 TI - Mapping 3D genome architecture through in situ DNase Hi-C. AB - With the advent of massively parallel sequencing, considerable work has gone into adapting chromosome conformation capture (3C) techniques to study chromosomal architecture at a genome-wide scale. We recently demonstrated that the inactive murine X chromosome adopts a bipartite structure using a novel 3C protocol, termed in situ DNase Hi-C. Like traditional Hi-C protocols, in situ DNase Hi-C requires that chromatin be chemically cross-linked, digested, end-repaired, and proximity-ligated with a biotinylated bridge adaptor. The resulting ligation products are optionally sheared, affinity-purified via streptavidin bead immobilization, and subjected to traditional next-generation library preparation for Illumina paired-end sequencing. Importantly, in situ DNase Hi-C obviates the dependence on a restriction enzyme to digest chromatin, instead relying on the endonuclease DNase I. Libraries generated by in situ DNase Hi-C have a higher effective resolution than traditional Hi-C libraries, which makes them valuable in cases in which high sequencing depth is allowed for, or when hybrid capture technologies are expected to be used. The protocol described here, which involves ~4 d of bench work, is optimized for the study of mammalian cells, but it can be broadly applicable to any cell or tissue of interest, given experimental parameter optimization. PMID- 27685102 TI - Evaluation of cassette-based digital radiography detectors using standardized image quality metrics: AAPM TG-150 Draft Image Detector Tests. AB - The purpose of this study was to evaluate several of the standardized image quality metrics proposed by the American Association of Physics in Medicine (AAPM) Task Group 150. The task group suggested region-of-interest (ROI)-based techniques to measure nonuniformity, minimum signal-to-noise ratio (SNR), number of anomalous pixels, and modulation transfer function (MTF). This study evaluated the effects of ROI size and layout on the image metrics by using four different ROI sets, assessed result uncertainty by repeating measurements, and compared results with two commercially available quality control tools, namely the Carestream DIRECTVIEW Total Quality Tool (TQT) and the GE Healthcare Quality Assurance Process (QAP). Seven Carestream DRX-1C (CsI) detectors on mobile DR systems and four GE FlashPad detectors in radiographic rooms were tested. Images were analyzed using MATLAB software that had been previously validated and reported. Our values for signal and SNR nonuniformity and MTF agree with values published by other investigators. Our results show that ROI size affects nonuniformity and minimum SNR measurements, but not detection of anomalous pixels. Exposure geometry affects all tested image metrics except for the MTF. TG 150 metrics in general agree with the TQT, but agree with the QAP only for local and global signal nonuniformity. The difference in SNR nonuniformity and MTF values between the TG-150 and QAP may be explained by differences in the calculation of noise and acquisition beam quality, respectively. TG-150's SNR nonuniformity metrics are also more sensitive to detector nonuniformity compared to the QAP. Our results suggest that fixed ROI size should be used for consistency because nonuniformity metrics depend on ROI size. Ideally, detector tests should be performed at the exact calibration position. If not feasible, a baseline should be established from the mean of several repeated measurements. Our study indicates that the TG-150 tests can be used as an independent standardized procedure for detector performance assessment. PMID- 27685101 TI - Radiation leakage dose from Elekta electron collimation system. AB - This study provided baseline data required for a greater project, whose objective was to design a new Elekta electron collimation system having significantly lighter electron applicators with equally low out-of field leakage dose. Specifically, off-axis dose profiles for the electron collimation system of our uniquely configured Elekta Infinity accelerator with the MLCi2 treatment head were measured and calculated for two primary purposes: 1) to evaluate and document the out-of-field leakage dose in the patient plane and 2) to validate the dose distributions calculated using a BEAMnrc Monte Carlo (MC) model for out of-field dose profiles. Off-axis dose profiles were measured in a water phantom at 100 cm SSD for 1 and 2 cm depths along the in-plane, cross-plane, and both diagonal axes using a cylindrical ionization chamber with the 10 * 10 and 20 * 20 cm2 applicators and 7, 13, and 20 MeV beams. Dose distributions were calculated using a previously developed BEAMnrc MC model of the Elekta Infinity accelerator for the same beam energies and applicator sizes and compared with measurements. Measured results showed that the in-field beam flatness met our acceptance criteria (+/- 3% on major and +/-4% on diagonal axes) and that out-of-field mean and maximum percent leakage doses in the patient plane met acceptance criteria as specified by the International Electrotechnical Commission (IEC). Cross-plane out of-field dose profiles showed greater leakage dose than in-plane profiles, attributed to the curved edges of the upper X-ray jaws and multileaf collimator. Mean leakage doses increased with beam energy, being 0.93% and 0.85% of maximum central axis dose for the 10 * 10 and 20 * 20 cm2 applicators, respectively, at 20 MeV. MC calculations predicted the measured dose to within 0.1% in most profiles outside the radiation field; however, excluding model-ing of nontrimmer applicator components led to calculations exceeding measured data by as much as 0.2% for some regions along the in-plane axis. Using EGSnrc LATCH bit filtering to separately calculate out-of-field leakage dose components (photon dose, primary electron dose, and electron dose arising from interactions in various collimating components), MC calculations revealed that the primary electron dose in the out-of-field leakage region was small and decreased as beam energy increased. Also, both the photon dose component and electron dose com-ponent resulting from collimator scatter dominated the leakage dose, increasing with increasing beam energy. We concluded that our custom Elekta Infinity with the MLCi2 treatment head met IEC leakage dose criteria in the patient plane. Also, accuracy of our MC model should be sufficient for our use in the design of a new, improved electron collimation system. PMID- 27685103 TI - Surface imaging, laser positioning or volumetric imaging for breast cancer with nodal involvement treated by helical TomoTherapy. AB - A surface imaging system, Catalyst (C-Rad), was compared with laser-based positioning and daily mega voltage computed tomography (MVCT) setup for breast patients with nodal involvement treated by helical TomoTherapy. Catalyst-based positioning performed better than laser-based positioning. The respective modalities resulted in a standard deviation (SD), 68% confidence interval (CI) of positioning of left-right, craniocaudal, anterior-posterior, roll: 2.4 mm, 2.7 mm, 2.4 mm, 0.9 degrees for Catalyst positioning, and 6.1 mm, 3.8 mm, 4.9 mm, 1.1 degrees for laser-based positioning, respectively. MVCT-based precision is a combination of the interoperator variability for MVCT fusion and the patient movement during the time it takes for MVCT and fusion. The MVCT fusion interoperator variability for breast patients was evaluated at one SD left-right, craniocaudal, ant-post, roll as: 1.4 mm, 1.8 mm, 1.3 mm, 1.0 degrees . There was no statistically significant difference between the automatic MVCT registration result and the manual adjustment; the automatic fusion results were within the 95% CI of the mean result of 10 users, except for one specific case where the patient was positioned with large yaw. We found that users add variability to the roll correction as the automatic registration was more consistent. The patient position uncertainty confidence interval was evaluated as 1.9 mm, 2.2 mm, 1.6 mm, 0.9 degrees after 4 min, and 2.3 mm, 2.8 mm, 2.2 mm, 1 degrees after 10 min. The combination of this patient movement with MVCT fusion interoperator variability results in total standard deviations of patient posi-tion when treatment starts 4 or 10 min after initial positioning of, respectively: 2.3 mm, 2.8 mm, 2.0 mm, 1.3 degrees and 2.7 mm, 3.3 mm, 2.6 mm, 1.4 degrees . Surface based positioning arrives at the same precision when taking into account the time required for MVCT imaging and fusion. These results can be used on a patient-per patient basis to decide which positioning system performs the best after the first 5 fractions and when daily MVCT can be omitted. Ideally, real-time monitoring is required to reduce important intrafraction movement. PMID- 27685106 TI - Is the dose distribution distorted in IMRT and RapidArc treatment when patient plans are swapped across beam-matched machines? AB - The purpose of this study is to evaluate the degree of dose distribution distortion in advanced treatments like IMRT and RapidArc when patient plans are swapped across dosimetrically equivalent so-called "beam-matched" machines. For this purpose the entire work is divided into two stages. At forefront stage all basic beam properties of 6 MV X-rays like PDD, profiles, output factors, TPR20/10 and MLC transmission of two beam-matched machines - Varian Clinac iX and Varian 600 C/D Unique - are compared and evaluated for differences. At second stage 40 IMRT and RapidArc patient plans from the pool of head and neck (H&N) and pelvis sites are selected for the study. The plans are swapped across the machines for dose recalculation and the DVHs of target and critical organs are evaluated for dose differences. Following this, the accuracy of the beam-matching at the TPS level for treatments like IMRT and RapidArc are compared. On PDD, profile (central 80%) and output factor comparison between the two machines, a maxi-mum percentage disagreement value of -2.39%, -2.0% and -2.78%, respectively, has been observed. The maximum dose difference observed at volumes in IMRT and RapidArc treatments for H&N dose prescription of 69.3 Gy/33 fractions is 0.88 Gy and 0.82 Gy, respectively. Similarly, for pelvis, with a dose prescription of 50 Gy/25 fractions, a maximum dose difference of 0.55 Gy and 0.53 Gy is observed at volumes in IMRT and RapidArc treatments, respectively. Overall results of the swapped plans between two machines' 6 MV X-rays are well within the limits of accepted clinical tolerance. PMID- 27685104 TI - Secondary cancer-incidence risk estimates for external radiotherapy and high-dose rate brachytherapy in cervical cancer: phantom study. AB - This study was designed to estimate radiation-induced secondary cancer risks from high-dose-rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out-of-field organs were measured at various loca-tions inside an anthropomorphic phantom. Brachytherapy-associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out-of-field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy-induced secondary cancer incidence dur-ing cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy-associated secondary malignancies. PMID- 27685105 TI - Characteristics of quantitative perfusion parameters on dynamic contrast-enhanced MRI in mammographically occult breast cancer. AB - The purpose of this study was to compare the characteristics of quantitative per fusion parameters obtained from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in patients with mammographically occult (MO) breast cancers and those with mammographically visible (MV) breast cancers. Quantitative parameters (AUC, Ktrans, kep, ve, vp, and wi) from 13 MO breast cancers and 16 MV breast cancers were mapped after the DCE-MRI data were acquired. Various prog nostic factors, including axillary nodal status, estrogen receptor (ER), progesterone receptor (PR), Ki-67, p53, E-cadherin, and human epidermal growth factor receptor 2 (HER2) were obtained in each group. Fisher's exact test was used to compare any differences of the various prognostic factors between the two groups. The Mann- Whitney U test was applied to compare the quantitative parameters between these two groups. Finally, Spearman's correlation was used to investigate the relation-ships between perfusion indices and four factors - age, tumor size, Ki-67, and p53 - for each group. Although age, tumor size, and the prognostic factors were not statistically different between the two groups, the mean values of the quantitative parameters, except wi in the MV group, were higher than those in the MO group without statistical significance (p = 0.219). The kep value was significantly differ-ent between the two groups (p = 0.048), but the other parameters were not. In the MO group, vp with size, ve with p53, and Ktrans and vp with Ki-67 had significant correlations (p < 0.05). However, in the MV group, only kep showed significant correlation with age. The kep value was only the perfusion parameter of statistical significance between MO and MV breast cancers. PMID- 27685107 TI - Initial clinical experience with ArcCHECK for IMRT/VMAT QA. AB - Many devices designed for the purpose of performing patient-specific IMRT/VMAT QA are commercially available. In this work we report our experience and initial clinical results with the ArcCHECK. The ArcCHECK consists of a cylindrical array of diode detectors measuring entry and exit doses. The measured result is a cumulative dose displayed as a 2D matrix. The detector array requires both an absolute dose calibration, and a calibration of the detector response, relative to each other. In addition to the calibrations suggested by the manufacturer, various tests were performed in order to assess its stability and performance prior to clinical introduction. Tests of uniformity, linearity, and repetition rate dependence of the detector response were conducted and described in this work. Following initial test-ing, the ArcCHECK device was introduced in the clinic for routine patient-specific IMRT QA. The clinical results from one year of use were collected and analyzed. The gamma pass rates at the 3%/3 mm criterion were reported for 3,116 cases that included both IMRT and VMAT treatment plans delivered on 18 linear accelera-tors. The gamma pass rates were categorized based on the treatment site, treatment technique, type of MLCs, operator, ArcCHECK device, and LINAC model. We recorded the percent of failures at the clinically acceptable threshold of 90%. In addition, we calculated the threshold that encompasses two standard deviations (2 SD) (95%) of QAs (T95) for each category investigated. The commissioning measurements demonstrated that the device performed as expected. The uniformity of the detector response to a constant field arc delivery showed a 1% standard deviation from the mean. The variation in dose with changing repetition rate was within 1 cGy of the mean, while the measured dose showed a linear relation with delivered MUs. Our initial patient QA results showed that, at the clinically selected passing criterion, 4.5% of cases failed. On average T95 was 91%, rang-ing from 73% for gynecological sites to 96.5% for central nervous system sites. There are statistically significant differences in passing rates between IMRT and VMAT, high-definition (HD) and non HD MLCs, and different LINAC models (p-values << 0.001). An additional investigation into the failing QAs and a com-parison with ion-chamber measurements reveals that the differences observed in the passing rates between the different studied factors can be largely explained by the field size dependence of the device. Based on our initial experience with the ArcCHECK, our passing rates are, on average, consistent with values reported in the AAPM TG 119. However, the significant variations between QAs that were observed based on the size of the treatment fields may need to be corrected to improve the specificity and sensitivity of the device. PMID- 27685108 TI - Simultaneously integrated boost (SIB) spares OAR and reduces treatment time in locally advanced cervical cancer. AB - We performed a dosimetric comparison of sequential IMRT (sIMRT) and simul taneously integrated boost (SIB) IMRT to boost PET-avid lymph nodes while concurrently treating pelvic targets to determine the potential of SIB IMRT to reduce overall treatment duration in locally advanced cervical cancer. Ten patients receiving definitive radiation therapy were identified retrospectively. RTOG consensus guidelines were followed to delineate the clinical target volume and organs at risk (OAR), which were then expanded per IMRT consortium guidelines to yield the planning target volume (PTV). Dosimetric parameters for PTVs and OAR including conformity (CI95%) were collected and compared using Wilcoxon signed rank tests with Bonferroni correction. The median PTV volume was 1843 cc (1088 2225 cc) and the median boost volume was 43 cc (15-129 cc). Comparable target volume coverage was achieved with sIMRT and SIB plans, while hot spots were significantly reduced using SIB. SIB plans improved sparing for all OAR, though only rectum and small bowel doses were statistically significant. Comparing sIMRT and SIB plans averaged over all patients, rectal doses were V45: 70.8% vs. 64.5% (p = 0.002) and 0.1 cc: 50.7 Gy vs. 48.7 Gy (p = 0.006). For small bowel, sIMRT and SIB IMRT plans yielded V45: 13.4% vs. 11.4% (p = 0.006) and 1 cc: 54.4 Gy vs. 52.6 Gy (p = 0.006), respectively. Doses to femoral heads and blad-der trended towards significance in favor of SIB plans. The mean treatment time was 25 versus 29 days for SIB and sIMRT plans, respectively. When compared to sIMRT, SIB for treatment of nodal targets provides a significant, but small, dose reduction (3.8%-4.4%) to OAR, which leads to comparable biological dose despite higher fractional doses. Furthermore, SIB IMRT reduces overall treatment time and simplifies the planning process, and should be considered for targeting PET positive nodal disease in patients with locally advanced cervical cancer. PMID- 27685109 TI - Revisiting fetal dose during radiation therapy: evaluating treatment techniques and a custom shield. AB - To create a comprehensive dataset of peripheral dose (PD) measurements from a new generation of linear accelerators with and without the presence of a newly designed fetal shield, PD measurements were performed to evaluate the effects of depth, field size, distance from the field edge, collimator angle, and beam modi fiers for common treatment protocols and modalities. A custom fetal lead shield was designed and made for our department that allows external beam treatments from multiple angles while minimizing the need to adjust the shield during patient treatments. PD measurements were acquired for a comprehensive series of static fields on a stack of Solid Water. Additionally, PDs from various clinically relevant treatment scenarios for pregnant patients were measured using an anthropomorphic phantom that was abutted to a stack of Solid Water. As expected, the PD decreased as the distance from the field edge increased and the field size decreased. On aver-age, a PD reduction was observed when a 90 degrees collimator rotation was applied and/or when the tertiary MLCs and jaws defined the field aperture. However, the effect of the collimator rotation (90 degrees versus 0 degrees ) in PD reduction was not found to be clini-cally significant when the tertiary MLCs were used to define the field aperture. In the presence of both the MLCs and the fetal shield, the PD was reduced by 58% at a distance of 10 cm from the field edge. The newly designed fetal shield may effectively reduce fetal dose and is relatively easy to setup. Due to its design, we are able to use a broad range of treatment techniques and beam angles. We believe the acquired comprehensive PD dataset collected with and without the fetal shield will be useful for treatment teams to estimate fetal dose and help guide decisions on treat-ment techniques without the need to perform pretreatment phantom measurements. PMID- 27685110 TI - Translucent poly(vinyl alcohol) cryogel dosimeters for simultaneous dose buildup and monitoring during chest wall radiation therapy. AB - Chest wall radiation therapy treatment delivery was monitored using a 5 mm thick radiochromic poly(vinyl alcohol) cryogel that also provided buildup material. The cryogels were used to detect positioning errors and measure the impact of shifts for a chest wall treatment that was delivered to a RANDO phantom. The phantom was shifted by +/- 2, +/- 3, and +/- 5 mm from the planned position in the anterior/posterior (A/P) direction; these shifts represent setup errors and the uncertainty associated with lung filling during breath-hold. The two-dimensional absolute dose distributions measured in the cryogel at the planned position were compared with the distributions at all shifts from this position using gamma analysis (3%/3 mm, 10% threshold). For shifts of +/- 2, +/- 3, and +/- 5 mm the passing rates ranged from 94.3% to 95.6%, 74.0% to 78.8%, and 17.5% to 22.5%, respectively. These results are consistent with the same gamma analysis performed on dose planes calculated in the middle of the cryogel and on the phantom surface using our treatment plan-ning system, which ranged from 94.3% to 95.0%, 76.8% to 77.9%, and 23.5% to 24.3%, respectively. The Pinnacle dose planes were then scaled empirically and compared to the cryogel measurements. Using the same gamma metric, the pass rates ranged from 97.0% to 98.4%. The results of this study suggest that cryogels may be used as both a buildup material and to evaluate errors in chest wall treat-ment positioning during deep-inspiration breath-hold delivery. The cryogels are sensitive to A/P chest wall shifts of less than 3 mm, which potentially allows for the detection of clinically relevant errors. PMID- 27685111 TI - Verification measurements of an eMC algorithm using a 2D ion chamber array. AB - The aim of this study was to assess the suitability of the Im'RT MatriXX 2D ion chamber array for performing verification measurements on the Varian Eclipse electron Monte Carlo (eMC) algorithm for a range of clinical energies (6, 12, and 20 MeV) on a Varian 2100iX linear accelerator. Firstly, the suitability of the MatriXX for measuring percentage depth doses (PDD) in water was assessed, including characterization of the inherent buildup found in the MatriXX. Secondly the suitability of the MatriXX for measuring dose distributions in homogeneous and heterogeneous phantoms was assessed using gamma analysis at 3%/3 mm. It was found that after adjusting the PDD curves for the inherent buildup, that the position of R50,D measured using the MatriXX agreed to within 1 mm to the PDDs generated using the eMC algorithm for all energies used in this study. Gamma analysis at 3%/3mm showed very good agreement (> 95%) for all cases in both homogeneous and heterogeneous phantoms. It was concluded that the Im'RT MatriXX is a suitable device for performing eMC verification and could potentially be used for routine energy checks of electron beams. PMID- 27685112 TI - Implementation and evaluation of a protocol management system for automated review of CT protocols. AB - Protocol review is important to decrease the risk of patient injury and increase the consistency of CT image quality. A large volume of CT protocols makes manual review labor-intensive, error-prone, and costly. To address these challenges, we have developed a software system for automatically managing and monitoring CT proto-cols on a frequent basis. This article describes our experiences in the implementation and evaluation of this protocol monitoring system. In particular, we discuss various strategies for addressing each of the steps in our protocol monitoring workflow, which are: maintaining an accurate set of master protocols, retrieving protocols from the scanners, comparing scanner protocols to master protocols, reviewing flagged differences between the scanner and master protocols, and updating the scanner and/or master protocols. In our initial evaluation focusing only on abdo-men and pelvis protocols, we detected 309 modified protocols in a 24-week trial period. About one-quarter of these modified protocols were determined to contain inappropriate (i.e., erroneous) protocol parameter modifications that needed to be corrected on the scanner. The most frequently affected parameter was the series description, which was inappropriately modified 47 times. Two inappropriate modifications were made to the tube current, which is particularly important to flag as this parameter impacts both radiation dose and image quality. The CT protocol changes detected in this work provide strong motivation for the use of an automated CT protocol quality control system to ensure protocol accuracy and consistency. PMID- 27685113 TI - Dosimetric impact of cylinder size in high-dose rate vaginal cuff brachytherapy (VCBT) for primary endometrial cancer. AB - The purpose of this study was to evaluate the dosimetric impact of cylinder size in high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT). Sample plans of HDR VCBT in a list of cylinders ranging from 2.5 to 4 cm in diameter at 0.5 cm incre ment were created and analyzed. The doses were prescribed either at the 0.5cm depth with 5.5 Gy for 4 fractions or at the cylinder surface with 8.8 Gy for 4 frac-tions, in various treatment lengths. A 0.5 cm shell volume called PTV_Eval was contoured for each plan and served as the target volume for dosimetric evaluation. The cumulative and differential dose volume histograms (c-DVH and d DVH), mean doses (D-mean) and the doses covering 90% (D90), 10% (D10), and 5% (D5) of PTV_Eval were calculated. In the 0.5 cm depth regimen, the DVH curves were found to have shifted toward the lower dose zone when a larger cylinder was used, but in the surface regimen the DVH curves shifted toward the higher dose zone as the cylinder size increased. The D-means of the both regimens were between 6.9 and 7.8 Gy and dependent on the cylinder size but independent of the treatment length. A 0.5 cm variation of diameter could result in a 4% change of D mean. Average D90s were 5.7 (ranging from 5.6 to 5.8 Gy) and 6.1 Gy (from 5.7 to 6.4 Gy), respectively, for the 0.5 cm and surface regimens. Average D10 and D5 were 9.2 and 11 Gy, respectively, for the 0.5 cm depth regimen, and 8.9 and 9.7 Gy, respectively, for the surface regimen. D-mean, D90, D10, and D5 for other prescription doses could be calculated from the lookup tables of this study. Results indicated that the cylinder size has moderate dosimetric impact, and that both regimens are comparable in dosimetric quality. PMID- 27685114 TI - On the use of a convolution-superposition algorithm for plan checking in lung stereotactic body radiation therapy. AB - Stereotactic body radiation therapy (SBRT) aims to deliver a highly conformal ablative dose to a small target. Dosimetric verification of SBRT for lung tumors presents a challenge due to heterogeneities, moving targets, and small fields. Recent software (M3D) designed for dosimetric verification of lung SBRT treatment plans using an advanced convolution-superposition algorithm was evaluated. Ten lung SBRT patients covering a range of tumor volumes were selected. 3D CRT plans were created using the XiO treatment planning system (TPS) with the superposition algorithm. Dose was recalculated in the Eclipse TPS using the AAA algorithm, M3D verification software using the collapsed-cone-convolution algorithm, and in house Monte Carlo (MC). Target point doses were calculated with RadCalc software. Near-maximum, median, and near-minimum target doses, conformity indices, and lung doses were compared with MC as the reference calculation. M3D 3D gamma passing rates were compared with the XiO and Eclipse. Wilcoxon signed-rank test was used to compare each calculation method with XiO with a threshold of significance of p < 0.05. M3D and RadCalc point dose calculations were greater than MC by up to 7.7% and 13.1%, respectively, with M3D being statistically significant (s.s.). AAA and XiO calculated point doses were less than MC by 11.3% and 5.2%, respectively (AAA s.s.). Median and near-minimum and near-maximum target doses were less than MC when calculated with AAA and XiO (all s.s.). Near-maximum and median target doses were higher with M3D compared with MC (s.s.), but there was no difference in near-minimum M3D doses compared with MC. M3D-calculated ipsilateral lung V20 Gy and V5 Gy were greater than that calculated with MC (s.s.); AAA- and XiO-calculated V20 Gy was lower than that calculated with MC, but not statistically different to MC for V5 Gy. Nine of the 10 plans achieved M3D gamma passing rates greater than 95% and 80%for 5%/1 mm and 3%/1 mm criteria, respectively. M3D typically calculated a higher target and lung dose than MC for lung SBRT plans. The results show a range of calculated doses with different algorithms and suggest that M3D is in closer agree-ment with Monte Carlo, thus discrepancies between the TPS and M3D software will be observed for lung SBRT plans. M3D provides a useful supplement to verification of lung SBRT plans by direct measurement, which typically excludes patient specific heterogeneities. PMID- 27685115 TI - Diode-based transmission detector for IMRT delivery monitoring: a validation study. AB - The purpose of this work was to evaluate the potential of a new transmission detector for real-time quality assurance of dynamic-MLC-based radiotherapy. The accuracy of detecting dose variation and static/dynamic MLC position deviations was measured, as well as the impact of the device on the radiation field (surface dose, transmission). Measured dose variations agreed with the known variations within 0.3%. The measurement of static and dynamic MLC position deviations matched the known deviations with high accuracy (0.7-1.2 mm). The absorption of the device was minimal (~ 1%). The increased surface dose was small (1%-9%) but, when added to existing collimator scatter effects could become significant at large field sizes (>= 30 * 30 cm2). Overall the accuracy and speed of the device show good potential for real-time quality assurance. PMID- 27685116 TI - Technical Note: A respiratory monitoring and processing system based on computer vision: prototype and proof of principle. AB - Monitoring and controlling respiratory motion is a challenge for the accuracy and safety of therapeutic irradiation of thoracic tumors. Various commercial systems based on the monitoring of internal or external surrogates have been developed but remain costly. In this article we describe and validate Madibreast, an in house-made respiratory monitoring and processing device based on optical tracking of external markers. We designed an optical apparatus to ensure real-time submillimetric image resolution at 4 m. Using OpenCv libraries, we optically tracked high-contrast markers set on patients' breasts. Validation of spatial and time accuracy was performed on a mechanical phantom and on human breast. Madibreast was able to track motion of markers up to a 5 cm/s speed, at a frame rate of 30 fps, with submillimetric accuracy on mechanical phantom and human breasts. Latency was below 100 ms. Concomitant monitoring of three different locations on the breast showed discrepancies in axial motion up to 4 mm for deep breathing patterns. This low-cost, computer-vision system for real-time motion monitoring of the irradiation of breast cancer patients showed submillimetric accuracy and acceptable latency. It allowed the authors to highlight differences in surface motion that may be correlated to tumor motion.v. PMID- 27685117 TI - Investigation on using high-energy proton beam for total body irradiation (TBI). AB - This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow +/- 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were +/- 8.9%, +/- 9.0%, +/- 9.6%, and +/- 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. PMID- 27685118 TI - A noise power spectrum study of a new model-based iterative reconstruction system: Veo 3.0. AB - The purpose of this study was to evaluate performance of the third generation of model-based iterative reconstruction (MBIR) system, Veo 3.0, based on noise power spectrum (NPS) analysis with various clinical presets over a wide range of clinically applicable dose levels. A CatPhan 600 surrounded by an oval, fat equivalent ring to mimic patient size/shape was scanned 10 times at each of six dose levels on a GE HD 750 scanner. NPS analysis was performed on images reconstructed with various Veo 3.0 preset combinations for comparisons of those images reconstructed using Veo 2.0, filtered back projection (FBP) and adaptive statistical iterative reconstruc-tion (ASiR). The new Target Thickness setting resulted in higher noise in thicker axial images. The new Texture Enhancement function achieved a more isotropic noise behavior with less image artifacts. Veo 3.0 provides additional reconstruction options designed to allow the user choice of balance between spatial resolution and image noise, relative to Veo 2.0. Veo 3.0 provides more user selectable options and in general improved isotropic noise behavior in comparison to Veo 2.0. The overall noise reduction performance of both versions of MBIR was improved in comparison to FBP and ASiR, especially at low-dose levels. PMID- 27685119 TI - MRI quantification of pancreas motion as a function of patient setup for particle therapy -a preliminary study. AB - Particle therapy (PT) has shown positive therapeutic results in local control of locally advanced pancreatic lesions. PT effectiveness is highly influenced by target localization accuracy both in space, since the pancreas is located in proximity to radiosensitive vital organs, and in time as it is subject to substantial breathing-related motion. The purpose of this preliminary study was to quantify pancreas range of motion under typical PT treatment conditions. Three common immobilization devices (vacuum cushion, thermoplastic mask, and compressor belt) were evaluated on five male patients in prone and supine positions. Retrospective four-dimensional magnetic resonance imaging data were reconstructed for each condition and the pancreas was manually segmented on each of six breathing phases. A k-means algorithm was then applied on the manually segmented map in order to obtain clusters representative of the three pancreas segments: head, body, and tail. Centers of mass (COM) for the pancreas and its segments were computed, as well as their displacements with respect to a reference breathing phase (beginning exhalation). The median three-dimensional COM displacements were in the range of 3 mm. Latero-lateral and superior-inferior directions had a higher range of motion than the anterior-posterior direction. Motion analysis of the pancreas segments showed slightly lower COM displacements for the head cluster compared to the tail cluster, especially in prone position. Statistically significant differences were found within patients among the investigated setups. Hence a patient-specific approach, rather than a general strategy, is suggested to define the optimal treatment setup in the frame of a millimeter positioning accuracy. PMID- 27685120 TI - Patient-specific 17-segment myocardial modeling on a bull's eye map. AB - The purpose of this study was to develop and validate cardiac computed tomog raphy (CT) quantitative analysis software with a patient-specific, 17-segment myocardial model that uses electrocardiogram (ECG)-gated cardiac CT images to differentiate between normal controls and severe aortic stenosis (AS) patients. ECG-gated cardiac CT images from 35 normal controls and 144 AS patients were semiautomatically segmented to create a patient-specific, 17-segment myocardial model. Two experts then manually determined the anterior and posterior interven tricular grooves to be boundaries between the 1st and 2nd segments and between the 3rd and 4th segments, respectively, to correct the model. Each segment was automatically identified as follows. The outer angle of two boundaries was divided to differentiate the 1st, 4th, 5th, and 6th segments in the basal plane, whereas the inner angle divided the 2nd and 3rd segments. The segments of the midplane were similarly divided. Segmental area distributions were quantitatively evaluated on the bull's-eye map on the basis of the morphological boundaries by measuring the area of each segment. Segmental areas of severe AS patients and normal controls were significantly different (t-test, all p-values < 0.011) in the proposed model because the septal regions of the severe AS patients were smaller than those of normal controls and the difference was enough to divide the two groups. The capabilities of the 2D segmental areas (p < 0.011) may be equivalent to those of 3D segmental analysis (all p-values < 0.001) for differentiating the two groups (t-test, all p-values < 0.001). The proposed method is superior to the conventional 17-segment in relation to reflection of patient-specific morphological variation and allows to obtain a more precise mapping between segments and the AHA recommended nomenclature. It can be used to differentiate severer AS patients and normal controls and also helps to understand the left ventricular morphology at a glance. PMID- 27685122 TI - A comparative study of identical VMAT plans with and without jaw tracking technique. AB - The unwanted radiation transmission through the multileaf collimators could be reduced by the jaw tracking technique which is commercially available on Varian TrueBeam accelerators. On the basis of identical plans, this study aims to investigate the dosimetric impact of jaw tracking on the volumetric-modulated arc therapy (VMAT) plans. Using Eclipse treatment planning system (TPS), 40 jaw tracking VMAT plans with various tumor volumes and shapes were optimized. Fixed jaw plans were created by editing the jaw coordinates of the jaw-tracking plans while other parameters were identical. The deliverability of this artificial modification was verified using COMPASS system via three-dimentional gamma analysis between the measurement-based reconstruction and the TPS-calculated dose distribution. Dosimetric parameters of dose-volume histogram (DVH) were compared to assess the improvement of dose sparing for organs at risk (OARs) in jaw tracking plans. COMPASS measurements demonstrated that over 96.9% of structure volumes achieved gamma values less than 1.00 at criteria of 3 mm/3%. The reduction magnitudes of maximum and mean dose to various OARs ranged between 0.06% ~ 6.76% (0.04 ~ 7.29 Gy) and 0.09% ~ 7.81% (0.02 ~ 2.78 Gy), respectively, using jaw tracking, agreeing with the disparities of radiological characteristics between MLC and jaws. Jaw tracking does not change the delivery efficiency and total monitor units. The dosimetric comparison of VMAT plans with and without jaw tracking confirms the physics hypotheses that reduced transmission through tracking jaws will reduce doses to OARs without sacrificing the target dose coverage because it is meant to be covered by radiation beams going through the opening. PMID- 27685123 TI - Clinical experience with planning, quality assurance, and delivery of burst-mode modulated arc therapy. AB - "Burst-mode" modulated arc therapy (hereafter referred to as "mARC") is a form of volumetric-modulated arc therapy characterized by variable gantry rotation speed, static MLCs while the radiation beam is on, and MLC repositioning while the beam is off. We present our clinical experience with the planning techniques and plan quality assurance measurements of mARC delivery. Clinical mARC plans for five representative cases (prostate, low-dose-rate brain, brain with partial-arc vertex fields, pancreas, and liver SBRT) were generated using a Monte Carlo-based treatment planning system. A conventional-dose-rate flat 6 MV and a high-dose rate non-flat 7 MV beam are available for planning and delivery. mARC plans for intact-prostate cases can typically be created using one 360 degrees arc, and treatment times per fraction seldom exceed 6 min using the flat beam; using the nonflat beam results in slightly higher MU per fraction, but also in delivery times less than 4 min and with reduced mean dose to distal organs at risk. mARC also has utility in low-dose-rate brain irradiation; mARC fields can be designed which deliver a uniform 20 cGy dose to the PTV in approximately 3-minute intervals, making it a viable alternative to conventional 3D CRT. For brain cases using noncoplanar arcs, delivery time is approximately six min using the nonflat beam. For pancreas cases using the nonflat beam, two overlapping 360 degrees arcs are required, and delivery times are approximately 10 min. For liver SBRT, the time to deliver 800 cGy per frac-tion is at least 12 min. Plan QA measurements indicate that the mARC delivery is consistent with the plan calculation for all cases. mARC has been incorporated into routine practice within our clinic; currently, on average approximately 15 patients per day are treated using mARC; and with the exception of LDR brain cases, all are treated using the nonflat beam. PMID- 27685124 TI - Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases. AB - We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. PMID- 27685125 TI - Evaluation of the uncertainty in an EBT3 film dosimetry system utilizing net optical density. AB - Radiochromic film has become an important tool to verify dose distributions for intensity-modulated radiotherapy (IMRT) and quality assurance (QA) procedures. A new radiochromic film model, EBT3, has recently become available, whose composition and thickness of the sensitive layer are the same as those of previous EBT2 films. However, a matte polyester layer was added to EBT3 to prevent the formation of Newton's rings. Furthermore, the symmetrical design of EBT3 allows the user to eliminate side-orientation dependence. This film and the flatbed scanner, Epson Perfection V750, form a dosimetry system whose intrinsic characteristics were studied in this work. In addition, uncertainties associated with these intrinsic characteristics and the total uncertainty of the dosimetry system were determined. The analysis of the response of the radiochromic film (net optical density) and the fitting of the experimental data to a potential function yielded an uncertainty of 2.6%, 4.3%, and 4.1% for the red, green, and blue channels, respectively. In this work, the dosimetry system presents an uncertainty in resolving the dose of 1.8% for doses greater than 0.8 Gy and less than 6 Gy for red channel. The films irradiated between 0 and 120 Gy show differences in the response when scanned in portrait or landscape mode; less uncertainty was found when using the portrait mode. The response of the film depended on the position on the bed of the scanner, contributing an uncertainty of 2% for the red, 3% for the green, and 4.5% for the blue when placing the film around the center of the bed of scanner. Furthermore, the uniformity and reproducibility radiochromic film and reproducibility of the response of the scanner contribute less than 1% to the overall uncertainty in dose. Finally, the total dose uncertainty was 3.2%, 4.9%, and 5.2% for red, green, and blue channels, respectively. The above uncertainty values were obtained by mini-mizing the contribution to the total dose uncertainty of the film orientation and film homogeneity. PMID- 27685126 TI - A dosimetric comparison of copper and Cerrobend electron inserts. AB - The purpose of this work was to evaluate differences in dose resulting from the use of copper aperture inserts compared to lead-alloy (Cerrobend) aperture inserts for electron beam therapy. Specifically, this study examines if copper aperture inserts can be used clinically with the same commissioning data measured using lead-alloy aperture inserts. The copper inserts were acquired from .decimal, LLC and matching lead-alloy, Cerrobend inserts were constructed in house for 32 com-binations of nine square insert field sizes (2 * 2 to 20 * 20 cm2) and five applicator sizes (6 * 6 to 25 * 25 cm2). Percent depth-dose and off axis relative dose profiles were measured using an electron diode in water for select copper and Cerrobend inserts for a subset of applicators (6 * 6, 10 * 10, 25 * 25 cm2) and energies (6, 12, 20 MeV) at 100 and 110 cm source-to-surface distances (SSD) on a Varian Clinac 21EX accelerator. Dose outputs were measured for all field size-insert combina-tions and five available energies (6-20 MeV) at 100 cm SSD and for a smaller subset at 110 cm SSD. Using these data, 2D planar absolute dose distributions were generated and compared. Criteria for agreement were +/- 2% of maximum dose or 1 mm distance-to-agreement for 99% of points. A gamma analysis of the beam dosimetry showed 94 of 96 combinations of insert size, applicator, energy, and SSD were within the 2%/1 mm criteria for > 99% of points. Outside the field, copper inserts showed less bremsstrahlung dose under the insert compared to Cerrobend (greatest difference was 2.5% at 20 MeV and 100 cm SSD). This effect was most prominent at the highest energies for combinations of large applicators with small field sizes, causing some gamma analysis failures. Inside the field, more electrons scattered from the collimator edge of copper compared to Cerrobend, resulting in an increased dose at the field edge for copper at shallow depths (greatest increase was 1% at 20 MeV and 100 cm SSD). Dose differences decreased as the SSD increased, with no gamma failures at 110 cm SSD. Inserts for field sizes >= 6 * 6 cm2 at any energy, or for small fields (<= 4 * 4 cm2) at energies < 20 MeV, showed dosimetric differences less than 2%/1 mm for more than 99% of points. All areas of comparison criteria failures were from lower out-of-field dose under copper inserts due to a reduction in bremsstrahlung production, which is clinically beneficial in reducing dose to healthy tissue outside of the planned treatment volume. All field size-applicator size-energy combinations passed 3%/1 mm criteria for 100% of points. Therefore, it should be clinically acceptable to utilize copper insets with dose distributions measured with Cerrobend inserts for treatment planning dose calculations and monitor unit calculations. PMID- 27685127 TI - Surface dose variations in 6 and 10 MV flattened and flattening filter-free (FFF) photon beams. AB - As the use of linear accelerators operating in flattening filter-free (FFF) modes becomes more widespread, it is important to have an understanding of the surface doses delivered to patients with these beams. Flattening filter removal alters the beam quality and relative contributions of low-energy X-rays and contamination electrons in the beam. Having dosimetric data to describe the surface dose and buildup regions under a range of conditions for FFF beams is important if clinical decisions are to be made. An Elekta Synergy linac with standard MLCi head has been commissioned to run at 6 MV and 10 MV running with the flattening filter in or out. In this linac the 6 MV FFF beam has been energy matched to the clinical beam on the central axis (D10). The 10 MV beam energy has not been adjusted. The flattening filter in both cases is replaced by a thin (2 mm) stainless steel plate. A thin window parallel plate chamber has been used to measure a comprehensive set of surface dose data in these beams for variations in field size and SSD, and for the presence of attenuators (wedge, shadow tray, and treatment couch). Surface doses are generally higher in FFF beams for small field sizes and lower for large field sizes with a crossover at 10 * 10 cm2 at 6 MV and 25 * 25 cm2 at 10 MV. This trend is also seen in the presence of the wedge, shadow tray, and treatment couch. Only small differences (< 0.5%) are seen between the beams on varying SSD. At both 6 and 10 MV the filter-free beams show far less variation with field size than conventional beams. By removing the flattening filter, a source of contamination electrons is exchanged for a source of low-energy photons (as these are no longer attenuated). In practice these two components almost balance out. No significant effects on surface dose are expected by the introduction of FFF delivery. PMID- 27685128 TI - RadShield: semiautomated shielding design using a floor plan driven graphical user interface. AB - The purpose of this study was to introduce and describe the development of RadShield, a Java-based graphical user interface (GUI), which provides a base design that uniquely performs thorough, spatially distributed calculations at many points and reports the maximum air-kerma rate and barrier thickness for each barrier pursuant to NCRP Report 147 methodology. Semiautomated shielding design calculations are validated by two approaches: a geometry-based approach and a manual approach. A series of geometry-based equations were derived giv-ing the maximum air-kerma rate magnitude and location through a first derivative root finding approach. The second approach consisted of comparing RadShield results with those found by manual shielding design by an American Board of Radiology (ABR)-certified medical physicist for two clinical room situations: two adjacent catheterization labs, and a radiographic and fluoroscopic (R&F) exam room. RadShield's efficacy in finding the maximum air-kerma rate was compared against the geometry-based approach and the overall shielding recommendations by RadShield were compared against the medical physicist's shielding results. Percentage errors between the geometry-based approach and RadShield's approach in finding the magnitude and location of the maximum air-kerma rate was within 0.00124% and 14 mm. RadShield's barrier thickness calculations were found to be within 0.156 mm lead (Pb) and 0.150 mm lead (Pb) for the adjacent catheteriza tion labs and R&F room examples, respectively. However, within the R&F room example, differences in locating the most sensitive calculation point on the floor plan for one of the barriers was not considered in the medical physicist's calculation and was revealed by the RadShield calculations. RadShield is shown to accurately find the maximum values of air-kerma rate and barrier thickness using NCRP Report 147 methodology. Visual inspection alone of the 2D X-ray exam distribution by a medical physicist may not be sufficient to accurately select the point of maximum air-kerma rate or barrier thickness. PMID- 27685129 TI - Comprehensive dosimetric planning comparison for early-stage, non-small cell lung cancer with SABR: fixed-beam IMRT versus VMAT versus TomoTherapy. AB - Volumetric-modulated arc therapy (VMAT) is emerging as a leading technology in treating early-stage, non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR). However, two other modalities capable of deliver ing intensity-modulated radiation therapy (IMRT) include fixed-beam and helical TomoTherapy (HT). This study aims to provide an extensive dosimetric compari-son among these various IMRT techniques for treating early-stage NSCLC with SABR. Ten early-stage NSCLC patients were retrospectively optimized using three fixed-beam techniques via nine to eleven beams (high and low modulation step-and-shoot (SS), and sliding window (SW)), two VMAT techniques via two partial arcs (SmartArc (SA) and RapidArc (RA)), and three HT techniques via three different fan beam widths (1 cm, 2.5 cm, and 5 cm) for 80 plans total. Fixed-beam and VMAT plans were generated using flattening filter-free beams. SS and SA, HT treatment plans, and SW and RA were optimized using Pinnacle v9.1, Tomoplan v.3.1.1, and Eclipse (Acuros XB v11.3 algorithm), respectively. Dose-volume histogram statistics, dose conformality, and treatment delivery efficiency were analyzed. VMAT treatment plans achieved significantly lower values for contralat-eral lung V5Gy (p <= 0.05) compared to the HT plans, and significantly lower mean lung dose (p < 0.006) compared to HT 5 cm treatment plans. In the comparison between the VMAT techniques, a significant reduction in the total monitor units (p = 0.05) was found in the SA plans, while a significant decrease was observed in the dose falloff parameter, D2cm, (p = 0.05), for the RA treatments. The maximum cord dose was significantly reduced (p = 0.017) in grouped RA&SA plans com-pared to SS. Estimated treatment time was significantly higher for HT and fixed-beam plans compared to RA&SA (p < 0.001). Although, a significant difference was not observed in the RA vs. SA (p = 0.393). RA&SA outperformed HT in all parameters measured. Despite an increase in dose to the heart and bronchus, this study demonstrates that VMAT is dosimetrically advantageous in treating early-stage NSCLC with SABR compared to fixed-beam, while providing significantly shorter treatment times. PMID- 27685130 TI - Method and phantom to study combined effects of in-plane (x,y) and z-axis resolution for 3D CT imaging. AB - Increasingly, the advent of multislice CT scanners, volume CT scanners, and total body spiral acquisition modes has led to the use of Multi Planar Reconstruction and 3D datasets. In considering 3D resolution properties of a CT system it is important to note that both the in-plane (x,y) and z-axis (slice thickness) influence the visual-ization and detection of objects within the scanned volume. This study investigates ways to consider both the in-plane resolution and the z axis resolution in a single phantom wherein analytic or visualized analysis can yield information on these combined effects. A new phantom called the "Wave Phantom" is developed that can be used to sample the 3D resolution properties of a CT image, including in-plane (x,y) and z-axis information. The key development in this Wave Phantom is the incorporation of a z-axis aspect of a more traditional step (bar) resolution gauge phantom. The phantom can be examined visually wherein a cutoff level may be seen; and/or the analytic analysis of the various characteristics of the waveform profile by including amplitude, frequency, and slope (rate of climb) of the peaks, can be extracted from the Wave Pattern using mathematical analysis such as the Fourier transform. The combined effect of changes in in-plane resolution and z-axis (thickness), are shown, as well as the effect of changes in either in-plane resolu-tion, or z-axis thickness. Examples of visual images of the Wave pattern as well as the analytic characteristics of the various harmonics of a periodic Wave pattern resulting from changes in resolution filter and/or slice thickness, and position in the field of view are shown. The Wave Phantom offers a promising way to investigate 3D resolution results from combined effect of in-plane (x-y) and z-axis resolution as contrasted to the use of simple 2D resolution gauges that need to be used with separate measures of z-axis dependency, such as angled ramps. It offers both a visual pattern as well as a pattern amenable to analytic analysis using Fourier Transform methods, and is believed to offer an image quality test closer to the diagnostic task where the 2D image has the hidden third (z) axis effects. PMID- 27685131 TI - Technical Note: Out-of-field dose measurement at near surface with plastic scintillator detector. AB - Out-of-field dose depends on multiple factors, making peripheral dosimetry com plex. Only a few dosimeters have the required features for measuring peripheral dose. Plastic scintillator dosimeters (PSDs) offer numerous dosimetric advantages as required for out-of-field dosimetry. The purpose of this study is to determine the potential of using PSD as a surface peripheral dosimeter. Measurements were performed with a parallel-plate ion chamber, a small volume ion chamber, and with a PSD. Lateral-dose measurements (LDM) at 0.5 cm depth and depth-dose curve (PDD) were made and compared to the dose calculation provided by a treatment planning system (TPS). This study shows that a PSD can measure a dose as low as 0.51 +/- 0.17 cGy for photon beam and 0.58 +/- 0.20 cGy for electron beam with a difference of 0.2 and 0.1 cGy compared to a parallel-plate ion chamber. This study demonstrates the potential of using PSD as an out-of-field dosimeter since measure-ments with PSD avoid averaging over a too-large depth, at 1 mm diameter, and can make precise measurement at very low dose. Also, electronic equilibrium is easier to reach with PSD due to its small sensitive volume and its water equivalence. PMID- 27685132 TI - An EPID-based system for gantry-resolved MLC quality assurance for VMAT. AB - Multileaf collimator (MLC) positions should be precisely and independently mea sured as a function of gantry angle as part of a comprehensive quality assurance (QA) program for volumetric-modulated arc therapy (VMAT). It is also ideal that such a QA program has the ability to relate MLC positional accuracy to patient specific dosimetry in order to determine the clinical significance of any detected MLC errors. In this work we propose a method to verify individual MLC trajectories during VMAT deliveries for use as a routine linear accelerator QA tool. We also extend this method to reconstruct the 3D patient dose in the treatment planning sys-tem based on the measured MLC trajectories and the original DICOM plan file. The method relies on extracting MLC positions from EPID images acquired at 8.41fps during clinical VMAT deliveries. A gantry angle is automatically tagged to each image in order to obtain the MLC trajectories as a function of gantry angle. This analysis was performed for six clinical VMAT plans acquired at monthly intervals for three months. The measured trajectories for each delivery were compared to the MLC positions from the DICOM plan file. The maximum mean error detected was 0.07 mm and a maximum root-mean-square error was 0.8 mm for any leaf of any delivery. The sensitivity of this system was characterized by introducing random and systematic MLC errors into the test plans. It was demonstrated that the system is capable of detecting random and systematic errors on the range of 1-2mm and single leaf calibration errors of 0.5 mm. The methodology developed in the work has potential to be used for efficient routine linear accelerator MLC QA and pretreatment patient-specific QA and has the ability to relate measured MLC positional errors to 3D dosimetric errors within a patient volume. PMID- 27685133 TI - Correlation of quantitative dynamic contrast-enhanced MRI with microvascular density in necrotic, partial necrotic, and viable liver tumors in a rabbit model. AB - The purpose of this study was to examine the correlation of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with microvessel density (MVD) in necrotic, partial necrotic, and viable tumors using a rabbit VX2 liver tumor model. Nine rabbits were used for this study. The complete necrotic area (CNA), partial necrotic area (PNA), and viable tumor area (VTA) of liver tumors were experimentally induced by radiofrequency ablation (RFA). DCE-MRI data were processed based on the extended Kety model to estimate Ktrans, ve and vp parameters. The boundaries among CNA, PNA, and VTA were delineated based on H&E stain images, and MVD was assessed for each subregion of each VX2 tumor based. There were no correlations between ph-parameters (Ktrans, ve, and vp) and MVD for CNA. For PNA, the Ktrans values were positively correlated with the MVD (r = 0.8124, p < 0.001). For VTA, we found a positive correlation between Ktrans values and the MVD (r = 0.5743, p < 0.05). Measuring from both the PNA and the VTA, mean Ktrans values were positively correlated with mean MVD (r = 0.8470, p < 0.0001). In a rabbit VX2 liver tumor model, Ktrans values correlated well with MVD counts of PNA and VTA in liver tumors. PMID- 27685134 TI - Dosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcsDosimetric validation for an automatic brain metastases planning software using single-isocenter dynamic conformal arcs. AB - An automatic brain-metastases planning (ABMP) software has been installed in our institution. It is dedicated for treating multiple brain metastases with radiosurgery on linear accelerators (linacs) using a single-setup isocenter with noncoplanar dynamic conformal arcs. This study is to validate the calculated absolute dose and dose distribution of ABMP. Three types of measurements were performed to validate the planning software: 1, dual micro ion chambers were used with an acrylic phantom to measure the absolute dose; 2, a 3D cylindrical phantom with dual diode array was used to evaluate 2D dose distribution and point dose for smaller targets; and 3, a 3D pseudo-in vivo patient-specific phantom filled with polymer gels was used to evaluate the accuracy of 3D dose distribution and radia-tion delivery. Micro chamber measurement of two targets (volumes of 1.2 cc and 0.9 cc, respectively) showed that the percentage differences of the absolute dose at both targets were less than 1%. Averaged GI passing rate of five different plans measured with the diode array phantom was above 98%, using criteria of 3% dose difference, 1 mm distance to agreement (DTA), and 10% low dose threshold. 3D gel phantom measurement results demonstrated a 3D displacement of nine targets of 0.7 +/- 0.4 mm (range 0.2 ~ 1.1 mm). The averaged two dimensional (2D) GI passing rate for several region of interests (ROI) on axial slices that encompass each one of the nine targets was above 98% (5% dose difference, 2 mm DTA, and 10% low-dose threshold). Measured D95, the minimum dose that covers 95% of the target volume, of the nine targets was 0.7% less than the calculated D95. Three different types of dosimetric verification methods were used and proved the dose calculation of the new automatic brain metastases planning (ABMP) software was clinical acceptable. The 3D pseudo-in vivo patient specific gel phantom test also served as an end-to-end test for validating not only the dose calculation, but the treatment delivery accuracy as well. PMID- 27685135 TI - Characterization of a 2.5 MV inline portal imaging beam. AB - A new megavoltage (MV) energy was recently introduced on Varian TrueBeam linear accelerators for imaging applications. This work describes the experimental characterization of a 2.5 MV inline portal imaging beam for commissioning, routine clinical use, and quality assurance purposes. The beam quality of the 2.5 MV beam was determined by measuring a percent depth dose, PDD, in water phantom for 10 * 10 cm2 field at source-to-surface distance 100 cm with a CC13 ion chamber, plane parallel Markus chamber, and GafChromic EBT3 film. Absolute dosimetric output calibration of the beam was performed using a traceable calibrated ionization chamber, following the AAPM Task Group 51 procedure. EBT3 film measurements were also performed to measure entrance dose. The output stability of the imaging beam was monitored for five months. Coincidence of 2.5 MV imaging beam with 6 MV therapy beam was verified with hidden-target cubic phantom. Image quality was studied using the Leeds and QC3 phantom. The depth of maximum dose, dmax, and percent dose at 10 cm depth were, respectively, 5.7 mm and 51.7% for CC13, 6.1 mm and 51.9% for Markus chamber, and 5.1 mm and 51.9% for EBT3 film. The 2.5 MV beam quality is slightly inferior to that of a 60Co teletherapy beam; however, an estimated kQ of 1.00 was used for output calibration purposes. The beam output was found to be stable to within 1% over a five-month period. The relative entrance dose as measured with EBT3 films was 63%, compared to 23% for a clinical 6 MV beam for a 10 * 10 cm2 field. Overall coincidence of the 2.5 MV imaging beam with the 6 MV clinical therapy beam was within 0.2 mm. Image quality results for two com-monly used imaging phantoms were superior for the 2.5 MV beam when compared to the conventional 6 MV beam. The results from measurements on two TrueBeam accelerators show that 2.5 MV imaging beam is slightly softer than a therapeutic 60Co beam, it provides superior image quality than a 6 MV therapy beam, and has excellent output stability. These 2.5 MV beam characterization results can serve as reference for clinics planning to commission and use this novel energy-image modality. PMID- 27685136 TI - Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy. AB - This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 MUSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure. PMID- 27685137 TI - Comparison of automatic image registration uncertainty for three IGRT systems using a male pelvis phantom. AB - A series of phantom images using the CIRS Virtual Human Male Pelvis was acquired across available dose ranges for three image-guided radiotherapy (IGRT) imaging systems: Elekta XVI CBCT, Varian TrueBeam CBCT, and TomoTherapy MV CT. Each image was registered to a fan-beam CT within the XVI software 100 times with random initial offsets. The residual registration error was analyzed to assess the role of imaging hardware and reconstruction in the uncertainty of the IGRT process. Residual translation errors were similar for all systems and < 0.5 mm. Over the clinical dose range for prostate IGRT images (10-25 mGy), all imaging systems provided acceptable matches in > 90% of registrations when incorporating residual rotational error using a dual quaternion derived distance metric. Outside normal dose settings, large uncertainties were observed at very low and very high dose levels. No trend between initial offset and residual registration error was observed. Patient images may incur higher uncertainties than this phantom study; however, these results encourage automatic matching for standard dose settings with review by treatment staff. PMID- 27685138 TI - Difference in dose-volumetric data between the analytical anisotropic algorithm, the dose-to-medium, and the dose-to-water reporting modes of the Acuros XB for lung stereotactic body radiation therapy. AB - The purpose of this study was to evaluate the difference in dose-volumetric data between the analytical anisotropic algorithms (AAA) and the two dose reporting modes of the Acuros XB, namely, the dose to water (AXB_Dw) and dose to medium (AXB_Dm) in lung stereotactic body radiotherapy (SBRT). Thirty-eight plans were generated using the AXB_Dm in Eclipse Treatment Planning System (TPS) and then recalculated with the AXB_Dw and AAA, using identical beam setup. A dose of 50 Gy in 4 fractions was prescribed to the isocenter and the planning target volume (PTV) D95%. The isocenter was always inside the PTV. The following dose volumetric parameters were evaluated; D2%, D50%, D95%, and D98% for the internal target volume (ITV) and the PTV. Two-tailed paired Student's t-tests determined the statistical significance. Although for most of the parameters evaluated, the mean differences observed between the AAA, AXB_Dm, and AXB_Dw were statistically significant (p < 0.05), absolute differences were rather small, in general less than 5% points. The maximum mean difference was observed in the ITV D50% between the AXB_Dm and the AAA and was 1.7% points under the isocenter prescription and 3.3% points under the D95 prescription. AXB_Dm produced higher values than AXB_Dw with differences ranging from 0.4 to 1.1% points under isocenter prescription and 0.0 to 0.7% points under the PTV D95% prescription. The differences observed under the PTV D95% prescription were larger compared to those observed for the isocenter prescription between AXB_Dm and AAA, AXB_Dm and AXB_Dw, and AXB_Dw and AAA. Although statistically significant, the mean differences between the three algorithms are within 3.3% points. PMID- 27685140 TI - Accuracy of one algorithm used to modify a planned DVH with data from actual dose delivery. AB - Detection and accurate quantification of treatment delivery errors is important in radiation therapy. This study aims to evaluate the accuracy of DVH based QA in quantifying delivery errors. Eighteen previously treated VMAT plans (prostate, H&N, and brain) were randomly chosen for this study. Conventional IMRT delivery QA was done with the ArcCHECK diode detector for error-free plans and plans with the following modifications: 1) induced monitor unit differences up to +/- 3.0%, 2) control point deletion (3, 5, and 8 control points were deleted for each arc), and 3) gantry angle shift (2 degrees uniform shift clockwise and counterclockwise). 2D and 3D distance-to-agreement (DTA) analyses were performed for all plans with SNC Patient software and 3DVH software, respectively. Subsequently, accuracy of the reconstructed DVH curves and DVH parameters in 3DVH software were analyzed for all selected cases using the plans in the Eclipse treatment planning system as standard. 3D DTA analysis for error-induced plans generally gave high pass rates, whereas the 2D evaluation seemed to be more sensitive to detecting delivery errors. The average differences for DVH parameters between each pair of Eclipse recalculation and 3DVH prediction were within 2% for all three types of error-induced treatment plans. This illustrates that 3DVH accurately quantifies delivery errors in terms of actual dose delivered to the patients. 2D DTA analysis should be routinely used for clinical evaluation. Any concerns or dose discrepancies should be further analyzed through DVH-based QA for clinically relevant results and confirmation of a conventional passing-rate-based QA. PMID- 27685139 TI - Thin-film CdTe detector for microdosimetric study of radiation dose enhancement at gold-tissue interface. AB - Presence of interfaces between high and low atomic number (Z) materials, often encountered in diagnostic imaging and radiation therapy, leads to radiation dose perturbation. It is characterized by a very narrow region of sharp dose enhancement at the interface. A rapid falloff of dose enhancement over a very short distance from the interface makes the experimental dosimetry nontrivial. We use an in-house-built inexpensive thin-film Cadmium Telluride (CdTe) photodetector to study this effect at the gold-tissue interface and verify our experimental results with Monte Carlo (MC) modeling. Three-micron thick thin-film CdTe photodetectors were fabricated in our lab. One-, ten- or one hundred-micron thick gold foils placed in a tissue-equivalent-phantom were irradiated with a clinical Ir-192 high-dose-rate (HDR) source and current measured with a CdTe detector in each case was compared with the current measured for all uniform tissue-equivalent phantom. Percentage signal enhancement (PSE) due to each gold foil was then compared against MC modeled percentage dose enhancement (PDE), obtained from the geometry mimicking the experimental setup. The experimental PSEs due to 1, 10, and 100 MUm thick gold foils at the closest measured distance of 12.5MUm from the interface were 42.6 +/- 10.8 , 137.0 +/- 11.9, and 203.0 +/- 15.4, respectively. The corresponding MC modeled PDEs were 38.1 +/- 1, 164 +/- 1, and 249 +/- 1, respectively. The experimental and MC modeled values showed a closer agreement at the larger distances from the interface. The dose enhancement in the vicinity of gold-tissue interface was successfully measured using an in house-built, high-resolution CdTe-based photodetector and validated with MC simulations. A close agreement between experimental and the MC modeled results shows that CdTe detector can be utilized for mapping interface dose distribution encountered in the application of ionizing radiation. PMID- 27685141 TI - Implementation of a double Gaussian source model for the BEAMnrc Monte Carlo code and its influence on small fields dose distributions. AB - The shape of the radiation source of a linac has a direct impact on the delivered dose distributions, especially in the case of small radiation fields. Traditionally, a single Gaussian source model is used to describe the electron beam hitting the target, although different studies have shown that the shape of the electron source can be better described by a mixed distribution consisting of two Gaussian components. Therefore, this study presents the implementation of a double Gaussian source model into the BEAMnrc Monte Carlo code. The impact of the double Gaussian source model for a 6 MV beam is assessed through the comparison of different dosimetric parameters calculated using a single Gaussian source, previously com-missioned, the new double Gaussian source model and measurements, performed with a diode detector in a water phantom. It was found that the new source can be easily implemented into the BEAMnrc code and that it improves the agreement between measurements and simulations for small radiation fields. The impact of the change in source shape becomes less important as the field size increases and for increasing distance of the collimators to the source, as expected. In particular, for radiation fields delivered using stereotactic collimators located at a distance of 59 cm from the source, it was found that the effect of the double Gaussian source on the calculated dose distributions is negligible, even for radiation fields smaller than 5 mm in diameter. Accurate determination of the shape of the radiation source allows us to improve the Monte Carlo modeling of the linac, especially for treatment modalities such as IMRT, were the radiation beams used could be very narrow, becoming more sensitive to the shape of the source. PMID- 27685142 TI - Simple quality assurance method of dynamic tumor tracking with the gimbaled linac system using a light field. AB - We proposed a simple visual method for evaluating the dynamic tumor tracking (DTT) accuracy of a gimbal mechanism using a light field. A single photon beam was set with a field size of 30 * 30 mm2 at a gantry angle of 90 degrees . The center of a cube phantom was set up at the isocenter of a motion table, and 4D modeling was performed based on the tumor and infrared (IR) marker motion. After 4D modeling, the cube phantom was replaced with a sheet of paper, which was placed perpen-dicularly, and a light field was projected on the sheet of paper. The light field was recorded using a web camera in a treatment room that was as dark as possible. Calculated images from each image obtained using the camera were summed to compose a total summation image. Sinusoidal motion sequences were produced by moving the phantom with a fixed amplitude of 20 mm and different breathing periods of 2, 4, 6, and 8 s. The light field was projected on the sheet of paper under three conditions: with the moving phantom and DTT based on the motion of the phantom, with the moving phantom and non-DTT, and with a stationary phantom for comparison. The values of tracking errors using the light field were 1.12 +/- 0.72, 0.31 +/- 0.19, 0.27 +/- 0.12, and 0.15 +/- 0.09 mm for breathing periods of 2, 4, 6, and 8s, respectively. The tracking accuracy showed dependence on the breath-ing period. We proposed a simple quality assurance (QA) process for the tracking accuracy of a gimbal mechanism system using a light field and web camera. Our method can assess the tracking accuracy using a light field without irradiation and clearly visualize distributions like film dosimetry. PMID- 27685143 TI - A methodology for on-board CBCT imaging dose using optically stimulated luminescence detectors. AB - Cone-beam computed tomography CBCT systems are used in radiation therapy for patient alignment and positioning. The CBCT imaging procedure for patient setup adds substantial radiation dose to patient's normal tissue. This study pre-sents a complete procedure for the CBCT dosimetry using the InLight optically stimulated-luminescence (OSL) nanoDots. We report five dose parameters: the mean slice dose (DMSD); the cone beam dose index (CBDIW); the mean volume dose (DMVD); point-dose profile, D(FOV); and the off-field Dose. In addition, CBCT skin doses for seven pelvic tumor patients are reported. CBCT-dose mea-surement was performed on a custom-made cylindrical acrylic body phantom (50cm length, 32cm diameter). We machined 25 circular disks (2 cm thick) with grooves and holes to hold OSL-nanoDots. OSLs that showed similar sensitivities were selected and calibrated against a Farmer-type ionization-chamber (0.6 CT) before being inserted into the grooves and holes. For the phantom scan, a standard CBCT imaging protocol (pelvic sites: 125 kVp, 80 mA and 25 ms) was used. Five dose parameters were quantified: DMSD, CBDIW, DMVD, D(FOV), and the off-field dose. The DMSD for the central slice was 31.1 +/- 0.85 mGy, and CBDIW was 34.5+/- 0.6 mGy at 16cm FOV. The DMVD was 25.6 +/- 1.1 mGy. The off-field dose was 10.5 mGy. For patients, the anterior and lateral skin doses attributable to CBCT imaging were 39.04 +/- 4.4 and 27.1 +/- 1.3 mGy, respectively.OSL nanoDots were convenient to use in measuring CBCT dose. The method of selecting the nanoDots greatly reduced uncertainty in the OSL measurements. Our detailed calibration procedure and CBCT dose measurements and calculations could prove useful in developing OSL routines for CBCT quality assessment, which in turn gives them the property of high spatial resolution, meaning that they have the potential for measurement of dose in regions of severe dose-gradients. PMID- 27685144 TI - Canadian Partnership for Quality Radiotherapy (CPQR) and the Canadian Organization of Medical Physicists (COMP) - Driving safety and quality assurance practice in Canada through the development of technical quality control guidelines. PMID- 27685145 TI - Erratum: Evaluation of the tool "Reg Refine" for user-guided deformable image registration. PMID- 27685146 TI - Embracing Progress: Thoughts on Open Access Publishing, the JACMP, and its $500 Article Publication Fee. PMID- 27685147 TI - Alexander P. Turner, PhD (1940-2016). PMID- 27685148 TI - Syndecan-4 Is an Independent Predictor of All-Cause as Well as Cardiovascular Mortality in Hemodialysis Patients. AB - BACKGROUND: Left ventricular hypertrophy is associated withincreased mortality in hemodialysis (HD) patients.Syndecan-4 plays a role in many processes that are involved in the heart fibrosis and hypertrophy.We designed this study to prospectively determine whether syndecan-4 was predictive of mortality in a group of HD patients. METHODS: In total, 191 HD patients were included. Clinical, biochemical and echocardiographic parameters were recorded. HD patients were followed-up for 23.18 +/- 4.02 months. RESULTS: Syndecan-4 levels correlated strongly with geometrical echocardiographic parameters and ejection fraction. Relations with pressure-related parameters were weak and only marginally significant. Using the receiver operating characteristics the optimal cut-off points in predicting all-cause as well as cardiovascular (CV) mortality were evaluated and patients were divided into low and high syndecan-4 groups. A Kaplan Meier analysis showed that the cumulative incidences of all-cause as well as CV mortality were higher in high serum syndecan-4 group compared with those with low serum syndecan-4 (p<0.001 in both cases).A multivariate Cox proportional hazards regression analysis revealed syndecan-4 concentration to be an independent and significant predictor of all-cause (hazard ratio, 2.99; confidence interval, 2.34 to 3.113; p<0.001)as well as CV mortality (hazard ratio, 2.81;confidence interval, 2.28to3.02; p<0.001). CONCLUSIONS: Serum syndecan-4 concentration reflects predominantly geometrical echocardiographic parameters. In HD patients serum syndecan-4 concentration is independently associated with all-cause as well as CV mortality. PMID- 27685149 TI - Classical Hodgkin lymphoma-type PTLD after solid organ transplantation in children: a report on 17 patients treated according to subsequent GPOH-HD treatment schedules. AB - Post-transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ transplantation (SOT). Classical Hodgkin lymphoma-type (HL-) PTLD is a rare subtype, and systematic data on treatment and prognosis are lacking. We report on 17 pediatric patients with classical HL-PTLD. HL-PTLD developed late at a median of 8.1 years after SOT. It was commonly EBV-positive (16/17) and expressed both CD30 (all tumors) and CD20 (8/17 tumors). Patients were treated with chemotherapy +/- involved field radiotherapy (IF-RT) according to the respective GPOH-HD protocol tailored by stage and LDH. Overall survival at 2 and 5 years was 86% with 81% of patients surviving event-free. Six patients had additional rituximab treatment; in two it was given as upfront monotherapy and in four was given concurrently with their chemotherapy. Rituximab monotherapy did not lead to long-term remission. In conclusion, treatment of HL-PTLD with classical HL chemotherapy is effective and tolerable. New treatment modalities such as CD30-targeted or EBV-specific agents may diminish toxicity. PMID- 27685151 TI - Ultrastrong Graphene-Based Fibers with Increased Elongation. AB - A new method to prepare graphene-based fibers with ultrahigh tensile strength, conductivity, and increased elongation is reported. It includes wet-spinning the mixture of GO aqueous dispersion with phenolic resin solution in a newly developed coagulation bath, followed by annealing. The introduced phenolic carbon increased densification of graphene fibers through reducing defects and increased interfacial interaction among graphene sheets by forming new C-C bonds, thus resulting in the increasing of stiffness, toughness, and conductivity simultaneously. PMID- 27685150 TI - Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model. AB - Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)-a serum protein mainly secreted by liver-was shown to inhibit oxidized low-density lipoprotein (OxLDL)/lipopolysaccharides (LPS)-induced inflammation in mouse macrophages. Additionally, MSP could reduce palmitic acid (PA)-induced lipid accumulation and lipogenesis in the HepG2 cell line. Altogether, these data suggest MSP as a suppressor for metabolic inflammation. However, so far the potential of MSP to be used as a treatment for NASH was not investigated. We hypothesized that MSP reduces lipid accumulation and hepatic inflammation. To investigate the effects of MSP in the early stage of NASH, low-density lipoprotein receptor (Ldlr-/-) mice were fed either a regular chow or a high fat, high cholesterol (HFC) diet for 7 days. Recombinant MSP or saline (control) was administrated to the mice by utilizing subcutaneously-implanted osmotic mini-pumps for the last 4 days. As expected, mice fed an HFC diet showed increased plasma and hepatic lipid accumulation, as well as enhanced hepatic inflammation, compared with chow-fed controls. Upon MSP administration, the rise in cholesterol and triglyceride levels after an HFC diet remained unaltered. Surprisingly, while hepatic macrophage and neutrophil infiltration was similar between the groups, MSP treated mice showed increased gene expression of pro-inflammatory and pro apoptotic mediators in the liver, compared with saline-treated controls. Contrary to our expectations, MSP did not ameliorate NASH. Observed changes in inflammatory gene expression suggest that further research is needed to clarify the long-term effects of MSP. PMID- 27685152 TI - Proficiency in Motivational Interviewing among Nurses in Child Health Services Following Workshop and Supervision with Systematic Feedback. AB - BACKGROUND: Research on training in motivational interviewing (MI) has shown eroding skills after workshops not followed by additional training input (supervision/coaching). There is a need for more research evaluating different types and lengths of post-workshop training with follow-up periods extending six months. This study is an extension of a previous evaluation of the level of proficiency in MI after workshop and four sessions of supervision among nurses in Swedish child health services. AIMS: To explore the level of MI proficiency among nurses participating in an intervention to prevent childhood obesity (n = 33), after receiving five additional sessions of supervision including feedback on observed practice, as well as level of proficiency at follow-up. METHODS: Level of proficiency was measured 4 and 12 months after completed supervision using recorded practice samples coded according to the Motivational Interviewing Treatment Integrity (MITI) Code. Potential predictors of outcome were investigated. RESULTS: Proficiency remained on the same levels after nine sessions of supervision as after four sessions, and was generally low. The percentage of nurses reaching the proficiency level ranged from 18.2 to 54.5% across indicators. MI-spirit had increased significantly at follow-up, and the rest of the indicators remained on the same levels. No predictors of outcome were found. CONCLUSIONS: Comprehensive training programs with prolonged post-workshop supervision and feedback on observed practice may help to sustain but not improve participants' proficiency in MI. Potential explanations to the results and suggestions for future research are discussed. PMID- 27685153 TI - Awe and scientific explanation. AB - Past research has established a relationship between awe and explanatory frameworks, such as religion. We extend this work, showing (a) the effects of awe on a separate source of explanation: attitudes toward science, and (b) how the effects of awe on attitudes toward scientific explanations depend on individual differences in theism. Across 3 studies, we find consistent support that awe decreases the perceived explanatory power of science for the theistic (Study 1 and 2) and mixed support that awe affects attitudes toward scientific explanations for the nontheistic (Study 3). (PsycINFO Database Record PMID- 27685154 TI - The impact of negative emotions on self-concept abstraction depends on accessible information processing styles. AB - Research suggests that anger promotes global, abstract processing whereas sadness and fear promote local, concrete processing (see Schwarz & Clore, 2007 for a review). Contrary to a large and influential body of work suggesting that specific affective experiences are tethered to specific cognitive outcomes, the affect-as-cognitive-feedback account maintains that affective experiences confer positive or negative value on currently dominant processing styles, and thus can lead to either global or local processing (Huntsinger, Isbell, & Clore, 2014). The current work extends this theoretical perspective by investigating the impact of discrete negative emotions on the self-concept. By experimentally manipulating information processing styles and discrete negative emotions that vary in appraisals of certainty, we demonstrate that the impact of discrete negative emotions on the spontaneous self-concept depends on accessible processing styles. When global processing was accessible, individuals in angry (negative, high certainty) states generated more abstract statements about themselves than individuals in either sad (Experiment 1) or fearful (Experiment 2; negative, low certainty) states. When local processing was made accessible, however, the opposite pattern emerged, whereby individuals in angry states generated fewer abstract statements than individuals in sad or fearful states. Together these studies provide new insights into the mechanisms through which discrete emotions influence cognition. In contrast to theories assuming a dedicated link between emotions and processing styles, these results suggest that discrete emotions provide feedback about accessible ways of thinking, and are consistent with recent evidence suggesting that the impact of affect on cognition is highly context-dependent. (PsycINFO Database Record PMID- 27685155 TI - Detecting transient emotional responses with improved self-report measures and instructions. AB - Psychological research often yields null results on self-reported emotion as measured by the Positive and Negative Affect Schedule (PANAS; Watson, Clark, & Tellegen, 1988), even when using manipulations that might intuitively be expected to be emotionally impactful. Three studies reported here support the hypothesis that changes in self-reported negative emotion may be detected more sensitively when discrete emotions are measured rather than by either PANAS NA or a measure created by combining discrete emotions, and when participants were instructed to report how they felt during an emotion-eliciting event versus how they felt afterward. In Study 1, emotion was manipulated with disgusting photographs, in Study 2, with recall of social exclusion/inclusion, and in Study 3, with reminders of personal mortality. Discussion focuses on implications for detecting emotional changes in psychological research, and the inadvisability of interpreting null results on an insensitive measure as indicating that emotional changes did not occur. (PsycINFO Database Record PMID- 27685156 TI - Generation of Two-color Antigen Microarrays for the Simultaneous Detection of IgG and IgM Autoantibodies. AB - Autoantibodies, which are antibodies against self-antigens, are present in many disease states and can serve as markers for disease activity. The levels of autoantibodies to specific antigens are typically detected with the enzyme-linked immunosorbent assay (ELISA) technique. However, screening for multiple autoantibodies with ELISA can be time-consuming and requires a large quantity of patient sample. The antigen microarray technique is an alternative method that can be used to screen for autoantibodies in a multiplex fashion. In this technique, antigens are arrayed onto specially coated microscope slides with a robotic microarrayer. The slides are probed with patient serum samples and subsequently fluorescent-labeled secondary antibodies are added to detect binding of serum autoantibodies to the antigens. The autoantibody reactivities are revealed and quantified by scanning the slides with a scanner that can detect fluorescent signals. Here we describe methods to generate custom antigen microarrays. Our current arrays are printed with 9 solid pins and can include up to 162 antigens spotted in duplicate. The arrays can be easily customized by changing the antigens in the source plate that is used by the microarrayer. We have developed a two-color secondary antibody detection scheme that can distinguish IgG and IgM reactivities on the same slide surface. The detection system has been optimized to study binding of human and murine autoantibodies. PMID- 27685157 TI - Studies on the probing stimulants for the white-backed planthopper, Sogatella furcifera (Homoptera: Delphacidae) in rice plant (Oryza sativa L.). AB - To elucidate the probing stimulants in rice plants for the white-backed planthopper, Sogatella furcifera, bioassay-guided separations were conducted, which led to the isolation of four active compounds. Using NMR and LC-MS spectra, their structures were determined as isoorientin 2"-O-(6'''-(E) feruloyl)glucoside, isoorientin 2"-O-(6'''-(E)-p-coumaroyl)glucoside, tricin 5-O glucoside, and isoscoparin 2"-O-(6'''-(E)-feruloyl)glucoside. PMID- 27685158 TI - Anticipated Notification of Sexual Partners following STD Diagnosis among Men Who Have Sex with Men and Transgender Women in Lima, Peru: A Mixed Methods Analysis. AB - BACKGROUND: New strategies to support partner notification (PN) are critical for STD control and require detailed understanding of how specific individual and partnership characteristics guide notification decisions. METHODS: From 2011 to 2012, 397 MSM and TW recently diagnosed with HIV, syphilis, or another STD completed a survey on anticipated notification of recent sexual partners and associated factors. Qualitative interviews were conducted with a subset of participants to provide further depth to quantitative findings. Prevalence ratios and generalized estimating equation (GEE) models were used to analyze participant and partner-level factors associated with anticipated PN. RESULTS: Among all partners reported, 52.5% were described as "Very Likely" or "Somewhat Likely" to be notified. Anticipated notification was more likely for main partners than casual (adjusted Prevalence Ratio [aPR], 95% CI: 0.63, 0.54-0.75) or commercial (aPR, 95% CI: 0.44, 0.31-0.62) partners. Other factors associated with likely notification included perception of the partner as an STD source (aPR, 95% CI: 1.27, 1.10-1.48) and anticipated future sexual contact with the partner (aPR, 95% CI: 1.30, 1.11-1.52). An HIV diagnosis was associated with a lower likelihood of notification than non-HIV STDs (aPR: 0.68, 0.55-0.86). Qualitative discussion of the barriers and incentives to PN reflected a similar differentiation of anticipated notification according to partnership type and type of HIV/STD diagnosis. DISCUSSION: Detailed attention to how partnership characteristics guide notification outcomes is essential to the development of new PN strategies. By accurately and thoroughly assessing the diversity of partnership interactions among individuals with HIV/STD, new notification techniques can be tailored to partner-specific circumstances. PMID- 27685160 TI - In Situ Impregnation of Silver Nanoclusters in Microporous Chitosan-PEG Membranes as an Antibacterial and Drug Delivery Percutaneous Device. AB - An in situ synthesis method for preparing silver nanoclusters (AgNCs) embedded in chitosan-polyethylene glycol (CS-PEG) membranes is disclosed. The aim is to develop implantable multifunctional devices for biofilm inhibition and drug release to reduce percutaneous device related complications (PDRCs). A multiple array of characterization techniques confirmed the formation of fluorescent AgNCs with sizes of ~3 nm uniformly distributed in CS-PEG matrix and their active role in determining the fraction and interconnectivity of the microporous membranes. The presence and increasing contents of AgNCs enhanced the mechanical stability of membranes and decreased their susceptibility to degradation in the presence of lysozyme and H2O2. Moreover, the presence and increasing concentrations of AgNCs hindered biofilm formation against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) and enabled a sustainable release of an anti-inflammatory drug naproxen in vitro until 24 h. The overall results gathered and reported in this work make the AgNCs impregnated CS-PEG membranes highly promising multifunctional devices combining efficient antibacterial activity and biocompatibility with active local drug delivery. PMID- 27685161 TI - Rationale for Embedded Musculoskeletal Care in Air Force Training and Operational Units. PMID- 27685159 TI - Tumor Infiltrating Lymphocytes Affect the Outcome of Patients with Operable Triple-Negative Breast Cancer in Combination with Mutated Amino Acid Classes. AB - BACKGROUND: Stromal tumor infiltrating lymphocytes (TILs) density is an outcome predictor in triple-negative breast cancer (TNBC). Herein we asked whether TILs are related to coding mutation load and to the chemical class of the resulting mutated amino acids, i.e., charged, polar, and hydrophobic mutations. METHODS: We examined paraffin tumors from TNBC patients who had been treated with adjuvant chemotherapy mostly within clinical trials (training cohort, N = 133; validation, N = 190) for phenotype concordance; TILs density; mutation load and types. RESULTS: Concordance of TNBC phenotypes was 42.1% upon local / central, and 72% upon central / central pathology assessment. TILs were not associated with mutation load, type and class of mutated amino acids. Polar and charged mutation patterns differed between TP53 and PIK3CA (p<0.001). Hydrophobic mutations predicted for early relapse in patients with high nodal burden and <50% TILs tumors (training: HR 3.03, 95%CI 1.11-8.29, p = 0.031; validation: HR 2.90, 95%CI 0.97-8.70, p = 0.057), especially if compared to patients with >50% TILs tumors (training p = 0.003; validation p = 0.015). CONCLUSIONS: TILs density is unrelated to mutation load in TNBC, which may be regarded as an unstable phenotype. If further validated, hydrophobic mutations along with TILs density may help identifying TNBC patients in higher risk for relapse. PMID- 27685162 TI - Developing a Salivary Antibody Multiplex Immunoassay to Measure Human Exposure to Environmental Pathogens. AB - The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. This manuscript describes the development and analysis of a bead-based multiplex immunoassay capable of measuring the presence of antibodies in human saliva to multiple pathogens simultaneously. Saliva is particularly attractive in this application because it is noninvasive, cheaper and easier to collect than serum. Antigens from environmental pathogens were coupled to carboxylated microspheres (beads) and used to measure antibodies in very small volumes of human saliva samples using a bead-based, solution-phase assay. Beads were coupled with antigens from Campylobacter jejuni, Helicobacter pylori, Toxoplasma gondii, noroviruses (G I.1 and G II.4) and hepatitis A virus. To ensure that the antigens were sufficiently coupled to the beads, coupling was confirmed using species specific, animal-derived primary capture antibodies, followed by incubation with biotinylated anti-species secondary detection antibodies and streptavidin-R phycoerythrin reporter (SAPE). As a control to measure non-specific binding, one bead set was treated identically to the others except it was not coupled to any antigen. The antigen-coupled and control beads were then incubated with prospectively-collected human saliva samples, measured on a high throughput analyzer based on the principles of flow cytometry, and the presence of antibodies to each antigen was measured in Median Fluorescence Intensity units (MFI). This multiplex immunoassay has a number of advantages, including more data with less sample; reduced costs and labor; and the ability to customize the assay to many targets of interest. Results indicate that the salivary multiplex immunoassay may be capable of identifying previous exposures and infections, which can be especially useful in surveillance studies involving large human populations. PMID- 27685163 TI - Dissemination and implementation science in program evaluation: A telemental health clinical consultation case example. AB - Increased attention has been placed on evaluating the extent to which clinical programs that support the behavioral health needs of youth have effective processes and result in improved patient outcomes. Several theoretical frameworks from dissemination and implementation (D&I) science have been put forth to guide the evaluation of behavioral health program implemented in the context of real world settings. Although a strong rationale for the integration of D&I science in program evaluation exists, few examples exist available to guide the evaluator in integrating D&I science in the planning and execution of evaluation activities. This paper seeks to inform program evaluation efforts by outlining two D&I frameworks and describing their integration in program evaluation design. Specifically, this paper seeks to support evaluation efforts by illustrating the use of these frameworks via a case example of a telemental health consultation program in pediatric primary care designed to improve access to behavioral health care for children and adolescents in rural settings. Lessons learned from this effort, as well as recommendations regarding the future evaluation of programs using D&I science to support behavioral health care in community-based settings are discussed. PMID- 27685164 TI - Validation of photographs usage to evaluate meat visual acceptability of young bulls finished in feedlot fed with or without essential oils. AB - Forty 1/2 Brown Swiss*1/2 Nellore crossbred bulls were distributed into three experimental groups: CON - diet without addition of essential oils; CLO - diet with average 5,000mg/animal/day of clove essential oils and CIN - diet with average 5,000mg/animal/day of cinnamon essential oils to evaluate three methodologies of visual acceptability: with steaks directly in Trays and Sequential and Random photos. Seventeen consumers evaluated visual appearance of meat using a 9-point structured hedonic scale. CON group presented higher shelf life than essential oils groups. Trays and Sequential scores were similar in the majority of days; thus digital images could be used to evaluate colour evolution. However, Random photos resulted in lower scores and slower acceptability decrease than Trays and Sequential photos (p<0.05) among the second and fifth day of display. Random photos presented a lower and more constant standard deviation than Trays and Sequential photos (p<0.01) indicating that this methodology promoted a higher standard situation for meat colour evaluation. PMID- 27685165 TI - Rapid Subtractive Patterning of Live Cell Layers with a Microfluidic Probe. AB - The microfluidic probe (MFP) facilitates performing local chemistry on biological substrates by confining nanoliter volumes of liquids. Using one particular implementation of the MFP, the hierarchical hydrodynamic flow confinement (hHFC), multiple liquids are simultaneously brought in contact with a substrate. Local chemical action and liquid shaping using the hHFC, is exploited to create cell patterns by locally lysing and removing cells. By utilizing the scanning ability of the MFP, user-defined patterns of cell monolayers are created. This protocol enables rapid, real-time and spatially controlled cell patterning, which can allow selective cell-cell and cell-matrix interaction studies. PMID- 27685166 TI - In Situ Monitoring of Diffusion of Guest Molecules in Porous Media Using Electron Paramagnetic Resonance Imaging. AB - A method is demonstrated to monitor macroscopic translational diffusion using electron paramagnetic resonance (EPR) imaging. A host-guest system with nitroxide spin probe 3-(2-Iodoacetamido)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (IPSL) as a guest inside the periodic mesoporous organosilica (PMO) aerogel UKON1-GEL as a host and ethanol as a solvent is used as an example to describe the protocol. Data is shown from a previous publication, where the protocol has been applied to both IPSL and Tris(8-carboxy-2,2,6,6-perdeutero-tetramethyl-benzo[1,2-d:4,5 d']bis(1,3)dithiole) methyl (Trityl) as guest molecules and UKON1-GEL and SILICA GEL as host systems. A method is shown to prepare aerogel samples that cannot be synthesized directly in the sample tube for measurement due to a size change during synthesis. The aerogel is attached to sample tubes using heat shrink tubing and a pressure cooker to reach the necessary temperature without evaporating the solvent in the process. The method does not assume a clearly defined initial distribution of guest molecules at the start of the measurement. Instead, it requires a reservoir on top of the aerogel and experimentally determines the influx rate during data analysis. The diffusion is monitored continually over a period of 20 hr by recording the 1d spin density profile within the sample. The spectrometer settings for the imaging experiment are described quantitatively. Data analysis software is provided to take the resonator sensitivity profile into account and to numerically solve the diffusion equation. The software determines the macroscopic translational diffusion coefficient by least square minimization of the difference between the experiment and the numerical solution of the diffusion equation. PMID- 27685168 TI - Strong Cooperative Spin Crossover in 2D and 3D FeII-MI,II Hofmann-Like Coordination Polymers Based on 2-Fluoropyrazine. AB - Self-assembling iron(II), 2-fluoropyrazine (Fpz), and [MII(CN)4]2- (MII = Ni, Pd, Pt) or [AuI(CN)2]- building blocks have afforded a new series of two- (2D) and three-dimensional (3D) Hofmann-like spin crossover (SCO) coordination polymers with strong cooperative magnetic, calorimetric, and optical properties. The iron(II) ions, lying on inversion centers, define elongated octahedrons equatorially surrounded by four equivalent centrosymmetric MU4-[MII(CN)4]2- groups. The axial positions are occupied by two terminal Fpz ligands affording significantly corrugated 2D layers {Fe(Fpz)2([MII(CN)4]}. The Pt and Pd derivatives undergo thermal- and light-induced SCO characterized by T1/2 temperatures centered at 155.5 and 116 K and hysteresis loops 22 K wide, while the Ni derivative is high spin at all temperatures, even at pressures of 0.7 GPa. The great stability of the high-spin state in the Ni derivative has tentatively been ascribed to the tight packing of the layers, which contrasts with that of Pt and Pd derivatives in the high- and low-spin states. The synthesis and structure of the 3D frameworks formulated {Fe(Fpz)[Pt(CN)4]}.1/2H2O and {Fe(Fpz)[Au(CN)2]2}, where Fpz acts as bridging ligand, which is also discussed. The former is high spin at all temperatures, while the latter displays very strong cooperative SCO centered at 243 K accompanied by a hysteresis loop 42.5 K wide. The crystal structures and SCO properties are compared with those of related complexes derived from pyrazine, 3-fluoropyridine, and pyridine. PMID- 27685167 TI - Hypoxia-activated prodrugs in the treatment of advanced pancreatic adenocarcinoma. AB - Pancreatic cancer is an aggressive malignancy with poor survival and high mortality rate with 250 000 deaths per year worldwide. The unique pancreatic cancer microenvironment serves as a major obstacle in the effective treatment of this malignancy. The microenvironment consists not only of pancreatic ductal adenocarcinoma cells but also comprises cells of pancreatic cancer stellate, vascular, and immune origin combined with a dense extracellular matrix containing collagen. The aforementioned pathology leads to an increased intratumor pressure combined with an erratic vascular proliferation within the tumor causing hypoxia and decreased drug delivery. This has led both scientists and clinicians to develop and study drugs with unique mechanisms of action to target the pancreatic cancer microenvironment. Herein, we discuss the pancreatic cancer hypoxic microenvironment, development of hypoxia-activated prodrugs, and results of trials utilizing those drugs to target pancreatic cancer. PMID- 27685169 TI - ? PMID- 27685170 TI - Leveraging Gibbs Ensemble Molecular Dynamics and Hybrid Monte Carlo/Molecular Dynamics for Efficient Study of Phase Equilibria. AB - We describe an extension of the Gibbs ensemble molecular dynamics (GEMD) method for studying phase equilibria. Our modifications to GEMD allow for direct control over particle transfer between phases and improve the method's numerical stability. Additionally, we found that the modified GEMD approach had advantages in computational efficiency in comparison to a hybrid Monte Carlo (MC)/MD Gibbs ensemble scheme in the context of the single component Lennard-Jones fluid. We note that this increase in computational efficiency does not compromise the close agreement of phase equilibrium results between the two methods. However, numerical instabilities in the GEMD scheme hamper GEMD's use near the critical point. We propose that the computationally efficient GEMD simulations can be used to map out the majority of the phase window, with hybrid MC/MD used as a follow up for conditions under which GEMD may be unstable (e.g., near-critical behavior). In this manner, we can capitalize on the contrasting strengths of these two methods to enable the efficient study of phase equilibria for systems that present challenges for a purely stochastic GEMC method, such as dense or low temperature systems, and/or those with complex molecular topologies. PMID- 27685171 TI - Analysis of the impact of a cognitive task on the posture of elderly subjects with depression compared with healthy elderly subjects. AB - OBJECTIVE: While previous studies have demonstrated that depressive elderly subjects (DES) experience difficulties in the processing of simultaneous cognitive tasks, few have examined the coupling of cognitive tasks with seemingly 'automatic' tasks, such as standing upright. Current patient management focuses on pharmacological treatments and cognitive-behavioral therapies. METHODS: Healthy elderly (HES) and non-treated DES were included. Postural sway in DES was compared with that in HES while in single-task and dual-task conditions. The single-task consisted of standing upright. For the dual-task, the subjects recalled various items from memory or counted while standing upright. Postural sway was evaluated by computing the center of pressure (CoP) area and path length. RESULTS: DES showed greater postural sway than HES in all conditions. The HES showed a greater CoP area in the dual-task than in the single-task conditions. In DES, the CoP area in the single-task condition was similar to that in the dual-task condition. CONCLUSIONS: The greater postural sway observed in DES may be a cause of a greater risk of falls. We showed that even seemingly automatic tasks, such as maintaining an upright posture, are affected by depression. SIGNIFICANCE: These results are important for the management of DES. PMID- 27685172 TI - Long Term Ex Vivo Culture and Live Imaging of Drosophila Larval Imaginal Discs. AB - Continuous imaging of live tissues provides clear temporal sequence of biological events. The Drosophila imaginal discs have been popular experimental subjects for the study of a wide variety of biological phenomena, but long term culture that allows normal development has not been satisfactory. Here we report a culture method that can sustain normal development for 18 hours and allows live imaging. The method is validated in multiple discs and for cell proliferation, differentiation and migration. However, it does not support disc growth and cannot support cell proliferation for more than 7 to 12 hr. We monitored the cellular behavior of retinal basal glia in the developing eye disc and found that distinct glia type has distinct properties of proliferation and migration. The live imaging provided direct proof that wrapping glia differentiated from existing glia after migrating to the anterior front, and unexpectedly found that they undergo endoreplication before wrapping axons, and their nuclei migrate up and down along the axons. UV-induced specific labeling of a single carpet glia also showed that the two carpet glia membrane do not overlap and suggests a tiling or repulsion mechanism between the two cells. These findings demonstrated the usefulness of an ex vivo culture method and live imaging. PMID- 27685173 TI - A driving simulator evaluation of potential speed reductions using two innovative designs for signalised urban intersections. AB - Intersections are typically associated with a higher level of crash risk than other types of facilities on the road network. Standard cross-road intersections are particularly hazardous because by their very design, drivers may travel through at speeds that are incompatible with human biomechanical tolerance should a crash occur. Further, drivers are exposed to dangerous conflict angles, which are likely to result in serious injury. This paper examines the effectiveness of two new intersection designs aimed at restricting potentially dangerous conflict angles while reducing driver speeds through the intersection. These designs, named the "Cut-Through" and the "Squircle", incorporate key features of both signalised intersections and roundabouts. The intersections are controlled by signals similar to a signalised roundabout. Instead of a standard central island, right turning traffic (equivalent to left turns in jurisdictions that drive on the right) cut through the central island, thereby avoiding traffic interlocks and delays that can occur with the traditional signalised roundabout. Across two driving simulator studies, vehicle speed data were collected on approach to and through each of the proposed intersection designs. Performance was benchmarked against equivalent standard signalised cross-road intersections and standard non signalised roundabouts. Notably, drivers reduced their speeds by approximately 30 40% when negotiating both the Cut-Through and the Squircle compared to the standard signalised intersections. The safety potentials of the two new intersection designs are discussed within the guidelines of the Safe Systems principles. PMID- 27685175 TI - Dehydrogenative Synthesis of Carboxylic Acids from Primary Alcohols and Hydroxide Catalyzed by a Ruthenium N-Heterocyclic Carbene Complex. AB - Primary alcohols have been reacted with hydroxide and the ruthenium complex [RuCl2(IiPr)(p-cymene)] to afford carboxylic acids and dihydrogen. The dehydrogenative reaction is performed in toluene, which allows for a simple isolation of the products by precipitation and extraction. The transformation can be applied to a range of benzylic and saturated aliphatic alcohols containing halide and (thio)ether substituents, while olefins and ester groups are not compatible with the reaction conditions. Benzylic alcohols undergo faster conversion than other substrates, and a competing Cannizzaro reaction is most likely involved in this case. The kinetic isotope effect was determined to be 0.67 using 1-butanol as the substrate. A plausible catalytic cycle was characterized by DFT/B3LYP-D3 and involved coordination of the alcohol to the metal, beta-hydride elimination, hydroxide attack on the coordinated aldehyde, and a second beta-hydride elimination to furnish the carboxylate. PMID- 27685174 TI - Individual employee's perceptions of " Group-level Safety Climate" (supervisor referenced) versus " Organization-level Safety Climate" (top management referenced): Associations with safety outcomes for lone workers. AB - Research has shown that safety climate is among the strongest predictors of safety behavior and safety outcomes in a variety of settings. Previous studies have established that safety climate is a multi-faceted construct referencing multiple levels of management within a company, most generally: the organization level (employee perceptions of top management's commitment to and prioritization of safety) and group level (employee perceptions of direct supervisor's commitment to and prioritization of safety). Yet, no research to date has examined the potential interaction between employees' organization-level safety climate (OSC) and group-level safety climate (GSC) perceptions. Furthermore, prior research has mainly focused on traditional work environments in which supervisors and workers interact in the same location throughout the day. Little research has been done to examine safety climate with regard to lone workers. The present study aims to address these gaps by examining the relationships between truck drivers' (as an example of lone workers) perceptions of OSC and GSC, both potential linear and non-linear relationships, and how these predict important safety outcomes. Participants were 8095 truck drivers from eight trucking companies in the United States with an average response rate of 44.8%. Results showed that employees' OSC and GSC perceptions are highly correlated (r= 0.78), but notable gaps between the two were observed for some truck drivers. Uniquely, both OSC and GSC scores were found to have curvilinear relationships with safe driving behavior, and both scores were equally predictive of safe driving behavior. Results also showed the two levels of climate significantly interacted with one another to predict safety behavior such that if either the OSC or GSC scores were low, the other's contribution to safety behavior became stronger. These findings suggest that OSC and GSC may function in a compensatory manner and promote safe driving behavior even when either OSC or GSC scores are low. The results of this study provide critical insight into the supplementary interaction between perceptions of OSC and GSC. Recommendations for future research, as well as practical recommendations for organizational intervention, are discussed. PMID- 27685176 TI - Ynamides as Racemization-Free Coupling Reagents for Amide and Peptide Synthesis. AB - A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH2, ArNH2, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis. PMID- 27685177 TI - Extraction and Analysis of Microbial Phospholipid Fatty Acids in Soils. AB - Phospholipid fatty acids (PLFAs) are key components of microbial cell membranes. The analysis of PLFAs extracted from soils can provide information about the overall structure of terrestrial microbial communities. PLFA profiling has been extensively used in a range of ecosystems as a biological index of overall soil quality, and as a quantitative indicator of soil response to land management and other environmental stressors. The standard method presented here outlines four key steps: 1. lipid extraction from soil samples with a single-phase chloroform mixture, 2. fractionation using solid phase extraction columns to isolate phospholipids from other extracted lipids, 3. methanolysis of phospholipids to produce fatty acid methyl esters (FAMEs), and 4. FAME analysis by capillary gas chromatography using a flame ionization detector (GC-FID). Two standards are used, including 1,2-dinonadecanoyl-sn-glycero-3-phosphocholine (PC(19:0/19:0)) to assess the overall recovery of the extraction method, and methyl decanoate (MeC10:0) as an internal standard (ISTD) for the GC analysis. PMID- 27685178 TI - Polymeric lipid vesicles with pH-responsive turning on-off membrane for programed delivery of insulin in GI tract. AB - A kind of polymeric lipid vesicles (PLVs) with pH-responsive turning on-off membrane for programed delivery of insulin in gastrointestinal (GI) tract was developed, which was self-assembled from the grafted amphipathic polymer of N tocopheryl-N'-succinyl-E-poly-l-lysine (TP/SC-g-PLL). By controlling the grafting ratio of hydrophobic alkane and ionizable carboxyl branches, the permeability of membrane was adjustable and thus allowing insulin release in a GI-pH dependent manner. The effects of grafting degree of substitution (DS) on the pH-responsive behavior of the formed vesicles were confirmed by critical aggregation concentration determination, morphology and size characterization. Their transepithelial permeability across the GI tract was proved by both confocal visualization in vitro model of Caco-2 cellular monolayer and in vivo hypoglycemic study in diabetic rats. Accordingly, the work described here indicated that the self-assembled PLVs could be a promising candidate for improving the GI delivery of hydrophilic biomacromolecule agents. PMID- 27685180 TI - Erratum: Vol. 65, No. 36. AB - In the report, "Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene - Connecticut, 2016," the Acknowledgments should have included the following: Alycia McNutt, David Santoro, Christina Nishimura, Diane Noel, Katherine A. Kelley Public Health Laboratory, Connecticut Department of Public Health. PMID- 27685179 TI - Adverse events in children and adolescents treated with quetiapine: an analysis of adverse drug reaction reports from the Danish Medicines Agency database. AB - Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported in the European Summary of Product Characteristics (SPCs). The ADE report database at Danish Medicines Agency was searched for all quetiapine ADRs involving individuals (<18 years) in the period 1997-2015. Fifteen ADE case reports were retrieved, scrutinized, and categorized. The average age was 14.8 years (range 10-17 years) and six patients were boys. The main reported ADEs were (i) endocrine, for example, hyperprolactinemia and hyperthyroidism, (ii) cardiac, for example, tachycardia and QT prolongation, (iii) neurological, for example, seizures and cerebral hemorrhage, and (iv) psychiatric, for example, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns. PMID- 27685181 TI - Bilateral Hypopyons as a Presenting Symptom. PMID- 27685182 TI - A Robust and Subject-Specific Hemodynamic Model of the Lower Limb Based on Noninvasive Arterial Measurements. AB - Cardiovascular diseases are currently the leading cause of mortality in the population of developed countries, due to the constant increase in cardiovascular risk factors, such as high blood pressure, cholesterol, overweight, tobacco use, lack of physical activity, etc. Numerous prospective and retrospective studies have shown that arterial stiffening is a relevant predictor of these diseases. Unfortunately, the arterial stiffness distribution across the human body is difficult to measure experimentally. We propose a numerical approach to determine the arterial stiffness distribution of an arterial network using a subject specific one-dimensional model. The proposed approach calibrates the optimal parameters of the reduced-order model, including the arterial stiffness, by solving an inverse problem associated with the noninvasive in vivo measurements. An uncertainty quantification analysis has also been carried out to measure the contribution of the model input parameters variability, alone or by interaction with other inputs, to the variation of clinically relevant hemodynamic indices, here the arterial pulse pressure. The results obtained for a lower limb model, demonstrate that the numerical approach presented here can provide a robust and subject-specific tool to the practitioner, allowing an early and reliable diagnosis of cardiovascular diseases based on a noninvasive clinical examination. PMID- 27685183 TI - Animal experimentation: Oh, when will they ever learn? PMID- 27685184 TI - Attitudes toward the use of animals in chronic versus acute pain research: results of a web-based forum. AB - When asked about the use of animals in biomedical research, people often state that the research is only acceptable if pain and distress are minimised. However, pain is caused when the aim is to study pain itself, resulting in unalleviated pain for many of the animals involved. Consequently, the use of animals in pain research is often considered contentious. To date, no research has explored people's views toward different types of animal-based pain research (e.g. chronic or acute pain). This study used a web-based survey to explore people's willingness to support the use of mice in chronic versus acute pain research. The majority of the participants opposed the use of mice for either chronic (68.3%) or acute (63.1%) pain research. There was no difference in the levels of support or opposition for chronic versus acute pain research. Unsupportive participants justified their opposition by focusing on the perceived lack of scientific merit, or the existence of non-animal alternatives. Supporters emphasised the potential benefits that could arise, with some stating that the benefits outweigh the costs. The majority of the participants were opposed to pain research involving mice, regardless of the nature and duration of the pain inflicted, or the perceived benefit of the research. A better understanding of public views toward animal use in pain research may provide a stronger foundation for the development of policy governing the use of animals in research where animals are likely to experience unalleviated pain. PMID- 27685185 TI - Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation. AB - The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study. In the alveolar space of the lung, epithelial cells and alveolar macrophages are the most important cell types, forming an efficient cellular barrier to aerosols. Our aim was to mimic this barrier with primary human alveolar cells. Cell densities of alveolar macrophages and epithelial cells, isolated from the same human donor, were optimised, with a focus on barrier properties. The combination of 300,000 epithelial cells/cm2 together with 100,000 macrophages/cm2 showed a functional barrier (transepithelial electrical resistance > 500Omega.cm2). This cell model was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures. The functionality of the in vitro system was investigated with spray-dried fluorescently labelled poly(lactic-co-glycolic) acid particles loaded with ovalbumin as a model drug. PMID- 27685186 TI - Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part II: evaluation of IL-10-loaded microparticles for the treatment of lung inflammation. AB - Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine. The inflammatory immune response was stimulated by lipopolysaccharide. The co-culture was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures )PADDOCC), to deposit the IL-10-loaded microparticles on the inflamed co-culture model at the air-liquid interface. This treatment significantly reduced the secretion of interleukin-6 and tumour necrosis factor, as compared to the deposition of placebo (unloaded) particles. Our results show that the alveolar co culture model, in combination with a deposition device such as the PADDOCC, may serve as a powerful tool for testing the safety and efficacy of dry powder formulations for pulmonary drug delivery. PMID- 27685188 TI - The European Citizens' Stop Vivisection Initiative and the revision of Directive. AB - Animal experimentation is presented to the public as an ongoing debate between research scientists on one hand, and the animal protection community on the other. An opportunity to break out of this mindset presented itself in the form of a European Citizens' Initiative, Stop Vivisection, which challenged Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals for scientific purposes. The manifesto of the initiative called upon the European Commission to replace the existing Directive with a new proposal that does away with animal experimentation, and instead makes compulsory the use of human data as a predictive modality for the study of human diseases and responses to drugs. Although the Initiative succeeded in gathering the required one million signatures, the European Commission ultimately rejected the proposal. However, some of the lessons learned from the Initiative may well be relevant to the revision of Directive 2010/63/EU, due to take place by 2017. PMID- 27685187 TI - Expectations for the methodology and translation of animal research: a survey of the general public, medical students and animal researchers in North America. AB - To determine what are considered acceptable standards for animal research (AR) methodology and translation rate to humans, a validated survey was sent to: a) a sample of the general public, via Sampling Survey International (SSI; Canada), Amazon Mechanical Turk (AMT; USA), a Canadian city festival (CF) and a Canadian children's hospital (CH); b) a sample of medical students (two first-year classes); and c) a sample of scientists (corresponding authors and academic paediatricians). There were 1379 responses from the general public sample (SSI, n = 557; AMT, n = 590; CF, n = 195; CH, n = 102), 205/330 (62%) medical student responses, and 23/323 (7%, too few to report) scientist responses. Asked about methodological quality, most of the general public and medical student respondents expect that: AR is of high quality (e.g. anaesthesia and analgesia are monitored, even overnight, and 'humane' euthanasia, optimal statistical design, comprehensive literature review, randomisation and blinding, are performed), and costs and difficulty are not acceptable justifications for lower quality (e.g. costs of expert consultation, or more laboratory staff). Asked about their expectations of translation to humans (of toxicity, carcinogenicity, teratogenicity and treatment findings), most expect translation more than 60% of the time. If translation occurred less than 20% of the time, a minority disagreed that this would "significantly reduce your support for AR". Medical students were more supportive of AR, even if translation occurred less than 20% of the time. Expectations for AR are much higher than empirical data show to have been achieved. PMID- 27685189 TI - Acute oral toxicity testing: Scientific evidence and practicability should govern Three Rs activities. AB - Acute oral toxicity is determined for regulatory hazard classification or non classification. The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) recommends the following modules for acute oral toxicity testing: a) the use of the in vitro 3T3 Neutral Red Uptake (NRU) test to identify substances not requiring classification and to estimate starting doses for in vivo acute oral toxicity studies; and b) the use of data from sub-acute toxicity studies to identify substances not requiring classification. However, the application of these modules in a regulatory context would require a predefined, validated and formally accepted testing strategy and data interpretation procedure, which are not available. Furthermore, the application of the 3T3 NRU assay for starting dose estimations could in fact increase the number of animals used. Finally, only very few substances exist for which data from sub-acute or other repeated dose studies are available, but data from acute studies are not. Therefore, in practice, the prediction of acute toxicity by using sub-acute toxicity data is generally irrelevant. It could even lead to a risk of overdosing in the range-finding study, which may result in the death of many or all of the animals used. PMID- 27685190 TI - Pathogenesis of ligaments ossification in spondyloarthritis: insights and doubts. AB - Despite intensive research in spondyloarthritis pathogenesis, some important questions still remain unanswered, particularly concerning enthesis new bone formation. Several evidences suggest that it prevalently occurs by endochondral ossification, however it remains to identify factors that can induce and influence its initiation and progression. Recent progress, achieved in animal models and in vitro and genetic association studies, has led us to hypothesize that several systemic factors (adipokines and gut hormones) and local factors (BMP and Wnt signaling) as well as angiogenesis and mechanical stress are involved. We critically review and summarize the available data and delineate the possible mechanisms involved in enthesis ossification, particularly at spinal ligament level. KEY MESSAGES Complete understanding of spondyloarthritis pathophysiology requires insights into inflammation, bone destruction and bone formation, which are all located in entheses and lead all together to ankylosis and functional disability. Several factors probably play a role in the pathogenesis of bone formation in entheses including not only cytokines but also several systemic factors such as adipokines and gut hormones, and local factors, such as BMP and Wnt signaling, as well as angiogenesis and mechanical stress. Data available about pathophysiology of new bone formation in spondyloarthritis are limited and often conflicting and future studies are needed to better delineate it and to develop new therapeutic approaches. PMID- 27685191 TI - Proper Emotion Recognition, Dysfunctional Emotion Regulation. AB - OBJECTIVE: A considerable number of adolescents exhibit severe self-regulation deficits in affect and behavior, which are referred to as affective dysregulation (AD). AD may be conceptualized as a dimensional trait that, in its extreme form, resembles the diagnostic categories of severe mood dysregulation (SMD) or disruptive mood dysregulation disorder (DMDD). Assuming a shared pathway of psychopathology in AD and SMD, similar underlying dysfunctional mechanisms in emotion processing, particularly emotion recognition (RECOG) and regulation (REGUL), may be postulated. METHOD: Adolescent inpatients with AD (CAD, N = 35), without AD (CCG, N = 28), and nonclinical controls (NCG; N = 28) were administered a morphed facial recognition task (RECOG). REGUL abilities, levels of irritability as well as depressive symptoms were also assessed. RESULTS: We found no significant group differences in accuracy and thresholds for RECOG abilities. Patients with AD reported more dysfunctional REGUL strategies than did CCG and NCG. Both depression and AD, but not irritability, influenced the overall degree of maladaptive REGUL. CONCLUSION: The broad phenotype of AD does not involve the deficits in RECOG reported for adolescents with a narrow phenotype (SMD); regarding REGUL strategies, AD seems to be associated with specific impairments. PMID- 27685193 TI - [Risk factors for self-injurious, aggressive, and stereotypic behavior in children and youths with visual impairments]. AB - Objective: To increase the limited knowledge concerning the form and risk factors of self-injurious, aggressive, and stereotypic behavior in children and youths with visual impairments. Method: Parents of 83 children and youths with visual impairments report on the characteristics of visual impairment, the social communicative competence of their children, and the frequency and severity of self-injurious, aggressive, and stereotypic behaviors. Results: Stereotypic behaviors are reported more often than the other behavioral abnormalities. The frequencies of stereotypic and self-injurious behaviors are correlated with each other. Children with higher social-communicative competence received lower scores in stereotypic and self-injurious behaviors (range of correlation coefficients between -.26 and -.48). Furthermore, the developmental delay of cognitive and adaptive competence is associated with the frequency and severity of these self injurious behaviors (F = 4.65, p = .012/F > 5.65, p < 0.01). For blind children, the parents describe a higher frequency and severity of stereotypic and self injurious behaviors. The frequency of self-injurious behavior is lower for children in an integrative setting. Conclusions: Frequency and severity of stereotypic and self-injurious behavior varies with characteristics of the child's visual impairment and additional disabilities. This association is not supported for aggressive behaviors. PMID- 27685192 TI - Emetophobia - A Metacognitive Therapeutic Approach for an Overlooked Disorder. AB - Objective: Emetophobia is the specific fear of vomiting that usually commences during childhood and adolescence. Cognitive behavioral therapy aims to expose patients to vomiting. In this paper, a newly developed metacognitive concept and treatment approach to this disorder is illustrated within a small case series. Methods: Three adolescent girls with emetophobia were treated with metacognitive therapy (MCT). Measures of anxiety, worry, depression, and metacognitions before and after the treatment were documented. Results: All patients recovered during the course of 8 to 11 sessions, and measurements of anxiety, worry, depression, and metacognitions dropped markedly. Conclusions: MCT presents a valuable treatment option for emetophobia in adolescents. PMID- 27685194 TI - Mild Hypothermia in a Child with Low-Dose Risperidone. AB - Risperidone is a widely used, second-generation antipsychotic approved for treating schizophrenia as well as for treating aggression in children and adolescents with mental retardation. The substance has a well-established risk profile including alterations of body temperature. Apart from hyperthermia with and without full-blown malignant neuroleptic syndrome, low body temperatures (hypothermia) have also been reported anecdotally, usually appearing in the context of comedication. Here, we report a case of hypothermia associated with a low-dose risperidone monotherapy in a child. PMID- 27685195 TI - Three-dimensional modeling of the cochlea by use of an arc fitting approach. AB - PURPOSE: A cochlea modeling approach is presented allowing for a user defined degree of geometry simplification which automatically adjusts to the patient specific anatomy. Model generation can be performed in a straightforward manner due to error estimation prior to the actual generation, thus minimizing modeling time. Therefore, the presented technique is well suited for a wide range of applications including finite element analyses where geometrical simplifications are often inevitable. METHODS: The method is presented for n=5 cochleae which were segmented using a custom software for increased accuracy. The linear basilar membrane cross sections are expanded to areas while the scalae contours are reconstructed by a predefined number of arc segments. Prior to model generation, geometrical errors are evaluated locally for each cross section as well as globally for the resulting models and their basal turn profiles. The final combination of all reconditioned features to a 3D volume is performed in Autodesk Inventor using the loft feature. RESULTS: Due to the volume generation based on cubic splines, low errors could be achieved even for low numbers of arc segments and provided cross sections, both of which correspond to a strong degree of model simplification. Model generation could be performed in a time efficient manner. CONCLUSION: The proposed simplification method was proven to be well suited for the helical cochlea geometry. The generated output data can be imported into commercial software tools for various analyses representing a time efficient way to create cochlea models optimally suited for the desired task. PMID- 27685197 TI - Follow-Up of Venom Immunotherapy on Flow Cytometry and Definition of a Protective Index. AB - BACKGROUND: A major problem of venom-specific immunotherapy (VIT) is the absence of reliable parameters for deciding treatment discontinuation. AIM OF THE STUDY: Intracutaneous tests (ICTs), the basophil activation test (BAT), specific IgEs (sIgEs) and blocking factor (BF) activity were measured during VIT. We made an evaluation by means of a protective index (PI) including ICT, BAT and BF values. MATERIAL AND METHODS: A population of 45 patients who had experienced a systemic reaction after an insect sting were tested before VIT (T0), at 1 week (T1w), at 10 weeks (T10w) and at 21 weeks (T21w), and, for a subgroup of 17 patients, at 3 5 years (T3-5y). Basophil activation (expressed in % CD63 and in the area under the curve) and BF activity were measured by flow cytometry using the CCR3/CD63 protocol. RESULTS: The first 21 weeks of follow-up showed no significant variation in the ICT, sIgE and BAT measurements, except for BAT, by eliminating weak negative anti-IgE responses. In these conditions, the decrease in basophil activation was significant at T10w (p = 0.009) and T21w (p = 0.009). Increased BF activity was also significant at T10w (p = 0.008) and T21w (p = 0.002). The PI threshold calculated from the mean +/- 3 standard errors (SE) was 64.8 (14.7 +/- 16.7, n = 25) at T0. PI increase was significant at T3-5y (3,430 +/- 6,282; p < 0.001). CONCLUSION: VIT induced a significant decrease in ICT values and basophil activation, along with an increase in serum BF activity, significant after 10 weeks of VIT. Evaluated in a larger population, the PI could represent a new tool for the clinico-biological follow-up of VIT efficacy. PMID- 27685198 TI - Cyclometalated Gold(III) Complexes: Synthesis, Reactivity, and Physicochemical Properties. AB - This Review showcases the ability of bi- and tridentate ligands to stabilize gold in high oxidation states through the formation of mono- and biscyclometalated gold(III) complexes. In-depth studies on the synthesis, intrinsic reactivity, catalytic relevance, and photophysical properties of stabilized gold(III) species have been carried out, setting the stage for exciting developments in various research areas, such as catalysis, inorganic and bioinorganic chemistry, ligand design, and materials science. PMID- 27685196 TI - Two-year follow-up of outcomes related to scarring and distress in children with severe burns. AB - PURPOSE: We assessed the perception of scarring and distress by pediatric burn survivors with burns covering more than one-third of total body surface area (TBSA) for up to 2 years post-burn. METHODS: Children with severe burns were admitted to our hospital between 2004 and 2012, and consented to this IRB approved-study. Subjects completed at least one Scars Problems and/or Distress questionnaire between discharge and 24 months post burn. Outcomes were modeled with generalized estimating equations or using mixed linear models. Significance was accepted at p < 0.01. RESULTS: Responses of 167 children with a mean age of 7 +/- 5 years and burns covering an average 54 +/- 14% of TBSA were analyzed. Significant improvements over the 2-year period were seen in reduction of pain, itching, sleeping disturbance, tightness, range of motion, and strength (p < 0.01). There was a significantly increased persistent desire to hide the scarred body areas over time (p < 0.01). The perception of mouth scarring, inability to portray accurate facial expressions, and skin coloration did not improve over the follow-up period. CONCLUSIONS: According to self-assessment questionnaires, severely burned children exhibit significant improvements in their overall perception of scarring and distress. However, these patients remain self conscious with respect to their body image even 2 years after burn injury. Implications for Rehabilitation According to self-assessment questionnaires, severely burned children perceive significant improvements in scarring and distress during the first 2 years post burn. Significant improvements were seen in reduction of pain, itching, sleeping disturbances, tightness, range of motion, and strength (p < 0.01). Burn care providers should improve the treatment of burns surrounding the mouth that with result in scarring, and develop strategies to prevent skin discoloration. Careful evaluation of pain and sleeping disorders during the first year post burn are warranted to improve the patient rehabilitation. Overall, significantly more female patients expressed a persistent desire to hide their scarred body areas. The rehabilitation team should provide access to wigs or other aids to pediatric burn survivors to address these needs. PMID- 27685199 TI - Steric-Structure-Dependent Gel Formation, Hierarchical Structures, Rheological Behavior, and Surface Wettability. AB - A series of bicholesteryl-based gelators with different central linker atoms C, N, and O (abbreviated to GC, GN, and GO, respectively) have been designed and synthesized. The self-assembly processes of these gelators were investigated by using gelation tests, field-emission scanning electron microscopy, field-emission transmission electron microscopy, UV/Vis absorption, IR spectroscopy, X-ray diffraction, rheology, and contact-angle experiments. The gelation ability, self assembly morphology, rheological, and surface-wettability properties of these gelators strongly depend on the central linker atom of the gelator molecule. Specifically, GC and GN can form gels in three different solvents, whereas GO can only form a gel in N,N-dimethylformamide (DMF). Morphologies from nanofibers and nanosheets to nanospheres and nanotubes can be obtained with different central atoms. Gels of GC, GN, and GO formed in the same solvent (DMF) have different tolerances to external forces. All xerogels gave a hydrophobic surface with contact angles that ranged from 121 to 152 degrees . Quantum-chemical calculations indicate that the GC, GN, and GO molecules have very different steric structures. The results demonstrate that the central linker atom can efficiently modulate the molecular steric structure and thus regulate the supramolecular self-assembly process and properties of gelators. PMID- 27685200 TI - ? AB - For most nurses, the complex system through which their pay and conditions are negotiated are of no consequence. They simply want a fair reward for their work. When they do not get it they are as capable as any group of venting their anger and frustration. Ultimately what concerns them is the environ- ment in which they work and the standard of care which they are able to deliver. But over the course of 1995, nurses have become increasingly aware of the consequences of inequitable pay systems and the dangers inherent in local pay determination. There is now a widely held belief among nurses that ' protecting the future of the Review Body is crucial to the profession's future I and its ability to carry out safe, effective nursing care. This week, however, the Nursing and Midwifery Staffs Negotiating Council could well make a decision contrary to those views. PMID- 27685201 TI - Midwives hold power balance in pay vote. AB - Nursing unions met yesterday in a bid to settle this year's pay dispute, with midwifery organisations seeming to hold the balance of power. PMID- 27685202 TI - The consensus statement. AB - 'We believe that the professional staff of the NHS arc a vital national resource. PMID- 27685203 TI - ? AB - Save Bart's Hospital campaigners, including nurses and other health staff, marched through Westminster last week as Parliament reconvened. PMID- 27685204 TI - Politicians blamed for creating local pay 'clamour'. AB - The move towards local pay is being driven by (politicians who want to be able to deny responsibility for nurses' wages being unfair, RCN director of labour relations Phil Gray claimed. PMID- 27685205 TI - Call for workforce planning as nurse shortage looms. AB - A national committee should be set up to oversee workforce planning for nursing, a leading academic researcher has argued. PMID- 27685206 TI - Nurse chief quizzed over college delays. AB - Scotland's chief nursing officer Anne Jarvie came under fire over delays in announcing which colleges will run nurse education in Scotland next year. PMID- 27685207 TI - ? AB - The Question Time panel, left to right: Nursing Standard editor Norah Casey; RCN general secretary Christine Hancock; the Rt. Rev. Richard Holloway, Bishop of Edinburgh; Scotland's chief nurse Anne Jarvie: Brian Potter from the BMA; and BBC Scotland's health correspondent Pennie Taylor. PMID- 27685208 TI - Council seeks better care access for prostitutes. AB - Prostitutes should have easy access to primary care services and should be able to disclose their occupation to health service providers, RCN Council agreed. PMID- 27685209 TI - 'End delay in nurse prescribing pilot results'. AB - RCN Council is to call on the National Health Service Executive to stop the 'unnecessary delay' in publishing the results of the nurse prescribing pilot projects. PMID- 27685210 TI - ? AB - Freemason Douglas Beattie (above) failed to become council chair at last week's meeting. He was defeated by 14 votes to nine by Pat Hughes. Sandra James was elected vice-chair and Jim McAllister was elected unopposed as honorary treasurer of the college. PMID- 27685211 TI - Call for more openness to silence the RCN gossips. AB - Royal College of Nursing general secretary Christine Hancock has called for openness in the RCN following press reports about Council members who are freemasons. PMID- 27685212 TI - Trust staff ready to be first into action. AB - Nurses at a Scottish mental health trust could be the first Royal College of Nursing members to take industrial action. PMID- 27685215 TI - UKCC deny slow progress on EN task force. AB - The UK Central Council has refuted claims it has acted unduly slowly in setting up a task force on the future of enrolled nurses. PMID- 27685214 TI - Anger over lack of warning on contraceptive pill advice. AB - Nurses slammed the government last week after it failed to give them adequate warning of a health department announcement that seven brands of the contraceptive pill increase the risk of blood clots. PMID- 27685216 TI - Scheme to help fund cost of older people living in residential care welcomed. AB - Nurses have welcomed government proposals, announced last week, to fund the nursing costs of older people living in private residential homes. PMID- 27685217 TI - Two Scottish nurses awarded fellowships for research. AB - Two Scottish nurses were awarded fellowships from the Royal College of Nursing last week for their outstanding contribution to nursing research. PMID- 27685218 TI - Slow uptake of RCN counselling by journalists at West murder trial. AB - Journalists in Winchester covering the Rosemary West trial have been slow to take up counselling offered to them by the Royal College of Nursing and Winchester & Eastleigh Healthcare NHS Trust. PMID- 27685219 TI - HVA to present Dorrell with paper on primary care. AB - A paper on the nurse's role in a primary care-led NHS is to be presented to health secretary Stephen Dorrell by the Health Visitors' Association. PMID- 27685221 TI - ? AB - The RCN has welcomed Labour's appointment of Harriet Hannan as shadow health secretary. RCN general secretary Christine Hancock said: 'The RCN has had a close working relationship with Harriet Harman for a number of years. She really understands and values the special contribution skilled nurses make to patient care.' Ms Harman said: 'I am looking forward to working with the doctors, nurses and many other health service workers who are holding this great public service together despite the Conservative government.' PMID- 27685222 TI - Nurse practitioners to take over GPs' nursing home work. AB - Nurse practitioners could soon be taking over GPs' work in nursing and residential homes, an RCN nurse managers' conference heard. PMID- 27685223 TI - NHS culture of 'presenteeism' is misguided. AB - Nursing managers are being drawn into working long hours by a misguided NHS culture of 'presenteeism', Glynis Markham of the NHS Women's Unit warned. PMID- 27685224 TI - Labour envisages health service with urban cottage hospitals run by nurses. AB - The future of the health service lies in urban cottage hospitals run by nurses in local communities, with GPs providing medical insight, Labour health spokesperson Tessa Jowell told the conference. PMID- 27685225 TI - Nurses' practical skills must not lose out to higher education, warns health minister. AB - Nursing must beware of abandoning its basic skills as it develops educationally, junior health minister Baroness Julia Cumberlege warned the RCN networking conference. PMID- 27685226 TI - Terbinafine for toe-nail tinea treatment. AB - Terbinafine is more effective than itraconazole in the treatment of toenail tinea, German researchers say. PMID- 27685227 TI - Influences on children's food choices. AB - Children associate'healthy' food with the concept of a proper meal and homemade foods, according to a researcher. PMID- 27685228 TI - Transdermal nicotine to reduce fibrinogen? AB - There is a possibility that transdermal nicotine might have a beneficial influence on cardiovascular risk factors, researchers say. PMID- 27685229 TI - The deal in detail. AB - If, as expected, the framework deal was approved by nursing unions yesterday, this is how it will work. PMID- 27685230 TI - Hypoglycaemia. AB - AIM AND INTENDED LEARNING OUTCOMES The aim of this article is to define hypoglycaemia and discuss its prevention and management in people with diabetes mellitus. After reading this article, the nurse should be able to: ? Define the aims of care for individuals with diabetes U Identify symptoms and causes of hypoglycaemia ? Suggest w'ays to prevent or minimise the risk of hypoglycaemia ? Treat hypoglycaemia effectively ? Educate patients regarding hypoglycaemia and identify when to involve the diabetes specialist nurse. PMID- 27685231 TI - Increased health problems at work. AB - I would like co make a few comments on, Research shows that shiftwork can damage your health' (Editorial October 11). PMID- 27685232 TI - Is stress counselling a waste of money? AB - I read in Nursing Standard (News October 11) that nurses who had witnessed the shooting of a patient were undergoing stress counselling. PMID- 27685233 TI - Good health care at a price. AB - There was furore and consternation recently at the comments made by Rodney Walker, outgoing chair of the NHS Trust Federation, that people should pay for their own health care. PMID- 27685234 TI - Ill-informed and inexperienced views. AB - At a recent meeting of the RCN Adolescent Special Interest Group, there was a feeling of dismay at the Reader's Panel discussion of where teenagers should be nursed (Viewpoint August 23). Given the background of the panel members, none of whom appeared to work directly with young people, it was difficult to see the point of the discussion. A more balanced discussion might have ensued if the selected panel had included paediatric nurses and those experienced in adolescent care. PMID- 27685235 TI - Free advice service from the RCN. AB - The feature on employment and work permits (No Limits October 18) clearly highlights the absurdity of rejecting a competent, professional and willing labour resource in the face of mounting evidence of nurse shortages. PMID- 27685236 TI - Patient welfare - not top priority. AB - As an independent community psychiatric nurse and co-manager of an independent CPN service in south and west Devon, I wets compelled to respond to your recently published article entitled 'Piggy in the middle' (Viewpoint October 11). PMID- 27685237 TI - Information exchange. AB - * The Multiple Sclerosis Society is undertaking a national investigation into the needs of the 85,000 people in the UK diagnosed with MS, their families and carers. PMID- 27685238 TI - Roll up, roll up. AB - Much has been written concerning the role of the healthcare assistant and the National Vocational Qualification in Direct Care ( 1 ). PMID- 27685240 TI - Know your rights. AB - Your contract of employment is the basis of many of your employment rights. It is the agreement you have with your employer setting out your terms and conditions of employment. PMID- 27685239 TI - Sell out of the century. AB - For the best part of two years I have been working in a nursing home- setting at healthcare assistant level. I am now a Project 2000 student. PMID- 27685241 TI - Mills & boon: reality or just romantic fantasy? AB - Our experts consider a hot topic of the day. PMID- 27685242 TI - Listings. AB - As there is such a huge demand for the publication of free listings, readers may wish to take advantage of a new service being launched by Nursing Standard. For further details see the coupon in the appointments section or contact Kim Bowdler, telephone 0181 423 1066. PMID- 27685243 TI - Increased social distance makes people more risk-neutral. AB - Individuals are consistently observed to be risk-averse over gains and risk seeking over losses. This study examined whether increased social distance would change these behavioral patterns. To test our hypothesis, social distance was manipulated by asking the participants to make decisions either for themselves or for another person (Experiment 1), either for a known person or for an unknown person (Experiment 2), and either for a close friend or for a distant friend (Experiment 3). The results of Experiments 1 and 3 showed that increased social distance made people more risk-neutral, and such an effect was stronger in the gain domain than in the loss domain. However, the effect of social distance was not observed in Experiment 2. These findings suggest that risk preferences are influenced by the social distance between decision makers and beneficiaries. PMID- 27685244 TI - The liminal self in people with multiple sclerosis: an interpretative phenomenological exploration of being diagnosed. AB - AIMS AND OBJECTIVES: To explore the lived experience of the meaning of being diagnosed with multiple sclerosis on the individual's sense of self. BACKGROUND: The time leading up to and immediately following the diagnosis of multiple sclerosis has been identified as a time period shrouded by uncertainty and one where individuals have a heightened desire to seek accurate information and support. The diagnosis brings changes to the way one views the self which has consequences for biographical construction. DESIGN: A hermeneutic phenomenological study. METHODS: In-depth qualitative interviews were conducted with 10 people recently diagnosed with multiple sclerosis. The data were analysed using interpretative phenomenological analysis. FINDINGS: This study presents the three master themes: the 'road to diagnosis', 'the liminal self' and 'learning to live with multiple sclerosis'. The diagnosis of multiple sclerosis may be conceptualised as a 'threshold moment' where the individual's sense of self is disrupted from the former taken-for-granted way of being and propose a framework which articulates the transition. CONCLUSION: The findings highlight the need for healthcare professionals to develop interventions to better support people affected by a new diagnosis of multiple sclerosis. The conceptual framework which has been developed from the data and presented in this study provides a new way of understanding the impact of the diagnosis on the individual's sense of self when affected by a new diagnosis of multiple sclerosis. This framework can guide healthcare professionals in the provision of supportive care around the time of diagnosis. RELEVANCE FOR CLINICAL PRACTICE: The findings provide practitioners with a new way of understanding the impact of the diagnosis on the individual's sense of self and a framework which can guide them in the provision of supportive care around the time of diagnosis. PMID- 27685245 TI - An Unusual Cause of Hematuria: Primary Bladder Melanoma in an Older Man. PMID- 27685246 TI - Essential Oils Composition and Antimicrobial Activity of Six Conifers Harvested in Lebanon. AB - The chemical composition and antimicrobial activity of the essential oils (EOs) of six conifers harvested in Lebanon, Abies cilicica, Cupressus sempervirens, Juniperus excelsa, Juniperus oxycedrus, Cedrus libani and Cupressus macrocarpa gold crest, were investigated. The EOs were obtained by hydrodistillation using a Clevenger-type apparatus and characterized by GC and GC/MS analyses. A principal components analysis based on Pearson correlation between essential oils chemical analyses was also conducted. The minimum inhibitory concentrations (MICs) of these essentials oils were determined against a range of bacteria and fungi responsible for cutaneous infections in human, using the broth microdilution technique. The EOs showed the most interesting bioactivity on the dermatophytes species (MIC values 32 - 64 MUg/ml). Each of the major compounds of C. macrocarpa as well as an artificial reconstructed EO were tested on Trichophyton rubrum showing a contribution of the minor components to the overall activity. PMID- 27685247 TI - Ni interferes in the Cu-regulated transcriptional switch petJ/petE in Synechocystis sp. PCC 6803. AB - Plastocyanin (petE) plays an essential role in photosynthesis as an electron carrier between cytochrome b6 f and photosystem I, and in some cyanobacteria it can be replaced by the haem-containing protein, cytochrome c6 (petJ). In Synechocystis sp. PCC 6803, transcription of petE and petJ is activated and repressed, respectively, by Cu. Here, we show that Ni can act similarly to Cu in inducing petE and repressing petJ, thus leading to a partial switch between cytochrome c6 and plastocyanin. Transcription of these genes is only altered by Ni in Cu-depleted medium, and none of the Ni-dependent transcription factors described in Synechocystis, NrsR and InrS seem to be involved in this regulation. Finally, we show that plastocyanin is essential for growth under conditions of excess Ni. PMID- 27685248 TI - Dermoscopy of small-size basal cell carcinoma: a case-control study. PMID- 27685249 TI - Screening sunscreens: protecting the biomechanical barrier function of skin from solar ultraviolet radiation damage. AB - OBJECTIVE: Solar ultraviolet (UV) radiation is ubiquitous in human life and well known to cause skin damage that can lead to harmful conditions such as erythema. Although sunscreen is a popular form of protection for some of these conditions, it is unclear whether sunscreen can maintain the mechanical barrier properties of skin. The objective of this study was to determine whether in vitro thin-film mechanical analysis techniques adapted for biological tissue are able to characterize the efficacy of commonly used UV inhibitors and commercial sunscreens to protect the biomechanical barrier properties of stratum corneum (SC) from UV exposure. METHODS: The biomechanical properties of SC samples were assayed through measurements of the SC's drying stress profile and delamination energy. The drying stresses within SC were characterized from the curvature of a borosilicate glass substrate onto which SC had been adhered. Delamination energies were characterized using a double-cantilever beam (DCB) cohesion testing method. Successive DCB specimens were prepared from previously separated specimens by adhering new substrates onto each side of the already tested specimen to probe delamination energies deeper into the SC. These properties of the SC were measured before and after UV exposure, both with and without sunscreens applied, to determine the role of sunscreen in preserving the barrier function of SC. RESULTS: The drying stress in SC starts increasing sooner and rises to a higher plateau stress value after UVA exposure as compared to non-UV exposed control specimens. For specimens that had sunscreen applied, the UVA exposed and non-UV-exposed SC had similar drying stress profiles. Additionally, specimens exposed to UVB without protection from sunscreen exhibited significantly lower delamination energies than non-UV-exposed controls. With commercial sunscreen applied, the delamination energy for UV-exposed and non-UV exposed tissue was consistent, even up to large doses of UVB. CONCLUSION: In vitro thin-film mechanical analysis techniques can readily characterize the effects of SC's exposure to UV radiation. The methods used in this study demonstrated commercial sunscreens were able to preserve the biomechanical properties of SC during UV exposure, thus indicating the barrier function of SC was also maintained. PMID- 27685250 TI - DNA methylation changes at SNCA intron 1 in patients with dementia with Lewy bodies. AB - AIM: It is difficult to diagnose dementia with Lewy bodies (DLB) because it exhibits clinical and neuropathological overlap with both Alzheimer's disease and Parkinson's disease. The alpha-synuclein protein is a major component of Lewy bodies, and accumulation of alpha-synuclein aggregates causes synaptic dysfunction in DLB. Epigenetic changes at the synuclein alpha ( SNCA ) gene may be involved in DLB pathogenesis. METHODS: We examined DNA methylation rates at 10 CpG sites located in intron 1 of SNCA and SNCA mRNA expression in peripheral leukocytes to compare DLB patients (n = 20; nine men, 11 women; age = 78.8 +/- 7.7 years) with healthy controls (n = 20; eight men, 12 women; age = 77.0 +/- 6.9 years). RESULTS: The methylation rate at CpG 4 ( P = 0.002) and the overall mean methylation rate at these sites (P < 0.001) were significantly lower in DLB patients than in healthy controls after Bonferroni correction. Although SNCA126 , a partial form of SNCA mRNA expression, was significantly increased in DLB ( P = 0.017), there was no significant difference in total SNCA mRNA expression between DLB patients and healthy controls ( P = 0.165). No correlation was observed between SCNA mRNA expression levels and blood DNA methylation rates in either DLB or healthy controls. CONCLUSION: Our findings indicated that lower methylation rates may be a biomarker for DLB. PMID- 27685251 TI - Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients. AB - : Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinemia, accounting for a mild increase of iron stores in insulin resistant subjects. Iron removal could improve insulin sensitivity. We performed a prospective, randomized, controlled trial (NCT01015525) in nondiabetic DIOS patients with hepatic iron >50 MUmol/g at magnetic resonance imaging to compare the metabolic and hepatic outcomes of 1-year maintenance of serum ferritin levels <50 MUg/L by bloodletting associated with lifestyle and diet advice (LFDA) to those of LFDA only. Patients were randomly assigned (1:1) with stratification by center (n = 8) and hyperglycemia (>5.6 mmol/L). Sample size was calculated to provide 90% power and a difference in fasting glycemia of 0.25 mmol/L. Analysis was done in an intention-to-treat population. In 2010-2014, 146 patients were randomly assigned to receive venesections with LFDA and 128 to LFDA only. At the end of the study, comparison of iron-depleted patients and controls showed ferritin levels 71 +/- 48 MUg/L after removal of 4.9 +/- 1.6 L of blood versus 733 +/- 277 MUg/L (P < 0.0001), glycemia 5.44 +/- 0.7 versus 5.49 +/- 0.7 mmol/L (P = 0.57), body weight +0.5 +/- 4.3% versus -0.6 +/- 3.3% (P = 0.03), homeostasis model of assessment of insulin resistance 3.39 versus 2.40 (P = 0.002), alanine aminotransaminase 33 +/- 22 versus 37 +/- 21 IU/L (P = 0.10), aspartate aminotransaminase 27 +/- 13 versus 27 +/- 10 IU/L (P = 0.81), gamma glutamyl transferase 54 +/- 138 versus 49 +/- 35 IU/L (P = 0.72), Fatty Liver Index 58.9 +/- 24.6 versus 61.2 +/- 22.9 (P = 0.37), and Fibrosis-4 score 1.5 +/- 0.6 versus 1.30 +/- 0.6 (P = 0.51). Fatigue occurred in 25.3% of venesected patients versus 2.3% of controls (P < 0.0001). In the subgroup of patients who lost weight, glycemia, homeostasis model of assessment of insulin resistance, serum ferritin, lipid profile, and liver function tests improved irrespective of bloodletting. CONCLUSION: In DIOS patients, iron depletion by bloodletting does not improve metabolic and hepatic features, is associated with weight gain, and is not as well tolerated as expected; sustained modification of diet and lifestyle habits remains the first therapeutic intervention in DIOS. (Hepatology 2017;65:465-474). PMID- 27685253 TI - Neuropsychology in Japan: history, current challenges, and future prospects. AB - OBJECTIVE: The purpose of this special issue was to describe the cross-cultural differences in neuropsychology throughout the world. The current state of neuropsychology in Japan is discussed in this manuscript. METHOD: Information on six topics, including (1) the history of Japanese neuropsychology, (2) licensure system, (3) job opportunities, (4) neuropsychological clinical services, (5) neuropsychological tests, and (6) neuropsychological research, was gathered via literature searches, official organization websites, and personal communication with clinical psychologists and other professionals in Japan. RESULTS: Neuropsychology reached Japan from the west in the late 1800s, a period of rapid political and social modernization. Professional associations were founded in the 1960s and 1970s and continued to grow. The need for neuropsychological assessment in Japan is growing; however, credential requirements for neuropsychologists have not yet been established. To practice clinical psychology in Japan, one must obtain a Master's degree and pass a licensure examination that is administered by a private professional foundation. Clinical psychologists often conduct neuropsychological tests; however, they have little training in neuropsychological assessment. While many western neuropsychological tests have been translated into Japanese and are used in clinical settings, the majority of translated tests have not been standardized and their psychometric properties remain poorly understood. Standardization and development of normative data in Japan is warranted. CONCLUSIONS: Given that needs for neuropsychological services are increasing, it is essential for clinical psychologists in Japan to improve their skills in neuropsychological evaluations. Japanese graduate schools must work to establish neuropsychology programs to educate and train clinical neuropsychologists. PMID- 27685254 TI - [Impulsivity-focused Group Intervention to reduce Binge Eating Episodes in Patients with Binge Eating Disorder - A Group Training Program]. AB - Binge Eating Disorder (BED) is an eating disorder where cognitive behavioural therapy (CBT) could already show reliable efficacy. Relying on basic research, CBT interventions which especially focus on impulsivity could be effective, because binge eating episodes represent highly impulsive eating behaviour. For this reason, we developed a treatment concept about an impulsivity-focused behavioural group intervention for patients with BED, called IMPULS. The efficacy of IMPULS is currently investigated in a randomised controlled trial 1. IMPULS is drafted as a weekly group training programme with 5-6 participants per group. The essential interventions are food-related cue exposure with response prevention and the development of self-control strategies. These interventions are adapted onto the impulsivity concept from conventional treatment of addictive disorders and BED. PMID- 27685252 TI - Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid. AB - Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH >=~12) sodium hypochlorite bleach, >=1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of >=103- to 106 fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of >=~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human alpha-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids. PMID- 27685255 TI - [Development and Validation of a Screening Instrument for Complex PTSD]. AB - Chronic interpersonal traumata systematically result in psychological impairments referred to as complex post-traumatic stress disorder (cPTSD or DESNOS). This diagnosis will be newly established in the ICD-11 system. However, there is need for diagnostic instruments to assess cPTSD. The aim was to develop a screening form to identify patients at risk for cPTSD. The Screening for complex PTSD (SkPTBS) tests a) experience of potential traumatic events, b) related influential features and risk factors, and c) symptoms of cPTSD. 325 patients (mean age 51.5+/-8.7 years; 62.1% female) filled out the screening instrument at the beginning of their inpatient psychotherapy. The primary criterion for testing SkPTBS validity was the diagnosis of complex PTSD at the end of the inpatient treatment. The proportion of patients with cPTSD was 8.9% (n=29). SkPTBS items were selective, and the scale showed very good reliability (alpha=0.91). Factor analysis revealed a one-dimensional structure. SkPTBS total values predicted having cPTSD diagnosis and were correlated with global symptom severity (SCL-90 R) and depressive symptoms (BDI-II). There is evidence for high clinical utility of SkPTBS. A revised version was developed. PMID- 27685256 TI - [Psychosocial Distress at Different Time Intervals after Burn Injury]. AB - Burn injuries can result in long-term mental and physical health problems. We investigated if patients at different time periods since the burn injury differed with regard to psychosocial impairment. Patients who were treated as inpatients because of burn injury between 2006 and 2012 were asked about quality of life (Burn Specific Health Scale - Brief; BSHS-B), anxiety and depression (Hospital Anxiety and Depression Scale - Deutsche Version; HADS-D), posttraumatic stress disorder (Impact of Event Scale - Revised; IES-R), stigmatization (Perceived Stigmatization Questionnaire; PSQ) and social support (Fragebogen zur sozialen Unterstutzung; F-SozU-7). The sample (146 patients) was divided into 4 groups according to the time period elapsed since the burn injury. There were no significant differences in psychosocial distress between the 4 groups. The same applied to sociodemographic and burn specific variables. 18 (12.4%) patients had the cutoff of >=11 for anxiety and 22 (15.2%) for depression on the HADS; 16 (11.1%) patients screened positive for posttraumatic stress disorder (PTSD). No differences were found for current psycho(pharmaco)therapy and the wish for psychotherapy. The results suggest persistence of psychosocial burden over time after burn injury. Psychosocial interventions might thus be indicated even many years after burn injuries. PMID- 27685258 TI - A Push-pull Protocol to Reduce Colonization of Bird Nest Boxes by Honey Bees. AB - Introduction of the invasive Africanized honey bee (AHB) into the Neotropics is a serious problem for many cavity nesting birds, specifically parrots. These bees select cavities that are suitable nest sites for birds, resulting in competition. The difficulty of removing bees and their defensive behavior makes a prevention protocol necessary. Here, we describe a push-pull integrated pest management protocol to deter bees from inhabiting bird boxes by applying a bird safe insecticide, permethrin, to repel bees from nest boxes, while simultaneously attracting them to pheromone-baited swarm traps. Shown here is an example experiment using Barn Owl nest boxes. This protocol successfully reduced colonization of Barn Owl nest boxes by Africanized honey bees. This protocol is flexible, allowing adjustments to accommodate a wide range of bird species and habitats. This protocol could benefit conservation efforts where AHB are located. PMID- 27685257 TI - Moderate Hypothermia Provides Better Protection of the Intestinal Barrier than Deep Hypothermia during Circulatory Arrest in a Piglet Model: A Microdialysis Study. AB - INTRODUCTION: This study aimed to assess the effects of different temperature settings of hypothermic circulatory arrest (HCA) on intestinal barrier function in a piglet model. METHODS: Twenty Wuzhishan piglets were randomly assigned to 40 min of HCA at 18 degrees C (DHCA group, n = 5), 40 min of HCA at 24 degrees C (MHCA group, n = 5), normothermic cardiopulmonary bypass (CPB group, n = 5) or sham operation (SO group, n = 5). Serum D-lactate (SDL) and lipopolysaccharide (LPS) levels were determined. Microdialysis parameters (glucose, lactate, pyruvate and glycerol) in the intestinal dialysate were measured. After 180 min of reperfusion, intestinal samples were harvested for real-time polymerase chain reaction and western blotting measurements for E-cadherin and Claudin-1. RESULTS: Higher levels of SDL and LPS were detected in the DHCA group than in the MHCA group (P < 0.001). Both MHCA and DHCA groups exhibited lower glucose levels, higher lactate and glycerol levels and a higher lactate to pyruvate (L/P) ratio compared with the CPB group (p<0.05); the DHCA group had higher lactate and glycerol levels and a higher L/P ratio (p<0.05) but similar glucose levels compared to the MHCA group. No significant differences in E-cadherin mRNA or protein levels were noted. Upregulation of claudin-1 mRNA levels was detected in both the DHCA and MHCA animals' intestines (P < 0.01), but only the DHCA group exhibited a decrease in claudin-1 protein expression (P < 0.01). CONCLUSION: HCA altered the energy metabolism and expression of epithelial junctions in the intestine. Moderate hypothermia (24 degrees C) was less detrimental to the markers of normal functioning of the intestinal barrier than deep hypothermia (18 degrees C). PMID- 27685260 TI - Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders. AB - Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human directed social behaviors have been found in laboratory beagles. Here, a Genome Wide Association Study identified two genomic regions associated with dog's human directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders. PMID- 27685263 TI - Biliary/Pancreas. PMID- 27685261 TI - Somalia: A Nation at the Crossroads of Extreme Poverty, Conflict, and Neglected Tropical Diseases. PMID- 27685259 TI - Multi-Center Evaluation of the Fully Automated PCR-Based IdyllaTM KRAS Mutation Assay for Rapid KRAS Mutation Status Determination on Formalin-Fixed Paraffin Embedded Tissue of Human Colorectal Cancer. AB - Since the advent of monoclonal antibodies against epidermal growth factor receptor (EGFR) in colorectal cancer therapy, the determination of RAS mutational status is needed for therapeutic decision-making. Most prevalent in colorectal cancer are KRAS exon 2 mutations (40% prevalence); lower prevalence is observed for KRAS exon 3 and 4 mutations (6%) and NRAS exon 2, 3, and 4 mutations (5%). The IdyllaTM KRAS Mutation Test on the molecular diagnostics IdyllaTM platform is a simple (<2 minutes hands-on time), highly reliable, and rapid (approximately 2 hours turnaround time) in vitro diagnostic sample-to-result solution. This test enables qualitative detection of 21 mutations in codons 12, 13, 59, 61, 117, and 146 of the KRAS oncogene being clinically relevant according to the latest clinical guidelines. Here, the performance of the IdyllaTM KRAS Mutation Assay, for Research Use Only, was assessed on archived formalin-fixed paraffin-embedded (FFPE) tissue sections by comparing its results with the results previously obtained by routine reference approaches for KRAS genotyping. In case of discordance, samples were assessed further by additional methods. Among the 374 colorectal cancer FFPE samples tested, the overall concordance between the IdyllaTM KRAS Mutation Assay and the confirmed reference routine test results was found to be 98.9%. The IdyllaTM KRAS Mutation Assay enabled detection of 5 additional KRAS-mutated samples not detected previously with reference methods. As conclusion the IdyllaTM KRAS Mutation Test can be applied as routine tool in any clinical setting, without needing molecular infrastructure or expertise, to guide the personalized treatment of colorectal cancer patients. PMID- 27685264 TI - Colorectal Cancer Prevention. PMID- 27685265 TI - Clinical Vignettes/Case Reports - Stomach. PMID- 27685262 TI - Specific Endocytosis Blockade of Trypanosoma cruzi Exposed to a Poly-LAcNAc Binding Lectin Suggests that Lectin-Sugar Interactions Participate to Receptor Mediated Endocytosis. AB - Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. This activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be delivered to reservosomes, the final lysosomal-like compartments. In African trypanosomes tomato lectin (TL) and ricin, respectively specific to poly-N-acetyllactosamine (poly-LacNAc) and beta-D-galactose, allowed the identification of giant chains of poly-LacNAc in N-glycoproteins of the endocytic pathway. We show that in T. cruzi epimastigote forms also, glycoproteins of the endocytic pathway are characterized by the presence of N linked glycans binding to both ricin and TL. Affinity chromatography using both TL and Griffonia simplicifolia lectin II (GSLII), specific to non-reducing terminal residue of N-acetylglucosamine (GlcNAc), led to an enrichment of glycoproteins of the trypanosomal endocytic pathway. Incubation of live parasites with TL, which selectively bound to the cytostome/cytopharynx, specifically inhibited endocytosis of transferrin (Tf) but not dextran, a marker of fluid endocytosis. Taken together, our data suggest that N-glycan modification of endocytic components plays a crucial role in receptor-mediated endocytosis of T. cruzi. PMID- 27685268 TI - Submitted, Not Presented: Biliary/Pancreas. PMID- 27685269 TI - Submitted, Not Presented: Colon. PMID- 27685271 TI - Submitted, Not Presented: Endoscopy. PMID- 27685270 TI - Submitted, Not Presented: Colorectal Cancer Prevention. PMID- 27685272 TI - Submitted, Not Presented: Endoscopy Video Forum. PMID- 27685273 TI - Submitted, Not Presented: Esophagus. PMID- 27685274 TI - Submitted, Not Presented: Functional Bowel Disease. PMID- 27685275 TI - Submitted, Not Presented: Inflammatory Bowel Disease. PMID- 27685276 TI - Submitted, Not Presented: Liver. PMID- 27685277 TI - Submitted, Not Presented: Outcomes Research. PMID- 27685278 TI - Submitted, Not Presented: Pediatrics. PMID- 27685279 TI - Submitted, Not Presented: Small Intestine/Unclassified. PMID- 27685280 TI - Submitted, Not Presented: Stomach. PMID- 27685281 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Biliary/Pancreas. PMID- 27685282 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Colon. PMID- 27685283 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Colorectal Cancer Prevention. PMID- 27685284 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Endoscopy. PMID- 27685285 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Esophagus. PMID- 27685286 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Functional Bowel Disease. PMID- 27685287 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Inflammatory Bowel Disease. PMID- 27685288 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Liver. PMID- 27685289 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Pediatrics. PMID- 27685290 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Small Intestine/Unclassified. PMID- 27685291 TI - Submitted, Not Presented: Clinical Vignettes/Case Reports - Stomach. PMID- 27685292 TI - Endoscopy. PMID- 27685293 TI - Endoscopy Video Forum. PMID- 27685294 TI - Esophagus. PMID- 27685297 TI - Liver. PMID- 27685295 TI - Functional Bowel Disease. PMID- 27685296 TI - Inflammatory Bowel Disease. PMID- 27685298 TI - Outcomes Research. PMID- 27685299 TI - Pediatrics. PMID- 27685300 TI - Small Intestine/Unclassified. PMID- 27685301 TI - Stomach. PMID- 27685302 TI - Clinical Vignettes/Case Reports - Biliary/Pancreas. PMID- 27685303 TI - Colon. PMID- 27685304 TI - Clinical Vignettes/Case Reports - Colon. PMID- 27685305 TI - Clinical Vignettes/Case Reports - Colorectal Cancer Prevention. PMID- 27685306 TI - Clinical Vignettes/Case Reports - Endoscopy. PMID- 27685308 TI - Clinical Vignettes/Case Reports - Functional Bowel Disease. PMID- 27685307 TI - Clinical Vignettes/Case Reports - Esophagus. PMID- 27685310 TI - Clinical Vignettes/Case Reports - Liver. PMID- 27685309 TI - Clinical Vignettes/Case Reports - Inflammatory Bowel Disease. PMID- 27685311 TI - Clinical Vignettes/Case Reports - Outcomes Research. PMID- 27685312 TI - Clinical Vignettes/Case Reports - Pediatrics. PMID- 27685313 TI - Clinical Vignettes/Case Reports - Small Intestine/Unclassified. PMID- 27685315 TI - Pharmacologic maintenance strategies following allogeneic hematopoietic cell transplantation for acute myeloid leukemia. AB - The use of pharmacologic agents to maintain remission following allogeneic hematopoietic cell transplantation (HCT) is a topic of increasing interest and exploration for patients with high-risk acute myeloid leukemia (AML). This review details published and ongoing studies focused on post-transplant pharmacologic maintenance for AML. While early phase studies have demonstrated the safety and tolerability of various maintenance approaches following HCT, the results of several ongoing randomized prospective studies will be required to determine the clinical efficacy needed to expand this approach from experimental to standard of care. PMID- 27685314 TI - Effect of an Antibacterial Monomer on the Antibacterial Activity of a Pit-and Fissure Sealant. AB - Resin-based pit-and-fissure sealants are often used to form a barrier on the occlusal surface of molars to treat caries lesions; however, bacteria can remain in the pit and fissures without detection, increasing the risk of secondary caries. Sealants with antimicrobial properties or microbial repellent actions might be advantageous. The aim of this study was to assess the inhibitory effect of a 2-methacryloxylethyl dodecyl methyl ammonium bromide (MAE-DB)-incorporated sealant against Streptococcus mutans. MAE-DB (4% wt) was incorporated into a commercially available sealant, Eco-S resin-based pit-and-fissure sealant (Vericom Co., Ltd., Korea); a sealant without MAE-DB served as a negative control, and ClinproTM Sealant (3MTM ESPETM), a fluoride-releasing resin, was used as a commercial control. The effects of the cured sealants and their eluents on the growth of S. mutans were determined according to colony-forming unit counts and metabolic tests. The effects of the cured sealants on the adherence and membrane integrity of S. mutans were investigated using confocal laser scanning microscopy (CLSM) in conjunction with fluorescent indicators. Compared with the negative control and commercial control, the cured MAE-DB-incorporated pit-and-fissure sealant exhibited a significant inhibitory effect on the growth of S. mutans (P < 0.05), whereas the eluents did not show any detectable antibacterial activity. The commercial control also showed no detectable bactericidal activity. Moreover, the aged experimental material retained its property of contact inhibition of biofilm formation. The fluorescence analysis of CLSM images demonstrated that the cured MAE-DB-incorporated sealant could hamper the adherence of S. mutans and exert a detrimental effect on bacterial membrane integrity. The incorporation of MAE-DB can render a pit-and-fissure sealant with contact antibacterial activity after polymerization via influencing the growth, adherence, and membrane integrity of S. mutans. Therefore, MAE-DB-containing pit and-fissure sealant shows promise for preventing or controlling dental caries on occlusal pit and fissures of molars. PMID- 27685316 TI - Long-Term Storage at -80 degrees C: Effect on Rate of Recovery of Mycobacterium tuberculosis From Direct Acid-Fast Bacilli Smear-Positive Sputum Samples. AB - BACKGROUND: The aim of this study was to evaluate the difference in the rate of recovery of Mycobacterium tuberculosis (MTB) from routinely cultured sputum and long-term stored sputum specimens (at -80 degrees C) using Lowenstein-Jensen (LJ) media, Mycobacterium Growth Indicator Tube (BBL MGIT(TM) ), and Middlebrook 7H11 (MB 7H11) agar. METHODS: Direct acid-fast bacilli smear-positive sputum specimens (both before and after storage [n = 136]) were studied (after culturing on LJ media, BBL MGIT(TM) , and MB 7H11 agar) and the performances were compared. RESULTS: For the detection of MTB, BBL MGIT(TM) and MB 7H11 agar (before storage) demonstrated a sensitivity, specificity, positive predictive value (PPV) of 98.28%, 30.77%, 92.68%, 66.67%, and negative predictive value (NPV) of 97.41%, 30.77%, 92.62%, 57.14%, respectively, when compared to LJ media (before storage). Similarly, BBL MGIT(TM) and MB 7H11 agar (after storage) demonstrated a sensitivity, specificity, PPV, and NPV of 95.5%, 38.89%, 90.6%, 58.33%, and 95.5%, 66.67 %, 94.64%, 70.59%, respectively, when compared to LJ media (after storage) for the detection of MTB. CONCLUSION: None of the culture techniques independently (both before and after storage) detected growth of MTB from all the sputum specimens studied. However, BBL MGIT(TM) system and LJ media combination (both before and after storage) effectively detected the growth of MTB from sputum specimens when compared to other culture technique combinations. PMID- 27685317 TI - Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans. AB - When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs. PMID- 27685318 TI - Diphosphine-Protected Au22 Nanoclusters on Oxide Supports Are Active for Gas Phase Catalysis without Ligand Removal. AB - Investigation of atomically precise Au nanoclusters provides a route to understand the roles of coordination, size, and ligand effects on Au catalysis. Herein, we explored the catalytic behavior of a newly synthesized Au22(L8)6 nanocluster (L = 1,8-bis(diphenylphosphino) octane) with in situ uncoordinated Au sites supported on TiO2, CeO2, and Al2O3. Stability of the supported Au22 nanoclusters was probed structurally by in situ extended X-ray absorption fine structure (EXAFS) and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), and their ability to adsorb and oxidize CO was investigated by IR absorption spectroscopy and a temperature-programmed flow reaction. Low-temperature CO oxidation activity was observed for the supported pristine Au22(L8)6 nanoclusters without ligand removal. Density functional theory (DFT) calculations confirmed that the eight uncoordinated Au sites in the intact Au22(L8)6 nanoclusters can chemisorb both CO and O2. Use of isotopically labeled O2 demonstrated that the reaction pathway occurs mainly through a redox mechanism, consistent with the observed support-dependent activity trend of CeO2 > TiO2 > Al2O3. We conclude that the uncoordinated Au sites in the intact Au22(L8)6 nanoclusters are capable of adsorbing CO, activating O2, and catalyzing CO oxidation reaction. This work is the first clear demonstration of a ligand protected intact Au nanocluster that is active for gas-phase catalysis without the need of ligand removal. PMID- 27685319 TI - Achieving competencies in family medicine through continuing professional development. PMID- 27685321 TI - Couples coping with cardiovascular disease: A systematic review. AB - INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death for both men and women. Its potential ramifications on all aspects of life, for patients and partners, are just beginning to be understood. Although research has focused on the individual who has received the diagnosis, relatively little is known about how couples manage CVD. This article presents a systematic review of literature that focuses on how couples cope with one partner's CVD diagnosis. A systematic review is warranted to orient practitioners, policy makers, and researchers to the state of existing knowledge and its gaps and to identify what still needs to be done. METHOD: Data were extracted from 25 peer-reviewed articles that met our inclusion criteria. Content examined included theory integration, coping constructs and instruments, samples, analyses, and findings. RESULTS: Most articles successfully integrated theory in the studies' respective conceptualizations and designs. Most used valid and reliable instruments to measure coping. Principal limitations included problematic sampling strategies and analysis techniques, thereby limiting external validity. DISCUSSION: Principal implications of this review's findings relate to our fields' need to provide more care focused on dyads (vs. individual patients), adopt an integrated model in health care, and conduct systemic, longitudinal research to gain a better grasp on how coping changes over time. Doing so will serve to better equip providers in the support of patients and partners living with CVD. (PsycINFO Database Record PMID- 27685320 TI - Quantitative Structure Activity Relationship Models for the Antioxidant Activity of Polysaccharides. AB - In this study, quantitative structure activity relationship (QSAR) models for the antioxidant activity of polysaccharides were developed with 50% effective concentration (EC50) as the dependent variable. To establish optimum QSAR models, multiple linear regressions (MLR), support vector machines (SVM) and artificial neural networks (ANN) were used, and 11 molecular descriptors were selected. The optimum QSAR model for predicting EC50 of DPPH-scavenging activity consisted of four major descriptors. MLR model gave EC50 = 0.033Ara-0.041GalA-0.03GlcA 0.025PC+0.484, and MLR fitted the training set with R = 0.807. ANN model gave the improvement of training set (R = 0.96, RMSE = 0.018) and test set (R = 0.933, RMSE = 0.055) which indicated that it was more accurately than SVM and MLR models for predicting the DPPH-scavenging activity of polysaccharides. 67 compounds were used for predicting EC50 of the hydroxyl radicals scavenging activity of polysaccharides. MLR model gave EC50 = 0.12PC+0.083Fuc+0.013Rha-0.02UA+0.372. A comparison of results from models indicated that ANN model (R = 0.944, RMSE = 0.119) was also the best one for predicting the hydroxyl radicals scavenging activity of polysaccharides. MLR and ANN models showed that Ara and GalA appeared critical in determining EC50 of DPPH-scavenging activity, and Fuc, Rha, uronic acid and protein content had a great effect on the hydroxyl radicals scavenging activity of polysaccharides. The antioxidant activity of polysaccharide usually was high in MW range of 4000-100000, and the antioxidant activity could be affected simultaneously by other polysaccharide properties, such as uronic acid and Ara. PMID- 27685322 TI - Deficits awareness in persons with mild cognitive impairment and family care partners. AB - INTRODUCTION: An emerging perspective of dyadic coping with chronic illness argues that concordance in the appraisal of illness is crucial for collaborative attempts at seeking information, making treatment decisions, and planning for long-term management of the illness and psychological and physical adjustments of both the care provider and care recipient. The present study examined whether persons with mild cognitive impairment (PwMCIs) and their family care partners (CPs) exhibited concordance in their awareness of deficits in the PwMCIs. Furthermore, this study explored the differences in concordance based on the relationship of the informant to the PwMCI, specifically spouse CP (SCP) versus adult child CP (ACCP). METHOD: PwMCI-SCP pairs (n = 55) and PwMCI-ACCP (n = 14) pairs provided reports on their awareness of PwMCI's functional and cognitive deficits. CPs also reported their knowledge about dementia. RESULTS: SCPs, but not ACCPs, reported greater deficits in everyday activity than PwMCIs' self reports. Additionally, compared to SCPs, ACCPs had more accurate knowledge about dementia, and their perception of PwMCI deficits corresponded more closely to PwMCI's self-perception. DISCUSSION: These findings demonstrate that concordance in awareness of PwMCI deficits varies across functional and cognitive areas and types of dyads. The results also highlight the importance of mild cognitive impairment-related education and support programs for care dyads to strengthen concordance, which is likely an important underpinning for effective coping as the illness progresses. (PsycINFO Database Record PMID- 27685323 TI - Antibody Labeling with Fluorescent Dyes Using Magnetic Protein A and Protein G Beads. AB - Antibodies labeled with small molecules like fluorescent dyes, cytotoxic drugs, and radioactive tracers are essential tools in biomedical research, immunodiagnostics and more recently as therapeutic agents. Traditional methods for labeling antibodies with small molecules require purified antibodies at relatively high concentration, involve multiple dialysis steps and have limited throughput. However, several applications, including the field of Antibody Drug Conjugates (ADCs), will benefit from new methods that will allow labeling of antibodies directly from cell media. Such methods may allow antibodies to be screened in biologically relevant assays, for example, the receptor-mediated antibody internalization assay in the case of ADCs. Here, we describe a method (on-bead method) that enables labeling of small amounts of antibodies directly from cell media. This approach utilizes high capacity magnetic Protein A and Protein G affinity beads to capture antibodies from the cell media followed by labeling with small molecules using either amine or thiol chemistry and subsequent elution of the labeled antibodies. Taking fluorescent dyes as surrogates for small molecules, we demonstrate the on-bead labeling of three different mouse antibodies directly from cell media using both amine and thiol labeling chemistry. The high binding affinity of antibodies to Protein A and Protein G ensures high recoveries as well as high purity of the labeled antibodies. In addition, use of magnetic beads allows multiple samples to be handled manually, thereby significantly improving labeling throughput. PMID- 27685324 TI - Enzymatic activity of cell-free extracts from Burkholderia oxyphila OX-01 bio converts (+)-catechin and (-)-epicatechin to (+)-taxifolin. AB - This study characterized the enzymatic ability of a cell-free extract from an acidophilic (+)-catechin degrader Burkholderia oxyphila (OX-01). The crude OX-01 extracts were able to transform (+)-catechin and (-)-epicatechin into (+) taxifolin via a leucocyanidin intermediate in a two-step oxidation. Enzymatic oxidation at the C-4 position was carried out anaerobically using H2O as an oxygen donor. The C-4 oxidation occurred only in the presence of the 2R-catechin stereoisomer, with the C-3 stereoisomer not affecting the reaction. These results suggest that the OX-01 may have evolved to target both (+)-catechin and (-) epicatechin, which are major structural units in plants. PMID- 27685325 TI - Associations of Novel and Traditional Vascular Biomarkers of Arterial Stiffness: Results of the SAPALDIA 3 Cohort Study. AB - BACKGROUND AND OBJECTIVES: There is a lack of evidence concerning associations between novel parameters of arterial stiffness as cardiovascular risk markers and traditional structural and functional vascular biomarkers in a population-based Caucasian cohort. We examined these associations in the second follow-up of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA 3). METHODS: Arterial stiffness was measured oscillometrically by pulse wave analysis to derive the cardio-ankle vascular index (CAVI), brachial-ankle (baPWV) and aortic pulse wave velocity (aPWV), and amplitude of the forward and backward wave. Carotid ultrasonography was used to measure carotid intima-media thickness (cIMT) and carotid lumen diameter (LD), and to derive a distensibility coefficient (DC). We used multivariable linear regression models adjusted for several potential confounders for 2,733 people aged 50-81 years. RESULTS: CAVI, aPWV and the amplitude of the forward and backward wave were significant predictors of cIMT (p < 0.001). All parameters were significantly associated with LD (p < 0.001), with aPWV and the amplitude of the forward wave explaining the highest proportion of variance (2%). Only CAVI and baPWV were significant predictors of DC (p < 0.001), explaining more than 0.3% of the DC variance. CONCLUSION: We demonstrated that novel non-invasive oscillometric arterial stiffness parameters are differentially associated with specific established structural and functional local stiffness parameters. Longitudinal studies are needed to follow-up on these cross-sectional findings and to evaluate their relevance for clinical phenotypes. PMID- 27685327 TI - Zirconium-Catalyzed Asymmetric Carboalumination of Unactivated Terminal Alkenes. AB - Carbometalation of alkenes with stereocontrol offers an important opportunity for asymmetric C-C bond formation. However, the scope of catalytic stereoselective carbometalation of alkenes had until recently been limited to electronically biased alkenes or those with the presence of directing groups or other auxiliary functionalities to overcome the challenge associated with regio- and stereoselectivity. Catalytic asymmetric carbometalation of unactivated alkenes on the other hand remained as a formidable challenge. To address this long-standing problem, we sought to develop Zr-catalyzed asymmetric carboalumination of alkenes (namely, ZACA reaction) encouraged by our discovery of Zr-catalyzed alkyne carboalumination in 1978. Zr-catalyzed methylalumination of alkynes (ZMA) shows high regioselectivity and nearly perfect stereoselectivity. Its mechanistic studies have revealed that the ZMA reaction involves acyclic carbometalation with "superacidic" bimetallic reagents generated by interaction between two Lewis acids, i.e., alkylalanes and 16-electron zirconocene derivatives through dynamic polarization and ate complexation, affectionately termed as the "two-is-better than-one" principle. With the encouraging results of Zr-catalyzed carboalumination of alkynes in hand, we sought to develop its alkene version for discovering a catalytic asymmetric C-C bond-forming reaction by using alkylalanes and suitable chiral zirconocene derivatives, which would generate "superacidic" bimetallic species to promote the desired carbometalation of alkenes. However, this proved to be quite challenging. Three major competing side reactions occur, i.e., (i) beta-H transfer hydrometalation, (ii) bimetallic cyclic carbometalation, and (iii) Ziegler-Natta polymerization. The ZACA reaction was finally discovered by employing Erker's (-)-(NMI)2ZrCl2 as the catalyst and chlorinated hydrocarbon as solvent to suppress the undesired side reactions mentioned above. The ZACA reaction has evolved as a powerful tool for the efficient preparation of a wide range of chiral natural products through the following methodological developments: (1) three mutually complementary protocols for methyl-branched chiral alkanols; (2) water, MAO, and IBAO as promoters to accelerate otherwise sluggish carboaluminations; (3) one-step homologation synthesis of deoxypropionates based on one-pot ZACA-Pd-catalyzed vinylation tandem process; (4) ZACA-lipase-catalyzed acetylation-transition-metal-catalyzed cross-coupling processes for preparing various virtually enantiopure chiral alcohols; (5) the chemoselective ZMA and ZACA reactions as well as alkyne elementometalation-Pd-catalyzed cross-coupling for constructing a variety of chiral compounds containing regio- and stereodefined substituted alkenes; (6) the ZACA reaction of dienes to generate chiral organocyclic compounds including those with all-carbon quaternary stereocenters. PMID- 27685326 TI - Association of MicroRNA-149 Polymorphism with Lung Cancer Risk in Chinese Non Smoking Female: A Case-Control Study. AB - INTRODUCTION: Rs2292832 is a single nucleotide polymorphism located in the precursor of mir-149 and was reported to be associated with varieties of malignancies. So far, the effect of miR-149 rs2292832 polymorphism on lung cancer risk was unclear. In addition, cooking oil fume exposure was demonstrated to be an important environmental risk factor in Chinese female. The aim of the present study was to evaluate the associations of rs2292832 polymorphism, cooking oil fume exposure and multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism with lung cancer risk in Chinese non-smoking female population. METHODS: The present study was a hospital-based case-control study conducted in Chinese non-smoking females. 555 lung cancer patients and 395 cancer free controls were interviewed to collect demographic data and exposure status of environmental risk factors, and then donate 10 ml venous blood which was used to be genotyped by Taqman allelic discrimination method. The statistical analyses were performed on SPSS 13.0 software. RESULTS: The association between miR-149 rs2292832 polymorphism and risk of lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767-1.321, P = 0.963; CC vs. TT: OR = 0.41, 95%CI = 0.532-1.329, P = 0.458; Dominant model: OR = 0.965, 95%CI = 0.745-1.251, P = 0.788; Recessive model: OR = 0.816, 95%CI = 0.528-1.259, P = 0.357, adjusted for age), non-small cell lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767-1.321, P = 0.963; CC vs. TT: OR = 0.841, 95%CI = 0.532-1.329, P = 0.458, adjusted for age), lung adenocarcinoma(TC vs. TT: OR = 0.944, 95%CI = 0.700-1.273, P = 0.707; CC vs. TT: OR = 0.801, 95%CI = 0.485-1.323, P = 0.386, adjusted for age) and squamous cell carcinoma(TC vs. TT: OR = 1.025, 95%CI = 0.641-1.638, P = 0.919; CC vs. TT: OR = 0.792, 95%CI = 0.346-1.813, P = 0.581, adjusted for age) were all not statistically significant. Result of Logistic regression showed that the multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism was not statistically significant (P = 0.063 for lung cancer and P = 0.064 for lung adenocarcinoma). CONCLUSION: MicroRNA-149 rs2292832 polymorphism may not be associated with lung cancer risk in Chinese non-smoking female. PMID- 27685329 TI - Intravascular Delivery of Biologics to the Rat Kidney. AB - The renal microvascular compartment plays an important role in the progression of kidney disease and hypertension, leading to the development of End Stage Renal Disease with high risk of death for cardiovascular events. Moreover, recent clinical studies have shown that renovascular structure and function may have a great impact on functional renal recovery after surgery. Here, we describe a protocol for the delivery of drugs into the renal artery of rats. This procedure offers significant advantages over the frequently used systemic administration as it may allow a more localized therapeutic effect. In addition, the use of rodents in pharmacodynamic analysis of preclinical studies may be cost effective, paving the way for the design of translational experiments in larger animal models. Using this technique, infusion of rat recombinant Vascular Endothelial Growth Factor (VEGF) protein in rats has induced activation of VEGF signaling as shown by increased expression of FLK1, pAKT/AKT, pERK/ERK. In summary, we established a protocol for the intrarenal delivery of drugs in rats, which is simple and highly reproducible. PMID- 27685330 TI - Associations between an Invasive Plant (Taeniatherum caput-medusae, Medusahead) and Soil Microbial Communities. AB - Understanding plant-microbe relationships can be important for developing management strategies for invasive plants, particularly when these relationships interact with underlying variables, such as habitat type and seedbank density, to mediate control efforts. In a field study located in California, USA, we investigated how soil microbial communities differ across the invasion front of Taeniatherum caput-medusae (medusahead), an annual grass that has rapidly invaded most of the western USA. Plots were installed in habitats where medusahead invasion is typically successful (open grassland) and typically not successful (oak woodland). Medusahead was seeded into plots at a range of densities (from 0 50,000 seeds/m2) to simulate different levels of invasion. We found that bacterial and fungal soil community composition were significantly different between oak woodland and open grassland habitats. Specifically, ectomycorrhizal fungi were more abundant in oak woodlands while arbuscular mycorrhizal fungi and plant pathogens were more abundant in open grasslands. We did not find a direct effect of medusahead density on soil microbial communities across the simulated invasion front two seasons after medusahead were seeded into plots. Our results suggest that future medusahead management initiatives might consider plant microbe interactions. PMID- 27685331 TI - Pain severity reduction in subjects with knee osteoarthritis decreases motor cognitive dual-task costs. AB - BACKGROUND: Pain has disruptive effects on cognitive functions leading to a decreased capability to multi task. This might be the reason why pain is a fall risk factor in dual-task situations. This study aims to relate a decrease/increase in pain severity with a decrease/increase in dual-task costs of gait variability, which is associated with fall risk, in patients with osteoarthritis prior to and 6-8weeks after total knee replacement. METHODS: We assessed the variability of minimum toe clearance in normal walking and dual-task walking in 36 patients (14 male and 22 female participants; age=mean 64.4, SD (9.2) years) with knee osteoarthritis one day before total knee replacement and again 6-8weeks after the operation. We assessed pain severity with the Brief Pain Inventory. Dual-task costs were calculated as the percentage change of gait variability from single-task walking to dual-task walking. We subtracted the post test values from the pre-test values of both outcomes to get absolute changes. We calculated the correlation using Kendall's Tau. FINDINGS: Subjects with a high difference of pain severity were more likely to have higher differences of dual task costs of gait variability (rtau=0.416, p=0.000). INTERPRETATION: Our data suggest that a reduction of pain severity goes along with a reduction in dual task costs. This indicates that pain might have substantial influence on fall risk in daily-life multi-task situations due to its detrimental effects on cognitive processes which may be adequately addressable by interventions that alleviate pain. PMID- 27685332 TI - Determinants and Time Trends for Ischaemic and Haemorrhagic Stroke in a Large Chinese Population. AB - BACKGROUND: The clinical epidemiology of stroke has been widely investigated in Caucasian populations, but the changes over time in the proportion of ischaemic to haemorrhagic strokes is less clear, especially in the Chinese population. AIMS: Our objective was to study the determinants and time trends for ischaemic and haemorrhagic stroke, in relation to age, in a large Chinese population cohort. METHODS: Using a medical insurance database in the southwest of China from 2001 to 2012, time trends in age-adjusted ischaemic and haemorrhagic stroke incidence and the contributing risk factors associated with age were investigated. RESULTS: Among 425,901 individuals without prior stroke (52.4% male, median age 54), the rate of ischaemic stroke (per 1000 patient-years) decreased between 2002-2007, then remained broadly similar between 2008-2012. The rate of haemorrhagic stroke showed a similar trend, being approximately 1.3-1.9 from 2008-2012. Compared to patients age<65, ischaemic and haemorrhagic stroke incidences (rate, 95% confidential interval, CI) were higher in the elderly population (age <65 versus age >=65: ischaemic: 3.64, 3.33-4.00, vs 14.33, 14.01 14.60; haemorrhagic: 1.09, 1.00-1.10 vs 2.52,2.40-2.70, respectively, both p<0.001). There were no significant differences in haemorrhagic stroke rates between the elderly and the very elderly population. Ischaemic and haemorrhagic stroke shared similar risk factors (age, hypertension, coronary artery disease (CAD), vascular disease, and diabetes mellitus) (all p<0.05). In subjects age<75 years, CAD (7.17, 4.14-12.37) and diabetes mellitus (3.27, 2.42-4.42) contributed most to the developing of haemorrhagic stroke (all p<0.001). Amongst the very elderly, vascular disease (2.24, 1.49-3.37) was an additional major risk factor for haemorrhagic stroke, together with CAD and diabetes mellitus (all p<0.001). CONCLUSION: In this large Chinese cohort, there was an increased risk of ischaemic stroke compared to haemorrhagic stroke with ageing. CAD, vascular disease, diabetes mellitus, and hypertension were major contributors to the development of hemorrhagic stroke in the very elderly Chinese population. PMID- 27685333 TI - Assays to Detect UV-reflecting Structures and Determine their Importance in Mate Preference using the Sailfin Molly Poecilia latipinna. AB - Many organisms use cues and signals beyond human sensitivity during social interactions. It is important to take into account how organisms perceive their worlds when trying to understand their behavior and ecology. Sensitivity to the ultraviolet spectrum (UV; 300 - 400 nm) is found across multiple genera of birds, fish, reptiles, amphibians, and even mammals. This protocol describes a technique for examining organisms for the presence of UV-reflecting structures and a method for testing whether these cues are used as social signals in the context of mate choice. A spectrophotometer is used to detect the presence of UV reflectance and variation in reflective intensity between individuals and sexes. An example of this technique is presented in which a dichotomous mate choice test exposes sexually receptive individuals to opposite sex individuals whose visual appearance can be manipulated by filters that either transmit full spectrum or block UV wavelengths. This system allowed for the determination that female, but not male, sailfin mollies (Poecilia latipinna) were using UV markings as part of their mating decisions. These types of studies serve to expand our knowledge of the range of organisms that utilize UV and provide insight into how UV plays a role in their lives. PMID- 27685334 TI - Fluorescent Orthotopic Mouse Model of Pancreatic Cancer. AB - Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors. PMID- 27685335 TI - Information-Seeking Behavior of Greek Nursing Students: A Questionnaire Study. AB - The aim of this study was to investigate factors influencing the use of electronic journals by nursing students through identification of information needs, information resources used, and barriers to seeking information. A cross sectional study was conducted using a specially designed structured questionnaire. Of 600 nursing students, 505 agreed to participate, indicating a response rate of 84.2%. Participants sought out nurses and doctors, printed materials, scholarly databases/e-journals, and seminars as information resources. Participants reported that they searched for information for themselves, parents, and inpatients. Most searched for information for diet or special nutrition needs and for specific diseases. The obstacles faced included lack of time and cost. Training in information literacy is important to enhance the skills of nursing students. PMID- 27685336 TI - Structurally Flexible and Solution Stable [Ln4TM8(OH)8(L)8(O2CR)8(MeOH)y](ClO4)4: A Playground for Magnetic Refrigeration. AB - The family of compounds of general formula [LnIII4TMII8(OH)8(L)8(O2CR)8(MeOH)y](ClO4)4 {[Gd4Zn8(OH)8(hmp)8(O2CiPr)8](ClO4)4 (1a); [Y4Zn8(OH)8(hmp)8(O2CiPr)8](ClO4)4 (1b); [Gd4Cu8(OH)8(hmp)8(O2CiPr)8](ClO4)4 (2a); [Y4Cu8(OH)8(hmp)8(O2CiPr)8](ClO4)4 (2b); [Gd4Cu8(OH)8(hep)8(O2CiPr)8](ClO4)4 (3a); [Gd4Cu8(OH)8(Hpdm)8(O2CtBu)8](ClO4)4 (4a); [Gd4Cu8(OH)8(ea)8(O2CMe)8](ClO4)4 (5a); [Gd4Ni8(OH)8(hmp)8(O2CEt)8(MeOH)6](ClO4)4 (6a); [Y4Ni8(OH)8(hmp)8(O2CEt)8(MeOH)6](ClO4)4 (6b); [Gd4Co8(OH)8(hmp)8(O2CEt)8(MeOH)6](ClO4)4 (7a); [Y4Co8(OH)8(hmp)8(O2CEt)8(MeOH)6](ClO4)4 (7b)} can be formed very simply and in high yields from the reaction of Ln(NO3)3.6H2O and TM(ClO4)2.6H2O and the appropriate ligand blend in a mixture of CH2Cl2 and MeOH in the presence of a suitable base. Remarkably, almost all the constituent parts, namely the lanthanide (or rare earth) ions LnIII (here Ln = Gd or Y), the transition metal ions TMII (here TM = Zn, Cu, Ni, Co), the bridging ligand L (Hhmp = 2 (hydroxymethyl)pyridine; Hhep = 2-(hydroxyethyl)pyridine; H2pdm = pyridine-2,6 dimethanol; Hea = 2-ethanolamine), and the carboxylates can be exchanged while maintaining the structural integrity of the molecule. NMR spectroscopy of diamagnetic complex 1b reveals the complex to be fully intact in solution with all signals from the hydroxide, ligand L, and the carboxylates equivalent on the NMR time scale, suggesting the complex possesses greater symmetry in solution than in the solid state. High resolution nano-ESI mass spectrometry on dichloromethane solutions of 2a and 2b shows both complexes are present in two charge states with little fragmentation; with the most intense peak in each spectrum corresponding to [Ln4Cu8(OH)8(hmp)8(O2CiPr)8](ClO4)22+. This family of compounds offers an excellent playground for probing how the magnetocaloric effect evolves by introducing either antiferromagnetic or ferromagnetic interactions, or magnetic anisotropy, by substituting the nonmagnetic ZnII (1a) with CuII (2a), NiII (6a) or CoII (7a), respectively. The largest magnetocaloric effect is found for the ferromagnetically coupled complex 6a, while the predominant antiferromagnetic interactions in 2a yield an inverse magnetocaloric effect; that is, the temperature increases on lowering the applied field, under the proper experimental conditions. In spite of increasing the magnetic density by adding ions that bring in antiferromagnetic interactions (2a) or magnetic anisotropy (7a), the magnetocaloric effect is overall smaller in 2a and 7a than in 1a, where only four GdIII spins per molecule contribute to the magnetocaloric properties. PMID- 27685337 TI - Effect of antiviral therapy for HCV on lipid levels. AB - BACKGROUND: HCV has complex interactions with human lipid metabolism leading to down regulation of cholesterol levels. Interferon (IFN) therapy has been shown to decrease cholesterol even further. With the availability of second-generation direct-acting antiviral agents (DAA) the effect of suppressing and eliminating HCV on lipid metabolism warrants reevaluation. METHODS: Prospective German multicentre cohort on HCV- and HIV-HCV-infected patients treated with direct antiviral agents (GECCO). Lipids were assessed at baseline, during and after therapy. Wilcoxon test corrected for multiple testing was used. RESULTS: For the analysis, 520 patients with chronic hepatitis C were available. Patients with chronic hepatitis C were treated as follows: sofosbuvir (SOF)/pegylated IFN (PEG IFN)/ribavirin (RBV; HCV=34, HIV-HCV=36), SOF/RBV (HCV=47, HIV-HCV=16), SOF/simeprevir (HCV=9, HCV-HIV=2), SOF/daclatasvir +/- RBV (HCV=27, HIV-HCV=47), SOF/ledipasvir +/- RBV (HCV=147, HCV-HIV=100) and ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- RBV (2D, HCV=2, HCV-HIV=6; 3D, HCV=39, HCV-HIV=8). On treatment there was a statistically significant increase in total cholesterol for any IFN-free DAA regimen, which was maintained after end of therapy. Changes of total cholesterol were driven by changes in low density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol remained unchanged. In contrast, total cholesterol decreased on SOF/PEG-IFN/RBV and increased after end of therapy above baseline levels. Triglycerides increased during treatment with SOF/PEG-IFN/RBV, but not on DAA-only regimens. CONCLUSIONS: Suppressing and eliminating HCV with IFN-free DAA regimens increased cholesterol levels, but had no effect on triglycerides. In contrast IFN-based therapy decreased cholesterol and increased triglycerides during treatment and led to increases in cholesterol after achieving sustained virological response. PMID- 27685340 TI - Generic Adaptive Resolution Method for Reverse Mapping of Polymers from Coarse Grained to Atomistic Descriptions. AB - In this paper, we propose a new generic approach for reverse mapping from coarse grained to atomistic scale based on the adaptive resolution scheme (AdResS). In AdResS simulation, two spatial domains, modeled at two different scales, are brought together in a concurrent simulation by defining a hybrid region where particles can switch representation from one model to another. We use AdResS as a central part of a reverse mapping algorithm from a different perspective by treating the whole simulation box as a hybrid region and changing the resolution as a function of time during the course of a molecular dynamics simulation. The proposed method depends only on a single parameter that controls the reverse mapping process and it is independent of atomistic and coarse-grained force fields. We performed a reverse mapping of three different systems, simple molecules (dodecane), polymer chains (polyethylene) and ring molecules (trimethylol melamine) with a degree of coarse-graining ranging from two to ten heavy atoms. The conformational and dynamical properties of the reconstructed systems are in excellent agreement with the reference atomistic simulation. PMID- 27685338 TI - Relative differences in resting-state brain connectivity associated with long term intensive lifestyle intervention. AB - A number of studies have reported that type 2 diabetes mellitus (T2DM) is associated with alterations in resting-state activity and connectivity in the brain. There is also evidence that interventions involving physical activity and weight loss may affect brain functional connectivity. In this study, we examined the effects of nearly 10 years of an intensive lifestyle intervention (ILI), designed to induce and sustain weight loss through lower caloric intake and increased physical activity, on resting-state networks in adults with T2DM. We performed a cross-sectional comparison of global and local characteristics from functional brain networks between individuals who had been randomly assigned to ILI or a control condition of health education and support. Upon examining brain networks from 312 participants (average age: 68.8 for ILI and 67.9 for controls), we found that ILI participants (N=160) had attenuated local efficiency at the network-level compared with controls (N=152). Although there was no group difference in the network-level global efficiency, we found that, among ILI participants, nodal global efficiency was elevated in left fusiform gyrus, right middle frontal gyrus, and pars opercularis of right inferior frontal gyrus. These effects were age-dependent, with more pronounced effects for older participants. Overall these results indicate that the individuals assigned to the ILI had brain networks with less regional and more global connectivity, particularly involving frontal lobes. Such patterns would support greater distributed information processing. Future studies are needed to determine if these differences are associated with age-related compensatory function in the ILI group or worse pathology in the control group. PMID- 27685341 TI - Investigation of Intradomain Motions of a Y-Family DNA Polymerase during Substrate Binding and Catalysis. AB - DNA polymerases catalyze DNA synthesis through a stepwise kinetic mechanism that begins with binding to DNA, followed by selection, binding, and incorporation of a nucleotide into an elongating primer. It is hypothesized that subtle active site adjustments in a polymerase to align reactive moieties limit the rate of correct nucleotide incorporation. DNA damage can impede this process for many DNA polymerases, causing replication fork stalling, genetic mutations, and potentially cell death. However, specialized Y-family DNA polymerases are structurally evolved to efficiently bypass DNA damage in vivo, albeit at the expense of replication fidelity. Dpo4, a model Y-family polymerase from Sulfolobus solfataricus, has been well-studied kinetically, structurally, and computationally, which yielded a mechanistic understanding of how the Y-family DNA polymerases achieve their unique catalytic properties. We previously employed a real-time Forster resonance energy transfer (FRET) technique to characterize the global conformational motions of Dpo4 during DNA binding as well as nucleotide binding and incorporation by monitoring changes in distance between sites on the polymerase and DNA, and even between domains of Dpo4. Here, we extend the utility of our FRET methodology to observe conformational transitions within individual domains of Dpo4 during DNA binding and nucleotide incorporation. The results of this novel, intradomain FRET approach unify findings from many studies to fully clarify the complex DNA binding mechanism of Dpo4. Furthermore, intradomain motions in the Finger domain during nucleotide binding and incorporation, for the first time, report on the rate-limiting step of a single-nucleotide addition catalyzed by Dpo4. PMID- 27685339 TI - 17beta-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects. AB - The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17beta-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17beta-estradiol (40MUg/kg, s.c) given prior to the behavioral tests. Co-administration of 17beta estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17beta-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17beta-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17beta-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17beta-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive improvement. PMID- 27685343 TI - Synthesis of Aminoindolizidines through the Chemoselective and Diastereoselective Catalytic Hydrogenation of Indolizines. AB - Indolizidines are bioactive heterocyclic compounds of great potential normally prepared following multistep routes. However, to the best of our knowledge, the synthesis of 1-aminoindolizidines has never been reported. Herein, 1 (dialkylamino)-3-substituted indolizidines have been straightforwardly synthesized using an atom-economic protocol that involves a copper-catalyzed three-component synthesis of indolizines followed by heterogeneous catalytic hydrogenation. The latter was found to be chemoselective using platinum(IV) oxide as the catalyst at 3.7 atm, providing the aminoindolizidines in modest-to-high yields (35-95%) and high diastereoselectivity (92:8 to >99:1). It has been experimentally demonstrated that the hydrogenation occurs through the intermediate 5,6,7,8-tetrahydroindolizine, which contains a pyrrole moiety. Moreover, the diastereomerically pure 1-(dibenzylamino)-3-substituted indolizidines could be further transformed into the corresponding monobenzylated or fully debenzylated aminoindolizidines by selective hydrogenolysis catalyzed by Pt/C or Pd/C, respectively, under ambient conditions. PMID- 27685342 TI - Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing. AB - Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The NexteraTM Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome. PMID- 27685344 TI - The Impact of Paravertebral Block Analgesia on Breast Cancer Survival After Surgery. AB - BACKGROUND AND OBJECTIVES: The impact of regional anesthesia on breast cancer recurrence is controversial. We tested the hypothesis that the use of paravertebral block (PVB) analgesia during breast cancer surgery prolongs the recurrence-free survival (RFS) and overall survival (OS) of women with breast cancer. METHODS: Seven hundred ninety-two women with nonmetastatic breast cancer were included in this retrospective study. Patients were divided based on the administration of PVB analgesia for mastectomy surgeries. One hundred ninety eight (25%) were given a PVB, the remainder were treated with opioid-based analgesia. Propensity score matching was developed using several variables. Univariate and multivariate analyses were used to assess the impact of PVB analgesia on RFS and OS. RESULTS: The median follow-up times for RFS and OS were 5.8 and 6 years, respectively. In the propensity score matching model, a total of 396 women were included in each group of treatment (non-PVB group, n = 198 vs PVB group, n = 198). As expected, the fentanyl consumption was significantly lower in PVB (122.8 +/- 77.85 MUg) patients than non-PVB subjects (402.23 +/- 343.8 MUg). Other variables were not statistically significant. After adjusting for several important covariates, the analysis indicated that the use of PVB is not associated with a significant change in RFS [1.60 (0.81-3.16), P = 0.172] or OS [1.28 (0.55-3.01)] survival. DISCUSSION: This retrospective study does not support the hypothesis that the use of regional analgesia is associated with longer survival after surgery for breast cancer. PMID- 27685346 TI - The Optimal Analgesic Block for Total Knee Arthroplasty. AB - Peripheral nerve block for total knee arthroplasty is ideally motor sparing while providing effective postoperative analgesia. To achieve these goals, one must understand surgical dissection techniques, distribution of nociceptive generators, sensory innervation of the knee, and nerve topography in the thigh. PMID- 27685345 TI - Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation for Postoperative Analgesia: Could Neurostimulation Replace Continuous Peripheral Nerve Blocks? PMID- 27685347 TI - A Randomized Controlled Trial of Ultrasound Versus Nerve Stimulator Guidance for Axillary Brachial Plexus Block. AB - BACKGROUND: Ultrasound-guided techniques improve outcomes in regional anesthesia when compared with traditional techniques; however, this assertion has not been studied with novices. The primary objective of this study was to compare sensory and motor block after axillary brachial plexus block when performed by novice trainees allocated to an ultrasound- or nerve-stimulator-guided group. A secondary objective was to compare the rates of skill acquisition between the 2 groups. METHODS: This study was a prospective, randomized, observer-blinded, 2 arm controlled trial. Anesthesia trainees participating in this trial were novices to axillary brachial plexus block and sonography. All trainee participants underwent a standardized training program. The primary outcome was combined sensory and motor block in the relevant territories 30 minutes after completion of block. A global rating scale was used to assess trainee block performance. RESULTS: The study was ceased after 12 trainees completed 153 blocks. There was no difference between groups in combined motor/sensory score (P = 0.28) or as a function of block number (P = 0.38). There was no difference in onset between groups (P = 0.38). In both groups, there was an increase in the global rating scale score (P < 0.0001) and reduced preblock survey and block performance times (P = 0.001) with experience. CONCLUSIONS: We were unable to demonstrate a difference in the efficacy of axillary brachial plexus block performed by novices when ultrasound guidance was compared with a nerve stimulator technique. There was evidence of similarly improved clinical performance of novices in both groups. PMID- 27685348 TI - Determining the Learning Curve for Acquiring Core Sonographic Skills for Ultrasound-Guided Axillary Brachial Plexus Block. AB - BACKGROUND AND OBJECTIVES: The objectives of this study were to determine the learning curve for capturing sonograms and identifying anatomical structures relevant to ultrasound-guided axillary brachial plexus block and to determine if massed was superior to distributed practice for this core sonographic skill. METHODS: Ten University of Melbourne, third- or fourth-year Doctor of Medicine students were randomized to massed or distributed practice. Participants performed 15 supervised learning sessions comprising scanning followed by feedback. A "sonographic proficiency score" was calculated by summing parameters in acquiring and interpreting the sonogram, and identifying relevant anatomical structures. RESULTS: Between the 1st and 10th sessions, the proficiency scores increased (P = 0.043). Except for one, all participants had relatively rapid increases in their "sonographic proficiency scores." There was no difference in proficiency scores between the 15th and 10th sessions (P > 0.05). There was no difference in scores between groups for the first session, (P = 0.40), 15th session (P = 0.10), or at any time. There was no difference in the slope of the increase in "sonographic proficiency score" over the first 10 scanning sessions between groups [massed, 1.1 (0.32); distributed, 0.90 (0.15); P = 0.22) presented as mean (SD)]. The 95% confidence interval for the difference in slopes between massed and distributed groups was -0.15 to 0.56. CONCLUSIONS: The proficiency of participants in capturing sonograms and identifying anatomical structures improved significantly over 8 to 10 learning sessions. Because of sample size issues, we cannot make a firm conclusion regarding massed versus distributed practice for this core sonographic skill. PMID- 27685349 TI - Screening and Optimization of Nerve Targets and Parameters Reveals Inhibitory Effect of Pudendal Stimulation on Rat Bladder Hypersensitivity. AB - BACKGROUND AND OBJECTIVES: Neuromodulation has been reported to reliably improve symptoms of bladder overactivity and sometimes pain. The effect of electrical stimulation of several nerve pathways demonstrated to alter cystometric responses to bladder distension was examined on nociceptive responses in models of bladder hypersensitivity. METHODS: Bladder hypersensitivity was produced by several published methods including neonatal inflammation, acute inflammation, and chronic stress. Effects of different sites of stimulation (L6 and T13 nerve roots, proximal and distal pudendal nerves [PNs]) on nociceptive reflex responses to urinary bladder distension in urethane-anesthetized female rats were assessed and a parametric analysis of parameters of stimulation was performed. RESULTS: Bilateral biphasic stimulation of the proximal PNs resulted in statistically significant inhibition of visceromotor and cardiovascular responses to bladder distension in rats made hypersensitive by neonatal bladder inflammation. We found a range of optimal stimulation frequencies (5-10 Hz) which produced robust inhibitory effects when using short pulse widths (100-240 MUs). Onset of inhibition was within minutes and persisted for several minutes after the stimulus was discontinued. Use of bilateral PN stimulation in acute inflammation and stress-induced hypersensitivity models as well as unilateral stimulation, very distal PN cutaneous branch stimulation, and stimulation of the T13 and L6 nerve roots all proved ineffective with the parameters used. CONCLUSIONS: This study suggests that inhibitory effects of bilateral PN stimulation can be evoked in a rodent hypersensitivity model at relatively low frequencies with short pulse widths. The onset of effect is rapid, which suggests the potential for treating episodic pain in painful bladder disorders. PMID- 27685350 TI - Labor Epidural Intolerance Due to a Congenitally Narrowed Spinal Canal. AB - Reports exist of severe upper back pain of unknown etiology after administration of large volumes into the epidural space. We present a case of an otherwise healthy parturient who developed severe upper back and neck pain after receiving only a small volume of epidural medication. Magnetic resonance imaging revealed a congenitally narrowed spinal canal because of short pedicle syndrome. Epidural injectate occupies and compresses a percentage of the spinal canal and its neuronal contents. This may result in pain and epidural intolerance when continued injectate reaches a critical point, a threshold that is lower with shortened pedicles or congenital spinal stenosis. We believe a similar mechanism may explain the pain that patients sometimes experience after administration of large epidural volumes. PMID- 27685351 TI - Molecular Mechanism of Facilitated Dissociation of Fis Protein from DNA. AB - Fis protein is a nucleoid-associated protein that plays many roles in transcriptional regulation and DNA site-specific recombination. In contrast to the naive expectation based on stoichiometry, recent single-molecule studies have shown that the dissociation of Fis protein from DNA is accelerated by increasing the concentration of the Fis protein. Because the detailed molecular mechanism of facilitated dissociation is still not clear, in this study, we employ computational methods to explore the binding landscapes of Fis:DNA complexes with various stoichiometries. When two Fis molecules are present, simulations uncover a ternary complex, where the originally bound Fis protein is partially dissociated from DNA. The simulations support a three-state sequential kinetic model (N ? I -> D) for facilitated dissociation, thus explaining the concentration-dependent dissociation. PMID- 27685354 TI - Transcriptional Analysis by Nascent RNA FISH of In Vivo Trophoblast Giant Cells or In Vitro Short-term Cultures of Ectoplacental Cone Explants. AB - The placenta derives from one extra-embryonic lineage, the trophectoderm. In the peri-implantation murine blastocyst, mural trophectoderm cells differentiate into primary trophoblast giant cells (TGCs) while the polar trophectoderm overlying the inner cell mass continues to proliferate later differentiating into secondary TGCs. TGCs play a key role in developing placenta and are essential for a successful pregnancy. Investigation of transcriptional regulation of specific genes during post-implantation development can give insights into TGCs development. Cells of the ectoplacental cone (EPC) from embryos at 7-7.5 days of gestation (E7-7.5), derived from the polar trophectoderm, differentiate into secondary TGCs1. TGCs can be studied in situ, on cryostat sections of embryos at E7 although the number of TGCs is very low at this stage. An alternative means of analyzing secondary TGCs is to use short-term cultures of individual EPCs from E7 embryos. We propose a technique to investigate the transcriptional status of genes of interest both in vivo and in vitro at the single-cell level using fluorescent in situ hybridization (RNA FISH) to visualize nascent transcripts. This technique provides a direct readout of gene expression and enables assessment of the chromosomal status of TGCs, which are large endoreplicating cells. Indeed, a key feature of terminal differentiation of TGCs is that they exit the cell cycle and undergo multiple rounds of endoreplication.This approach can be applied to detect expression of any gene expressed from autosomes and/or sex chromosomes and can provide important information into developmental mechanisms as well as placental diseases. PMID- 27685352 TI - Human intracranial recordings link suppressed transients rather than 'filling-in' to perceptual continuity across blinks. AB - We hardly notice our eye blinks, yet an externally generated retinal interruption of a similar duration is perceptually salient. We examined the neural correlates of this perceptual distinction using intracranially measured ECoG signals from the human visual cortex in 14 patients. In early visual areas (V1 and V2), the disappearance of the stimulus due to either invisible blinks or salient blank video frames ('gaps') led to a similar drop in activity level, followed by a positive overshoot beyond baseline, triggered by stimulus reappearance. Ascending the visual hierarchy, the reappearance-related overshoot gradually subsided for blinks but not for gaps. By contrast, the disappearance-related drop did not follow the perceptual distinction - it was actually slightly more pronounced for blinks than for gaps. These findings suggest that blinks' limited visibility compared with gaps is correlated with suppression of blink-related visual activity transients, rather than with "filling-in" of the occluded content during blinks. PMID- 27685356 TI - QuickStats: Colorectal Cancer Screening* Among Adults Aged 50-75 Years, by Race/Ethnicity(?) - National Health Interview Survey,(S) United States, 2000 2015. AB - During 2000-2015, among adults aged 50-75 years, the use of colorectal cancer tests or procedures increased for all racial/ ethnic groups included in the analysis. Colorectal screening percentages more than doubled for non-Hispanic black, Hispanic, and non-Hispanic Asian adults during that period. Despite these increases, in 2015, the prevalence of colorectal cancer screening was higher among non-Hispanic white (65.6%) adults than among non-Hispanic black (60.3%), non-Hispanic Asian (52.1%), and Hispanic (47.4%) adults. PMID- 27685355 TI - Phospholipid complexation of NMITLI118RT+: way to a prudent therapeutic approach for beneficial outcomes in ischemic stroke in rats. AB - Withania somnifera Dunal (Solanaceae) known as Ashwagandha, a popular plant of Indian origin is known to possess tremedous medicinal potential, often used as anti-inflammatory, anti-platelet, antihypertensive, hypoglycemic, hypolipidemic and adaptogenic candidate. Some of its chemotypes developed by CSIR, India includes NMITLI-101, NMITLI-118, NMITLI-128. In this study the investigators have attempted development of a phytosomal complex of NMITLI118RT + (standardized ethanolic extract of a new chemotype of W. somnifera Dunal.), its pharmaceutical characterization and evaluation of its neuro-protective potential against experimenal stroke in rats in continuation with their previous work in this area. The phytosomal complex (NIMPLC) was prepared by following a cohesive optimization design and was characterized on the basis of solubility, dissolution profile, FT IR, DSC-TGA analysis, zeta potential, physical stability, forced degradation and photolytic degradation. Results were suggestive of a pharmaceutically acceptable formulation. NIMPLC was taken up further for biological evaluation using the middle cerebral artery occlusion (MCAO) model in rats. It could be demonstrated that the beneficial effects of NMITLI118RT + could be augmented by NIMPLC in 1 h pre and 6 h post treatment as was evident from reduction in MDA levels, increment in GSH levels, reduction in neurological deficit (ND) scores and reduction in infarct size. The study could successfully demonstrate the beneficial effects of NIMPLC in brain function restoration following stroke. PMID- 27685353 TI - A non canonical subtilase attenuates the transcriptional activation of defence responses in Arabidopsis thaliana. AB - Proteases play crucial physiological functions in all organisms by controlling the lifetime of proteins. Here, we identified an atypical protease of the subtilase family [SBT5.2(b)] that attenuates the transcriptional activation of plant defence independently of its protease activity. The SBT5.2 gene produces two distinct transcripts encoding a canonical secreted subtilase [SBT5.2(a)] and an intracellular protein [SBT5.2(b)]. Concomitant to SBT5.2(a) downregulation, SBT5.2(b) expression is induced after bacterial inoculation. SBT5.2(b) localizes to endosomes where it interacts with and retains the defence-related transcription factor MYB30. Nuclear exclusion of MYB30 results in its reduced transcriptional activation and, thus, suppressed resistance. sbt5.2 mutants, with abolished SBT5.2(a) and SBT5.2(b) expression, display enhanced defence that is suppressed in a myb30 mutant background. Moreover, overexpression of SBT5.2(b), but not SBT5.2(a), in sbt5.2 plants reverts the phenotypes displayed by sbt5.2 mutants. Overall, we uncover a regulatory mode of the transcriptional activation of defence responses previously undescribed in eukaryotes. PMID- 27685357 TI - Comparison of Treatment Outcomes between Breast Conserving Surgery Followed by Radiotherapy and Mastectomy Alone in Patients with T1-2 Stage and 1-3 Axillary Lymph Nodes in the Era of Modern Adjuvant Systemic Treatments. AB - PURPOSE: The role of postmastectomy radiotherapy in the treatment of T1-2 primary tumor with 1-3 positive lymph nodes is controversial. We compared treatment outcomes between breast conserving surgery followed by radiotherapy (BCS+RT) and total mastectomy alone (TM) in the setting of modern adjuvant systemic treatments. METHODS: Patients with T1-2 primary breast cancer and 1-3 positive lymph nodes who were treated between 2001 and 2011 were divided into 2 groups based on the treatment approach: BCS+RT (n = 169) and TM (n = 117). All patients received adjuvant chemotherapy including taxanes. Adjuvant endocrine therapy was administered to patients with positive hormone receptors according to their menstrual status. RESULTS: During a median follow-up of 76.5 months, 21 patients (7.3%) experienced locoregional recurrence as the first event, including 7 patients (4.1%) in the BCS+RT group and 14 patients (12.0%) in the TM group. The 5-year cumulative incidence rate of locoregional recurrence was 2.5% for BCS+RT versus 9.5% for TM (p = 0.016). Competing risk regression analysis revealed that TM was associated with a relative risk for locoregional recurrence of 5.347 (p = 0.003). TM was also associated with a significantly lower 5-year disease-free survival rate compared with BCS+RT (hazard ratio, 2.024; 95% confidence interval, 1.090-3.759; p = 0.026). CONCLUSION: To improve treatment outcomes for TM even after modern systemic treatments, postmastectomy radiotherapy might be required for patients with T1-2 primary breast cancer and 1-3 positive lymph nodes. PMID- 27685358 TI - Remote Quantitative Sensory Testing and Neuropathic Ocular Pain. PMID- 27685359 TI - Linear and Nonlinear Viscoelastic Arterial Wall Models: Application on Animals. AB - This work deals with the viscoelasticity of the arterial wall and its influence on the pulse waves. We describe the viscoelasticity by a nonlinear Kelvin-Voigt model in which the coefficients are fitted using experimental time series of pressure and radius measured on a sheep's arterial network. We obtained a good agreement between the results of the nonlinear Kelvin-Voigt model and the experimental measurements. We found that the viscoelastic relaxation time-defined by the ratio between the viscoelastic coefficient and the Young's modulus-is nearly constant throughout the network. Therefore, as it is well known that smaller arteries are stiffer, the viscoelastic coefficient rises when approaching the peripheral sites to compensate the rise of the Young's modulus, resulting in a higher damping effect. We incorporated the fitted viscoelastic coefficients in a nonlinear 1D fluid model to compute the pulse waves in the network. The damping effect of viscoelasticity on the high-frequency waves is clear especially at the peripheral sites. PMID- 27685360 TI - Tarantula Hair Keratoconjunctivitis with Concurrent Fungal Infection in a Rat Terrier. AB - A 9 yr old rat terrier presented with corneal ulceration and conjunctivitis that developed acutely after digging among dry leaves in wooded northern Arizona. Ophthalmic examination revealed multiple linear foreign bodies throughout the adnexal tissue and cornea of the left eye. Manual removal of material was unsuccessful. The palpebral conjunctiva required excision with tenotomy scissors to remove structures and allow corneal healing. Microscopic examination revealed structures believed to be setae from a Theraphosidae tarantula. This was confirmed morphologically by an entomologist and by comparison with hairs from a captive spider of the suspected species. The excised tissue also contained fruiting bodies, hyphae, and microconidia consistent with Aspergillus spp. The captive spider hairs also cultured positive for Aspergillus, suggesting a relationship between this fungus and tarantulas in captivity and in their native habitat. This is the first report in the veterinary literature to confirm tarantula hair as the causative agent in keratoconjunctivitis and corneal ulceration, adding it to the list of differential diagnoses for ocular foreign body. This is also the first report to suggest a relationship between Aspergillus and tarantulas of the Theraphosidae family, which should be considered in the diagnostics and treatment of patients with suspected tarantula hair keratoconjunctivitis. PMID- 27685361 TI - Temporary Rectal Stenting for Management of Severe Perineal Wounds in Two Dogs. AB - Perineal wounds in dogs present a challenge due to limited local availability of skin for closure and constant exposure to fecal contaminants. This report describes temporary rectal stenting in two dogs following severe perineal wounds. Dog 1 presented with a 4 * 4 cm full-thickness perineal slough secondary to multiple rectal perforations. A 12 mm internal diameter endotracheal tube was placed per-rectum as a temporary stent to minimize fecal contamination. The stent was removed 18 days after placement, and the perineal wound had healed at 32 days post-stent placement, when a minor rectal stricture associated with mild, intermittent tenesmus was detected. Long-term outcome was deemed good. Dog 2 presented with multiple necrotic wounds with myiasis, circumferentially surrounding the anus and extending along the tail. A 14 mm internal diameter endotracheal tube was placed per-rectum. The perineal and tail wounds were managed with surgical debridement and wet-to-dry and honey dressings prior to caudectomy and negative pressure wound therapy (NPWT). Delayed secondary wound closure and stent removal were performed on day six without complication. Long term outcome was deemed excellent. Temporary rectal stenting may be a useful technique for fecal diversion to facilitate resolution of complex perineal injuries, including rectal perforation. PMID- 27685362 TI - Border Collie Collapse: Owner Survey Results and Veterinary Description of Videotaped Episodes. AB - Completed surveys were obtained from owners of 165 border collies experiencing repeated episodes of abnormal gait or collapse during strenuous exercise. Unremarkable veterinary evaluation and lack of disease progression over time made common systemic, cardiac, and neurologic causes of exercise intolerance unlikely. Survey questions addressed signalment, age of onset, description of episodes, and owner perception of factors associated with collapse. Most dogs were young adults (median 2 yr) when episodes began, and they had experienced from 2 to more than 100 episodes (median 6) prior to their owners completing the survey. Retrieving was the activity most commonly associated with episodes (112/165 dogs, 68%), followed by herding stock (39/165 dogs, 24%). Owners reported that high environmental temperatures (111/165 dogs, 67%) and excitement (67/165 dogs, 41%) increased the likelihood of their dog having an episode during strenuous activity. Veterinary evaluation of videotapes of presumed border collie collapse (BCC) episodes (40 dogs) were used to provide a description of the typical features of BCC episodes. Altered mentation, symmetrical ataxia affecting all four limbs, increased pelvic limb extensor tone and toe scuffing or knuckling, truncal swaying, and falling to the side were common features, suggesting that BCC may be an episodic diffuse central nervous system disorder. PMID- 27685363 TI - 2016 AAHA/IAAHPC End-of-Life Care Guidelines. AB - End-of-life (EOL) care and decisionmaking embody the critical final stage in a pet's life and are as important and meaningful as the sum of the clinical care provided for all prior life stages. EOL care should focus on maximizing patient comfort and minimizing suffering while providing a collaborative and supportive partnership with the caregiver client. Timely, empathetic, and nonjudgmental communication is the hallmark of effective client support. Veterinarians should not allow an EOL patient to succumb to a natural death without considering the option of euthanasia and ensuring that other measures to alleviate discomfort and distress are in place. Animal hospice care addresses the patient's unique emotional and social needs as well as the physical needs traditionally treated in clinical practice. An EOL treatment plan should consist of client education; evaluating the caregiver's needs and goals for the pet; and a collaborative, personalized, written treatment plan involving the clinical staff and client. Primary care practices should have a dedicated team to implement palliative and hospice care for EOL patients. How the healthcare team responds to a client's grief after the loss of a pet can be a key factor in the client's continued loyalty to the practice. Referral to professional grief-support counseling can be a helpful option in this regard. PMID- 27685364 TI - A "Light Meal" Three Hours Preoperatively Decreases the Incidence of Gastro Esophageal Reflux in Dogs. AB - Emerging evidence from veterinary and medical clinical research shows that reducing preoperative fasting time may reduce the incidence of gastro-esophageal reflux (GER) intraoperatively. In order to evaluate the effect of two different preoperative fasting times on the incidence of GER during general anesthesia, 120 dogs were randomly assigned to two groups: administration of canned food 3 h before premedication (group C3, n = 60) and administration of canned food 10 h before premedication (group C10, n = 60). The animals were premedicated with propionyl-promazine. Anesthesia was induced with thiopental sodium and maintained with halothane. A pH electrode was introduced into the esophagus, and the esophageal pH was constantly monitored. Esophageal pH of less than 4 or greater than 7.5 was taken as an indication of GER. Three of the 60 dogs of group C3 and 12 of the 60 dogs of group C10 experienced a GER episode, the difference being statistically significant (P = .025). Feeding the dog 3 h before anesthesia at a half daily rate reduces significantly the incidence of GER during anesthesia, compared to the administration of the same amount and type of food 10 h before anesthesia. The administration of a half daily dose of an ordinary canine diet may be useful in clinical practice. PMID- 27685365 TI - Computed Tomographic Evaluation of Presumptively Normal Canine Sternal Lymph Nodes. AB - The sternal lymph nodes receive drainage from a wide variety of structures in the thoraco-abdominal region. Evaluation of these lymph nodes is essential, especially in cancer patients. Computed tomography (CT) can detect sternal lymph nodes more accurately than radiography or ultrasonography, and the criteria of the sternal lymphadenopathy are unknown. The purpose of this retrospective study was to describe the CT characteristics of the sternal lymph nodes in dogs considered unlikely to have lymphadenopathy. The ratio of the short axis dimension of the sternal lymph nodes to the thickness of the second sternebra was also investigated. At least one sternal lymph node was identified in each of the 152 dogs included in the study. The mean long axis and short axis dimensions were 0.700 cm and 0.368 cm, respectively. The mean ratio of the sternal lymph nodes to the second sternebrae was 0.457, and the 95% prediction interval ranged from 0.317 to 0.596 (almost a fixed value independent of body weight). These findings will be useful when evaluating sternal lymphadenopathy using CT. PMID- 27685366 TI - Fatal Oleander Toxicosis in Two Miniature Horses. AB - Two young American miniature horses from the same farm were evaluated by a veterinarian due to presence of lethargy, anorexia, and cardiac arrhythmias. Both horses were treated aggressively with IV fluids and other supportive measures. The first horse died approximately 72 hr after the start of clinical signs and the second horse was humanely euthanized due to poor response to treatment. Oleander toxicosis was suspected based on the types of clinical signs present and due to several oleander plants and dried leaves present on the property. Oleander toxicosis was confirmed by the presence of oleandrin in gastrointestinal contents and digoxin in the serum of second horse. PMID- 27685367 TI - Cardiogenic Pulmonary Edema in a Dog Following Initiation of Therapy for Concurrent Hypoadrenocorticism and Hypothyroidism. AB - A 5 yr old intact female cocker spaniel dog weighing 7.8 kg was referred with anorexia, vomiting, and depression. At referral, the dog was diagnosed initially with typical hypoadrenocorticism, and 2 d later, concurrent primary hypothyroidism was detected. Hormonal replacement therapies, including fludrocortisone, prednisolone, and levothyroxine, were initiated, but a few days later the dog became abruptly tachypneic, and thoracic radiographs indicated the development of pulmonary edema. Echocardiography showed that there were abnormalities indicating impaired left ventricular function, although the heart valves were normal. Following treatment with pimobendan and furosemide, the pulmonary edema resolved. The dog had no recurrence of the clinical signs after 10 mo of follow-up, despite being off all cardiac medications; consequently, the cardiac failure was transient or reversible in this dog. The case report describes the stepwise diagnosis and successful treatment of cardiogenic pulmonary edema after initiation of hormonal replacement therapy for concurrent hypoadrenocorticism and hypothyroidism in a dog. PMID- 27685369 TI - Cross cultural adaptations and psychometric domains of Brazilian version of PROFILE PD for Parkinson's disease. AB - PURPOSE: The PROFILE PD scale was developed specifically to evaluate patients with Parkinson's disease (PD) within the context of the International Classification of Functioning, Disability and Health, directly applied to physical therapy practice. The study aimed to translate and cross-culturally adapt the PROFILE PD scale to Portuguese-Brazil, and to analyze its psychometric domains. METHODS: Fifty participants with PD participated in the study. We assessed the clarity of the Brazilian version of the scale by physiotherapists, presence of floor and ceiling effects, interrater and test-retest reliabilities, in addition to discriminant, concurrent (UPDRS) and construct validity, internal consistence, minimal detectable change (MDC), and responsiveness. RESULTS: The scale was considered highly clear for physical therapists. The interrater ICC was 0.74 and Wk was 0.89 for the total score. For test-retest reliability, the total ICC score was 0.99. The analysis of concurrent validity showed the Spearman correlation between Brazilian version of PROFILE PD and UPDRS (rho = 0.77; p < 0.001). Factor analyses demonstrated that the test comprises a single scale. Brazilian version of PROFILE PD was able to discriminate the subject with PD in mild and moderate stages, and in mild and severe stages. A high internal consistency was found (alpha = 0.99). MDC was 2.41 points and there were no floor and ceiling effects. Also, the scale was responsive to physical therapy intervention, with improvement in 8 points after two months (effect size = 0.85). CONCLUSION: The Brazilian version of PROFILE PD is an instrument reliable, valid, and responsive to physical therapy intervention, that can be used to quantify impairments and limitations in patients with PD and can provide an overall summary of the impact of disease, useful for physiotherapy practice. Implications for Rehabilitation PROFILE PD is a reliable and valid instrument to be applied in Brazilian Parkinson disease patients. This scale is design specially to be used in physical therapy practice within the contexts surrounding the International Classification of Functioning, Disability and Health. PROFILE PD was able to discriminate between patients in mild and moderate stages of disease which is difficult in clinical practice mainly because the scale used for this relies on balance and gait rather than a global profile. PMID- 27685370 TI - Nurses' perceptions of spiritual care and attitudes toward the principles of dying with dignity: A sample from Turkey. AB - Spiritual care is vital for holistic care and dying with dignity. The aim of this study was to determine nurses' perceptions of spiritual care and their attitudes toward dying with dignity. This study was conducted with 289 nurses working at a public hospital. Results showed three things. First, spiritual care perceptions and attitudes toward dying with dignity were more positive in female participants than in male participants. Second, there was a correlation between participants' education levels and their perceptions of spiritual care. Third, there was also a correlation between participants' attitudes toward dying with dignity and their perceptions of spiritual care. PMID- 27685368 TI - Oligomeric viral proteins: small in size, large in presence. AB - Viruses are obligate parasites that rely heavily on host cellular processes for replication. The small number of proteins typically encoded by a virus is faced with selection pressures that lead to the evolution of distinctive structural properties, allowing each protein to maintain its function under constraints such as small genome size, high mutation rate, and rapidly changing fitness conditions. One common strategy for this evolution is to utilize small building blocks to generate protein oligomers that assemble in multiple ways, thereby diversifying protein function and regulation. In this review, we discuss specific cases that illustrate how oligomerization is used to generate a single defined functional state, to modulate activity via different oligomeric states, or to generate multiple functional forms via different oligomeric states. PMID- 27685374 TI - Anger at claim that at risk children are being sent to A&E. AB - Children at risk of abuse are being sent to A&E departments by primary healthcare teams who do not want to compromise their relationship with the child's family, a child health lecturer has claimed. PMID- 27685373 TI - ? AB - News that diploma students lack practical skills will probably come as no surprise to clinical nurses. But Project 2000 critics need reminding that the lack of 'hands-on' expertise is nothing to do with the amount of time diploma students spend in the practice environment. Neither is it due to their supernumerary status. It is more likely that student failings in practical skills are because of inadequate practice based support and mentorship. PMID- 27685371 TI - Photoreduction of Shewanella oneidensis Extracellular Cytochromes by Organic Chromophores and Dye-Sensitized TiO2. AB - The transfer of photoenergized electrons from extracellular photosensitizers across a bacterial cell envelope to drive intracellular chemical transformations represents an attractive way to harness nature's catalytic machinery for solar assisted chemical synthesis. In Shewanella oneidensis MR-1 (MR-1), trans-outer membrane electron transfer is performed by the extracellular cytochromes MtrC and OmcA acting together with the outer-membrane-spanning porin?cytochrome complex (MtrAB). Here we demonstrate photoreduction of solutions of MtrC, OmcA, and the MtrCAB complex by soluble photosensitizers: namely, eosin Y, fluorescein, proflavine, flavin, and adenine dinucleotide, as well as by riboflavin and flavin mononucleotide, two compounds secreted by MR-1. We show photoreduction of MtrC and OmcA adsorbed on RuII -dye-sensitized TiO2 nanoparticles and that these protein-coated particles perform photocatalytic reduction of solutions of MtrC, OmcA, and MtrCAB. These findings provide a framework for informed development of strategies for using the outer-membrane-associated cytochromes of MR-1 for solar driven microbial synthesis in natural and engineered bacteria. PMID- 27685375 TI - Project 2000 nurses lack practical skills. AB - Newly qualified nurses lack practical skills and have difficulty Applying theoretical knowledge to practice, studies into the learning experiences of Project 2000 student nurses have found. PMID- 27685376 TI - ? AB - Thorpe House nursing home, Yorkshire, is prepared for water cuts, which the RCN has warned could cause problems for old and frail people. Yorkshire Water last week sought permission to cut off supplies for 24 hours at a time, on a rota basis from December. PMID- 27685372 TI - Inhibitory Effect of Multivalent Rhamnobiosides on Recombinant Horseshoe Crab Plasma Lectin Interactions with Pseudomonas aeruginosa PAO1. AB - To evaluate the molecular interaction of recombinant horseshoe crab plasma lectin (rHPL) with Pseudomonas aeruginosa PAO1, multivalent rhamnobioside derivatives were designed. Eight rhamnoclusters with three or four alpha(1-3)-rhamnobiosides attached to different central cores, such as methyl gallate, pentaerythritol, and N-Boc Tris, through either an ethylene glycol or a tetraethylene glycol linker, were assembled in two consecutive azide-alkyne cycloaddition click reactions. The synthetic method embraced the preparation of two alpha(1-3)-rhamnobiosides with different linker arms and their conjugation, in stoichiometric or substoichiometric amounts, to propargyl ether-functionalized tri- or tetravalent scaffolds. A divalent derivative and two self-assembling rhamnobiosides were also prepared. The different architectures and valences of the rhamnoclusters provided an opportunity to evaluate the impact of topology and valency on the binding properties toward rHPL. Inhibitory ELISA data showed that all covalently linked rhamnoclusters could inhibit P. aeruginosa PAO1 recognition activity of rHPL with high efficacy. Trivalent rhamnobiosides showed a stronger inhibitory effect on P. aeruginosa PAO1 binding, and the more flexible clusters on a pentaerythritol or a Tris core were superior to the less flexible methyl gallate-based clusters. Interestingly, the length of the linker arms had a very low impact on the binding ability of the rhamnoclusters. Herein, the two trivalent derivatives on an N-Boc protected Tris central core were the best inhibitors. The self-assembling amphiphilic rhamnobioside derivatives were found to display no multivalent effect. PMID- 27685377 TI - Once bitten. AB - Health visitors in Bolton have launched a campaign on the danger of leaving animals unattended in the presence of small children. PMID- 27685379 TI - Better healthy eating guidance needed for pregnant women. AB - Community nurses and midwives are failing to give pregnant women adequate healthy eating guidance, causing low weight births and potential ill health in later life, says a report published last week by the NCH Action for Children and the Maternity Alliance. PMID- 27685378 TI - Nurses demand safeguards as hospital invites private bids for all services. AB - Nurses set to work at a new Scottish hospital, which last week invited private firms to bid to provide its nursing services, have demanded their existing terms and conditions be protected. PMID- 27685380 TI - Audience shocked by video showing genital mutilation. AB - Nurses and other health professionals were stunned and angered last week by a video of a young girl undergoing genital mutilation, which was shown at a seminar jointly sponsored by the Royal College of Nursing and the National Council of Women. PMID- 27685383 TI - Labour claims NHS rationing costs nurses' jobs. AB - Nursing staff are key victims of increased health service rationing, Labour health spokesperson Harriet Harman said last week. PMID- 27685381 TI - ? AB - Put a not in it: packs for next year's No Smoking Day, being held on March 13, are now being distributed. For further information telephone 0171 413 1919. PMID- 27685385 TI - Central figure in establishment of nursing standard dies. AB - Douglas de Cent, who was the driving force behind the establishment of Nursing Standard in 1968, has died. PMID- 27685384 TI - Call to report colleagues who put patients at risk of harm. AB - Nurses must report colleagues who they think are not fit to practise if they suspect patients may be at risk, the organisation representing patients' watchdogs urged this week. PMID- 27685386 TI - Courses to help staff make the grade can be a waste of time. AB - Nurse practitioners are wasting time and resources attending training courses only to return to their old jobs and 'do nothing different', a London conference heard last week. PMID- 27685387 TI - ? AB - Nurse Janet Betts and her husband Paul Betts, whose daughter Leah died last week after collapsing into a coma after taking an Ecstasy tablet at her 18th birthday party. Mrs Betts, who regularly talks to schools about the dangers of drugs, has responded to the tragedy by stepping up her campaign. PMID- 27685388 TI - Restructure plans push staff to brink. AB - Nursing officers have been called to a meeting with managers at Renfrewshire Healthcare Trust this week to discuss the restructuring proposals that have brought staff to the brink of industrial action. PMID- 27685389 TI - Scottish summit. AB - The Royal College of Nursing, the Royal College of Midwives, the Scottish Health Visitors' Association and the Community and District Nurses' Association met Scottish health minister Lord James Douglas-Hamilton last week. They told the minister about low morale among Scottish nurses and the unions' fears of nurse shortages. PMID- 27685390 TI - Children's nurse chosen to advise Commons committee. AB - The Royal College of Nursing's adviser on children's nursing has been appointed as special adviser to the House of Commons health select committee. PMID- 27685393 TI - Fire crew charge nurse saves lives. AB - An A&E charge nurse's secondment to Greater Manchester's fire service to teach basic trauma life support to fire crews has led to lives being saved. PMID- 27685391 TI - Nurse practitioners 'should learn from mistakes in USA'. AB - Nurse practitioners in the UK should learn from the mistakes of their American counterparts, the RCN A&E Association's annual conference was told. PMID- 27685395 TI - ? AB - A shot in the arm: nurses were given the opportunity to practise cannulation at a skills workshop during the conference. PMID- 27685394 TI - Bereaved relatives grateful for A&E follow-up service. AB - Relatives find it extremely useful to be contacted after the sudden death of a loved one, the evaluation of one A&E department's follow-up service has found. PMID- 27685396 TI - A&E staff accused of treating crime victims insensitively. AB - Nurses and doctors treat victims of violence with insensitivity and fail to address their psychological and social needs, a nurse and manager in a London A&E department said last week. PMID- 27685397 TI - Joint prostheses at risk from GI surgery. AB - Some patients with joint prostheses should receive prophylactic antibiotics before gastrointestinal surgery, according to researchers. While it is usual for patients with prosthetic heart valves to receive prophylaxis, those with joint replacements have not been considered to be at risk of infection. The researchers report a woman who had had a knee replacement six years ago and an elective haemorrhoidectomy three months before the reported admission. PMID- 27685398 TI - Vitamin a dose and birth defects. AB - American researchers say they have quantified the risk of the teratogenicity of Vitamin A in the results of a study of 22,000 pregnant women carried out between 1984 and 1987. An increased proportion of babies with birth defects was found in women who had taken supplements of over 10,000iu per day. PMID- 27685399 TI - Protective clothing in epistaxis treatment. AB - There is a high incidence of blood contamination during the treatment of epistaxis, particularly if nasal packing is required. To assess the risk of blood contamination of staff during treatment and to gauge patients' opinions of the use of protective clothing, 50 consecutive patients with epistaxis were studied. Staff treating them wore gloves, mask, face visor, hat and apron. PMID- 27685400 TI - Same rights for nursing studentsThe four organisations which represent nearly all the UK's nursing students say they do not receive the same rights as other students. By issuing a joint charter, Tomorrow's Nurses and Midwives, they aim to change this. AB - Nursing students do not receive the same rights as other students, despite nurse teaching's move into higher education, the four organisations which represent almost all nursing students have claimed. PMID- 27685401 TI - Failing older people. AB - Elderly people who suffer a broken hip are often not receiving the nursing care they need or deserve, according to a major report from the Audit Commission, which monitors efficiency in the health service. PMID- 27685402 TI - More nursing input needed. AB - Do you have ideas which could help your health authority buy better services for your patients? PMID- 27685403 TI - Shift in service for mentally ill. AB - In her response to my article 'Piggy in the middle' (Viewpoint October 11), Sarah Sinnett makes some assumptions which I feel require correction(Letters October 25). PMID- 27685404 TI - Look at the positive aspects of our work. AB - I wish we could live in the ideal world, was my first thought after reading the letters (November 1) which showed obvious disillusionment, sadness, and anger. Of course we want to give holistic care and I believe we should continually strive to achieve this. PMID- 27685406 TI - Anger at blinkered comments. AB - I write to respond to Ms Helen Russell-Johnson's slight on the readers panel discussion on where adolescents should be nursed (Ill-informed and inexperienced views, Letters, October 25). PMID- 27685405 TI - National Association for Staff Support. AB - The recent flurry of features and correspondence on stress among nurses, has made me think that it is timely to remind Nursing Standard readers of the existence of the National Association for Staff Support known as NASS. PMID- 27685407 TI - Nurses are central to primary care. AB - Your story about our primary healthcare conference seems to imply that the nursing profession is being left out of the process of developing primary care services in London, 'Nurses side-stepped in capital's primary healthcare plans' (News November 8). Nothing could be further from the truth. PMID- 27685408 TI - Advertising poor hygiene in nursing. AB - Yet again, I was most disconcerted to see on television, nursing staff with the use of gloved hands, lifting the lid of a large rubbish pedalled bin, to put waste in. The programme was emphasising the need for more blood donors. PMID- 27685409 TI - Oestrogen levels could be affected. AB - As I understand it, randomised trials show that oestrogen replacement substantially or totally prevents post-menopause bone loss. Tamoxifen is an antioestrogen agent. Has the osteoporotic value been , explained to women volunteering for the four-year tamoxifen trials mentioned in Nursing Standard on October 18 (News)? PMID- 27685412 TI - Bottomley is still causing damage. AB - Poor Mrs Bottomley, shuffled away to Heritage but still managing to scratch at the health of our nation. PMID- 27685411 TI - Flaw in rules for student nurses. AB - It has often been argued that by attaining university status, nurse education may be transformed to the benefit of the profession as a whole. PMID- 27685410 TI - Over-emphasis on sex in relationships. AB - Apart from risking cancer by using the Pill, millions of women are at risk from venous thrombosis and embolism, heart disease, diabetes, gall bladder diseases, depression, hypertension, disorders in lipid levels and in the metabolism of carbohydrates. PMID- 27685414 TI - Masonry viewed as anti-Christian. AB - People have every right to be suspicious of the secrecy of Masonry. Masonry induces a very strong fraternal bond (Letters November 8). PMID- 27685413 TI - Clarification. AB - Linda Nazarko was reported as saying nursing homes could be run effectively without nurses, with nursing 'bought in' ('Policy needed on new care homes' News November 8). She has asked it to be made clear that this is a view of some social services departments, not her own. PMID- 27685415 TI - Information exchange. PMID- 27685416 TI - Downgrading. AB - Last month Workface explained chat a contract cannot be changed without the agreement of both parties ( 1 ). PMID- 27685417 TI - A century of X-rays. AB - The first cardiac catheterisation of the human heart is attributed to a German surgeon, Dr Werner Forssmann. Against the wishes of his superiors but with the help of his nurse assistant, Gerda Ditzen, Dr Forssmann catheterised himself using a uro- logic catheter via a cutdown in his arm. Having passed the catheter through a vein into the right side of his heart, he calmly walked to the X-ray department for a chest X-ray to confirm the precise position of the catheter within his heart. It is reported that he catheterised himself a total of nine times ( 1 , 2 ). PMID- 27685418 TI - Cardiac alert. AB - Cardiac Alert is a transtelephonic ECG monitoring service for general practitioners and high risk cardiac patients. Figures provided by the British I leart Foundation currently estimate that 300,000 people suffer a heart attack in the UK each year; 25 per cent of these people the within one hour. Of the 75 per cent who reach hospital alive, two-thirds go on to live for a year or more. Thus 43 per cent of all heart attack victims are dead within a year. World Health Organization figures show the mortality rate from coronary heart disease in Great Britain as one of the highest in the world. PMID- 27685419 TI - Heartlines. AB - Lady killer'Britain's number one lady killer isn't a man', reads the message on posters currently on display in 12 cities throughout the UK as part of a campaign launched recently by the British Heart Foundation to raise awareness about the fact that heart disease kills one in four women in the UK, the highest mortality rate in Western Europe. A woman from northern Britain is nearly twice as likely to the from heart disease as a woman in the south. PMID- 27685420 TI - Listings. AB - As there is such a huge demand, for the publication of free listings, readers may wish to take advantage of a new service being launched by Nursing Standard. For further details see the coupon in the appointments section or contact Kim Bawdier, telephone 0181 423 1066. PMID- 27685421 TI - Risk of lymph node metastasis and recommendations for elective nodal treatment in squamous cell carcinoma of the nasal cavity and maxillary sinus: a SEER analysis. AB - BACKGROUND: Risk of nodal involvement in patients with squamous cell carcinomas (SCC) of the nasal cavity and maxillary sinus has not been well defined, especially by risk factors beyond local T-stage. Additional criteria defining patients at highest risk, as well as specific nodal levels at highest risk, has been limited in small retrospective series. We describe a population-based assessment of specific nodal involvement in this group. MATERIAL AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2010 identified 1283 eligible patients with SCC of the nasal cavity or maxillary sinus. Neck involvement and individual nodal level involvement at presentation were assessed, and comparison made with a contemporaneous cohort of patients with a borderline clinically significant risk of nodal involvement and recurrence. RESULTS: Among 1283 patients, 182 (14.2%) had nodal involvement at presentation (4-27% by site and local extension). T-stage alone was associated with higher rates of nodal involvement in maxillary sinus SCC, while higher T-stage and size >2 cm were associated with higher rates of nodal involvement in nasal cavity SCC on multivariable analysis. Facial nodes and cervical nodes at levels 1 and 2 have the highest rates of involvement in T4a nasal cavity SCC, whereas nodal levels 1, 2, and/or 3 have the highest rates of involvement in T2 or higher maxillary sinus SCC when compared with a clinical reference standard. CONCLUSION: In this population-based study, there are high rates of initial nodal involvement when stratified by local extent determined by T-stage in nasal cavity SCC and maxillary sinus SCC, and independently by size in nasal cavity SCC. Involvement of the facial and nodal levels 1-3 varies depending on site and local extent of tumor involvement. These observations may help guide treatment decision making in the inclusion of and extent of elective nodal treatment fields. PMID- 27685422 TI - A systematic review of observational pain assessment instruments for use with nonverbal intubated critically ill adult patients in the emergency department: an assessment of their suitability and psychometric properties. AB - AIM AND OBJECTIVE: To examine the psychometric properties and suitability of the available observational pain instruments for potential use with nonverbal critically ill adult patients in the emergency department. BACKGROUND: In the emergency department, assessing pain in critically ill patients is challenging, especially those unable to communicate the presence of pain. Critically ill patients are commonly unable to verbally communicate pain due to altered oral communication (e.g. endotracheal intubation) and/or diminished consciousness (e.g. sedation, delirium), placing them at great risk of inadequate pain management. Over half of intensive care critically ill intubated patients experience moderate-to-severe pain whilst intubated and mechanically ventilated. DESIGN: Systematic review. DATA SOURCES: The CINAHL, EMBASE, MEDLINE, ProQuest databases, and the Cochrane Library and the National Institute of Clinical Excellence were also searched from their date of inception to April 2016, with no language restrictions applied. REVIEW METHOD: Studies were identified using predetermined inclusion criteria. Data were extracted and summarised and underwent evaluation using published classification of psychometric tests for consistency of interpretation. RESULTS: Twenty-six studies evaluating five observational pain assessment instruments that had been used with critically ill intubated patients were identified. All five instruments included behavioural indicators, with two including physiologic indicators. All five instruments have undergone validity and reliability testing involving nonverbal critically ill intubated patients, three were examined for feasibility, and one instrument underwent sensitivity and specificity testing. None have been tested within the emergency department with nonverbal critically ill intubated adult patients. CONCLUSION: The use of an appropriate and valid observational pain assessment instrument is fundamental to detecting and optimising pain management in nonverbal critically ill intubated patients in the emergency department. Of the observational pain assessment instruments reviewed, the Critical-Care Pain Observation Tool was identified as most appropriate for testing in a prospective trial in an emergency department setting. PMID- 27685423 TI - Secondary Combined Immunodeficiency in Pediatric Patients after the Fontan Operation: Three Case Reports. AB - The Fontan operation or total cavopulmonal connection (TCPC) is a palliative surgical correction of rare and complex inborn cardiac malformations that are characterized by univentricular circulation. Protein-losing enteropathy (PLE) develops in 4-13% of patients after the Fontan procedure. Fontan-related PLE leads to secondary combined immunodeficiency marked by hypogammaglobulinemia and predominantly CD4+ lymphocytopenia. Here, we present 3 case reports of patients with secondary immunodeficiency after the Fontan operation. The severity of hypogammaglobulinemia correlated with the nature of the infectious complications; however, clinical manifestations of T cell deficiency such as severe viral or opportunistic infections were not observed. The clinical consequences of the secondary combined immunodeficiency were modified by immunoglobulin replacement treatment and antibiotic prophylaxis. Heart transplantation led to the resolution of PLE signs and the restitution of IgG levels in 1 transplanted patient. Our experience shows that the immunological follow-up was delayed in all 3 patients. We suggest that all patients should be followed regularly by a clinical immunologist after the Fontan surgery. PMID- 27685424 TI - Barrett's Esophagus Commonly Diagnosed in Elderly Men with Limited Life Expectancy. PMID- 27685425 TI - Sport science integration: An evolutionary synthesis. AB - The aim of the paper is to point out one way of integrating the supposedly incommensurate disciplines investigated in sports science. General, common principles can be found among apparently unrelated disciplines when the focus is put on the dynamics of sports-related phenomena. Dynamical systems approaches that have recently changed research in biological and social sciences among others, offer key concepts to create a common pluricontextual language in sport science. This common language, far from being homogenising, offers key synthesis between diverse fields, respecting and enabling the theoretical and experimental pluralism. It forms a softly integrated sports science characterised by a basic dynamic explanatory backbone as well as context-dependent theoretical flexibility. After defining the dynamic integration in living systems, unable to be captured by structural static approaches, we show the commonalities between the diversity of processes existing on different levels and time scales in biological and social entities. We justify our interpretation by drawing on some recent scientific contributions that use the same general principles and concepts, and diverse methods and techniques of data analysis, to study different types of phenomena in diverse disciplines. We show how the introduction of the dynamic framework in sport science has started to blur the boundaries between physiology, biomechanics, psychology, phenomenology and sociology. The advantages and difficulties of sport science integration and its consequences in research are also discussed. PMID- 27685426 TI - Essential Oil of Thymus munbyanus subsp. coloratus from Algeria: Chemotypification and in vitro Biological Activities. AB - Thymus munbyanus subsp. coloratus (Lamiaceae) is a small shrub endemic to Algeria and Morocco where is found in lawns, rockeries and mountainous regions. From a phytochemical point of view this taxon has never been characterized. In this work we have analysed the chemical compositions of the essential oils obtained from inflorescences and vegetative parts by GC/MS. A new chemotype, i.e. borneol chemotype, was characterized for the first time in the species. Furthermore, we assessed the biological activities of essential oils, namely the antioxidant, antimicrobial and cytotoxicity on tumor cells that were evaluated by the DPPH, ABTS, and FRAP, disc diffusion, and MTT methods, respectively. Biological assays highlighted a moderate inhibitory effect on Staphylococcus aureus, Escherichia coli and Candida albicans (inhibition zone diameter in the range 9 - 10 mm), and noteworthy cytotoxicity on A375 human melanoma cells (IC50 of 46.95 MUg/ml). PMID- 27685427 TI - Amorphous protein aggregation monitored using fluorescence self-quenching. AB - Biophysical understanding of amorphous protein aggregation can significantly impact diverse area of biotechnology. Here, we report the time dependent salt induced formation of amorphous aggregation as monitored by fluorescence self quenching and compare the results with conventional methods for detecting protein aggregation [static light scattering (LS) and dynamic light scattering (DLS)]. As a model protein, we used a bovine pancreatic trypsin inhibitor (BPTI) variant extended by two glycines (C2G) at its C terminus, and three variants where three types of Solubility Controlling Peptide tags (SCP tags) made of five serines (C5S), alanines (C5A) or aspartic acids (C5D) were added to the C terminus of C2G. All variants have a native-like BPTI structure and trypsin inhibitory activity, but different solubilities controlled by the SCP tags. The BPTIs were labeled using NHS-Fluorescein (FAM) conjugated to BPTI's lysines, and we measured the changes in fluorescence intensity occurring upon the addition of NaCl. The fluorescence of all FAM-BPTIs decreased almost immediately, albeit to a different extent, upon addition of salt and became constant after 10 min for 24 h or more. On the other hand, LS and DLS signal changes were dependent on the type of tags. Namely, C2G's LS and DLS signals changed immediately, the signals of C5S and C5A tagged FAM-BPTIs increased slowly from 10 min to 24 h, and those of C5D remained constant. These observations indicated the presence of at least one intermediate step, with increased protein-protein interaction yielding a 'molecular condensation' phase. According to this model, C2G would rapidly turn from 'condensates' to aggregates, whereas C5S and C5A tagged FAM-BPTIs would do so slowly, and the soluble C5D tagged variant would remain in the molecular condensation state. PMID- 27685428 TI - Update of literature from cystic fibrosis registries 2012-2015. Part 6: Epidemiology, nutrition and complications. AB - Patient registries provide useful information to afford more knowledge on rare diseases like Cystic Fibrosis (CF). Twenty-two studies originating from national CF registries, focusing on demographics, survival, genetics, nutritional status, and non-pulmonary complications, were published between December 2011 and March 2015. The purpose of this review article is to examine these reports, aiming attention to the clinical characteristics of CF patients included in the registries, current, and estimated future epidemiological data, the role of gender gap, the increasing survival in different countries. Some studies offer insights into pubertal growth and non-pulmonary complications, such as liver disease, nephropathy, and cancer. Pediatr Pulmonol. 2017;52:390-398. (c) 2016 Wiley Periodicals, Inc. PMID- 27685429 TI - Comparing 2 National Organization-Level Workplace Health Promotion and Improvement Tools, 2013-2015. AB - Creating healthy workplaces is becoming more common. Half of employers that have more than 50 employees offer some type of workplace health promotion program. Few employers implement comprehensive evidence-based interventions that reach all employees and achieve desired health and cost outcomes. A few organization-level assessment and benchmarking tools have emerged to help employers evaluate the comprehensiveness and rigor of their health promotion offerings. Even fewer tools exist that combine assessment with technical assistance and guidance to implement evidence-based practices. Our descriptive analysis compares 2 such tools, the Centers for Disease Control and Prevention's Worksite Health ScoreCard and Prevention Partners' WorkHealthy America, and presents data from both to describe workplace health promotion practices across the United States. These tools are reaching employers of all types (N = 1,797), and many employers are using a comprehensive approach (85% of those using WorkHealthy America and 45% of those using the ScoreCard), increasing program effectiveness and impact. PMID- 27685430 TI - Association of Material Deprivation Status, Access to Health Care Services, and Lifestyle With Screening and Prevention of Disease, Montreal, Canada, 2012. AB - INTRODUCTION: The objective of this study was to provide information on the effect of disparities in material deprivation, access to health care services, and lifestyle on the likelihood of undergoing screening for disease prevention. METHODS: We used data from a probability sample (N = 10,726) of the Montreal population aged 15 years or older and assessed 6 dependent variables (screening for breast cancer, cervical cancer, colon cancer, blood glucose, and high blood pressure and receipt of the seasonal influenza vaccination), and 3 independent variables (disparities in material deprivation, access to health care services, and personal lifestyle habits). We used logistic regression to analyze data and determine associations. RESULTS: Use of preventive health services increased as material deprivation declined, access to health care improved, and lifestyle habits became healthier. The combined effect of household income, an individual measure, and the material deprivation index (consisting of quintiles representing a range from the most privileged [quintile 1: best education, employment, and income] to the most deprived [quintile 5: least education, employment, and income) an ecological measure, showed that having a Papanicolaou test was significantly associated with high annual household income (>=$40,000) even if the woman resided in a deprived neighborhood (quintiles 4 and 5 of the material deprivation index) (odds ratio [OR], 1.38; 95% confidence interval (95% [CI], 1.04-1.84), whereas odds of having a mammogram or influenza vaccination were significantly associated with living in a privileged neighborhood (quintiles 1, 2, and 3 of the material deprivation index) even among people with a low annual household income (<$40,000) (mammogram: OR, 1.54; 95% CI, 1.00-2.38; influenza vaccination: OR, 1.31; 95% CI, 1.04-1.66). CONCLUSION: In addition to influencing lifestyle habits and access to health care services, disparities in material deprivation influence whether a person uses preventive health services. Public health professionals need to establish screening outreach programs in socioeconomically disadvantaged neighborhoods to enhance public participation in disease prevention programs and reduce disparities in health. PMID- 27685431 TI - Age-Associated Perceptions of Physical Activity Facilitators and Barriers Among Women in Rural Southernmost Illinois. AB - INTRODUCTION: Women living in rural areas in the United States experience disproportionately high rates of diseases such as obesity and heart disease and are less likely than women living in urban areas to meet daily physical activity (PA) recommendations. The purpose of our research was to understand age-specific perceptions of barriers and facilitators to rural women engaging in PA and to identify strategies to promote PA among these women. METHODS: As part of a community health assessment to learn about women's health issues, 110 adult women participated in 14 focus groups. The women were divided into 4 age groups, and focus groups were held in various community settings. We used qualitative analysis methods to explore themes in the women's narratives, including themes related to PA knowledge, PA behavior, and access to PA facilities. RESULTS: Participants described multiple and often conflicting individual, social, and environmental barriers and facilitators to PA. Several barriers and facilitators were shared across age groups (eg, competing priorities and inadequate knowledge about PA's role in disease prevention and disease management). Other barriers (eg, illness and injury) and facilitators (eg, PA as a social opportunity) differed by age group. CONCLUSION: Rural women in southernmost Illinois have often contradictory barriers and facilitators to PA, and those barriers and facilitators are different at different points in a woman's life. Our findings suggest the need for multilevel, multisector approaches to promote PA. Additionally, this research supports the need for tailored PA promotion programs for rural women to address the barriers these women face across their lifespan. PMID- 27685432 TI - A Content Analysis of Vaping Advertisements on Twitter, November 2014. AB - INTRODUCTION: Vaping has increased in popularity, and the potential harms and benefits are largely unknown. Vaping-related advertising is expected to grow as the vaping industry grows; people are exposed primarily to vaping advertisements on the Internet, and Twitter is an especially popular social medium among young people. The primary objective of our study was to describe the characteristics of vaping-related advertisements on Twitter. METHODS: We collected data on 403,079 English-language tweets that appeared during November 2014 and contained vaping related keywords. Using crowdsourcing services, we identified vaping-related advertisements in a random sample of 5,000 tweets. The advertisement tweets were qualitatively coded for popular marketing tactics by our research team. We also inferred the demographic characteristics of followers of 4 Twitter handles that advertised various novel vape products. RESULTS: The random sample of 5,000 vaping-related tweets included 1,156 (23%) advertisement tweets that were further analyzed. Vape pens were advertised in nearly half of the advertisement tweets (47%), followed by e-juice (21%), which commonly mentioned flavors (42%). Coupons or price discounts were frequently observed (32%); only 3% of tweets mentioned vaping as a way to quit smoking or as an alternative to smoking. One handle had a disproportionately high percentage of racial/ethnic minority followers. CONCLUSION: Vaping poses a threat to smoking prevention progress, and it is important for those in tobacco control to understand and counter the tactics used by vaping companies to entice their consumers, especially on social media where young people can easily view the content. PMID- 27685433 TI - Deepening Insights of Charge Transfer and Photophysics in a Novel Donor-Acceptor Cocrystal for Waveguide Couplers and Photonic Logic Computation. PMID- 27685434 TI - Highly Anisotropic, Highly Transparent Wood Composites. PMID- 27685435 TI - Cognitive dysfunction in major depression and bipolar disorder: Assessment and treatment options. AB - Cognitive dysfunction is a recognized feature of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). Cognitive impairment is associated with poor overall functional outcome and is therefore an important feature of illness to optimize for patients' occupational and academic outcomes. While generally people with BD appear to have a greater degree of cognitive impairment than those with MDD, direct comparisons of both patient groups within a single study are lacking. There are a number of methods for the assessment of cognitive function, but few are currently used in clinical practice. Current symptoms, past course of illness, clinical features, such as the presence of psychosis and comorbid conditions, may all influence cognitive function in mood disorders. Despite the general lack of assessment of cognitive function in clinical practice, clinicians are increasingly targeting cognitive symptoms as part of comprehensive treatment strategies. Novel pharmacological agents may improve cognitive function, but most studies of standard mood stabilizers, such as lithium and the anticonvulsants, have focused on whether or not the medications impair cognition. Non-pharmacological strategies, such as cognitive remediation and exercise, are increasingly studied in patients with mood disorders. Despite the growing interest in strategies to manage cognitive function, there is a paucity of high-quality trials examining either pharmacological or non-pharmacological modes of intervention. PMID- 27685436 TI - Reply. PMID- 27685438 TI - Atrioesophageal Fistula after Minimally Invasive Video-Assisted Epicardial Ablation for Lone Atrial Fibrillation. AB - Minimally invasive video-assisted epicardial beating heart ablation for lone atrial fibrillation claims to be safe and effective. We, however, report on three patients with an atrioesophageal fistula after this procedure. The exact pathogenesis of this complication is unknown. All patients presented around 6 weeks after surgery with either fever or neurological deficits. Diagnosis can be made by computed tomography scan. We advocate an aggressive surgical approach with closure of the atrial defect on cardiopulmonary bypass and closure and reinforcement of the esophagus with an intercostal muscle flap in a single-stage surgery. Some caution as to the low-risk character of this procedure seems to be realistic. PMID- 27685437 TI - Neuropsychology in India. AB - OBJECTIVE: This is an invited paper for a special issue with the objective to provide information on neuropsychology in India. METHOD: Information was gathered from a literature search and personal communication with professionals working in the field of neuropsychology. RESULTS: Neuropsychology as a specialization started in India approximately 40 years ago. The early years witnessed the use of Western tools for assessing patients with organic brain damage. Subsequent years saw the development of indigenous tools for use with the vast majority of the Indian population and also a few Western tests adapted to suit the needs of the unique Indian clientele. The starting of the Neuropsychology unit at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bangalore in 1975 resulted in changing of the course of training and practice of Neuropsychology. The field of assessments has witnessed indigenous tests being developed, while rehabilitation programs have brought about a decline in cognitive deficits in several clinical conditions. Currently, work within the field of neuropsychology has focused on child, geriatric, acquired brain injury, and forensic populations with a development of unique rehabilitations to suit needs of several clinical conditions. However, there are very few neuropsychologists in the country, and only one nodal training center, which limits the availability of training to the large population of the country. CONCLUSION: Despite the shortcomings, the field of neuropsychology has received much attention in the recent years with the number of referrals and professionals increasing. PMID- 27685439 TI - First Hands-On Experience with the Application of a Newly Designed Double Branched Thoracic Catheter for Thoracic Interventions. AB - Background We investigated the technical handling of a y-shaped double-branched thoracic catheter with the aim of combining the effect of two separate catheters and the ease of use of a single one. Methods A total of 20 catheters were placed consecutively in 20 patients. Results In all patients, it was technically simple to position the catheter, whether in open or video-assisted surgery. The handling during removal corresponded to that of a single drain. Conclusion This type of drain appears to hold a lot of potential compared with the use of a single drain. Further studies with defined and larger patient populations should be performed. PMID- 27685440 TI - Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units. AB - The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar polyaromatic units, which are two corannulene moieties and a racemic hexahelicene linking them. The compound described in this work is a good host for fullerenes. Several common organic reactions, such as free-radical reactions, C-C coupling or click chemistry, are employed demonstrating the versatility of functionalization that this compound can accept. All of these reactions work for planar aromatic molecules. With subtle modifications, it is possible to achieve similar results for nonplanar polyaromatic compounds. PMID- 27685441 TI - A naturally-occurring 'cold earth' spot in Northern China. AB - Permafrost is determined to a large extent by the Earth's surface temperature, therefore it distributes mainly in high altitude and latitude regions. However, stable, warm (about -1 degrees C) permafrost occurs within a scree slope in northern China that is more than 600 km south of the southernmost limit of latitudinal permafrost on the Eurasian Continent. It is at an elevation of only 900 m above sea level (ASL). The area has a mean annual air temperature (MAAT) of 6 to 8 degrees C. Thermal processes of the scree slope, investigated through field monitoring and numerical simulation, showed that the permafrost is caused by winter air convection within the porous rock deposits and is stable as air convection does not occur in summer time. The deposit is covered by a 30-cm-thick peaty soil layer dated (carbon C-14) to between 1,000 to 1,600 years ago. The layer also contributes to the permafrost's existence due to the peat's thermal conductivity offset when frozen and thawed. The existence of permafrost under such warm climatic conditions confirms the effectiveness of using crushed rock layer as basement or slope cover to protect the warm permafrost subgrade of the recently-constructed Qinghai-Tibet Railway (QTR), even under the predicted climate warming conditions. PMID- 27685442 TI - Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study. AB - BACKGROUND: Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. METHODS: We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. RESULTS: We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-kappaB and IL6. CONCLUSIONS: Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker. PMID- 27685446 TI - Older patients with early-stage diffuse large B-cell lymphoma: the role of consolidation radiotherapy after chemoimmunotherapy. AB - The purpose of this study was to examine the association between RT and overall survival for older patients (>60 years) with early-stage diffuse large B-cell lymphoma (DLBCL) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998 to 2012, 2207 patients were over the age of 60 years, received chemoimmunotherapy with or without RT and were included in this study. Use of consolidation RT was associated with lower clinical stage, head/neck involved site, lack of 'B' symptoms, lower co-morbidity score, and higher socioeconomic status (all p < .05). Examining 1721 patients for survival outcomes (1998-2008), the 5-year overall survival for patients receiving RT was 80.1% versus 69.8% for those not receiving RT (p < .01). After PS-matching for co variates, RT use remained associated with improved overall survival (HR = 0.63, 95% CI, 0.51-0.79, p < .01). Over the study period, RT utilization decreased from 38.5% to 28.8%. Consolidation RT was associated with improved OS for older patients with early-stage DLBCL receiving chemoimmunotherapy. PMID- 27685443 TI - Axillary lymph node micrometastases decrease triple-negative early breast cancer survival. AB - BACKGROUND: Triple-negative breast cancers (TNBCs) are the most deadly form of breast cancer (BC) subtypes. Axillary lymph node involvement (ALNI) has been described to be prognostic in BC taken as a whole, but its prognostic value in each subtype is unclear. We explored the prognostic impact of ALNI and especially of small size axillary metastases in early TNBCs. METHODS: We analysed in this multicentre study all patients treated for early TNBC in 12 French cancer centres. We explored the correlation between clinicopathological data and ALNI, with a specific focus on the dichotomisation between macrometastases and occult metastases, which is defined as the presence of isolated tumour cells or micrometastases. The prognostic value of ALNI both in terms of disease-free survival (DFS) and overall survival (OS) was also explored. RESULTS: We included 1237 TNBC patients. Five-year DFS and OS were 83.7% and 88.5%, respectively. The identified independent prognostic features for DFS were tumour size >20 mm (hazard ratio (HR)=1.86; 95% CI: 1.11-3.10, P=0.018), lymphovascular invasion (HR=1.69; 95% CI: 1.21-2.34, P=0.002) and ALNI both in case of macrometastases (HR=1.97; 95% CI: 1.38-2.81, P<0.0001) and occult metastases (HR=1.72; 95% CI: 1.1-2.71, P=0.019). DFS and OS were similar between tumours with occult metastases and macrometastases. Tumours presenting at least two pejorative features (out of ALNI, lymphovascular invasion and large tumour size) displayed a significantly poorer DFS in both the training set and validation set, independently of chemotherapy administration. Tumours with no more than one of the above-cited pejorative features had a 5-year OS of ?90% vs 70% for other cases (P<0.0001). CONCLUSIONS: Axillary lymph node involvement is a key prognostic feature for early TNBC when isolated tumour cells were identified in lymph nodes. This impact is independent of chemotherapy use. PMID- 27685444 TI - The complexity of integrins in cancer and new scopes for therapeutic targeting. AB - Cancer is a complex disease and progresses within a dynamically evolving extracellular matrix that controls virtually every aspect of the tumour and tumour-associated cells. Interactions with the extracellular microenvironment are predominately mediated by a family of cell-surface transmembrane receptors called integrins. Integrin-matrix engagement leads to the formation of adhesion plaques, consisting of signalling and adaptor proteins, at the plasma membrane that link the extracellular matrix to the regulation of the cell cytoskeleton. In this review, we will highlight exciting data that identify new roles for integrins and integrin-dependent signalling in cancer away from the plasma membrane, discuss the implications of integrin-dependent regulation of Met and ErbB2 growth factor receptors and highlight the role of specific integrins in different stages of cancer development including maintenance of cancer stem cells. PMID- 27685447 TI - Changes in the Plasticity of HIV-1 Nef RNA during the Evolution of the North American Epidemic. AB - Because of a high mutation rate, HIV exists as a viral swarm of many sequence variants evolving under various selective pressures from the human immune system. Although the Nef gene codes for the most immunogenic of HIV accessory proteins, which alone makes it of great interest to HIV research, it also encodes an RNA structure, whose contribution to HIV virulence has been largely unexplored. Nef RNA helps HIV escape RNA interference (RNAi) through nucleotide changes and alternative folding. This study examines Historic and Modern Datasets of patient HIV-1 Nef sequences during the evolution of the North American epidemic for local changes in RNA plasticity. By definition, RNA plasticity refers to an RNA molecule's ability to take alternative folds (i.e., alternative conformations). Our most important finding is that an evolutionarily conserved region of the HIV 1 Nef gene, which we denote by R2, recently underwent a statistically significant increase in its RNA plasticity. Thus, our results indicate that Modern Nef R2 typically accommodates an alternative fold more readily than Historic Nef R2. Moreover, the increase in RNA plasticity resides mostly in synonymous nucleotide changes, which cannot be a response to selective pressures on the Nef protein. R2 may therefore be of interest in the development of antiviral RNAi therapies. PMID- 27685445 TI - FOXO3a and the MAPK p38 are activated by cetuximab to induce cell death and inhibit cell proliferation and their expression predicts cetuximab efficacy in colorectal cancer. AB - BACKGROUND: Cetuximab, a monoclonal antibody against EGFR used for the treatment of colorectal cancer (CRC), is ineffective in many patients. The aim of this study was to identify the signalling pathways activated by cetuximab in CRC cells and define new biomarker of response. METHODS: We used in vitro, in vivo models and clinical CRC samples to assess the role of p38 and FOXO3a in cetuximab mechanism of action. RESULTS: We show that cetuximab activates the MAPK p38. Specifically, p38 inhibition reduced cetuximab efficacy on cell growth and cell death. At the molecular level, cetuximab activates the transcription factor FOXO3a and promotes its nuclear translocation via p38-mediated phosphorylation, leading to the upregulation of its target genes p27 and BIM and the subsequent induction of apoptosis and inhibition of cell proliferation. Finally, we found that high FOXO3a and p38 expression levels are associated with better response rate and improved outcome in cetuximab-treated patients with CRC harbouring WT KRAS. CONCLUSIONS: We identify FOXO3a as a key mediator of cetuximab mechanism of action in CRC cells and define p38 as its activator in this context. Moreover, high FOXO3a and p38 expression could predict the response to cetuximab in patients with CRC harbouring WT KRAS. PMID- 27685449 TI - Do chromosome changes in blood cells implicate formaldehyde as a leukemogen? AB - Formaldehyde (FA) is a mutagenic chemical - a property mitigated in vivo by rapid detoxification and limited tissue distribution following inhalation of the free agent. Endogenously produced FA is necessary for life and required for one-carbon transfer reactions; however, FA derived from external sources (exogenous FA), which may be in the form of methanol, may increase in vivo concentrations above naturally occurring physiological levels. Both endogenous and exogenous FA produce DNA monoadducts, DNA-DNA and DNA-protein cross-links (DDX and DPX) but, when exposed to exogenously-derived free FA, DNA monoadducts, DDX, and DPX are only produced at initial sites of contact. In contrast, methanol may systemically induce DNA adducts distally. FA also induces oxidative stress/lipid peroxidation with some individuals suggesting the resulting reactive aldehydes may have the potential to induce distal site DNA damage with the resulting reactive aldehydes having the potential to induce distal site DNA damage. Chromosome changes in the form of aberrations or micronuclei in blood cells have been studied in FA-exposed animals and humans, with most of the former being negative. Human occupational studies have given mixed results for such changes in peripheral blood lymphocytes (PBLs) which circulate widely but do not reflect recent bone marrow (BM) events. Recent studies reporting changes in human BM or hematopoietic precursor cells (HPCs) either have had confounding exposures or could not distinguish in vivo from in vitro occurrences. The reported genetic changes in circulating blood cells do not provide convincing support for FA's classification as a human leukemogen. PMID- 27685450 TI - Abdominal Cystic-Like Lesion as a Rare Complication of Neglected Infectious Disease. PMID- 27685451 TI - Providing support to nursing students in the clinical environment: a nursing standard requirement. AB - AIM: This discussion paper poses the question 'What enables or deters Registered Nurses to take up their professional responsibility to support undergraduate nursing students through the provision of clinical education?'. BACKGROUND: Embedded within many nursing standards are expectations that Registered Nurses provide support and professional development to undergraduate nursing students undertaking clinical placements. Expectations within nursing standards that Registered Nurses provide support and professional development to nursing students are important because nursing students depend on Registered Nurses to help them to become competent practitioners. RESULTS: Contributing factors that enable and deter Registered Nurses from fulfilling this expectation to support nursing students in their clinical learning include; workloads, preparedness for the teaching role, confidence in teaching and awareness of the competency requirement to support students. CONCLUSION: Factors exist which can enable or deter Registered Nurses from carrying out the licence requirement to provide clinical education and support to nursing students. PMID- 27685448 TI - Health-Related Quality of Life and Survival of Cholangiocarcinoma Patients in Northeastern Region of Thailand. AB - In northeast Thailand, cholangiocarcinoma (CCA) is a major cause of mortality. Patients with CCA have a poor prognosis and short-term survival. The purpose of this study was to investigate the association between health-related quality of life (HRQOL) and survival time, and to explore whether change in HRQOL score is related to survival among CCA patients. The study was performed between February 2011 and January 2012, and included 171 patients with newly diagnosed CCA from 5 tertiary hospitals in four provinces of northeast Thailand. The HRQOL was measured at baseline, 1 month, and 2 months after diagnosis by the FACT-Hep questionnaire (Thai version 4). The outcome was survival time from diagnosis. Cox's proportional hazard model was used to evaluate the association between HRQOL and survival time. A higher overall score on HRQOL was associated with a significantly better survival (HR per 5 units increase in HRQOL was 0.92, 95% CI: 0.88-0.96). Two of the separate domains contributing to the overall HRQOL functional well-being and hepatobiliary cancer subscale-were found to have independent effects on survival, even after adjustment for potential confounding variables, and the other domains of HRQOL. CCA patient whose HRQOL scores had improved (>=9 units) at the 1st month of follow up had a reduced probability of dying from the disease (HR: 0.56, 0.32-0.95) after adjustment for the same confounding factors. A positive association between HRQOL at diagnosis and survival time was found. An improvement in HRQOL score in the first months after diagnosis further increases survival. PMID- 27685453 TI - Dimensionality and Valency Dependent Quantum Growth of Metallic Nanostructures: A Unified Perspective. AB - Quantum growth refers to the phenomena in which the quantum mechanically confined motion of electrons in metallic wires, islands, and films determines their overall structural stability as well as their physical and chemical properties. Yet to date, there has been a lack of a unified understanding of quantum growth with respect to the dimensionality of the nanostructures as well as the valency of the constituent atoms. Based on a first-principles approach, we investigate the stability of nanowires, nanoislands, and ultrathin films of prototypical metal elements. We reveal that the Friedel oscillations generated at the edges (or surfaces) of the nanostructures cause corresponding oscillatory behaviors in their stability, leading to the existence of highly preferred lengths (or thicknesses). Such magic lengths of the nanowires are further found to depend on both the number of valence electrons and the radial size, with the oscillation period monotonously increasing for alkali and group IB metals, and monotonously decreasing for transition and group IIIA-VA metals. When the radial size of the nanowires increases to reach ~10 A, the systems equivalently become nanosize islands, and the oscillation period saturates to that of the corresponding ultrathin films. These findings offer a generic perspective of quantum growth of different classes of metallic nanostructures. PMID- 27685452 TI - The Stress-Strain Data of the Hip Capsule Ligaments Are Gender and Side Independent Suggesting a Smaller Contribution to Passive Stiffness. AB - BACKGROUND: The ligaments in coherence with the capsule of the hip joint are known to contribute to hip stability. Nevertheless, the contribution of the mechanical properties of the ligaments and gender- or side-specific differences are still not completely clear. To date, comparisons of the hip capsule ligaments to other tissues stabilizing the pelvis and hip joint, e.g. the iliotibial tract, were not performed. MATERIALS & METHODS: Hip capsule ligaments were obtained from 17 human cadavers (9 females, 7 males, 13 left and 8 right sides, mean age 83.65 +/- 10.54 years). 18 iliofemoral, 9 ischiofemoral and 17 pubofemoral ligaments were prepared. Uniaxial stress-strain properties were obtained from the load deformation curves before the secant elastic modulus was computed. Strain, elastic modulus and cross sections were compared. RESULTS: Strain and elastic modulus revealed no significant differences between the iliofemoral (strain 129.8 +/- 11.1%, elastic modulus 48.8 +/- 21.4 N/mm2), ischiofemoral (strain 128.7 +/- 13.7%, elastic modulus 37.5 +/- 20.4 N/mm2) and pubofemoral (strain 133.2 +/- 23.7%, elastic modulus 49.0 +/- 32.1 N/mm2) ligaments. The iliofemoral ligament (53.5 +/- 15.1 mm2) yielded a significantly higher cross section compared to the ischiofemoral (19.2 +/- 13.2 mm2) and pubofemoral (15.2 +/- 7.2 mm2) ligament. No significant gender- or side-specific differences were determined. A comparison to the published data on the iliotibial tract revealed lower elasticity and less variation in the ligaments of the hip joint. CONCLUSION: Comparison of the mechanical data of the hip joint ligaments indicates that their role may likely exceed a function as a mechanical stabilizer. Uniaxial testing of interwoven collagen fibers might lead to a misinterpretation of the mechanical properties of the hip capsule ligaments in the given setup, concealing its uniaxial properties. This underlines the need for a polyaxial test setup using fresh and non-embalmed tissues. PMID- 27685454 TI - Learning globally to enhance local practice: an international programme in primary care & family health. AB - PURPOSE: In a global context of growing health inequities, international learning experiences have become a popular strategy for equipping health professionals with skills, knowledge, and competencies required to work with the populations they serve. This study sought to analyse the Chilean Interprofessional Programme in Primary Health Care (CIPPHC), a 5 week international learning experience funded by the Ministry of Health in Chile targeted at Chilean primary care providers and delivered in Toronto by the Department of Family and Community Medicine at the University of Toronto. METHOD: The study focused on three cohorts of students (2010-2012). Anonymous programme evaluations were analysed and semi structured interviews conducted with programme alumni. Simple descriptive statistics were gathered from the evaluations and the interviews were analysed via thematic content analysis. RESULTS: The majority of participants reported high levels of satisfaction with the training programme, knowledge gain, particularly in the areas of the Canadian model of primary care, and found the materials delivered to be applicable to their local context. CONCLUSIONS: The CIPPHC has proven to be a successful educational initiative and provides valuable lessons for other academic centres in developing international interprofessional training programmes for primary care health care providers. PMID- 27685455 TI - Clinical Impact and Cost-Effectiveness of an Education Program for PD Patients: A Randomized Controlled Trial. AB - BACKGROUND: Parkinson's disease (PD) is characterized by its impact on quality of life, constituting a substantial economic burden on society. Education programs implicating patients more in the management of their illness and complementing medical treatment may be a beneficial adjunct in PD. This study assessed the impact of an education program on quality of life and its cost-effectiveness in PD patients. METHODS: This single-center, prospective, randomized study assessed an education program consisting of individual and group sessions over a 12-month period. A total of 120 PD patients were assigned to either the Treated by Behavioral Intervention group (TTBI) or the no TTBI group. The primary outcome criterion was quality of life assessed using PDQ39. The Unified Parkinson's Disease Rating Scale (UPDRS) and psychological status were collected. An economic evaluation was performed, including calculations of incremental cost effectiveness ratios (ICERs). RESULTS: After 12 months of follow-up, changes recorded in the PDQ39 between the groups were not significantly different but better changes were observed in each dimension in the TTBI group compared to the no TTBI group. UPDRS I, II and total score were significantly improved in TTBI group compared to the no TTBI group. Mean annual costs did not differ significantly between the two groups. CONCLUSION: This study suggested that the education program positively impacts the perceived health of PD patients without increasing medical costs. PMID- 27685458 TI - An update on the pharmaceutical management of thrombosis. AB - INTRODUCTION: Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs. Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes. ASO interfering with Factor XI hepatic synthesis were effective and safe for thromboprophylaxis in elective knee arthroplasty. Expert opinion: DOACs have overcome some limitations of anticoagulants such as VKA, but are still associated with a risk of bleeding and they lack both standardized and widely available tests measuring their anticoagulant effect and a reversal agent, except for idarucizumab, specific for dabigatran, in case of major or life threatening bleeding or emergency surgery. Agents targeting Factor XI and possibly Factor XII may be ideal anticoagulants, as they can prevent thrombosis with low bleeding risk. PMID- 27685456 TI - Positive affect and its association with viral control among women with HIV infection. AB - OBJECTIVE: We assessed the relationship between positive affect and viral suppression among women with HIV infection. METHOD: Three waves of 6-month data were analyzed from 995 women on HIV antiretroviral therapy participating in the Women's Interagency HIV Study (10/11-3/13). The predictor variable was self reported positive affect over 2 waves of data collection, and the outcome was suppressed viral load, defined as plasma HIV-1 RNA <200 copies/mL, measured at a third wave. RESULTS: Women with higher positive affect (36%) were more likely to have viral suppression at a subsequent wave (OR 1.92, 95% CI [1.34, 2.74]). Adjusting for covariates and their interactions, including negative affect, Wave 1 viral suppression, adherence, study site, recruitment cohort, substance use, heavy drinking, relationship status, interpersonal difficulties, and demographics, a statistically significant interaction was detected between negative affect, positive affect and viral suppression, t(965) = -2.7, p = .008. The association of positive affect and viral suppression differed at negative affect quartile values. For those reporting no negative affect, the AOR for positive affect and viral suppression was 2.41 (95% CI [1.35, 4.31]); at a negative affect score of 2, the AOR was 1.44 (95% CI [0.87, 2.36]); and at a score of 5.5, the AOR was 0.58 (95% CI [0.24, 1.42]). CONCLUSION: Our central finding related to the interaction effect, that positive affect is associated with viral control under conditions of lower negative affect, is consistent with previous theory and research with other health outcomes, and can help guide efforts to further delineate mechanisms linking affect and health. (PsycINFO Database Record PMID- 27685459 TI - NMR Scalar Couplings across Intermolecular Hydrogen Bonds between Zinc-Finger Histidine Side Chains and DNA Phosphate Groups. AB - NMR scalar couplings across hydrogen bonds represent direct evidence for the partial covalent nature of hydrogen bonds and provide structural and dynamic information on hydrogen bonding. In this article, we report heteronuclear 15N-31P and 1H-31P scalar couplings across the intermolecular hydrogen bonds between protein histidine (His) imidazole and DNA phosphate groups. These hydrogen-bond scalar couplings were observed for the Egr-1 zinc-finger-DNA complex. Although His side-chain NH protons are typically undetectable in heteronuclear 1H-15N correlation spectra due to rapid hydrogen exchange, this complex exhibited two His side-chain NH signals around 1H 14.3 ppm and 15N 178 ppm at 35 degrees C. Through various heteronuclear multidimensional NMR experiments, these signals were assigned to two zinc-coordinating His side chains in contact with DNA phosphate groups. The data show that the Ndelta1 atoms of these His side chains are protonated and exhibit the 1H-15N cross-peaks. Using heteronuclear 1H, 15N, and 31P NMR experiments, we observed the hydrogen-bond scalar couplings between the His 15Ndelta1/1Hdelta1 and DNA phosphate 31P nuclei. These results demonstrate the direct involvement of the zinc-coordinating His side chains in the recognition of DNA by the Cys2His2-class zinc fingers in solution. PMID- 27685457 TI - Colorimetric Detection of Bacteria Using Litmus Test. AB - There are increasing demands for simple but still effective methods that can be used to detect specific pathogens for point-of-care or field applications. Such methods need to be user-friendly and produce reliable results that can be easily interpreted by both specialists and non-professionals. The litmus test for pH is simple, quick, and effective as it reports the pH of a test sample via a simple color change. We have developed an approach to take advantage of the litmus test for bacterial detection. The method exploits a bacterium-specific RNA-cleaving DNAzyme to achieve two functions: recognizing a bacterium of interest and providing a mechanism to control the activity of urease. Through the use of magnetic beads immobilized with a DNAzyme-urease conjugate, the presence of bacteria in a test sample is relayed to the release of urease from beads to solution. The released urease is transferred to a test solution to hydrolyze urea into ammonia, resulting in an increase of pH that can be visualized using the classic litmus test. PMID- 27685461 TI - Controlled Synthesis and Fluorescence Tracking of Highly Uniform Poly(N isopropylacrylamide) Microgels. AB - Stimuli-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgels have various prospective practical applications and uses in fundamental research. In this work, we use single particle tracking of fluorescently labeled PNIPAM microgels as a showcase for tuning microgel size by a rapid non-stirred precipitation polymerization procedure. This approach is well suited for prototyping new reaction compositions and conditions or for applications that do not require large amounts of product. Microgel synthesis, particle size and structure determination by dynamic and static light scattering are detailed in the protocol. It is shown that the addition of functional comonomers can have a large influence on the particle nucleation and structure. Single particle tracking by wide-field fluorescence microscopy allows for an investigation of the diffusion of labeled tracer microgels in a concentrated matrix of non-labeled microgels, a system not easily investigated by other methods such as dynamic light scattering. PMID- 27685460 TI - A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune Modulatory Effects of Liposomes and Virosomes. AB - The respiratory tract with its ease of access, vast surface area and dense network of antigen-presenting cells (APCs) represents an ideal target for immune modulation. Bio-mimetic nanocarriers such as virosomes may provide immunomodulatory properties to treat diseases such as allergic asthma. In our study we employed a triple co-culture model of epithelial cells, macrophages and dendritic cells to simulate the human airway barrier. The epithelial cell line 16HBE was grown on inserts and supplemented with human blood monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) for exposure to influenza virosomes and liposomes. Additionally, primary human nasal epithelial cells (PHNEC) and EpCAM+ epithelial progenitor cell mono-cultures were utilized to simulate epithelium from large and smaller airways, respectively. To assess particle uptake and phenotype change, cell cultures were analyzed by flow cytometry and pro-inflammatory cytokine concentrations were measured by ELISA. All cell types internalized virosomes more efficiently than liposomes in both mono- and co-cultures. APCs like MDMs and MDDCs showed the highest uptake capacity. Virosome and liposome treatment caused a moderate degree of activation in MDDCs from mono-cultures and induced an increased cytokine production in co cultures. In epithelial cells, virosome uptake was increased compared to liposomes in both mono- and co-cultures with EpCAM+ epithelial progenitor cells showing highest uptake capacity. In conclusion, all cell types successfully internalized both nanocarriers with virosomes being taken up by a higher proportion of cells and at a higher rate inducing limited activation of MDDCs. Thus virosomes may represent ideal carrier antigen systems to modulate mucosal immune responses in the respiratory tract without causing excessive inflammatory changes. PMID- 27685464 TI - Digit ratio (2D:4D) and handgrip strength in a Chinese population of Han ethnicity. AB - BACKGROUND: In humans, the relative lengths of the index finger to the ring finger (2D:4D) is a sexually dimorphic trait which correlated with prenatal sex steroids and has been increasingly used as a promising tool to evaluate the impact of prenatal hormone exposure in some traits, such as physical performance. Handgrip strength (HGS) is one potent index of physical ability and its relationship with 2D:4D ratio has been discussed in several ethnic groups. AIMS: To investigate whether there is a correlation between 2D:4D ratio and HGS in Chinese college students of Ningxia Han ethnicity. METHODS: 608 students (211 males and 397 females) of Han ethnicity were recruited from Ningxia medical university. Photocopies and HGS of both hands were collected at Yinchuan city, in the Ningxia province of China. RESULTS: Sexual dimorphism of 2D:4D and HGS were found, males had significantly lower 2D:4D and greater HGS than females. 2D:4D in both hands were significantly negative correlated with HGS in females and not in males. CONCLUSIONS: 2D:4D ratio is negative correlated with HGS in a Chinese population of Ningxia Han ethnicity and this association should be considered on the anthropological research within an evolutionary concept in the future. PMID- 27685463 TI - Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages. AB - Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS) and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS). We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that alpha2-adrenoceptor, I1-imidazoline receptor or I2 imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation. PMID- 27685462 TI - Cytokine Patterns in Tuberculosis Infection; IL-1ra, IL-2 and IP-10 Differentiate Borderline QuantiFERON-TB Samples from Uninfected Controls. AB - BACKGROUND: Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values. METHODS: 27 soluble biomarkers were analysed in QFT supernatants from patients with active TB (n = 18), individuals with LTBI (n = 48) and from QFT negative controls (n = 16) by the Multiplex bead assay. The LTBI group was classified into two groups according to QFT IFN-gamma levels; QFT borderline (0.35-0.70 IU/mL, n = 11) or QFT high (>0.70 IU/mL, n = 36). RESULTS: The levels of IL-1ra, IL-2, IL-13, IL-15, IFN-gamma, IP 10 and MCP-1 in background corrected TB antigen stimulated supernatants (TBAg Nil) significantly distinguished both active TB and LTBI QFT high groups from the QFT negative controls (p<=0.004). In addition, IL-1ra, IL-2 and IP-10 significantly differentiated the QFT borderline group from the controls (p<=0.001). Still, in the QFT borderline group the IL-1ra and IP-10 levels were not significant different from neither the QFT high nor the active TB group, whereas the IL-2 levels were lower (p<=0.003). The level of IP-10 showed the best separation between the QFT borderline group and the QFT negative controls (AUC 0.92) and offered 100% sensitivity for active TB. CONCLUSION: IL-1ra, IL-2 and IP 10 differentiate QFT borderline samples from uninfected controls and the majority of QFT borderline subjects were classified as LTBI by these markers. Still, inconsistency was seen, and further studies are needed to examine the performance of alternative markers before concluded if they could be used as diagnostics tools. PMID- 27685465 TI - Predictors for everyday functioning in preschool children born preterm and at term. PMID- 27685466 TI - Micropatterning and Assembly of 3D Microvessels. AB - In vitro platforms to study endothelial cells and vascular biology are largely limited to 2D endothelial cell culture, flow chambers with polymer or glass based substrates, and hydrogel-based tube formation assays. These assays, while informative, do not recapitulate lumen geometry, proper extracellular matrix, and multi-cellular proximity, which play key roles in modulating vascular function. This manuscript describes an injection molding method to generate engineered vessels with diameters on the order of 100 um. Microvessels are fabricated by seeding endothelial cells in a microfluidic channel embedded within a native type I collagen hydrogel. By incorporating parenchymal cells within the collagen matrix prior to channel formation, specific tissue microenvironments can be modeled and studied. Additional modulations of hydrodynamic properties and media composition allow for control of complex vascular function within the desired microenvironment. This platform allows for the study of perivascular cell recruitment, blood-endothelium interactions, flow response, and tissue microvascular interactions. Engineered microvessels offer the ability to isolate the influence from individual components of a vascular niche and precisely control its chemical, mechanical, and biological properties to study vascular biology in both health and disease. PMID- 27685468 TI - The Angle Labor Pain Questionnaire: Reliability, Validity, Sensitivity to Change, and Responsiveness During Early Active Labor Without Pain Relief. AB - OBJECTIVES: The Angle Labor Pain Questionnaire (A-LPQ) is a new, condition specific, multidimensional psychometric instrument that measures the most important dimensions of women's childbirth pain experiences using 5 subscales: The Enormity of the Pain, Fear/Anxiety, Uterine Contraction Pain, Birthing Pain, and Back Pain/Long Haul. This study assessed the A-LPQ's test-retest reliability during early active labor without pain relief. METHODS: Two versions of the A-LPQ were randomly administered to laboring women during 2 test sessions separated by a 20-minute window. Participants were of mixed parity, contracting >=3 minutes apart, cervical dilation <=6 cm, and without pain relief. Changes in pain were rated using the Patient Global Impression of Change Scale. Overall pain intensity and pain coping were rated using the Numeric Rating Scale (NRS) and the Verbal Rating Scale (VRS) and the Pain Mastery Scale (PMS) respectively. A-LPQ test retest reliability (primary outcome), Cronbach's alpha, and concurrent validity with NRS, VRS, and PMS scores were assessed (n=104). Responsiveness was assessed in 55 women who reported changes in pain. RESULTS: A-LPQ summary and subscale scores demonstrated good test-retest reliability (ICCs, 0.96 to 0.89), trivial to moderate sensitivity to change, and high responsiveness to minimal changes in pain (0.85 to 1.50). Cronbach's alpha for A-LPQ summary scores was excellent (0.94) and ranged from 0.72 to 0.94 for subscales. Concurrent validity was supported by moderate to strong correlations with NRS and VRS scores for overall pain intensity and PMS scores for pain coping. DISCUSSION: Findings support A-LPQ use for assessing women's childbirth pain experiences. PMID- 27685467 TI - Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination. AB - A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration. PMID- 27685469 TI - Potassium-Mediated Hydrophosphorylation of Heterocumulenes with Diarylphosphane Oxide and Sulfide. AB - The preparation of the hydrophosphorylation catalysts succeeds via the metalation of dimesitylphosphane oxide and diphenylphosphane sulfide with potassium hydride in ethereal solvents such as tetrahydropyran (THP) and tetrahydrofuran (THF) yielding the tetramers [(thp)K(OPMes2)]4 (1a) and [(thf)3{K(OPMes2)}4] (1b) as well as [(thp)KSPPh2]infinity (2) with a strand-like structure in the crystalline state. In ethereal solution these complexes very slowly degrade into KPAr2 and KE2PAr2 (E = O, S). The catalytic conversion of iPr-N?C?E' (E' = O, S) and of R N?C?N-R (R = iPr, cHex) to the addition products Ar2P(E)-C(=E')-NHR (Ar = Ph, Mes; E = O, S; E' = O, S, NR) was studied in the presence of catalytic amounts of Ar2PEK (Ar = Ph, Mes; E = O, S). Steric hindrance prevents the addition of dimesitylphosphane oxide to N,N'-diisopropylcarbodiimide, whereas diphenylphosphane oxide and sulfide smoothly add to iPr-N?C?N-iPr yielding Ph2P(E)-C(?N-iPr)-NHiPr (E = O, S). PMID- 27685470 TI - Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota. AB - In this study we determined protein and gene expression in the caeca of newly hatched chickens inoculated with cecal contents sourced from hens of different ages. Over 250 proteins exhibited modified expression levels in response to microbiota inoculation. The most significant inductions were observed for ISG12 2, OASL, ES1, LYG2, DMBT1-L, CDD, ANGPTL6, B2M, CUZD1, IgM and Ig lambda chain. Of these, ISG12-2, ES1 and both immunoglobulins were expressed at lower levels in germ-free chickens compared to conventional chickens. In contrast, CELA2A, BRT-2, ALDH1A1, ADH1C, AKR1B1L, HEXB, ALDH2, ALDOB, CALB1 and TTR were expressed at lower levels following inoculation of microbiota. When chicks were given microbiota preparations from different age donors, the recipients mounted differential responses to the inoculation which also differed from the response profile in naturally colonised birds. For example, B2M, CUZD1 and CELA2A responded differently to the inoculation with microbiota of 4- or 40-week-old hens. The increased or decreased gene expression could be recorded 6 weeks after the inoculation of newly hatched chickens. To characterise the proteins that may directly interact with the microbiota we characterised chicken proteins that co purified with the microbiota and identified a range of host proteins including CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda. We propose that induction of ISG12-2 results in reduced apoptosis of host cells exposed to the colonizing commensal microbiota and that CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda reduce contact of luminal microbiota with the gut epithelium thereby reducing the inflammatory response. PMID- 27685471 TI - NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain. AB - BACKGROUND: Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain. METHODS: We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014-2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer. Additionally, clade information for genotype 1a was obtained by using the software geno2pheno (http://hcv.geno2pheno.org/). RESULTS: In total, 875 out of 2568 samples were from human immunodeficiency virus (HIV)/HCV-coinfected patients. Q80K was the main RAV found in our patients (11.1%) and the rest of the resistance-associated variants had a lower frequency, including S122G (6.23%), T54S (3.47%), V55A (2.61%), and V55I (2.15%), which were among the most frequent after Q80K. Overall, 286 samples had the Q80K polymorphism (11.1%) and 614 (23.9%) were GT1a clade I. HIV/HCV-coinfected patients had a higher frequency of Q80K and GT1a clade I than HCV-monoinfected patients (12.9% vs. 9.6% [p = 0.012] and 28.5% vs. 21.4% [p<0.001], respectively). Both the prevalence of Q80K and GT1a clade I were not uniform throughout the country (p<0.001), which ranged from 7.3%-22.2% and 15.7%-42.5%, respectively. The frequency of the Q80K polymorphism was far higher in patients infected with GT1a clade I than in patients infected with GT1a clade II (41.5% vs. 1.6%; p<0.001). CONCLUSIONS: The prevalence of most resistance-associated variants in NS3 was low in patients infected with HCV GT1a in Spain, except for Q80K (11.1%), which was also notably higher in HIV/HCV-coinfected patients. The vast majority of Q80K polymorphisms were detected in GT1a clade I. PMID- 27685472 TI - Illegal use patterns, side effects, and analytical methods of ketamine. AB - In Asian countries, such as China, Taiwan, and Hong Kong, ketamine (KT) is one of the most prevalent illicit use drugs. KT is regulated by various drug-related laws in many countries, such as Korea, Taiwan, China, U.S.A, Netherlands, UK, Australia, Mexico, and Canada. This review research explored pharmacology and side effects of KT, the illicit use patterns of KT, the analytical methods of KT in biological samples, and the concentrations of KT from abusers and non-abusers. Many side effects of KT have been reported mental and physical problems. Although many studies conducted various analytical methods for KT, this research focused on the urine and hair analysis and compared some parameters of samples, instruments, columns, extraction methods, internal standards, LOD/LOQ levels, metabolites, NK/K ratio, cut off values, and m/z values. Our research also compared the concentrations of KT in biological samples from abusers and non abusers. Many rapid and precise analytical methods for illegal KT use are needed to be developed and applied to real samples. To minimize and prevent harm from KT, the authorities and appropriate agencies require a careful assessment, evaluation, early identification, and surveillance of KT users in both clinical and social settings. In addition, there is a need to construct a stricter legislative management and provide preventive education to younger individuals because illegal KT use is relatively common among the young populations. PMID- 27685475 TI - Exploring the Catalytic Mechanism of Human Glutamine Synthetase by Computer Simulations. AB - Glutamine synthetase is an important enzyme that catalyzes the ATP-dependent formation of glutamine from glutamate and ammonia. In mammals, it plays a key role in preventing excitotoxicity in the brain and detoxifying ammonia in the liver. In plants and bacteria, it is fundamental for nitrogen metabolism, being critical for the survival of the organism. In this work, we show how the use of classical molecular dynamics simulations and multiscale quantum mechanics/molecular mechanics simulations allowed us to examine the structural properties and dynamics of human glutamine synthetase (HsGS), as well as the reaction mechanisms involved in the catalytic process with atomic level detail. Our results suggest that glutamine formation proceeds through a two-step mechanism that includes a first step in which the gamma-glutamyl phosphate intermediate forms, with a 5 kcal/mol free energy barrier and a -8 kcal/mol reaction free energy, and then a second rate-limiting step involving the ammonia nucleophilic attack, with a free energy barrier of 19 kcal/mol and a reaction free energy of almost zero. A detailed analysis of structural features within each step exposed the relevance of the acid-base equilibrium related to protein residues and substrates in the thermodynamics and kinetics of the reactions. These results provide a comprehensive study of HsGS dynamics and establish the groundwork for further analysis regarding changes in HsGS activity, as occur in natural variants and post-translational modifications. PMID- 27685473 TI - Blood concentrations of new designer benzodiazepines in forensic cases. AB - INTRODUCTION: A number of new designer benzodiazepines have reached the illegal drug market over the past years. Toxicological interpretation of concentrations of these drugs in blood is quite challenging as very limited human data have previously been published. The aim of this study was to report blood concentrations of new designer benzodiazepines in a population of drugged drivers as well as some other criminal offenders, and to relate this to clinical impairment. METHODS: The present material represents cases involving new designer benzodiazepines (clonazolam, diclazepam, flubromazepam, flubromazolam and pyrazolam) and etizolam, submitted for analyses during the period July 1, 2013 May 31, 2016. Analyses were performed using an ultra-performance liquid chromatography-tandem mass spectrometry method. Blood concentrations and results from the clinical test of impairment are reported. RESULTS: New designer benzodiazepines were detected in 77 cases during the study period. The median (range) concentrations were 0.012mg/L (0.00048-0.10) for flubromazolam (n=25), 0.055mg/L (0.0047-1.2) for flubromazepam (n=24), 0.013mg/L (0.0021-0.057) for diclazepam (n=15), 0.050mg/L (0.019-0.17) for etizolam (n=14), 0.0053mg/L (0.0019 0.011) for clonazolam (n=7) and 0.074mg/L for pyrazolam (n=1). In six cases, designer benzodiazepines were the only drugs detected in blood, and in two of those cases, the physician had given the conclusion of "considerably impaired" upon performing the clinical test for impairment. CONCLUSION: Given the lack of previously published data on human concentrations, results presented in this study could be helpful in interpretation of blood concentrations of new designer benzodiazepines. This is crucial for the assessment of the importance of toxicological results in suspected drugged drivers, rape victims, etc. PMID- 27685477 TI - Recognition and Management of Shaken Baby Syndrome. PMID- 27685474 TI - Nitrobenzodiazepines: Postmortem brain and blood reference concentrations. AB - Reference concentrations are needed to evaluate postmortem toxicology results and usually femoral blood is the specimen of choice. However, brain tissue has been suggested as a viable alternative specimen, since postmortem blood concentrations can be difficult to interpret due to postmortem redistribution, among other factors. Here we present reference concentrations of postmortem brain and femoral blood of the nitrobenzodiazepines clonazepam, flunitrazepam, and nitrazepam that are of particular interest since they commonly are converted to their corresponding 7-aminometabolites in the postmortem situation. The drugs and metabolites were quantified in both matrices using LC-MS-MS in 69 cases. In 63 cases the compounds were judged not to have been of significance for the death (C cases), whereas they were considered to have been a contributing factor in 6 cases (B cases). No cases were observed with a nitrobenzodiazepine being the sole cause of death (A cases). The brain-blood ratios for clonazepam and nitrazepam were 5.5 and 4.7, respectively, while the brain-blood ratios for the 7 aminometabolites ranged from 0.4 to 0.5. Flunitrazepam only occurred as the 7 aminometabolite. A positive correlation between brain and blood concentrations was found with Spearman's rank correlation coefficients (rs) ranging from 0.77 to 0.96. The measured femoral blood concentrations agree with literature values, but only few brain concentrations were available for comparison. The drug-metabolite ratios for clonazepam and nitrazepam were 10-12 times higher in brain than in blood. The pre-analytical variation in brain of 5.9% was fairly low, suggesting that brain tissue is a useful alternative to blood. The reported brain and femoral blood concentrations serve as reference values in postmortem investigations. PMID- 27685476 TI - Resident Working Hours and Outcome Measures. PMID- 27685478 TI - Smoking Behaviour Among People Living with HIV and AIDS: A Sub-Group Comparison. AB - Recent advancements in the treatment of HIV have significantly improved long-term health outcomes and life expectancy among people living with HIV/AIDS. As such, healthcare professionals have begun to focus more seriously on health protective behaviour changes that could further reduce mortality including smoking and tobacco dependence. A cross-sectional survey was conducted with 438 people living with HIV/AIDS (PLWHA) attending a clinic in an urban area to measure current smoking behaviours. After removing missing data, the final sample was 402 service users. Among those surveyed 141 (35.0%) were current smokers with 35 (8.2%) ex smokers. Rates among key sub-groups were higher. Comparatively, smoking prevalence was very low among African migrants (8, 7.2%), particularly African born women (1, 1.3%). In line with international studies, smoking prevalence among PLWHA was nearly double that of the general population. These findings come at a time when smoking in the general population in Ireland is at an all-time low, making the need to address tobacco dependence among PLWHA all the more vital. PMID- 27685479 TI - Dedicated Orthogeriatric Service Saves the HSE a Million Euro. AB - Hip fracture is common in older adults and is associated with high morbidity, mortality and significant health care costs. A pilot orthogeriatrics service was established in an acute hospital. We aimed to establish the cost effectiveness of this service. Length of hospital stay, discharge destination and rehabilitation requirements were analysed for a one year period and compared to patients who received usual care prior to the service. We calculated the costs incurred and savings produced by the orthogeriatric service. Median length of stay was reduced by 3 days (p < 0.001) saving ?266,976. There was a 19% reduction in rehabilitation requirements saving ?192,600. Median rehabilitation length of stay was reduced by 6.5 days saving ?171,093. Reductions in long term care requirements led to savings of ?10,934 per week. Costs to establish such a service amount to ?171,564. The introduction of this service led to improved patient outcomes in a cost effective manner. PMID- 27685480 TI - Standardised versus Individualised Parenteral Nutrition. Further Food for Thought. AB - Parenteral Nutrition may be prescribed as a standard PN (SPN) formulation or as an individualised PN (IPN) formulation. SPN may have advantages in terms of rapid availability, less prescription errors, decreased risk of infection and cost savings but IPN, specifically tailored to an infants needs, may achieve better outcomes in terms of nutrient intake and weight gain. The aim of our study was to determine if VLBW infants in our NICU benefited from receiving IPN over currently available SPN solutions. Our findings were that VLBW infants prescribed IPN received significantly more amino acid (28%), glucose (6%), energy (11%) and calcium (8%) from the aqueous phase of PN than had they received a similar volume of SPN. The benefits were seen over all the days for which PN was administered. In conclusion, IPN was found to offer significant benefits to our VLBW infants. Modifications to currently available SPN would result in better SPN formulations. Our study also supported the recent recommendation to reduce the calcium:phosphate ratio in PN solutions to avoid early hypophosphataemia. PMID- 27685481 TI - Irish Medical Students Understanding of the Intern Year. AB - Upon completion of medical school in Ireland, graduates must make the transition to becoming interns. The transition into the intern year may be described as challenging as graduates assume clinical responsibilities. Historically, a survey of interns in 1996 found that 91% felt unprepared for their role. However, recent surveys in 2012 have demonstrated that this is changing with preparedness rates reaching 52%. This can be partially explained by multiple initiatives at the local and national level. Our study aimed evaluate medical student understanding of the intern year and associated factors. An online, cross-sectional survey was sent out to all Irish medical students in 2013 and included questions regarding their understanding of the intern year. Two thousand, two hundred and forty-eight students responded, with 1,224 (55.4%) of students agreeing or strongly agreeing that they had a good understanding of what the intern year entails. This rose to 485 (73.7%) among senior medical students. Of junior medical students, 260 (42.8%) indicated they understood what the intern year, compared to 479 (48.7%) of intermediate medical students. Initiatives to continue improving preparedness for the intern year are essential in ensuring a smooth and less stressful transition into the medical workforce. PMID- 27685482 TI - Foot Drop: Looking Beyond Common Peroneal Nerve Palsy: A Neurophysiology Centre Experience. AB - Foot drop is a complex symptom with a considerable range in aetiology, severity and prognosis. We aim to characterise the aetiologies of foot drop and assess the diagnostic contribution of neurophysiologic testing (NCS/EMG). Retrospective review of consecutive referrals of foot drop to the Neurophysiology Department in Cork University Hospital was performed over a two year period (January 2012 to December 2013). Of a total of 59 referrals, common peroneal nerve (CPN) palsy comprised only slightly more than half of cases; 3(5%) have central origin; 3(5%) have motor neuron disease. Six (10%) have diabetes; 7(12%) have cancer; 5(8%) were bilateral. NCS/EMG altered initial working diagnosis in 14 out of 52 (27%) cases whereby initial diagnosis was provided. However one-third of all cases revealed additional coexistent pathology in an anatomic location remote to that of the primary diagnosis. Foot drop with central and proximal localisations are important and under recognised. NCS/EMG is valuable and also reveals additional pathology which warrants investigation. PMID- 27685484 TI - Cows Milk Allergy: A Cohort of Patients from a University Hospital. AB - The study illustrates advantages of Fiberoptic Bronchoscopy, a new service started at St. Lukes General Hospital in patient care since April 2014. Retrospective review of Bronchoscopies and referrals to Tertiary care unit for Bronchoscopy, prior and after initiation of service at St. Lukes Hospital were studied. Total 106 procedures were performed out of which 103(98%) were for diagnostic purpose. Common Indications for bronchoscopy were functional airway assessment in 38 cases (35%) of chronic cough, 26 cases (24.8%) of suspected Malignancy. The average time taken for procedure was 15 + 1 minute with overall rate of complication recorded in 1 case (0.95%). 32(30%) inpatients were referred before Bronchoscopy services were started locally.15(14%) patients were referred for Endobronchial ultrasound (EBUS) after diagnostic procedure performed at St. Lukes Hospital. To conclude, Bronchoscopy is a safe procedure used for diagnosis of various Lung conditions. The services offered locally reduced the time and cost involved in referrals. The diagnostic Bronchoscopies performed for Malignancy at St. Lukes Hospital have rightly increased references for EBUS at Tertiary care Unit. PMID- 27685483 TI - Profile of Frequent Attenders to a Dublin Inner City Emergency Department. AB - A retrospective review of the demographics, co-morbidities and substance misuse of the 20 most frequent presenters to the Mater Misericordiae University Hospital emergency department during 2014 was carried out in an attempt to better understand the epidemiology of their presentations. Eighty-five percent were male and 15% female (p<0.001). The average age was 40.6 years with a median 38.5 years. All were unemployed and 7 (35%) had no fixed abode. Thirteen patients (65%) lived an average of 4.5 kilometres from the ED. In this study the presence of a mental illness, homelessness, alcohol or drug misuse were associated with significantly higher attendance rates (p=0.001, p<0.001, p<0.05, p<0.001 respectively). Early identification of these patients and targeting them for effective case-based community-led treatment strategies could improve their quality of life, decrease their cost of care and ultimately lead to more effective utilisation of our already overburdened emergency departments. PMID- 27685485 TI - The Evolution of Spinal Surgery in the West of Ireland, 2005-2013. AB - The aim of this study was to determine the changes in both the short and long term, in the trends within the practice of spinal surgery in Galway University Hospitals (GUH) over a seven year period, January 2005 to January 2013. The absolute number of spinal surgery cases has increased from 147 in 2005, to 257 cases by 2013. Multiple level spine surgery accounts for 51% (131) of all cases by 2013, which is an increase from 31% (45) in 2005. On analysis of the trends within spinal surgery during the study period, a statistically significant (p<0.05) increase in all aspects of spinal surgery was noted, with the exception of surgeries for single level, lumbar and infection pathology respectively. The average waiting time for lumbar decompression and instrumentation climbed for an average of 1.3 months in 2008 to 12.1 months by 2012.The volume and complexity of spinal surgery has increased during the study period, in the West of Ireland. PMID- 27685486 TI - Transient Hyperphosphatasaemia of Infancy: An Often Unrecognised and Thus Over Investigated Condition. AB - Transient hyperphosphatasaemia of infancy (THI) is a benign condition characterised by a rapid rise and fall in plasma alkaline phosphatase (ALP) activity without biochemical or clinical evidence of underlying bone or liver disease. It is most often identified incidentally during routine blood testing; hence it is important to recognise this phenomenon in order to avoid unnecessary investigations and inappropriate referrals. This review has provided some useful insight into the characteristics associated with the THI and the routine clinical practice when isolated elevation of plasma ALP is found in patients at two sites in Republic of Ireland. Over a period of two years, 107,468 requests for plasma ALP analysis were received, of which a total of 250 patients were identified with a plasma ALP activity above 1000IU/L. The biochemical diagnosis of THI was considered in 62 patients, 15 (25%) of these were inappropriately investigated and 5 (13%) were unnecessarily referred to tertiary care by their general practitioners. We recommend that if an isolated high plasma ALP activity is detected during routine blood testing without any indication of bone or liver disease, it is important to consider THI in the differential diagnosis and to repeat the plasma ALP in 7-10 days. This should be further confirmed by the normalisation of the plasma ALP activity in 2-3 months or by ALP isoenzyme analysis where deemed appropriate by the laboratory. PMID- 27685487 TI - The Practice of Vitamin D Deficiency Assessment in a Geriatric Day Hospital. AB - There has been no clear consensus on the assessment and treatment of vitamin D deficiency prior to the publication of the National Osteoporosis Society (NOS) Vitamin D Guideline in 2014. The aim of our study was to assess the practice in a medicine for the older person day hospital setting relative to this guideline. A 6-month retrospective analysis of all new patients who attended service from January to July 2013 was carried out. Seventy-six patients were included in the final analysis. Mean age was 83 years. 39 (51%) patients had sufficient levels while 37 (49%) patients had insufficient levels; 14 (19%) being inadequate and 23 (30%) deficient. Eighteen patients who had insufficient levels were subsequently prescribed supplements; 13 (72%) received vitamin D3 in combination with calcium while 5 (28%) received vitamin D3 alone. Based on the findings of this study, we have made some recommendations and adopted the guideline. PMID- 27685488 TI - Early Pregnancy Ultrasound and Management: Effect of a Multifaceted Training on Physician Knowledge. AB - Vaginal bleeding is a common event in early pregnancy, with 20-40% of pregnancies affected. Prompt diagnosis and management of bleeding is important, both to reduce morbidity and to avoid excessive emotional distress. This was a prospective study of an educational programme aimed at Obstetrics and Gynaecology BST trainees in the National Maternity Hospital, Dublin. The educational programme consisted of didactic lectures, and simulation and practical sessions. A questionnaire reviewing early pregnancy complications was used to assess participant knowledge. Six trainees participated in the programme, with five (83%) answering the questionnaire. The pre-education questionnaire showed a generally poor level of knowledge of early pregnancy complications with 8/50 (16%) questions answered correctly. Following the educational intervention there was a statistically significant increase in participant knowledge with 45/50 (90%) questions answered correctly. A significant increase in participant knowledge of early pregnancy complications followed our multifaceted educational programme. Study limitations exist, however we have shown the potential value of our educational programme. PMID- 27685489 TI - Which Organ is Responsible for the Pathogenesis of Obesity? AB - Obesity is associated with significant complications and healthcare costs, but our ability to treat obesity has been limited by our understanding of its pathogenesis. We surveyed diabetologists and obesity related health care professionals asking them which organ they believed to be responsible for the pathogenesis of obesity. Participants favoured a central nervous system (CNS) aetiology. The response echoes evidence from genome wide association studies identifying a link between obesity and CNS loci. Our most successful obesity therapies involve the manipulation of subcortical area of the brain involved in energy balance. Future success in the management of obesity will be determined by our ability to define the pathogenesis of the disease in individual cases, moving from a one-size-fits-all, to more focused interventions. PMID- 27685490 TI - Mycobacterium avium complex pulmonary disease: characteristics and treatment in an Irish patient cohort. AB - The prevalence of Mycobacterium avium complex (MAC) pulmonary disease is increasing globally. However, reliable national and international data relating to its epidemiology and management is lacking. During the period 2003-2014, MAC was isolated from the pulmonary samples of 75 patients at the Irish Mycobacteria Reference Laboratory (IMRL). Most patients (42, 56%) had underlying pulmonary disease, and 37 (49%) had clinical/radiographic characteristics consistent with MAC pulmonary disease. However, only 18 patients (24%) fulfilled internationally accepted criteria for diagnosis/treatment of this disease. Treatment was started in 13 (72%) of these cases, which is similar to internationally published treatment rates. The diagnosis of significant MAC pulmonary disease can be difficult, and treatment is not always warranted even when diagnostic criteria are met. PMID- 27685493 TI - Progressive Contractures due to Eosinophilic Fasciitis in a 17 year old Male. PMID- 27685492 TI - First reported finding of a Malignant Pleural Mesothelioma in a patient post Liver Transplant. AB - The case history of a liver transplant recipient is presented, who presented with acute dyspnoea after an innocuous fall. His early management was complicated and he was eventually diagnosed with malignant mesothelioma. This is the first such case report in the literature. PMID- 27685491 TI - Pre-Hospital Fast Positive Cases Identified by DFB Ambulance Paramedics: Final Clinical Diagnosis. AB - Ischaemic stroke clinical outcomes are improved by earlier treatment with intravenous thrombolysis. An existing pathway at the Mater University Hospital for assessment of suspected acute stroke in the Emergency Department was updated, aiming to shorten door-to-needle time. This study examines the final clinical diagnosis of Dublin Fire Brigade Ambulance Paramedic identified Face-Arm-Speech Test (FAST) positive patients presenting to the Emergency Department over a 7 month period. A retrospective analysis was carried out of 177 consecutive FAST positive patients presenting between March and November 2014. The final clinical diagnosis was acute stroke in 57.1% (n=101) of patients. Of these, 76 were ischaemic strokes of whom 56.5% (n=43) were thrombolysed. In the pre-hospital setting Ambulance Paramedics can identify, with reasonable accuracy, acute stroke using the FAST test. Over half of the ischaemic stroke patients presenting via this pathway can be treated with intravenous thrombolysis. PMID- 27685494 TI - Lyme disease in modern Ireland: the importance of home imaging. PMID- 27685495 TI - An Audit of Paediatric Prescribing of Amoxicillin. PMID- 27685497 TI - Tuberculosis in India: a case of innovation and control, by Nora Engel. PMID- 27685496 TI - Asymmetric Synthesis of Homocitric Acid Lactone. AB - A short, diastereoselective synthesis of homocitric acid lactone is described. The key step is a bioinspired aldol addition to set the stereogenic center in an intermediate that requires only modest oxidation state manipulation to complete the synthesis. This approach enables rapid generation of isotopomers in which carbon and hydrogen can be replaced by heavier nuclei at nearly every position. PMID- 27685498 TI - A CASE OF CONE DYSTROPHY ASSOCIATED WITH CHOROIDAL NEOVASCULARIZATION. AB - PURPOSE: To report a case of choroidal neovascularization (CNV) in a patient with cone dystrophy (CD). METHODS: Case report. RESULTS: A 20-year-old woman presented with diminished vision in her right eye. Fundus examination showed perifoveal retinal pigment epithelial changes and retinal hemorrhage consistent with subretinal CNV in the right eye, and mild retinal pigment epithelial changes with a dull foveal reflex in the left eye. Optical coherence tomography analysis and fundus fluorescein angiography also confirmed the subfoveal CNV in the right eye. Electroretinography showed decreased amplitudes in photopic and 30-Hz flicker tests in both eyes, which confirmed cone dystrophy. A single intravitreal ranibizumab injection resolved the edema and stabilized the CNV during the follow up of 6 months. CONCLUSION: Cone dystrophy is an inherited ocular disorder characterized by loss of cone photoreceptors. Association of CNV has been reported in patients with fundus flavimaculatus, best dystrophy, gyrate atrophy, choroideremia, retinitis pigmentosa, adult-onset foveomacular vitelliform dystrophy, Sorsby macular dystrophy, Bietti crystalline dystrophy, and myotonic dystrophy-related macular dystrophy. We report a case of a patient with CD in whom CNV developed in one eye and responded to a single ranibizumab injection. PMID- 27685499 TI - YOUNGEST REPORTED CASE OF MACULAR TELANGIECTASIA (MAC TEL) TYPE 2. AB - PURPOSE: To report the occurrence of macular telangiectasia (Mac Tel) Type 2 in a 28-year-old lady. METHODS: Retrospective case report. RESULTS: A 28-year-old obese diabetic lady presented with mild blurring of vision and reading difficulty for 2 months. Clinical examination revealed the presence of myopic refraction and features suggestive of macular telangiectasia Type 2 on fundus evaluation. Fundus fluorescein angiography and optical coherence tomography confirmed the diagnosis of Mac Tel Type 2, Stage 3. As there was no evidence of subretinal neovascular membrane, she was advised to follow-up regularly. CONCLUSION: Mac Tel Type 2 or idiopathic juxtafoveal telangiectasia is a condition commonly reported in middle age or elderly people. Presentation in a young individual alerts us to the possibility of this condition occurring at an early age and also stresses on the need for meticulous examination to detect subtle signs of the condition in the young. PMID- 27685500 TI - FOVEAL HYPOPLASIA: DIAGNOSIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. AB - PURPOSE: To describe the clinical presentations and image findings of a patient with foveal hypoplasia. METHODS: Observational case report of one patient. The clinical presentation of the patient was documented by fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 55-year-old healthy white female with bilateral foveal hypoplasia without nystagmus was presented. There were no signs suggestive of ocular albinism. Absence of foveal depression was noted on both clinical examination and optical coherence tomography. Lack of foveal avascular zone was confirmed on fluorescein angiography and optical coherence tomography angiography. CONCLUSION: To the best of our knowledge this is the first report of findings in foveal hypoplasia examined by angio-optical coherence tomography. Optical coherence tomography angiography is an easy, rapid, and noninvasive tool that allows imaging of the retinal microvasculature without intravenous dye injection. PMID- 27685501 TI - RETINAL VASCULAR TORTUOSITY AND EXUDATIVE RETINOPATHY IN A FAMILY WITH DYSKERATOSIS CONGENITA MASQUERADING AS FAMILIAL EXUDATIVE VITREORETINOPATHY. AB - PURPOSE: To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy. METHODS: Observational case series involving single family and literature review. RESULTS: A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Both patients were managed with laser photocoagulation. Eight years after the initial presentation, both siblings developed pancytopenia secondary to bone marrow failure. Laboratory work-up revealed severely shortened telomere length in both patients, and genetic testing revealed a missense mutation in the gene that encodes the reverse transcriptase component of telomerase, confirming the diagnosis of dyskeratosis congenita. The father of both children was a carrier of the same mutation, who exhibited marked retinal vascular tortuosity of the second-order vessels. CONCLUSION: Dyskeratosis congenita is a severe multisystem disorder, which should be considered in cases of pediatric exudative retinopathies with concurrent signs and/or symptoms of bone marrow failure. PMID- 27685502 TI - RETINAL DETACHMENT ASSOCIATED WITH PERIPHERAL TEAR OF THE RETINAL PIGMENT EPITHELIUM IN PACHYCHOROID SPECTRUM DISEASE. AB - PURPOSE: To describe a rare case of an exudative retinal detachment associated with a peripheral tear of the retinal pigment epithelium in a young myopic pachychoroid eye. METHODS: Clinical case report and literature review. Imaging was obtained with color fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fluorescein angiography. RESULTS: A 33 year-old white man presented with an exudative choroidopathy resulting in an exudative neurosensory detachment, associated with peripheral retinal pigment epithelium tears. Spectral domain optical coherence tomography demonstrated a pachychoroid (628 MUm) with subfoveal fluid. Despite a secondary pars-plana vitrectomy with silicone oil and later, Densiron-68 (Labtician Ophthalmics Inc) endotamponade, there was an area of persistent subretinal fluid inferiorly. A previously placed scleral buckle was removed, and scleral window surgery performed, with complete resolution of fluid and restoration of vision. Choroidal thickness improved to 333 MUm postoperatively. CONCLUSION: Peripheral retinal pigment epithelium tear-associated retinal detachment can be seen in patients with pachychoroid spectrum disease. Scleral window surgery may be considered in the management of these retinal detachments. PMID- 27685503 TI - Heterodiazocines: Synthesis and Photochromic Properties, Trans to Cis Switching within the Bio-optical Window. AB - Diazocines, bridged azobenzenes, exhibit superior photophysical properties compared to parent azobenzenes such as high switching efficiencies, quantum yields, and particularly switching wavelengths in the visible range. Synthesis, however, proceeds with low yields, and derivatives are difficult to prepare. We now present two heterodiazocines which are easier to synthesize, and the general procedures should also provide facile access to derivatives. Moreover, both compounds can be switched with light in the far-red (650 nm). Accessibility and photophysical properties make them ideal candidates for applications such as photoswitchable drugs and functional materials. PMID- 27685504 TI - Affinity Labeling Detection of Endogenous Receptors from Zebrafish Embryos. AB - By combining the powers of Affinity Labeling and Immunoprecipitation (AFLIP), a technique for the detection of low abundance receptors in zebrafish embryos has been implemented. This technique takes advantage of the selectivity and sensitivity conferred by affinity labeling of a given receptor by its ligand with the specificity of the immunoprecipitation. We have used AFLIP to detect the type III TGF-beta receptor (TGFBR3), also know as betaglycan, during early zebrafish development. AFLIP was instrumental in validating the efficacy of a TGFBR3 morphant zebrafish phenotype. In the first step, embryo protein extracts are prepared and used to generate 125I-TGF-beta2-TGFBR3 complexes that are purified by immunoprecipitation. Later, these complexes are covalently cross-linked and revealed using SDS-PAGE separation and autoradiography detection. This technique requires the availability of a labeled ligand for, and a specific antibody against, the receptor to be detected, and shall be easily adapted to identify any growth factor or cytokine receptor that meets these requirements. PMID- 27685505 TI - Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view. AB - Self-emulsifying drug delivery system (SEDDS) is an isotropic mixture of lipid, surfactant and co-surfactant, which forms a fine emulsion when comes in contact of an aqueous medium with mild agitation. SEDDS is considered as a potential platform for oral delivery of hydrophobic drug in order to overcome their poor and irregular bioavailability challenges. In spite of fewer advantages like improved solubility of drug, bypassing lymphatic transport etc., SEDDS faces different controversial issues such as the use of appropriate terminology (self microemulsifying drug delivery system; SMEDDS or self-nanoemulsifying drug delivery system; SNEDDS), presence of high amount of surfactant, correlation of in vitro model to in vivo studies, lack of human volunteer study and effect of conversion of SEDDS to final administrable dosage form on pharmacokinetic behavior of the drug. In this review, potential issues or questions on SEDDS are identified and summarized from the pharmacokinetic point of view. Primarily this review includes the conflict between the influences of droplet size, variation in correlation between in vitro lipolysis or ex-vivo intestinal permeation and pharmacokinetic parameters, variation in in vivo results of solid and liquid SEDDS, and potential challenges or limitation of pharmacokinetic studies on human volunteers with orally administered SEDDS. In the past decades, hundreds of in vivo studies on SEDDS have been published. In the present study, only the relevant article on in vivo pharmacokinetic studies with orally administered SEDDS published in past 5-6 years are analyzed for an up to date compilation. PMID- 27685507 TI - The happiest place on earth. PMID- 27685508 TI - Anomalous abductor digiti minimi in Guyon canal: A cadaver study. AB - A routine cadaver dissection revealed a noteworthy anomalous muscle in the distal anterior forearm. Clinicians should be aware of this finding and consider it as a differential diagnosis in patients with wrist disorders such as ulnar tunnel syndrome from occlusion of the ulnar canal. A space-occupying lesion, such as the anomalous muscle found in this dissection, is an important potential source of ulnar canal obstruction. PMID- 27685509 TI - Letters to the Editor. PMID- 27685510 TI - Autism spectrum disorder. PMID- 27685511 TI - An urgent finding on a cervical spine MRI. AB - Cervical myelopathy is the most common spinal cord disorder in patients age 55 years and older in the United States. A high index of suspicion is critical for detecting early signs and symptoms and initiating early intervention, which directly correlates with better patient outcomes. PMID- 27685512 TI - An interesting case of intracerebral MRSA. AB - This article describes a patient whose intracerebral MRSA may have been caused by a spider bite to the thigh 2 months earlier. The patient's headache, nausea, and vomiting initially were thought to be caused by a high-grade glioma. Most brain abscesses have otogenic sources and are not from distant hematogenous spread. Although systemic antibiotics help with symptomatology, surgical eradication (when feasible) followed by IV antibiotics, provides definitive treatment. PMID- 27685513 TI - The inherited patient on opioids: A challenge for primary care clinicians. AB - Chronic pain is a common problem, affecting more than 100 million people in the United States, and primary care providers are highly likely to encounter patients on chronic opioid therapy. Initial encounters with a new patient already on high dose opioids can be difficult and lead to apprehension for both patient and provider. This article describes how to use current opioid prescribing guidelines, conduct a comprehensive pain assessment, and implement risk mitigation strategies to improve patient safety and effectively manage this patient population. PMID- 27685514 TI - The economic effect of a physician assistant or nurse practitioner in rural America. AB - Revenues generated by physician assistants (PAs) and NPs in clinics and hospitals create employment opportunities and wages, salaries, and benefits for staff, which in turn are circulated throughout the local economy. An input-output model was used to estimate the direct and secondary effects of a rural primary care PA or NP on the community and surrounding area. This type of model explains how input/output from one sector of industry can be the output/input for another sector. Given two example scenarios, a rural PA or NP can have an employment effect of 4.4 local jobs and labor income of $280,476 from the clinic. The total effect to a community with a hospital increases to 18.5 local jobs and $940,892 of labor income. PMID- 27685515 TI - The GMENAC report and the PA profession. AB - The 1980 report of the Graduate Medical Education National Advisory Committee (GMENAC) predicted a surplus of physicians by 1990 and 2000. The report appeared to have a depressing effect on the growth of the PA profession in the early 1980s; in the 9 years following its release, no new PA programs were started and a number of existing programs closed. The GMENAC forecast proved to be inaccurate and the PA profession saw significant program growth in the 1990s and beyond. A lesson of GMENAC is that accurately predicting health workforce supply and demand is difficult. PMID- 27685516 TI - An isolated hip fracture and groin pain in an older woman. PMID- 27685519 TI - What is causing this man's rectal pain and urinary retention? PMID- 27685517 TI - HINTS for differentiating peripheral from central causes of vertigo. AB - Dizziness and vertigo are common and difficult complaints encountered by providers. The differential diagnosis is large and varies from benign to life threatening disorders. The true challenge becomes differentiating benign peripheral vertigo from central vertigo. The HINTS examination can help differentiate peripheral from central causes of dizziness and vertigo. PMID- 27685520 TI - A distant close encounter. PMID- 27685521 TI - The use of proteomic technologies in breast cancer research. AB - The main findings in the field of breast cancer proteomic research as well as modern strategies, technologies and methods of validation are reviewed. A special attention is focused on validated proteomic biomarkers of breast cancer. The data on proteomic profiling of stroma, tumor microenvironment, involvement of proteins in tumor progression, invasion and metastasis, and mechanisms of action of new generation drugs, are analyzed. The results of proteomic analysis are of high clinical importance and significantly improve tumor molecular profiling, stratification of patients, screening, diagnostics, and therapy of breast cancer. PMID- 27685522 TI - Insights into the mechanism of natural terpenoids as NF-kappaB inhibitors: an overview on their anticancer potential. AB - The transcription factor, nuclear factor kappa B (NF-kB) is one of the principal inducible protein in mammals known to control the gene expression in many critical physiological responses such as oxidative stress, inflammation etc. and has been shown to play an important role in the pathogenesis of cancer. Terpenoids are major constituents present in nutritionally used fruits, vegetables and different spices which possess various pharmacological action including anticancer activity. Various terpenoids, viz. monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids, tetraterpenoids and polyterpenoids inhibit NF-kB signa-ling pathway through IkB phosphorylation, DNA binding, p65 translocation etc. Keeping in mind these facts, the present review revealed the anti-cancer potential of naturally occurring terpenoids highlighting their mechanism of NF-kB inhibition. This review also focuses on some of the naturally occurring terpenoids belonging to various chemical categories with potential inhibitory effects on NF-kB and their role in the treatment of cancer. PMID- 27685523 TI - Correlation of iodine symporter expression in highly and low malignant cell lines of human breast cancer differed in their sensitivity to doxorubicin. AB - To investigate the relationship of sodium/iodide symporter (NIS) expression with molecular phenotype of highly and low malignant cell lines of human breast cancer (BC) with different sensitivity to doxorubicin (Dox). MATERIALS AND METHODS: The cell lines used in the analysis included T47D, MCF-7, MDA-MB-231, MDA-MB-468, and MCF/Dox. NIS expression was studied by immunocytochemical method. RESULTS: The strongest iodine symporter expression (248 +/- 1.9; 272 +/- 3.2 and 289 +/- 2.8 points, respectively) were found in cells of highly malignant cell lines - MDA-MB 231, MDA-MB-468, and MCF-7/Dox. NIS expression was significantly weaker (< 120 points) in two BC cell lines of low malignancy (MCF-7 and T47D). In addition, the reduced sensitivity to Dox is associated with elevation of NIS expression in both high and low malignant cells. We have demonstrated correlations between NIS levels and certain indices of BC malignancy, namely proliferative activity (r = 0.51), receptor status (estrogen receptor; r = -0.47; and progesteron receptor; r = -0.47) and invasiveness (r = 0.46). CONCLUSIONS: Our data evidence that NIS expression level correlates with BC cells indices of malignancy and their sensitivity to Dox. The results obtained suggest the necessity for further studies of NIS expression in BC patients aimed at prognosing disease course and monitoring treatment efficacy with anthracyclines. PMID- 27685524 TI - Enterosorption combined with granulocyte colony stimulating factor decreases melphalan gonadal toxicity. AB - Today due to improvements in cancer treatment there is an increasing number of long-term cancer survivors, many of whom suffer from infertility caused by malignancy itself and chemo- or radiotherapy. Also, anticancer therapy may cause myelosuppression. Presently granulocyte colony stimulating factor (G-CSF) is used for prevention and treatment of myelosuppression. Another treatment option used to decrease intoxication and ameliorate side effects of cancer therapy is sorption technology. The aim of our investigation was to study the efficiency of combined use of enterosorption and G-CSF to decrease gonadal toxicity of chemotherapy. MATERIALS AND METHODS: Melphalan (L-PAM) injected i.v. at a single dose of 4 mg/kg to white inbred rats was used as gonadotoxic and myelosuppressing agent. Carbon enterosorbent C2 was administered by intragastric route as a suspension in saline at a dose of 5 ml per 1 kg of rats' body weight (or 900 mg/kg of the dry mass of enterosorbent) daily for 3 days before and for 7 days after L-PAM injection. G-CSF was injected once a day for 4 days starting from the next day after L-PAM administration at a dose of 50 ug/kg. Histological preparations of testicular tissues were examined by light microscopy. RESULTS: Our findings have shown that melphalan caused marked damage of testicular tissues and seminiferous, especially spermatogenic epithelium. The most expressed protection of the histological structure of testes was observed when enterosorbent and G-CSF were used in combination. CONCLUSION: Gonadal toxicity of chemotherapy could be efficiently decreased by the combined use of enterosorption and G-CSF. PMID- 27685525 TI - 2-Deoxy-D-glucose enhances dichloroacetate antitumor action against Lewis lung carcinoma. AB - Aerobic glycolysis that supports high proliferation rate and survival of tumor cells in unfavorable conditions is among fundamental features of tumor metabolism. The search for active modulators of energetic metabolism capable of suppressing tumor growth and metastasis could result in higher effectiveness of anticancer therapy. AIM: To study antitumor and antimetastatic activity of the modulators of energetic metabolism dichloroacetate (DCA) and 2-deoxy-D-glucose (2DG) used in combination treatment of Lewis lung carcinoma (LLC). MATERIALS AND METHODS: As experimental tumor model, LLC/R9 variant was used. DCA and 2DG were administered per os to S57Bl/6 mice 5 times per week for 3 weeks at a total dose of 1.5 and 0.98 g/kg, respectively, as single agents or in combination starting from the following day after tumor cell transplantation. Growth of primary tumor and number and volume of lung metastases were registered. Lactate and pyruvate content was determined by enzymatic methods using lactate dehydrogenase. Electron paramagnetic resonance was used for analyzing the functional state of the components of mitochondrial respiratory chain. Engulfing activity and reactive oxygen species (ROS) production in tumor-associated CD14(+) cells was analyzed by flow cytometer with the use of FITC-labeled staphylococcus, and by spectrofluorometry with the use of 2.7-dichlorofluorescein diacetate, respectively. RESULTS: DCA administered as a single agent did not affect primary tumor growth but decreased the number and volume of lung metastases by 60% (p < 0.05) and 90% (p < 0.05), respectively. In mice treated with 2DG only, primary tumor volume as well as the number and volume of lung metastases were not affected. Combination treatment with DCA and 2DG resulted in the decrease of primary tumor volume, the number and volumes of lung metastases by 70; 46, and 90%, respectively (p < 0.05). High antitumor activity of DCA + 2DG was associated with 31% decrease (p < 0.05) of lactate content in tumor tissue and 120% increase (p < 0.01) of ROS production in CD14(+) cells recruited to the region of tumor growth. CONCLUSION: 2DG that possesses neither antitumor nor antimetastatic activity against LLC/R9 significantly enhanced antitumor activity of DCA with accompanying inhibition of glycolysis and increase of cytotoxic activity of CD14(+) cells infiltrating tumor tissue. Taking into account significant antimetastatic activity of DCA this substance could be considered as a promising antimetastatic agent. PMID- 27685526 TI - Lactoferrin expression in breast cancer in relation to biologic properties of tumors and clinical features of disease. AB - To determine the patterns of lactoferrin (LF) expression in breast cancer (BC) in relation to biologic properties of the neoplasms and clinical features of the disease course. MATERIALS AND METHODS: Clinical specimens of 266 BC patients (115 patients with BC of stages I-II - retrospective study, and 151 BC patients - prospective study) were analyzed. Morphological, immunohistochemical and statistical methods were used. RESULTS: The number of LF-positive tumors in retrospective and prospective groups was similar (52.1 and 52.8%, respectively). Among common clinical criteria for prognosis of the disease outcome in BC patients (patient's age; stage of the disease; histological type, differentiation grade, receptor status; presence of metastases), a strong correlation was found only between expression indexes of LF and estrogen receptors (ER). In ER-positive tumors expression of LF was significantly higher than in ER-negative tumors (35 vs 18%). 5-Year survival rate of BC patients was higher in LF-positive group (70 vs 52% in LF-negative group). The presence of regional metastasis tended to correlate with an increased number of LF-positive tumors. In the patients with invasive ductal carcinoma, expression level of LF moderately correlated with occurrence of luminal A subtype (r = 0.43), while in the patients with invasive lobular carcinoma this index strongly correlated with occurrence of luminal B subtype (r = 0.71). LF expression correlated positively with low and moderate differentiation grade of luminal B or basal tumors, and negatively with luminal B or basal tumors of high differentiation grade (r = -0.57 and -0.63, respectively). CONCLUSION: It has been shown that LF expression in breast tumors correlated with life expectancy of BC patients and important physiologic and clinical features of the disease, while the character of such relation strongly depended on molecular phenotype of tumor, i.e. luminal A, luminal B or basal. PMID- 27685527 TI - The efficacy of tissue factor -603A/G and +5466A>G polimorphisms at the development of venous thromboembolism in cancer patients. AB - Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene -603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me-thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF -603A/G in the 5?upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using chi2 or Fisher exact test, if appropriate. RESULTS: No differences were observed in the distribution of TF gene -603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p < 0.05). Difference in frequency of 677TT+CT (MTHFR) + 5466GG (TF) genotypes combination was found in women of two investigated Groups (p < 0.05). No differences were also in genotypes and allele frequencies of MTHFR C677T and PT G20210A between two Groups (p > 0.05). CONCLUSIONS: The present study did not show significant association of TF gene 603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings. PMID- 27685528 TI - The effect of omega-fatty acids on mRNA expression level of PPARgamma in patients with gastric adenocarcinoma. AB - BACKGROUND: The antineoplastic role of peroxisome proliferator-activated receptor gamma (PPARgamma) ligandshas previously been demonstrated in several gastric cancer cell lines. Activation of PPARgamma by polyunsaturated fatty acids (PUFAs) inhibits growth and proliferationof tumor cells. In this double-blind clinical study, we evaluate the effect of PUFAs on PPARgamma mRNA expression in patients with gastric adenocarcinoma. MATERIALS AND METHODS: A total of 34 chemotherapy naive patients diagnosed with gastric adenocarcinoma were enrolled in the present study. According to treatment strategies, all subjects were divided into two groups, the first group (17 individuals) received cisplatin without supplements and the second group (17 individuals) received cisplatin plus orally administered PUFAs supplements for 3 weeks. The gastric biopsy samples were obtained from all participants before and after treatment, and PPARgamma mRNA expression levels were evaluated by quantitative real-time polymerase chain reaction using validated reference genes. RESULTS: Our findings revealed that PPARgamma mRNA expression is significantly upregulated in group II afterreceiving cisplatin plus orally administered PUFAs supplements for three weeks (p < 0.0001), whereas PPARgamma mRNA expression did not show significant alteration in group I after receiving cisplatin alone. CONCLUSION: The results of the study evidence that PPARgamma may act as a potential target for the therapy of human gastric adenocarcinoma. PMID- 27685529 TI - Chronic myeloid leukemia in patient with the Klinefelter syndrome. AB - AIM: Genetic inborn along with acquired diseases arise due to the lesions in genome of multipotent hematopoietic stem cells. The aim was to study an influence of constitutional anomaly, Klinefelter syndrome, and additional structural rearrangements on the BCR-ABL tyrosine kinase inhibitor targeted therapy efficacy. MATERIAL AND METHODS: We describe a 32-year-old male patient with chronic myeloid leukemia (CML) who was detected to have sex chromosomal abnormality during evaluation for Philadelphia chromosome. RESULTS: At diagnosis of CML, two clones were detected by standard cytogenetic investigation of bone marrow cells: 1) clone with translocation t(9;22)(q34;q11), with two sex X chromosomes and absence sex chromosome Y; 2) clone with t(9;22) and unbalanced t(Y;20)(q11;q13). Analysis of blast transformed lymphocytes from peripheral blood showed karyotype 47,XXY. Monitoring of targeted therapy with second generation inhibitor of BCR-ABL tyrosine kinase indicated a cytogenetic remission and absence of BCR-ABL1 fusion signals after 11 months. CONCLUSIONS: Absence of translocation t(9;22)(q34;q11) in blast transformed T-lymphocytes at diagnosis of CML evidences that this translocation may appear not only at the level of multipotent haemopoietic cell progenitors but also may have oligo lineage myeloid origin. Presence of additional structural chromosomal abnormality in the clone with t(9;22)(q34;q11) does not affect the efficacy of therapy with the use of second generation BCR-ABL tyrosine kinase inhibitor. PMID- 27685530 TI - Metastasis of two malignant tumors of different genesis in axillary lymph node (a case report). AB - This case report describes a rare clinical condition: metastasis of synchronous multiple primary tumors - skin melanoma and breast cancer in one axillary lymph node, confirmed with the results of clinical, morphological and immunohistochemical study of surgical material from 40 year-old woman. PMID- 27685532 TI - A rare clinical case of the isolated primary frontal bone osteoma. AB - AIM: To study a rare clinical case of isolated primary osteoma localized in the frontal bone, provide its detailed clinical and pathomorphological analysis, and evaluate statistical indicators of occurrence frequency and localization of facial skeleton osteomas during 2006-2015. MATERIALS AND METHODS: The retrospective case records analysis of patients undergoing treatment in the ma xillofacial department of Lviv Regional Clinical Hospital and suffering from facial skeleton osteomas was conducted. The clinical examination was carried out in accordance with the inspection protocol required for the examination of patients diagnosed with tumors and tumor-like neoplasms in a particular clinical case. Frontal and lateral views were used in the course of X-ray imaging. Histological studies included macroscopy and microscopy. RESULTS: According to the retrospective case record analysis made over the last 10 years 346 cases of facial bone osteoma were revealed and proved histologically comprising 3.7% of all benign osteogeneous maxillofacial tumors. For the first time in 10 years osteoma localized in the frontal bone had been revealed and thoroughly studied. Macroscopically - a semi-spherical and immovable neoformation 7 cm in diameter of hard consistency, splaying out at 4 cm and being adherent with the frontal bone. Roentgenologically - homogeneous intense shadowing of a round form with relatively distinct outlines complying with clinical sizes. According to the histological data, the tumor consists mostly of the solid osseous tissue and the spongy osseous tissue with the evident thickened trabeculas of the bone located in different directions. CONCLUSION: The analysis of historical data demonstrated extremely rare localization of primary osteoma of the frontal bone, and indicated the uniqueness of the case and significant clinical importance of its detailed study. PMID- 27685531 TI - Accessory spleen hypertrophy mimicking colon cancer metastasis. AB - Accessory spleen is a congenital form of an ectopic splenic tissue. In this report, we present a case of a patient who was followed with the diagnosis of rectal and sigmoid colon cancer and an accessory spleen hypertrophy, which was thought to be colon cancer metastasis in the left hypochondriac region. After colectomy and splenectomy, accessory spleen that mimics cancer metastasis was diffrentially diagnosed using scintigraphy. PMID- 27685533 TI - Yevhenii Petrovych Sidorik (1931-2016). AB - Professor Yevhenii Petrovych Sidorik, well-known scientist in the fields of biophysics and experimental oncology, double Laureate of the State Prize in Science and Technology, Laureate of O.O. Bohomolets Prize and R.E. Kavetsky Prize of the NAS of Ukraine died on the 86(th) year of his life. PMID- 27685535 TI - Influence of Computer-Generated Mosaic Photographs on Retinopathy of Prematurity Diagnosis and Management. AB - Importance: Telemedicine is becoming an increasingly important component of clinical care for retinopathy of prematurity (ROP), but little information exists regarding the role of mosaic photography for ROP telemedicine diagnosis. Objective: To examine the potential effect of computer-generated mosaic photographs on the diagnosis and management of ROP. Design, Setting, and Participants: In this prospective cohort study performed from July 12, 2011, through September 21, 2015, images were acquired from ROP screening at 8 academic institutions, and ROP experts interpreted 40 sets (20 sets with individual fundus photographs with >=3 fields and 20 computer-generated mosaic photographs) of wide angle retinal images from infants with ROP. All experts independently reviewed the 40 sets and provided a diagnosis and management plan for each set presented. Main Outcomes and Measures: The primary outcome measure was the sensitivity and specificity of the ROP diagnosis by experts that was calculated using a consensus reference standard diagnosis, determined from the diagnosis of fundus photographs by 3 experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. Mean unweighted kappa statistics were used to analyze the mean intergrader agreement among experts for diagnosis of zone, stage, plus disease, and category. Results: Nine ROP experts (4 women and 5 men) who have been practicing ophthalmology for a mean of 10.8 years (range, 3-24 years) consented to participate. Diagnosis by the mosaic photographs compared with diagnosis by multiple individual photographs resulted in improvements in sensitivity for diagnosis of stage 2 disease or worse (95.9% vs 88.9%; difference, 7.0; 95% CI, 3.5 to 10.5; P = .02), plus disease (85.7% vs 63.5%; difference, 22.2; 95% CI, 7.6 to 36.9; P = .02), and treatment-requiring ROP (84.4% vs 68.5%; difference, 15.9; 95% CI, 0.8 to 31.7; P = .047). With use of the kappa statistic, mosaic photographs, compared with multiple individual photographs, resulted in improvements in intergrader agreement for diagnosis of plus disease or not (0.54 vs 0.40; mean kappa difference, 0.14; 95% CI, 0.07 to 0.21; P = .004), stage 3 disease or worse or not (0.60 vs 0.52; mean kappa difference, 0.06; 95% CI, -0.06 to 0.18; P = .04), and type 2 ROP or not (0.58 vs 0.51; mean kappa difference, 0.07; 95% CI, 0.03 to 0.11; P = .04). After viewing the mosaic photographs, experts altered their choice of management in 42 of 180 responses (23.3%; 95% CI, 17.1%-29.5%). Conclusions and Relevance: Compared with multiple individual photographs, computer-generated mosaic photographs were associated with improved accuracy of image-based diagnosis for certain categories (eg, plus disease, stage 2 disease or worse, and treatment-requiring ROP) of ROP by experts. It is unclear, however, whether these findings are generalizable, and the results of this study may not be relevant to mosaic grading of other retinal vascular conditions. PMID- 27685536 TI - Biaxial Properties of the Left and Right Pulmonary Arteries in a Monocrotaline Rat Animal Model of Pulmonary Arterial Hypertension. AB - In a monocrotaline (MCT) induced-pulmonary arterial hypertension (PAH) rat animal model, the dynamic stress-strain relation was investigated in the circumferential and axial directions using a linear elastic response model within the quasi linear viscoelasticity theory framework. Right and left pulmonary arterial segments (RPA and LPA) were mechanically tested in a tubular biaxial device at the early stage (1 week post-MCT treatment) and at the advanced stage of the disease (4 weeks post-MCT treatment). The vessels were tested circumferentially at the in vivo axial length with matching in vivo measured pressure ranges. Subsequently, the vessels were tested axially at the mean pulmonary arterial pressure by stretching them from in vivo plus 5% of their length. Parameter estimation showed that the LPA and RPA remodel at different rates: axially, both vessels decreased in Young's modulus at the early stage of the disease, and increased at the advanced disease stage. Circumferentially, the Young's modulus increased in advanced PAH, but it was only significant in the RPA. The damping properties also changed in PAH; in the LPA relaxation times decreased continuously as the disease progressed, while in the RPA they initially increased and then decreased. Our modeling efforts were corroborated by the restructuring organization of the fibers imaged under multiphoton microscopy, where the collagen fibers become strongly aligned to the 45 deg angle in the RPA from an uncrimped and randomly organized state. Additionally, collagen content increased almost 10% in the RPA from the placebo to advanced PAH. PMID- 27685539 TI - Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors: a patent evaluation of US20160011199A1. AB - The present patent discloses the identification of small-molecule fluorescent probes constituted by pteroic acid moiety connected to near-infrared (NIR) dye via amino acids. These folate receptor (FR) targeted conjugates were shown to have high affinity for tumors that overexpress FRs. A selected compound from this new class, pteroyl-L-tyrosine-S0456 (OTL-0038), displays high affinity and specificity for FRs and was shown (i) to accumulate in vivo in tumor cells expressing FRs, and (ii) to be non-toxic in mice at clinical dose x 1000. This compound holds considerable promise for the location and detection of tumoral cells in the context of fluorescence guided surgery. PMID- 27685537 TI - Folded gastrulation and T48 drive the evolution of coordinated mesoderm internalization in flies. AB - Gastrulation constitutes a fundamental yet diverse morphogenetic process of metazoan development. Modes of gastrulation range from stochastic translocation of individual cells to coordinated infolding of an epithelial sheet. How such morphogenetic differences are genetically encoded and whether they have provided specific developmental advantages is unclear. Here we identify two genes, folded gastrulation and t48, which in the evolution of fly gastrulation acted as a likely switch from an ingression of individual cells to the invagination of the blastoderm epithelium. Both genes are expressed and required for mesoderm invagination in the fruit fly Drosophila melanogaster but do not appear during mesoderm ingression of the midge Chironomus riparius. We demonstrate that early expression of either or both of these genes in C.riparius is sufficient to invoke mesoderm invagination similar to D.melanogaster. The possible genetic simplicity and a measurable increase in developmental robustness might explain repeated evolution of similar transitions in animal gastrulation. PMID- 27685538 TI - Limited Benefit of the New Shorter Multidrug-Resistant Tuberculosis Regimen in Europe. PMID- 27685540 TI - Evolutionary Diversification of Prey and Predator Species Facilitated by Asymmetric Interactions. AB - We investigate the influence of asymmetric interactions on coevolutionary dynamics of a predator-prey system by using the theory of adaptive dynamics. We assume that the defense ability of prey and the attack ability of predators all can adaptively evolve, either caused by phenotypic plasticity or by behavioral choice, but there are certain costs in terms of their growth rate or death rate. The coevolutionary model is constructed from a deterministic approximation of random mutation-selection process. To sum up, if prey's trade-off curve is globally weakly concave, then five outcomes of coevolution are demonstrated, which depend on the intensity and shape of asymmetric predator-prey interactions and predator's trade-off shape. Firstly, we find that if there is a weakly decelerating cost and a weakly accelerating benefit for predator species, then evolutionary branching in the predator species may occur, but after branching further coevolution may lead to extinction of the predator species with a larger trait value. However, if there is a weakly accelerating cost and a weakly accelerating benefit for predator species, then evolutionary branching in the predator species is also possible and after branching the dimorphic predator can evolutionarily stably coexist with a monomorphic prey species. Secondly, if the asymmetric interactions become a little strong, then prey and predators will evolve to an evolutionarily stable equilibrium, at which they can stably coexist on a long-term timescale of evolution. Thirdly, if there is a weakly accelerating cost and a relatively strongly accelerating benefit for prey species, then evolutionary branching in the prey species is possible and the finally coevolutionary outcome contains a dimorphic prey and a monomorphic predator species. Fourthly, if the asymmetric interactions become more stronger, then predator-prey coevolution may lead to cycles in both traits and equilibrium population densities. The Red Queen dynamic is a possible outcome under asymmetric predator-prey interactions. PMID- 27685542 TI - Solid and liquid modernity: A comparison of the social geography of places to die in the UK and Australia. AB - Preferred place of care and death is a widely used quality measure for palliative and end of life care services. In this article we explore the use of Zygmunt Bauman's ideas on solid and liquid modernity to understand the complexity of the social geographical contexts of delivering and receiving care. Although solid ways of dying offer certainty and standardized care, more liquid ways allow for individualized care connected to family and communities. Understanding the complex tensions between solid and liquid aspects of palliative care may allow practitioners to help dying people to die in the ways and places they prefer. PMID- 27685543 TI - Expression and Purification of EPHA2 Tyrosine Kinase Domain for Crystallographic and NMR Studies. AB - The receptor tyrosine kinase EPHA2 is overexpressed in several cancers (breast, head and neck, non-small-cell lung cancer). Small-molecule-based inhibition of the EPHA2 kinase domain (KD) is seen as an important strategy for therapeutic intervention. However, obtaining structural information by crystallography or NMR spectroscopy for drug discovery is severely hampered by the lack of pure, homogeneous protein. Here, different fragments of the EPHA2 KD were expressed and purified from both bacterial (Escherichia coli, BL21(DE3) cells) and insect cells (Spodoptera frugiperda, Sf9 cells).1 H,15 N HSQC was used to determine the proper folding and homogeneity of all the constructs. Protein from E. coli was well folded but unstable, and it did not crystallize. However, a construct (D596-G900) produced in Sf9 cells yielded homogenous, well-folded protein that crystallized readily, thereby resulting in eleven new EPHA2-ligand crystal structures. We have also established a strategy for selective and uniform 15 N-amino acid labeling of EPHA2 KD in Sf9 cells for investigating dynamics and EPHA2-drug interactions by NMR. PMID- 27685546 TI - Proving nurses work. AB - Nearly everyone knows someone, a relative or friend who has been hit by unemployment and with three million people currently out of work it's hardly surprising. Nurses are no more immune from the recession than any other public sector staff. The days when a nursing qualification meant a job for life have long since past. The prospect of unemployment among nurses may have won public sympathy and a media outcry many years ago, now they are just another group of workers facing the inevitability of the dole queue. Or are they? PMID- 27685547 TI - Assessing a woundAccurate wound assessment is a prerequisite to planning appropriate nursing care and is essential to ensure the most appropriate choice of wound dressing products. However, this assessment is something practitioners often find difficult ( 1 ). AB - The aim of this Learning Unit is to develop your knowledge of wound assessment, and to increase your understanding of the rationale for effective planning, implementation and valuation of wound care. PMID- 27685541 TI - Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: what's memory got to do with it? AB - With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability. PMID- 27685544 TI - Synergistic mortality between a neonicotinoid insecticide and an ergosterol biosynthesis-inhibiting fungicide in three bee species. AB - BACKGROUND: Neonicotinoid insecticides have been identified as an important factor contributing to bee diversity declines. Nonetheless, uncertainties remain about their impact under field conditions. Most studies have been conducted on Apis mellifera and tested single compounds. However, in agricultural environments, bees are often exposed to multiple pesticides. We explore the synergistic mortality between a neonicotinoid (clothianidin) and an ergosterol biosynthesis-inhibiting fungicide (propiconazole) in three bee species (A. mellifera, Bombus terrestris, Osmia bicornis) following oral exposure in the laboratory. RESULTS: We developed a new approach based on the binomial proportion test to analyse synergistic interactions. We estimated uptake of clothianidin per foraging bout in honey bees foraging on seed-coated rapeseed fields. We found significant synergistic mortality in all three bee species exposed to non-lethal doses of propiconazole and their respective LD10 of clothianidin. Significant synergism was only found at the first assessment times in A. mellifera (4 and 24 h) and B. terrestris (4 h), but persisted throughout the experiment (96 h) in O. bicornis. O. bicornis was also the most sensitive species to clothianidin. CONCLUSION: Our results underscore the importance to test pesticide combinations likely to occur in agricultural environments, and to include several bee species in environmental risk assessment schemes. (c) 2016 Society of Chemical Industry. PMID- 27685548 TI - Pink pledge to work for a more open UK Council. AB - Whistleblowing nurse Graham Pink has pledged to work for a more open UKCC after his success in the first ever direct elections to Council. PMID- 27685545 TI - Towards N-Alkylimidazole Borane-based Hypergolic Fuels. AB - Over the past few decades, toxic and highly volatile hydrazine derivatives have been the main fuel choices for liquid bipropellants, especially in traditional hypergolic rocket engines. The search for new hypergolic fuels as replacements for hydrazine derivatives is of great interest to researchers. In this study, a series of N-alkylimidazole borane compounds has been synthesized and characterized. Interestingly, these compounds display promising applications as potential hypergolic fuels owing to their excellent physiochemical properties including low melting points, high thermal stability, low viscosities, and unique hypergolic reactivity. Compared with popular hypergolic ionic liquids, the cost effective and scaling-up advantages of these materials highlight their promising potential as high-performance fuels in liquid bipropellant formulations. PMID- 27685550 TI - New campaign highlights threats to patient services. AB - The RCN and Nursing Standard this week jointly launched a major national campaign to highlight the threats to patient services caused by cuts in nursing posts. It will also advise nurses facing redundancy. PMID- 27685552 TI - Nurse teacher jobs under threat? AB - Nurse teacher jobs could be threatened by North West Thames Regional Health Authority plans to offer a contract for pre-registration nurse training to the University of Hertfordshire. PMID- 27685549 TI - Bed closures at trust units. AB - A BBC Radio 4 survey has revealed that beds have closed at 60 per cent of Trust acute units because they had already completed their contracts. PMID- 27685553 TI - Pledge to fight reorganisation of Belfast health service. AB - Calls for a government inquiry and pledges to take the fight for the health service to the European Parliament were made at a meeting of the Eastern Health Board in Northern Ireland. PMID- 27685555 TI - Silenced by redundancy fears. AB - Redundancy-scared health professionals are afraid to speak out over the 'horrendous' levels of unemployment-related psychiatric illness currently blighting communities, psychiatrists warned last week. PMID- 27685554 TI - Trust's 'ageist' cuts could mean costly stays in hospital. AB - A health Trust's 'ageist' plans to axe 18 community nurses' health promotion posts will force elderly clients into needless and costly hospitalisation, the Royal College of Nursing has warned. PMID- 27685556 TI - Radical plans for nurse teachers. AB - Radical plans to shake up nurse teacher preparation have been welcomed by the RCN Council. The plans, drawn up by a College working group, recommend the phasing out of BEd degrees as suitable qualifying courses for nurse teachers. PMID- 27685557 TI - Emigration offers less opportunity. AB - Canada, once a magnet for British nurse emigrants, is now experiencing its own unemployment crisis, a Nova Scotian nurse has warned a London conference. PMID- 27685558 TI - Health service ignores what is known to work. AB - 'Apple pie' marketing statements like 'Meeting Customers' Needs' and 'Putting Quality Services First' have been ridiculed by Professor Alan Maynard, Director of the Centre for Health Economics at York University. PMID- 27685559 TI - Cash help for nurses should boost women managers. AB - Nurses who undertake Master's degrees with the aim of becoming senior NHS managers may get cash help from the government, Health Secretary Virginia Bottomley announced last week. PMID- 27685560 TI - Doubts about reformed health service. AB - Junior health minister Baroness Cumberlege admitted last week that not all doctors and nurses are convinced of the benefits of the reformed health service. PMID- 27685561 TI - Simple analgesics: choosing with care. AB - The aim of this Learning Unit is to develop your knowledge of 'over-the-counter' analgesics so that you can give informed advice to patients and clients. PMID- 27685563 TI - Overseas expertise could be lost. AB - The United Kingdom could lose the valuable expertise of overseas nurses under government plans to restrict immigration, according to the RCN. PMID- 27685562 TI - Funding plan could end two tier system. AB - Liberal Democrat Health and Community Care Spokesperson Liz Lynne is consulting nurses and other health professionals about a funding plan which she claims would end the two-tier system being created by the health reforms. PMID- 27685564 TI - Nurses are being gagged over reporting NHS faults. AB - Political blackmail, gags and penalties arc being used to stop nurses disclosing faults in the health service, parliament was told last week. PMID- 27685565 TI - ? AB - More financial assistance and support should be given to home carers. The Princess Royal argued when she gave the second annual lecture in aid of the Florence Nightingale Museum last week. Her Royal Highness, pictured arriving at St Thomas' Hospital, said society undervalues home care, and although it was possible to buy care, not everyone wants to or can afford it. PMID- 27685567 TI - Policy for NHS to help in foreign emergencies. AB - A national United Kingdom health policy to release National Health Service personnel for emergencies in developing countries should be a priority, says a new report. PMID- 27685566 TI - CGFNS applications invited. AB - Applications for the August 11 United States Commission on Graduates of Foreign Nursing Schools (CGFNS) exam must be completed and filed at the Philadelphia office by April 26. PMID- 27685568 TI - Needs of the terminally ill must be recognised. AB - The needs of people who are terminally ill must be urgently recognised and met if they are not to be disadvantaged by impending community care changes, say new guidelines published by the National Council for Hospice and Specialist Palliative Care Services. PMID- 27685569 TI - Midwifery training needs to be more balanced. AB - Midwifery training has become too academic and needs balancing by traditional apprenticeship methods, Professor Leslie Page, a member of the Department of Health's Expert Maternity Group, said last week. Intellectual and practical skills are 'not mutually exclusive', she told delegates at the English National Board's second annual national midwifery conference. PMID- 27685570 TI - UK breast cancer deaths highest in europe. AB - Infant mortality in the United Kingdom has dropped by a third since 1981, but breast cancer kills more women in the United Kingdom than in any other European county, the latest social trends figures from the Central Statistical Office show. PMID- 27685571 TI - URCC direct election results. AB - The following people have been electee! to the UK Central Council. They will take up their seats in April. PMID- 27685573 TI - Inappropriate dilatation and curettage in the NHS. AB - Dilatation and curettage (D&C), a diagnostic method used to treat women with menstrual problems, is often employed inappropriately and at large cost to the NHS, new research suggests. PMID- 27685574 TI - Primary health warning on stress in Asian women. AB - Primary health care teams must be alert in detecting psychological stress among Asian women, who are often reluctant to seek advice from mental health services, the Commission for Racial Equality warned last week. PMID- 27685575 TI - Partners of Parkinson sufferers 'share symptoms'. AB - Partners of people suffering from Parkinson's disease have been found to share some of the symptoms of the illness. PMID- 27685576 TI - Arrest rhythm indicator of survival after CPR. AB - The most important indicator for a successful outcome of cardiorespiratory resuscitation is the heart rhythm at the time of the arrest. PMID- 27685577 TI - Compliance poor in asthma treatment. AB - Health professionals must look at other ' means of improving patient compliance with treatment for asthma rather than relying on education in isolation. PMID- 27685578 TI - Mobile screening for diabetic retinopathy. AB - Mobile diabetic eye screening units might be particularly effective in identifying previously unrecognised retinopathy in rural areas. PMID- 27685579 TI - Right hand, right foot, right osteoarthritis? AB - Are you more likely to get osteoarthritis of the right hip if you are right dominant? Oxford researchers think this might be the case. PMID- 27685580 TI - Early osteopathy gives best results. AB - Suitable patients should be encouraged to see an osteopath early on in an illness episode, researchers suggest. PMID- 27685581 TI - Beating the stigma. AB - Mental health has again come under scrutiny recently, particularly the problems which can ensue when the community care net fails to hold. PMID- 27685582 TI - Tailor-made talk. AB - Patients whose first language is not English can present nursing staff with difficult communication problems. But in South Derbyshire help is at hand, as Charlotte Alderman reports. PMID- 27685583 TI - Leaving a legacy. AB - The Victorians used to boast that the sun never set on the British Empire. Now the Commonwealth Nurses Federation, with its membership of 53 National Nursing Associations spread right around the globe, can make a similar claim. PMID- 27685584 TI - An insecure future. AB - Nurses were incensed when Chancellor of the Exchequer Norman Lamont said in his Autumn statement that it was not unreasonable for public sector employees to accept a 1.5 per cent pay limit because they enjoyed job security. Not only are nurses angry about an imposed realterms reduction in their salaries; it is becoming increasingly clear that nurses no longer enjoy the kind of job security they have in the past. PMID- 27685585 TI - Chief nurses still loyal to nursing. AB - Gary Jones poses the question 'Have chief nurses abandoned nursing?' (Letters, January 13). No, chief nurses have not abandoned nursing. PMID- 27685587 TI - 'Tabloid press' view to nursing home care. AB - I would like to respond to Barbara Green's article 'A poor substitute for care' (Feature, January 20). PMID- 27685586 TI - A degree of disagreement. AB - In the news item 'Financial support for nurse teachers' (News, January 13), Stuart Mahon is reported as saying: 'If nursing is to be credible in the higher education sector, we have to have nurses who can lead nursing at that level, supported by a nursing degree.' PMID- 27685589 TI - Mental health act covers many issues. AB - May I thank David Maclsaac (Letters, January 20) for highlighting the point that a first-level RMN or RNMH is ; required to apply Section 5(4)of the Mental Health Act. PMID- 27685588 TI - Childminders can be connubial people too. AB - I have found a solution to child care which may be of interest to working mothers. PMID- 27685590 TI - ? AB - When are we going to see a balance in what is printed concerning elderly care? It seems that, as in the tabloid press, only the shocking and unacceptable receive mention. PMID- 27685592 TI - A popular and dedicated nurse. AB - A picture of Neil Bradshaw, senior staff nurse in our elderly care unit, appeared on the front cover of the January 6 issue of Nursing Standard. PMID- 27685591 TI - ? AB - * I was extremely concerned with Barbara Green's fictional account of life in a nursing home. There are few features on home care in the nursing press and many readers may feel that this feature offers an authoritative view. PMID- 27685593 TI - Information exchange. AB - * I am currently undertaking a staff nurse development course and have a project to complete based on what information is available for patients regarding sexual relationships after total hip arthroplasty. PMID- 27685594 TI - Pamela Hawthorn: a celebration. AB - Pam Hawthorn's cruel illness drew to a close a career of many achievements, and a rich vein of potential still to be explored. PMID- 27685595 TI - Go forth and multi-skill. AB - Hi there, health care workers. Remember I was telling you about multi-skilling as part of my new nursing model? PMID- 27685596 TI - Clinical Supervision and Mentorship in Nursing Clinical Supervision and Mentorship in Nursing T Butterworth and J Tangier Chapman & Hall 246pp L13.95 0 412-34910-8. AB - The United Kingdom Central Council's 'PREP' document emphasises the need for nurses to maintain and develop their standards of practice to meet the needs of patients and the health services. In Clinical Supervision and Mentorship in Nursing, Tony Butterworth and Jean Faugier have brought together various examples and models of clinical supervision which demonstrate ways in which standards of practice can be enhanced in line with the UKCC's aim. PMID- 27685597 TI - Dimensions of professional nursing, 6th edition Dimensions of professional nursing, 6th edition L Y Kelly Pergamon Press 748pp L21.95 0-08-040303-4. AB - For any nurse requiring insights and rationale for the impact of the US ethos of professional nursing upon that of the United Kingdom, they need look no further. PMID- 27685599 TI - Career listings. PMID- 27685598 TI - The ECG Made Easy The ECG Made Easy 4th edition J R Hampton Churchill Livingstone 106pp L4.50 0-443-04507-0. AB - The ECG Made Easy has, for some time, been the pocket reference for junior doctors. Its simple and easy to follow text has made it invaluable in the clinical setting. PMID- 27685601 TI - Evaluation of gender-specific aspects in quality-of-life in patients with larynx carcinoma. AB - CONCLUSIONS: The results suggest that gender-specific differences in health related quality-of-life (HRQoL) exist in patients with larynx carcinoma. In previous studies these differences might have been concealed by predominantly male subject groups. Future studies should consider a gender-specific analysis that suits the patient's idiosyncrasies associated with laryngeal cancer. OBJECTIVES: There is little research concerning gender differences in quality-of life (QoL) in patients with larynx carcinoma. Since laryngeal cancer is predominantly found in males, most studies examining HRQoL are based on a mainly male subject group. HRQoL needs to be assessed to determine the impact of disease and treatment and to evaluate possible treatment regimes. This study examined gender differences concerning HRQoL in 53 patients using EORTC QLQ-C30, and QLQ H&N35 questionnaires. METHODS: Patients treated with larynx carcinoma were given two questionnaires to assess HRQoL. The questionnaires were analyzed for each sex separately, as well as for the entire population. RESULTS: Female patients report significantly worse HRQoL than males. Age could not be identified as a significant predictor for HRQoL when males and females were analyzed together, and does not significantly predict HRQoL in men. However, age was found to be a significant predictor for HRQoL when only females were analyzed. PMID- 27685602 TI - Attitudes to lesbian, gay, bisexual and transgender parents seeking health care for their children in two early parenting services in Australia. AB - AIMS AND OBJECTIVES: To examine the attitudes to and knowledge and beliefs about homosexuality of nurses and allied professionals in two early parenting services in Australia. BACKGROUND: Early parenting services employ nurses and allied professionals. Access and inclusion policies are important in community health and early childhood service settings. However, little is known about the perceptions of professionals who work within early parenting services in relation to lesbian, gay, bisexual and transgender families. DESIGN: This is the final in a series of studies and was undertaken in two early parenting services in two states in Australia using a cross-sectional design with quantitative and qualitative approaches. METHODS: Validated questionnaires were completed by 51 nurses and allied professionals and tested with chi-squared test of independence (or Fisher's exact test), Mann-Whitney U-test, Kruskal-Wallis one-way analysis of variance or Spearman's rank correlation. Thematic analysis examined qualitative data collected in a box for free comments. RESULTS: Of the constructs measured by the questionnaires, no significant relationships were found in knowledge, attitude and gay affirmative practice scores by sociodemographic variables or professional group. However, attitude scores towards lesbians and gay men were significantly negatively affected by conservative political affiliation (p = 0.038), held religious beliefs (p = 0.011) and frequency of praying (p = 0.018). Six overall themes were found as follows: respect, parenting role, implications for the child, management, disclosure, resources and training. CONCLUSIONS: The study provided an in-depth analysis of the attitudes, knowledge and beliefs of professionals in two early parenting services, showing that work is needed to promote acceptance of diversity and the inclusion of lesbian, gay, bisexual and transgender families in planning, developing, evaluating and accessing early parenting services. RELEVANCE TO CLINICAL PRACTICE: Access and inclusion plans for lesbian, gay, bisexual and transgender families are crucial in early parenting services in Australia and should be included in professional development programmes. PMID- 27685603 TI - Periodontitis as a Modifiable Risk Factor for Dementia: A Nationwide Population Based Cohort Study. AB - OBJECTIVES: To determine whether periodontitis is a modifiable risk factor for dementia. DESIGN: Prospective cohort study. SETTING: National Health Insurance Research Database in Taiwan. PARTICIPANTS: Individuals aged 65 and older with periodontitis (n = 3,028) and an age- and sex-matched control group (n = 3,028). MEASUREMENTS: Individuals with periodontitis were compared age- and sex-matched controls with for incidence density and hazard ratio (HR) of new-onset dementia. Periodontitis was defined according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 diagnosed by dentists. To ensure diagnostic validity, only those who had concurrently received antibiotic therapies, periodontal treatment other than scaling, or scaling more than twice per year performed by certified dentists were included. Dementia was defined according to ICD-9-CM codes 290.0-290.4, 294.1, 331.0-331.2. RESULTS: After adjustment for confounding factors, the risk of developing dementia was calculated to be higher for participants with periodontitis (HR = 1.16, 95% confidence interval = 1.01-1.32, P = .03) than for those without. CONCLUSION: Periodontitis is associated with greater risk of developing dementia. Periodontal infection is treatable, so it might be a modifiable risk factor for dementia. Clinicians must devote greater attention to this potential association in an effort to develop new preventive and therapeutic strategies for dementia. PMID- 27685604 TI - Analogy motor learning by young children: a study of rope skipping. AB - Research in psychology suggests that provision of an instruction by analogy can enhance acquisition and understanding of knowledge. Limited research has been conducted to test this proposition in motor learning by children. The purpose of the present study was to examine the feasibility of analogy instructions in motor skill acquisition by children. Thirty-two children were randomly assigned to one of the two instruction protocols: analogy and explicit instruction protocols for a two-week rope skipping training. Each participant completed a pretest (Lesson 1), three practice sessions (Lesson 2-4), a posttest and a secondary task test (Lesson 5). Children in the analogy protocol displayed better rope skip performance than those in the explicit instruction protocol (p < .001). Moreover, a cognitive secondary task test indicated that children in the analogy protocol performed more effectively, whereas children in the explicit protocol displayed decrements in performance. Analogy learning may aid children to acquire complex motor skills, and have potential benefits related to reduced cognitive processing requirements. PMID- 27685605 TI - Transglutaminase 2 strongly binds to an extracellular matrix component other than fibronectin via its second C-terminal beta-barrel domain. AB - Transglutaminase 2 (TG2) is a ubiquitous crosslinking enzyme present in both intra- and extracellular in many cell types and tissues. TG2 is upregulated upon cellular stress or injury, and extracellular TG2 is implicated in several human diseases, including celiac disease. However, incomplete knowledge about extracellular TG2 biology limits our understanding of how TG2 is involved in disease. Here, we demonstrate that binding of TG2 to the ECM of small intestinal tissue sections is the sum of binding to fibronectin (FN) via its N-terminal domain and binding to an abundant, novel extracellular matrix (ECM) interaction partner via its second C-terminal beta-barrel domain. The latter interaction dominates and gives rise to the characteristic reticular staining pattern of extracellular TG2. Of relevance for celiac disease, we show that self multimerized TG2 does not efficiently deposit in the intestinal ECM, and TG2 complexes may thus become free-floating antigens in tissues in contrast to monomeric TG2 that would readily become sequestered by the ECM. Upon injection of monoclonal antibody targeting the FN-binding site, we observe antibody deposition on extracellular TG2 in cryosections, suggesting that the FN-binding site of TG2 is exposed in vivo. This would explain how and why celiac autoantibodies recognizing the FN-binding site of TG2 can bind TG2 in vitro, in situ as well as in vivo. PMID- 27685606 TI - Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics. AB - BACKGROUND: Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics. METHODS: Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study. Blood was collected before and 24 h after the challenge. The surface expression of IL-25R was evaluated by flow cytometry on eosinophils and Th2 memory cells. In addition, plasma levels of IL-25 were measured by ELISA, and functional responses to IL-25 including type 2 cytokine expression, degranulation, and the migrational responsiveness of eosinophils were evaluated in vitro. RESULTS: Following the allergen but not the diluent inhalation challenge, significant increases in the expression of IL-17RB and IL 17RA/B were found on eosinophils but not on Th2 memory cells. IL-25 plasma levels and the number of eosinophils but not of Th2 memory cells expressing intracellular IL-25 increased significantly in response to the allergen but not the diluent challenge. Stimulation with physiologically relevant concentrations of IL-25 in vitro caused (i) degranulation of eosinophils (measured by eosinophil peroxidase release), (ii) enhanced intracellular expression of IL-5 and IL-13, and (iii) priming of eosinophil migration to eotaxin. IL-25 stimulated intracellular cytokine expression, and the migration of eosinophils was blocked in the presence of a neutralizing IL-25 antibody. CONCLUSIONS: Our findings suggest that the IL-25/IL-25R axis may play an important role in promoting the recruitment and proinflammatory function of eosinophils in allergic asthma. PMID- 27685607 TI - Integrative analysis of Arabidopsis thaliana transcriptomics reveals intuitive splicing mechanism for circular RNA. AB - A new regulatory class of small endogenous RNAs called circular RNAs (circRNAs) has been described as miRNA sponges in animals. Using 16 Arabidopsis thaliana RNA Seq data sets, we identified 803 circRNAs in RNase R-/non-RNase R-treated samples. The results revealed the following features: Canonical and noncanonical splicing can generate circRNAs; chloroplasts are a hotspot for circRNA generation; furthermore, limited complementary sequences exist not only in introns, but also in the sequences flanking splice sites. The latter finding suggests that multiple combinations between complementary sequences may facilitate the formation of the circular structure. Our results contribute to a better understanding of this novel class of plant circRNAs. PMID- 27685608 TI - Omalizumab in patient with aspirin exacerbated respiratory disease and chronic idiopathic urticaria. AB - Aspirin hypersensitivity associated with chronic rhinosinusitis-with or without nasal polyposis-and asthma resistant to conventional therapy defines the aspirin exacerbated respiratory disease (AERD). We describe the case of a 15-year-old female patient with adverse reaction to aspirin, chronic rhinosinusitis, and severe asthma. She also experienced chronic idiopathic urticaria worsened by non steroidal anti-inflammatory drug administration. AERD was diagnosed based on clinical history and symptoms. Given the poor responsiveness to standard therapy for respiratory and cutaneous symptoms, omalizumab was administered for 24 weeks with control of respiratory symptoms and short term improvement of cutaneous symptoms. Pediatr Pulmonol. 2017;52:E26-E28. (c) 2016 Wiley Periodicals, Inc. PMID- 27685609 TI - A randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services: the Northern Ireland Caries Prevention In Practice (NIC-PIP) trial. AB - BACKGROUND: Dental caries is the most common disease of childhood. The NHS guidelines promote preventative care in dental practices, particularly for young children. However, the cost-effectiveness of this policy has not been established. OBJECTIVE: To measure the effects and costs of a composite fluoride intervention designed to prevent caries in young children attending dental services. DESIGN: The study was a two-arm, parallel-group, randomised controlled trial, with an allocation ratio of 1 : 1. Randomisation was by clinical trials unit, using randomised permuted blocks. Children/families were not blinded; however, outcome assessment was blinded to group assessment. SETTING: The study took place in 22 NHS dental practices in Northern Ireland, UK. PARTICIPANTS: The study participants were children aged 2-3 years, who were caries free at baseline. INTERVENTIONS: The intervention was composite in nature, comprising a varnish containing 22,600 parts per million (p.p.m.) fluoride, a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m. fluoride; plus standardised, evidence-based prevention advice provided at 6-monthly intervals over 3 years. The control group received the prevention advice alone. MAIN OUTCOME MEASURES: The primary outcome measure was conversion from caries-free to caries-active states. Secondary outcome measures were the number of decayed, missing or filled tooth surfaces in primary dentition (dmfs) in caries-active children, the number of episodes of pain, the number of extracted teeth and the costs of care. Adverse reactions (ARs) were recorded. RESULTS: A total of 1248 children (624 randomised to each group) were recruited and 1096 (549 in the intervention group and 547 in the control group) were included in the final analyses. A total of 87% of the intervention children and 85% of control children attended every 6-month visit (p = 0.77). In total, 187 (34%) children in the intervention group converted to caries active, compared with 213 (39%) in the control group [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.64 to 1.04; p = 0.11]. The mean number of tooth surfaces affected by caries was 7.2 in the intervention group, compared with 9.6 in the control group (p = 0.007). There was no significant difference in the number of episodes of pain between groups (p = 0.81). However, 164 out of the total of 400 (41%) children who converted to caries active reported toothache, compared with 62 out of 696 (9%) caries-free children (OR 7.1 95% CI 5.1 to 9.9; p < 0.001). There was no statistically significant difference in the number of teeth extracted in caries-active children (p = 0.95). Ten children in the intervention group had ARs of a minor nature. The average direct dental care cost was L155.74 for the intervention group and L48.21 for the control group over 3 years (p < 0.05). The mean cost per carious surface avoided over the 3 years was estimated at L251.00. LIMITATIONS: The usual limitations of a trial such as generalisability and understanding the underlying reasons for the outcomes apply. There is no mean willingness-to-pay threshold available to enable assessment of value for money. CONCLUSIONS: A statistically significant effect could not be demonstrated for the primary outcome. Once caries develop, pain is likely. There was a statistically significant difference in dmfs in caries-active children in favour of the intervention. Although adequately powered, the effect size of the intervention was small and of questionable clinical and economic benefit. FUTURE WORK: Future work should assess the caries prevention effects of interventions to reduce sugar consumption at the population and individual levels. Interventions designed to arrest the disease once it is established need to be developed and tested in practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36180119 and EudraCT 2009-010725-39. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 71. See the NIHR Journals Library website for further project information. PMID- 27685610 TI - Removal of Pertechnetate-Related Oxyanions from Solution Using Functionalized Hierarchical Porous Frameworks. AB - Efficient and cost-effective removal of radioactive pertechnetate anions from nuclear waste is a key challenge to mitigate long-term nuclear waste storage issues. Traditional materials such as resins and layered double hydroxides (LDHs) were evaluated for their pertechnetate or perrhenate (the non-radioactive surrogate) removal capacity, but there is room for improvement in terms of capacity, selectivity and kinetics. A series of functionalized hierarchical porous frameworks were evaluated for their perrhenate removal capacity in the presence of other competing anions. PMID- 27685611 TI - Efficacy of Teaching the Gambee Suture Pattern Using Simulated Small Intestine versus Cadaveric Small Intestine. AB - OBJECTIVE: To determine if instruction using simulated small intestine (SSI) is as effective as using cadaveric small intestine to teach the Gambee suture pattern to second year veterinary students. STUDY DESIGN: Prospective, randomized, blinded study. SAMPLE POPULATION: Second year veterinary students (n=59). METHODS: Students were randomly assigned to groups using SSI or equine cadaver small intestine (CSI) to learn the Gambee suture pattern. The same educator, an experienced surgical instructor, instructed all students. Instruction consisted of verbal description of the technique with a schematic diagram followed by a demonstration. Students then practiced the technique with supervision and verbal feedback. One week later, 3 board certified surgeons experienced in surgical instruction evaluated each student suturing equine CSI and scored them using a rubric developed and validated for surgical skills assessment. RESULTS: Fifty-nine students were enrolled (4 students were absent for the lab during which the assessment was performed; 55 students were available for evaluation). Of the 55 students evaluated, 26 were in the SSI group and 29 were in the CSI group. There was no significant difference between CSI and SSI groups in ability to perform the Gambee suture pattern using equine CSI 1 week following training. CONCLUSION: SSI is as effective as equine cadaveric small intestine tissue to teach the Gambee suture pattern to second year veterinary students. If cadaver tissue is unavailable or undesirable, SSI could be used to instruct suture placement techniques. PMID- 27685615 TI - Lamb-dip spectroscopy of the C-N stretching band of methylamine by using frequency-tunable microwave sidebands of CO2 laser lines. AB - Lamb-dip spectroscopy of the C-N stretching band of methylamine has been systematically extended to P-, Q-, and R-branch by using microwave sidebands of a large number of CO2 laser lines as frequency-tunable infrared sources in a sub Doppler spectrometer. Lamb-dip signals of more than 150 spectral lines have been observed with a resolution of 0.4 MHz and their frequencies have been precisely measured with an accuracy of +/-0.1 MHz. More than 30 closed combination loops have been formed, which unambiguously confirm the assignments. For over 150 vibrational excited levels in 27 substates, refined term values have been determined and expanded in J(J + 1) power-series to determine the substate origins and the effective rotational constants. For transitions with Aa torsion inversion symmetry in torsional state upsilont = 0, 57 K-doublet lines displaying asymmetry splittings have been observed and the splitting constants for levels with K = 1, 2, and 3 in the excited states have been determined. Our results provide accurate experimental information for spectroscopic studies of the interesting vibrational perturbations and intermode interactions related to the C N stretching mode, directly support astronomical surveys, and are very relevant in practice to identification and frequency determination of the CO2-laser-pumped far-infrared laser lines of methylamine. PMID- 27685614 TI - siRNA Transfection and EMSA Analyses on Freshly Isolated Human Villous Cytotrophoblasts. AB - Human primary villous cytotrophoblasts are a very useful source of primary cells to study placental functions and regulatory mechanisms, and to comprehend diseases related to pregnancy. In this protocol, human primary villous cytotrophoblasts freshly isolated from placentas through a standard DNase/trypsin protocol are microporated with small interfering RNA (siRNA). This approach provided greater efficiency for siRNA transfection when compared to a lipofection based method. Transfected cells can subsequently be analyzed by standard Western blot within a time frame of 3-4 days post-transfection. In addition, using cultured primary villous cytotrophoblasts, Electrophoretic Mobility Shift Assay (EMSA) analysis was optimized and performed on extracts from days 1 to 4. The use of these cultured primary cells and the protocol described allow for an evaluation of the implication of specific genes and transcription factors in the process of villous cytotrophoblast differentiation into a syncytiotrophoblast like cell layer. However, the limited time span allowable in culture precludes the use of methods requiring more time, such as generation of a stable cell population. Therefore testing of this cell population requires highly optimized gene transfer protocols. PMID- 27685613 TI - [Malnutrition in Elderly Trauma Patients - Comparison of Two Assessment Tools]. AB - Background: The prevalence of malnutrition in hospitalised patients is reported to be between 16 and 55 % across disciplines. Within hospital care, screening for malnutrition is required. However, in orthopaedics and trauma surgery, there is still no generally accepted recommendation for the methods for such a data survey. In the present study, the following aspects are to be investigated with the help of two established scores: (1) the prevalence of malnutrition in the patient population of geriatric trauma care, and (2) the correlation between methods of data survey. Material and Methods: Between June 2014 and June 2015, a consecutive series of hospitalised trauma patients were studied prospectively with two validated screening instruments to record nutritional status. The study was carried out at a municipal trauma surgery hospital, which is a first level interregional trauma centre as well as a university hospital. The Nutritional Risk Screening (NRS) and the Mini Nutritional Assessment (MNA Short and Long Form) were used. All patients were divided into three age groups: < 65 years, 65 80 years, and > 80 years. The prevalence of malnutrition in geriatric trauma patients and the correlation between the screening instruments were determined. For a better comparison, prescreening and main assessment were applied to all patients. For statistical evaluation, both quantitative and semi-quantitative parameters were used. Furthermore, the Kolmogorov-Smirnov test, Spearman's correlation analysis and the chi-square test were applied. These tests were two sided and had a level of significance of 5 %. The present study was partially funded by the Oskar-Helene-Heim Foundation. Results: 521 patients (43.8 % women, 56.2 % men), with a mean age of 53.96 +/- 18.13 years, were statistically evaluated within the present study. Depending on the method of the data survey, malnutrition (NRS>=3) in geriatric trauma patients varied from 31.3 % (65-80 years) to 60 % (> 80 years). With MNA, 28.8 and 54.3 % of patients were at risk of malnutrition (MNA 17-23.5), while the fractions of patients already suffering from malnutrition (MNA < 17) were 5.4 and 8.6 %, respectively. The correlation between the NRS and MNA total scores increases with the age of the patients. The correlation coefficient for patients under 65 years is r = - 0.380, while among patients aged between 65 and 80, it is r = - 0.481, and for patients over 80 years, there is a medium to strong correlation of r = - 0.638 (each with a Spearman correlation of p < 0.001). For the total population as well as the different age groups, statistically significant correlations were recorded between the categorised scores (chi-square test for linear trend, p < 0.001). Summary: The present study demonstrates high prevalence of malnutrition among the geriatric trauma patients. Because of its easy and rapid application, the NRS has an advantage in clinical use. It was shown that the two methods of data survey were highly correlated. PMID- 27685612 TI - Phase I trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine. AB - GBS-01, an extract from the fruit of Arctium lappa L. is an orally administered drug rich in arctigenin, which has been reported to exert antitumor activity by attenuating the tolerance of cancer cells to glucose deprivation. We investigated the maximum tolerated dose of GBS-01 based on the frequency of the dose-limiting toxicities (DLTs) and pharmacokinetics in patients with advanced pancreatic cancer refractory to gemcitabine. GBS-01 was given orally at escalating doses from 3.0 g (containing 1.0 g burdock fruit extract) to 12.0 g q.d. A DLT was defined as a grade 4 hematological toxicity and grade 3 or 4 non-hematological toxicity appearing during the first 28 days of treatment. Fifteen patients (GBS 01 dose level 1 [3.0 g], three patients; dose level 2 [7.5 g], three patients; and dose level 3 [12.0 g], nine patients) were enrolled. None of the patients at any of the three dose levels showed any sign of DLTs. The main adverse events were increased serum gamma-glutamyl transpeptidase, hyperglycemia, and increased serum total bilirubin; however, all the toxicities were mild. Of the 15 patients, 1 showed confirmed partial response and 4 patients had stable disease. The median progression-free and overall survival of the patients were 1.1 and 5.7 months, respectively. The pharmacokinetic study revealed a high bioavailability of arctigenin and rapid conjugation of the drug with glucuronic acid. The recommended dose of GBS-01 was 12.0 g q.d, and favorable clinical responses were obtained. This trial was registered at UMIN-CTR (http://www.umin.ac.jp/ctr/index j.htm), identification number UMIN000005787. PMID- 27685622 TI - Posttranslational arginylation enzyme Ate1 affects DNA mutagenesis by regulating stress response. AB - Arginyltransferase 1 (Ate1) mediates protein arginylation, a poorly understood protein posttranslational modification (PTM) in eukaryotic cells. Previous evidence suggest a potential involvement of arginylation in stress response and this PTM was traditionally considered anti-apoptotic based on the studies of individual substrates. However, here we found that arginylation promotes cell death and/or growth arrest, depending on the nature and intensity of the stressing factor. Specifically, in yeast, mouse and human cells, deletion or downregulation of the ATE1 gene disrupts typical stress responses by bypassing growth arrest and suppressing cell death events in the presence of disease related stressing factors, including oxidative, heat, and osmotic stresses, as well as the exposure to heavy metals or radiation. Conversely, in wild-type cells responding to stress, there is an increase of cellular Ate1 protein level and arginylation activity. Furthermore, the increase of Ate1 protein directly promotes cell death in a manner dependent on its arginylation activity. Finally, we found Ate1 to be required to suppress mutation frequency in yeast and mammalian cells during DNA-damaging conditions such as ultraviolet irradiation. Our study clarifies the role of Ate1/arginylation in stress response and provides a new mechanism to explain the link between Ate1 and a variety of diseases including cancer. This is also the first example that the modulation of the global level of a PTM is capable of affecting DNA mutagenesis. PMID- 27685621 TI - miR-612 suppresses stem cell-like property of hepatocellular carcinoma cells by modulating Sp1/Nanog signaling. AB - In our previous study we found that miR-612 negatively regulated stem cell-like property and tumor metastasis of hepatocellular carcinoma cells (HCC). In this study, we try to elucidate underlying mechanism of the regulation, and find that miR-612 inversely modulate the mRNA and protein level of epithelial cell adhesion molecule as well as CD133, negatively regulate the numbers and sizes of tumor spheres, directly inhibit the protein level of Sp1, and subsequently reduce transcription activity of Nanog. Of importance, the higher levels of Sp1 and Nanog in biopsies are the more unfavorable prognoses of HCC patients are found after tumor resection. Taken together, miR-612 has a suppressive role on HCC stemness via Sp1/Nanog signaling pathway. PMID- 27685624 TI - Short-term EGFR blockade enhances immune-mediated cytotoxicity of EGFR mutant lung cancer cells: rationale for combination therapies. AB - The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib has been approved for years as a first-line therapy for patients harboring EGFR-sensitizing mutations. With the promising implementation of immunotherapeutic strategies for the treatment of lung cancer, there is a growing interest in developing combinatorial therapies that could utilize immune approaches in the context of conventional or targeted therapies. Tumor cells are known to evade immune attack by multiple strategies, including undergoing phenotypic plasticity via a process designated as the epithelial-mesenchymal transition (EMT). As signaling through EGFR is a major inducer of EMT in epithelial cells, we have investigated the effect of EGFR inhibition with erlotinib on tumor phenotype and susceptibility to immune attack. Our data shows that short-term exposure of tumor cells to low-dose erlotinib modulates tumor plasticity and immune-mediated cytotoxicity in lung cancer cells harboring a sensitizing EGFR mutation, leading to a remarkable enhancement of tumor lysis mediated by innate NK cells and antigen-specific T cells. This effect positively correlated with the ability of short-term EGFR blockade to modulate tumor phenotype towards a more epithelial one, as well as to increase susceptibility to caspase-mediated apoptosis. The effect, however, was lost when erlotinib was utilized for long periods of time in vitro or in vivo, which resulted in gain of mesenchymal features and decreased (rather than increased) tumor lysis in response to immune effector mechanisms. Our data provides rationale for potential combinations of erlotinib and immunotherapies for the treatment of lung carcinomas in the early setting, before the establishment of tumor relapse with long-term EGFR inhibition. PMID- 27685623 TI - Kinase-independent function of RIP1, critical for mature T-cell survival and proliferation. AB - The death receptor, Fas, triggers apoptotic death and is essential for maintaining homeostasis in the peripheral lymphoid organs. RIP1 was originally cloned when searching for Fas-binding proteins and was later shown to associate also with the signaling complex of TNFR1. Although Fas exclusively induces apoptosis, TNFR1 primarily activates the pro-survival/pro-inflammatory NF-kappaB pathway. Mutations in Fas lead to lymphoproliferative (lpr) diseases, and deletion of TNFR1 results in defective innate immune responses. However, the function of RIP1 in the adult lymphoid system has not been well understood, primarily owing to perinatal lethality in mice lacking the entire RIP1 protein in germ cells. This current study investigated the requirement for RIP1 in the T lineage using viable RIP1 mutant mice containing a conditional and kinase-dead RIP1 allele. Disabling the kinase activity of RIP1 had no obvious impact on the T cell compartment. However, T-cell-specific deletion of RIP1 led to a severe T lymphopenic condition, owing to a dramatically reduced mature T-cell pool in the periphery. Interestingly, the immature T-cell compartment in the thymus appeared intact. Further analysis showed that mature RIP1-/- T cells were severely defective in antigen receptor-induced proliferative responses. Moreover, the RIP1 /- T cells displayed greatly increased death and contained elevated caspase activities, an indication of apoptosis. In total, these results revealed a novel, kinase-independent function of RIP1, which is essential for not only promoting TCR-induced proliferative responses but also in blocking apoptosis in mature T cells. PMID- 27685625 TI - TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints. AB - Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFbeta-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, although the underlying molecular regulatory mechanisms are not well defined. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8-mediated apoptotic signaling through both NFkappaB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFalpha-induced cell death through the induction of RIP1 phosphorylation/activation and necrosome formation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role for the adaptor protein TNF receptor-associated protein with death domain (TRADD) in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key pro-survival signaling proteins and necrosome formation. Thus, we identified new regulatory mechanisms underlying the critical role of TAK1 in cell survival through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis. PMID- 27685626 TI - miRNA-558 promotes gastric cancer progression through attenuating Smad4-mediated repression of heparanase expression. AB - Previous studies have indicated that as the only mammalian endo-beta-D glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines. In contrast, Smad4 suppressed the nascent transcription and expression of HPSE via directly binding to its promoter. Mechanistically, miR-558 recognized its complementary site within HPSE promoter to decrease the binding of Smad4 in an Argonaute 1-dependent manner. Ectopic expression or knockdown experiments indicated that miR-558 promoted the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cell lines via attenuating Smad4-mediated repression of HPSE expression. In clinical gastric cancer specimens, up regulation of miR-558 and down-regulation of Smad4 were positively correlated with HPSE expression. Kaplan-Meier survival analysis revealed that miR-558 and Smad4 were associated with unfavourable and favourable outcome of gastric cancer patients, respectively. Therefore, these findings demonstrate that miR-558 facilitates the progression of gastric cancer through directly targeting the HPSE promoter to attenuate Smad4-mediated repression of HPSE expression. PMID- 27685629 TI - Bivalent IAP antagonists inhibit TRAF2-bound cIAPs and limit TNF-mediated NF kappaB signaling. PMID- 27685627 TI - CHK1 and RAD51 activation after DNA damage is regulated via urokinase receptor/TLR4 signaling. AB - Mechanisms of DNA damage and repair signaling are not completely understood that hinder the efficiency of cancer therapy. Urokinase-type plasminogen activator receptor (PLAUR) is highly expressed in most solid cancers and serves as a marker of poor prognosis. We show that PLAUR actively promotes DNA repair in cancer cells. On the contrary, downregulation of PLAUR expression results in delayed DNA repair. We found PLAUR to be essential for activation of Checkpoint kinase 1 (CHK1); maintenance of cell cycle arrest after DNA damage in a TP53-dependent manner; expression, nuclear import and recruitment to DNA-damage foci of RAD51 recombinase, the principal protein involved in the homologous recombination repair pathway. Underlying mechanism implies auto-/paracrine signaling of PLAUR/TLR4 receptor complex leading to activation of CHK1 and DNA repair. The signaling is induced by a danger molecule released by DNA-damaged cells and mediates, at least partially, activation of DNA-damage response. This study describes a new mechanism of DNA repair activation initiated by auto-/paracrine signaling of membrane receptors PLAUR/TLR4. It adds to the understanding of role of PLAUR in cancer and provides a rationale for therapeutic targeting of PLAUR/TLR4 interaction in TP53-positive cancers. PMID- 27685628 TI - The Fra-1-miR-134-SDS22 feedback loop amplifies ERK/JNK signaling and reduces chemosensitivity in ovarian cancer cells. AB - The Fra-1 transcription factor is frequently upregulated in multiple types of tumors. Here we found that Fra-1 promotes miR-134 expression. miR-134 activates JNK and ERK by targeting SDS22, which in turn induces Fra-1 expression and leads to miR-134 upregulation. In addition, miR-134 augmented H2AX S139 phosphorylation by activating JNK and promoted non-homologous end joining (NHEJ)-mediated DNA repair. Therefore, ectopic miR-134 expression reduced chemosensitivity in ovarian cancer cells. Furthermore, miR-134 promotes cell proliferation, migration and invasion of ovarian cancer cells, and enhances tumor growth in vivo. Of particular significance, both Fra-1 and miR-134 are upregulated in ovarian cancer tissues, and Fra-1 and miR-134 expression is positively correlated. High levels of miR-134 expression were associated with a reduced median survival of ovarian cancer patients. Our study revealed that a Fra-1-miR-134 axis drives a positive feedback loop that amplifies ERK/JNK signaling and reduces chemosensitivity in ovarian cancer cells. PMID- 27685631 TI - Mesenchymal stem cells stimulate intestinal stem cells to repair radiation induced intestinal injury. AB - The loss of stem cells residing in the base of the intestinal crypt has a key role in radiation-induced intestinal injury. In particular, Lgr5+ intestinal stem cells (ISCs) are indispensable for intestinal regeneration following exposure to radiation. Mesenchymal stem cells (MSCs) have previously been shown to improve intestinal epithelial repair in a mouse model of radiation injury, and, therefore, it was hypothesized that this protective effect is related to Lgr5+ ISCs. In this study, it was found that, following exposure to radiation, transplantation of MSCs improved the survival of the mice, ameliorated intestinal injury and increased the number of regenerating crypts. Furthermore, there was a significant increase in Lgr5+ ISCs and their daughter cells, including Ki67+ transient amplifying cells, Vil1+ enterocytes and lysozyme+ Paneth cells, in response to treatment with MSCs. Crypts isolated from mice treated with MSCs formed a higher number of and larger enteroids than those from the PBS group. MSC transplantation also reduced the number of apoptotic cells within the small intestine at 6 h post-radiation. Interestingly, Wnt3a and active beta-catenin protein levels were increased in the small intestines of MSC-treated mice. In addition, intravenous delivery of recombinant mouse Wnt3a after radiation reduced damage in the small intestine and was radioprotective, although not to the same degree as MSC treatment. Our results show that MSCs support the growth of endogenous Lgr5+ ISCs, thus promoting repair of the small intestine following exposure to radiation. The molecular mechanism of action mediating this was found to be related to increased activation of the Wnt/beta-catenin signaling pathway. PMID- 27685630 TI - Pharmacologic inhibition of reactive gliosis blocks TNF-alpha-mediated neuronal apoptosis. AB - Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo. The mammalian retina is an accessible model to study the regulation of astrocyte stress responses, and their influence on retinal neuronal homeostasis. In particular, our work and others have implicated p38 mitogen-activated protein kinase (MAPK) signaling as a key regulator of glutamate recycling, antioxidant activity and cytokine secretion by astrocytes and related Muller glia, with potent influences on neighboring neurons. Here we report experiments with the small molecule inhibitor, withaferin A (WFA), to specifically block type III IF dynamics in vivo. WFA was administered in a model of metabolic retinal injury induced by kainic acid, and in combination with a recent model of debridement induced astrocyte reactivity. We show that WFA specifically targets IFs and reduces astrocyte and Muller glial reactivity in vivo. Inhibition of glial IF polymerization blocked p38 MAPK-dependent secretion of TNF-alpha, resulting in markedly reduced neuronal apoptosis. To our knowledge this is the first study to demonstrate that pharmacologic inhibition of IF dynamics in reactive glia protects neurons in vivo. PMID- 27685632 TI - Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma. AB - Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR 623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy. PMID- 27685634 TI - Activation of necroptosis in human and experimental cholestasis. AB - Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3-/-) mice subjected to common bile duct ligation (BDL). The functional link between RIP3, heme oxygenase-1 (HO-1) and antioxidant response was investigated in vivo after BDL and in vitro. We demonstrate increased RIP3 expression and mixed lineage kinase domain-like protein (MLKL) phosphorylation in liver samples of human PBC patients, coincident with thioflavin T labeling, suggesting activation of necroptosis. BDL resulted in evident hallmarks of necroptosis, concomitant with progressive bile duct hyperplasia, multifocal necrosis, fibrosis and inflammation. MLKL phosphorylation was increased and insoluble aggregates of RIP3, MLKL and RIP1 formed in BLD liver tissue samples. Furthermore, RIP3 deficiency blocked BDL-induced necroinflammation at 3 and 14 days post-BDL. Serum hepatic enzymes, fibrogenic liver gene expression and oxidative stress decreased in RIP3-/- mice at 3 days after BDL. However, at 14 days, cholestasis aggravated and fibrosis was not halted. RIP3 deficiency further associated with increased hepatic expression of HO-1 and accumulation of iron in BDL mice. The functional link between HO-1 activity and bile acid toxicity was established in RIP3 deficient primary hepatocytes. Necroptosis is triggered in PBC patients and mediates hepatic necroinflammation in BDL-induced acute cholestasis. Targeting necroptosis may represent a therapeutic strategy for acute cholestasis, although complementary approaches may be required to control progression of chronic cholestatic liver disease. PMID- 27685636 TI - JAK polymorphisms: jack of all cytokines, masters GVHD? PMID- 27685633 TI - Long noncoding RNAs in the progression, metastasis, and prognosis of osteosarcoma. AB - Long noncoding RNAs (lncRNAs) are a class of non-protein-coding molecules longer than 200 nucleotides that are involved in the development and progression of many types of tumors. Numerous lncRNAs regulate cell proliferation, metastasis, and chemotherapeutic drug resistance. Osteosarcoma is one of the main bone tumor subtypes that poses a serious threat to adolescent health. We summarized how lncRNAs regulate osteosarcoma progression, invasion, and drug resistance, as well as how lncRNAs can function as biomarkers or independent prognostic indicators with respect to osteosarcoma therapy. PMID- 27685635 TI - Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure. AB - Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production. d-galactosamine plus lipopolysaccharide (GalN/LPS), concanavalin A (ConA), and acetaminophen (APAP) were given to C57BL/6N mice to induce liver injury, respectively, and the pathogenic role of circulating histones was studied. Besides, the protective effect of nonanticoagulant heparin, which can bind histones, was evaluated with in vivo and ex vivo investigations. We observed that circulating histones were significantly increased in patients with ALF, and correlated with disease severity and mortality. Significant systemic inflammation was also pronounced in ALF patients, which were associated with histone levels. ALF patients' sera induced significant L02 cell death and stimulated U937 cells to produce cytokines, which were abrogated by nonanticoagulant heparin. Furthermore, circulating histones were all released remarkably in GalN/LPS, ConA, and APAP treated mice, and associated with high levels of inflammatory cytokines. Heparin reduced systemic inflammation and liver damage in mice, suggesting that it could interfere with histone-associated liver injury. Collectively, these findings demonstrate that circulating histones are critical mediators of systemic inflammation and cellular damage in ALF, which may be potentially translatable for clinical use. PMID- 27685637 TI - Interleukin-13 immune gene therapy prevents CNS inflammation and demyelination via alternative activation of microglia and macrophages. AB - Detrimental inflammatory responses in the central nervous system are a hallmark of various brain injuries and diseases. With this study we provide evidence that lentiviral vector-mediated expression of the immune-modulating cytokine interleukin 13 (IL-13) induces an alternative activation program in both microglia and macrophages conferring protection against severe oligodendrocyte loss and demyelination in the cuprizone mouse model for multiple sclerosis (MS). First, IL-13 mediated modulation of cuprizone induced lesions was monitored using T2 -weighted magnetic resonance imaging and magnetization transfer imaging, and further correlated with quantitative histological analyses for inflammatory cell influx, oligodendrocyte death, and demyelination. Second, following IL-13 immune gene therapy in cuprizone-treated eGFP+ bone marrow chimeric mice, we provide evidence that IL-13 directs the polarization of both brain-resident microglia and infiltrating macrophages towards an alternatively activated phenotype, thereby promoting the conversion of a pro-inflammatory environment toward an anti inflammatory environment, as further evidenced by gene expression analyses. Finally, we show that IL-13 immune gene therapy is also able to limit lesion severity in a pre-existing inflammatory environment. In conclusion, these results highlight the potential of IL-13 to modulate microglia/macrophage responses and to improve disease outcome in a mouse model for MS. GLIA 2016;64:2181-2200. PMID- 27685639 TI - Formation and Dynamics of Electron-Irradiation-Induced Defects in Hexagonal Boron Nitride at Elevated Temperatures. AB - The atomic structure, stability, and dynamics of defects in hexagonal boron nitride (h-BN) are investigated using an aberration-corrected transmission electron microscope operated at 80 kV between room temperature and 1000 degrees C. At temperatures above 700 degrees C, parallelogram- and hexagon-shaped defects with zigzag edges become prominent, in contrast to the triangular defects typically observed at lower temperatures. The appearance of 120 degrees corners at defect vertices indicates the coexistence of both N- and B-terminated zigzag edges in the same defect. In situ dynamics studies show that the hexagonal holes grow by electron-induced sputtering of B-N chains, and that at high temperatures these chains can migrate from one defect corner to another. We complement the experiments with first-principles calculation which consider the thermal equilibrium formation energy of different defect configurations. It is shown that, below a critical defect size, hexagonal defects have the lowest formation energy and therefore are the more-stable configuration, and triangular defects are energetically metastable but can be "frozen in" under experimental conditions. We also discuss the possible contributions of several dynamic processes to the temperature-dependent defect formation. PMID- 27685638 TI - Human exposure to environmental contaminants and congenital anomalies: a critical review. AB - Congenital anomalies are an important cause of infant mortality and disability. Developmental exposure to environmental contaminants is thought to increase the risk for congenital anomalies. Herein, we describe a critical review of the literature conducted between February and March 2014 yielding 3057 references from which 97 unique relevant articles published from 2003 through 2014 were evaluated. Common congenital anomalies including hypospadias, cryptorchidism, anogenital distance (AGD), congenital heart defects and oral clefts were well represented in the literature whereas other outcomes such as neural tube defects, limb deficiency defects and gastroschisis were rarely described. While definitions used for congenital anomalies and methods of ascertainment were usually consistent across studies, inconsistencies were frequently found in grouping of different congenital heart defects. Despite strong links between some congenital anomalies and parental occupation, these studies are unable to provide clear insight into the specific chemicals responsible owing to lack of direct measures of exposure. In comparison, data are mixed for contaminant exposures at concentrations representative of results from contemporary biomonitoring studies. Of the environmental contaminants studied, the association between phthalate exposures and developmental abnormalities of the male reproductive tract received the greatest attention. Important limitations of the literature studied relate to adequacy of sample size, absence of or weaknesses in exposure assessment methodologies, failure to account for biological plausibility and grouping of congenital anomalies with divergent mechanisms. We conclude that the literature is inadequate at this time to support a conclusion that exposure to environmental contaminants are or are not associated with increased risks for congenital anomalies in the general population. PMID- 27685642 TI - Detecting deception in children: A meta-analysis. AB - Although research reveals that children as young as 3 can use deception and will take steps to obscure truth, research concerning how well others detect children's deceptive efforts remains unclear. Yet adults regularly assess whether children are telling the truth in a variety of contexts, including at school, in the home, and in legal settings, particularly in investigations of maltreatment. We conducted a meta-analysis to synthesize extant research concerning adults' ability to detect deceptive statements produced by children. We included 45 experiments involving 7,893 adult judges and 1,858 children. Overall, adults could accurately discriminate truths/lies at an average rate of 54%, which is slightly but significantly above chance levels. The average rate at which true statements were correctly classified as honest was higher (63.8%), whereas the rate at which lies were classified as dishonest was not different from chance (47.5%). A small positive correlation emerged between judgment confidence and judgment accuracy. Professionals (e.g., social workers, police officers, teachers) slightly outperformed laypersons (e.g., college undergraduates). Finally, exploratory analyses revealed that the child's age did not significantly affect the rate at which adults could discriminate truths/lies from chance. Future research aimed toward improving lie detection accuracy might focus more on individual differences in children's lie-telling abilities in order to uncover any reliable indicators of deception. (PsycINFO Database Record PMID- 27685641 TI - Firms' compliance with complex regulations. AB - This study addresses the question of what explains compliance with complex regulations, which are technical, extensive, and often subject to modifications. Based on official (anonymized) data of financial intermediaries in the Netherlands (N = 602), we examined the association between compliance (measured as number of law violations) and the extent to which regulatory complexity is perceived as fair (i.e., the perception that the extensive regulation generates unnecessary difficulties for the firm). We hypothesized that perceiving regulatory complexity as fair would motivate firms to acquire knowledge of the regulation, and that this knowledge in turn would improve their ability to comply. In line with our hypothesis, the results of a series of tests show that knowledge mediates the association between perceived fairness and compliance (95% confidence intervals). These findings indicate that (a) regulatory complexity is not necessarily unfair, (b) the well-established direct association between fairness perceptions and compliance is less straightforward when regulations are highly complex (because it involves a fundamental mediating mechanism), and (c) firms' compliance behavior may respond to not only cost-benefit analyses, but also to fairness perceptions about the law. (PsycINFO Database Record PMID- 27685643 TI - Effects of a proven error on evaluations of witness testimony. AB - Witnesses frequently make an error when reporting events they have observed. Although some error in witness reports is to be expected and does not mean the testimony as a whole is flawed, an important question is how such an error affects judgments of credibility of the witness. In 2 experiments we investigated the impact of a single demonstrated (probative or nonprobative) detail inaccuracy on judgments of the likely reliability of witness memory. Potential mediators (witness dishonesty and forgetfulness) were examined to explain the relationship between inaccuracy and perceived reliability of the witness's memory report. The presence of a single inaccuracy affected observers' judgments of the reliability of the other elements of testimony and the testimony as a whole. There was also some evidence that the less probative the detail the more other elements of the reported account of the event were questioned. The mediation analyses showed that a single testimonial error contributed to the witness being perceived as dishonest or forgetful, attributions that in turn shaped perceptions of witness credibility. These findings suggest that legal professionals should be cautious when highlighting an isolated testimonial error given the potential for it to suggest more widespread testimonial unreliability. (PsycINFO Database Record PMID- 27685640 TI - The RNA Chaperone Hfq Is Involved in Colony Morphology, Nutrient Utilization and Oxidative and Envelope Stress Response in Vibrio alginolyticus. AB - Hfq is a global regulator that is involved in environmental adaptation of bacteria and in pathogenicity. To gain insight into the role of Hfq in Vibrio alginolyticus, an hfq deletion mutant was constructed in V. alginolyticus ZJ-T strain and phenotypically characterized. Deletion of hfq led to an alteration of colony morphology and reduced extracellular polysaccharide production, a general impairment of growth in both rich medium and minimal media with different carbon sources or amino acids, enhanced sensitivity to oxidative stress and to several antibiotics. Furthermore, a differential transcriptomic analysis showed significant changes of transcript abundance for 306 protein coding genes, with 179 genes being up regulated and 127 down-regulated. Several of these changes could be related to the observed phenotypes of the mutant. Transcriptomic data also provided evidence for the induction of the extracytoplasmic stress response in absence of Hfq. Altogether, these findings point to broad regulatory functions for Hfq in V. alginolyticus cells, likely to underlie an important role in pathogenicity. PMID- 27685644 TI - Evaluating lineup fairness: Variations across methods and measures. AB - Triers of fact sometimes consider lineup fairness when determining the suggestiveness of an identification procedure. Likewise, researchers often consider lineup fairness when comparing results across studies. Despite their importance, lineup fairness measures have received scant empirical attention and researchers inconsistently conduct and report mock-witness tasks and lineup fairness measures. We conducted a large-scale, online experiment (N = 1,010) to examine how lineup fairness measures varied with mock-witness task methodologies as well as to explore the validity and reliability of the measures. In comparison to descriptions compiled from multiple witnesses, when individual descriptions were presented in the mock-witness task, lineup fairness measures indicated a higher number of plausible lineup members but more bias toward the suspect. Target-absent lineups were consistently estimated to be fairer than target present lineups-which is problematic because it suggests that lineups containing innocent suspects are less likely to be challenged in court than lineups containing guilty suspects. Correlations within lineup size measures and within some lineup bias measures indicated convergent validity and the correlations across the lineup size and lineup bias measures demonstrated discriminant validity. The reliability of lineup fairness measures across different descriptions was low and reliability across different sets of mock witnesses was moderate to high, depending on the measure. Researchers reporting lineup fairness measures should specify the type of description presented, the amount of detail in the description, and whether the mock witnesses viewed target-present and/or absent lineups. (PsycINFO Database Record PMID- 27685645 TI - Fair lineups are better than biased lineups and showups, but not because they increase underlying discriminability. AB - Receiver Operating Characteristic (ROC) analysis has recently come in vogue for assessing the underlying discriminability and the applied utility of lineup procedures. Two primary assumptions underlie recommendations that ROC analysis be used to assess the applied utility of lineup procedures: (a) ROC analysis of lineups measures underlying discriminability, and (b) the procedure that produces superior underlying discriminability produces superior applied utility. These same assumptions underlie a recently derived diagnostic-feature detection theory, a theory of discriminability, intended to explain recent patterns observed in ROC comparisons of lineups. We demonstrate, however, that these assumptions are incorrect when ROC analysis is applied to lineups. We also demonstrate that a structural phenomenon of lineups, differential filler siphoning, and not the psychological phenomenon of diagnostic-feature detection, explains why lineups are superior to showups and why fair lineups are superior to biased lineups. In the process of our proofs, we show that computational simulations have assumed, unrealistically, that all witnesses share exactly the same decision criteria. When criterial variance is included in computational models, differential filler siphoning emerges. The result proves dissociation between ROC curves and underlying discriminability: Higher ROC curves for lineups than for showups and for fair than for biased lineups despite no increase in underlying discriminability. (PsycINFO Database Record PMID- 27685646 TI - Imaging Anatomical Research on the Operative Windows of Oblique Lumbar Interbody Fusion. AB - To provide applied anatomical evidence of the preoperative assessment of oblique lumbar interbody fusion (OLIF), the anatomical parameters of the OLIF operative window were observed through computed tomography angiography (CTA). We selected imaging data from 60 adults (30 males, 30 females) who underwent abdominal CTA and T12-S1 vertebral computed tomography (CT) with three-dimensional reconstruction. The OLIF operative windows at the L1-2, L2-3, L3-4, L4-5 and L5 S1 levels were as follows: the vascular window, bare window, psoas major window, ideal operative window, and actual operative window. Each level's actual operative window was statistically analyzed based on an actual operative window of <1 cm and >=1 cm. The vascular window was largest at L4-5 (1.72 +/- 0.58 cm). The bare window was largest at L5-S1 (1.59 +/- 0.93 cm) and smallest at L3-4 (1.37 +/- 0.51 cm). The psoas major window was largest at L3-4 (1.14 +/- 0.35 cm) and smallest at L1-2 (0.41 +/- 0.34 cm). The ideal operative window was largest at L4-5 (3.74 +/- 0.36 cm) and smallest at L1-2 (3.23 +/- 0.30 cm). The actual operative window was largest at L3-4, followed by L2-3, L4-5, L1-2, and L5-S1, which were 2.51 +/- 0.56 cm, 2.28 +/- 0.54 cm, 2.01 +/- 0.74 cm, 1.80 +/- 0.45 cm and 1.59 +/- 0.93 cm, respectively (P = 0.000), and the percentages of the actual surgical window were 69%, 66%, 53%, 56% and 43%, respectively. The actual surgical window was <1 cm in 2 cases at L1-2 (3.3%), 4 cases at L4-5 (6.7%), and 17 cases at L5-S1 (28.3%) (11 males and 6 females). The regional anatomy of each level related to OLIF has its own peculiarities, and not all levels are suitable for OLIF. Before OLIF surgery, surgeons should analyze the imaging anatomy and select the appropriate surgical procedures. PMID- 27685648 TI - Transcriptional patterns of reverse remodeling with left ventricular assist devices: a consistent signature. AB - INTRODUCTION: Left ventricular assist device (LVAD) therapy has revolutionized the treatment of patients with advanced heart failure. Although originally intended for bridge-to-transplantation and destination therapy indications, a small subset of patients supported with LVADs exhibit complete myocardial recovery leading to device explanation. However, genetic and molecular determinants of partial and/or complete myocardial recovery remain largely unknown. Areas covered: We summarize current knowledge on alterations in heart failure transcriptome in response to LVAD support, as well as discuss common gene signatures potentially responsible for the reverse remodeling phenotype in the failing human heart. Expert commentary: Reverse remodeling after LVAD is likely a continuum between fully and partially recovered myocardium. Multicenter cardiac tissue repositories linked with detailed phenotype information may facilitate identification of genetic signals responsible for myocardial recovery in LVAD supported patients in the foreseeable future. PMID- 27685647 TI - Adenofection: A Method for Studying the Role of Molecular Chaperones in Cellular Morphodynamics by Depletion-Rescue Experiments. AB - Cellular processes such as mitosis and cell differentiation are governed by changes in cell shape that largely rely on proper remodeling of the cell cytoskeletal structures. This involves the assembly-disassembly of higher-order macromolecular structures at a given time and location, a process that is particularly sensitive to perturbations caused by overexpression of proteins. Methods that can preserve protein homeostasis and maintain near-to-normal cellular morphology are highly desirable to determine the functional contribution of a protein of interest in a wide range of cellular processes. Transient depletion-rescue experiments based on RNA interference are powerful approaches to analyze protein functions and structural requirements. However, reintroduction of the target protein with minimum deviation from its physiological level is a real challenge. Here we describe a method termed adenofection that was developed to study the role of molecular chaperones and partners in the normal operation of dividing cells and the relationship with actin remodeling. HeLa cells were depleted of BAG3 with siRNA duplexes targeting the 3'UTR region. GFP-tagged BAG3 proteins were reintroduced simultaneously into >75% of the cells using recombinant adenoviruses coupled to transfection reagents. Adenofection enabled to express BAG3-GFP proteins at near physiological levels in HeLa cells depleted of BAG3, in the absence of a stress response. No effect was observed on the levels of endogenous Heat Shock Protein chaperones, the main stress-inducible regulators of protein homeostasis. Furthermore, by adding baculoviruses driving the expression of fluorescent markers at the time of cell transduction transfection, we could dissect mitotic cell dynamics by time-lapse microscopic analyses with minimum perturbation of normal mitotic progression. Adenofection is applicable also to hard-to-infect mouse cells, and suitable for functional analyses of myoblast differentiation into myotubes. Thus adenofection provides a versatile method to perform structure-function analyses of proteins involved in sensitive biological processes that rely on higher-order cytoskeletal dynamics. PMID- 27685649 TI - A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus. AB - BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need. PMID- 27685650 TI - Evaluation DNA-/BSA-binding properties of a new europium complex containing 2,9 dimethyl-1,10-phenanthroline. PMID- 27685652 TI - SparkText: Biomedical Text Mining on Big Data Framework. AB - BACKGROUND: Many new biomedical research articles are published every day, accumulating rich information, such as genetic variants, genes, diseases, and treatments. Rapid yet accurate text mining on large-scale scientific literature can discover novel knowledge to better understand human diseases and to improve the quality of disease diagnosis, prevention, and treatment. RESULTS: In this study, we designed and developed an efficient text mining framework called SparkText on a Big Data infrastructure, which is composed of Apache Spark data streaming and machine learning methods, combined with a Cassandra NoSQL database. To demonstrate its performance for classifying cancer types, we extracted information (e.g., breast, prostate, and lung cancers) from tens of thousands of articles downloaded from PubMed, and then employed Naive Bayes, Support Vector Machine (SVM), and Logistic Regression to build prediction models to mine the articles. The accuracy of predicting a cancer type by SVM using the 29,437 full text articles was 93.81%. While competing text-mining tools took more than 11 hours, SparkText mined the dataset in approximately 6 minutes. CONCLUSIONS: This study demonstrates the potential for mining large-scale scientific articles on a Big Data infrastructure, with real-time update from new articles published daily. SparkText can be extended to other areas of biomedical research. PMID- 27685651 TI - Analysis of the Yeast Peptidome and Comparison with the Human Peptidome. AB - Peptides function as signaling molecules in species as diverse as humans and yeast. Mass spectrometry-based peptidomics techniques provide a relatively unbiased method to assess the peptidome of biological samples. In the present study, we used a quantitative peptidomic technique to characterize the peptidome of the yeast Saccharomyces cerevisiae and compare it to the peptidomes of mammalian cell lines and tissues. Altogether, 297 yeast peptides derived from 75 proteins were identified. The yeast peptides are similar to those of the human peptidome in average size and amino acid composition. Inhibition of proteasome activity with either bortezomib or epoxomicin led to decreased levels of some yeast peptides, suggesting that these peptides are generated by the proteasome. Approximately 30% of the yeast peptides correspond to the N- or C-terminus of the protein; the human peptidome is also highly represented in N- or C-terminal protein fragments. Most yeast and humans peptides are derived from a subset of abundant proteins, many with functions involving cellular metabolism or protein synthesis and folding. Of the 75 yeast proteins that give rise to peptides, 24 have orthologs that give rise to human and/or mouse peptides and for some, the same region of the proteins are found in the human, mouse, and yeast peptidomes. Taken together, these results support the hypothesis that intracellular peptides may have specific and conserved biological functions. PMID- 27685655 TI - Perpendicular State of an Electronically Excited Stilbene: Observation by Femtosecond-Stimulated Raman Spectroscopy. AB - In the photoisomerization path of stilbene, a perpendicular state P on the S1 potential energy surface is expected just before internal conversion through a conical intersection S1/S0. For decades the observation of P was thwarted by a short lifetime tauP in combination with slow population flow over a barrier. But these limitations can be overcome by ethylenic substitution. Following optical excitation of trans-1,1'-dicyanostilbene, P is populated significantly (tauP = 27 ps in n-hexane) and monitored by an exited-state absorption band at 370 nm. Here we report stimulated Raman lines of P. The strongest, at 1558 cm-1, is attributed to stretching vibrations of the phenyl rings. Transient electronic states, resonance conditions, and corresponding Raman signals are discussed. PMID- 27685654 TI - Species Determination and Quantitation in Mixtures Using MRM Mass Spectrometry of Peptides Applied to Meat Authentication. AB - We describe a simple protocol for identifying and quantifying the two components in binary mixtures of species possessing one or more similar proteins. Central to the method is the identification of 'corresponding proteins' in the species of interest, in other words proteins that are nominally the same but possess species specific sequence differences. When subject to proteolysis, corresponding proteins will give rise to some peptides which are likewise similar but with species-specific variants. These are 'corresponding peptides'. Species-specific peptides can be used as markers for species determination, while pairs of corresponding peptides permit relative quantitation of two species in a mixture. The peptides are detected using multiple reaction monitoring (MRM) mass spectrometry, a highly specific technique that enables peptide-based species determination even in complex systems. In addition, the ratio of MRM peak areas deriving from corresponding peptides supports relative quantitation. Since corresponding proteins and peptides will, in the main, behave similarly in both processing and in experimental extraction and sample preparation, the relative quantitation should remain comparatively robust. In addition, this approach does not need the standards and calibrations required by absolute quantitation methods. The protocol is described in the context of red meats, which have convenient corresponding proteins in the form of their respective myoglobins. This application is relevant to food fraud detection: the method can detect 1% weight for weight of horse meat in beef. The corresponding protein, corresponding peptide (CPCP) relative quantitation using MRM peak area ratios gives good estimates of the weight for weight composition of a horse plus beef mixture. PMID- 27685656 TI - Generation of VDR Knock-Out Mice via Zygote Injection of CRISPR/Cas9 System. AB - CRISPR/Cas9 system has become a new versatile technology for genome engineering in various species. To achieve targeted modifications at the same site in both human and mice genomes by a CRISPR/Cas9 nuclease, we designed two target sites in conserved regions of vitamin D receptor (VDR) gene, which cover more than 17 kb of chromosome region depending on the species. We first validated the efficacy of single sgRNA mediated gene specific modifications were 36% and 31% in HEK293T cells. Concurrently, targeted of the intervening genomic segments deletions were generated in chromosomes when two sgRNAs worked simultaneously. The large genomic DNA segments up to 23.4 Kb could be precisely deleted in human chromosomes. Subsequently, Cas9 mRNA and sgRNAs targeting VDRT1 and VDRT2 were co microinjected into one-cell-stage embryos of C57BL/6 mice. Verified by T7E1 assay and DNA sequencing analysis, 12 mice showed VDR targeted disruption and 8 of which were biallelic knock-out, which demonstrated obvious phenotype of hair thinning. Furthermore, expression changes of Vitamin D metabolism genes in VDR-/ mice were detected. These results indicated that CRISPR/Cas9 mediated knock-out of VDR diminished its gene function in vivo. The off-target effects of CRISPR/Cas9 in VDR-/- founder mice were analyzed. Our results showed that CRISPR/Cas9 system could be employed to target the same sites in different species, when sgRNAs are designed within conserved regions, and therefore will be critically important and applicable for human disease model. PMID- 27685657 TI - Use of intraoperative CT to predict the accuracy of microelectrode recording during deep brain stimulation surgery. A proof of concept study. AB - OBJECTIVES: Intraoperative computed tomography (iCT) is currently used to confirm the target location of the microelectrode (ME) during microelectrode recording (MER) and ultimate location of deep brain stimulation (DBS) leads at our institution. We evaluated whether iCT can be used to predict the trajectory and accuracy of the ME track. PATIENTS AND METHODS: Intraoperative imaging profiles of ten consecutive patients who had undergone DBS surgery were retrospectively reviewed. We found that cranial iCT, in addition to visualizing the target, also visualizes the extra-cranial segment of the guide tube (ECGT) used to insert the ME. We propose a hypothetical technique that extrapolates the trajectory of only the ECGT down to target depth using planning software. In order to provide a proof of concept analysis of this hypothetical technique, we retrospectively assessed post MER placement iCT studies and used planning software to visualize only the ECGT. An extrapolated vector was drawn along the long axis of the ECGT down to the same depth (z) as the ME. The obtained x and y coordinates were subsequently recorded and compared to the x and y coordinates of the ME tip to validate this technique. RESULTS: The average radial error between ECGT trajectory coordinates and final ME tip coordinates was 0.93+/-0.1mm (mean+/ SEM). CONCLUSION: The use of iCT to predict accuracy of microelectrode location is feasible. In the future, performing iCT before guide tube penetration of dura can allow for trajectory prediction and if needed, correction of the ME, thereby potentially improving accuracy and reducing the number of MER tracks. PMID- 27685658 TI - Clinical outcome and intraoperative neurophysiology for focal limb dystonic tremor without generalized dystonia treated with deep brain stimulation. AB - OBJECTIVES: Dystonic tremor (DT) is defined as a postural/kinetic tremor occurring in the body region affected by dystonia. DT is typically characterized by focal tremors with irregular amplitudes and variable frequencies typically below 7Hz. Pharmacological treatment is generally unsuccessful and guidelines for deep brain stimulation (DBS) targeting and indications are scarce. In this article, we present the outcome and neurophysiologic data of two patients with refractory, focal limb DT treated with Globus Pallidus interna (Gpi) DBS and critically review the current literature regarding surgical treatment of DT discussing stereotactic targets and treatment considerations. PATIENTS AND METHODS: A search of literature concerning treatment of DT was conducted. Additionally, Gpi DBS was performed in two patients with DT and microelectrode recordings for multi unit analysis (MUAs) and local field potentials (LFPs) were obtained. RESULTS: The mean percentage improvement in tremor severity was 80.5% at 3 years follow up. MUAs and LFPs did not show significant differences in DT patients compared with other forms of dystonia or PD except for higher interspikes bursting indices. LFP recordings in DT demonstrated high power at low frequencies with action (<3.5Hz). CONCLUSIONS: Gpi DBS is an effective treatment in patients with focal limb DT without associated generalized dystonia. Intraoperative neurophysiologic findings suggest that DT is part of phenotypic motor manifestations in dystonia. PMID- 27685660 TI - Investigating Rates of Hunting and Survival in Declining European Lapwing Populations. AB - Understanding effects of harvest on population dynamics is of major interest, especially for declining species. European lapwing Vanellus vanellus populations increased from the 1960s until the 1980s and declined strongly thereafter. About 400,000 lapwings are harvested annually and it is thus of high conservation relevance to assess whether hunting was a main cause for the observed changes in lapwing population trends. We developed a multi-event cause-specific mortality model which we applied to a long-term ring-recovery data set (1960-2010) of > 360,000 records to estimate survival and cause-specific mortalities. We found no temporal change in survival over the last 50 years for first-year (FY) and older birds (after first-year; AFY) originating from different ringing areas. Mean survival was high, around 0.60 and 0.80 for FY and AFY individuals, respectively. The proportion of total mortality due to hunting was <0.10 over the study period and the estimated proportion of harvested individuals (kill rate) was <0.05 in each year. Our result of constant survival indicates that demographic processes other than survival were responsible for the pronounced change in lapwing population trends in the 1980s. Our findings lend support to the hypothesis that hunting was not a significant contributor to the large-scale decline of lapwing populations. To halt the ongoing decline of European lapwing populations management should focus on life history stages other than survival (e.g. productivity). Further analyses are required to investigate the contribution of other demographic rates to the decline of lapwings and to identify the most efficient conservation actions. PMID- 27685659 TI - Multimodal Quantitative Phase Imaging with Digital Holographic Microscopy Accurately Assesses Intestinal Inflammation and Epithelial Wound Healing. AB - The incidence of inflammatory bowel disease, i.e., Crohn's disease and Ulcerative colitis, has significantly increased over the last decade. The etiology of IBD remains unknown and current therapeutic strategies are based on the unspecific suppression of the immune system. The development of treatments that specifically target intestinal inflammation and epithelial wound healing could significantly improve management of IBD, however this requires accurate detection of inflammatory changes. Currently, potential drug candidates are usually evaluated using animal models in vivo or with cell culture based techniques in vitro. Histological examination usually requires the cells or tissues of interest to be stained, which may alter the sample characteristics and furthermore, the interpretation of findings can vary by investigator expertise. Digital holographic microscopy (DHM), based on the detection of optical path length delay, allows stain-free quantitative phase contrast imaging. This allows the results to be directly correlated with absolute biophysical parameters. We demonstrate how measurement of changes in tissue density with DHM, based on refractive index measurement, can quantify inflammatory alterations, without staining, in different layers of colonic tissue specimens from mice and humans with colitis. Additionally, we demonstrate continuous multimodal label-free monitoring of epithelial wound healing in vitro, possible using DHM through the simple automated determination of the wounded area and simultaneous determination of morphological parameters such as dry mass and layer thickness of migrating cells. In conclusion, DHM represents a valuable, novel and quantitative tool for the assessment of intestinal inflammation with absolute values for parameters possible, simplified quantification of epithelial wound healing in vitro and therefore has high potential for translational diagnostic use. PMID- 27685662 TI - Quasi-One-Step Six-Electron Electrochemical Reduction of an Octahedral Hexanuclear Molybdenum(II) Cluster. AB - We report for the first time quasi-one-step six-electron electrochemical reduction of a new hexanuclear molybdenum(II) bromide cluster having terminal 3,5 dinitrobenzoate ligands: [Mo6Br8(DNBA)6]2-. The electrochemical responses of the cluster were studied based on cyclic (CV), differential pulse, and normal pulse voltammetries, together with the analytical simulations of the CV and spectroelectrochemistry. CV simulations have revealed that the electrochemical reaction of the cluster proceeds in an EEEEEE scheme, and the potential differences between the two adjacent reduction steps are in the range of 15-30 mV. These potential differences indicate quite smooth and quasi-one-step six electron reduction of the cluster. PMID- 27685661 TI - Comparison of Three Different Methods for Determining Cell Proliferation in Breast Cancer Cell Lines. AB - Measuring cell proliferation can be performed by a number of different methods, each with varying levels of sensitivity, reproducibility and compatibility with high-throughput formatting. This protocol describes the use of three different methods for measuring cell proliferation in vitro including conventional hemocytometer counting chamber, a luminescence-based assay that utilizes the change in the metabolic activity of viable cells as a measure of the relative number of cells, and a multi-mode cell imager that measures cell number using a counting algorithm. Each method presents its own advantages and disadvantages for the measurement of cell proliferation, including time, cost and high-throughput compatibility. This protocol demonstrates that each method could accurately measure cell proliferation over time, and was sensitive to detect growth at differing cellular densities. Additionally, measurement of cell proliferation using a cell imager was able to provide further information such as morphology, confluence and allowed for a continual monitoring of cell proliferation over time. In conclusion, each method is capable of measuring cell proliferation, but the chosen method is user-dependent. PMID- 27685663 TI - Molecular diagnosis and immunotherapy. AB - PURPOSE OF REVIEW: To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. RECENT FINDINGS: As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. SUMMARY: Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice. PMID- 27685665 TI - Design of Potent and Druglike Nonphenolic Inhibitors for Catechol O Methyltransferase Derived from a Fragment Screening Approach Targeting the S Adenosyl-l-methionine Pocket. AB - A fragment screening approach designed to target specifically the S-adenosyl-l methionine pocket of catechol O-methyl transferase allowed the identification of structurally related fragments of high ligand efficiency and with activity on the described orthogonal assays. By use of a reliable enzymatic assay together with X ray crystallography as guidance, a series of fragment modifications revealed an SAR and, after several expansions, potent lead compounds could be obtained. For the first time nonphenolic and small low nanomolar potent, SAM competitive COMT inhibitors are reported. These compounds represent a novel series of potent COMT inhibitors that might be further optimized to new drugs useful for the treatment of Parkinson's disease, as adjuncts in levodopa based therapy, or for the treatment of schizophrenia. PMID- 27685664 TI - The First Report of miRNAs from a Thysanopteran Insect, Thrips palmi Karny Using High-Throughput Sequencing. AB - Thrips palmi Karny (Thysanoptera: Thripidae) is the sole vector of Watermelon bud necrosis tospovirus, where the crop loss has been estimated to be around USD 50 million annually. Chemical insecticides are of limited use in the management of T. palmi due to the thigmokinetic behaviour and development of high levels of resistance to insecticides. There is an urgent need to find out an effective futuristic management strategy, where the small RNAs especially microRNAs hold great promise as a key player in the growth and development. miRNAs are a class of short non-coding RNAs involved in regulation of gene expression either by mRNA cleavage or by translational repression. We identified and characterized a total of 77 miRNAs from T. palmi using high-throughput deep sequencing. Functional classifications of the targets for these miRNAs revealed that majority of them are involved in the regulation of transcription and translation, nucleotide binding and signal transduction. We have also validated few of these miRNAs employing stem-loop RT-PCR, qRT-PCR and Northern blot. The present study not only provides an in-depth understanding of the biological and physiological roles of miRNAs in governing gene expression but may also lead as an invaluable tool for the management of thysanopteran insects in the future. PMID- 27685667 TI - The Effectiveness of Real-Time Feedback with an Audible Pulse: A Preliminary Study in Renal Doppler Ultrasonography. AB - PURPOSE: The effectiveness of real-time feedback using an audible pulse in renal Doppler ultrasonography was evaluated. METHODS: This study was approved by the institutional review board of our hospital. Written informed consent was provided by all volunteers at enrollment. The 26 healthy volunteers enrolled in this study underwent Doppler ultrasound of both kidneys using audible and inaudible pulses in randomized order and at 1-week intervals. Doppler waveforms were obtained at the interlobar or arcuate arteries using a 2-mm Doppler gate. Each session was considered complete when reproducible waveforms were obtained for 5 s in three predefined regions of the kidney. The scan times needed to obtain waveforms of the right and left kidneys were recorded separately. Measurements were compared using a paired t-test and a two-sample Wilcoxon rank-sum test. RESULTS: The total recorded Doppler sonography scan time for each kidney ranged from 33 to 146 s. The mean scan time was 56.83 s (right, 58.19 s; left, 55.46 s) in the audible session and 72.58 s (right, 72.08 s; left, 73.08 s) in the inaudible session. The scan times were significantly shorter in the audible than inaudible session (p<0.001), whereas the difference in the scan times between the right and left kidneys was not significant. The order of the sessions had no effect on the total scan time. CONCLUSION: Real-time feedback using an audible pulse may encourage patient cooperation during breath-holding and can shorten the time needed to perform Doppler ultrasonography. PMID- 27685666 TI - Structures of the Streptococcus sanguinis SrpA Binding Region with Human Sialoglycans Suggest Features of the Physiological Ligand. AB - Streptococcus sanguinis is a leading cause of bacterial infective endocarditis, a life-threatening infection of heart valves. S. sanguinis binds to human platelets with high avidity, and this adherence is likely to enhance virulence. Previous studies suggest that a serine-rich repeat adhesin termed SrpA mediates the binding of S. sanguinis to human platelets via its interaction with sialoglycans on the receptor GPIbalpha. However, in vitro binding assays with SrpA and defined sialoglycans failed to identify specific high-affinity ligands. To improve our understanding of the interaction between SrpA and human platelets, we determined cocrystal structures of the SrpA sialoglycan binding region (SrpABR) with five low-affinity ligands: three sialylated trisaccharides (sialyl-T antigen, 3' sialyllactose, and 3'-sialyl-N-acetyllactosamine), a sialylated tetrasaccharide (sialyl-LewisX), and a sialyl galactose disaccharide component common to these sialoglyans. We then combined structural analysis with mutagenesis to further determine whether our observed interactions between SrpABR and glycans are important for binding to platelets and to better map the binding site for the physiological receptor. We found that the sialoglycan binding site of SrpABR is significantly larger than the sialoglycans cocrystallized in this study, which suggests that binding of SrpA to platelets either is multivalent or occurs via a larger, disialylated glycan. PMID- 27685668 TI - Elevation Pattern in Growth Coherency on the Southeastern Tibetan Plateau. AB - It is generally expected that inter-annual changes in radial growth among trees would be similar to the increase in altitude due to the limitation of increasingly harsher climatic factors. Here, we examine whether this pattern exists in alpine forests on the southeastern Tibetan Plateau. Increment cores were collected from mature trees at the lower, middle and upper limits of balfour spruce (Picea likiangensis var. balfouriana (Rehd. et Wils.) Hillier ex Slsvin) forests at the Buze and Yela Mountains in Basu County, Changdu Prefecture of Tibet, China. The treeline elevations are 4320 m and 4510 m a.s.l. for Buze and Yela, respectively. Tree-ring widths were measured, crossdated, and detrended to obtain a sequence of ring-width indices for each individual sample. Annual growth rate, climate sensitivity, growth-climate relationships, and growth synchrony among trees were calculated and compared across altitudes. In Buze Mountain, the annual growth rate of trees has no significant difference across altitudes. The mean sensitivity of trees is lower at the treelines than at lower elevations. Tree growth has stronger correlation with winter temperature at upper elevations than at lower elevations, has significant correlation with moisture, not temperature, in the growing season, and the growth response to moisture is lower at the treeline than at lower elevations. The correlation among individual tree ring sequences is lower at the treeline than at sites at lower elevation. In Yela Mountain, the characterisitics of annual growth rate, mean sensitivity, tree growth-climate relationships, and inter-serial correlation are similar to those in Buze, but their differences along altitudinal gradients are less significant as those in Buze. Our data do not support the general expectation of growth convergence among individuals with increasing altitude. We conclude that individual heterogeneity and microhabitat diversity are important features for treeline trees that may dampen the growth synchrony in trees. The results obtained in this study expand our knowledge about the pattern of forest growth along altitudinal gradients in high-elevation regions and demonstrate the importance of checking the growth of tree individuals before analyzing the average signal. PMID- 27685669 TI - Prometryn and humic acid induce Cytochrome P450 1A expression in Danio rerio (zebrafish). AB - Humic acid (HA) is a major component of dissolved organic matter, is ubiquitous in the aquatic environment and influences the biological toxicity of organic pollutants. In this study, we investigated the cytochrome P450 1A (CYP 1A) mRNA expression and ethoxyresorufin-O-deethylase (EROD) activity in the gills and liver of zebrafish following exposure to the s-triazine herbicide prometryn with or without HA present. Prometryn induced both CYP 1A mRNA expression and EROD activity. The CYP 1A mRNA expression of zebrafish that were exposed to a combination of prometryn and HA was increased compared to those exposed to prometryn alone. A likely cause for CYP 1A induction is the impact of special components of HA, functioning as aryl hydrocarbon receptor (AHR) agonists. In combination with HA, these increase prometryn levels in tissues. Similar results for EROD activity were evident. In our time course study, CYP 1A mRNA expression reached maximum values during 24h. This revealed CYP 1A mRNA transcription as a comparatively sensitive toxicity index. In a recovery experiment, we found a faster decrease of CYP 1A mRNA expression to control levels (CK) in gills compared to liver tissue. Following exposure to HA, CYP 1A mRNA expression in liver tissue displayed a faster decrease to CK levels. HA induced enhanced metabolic rates for prometryn. In contrast, recovery regularity of CYP 1A expression in gills was independent of the presence of HA. This result indicates different detoxification mechanisms for HA in liver and gills. PMID- 27685670 TI - Broad spectrum screening of 463 organic contaminants in rivers in Macedonia. AB - Target screening of 463 organic contaminants in surface water using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) with direct injection was performed in spring of 2015 in northern Macedonia, at six sampling sites in four rivers belonging to Vardar basin: Kriva, Zletovska, Bregalnica and Vardar. The aim of the study was to differentiate between various types of organic contamination characteristic for different types of anthropogenic activities, such as mining, agriculture, and urbanization. Depending on the studied river, 9-16% of analyzed compounds were detected. The highest total levels of organic contaminants were recorded in agriculturally impacted Bregalnica River (1839-1962ngL-1) and Vardar River downstream from the city of Skopje (1945ngL-1), whereas the lowest level was found in the mining impacted Zletovska River (989ngL-1). The principal organic contaminants of the Bregalnica River were herbicides (45-55% of all detected compounds; 838-1094ngL 1), with the highest concentrations of bentazone (407-530ngL-1) and molinate (84 549ngL-1), common herbicides in rice cultivation. The main organic contaminants in the other rivers were drugs (70-80% of all detected compounds), with antibiotics as a predominant drug class. The highest drug concentrations were measured in the Vardar River, downstream from Skopje (1544ngL-1). Screening of surface water by UHPLC-QTOF-MS was proven as a practical tool for fast collection of comprehensive preliminary information on organic contamination of natural waters, which can present a significant contribution in the monitoring and preservation of good ecological status of freshwater ecosystems. PMID- 27685671 TI - Acute and sub-chronic effects of sub-lethal cadmium exposure on energy metabolism in the freshwater shrimp, Paratya curvirostris. AB - Cadmium (Cd) is a toxic trace element enriched in waters through activities such as mining and agriculture. The freshwater shrimp Paratya curvirostris inhabits near-coastal, lowland streams potentially impacted by Cd, but nothing is known regarding its sensitivity to this metal. An acute (96h) median lethal concentration (LC50) of 405ugL-1 was derived for P. curvirostris, placing it among the most tolerant of freshwater shrimp species. Acute (4 d; 0, 50 and 100ugL-1) and sub-chronic (10 d; 0, 25 and 50ugL-1) exposures then investigated effects of Cd on energy metabolism (respiration rate, excretion rate, O:N ratio). In contrast to effects in previously studied species, Cd induced an increased respiration rate, which when coupled with an unchanged excretion rate, resulted in an increased O:N ratio. These data were explained by an increased reliance on carbohydrate and/or lipid as a metabolic substrate stimulated by increased metabolic costs of toxicant exposure. Similar effects were seen across all time points, although the lowest effective Cd concentration decreased with increased exposure time. Overall, results suggest that Cd is unlikely to be a significant environmental stressor to P. curvirostris, except in highly contaminated freshwaters, and/or where Cd co-occurs with hypoxia. PMID- 27685673 TI - Emerging New Delhi metallo-beta-lactamase-1-type-producing Gram-negative bacteria isolated from Cairo University Pediatric Hospital, Cairo, Egypt. AB - New Delhi metallo-beta-lactamase (NDM) compromises the efficacy of almost all beta-lactam antibiotics, including carbapenems. This study aimed to screen for the blaNDM-1-type gene and NDM-1-type carbapenemase production among Gram negative bacteria in Cairo University Pediatric Hospital (Cairo, Egypt). Among 382 Gram-negative clinical isolates collected over the period October 2013 to May 2014, 100 clinical isolates showing reduced carbapenem (imipenem and meropenem) susceptibility were included in this study. Initial phenotypic screening for NDM enzyme production was performed by Etest for metallo-beta-lactamases (EMBL). Genotypic detection of the blaNDM-1-type gene was done by TaqMan real-time PCR. Metallo-beta-lactamase production was detected in 23% of the isolates by EMBL, whereas 24% of the isolates were found to be positive for the blaNDM-1-type gene by real-time PCR. The EMBL sensitivity was 79.2%, specificity was 94.7%, positive predictive value was 82.6%, negative predictive value was 93.5% and overall accuracy was 91.0%. Seventeen (70.8%) of blaNDM-1-type-positive cases were hospital-acquired in origin, whilst 7 cases (29.2%) were community-acquired. Eleven isolates (45.8%) harbouring blaNDM-1-type were found in critical care units. In conclusion, the high prevalence of blaNDM-1-type carbapenemase gene among Gram-negative bacteria, with its great potential for spread in intensive care units, warrants the attention of a nationwide surveillance programme to contain its spread. PMID- 27685674 TI - Creating the next steps to care: Maternal heath, improvisation, and Fulani women in Niamey, Niger. AB - On paper, Niger's maternal healthcare system is extensively outlined by policies which assure access to certain services and create hierarchical referral chains. In practice it remains intensely improvisational: actors in the system must frequently make up the next steps to giving and receiving care, often outside the existing policies and procedures. Although population health in Niger has improved since the recently enacted gratuite des soins policy (which guarantees free access to certain material and child health services), care on the ground is still dictated by difficult circumstances and scarce resources. Health workers often lack the required medications and supplies; nevertheless, they must find ways to deliver services. Patients seeking maternal health services are frequently dissatisfied with the care they receive and so move forward of their own volition, by negotiating with health workers or by looking for services elsewhere. This research builds on recent scholarly work on improvisation, and asks us to further look at the ways that improvisation can be informed by the identity of the actors. Examining case studies of women from the Fulani ethnic group illustrates how particular cultural differences can inform improvisation. Analysing improvisation can also have policy implications; identifying typical points of departure from the official maternal health care system can reveal points where Niger can bolster its commitment to a universally high quality of care. PMID- 27685672 TI - Nutrient-induced antibiotic resistance in Enterococcus faecalis in the eutrophic environment. AB - Nutrient deposition and extensive use of antibiotics are increasing worldwide, especially in freshwater ecosystems. Bacteria display resistance to certain antibiotics and thus survive for extended periods in eutrophic environments. In this study, model ecosystems were established to investigate the effect of nitrate and phosphate nutrient salts on antibiotic resistance in strains of Enterococcus faecalis. Mesocosms were replicated to evaluate the ecological effects of nutrient influx. The mesocosms were divided into four different nitrogen (N) and phosphorus (P) regimens. Enterococcus faecalis strains were isolated on Days 0, 1, 7, 14, 21, 28, 40, 60 and 95 to evaluate their sensitivity to ampicillin, oxytetracycline (OXY), ciprofloxacin (CIP), chloramphenicol (CHL), vancomycin and erythromycin (ERY). Resistance genes for ERY (ermB, msrC and mefA), OXY [tet(M), tet(L) and tet(S)] and CHL (cat) as well as the enterococcal surface protein gene (esp) were investigated by PCR. The total nitrogen, total phosphorus, chemical oxygen demand permanganate index (CODMn), chlorophyll-a, Secchi depth and trophic level index were observed. In conclusion, addition of N and P had a significant influence on the resistance phenotypes of E. faecalis to OXY, CHL and ERY. Only high dosage led to CIP resistance. Higher total N concentrations resulted in the development of relatively higher resistance to OXY and CIP. The resistance genes tet(L) and tet(S) for OXY, msrC for ERY and cat for CHL were found to be associated with resistance in E. faecalis. PMID- 27685675 TI - Correspondence. PMID- 27685676 TI - QUALITATIVE AND QUANTITATIVE FOLLOW-UP USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL VEIN OCCLUSION TREATED WITH ANTI-VEGF: Optical Coherence Tomography Angiography Follow-up of Retinal Vein Occlusion. AB - PURPOSE: To evaluate changes of vascular flow of patients treated with intravitreal injections of anti-vascular endothelial growth factor for macular edema secondary to retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA). METHODS: Patients with RVO with macular edema and treated with intravitreal injections of anti-vascular endothelial growth factors were retrospectively evaluated. The following examinations were performed before and after treatment: best-corrected visual acuity, spectral domain optical coherence tomography, fluorescein angiography, and OCTA (Optovue, Inc). Automatic measurement of vascular density of the superficial and deep capillary plexus was also performed and compared with age- and sex-matched healthy subjects. RESULTS: Twenty-eight eyes of 28 patients (mean age 66.2 years; males 19%) were evaluated, including 13 central RVO, 11 branch RVO, and 4 hemicentral RVO. After treatment, mean central macular thickness significantly decreased from 644 MUm to 326 MUm and best-corrected visual acuity increased from 20/125 to 20/63 (P < 0.01 for both results). On OCTA, perifoveal capillary disruption (P = 0.029) and the number of cysts in the superficial capillary plexus and deep capillary plexus (P < 0.002) significantly decreased after treatment. The mean vascular density in the superficial capillary plexus slightly decreased during follow-up from 46.44% to 45.01% (not significantly). These densities were significantly less than those observed in healthy controls (P < 0.001). CONCLUSION: Optical coherence tomography angiography showed regression of macular edema, reduced capillary disruption and cysts, and slight decrease in mean macular vascular density with time and despite treatment. Thus, OCTA enables qualitative and quantitative evaluation during follow-up of patients treated for RVO. PMID- 27685679 TI - External Drainage for Primary Surgical Management of Uveal Melanoma Exudative Retinal Detachment. PMID- 27685682 TI - Commentary on Zeremski et al. (2016): Improvements in HCV-related Knowledge Among Substance Users on Opioid Agonist Therapy After an Educational Intervention. PMID- 27685680 TI - A One-Hole Cu4S Cluster with N2O Reductase Activity: A Structural and Functional Model for CuZ. AB - During bacterial denitrification, two-electron reduction of N2O occurs at a [Cu4(MU4-S)] catalytic site (CuZ*) embedded within the nitrous oxide reductase (N2OR) enzyme. In this Communication, an amidinate-supported [Cu4(MU4-S)] model cluster in its one-hole (S = 1/2) redox state is thoroughly characterized. Along with its two-hole redox partner and fully reduced clusters reported previously, the new species completes the two-electron redox series of [Cu4(MU4-S)] model complexes with catalytically relevant oxidation states for the first time. More importantly, N2O is reduced by the one-hole cluster to produce N2 and the two hole cluster, thereby completing a closed cycle for N2O reduction. Not only is the title complex thus the best structural model for CuZ* to date, but it also serves as a functional CuZ* mimic. PMID- 27685681 TI - Creation of Abdominal Adhesions in Mice. AB - Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or intraabdominal infection. The precise mechanisms underlying adhesion formation are poorly understood. Many compounds and physical barriers have been tested for their ability to prevent adhesions after surgery with varying levels of success. The mouse and rat are important models for the study of abdominal adhesions. Several different techniques for the creation of adhesions in the mouse and rat exist in the literature. Here we describe a protocol utilizing abrasion of the cecum with sandpaper and sutures placed in the right abdominal sidewall. The mouse is anesthetized and the abdomen is prepped. A midline laparotomy is created and the cecum is identified. Sandpaper is used to gently abrade the surface of the cecum. Next, several figure-of-eight sutures are placed into the peritoneum of the right abdominal sidewall. The abdominal cavity is irrigated, a small amount of starch is applied, and the incision is closed. We have found that this technique produces the most consistent adhesions with the lowest mortality rate. PMID- 27685685 TI - Doctors At Greater Risk Of A Malpractice Claim. PMID- 27685684 TI - Society News: ASAM Magazine. PMID- 27685683 TI - Response to Commentary on Zeremski et al. (2016): Improvements in HCV-related Knowledge Among Substance Users on Opioid Agonist Therapy After an Educational Intervention. PMID- 27685686 TI - The Role Of Medical Personnel In Sports Concussion. PMID- 27685687 TI - DVT presentations to an Emergency Department: A study of guideline based care and decision making. AB - Pre-test probability scoring and blood tests for deep venous thrombosis (DVT) assessment are sensitive but not specific leading to increased demands on radiology services. 385 patients presenting to an Emergency Department with suspected DVT were studied to explore our actual work up of patients with possible DVT relating to risk stratification, further investigation and follow up. Of the 205 patients with an initially negative scan, 36 (17.6%) were brought for review to the Emergency Department Consultant clinic. 34 (16.6%) patients underwent repeat compression ultrasound with 5 (2.4%) demonstrating a DVT on the second scan. Repeat compression ultrasound scans were performed on 34 (16.6%) of patients with an initially negative scan with essentially the same diagnostic yield as other larger studies where 100% of such patients had repeat scanning. Where there is ongoing concern, repeat above knee compression ultrasound within one week will pick up a small number of deep venous thromboses. PMID- 27685688 TI - Myasthenia gravis: a population-based epidemiological study. AB - Myasthenia Gravis (MG) is a disorder affecting components of the neuromuscular junction. Epidemiological studies show rising incidence and prevalence rates. The aim of this study was to determine the incidence and prevalence of MG in the Republic of Ireland. Data sources included patient lists from consultant neurologists and ophthalmologists, a neuroimmunology laboratory, general practitioners and the Myasthenia Gravis Association. A total of 1715 cases were identified, of which 706 definite, probable or possible autoimmune and congenital MG cases were included. The overall prevalence rate from the data obtained is 15.38/100,000. The study demonstrated a female preponderance (female:male of 1.3: 1) and some geographical variation within Ireland. The average incidence rate for the years 2000 to 2009 was 11.3 per year; the rate for the current decade is 18 per year. The increasing number of diagnoses may be due to improved access to diagnostic investigations and increasing awareness of the clinical manifestations. PMID- 27685689 TI - Bevacizumab compared with diode laser in stage 3 posterior retinopathy of prematurity: A 5 year follow up. AB - We conducted a prospective randomized study to compare outcomes of intravitreal Bevacizumab versus diode laser in thirty eyes of fifteen premature babies with zone 1 or posterior zone 2 retinopathy of prematurity (ROP). We recorded complications, regression/reactivation of ROP, visual outcome, refractive error and systemic complications. The Bevacizumab treated eyes showed rapid regression of the ROP with resolution of plus disease and flattening of the ridge at 48 hours post injection. In 3 Bevacizumab treated eyes, reactivation occurred and were treated with laser (3 eyes) or a further Bevacizumab injection (1 eye). Of the diode laser treated eyes, one showed progression and was treated with Bevacizumab. At 5 year follow up, good outcomes were observed in both treatment groups. Hoever, less myopia was found in the Bevacizumab compared with the diode laser treated eyes. PMID- 27685690 TI - A National Survey on the Diagnosis and Treatment of Paediatric Growth Hormone Deficiency. AB - Many countries have established regulations regarding growth hormone (GH) treatment in children, to standardise care and reduce cost. In this study, we describe current practice in Ireland surrounding child measurement and the approach to diagnosis of GH deficiency. A questionnaire was sent to 139 paediatricians in Ireland and 35 (9 paediatric endocrinologists) responded. Only 13 (37.1%) use the recommended 2-person technique for measuring children under 2. Amongst GH prescribers, there were a variety of GH Stimulation Tests used, sex steroid priming was used by 8 (80%) and the general cut off for a passed test was consistent (7ng/ml). Brand rotation (n=5, 50%) and cost (n=3, 30%) were the most common criteria for deciding the formulation of GH prescribed. We recommend that departments review their child measurement technique and equipment. We also advise the establishment of national guidelines for the use of GH, and a prospective registry for GH treated children. PMID- 27685691 TI - Reporting of Acute Flaccid Paralysis in Children under 15 years of age: Improving Surveillance, January 2009 - December 2014. AB - Acute Flaccid Paralysis (AFP) surveillance, including case investigation and specimen collection is a gold standard method for poliomyelitis surveillance. The expected annual non-polio AFP rate <15 years of age in Ireland is = 1/100 000 population. This study reviewed all cases of AFP reported to the Irish Paediatric Surveillance Unit and the Health Protection Surveillance Centre between January 2009 and December 2014 and compared reporting rates with the expected incidence rate annually. We assessed quality of surveillance data in terms of completeness of investigation for each case reported. Forty-three AFP cases in children <15 years were notified; 35 of which were confirmed. Guillain-Barre Syndrome (GBS) accounted for 48.6% (n=17) of AFP notifications. In 2014, the expected annual AFP target rate was reached. This study identified possible under-reporting of AFP paediatric cases in Ireland between 2009-2013. Completeness of investigations has improved over time, but requires further work. PMID- 27685692 TI - Healthcare utilisation among cancer survivors over 50 years of age. AB - There are now over 104,000 people living in Ireland with a cancer diagnosis. Using The Irish Longitudinal Study on Ageing (TILDA), healthcare utilisation of cancer survivors (aged 50 +) was compared with those without a history of cancer across service providers. Our cancer variable was stratified by time since diagnosis (2-5, 6-10, 11+ years) and type (breast, prostate, colorectal and a miscellaneous group of other cancers). While the probability of cancer survivors accessing GP services was not significant different to respondents without a history of cancer, the probability of an outpatient specialist office visit was 19.5, 11.8 and 14.0 percentage points higher, respectively for those 2-5years, 6 10 years and 11 years or more after their cancer diagnosis and was statistically significant. In Ireland, the pattern of GP and specialist use appears less well defined compared to other European countries. This suggests an overarching policy response is required for cancer survivorship care. PMID- 27685693 TI - Flexible Fiberoptic Bronchoscopy Service; An aid to patient management. AB - The study illustrates advantages of Fiberoptic Bronchoscopy, a new service started at St. Lukes General Hospital in patient care since April 2014. Retrospective review of Bronchoscopies and referrals to Tertiary care unit for Bronchoscopy, prior and after initiation of service at St. Lukes Hospital were studied. Total 106 procedures were performed out of which 103(98%) were for diagnostic purpose. Common Indications for bronchoscopy were functional airway assessment in 38 cases (35%) of chronic cough, 26 cases (24.8%) of suspected Malignancy. The average time taken for procedure was 15 + 1 minute with overall rate of complication recorded in 1 case (0.95%). 32(30%) inpatients were referred before Bronchoscopy services were started locally.15(14%) patients were referred for Endobronchial ultrasound (EBUS) after diagnostic procedure performed at St. Lukes Hospital. To conclude, Bronchoscopy is a safe procedure used for diagnosis of various Lung conditions. The services offered locally reduced the time and cost involved in referrals. The diagnostic Bronchoscopies performed for Malignancy at St. Lukes Hospital have rightly increased references for EBUS at Tertiary care Unit. PMID- 27685695 TI - Bayesian Analysis of Blood Transfusion in Dracula. PMID- 27685694 TI - Utilization and Yield of Nerve Conduction Studies and Electromyography in Older Adults. AB - Older adults are at increased risk of both central and peripheral neurological disorders. Impaired nerve and muscle deficits contribute to morbidity and reduced quality of life. Our aim was to define the utilization and yield of nerve conduction studies (NCS) and electromyography (EMG) in older adults. We reviewed NCS and EMG records for all patients older than age 65 in the year 2012. Of 1,530 NCS and EMGs performed, 352 (23%) were in patients older than 65 (mean age 73.7, 52% male). 288 (83.7%) of NCS were abnormal as were 102 (71.8%) of EMGs. The likelihood of having an abnormal test result increased with increasing age. The most common diagnosis was peripheral neuropathy 231 (65.4%). The incidence of peripheral neuropathy is particularly high in this age group and detection is vital to prevent morbidity and improve quality of life. PMID- 27685696 TI - Vaccination in Renal Transplant Patients (VcRtp study). PMID- 27685698 TI - Planning the Future of Ireland's Healthcare. PMID- 27685697 TI - Beware of the devastating pulmonary aspergillosis syndromes in certain environments. PMID- 27685699 TI - Paediatrics and Child Health in General Practice: the trainees' perspective. PMID- 27685700 TI - Fabricating Cotton Analytical Devices. AB - A robust, low-cost analytical device should be user-friendly, rapid, and affordable. Such devices should also be able to operate with scarce samples and provide information for follow-up treatment. Here, we demonstrate the development of a cotton-based urinalysis (i.e., nitrite, total protein, and urobilinogen assays) analytical device that employs a lateral flow-based format, and is inexpensive, easily fabricated, rapid, and can be used to conduct multiple tests without cross-contamination worries. Cotton is composed of cellulose fibers with natural absorptive properties that can be leveraged for flow-based analysis. The simple but elegant fabrication process of our cotton-based analytical device is described in this study. The arrangement of the cotton structure and test pad takes advantage of the hydrophobicity and absorptive strength of each material. Because of these physical characteristics, colorimetric results can persistently adhere to the test pad. This device enables physicians to receive clinical information in a timely manner and shows great potential as a tool for early intervention. PMID- 27685701 TI - Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms. AB - Importance: Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. Objective: To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. Design, Setting, and Participants: A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs. The study was conducted from October 31, 2013, to January 28, 2016. Interventions: Individuals completed questionnaires regarding ocular symptoms (5-Item Dry Eye Questionnaire [DEQ5], Ocular Surface Disease Index [OSDI], and Neuropathic Pain Symptom Inventory modified for the eye [NPSI-E]), psychological status, and medication use and underwent an ocular surface examination. The QST metrics included measures of vibratory and thermal thresholds and cold and hot pain temporal summation (surrogate measures of central sensitization) on the forearm. Main Outcomes and Measures: Correlations among DE and ocular pain symptom severity with QST metrics measured on the forearm. The OSDI score ranges from 0 to 100, with 100 indicating the most severe DE symptoms. The DEQ5 score ranges from 0 to 22, with the highest score indicating the most severe symptoms, and the NPSI-E score ranges from 0 to 100, with the highest score indicating the most severe symptoms. Psychological state was measured with the 9-item Patient Health Questionnaire, the PTSD Checklist Military Version for PTSD, and the Symptom Checklist-90 for anxiety. Results: Of the 118 patients who participated in the study, 105 (88.9%) were men (mean [SD] age, 60 [10] years), and a mean of 41% had PTSD, 10% depression, and 0.93% anxiety. Using stepwise linear regression analyses, significant associations were identified between overall DE symptom severity and posttraumatic stress disorder scores and tear breakup time (DEQ5 model: R = 0.54; OSDI model: R = 0.61, P < .001). All other variables (ie, demographics, comorbidities, medications, tear film factors, and QST metrics) dropped out of these models. When specifically considering neuropathic-like qualities of DE pain, however, anxiety and hot pain temporal summation at the forearm explained 17% of the variability in ocular burning (R = 0.41; P < .001), and PTSD score, tear breakup time, and hot pain temporal summation at the forearm explained 25% of the variability in sensitivity to wind (R = 0.50; P < .001) and 30% of the variability in total NPSI-E scores (R = 0.55; P < .001). Conclusions and Relevance: Our findings demonstrate that neuropathic-like DE pain symptom severity correlates with quantitative measures of pain sensitivity at a site remote from the eye. This result provides additional evidence that DE symptoms are not only manifestations of a local disorder but also involve somatosensory dysfunction beyond the trigeminal system. PMID- 27685702 TI - Low-level laser therapy with helium-neon laser improved viability of osteoporotic bone marrow-derived mesenchymal stem cells from ovariectomy-induced osteoporotic rats. AB - The purpose of this study was to evaluate the influences of helium-neon (He-Ne) and infrared (IR) lasers on the viability and proliferation rate of healthy and ovariectomy-induced osteoporotic (OVX) bone marrow mesenchymal stem cells (BMMSCs) in vitro. MSCs harvested from the BM of healthy and OVX rats were culture expanded. He-Ne and IR lasers were applied three times at energy densities of 0.6, 1.2, and 2.4??J/cm2 for BMMSCs. BMMSCs viability and proliferation rate were evaluated by MTT assay on days 2, 4, 6, 14, and 21. The results showed that healthy BMMSCs responded optimally to 0.6??J/cm2 using an IR laser after three times of laser radiation. Moreover, it was found that OVX BMMSCs responded optimally to 0.6??J/cm2 with He-Ne laser and one-time laser radiation. It is concluded that the low-level laser therapy (LLLT) effect depends on the physiological state of the BMMSCs, type of the laser, wavelength, and number of laser sessions. The biostimulation efficiency of LLLT also depends on the delivered energy density. LLLT can enhance the viability and proliferation rate of healthy and especially osteoporotic autologous BMMSCs, which could be very useful in regenerative medicine. PMID- 27685703 TI - Aberrant methylation of nucleotide excision repair genes is associated with chronic arsenic poisoning. AB - OBJECTIVE: To define whether aberrant methylation of DNA repair genes is associated with chronic arsenic poisoning. METHODS: Hundred and two endemic arsenicosis patients and 36 healthy subjects were recruited. Methylight and bisulfite sequencing (BSP) assays were used to examine the methylation status of ERCC1, ERCC2 and XPC genes in peripheral blood lymphocytes (PBLs) and skin lesions of arsenicosis patients and NaAsO2-treated HaCaT cells. RESULTS: Hypermethylation of ERCC1 and ERCC2 and suppressed gene expression were found in PBLs and skin lesions of arsenicosis patients and was correlated with the level of arsenic exposure. Particularly, the expression of ERCC1 and ERCC2 was associated with the severity of skin lesions. In vitro studies revealed an induction of ERCC2 hypermethylation and decreased mRNA expression in response to NaAsO2 treatment. CONCLUSION: Hypermethylation of ERCC1 and ERCC2 and concomitant suppression of gene expression might be served as the epigenetic marks associated with arsenic exposure and adverse health effects. PMID- 27685704 TI - A cognitive-based model of tool use in normal aging. AB - While several cognitive domains have been widely investigated in the field of aging, the age-related effects on tool use are still an open issue and hardly any studies on tool use and aging is available. A significant body of literature has indicated that tool use skills might be supported by at least two different types of knowledge, namely, mechanical knowledge and semantic knowledge. However, neither the contribution of these kinds of knowledge to familiar tool use, nor the effects of aging on mechanical and semantic knowledge have been explored in normal aging. The aim of the present study was to fill this gap. To do so, 98 healthy elderly adults were presented with three tasks: a classical, familiar tool use task, a novel tool use task assessing mechanical knowledge, and a picture matching task assessing semantic knowledge. The results showed that aging has a negative impact on tool use tasks and on knowledge supporting tool use skills. We also found that aging did not impact mechanical and semantic knowledge in the same way, confirming the distinct nature of those forms of knowledge. Finally, our results stressed that mechanical and semantic knowledge are both involved in the ability to use familiar tools. PMID- 27685705 TI - Video-assisted thoracic surgery for left upper lobectomy for complex lesions: how to extend the indication with optimal safety? AB - The feasibility of extending the VATS approach to locally advanced NSCLC has been described with good clinical outcome. These complex resections are still technically challenging and patient safety must remain the highest priority. In this article, we describe our routine VATS approach for left upper lobectomy in proximal, locally advanced lesions. Both surgical and anaesthesiology teams are trained during simulation sessions to respond rapidly in case of urgent thoracotomy. Encircling arterial and venous vessels allow control of inadvertent bleeding during difficult dissection. Also, whenever needed the double vessel control technique is a time saver waiting for conversion to thoracotomy. PMID- 27685707 TI - Miscarriage at advanced maternal age and the search for meaning. AB - Although it has been documented that miscarriage is a common pregnancy outcome and more likely to happen among women aged 35 years and older, there is very little research on the quality of such a lived experience. This study features phenomenological interviews of 10 women aged 35 years and older. Theoretical frameworks of ambiguous loss and feminism guide the design and analysis. The salient themes suggest that women experience miscarriage from a physical, emotional, temporal, and social context that includes intense loss and grief, having a sense of otherness, a continuous search for meaning, and feelings of regret and self-blame. PMID- 27685706 TI - SFRP2 Is Associated with Increased Adiposity and VEGF Expression. AB - AIMS: The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to explore its relationship to fat mass, glycaemia and insulin resistance. METHODS: Expression of sFRP2 in mouse and human tissues was assessed using polymerase chain reaction and Western blot. Western blot confirmed secretion of sFRP2 by adipose tissue into cell culture medium. Effects of recombinant sFRP2 on lipogenesis and preadipocyte proliferation were measured. Preadipocyte expression of the angiogenic genes vascular endothelial growth factor (VEGF) and nuclear factor of activated T-cells 3 (NFATC3) was measured after recombinant sFRP2 exposure. Complementary clinical studies correlating human serum sFRP2 with age, gender, adiposity and insulin secretion were also performed. RESULTS: sFRP2 messenger RNA (mRNA) was expressed in mouse and human adipose tissue. In humans, sFRP2 mRNA expression was 4.2-fold higher in omental than subcutaneous adipose. Omental adipose tissue secreted 63% more sFRP2 protein than subcutaneous. Treatment with recombinant sFRP2 did not impact on lipogenesis or preadipocyte proliferation but was associated with increased VEGF mRNA expression. In human subjects, circulating insulin levels positively correlated with serum sFRP2, and levels were higher in patients with abnormal glucose tolerance (34.2ng/ml) compared to controls (29.5ng/ml). A positive correlation between sFRP2 and BMI was also observed. CONCLUSIONS: Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression. PMID- 27685709 TI - Are we moving from absence of proof to proof of absence? PMID- 27685708 TI - Quantum-Transport Characteristics of a p-n Junction on Single-Layer TiS3. AB - By using density functional theory and non-equilibrium Green's function-based methods, we investigated the electronic and transport properties of a TiS3 monolayer p-n junction. We constructed a lateral p-n junction on a TiS3 monolayer using Li and F adatoms. An applied bias voltage caused significant variability in the electronic and transport properties of the TiS3 p-n junction. In addition, the spin-dependent current-voltage characteristics of the constructed TiS3 p-n junction were analyzed. Important device characteristics were found, such as negative differential resistance and rectifying diode behaviors for spin polarized currents in the TiS3 p-n junction. These prominent conduction properties of the TiS3 p-n junction offer remarkable opportunities for the design of nanoelectronic devices based on a recently synthesized single-layered material. PMID- 27685710 TI - A Charge-Transfer-Induced Self-Healing Supramolecular Hydrogel. AB - In this study, a dual-component charge-transfer (CT)-induced supramolecular hydrogel was fabricated using pyrene-tailored pyridinium (PYP) and 2,4,7 trinitrofluorenone (TNF) as the electron donor and acceptor, respectively. Its thermal stability and mechanical property have been modulated effectively by altering the concentration or molar ratio of PYP and TNF. Moreover, this CT hydrogel exhibited a distinct injectable self-healing property that could be utilized to create desired patterns on substrates. Such property holds potential for this CT hydrogel in fields like three-dimensional printing and surface coating. PMID- 27685711 TI - Thesaurus project launched. AB - A two-year project to develop a 'nursing thesaurus', offering unambiguous, standardised terminology for use in health care, was launched last week by the NHS Management Executive. PMID- 27685712 TI - Survey shows poor health for England. AB - The damning findings of the first government survey of the nation's health underline the importance of nurses' involvement in health promotion, unions claimed last week. PMID- 27685713 TI - ? AB - Suffer the little children: Lydia Burke, a practice nurse from Hackney, addresses a public meeting for parents protesting against the outcome of the recent specialty review of paediatric services in London, which proposes re-siting the Queen Elizabeth Hospital to the Royal London Hospital. Parents fear the plans will leave Hackney with no hospital services for children. PMID- 27685714 TI - Committee rejects forceful approach. AB - The Commons Health Select Committee is today expected to reject Health Secretary Virginia Bottomley's proposal for community supervision orders compelling people with severe mental health problems to comply with treatment. Mrs Bottomley's call followed an incident at London Zoo in which a man reportedly suffering from schizophrenia was injured after entering the lions' enclosure. Tom Sandford, RCN Adviser in Mental Health, said: 'This is good news for mental health users and community psychiatric nurses, and for civil rights in this country: ' He called for more funding for community mental health services and the promotion of alternative treatments acceptable to users. PMID- 27685715 TI - Prophit slams 'grossly distorted' reports. AB - Former Edinburgh University Professor of Nursing Penny Prophit has hit back at allegations which questioned her academic credibility. And in a dramatic development, she has been appointed International Visiting Professor to the Colorado-based Centre for Human Caring, which has an affiliate centre in Scotland. PMID- 27685717 TI - 200 healthcare posts at risk. AB - Up to 200 jobs could be lost at Grimsby Health Trust in a bid to recover a L2 million budget deficit, unions claimed last week. And management have agreed that nursing redundancies are unavoidable. PMID- 27685718 TI - London Trust to axe nursing jobs. AB - A North London Trust with a L4 million deficit is set to make nearly 70 staff redundant, it emerged last week. PMID- 27685719 TI - Complaints soar as nurses blamed for poor paperwork. AB - Complaints received by the Health Service Commissioner have reached record levels, with the situation exacerbated by nurses' poor record keeping. PMID- 27685720 TI - Nursing managers are told: 'hierarchy is stifling change'. AB - Senior nursing managers have been urged to 'dump the hierarchy' in a bid to make health services more responsive to change. PMID- 27685721 TI - Leap in Welsh incidence of Hepatitis A shows rising poverty. AB - The incidence of Hepatitis A in Wales has increased more than five-fold in four years. PMID- 27685722 TI - Hospitals urged to drop dated values. AB - Old-fashioned public sector attitudes mean hospitals are throwing away opportunities for service innovation that would benefit both NHS and private patients, a leading marketing expert has claimed. PMID- 27685723 TI - ? AB - Countries in South America are striving to reach the World Health Organization's goal of 'Health for all by the year 2000' through a comprehensive primary care strategy developed at local level under the guidance of the Pan American Health Organisation. The PAHO says, in the fourth of a series of reports on 'Communicating for Health', that the urgent need to improve the health status of economically and socially disadvantaged parts of the population ranks high among the challenges facing the region. PMID- 27685725 TI - NALGO urges more accountability. AB - A 'middle tier of accountability' should be retained within the NHS to counter damaging aspects of the new reforms, NALGO claimed last week. PMID- 27685726 TI - ? AB - Art on the tiles: Patients from St Ann's Hospital, in London, aided by art student Sam Taft (above), have designed a range of ceramic tiles to brighten up the hospital's corridors. Twenty patients joined hi the Haringey Community Arts project. PMID- 27685727 TI - World news. AB - More than 15 million 15-19 year olds become pregnant worldwide every year, with one in three teenage pregnancies ending in abortion, a new survey reveals. PMID- 27685728 TI - NHS pays the price. AB - Unemployment and the fear of redundancy are costing the NHS more than L70 million each year in GP visits and prescription costs, according to a report from the Office of Health Economics. PMID- 27685729 TI - Fibre may inhibit effect of antidepressants. AB - If a patient's depression fails to be relieved by seemingly adequate doses of antidepressants it may be worth enquiring about his or her diet. PMID- 27685730 TI - Pen torch useful in diagnosis of red eye. AB - A simple test with a pen torch may help to distinguish between mild and serious ocular problems in patients who present with unilateral red eye. PMID- 27685731 TI - MRI helps in diagnosis of multiple sclerosis. AB - Magnetic resonance imaging (MRI) can help in the diagnosis of multiple sclerosis, but not to exclude it. PMID- 27685732 TI - Gains in quality of life following angioplasty. AB - Patients can gain significant improvements in their perceived quality of life and health-related quality of life following percutaneous transluminal coronary angioplasty (PTCA). PMID- 27685733 TI - Test identifies type of renal failure. AB - Measurement of carbamylated haemoglobin can be useful in differentiating between patients with acute or chronic renal failure. PMID- 27685734 TI - In the wake of the Braer. AB - Lis Cook, a Shetland-based district nurse/midwife, was in the middle of a well deserved holiday on January 5. The excitement of the New Year festivities was beginning to wane, the weather was ferocious and she was wondering how to keep her four children occupied. A friend rang with the answer: a dramatic air-sea rescue was being mounted just off the west coast of the South Mainland where she lives. This type of rescue is usually spectacular, so Lis quickly got her children into the car and drove to Garths Ness to watch the action. By the time they got there, it was obvious that no rescue was on the go. PMID- 27685735 TI - The cost of caring. AB - What happens when I can no longer cope l with looking after my wife at home? She W I would have to go into a residential nursing home where the fees would be upwards of L400 a week, at a conservative guess. So, I am being paid L33.70 a week to do a job that would otherwise cost L400 a week plus. Is that fair?' PMID- 27685736 TI - Trends in managing schizophrenia. AB - Aims The aims of this article are to inform the reader of recent advances in the concepts related to schizophrenia, and in the care and treatment of people with schizophrenia. PMID- 27685737 TI - Did I call NHS nurses overpaid? AB - A few months ago, I wrote that NHS nurses are overpaid for the work they do (Level of skills in nursing homes, March 3). PMID- 27685738 TI - Pain in Spain needs no restraints. AB - I cannot adequately describe my frustration and anger at the treatment of delegates to the International Council of Nurses' Congress in Madrid. PMID- 27685739 TI - For better or worse, vive la difference. AB - I have just read the thoroughly depressing article, 'Ordinariness in nursing: a study'(Clinical, June 16). Dissections and post mortems are, by comparison, cheerful. PMID- 27685740 TI - In praise of the RCN's plea for involvement. AB - I should like to challenge the assumptions Ann Catlow made in arguing against the training of health care assistants under the patient focused hospitals initiative to perform tasks normally undertaken by 'skilled professionals such as phlebotomists'. PMID- 27685741 TI - Moral slingshots in ethical glass houses. AB - Last week I watched Joan Bakewell on BBC television as she explored the issues surrounding some clinicians' decisions to refuse to treat people who fail to comply with the stipulation that they give up smoking. PMID- 27685742 TI - No U-turn, and focus is firmly on patients. AB - I would take issue with Ann Catlow's claim that the RCN has done a U-turn on its attitudes towards patient focused hospitals (June 2). PMID- 27685744 TI - Setting the research record straight. AB - Your news feature, Team spirit (June 23), though a well- presented and accurate report on the community research project I co-ordinate, contained one error that reflects badly on standards of care in Dorset. The article stated: 'More than a third [of clients] had pressure sores.' PMID- 27685743 TI - Concern over violent attacks warranted. AB - Mike George is right to be concerned about the underreporting of violent attacks on staff (News features, June 2). PMID- 27685745 TI - Information exchange. AB - * I am working as an enrolled nurse on an intensive care unit. I plan to begin a follow-up bereavement service for patients' relatives. PMID- 27685746 TI - Gossip. AB - The health service is in a mess and it's all your fault...again. PMID- 27685747 TI - A Student's Dictionary of Psychology, 2nd edition A Student's Dictionary of Psychology, 2nd edition P Stratton N Hayes Edward Arnold 224pp L10.99 0-340-56926 3. AB - As suggested by the title, A Student's Dictionary of Psychology contains over 200 pages of definitions of terms and words used in psychology. PMID- 27685748 TI - When a baby dies N Kobner When a baby dies and A Henley SANDS/Pandora 256pp L6.99 0-04-440566-9. AB - It is difficult to recommend When a Baby Dies, an articulate and well-presented book, to anyone without great sadness that such a book should be necessary, that from every 100 established at least one family will need the advice and help it offers. The material discusses the incidence and trauma of a baby's death, particularly the parents' bewildered grief resulting from late miscarriage, stillbirth or after only a few weeks of their baby's life. PMID- 27685749 TI - Conflicts in Care Conflicts in Care L Mackey Chapman & Hall 298pp L13-95 0-412 47860-9 [Formula: see text]. AB - Four years ago, Lesley Mackay wrote a brilliant exposition on nursing and the problems it presented patients, managers, the government and themselves called Nursing a Problem (Milton Keynes, OUP). PMID- 27685750 TI - No fat spreadsheet. AB - This is another one of Borland's cut- down bargains. They are offering a smaller version of their well-known Quattro Pro spreadsheet program for less than L50. PMID- 27685751 TI - Listings. AB - August 6-8 An International Nurse Practitioners' Conference will be held at the cafe Royal, London. The organisers are Nursing Standard, and the Royal College of Nursing's Institute of Advanced Nursing Education and Community Nursing Association. Details from Karen Waterman, Nursing Standard, 17-19 Peterborough Road, Harrow, Middlesex HAL 2AX. Tel 081-423 1066. September 2-4 The RCN Society of Paediatric Nursing, inassociationwith Paediatric Nursing and Nursing Standard, will hold the first UK International Paediatric Nursing Conference at Churchill College, University of Cambridge. The theme is 'Commitment to care'. The fee is L2S0 for RCN members and L300 for non-members, excluding VAT. Details from Karen Waterman, Nursing Standard, Viking House, 17-19 Peterborough Road, Harrow HA1 2AX. Tel 081-423 1066. PMID- 27685752 TI - Editorial: Being responsive: promoting LGBTI health and well-being. PMID- 27685753 TI - Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI. AB - CONCLUSION: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. OBJECTIVE: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling. METHOD: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry. RESULTS: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule. PMID- 27685754 TI - Change in Quality of Life and Its Association with Oral Health and Other Factors in Community-Dwelling Elderly Adults-A Prospective Cohort Study. AB - OBJECTIVES: To determine whether changes in oral health status were associated with decline in quality of life (QoL). DESIGN: Prospective cohort study. SETTING: Carlos Barbosa, southern Brazil. PARTICIPANTS: A random sample of 872 community dwelling individuals aged 60 and older was evaluated in 2004. The current study population consisted of 389 participants available for follow-up in 2012. MEASURES: Change in QoL was assessed through the use of the short version of the World Health Organization QoL Assessment tool (WHOQOL-BREF) at baseline and follow-up. Each WHOQOL domain generates a score, with changes being calculated for each domain. Individuals with the same or higher scores at follow-up were categorized as having improved QoL, and those with lower scores were categorized as having a decline in QoL. Sociodemographic and health variables were assessed in an interview, and tooth loss, use of dental prostheses, and satisfaction with chewing ability and oral appearance were verified through oral examinations. Interviews and examinations were repeated. Risk ratios (RRs) relative to the outcome and independent variables were estimated using Poisson regression with a robust variance estimator. RESULTS: Tooth loss was a risk factor for decline in the psychological domain of QoL (RR = 1.04, 95% confidence interval (CI) = 1.02 1.06). Improvement in satisfaction with chewing ability was a protective factor for decline in this same domain (RR = 0.69, 95% CI = 0.50-0.97). Greater satisfaction with oral appearance was a protective factor against decline in social (RR = 0.84, 95% CI = 0.72-0.98) and environmental (RR = 0.77, 95% CI = 0.61-0.97) domain scores. CONCLUSION: Preventing tooth loss and recognizing and properly addressing concerns about chewing and dental appearance can affect the general well-being of community-dwelling elderly adults. PMID- 27685755 TI - Using visual guidance to retrain an experienced golfer's gaze: A case study. AB - Eye movements are essential for both predictive and reactive control of complex motor skills such as the golf swing. We examined the use of a visually guided learning protocol to retrain an experienced golfer's point-of-gaze immediately prior to execution of the full golf swing; his swing, and his gaze behaviour, had become established over more than a decade of practice and competition. Performance and eye movement data were obtained, from baseline, through intervention, to retention, for a total of 159 shots struck at a target 200 yards away. Results show that, at baseline, not only was the golfer's point-of-gaze not at the intended/predicted location, at the top-rear of the ball, but there was also high trial-to-trial variability. A bespoke visual guidance protocol improved his gaze behaviour considerably, in terms of accuracy and consistency - and this was reflected in accuracy and consistency of his shots. Implications of oculomotor interventions for the relearning of established motor skills are discussed. PMID- 27685756 TI - Crystal structure of beta1->6-galactosidase from Bifidobacterium bifidum S17: trimeric architecture, molecular determinants of the enzymatic activity and its inhibition by alpha-galactose. AB - : In a search for better comprehension of beta-galactosidase function and specificity, we solved the crystal structures of the GH42 beta-galactosidase BbgII from Bifidobacterium bifidum S17, a well-adapted probiotic microorganism from the human digestive tract, and its complex with d-alpha-galactose. BbgII is a three-domain molecule that forms barrel-shaped trimers in solution. BbgII interactions with d-alpha-galactose, a competitive inhibitor, showed a number of residues that are involved in the coordination of ligands. A combination of site directed mutagenesis of these amino acid residues with enzymatic activity measurements confirmed that Glu161 and Glu320 are fundamental for catalysis and their substitution by alanines led to catalytically inactive mutants. Mutation Asn160Ala resulted in a two orders of magnitude decrease of the enzyme kcat without significant modification in its Km , whereas mutations Tyr289Phe and His371Phe simultaneously decreased kcat and increased Km values. Enzymatic activity of Glu368Ala mutant was too low to be detected. Our docking and molecular dynamics simulations showed that the enzyme recognizes and tightly binds substrates with beta1->6 and beta1->3 bonds, while binding of the substrates with beta1->4 linkages is less favorable. DATABASE: Structural data are available in the PDB under the accession numbers 4UZS and 4UCF. PMID- 27685757 TI - HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV-based primary screening to liquid-based cytology for cervical cancer. AB - : Complete Round 1 data (baseline and 12-month follow-up) for HPV FOCAL, a randomized trial establishing the efficacy of HPV DNA testing with cytology triage as a primary screen for cervical cancer are presented. Women were randomized to one of three arms: Control arm - Baseline liquid-based cytology (LBC) with ASCUS results triaged with HPV testing; Intervention and Safety arms - Baseline HPV with LBC triage for HPV positives. Results are presented for 15,744 women allocated to the HPV (intervention and safety combined) and 9,408 to the control arms. For all age cohorts, the CIN3+ detection rate was higher in the HPV (7.5/1,000; 95%CI: 6.2, 8.9) compared to the control arm (4.6/1,000; 95%CI: 3.4, 6.2). The CIN2+ detection rates were also significantly higher in the HPV (16.5/1,000; 95%CI: 14.6, 18.6) vs. the control arm (10.1/1,000; 95%CI: 8.3, 12.4). In women >=35 years, the overall detection rates for CIN2+ and CIN3+ were higher in the HPV vs. the control arm (CIN2+:10.0/1,000 vs. 5.2/1,000; CIN3+: 4.2/1,000 vs. 2.2/1,000 respectively, with a statistically significant difference for CIN2+). HPV testing detected significantly more CIN2+ in women 25-29 compared to LBC (63.7/1,000; 95%CI: 51.9, 78.0 vs. 32.4/1,000; 95%CI: 22.3, 46.8). HPV testing resulted in significantly higher colposcopy referral rates for all age cohorts (HPV: 58.9/1,000; 95%CI: 55.4, 62.7 vs. CONTROL: 30.9/1,000; 95%CI: 27.6, 34.6). At completion of Round 1 HPV-based cervical cancer screening in a population-based program resulted in greater CIN2+ detection of across all age cohorts compared to LBC screening. PMID- 27685758 TI - Physician driven variation in the care of children with spinal muscular atrophy type 1. AB - BACKGROUND: Increasing numbers of families are requesting active supportive management for their child with spinal muscular atrophy type 1 (SMA1), leading to longer survival and greater prevalence of affected children. Strong opinions exist among physicians for and against the provision of care measures prolonging life. OBJECTIVE: To describe current practice in the care of SMA1 in Canada, and explore the factors underlying inter-physician variability. METHODS: A cross sectional survey of Canadian hospital-based pediatric neurologists and pediatric respirologists was performed in 2015. Odds ratios and 95% confidence intervals were calculated to compare proportions between groups. RESULTS: There was a 54% completion rate (99 physicians). Over half of participants believed that a disease modifying therapy was likely within 10 years. Quebec respirologists were 50 times less likely to offer long-term non-invasive ventilation (NIV) than respirologists in other provinces (OR 50.6, 95% CI 2.4-1075.3), and 20 times less likely to discuss tracheostomy with families (OR 20.4, 95% CI 2.0-211.8). High raters of perceived happiness of affected children were more likely to find NIV an acceptable measure for acute (OR 6.7, 95% CI 1.7-26.0) and chronic (OR 13.7, 95% CI 4.0-46.4) respiratory failure and prophylactic use (OR 5.8, 95% CI 2.2 15.6). CONCLUSION: Physician knowledge, opinions, subjective perception of child happiness, and regional factors, all influence physicians' practices and the shared decision-making process. Parents may not be informed or offered all the services available to their child. Knowledge translation initiatives are needed to enhance SMA1 care. Pediatr Pulmonol. 2017;52:662-668. (c) 2016 Wiley Periodicals, Inc. PMID- 27685759 TI - Towards a consensus on genotyping schemes for surveillance and outbreak investigations of Cryptosporidium, Berlin, June 2016. PMID- 27685760 TI - Domino Staudinger/aza-Wittig/Mannich Reaction: An Approach to Diversity of Di- and Tetrahydropyrrole Scaffolds. AB - A highly efficient and selective domino reaction producing valuable di- and tetrahydropyrrole-based skeletons from azidoethyl-substituted CH-acids and (thio)carbonyl compounds has been developed. By involving the additional functional groups in starting compounds into the domino reaction or postmodification of the primary reaction products, the simple construction of the pharmaceutically relevant three- and polycyclic azaheterocyclic scaffolds was demonstrated. PMID- 27685761 TI - Effect of Cortical Screw Diameter on Reduction and Stabilization of Type III Distal Phalanx Fractures: An Equine Cadaveric Study. AB - OBJECTIVE: To compare reduction of type III distal phalangeal fractures using 4.5 and 5.5 mm cortical screws placed in lag fashion and an intact hoof capsule model. STUDY DESIGN: Cadaveric experimental study. SAMPLE POPULATION: Hooves from 12 adult horses (n=24). METHODS: Sagittal fractures were created in pairs of distal phalanges after distal interphalangeal joint disarticulation and were reduced with either 4.5 or 5.5 mm cortical screws placed in lag fashion. Contralateral phalanges served as non-reduced controls. Fracture reduction following screw placement was assessed by comparing pre-reduction and post reduction fracture gap measurements from radiographs using paired t-tests. Effects of incremental loading (0, 135, 270, 540, 800, 1070, and 1335 kg) on fracture gaps in 6 phalanges reduced with 4.5 mm screws and 5 phalanges reduced with 5.5 mm screws were measured from fluoroscopic images and assessed by 2-way ANOVA. Significance was set at P<.05. RESULTS: Type III distal phalanx fractures were reliably created. Only 5.5 mm cortical screws, not 4.5 mm screws, significantly reduced fracture gaps and constrained fracture gap expansion 3 cm distal to the articular surface. Compressive loading closed the fracture gaps at the articular surface in both non-reduced control groups and those reduced with either 5.5 or 4.5 mm screws. CONCLUSION: The 5.5 mm cortical screws were more effective than 4.5 mm screws in reducing type III distal phalanx fractures and restricting distal fracture gap expansion under load. PMID- 27685762 TI - Drug induced interstitial lung disease in oncology phase I trials. AB - Interstitial lung disease is a serious drug-related condition that can cause life threatening organ failure. The incidence and risk factors of drug-induced interstitial lung disease (DILD) are unknown in oncology phase I trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled in 470 phase I trials sponsored by the Cancer Therapy Evaluation Program, National Cancer Institute, from 1988 to 2014. Logistic and Cox statistical analyses were utilized to determine clinical differences between patients who developed DILD and patients who did not. In this study, the overall incidence rate of patients with pulmonary toxicity was 2.7%. The overall incidence rate for DILD was 0.77%, whereas for grade 3 or 4 DILD it was 0.31%. Median time to occurrence of DILD was 1.4 months. The Cox hazard analysis indicated smaller body surface area and a combination of thoracic radiation with investigational drug regimens were significant risk factors for time to occurrence of interstitial lung disease. Investigators should carefully monitor for DILD in oncology patients enrolled in phase I trials with identified risk factors. A 6-month observation period would be sufficient to detect the onset of most DILD in such patients. PMID- 27685763 TI - How do relatives cope with eating disorders? Results from an Italian multicentre study. AB - OBJECTIVE: This paper aims to: (1) describe coping strategies in relatives of patients with eating disorders (EDs); (2) analyze coping strategies according to the different EDs; (3) identify correlations between patients' clinical characteristics, relatives' socio-demographic characteristics and coping strategies. METHODS: Patients and their relatives consecutively attending three outpatient units for EDs at the Universities of Naples SUN, Salerno and Catanzaro were recruited. Coping strategies were assessed through the Family Coping Questionnaire for Eating Disorders (FCQ-ED). It consists of 32 items, grouped into two factors: problem-oriented ("seek for information", "positive communication") and emotion-focused ("avoidance," "collusion," "coercion") strategies, plus one item on seeking for spiritual help. RESULTS: Seventy-two patients and 127 relatives were recruited. The most frequently reported coping strategies by relatives were seeking for information, positive communication, seeking for spiritual help; the first two coping strategies were positively correlated with the level of education of both patients and relatives. Mothers reported avoidance less frequently than other relatives. Relatives of patients with BN reported collusion and coercion more frequently compared to relatives of patients with AN. DISCUSSION: This report represents an initial attempt to understand the complex relationship among clinical, social and personal variables involved in the development of coping strategies. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:587-592). PMID- 27685764 TI - Emotional influences on perception and working memory. AB - Although there has been steady progress elucidating the influence of emotion on cognition, it remains unclear precisely when and why emotion impairs or facilitates cognition. The present study investigated the mechanisms involved in the influence of emotion on perception and working memory (WM), using modified 0 back and 2-back tasks, respectively. First, results showed that attentional focus modulated the impact of emotion on perception. Specifically, emotion facilitated perceptual task performance when it was relevant to the task, but it impaired performance when it was irrelevant to the task. The differential behavioural effect of emotion on perception as a function of attentional focus diminished under high WM load. Second, attentional focus did not directly modulate the impact of emotion on WM, but rather its influence depended on the dynamic relationship between internal representations. Specifically, WM performance was worse when the material already being held online and the new input were of matching emotions (e.g. both were negative), compared to when they were not. We propose that the competition between "bottom-up" and "top-down" processing for limited cognitive resources explains the nature of the influence of emotion on both perception and WM. PMID- 27685765 TI - Relationship between Widening and Position of the Tunnels and Clinical Results of Anterior Cruciate Ligament Reconstruction to Knee Osteoarthritis: 30 Patients at a Minimum Follow-Up of 10 Years. AB - To evaluate the relationship between tunnel position and widening and long-term clinical results in anterior cruciate ligament (ACL) reconstruction, a retrospective cohort of 30 patients undergoing ACL reconstruction with double semitendinous plus double gracilis (SAC technique) with longer than 10-year follow-up was selected. CT scans in the first 3 months and at final follow-up was evaluated. Position, angle, and widening of tunnels including Nebelung criteria were recorded in all CT scans. Physical, KT-1000, and clinical evaluation were performed at final follow-up. Outcomes and knee arthritis severity were evaluated at final follow-up. Mean follow-up was 11.2 +/- 1.2. At final follow-up, 85 and 57% of tibial and femoral tunnels, respectively, developed some degree of enlargement. Frontal tibial angle (mean) was 72 degrees , sagittal tibial angle 63 degrees , frontal femoral angle 47 degrees , sagittal femoral angle 20 degrees , and tunnels divergence angle 36 degrees . Preoperatively, KT-1000 30L and Lachman test scores were 5.52 and 5.79 respectively. In the last follow-up, 30L and manual Lachman test scores were 0.97 and 1.13, respectively (p < 0.001). In IKDC scale, pivot shift and Jerk tests showed 83 and 84% grade A results, respectively (p < 0.0001). In Fairbank scale, 23% worsened one grade and 27% worsened more than one grade (p < 0.005). Tibial tunnels widened more than femoral tunnels and further dilatation was found between intermediate and final follow-up. Higher incidence of tibial tunnel widening was observed in patients with tunnel verticalization. Tibial tunnel dilation was associated with long-term degenerative changes but not with final knee instability. PMID- 27685766 TI - The "Hoop" Plate for Posterior Bicondylar Shear Tibial Plateau Fractures: Description of a New Surgical Technique. AB - High-energy fractures of the proximal tibia with extensive fragmentation of the posterior rim of the tibial plateau are challenging. This technique aims to describe a method on how to embrace the posterior rim of the tibial plateau by placing a horizontal precontoured one-third tubular plate wrapped around its corners. This method, which we named "hoop plating," is mainly indicated for cases of crushed juxta-articular rim fractures, aiming to restore cortical containment of the tibial plateau. Through a lateral approach with a fibular head osteotomy (Lobenhoffer approach), both anterolateral and posterolateral fragments are directly reduced and supported by a one-third tubular plate of adequate length. The plate is inserted from lateral to medial deep to all soft tissues, and its position is checked with fluoroscopy. The implant sits exactly on the posterior cortex of the tibial plateau and provides containment for the reduced juxta-articular posterior cortex and rim. We begin with immediate range of motion. Toe-touch weight-bearing with crutches is allowed with the operated knee in full extension. Weight-bearing is gradually increased only after 6 weeks as bone healing is taking place. Clinical follow-up is performed at 1, 3, 6, and 12 weeks. If the radiological exam confirms that the fracture is healed, the patient is allowed to proceed to muscle strengthening and bear weight entirely. The "hoop plating" may be a good option for the management in cases of extensive posterior tibial plateau articular surface fracture and impaction with rim and posterior cortical wall fragmentation. PMID- 27685767 TI - Infrapatellar Fat Pad Excision during Total Knee Arthroplasty Did Not Alter the Patellar Tendon Length: A 5-Year Follow-Up Study. AB - Partial or total resection of the infrapatellar fat pad (IPFP) helps surgeon improve access to lateral tibial plateau for better placement of the knee prosthesis. We aimed to investigate the effect of IPFP excision on clinical and radiologic outcomes including patellar tendon length (PTL), range of motion, and functional scores after total knee arthroplasty (TKA) at 5-year follow-up. We retrospectively evaluated postoperative first X-rays (day 0) and postoperative final 5-year control views of 228 knees in patients with primary osteoarthritis who underwent TKA between September 2006 and December 2009 in our hospital. Exclusion criteria were patients who had lateral release, patellar resurfacing, septic or aseptic loosening, fracture around the replaced knee, any other prior knee surgery, or any systemic inflammatory disease. IPFP was completely resected in all knees to enhance surgical exposure and patellar mobilization. Radiologic evaluation of PTL was performed in early postoperative and 5-year control X-rays comparatively. The mean early postoperative PTL was 47.4 +/- 6 (range: 35-72), the mean final postoperative PTL was 47 +/- 6.3 (range: 33-68) (p = 0.1). The average preoperative flexion was 115 +/- 11 degrees, whereas it was 111 +/- 4 degrees, postoperatively (p = 0.73). Both the clinical and functional outcome scores improved in all patients. IPFP excision during TKA did not alter PTL at 5 year follow-up. A focus on other surgical and/or host-related factors may help clarify contradictory patellar tendon shortening reported in the literature. PMID- 27685768 TI - Evolving Beyond Craft Surgery Is Both Inevitable and Essential. AB - Given the increasing emphasis in health care on improving outcomes, reproducible results, and creating value for the patient, orthopedic surgery in particular must necessarily continue to progress away from an individualized and a surgeon specific technical craft and toward a highly automated and computer-integrated process in which surgeon and digitized systems interact to provide the most reproducible and consistent outcomes possible. In doing so, orthopedic surgery would follow the same path that every other highly reliable and safety conscious industry has adopted by absolute necessity. This evolution should therefore not be discouraged but rather embraced and accelerated. PMID- 27685769 TI - Aberrant changes of somatostatin and neuropeptide Y in brain of a genetic rat model for epilepsy: tremor rat. AB - Excessive excitation or loss of inhibitory neurotransmission has been closely related to epileptic activity. Somatostatin (SST) and Neuropeptide Y (NPY) are members of endogenous neuropeptides which are recognized as important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. Abnormal expression of these two neuropeptides evidenced in some epileptic models highlights the relevance of SST or NPY in the pathogenesis of epilepsy. The tremor rat (TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. The present study aimed to investigate the distribution and expression of SST and NPY in TRM brains, including hippocampus, temporal lobe cortex and cerebellum. Our RT-PCR data showed that up-regulated mRNA expression of SST and NPY was discovered in TRM hippocampus and temporal lobe cortex compared with control (Wistar) rats. The peptide levels of these neuropeptides in brain areas mentioned above were both apparently higher than that in normal Wistar rats as well. However, in cerebellums, neither SST nor NPY was significantly changed compared with control group. The immunohistochemical data showed that SST and NPY were widely present throughout CA1, CA3 and the hilus of hippocampus, the entorhinal cortex of temporal lobe cortex, as well as cerebellar Purkinje layer. In conclusion, our results discovered the aberrant changes of SST and NPY in several TRM brain regions, suggesting that the peptidergic system might be involved in TRM epileptiform activity. PMID- 27685770 TI - High-dose 1,25-dihydroxyvitamin D supplementation elongates the lifespan of Huntington's disease transgenic mice. AB - Huntington's disease is an autosomal dominant progressive neurodegenerative disease, which results in a decreased quality of life and an early death. A high prevalence of vitamin D deficiency was first described in a 2013 study in patients with manifest Huntington's disease, where serum vitamin D level was found to be associated with motor capabilities of the patients. Our objective was to investigate the effect of a high-dose vitamin D3 supplementation on a transgenic mouse model of Huntington's disease. Our study was performed on N171 82Q Huntington's disease transgenic mice in age- and gender-matched groups. We collected data on the motor state and survival of the mice. The results demonstrate that though vitamin D3 had no effect on the motor performance of transgenic mice, but significantly increased the lifespan of transgenic animals (Kaplan-Meier survival curves: vehicle-supplemented group: 73 (67-94) days vs. vitamin D3-supplemented group: 101 (74-109) days, p=0.048 Mantel-Cox log rank test). Further investigations are needed to determine whether a neuroprotective or a general corroborative effect of vitamin D leads to the measured effect. Our findings support the potential influence of vitamin D deficiency on the disease course and propose that vitamin D may be an effective supplementary treatment to beneficially influence clinical features of Huntington's disease. PMID- 27685771 TI - Effects of repetitive transcranial magnetic stimulation on non-veridical decision making. AB - We test the emerging hypothesis that prefrontal cortical mechanisms involved in non-veridical decision making do not overlap with those of veridical decision making. Healthy female subjects performed an experimental task assessing free choice, agent-centered decision making (The Cognitive Bias Task) and a veridical control task related to visuospatial working memory (the Moving Spot Task). Transcranial magnetic stimulation (TMS) was applied to the left and right dorsolateral prefrontal cortex (DLPFC) using 1 Hz and 10 Hz (intermittent) rTMS and sham protocols. Both 1 Hz and 10 Hz stimulation of the DLPFC triggered a shift towards a more context-independent, internal representations driven non veridical selection bias. A significantly reduced preference for choosing objects based on similarity was detected, following both 1 Hz and 10 Hz treatment of the right as well as 1 Hz rTMS of the left DLPFC. 1 Hz rTMS treatment of the right DLPFC also triggered a significant improvement in visuospatial working memory performance on the veridical task. The effects induced by prefrontal TMS mimicked those of posterior lesions, suggesting that prefrontal stimulation influenced neuronal activity in remote cortical regions interconnected with the stimulation site via longitudinal fasciculi. PMID- 27685772 TI - The effects of edaravone in ketamine-induced model of mania in rats. AB - Bipolar disorder is a chronic disease characterized by recurring episodes of mania and depression that can lead to disability. This study investigates the protective effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a drug with well-known antioxidant properties, in a model of mania induced by ketamine in rats. Locomotor activity was assessed in the open-field test. Superoxide dismutase (SOD), catalase (CAT) and thiobarbituric acid reactive substances (TBARS) levels were measured in order to evaluate oxidative damage in the rat hippocampus and prefrontal cortex. Increased locomotor activity (hyperlocomotion) was observed at the open-field test with ketamine treatment (25 mg/kg, i.p., 8 days). Edaravone (18 mg/kg) treatment did not prevent hyperlocomotion in the mania model induced with ketamine in rats, but lithium chloride (47.5 mg/kg, i.p., positive control) did prevent hyperlocomotion. Edaravone and lithium chloride treatments were found to reduce the increase in SOD and CAT activity following ketamine administration in a non-significant manner but caused no change in TBARS levels. PMID- 27685773 TI - Continuous MPTP intoxication in the Gottingen minipig results in chronic parkinsonian deficits. AB - Parkinson's disease (PD) is a common neurodegenerative disorder, resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Neuroprotective therapies in PD are still not available, perhaps because animal models do not imitate the chronic and progressive nature of the clinical state of PD. To address this, we performed a feasibility study aimed at establishing a chronic non-primate large animal PD model in Gottingen minipigs based on continuous infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). Twelve female Gottingen minipigs were divided into groups of 2-4 animals and implanted with infusion pumps for continuous intramuscular MPTP delivery of 4-24 mg MPTP/day for 11 weeks. The animals showed parkinsonian symptoms with bradykinesia, rigidity, coordination and chewing difficulties. Symptoms were stable in the 12 and 18 mg MPTP/day groups, whereas the remaining groups showed partial or full behavioral recovery. Digital gait analysis, high performance liquid chromatography (HPLC) measurements and stereological counts of tyrosine hydroxylase-positive (TH+) neurons in the SNc revealed a dose-related decrease in gait velocity, striatal metabolite levels and neuron numbers with increasing doses of MPTP. No neuronal inclusions were observed, but alpha-synuclein staining intensified with increased cumulative MPTP dosages. We conclude that this large-animal model of chronic MPTP administration in Gottingen minipigs shows trends of stable parkinsonian deficits at 18 mg MPTP/day in all modalities examined. This PD model shares many of the characteristics seen in patients and, although preliminary, holds considerable promise for future pre-clinical trials of neuroprotective therapies. PMID- 27685774 TI - Rat white matter injury model induced by endothelin-1 injection: technical modification and pathological evaluation. AB - White matter injury is an important cause of functional disability of the brain. We comprehensively analyzed a modified endothelin-1 (ET-1) injection-induced white matter injury model in the rat which is very valuable for investigating the underlying mechanisms of subcortical ischemic stroke. ET-1 was stereotactically injected into the internal capsule of the rat. To avoid complications with leakage of ET-1 into the lateral ventricle, the safest trajectory angle to the target was established. Rats with white matter injury were extensively evaluated for structural changes and functional sequelae, using motor function tests, magnetic resonance (MR) imaging, histopathology evolution, volume estimation of the lesion, and neuroanatomical identification of affected neurons using the retrograde tracer hydroxystilbamidine. Optimization of the trajectory of the ET-1 injection needle provided excellent survival rate. MR imaging visualized the white matter injury 2 days after surgery. Motor function deficit appeared temporarily after the operation. Histological studies confirmed damage of axons and myelin sheaths followed by inflammatory reaction and gliosis similar to lacunar infarction, with lesion volume of less than 1% of the whole brain. Hydroxystilbamidine injected into the lesion revealed wide spatial distribution of the affected neuronal population. Compared with prior ET-1 injection models, this method induced standardized amount of white matter damage and temporary motor function deficit in a reproducible and safe manner. The present model is valuable for studying the pathophysiology of not only ischemia, but a broader set of white matter damage conditions in the lissencephalic brain. PMID- 27685775 TI - Effects of social stress and clomipramine on emotional memory in mice. AB - We have previously observed impairing effects of social defeat stress (CSDS) on inhibitory avoidance (IA) in mice. Given the similarity between changes produced by social stress in animals and symptoms of certain human psychopathologies such as depression and anxiety, the effects of the antidepressant clomipramine on IA impairment produced by CSDS were evaluated in the present study. Male CD1 mice were randomly assigned to the groups: non-stressed+saline, non stressed+clomipramine, stressed+saline and stressed+clomipramine. Stressed animals were subjected to daily agonistic encounters (10 min) in the home cage of the aggressor over a 20-day period. Just before each encounter, non-stressed and stressed mice were injected i.p. with saline or clomipramine (10 mg/kg) according to their experimental condition. 24 hours after the last CSDS session, all the mice were tested in a step-through IA task. In the IA training phase, animals were punished by a shock to the paw when they entered the dark compartment of the apparatus. In the IA test phase (one week later) the same procedure took place, but without shock. Complementary measures were obtained by evaluating all the animals in an elevated plus maze (locomotor activity and emotionality) and on a hot plate (analgesia). IA learning was confirmed in all groups except the stressed+saline group, which was the only one that exhibited higher anxiety levels. No variations were observed in either locomotor activity or analgesia. In conclusion, CSDS induces anxiety and impairs emotional memory in mice; the negative effects of CSDS on memory appear to be attenuated by clomipramine, and these detrimental effects do not seem to be secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity. PMID- 27685777 TI - Spatial memory formation differentially affects c-Fos expression in retrosplenial areas during place avoidance training in rats. AB - The retrosplenial cortex is involved in spatial memory function, but the contribution of its individual areas is not well known. To elucidate the involvement of retrosplenial cortical areas 29c and 30 in spatial memory, we analyzed the expression of c-Fos in these areas in the experimental group of rats that were trained in a spatial place avoidance task, i.e. to avoid shocks presented in an unmarked sector of a stable arena under light conditions. Control rats were trained in the same context as the experimental rats either without (Control-noUS) or with shocks (Control-US) that were delivered in a random, noncontingent manner for three days. On the first day of place avoidance learning, the experimental group exhibited c-Fos induction in area 29c, similar to both control groups. In area 30, similarly high levels of c-Fos expression were observed in the experimental and Control-US groups. On the third day of training, when the experimental group efficiently avoided c-Fos expression in areas 29c and 30 was lower compared with the first day of training. In area 29c c Fos level was also lower in the experimental than in comparison to the Control-US group. In area 30, c-Fos expression in the experimental group was lower than in both control groups. In conclusion, areas 29c and 30 appear to be activated during spatial memory acquisition on the first day of training, whereas area 30 seems suppressed during long-term memory functioning on the third day of training when rats effectively avoid. PMID- 27685776 TI - The false-positive responses of analgesic drugs to the intradermal serotonin- and compound 48/80-induced scratches as an animal model of itch. AB - Intradermal injection of pruritogens such as serotonin, histamine and compound 48/80 into the skin and then, the evaluation of the scratching behavior is the commonly used animal model to advance pruritic research and drug development. However, predictive validity of this model is poorly documented. There is a close interaction between itch and pain sensations with regard to mediation through an anatomically and functionally identical neuronal pathway. One approach is whether the existing animal model of itch differentiates itch or pain to show efficacy of clinically effective analgesic drugs as a back translation. In this study, we explored the effects of different group of analgesic drugs on serotonin and compound 48/80-induced scratching behavior in Balb-C mice. Serotonin (25 MUg) and compound 48/80 (100 MUg) was injected intradermally in a volume of 50 MUl into the rostral part of skin on the back of male mice and scratches were counted for a 30-min observation period. Morphine (1, 3, 10 mg/kg), tramadol (20, 40, 80 mg/kg), cannabinoid agonist CP 55,940 (0.1, 0.3, 1 mg/kg), paracetamol (100, 200, 300 mg/kg) and diclofenac (50, 100, 200 mg/kg) were given intraperitoneally 30 min prior to pruritogen injection. The analgesic drugs dose dependently blocked serotonin and compound 48/80-induced straching behavior with exerting complete inhibition at certain doses. Our data suggests that intradermal pruritogen induced scratching models may not discriminate pain and itch sensations and give false positive results when standard analgesic drugs are used. PMID- 27685778 TI - An anatomical study of the transversus nuchae muscle: Application to better understanding occipital neuralgia. AB - The transversus nuchae muscle appears inconsistently in the occipital region. It has gained attention as one of the muscles composing the superficial musculoaponeurotic system (SMAS). The purpose of this study was to clarify its detailed anatomical features. We examined 124 sides of 62 cadavers. The transversus nuchae muscle was identified when present and examined after it had been completely exposed. We also examined its relationship to the occipital cutaneous nerves.The transversus nuchae muscle was detected in 40 sides (40/124, 32.2%) of 26 cadavers; it was present bilaterally in 14 and unilaterally in 12. It originated from the external occipital protuberance; 43% of the observed muscles inserted around the mastoid process, and 58% curved upward around the mastoid process and became the uppermost bundle of the platysma. In one case, an additional bundle originated from the lower posterior border of the sternocleidomastoid muscle and coursed obliquely upward along with platysma. Ninety percent of the muscles ran below the sling through which the greater occipital nerve passed; 65% of the lesser occipital nerves ran deep to the muscle, and 55% of the great auricular nerves ran superficial to it. Our observations clarify the unique anatomical features of the transversus nuchae muscle. We found that it occurs at a rate similar to that described in previous reports, but its arrangement is variable. Further investigations will be performed to clarify its innervation and other anatomical features. Clin. Anat. 30:32-38, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27685779 TI - A framework for cumulative risk assessment in the 21st century. AB - The ILSI Health and Environmental Sciences Institute (HESI) has developed a framework to support a transition in the way in which information for chemical risk assessment is obtained and used (RISK21). The approach is based on detailed problem formulation, where exposure drives the data acquisition process in order to enable informed decision-making on human health safety as soon as sufficient evidence is available. Information is evaluated in a transparent and consistent way with the aim of optimizing available resources. In the context of risk assessment, cumulative risk assessment (CRA) poses additional problems and questions that can be addressed using the RISK21 approach. The focus in CRA to date has generally been on chemicals that have common mechanisms of action. Recently, concern has also been expressed about chemicals acting on multiple pathways that lead to a common health outcome, and non-chemical other conditions (non-chemical stressors) that can lead to or modify a common outcome. Acknowledging that CRAs, as described above, are more conceptually, methodologically and computationally complex than traditional single-stressor risk assessments, RISK21 further developed the framework for implementation of workable processes and procedures for conducting assessments of combined effects from exposure to multiple chemicals and non-chemical stressors. As part of the problem formulation process, this evidence-based framework allows the identification of the circumstances in which it is appropriate to conduct a CRA for a group of compounds. A tiered approach is then proposed, where additional chemical stressors and/or non-chemical modulating factors (ModFs) are considered sequentially. Criteria are provided to facilitate the decision on whether or not to include ModFs in the formal quantitative assessment, with the intention to help focus the use of available resources to have the greatest potential to protect public health. PMID- 27685780 TI - Culture, myths and panic: Three decades and beyond with an HIV/AIDS epidemic in Zimbabwe. AB - Zimbabwe is going through a generalised acquired immunodeficiency syndrome (AIDS) epidemic. The first five years of the epidemic (1985-1990) were characterised by lack of medicines against human immunodeficiency virus (HIV), and an exponential increase in prevalence (65-fold) and incidence (13-fold), which were fuelled by high-risk sexual behaviour. The high HIV prevalence, mortality and stigma yielded great fear and panic in the population, which are thought to have led to confusion and hopelessness, and, in turn, increased risky sexual behaviour. The country's government and civil society embarked on HIV awareness campaigns that are claimed to have played a central role in slowing down the epidemic since the mid-2000s. HIV-related mortality then fell by 70% between 2003 and 2013, which is attributed to high uptake of antiretroviral therapy (ART) and prevention of mother-to-child transmission (95%) prophylaxis. However, the epidemic has been characterised by a low paediatric ART coverage (35% in 2011 to 46.12% in 2013). Year 2014 saw an increase in adolescent and young adult HIV prevalence, which may be signalling a rebound of the epidemic. A more holistic approach which deals with the epidemic in its socio-political context is required to effectively lower the country's HIV burden. PMID- 27685781 TI - Assessment of the interaction procedure between Pt(IV) prodrug [Pt(5,5'-dmbpy)Cl4 and human serum albumin: Combination of spectroscopic and molecular modeling technique. AB - In this study, a cytotoxic Pt(IV) complex [Pt(5,5'-dmbpy)Cl4 (5,5'-dmbpy is 5,5' dimethyl-2,2'-bipyridine) was selected to investigate its affinity to human serum albumin (HSA) by spectroscopy and molecular docking methods. This complex has a bidentate nitrogen donor ligand with four chloride anions attached to a Pt(IV) metal in a distorted octahedral environment. The fluorescence data showed this complex quench the intrinsic fluorescence of HSA through a static quenching mechanism. The binding constant (Kb) and the number of binding sites (n) were obtained based on the results of fluorescence measurements. UV-vis, circular dichroism spectroscopy, and three-dimensional fluorescence spectroscopy proved that the Pt(IV) complex could slightly change the secondary structure of protein. Thermodynamic parameters show that the Pt(IV) complex binds to HSA through electrostatic and Vander Waals interactions with one binding site. The molecular docking results confirmed the spectroscopic results and showed that Pt(IV) complex is embedded into subdomain IIA of protein. The aim of this study is to describe the performance of effective anti-cancer drugs when faced with proteins such as HSA. PMID- 27685782 TI - Continuous up to 4 Years Entecavir Treatment of HBV-Infected Adolescents - A Longitudinal Study in Real Life. AB - This study evaluated the long-term (up to 4 years) efficacy and safety of entecavir ETV treatment and analysed the significance of baseline and on treatment factors in long-term ETV outcomes in adolescents with chronic hepatitis B (CHB). We determined the cumulative virological and serological outcomes of 44 adolescents with CHB receiving ETV for up to 4 years. To investigate the dynamics of HBV DNA, ALT activity and hepatitis B e antigen (HBeAg) seroconversion over time and their associations with the considered factors, generalized estimating equation (GEE) models were used. The cumulative rates of undetectable HBV DNA (<20 IU/ml) and HBeAg seroconversion after 4 years were 89.7% and 55.4%, respectively. In the study group, we showed that having undetectable HBV DNA at the 6th or 12th month of therapy predicted the achievement of a sustained response rate (SRR, defined as the loss of HBV DNA, loss of HBeAg and ALT normalization) at year 3 of ETV therapy (P = 0.048, OR = 5.83; P = 0.012; OR = 14.57, respectively). The GEE analysis indicated that of the different factors, the duration of ETV therapy had a strong impact on the achievement of virological suppression, HBeAg seroconversion and SRR in adolescents. Each month after the initiation of therapy, the odds of loss of HBV DNA increased by approximately 5% (OR = 1.05, P<0.0001), on average. Additionally, the GEE analysis revealed that adolescents with an age at infection of >=10 years had 3 times higher odds of achieving undetectable HBV DNA than patients with a younger infection age (OR = 3.67, P = 0.028). None of the ETV-treated patients reported significant adverse effects. ETV is an effective and safe treatment option for adolescents with CHB. Undetectable HBV DNA in the 6th and/or 12th month of ETV treatment and older age at infection could predict maintained virological suppression. PMID- 27685783 TI - Operating Characteristics of a Tuberculosis Screening Tool for People Living with HIV in Out-Patient HIV Care and Treatment Services, Rwanda. AB - BACKGROUND: The World Health Organization (WHO) 2010 guidelines for intensified tuberculosis (TB) case finding (ICF) among people living with HIV (PLHIV) includes a recommendation that PLHIV receive routine TB screening. Since 2005, the Rwandan Ministry of Health has been using a five-question screening tool. Our study objective was to assess the operating characteristics of the tool designed to identify PLHIV with presumptive TB as measured against a composite reference standard, including bacteriologically confirmed TB. METHODS: In a cross-sectional study, the TB screening tool was routinely administered at enrolment in outpatient HIV care and treatment services at seven public health facilities. From March to September 2011, study enrollees were examined for TB disease irrespective of TB screening outcome. The examination consisted of a chest radiograph (CXR), three sputum smears (SS), sputum culture (SC) and polymerase chain reaction line-probe assay (Hain test). PLHIV were classified as having "laboratory-confirmed TB" with positive results on SS for acid-fast bacilli, SC on Lowenstein-Jensen medium, or a Hain test. RESULTS: Overall, 1,767 patients were enrolled and screened of which; 1,017 (57.6%) were female, median age was 33 (IQR, 27-41), and median CD4+ cell count was 385 (IQR, 229-563) cells/mm3. Of the patients screened, 138 (7.8%) were diagnosed with TB of which; 125 (90.5%) were laboratory-confirmed pulmonary TB. Of 404 (22.9%) patients who screened positive and 1,363 (77.1%) who screened negative, 79 (19.5%) and 59 (4.3%), respectively, were diagnosed with TB. For laboratory-confirmed TB, the tool had a sensitivity of 54.4% (95% CI 45.3-63.3), specificity of 79.5% (95% CI 77.5-81.5), PPV of 16.8% and NPV of 95.8%. CONCLUSION: TB prevalence among PLHIV newly enrolling into HIV care and treatment was 65 times greater than the overall population prevalence. However, the performance of the tool was poorer than the predicted performance of the WHO recommended TB screening questions. PMID- 27685784 TI - Intrusive Memories of Distressing Information: An fMRI Study. AB - Although intrusive memories are characteristic of many psychological disorders, the neurobiological underpinning of these involuntary recollections are largely unknown. In this study we used functional magentic resonance imaging (fMRI) to identify the neural networks associated with encoding of negative stimuli that are subsequently experienced as intrusive memories. Healthy partipants (N = 42) viewed negative and neutral images during a visual/verbal processing task in an fMRI context. Two days later they were assessed on the Impact of Event Scale for occurrence of intrusive memories of the encoded images. A sub-group of participants who reported significant intrusions (n = 13) demonstrated stronger activation in the amygdala, bilateral ACC and parahippocampal gyrus during verbal encoding relative to a group who reported no intrusions (n = 13). Within-group analyses also revealed that the high intrusion group showed greater activity in the dorsomedial (dmPFC) and dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus and occipital regions during negative verbal processing compared to neutral verbal processing. These results do not accord with models of intrusions that emphasise visual processing of information at encoding but are consistent with models that highlight the role of inhibitory and suppression processes in the formation of subsequent intrusive memories. PMID- 27685785 TI - Bisphenol A and Bisphenol S Induce Distinct Transcriptional Profiles in Differentiating Human Primary Preadipocytes. AB - Bisphenol S (BPS) is increasingly used as a replacement plasticizer for bisphenol A (BPA) but its effects on human health have not been thoroughly examined. Recent evidence indicates that both BPA and BPS induce adipogenesis, although the mechanisms leading to this effect are unclear. In an effort to identify common and distinct mechanisms of action in inducing adipogenesis, transcriptional profiles of differentiating human preadipocytes exposed to BPA or BPS were compared. Human subcutaneous primary preadipocytes were differentiated in the presence of either 25 MUM BPA or BPS for 2 and 4 days. Poly-A RNA-sequencing was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. BPA-treatment resulted in 472 and 176 DEGs on days 2 and 4, respectively, affecting pathways such as liver X receptor (LXR)/retinoid X receptor (RXR) activation, hepatic fibrosis and cholestasis. BPS-treatment resulted in 195 and 51 DEGs on days 2 and 4, respectively, revealing enrichment of genes associated with adipogenesis and lipid metabolism including the adipogenesis pathway and cholesterol biosynthesis. Interestingly, the transcription repressor N-CoR was identified as a negative upstream regulator in both BPA- and BPS-treated cells. This study presents the first comparison of BPA- and BPS-induced transcriptional profiles in human differentiating preadipocytes. While we previously showed that BPA and BPS both induce adipogenesis, the results from this study show that BPS affects adipose specific transcriptional changes earlier than BPA, and alters the expression of genes specifically related to adipogenesis and lipid metabolism. The findings provide insight into potential BPS and BPA-mediated mechanisms of action in inducing adipogenesis in human primary preadipocytes. PMID- 27685786 TI - Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review. AB - Glucocorticoid-induced postmenopausal osteoporosis is a severe osteoporosis, with high risk of major osteoporotic fractures. This severe osteoporosis urges more extensive and deeper basic study, in which suitable animal models are indispensable. However, no relevant review is available introducing this model systematically. Based on the recent studies on GI-PMOP, this brief review introduces the GI-PMOP animal model in terms of its establishment, evaluation of bone mass and discuss its molecular mechanism. Rat, rabbit and sheep with their respective merits were chosen. Both direct and indirect evaluation of bone mass help to understand the bone metabolism under different intervention. The crucial signaling pathways, miRNAs, osteogenic- or adipogenic- related factors and estrogen level may be the predominant contributors to the development of glucocorticoid-induced postmenopausal osteoporosis. PMID- 27685787 TI - Decitabine and 5-azacitidine both alleviate LPS induced ARDS through anti inflammatory/antioxidant activity and protection of glycocalyx and inhibition of MAPK pathways in mice. AB - Decitabine (5-aza-2'-deoxycytidine, DAC) and 5-azacitidine (Aza), an inhibitor of DNA methyltransferases, possess a wide range of anti-metabolic and anti-cancer activities. This study examined the effects of DAC and Aza on inflammatory and oxidative injuries, as well as on glycocalyx and MAPK signaling pathways, in a LPS-stimulated ARDS mouse model. Results of ELISA revealed that DAC and Aza significantly inhibited the production of TNF-alpha and IL-1beta and prevented LPS-induced elevation of myeloperoxidase and malondialdehyde levels in serum. The W/D ratio of lung and histopathologic examination with hematoxylin and eosin staining showed that DAC and Aza pretreatment substantially improved lung tissue injury. DAC and Aza reduced the level of glycocalyx degradation products (e.g., heparan sulfate and haluronic acid) and protected glycocalyx integrity. Western blot assay demonstrated that DAC and Aza both significantly suppressed LPS induced activation of the MAPK signaling pathways by blocking the phosphorylation of JNK, ERK and P38 in lung tissues. Bisulfite sequencing PCR and real time-PCR showed that DAC reversed the RASSF1A promoter hypermethylation and furthermore elevated the expression of RASSF1A, which is a tumor suppressor that regulates MAPK signaling pathway. These results suggested that DAC inhibited the MAPK signaling pathway in LPS-induced ARDS mice might via demethylation in RASSF1A promoter region and by restoring its expression. This study highlighted the close relationship between DNA methylation and the development and progression of ARDS. PMID- 27685788 TI - Enhancement of orofacial antinociceptive effect of carvacrol, a monoterpene present in oregano and thyme oils, by beta-cyclodextrin inclusion complex in mice. AB - Orofacial pain is associated with diagnosis of chronic pain of head, face, mouth, neck and all the intraoral structures. Carvacrol, a naturally occurring isoprenoid with diverse class of biological activities including anti inflammatory, analgesic, antitumor and antioxidant properties. Now, the antinociceptive effect was studied in mice pretreatment with carvacrol (CARV) and beta-cyclodextrin complex containing carvacrol (CARV-betaCD) in formalin-, capsaicin-, and glutamate- induced orofacial nociception. Mice were pretreated with vehicle (0.9% Nacl, p.o.), CARV (10 and 20mg/kg, p.o.), CARV-betaCD (10 and 20mg/kg, p.o.) or MOR (10mg/kg, i.p.) before the nociceptive behavior induced by subcutaneous injections (s.c.) of formalin (20MUl, 2%), capsaicin (20MUl, 2.5MUg) or glutamate (20MUl, 25MUM) into the upper lip respectively. The interference on motor coordination was determined using rotarod and grip strength meter apparatus. CARV-betaCD reduced the nociceptive during the two phases of the formalin test, whereas CARV did not produced the reduction in face-rubbing behavior in the initial phase. CARV-betaCD (20mg/kg, p.o.) produced 49.3% behavior pain while CARV alone at 20mg/kg, p.o, produced 28.7% of analgesic inhibition in the second phase of formalin test. CARV, CARV-betaCD and Morphine (MOR) showed a significant reduction against nociception caused by capsaicin or glutamate injection. Thus the encapsulation of carvacrol in beta-cyclodextrin can acts as a considerable therapeutic agent with pharmacological interest for the orofacial pain management. PMID- 27685789 TI - FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways. AB - Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). Romidepsin (FK228), a histone deacetylase inhibitor, is a promising new class of antineoplastic agent with the capacity to induce growth arrest and/or apoptosis of cancer cells. However, combination of the two drugs in glioma remains largely unknown. In the present study, we evaluated the combinatory effects of FK228 with TMZ in glioma, and its molecular mechanisms responsible for these effects. Glioma cell lines were treated with TMZ, FK228 or the combination of drugs. The resistance effect including cytotoxicity and apoptosis was determined in glioma cells, respectively. We further evaluated the effects of FK228 in the PI3K/Akt-signaling pathway in vitro. Mice engrafted with 5*106 LN382 cells were treated with TMZ, FK228 or the combination of two drugs, and tumor weights and volumes were measured, respectively. FK228 enhanced the cytotoxic effects of TMZ in glioma cells compared to vehicle-treated controls or each drug alone. The combination of FK228 and TMZ-induced apoptosis was demonstrated by increased expression of cleaved Caspase 3, Bax, cleaved-PARP, and decreased Bcl-2 expression. Furthermore, the expression of key components of the PI3K/Akt-signaling pathway showed that combination of FK228 and TMZ block PI3K/Akt pathways in vitro. This block effect was also confirmed in vivo in mice models. Mice treated with both FK228 and TMZ drugs showed significantly reduced tumor weights and volumes, compared to each drug alone. Our results suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ resistant gliomas, although further studies will be needed. PMID- 27685790 TI - The influence of lipoic acid on caveolin-1-regulated antioxidative enzymes in the mouse model of acute ulcerative colitis. AB - AIM: This study was undertaken to verify if two-weeks treatment of lipoic acid (LA) influence colon damage and pro-inflammatory cytokine synthesis during DSS induced acute colitis. Moreover, as LA has anti-oxidative properties, we analyzed its influence on the level of antioxidative enzymes, HO-1 and eNOS, and their regulator- caveolin-1. METHODS: LA was administrated to male C57/BALBc mice at a dose of 25 or 50mg/kg/day (i.p.) for 21days. Acute colitis was induced by administration of 4% DSS (w/v) in drinking water for 5days, followed by 2days of normal drinking water. Mice in LA+DSS groups were treated with LA (25 or 50mg/kg/day; i.p.) starting 14days prior to 4% DSS. Control group received saline for 21days. In the colon tissue we measured myeloperoxidase activity (MPO), IL 1beta, IL-6, IL-17A, IL-23 (ELISA method), and tissue level of cav-1, phospho eNOS, total eNOS and HO-1 (Western blot). RESULTS: Administration of DSS significantly increased total colon damage (p<0.001), myeloperoxidase (MPO) activity (p<0.05) and pro-inflammatory IL-6 (p<0.05). There was also a tendency towards higher IL-1beta, IL-17A, and IL-23 in the colon. LA alone did not influence total colon damage, MPO activity, and pro-inflammatory cytokines concentration compared to control (p<0.05). Notably, mice treated with LA and DSS had significantly decreased total colon damage score (p<0.001), despite augmented colon MPO activity (p<0.01), but similar (IL-17A) or even significantly higher level (IL-1beta, IL-23) as compared to the DSS group (p<0.05). IL-6 was insignificantly decreased after LA treatment at a dose of 50mg/kg. In acute colitis there was a tendency towards an increase in cav-1 and HO-1 and a decrease p-eNOS/total eNOS ratio. Moreover, the LA+DSS groups had higher expression of HO 1 and p-eNOS/total eNOS (p<0.05) compared to the DSS group, and a tendency towards higher cav-1 level. The changes did not depend on LA dose. CONCLUSION: Our study indicated that LA, at lower doses, may influence cav-1-regulated antioxidative enzyme levels (HO-1 and p-eNOS/total eNOS) despite an increase in colon pro-inflammatory cytokine levels during acute colitis. Hence, LA treatment may be - to some extent - beneficial in attenuation of acute colitis. PMID- 27685791 TI - Anti-Trichomonas vaginalis activity of betulinic acid derivatives. AB - Caused by Trichomonas vaginalis, trichomoniasis is the most common non-viral STD worldwide. Currently, metronidazole and tinidazole are the only drugs approved for treatment of the condition. However, problems such as metronidazole-resistant T. vaginalis isolates and allergic reactions have been reported. Based on data previously published by our group, structural changes in betulinic acid (1) were performed, generating three new compounds that were tested for in vitro anti T.vaginalis activity in this study. Whereas derivative 2 did not demonstrate anti T. vaginalis activity, derivatives 3 and 4 reduced trophozoite viability by 100%, with MIC values of 50MUM. The structural difference of two compounds was performed only on the C-28 position. Derivative 3 showed low cytotoxicity against Vero cells in 24h; however, derivative 4 was highly cytotoxic, but efficient when associated with metronidazole in the synergism assay. ROS production by neutrophils was reduced, and derivative 3 showed anti-inflammatory effect. Collectively, the results of this study provide in vitro evidence that betulinic acid derivatives 3 and 4 are potential compounds with anti-T. vaginalis activity. PMID- 27685792 TI - Functionalized nanosponges for controlled antibacterial and antihypocalcemic actions. AB - The aim of the present work was to develop lysozyme impregnated surface-active nanosponges to maintain its conformational stability and break bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetyl-d glucosamine and N-acetylmuramic acid residues present in peptidoglycan layer surrounding the bacterial cell membrane, and for controlling the release of calcium in hypocalcemia condition. Different carbonyl diimidazole cross-linked beta-cyclodextrin nanosponges with and without CaCO3 and CMC were prepared by polymer condensation method. The surface-active nanosponges were impregnated by lysozyme due to their ability to adsorb protein. Lysozyme impregnated nanosponges had a monomodal particle size distribution of 347.46+/-3.07 to 550.34+/-5.23nm, with a narrow distribution. The zeta potentials were sufficiently increased upon lysozyme impregnation, suggesting stable formulations by preventing aggregation. The in vitro release studies showed controlled release of lysozyme and calcium over a period of 24h. FTIR studies confirmed the impregnation of lysozyme on nanosponges and encapsulation of calcium in nanosponges. Lysozyme formulation showed promising conformational stability by DSC. It can be concluded that the stable nanosponges formulation is a promising carrier for antibacterial protein and preventing depletion of calcium in antibiotic associated hypocalcemic condition. PMID- 27685794 TI - In vitro and in vivo inhibition of aldose reductase and advanced glycation end products by phloretin, epigallocatechin 3-gallate and [6]-gingerol. AB - Hyperglycemic stress activates polyol pathway and aldose reductase (AR) key enzyme responsible for generating secondary complications during diabetes. In this study the therapeutic potential of phloretin, epigallocatechin 3-gallate (EGCG) and [6]-gingerol were evaluated for anti-glycating and AR inhibitory activity in vitro and in vivo systems. Human retinal pigment epithelial (HRPE) cells were induced with high glucose supplemented with the phloretin, EGCG and [6]-gingerol. Aldose reductase activity, total advanced glycation end products (AGEs) and enzyme inhibitor kinetics were assessed. Male C57BL/6J mice were randomly assigned to one of the different treatments (bioactive compounds at 2 concentrations each) with either a low fat diet or high fat diet (HFD). After sixteen weeks, AGE accumulation and AR activity was determined in heart, eyes and kidney. High glucose induced toxicity decreased cell viability compared to the untreated cells and AR activity increased to 2-5 folds from 24 to 96h. Pre treatment of cells with phloretin, EGCG and [6]-gingerol improved cell viability and inhibited AR activity. The enzyme inhibition kinetics followed a non competitive mode of inhibition for phloretin and EGCG whereas [6]-gingerol indicated uncompetitive type of inhibition against AR. Data from the animal studies showed high plasma glucose levels in HFD group over time, compared to the low fat diet. HFD group developed cataract and AR activity increased to 4 folds compared to the group with low fat diet. Administration of EGCG, phloretin and [6]-gingerol significantly reduced blood sugar levels, AGEs accumulation, and AR activity. These findings could provide a basis to consider using the selected dietary components alone or in combination with other therapeutic approaches to prevent diabetes-related complications in humans. PMID- 27685793 TI - TAK-242 treatment ameliorates liver ischemia/reperfusion injury by inhibiting TLR4 signaling pathway in a swine model of Maastricht-category-III cardiac death. AB - OBJECTIVES: This study aims to test the effects of TAK-242 on liver transplant viability in a model of swine Maastricht-category-III cardiac death. METHODS: A swine DCD Maastricht-III model of cardiac death was established, and TAK-242 was administered prior to the induction of cardiac death. The protein and mRNA level of TLR4 signaling pathway molecules and cytokines that are important in mediating immune and inflammatory responses were assessed at different time points following the induction of cardiac death. RESULTS: After induction of cardiac death, both the mRNA and protein levels of key molecules (TLR4, TRAF6, NF-kappaB, ICAM-1, MCP-1 and MPO), TNF-alpha and IL-6 increased significantly. Infusion of TAK-242 1h before induction of cardiac death blocked the increase of immune and inflammatory response molecules. However, the increase of TLR4 level was not affected by infusion of TAK-242. Histology study showed that infusion of TAK-242 protect liver tissue from damage during cardiac death. CONCLUSIONS: These results indicates that TLR4 signaling pathway may contribute to ischemia/reperfusion injury in the liver grafts, and blocking TLR4 pathway with TAk-242 may reduce TLR4-mediated tissue damage. PMID- 27685797 TI - Day surgery regional anesthesia in children: safety and improving outcomes, do they make a difference? AB - PURPOSE OF REVIEW: The objective of this review is to provide an overview of recent developments in pediatric regional anesthesia and elucidate outcomes as it relates to patient safety and overall satisfaction. RECENT FINDINGS: Since the inception of the Pediatric Regional Anesthesia Network database, the acquisition of data has enabled the pediatric anesthesiologist to extrapolate results and translate them into useful outcomes. Despite the growing trend to provide regional anesthesia in the pediatric population, there continues to be a paucity of available research studies to evaluate outcomes of various regional nerve blocks. This review serves as a conduit to explore the most recent data available, in each regional anesthetic technique, as it relates to outcomes such as analgesia, patient safety and satisfaction. SUMMARY: Despite the limited number of randomized controlled trials evaluating the safety of individual regional anesthetic techniques, the growing body of data, such as presented in the Pediatric Regional Anesthesia Network database, suggests a high degree of safety in performing various regional anesthetic modalities. Modern medicine should continue to embrace the use of regional anesthesia, particularly in the ambulatory setting, to reduce perioperative pain and improve patient outcomes. PMID- 27685796 TI - Insights into the Utility of the Focal Adhesion Scaffolding Proteins in the Anaerobic Fungus Orpinomyces sp. C1A. AB - Focal adhesions (FAs) are large eukaryotic multiprotein complexes that are present in all metazoan cells and function as stable sites of tight adhesion between the extracellular matrix (ECM) and the cell's cytoskeleton. FAs consist of anchor membrane protein (integrins), scaffolding proteins (e.g. alpha-actinin, talin, paxillin, and vinculin), signaling proteins of the IPP complex (e.g. integrin-linked kinase, alpha-parvin, and PINCH), and signaling kinases (e.g. focal adhesion kinase (FAK) and Src kinase). While genes encoding complete focal adhesion machineries are present in genomes of all multicellular Metazoa; incomplete machineries were identified in the genomes of multiple non-metazoan unicellular Holozoa, basal fungal lineages, and amoebozoan representatives. Since a complete FA machinery is required for functioning, the putative role, if any, of these incomplete FA machineries is currently unclear. We sought to examine the expression patterns of FA-associated genes in the anaerobic basal fungal isolate Orpinomyces sp. strain C1A under different growth conditions and at different developmental stages. Strain C1A lacks clear homologues of integrin, and the two signaling kinases FAK and Src, but encodes for all scaffolding proteins, and the IPP complex proteins. We developed a protocol for synchronizing growth of C1A cultures, allowing for the collection and mRNA extraction from flagellated spores, encysted germinating spores, active zoosporangia, and late inactive sporangia of strain C1A. We demonstrate that the genes encoding the FA scaffolding proteins alpha-actinin, talin, paxillin, and vinculin are indeed transcribed under all growth conditions, and at all developmental stages of growth. Further, analysis of the observed transcriptional patterns suggests the putative involvement of these components in alternative non-adhesion-specific functions, such as hyphal tip growth during germination and flagellar assembly during zoosporogenesis. Based on these results, we propose putative alternative functions for such proteins in the anaerobic gut fungi. Our results highlight the presumed diverse functionalities of FA scaffolding proteins in basal fungi. PMID- 27685798 TI - Potpourri for the holiday season. PMID- 27685795 TI - Full-Length Isoform Sequencing Reveals Novel Transcripts and Substantial Transcriptional Overlaps in a Herpesvirus. AB - Whole transcriptome studies have become essential for understanding the complexity of genetic regulation. However, the conventionally applied short-read sequencing platforms cannot be used to reliably distinguish between many transcript isoforms. The Pacific Biosciences (PacBio) RS II platform is capable of reading long nucleic acid stretches in a single sequencing run. The pseudorabies virus (PRV) is an excellent system to study herpesvirus gene expression and potential interactions between the transcriptional units. In this work, non-amplified and amplified isoform sequencing protocols were used to characterize the poly(A+) fraction of the lytic transcriptome of PRV, with the aim of a complete transcriptional annotation of the viral genes. The analyses revealed a previously unrecognized complexity of the PRV transcriptome including the discovery of novel protein-coding and non-coding genes, novel mono- and polycistronic transcription units, as well as extensive transcriptional overlaps between neighboring and distal genes. This study identified non-coding transcripts overlapping all three replication origins of the PRV, which might play a role in the control of DNA synthesis. We additionally established the relative expression levels of gene products. Our investigations revealed that the whole PRV genome is utilized for transcription, including both DNA strands in all coding and intergenic regions. The genome-wide occurrence of transcript overlaps suggests a crosstalk between genes through a network formed by interacting transcriptional machineries with a potential function in the control of gene expression. PMID- 27685799 TI - Timing of postoperative respiratory emergencies: when do they really occur? AB - PURPOSE OF REVIEW: Opioid-induced postoperative respiratory depression has garnered attention and calls for vigilance. However, a higher level of monitoring equates to increased use of hospital resources and is impractical to apply for all postoperative patients. Understanding the temporal pattern of postoperative respiratory emergency occurrences would allow for improved triage of monitoring resources for high-risk patients. Our objective is to describe the temporal pattern of risk of postoperative opioid-induced respiratory failure. RECENT FINDINGS: The literature suggests that postoperative opioid-induced respiratory depression is more frequent and severe than previously believed. In response, national patient advocacy groups have proposed improved postoperative monitoring of high-risk patients, especially those with sleep-disordered breathing. Published series of patients who have had adverse respiratory events suggest that the first 24 postsurgical hours comprise the period of highest risk, with most events occurring within the first 12 h. Further, study findings have suggested that adverse respiratory events often occur shortly after administration of opioid analgesics. SUMMARY: Emerging evidence indicates that the first postsurgical day carries the highest risk of adverse respiratory events, and this risk is often associated with opioid administration. Resources for increased monitoring should be directed to these high-risk times. PMID- 27685801 TI - Prefrontal cortex, temporal cortex, and hippocampus volume are affected in suicidal psychiatric patients. AB - Suicide is a leading cause of death in America, with over 40,000 reported suicides per year. Mental illness is a major risk factor for suicidality. This study attempts to validate findings of volumetric differences from studies on suicidality. Psychiatric inpatients classified as having mildly severe or severe depression were separated into two groups: suicide attempted in the past two months (SA; n=20), non-suicidal control group (DA; n=20); these patients were all depressed and not significantly different for age, gender, race, marital status, education level, anxiety level, and substance abuse. Healthy controls (HC; n=20) were not significantly different from the suicidal groups for age and gender. Volunteers underwent MRI to assess volumes of cortical lobes, corpus callosum, and subcortical regions of interest, including the thalamus, insula, limbic structures, and basal ganglia. The right hippocampal volume of the SA group was significantly reduced compared to healthy controls. The frontal and temporal lobe volumes of the SA group were significantly decreased compared to the DA group. These volumetric reductions confirm previous findings and support the hypothesis that fronto-temporal function may be altered in suicidal patients. PMID- 27685800 TI - Altered neurotransmitter metabolism in adolescents with high-functioning autism. AB - Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few 1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using 1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents. PMID- 27685802 TI - Less Empathic and More Reactive: The Different Impact of Childhood Maltreatment on Facial Mimicry and Vagal Regulation. AB - Facial mimicry and vagal regulation represent two crucial physiological responses to others' facial expressions of emotions. Facial mimicry, defined as the automatic, rapid and congruent electromyographic activation to others' facial expressions, is implicated in empathy, emotional reciprocity and emotions recognition. Vagal regulation, quantified by the computation of Respiratory Sinus Arrhythmia (RSA), exemplifies the autonomic adaptation to contingent social cues. Although it has been demonstrated that childhood maltreatment induces alterations in the processing of the facial expression of emotions, both at an explicit and implicit level, the effects of maltreatment on children's facial mimicry and vagal regulation in response to facial expressions of emotions remain unknown. The purpose of the present study was to fill this gap, involving 24 street children (maltreated group) and 20 age-matched controls (control group). We recorded their spontaneous facial electromyographic activations of corrugator and zygomaticus muscles and RSA responses during the visualization of the facial expressions of anger, fear, joy and sadness. Results demonstrated a different impact of childhood maltreatment on facial mimicry and vagal regulation. Maltreated children did not show the typical positive-negative modulation of corrugator mimicry. Furthermore, when only negative facial expressions were considered, maltreated children demonstrated lower corrugator mimicry than controls. With respect to vagal regulation, whereas maltreated children manifested the expected and functional inverse correlation between RSA value at rest and RSA response to angry facial expressions, controls did not. These results describe an early and divergent functional adaptation to hostile environment of the two investigated physiological mechanisms. On the one side, maltreatment leads to the suppression of the spontaneous facial mimicry normally concurring to empathic understanding of others' emotions. On the other side, maltreatment forces the precocious development of the functional synchronization between vagal regulation and threatening social cues facilitating the recruitment of fight-or-flight defensive behavioral strategies. PMID- 27685803 TI - Lake eutrophication and brownification downgrade availability and transfer of essential fatty acids for human consumption. AB - Fish are an important source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for birds, mammals and humans. In aquatic food webs, these highly unsaturated fatty acids (HUFA) are essential for many physiological processes and mainly synthetized by distinct phytoplankton taxa. Consumers at different trophic levels obtain essential fatty acids from their diet because they cannot produce these sufficiently de novo. Here, we evaluated how the increase in phosphorus concentration (eutrophication) or terrestrial organic matter inputs (brownification) change EPA and DHA content in the phytoplankton. Then, we evaluated whether these changes can be seen in the EPA and DHA content of piscivorous European perch (Perca fluviatilis), which is a widely distributed species and commonly consumed by humans. Data from 713 lakes showed statistically significant differences in the abundance of EPA- and DHA-synthesizing phytoplankton as well as in the concentrations and content of these essential fatty acids among oligo-mesotrophic, eutrophic and dystrophic lakes. The EPA and DHA content of phytoplankton biomass (mgHUFAg-1) was significantly lower in the eutrophic lakes than in the oligo-mesotrophic or dystrophic lakes. We found a strong significant correlation between the DHA content in the muscle of piscivorous perch and phytoplankton DHA content (r=0.85) as well with the contribution of DHA-synthesizing phytoplankton taxa (r=0.83). Among all DHA synthesizing phytoplankton this correlation was the strongest with the dinoflagellates (r=0.74) and chrysophytes (r=0.70). Accordingly, the EPA+DHA content of perch muscle decreased with increasing total phosphorus (r2=0.80) and dissolved organic carbon concentration (r2=0.83) in the lakes. Our results suggest that although eutrophication generally increase biomass production across different trophic levels, the high proportion of low-quality primary producers reduce EPA and DHA content in the food web up to predatory fish. Ultimately, it seems that lake eutrophication and brownification decrease the nutritional quality of fish for human consumers. PMID- 27685804 TI - Identification of beta Clamp-DNA Interaction Regions That Impair the Ability of E. coli to Tolerate Specific Classes of DNA Damage. AB - The E. coli dnaN-encoded beta sliding clamp protein plays a pivotal role in managing the actions on DNA of the 5 bacterial DNA polymerases, proteins involved in mismatch repair, as well as several additional proteins involved in DNA replication. Results of in vitro experiments indicate that the loading of beta clamp onto DNA relies on both the DnaX clamp loader complex as well as several discrete sliding clamp-DNA interactions. However, the importance of these DNA interactions to E. coli viability, as well as the ability of the beta clamp to support the actions of its numerous partner proteins, have not yet been examined. To determine the contribution of beta clamp-DNA interactions to the ability of E. coli to cope with different classes of DNA damage, we used alanine scanning to mutate 22 separate residues mapping to 3 distinct beta clamp surfaces known or nearby those known to contact the DNA template, including residues P20-L27 (referred to here as loop I), H148-Y154 (loop II) and 7 different residues lining the central pore of the beta clamp through which the DNA template threads. Twenty of these 22 dnaN mutants supported bacterial growth. While none of these 20 conferred sensitivity to hydrogen peroxide or ultra violet light, 12 were sensitized to NFZ, 5 were sensitized to MMS, 8 displayed modestly altered frequencies of DNA damage-induced mutagenesis, and 2 may be impaired for supporting hda function. Taken together, these results demonstrate that discrete beta clamp-DNA interaction regions contribute to the ability of E. coli to tolerate specific classes of DNA damage. PMID- 27685805 TI - Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era. AB - Importance: A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. Objective: To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. Design, Setting, and Participants: The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Main Outcome Measures: Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). Results: From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P < .001), from 896.4 to 414.9 for CIN2 (APC, -10.5; 95% CI, -18.8 to -1.2; P = .03), and from 240.2 to 0 for CIN3 (APC, -41.3; 95% CI, -65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, 6.3; 95% CI, -10.9 to -1.4; P = .02). Conclusions and Relevance: Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination. PMID- 27685806 TI - Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions. AB - BACKGROUND: Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. OBJECTIVES: We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. METHODS: We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. RESULTS: Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175MUg/mL, n = 51) and in healthy women (90-176MUg/mL, n = 74), while HK cleavage was lower (p<0.001) in men (0-5%) than women (3-9%). Patients exhibited lower native HK concentration (p<10-4; 21-117MUg/mL, n = 31 for men; 0-84MUg/mL, n = 41 for women) and higher HK cleavage (p<10-4; 10-30% and 14-89%, respectively) than healthy donors. Pathological thresholds were set at: <72MUg/mL native HK, >14.4% HK cleavage for men; <38MUg/mL; native HK, >33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13) or two weeks after AE attack (n = 2), HK cleavage was not fully restored, suggesting its use as a post-attack assay. CONCLUSION: As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management. PMID- 27685807 TI - The Role of Cystathionine-gamma-Lyase In Blunt Chest Trauma in Cigarette Smoke Exposed Mice. AB - Pretraumatic cigarette smoke (CS) exposure aggravates posttraumatic acute lung injury (ALI). Cystathionine-gamma-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate posttraumatic ALI after CS exposure. After 3 to 4 weeks of CS exposure, anesthetized wild-type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4 h of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism, and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated posttraumatic alveolar membrane thickening, dystelectasis, and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pretraumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposed CSE animals. In conclusion, in murine acute on-chronic pulmonary disease, CSE knockout aggravated posttraumatic inflammation, which was further worsened upon pretraumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner. PMID- 27685808 TI - Novel Synthetic Oxazines Target NF-kappaB in Colon Cancer In Vitro and Inflammatory Bowel Disease In Vivo. AB - Aberrant activation of nuclear factor kappa B (NF-kappaB) has been linked with the pathogenesis of several proinflammatory diseases including number of cancers and inflammatory bowel diseases. In the present work, we evaluated the anticancer activity of 1,2-oxazines derivatives against colorectal cancer cell lines and identified 2-((2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3 yl)methyl)isoindoline-1,3-dione (API) as the lead anticancer agent among the tested compounds. The apoptosis inducing effect of API was demonstrated using flow cytometry analysis and measuring the caspase 3/7 activity in API treated cells. Based on the literature on inhibition of NF-kappaB by oxazines, we evaluated the effect of 1,2-oxazines against the ability of NF-kappaB binding to DNA, NF-kappaB-dependent luciferase expression and IkappaBalpha phosphorylation. We found that, API abrogate constitutive activation of NF-kappaB and inhibits IkappaBalpha phosphorylation in HCT116 cells. Our in silico analysis revealed the binding of oxazines to the hydrophobic cavity that present between the interface of p65 and IkappaBalpha. Given the relevance with aberrant activation of NF kappaB in inflammation bowel disease (IBD), we evaluated the effect of API on dextran sulphate sodium-induced IBD mice model. The treatment of IBD induced mice with API decreased the myeloperoxidase activity in colonic extract, modulated the colon length and serum levels of pro- and anti-inflammatory cytokines such as TNF alpha, IFN-gamma, IL-6, IL-1beta and IL-10. Furthermore, the histological analysis revealed the restoration of the distorted cryptic epithelial structure of colon in the API treated animals. In conclusion, we comprehensively validated the NF-kappaB inhibitory efficacy of API that targets NF-kappaB in in vitro colon cancer and an in vivo inflammatory bowel disease model. PMID- 27685810 TI - Surface Disinfectants for Burn Units Evaluated by a New Double Method, Using Microorganisms Recently Isolated From Patients, on a Surface Germ-Carrier Model. AB - Assessment methods of surface disinfection based on international standards (Environmental Protection Agency, European Norms, etc) do not correspond to hospital reality. New evaluation methods of surfaces disinfection are proposed to choose the most suitable disinfectant to act against clinically relevant microorganisms detected on the surfaces of burn units. 1) "Immediate effect": 6 products were compared using a glass germ-carrier and 20 recently isolated microorganisms from different patients in the intensive care units. Disinfectants were applied with microfiber cloths. Log10 reductions were calculated for colony forming units produced after 15 minutes of disinfectant application. 2) "Residual effect": the glass germ-carriers were previously impregnated with one of the studied disinfectants. After a 30-minute wait period, they were then contaminated with 1 microorganism (from the 20 above-mentioned). After 15 minutes, the disinfectant was inhibited and the log10 reduction of colony forming units was assessed. The immediate effect (disinfection and microorganism dragging and transferring from the surface to the cloth) produced complete elimination of the inoculums for all products used except one (a diluted quaternary ammonium). The average residual effect found on the 20 microorganisms was moderate: 2 to 3 log10 colony forming unit reduction with chlorine dioxide or 0.5% chlorhexidine (and lower with the other products), obtaining surfaces refractory to recontamination, at least, during 30 minutes. Two tests should be performed before advising surface disinfectant: 1) direct effect and 2) residual efficacy. These characteristics should be considered when a new surface disinfectant is chosen. Chlorine dioxide has a similar or better direct effect than sodium hypochlorite and a similar residual effect than chlorhexidine. PMID- 27685809 TI - Epidemiology and Outcome of Patients With Burns Treated With Cerium Nitrate Silversulfadiazine. AB - In this study, the outcome of treatment with Flammacerium in burn patients is studied. The retrospective study involved patients with acute burns admitted to the Burn Centre of Martini Hospital, Groningen, The Netherlands, between 2009 and 2014. The outcome parameters were mortality, complications (noninfectious and infectious), need of surgery, and length of stay. The group of patients consisted of 853 patients, of which 554 were male (64.9%). There were 23 patients with a total burn size of 40% TBSA or more (2.7%). In total, 13 of the 853 patients (1.5%) died, and none of them were children (<16 years). The overall mortality in the group of patient with burns >40% TBSA was 30.4%. In the elderly group (>70 years), the mortality rate was 6.3%. Treatment with Flammacerium is applicable in all thermal burn patients. Especially children, elderly patients, and patients with severe burns can benefit from a more conservative treatment with Flammacerium whereby the first operation can be postponed until the patient is stabilized and in which the wounds can be covered directly with skin transplants. PMID- 27685812 TI - First Locally Transmitted Zika Virus Cases Identified in the United States. PMID- 27685811 TI - Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes. AB - Cultured cardiomyocytes can be used to study cardiomyocyte biology using techniques that are complementary to in vivo systems. For example, the purity and accessibility of in vitro culture enables fine control over biochemical analyses, live imaging, and electrophysiology. Long-term culture of cardiomyocytes offers access to additional experimental approaches that cannot be completed in short term cultures. For example, the in vitro investigation of dedifferentiation, cell cycle re-entry, and cell division has thus far largely been restricted to rat cardiomyocytes, which appear to be more robust in long-term culture. However, the availability of a rich toolset of transgenic mouse lines and well-developed disease models make mouse systems attractive for cardiac research. Although several reports exist of adult mouse cardiomyocyte isolation, few studies demonstrate their long-term culture. Presented here, is a step-by-step method for the isolation and long-term culture of adult mouse cardiomyocytes. First, retrograde Langendorff perfusion is used to efficiently digest the heart with proteases, followed by gravity sedimentation purification. After a period of dedifferentiation following isolation, the cells gradually attach to the culture and can be cultured for weeks. Adenovirus cell lysate is used to efficiently transduce the isolated cardiomyocytes. These methods provide a simple, yet powerful model system to study cardiac biology. PMID- 27685814 TI - Safety Standards for Invasive Procedures. PMID- 27685813 TI - Super-resolution optical microscopy study of telomere structure. AB - Chromosome ends are shielded from exonucleolytic attack and inappropriate end joining by terminal structures called telomeres; these structures are potential targets for anticancer drugs. Telomeres are composed of a simple DNA sequence (5? TTAGGG-3? in humans) repeated more than a thousand times, a short 3? single stranded overhang, and numerous proteins. Electron microscopy has shown that the 3? overhang pairs with the complementary strand at an internal site creating a small displacement loop and a large double-stranded "t-loop." Our goal is to determine whether all telomeres adopt the t-loop configuration, or whether there are two or more distinct configurations. Progress in optimizing super-resolution (SR) microscopy for this ongoing investigation is reported here. Results suggest that under certain conditions sample preparation procedures may disrupt chromatin by causing loss of nucleosomes. This finding may limit the use of SR microscopy in telomere studies. PMID- 27685815 TI - The Use of Aspirin in Primary Prevention of Cardiovascular Disease. PMID- 27685816 TI - Timing of Therapeutic Hypothermia for Inborn and Outborn Infants with Neonatal Encephalopathy. AB - Therapeutic hypothermia is now the standard of care for infants with moderate to severe hypoxic ischaemic encephalopathy. Sixty-three infants received therapeutic hypothermia at Cork University Maternity Hospital (CUMH) from 2010-2014. Median gestational age was 40 weeks. Eighteen (29%) infants were Sarnat grade 3, 41(65%) grade 2 and 4(6%) grade 1. Nineteen outborn infants arrived in CUMH at a median (IQR) age of 310 (270, 420) minutes. Four (21%) outborn infants were within the target temperature range on arrival. Median (IQR) time (minutes) from birth to achieve target temperature was 136 (90, 195) for inborn and 300 (240, 360) for outborn infants (p < .01). Overall, 35 (56%) infants had electrical seizures, 42 (74%) had a normal MRI at a median (IQR) age of 7(6,9) days and the median(IQR) length of stay was 9 (7,11) days. Although no difference in seizures or MRI findings was seen, passive cooling does not achieve consistent temperature control for outborn infants. PMID- 27685817 TI - Epidemiology of Injury in Gaelic Handball. AB - The initial step in developing injury prevention strategies is to establish the epidemiology of injury. However there has been no published research on injury in Gaelic handball. This study describes the epidemiology of injury in 75 Gaelic handball players utilising a retrospective questionnaire. 88% of participants reported one or more injuries. Injuries to the upper limb were prevalent (52.9%), followed by the lower limb (30.3%). The shoulder (17.6%), finger (10.5%) and ankle (9.8%) were the primary sites of injury. Injuries occurred most frequently in December (9.7%), January (9.7%), February (9.7%) and November (8.7%). Injuries predominantly occurred during games (82.4%). Injuries were primarily severe (54.7%), with 14.6% of participants admitted to hospital due to injury. Given that this is the only study on Gaelic handball to date, prospective epidemiological studies and further research on injury prevention strategies are necessary. PMID- 27685818 TI - The Association Between 25 Hydroxyvitamin D and Airway Obstruction in Asthma. AB - Since Vitamin D has anti-inflammatory effects we wondered whether the association between low serum 25OHD and airway obstruction in moderate persistent asthma might be explained by inflammatory pathways that worsen asthma. All subjects examined were Irish Caucasians with moderate persistent asthma and none took systemic steroid therapy. In addition to computerized spirometry, we measured BMI, serum 25-hydroxyvitamin D (25OHD), total IgE, Eosinophil Cationic Protein (ECP), and high sensitive C- reactive protein (hs-CRP). One hundred (47 male) subjects completed the testing. Within single level of asthma severity, 25OHD levels were related to post-bronchodilator FEV1/FVC (r = 0.26, p< 0.01), but multiple linear regression analysis demonstrated that the association was not explained by obesity or inflammatory markers. We find a relationship exists between airway obstruction and 25OHD levels in asthmatic adults, and the effect is not explained by the presence of potential confounders such as obesity, allergy and systemic inflammation. PMID- 27685819 TI - Spontaneous Pneumothorax; a Collapse in Management? AB - Revised guidelines for the management of spontaneous pneumothoraces were published by the British Thoracic Society in 2010, however compliance remains poor. A retrospective review was performed on patients diagnosed with a pneumothorax over a 26 month period (January 2012 to March 2014). Of the 57 patients identified, 43 (75%) were diagnosed with spontaneous pneumothorax. 12 patients (21%) had pre-existing lung disease, and 16 patients (28%) admitted to having had a previously documented pneumothorax. 19 patients (33%) were reported as smokers. The main symptoms reported were chest pain (93%) and shortness of breath (54%). Observation was appropriate in 18 cases (31%), while aspiration alone was performed in 9 (16%) with chest drains required in 25 cases (44%). Five patients (9%) were admitted directly under a medical team. Our study demonstrated good compliance with BTS guidelines. The decision to observe, aspirate, insert a chest drain or directly refer to the medical team was appropriate in the majority of cases studied. PMID- 27685820 TI - Headache Management in Community Pharmacies. AB - Many headache patients self-medicate and choose their preferred analgesic from a range of acute analgesics available on the high-street and from community pharmacies. Little is known about their presenting symptoms, headache diagnosis and their preferred treatments. A questionnaire was distributed to community pharmacies in the Munster region of Ireland and was administered to patients requesting treatment for headache. A total of 1023 completed questionnaires were received, 76.7% (n=765) were female and 51.8% were aged 18-39 years. 53.3% (n=542) were not previously diagnosed by a GP and 49.6% (n=502) had never sought advice from a pharmacist. According to the symptoms described, 32% (n=327) had episodic migraine and a further 15.2% (n=155) had probable episodic migraine. 30.3% (n=310) had tension type headache. 10.7% (n=105) had chronic daily headache. Codeine based products were the preferred treatment choice for 43.1% (n=441). Triptans were the most effective, 68.6% (n=166), in those for whom they were previously prescribed. 11.8% (n=121) had medication-overuse. The community pharmacist is an important resource in headache management. An expanded role incorporating best practice management guidelines has the potential to improve the outcomes for many headache sufferers. PMID- 27685821 TI - Group B Streptoccocal Meningitis and Ventriculo-peritoneal Shunts. AB - There is no available Irish data on the rate of Ventriculo-peritoneal (VP) shunt insertion in infants with group B streptococcus (GBS) meningitis. We performed a retrospective case series of 40 infants with GBS meningitis over 6 years. Four (10%) infants required insertion of VP shunt for hydrocephalus. Those infants who required a VP shunt initially presented with seizures, lethargy and a low serum white cell count. PMID- 27685822 TI - Osteosarcoma in a Patient Receiving Long-Term TNF Inhibitor Therapy. AB - Patients with inflammatory bowel disease (IBD) have an increased risk of developing malignancy. The use of immunosuppressive therapies and tumour necrosis factor (TNF) inhibitors in these patients may provide a further risk for the development of malignancy. We report the clinical and pathological findings of a high grade osteosarcoma in a patient with Crohns disease receiving TNF inhibitor therapy. In this case, a 32-year old female presented with a painful right knee after receiving maintenance adalimumab for Crohns disease for a period of six years. There is a substantial hypothetical link between TNF inhibitor regimens such as adalimumab and an increased risk of malignancy. TNF inhibitor therapy should be ceased and chemotherapy and surgery is an effective combined modality approach in these patients. The role of TNF inhibitors in patients after cancer diagnosis is uncertain and further research is required to assess efficacy and safety. PMID- 27685823 TI - Superficial Siderosis. AB - Herein, we describe a case of 69 year old man who presented with gradual bilateral hearing impairment and unsteadiness. Examination showed bilateral sensorineural deafness and cerebellar ataxia. Neuroimaging revealed a rim of hypointensity surrounding the brain stem, superficial cerebellar fissures and extending into the cervical spinal cord consistent with the diagnosis of superficial siderosis (SS). Investigations failed to identify any reversible cause for the condition. PMID- 27685824 TI - Patients safety incident reporting: the who, what, where, when and why? AB - The landscape of patient safety is changing nationally and internationally. Recently, the number of preventable deaths in the USA annually is estimated at between 200,000-400,000.Nationally and internationally under-reporting of patient safety incidents is an opportunity for improvement. In 2015, 58.6% of patient related claims received by the State Claims Agency (SCA) had no previous patient safety incident reported, despite the legal obligation to report adverse events to the SCA. A detailed, national survey of the acute hospitals identified that there is significant variation in the modes and patterns of incident reporting, including variation in the percentage of incidents reported to the SCA, who decides what is reported, how it is reported, the backlog of incidents not reported and the time delay before reporting. This knowledge confirms that currently, comparisons between hospitals of equal activity are inaccurate. Reduction in variation and increased standardisation of patient safety incident reporting is required. PMID- 27685825 TI - A Case of Sporadic Pulmonary Lymphangioleiomyomatosis. PMID- 27685826 TI - Which Factors are Important in Determining the Length of Stay in Bronchiolitis? PMID- 27685827 TI - Appropriateness of Medical Admissions and of Continued In-Patient Stay at an Acute Hospital. PMID- 27685828 TI - Encouraging Oral Analgesia in the Fasted Child Attending a Trauma Review Clinic. PMID- 27685829 TI - Oxygen-Molecule Adsorption and Dissociation on BCN Graphene: A First-Principles Study. AB - Boron and nitrogen co-doped (BCN) graphene is an attractive material for use as a metal-free oxygen reduction reaction electrocatalyst and as other catalysts due to its unique structure and electronic properties. Reported here is the structure, determined by using density functional theory, of the active O2 dissociation site of BCN graphene containing different types of BN cluster. The results show that the edge termination and shape of substitutional BN clusters are two important factors that determine the catalytic activity of BCN graphene for the dissociation of molecular oxygen. N-Terminated triangular BN (t-BN) cluster doping can reduce the energy barrier more effectively compared to a t-BN with a B edge or quadrangular BN cluster. Interestingly, the B atom neighboring the N edge, only in the case of N-terminated t-BN doping, is determined to be the most active site for O2 dissociation due to the barrier being as low as 0.08 eV. The electronic structure calculations reveal that in addition to the large positive charge densities, the catalytic activity of graphene enhanced by B,N doping is also attributed to the increased density of states of the pi* states of the active site around the Fermi level. PMID- 27685830 TI - Doctors and Witches, Conscience and Violence: Abortion Provision on American Television. AB - CONTEXT: Popular entertainment may reflect and produce-as well as potentially contest-stigma regarding abortion provision. Knowledge of how providers are portrayed on-screen is needed to improve understanding of how depictions may contribute to the stigmatization of real providers. METHODS: All abortion provision plotlines on American television from 2005 to 2014 were identified through Internet searches. Plotlines were assessed in their entirety and coded for genre, abortion provision space, provider characteristics, method and efficacy of provision, and occurrence of violence. Inductive content analysis was used to identify themes in how these features were depicted. RESULTS: Fifty-two plotlines involving abortion provision were identified on 40 television shows; a large majority of plotlines appeared in dramas, particularly in the subgenre of medical dramas. Medical spaces were depicted as normal and safe for abortion provision, and nonmedical spaces were often portrayed as remote and unsafe. Legal abortion care using medical methods was depicted as effective and safe, and legal providers were presented as compassionate, while providers operating outside of medical and legal authority were depicted as ineffective, dangerous and uncaring. Fictional providers were largely motivated by the belief that abortion provision is a necessary and moral service. Plotlines linked abortion provision to violence. CONCLUSIONS: The differing ways in which legal and illegal abortion are portrayed reveal potential consequences regarding real-world abortion provision, and suggest that representations situated in medical contexts may work to legitimate and destigmatize such provision. PMID- 27685831 TI - Water-dispersible Hollow Microporous Organic Network Spheres as Substrate for Electroless Deposition of Ultrafine Pd Nanoparticles with High Catalytic Activity and Recyclability. AB - Microporous organic networks (MONs) have been considered as an ideal substrate to stabilize active metal nanoparticles. However, the development of highly water dispersible hollow MONs nanostructures which can serve as both the reducing agent and stabilizer is highly desirable but still challenging. Here we report a template-assisted method to synthesize hollow microporous organic network (H-MON) spheres using silica spheres as hard template and 1,3,5-triethynylbenzene as the building blocks through a Glaser coupling reaction. The obtained water dispersible H-MON spheres bearing sp- and sp2 -hybridized carbon atoms possess a highly conjugated electronic structure and show low reduction potential; thus, they can serve as a reducing agent and stabilizer for electroless deposition of highly dispersed Pd clusters to form a Pd/H-MON spherical hollow nanocomposite. Benefitting from their high porosity, large surface area, and excellent solution dispersibility, the as-prepared Pd/H-MON hollow nanocomposite exhibits a high catalytic performance and recyclability toward the reduction of 4-nitrophenol. PMID- 27685832 TI - Emergency nurses' decisions regarding frequency and nature of vital sign assessment. AB - AIMS AND OBJECTIVES: To explore the factors emergency nurses use to inform their decisions regarding frequency and nature of vital sign assessment. BACKGROUND: Research related to clinical deterioration and vital sign assessment in the emergency department is in its infancy. Studies to date have explored the frequency of vital sign assessment in the emergency department; however, there are no published studies that have examined factors that emergency nurses use to inform their decisions regarding frequency and nature of ongoing vital sign assessment. DESIGN: A prospective exploratory design was used. Data were collected using a survey consisting of eight patient vignettes. METHODS: The study was conducted in one emergency department in metropolitan Melbourne. Participants were emergency nurses permanently employed at the study site. RESULTS: A 96% response rate was achieved (n = 47/49). The most common frequency of patient reassessment nominated by participants was 15 or 30 minutely, with an equal number of participants choosing these frequency intervals. Abnormality in initial vital sign parameters was the most common factor identified for choosing either a 15- or 30-minute assessment interval. Frequency of assessment decisions was influenced by years of emergency nursing experience in one vignette and level of postgraduate qualification in three vignettes. Heart rate, respiratory rate and blood pressure were all nominated by over 80% of participants as vital signs that participants considered important for reassessment. The frequency and nature of vital signs selected varied according to vignette content. There were significant negative correlations between assessment of conscious state and years of nursing experience and assessment of respiratory rate and years of emergency nursing experience. Level of postgraduate qualification did not influence selection of parameters for reassessment. CONCLUSION: Emergency nurses are tailoring vital sign assessment to patients' clinical status, and nurses are integrating known vital sign data into vital sign decision-making. RELEVANCE TO CLINICAL PRACTICE: Accurate assessment and interpretation of vital sign data is fundamental to patient safety. Emergency nurses are responsible for the initial and ongoing assessment of undiagnosed or undifferentiated patients. Prior to medical assessment, emergency nurses are solely responsible for patient assessment, escalation of care and implementation of interventions within nursing scope of practice. PMID- 27685834 TI - Behavioral History of Withdrawal Influences Regulation of Cocaine Seeking by Glutamate Re-Uptake. AB - Withdrawal from cocaine regulates expression of distinct glutamate re-uptake transporters in the nucleus accumbens (NAc). In this study, we examined the cumulative effect of glutamate re-uptake by multiple excitatory amino acid transporters (EAATs) on drug-seeking at two different stages of withdrawal from self-administered cocaine. Rats were trained on fixed ratio 1 (FR1), progressing to FR5 schedule of reinforcement. After one day of withdrawal, microinfusion of a broad non-transportable EAAT antagonist, DL-threo-beta-benzyloxyaspartate (DL TBOA), into the NAc shell dose-dependently attenuated self-administration of cocaine. Sucrose self-administration was not affected by DL-TBOA, indicating an effect specific to reinforcing properties of cocaine. The attenuating effect on cocaine seeking was not due to suppression of locomotor response, as DL-TBOA was found to transiently increase spontaneous locomotor activity. Previous studies have established a role for EAAT2-mediated re-uptake on reinstatement of cocaine seeking following extended withdrawal and extinction training. We found that blockade of NAc shell EAATs did not affect cocaine-primed reinstatement of cocaine seeking. These results indicate that behavioral history of withdrawal influences the effect of re-uptake mediated glutamate clearance on cocaine seeking. Dynamic regulation of glutamate availability by re-uptake mechanisms may impact other glutamate signaling pathways to account for such differences. PMID- 27685833 TI - Nutraceuticals in hypercholesterolaemia: an overview. AB - : Growing attention is now being given to the possible preventive/alternative ways to avoid illness onset. Changes in lifestyle and food habits are taking over from the conventional pharmaceutical-based approach, especially for chronic pathologies. Nutraceuticals have been proposed as key tools for the prevention and cure of some pathological conditions. This is leading research to develop new formulations based on these pharma-foods addressed in a specific way to prevent and cure health issues, which, in turn, will have an effect on therapy-related costs sustained by any National Health Organization. According to existing regulations, nutraceuticals cannot be categorized as either food or drugs but, by definition, often inhabit a grey area in between the two, being assimilated into food supplements, notwithstanding the beneficial properties that they can provide for some pathological conditions. A nutraceuticals-based approach for health management, in particular for some pathological conditions, has resulted in a worldwide growing 'nutraceutical' revolution. An outstanding example is the approach to the 'metabolic syndrome', which includes overweight, obesity and cardiovascular-related diseases, causing a sort of cascade of chronic health conditions, which is becoming a norm in modern life. Hypercholesterolaemia is one of these. It represents an example of a pathology that can be linked to both a poor lifestyle and dietary habits. The nutraceutical approach to hypercholesterolaemia is described in the present review as a possible alternative to the conventional drug-based therapy. LINKED ARTICLES: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. PMID- 27685836 TI - Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study. AB - Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i.e., "focused cancer immunotherapy") based on tumor antigens that are specifically expressed in the tumor of a certain cancer and in many patients with this cancer. Immune complexes (ICs) are the direct and stable products of immunological recognition by humoral immunity. Here, we searched for tumor-specific IC antigens in each of five cancers (lung (n = 28), colon (n = 20), bladder (n = 20), renal cell (n = 15) and malignant lymphoma (n = 9)), by using immune complexome analysis that comprehensively identifies and profiles the constituent antigens in ICs. This analysis indicated that gelsolin and inter alpha-trypsin inhibitor heavy chains were specifically and frequently detected (at a frequency higher than 80%), and that phosphoproteins (VENTX, VCIP135) were also specifically present in the ICs of lung cancer patients. Immune complexome analysis successfully identified several tumor-specific IC antigens with high detection frequency in lung cancer patients. These specific antigens are required to validate the clinical benefit by further analysis using a large number of patients. PMID- 27685835 TI - The extreme hyper-reactivity of selected cysteines drives hierarchical disulfide bond formation in serum albumin. AB - After mild reduction of serum albumin, seven among the 34 cysteines forming the disulfide network displayed a surprising hyper-reactivity. Compared to the thiol group of glutathione, the average reactivity of these cysteines towards disulfides and thiol reagents was more than 100 times higher. Using mass spectrometry and kinetic data, we identified all these unusual residues, with Cys75, Cys123 and Cys264 showing the highest reactivity. This effect was mainly due to a low pKa of the sulfhydryl groups and may explain the very fast formation of early disulfides in the nascent protein suggesting the existence of a hierarchical propensity to form such covalent links in selected regions during oxidative folding. An identical pattern of hyper-reactive cysteines was found in albumins from six different mammals. This hyper-reactivity is much higher than the one found in other proteins containing multiple cysteines only devoted to structural disulfide bonds. It is possible that such hyper-reactive cysteines could also be present in other proteins, although their existence has been completely ignored so far. PMID- 27685837 TI - CD163 levels, pro- and anti-inflammatory cytokine secretion of monocytes in children with pulmonary tuberculosis. AB - OBJECTIVES: Childhood tuberculosis (TB) comprises an important part of the world's TB burden. Monocytes set up the early phase of infection because of innate immune responses. Understanding the changes in monocyte subsets during multisystem infectious diseases may be important for the development of novel diagnostic and therapeutic strategies. The aim of this study was to evaluate the monocyte phenotype together with the cytokine secretion profiles of children with pulmonary tuberculosis. STUDY DESIGN: Thirteen patients with pulmonary TB were enrolled as study group, and 14 healthy subjects as control group. Surface expressions of CD16, CD14, CD62L, CD163, CCR2, and HLA-DR of monocytes were analyzed by flow cytometry. The presence of IFN-gamma, TNF-alpha, IL-10, IL-12, IL-23, and soluble form of CD163 (sCD163) in the antigen- and LPS-stimulated whole blood culture supernatants were detected using ELISA and Luminex. RESULTS: Higher percentages of CD14++ CD16+ and CD14+ CD16++ monocyte subsets, and CCR2, CD62L and CD163 expression on circulating monocytes in children with pulmonary tuberculosis were obtained. Diminished levels of ESAT-6/CFP-10-induced IL-10 and increased levels of TB-antigen and LPS-stimulated sCD163 were found in childhood with pulmonary TB. CONCLUSIONS: High expression of CD14++ CD16+ , CD14+ CD16++ , CD14+ CCR2+ , and CD14+ CD62L+ cells in childhood TB, and monocyte-derived cytokines reflected both pro- and anti-inflammatory profiles. Higher sCD163 and CD14+ CD163+ monocytes might help physicians in the differential diagnosis of pulmonary TB in children. Pediatr Pulmonol. 2017;52:675-683. (c) 2016 Wiley Periodicals, Inc. PMID- 27685839 TI - Uncatalyzed Hydrogenation of First-Row Main Group Multiple Bonds. AB - Room temperature hydrogenation of an SIDep-stabilized diboryne (SIDep=1,3 bis(diethylphenyl)-4,5-dihydroimidazol-2-ylidene) and a cAAC-supported diboracumulene (cAAC=1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2 ylidene) provided the first selective route to the corresponding 1,2 dihydrodiborenes. DFT calculations showed an overall exothermic (DeltaG=19.4 kcal mol-1 ) two-step asynchronous H2 addition mechanism proceeding via a bridging hydride. PMID- 27685838 TI - National survey of colistin resistance among carbapenemase-producing Enterobacteriaceae and outbreak caused by colistin-resistant OXA-48-producing Klebsiella pneumoniae, France, 2014. AB - From January 2014 to December 2014, 972 consecutive non-replicate carbapenemase producing Enterobacteriaceae isolates from colonised or infected patients were collected at the Associated French National Reference Centre as part of the French national survey on antimicrobial resistance. It included 577 Klebsiella spp. (59%), 236 Escherichia coli (24%), 108 Enterobacter spp. (11%), 50 Citrobacter spp. (5%), and a single Salmonella spp. isolate (0.1%). Of 561 K. pneumoniae isolates, 35 were found to be resistant to colistin (6.2%). PFGE analysis revealed a clonal outbreak involving 15 K. pneumoniae isolates belonging to sequence type ST11, recovered in a single hospital in the Picardie region in northern France. Those clonally related isolates showed variable levels of resistance to colistin, ranging from 4 to 64 mg/L. They harboured the blaOXA-48 carbapenemase gene and the blaCTX-M-15 extended-spectrum beta-lactamase gene. Among the 91 Enterobacter cloacae isolates, seven were resistant to colistin and produced different types of carbapenemases. Surprisingly, none of the E. coli and Citrobacter spp. isolates showed resistance to colistin. This national survey including carbapenemase-producing isolates recovered in 2014 reported a high rate of colistin resistance in K. pneumoniae and E. cloacae (6.2% and 7.7%, respectively) in France. PMID- 27685840 TI - In Vitro Evaluation of the Size, Knot Holding Capacity, and Knot Security of the Forwarder Knot Compared to Square and Surgeon's Knots Using Large Gauge Suture. AB - OBJECTIVE: To investigate the strength, size, and holding capacity of the self locking forwarder knot compared to surgeon's and square knots using large gauge suture. STUDY DESIGN: In vitro mechanical study. STUDY POPULATION: Knotted suture. METHODS: Forwarder, surgeon's, and square knots were tested on a universal testing machine under linear tension using 2 and 3 USP polyglactin 910 and 2 USP polydioxanone. Knot holding capacity (KHC) and mode of failure were recorded and relative knot security (RKS) was calculated as a percentage of KHC. Knot volume and weight were assessed by digital micrometer and balance, respectively. ANOVA and post hoc testing were used tocompare strength between number of throws, suture, suture size, and knot type. P<.05 was considered significant. RESULTS: Forwarder knots had a higher KHC and RKS than surgeon's or square knots for all suture types and number of throws. No forwarder knots unraveled, but a proportion of square and surgeon's knots with <6 throws did unravel. Forwarder knots had a smaller volume and weight than surgeon's and square knots with equal number of throws. The forwarder knot of 4 throws using 3 USP polyglactin 910 had the highest KHC, RKS, and the smallest size and weight. CONCLUSION: Forwarder knots may be an alternative for commencing continuous patterns in large gauge suture, without sacrificing knot integrity, but further in vivo and ex vivo testing is required to assess the effects of this sliding knot on tissue perfusion before clinical application. PMID- 27685841 TI - Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI. AB - ARHI is an imprinted tumor suppressor gene and its methylation suppresses ARHI transcription levels to cause the development and progression of malignant tumors. Zebularine exerts a demethylation function for tumor suppressor genes. Our study aims to investigate the effect and mechanism of action of zebularine on the epigenetic modification of the ARHI gene, and whether this effect may modulate the viability and apoptosis of human osteosarcoma cells. We found that zebularine inhibited the viability and promoted apoptosis in osteosarcoma cells. Zebularine potentiated the expression of ARHI at both the protein and mRNA level. This was related to the downregulation of methylation of ARHI caused by zebularine. Zebularine suppressed the interaction of DNA methyltransferase 1 (DNMT1) with histone methyltransferase G9a, but had no effect on G9a alone. Knockdown of DNMT1 or G9a can induce a reduction of ARHI methylation. Therefore, we inferred that zebularine was likely to directly repress DNMT1 alone, but G9a was necessary to regulate the function of DNMT1 on ARHI methylation. Moreover, knockdown of ARHI rescued cell viability and apoptosis under the zebularine treated condition. We showed that zebularine inhibited viability and promoted apoptosis by disturbing the interaction between DNMT1 and G9a, thereby resulting in lower ARHI methylation and elevated ARHI expression in osteosarcoma cells. PMID- 27685843 TI - Site-specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis. AB - The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer. We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples. CpG island hypermethylation status of the three genes was analyzed using quantitative methylation-specific PCR (Q-MSP). In order to determine the prognostic value of the methylation status of these genes, the associations between methylation index and various clinical characteristics, especially tumor site, were assessed for tumors from patients with HNSCC. The methylation index was positively correlated with female gender (P = 0.008) and disease recurrence (P = 0.01) in oral cancer and human papillomavirus (HPV) positive (P = 0.004) status and disease recurrence (P = 0.005) in oropharyngeal cancer. Among patients with oral and oropharyngeal cancer, promoter hypermethylation of GAL, GALR1, or GALR2 was statistically correlated with a decrease in disease-free survival (log-rank test, P = 0.036 and P = 0.042, respectively). Furthermore, methylation of GAL, GALR1, or GALR2 exhibited the highest association with poor survival (log-rank test, P = 0.018) in patients with HPV-negative oropharyngeal cancers. As such, GAL and GALR1/2 methylation status may serve as an important site-specific biomarker for prediction of clinical outcome in patients with HNSCC. (c) 2016 Wiley Periodicals, Inc. PMID- 27685842 TI - Is the Noradrenergic Symptom Cluster a Valid Construct in Adjunctive Treatment of Major Depressive Disorder? AB - OBJECTIVE: To identify symptoms potentially representative of a noradrenergic symptom cluster as possible predictors of response to the selective norepinephrine reuptake inhibitor (NRI) edivoxetine when used as monotherapy or adjunctive treatment in patients with DSM-IV-TR major depressive disorder (MDD). METHODS: Pooled data from 4 adjunctive treatment trials (selective serotonin reuptake inhibitor [SSRI] + edivoxetine 6-18 mg/d vs SSRI + placebo; N = 2,066) and data from 1 monotherapy trial (edivoxetine 6-18 mg/d versus placebo; N = 495) were used to identify predictors of response related to noradrenergic symptoms using a resampling-based ensemble tree method. The trials were conducted from 2008 to 2013. RESULTS: In the pooled adjunctive trials, no subgroup was identified that demonstrated a greater edivoxetine-placebo treatment difference than the overall patient cohort. In the edivoxetine monotherapy trial, no subgroup showing greater mean edivoxetine-placebo differences on the Montgomery Asberg Depression Rating Scale versus the overall patient cohort was identified; a subgroup (67%) with high baseline Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) total score (>= 28) showed statistically significantly (P = .02) greater mean edivoxetine-placebo differences on the Sheehan Disability Scale versus the overall patient cohort, and subgroups with baseline CPFQ total score >= 28 (65%), CPFQ cognition dimension score >= 16 (63%), or CPFQ physical dimension score >= 13 (59%) showed statistically significantly (P <= .025) greater mean edivoxetine-placebo differences on the CPFQ total score versus the overall patient cohort. CONCLUSIONS: While we could not identify symptoms predictive of response to the selective NRI edivoxetine used as adjunctive treatment, impaired cognition and physical symptoms may predict greater improvement during monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00840034, NCT01173601, NCT01187407, NCT01185340, NCT00795821. PMID- 27685844 TI - Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma. AB - BACKGROUND: MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. METHODS: Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers. The discriminatory ability of the evaluated plasma miRNAs between patients and controls was evaluated with receiving operating characteristic (ROC) curves. RESULTS: Small RNAs from 12 ICC and 11 tumor-free liver samples were evaluated. Unsupervised hierarchical clustering using the miRNA expression data showed clear grouping of ICC vs. non-neoplastic liver parenchyma. We identified 134 down regulated and 128 upregulated miRNAs. Based on overexpression and high fold change, miR21, miR200b, miR221, and miR34c were measured in plasma from an independent cohort of patients with ICC (n = 25) and healthy controls (n = 7). Significant overexpression of miR-21 and miR-221 was found in plasma from ICC patients. Furthermore, circulating miR-21 demonstrated a high discriminatory ability between patients with ICC and healthy controls (AUC: 0.94). CONCLUSION: Among the differentially expressed miRNAs in ICC, miR-21 and miR-221 are overexpressed and detectable in the circulation. Plasma expression levels of these miRNAs, particularly miR-21, accurately differentiates patients with ICC from healthy controls and could potentially serve as adjuncts in diagnosis. Prospective validation and comparison with other hepatobiliary malignancies is required to establish their potential role as diagnostic and prognostic biomarkers. PMID- 27685846 TI - Unusual Salt and pH Induced Changes in Polyethylenimine Solutions. AB - Linear PEI is a cationic polymer commonly used for complexing DNA into nanoparticles for cell-transfection and gene-therapy applications. The polymer has closely-spaced amines with weak-base protonation capacity, and a hydrophobic backbone that is kept unaggregated by intra-chain repulsion. As a result, in solution PEI exhibits multiple buffering mechanisms, and polyelectrolyte states that shift between aggregated and free forms. We studied the interplay between the aggregation and protonation behavior of 2.5 kDa linear PEI by pH probing, vapor pressure osmometry, dynamic light scattering, and ninhydrin assay. Our results indicate that: At neutral pH, the PEI chains are associated and the addition of NaCl initially reduces and then increases the extent of association.The aggregate form is uncollapsed and co-exists with the free chains.PEI buffering occurs due to continuous or discontinuous charging between stalled states.Ninhydrin assay tracks the number of unprotonated amines in PEI.The size of PEI-DNA complexes is not significantly affected by the free vs. aggregated state of the PEI polymer. Despite its simple chemical structure, linear PEI displays intricate solution dynamics, which can be harnessed for environment-sensitive biomaterials and for overcoming current challenges with DNA delivery. PMID- 27685845 TI - Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome. AB - CONTEXT: Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis. OBJECTIVES: To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS. DESIGN: Experimental study. SETTING: University hospital. SUBJECTS: 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls. INTERVENTIONS: Subjects ingested a liquid meal after fasting >=10 hours. MAIN OUTCOME MEASURES: Leptin and BDNF levels in plasma extracted before ingestion and 30', 60', and 120' after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60' and 120' after ingestion. RESULTS: Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05). Leptin was higher in PWS patients than in controls at all time points (p<0.001). PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65-0.94). In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13-0.9). Postprandial leptin patterns did no differ among genetic subtypes. CONCLUSIONS: Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors. PMID- 27685847 TI - Asarone from Acori Tatarinowii Rhizoma Potentiates the Nerve Growth Factor Induced Neuronal Differentiation in Cultured PC12 Cells: A Signaling Mediated by Protein Kinase A. AB - Acori Tatarinowii Rhizoma (ATR), the rhizome of Acorus tatarinowii Schott, is being used clinically to treat neurological disorders. The volatile oil of ATR is being considered as an active ingredient. Here, alpha-asarone and beta-asarone, accounting about 95% of ATR oil, were evaluated for its function in stimulating neurogenesis. In cultured PC12 cells, application of ATR volatile oil, alpha asarone or beta-asarone, stimulated the expression of neurofilaments, a bio marker for neurite outgrowth, in a concentration-dependent manner. The co treatment of ATR volatile oil, alpha-asarone or beta-asarone, with low concentration of nerve growth factor (NGF) potentiated the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitors, H89 and KT5720, in cultures blocked the ATR-induced neurofilament expression, as well as the phosphorylation of cAMP-responsive element binding protein (CREB). In the potentiation of NGF-induced signaling in cultured PC12 cells, alpha-asarone and beta-asarone showed synergistic effects. These results proposed the neurite-promoting asarone, or ATR volatile oil, could be useful in finding potential drugs for treating various neurodegenerative diseases, in which neurotrophin deficiency is normally involved. PMID- 27685848 TI - Fluid composition and acute kidney injury. AB - PURPOSE OF REVIEW: To describe recent advances in the understanding of the role of fluid composition in renal outcomes in critically ill patients. RECENT FINDINGS: The debate on fluid composition is now focused in a pragmatic discussion on fluid electrolyte composition. The resurgence of this debate was propelled by several observational studies that suggested that balanced (i.e., low chloride) solutions were associated with less acute kidney injury in critically ill patients. Nevertheless, a cluster randomized trial failed to show any benefit of balanced solutions. This trial, however, may have failed to detect an effect because of low global illness severity and little fluid infused. If balanced solutions are to be associated with less acute kidney injury, it will probably be in high risk, aggressively resuscitated patients. Additionally, the causal loop involving unbalanced solution infusion, induction of hyperchloremia and acute kidney injury is yet to be closed. Other factors, such as buffer type, speed of infusion and temperature, among others, may also be important. SUMMARY: Recent evidence suggests that crystalloid fluid composition matters and can influence renal outcomes in critically ill patients. Further studies should assess the impact and cost-efficiency of balanced solutions in the context of high-risk scenarios. PMID- 27685849 TI - Family-centered outcomes during and after critical illness: current outcomes and opportunities for future investigation. AB - PURPOSE OF REVIEW: Family-centered outcomes during and after critical illness assess issues that are most important to family members. An understanding of family-centered outcomes is necessary to support the provision of family-centered care and to foster development of interventions to improve care and communication in the ICU. RECENT FINDINGS: Current family-centered outcomes in critical care include satisfaction with care, including end-of-life care, symptoms of psychological distress, and health-related quality of life. Novel measures include assessments of decisional conflict, decision regret, therapeutic alliance, and caregiver burden, as well as positive adaptations and resilience. SUMMARY: Critical illness places a significant burden on family members. A wide variety of family-centered outcomes are available to guide improvements in care and communication. Future research should focus on developing sensitive and responsive measures that capture key elements of the family member experience during and after critical illness. PMID- 27685850 TI - Genes mirror migrations and cultures in prehistoric Europe-a population genomic perspective. AB - Genomic information from ancient human remains is beginning to show its full potential for learning about human prehistory. We review the last few years' dramatic finds about European prehistory based on genomic data from humans that lived many millennia ago and relate it to modern-day patterns of genomic variation. The early times, the Upper Paleolithic, appears to contain several population turn-overs followed by more stable populations after the Last Glacial Maximum and during the Mesolithic. Some 11000 years ago the migrations driving the Neolithic transition start from around Anatolia and reach the north and the west of Europe millennia later followed by major migrations during the Bronze Age. These findings show that culture and lifestyle were major determinants of genomic differentiation and similarity in pre-historic Europe rather than geography as is the case today. PMID- 27685853 TI - Error in Author Name Tagging. PMID- 27685851 TI - The joint contribution of maternal history of early adversity and adulthood depression to socioeconomic status and potential relevance for offspring development. AB - BACKGROUND: We examined the interactive effects of maternal childhood adversity and later adulthood depression on subsequent socioeconomic status (SES). METHODS: Our community sample ranged from 230 to 243 mothers (across measures) drawn from a prospective, longitudinal cohort study. Maternal childhood adversity scores were derived using an integrated measure derived from the Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Index (PBI). Maternal depression was measured in the prenatal period with the Center for Epidemiologic Studies Depression Scale (CES-D). SES measures included maternal highest level of education and family income as obtained prenatally. RESULTS: The analyses yielded significant interaction effects between maternal childhood adversity and prenatal depression that predicted income, prenatally. Women who reported higher levels of childhood adversity combined with higher levels of self-reported depressive symptoms were significantly more likely to live in low SES environments. Results also showed that level of education was predicted by childhood adversity independent of maternal symptoms of depression. CONCLUSION: The results suggest that SES is influenced by a life course pathway that begins in childhood and includes adversity-related mental health outcomes. Since child health and development is influenced by both maternal mental health and SES, this pathway may also contribute to the intergenerational transmission of the risk for psychopathology in the offspring. The results also emphasize the importance of studying potential precursors of low SES, a well-documented environmental risk factor for poor developmental outcomes in the offspring. PMID- 27685852 TI - Age effect on autobiographical memory specificity: A study on autobiographical memory specificity in elderly survivors of childhood trauma. AB - BACKGROUND AND OBJECTIVES: Post-traumatic stress disorder (PTSD) is accompanied by altered autobiographical memories (AM) of the traumatic incident itself as well as of non-trauma-related events. Several studies have shown that trauma exposed individuals developing PTSD have a reduced capacity to access specific past events that are not related to the traumatic event compared to those who do not develop PTSD. However, one study including a group of elderly adults did not find significant differences in AM between PTSD and non-PTSD participants. The present study investigated whether PTSD is associated with impaired AM of trauma related and non-trauma-related memories in the elderly. METHOD: Forty-four elderly participants, displaced during childhood from former German territories after the end of World War II (WWII), were examined. This group comprised 19 participants with and 25 participants without PTSD. These participants were compared to 23 non-traumatized non-displaced elderly participants. RESULTS: PTSD, non-PTSD and non-traumatized participants do not differ significantly in their ability to recall specific memories of their past. Moreover, participants with PTSD did not recall more trauma-related memories than non-PTSD participants. LIMITATIONS: The traumatized participants reached for assessment might represent the most resilient individuals, which might constrain generalizability of our results to other trauma populations. CONCLUSIONS: This study confirms preliminary evidence that PTSD is not associated with AM impairment in the elderly. We suggest that aging may alter the relationship between trauma and AM impairment in traumatized participants with PTSD, which need to be confirmed by longitudinal studies. PMID- 27685854 TI - Niche Partitioning among Mesocarnivores in a Brazilian Wetland. AB - We investigated the home range size, habitat selection, as well as the spatial and activity overlap, of four mid-sized carnivore species in the Central Pantanal, Mato Grosso do Sul, Brazil. From December 2005 to September 2008, seven crab-eating foxes Cerdocyon thous, seven brown-nosed coatis Nasua nasua, and six ocelots Leopardus pardalis were radio-collared and monitored. Camera trap data on these species were also collected for the crab-eating raccoon Procyon cancrivorus. We hypothesized that there would be large niche differentiation in preferred habitat-type or active period between generalist species with similar diet, and higher similarity in habitat-type or activity time between the generalist species (crab-eating foxes and coatis) and the more specialized ocelot. Individual home ranges were estimated using the utilization distribution index (UD- 95% fixed Kernel). With data obtained from radio-collared individuals, we evaluated habitat selection using compositional analysis. Median home range size of ocelots was 8 km2. The proportion of habitats within the home ranges of ocelots did not differ from the overall habitat proportion in the study area, but ocelots preferentially used forest within their home range. The median home range size of crab-eating foxes was 1.4 km2. Foxes showed second-order habitat selection and selected savanna over shrub-savanna vegetation. The median home range size for coati was 1.5 km2. Coati home ranges were located randomly in the study area. However, within their home range, coatis occurred more frequently in savanna than in other vegetation types. Among the four species, the overlap in activity period was the highest (87%) between ocelots and raccoons, with the least overlap occurring between the ocelot and coati (25%). We suggest that temporal segregation of carnivores was more important than spatial segregation, notably between the generalist coati, crab-eating fox and crab-eating raccoon. PMID- 27685855 TI - Tumor-Infiltrating Macrophages in Post-Transplant, Relapsed Classical Hodgkin Lymphoma Are Donor-Derived. AB - Tumor-associated inflammatory cells in classical Hodgkin lymphoma (CHL) typically outnumber the neoplastic Hodgkin/Reed-Sternberg (H/RS) cells. The composition of the inflammatory infiltrate, particularly the fraction of macrophages, has been associated with clinical behavior. Emerging work from animal models demonstrates that most tissue macrophages are maintained by a process of self-renewal under physiologic circumstances and certain inflammatory states, but the contribution from circulating monocytes may be increased in some disease states. This raises the question of the source of macrophages involved in human disease, particularly that of CHL. Patients with relapsed CHL following allogeneic bone marrow transplant (BMT) provide a unique opportunity to begin to address this issue. We identified 4 such patients in our archives. Through molecular chimerism and/or XY FISH studies, we demonstrated the DNA content in the post-BMT recurrent CHL was predominantly donor-derived, while the H/RS cells were derived from the patient. Where possible to evaluate, the cellular composition of the inflammatory infiltrate, including the percentage of macrophages, was similar to that of the original tumor. Our findings suggest that the H/RS cells themselves define the inflammatory environment. In addition, our results demonstrate that tumor associated macrophages in CHL are predominantly derived from circulating monocytes rather than resident tissue macrophages. Given the association between tumor microenvironment and disease progression, a better understanding of macrophage recruitment to CHL may open new strategies for therapeutic intervention. PMID- 27685858 TI - Working with Commercially Available Quantum Dots for Immunofluorescence on Tissue Sections. AB - Quantum dots are semiconductor fluorescent nanocrystals that exhibit excellent characteristics compared with more commonly used organic fluorescent dyes. For many years quantum dot conjugated products have been available in multiple forms for fluorescence imaging of tissue sections under the trademark name Qdot(r). They have much increased brightness, narrow emission spectrum, large Stokes shift and photostability compared with conventional organic fluorescent dyes, which together make them the fluorophores of choice for demanding requirements. Vivid Qdots are recent replacements for original Qdots, modified to improve brightness, however this has affected the fluorescence stability in commonly used conditions for immunohistochemistry. We present here our investigation of the stability of original and Vivid Qdots in solution and in immunohistochemistry, highlight the potential pitfalls and propose a protocol for stable and reliable multiplex staining with current commercially available original and Vivid Qdots. PMID- 27685856 TI - Characterization of Botrytis cinerea negative-stranded RNA virus 1, a new mycovirus related to plant viruses, and a reconstruction of host pattern evolution in negative-sense ssRNA viruses. AB - The molecular characterization of a novel negative single-stranded RNA virus infecting the plant pathogenic fungus Botrytis cinerea is reported here. Comparison of the sequence of Botrytis cinerea negative-stranded RNA virus 1 (BcNSRV-1) showed a strong identity with RNA dependent RNA polymerases (RdRps) of plant pathogenic emaraviruses and tospoviruses. We have also found all the molecular signatures present in the RdRp of the genus Emaravirus and in other genera of family Bunyaviridae: the conserved TPD triplet and RY dinucleotide, the three basic residues in premotif A and the conserved motifs A, B, C, D, and E. Our results showed that BcNSRV-1 is phylogenetically close to members of the genus Emaravirus and of the family Bunyaviridae, and an ancestral state reconstruction using the conserved RdRp motifs of type members of each family of (-)ssRNA viruses indicated that BcNSRV-1 could possibly derive from an invertebrate and vertebrate-infecting virus. PMID- 27685859 TI - Direction of the Relationship Between Acceptance of Illness and Health-Related Quality of Life in Chronic Heart Failure Patients. AB - BACKGROUND: This study provides an in-depth insight into the relationships between illness acceptance and health-related quality of life (HRQoL) of chronic heart failure (CHF) patients. Although HRQoL is a well-established endpoint in CHF, little is known on illness acceptance in this group. AIMS: The aim of this study is to critically reconsider the direction of a relationship between HRQoL and illness acceptance in CHF patients. METHODS: The study included 204 patients (160 men and 44 women; mean age, 63 +/- 11 years) with at least 6-month clinical evidence of CHF corresponding to New York heart Association (NYHA) classes I to IV. All the patients were examined with the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and Acceptance of Illness Scale (AIS). RESULTS: Univariate analysis showed that the level of illness acceptance correlated inversely with patient age, and the level of HRQoL decreased with the severity of CHF (NYHA class). A relationship between illness acceptance and HRQoL was analyzed by structural equation modeling. Model 1 was based on the assumption that HRQoL is modulated by illness acceptance, and model 2 tested the opposite relationship. Both models included patient age and NYHA class as extrinsic determinants of AIS and MLHFQ scores, respectively. Model 2 proved to be well fitted (chi [df = 2] = 3.22, P = .20, root-mean-square error of approximation = 0.055). Scores on the AIS correlated inversely with age (bage->AIS = -0.15, SE = 0.05, P = .002) and HRQoL (bQoL->AIS = -0.15, SE = 0.02, P < .001), and an increase in NYHA class was reflected by an increase in HRQoL scores (bNYHA->QoL = 5.75, SE = 1.97, P = .004). CONCLUSION: Patients with CHF may not accept their disease due to deteriorated HRQoL. As a result, they may be uninvolved in the therapeutic process, which leads to exacerbation of CHF, further deterioration of HRQoL, and inability to accept the illness. PMID- 27685860 TI - Recruitment Strategies and Costs Associated With Enrolling People With Insomnia and High Blood Pressure Into an Online Behavioral Sleep Intervention: A Single Site Pilot Study. AB - BACKGROUND: Recruitment in clinical research is a common challenge and source of study failure. The reporting of recruitment methods and costs in hypertension trials is limited especially for smaller, single-site trials, online intervention trials, and trials using newer online recruitment strategies. OBJECTIVE: The aims of this study are to describe and examine the feasibility of newer online-e-mail recruitment strategies and traditional recruitment strategies used to enroll participants with insomnia and high blood pressure into an online behavioral sleep intervention study (Sleeping for Heart Health). METHODS: The 16 online-e mail-based and traditional recruitment strategies used are described. Recruitment strategy feasibility was examined by study interest and enrollee yields, conversion rates, and costs (direct, remuneration, labor, and cost per enrollee). RESULTS: From August 2014 to October 2015, 183 people were screened and 58 (31.7%) enrolled in the study (51.1 +/- 12.9 years, 63.8% female, 72.4% African American, 136 +/- 12/88 +/- 7 mm Hg, 87.9% self-reported hypertension, 67.2% self reported antihypertensive medication use). The recruitment strategies yielding the highest enrollees were the university hospital phone waiting message system (25.4%), Craigslist (22.4%), and flyers (20.3%) at a per enrollee cost of $42.84, $98.90, and $128.27, respectively. The university hospital phone waiting message system (55.6%) and flyers (54.5%) had the highest interested participant to enrolled participant conversion rate of all recruitment strategies. CONCLUSION: Approximately 70% of all enrolled participants were recruited from the university hospital phone waiting message system, Craigslist, or flyers. Given the recruitment challenges that most researchers face, we encourage the documenting, assessing, and reporting of detailed recruitment strategies and associated recruitment costs so that other researchers may benefit. PMID- 27685862 TI - Protocol for Data Collection and Analysis Applied to Automated Facial Expression Analysis Technology and Temporal Analysis for Sensory Evaluation. AB - We demonstrate a method for capturing emotional response to beverages and liquefied foods in a sensory evaluation laboratory using automated facial expression analysis (AFEA) software. Additionally, we demonstrate a method for extracting relevant emotional data output and plotting the emotional response of a population over a specified time frame. By time pairing each participant's treatment response to a control stimulus (baseline), the overall emotional response over time and across multiple participants can be quantified. AFEA is a prospective analytical tool for assessing unbiased response to food and beverages. At present, most research has mainly focused on beverages. Methodologies and analyses have not yet been standardized for the application of AFEA to beverages and foods; however, a consistent standard methodology is needed. Optimizing video capture procedures and resulting video quality aids in a successful collection of emotional response to foods. Furthermore, the methodology of data analysis is novel for extracting the pertinent data relevant to the emotional response. The combinations of video capture optimization and data analysis will aid in standardizing the protocol for automated facial expression analysis and interpretation of emotional response data. PMID- 27685861 TI - Perceptions of Disease-Related Stress: A Key to Better Understanding Patient Reported Outcomes Among Survivors of Congenital Heart Disease. AB - BACKGROUND: Disease-related stressors for survivors of congenital heart disease (CHD) have been qualitatively described but not quantified nor examined in relationship to important patient-reported outcomes (PROs). OBJECTIVE: The aims of this study are to (1) identify the types and degree of disease-related stress experienced by CHD survivors based on age, functional status, and sex, (2) examine differences in stress and PROs by age, functional status, and sex, and (3) determine the unique contribution of perceived stress to variability in PROs. METHODS: A cross-sectional study of 173 adolescents and emerging and young adults who were recruited from both pediatric and adult CHD clinics was conducted. Participants rated the degree to which they found various aspects of CHD stressful and completed PROs of health-related quality of life and emotional distress. Differences in perceptions of stress across predictors were determined using analyses of variance and chi analyses. The relative contribution of perceived stress predicting PROs was examined using stepwise linear regression. RESULTS: Two items emerged as being stressful for almost half of the sample, including concerns about future health and having scars or other signs of medical procedures. Adolescents reported less perceived stress than emerging or young adults, and survivors with even mild functional limitations reported higher perceived stress than did those without any symptoms. Perceptions of stress significantly contributed to variability in PROs above and beyond other predictors and was the only variable to explain unique variance in emotional distress. CONCLUSIONS: Having even mild functional impairment may have significant deleterious consequences on PROs via increased perceptions of stress. Stress may be modifiable using cognitive behavioral therapy. PMID- 27685864 TI - Classifying and Standardizing Panfacial Trauma With a New Bony Facial Trauma Score. AB - Importance: The practice of facial trauma surgery would benefit from a useful quantitative scale that measures the extent of injury. Objective: To develop a facial trauma scale that incorporates only reducible fractures and is able to be reliably communicated to health care professionals. Design and Setting: A cadaveric tissue study was conducted from October 1 to 3, 2014. Ten cadaveric heads were subjected to various degrees of facial trauma by dropping a fixed mass onto each head. The heads were then imaged with fine-cut computed tomography. A Bony Facial Trauma Scale (BFTS) for grading facial trauma was developed based only on clinically relevant (reducible) fractures. The traumatized cadaveric heads were then scored using this scale as well as 3 existing scoring systems. Regression analysis was used to determine correlation between degree of incursion of the fixed mass on the cadaveric heads and trauma severity as rated by the scoring systems. Statistical analysis was performed to determine correlation of the scores obtained using the BFTS with those of the 3 existing scoring systems. Scores obtained using the BFTS were not correlated with dentition (95% CI, -0.087 to 1.053; P = .08; measured as absolute number of teeth) or age of the cadaveric donor (95% CI, -0.068 to 0.944; P = .08). Main Outcome Measures: Facial trauma scores. Results: Among all 10 cadaveric specimens (9 male donors and 1 female donor; age range, 41-87 years; mean age, 57.2 years), the facial trauma scores obtained using the BFTS correlated with depth of penetration of the mass into the face (odds ratio, 4.071; 95% CI, 1.676-6.448) P = .007) when controlling for presence of dentition and age. The BFTS scores also correlated with scores obtained using 3 existing facial trauma models (Facial Fracture Severity Scale, rs = 0.920; Craniofacial Disruption Score, rs = 0.945; and ZS Score, rs = 0.902; P < .001 for all 3 models). In addition, the BFTS was found to have excellent interrater reliability (0.908; P = .001), which was similar to the interrater reliability of the other 3 tested trauma scales. Scores obtained using the BFTS were not correlated with dentition (odds ratio, .482; 95% CI, -0.087 to 1.053; P = .08; measured as absolute number of teeth) or age of the cadaveric donor (odds ratio, .436; 95% CI, -0.068 to 0.944; P = .08). Conclusions and Relevance: Facial trauma severity as measured by the BFTS correlated with depth of penetration of the fixed mass into the face. In this study, the BFTS was clinically relevant, had high fidelity in communicating the fractures sustained in facial trauma, and correlated well with previously validated models. Level of Evidence: NA. PMID- 27685863 TI - Genome-Wide Identification and Expression Analysis of MRLK Family Genes Associated with Strawberry (Fragaria vesca) Fruit Ripening and Abiotic Stress Responses. AB - Malectin-like domain-containing receptor-like kinases (MRLK) constitute a large and divergent family of proteins in plants; however, little is known about the role of MRLKs in fruit growth and development. In this study, we characterized MRLK family genes in diploid strawberry, Fragaria vesca. Based on an analysis of malectin-like domain and a search in the strawberry genome and NCBI database, we identified 62 FvMRLKs in the strawberry genome, and classified these genes into six subfamilies with distinct malectin domains in the extracellular regions of the encoded proteins. Gene expression analysis indicated that more than 80% of the FvMRLKs were expressed in various tissues, with higher levels in roots than in other organs. Thirty-three FvMRLKs were found to be expressed in fruits during the early stages of development, and over 60% of these exhibited dramatic decreases in expression during fruit growth and development. Moreover, the expression of some FvMRLKs was sensitive to both environmental and internal cues that play critical roles in regulating strawberry fruit development and ripening. Collectively, this study provides valuable insight into the FvMRLKs gene family and its role in regulating strawberry fruit development and ripening. PMID- 27685865 TI - Reproductive health indicators and fetal medicine - many things will change. AB - Reproductive epidemiologists study disease outcomes over three time periods: (i) from conception, or before, to birth, (ii) from birth to death and (iii) from death and into the next generations. They have traditionally been short of data from the time of conception to birth, and we use data at birth to estimate fetal growth or the incidence of congenital malformations. Although we are interested in incidence data for defects that start early in gestation, we have to use prevalence data at birth. Cumulative incidence will only be similar to prevalence at birth given no competing risks - or no fetal death after the onset of the lesion. Routinely use of ultrasound methods in fetal medicine will change our monitoring of structural birth defects. We may now be able to link exposures to events with the right time sequence, for example on fetal growth deviations and get better data on fetal deaths also for twins and triplets. The scientific challenges will mainly come from induced abortions following ultrasound examinations. Ultrasound data from the time of pregnancy will be of crucial importance for studies on fetal programming or "developmental origins of health and disease" (DOHaD). In humans, babies that are small at birth have an increased risk of, eg, cardiovascular disease, as shown by DJ Barker in the 1980s (1), but this association is probably not a direct consequence of the low birth weight but rather caused by external or internal exposures during fetal life. DOHaD studies that use outcomes at birth, including weight, as exposures or intermediates may be biased. One notorious example is the apparent protective effect of smoking on the mortality of children with a low birth weight (2). This bias, partly related to collider stratification bias, is potentially less important in studies using direct ultrasound assessments. The risk of reverse causation may also be reduced in longitudinal studies based on ultrasound data. Fetal ultrasound examinations are also done to detect fetal structural abnormalities in order to start early treatment or terminate an effected pregnancy if that is permitted and requested by the parents. This change in timing and validity of determining congenital abnormalities (CA) will have substantial consequences for our monitoring of CA over time. Most of the existing monitoring systems are based on measuring prevalence of CA at time of birth, often allowing for a time period of detection from months to years since some of the CA are not detected at birth. They may be detected by ultrasound during gestation, but even for CA detectable in gestational weeks 20-24 and at birth, the sensitivity and specificity of times of diagnosing may differ so much that the measures are not comparable. Furthermore, the time from ultrasound to birth is sometimes interrupted by late fetal deaths and some of these deaths may be induced on indication. In any case, it will be difficult to reestablish long-term monitoring trends by applying birth correcting factors that will differ by the type of CA. We probably have to accept that long term time trends need years to be reestablished and will have to be based on updated diagnostic facilities that will change over time. It may be difficult to spot increases in the incidence of CA in the future. An increase could be real or related to better diagnostic facilities operating in the time period from conception to birth. Fetal medicine will sometimes make it possible to study causes and events in the proper time sequence, which is important since a cause has to precede an event as the only sine qua non causal criteria. Measurements of recurrence "risks" of CA in families have always been complicated. It is well known that several CA have a tendency to be repeated in a subsequent pregnancy, most likely related to genetic factors or other time stable environmental exposures. Better diagnostic facilities with an option for an induced abortion may encourage high-risk parents to try to become pregnant and this may affect estimates of recurrence risk. In any case, calculating recurrence risk for newborns following siblings with the CA in question will probably no longer work (maybe it never worked) since the desire to reach a given family size depends on many factors, including the perceived risk of a CA. Access to prenatal diagnostic data may therefore well produce data closer to recurrence risk than data recorded at the time of birth. Pediatrics and Perinatal Epidemiology recently published a series of papers initiated by Olga Basso (3, 4) addressing in part the problem of moving from time scale one (starting at conception) to time scale two (starting at birth). Part of the addressed problems relate to a lack of options for starting observations on causal factors at the onset of exposure or, at best, before exposure. If that exposure happens early in fetal life, outcomes will be complicated by fetal deaths that probably end observation for >=30% of subjects. That equals mortality rates we see for >=95-year-olds or equals a cumulative death risk seen for newborns from birth to >=65 years of age. If the exposure of interest is related to fetal death that opens up for strong collider stratification bias and selection when we condition on survival in our analyses for observations at the beginning of the second time scale (5). A negative association on that time scale need not reflect "prevention" in any sense other than suicides early in life will prevent later cancer deaths. It is difficult to imagine a counterfactual comparison to an exposed had he/she not been exposed and had survived fetal life. Those who were susceptible did not all survive. If we study fetal programming of adult diseases, we have to "condition on birth" in our studies, but we should be aware of the selection bias that follows. Fetal medicine will in many ways produce better data or data we never have had before, but it will change the conditions in many aspects of reproductive epidemiology. The main advantage in analytical epidemiology is to get the time sequence right from exposure to outcome to avoid the problem of reverse causation and to do proper mediation analyses. Conflict of interest The authors declare no conflicts of interest. PMID- 27685866 TI - Folic Acid-Metabolizing Enzymes Regulate the Antitumor Effect of 5-Fluoro-2' Deoxyuridine in Colorectal Cancer Cell Lines. AB - In colorectal cancer chemotherapy, the current standard of care includes combination therapy with 5-fluorouracil (5-FU) and leucovorin (LV). However, the factors that determine the LV-mediated enhancement of 5-FU antitumor activity are not fully understood. Therefore, we investigated the roles of thymidine synthase (TYMS), folate receptor 1 (FOLR1), dihydrofolate reductase (DHFR), phosphoribosylglycinamide formyltransferase (GART), methylenetetrahydrofolate dehydrogenase (MTHFD1), and methylenetetrahydrofolate reductase (MTHFR) in LV mediated enhancement of 5-fluoro-2'-deoxyuridine (FdUrd) cytotoxicity in vitro as a model of 5-FU antitumor activity. These genes were downregulated in DLD-1 and HCT116 human colorectal cancer cells by using small-interfering RNA. Reduced expression of TYMS mRNA significantly increased FdUrd cytotoxicity by 100- and 8.3-fold in DLD-1 and HCT116 cells, respectively. In contrast, reducing the expression of FOLR1, DHFR, GART, MTHFD1, and MTHFR decreased FdUrd cytotoxicity by 2.13- to 12.91-fold in DLD-1 cells and by 3.52- to 10.36-fold in HCT116 cells. These results demonstrate that folate metabolism is important for the efficacy of FdUrd. Overall, the results indicate that it is important to clarify the relationship between folate metabolism-related molecules and 5-FU treatment in order to improve predictions of the effectiveness of 5-FU and LV combination therapy. PMID- 27685867 TI - Doping-Induced Absorption Bands in P3HT: Polarons and Bipolarons. AB - In this work, we focus on the formation of different kinds of charge carriers such as polarons and bipolarons upon p-type doping (oxidation) of the organic semiconductor poly(3- hexylthiophene-2,5-diyl) (P3HT). We elucidate the cyclic voltammogram during oxidation of this polymer and present spectroscopic changes upon doping in the UV/Vis/near-IR range as well as in the mid-IR range. In the low-oxidation regime, two absorption bands related to sub-gap transitions appear, one in the UV/Vis range and another one in the mid-IR range. The UV/Vis absorption gradually decreases upon further doping while the mid-IR absorption shifts to lower energy. Additionally, electron paramagnetic resonance (EPR) measurements are performed, showing an increase of the EPR signal up to a certain doping level, which significantly decreases upon further doping. Furthermore, the absorption spectra in the UV/Vis range are analyzed in relation to the morphology (crystalline vs. amorphous) by using theoretical models. Finally, the calculated charge carriers from cyclic voltammogram are linked together with optical transitions as well as with the EPR signals upon p-type doping. We stress that our results indicate the formation of polarons at low doping levels and the existence of bipolarons at high doping levels. The presented spectroscopic data are an experimental evidence of the formation of bipolarons in P3HT. PMID- 27685869 TI - A Novel Hybrid Firefly Algorithm for Global Optimization. AB - Global optimization is challenging to solve due to its nonlinearity and multimodality. Traditional algorithms such as the gradient-based methods often struggle to deal with such problems and one of the current trends is to use metaheuristic algorithms. In this paper, a novel hybrid population-based global optimization algorithm, called hybrid firefly algorithm (HFA), is proposed by combining the advantages of both the firefly algorithm (FA) and differential evolution (DE). FA and DE are executed in parallel to promote information sharing among the population and thus enhance searching efficiency. In order to evaluate the performance and efficiency of the proposed algorithm, a diverse set of selected benchmark functions are employed and these functions fall into two groups: unimodal and multimodal. The experimental results show better performance of the proposed algorithm compared to the original version of the firefly algorithm (FA), differential evolution (DE) and particle swarm optimization (PSO) in the sense of avoiding local minima and increasing the convergence rate. PMID- 27685868 TI - The cell division control protein 42-Src family kinase-neural Wiskott-Aldrich syndrome protein pathway regulates human proplatelet formation. AB - : Essentials The role of the cytoskeleton during megakaryocyte differentiation was examined. Human megakaryocytes are derived from in vitro cultured CD34+ cells. Cell division control protein 42 (CDC42) positively regulates proplatelet formation (PPF). Neural Wiskott-Aldrich syndrome protein, the main effector of CDC42 with Src positively regulates PPF. SUMMARY: Background Cytoskeletal rearrangements are essential for platelet release. The RHO small GTPase family, as regulators of the actin cytoskeleton, play an important role in proplatelet formation (PPF). In the neuronal system, CDC42 is involved in axon formation, a process that combines elongation and branching as for PPF. Objective To analyze the role of CDC42 and its effectors of the Wiskott-Aldrich syndrome protein (WASP) family in PPF. Methods Human megakaryocytes (MKs) were obtained from CD34+ cells. Inhibition of CDC42 in MKs was performed with the chemical inhibitor CASIN or with an active or a dominant-negative form of CDC42. The knock-down of N-WASP was obtained with a small hairpin RNA strategy Results Herein, we show that CDC42 activity increased during MK differentiation. The use of the chemical inhibitor CASIN or of an active or a dominant-negative form of CDC42 demonstrated that CDC42 positively regulated PPF in vitro. We determined that N-WASP, but not WASP, regulated PPF. We found that N-WASP knockdown led to a marked decrease in PPF, owing to a defect in the demarcation membrane system (DMS). This was associated with RHOA activation, and a concomitant augmentation in the phosphorylation of mysosin light chain 2. Phosphorylation of N-WASP, creating a primed form of N WASP, increased during MK differentiation. Phosphorylation inhibition by two Src family kinase inhibitors decreased PPF. Conclusions We conclude that N-WASP positively regulates DMS development and PPF, and that the Src family kinases in association with CDC42 regulate PPF through N-WASP. PMID- 27685870 TI - Comparison of laparoscopic major hepatectomy with propensity score matched open cases from the National Clinical Database in Japan. AB - BACKGROUND: The National Clinical Database (NCD) in Japan is a nationwide registry that collects the data of more than 1,200,000 surgical cases annually from over 3,500 hospitals. Based on the NCD data, this study compared the perioperative outcomes of major laparoscopic liver resection (LLR) with those of major open liver resection (OLR) using the propensity score matching method. METHODS: We collected data on 15,191 major hepatectomy cases (929 major LLR cases and 14,262 major OLR cases), and investigated the short-term outcomes in well matched groups. RESULTS: In the LLR group, 30-day mortality, in-hospital mortality, and operative mortality were 0.9%, 1.7%, and 1.7% respectively. The mean blood loss in the LLR group (865.4 +/- 1,148.2 ml) was significantly less than in the OLR group (1,053.8 +/- 1,176.6 ml), and the median postoperative hospital stay for the LLR patients (21.37 +/- 19.71 days) was significantly shorter than for the OLR patients (26.25 +/- 24.53 days). The complication rate in the LLR group (16.4%) was significantly lower than that in the OLR group (23.5%). CONCLUSION: LLR in selected patients is currently safely performed as well as OLR even in patients requiring major hepatectomy, associated with less blood loss, shorter hospital stays, and fewer complications. PMID- 27685871 TI - Healthcare-professional patients' conceptions of being ill and hospitalised - a phenomenographic study. AB - AIMS AND OBJECTIVES: To describe the variation of conceptions of being ill and hospitalised, from the perspective of healthcare-professional patients. BACKGROUND: Previous literature focuses on either physicians' or nurses' experiences of being a patient, without aiming at determining a variation of ways of understanding that phenomena. Nor have we been able to identify any study reporting other healthcare professionals' experiences. DESIGN: This study has an inductive descriptive design. METHODS: Qualitative interviews with healthcare professionals (n = 16), who had been hospitalised for at least two days. Phenomenographic data analysis was conducted. RESULTS: The feelings of security were based on knowledge, insight and trust, and acceptance of the healthcare system. Being exposed and totally dependent due to illness provoked feelings of vulnerability and insecurity. The patients used their knowledge to achieve participation in the care. The more severe they perceived their illness to be, the less they wanted to participate and the more they expressed a need for being allowed to surrender control. The patients' ideal picture of care was sometimes disrupted, and based on their experience, they criticised care and made suggestions that could contribute to general care improvements. CONCLUSIONS: Healthcare-professional patients have various conceptions of being ill and hospitalised. Based on the general nature of the many needs expressed, we believe that the insights provided in this study can be transferred so as to also be valid for lay patients. Possibly, an overhaul of routines for discharge planning and follow-up, and adopting a person-centred approach to care, can resolve some of the identified shortcomings. RELEVANCE TO CLINICAL PRACTICE: The results can be used for the purpose of developing knowledge for healthcare professions and for educational purposes. PMID- 27685873 TI - A New Hospital for the Children of Ireland. PMID- 27685874 TI - Technical Knockout: When is Traumatic Brain Injury 'just' a Concussion? PMID- 27685875 TI - Car Safety Seat Usage and Selection Among Families Attending University Hospital Limerick. AB - The safest way for children to travel within a car is by provision of a weight appropriate safety-seat. To investigate this, we conducted a cross-sectional study of adult parents who had children under 12 years, and collected information related to: car use, safety-seat legislation, and type of safety-seat employed. Data were reviewed on 120 children from 60 respondents. Ninety-eight (81.7%) children were transported daily by car. Forty-eight (81.4%) respondents were aware that current safety-seat legislation is based on the weight of the child. One hundred and seven (89.9%) children were restrained during travel using a car safety-seat. One hundred and two (96.2%) safety seats were newly purchased, installed in 82.3% (88) cases by family members with installation instructions fully read in 58 (55.2%) cases. Ninety-nine (83.2%) children were restrained using an appropriate safety-seat for their weight. The results show that four out of five families are employing the most appropriate safety-seat for their child, so providing an effective mechanism to reduce car-related injury. However, the majority of safety-seats are installed by family members, which may have child safety consequences. PMID- 27685872 TI - Clinical Pharmacology in Denmark in 2016 - 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality. AB - The Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs. Clinical pharmacologists are active in drug committees both in hospitals and in the primary sector. All clinical pharmacology centres offer a local medicines information service. Some centres have established an adverse drug effect manager function. Only one centre offers a therapeutic drug monitoring service. Clinical pharmacologists are responsible for the toxicological advice at the Danish Poison Information Centre at Bispebjerg University Hospital in the Capital Region. The Department of Clinical Pharmacology at Aarhus University Hospital works closely together with forensic toxicologists and pathologists, covering issues regarding illicit substances, forensic pharmacology, post-mortem toxicology, expert testimony and research. Therapeutic geriatric and psychiatric teach-inns for specialist and junior doctors are among the newest initiatives organized by clinical pharmacologists. Clinical pharmacologists work also in the Danish Medicines Agency and in the Danish pharmaceutical industry, and the latter has in particular a great growth potential for creating new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors) or approximately 12 specialists per one million inhabitants. PMID- 27685877 TI - The Efficacy of Bronchial Thermoplasty for Severe Persistent Asthma: The First National Experience. AB - There is an unmet need for new therapies in severe persistent asthma. Bronchial thermoplasty is a bronchoscopic procedure which employs radiofrequency energy to reduce airway smooth muscle and has been demonstrated to improve symptomatic control in severe persistent asthma in other populations. Seven patients have completed bronchial thermoplasty at a tertiary referral centre in Ireland. Asthma Control Test scores and data on hospitalisations, exacerbations, maintenance corticosteroid requirements, rescue bronchodilator use and peak expiratory flow rate (PEFR) were compared one year before and one year post treatment. Significant improvements were demonstrated in mean Asthma Control Test scores, from 8.9 to 14.7 (p = 0.036). Trends towards improvement were seen in mean hospitalisations (respective values for total in 12 month period 5.0, 0.9; p = 0.059) and PEFR (181.4 l/min, 280 l/min respectively; p = 0.059). These data support the use of bronchial thermoplasty in severe persistent asthma in the Irish population. PMID- 27685876 TI - Attitudes toward Palliative Care and End of Life Issues: A Prospective Survey in Patients with Metastatic Cancer. AB - Palliative care (PC) positively impacts patient outcomes, decreases hospital admissions and improves quality of life. Despite evidence, PC resources are reported as under-utilised. Few studies have explored patient attitudes towards PC. This study evaluated patient attitudes towards PC. It was a prospective study conducted in oncology outpatient clinics. A 26-item questionnaire was distributed to those with metastatic cancer (N = 44). Sixty percent believed PC can make people feel better, 63.4% believed PC is offered when nothing more can be done. Most were unsure or disagreed that opioids are addictive. Eighty percent reported symptom control is more important than prolonging life. Sixty-one percent strongly agreed or agreed that "losing hope makes people die sooner". Although PC was deemed beneficial, a significant relationship exists between familiarity with PC and thinking it is offered when "nothing more can be done". Lack of knowledge about opioids, preference for symptom control over life prolonging measures and the importance of hope were also emphasised. PMID- 27685878 TI - A Prospective Analysis of the Relationship between Chronic Diseases and Adiposity in older adults: Findings from the Lifeways Cross-Generation Cohort Study of a Thousand Families 2001-2014. AB - This study assesses the relationship between body mass index (BMI) and adult chronic diseases (diabetes mellitus type 2 [DM2], cardiovascular diseases [CVD] and cancers), in grandparents in the Lifeways Cross-Generation Cohort Study. BMI was either measured or reported, at baseline or 10-year follow-up, in 1,244 grandparents. Cumulative morbidity data were recorded at baseline, 3 and 10-year follow-up through questionnaires, General Practice note search, or both. Just over 42% of grandparents were overweight and 32.1% obese. In the multivariate analysis BMI showed a strong linear association with both DM2 (ptrend <0.001) and CVD (ptrend <0.001). There were no significant associations with cancers, but case numbers were small. Results were similar for waist circumference. This prospective study presents novel Irish data and confirms other recent Irish cross sectional reports on adiposity and adult chronic disease, highlighting the need for effective health promotion interventions in older adults. PMID- 27685879 TI - Critical Airway Compromise due to a Massive Vagal Schwannoma. AB - We describe the case of a 37-year-old man with a slowly enlarging neck lump and compressive symptoms. He presented to a separate institution 10 years prior where an observational approach was advocated. Following preoperative investigations and embolization, an 11cm vagal schwannoma was excised and vagus nerve was sacrificed. Although conservative management is appropriate for a select patient population, surgical excision is treatment of choice for cervical neurogenic tumours and paraganglionomas and must be considered in young patients or rapidly expanding tumours to avoid compressive symptoms, as in this case. PMID- 27685880 TI - Culture Negative Infective Endocarditits: a Changing Paradigm. AB - Traditionally, the modified Duke's criteria, based primarily on positive blood cultures, is used to diagnose Infective Endocarditis (IE). However, reports demonstrate that 31% of cases are diagnosed as Culture Negative Infective Endocarditis (CNIE)1. Consequently, empiric broad-spectrum antibiotics are prescribed to cover unidentified organisms and, as a result, antibiotic therapy may be compromised. Molecular diagnostic techniques aid with identifying causative organisms in cases of CNIE and we question if the increasing use of such technologies will change the local epidemiology of CNIE. We present the first case of Tropheryma whipplei Infective Endocarditis (TWIE) reported in Ireland. PMID- 27685882 TI - Band Heterotopia: An Unusual Cause of Seizures. PMID- 27685881 TI - Palliative Subcutaneous Terbutaline Infusion in Severe Asthma. AB - Continuous subcutaneous infusion of terbutaline (CSIT) has been shown to improve asthma control. As an adjunct to standard asthma pharmacotherapy, 3-12mg/day of CSIT can stabilise asthmatic symptoms, reduce hospitalisations and reduce corticosteroid need1,2. Asthmatics who demonstrate a wide diurnal variability in their peak-flows (>40%), termed brittle asthmatics tend to benefit the most from this therapy3. CSIT can have adverse effects and should only be used in specialist respiratory centres. PMID- 27685883 TI - Medical Student and General Practitioner Perceptions of Challenges in General Practice in Ireland. AB - In Ireland, there is a critical shortage in the supply of general practitioners that is projected to worsen. One possible response is to attempt to increase medical student interest in pursuing a career in general practice. Our study aimed to describe the challenges that medical students and general practitioners perceive in the field of general practice. A cross-sectional online survey of 96 medical students (10.5% response rate) enrolled at the National University of Ireland, Galway and 35 general practitioners (24.6% response rate) who attended the Vasco da Gama Movement (VdGM) Forum in February 2015. VdGM is the WONCA Europe Network for new and future general practitioner. The most commonly perceived challenges included remuneration, stress, access to imaging, respect from fellow medical professionals, treating the ageing population, and complexity of patients. These challenges were also generally rated as of high priority. There was large congruence between students and practitioners as to the challenges and what priority they represented. Of medical student participants, 18% indicated that general practice was their career of choice. Medical students and general practitioner have identified several challenges in the Irish general practice setting. Addressing these concerns is crucial to attract and retain future general practitioners. PMID- 27685884 TI - Beware of Non-Traumatic Chylothorax. PMID- 27685885 TI - Clinical Decision Rules for CT in Minor Head Injury. PMID- 27685886 TI - Hand in Hand: The Activity of a Soft Tissue Trauma Clinic in a Tertiary Referral Centre and its Association with Economic Prosperity. PMID- 27685887 TI - Basic Signaling in Cardiac Fibroblasts. AB - Cardiac fibroblasts are commonly known as supporting cells of the cardiac network and exert many essential functions that are fundamental for normal cardiac growth as well as for cardiac remodeling process during pathological conditions. This review focuses on the roles of cardiac fibroblasts in the formation and regulation of the extracellular matrix components, and in maintaining structural, biochemical and mechanical properties of the heart. Additionally, though considered as non-excitable cells, we review the functional expression in cardiac fibroblasts of a wide variety of transmembrane ion channels which activity may contribute to key regulation of cardiac physiological processes. All together, cardiac fibroblasts which actively participate to fundamental regulation of cardiac physiology and physiopathology processes may represent pertinent targets for pharmacological approaches of cardiac diseases and lead to new tracks of therapeutic strategies. J. Cell. Physiol. 232: 725-730, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27685889 TI - Transdiaphragmatic Approach to Attenuate Porto-Azygos Shunts Inserting in the Thorax. AB - OBJECTIVE: To describe the surgical technique and document the application of a transdiaphragmatic approach to attenuate porto-azygos shunts inserting in the thoracic section of the azygos vein. STUDY DESIGN: Cadaveric study and prospective case series. ANIMALS: Canine cadavers (n=6) and client-owned dogs with porto-azygos shunts inserting in the thoracic section of the azygos vein (n=9). METHODS: In the cadavers, the azygos vein was filled with aqueous latex. Landmarks were established for creating a safe transdiaphragmatic approach to the caudal intrathoracic portion of the azygos vein. In the clinical cases, porto azygos communication was diagnosed by trans-splenic portal scintigraphy. All shunts were attenuated close to their insertion site via ventral midline celiotomy and a transdiaphragmatic approach to the shunt. Perioperative complications were recorded. RESULTS: A 3-5 cm incision, 0.5-1 cm ventral and lateral to the level of the aortic hiatus, was made in the pars lumbalis part of the diaphragm. Stay sutures at both sides of the diaphragmatic incision were placed to open up the incision and a retractor was used to push the esophagus away from the aorta. Intrathoracic insertion of the shunt was confirmed intraoperative. Exposure of the shunt insertion site at the azygos vein was excellent in all clinical cases. No intraoperative or postoperative complications were encountered. CONCLUSION: If thoracic attenuation of a porto-azygos shunt is considered, a transdiaphragmatic approach exposes the insertion site for shunt attenuation. This approach is straightforward, without unnecessary abdominal organ manipulation, and since attenuates at the insertion, avoids missing additional contributing branches. PMID- 27685890 TI - Polycationic-Shelled Capsular and Tubular Nanostructures and Their Anionic-Guest Binding Properties. AB - For the development of novel nanospace with unique electrostatic character, we prepared new capsular and tubular nanostructures by the quantitative assembly of metal ions and bent bisacridinium ligands. The capsule and tube have closed spherical and open cylindrical cavities, respectively, with diameters of around 1 nm surrounded by cationic polyaromatic panels. Thanks to the facile synthetic protocol (three steps), another polycationic capsule with an elliptical nanocavity was also prepared by using an elongated ligand. In spite of the absence of pendant hydrophilic groups, the spherical polyaromatic capsule shows sufficient water solubility due to the polycationic shell. Moreover, the highly cationic cavity (12+) can selectively encapsulate anionic organic compounds in water. PMID- 27685888 TI - K-Ras Activation Induces Differential Sensitivity to Sulfur Amino Acid Limitation and Deprivation and to Oxidative and Anti-Oxidative Stress in Mouse Fibroblasts. AB - BACKGROUND: Cancer cells have an increased demand for amino acids and require transport even of non-essential amino acids to support their increased proliferation rate. Besides their major role as protein synthesis precursors, the two proteinogenic sulfur-containing amino acids, methionine and cysteine, play specific biological functions. In humans, methionine is essential for cell growth and development and may act as a precursor for cysteine synthesis. Cysteine is a precursor for the biosynthesis of glutathione, the major scavenger for reactive oxygen species. METHODOLOGY AND PRINCIPAL FINDINGS: We study the effect of K-ras oncogene activation in NIH3T3 mouse fibroblasts on transport and metabolism of cysteine and methionine. We show that cysteine limitation and deprivation cause apoptotic cell death (cytotoxic effect) in both normal and K-ras-transformed fibroblasts, due to accumulation of reactive oxygen species and a decrease in reduced glutathione. Anti-oxidants glutathione and MitoTEMPO inhibit apoptosis, but only cysteine-containing glutathione partially rescues the cell growth defect induced by limiting cysteine. Methionine limitation and deprivation has a cytostatic effect on mouse fibroblasts, unaffected by glutathione. K-ras transformed cells-but not their parental NIH3T3-are extremely sensitive to methionine limitation. This fragility correlates with decreased expression of the Slc6a15 gene-encoding the nutrient transporter SBAT1, known to exhibit a strong preference for methionine-and decreased methionine uptake. CONCLUSIONS AND SIGNIFICANCE: Overall, limitation of sulfur-containing amino acids results in a more dramatic perturbation of the oxido-reductive balance in K-ras-transformed cells compared to NIH3T3 cells. Growth defects induced by cysteine limitation in mouse fibroblasts are largely-though not exclusively-due to cysteine utilization in the synthesis of glutathione, mouse fibroblasts requiring an exogenous cysteine source for protein synthesis. Therapeutic regimens of cancer involving modulation of methionine metabolism could be more effective in cells with limited methionine transport capability. PMID- 27685892 TI - Development of an in vivo target-engagement biomarker for TRPA1 antagonists in humans. AB - AIM: To develop a non-invasive, safe and reproducible target-engagement biomarker for future TRPA1 antagonists in healthy volunteers. METHODS: Dose finding (n = 11): 3%, 10%, and 30% cinnamaldehyde (CA) and placebo (= vehicle) was topically applied on the right forearm. One-way ANOVA with post-hoc Bonferroni was used to compare between doses. Reproducibility: 10% CA doses were topically applied during one visit on both arms (n = 10) or during two visits (n = 23) separated by a washout period of 7 days. CA-induced dermal blood flow (DBF) was assessed by laser Doppler imaging (LDI) at baseline and at 10, 20, 30, 40 and 50 min post-CA. Paired t-test was used to compare between arms or visits. Concordance correlation coefficient (CCC) was calculated to assess reproducibility. Data are expressed as percent change from baseline (mean +/- 95% CI). RESULTS: All three doses increased DBF compared to vehicle at all time-points, with the maximum response at 10-20 min post-CA. Dose response was found when comparing AUC0-50min of 30% CA (51 364 +/- 8475%*min) with 10% CA (32 239 +/- 8034%*min, P = 0.03) and 3% CA (30 226 +/- 11 958%*min, P = 0.015). 10% CA was chosen as an effective and safe dose. DBF response to 10% CA was found to be reproducible between arms (AUC0-50min , CCC = 0.91) and visits (AUC0-50min , CCC = 0.83). Based on sample size calculations, this model allows a change in CA-induced DBF of 30-50% to be detected between two independent groups of maximum 10-15 subjects with 80% power. CONCLUSIONS: Evaluation of CA-induced changes in DBF offers a safe, non-invasive and reproducible target-engagement biomarker in vivo in humans to evaluate TRPA1 antagonists. PMID- 27685891 TI - Highly sensitive detection of invasive lung cancer cells by novel antibody against amino-terminal domain of laminin gamma2 chain. AB - The laminin gamma2 chain, a subunit of laminin-332 (alpha3beta3gamma2), is a molecular marker for invasive cancer cells, but its pathological roles in tumor progression remain to be clarified. It was recently found that the most N terminal, domain V (dV) of gamma2 chain has activities to bind CD44 and stimulate tumor cell migration and vascular permeability. In the present study, we prepared a mAb recognizing gamma2 dV. Immunoblotting with this antibody, for the first time, showed that proteolytic fragments containing dV in a range of 15-80 kDa were highly produced in various human cancer cell lines and lung cancer tissues. In immunohistochemistry of adenocarcinomas and squamous cell carcinomas of the lung, this antibody immunostained the cytoplasm of invasive tumor cells and adjacent stroma much more strongly than a widely used antibody recognizing the C terminal core part of the processed gamma2 chain. This suggests that the dV fragments are highly accumulated in tumor cells and stroma compared to the processed gamma2 protein. The strong tumor cell staining with the dV antibody correlated with the tumor malignancy grade. We also found that the laminin beta3 and alpha3 chains were frequently overexpressed in tumor cells and tumor stroma, respectively. The cytoplasmic dV detection was especially prominent in tumor cells infiltrating stroma, but low in the cells surrounded by basement membranes, suggesting that the active tumor-stroma interaction is critical for the aberrant gamma2 expression. The present study suggests important roles of laminin gamma2 N terminal fragments in tumor progression. PMID- 27685893 TI - Local chemokine profiling in eosinophilic esophagitis: The synthetic absorptive matrix test. PMID- 27685895 TI - Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I. AB - Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anti- cancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. Increasing insight into the genetics and molecular biology of cancer has resulted in the identification of an increasing number of potential molecular targets, for anticancer drug discovery and development. These targets can be approached through exploitation of emerging structural biology, "rational" drug design, screening of chemical libraries, or a combination of these methods. The result is the rapid discovery of new anticancer drugs. In this article we discuss the application of molecular modeling, molecular docking and virtual high-throughput screening to multi-targeted anticancer drug discovery. Efforts have been made to employ in silico methods for facilitating the search and design of selective multi-target agents. These computer aided molecular design methods have shown promising potential in facilitating drug discovery directed at selective multiple targets and is expected to contribute to intelligent lead anticancer drugs. PMID- 27685894 TI - Cortical inhibitory deficits in Huntington's disease are not influenced by gender. AB - Huntington's disease (HD) affects GABA-mediated inhibitory circuitry in the cortex. As there is evidence that sex hormones affect GABAergic function, we investigated whether gender modulates GABA-related pathophysiological changes in HD. Fifteen premanifest HD, 11 symptomatic HD and 16 healthy control participants were assessed with paired-pulse transcranial magnetic stimulation applied to the primary motor cortex. Cortical inhibition was significantly reduced in symptomatic HD, compared with premanifest HD and controls. There was reduced inhibition in females overall, but no Group-by-Sex interaction. These findings suggest that sex hormones do not exert a direct influence on the mechanisms underpinning cortical inhibitory deficits in HD. PMID- 27685896 TI - Borderline ovarian tumors" A contemporary review of clinicopathological characteristics, diagnostic methods and therapeutic options. AB - Borderline ovarian tumors (BOTs) differ from the epithelial ovarian malignancies with their excellent prognosis, curability with surgery, and being seen in relatively young ages. Thus, fertility sparing and conservative surgical approaches are currently recommended. Preoperative diagnosis of BOTs can be challenging because, clinical and ultrasonographic features might overlap with invasive carcinomas and sometimes with benign adnexal masses. Certain characteristics such as stage at diagnosis, age of the patient and histologic features are important while deciding the extensiveness and the type of surgery. Detailed evaluation of the entire abdominal cavity and sampling all suspected areas are imperative during operation. Frozen section is essential for the intraoperative diagnosis, despite the fact that the diagnostic value of frozen section is not as high as in invasive ovarian carcinomas. Routine appendectomy and/or contralateral ovarian biopsy in cases of isolated tumor with normal appearing appendix and/or contralateral ovary are not recommended. Conservative approach might improve the recurrence rate without worsening the overall survival. The exact role of laparoscopic surgery with its advantages and disadvantages in the treatment of BOTs needs to be confirmed with further studies. PMID- 27685897 TI - Current therapeutic options targeting bone metastasis in metastatic castration resistant prostate cancer. AB - Prostate cancer is a major public health problem worldwide, still remaining the most common cancer among elder males in both Europe and USA, being responsible for approximately 30,000 deaths in USA in 2014. Nowadays, after decades of basic research, novel treatment options have emerged focusing on men suffering from metastatic castration-resistant prostate cancer improving overall survival. It is also estimated that more than 90% of such patients develop bone metastasis, resulting in a significant increase in morbidity and mortality. The purpose of this review was to discuss the treatment options targeting bone metastasis in castration-resistant prostate cancer patients by examining the available literature focusing primarily in the role of zoledronic acid, denosumab and radium 223. PMID- 27685898 TI - Ganoderma Lucidum (Reishi Mushroom) and cancer. AB - Having a long historical past in traditional Chinese medicine, Ganoderma Lucidum (G. Lucidum) is a type of mushroom believed to extend life and promote health. Due to the increasing consumption pattern, it has been cultivated and marketed intensively since the 1970s. It is claimed to be effective in the prevention and treatment of many diseases, and in addition, it exerts anticancer properties. Almost all the data on the benefits of G. Lucidum are based on laboratory and preclinical studies. The few clinical studies conducted are questionable. Nevertheless, when the findings obtained from laboratory studies are considered, it turns that G. Lucidum is likely to have some benefits for cancer patients. What is important at this point is to determine the components that will provide these benefits, and use them in drug development, after testing their reliability. In conclusion, it would be the right approach to abstain from using and incentivizing this product, until its benefits and harms are set out clearly, by considering its potential side effects. PMID- 27685899 TI - Trastuzumab 1-year vs 9-week in early-stage HER2-positive, lymph node negative breast cancer patients. AB - PURPOSE: Optimal duration of adjuvant trastuzumab therapy in early-stage HER2 positive, lymph node-negative breast cancer is unknown. To establish this, we compared 1-year and 9-week trastuzumab regimens in HER2-positive, lymph node negative early-stage breast cancer patients. METHODS: We retrospectively analyzed 4374 breast cancer patients. There were 181 early-stage, lymph node-negative breast cancer patients who were treated with adjuvant trastuzumab for either 9 week or 1-year schedule. A total of 101 patients received trastuzumab for 9 weeks and the remaining 80 patients received this adjuvant therapy for 1 year. Disease free survival (DFS) and overall survival (OS) rates of both groups were calculated. RESULTS: There was no difference between groups according to OS. Five year OS rates were 95.5% in the 9-week group and 93.3% in the 1-year group (p=0.78). DFS was affected by age, having tamoxifen therapy and disease stage. Nine-week trastuzumab group was superior to 1-year group and 5-year DFS rates were 91% in 9-week group and 81.2% in 1-year group (p=0.02). However, the 1-year group had more stage II patients than the 9-week group. We did not find any difference between groups regarding developing congestive heart failure. CONCLUSION: It appeared that 9-week trastuzumab treatment was not inferior to 1 year trastuzumab treatment in early-stage, lymph node-negative breast cancer patients. PMID- 27685901 TI - The role and the potential regulatory pathways of high expression of forkhead box C1 in promoting tumor growth and metastasis of basal-like breast cancer. AB - PURPOSE: To investigate the role of high forkhead box C1 (FOXC1) expression in basal-like breast cancer (BLBC) in vitro and vivo and the underlying regulatory mechanism. METHODS: The lentivirus vector with green fluorescent protein (GFP) was used. MDA-MB-231 cells expressing consistently high levels of FOXC1 (FOXC1 MDA-MB-231) were established. The parental MDA-MB-231 cells served as controls. Western blot analysis was used to determine the FOXC1 expression. The invasion capability was tested using the Trans-well assay. The tumorigenicity and the pulmonary metastatic ability were determined in mice in vivo. Histopathology and microarray processing and analysis were performed, and the various pathways involved and the related genes were analyzed. RESULTS: The invasion ability of FOXC1-MDA-MB-231 cells was enhanced significantly (p<0.01). Pulmonary metastases were observed in vivo in 3 of 5 mice administered FOXC1-MDA-MB-231 cells through tail vein injection. However, no pulmonary metastatic lesions were observed with MDA-MB-231 cells. The average tumor volume was larger in the mice injected with FOXC1-MDA-MB-231 than in the control mice (p<0.05). The expression of Ki-67 in the FOXC1-MDA-MB-231 injected mice was higher than in the control mice. Ten of the most gene-enriched pathways and the critical genes (IL-6 and SNAI2) were found to be related to BLBC. CONCLUSION: Elevated expression of FOXC1 enhanced the invasion ability of BLCB cells in vitro and promoted tumor growth and metastatic ability in vivo. This function may be regulated by many gene-enriched pathways and some critical genes. PMID- 27685900 TI - Clinical characteristics and management of a Greek female patient cohort with breast ductal carcinoma in situ. AB - PURPOSE: The purpose of this retrospective single-centre study was to examine the histopathological characteristics of breast ductal carcinoma in situ (DCIS) lesions in a cohort of Greek female patients and describe our experience regarding the clinical management of the disease. METHODS: The medical records from 1995 up to mid-2014 were scanned in order to trace DCIS cases. One hundred and seventy two patients (6.8% of all breast cancer cases) were diagnosed with pure DCIS and no invasive components; 32.0% underwent a second surgery, mainly due to first surgery positive margins. RESULTS: Age at first surgery ranged from 27 to 79 years (mean+/-SD 50+/-11) and median tumor size was 10mm (interquartile range/IQR7equals;12mm). Comedo necrosis (CN) was identified in 28.5% of the cases. The detection of CN was significantly associated with older age at diagnosis, larger tumor size and lower probability of highly differentiated tumors. Radiotherapy (RT) and hormonotherapy (HT) were applied to 44.8% and 63.4% of the patients, respectively. CONCLUSIONS: We implemented international practices (surgery, radiotherapy and prophylactic hormonal therapy) to patients diagnosed with DCIS and have observed only two relapses. It is our belief that DCIS requires a multidisciplinary approach and patient-tailored therapy which can potentially contribute to minimization of the local recurrence risk. PMID- 27685902 TI - Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience. AB - PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis. PMID- 27685903 TI - Acceptable adverse outcomes after delayed breast reconstruction using abdominal advancement flap - a 15-year experience. AB - PURPOSE: To evaluate the adverse outcomes after delayed breast reconstruction (DBR) by abdominal advancement flap (AAF) and permanent prosthesis in patients treated with mastectomy due to unilateral breast carcinoma, as well as to determine which factors are predictive for their occurrence. METHODS: The study included 155 patients operated at the Institute for Oncology and Radiology of Serbia from 1996 to 2010. All patients had total mastectomy and axillary lymph node dissection, followed by specific oncological treatment. Patients were selected for DBR after complete diagnostic evaluation. Adverse events were evaluated in regard to patient, disease and prostheses-related factors. RESULTS: During follow-up, DBR adverse events were observed in 23.237percnt; of the patients - the majority (91.67%) had only one. The most frequent was capsule contracture (47.22%), followed by asymmetry (22.22%), infection (16.67%) and prosthesis rupture (16.67%). There were isolated cases of prosthesis prolapse and local disease recurrence. Infections were treated conservatively in all but one patient. Other events were managed by additional operation. Statistical analysis showed that complications occurred significantly more often in patients ?51 years (vs 18-40, vs 41-50), disease stage IIb (vs Ia), T2 (vs T1) tumors and adjuvant radiotherapy (vs without). Prostheses-related factors were not significant for DBR complications, neither body mass index (BMI), nor smoking habits. CONCLUSIONS: DBR using AAF and permanent prosthesis is a safe technique with acceptable complication rate. It provides one-time surgery with satisfactory aesthetic results and good postoperative recovery. Most frequent complication is capsule contracture. Patients' age and irradiation of the chest wall after mastectomy are predictive factors for complications. PMID- 27685904 TI - The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: a retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG). AB - PURPOSE: To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. METHODS: A total of 121 previously untreated female patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. RESULTS: In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8+/ 3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values <6.08 fL, in group B values ranged from 6.09 to 8.46 fL, group C included values from 8.47 to 10.05 fL, and group D included patients with MPV values >10.06 fL. MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. CONCLUSION: We concluded that MPV can be used to predict the development of isolated bone metastases. PMID- 27685905 TI - Left laterality is an independent prognostic factor for metastasis in N3 stage breast cancer. AB - PURPOSE: Development of metastasis in patients with breast cancer (BC) is the most important negative prognostic factor and this process mainly begins with lymphatic involvement. Therefore, axillary, subclavicular, internal mammary or supraclavicular nodal involvement is a crucial step before metastasis. Anatomical differences between the right and left lymphatic drainages of the breasts may significantly affect the rate, site and time to development of distant metastasis. The purpose of this study was to investigate if laterality is an independent prognostic factor for metastasis in N3 breast cancer patients. METHODS: From a total of 4215 BC patients diagnosed between 1994 and 2015 in our center, 305 non-metastatic women with pathological N3 (pN3) nodal status at presentation were enrolled in this study. Patients were divided into two groups: left and right BC. Analysis of overall survival (OS) and time to first metastasis (TTM) was performed according to Kaplan-Meier method with log-rank test. RESULTS: The median number of lymph node involvement and lymph node ratio (number of positive lymph nodes / total number of excised lymph nodes) between the two groups was equal (14 and 0,66 respectively). Recurrence was observed in 123 patients [53 (35%) right vs 70 (44%) left group]. Patients with left BC had significantly higher rate of axial bone metastases compared with the right BC group (55.7 vs 35.8%, p<0.02, respectively). TTM was significantly shorter in the left BC group [49.1 months (95% CI 36.5-61.8) vs 103.6 months (95% CI 47.0-160); p7equals;0.03, respectively]. Median OS did not differ between the groups, however, there was a trend towards lower OS in patients with left BC (p=0.68). CONCLUSION: Left laterality in patients with pN3 non-metastatic BC is an independent prognostic factor associated with shorter TTM, increased risk of distant metastases and axial bone involvement compared with right laterality. PMID- 27685906 TI - The value of calprotectin S100A8/A9 complex as a biomarker in colorectal cancer: A systematic review. AB - PURPOSE: Associations between inflammation and carcinogenesis have been reported for many years, as originally postulated by Virchow in his studies, but the results from prospective cohort studies remain controversial. We evaluated the role of calprotectin as a biomarker for colorectal cancer (CRC). METHODS: The MEDLINE/PubMed database was thoroughly searched using the keywords: "inflammation", "colorectal cancer, "calprotectin", "carcinogenesis" and/or "biomarkers". We focused on human and animal (rodent) studies of CRC and the role of calprotectin as a new biomarker and its potential value to the diagnosis, follow-up and CRC prognosis. RESULTS: According to the literature, calprotectin seems to be a reliable sensitive marker in the diagnosis and postoperative evaluation of CRC patients at the cost of low specificity and no correlation with the progress and stage of disease. CONCLUSIONS: Calprotectin stands for a novel but well-evaluated biomarker in CRC. The experimental studies focus on the CRC microenvironment and suggest that malignant cells and tissues overexpress S100A8 and S100A9 and the heterodimer S100A8/A9. PMID- 27685907 TI - Cbl-b regulates the sensitivity of cetuximab through ubiquitin-proteasome system in human gastric cancer cells. AB - PURPOSE: Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and is approved for clinical use in combination with chemotherapy in patients affected by colorectal cancer (CRC), non small cell lung cancer (NSCLC), and head and neck cancer. Compared with these cancers, gastric cancer is relatively resistant to cetuximab and its regulatory mechanism is still unclear. METHODS: In this study, we assessed whether the ubiquitin- proteasome pathway is involved in regulating cetuximab-induced cells apoptosis in MGC803 and BGC823 gastric cancer cell lines. RESULTS: The casitas B lineage lymphoma-b (Cbl-b), a kind of E3 ubiquitin ligase, was involved in this process. Specific silenced Cbl b expression increased the expression of EGFR. CONCLUSIONS: Our findings lead to a better understanding of the mechanism of cetuximab action, and suggests that Cbl-b increases the sensitivity of cetuximab in gastric cancer cells. PMID- 27685908 TI - Prognostic indicators following curative pancreatoduodenectomy for pancreatic carcinoma: A retrospective multivariate analysis of a single centre experience. AB - PURPOSE: Survival after curative resection of pancreatic, ampullary and lower common bile duct cancer remains very poor. The aim of this study was to assess important prognostic factors in patients with resectable pancreatic cancer. METHODS: From 2006 to 2010, 156 patients underwent pancreatoduodenectomy (PD) for malignancies of pancreatic, ampullary or lower common bile duct in our institution. Based on the inclusion criteria 101 patients were selected in our retrospective statistical analysis. Of these 101 cases of malignancies, 65.4% were located in the pancreatic head, 18.8% in the ampulla and 15.8% in the lower bile duct. 48.5% of patients underwent classical PD, and 51.5% pylorus-preserving pancreatoduodenectomy (PPPD). Clinical and pathological data were collected, Kaplan-Meier method and Cox proportional hazard models were used to evaluate prognostic factors. RESULTS: Multivariate analysis revealed that blood transfusion, vascular invasion, T4 vs T1 stage, and R0 resection margins were significant negative predictors of survival. Conversely, ampullary (vs pancreatic ductal) and adjuvant chemotherapy were significantly associated with longer survival. Lymph node ratio (LNR), in all its forms, was not found to have a significant effect on survival. For all patients, tumor grading (p=0.042), resection margins (p=0.004), T stage (p=0.001), perineural invasion (p=0.029), vascular invasion (p=0.007) and age >65 years (p=0.009) were factors that impacted survival. CONCLUSION: Surgical resection margins, tumor grade, T stage, perineural invasion, vascular invasion, age >65 and adjuvant chemotherapy are the strongest predictors of survival after surgical resection of pancreatic, ampullary and lower common bile duct cancer. In this series, lymph node ratio did not impact survival. PMID- 27685910 TI - Bakuchiol inhibits cell proliferation and induces apoptosis and cell cycle arrest in SGC-7901 human gastric cancer cells. AB - PURPOSE: The main purpose of the present study was to evaluate the antiproliferative activity of bakuchiol in human gastric tumor cell line (SGC 7901) along with an effort to demonstrate its mode of action. METHODS: he effect of the compound on cell viability was evaluated by MTT assay. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution. RESULTS: The results revealed that bakuchiol exerted potent, dose-dependent as well as time-dependent growth inhibitory effects in SGC-7901 cell proliferation with IC50 values of 58.4, 42.3 and 32.5 MUM at 12, 24 and 48 hrs time intervals, respectively. On treatment with 10, 50 and 100 MUM dose of bakuchiol for 48 hrs, phase contrast microscope revealed that the cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 MUM of bakuchiol, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Bakuchiol also induced sub G1 cell cycle arrest in a dose-dependent manner. CONCLUSION: The current findings reveal that bakuchiol is a potent cytotoxic agent against gastric cancer cells and its cytotoxicity is mediated through induction of apoptosis and sub-G1 cell cycle arrest. PMID- 27685909 TI - Selective cytotoxic effect of Rhododendron luteum extract on human colon and liver cancer cells. AB - PURPOSE: The genus Rhododendron is distributed entirely in the world with the exception of South and Central America and Africa, growing in a large diversity of climatic conditions. This genus is a rich source of phenolic compounds, especially flavonoids, essential oils, chromones, terpenoids, and steroids. It has many biological properties such as antioxidant, anti-inflammatory, antiviral, antibacterial, anticancer, antidiabetic, immunomodulatory, cardioprotective and hepatoprotective among others due to their polyphenolic constituents. The objective of the current study was to evaluate the antioxidant properties and cytotoxic activity of dimethyl sulfoxide extract of flowers of Rhododendron luteum (DEFR) for the first time. METHODS: The total polyphenolic contents (TPC), total flavonoid contents (TFC) and ferric reducing antioxidant power (FRAP) of the extract were evaluated using spectrophotometric procedures. The cytotoxic activity of the extract on three cancers (human breast, colon and liver carcinoma) and human foreskin fibroblast cells was determined using the MTT assay. RESULTS: TPC and FRAP values were found 54.2+/-0.38 mg gallic acid equivalents and 164.2+/-1.77 mg trolox equivalents per to g sample, respectively. R.luteum extract exhibited selective cytotoxicity against colon and liver cancer cells compared to normal fibroblast cells, while this selective cytotoxicity was not observed in breast cancer cells. CONCLUSION: Our results demonstrate that the Rhododendron luteum may be a great source of antioxidant and antitumor natural agents due to their capability of decreasing cancer cells proliferation. PMID- 27685911 TI - Serum leptin levels may have diagnostic and predictive roles in patients with pancreatic adenocarcinoma treated with gemcitabine-based chemotherapy. AB - PURPOSE: Leptin is a highly pleiotropic adipokine. Pancreatic adenocarcinoma (PA) and leptin relationship is important. Our aim was to investigate the serum levels of leptin in patients with PA, the relationship of leptin with tumor progression and known prognostic parameters and its diagnostic, predictive and prognostic role. METHODS: Thirty-three patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum leptin levels were determined using enzyme-linked immunosorbent assay (ELISA). Age, sex, and body mass index (BMI) matched to 20 healthy controls were included in the analysis. RESULTS: The median patient age at diagnosis was 59 years (range 32-84) and 20 (61%) patients were men. The tumor was located in the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (N=19; 83%). The median follow-up time was 26.0 weeks (range 1.0-184.0). At the end of the observation period, 32 patients (97%) had died. The baseline serum leptin levels were significantly higher in patients with PA than in the control group (p=0.02). Thirty-nine percent of 23 metastatic patients who received palliative gemcitabine-based chemotherapy (gCTx) were gCTx responsive. Serum leptin levels were significantly higher in the gCTx unresponsive patients compared with gCTx -responsive (median 5.32 vs 1.16 ng/mL, p=0.004). Conversely, serum leptin concentration was found to have no prognostic role on survival (p=0.20). CONCLUSION: Serum leptin levels may be a good diagnostic and predictive tool on the response to gCTx in PA patients. PMID- 27685912 TI - Laparoscopic versus open total gastrectomy for advanced proximal gastric carcinoma: a matched pair analysis. AB - PURPOSE: Laparoscopic total gastrectomy for advanced proximal gastric carcinoma is a complex and challenging procedure, limited to a few expert centers. This study analyzed the short- and long-term outcomes of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared with open gastrectomy. METHODS: From January 2008 to January 2015, 61 patients underwent laparoscopic total gastrectomy for advanced proximal gastric carcinoma. They were matched and compared to 61 patients who underwent a conventional open operation. Short-term operative and postoperative outcomes as well as long-term outcomes, including overall survival and disease-free survival rates, were assessed. RESULTS: Patients were well matched for several preoperative factors. Overall postoperative 30-day complication rates were significantly higher for the open group. No significant difference was seen in 5-year overall survival and 5-year disease-free survival between the open and laparoscopic groups. The same result was seen in subgroup analyses of TNM stage. CONCLUSION: This study shows the feasibility of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared to open resection in regard to both short- and long-term outcomes. Laparoscopic surgery offers many advantages commonly attributed to laparoscopy and is well suited for proximal gastric carcinoma when performed by experienced surgeons. PMID- 27685913 TI - Metronomic S-1 chemotherapy plus transcatheter arterial chemoembolization (TACE): a promising treatment of hepatocellular carcinoma refractory to TACE. AB - PURPOSE: To assess the efficacy and safety of metronomic S-1 chemotherapy combination with transcatheter arterial chemoembolization (TACE) for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) refractory to TACE. METHODS: Twenty six patients met the eligibility criteria and were enrolled. TACE was performed on day 1, and metronomic S-1 chemotherapy on days 2-15. Tumor assessment was performed one month later. The primary endpoints were time to progression (TTP) and adverse events (AE). RESULTS: Twenty six patients in total received 176 TACE interventions. There were 101 TACE interventions in 15 patients of metronomic S-1 chemotherapy plus TACE (TS) and 75 in 11 patients of TACE monotherapy (TM). Fifteen TS patients received a total of 55 cycles of treatment with S-1, with a median of 4 cycles (range 2-6). The total dose of S-1 was 6165 mg per day in 15 patients (average 120 mg, range 100-125). Median TTP and overall survival (OS) of TS group were 6 months (95% CI, 4.7-7.3) and 17 months (95% CI, 15.6-18.4), respectively, while for the TM group were 4 months (95% CI, 2.4-5.6) and 15 months (95% CI, 9.2-20.8), respectively. Though there were higher tumor response rate (RR) and disease control rates (DCRs) in patients with TS, no significant differences were detected. Both treatment approaches were tolerable with low grade AE. CONCLUSIONS: In the present study, metronomic S-1 chemotherapy plus TACE in the present study was tolerable and associated with a better but not statistically significant TTP, RR and OS. It showed that metronomic S-1 chemotherapy plus TACE may be a promising treatment of BCLC Stage B HCC refractory to TACE. PMID- 27685914 TI - Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study. AB - PURPOSE: Hepatocellular carcinoma (HCC) is the one of the most common cancers and the third leading cause of cancer related mortality in the world. Unacceptable side effect and development of treatment resistance are the major concerns with the conventional chemotherapeutic agents. Combination therapy using phytotherapeutic agents is attracting the attention of investigators in view of the current needs. METHODS: In the present study we have evaluated the synergistic effect of silibinin, a nontoxic phytotherapeutic agent in combination with doxorubicin, in advanced HCC using HEPG2 cells and an orthotopic rat model of HCC. RESULTS: The results showed that silibinin strongly synergized with doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis of HEPG2 cells. Silibinin-doxorubicin combination also inhibited cdc2/p34 kinase activity when histone H1 was used as substrate. The combination regimen also moderately increased the expression of cdc25C-cyclin B1-cdc2/p34 associated upstream kinases (Chk1). Simultaneous treatment with silibinin-doxorubicin combination showed a 41% increase in the apoptotic cell death (p=0.01), which was 3-fold higher than what was observed with silibinin or doxorubicin individually. In the orthotopic rat model treatment with silibinin-doxorubicin reduced tumor growth by close to 30% at nearly twice lower dose of individual drugs in the combination group. CONCLUSIONS: Our study suggests that combination therapy using silibinin doxorubicin may show a better therapeutic efficacy in patients with HCC. These findings need to be further validated in human clinical trials. PMID- 27685915 TI - The pretreatment albumin to globulin ratio, a validated biomarker, predicts prognosis in hepatocellular carcinoma. AB - PURPOSE: Although the albumin to globulin ratio (AGR) has been proven to be a prognostic factor in several cancers, no studies have assessed its prognostic significance in hepatocellular carcinoma (HCC). Therefore, this study aimed to investigate the prognostic value of the pretreatment AGR in the survival in HCC patients. METHODS: 150 patients were enrolled, who were confirmed of HCC from October 2008 to December 2012 in Nanfang Hospital of Southern Medical University. Demographic, clinical and laboratory data were obtained. Univariate and multivariate Cox regression analysis were used to investigate the association of clinicopathological parameters with HCC patients' survival. RESULTS: Patients were divided into 2 groups: AGR?1.18 and AGR ?1.18. Patients in the high AGR (?1.18) group had longer overall survival (OS) than those in the low AGR (<1.18) group (60.16 vs 20.48 months, p<0.001). Univariate analysis showed that portal vein tumor thrombosis, grade of differentiation, extrahepatic metastasis, BCLC stage, AFP level and AGR at diagnosis were significantly associated with OS. Multivariate analysis revealed that AGR (p<0.001) and grade of differentiation (p=0.007) were independent prognostic factors for survival of HCC patients. In subgroup analysis based on age and Child-Pugh class, AGR remained a significant prognostic parameter. CONCLUSION: Low pretreatment AGR was significantly associated with shorter OS in HCC patients. The pretreatment AGR could be a useful and effective prognostic index for identifying patients with poor prognosis, even when patients have well-preserved liver reserve function. PMID- 27685918 TI - Resveratrol in lung cancer- a systematic review. AB - PURPOSE: Resveratrol, a phytochemical known for its anti- oxidative properties has been explored worldwide for anticancer potential. We performed this systematic review and meta-analysis in order to register the efficacy of resveratrol against lung carcinogenesis. METHODS: We searched PubMed for preclinical studies reporting efficacy of resveratrol alone or in combination with drugs like curcumin, cisplatin etc. against lung carcinogenesis. RESULTS: The primary outcome of eligible studies included change in overall tumor incidence as well as tumor size. In all of the above studies involving either animal models or in vitro cancer cell experiments a statistically significant reduction in tumor incidence emerged as compared with the control groups, yielding a relative risk reduction of 0.64 (p=0.002). This meta- analysis confirmed the potential of resveratrol against lung carcinogenesis. CONCLUSION: It can be concluded that resveratrol holds a good potential for future use as a highly efficient therapeutic agent to deal with deadly lung carcinogenesis. PMID- 27685916 TI - Thymidylate synthase polymorphism in Mexican patients with colon cancer treated with 5-fluorouracil. AB - PURPOSE: We analyzed the genotype and allele frequency of variable number tandem repeats (VNTR)-thymidylate synthase (TS) and its relationship with the disease evolution in colon cancer patients. METHODS: We selected 24 paraffin-embedded colon cancer tissue samples from Mexican patients who received a 5-fluorouracil (5-FU)-based chemotherapy regimen. Tumor tissue was digested with proteinase K and genomic DNA was isolated by the standard method with phenol-chloroform extraction. Polymerase chain reaction (PCR) was performed for TS genotyping of VNTR and the results were evaluated directly in a stained agarose gel. RESULTS: The allele frequency of 2 repeats (2R) was greater (0.66) than 3R (0.34) in metastatic colon cancer (x2=10.24; p=0.001)) however, no difference in allelic distribution between 2R (0.54) and 3R (0.46) in non metastatic patients was observed (x2=0.640; p=0.424). CONCLUSION: Our results suggest that Mexican patients with colon cancer present differences in the allelic distribution, the 2R allele being the most frequent. PMID- 27685919 TI - Assessment of 64-slice spiral computed tomography with perfusion weighted imaging in the early diagnosis of ground-glass opacity lung cancer. AB - PURPOSE: To evaluate the use of the 64-slice spiral computed tomography (CT) with perfusion-weighted imaging in the early diagnosis of ground-glass opacity lung cancers. METHODS: 412 patients with ground-glass opacities found by conventional CT scan in our hospital, and deemed highly suspected of being lung cancers, were enrolled in the study between February of 2012 and February of 2015. Sixty four slice spiral CTs with perfusion-weighted imaging were carried out on all patients, and the latest nodular contrast analysis software, MPR2D, 3D reconstruction technology, MIP technology and perfusion scanning technology were used to analyze lesion types, density, blood supply, peripheral signals, doubling time and tissue perfusion characteristics. This was repeated after one month, and the final pathologic diagnosis was used as a reference. RESULTS: There were 350 (84.95%) patients who were ultimately diagnosed with lung cancer. The main lesion type of lung cancer was quasi-circular, the average CT density was 56.7+/-5.4 HU, bronchial arterial enhancement increased in the nodule, peripheral signals were mainly irregular burrs, and the average doubling time was 1.2+/-0.3 s. Comparing these parameters with the ones in the non-cancer group, the differences found were with statistical significance (p<0.05). Importantly, tissue perfusion parameters of blood flow, blood volume, mean transit time and permeability surface in the lung cancer group were all significantly higher than those in non cancer group (p<0.05). CONCLUSION: From the findings in our study, we propose that 64-slice spiral CT with perfusion-weighted imaging can be used to diagnose ground-glass opacity lung cancer early, by taking into account variables such as lesion type, density, blood supply, peripheral signals, doubling time and tissue perfusion characteristics. PMID- 27685917 TI - Circulating and tissue galectin-1 and galectin-3 in colorectal carcinoma: association with clinicopathological parameters, serum CEA, IL-17 and IL23. AB - PURPOSE: Galectins are modulators of many processes critical for tumor progression and metastasis but their clinical significance is still unclear. The objective of this study was to analyze the clinical significance of Galectin-1 and Galectin-3 in the tissue and sera of patients with colorectal carcinoma (CRC). Examined were also their association with serum CEA, IL-17 and IL-23 in CRC patients. METHODS: One hundred and twenty patients with CRC were included in this study. The expression of Galectin-1 and Galectin-3 in biopsy samples of CRC was determined using immunohistochemistry (N=120). The concentrations of Galectin 1, Galectin-3, IL-17 and IL-23 in the sera of CRC patients (N=38) were determined by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: Serum Galectin-1 concentrations positively correlated with parameters of malignancy including perineural invasion (p=0.016), lymph node involvement and distant metastases (p=0.029). Higher expression of peritumoral Galectin-1 was associated with both presence of perineural invasion and poor differentiation of CRC. Serum CEA levels positively correlated with circulating Galectin-1, but inversely correlated with peritumoral Galectin-1 expression. There was no correlation between Galectin-3 and clinicopathological parameters of CRC, but it was found that Galectin-3 expression in the tumor tissue positively correlated with serum IL-17 and IL-23. Circulating Galectin-3 levels significantly correlated with IL-17 (p=0.042), but not with IL-23 in the sera of CRC patients. CONCLUSIONS: This study suggests that Galectin-1 and Galectin-3 exhibit protumorigenic activity in CRC by affecting different aspects of tumor progression. Galectin-1 facilitates tumor invasion and metastasis while Galectin-3 preferentially modulates tumor-associated inflammatory processes. PMID- 27685920 TI - Survival and prognostic factors in patients with brain metastasis: Single center experience. AB - PURPOSE: The purpose of this study was to evaluate the clinical status, prognostic factors and treatment modalities affecting survival in patients with brain metastasis. We aimed to evaluate the whole brain radiation therapy (WBRT) outcomes of patients with brain metastasis in our center. METHODS: Clinical data of 315 patients referred to our center between 2004 and 2014 with metastatic brain cancers were collected and analysed for possible relationships between survival time, age, gender, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), primary tumor, number of brain lesions, surgery, radiation therapy scheme, extracranial metastatic status and primary disease control status. RESULTS: The average patient age of onset was 58 years. The primary tumor site was lung (68%), breast (12%), melanoma (4%), colorectal (1.6%), sarcoma (1.3%) and unknown primary disease (4.4%). The rest of the patients had other primary sites. Eighty four (26.6%) patients had single brain metastasis, 71 (22.5%) had 2 or 3 lesions, and 159 (50.4%) patients had more than 3 lesions. Leptomeningeal involvement was seen in combination of paranchymal involvement in 11 (3.5%) patients. Fifty patients had undergone surgical resection. WBRT was delivered to all of the patients. Median overall survival was 6.7 months (95% CI, 5.80-7.74). Median overall survival of patients treated with combination of surgery and WBRT was significantly better compared with those treated with WBRT alone (13.5 vs 5.5 months, p=0.0001). One- and 2- year survival was 17 and 4.7%, respectively. CONCLUSIONS: The present study concludes that brain metastasis is common in cancer patients. The best overall survival was obtained by surgery+NBRT in good-condition patients. Treatment should be tailored on an individual basis to all these patients. PMID- 27685921 TI - Expression profiling of RE1-silencing transcription factor (REST), REST corepressor 1 (RCOR1), and Synapsin 1 (SYN1) genes in human gliomas. AB - PURPOSE: The repressor element 1 (RE-1) silencing transcription factor (REST) is a transcription factor which represses the expression of neuronal differentiation related genes including SYN1 gene. CoREST, encoded by RCOR1 gene, binds to the REST protein for remodeling of chromatin structure. Although there is a relation among REST, RCOR1, and SYN1 genes, the role of these genes in glioma tumors is still unclear. In this study, expressions of REST, RCOR1, and SYN1 genes were detected in primary cultures derived from tumor samples of diffuse astrocytoma (DA), anaplastic oligodendroglioma (AO), and glioblastoma multiforme (GBM) cases. METHODS: Expression profiles were analysed by RT-qPCR and the copy number variations were examined with qPCR in primary cultures. ChIP assay was performed to show binding characteristics of REST and CoREST proteins on promoter region of SYN1 gene. RESULTS: Means of relative expression for REST were as follows: 0.7898, 0.7606, and 0.7318 in DA, AO, and GBM groups, respectively. For RCOR1, expression means in DA, AO, and GBM groups were 0.7203, 0.7334, and 0.7230, respectively. SYN1 expression means were as follows: 0.3936, 0.3192, and 0.3197 in DA, AO, and GBM groups, respectively. Neither gain nor loss of copy numbers were detected for REST and RCOR1 genes in all groups. Copy loss for SYN1 was detected in primary culture of a DA case. REST and CoREST presented positive precipitation pattern on promoter region of SYN1 gene. CONCLUSIONS: Expressions of REST and RCOR1 genes may downregulate SYN1 expression in gliomas. Low expression pattern of SYN1 may maintain cancer stem-like phenotype which contributes to development of gliomas. PMID- 27685923 TI - Weekly cisplatin with radiotherapy for locally advanced head and neck squamous cell carcinoma. AB - PURPOSE: Although commonly used for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) concomitant radio-chemotherapy (RT-CT) with weekly cisplatin has not been definitely studied. We conducted a single centre retrospective study with the aim to evaluate efficacy and acute toxicity of definitive concomitant RT-CT with 40 mg/m2 weekly cisplatin in patients with locally advanced HNSCC with a particular emphasis on RT modality (conventional or accelerated) and dose of cisplatin delivered. METHODS: One hundred and twelve consecutive patients were included. They were given cisplatin 40 mg/m2)week concomitantly with conventionally fractionated (CFRT) (N=33) or accelerated (ART) (N=79) RT. RESULTS: RT was delivered according to the treatment plan in 104 patients and full dose was given to 107 patients. A median cumulative cisplatin dose of 240 mg/m2 was administered to patients treated with CFRT and of 200 mg/m2 to those treated with ART. Overall complete response rate was 81.3%. With a median follow up of 38.4 months, median overall survival (OS) was 75 months, not influenced by RT type or cisplatin dose received. The most clinically significant grade 3 or 4 acute toxicities were stomatitis (35.7%), neutropenia (25%), anemia (12.5%) and acute kidney injury (5.4%). CONCLUSIONS: Our study shows that a median cumulative dose of 200 mg/m2 cisplatin can be safely administered using a weekly regimen to patients treated with concomitant RT (CFRT or ART). Efficacy results and toxicity compare favorably with those described with triweekly cisplatin RT-CT, suggesting that a randomized comparison should be undertaken. PMID- 27685922 TI - Expression of CDCP1 and ADAM12 in the ovarian cancer microenvironment. AB - PURPOSE: The tumor microenvironment in ovarian cancer (OC) seems to play an important role, and besides tumor cells, biomarkers can derive from endothelial cells. We investigated CDCP1 and ADAM12 expression in relation with other clinical and pathological characteristics in OC patients. METHODS: We retrospectively evaluated patient files between 2006-2011. A histochemical score was developed to evaluate tumor staining, the microvessel density (MVD), and stromal expression patterns for both ADAM12 and CDCP1. A CD34 antibody was used to assess tumor MVD. RESULTS: 102 patients were selected and 83% had FIGO stage III/IV. A high CDCP1 tumor score correlated significantly with a shorter overall survival (OS) (p<0.01). Cases with positive CDCP1 had an elevated CD34 MVD (p<0.01). An absent/low ADAM12 tumor score correlated with significantly improved OS (p<0.01). Mean CD34 MVD was higher in cases with positive ADAM12 MVD (p=0.012). CONCLUSIONS: Our results indicate that both tumor markers are negative prognostic factors for overall survival and additional studies are required to validate their future potential. PMID- 27685925 TI - Incidence, mortality, and epidemiological aspects of cancers in Iran; differences with the world data. AB - PURPOSE: No comprehensive study of cancer incidence and mortality exists in Iran. This study aimed to evaluate the incidence, mortality and epidemiological aspects of cancers in our country. METHODS: In this study, information of cancer incidence and mortality in Iran was retrieved from International Cancer Registry data and reported by numbers, crude and standardized incidence and mortality rates. Cancer incidence and mortality in Iran were mapped and compared with neighboring countries and the world. RESULTS: A total of 84,829 cancer cases occurred in Iran in 2012. Overall, 39,991 cases (47.14%) were women and 44,838 (52.85%) men with male to female ratio 1.12. There were 53,350 deaths, of which 43.55% in women and 56.44% in men. The sex ratio of mortality was 1.29. Five cancers with the highest standardized incidence rates (SIR) were breast cancer (28.1), gastric cancer (15.2), prostate cancer (12.6), colorectal cancer (11.1), and esophageal cancer (8.6). Five cancers with the highest standardized mortality rates (SMR) were gastric cancer (12.9), breast cancer (9.9), esophageal cancer (7.8), lung cancer (6.9) and colorectal cancer (6.6). CONCLUSION: Our findings revealed that the incidence of some cancers increased compared to reports in previous years. The incidence and mortality were higher in men than in women. Common cancers should be detected early using screening tests such as colonoscopy and mammography. The tests can be especially useful in old age. Additional studies should be performed to investigate the causes of cancer incidence and mortality. PMID- 27685924 TI - High incidence of thyroid cancer among patients with acromegaly. AB - PURPOSE: Several studies have suggested that patients with acromegaly have an increased risk of thyroid, colorectal, breast and prostate cancers. In this study we determined the prevalence of malignant neoplasms in patients with acromegaly. METHODS: Cancer risk was evaluated in a cohort of 110 patients (M/F 48/62, age 58.63+/-13.8 years, range 30-86) with acromegaly. Mean age at diagnosis of acromegaly was 46.37+/-13.11 years. Mean period of time since diagnosis of acromegaly was 12.26+9.6 years. RESULTS: From 110 patients, cancer was diagnosed in 26 (23.6%) patients. Thyroid cancer was the most common cancer and was diagnosed in 13 patients (11.8%); other cancers encountered were gastric cancer (N=2), endometrial cancer (N-2), and breast cancer, colon cancer, prostate cancer (N-2), myelodysplastic syndrome, renal cell carcinoma, lung cancer and pancreatic carcinoma, one case each. Age, gender, age at the time of diagnosis of acromegaly, tumor size of pituitary adenoma and duration of disease were not associated with cancer development. CONCLUSIONS: This study suggests that patients with acromegaly have an increased risk of thyroid cancer and therefore they should undergo regular screening with hormonal and ultrasound evaluation of the thyroid and FNAB when required. PMID- 27685926 TI - Attachment orientations of Greek cancer patients in palliative care. A validation study of the Experiences in Close Relationships scale (ECR-M16). AB - PURPOSE: Health-care professionals may serve as attachment figures, nevertheless little research has been made in the palliative context. The psychometric properties of the brief ECR-M16 in Greek cancer patients were explored. METHODS: The ECR-M16 was translated into Greek (G-ECR-M16), and was administered to 100 patients before starting palliative care and 7 days later to test its stability. Patients (N=35) also completed the EORTC QLQ-C30 scales. RESULTS: Cronbach's alphas for the discomfort for closeness, anxiety and avoidance scales were 0.871, 0.762, and 0.761, respectively. Test-retest reliability was very satisfactory (p< 0.0005). Factor analysis yielded three factors (58.75% of the variance). Known groups validity showed that discomfort with closeness had a statistically significant correlation with advanced disease stage (p=0.022). CONCLUSIONS: The G ECR-M16 is a valid research tool for the attachment patterns' impact in Greek cancer patients. PMID- 27685927 TI - Bone metastasis in breast cancer is treated by high-dose tamoxifen. AB - PURPOSE: Bone metastases in breast cancer are quite common, and some patients may have no other site of metastasis. An effective treatment is often endocrine agents administration (tamoxifen or antiaromatases), given mainly to postmenopausal women. Radiation treatment is also effective, although difficult to perform in cases of extensive skeletal disease. Chemotherapy does not help. The purpose of this study was to investigate the effectiveness of high-dose tamoxifen in female patients with breast cancer and bone metastasis. METHODS: 28 patients with breast cancer were treated with high-dose tamoxifen. All of them had been pretreated with hormonal therapy including low-dose tamoxifen. RESULTS: The results were extremely positive with clinical amelioration and also disappearance of osteolysis in some patients. Twenty six out of 28 patients responded to the treatment, the criteria being mainly pain reduction and body mobilization (an amelioration which lasted 8 months-4 years). CONCLUSION: Tamoxifen is efficient when readministered at high dose to breast cancer patient with bone metastasis. PMID- 27685928 TI - Association of the HOTAIR rs4759314 polymorphism with cancer risk: a meta analysis. AB - PURPOSE: To explore the association between HOTAIR rs4759314 and cancer risk. METHODS: A comprehensive online search was conducted using PubMed, EMBASE, and CNKI databases to identify relevant studies. The case-control studies related to HOTAIR rs4759314 polymorphism and cancer risk were selected according to the inclusion and exclusion criteria. The retrieval time was until November 2015. After extracting the basic data information and performing an evaluation of the quality of the literature, the meta-analysis was performed using STATA 12.0 software, by calculating the odds ratio (OD) and 95% confidence interval (95% CI), and further subgroup analysis, literature publication bias testing, and sensitivity analysis. RESULTS: The studies included a total of 5025 patients with cancer and 5657 controls. The results found no significant association between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population (G vs A, OR=1.06, 95% CI :0.87-1.30 ; GG/GA vs AA, OR=1.07, 95% CI: 0.87-1.32; GG vs GA/AA, OR=0.75, 95% CI:0.39-1.43; GA vs AA, OR=1.08, 95% CI: 0.88-1.33; GG vs AA, OR=0.76, 95% CI:0.39-1.45) (all p<0.05). However, A allelic gene was associated with lower risk of gastric cancer, while G allelic gene may act as a genetic susceptibility factor for gastric cancer in Chinese population. CONCLUSION: No significant association was noted between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population. PMID- 27685929 TI - PTEN in laryngeal carcinomas. PMID- 27685930 TI - Re-affirming the necessity of sending even minor surgical specimens for histopathology: a case of inverted papilloma of the adenoids. PMID- 27685931 TI - Place of bevacizumab in radiation-induced edema and necrosis. PMID- 27685932 TI - Composite hairy cell leukemia and chronic lymphocytic leukemia. PMID- 27685933 TI - Topoisomerase IIa expression in laryngeal and oral carcinomas: is it a reliable prognostic molecular marker? PMID- 27685934 TI - Hippocrates (ca 460-370 BC) on nasal cancer. AB - The prevalence of cancer in antiquity is rather an unknown scientific field. Nevertheless, During the 5th century BC, Hippocrates and his followers, studied thoroughly this fatal disease and proposed surgical techniques and palliative drugs to confront and treat the malignant tumors caused by the black bile (the 4 humors theory). Inside Corpus Hippocraticum, nasal cancer was mentioned, alongside with its treatment. Local surgical excision, cautherization, drugs to relief the pain and face possible metastases combined with a possible pessary technique and endotracheal intubation, have been employed by the physicians of the era. PMID- 27685935 TI - Oocyte cryopreservation for fertility preservation in women with cancer. AB - PURPOSE OF REVIEW: It is necessary to clarify the fertility preservation-related points of concern that often frighten patients or physicians when it comes to deciding about oocyte cryopreservation for fertility preservation, which are often perceived as procedure limitations, are sometimes real and often theoretical and may make the prognosis worse. RECENT FINDINGS: Letrozole added to gonadotrophins for controlled ovarian stimulation is safe when applied to hormone sensitive cancer patients as it avoids associated high estradiol levels. This benefit is only for estrogens, but not for progesterone. Triggering ovulation with gonadotropin releasing hormone agonist bolus and adding the gonadotropin releasing hormone antagonist after oocyte retrieval help minimize its effect. A random start is currently widespread as neither results nor offspring are compromised, and it avoids waiting for menstruation and, therefore, delaying treatment. SUMMARY: The cumulative live birth rate is conditioned by the number of available oocytes and patient's age. Assisted reproductive technologies may help cancer patients to achieve pregnancy with good obstetric outcomes and apparent oncological safety. Although counseling should be provided on an individual basis, fertility preservation in cancer patients and later pregnancy in survivors after adequate treatment and follow-up should not be discouraged. PMID- 27685937 TI - Chemokine CXCL13 expression was up-regulated in Clostridium difficile infection. AB - Clostridium difficile infection (CDI) is the leading cause of antibiotic- and healthcare-associated diarrhea. CXCL13 is a well-known CXC chemokine involved in inflammation, but its role in CDI remains unknown. In this study, serum and fecal samplings were collected from 51 CDI patients, 50 diarrhea patients without CDI and 50 healthy control subjects to determine the CXCL13 levels by enzyme-linked immunosorbent assay (ELISA). Besides, a mouse model of C. difficile infection was established, and murine serum and colon tissues were collected for detection of CXCL13 expression using quantitative real-time RT-PCR, ELISA, Western blot, or immunohistochemistry. We found that CXCL13 concentration in serum and fecal samples from CDI patients was significantly higher compared with that from diarrhea patients without CDI and that from healthy controls. Elevated serum CXCL13 positively and significantly correlated with blood markers of inflammation and yielded an increased area under the ROC curve of 0.929. In murine C. difficile infection, CXCL13 were also dramatically increased in serum and infected colon tissues at the transcriptional and protein levels. The elevated CXCL13 levels positively and significantly correlated with inflammatory scores. Therefore, CDI is associated with enhanced release of CXCL13. This study indicated that CXCL13 may be pathogenically involved in CDI and served as a potential new biomarker for diagnosis and prognosis in CDI. PMID- 27685936 TI - Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism. AB - Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID- 27685939 TI - Incorrect Affiliations and Updated Supplement. PMID- 27685938 TI - A multi-service practice research network study of large group psychoeducational cognitive behavioural therapy. AB - BACKGROUND: This was a multi-service evaluation of the clinical and organisational effectiveness of large group psychoeducational CBT delivered within a stepped care model. METHOD: Clinical outcomes for 4451 participants in 163 psychoeducational groups delivered across 5 services were analysed by calculating pre-post treatment anxiety (GAD-7) effect sizes (Cohen's d). Overall and between-service effects were compared to published efficacy benchmarks. Multilevel modelling was used to examine if variability in clinical outcomes was explained by differences in service, group and patient-level (case-mix) variables. RESULTS: The pooled GAD-7 (pre-post) effect size for all services was d = 0.70, which was consistent with efficacy benchmarks for guided self-help interventions (d = 0.69). One service had significantly smaller effects (d = 0.48), which was explained by differences in group treatment length and case-mix. Variability between groups (i.e., group effects) explained up to 3.6% of variance in treatment outcomes. CONCLUSIONS: Large group psychoeducational CBT is clinically effective, organisationally efficient and consistent with a stepped care approach to service design. Clinical outcome differences between services were explained by group and patient variables. PMID- 27685940 TI - E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue. AB - Here, we show that E2-EPF ubiquitin carrier protein (UCP) elongated E3 independent polyubiquitin chains on the lysine residues of von Hippel-Lindau protein (pVHL) and its own lysine residues both in vitro and in vivo. The initiation of the ubiquitin reaction depended on not only Lys11 linkage but also the Lys6, Lys48 and Lys63 residues of ubiquitin, which were involved in polyubiquitin chain formation on UCP itself. UCP self-association occurred through the UBC domain, which also contributed to the interaction with pVHL. The polyubiquitin chains appeared on the N-terminus of UCP in vivo, which indicated that the N-terminus of UCP contains target lysines for polyubiquitination. The Lys76 residue of UCP was the most critical site for auto-ubiquitination, whereas the polyubiquitin chain formation on pVHL occurred on all three of its lysines (Lys159, Lys171 and Lys196). A UCP mutant in which Cys118 was changed to alanine (UCPC118A) did not form a polyubiquitin chain but did strongly accumulate mono- and di-ubiquitin via auto-ubiquitination. Polyubiquitin chain formation required the coordination of Cys95 and Cys118 between two interacting molecules. The mechanism of the polyubiquitin chain reaction of UCP may involve the transfer of ubiquitin from Cys95 to Cys118 by trans-thiolation, with polyubiquitin chains forming at Cys118 by reversible thioester bonding. The polyubiquitin chains are then moved to the lysine residues of the substrate by irreversible isopeptide bonding. During the elongation of the ubiquitin chain, an active Cys118 residue is required in both parts of UCP, namely, the catalytic enzyme and the substrate. In conclusion, UCP possesses not only E2 ubiquitin conjugating enzyme activity but also E3 ubiquitin ligase activity, and Cys118 is critical for polyubiquitin chain formation. PMID- 27685941 TI - Vitamin D Status and Predictors of Hypovitaminosis D in Internationally Adopted Children. AB - OBJECTIVES: To evaluate vitamin D status in internationally adopted children at first medical evaluation in Italy and to identify possible risk factors for hypovitaminosis D in this population. METHODS: 25-hydroxyvitamin D [25(OH)D] levels were analyzed in internationally adopted children consecutively recruited at one Italian Center between 2010 and 2014 as part of the first screening protocol. Demographic, clinical and laboratory data were prospectively collected. Serum 25(OH)D levels <10 ng/mL, <20 ng/mL, and <30 ng/mL were used to define severe vitamin D deficiency, vitamin D deficiency and hypovitaminosis D, respectively. RESULTS: 962 internationally adopted children (median age: 5.47 years; IQR:3.14-7.93) were included in the study. Median 25(OH)D level was 22.0 ng/mL (IQR:15.0-30.0 ng/mL); 710/962 (73.8%) children showed hypovitaminosis D (<30 ng/mL), 388/962 (40.3%) had vitamin D deficiency (<20 ng/dL), and 92/962 (9.6%) had severe vitamin D deficiency (<10ng/mL). No case of clinical rickets was observed. Hypovitaminosis D was particularly frequent (>90%) in children adopted from Ethiopia, Peru, India, Bulgaria and Lithuania. At multivariate analysis an increased risk of hypovitaminosis D was found to be associated with: age >= 6 years, time spent in Italy >= 3 months, blood sample taken in winter, spring or fall, compared to summer. Gender, ethnicity/continent of origin, tubercular infection, intestinal parassitosis and BMI-z-score < -2 were not associated with vitamin D status. CONCLUSION: Hypovitaminosis D is common in internationally adopted children, from all ethnic group. The evaluation of serum 25(OH)D level could be useful early after the adoption to promptly start vitamin D supplementation/treatment if needed. PMID- 27685943 TI - Maternal Antenatal Bereavement and Neural Tube Defect in Live-Born Offspring: A Cohort Study. AB - BACKGROUND: Maternal emotional stress during pregnancy has previously been associated with congenital neural malformations, but most studies are based on data collected retrospectively. The objective of our study was to investigate associations between antenatal maternal bereavement due to death of a close relative and neural tube defects (NTDs) in the offspring. METHODS: We performed a register-based cohort study including all live-born children (N = 1,734,190) from 1978-2008. Exposure was bereavement due to loss of a close relative from one year before conception to the end of the first trimester of pregnancy. The outcome was NTDs in the offspring according to the International Classification of Disease. We used multivariate logistic regression to estimate prevalence odds ratios (ORs). RESULTS: A total of 2% children were born to mothers who lost a close relative prenatally. During 30 years of follow-up, 1,115 children were diagnosed with any NTDs: spina bifida (n = 889), anencephaly (n = 85) and encephalocele (n = 164). And 23 children were diagnosed with two types of NTDs. Overall, when comparing bereaved mothers to non-bereaved mothers, no significant increased prevalence of NTDs in the offspring was seen (OR = 0.84; 95% confidence interval: 0.52-1.33). CONCLUSION: Overall maternal bereavement in the antenatal period was not related to NTDs in liveborn offspring. PMID- 27685942 TI - Obesity Impact Evaluated from Fat Percentage in Bone Mineral Density of Male Adolescents. AB - OBJECTIVE: To analyze bone mineral density (BMD) values in adolescents and to assess obesity impact, measured through body fat #x2013;on this variable through the assessment by DEXA. METHODOLOGY: A total of 318 males adolescents (12-17 years) were evaluated considering weight, height, body mass index (BMI), bone mineral density (BMD), fat and lean mass. BMD was assessed for the arms, legs, hips, and lumbar regions, as well as for total amount. Stratification of the nutritional status was determined by body fat (%BF) percentage; comparison of groups was scrutinized by analysis of variance; and the association of variables was performed using Pearson's test. RESULTS: There was a progressive increase in weight, height, and BMD for all evaluated age groups following the advance of chronological age. A negative correlation was found between the %BF with BMD in all evaluated segments. Significant differences were found between the eutrophic group compared to the overweight group and the obesity group in the evaluated segments (P <0.01) noting a reduction of up to 12.92% for the lumbar region between eutrophic and obese. CONCLUSION: The results suggest that increase %BF is associated with lower BMD among male adolescents. PMID- 27685944 TI - Racial and Gender Disparities in Incidence of Lung and Bronchus Cancer in the United States: A Longitudinal Analysis. AB - BACKGROUND: Certain population groups in the United States carry a disproportionate burden of cancer. This work models and analyzes the dynamics of lung and bronchus cancer age-adjusted incidence rates by race (White and Black), gender (male and female), and prevalence of daily smoking in 38 U.S. states, the District of Columbia, and across eight U.S. geographic regions from 1999 to 2012. METHODS: Data, obtained from the U.S. Cancer Statistics Section of the Centers for Disease Control and Prevention, reflect approximately 77% of the U.S. population and constitute a representative sample for making inferences about incidence rates in lung and bronchus cancer (henceforth lung cancer). A longitudinal linear mixed-effects model was used to study lung cancer incidence rates and to estimate incidence rate as a function of time, race, gender, and prevalence of daily smoking. RESULTS: Between 1999 and 2012, age-adjusted incidence rates in lung cancer have decreased in all states and regions. However, racial and gender disparities remain. Whites continue to have lower age-adjusted incidence rates for this cancer than Blacks in all states and in five of the eight U.S. geographic regions. Disparities in incidence rates between Black and White men are significantly larger than those between Black and White women, with Black men having the highest incidence rate of all subgroups. Assuming that lung cancer incidence rates remain within reasonable range, the model predicts that the gender gap in the incidence rate for Whites would disappear by mid-2018, and for Blacks by 2026. However, the racial gap in lung cancer incidence rates among Black and White males will remain. Among all geographic regions, the Mid-South has the highest overall lung cancer incidence rate and the highest incidence rate for Whites, while the Midwest has the highest incidence rate for Blacks. Between 1999 and 2012, there was a downward trend in the prevalence of daily smokers in both genders. However, males have significantly higher rates of cigarette smoking than females at all time points. The highest and lowest prevalence of daily smoking are found in the Mid-South and New England, respectively. There was a significant correlation between lung cancer incidence rates and smoking prevalence in all geographic regions, indicating a strong influence of cigarette smoking on regional lung cancer incidence rates. CONCLUSION: Although age adjusted incidence rates in lung cancer have decreased throughout the U.S., racial and gender disparities remain. This longitudinal model can help health professionals and policy makers make predictions of age-adjusted incidence rates for lung cancer in the U.S. in the next five to ten years. PMID- 27685945 TI - Loss of Sodium/Hydrogen Exchanger NHA2 Exacerbates Obesity- and Aging-Induced Glucose Intolerance in Mice. AB - We previously demonstrated that the sodium/hydrogen exchanger NHA2, also known as NHEDC2 or SLC9B2, is critical for insulin secretion by beta-cells. To gain more insights into the role of NHA2 on systemic glucose homeostasis, we studied the impact of loss of NHA2 during the physiological aging process and in the setting of diet-induced obesity. While glucose tolerance was normal at 2 months of age, NHA2 KO mice displayed a significant glucose intolerance at 5 and 12 months of age, respectively. An obesogenic high fat diet further exacerbated the glucose intolerance of NHA2 KO mice. Insulin levels remained similar in NHA2 KO and WT mice during aging and high fat diet, but fasting insulin/glucose ratios were significantly lower in NHA2 KO mice. Peripheral insulin sensitivity, measured by insulin tolerance tests and hyperinsulinemic euglycemic clamps, was unaffected by loss of NHA2 during aging and high fat diet. High fat diet diminished insulin secretion capacity in both WT and NHA2 KO islets and reduced expression of NHA2 in WT islets. In contrast, aging was characterized by a gradual increase of NHA2 expression in islets, paralleled by an increasing difference in insulin secretion between WT and NHA2 KO islets. In summary, our results demonstrate that loss of the sodium/hydrogen exchanger NHA2 exacerbates obesity- and aging-induced glucose intolerance in mice. Furthermore, our data reveal a close link between NHA2 expression and insulin secretion capacity in islets. PMID- 27685946 TI - Calcific Aortic Valve Disease Is Associated with Layer-Specific Alterations in Collagen Architecture. AB - Disorganization of the valve extracellular matrix (ECM) is a hallmark of calcific aortic valve disease (CAVD). However, while microarchitectural features of the ECM can strongly influence the biological and mechanical behavior of tissues, little is known about the ECM microarchitecture in CAVD. In this work, we apply advanced imaging techniques to quantify spatially heterogeneous changes in collagen microarchitecture in CAVD. Human aortic valves were obtained from individuals between 50 and 75 years old with no evidence of valvular disease (healthy) and individuals who underwent valve replacement surgery due to severe stenosis (diseased). Second Harmonic Generation microscopy and subsequent image quantification revealed layer-specific changes in fiber characteristics in healthy and diseased valves. Specifically, the majority of collagen fiber changes in CAVD were found to occur in the spongiosa, where collagen fiber number increased by over 2-fold, and fiber width and density also significantly increased. Relatively few fibrillar changes occurred in the fibrosa in CAVD, where fibers became significantly shorter, but did not otherwise change in terms of number, width, density, or alignment. Immunohistochemical staining for lysyl oxidase showed localized increased expression in the diseased fibrosa. These findings reveal a more complex picture of valvular collagen enrichment and arrangement in CAVD than has previously been described using traditional analysis methods. Changes in fiber architecture may play a role in regulating the pathobiological events and mechanical properties of valves during CAVD. Additionally, characterization of the ECM microarchitecture can inform the design of fibrous scaffolds for heart valve tissue engineering. PMID- 27685947 TI - Baboon envelope pseudotyped lentiviral vectors efficiently transduce human B cells and allow active factor IX B cell secretion in vivo in NOD/SCIDgammac-/- mice. AB - : Essentials B cells are attractive targets for gene therapy and particularly interesting for immunotherapy. A baboon envelope pseudotyped lentiviral vector (BaEV-LV) was tested for B-cell transduction. BaEV-LVs transduced mature and plasma human B cells with very high efficacy. BaEV-LVs allowed secretion of functional factor IX from B cells at therapeutic levels in vivo. SUMMARY: Background B cells are attractive targets for gene therapy for diseases associated with B-cell dysfunction and particularly interesting for immunotherapy. Moreover, B cells are potent protein-secreting cells and can be tolerogenic antigen-presenting cells. Objective Evaluation of human B cells for secretion of clotting factors such as factor IX (FIX) as a possible treatment for hemophilia. Methods We tested here for the first time our newly developed baboon envelope (BaEV) pseudotyped lentiviral vectors (LVs) for human (h) B-cell transduction following their adaptive transfer into an NOD/SCIDgammac-/- (NSG) mouse. Results Upon B-cell receptor stimulation, BaEV-LVs transduced up to 80% of hB cells, whereas vesicular stomatitis virus G protein VSV-G-LV only reached 5%. Remarkably, BaEVTR-LVs permitted efficient transduction of 20% of resting naive and 40% of resting memory B cells. Importantly, BaEV-LVs reached up to 100% transduction of human plasmocytes ex vivo. Adoptive transfer of BaEV-LV transduced mature B cells into NOD/SCID/gammac-/- (NSG) [non-obese diabetic (NOD), severe combined immuno-deficiency (SCID)] mice allowed differentiation into plasmablasts and plasma B cells, confirming a sustained high-level gene marking in vivo. As proof of principle, we assessed BaEV-LV for transfer of human factor IX (hFIX) into B cells. BaEV-LVs encoding FIX efficiently transduced hB cells and their transfer into NSG mice demonstrated for the first time secretion of functional hFIX from hB cells at therapeutic levels in vivo. Conclusions The BaEV-LVs might represent a valuable tool for therapeutic protein secretion from autologous B cells in vivo in the treatment of hemophilia and other acquired or inherited diseases. PMID- 27685949 TI - Corneal keratocyte transition to mesenchymal stem cell phenotype and reversal using serum-free medium supplemented with fibroblast growth factor-2, transforming growth factor-beta3 and retinoic acid. AB - Keratocytes of the corneal limbal stroma can derive populations of mesenchymal stem cells (MSC) when expanded in vitro. However, once a corneal MSC (cMSC) phenotype is achieved, regaining the keratocyte phenotype can be challenging, and there is no standardised differentiation medium. Here, we investigated the transition of keratocytes to cMSC and compared different supplements in their ability to return cMSC to a keratocyte phenotype. Immunofluorescence and quantitative reverse transcription polymerase chain reaction demonstrated in vivo keratocyte expression of aldehyde dehydrogenase 3A1, CD34 and keratocan, but not any of the typical MSC markers (CD73, CD90, CD105). As the keratocytes were expanded in vitro, the phenotypic profile reversed and the cells expressed MSC markers but not keratocyte markers. Differentiating the cMSC back to a keratocyte phenotype using nonsupplemented, serum-free medium restored keratocyte markers but did not maintain cell viability or support corneal extracellular matrix production. Supplementing the differentiation medium with combinations of fibroblast growth factor-2, transforming growth factor-beta3 and retinoic acid maintained viability, restored expression of CD34, aldehyde dehydrogenase 3A1 and keratocan, and facilitated production of abundant extracellular matrix as shown by immunofluorescent staining for collagen-I and lumican, alongside quantitative assays for collagen and glycosaminoglycan production. However, no differentiation medium was able to downregulate the expression of MSC markers in the 21-day culture period. This study shows that the keratocyte to MSC transition can be partially reversed using serum-free media and supplementation with retinoic acid, fibroblast growth factor-2 and transforming growth factor-beta3 and can enhance this effect. This is relevant for development of corneal regenerative strategies that require the production of a keratocyte phenotype. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27685948 TI - Replicate and randomize, or lie. AB - Biological populations are naturally variable. Investigators need to replicate observations to estimate their characteristics. They must also randomize selection to estimate those characteristics without bias and with known confidence. Both replication and randomization are necessary. PMID- 27685950 TI - Comparison of Epidermal Growth Factor Receptor Mutations between Metastatic Lymph Node Diagnosed by EBUS-TBNA and Primary Tumor in Non-Small Cell Lung Cancer. AB - INTRODUCTION: Although the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasing for epidermal growth factor receptor (EGFR) testing in lung cancer, the discordance rate in EGFR mutations between lymph node (LN) samples obtained by EBUS-TBNA and primary tumor (PT) is not well known. Thus, we compared the EGFR mutation status of LN samples obtained by EBUS TBNA and PTs to estimate the efficacy of using EBUS-TBNA specimens for EGFR testing in advanced, non-squamous, non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Using data of patients from the EBUS-TBNA database (N = 1914) obtained between January 2009 and January 2013, we identified 100 treatment naive, advanced, non-squamous NSCLC patients (stage 3 and 4) with matched LN specimens obtained by EBUS-TBNA and PT specimens. Of these, 74 patients with paired specimens were feasible for EGFR mutation analysis, which we performed using a direct sequencing method. RESULTS: Of the 74 cases, at least one major [exon 19 deleted (19del) and L858R] or minor (T790M, exon 20 insertion, and other point mutations) EGFR mutation was detected in 31 cases (41.9%), which included PT (n = 31, 41.9%) and LN (n = 28, 37.8%) specimens. Major mutations were detected in 25 PT (33.8%, 19del = 13, L858R = 12) and 22 LN (29.8%, 19del = 11, L858R = 11) specimens. The discordance rate in major mutations between matched PT and LN specimens was 4.1% (3/74). Among minor mutations, T790M was detected in LN specimen only in 2 cases with L858R in PT and LN. The discordance rate major and minor EGFR mutations combined between matched PT and LN specimens was 12% (9/74). CONCLUSIONS: We observed a high concordance rate of major EGFR mutations between matched LN specimens sampled by EBUS-TBNA and PTs, suggesting that LN samples obtained by EBUS-TBNA from advanced non-squamous NSCLC patients are effective for use in EGFR mutation testing. PMID- 27685951 TI - The effectiveness of nurse education and training for clinical alarm response and management: a systematic review. AB - AIMS AND OBJECTIVES: To identify the effectiveness of education interventions provided for nurses for clinical alarm response and management. BACKGROUND: Some education has been undertaken to improve clinical alarm response, but the evidence for evaluating effectiveness for nurse education interventions is limited. DESIGN: Systematic review. METHODS: A systematic review of experimental studies published in English from 2005-2015 was conducted in four computerised databases (MEDLINE, EMBASE, CINAHL and Scopus). After identification, screening and appraisal using Joanna Briggs Institute instruments, quality research papers were selected, data extraction and analysis followed. RESULTS: Five studies met the inclusion criteria for alarm response and no articles were concerned with clinical alarm education for management. All had different types and methods of interventions and statistical pooling was not possible. Response accuracy, response time and perceptions were consistent when different interventions were adopted. A positive effect was identified when learning about general alarms, single alarms, sequential alarms and medium-level alarms for learning as the primary task. Nurses who were musically trained had a faster and more accurate alarm response. Simulation interventions had a positive effect, but the effect of education provided in the care unit was greater. Overall, clinical alarm awareness was improved through education activities. CONCLUSIONS: Nurses are the main users of healthcare alarms and work in complex environments with high numbers of alarms, including nuisance alarms and other factors. Alarm-related adverse events are common. The findings of a small number of experimental studies with diverse evidence included consideration of various factors when formulating education strategies. The factors which influence effectiveness of nurse education are nurse demographics, nurse participants with musical training, workload and characteristics of alarms. Education interventions based in clinical practice settings increase education effectiveness, although simulation can be effective. No study shows any type of intervention results in sustained improvement. RELEVANCE TO CLINICAL PRACTICE: There are workload implications in education and the matching of load, number and type of alarms with nurse demographics which should be evaluated. There also needs to be a connection between education and the clinical setting to contribute to clinical alarm awareness for undergraduate nurses and practicing nurses. Education solely supported by employers is insufficient. Patient safety and long-term effects must be further explored. PMID- 27685952 TI - A population-based analysis of mortality in patients with Turner syndrome and hypoplastic left heart syndrome using the Texas Birth Defects Registry. AB - BACKGROUND: Hypoplastic left heart syndrome (HLHS) is strongly associated with Turner syndrome (TS); outcome data when these conditions coexist is sparse. We aimed to investigate long-term survival and causes of death in this population. METHODS: The Texas Birth Defects Registry was queried for all live born infants with HLHS during 1999-2007. We used Kaplan-Meier and Cox regression analyses to compare survival among patients with HLHS with TS (HLHS/TS+) to patients who had HLHS without genetic disorders or extracardiac birth defects (HLHS/TS-). RESULTS: Of the 542 patients with HLHS, 11 had TS (2.0%), 71 had other extracardiac birth defects or genetic disorders, and 463 had neither. The median follow-up time was 4.2 y (interquartile range [IQR] 2.1-6.5). Comparing those with HLHS/TS+ to HLHS/TS-, 100% versus 35% were female (P < .001), and median birth weight was 2140 g (IQR 1809-2650) versus 3196 g (IQR 2807-3540, P < .001). Neonatal mortality was 36% in HLHS/TS+ versus 27% in HLHS/TS- (log rank = 0.431). Ten of the 11 TS+ patients died during the study period for cumulative mortality of 91% versus 50% (hazard ratio (HR) for TS+: 2.90, 95% CI 1.53-5.48). Six patients died prior to surgery, 5 underwent Stage 1 palliation (S1P), 3 died after S1P, 2 survived past S2P, and one of these died at age 19 mo. The underlying cause of death was listed as congenital heart disease on all the death certificates of HLHS/TS+ patients. In multivariable analysis controlling for low birth weight (<2500 g), TS remained associated with significantly increased cumulative mortality, although females without TS had higher mortality than males (HR for TS+ versus males: 2.42, 95% CI 1.24-4.73; HR for TS- females versus males: 1.41, 95% CI 1.08-1.83). CONCLUSION: TS with HLHS is associated with significant mortality. The increased mortality in females without documented TS calls to question if TS is undetected in a portion of females with HLHS. PMID- 27685953 TI - Exhaustive Training Leads to Hepatic Fat Accumulation. AB - Recently, we demonstrated that an overtraining (OT) protocol for mice based on downhill running sessions increased the hepatic phosphorylation of 70-kDa ribosomal protein S6 kinase 1 (S6K1; Thr389), a downstream target of the mammalian target of rapamycin complex 1 (mTORC1). In liver, the overactivation of the Akt/mTORC1 pathway induces lipogenesis via regulation of the action of sterol regulatory element binding protein-1 (SREBP-1) at multiple steps. Herein, we verified the effects of three running OT models with same external load (i.e., the product between intensity and volume of training), but performed in downhill, uphill and without inclination, on the proteins related to the mTORC1 signaling pathway, the protein content of the SREBP-1, ACC, and FAS, and the morphological characteristics of C57BL/6 mouse livers. In summary, the downhill running-induced OT model up-regulated the levels of major proteins of the mTORC1 signaling pathway, the protein levels of SREBP-1 (p125 precursor) and induced signs of cell swelling accompanied by acute inflammation. The other two OT protocols performed uphill and without inclination did not modulate the most analyzed molecular proteins, but induced hepatic morphological alterations, suggesting an acute pathological adaptation. The three OT models induced hepatic fat accumulation. J. Cell. Physiol. 232: 2094-2103, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27685954 TI - Laparoscopic Evaluation of Umbilical Disorders in Calves. AB - OBJECTIVE: To describe a laparoscopic technique for evaluating umbilical disorders in calves, including feasibility, visualization of umbilical structures, and related complications. STUDY DESIGN: Prospective clinical study. ANIMALS: Male calves (15 Holstein, 2 Montbeliard) with umbilical disorders (n=17). METHODS: Calves <2 months old with obvious umbilical disease were assessed by clinical examination and ultrasonography of the umbilical structures. Laparoscopic evaluation was performed in dorsal recumbency under subarachnoid lumbosacral anesthesia and sedation. An open insertion technique with short 60 mm cannulas was used after creating 2 portals 10 cm cranial to the umbilicus (one 5 cm left of midline for the laparoscope and one 5 cm right of midline as an instrument portal). After laparoscopy, abnormal tissues were resected by laparotomy during the same anesthetic period. RESULTS: Laparoscopic evaluation of umbilical structures was performed quickly (mean surgery time 7.1 +/- 2.5 minutes). Umbilical structures could be completely visualized in all calves without intraoperative complications. In addition to abnormalities previously detected on ultrasound, laparoscopy enabled detection of adhesions 7 calves that were not suspected on ultrasound, as well as focal enlargements of the umbilical arteries and urachus close to the bladder in 5 calves. Laparoscopy failed to detect abnormalities observed with ultrasound or laparotomy in 4 calves, including small hernias and omphalitis. CONCLUSION: Laparoscopic evaluation of umbilical structures was performed safely and quickly in young calves and allowed complete evaluation of intra-abdominal umbilical structures and may, therefore, be a useful adjunct to physical examination and ultrasound to fully assess the abdomen in calves. PMID- 27685955 TI - Variation in Soil Respiration across Soil and Vegetation Types in an Alpine Valley. AB - BACKGROUND AND AIMS: Soils of mountain regions and their associated plant communities are highly diverse over short spatial scales due to the heterogeneity of geological substrates and highly dynamic geomorphic processes. The consequences of this heterogeneity for biogeochemical transfers, however, remain poorly documented. The objective of this study was to quantify the variability of soil-surface carbon dioxide efflux, known as soil respiration (Rs), across soil and vegetation types in an Alpine valley. To this aim, we measured Rs rates during the peak and late growing season (July-October) in 48 plots located in pastoral areas of a small valley of the Swiss Alps. FINDINGS: Four herbaceous vegetation types were identified, three corresponding to different stages of primary succession (Petasition paradoxi in pioneer conditions, Seslerion in more advanced stages and Poion alpinae replacing the climactic forests), as well as one (Rumicion alpinae) corresponding to eutrophic grasslands in intensively grazed areas. Soils were developed on calcareous alluvial and colluvial fan deposits and were classified into six types including three Fluvisols grades and three Cambisols grades. Plant and soil types had a high level of co-occurrence. The strongest predictor of Rs was soil temperature, yet we detected additional explanatory power of sampling month, showing that temporal variation was not entirely reducible to variations in temperature. Vegetation and soil types were also major determinants of Rs. During the warmest month (August), Rs rates varied by over a factor three between soil and vegetation types, ranging from 2.5 MUmol m-2 s-1 in pioneer environments (Petasition on Very Young Fluvisols) to 8.5 MUmol m-2 s-1 in differentiated soils supporting nitrophilous species (Rumicion on Calcaric Cambisols). CONCLUSIONS: Overall, this study provides quantitative estimates of spatial and temporal variability in Rs in the mountain environment, and demonstrates that estimations of soil carbon efflux at the watershed scale in complex geomorphic terrain have to account for soil and vegetation heterogeneity. PMID- 27685956 TI - Management of pharmaceutical substances in the environment: Lithuanian case study. AB - Investigation on the sources, discharges and related risks for the environment of the pharmaceutical substance (PhS) diclofenac (DCF) was performed in Lithuania, a country of the Baltic Sea region, for the first time. The investigation only refers to DCF as a PhS for human use; emissions from animal husbandry were not considered. In the first stage of the research, the main sources and pathways of DCF via substance flow analysis were identified within the country. During the second stage, DCF flows along the wastewater treatment plants (WWTPs) in two different cities were measured in order to assess the current levels of pharmaceutical residues in the environment. Furthermore, environmental risk assessment was carried out by taking into account the parameters of consumption data and elimination rate in WWTPs. Then, the assessment of different technical and managerial removal approaches was accomplished in an environmental management model of wastewater containing PhS, based on the framework of environmental systems theory. PMID- 27685958 TI - Improvement of the intersection method for the quantification of filamentous organisms: basis and practice for bulking and foaming bioindication purposes. AB - Bulking and foaming phenomena in activated sludge wastewater treatment plants are in most cases related to the abundance of filamentous microorganisms. Quantifying these microorganisms should be a preliminary stage in their control. In this paper, the simplicity of quantifying them based on the intersection method is demonstrated, by redescribing the theory and applying a new improved protocol; new data of interest are also provided. The improved method allows us to use it with stained smears, including epifluorescence techniques. The error that could be made, when considering the distribution of filamentous bacteria in fresh microscope preparations in two dimensions rather than three is negligible. The effect of the different types of filamentous microorganisms on the settleability was also studied. The effect of the total extended filament length on the sludge settleability was shown to depend on the type of filamentous organism and how it aggregates. When these groups of filamentous organisms are found in small aggregations and there is an increase in the number of filamentous organisms, the sludge volume index (SVI) increases proportionally to the filament length. However, when aggregation increases, the impact on the SVI is significantly lower. PMID- 27685957 TI - Occurrence of phosphorus, iron, aluminum, silica, and calcium in a eutrophic lake during algae bloom sedimentation. AB - Phosphorus (P) in a water body is mainly controlled by the interaction between surface sediment and the overlying water column after the complete control of external pollution. Significant enhancement of P in a water body would cause eutrophication of lakes. Thus, a better understanding is needed of the occurrences of P between the sediment and water column in eutrophic lakes. Here, we measured total phosphorus (TP) and major elements (Fe, Al, Ca, Mn, Si) in the water column, and total nitrogen, organic matter, TP and major oxides (Fe2O3, Al2O3, CaO, SiO2) in surface sediment of Chaohu Lake, a continuously eutrophic lake. The results showed that the rank of TP levels was western lake > eastern lake > southern lake. There were significantly positive correlations between TP (including water TP and sedimentary TP) and Fe, Al, Mn, while the correlation coefficients between water TP and sedimentary TP were -0.43, -0.41 and 0.18 for the western, eastern and southern lake respectively. The negative and significant correlations of water TP and sedimentary TP may indicate that the risk of sedimentary P release was great in the western and eastern lake during algae bloom sedimentation, while the southern lake showed weak P exchange between the sediment and water column. PMID- 27685959 TI - Assessment of the use of red mud as a catalyst for photodegradation of bisphenol A in wastewater treatment. AB - This study aimed to investigate the use of red mud (RM) - a byproduct of aluminum production, as a photocatalyst, which was characterized physical-chemically and used in the photodegradation of the target compound bisphenol A (BPA). Chemical processing was performed in the RM (acid treatment, chemical reduction and calcination) to verify the most active catalyst. From the results obtained, a complete degradation kinetics of BPA was carried out using a synthetic matrix (BPA in deionized water) and a real matrix (BPA in wastewater) using natural RM/calcined and TiO2 for comparison. The results indicated the potential use of the RM/calcined, which was able to degrade between 88 and 100% of the pollutant in a synthetic sample. Tests on a real effluent sample resulted in degradation rates that ranged from 59 to 100% with chemical oxygen demand reductions of up to 23% using natural RM/calcined in comparison to TiO2. The blank system (irradiation of the solution without the use of a photocatalyst) and the natural RM/calcined one, resulted in reductions of the toxicity in the effluent sample (measured by EC20 using the marine bacteria Vibrio fischeri) of about 12 times, whereas the same treatment using TiO2 resulted in a toxicity reduction of only seven times. Within these results, the RM/calcined showed potential to be used in wastewater treatment in polishing processes. PMID- 27685960 TI - Prediction of coagulation and flocculation processes using ANN models and fuzzy regression. AB - Coagulation and flocculation are two main processes used to integrate colloidal particles into larger particles and are two main stages of primary water treatment. Coagulation and flocculation processes are only needed when colloidal particles are a significant part of the total suspended solid fraction. Our objective was to predict turbidity of water after the coagulation and flocculation process while other parameters such as types and concentrations of coagulants, pH, and influent turbidity of raw water were known. We used a multilayer perceptron (MLP), a radial basis function (RBF) of artificial neural networks (ANNs) and various kinds of fuzzy regression analysis to predict turbidity after the coagulation and flocculation processes. The coagulant used in the pilot plant, which was located in water treatment plant, was poly aluminum chloride. We used existing data, including the type and concentrations of coagulant, pH and influent turbidity, of the raw water because these types of data were available from the pilot plant for simulation and data was collected by the Tehran water authority. The results indicated that ANNs had more ability in simulating the coagulation and flocculation process and predicting turbidity removal with different experimental data than did the fuzzy regression analysis, and may have the ability to reduce the number of jar tests, which are time consuming and expensive. The MLP neural network proved to be the best network compared to the RBF neural network and fuzzy regression analysis in this study. The MLP neural network can predict the effluent turbidity of the coagulation and the flocculation process with a coefficient of determination (R2) of 0.96 and root mean square error of 0.0106. PMID- 27685961 TI - Evaluating photo-degradation of COD and TOC in petroleum refinery wastewater by using TiO2/ZnO photo-catalyst. AB - The aim of this study is to investigate the performance of combined solar photo catalyst of titanium oxide/zinc oxide (TiO2/ZnO) with aeration processes to treat petroleum wastewater. Central composite design with response surface methodology was used to evaluate the relationships between operating variables for TiO2 dosage, ZnO dosage, air flow, pH, and reaction time to identify the optimum operating conditions. Quadratic models for chemical oxygen demand (COD) and total organic carbon (TOC) removals prove to be significant with low probabilities (<0.0001). The obtained optimum conditions included a reaction time of 170 min, TiO2 dosage (0.5 g/L), ZnO dosage (0.54 g/L), air flow (4.3 L/min), and pH 6.8 COD and TOC removal rates of 99% and 74%, respectively. The TOC and COD removal rates correspond well with the predicted models. The maximum removal rate for TOC and COD was 99.3% and 76%, respectively at optimum operational conditions of TiO2 dosage (0.5 g/L), ZnO dosage (0.54 g/L), air flow (4.3 L/min), reaction time (170 min) and pH (6.8). The new treatment process achieved higher degradation efficiencies for TOC and COD and reduced the treatment time comparing with other related processes. PMID- 27685962 TI - Removal of phosphorus from water by using volcanic ash soil (VAS): batch and column experiments. AB - Using low-cost and naturally available materials is considered an optimal adsorbent for removing phosphorus (P) from water due to its simplicity and economic efficiency. This study examined the removal of P from water using volcanic ash soil (VAS) by batch and column experiments. The maximum adsorption capacity of P was 2.94 mg g-1, estimated from the batch experiment according to a Langmuir isotherm. The column study showed a higher adsorption capacity of 5.57 mg g-1. The breakthrough curve showed that influent water containing 2 mg L-1 P was completely purified by VAS within 1,230 pore volumes (PV). The breakthrough and saturation points of the curves were 3,100 PV and 14,875 PV, respectively. After an adsorption column was loaded with 20,508 PV, a regeneration procedure was developed to determine whether an ion exchange of P with chloride occurred or adsorbed P in the columns could be eluted. Approximately 20% of P was recovered from columns by desorption tests, regardless of NaCl solution or deionized water. Specific surface area and mineral concentrations are both important characteristics that improve the adsorption capacity of VAS. The present study suggests that VAS is a promising adsorbent to remove P in water. PMID- 27685963 TI - Adsorption of cadmium by biochar produced from pyrolysis of corn stalk in aqueous solution. AB - The purpose of this work is to investigate adsorption characteristic of corn stalk (CS) biochar for removal of cadmium ions (Cd2+) from aqueous solution. Batch adsorption experiments were carried out to evaluate the effects of pH value of solution, adsorbent particle size, adsorbent dosage, and ionic strength of solution on the adsorption of Cd2+ onto biochar that was pyrolytically produced from CS at 300 degrees C. The results showed that the initial pH value of solution played an important role in adsorption. The adsorptive amount of Cd2+ onto the biochar decreased with increasing the adsorbent dosage, adsorbent particle size, and ionic strength, while it increased with increasing the initial pH value of solution and temperature. Cd2+ was removed efficiently and quickly from aqueous solutions by the biochar with a maximum capacity of 33.94 mg/g. The adsorption process was well described by the pseudo-second-order kinetic model with the correlation coefficients greater than 0.986. The adsorption isotherm could be well fitted by the Langmuir model. The thermodynamic studies showed that the adsorption of Cd2+ onto the biochar was a spontaneous and exothermic process. The results indicate that CS biochar can be considered as an efficient adsorbent. PMID- 27685964 TI - Characterization of dissolved organic matter in the secondary effluent of pulp and paper mill wastewater before and after coagulation treatment. AB - Meeting the regulatory discharge standards for pulp and paper mill wastewater has become ever more difficult because of its recalcitrant and colored dissolved organic matter (DOM). In this study, the variation of DOM from the secondary effluent of pulp and paper mill wastewater before and after coagulation was investigated based on hydrophobicity/hydrophilicity, apparent molecular weight (MW) and fluorescence. DOM fractions of the secondary effluent were all with the apparent MW <20 kDa. Particularly, the hydrophobic acids (HOA) fraction, mainly composed of humic-like materials, was the major component, and it also had the highest color and SUVA254 (UV254 to dissolved organic carbon ratio). Hydrophilic bases (HIB) and hydrophilic neutrals (HIN) fractions were the other important parts besides HOA. Coagulation can remove all DOM fractions to different extent, and it was more effective for organic compounds with MW > 5 kDa. The removal efficiencies of humic-like, fulvic-like and soluble microbial by-product-like constituents in HOA and HIB fractions were much higher than in other fractions. Even so, the coagulation effluent still contained large amounts of contaminants with complicated fluorophores and apparent MW <5 kDa, and HOA and HIN fractions were also the major parts in the coagulation effluent. PMID- 27685965 TI - Linking nitrification characteristic and microbial community structures in integrated fixed film activated sludge reactor by high-throughput sequencing. AB - The primary goal of this study is to investigate ammonia removal, abundance of nitrifying bacteria and microbial community structures in a laboratory-scale integrated fixed film activated sludge (IFAS) reactor. The results of Illumina MiSeq sequencing based on 16S rRNA genes showed Proteobacteria and Bacteroidetes were the dominant phyla in both biofilm and suspended sludge samples in the IFAS reactor. The dominant ammonia-oxidizing bacteria (AOB) species was Nitrosomonas and the dominant nitrite-oxidizing bacteria species was Nitrospira. The contribution of biofilm to ammonia removal increased from 4.0 +/- 0.9% to 37.0 +/ 2% when the temperature decreased from 25 degrees C to 10 degrees C. The real time polymerase chain reaction (PCR) result showed the abundance of AOB in suspended sludge was higher than that in biofilm at the same time. However, nitrification is more dependent on attached growth than on suspended growth in the IFAS reactor at 15 degrees C and 10 degrees C and the abundance of AOB in biofilm was also higher than that in suspended sludge. The more robust ammonia removal rate at low temperatures by biofilm contributed to the relatively stable ammonia removal, and biofilm attached on carriers in the IFAS reactor is advantageous for nitrification in low-temperature environment. PMID- 27685967 TI - Modeling of eutrophication and strategies for improvement of water quality in reservoirs. AB - The purpose of this study is to survey the thermal regime and eutrophication states in Ilam reservoir in Iran as the case study. For this purpose and to find solutions for improving the water's quality in the reservoir, two general strategies for reducing the entering pollution loads and water depletions from the reservoir's outlets were analyzed by use of the CE-QUAL-W2 model. Results of the simulation of the present situation show the existence of thermal stratification during summer, which results in the qualitative stratification in the reservoir. According to the qualitative criteria, the Ilam reservoir's state is between mesotrophic and eutrophic. Results of the scenarios of reduction of the nutrients show that in the scenario of 50% reduction of the phosphorus and nitrogen loads into the reservoir, the state of the reservoir would recover from eutrophic to semi-eutrophic. Also, release of water from the reservoir during September, October and November would cause the restoration of the quality of water in the reservoir. To avoid the occurrence of critical eutrophication in the reservoir, reducing the ponding time in the reservoir by fast depletion, preventing entrance of the upstream villages' sewage and agricultural drained waters, which are sources of nitrate and phosphate contamination into the rivers, and also management of the usage of agricultural fertilizers have been suggested. PMID- 27685966 TI - Phthalate degradation by glow discharge plasma enhanced with pyrite in aqueous solution. AB - In order to prevent health risk from potential exposures to phthalates, a glow discharge plasma (GDP) process was applied for phthalate degradation in aqueous solution. The results revealed that the phthalate derivatives 4-hydroxyphthalic acid, 4-methylphthalic acid and 4-tert-butylphthalic anhydride could be degraded efficiently in GDP process (498 V, 0.2 A) with high removal efficiencies of over 99% in 60 minutes. Additionally, pyrite as a promising heterogeneous iron source in the Fenton reaction was found to be favorable for GDP process. The phthalate degradation reaction could be significantly enhanced by the continuous formation of *OH and the inhibition of the quenching reaction in the pyrite Fenton system due to the constant dissolution of Fe(II) from pyrite surface. Meanwhile, the initial pH value showed little impact on the degradation of phthalates and the energy efficiency of GDP system for phthalate degradation ranged between 0.280 * 10-9 and 1.210 * 10-9 mol/J, which is similar to the GDP system with phenol, bisphenol A and methyl tert-butyl ether as the substrates. Further, the X-ray diffraction and scanning electron microscopy with energy dispersive X-ray spectroscopy analyses indicated that the pyrite was relatively stable in GDP system and there was no obvious polymeric compound formed on the catalyst surface. Overall, this GDP process offers high removal efficiency, simple technology, considerable energy efficiency and the applicability to salt containing phthalate wastewater. PMID- 27685968 TI - Adsorption of reactive dye from aqueous solution and synthetic dye bath wastewater by Eucalyptus bark/magnetite composite. AB - In the present study, Eucalyptus camaldulensis bark/magnetite composite (EBMC) was used for a potential application as a low-cost adsorbent for the removal of Reactive Black 5 (RB5). The adsorption experiments were performed with aqueous solution (RB5 + distilled water) and synthetic dye bath wastewater (SDBW) in order to investigate the potential application of EBMC in the textile industry. The effects of the various parameters, the initial dye concentration, the temperature, the pH, and the EBMC dosage on the adsorption were investigated. It was found that the adsorption capacity of EBMC increases by increasing the RB5 concentration and temperature and by decreasing the dosage of EBMC. 0.8 g EBMC was found to be sufficient for the removal of 250 mg/L RB5 from 150 mL SDBW with ~85% removal efficiency. The Koble-Corrigan isotherm model described the adsorption process more effectively (R2 = 0.997) than the Langmuir, Freundlich, the Dubinin-Radushkevich and the Jovanovic isotherm models. The Langmuir isotherm predicted a 370.7 mg/g maximum adsorption capacity. The thermodynamic analysis showed that the adsorption of RB5 onto the EBMC was an endothermic process. The multiple linear regression analysis was used in order to determine the cumulative effects of independent variables on the adsorption capacity. PMID- 27685969 TI - Algicidal activity of an actinomycete strain, Streptomyces rameus, against Microcystis aeruginosa. AB - An actinomycete strain (KKU-A3) with algicidal activity against Microcystis aeruginosa was isolated from soil in Khon Kaen Province, Thailand. Based on its phenotypic characteristics and 16S rDNA sequence, strain KKU-A3 was identified as Streptomyces rameus. Strain KKU-A3 also exhibited algicidal activity against the cyanobacteria Synechococcus elongatus, Cylindrospermum sp. and Oscillatoria sp. A mathematical and statistical technique was used to optimize the culture conditions and maximize its anti-Microcystis activity. The single factor experiments indicated that glucose and casein were the most effective carbon and nitrogen sources, respectively, and produced the highest anti-Microcystis activity. Response surface methodology indicated that the optimum culture conditions were 19.81 g/L glucose and 2.0 g/L casein at an initial pH of 7.8 and an incubation temperature of 30 degrees C. The anti-Microcystis activity increased from 82% to 95% under optimum conditions. In an internal airlift loop bioreactor, the removal of M. aeruginosa KKU-13 by the bacterium was investigated in batch and continuous flow experiments. In the batch experiment, KKU-A3 displayed maximum anti-Microcystis activity of 95% at day 7, whereas in the continuous flow experiment, KKU-A3 displayed maximum anti-Microcystis activity of 95% at day 10. PMID- 27685970 TI - An approach to biodegradation of chlorobenzenes: combination of Typha angustifolia and bacterial effects on hexachlorobenzene degradation in water. AB - Although rhizoremediation is an effective approach to remove organic pollutants from the environment, little is known about the mechanism of hexachlorobenzene (HCB) biodegradation in water. In this study, we used Typha angustifolia (T. angustifolia) grown in sterile Hoagland nutrient solution to determine the rhizosphere effects on the ability of bacteria in water to reduce HCB levels. The results revealed that T. angustifolia could facilitate HCB degradation and that the initial HCB concentration was the major factor responsible for HCB degradation in nutrient solution. Furthermore, HCB biodegradation in low-HCB nutrient solution with T. angustifolia fitted the first-order kinetics, owing to the high concentration of total organic carbon, low HCB toxicity, and unique bacterial community in the T. angustifolia rhizosphere. Denaturing gradient gel electrophoresis indicated that the rhizosphere effects and different dosages of HCB have significant effects on the bacterial communities by repressing and favoring certain populations. The most successful bacteria to adapt to HCB contamination was Bacillus sp., while the dominant bacterial phyla in HCB polluted water were Proteobacteria and Firmicutes. PMID- 27685971 TI - Characterization and application of surface-molecular-imprinted-polymer modified TiO2 nanotubes for removal of perfluorinated chemicals. AB - The removal of perfluorinated chemicals (PFCs) during wastewater reclamation is a great concern. However, the existing advanced treatment processes are inefficient for the removal of PFCs from secondary effluents of municipal wastewater treatment plants (WWTPs) because other coexistent pollutants with less environmental significance are removed simultaneously. Therefore, research on high-selectivity, low-cost removal methods is needed. The S-MIP-TiO2 nanotube (NT) photocatalysts were fabricated, characterized and tested for removal of PFCs from wastewater for the first time. Scanning electron microscopy and Fourier transform infrared spectroscopy show that the TiO2 NTs (average diameter 60 nm) were successfully imprinted with functional groups (i.e. carboxyl). The adsorption selectivity and photocatalytic activity of the S-MIP-TiO2 NTs over perfluorooctanoic acid (PFOA) were improved compared with neat TiO2 NTs and interestingly, were higher at low PFOA concentrations (10 to 100 ng/L, as normal PFC concentrations in secondary effluents) than at high concentrations (10 to 1,000 mg/L). With S-MIP-TiO2 NTs used as photocatalysts, some representative PFCs were selectively and rapidly removed from secondary effluents of a municipal WWTP. S-MIP-TiO2 NTs exhibited excellent regeneration performance. Thus, photocatalytic treatment using is promising for effective removal of PFCs from secondary effluents of municipal WWTPs. PMID- 27685972 TI - A study on Cu and Ag doped ZnO nanoparticles for the photocatalytic degradation of brilliant green dye: synthesis and characterization. AB - Novel polyvinyl pyrrolidone capped pure, Ag (1-3%) and Cu doped (1-3%) zinc oxide (ZnO) nanoparticles (NPs) were successfully synthesized via the co-precipitation method. The synthesized NPs were characterized by UV-visible spectrophotometry, X ray diffraction (XRD), energy dispersive spectroscopy (EDS) and field emission scanning electron microscopy (FE-SEM). Compared to pure ZnO, the absorption bands of Ag and Cu doped ZnO NPs were shifted and, further, the band gap energy was also decreased which confirms the incorporation of Ag and Cu into the ZnO lattice. The XRD diffraction peak confirms that all the synthesized compounds are found to be of highly crystalline hexagonal wurtzite structure. In addition, the presence of Ag and Cu in the ZnO NPs was further evidenced from EDS analysis. FE SEM images established the morphology of the doped ZnO NPs which was not affected by the addition of Ag and Cu. The photocatalytic activity of undoped, Ag doped (1 3%) and Cu doped (1-3%) ZnO NPs were tested with brilliant green dye under UV irradiation. Degradation study reveals that doping has a distinct effect on the photocatalytic behavior of ZnO NPs. In addition to that, kinetic, thermodynamic and reusability studies have been performed for the 2% Ag doped ZnO NPs. PMID- 27685973 TI - Fertilizer from dried human urine added to ash and lime - a potential product from eco-sanitation system. AB - This research explored the possibility of making fertilizer at a laboratory from source separated and untreated human urine added to ash and lime by drying at low temperatures. A mixture of ash and lime (1:1) was used as drying agent and human urine was applied as undiluted and fresh. Ash and lime were chosen as drying agents for maintaining a pH > 10 during the drying process, which should inhibit urea hydrolysis in urine, and thereby urea should be retained in the drying agent. The drying technique was developed and drying capacity of the system was quantified; three specific temperatures (20 degrees , 35 degrees , 60 degrees C) and two airflow rates (1 L/min and 5 L/min) were used in the experiment. A mass balance for nitrogen in the system was obtained. It was evident from the experiment that urea can be retained by maintaining a high pH (>10). Urine drying at 20 degrees C was not a feasible option, since rate of evaporation was very low. The highest retention of inflow nitrogen at 35 degrees C and 60 degrees C were 74% and 54%, respectively, in the produced fertilizer. Reduced evaporation rate, flooding of urine over drying agent, and blockage in airflow influenced nitrogen loss and concentration of nitrogen in the final product. PMID- 27685974 TI - Which is better for optimizing the biosorption process of lead - central composite design or the Taguchi technique? AB - The aim of this study is to evaluate central composite design (CCD) and the Taguchi technique in the adsorption process. Contact time, initial concentration, and pH were selected as the variables, and the removal efficiency of Pb was chosen for the designated response. In addition, face-centered CCD and the L9 orthogonal array were used for the experimental design. The result indicated that, at optimum conditions, the removal efficiency of Pb was 80%. However, the value of R2 was greater than 0.95 for both the CCD and Taguchi techniques, which revealed that both techniques were suitable and in conformity with each other. Moreover, the results of analysis of variance and Prob > F < 0.05 showed the appropriate fit of the designated model with the experimental results. The probability of classifying the contributing variables by giving a percentage of the response quantity (Pb removal) made the Taguchi model an appropriate method for examining the effectiveness of different factors. pH was evaluated as the best input factor as it contributed 66.2% of Pb removal. The Taguchi technique was additionally confirmed by three-dimensional contour plots of CCD. Consequently, the Taguchi method with nine experimental runs and easy interaction plots is an appropriate substitute for CCD for several chemical engineering functions. PMID- 27685976 TI - Improvements in permeation and fouling resistance of PVC ultrafiltration membranes via addition of Tetronic-1107 and Triton X-100 as two non-ionic and hydrophilic surfactants. AB - Two non-ionic and hydrophilic surfactant additives, Tetronic-1107 and Triton X 100, were added to poly(vinyl chloride)/NMP polymeric solution to prepare ultrafiltration membranes via immersion precipitation. Surfactants at three different weight percentages up to 6 wt% were added, and the fabricated membranes were characterized and their performance for water treatment in the presence of bovine serum albumin (BSA) as a foulant was assessed. The scanning electron microscopy images indicated remarkable changes in morphology due to higher thermodynamic instability after surfactant addition. The membranes are more porous with more macro-voids in the sub-layer. Plus, the membranes become more hydrophilic. Water flux increases for the modified membranes by nearly two times and the ability of membranes for flux recovery increases from 66% to over 83%. BSA rejection reduces slightly with the addition of surfactants, however this parameter is still almost over 90% for the membranes with the highest amount of surfactants. PMID- 27685975 TI - Impact of multiple wastewater feedings on the efficiency of nutrient removal in an IFAS-MBSBBR: number of feedings vs. efficiency of nutrient removal. AB - This article presents the results of research into the influence of one, two and three wastewater feedings in a cycle on efficiency and performance of combined biological nitrogen and phosphorus removal in an integrated fixed-film activated sludge and moving-bed sequencing batch biofilm reactor (IFAS-MBSBBR). The experiment lasted 158 days and was conducted in two laboratory models of the IFAS MBSBBR with an active volume of 28 L. It was found that along with an increase in the number of wastewater feedings, an increase in nitrogen removal efficiency was observed (from 56.9 +/- 2.30% for a single feeding to 91.4 +/- 1.77% for three feedings). Moreover, the contribution of simultaneous nitrification/denitrification in nitrogen removal increased (from 2.58% for a single feeding to 69.5% for three feedings). Systems with a greater number of feedings stimulated the process of denitrifying phosphorus removal. Regardless of the way in which wastewater feeding was applied to the IFAS-MBSBBR, highly efficient chemical oxygen demand (COD) removal (94.8 +/- 1.80%) and biological phosphorus removal (98.9 +/- 0.87%) were achieved. PMID- 27685977 TI - Removal of copper ions from aqueous solution by the sodium salt of the maleic acid-allylpropionate-styrene terpolymer. AB - The sodium salt of the maleic acid-allylpropionate-styrene terpolymer was used for recovery of copper ions from aqueous solution. Effects of contact time, sorbent weight and initial Cu2+ ion concentrations on removal efficiency were tested. The maximum experimental sorption capacity of the sorbent for copper ions is 0.71 g g-1. The sorption isotherm of copper ions onto a prepared polymer sorbent has been studied and the equilibrium data were analyzed using Langmuir and Freundlich isotherm models. The adsorption isotherm data showed that copper ions adsorption on the sorbent was better fitted to the Langmuir isotherm model. The Lagergren pseudo-first- and pseudo-second-order kinetic models were applied to examine the kinetics of the copper ions sorption by the synthesized sorbent. The kinetic data are best described by the pseudo-second-order model. The calculated value of the maximum sorption capacity by the pseudo-second-order equation (0.62 g g-1) corresponds well with its experimentally found value (0.71 g g-1). Considering the obtained kinetic data, and the Fourier transform infrared spectroscopy (FT-IR) and UV-vis spectra of the sorbent after the sorption, it is possible to come to the conclusion that during the sorption process Cu2+ ions enter a complex with the carboxylic groups of the maleic acid units of the sorbent. PMID- 27685978 TI - Optimization of operation conditions for domestic sewage treatment using a sequencing batch biofilm filter. AB - A sequencing batch biofilm filter (SBBF) was applied to treat domestic sewage. The bioreactor consisted of fibrous filler in the upper part and ceramsite filter media in the lower part. The impacts of the most important factors including dissolved oxygen (DO), water temperature and hydraulic retention time (HRT) were evaluated on contaminants removal during the operation of the SBBF. Changes in DO (1.5-4.0 mg/L) and water temperature (2-30 degrees C) had little effect on the removal of chemical oxygen demand (COD), but had a greater impact on the removal of total nitrogen (TN) and NH4+-N. Changes in HRT (8-14 h) had little effect on the removal of COD, but had a greater impact on the removal of TN, NH4+-N and total phosphorus. The optimal operating parameters for the SBBF were as follows: DO of 2-3 mg/L, water temperature above 10 degrees C, and HRT of 10-13 h. Furthermore, a simple kinetic model was developed, reflecting the relationship between COD and HRT. PMID- 27685979 TI - Soil fertilization with wastewater biosolids - monitoring changes in the 'soil fertilizer-plant' system and phosphorus recovery options. AB - The aim of this study is to establish changes that may occur after a prolonged application of wastewater sludge treated to biosolids, in the 'soil-fertilizer plant' system. Thirteen experimental plots with different soil types planted with experimental crops were investigated in order to evaluate the suitability of these biosolids as soil conditioners and fertilizers. The biosolids were incorporated in soil starting in 2006 in different quantities (from 6 tons per ha) for various arrays. The rate of application was calculated on the basis of imported nitrogen and was consistent with the characteristics of the sludge, soil diversity, growing crop requirements, and other factors. In 2013 (after 7 years of land use) average soil samples from the same arrays were taken and analyzed. No chemical fertilizer was applied during the experimental period. The results show that the use of sewage biosolids as a soil improver in accordance with local legislation does not pose any serious environmental risks but can maintain and improve soil fertility and crop yield. A slight increase in Cu and Zn in plants was detected, however the content of heavy metals in all soil samples was below maximum allowable limits and no signs of phytotoxicity were observed. PMID- 27685980 TI - Metal-Free Hydrogen Atom Transfer from Water: Expeditious Hydrogenation of N Heterocycles Mediated by Diboronic Acid. AB - A hydrogenation of N-heterocycles mediated by diboronic acid with water as the hydrogen atom source is reported. A variety of N-heterocycles can be hydrogenated with medium to excellent yields within 10 min. Complete deuterium incorporation from stoichiometric D2 O onto substrates further exemplifies the H/D atom sources. Mechanism studies reveal that the reduction proceeds with initial 1,2 addition, in which diboronic acid synergistically activates substrates and water via a six-membered ring transition state. PMID- 27685981 TI - Effects of high latitude protected areas on bird communities under rapid climate change. AB - Anthropogenic climate change is rapidly becoming one of the main threats to biodiversity, along with other threats triggered by human-driven land-use change. Species are already responding to climate change by shifting their distributions polewards. This shift may create a spatial mismatch between dynamic species distributions and static protected areas (PAs). As protected areas represent one of the main pillars for preserving biodiversity today and in the future, it is important to assess their contribution in sheltering the biodiversity communities, they were designated to protect. A recent development to investigate climate-driven impacts on biological communities is represented by the community temperature index (CTI). CTI provides a measure of the relative temperature average of a community in a specific assemblage. CTI value will be higher for assemblages dominated by warm species compared with those dominated by cold dwelling species. We here model changes in the CTI of Finnish bird assemblages, as well as changes in species densities, within and outside of PAs during the past four decades in a large boreal landscape under rapid change. We show that CTI has markedly increased over time across Finland, with this change being similar within and outside PAs and five to seven times slower than the temperature increase. Moreover, CTI has been constantly lower within than outside of PAs, and PAs still support communities, which show colder thermal index than those outside of PAs in the 1970s and 1980s. This result can be explained by the higher relative density of northern species within PAs than outside. Overall, our results provide some, albeit inconclusive, evidence that PAs may play a role in supporting the community of northern species. Results also suggest that communities are, however, shifting rapidly, both inside and outside of PAs, highlighting the need for adjusting conservation measures before it is too late. PMID- 27685984 TI - About Professor Abraham Aaron Buschke (1868-1943) and Wilhelm Ludwig Lowenstein (1895-1959): The fate of two Jewish dermatologists during the National Socialism. PMID- 27685983 TI - Consensus Analysis of Whole Transcriptome Profiles from Two Breast Cancer Patient Cohorts Reveals Long Non-Coding RNAs Associated with Intrinsic Subtype and the Tumour Microenvironment. AB - Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes and diseases such as cancer; however, their functions remain poorly characterised. Several studies have demonstrated that lncRNAs are typically disease and tumour subtype specific, particularly in breast cancer where lncRNA expression alone is sufficient to discriminate samples based on hormone status and molecular intrinsic subtype. However, little attempt has been made to assess the reproducibility of lncRNA signatures across more than one dataset. In this work, we derive consensus lncRNA signatures indicative of breast cancer subtype based on two clinical RNA-Seq datasets: the Utah Breast Cancer Study and The Cancer Genome Atlas, through integration of differential expression and hypothesis-free clustering analyses. The most consistent signature is associated with breast cancers of the basal-like subtype, leading us to generate a putative set of six lncRNA basal-like breast cancer markers, at least two of which may have a role in cis-regulation of known poor prognosis markers. Through in silico functional characterization of individual signatures and integration of expression data from pre-clinical cancer models, we discover that discordance between signatures derived from different clinical cohorts can arise from the strong influence of non-cancerous cells in tumour samples. As a consequence, we identify nine lncRNAs putatively associated with breast cancer associated fibroblasts, or the immune response. Overall, our study establishes the confounding effects of tumour purity on lncRNA signature derivation, and generates several novel hypotheses on the role of lncRNAs in basal-like breast cancers and the tumour microenvironment. PMID- 27685982 TI - The noradrenergic locus coeruleus as a chronic pain generator. AB - Central noradrenergic centers such as the locus coeruleus (LC) are traditionally viewed as pain inhibitory; however, complex interactions among brainstem pathways and their receptors modulate both inhibition and facilitation of pain. In addition to the well-described role of descending pontospinal pathways that inhibit spinal nociceptive transmission, an emerging body of research now indicates that noradrenergic neurons in the LC and their terminals in the dorsal reticular nucleus (DRt), medial prefrontal cortex (mPFC), spinal dorsal horn, and spinal trigeminal nucleus caudalis participate in the development and maintenance of allodynia and hyperalgesia after nerve injury. With time after injury, we argue that the balance of LC function shifts from pain inhibition to pain facilitation. Thus, the pain-inhibitory actions of antidepressant drugs achieved with elevated noradrenaline concentrations in the dorsal horn may be countered or even superseded by simultaneous activation of supraspinal facilitating systems dependent on alpha1 -adrenoreceptors in the DRt and mPFC as well as alpha2 adrenoreceptors in the LC. Indeed, these opposing actions may account in part for the limited treatment efficacy of tricyclic antidepressants and noradrenaline reuptake inhibitors such as duloxetine for the treatment of chronic pain. We propose that the traditional view of the LC as a pain-inhibitory structure be modified to account for its capacity as a pain facilitator. Future studies are needed to determine the neurobiology of ascending and descending pathways and the pharmacology of receptors underlying LC-mediated pain inhibition and facilitation. (c) 2016 Wiley Periodicals, Inc. PMID- 27685985 TI - An In Silico Knockout Model for Gastrointestinal Absorption Using a Systems Pharmacology Approach - Development and Application for Ketones. AB - Gastrointestinal absorption and disposition of ketones is complex. Recent work describing the pharmacokinetics (PK) of d-beta-hydroxybutyrate (BHB) following oral ingestion of a ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) found multiple input sites, nonlinear disposition and feedback on endogenous production. In the current work, a human systems pharmacology model for gastrointestinal absorption and subsequent disposition of small molecules (monocarboxylic acids with molecular weight < 200 Da) was developed with an application to a ketone monoester. The systems model was developed by collating the information from the literature and knowledge gained from empirical population modelling of the clinical data. In silico knockout variants of this systems model were used to explore the mechanism of gastrointestinal absorption of ketones. The knockouts included active absorption across different regions in the gut and also a passive diffusion knockout, giving 10 gut knockouts in total. Exploration of knockout variants has suggested that there are at least three distinct regions in the gut that contribute to absorption of ketones. Passive diffusion predominates in the proximal gut and active processes contribute to the absorption of ketones in the distal gut. Low doses are predominantly absorbed from the proximal gut by passive diffusion whereas high doses are absorbed across all sites in the gut. This work has provided mechanistic insight into the absorption process of ketones, in the form of unique in silico knockouts that have potential for application with other therapeutics. Future studies on absorption process of ketones are suggested to substantiate findings in this study. PMID- 27685987 TI - Laparoscopic Rectal Resection-Ready for Prime Time? PMID- 27685986 TI - HIV-associated malignancies in children. AB - PURPOSE OF REVIEW: HIV-infected children are at an increased risk of developing cancer. Many of the cancers in HIV-infected children are linked to immunosuppression and oncogenic coinfections. Worldwide most HIV-infected children live in sub-Saharan Africa, but cancer data for this population are scarce. In this article, we review the current literature on the epidemiology and prevention of cancer in HIV-infected children. RECENT FINDINGS: Combined antiretroviral therapy (cART) reduces the risk of developing cancer in HIV infected children. Cancer risk remains increased in children who start cART at older ages or more advanced immunosuppression as compared with children who start cART at younger age and with mild immunosuppression. Starting cART before severe immunosuppression develops is key to prevent cancer in HIV-infected children but most children in low-income countries start cART at severe immunosuppression levels. Vaccination against high-risk variants of human papillomavirus may protect again human papillomavirus-associated cancer later in life. However, tailoring of human papillomavirus vaccination guidelines for HIV-infected children and young women awaits answers to determine the best vaccination strategies. SUMMARY: Better data on the short-term and long-term risks of developing cancer and the effects of preventive measures in HIV-infected children from regions with high burden of HIV/AIDS are urgently needed. PMID- 27685988 TI - Chronic Obstructive Pulmonary Disease Mismatch: A Case of Tracheal Hamartoma. AB - OBJECTIVE: To demonstrate the diagnostic challenge of tracheal hamartoma in a patient with chronic obstructive pulmonary disease (COPD). CLINICAL PRESENTATION AND INTERVENTION: A 65-year-old man with COPD was admitted with sudden onset of asphyxia attacks related to the position of his body. Computerized tomography (CT) of the neck showed a soft tissue mass with calcification, which occluded more than two-thirds of the proximal part of the trachea. The tumor was completely removed, and histopathology confirmed hamartoma. CONCLUSION: This case report showed the detection of a primary tracheal tumor on CT. This finding enabled the correct diagnosis and led to appropriate treatment in the form of surgery. PMID- 27685989 TI - Hemodynamics in Coronary Arterial Tree of Serial Stenoses. AB - Serial segmental narrowing frequently occurs in humans, which alters coronary hemodynamics and further affects atherosclerotic progression and plaque formation. The objective of this study was to understand the distribution of hemodynamic parameters in the epicardial left main coronary arterial (LMCA) tree with serial stenoses reconstructed from patient computer tomography angiography (CTA) images. A finite volume method was used in conjunction with the inlet pressure wave and outlet flow resistance. The time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) were determined from the flow field. A stenosis at a mother vessel mainly deteriorated the hemodynamics near the bifurcation while a stenosis at a daughter vessel affected the remote downstream bifurcation. In comparison with a single stenosis, serial stenoses increased the peak pressure gradient along the main trunk of the epicardial left anterior descending arterial tree by > 50%. An increased distance between serial stenoses further increased the peak pressure gradient. These findings have important implications on the diagnosis and treatment of serial coronary stenoses. PMID- 27685990 TI - Cocaine-and Amphetamine Regulated Transcript (CART) Peptide Is Expressed in Precursor Cells and Somatotropes of the Mouse Pituitary Gland. AB - Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1. PMID- 27685991 TI - Multiplexed Molecular Imaging of Biomarker-Targeted SERS Nanoparticles on Fresh Tissue Specimens with Channel-Compressed Spectrometry. AB - Biomarker-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have been explored as a viable option for targeting and imaging multiple cell surface protein biomarkers of cancer. While it has been demonstrated that this Raman-encoded molecular imaging (REMI) technology may potentially be used to guide tumor-resection procedures, the REMI strategy would benefit from further improvements in imaging speed. Previous implementations of REMI have utilized 1024 spectral channels (camera pixels) in a commercial spectroscopic CCD to detect the spectral signals from multiplexed SERS NPs, a strategy that enables accurate demultiplexing of the relative concentration of each NP "flavor" within a mixture. Here, we investigate the ability to significantly reduce the number of spectral-collection channels while maintaining accurate imaging and demultiplexing of up to five SERS NP flavors, a strategy that offers the potential for improved imaging speed and/or detection sensitivity in future systems. This strategy was optimized by analyzing the linearity of five multiplexed flavors of SERS NPs topically applied on tissues. The accuracy of this binning approach was then validated by staining tumor xenografts and human breast tumor specimens with a mixture of five NP flavors (four targeted NPs and one untargeted NP) and performing ratiometric imaging of specific vs. nonspecific NP accumulation. We demonstrate that with channel-compressed spectrometry using as few as 16 channels, it is possible to perform REMI with five NP flavors, with < 20% error, at low concentrations (< 10 pM) that are relevant for clinical applications. PMID- 27685992 TI - Sequence-Dependent T:G Base Pair Opening in DNA Double Helix Bound by Cren7, a Chromatin Protein Conserved among Crenarchaea. AB - T:G base pair arising from spontaneous deamination of 5mC or polymerase errors is a great challenge for DNA repair of hyperthermophilic archaea, especially Crenarchaea. Most strains in this phylum lack the protein homologues responsible for the recognition of the mismatch in the DNA repair pathways. To investigate whether Cren7, a highly conserved chromatin protein in Crenarchaea, serves a role in the repair of T:G mispairs, the crystal structures of Cren7-GTAATTGC and Cren7 GTGATCGC complexes were solved at 2.0 A and 2.1 A. In our structures, binding of Cren7 to the AT-rich DNA duplex (GTAATTGC) induces opening of T2:G15 but not T10:G7 base pair. By contrast, both T:G mispairs in the GC-rich DNA duplex (GTGATCGC) retain the classic wobble type. Structural analysis also showed DNA helical changes of GTAATTGC, especially in the steps around the open T:G base pair, as compared to GTGATCGC or the matched DNAs. Surface plasmon resonance assays revealed a 4-fold lower binding affinity of Cren7 for GTAATTGC than that for GTGATCGC, which was dominantly contributed by the decrease of association rate. These results suggested that binding of Cren7 to DNA leads to T:G mispair opening in a sequence dependent manner, and therefore propose the potential roles of Cren7 in DNA repair. PMID- 27685993 TI - Prenatal Clinical Assessment of NT-proBNP as a Diagnostic Tool for Preeclampsia, Gestational Hypertension and Gestational Diabetes Mellitus. AB - Common complications of pregnancy include preeclampsia (PE), gestational hypertension (GH) and gestational diabetes mellitus (GDM). Hypertensive disorders (PE/GH) and GDM may result in greater maternal, fetal and neonatal morbidity and mortality. Women with PE/GH, one of the most common causes of heart burden in an obstetrical setting, present with elevated serum levels of BNP and NT-proBNP. The aim of this study was to shed more light on the role of NT-proBNP in pathophysiology of PE, GH and GDM. The study included 156 pregnant women with singleton pregnancies. A total of 26 women developed arterial hypertension during pregnancy, 14 were diagnosed with PE, and GDM was detected in 81 patients. The control group included 35 women with uncomplicated pregnancies, normal arterial blood pressure and normal glucose concentrations. Patients with GH presented with significantly higher serum concentrations of NT-proBNPthan normotensive women (65.5 vs. 37.4 pg/ml; p = 0.0136). Serum levels of NT-proBNP in patients with PE were the highest of all the analyzed subsets, being significantly higher than in women without this condition (89.00 vs. 37.4pg/ml,p = 0,0136). However, women with and without GDM did not differ significantly in terms of their serum NT proBNPconcentrations. Serum NT-proBNP (pg/ml) (p = 0.0001) and BMI (p<0.0001) turned out to be independent predictors of GH on multivariate logistic regression analysis.Moreover, serum NT-proBNP (pg/ml) was identified as an independent indicator of PE (p = 0.0016). A significant inverse correlation was found between birth weight and maternal serum NT-proBNP concentrations. In our opinion, NT proBNP can be a useful clinical marker of GH and PE. Determination of NT-proBNP levels may be helpful in identification of patients with PE and GH and in their qualification for intensive treatment; this in turn, may be reflected by better neonatal outcomes. PMID- 27685994 TI - Dietary Vitamin C Intake Reduces the Risk of Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators. AB - Despite growing interest in the protective role that dietary antioxidant vitamins may have in the development of type 2 diabetes (T2D), little epidemiological evidence is available in non-Western populations especially about the possible mediators underlying in this role. The present study aimed to investigate the association of vitamin C and vitamin E intakes with T2D risk in Chinese adults and examine the potential mediators. 178 incident T2D cases among 3483 participants in the Harbin People Health Study (HPHS), and 522 newly diagnosed T2D among 7595 participants in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases (HDNNCDS) were studied. In the multivariable adjusted logistics regression model, the relative risks (RRs) were 1.00, 0.75, and 0.76 (Ptrend = 0.003) across tertiles of vitamin C intake in the HDNNCDS, and this association was validated in the HPHS with RRs of 1.00, 0.47, and 0.46 (Ptrend = 0.002). The RRs were 1.00, 0.72, and 0.76 (Ptrend = 0.039) when T2D diagnosed by haemoglobin A1c in the HDNNCDS. The mediation analysis discovered that insulin resistance (indicated by homeostasis model assessment) and oxidative stress (indicated by plasma total antioxidative capacity) partly mediated this association. But no association was evident between vitamin E intake and T2D. In conclusion, our research adds further support to the role of vitamin C intake in reducing the development of T2D in the broader population studied. The results also suggested that this association was partly mediated by inhibiting or ameliorating oxidative stress and insulin resistance. PMID- 27685996 TI - Attenuating the Negative Impact of Unemployment: The Interactive Effects of Perceived Emotional Intelligence and Well-Being on Suicide Risk. AB - A growing body of research has demonstrated that deficits in well-being may be related to increased suicide risk, but there is only a limited number of studies that have focused on specific protective factors that can serve as a buffer against suicidal ideation and behaviours. Given that unemployment may be a factor leading to increased risk for suicide, this study assessed whether perceived EI might be a potential moderator in the relationship between life satisfaction/happiness and suicidal behaviours in a relatively large sample of unemployed individuals. Participants were 1125 unemployed (506 men and 619 women) who completed satisfaction with life and happiness questionnaires, the Suicidal Behaviours Questionnaire and the Wong and Law Emotional Intelligence Test. Consistent with the interaction hypothesis, lower scores in life satisfaction and happiness were associated with higher levels of current suicidal behaviours, and perceived EI scores moderated these relationships. Interventions targeting well being via the promotion of emotional abilities may be useful in the prevention of suicidal ideation in the unemployed. The implications for these findings for research and practice are discussed. PMID- 27685997 TI - A Lipidomic Analysis of Placenta in Preeclampsia: Evidence for Lipid Storage. AB - In preeclampsia, maternal insulin resistance leads to defective expansion of adipocytes, enhanced adipocyte lipolysis, up-regulation of very low density lipoprotein synthesis, maternal hypertriglyceridaemia and the potential for ectopic fat storage. Our aim was to quantitate and compare the total amount and type of lipid in placenta from pregnancies complicated with preeclampsia and healthy pregnancies. Quantitative lipid analysis of lipid extracts from full thickness placental biopsies was carried out by shotgun lipidomics. Placental lipid profiles from pregnancies complicated by preeclampsia (n = 23) were compared to healthy pregnancies (n = 68), and placenta from intrauterine growth restriction pregnancies (n = 10) were used to control for gross differences in placental pathology. Placentae from pregnancies complicated with preeclampsia had higher neutral lipid content than healthy placentae (40% higher triacyglycerol (P = 0.001) and 33% higher cholesteryl ester (P = 0.004)) that was specific to preeclampsia and independent of maternal gestation. PMID- 27685995 TI - Genome Analysis of Osteosarcoma Progression Samples Identifies FGFR1 Overexpression as a Potential Treatment Target and CHM as a Candidate Tumor Suppressor Gene. AB - Osteosarcoma (OS) is the most common primary malignant tumor of bone, showing complex chromosomal rearrangements but with few known consistent changes. Deeper biological understanding is crucial to find new therapies to improve patient survival. We have sequenced the whole exome of two primary tumors (before and after chemotherapy), one metastatic tumor and a matched normal sample from two OS patients, to identify mutations involved in cancer biology. The metastatic samples were also RNA sequenced. By RNA sequencing we identified dysregulated expression levels of drug resistance- and apoptosis-related genes. Two fusion transcripts were identified in one patient (OS111); the first resulted in p53 inactivation by fusing the first exon of TP53 to the fifth exon of FAM45A. The second fusion joined the two first exons of FGFR1 to the second exon of ZNF343. Furthermore, FGFR1 was amplified and highly expressed, representing a potential treatment target in this patient. Whole exome sequencing revealed large intertumor heterogeneity, with surprisingly few shared mutations. Careful evaluation and validation of the data sets revealed a number of artefacts, but one recurrent mutation was validated, a nonsense mutation in CHM (patient OS106), which also was the mutation with the highest expression frequency (53%). The second patient (OS111) had wild-type CHM, but a downregulated expression level. In a panel of 71 clinical samples, we confirmed significant low expression of CHM compared to the controls (p = 0.003). Furthermore, by analyzing public datasets, we identified a significant association between low expression and poor survival in two other cancer types. Together, these results suggest CHM as a candidate tumor suppressor gene that warrants further investigation. PMID- 27685998 TI - The Global Research Collaboration of Network Meta-Analysis: A Social Network Analysis. AB - BACKGROUND AND OBJECTIVE: Research collaborations in biomedical research have evolved over time. No studies have addressed research collaboration in network meta-analysis (NMA). In this study, we used social network analysis methods to characterize global collaboration patterns of published NMAs over the past decades. METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched (at 9th July, 2015) to include systematic reviews incorporating NMA. Two reviewers independently selected studies and cross-checked the standardized data. Data was analyzed using Ucinet 6.0 and SPSS 17.0. NetDraw software was used to draw social networks. RESULTS: 771 NMAs published in 336 journals from 3459 authors and 1258 institutions in 49 countries through the period 1997-2015 were included. More than three-quarters (n = 625; 81.06%) of the NMAs were published in the last 5-years. The BMJ (4.93%), Current Medical Research and Opinion (4.67%) and PLOS One (4.02%) were the journals that published the greatest number of NMAs. The UK and the USA (followed by Canada, China, the Netherlands, Italy and Germany) headed the absolute global productivity ranking in number of NMAs. The top 20 authors and institutions with the highest publication rates were identified. Overall, 43 clusters of authors (four major groups: one with 37 members, one with 12 members, one with 11 members and one with 10 members) and 21 clusters of institutions (two major groups: one with 62 members and one with 20 members) were identified. The most prolific authors were affiliated with academic institutions and private consulting firms. 181 consulting firms and pharmaceutical industries (14.39% of institutions) were involved in 199 NMAs (25.81% of total publications). Although there were increases in international and inter-institution collaborations, the research collaboration by authors, institutions and countries were still weak and most collaboration groups were small sizes. CONCLUSION: Scientific production on NMA is increasing worldwide with research leadership of Western countries (most notably, the UK, the USA and Canada). More authors, institutions and nations are becoming involved in research collaborations, but frequently with limited international collaborations. PMID- 27685999 TI - Public Health Risks in Urban Slums: Findings of the Qualitative 'Healthy Kitchens Healthy Cities' Study in Kathmandu, Nepal. AB - BACKGROUND: Communities in urban slums face multiple risks to their health. These are shaped by intermediary and structural determinants. Gaining a clear understanding of these determinants is a prerequisite for developing interventions to reduce the health consequences of urban poverty. With 828 million people living in slum conditions, the need to find ways to reduce risks to health has never been greater. In many low income settings, the kitchen is the epicentre of activities and behaviours which either undermine or enhance health. METHODS: We used qualitative methods of semi-structured interviews, observation and participatory workshops in two slum areas in Kathmandu, Nepal to gain women's perspectives on the health risks they faced in and around their kitchens. Twenty one women were interviewed and four participatory workshops with a total of 69 women were held. The women took photographs of their kitchens to trigger discussions. FINDINGS: The main health conditions identified by the women were respiratory disease, gastrointestinal disease and burn injuries. Women clearly understood intermediary (psychosocial, material and behavioural) determinants to these health conditions such as poor ventilation, cooking on open fires, over crowding, lack of adequate child supervision. Women articulated the stress they experienced and clearly linked this to health conditions such as heart disease and uptake of smoking. They were also able to identify protective factors, particularly social capital. Subsequent analysis highlighted how female headed households and those with disabilities had to contend with greater risks to health. CONCLUSIONS: Women living in slums are very aware of the intermediary determinants-material, behavioural and psycho-social, that increase their vulnerability to ill health. They are also able to identify protective factors, particularly social capital. It is only by understanding the determinants at all levels, not just the behavioural, that we will be able to identify appropriate interventions. PMID- 27686000 TI - Different Training-Induced Skeletal Muscle Adaptations in COPD Patients with and without Alpha-1 Antitrypsin Deficiency. AB - BACKGROUND: Pulmonary rehabilitation (PR) improves oxidative capacity of peripheral muscles in patients with chronic obstructive pulmonary disease (COPD). The exercise-induced oxidative skeletal muscle adaptation in COPD patients with inherited alpha-1 antitrypsin deficiency (A1ATD) has not been studied. OBJECTIVES: To compare PR effects on skeletal muscle adaptation in COPD patients with and without A1ATD. METHODS: Nine COPD patients with A1ATD (genotype PiZZ, 6 receiving A1AT augmentation therapy), and 10 'usual' COPD patients (genotype PiMM) performed an incremental cycling test and underwent musculus vastus lateralis biopsies before and after a 3-week PR program including exercise training. RESULTS: PiZZ and PiMM patients improved peak work rate following PR (+9 +/- 11 W, p < 0.05, and +18 +/- 9 W, p < 0.001, between-group difference p < 0.05). PiMM patients increased fibre type I (+8.1%), reduced fibre type IIA ( 2.1%) and hybrid fibre type IIA/IIX proportion (-3.9%). Following PR, PiMM patients also raised mitochondrial signalling proteins PGC-1alpha (4.5-fold), and TFAM (6.4-fold). PiZZ patients had no change in fibre type I but showed a shift of type IIA/IIX (-8.8%) towards fibre type IIA distribution (+8.9%). The capillary to fibre ratio increased by 28% (p < 0.05) in PiZZ, whereas no change was observed in PiMM patients. Linear regression analysis revealed that diffusion capacity and A1AT therapy are predictor variables for myofibre type I response to PR (r2 = 0.684, p < 0.01). CONCLUSIONS: Following a 3-week PR with comparable training modalities, PiMM but not PiZZ patients increased the oxidative myofibre type I proportion. This skeletal muscle adaptation pattern suggests better improvement of exercise capacity in PiMM than in PiZZ patients with COPD. PMID- 27686002 TI - Randomized clinical trial: a pilot study comparing efficacy of low-dose azathioprine and allopurinol to azathioprine on clinical outcomes in inflammatory bowel disease. AB - BACKGROUND: Treating inflammatory bowel diseases (IBD) using thiopurines is effective; however, a high rate of adverse effects and lack of efficacy limit its use. Retrospective studies have suggested that treatment with low-dose thiopurines in combination with allopurinol is associated with higher remission rates and lower incidence of adverse events. AIM: To compare the rates of clinical remission and the rates of adverse events in IBD patients treated with either standard treatment with azathioprine or low-dose azathioprine in combination with allopurinol. METHODS: A prospective, open-label study, randomizing thiopurine-naive IBD patients with normal thiopurine methyltransferase to 24 weeks of treatment with either standard azathioprine dose or low-dose azathioprine and allopurinol. RESULTS: A total of 46 patients with ulcerative colitis or Crohn's disease were randomized. We conducted an intention to treat analysis and found a significant (69.6%) proportion of the patients treated with low-dose azathioprine in combination with allopurinol was in clinical remission without the need for steroid or biologic treatment at week 24 compared to 34.7% of the patients treated with azathioprine monotherapy (RR, 2.10 [95% CI: 1.07-4.11]). In the azathioprine group, 47.8% of the patients compared to 30.4% of the patients in the azathioprine-allopurinol group had to withdraw from the study due to adverse events (RR, 1.47 [95% CI: 0.76-2.85]) Conclusions: This study indicated that by changing the treatment strategy from standard weight based dosing of azathioprine to weight-based low-dose azathioprine in combination with allopurinol, we can increase remission rates in patients with IBD. PMID- 27686001 TI - Aberrant DNA methylations in chondrosarcoma. AB - Chondrosarcoma (CS) is the second most common primary malignant bone tumor. Unlike other bone tumors, CS is highly resistant to conventional chemotherapy and radiotherapy, thus resulting in poor patient outcomes. There is an urgent need to establish alternative therapies for CS. However, the etiology and pathogenesis of CS still remain elusive. Recently, DNA methylation-associated epigenetic changes have been found to play a pivotal role in the initiation and development of human cancers, including CS, by regulating target gene expression in different cellular pathways. Elucidating the mechanisms of DNA methylation alteration may provide biomarkers for diagnosis and prognosis, as well as novel treatment options for CS. We have conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as diagnostic biomarkers, predictors of progression and potential treatment strategies in CS. PMID- 27686003 TI - Why do entrepreneurial mHealth ventures in the developing world fail to scale? AB - Telemedicine is an increasingly common approach to improve healthcare access in developing countries with fledgling healthcare systems. Despite the strong financial, logistical and clinical support from non-governmental organisations (NGOs), government ministries and private actors alike, the majority of telemedicine projects do not survive beyond the initial pilot phase and achieve their full potential. Based on a review of 35 entrepreneurial telemedicine and mHealth ventures, and 17 reports that analyse their operations and challenges, this article provides a narrative review of recurring failure modes, i.e. factors that lead to failure of such venture pilots. Real-world examples of successful and failed ventures are examined for key take-away messages and practical strategies for creating commercial viable telemedicine operations. A better understanding of these failure modes can inform the design of sustainable and scalable telemedicine systems that effectively address the growing healthcare disparities in developing countries. PMID- 27686005 TI - Emerging drugs for the treatment of angina pectoris. AB - INTRODUCTION: Angina pectoris, or symptomatic myocardial ischaemia, reflects an impairment of coronary blood flow, and usually a deficiency of available myocardial energetics. Treatment options vary with the precise cause, which may vary with regards to the roles of increased myocardial oxygen demand versus reduced supply. Traditionally, organic nitrates, beta-adrenoceptor antagonists, and non-dihydropyridine calcium antagonists were the only commonly used prophylactic anti-anginal agents. However, many patients failed to respond adequately to such therapy, and/or were unsuitable for their use. Areas covered: A number of 'new' agents have been shown to represent ancillary forms of prophylactic anti-anginal therapy and are particularly useful in patients who are relatively unsuitable for either percutaneous or surgical revascularisation. These include modulators of myocardial metabolic efficiency, such as perhexiline, trimetazidine and ranolazine, as well as high dose allopurinol, nicorandil and ivabradine. The advantages and disadvantages of these various agents are summarized. Expert opinion: 'Optimal' medical treatment of angina pectoris now includes use of agents primarily intended to reduce risk of infarction (e.g. statins, aspirin, ACE inhibitors). In patients whose angina persists despite the use of 'standard' anti-anginal therapy, and who are not ideal for invasive revascularization options, a number of emerging drugs offer prospects of symptomatic relief. PMID- 27686004 TI - Increased PD-1/STAT1 ratio may account for the survival benefit in decitabine therapy for lower risk myelodysplastic syndrome. AB - Decitabine is an effective therapy for patients with lower risk myelodysplastic syndrome (MDS). However, the mechanisms of decitabine's therapeutic effect are not well established. Forty-four lower risk MDS patients received decitabine therapy. 59.1% patients achieved treatment response, and 53.8% patients who were RBC/platelet-dependent cast off the transfusion burden. The median overall survival (OS) was 19.0 months after decitabine treatment. Moreover, polarization toward type 1 in the CD8 + subset was enhanced, and a significantly increased expression of the PD-1, PD-L1, and PD-1/STAT1 ratio was observed in these lower risk MDS. The patients with amplification of PD-1/STAT1 ratio (2-4) achieved longer OS. Thus, our results suggest that the effect mechanism of decitabine toward lower risk MDS may be the moderate increase of PD-1/STAT1, which contributes to hematopoietic improvement. These findings suggest that a different PD-1-related strategy from those used to treat higher risk patients could be used for lower risk MDS patients. PMID- 27686006 TI - Layered and Pb-Free Organic-Inorganic Perovskite Materials for Ultraviolet Photoresponse: (010)-Oriented (CH3NH3)2MnCl4 Thin Film. AB - Organic-inorganic lead perovskite materials show impressive performance in photovoltaics, photodetectors, light-emitting diodes, lasers, sensors, medical imaging devices, and other applications. Although organic-inorganic lead perovskites have shown good performance in numerous fields, they contain toxic Pb, which is expected to cause environmental pollution in future large-scale applications. Thus, the photoelectric properties of Pb-free organic-inorganic perovskite materials should be developed and studied. In this paper, we report on the photoresponse of Pb-free organic-inorganic hybrid manganese perovskite (CH3NH3)2MnCl4. To the best of our knowledge, this study demonstrates the first time that organic-inorganic hybrid manganese perovskites are used for this type of application. We found that the solution-processed MA2MnCl4 thin film tends to be oriented along the b-axis direction on the TiO2 surface. The evident photoresponse of the FTO/TiO2/MA2MnCl4/carbon electrode devices was observed under 10-30 Hz flashlight frequencies and a 330 nm light beam. This simple, green, and low-cost photoresponsive device is beneficial for the future industrial production of optical recorders and optical memory devices. PMID- 27686007 TI - Facile Stimuli-Responsive Transformation of Vesicle to Nanofiber to Supramolecular Gel via omega-Amino Acid-Based Dynamic Covalent Chemistry. AB - This paper reports an interesting type of self-assembly systems based on dynamic covalent bonds. The systems are pH-responsible and reversible, which could be utilized for controlling the morphology transformation of the assemblies. In alkaline conditions, the amine group of 11-aminoundecanoic acid (AUA) can connect with the aldehyde group of benzaldehyde (BA) or 1-naphthaledhyde (NA) by dynamic covalent bond to form a small organic building block accompanied by the morphological transformation from vesicles to fibers. When pH is lowered to a neutral value, the dynamic covalent bonds (imine bonds) can be hydrolyzed, leading to the dissociation of fibers and appearance of spherical aggregates. The transformation was confirmed reversible as fibers appeared again when the pH was changed back to alkaline value. In addition, a reversibly controlled gel was designed based on the nanofiber formation. NaCl, which is capable of greatly enhance the nanofiber density and cross-linking, was used to induce the growth of free-standing gel from free-flowing nanofiber system, and the resultant gel was proven to be pH-reversible. PMID- 27686010 TI - Corrigendum. PMID- 27686008 TI - New roles for mean platelet volume measurement in the clinical practice? AB - Several hundreds of studies recently investigated mean platelet volume (MPV) as measured by electronic cell counters in a wide variety of acquired diseases, and most of them found that platelet size was significantly increased with respect to healthy subjects. On this basis, it has been suggested that MPV can be used for diagnostic purposes. Moreover, investigation of subjects with arterial thrombosis not only revealed that their platelets were larger than those of controls, but also found that a high MPV predicted poor prognosis. Despite the large amount of available data, the pathogenesis of increased platelet size in these conditions is unclear. In particular, we do not know whether the increased platelet size is the cause or the consequence of thrombosis. Differences in MPV between patients and controls are usually very small and they reach the statistical significance because of the large number of investigated patients and the standardized methodology for MPV measurement. In real life, the wide variability of MPV possibly due to platelet count, sex, age, and ethnicity, as well as the very poor standardization of the methodologies used for MPV measurement, makes it impossible to decide whether an individual patient has normal or instead slightly increased MPV. So, MPV has presently no role in making diagnosis and defining prognosis in any acquired illness. PMID- 27686009 TI - The effect of non-native and non-regional speech testing on a multi-lingual population. AB - OBJECTIVE: This study was conducted to evaluate the speech perception of Malaysian Chinese adults using the Taiwanese Mandarin HINT (MHINT-T) and the Malay HINT (MyHINT). DESIGN: The MHINT-T and the MyHINT were presented in quiet and noise (front, right and left) conditions under headphones. Results for the two tests were compared with each other and with the norms for each test. STUDY SAMPLE: Malaysian Chinese native speakers of Mandarin (N = 58), 18-31 years of age with normal hearing. RESULTS: On average, subjects demonstrated poorer speech perception ability than the normative samples for these tests. Repeated measures ANOVA showed that speech reception thresholds (SRTs) were slightly poorer on the MHINT-T than on the MyHINT for all test conditions. However, normalized SRTs were poorer by 0.6 standard deviations for MyHINT as compared with MHINT-T. CONCLUSIONS: MyHINT and MHINT-T can be used as norm-referenced speech perception measures for Mandarin-speaking Chinese in Malaysia. PMID- 27686011 TI - Dietary macronutrient composition affects hypothalamic appetite regulation in chicks. AB - OBJECTIVE: The objective was to determine the effects of high-protein and high fat diets, and fasting and refeeding, on appetite regulation in chicks. METHODS: Day of hatch chicks were fed one of four diets: basal, high protein (25% crude protein), and 15 and 30% high fat (15 and 30% metabolizable energy derived from soybean oil, respectively), and assigned to one of three treatments at 4 days: (1) access to feed, (2) 3 hours of fasting, or (3) fasting followed by 1 hour of refeeding. The hypothalamus was collected, total RNA isolated, and mRNA abundance measured. RESULTS: Food intake was reduced in chicks fed the high-protein and high-fat diets. Agouti-related peptide, neuropeptide Y (NPY), NPY receptors 1, 2, and 5, melanocortin receptors 3 and 4 (MC3R and 4R, respectively), mesotocin, corticotropin-releasing factor (CRF), and CRF receptor sub-type 2 (CRFR2) mRNAs were greatest in chicks that consumed the basal diet. Refeeding was associated with increased MC3R mRNA in the high-protein diet group. CRFR2 mRNA was increased by fasting and refeeding in chicks that consumed the high-protein diet. DISCUSSION: Food intake and hypothalamic gene expression of some important appetite-associated factors were reduced in chicks fed the high-protein or high fat diets. Fasting and refeeding accentuated several differences and results suggest that the CRF and melanocortin pathways are involved. PMID- 27686012 TI - Interventions to support recovery after domestic and sexual violence in primary care. AB - Experiences of domestic and sexual violence are common in patients attending primary care. Most often they are not identified due to barriers to asking by health practitioners and disclosure by patients. Women are more likely than men to experience such violence and present with mental and physical health symptoms to health practitioners. If identified through screening or case finding as experiencing violence they need to be supported to recover from these traumas. This paper draws on systematic reviews published in 2013-2015 and a further literature search undertaken to identify recent intervention studies relevant to recovery from domestic and sexual violence in primary care. There is limited evidence as to what interventions in primary care assist with recovery from domestic violence; however, they can be categorized into the following areas: first line response and referral, psychological treatments, safety planning and advocacy, including through home visitation and peer support programmes, and parenting and mother-child interventions. Sexual violence interventions usually include trauma informed care and models to support recovery. The most promising results have been from nurse home visiting advocacy programmes, mother-child psychotherapeutic interventions, and specific psychological treatments (Cognitive Behaviour Therapy, Trauma informed Cognitive Behaviour Therapy and, for sexual assault, Exposure and Eye Movement Desensitization and Reprocessing Interventions). Holistic healing models have not been formally tested by randomized controlled trials, but show some promise. Further research into what supports women and their children on their trajectory of recovery from domestic and sexual violence is urgently needed. PMID- 27686013 TI - Metabolic time-course response after resistance exercise: A metabolomics approach. AB - This study analysed the time course of the global metabolic acute response after resistance exercise (RE), with the use of proton nuclear magnetic resonance (1H NMR) spectroscopy. Ten young healthy males performed 4 sets of 10 repetitions at 70% of one-repetition maximum in the leg press and knee extension exercises and had the serum metabolome assessed at 5, 15, 30 and 60 min post-RE. Measurements were also performed 1 h earlier and immediately before the exercises, as an attempt to characterise each participant's serum metabolome at rest. One-way ANOVA was applied and the significance level was set at P <= 0.05. RE promoted an increase in 2-hydroxybutyrate, 2-oxoisocaproate, 3-hydroxyisobutyrate, alanine, hypoxanthine, lactate, pyruvate and succinate concentrations. However, isoleucine, leucine, lysine, ornithine and valine had their concentrations decreased post-RE compared with at rest. This is the first study to show significant changes in serum concentration of metabolites such as 2 oxoisocaproate, 2-hydroxybutyrate, 3-hydroxyisobutyrate, lysine, hypoxanthine and pyruvate post-RE, attesting metabolomics as an interesting approach to advance in the understanding of global RE-induced metabolic changes. Moreover, the present data could influence the time point of blood collection in the future studies that aims to investigate metabolism and exercise. PMID- 27686014 TI - Characteristics and origins of air pollutants in Wuhan, China, based on observations and hybrid receptor models. AB - : To identify the characteristics of air pollutants and factors attributing to the formation of haze in Wuhan, this study analyzed the hourly observations of air pollutants (PM2.5, PM10, NO2, SO2, O3, and CO) from March 1, 2013, to February 28, 2014, and used hybrid receptor models for a case study. The results showed that the annual average concentrations for PM2.5, PM10, NO2, SO2, O3, and CO during the whole period were 89.6 MUg m-3, 134.9 MUg m-3, 54.9 MUg m-3, 32.4 MUg m-3, 62.3 MUg m-3, and 1.1 mg m-3, respectively. The monthly variations revealed that the peak values of PM2.5, PM10, NO2, SO2, and CO occurred in December because of increased local emissions and severe weather conditions, while the lowest values occurred in July mainly due to larger precipitation. The maximum O3 concentrations occurred in warm seasons from May to August, which may be partly due to the high temperature and solar radiation. Diurnal analysis showed that hourly PM2.5, PM10, NO2, and CO concentrations had two ascending stages accompanying by the two traffic peaks. However, the O3 concentration variations were different with the highest concentration in the afternoon. A case study utilizing hybrid receptor models showed the significant impact of regional transport on the haze formation in Wuhan and revealed that the mainly potential polluted sources were located in the north and south of Wuhan, such as Baoding and Handan in Hebei province, and Changsha in Hunan province. IMPLICATIONS: Wuhan city requires a 5% reduction of the annual mean of PM2.5 concentration by the end of 2017. In order to accomplish this goal, Wuhan has adopted some measures to improve its air quality. This work has determined the main pollution sources that affect the formation of haze in Wuhan by transport. We showed that apart from the local emissions, north and south of Wuhan were the potential sources contributing to the high PM2.5 concentrations in Wuhan, such as Baoding and Handan in Hebei province, Zhumadian and Jiaozuo in Henan province, and Changsha and Zhuzhou in Hunan province. PMID- 27686015 TI - Toward an Effective Ebola Virus Vaccine. AB - Long-term control of viral outbreaks requires the use of vaccines to impart acquired resistance and ensuing protection. In the wake of an epidemic, established immunity against a particular disease can limit spread and significantly decrease mortality. Creation of a safe and efficacious vaccine against Ebola virus (EBOV) has proven elusive so far, but various inventive strategies are now being employed to counteract the threat of outbreaks caused by EBOV and related filoviruses. Here, we present a current overview of progress in the field of Ebola virus vaccine development. PMID- 27686016 TI - Resection of Liver Metastases in Colorectal Cancer in the Era of Expanding Systemic Therapy. AB - About 25% of patients with colorectal cancer develop liver metastases after resection of the primary tumor, and surgical resection of the metastases offers the only opportunity for long-term survival. However, only 20% of patients present with resectable disease. Deciding which patients should be offered surgery, and which should receive additional treatment in the form of perioperative chemotherapy, is complex. For the majority of patients who present with technically irresectable liver-limited disease, systemic downsizing chemotherapy offers the only opportunity to reach surgery and potential cure. Molecular analysis of tumor tissue is improving patient stratification, allowing more appropriate treatment selection, but is not yet a regular part of clinical practice. Decision making is limited by a lack of clear prospective evidence, and so multidisciplinary team assessment is essential to optimize outcomes. PMID- 27686017 TI - Oral Combination Therapies for Hepatitis C Virus Infection: Successes, Challenges, and Unmet Needs. AB - The current standard of care for the treatment of hepatitis C virus (HCV) consists of interferon-free direct-acting antiviral (DAA) regimens, including combinations of DAAs and fixed-dose combination pills. DAAs for HCV are likely to be heralded as one of medicine's greatest advancements. Viral eradication rates are pushing 100% for many HCV-infected populations, including patients with HIV/HCV coinfection, decompensated cirrhosis, liver and kidney transplants, and end-stage liver disease. We highlight the greatest successes of combination DAA therapies, discuss the ongoing challenges, and identify the remaining patient subgroups with unmet medical needs. PMID- 27686018 TI - Highly Effective New Treatments for Psoriasis Target the IL-23/Type 17 T Cell Autoimmune Axis. AB - Psoriasis vulgaris, affecting the skin, is one of the most common organ-specific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ~90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis. Thus, psoriasis is a model for the success of a translational-medicine approach based on cellular and molecular dissection of disease pathogenesis in humans. PMID- 27686019 TI - Neprilysin Inhibitors: Emerging Therapy for Heart Failure. AB - Biologically active natriuretic peptides (NPs) are an integral part of cardiac homeostasis as they help to maintain sodium and fluid balance. When homeostasis is perturbed by neurohormonal activation in heart failure, levels of NPs rise in response. Neprilysin (NEP) is a naturally occuring enzyme that breaks down NPs. Scientists have recently discovered a novel pharmacologic agent that combines a NEP inhibitor and an angiotensin receptor blocker. In a large clinical trial, this new drug was found to reduce hospitalization and mortality in systolic heart failure. The challenges of implementing this therapy include patient selection, cost, and risk of side effects including angioedema and Alzheimer's disease. PMID- 27686020 TI - Cardiac Pacing and Defibrillation Devices: Cost and Effectiveness. AB - Implantable cardiac pacing and defibrillation devices are effective and commonly used therapies for patients with cardiac rhythm disorders. Because device implantation is not easily reversible, as well as the high healthcare costs inherent in device use, a clear understanding of the clinical benefits relative to costs is essential for both appropriate clinical use and rational policy making. Cardiac implantable electronic devices (CIEDs) have been among the best investigated therapies in medicine; these devices have been the topic of numerous clinical and economic evaluations during the past 30 years. However, many important questions remain unclarified. We review the evidence supporting the clinical benefits of CIEDs, including effectiveness in extending survival as well as improving quality of life. We also summarize the economic studies that have investigated costs associated with these devices and their overall cost effectiveness, and we highlight important potential areas for future research. PMID- 27686021 TI - Management of Systemic Lupus Erythematosus During Pregnancy. AB - Reproductive issues including contraception, fertility, and pregnancy are important components of the comprehensive care of women with systemic lupus erythematosus (SLE). SLE pregnancies are complicated due to risk for maternal disease exacerbation and potential for fetal and neonatal complications. Pre pregnancy assessment is important to identify patients with severe disease related damage who should avoid pregnancy, counsel patients to conceive when disease has been stable and inactive on appropriate medications, and assess relevant risk factors including renal disease, antiphospholipid antibody, and anti-Ro/SS-A and anti-La/SS-B antibodies. With careful planning, monitoring, and care, most women with SLE can anticipate a successful pregnancy. PMID- 27686022 TI - Checkpoint adaptation: Keeping Cdc5 in the T-loop. PMID- 27686023 TI - Structural and biophysical properties of h-FANCI ARM repeat protein. AB - Fanconi anemia complementation groups - I (FANCI) protein facilitates DNA ICL (Inter-Cross-link) repair and plays a crucial role in genomic integrity. FANCI is a 1328 amino acids protein which contains armadillo (ARM) repeats and EDGE motif at the C-terminus. ARM repeats are functionally diverse and evolutionarily conserved domain that plays a pivotal role in protein-protein and protein-DNA interactions. Considering the importance of ARM repeats, we have explored comprehensive in silico and in vitro approach to examine folding pattern. Size exclusion chromatography, dynamic light scattering (DLS) and glutaraldehyde crosslinking studies suggest that FANCI ARM repeat exist as monomer as well as in oligomeric forms. Circular dichroism (CD) and fluorescence spectroscopy results demonstrate that protein has predominantly alpha- helices and well-folded tertiary structure. DNA binding was analysed using electrophoretic mobility shift assay by autoradiography. Temperature-dependent CD, Fluorescence spectroscopy and DLS studies concluded that protein unfolds and start forming oligomer from 30 degrees C. The existence of stable portion within FANCI ARM repeat was examined using limited proteolysis and mass spectrometry. The normal mode analysis, molecular dynamics and principal component analysis demonstrated that helix-turn helix (HTH) motif present in ARM repeat is highly dynamic and has anti-correlated motion. Furthermore, FANCI ARM repeat has HTH structural motif which binds to double-stranded DNA. PMID- 27686024 TI - Interaction between hippocampal serotonin and cannabinoid systems in reactivity to spatial and object novelty detection. AB - Functional interaction between cannabinoid and serotonin neuronal systems have been reported in different tasks related to memory assessment. The present study investigated the effect of serotonin 5-HT4 agents into the dorsal hippocampus (the CA1 region) on spatial and object novelty detection deficits induced by activation of cannabinoid CB1 receptors (CB1Rs) using arachidonylcyclopropylamide (ACPA) in a non-associative behavioral task designed to forecast the ability of rodents to encode spatial and non-spatial relationships between distinct stimuli. Post-training, intra-CA1 microinjection of 5-HT4 receptor agonist RS67333 or 5 HT4 receptor antagonist RS23597 both at the dose of 0.016MUg/mouse impaired spatial memory, while cannabinoid CB1R antagonist AM251 (0.1MUg/mouse) facilitated object novelty memory. Also, post-training, intraperitoneal administration of CB1R agonist ACPA (0.005-0.05mg/kg) impaired both memories. However, a subthreshold dose of RS67333 restored ACPA response on both memories. Moreover, a subthreshold dose of RS23597 potentiated ACPA (0.01mg/kg) and reversed ACPA (0.05mg/kg) responses on spatial memory, while it potentiated ACPA response at the dose of 0.005 or 0.05mg/kg on object novelty memory. Furthermore, effective dose of AM251 restored ACPA response at the higher dose. AM251 blocked response induced by combination of RS67333 or RS23597 and the higher dose of ACPA on both memories. Our results highlight that hippocampal 5-HT4 receptors differently affect cannabinoid signaling in spatial and object novelty memories. The inactivation of CB1 receptors blocks the effect of 5-HT4 agents into the CA1 region on memory deficits induced by activation of CB1Rs via ACPA. PMID- 27686025 TI - Lack of effect of chronic ketamine administration on depression-like behavior and frontal cortex autophagy in female and male ICR mice. AB - The acute antidepressant effects of ketamine provide hope for the development of a fast acting approach to treat depression but the consequences of chronic treatment with ketamine are still unclear. One theory regarding the acute effect is that ketamine acts through activation of mTOR but chronic activation of mTOR may lead to reduced autophagy and reduced autophagy could have negative consequences on neuronal plasticity and survival and on affect. To study the interaction between chronic ketamine administration, autophagy and depression the present study tested the effects of 3 weeks daily administration of 5 or 10mg/kg ketamine in both female and male ICR mice on behavior in the open field and the forced swim test and on frontal cortex levels of beclin-1 and p62, two proteins that serve as markers of autophagy. The results show that acute administration of ketamine results in an antidepressant-like effect in the FST, chronic ketamine had no effects in the behavioral tests. There was no difference in the acute or chronic groups between female and male mice. Additionally, chronic ketamine did not alter frontal cortex levels of autophagy markers. The present study suggests that in ICR mice, chronic ketamine does not have the same clear effects that are seen after acute treatment. The lack of difference between females and males and the lack of effects on autophagy after chronic treatment is discussed. PMID- 27686027 TI - Parkinson's disease psychosis as a serotonin-dopamine imbalance syndrome. AB - Parkinson's disease psychosis (PDP) is theoretically a serotonin-dopamine imbalance syndrome due to disruption of the normal balance between the serotonergic and dopaminergic neurotransmitter systems in key brain circuits. PMID- 27686026 TI - The role of neuropeptide CART in the lateral hypothalamic-ventral tegmental area (LH-VTA) circuit in motivation. AB - Rats with electrode implanted in the lateral hypothalamus (LH)-medial forebrain bundle (MFB) area actively engage in intracranial self-stimulation (ICSS). However, the neuronal substrate that translates the electrical pulses into the neural signals, and integrates the information with mesolimbic reward system, has remained elusive. We test the hypothesis that the cocaine- and amphetamine regulated transcript (CART) neurons in the LH-MFB area may support this function. The ICSS activity via an electrode in LH-MFB area was facilitated by CART (55 102) peptide stereotaxically injected in the lateral ventricle or posterior ventral tegmental area (pVTA), but attenuated by CART antibody. While the ICSS experience seems to activate CART cells in the LH, the pVTA showed significant increment in the CART fiber terminals on the dopamine cells, increase in tyrosine hydroxylase (TH)-immunoreactivity, and CART and synaptophysin colabeled elements. Neuronal tracing experiments revealed that CART cells of the LH-MFB region project to the pVTA. The rats with stereotaxically implanted cannulae in pVTA avidly self-infused CART (55-102) suggesting a role for the peptide in motivation, however, CART (1-39) was ineffective. CART self-infusing activity was inhibited by dopamine D1 receptors antagonist, given directly in the nucleus accumbens shell (AcbSh). The rats trained to self-administer CART (55-102) showed enhanced TH immunoreactivity in the cells of pVTA and fibers in AcbSh. We suggest that CART neurons of the LH-MFB area may play a role in conveying reward information to the mesolimbic dopamine neurons, which in turn may arouse the goal directed behavior. PMID- 27686030 TI - Promoting academic careers of women in medicine. PMID- 27686028 TI - Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials. AB - OBJECTIVES: To meta-analytically summarize lamotrigine's effectiveness and safety in unipolar and bipolar depression. METHODS: We conducted systematic PubMed and SCOPUS reviews (last search =10/01/2015) of randomized controlled trials comparing lamotrigine to placebo or other agents with antidepressant activity in unipolar or bipolar depression. We performed a random-effects meta-analysis of depression ratings, response, remission, and adverse effects calculating standardized mean difference (SMD) and risk ratio (RR) +/-95% confidence intervals (CIs). RESULTS: Eighteen studies (n=2152, duration=9.83 weeks) in patients with unipolar depression (studies=4, n=187; monotherapy vs lithium=1, augmentation of antidepressants vs placebo=3) or bipolar depression (studies=14, n=1965; monotherapy vs placebo=5, monotherapy vs lithium or olanzapine+fluoxetine=2, augmentation of antidepressants vs placebo=1, augmentation of mood stabilizers vs placebo=3, augmentation of mood stabilizers vs trancylpromine, citalopram, or inositol=3) were meta-analyzed. Lamotrigine's efficacy for depressive symptoms did not differ significantly in monotherapy vs augmentation studies (vs. placebo: p=0.98, I2=0%; vs active agents: p=0.48, I2=0%) or in unipolar vs bipolar patients (vs placebo: p=0.60, I2=0%), allowing pooling of each placebo-controlled and active-controlled trials. Lamotrigine outperformed placebo regarding depressive symptoms (studies=11, n=713 vs n=696; SMD=-0.15, 95% CI=-0.27, -0.02, p=0.02, heterogeneity: p=0.24) and response (after removing one extreme outlier; RR=1.42, 95% CI=1.13-1.78; p=0.003, heterogeneity: p=0.08). Conversely, lamotrigine did not differ regarding efficacy on depressive symptoms, response, or remission from lithium, olanzapine+fluoxetine, citalopram, or inositol (studies=6, n=306 vs n=318, p values=0.85-0.92). Adverse effects and all-cause/specific-cause discontinuation were similar across all comparisons. CONCLUSIONS: Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol. PMID- 27686029 TI - Efficacy and safety of dextrose-insulin in unmasking non-diagnostic Brugada ECG patterns. AB - BACKGROUND: Typical diagnostic, coved-type 1, Brugada ECG patterns fluctuate spontaneously over time with a high proportion of non-diagnostic ECG patterns. Insulin modulates ion transport mechanisms and causes hyperpolarization of the resting potential. We report our experience with unmasking J-ST changes in response to a dextrose-insulin test. METHODS: Nine patients, mean age 40.5+/ 19.4years (range: 15-65years), presented initially with a non-diagnostic ECG pattern, which was suggestive of Brugada syndrome (group I). They were compared with 10 patients with normal ECG patterns (group II). Participants received an infusion of 50g of 50% dextrose, followed by 10IU of intravenous regular insulin. Positive changes were defined by conversion to a diagnostic ECG pattern. RESULTS: The dextrose-insulin test was positive in six of seven (85.7%) patients (kappa 0.79, p=0.02) that was confirmed with a pharmacologic test (kappa 1, p=0.003). One had an inconclusive test, and two with a negative test had an early repolarization ECG pattern. All subjects in group II had a negative test (p<0.01). The maximum changes of the J-ST segment were observed 41.3+/ 31.4minutes (range 3-90minutes) after dextrose-insulin infusion. One patient had monomorphic ventricular bigeminy without spontaneous or induced ventricular fibrillation. CONCLUSION: Changes in J-ST segment in the Brugada syndrome are influenced by glucose-insulin, and this report reproduces and supports the efficacy and safety of this metabolic test in the differential diagnosis of patients with non-diagnostic ECG patterns. PMID- 27686031 TI - [Infectious and neoplasic complications after kidney transplantation]. AB - Infections and malignancies are the expected complications of immunosuppressive therapy, which non-specifically impairs cellular and humoral immune responses in renal transplant recipients. Infections were usually frequent and severe during the early post-transplant period (first year). Recent diagnostic methods (molecular biology) and availability of new antivirals, antifungal and antibiotic drugs made rapid diagnosis and systematic preventive strategies much easier and this resulted in a significant reduction of infections and infectious death in this population. However, new infectious agents like BK polyomavirus, hepatitis E virus, parvovirus (as well as Chigunkunya, West Nile and others in particular areas) were recently recognized as responsible of aggressive infections in the immunocompromised host. Malignancies are also common after transplantation, due to the intensity and duration of immunosuppression. Skin cancers and lymphoproliferative disorders are the most common and are undoubtedly caused by viral infections, but incidence of non-skin cancers is also increased. After reduction of immunosuppression, treatment is similar to non-transplant patients: Results are usually poor and cancer is now the third cause of death in transplant recipients. Due to their anti-proliferative and anti-tumoral properties, incidence of de novo cancer significantly decreased in patients receiving mTor inhibitors as maintenance immunosuppression; furthermore, in patients already diagnosed with Kaposi sarcoma or recurrent skin cancers, introduction of mTor was associated with stabilisation and/or regression of malignant lesions. PMID- 27686032 TI - [Beware, polyarteritis nodosa still exists in nephrology!] AB - Renal involvement of systemic vasculitides is an emergency in nephrology. Although it has become very rare, the diagnosis of polyarteritis nodosa must be considered in some patients. A 70-year-old patient, previously healthy, presented with acute renal failure and malignant hypertension and abundant albuminuria. Subcutaneous nodule, orchitis and mononeuritis appeared subsequently. The search for auto-immunity or viral infection was negative. Markers of thrombotic microangiopathy, present initially, resolved after blood pressure control. After a renal computed tomography with contrast medium injection was considered normal, without any micro-aneurysm, a renal biopsy was performed. It showed vascular lesions and glomerular ischemia. It was complicated by hemorragic shock after 36hours. The diagnosis of periarteritis nodosa was finally made after arterial angiography showed millimetric renal micro-aneurysms. In case of systemic vasculitis with renal involvement, periarteritis nodosa must be part of differential diagnosis, especially in case of malignant hypertension, subcutaneous nodosa and orchitis, and despite albuminuria. This implies the search for micro-aneurysms with arterial angiography, and the contraindication of renal biopsy, associated with a high risk of severe hemorrhage. Periarteritis nodosa still exists in nephrology, even without hepatitis B infection. The association of acute renal failure with medium vessel vasculitis, with negative ANCA, must alert the nephrologist and lead to arterial angiography not to renal biopsy. PMID- 27686033 TI - [Inadequacy of the African-American ethnic factor to estimate glomerular filtration rate in an African general population: Results from Cote d'Ivoire]. AB - Glomerular filtration rate (GFR) estimation is fundamental in clinical nephrology. It is usually estimated from equations based on serum creatinine. An ethnic factor is currently recommended for the black population for the two most used equations, i.e. the Chronic Kidney Disease-Epidemiology Collaboration (CKD EPI) and Modification of Diet in Renal Disease (MDRD) study equations. However, these factors were determined from African-American subjects. Therefore, their use in the African subject (non-American) remained questionable. To date, no data are available in West Africa for the adequacy of these ethnic coefficients, as compared with a measurement of GFR by a reference method. One hundred and twenty subjects of the general population, with no nephrologic history, were included in the study (60 women and 60 men). GFR was determined by a reference method, i.e. the plasma clearance of iohexol. The performance (bias, standard deviation, accuracy within 30%) of both CKD-EPI and MDRD study equations were assessed with and without the ethnic factors. GFR measurements (mGFR) according iohexol reference method were 100+/-19mL/min/1.73m2. The MDRD study equation without any ethnic factor underestimates mGFR by -9+/-16mL/min/1.73m2, whereas the MDRD study equation with the ethnic factor overestimates mGFR by +10+/-18mL/min/1.73m2. Regarding the CKD-EPI equation, bias and accuracy within 30% are significantly better without than with the ethnic factor. Indeed, bias is 16+/-2mL/min/1.73m2 and 18+/-17mL/min/1.73m2 and accuracy is 93% and 76%, without and with the ethnic factor, respectively (P<0.0001). We show for the first time in African population that the performance of CKD-EPI and MDRD study equations is significantly better, in a general population, without the "African-American" ethnic factor. The "African-American" ethnic factor should not be applied in West Africa. PMID- 27686034 TI - Lipid droplets in the ovine uterus during the estrous cycle: Effects of nutrition, arginine, and FSH. AB - The aim of this study was to evaluate lipid droplet (LD) expression in uteri of FSH-treated or nontreated sheep administered with arginine (Arg) or vehicle (saline, Sal) and fed a control (C), excess (overfed, O) or restricted (underfed, U) diet. In experiment 1, ewes from each diet were randomly assigned to Arg or Sal treatments administered three times daily starting on Day 0 of the first estrous cycle until blood sample and uterine tissue collection at the early- or mid-luteal phase of the second estrous cycle or the late-luteal phase of the first estrous cycle. In experiment 2, ewes were injected twice daily with FSH on Days 13 to 15 of the first estrous cycle, and blood samples and uterine tissue were collected at the early- and mid-luteal phases of the second estrous cycle. Cryopreserved in optimum cutting temperature (OCT) compound, cross-sections of uterine horn were stained with boron-dipyrromethene (BODIPY; marker of LDs) followed by 4',6-diamidino-2-phenylindole (DAPI) staining and image analysis to determine the proportion (%) of area occupied by LD in luminal epithelium (LE) and endometrial glands (EGs). Control ewes maintained, O ewes gained, and U ewes lost body weight during the experiments. Serum progesterone concentration was not affected by nutritional plane or Arg treatment and was 5.5-fold greater in FSH- than Sal-treated ewes. LDs were detected in LE and superficial EG (close to LE) but not deep EG, or other uterine compartments, and area occupied by LD was greater in LE than in EG. In experiment 1, in LE and EG, area occupied by LDs was greater in C than in O or U; greater in Arg than in Sal; and greater at the late , less at mid-, and least at early-luteal phases. In experiment 2, in LE and EG, area occupied by LDs was greater at mid- than in early-luteal phase. Comparison of data from FSH-treated and nontreated ewes (e.g., experiment 1 vs. experiment 2) demonstrated that FSH increased the area occupied by LD in LE and EG regardless of diet. Interactions between FSH treatment, stage of the estrous cycle, and plane of nutrition demonstrated that FSH increased the area occupied by LD in LE and EG at the mid-luteal phase in O and U. Thus, LDs are differentially distributed in uterine compartments, and area occupied by LD in endometrium is affected by nutritional plane, Arg or FSH, and stage of the estrous cycle. Such changes in dynamics of LD in the endometrium during the estrous cycle indicate their specific role in uterine functions. PMID- 27686035 TI - Lipogenesis in a wing-polymorphic cricket: Canalization versus morph-specific plasticity as a function of nutritional heterogeneity. AB - The influence of variable nutritional input on life history adaptation is a central, but incompletely understood aspect of life history physiology. The wing polymorphic cricket, Gryllus firmus, has been extensively studied with respect to the biochemical basis of life history adaptation, in particular, modification of lipid metabolism that underlies the enhanced accumulation of lipid flight fuel in the dispersing morph [LW(f)=long wings with functional flight muscles] relative to the flightless (SW=short-winged) morph. To date, biochemical studies have been undertaken almost exclusively using a single laboratory diet. Thus, the extent to which nutritional heterogeneity, likely experienced in the field, influences this key morph adaptation is unknown. We used the experimental approach of the Geometric Framework for Nutrition and employed 13 diets that differed in the amounts and ratios of protein and carbohydrate to assess how nutrient amount and balance affects morph-specific lipid biosynthesis. Greater lipid biosynthesis and allocation to the soma in the LW(f) compared with the SW morph (1) occurred across the entire protein-carbohydrate landscape and (2) is likely an important contributor to elevated somatic lipid in the LW(f) morph across the entire protein-carbohydrate landscape. Nevertheless, dietary carbohydrate strongly affected lipid biosynthesis in a morph-specific manner (to a greater degree in the LW(f) morph). Lipogenesis in the SW morph may be constrained due to its more limited lipid storage capacity compared to the LW(f) morph. Elevated activity of NADP+-isocitrate dehydrogenase (NADP+-IDH), an enzyme that produces reducing equivalents for lipid biosynthesis, was correlated with and may be an important cause of the increased lipogenesis in the LW(f) morph across most, but not all regions of the protein-carbohydrate landscape. By contrast, ATP-citrate lyase (ACL), an enzyme that catalyzes the first step in the pathway of fatty acid biosynthesis, showed complex morph-specific patterns of activity that were strongly contingent upon diet. Morph-specific patterns of NADP+-IDH and ACL activities across the nutrient landscape were much more complex than expected from previous studies on a single diet. Collectively, our results indicate that the biochemical basis of an important life history adaptation, morph-specific lipogenesis, can be canalized in the face of substantial nutritional heterogeneity. However, in some regions of the protein-carbohydrate landscape, it is strongly modulated in a morph-specific manner. PMID- 27686036 TI - Fetal fibronectin testing in threatened preterm labor: time to stop. PMID- 27686037 TI - Pregnancy as a window to future health: short-term costs and consequences. PMID- 27686038 TI - A high-throughput bioimaging study to assess the impact of chitosan-based nanoparticle degradation on DNA delivery performance. AB - : By using imaging flow cytometry as a powerful statistical high-throughput technique we investigated the impact of degradation on the biological performance of trimethyl chitosan (TMC)-based nanoparticles (NPs). In order to achieve high transfection efficiencies, a precise balance between NP stability and degradation must occur. We altered the biodegradation rate of the TMC NPs by varying the degree of acetylation (DA) of the polymer (DA ranged from 4 to 21%), giving rise to NPs with different enzymatic degradation profiles. While this parameter did not affect NP size, charge or ability to protect plasmid DNA, NPs based on TMC with an intermediate DA (16%) showed the highest transfection efficiency. Subsequently, by means of a single quantitative technique, we were able to follow, for each tested formulation, major steps of the NP-mediated gene delivery process - NP cell membrane association, internalization and intracellular trafficking, including plasmid DNA transport towards the nucleus. NP cytotoxicity was also possible to determine by quantification of cell apoptosis. Overall, the obtained data revealed that the biodegradation rate of these NPs affects their intracellular trafficking and, consequently, their efficiency to transfect cells. Thus, one can use the polymer DA to modulate the NPs towards attaining different degradation rates and tune their bioactivity according to the desired application. Furthermore, this novel technical approach revealed to be a valuable tool for the initial steps of nucleic acid vector design. STATEMENT OF SIGNIFICANCE: By changing the biodegradation rate of trimethyl chitosan-based nanoparticles (NPs) one was able to alter the NP ability to protect or efficiently release DNA and consequently, to modulate their intracellular dynamics. To address the influence of NP degradation rate in their transfection efficiency we took advantage of imaging flow cytometry, a high-throughput bioimaging technique, to unravel some critical aspects about NP formulation such as the distinction between internalized versus cell-associated/adsorbed NP, and even explore NP intracellular localization. Overall, our work provides novel information about the importance of vector degradation rate for gene delivery into cells, as a way to tune gene expression as a function of the desired application, and advances novel approaches to optimize nanoparticle formulation. PMID- 27686039 TI - Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan. AB - : Contaminated or infected bone defects remain serious challenges in clinical trauma and orthopaedics, and a bone substitute with both osteoconductivity and antibacterial properties represents an improvement for treatment strategy. In this study, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) was grafted to 3D-printed scaffolds composed of polylactide-co glycolide (PLGA) and hydroxyapatite (HA), in order to design bone engineering scaffolds endowed with antibacterial and osteoconductive properties. We found that both the PLGA/HA/HACC and PLGA/HACC composite scaffolds decreased bacterial adhesion and biofilm formation under in vitro and in vivo conditions. Additionally, ATP leakage assay indicated that immobilizing HACC on the scaffolds could effectively disrupt microbial membranes. Using human bone marrow-derived mesenchymal stem cells (hBMSCs), we demonstrated that HA incorporated scaffolds, including PLGA/HA and PLGA/HA/HACC, favoured cell attachment, proliferation, spreading and osteogenic differentiation compared to HA-free PLGA or PLGA/HACC scaffolds. Finally, an in vivo biocompatibility assay conducted on rats, showed that HA incorporated scaffolds (including PLGA/HA and PLGA/HA/HACC scaffolds) exhibited good neovascularization and tissue integration. Taken together, our findings support the approach for developing porous PLGA/HA/HACC composite scaffold with potential clinical application in the treatment of infected bone. STATEMENT OF SIGNIFICANCE: Although plenty of conductive scaffold biomaterials have been exploited to improve bone regeneration under infection, potential tissue toxicity under high concentration and antibiotic-resistance are their main deficiencies. This study indicated that HACC-grafted PLGA/HA composite scaffold prepared using an innovative 3D-printing technique and covalent grafting strategy showed significantly enhanced antibacterial activities, especially against the antibiotic-resistant strains, together with good osteogenic activity and biocompatibility. Therefore, it provides an effective porous composite scaffold to combat the infected bone defect in clinic with decreased risks of bacterial resistance and open a feasible strategy for the modification of scaffold interfaces involved in the bone regeneration and anti-infection. PMID- 27686040 TI - In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds. AB - : Spatiotemporally controlled release of growth factors (GFs) is critical for regenerative processes such as angiogenesis. A common strategy is to encapsulate the GF within hydrogels, with release being controlled via diffusion and/or gel degradation (i.e., hydrolysis and/or proteolysis). However, simple encapsulation strategies do not provide spatial or temporal control of GF delivery, especially non-invasive, on-demand controlled release post implantation. We previously demonstrated that fibrin hydrogels, which are widely used in tissue engineering and GF delivery applications, can be doped with perfluorocarbon emulsion, thus yielding an acoustically responsive scaffold (ARS) that can be modulated with focused ultrasound, specifically via a mechanism termed acoustic droplet vaporization. This study investigates the impact of ARS and ultrasound properties on controlled release of a surrogate payload (i.e., fluorescently-labeled dextran) and fibrin degradation in vitro and in vivo. Ultrasound exposure (2.5MHz, peak rarefactional pressure: 8MPa, spatial peak time average intensity: 86.4mW/cm2), generated up to 7.7 and 21.7-fold increases in dextran release from the ARSs in vitro and in vivo, respectively. Ultrasound also induced morphological changes in the ARS. Surprisingly, up to 2.9-fold greater blood vessel density was observed in ARSs compared to fibrin when implanted subcutaneously, even without delivery of pro-angiogenic GFs. The results demonstrate the potential utility of ARSs in generating controlled release for tissue regeneration. STATEMENT OF SIGNIFICANCE: Simple encapsulation of a molecular payload within a conventional hydrogel scaffold does not provide spatial or temporal control of payload release. Yet, spatiotemporally controlled release of bioactive payloads is critical for tissue regeneration, which often utilizes hydrogel scaffolds to facilitate processes such as angiogenesis. This work investigates the design and performance (both in vitro and in vivo) of hydrogel scaffolds where release of a fluorescent payload is non-invasively and spatiotemporally-controlled using focused ultrasound. We also quantitatively characterize the degradation and vascularization of the scaffolds. Our results may be of interest to groups working on controlled release strategies for implants, especially within the field of tissue engineering. PMID- 27686042 TI - Biodegradable functional polycarbonate micelles for controlled release of amphotericin B. AB - : Amphotericin B (AmB), a poorly soluble and toxic antifungal drug, was encapsulated into polymeric micelles self-assembled from phenylboronic acid functionalized polycarbonate/PEG (PEG-PBC) and urea-functionalized polycarbonate/PEG (PEG-PUC) diblock copolymers via hydrogen-bonding, boronate ester bond, and/or ionic interactions between the boronic acid group in the micellar core and amine group in AmB. Three micellar formulations were prepared: AmB/B micelles using PEG-PBC, AmB/U micelles using PEG-PUC and AmB/B+U mixed micelles using 1:1molar ratio of PEG-PBC and PEG-PUC. The average particle sizes of the micelles were in the range of 54.4-84.8nm with narrow size distribution and zeta potentials close to neutral. UV-Vis absorption analysis indicated that AmB/B micelles significantly reduced AmB aggregation status due to the interactions between AmB and the micellar core, while Fungizone(r) and AmB/U micelles had no effect. AmB/B+U mixed micelles exerted an intermediate effect. Both AmB/B micelles and AmB/B+U mixed micelles showed sustained drug release, with 48.6+/-2.1% and 59.2+/-1.8% AmB released respectively after 24hunder sink conditions, while AmB/U micelles displayed a burst release profile. All AmB loaded micelles showed comparable antifungal activity to free AmB or Fungizone(r), while AmB/B micelles and AmB/B+U mixed micelles were much less hemolytic than other formulations. Histological examination showed that AmB/B and AmB/B+U micelles led to a significantly lower number of apoptotic cells in the kidneys compared to Fungizone(r), suggesting reduced nephrotoxicity of the micellar formulations in vivo. These phenylboronic acid-functionalized polymeric micelle systems are promising drug carriers for AmB to reduce non-specific toxicities without compromise in antifungal activity. STATEMENT OF SIGNIFICANCE: There is a pressing need for a novel and cost-effective delivery system to reduce the toxicity induced by the antifungal agent, amphotericin B (AmB). In this study, phenylboronic acid-functionalized polycarbonate/PEG diblock copolymers were used to fabricate micelles for improved AmB-micelle interaction via the manipulation of hydrogen-bonding, boronate ester bond, ionic and hydrophobic interactions. Compared to free AmB and Fungizone(r), the resultant micellar systems displayed improved stability while reducing non-specific toxicities without a compromise in antifungal activity. These findings demonstrate the potential of biodegradable functional polycarbonate micellar systems as promising carriers of AmB for the treatment of systemic fungal infections. PMID- 27686041 TI - Direct silanization of zirconia for increased biointegration. AB - : High-performance bioinert ceramics such as zirconia have been used for biomedical devices since the early seventies. In order to promote osseointegration, the historical solution has been to increase the specific surface of the implant through roughness. Nevertheless these treatments on ceramics may create defects at the surface, exposing the material to higher chances of early failure. In zirconia, such treatments may also affect the stability of the surface. More recently, the interest of improving osseointegration of implants has moved the research focus towards the actual chemistry of the surface. Inspired by this, we have adapted the current knowledge and techniques of silica functionalization and applied it to successfully introduce 3-aminopropyldimethylethoxy silane (APDMES) directly on the surface of zirconia (3Y-TZP). We used plasma of oxygen to clean the surface and promote hydroxylation of the surface to increase silane density. The samples were extensively characterized by means of X-ray photoelectron spectroscopy (XPS) and contact angle, mechanically tested and its cytotoxicity was evaluated through cell adhesion and proliferation tests. Additionally, aging was studied to discard negative effects of the treatment on the stability of the tetragonal phase. No adverse effect was found on the mechanical response of treated samples. In addition, plasma-treated samples exhibited an unexpectedly higher resistance to aging. Finally, silane density was 35% lower than the one reported in literature for silica. However cells displayed a qualitatively higher spreading in opposition to the rounder appearance of cells on untreated zirconia. These results lay the foundations for the next generation of zirconia implants with biologically friendlier surfaces. STATEMENT OF SIGNIFICANCE: The use of zirconia based ceramics in biomedical devices is broad and well accepted, especially in dental implants. However, they do not bond naturally to bone, therefore to ensure fixation surgeons typically rely on roughness at different scales, or on cements. Alternatively in this work we present a new perspective of surface modification through chemistry to enhance the interaction between surface and biological environment, without the downsides of roughness. This surface treatment is proposed for zirconia, which allowed a direct silanization of its surface and a higher cell attachment. The results of this research may open the possibility for the next generation of bioinert ceramic implants with more advanced tailored surfaces for increased osseointegration. PMID- 27686043 TI - Psychosocial Influences on Acceptability and Feasibility of Salivary Cortisol Collection From Community Samples of Children. AB - Salivary cortisol is considered to be a safe and noninvasive measure of hypothalamic-pituitary-adrenal axis functioning, and is a commonly measured biomarker of the human stress response in pediatric research. However, cortisol is highly variable and sensitive to a wide range of factors, creating a challenge for reliable salivary cortisol collection in the community setting. Furthermore, the acceptability of salivary cortisol collection in community samples of children is largely unknown. The purpose of this integrative review was to investigate current evidence on the acceptability and feasibility of salivary cortisol collection in community samples of children. In an analysis framed by the Theory of Planned Behavior, data extracted from 31 studies revealed six categories of psychosocial influences on acceptability and feasibility: uncertainty and misconceptions, cultural and ethnic values, family rules and values, difficulty following protocols and procedures, burden of multiple samples, and child refusal or resistance. Further research is required to fully understand the factors that influence acceptability and feasibility of salivary cortisol collection in community samples of children. Understanding individual, family, and community perceptions of biobehavioral research will lead to more culturally sensitive and feasible community-based research methods. (c) 2016 Wiley Periodicals, Inc. PMID- 27686044 TI - Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy. AB - BACKGROUND: Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). METHODS: We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6MUg/mL, lathosterol 1.4MUg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low lathosterol. Endpoint was a composite of cardiac events, including cardiac related death, hospitalization for worsening heart failure, and lethal arrhythmia. RESULTS: Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol <153mg/dL was a best cut-off value for discrimination of the D subset. CONCLUSIONS: The combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM. PMID- 27686046 TI - Columnar structured FePt films epitaxially grown on large lattice mismatched intermediate layer. AB - The microstructure and magnetic properties of the FePt films grown on large mismatched ZrN (15.7%) intermediate layer were investigated. With using ZrN intermediate layer, FePt 10 nm films exhibited (001) texture except for some weaker FePt (110) texture. Good epitaxial relationships of FePt (001) <100>//ZrN (001) <100>//TiN (001) <100> among FePt and ZrN/TiN were revealed from the transmission electron microscopy (TEM) results. As compared with TiN intermediate layer, although FePt-SiO2-C films grown on ZrN/TiN intermediate layer showed isotropic magnetic properties, the large interfacial energy and lattice mismatch between FePt and ZrN would lead to form columnar structural FePt films with smaller grain size and improved isolation. By doping ZrN into the TiN layer, solid solution of ZrTiN was formed and the lattice constant is increased comparing with TiN and decreased comparing with ZrN. Moreover, FePt-SiO2-C films grown on TiN 2 nm-20 vol.% ZrN/TiN 3 nm intermediate layer showed an improved perpendicular magnetic anisotropy. Simultaneously, columnar structure with smaller grain size retained. PMID- 27686047 TI - Stroke: Remote white matter integrity influences cognitive function after stroke. PMID- 27686045 TI - The influence of facility and home pen design on the welfare of the laboratory housed dog. AB - We have an ethical and scientific obligation to Refine all aspects of the life of the laboratory-housed dog. Across industry there are many differences amongst facilities, home pen design and husbandry, as well as differences in features of the dogs such as strain, sex and scientific protocols. Understanding how these influence welfare, and hence scientific output is therefore critical. A significant proportion of dogs' lives are spent in the home pen and as such, the design can have a considerable impact on welfare. Although best practice guidelines exist, there is a paucity of empirical evidence to support the recommended Refinements and uptake varies across industry. In this study, we examine the effect of modern and traditional home pen design, overall facility design, husbandry, history of regulated procedures, strain and sex on welfare indicating behaviours and mechanical pressure threshold. Six groups of dogs from two facilities (total n=46) were observed in the home pen and tested for mechanical pressure threshold. Dogs which were housed in a purpose-built modern facility or in a modern design home pen showed the fewest behavioural indicators of negative welfare (such as alert or pacing behaviours) and more indicators of positive welfare (such as resting) compared to those in a traditional home pen design or traditional facility. Welfare indicating behaviours did not vary consistently with strain, but male dogs showed more negative welfare indicating behaviours and had greater variation in these behaviours than females. Our findings showed more positive welfare indicating behaviours in dogs with higher mechanical pressure thresholds. We conclude that factors relating to the design of home pens and implementation of Refinements at the facility level have a significant positive impact on the welfare of laboratory-housed dogs, with a potential concomitant impact on scientific endpoints. PMID- 27686048 TI - Huntington disease: Selective deactivation of Huntington disease mutant allele by CRISPR-Cas9 gene editing. PMID- 27686050 TI - Herceptin-functionalized pure paclitaxel nanocrystals for enhanced delivery to HER2-postive breast cancer cells. AB - The objective of this study was to prepare Herceptin (HCT)-functionalized paclitaxel nanocrystals and evaluated their cell-specific interactions, cellular accumulation, and growth inhibition in HER2-positve breast cancer cells as a tumor-targeted delivery module. Paclitaxel (PTX) was fabricated in the form of nanocrystals (PNCs) by a sono-precipitation method, and HCT were coated using a facile non-covalent method (PNCs-HCT). Our results showed that the PNCs-HCT were stable for at least 1month at 4 degrees C with no noticeable desorption of HCT. The release test showed that PNCs-HCT exhibited sustained drug release similar to only PNCs but with a higher release rate than only PTX powder. Cellular uptake, cytotoxicity, and cell cycle arrest studies revealed that PNCs-HCT exhibit greater binding affinity and higher cell-specific internalization to HER2 positive breast cancer cell lines as compared to PNCs, followed by enhanced cell growth inhibition. HCT-functionalized PNCs presented in this study offer a promising strategy for targeted pure drug nanocrystal delivery and enhancing the efficiency of anticancer therapy. PMID- 27686049 TI - An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy. AB - It is important to find better treatments for diabetic nephropathy (DN), a debilitating renal complication. Targeting early features of DN, including renal extracellular matrix accumulation (ECM) and glomerular hypertrophy, can prevent disease progression. Here we show that a megacluster of nearly 40 microRNAs and their host long non-coding RNA transcript (lnc-MGC) are coordinately increased in the glomeruli of mouse models of DN, and mesangial cells treated with transforming growth factor-beta1 (TGF- beta1) or high glucose. Lnc-MGC is regulated by an endoplasmic reticulum (ER) stress-related transcription factor, CHOP. Cluster microRNAs and lnc-MGC are decreased in diabetic Chop-/- mice that showed protection from DN. Target genes of megacluster microRNAs have functions related to protein synthesis and ER stress. A chemically modified oligonucleotide targeting lnc-MGC inhibits cluster microRNAs, glomerular ECM and hypertrophy in diabetic mice. Relevance to human DN is also demonstrated. These results demonstrate the translational implications of targeting lnc-MGC for controlling DN progression. PMID- 27686051 TI - Photosensitizer-conjugated tryptophan-containing peptide ligands as new dual targeted theranostics for cancers. AB - Here we report that new dual-targeted theranostic anti-cancer agents can be produced by simple conjugation of photosensitizers with tryptophan-containing peptide ligands via cyclic disulfide linkages. In the proof-of-concept study, photosensitizers conjugated with EGFR-targeting peptide GE11 (C-EGFR) were in close proximity with tryptophan residues in the conjugate, resulting in quenching of its fluorescence and singlet oxygen generation. C-EGFR specifically binds to target receptors on the cancer cell surface, after which it is internalized via receptor-mediated endocytosis. Intracellular cleavage of cyclic disulfide bonds allows separation of the photosensitizers from the tryptophan residue, after which they emit near-infrared (NIR) fluorescence and produce a phototoxic effect in the target cells. This strategy enabled us to accomplish simultaneous real time NIR fluorescence imaging of EGFR-overexpressing cancer cells with high contrast and selective photodynamic therapy. PMID- 27686052 TI - A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices. AB - During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively. PMID- 27686053 TI - Fabrication of non-dissolving analgesic suppositories using 3D printed moulds. AB - Conventional suppositories sometimes fail in exerting their therapeutic activity as the base materials melt inside body cavities. Also they are not suitable to provide long term treatment. Biomedical grade silicone elastomers may be used to fabricate non-dissolvable suppositories to overcome these disadvantages. We kneaded 4 analgesics into the 2 kinds of silicone polymers at 1%, 5% and 10% drug loading, respectively, to test their mechanical properties and drug release profiles. The optimized drug-polymer combinations were used to fabricate suppositories, and three dimensional printing (3DP) was used to create the suppository moulds. Subsequently, the drug release profiles and biocompatibility of the suppositories were studied. It was found that, the mechanical properties of the drug laden silicone elastomers and the rate of drug release from the elastomers can be tuned by varying drug-polymer combinations. The silicone elastomers containing 1% (w/w) and 5% (w/w) diclofenac sodium were the optimal formulations with prolonged drug release and biocompatibility at cellular level. These properties, together with complex geometries offered by 3DP technique, potentially made the non-dissolving suppositories promising therapeutic agents for personalized medicine. PMID- 27686054 TI - Immunometabolic circuits in trained immunity. AB - The classical view that only adaptive immunity can build immunological memory has recently been challenged. Both in organisms lacking adaptive immunity as well as in mammals, the innate immune system can adapt to mount an increased resistance to reinfection, a de facto innate immune memory termed trained immunity. Recent studies have revealed that rewiring of cellular metabolism induced by different immunological signals is a crucial step for determining the epigenetic changes underlying trained immunity. Processes such as a shift of glucose metabolism from oxidative phosphorylation to aerobic glycolysis, increased glutamine metabolism and cholesterol synthesis, play a crucial role in these processes. The discovery of trained immunity opens the door for the design of novel generations of vaccines, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. PMID- 27686055 TI - Analyses of optimal body mass index for infertile patients with either polycystic or non-polycystic ovary syndrome during assisted reproductive treatment in China. AB - We observed the effect of body mass index (BMI) on pregnancy outcomes in Chinese patients undergoing assisted reproductive treatment (ART). All the patients were divided into polycystic ovary syndrome (PCOS) group and non-PCOS group, and then according to BMI, each group was subdivided into 6 subgroups: group 1 (BMI < 18 kg/m2), group 2 (18-20 kg/m2), group 3 (20-22 kg/m2), group 4 (22-24 kg/m2), group 5 (24-26 kg/m2) and group 6 (BMI > 26.0 kg/m2). We found that in 20 to 25 year-old patients, the pregnancy rate was not significantly correlated with BMI in PCOS patients; while in non-POCS patients, the pregnancy rate significantly decreased at the BMI cut-off point value of 24-26 kg/m2. The pregnancy rate significantly declined at the BMI cut-off point values of 22-24 kg/m2 and 18-20 kg/m2, respectively in 25 to 35-year-old and in over 35-year-old PCOS patients; while in over 25-year-old non-PCOS patients, no significant correlation between pregnancy rate and BMI was observed. We conclude that for under 25-year-old non PCOS patients, ART should be performed after BMI is controlled under 26 kg/m2. For PCOS patients, if age is 25 to 35 years or over 35 years, BMI should be controlled below 24 kg/m2 or below 20 kg/m2, respectively. PMID- 27686056 TI - Material gain engineering in GeSn/Ge quantum wells integrated with an Si platform. AB - It is shown that compressively strained Ge1-xSnx/Ge quantum wells (QWs) grown on a Ge substrate with 0.1 <= x <= 0.2 and width of 8 nm <= d <= 14 nm are a very promising gain medium for lasers integrated with an Si platform. Such QWs are type-I QWs with a direct bandgap and positive transverse electric mode of material gain, i.e. the modal gain. The electronic band structure near the center of Brillouin zone has been calculated for various Ge1-xSnx/Ge QWs with use of the 8-band kp Hamiltonian. To calculate the material gain for these QWs, occupation of the L valley in Ge barriers has been taken into account. It is clearly shown that this occupation has a lot of influence on the material gain in the QWs with low Sn concentrations (Sn < 15%) and is less important for QWs with larger Sn concentration (Sn > 15%). However, for QWs with Sn > 20% the critical thickness of a GeSn layer deposited on a Ge substrate starts to play an important role. Reduction in the QW width shifts up the ground electron subband in the QW and increases occupation of the L valley in the barriers instead of the Gamma valley in the QW region. PMID- 27686057 TI - Editorial Comment to Use of sigmoid colon in orthotopic neobladder reconstruction: Long-term results. PMID- 27686058 TI - Potential role of gene-environment interactions in ion transport mechanisms in the etiology of renal cell cancer. AB - We investigated the ion transport mechanism (ITM) in renal cell cancer (RCC) etiology using gene-environment interactions between candidate single nucleotide polymorphisms (SNPs) and associated environmental factors, including dietary intakes of sodium, potassium and fluid, hypertension and diuretic medication. A literature-based selection of 13 SNPs in ten ITM genes were successfully genotyped in toenail DNA of 3,048 subcohort members and 419 RCC cases from the Netherlands Cohort Study. Diet and lifestyle were measured with baseline questionnaires. Cox regression analyses were conducted for main effects and gene environment interactions. ADD1_rs4961 was significantly associated with RCC risk, showing a Hazard Ratio (HR) of 1.24 (95% confidence intervals (CI): 1.01-1.53) for the GT + TT (versus GG) genotype. Four of 65 tested gene-environment interactions were statistically significant. Three of these interactions clustered in SLC9A3_rs4957061, including the ones with fluid and potassium intake, and diuretic medication. For fluid intake, the RCC risk was significantly lower for high versus low intake in participants with the CC genotype (HR(95% CI): 0.47(0.26-0.86)), but not for the CT + TT genotype (P-interaction = 0.002). None of the main genetic effects and gene-environment interactions remained significant after adjustment for multiple testing. Data do not support the general hypothesis that the ITM is a disease mechanism in RCC etiology. PMID- 27686060 TI - Interspecific sensitivity of bees towards dimethoate and implications for environmental risk assessment. AB - Wild and domesticated bee species are exposed to a variety of pesticides which may drive pollinator decline. Due to wild bee sensitivity data shortage, it is unclear if the honey bee Apis mellifera is a suitable surrogate species in the current EU risk assessment scheme. Furthermore, the underlying causes for sensitivity differences in bees are not established. We assessed the acute toxicity (median lethal dose, LD50) of dimethoate towards multiple bee species, generated a species sensitivity distribution and derived a hazardous dose (HD5). Furthermore, we performed a regression analysis with body weight and dimethoate toxicity. HD5 lower 95% confidence limit was equal to honey bee mean LD50 when applying a safety factor of 10. Body weight proved to be a predictor of interspecific bee sensitivity but did not explain the pattern completely. Using acute toxicity values from honey bees and a safety factor of 10 seems to cover the interspecific sensitivity range of bees in the case of dimethoate. Acute endpoints of proposed additional test species, the buff-tailed bumblebee Bombus terrestris and the red mason bee Osmia bicornis, do not improve the risk assessment for the entire group. However, this might not apply to other insecticides such as neonicotinoids. PMID- 27686059 TI - A randomised controlled trial evaluating renal protective effects of selenium with vitamins A, C, E, verapamil, and losartan against extracorporeal shockwave lithotripsy-induced renal injury. AB - OBJECTIVE: To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy (ESWL)-induced renal injury. PATIENTS AND METHODS: A randomised controlled trial was conducted between August 2012 and February 2015. Inclusion criteria were adult patients with a single renal stone (<2 cm) suitable for ESWL. Patients with diabetes, hypertension, congenital renal anomalies, moderate or marked hydronephrosis, or preoperative albuminuria (>300 mg/L) were excluded. ESWL was performed using the electromagnetic DoLiS lithotripter. Eligible patients were randomised into one of four groups using sealed closed envelopes: Group1, control; Group 2, selenium ACE; Group 3, losartan; and Group 4, verapamil. Albuminuria and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were estimated after 2-4 h and 1 week after ESWL. The primary outcome was differences between albuminuria and uNGAL. Dynamic contrast-enhanced magnetic resonance imaging was performed before ESWL, and at 2-4 h and 1 week after ESWL to compare changes in renal perfusion. RESULTS: Of 329 patients assessed for eligibility, the final analysis comprised 160 patients (40 in each group). Losartan was the only medication that showed significantly lower levels of albuminuria after 1 week (P < 0.001). For perfusion changes, there was a statistically significant decrease in the renal perfusion in patients with obstructed kidneys in comparison to before ESWL (P = 0.003). These significant changes were present in the control or antioxidant group, whilst in the losartan and verapamil groups renal perfusion was not significantly decreased. CONCLUSIONS: Losartan was found to protect the kidney against ESWL-induced renal injury by significantly decreasing post-ESWL albuminuria. Verapamil and losartan maintained renal perfusion in patients with post-ESWL renal obstruction. PMID- 27686061 TI - Electrospun nanofibres to mimic natural hierarchical structure of tissues: application in musculoskeletal regeneration. AB - Biomimetic scaffolds mimicking the natural hierarchical structure of tissues have recently attracted the interest of researchers and provide a promising strategy to resemble the nonhomogeneous property of tissues. This review provides an overview of the various hierarchical length scales in the native tissues of the musculoskeletal system. It further focuses on electrospinning as a technique to mimic the tissue structures with specific emphasis on bone. The effect of cellular alignment, infiltration, vascularisation, and differentiation in these nanostructures has also been discussed. An outline of the various additive manufacturing techniques in combination with electrospinning has been elaborated. The review concludes with the challenges and future directions to understand the intricacies of bottom-up approach to engineer the systems at a macroscale. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27686062 TI - Do Circadian Rhythms Draw the Patterns of Sustained Mental Vigor and Ailment? AB - Preclinical Research Circadian rhythms are fundamental processes in all cells that coordinate a variety of cellular functions related to a specific time of the day. Disruption of circadian rhythms markedly impacts homeostasis. In this Commentary, we present data that disruption of circadian rhythm may lead to the pathogenesis of neurodegenerative states. In this context, we further argue that there is an urgent need of developing new generations of compounds, chronobiotics, to modulate the molecular substrates of circadian timing system. Chronobiotics conceptually offer an effective way for restoration and protection from the consequences of the circadian disruption. We also briefly discuss whether dysfunctional circadian rhythms are a major driver of aging. Drug Dev Res 77 : 469-473, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27686063 TI - The effect of select seminal plasma proteins on endometrial mRNA cytokine expression in mares susceptible to persistent mating-induced endometritis. AB - In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating-induced endometritis PMIE Select seminal plasma proteins cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP-3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ml CRISP-3, 150 MUg/ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 * 109 spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro-inflammatory cytokines interleukin (IL)-1beta, IL-8, tumour necrosis factor (TNF)-alpha, interferon (INF)-gamma, anti-inflammatory cytokines IL-1RN and IL-10, and inflammatory-modulating cytokine IL-6). Seminal plasma treatment increased the mRNA expression of IL-1beta (p = .019) and IL-8 (p = .0068), while suppressing the mRNA expression of TNF (p = .0013). Lactoferrin also suppressed the mRNA expression of TNF (p = .0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro-inflammatory response seen in susceptible mares. PMID- 27686064 TI - May cannabinoids prevent the development of chemotherapy-induced diarrhea and intestinal mucositis? Experimental study in the rat. AB - BACKGROUND: The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat. METHODS: Male Wistar rats received vehicle or the non-selective cannabinoid agonist WIN 55,212-2 (WIN; 0.5 mg kg-1 injection 1 , 1 injection day-1 , 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5-FU (150 mg kg-1 injection-1 , cumulative dose of 300 mg kg-1 ). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. KEY RESULTS: As shown radiographically, 5-FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5-FU treated animals but tended to reduce the severity of 5-FU-induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5-FU treated animals. 5-FU-induced mucositis was severe and not counteracted by WIN. CONCLUSIONS AND INFERENCES: 5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy-induced diarrhea. PMID- 27686065 TI - A non-targeted metabolite profiling pilot study suggests that tryptophan and lipid metabolisms are linked with ADHD-like behaviours in dogs. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent and multifactorial neuropsychiatric disorder in the human population worldwide. Complex etiology and clinical heterogeneity have challenged the research, diagnostics and treatment of the disease. Hyperactive and impulsive behaviour has also been observed in dogs, and they could offer a physiologically relevant model for human ADHD. As a part of our ongoing study to understand the molecular etiology of canine anxiety traits, this study was aimed to pilot an approach to identify metabolic biomarkers in canine ADHD-like behaviours for research, diagnostics and treatment purposes. METHODS: We collected fresh plasma samples from 22 German Shepherds with varying ADHD-like behaviours. All dogs were on the same controlled diet for 2 weeks prior to sampling. A liquid chromatography combined with mass spectrometry (LC-MS)-based non-targeted metabolite profiling was performed to identify plasma metabolites correlating with the ADHD-like behaviour of the dogs. RESULTS: 649 molecular features correlated with ADHD-like behavioural scores (praw < 0.05), and three of them [sn-1 LysoPC(18:3), PC(18:3/18:2) and sn-1 LysoPE(18:2)] had significant correlations also after FDR correction (pFDR < 0.05). Phospholipids were found to negatively correlate with ADHD-like behavioural scores, whereas tryptophan metabolites 3-indolepropionic acid (IPA) and kynurenic acid (KYNA) had negative and positive correlations with ADHD-like behavioural scores, respectively. CONCLUSIONS: Our study identified associations between canine ADHD-like behaviours and metabolites that are involved in lipid and tryptophan metabolisms. The identified metabolites share similarity with earlier findings in human and rodent ADHD models. However, a larger replication study is warranted to validate the discoveries prior to further studies to understand the biological role of the identified metabolites in canine ADHD-like behaviours. PMID- 27686066 TI - Mortality and treatment costs of hospitalized chronic kidney disease patients between the three major health insurance schemes in Thailand. AB - BACKGROUND: Thailand has reformed its healthcare to ensure fairness and universality. Previous reports comparing the fairness among the 3 main healthcare schemes, including the Universal Coverage Scheme (UCS), the Civil Servant Medical Benefit Scheme (CSMBS) and the Social Health Insurance (SHI) have been published. They focused mainly on provision of medication for cancers and human immunodeficiency virus infection. Since chronic kidney disease (CKD) patients have a high rate of hospitalization and high risk of death, they also require special care and need more than access to medicine. We, therefore, performed a 1 year, nationwide, evaluation on the clinical outcomes (i.e., mortality rates and complication rates) and treatment costs for hospitalized CKD patients across the 3 main health insurance schemes. METHODS: All adult in-patient CKD medical expense forms in fiscal 2010 were analyzed. The outcomes focused on were clinical outcomes, access to special care and equipment (especially dialysis), and expenses on CKD patients. Factors influencing mortality rates were evaluated by multiple logistic regression. RESULTS: There were 128,338 CKD patients, accounting for 236,439 admissions. The CSMBS group was older on average, had the most severe co-morbidities, and had the highest hospital charges, while the UCS group had the highest rate of complications. The mortality rates differed among the 3 insurance schemes; the crude odds ratio (OR) for mortality was highest in the CSMBS scheme. After adjustment for biological, economic, and geographic variables, the UCS group had the highest risk of in-hospital death (OR 1.13;95 % confidence interval (CI) 1.07-1.20; p < 0.001) while the SHI group had lowest mortality (OR 0.87; 95 % CI 0.76-0.99; p = 0.038). The circumscribed healthcare benefits and limited access to specialists and dialysis care in the UCS may account for less favorable comparison with the CSMBS and SHI groups. CONCLUSIONS: Significant differences are observed in mortality rates among CKD patients from among the 3 main healthcare schemes. Improvements in equity of care might minimize the differences. PMID- 27686067 TI - What are the barriers to access to mental healthcare and the primary needs of asylum seekers? A survey of mental health caregivers and primary care workers. AB - BACKGROUND: We aimed to assess the opinion of primary care workers, social workers, translators and mental health caregivers who work with asylum seekers about the latter's unmet needs and barriers to access to mental healthcare. METHODS: We used a Likert scale to assess the opinion of 135 primary care workers (general practitioners, nurses, social workers and translators) and mental health caregivers about the proportion of asylum seekers with psychiatric disorders, their priority needs and their main barriers to mental health services. RESULTS: Insufficient access to adequate financial resources, poor housing and security conditions, access to employment, professional training and legal aid were considered as priority needs, as were access to dental and mental healthcare. The main barriers to access to mental healthcare for asylum seekers included a negative representation of psychiatry, fear of being stigmatized by their own community and poor information about existing psychiatric services. CONCLUSIONS: We found a good correlation between the needs reported by healthcare providers and those expressed by the asylum-seeking population in different studies. We discuss the need for greater mobility and accessibility to psychiatric services among this population. PMID- 27686068 TI - Functional analysis of PrkA - a putative serine protein kinase from Mesorhizobium alhagi CCNWXJ12-2 - in stress resistance. AB - BACKGROUND: Serine/threonine protein kinases are highly conserved kinases with a wide distribution in microbes and with multiple functions. Mesorhizobium alhagi CCNWXJ12-2, a alpha-proteobacterium which could be able to form symbiosis with Alhagi sparsifolia in northwest of China, contains a putative PrkA-family serine protein kinase, PrkA. In our previous study, the expression of prkA was found to be downregulated in high-salt conditions. To elucidate the function of M. alhagi PrkA, a prkA deletion mutant was constructed and the phenotypes of the mutant were analyzed. RESULTS: The salt and alkaline tolerance and antioxidant capacity of the wild-type strain and the prkA deletion mutant was measured. Our results showed that the deletion mutant had higher salt and alkaline tolerance than the wild-type strain. The total cellular Na+ content was measured and showed no significant difference between the wild-type strain and the mutant. The prkA deletion mutant also showed a higher H2O2 tolerance than the wild-type strain. Therefore the activities of antioxidant enzymes were measured. Catalase activity was similar in the wild-type and the deletion mutant, while the superoxide dismutase activity in the mutant was higher than that in the wild-type. CONCLUSIONS: We firstly analyze the function of a serine protein kinase, PrkA, in M. alhagi. Our data indicate that PrkA could reduce the survival of M. alhagi under environmental stress and deletion of prkA dramatically improved the salt and alkaline tolerance and antioxidant capacity of M. alhagi. PMID- 27686070 TI - Analysis of the complete genome sequence of euphorbia ringspot virus, an atypical member of the genus Potyvirus. AB - The complete genome sequence of an isolate of euphorbia ringspot virus (EuRSV) was determined by deep sequencing and rapid amplification of cDNA ends (RACE) RT PCR. It has an RNA genome of 10,154 nucleotides in size, excluding the poly(A) tail, and encodes a polyprotein of 3265 amino acids. Phylogenetic analysis from this study supports the earlier taxonomic assignment to the genus Potyvirus; however, a gene encoding the HAM1h protein, inserted between NIb and CP of the EuRSV genome, which was previously only observed for cassava brown streak virus and Ugandan cassava brown streak virus of the genus Ipomovirus, is an unusual feature of this potyvirus, which otherwise has typical potyvirus genome features. PMID- 27686069 TI - Developmental piRNA profiles of the invasive vector mosquito Aedes albopictus. AB - BACKGROUND: In eukaryotic organisms, Piwi-interacting RNAs (piRNAs) control the activities of mobile genetic elements and ensure genome maintenance. Recent evidence indicates that piRNAs are involved in multiple biological pathways, including transcriptional regulation of protein-coding genes, sex determination and even interactions between host and pathogens. Aedes albopictus is a major invasive species that transmits a number of viral diseases in humans. Ae. albopictus has the largest genome and the highest abundance of repetitive sequences when compared with members that belong to Culicidae with a published genome. Analysis of piRNA profiles will provide a developmental and evolutionary perspective on piRNAs in Ae. albopictus. METHODS: piRNAs were identified and characterized during the development of Ae. albopictus, and piRNA expression patterns in adult males and females as well as sugar-fed females and blood-fed females were compared. RESULTS: Our results reveal that, despite the large genome size of Ae. albopictus, the piRNA pool of Ae. albopictus (1.2 * 107) is smaller than those of Aedes aegypti (1.7 * 107) and Drosophila melanogaster (1.6 * 107). In Ae. albopictus, piRNAs displayed the highest abundance at the embryo stage and the lowest abundance at the pupal stage. Approximately 50 % of the piRNAs mapped to intergenic regions with no known functions. Approximately 30 % of the piRNAs mapped to repetitive elements, and 77.69 % of these repeat-derived piRNAs mapped to Class I TEs; 45.42 % of the observed piRNA reads originated from piRNA clusters, and most of the top 10 highest expressed piRNA clusters and 100 highest expressed piRNAs from each stage displayed biased expression patterns across the developmental stages. All anti-sense-derived piRNAs displayed a preference for uridine at the 5' end; however, the sense-derived piRNAs showed adenine bias at the tenth nucleotide position and a typical ping-pong signature, suggesting that the biogenesis of piRNAs was conserved throughout development. Our results also show that 962 piRNAs displayed sex-biased expression, and 522 piRNAs showed higher expression in the blood-fed females than in the sugar-fed females. CONCLUSIONS: Our results suggest that piRNAs, aside from silencing transposable elements in Ae. albopictus, may have a role in other biological pathways. PMID- 27686072 TI - Susceptibility of chickens, quail, and pigeons to an H7N9 human influenza virus and subsequent egg-passaged strains. AB - H7N9 human influenza virus A/Anhui/1/2013 (Anhui2013) showed low pathogenicity in chickens, quail, and pigeons, with quail being the most susceptible among the species tested. IVPIE1-1, which was recovered from a dead chicken after intravenous inoculation of Anhui 2013, had broader tissue tropism in chickens than did the original inoculum, as well as amino acid substitutions in the polymerase acidic gene and neuraminidase gene segments, but its pathogenicity was not enhanced. Viruses obtained after passage of Anhui 2013 in 10- and 14-day-old embryonated eggs showed rapid accumulation of amino acid substitutions at the receptor-binding site of the hemagglutinin protein. Two strains obtained through egg passage, 10E4/14E17 and 10E4/10E13, replicated better in intranasally infected chickens than did the original Anhui 2013 strain, yet the new isolates showed low pathogenicity in chickens despite their amino acid substitutions. The increased virus replication in chickens of 10E4/14E17 and 10E4/10E13 was not correlated with temperature-sensitive replication, given that virus replication was suppressed at increased temperatures. The existence of highly susceptible hosts, such as quail, which permit asymptomatic infection, facilitates increased mutation of the virus through amino acid substitution at the receptor-binding site, and this might be one of the mechanisms underlying the prolonged circulation of H7N9 influenza virus. PMID- 27686071 TI - Expression patterns of endogenous avian retrovirus ALVE1 and its response to infection with exogenous avian tumour viruses. AB - Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates and have been implicated in a variety of human diseases, including cancer. However, the characteristic expression patterns of ERVs, particularly in virus-induced tumours, is not fully clear. DNA methylation was analysed by bisulfite pyrosequencing, and gene expression was analysed by RT qPCR. In this study, we first found that the endogenous avian retrovirus ALVE1 was highly expressed in some chicken tissues (including the heart, bursa, thymus, and spleen) at 2 days of age, but its expression was markedly decreased at 35 days of age. In contrast, the CpG methylation level of ALVE1 was significantly lower in heart and bursa at 2 days than at 35 days of age. Moreover, we found that the expression of ALVE1 was significantly inhibited in chicken embryo fibroblast cells (CEFs) and MSB1 cells infected with avian leukosis virus subgroup J (ALVJ) and reticuloendotheliosis virus (REV) at the early stages of infection. In contrast, the expression of the ALVE1 env gene was significantly induced in CEFs and MSB1 cells infected with Marek's disease virus (MDV). However, the methylation and expression levels of the ALVE1 long terminal repeat (LTR) did not show obvious alterations in response to viral infection. The present study revealed the expression patterns of ALVE1 in a variety of chicken organs and tissues and in chicken cells in response to avian tumour virus infection. These findings may be of significance for understanding the role and function of ERVs that are present in the host genome. PMID- 27686073 TI - The prevalence of enteric RNA viruses in stools from diarrheic and non-diarrheic people in southwestern Alberta, Canada. AB - Southwestern Alberta is a region of Canada that has high rates of enteritis as well as high densities of livestock. The presence of enteric RNA viruses, specifically norovirus (NoV) GI, GII, GIII, GIV; sapovirus (SaV); rotavirus (RV); and astrovirus (AstV), was evaluated in stools from diarrheic (n = 2281) and non diarrheic (n = 173) people over a 1-year period in 2008 and 2009. Diarrheic individuals lived in rural (46.6 %) and urban (53.4 %) settings and ranged in age from less than 1 month to 102 years, and the highest prevalence of infection in these individuals was in November. In all, viruses were detected in diarrheic stools from 388 individuals (17.0 %). NoV GII was the most frequently detected virus (8.0 %; n = 182) followed by SaV (4.3 %; n = 97), RV (2.0 %; n = 46), AstV (1.8 %; n = 42), NoV GI (0.9 %; n = 20), and NoV GIV (0.1 %; n = 1). Animal NoV GIII was never detected. The prevalence of mixed viral infections in diarrheic individuals was 2.8 % (n = 11). Children from 1 to 5 years of age accounted for the highest prevalence of positive stools, followed by the elderly individuals (>=70 years). Only NoV GII (1.2 %; n = 2) and SaV (1.2 %; n = 2) were detected in stools from non-diarrheic people. Sequence analysis of a subset of stools revealed homology to NoV, SaV and RV sequences from humans but not to strains from non-human animals. The results of this study do not support the hypothesis that viruses of animal origin have a significant impact on the occurrence of acute gastroenteritis caused by RNA enteric viruses in people living in southwestern Alberta. PMID- 27686074 TI - Molecular detection of enteric viruses from diarrheic calves in Egypt. AB - Neonatal calf diarrhea (NCD) is a major cause of morbidity, mortality and economic losses in the beef and dairy industries. This study was conducted to investigate the existence of enteric viruses in two Egyptian farms with a history of recurrent diarrhea. Fecal samples were collected from 25 diarrheic calves. RNA was extracted and tested by reverse transcription polymerase chain reaction (RT PCR) for the presence of rotavirus, norovirus, astrovirus, torovirus, coronavirus and bovine viral diarrhea virus. Overall, 76 % (19/25) of samples tested positive for one or more viruses. Rota-, noro- and astroviruses were detected in 48 %, 24 % and 32 % of tested samples, respectively. About 37 % (7/19) of positive samples had two different viruses. One-month-old calves were the group most vulnerable to infections. Based on phylogenetic analysis, bovine rotaviruses were of genotypes G6 and G10, bovine noroviruses were in GIII.2, and bovine astroviruses were in the BAstV lineage 1. Astrovirus sequences showed a high level nucleotide sequence similarity with the Brazilian BAstV sequences available in GenBank. We believe this is the first report of bovine norovirus and bovine astrovirus circulating among calves in Egypt. Further epidemiological studies are recommended to investigate their presence on a wider scale, to predict their association with NCD, and to design appropriate diagnostic and control methods. PMID- 27686075 TI - Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia. AB - Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n = 15), BCCAO control group (n = 15), and BV-treated BCCAO group (n = 15). BCCAO animals were treated with 0.1 MUg/g BV at ST36 ("Joksamli" acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-alpha. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia. PMID- 27686076 TI - Carnosic Acid Protects Mitochondria of Human Neuroblastoma SH-SY5Y Cells Exposed to Paraquat Through Activation of the Nrf2/HO-1Axis. AB - Carnosic acid (CA; C20H28O4), which is also called salvin, is a major phenolic diterpene found in Rosmarinus officinalis L. and exhibits antioxidant, anti inflammatory, and antiproliferative properties. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, leading to the upregulation of antioxidant and phase II detoxification enzymes, such as heme oxygenase-1 (HO-1), glutathione reductase (GR), gamma-glutamate-cysteine ligase (gamma-GCL), and glutathione S-transferase (GST), among others. We have previously demonstrated that CA upregulates the total and mitochondrial synthesis of glutathione (GSH), causing mitochondrial protection against paraquat (PQ) and methylglyoxal (MG). Nonetheless, the complete mechanism by which CA prevented mitochondrial dysfunction was not clear yet. Here, we examine whether HO-1 would be involved in the CA-induced mechanism of mitochondrial protection in SH-SY5Y treated cells. SH-SY5Y cells were pretreated with CA (1 MUM) for 12 h prior to a challenge with PQ at 100 MUM for additional 24 h. Zinc protoporphyrin IX (ZnPP IX; a specific inhibitor of HO-1; 10 MUM) was utilized prior to exposure to CA in order to investigate whether HO-1 was involved in the cytoprotective effects elicited by CA. We found that the CA-induced Nrf2-dependent HO-1 upregulation ameliorated, at least in part, the mitochondrial function in PQ-treated cells. Therefore, CA protected mitochondria of SH-SY5Y cells and exerted anti-apoptotic effects by activating the Nrf2/HO-1 axis. PMID- 27686077 TI - PPAR-alpha Modulates the Anti-Inflammatory Effect of Melatonin in the Secondary Events of Spinal Cord Injury. AB - Melatonin is the principal secretory product of the pineal gland, and its role as an immunomodulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and reduces the development of inflammation and tissue injury events associated with spinal cord trauma. Previous results suggest that peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear receptor protein that functions as a transcription factor activated by fatty acids, plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI).With the aim to characterize the role of PPAR-alpha in melatonin-mediated anti-inflammatory activity, we tested the efficacy of melatonin (30 mg/kg) in an experimental model of spinal cord trauma, induced in mice, by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR alpha (PPAR-alpha KO) with wild-type (WT) mice.The results obtained indicate that melatonin-mediated anti-inflammatory activity is weakened in PPAR-alpha KO mice, as compared to WT controls. In particular, melatonin was less effective in PPAR alpha KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, pro-inflammatory cytokine expression, nuclear factor kappaB (NF-kappaB) activation, and inducible nitric oxide synthase (iNOS) expression. This study indicates that PPAR-alpha can contribute to the anti-inflammatory activity of melatonin in SCI. PMID- 27686079 TI - Pas de Deux. AB - In this personal essay, Mark Osteen uses the metaphor of a pas de deux to dramatize how caring for his autistic son has enriched his scholarship and teaching. In his early years as the father of an autistic child, Osteen's parental and professional roles clashed, but gradually he learns to use what his son teaches him-particularly about nonverbal communication and multiple forms of intelligence-to develop a theory of empathetic scholarship and to enhance his pedagogy. PMID- 27686078 TI - Association of ACYP2 and TSPYL6 Genetic Polymorphisms with Risk of Ischemic Stroke in Han Chinese Population. AB - The development of ischemic stroke is associated with advanced age. Telomere length, as a marker of biological aging, has been reported to influence the risk of several age-related diseases, including ischemic stroke. Recent studies have identified the genetic variant within ACYP2 and TSPYL6 associated with shorter telomere length. The objective of this study is to investigate the putative association of ischemic stroke with common polymorphisms in ACYP2 and TSPYL6 genes in a Chinese Han population. We found that the risk alleles of six single nucleotide polymorphisms (SNPs), including rs11125529, rs12615793, rs843711, rs11896604, and rs843706 within both ACYP2 and TSPYL6, and rs17045754 in ACYP2 gene, were related with increased risk of ischemic stroke according to both allelic and genotype association analyses. The significant correlations between ACYP2 and TSPYL6 SNPs and ischemic stroke risk were also observed in dominant, recessive, and additive models, respectively. Two blocks in high linkage disequilibrium were identified in this study, and two haplotypes were associated with higher ischemic stroke susceptibility. In conclusion, the genetic polymorphisms of ACYP2 and TSPYL6 are associated with increased risk of developing ischemic stroke. Further studies with larger sample sizes are required to validate our findings. PMID- 27686081 TI - [Back to the Future. Vaccine trials against Ebola in the history of resistance to immunization]. AB - Vaccine trials against Ebola virus have been conceived and organized, in August 2014, after the epidemic started in three countries of West Africa. If the preparedness had been missing, the planners tried to anticipate the resistance to vaccination, in Guinea, Sierra Leone and Liberia. This article offers a retrospective view on the resistances to vaccination throughout its history, from smallpox inoculation to anti-polio vaccine. Resistances have been linked to the political contexts and the rejection of an oppressive power, either local or foreign, as well as mistakes and scientific uncertainties. The analysis of the historical factors of resistance leads to reverse the question: what convinces people to accept a vaccine trial, despite the obscurities of the immunization processes inside the body? The article hypothesizes that Guineans and West Africans face a dilemma similar to their counterparts in the past, whether or not to rally to an experimental immunization, the results of which are still pending. They may appropriate the Western beliefs about the efficacy of vaccines to their own ways of circumventing misfortune. Further field studies will be required to assess the role of the vaccinal trials and the response to the epidemic in the "convalescence" of these societies, being aware that the trials will not allow a complete assessment of the vaccines, because of the end of the epidemic. PMID- 27686082 TI - Re: Prognostic value of CALR vs. JAK2V617F mutations on splenomegaly, leukemic transformation, thrombosis, and overall survival in patients with primary fibrosis: a meta-analysis. PMID- 27686080 TI - Metal Nanomaterial Toxicity Variations Within the Vascular System. AB - Engineered nanomaterials (ENM) are anthropogenic materials with at least one dimension less than 100 nm. Their ubiquitous employment in biomedical and industrial applications in the absence of full toxicological assessments raises significant concerns over their safety on human health. This is a significant concern, especially for metal and metal oxide ENM as they may possess the greatest potential to impair human health. A large body of literature has developed that reflects adverse systemic effects associated with exposure to these materials, but an integrated mechanistic framework for how ENM exposure influences morbidity remains elusive. This may be due in large part to the tremendous diversity of existing ENM and the rate at which novel ENM are produced. In this review, the influence of specific ENM physicochemical characteristics and hemodynamic factors on cardiovascular toxicity is discussed. Additionally, the toxicity of metallic and metal oxide ENM is presented in the context of the cardiovascular system and its discrete anatomical and functional components. Finally, future directions and understudied topics are presented. While it is clear that the nanotechnology boom has increased our interest in ENM toxicity, it is also evident that the field of cardiovascular nanotoxicology remains in its infancy and continued, expansive research is necessary in order to determine the mechanisms via which ENM exposure contributes to cardiovascular morbidity. PMID- 27686083 TI - Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion. AB - Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia. PMID- 27686084 TI - Markers of endothelial dysfunction and leucocyte activation in Saudi and non Saudi haplotypes of sickle cell disease. AB - Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling. Studies are underway to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCD patients. PMID- 27686085 TI - Endothelial progenitor cells improve the quality of transplanted hematopoietic stem cells and maintain longer term effects in mice. AB - Engraftment of hematopoietic stem cells (HSCs) is a pre-requisite for the success of hematopoietic stem cell transplantation (HSCT). Fetal blood cell (FBC)-derived endothelial progenitor cells (EPCs) are known to facilitate HSC reconstitution in the early phase. However, longer term effects on HSCs remain unclear. The purpose of this study was to evaluate the effect of EPCs on the quality of transplanted hematopoietic stem cells in mouse HSCT model. BALB/c mice were randomly divided into four groups, namely, control, total body irradiation only, HSCT, and HSCT + EPCs (with infusion of 5 * 105 EPCs). Mice was sacrificed on days 7, 14, 21, and 28 post-HSCT for the analysis of the bone marrow pathology by H&E staining, measurement of c-kit+sca-1+, c-kit+, apoptosis, and necrosis by flow cytometry as well as colony formation assay. Secondary transplantation involved the injection of transplanted BALB/c-derived HSCs into new TBI-treated BALB/c mice. Compared with HSCT, EPCs infusion promoted the differentiation and reduced apoptosis of transplanted HSCs, possibly through promotion of vascular repair of the bone marrow microenvironment via differentiation into the bone marrow endothelial cells. Significantly, EPCs' effect on HSCs was maintained for a long period as demonstrated using a secondary transplantation approach. These data revealed EPCs improved the quality and quantity of transplanted HSCs and maintained their effects over the longer term, suggesting a novel approach to improve HSCT efficiency and outcomes. PMID- 27686086 TI - Radiological findings and radiation exposure during trauma workup in a cohort of 1124 level 1 trauma patients. AB - BACKGROUND: During the initial assessment of patients with potential severe injuries, radiological examinations are performed in order to rapidly diagnose clinically relevant injuries. Previous studies have shown that performing these examinations routinely is not always necessary and that trauma patients are exposed to substantial radiation doses. The aim of this study was to assess the amount and findings of radiological examinations during the initial assessment of trauma patients and to determine the radiation doses to which these patients are exposed to. METHODS: We analyzed the 1124 patients included in a randomized trial. All radiological examinations during the initial assessment (i.e., primary and secondary survey) were assessed. The examination results were categorized as positive findings (i.e., (suspicion for) traumatic injury) and normal findings. The effective radiation doses for the examinations were calculated separately for each patient. RESULTS: Eight hundred and three patients were male (71 %), median age was 38 years, and 1079 patients sustained blunt trauma (96 %). During initial assessment, almost 3900 X-rays were performed, of which 25.4 % showed positive findings. FAST of the abdomen was performed in 989 patients (88 %), with positive findings in 10.6 %. Additional CT scanning of specific body regions was performed 1890 times in 813 patients (72.1 %), of which approximately 43.4 % revealed positive findings. Hemodynamically stable patients showed more normal findings on the radiographic studies than unstable patients. The mean radiation doses for the total population was 8.46 mSv (+/-7.7) and for polytraumatized patients (ISS >= 16) 14.3 mSv (+/-9.5). CONCLUSION: Radiological diagnostics during initial assessment of trauma patients show a high rate of normal findings in our trauma system. The radiation doses to which trauma patients are exposed are considerable. Considering that the majority of the injured patients are hemodynamically stable, we suggest more selective use of X-ray and CT scanning. PMID- 27686090 TI - Alcohol consumption in Europe is still cause for alarm despite decrease, says WHO. PMID- 27686088 TI - Introduction to the Special Section on Culture and Variants of Sex/Gender: Bias and Stigma. AB - As a side effect of globalization, the ideological and religious heterogeneity of many local populations is increasing. This trend is particularly noticeable at tertiary-care medical centers serving patients with rare conditions such as somatic intersexuality or gender dysphoria and transgenderism (both with and without somatic intersexuality). This special section is designed to familiarize clinicians and researchers with culture-associated gender bias and stigma that may influence attitudes to individuals with somatic or behavioral gender atypicalities. PMID- 27686087 TI - Influence of Three Citrus Herbicides on Potential Production of Sorghum bicolor 'Topper 76-6' as a Bioenergy Crop. AB - Planting bioenergy crops on land previously used for citrus production may offer an alternative source of revenue for growers looking for alternative-to-citrus crops. However, residual herbicides used in citrus production may adversely affect alternative crops. This study evaluated effects of three herbicides (bromacil, norflurazon, and simazine) commonly used in citrus production on the bioenergy crop Sorghum bicolor 'Topper 76-6'. Plants were exposed to herbicides in soil for 1-5 weeks and observations of effects on photosynthetic quantum yield, leaf greenness, height, and biomass were made. Results indicate that concentrations of bromacil and norflurazon greater than 0.09 and 0.07 mg/kg and simazine >0.46 mg/kg will impair growth and development in similar soils. Concentrations below these may also be toxic. PMID- 27686089 TI - The Diversity and Prevalence of Sexual Orientation Self-Labels in a New Zealand National Sample. AB - In this study, we asked participants to "describe their sexual orientation" in an open-ended measure of self-generated sexual orientation. The question was included as part of the New Zealand Attitudes and Values Study (N = 18,261) 2013/2014 wave, a national probability survey conducted shortly after the first legal same-sex marriages in New Zealand. We present a two-level classification scheme to address questions about the prevalence of, and demographic differences between, sexual orientations. At the most detailed level of the coding scheme, 49 unique categories were generated by participant responses. Of those who responded with the following, significantly more were women: bisexual (2.1 % of women, compared to 1.5 % of men), bicurious (0.7 % of women, 0.4 % of men), and asexual (0.4 % of women and less than 0.1 % of men). However, significantly fewer women than men reported being lesbian or gay (1.8 % of women, compared to 3.5 % of men). Those openly identifying as bicurious, bisexual, or lesbian/gay were significantly younger than those with a heterosexual orientation. This study shows diversity in the terms used in self-generated sexual orientations, and provides up-to-date gender, age, and prevalence estimates for the New Zealand population. Finally, results reveal that a substantial minority of participants may not have understood the question about sexual orientation. PMID- 27686091 TI - 4-Nitrobenzene Grafted in Porous Silicon: Application to Optical Lithography. AB - In this work, we report a method to process porous silicon to improve its chemical resistance to alkaline solution attacks based on the functionalization of the pore surface by the electrochemical reduction of 4-nitrobenzendiazonium salt. This method provides porous silicon with strong resistance to the etching solutions used in optical lithography and allows the fabrication of tailored metallic contacts on its surface. The samples were studied by chemical, electrochemical, and morphological methods. We demonstrate that the grafted samples show a resistance to harsh alkaline solution more than three orders of magnitude larger than that of pristine porous silicon, being mostly unmodified after about 40 min. The samples maintained open pores after the grafting, making them suitable for further treatments like filling by polymers. Optical lithography was performed on the functionalized samples, and electrochemical characterization results are shown. PMID- 27686092 TI - Social Maturity and Executive Function Among Deaf Learners. AB - Two experiments examined relations among social maturity, executive function, language, and cochlear implant (CI) use among deaf high school and college students. Experiment 1 revealed no differences between deaf CI users, deaf nonusers, and hearing college students in measures of social maturity. However, deaf students (both CI users and nonusers) reported significantly greater executive function (EF) difficulties in several domains, and EF was related to social maturity. Experiment 2 found that deaf CI users and nonusers in high school did not differ from each other in social maturity or EF, but individuals who relied on sign language reported significantly more immature behaviors than deaf peers who used spoken language. EF difficulties again were associated with social maturity. The present results indicate that EF and social maturity are interrelated, but those relations vary in different deaf subpopulations. As with academic achievement, CI use appears to have little long-term impact on EF or social maturity. Results are discussed in terms of their convergence with findings related to incidental learning and functioning in several domains. PMID- 27686094 TI - Gallstone mimicry: a rare cause of abdominal pain. PMID- 27686095 TI - The English Version of the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (C&A-GTS-QOL). AB - Gilles de la Tourette syndrome is a chronic neuropsychiatric disorder that can have a detrimental impact on the health-related quality of life of children with the condition. To date no patient-reported health-related quality of life measures have been developed for children and adolescents in the English language. This study validated the first disease-specific scale for the quantitative assessment of health-related quality of life in 118 children and adolescents with Gilles de la Tourette syndrome (C&A-GTS-QOL) following language adaptation from Italian to English in the United Kingdom. Standard statistical methods were used to test the psychometric properties of the rating scale. Principal component factor analyses led to the identification of six health related quality of life domains (cognitive, copro-phenomena, psychological, physical, obsessive-compulsive, and activities of daily living), explaining 66.7% of the overall variance. The C&A-GTS-QOL demonstrated satisfactory scaling assumptions and acceptability; validity was supported by interscale correlations (range 0.2-0.7), confirmatory factor analysis, and correlation patterns with other rating scales and clinical variables. PMID- 27686096 TI - Efficacy of Low-Dose Corticosteroid Therapy Versus High-Dose Corticosteroid Therapy in Bell's Palsy in Children. AB - Bell's palsy is the most common cause of acute peripheral facial nerve paralysis, but the optimal dose of corticosteroids in pediatric patients is still unclear. This retrospective study aimed to evaluate the efficacy of low-dose corticosteroid therapy compared with high-dose corticosteroid therapy in children with Bell's palsy. Patients were divided into 2 groups based on the dose of oral prednisolone regimen initiated. The severity of idiopathic facial nerve paralysis was graded according to the House-Brackmann Grading Scale. The patients were re assessed in terms of recovery rate at the first, third, and sixth months of treatment. There was no significant difference in complete recovery between the 2 groups after 1, 3, and 6 months of treatment. In our study, we concluded that even at a dose of 1 mg/kg/d, oral prednisolone was highly effective in the treatment of Bell's palsy in children. PMID- 27686093 TI - Hepatic overexpression of cAMP-responsive element modulator alpha induces a regulatory T-cell response in a murine model of chronic liver disease. AB - OBJECTIVE: Th17 cells are a subset of CD4+ T-helper cells characterised by interleukin 17 (IL-17) production, a cytokine that plays a crucial role in inflammation-associated diseases. The cyclic AMP-responsive element modulator alpha (CREMalpha) is a central mediator of T-cell pathogenesis, which contributes to increased IL-17 expression in patients with autoimmune disorders. Since an increased Th17 response is associated with a poor prognosis in patients with chronic liver injury, we investigated the relevance of Th17 cells for chronic liver disease (CLD) and hepatocarcinogenesis. DESIGN: Transgenic mice overexpressing CREMalpha were crossed with hepatocyte-specific Nemo knockout mice (NemoDeltahepa) to generate NemoDeltahepa/CREMalphaTg mice. The impact of CREMalphaTg on CLD progression was examined. Additionally, soft agar colony formation assays, in vitro studies, adoptive transfer of bone marrow-derived cells (BMDCs) and T cells, and gene arrays in T cells were performed. RESULTS: 8 week-old NemoDeltahepa/CREMalphaTg mice presented significantly decreased transaminase levels, concomitant with reduced numbers of CD11b+ dendritic cells and CD8+ T cells. CREMalphaTg overexpression in NemoDeltahepa mice was associated with significantly reduced hepatic fibrogenesis and carcinogenesis at 52 weeks. Interestingly, hepatic stellate cell-derived retinoic acid induced a regulatory T cell (Treg) phenotype in CREMalphaTg hepatic T cells. Moreover, simultaneous adoptive transfer of BMDCs and T cells from CREMalphaTg into NemoDeltahepa mice ameliorated markers of liver injury and hepatitis. CONCLUSIONS: Our results demonstrate that overexpression of CREMalpha in T cells changes the inflammatory milieu, attenuating initiation and progression of CLD. Unexpectedly, our study indicates that CREMalpha transgenic T cells shift chronic inflammation in NemoDeltahepa livers towards a protective Treg response. PMID- 27686097 TI - HIF-2alpha phosphorylation by CK1delta promotes erythropoietin secretion in liver cancer cells under hypoxia. AB - Hypoxia inducible factor 2 (HIF-2) is a transcriptional activator implicated in the cellular response to hypoxia. Regulation of its inducible subunit, HIF-2alpha (also known as EPAS1), involves post-translational modifications. Here, we demonstrate that casein kinase 1delta (CK1delta; also known as CSNK1D) phosphorylates HIF-2alpha at Ser383 and Thr528 in vitro We found that disruption of these phosphorylation sites, and silencing or chemical inhibition of CK1delta, reduced the expression of HIF-2 target genes and the secretion of erythropoietin (EPO) in two hepatic cancer cell lines, Huh7 and HepG2, without affecting the levels of HIF-2alpha protein expression. Furthermore, when CK1delta-dependent phosphorylation of HIF-2alpha was inhibited, we observed substantial cytoplasmic mislocalization of HIF-2alpha, which was reversed upon the addition of the nuclear protein export inhibitor leptomycin B. Taken together, these data suggest that CK1delta enhances EPO secretion from liver cancer cells under hypoxia by modifying HIF-2alpha and promoting its nuclear accumulation. This modification represents a new mechanism of HIF-2 regulation that might allow HIF isoforms to undertake differing functions. PMID- 27686099 TI - Older age is associated with more MRI-detected inflammation in hand and foot joints. AB - OBJECTIVES: Although MRI is recommended for diagnostic use in detecting joint inflammation, its value in clinical practice has not been settled. Older symptom free persons show more MRI-detected inflammation in their hands and feet. Within arthritis patients, a similar effect could be present (a general age effect). The association of age with MRI inflammation could also be enhanced by disease (disease-dependent age effect). Because both effects could have diagnostic consequences, we evaluated the association between age-at-onset and MRI-detected inflammation in early arthritis and RA. METHODS: Unilateral contrast-enhanced MRI of the MCP joint, wrist and MTP joints was performed in 589 newly presenting early arthritis patients, of whom 229 had RA. Bone marrow oedema, synovitis and tenosynovitis were summed, yielding the MRI inflammation score. MRI findings were associated with age and compared with those of 193 (previously reported) symptom free controls. RESULTS: Early arthritis and RA-patients had, respectively, 2.6 (95% CI: 2.3, 3.0, P < 0.001) and 3.7 times (95% CI: 3.2, 4.3, P < 0.001) higher MRI inflammation scores than controls (adjusted for age). At higher age of onset, early arthritis and RA patients had higher MRI inflammation scores (1.03/year, P < 0.001). A similar effect was observed in controls (1.03/year, P < 0.001). The interaction term age*group (arthritis/RA vs controls) was non-significant (P = 0.80 and P = 0.23), suggesting that the age effect was not disease dependent. At the joint level, older RA patients had more extended MRI inflammation, but the preferential locations were similar. CONCLUSION: Older age is associated with more MRI-detected inflammation, and the effect was similar in arthritis and controls. This age effect should be considered when interpreting hand and foot MRI for diagnostic purposes. PMID- 27686100 TI - The PTPN22 R620W polymorphism in anti-neutrophil cytoplasmic antibody-associated vasculitis in Mexican Mestizos. PMID- 27686098 TI - REV-ERBalpha influences the stability and nuclear localization of the glucocorticoid receptor. AB - REV-ERBalpha (encoded by Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, encoded by Nr3c1) influences similar processes, but is not part of the circadian clock, although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes, we studied the interplay between these two nuclear receptors. We found that REV-ERBalpha binds to the C-terminal portion and GR to the N-terminal portion of HSP90alpha and HSP90beta, a chaperone responsible for the activation of proteins to ensure survival of a cell. The presence of REV ERBalpha influences the stability and nuclear localization of GR by an unknown mechanism, thereby affecting expression of GR target genes, such as IkappaBalpha (Nfkbia) and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence the transcriptional potential of each other. This indicates that the transcriptional landscape is strongly dependent on dynamic processes at the protein level. PMID- 27686102 TI - Letter by Mattingly et al Regarding Article, "Endovascular Hypothermia in Acute Ischemic Stroke: Pilot Study of Selective Intra-Arterial Cold Saline Infusion". PMID- 27686101 TI - The role of female hormonal factors in the development of rheumatoid arthritis. AB - RA is the most common chronic systemic autoimmune disease, with a higher prevalence in women, suggesting female hormonal factors play a role in the development of the disease. However, many controversies still exist. The aim of this review was to appraise data from recent research concerning female hormonal factors and their association with RA disease development. The study of female hormonal factors is challenging because serum levels may differ throughout a woman's lifetime and interact with various environmental, immunological, genetic and endocrine factors influencing the development of autoimmunity. As some female hormonal factors may be potentially modifiable, understanding their impact on RA development is clinically relevant and may result in specific preventive interventions in high-risk populations. PMID- 27686103 TI - Response by Chen et al to Letter Regarding Article, "Endovascular Hypothermia in Acute Ischemic Stroke: A Pilot Study of Selective Intra-Arterial Cold Saline Infusion". PMID- 27686104 TI - Validation of Noninvasive In Vivo Compound Ultrasound Strain Imaging Using Histologic Plaque Vulnerability Features. AB - BACKGROUND AND PURPOSE: Carotid plaque rupture is a major cause of stroke. Key issue for risk stratification is early identification of rupture-prone plaques. A noninvasive technique, compound ultrasound strain imaging, was developed providing high-resolution radial deformation/strain images of atherosclerotic plaques. This study aims at in vivo validation of compound ultrasound strain imaging in patients by relating the measured strains to typical features of vulnerable plaques derived from histology after carotid endarterectomy. MATERIALS AND METHODS: Strains were measured in 34 severely stenotic (>70%) carotid arteries at the culprit lesion site within 48 hours before carotid endarterectomy. In all cases, the lumen-wall boundary was identifiable on B-mode ultrasound, and the imaged cross-section did not move out of the imaging plane from systole to diastole. After endarterectomy, the plaques were processed using a validated histology analysis technique. RESULTS: Locally elevated strain values were observed in regions containing predominantly components related to plaque vulnerability, whereas lower values were observed in fibrous, collagen-rich plaques. The median strain of the inner plaque layer (1 mm thickness) was significantly higher (P<0.01) for (fibro)atheromatous (n=20, strain=0.27%) than that for fibrous plaques (n=14, strain=-0.75%). Also, a significantly larger area percentage of the inner layer revealed strains above 0.5% for (fibro)atheromatous (45.30%) compared with fibrous plaques (31.59%). (Fibro)atheromatous plaques were detected with a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 86%, 88%, and 71%, respectively. Strain did not significantly correlate with fibrous cap thickness, smooth muscle cell, or macrophage concentration. CONCLUSIONS: Compound ultrasound strain imaging allows differentiating (fibro)atheromatous from fibrous carotid artery plaques. PMID- 27686105 TI - Histomorphologic features of early gastric carcinoma treated by endoscopic submucosal dissection: relation to efficiency of endoscopic resection. AB - OBJECTIVE: Early gastric cancer (EGC) is defined as cancer invasion confined to the mucosa or submucosa, irrespective of lymph node metastasis. Recently endoscopic submucosal dissection (ESD) has been widely accepted for the treatment for dysplasia and EGC without lymph node metastases. While the method has been advanced in Far East countries, ESD is still being developed in Europe and has not gained enough popularity although it has been recommended as the treatment of choice for superficial gastric neoplastic lesions by European Society of Gastrointestinal Endoscopy (ESGE) in 2015. METHODS: The aim of the study was to perform a retrospective analysis of clinical and histomorphologic features of 58 cases of EGCs removed by ESD in a university hospital in Western Pomerania in Poland and to evaluate factors related to the efficiency of ESD resection. RESULTS: With univariate analysis, indications for ESD with the highest R0 rate were found in EGCs limited to mucosa (T1a, small mucosal, M), without muscularis mucosa invasion, localised in the middle/lower part of stomach and intestinal type in histological examination. The R0 complete resection rate was significantly (p < 0.0001) lower for T1b than that for T1a tumours (21.4% vs. 100%). Tumours with submucosal involvement were associated with lower efficiency of ESD procedure. CONCLUSIONS: Our data showed that in EGCs with favourable histomorphologic characteristics, ESD seemed to be a totally efficient and safe method of treatment in a European small-volume centre. R0 resection rate reached 81.1% of cases and median time of the ESD procedure was 61.5 min. PMID- 27686106 TI - Biological underpinnings of trauma and post-traumatic stress disorder: focusing on genetics and epigenetics. AB - Certain individuals are more susceptible to stress and trauma, as well as the physical and mental health consequences following such exposure, including risk for post-traumatic stress disorder (PTSD). This differing vulnerability is likely to be influenced by genetic predisposition and specific characteristics of the stress itself (nature, intensity and duration), as well as epigenetic mechanisms. In this review we provide an overview of research findings in this field. We highlight some of the key genetic risk factors identified for PTSD, and the evidence that epigenetic processes might play a role in the biological response to trauma, as well as being potential biomarkers of PTSD risk. We also discuss important considerations for future research in this area. PMID- 27686108 TI - Formulating a novel prognostic index for diffuse large B-cell lymphoma: T cells break the SILence. PMID- 27686107 TI - Development of a mobile phone-based intervention to improve adherence to secondary prevention of coronary heart disease in China. AB - Coronary heart disease (CHD) is a major disease burden globally and in China, but secondary prevention among CHD patients remains insufficient. Mobile health (mHealth) technology holds promise for improving secondary prevention but few previous studies included both provider-facing and patient-directed measures. We conducted a physician needs assessment survey (n = 59), physician interviews (n = 6), one focus group and a short cellphone message validation survey (n = 14) in Shanghai and Hainan, China. Based on these results, we developed a multifaceted mHealth intervention that includes: (1) a provider-facing bilingual mobile app guiding prescription of evidence-based medications for secondary prevention and (2) a patient-directed short messaging system automatically sending reminders to patients regarding medication adherence and lifestyle changes (4-5 messages per week for 12 weeks). This combined intervention has the potential to improve secondary prevention of CHD and to be adapted to other countries and healthcare conditions. PMID- 27686110 TI - A comparative evaluation of off-the-shelf distributed semantic representations for modelling behavioural data. AB - In this paper we carry out an extensive comparison of many off-the-shelf distributed semantic vectors representations of words, for the purpose of making predictions about behavioural results or human annotations of data. In doing this comparison we also provide a guide for how vector similarity computations can be used to make such predictions, and introduce many resources available both in terms of datasets and of vector representations. Finally, we discuss the shortcomings of this approach and future research directions that might address them. PMID- 27686109 TI - Pharmacokinetic and pharmacodynamic evaluation of ibrutinib for the treatment of chronic lymphocytic leukemia: rationale for lower doses. AB - INTRODUCTION: Ibrutinib, a first-in-class covalent inhibitor of Bruton's tyrosine kinase (BTK), is approved in many countries for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and for previously untreated disease with a 17p deletion and, most recently, as a frontline therapy for CLL. In controlled trials in CLL, ibrutinib produced high response rates and improved survival in both the frontline and relapsed settings. While ibrutinib controls CLL with impressive efficacy, it only infrequently induces complete remissions, particularly of relapsed CLL, and does not eradicate minimal residual disease. Finally, ibrutinib is extremely expensive, has off-target toxicities, and requires indefinite therapy. Areas covered: In this article, we provide an overview of the CLL therapeutic landscape and discuss the pharmacokinetic and pharmacodynamic aspects of ibrutinib. Major clinical trials of ibrutinib in CLL are summarized, and its safety profile explored. Expert opinion: Ibrutinib represents a transformative advance in CLL management and has validated BTK as a therapeutic target in this disease, but has some limitations, leading to the emergence of other BTK inhibitors and mechanism-based combination strategies. Given complete BTK occupancy at lower doses of ibrutinib and declining levels of BTK on ibrutinib therapy, lower doses of ibrutinib in CLL are being explored. PMID- 27686112 TI - Comparison of in silico tools for binding site prediction applied for structure based design of autolysin inhibitors. AB - Autolysin E (AtlE) is a bacteriolytic enzyme which plays an important role in division and growth of bacterial cells and therefore represents a promising potential drug target. Its 3D structure has been recently elucidated. We used in silico prediction tools to study substrate or ligand (inhibitor) binding regions of AtlE. We applied several freely available tools and a commercial tool for binding site identification and compared results of the prediction. Calculation time, number of predictions and output data provided by specific software vary according to the different approaches utilized by specific method categories. Despite different approaches, binding sites in similar locations on the protein were predicted. Specific amino acid residues that form these binding sites were predicted as binding residues. The predicted residues, especially those with predicted highest conservation score, could theoretically have catalytic and binding properties. According to our results, we assume that E138, which has the highest conservation score, is the catalytic residue and F161, G162 and Y224, which are also highly conserved, are responsible for substrate binding. Ligands developed with binding specificity towards these residues could inhibit the catalysis and binding of the substrate of AtlE. The molecules with inhibitory potency could therefore represent potential new antibacterial agents. PMID- 27686114 TI - Working with sports organizations and teams. AB - Athletes and coaches at all competitive levels will utilize sports performance and psychiatric services at very high rates if the services are offered on-site and free of charge and are broad in scope and culturally sensitive. Services should be available throughout the team year and cover areas such as team building, mental preparation, stress control, substance prevention, sleep and energy regulation, injury recovery, crisis intervention, and mental disorder treatment. The staff offering these services should be diverse by gender, profession, and culture, and the fees should be paid by the organization. When these services are endorsed by the team's leaders and integrated with the athletic training/medical/player development staff, their utilization will grow quickly and lead to positive outcomes individually and collectively. PMID- 27686113 TI - Practical considerations for the application of ear simulators in the calibration of audiometers in the extended high frequency region. AB - OBJECTIVE: Calibration service providers for audiometric equipment often encounter impracticalities in fully implementing the International Electrotechnical Commission (IEC) guidelines for the extended high frequency region. This report evaluates some of the work-around solutions sometimes employed in practice and the implications these have for audiometer calibration results and uncertainties. DESIGN: The impact of using four different microphone configurations on the ear simulator calibration in the frequency range 125 Hz to 20 kHz, and especially in the extended high frequency range from 10 kHz to 20 kHz, was investigated, at a range of temperatures. RESULTS: Variations in the response of the ear simulator of up to 6 dB were observed with the different microphone configurations. In addition, using the microphone without its protection grid produced a dip in the high frequency response of approximately 15 dB. CONCLUSION: While deviation from the practices required in IEC standards is not recommended, replacing the microphone protection grid with a specially fabricated collar (essentially a grid with the top removed) was found to constrain deviations in response to within +/-2 dB. It was also concluded that simply removing the microphone protection grid resulted in a wholly unsatisfactory performance. PMID- 27686111 TI - Using precise word timing information improves decoding accuracy in a multiband accelerated multimodal reading experiment. AB - The blood-oxygen-level-dependent (BOLD) signal measured in functional magnetic resonance imaging (fMRI) experiments is generally regarded as sluggish and poorly suited for probing neural function at the rapid timescales involved in sentence comprehension. However, recent studies have shown the value of acquiring data with very short repetition times (TRs), not merely in terms of improvements in contrast to noise ratio (CNR) through averaging, but also in terms of additional fine-grained temporal information. Using multiband-accelerated fMRI, we achieved whole-brain scans at 3-mm resolution with a TR of just 500 ms at both 3T and 7T field strengths. By taking advantage of word timing information, we found that word decoding accuracy across two separate sets of scan sessions improved significantly, with better overall performance at 7T than at 3T. The effect of TR was also investigated; we found that substantial word timing information can be extracted using fast TRs, with diminishing benefits beyond TRs of 1000 ms. PMID- 27686115 TI - Time-of-day affects prospective memory differently in younger and older adults. AB - The goal of this study was to investigate the impact of circadian arousal on prospective memory performance as a function of age. We tested a younger (18-34 years) and an older group (56-95 years) of participants on- and off-peak with regard to their circadian arousal patterns in a computer-based laboratory experiment. For the prospective memory task, participants had to press a particular key whenever specific target words appeared in an ongoing concreteness judgment task. The results showed that prospective memory performance was better on- than off-peak in younger but not older participants. Younger participants consistently outperformed older participants in all conditions. We conclude that prospective remembering underlies time-of-day effects which most likely reflect controlled processes. PMID- 27686116 TI - Use of non-antiretroviral drugs among individuals with and without HIV-infection: a Danish nationwide study. AB - AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non antiretroviral drugs. Data were analyzed according to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median age: 37; 76.4% males). Overall, the HIV-infected population had a higher use of non-antiretroviral drugs compared to the background population. Whereas, the use of non-antiretroviral drugs in the HIV-infected population only changed marginally with time, the use in the background population increased considerably. Thus, use in the HIV-infected population only differed marginally from that of the background population in recent years. This difference was most pronounced in men who have sex with men (MSM). CONCLUSION: Compared to the background population, HIV infected individuals have increased use of non-antiretroviral drugs. The excess use is mainly observed in MSM and has decreased with calendar time, why it in recent years only differs marginally from that observed in the background population. PMID- 27686117 TI - Kinematical analysis of the V2 ski skating technique: A longitudinal study. AB - To characterise timing of movements and evaluate performance effects of technique alterations in V2 ski skating, 13 elite male cross-country skiers (age, 23 +/- 2 years; stature, 182 +/- 6 cm; body mass, 76 +/- 8 kg; V2 VO2max, 79.3 +/- 4.4 mL . kg-1 . min-1) were tested four times during the preparation and competition phase on a roller ski treadmill. Each test consisted of submaximal intensities of exercise for determination of oxygen cost followed by one 1000-m performance test. Hip movement (from accelerometer data) and joint angles (2D video) were determined for high-intensity exercise (6 degrees and 3.5 m . s-1; ~ 97-100% of VO2peak). Each ski thrust consisted of three phases: gliding phase (18-50% of cycle time), poling phase (50-70% of cycle time), and kick phase (70-78% of cycle time). Flexion/extension of the hip initiated all phases, followed by the respective joints in legs and arms. Mixed-model analysis, adjusting for systematic time-point effects, identified that both reduced vertical hip acceleration and increased cycle time gave a small likely reduction in oxygen cost and 1000-m time. In conclusion, well-developed hip movement is a key characteristic of the V2 technique for elite-standard skiers' long-term performance development. PMID- 27686118 TI - Red blood cell storage age - what we know from clinical trials. PMID- 27686120 TI - Introduction: Central Questions about Personality: Orgins, Differences, and Malleability. PMID- 27686119 TI - Changing prevalence and resistance patterns in children with drug-resistant tuberculosis in Mumbai. AB - BACKGROUND: The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. AIM: To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. METHODS: A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B. J. Wadia Hospital for Children, Mumbai. Children were defined as having DR TB on the basis of drug susceptibility testing (DST) of Mycobacterium tuberculosis grown on culture of body fluids (in the case of extra pulmonary TB) or from gastric lavage/bronchi-alveolar lavage/sputum in patients with pulmonary TB or from DST of the contacts. The prevalence of DR TB was calculated and the type of DR was evaluated yearly and in the pre-2010 and post-2010 eras. RESULTS: The overall prevalence of DR TB was 86 (6.6%) with an increase from 23 (5.6%) patients pre-2010 to 63 (7%) post-2010 (P = 0.40). Nine (10.4%) patients were diagnosed on the basis of contact with a parent with DR TB. Overall fluoroquinolone resistance increased from 9 (39.1%) pre-2010 to 59 (93.7%) post 2010 (P = 0.0001): moxifloxacin resistance increased from 2 (8.7%) to 29 (46%) (P = 0.0018) and ofloxacin resistance increased from 7 (30.4%) to 30 (47.6%) (P = 0.14). Ethionamide resistance also increased from 6 (26.1%) to 31 (49.2%) (P = 0.04), aminoglycoside resistance was one (4.3%) pre-2010 and 12 (19%) post-2010 (P = 0.17) and resistance remained virtually the same for both amikacin [0 pre 2010 and 6 (9.5%) after 2010] and kanamycin [one (4.3%) pre- and 6 (9.5%) post 2010]. Of the first-line drugs, resistance remained the same for isoniazid [23 (100%) to 61 (96.8%)], rifampicin [22 (95.7%) to 51 (80.9%),P = 0.17], pyrazinamide [15 (65.2%) to 35 (55.6%), P = 0.47], ethambutol [14 (60.9%) to 38 (60.3%), P = 1.00] and streptomycin [19 (82.6%) to 50 (79.4%), P = 1.00]. Resistance to PAS remained unchanged [2 (8.7%) to 5 (7.9%), P = 1.00]. CONCLUSION: There is increasing resistance to second-line anti-tuberculosis (ATT) drugs, particularly flouroquinolones and ethionamide. Hence, there is an urgent need to avoid the use of ATT drugs for non-tuberculous infection and to increase surveillance for DR TB in adults as MDR TB in children is usually through contact with an adult with infectious MDR TB. PMID- 27686121 TI - Design, synthesis, and evaluation of pyrazolo-pyrazole derivatives on Methylisocitratelyase of Pseudomonas aeruginosa: in silico and in vitro study. AB - Pseudomonas aeruginosa is an opportunistic micro-organism causing diseases both in animals and humans. In case of human pathology, the role of P. aeruginosa is one of the major concerns in intensive care septicemia. Presently, the drug resistance strains of P. aeruginosa are arising mainly by developing multiple mechanisms due to its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. As a result, there is a direct need to invent new drugs so that they may restrict the outbreak of multidrug resistant strains. Virtual high-throughput insilico screening, which helps to identify the chemical ligands that bind to the enzymes, is an important tool in drug discovery and the drugs discovered in this way are clinically tested. In this study, Methylisocitratelyase (MICL), which is essential for the survival of the bacterium and which doesn't show any similarity with the humans, was selected to evaluate the functions of high-affinity inhibitors (PPI-analogs) that are identified using the virtual screening approach. By adopting the computational analysis tools, structural, functional, and inhibitor interactions of MICL against P. aeruginosa were identified. The PPIA-32 is found to be the best binding interactions with MICL. PPIA-32 reduces the binding affinity for substrate to residues required for MICL enzyme activity and also Root Mean Square Deviation simulations show the most stable nature of PPA32-MICL(complex) than that of MICL alone, thereby effectively inhibiting the growth of virulent P. aeruginosa. To our surprise, the same phenomenon is also identified with other gram-negative bacteria like Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi. PMID- 27686123 TI - Biomimetic Designing of Functional Silk Nanotopography Using Self-assembly. AB - In nature inorganic-organic building units create multifunctional hierarchical architectures. Organic silk protein is particularly attractive in this respect because of its micro-nanoscale structural blocks that are attributed to sophisticated hierarchical assembly imparting flexibility and compressibility to designed biohybrid materials. In the present study, aqueous silk fibroin is assembled to form nano/microtopography on inorganic silica surface via a facile diffusion-limited aggregation process. This process is driven by electrostatic interaction and only possible at a specified aminated surface chemistry. The self assembled topography depends on the age and concentration of protein solution as well as on the surface charge distribution of the template. The self-assembled silk trails closely resemble natural cypress leaf architecture, which is considered a structural analogue of neuronal cortex. This assembled surface significantly enhances anchorage of neuronal cell and cytoskeletal extensions, providing an effective nano/microtopographical cue for cellular recognition and guidance. PMID- 27686122 TI - Control of non-apoptotic nurse cell death by engulfment genes in Drosophila. AB - Programmed cell death occurs as a normal part of oocyte development in Drosophila. For each egg that is formed, 15 germline-derived nurse cells transfer their cytoplasmic contents into the oocyte and die. Disruption of apoptosis or autophagy only partially inhibits the death of the nurse cells, indicating that other mechanisms significantly contribute to nurse cell death. Recently, we demonstrated that the surrounding stretch follicle cells non-autonomously promote nurse cell death during late oogenesis and that phagocytosis genes including draper, ced-12, and the JNK pathway are crucial for this process. When phagocytosis genes are inhibited in the follicle cells, events specifically associated with death of the nurse cells are impaired. Death of the nurse cells is not completely blocked in draper mutants, suggesting that other engulfment receptors are involved. Indeed, we found that the integrin subunit, alphaPS3, is enriched on stretch follicle cells during late oogenesis and is required for elimination of the nurse cells. Moreover, double mutant analysis revealed that integrins act in parallel to draper. Death of nurse cells in the Drosophila ovary is a unique example of programmed cell death that is both non-apoptotic and non cell autonomously controlled. PMID- 27686126 TI - Relationship between hsTnI and coronary stenosis in asymptomatic women with rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is a condition associated with accelerated progression of atherosclerosis in affected individuals. Myocardial assessment using exercise testing in such patients, however, is often difficult to perform. Our objective was to determine the factors associated with severe coronary stenosis using computed tomography (CT) angiography of the coronary arteries in asymptomatic patients with RA. METHODS: Forty-four women with RA were examined using CT angiography to detect atherosclerotic involvement and significant coronary stenosis (>50 %). CT findings were correlated with the cardiovascular risk score, and with classical and most recent parameters of atherosclerosis. RESULTS: CT angiography of the coronary arteries revealed severe stenosis (>70 %) in 9 % of patients. High-sensitivity troponin I level was associated with severe coronary stenosis (odds ratio 6.37; 95 % confidence interval 1.53 - 26.48; P = 0.011). Adjustment for confounders did not alter this result (P = 0.039). In contrast, classical and modified Systemic Coronary Risk Evaluation scores had no value in predicting severe stenosis (P >= 0.49). CONCLUSION: The present study showed the possible benefits of a coronary CT angiography in women with RA and asymptomatic ischemic coronary heart disease. Increased levels of high sensitivity troponin I may be a potential indication for this type of examination. However, further studies are needed to confirm these results. PMID- 27686125 TI - Challenges of implementing a large scale larviciding campaign against malaria in rural Burkina Faso - lessons learned and recommendations derived from the EMIRA project. AB - BACKGROUND: Recent malaria control and elimination attempts show remarkable success in several parts of sub-Saharan Africa. Vector control via larval source management represents a new and to date underrepresented approach in low income countries to further reduce malaria transmission. Although the positive impact of such campaigns on malaria incidence has been researched, there is a lack of data on which prerequisites are needed for implementing such programs on a routine basis on large scale. Our objectives are to point out important steps in implementing an anti-malaria larviciding campaign in a resource and infrastructure restraint setting and share the lessons learned from our experience during a three-year intervention study in rural Burkina Faso. METHODS: We describe the approaches we followed and the challenges that have been encountered during the EMIRA project, a three-year study on the impact of environmental larviciding on vector ecology and human health. An inventory of all performed work packages and associated problems and peculiarities was assembled. RESULTS: Key to the successful implementation of the larviciding program within a health district was the support and infrastructure from the local research center run by the government. This included availability of trained scientific personnel for local project management, data collection and analysis by medical personnel, entomologists and demographers and teams of fieldworkers for the larviciding intervention. A detailed a priori assessment of the environment and vector breeding site ecology was essential to calculate personnel requirements and the need for larvicide and application apparel. In our case of a three-year project, solid funding for the whole duration was an important issue, which restricted the number of possible donors. We found the acquisition of qualified field personnel in fair numbers not to be always easy and training in application techniques and basic entomologic knowledge required several weeks of theoretical and practical formation. A further crucial point was to establish an effective quality control system that ensured the timely verification of larviciding success and facilitated in time data handling. While the experiences of running a larviciding campaign may vary globally, the experiences gained and the methods used in the Nouna health district may be employed in similar settings. CONCLUSIONS: Our observations highlight important components and strategies that should be taken into account when planning and running a similar larviciding program against malaria in a resource limited setting. A strong local partnership, meticulous planning with the possibility of ad-hoc adaption of project components and a reliable source of funding turned out to be crucial factors to successfully accomplish such a project. PMID- 27686124 TI - High attack frequency in patients with angioedema due to C1-inhibitor deficiency is a major determinant in switching to home therapy: a real-life observational study. AB - BACKGROUND: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent attacks of swelling that affect various body sites. Such attacks are a frequent cause of visits to the emergency department and are often treated in the hospital. In recent years, self-administration of C1 inhibitor (C1-INH) concentrates at home has become an increasingly used option, with a positive impact on patient outcomes and quality of life. METHODS: This was an observational study of 6 months' duration in 56 patients with C1-INH-HAE referred to a HAE center in southern Italy. The patients received three types of treatment for their swelling attacks: C1-INH concentrates administered at home (n = 25); icatibant administered at home (n = 12); and C1-INH concentrates administered in the hospital (n = 19). The objectives of this observational study were to compare therapy compliance (defined as the proportion of treated attacks) and quality of life in home- and hospital-treated patients, and to identify factors associated with the decision to use home therapy. RESULTS: Overall, 918 attacks were reported over 6 months, of which 544 (59.2 %) were treated. Total number of reported attacks and the mean (+/-SD) number of attacks per patient, respectively, in the three groups were: 611 and 24.4 (+/-26.1) for home-based C1 INH; 191 and 15.9 (+/-12.0) for home-based icatibant; 166 and 6.1 (+/-6.5) for hospital-based C1-INH. Differences in attack frequency between home- and hospital based treatments were statistically significant (p = 0.002), while patient demographic characteristics and the disease severity score did not correlate with the use of home therapy. Compliance with therapy was significantly better with home-based therapy (71.2 % of treated attacks with C1-INH and 44.0 % with icatibant) than with hospital-based therapy (21.6 %, p = 0.003). Quality of life showed an opposite trend, with patients on hospital-based treatment reporting the highest quality of life. CONCLUSIONS: Home-based therapy was associated with better compliance compared with hospital-based therapy. The choice to adopt home based therapy appeared to correlate with a high attack frequency. Home-based therapy is a valid treatment option for patients with C1-INH-HAE and should be offered to all such patients, and especially to those with high attack frequency. PMID- 27686128 TI - Insect odorant receptor trafficking requires calmodulin. AB - BACKGROUND: Like most animals, insects rely on their olfactory systems for finding food and mates and in avoiding noxious chemicals and predators. Most insect olfactory neurons express an odorant-specific odorant receptor (OR) along with Orco, the olfactory co-receptor. Orco binds ORs and permits their trafficking to the dendrites of antennal olfactory sensory neurons (OSNs), where together, they are suggested to form heteromeric ligand-gated non-selective cation channels. While most amino acid residues in Orco are well conserved across insect orders, one especially well-conserved region in Orco's second intracellular loop is a putative calmodulin (CaM) binding site (CBS). In this study, we explore the relationship between Orco and CaM in vivo in the olfactory neurons of Drosophila melanogaster. RESULTS: We first found OSN-specific knock down of CaM at the onset of OSN development disrupts the spontaneous firing of OSNs and reduces Orco trafficking to the ciliated dendrites of OSNs without affecting their morphology. We then generated a series of Orco CBS mutant proteins and found that none of them rescue the Orco-null Orco 1 mutant phenotype, which is characterized by an OR protein trafficking defect that blocks spontaneous and odorant-evoked OSN activity. In contrast to an identically constructed wild-type form of Orco that does rescue the Orco 1 phenotype, all the Orco CBS mutants remain stuck in the OSN soma, preventing even the smallest odorant-evoked response. Last, we found CaM's modulation of OR trafficking is dependent on activity. Knock-down of CaM in all Orco-positive OSNs after OR expression is well established has little effect on olfactory responsiveness alone. When combined with an extended exposure to odorant, however, this late onset CaM knock-down significantly reduces both olfactory sensitivity and the trafficking of Orco only to the ciliated dendrites of OSNs that respond to the exposed odorant. CONCLUSIONS: In this study, we show CaM regulates OR trafficking and olfactory responses in vivo in Drosophila olfactory neurons via a well conserved binding site on the olfactory co-receptor Orco. As CaM's modulation of Orco seems to be dependent on activity, we propose a model in which the CaM/Orco interaction allows insect OSNs to maintain appropriate dendritic levels of OR regardless of environmental odorant concentrations. PMID- 27686129 TI - Spontaneous Gastric Perforation in Two Adolescents. AB - BACKGROUND Spontaneous gastric perforation is a rare clinical disorder. The majority of the available data have been reported in the neonatal age group. There are a few cases of spontaneous gastric perforation in preschool children. To our knowledge, there is no published information on spontaneous gastric perforation in older children and adolescents. CASE REPORT We describe the presentation and clinical course of two adolescent children who presented with spontaneous gastric perforation. Both children presented with acute onset abdominal pain, which progressively worsened. In both cases, the patient were taken urgently to the operating room after imaging studies had shown pneumoperitoneum. In both cases, surgery revealed gastric perforation with no obvious etiology, specifically no -ulcer, inflammation, or other pathology. CONCLUSIONS These two cases highlight the importance of including spontaneous gastric perforation, not just the typical duodenal/gastric ulcer, in the differential of a patient with severe abdominal pain and distension, who has imaging showing pneumoperitoneum. PMID- 27686127 TI - qKAT: a high-throughput qPCR method for KIR gene copy number and haplotype determination. AB - Killer cell immunoglobulin-like receptors (KIRs), expressed on natural killer cells and T cells, have considerable biomedical relevance playing significant roles in immunity, pregnancy and transplantation. The KIR locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes KIRs technically laborious and expensive to type. To aid the investigation of KIRs in human disease we developed a high throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each KIR locus. We used reference DNA samples to validate the accuracy and a cohort of 1698 individuals to evaluate capability for precise copy number discrimination. The method provides improved information and identifies KIR haplotype alterations that were not previously visible using other approaches. PMID- 27686130 TI - Efficacy of anorectal biofeedback in scleroderma patients with fecal incontinence: a case-control study. AB - OBJECTIVE: To determine whether anorectal biofeedback therapy can improve the symptoms of fecal incontinence (FI) in patients with scleroderma when compared to patients with functional FI, and also whether there is any effect on anorectal physiology or quality of life (QOL). FI in patients with scleroderma is highly prevalent and is associated with significant loss of QOL. Biofeedback has been proven to be an effective treatment for functional FI, but there are no data to support its use in scleroderma. MATERIALS AND METHODS: 13 consecutive female patients (median age 59, IQR 47-65 years) with scleroderma, and 26 age- and parity-matched female patients with functional FI (disease controls, 2:1), underwent biofeedback therapy for management of FI. Fecal incontinence severity index (FISI), anorectal physiology, feeling of control and QOL were collected before and after 6 weeks of biofeedback therapy, with additional scoring repeated at 6-month follow-up. RESULTS: After biofeedback treatment FISI, feeling of control and QOL significantly improved in both groups (p < 0.005). There was no difference in the degree in improvement in physiology, FISI or QOL between scleroderma patients and functional FI patients. Long-term improvement in FISI and control were seen in both groups and for QOL only in the scleroderma cohort (p < 0.05). CONCLUSIONS: Patients with scleroderma benefit from biofeedback therapy to the same extent as that achieved in patients with functional FI. There are significant improvements in symptoms, physiology and QOL. Biofeedback is an effective, low-risk treatment option in this patient group. PMID- 27686131 TI - 1000 cases of tubeless video-assisted thoracic surgery at the Rome Tor Vergata University. AB - In the early 2000s, the 'Awake Thoracic Surgery Research Group' at Tor Vergata University began a program of thoracic operations in awake nonintubated patients. To our knowledge this was the first program created with this specific purpose. Since then over 1000 tubeless operations have been carried out successfully, making this series one of the widest in the world. Both nononcologic and oncologic conditions were successively approached and major operations for lung cancer are now being performed. Uniportal access was progressively adopted with significant positive outcomes in postoperative recovery, patient acceptance and economical costs. Failure rates due to patient's intolerance and open surgery conversion are progressively reducing. Tubeless thoracic surgery can be accomplished in a safe manner with effective results. PMID- 27686132 TI - Effect of nine diets on mRNAs of phase-II conjugation enzymes in livers of mice. AB - 1. Phase-II enzymes are important in metabolizing many xenobiotics including prescription drugs and chemical carcinogens. Whereas it is known that diet can alter the expression of phase-II conjugation enzymes, the previous studies are limited in using only two or three diets and examining only a few enzymes. 2. Adult male C57BL6 mice were fed one of nine diets for 3 weeks. Of the 87 genes encoding major hepatic phase-II enzymes, approximately one-half (43) were altered by at least one diet. Diet restriction altered the hepatic expression of the most genes encoding phase-II enzymes (27), followed by lab chow (15), atherogenic diet (13), high-fat diet (10), western diet (7), high-fructose diet (5), and essential fatty acid-deficient diet (3), whereas the low n-3 fatty acid diet had no effect on the hepatic expression of these phase-II enzymes. 3. This comprehensive study provides detailed information on which conjugation enzymes are changed by these diets, and these data can be used to further investigate the mechanism for these changes in messenger RNAs, and whether these changes result in alterations in enzyme activity and drug action. PMID- 27686134 TI - Functioning of medial olivocochlear bundle in right- and left-handed individuals. AB - Functional symmetry of medial olivocochlear bundle (MOCB) as a function of handedness remains to be well investigated. The current study aimed to assess the functional symmetry of MOCB through contralateral inhibition of otoacoustic emissions (OAEs) in right- and left-handed individuals. Thirteen left-handed and 13 right-handed individuals in the age range of 19-25 years participated. Behavioural experiment involved measuring speech perception in noise and vocal reaction time. Physiological experiment involved measuring the contralateral inhibition of OAEs in both the ears of participants. Findings of the current study revealed lack of functional asymmetry in right- as well as left-handed individuals. Results of the current study suggest that right- as well as left handed individuals do not demonstrate functional asymmetry at the level of descending auditory pathways unlike the higher cortical centres. PMID- 27686133 TI - Potential allelopathic azaphilones produced by the endophytic Chaetomium globosum TY1 inhabited in Ginkgo biloba using the one strain-many compounds method. AB - On the basis of the one strain-many compounds strategy, seven azaphilones, including Chaetomugilin A (1), D (2), S (3), I (4), J (5), Q (6) and O (7), were isolated from the endophytic Chaetomium globosum TY1. Their structures were identified by NMR and HRESIMS spectrometry data. All azaphilones were evaluated for plant growth regulation using eight species of herbaceous plant seeds seedling growth bioassay, which showed the plant growth influence of the seedling. Among these compounds tested, Chaetomugilin O (7) with tetrahydrofuran exhibited higher response index and lower IC50 values than positive control glyphosate, a broad-spectrum systemic herbicide. 1-3 also showed better or similar inhibit activity to glyphosate. The structure-allelopathic activity relationship analysis of these isolated azaphilones indicates that both tetrahydrofuran and tetrahydrofuran combine with lactones ring groups give potent inhibition of seedling growth. Chaetomugilin O and Chaetomugilin A, D, S could be used to develop natural eco-friendly herbicides. PMID- 27686136 TI - Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1alpha Promote Bone Regeneration via Recruiting Endogenous Stem Cells. AB - The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1alpha (CBD SDF-1alpha). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1alpha could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1alpha-modified DBM scaffolds could efficiently mobilize CD34+ and c-kit+ endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1alpha modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1alpha group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson's trichrome staining showed that the CBD-SDF-1alpha-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1alpha group had superior strength. In conclusion, CBD-SDF-1alpha modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells. PMID- 27686135 TI - Personality traits and clinical/biochemical course in the first year after kidney transplant. AB - BACKGROUND: The relationship between personality and health is frequently studied in scientific research. This study investigated the clinical/biochemical course of kidney transplant patients based on personality traits. METHODS: A longitudinal study assessed 114 kidney transplant patients (men = 68 and women = 46) with an average age of 47.72 years (SD = 11.4). Personality was evaluated using the Brazilian Factorial Personality Inventory (BFP/Big Five Model). Clinical variables were analyzed based on patient charts (estimated glomerular filtration rate (eGFR), hypertension, acute rejection, infection, graft loss, and death). Personality types were assessed by hierarchical cluster analysis. RESULTS: Two groups with personality types were differentiated by psychological characteristics: Cluster 1 - average neuroticism, high surgency, agreeableness and conscientiousness, and low openness; Cluster 2 - high neuroticism, average surgency and agreeableness, average conscientiousness, and low openness. There was no statistically significant difference between the clusters in terms of hypertension, acute infection, graft loss, death, and Human Leukocyte Antigen (HLA) I and II panel reactive antibodies. eGFR was associated with the personality types. Cluster 2 was associated with a better renal function in the 9 month follow-up period after kidney transplantation. CONCLUSION: In this study, patients from Cluster 2 exhibited higher eGFR 9 months after the transplant procedure compared to those from Cluster 1. Monitoring these patients over a longer period may provide a better understanding of the relationship between personality traits and clinical course during the post-transplant period. PMID- 27686137 TI - Effects of categorical representation on visuospatial working memory in autism spectrum disorder. AB - We tested whether individuals with autism spectrum disorder (ASD) are impaired in visuospatial working memory or in the use of the semantic system, in particular in categorization processes at the service of working memory. The performance of high-functioning individuals with ASD (N = 21) in a visual same-different task adapted from Lachmann and van Leeuwen [e.g., Lachmann, T., & van Leeuwen, C. (2010). Representational economy, not processing speed, determines preferred processing strategy of visual patterns. Acta Psychologica, 134(3), 290-298] was compared to those of typically developed controls (N = 25). In a categorical identity task, two successive patterns had to be judged as the same if they belonged to the same equivalence set (cf. Garner, W. R., & Clement, D. E. (1963). Goodness of pattern and pattern uncertainty. Journal of Verbal Learning and Verbal Behavior, 2, 446-452), including all possible rotation and reflection transformations (R&R category), and as different otherwise. In a physical identity task, only patterns that matched in both shape and orientation had to be responded to as the same; all others, including category matches, had to be classified as different. Equivalence sets had different sizes (ESS). Earlier studies showed an increase in reaction time (RT) with increasing ESS and, for the physical identity task, a response conflict for category matching. Both of these effects were interpreted as evidence for a categorical code by which individual patterns are mentally represented. Assuming that categorization processes are deficient in individuals with ASD, we expected no ESS effects and, in the physical identity task, absence of a response conflict for these individuals. In contrast, we found individuals with ASD to be generally as sensitive to ESS as controls, and they showed a response conflict in the physical identity task. Thus, categorical processing seems to be intact in ASD. However, a strong overall group effect was found in RTs: Individuals with ASD are considerably slower than controls. PMID- 27686138 TI - Simulated patients versus seminars to train case history and feedback skills in audiology students: A randomized controlled trial. AB - OBJECTIVE: To compare simulated patients (SP) versus seminars for training audiology students to take a case history and give feedback with adult patients. DESIGN: A randomized controlled trial with cross-over. STUDY SAMPLE: Twenty-four audiology students, five SPs, two clinical educators (CE) and three evaluators. Students were randomly allocated to Group 1 who completed SP then seminar training or Group 2 who completed seminar then SP training. The SP training saw each student work with an SP in a clinic room and receive individualized feedback. The seminar training saw the student group work with a single CE in a lecture room and receive group feedback. All students were assessed taking a case history and giving feedback to an SP before, between, and after the training blocks. RESULTS: Mixed model analyses of derived factors for case history and feedback showed significant (p < 0.05) effects for assessment occasion (i.e. student skills improved with more training) but not for training sequence (i.e. order of training did not affect skill improvements) or training type (i.e. type of training did not affect skill improvements). CONCLUSION: SP training provided no benefit over seminar training in audiology students learning case history and feedback skills with adult patients. PMID- 27686141 TI - Letter to the Editor. PMID- 27686140 TI - Prognosis following infectious spondylodiscitis: work in progress. PMID- 27686139 TI - Resolution of low-velocity control in golf putting differentiates professionals from amateurs. AB - It is difficult for humans to apply small amounts of force precisely during motor control. However, experts who have undergone extended training are thought to be able to control low-velocity movement with precision. We investigated the resolution of motor control in golf putting. A total of 10 professional and 10 high-level amateur golfers participated. Putting distances were 0.6-3.3 m, in increments of 0.3 m. We measured the impact velocity and the club-face angle at impact, and the acceleration profile of the downswing. The professionals showed significantly smaller coefficients of variation with respect to impact velocity and smaller root mean square errors in relation to acceleration profiles than did the amateurs. To examine the resolution of motor control for impact velocity, we investigated intra-participant differences in the impact velocity of the club head at two adjacent distances. We found that professionals had higher velocity precision when putting small distance intervals than did amateurs. That is, professionals had higher resolution of low-velocity control than did high-level amateurs. Our results suggest that outstanding performance at a task involves the ability to recognise small distinctions and to produce appropriate movements. PMID- 27686142 TI - Molybdenum-containing nitrite reductases: Spectroscopic characterization and redox mechanism. AB - OBJECTIVES: This review summarizes the spectroscopic results, which will provide useful suggestions for future research. In addition, the fields that urgently need more information are also advised. BACKGROUND: Nitrite-NO-cGMP has been considered as an important signaling pathway of NO in human cells. To date, all the four known human molybdenum-containing enzymes, xanthine oxidase, aldehyde oxidase, sulfite oxidase, and mitochondrial amidoxime-reducing component, have been shown to function as nitrite reductases under hypoxia by biochemical, cellular, or animal studies. Various spectroscopic techniques have been applied to investigate the structure and catalytic mechanism of these enzymes for more than 20 years. METHODS: We summarize the published data on the applications of UV vis and EPR spectroscopies, and X-ray crystallography in studying nitrite reductase activity of the four human molybdenum-containing enzymes. RESULTS: UV vis has provided useful information on the redox active centers of these enzymes. The utilization of EPR spectroscopy has been critical in determining the coordination and redox status of the Mo center during catalysis. Despite the lack of substrate-bound crystal structures of these nitrite reductases, valuable structural information has been obtained by X-ray crystallography. CONCLUSIONS: To fully understand the catalytic mechanisms of these physiologically/pathologically important nitrite reductases, structural studies on substrate-redox center interaction are needed. PMID- 27686143 TI - Outcome of inflammatory bowel disease patients treated with TNF-alpha inhibitors: two-year follow-up. AB - BACKGROUND: Biological medications, particularly TNF-alpha inhibitors, are used increasingly for active inflammatory bowel disease (IBD). Even though they are superior to many older medications in achieving remission and mucosal healing, primary nonresponse and loss of response remain significant problems, and a remarkable proportion of patients still need surgery at some point. OBJECTIVE: To study the outcome of IBD patients treated with TNF-alpha inhibitors, either infliximab or adalimumab, with a two-year follow-up. PATIENTS AND METHODS: Patient data from the hospital electronic patient documents of IBD patients treated with TNF-alpha inhibitors were studied. The main targets of interest were treatment response, the remission rate and the number of patients operated, as well as reasons for the discontinuation of treatment. Remission was defined both endoscopically and by faecal calprotectin. RESULTS: Altogether 100 patients were included. Only 29% of the patients achieved remission during the two-year follow up. 26% of the Crohn's disease patients and 36% of the ulcerative colitis patients underwent surgery during the follow-up. A significant proportion of patients experienced side effects of the medication (21%) or discontinued the therapy for other reasons (altogether 63%). CONCLUSIONS: In this single centre study of 100 IBD patients treated with TNF-alpha inhibitors, less than one-third of the patients achieved remission, and a significant proportion had side effects and needed surgery during the two-year follow-up. There is an obvious need for more effective therapies with less side effects for IBD patients. PMID- 27686145 TI - High-Level Expression of Toll-Like Receptors on Dendritic Cells in Adult Patients with Burns on >=90% of Total Body Surface Area (TBSA). AB - BACKGROUND As a serious clinical problem, severe burn injury disturbs the immune system, resulting in progressive suppression of immune response. TLRs are associated with immune system activation, but the effect of TLRs levels on circulating cDCs of severe burn injury patients has not been fully assessed. MATERIAL AND METHODS Ten patients with total body surface area (TBSA) burned >90% admitted to our institution were enrolled in this study. We analyzed TLR2, TLR4, and TLR9 expression on the circulating cDCs by using multicolor flow cytometric analysis in patients at 14 days to 28 days after burn injury according to mortality, and We also assessed Demographics, clinical outcomes, organ function, and inflammatory and acute-phase responses. RESULTS No difference in TBSA, sex, age, or number of operations before the first 14 days after injury were observed between surviving and non-surviving burn patients. The levels of TLR2, TLR4, and TLR9 in circulating cDCs were significantly and consistently elevated in all patients compared to age-matched healthy volunteers, and survivors exhibited higher TLR2 and TLR4 values than non-survivors. Of the survivors, TLR2 and TLR4 levels were higher at 28 days than at 14 days after injury, while the difference in TLR9 levels was not significant. TLR2 levels of non-survivors at 28 days after injury decreased, and the TLR4 and TLR9 levels showed no significant difference. CONCLUSIONS TLRs levels in circulating cDCs are highly activated in severe burn injury patients up to 28 days after injury. The low expression of TLR2 in cDCs may be useful as a potential marker predicting the poor prognosis of severe burn patients. PMID- 27686146 TI - Population pharmacokinetics of mycophenolic acid and its glucuronide metabolite in lung transplant recipients with and without cystic fibrosis. AB - 1. Cystic fibrosis (CF) is a disease affecting multiple organs that may reduce the systemic exposure of some drugs. The objective of this work was to characterize and compare the population pharmacokinetics (PK) of the immunosuppressant mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) in adult lung transplant recipients with and without CF (NCF) following repeated oral administration of the prodrug mycophenolate mofetil (MMF). 2. A population PK model was developed, with simultaneous modeling of MPA and MPAG, using nonlinear mixed effects modeling. MPA and MPAG serum concentration-time data were adequately described by a compartmental model including enterohepatic recirculation (EHR). Both MPA and MPAG apparent clearance values were significantly elevated (>65%) in patients with CF (24.1 and 1.95 L/h, respectively) compared to the values in the NCF patients (14.5 and 1.12 L/h, respectively), suggesting a notable influence of CF on MPA absorption and disposition. 3. The population PK model developed from our study successfully characterized the absorption, distribution, elimination and EHR of MPA and the metabolite MPAG in lung transplant recipients with or without CF. This model may help to further understand the impact of CF to the overall clinical effects of MPA therapy including immunosuppression and gastrointestinal side effects. PMID- 27686144 TI - Impact of maternal nutrition in pregnancy and lactation on offspring gut microbial composition and function. AB - Evidence supporting the Developmental Origins of Health and Disease Hypothesis indicates that maternal nutrition in pregnancy has a significant impact on offspring disease risk later in life, likely by modulating developmental processes in utero. Gut microbiota have recently been explored as a potential mediating factor, as dietary components strongly influence microbiota abundance, function and its impact on host physiology. A growing body of evidence has additionally indicated that the intrauterine environment is not sterile as once presumed, indicating that maternal-fetal transmission of microbiota may occur during pregnancy. In this article, we will review the body of literature that supports this emerging hypothesis, as well as highlight the work in relevant animal models demonstrating associations with maternal gestational nutrition and the offspring gut microbiome that may influence offspring physiology and susceptibility to disease. PMID- 27686147 TI - Efficient exciton generation in atomic passivated CdSe/ZnS quantum dots light emitting devices. AB - We demonstrate the first-ever surface modification of green CdSe/ZnS quantum dots (QDs) using bromide anions (Br-) in cetyl trimethylammonium bromide (CTAB). The Br- ions reduced the interparticle spacing between the QDs and induced an effective charge balance in QD light-emitting devices (QLEDs). The fabricated QLEDs exhibited efficient charge injection because of the reduced emission quenching effect and their enhanced thin film morphology. As a result, they exhibited a maximum luminance of 71,000 cd/m2 and an external current efficiency of 6.4 cd/A, both significantly better than those of their counterparts with oleic acid surface ligands. In addition, the lifetime of the Br- treated QD based QLEDs is significantly improved due to ionic passivation at the QDs surface. PMID- 27686148 TI - Lateral opening in the intact beta-barrel assembly machinery captured by cryo-EM. AB - The beta-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E), which is essential for viability in E. coli. BAM promotes the folding and insertion of beta-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a 'lateral gating' motion of the beta-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 A resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex and interactions between BamA, B, D and E, and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM. PMID- 27686149 TI - Estill Voice Training and voice quality control in contemporary commercial singing: an exploratory study. AB - Estill Voice Training (EVT) is a widely known programme for developing vocal skills based on partitioning the process of vocal production in order to reach control of specific structures in the vocal mechanism. The present retrospective small-scale exploratory study aims at reporting preliminary data about the efficacy of EVT - in terms of voice quality control on a specific vocal exercise in contemporary commercial singers with a Certificate of Figure Proficiency (CFP). Thirty-five contemporary commercial singers (professional or semi professional pop and rock singers) with no vocal complaints were recruited. The experimental group was composed of twenty singers who studied EVT and had a CFP. The control group was composed of fifteen singers who studied in Italian contemporary popular music institutions but were not familiar with EVT. Voice quality control was assessed through acoustic and perceptual analysis on a specific vocal exercise requiring sound pitch, perturbation and spectral energy distribution control. The acoustic analysis showed some significant differences between the two groups of singers both in sound perturbation control and spectral energy distribution control, suggesting a higher voice quality control ability for the experimental group. The perceptual evaluation confirmed a higher ability for the experimental group to produce recognizable voice qualities in this specific task. The reported preliminary results seem to suggest EVT as an effective educational system for developing voice quality control ability in contemporary commercial singers. PMID- 27686150 TI - Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma. AB - MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1 antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1 antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p < 0.05). Urinary exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC. PMID- 27686151 TI - Higher prevalence of elevated LDL-C than non-HDL-C and low statin treatment rate in elderly community-dwelling Chinese with high cardiovascular risk. AB - Lipid levels are increasing in all age groups in the Chinese population, but the use of statin treatment in the elderly is not well documented. We examined serum lipids, statin usage and achievement of lipid goals in 3950 subjects aged >=65 years. Established CVD was present in 7.77% of participants and increased CVD risk was common. Elevated LDL-C according to CVD risk level was present in 46.70% of all subjects and was more frequent (p < 0.01) than elevated non-HDL-C at 32.58%. With increasing age, LDL-C was unchanged but triglycerides and non-HDL-C decreased and HDL-C increased. Individuals at moderate risk for CVD had higher TC, LDL-C, and non-HDL-C than low-risk subjects, but the values were lower in high- and very-high-risk individuals, probably because of the use of statin which was 28.57% in high-risk subjects with established CVD and 37.60% in very-high risk individuals, but only 2.62% in those with estimated high-risk and 3.75% in those with high-risk from diabetes. More subjects in each risk group reached the non-HDL-C goal than the LDL-C goal because of the relatively low triglycerides and VLDL-C levels. These findings demonstrate a high prevalence of elevated LDL-C but low rate of statin treatment in elderly community-dwelling Chinese. PMID- 27686152 TI - Loss to follow-up and HIV incidence in female sex workers in Kaiyuan, Yunnan Province China: a nine year longitudinal study. AB - BACKGROUND: Longitudinal studies of female sex workers (FSWs) are vulnerable to loss to follow-up (LTFU) due to this population's high mobility and low willingness to self-identify as FSWs. LTFU in cohort studies is a critical problem and may lead to bias in estimation of incidence and exposure-outcome associations. The aim of this study was to analyze LTFU and HIV incidence and their associated factors in a 9-year longitudinal study of FSWs in Kaiyuan, Yunnan Province, China. METHODS: This analysis includes all HIV-1 seronegative FSWs who were recruited into a prospective study in Kaiyuan with at least one follow-up visit after enrollment from March 2006 to November 2013. Participants were visited in 6-month intervals after enrollment. Their demographic and behavioral data and blood specimens for HIV and sexual transmitted disease testing were collected at enrollment and at each follow-up visit. The administrative censoring date was December 31, 2014. Participants were considered LTFU if their last visit occurred 1 year or more before the administrative censoring date. Univariate and multivariable Cox regression models with time independent variables were used to investigate the hazard ratios (HR) and 95 % confidence intervals (CI) of the factors associated with LTFU and HIV acquisition. RESULTS: Of the 1158 FSWs, 950 were defined as LTFUs (LTFU rate: 29.69, 95 % CI: 27.85-31.62 per 100 person years [PYs]), and 33 experienced HIV seroconversions (cumulative incidence: 1.06, 95 % CI: 0.74-1.47 per 100 PYs). After adjustment, we found that FSWs who used drugs were less likely to be LTFU compared with non-drug users (adjust hazard ratio [AHR]= 0.62, 95 % CI: 0.51 0.76), though FSWs who used drug were associated with a higher risk of HIV acquisition (AHR = 3.06, 95 % CI: 1.49-6.30). Also, FSWs who always used condoms with clients in the previous month were associated with a higher risk of LTFU (AHR = 1.51, 95 % CI: 1.15-1.97), while they were negative associated with new HIV infection (AHR = 0.28, 95 % CI: 0.12-0.61). CONCLUSIONS: A high LTFU rate exists in the Kaiyuan FSW cohort study, and LTFU did not occur at random. Participants retained in the cohort tended to be at higher risk of HIV acquisition, which may result in an overestimate of the incidence of HIV infection from the Kaiyuan FSW cohort. PMID- 27686154 TI - Carrier Localization Effects in InGaN/GaN Multiple-Quantum-Wells LED Nanowires: Luminescence Quantum Efficiency Improvement and "Negative" Thermal Activation Energy. AB - Two-dimensional InGaN/GaN multiple-quantum-wells (MQW) LED structure was nanotextured into quasi-one-dimensional nanowires (NWs) with different average diameters with a combination approach of Ni nanoislands as mask + dry etching. Such nanotexturing bring out several appealing effects including deeper localization of carriers and significant improvement in quantum efficiency (e.g., from 4.76% of the planar MQW structure to 12.5% of the 160 nm MQW NWs) of light emission in the whole interested temperature range from 4 K to 300 K. With the aid of localized-state ensemble (LSE) luminescence model, the photoluminescence spectra of the samples are quantitatively interpreted in the entire temperature range. In terms of distinctive temperature dependence of photoluminescence from these samples, a concept of "negative" thermal activation energy is tentatively proposed for the MQW NWs samples. These findings could lead to a deeper insight into the physical nature of localization and luminescence mechanism of excitons in InGaN/GaN nanowires. PMID- 27686155 TI - Social Network Analysis Reveals Potential Fission-Fusion Behavior in a Shark. AB - Complex social networks and behaviors are difficult to observe for free-living marine species, especially those that move great distances. Using implanted acoustic transceivers to study the inter- and intraspecific interactions of sand tiger sharks Carcharias taurus, we observed group behavior that has historically been associated with higher order mammals. We found evidence strongly suggestive of fission-fusion behavior, or changes in group size and composition of sand tigers, related to five behavioral modes (summering, south migration, community bottleneck, dispersal, north migration). Our study shows sexually dimorphic behavior during migration, in addition to presenting evidence of a potential solitary phase for these typically gregarious sharks. Sand tigers spent up to 95 consecutive and 335 cumulative hours together, with the strongest relationships occurring between males. Species that exhibit fission-fusion group dynamics pose a particularly challenging issue for conservation and management because changes in group size and composition affect population estimates and amplify anthropogenic impacts. PMID- 27686153 TI - Inflammatory mediators in the development and progression of benign prostatic hyperplasia. AB - Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. Epidemiological data suggest a causal link between this condition and prostatic inflammation. The prostate is an immune-competent organ characterized by the presence of a complex immune system. Several stimuli, including infectious agents, urinary reflux, metabolic syndrome, the ageing process, and autoimmune response, have been described as triggers for the dysregulation of the prostatic immune system via different molecular pathways involving the development of inflammatory infiltrates. From a pathophysiological standpoint, subsequent tissue damage and chronic tissue healing could result in the development of BPH nodules. PMID- 27686156 TI - Mental health for nations. AB - Mental ill health is a universal phenomenon: that is, it is seen across all cultures and societies, even though the presentation may be culture-specific and affected by cultural norms and more. Governments have a moral and ethical duty to develop mental health services which are accessible, appropriate, and non discriminatory. Equity in funding mental health services is critical. As globally services and their quality vary dramatically, one should be proposing and agreeing on minimum standards of care. In this paper the basic components and minimum standards of care are described. It is imperative that services are non discriminatory. It is important that governments work with psychiatrists, other mental health professionals, and individuals with mental illness, their families, and carers to plan, develop, and deliver services with adequate funding. Employers and psychological first aid must also be remembered. Services must be geographically accessible. In this endeavour primary care services have a major role to play. Training and clinical decision-making must be part of the change in service delivery. It is imperative that every effort is made to keep the population mentally as well as physically healthy, and people who develop mental illness must have access to evidence-based treatment at the earliest possible opportunity. PMID- 27686158 TI - Discrimination and right to contract. PMID- 27686157 TI - Legal protection of the right to work: widening access to well-being through supportive workplaces. PMID- 27686159 TI - Economic development does not improve public mental health spending. AB - As a result of rapid globalization the Gross Domestic product of countries may have changed, but the gap between the very rich countries and poor countries has changed too, along with a change in social and economic strata within each society; although the rates of psychiatric disorders are affected by industrialization and urbanization, the financial pressures add yet another layer of burden. Global burden of disease due to mental illness is tremendously high and yet, in spite of pressures, there is no equity and increased discrimination related to mental illness. This paper presents some of the issues related to the economic state of the countries. In order to ensure that citizens receive the best treatments available it is important that socio-economic causes and gaps in treatment are identified and dealt with at national levels. PMID- 27686160 TI - Optimisation of a Naviglio-assisted extraction followed by determination of piperine content in Piper longum extracts. AB - Studies were made to increase the yield of piperine extraction using Naviglio Extractor(r) solid-liquid dynamic extractor (SLDE) from fruits of Piper longum. The effects of ratio w/v were investigated and optimised for the best method. The maximum yield of piperine (317.7 mg/g) from P. longum fruits was obtained in SLDE 1:50 ethanol extract. Extraction yields of piperine obtained from Soxhlet extraction, decotion (International Organization for Standardization) and conventional maceration extraction methods were found to be 233.7, 231.8 and 143.6 mg/g, respectively. The results of the present study indicated that Naviglio Extractor(r) is an effective technique for the extraction of piperine from long pepper. PMID- 27686162 TI - Hyaluronic Acid Stabilized Iodine-Containing Nanoparticles with Au Nanoshell Coating for X-ray CT Imaging and Photothermal Therapy of Tumors. AB - In recent years, considerable efforts have been made for the development of multifunctional nanoparticles with diagnosis and therapy functions. To achieve enhanced CT imaging and photothermal therapy on the tumor, we employed iodinated nanoparticles as template to construct Au nanoshell structure and demonstrated a facile but effective approach to synthesize biocompatible and well-dispersed multifunctional nanoparticles by coating iodinated nanoparticles with Au nanoshell and subsequent surface modification by hyaluronic acid. The resultant poly(2-methacryl(3-amide-2,4,6-triiodobenzoic acid))/polyethylenimine/Au nanoshell/hyaluronic acid (PMATIB/PEI/Au nanoshell/HA) nanoparticles had relatively high X-ray attenuation coefficient and photothermal efficiency. After intravenous injection into MCF-7 tumor-bearing mice, PMATIB/PEI/Au nanoshell/HA nanoparticles were efficiently accumulated in the tumor, remarkably enhanced the tumor CT imaging, and selectively ablated the tumor through the thermal treatment of lesions under the NIR irradiation. Thus, PMATIB/PEI/Au nanoshell/HA nanoparticles displayed a great potential for CT diagnosis and CT-guided, focused photothermal tumor therapy. PMID- 27686161 TI - Cerebrospinal fluid Presenilin-1 increases at asymptomatic stage in genetically determined Alzheimer's disease. AB - BACKGROUND: Presenilin-1 (PS1), the active component of the intramembrane gamma secretase complex, can be detected as soluble heteromeric aggregates in cerebrospinal fluid (CSF). The aim of this study was to examine the different soluble PS1 complexes in the lumbar CSF (CSF-PS1) of individuals with Alzheimer's disease (AD), particularly in both symptomatic and asymptomatic genetically determined AD, in order to evaluate their potential as early biomarkers. METHODS: Western blotting, differential centrifugation and co-immunoprecipitation served to determine and characterize CSF-PS1 complexes. We also monitored the assembly of soluble PS1 into complexes in a cell model, and the participation of Abeta in the dynamics and robustness of the stable PS1 complexes. RESULTS: There was an age-dependent increase in CSF-PS1 levels in cognitively normal controls, the different complexes represented in similar proportions. The total levels of CSF PS1, and in particular the proportion of the stable 100-150 kDa complexes, increased in subjects with autosomal dominant AD that carried PSEN1 mutations (eight symptomatic and six asymptomatic ADAD) and in Down syndrome individuals (ten demented and ten non-demented DS), compared with age-matched controls (n = 23), even prior to the appearance of symptoms of dementia. The proportion of stable CSF-PS1 complexes also increased in sporadic AD (n = 13) and mild cognitive impaired subjects (n = 12), relative to age-matched controls (n = 17). Co-immunoprecipitation demonstrated the association of Abeta oligomers with soluble PS1 complexes, particularly the stable complexes. CONCLUSIONS: Our data suggest that CSF-PS1 complexes may be useful as an early biomarker for AD, reflecting the pathology at asymptomatic state. PMID- 27686164 TI - Contribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson's disease. AB - INTRODUCTION: Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, and engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. METHOD: Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson's disease (PD) populations to what extent cognitive performance in several domains was explained by (a) any of these four environmental lifespan variables; (b) demographic and clinical variables (age, gender, depression score, and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. RESULTS: Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and (a) education, (b) leisure activities, and (c) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. CONCLUSIONS: Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and professional solicitation) are those that are the more strongly associated to late cognitive efficiency. PMID- 27686163 TI - Comparison of attitudes toward disability and people with disability among caregivers, the public, and people with disability: findings from a cross sectional survey. AB - BACKGROUND: A negative attitude toward disability is one of the potential barriers for people with disability (PWD) to achieve social equality. Although numerous studies have investigated attitudes toward disability, few have evaluated personal attitudes toward disability among PWD, and made comparisons with attitudes of healthy respondents. This study was to investigate and compare the attitudes of PWD, caregivers, and the public toward disability and PWD in China, to identify discrepancies in attitude among the three groupsand to examine potential influencing factors of attitude within each group. METHODS: A cross sectional study was conducted among 2912 PWD, 507 caregivers, and 354 members of the public in Guangzhou, China. Data were collected on participants' socio demographic information and personal attitudes toward disability using the Attitude to Disability Scale (ADS). ANOVA and ANCOVA were applied to compare the level of attitude among the three groups. Simple and multiple linear regression analyses were used to investigate the relationship between each background factor and attitude within each group. RESULTS: Over 90 % of caregivers were PWD's family members. After controlling the socio-demographic characteristics, caregivers had the lowest total scores of ADS (caregivers: 47.7; PWD: 52.3; the public: 50.5). Caregivers who had taken care of PWD for longer durations of time had a more negative attitude toward disability. In contrast, PWD who had been disabled for longer times had a more positive attitude toward disability. CONCLUSIONS: The current national social security system of China does not adequately support PWD's family-member caregivers who may need assistance coping with their life with PWDs. More research is needed, and the development of a new health-care model for PWD is warranted. PMID- 27686165 TI - Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. AB - BACKGROUND: The association of thyroid function with risk of type 2 diabetes remains elusive. We aimed to investigate the association of thyroid function with incident diabetes and progression from prediabetes to diabetes in a population based prospective cohort study. METHODS: We included 8452 participants (mean age 65 years) with thyroid function measurement, defined by thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and longitudinal assessment of diabetes incidence. Cox-models were used to investigate the association of TSH and FT4 with diabetes and progression from prediabetes to diabetes. Multivariable models were adjusted for age, sex, high-density lipoprotein cholesterol, and glucose at baseline, amongst others. RESULTS: During a mean follow-up of 7.9 years, 798 diabetes cases occurred. Higher TSH levels were associated with a higher diabetes risk (hazard ratio [HR] 1.13; 95 % confidence interval [CI], 1.08-1.18, per logTSH), even within the reference range of thyroid function (HR 1.24; 95 % CI, 1.06-1.45). Higher FT4 levels were associated with a lower diabetes risk amongst all participants (HR 0.96; 95 % CI, 0.93-0.99, per 1 pmol/L) and in participants within the reference range of thyroid function (HR 0.96; 95 % CI, 0.92-0.99). The risk of progression from prediabetes to diabetes was higher with low-normal thyroid function (HR 1.32; 95 % CI, 1.06-1.64 for TSH and HR 0.91; 95 % CI, 0.86 0.97 for FT4). Absolute risk of developing diabetes type 2 in participants with prediabetes decreased from 35 % to almost 15 % with higher FT4 levels within the normal range. CONCLUSIONS: Low and low-normal thyroid function are risk factors for incident diabetes, especially in individuals with prediabetes. Future studies should investigate whether screening for and treatment of (subclinical) hypothyroidism is beneficial in subjects at risk of developing diabetes. PMID- 27686166 TI - Acute effects of high-intensity intermittent training on kinematics and foot strike patterns in endurance runners. AB - The main purpose of this study was to evaluate running kinematic characteristics and foot strike patterns (FSP) during early and late stages of actual and common high-intensity intermittent training (HIIT): 5 * 2000 m with 120-s recovery between runs. Thirteen healthy, elite, highly trained male endurance runners participated in this study. They each had a personal record in the half-marathon of 70 +/- 2.24 min, and each had a minimum experience of 4 years of training and competition. Heart rate (HR) and rate of perceived exertion (RPE) were monitored during HIIT. High levels of exhaustion were reached by the athletes during HIIT (HRpeak: 174.30 bpm; RPE: 17.23). There was a significant increase of HRpeak and RPE during HIIT; nevertheless, time for each run remained unchanged. A within protocol paired t-test (first vs. last run) revealed no significant changes (P >= 0.05) in kinematics variables and FSP variables during HIIT. There were no substantial changes on kinematics and FSP characteristics in endurance runners after fatigue induced by a HIIT. Only the minimum ankle alignment showed a significant change. The author suggests that these results might be due to both the high athletic level of participants and their experience in HIIT. PMID- 27686167 TI - Estimating audiometric thresholds using simultaneous acquisition of ASSR and ABR from QASSR in patients with sensorineural hearing loss. AB - OBJECTIVES: To evaluate the accuracy with which the innovative QASSR method predicts behavioral thresholds in adult patients with sensorineural hearing loss. DESIGN: Subjects were tested at four carrier frequencies (500, 1000, 2000, and 4000 Hz).The resulting QASSR recordings were analyzed for thresholds and magnitude/phase characteristics. Tone-burst ABR was recovered from QASSR signal using CLAD method and analyzed in the time domain. The electrophysiological estimates were compared to hearing thresholds determined behaviorally. STUDY SAMPLE: Sixteen ears of nine volunteer subjects recruited from a clinical population. RESULTS: All mean threshold estimates differed less than 3 dB for QASSR and less than 5 dB for ABR at 1000, 2000 and 4000Hz (carrier or pure-tone test frequencies). The largest differences were observed for both at 500 Hz (5.63 and 11.56 dB respectively).The audiometric configurations of QASSR and ABR estimates followed those of the respective behaviorally determined configurations across ears tested. CONCLUSIONS: QASSR method merges two dissimilar stimulation techniques, transient and steady-state, to create a hybrid stimulation-and analysis paradigm that seems to improve the overall performance of the electrophysiological threshold estimation. The unique feature of the QASSR technique is the additional information afforded by the transient ABR, recovered from the same recording. The QASSR thus holds promise to be a very useful tool for practical clinical applications. PMID- 27686168 TI - The safety and efficacy of high versus low vancomycin trough levels in the treatment of patients with infections caused by methicillin-resistant Staphylococcus aureus: a meta-analysis. AB - BACKGROUND: Recent guidelines have recommended vancomycin trough levels of 15-20 mg/L for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, high trough levels may increase risk of nephrotoxicity and mortality, and high vancomycin trough levels have not been well studied. This study was designed to combine safety and efficacy results from independent studies and to compare between high and low vancomycin trough levels in the treatment of MRSA-infected patients using meta-analysis. METHODS: From 19 eligible studies, 9 studies were included in meta-analysis to compare clinical success between high and low vancomycin trough levels, while 10 and 11 studies met criteria for comparing trough levels and nephrotoxicity and trough levels and mortality, respectively. The PubMed/Medline, Web of Science, and Scopus databases, and hand searching were used to identify eligible studies dated up to March 2016. Of 2344 subjects with MRSA infection, 1036 were assigned to trough levels >=15 mg/L and 1308 to trough levels <15 mg/L. RESULTS: High vancomycin trough levels were found to be associated with risk of nephrotoxicity (odds ratio [OR] 2.14, 95 % confidence interval [CI] 1.42-3.23 and adjusted OR 3.33, 95 % CI 1.91-5.79). There was no evidence of difference between high and low vancomycin trough levels for mortality (OR; 1.09; 95 % CI 0.75-1.60) or clinical success (OR 1.07; 95 % CI 0.68-1.68). CONCLUSION: In this study, high vancomycin trough levels were identified as an independent factor associated with risk of nephrotoxicity in MRSA-infected patients. Association between vancomycin trough levels and both adverse effects and clinical outcomes requires further study. PMID- 27686169 TI - Laboratory Investigation of Myeloproliferative Neoplasms (MPNs): Recommendations of the Canadian Mpn Group. AB - OBJECTIVES: To standardize diagnostic investigations for myeloproliferative neoplasms (MPNs) to increase homogeneity in patient care and to streamline diagnostic approaches in the most efficient and cost-effective manner. METHODS: The development of Canadian expert consensus recommendations for the diagnosis of MPNs began with a review of the following: clinical evidence, daily practice, existing treatment guidelines, and availability of diagnostic tools. Each group member was assigned a specific topic, which they discussed with the entire group during several consensus meetings. RESULTS: This document provides the Canadian MPN group's recommendations, proposed diagnostic algorithms, and background evidence upon which decisions were made. CONCLUSIONS: Standardization of diagnostic investigations will increase homogeneity in patient care and provide a foundation for future clinical research in this rapidly evolving therapeutic area. Streamlining diagnostic approaches in the most efficient and cost-effective manner will also result in significant cost saving for the health care system. PMID- 27686170 TI - CAL2 Immunohistochemical Staining Accurately Identifies CALR Mutations in Myeloproliferative Neoplasms. AB - OBJECTIVES: Mutations in CALR (calreticulin) have been discovered in 50% to 80% of JAK2 (Janus kinase 2) and MPL (myeloproliferative leukemia protein) wild-type patients with Philadelphia-negative myeloproliferative neoplasm (MPNs). We evaluate the performance of a monoclonal antibody for immunohistochemical detection of CALR mutations. METHODS: A computerized archival search was performed for cases of non-chronic myeloid leukemia (CML) MPNs with available CALR and JAK2 V617F mutational analysis data. Bone marrow biopsy specimens were stained with monoclonal antibody CAL2, and the percentage of stained megakaryocytes was calculated. In select cases, double immunofluorescence staining was done with CAL2 and each of the following: CD61, myeloperoxidase, CD34, and glycophorin A. RESULTS: We studied 38 bone marrow biopsy specimens of non-CML MPNs (primary myelofibrosis, n = 21; essential thrombocythemia, n = 15; and n = 2 post-polycythemia vera myelofibrosis) from 31 patients. All eight bone marrow biopsy specimens from patients with mutant CALR showed strong cytoplasmic staining of the megakaryocytes (83.5%; range, 50%-98%; median, 87%) with the CAL2 antibody. Double immunofluorescence staining of the small mononuclear cells seen in CALR mutant cases revealed them to be myeloid blasts. CONCLUSIONS: Immunohistochemistry in routinely processed bone marrow biopsy specimens for mutated CALR is feasible and accurately identifies mutated cases, including rare cases with additional driver mutations. PMID- 27686171 TI - Detection of CALR Mutation in Clonal and Nonclonal Hematologic Diseases Using Fragment Analysis and Next-Generation Sequencing. AB - OBJECTIVES: To describe three methods used to screen for frameshift mutations in exon 9 of the CALR gene. METHODS: Genomic DNA from 47 patients was extracted from peripheral blood and bone marrow using the EZ1 DNA Blood Kit (Qiagen, Valencia, CA) and quantified by the Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen, San Diego, CA). After clinical history, cytogenetics, and molecular tests, patients were diagnosed with either clonal or nonclonal hematologic diseases. CALR screening was primarily performed using fragment analysis polymerase chain reaction, then next-generation sequencing and Sanger sequencing. RESULTS: Among the 18 patients diagnosed with clonal diseases, one had acute myeloid leukemia (positive for trisomy 8), and 17 had myeloproliferative neoplasms (MPNs), including chronic myeloid leukemia (CML), essential thrombocythemia (ET), primary myelofibrosis (PMF), and polycythemia vera (PV). Patients with CML were positive for the BCR-ABL1 fusion. Ten patients were positive for JAK2 (PMF, n = 1; ET, n = 2; PV, n = 7), and three were CALR positive (ET, n = 1; PMF, n = 2). Patients diagnosed with a nonclonal disease were negative for JAK2, BCR-ABL, and CALR mutations. CONCLUSIONS: Screening for CALR mutations is essential in BCR-ABL negative MPNs since it not only provides valuable diagnostic and prognostic information but also identifies potential treatment targets. Since this study describes the importance of screening for known and novel biomarkers, we described in detail three methods that could be easily integrated into a clinical laboratory. PMID- 27686172 TI - Significant Reduction in Preanalytical Errors for Nonphlebotomy Blood Draws After Implementation of a Novel Integrated Specimen Collection Module. AB - OBJECTIVES: Most preanalytical errors at our institution occur during nonphlebotomy blood draws. We implemented an electronic health record (EHR), interfaced the EHR to the laboratory information system, and designed a new specimen collection module. We studied the effects of the new system on nonphlebotomy preanalytical errors. METHODS: We used an electronic database of preanalytical errors and calculated the number and type of the most common errors in the emergency department (ED) and inpatient nursing for 3-month periods before (August-October 2014) and after (August-October 2015) implementation. The level of staff compliance with the new system was also assessed. RESULTS: The average monthly preanalytical errors decreased significantly from 7.95 to 1.45 per 1,000 specimens in the ED (P < 0001) and 11.75 to 3.25 per 1,000 specimens in inpatient nursing (P < 0001). The rate of decrease was similar for mislabeled, unlabeled, wrong specimen received and no specimen received errors. Most residual errors (80% in the ED and 67% in inpatient nursing) occurred when providers did not use the new system as designed. CONCLUSIONS: Implementation of a customized specimen collection module led to a significant reduction in preanalytical errors. Improved compliance with the system may lead to further reductions in error rates. PMID- 27686174 TI - Clinical Action Curves: Measuring the Magnitude of Physician Response to Abnormal Laboratory Results. AB - OBJECTIVES: While reference limits are foundational to interpreting clinical laboratory tests, they may not correspond to the actual values triggering clinical response. We propose to measure this using clinical action curves, which plot test values against an indicator of clinical action. METHODS: We selected repeat test ordering as a quantifiable, objective, useful measure that is readily calculable using available laboratory data. Using all results in Calgary in 2010 2011 for eight analytes, clinical action curves for each analyte were plotted as the relationship between index test value and retesting hazard, modeled using Cox proportional hazards with restricted cubic splines. Clinical action limits were defined where retesting hazard rose 38% above baseline (25%-50% considered). RESULTS: In general, clinical action increased before the reference limits, and clinical action limits were narrower than reference limits. However, some reference limits showed no increased clinical action and may thus be ignored in practice. CONCLUSIONS: Clinical action curves and limits provide practical, objective tools for describing physician responses to test values. Results suggest that many normal results are treated as abnormal and vice versa; such discrepancies require further scrutiny and ultimately reconciliation via altered reference ranges or altered practice patterns. PMID- 27686173 TI - Effect of On-Site Support on Laboratory Practice for Human Immunodeficiency Virus, Tuberculosis, and Malaria Testing. AB - OBJECTIVES: To evaluate the effect of on-site support in improving human immunodeficiency virus (HIV) rapid testing, tuberculosis (TB) sputum microscopy, and malaria microscopy among laboratory staff in a low-resource setting. METHODS: This cluster randomized trial was conducted at 36 health facilities in Uganda. From April to December 2010, laboratory staff at 18 facilities participated in monthly on-site visits, and 18 served as control facilities. After intervention, 128 laboratory staff were observed performing 587 laboratory tests across three diseases: HIV rapid testing, TB sputum microscopy, and malaria microscopy. Outcomes were the proportion of laboratory procedures correctly completed for the three laboratory tests. RESULTS: Laboratory staff in the intervention arm performed significantly better than the control arm in correctly completing laboratory procedures for all three laboratory tests, with an adjusted relative risk (95% confidence interval) of 1.18 (1.10-1.26) for HIV rapid testing, 1.29 (1.21-1.40) for TB sputum microscopy, and 1.19 (1.11-1.27) for malaria microscopy. CONCLUSIONS: On-site support significantly improved laboratory practices in conducting HIV rapid testing, TB sputum microscopy, and malaria microscopy. It could be an effective method for improving laboratory practice, without taking limited laboratory staff away from health facilities for training. PMID- 27686175 TI - Spindle Cell Lipomas Arising at Atypical Locations. AB - OBJECTIVES: Spindle cell lipomas (SCLs) are benign lipomatous neoplasms that classically arise in the posterior neck, upper back, and shoulders of older male patients. We sought to characterize the occurrence of this entity at nonclassic sites. METHODS: All cases of SCL arising at atypical sites were retrieved from our archives. RESULTS: Of 439 total cases of SCL, 57 arose at atypical locations in 32 men and 25 women (age range, 27-79 years). The tumor sites included leg (n = 23), buttock/perineum/inguinal (n = 10), forearm (n = 9), finger (n = 9), foot (n = 2), toe (n = 2), hand (n = 1), and flank (n = 1). CD34 was positive staining in all cases tested (52/52), while desmin was negative in most tumors (48/50). Thirty-eight of 38 cases tested exhibited loss of Rb expression. No cases showed CPM/MDM2 amplification (0/48). No local recurrences have been reported (n = 39). CONCLUSIONS: SCLs may arise in the trunk, lower extremities, and distal upper extremities. While most SCLs arising in classic sites occur in male patients, there is a relatively equal sex distribution in tumors at atypical sites. Pathologists should be aware that SCLs arise at atypical locations to avoid misclassification as other lipomatous neoplasms, including atypical lipomatous tumor. PMID- 27686176 TI - Stromal PD-L1 Expression Is Associated With Better Disease-Free Survival in Triple-Negative Breast Cancer. AB - OBJECTIVES: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and there is no approved targeted therapy. We studied the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in TNBC. METHODS: Full-face sections from 136 TNBC cases without neoadjuvant therapy between 2004 and 2013 were stained and evaluated for immune cell PD-1 staining and stromal or tumoral PD-L1 staining using the H-score (staining percentage * intensity). Nottingham histologic grade, lymphovascular invasion (LVI), mitotic count, and tumor-infiltrating lymphocytes (TILs) were evaluated. Tumor size, lymph node status, Ki-67 score, metastasis, overall survival (OS), and disease free survival (DFS) were retrieved from medical records. RESULTS: Of the 136 TNBC cases, 69 (51%) had any PD-L1 staining and 35 (26%) had PD-L1 staining with an H score of 5 or more; 117 (86%) had any PD-1 staining and 68 (50%) had PD-1 staining with an H-score of 5 or more. Tumor size and LVI were significantly associated with worse OS and DFS, and TILs and LVI were significantly associated with metastasis in univariate analysis. Stromal PD-L1 expression was significantly associated with better DFS in multivariate analysis. PD-1 expression was not associated with DFS, OS, or metastasis. CONCLUSIONS: PD-L1 expression is seen in a high proportion of TNBCs and associated with better DFS. PMID- 27686178 TI - Deciphering molecular aspects of interaction between anticancer drug mitoxantrone and tRNA. AB - Mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10 anthracenedione) is a synthetically designed antineoplastic agent and structurally similar to classical anthracyclines. It is widely used as a potent chemotherapeutic component against various kinds of cancer and possesses lesser cardio-toxic effects with respect to naturally occurring anthracyclines. In the present study, we have investigated the binding features of mitoxantrone-tRNA complexation at physiological pH using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, circular dichroism (CD) spectroscopy, isothermal titration calorimetry, and UV-visible absorption spectroscopic techniques. FTIR analysis reveals that mitoxantrone interacts mainly with heterocyclic base residues of tRNA along with slight external binding with phosphate-sugar backbone. In particular, mitoxantrone binds at uracil (C=O) and adenine (C=N) sites of biomolecule (tRNA). CD spectroscopic results suggest that there is no major conformational transition in native A-form of tRNA upon mitoxantrone-tRNA adductation except an intensification in the secondary structure of tRNA is evident. The association constant calculated for mitoxantrone-tRNA association is found to be 1.27 * 105 M-1 indicating moderate to strong binding affinity of drug with tRNA. Thermodynamically, mitoxantrone tRNA interaction is an enthalpy-driven exothermic reaction. Investigation into drug-tRNA interaction can play an essential role in the rational development of RNA targeting chemotherapeutic agents, which also delineate the structural functional relationship between drug and its target at molecular level. PMID- 27686177 TI - Phosphohistone-H3 Proliferation Index Is Superior to Mitotic Index and MIB-1 Expression as a Predictor of Recurrence in Human Meningiomas. AB - OBJECTIVES: This study investigated the prognostic value of the phosphohistone-H3 (PHH3) proliferation index (PI) in human meningiomas and compared the reliability with the conventional mitotic index and MIB-1 biomarker. METHODS: Proliferative activity was determined in 160 patients by standardized immunohistochemistry on tissue microarrays and related to recurrence. RESULTS: All three proliferation assessment methods were significantly associated with World Health Organization grade. The optimal cutoff values for recurrence prediction were 3% for the MIB-1 PI and 0.5% for the PHH3 PI. Increased PHH3 PI was significantly associated with recurrence-free survival in univariate Cox proportional hazards regression analysis (P = .011) and remained an independent predictor in multivariate analysis (P = .005). Mitotic index and MIB-1 PI did not reach statistical significance. CONCLUSIONS: PHH3 immunostaining allowed for the easiest, fastest, and most objective assessment of proliferation and proved to be the most accurate and reliable method for predicting recurrence in patients resected for meningiomas. PMID- 27686180 TI - Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting? AB - OBJECTIVES: A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice. METHODS: Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD4 nadir on the incidence of active TB was evaluated. RESULTS: Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/MUl. Thirty six percent of incident TB occurred within 14 days after HIV diagnosis. CONCLUSION: A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir. PMID- 27686179 TI - Pneumococcal infections in elderly patients attending hospital since PCV-13 authorization in Spain. AB - OBJECTIVES: To study the characteristics and outcomes of pneumococcal infections in patients aged >=65 years since the authorization of the 13-valent pneumococcal conjugate vaccine (PCV-13) in Spain. METHODS: All pneumococcal pneumonias, empyemas or primary bacteraemias treated at two hospitals in Majorca from 2010 to 2015 were included. Clinical variables, serotypes, and antibiotic susceptibility were collected. RESULTS: Two hundred and forty-nine pneumonias, 11 primary bacteraemias, and 2 empyemas in 243 patients were studied; 181 (69.1%) men, median age 76 years (range: 66-99). Seven (2.6%) were pneumococcal-vaccinated. Bacteraemia was present in 127 (61.9%) cases and related to a higher severity, p= 0.02, and not having chronic lung disease, p = 0.002. Ninety-seven (37%) episodes involved complications and 30 (11.5%) patients died. Mortality was related with the presence of complications at admission, p < 0.001. Only septic shock was more frequent in patients >=65 years during the period 2010-2015 compared to the period 2006-2010: 38 of 262 (14.5%) vs. 17 of 212 (8%), p = 0.02. Most infections (57.6%) were due to PCV-13 serotypes but were not related to a worse prognosis. The proportion of PCV-13 serotypes tended to decrease from 61% (non-invasive) and 80% (invasive) in 2010-2011 to 33% and 47% in 2014-2015. The antibiotic susceptibility remained stable. CONCLUSIONS: Rates of pneumococcal vaccination in elderly patients with pneumococcal infections were very low. Except for septic shock, the main outcome variables (including mortality) were similar to the ones observed in the period preceding PCV-13 authorization. PCV-13 serotypes were responsible for most infections although they showed a decreasing trend. PMID- 27686181 TI - Risk factors of sleep disorder after stroke: a meta-analysis. AB - OBJECTIVE: The study aimed to evaluate potential risk factors of sleep disorder in stroke patients by conducting a meta-analysis. METHODS: Relevant articles were searched in PubMed, Medline, Springer, Elsevier, Science Direct, Cochrane Library, and Google scholar database up to May 2014. The effect size of risk factors, including gender, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol use, previous stroke, chronic obstructive pulmonary disease (COPD), and habitual snoring were measured by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The heterogeneity of effect size across studies was evaluated by applying Cochran's Q-statistic and the I2 statistic. In addition, Egger's linear regression test was used to evaluate the publication bias. RESULTS: A total of 8 studies, involving 1381 stroke patients (578 patients with sleep disorder, and 803 patients without sleep disorder) were suitable for this meta-analysis. Pooled results showed significant association of sleep disorder risk in stoke patients with diabetes mellitus (OR = 1.42, 95% CI = 1.09 1.85), alcohol use (OR = 1.59, 95% CI = 1.19-2.12) and habitual snoring (OR = 14.77, 95% CI = 5.52-39.53). No significant association was found between risk of sleep disorder in stoke patients and other factors. Furthermore, heterogeneity was just presented among studies involving gender, hypertension and smoking. Egger's linear regression test showed no statistical publication bias. CONCLUSION: Diabetes mellitus, alcohol use, and habitual snoring are associated with a significantly increased risk of sleep disorder in stroke patients. HIGHLIGHTS: (1) Eight studies containing 1381 patients are included in this meta analysis. (2) Diabetes mellitus was associated with sleep disorder in stroke patients. (3) Alcohol use could increase the risk of sleep disorder in stroke patients. (4) Habitual snoring was obviously associated with sleep disorder in stroke patients. PMID- 27686183 TI - Reducing transfers of psychiatric inpatients to emergency rooms of general hospitals in Singapore: a clinical practice improvement project. AB - OBJECTIVE: Patients admitted to a psychiatric hospital commonly suffer from comorbid medical problems which sometimes require urgent medical attention. Twenty-two percent of emergency medical transfers from the Institute of Mental Health (IMH) to the emergency rooms of general hospitals were preventable and could be managed at IMH itself. We undertook a quality improvement project to understand the reasons behind such preventable referrals and implemented changes to address this. METHODS: Using the model for improvement, we deconstructed our processes and analysed root causes for such preventable referrals. Thereafter changes were implemented with Plan-Do-Study-Act (PDSA) cycles to analyse their outcomes. RESULTS: During the 6-month study period, we achieved a 100% reduction in preventable referrals through strategies aimed at reducing pressure on our on call physicians in the making of medical decisions, maximising usage of our medical resources, constant education and raising awareness of this issue. CONCLUSIONS: Reducing preventable transfer of inpatients from a psychiatric hospital to the emergency departments of general hospitals is a worthwhile endeavour. Such initiatives optimise use of healthcare resources, improve patient care and increase satisfaction. PMID- 27686182 TI - Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women. AB - Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine raises controversies on immunogenicity and possible antibody interference. We performed an experimental, double-blind, parallel group controlled clinical trial to evaluate the safety and immunogenicity of the Tdap vaccine in 204 pregnant women and their children and to determine its interference in antibody production. Pregnant women 18 to 38 y of age with 12 to 24 weeks gestation, a low obstetric risk, and without serious disease were randomly selected. The experimental group received 0.5 mL IM of Tdap and the control group normal saline. Six blood samples were drawn before and after solution application, and from the umbilical cord of the infants and at 2, 4, and 6 months of age. Pertactin and Pertussis toxin antibodies and possible interference of maternal antibodies with the vaccine were determined. In the experimental group, antibodies against Bordetella pertussis pertactin (anti-PRN) (112 E/mL 95% CI 89.9-139.9) and antibodies against pertussis toxin (anti-PT) (24.0 E/mL, 95% CI 18.3-31.4) were elevated in the mother before vaccination. These were higher in the umbilical cord and descended in the infant at 2 months (71.4 (95% CI 56.8-89.7 and 10.9; 95% CI 8.7-13.7, respectively). Anti-PT showed a delay in production. Tdap safety was confirmed with only mild local pain at 24 and 48 hours. Anti-PRN and anti-PT antibodies in the infant descend at 2 months of age. There is a delay in anti-PT in children of immunized mothers. Further studies are needed to elucidate its clinical significance. PMID- 27686184 TI - OTULIN deficiency causes auto-inflammatory syndrome. AB - Ubiquitin chains assembled via the N-terminal methionine (Met1 or linear ubiquitin), conjugated by the linear ubiquitin chain assembly complex (LUBAC), participate in NF-kappaBeta-dependent inflammatory signaling and immune responses. A recent report in Cell finds that OTULIN, a deubiquitinase that selectively cleaves Met1-linked ubiquitin chains, is essential for restraining inflammation in vivo. PMID- 27686185 TI - Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission-fusion balance within mitochondrial networks. AB - Mitochondria form interconnected networks that dynamically remodel in response to cellular needs. Using live-cell imaging, we investigate the role of the actin cytoskeleton in regulating mitochondrial fission and fusion. We identify cycling of actin filaments onto and off of subsets of cellular mitochondria. The association of actin filaments with mitochondrial subpopulations is transient; actin quickly disassembles, then reassembles around a distinct subpopulation, efficiently cycling through all cellular mitochondria within 14 min. The focal assembly of actin induces local, Drp1-dependent fragmentation of the mitochondrial network. On actin disassembly, fragmented mitochondria undergo rapid fusion, leading to regional recovery of the tubular mitochondrial network. Cycling requires dynamic actin polymerization and is blocked by inhibitors of both Arp2/3 and formins. We propose that cyclic assembly of actin onto mitochondria modulates the fission/fusion balance, promotes network remodelling and content mixing, and thus may serve as an essential mechanism regulating mitochondrial network homeostasis. PMID- 27686186 TI - On the boundaries of ethics. PMID- 27686187 TI - [Ten years after the Sudbo-affair]. PMID- 27686188 TI - Predictive testing should be in the child's best interests. PMID- 27686189 TI - [Not Available]. PMID- 27686191 TI - [Not Available]. PMID- 27686190 TI - [Not Available].